PMID- 8978136
TI  - [Treatment of abdominal aortic aneurysm by application of a Corvita
      endoprosthesis. Medium-term results of a feasibility study].
AB  - Despite improvements in surgical techniques, progress in anesthesia and
      hemodynamic control, the risk of fatal outcome in the standard surgical technique
      for aneurysms of the abdominal aorta remains at about 5 to 6% due to associated
      coronary and pulmonary lesions. Surgical access to the aneurysm may also be
      hindered in patients with a past history of multiple abdominal operations. In
      collaboration with the Corvita company, we developed a modular endoprosthesis for
      endoluminal treatment of AAA and report the results of a feasibility study.

PMID- 8978137
TI  - [Surgically treated severe acute inflammatory colitis. Immediate results and long
      term outcome].
AB  - The goal of this study was to analyse the management and the long-term evolution
      of 40 patients surgically treated for acute colitis (AC) during a 10 year period.
      PATIENTS AND METHODS: From June 1985 to June 1995, 40 patients (22 males and 18
      females, mean age: 33,5 y.o.) have been consecutively operated on for AC.
      Assessment of severity was based on clinico-biological, endoscopic and
      radiological criterias: AC was complicated in 3, failing to respond to medical
      therapy in 9, resisting to medical therapy in 28. Sub-total colectomy (STC) with
      ileostomy and sigmoidostomy was the most frequently performed procedure (27 cases
      68%). RESULTS: 1) The preoperative diagnosis of colitis was modified 6 times
      (15%) after histological assessment of the specimen: the final diagnosis was
      ulcerative colitis, indeterminate colitis and Crohn colitis respectively in 36
      (90%), 2, and 2 cases. The established diagnosis had to be modified 4 times
      during follow-up. 2) Postoperative complications occurred in 5 after STC (18%)
      and in 4 in the other procedures (31%), without mortality. 3) After a mean follow
      up of 55 +/- 10 months of the all series, 7 patients (17,5%) had a stoma: 2 had
      ileo-anal anastomosis taken down and 2 returned to ileostomy for Crohn disease, 1
      patient with protected ileo-rectal anastomosis stayed with an ileostomy, 1
      patient refused ileo-anal anastomosis, and 1 with imperforate anus had terminal
      ileostomy. Respectively 25, 6 and 2 patients had a functional ileo-anal, ileo
      rectal, and colo-rectal anastomosis and experienced good to excellent digestive
      comfort in 85% of the cases.

PMID- 8978138
TI  - [Palliative treatment of rectal cancer by the trans-anal approach using a
      urologic prostatectomy device].
AB  - Palliative treatment for patients with rectal carcinoma affect more than 10% of
      the 8000 cases diagnosed each year in France. Twenty-four patients underwent
      endoscopic trans-anal resection using a urological resectoscope. The morbidity
      rate was 18,5% and there were no postoperative deaths. The median hospital stay
      for the procedure alone was 4 days. Good palliation was obtained in 89% of cases.
      This simple, minimally invasive and economic method should join palliative
      treatment for patients with rectal carcinoma beside laser destruction and
      external beam radiotherapy.

PMID- 8978139
TI  - [Evaluation of a new technique of extracorporeal perfusion of the swine liver on
      a swine-primate model].
AB  - With the increasing success of liver transplantation there is an urgent need for
      developing an artificial liver support system to be used in patients with liver
      failure. An extracorporeal porcine liver perfusion machine was successfully
      tested in animals with experimental liver failure. Livers were flushed, removed
      from 35 kg pigs and placed in a heated sterile cassette. The portal vein and the
      hepatic artery of the graft were connected to the arterial system of the animals.
      The perfusion pressure of the hepatic artery was regulated via a pressure-flow
      computerized feed-back device. The venous flow was reinfused from the hepatic
      veins of the graft to the jugular vein of the animals. The experimental work
      consisted in two steps: 1. evaluation of clinical and biological consequences of
      liver perfusion in healthy animals (Group A = pigs, n = 3; group B = primates, n
      = 3); 2. evaluation of the efficiency of the liver perfusion in animals with
      ischemic liver failure (Groupe D = pigs, n = 6). The control group (Group C =
      pigs, n = 7) consisted of pigs with ischemic liver failure without hepatic
      support. No major clinical or biological adverse effects are reported in groups A
      and B excepted a thrombocytmia and a marked increase in serum transaminases
      levels in group B. Liver function as assessed by the bile flow was good in both
      groups. Comatose pigs with ischemic hepatic failure (group D) recovered a
      subnormal neurological status in five out of six cases. Serum ammoniemia level
      were significantly decreased (from 1076 +/- 163 to 255 +/- 32 umol/l). A decrease
      in serum bilirubine levels and an improvement in the coagulation profile were
      observed in the perfused animals. Pigs and primates tolerated the perfusion
      procedure well and beneficial effects were observed in perfused pigs with
      experimental liver failure.

PMID- 8978140
TI  - [Mechanical system of left ventricle cannulation: control of tightness by
      experimental left ventricular assistance].
AB  - We have designed a mechanical device for left ventricular apex cannulation
      (SCAV). It will be used to implant a ventricular connection for a skeletal muscle
      ventricle placed in apicoaortic configuration without cardio-pulmonary bypass.
      The aim of this study was to assess the tightness of the ventricular connection
      at 48 hours. We used a left ventricular assist device (Biomedicus centrifugal
      pump) placed between the apex of the left ventricle and the descending thoracic
      aorta on 10 female sheep. The ventricular connection between the apex of the left
      ventricle and the Biomedicus was carried out with the SCAV and without cardio
      pulmonary bypass. The intra-operative mortality was 10% (1 sheep) due to
      ventricular fibrillation. Three sheep died early in the run of the ventricular
      assistance due to technical assistance problems not related to the SCAV. The full
      ventricular assistance could be managed in 6 sheep through 32 h 30 (range from 15
      to 46 h). No death occurred in these 9 sheep due to cardiac hemorrage or
      tamponade. The average apical bleeding in the pericardial drain was 157 ml (range
      from 20 to 270 ml). The tightness of the ventricular connection was proved by
      this study. The SCAV may be suitable for apical implantation of a skeletal muscle
      ventricle in sheep.

PMID- 8978141
TI  - [Genetic control of humoral immune response to xenografts. A monoclonal antibody
      that causes the hyperacute rejection of cardiac xenografts uses the genes in a
      native form].
AB  - The early phases of the rejection of xenografts exchanged between closely-related
      species are dominated by a vigorous humoral immune response. We have recently
      used a linkermediated polymerase chain reaction to generate Ig heavy and light
      chain specific cDNA libraries to examine the Ig gene control of a prototypic IgM
      monoclonal antibody, HAR-1, that causes the hyperacute rejection of hamster
      xenografts. Recombinant clones from the library were screened directly from
      bacterial colonies by PCR and the nucleic acid sequences of the clones
      established. Our results demonstrate that the HAR-1 hybridoma is encoded by Ig VH
      and JH genes in a germline configuration. Comparison of the cDNA sequence for
      HAR1-VH with the germline equivalent of the gene isolated from newborn LEW liver
      (provisionally designated VH1.1) showed that the two VH sequences share a nucleic
      acid identity of 99,3%. Similarly, the HAR-1 monoclonal uses a Ig JH gene that is
      98,2% identical with the JH1 nucleic acid sequence available in the GenBank. The
      use of Ig VH and JH genes in a germline configuration is similar to that seen
      with polyreactive natural antibodies to infectious agents and autoantibodies.
      These humoral responses are thought to be the results of the stimulation of a T
      cell-independent subset of B cells, the B-1a/B-1b subset, that are responsible
      for producing antibodies that serve as a primitive humoral (natural antibody)
      defense mechanism against infectious diseases. Our results suggest that the
      humoral component of the rejection of xenografts in the hamster-to-rat model may
      represent the stimulation of this type of B cell antibody response by xenogeneic
      target antigens that share antigenic epitopes with bacteria and other infectious
      agents.

PMID- 8978142
TI  - [Evaluations of protein p53 overexpression in cancer of the bladder: prognostic
      value].
AB  - Management of Transitional Cell Carcinoma (TCC) of the bladder depends on
      clinicopathological parameters at initial presentation. These criteria are
      insufficient predictors because of tumor heteterogeneity. Progress in tumor
      biology suggest that molecular markers may be used to dismember bladder cancer
      according to their biological behavior. Evidences have accumulated that cancer
      result from accumulation of molecular defect specially on tumor suppressor genes.
      In this respect we studied by mean of immunohistochemistry the prognostic value
      of p53 nuclear overexpression using monoclonal antibody P1801. The study was
      performed on 114 TTC and 13 normal bladders. Nuclear straining was quantified
      using an eye piece reticule at magnification 400x. Scoring was determined
      counting 500 nuclei in 3 to 5 arbitrary fields. Results between stage, grade and
      percentage of stained nuclei are as follow: TA 0,92-T1 0,144-T2 0,354-T4 0,622-G1
      0,105-G2 0,212-G3 0,406. Comparison of mean nuclear straining between group with
      and without progression indicates a threshold of 16% for p53 nuclear
      overexpression. Using this limit there is a significant progression free survival
      rate for the all group (p < 0,0001) and for the group of superficial tumors (p =
      0,0007). Multivariate analysis using stepvise logistic regression indicate a p53
      prognostic value independent from stage and grade (OR 23,4). This result
      indicates that p53 overexpression which can be determined on routine preparation
      has a strong prognostic value and a certain clinical utility.

PMID- 8978143
TI  - [A good model of acute hepatic failure: 95% hepatectomy. Treatment by
      transplantation of hepatocytes].
AB  - The aim of this study was to develop in rats, a model of acute hepatic failure
      that mimics human fulminant hepatitis and to study the effect on survival of
      transplantation of isolated hepatocytes. This study showed that the mortality
      after 90% hepatectomy was reduced by the sole correction of hypoglycemia. On the
      other hand, 95% hepatectomy appeared as a reliable and reproductable model,
      associated with a period of hepatic coma, a deep disorder of coagulation, and a
      high mortality rate (> 80%) despite correction of hypoglycemia. In this model of
      acute hepatic failure, intraperitoneal transplantation of encapsulated isolated
      hepatocytes significantly reduced the mortality rate from 80% in the control
      groups to 31% in the transplanted group. A complete regeneration of the native
      liver was observed in all rats surviving. All animals survived after explantation
      of the hollow fibers. Well preserved hepatocytes were observed in hollow fibers
      two months after transplantation.

PMID- 8978144
TI  - [Expression of mRNA, interleukin-1 beta, interleukin 6 and tumor necrosis factor
      alpha during regeneration of the sciatic nerve in rats after tissue loss].
AB  - Within the family of proinflammatory cytokines, some exhibit a neurotrophic
      activity in addition to their proinflammatory functions. However, their role in
      peripheral nerve regeneration processes is still poorly understood. This study
      presents the kinetics of expression of mRNAs for different cytokines, IL-1 beta,
      IL-6, TNF alpha and that of NGF included as control. It was carried out on the
      rat sciatic nerve regeneration using two models of nerve transection with a 7 mm
      loss of substance. Nerve regeneration took place through an autologous nerve
      grafting in the first model, and through a collagenous cylinder in the second
      one. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was
      used to quantify each mRNA of cytokine and that of actin beta gene considered as
      an endogenous internal standard. The results showed a peak in the expression of
      IL-1 beta mRNAs in both models at D2 (second bay after operation). This D2-peak
      was also observed for TNF alpha and IL-6, but only in the model of the cylinder.
      The level of IL-6 D2-peak was very high compared to the nearly complete absence
      of IL-6 mRNAs expression in non operated control nerves. According to these
      results, proinflammatory cytokines and especially IL-6 may play a major role in
      promoting peripheral nerve regeneration.

PMID- 8978145
TI  - [Streptococcus cellulitis. Apropos of 3 clinical cases].
AB  - We report three cases of streptococci cellulitis of the hand. The characteristic
      clinical presentation suggested streptococcus infection; locoregional edema,
      rash, echymosis, phlyctena and signs of finger ischemia. Operative findings also
      suggested streptococcus infection: swelling of brownish subcutaneous tissue and
      local thrombus formation. There was no true pus formation. Streptococcus was
      identified in all 3 cases. Emergency surgical treatment is needed. The portal is
      opened, followed by extensive fasciotomy and debridement of all necrosed tissue.
      Partial suture is indicated. Antibiotics can be used as an adjunct but are not
      sufficient alone.

PMID- 8978146
TI  - [Trapezoid-metacarpal arthrodesis].
AB  - There is no ideal surgical indication for rhizoarthrosis of the trapezoid
      metacarpal joint. Fusion using two screws or a screw and a pin allow
      solidification after minimal immobilization for 45 days with the thumb placed in
      front of the index. A 1 to 21 year follow-up (mean 68 months) of 30 hands showed
      23 cases of arthrosis and 7 cases of polyarthritis. Overall results were good in
      17 cases, acceptable in 8 and poor in 5. Pain relief was obtained or improved in
      90% of the cases. Radiographically, pseudarthrosis was seen in 10%. No
      reoperations were required. Fusion is an alternative to other surgical approaches
      allowing pain relief and solid grip without the major problems related to
      prostheses.

PMID- 8978147
TI  - [Surgical rehabilitation of the upper limbs in tetraplegic patients].
AB  - Use of the hands is highly limited in most tetraplegia patients considerably
      reducing their self-sufficiency. Over the last fifteen years, surgical
      rehabilitation of the upper limb has been undertaken with satisfactory results.
      We report our personal series of 62 operations in 28 patients over the last 6
      years. Satisfactory results were obtained in all cases. The patients must be
      fully informed about the operation in order to understand what can be expected
      and the need for prolonged care in a rehabilitation center. Close collaboration
      with the rehabilitation physician is essential.

PMID- 8978148
TI  - [Research and therapeutics in osteoarthritis. The route of interleukin-1
      inhibitors].

PMID- 8978149
TI  - [Epidemiology of knee osteoarthritis: results of the longitudinal study of
      Baltimore on the aging].

PMID- 8978150
TI  - [Physiopathology of arthrotic cartilage].

PMID- 8978151
TI  - [Effects of growth factors on the articular cartilage].

PMID- 8978152
TI  - [Radiological evaluation of osteoarthritis].

PMID- 8978153
TI  - [Measurement of joint space pinching in osteoarthritis: methods, value and
      limitations].

PMID- 8978154
TI  - [Exercise and osteoarthritis].

PMID- 8978155
TI  - [Regulation of collagen from the cartilage by interleukin-1].

PMID- 8978156
TI  - [Repair of the articular cartilage after exposure to interleukin-1].

PMID- 8978157
TI  - [Diacetylrhein administrated "curatively" in an experimental model of post
      contusion osteoarthritis in rabbits].

PMID- 8978158
TI  - [Why pragmatic trials of the treatment of osteoarthritis? Application to the
      pragmatic study of diacetylrhein].

PMID- 8978159
TI  - [Epidemiology of acute bronchopulmonary infections in children].
AB  - In infants and young children acute lower respiratory infection is the most
      common cause of morbidity and death especially in developing countries. Factors
      that contribute to the increased susceptibility to respiratory pathogens include
      young age, season, sex, indoor pollution, large family size, malnutrition, low
      immunocompetence, socioeconomic disadvantage. The epidemiology of acute
      respiratory infections in childhood seems similar worldwide. In all countries,
      respiratory syncytial virus, parainfluenzae virus 1 and 3 influenzae A and B
      viruses and adenovirus are reported to be the main causes of acute respiratory
      infections. Six microorganisms are responsible of 90% of documented acute
      bacterial pulmonary infections, Streptococcus pneumoniae, Mycoplasma pneumoniae,
      Chlamydia pneumoniae, Chlamydia trachomatis, Haemophilus influenzae,
      Staphylococcus. Mixed viral and bacterial infections occur frequently (30%). The
      role of respiratory viruses in predisposing to colonization and invasion of
      bacterial organisms has often been suggested. In recent years acquired resistance
      against antibiotic for H. influenzae and S. pneumoniae has emerged.

PMID- 8978160
TI  - [Diagnosis of acute bronchopulmonary infections in children].
AB  - Positive diagnosis of acute bronchopneumopathy in the child is relatively easy,
      but defining its aetiology is another matter. Criteria to distinguish between
      pneumopathy of viral or of bacterial origin should be known but are often on the
      wrong track. Some clinical and radiological pictures, associated with
      epidemiological data, can also orient toward an infectious agent and should be
      taken into account. When clinical severity or the background requires precise
      diagnosis in order to better adapt the treatment, a choice will need to be made
      among the numerous techniques now available to detect the responsible infectious
      agent.

PMID- 8978161
TI  - [Viral bronchiolitis and pneumopathies in infants].
AB  - Acute bronchiolitis is the most common severe lower-respiratory-tract infection
      of infancy. Although signs and symptoms may become severe, most viral respiratory
      infections are self-limited and improvement occurs within a few days. Patients
      hospitalized with bronchiolitis usually require supportive therapy, including
      oxygen and fluids, and may require mechanical ventilation. A trial of aerosolized
      beta 2-agonist is warranted in patients with bronchiolitis. Systemic
      corticosteroids have not been proved efficacious. Inhaled corticosteroids may be
      useful in reducing the severity of chronic wheezing that may follow acute
      bronchiolitis. Ribavirin may be considered in patients with severe disease of
      those at high risk for severe disease.

PMID- 8978162
TI  - [Acute viral respiratory infections and asthma].
AB  - Respiratory viral infections are very important triggers of asthma exacerbation.
      Recent epidemiologic studies support the hypothesis that they are associated with
      80 to 85% of acute attacks of asthma in children. The respiratory syncytial and
      parainfluenza viruses are predominantly detected in infants, while rhinovirus and
      mycoplasma are the commonest in children. In practice for an asthmatic child, it
      is necessary: 1. to vaccinate against influenza; 2. resume or increase the
      inhaled antiinflammatory therapeutics in moderate to severe asthma, before the
      viral epidemic season; 3. teach the child and his family on the attitude to have
      during an upper respiratory infection and when to visit a physician.

PMID- 8978163
TI  - [Bronchopulmonary infections caused by Mycoplasma pneumoniae in children].
AB  - Mycoplasma pneumoniae, a gram-negative bacteria, is an important cause of lower
      respiratory tract infection in children (20% of cases). The infection tends to be
      endemic and is punctuated by epidemic episodes every 4 to 7 years. Its frequency
      seems to be higher in children between 5 and 9 years of age, but is probably
      underestimated before 5 years. M.pneumoniae may cause multisystem infection.
      Diagnosis is established upon clinical data and laboratory findings. Usually, the
      infection is associated with leucocyte count under 15,000/mL and C-reactive
      protein under 50 m/L. Detection of M. pneumoniae DNA in clinical samples appears
      to have advantages over serological tests. Severe infections have been described
      in patients with humoral and cellular immunodeficiencies, sickle cell disease,
      cystic fibrosis. Treatment with macrolids and tetracyclines (after 8 years of
      age) is indicated. Respiratory functional sequelae are possible.

PMID- 8978164
TI  - [Pulmonary Chlamydia infections in children].
AB  - In the last decades chlamydial infection of the respiratory tract have been
      described in children. Chlamydia trachomatis, the most common identifiable cause
      of neonatal infections conjunctivitis is also a recognised cause of pneumonia in
      newborns and is responsible for about one third of sexually transmitted disease.
      Chlamydia psittaci is mainly pathogenic for birds and occasionally for human.
      More recently Chlamydia pneumoniae has been found associated with pulmonary
      abnormalities, nasopharynx and pulmonary oropharynx infections. Microbiologic
      diagnosis can be difficult. Several non culture methods are now available such as
      the direct fluorescent antibody test and enzyme immuno-assays. X ray chest show a
      reticulated and (or) nodular pattern. Treatment is mainly macrolide based with
      erythromycin.

PMID- 8978165
TI  - [Pneumopathies in immunosuppressed children].
AB  - Pneumonia in immunodeficient child is a frequent and dramatic event, with a high
      risk of mortality. Pneumonia requires immediate management. Multiplicity of
      causes makes diagnosis difficult. Broncho-alveolar lavage must be the first
      investigation to carry out while waiting for the results of investigations, rapid
      and efficient treatment is based on probabilistic reasoning which must take the
      type of immunodeficiency into account. Prophylaxis is still the best way to
      improve prognosis of pneumonia in immunodeficient children.

PMID- 8978166
TI  - [Antibiotic strategy in lower respiratory infections in children].
AB  - Antibiotic treatment of community-acquired lower respiratory tract infections in
      children remains widely empiric since the determination of the causative agent is
      difficult and rarely done. Antibiotic therapy is not necessary in all cases since
      viral infections are frequent. Antibiotic choice must take in account the
      possibility of pneumococcal infections. Pneumococci are not the most frequent
      causative agent but always provoke severe infections with a risk of death and
      amoxicillin is the first-line choice, with high doses (100 mg/kg/d) because of
      the emergence of strains with a reduced sensitivity to penicillin. In younger
      children, Haemophilus influenzae infections are frequent and clavulanic acid must
      be associated. When intravenous route is required, 3rd generation cephalosporins
      are useful. The clinical failure of beta-lactams antibiotics is widely due, after
      the age of two years, to a Mycoplasma pneumoniae infection and a macrolide is
      required as second-line choice. Markers specific of viral infection are needed in
      children to reduce antibiotic prescription.

PMID- 8978167
TI  - [Pulmonary pneumocystosis and cerebral toxoplasmosis in patients with HIV
      infection. Diagnosis, development, treatment, prevention].

PMID- 8978168
TI  - [Nontraumatic spinal cord compression. Etiology, physiopathology, diagnosis,
      principles of the treatment].

PMID- 8978169
TI  - [Rheumatoid polyarthritis. Pathological anatomy, diagnosis, development,
      prognosis, treatment].

PMID- 8978170
TI  - [Parkinson disease. Etiology, physiopathology, diagnosis, development,
      treatment].

PMID- 8978171
TI  - [Non-tuberculous acute salpingitis. Etiology, diagnosis, development, prognosis,
      treatment].

PMID- 8978172
TI  - [Causes and evolutive profiles of osteoarthrosis].
AB  - In osteoarthritis, risk factors, clinical expression and outcome are greatly
      heterogeneous. This heterogeneity is observed not only from one subject to
      another but depends also on the site of osteoarthritis. Risk factors are not
      necessarily the same as those marking a worse prognosis. For these factors,
      general risk factors influencing or marking a generalized predisposition to the
      condition and local risk factors resulting on abnormal biomechanical loading at
      specific joint sites must be distinguished.

PMID- 8978173
TI  - [Cartilage degradation and articular inflammation].
AB  - Osteoarthritis is mainly characterized by cartilage degradation as a result of
      series of pathological processus still not well understood. In recent years much
      interest has centered on the contribution of cytokines to cartilage degradation:
      characterization of cytokines extracted from normal and pathological
      articulation, site of production (synoviocytes, chondrocytes, osteoblasts) and
      their role on the production of proteases, protease inhibitors or other types of
      molecules implicated in osteoarthritis. Several types of cytokines such as IL 1
      beta and TNF alpha, known as proinflammatory factors in rheumatoid arthritis,
      have been shown to be present in the synovial fluid from osteoarthritic patients.
      Recent experimental data allow us to better understand the cellular and molecular
      mechanisms of the cytokines respectively involved into rheumatoid arthritis and
      osteo-arthritis.

PMID- 8978174
TI  - [Joint osteoarthritis and rhizarthrosis].
AB  - Articular joint disease frequently occurs in women during menopause. It mainly
      affects the terminal interphalangeal joints (and is responsible for the formation
      of small, hard nodules, known as Heberden's nodes) and the metacarpophalangeal
      joint the thumb (root arthrosis). Clinical diagnosis is not difficult and the
      disorders are often little troubling and considered only secondary in an overall
      functional context. However, they can change the quality of life of these
      patients, making many daily activities difficult to perform. They thus remain a
      common reason for outpatient visits, although their disfiguring nature is
      sometimes the main motivation of these patients.

PMID- 8978175
TI  - [Gonarthroses].
AB  - Osteoarthritis of the knee joint can affect femoro-tibial as femoro-patellar
      compartments. It is a frequent and disabling location of the disease which may
      induce pain at motion and stiffness. Swelling of the knee is very frequent and
      synovial fluid is easy to puncture. Roentgenologically, the AP view, in standing
      position, with a 30 degree flexion is useful to depict mild narrowings of the
      femoro-tibial joint space. Knee is the main joint used for clinical trials in
      osteoarthritis because: 1. it is frequent location of the disease; 2. its
      handicap is relevant; 3. validated assessment criteria are available. As knee
      joint is superficial, femoro-tibial osteoarthritis may benefit by local
      treatments in addition to general usual management.

PMID- 8978176
TI  - [Coxarthroses].
AB  - Osteoarthritis of the hip is a frequent disease affecting 2 to 4% adults. The
      main symptoms are inguinal pain, hip movement limitation and thigh muscular
      atrophy. The diagnosis is usually made of on antero-posterior radiograph of the
      pelvis and Lequesne's lateral view that show joint space narrowing and
      osteophytosis. There is no correlation between radiographic lesions and clinical
      symptoms. The mean rate of joint space narrowing progression was shown to be of
      about 0.30 mm/year but inter-patients variations are very large. The evolution is
      more sever in older patients and when there is no osteophyte. New imaging
      techniques are necessary only if diagnosis is impossible on standard radiographs
      but not for the surgical decision. The treatment of hip osteoarthritis requires
      analgesic, NSAIDs and symptomatic slow actin drugs for osteoarthritis. Total hip
      arthroplasty is necessary when medical treatment is non effective on pain and
      disability.

PMID- 8978177
TI  - [Cervical spine osteoarthritis].
AB  - Cervical spine is particularly susceptible to anatomical osteoarthritis, but in a
      good half cases it remains asymptomatic. Painful cervical spine osteoarthritis
      results in neck pain, sometimes acute, more commonly chronic. But cervical
      osteoarthritis may induce compression of the neurovascular structures contained
      into the cervical spine: upper arm nerve root pain by nerve root compression;
      myelopathy by spinal cord compression; sometimes vertebro-basilar insufficiency
      by compression of vertebral arteries.

PMID- 8978178
TI  - [Lumbar osteoarthritis].
AB  - Lumbar osteoarthritis involves both the disc and the facet joints. Measurements
      of the disc space evaluates the degeneration. There is no radio-clinical
      correlation at a given time. There are however inflammatory phases in facets
      arthrosis and discolysis with disc narrowing within few months. These attacks are
      responsive to NSAID'S and local injections of corticosteroids. The chronic back
      pain needs only analgesics and rehabilitation. Osteophytes can narrow the spinal
      canal and induce back and leg pains. Except neurological weakness and bladder
      dysfunction the medical treatment should be prolonged before the indication of
      surgery.

PMID- 8978179
TI  - [General therapeutic principles of osteoarthritis].
AB  - New approaches in the treatment of osteoarthritis are possible and necessary,
      based on new advances. It is a disease which can be in part prevented and
      treated. We are often able to insure a primary prevention, to give treatments
      which can reduce pain and disability, the main clinical features. To reduce the
      risk factors, to organize a psychosocial support (by phone contacts against
      loneliness), to inform patients and to use all the nonpharmacologic physical
      therapies must be at the foreground. A real prevention of this major health care
      problem and the researches to identify new treatments active on both symptoms and
      anatomical lesions concern searchers and clinicians as well as politic and public
      health authorities.

PMID- 8978180
TI  - [Chronic myeloid leukemia. Diagnosis, course, prognosis].

PMID- 8978181
TI  - [Slow adrenal insufficiency in adults. Etiology, physiopathology, diagnosis,
      treatment].

PMID- 8978182
TI  - [Acute metabolic complications of diabetes (ketoacidosis hypoglycemia,
      hyperosmolarity, lactic acidosis): etiology, physiopathology, diagnosis.
      Emergency treatment of ketoacidosis with posology].

PMID- 8978183
TI  - [Pulmonary embolism. Etiology, physiopathology, diagnosis, course, treatment].

PMID- 8978184
TI  - [Anorexia nervosa and bulimia in adolescents. Diagnosis, treatment].

PMID- 8978185
TI  - [Classification and epidemiology of thyroid tumors].
AB  - Thyroid diseases are the most prevalent endocrine diseases. Faced with a thyroid
      enlargement or nodule, it is a challenge for the physician to determine with the
      best sensibility and specificity and the least cost which one are benign tumours
      and which are malignant neoplasms that need to be removed. The prevalence of
      solitary nodules is 1 to 5%. Only 2 to 12% of these nodules are cancers.
      Papillary and follicular carcinomas, two carcinomas derived from follicular
      cells, are the most common types and occur more frequently in women. Both have a
      good prognosis. Medullary carcinoma derives from C-cells. Familial forms have to
      be searched. Anaplastic carcinoma and other malignant tumours are less frequent
      but have poor prognosis.

PMID- 8978186
TI  - [Differentiated thyroid epithelioma].
AB  - Long term prognosis of differentiated thyroid carcinoma is favourable, being
      modulated by several factors, age and histology being the most relevant. Initial
      treatment includes firstly surgery: loboisthmusectomy in case of intra-thyroid
      tumor, unifocal, less than 1.5 cm in diameter in patients with favourable
      prognostic indicators, total thyroidectomy with the administration of an ablative
      dose of 131l in all the other patients. A routine dissection of the paratracheal
      groove and of the supraclavicular area is performed in all patients. L-thyroxine
      treatment is given to all patients. Relapses should be discovered early; this is
      made possible by the combined use of serum thyroglobulin measurements and of 131l
      total body scans.

PMID- 8978187
TI  - [Medullary cancer of the thyroid].
AB  - Although rare (10% of thyroid cancers), medullary thyroid cancer is remarkable by
      the presence of a specific biological marker; elevation of blood calcitonin. It
      allows its preoperative diagnosis and this extensive surgery which is the only
      efficient treatment. The possibility of hereditary form (30%) must always be kept
      in mind; they can now be detected by genetic screening since specific mutations
      on Ret gene have been recently discovered. Follow up and early treatment of at
      risk subjects in a family is therefore possible and permits definitive surgical
      cure.

PMID- 8978188
TI  - [Management of a thyroid nodule].
AB  - Whenever a thyroid nodule is detected, the crucial question is whether it is
      benign or malignant. Apart from surgery, the most accurate assessment is provided
      by cytologic result. Provided the limitations and constraints of the procedure
      are understood, especially the need to repeat fine needle aspiration biopsy with
      time and to have the specimens read by highly experienced cytologists a
      significant number of surgical operations can be avoided according to
      circumstances. Except in some special cases, scintigraphy may be discarded
      because echography is more accessible, lest costly and more discriminating with
      regard to the surrounding parenchyma. Also, it is not necessary to prescribe
      hormonal therapy either before or after surgery, if the gland remains under
      euthyroid conditions; the epidemiological data available are not conclusive
      enough to justify such a prescription.

PMID- 8978189
TI  - [Cytopuncture in tumors of the thyroid].
AB  - In a large review on the utility of fine needle aspiration biopsy of the thyroid
      in the diagnostic management of nodular thyroid disease, procedure, morphological
      diagnostic criteria and difficulties, complementary technics are overviewed.
      Relevant articles and series are reviewed to assess the results of fine needle
      aspiration biopsy. A question is highlighted: wether benign unoperated thyroid
      nodules diagnosed by fine needle aspiration biopsy are they an underestimate risk
      group.

PMID- 8978190
TI  - [Thyroid microcancer].
AB  - The prevalence of papilliary thyroid microcarcinomas is very high. A great
      majority has an excellent prognosis. However some of them lead to local
      recurrences or distant metastasis. Therefore it should be important do detect
      high risk factors to choose between conservative or aggressive treatment. However
      this proves to be difficult and it seems reasonable to perform in most instances
      a total or near total thyroidectomy with nodal disection. TSH suppression
      treatment is routinely advocated but not adjunctive radioiodine ablation. This
      approach authorizes an easier long term follow up.

PMID- 8978191
TI  - [Risks and complications of thyroid surgery].
AB  - Despite technical improvements, complications may still occur after thyroid
      surgery, mostly after total thyroidectomy, removal of diving or suffocating
      goiters for Graves' disease or carcinoma, and in reoperations. Hypoparathyreosis
      or unilateral recurrent laryngeal nerve palsy are observed in 10% of the patients
      but persist in only 1% of the cases managed by orthophony or vitaminocalcic
      supply. Two early complications are severe respiratory obstruction by bilateral
      nerve palsy and suffocating haematoma. Claude-Bernard Horner syndrome,
      lymphorrhea, abscess or disgraciods scar are rarely observed. The prevention of
      these complications requires adequate surgical indications performed by
      specialized endocrine surgeons.

PMID- 8978192
TI  - [Antibiotics. General data on modes of action and mechanisms of resistance].

PMID- 8978193
TI  - [Electrocardiographic symptomatology of auricular fibrillation and flutter].

PMID- 8978194
TI  - [Auricular fibrillation. Diagnosis, complications, treatment].

PMID- 8978195
TI  - [Autism in children. Diagnosis, course, treatment].

PMID- 8978196
TI  - [Chronic lymphoid leukemia. Diagnosis, course, prognosis, treatment].

PMID- 8978197
TI  - [Multiple sclerosis. Epidemiology, diagnosis, course, prognosis].

PMID- 8978198
TI  - [Is spinal arthrosis painful?].

PMID- 8978199
TI  - [Doppler ultrasonography of the skull: methodology and clinical applications].

PMID- 8978200
TI  - [Epidemiology of sexually transmitted diseases, with the exception of AIDS].
AB  - Epidemiologic trends in sexually transmitted diseases strongly vary in the world.
      The situation is worrying in the developing countries. Both the incidences and
      prevalences are very high antibiotic resistance is expanding and interactions
      between sexually transmitted diseases and human immunodeficiency virus contribute
      to AIDS epidemic. In western Europe, the decline of some sexually transmitted
      diseases is likely to be linked with successful control programmes and gonorrhea
      and syphilis now are rare diseases. The USA situation is contrasted. Some inner
      city minority population still have high level of gonorrhea and are concerned
      with resurgence of syphilis and chancroid. Chlamydia trachomatis infections,
      which are a major, cause of infertility and ectopic pregnancy, have become the
      most prevalent sexually transmitted disease in industrialized world.

PMID- 8978201
TI  - [Early syphilis].
AB  - Given the transmission of Treponema pallidum during human sexual contact,
      syphilis now occurs in France only in sexually high-risk, disadvantaged
      populations. The English-language terminology of "early syphilis" has
      progressively replaced that of "primary" and "secondary" in French usage.
      Induration of the chancre and the papular nature of secondary skin rashes remain
      the best criteria for clinical diagnosis. Serological tests associate test
      specific for treponematoses (Treponema pallidum haemagglutination assay, TPHA)
      and a nonspecific screening test (Venereal diseases research laboratory, VDRL) to
      confirm clinically suspected disease. Routine use of long-acting penicillin
      (benzathine penicillin) is consistently effective. The continuing risk of active
      syphilis in a pregnant woman and the possibility of severe syphilis in HIV
      patients require vigilance.

PMID- 8978202
TI  - [Genital papillomavirus infections].
AB  - The incidence of condyloma acuminata is increasing in all developed countries
      with highest rates recorded for young sexually males and females, between the
      ages of 16 and 25 years. Subclinical and latent genital human papillomavirus
      (HPV) infections are highly prevalent. Direct correlation between number of
      sexual partners and presence of HPV is evident. Clinical HPV infections such as
      condylomas (acuminata and papular) are easily recognized, but acetowhite flat
      macular condylomas require colposcopic examination. High grade IN (cervical CIN
      II, III, vulvar VIN, anal AIN, penile PIN) are considered to be related to HPV
      type 16 and 18 (less frequently other types 31, 33, 35, 51), the oncogenic
      potential of which was demonstrated by in vitro transformation assays and by the
      fact that they are detected in 50 to 90% of genital neoplasia. Clinical HPV
      infections (condylomas and low grade IN) are associated with "low risk" HPV types
      6/11. The requirement for routine HPV-DNA typing is limited and in general,
      management is based on clinical and conventional light microscope evaluation.
      Immunosuppression is a most important risk-factor for the development, the
      progression and the recurrences of cervical and anal condylomas and neoplasia.
      Whatever treatment is applied a 30% recurrences rates occur, implying a regular
      clinical follow up after treatment to prevent recurrences development and
      neoplasia.

PMID- 8978203
TI  - [Vulvovaginitis].

PMID- 8978204
TI  - [Management of male urethritis].

PMID- 8978205
TI  - [Sexually transmitted diseases in children].
AB  - Sexually transmitted diseases in children include vertically transmitted diseases
      responsible for severe fetopathy and neonatal diseases as well as infections
      acquired in the postnatal period. Sexually transmitted diseases in children raise
      the question of possible of sexual abuse, which has major medicolegal, social and
      psychological implications. The proof of sexual abuse is further complicated by
      the fact that some neonatal infections can be revealed only at a later stage.
      Moreover in rare cases venereal diseases are transmitted by non sexual contact.
      Early sexual activity, should also be included (10% of children have their first
      sexual intercourse before the age of 15).

PMID- 8978206
TI  - [Psychological aspects of sexually transmitted diseases].
AB  - The psychological aspects of sexually transmitted diseases first refer to the
      psychological consequences on the patient himself and also on his affective
      circle. The intensity of these consequences shows the importance, in every
      subject, of the fantasies about sexually transmitted diseases which have always
      threatened sexuality. Therefore these fantasies also affect the cares. The
      latter's fantasies can sometimes weaken the precarious psychological balance of
      the patient himself and of his affective circle. This can be confirmed in the
      case of a sexually transmitted disease in one of the partners of a couples or in
      the case of a sexually transmitted disease after sexual abuse. Sometimes,
      psychological factors play an important role in the onset of a sexually
      transmitted disease in a subject. For example, adolescence which promotes acting
      out and taking risks exposes young people to sexually transmitted diseases. In
      the other respects, it has been demonstrated that recurrences of the genital
      herpes simplex virus could be linked to psychosocial factors. In any case, it is
      the doctor-patient dialogue which is the best guarantor of an effective the
      repeutic and preventive action.

PMID- 8978207
TI  - [Acute dehydration in infants. Physiopathology, diagnosis, development,
      treatment].

PMID- 8978208
TI  - [Electrocardiographic study of atrio-ventricular block, bundle branch blocks,
      extrasystole and ventricular tachycardia].

PMID- 8978209
TI  - [Varicella and herpes zoster. Epidemiology, physiopathology, diagnosis,
      development, treatment].

PMID- 8978210
TI  - [Alcoholism: acute and chronic intoxication. Diagnosis, treatment].

PMID- 8978211
TI  - [Alcoholism: withdrawal syndrome. Diagnosis, treatment].

PMID- 8978212
TI  - [Kidney cancer in adults. Pathology, diagnosis, development, principles of
      treatment].

PMID- 8978213
TI  - Risks associated with consumption of herbal teas.
AB  - Plants have been used for medicinal purposes for centuries. Health-oriented
      individuals are turning to herbal teas as alternatives to caffeinated beverages
      such as coffee, tea, and cocoa and for low-caloric supplements. The popularity of
      herbal tea consumption has increased significantly during the past two decades in
      the U.S. Hundreds of different teas made up of varied mixtures of roots, leaves,
      seeds, barks, or other parts of shrubs, vines, or trees are sold in health food
      stores. Although chemists have been characterizing toxic plant constituents for
      over 100 years, toxicological studies of herbal teas have been limited and,
      therefore, the safety of many of these products is unknown. Plants synthesize
      secondary metabolites that are not essential in the production of energy and
      whose role may be in the defense mechanisms as plant toxins to their interactions
      with other plants, herbivores, and parasites. Pyrrolizidine alkaloids (PAs) were
      among the first naturally occurring carcinogens identified in plant products, and
      their presence in herbal teas is a matter of public health significance. Some
      herbal tea mixtures and single-ingredient herbal teas have been analyzed for
      toxic/mutagenic potential by bioassay and chromatographic techniques. Numerous
      human and animal intoxications have been associated with naturally occurring
      components, including pyrrolizidine alkaloids, tannins, and safrole. Thus, the
      prevention of human exposure to carcinogens or mutagens present in herbal tea
      mixture extracts is crucial. Preparation of infusion drinks prepared from plants
      appears to concentrate biologically active compounds and is a major source of PA
      poisoning. The quantity and consumption over a long period of time is of major
      concern. It is recommended that widespread consumption of herbal infusions should
      be minimized until data on the levels and varieties of carcinogens, mutagens, and
      toxicants are made available.

PMID- 8978214
TI  - Human disease associated with Clostridium perfringens enterotoxin.
AB  - Clostridium perfringens continues to be a common cause of food-borne disease.
      Characteristics of this organism that contribute to its ability to cause food
      borne illness include the formation of heat-resistant spores that survive normal
      cooking/heating temperatures, a rapid growth rate in warm food, and the
      production of enterotoxin (CPE) in the human gut. Time and temperature abuse
      associated with food preparation contributes to the majority of outbreaks of C.
      perfringens food-borne disease. CPE-induced diarrhea has been reported in the
      absence of a defined food vehicle. These cases have been typically associated
      with the elderly and following a course of antibiotic therapy. The incidence of
      CPE-induced diarrhea may be expected to increase with the growing population of
      immunocompromised (disease-, treatment-, or age-induced) individuals. Clostridium
      perfringens has been implicated as a possible contributor to the development of
      SIDS in susceptible individuals. Specifically, it has been hypothesized that CPE
      acts as a triggering agent, initiating the events associated with the development
      of SIDS. Continued refinement of both immunoassays and molecular methods for
      toxin and gene detection, respectively, will facilitate their eventual
      availability as commercial kits, providing rapid and simplified methods for the
      detection of C. perfringens isolates that produce or have the capacity to produce
      CPE as well as other toxins associated with this organism.

PMID- 8978215
TI  - Sentencing mentally disordered offenders.

PMID- 8978216
TI  - Rehabilitation after heart attack.

PMID- 8978217
TI  - Rationing health care.

PMID- 8978218
TI  - Radiotherapy for malignant glioma.

PMID- 8978219
TI  - Talk that works: the rise of cognitive behaviour therapy.

PMID- 8978220
TI  - Aging: a global theme issue.

PMID- 8978223
TI  - Skin lesion removal rationed in Florida.

PMID- 8978224
TI  - Malignant cerebral glioma--I: Survival, disability, and morbidity after
      radiotherapy.
AB  - OBJECTIVE: To describe survival, disability, and morbidity after radiotherapy for
      malignant glioma. DESIGN: Two year prospective study with home interviews with
      patients and relatives. SETTING: Seven neurosurgical and radiotherapy centres in
      London. SUBJECTS: 105 patients aged 21 to 75: 59 had biopsy; 46 had partial
      macroscopic resection; 92 received radiotherapy; and 13 received steroids alone.
      MAIN OUTCOME MEASURES: Survival, time free from disability, and changes in
      disability after treatment. RESULTS: Six and 12 month survival for radiotherapy
      patients was 70% and 39%, respectively. Age, World Health Organisation clinical
      performance status, extent of surgery, and history of seizures before diagnosis
      each influenced survival. The Medical Research Council prognostic index was also
      significantly related to survival. Multivariate analysis showed that initial
      clinical performance status was the most important component of the index. Most
      (80%; 49/61) patients with a clinical performance status of 0, 1, or 2 lived at
      least six months before becoming permanently disabled. Most patients who had
      initially had a good clinical performance status (0-2) and who were alive six
      months after radiotherapy (68%; 36/52), however, had experienced either clinical
      deterioration or severe tiredness after treatment. In 17% (9/52) of these some
      permanent loss of function remained. These adverse effects were associated with
      increasing radiotherapy dose. Severely disabled patients (clinical performance
      status 3 or 4) gained little benefit. CONCLUSION: Severely disabled patients gain
      little physical benefit from radiotherapy, whereas those not so disabled may
      experience considerable adverse effects.

PMID- 8978225
TI  - Malignant cerebral glioma--II: Perspectives of patients and relatives on the
      value of radiotherapy.
AB  - OBJECTIVE: To explore the experiences of patients and relatives after the
      diagnosis and treatment of malignant cerebral glioma. DESIGN: Two year
      prospective study with home interviews. SETTING: Six neurosurgery and
      radiotherapy centres in London. SUBJECTS: 75 patients and 66 close relatives
      interviewed at diagnosis, 58 patients interviewed after radiotherapy, and 27
      interviewed after recurrence. MAIN OUTCOME MEASURES: Awareness of likely
      prognosis, distress, dissatisfaction with radiotherapy, and perception of severe
      problems in everyday life. RESULTS: As they began radiotherapy most patients
      understood that they suffered from a brain tumour (95%; 71/75), but only one
      quarter (19/75) seemed fully aware of the poor prognosis. Others were unaware
      (43%; 32/75) or only partly aware (32%; 24/75). The more aware patients were more
      distressed. Relatives were three times more likely to be aware of the prognosis
      (67%; 44/66) and were more distressed. Although 39% (29/75) of patients initially
      made negative comments about radiotherapy, only 17% (13/75) were completely
      dissatisfied. The decision to accept radiotherapy could be discussed directly
      with 19 fully aware patients. Twelve found radiotherapy acceptable if it were
      medically advised or if it improved survival. Assessed by their own reports of
      problems only 40% of patients achieved a period of stability or remission, yet
      dissatisfaction with treatment did not increase. CONCLUSIONS: Most patients with
      malignant glioma initially seemed unaware or only partly aware of the poor
      prognosis. Relatives were more aware, more distressed, and often concerned to
      protect patients from full awareness, which made it difficult to explore with
      patients directly the possible trade off between quality and length of life.
      Conceptualising the question as a rational choice ignores the social and
      emotional context of life threatening disease.

PMID- 8978226
TI  - Psychological rehabilitation after myocardial infarction: multicentre randomised
      controlled trial.
AB  - OBJECTIVE: To evaluate rehabilitation after myocardial infarction. DESIGN:
      Randomised controlled trial of rehabilitation in unselected myocardial infarction
      patients in six centres, baseline data being collected on admission and by
      structured interview (of patients and spouses) shortly after discharge and
      outcome being assessed by structured interview at six months and clinical
      examination at 12 months. SETTING: Six district general hospitals. SUBJECTS: All
      2328 eligible patients admitted over two years with confirmed myocardial
      infarction and discharged home within 28 days. INTERVENTIONS: Rehabilitation
      programmes comprising psychological therapy, counselling, relaxation training,
      and stress management training over seven weekly group outpatient sessions for
      patients and spouses. MAIN OUTCOME MEASURES: Anxiety, depression, quality of
      life, morbidity, use of medication, and mortality. RESULTS: At six months there
      were no significant differences between rehabilitation patients and controls in
      reported anxiety (prevalence 33%) or depression (19%). Rehabilitation patients
      reported a lower frequency of angina (median three versus four episodes a week),
      medication, and physical activity. At 12 months there were no differences in
      clinical complications, clinical sequelae, or mortality. CONCLUSIONS:
      Rehabilitation programmes based on psychological therapy, counselling, relaxation
      training, and stress management seem to offer little objective benefit to
      patients who have experienced myocardial infarction compared with previous
      reports of smaller trials.

PMID- 8978227
TI  - Prevalence of mental disorder in remand prisoners: consecutive case study.
AB  - OBJECTIVE: To define the prevalence of mental disorder and need for psychiatric
      treatment in new remand prisoners and to determine to what extent these are
      recognised and addressed in prison. DESIGN: Study of consecutive male remand
      prisoners at reception using a semistructured psychiatric interview. SETTING:
      Large remand prison for men (HMP Durham). SUBJECTS: 669 men aged 21 years and
      over on remand, awaiting trial. MAIN OUTCOME MEASURES: Prevalence of mental
      disorder at reception, prisoners need for psychiatric treatment, identification
      of mental disorder by prison reception screening, and numbers placed
      appropriately in the prison hospital. RESULTS: 148 (26%) men had one or more
      current mental disorders (excluding substance misuse) including 24 who were
      acutely psychotic. The prison reception screening identified 34 of the men with
      mental disorder and six of those with acute psychosis. 168 men required
      psychiatric treatment, 50 of whom required urgent intervention; 16 required
      immediate transfer to psychiatric hospital. Of these 50, 17 were placed on the
      hospital wing because of mental disorder recognised at prison screening.
      CONCLUSION: Not only is the prevalence of mental disorder, in particular severe
      mental illness, high in this population, but the numbers identified at reception
      are low and subsequent management in prison is poor.

PMID- 8978228
TI  - Point prevalence of mental disorder in unconvicted male prisoners in England and
      Wales.
AB  - OBJECTIVES: To determine prevalence of mental disorder among male unconvicted
      prisoners and to assess the treatment needs of this population. DESIGN: Semi
      structured interview and case note review of randomly selected cross section of
      male remand population. Non-attenders were replaced by the next name on prison
      roll. SETTING: Three young offenders' institutions and 13 adult men's prisons.
      SUBJECTS: 750 prisoners, representing 9.4% cross sectional sample of male
      unconvicted population. MAIN OUTCOME MEASURES: Prevalence of ICD-10 diagnoses of
      mental disorder, and associated treatment needs. RESULTS: Psychiatric disorder
      was diagnosed in 469 (63%) inmates. The main diagnoses were: substance misuse,
      285 (38%); neurotic illness, 192 (26%); personality disorder, 84 (11%);
      psychosis, 36 (5%); other and uncertain, 36 (0.5%). Subjects could have more than
      one diagnosis. The average refusal rate was 18%. In total 414 inmates (55%) were
      judged to have an immediate treatment need: transfer to an NHS bed, 64 (9%);
      treatment by prison health care services, 131 (17%); motivational interviewing
      for substance misuse, 115 (15%); and therapeutic community placement, 104 (14%).
      CONCLUSIONS: Mental disorder was common among male unconvicted prisoners.
      Psychosis was present at four or five times the level found in the general
      population. Extrapolation of our results suggests that remand population as a
      whole probably contains about 680 men who need transfer to hospital for
      psychiatric treatment, including about 380 prisoners with serious mental illness.

PMID- 8978229
TI  - Video assessment of simple respiratory signs.

PMID- 8978230
TI  - An endoluminal brush to detect the infected central venous catheter in situ: a
      pilot study.

PMID- 8978231
TI  - Prevalence of psychiatric disorders in young people in the care system.

PMID- 8978232
TI  - Fundholders' prescribing costs: the first five years.
AB  - OBJECTIVES: To determine whether the first five waves of English fundholding
      practices have reduced their prescribing costs relative to non-fundholding
      practices, and the duration of any reduction achieved. DESIGN: Analysis of item
      and cost data for all general practices in England in the six years from April
      1990 to March 1996. The practices of each of the first five waves were identified
      at the Prescription Pricing Authority. SETTING: All general practices in England.
      MAIN OUTCOME MEASURES: Changes and rates of change in net ingredient cost per
      prescribing unit, and changes in number of items per prescribing unit in
      fundholding practices, before and after fundholding, relative to continuing non
      fundholders. RESULTS: Absolute prescribing costs increased over the six years, by
      66% in the continuing non-fundholders and by 56-59% for fundholders. Successive
      waves of fundholders showed a similar pattern of change: a small relative
      reduction in the pre-fundholding year, maximum relative reduction in the first
      year, and a declining relative reduction in the second and third years. After
      this, their increases in costs were largely similar to those of non-fundholders.
      The number of items dispensed remained stable over the six years in all groups.
      CONCLUSIONS: The real budgets operated by fundholders were associated with a
      reduction in costs of about 6% relative to continuing non-fundholders, and this
      saving seemed to be retained during the study. The relative reduction was small
      compared with the absolute increase seen in all groups and disappeared after the
      third year of fundholding. It was brought about by lowering the average cost per
      item rather than by giving fewer items.

PMID- 8978233
TI  - Atrial fibrillation in elderly patients: prevalence and comorbidity in general
      practice.

PMID- 8978234
TI  - Ambulatory blood pressure monitoring: a guide for general practitioners.

PMID- 8978235
TI  - Intravenous antimicrobial therapy in the community: underused, inadequately
      resourced, or irrelevant to health care in Britain?
AB  - The NHS Executive is keen to promote "hospital at home" services in Britain, as
      part of its philosophy of keeping more care in the community and also to relieve
      the increasing demand for hospital beds. One such service is the provision of
      intravenous antimicrobial therapy in the community. Yet, compared with the United
      States, where home or outpatient intravenous antimicrobial therapy programmes are
      well developed, experience in Britain and Europe is limited, reflecting a
      difference in cultural attitudes and healthcare structures between the two
      continents. Only a few units in Britain currently run home intravenous
      antimicrobial therapy programmes, and several issues need to be addressed if more
      treatment is to be provided outside hospital. These include an assessment of the
      need for community intravenous antibiotic treatment and which patient groups many
      benefit. The main motive for community intravenous treatment should be better
      patient care and not simply a reduction in healthcare costs. At present the pace
      of change is being set by a few clinical enthusiasts and by commercial
      organisations, whereas the NHS deserves a more organised strategy for purchasing
      treatment with intravenous antibiotics in the community.

PMID- 8978236
TI  - Grand rounds--Hammersmith Hospital. Persistent fever in pulmonary tuberculosis.

PMID- 8978237
TI  - Routine follow up of breast cancer in primary care. Follow up by non-specialists
      should not be encouraged.

PMID- 8978238
TI  - Routine follow up of breast cancer in primary care. Study of open access centre
      for patients with breast cancer is planned.

PMID- 8978239
TI  - Routine follow up of breast cancer in primary care. More use should be made of
      specialist nurses.

PMID- 8978240
TI  - Routine follow up of breast cancer in primary care. Open door and listening ear
      are best support for patients.

PMID- 8978241
TI  - Routine follow up of breast cancer in primary care. Most recurrences after breast
      conservation are detected by regular hospital visits.

PMID- 8978242
TI  - Audit commission's report was based on large samples and up to date data.

PMID- 8978243
TI  - Child protection. Referrals to social services may be damaging.

PMID- 8978244
TI  - Child protection. Child's needs should be central.

PMID- 8978245
TI  - Child protection. Girl should have been offered a chance of safety.

PMID- 8978246
TI  - Prodigy, a computer assisted prescribing scheme. Interim data show that it is
      worth taking the scheme further.

PMID- 8978247
TI  - Prodigy a computer assisted prescribing scheme. Decisions will be taken after
      receipt of final report next autumn.

PMID- 8978248
TI  - Spinal cord injuries have fallen in rugby union players in New South Wales.

PMID- 8978249
TI  - Relation between treatment benefit and underlying risk in meta-analysis. Standard
      of "label invariance" should not be abandoned.

PMID- 8978250
TI  - Britain was healthier than Germany in 1914.

PMID- 8978251
TI  - Influences of practice characteristics on prescribing in practices. Multiple
      regression models depend on explanatory variables included.

PMID- 8978252
TI  - Postal surveys in general practice. More analytical studies should be carried
      out.

PMID- 8978254
TI  - Scotland's new chief medical officer welcomes reforms of training.

PMID- 8978255
TI  - Adverse events associated with mefloquine. Study in returned travellers confirms
      authors' findings.

PMID- 8978256
TI  - Adverse events associated with mefloquine. Women may be more susceptible to
      adverse events.

PMID- 8978257
TI  - Adverse events associated with mefloquine. Manufacturer should also give
      incidence of "severe" adverse events.

PMID- 8978258
TI  - Adverse events associated with mefloquine. Risk-benefit ratio must be taken into
      account.

PMID- 8978259
TI  - Adverse events associated with mefloquine. Explaining about possible adverse
      events may reduce problems.

PMID- 8978260
TI  - Adverse events associated with mefloquine. Advice to warn patients about rare
      side effects overturns accepted practice.

PMID- 8978261
TI  - Adverse events associated with mefloquine. Patients may start to take cheaper
      over the counter regimens.

PMID- 8978262
TI  - Effect of deletion polymorphism of angiotensin converting enzyme gene on
      progression of diabetic nephropathy.

PMID- 8978263
TI  - Course on basic surgical skills is being run by all surgical colleges.

PMID- 8978264
TI  - Conflict of interest. Conflict of interest statement should be abolished.

PMID- 8978265
TI  - Conflict of interest. Does the BMJ attempt independent ascertainment?

PMID- 8978266
TI  - Summative assessment in general practice. Scheme is essential to protect public
      and train doctors to required standard.

PMID- 8978267
TI  - Summative assessment in general practice. Scheme has to be compulsory for proper
      evaluation.

PMID- 8978268
TI  - Summative assessment in general practice. Procedure is too complex and intrusive.

PMID- 8978269
TI  - Summative assessment in general practice. More registrars are being trained in
      consultation skills now.

PMID- 8978270
TI  - Summative assessment in general practice. Content validity of video recorded
      consultations needs to be proved.

PMID- 8978271
TI  - Childbirth practice should take women's wishes into account.

PMID- 8978272
TI  - Tissue-specific regulation of iron metabolism and heme synthesis: distinct
      control mechanisms in erythroid cells.

PMID- 8978273
TI  - Telomerase activity in reactive and neoplastic lymphoid tissues: infrequent
      detection of activity in Hodgkin's disease.
AB  - We used the recently described sensitive and rapid detection assay called
      telomeric repeat amplification protocol (TRAP) to detect telomerase activity in
      lymphoblastoid (n = 5) and lymphoma cell lines (n = 7), hyperplastic lymph nodes
      (n = 6) and tonsils (n = 5), and tissues involved by non-Hodgkin's lymphoma (NHL)
      (n = 43) and Hodgkin's disease (HD) (n = 14). Clearly evident telomerase activity
      was found in all lymphoblastoid and lymphoma cell lines, and in 34 of 43 cases
      (80%) of NHL. These results were expected because of the proliferative and
      immortal nature of the cell lines and most malignant cells. However, positive
      results were obtained with the TRAP assay in all hyperplastic lymph nodes and
      tonsils, which raises the issue of derepression of telomerase activity during an
      immune response. Telomerase activity alone therefore does not distinguish
      malignant lymphoid proliferations from reactive states. Telomerase activity was
      detected in only 1 of 14 cases (7%) of lymphoid tissues involved by HD. Eight of
      the 13 negative cases were considered to be interpretable because of the lack (3
      of 13 cases) or low level (5 of 13 cases) of telomerase inhibition. The five
      remaining cases could not be evaluated because of their telomerase inhibitor
      content. The findings imply either transient or very low levels of telomerase
      activity in HD or that HD for the greater part is a telomerase-independent
      neoplasm. Microdissection studies are needed to identify subsets of cells
      carrying telomerase activity in both reactive and neoplastic lymphoid tissues.

PMID- 8978274
TI  - Association of erythrodermic cutaneous T-cell lymphoma, superantigen-positive
      Staphylococcus aureus, and oligoclonal T-cell receptor V beta gene expansion.
AB  - Forty-two patients with cutaneous T-cell lymphoma, including 31 with exfoliative
      erythroderma or Sezary syndrome and 11 with mycosis fungoides, were studied for
      the occurrence of staphylococcal infection. Thirty-two of 42 (76%) had a positive
      staphylococcal culture from skin or blood. One half of the patients with positive
      cultures grew Staphylococcus aureus. This group included 11 with Sezary syndrome
      and 5 with rapidly enlarging mycosis fungoides plaques or tumors. All of the S
      aureus carried enterotoxin genes. Surprisingly, 6 of 16 strains were the same
      toxic shock toxin-1 (TSST-1)-positive clone, designated electrophoretic type (ET)
      41. Analysis of the T-cell receptor V beta repertoire in 14 CTCL patients found
      that only 4 had the expected monoclonal expansion of a specific V beta gene,
      whereas 10 had oligoclonal or polyclonal expansion of several V beta families.
      All patients with TSST-1+ S aureus had overexpansion of V beta Z in blood and/or
      skin lesions. These studies show that S aureus containing superantigen
      enterotoxins are commonly found in patients with CTCL especially individuals with
      erythroderma where they could exacerbate and/or perpetuate stimulate chronic T
      cell expansion and cutaneous inflammation. Attention to toxigenic S aureus in
      CTCL patients would be expected to improve the quality of care and outcome of
      this patient population.

PMID- 8978275
TI  - Retroviral-mediated gene transfer of gp91phox into bone marrow cells rescues
      defect in host defense against Aspergillus fumigatus in murine X-linked chronic
      granulomatous disease.
AB  - The X-linked form of chronic granulomatous disease (X-CGD), an inherited
      deficiency of the respiratory burst oxidase, results from mutations in the X
      linked gene for gp91phox, the larger subunit of the oxidase cytochrome b. The
      goal of this study was to evaluate the impact of retroviral-mediated gene
      transfer of gp91phox on host defense against Aspergillus fumigatus in a murine
      model of X-CGD. Retrovirus vectors constructed using the murine stem cell virus
      (MSCV) backbone were used for gene transfer of the gp91phox cDNA into murine X
      CGD bone marrow cells. Transduced cells were transplanted into lethally
      irradiated syngeneic X-CGD mice. After hematologic recovery, superoxide
      production, as monitored by the nitroblue tetrazolium (NBT) test, was detected in
      up to approximately 80% of peripheral blood neutrophils for at least 28 to 35
      weeks after transplantation. Neutrophil expression of recombinant gp91phox and
      superoxide production were significantly less than wild-type neutrophils.
      However, 9 of 9 mice with approximately 50% to 80% NBT+ neutrophils after gene
      transfer did not develop lung disease after respiratory challenge with 150 to 500
      A fumigatus spores, doses that produced disease in 16 of 16 control X-CGD mice.
      In X-CGD mice transplanted with mixtures of wild-type and X-CGD bone marrow, > or
      = 5% wild-type neutrophils were required for protection against A fumigatus
      challenge. These data suggest that expression of even low levels of recombinant
      gp91phox can substantially improve phagocyte function in X-CGD, although
      correction of very small percentage of phagocytes may not be sufficient for
      protection against A fumigatus.

PMID- 8978276
TI  - Major histocompatibility complex restriction between hematopoietic stem cells and
      stromal cells in vivo.
AB  - Graft failure is a mortal complication in allogeneic bone marrow transplantation
      (BMT); T cells and natural killer cells are responsible for graft rejection.
      However, we have recently demonstrated that the recruitment of donor-derived
      stromal cells prevents graft failure in allogeneic BMT. This finding prompted us
      to examine whether a major histocompatibility complex (MHC) restriction exists
      between hematopoietic stem cells (HSCs) and stromal cells. We transplanted bone
      marrow cells (BMCs) and bones obtained from various mouse strains and analyzed
      the cells that accumulated in the engrafted bones. Statistically significant cell
      accumulation was found in the engrafted bone, which had the same H-2 phenotype as
      that of the BMCs, whereas only few cells were detected in the engrafted bones of
      the third-party H-2 phenotypes during the 4 to 6 weeks after BMT. Moreover, the
      BMCs obtained from the MHC-compatible bone showed significant numbers of both
      colony-forming units in culture (CFU-C) and spleen colony-forming units (CFU-S).
      These findings strongly suggest that an MHC restriction exists between HSCs and
      stromal cells.

PMID- 8978278
TI  - Cytokine receptor expression on hematopoietic stem and progenitor cells.
AB  - Hematopoietic stem and progenitor cell populations were obtained by fluorescence
      activated cell sorting of murine bone marrow (BM) cells into Rhodamine-123io
      lineage-Ly6A/ E+ c-kit+ (primitive stem cells highly enriched for long-term BM
      repopulating activity), Rhodamine-123med/hl lineage- Ly6A/E+ c-kit+ (mature stem
      cells highly enriched for shortterm BM repopulating activity and day 13 spleen
      colony-forming activity) and lineage- Ly6A/E- c-kit+ (enriched for in vitro
      colony forming cells) populations. Neither stem cell population responds to
      single cytokines in vitro and each requires the synergistic action of two or more
      cytokines for proliferation, whereas the progenitor cell population proliferates
      in response to single cytokines. Since each of these cell populations was sorted
      as c-kit+, they express receptors for stem cell factor. Cell populations were
      also analyzed by autoradiography for their ability to specifically bind iodinated
      cytokines and this revealed that both stem cell populations expressed receptors
      for interleukin-1 alpha (IL-1 alpha), IL-3, IL-6, and granulocyte colony
      stimulating factor (G-CSF), but lacked receptors for macrophage colony
      stimulating factor (M-CSF), granulocyte-macrophage colony stimulating factor (GM
      CSF), and leukemia inhibitory factor (LIF). Cells within the progenitor cell
      population specifically bound IL-3, GM-CSF, G-CSF, IL-6, and IL-1 alpha, whereas
      no receptors were detected for M-CSF and LIF. Within each cell population
      examined, heterogeneity was observed in the percentage of cells labeled and the
      number of receptors per cell. These results suggest that stem cell populations
      can be further subdivided according to their cytokine receptor profile and it
      will be of interest to determine if such subpopulations have distinctive
      functional properties.

PMID- 8978277
TI  - Erythropoietin activates Raf1 by an Shc-independent pathway in CTLL-EPO-R cells.
AB  - Stimulation of the erythropoietin receptor (EPO-R) or the interleukin-2 receptor
      (IL-2-R) by their respective ligands has been reported to activate tyrosine
      phosphorylation of the cytoplasmic protein, Shc. We have recently characterized a
      cell line, CTLL-EPO-R, that contains functional cell-surface receptors for both
      EPO and IL-2. Although stimulation with IL-2 or IL-15 resulted in the rapid, dose
      dependent tyrosine phosphorylation of Shc, stimulation with EPO failed to
      activate Shc. EPO, IL-2, and IL-15 activated the tyrosine phosphorylation of the
      adaptor protein, Shp2, and the association of Shp2/Grb2/cytokine receptor
      complexes. In addition, EPO, IL-2, and IL-15 activated Raf1 and ERK2,
      demonstrating that the Raf1/MEK/MAP kinase pathway was activated. These results
      indicate that multiple biochemical pathways are capable of conferring a mitogenic
      signal in CTLL-EPO-R. EPO can activate the Raf1/MEK/MAP kinase pathway via Shc
      dependent or Shc-independent pathways, and Shc activation is not required for EPO
      dependent cell growth in CTLL-EPO-R.

PMID- 8978279
TI  - Transendothelial migration of CD34+ and mature hematopoietic cells: an in vitro
      study using a human bone marrow endothelial cell line.
AB  - To study the role of bone marrow endothelial cells (BMEC) in the regulation of
      hematopoietic cell trafficking, we have designed an in vitro model of
      transendothelial migration of hematopoietic progenitor cells and their progeny.
      For these studies, we have taken advantage of a human BMEC-derived cell line
      (BMEC-1), which proliferates independent of growth factors, is contact inhibited,
      and expresses adhesion molecules similar to BMEC in vivo. BMEC-1 monolayers were
      grown to confluency on 3 microns microporous membrane inserts and placed in 6
      well tissue culture plates. Granulocytecolony stimulating factor (G-CSF)
      mobilized peripheral blood CD34+ cells were added to the BMEC-1 monolayer in the
      upper chamber of the 6-well plate. After 24 hours of coincubation, the majority
      of CD34+ cells remained nonadherent in the upper chamber, while 1.6 +/- 0.3% of
      the progenitor cells had transmigrated. Transmigrated CD34 cells expressed a
      higher level of CD38 compared with nonmigrating CD34+ cells and may therefore
      represent predominantly committed progenitor cells. Accordingly, the total
      plating efficiency of the transmigrated CD34+ cells for lineage-committed
      progenitors was higher (14.0 +/- 0.1 v 7.8% +/- 1.5%). In particular, the plating
      efficiency of transmigrated cells for erythroid progenitors was 27-fold greater
      compared with nonmigrating cells (8.0% +/- 0.8% v 0.3% +/- 0.1%) and 5.5-fold
      compared with unprocessed CD34+ cells (2.2% +/- 0.4%). While no difference in the
      expression of the beta 1-integrin very late activation antigen (VLA)-4 and beta 2
      integrin lymphocyte function-associated antigen (LFA)-1 was found, L-selectin
      expression on transmigrated CD34+ cells was lost, suggesting that shedding had
      occurred during migration. The number of transmigrated cells was reduced by
      blocking antibodies to LFA-1, while L-selectin and VLA-4 antibodies had no
      inhibitory effect. Continuous coculture of the remaining CD34+ cells in the upper
      chamber of the transwell inserts resulted in proliferation and differentiation
      into myeloid and megakaryocytic cells. While the majority of cells in the upper
      chamber comprised proliferating myeloid precursors such as promyelocytes and
      myelocytes, only mature monocytes and granulocytes were detected in the lower
      chamber. In conclusion, BMEC-1 cells support transmigration of hematopoietic
      progenitors and mature hematopoietic cells. Therefore, this model may be used to
      study mechanisms involved in mobilization and homing of CD34+ cells during
      peripheral blood progenitor cell transplantation and trafficking of mature
      hematopoietic cells.

PMID- 8978280
TI  - Arachidonic acid mediates interferon-gamma-induced sphingomyelin hydrolysis and
      monocytic marker expression in HL-60 cell line.
AB  - The biochemical signaling mechanisms involved in transducing the effects of
      interferon-gamma (IFN-gamma) on human leukemia-derived HL-60 cell differentiation
      are not completely understood. Recent studies established the existence of a
      sphingomyelin (SM) cycle that operates in response to the action of IFN-gamma on
      HL-60 cells, but the mechanisms by which IFN-gamma induces the SM hydrolysis
      remain unexplored. In this study, biochemical events mediating IFN-gamma effects
      on SM turnover and their specificity and role in HL-60 differentiation were
      investigated. The activation of the SM cycle by IFN-gamma occurred rapidly, with
      a decrease of approximately 20% in the SM level observed after 60 minutes with a
      concomitant increase in ceramide level. Treatment of HL-60 cells with IFN-gamma
      did not influence the 1,2-diacylglycerol concentration, intracellular Ca2+
      concentration, or phospholipase D activity. IFN-gamma stimulated a rapid release
      of arachidonic acid (AA) from HL-60 cells; the effect was abolished by the
      pretreatment of cells with pertussis toxin, suggesting a role for a pertussis
      toxin-sensitive G protein in IFN-gamma-mediated activation of phospholipase A2
      (PLA2). At 4 to 120 hours after the stimulation of the cells with IFN-gamma, a
      significant increase in the particulate and soluble PLA2 activity was observed,
      corresponding to an increase in the level of immunoreactive cPLA2 in both cytosol
      and membrane fractions. The treatment of cells with tyrosine kinase inhibitor
      herbimycin A completely abolished the effect of IFN-gamma on PLA2 activity in
      membrane and cytosolic fractions, but had no effect on IFN-gamma-mediated early
      AA release suggesting dual mechanism of PLA2 activation. Melittin, potent
      activator of PLA2, and AA mimicked the effect of IFN-gamma on SM hydrolysis.
      Pretreatment of HL-60 cells with the PLA2 inhibitor, bromophenacyl bromide (BPB),
      or pertussis toxin abolished the effect of IFN-gamma on SM hydrolysis; exogenous
      addition of AA overcame the effects of BPB and pertussis toxin. Long-term
      exposure (5 days) of HL-60 cells to IFN-gamma caused an increase in nitroblue
      tetrazolium (NBT)-reducing and nonspecific esterase (NSE) activity and induced
      expression of Fc gamma RI (CD64) without significant effects on cell number,
      adherence, or phagocytic activity. The treatment of cells with AA or melittin
      induced NBT, NSE, and CD64 expression to the level similar to that observed with
      IFN-gamma, and no further increase was observed with the combination of IFN-gamma
      and AA or IFN-gamma and melittin. Treatment of HL-60 cells with indomethacin, an
      inhibitor of cyclo-oxygenase, and nordihydroguaiaretic acid (NDGA), an inhibitor
      of lipoxygenase, had no effects on IFN-gamma-mediated induction of CD64
      expression. These studies indicate a key role for the phospholipase A2/AA
      pathway, as an early biochemical signal elicited by the occupation of IFN-gamma
      receptor, in mediating IFN-gamma induction of the SM cycle and phenotypic changes
      associated with differentiation of HL-60 along monocytic lineage.

PMID- 8978281
TI  - Modulation of calcium channels in human erythroblasts by erythropoietin.
AB  - Erythropoietin (Epo) induces a dose-dependent increase in intracellular free Ca2+
      ([Ca2+]i) in human erythroblasts, which is dependent on extracellular Ca2+ and
      blocked by high doses of nifedipine or Ni2+. In addition, pretreatment of human
      erythroblasts with mouse antihuman erythropoietin receptor antibody but not mouse
      immunopure IgG blocked the Epo-induced [Ca2+]i increase, indicating the
      specificity of the Ca2+ response to Epo stimulation. In this study, the
      erythropoietin-regulated calcium channel was identified by single channel
      recordings. Use of conventional whole cell patch-clamp failed to detect Epo
      induced whole cell Ca2+ current. To minimize washout of cytosolic constituents,
      we next used nystatin perforated patch, but did not find any Epo-induced whole
      cell Ca2+ current. Using Ba2+ (30 mmol/L) as charge carrier in cell-attached
      patches, we detected single channels with unitary conductance of 3.2 pS, reversal
      potential of +72 mV, and whose unitary current (at +10 mV) increased
      monotonically with increasing Ba2+ concentrations. Channel open probability did
      not appreciably change over the voltage range (-50 to +30 mV) tested. Epo (2
      U/mL) increased both mean open time (from 4.27 +/- 0.75 to 11.15 +/- 1.80 ms) and
      open probability (from 0.26 +/- 0.06 to 2.56 +/- 0.59%) of this Ba(2+)-permeable
      channel. Our data strongly support the conclusion that the Epo-induced [Ca2+]i
      increase in human erythroblasts is mediated via Ca2+ entry through a voltage
      independent Ca2+ channel.

PMID- 8978282
TI  - Localization and regulation of thrombopoietin mRNa expression in human kidney,
      liver, bone marrow, and spleen using in situ hybridization.
AB  - Thrombopoietin (TPO) is the primary hematopoietic growth factor involved in the
      regulation of platelet production. Although the kidney, liver, bone marrow (BM),
      and spleen have been identified as the major sources of TPO production, the
      precise cellular location of TPO mRNA expression in these tissues remains
      unknown. We have identified the cells expressing TPO mRNA in the human kidney,
      liver, and BM using an in situ hybridization assay. In the BM of individuals with
      normal platelet counts, the hybridization signal was too weak to allow
      identification of the TPO mRNA expressing cells. However, in thrombocytopenic
      subjects with aplastic anemia, postchemotherapy marrow aplasia, and immune
      thrombocytopenia, the stromal cells showed strong TPO mRNA expression. In the
      human subjects with normal platelet counts, the cells of the proximal convoluted
      tubules of the kidney showed consistent positive staining whereas the signal in
      the cells of the distal convoluted tubules was less consistent. Strong
      hybridization signal was also evident in the hepatocytes. The hybridization
      signal in the spleen, even in thrombocytopenic subjects, was too weak to allow
      confident identification of the cells expressing TPO mRNA. In all subjects, the
      interstitial cells and endothelial cells of the liver and spleen, the renal
      peritubular cells, and the hematopoietic precursor cells of the BM showed no TPO
      mRNA expression. Our data suggest that TPO mRNA expression in the human BM may be
      modulated by platelet mass.

PMID- 8978283
TI  - Identification of a serpin specifically expressed in multipotent and bipotent
      hematopoietic progenitor cells and in activated T cells.
AB  - We have identified a gene that has a high level of mRNA expression in
      undifferentiated, multipotential hematopoietic cells (FDCP-Mix) and that
      downregulates both transcript and protein, as these cells are induced to
      differentiate into mature myeloid cells. Sequence analysis of this gene has
      identified it as a serine protease inhibitor EB22/3 (serpin 2A). Constitutive
      expression of serpin 2A in FDCP-Mix cells was associated with an increase in the
      clonogenic potential of the cells and with a delay in the appearance of fully
      mature cells in cultures undergoing granulocyte macrophage differentiation when
      compared with control cells. Serpin 2A was also found to be expressed in bone
      marrow-derived bipotent granulocyte macrophage progenitor cells (GM-colony
      forming cell [CFC]), but not in erythrocyte progenitor cells from day 15 fetal
      liver. Expression of serpin 2A also showed a marked up regulation during the
      activation of cytotoxic suppressor CD8+ T cells, with a clear lag between the
      appearance of transcript and detection of protein.

PMID- 8978284
TI  - A novel herpes vector for the high-efficiency transduction of normal and
      malignant human hematopoietic cells.
AB  - Herpes simplex viruses (HSVs) would offer numerous advantages as vectors for gene
      transfer, but as yet they have not proved capable of transducing hematopoietic
      cells. Using a genetically inactivated form of HSV that is restricted to a single
      cycle of replication (disabled single-cycle virus, [DISC-HSV]), we have
      transduced normal human hematopoietic progenitor cells and primary leukemia
      blasts with efficiencies ranging from 80% to 100%, in the absence of growth
      factors or stromal support. Toxicity was low, with 70% to 100% of cells surviving
      the transduction process. Peak expression of transferred genes occurred at 24 to
      48 hours after transduction with the DISC-HSV vector, declining to near
      background levels by 14 days. Despite this limitation, sufficient protein is
      produced by the inserted gene to permit consideration of the vector for
      applications in which transient expression is adequate. One example is the
      transfer of immunostimulatory genes, to generate leukemia immunogens. Thus,
      murine A20 leukemia cells transduced with a DISC-HSV vector encoding granulocyte
      macrophage colony-stimulating factor were able to stimulate a potent antitumor
      response in mice, even against pre-existing leukemia. The exceptional transducing
      ability of the DISC-HSV vector should therefore facilitate genetic manipulation
      of normal and malignant human hematopoietic cells for biological and clinical
      investigation.

PMID- 8978285
TI  - Clonality analysis of hematopoiesis in essential thrombocythemia: advantages of
      studying T lymphocytes and platelets.
AB  - Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by
      a sustained elevation of the platelet count in the absence of other causes of
      thrombocytosis. ET is difficult to diagnose, and the demonstration of clonal
      hematopoiesis may be of value. However, clonality analysis of hematopoietic cells
      based on the study of the X-chromosome inactivation pattern is complicated by the
      observation that some normal females present skewed lyonization. Moreover, DNA
      methylation of X-linked genes in hematopoietic cells may differ from that in
      other tissues. Appropriate controls for skewed lyonization are therefore critical
      for the study of clonality. We developed two techniques based on X-chromosome
      inactivation and polymerase chain reaction (PCR) analysis of polymorphisms, to
      study clonality in ET patients. Reverse transcriptase-PCR analysis of IDS, P55,
      and G6PD mRNAs was used to examine the different hematopoietic cell lineages
      including platelets in patients heterozygous for these polymorphisms and analysis
      of the HUMARA gene methylation pattern permitted us to study clonality in all
      nucleated cell fractions of the other patients. Using both types of assay and T
      lymphocytes as a control tissue for lyonization, clonal hematopoiesis was
      demonstrated in 28 patients. In 14 patients, the granulocytes were polyclonal;
      among these patients, platelets were monoclonal in 3 cases, polyclonal in 7
      cases, and in the remaining 4 cases this fraction could not be studied because
      the patients were homozygotes for all RNA markers. No conclusion about clonality
      could be drawn in 6 cases. Polyclonal hematopoiesis was found in all the cases of
      reactive thrombocytosis. These findings confirm the high frequency of monoclonal
      hematopoiesis in ET, the utility of studying platelets, and the possibility of
      using T lymphocytes as a control tissues for X-chromosome inactivation patterns.

PMID- 8978286
TI  - Antisense inhibition of c-fes proto-oncogene blocks PMA-induced macrophage
      differentiation in HL60 and in FDC-P1/MAC-11 cells.
AB  - To gain some insight into the role of c-fes in macrophage differentiation, we
      have analyzed the ability of HL60 leukemic promyelocytic cells and FDC-P1/MAC-11
      murine myeloid precursor cells to differentiate in response to phorbol esters
      after inhibition of c-fes function. Fes inactivation has been obtained by using
      oligodeoxynucleotides (ODN) complementary to the 5' region of c-fes mRNA and to
      5' splice junctions of c-fes primary transcript. After 5 days (d) in culture, in
      several separate experiments performed with different ODN preparations, a
      complete inhibition of c-fes expression was observed in HL60 and in FDC-P1/MAC-11
      cells. No perturbation of cell growth was evident in our experimental conditions
      in both cell lines after c-fes inhibition. Furthermore, in HL60 cells lacking c
      fes product, an almost complete downregulation of the alpha 4 beta 1 fibronectin
      receptor occurred. However, in both cell lines, the induction of macrophage
      differentiation by phorbol esters resulted in an almost complete maturation
      arrest as evaluated by morphological, cytochemical, immunological criteria, and
      by the cytofluorimetric cell cycle analysis. A loss of the adhesion capacity of
      both myeloid cell lines, when compared to terminally differentiated macrophages,
      was also observed. These results suggest that HL60 and FDC-P1/MAC-11 cells, when
      treated with phorbol 12-myristate 13-acetate, require c-fes protein expression to
      activate the genetic program underlying macrophage differentiation.

PMID- 8978287
TI  - Cytokine prestimulation as a gene therapy strategy: implications for using the
      MDR1 gene as a dominant selectable marker.
AB  - A major obstacle to stem cell gene therapy is the extremely low efficiency of
      stem cell transduction. In vivo selection is a strategy for enriching a minor
      population of genetically modified bone marrow cells through the introduction of
      a drug resistance gene, followed by subsequent administration of the
      corresponding cytotoxic drug in vivo. Achieving persistent effects from in vivo
      selection is expected to require selection at the level of stem cells or,
      minimally, selection at the level of progenitors. Major limitations to in vivo
      selection are the nonhematologic toxicities of the cytotoxic drugs used and the
      resistance of stem cells and progenitors to killing by most cytotoxic agents.
      Experiments were performed in mice to evaluate whether the drugs used for
      selection in combination with multiple drug resistance gene 1 (MDR1) could have
      an enhanced effect on clonogenic progenitors if preceded by administration of the
      cytokine, stem cell factor (SCF). Single doses of taxol, navelbine, or
      vinblastine produced 10-fold reductions in the total number of mononuclear cells
      per femur, indicating a significant depletion of nonclonogenic precursor cells.
      However, for each of these agents, clonogenic progenitors, assayed as colony
      forming unit cells and day-12 spleen colony-forming units, were relatively
      spared. Administration of SCF before taxol, navelbine, or vinblastine completely
      abrogated the progenitor-sparing phenomenon, because clonogenic progenitors were
      depleted as effectively as nonclonogenic precursor cells. Furthermore, the
      administration of SCF before drug administration allowed the dosages of taxol and
      vinblastine to be reduced by more than half, while retaining reductions in
      progenitor numbers that were unachievable using very high doses of the cytotoxic
      drug alone. Doxorubicin administration resulted in a 30- to 40-fold depletion in
      progenitors that was not significantly altered by preceding SCF administration.
      These results suggest that previous observations of in vivo selection using MDR1
      gene transfer followed by taxol administration may have resulted from selection
      at the level of relatively mature, nonclonogenic precursor cells. Furthermore,
      these data suggest that cytokine prestimulation may be a useful strategy for
      improving the selection of drug-resistant clonogenic progenitors and, possibly,
      stem cells in vivo.

PMID- 8978288
TI  - Prevention of thrombocytopenia and neutropenia in a nonhuman primate model of
      marrow suppressive chemotherapy by combining pegylated recombinant human
      megakaryocyte growth and development factor and recombinant human granulocyte
      colony-stimulating factor.
AB  - This report examines the effects on hematopoietic regeneration of pegylated
      recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) (2.5
      micrograms/ kg/d) alone and in combination with recombinant human granulocyte
      colony stimulating factor (rHu-GCSF) (10 micrograms/ kg/d) for 21 days in rhesus
      macaques receiving intense marrow suppression produced by single bolus injections
      of hepsulfam (1.5 g/m2). In six hepsulfam-only control animals thrombocytopenia
      (platelet count < 100 x 10(9)/L) was observed between days 12 and 25 (nadir 39 +/
      20 x 10(9)/L on day 17), and neutropenia (absolute neutrophil count < 1 x
      10(9)/L) occurred between days 8 and 30 (nadir 0.167 +/- 0.120 x 10(9)/L on day
      15). PEG-rHuMGDF (2.5 micrograms/kg/d) injected subcutaneously into four animals
      from day 1 to day 22 following hepsulfam administration produced trough serum
      concentrations of 1.9 +/- 0.2 ng/mL and increased the platelet count twofold over
      basal prechemotherapy levels (856 +/- 594 x 10(9)/L v baseline of 416 +/- 88 x
      10(9)/L; P = .01). PEG-rHuMGDF alone also shortened the period of posthepsulfam
      neutropenia from 22 days to 12 days (P = .01), although the neutropenic nadir was
      not significantly altered (neutrophil count 0.224 +/- 0.112 x 10(9)/L v 0.167 +/-
      0.120 x 10(9)/L; P > .3). rHu-GCSF (10 micrograms/kg/d) injected subcutaneously
      into four animals from day 1 to day 22 following hepsulfam administration
      produced trough serum concentrations of 1.4 +/- 1.1 ng/mL, and reduced the time
      for the postchemotherapy neutrophil count to attain 1 x 10(9)/L from 22 days to 4
      days (P = .005). The postchemotherapy neutropenic nadir was 0.554 +/- 0.490 x
      10(9)neutrophils/L (P = .3 v hepsulfam-only control of 0.167 +/- 0.120 x
      10(9)/L). However, thrombocytopenia of < 100 x 10(9) platelets/L was not
      shortened (persisted from day 12 to day 25), or less severe (nadir of 56 +/- 32 x
      10(9) platelets/L on day 14; P = .7 compared with untreated hepsulfam animals).
      The concurrent administration of rHu-GCSF (10 micrograms/kg/d) and PEG-rHuMGDF
      (2.5 micrograms/kg/d) in four animals resulted in postchemotherapy peripheral
      platelet counts of 127 +/- 85 x 10(9)/L (P = .03 compared with 39 +/- 20 x
      10(9)/L for untreated hepsulfam alone, and P = .02 compared with 856 +/- 594 x
      10(9)/L for PEG-rHuMGDF alone), and shortened the period of neutropenia < 1 x
      10(9)/L from 22 days to 4 days (P = .8 compared with rHu-GCSF alone). Increasing
      PEG-rHuMGDF to 10 micrograms/kg/d and maintaining the 21-day schedule of
      coadministration with rHu-GCSF (10 micrograms/kg/d) in another four animals
      produced postchemotherapy platelet counts of 509 +/- 459 x 10(9)/L (P < 10(-4)
      compared with untreated hepsulfam alone, and P = .04 compared with 2.5
      micrograms/kg/d PEG-rHuMGDF alone), and 4 days of neutropenia. Coadministration
      of rHu-GCSF and PEG-rHuMGDF did not significantly alter the pharmacokinetics of
      either agent. The administration of PEG-rHuMGDF (2.5 micrograms/kg/d) from day 1
      through day 22 and rHu-GCSF (10 micrograms/kg/d) from day 8 through day 22 in six
      animals produced peak postchemotherapy platelet counts of 747 +/- 317 x 10(9)/L(P
      < 10(-4) compared with untreated hepsulfam alone, and P = .7 compared with PEG
      rHuMGDF alone), and maintained the neutrophil count > 3.5 x 10(9)/L (P = .008 v
      rHu-GCSF therapy alone). Thus, both thrombocytopenia and neutropenia are
      eliminated by initiating daily PEG-rHuMGDF therapy on day 1 and subsequently
      adding daily rHu-GCSF after 1 week in the rhesus model of hepsulfam marrow
      suppression. This improvement in platelet and neutrophil responses by delaying
      the addition of rHu-GCSF to PEG-rHuMGDF therapy demonstrates the importance of
      optimizing the dose and schedule of cytokine combinations after severe
      myelosuppressive chemotherap

PMID- 8978289
TI  - Platelet and fibrin deposition at the damaged vessel wall: cooperative substrates
      for neutrophil adhesion under flow conditions.
AB  - At sites of vessel wall damage, the primary hemostatic reaction involves platelet
      and fibrin deposition. At these sites, circulating leukocytes marginate and
      become activated. Adhered platelets can support leukocyte localization; however,
      the role of fibrin in this respect is not known. We studied the adhesion of human
      neutrophils (polymorphonuclear leukocytes [PMNs]) to endothelial extracellular
      matrix (ECM)-bound fibrin and platelets under flow conditions. ECM alone did not
      show PMN adhesion. ECM-coated cover slips were perfused with plasma to form a
      surface-bound fibrin network, and/or with whole blood to allow platelet adhesion.
      Unstimulated PMNs adhered to fibrin at moderate shear stress (20 to 200 mPa). ECM
      bound platelets induced rolling adhesion and allowed more PMNs to adhere at
      higher shear (320 mPa). ECM coated with both platelets and fibrin induced more
      static and shear-resistant PMN adhesion. PMN adhesion to fibrin alone but not to
      platelet/fibrin surfaces was inhibited by soluble fibrinogen. Adhesion to fibrin
      alone was inhibited by CD11b and CD18 blocking antibodies. Furthermore, fibrin
      formed under flow conditions showed up to threefold higher PMN adhesion compared
      with fibrin formed under static conditions, due to structural differences. These
      results indicate that circulating PMNs adhere to fibrin in an integrin-dependent
      manner at moderate shear stresses. However, at higher shear rates (> 200 mPa),
      additional mechanisms (ie, activated platelets) are necessary for an interaction
      of PMNs with a fibrin network.

PMID- 8978290
TI  - Severe factor VII deficiency due to a mutation disrupting a hepatocyte nuclear
      factor 4 binding site in the factor VII promoter.
AB  - Although small deletions, splice site abnormalities, missense, and nonsense
      mutations have been identified in patients with factor VII deficiency, there have
      been no reports of mutations in the factor VII promoter. We investigated a girl
      with factor VII levels that were less than 1% of normal in association with a
      severe bleeding diathesis. The patient is homozygous for a T to G transversion
      that occurs 61 bp before the translation start site. This nucleotide is in a
      sequence that is an hepatocyte nuclear factor 4 (HNF-4) binding site within the
      factor VII promoter (ACTTTG AE-->ACGTTG). Using gel mobility shift assays, we
      show that the mutation disrupts the binding of HNF-4 to its cognate binding site.
      In growth hormone reporter gene assays, the activity of a plasmid containing the
      mutant promoter was 6.7% of the wild-type promoter plasmid. Although HNF-4 was
      able to transactivate the wild-type factor VII promoter 5.4-fold in HeLa cells,
      no transactivation could be shown with the mutant promoter. These findings
      indicate that HNF-4 exerts a major positive regulatory effect on factor VII
      expression and provides in vivo evidence that binding of this transcription
      factor is critical for normal factor VII expression.

PMID- 8978291
TI  - Molecular pathogenesis of type I congenital plasminogen deficiency: expression of
      recombinant human mutant plasminogens in mammalian cells.
AB  - We previously reported the genetic abnormality in a Japanese family with type I
      congenital plasminogen deficiency caused by a Ser572 to Pro572 mutation. To
      characterize the molecular pathogenesis of the disease in this family, we
      expressed recombinant human wild-type and mutant (rS572P) plasminogens in COS-1
      cells. Activation-resistant wild-type and mutant plasminogen stable transfectants
      in CHO-K1 cells also were established. Transient transfection and metabolic
      labeling experiments followed by immunoprecipitation analysis showed that the
      mutant plasminogen was secreted from COS-1 cells in reduced amounts, compared
      with the wild type. Endo H digestion of the wild-type and mutant plasminogen
      showed no shift in their migrations on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis, indicating that both contain complex type
      oligosaccharide structures and could therefore be secreted. Furthermore, the
      secretion of activation-resistant mutant plasminogen was significantly reduced.
      Pulse-chase experiments and Northern blot analysis showed that the impaired
      secretion of the mutant plasminogen was the consequence of the accumulation of
      the mutant protein inside the cells but not of reduced plasminogen mRNA.
      Immunocytochemical staining of stable transfectants also revealed that CHO-K1
      cells expressing the activation-resistant mutant plasminogen stained mainly in
      the perinuclear area, suggesting delayed processing of the mutant protein in the
      intracellular transport pathway. We conclude that the impaired secretion of
      mutant plasminogen, due to intracellular accumulation, is the molecular
      pathogenesis of type I congenital plasminogen deficiency caused by a Ser572 to
      Pro572 mutation.

PMID- 8978292
TI  - Hemophilia and nonprogressing human immunodeficiency virus type 1 infection.
AB  - Seven of 112 hemophiliacs infected with human immunodeficiency virus type-1 (HIV
      1) before 1986 through contaminated plasma products are currently healthy, with
      CD4 T-cell counts above 500 cells/microL, and have never received antiretroviral
      therapy (long-term nonprogressors [LTNPs]). Seven age and sex-matched
      hemophiliacs infected in the same period but who have progressive HIV disease
      (progressors) and one additional slow-progressing individual were also studied.
      One hundred-fold, 20-fold, and 10-fold lower levels of full-length HIV RNA in
      plasma, peripheral blood mononuclear cells (PBMCs), and proviral DNA in PBMCs,
      respectively, were found in LTNPs compared with progressors. Plasma and cell
      associated HIV RNA and proviral DNA were lower in LTNPs who tested negative for
      viral isolation from PBMCs or who were positive only after removal of CD8+ cells.
      No substantial differences were observed in the in vitro production of chemokines
      including RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and interleukin-8 (IL-8) in
      supernatants of activated PBMCs or CD8-depleted PBMCs of LTNPs, even when HIV
      isolation was simultaneously accomplished exclusively after removal of CD8+
      cells. Low levels of HIV load and replication in peripheral blood are the
      strongest correlates of nonprogression in this small number of infected
      hemophiliacs.

PMID- 8978293
TI  - Interleukin-15 triggers the proliferation and cytotoxicity of granular
      lymphocytes in patients with lymphoproliferative disease of granular lymphocytes.
AB  - The recently cloned cytokine interleukin-15 (IL-15) shares several functional
      activities with IL-2 in different cell systems. Although IL-15 does not show
      sequence homology with IL-2, it uses components of the IL-2 receptor (IL-2R) for
      binding and signal transduction, namely, p75 (beta) and the p64 (gamma) chains of
      IL-2R. To evaluate whether IL-15 is involved in the activation of granular
      lymphocytes (GL) in patients with lymphoproliferative disease of granular
      lymphocytes (LDGL), we evaluated the ability of IL-15 to stimulate GL
      proliferation, cytotoxic function, and the role of IL-2R beta and gamma molecules
      on relevant cells. Our results show that IL-15 stimulates cell proliferation and
      cytotoxic activity of GL in LDGL patients. Reverse-transcriptase polymerase chain
      reaction (RT-PCR) and phenotypic analyses using the anti-IL-2R gamma-chain
      specific TUGh4 monoclonal antibody (MoAb) indicate that both CD3+ and CD3- GL
      express the p64 IL-2R, a result previously unknown. IL-15 activity was inhibited
      by antibodies against p75 and p64 IL-2R chains, while no inhibitory effects are
      detectable with anti-p55 IL-2R antibody. The association of anti-p75 and anti-p64
      IL-2R MoAbs resulted in a nearly complete (95%) inhibition of IL-15-induced GL
      proliferation. Using RT-PCR analysis, we demonstrated that highly purified CD3+
      and CD3- GL did not express mRNA for IL-15 or IL-2. By contrast, a clear-cut IL
      15 mRNA signal was detected by RT-PCR in patients' peripheral blood mononuclear
      cells, with monocytes likely accounting for the source of IL-15 in LDGL patients.
      However, even in concentrated supernatants from enriched monocyte populations, we
      could not demonstrate the presence of IL-15 protein. Using anti-IL-15 specific
      MoAbs, a membrane-bound form of this cytokine was demonstrated both on CD3+ and
      CD3- LDGL cells. By RT-PCR analysis, purified GL from these patients were found
      to express the message for IL-15 receptor alpha chain. Taken together, these
      results indicate that both CD3+ and CD3- GL are stimulated by IL-15 and that this
      cytokine mediates its activity through the beta and gamma chains of the IL-2R,
      providing further suggestions for the interpretation of the mechanisms that lead
      to cell expansion in patients with LDGL.

PMID- 8978294
TI  - Transfer of the interleukin-2 gene into human cancer cells induces specific
      antitumor recognition and restores the expression of CD3/T-cell receptor
      associated signal transduction molecules.
AB  - Normal peripheral blood mononuclear cells (PBMC) were co-cultured with a human
      lung cancer cell line (LC89) transduced with the interleukin-2 (IL-2), IL-7,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis
      factor-alpha (TNF-alpha) genes to evaluate the capacity of the engineered cells
      to: allow survival of CD3+ and CD56+ cells, generate cytotoxic effectors with HLA
      class I restricted and unrestricted antitumor activity, and interfere in the
      molecular organization of the CD3/T-cell receptor associated signal transduction
      machinery. When PBMC were cultured up to 3 weeks with IL-2 releasing LC89 cells
      (LC89/IL-2), the number of viable CD3+ and CD56+ lymphocytes was much greater
      than in cultures with parental cells or with LC89 cells transduced with the other
      cytokine genes. After 1 week of coculture, a variable degree of restricted and
      unrestricted killing directed against different targets was observed. When the
      cultures were prolonged up to 3 weeks, LC89/IL-2 cells induced a marked increase
      in specific cytotoxic activity, which was coupled to a further enhancement of
      unrestricted lytic function. In the presence of LC89/IL-7 cells the degree of
      specific lysis remained unchanged, whereas unrestricted effectors were markedly
      decreased. No cytotoxic activity could be induced by LC89/GM-CSF and LC89/TNF
      alpha cells in the few lymphocytes surviving after 3 weeks of culture. Coculture
      of parental LC89 cells with PBMC was consistently associated with a
      downmodulation in the expression of the CD3 zeta chain, as well as of the
      tyrosine kinases p56ick and ZAP-70. On the contrary, LC89/IL-2 cells, and not
      LC89 cells transduced with the IL-7, GM-CSF, or TNF-alpha gene, were capable of
      reverting the immunosuppressive effect exerted by the tumor cells. This
      protective effect could be maintained in cultures prolonged up to 4 weeks. When
      the same cultures were set up in Transwell, ie, with a membrane separation
      between cancer cells and PBMC, the expression of the CD3 zeta chain and of the
      p56ick and ZAP-70 tyrosine kinases remained unchanged under all culture
      conditions, indicating that the downmodulation of T-cell signal transduction
      molecules requires a direct cell to cell contact. These results show that
      transfer of the IL-2 gene into the DNA of human cancer cells promotes both
      restricted and unrestricted antitumor activity, and is capable of restoring and
      maintaining the expression of molecules involved in the process of T-cell
      mediated tumor cell recognition, thus underlining the potential role of the IL-2
      gene in the design of vaccination protocols with cytokine gene transduced cancer
      cells.

PMID- 8978295
TI  - Myeloma VL and VH gene sequences reveal a complementary imprint of antigen
      selection in tumor cells.
AB  - In multiple myeloma, sequence studies of VH genes used to encode clonal Ig in
      neoplastic plasma cells have shown a common pattern of extensive somatic
      hypermutation. A further consistent feature of these VH sequences is a complete
      lack of intraclonal variation. These findings indicate that the malignant cell
      arises at a mature, postfollicular stage of B-cell development. However, only a
      minority of cases have a distribution of somatic mutations in VH consistent with
      a prior role for antigen in selecting the B cell of origin. To complement these
      studies, and to take further the investigation of a role for antigen in the
      clonal history of myeloma, we have investigated tumor-derived VL sequences from
      bone marrows of 15 patients. All sequences (9V kappa and 6V lambda A) were
      potentially functional and 5 of 15 had evidence for N-region additions. All had
      undergone extensive somatic hypermutation, and showed no intraclonal variation.
      In 4 of 15 cases, the distribution of mutations revealed a significant (P < .05)
      clustering of replacement mutations in the CDR sequences, indicating a role for
      VL in selection by antigen. Comparison with the VH sequences used by the same
      tumor cells showed that, if significant clustering was present, it was in either
      VH or VL but not both. Altogether, 10 of 15 V-regions showed evidence for antigen
      selection, suggesting that the B cell of origin has behaved as a normal germinal
      center B cell. Deductions concerning a role for antigen selection may require
      both VH and VL sequences for validation.

PMID- 8978296
TI  - Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase
      activation in multiple myeloma cells.
AB  - Fas belongs to the family of type-1 membrane proteins that transduce apoptotic
      signals. In the present studies, we characterized signaling during Fas-induced
      apoptosis in RPMI-8226 and IM-9 multiple myeloma (MM) derived cell lines as well
      as patient plasma cell leukemia cells. Treatment with anti-Fas (7C11) monoclonal
      antibody (MoAb) induced apoptosis, evidenced by internucleosomal DNA
      fragmentation and propidium iodide staining, and was associated with increased
      expression of c-jun early response gene. We also show that anti-Fas MoAb
      treatment is associated with activation of stress-activated protein kinase (SAPK)
      and p38 mitogen-activated protein kinase (MAPK); however, no detectable increase
      in extracellular signal-regulated kinases (ERK1 and ERK2) activity was observed.
      Because interleukin-6 (IL-6) is a growth factor for MM cells and inhibits
      apoptosis induced by dexamethasone and serum starvation, we examined whether IL-6
      affects anti-Fas MoAb-induced apoptosis and activation of SAPK or p38 MAPK in MM
      cells. Culture of MM cells with IL-6 before treatment with anti-Fas MoAb
      significantly reduced both DNA fragmentation and activation of SAPK, without
      altering induction of p38 MAPK activity. These results therefore suggest that
      anti-Fas MoAb-induced apoptosis in MM cells is associated with activation of
      SAPK, and that IL-6 may both inhibit apoptosis and modulate SAPK activity.

PMID- 8978297
TI  - Antibodies to transcobalamin II block in vitro proliferation of leukemic cells.
AB  - The plasma protein transcobalamin II (TCII) binds and delivers cobalamin (Cbl;
      vitamin B12) to all cells, which internalize the TCII/Cbl complex by receptor
      mediated endocytosis. Congenital deficiency of TCII results in intracellular Cbl
      deficiency, one effect of which is to disrupt DNA synthesis, leading to
      megaloblastic anemia. We report here an in vitro culture system in which cell
      growth is dependent on delivery of Cbl to cells by TCII. Recombinant human holo
      TCII was shown to support in dose-dependent manner the growth of the human
      erythroleukemic cell line K562 and the murine lymphoma cell line BW5147. Free Cbl
      also supported cell growth; however, at 100- to 1,000-fold higher concentrations
      than those effective in the presence of apo-TCII. To determine if cellular
      depletion of Cbl could be achieved by interfering with interactions between
      TCII/Cbl and its cell-surface receptor, several monoclonal antibodies raised
      against human TCII were studied. Three antibodies, found to compete for the same
      binding site on TCII, proved to be effective inhibitors of TCII/Cbl-dependent
      cell growth. Our results suggest that monoclonal anti-TCII antibodies that block
      the function of this protein may prove useful in antitumor therapies.

PMID- 8978298
TI  - Measurement of spontaneous and therapeutic agent-induced apoptosis with BCL-2
      protein expression in acute myeloid leukemia.
AB  - We have designed in vitro assays to investigate the possible association between
      apoptosis and chemotherapeutic sensitivity in acute myeloid leukemias (AMLs).
      Consistent low levels of spontaneous apoptosis were observed in myeloid cells
      from normal bone marrow samples, while untreated cells collected from 56 de novo
      AML patients showed variable apoptosis. Control myeloid cells showed increased
      apoptosis after in vitro treatments with daunomycin (DNR), cytosine arabinoside
      (ARA-C), or gamma irradiation (RAD). Most AML samples showed less treatment
      associated apoptosis, suggesting that apoptosis responses to therapeutic agents
      may be frequently attenuated in AML. Certain cytogenetic abnormalities common in
      AML may affect apoptosis, as acute promyelocytic leukemia (APL) samples with
      t(15;17) karyotypes showed consistently low levels of spontaneous and treatment
      associated apoptosis. Apoptosis assays may provide unique functional subtyping of
      AMLs, as other common cytogenetic subsets showed variable apoptosis. Altered
      function of two well-characterized regulators of apoptosis, BCL-2 and p53, was
      not entirely responsible for this variability. A genomic p53 mutation was found
      in only one AML sample. All samples that demonstrated the highest BCL-2-positive
      cell fractions showed low apoptosis, but reduced apoptosis was seen in both the
      presence and absence of BCL-2 overexpression. Finally, data from matched
      diagnosis and relapse sample pairs suggest that neither further reduced apoptosis
      nor additional BCL-2 overexpression is necessarily associated with disease
      progression.

PMID- 8978299
TI  - The lymphoproliferative disease of granular lymphocytes: updated criteria for
      diagnosis.
AB  - The lymphoproliferative disease of granular lymphocytes (LDGL), also referred to
      as LGL leukemia, is a heterogeneous disorder, but is clinically, morphologically,
      and immunologically distinct. Although LDGL has recently been included in the
      revised classification of lymphomas as an independent clinical entity, no
      consensus exists on the criteria to establish the diagnosis. The aim of this
      report was to refine the parameters needed to make the diagnosis of LDGL. We
      studied 11 patients with chronic granular lymphocytosis selected from among 195
      cases observed by our institutions from three different geographic areas (North
      America, Europe, and Asia). These cases did not meet the current criteria for
      inclusion in LDGL, since all patients had less than 2,000 GL/microL. However, in
      each of these patients, we found evidence for expansion of a discrete GL
      population. Clonal rearrangement of the T-cell receptor (TCR) beta gene was found
      in peripheral blood mononuclear cells (PBMC) of all nine patients with CD3+ LDGL.
      Using recently generated monoclonal antibodies (MoAbs) against the TCR V beta
      gene regions, we identified a unique TCR V beta on GL from each of three patients
      studied. In two patients with CD3- LDGL, we also identified a restricted pattern
      of reactivity, by staining with MoAbs against p58 antigen found on normal natural
      killer (NK) cells. The clinical features of these 11 patients with relatively low
      absolute number of GL were similar to those reported previously for patients with
      greater than 2,000 GL/microL. These data demonstrate that newer techniques such
      as MoAbs against V beta gene regions and p58 molecules and molecular analyses are
      useful to identify expansions of discrete GL proliferations. Demonstration of an
      expansion of a restricted GL subset is evidence for the diagnosis of LDGL, even
      in patients with a relatively low GL count. Our results also contribute to
      distinguish between the end of normality and the beginning of pathology in the
      broad spectrum of GL lymphocytoses.

PMID- 8978300
TI  - Interferon-beta interrupts interleukin-6-dependent signaling events in myeloma
      cells.
AB  - Type I interferons (IFNs-alpha and IFN-beta) bind to a common receptor to exert
      strong antiproliferative activity on a broad range of cell types, including
      interleukin-6 (IL-6)-dependent myeloma cells. In this study, we investigated the
      effect of IFN-beta pretreatment on IL-6-stimulated mitogenic signaling in the
      human myeloma cell line U266. IL-6 induced transient tyrosine phosphorylation of
      the IL-6-receptor signal-transducing subunit gp130, the gp130-associated protein
      tyrosine kinases Jak1,Jak2, and Tyk2, the phosphotyrosine phosphatase PTP1D/Syp,
      the adaptor protein Shc and the mitogen-activated protein kinase Erk2, and
      accumulation of GTP-bound p21ras. Prior treatment of U266 cells with IFN-beta
      downregulated IL-6-induced tyrosine phosphorylation of gp130, Jak2, PTP1D/Syp,
      Shc, and Erk2, and GTP-loading of p21ras. Further analysis indicated that
      treatment with IFN-beta disrupted IL-6-induced binding of PTP1D/Syp to gp130 and
      the adaptor protein Grb2; IFN-beta pretreatment also interfered with IL-6-induced
      interaction of Shc with Grb2 and a 145-kD tyrosine-phosphorylated protein. These
      results suggest a novel mechanism whereby type I IFNs interrupt IL-6-promoted
      mitogenesis of myeloma cells in part by preventing the formation of essential
      signaling complexes leading to p21ras activation.

PMID- 8978301
TI  - Deletions and loss of expression of p16INK4a and p21Waf1 genes are associated
      with aggressive variants of mantle cell lymphomas.
AB  - Mantle cell lymphoma (MCL) is molecularly characterized by bcl-1 rearrangement
      and cyclin D1 gene overexpression. Some aggressive variants of MCL have been
      described with blastic or large cell morphology, higher proliferative activity,
      and shorter survival. The cyclin-dependent kinase inhibitors (CDKIs) p21Waf1 and
      p16INK4a have been suggested as candidates for tumor-suppressor genes. To
      determine the role of p21Waf1 and p16INK4a gene alterations in MCLs, we examined
      the expression, deletions, and mutations of these genes in a series of 24 MCLs,
      18 typical, and 6 aggressive variants. Loss of expression and/or deletions of
      p21Waf1 and p16INK4a genes were detected in 4 (67%) aggressive MCLs but in none
      of the typical variants. Two aggressive MCLs showed a loss of p16INK4a
      expression. These cases showed homozygous deletions of p16INK4a gene by Southern
      blot analysis. An additional aggressive MCL in which expression could not be
      examined showed a hemizygous 9p12 deletion. Loss of p21Waf1 expression at both
      protein and mRNA levels was detected in an additional aggressive MCL. No p21Waf1
      gene deletions or mutations were found in this case. The p21Waf1 expression in
      MCLs was independent of p53 mutations. The two cases with p53 mutations showed
      p21Waf1 and p16INK4a expression whereas the 4 aggressive MCLs with p16INK4a and
      p21Waf1 gene alterations had a wild-type p53. p21Waf1 and p16INK4a were expressed
      at mRNA and protein levels in all typical MCLs examined. No gene deletions or
      point mutations were found in typical variants. Two typical MCLs showed an
      anomalous single-stranded conformation polymorphism corresponding to the known
      polymorphisms at codon 148 of p16INK4a gene and codon 31 of p21Waf1 gene. These
      findings indicate that p21Waf1 and p16INK4a alterations are rare in typical MCLs
      but the loss of p21Waf1 and p16INK4a expression, and deletions of p16INK4a gene
      are associated with aggressive variants of MCLs, and they occur in a subset of
      tumors with a wild-type p53 gene.

PMID- 8978302
TI  - Monoclonal origin of concordant T-cell malignancy in identical twins.
AB  - Acute leukemia has a high concordance rate in young identical twins and in
      infants this is known, from molecular analysis, to reflect an in utero origin in
      one twin followed by prenatal metastasis to the other twin via intraplacental
      anastomoses. The situation in older twins with leukemia has been less clear. We
      describe a pair of identical twins who were diagnosed with a T-cell malignancy at
      9 and 11 years of age, one with T-cell non-Hodgkin's lymphoma and the other with
      T-cell acute lymphoblastic leukemia. Leukemic cells from the twins shared the
      same TCR beta gene rearrangement with an identical 11 bp N region. The most
      plausible interpretation of this result is that these malignancies were initiated
      in one twin fetus in utero, in a single T-lineage cell that had stable bi-allelic
      TCR beta rearrangements. Progeny of this cell then spread to the other twin
      before birth via shared placental vasculature. This was then followed by a 9- and
      11-year preleukemic latent period before clinical disease manifestation as
      leukemia or lymphoma. This result has considerable implications for the etiology
      and natural history of pediatric leukemia.

PMID- 8978303
TI  - Clinical and prognostic significance of femoral marrow magnetic resonance imaging
      in patients with malignant lymphoma.
AB  - We evaluated 56 consecutive patients with newly diagnosed lymphoma including 48
      with non-Hodgkin's lymphoma (NHL) and 8 with Hodgkin's disease to determine the
      clinical and prognostic significance of magnetic resonance imaging (MRI) of the
      femoral marrow. MR images of the femoral marrow were obtained by the T1-weighted
      spin echo method and the short TI inversion recovery technique. Abnormal
      "positive" images were seen in 29 of the 56 patients (52%). All 17 patients with
      positive biopsy results showed abnormal images on their femoral marrow MRI. Three
      "positive" MRI patterns-scattered (72%), uniform (21%), and nodular (7%)-were
      observed. The overall survival of the patients with a positive MRI pattern was
      significantly poorer than that of patients with a normal pattern (P = .0129).
      Survival did not differ significantly according to MRI pattern. The 3-year
      survival rate in the patients with a normal MRI pattern was 89.9% and in the
      patients with a positive MRI pattern, it was 41.0%. This difference was
      statistically significant (P = .0279) when we evaluated only the patients with
      NHL. Patients with positive MRI patterns, but a normal bone marrow histology,
      showed a significantly shorter survival than those with a normal MRI pattern (P =
      .016). These results indicate that abnormal MR images of the femoral marrow are
      associated with a significantly poorer survival in patients with malignant
      lymphoma, regardless of histologic findings in the marrow.

PMID- 8978304
TI  - Migration of cells with immunoglobulin/c-myc recombinations in lymphoid tissues
      of mice.
AB  - Recombinations between c-myc and immunoglobulin (Ig) sequences that typically
      occur in pristane-induced mouse plasmacytomas were detected in secondary lymphoid
      tissues from normal mice, chiefly in the gut-associated lymphoid tissue. Based on
      the analysis of recombination sequences as clonotypic markers, migration of c-myc
      recombination-positive cells was observed between Peyer's patches and into the
      intestine. Treatment of plasmacytoma-susceptible BALB/cAn mice with pristane
      induced proliferation and migration of these cells into mesenteric lymph node,
      spleen, and oil granuloma within 7 days. Plasmacytoma-resistant strains of mice
      (DBA/2N, C3H/HeJ, C57BL/6) differed in that (1) they harbored fewer clones (Ig/c
      myc recombinations were detected in 33% of resistant mice versus 91% of BALB/cAn
      mice after pristane treatment); (2) Ig/c-myc-positive cells were rarely detected
      in the oil granuloma, and (3) c-myc recombined predominantly with the Ig alpha
      locus in BALB/cAn mice (72%), but with the Ig mu locus in DBA/2N and in C57BL/6
      (67%). The results demonstrate that normal mice generate a large number of
      lymphocytes with aberrant c-myc in intestinal tissues without developing tumors.

PMID- 8978305
TI  - Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation.
AB  - CRKL has previously been shown to be a major tyrosine phosphorylated protein in
      neutrophils of patients with BCR-ABL+ chronic myelogenous leukemia and in cell
      lines expressing BCR-ABL CRKL and BCR-ABL form a complex as demonstrated by
      coimmunoprecipitation and are capable of a direct interaction in a yeast two
      hybrid assay. We have mapped the site of interaction of CRKL and BCR-ABL to the
      amino terminal SH3 domain of CRKL with a proline rich region in the C-terminus of
      ABL. The proline-rich region was mutated and the effect of this deletion on BCR
      ABL transforming function was assayed. Our data show that this deletion does not
      impair the ability of BCR-ABL to render myeloid cells factor independent for
      growth. In cells expressing the proline deletion mutation of BCR-ABL, CRKL is
      still tyrosine phosphorylated and forms a complex with BCR-ABL as demonstrated by
      coimmunoprecipitation. Our data suggest that the interaction between CRKL and the
      proline deletion mutant of BCR-ABL is an indirect interaction as CRKL does not
      interact directly with the proline deletion mutant of BCR-ABL in a gel overlay
      assay or in a yeast two-hybrid assay. Thus, a direct interaction of CRKL and BCR
      ABL is not required for CRKL to become tyrosine phosphorylated by BCR-ABL and
      suggests that CRKL function may still be required for BCR-ABL function through an
      indirect interaction.

PMID- 8978306
TI  - Engagement of the Lewis X antigen (CD15) results in monocyte activation.
AB  - We previously reported that monocyte adhesion to tumor necrosis factor-alpha (TNF
      alpha)-treated endothelial cells increased expression of tissue factor and CD36
      on monocytes. Using immunological cross-linking to mimic receptor engagement by
      natural ligands, we now show that CD15 (Lewis X), a monocyte counter-receptor for
      endothelial selectins may participate in this response. We used cytokine
      production as a readout for monocyte activation and found that CD15 cross-linking
      induced TNF-alpha release from peripheral blood monocytes and cells from the
      monocytic cell line MM6. Quantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) showed an increase in steady-state TNF-alpha mRNA after 3 to 4
      hours of cross-linking. CD15 cross-linking also concomitantly increased
      interleukin-1 beta (IL-1 beta) mRNA, while no apparent change was observed in the
      levels of beta-actin mRNA, indicating specificity. To examine transcriptional
      regulation of cytokine genes by CD15 engagement, a CAT plasmid reporter construct
      containing IL-1 beta promoter/enhancer sequences was introduced into MM6.
      Subsequent cross-linking of CD15 increased CAT activity. CD15 engagement by
      monoclonal antibody also attenuated IL-1 beta transcript degradation,
      demonstrating that signaling via CD15 also had posttranscriptional effects.
      Nuclear extracts of anti-CD15 cross-linked cells demonstrated enhanced levels of
      the transcriptional factor activator protein-1, minimally changed nuclear factor
      kappa B, and did not affect SV40 promoter specific protein-1. We conclude that
      engagement of CD15 on monocytes results in monocyte activation. In addition to
      its well-recognized adhesive role, CD15 may function as an important signaling
      molecule capable of initiating proinflammatory events in monocytes that come into
      contact with activated endothelium.

PMID- 8978307
TI  - Enhancement of macrophage colony-stimulating factor-induced growth and
      differentiation of human monocytes by interleukin-10.
AB  - Interleukin-10 (IL-10) has been reported to be a negative cytokine for
      monocytes/macrophages. In the present study, we showed that IL-10 is rather a
      positive cytokine and augments the growth and differentiation of human monocytes
      stimulated with macrophage colony-stimulating factor (M-CSF). Highly purified
      adherent human monocytes were cultured for 7 days with M-CSF in the presence or
      absence of IL-10. The number of recovered cells increased in the culture of
      monocytes with M-CSF + IL-10 compared to the culture with M-CSF alone. IL-10
      alone was not enough to maintain the survival and differentiation of monocytes
      into macrophages. Morphological change cultured in M-CSF was also accelerated by
      addition of IL-10, and macrophages cultured in M-CSF + IL-10 were more elongated
      compared to macrophages cultured with M-CSF alone. Binding of 125I-M-CSF to
      monocytes incubated with M-CSF + IL-10 was about 1.7-fold higher than that to
      monocytes incubated with M-CSF alone. In accordance with the binding study,
      Northern blot analysis showed that the levels of the expression of c-fms, M-CSF
      receptor, mRNA in macrophages cultured in M-CSF + IL-10 were higher than that in
      macrophages cultured in M-CSF alone. Macrophages cultured in M-CSF + IL-10
      expressed higher level of Fc gamma RI, II, III, and showed augmented Fc gamma
      receptor mediated phagocytosis. The former also produced higher level of H2O2 and
      O2-, when stimulated with zymosan, and of IL-6 when stimulated with
      lipopolysaccharide compared to the latter. These results taken together suggest
      that IL-10 augments the growth and differentiation of human monocytes cultured in
      M-CSF.

PMID- 8978308
TI  - Erythroblastic inclusions in dominantly inherited beta thalassemias.
AB  - While the precipitation of unstable variant beta-globin chains has been
      implicated as a major pathogenic mechanism in dominantly inherited beta
      thalassemia, their instability and presence in intra-erythroblastic inclusions
      have not been conclusively shown. We report the investigation of two cases of
      dominantly inherited beta thalassemia due to heterozygosity for the beta-codon
      121 G-T mutation. In one case, we were able to demonstrate the presence of an
      abnormal beta-globin chain in both peripheral blood reticulocytes and bone marrow
      erythroblasts, and to assess its stability in relation to the substantial amounts
      of mutant beta mRNA transcript. The serum transferrin receptor (TfR) level was
      markedly increased, an indication of increased erythropoietic activity. In both
      cases, we could show by immunoelectron microscopy that the intra-erythroblastic
      inclusion bodies, a prominent feature of diseases in this category, contained not
      only precipitated alpha-globin chains, but also beta chains. The data confirm
      previous suggestions that the cellular pathology underlying this group of beta
      thalassemias is related to the synthesis of highly unstable beta-globin chain
      variants, which fail to form functional tetramers and precipitate intracellularly
      with the concomitant excess alpha chains, leading to increased ineffective
      erythropoiesis.

PMID- 8978309
TI  - Limits of the human-PBL-SCID mice model: severe restriction of the V beta T-cell
      repertoire of engrafted human T cells.
AB  - A recent study in the human-peripheral blood lymphocytes severe combined
      immunodeficiency (hu-PBL-SCID) model, analyzing the specificity of the engrafted
      human T cells, showed that human T-cell lines and clones derived from engrafted
      cells presented a xenoreactivity toward murine host molecules. This observation
      raised the question of the influence of the SCID environment on the ex vivo
      repertoire and function on the human T cells reconstituting the murine host. We
      have characterized the human V beta repertoire in the spleen of hu-PBL-SCID mice
      1 to 3 months after their engraftment. Fluorescence-activated cell sorting (FACS)
      analysis of human V beta T-cell representation showed that, for all chimeras, all
      tested V beta subsets were submitted to underrepresentation and/or expansion upon
      engraftment. Importantly, these quantitative modifications of the T-cell
      repertoire were associated with a severe restriction in both the CDR3 size
      distribution pattern of the V beta transcripts and the number of J beta segments
      used by these transcripts. In addition, ex vivo phenotypic characterization of
      engrafted cells showed that 70% to 100% expressed the activation markers HLA-DR,
      CD45RO, and CD38. Taken together, these results suggest that, following their
      engraftment, human T cells were submitted to a massive antigenic selection.
      Moreover, we found that these activated T cells were unresponsive to in vitro
      mitogenic and superantigenic activation. The consequences of the skewed
      repertoire and altered function of engrafted human T cells on the validity of
      this humanized murine model are discussed.

PMID- 8978310
TI  - Monitoring of tumor cell purging after highly efficient immunomagnetic selection
      of CD34 cells from leukapheresis products in breast cancer patients: comparison
      of immunocytochemical tumor cell staining and reverse transcriptase-polymerase
      chain reaction.
AB  - We studied the efficiency of indirect tumor cell purging via enrichment of CD34+
      hematopoietic progenitor cells from leukapheresis products (LP) in breast cancer
      patients based on immunomagnetic selection of CD34+ cells. Detection of tumor
      cells was made by immunocytochemical staining. In addition, we evaluated the
      capacity of cytokeratin 19 (CK19)- and a novel epidermal growth factor receptor
      (EGF-R)-specific reverse transcriptase-polymerase chain reaction (RT-PCR) for
      monitoring tumor cell depletion. LP from 13 breast cancer patients were analyzed.
      Twenty-three CD34 selection procedures were performed. A median of 1.4 x 10(10)
      total nucleated cells ([TNC] range, 0.88 to 3.5 x 10(10)) with a median CD34
      purity of 2.5% (range, 0.4% to 6.3%) were entered into the selection procedure.
      Immunomagnetic CD34 enrichment resulted in a median purity of 83.3% (range, 45%
      to 95.4%) and a median recovery of 73.2% (range, 22% to 95%). Retransfusion of
      CD34-selected cells after high-dose chemotherapy resulted in a rapid and
      sustained hematologic recovery, reaching an absolute neutrophil count of
      500/microL at day +10 and platelet count of 20,000/microL at day +11. Tumor cell
      depletion was quantified by immunocytochemical detection of CK19-positive cells.
      By this method, a median tumor cell depletion of 1.9 log (range, 0.7 to > 3 log)
      could be demonstrated. Immunocytochemical detection of tumor cells was more
      sensitive than RT-PCR, yielding positive results in 81% of LP (17 to 21) versus
      58% positive LP (10 of 17). However, EGF-R-based RT-PCR was much more sensitive
      than CK19-based RT-PCR (10 of 17 v 1 of 17). Despite highly efficient CD34
      selection, tumor cells were still detectable after CD34 enrichment using
      immunocytochemistry and EGF-R-specific RT-PCR. Thus, this novel EGF-R-specific RT
      PCR appears to be of value as an additional method to detect contaminating breast
      cancer cells within LP.

PMID- 8978311
TI  - Biological pattern of AML-M0 versus AML-M1: response.

PMID- 8978312
TI  - Extensive latent retroviral infection in bone marrow of patients with HTLV-I
      associated neurologic disease.

PMID- 8978313
TI  - Promyelocytic leukemia in Mexican Mestizos.

PMID- 8978314
TI  - The t(11;14) (q13;q32) in multiple myeloma cell line KMS12 has its 11q13
      breakpoint 330 kb centromeric from the cyclin D1 gene.

PMID- 8978315
TI  - Reconstitution of membrane IgD- (mIgD-) B cells after marrow transplantation lags
      behind the reconstitution of mIgD+ B cells.

PMID- 8978316
TI  - Mechanisms of coronary microvascular dilation induced by the activation of
      pertussis toxin-sensitive G proteins are vessel-size dependent. Heterogeneous
      involvement of nitric oxide pathway and ATP-sensitive K+ channels.
AB  - G proteins are critically important mediators of many signal transduction
      systems. In the present study, we investigated the effect of direct activation of
      pertussis toxin (PTX)-sensitive G protein (GPTX) on coronary arterial
      microvascular tone in 37 open-chest anesthetized dogs in vivo. Coronary arterial
      microvessels on the surface of the beating left ventricle were visualized by
      performing fluorescence coronary microangiography using an intravital microscope
      with a floating objective system. Microvessels were divided into two groups,
      small microvessels (inner diameter, < or = 130 microns) and large microvessels
      (inner diameter, > 130 microns). Topically applied mastoparan (G protein
      activator, 10, 30, and 100 mumol/L) produced homogeneous microvascular dilation
      in a concentration-dependent manner (10 mumol/L, 7.9 +/- 2.0%; 30 mumol/L, 10.3
      +/- 2.4%; and 100 mumol/L, 16.7 +/- 4.5% in small microvessels; 10 mumol/L, 5.3
      +/- 1.2%; 30 mumol/L, 9.8 +/- 2.5%; and 100 mumol/L, 15.5 +/- 3.9% in large
      microvessels). These dilations were reversed to constriction by pretreatment with
      PTX (300 ng/mL, 2 hours) in both microvessel groups. Blockade of nitric oxide
      production by NG-nitro-L-arginine (LNNA, 300 mumol/L) offset the mastoparan
      induced dilation in large microvessels but not in small microvessels.
      Cosuperfusion of glibenclamide (10 mumol/L) with LNNA produced constriction of
      all sizes of microvessels in response to mastoparan, whereas charybdotoxin (10
      nmol/L) did not affect the mastoparan effect. Pretreatment with glibenclamide
      alone reversed mastoparan dilation to constriction in small microvessels, whereas
      it only offset the dilation without producing constriction in large microvessels.
      We conclude that the activation of GPTX produces homogeneous coronary arterial
      microvascular dilation and that the underlining mechanisms of the dilation are
      vessel size dependent. The L-arginine-nitric oxide pathway mediates the dilation
      only in large microvessels, whereas ATP-sensitive K+ channel activation plays a
      central role in the dilation of small microvessels when GPTX is directly
      activated. ATP-sensitive K+ channels are also involved in the dilation of large
      microvessels in a synergistic fashion with nitric oxide production.

PMID- 8978317
TI  - Expression of inducible nitric oxide synthase in rat experimental autoimmune
      myocarditis with special reference to changes in cardiac hemodynamics.
AB  - Excessive NO produced by an inducible NO synthase (iNOS) has been implicated in
      many types of immune-associated disorders of the cardiovascular system, but it
      remains to be determined whether NO plays a role in myocarditis. Thus, the
      significance of iNOS expression in the development of experimental autoimmune
      myocarditis (EAM), an animal model of human giant cell myocarditis, was
      investigated. Lewis rats were immunized with cardiac myosin and were killed 7,
      14, 21, 28, and 49 days after immunization. The development of severe myocarditis
      was observed on days 14, 21, and 28 in association with significant deterioration
      of hemodynamics determined by cardiac catheterization, which peaked on day 21. In
      parallel with histological severity of myocarditis and deterioration of cardiac
      performance, iNOS activity in the heart measured by [14C]L-citrulline formation
      was markedly increased on days 14, 21, and 28. The expression of iNOS was
      confirmed by immunoblotting and was localized to the infiltrating inflammatory
      cells found in the vicinity of necrotic myocytes by immunohistochemical analysis.
      Aminoguanidine, a selective inhibitor of iNOS, significantly decreased the iNOS
      activity (1.04 +/- 0.37 compared with 29.1 +/- 8.62 pmol.min-1.mg protein-1 in
      untreated myosin-immunized rats, P < .01) and effectively attenuated
      histopathological changes of EAM on day 21. Hemodynamic parameters were also
      improved from 64 +/- 3 to 89 +/- 3 mm Hg for mean blood pressure, from 80 +/- 2
      to 113 +/- 4 mm Hg for left ventricular systolic pressure, from 7.8 +/- 0.3 to
      3.2 +/- 0.3 mm Hg for left ventricular end-diastolic pressure, from 2867 +/- 137
      to 4180 +/- 102 mm Hg/s for +dP/dt, and from 2717 +/- 132 to 4180 +/- 184 mm Hg/s
      for -dP/dt (P < .01). The values after aminoguanidine treatment were not
      significantly different from the control values. These results suggest an
      important role for NO in mediating pathophysiological changes in myocarditis of
      autoimmune origin.

PMID- 8978318
TI  - The effects of hypoxia on pHi in porcine coronary artery endothelium and smooth
      muscle. A novel method for measurements in endothelial cells in situ.
AB  - Endothelium-dependent relaxation of porcine coronary arteries is attenuated under
      hypoxic conditions. Recent evidence also indicates that pHi may modulate the
      release of the endothelium-derived relaxing factor. We tested the hypothesis that
      hypoxia-induced attenuation of endothelium-dependent relaxation is mediated by
      alterations in pHi. We developed a novel method for loading surface cells,
      whereby endothelial cell pHi could be measured in situ on the intact porcine
      coronary artery. Endothelial cells of arterial ring segments were selectively
      loaded with the fluorescent indicator BCECF-AM. Differential loading of the
      endothelial cell layer was verified by confocal microscopy. pHi of the
      endothelial cells in situ and of endothelium-denuded arteries was measured with a
      Photon Technology International spectrofluorimeter. The functional integrity of
      the endothelium was assessed by the endothelium-dependent relaxation to substance
      P in a paired adjacent ring. In the experimental protocol for pHi measurements,
      preparations were perfused with a physiological bicarbonate buffer (pH 7.4),
      stimulated with KCI (29 mmol/L), and then subjected to hypoxia and reoxygenation.
      The mean basal pHi in endothelial cells on the intact six arteries was 6.92 +/-
      0.07. Addition of KCI to the perfusion medium decreased (P = .025) pHi to 6.79 +/
      0.07. Subsequent bubbling with N2 increased (P = .009) pHi to 7.00 +/- 0.06,
      which was reversed by reoxygenation. In contrast to the in situ endothelium, pHi
      of the smooth muscle was not significantly altered from its basal value of 7.24
      +/- 0.06 (n = 5) by either KCI or hypoxia. This differential behavior
      corroborated the confocal data indicating differential dye loading. These data
      thus suggest that oxygen-sensitive alterations in pHi may be an important
      mechanism of signal transduction in endothelial cells.

PMID- 8978319
TI  - Mechanical strain tightly controls fibroblast growth factor-2 release from
      cultured human vascular smooth muscle cells.
AB  - Although fibroblast growth factor-2 (FGF-2) participates in the response to
      vascular injury, the role of cellular deformation in FGF-2 release is
      incompletely understood. To test the hypothesis that mechanical strain tightly
      controls FGF-2 release, a novel device was used to impose homogeneous and uniform
      biaxial strain to human vascular smooth muscle cells. Release of FGF-2 increased
      with the number of cycles of strain (14%, 1 Hz); 1, 9, and 90 cycles of strain,
      respectively, released 0.55 +/- 0.06%, 2.9 +/- 0.3%, and 5.5 +/- 1.3% of the
      total cellular FGF-2 (versus 0.00 +/- 0.40% for control, P < .05), but release
      was not further increased for strain of 90 to 90,000 cycles. Mechanical release
      of FGF-2 depended on both the frequency and amplitude of deformation. For
      example, strain (90 cycles, 1 Hz) at 4% amplitude released only 0.1 +/- 0.1% of
      the total FGF-2, but strain at 14% and 33% amplitudes, respectively, released 5.7
      +/- 0.5% and 19.0 +/- 3.0% of the FGF-2 cellular pool (P < .05), suggesting a
      strain amplitude threshold for FGF-2 release. Injury to a subpopulation of cells
      increased with the frequency and amplitude of strain, but cells were not injured
      by strains below 10% amplitude. Strain following pretreatment with heparin
      released 12.6 +/- 1.6% of the total FGF-2 (versus 15.8 +/- 0.9% for strain alone,
      P < .05), indicating that most FGF-2 was liberated from the nuclear or
      cytoplasmic pools and not from low-affinity extracellular receptors. Conversely,
      strain in the presence of heparin released 25.2 +/- 3.5% of the total FGF-2
      (versus 15.6 +/- 2.6% for strain alone, P < .05). Thus, cellular strain closely
      modulates the release of intracellular FGF-2 from human vascular smooth muscle
      cells, but FGF-2 release is negligible in response to the smaller strains that
      occur in the normal artery. In addition, larger mechanical strains lead to
      transfer of intracellular FGF-2 to the extracellular low-affinity receptors,
      where FGF-2 may be displaced by heparin. These observations provide insight into
      the mechanisms by which deforming vascular injury, such as that produced by
      arterial interventions, may elicit a proliferative response.

PMID- 8978320
TI  - Exogenous oxidized low-density lipoprotein injures and alters the barrier
      function of endothelium in rats in vivo.
AB  - Oxidation converts low-density lipoprotein (LDL) into a cytotoxin in vitro.
      Oxidized LDL exists in vivo in atherosclerotic lesions and possibly in plasma.
      Many cell functions are altered in vitro by oxidized LDL, but few have been
      examined in vivo. To test whether oxidized LDL could injure endothelial cells and
      alter endothelial permeability to macromolecules in vivo, we infused oxidized
      LDL, native LDL, or their solvent intravenously into rats. Subsequently,
      endothelial cell injury and proliferation were measured, and the transport into
      the aorta wall of the macromolecule horseradish peroxidase (HRP) was quantified.
      Transport data were analyzed using mathematical models of macromolecular
      transport; parameters were estimated by optimally fitting model-predicted HRP
      concentrations to experimental data. Compared with native LDL or solvent control
      infusion, oxidized LDL infusion increased (1) the number of injured aortic
      endothelial cells fivefold to sixfold at 36 hours, (2) proliferation of
      endothelial cells at 48 hours, (3) intimal and medial accumulations of HRP
      twofold to threefold at 48 hours, and (4) the permeability coefficient of the
      endothelium to HRP fourfold to fivefold at 48 hours. Hence, oxidized LDL
      administered in vivo can injure the endothelium, despite the presence of
      endogenous antioxidants, compromising the function of the endothelium as a
      permeability barrier.

PMID- 8978321
TI  - p22phox mRNA expression and NADPH oxidase activity are increased in aortas from
      hypertensive rats.
AB  - Recent studies suggest that superoxide production by the NADPH/NADH oxidase may
      be involved in smooth muscle cell growth and the pathogenesis of hypertension. We
      previously showed that angiotensin II (Ang II) activates a p22phoxbased
      NADPH/NADH oxidase in cultured rat vascular smooth muscle cells and in animals
      made hypertensive by infusion of Ang II. To investigate the mechanism responsible
      for this increased oxidase activity, we examined p22phox mRNA expression in rats
      made hypertensive by implanting an osmotic minipump that delivered Ang II (0.7
      mg/kg per day). Blood pressure began to increase 3 days after the start of Ang II
      infusion and remained elevated for up to 14 days. Expression of p22phox mRNA in
      aorta was also increased after 3 days and reached a maximum increase of 338 +/-
      41% by 5 days after pump implantation compared with the value after sham
      operation. This increase in mRNA expression was accompanied by an increase in the
      content of the corresponding cytochrome (twofold) and NADPH oxidase activity (179
      +/- 11% of that in sham-operated rats 5 days after pump implantation). Treatment
      with the antihypertensive agents losartan (25 mg/kg per day) or hydralazine (15
      mg/kg per day) inhibited this upregulation of mRNA levels and activity.
      Furthermore, infusion of recombinant heparin-binding superoxide dismutase
      decreased both blood pressure and p22phox mRNA expression. In situ hybridization
      of aortic tissue showed that p22phox mRNA was expressed in medial smooth muscle
      as well as in the adventitia. These findings suggest that Ang II-induced
      hypertension activates the NADPH/NADH oxidase system by upregulating mRNA levels
      of one or several components of this oxidase system, including the p22phox, and
      that the NADPH/NADH oxidase system is associated with the pathology of
      hypertension in vivo.

PMID- 8978322
TI  - Involvement of phosphorylation in doxorubicin-mediated myofibril degeneration. An
      immunofluorescence microscopy analysis.
AB  - Loss of myofilaments has been observed in both adaptive cardiac responses (i.e.,
      hypertrophy) as well as in chemotheraputic use of antineoplastic drugs with
      cardiotoxic side effects (i.e., doxorubicin). An understanding of the
      degenerative process is a prerequisite for determining approaches to limit the
      cardiomyopathic changes associated with chronic heart disease or long-term
      chemotheraputic treatments. However, little is known about the specific events
      and molecular changes that initiate the degenerative process. To study this
      process, neonatal rat cardiomyocytes were treated with doxorubicin, which induced
      rapid and widespread thin-filament degeneration as observed by fluorescence
      confocal microscopy. Which demonstrated deterioration of sarcomeric thin-filament
      structure. Changes in the spontaneous beating of cardiomyocytes corresponding
      with myofibrillar degeneration were apparent using differential interference
      contrast video microscopy. After finding induction of kinase activity by
      doxorubicin in cultured cardiomyocytes, the protective effects of specific
      inhibitors of kinase activity were assessed for their ability to inhibit
      doxorubicin-induced myofibrillar break-down. Doxorubicin-induced changes appeared
      similar to the degeneration observed after treatment with a protein kinase
      activator (phorbol 12-myristate 13-acetate) or a serine-threonine protein
      phosphatase inhibitor (okadaic acid). Collectively, these results indicate that
      activation of protein kinase is an important event in the initiation of
      myofibrillar degeneration by doxorubicin. Further analyses of myofibrillar
      proteins with respect to biochemical modifications will be necessary to determine
      if phosphorylation events transmit signal(s) to initiate degeneration.

PMID- 8978323
TI  - Modulation of renal cortical blood flow during static exercise in humans.
AB  - During static exercise, several reflex systems that increase sympathetic nerve
      activity, heart rate, arterial pressure, and cardiac output are activated. At
      rest, the renal circulation receives the most blood flow per tissue weight of any
      organ in the body. However, the renal circulatory response to static exercise has
      not been studied in humans because of technical limitations in methods for
      measuring rapid changes in renal blood flow. The aim of this study was to
      determine the renal blood flow response to static exercise in healthy humans and,
      specifically, to clarify the reflex mechanisms underlying this response. Renal
      cortical blood flow was measured using dynamic positron emission tomography and
      the blood flow agent oxygen-15 water. Graded handgrip exercise, posthandgrip
      circulatory arrest, and administration of intra-arterial adenosine were performed
      to clarify the mechanisms controlling renal blood flow during static exercise.
      The major new findings in this study are that in healthy humans (1) renal
      cortical blood flow decreases (basal versus handgrip, 4.4 +/- 0.1 versus 3.5 +/-
      0.1 mL.min-1.g-1; P = .008) and renal cortical vascular resistance increases
      (basal versus handgrip, 17 +/- 1 versus 26 +/- 2 U; P = .01) in response to
      static handgrip exercise; (2) central command and/or the mechanoreflex
      contributes importantly to the early decrease in renal blood flow (basal versus
      handgrip, 4.2 +/- 0.2 versus 3.5 +/- 0.3 mL.min-1.g-1; P = .04) and to the
      increase in renal cortical vascular resistance (basal versus handgrip, 20 +/- 1
      versus 25 +/- 2 U; P = .04); (3) the muscle metaboreflex contributes to further
      decreases in renal blood flow (basal versus posthandgrip circulatory arrest, 4.3
      +/- 0.1 versus 3.5 +/- 0.2 mL.min-1.g-1; P = .002) and increases in renal
      cortical vascular resistance (basal versus handgrip, 18 +/- 1 versus 25 +/- 3 U;
      P = .002); and (4) exogenous adenosine activates the muscle metaboreflex
      producing reflex renal vasoconstriction and decreased renal blood flow, which may
      implicate endogenous adenosine generated during ischemic exercise as a potential
      activator of the muscle metaboreflex during ischemic handgrip exercise.

PMID- 8978324
TI  - Simulated ischemia increases the susceptibility of rat cardiomyocytes to
      hypercontracture.
AB  - The hypothesis that rat cardiomyocytes become susceptible to hypercontracture
      after anoxia/reoxygenation was investigated. The cells were gradually overloaded
      with Ca2+ after different periods of simulated ischemia (substrate-free anoxia,
      medium at pH 6.4) followed by 20 minutes of reoxygenation. The cytosolic Ca2+
      concentration (measured with fura 2) at which the cells developed maximal
      hypercontracture (Camax) was used as an index for their susceptibility to
      hypercontracture (SH). SH was increased in cardiomyocytes after prolonged periods
      of simulated ischemia; ie, these cells developed hypercontracture at
      significantly lower cytosolic Ca2+ levels than did normoxic cells (Camax, 0.80 +/
      0.05 mumol/L versus 1.27 +/- 0.05 mumol/L; P < .01). To find the possible cause
      of increased SH, the influence of Ca2+ overload, acidosis, and protein
      dephosphorylation were studied. Prevention of cytosolic Ca2+ overload in anoxic
      cardiomyocytes or imitation of ischemic acidosis in normoxic cells did not
      influence Camax. In contrast, use of 10 mumol/L cantharidin (inhibitor of protein
      phosphatases 1 and 2A) during anoxic superfusion prevented the reduction of
      Camax. Furthermore, treatment of normoxic cardiomyocytes with 20 mmol/L of the
      chemical phosphatase 2,3-butanedione monoxime reduced Camax. Therefore, prolonged
      simulated ischemia increases susceptibility of cardio-myocytes to
      hypercontracture. This seems to be due to protein dephosphorylation.

PMID- 8978325
TI  - Hydroxyl radical inhibits sarcoplasmic reticulum Ca(2+)-ATPase function by direct
      attack on the ATP binding site.
AB  - Oxygen-derived free radicals have been reported to damage the sarcoplasmic
      reticulum (SR) Ca(2+)-ATPase, potentially contributing to cellular Ca2+ overload
      and myocardial damage after ischemia and reperfusion. To determine whether the
      ATP binding site on Ca(2+)-ATPase is involved in oxygen radical injury, SR
      vesicles containing bound Ca(2+)-ATPase were isolated from rabbit cardiac and
      skeletal muscle and exposed to a hydroxyl radical (.OH)-generating system
      consisting of H2O2 and Fe(3+)-nitrilotriacetic acid in amounts that generate a
      magnitude of .OH similar to that which occurs in the reperfused heart. .OH
      exposure completely inhibited Ca(2+)-ATPase activity and SR 45Ca uptake for both
      cardiac and skeletal muscle. In contrast, when the purified vesicles were
      premixed with 1 mmol/L ATP before exposure to .OH, complete protection was
      observed: there was no loss of ATPase activity or 45Ca transport. No significant
      protection occurred with adenosine, sucrose, AMP, or ADP (1 mmol/L each). SDS-gel
      electrophoresis indicated that .OH did not damage the primary structure of the
      enzyme. Electron paramagnetic resonance spin-trapping experiments demonstrated
      that ATP did not scavenge .OH. These results suggest that .OH denatures the SR
      Ca(2+)-ATPase by directly attacking the ATP binding site, and occupation of the
      active site by ATP protects against .OH-induced loss of enzymatic activity and SR
      Ca2+ transport. The depletion of ATP that occurs during ischemia may enhance the
      toxic effect of .OH at the time of reperfusion.

PMID- 8978326
TI  - Intracellular Ca2+ increases the mitochondrial NADH concentration during elevated
      work in intact cardiac muscle.
AB  - It is not clear how mitochondrial energy production is regulated in intact tissue
      when energy consumption suddenly changes. Whereas mitochondrial [NADH] ([NADH]m)
      may regulate cellular respiration rate and energetic state, it is not clear how
      [NADH]m itself is controlled during increased work in vivo. We have varied work
      and [Ca2+] in intact cardiac muscle while assessing [NADH]m using fluorescence
      spectroscopy. When increased work was accompanied by increasing average [Ca2+]c
      (by increasing [Ca2+]c or pacing frequency), [NADH]m initially fell and
      subsequently recovered to a new steady state level. Upon reduction of work,
      [NADH]m overshot and then returned to control levels. In contrast, when work was
      increased without increasing average [Ca2+]o (by increasing sarcomere length),
      [NADH]m fell similarly, but no recovery or overshoot was observed. This Ca(2+)
      dependent recovery and overshoot may be attributed to Ca(2+)-dependent
      stimulation of mitochondrial dehydrogenases. We conclude that the immediate
      initial increase in respiration rate upon elevation of work is not activated by
      increased [NADH]m (since [NADH]m rapidly fell) or by [Ca2+]o (since work could
      also be increased at constant [Ca2+]c). However, during sustained high work, a
      Ca(2+)-dependent mechanism causes slow recovery of [NADH]m toward control values.
      This demonstrates a Ca(2+)-dependent feed-forward control mechanism of cellular
      energetics in cardiac muscle during increased work.

PMID- 8978327
TI  - Dissociated spatial patterning of gap junctions and cell adhesion junctions
      during postnatal differentiation of ventricular myocardium.
AB  - Nonuniformity in the spatial patterning of gap junctions between heart muscle
      cells is now recognized as an important determinant of electromechanical function
      in working myocardium. Breakdown of the normal geometry of electrical
      intercellular connectivity in diseased myocardium correlates with reentry,
      arrhythmia, and conduction disturbance. The developmental mechanism(s) that
      determines this precise spatial order in gap junction organization in normal
      myocardium is at present unknown. To examine this question, we have used
      immunoelectron and immunoconfocal microscopy to analyze the spatial distributions
      of gap junctional (connexin43), desmosomal (desmoplakin), and adherens junctional
      (N-cadherin) components during maturation of rodent and canine left ventricular
      myocardium. In rats, a striking divergence in the distribution of gap junctions
      and cell adhesion junctions emerged within the first 20 days of postnatal life.
      It was found that although gap junctions initially demonstrated dispersed
      distributions across myocyte cell membranes, desmosomes and adherens junctions
      showed more rapid polarization toward cell termini (ie, nascent intercalated
      disks) after birth. Over subsequent postnatal development (20 to 90 postnatal
      days), gap junctions became progressively concentrated in these cell adhesion
      junction-rich zones of membrane. Quantitative analyses of this process in a
      series of rats aged 15 embryonic and 1, 5, 10, 20, 40, 70, and 90 postnatal days
      indicated that significantly higher levels (P < .01) of N-cadherin and
      desmoplakin than of connexin43 were immunolocalized to cell termini by as early
      as postnatal day 5. Although all three junctions types showed increasing
      polarization to myocyte termini with development, variation between junctions
      remained significant (P < .05) at all times points between 5 and 70 postnatal
      days. Only at 90 postnatal days, when the animals were nearly full grown, did the
      proportions of gap junction, desmosome, and adherens junction at intercalated
      disks become statistically similar (P > .05). Examination of myocardium from 1-
      and 3-month-old canines revealed that related differential changes to the
      spatiotemporal distribution of intercellular junctions occurred during postnatal
      maturation of the dog heart, suggesting that the process was not rodent specific.
      It is concluded that this progressive change in the organization and pattern of
      association between gap junctions and cell adhesion junctions is likely to be an
      important factor in maturation of electromechanical function within the mammalian
      heart.

PMID- 8978328
TI  - Na(+)-H+ exchange inhibition protects against mechanical, ultrastructural, and
      biochemical impairment induced by low concentrations of lysophosphatidylcholine
      in isolated rat hearts.
AB  - Lysophophatidylcholine (LysoPC) accumulates rapidly in the ischemic myocardium
      and is an important mediator of ischemia-induced cell injury. Na(+)-H+ exchange
      (NHE) inhibition has been demonstrated to protect the ischemic and reperfused
      myocardium. We determined whether NHE inhibition can also modulate cardiotoxicity
      produced by LysoPC (3 and 5 mumol/L) in isolated rat hearts. At 3 mumol/L, LysoPC
      produced a depression in left ventricular developed pressure (LVDP) and elevation
      in left ventricular end-diastolic pressure (LVEDP), which were 19 +/- 7% and 1290
      +/- 205% of pre-LysoPC values, respectively, after 30 minutes of treatment. In
      the presence of the NHE inhibitor 4-isopropyl-3-methylsulfonylbenzoyl-guanidine
      methanesulfonate (HOE 642, 5 mumol/L), LVDP was reduced to only 80.8 +/- 8.6%,
      and LVEDP increased to 270 +/- 32% (P < .05 for both parameters). LysoPC
      significantly depressed tissue ATP, creatine phosphate, and glycogen contents and
      increased lactate levels, all of which were significantly attenuated by HOE 642.
      Moreover, marked LysoPC-induced ultrastructural abnormalities, including
      mitochondrial and myofibrillar disruption, were totally prevented by HOE 642.
      This protection was mimicked by another NHE inhibitor, methylisobutylamiloride (5
      mumol/L). HOE 642 was also effective against injury produced by 5 mumol/L LysoPC
      although, generally, the protection was less marked than that observed against 3
      mumol/L; LVDP depression after 30 minutes was 10.1 +/- 4.3% and 41.4 +/- 10.4% of
      pre-LysoPC values in control and HOE 642-treated hearts, respectively (P < .05),
      whereas corresponding LVEDP elevations were 1629 +/- 393% and 990 +/- 144% (P >
      .05). In myocytes superfused with bicarbonate-free buffer subjected to acid
      loading by NH4Cl pulsing, pH recovery (as measured by acid flux) was
      significantly stimulated by 3 mumol/L LysoPC, indicative of NHE activation. Our
      study shows that cardiac injury produced by low concentrations of LysoPC can be
      effectively attenuated by NHE inhibition. The results also suggest that the
      beneficial effects of NHE inhibitors on the ischemic myocardium may be, at least
      partially, mediated by inhibiting the deleterious effects of LysoPC.

PMID- 8978329
TI  - Evidence that outwardly rectifying Cl- channels underlie volume-regulated Cl-
      currents in heart.
AB  - Swelling-induced Cl- current (ICl.swell) is present in most cardiac tissues, but
      the unitary channel underlying ICls.well is unknown. We used the cell-attached
      patch-clamp technique to assess the properties of single channels underlying
      ICls.well and the basally active Cl- current (ICl.b) in rabbit atrial myocytes.
      Under isotonic conditions, single outwardly rectifying Cl- channels (ORCCs) with
      a slope conductance of 28 +/- 1 pS at the reversal potential were observed in 21
      (5.7%) of 367 patches. Unconditional kinetic analysis revealed at least three
      open and four closed-channel states. Hypotonic superfusion-induced swelling
      resulted in the appearance of active channels in 41 (15.5%) of 265 patches
      without channel activity under isotonic conditions and caused a second active
      channel to appear in 3 of 14 patches showing a single channel under isotonic
      conditions. Overall, channels were seen in 54 of 336 patches under hypotonic
      conditions (16.1%, P < .001 versus isotonic conditions). The current-voltage
      relations, reversal potential-[Cl-]o relations, open probability, and kinetics of
      swelling-induced channels were indistinguishable from those of ORCCs under
      isotonic conditions. Unitary ORCCs, ICl.b, and ICl.swell were strongly and
      similarly inhibited by tamoxifen. Swelling-induced increases in macroscopic Cl-
      current were attributable to an increase in the number of active ORCCs with no
      significant effects on single-channel amplitude or open probability. Estimated
      macroscopic currents based on cell surface area, patch dimensions, single-channel
      ORCC current amplitude, open probability, and density were consistent with
      measured values of ICl.b and ICl.swell. We conclude that ORCCs underlie volume
      regulated basal and swelling-induced Cl- currents in isolated rabbit atrial
      myocytes.

PMID- 8978330
TI  - Combined inhibition of endothelin and angiotensin II receptors blocks volume load
      induced cardiac hormone release.
AB  - Volume expansion has been shown to increase plasma atrial natriuretic peptide
      (ANP) levels, but the precise role of paracrine and autocrine factors in stretch
      induced cardiac hormone release is not clear. In the present study, we report the
      effects of endothelin (ET) and angiotensin receptor (AT receptor) antagonists on
      baseline and atrial stretch-induced immunoreactive ANP (IR-ANP) and
      immunoreactive N-terminal ANP (IR-NT-ANP) release in vivo by using BQ-123 (ETA
      receptor antagonist), bosentan (ETA and ETB receptor antagonist), and losartan
      (AT1 receptor antagonist). Intravenous administration of BQ-123 had no
      significant effect on baseline hemodynamics in conscious rats, whereas bosentan
      (10 mg/kg) and losartan (10 mg/kg) decreased slightly (4 to 7 mm Hg, P < .05 to
      .001) the mean arterial pressure. Both the ETA receptor antagonist BQ-123 and
      ETA/ETB receptor antagonist bosentan decreased plasma ANP and NT-ANP responses to
      volume load (P < .05 to .001), whereas the AT1 receptor antagonist losartan had
      no significant effect on this response. The relative increase in plasma IR-ANP
      corresponding to a 3 mm Hg increase in right atrial pressure was 2.7-fold in the
      vehicle-treated group. BQ-123 (0.3 and 1.0 mg/kg) decreased this response 2.5-
      and 2.1-fold (P < .05); bosentan (3 and 10 mg/kg), 1.7-fold (P < .001) and 1.9
      fold (P < .05); and bosentan (10 mg/kg)+losartan (10 mg/kg), 1.6-fold (P < .001).
      The responses in plasma IR-NT-ANP decreased simultaneously. These results
      indicate that combined inhibition of ETA/B and AT1 receptors almost completely
      blocks ANP response to acute volume load. Therefore, our study shows that
      endogenous paracrine and/or autocrine factors liberated in response to atrial
      wall stretch rather than myocyte stretch itself are responsible for the
      activation of ANP peptide secretion in response to acute volume load. Our results
      also show that ETA receptors are more important in the regulation of mechanical
      stretch-induced changes in cardiac hormone secretion than AT1 receptors.

PMID- 8978331
TI  - Electrophysiologic effects of acute myocardial ischemia. A mechanistic
      investigation of action potential conduction and conduction failure.
AB  - A multicellular ventricular fiber model was used to determine mechanisms of
      slowed conduction and conduction failure during acute ischemia. We simulated the
      three major pathophysiological component conditions of acute ischemia: elevated
      [K+]o, acidosis, and anoxia. Elevated [K+]o was the major determinant of
      conduction, causing supernormal conduction, depressed conduction, and conduction
      block as [K+]o was gradually increased from 4.5 to 14.4 mmol/L. Only elevated
      [K+]o caused conduction failure when varied within the range reported for acute
      ischemia. Before block, depressed upstrokes consisted of two distinct components:
      the first to the fast Na+ current (INa) and the second to the L-type Ca2+ current
      (ICa(L)). Even in highly depressed conduction, excitability was maintained by
      INa, with conduction block occurring at 95% INa inactivation. However, because
      ICa(L) supported the later phase of the depressed upstroke, ICa(L) enhanced
      conduction and delayed block by increasing the electrotonic source current. At
      [K+]o = 18 mmol/L, slow action potentials generated by ICa(L) were obtained with
      10% ICa(L) augmentation. However, in the presence of acidosis and anoxia,
      significantly larger (120%) ICa(L) augmentation was required. The depressant
      effect was due mostly to anoxic activation of outward ATP-sensitive K+ current,
      which counteracts inward ICa(L) and, by lowering the action potential amplitude,
      decreases the electrotonic current available to depolarize downstream cells. The
      simulations highlight the interactive nature of electrophysiological ischemic
      changes during propagation and demonstrate that both membrane changes and load
      factors (by downstream fiber) must be considered.

PMID- 8978332
TI  - Angiotensin II stimulates c-Jun NH2-terminal kinase in cultured cardiac myocytes
      of neonatal rats.
AB  - Many lines of evidence have suggested that angiotensin II (Ang II)plays an
      important role in cardiac hypertrophy. Ang II not only increases protein
      synthesis but also induces the reprogramming of gene expression in cultured
      cardiac myocytes. In the present study, to elucidate the mechanism by which Ang
      II regulates gene expression in cardiac myocytes, we examined whether Ang II
      activates c-Jun NH2-terminal kinase (JNK), which is a member of the mitogen
      activated protein kinase family and activates the transcription factor, activator
      protein-1 (AP-1). The activity of JNK increased 5 minutes after the addition of
      Ang II, peaked at 20 minutes, and gradually decreased thereafter. Examination of
      the Ang II dose-response relation revealed detectable JNK activation at 10(-9)
      mol/L and maximal activation at 10(-6) mol/L. Ang II activated JNK through the
      AT1 receptor, and the activation was attenuated by the downregulation of protein
      kinase C or the chelation of intracellular Ca2+. Although the addition of either
      Ca2+ ionophore or phorbol ester resulted in little or no activation of JNK,
      simultaneous addition of both Ca2+ ionophore and phorbol ester markedly activated
      JNK. Slight expressions of the c-jun gene were observed in unstimulated cardiac
      myocytes, and Ang II increased expressions of the c-jun gene as well as the c-fos
      gene. Ang II increased transcription of the endothelin-1 gene through the AP-1
      binding site. In conclusion, Ang II may activate JNK in cultured cardiac myocytes
      through an increase in intracellular Ca2+ and activation of protein kinase C, and
      the activated JNK may regulate gene expression by activating AP-1 during Ang II
      induced cardiac hypertrophy.

PMID- 8978333
TI  - XII International Congress of Eye Research. Yokohama, Japan, September 29-October
      4, 1996. Abstracts.

PMID- 8978334
TI  - Epilepsy.
AB  - Diagnosis and management of the epilepsies are routinely performed by primary
      care physicians. In the United States, only 17% of patients with new-onset
      epilepsy are examined by neurologic specialists, and even fewer patients employ
      neurologists for their ongoing care. With the changes dictated by the evolving
      health care system in the United States, the responsibilities for the treatment
      of patients with epilepsies by primary care physicians will continue to increase.
      At the same time, there has been an explosion of new information about the
      diagnosis, evaluation, natural history, and neurobiologic aspects of epilepsy.
      New medical and surgical treatments are being introduced with a quickening pace.
      Finally, the concept that certain epilepsies may be progressive and that early
      identification and aggressive treatment represent one's best chance for
      establishing control for these patients has gained widespread confirmation from
      both clinical and animal model studies. The past standard of care is quickly
      ending. No longer should a patient or a physician accept only partial seizure
      control. This monograph attempts to lay the basis for improved understanding of
      epilepsy so that our patients will be seizure free without side effects and will
      be able to fully participate in our society.

PMID- 8978335
TI  - Image of the month. Sunflower cataract.

PMID- 8978336
TI  - Multiple lymphomatous polyposis of the gastrointestinal tract: prospective
      clinicopathologic study of 31 cases. Groupe D'etude des Lymphomes Digestifs.
AB  - BACKGROUND & AIMS: Multiple lymphomatous polyposis (MLP) is an uncommon type of
      gastrointestinal lymphoma. The aim of this study was to analyze the
      clinicopathologic features and outcome of a large series of patients. METHODS:
      From 1984 to 1995, 31 patients were enrolled prospectively. Exhaustive staging
      and immunohistochemical analysis were performed. The first 10 patients were
      treated with cyclophosphamide-vincristine-prednisolone (COP) and the subsequent
      21 with doxorubicin-teniposide-cyclophosphamide-prednisolone (AVmCP). Eleven
      patients were treated with high-dose radiochemotherapy and stem cell
      autotransplantation because of partial response or relapse. RESULTS: Advanced age
      and multiple polyps involving several gastrointestinal segments characterized
      initial clinical presentation. The typical tumor cell phenotype (pan-B+, CD5+,
      and CD10-) along with Bcl-1 rearrangement indicated that MLP is the
      gastrointestinal counterpart of mantle cell lymphoma. After COP treatment, only 3
      patients achieved partial remissions, whereas 80% of patients after AVmCP
      treatment achieved complete or good partial remission. High-dose
      radiochemotherapy changed partial into complete remission in 80% of cases. None
      of the initial 10 patients survived for 3 years, but the expected 5-year survival
      rate was 59% in patients receiving the anthracycline-containing regimen (P <
      0.0001). CONCLUSIONS: MLP is a distinct entity among gastrointestinal lymphomas.
      An anthracycline-containing multidrug regimen and high-dose radiochemotherapy
      supported by autotransplantation seem to improve its poor prognosis.

PMID- 8978337
TI  - Relative sensitivity of colonoscopy and barium enema for detection of colorectal
      cancer in clinical practice.
AB  - BACKGROUND & AIMS: The relative sensitivities of barium enema and colonoscopy for
      colorectal cancer are still debated. The aim of this study was to determine the
      relative sensitivity of barium enema and colonoscopy in general clinical
      practice. METHODS: Medical records of 2193 consecutive colorectal cancer cases
      identified in 20 central Indiana hospitals were reviewed. All procedures
      performed within 3 years of the diagnosis were identified. RESULTS: The
      sensitivity of colonoscopy for colorectal cancer (95%) was greater than that for
      barium enema (82.9%), with an odds ratio of 3.93 for a missed cancer by barium
      enema compared with colonoscopy. The sensitivity of double-contrast barium enema
      (85.2%) was not different from that of single-contrast (81.8%). Barium enema
      performed no better in the right than the left colon. Cancers detected by
      colonoscopy were more likely to be Dukes' class A (24.9%) than cancers detected
      by barium enema (9.8%). Colonoscopy performed by gastroenterologists was more
      sensitive (97.3%) for cancer than colonoscopy by nongastroenterologists (87%),
      with an odds ratio of 5.36 for a missed cancer by a nongastroenterologist
      compared with a gastroenterologist. CONCLUSIONS: Hospital quality assurance
      committees and/or third-party payors should review the sensitivity of barium
      enema and colonoscopy by practitioners in their institutions. Corrective measures
      are recommended when sensitivity deviates significantly below the standard set by
      gastroenterologists performing colonoscopy in this study.

PMID- 8978338
TI  - Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies.
AB  - BACKGROUND & AIMS: The miss rate of colonoscopy for neoplasms is poorly
      understood. The aim of this study was to determine the miss rate of colonoscopy
      by same day back-to-back colonoscopy. METHODS: Two consecutive same day
      colonoscopies were performed in 183 patients. The patients were randomized to
      undergo the second colonoscopy by the same or a different endoscopist and in the
      same or different position. RESULTS: The overall miss rate for adenomas was 24%,
      27% for adenomas < or = 5 mm, 13% for adenomas 6-9 mm, and 6% for adenomas > or =
      1 cm. Patients with two or more adenomas at the first examination were more
      likely than patients with no or one adenoma detected at the first examination to
      have one or more adenomas at the second examination (odds ratio, 3.3; 95%
      confidence interval, 1.69-6.46). Right colon adenomas were missed more often
      (27%) than left colon adenomas (21%), but the difference was not significant.
      There was evidence of variation in sensitivity between endoscopists, but
      significant miss rates for small adenomas were found among essentially all
      endoscopists. CONCLUSIONS: Using current colonoscopic technology, there are
      significant miss rates for adenomas < 1 cm even with meticulous colonoscopy. Miss
      rates are low for adenomas > or = 1 cm. The results suggest the need for
      improvements in colonoscopic technology.

PMID- 8978339
TI  - The effect of folic acid supplementation on the risk for cancer or dysplasia in
      ulcerative colitis.
AB  - BACKGROUND & AIMS: Two case-control studies have shown that folate may protect
      against neoplasia in ulcerative colitis. This historical cohort study was
      performed to better define this association. METHODS: The records of 98 patients
      with ulcerative colitis who had disease proximal to the splenic flexure for at
      least 8 years were reviewed. Documented folate use of at least 6 months was
      deemed a positive exposure. RESULTS: Of the patients, 29.6% developed neoplasia
      and 40.2% took folate supplements. The adjusted relative risk (RR) of neoplasia
      for patients taking folate was 0.72 (95% confidence interval [CI], 0.28-1.83).
      The dose of folate varied with the risk of neoplasia (RR, 0.54 for 1.0 mg folate;
      RR, 0.76 for 0.4 mg folate in a multivitamin compared with patients taking no
      folate). Folate use also varied with the degree of dysplasia (RR for cancer,
      0.45; RR for high-grade dysplasia, 0.52; RR for low-grade dysplasia, 0.75
      compared with patients with no dysplasia) (P = 0.08). CONCLUSIONS: Although not
      statistically significant, the RR for folate supplementation on the risk of
      neoplasia is < 1 and shows a dose-response effect, consistent with previous
      studies. Daily folate supplementation may protect against the development of
      neoplasia in ulcerative colitis.

PMID- 8978340
TI  - Transforming growth factor beta type II receptor gene mutations in adenomas from
      hereditary nonpolyposis colorectal cancer.
AB  - BACKGROUND & AIMS: Germline mutations of DNA mismatch repair genes are
      responsible for cancer susceptibility in hereditary nonpolyposis colorectal
      cancer (HNPCC) kindreds. Transforming growth factor beta type II receptor (TGF
      beta RII) has been found to be somatically altered in HNPCC. The aim of this
      study was to clarify further the role of TGF-beta RII alterations in HNPCC
      tumorigenesis, particularly in adenomas. METHODS: Fourteen adenoma specimens and
      13 cancer specimens from 10 patients with HNPCC were screened for mutations in
      the short repeated sequences of the TGF-beta RII gene by polymerase chain
      reaction-single-strand conformation polymorphism. Mismatch repair genes,
      replication errors, and c-K-ras 2 were also analyzed in HNPCC tumors. RESULTS:
      Alterations of the TGF-beta RII gene at the short poly(A) repeat were found in 8
      (57%) adenoma specimens and 11 (85%) cancer specimens. They were found at an
      earlier stage of adenomas. Two adenoma specimens showed two-hit inactivation of
      mismatch repair genes. Replication errors were detectable in 13 (93%) adenoma
      specimens. Mutations in c-K-ras 2 codon 12 were detected at a 50% frequency in
      adenoma specimens. CONCLUSIONS: These data indicate a strong association between
      TGF-beta RII gene alterations and adenoma-carcinoma progression in HNPCC.

PMID- 8978341
TI  - A transforming growth factor beta 1 receptor type II mutation in ulcerative
      colitis-associated neoplasms.
AB  - BACKGROUND & AIMS: Numerous gastrointestinal tumors, notably sporadic and
      ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias, gastric
      cancers, and esophageal carcinomas, manifest microsatellite instability.
      Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII)
      mutation in a coding microsatellite was described in colorectal carcinomas
      showing instability. One hundred thirty-eight human neoplasms (61 UC-associated,
      35 gastric, 26 esophageal, and 16 sporadic colorectal) were evaluated for this
      TGF-beta 1RII mutation. METHODS: Whether instability was present at other
      chromosomal loci in these lesions was determined. In lesions manifesting or
      lacking instability, the TGF-beta 1RII coding region polydeoxyadenine (poly A)
      microsatellite tract was polymerase chain reaction amplified with 32P-labeled
      deoxycytidine triphosphate. Polymerase chain reaction products were
      electrophoresed on denaturing gels and exposed to radiographic film. RESULTS:
      Three of 18 UC specimens with instability at other chromosomal loci (17%) showed
      TGF-beta 1RII poly A tract mutation, including 2 cancers and 1 dysplasia;
      moreover, 2% of UC specimens without instability (1 of 43) (1 cancer), 81% of
      unstable sporadic colorectal cancers (13 of 16), and none of the 61 stable or
      unstable gastric or esophageal cancers contained TGF-beta 1RII mutations.
      CONCLUSIONS: Mutational inactivation of the poly A microsatellite tract within
      TGF-beta 1RII occurs early and in a subset of unstable UC neoplasms and commonly
      in sporadic colorectal cancers but may be rare in unstable gastric and esophageal
      tumors.

PMID- 8978342
TI  - Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma:
      relationship with patient survival.
AB  - BACKGROUND & AIMS: The E-cadherin-catenin complex plays a critical role in the
      maintenance of normal tissue architecture. Mutation of any of its components is
      believed to result in loss of cell-cell adhesion and contribute to neoplasia. The
      aim of this study was to examine the expression of E-cadherin and alpha-, beta-,
      and gamma-catenin in gastric carcinoma and dysplasia and determine any
      relationship with tumor characteristics and survival. METHODS: Immunoperoxidase
      staining of E-cadherin and alpha-, beta-, and gamma-catenin was performed using
      89 gastric carcinomas, lymph node metastases, and gastric biopsy specimens from
      14 patients with dysplasia and 10 healthy controls. RESULTS: Membranous staining
      was observed in control biopsy specimens for all components of the complex. Up to
      57% of gastric dysplasia and 90% of tumors stained abnormally for one or more
      components of the cadherin-catenin complex. Abnormal E-cadherin and gamma-catenin
      staining occurred more frequently in diffuse than intestinal tumors (P < 0.0005
      and < 0.05, respectively). No association with tumor grade or stage was found. A
      survival advantage was noted in intestinal and diffuse tumors retaining
      membranous expression of beta-catenin, independent of tumor type, grade, or stage
      (P < 0.005). CONCLUSIONS: Abnormal expression of the E-cadherin-catenin complex
      occurs frequently in gastric carcinoma. The close correlation with poor survival
      suggests that abnormal beta-catenin may be a useful prognostic marker.

PMID- 8978343
TI  - Repetitive sigmoid stimulation induces rectal hyperalgesia in patients with
      irritable bowel syndrome.
AB  - BACKGROUND & AIMS: Only a fraction of patients with irritable bowel syndrome
      (IBS) show hypersensitivity to rectal distention. The current study sought to
      determine if repetitive high-pressure stimulation of sigmoid mechanoreceptors
      modulates perception of rectal pain and discomfort. METHODS: In 14 patients with
      IBS and 11 healthy controls, perception thresholds for discomfort and pain during
      rectal sensory tracking and verbal descriptor ratings of the perceived intensity
      of a rectal tonic stimulus were obtained before and after repetitive high
      pressure mechanical sigmoid stimulation. Gastrointestinal and psychological
      symptoms were assessed by questionnaires. RESULTS: Despite heterogeneity in
      baseline rectal sensitivity in patients with IBS, after sigmoid stimulation, 100%
      of patients, regardless of baseline sensitivity, developed rectal hyperalgesia
      manifested by at least two of the following three criteria: lowered thresholds
      for pain and discomfort and increased viscerosomatic referral and lower abdominal
      discomfort outlasting the experimental stimulation. This pattern of responses was
      not observed in any of the healthy controls. CONCLUSIONS: In patients with IBS,
      repetitive stimulation of sigmoid splanchnic afferents results in the development
      of central sensitization manifested as hyperalgesia and increased viscerosomatic
      referral during rectal distention and as spontaneous rectosigmoid hyperalgesia in
      the absence of applied stimuli. Repetitive sigmoid contractions may induce
      rectosigmoid hyperalgesia in patients with IBS.

PMID- 8978344
TI  - Regional cerebral activity in normal and pathological perception of visceral
      pain.
AB  - BACKGROUND & AIMS: To characterize the cerebral processing of noxious visceral
      events, changes in regional cerebral blood flow associated with perception of
      intestinal pain were examined. METHODS: The effects of rectal pressure stimuli on
      regional cerebral blood flow were assessed with 15O-water positron emission
      tomography (PET) in 12 subjects, half with irritable bowel syndrome (IBS). PET
      scans were obtained at baseline and during both actual and simulated delivery of
      anticipated stimuli. Changes in regional cerebral blood flow were interpreted
      using statistical parametric mapping and region of interest methods of analysis.
      RESULTS: In healthy subjects, perception of pain during actual or simulated
      delivery of painful stimuli was significantly associated (P < 0.01) with activity
      of the anterior cingulate cortex (ACC; Brodmann's areas 24 and 32), whereas no
      ACC response to perception of nonpainful stimuli was observed. In patients with
      IBS, the ACC failed to respond to the same stimuli, whereas significant
      activation (P < 0.01) of the left prefrontal cortex (maximal in Brodmann's area
      10) was seen. CONCLUSIONS: The perception of acute rectal pain is associated with
      activation of the ACC in healthy subjects, and patients with IBS show an aberrant
      brain activation pattern both during noxious rectal distention and during the
      anticipation of rectal pain.

PMID- 8978345
TI  - Coordination of deglutitive glottal function and pharyngeal bolus transit during
      normal eating.
AB  - BACKGROUND & AIMS: Deglutitive glottal function during the preparatory phase of
      swallowing and its coordination with bolus transit during normal eating are
      important for airway protection. The aim of this study was to examine this
      coordination during consumption of a normal meal. METHODS: Fifteen healthy
      volunteers were studied using a videoendoscopic and videofluoroscopic technique.
      RESULTS: A total of 207 liquid and 470 solid bolus swallows were analyzed. In 60%
      of liquid and 76% of solid food swallows, the bolus was seen in the pharynx
      before a swallow was initiated. Entry of boluses into the pharynx was associated
      with brief partial adduction of the vocal cords. Solid food entered and traversed
      the pharynx at the midline, whereas liquid bolus was split around the larynx and
      rejoined in the hypopharynx. Swallowing was initiated significantly earlier when
      bolus made contact with the upper third of the epiglottis compared with vallecula
      or pyriform sinuses. CONCLUSIONS: In more than half of the instances, during
      normal eating, food enters the pharynx during the preparatory phase before a
      swallow is initiated, the path of pharyngeal transit of solid bolus is different
      from that of liquid bolus, and the epiglottal edge appears to be the most
      sensitive trigger zone for swallowing.

PMID- 8978346
TI  - Studies on the interrelation between Zollinger-Ellison syndrome, Helicobacter
      pylori, and proton pump inhibitor therapy.
AB  - BACKGROUND & AIMS: The interrelation between Helicobacter pylori infection and
      proton pump inhibitor therapy in patients with Zollinger-Ellison syndrome is
      unknown. The aim of this study was to evaluate the influence of these factors on
      parameters of Zollinger-Ellison syndrome. METHODS: Prevalence of H. pylori was
      determined by biopsy and antibody testing in 84 patients. The influence of H.
      pylori status on clinical and laboratory parameters of Zollinger-Ellison syndrome
      was evaluated. Seroconversion after surgery was assessed retrospectively in
      infected patients. RESULTS: The prevalence of H. pylori exposure was 23% (10%
      with active infection). Acid output was higher in H. pylori-negative patients,
      but other clinical and biochemical parameters did not differ. Parameters were
      also similar for patients determined to be H. pylori positive by histology or
      antibody testing alone. Seroconversion rates did not differ between those
      rendered or not rendered disease free despite a significant reduction in acid
      output. CONCLUSIONS: H. pylori infection is not a risk factor for peptic
      ulceration in patients with Zollinger-Ellison syndrome. The prevalence is lower
      than in the general population and much lower than for patients with idiopathic
      peptic ulcer disease. Long-term omeprazole therapy in H. pylori-positive patients
      with Zollinger-Ellison syndrome may-lead to a reduction in parietal cell mass.

PMID- 8978347
TI  - Clinical and pathological importance of heterogeneity in vacA, the vacuolating
      cytotoxin gene of Helicobacter pylori.
AB  - BACKGROUND & AIMS: vacA encodes the vacuolating cytotoxin of Helicobacter pylori
      and exhibits marked variation in signal sequence and midgene coding regions. The
      implications for gastroduodenal pathology are unknown. The aim of this study was
      to define the association of vacA genotype with gastric inflammation and injury,
      in vitro cytotoxin activity, and peptic ulceration. METHODS: Sixty-one
      consecutive dyspeptic patients underwent endoscopy and gastric biopsy. The biopsy
      specimens were processed for H. pylori culture, and 52 specimens were also
      processed for histology. H. pylori vacA was typed by polymerase chain reaction
      and colony hybridization. Cytotoxin activity was assessed by a HeLa cell
      vacuolation assay. RESULTS: vacA signal sequence type s1a strains were associated
      with greater antral mucosal neutrophil and lymphocyte infiltration than s1b or s2
      strains (P < 0.05). vacA midregion type m1 strains were associated with greater
      gastric epithelial damage than m2 strains (P < 0.05). Both midregion and signal
      sequence were associated with cytotoxin activity in vitro. Duodenal ulcer disease
      occurred in 89% of 18 patients with s1a strains vs. 29% of 14 with s1b strains (P
      < 0.01), 20% of 10 with s2 strains (P < 0.001), and 16% of 19 uninfected patients
      (P < 0.001). CONCLUSIONS: H. pylori strains of vacA signal sequence type s1a are
      associated with enhanced gastric inflammation and duodenal ulceration. vacA s2
      strains are associated with less inflammation and lower ulcer prevalence.

PMID- 8978348
TI  - The toxin of diarrheic shellfish poisoning, okadaic acid, increases intestinal
      epithelial paracellular permeability.
AB  - BACKGROUND & AIMS: Diarrhea associated with shellfish poisoning is poorly
      understood. The responsible toxin, dinophysistoxin 1, has been identified as
      okadaic acid, a potent phosphatase inhibitor, but its effects on intestinal
      epithelia have not been examined. The aim of this study was to investigate the
      effect of okadaic acid on intestinal epithelial function, both Cl- secretion and
      barrier function. METHODS: Cultured human intestinal epithelial T84 cell
      monolayers were used. The effect of okadaic acid on these monolayers was assessed
      by measuring electrophysiological parameters, lactate dehydrogenase release, and
      22Na+ and [3H]mannitol flux rates. Protein phosphorylation studies were performed
      to identify potentially involved proteins. RESULTS: Okadaic acid does not
      directly stimulate Cl- secretion from intestinal epithelial cells. On the
      contrary, the response to well-characterized secretagogues is attenuated by
      okadaic acid. However, it does decrease transepithelial electrical resistance in
      a polarized fashion without inducing cytotoxicity. Sodium-mannitol flux studies
      suggest that the observed decrease in resistance is attributable to an increase
      in paracellular permeability. CONCLUSIONS: Okadaic acid, the toxin responsible
      for diarrheic shellfish poisoning, does not stimulate Cl- secretion but increases
      the paracellular permeability of intestinal epithelia. This alteration in
      intestinal epithelial physiology may contribute to the diarrhea of shellfish
      poisoning.

PMID- 8978349
TI  - Nonsteroidal anti-inflammatory drug enteropathy in rats: role of permeability,
      bacteria, and enterohepatic circulation.
AB  - BACKGROUND & AIMS: The pathogenesis of nonsteroidal anti-inflammatory drug
      (NSAID)-induced small intestinal damage remains poorly understood. The aim of
      this study was to examine the relative importance of the three suggested
      components of the pathogenesis of NSAID enteropathy, namely, epithelial
      permeability, enteric bacterial numbers, and enterohepatic recirculation, using
      an NSAID derivative (nitrofenac) that does not cause small intestinal damage.
      METHODS: Rats were given diclofenac or nitrofenac at 12-hour intervals.
      Epithelial permeability to [51Cr]-ethylenediaminetetraacetic acid and enteric
      bacterial numbers were determined after 1-4 doses of the drugs. Serum levels and
      biliary excretion of the two drugs were determined by high-performance liquid
      chromatography. RESULTS: Diclofenac caused a progressive increase in epithelial
      permeability, marked increases in enteric gram-negative bacterial numbers, and
      frank intestinal ulceration. Nitrofenac caused similar changes in intestinal
      permeability after a single dose but no further increase with repeated
      administration. Moreover, nitrofenac had no effect on enteric bacterial numbers
      and did not cause frank ulceration. Unlike diclofenac, nitrofenac did not undergo
      extensive enterohepatic recirculation. Two other NSAIDs that do not undergo
      enterohepatic recirculation (nabumetone and aspirin) also did not modify enteric
      bacterial numbers or cause intestinal ulceration. CONCLUSIONS: Enterohepatic
      recirculation of NSAIDs is of paramount importance in the pathogenesis of
      enteropathy caused by these drugs, whereas suppression of prostaglandin synthesis
      is relatively unimportant.

PMID- 8978350
TI  - Glutamine depletion and increased gut permeability in nonanorectic, non-weight
      losing tumor-bearing rats.
AB  - BACKGROUND & AIMS: Glutamine is an essential amino acid for rapidly dividing
      cells such as enterocytes. The progress of cancer is associated with a decrease
      of arterial and muscle glutamine concentrations. The aim of this study was to
      test whether increasing tumor loads affect gut intracellular glutamine handling,
      protein turnover, and gut absorptive and barrier function. METHODS:
      Methylcholantrene-induced tumor-bearing rats were studied with a subcutaneous
      tumor load of 5%-15% or 15%-30% of body weight. Portal drained visceral net
      uptake or release of energy substrates, amino acids, and intestinal protein
      turnover were studied. Gut absorptive capacity and permeability was assessed by
      the urinary recovery of 3-O-methyl-D-glucose or lactulose-rhamnose ratio after an
      oral gavage. RESULTS: In tumor-bearing rats, the net uptake of energy substrates
      (ketones and glutamine) and net protein synthesis increased across the portal
      drained viscera, whereas mucosal glutamine concentrations decreased. Absorptive
      capacity remained unchanged in both tumor-bearing groups. However, the lactulose
      rhamnose ratio increased with increasing tumor load, indicating loss of gut
      barrier function. This was not related to changes in villus height, crypt depth,
      or changes in mucosal cell populations but to decreased intracellular polyamine
      concentrations. CONCLUSIONS: The presence of a methylcholantrene tumor leads to
      altered mucosal glutamine metabolism and loss of gut barrier function possibly
      related to disturbed proliferation or differentiation of enterocytes.

PMID- 8978351
TI  - Peptide YY inhibition of rat gastric enterochromaffin-like cell function.
AB  - BACKGROUND & AIMS: The cellular target for peptide YY (PYY) inhibition of gastric
      acid secretion is unknown. The aim of this study was to determine whether PYY
      inhibits histamine release from isolated enterochromaffin-like (ECL) cells by
      stimulation of a selective Y receptor. METHODS: Isolated rat gastric ECL cells
      were analyzed in short-term culture for histamine release and for changes in
      intracellular calcium concentration using video imaging. RESULTS: Gastrin
      stimulated histamine release was inhibited with a 50% inhibiting concentration of
      2.10(-9) mol/L. Inhibition of histamine release and of calcium entry by PYY and
      [Pro34]PYY and no effect of PYY(3-36) characterizes an inhibitory Y1 receptor
      subtype. Reverse-transcription polymerase chain reaction of ECL cell RNA showed
      that the receptor was the nontruncated Y1 isoform. The inhibitory action of PYY
      and related peptides on gastrin-stimulated histamine release and calcium
      signaling was eliminated by pretreatment with 200 ng/mL pertussis toxin. Additive
      but not synergistic inhibitory effects of PYY and somatostatin on gastrin
      stimulated histamine release were observed. CONCLUSIONS: Activation of a Y1
      inhibitory receptor subtype present on the gastric ECL cell that inhibits gastrin
      induced ECL cell histamine release and Ca2+ entry by activation of a Gi or G(o)
      class of protein may account for inhibition of gastric acid secretion by PYY
      released from the small intestine.

PMID- 8978352
TI  - Effect of transforming growth factor alpha and interleukin 8 on somatostatin
      release from canine fundic D cells.
AB  - BACKGROUND & AIMS: Helicobacter pylori infection in patients who have peptic
      ulcer disease is associated with altered regulation of gastric secretion,
      hypergastrinemia, and diminished somatostatin expression in gastric mucosa. Tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-8 are the predominant cytokines
      produced in the gastric mucosa of patients with H. pylori infection. The aim of
      this study was to examine whether IL-8 and TNF-alpha could regulate somatostatin
      release from isolated canine gastric D cells. METHODS: Canine gastric D cells
      were isolated from fundic mucosa and enriched by centrifugal elutriation.
      Secretagogue-stimulated somatostatin release was measured by radioimmunoassay.
      RESULTS: TNF-alpha dose dependently increased somatostatin release after 2 hours
      of treatment. The stimulatory effect of TNF-alpha was additive to that of
      epinephrine but was unaffected by a maximal concentration of cholecystokinin. IL
      8 did not alter basal or secretagogue (cholecystokinin, epinephrine)-mediated
      somatostatin release. The stimulatory effect of TNF-alpha (10 ng/mL) was
      potentiated by the addition of IL-8 (1 nmol/L), inhibited by octreotide and
      staurosporine, but unaffected by indomethacin. Pretreatment of D cells with TNF
      alpha (10 ng/mL) for 24 hours abolished the subsequent stimulatory effect of this
      cytokine and secretagogues on somatostatin release. CONCLUSIONS: TNF-alpha was
      shown to regulate somatostatin release from cultured D cells in a divergent
      manner.

PMID- 8978353
TI  - Development of c-Kit-positive cells and the onset of electrical rhythmicity in
      murine small intestine.
AB  - BACKGROUND & AIMS: Little is known about the development of interstitial cells
      (ICs), yet these cells are important in electrical rhythmicity and
      neurotransmission in the gastrointestinal tract. This study characterized the
      development of ICs and the onset of electrical rhythmicity in the murine
      intestine. METHODS: Antibodies against c-Kit (e.g., the receptor for stem cell
      factor) were used to label ICs of the small intestines of embryos and neonatal
      mice. Labels for enteric neuroblasts and smooth muscle cells were used to study
      neighboring cells. Development was examined also with electron microscopy and
      electrophysiological techniques. RESULTS: c-Kit-like immunoreactivity (c-Kit-LI)
      was detected in gastrointestinal tissues at embryonic day 12.5. Labeled cells
      were distributed along the outer perimeter of the intestine and had morphological
      features of neither smooth muscle cells nor ICs. Cells with c-Kit-LI were
      nonneural and seemed to be common precursors for longitudinal muscle cells and
      ICs of the myenteric plexus region (IC-MY). Longitudinal muscle cells lost c-Kit
      by E18, whereas IC-MY continued c-Kit expression into adulthood. Electrical
      rhythmicity developed after IC-MY, and longitudinal muscle cells became separate
      entities. ICs in the deep muscular plexus region developed after birth.
      CONCLUSIONS: ICs have a nonneural origin. Common precursors yield IC-MY and
      longitudinal muscle cells. Development of IC-MY correlates with the initiation of
      electrical rhythmicity.

PMID- 8978354
TI  - The mechanism of altered neural function in a rat model of acute colitis.
AB  - BACKGROUND & AIMS: Distal colitis induced in rats by trinitrobenzene sulfonic
      acid (TNBS) causes a suppression of [3H]noradrenaline release from the myenteric
      plexus, of inflamed distal colon, as well as in noninflamed regions of colon and
      ileum. The aim of this study was to explore the mechanisms underlying these
      neural changes in TNBS colitis. METHODS: Colitis was induced by intrarectal
      administration of TNBS, and the animals were killed on day 5. Inflammation was
      assessed by measuring myeloperoxidase (MPO) activity, and noradrenaline release
      was measured as 3H release from rats myenteric plexus preparations preloaded with
      [3H]noradrenaline. These end points were examined: (1) after administration of
      the locally active steroid budesonide; (2) in congenitally athymic rats; and (3)
      in rats treated with the interleukin 1 receptor antagonist (IL-1ra) to
      interleukin 1 beta. RESULTS: In colitis, both topical budesonide and systemic IL
      1ra treatments attenuated the suppression of KCl-evoked 3H release from
      longitudinal muscle myenteric plexus in both inflamed and noninflamed segments.
      However, neither of these treatments altered MPO activity. A similar suppression
      of [3H]noradrenaline release was observed in athymic rats after TNBS, although
      there was a substantially greater increase in MPO activity compared with euthymic
      rats with colitis. CONCLUSIONS: TNBS-induced colitis alters myenteric nerve
      function at inflamed and noninflamed sites via a steroid-sensitive and
      interleukin 1-mediated process that does not require T lymphocytes.

PMID- 8978355
TI  - Phenotypes of B and T cells in human intestinal and mesenteric lymph.
AB  - BACKGROUND & AIMS: Cells in lymph draining the human gut have not been
      characterized previously. The aim of this study was to phenotype B and T cells
      present in microlymphatics of Peyer's pathces and in mesenteric lymph. METHODS:
      The studies were conducted by multicolor immunohistochemistry, flow cytometry,
      and immunocytochemistry. RESULTS: In decreasing order of frequency,
      microlymphatics in Peyer's patches contained naive T (CD3+CD45RA+ alpha 4 beta
      7low) and B (sIgD+CD20+ alpha 4 beta 7low) lymphocytes, memory T (CD45RO+ alpha 4
      beta 7+) and B (sIgD-CD20+ alpha 4 beta 7+) lymphocytes, and B-cell blasts
      (CD19+CD38high alpha 4 beta 7high). Naive cells were usually positive for L
      selectin, memory cells were either positive or negative, and B-cell blasts were
      usually negative. Mesenteric lymph contained naive T (approximately 60%) and B
      (approximately 25%) lymphocytes, memory T and B lymphocytes (approximately 10%),
      and B-cell blasts (approximately 2%). Cytospins confirmed these results and
      showed, in addition, that B-cell blasts contained cytoplasmic immunoglobulin (Ig)
      A, IgM, or IgG in overall proportions of 5:1: < 0.5. CONCLUSIONS: Our results are
      similar to the phenotypes previously described in animal thoracic or mesenteric
      lymph. A fraction of the B cells stimulated in Peyer's patches are near terminal
      differentiation (contain cytoplasmic Ig) before they enter peripheral blood. Many
      memory cells, and most if not all B-cell blasts entering lymph show an adhesion
      molecule profile (alpha 4 beta 7high L-selectin low) in keeping with the presumed
      phenotype of lymphoid cells destined for mucosal effector sites such as the gut
      lamina propria.

PMID- 8978356
TI  - The Na+/H+ exchange isoform NHE3 regulates basal canine ileal Na+ absorption in
      vivo.
AB  - BACKGROUND & AIMS: Three different Na+/H+ exchange isoforms have been localized
      in mammalian ileum: Na+/H+ exchange isoform 1 (NHE1) on the basolateral membrane
      and NHE2 and NHE3 on the brush border membrane. The aim of this study was to
      determine whether NHE3 is the predominant isoform serving basal ileal Na+
      absorption. METHODS: Immunocytochemistry was performed on canine ileum with
      specific polyclonal antibodies. Absorption studies (n = 58) were performed in
      dogs with 25-cm ileal Thiry-Vella fistulas. In groups 1-4, luminal 5-(N,N
      dimethyl)-amiloride (DMA) was administered at doses of 100 nmol/L, 5 mumol/L, and
      0.7 mmol/L to inhibit NHE1, NHE2, and NHE3, respectively. In groups 5-8, 1 mmol/L
      phlorizin (PHLZ), 0.7 mmol/L DMA, and 1 mmol/L PHLZ plus 0.7 mmol/L DMA were
      administered intraluminally. RESULTS: NHE2 and NHE3 were present in the brush
      border of canine ileal villus epithelial cells. The highest concentration of DMA
      (0.7 mmol/L) caused a significant reduction (P < 0.05) in basal ileal water and
      sodium absorption. PHLZ and 0.7 mmol/L DMA each alone significantly reduced basal
      ileal absorption (P < 0.05), whereas PHLZ plus 0.7 mmol/L DMA had an additive
      effect. CONCLUSIONS: NHE3 seems to be the Na+/H+ exchange isoform involved in the
      modulation of basal ileal water and sodium absorption. Both Na+/H+ exchange
      mediated through NHE3 and Na(+)-glucose cotransport contribute to basal ileal
      water and sodium absorption.

PMID- 8978357
TI  - The relative roles of hepatitis B and C viruses in the etiology of hepatocellular
      carcinoma in southern African blacks.
AB  - BACKGROUND & AIMS: Epidemiological studies have shown the relative roles of
      hepatitis B and C viruses in hepatocarcinogenesis to vary considerably among
      populations. The aim of this study was to define the independent and interactive
      roles of the two viruses in the genesis of hepatocellular carcinoma in southern
      African blacks. METHODS: Blood samples were taken from 231 black patients with
      hepatocellular carcinoma and matched controls treated at four Johannesburg
      hospitals. These were tested for hepatitis B surface antigen, antibodies to
      hepatitis C virus, and hepatitis C virus RNA. RESULTS: Relative to individuals
      without serological evidence of hepatitis B or C infection, those positive for
      hepatitis B surface antigen alone had a statistically significant 23.3-fold
      increased risk for hepatocellular carcinoma, whereas those positive for hepatitis
      C serology alone had a statistically significant risk of 6.6. A synergistic
      effect on risk was evident when both hepatitis B and C markers were present
      (relative risk, 82.5). Hepatitis B virus alone is estimated to cause 43% of
      hepatocellular carcinoma in southern African blacks, hepatitis C alone 5%, and
      coinfection with the two viruses 20%. CONCLUSIONS: Hepatitis B virus plays a
      predominant role in hepatocellular carcinogenesis in southern African blacks,
      with hepatitis C virus responsible for a smaller proportion of cases. Coinfection
      with the two viruses carries a synergistic risk of hepatocellular carcinoma
      formation.

PMID- 8978358
TI  - Histopathologic impact of GB virus C infection on chronic hepatitis C.
AB  - BACKGROUND & AIMS: Dual infection by hepatitis GB virus type C (GBV-C) and
      hepatitis C virus (HCV) is common. To assess the histopathologic impact of GBV-C
      infection on liver lesions, liver biopsy specimens of 105 patients chronically
      infected with HCV, 17 of whom (15%) were also infected with GBV-C, were reviewed.
      METHODS: Semiquantitative histopathologic assessment of liver lesions was
      performed using the Knodell's score and the METAVIR grading system. RESULTS:
      Hepatitis activity was mild, moderate, or severe in 3 (18%), 11 (64%), and 3
      (18%) patients, respectively, infected with GBV-C and HCV vs. 26 (29%), 56 (64%),
      and 6 (7%) patients, respectively, infected with HCV alone (no significant
      difference). Cirrhosis was present in 4 (24%) coinfected patients vs. 19 (22%)
      HCV-positive patients (no significant difference). No significant difference in
      fibrosis, presence of portal lymphoid aggregates, steatosis, and hemosiderosis
      was observed between the two groups. There was no significant difference in the
      evaluation of each item of the Knodell's score. CONCLUSIONS: This detailed
      histopathologic evaluation of GBV-C infection in chronic hepatitis C shows that
      GBV-C infection does not affect histopathologic severity and characteristics of
      chronic hepatitis C, thus suggesting a minor role of GBV-C infection in liver
      disease.

PMID- 8978359
TI  - Different cytokine profiles of intraphepatic T cells in chronic hepatitis B and
      hepatitis C virus infections.
AB  - BACKGROUND & AIMS: The cytokine pattern secreted by T cells at the site of viral
      replication may influence the final outcome of hepatitis B virus (HBV) and
      hepatitis C virus (HCV) infections. The aim of this study was to assess whether a
      cytokine imbalance oriented toward T helper (Th) 1 or Th2-type responses may play
      a role in chronic hepatitis B or C. METHODS: Production of interferon (IFN)
      gamma, interleukin (IL)-4, and IL-5 by wide series of T-cell clones derived from
      the liver of 6 patients with chronic hepatitis B (291 clones) and 9 patients with
      chronic hepatitis C (260 clones) was studied. T-cell clones were generated by
      limiting dilution from freshly isolated mononuclear cells derived from liver
      tissue to give a reliable representation of the intrahepatic inflammatory
      infiltrates. RESULTS: The majority of liver-infiltrating T cells in chronic
      hepatitis C were Th1 cells able to secrete IFN-gamma but unable to secrete IL-4
      or IL-5, whereas in hepatitis B, most CD4+ and CD8+ liver T cells were ThO-like
      cells able to produce not only IFN-gamma but also IL-4 and IL-5. CONCLUSIONS: The
      different cytokine profiles of T cells within the liver in chronic HBV and HCV
      infections illustrate a different behavior of the local immune response in these
      two infections that may have pathogenetic implications.

PMID- 8978360
TI  - Thromboxane inhibitors attenuate pathological changes in alcoholic liver disease
      in the rat.
AB  - BACKGROUND & AIMS: Thromboxane levels correlate with severity of liver injury in
      rats given alcohol. The aim of this study was to evaluate the effect of
      thromboxane inhibitors on pathological changes in experimental alcoholic liver
      disease. METHODS: Male Wistar rats were given a liquid diet and ethanol
      intragastrically for 1 month. The thromboxane inhibitors tested were a
      thromboxane receptor antagonist (TXRA) and a thromboxane synthase inhibitor
      (TXSI). Pathological changes, liver and plasma thromboxane levels, 6
      ketoprostaglandin F1 alpha levels, lipid peroxidation, and messenger RNA levels
      for tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF) beta
      were evaluated. RESULTS: Treatment with thromboxane inhibitors prevented necrosis
      and inflammation. In the TXSI-treated group, fatty liver was also decreased.
      Ethanol administration led to a 3-4-fold increase in liver thromboxane levels; a
      reduction in thromboxane levels and lipid peroxidation was seen in the TXSI
      group. In all treatment groups, TNF-alpha and TGF-beta messenger RNA levels were
      decreased. CONCLUSIONS: The prevention of necroinflammatory changes in
      thromboxane-treated groups is related to a decrease in TNF-alpha levels.
      Inhibition of TGF-beta expression may also prevent fibrosis in ethanol-treated
      rats.

PMID- 8978361
TI  - 8-Isoprostaglandin F2 alpha, a product of lipid peroxidation, increases portal
      pressure in normal and cirrhotic rats.
AB  - BACKGROUND & AIMS: The F2-isoprostanes are a recently described class of
      prostaglandins formed by free radical-mediated lipid peroxidation. 8
      Isoprostaglandin F2 alpha (8-iso-PGF2 alpha), an F2-isoprostane, has previously
      been shown to be a potent renal vasoconstrictor acting via a thromboxane-like
      receptor. The aim of this study was to investigate whether 8-iso-PGF2 alpha
      increases portal pressure. METHODS: Livers from normal and bile duct-ligated
      cirrhotic rats were perfused, and portal pressure response to infused agonist was
      monitored continuously. RESULTS: Infusion of 8-iso-PGF2 alpha increased portal
      pressure in both groups, with a significantly greater response in cirrhotic rats.
      At a dose of 2.5 nmol/min, the mean portal pressure increased from a baseline of
      8.2 +/- 0.6 to 9.8 +/- 1.3 mm Hg, whereas in cirrhotic animals, the increase was
      from 12.0 +/- 0.9 to 18.6 +/- 1.8 mm Hg. This response was completely blocked by
      SQ29548, a thromboxane receptor antagonist. A similar response pattern was
      observed with the thromboxane receptor agonist U46619. CONCLUSIONS: 8-iso-PGF2
      alpha can increase portal pressure in cirrhotic rats. If extrapolated to patients
      with cirrhosis, lipid peroxidation secondary to alcoholic liver injury, sepsis,
      or other liver pathology may cause an acute increase in portal pressure such as
      that observed in acute liver injury.

PMID- 8978362
TI  - Hepatocyte transport of bile acids and organic anions in endotoxemic rats:
      impaired uptake and secretion.
AB  - BACKGROUND & AIMS: In sepsis, intrahepatic cholestasis occurs frequently,
      suggesting impaired hepatocyte transport of bile acids and organic anions. The
      aim of the study was to define the magnitude, time course, and the site of
      impaired biliary secretion in a rat sepsis model. METHODS: Maximal transport for
      two bile acids (cholyltaurine and chenodeoxycholyltaurine) and two organic anions
      (sulfobromophthalein and sulfolithocholyltaurine) was measured in isolated
      perfused livers at various times after lipopolysaccharide injection. Basolateral
      and canalicular liver plasma membrane vesicles were used to characterize the
      impairment in hepatocyte transport. RESULTS: Maximal hepatocyte transport was
      reduced for all compounds by 60%-81% compared with controls. Bile acid
      independent bile flow was reduced by 51%. Impairment was maximal 12 hours after
      endotoxin injection and recovered thereafter. In basolateral plasma membrane
      vesicles, sodium-dependent transport for bile acids was reduced by 36%-47%.
      Sodium-independent transport of organic anions was reduced by 40%-55%. Adenosine
      triphosphate-stimulated transport was greatly decreased in canalicular vesicles
      prepared from endotoxemic animals for all four compounds probably because of a
      reduced number of transport molecules, based on kinetic studies. CONCLUSIONS:
      Basolateral and canalicular bile acid and organic anion transport are markedly
      impaired in endotoxemia. These mechanisms may contribute to the cholestasis of
      sepsis.

PMID- 8978363
TI  - Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei.
AB  - BACKGROUND & AIMS: Bile acids exert cellular and molecular effects in the liver,
      but little is known about tissue concentrations. The aim of this study was to
      characterize bile acid composition in human and rat liver tissue and hepatocyte
      nuclei and examine the effects of experimental cholestasis and bile acid
      administration. METHODS: Bile acids were measured by gas chromatography-mass
      spectrometry. RESULTS: Liver tissue concentrations of sham-operated rats were
      130.8 +/- 21.3 nmol/g, representing 2%-4% of the bile acid pool; cholic and delta
      22-beta-muricholic acids were the major bile acids identified. Concentrations
      increased 7-8-fold with bile duct ligation; deoxycholate and hyodeoxycholate
      disappeared. Lithocholate concentrations were higher in ligated rats (6.4 +/- 0.4
      vs. 3.9 +/- 0.5 nmol/g for sham-operated). Total bile acid concentrations in
      human liver tissue were 61.6 +/- 29.7 nmol/g and comprised mainly
      chenodeoxycholic and cholic acids. Concentrations were higher during
      ursodeoxycholate or tauroursodeoxycholate administration (157.2 +/- 45.6 and
      161.6 +/- 43.4 nmol/g, respectively), and liver tissue was enriched 30% in
      ursodeoxycholate at the expense of hydrophobic bile acids. Bile acids were
      identified in rat hepatic nuclei (50-110 pmol/4 x 10(7) nuclei), accounting for <
      0.1% of liver tissue levels. CONCLUSIONS: Human and rat liver tissue bile acid
      concentrations are low, increase with bile acid administration or bile duct
      ligation, and account for only a small fraction of the bile acid pool.

PMID- 8978364
TI  - Fatal hyperammonemia following orthotopic lung transplantation.
AB  - There have been anecdotes of unexplained coma and death in patients after
      otherwise successful orthotopic lung transplantation. A patient with primary
      pulmonary hypertension who underwent a technically uncomplicated single
      orthotopic lung transplantation is described. The patient developed intractable
      status epilepticus 4 days after surgery in association with the presence of a
      markedly elevated plasma ammonium level. Despite multiple therapeutic
      interventions, the hyperammonemia ultimately resulted in the patient's death.
      Both metabolic and enzymatic studies showed that the unique physiological
      disturbance in this disorder results at least in part from defective in vivo
      conversion of waste nitrogen to urea and increased production of waste nitrogen.
      Although the rate of hepatic ureagenesis was therefore insufficient to prevent
      accumulation of ammonium, the cause was not severe liver disease. Liver histology
      showed widespread, microvesicular steatosis on light-microscopic examination, but
      only electron-microscopic examination showed severe microvesicular steatosis with
      severe mitochondrial injury. As in Reye's syndrome, it was unclear whether the
      hepatic mitochondrial injury played a role in development or if it was the result
      of hyperammonemia. We recommended that any patient with an unexplained alteration
      of mental status after solid organ transplantation be evaluated for
      hyperammonemia.

PMID- 8978365
TI  - A new syndrome of Crohn's disease and pachydermoperiostosis in a family.
AB  - Few syndromic associations with Crohn's disease are described. The aim of this
      study was to characterize a new syndrome of Crohn's disease associated with
      pachydermoperiostosis in 3 brothers. Three probands, 6 siblings, both parents, 20
      of 21 third-generation relatives, and 9 spousal controls were evaluated.
      Serological evaluation for antineutrophil cytoplasmic antibodies and human
      leukocyte antigens as well as genetic testing for tumor necrosis factor
      microsatellites, intercellular adhesion molecule 1 polymorphisms, the interleukin
      1 receptor antagonist gene, and the interleukin 1 beta gene were performed. Only
      the 3 probands were affected and developed pachydermoperiostosis between ages 14
      and 17 years. Pachydermoperiostosis preceded Crohn's ileocolitis by 6 and 20
      years in two probands, excluding secondary hypertrophic osteoarthropathy. Two
      probands were antineutrophil cytoplasmic antibody positive vs. 1 of 27 unaffected
      relatives (P < 0.001, chi 2). Haplotypes for human leukocyte antigen and tumor
      necrosis factor microsatellites were discordant. The probands' generation was
      homozygous for the common allele 1 of the interleukin 1 receptor antagonist and
      interleukin 1 beta genes. Two probands carried a rare polymorphism of the
      intercellular adhesion molecule 1 gene. A new syndrome of Crohn's disease and
      pachydermoperiostosis associated with antineutrophil cytoplasmic antibodies is
      described. Inheritance is most likely autosomal recessive by pedigree. No clear
      association was found between this syndrome and the gene regions evaluated.

PMID- 8978366
TI  - Basidiobolomycosis: an unusual fungal infection mimicking inflammatory bowel
      disease.
AB  - Basidiobolus ranarum is a fungus belonging to the Entomophthoraceae family and is
      mainly associated with subcutaneous soft tissue infection. The disease is usually
      characterized by an insidious onset of massive induration of the subcutaneous
      tissue involving the limbs, trunk, or buttocks. Most cases of basidiobolomycosis
      have been reported from Africa, South America, and tropical Asia. Visceral
      involvement is extremely rare. Only 4 cases with involvement of the
      gastrointestinal tract, including 1 fatal case originating in the United States,
      have been well documented in the English-language literature. This case report
      describes the first successfully treated patient residing in the United States
      who had B. ranarum infection involving the gastrointestinal tract.

PMID- 8978367
TI  - Nonmitogenic actions of growth factors: an integrated view of their role in
      intestinal physiology and pathophysiology.

PMID- 8978368
TI  - The pathobiology of biliary epithelia.
AB  - Our understanding of the pathobiology of biliary epithelia is rapidly growing
      because of a surge of investigative activity. This became possible after suitable
      experimental models and techniques were developed with which to study
      cholangiocyte biology. Although the molecular mechanisms of bile formation by
      cholangiocytes and the role of these cells as a major cellular target in a
      variety of severe hepatobiliary diseases are currently being investigated, many
      questions remain unanswered, particularly regarding cholangiocellular functions,
      both in normal and abnormal conditions. As current experimental models become
      more refined, scientists with interests as diverse as cell biology and
      physiology, morphology, pharmacology, immunology, genetics, and oncology can be
      expected to further clarify the pathobiology of biliary epithelia.

PMID- 8978369
TI  - Abnormal gastric histology and decreased acid production in cholecystokinin
      B/gastrin receptor-deficient mice.
AB  - BACKGROUND & AIMS: The cholecystokinin (CCK)-B/gastrin receptor is one of several
      regulators of gastric acid secretion and mucosal growth. To elucidate the
      contribution of this receptor relative to other trophic and secretory factors,
      mice that lack the CCK-B/gastrin receptor have been generated and studied.
      METHODS: Both alleles of the CCK-B/gastrin receptor were inactivated by targeted
      gene disruption. Analysis of the mice included measurement of basal gastric pH
      and plasma gastrin levels. In addition, multiple gastric mucosal cell types were
      identified by immunostaining and quantified. RESULTS: Homozygous mutant mice were
      viable, fertile, and appeared grossly normal into adulthood. The receptor
      deficient mice exhibited a marked increase in basal gastric pH (from 3.2 to 5.2)
      and an approximately 10-fold elevation in plasma gastrin concentration compared
      with wild-type controls. In the stomach of mutant animals, parietal and
      enterochromaffin-like cells were decreased, providing a likely explanation for
      the reduction in acid output. In the antrum, a decrease in somatostatin cell
      density and an increase in the gastrin cell number were observed, consistent with
      the concomitant elevation in circulating gastrin. CONCLUSIONS: Together, these
      findings demonstrate the importance of the CCK-B/gastrin receptor in maintaining
      the normal cellular composition and function of the gastric mucosa.

PMID- 8978370
TI  - American Gastroenterological Association. The centennial year: the development of
      important ideas during the last 100 years.

PMID- 8978371
TI  - Liver transplantation.

PMID- 8978372
TI  - What is a gold standard for colon polyps?

PMID- 8978373
TI  - Colonoscopy and barium enema: radiologist's response.

PMID- 8978374
TI  - What's new with RII?

PMID- 8978375
TI  - Sepsis-associated cholestasis.

PMID- 8978376
TI  - Three coins in a nutrition fountain.

PMID- 8978377
TI  - Noncardiac chest pain: from nutcrackers to nociceptors.

PMID- 8978378
TI  - Gastric permeability in celiac disease.

PMID- 8978379
TI  - Alcoholic pancreatitis: from what histological starting point?

PMID- 8978380
TI  - Do pANCA define a clinical subgroup in patients with Crohn's disease?

PMID- 8978381
TI  - Apoptosis repressor genes Bcl-2 and Bcl-x-long are expressed in the rat brain
      following global ischemia.
AB  - The proto-oncogenes bcl-2 and bcl-x-long have been shown to suppress apoptotic
      cell death in a variety of in vitro systems and cell lines, including neurons. An
      alternatively spliced from of bcl-x, bcl-x-short, is a promoter of apoptotic
      death. Whether these genes are induced after ischemia or play any role in
      determining the fate of ischemic neurons is unknown. To begin to address this
      issue, we studied the expression of bcl-2, and bcl-x mRNA and protein after
      global ischemia in the rat. Ischemia was induced in isoflurane-anesthetized rats
      by the four-vessel occlusion method. mRNA expression was studied by Northern blot
      analysis at 24 h after ischemia and by in situ hybridization at 2, 4, 8, 24, and
      72 h after 15 min of global ischemia. Protein expression was studied using both
      immunocytochemistry at 4, 8, 16, 24, and 72 h after ischemia and Western blot
      analysis from tissue harvested at 16, 24, and 72 h after ischemia. Western blots
      showed that bcl-x-long is the predominant form of bcl-x protein expressed in both
      normal and ischemic brain. Both bcl-2 and bcl-x-long mRNA were expressed in CA1,
      CA3, and the molecular layer of the dentate after ischemia. However, bcl-2 and
      bcl-x protein were expressed only in CA3 and dentate. Thus, while bcl-2 and bcl-x
      long mRNA were expressed in both surviving and dying neurons, their proteins were
      expressed in neurons destined to survive. These results support potential roles
      for these two apoptosis suppressor proteins in promoting survival after cerebral
      ischemia.

PMID- 8978382
TI  - Expression of interleukin-1 beta converting enzyme gene family and bcl-2 gene
      family in the rat brain following permanent occlusion of the middle cerebral
      artery.
AB  - Recent investigations have been suggesting that some neuronal subpopulations may
      die via programmed cell death after focal ischemic injury. To clarify the
      possible roles of the genes involved in the cell-death program, this study
      examined the expression of three members of the interleukin-1 beta converting
      enzyme (Ice) gene family (Ice, Nedd2, and Yama/CPP32) and two members of the bcl
      2 gene family (bcl-2 and bcl-x) in the rat brain after permanent occlusion of the
      middle cerebral artery. Northern blot analysis revealed a transient induction of
      Nedd2 mRNA 8 h after the ischemic insult (3.8-fold) and an increase in Yama/CPP32
      mRNA 16 to 24 h after the insult (5.8-fold at 24 h), whereas the expression of
      Ice remained constant. The expression of bcl-2 and bcl-x remained constant after
      the ischemic insult. Taking into account the key role of the Ice gene family in
      the execution of programmed cell death, the induction of Ice gene family might
      play a causative role in apoptotic cell death.

PMID- 8978383
TI  - Intravenous infusion of adrenomedullin and increase in regional cerebral blood
      flow and prevention of ischemic brain injury after middle cerebral artery
      occlusion in rats.
AB  - The intravenous infusion of rat adrenomedullin, at concentrations ranging from
      0.1 to 1.0 microgram/kg/min, for 60 min increased the regional cerebral blood
      flow (rCBF) in a dose-dependent manner in rats. rCBF was measured using a laser
      Doppler flowmetry device placed on the surface of the parietal cortex. The
      increase in rCBF induced by 1.0 microgram/kg/min of adrenomedullin was up to 145
      +/- 10.8% of controls at 60 min (n = 5, p < 0.001). These concentrations of
      adrenomedullin did not affect systemic blood pressure or other physiologic
      parameters, including pH, PaCO2, PaO2, hemoglobin, and blood glucose. Repeated
      infusion of 1.0 microgram/kg/min of adrenomedullin at 2-h intervals caused
      tachyphylaxis (n = 5, p < 0.01). Rat adrenomedullin (1.0 microgram/kg/min)
      demonstrated a more potent effect than the same dose of human adrenomedullin. The
      C-terminal fragment of human adrenomedullin (0.5 and 5.0 micrograms/kg/min),
      adrenomedullin22-52, which did not affect rCBF alone, inhibited the effect of rat
      adrenomedullin (0.5 microgram/kg/min) as a receptor antagonist in a dose
      dependent manner. In a model of middle cerebral artery (MCA) occlusion in
      spontaneously hypertensive rats, pre- and postinfusion of 1.0 microgram/kg/min of
      adrenomedullin suppressed the reduction in rCBF following MCA occlusion (control,
      29 +/- 15.1%; adrenomedullin group, 45 +/- 14.4%; not significant) and decreased
      the volume of ischemic brain injury (control, 288 +/- 35 mm3; adrenomedullin
      group, 232 +/- 35 mm3; p < 0.05). These results suggest that adrenomedullin
      increases rCBF and prevents ischemic brain injury, partly by increasing the
      collateral circulation.

PMID- 8978384
TI  - Reactive astrocytosis from excitotoxic injury in hippocampal organ culture
      parallels that seen in vivo.
AB  - Reactive astrocytes influence not only the severity of brain injury, but also the
      capacity of brain to reshape itself with learning. Mechanisms responsible for
      astrogliosis remain unknown but might be best studied in vitro, where improved
      access and visualization permit application of modern molecular and cellular
      techniques. We have begun to explore whether gliosis might be studied in
      hippocampal organotypic cultures (HOTCs), where potential cell-to-cell
      interactions are preserved and the advantages of an in vitro preparation are
      still realized. Following HOTC exposure to N-methyl-D-aspartate (NMDA), dose
      dependent changes occurred in the optical density (OD) values for the astrocytic
      immunohistochemical [immunostaining (IS)] markers glial fibrillary acidic protein
      (GFAP) and vimentin. Exposure of HOTCs to NMDA (10 microM) caused selective death
      in the CA1 hippocampal region and the dentate gyrus. It also significantly
      increased GFAP IS and vimentin IS OD values in these regions. Increased GFAP IS
      and vimentin IS OD values were also seen in CA3, a hippocampal region that
      displayed no cell death. Light microscopic examination revealed hypertrophied
      GFAP and vimentin IS cells, characteristic of reactive astrocytes. Cellular
      proliferation, as assessed by proliferating cell nuclear antigen IS, was also
      significantly increased in all three of these hippocampal regions. In contrast,
      exposure of HOTCs to a noninjurious level of NMDA (1 microM) caused only minor
      changes in GFAP IS and vimentin IS OD values but a significantly reduced cellular
      proliferation in all HOTC regions. These results show that reactive astrocytosis
      from excitotoxic injury of HOTC parallels changes seen in vivo after global
      ischemia. Furthermore, since resting astroglia within HOTCs are also similar to
      their counterparts in vivo, HOTCs may be used to examine mechanisms by which
      these cells are transformed into reactive species within tissue that resembles
      intact brain.

PMID- 8978385
TI  - Methionine sulfoximine, a glutamine synthetase inhibitor, attenuates increased
      extracellular potassium activity during acute hyperammonemia.
AB  - Hyperammonemia causes glutamine accumulation and astrocyte swelling. Inhibition
      of glutamine synthesis reduces ammonia-induced edema formation and watery
      swelling in astrocyte processes. Ordinarily, astrocytes tightly control
      extracellular K+ activity [K+]e. We tested the hypothesis that acute
      hyperammonemia interferes with this tight regulation such that [K+]e increases
      and that inhibition of glutamine synthetase reduces this increase in [K+]e. Ion
      sensitive microelectrodes were used to measure [K+]e in parietal cortex
      continuously over a 6-h period in anesthetized rats. After i.v. sodium acetate
      infusion in eight control rats, plasma ammonia concentration was 33 +/- 26
      mumol/L (+/- SD) and [K+]e remained stable at 4.3 +/- 1.6 mmol/L. During ammonium
      acetate infusion in nine rats, plasma ammonia increased to 594 +/- 124 mumol/L at
      2 h and to 628 +/- 135 mumol/L at 6 h. There was a gradual increase in [K+]e from
      3.9 +/- 0.7 to 6.8 +/- 2.7 mmol/L at 2 h and 11.8 +/- 6.7 mmol/L at 6 h. In eight
      rats, L-methionine-D,L-sulfoximine (150 mg/kg) was infused 3 h before ammonium
      acetate infusion to inhibit glutamine synthetase. At 2 and 6 h of ammonium
      acetate infusion, plasma ammonia concentration was 727 +/- 228 and 845 +/- 326
      mumol/L, and [K+]e was 4.5 +/- 1.9 and 6.1 +/- 3.8 mmol/L, respectively. The
      [K+]e value at 6 h was significantly less than that obtained with ammonium
      acetate infusion alone but was not different from that obtained with sodium
      acetate infusion. We conclude that acute hyperammonemia impairs astrocytic
      control of [K+]e and that this impairment is linked to glutamine accumulation
      rather than ammonium ions per se.

PMID- 8978386
TI  - Blood glucose concentration does not affect outcome in brain trauma: A 31P MRS
      study.
AB  - Effects of blood glucose concentration on biochemical and neurologic outcome
      following lateral fluid percussion-induced traumatic injury of moderate severity
      (2.8 atm) in rats were studied using radioactive phosphorus (31P) magnetic
      resonance spectroscopy (MRS) and a battery of tests designed to evaluate
      posttraumatic neurologic motor function. Prior to injury, male Sprague-Dawley
      rats (n = 18) were randomly assigned to receive either dextrose, 2 ml 50%
      (wt/vol), zinc insulin (10 IU/kg) or no treatment, thus dividing the animals into
      hyperglycemic, hypoglycemic, and normoglycemic groups, respectively. Animals were
      then injured, monitored for 4 h by 31P MRS before being allowed to recover, and
      assessed for posttraumatic motor function. Following brain injury, there was no
      difference in brain intracellular pH between groups over the 4-h posttraumatic
      MRS monitoring period. Similarly, intracellular free magnesium, cytosolic
      phosphorylation potential, and neurologic outcome posttrauma were not
      significantly different between groups. We conclude that, unlike models of
      ischemia, blood glucose concentration may not be a significant factor affecting
      outcome in traumatic brain injury.

PMID- 8978387
TI  - Examination of potential mechanisms in the enhancement of cerebral blood flow by
      hypoglycemia and pharmacological doses of deoxyglucose.
AB  - Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited
      by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2
      deoxyglucose (DG). The present studies in unanesthetized rats with insulin
      induced hypoglycemia show that the increases in CBF, measured with the
      [14C]iodoantipyrine method, are relatively small until arterial plasma glucose
      levels fall to 2.5 to 3.0 mM, at which point CBF rises sharply. A direct effect
      of insulin on CBF was excluded; insulin administered under euglycemic conditions
      maintained by glucose injections had no effects on CBF. Insulin administration
      raised plasma lactate levels and decreased plasma K+ and HCO3- concentrations and
      arterial pH. These could not, however, be related to the increased CBF because
      insulin under euglycemic conditions had similar effects without affecting CBF;
      furthermore, the inhibition of brain glucose metabolism with pharmacological
      doses (200 mg/kg intravenously) of DG increased CBF, just like insulin
      hypoglycemia, without altering plasma lactate and K+ levels and arterial blood
      gas tensions and pH. Nitric oxide also does not appear to mediate the increases
      in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p.
      injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single
      i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic,
      hypoglycemic, and DG-treated rats but did not significantly reduce the increases
      in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3
      mM) or pharmacological doses of deoxyglucose.

PMID- 8978388
TI  - A model for the coupling between cerebral blood flow and oxygen metabolism during
      neural stimulation.
AB  - A general mathematical model for the delivery of O2 to the brain is presented,
      based on the assumptions that all of the brain capillaries are perfused at rest
      and that all of the oxygen extracted from the capillaries is metabolized. The
      model predicts that disproportionately large changes in blood flow are required
      in order to support small changes in the O2 metabolic rate. Interpreted in terms
      of this model, previous positron emission tomography (PET) studies of the human
      brain during neural stimulation demonstrating that cerebral blood flow (CBF)
      increases much more than the oxygen metabolic rate are consistent with tight
      coupling of flow and oxidative metabolism. The model provides a basis for the
      quantitative interpretation of functional magnetic resonance imaging (fMRI)
      studies in terms of changes in local CBF.

PMID- 8978389
TI  - Cerebral [15O] water clearance in humans determined by positron emission
      tomography: II. Vascular responses to vibrotactile stimulation.
AB  - When used to measure blood flow, water leaves a residue in the vascular bed,
      which may contribute to the calculation of increased blood flow during functional
      activation of brain tissue. To assess the magnitude of this contribution with the
      two-compartment positron emission tomography (PET) method, we mapped the water
      clearance (K1) of the brain as an index of cerebral blood flow (CBF) and the
      apparent vascular distribution of nonextracted H2 15O (Vo). The latter map
      represented mainly the cerebral arterial and arteriolar volume. We also prepared
      subtraction maps (delta K1, delta Vo) of the response to vibrotactile stimulation
      of the fingertips of the right hand of six normal volunteers. Using magnetic
      resonance (MR) images of all subjects, the data were rendered into Talairach's
      stereotaxic coordinates and the averaged subtraction images (activation minus
      baseline) merged with the corresponding averaged MRI image. The delta K1 map
      revealed the expected response in the primary sensory hand area; the delta Vo
      response was located about 13 mm more anteriorly, close to the central fissure,
      most likely reflecting changes of the arteries feeding the primary sensory hand
      area. We conclude that cerebral perfusion and cerebrovascular responses to
      vibrotactile stimulation may occur in disparate locations that can be identified
      separately by using the two-compartment method.

PMID- 8978390
TI  - Analysis of dynamic radioligand displacement or "activation" studies.
AB  - We present a simple way of assessing dynamic or time-dependent changes in
      displacement during single-subject radioligand positron emission tomography (PET)
      activation studies. The approach is designed to facilitate dynamic activation
      studies using selective radioligands. These studies are, in principle, capable of
      characterising functional neurochemistry by analogy with the study of functional
      neuroanatomy using rCBF activation studies. The proposed approach combines time
      dependent compartmental models of tracer kinetics and the general linear model
      used in statistical parametric mapping. This provides for a comprehensive, voxel
      based and data-led assessment of regionally specific effects. The statistical
      model proposed in this paper is predicated on a single-compartment model extended
      to allow for time-dependent changes in kinetics. We have addressed the
      sensitivity and specificity of the analysis, as it would be used operationally,
      by applying the analysis to 11C-Flumazenil dynamic displacement studies. The
      activation used in this demonstration study was a pharmacological (i.v.
      midazolam) challenge, 30 min after administration of the tracer. We were able to
      demonstrate, and make statistical inferences about, regional increases in k2 (or
      decreases in the volume of distribution) in prefrontal and other cortical areas.

PMID- 8978391
TI  - Nitric oxide of neuronal origin is involved in cerebral blood flow increase
      during seizures induced by kainate.
AB  - In a previous study, we reported that the sustained increase in CBF concomitant
      with seizures induced by kainate is mainly due to the potent vasodilator nitric
      oxide (NO). However, the production site of NO acting at cerebral vessels was
      undetermined. In the present study, we investigated whether NO responsible for
      the cerebral vasodilation is of either neuronal or endothelial origin. We used a
      putative selective inhibitor of neuronal NO synthase, 7-nitro indazole (7-NI).
      CBF was measured continuously in parietal cortex by means of laser Doppler
      flowmetry in awake rats. Systemic variables and electroencephalograms were
      monitored. Kainate (10 mg/kg i.p.) was given to rats previously treated with
      saline (n = 8) or 7-NI (25 mg/kg i.p., n = 8) or L-arginine (300 mg/kg i.p., n =
      8) followed 30 min later by 7-NI (25 mg/kg i.p.). Under basal conditions, 7-NI
      decreased CBF by 27% without modifying the mean arterial blood pressure. Under
      kainate, 7-NI prevented significant increases in CBF throughout the seizures
      despite sustained paroxysmal electrical activity. L-arginine, the substrate in
      the production of NO, prevented any decrease in CBF under 7-NI in basal
      conditions and partially, but nonsignificantly, reversed the cerebrovascular
      influence of 7-NI during seizures. In a separate group of rats (n = 6),
      inhibition of cortical NO synthase activity by 7-NI was assayed at 73%. The
      present results show that neurons are the source of NO responsible for the
      cerebrovascular response to seizure activity after kainate systemic injection.

PMID- 8978392
TI  - Role of nitric oxide, cyclic nucleotides, and the activation of ATP-sensitive K+
      channels in the contribution of adenosine to hypoxia-induced pial artery
      dilation.
AB  - Previously, it had been observed that nitric oxide (NO) contributes to hypoxia
      induced pial artery dilation in the newborn pig. Additionally, it was also noted
      that activation of ATP-sensitive K+ channels (KATP) contribute to cGMP-mediated
      as well as to hypoxia-induced pial dilation. Although somewhat controversial,
      adenosine is also thought to contribute to hypoxic cerebrovasodilation. The
      present study was designed to investigate the role of NO, cyclic nucleotides, and
      activation of KATP channels in the elicitation of adenosine's vascular response
      and relate these mechanisms to the contribution of adenosine to hypoxia-induced
      pial artery dilation. The closed cranial window technique was used to measure
      pial diameter in newborn pigs. Hypoxia-induced artery dilation was attenuated
      during moderate (PaO2 approximately 35 mm Hg) and severe hypoxia (PaO2
      approximately 25 mm Hg) by the adenosine receptor antagonist 8-phenyltheophylline
      (8-PT) (10(-5) M) (26 +/- 2 vs. 19 +/- 2 and 34 +/- 2 vs. 22 +/- 2% for moderate
      and severe hypoxia in the absence vs. presence of 8-PT, respectively). This
      concentration of 8-PT blocked pial dilation in response to adenosine (8 +/- 2, 16
      +/- 2, and 23 +/- 2 vs. 2 +/- 2, 4 +/- 2, and 6 +/- 2% for 10(-8), 10(-6), and
      10(-4) M adenosine before and after 8-PT, respectively). Similar data were also
      obtained using adenosine deaminase as a probe for the role of adenosine in
      hypoxic pial dilation. Adenosine-induced dilation was associated with increased
      CSF cGMP concentration (390 +/- 11 and 811 +/- 119 fmol/ml for control and 10(-4)
      M adenosine, respectively). The NO synthase inhibitor, L-NNA, and the cGMP
      antagonist, Rp 8-bromo cGMPs, blunted adenosine-induced pial dilation (8 +/- 1,
      14 +/- 1, and 20 +/- 3 vs. 3 +/- 1, 5 +/- 1, and 8 +/- 3% for 10(-8), 10(-6), and
      10(-4) M adenosine before and after L-NNA, respectively). Adenosine dilation was
      also blunted by glibenclamide, a KATP antagonist (9 +/- 2, 14 +/- 3, 21 +/- 4 vs.
      4 +/- 1, 8 +/- 2, and 11 +/- 2% for 10(-8), 10(-6), and 10(-4) M adenosine before
      and after glibenclamide, respectively). Finally, it was also observed that
      adenosine-induced dilation was associated with increased CSF cAMP concentration
      and the cAMP antagonist, Rp 8-bromo cAMPs, blunted adenosine pial dilation. These
      data show that adenosine contributes to hypoxic pial dilation. These data also
      show that NO, cGMP, cAMP, and activation of KATP channels all contribute to
      adenosine induced pial dilation. Finally, these data suggest that adenosine
      contributes to hypoxia-induced pial artery dilation via cAMP and activation of
      KATP channels by NO and cGMP.

PMID- 8978393
TI  - Developmental and regional differences in nitric oxide synthase activity and
      blood flow in the sheep brain.
AB  - Nitric oxide synthase (NOS) participates in the regulation of cerebral blood flow
      and neurotransmitter release and as a second messenger of glutamatergic and
      cholinergic systems. Developmental differences in NOS activity have been
      described in the rat, but not in a species with longer gestation and a larger,
      lobulated brain at birth. We assayed NOS activity by conversion of [14C]L
      arginine to [14C]L-citrulline in 50-mg tissue samples from eight brain regions in
      sheep at 70, 92, 110, and 135 days gestation (term = 145 days); newborns (< 7
      days); and adults to test the hypothesis that NOS activity in the brain is
      developmentally regulated from midgestation through adulthood and matures along
      the neuroaxis in parallel with the known development of cerebral blood flow and
      neuronal activity. Three patterns of maturation of NOS activity were evident:
      increasing to or exceeding adult levels before 70 days gestation in the thalamus,
      cerebellum, and medulla; increasing to adult levels between 70 and 92 days in the
      hippocampus; and increasing to adult levels after 92 days in the cortex and
      caudate. Additionally, there were regional differences in cortical NOS activity:
      at 70 and 92 days of gestation, frontal cortex NOS activity was greater than
      parietal or occipital activity, and at 135 days gestation and in the newborn and
      adult, cortical and caudate activity exceeded that in most of the more caudal
      regions. The up to fourfold increase in regional cortical NOS activity between 92
      and 135 days gestation was associated with twofold increases in cerebral blood
      flow and oxygen consumption during this period. Inhibition of NOS activity with
      administration of 60 mg/kg of NG-nitro-L-arginine methylester (L-NAME) resulted
      in 27% and 25% reductions in cerebral blood flow at 93 and 133 days gestation.
      While the associated increases in NOS activity with increases in CBF and CMRO2 do
      not appear causative, at various points in gestation the development of NOS
      activity may participate in the development of mature patterns of cerebral blood
      flow regulation in parallel with development of synaptic and electrical activity.

PMID- 8978394
TI  - Positron emission tomography for quantitative determination of glucose metabolism
      in normal and ischemic brains in rats: an insoluble problem by the Harderian
      glands.
AB  - To examine the reliability of quantitative positron emission tomography studies
      in the rat (Rat-PET), we assessed the influence of radioactivity accumulated in
      the Harderian glands on PET CMRglc determination. We measured CMRglc by PET and
      ex vivo dissection methods by using 2-[18F]fluoro-2-deoxy-D-glucose in rats with
      and without focal brain ischemia. The CMRglc values obtained by PET, after
      correcting with recovery coefficients, were higher than those measured by the ex
      vivo method at rostral slices, and reduction of the CMRglc in the ischemic brain
      was not demonstrated by PET in the frontal cortex. The radioactivity accumulated
      in the Harderian glands prevents the quantitative determination of CMRglc using
      Rat-PET.

PMID- 8978395
TI  - Society for the Study of Fertility and Dutch-Flemish Fertility Society joint
      winter meeting. Ghent, 1996. abstracts.

PMID- 8978396
TI  - Androgen-induced redox changes in prostate cancer cells: what are causes and
      effects?

PMID- 8978397
TI  - Indoor radon exposure and lung cancer: risky or not?--all over again.

PMID- 8978398
TI  - Ashkenazim not alone: other ethnic groups have breast cancer gene mutations, too.

PMID- 8978399
TI  - Cancer Genetics Network gets under way with 5 years of funding.

PMID- 8978400
TI  - New diagnostic criteria for HNPCC are on the way.

PMID- 8978401
TI  - Algorithms vie for diagnostic role in prostate cancer.

PMID- 8978403
TI  - Chronic care crisis: escalating cost and incidence.

PMID- 8978402
TI  - Preparing for life's end: do health professionals need more training?

PMID- 8978404
TI  - Gene therapy for cancer: what have we done and where are we going?
AB  - Gene-based therapies for cancer in clinical trials include strategies that
      involve augmentation of immunotherapeutic and chemotherapeutic approaches. These
      strategies include ex vivo and in vivo cytokine gene transfer, drug sensitization
      with genes for prodrug delivery, and the use of drug-resistance genes for bone
      marrow protection from high-dose chemotherapy. Inactivation of oncogene
      expression and gene replacement for tumor suppressor genes are among the
      strategies for targeting the underlying genetic lesions in the cancer cell. A
      review of clinical trial results to date, primarily in patients with very
      advanced cancers refractory to conventional treatments, indicates that these
      treatments can mediate tumor regression with acceptably low toxicity. Vector
      development remains a critical area for future research. Important areas for
      future research include modifying viral vectors to reduce toxicity and
      immunogenicity, increasing the transduction efficiency of nonviral vectors,
      enhancing vector targeting and specificity, regulating gene expression, and
      identifying synergies between gene-based agents and other cancer therapeutics.

PMID- 8978405
TI  - Prooxidant-antioxidant shift induced by androgen treatment of human prostate
      carcinoma cells.
AB  - BACKGROUND: Prostate cancer is a disease associated with aging. Also commonly
      associated with increasing age is a shift in the prooxidant-antioxidant balance
      of many tissues toward a more oxidative state, i.e., increased oxidative stress.
      We hypothesize that androgen exposure, which has long been associated with the
      development of prostate cancer, may be a means by which the prooxidant
      antioxidant balance of prostate cells is altered. PURPOSE: Using established
      prostate carcinoma cell lines, we studied the effect of androgens on various
      parameters of oxidative state (e.g., generation of hydrogen peroxide and hydroxyl
      radicals, lipid peroxidation, and oxygen consumption) and antioxidant defense
      mechanisms (e.g., the glutathione system and catalase). METHODS: The androgen
      responsive LNCaP and the androgen-independent DU145 prostate carcinoma cell lines
      were exposed to 5 alpha-dihydrotestosterone (DHT) and to the synthetic androgen
      R1881. The cellular proliferation responses were measured by use of a
      fluorometric assay to quantitate the amount of DNA. The generation of reactive
      oxygen species was measured by use of 2',7'-dichlorofluorescin diacetate, a dye
      that fluoresces in the presence of hydrogen peroxide or hydroxyl radicals. Lipid
      peroxidation was quantitated by use of a chromogen specific for malonaldehyde and
      4-hydroxy-2(E)-nonenal. General mitochondrial activity was determined by assaying
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. A
      Clark-type electrode was used to assess oxygen consumption per cell.
      Intracellular glutathione concentrations and the activities of catalase and gamma
      glutamyl transpeptidase were measured spectrophotometrically. All P values
      resulted from two-sided tests. RESULTS: DHT at less than 1 to 100 nM (a
      concentration range encompassing the physiologic levels of DHT considering all
      ages) and R1881 at 0.1-1 nM concentrations were effective in inducing in LNCaP
      cells comparable proliferative responses and changes in oxidative stress. In
      contrast, neither DHT nor R1881 had any effect on the oxidative stress in DU145
      cells. The mitochondrial activity in LNCaP cells, as measured by MTT reduction,
      was significantly elevated above the levels of the untreated controls by DHT (0.1
      1000 nM) and R1881 (0.05-1 nM) (P < .001 in both). Oxygen consumption and
      catalase activity were increased in LNCaP cells in the presence of 1 nM R1881 by
      60% and 40%, respectively, over the values in the untreated control cells (P <
      .03 and P < .01, respectively). The same concentration of R1881 resulted in a
      decrease in intracellular glutathione concentrations and an increase in gamma
      glutamyl transpeptidase activity in LNCaP cells. Treatment with the oxidizing
      agents H2O2 and menadione produced an increase in gamma-glutamyl transpeptidase
      activity in LNCaP cells, whereas treatment with the antioxidant compound ascorbic
      acid (100 mM) reduced the oxidative stress produced in LNCaP cells by 1 nM R1881
      and completely blocked the gamma-glutamyl transpeptidase activity. CONCLUSIONS:
      Physiologic levels of androgens are capable of increasing oxidative stress in
      androgen-responsive LNCaP prostate carcinoma cells. The evidence suggests that
      this result is due in part to increased mitochondrial activity. Androgens also
      alter intracellular glutathione levels and the activity of certain detoxification
      enzymes, such as gamma-glutamyl transpeptidase, that are important for
      maintenance of the cellular prooxidant-antioxidant balance.

PMID- 8978406
TI  - Lung cancer risk from residential radon: meta-analysis of eight epidemiologic
      studies.
AB  - BACKGROUND: Studies of underground miners exposed to radioactive radon and its
      decay products have found that exposure increases risk of lung cancer.
      Consequently, when radon was found to accumulate in houses, there was concern
      about the public health impact from exposure to a known carcinogen. Estimates on
      the basis of studies of underground miners suggest that indoor radon may account
      for 6000-36,000 lung cancer deaths each year in the United States. Because of
      differences between working in underground mines and living in houses, estimates
      are subject to major uncertainties. Numerous case-control studies were launched
      to assess directly the lung cancer risk from indoor radon. Some studies report
      positive or weakly positive findings, while others report no increased risk.
      Thus, the potential hazard from indoor radon remains answered only indirectly
      through miner studies, experimental animal studies, and cellular studies.
      PURPOSE: To provide more information on the risk of lung cancer from indoor
      radon, we conducted a meta-analysis of all case-control studies that included at
      least 200 case subjects each and that used long-term indoor radon measurements.
      METHODS: Eight studies were available and included a total of 4263 lung cancer
      case subjects and 6612 control subjects. From the published results of each
      study, confounder-adjusted relative risk (RR) estimates and 95% confidence
      intervals (CIs) for categories of radon concentration were obtained, and weighted
      linear regression analyses were performed. RESULTS: The combined trend in the RR
      was significantly different from zero (two-sided P = .03), and an estimated RR of
      1.14 (95% CI = 1.0-1.3) at 150 Bq/m3 was found. An influence analysis indicated
      that no single study dominated the combined results. The exposure-response trend
      was similar to model-based extrapolations from miners and to RRs computed
      directly from miners with low cumulative exposures. However, there were
      significant differences in the study-specific estimates of the exposure response
      (two-sided P < .001), which were not explained by study differences in percent of
      the defined exposure interval covered by radon measurements, mean number of
      residences per subject, and other factors. CONCLUSIONS: Meta-analyses are
      valuable for identifying differences among studies and for summarizing results,
      but they should be interpreted cautiously when expected RRs are low as with
      indoor radon exposure, when there is study heterogeneity and where there is the
      potential for confounding and exposure misclassification. Nonetheless, the
      results of this meta-analysis suggest that the risk from indoor radon is not
      likely to be markedly greater than that predicted from miners and indicate that
      the negative exposure response reported in some ecologic studies is likely due to
      model misspecification or uncontrolled confounding and can be rejected.
      IMPLICATIONS: Until ongoing case-control studies of indoor radon are completed
      and the data are pooled and analyzed, the studies of underground miners remain
      the best source of data to use to assess risk from indoor radon. This meta
      analysis provides support for their general validity.

PMID- 8978407
TI  - Assessing changes in the impact of cancer on population survival without
      considering cause of death.
AB  - BACKGROUND: We have previously argued against the calculation of cancer-specific
      death rates as philosophically undefined and biased. Deaths attributed to cancer
      during a particular year occur in patients diagnosed during an unknown
      distribution of past times, so cancer-specific death rates cannot be used to
      assess changes in the impact of cancer on survival of the population at specific
      periods of diagnosis. PURPOSE: Our goal was to develop and analyze three measures
      of the impact of cancer on population survival that do not use the attributed
      cause of death: 1) the age-adjusted proportion of the population diagnosed with
      cancer in a particular year and projected to be dead of any cause by a particular
      age; 2) the same measure corrected for population mortality; and 3) the expected
      years of life lost to a 20-year-old individual because of the possibility of a
      diagnosis of cancer. METHODS: Data on all adults diagnosed with any cancer during
      the period from January 1973 through December 1990 were obtained from the
      Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer
      Institute. The measures were calculated separately for various combined sex and
      race groups. Three 2-year diagnosis periods spaced 5 years apart were considered:
      1975-1976, 1980-1981, and 1985-1986. A statistical model was used to extrapolate
      survival beyond observation; the same model was used for patients diagnosed in
      the three time periods to minimize the effect of possible model misspecification
      on changes. RESULTS: Cancer incidence increased for three of the four sex-race
      groups; age-adjusted changes from 1975 through 1976 to 1985 through 1986 were
      +11.5% for white men, +6.9% for white women, +15.1% for black men, and -9.2% for
      black women. Human immunodeficiency virus (HIV)-related cancers were responsible
      for an increased cancer incidence at early ages in white men in the latest time
      period studied. There was a decrease in the incidence of gynecologic cancers at
      early ages; the decrease was greater among black women (-55.1%) than among white
      women (-39.3%). Age- and incidence-adjusted 5-year survival increased by 17.9%
      for white men, 2.3% for white women, and 7.4% for black men and decreased by
      14.1% for black women. When the data from 1985 through 1986 were compared with
      those from 1975 through 1976, the expected number of years lost to a 20-year-old
      individual because of cancer changed as follows for the various sex-race groups:
      +1.4% for white men (-4.0% if HIV-related cancers were not included in the
      calculation), +2.1% for white women, +12.2% for black men, and +8.8% for black
      women. CONCLUSIONS: For white men and women, there has been an increase in both
      the incidence of and survival following the diagnosis of cancer; the two effects
      nearly cancel in our measures. The experience of black men and women has worsened
      because of increasing incidence or decreased survival.

PMID- 8978408
TI  - p53 abnormalities in primary prostate cancer: single-strand conformation
      polymorphism analysis of complementary DNA in comparison with genomic DNA. The
      Cooperative Prostate Network.
AB  - BACKGROUND: The reported frequency of mutation of the p53 tumor suppressor gene
      (also known as TP53) in human carcinomas of the prostate has varied widely,
      ranging from 3% to 42%. This variability may be a consequence of tumor
      heterogeneity and/or the use of different methods of analysis. Since p53 mutation
      has been associated with clinical outcome for a number of cancer types,
      determination of its true frequency in primary carcinomas of the prostate is
      important. PURPOSE: The principal aims of this study were as follows: 1) to
      validate the utility of detecting p53 gene mutations by means of polymerase chain
      reaction-single-strand conformation polymorphism (PCR-SSCP) analysis of
      complementary DNA (cDNA) (synthesized from prostate tissue RNA and 2) to study
      the concordance of RNA- and DNA-based PCR-SSCP assays in detecting p53 mutations
      in individual tumor fragments. METHODS: RNA and genomic DNA were isolated by
      means of standard techniques from specimens of 19 carcinomas of the prostate,
      selected on the basis of p53 data obtained in a previous analysis of cDNA
      (indicating that 14 were mutant and five were wild-type). RNA was converted into
      cDNA by means of reverse transcription (RT); the cDNA was then amplified by means
      of nonisotopic (i.e., nonradioactive) PCR, and the PCR products were subjected to
      SSCP analysis in polyacrylamide gels (RT-PCR-SSCP analysis). Genomic DNA was
      examined by means of SSCP analysis of isotopically labeled (32PO4) PCR products
      (DNA-PCR-SSCP analysis). In both approaches, the protein coding region of the p53
      gene was divided into multiple, smaller fragments for study. PCR products
      exhibiting abnormal migration in SSCP gels were subjected to direct nucleotide
      sequencing or to cloning and sequencing of multiple clones. RESULTS: RT-PCR-SSCP
      and DNA-PCR-SSCP identified p53 gene abnormalities in 15 of the 19 selected
      carcinomas, including one previously reported to be wild-type for p53. Overall,
      PCR-SSCP analysis identified 18 p53 fragments with abnormalities; three
      carcinomas showed two abnormalities each. Six (33%) of the 18 abnormalities were
      detected by both RT-PCR-SSCP and DNA-PCR-SSCP, 10 (56%) were detected by RT-PCR
      SSCP alone, and two (11%) were detected by DNA-PCR-SSCP alone. The 18
      abnormalities were caused by 20 changes in the sequence of the p53 gene; in one
      carcinoma, double mutations in two individual p53 exons were identified.
      CONCLUSIONS AND IMPLICATIONS: PCR-SSCP analysis of both RNA and DNA allows the
      detection of more mutations than the analysis of either alone. Some primary
      carcinomas of the prostate contain more than one altered p53 gene, consistent
      with the possibility of intratumoral heterogeneity of mutation of this gene. For
      comprehensive analysis of p53 mutations in carcinomas of the prostate, and
      perhaps in other tumor tissues, SSCP analysis of cDNA should be used in
      combination with SSCP analysis of genomic DNA.

PMID- 8978409
TI  - Intrauterine environment and breast cancer risk in women: a population-based
      study.
AB  - BACKGROUND: The established risk factors for female breast cancer, including
      nulliparity, age at first birth, age at menarche, and age at menopause, do not
      adequately explain the occurrence pattern of this cancer. Therefore, additional
      factors need to be considered to advance our understanding of the causes of
      breast cancer. Evidence obtained from animals and humans indicates that the
      perinatal period may be particularly important. Our earlier studies, based on a
      subsample of the present investigation, suggested that factors thought to be
      positively associated with estrogen levels during pregnancy are positively
      associated with breast cancer risk. However, the associated confidence intervals
      (CIs) were generally wide, indicating considerable variability in the data.
      PURPOSE: We studied a large number of incident breast cancer case patients and
      evaluated several perinatal variables in relation to breast cancer risk. These
      variables included some not previously studied, such as gestational age and
      neonatal jaundice. We also investigated twin membership as a predictor variable
      and death from breast cancer, in addition to occurrence of breast cancer, as an
      alternative outcome variable. METHODS: Birth records for all deliveries at five
      different hospitals in Sweden during the period from 1874 through 1961 were used
      to define a large cohort of women. Incident case patients with breast cancer in
      this cohort were ascertained through the National Cancer Registry or the Uppsala
      Regional Cancer Registry from 1958 through 1994. In a case-control study nested
      in the cohort, we abstracted data from birth records on 1068 women with incident
      breast cancer and on 2727 control subjects individually matched to the case
      patients on date of birth. We modeled the data through conditional logistic
      regression. All P values were derived from two-sided statistical tests. RESULTS:
      We found a markedly reduced risk for breast cancer in women whose mothers had
      pregnancy toxemia (odds ratio [OR] = 0.41; 95% CI = 0.22-0.79) and an excess risk
      on women who had neonatal jaundice (OR = 2.16; 95% CI = 1.27-3.67) or who were
      born before 33 weeks of gestation (OR = 3.96; 95% CI = 1.45-10.81). Compared with
      the risk for breast cancer in the singleton, the risk for breast cancer in
      dizygotic twins was increased, although this increase was not statistically
      significant (OR = 1.72; 95% CI = 0.92-3.20). There was no evidence in these data
      for a statistically significant or substantial association of breast cancer risk
      with birth size indicators (i.e., weight and length at birth and placental
      weight). CONCLUSION AND IMPLICATIONS: Because pregnancy toxemia is associated
      with low levels of estrogens and neonatal jaundice, severe prematurity, and
      dizygotic twins with high levels of estrogens, our findings suggest that
      estrogens and other hormonal factors, known to influence breast cancer risk in
      the adult, may also play a critical role during the intrauterine period.

PMID- 8978410
TI  - Comparison of risk factors for ductal carcinoma in situ and invasive breast
      cancer.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) accounts for approximately 12% of
      newly diagnosed breast cancers. Knowledge of the factors that predict who will be
      diagnosed with DCIS is very limited. PURPOSE: The goal of this study was to
      determine risk factors associated with DCIS and whether these risk factors are
      similar to those associated with invasive breast cancer. METHODS: We conducted a
      cross-sectional study of 39,542 women aged 30 years and older who underwent a
      screening mammographic examination at the University of California San Francisco
      Mobile Mammography Screening Program from April 1985 through September 1995. A
      breast cancer risk profile and clinical history were obtained for each woman.
      Follow-up after abnormal mammography was performed to determine the presence of
      DCIS or invasive breast cancer by contacting the women's physicians and by
      linkage to the regional Surveillance, Epidemiology, and End Results cancer
      registry. Multivariate analysis was performed by the use of polytomous logistic
      regression. Two-sided statistical tests were used to determine P values. RESULTS:
      Among women aged 30-49 years, a family history of breast cancer (i.e., at least
      one affected first degree relative) was associated with an increased risk of DCIS
      (Odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.1-4.9) and body mass
      index greater than or equal to 25 kg/m2 was associated with a decreased risk of
      DCIS (OR = 0.4, 95% CI = 0.2 to 0.9). For each of these factors, there was a
      trend in the same direction bordering on statistical significance for invasive
      cancer (ORs = 1.7 [95% CI = 0.9-3.4] and 0.6 [95% CI = 0.3-1.1], respectively).
      Report of a palpable mass was associated with an increased risk of invasive
      cancer among women aged 30-49 years (OR = 12.0; 95% CI = 7.1-20.0); there was a
      trend in the same direction for DCIS (OR = 2.0; 95% CI = 0.8-5.1), but the
      association was much stronger for invasive disease than for DCIS (OR = 6.0; 95%
      CI = 2.1-18.0; P = .001). Among women aged 50 years and older, family history of
      breast cancer and nulliparity or age at birth of first child of 30 years or older
      increased the risk of both DCIS (ORs = 2.2 [95% CI = 1.0-4.2] and 2.3 [95% CI =
      1.3-3.8], respectively) and invasive breast cancer (ORs = 1.5 [95% CI = 1.0-2.2]
      and 1.6 [95% CI = 1.2-2.1], respectively). Report of a palpable mass was not
      associated with an increased risk of DCIS among women 50 years and older, but it
      was strongly associated with an increased risk of invasive cancer (OR = 9.3; 95%
      CI = 6.0-14.0). Increasing age was associated with an increased risk of both DCIS
      and invasive cancer among women aged 30-49 years, but the association was
      stronger for invasive disease; a trend in the same direction bordering on
      statistical significance was observed for women aged 50 years and older.
      CONCLUSION: Risk factors for DCIS are similar to those for invasive breast
      cancer. IMPLICATIONS: More research is needed to better understand the malignant
      potential of DCIS lesions and factors that predict which lesions will become
      invasive breast cancer if left untreated.

PMID- 8978411
TI  - Hereditary retinoblastoma, lipoma, and second primary cancers.

PMID- 8978412
TI  - Re: Severe neurotoxicity in vinorelbine-paclitaxel combinations.

PMID- 8978413
TI  - Re: Stage IIIA category of non-small-cell lung cancer: a new proposal.

PMID- 8978414
TI  - Re: Ethnic differences in estrogen metabolism in healthy women.

PMID- 8978415
TI  - Thyroid cancer in the Pacific.

PMID- 8978416
TI  - Paclitaxel-induced pancreatitis: a case report.

PMID- 8978417
TI  - Re: B-cell non-Hodgkin's lymphoma: evidence for the t(14;18) translocation in all
      hematopoietic cell lineages.

PMID- 8978418
TI  - Re: Smoking and colorectal cancer: a 20-year follow-up study of Swedish
      construction workers.

PMID- 8978419
TI  - Semen of smokers and cervical cancer risk.

PMID- 8978420
TI  - Advances in Ultrafast Computed Tomography: 1996. An International Symposium on
      Electron Beam Tomography. Lake Buena Vista, Florida, October 4-6, 1996.
      Abstracts.

PMID- 8978422
TI  - 7th International Conference on Chronopharmacology and Chronotherapeutics.
      Heidelberg, Germany, September 10-14, 1996. Abstracts.

PMID- 8978421
TI  - 19th Annual San Antonio Breast Cancer Symposium. December 11-14, 1996. Abstracts.

PMID- 8978423
TI  - Annual meeting of the American Academy for Cerebral Palsy and Developmental
      Medicine, 1993. Abstracts.

PMID- 8978424
TI  - British Diabetic Association's Education and Care Section Annual Conference 18-20
      September 1996 and Medical and Scientific Section Autumn Meeting 19-20 September
      1996, Exeter University. Abstracts.

PMID- 8978425
TI  - VII World Meeting on Impotence. San Francisco, California, 3-7 November 1996.
      Abstracts.

PMID- 8978426
TI  - The Physiological Society proceedings of the scientific meeting held at
      University College London, 16-18 April 1996. Abstracts.

PMID- 8978427
TI  - Catalogue of contents and author index. 1990-1995.

PMID- 8978429
TI  - [International Journal of Food Research and Technology].

PMID- 8978428
TI  - CHOQUE 96: 2nd Brazilian Shock Congress, SALT 7: 7th International Conference on
      Hypertonic Resuscitation. Sao Paulo, Brazil, 11-14 November 1996. Abstracts.

PMID- 8978430
TI  - The Academy of Aphasia 34th annual meeting. London, England, November 3, 1996.
      Abstracts.

PMID- 8978431
TI  - New advances in EEG and cognition.

PMID- 8978432
TI  - Intention as a component of the alpha-rhythm response to mental activity.
AB  - Many studies of alpha-rhythm reactivity conclude that alpha is selectively
      attenuated by attention accompanying mental activity. The topography of this
      attenuation is assumed to match the relevant functional topography of the cortex.
      But there are reports of apparent increased attention resulting in no change, or
      even enhanced alpha - the paradoxical response. It is proposed that in this case,
      alpha amplitude may be dependent on an intention component of behaviour. Some
      conflicting reports of alpha reactivity to mental processes may then be resolved.
      It is argued that the classical attention model of alpha is untenable, except for
      simple sensori-motor responses. Reasons are given to support this and the concept
      of intention as a neuropsychological variable is introduced. Evidence is
      presented for a generalisation of an oculomotor model of alpha activity proposed
      by Wertheim who demonstrated that alpha reduces during attentive, but not during
      intentive visual behaviour. The generalisation follows from reports of enhanced
      alpha in the few seconds prior to a skilled action in sport, and by
      neurophysiological evidence for a separate cortical organisation for perception
      and action. Varying proportions of attention and intention then add a dimension
      to the factors influencing alpha blocking which may explain its inconsistent
      response.

PMID- 8978433
TI  - Measurements by biphasic changes of the alpha band amplitude as indicators of
      arousal level.
AB  - The objective of this study was to develop a method of measuring arousal level by
      examining the change rates with activation of the alpha band amplitude using the
      concept of the inverted U-shaped pattern of transition of this amplitude. We
      investigated change rates by inspecting the electroencephalogram, and we
      evaluated their correlations with a criterion index of the arousal level (a
      reaction time measure), and other relevant basic parameters in 14 normal
      volunteers. In order to confirm that alpha band amplitude change followed an
      inverted U-shaped curve, we examined the transition of that index in a resting
      and-relaxing condition. In the third session, the change rates upon stimulation
      and after resting had positive and negative correlations, respectively, with the
      reaction time measure, verifying that they are 'negative' and 'positive' arousal
      level indices. Further examinations were conducted for the third session. The
      change rates upon stimulation and after resting had negative correlations with
      each other. Neither of them had a significant correlation with the alpha band
      amplitude. Neither alpha band frequency, alpha band amplitude, or theta band
      amplitude, all of which are regarded as indices for intra-subject arousal level
      transition, had any significant correlation with the reaction time measure. These
      results revealed that the change rates of the alpha band amplitude are better
      indices for inter-individual arousal level variation than other conventional
      indices.

PMID- 8978434
TI  - Event-related synchronization (ERS) in the alpha band--an electrophysiological
      correlate of cortical idling: a review.
AB  - EEG desynchronization is a reliable correlate of excited neural structures of
      activated cortical areas. EEG synchronization within the alpha band may be an
      electrophysiological correlate of deactivated cortical areas. Such areas are not
      processing sensory information or motor output and can be considered to be in an
      idling state. One example of such an idling cortical area is the enhancement of
      mu rhythms in the primary hand area during visual processing or during foot
      movement. In both circumstances, the neurons in the hand area are not needed for
      visual processing or preparation for foot movement. As a result of this, an
      enhanced hand area mu rhythm can be observed.

PMID- 8978435
TI  - Event-related desynchronization (ERD) and the Dm effect: does alpha
      desynchronization during encoding predict later recall performance?
AB  - Based on previous research which has shown that event-related desynchronization
      (ERD) in the lower and upper alpha band reflects attentional and semantic
      processing respectively, the present study examines the hypothesis whether event
      related shifts in the two alpha bands are capable of predicting later recall
      performance. In an incidental memory paradigm, subjects first had to judge the
      category membership for a set of 96 words. Later, without prior warning, subjects
      were asked to recall the words. The results show that for good performers, the
      extent of ERD in the lower alpha band during the semantic encoding for words is
      significantly larger for remembered as compared to not remembered words, whereas
      for bad performers the ERD in the upper alpha band is significantly more
      pronounced. This type of Dm effect is particularly strong over parietal recording
      sites in both hemispheres. In referring to the proposed interpretation of the
      lower and upper alpha band, the present findings seem to indicate that in
      contrast to good performers, bad performers are less attentive or alert during
      encoding. Event-related potentials (ERPs) also yielded significant Dm effects at
      parietal recording sites.

PMID- 8978436
TI  - Memory processes, brain oscillations and EEG synchronization.
AB  - This article tries to integrate results in memory research from divergent
      disciplines such as cognitive psychology, neuroanatomy, and neurophysiology. The
      integrating link is seen in more recent findings that provide strong arguments
      for the assumption that oscillations are a basic form of communication between
      cortical cell assemblies. It is assumed that synchronous oscillations of large
      cell assemblies--termed type 1 synchronization--reflect a resting state or
      possibly even a state of functional inhibition. On the other hand, during mental
      activity, when different neuronal networks may start to oscillate with different
      frequencies, each network may still oscillate synchronously (this is termed type
      2 synchronization), but as a consequence, the large scale type 1 oscillation
      disappears. It is argued that these different types of synchronization can be
      observed in the scalp EEG by calculating event-related power changes within
      comparatively narrow but individually adjusted frequency bands. Experimental
      findings are discussed which support the hypothesis that short-term (episodic)
      memory demands lead to a synchronization (increase in band power) in the theta
      band, whereas long-term (semantic) memory demands lead to a task-specific
      desynchronization (decrease or suppression of power) in the upper alpha band.
      Based on these and other findings, a new memory model is proposed that is
      described on three levels: cognitive, anatomical and neurophysiological. It is
      suggested that short-term (episodic) memory processes are reflected by
      oscillations in an anterior limbic system, whereas long-term (semantic) memory
      processes are reflected by oscillations in a posterior-thalamic system.
      Oscillations in these frequency bands possibly provide the basis for encoding,
      accessing, and retrieving cortical codes that are stored in the form of widely
      distributed but intensely interconnected cell assemblies.

PMID- 8978437
TI  - Gamma-band responses in the brain: a short review of psychophysiological
      correlates and functional significance.
AB  - The present study shows that gamma-band (40 Hz) activities exist in a number of
      brain structures of different species, with seemingly different
      functional/behavioral correlates. This rhythm has also different dynamics in
      various structures and under different experimental conditions: it exists
      spontaneously and/or can be evoked, induced or emitted with different latencies
      and relations to sensory-cognitive events. Recent measurements of gamma-band
      activity at the cellular level stress high level functional correlates such as
      binding of features. In contrast, field potential measurements in both humans and
      animals demonstrate that gamma-band responses may have multifold functions both
      in 'obligatory' sensory and in cognitive processing. With respect to the
      generators of gamma activity, experimental data hint at the existence of a
      distributed gamma system in the brain. Furthermore, an interpretation of gamma
      rhythms as universal functional building blocks is suggested.

PMID- 8978438
TI  - Frontal gamma-band enhancement during multistable visual perception.
AB  - The aim of our study was to find out whether an increase in the gamma band may be
      related to the reversal phase during viewing of an ambiguous pattern. The present
      study describes the significant gamma band (30-50 Hz) activity increase in EEG
      during states of perceptual switching (reversal state). In our experiments the
      multistability was induced with an ambiguous stimulus pattern, known as
      stroboscopic alternative motion (SAM). The investigations carried out in 11
      subjects included a measuring strategy with three different experimental
      conditions: (1) recording of spontaneous EEG as baseline; (2) recording of the
      EEG during naive observation of the ambiguous pattern; (3) recording of EEG
      during active observation of SAM. The results indicate that the multistable
      perception is one of the multifold cognitive processes giving rise to 40 Hz
      enhancement in the entire cortex. The most significant 40 Hz enhancements were
      measured in frontal areas and can reach increases of 40 to 50% in states of naive
      and active observations of SAM, respectively, in comparison to spontaneous EEG
      recordings. The results indicate that the increase of frontal gamma band is
      related to the destabilization of the perceptual system when viewing multistable
      patterns.

PMID- 8978439
TI  - Electrophysiological analysis of the registration, storage and retrieval of
      information in delayed matching from samples.
AB  - Brain processes of registration, storage in working memory and retrieval of
      different kinds of information were studied by analysis of EEG and ERP activity
      recorded during two delayed matches from sample tasks: (1) matching the digits in
      two series of six numbers, and (2) matching the sums of the same two series of
      six numbers. each trial was composed of six intervals continuing six equally
      spaced visual stimuli: (1) control--observing a series of six fixation points,
      P1, on a computer monitor; (2) priming--viewing a series, S1, of six numbers; (3)
      delay--observing a second series of six fixation points, P2; (4) matching-
      viewing a second series, S2, of six numbers; (5) response selection--selecting
      the left button to press if S1 contained all the items in S2 or the right button
      if any item appeared only in S2, while observing six fixation points; (6)
      feedback--six color coded fixation points indicate correct or error. Each
      interval was 4 s in duration and 20 trials were presented in each task. During
      each interval the visual field flickered at a tracer frequency of 1.5/s, whether
      numbers or fixation points were on the monitor screen. Very narrow band power
      spectra (VNB), ERPs elicited by presentation of S1 or S2 information items, and
      non-contingent probes (NCP) elicited by presentation of fixation points were used
      to trace the processing of information by neural populations activated by the
      visual stimulation. Global field power maxima identified latencies at which
      functional landscapes were analyzed. VNB, ERP, NCP and landscape differences were
      found between digits and sums. However, though these differences were highly
      significant within each subject (p < 0.001), no consistency was found across
      individuals for the electrophysiological changes during the tasks. This suggests
      that utilization of brain resources in cognition varies greatly with individual
      cognitive styles and strategies.

PMID- 8978440
TI  - Approaches to verbal, visual and musical creativity by EEG coherence analysis.
AB  - Our approach to coherence analysis of the on-going EEG yields data on the
      cooperation between all possible electrode sites of the 10/20 system. This
      procedure compares epochs during mental activity with epochs of EEG at rest and
      takes into account only significant differences which are represented as lines
      between the respective electrodes on maps of the brain surface. The patterns thus
      obtained reflect the temporal average of the changes of the overall coherence
      pattern caused by any mental task. They are interpreted as reflecting
      differential attention required for the achievement of the mental task in
      question. Acts of creative thinking, be it verbally, visually or musically, are
      characterized by more coherence increases between occipital and frontopolar
      electrode sites than any other mental tasks. The results are interpreted by a
      stronger involvement of long cortico-cortical fibre systems in creative tasks.

PMID- 8978441
TI  - EEG delta activity: an indicator of attention to internal processing during
      performance of mental tasks.
AB  - In previous papers we proposed that an increase in delta EEG activity during
      mental tasks might be related to an increase in subjects' attention to internal
      processing. In this paper we have made a narrow band analysis to detect those EEG
      frequencies that change selectively during the performance of a mental task that
      requires attention to internal processing. Two different experiments were
      performed: (1) a difficult mental calculation task and a control stimulus with
      the same physical characteristics as the arithmetical symbols were presented in
      random order; (2) the Sternberg paradigm for the analysis of short term memory
      using a memory set of 5 or 3 digits was also presented in random order.
      Referential recordings to linked ears were obtained in all leads of the 10/20
      system. In the first experiment, the increase of power from 1.56 to 5.46 Hz was
      observed only during the performance of the task and not during the control
      condition. In the Sternberg paradigm, the increase of power from 1.56 to 3.90 Hz
      was greater during the difficult than during the easy condition. These results
      support our hypothesis that an increase in delta activity may be related to
      attention to internal processing during the performance of a mental task.

PMID- 8978442
TI  - Working-memory load and dimensional complexity of the EEG.
AB  - This investigation shows that a working-memory load induced by a memory scanning
      task has an effect on nonlinear descriptors of the EEG dynamics. The effect was
      locally specific above the fronto-temporal (right) cortex and it may be described
      as a reduction in the dimensional complexity of cortical brain activity. The
      meaning of the effects seems to differ from that of EEG spectral power, which
      varied with time during the experiment and not with changes in the working-memory
      load conditions. Behaviorally controlled over- and underload led to increased
      variance of the dimensional complexity, thus indicating that dimensional
      complexity correlates more closely with actual performance than with more general
      descriptions of brain states. Habitual response speed had an effect at the
      parietal lead, thus indicating that fast responders reduced their dimensional
      complexity as the task demand increased. In contrast, the slower responders
      showed no such definite trend.

PMID- 8978443
TI  - The use of MRI in monitoring the treatment of multiple sclerosis.

PMID- 8978444
TI  - Magnetic resonance in monitoring the natural history of multiple sclerosis and
      the effects of treatment.
AB  - In this review the main contributions of magnetic resonance (MR) techniques in
      the monitoring of multiple sclerosis (MS) course, both natural or modified by
      treatments, are presented. MR measures well correlate with short-term disease
      evolution and therefore their use is appropriate as primary end-points in
      preliminary clinical trials evaluating the effects of new treatments. In
      contrast, the correlation between MR measures and long-term clinical evolution in
      clinically definite MS is less clear, thus indicating that such measures can be
      used at present only as a secondary end-point in large scale definitive trials.
      The results coming from the clinical application of newer MR techniques with
      higher pathological specificity are also presented and their possible future
      roles in monitoring treatment aimed at preventing development of disability in MS
      are discussed.

PMID- 8978445
TI  - Progressive multifocal leucoencephalopathy.
AB  - Progressive multifocal leucoencephalopathy (PML) is a rarely occurring
      demyelinating disease of the central nervous system caused by a neurotropic
      papovavirus named JC virus (JCV). The most frequently affected affected regions
      are the cerebral hemispheres, especially the parietooccipital region, followed by
      the cerebellum and brain stem. The disease occurs predominantly in individuals
      with an immunocompromised state and impaired cellular mediated immunity (CMI) due
      to other underlying illness. More extensive use of irradiation and
      immunosuppressive therapy in relation to increased transplantational activities
      as well as treatment of autoimmune diseases and malignancies, in addition to the
      appearance of the acquired immunodeficiency syndrome (AIDS) as a consequence of
      infection with the human immunodeficiency virus (HIV), has caused a considerable
      increase in the occurrence of PML. The course of the disease is still most often
      rapidly progressive and fatal, but several cases with prolonged survival and even
      remission have been reported, and various antiviral treatments have been tried.
      The only drug that until now has shown favourable results is cytosine
      arabinoside. In HIV-infected PML-patients immunomodulation with AZT/zidovudine
      may alleviate the course and improve the prognosis in some patients. Suspicion of
      PML should lead to an extensive immunological investigation before considering of
      brain biopsy, which is still the only specific test. On the basis of the
      increased frequency of PML in relation to HIV-infection, it is likely that our
      knowledge of the pathogenetic aspects will increase, which, hopefully, may lead
      to an effective therapeutic strategy.

PMID- 8978446
TI  - Time of hospital presentation after stroke. A multicenter study in north-east
      Italy. Italian SINV (Societa Interdisciplinare Neurovascolare) Study group.
AB  - Given the current orientation towards the early treatment of stroke, this
      multicenter study was carried out in North-east Italy in order to examine the
      times between stroke onset and hospital admission, and the possible factors
      leading to a lengthening of such times. An analysis was made of 348 patients,
      79.8% of whom had experienced an ischemic cerebral infarct. Arrival times were
      not significantly modified by the distance from hospital, age, family
      cohabitation, socio-cultural level, population density or the geographical
      location of the Center. Sixty percent of the ischemic stroke cases arrived at the
      Emergency Department within three hours, and 80% within six hours; the
      hemorrhagic cases arrived earlier, 100% of them by the tenth hour. The duration
      of stay in the Emergency Department did not vary in relation to the severity or
      type of stroke. Greater severity, a reduced level of awareness and daytime onset
      led to a moderately significant reduction on presentation times. In conclusion,
      the majority of patients arrived sufficiently quickly to be treated within the
      "therapeutic window"; nevertheless, an information campaign may be useful in
      accelerating the hospital presentation of the albeit limited number of cases who
      arrive late.

PMID- 8978448
TI  - Cerebral venous thrombosis in young adults. Experience in a stroke unit, 1988
      1994.
AB  - We report a series of nine patients younger than 45 years with angiographically
      documented cerebral venous thrombosis, consecutively referred to our Stroke Unit
      from 1988 to 1994. Two of them were men and seven were women. Eight patients
      initially complained of headache, often associated with other symptoms of
      increased intracranial pressure. Seven patients had focal motor deficits and four
      suffered from epileptic seizures. None of the patients died. Only one patient
      remained severely disabled, whereas the others recovered self-sufficiency within
      two months. The use of oral contraceptives was closely associated with the
      occurrence of venous thrombosis in the women. Cerebral venous thrombosis is to be
      kept in mind in the differential diagnosis of stroke in the young.

PMID- 8978447
TI  - Tardive dystonia. Prevalence, risk factors and clinical features.
AB  - In order to replicate the results of our previous study of tardive dystonia (TDt)
      and to enlarge the studied sample, we examined 154 consecutive psychiatric in
      patients who had been exposed to neuroleptic drugs for a cumulative period of at
      least three months. The present study provides further data supporting a
      distinction between TDt and tardive dyskinesia (TDk). The patients with TDt tend
      to be younger, male, less exposed to neuroleptic drugs, and to have a more severe
      movement disorder. TDt appears to be the most frequent form of secondary
      dystonia, and there is evidence that its prevalence has so far been
      underestimated.

PMID- 8978449
TI  - Changes in sleep spindle activity of subject with chronic somatosensitive and
      sensorial deficits. Preliminary results.
AB  - We investigated the effects of the somatosensitive and sensory afferent inputs on
      the thalamic generators of sleep spindles (SS) in adult subjects affected by
      posterior funiculi lesions (five subjects), deafness (four subjects) or blindness
      (four subjects). The density, duration and frequency of SS, as well as the index
      of spindling, were analyzed during stage 2 NREM. The results show that the
      subjects with somatosensitive and sensorial lesions spent much more time on SS
      activity than the control group (eight subjects), and had a significantly
      increased density (< .0001), duration (< .0005) and index of spindling (< .0001).
      On the other hand, the frequency of spindling was little modified (< .05).
      Moreover, among the three groups of patients, those with somatosensitive deficits
      showed the greatest SS activity. In conclusion, our results suggest that the
      thalamic generators of SS are markedly modulated by peripheral inputs in man.

PMID- 8978450
TI  - Efficacy and safety of topiramate in refractory epilepsy: a long-term prospective
      trial.
AB  - The effects of topiramate in 15 patients with drug refractory epilepsy or Lennox
      Gastaut syndrome were assessed in an open, add-on prospective study. After a
      follow-up of 14-21 months, six patients are still on topiramate (mean dosage 583
      mg/day, range 400-800 mg/day), and nine have discontinued treatment because of
      adverse events (n = 6), inefficacy (n = 2) or poor compliance (n = 1). Nine
      patients (69%) continued to have > or = 50% reduction in seizure frequency during
      the last two months of treatment, and one has been seizure-free for the last 19
      months. The most common adverse events were somnolence, weight loss, mental
      slowing, fatigue, ataxia and irritability. Most of these events were reversible,
      but withdrawal of treatment was required in six cases as a result of ataxia (two
      patients), somnolence, metabolic acidosis, irritability or psychotic symptoms
      (one patient each). It is concluded that topiramate is a valuable agent for long
      term management of refractory epilepsy.

PMID- 8978451
TI  - Bilateral simultaneous cerebellar infarction in the medial branches of the
      posterior inferior cerebellar artery territories.
AB  - We present an unusual case of simultaneous bilateral cerebellar infarction in the
      territory of the medial and intermediate branches of the posterior inferior
      cerebellar arteries (mPICA). The patient, a 57-yr-old woman, had no risk factors
      for cerebrovascular disease but a long-standing hypertension. Pathogenetic
      hypotheses of this unusual ischemic site of lesion may be referred to: A) two
      PICAs arising from an occluded basilar artery; B) both medial branches arising
      from the same PICA on one side; C) a haemodynamic mechanism with hypoperfusion in
      the most peripheral branches of the arteries; D) a double, simultaneous embolic
      stroke in mPICAs territory. Based on clinical course, supraortic duplex-scan,
      echocardiography, MRI, angioMRI and CT scans, and digital subtraction
      angiography, none of these hypotheses could be clearly associated with the
      pathogenesis of the lesion. Nevertheless, we propose that an anomalous common
      mPICA for both cerebellar territories should represent the necessary condition
      for the ischemic insult and, simultaneously, other factors should intervene as
      possible determining events.

PMID- 8978452
TI  - Human heart rate variability and sleep stages.
AB  - With the aim of better understanding the dynamic changes in sympatho-vagal tone
      occurring during the night, human heart rate variability (HRV) during the various
      sleep stages was evaluated by means of autoregressive spectral analysis. Each
      recording consisted of an electroencephalogram, an electrooculogram, and
      electromyogram, and electrocardiogram, and a spirometry trace. All of the data
      were sampled and stored in digital form. Sleep was analysed visually, but HRV was
      analysed off-line by means of original software using Burg's algorithm to
      calculate the LF/HF ratio (LF: 0.04-0.12 Hz; HF: 0.15-0.35 Hz) for each sleep
      stage. Seven healthy subjects (four males; mean age 35 years) were enrolled in
      the study. Our findings show a progressive and significant reduction in the LF/HF
      ratio through sleep stages S1-S4, as a result of an increase in the HF component;
      this indicates the prevalence of parasympathetic activity during slow-wave sleep.
      During wakefulness, S1 and REM, the LF/HF values were similar and close to 1.

PMID- 8978453
TI  - Lamotrigine and pregnancy.

PMID- 8978454
TI  - Increased expression of V beta 1.2 T cells in the cerebrospinal fluid of patients
      with multiple sclerosis.

PMID- 8978455
TI  - Hybrid nucleoprotein particles containing a subset of male and female histone
      variants form during male pronucleus formation in sea urchins.
AB  - To determine the changes in chromatin organization during male pronucleus
      remodeling, we have compared the composition of nucleoprotein particles (NP-ps)
      resulting from digestion with endogenous nuclease (ENase) and with micrococcal
      nuclease (MNase). Whole nuclei were isolated from sea urchin gametes and zygotes
      containing partially decondensed (15 min postinsemination, p.i.) or a fully
      decondensed (40 min p.i.) male pronucleus and digested with nucleases. The NP-ps
      generated were analyzed in agarose gels, and their histone composition was
      determined. Sperm core histones (SpH) and cleavage stage (CS) variants were
      identified by Western immunoblots revealed with specific antibodies. A single NP
      ps was generated after digestion of sperm nucleus with MNase, which migrated in
      agarose gels between DNA fragments of 1.78-1.26 Kb. Sperm chromatin remained
      undigested after incubation in ENases activating buffer, indicating that these
      nuclei do not contain ENases. One type of NP-ps was obtained by digestion of
      unfertilized egg nuclei, either with ENase or MNase; the NP-ps was located in the
      region of the agarose gel corresponding to DNA fragments of 3.4-1.95 Kb
      [Imschenetzky et al. (1989): Exp Cell Res 182:436-444]. When whole nuclei from
      zygotes containing the female pronucleus and a partially remodeled male
      pronucleus were digested with ENase, a single NP-ps was generated, which migrated
      between DNA fragments of 2.5-1.9 Kb. This particle contained only CS histone
      variants. Alternatively, when these nuclei were digested with MNase, two NP-ps
      were generated; the slower migrating NP-ps (s) was located in the same position
      of the agarose gel as those resulting from ENase digestion and the faster
      migrating NP-ps (f) migrated between DNA fragments of 1.95-1.26 Kb. It was found
      that NP-ps (s) contained only CS histone variants, whereas NP-ps (f) were formed
      by a subset of SpH and by CS histone variants. When nuclei from zygotes
      containing a fully decondensed male pronucleus were digested either with ENase or
      MNase, a single type of NP-ps was observed, which migrated in the same position
      as NP-ps (s) in agarose gels. This particle contained only CS histone variants.
      On the basis of the histone compositions and on electrophoretic similarities, it
      was concluded that NP-ps (s) originated from the female pronucleus and that NP-ps
      (f) were generated from the partially remodeled male pronucleus. Consequently,
      our results indicate that at an intermediate stage of male pronucleus remodeling
      the chromatin is formed by NP-ps containing a subset of both SpH and of CS
      histone variants, whereas at final stages of male pronucleus decondensation
      chromatin organization is similar to that of the female pronucleus.

PMID- 8978456
TI  - Regulation of rat interstitial collagenase gene expression in growth cartilage
      and chondrocytes by vitamin D3, interleukin-1 beta, and okadaic acid.
AB  - The interstitial collagenase produced by the rat growth plate chondrocytes is the
      homologue of the human collagenase-3, or matrix metalloproteinase-13. This enzyme
      is responsible for the loss of collagen during hypertrophy of chondrocytes and
      for the degradation of transverse septa in long bone growth. Rachitic rats (42
      days, male Sprague-Dawley) had an 8-fold higher level of collagenase mRNA in the
      hypertrophic versus proliferative zone of growth plate cartilage. Intramuscular
      injection of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3; 1.0 micrograms/kg body
      weight) in rachitic rats increased collagenase mRNA another 1.5-fold in the
      hypertrophic zone. The regulation of collagenase gene by 1,25-(OH)2D3 and
      interleukin (IL)-1 beta in cultured proliferative chondrocytes was studied by
      means of steady-state mRNA and half-life determination of mRNA using the
      transcriptional inhibitor actinomycin D, and nuclear run-on transcription
      analyses. Treatment of cells with 1,25-(OH)2D3 (10(-6) M) and IL-1 beta (2 ng/ml)
      increased collagenase mRNA 8- and 13-fold, respectively. Additionally, the
      collagenase mRNA half-life was increased by 1,25-(OH)2D3 and IL-1 beta. In the
      presence of a protein kinase C inhibitor, staurosporine, 1,25-(OH)2 D3 induction
      of collagenase mRNA was blocked. Here the addition of phorbol 12-myrisate 13
      acetate (PMA) to activate protein kinase C increased collagenase mRNA 10-fold.
      However, in the presence of staurosporine (50 nM), PMA induction was blocked,
      whereas IL-1 beta was not. IL-1 beta is known to activate several phosphorylation
      pathways. Okadaic acid (500 nM), a protein phosphatase inhibitor, increased the
      relative collagenase mRNA abundance 10-fold. The rate of the rat collagenase gene
      transcription in nuclei was increased with 1,25-(OH)2D3, IL-1 beta and okadaic
      acid. In separate experiments, the collagenase promoter was ligated to a reporter
      plasmid and the plasmid was transfected into chondrocytes. The results showed
      that 1,25-(OH)2D3, IL-1 beta, and PMA increased reporter activity 2.5-, 2.8-, and
      3.27-fold, respectively. Thus, there are multiple nuclear and cytoplasmic
      mechanisms by which cartilage modulators regulate rat interstitial collagenase
      gene expression.

PMID- 8978457
TI  - Identification and characterization of opioid and somatostatin binding sites in
      the opossum kidney (OK) cell line and their effect on growth.
AB  - Opioids and somatostatin analogs have been implicated in the modulation of renal
      water handling, but whether their action is accomplished through central and/or
      peripheral mechanisms remains controversial. In different cell systems, on the
      other hand, opioids and somatostatin inhibit cell proliferation. In the present
      study, we have used an established cell line, derived from opossum kidney (OK)
      proximal tubules, in order to characterize opioid and somatostatin receptors and
      to investigate the action of opioids and somatostatin on tubular epithelial
      tissue. Our results show the presence of one class of opioid binding sites with
      kappa, selectivity (KD 4.6 +/- 0.9 nM, 57,250 sites/cell), whereas delta, mu, or
      other subtypes of the kappa site were absent. Somatostatin presents also a high
      affinity site on these cells (KD 24.5 nM, 330,000 sites/cell). No effect of
      either opioids or somatostatin on the activity of the NA+/Pi cotransporter was
      observed, indicating that these agents do not affect ion transport mechanisms.
      However, opioid agonists and somatostatin analogs decrease OK cell proliferation
      in a dose-dependent manner; in the same nanomolar concentration range, they
      displayed reversible specific binding for these agents. The addition of
      diprenorphine, a general opioid antagonist, reversed the effects of opioids, with
      the exception of morphine. Furthermore, morphine interacts with the somatostatin
      receptor in this cell line too, as was the case in the breast cancer T47D cell
      line. Our results indicate that in the proximal tubule opioids and somatostatin
      do not affect transport, but they might have a role in the modulation of renal
      cell proliferation either during ontogenesis or in kidney repair.

PMID- 8978458
TI  - Final checkpoint in the drug-promoted and poliovirus-promoted apoptosis is under
      post-translational control by growth factors.
AB  - The treatment of HeLa subline (HeLa-B) cells with cycloheximide or Actinomycin D
      resulted in a rapid (approximately 1.5 h and approximately 2.5 h, respectively)
      development of morphological and biochemical signs of apoptosis. The addition of
      fetal bovine serum to the cycloheximide-treated or Actinomycin D-treated cells
      suppressed the apoptotic reaction, as evidenced by the postponement of the DNA
      fragmentation for at least 9 and 5 h, respectively. A similar suppressive effect
      was observed upon the serum addition to cells undergoing abortive infection with
      poliovirus, which died of apoptosis in the absence of the serum. The serum
      appeared to exert its anti-apoptotic effect without any appreciable lag and even
      immediately blocked further progress of ongoing DNA fragmentation. The epidermal
      growth factor also suppressed, although less efficiently and more transiently,
      the apoptotic reaction promoted by the metabolic inhibitors. It is concluded that
      growth factors may affect, without modulating either transcription or
      translation, the balance of pro-apoptotic and anti-apoptotic activities at a
      final checkpoint, just preceding the irreversible effector step of apoptosis.

PMID- 8978459
TI  - Fluid shear stress induces actin polymerization in human neutrophils.
AB  - We have previously reported that a physiological range of shear stress induces
      neutrophil homotypic aggregation mediated by lymphocyte function-associated
      antigen-1 (LFA-1) and intercellular adhesion molecule-3 (ICAM-3) interactions. To
      further characterized the homotypic aggregation, actin polymerization was
      investigated in neutrophils stimulated by shear stress in comparison with formyl
      methionyl-leucyl-phenylalanine (fMLP). In fMLP-stimulated neutrophils, actin
      polymerization was localized in the pseudopods, and this reaction was not
      mediated by a cytosolic level of Ca2+. In contrast to fMLP stimulation, the actin
      polymerization induced by shear stress in a cone-plate viscometer was localized
      in cell-cell contact regions, and this polymerization required the increase of
      intracellular Ca2+. This shear stress-induced actin polymerization was not
      observed when neutrophils were pretreated with anti-LFA-1 or anti-ICAM-3
      antibody. In conclusion, LFA-1 and ICAM-3 interaction mediated by the increase of
      [Ca2+]i generated the intercellular signal in order to accumulate F-actin in the
      cell-cell contact regions.

PMID- 8978460
TI  - Nuclear membrane cholesterol can modulate nuclear nucleoside triphosphatase
      activity.
AB  - Previous work has suggested that changes in nuclear membrane cholesterol may
      induce a stimulation in nuclear nucleoside triphosphatase (NTPase) activity. The
      purpose of the present study was to directly investigate if nuclear membrane
      cholesterol can stimulate nuclear NTPase activity. The cholesterol content of
      nuclei was altered with a liposomal methodology. The cholesterol content of
      nuclei isolated from hepatic tissue was relatively low in comparison to that
      typically exhibited by other membrane fractions. Because of this, it was
      difficult to further deplete the nuclear membrane of cholesterol, but we could
      successfully increase the cholesterol content after exposure to cholesterol
      enriched liposomes. Nuclear NTPase activity was potently stimulated
      (approximately 150-200% of control) by an increase in the nuclear membrane
      cholesterol content. The Vmax of the NTPase activity in the presence of ATP or
      GTP was significantly increased after cholesterol enrichment without altering the
      affinity of the enzyme for these moieties. Mg2+ dependency of NTPase activity was
      also altered by cholesterol incorporation into the nuclear membrane. Cholesterol
      enrichment of the nuclear membrane also left the nuclei more susceptible to
      damage by salt-induced lysis than control nuclei. Our results clearly demonstrate
      that the cholesterol content of the nuclear membrane will have significant,
      direct effects on nuclear integrity and NTPase activity.

PMID- 8978461
TI  - Localization of the fructose 1,6-bisphosphatase at the nuclear periphery.
AB  - The localization of fructose 1,6-bisphosphatase (D-Fru-1,6-)2-1-phosphohydrolase,
      EC 3.1.3.11) in rat kidney and liver was determined immunohistochemically using a
      polyclonal antibody raised against the enzyme purified from pig kidney. The
      immunohistochemical analysis revealed that the bisphosphatase was preferentially
      localized in hepatocytes of the periportal region of the liver and was absent
      from the perivenous region. Fructose-1,6-bisphosphatase was also preferentially
      localized in the cortex of the kidney proximal tubules and was absent in the
      glomeruli, loops of Henle, collecting and distal tubules, and in the renal
      medulla. As indicated by immunocytochemistry using light microscopy and confirmed
      with the use of reflection confocal microscopy, the enzyme was preferentially
      localized in a perinuclear position in the liver and the renal cells. Subcellular
      fractionation studies followed by enzyme activity assays revealed that a majority
      of the cellular fructose-1,6-bisphosphatase activity was associated to
      subcellular particulate structures. Overall, the data support the concept of
      metabolic zonation in liver as well as in kidney, and establish the concept that
      the Fructose-1,6-bisphosphatase is a particulate enzyme that can not be
      considered a soluble enzyme in the classical sense.

PMID- 8978462
TI  - Interaction of the NG2 proteoglycan with the actin cytoskeleton.
AB  - The NG2 chondroitin sulfate proteoglycan is a membrane-spanning molecule
      expressed by immature precursor cells in a variety of developing tissues. In
      tightly adherent cell lines with a flattened morphology, NG2 is organized on the
      cell surface in linear arrays that are highly co-localized with actin and myosin
      containing stress fibers in the cytoskeleton. In contrast, microtubules and
      intermediate filaments in the cytoskeleton exhibit completely different patterns
      of organization, suggesting that NG2 may use microfilamentous stress fibers as a
      means of cytoskeletal anchorage. Consistent with this is the observation that
      cytochalasin D disrupts the organization of both stress fibers in the
      cytoskeleton and NG2 on the cell surface. Very similar linear cell surface arrays
      are also seen with three other cell surface molecules thought to interact with
      the actin cytoskeleton: the alpha 5 beta 1 integrin, the CD44 proteoglycan, and
      the L1 neuronal cell adhesion molecule. Since the cytoplasmic domains of these
      four molecules are dissimilar, it seems possible that cytoskeletal anchorage in
      each case may occur via different mechanisms. One indication of such differences
      can be seen in colchicine-treated cells which have lost their flattened
      morphology but still retain long actin-positive tendrils as remnants of the actin
      cytoskeleton. NG2 and alpha 5 beta 1 are associated with these tendrils while
      CD44 and L1 are not, suggesting that at least two subclasses of cell surface
      molecules exist which can interact with different subdomains of the actin
      cytoskeleton.

PMID- 8978463
TI  - Cloning, characterization, and expression of the transforming growth factor-beta
      type I receptor promoter in fetal rat bone cells.
AB  - Transforming growth factor (TGF-beta) binds several discrete membrane proteins.
      Of these, a type 1 receptor appears indispensable for signal transduction.
      Previous examination of TGF-beta receptor expression has been limited to changes
      in cell surface protein, and more recently, mRNA abundance. In order to learn
      more about TGF-beta function and receptor expression during osteogenesis, we have
      now cloned a 4 kilobase (kb) DNA fragment 5' proximal to the coding region of the
      rat TGF-beta type I receptor gene. Sequence analysis revealed multiple elements
      compatible with transcription initiation, including a properly positioned and
      oriented CCAAT box, six Sp1 binding sites (three defining GC boxes), and two
      strong AP2 binding sites within a 0.7 kb span directly upstream of the coding
      region. The 3' terminal 0.3 kb span comprises a GC-enriched (77%) so-called CpG
      island that, like other similarly organized promoters, lacks a TATA box. Primer
      extension and RNase protection studies with cRNAs from this area show multiple
      initiation sites within 220 bp 5' proximal to the initial methionine codon.
      Transient transfections using nested, deleted, and inverted promoter sequences
      demonstrated maximal reporter expression by a 1 kb fragment encompassing all of
      these elements. Truncation of the 1 kb fragment from the 5' and 3' ends indicated
      the need for several elements for peak promoter activity. These results, and
      transfections in fetal rat bone and dermal cells, suggest that this promoter
      contains elements that specify basal and conditional expression of the TGF-beta
      type I receptor in bone.

PMID- 8978464
TI  - Basic fibroblast growth factor stimulates phosphatidylcholine-hydrolyzing
      phospholipase D in osteoblast-like cells.
AB  - We examined the effect of basic fibroblast growth factor (bFGF) on the activation
      of phosphatidylcholine-hydrolyzing phospholipase D in osteoblast-like MC3T3-E1
      cells. bFGF stimulated both the formations of choline (EC50 was 30 ng/ml) and
      inositol phosphates (EC50 was 10 ng/ml). Calphostin C, an inhibitor of protein
      kinase C (PKC), had little effect on the bFGF-induced formation of choline. bFGF
      stimulated the formation of choline also in PKC down regulated cells. Genistein
      and methyl 2,5-dihydroxycinnamate, inhibitors of protein tyrosine kinases,
      significantly suppressed the bFGF-induced formation of choline. Sodium
      orthovanadate, an inhibitor of protein tyrosine phosphatases, enhanced the bFGF
      induced formation of choline. In vitro kinase assay for FGF receptors revealed
      that FGF receptor 1 and 2 were autophosphorylated after FGF stimulation. bFGF
      dose-dependently stimulated DNA synthesis of these cells. These results strongly
      suggest that bFGF activates phosphatidylcholine-hydrolyzing phospholipase D
      through the activation of tyrosine kinase, but independently of PKC activated by
      phosphoinositide hydrolysis in osteoblast-like cells.

PMID- 8978465
TI  - Vitamin D analog 25-(OH)-16,23E-Diene-26,27-hexafluoro-vitamin D3 induces
      differentiation of HL60 cells with minimal effects on cellular calcium
      homeostasis.
AB  - Numerous vitamin D3 analogs (VDAs) can inhibit the proliferation of cells from
      several types of human malignancies. The physiologically active form of vitamin
      D3, 1,25-dihydroxyvitamin D3(1,25D3), is formed by successive hydroxylations of
      cholecalciferol at the 25 and 1 alpha positions. In this study we examined the
      effects of the absence of the 1 alpha (OH) group, introduction of a double bond
      in position 16, and further modifications at the 23, 26, and 27 positions in the
      side chain on the potency of the VDAs. The parameters studied were the rapidity
      of the induction of monocytic differentiation, the cell cycle traverse, and the
      effects of VDAs on intracellular calcium homeostasis in HL60 cells. The results
      show that (1) 1,25D3 derivatives which lace the 1 alpha (OH) group have little
      differentiation-inducing activity, (2) hexafluorination (6F) of the terminal
      methyl groups in the side chain partially restores the activity of 1 alpha-desoxy
      compounds and potentiates the activity of 1 alpha hydroxylated compounds, and (3)
      25-(OH)-16,23E-diene-26,27-hexafluoro-vitamin D2 (Ro25-9887) alone among the
      twelve compounds tested induces differentiation with only minimal changes in the
      basal levels of intracellular calcium and store-dependent calcium influx in HL60
      cells. Addition of 1 alpha (OH) group to this compound increases its
      differentiation-inducing activity but also elevates basal calcium level. The
      results suggest that altered calcium homeostasis is not an obligatory component
      of HL60 leukemia cell differentiation, and that Ro25-9887 and related VDAs may be
      suitable for testing as components of anti-leukemic therapy.

PMID- 8978466
TI  - Supporting cells as phagocytes in the olfactory epithelium after bulbectomy.
AB  - Macrophages are known to be phagocytes in the olfactory epithelium of adult rats.
      The participation of other cell types in phagocytosis in association with the
      cell death process was examined in the olfactory epithelium after unilateral
      bulbectomy of neonatal mice. The terminal deoxynucleotidyl transferase (TdT)
      mediated biotinylated dUTP nick end-labeling (TUNEL) method revealed that the
      process of olfactory cell death consists of acute and chronic periods. The number
      of apoptotic cell profiles on the operated side peaked at 1 day, and the
      percentage of labeled cell profiles was 13.6%. The number of dying cells rapidly
      decreased at 3 days and decreased further at 5 days. Only 3% of the cells were
      labeled at 5 days. The percentage of dying cells increased again at the end of
      first postoperative week and remained two- to four-fold higher than control
      values for 2 months (4.7-5.3%). Electron micrographs of sections from early
      postbulbectomy stages (1-7 days) showed that as many as 30% of supporting cell
      profiles contained apoptotic bodies, cellular debris and phagosomes in the
      cytoplasm. The number of supporting cell profiles containing phagosomes declined
      to a plateau 2 weeks following bulbectomy and remained at 8-12% of the supporting
      cell population for 2 months. The results indicate that supporting cells in the
      olfactory epithelium play a significant role in phagocytosis in both acute and
      chronic of cell death after bulbectomy in newborn mice. However, supporting cells
      are not the exclusive phagocytic cell type in the bulbectomized epithelium; a
      small number of macrophages was also observed. Moreover, the phagocytosis by
      supporting cells was observed in unperturbed epithelium in the early stages
      during postnatal development.

PMID- 8978467
TI  - Reciprocal projections of cat extrastriate cortex: I. Distribution and morphology
      of neurons projecting from posterior medial lateral suprasylvian sulcus to area
      17.
AB  - Reciprocal projections between cortical areas have been subdivided into two
      functionally distinct component, "feedforward" and "feedback" (for review, see
      Felleman and Van Essen [1991] Cereb. Cortex 1:1-47). Some anatomical evidence,
      such as differences in the laminar distribution of the neurons of origin and of
      the terminations of their axons, has supported this division. However, very
      little is actually known about the distribution and morphology of the neurons of
      the feedback projections. In order to contribute further to our understanding of
      these two components of the corticocortical projections, I studied the
      distribution and morphology of a feedback projection, the reciprocal projection
      from the posterior medial lateral suprasylvian sulcus (PMLS), to primary visual
      cortex (area 17). Retrograde transport of horseradish peroxidase and fluorescent
      tracers in vivo combined with intracellular dye injections in lightly fixed
      cortical slices revealed many similarities between the feedforward and feedback
      projections: 1) They both emanate from all layers but layer 1; 2) each layer of
      origin contains a wide variety of standard and/or inverted pyramidal neurons; and
      3) all of these, with the exception of a rare, large layer 5 neuron, have
      dendritic fields restricted principally to their layers of origin. There was,
      however, one major difference between the feedforward and feedback projections:
      In contrast to the projection from area 17 to PMLS, the projection from PMLS had
      a dense projection from layer 6 that compromised a striking abundance of spiny
      fusiform and inverted pyramidal neurons. These were morphologically distinct from
      other layer 6 neurons that project to the thalamus. Taken together, these data
      suggest that the reciprocal projections between area 17 and area PMLS, although
      not completely equivalent, share essential features that form a distinct
      population of neurons differing in morphology from corticothalamic projection
      neurons.

PMID- 8978468
TI  - Dynorphin regulates D1 dopamine receptor-mediated responses in the striatum:
      relative contributions of pre- and postsynaptic mechanisms in dorsal and ventral
      striatum demonstrated by altered immediate-early gene induction.
AB  - Dynorphin, an endogenous kappa opioid receptor ligand, acts in the striatum to
      regulate the response of striatonigral neurons to D1 dopamine receptor
      stimulation. We investigated the relative contributions of both presynaptic kappa
      receptors on dopamine terminals and postsynaptic kappa receptors on striatal
      neurons by analyzing opioid regulation of D1 effects in the absence of
      presynaptic kappa receptors, after 6-hydroxydopamine depletion of striatal
      dopamine. D1-receptor-mediated immediate-early gene induction was measured by
      using in situ hybridization histochemistry. First, repeated treatment with the D1
      receptor agonist SKF-38393 (2 mg/kg/day, 3-14 days) was used to increase
      dynorphin levels in rats with dopamine depletions. In the nucleus accumbens,
      increased dynorphin expression was accompanied by reduced induction of the
      immediate-early genes c-fos and zif 268 by SKF-38393. In contrast, in
      dorsal/lateral aspects of the dopamine-depleted striatum, this D1 response was
      sustained despite a large increase in dynorphin expression. These results are
      consistent with a requirement of dopamine terminals (presynaptic kappa receptors)
      for the inhibitory action of dynorphin in the dorsal/lateral striatum, but not in
      the ventral striatum. Second, the kappa receptor agonist spiradoline (1-10 mg/kg)
      reduced c-fos and zif 268 induction by SKF-39393 (2.5 mg/kg) preferentially in
      ventral parts of the dopamine-depleted striatum, which contain higher levels of
      kappa receptor mRNA and binding. These results also indicate that postsynaptic
      kappa receptors contribute to the inhibition of the D1 response at least in the
      ventral striatum. Together, these results indicate that dynorphin in the striatum
      functions to regulate dopamine input to striatonigral neurons, acting at both pre
      and postsynaptic sites, and that the relative contributions of these mechanisms
      differ between dorsal and ventral striatal regions.

PMID- 8978469
TI  - Characterization of the microvascular glycocalyx in normal and injured spinal
      cord in the rat.
AB  - The glycocalyx of microvasculature in normal and injured spinal cord was
      characterized by using cationized ferritin to define anionic sites and the
      lectins concanavalin agglutinin (Con A) and Ricinus communis agglutinin I (RCA)
      to delineate carbohydrate moities. Binding of cationized ferritin was evaluated
      at the ultrastructural level in control animals and at 3 hours after spinal cord
      injury. Horseradish peroxidase (HRP) was administered intravenously before
      euthanasia. In control spinal cord, there was continuous even binding of
      cationized ferritin along the luminal front of microvasculature and no evidence
      of barrier permeability to HRP. After spinal cord injury, there was a reduction
      in binding of cationized ferritin in those regions of spinal cord that exhibited
      barrier breakdown to HRP. Lectin binding in the spinal cord was evaluated at 3
      hours and 3 days postinjury. At the light microscopic level, there appeared to be
      increased binding of Con A and RCA in microvessels by 3 days postinjury as
      compared with the control spinal cord. At the ultrastructural level, a
      significant increase in RCA binding was noted along luminal fronts in the injured
      spinal cord. This increased binding coincided with a significant elaboration of
      the endothelial glycocalyx. These findings demonstrate that the charge,
      structure, and carbohydrate composition of the endothelial glycocalyx in
      microvessels in the spinal cord may be dramatically altered after spinal cord
      injury. Furthermore, there is an association between the loss of charge and
      disruption of the barrier, suggesting that anionic sites may contribute to
      maintenance of the blood-spinal cord barrier.

PMID- 8978470
TI  - Spatial distribution of [14C]2-deoxyglucose uptake in the glomerular layer of the
      rat olfactory bulb following early odor preference learning.
AB  - Previous work has shown that odors induce focal uptake of [14C]2-deoxyglucose (2
      DG) within the glomerular layer of the main olfactory bulb and that the amount of
      2-DG accumulated in these foci increases after early odor learning. To determine
      if learning-associated changes in 2-DG uptake occur across the entire glomerular
      layer, we have mapped uptake throughout the layer at fixed angles in coronal
      sections through the bulb. Resulting arrays for individual bulbs were corrected
      for differing bulb size and averaged across experimental groups to address the
      spatial distribution of uptake. The average arrays revealed at least three
      discrete fields of uptake in naive, peppermint-exposed rats at postnatal day 19
      that were not seen in air-exposed littermates. In agreement with previous
      studies, early preference training with peppermint odor given on postnatal days 1
      18 increased 2-DG uptake at postnatal day 19 within odor-dependent patches of
      uptake in the posterior half of the midlateral bulb, whereas odor-dependent,
      ventrolateral patches of uptake did not increase to the same extent. In addition,
      early preference learning was associated with significantly increased 2-DG uptake
      average over the entire analyzed glomerular layer. These increases were smaller
      than those within odor-dependent foci and were distributed widely across the
      glomerular layer, showing low overlap between trained and control rats in
      anterior regions where peppermint odor did not stimulate 2-DG uptake. The widely
      distributed increases in 2-DG uptake after learning may reflect changed activity
      of centrifugal projections that diffusely innervate the glomerular layer.

PMID- 8978471
TI  - Distribution and hormonal regulation of androgen receptor immunoreactivity in the
      forebrain of the male European ferret.
AB  - The distribution and hormonal regulation of androgen-receptor-immunoreactive (AR
      ir) cells in the male European ferret forebrain were examined. AR-ir cells were
      found in many limbic and hypothalamic structures, and their distribution was
      similar to that reported for cells that either bind androgen or contain AR
      protein or mRNA in other species. Regulation of brain AR immunoreactivity by
      gonadal steroids was brain-region dependent. In most regions examined, including
      the preoptic area, amygdala, and several hypothalamic nuclei, castration reduced
      the density of AR-ir profiles and the intensity of immunocytochemical staining,
      and long-term (days) androgen, but not estrogen, replacement restored these
      parameters of AR immunoreactivity. Other areas, such as the bed nucleus of the
      stria terminalis, appeared to be relatively resistant to modulation of AR
      immunoreactivity by castration and long-term androgen treatment. The ability of
      testosterone to increase AR-ir profile density is not a simple consequence of
      translocation of AR from the cytoplasm to the nucleus, because short-term (hours)
      treatment with testosterone did not result in an increase in AR-ir profile
      density equivalent to that seen after 10 days of testosterone treatment. Thus,
      androgens appear to be able to increase AR levels within certain brain cell
      groups, thereby altering target tissue responsiveness to their own action.

PMID- 8978472
TI  - Differential expression of brain-derived neurotrophic factor and neurotrophin 3
      mRNA in lingual papillae and taste buds indicates roles in gustatory and
      somatosensory innervation.
AB  - Although many studies have demonstrated the dependency of taste bud function
      and/or survival on intact innervation, relatively few have dealt with the
      development of taste bud innervation. Using in situ hybridization histochemistry,
      we show that brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3)
      mRNA are expressed in a specific pattern in the taste buds, tongue papillae, and
      lingual epithelium during development and that expression persists into
      adulthood. BDNF mRNA is expressed in a fraction of the taste cells of the
      developing and adult taste buds in rats, showing different labeling intensities
      among the labeled cells. NT3 and mRNA seems to be located in areas other than
      those where BDNF mRNA is expressed, mainly in the superior epithelial surfaces of
      circumvallate papillae, the outer surface epithelium of foliate papilae, the
      superior surface and the lateral epithelium of the fungiform papillae, and the
      epithelium of the filiform papillae. NT3 mRNA labeling is also observed among
      muscle and connective tissue of the tongue. The morphological appearance,
      expression of NT3 mRNA, and ramification of nerve fibers in defined epithelial
      structures in the posterior wall of the anterior filiform papillae suggest the
      existence of a mechanosensory apparatus in these papillae. Nerve growth factor
      and neurotrophin 4 probes did not give rise to selective labeling in tongue,
      although their presence cannot be totally excluded. Based on present and prior
      studies, we suggest that BDNF is needed during initiation and for maintenance of
      gustatory innervation of taste buds and gustatory papillae and that NT3 is mainly
      needed for somatosensory innervation of the tongue.

PMID- 8978473
TI  - Long-term integration and neuronal differentiation of human embryonal carcinoma
      cells (NTera-2) transplanted into the caudoputamen of nude mice.
AB  - NTera-2 (NT2) cells are a human embryonal carcinoma (EC) cell line derived from a
      teratocarcinoma that differentiate exclusively into postmitotic neurons in vitro
      following retinoic acid (RA) treatment. Like other EC cell lines, NT2 cells
      rapidly form lethal tumors following transplantation into peripheral sites or
      many regions of the brain. However, when grafts are confined to the caudoputamen
      (CP), the NT2 cells differentiate into postmitotic neuronlike cells and do not
      form lethal tumors. To examine the long-term fate of such grafts, we studied NT2
      cell transplants in the CP of nude mice that survived for > 1 year. NT2 cells in
      these grafts acquired molecular markers of fully mature neurons including the
      low, middle, and high molecular weight neurofilament proteins, microtubule
      associated protein 2, tau, and synaptophysin. Furthermore, neuronlike cells in
      long-term CP grafts formed synaptic structures, and their processes became
      myelinated, whereas tyrosine hydroxylase (TH)-positive neuronlike cells in the
      grafts increased with progressively longer postimplantation survival times.
      Soluble extracts of the adult mouse CP augmented TH expression in RA-treated NT2
      cells in vitro. These data suggest that the adult mouse CP is a source of
      factor(s) that inhibits tumor formation and induce a catecholaminergic neuronal
      phenotype in these human NT2 cells in vivo and in vitro. Identification of these
      factors could accelerate efforts to elucidate mechanisms that regulate progenitor
      cell fate and the commitment of neurons to specific neurotransmitter phenotypes.

PMID- 8978474
TI  - Patterns of intrinsic and associational circuitry in monkey prefrontal cortex.
AB  - Both local and long-range connections are critical mediators of information
      processing in the cerebral cortex, but little is known about the relationships
      among these types of connections, especially in higher-order cortical regions. We
      used quantitative reconstructions of the label arising from discrete
      (approximately 350 microns diameter) injections of biotinylated dextran amine and
      cholera toxin B to determine the spatial organization of the axon collaterals and
      principal axon projections furnished by pyramidal neurons in the supragranular
      layers of monkey prefrontal cortex (areas 9 and 46). Both terminals and cell
      bodies labeled by transport along axon collaterals in the gray matter formed
      intrinsic clusters which were arrayed as a series of discontinuous stripes of
      similar size and shape. The co-registration of anterograde and retrograde
      transport confirmed that these convergent and divergent intrinsic connections
      also were reciprocal. Transport from the same injection sites along principal
      axons through the white matter formed associational clusters which were also
      arrayed as a series of discontinuous stripes. The dimensions of the anterogradely
      and retrogradely-labeled associational stripes were very similar to each other
      and to the intrinsic stripes. These findings demonstrate that divergence,
      convergence, and reciprocity characterize both the intrinsic and associational
      excitatory connections in the prefrontal cortex. These patterns of connections
      provide an anatomical substrate by which activation of a discrete group of
      neurons would lead to the recruitment of a specific neuronal network comprised of
      both local and distant groups of cells. Furthermore, the consistent size of the
      intrinsic and associational stripes (approximately 275 by 1,800 microns) suggests
      that they may represent basic functional units in the primate prefrontal cortex.

PMID- 8978475
TI  - Distribution of dopamine immunoreactivity in the rat, cat and monkey spinal cord.
AB  - In the present study, the distribution of dopamine (DA) was identified light
      microscopically in all segments of the rat, cat, and monkey spinal cord by using
      immunocytochemistry with antibodies directed against dopamine. Only fibers and
      (presumed) terminals were found to be immunoreactive for DA. Strongest DA
      labeling was present in the sympathetic intermediolateral cell column (IML).
      Strong DA labeling, consisting of many varicose fibers, was found in all laminae
      of the dorsal horn, including the central canal area (region X), but with the
      exception of the substantia gelatinosa, which was only sparsely labeled,
      especially in rat and monkey. In the motoneuronal cell groups DA labeling was
      also strong and showed a fine granular appearance. The sexually dimorphic
      cremaster nucleus and Onuf's nucleus (or its homologue) showed a much stronger
      labeling than the surrounding somatic motoneurons. In the parasympathetic area at
      sacral levels, labeling was moderate. The remaining areas, like the intermediate
      zone (laminae VI-VIII), were only sparsely innervated. The dorsal nucleus (column
      of Clarke) showed the fewest DA fibers, as did the central cervical nucleus,
      suggesting that cerebellar projecting cells were avoided by the DA projection. In
      all species, the descending fibers were located mostly in the dorsolateral
      funiculus, but laminae I and III also contained many rostrocaudally oriented
      fibers. It is concluded that DA is widely distributed within the spinal cord,
      with few differences between species, emphasizing that DA plays an important role
      as one of the monoamines that influences sensory input as well as autonomic and
      motor output at the spinal level.

PMID- 8978476
TI  - Neurogenesis in neonatal rat brain is regulated by peripheral injection of basic
      fibroblast growth factor (bFGF).
AB  - Many major diseases of human brain involve deficiencies of select neuronal
      populations. As one approach to repair, we examined regulation of neurogenesis
      directly in vivo, employing postnatal day 1 (P1) cerebellar cortex, which is
      composed primarily of granule neurons and dividing precursors. We focused on
      basic fibroblast growth factor (bFGF), which stimulates precursor mitosis in
      culture and which is highly expressed in cerebellum during neurogenesis.
      Subcutaneous injection of bFGF increased [3H]thymidine ([3H]dT) incorporation, a
      marker for DNA synthesis, by 50% in whole cerebellar homogenates, suggesting that
      peripherally administered factor altered ongoing neural proliferation. Further,
      assay of isolated granule precursors revealed a 4-fold increase in [3H]dT
      incorporation following in vivo bFGF treatment, indicating that granule
      neuroblasts were the major bFGF-responsive population. Morphologic analysis
      indicated that twice as many granule precursors were in S-phase of the mitotic
      cycle after peripheral bFGF. To determine whether other neurogenetic populations
      respond to peripheral bFGF, we examined additional brain regions in vivo. bFGF
      stimulated DNA synthesis by 68% in hippocampus, and by > 250% in pontine
      subventricular zone (SVZ). In contrast, incorporation was not altered in basal
      pons or cerebral cortex, regions in which neurogenesis has already ceased. To
      define potential direct actions of peripherally administered factor, 125I-bFGF
      was used to study distribution. Intact 18 kDa 125I-bFGF was recovered from brain
      following peripheral injection, suggesting that the factor acted directly to
      stimulate mitosis in dividing neuroblasts. The stimulation of neuronal
      proliferation by exogenous bFGF suggests that the factor normally regulates
      neurogenesis, and provides new therapeutic approaches to promote functional
      recovery from nervous system diseases.

PMID- 8978477
TI  - In vivo morphometry of the intrasulcal gray matter in the human cingulate,
      paracingulate, and superior-rostral sulci: hemispheric asymmetries, gender
      differences and probability maps.
AB  - Volumes of the intrasulcal gray matter were measured in three cerebral sulci
      located on the medial wall of the human frontal lobe: cingulate sulcus (CS),
      paracingulate sulcus (PCS), and superior-rostral sulcus (SRS). The measurements
      were carried out on T1-weighted 3-D high-resolution magnetic-resonance (MR)
      images acquired in 105 young right-handed volunteers (42 female and 63 male).
      Before the measurement, the images were transformed into a standardized
      stereotaxic space (Talairach and Tournoux [1988] Human Brain: 3-Dimensional
      Proportional System. An Approach to Cerebral Imaging. Stuttgart, New York: Georg
      Thieme Verlag), thus removing inter-individual differences in brain size. The
      intrasulcal gray matter was segmented in a semi-automatic manner. Significant
      gender differences were found in the volume of the CS (female > male) and the PCS
      (male > female). Hemispheric asymmetries were observed between the left and right
      volumes of the intrasulcal gray matter in the anterior (right > left) and
      posterior (left > right) segments of the CS, as well as between the left and
      right volumes of the PCS (left > right). There was no interaction between the
      asymmetries and gender. In addition, significant positive correlations were found
      between the left and right gray-matter volumes in the anterior (r = 0.43) and
      posterior (r = 0.66) segments of the CS, whereas significant negative
      correlations were observed between the gray-matter volumes of the anterior
      segment of the CS and those of the PCS (left hemisphere: r = -0.48; right
      hemisphere: r = -0.42). The observed hemispheric asymmetries in the CS and PCS
      gray-matter volumes are consistent with the proposed role of these structures in
      the integration of emotions with cognition (CS) and in the control of
      speech/vocalization (PCS). The pattern of inter-hemispheric correlations in the
      sulcal gray-matter points to an increasing asynchrony in the foetal development
      of primary (CS), secondary (SRS), and tertiary (PCS) sulci, respectively. The
      presence of negative correlations between the two neighbouring sulci (CS and PCS)
      suggests that a process of compensation could underlie interactions between
      adjacent primary and tertiary sulci. Besides the above volumetric analysis, we
      also provide average (probability) maps of the three sulci; the use of such maps
      for the parcellation of the medial frontal lobe and localization of "peaks"
      obtained in blood-flow activation studies is discussed.

PMID- 8978478
TI  - Metabolic fate of oleic acid derived from lysosomal degradation of cholesteryl
      oleate in human fibroblasts.
AB  - Low density lipoprotein cholesteryl [14C]oleate (LDL-[14C]CO) was used as a tool
      to label lysosomes with cholesteryl [14C]oleate (CO) and to follow subsequently
      the metabolic processing of oleic acid released by acid lipase. Liberated
      [14C]oleate was incorporated into glycerolipids, mainly into phosphatidylcholine.
      Incubations in the presence of various concentrations of exogenously added oleic
      acid and double label experiments showed that oleic acid derived from lysosomal
      degradation of CO and exogenously added oleic acid distributed in a similar
      fashion among triacylglycerol and various phospholipids. To further study the
      metabolism of LDL-derived oleic acid, experiments were performed in which
      fibroblasts were prelabeled with LDL-[14C]CO. The subsequent processing of
      lysosome-derived oleic acid was followed with time without LDL-[14C]CO in the
      medium. From these experiments it became clear that apart from the esterification
      into glycerolipids a substantial part of lysosome-derived oleic acid was released
      into the medium. The efflux of oleic acid into the medium preceded the
      incorporation into glycerolipids, was dependent on the composition of the
      extracellular medium, and was energy-independent. Our data are compatible with a
      mechanism in which lysosome-derived fatty acids are transported to the plasma
      membrane prior to transport to endoplasmic reticulum for esterification. Intra-
      and extra-cellular factors influence the distribution of lysosome-derived oleic
      acid among cells and medium.

PMID- 8978479
TI  - Cholesta-5,7,9(11)-trien-3 beta-ol found in plasma of patients with Smith-Lemli
      Opitz syndrome indicates formation of sterol hydroperoxide.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder
      characterized by accumulation of cholesta-5,7-dien-3 beta-0l caused by a
      deficiency of the enzyme desaturating this sterol to cholesterol. In addition to
      other unusual sterols recently found in plasma of patients with SLOS, namely
      cholesta-5,8-dien-3 beta-ol and 19-nor-cholesta-5,7,9 (10)-trien-3 beta-ol we
      have detected a trienol and we describe here its identification as cholesta-5,7,9
      (11)-trien-3 beta-ol by GC-MS and by comparison with a synthetic standard. We
      tested the possibility that the trienol may be formed by radical oxidation of
      cholesta-5,7-dien-3 beta-ol accumulated in plasma of patients with SLOS because
      it is known to be formed by decomposition of 7-hydroperoxy-cholesta-5,8-dien-3
      beta-ol, which is a product of cholesta-5,7-dien-3 beta-ol photooxidation.
      Incubation of cholesta-5,7-dien-3 beta-ol with rat liver microsomes in the
      presence of ADP/Fe2+ and NADPH gave rise to a number of oxygenated sterols. Among
      these, analysis by particle-beam LC-MS under CI conditions indicated the presence
      of 7-hydroperoxy-cholesta-5,8-dien-3 beta-ol and of cholesta-5,7,9(11)-trien-3
      beta-ol which is known to derive from the oxidation of the 7-hydroperoxide. From
      these results we conclude that cholesta-5,7-dien-3 beta-ol accumulated in tissues
      of patients with SLOS may be oxidized by oxygen radicals giving rise to
      oxygenated sterols. Some of these compounds may be toxic and may contribute to
      worsen the pathological picture in patients with SLOS.

PMID- 8978480
TI  - Phytanic acid activation in rat liver peroxisomes is catalyzed by long-chain acyl
      CoA synthetase.
AB  - In Refsum disease, disorders of peroxisome biogenesis, and rhizomelic
      chondrodysplasia punctata, pathological accumulation of phytanic acid results
      from impaired alpha-oxidation of this branched-chain fatty acid. Previous studies
      from this laboratory indicated that activation of phytanic acid to its CoA
      derivative precedes its alpha-oxidation in peroxisomes. It was reported that this
      reaction is catalyzed by a unique phytanoyl-CoA synthetase in human peroxisomes.
      We wanted to determine whether phytanic acid activation in rats required long
      chain acyl-CoA synthetase (LCS), very long-chain acyl-CoA synthetase (VLCS), or a
      different enzyme. To test directly whether LCS could activate phytanic acid, rat
      liver cDNA encoding this enzyme was transcribed and translated in vitro. The
      expressed enzyme had both LCS activity (assayed with palmitic acid, C16: 0) and
      phytanoyl-CoA synthetase activity; VLCS activity (assayed with lignoceric acid,
      C24: 0) was not detectable. The ratio of phytanoyl-CoA synthetized activity to
      palmitoyl-CoA synthetase activity for LCS synthetized in vitro (approximately
      205) was higher than that observed in peroxisomes isolated from rat liver (5
      10%), suggesting that the expressed enzyme contained sufficient phytanoyl-Coa
      synthetase activity to account for all activity observed in intact peroxisomes.
      Further experiments were carried out to verify that phytanic acid was activated
      by LCS in rat liver peroxisomes. Attempts to separate LCS from phytanoyl-CoA
      synthetase by chromatography on several matrices were unsuccessful. Preparative
      isoelectric focusing revealed that phytanoyl-CoA synthetase and LCS had
      indistinguishable isoelectric points. Phytanoyl-CoA synthetase activity was
      inhibited by unlabeled palmitic acid but not by lignoceric acid. Heat treatment
      inactivated both phytanoyl-CoA and palmitoyl-CoA synthetase activities at similar
      rates. 5,8,11,14-Eicosatetraynoic acid inhibited activation of phytanic acid and
      palmitic acid in a parallel dose-dependent manner, whereas activation of
      lignoceric acid was not affected. These data support our conclusion that rat
      liver LCS, an enzyme known to be present in peroxisomal membranes, has phytanoyl
      CoA synthetase activity.

PMID- 8978481
TI  - Monomethylethanolamine reduces plasma triacylglycerols and apolipoprotein B and
      increases apolipoprotein A-I rats without induction of fatty liver.
AB  - Monomethylethanolamine (MME) inhibits very low density lipoprotein (VLDL)
      secretion from cultured rat hepatocytes by disruption of translocation of
      apolipoprotein (apo) B across the endoplasmic reticulum membrane (A. E. Rusinol,
      E. Y. W. Chan and J. E. Vance. 1993. J. Biol. Chem. 268: 25168-25175). We have
      now investigated whether or not plasma levels of lipids and apoB are reduced by
      dietary supplementation of rats with MME. In rats fed MME for 5 to 7 days, the
      levels of triacylglycerols and apoB in VLDL were reduced by 66% and 45%,
      respectively. At the same time, MME feeding also increased plasma apoA-I by 80%.
      No significant differences were found in body or liver weights between control
      and MME-fed rats, nor did the reduction of plasma VLDL in MME-fed rats result in
      accumulation of triacylglycerols in the liver. When the dietary period was
      extended to 15 weeks, essentially the same results were obtained except that
      plasma cholesterol was increased by 31% in MME-treated animals, apparently
      because of increased amounts of apoA-I and high density lipoproteins. According
      to post-mortem and microscopic examination, rats fed MME for 15 weeks were
      anatomically normal with no indication of any lipid accumulation in the liver.
      The ability of MME to reduce VLDL secretion and at the same time to increase the
      level of high density lipoproteins are attractive properties of a therapeutic
      agent for treatment of atherosclerosis in humans.

PMID- 8978482
TI  - Differential scanning calorimetry study of the influence of phospholipid analogs
      with a carbonyl-terminated sn-2 chain on the interdigitated phases formed by 1
      stearoyl-2-capryl-sn-glycero-3-phosphatidylcholine (C18:C10-PC).
AB  - Synthetic glycerophosphocholines with highly asymmetric chain lengths form
      interdigitated bilayers in the gel phase. In nature, phospholipids with one
      hydrocarbon chain approximately twice as long as the other can arise from the
      autooxidation of unsaturated linkages in the acyl chain, and thus the oxidation
      products would contain a carbonyl group at the chain terminus. In this study, we
      have investigated the thermotropic behavior of bilayers prepared from mixtures of
      the well-studied, mixed-chain phospholipid, 1-stearoyl-2-capryl-sn-glycero-3
      phosphocholine (C18:C10-PC, 1), with synthetic 1-stearoyl-2-acyl-sn-glycero-3
      phosphocholines in which the sn-2 chain is approximately one-half the length of
      the sn-1 chain and contains a C==O group near the omega terminus. Phase diagrams
      of binary mixtures of 1 with a chain-terminal ketone-PC analog (2) or with a
      chain-terminal ester-PC analog (3) in excess water exhibited gel-phase
      immiscibility over a wide compositional range, but miscibility in the liquid
      crystalline phase. However, 1 was completely miscible with C18:C10:1 delta 10-PC
      (compound 4), which bears a chain-terminal carbon-carbon double bond, in both the
      gel and liquid-crystalline phases. The calorimetric data suggest that
      phosphatidylcholines (PC) with carbonyl-terminated chains, which can be produced
      by autooxidation of naturally abundant 1-saturated-2-unsaturated phospholipids
      such as 1-stearoyl-2-oleoyl-PC, may not form the normal triple-chain mixed
      interdigitated structure characteristic of hydrocarbon-terminated PCs in gel
      phase bilayers.

PMID- 8978483
TI  - Dietary linoleic acid increases and palmitic acid decreases hepatic LDL receptor
      protein and mRNA abundance in young pigs.
AB  - The present study was conducted to determine the effects of dietary fatty acids
      on hepatic LDL receptor (LDLr) protein abundance and mRNA levels. Sixty pigs were
      randomized into 10 groups and fed corn-soybean meal diets containing three
      cholesterol levels (0.25%, 0.5%, and 1.0%, w/w) with no added fat, or fats rich
      (30% of calories) in palmitic acid or linoleic acid. A control group was fed the
      base diet with no added fat. After 30 days, plasma LDL-cholesterol (LDL-C) levels
      increased as the dietary cholesterol increased (P < 0.05); however, there was no
      significant effect of either fatty acid. Dietary fatty acids, however, had
      distinctly different effects on hepatic LDLr protein (analyzed by ELISA) and mRNA
      (analyzed by Northern blot) abundance. When pigs consumed diets containing 0.25%
      cholesterol, linoleic acid increased hepatic LDLr protein 40% whereas palmitic
      acid reduced it 40% (P < 0.05). These changes in LDLr protein abundance were
      accompanied by parallel changes in hepatic LDLr mRNA; linoleic acid increased
      LDLr mRNA 2-fold (P < 0.01), whereas palmitic acid decreased it 60% (P < 0.01).
      The differential effects of fatty acids on LDLr expression were only observed at
      0.25% cholesterol, suggesting that higher intakes of cholesterol have a dominant
      and repressive effect on regulation of LDLr expression. Cholesterol intake
      increased hepatic total cholesterol levels (P < 0.01) while dietary fatty acids
      had no effect on hepatic sterols. In summary, our results indicate that dietary
      linoleic acid and palmitic acid have markedly different effects on hepatic LDLr
      protein abundance that are mediated by differential effects on LDLr mRNA and
      protein levels. Further studies are needed to fully elucidate the molecular
      mechanisms by which fatty acids regulate LDLr mRNA and protein levels.

PMID- 8978484
TI  - Identification of promoter sequences in the 5' untranslated region of the baboon
      apolipoprotein[a] gene.
AB  - Like humans, baboons possess apolipoprotein[a] (apo[a]), a unique protein
      component of the atherogenic lipoprotein [a] (Lp[a]) particle. Baboon apo[a] also
      exhibits extensive variation with respect to size and serum levels. In this
      report, we have cloned the 5' flanking region of the baboon apo[a] gene (I
      isoform) and performed promoter mapping studies to identify sequences that
      control apo[a] transcription. The sequence of the baboon apo[a] 5' flanking
      region is similar to the human gene, and contains two Alu repeats that
      distinguish the apo[a] gene from plasminogen and other apo[a]-like genes. The
      transcription start site for the baboon apo[a]gene is located 85 bp upstream from
      the major start site for the human apo[a] gene. For promoter mapping studies, we
      constructed two sets of deletion clones (5' to 3' and 3' to 5') in luciferase
      reporter plasmids for transfection of hepatic cell lines (HepG2 and HUh7). These
      experiments showed that the 5' untranslated region (5' UTR) contains a positive
      promoter element with 85% identity to the consensus binding site for hepatocyte
      nuclear factor 1 alpha (HNF-1 alpha), and a negative element that is functional
      in HepG2 cells, but not Huh7 cells. Transfection assays with HeLa cells showed
      that the positive promoter element acts in an hepatocyte-specific manner. We also
      cloned the 5' flanking region from a baboon carrying a null allele that produced
      no detectable hepatic transcripts or serum isoforms in vivo. Surprisingly, the 5'
      flanking regions of the null allele possessed a promoter that was functional in
      transfection assays. We conclude that the baboon apo[a] gene 5'UTR contains
      hepatocyte-specific promoter elements, but that other unknown sequences must
      influence apo[a] expression in vivo.

PMID- 8978485
TI  - Translational regulation of lipoprotein lipase by thyroid hormone is via a
      cytoplasmic repressor that interacts with the 3' untranslated region.
AB  - To better characterize the increase in lipoprotein lipase (LPL) translation by
      hypothyroidism, adipocytes were prepared from control and hypothyroid rats.
      Whereas LPL synthesis was higher in hypothyroid adipocytes, with no change in
      mRNA levels, there was no increase in hormone-sensitive lipase (HSL) synthesis.
      To determine whether a transacting translation regulatory factor was present, a
      cytoplasmic fraction was prepared from control and hypothyroid adipocytes, and
      added to an in vitro translation system containing the hLPL mRNA. The hypothyroid
      cell fraction from adipose and heart yielded an increase in LPL translation, when
      compared to control extracts. Further experiments determined that the control
      adipocyte extract contained a translation-inhibitory factor that was 8-fold lower
      in activity in the hypothyroid extract. Using different LPL mRNA constructs in
      the in vitro translation reaction, the region that controlled translation was
      localized to nucleotides 1599 to 1638 (proximal 3' untranslated region (UTR)). To
      confirm the presence of a transacting factor, a sense RNA strand corresponding to
      this region was added to the in vitro translation reaction. This sense strand
      competed for the transacting factor in the control cell extract, yet had no
      effect on the hypothyroid cell extract. Thus, there is a translation repressor
      factor in the cytoplasm of rat adipocytes, and this factor is greatly reduced in
      activity in hypothyroid rat adipocytes. Because a similar mechanism of LPL
      regulation occurs in response to epinephrine, the absence of the translation
      repressor may be a mechanism for the loss of sensitivity of hypothyroid cells for
      catecholamines.

PMID- 8978486
TI  - Characterization of the murine phosphatidylethanolamine N-methyltransferase-2
      gene.
AB  - Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes the conversion of
      phosphatidylethanolamine to phosphatidylcholine in the mammalian liver via three
      sequential methylations. In the present studies, we cloned and characterized the
      murine gene for PEMT2, the isoform of the enzyme that localized to the
      mitochondria-associated membrane. The structure of the gene was determined by
      analysis of two lambda and three P1 genomic clones, and compared to the known rat
      PEMT2 cDNA sequence. Southern blotting of mouse genomic DNA indicated that PEMT2
      is a single-copy gene. The gene spans at least 35 kb, with seven exons and six
      introns. Two transcription start sites, 139 and 148 base pairs upstream of the
      translation start site, were detected by primer extension and reverse
      transcriptase-polymerase chain reaction. These experiments indicated that the
      PEMT2 gene is transcribed from a single promoter. Finally, the PEMT2 gene was
      localized to mouse chromosome 11 by interspecific backcrossing. These experiments
      represent the first cloning and characterization of a full-length mammalian gene
      involved in phospholipid biosynthesis.

PMID- 8978487
TI  - Metabolism of hydroperoxy-phospholipids in human hepatoma HepG2 cells.
AB  - Two enzymatic mechanisms have been proposed for the metabolism of hydroperoxy
      phospholipids: i) the combined action of phospholipase A2 and glutathione
      peroxidase, and/or ii) direct enzymatic reduction. The latter reaction may be
      catalyzed by selenium-dependent phospholipid hydroperoxide glutathione peroxidase
      and/or by glutathione S-transferase alpha. To study the pathway of this reaction,
      we used human hepatoma HepG2 cells into which was incorporated labeled,
      hydroperoxy-phospholipids. The major product of incorporated l-palmitoyl-2-(13
      hydroperoxy-cis-9, trans-11-octadecadienoyl)-L-3-phosphatidylcholine was the
      corresponding hydroxy-phospholipid with no hydroxy- or hydroperoxy-fatty acids.
      The contributions to reduction of hydroperoxy-phospholipids in HepG2 cells from
      glutathione S-transferase Al and phospholipid hydroperoxide glutathione
      peroxidase were calculated to be 0.5% and 99.5%, respectively. Increasing
      selenium in the cell culture medium led to increases in selenium-dependent
      phospholipid hydroperoxide glutathione peroxidase activity but not in glutathione
      S-transferase alpha. This increase in the selenium-dependent enzyme was
      paralleled by a concomitant increase in the extent of reduction of the
      incorporated hydroperoxy-phospholipid. We conclude that the main metabolic fate
      of hydroperoxy-phospholipids in HepG2 cells is by direct reduction to hydroxy
      phospholipids by phospholipid hydroperoxide glutathione peroxidase but also by
      glutathione S-transferase alpha, and that phospholipase A2/selenium-dependent
      glutathione peroxidase does not play a significant role in the reduction.

PMID- 8978488
TI  - Formation of oxysterols during oxidation of low density lipoprotein by
      peroxynitrite, myoglobin, and copper.
AB  - Oxidation of low density lipoprotein (LDL) in the artery wall leads to the
      formation of cholesterol oxidation products that may result in cytotoxicity.
      Different mechanisms could contribute to LDL oxidation in vivo resulting in
      characteristic and specific modification of the cholesterol molecule.
      Alternatively, attack on cholesterol by chain propagating peroxyl radicals could
      result in the same distribution of oxidation products irrespective of the initial
      pro-oxidant mechanism. To distinguish between these possibilities we have
      monitored the formation of nine oxysterols during LDL oxidation, promoted by
      copper, myoglobin, peroxynitrite, or azo bis amidino propane. Regardless of the
      oxidant used, the pattern of oxysterol formation was essentially the same. The
      yields of products identified decreased in the order 7-oxocholesterol > 7 beta
      hydroxycholesterol > 7 alpha-hydroxycholesterol > 5,6 beta-epoxycholesterol > 5,6
      alpha-epoxycholesterol except in the case of peroxynitrite in which case a higher
      yield of 5, 6 beta-epoxycholesterol relative to 7-oxocholesterol was found. No
      formation of cholestane 3 beta, 5 alpha, 6 beta-triol, or the 24-,25-,27
      hydroxycholesterols was seen. Concentration of 7-oxocholesterol levels in LDL was
      positively correlated with the degree of protein modification. Endogenous alpha
      tocopherol in LDL or supplementation with butylated hydroxytoluene prevented
      oxysterol formation. Taken together these data indicate that the oxidation of
      cholesterol and protein in LDL occur as secondary oxidation events consequent on
      the attack of fatty acid peroxyl/alkoxyl radicals on the 7-position of
      cholesterol, and with amino acids on apoB. Furthermore, oxidant processes with
      atherogenic potential, such as peroxynitrite, copper, and myoglobin are capable
      of producing oxidized LDL containing cytotoxic mediators.

PMID- 8978489
TI  - Hypocholesterolemic actions of atorvastatin are associated with alterations on
      hepatic cholesterol metabolism and lipoprotein composition in the guinea pig.
AB  - Guinea pigs were fed 15% (w/W) fat, high in lauric and myristic acids, a diet
      known to produce hypercholesterolemia in these animals. The diet was given alone
      or in combination with four doses of atorvastatin equivalent to 1, 3, 10, and 20
      mg/kg per day. Atorvastatin reduced plasma LDL cholesterol concentrations by 46,
      50, 53, and 70%, respectively (P < 0.001). Plasma apoB concentrations were
      reduced by atorvastatin (P < 0.001) and compositional changes occurred in VLDL
      and LDL with reductions of the relative proportion of cholesteryl ester and
      increases in triacylglycerol. A reduction in hepatic cholesteryl ester (66%) was
      observed only with the highest atorvastatin dose (20 mg/kg per day) while
      microsomal cholesterol was reduced by 30% with 3-20 mg/kg per day. Hepatic ACAT
      activity was down-regulated and apoB/E receptor number was increased by
      atorvastatin. In contrast, HMG-CoA reductase activity and cholesterol 7 alpha
      hydroxylase were not affected by the drug. VLDL apoB secretion rates were
      decreased by atorvastatin treatment 59 and 76% with 3 and 20 mg/kg per day,
      respectively. Nascent VLDL particles were larger after drug treatment, showing an
      increased number in triacylglycerol molecules. These results support the
      hypothesis that the plasma LDL lowering induced by atorvastatin is due to a
      decreased secretion of apoB in combination with an increase of hepatic apoB/E
      receptors.

PMID- 8978490
TI  - Effects of weekly LDL-apheresis on metabolic parameters of apolipoprotein B in
      heterozygous familial hypercholesterolemia.
AB  - Apheresis is a treatment option for patients with severe hypercholesterolemia and
      coronary artery disease. It is, however, unknown whether such therapy changes
      kinetic parameters of lipoprotein metabolism, such as apolipoprotein B (apoB)
      secretion rates, conversion rates, and fractional catabolic rates (FCR). We
      studied the long-term effect of regular apheresis therapy on metabolic parameters
      of apoB in five patients with heterozygous familial hypercholesterolemia (FH)
      using endogenous labeling with D3-leucine, mass spectrometry, and
      multicompartmental modeling. Patients were studied prior to (study 1) and after 3
      6 months of weekly apheresis therapy (study 2). LDL-apoB concentration was 183 +/
      16 mg d-1 prior to apheresis therapy (study 1), 135 %/- 7 mg. dl-1 at the
      beginning of study 2, and 163 +/- 10 mg . dl-1 at the end of study 2. VLDL-apoB
      and IDL-apoB were not different between the two studies and did not change during
      study 2. Separate modeling of the two studies revealed very similar parameters in
      each patient. In a second step simultaneous modeling of both studies was
      performed taking the changing pool size as a non-steady-state condition into
      account. ApoB tracer data of both kinetic studies and the change in pool size
      could be described with one set of kinetic parameters (VLDL-apoB FCR 4.32 +/-
      1.06 d-1, LDL-apoB FCR 0.17 +/- 0.05 d-1, apoB secretion rate 11.9 +/- 3.7 mg .
      kg-1 . d-1). These parameters are well within the range of those previously
      published for FH heterozygotes in steady state. We conclude that regular
      apheresis therapy did not alter kinetic parameters of apoB metabolism in these
      patients with heterozygous FH in the long term and that the decreased rate of
      delivery of neutral lipids or apoB to the liver does not regulate plasma apoB
      metabolism.

PMID- 8978491
TI  - Dimeric lipoprotein lipase is bound to triglyceride-rich plasma lipoproteins.
AB  - Lipoprotein lipase hydrolyzes the triglyceride-rich core of chylomicrons and very
      low density lipoproteins. It is also a ligand, in vitro, for binding of
      lipoproteins to the low density lipoprotein receptor-related protein and may play
      a central role in the receptor-mediated removal of triglyceride-rich
      lipoproteins. The aim of the present study was to determine to which lipoprotein
      subclass the enzyme is bound in preheparin plasma and when released into plasma
      by heparin injection. Tetrahydrolipstatin, a potent inhibitor of serine lipases,
      was used to block lipolytic activity, thereby preventing changes in plasma
      lipoproteins due to ex vivo lipolysis. To analyze the distribution pattern of
      lipoprotein lipase dimers among lipoprotein classes, a specific ELISA was used
      and gel filtration was performed in pre- and postheparin plasma from five
      subjects with triglyceride ranging from 69 to 522 mg/dl. When lipolytic activity
      was not inhibited, lipoprotein lipase dimers eluted in association with low and
      high density lipoproteins, reproducing results previously obtained by several
      groups of investigators. However, in pre- and postheparin samples treated with
      tetrahydrolipstatin, most of the dimeric enzyme was found associated with very
      low density lipoprotein particles. In conclusion in pre- and postheparin samples
      most of the lipoprotein lipase dimers are associated with very low density
      lipoproteins when ex vivo lipolytic activity is inhibited, which supports the
      hypothesis that, in vivo, lipoprotein lipase may affect the receptor-mediated
      removal of these particles. Moreover, it suggests that the association between
      lipoprotein lipase and cholesterol-rich lipoproteins might be an ex vivo
      phenomenon due to lack of inhibition of lipolytic activity.

PMID- 8978492
TI  - A comparative study of sterol absorption in different small-intestinal brush
      border membrane models.
AB  - We reported previously that the absorption of cholesterol and long-chain
      cholesteryl esters by rabbit small-intestinal brush border membranes (BBMV) is
      protein-mediated (Thurnhofer, H., and H. Hauser. 1990. Biochemistry. 29:2142
      2148; Compassi, S., M. Werder, D. Boffelli, F. E. Weber, H. Hauser, and G.
      Schulthess. 1995. Biochemistry. 34: 16473-16482). Evidence is presented for
      similar cholesterol transport activities in rabbit, pig, and human BBMV. As BBMV
      are subject to a number of limitations and the influence of these on sterol
      absorption is unknown, it is desirable to verify results obtained with this model
      system in other brush border membrane models more closely related to the in vivo
      situation. Sterol absorption in intact enterocytes parallels the absorption
      measured in BBMV, provided that both model systems are normalized to equal
      sucrase activity. The parallel behavior of the two brush border membrane models
      lends support to our previous conclusion that the brush border membrane takes up
      free and esterified cholesterol in a facilitated and energy-independent process.
      The absorption of sterols in small-intestinal segments mounted in the Ussing
      chamber is shown to be a complex process in which the diffusion of the bile salt
      micelles to the brush border membrane is rate-limiting. All brush border membrane
      models share the disadvantage of being unstable and subject to degradation. The
      seriousness of the problem increases apparently with the complexity of the model,
      i.e., in the order BBMV-->enterocytes-->intestinal segments. One main conclusion
      of this study is that no brush border membrane model is sufficient and
      satisfactory, therefore conclusive work in lipid absorption can never be based on
      a single brush border membrane model.

PMID- 8978493
TI  - Aberrantly spliced mRNAs of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL)
      gene with a donor splice-site point mutation produce hereditary HL deficiency.
AB  - A novel point mutation in the 3-hydroxy-3methyl-glutaryl coenzyme A lyase gene
      was found in a Turkish patient with homozygous 3-hydroxy-3-methylglutaric
      acidemia. Amplification by RT-PCR of the mRNA using a six different pairs of
      oligonucleotides produced no differences in four of the fragments amplified with
      respect to the control, but generated two fragments of different size. One was
      representative of a deletion of 126 bp and the other of an insertion of 78 bp.
      These abnormal mRNAs resulted from a G-->C transversion at the nucleotide +1 of
      an intron, which changed the invariant GT dinucleotide of the 5' donor splice
      site. This was associated with the occurrence of an alternative splicing, which
      led to the skipping of the whole exon of 126 bp, and also with the activation of
      one cryptic donor splice site in the same intron. These aberrant spliced mRNAs
      are predicted to encode two abnormal HMG-CoA lyase proteins: the first results in
      a protein with an internal deletion of 42 amino acids, whose enzyme activity is
      largely abolished, as the catalytic site was completely removed; the second
      contains 17 missense amino acids that precede a stop codon. Northern blot
      analysis showed that the overall content of these aberrantly spliced mRNAs in
      proband fibroblasts was the same as that found in control fibroblasts. However,
      hardly any transcript was observed corresponding to the inserted mutated mRNA
      when it was examined by a specific probe. To quantify the relative proportion of
      the two mRNAs, a quantitative RT-PCR (the DNA-mimic PCR reaction) was carried
      out. Results show that the proportion of the inserted mRNAs with respect to the
      deleted mRNA is only 1.2%. The father, mother, and two brothers of the proband
      were heterozygous in the G-->C mutation in the +1 nucleotide of the intron
      considered, while the two alleles of another brother were free of the mutation.

PMID- 8978494
TI  - Measurement of 3 beta-hydroxysteroid delta 7-reductase activity in cultured skin
      fibroblasts utilizing ergosterol as a substrate: a new method for the diagnosis
      of the Smith-Lemli-Opitz syndrome.
AB  - A new sensitive and specific method for the evaluation of 3 beta-hydroxysteroid
      delta 7-reductase activity, the defective enzyme in the Smith-Lemli-Opitz (SLO)
      syndrome, is described. The assay is based on the use of gas chromatography-mass
      spectrometry with selected-ion monitoring to measure the mass of brassicasterol
      (ergosta-5,22-dien-3 beta-ol) produced by the incubation of ergosterol (ergosta
      5,7,22-trien-3 beta-ol) with cultured human skin fibroblasts. Although the
      conversion of ergosterol to brassicasterol was slower than the transformation of
      [3H]7-dehydrocholesterol to [3H] cholesterol, cells from control subjects
      produced brassicasterol efficiently. In contrast, cells form SLO patients
      produced very little brassicasterol (P < 0.0001, patients vs. parents or vs.
      controls). These results indicate that the reduction of ergosterol can be used as
      an assay for 3 beta-hydroxysteroid delta 7-reductase in human skin fibroblasts,
      which avoids the many problems caused by the instability and lack of availability
      of radiolabeled 7-dehydrocholesterol. The present method made it possible to
      diagnose the SLO syndrome with high sensitivity and reliability using a
      commercially available compound.

PMID- 8978495
TI  - Lipoprotein lipase degradation by adipocytes: receptor-associated protein (RAP)
      sensitive and proteoglycan-mediated pathways.
AB  - Lipoprotein lipase (LPL), the major enzyme responsible for the hydrolysis of
      triglycerides, is primarily synthesized by adipocytes and myocytes. In addition
      to synthesis, degradation of cell surface-associated LPL is thought to be
      important in regulating production of the enzyme. We studied LPL metabolism in
      the LPL synthesizing adipocyte cell line BFC-1 beta and assessed the
      contributions of cell surface heparan sulfate proteoglycans (HSPG), low density
      lipoprotein receptor related protein (LRP), and glycosylphosphatidylinositol
      (GPI)-linked proteins to LPL uptake and degradation by these cells. Adipocytes
      degraded 10-12% of total cell surface I-labeled LPL in 2 h and 23-28% in 4 h. In
      1 h, 30-54% of the degradation was inhibited by the 39 kDa receptor associated
      protein (RAP), an inhibitor of ligand binding to LRP. At 4 h, only 19-23% of the
      LPL degradation was RAP inhibitable. This suggested that two pathways with
      different kinetics were important for LPL degradation. Heparinase/heparitinase
      treatment of cells showed that most LPL degradation required the presence of
      HSPG. Treatment with phosphatidylinositol-specific phospholipase C (PIPLC)
      inhibited 125I-labeled LPL degradation by 13%. However, neither RAP nor PIPLC
      treatment of adipocytes significantly increased the amount of endogenously
      produced LPL activity in the media. To determine whether direct uptake of LPL
      bound to HSPG could account for the non-RAP sensitive LPL uptake and degradation,
      proteoglycan metabolism was assessed by labeling cells with 35SO4. Of the total
      pericellular proteoglycans, 14% were PIPLC releasable; surprisingly, 30% were
      dissociated from the cells with heparin. The amount of labeled pericellular
      proteoglycans decreased 26% in 2 h and 50% in 8 h, rapid enough to account for at
      least half of the degradation of cell surface LPL. We conclude that adipocytes
      degrade a fraction of the cell surface LPL, and that this process is mediated by
      both proteoglycans and RAP-sensitive receptors.

PMID- 8978496
TI  - Quantitation of individual phospholipid molecular species by UV absorption
      measurements.
AB  - To validate the utility of on-line measurements of UV absorption for the direct
      quantitation of individual phospholipid molecular species isolated by reverse
      phase HPLC, we synthesized 37 different individual molecular species of diacyl
      choline glycerophospholipids. UV absorbance response factors (integrate UV
      absorbance/nmole phospholipid) were calculated for all diacyl, alkenylacyl, and
      alkylacyl species by injecting varying amounts of the purified molecular species
      in the 2-100 nmole range and integrating the UV absorbance at 203 nm. There was
      excellent agreement between the results of the quantitation of individual
      molecular species determined by measurements of phospholipid mass in HPLC
      fractions with that based on measurements of total integrated UV absorption and
      the use of absorbance response factors. The on-line quantitation of individual
      phospholipid molecular species by UV absorption measurement should prove useful
      as an adjunct to other techniques of phospholipid quantitation, as a means to
      assist in the identification of individual molecular species in complex biologic
      mixtures, and as a stand-alone approach to phospholipid quantitation to
      facilitate studies of the metabolism of individual species particularly when
      coupled with radiolabeling techniques.

PMID- 8978497
TI  - Measurement of small high density lipoprotein subclass by an improved
      immunoblotting technique.
AB  - An improved method of immunoblotting of plasma onto agarose gel matrix containing
      antiapolipoprotein A-I is described. Fresh plasma samples were subjected to
      gradient polyacrylamide gel electrophoresis (4-25%) followed by electrotransfer
      onto agarose gel layer containing antiapolipoprotein A-I. This method was
      compared with immunoblotting onto nitrocellulose where the transfer onto agarose
      gel matrix has been shown to be more convenient, quantitative, and can be kept
      permanently. Plasma apolipoprotein A-I was found to be distributed among regions
      of varying molecular weights ranging from 43,000 to 800,000. A small size
      fraction of molecular weight range of 43,000-50,000 (small HDL) was found in
      normolipidemic and hyperlipidemic subjects. The proportion of the latter fraction
      varied considerably among subjects (range: 0.0-32%), being lower in
      normolipidemic subjects (mean +/- SEM: 11.6 +/- 1.4%), and higher in
      hyperlipidemic subjects (mean +/- SEM: 23.7 %/- 1.7%, P < 0.001). Physiological
      increase in the level of the small HDL was observed in normolipidemic subjects 4
      h after fat ingestion (difference: 5.0%, P < 0.001); moreover, the level was
      higher in normolipidemic subjects who consumed moderate amounts of alcohol (mean
      +/- SEM: 17.9 +/- 1.2%, P < 0.001) compared with normolipidemic subjects who do
      not drink alcohol at all.

PMID- 8978498
TI  - Signaling effects of alpha-thrombin and SFLLRN in rat glioma C6 cells.
AB  - Effects of thrombin on brain cells, including change of neurite outgrowth and
      astrocyte shape, are described, but the molecular mechanisms are unclear. We
      investigated the effects of human alpha-thrombin and a six amino acid thrombin
      receptor activating peptide (TRAP-6, SFLLRN) on [Ca2+]i, phosphoinositide
      hydrolysis, and protein kinase C in rat glioma C6 cells. Stimulation of C6 cells
      with both alpha-thrombin and TRAP-6 resulted in [Ca2+]i mobilization,
      [3H]Inositol phosphate response, and enhanced immunoreactivity of the protein
      kinase C (PKC) isoenzymes alpha, beta, gamma, delta, and epsilon. Results suggest
      that alpha-thrombin and TRAP-6 activate at least partially the same intracellular
      signaling pathways in rat glioma C6 cells, which is evidence for involvement of
      "tethered ligand" receptor in thrombin induced signaling in glioma C6 cells.

PMID- 8978499
TI  - Intracellular localization of heat shock mRNAs (hsc70 and hsp70) to neural cell
      bodies and processes in the control and hyperthermic rabbit brain.
AB  - Heat shock proteins are essential cellular proteins that may play important roles
      in cellular repair and/or protection. This report focuses on the expression of
      two members of the hsp70 multigene family, namely, constitutive hsc70 mRNA and
      stress-inducible hsp70 mRNA in the control and hyperthermic rabbit brain. The
      intracellular localization of these heat shock mRNAs was examined using high
      resolution nonradioactive in situ hybridization. The distribution of hsc70 mRNA
      and hsp70 mRNA was examined in (1) neuronal cell bodies and their dendritic
      processes and (2) oligodendrocytes and their cellular processes. In control
      animals, hsc70 mRNA was detected in the apical dendritic processes and cell
      bodies of cortical layer II and V neurons, CA3 and CA4 neurons, deep cerebellar
      neurons, and brainstem neurons. A time course analysis of hsc70 mRNA, after a
      physiologically relevant increase in body temperature of 2.6 degrees C, revealed
      more distal transport of this constitutive message into dendrites of these
      neuronal populations. In the same neuronal populations, basal levels of hsp70
      mRNA were observed in the cell body; however, this mRNA was not detected in
      dendritic processes in control or hyperthermic animals. After hyperthermia, hsp70
      mRNA was strongly induced in oligodendrocytes and transported to the processes of
      these glial cells. The localization of heat shock messages in the processes of
      these neural cell types could provide a mechanism for local control of synthesis
      of heat shock proteins in cellular compartments that are remote from the cell
      body.

PMID- 8978500
TI  - Genetic elevation of monoamine oxidase levels in dopaminergic PC12 cells results
      in increased free radical damage and sensitivity to MPTP.
AB  - Production of hydrogen peroxide as a by-product of the breakdown of
      catecholamines by the enzyme monoamine oxidase (MAO) has been hypothesized to
      contribute to the increased proclivity of dopaminergic neurons for oxidative
      injury. We established clonal dopaminergic PC12 cell lines which have elevated
      MAO activity levels resulting from transgenic expression of the B isoform of the
      enzyme. Both MAO-A and MAO-B have relatively equivalent affinities for dopamine,
      and since PC12 primarily express the A and not the B form of the enzyme, this
      allowed us to distinguish the transgenic MAO activity in these cells from
      endogenous using the MAO-B specific substrate PEA. Elevation of MAO activity
      levels in the MAO-B+ cells resulted in higher levels of both free radicals and
      free radical damage compared with controls. In addition, increased MAO-B levels
      within PC12 cells caused a dose-dependent increase in sensitivity to the toxin
      MPTP. Our data suggests that oxidation of catecholamines by MAO can contribute to
      free radical damage in catecholaminergic neurons and that the low MAO-B activity
      levels found endogenously in these cells likely accounts for their relative
      resistance to MPTP toxicity.

PMID- 8978501
TI  - Ex vivo astroglial-induced radial glia express in vivo markers.
AB  - Ex vivo induction of radial-like glia has been previously reported to occur
      following exposure of cerebral cortex subcultures from fetal origin to cerebral
      cortex astroglial-conditioned medium. The present report further confirms
      similarities between in vivo and ex vivo radial glia, using additional criteria:
      adhesion of primary cell dissociates to glial processes, with presumptive cell
      migration along them, punctuate labelling for laminin, and immunolabelling with
      Rat-401 antisera.

PMID- 8978502
TI  - Distinct mechanisms of neurotransmitter release from PC 12 cells exposed to lead.
AB  - Two enzymes, protein kinase C and microsomal Ca(2+)-ATPase help regulate levels
      of Ca2+ in many types of cells. Since proteins that regulate Ca2+ often influence
      sensitivity to Pb2+, we determined the possible roles played by protein kinase C
      and microsomal Ca(2+)-ATPase for the Pb(2+)-evoked release of norepinephrine
      (NOR) in PC cells. NOR release was observed at 10 microM Pb2+ when PC 12 cells
      were stimulated with inhibitors of microsomal Ca(2+)-ATPase such as thapsigargin,
      cyclopiazonic acid, or 2,5-di-(t-butyl)-hydroquinone. At 5 microM, Pb2+ evoked
      the release of NOR in PC 12 cells stimulated with activators of protein kinase C
      such as phorbol 12-myristate 13-acetate (PMA) or (-)-7-octylindolactam. NOR
      release was observed at 1 microM Pb2+ in the presence of both PMA and
      thapsigargin. Ni2+ and Cd2+ blocked NOR release stimulated by Pb2+ in the
      presence of thapsigargin but not by PMA. NOR released by thapsigargin stimulation
      was not altered in PC 12 cells depleted of protein kinase C. Two proteins found
      in vesicles, chromogranin B and secretogranin-II were released with NOR. Our
      results indicate that in PC 12 cells, PB(2+)-evokes the release of
      neurotransmitters. Furthermore, thapsigargin and PMA increase the cell's
      sensitivity to Pb2+ by different pathways.

PMID- 8978503
TI  - Endothelin-3 attenuates the cyclic GMP responses to C-type natriuretic peptide in
      cultured mouse astrocytes.
AB  - The effect of endothelin-3 (ET-3) on cyclic GMP (cGMP) responses to C-type
      natriuretic peptide (CNP) was studied in primary cultures of mouse astrocytes.
      Attenuation of CNP-stimulated cGMP formation by ET-3 was time-dependent, with
      maximum inhibition achieved at 30 min of preincubation. ET-3 suppressed cGMP
      production in response to 10 nM CNP in a dose-dependent fashion, with an IC50 of
      0.04 nM and a maximal inhibitory concentration of 1 microM, which led to a 66%
      reduction of the cGMP increment from 45.0 +/- 4.2 pmol/mg protein to 15.4 +/- 2.6
      pmol/mg protein. ET-1, ET-2, and ET-3 were equipotent in suppressing the CNP
      induced cGMP response, suggesting that this effect was mediated by ETB receptors.
      Staurosporine, Ro 31-8220, calcium-free medium, nifedipine, verapamil, lanthanum,
      thapsigargin, BAPTA, W7, calmidazolium, U-73122, neomycin, quinacrine,
      wortmannin, herbimycin-A, okadaic acid, and sodium orthovanadate failed to block
      the effect of ET-3. Cycloheximide (100 microM), however, partially but
      significantly reversed the inhibitory effect of ET-3 on CNP-induced cGMP from
      48.2 to 73.3% of the control value. The results support the premise that ET-3 and
      CNP interact within the central nervous system. The data also suggest that cGMP
      accumulation in mouse astrocytes is mediated by activation of certain kinases
      through as yet undefined mechanisms and not by protein kinase C, increased
      intracellular calcium, or other second messenger pathways such as phospholipases
      A2, C, D, tyrosine kinase, or protein phosphatases.

PMID- 8978504
TI  - Ultrastructural localization of 5-hydroxytryptamine1A receptors in the rat brain.
AB  - 5-Hydroxytryptamine1A (5-HT1A) receptors have been visualized at the electron
      microscopic level in selected areas (dorsal raphe nucleus, hippocampus, septum)
      of the rat brain using specific anti-peptide antibodies. 5-HT1A receptor
      immunoreactivity was found almost exclusively in the somatodendritic compartment
      of neurons and was very rarely observed within processes possibly belonging to
      glial cells. The immunoenzymatic reaction product was associated exclusively with
      dendritic spines in the dorsal hippocampus, whereas in the dorsal raphe nucleus
      and the septal complex, immunoreactivity was found in both dendritic processes
      and somata. Although some immunolabeling was observed within the cytoplasm of
      cell bodies, 5-HT1A receptor immunoreactivity was essentially confined to the
      plasma membrane where it was unevenly distributed. It was frequently associated
      with synapses (except in the dorsal raphe nucleus), but was also found
      extrasynaptically in both somata and dendrites. These data suggest that the
      action of serotonin via 5-HT1A receptor could occur through junctional as well as
      nonjunctional transmission.

PMID- 8978505
TI  - Generation of a monoclonal antibody to the carboxy-terminal domain of tau by
      immunization with the amino-terminal domain of the amyloid precursor protein.
AB  - A fusion protein between beta-galactosidase and the amino-terminal domain of
      amyloid precursor protein (APP) was used as an immunogen for the production of
      monoclonal antibodies. One of these antibodies, the 5D12 monoclonal antibody,
      labeled the neurofibrillary tangles (NFT) by immunohistochemistry, as well as
      isolated paired helical filaments (PHF) in electron microscopy. In immunoassay,
      the ascitic fluid produced by the 5D12 clone was demonstrated to contain a high
      titer of antibodies to heat-stable microtubule associated proteins (MAPs). By
      immunoblotting, the proteins recognized in heat-stable MAPs were found to
      correspond to tau proteins. The 5D12 antibody recognized normal tau isolated from
      rat and human brain homogenates, and PHF-tau isolated from the brain of patients
      with Alzheimer's disease (AD). By immunoblotting, the 5D12 antibody also
      recognized the full-length recombinant tau protein but not the fusion protein
      used as an immunogen. The immunoreactivity of the 5D12 antibody with tau was
      completely abolished when the half-carboxy domain of tau, containing the tubulin
      binding repeats, was removed. This study demonstrates that the use of the amino
      terminal domain of APP as an immunogen led to the generation of a monoclonal
      antibody to the half-carboxy domain of tau.

PMID- 8978506
TI  - Nerve growth factor-stimulated mitogen-activated protein kinase activity is not
      necessary for neurite outgrowth of chick dorsal root ganglion sensory and
      sympathetic neurons.
AB  - Nerve growth factor (NGF)-stimulated neurite outgrowth in the rat PC12 tumor cell
      line recently has been shown to depend on the activation of the mitogen-activated
      protein (MAP) kinase kinase 1 (MEK1) (Pang et al.: J Biol Chem 270:13585-13588,
      1995). In this study we have analyzed whether or not function of the MAP kinase
      pathway is necessary for NGF-stimulated neurite outgrowth in two subtypes of
      primary neurons derived from the embryonic chick peripheral nervous system (PNS).
      Treatment of p21ras-dependent dorsal root ganglion (DRG) sensory neurons (E9)
      with the MEK1 inhibitor PD98059 at concentrations up to 100 microM did not
      prevent NGF-stimulated neurite outgrowth. At this concentration NGF-stimulated
      tyrosine phosphorylation of MAP kinase p42 as well as MAP kinase activity both
      were decreased by approximately 80%. Essentially the same results were obtained
      with p21ras-independent sympathetic neurons (E12). We conclude that, in contrast
      to the PC12 tumor cell line, NGF-stimulated MAP kinase activity is not necessary
      for neurite outgrowth of DRG sensory and sympathetic neurons derived from the
      chick PNS.

PMID- 8978508
TI  - Modulation by neurosteroids of the in vivo (+)-[3H]SKF-10,047 binding to sigma 1
      receptors in the mouse forebrain.
AB  - Recent reports suggest an interaction between neuro-(active)steroids and sigma1
      (sigma 1) receptors, affecting biochemical parameters as well as physiological
      responses mediated by sigma 1 ligands in the rodent brain. In this study, we
      examined the modulation by neurosteroids of the haloperidol-sensitive in vivo (+)
      [3H]SKF-10,047 binding to sigma 1 sites in the mouse hippocampus and cortex.
      Progesterone (PROG; 2-40 mg/kg), pregnenolone sulfate (PREGS; 10-40 mg/kg), and
      dehydroepiandrosterone sulfate (DHEAS; 10-40 mg/kg) were administered
      systemically 10 min before the radioactive tracer. The total amount of (+)
      [3H]SKF-10,047 bound in each structure was significantly affected by PROG and
      PREGS only at the highest dose tested and was unaffected by DHEAS. However, bound
      to free (B/F) radioactivity ratios were highly significantly decreased by 30-40%
      in each structure by PROG and PREGS. DHEAS, at 40 mg/kg, induced a significant
      20% decrease in the hippocampus. Furthermore, the in vivo (+)-[3H]SKF-10,047
      binding parameters were diminished in pregnant female mice compared to non
      pregnant or male mice. These results confirm the in vitro binding results, bring
      a direct in vivo demonstration of the interaction between neurosteroids and sigma
      1 receptors, and show that physiologic modulations of the steroidal
      concentrations affect the sigma 1 systems.

PMID- 8978509
TI  - Reasonable accommodation requests in a federal setting.

PMID- 8978507
TI  - Chemokine expression in rat stab wound brain injury.
AB  - A traumatic injury to the adult mammalian central nervous system (CNS) results in
      reactive astrogliosis and the migration of hematogenous cells into the damaged
      neural tissue. Chemokines, a novel class of chemoattractant cytokines, are now
      being recognized as mediators of the inflammatory changes that occur following
      injury. The expression of MCP-1 (macrophage chemotactic peptide-1), a member of
      the beta family of chemokines, has recently been demonstrated in trauma in the
      rat brain (Berman et al.: J Immunol 156:3017-3023, 1996). Using a stab wound
      model for mechanical injury, we studied the expression of two other beta
      chemokines: RANTES (Regulated on Activation, Normal T cell Expressed and
      Secreted) and MIP-1 beta (macrophage inflammatory protein-1 beta) in the rat
      brain. The stab wound injury was characterized by widespread gliosis and
      infiltration of hematogenous cells. Immunohistochemical staining revealed the
      presence of RANTES and MIP-1 beta in the injured brain. RANTES and MIP-1 beta
      were both diffusely expressed in the necrotic tissue and were detected as early
      as 1 day post-injury (dpi). Double-labeling studies showed that MIP-1 beta, but
      not RANTES, was expressed by reactive astrocytes near the lesion site. In
      addition, MIP-1 beta staining was also detected on macrophages at the site of
      injury. The initial expression of the chemokines closely correlated with the
      appearance of inflammatory cells in the injured CNS, suggesting that RANTES and
      MIP-1 beta may play a role in the inflammatory events of traumatic brain injury.
      This study also demonstrates for the first time MIP-1 beta expression in reactive
      astrocytes following trauma to the rat CNS.

PMID- 8978510
TI  - Hepatitis A vaccine.

PMID- 8978512
TI  - Worksite barriers to the effective management of alcohol problems.
AB  - The purpose of this analysis is to describe barriers to workplace interventions
      in cases of alcohol abuse. A survey of 7255 supervisors in 114 worksites across
      seven major corporations was completed (79% responded). Information about
      barriers to intervention was elicited by 12 questions. Cluster analysis revealed
      three analytically independent classes of barriers--Organizational,
      Interpersonal, and Individual. Most managers reported encountering some barriers
      to intervention: the extent of barriers perceived was related to characteristics
      of the worksite, job, and/or the environment. Barriers were greatest for female
      managers, managers in larger worksites, and the first-line supervisors. Barriers
      were also related to the form (formal vs informal) of intervention a manager was
      willing to make. Intervention strategies must take into account differences
      between company worksites and job levels, and not assume that policies are
      equally effective throughout the corporation.

PMID- 8978511
TI  - Exposure to isocyanates and organic solvents, and pulmonary-function changes in
      workers in a polyurethane molding process.
AB  - The extent of adverse health effects of isocyanates when combined with other
      chemicals is not well documented. This study was conducted as a 2.5-year follow
      up as well as to determine daily and weekly effects of exposure to isocyanates
      and organic solvents on pulmonary function. The concentrations of chemicals
      sampled were below the recommended exposure criteria. No daily or weekly
      reduction in the subjects' pulmonary function was observed. The
      isocyanate/solvent-exposed subjects showed significant long-term reduction in
      their forced vital capacity (P < 0.05) and expiratory volume in 1 second (P <
      0.001). No such changes were observed in non-exposed subjects or in those exposed
      only to organic solvents. The proportion of subjects who developed respiratory
      symptoms in the isocyanate-exposed group was not significantly greater than that
      of the non-exposed group. The results of this study indicate that long-term
      exposure to isocyanates, even in very low concentrations, may contribute to
      impaired pulmonary function.

PMID- 8978513
TI  - Biological monitoring of exposure to cadmium, a human carcinogen, as a result of
      active and passive smoking.
AB  - Cadmium (Cd), a known human carcinogen, is one of the components of tobacco and
      also has many industrial uses. Smoking Cd-contaminated cigarettes at work may
      cause an increase in blood levels and toxicity of Cd. For a population of
      nonexposed workers, we compared blood Cd and urine cotinine (Cot) levels as
      biological markers of exposure to cigarette smoke of active smokers (AS) and
      passive smokers (PS) with those of unexposed nonsmokers (UNS) in 158 workers. The
      mean Cd in AS (0.097 microgram%; ie, 0.097 microgram/100 mL whole blood) was
      significantly higher than in UNS (0.085 microgram%), and was very close to the
      mean Cd levels in PS (0.093 microgram%). Mean Cd levels in exposed past smokers
      (0.105 microgram% was higher than in nonexposed past smokers (P < 0.05) and in
      AS. The mean Cot level was significantly higher in AS than in PS or in UNS.
      Increased smoking was associated directly with increased blood Cd and urine Cot.
      Our results supported and proved quantitatively that exposure to cigarette smoke
      is harmful to both AS and PS, as we show that in both cases there is an increase
      in blood Cd. According to our results, exposure to cigarette smoke via active and
      passive smoking increases blood Cd by an average of 0.01 micrograms% over the
      background (UNS). We conclude that exposure to cigarette smoke is a confounder to
      be taken into account when carrying out epidemiological studies and surveillance
      programs on workers exposed to Cd at work.

PMID- 8978514
TI  - Airway reactivity in welders: a controlled prospective cohort study.
AB  - In a 3-year survey, respiratory symptoms, spirometry, and methacholine reactivity
      were measured annually in welders (n = 51) and non-welder controls subjects (n =
      54) to determine whether welding-related symptoms are associated with accelerated
      decline in lung function or changes in airway reactivity. In the cross-workshift
      study, maximal midexpiratory flow rate declined reversibly during a welding day,
      whereas 1-second forced expiratory volume and forced-vital capacity were
      unchanged. In the longitudinal study, the welders had significantly more
      reversible work-related symptoms of cough, phlegm, wheeze, and chest tightness
      than the non-welder shipyard control subjects. In this group of actively working
      welders, across-workshift changes in midflow and reversible symptoms were related
      to the welding occupation, but evidence for chronic irreversible effects on
      spirometry or airway reactivity was not seen over the 3 years of observation. The
      short period of observation was not optimal for detecting a chronic effect on
      lung function. Work practices and engineering controls may be successfully
      preventing irreversible respiratory effects, but not mild reversible effects, in
      this group of welders.

PMID- 8978515
TI  - Bladder cancer incidence in arylamine workers.
AB  - Cancer incidence was investigated in a cohort of 700 workers employed at a
      Connecticut chemical plant between mid-1965 and 1989. The plant produced a
      variety of chemicals, including arylamines such as dichlorobenzidine (DCB), o
      dianisidine, o-tolidine, but not benzidine. Benzidine production ceased prior to
      mid-1965. The principal finding was a statistically significant increase in the
      standardized incidence ratio (SIR) for bladder cancer in men (SIR = 8.3;
      confidence interval, 3.3 to 17.0). Based on an exposure classification system
      developed by a panel of former and current employees, the observed association
      between bladder cancer cases and exposure to arylamines increased with increasing
      exposure (SIRs = 0.0, 5.5, 16.4, for none, low, or moderate levels of exposure,
      respectively). Smoking probably contributed to the bladder cancer risk, as all
      case subjects were known to be current or former cigarette smokers.

PMID- 8978516
TI  - Liver enzyme activity and body mass index.
AB  - Obesity has been identified as a risk factor for liver disease in a number of
      cross-sectional studies. We investigated the association of biochemical livers
      tests (BLTs) among male employees of The Dow Chemical Company who had
      participated in two consecutive health surveillance examinations. The activity of
      three liver enzymes-alanine aminotransferase, aspartate aminotransferase, and
      gamma glutamyl transferase were used as measures of liver injury. Body mass index
      was strongly associated with increased enzyme activity in both examinations.
      Alcohol consumption was similarly associated with higher BLT results. Body mass
      index remained significantly associated with each BLT after controlling for
      alcohol consumption, race, and age. When changes in BLTs were investigated over
      time, the employees who gained weight showed a significant increase in alanine
      aminotransferase activity compared with those who did not gain weight.

PMID- 8978517
TI  - Lung cancer in chromate-exposed aerospace workers.
AB  - A retrospective cohort study evaluated the risk of lung cancer in aerospace
      workers with minimum of 6 months' employment in jobs with chromium [VI] exposure
      (n = 2429). Standardized incidence ratios (SIR) estimated the risk of lung cancer
      by duration of employment in chromate-exposure jobs and cumulative exposure based
      on industrial hygiene and work-history data. The overall SIR for lung cancer was
      0.8 (observed [Obs] = 15). Lung cancer risk was inversely related to estimates of
      cumulative chromate exposure and duration of employment as a painter. Although
      based on few cases, an elevated lung cancer risk was found in subjects who had
      worked for 5 or more years as a chrome plater or surface processor tank tender
      (Obs = 2, SIR = 1.9) and sander/masker or polisher (Obs = 3, SIR = 2.7). A clear
      association was not observed between chromate exposure and the risk of lung
      cancer in this population of workers.

PMID- 8978518
TI  - Evaluation of the utility of spirometry in a regional public health screening
      program for workers exposed to welding fumes.
AB  - The objective of this study was to determine the usefulness of spirometry in the
      screening of chronic pulmonary problems related to exposure to welding fumes, in
      a regional public health-based screening program. Pulmonary questionnaires and
      spirometric tests were administered twice at 5-year intervals on 229
      welders/cutters (mean age, 39.9 years from 31 metal manufacturing plants. The
      baseline mean value at the first test for the forced expiratory volume in one
      second (FEV1) was 102% of predicted, the forced vital capacity (FVC) was 107%,
      and the FEV1/FVC ratio was 79%. The mean annual changes in the three spirometric
      indicators were -47 mL, -46 mL, and -0.3%, respectively. The usefulness of
      spirometry was assessed by looking at the relationship between exposure to
      welding fumes and changes in spirometric indices, in multivariate linear
      regression analysis, accounting for age, height, and smoking. A high lifetime
      exposure to welding fumes was associated with better lung functions in the cross
      sectional approach (healthy worker effect) but not in the longitudinal approach,
      where no association was found. We concluded that the public health regional
      application of this screening program generated too many sources of variation for
      spirometry to fulfill the objective of early detection of pulmonary function
      decline related to exposure to welding fumes. Based on these observations, we
      recommend that maintaining questionnaire screening, with spirometry reserved as a
      second-line diagnostic intervention.

PMID- 8978520
TI  - Introduction: Implicit Memory, Part 2

PMID- 8978519
TI  - A prospective study for upper-extremity cumulative trauma disorders of workers in
      aircraft manufacturing.
AB  - Occupational diseases affect 15 to 20% of all Americans. Cumulative trauma
      disorders (CTDs) account for 56% of all occupational injuries. The recognition
      and control of occupational injuries has become a major concern of employees,
      employers, medicine, and the federal government because of health risk and
      related costs. Upper-extremity CTDs are identified by the National Institute for
      Occupational Safety and Health as one of the ten most significant occupational
      health problems in the United States. It is estimated by the year 2000 that 50
      cents on the dollar will be spent on CTDs. Although enlightened aircraft
      employers have developed primary prevention strategies, primary prevention can
      never be expected to eliminate 100% of the cases. To evaluate several preventive
      activities, a CTD risk-assessment program was developed and implemented in
      cooperation with a major aircraft manufacturer employing over 8000 workers. This
      program was focused on objectively identifying the relationship of work and other
      activities to an individual worker experiencing CTDs. Early identification has
      been linked, when applicable, to intervention algorithms for medical care, job
      task modification, workplace accommodation, and training. A prospective study
      group of 212 workers who used rivet guns was placed into a four-way experimental
      design for ergonomic posture training, exercise training, and rivet-gun type
      (primary factors). A statistical model was developed for the level of CTD risk
      and evaluated using the SAS software program (SAS Institute, Inc, Carry, NC).
      Statistical analysis of the primary factors without regard to associated
      variables (covariates) demonstrated that only posture training had a beneficial
      risk reduction for the individual. The impact (beneficial or detrimental) for
      exercise training and for vibration-dampening rivet guns was probably obscured
      because of the large variability of the responses regarding the associated
      variables (covariates). When the covariates were analyzed in conjunction with the
      four experimental groups, a positive benefit from ergonomic posture training and
      exercise training was demonstrated for the following groups: the dominant han,
      time spend in an awkward position, number of standard rivets bucked, number of
      parts routed, number of parts ground, number of vibration-dampening rivets
      bucked, and newly hired individuals. A negative effect (increase in individual
      risk level) for current employees using a vibration-dampening rivet gun was
      demonstrated. This prospective study helps to identify the possible benefit of
      education and training for controlling CTDs and demonstrates the usefulness of
      being able to evaluate materials, methods, machines, and environments as they
      relate to the individual's risk level for the development of upper-extremity
      CTDs.

PMID- 8978521
TI  - Medico-Psychological Study of a Memory Disorder

PMID- 8978522
TI  - Korsakoff and Amnesia

PMID- 8978523
TI  - Reactivating a Reactivation Theory of Implicit Memory
AB  - Implicit and explicit memory tasks are interpreted within a traditional memory
      theory that distinguishes associations between different classes of memory units
      (sensory features, logogens, imagens, concepts, context tags). Associations from
      specific sensory features to logogens are strengthened by perceptual experiences,
      leading to specific perceptual priming. Associations among concepts are
      strengthened by use, leading to specific conceptual priming. Activating
      associations from concepts to logogens leads to semantic and associative priming.
      Item presentation also establishes a new association from it to a representation
      of the personal context, comprising an "episodic memory." Such contextual
      associations play a major role in explicit memory tasks such as recall or
      recognition. A critical assumption of the theory is that presentation of a given
      item strengthens its sensory and contextual associations independently; this
      permits the theory to explain various dissociations of implicit and explicit
      memory measures. Furthermore, by assuming that brain-injured patients with global
      amnesia have a selective deficit in establishing novel associations to the
      context, the theory can explain their deficits in explicit memory along side
      their intact implicit memory.

PMID- 8978524
TI  - How Priming Affects Two Speeded Implicit Tests of Remembering: Naming Colors
      versus Reading Words
AB  - Three experiments investigated two timed implicit tests of memory-word reading
      and color naming. Using the study-test procedure, Experiments 1 and 2 showed that
      studied words caused reliable facilitation in word reading but no interference in
      color naming relative to unstudied words. Indeed, there was a small amount of
      facilitation in color naming as well. Experiment 3 further explored the color
      naming task by alternating shorter study and test intervals and adding control
      trials consisting of letter strings. Although both studied and unstudied words
      showed interference relative to the control letter strings, the amounts of
      interference they showed did not differ. Overall, word reading consistently
      displayed facilitation whereas color naming never exhibited increased
      interference due to word priming. Priming appears to be process-specific: It is
      restricted to facilitating repetition of processing previously applied to a
      stimulus and does not extend to influencing performance on a different task
      involving the same studied materials.

PMID- 8978525
TI  - Nonverbal Local Context Cues Explicit but Not Implicit Memory
AB  - Memory research distinguishes two components of episodes-the event or item and
      the spatial-temporal setting or context in which it occurred. The word context is
      used either globally to denote the physical, social, or emotional environment at
      study and test or it is used locally to refer to another word or picture that was
      paired with a particular target. In this article, we report four experiments that
      investigated the influence of two different nonverbal local contexts on explicit
      word recognition and implicit word identification test performance. In each
      experiment, university students studied words that were displayed against various
      extra-item local contexts, and the contexts were either the same or different at
      study and test. What differed across experiments was the nature of the contexts:
      for Experiments 1 and 2, it was a band of color that stretched across the
      computer screen, and for Experiments 3 and 4, the context was a colored line
      drawing. The combined findings from all experiments provide no evidence of memory
      context effects (MCE) on priming. By contrast, recognition test performance
      showed reliable MCEs but only when the local context was a concrete drawing or
      when it was a color that was target-related or appropriate. The discussion
      compared these findings with those from previous studies that concerned the
      cueing effectiveness of verbal and nonverbal extra-item contexts.

PMID- 8978526
TI  - Automatic Retrieval of New Associations under Shallow Encoding Conditions
AB  - In two experiments during the study phase participants read unrelated context
      target word pairs presented below a line drawing of the context word. During test
      the strong cue group was presented with context words, line drawings, and stems
      of target words. The line drawings were not presented in the weak cue group.
      Stems were paired with the same context words as at study (intact), paired with
      different context words (recombined), or corresponded to unstudied words
      (control). In Experiment 1 participants were instructed to complete stems with
      the first word that came to mind (indirect). The priming effect for new
      associations was twice as large in the strong cue group. In Experiment 2 the
      process dissociation procedure was applied and participants completed stems with
      studied words (inclusion) or with unstudied words (exclusion). Results indicated
      that consciously controlled and automatic retrieval processes mediated the
      associative effect in both groups.

PMID- 8978527
TI  - Noncriterial Recollection: Familiarity as Automatic, Irrelevant Recollection
AB  - Recollection is sometimes automatic in that details of a prior encounter with an
      item come to mind although those details are irrelevant to a current task. For
      example, when asked about the size of the type in which an item was earlier
      presented, one might automatically recollect the location in which it was
      presented. We used the process dissociation procedure to show that such
      noncriterial recollection can function as familiarity-its effects were
      independent of intended recollection.

PMID- 8978528
TI  - Levels-of-Processing Effects on a Variety of Memory Tasks: New Findings and
      Theoretical Implications
AB  - Three experiments investigated level of processing (LOP) effects on a variety of
      direct and indirect memory tasks, in the context of a processing theory of
      dissociations. Subjects studied words in five encoding conditions and received
      one of ten memory tests. In Experiment 1, four tests previously classified as
      conceptual showed a robust LOP effect, as did a direct perceptual test of
      graphemic cued recall. An indirect perceptual word fragment completion test was
      unaffected by LOP. Experiment 2 showed that a new indirect version of a graphemic
      cued test was not affected by LOP. In Experiment 3, guided by a
      generation/recognition model, we constructed three new direct tests in which
      subjects identified words that were graphemically, phonologically, or
      semantically similar to studied words. The three tests differed in their
      sensitivity to study conditions, but LOP had no effect in any case, despite the
      involvement of deliberate conscious recollection. Contemporary explanatory
      frameworks couched as dichotomies (e.g., implicit/explicit,
      perceptual/conceptual) do not provide an adequate account of the results. It
      seems necessary instead to specify the types of information activated by each
      encoding condition, the types of information required by each test, and how
      encoding and retrieval processes are modified by task instructions.

PMID- 8978529
TI  - Manipulation of Attention at Study Affects an Explicit but Not an Implicit Test
      of Memory
AB  - We investigated the impact of attention during encoding on later retrieval.
      During study, participants read some words aloud (ignoring the print color) and
      named the print color of other words aloud (ignoring the word). Then one of two
      memory tests was administered. The explicit test-recognition-required conscious
      recollection of whether a word was studied. Previously read words were recognized
      more accurately than were previously color named words. This contrasted sharply
      with performance on the implicit test-repetition priming in lexical decision.
      Here, words that were color named during study showed priming equivalent to words
      that were read during study; both were responded to faster than unstudied words.
      Thus, an attentional manipulation during study had a strong effect on an explicit
      test of memory, but almost no effect on an implicit test. Focal attention during
      study is crucial for remembering consciously but not necessarily for remembering
      without awareness.

PMID- 8978530
TI  - Continuing Influences of To-Be-Forgotten Information
AB  - In the present paper, we first argue that it is critical for humans to forget;
      that is, to have some means of preventing out-of-date information from
      interfering with the recall of current information. We then argue that the
      primary means of accomplishing such adaptive updating of human memory is
      retrieval inhibition: Information that is rendered out of date by new learning
      becomes less retrievable, but remains at essentially full strength in memory as
      indexed by other measures, such as recognition and word-fragment completion. We
      conclude with a speculation that certain unconscious influences of prior events
      may, in fact, be stronger if those events were to be forgotten rather than to be
      remembered.

PMID- 8978531
TI  - Unconscious Gender Bias in Fame Judgments?
AB  - In two experiments the conditions of, and the processes leading to, gender biases
      in fame judgments were investigated. In Experiment 1, the gender bias was not
      reduced in a condition that alerted participants to the gender of the names. In
      Experiment 2, participants' sex-role orientation, but not their gender, was
      related to the gender bias. The process dissociation procedure was used in both
      experiments in an attempt to separate conscious and unconscious memory processes
      contributing to the gender bias. Using L. L. Jacoby's (1991) original measurement
      model there appeared to be evidence for unconscious influences on the gender bias
      in fame judgments. Unfortunately, this evidence disappeared when a model was used
      that takes guessing and, hence, response biases into account, which confirms that
      measurement models that ignore response biases in the process dissociation
      procedure may lead to erroneous conclusions.

PMID- 8978532
TI  - Modeling Unconscious Gender Bias in Fame Judgments: Finding the Proper Branch of
      the Correct (Multinomial) Tree
AB  - In the preceding article, Buchner and Wippich used a guessing-corrected,
      multinomial process-dissociation analysis to test whether a gender bias in fame
      judgments reported by Banaji and Greenwald (Journal of Personality and Social
      Psychology, 1995, 68, 181-198) was unconscious. In their two experiments, Buchner
      and Wippich found no evidence for unconscious mediation of this gender bias.
      Their conclusion can be questioned by noting that (a) the gender difference in
      familiarity of previously seen names that Buchner and Wippich modeled was
      different from the gender difference in criterion for fame judgments reported by
      Banaji and Greenwald, (b) the assumptions of Buchner and Wippich's multinomial
      model excluded processes that are plausibly involved in the fame judgment task,
      and (c) the constructs of Buchner and Wippich's model that corresponded most
      closely to Banaji and Greenwald's gender-bias interpretation were formulated so
      as to preclude the possibility of modeling that interpretation. Perhaps a more
      complex multinomial model can model the Banaji and Greenwald interpretation.

PMID- 8978533
TI  - Investigating Fame Judgments: On the Generality of Hypotheses, Conclusions, and
      Measurement Models
AB  - In this article, we try to clarify some of the issues raised by S. C. Draine, A.
      G. Greenwald, and M. R. Banaji (1996) concerning our investigation into the
      gender bias in fame judgments (A. Buchner & W. Wippich, 1996). First, we did not
      test the general hypothesis and did not draw the general conclusion that Drain et
      al. suggest we did. Second, we did not reject M. R. Banaji and A. G. Greenwald's
      (1995) assumptions about the familiarity of male and female names in the fame
      judgment task, but we showed how one could have come to reject it using a
      widespread measurement model for the process dissociation procedure. Third, we
      argue that the processes which Draine et al. suggest should also be included in
      the measurement model we used are probably negligible, and if they are not, then
      the validity of the results of a number of fame judgment experiments must be
      called into question. In general, however, we agree with what seems to be the
      main message ofM. R. Banaji and A. G. Greenwald's (1995) research, namely, that
      social categories have to be considered whenever priming is investigated within a
      social domain.

PMID- 8978534
TI  - Response Bias Correction in the Process Dissociation Procedure: Approaches,
      Assumptions, and Evaluation
AB  - Buchner, Erdfelder, and Vaterrodt-Plunnecke (1995) advocated an exposition of the
      process dissociation procedure within the framework of multinomial modeling.
      Among the misleading aspects of this exposition is its tendency to obscure the
      overlap between processes. In contrast, clarifying these crucial interactions
      leads to a general classification of response bias corrections to the process
      dissociation procedure. This scheme, in which corrective models are classified on
      the basis of process interactions, clarifies the assumptions underlying
      previously proposed corrections. As an illustration of the framework, three such
      corrections are derived. These corrective models are evaluated by applying them
      to the data reported by Buchner et al. (1995).

PMID- 8978535
TI  - Can We Resolve Contradictions between Process Dissociation Models?
AB  - Wainwright and Reingold (1996) presented equations for various versions of the
      process dissociation procedure that has been used to separate conscious and
      unconscious memory processes. In the present reply it is suggested that these
      equations, though helpful, may not capture some of the key theoretical
      possibilities that could help to resolve apparent contradictions and paradoxes in
      the empirical literature. Specifically, there could be an independence of
      processes that might be estimated to a sufficient degree of accuracy for some
      theoretical purposes despite a violation of the assumption of stochastic
      independence.

PMID- 8978536
TI  - A Refined Approach to Bubble Nucleation and Polymer Foaming Process: Dissolved
      Gas and Cluster Size Effects
AB  - A refined approach to bubble nucleation is presented and applied to polymer
      foaming process. The integral overall energy balance and the integral Clausius
      Duhem inequality are used to analyze a bubble nucleation experiment. The
      computation of long-range intermolecular potential results in expressions for
      surface tension, work, and critical work for cluster formation, as functions of
      the Hamaker constant, molecular and/or repeat unit interaction distance, molar
      fractions of each component, and cluster radius. The variation of surface tension
      with cluster size, temperature, and pressure is determined in terms of well-known
      macroscopic properties and compared with available experimental data.

PMID- 8978537
TI  - Studies of Water Adsorbed in Porous Vycor Glass
AB  - Properties of water adsorbed in porous Vycor glass and Vycor glass treated with
      hexamethyldisilazane (HMDS) have been studied by measuring NMR as a function of
      water content and temperature and observing penetration of water into the pores.
      Some of the observed properties are compared with those of methanol and ethanol.
      The NMR linewidth of water in original glass pores is proportional to the
      fraction of water in a surface monolayer on the glass. The melting point
      depression of the pore water is inversely proportional to the pore radius, and
      ice water interfacial tension is evaluated as 27.5 mN/m. When treated glass was
      immersed in water, liquid water could not penetrate the glass sample, which had
      more than 0.4/nm2 trimethylsilyl group substituted for surface hydroxyls;
      however, the alcohols could still easily penetrate the fully treated glass, which
      had 1.3/nm2 trimethylsilyl groups. Water adsorbed in weakly treated glass shows
      broadening of the NMR line; contrastingly, the alcoholic hydroxyls show narrowing
      of the lines. The freezing and melting point of pore water rise with surface
      treatments. These phenomena can be explained in terms of structure forming of
      adsorbed liquid on the surfaces and the interaction between the molecules in the
      structured layer and the subsequent layer.

PMID- 8978538
TI  - Solubilization in Colloidal Immunoclusters
AB  - Micelle-like clusters of antibody molecules were prepared by covalent attachment
      of various hydrophobic groups to the protein molecules. These colloidal clusters
      were capable of solubilizing two hydrophobic probes, while the
      solubilizate:solubilizer molar ratio was dependent on the chain length of the
      hydrophobic groups, the degree of modification, and hence, on the size of the
      colloidal clusters. By using a fluorescent solubilizate, it was demonstrated that
      the immunoclusters may have a specific recognition ability.

PMID- 8978539
TI  - Modeling the Effect of Temperature on Adsorption of Lead(II) and Zinc(II) onto
      Goethite at Constant pH
AB  - The influence of temperature and adsorbate concentration on the sorption of
      Zn(II) and Pb(II) by goethite was studied at fixed pH. Proton stoichiometry,
      measured by direct titration, was found to depend on the identity of the metal
      ion, the pH, and the temperature. For Zn(II) the proton stoichiometry ranged from
      1.55 at pH 6.5 and 10&deg;C to 1.95 at pH 7.5 and 70&deg;C, while for Pb(II) at
      pH 5.50 the value varied from 1.05 at 10&deg;C to 1.4 at 70&deg;C. Three
      adsorption models-the Langmuir two-site model, the surface precipitation model of
      Farley, Dzombak, and Morel (FDM), and the BET model-were applied to the data, and
      the fitted parameters were used to determine the enthalpy and entropy of
      adsorption. Although the models assume rather different sorption reactions, and
      therefore generate correspondingly different equilibrium constants, the estimated
      enthalpies of adsorption were all positive, between 4 and 30 kJ/mol. There was
      also fair agreement between the various estimates of the adsorption capacities.
      However, the models yield very different estimates of entropies of adsorption,
      these being positive (and generally in the range 100 to 160 J K-1 mol-1) for the
      Langmuir and BET models but negative (in the range -80 to -160 J K-1 mol-1) for
      the FDM model.

PMID- 8978540
TI  - Transfer of Oil between Emulsion Droplets
AB  - A contrast matching technique was used to determine the exchange of oils between
      emulsion droplets having different refractive indexes. Emulsions of tetradecane
      and 1-bromo tetradecane in water were made separately in a high-pressure
      homogenizer, then mixed and equilibrated at rest. It was found that droplets
      exchanged oil molecules through the continuous phase, in a process similar to
      Ostwald ripening. Emulsions of hexadecane and 1-bromo hexadecane were also mixed;
      at rest, no exchange of oil took place. These mixtures were subsequently
      recirculated in the high-pressure homogenizer. Exchange of oil occurred as a
      result of droplet coalescence in the homogenizer. Two regimes were found,
      "surfactant-poor" and "surfactant-rich." In the "surfactant-poor" regime,
      recoalescence took place at all values of the pressure used in the homogenizer.
      In the "surfactant-rich" regime, recoalescence took place only if the pressure
      was at least equal to that used originally to make the emulsion. These results
      demonstrate that the size of the emulsion droplets made in a high-pressure
      homogenizer results from a succession of fragmentation and recoalescence
      processes. Possible mechanisms preventing recoalescence are discussed.

PMID- 8978541
TI  - The Influence of Sorbitol on the Adsorption of Surfactants at the Air-Liquid
      Interface
AB  - Neutron reflection and surface tension have been used to study the adsorption of
      the nonionic surfactant monododecyl hexaethylene glycol (C12E6) and the mixed
      nonionic-anionic surfactants n-dodecyl triethylene glycol (C12E3) and Sodium
      dodecyl sulfate (SDS) at the air-liquid interface. Water and a sorbitol (d
      glucitol, CH2OH(HCOH)4CH2OH)/water mixture were selected as the solvents. The
      addition of 300 g/liter of sorbitol to an aqueous solution of C12E6 reduces the
      critical micellar concentration, cmc, from approximately 7 x 10(-5) to
      approximately 3 x 10(-5) M, and increases the surface pressure at the cmc; the
      effect on the C12E3/SDS mixture is less. Despite these changes, the pattern of
      adsorption at the air-liquid interface is essentially unaltered by the addition
      of sorbitol, and the surface tension and neutron reflectivity data are in good
      agreement. The consequences of the sorbitol addition are however seen directly in
      the structure of the C12E6 monolayer. The ethylene oxide (EO) chain is more
      extended than in water, and more displaced from the solvent, consistent with
      dehydration of the ethylene oxide group.

PMID- 8978542
TI  - Direct Spectroscopic Measurement and Theoretical Modeling of the Diffusion of a
      Single Species in a Two-Phase Unstirred System
AB  - The diffusion of 8-hydroxyquinoline from an aqueous phase into an organic phase
      and vice versa has been measured using a static transfer cell. The total change
      in concentration in either phase can be accurately predicted by considering one
      dimensional diffusion in the plane normal to the oil/water interface. It was
      found that any turbulent mixing that occurs during the initiation of the
      experiment dies out in the first few minutes. The relevance of this technique to
      the study of metal ion extraction from an aqueous phase into an organic phase is
      discussed.

PMID- 8978543
TI  - A Kinetic Study of Copper Ion Extraction by Kelex 100 at a Heptane-Water
      Interface
AB  - A study of the kinetics of Cu2+ extraction by 7-(4-ethyl-1-methyloctyl)8
      hydroxyquinoline (Kelex 100) has been undertaken in a static transfer cell, where
      the total concentration of the Cu2+-Kelex 100 complex in the organic phase is
      monitored in situ as the reaction proceeds using attenuated total internal
      reflectance spectroscopy. The temporal characteristics of the extraction of Cu2+
      from water into heptane could be accounted for using a simple one-dimensional
      diffusion model coupled with a reaction-limited interaction between Cu2+ and
      Kelex 100. Rate constants for the reaction of Kelex 100 and Cu2+ at a model
      interface were obtained from stopped flow experiments using a neutral micelle
      (C12E8) system. These rate constants were used to model the reaction between Cu2+
      and Kelex 100 at the heptane-water interface.

PMID- 8978544
TI  - The ac and dc Conductivities of a Disperse System of the "Conductor-in-Conductor"
      Type
AB  - The relationship is derived, within the scope of irreversible thermodynamics, to
      predict the dc conductivity of a disperse system of the "conductor-in-conductor"
      type. The results enable one to describe the dc conductivity of the system with
      the help of the preliminary known expression for the ac conductivity as a
      function of the specific conductivities of the constituent phases. The derived
      relationship is used to study the systems with various types of morphology. It is
      discussed how the difference between the ac and dc conductivities depends on the
      system morphology and transport characteristics of both the connected and the
      disconnected constituent phases. Some ways of using the results are suggested.

PMID- 8978545
TI  - The Effect of the zeta Potential on the Stability of a Non-Polar Oil-in-Water
      Emulsion
AB  - The aim of this work was to investigate the electrophoretic properties of
      emulsion droplets of aliphatic hydrocarbons containing C6 to C16 carbon atoms in
      hydrocarbon chains. As it was observed experimentally, the emulsion droplets of
      hydrocarbons C9 to C16 revealed a completely different course of changes of the
      zeta potential due to pH than the n-alkanes of shorter hydrocarbon chains (C6 to
      C8). They revealed a negative value of the zeta potential, lower by almost twice.
      The zeta potentials of emulsion droplets of the n-alkanes, from n-nonane to n
      hexadecane, do not practically depend on the length of the hydrocarbon chain but,
      first of all, on the pH of aqueous solutions. The cause of the origin of the
      negative zeta potential of n-alkane droplets lies in the selective adsorption of 
      OH ions, causing the gathering of the excessive negative charge at the oil-water
      interface. As it was assumed, the stability of oil-in-water emulsion droplets in
      the solution, i.e., the time of collection of liquid hydrocarbons C6H28 on the
      surface of aqueous solutions, is the criterion of the life of emulsion droplets
      of n-alkanes. The observations indicate a close correlation between the emulsion
      droplets stability of the tested aliphatic hydrocarbons in water and the value
      changes of the zeta potential.

PMID- 8978546
TI  - Adsorption of CaCO3 Particles on Cationic Cellulose Graft Copolymers
AB  - The behavior of small inorganic particles at the fiber/water interface has been
      analyzed from the kinetics and isotherms of adsorption of CaCO3 particles onto
      cationic fibers. The introduction of cationic moieties onto cellulosic fibers
      leads to a copolymer that can easily adsorb negatively charged particles. At
      equilibrium, the adsorption ratio of CaCO3 particles on a cationic copolymer of
      cellulose and poly(2-acryloxyethyltrimethylammonium chloride) is related closely
      to the particle size, the temperature, the agitation, and the ionic strength of
      the suspension. Kinetic models have shown that the weakly charged copolymers
      present a high-affinity-type kinetics when the CaCO3 particle average diameter is
      small (20 to 30 MUm). For an average particle diameter equal to 72 MUm, the
      kinetics corresponds to an adsorption with a lower affinity. The rate constants
      are 6.6 x 10(-12), 2.9 x 10(-12), and 1.2 x 10(-12) m3/s for particles with
      average diameters of 20, 30, and 72 MUm, respectively. We have also noted that
      the adsorption increases with agitation and reaches a plateau after 5 min. The
      ionic strength influences the electrostatic interactions between the positive
      sites of the graft and the anion of the adsorbate. Indeed a decreasing adsorption
      is observed when the ionic strength increases.

PMID- 8978547
TI  - Energetic Classification of Adsorption Isotherms
AB  - The new model describes adsorption isotherms with a two-parameter function. The
      parameters are easy and precise to calculate from the excess surface work of the
      adsorbed layer. The excess surface work is defined as the product of adsorbed
      amount and the change of the chemical potential. The differential form yields a
      minimum at the first layer. It is possible to linearize the corresponding
      integral form. The physical meanings of the two parameters are the monolayer
      capacity and the chemical potential, which is necessary for adsorption. The new
      model allows an energetic classification of adsorption phenomena of surface films
      in the energetic range from weak physisorption to chemical adsorption

PMID- 8978548
TI  - Electrochemical Studies of the Interfacial Behavior of Insulin
AB  - The interfacial behavior of insulin and chain A and chain B of insulin was
      investigated at the platinum electrode in a phosphate buffer, pH 7.0, using
      cyclic voltammetry. The enthalpy of adsorption, DeltaHADS, calculated from a
      linear van't Hoff relationship over the temperature range 299 to 333 K gave
      values of -22 &plusmn; 1, -17 &plusmn; 1, and -9 &plusmn; 1 kJ mol-1 for insulin,
      chain B and chain A, respectively. Above these temperatures denaturation of
      insulin occurs, and for all three molecules the surface adsorption measured by
      the surface charge densities showed an immediate decrease followed by a slight
      increase. The surface concentrations of insulin of 2.9 &plusmn; 0.2 mg m-2 at 299
      K and 3.2 &plusmn; 0.3 mg m-2 at the physiological temperature of 310 K agreed
      well with the calculated value determined from geometrical dimensions. Similar
      calculations from experimental surface charge densities for chain A and chain B
      indicated that a more efficient packing prevailed with the individual
      polypeptides. From a consideration of the mechanism of adsorption based on cyclic
      voltammetric measurements, an estimation of the number of carboxylate groups on
      insulin was determined to be 6 &plusmn; 2, which agrees with the known number of
      acidic residues on the protein. Similar calculations for chain A gave 2 &plusmn;
      0.4, which indicates that this peptide remains as a monomer in the phosphate
      buffer. However, the value obtained for chain B under similar experimental
      conditions was 6 &plusmn; 2, indicating that this peptide appears to dimerize in
      the phosphate buffer. Dimer formation of insulin is known to occur through
      hydrophobic interactions and four hydrogen bonds between the B chains.

PMID- 8978549
TI  - The Effects of Salts on the Lower Consolute Boundary of a Nonionic Micellar
      Solution
AB  - A molecular model based in statistical thermodynamics is used to study salt
      effects on the lower consolute boundary of the aqueous non-ionic surfactant C8E5.
      The C8E5 micelles are modeled as hard spheres interacting via a temperature
      dependent Yukawa attraction and the salt ions are modeled as positively and
      negatively charged hard spheres interacting via a Coulombic potential. The excess
      thermodynamic properties due to the Coulombic and Yukawa potentials are evaluated
      using the analytical solutions to the Ornstein-Zernike equation obtained for the
      mean spherical approximation closure. The Yukawa parameters for the micelle
      micelle attractions are determined by fitting the theoretical phase diagram for a
      pure Yukawa fluid to the experimental lower consolute boundary for a salt-free
      C8E5 micelle-water solution. Ion-solvent interactions are indirectly accounted
      for by using previously determined adjusted values for the cation size and the
      dielectric constant of the medium. We evaluate theoretical coexistence curves for
      the C8E5 micelle-salt-water mixtures in the temperature-micelle volume fraction
      and temperature-salt molarity planes. We calculate the changes in the lower
      critical solution temperature (LCST) for the C8E5 micelle-salt-water mixture as a
      function of salt concentration for the salts NaF, NaCl, NaBr, NaI, and Na2SO4 and
      compare the trends seen with experiments. When ion-solvent interactions are
      indirectly accounted for, the theory correctly predicts the salting-out trends
      exhibited by NaF, NaCl, and NaBr. For the 1:2 salt (Na2SO4), charge effects
      resulting from the higher charge on the ions play a more important role in
      salting-out than ion-solvent interactions do. The theory, however, cannot predict
      the salting-in phenomena exhibited by NaI, thus indicating that salting-in is the
      result of variations in the intermicellar attraction as a function of the salt
      type and salt concentration. The theoretical results also indicate that excluded
      volume forces resulting from the different sizes of the salt ions cannot alone
      account for the salting-in and salting-out phenomena seen in aqueous nonionic
      micellar solutions.

PMID- 8978550
TI  - Adsorption of Nonionic Surfactants on Kaolins
AB  - Adsorption of nonionic surfactant on kaolins of different origins was studied.
      The shape of the isotherm differs only slightly according to the origin of the
      kaolin, but the amount adsorbed is quite different. The relation between the
      morphology of the kaolin particles and the shape of the isotherm is not clear.
      Fluorescence studies show two different solubilization sites for adsorbed pyrene
      molecules. However, these two environments could not be correlated to the basal
      and lateral surfaces of the mineral particles.

PMID- 8978551
TI  - Mechanism of Particle Flocculation by Magnetic Seeding
AB  - Magnetic seeding flocculation of micrometer-sized particles in liquid suspensions
      is investigated. Primary forces acting on individual particles, including gravity
      and magnetic attraction, as well as van der Waals, electrostatic, magnetic
      dipole, and hydrodynamic interparticle forces, are examined and quantified. A
      mathematical statement of the overall relative velocity is developed from the net
      force acting on a particle. From this, the equation of relative motion for two
      particles in cylindrical coordinates is derived. A computer model is then used to
      solve this equation repeatedly to find the particle trajectory borderline between
      collision and noncollision, thus determining the collision efficiency and
      collision frequency. The effects of a variety of parameters on flocculation
      performance are then explored. It is found that some factors have unexpected and
      complex influences on the collision efficiency and collision frequency,
      particularly the particle size ratio and the direction of the magnetic field.

PMID- 8978552
TI  - Comparison of Solubilization of Hydrocarbons in (PEO-PPO) Diblock versus (PEO-PPO
      PEO) Triblock Copolymer Micelles
AB  - The solubilization of hydrocarbons by micelles formed of diblock and symmetric
      triblock copolymers in water are compared in the framework of a mean-field theory
      of solubilization. The block copolymers contain poly(ethylene oxide) as the
      hydrophilic block and poly(propylene oxide) as the hydrophobic block and are
      designated as EXPYEX or EWPZ (where E and P denote ethylene and propylene oxides
      and the subscripts denote the number of segments). In the presence of a variety
      of aromatic and aliphatic hydrocarbon solubilizates, the core radius, corona
      thickness, and aggregation number of the micelle and also the volume fraction of
      the hydrocarbon solubilized in the core are predicted. The calculations show that
      for identical molecular weights and block compositions, the diblock (E200P64)
      copolymer micelles have a much larger core radius, corona thickness, aggregation
      number, and volume fraction of the hydrocarbon solubilized in the core compared
      with the symmetric triblock (E100P64E100) copolymer micelles. In contrast, the
      diblock copolymer (E100P32), having the same block composition but half the
      molecular weight of the symmetric triblock copolymer (E100P64E100), gives rise to
      micelles having the same core radius, corona thickness, and volume fraction of
      the hydrocarbon solubilized as the micelles formed of the triblock copolymer, and
      an aggregation number twice that of the triblock copolymer micelle.

PMID- 8978553
TI  - Monodisperse Electrosprays of Low Electric Conductivity Liquids in the Cone-Jet
      Mode
AB  - An experimental investigation was performed on electrosprays of low electric
      conductivity liquids (heptane with different amounts of an antistatic additive)
      that were operated in the cone-jet mode. The effects of liquid flow rate, applied
      voltage, and liquid electric conductivity on droplet size and spray
      monodispersity were systematically investigated. The droplet size was found to be
      dominantly controlled by the liquid flow rate and secondarily by the applied
      voltage. It showed no dependence on capillary size. For a given liquid, stable
      and monodisperse electrosprays could be established only within certain ranges of
      liquid flow rates and applied voltages, that defined a cone-jet domain. This
      domain was affected by the electric conductivity of the liquid. As the liquid
      electric conductivity increased, the domain shifted toward smaller flow rates
      which implies that smaller droplets were generated in the spray. An increase in
      the capillary diameter caused a narrowing of this domain. Outside the cone-jet
      domain, electrosprays were unstable and polydisperse with different instability
      patterns that depended on the applied voltage and the liquid flow rate.
      Experiments also showed that the droplet size and the spray monodispersity were
      independent of the electrode configuration, as long as the electrospray was
      operated at the onset voltage condition, that is defined as the minimum voltage
      at which the cone-jet mode was established. By using dimensional analysis the
      controlling variables were combined into a few dimensionless groups and an
      empirical fit was derived and was shown to correlate well all the experimental
      data.

PMID- 8978554
TI  - Contact Angle Studies of Ethyl Xanthate Coated Galena Particles
AB  - The wettability of ethyl xanthate coated galena particles has been determined
      from measurements of the equilibrium capillary pressure across a packed bed. Both
      the advancing liquid powder contact angle, thetap, and the specific wettable
      surface area, Awet, of galena particles have been obtained. The influence of
      particle size and ethyl xanthate surface coverage on the powder contact angle
      have been investigated and compared with floatability. Ethyl xanthate at a
      surface coverage of less than ten percent of an equivalent monolayer
      significantly increases both thetap and particle floatability.

PMID- 8978555
TI  - Optimization of Long-Term Stability of Magnetic Fluids from Magnetite and
      Synthetic Polyelectrolytes
AB  - Nanometer-sized suspensions of magnetite (Fe3O4) stabilized with polymeric
      surfactants, principally poly(methacrylic acid) (PMAA), were prepared by
      precipitation or sonication and studied by a variety of techniques. The long-term
      stability of the ferrofluids made with PMAA was optimal at pH 7 (close to the
      measured isoelectric point of the magnetite, 5.9) and improved at all pH values
      with increasing surfactant concentration. With extended times of sonication the
      molecular weight and polydispersity of the PMAA decreased, although magnetite in
      the ferrofluid was not oxidized (X-ray). Particle diameters of 9-38 nm were
      measured by saturation magnetization, electron microscopy, and dynamic light
      scattering. Centrifugation at 8,000 rpm removed the magnetite from the
      suspensions together with roughly one molecule of PMAA for each magnetite
      particle in the fluid, with the average number increasing with higher
      concentrations and average molecular weights of the polymer.

PMID- 8978556
TI  - Effect of NaCl on Aggregation Number, Microviscosity, and Cmc of N-Dodecanoyl
      Amino Acid Surfactant Micelles
AB  - Microviscosity, micellar aggregation number (N), and critical micelle
      concentration (cmc) were determined in solutions of sodium N-dodecanoyl-glycinate
      (Lau-Gly), -valinate (Lau-Val), -leucinate (Lau-Leu), and -phenylalaninate (Lau
      Phe) as a function of NaCl using fluorescent probes (auramine, pyrene). The
      microviscosity increased with increasing concentration of NaCl and reached a
      saturated value. In addition, two breakpoints were found on the curve of
      microviscosity vs NaCl concentration and by comparison with the data of N and
      solution viscosity. The first and second breakpoints were explained,
      respectively, as the beginnings of micellar growth and intermicellar interaction.
      The value of N increased steeply above the first breakpoint and the solution
      viscosity began to increase at the second breakpoint. The NaCl concentrations at
      the first and second breakpoints increased in the order Lau-Phe < Lau-Leu < Lau
      Val approximately Lau-Gly. The absolute value of the slope of the Corrin-Harkins
      plot of the cmc was smaller for Lau-Leu and -Phe than for Lau-Gly and -Val.
      Larger absolute values of the slope (1.2 approximately 2), which suggested the
      contribution of a salting out effect on cmc, were observed at high NaCl
      concentration for Lau-Gly and -Val. The micellar growth and intermicellar
      interaction occurred at lower NaCl concentration with increased size of the amino
      acid residue when the amino acid of the amino acid surfactant was larger than
      valine; that is, the hydrophobicity of the amino acid residue was the dominant
      factor rather than steric hindrance.

PMID- 8978557
TI  - Zeta Potential Measurements on Three Clays from Turkey and Effects of Clays on
      Coal Flotation
AB  - There is a growing trend of characterizing coal and coal wastes in order to study
      the effect of clays present in them during coal washing. Coarse wastes from the
      Zonguldak Coal Washery, Turkey, were characterized and found to contain
      kaolinite, illite, and chlorite. These three clays, obtained in almost pure form
      from various locations in Turkey, have been subjected to X-ray diffraction (XRD)
      analysis to assess their purity and zeta potential measurements in order to
      evaluate their properties in terms of their surface charge and point of zero
      charge (pzc) values. It was found from XRD data that these clays were almost pure
      and their electrokinetic potential should therefore be representative of their
      colloidal behavior. All three clay minerals were negatively charged over the
      range from pH 2.5 to 11. Chlorite and illite have pzc at pH 3 and pH 2.5,
      respectively, whereas kaolinite has no pzc. The effect of these clays in
      Zonguldak coal, wastes, and black waters on coal flotation was studied by
      floating artificial mixtures of Zonguldak clean coal (4.5% ash) and individual
      clay. The flotation tests on coal/individual clay revealed that each clay
      influences coal flotation differently according to its type and amount. Illite
      had the worst effect on coal floated, followed by chlorite and kaolinite. The
      loss of yield in coal was found to be 18% for kaolinite, 20% for chlorite, and
      28% for illite, indicating the worst effect of illite and least for kaolinite
      during coal flotation.

PMID- 8978558
TI  - The Conductivity Confined Temperature Dependence of Water-Free Electrorheological
      Fluids
AB  - The shear stresses and the current densities of four sorts of water-free ER
      fluids, two oxidized polyacrylonitriles-based and two aluminosilicates-based,
      were investigated at elevated and reduced temperatures in order to elucidate the
      operating mechanism. The complicated relationships among the mechanical
      properties, the current density, and temperature were especially addressed. The
      Wagner model was introduced to interpret our observations, instead of the
      commonly used conductivity model. It is found that the conductivity of the
      dispersed particles determines the temperature dependence of the shear stress and
      the current density of an ER fluid. Our findings have direct implication for the
      design of industrially required ER fluids and would be significant for ER
      applications.

PMID- 8978559
TI  - Surface Tension of Aqueous Solutions of Electrolytes: Relationship with Ion
      Hydration, Oxygen Solubility, and Bubble Coalescence
AB  - The surface tension of aqueous solutions of simple inorganic electrolytes (36 in
      total) have been measured by the maximum bubble pressure method as a function of
      electrolyte concentration up to 1 M. In most cases the surface tension increased,
      however in a minority of cases, certain combinations of cations and anions had a
      negligible effect or decreased surface tension. Results were analysed in terms of
      surface tension/electrolyte concentration gradients (d(Deltagamma)/dc) and this
      parameter was found to correlate with the entropies of ion hydration, Jones-Dole
      viscosity coefficients and dissolved oxygen gradients. Calculation of Gibbs
      surface deficiencies for selected electrolytes were carried out using the raw
      surface tension data. Discussion of the surface tension/electrolyte concentration
      gradients was extended to the mechanism of inhibition of bubble coalescence by
      electrolytes. The Gibbs-Marangoni effect did not provide a satisfactory
      explanation for the inhibition of coalescence for all electrolytes and from the
      present study we suggest that dissolved gas (microbubble) gradients between
      macroscopic bubbles plays an important role in the coalescence process.

PMID- 8978560
TI  - Anomalous Adsorption of Copper(II) on Goethite
AB  - The adsorption of copper(II) onto goethite is qualitatively different from that
      of other metal-mineral systems. At pH 5.0 the adsorption isotherms are sigmoid
      rather than hyperbolic, and the corresponding graphs of C/N versus C (where C is
      concentration and N adsorption density) have distinct minima. At pH 5.5 the
      isotherms have the more usual shape. The experimental data can be fitted by a
      model in which monomeric CuOH+ and dimeric Cu2(OH)2+2 compete for surface sites,
      the dimer adsorbing more strongly to the surface. As the concentration increases
      the proportion of the dimeric species increases, which leads to enhanced
      adsorption. At pH 5.5 adsorption of the monomer is sufficiently strong that
      normal behavior is observed at low concentrations, before there is sufficient
      dimer to compete effectively for sites. Data are presented for adsorption of
      Cu(II) to goethite at pH 5.0 and pH 5.5, at temperatures between 25 and 70&deg;C.
      Adsorption is endothermic for both monomer and dimer. Enthalpies of adsorption
      range from 50 to 91 kJ mol-1, and entropies from 240 to 470 J K-1 mol-1.

PMID- 8978561
TI  - Micropolarity of Reversed Micelles: Comparison between Anionic, Cationic, and
      Nonionic Reversed Micelles
AB  - The interface polarity of benzyl-n-hexadecyldimethylammonium chloride (BHDC)
      cationic reversed micelles in benzene was studied and compared with those of the
      anionic systems of sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT) in benzene and
      hexane. The nonionic reversed micelles of the poly(oxyethylene)n dodecyl ethers
      type surfactants Brij 30 in benzene, cyclohexane, and decane and C12E5 in hexane,
      heptane, and decane were also investigated. 1-Methyl-8-oxyquinolinium betaine
      (QB) was used as optical probe. The influence of surfactant concentration and W =
      [H2O]/[surfactant] were analyzed as a function of the absorption bands shifts in
      the visible, B1, and in the UV, B2, and the absorbances ratio of these bands. At
      W = 0 the polarity sensed in the micelle interfaces of AOT-hexane and AOT-benzene
      is entirely similar while for BHDC-benzene is quite smaller. The detected
      interaction between the QB and BHDC may favor the entrance of QB into the oil
      side of the micelle interface thus sensing a less polar environment. At W >/= 10
      once the polar heads of the surfactants are completed hydrated, the anionic as
      well as the cationic surfactants show the same behavior. The polarity of Brij 30
      and C12E5 in the aliphatic hydrocarbons is comparable. However at W = 0 their
      micropolarity is higher than that of AOT-hexane, showing that the formation of
      hydrogen bond between QB and the free OH groups of these surfactants is the major
      factor affecting the microenvironment. In all the studied systems even at the
      maximum possible W, the polarity sensed by QB never reaches the value of pure
      water, that is, never reaches the bulk water phase prevailing in the micellar
      core.

PMID- 8978562
TI  - Micromechanics: A New Approach to Studying the Strength and Breakup of Flocs
AB  - Micromechanical techniques were developed to pull apart single floc particles 6
      to 40 &mu;m in size in order to measure floc strengths and fractal dimensions.
      Flocs were formed by aggregating aqueous precipitated calcium carbonate sols with
      two water-soluble polymers. The tensile strengths ranged from 20 to 200 nN and
      showed no correlation with floc sizes when plotted on logarithmic scales. Flocs
      created by the two flocculant systems were found to have fractal dimensions of
      1.8 and 2.4 based on analysis of fragment sizes. The compact flocs favored
      breakup by surface erosion, whereas flocs characterized by the lower fractal
      dimension tended to undergo large scale fragmentation. Comparison of the two
      polymeric flocculants revealed that both the fractal dimension and the tendency
      for ruptured fragments to reflocculate were sensitive to the polymer used.

PMID- 8978563
TI  - Characterization of Silylated Silicas by Inverse Gas Chromatography: Modelization
      of the Poly(dimethylsiloxane) Monomer Unit/Surface Interactions Using
      Poly(dimethylsiloxane) Oligomers as Probes
AB  - Inverse gas chromatography (IGC) at infinite dilution was used to characterize
      the fumed silica surface. The silica was modified by chemical treatment with
      either dimethyldichlorosilane or trimethylchlorosilane. To observe the silica and
      poly(dimethylsiloxane) (PDMS) interactions, we used apolar (alkanes) and polar
      probes (chloroform, benzene, tetrahydrofuran, etc.), but also model molecules of
      PDMS such as linear and cyclic oligomers of PDMS with two to five monomer units.
      It is shown that PDMS oligomers are very appropriate to discriminate the
      silylated silicas.

PMID- 8978564
TI  - Measurement of Interaction Forces between Silica and alpha-Alumina by Atomic
      Force Microscopy
AB  - Interaction forces between a silica sphere and an alpha-alumina substrate at
      various pH values were measured by atomic force microscopy (AFM). As expected, at
      pH values of 10.8 and 10.2 when the surfaces are similarly charged, a repulsive
      force was observed. On the other hand, at pH values of 5.5, 6.4, and 8.6 when the
      surfaces are oppositely charged, attractive forces were observed. Experimental
      force vs separation distance curves were found to be in good agreement with
      theoretical predictions based on electrostatic and van der Waals interactions.
      Interestingly, when the force/radius values at a particular separation distance
      were plotted against pH, the transition from an attractive to a repulsive force
      occurred at pH 9.3, which is very close to the point of zero charge (pzc) of
      alpha-alumina as determined from electrophoresis experiments. These results
      suggest that AFM force measurements can be used to estimate the pzc of materials.
      This method may be of particular significance for soluble salt minerals where
      conventional electrophoretic measurements are not possible at high ionic
      strengths. Finally, results from transmittance studies further confirmed the
      interaction between silica and alpha alumina particles in suspensions at various
      pH values as would be expected based on the results from atomic force microscopy
      measurements.

PMID- 8978565
TI  - Apparent Dipole Moments of Aerosol OT Reversed Micelles in Cyclohexane Determined
      at a Frequency of 1 MHz and at a Temperature of 298.15 K
AB  - Precise determinations of dielectric constants were carried out for Aerosol OT
      reversed micelles in cyclohexane at a frequency of 1 MHz and at a temperature of
      298.15 K for molalities of AOT from 0 to 0.04 mol kg-1. The ratio of the amount
      of water, r, to that of AOT was varied from 0 to 25 and the apparent dipole
      moments for the mixed solute (AOT + r&middot;H2O) were calculated. Discontinuous
      change in the limiting dipole moment with increasing r was found and was related
      to the characteristic of water to bind to the head group of AOT. The process of
      forming W/O microemulsion and the molecular interactions in the micellar core are
      discussed in terms of the hydration of AOT.

PMID- 8978566
TI  - Decylammonium Chloride and Cesium Perfluorooctanoate Surface Free Energy and
      Their Critical Micelle Concentration
AB  - Measurements of the surface tension of decylamine and perfluoroheptane and
      interfacial tension of water-perfluoroheptane were carried out. Measurements of
      the contact angle were also made for water, glycerol, formamide, diiodomethane,
      bromoform, and benzene on DACl and CsPFO layers formed on Teflon and on DACl and
      CsPFO pellets, as well as of zeta potential for surfactants adsorbed on latex.
      From the results obtained and the literature data the surface free energy of DACl
      and CsPFO for both tails and heads parts of their molecules, and their free
      energy of interaction through water were determined. It was shown that the free
      energy of interaction between -CH2- groups through water, determined from
      interfacial tension, is in agreement with that obtained from the relationship
      between logCMC and the number of carbon atoms in the chain of molecules of
      surfactants having the same head. It was also shown that there is agreement
      between the total free energy of interaction between molecules of surfactants
      through water and their critical micelle concentration (CMC).

PMID- 8978567
TI  - Numerical Simulation of Bubble Motion in Water
AB  - This paper presents the results of numerical simulations for bubble motion in
      water. The motion is axisymmetric and steady in the bubble's frame of reference.
      It is assumed that the liquid is quiescent except for the motion created by the
      bubble. The bubble Reynolds numbers range up to roughly 600. The results for
      clean interfaces are compared with Duineveld's experiments. The insoluble
      surfactant model is used to model the behavior of bubbles in contaminated water.
      Calculations of wake volumes are presented.

PMID- 8978568
TI  - Formation Mechanism of Monodispersed alpha-Fe2O3 Particles in Dilute FeCl3
      Solutions
AB  - Some ambiguity is still involved in the interpretation of the growth mechanism of
      monodispersed hematite (alpha-Fe2O3) particles in dilute FeCl3 solutions. Namely,
      there are two entirely different proposals on this issue, viz. aggregation of
      preformed primary particles of alpha-Fe2O3 itself and reprecipitation of the
      ionic species through dissolution of the preformed beta-FeOOH particles. In order
      to resolve this problem, the formation process was followed in detail through
      TEM, Electron Diffraction, XRD, FT-IR, and ICP spectrometry along with
      quantitative analyses on seed effects. As a result, it has been concluded that
      the nuclei of the hematite particles are initially generated with the formation
      of beta-FeOOH particles and that they are grown by deposition of the solute
      originally present in the solution phase and indirectly furnished from the beta
      FeOOH by dissolution. As the concentration of the solute is lowered by the growth
      of the hematite particles, they continue to grow with the solute provided mainly
      from the beta-FeOOH in a steady-state of the dissolution of beta-FeOOH and growth
      of alpha-Fe2O3. The basic formation mechanism is common to the ellipsoidal
      particles grown in the presence of phosphate ions and spherical particles in
      their absence.

PMID- 8978569
TI  - Analysis of Initial Protein Surface Coverage on Fouled Ultrafiltration Membranes
AB  - Internal surface coverage of protein in membranes during the initial phase of
      ultrafiltration was analyzed. Bovine serum albumin (BSA), in solutions of pH 5
      and 7 with 0.05 and 0.15 M NaCl, were ultrafiltered with 100,000-MWCO polysulfone
      membranes. Mass uptake of the membranes was determined using electron
      paramagnetic resonance spectroscopy for separate membranes for fractions of an
      hour for up to 4 h. The resulting data were compared with models for surface
      coverage. The results showed a significant amount of protein loading exists in a
      very short time of exposure during ultrafiltration. The amount of material found
      in this period was not a function of solution properties; however, solution
      properties did affect the resistance per mass for adsorbed species when the pH
      was near the isoelectric point of BSA. The modeling comparison implied that the
      entrained solute from pH 7 appeared to behave as though it was lodged in the
      ultrathin skin area of the membrane. Solute in the membrane at pH 5 and low ionic
      strength appeared to be lodged and adsorbed throughout the membrane substructure.

PMID- 8978570
TI  - Tl+/Na+ Competitive Binding at the Surface of Dodecylsulfate Micelles in Water
      Urea Mixtures
AB  - The effect of urea on the competition between Tl+ and Na+ ions to bind with the
      surface of dodecylsulfate micelles in aqueous solution has been studied by
      fluorescence techniques, employing methods based on fluorescence quenching data
      (FQD) and critical micelle concentration measurements (CMCM). The results
      obtained are interpreted in terms of selectivity coefficients K (Tl+/Na+) defined
      within the framework of the pseudophase ion-exchange formalism. It is found that
      the ion specificity observed in the absence of urea [K(Tl+/Na+) = 3.8 +/- 0.3
      (from FQD), K(Tl+/Na+) = 2.5 +/- 0.3 (from CMCM] is progressively lost in the
      presence of increasing concentrations of urea. Typically, values of K (Tl+/Na+) =
      1.4 +/- 0.2 (from FQD) and K (Tl+/Na+) = 1.2 +/- 0.2 (from CMCM) in a water-urea
      mixture at 8 M urea, were obtained. The results are discussed in terms of urea
      association to the micellar interface and changes in the characteristics of the
      external medium.

PMID- 8978571
TI  - Self-Association of Phenothiazine Drugs: Influence of the Counterion on the Mode
      of Association
AB  - The association characteristics of the phenothiazine drug trimeprazine tartrate
      in water and aqueous electrolyte solution have been examined using static and
      dynamic light scattering techniques and compared with those reported for the
      structurally related drug promethazine hydrochloride, to identify differences in
      association pattern arising from differences in the counterions of the two drugs.
      The association of trimeprazine tartrate was micellar in water and in the
      presence of added electrolyte. A progressive increase of aggregation number and
      micellar radius was observed with increase of sodium chloride concentration over
      the range 0.05 to 0.60 M NaCl. This behavior is in contrast to that of
      promethazine hydrochloride which exhibits continuous association above the
      critical concentration in electrolyte of concentrations >/=0.2 M NaCl. Moreover,
      static light scattering curves for trimeprazine tartrate showed a single
      discontinuity corresponding to the onset of micellization, whereas the
      association behavior of promethazine hydrochloride (and other phenothiazine drugs
      with chloride counterions), in water and dilute electrolyte (0.05-0.1 M NaCl), is
      complex, with discontinuities in solution properties at several critical
      concentrations. The results of this study highlight the influence of the
      counterion on the association characteristics of this class of amphiphile.

PMID- 8978572
TI  - Effects of Monovalent, Exchangeable Cations and Electrolytes on the Infrared
      Vibrations of Smectite Layers and Interlayer Water
AB  - Infrared spectroscopy was used to investigate how nuSi-O, the frequency of Si-O
      stretching, in layers of Li- and Na-montmorillonite and nu2, the frequency of H-O
      H bending, in the interlayer water were affected by increasing the concentration,
      C, of LiCl and NaCl, respectively. Oriented gels of Li- and Na-montmorillonite
      equilibrated with solutions having various values of C were obtained by using a
      miniature pressure membrane apparatus. One part of each gel was used for the
      gravimetric determination of mw/mc, the water content. The other part was
      transferred to an FTIR spectrometer where the spectrum of the gel was measured by
      attenuated total reflectance. Thus, the dependence of both nuSi-O and nu2 on
      mw/mc was determined in the same samples. The results showed that increasing C
      had little or no effect on the relation between nuSi-O and mw/mc, or on the
      relation between nu2 and mw/mc. The vibrational coupling of Si-O stretching in
      the montmorillonite layers and H-O-H bending in the interlayer water was
      demonstrated. It was essentially independent of the species of exchangeable
      cation and C. Thus neither the species of exchangeable cation nor C had any
      specific effect on the structure of the clay layers or the structure of the
      interlayer water.

PMID- 8978573
TI  - Adsorption of Glycosidic Surfactants at the Mercury Electrode
AB  - The adsorption of glycosidic surfactants from aqueous electrolyte solutions on a
      mercury electrode was studied by means of differential capacitive measurements
      (tensammetric method). The adsorption behavior of the mono- and disaccharidic
      surfactants studied is discussed in relation to their micellar properties, in
      particular their respective critical micellar concentration (CMC). With
      monosaccharidic surfactants, a broad and bell-shaped peak is observed on the
      tensammetric curves and it suggests the formation of a monolayer called
      hemimicelle at the mercury electrode. For disaccharidic compounds, the split
      capacity peak observed at concentrations above the CMC suggests the formation of
      a multilayer of micelles throughout the electrical double layer.

PMID- 8978574
TI  - Intrinsic Proton Affinity of Reactive Surface Groups of Metal (Hydr)oxides: The
      Bond Valence Principle
AB  - The proton affinity of individual surface groups has been calculated with a
      redefined version of the multi site complexation (MUSIC) model. In the new
      approach the proton affinity of an oxygen originates from the undersaturation of
      the oxygen valence. The factors valence and coordination number, which are the
      basis of Pauling's definition of bond valence, in combination with the number of
      coordinating (Me and H) ions, are dominant in determining the proton affinity.
      The neutralization of an oxygen by Me ion(s) is calculated on the basis of the
      actual bond valence, which accounts for structural details, resulting from an
      asymmetrical distribution of charge in the coordination environment. An important
      role in the new version of the MUSIC model is given to the H bonds. The model
      shows that the proton affinity is determined not only by the number of donating H
      bonds but also by the number of accepting H bonds. The proton affinity of surface
      groups and of solution complexes can be understood in one theoretical framework,
      on the basis of a different number of donating and accepting H bonds. The MUSIC
      model predicts the variation in proton affinity constants for surface groups in
      particular those with the same number of coordinating Me ions but with a
      different structural position. The model is able to predict on the basis of the
      proton affinity of the individual groups the correct PZC of Me hydroxides,
      oxohydroxides, and oxides, and explains previous exceptions. The model can also
      be applied in general to other minerals.

PMID- 8978575
TI  - Coarsening Due to Thermally Induced Marangoni Convection
AB  - The growth of closely packed droplets in a decomposing butoxyethanol/water
      mixture is studied at reduced gravity during scaled times t* = t(D/xi2) on the
      order of t* = 10(6) (t, time; D, diffusion coefficient; xi, correlation length).
      Thermally induced Marangoni convection at the surfaces of the droplets causes an
      enhancement of the coarsening process.

PMID- 8978576
TI  - Biochemical modulation: its pharmacological basis and clinical applications.
      Proceedings of a meeting. Singapore, October 19, 1995.

PMID- 8978577
TI  - A comparative, randomized trial of UFT and 5-fluorouracil in combination with
      cyclophosphamide and doxorubicin in the treatment of advanced breast cancer
      patients at The Philippines General Hospital.
AB  - A comparative, randomized trial was conducted to determine the efficacy of oral
      UFT (Tegafur and Uracil) versus 5-fluorouracil (5-FU) in combination with
      cyclophosphamide and doxorubicin in patients with metastatic breast cancer. Of 62
      evaluable patients, 31 received UFT (350 mg/m2/day orally x 14 days), doxorubicin
      (50 mg/m2 intravenously [I.V.] day 1) and cyclophosphamide (500 mg/m2 I.V. day
      1). The other 31 patients received 5-FU (500 mg/m2 I.V. days 1 and 8),
      doxorubicin (50 mg/m2 I.V. day 1), and cyclophosphamide (500 mg/m2 I.V. day 1).
      Regimens were repeated for a total of six cycles. The two groups were comparable
      in terms of age, gender, performance status, menopausal status, and number and
      sites of metastases. No statistical difference in overall response rates was seen
      (UFT arm, 48.4% vs. 5-FU arm, 35 %; p = 0.30). Median response duration was 16
      weeks (range, 4-30) for both arms. The toxicity profile (alopecia, anemia,
      leukopenia, thrombocytopenia, diarrhea) was similar in both groups and both
      regimens were well tolerated. Anemia and stomatitis were significantly more
      common in the 5-FU arm (p = 0.02). Thus, oral UFT has response rates and duration
      of response that are comparable to 5-FU in a combination regimen for advanced
      breast cancer.

PMID- 8978578
TI  - Mechanism-based improvement in the therapeutic selectivity of 5-FU prodrug alone
      and under conditions of metabolic modulation.
AB  - To compare the antitumor activity of Tegafur (150 mg/kg/day) with continuous
      intravenous infusion of 5-fluorouracil (5-FU) (12.5 mg/kg/day) and with oral UFT
      (60 mg/kg/day) with and without low- or high-dose leucovorin (50 or 200
      mg/kg/day), rats with advanced colon cancer were treated with Tegafur or UFT 3
      times daily for 28 days and 5-FU by continuous intravenous infusion for 28 days.
      UFT alone had a complete remission (CR) rate of 38%, whereas Tegafur and 5-FU
      produced no CRs. When high-dose leucovorin was added, the CR rate for UFT
      increased to 75%; Tegafur plus high-dose leucovorin resulted in only a partial
      remission rate of 50%, with no CRs; low-dose leucovorin was not as effective as
      the high dose. Hence, UFT clearly offers significant therapeutic advantages over
      Tegafur and protracted infusion of 5-FU. High-dose leucovorin is essential for
      significant modulation of drug action in this tumor.

PMID- 8978579
TI  - Clinical application of biochemical modulation in cancer chemotherapy:
      biochemical modulation for 5-FU.
AB  - The addition of Uracil to Tegafur, a prodrug of 5-fluorouracil (5-FU), has been
      shown to enhance the antineoplastic effect of 5-FU while reducing the side
      effects attributed to 5-FU catabolism. Studies of 5-FU levels have shown that the
      5-FU concentration in the tumor tissues of patients with head and neck cancer was
      16.9 times greater than that in serum and approximately 2-6 times greater than in
      normal tissue. Similar observations have been made in tumor tissues of patients
      with breast cancer. The clinical efficacy of UFT, the combination of Uracil and
      Tegafur in a molar ratio of 4:1, has been studied in a variety of tumor types. An
      overall response rate of about 23% was obtained, with responses exceeding 30% in
      patients with head and neck, breast, and bladder cancer. Side effects are
      predominantly that of gastrointestinal toxicity. Hematologic toxicity is minimal
      and hepatotoxicity is rare. The UFT combination produces a good clinical effect
      in a variety of tumor types and is well tolerated.

PMID- 8978580
TI  - Phase II study of UFT plus leucovorin in colorectal cancer.
AB  - The activity and toxicity of UFT (Tegafur and Uracil) in a 4:1 molar
      concentration, plus leucovorin (LV), were evaluated in the treatment of 45
      patients with advanced, bidimensionally measurable metastatic colorectal
      carcinoma. Initially 350 and later 300 mg/m2/day, plus 150 mg LV, as administered
      in divided doses every 8 h for 28 days. After two courses of treatment, responses
      were evaluated. The overall response rate was 42.2%, with responses observed in
      liver (n = 18), lung (n = 6), and bone (n = 1). Five of the 7 patients who
      received 350 mg/m2 UFT experienced prolonged grade 3 diarrhea, resulting in a
      dose reduction to 300 mg/m2; 9 patients in the 300-mg/m2 group experienced grade
      3 diarrhea, vomiting, abdominal cramping, and fatigue. Minor toxic effects
      included oral mucositis and rash. The oral regimen of 300 mg/m2/day UFT, plus 150
      mg/day LV, administered for 28 days appears to have significant activity against
      metastatic colorectal carcinoma. The treatment is well tolerated; neutropenia did
      not occur, and oral mucositis was not significant, even though both are
      characteristic of intravenous schedules of 5-fluorouracil plus LV. The results of
      this trial constitutes the basis of phase III clinical trials comparing this oral
      schedule with intravenous 5-FU and LV to compare clinical efficacy, impact on
      well-being, and cost. In addition, the current National Surgical Adjuvant Breast
      and Bowel Project (NSABP) adjuvant colon clinical trial (CO-6) will compare this
      28-day schedule of UFT plus oral leucovorin with a weekly regimen of intravenous
      5-fluorouracil plus leucovorin in the postoperative adjuvant therapy of Dukes' B
      and C colon cancer patients.

PMID- 8978581
TI  - UFT modulated with leucovorin in advanced colorectal cancer: Oncopaz experience.
AB  - A phase II trial of UFT (Tegafur and Uracil) modulated by leucovorin was
      undertaken by the Oncopaz Cooperative Group to assess the efficacy and toxicity
      of this combination in patients with advanced colorectal cancer. A total of 75
      patients were given 500 mg/m2 intravenous leucovorin and 195 mg/m2 of oral UFT on
      day 1, followed by oral leucovorin 15 mg/12 h and 195 mg/m2/12 h of oral UFT on
      days 2-14. An overall response rate of 39% was obtained, with seven complete
      responses (9%), and 22 partial responses (29%). The primary toxicity was
      gastrointestinal, with grade 1-2 diarrhea occurring in 8.5% of courses, and grade
      3-4 in 3.5%. Hematologic toxicity was minimal, and there were no deaths due to
      toxicity. This regimen was active and well tolerated in patients with advanced
      colorectal cancer, including those 70 years of age or older.

PMID- 8978582
TI  - Experience of Oncopaz Cooperative Group with oral fluoropyrimidines in tumors of
      the stomach, lung, head and neck, and breast.
AB  - The Oncopaz Cooperative Group designed a chemotherapy regimen to modulate UFT
      (Tegafur and Uracil) with leucovorin. The regimen consisted of a high intravenous
      dose of leucovorin, followed by oral UFT and oral leucovorin twice daily for 14
      days. Based on the promising results obtained with this regimen in patients with
      advanced colorectal cancer, the Oncopaz group performed several phase II trials
      using this combination with other drugs to treat advanced gastric, lung, head and
      neck, and breast cancers. When combined with etoposide in gastric cancer, the
      regimen was shown to be active and well tolerated. However, when used with
      cisplatin to treat non-small cell lung cancer, a low response rate and high
      toxicity precluded its recommendation for further study. The addition of
      carboplatin in the treatment of head and neck cancer demonstrated moderate
      activity with low toxicity. In an ongoing trial of advanced breast cancer,
      preliminary results indicate that the combination of idarubicin, UFT, and
      leucovorin is active, with moderate, primarily hematologic toxicity. Trials of
      new combinations are warranted to take advantage of the pharmacokinetic
      properties and oral bioavailability of UFT and leucovorin.

PMID- 8978584
TI  - Comparison of two different doses of ondansetron plus dexamethasone in the
      prophylaxis of cisplatin-induced emesis.
AB  - This study was conducted to evaluate the efficacy of two different doses of
      ondansetron (8 mg vs. 24 mg) plus dexamethasone in the prevention of cisplatin
      (CDDP)-induced emesis and nausea (acute and delayed). The persistence of the anti
      emetic efficacy during the second cycle of chemotherapy was also assessed. Eighty
      patients receiving high-dose CDDP (>80 mg/m2) were randomized to have either
      ondansetron 8 mg plus dexamethasone 20 mg (8 mg group) or ondansetron 24 mg plus
      dexamethasone 20 mg (24 mg group), given intravenously as a single dose before
      the CDDP infusion. From days 2-5, all patients received oral ondansetron 8 mg
      twice daily. Seventy-five patients (38 in the 8 mg group and 37 in the 24 mg
      group) were evaluable for analysis. Among these, there were 24 patients who
      received ifosfamide (IFO) on the 2nd day of treatment; these patients were
      evaluated separately for delayed emesis. Complete protection from acute emesis
      was obtained in 26 (68.4%) and 26 (70.3%) patients, in the two groups,
      respectively. Complete protection against acute nausea was achieved in 23 (60.5%)
      and 24 (64.9%) patients, respectively. With respect to the delayed emesis,
      complete protection was achieved in 14 (56%) and 13 (50%) patients not receiving
      IFO and in 4 (30.8%) and 3 (27.3%) of those receiving IFO. The figures for the
      delayed nausea were: 12 (48%) and 13 (50%), 2 (15.4%) and 2 (18.2%),
      respectively. Similar protection against emesis and nausea was recorded during
      the second cycle of chemotherapy. Both regimens have the same efficacy and thus,
      taking into account the cost-effectiveness, 8 mg of ondansetron plus
      dexamethasone in a single intravenous dose should be used for the prevention of
      high-dose CDDP-induced emesis.

PMID- 8978585
TI  - A randomised, double-blind, parallel-group study to compare the efficacy and
      safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus
      dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin
      chemotherapy.
AB  - A double-blind, parallel-group study in 189 ovarian cancer patients compared the
      efficacy of ondansetron 8 mg i.v. (OND) and metoclopramide 60 mg i.v. (MET) both
      in combination with dexamethasone 20 mg i.v. in the prevention of carboplatin
      induced emesis. On day 1, complete or major control of emesis (0-2 emetic
      episodes) was observed in 97% patients from the OND group compared with 74%
      patients from the MET group (p < 0.001). Similarly, a worst-day analysis over
      days 1-3 showed complete or major control of emesis in 87% patients (OND)
      compared wth 66% patients (MET) (p < 0.001). Similar findings in favour of the
      OND group were observed for nausea grade on day 1 and the worst-day grade during
      days 1-3. OND was better tolerated than MET. Fewer patients from the OND group
      (13%) reported adverse events compared with the MET group (21%). Extrapyramidal
      type symptoms were observed in 6 (6%) patients from the MET group (paraesthesia,
      involuntary movement of the jaw and tongue, and restlessness), compared with none
      from the OND group. Ondansetron plus dexamethasone is a highly effective and well
      tolerated treatment and is significantly superior to metoclopramide plus
      dexamethasone in the prevention of carboplatin-induced emesis.

PMID- 8978586
TI  - Chemotherapy-induced spontaneous pneumothorax in a patient with bulky mediastinal
      lymphoma: a rare oncologic emergency.
AB  - Chemotherapy-induced spontaneous pneumothorax (SP) has been described
      sporadically in chemosensitive tumors, particularly sarcoma, with multiple lung
      metastases. We present a patient who developed SP following rapid regression of
      bulky mediastinal lymphoma. Immediately on chest tube insertion, the lung
      recovered and further chemotherapy could be delivered uneventfully. We suggest
      that (1) chemotherapy-induced SP should be included amongst oncologic emergencies
      and that (2) a high degree of awareness of this complication is required.

PMID- 8978587
TI  - 'Spontaneous' regression of advanced leiomyosarcoma of the urinary bladder.
AB  - A case of advanced leiomyosarcoma of the urinary bladder is reported in a 25-year
      old man who, in a short time, experienced a complete 'spontaneous' regression of
      his fatal illness. He first presented with severe haemoperitoneum resulting from
      an unresectable bleeding tumour of the urinary bladder. Debulking surgery was
      performed, followed by salvage chemotherapy. Histological and ultrastructural
      examinations of the tumour confirmed a poorly differentiated leiomyosarcoma. The
      residual disease failed to respond to salvage chemotherapy, but regressed
      'spontaneously' 5 months after cessation of therapy. The patient is alive without
      evidence of disease 51 months after the diagnosis. This remarkable phenomenon and
      relatively long survival in a poor-risk leiomyosarcoma of the urinary bladder has
      never been reported previously.

PMID- 8978588
TI  - Brachytherapy for penile cancer using silicon mold.
AB  - We analyzed the treatment results of 15 patients with penile cancer treated by
      afterloading brachytherapy with a silicon-made mold we devised. The group
      included 8 patients with T1, 5 with T2 and 2 with T3 tumors, and inguinal lymph
      node metastases were noted in 4 patients. The total dose of brachytherapy ranged
      from 32 to 74 Gy with or without an electron beam boost. The median dose rate was
      200 cGy/h ranging from 100 to 350 cGy/h. Local control was achieved in 12 of the
      15 patients (80%), and was related to the T category, with 100% of T1 and 80% of
      T2, in contrast to 0% of T3 tumor. Three patients with partial response or
      residual tumor underwent amputation. Local recurrence was recognized in 1 patient
      with a T2 tumor, but salvaged by surgery. Penis conservation was achieved in 11
      of 15 patients (73%). Of the 4 patients with inguinal lymph node metastases, 3
      were controlled by surgery and radiation therapy. The other with a T3 tumor died
      from the disease. Brachytherapy with a mold for penile cancer was considered to
      be the first choice for penis-conserving therapy, and the patients with T1 and T2
      tumors have good indications for this method of treatment.

PMID- 8978589
TI  - Carboplatin as an anticancer agent for transcatheter arterial chemoembolization
      in patients with hepatocellular carcinoma.
AB  - Transcatheter arterial chemoembolization (TACE) is a conservative treatment in
      patients with hepatocellular carcinoma (HCC). In the present study, 30 patients
      with unresectable HCC underwent TACE using carboplatin (300 mg), and their
      clinical results were evaluated. After TACE, 18 (60.0%) of 30 patients
      demonstrated tumor size reduction rates > or = 50%. Of 23 patients with
      pretreatment serum alpha-fetoprotein (AFP) levels >20 ng/ml (cutoff), 14 (60.9%)
      showed AFP reduction > or = 75%. The 1-, 2-, 3- and 4-year survival rates were
      82.9, 68.1, 45.1 and 37.6%, respectively. The median survival was 2.3 years. The
      only notable adverse reaction accompanying TACE was a transient myelosuppression.
      Carboplatin is thought to be a useful anticancer agent in patients with HCC
      treated with TACE.

PMID- 8978590
TI  - Intensive chemotherapy plus recombinant human granulocyte-colony stimulating
      factor support for distant metastatic nasopharyngeal carcinoma. A preliminary
      report.
AB  - Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to
      chemotherapy. The major limiting toxicity was myelotoxicity. Recently, the role
      of granulocyte colony-stimulating factor (G-CSF) in reducing chemotherapy-induced
      neutropenic sepsis has been well established. In this study, we tested whether
      recombinant human G-CSF (rhG-CSF) could effectively support the bone marrow
      function in both previously untreated and pretreated metastatic NPC patients
      receiving intensive chemotherapy. Twelve patients with distant metastatic
      disease, 5 newly diagnosed (group A) and 7 pretreated patients (group B), were
      enrolled to receive BEC (bleomycin, epirubicin and cisplatin), followed by rhG
      CSF support (50 microg/m2 s.c. daily for 10 days) every 4 weeks for two cycles.
      Four patients in group A completed the treatment as scheduled while only 2
      patients in group B did. After the first treatment cycle, 6 patients (50%) had
      grade III-IV myelosuppression. Five of the patients were from group B. The mean
      values of the white cell count nadir were 2,680 (range 1,200-3,700) in group A
      and 1,343 (range 400-2,900) in group B (p = 0.0386). Neutropenia-associated fever
      occurred in 7 patients, 6 of whom had received previous treatment. There were 2
      deaths due to toxicity, and both patients had liver metastases within 6 months
      following radiation. After 24 months of follow-up, only 1 patient is still alive.
      Our preliminary results suggest that in previously treated metastatic NPC
      patients, bone marrow suppression is still the major limiting toxic side effect
      of aggressive chemotherapy, especially for those patients with liver recurrences
      within 6 months after irradiation and despite rhG-CSF support.

PMID- 8978591
TI  - Follow-up study in head and neck cancer: cure rate according to tumor location
      and stage.
AB  - The purpose of this clinical study was to analyze a long-term follow-up of all
      the patients with head and neck cancer in our institution. Between 1973 and 1993,
      1,355 consecutive cases of head and neck cancerwere diagnosed, treated and
      followed up regularly. All were subjected to a multidisciplinary approach, and
      followed up until death or for 10 years with no event of disease. The local
      relapse rate was 20% and the node-regional relapse rate 15%. Distant metastases
      were observed in 6% of the patients mainly arising from the nasopharynx (23%)
      followed by the hypopharynx (11%). The main organ involved was the lung (50%).
      Median follow-up of the group was 10 years (range 4 months to 15 years). Cancer
      cure was observed after 5 years in glottic and supraglottic laryngeal carcinoma,
      oral and nasopharyngeal cancer and after 2.5 years in patients with cancer of the
      oropharynx and hypopharynx. The highest cure rate was 80% in the glottis,
      followed by 70% in the supraglottic area, 45% in the mouth, 30% in the
      nasopharynx, 25% in the oropharynx, and 20% in the hypopharynx. A second primary
      tumor was observed in 7% of the patients and a third primary in 0.6% of the
      patients. Only in 7 patients, the second or third primary was seen after 5 years
      of follow-up. Curability should be observed after 5 years from definitive therapy
      of glottic, supraglottic, oral and nasopharyngeal and earlier in oropharyngeal
      and hypopharyngeal cancer. Further follow-up should be discontinued. Second and
      third neoplasias are the main problems after 5 years of follow-up but their
      incidence is low.

PMID- 8978592
TI  - CYFRA 21-1: an indicator of survival and therapeutic effect in lung cancer.
AB  - CYFRA 21-1 is a new tumor marker using two different monoclonal antibodies which
      recognize the divergent epitope on the N- or C-terminal region of domain 2 of
      cytokeratin 19 fragment, respectively. In this study, we investigated the
      relationship between levels of CYFRA 21-1 and survival duration, as well as the
      efficacy of chemotherapy associated with changes in CYFRA 21-1. Serum samples
      were obtained from 87 patients with nonoperable lung cancer (35 cases with
      squamous-cell carcinoma, 33 with adenocarcinoma, 3 with large-cell carcinoma, and
      16 with small-cell carcinoma). The cutoff point was set at 3.5 ng/ml. In a CYFRA
      21-1 assay, significantly more patients with squamous-cell carcinoma and
      adenocarcinoma were positive compared to patients with small-cell and large-cell
      carcinomas (p = 0.0017). Following chemotherapy, blood levels of CYFRA 21-1
      decreased significantly in responders versus nonresponders (p = 0.0246). A
      significant correlation was noted between survival periods and pretreatment
      levels of CYFRA 21-1 (p = 0.0036). The present study suggests that CYFRA 21-1
      might be useful as a possible indicator of survival and therapeutic effect for
      lung cancer.

PMID- 8978593
TI  - Combination effect of anti-Fas antibody and chemotherapeutic drugs in ovarian
      cancer cells in vitro.
AB  - To clarify the significance of the Fas antigen (Ag) in gynecologic tumors, its
      expression in gynecologic cancer cell lines was examined. The Fas Ag was
      expressed in 6 of 15 cell lines. Five of 8 ovarian cancer cell lines but none of
      4 choriocarcinoma cell lines expressed the Fas Ag. In drug-resistant cell lines
      derived from one of the Fas-positive cells, its expression was not lost after
      development of resistance to cisplatin, SN-38 or etoposide, but its expression
      was absent in the cell line resistant to Adriamycin. The effect of the anti-Fas
      antibody (Ab) was then studied. Apoptosis was induced in 7 of 9 Fas-positive cell
      lines, whereas the remaining two cell lines were unaffected. Furthermore, the
      combination effect of the anti-Fas Ab and drugs was examined in an ovarian cancer
      cell line and its drug-resistant variants, and a synergistic effect was observed.
      These results suggest important roles of the Fas Ag in ovarian cancer and the
      potential for overcoming drug resistance by a combination of the anti-Fas Ab and
      various drugs.

PMID- 8978594
TI  - Slow increase in intranuclear and cytosolic free calcium concentrations in L929
      cells is important in tumour necrosis factor-alpha-mediated cell death.
AB  - The potential involvement of cellular calcium in the signalling pathway of tumour
      necrosis factor-alpha (TNF) was assessed in L929 cells using 45Ca2+ and confocal
      laser scanning microscopy with fluorescence calcium indicators. Our data indicate
      that the effect of TNF on intracellular Ca2+ mobilization is a slow process with
      no discernible increase in the cytosolic free Ca2+ concentration ([Ca2+]c) and
      intranuclear Ca2+ level ([Ca2+]n) within the 1st min of TNF (25 ng/ml)
      administration. However, prolonged exposure (2 h) of L929 cells to TNF brought
      about pronounced increase in cytosolic and intranuclear [Ca2+] even in the
      absence of external Ca2+. The increase in intracellular [Ca2+] was more apparent
      when cells were treated with thapsigargin, an inhibitor of microsomal Ca2+
      ATPase. Interestingly, most of the Ca2+ released was around and confined to the
      nucleus. Following the pretreatment of cells with thapsigargin, a synergistic
      killing effect was obtained when cells were cultured with TNF. The use of 45Ca2+
      also revealed that TNF enhanced the 45Ca2+ uptake in a time-dependent manner.
      Calcium channel blockers, verapamil and diltiazem, could alleviate both the TNF
      mediated 45Ca2+-uptake and killing activity. Our results therefore suggest that
      an increase in cellular Ca2+ is a crucial factor in the TNF cytotoxicity.

PMID- 8978595
TI  - Immunohistochemical analysis of nucleoside diphosphate kinases in oral squamous
      cell carcinomas.
AB  - The nm23 gene is a potential metastasis suppressor gene originally identified
      using a murine melanoma cell line. The nm23 proteins are nucleoside diphosphate
      (NDP) kinases, and there are two isotypes in human and other mammalian cells.
      Immunohistochemical analysis with anti-rat NDP kinase (NDP kinase alpha, NDP
      kinase beta) monoclonal antibodies was performed in deparaffinized sections of 56
      specimens of oral squamous cell carcinoma. Detection of these NDP kinases in
      tissue samples was correlated with clinical and histopathological factors. The
      NDP kinase A (nm23 H1 protein)-positive group was apt to have a lower frequency
      of neck metastasis than the negative one (p < 0.01). Consequently, it is
      suggested that NDP kinase A might be a metastasis suppressor factor that may be
      useful for predicting tumor metastases in patients with oral squamous cell
      carcinoma.

PMID- 8978596
TI  - Antitumor effect of murine colon carcinoma cells retrovirally transduced with
      interleukin-4 and granulocyte macrophage-colony stimulating factor genes.
AB  - We have investigated the antitumor effect of murine colon carcinoma cells
      developed to produce cytokines. Retrovirally transduced cells were inoculated
      into syngeneic mice, and their survivals were examined. Inoculation of
      interleukin-4 (IL-4)- or granulocyte macrophage-colony stimulating factor (GM
      CSF)-producing cells alone did not affect the survival of the mice. In the tumors
      derived from an admixture of IL-4 and GM-CSF producers, however, regression
      developed spontaneously, and prolonged survival of the challenged mice was
      consequently observed. Histological examination revealed predominant infiltration
      of neutrophils around the tumor of a mixed population of IL-4 and GM-CSF
      producers.

PMID- 8978597
TI  - Effects of cisplatin on testicular tissue and the Leydig cell-pituitary axis.
AB  - The mechanisms responsible for the rapid increases in levels of gonadotropin and
      steroid hormones upon administration of cisplatin to rats are not clearly
      understood. In the present study, the morphologic effects of cisplatin on the
      testis and the relationship of these changes to serum hormone levels were studied
      in adult rats. Upon administration of a single dose (5 mg/kg) of cisplatin, the
      levels of testosterone in the peripheral blood decreased and the level of
      luteinizing hormone (LH) increased. After 3 days, significant damage to the
      germinal epithelium became detectable by morphologic examination. In Leydig and
      Sertoli cells, dilatation of the endoplasmic reticulum, structural changes in
      mitochondria and an increase in the numbers of inclusion bodies were detected.
      Although blood-testis barriers between Sertoli cells were normal, the
      relationship between germinal cells and the relationship between germinal cells
      and Sertoli cells were distorted. It is concluded that damage to Leydig cells and
      withdrawal of the controlling effects of the germinal epithelium on the LH-Leydig
      cell axis could explain the changes in serum hormone levels.

PMID- 8978598
TI  - Lysosomal cathepsins B and L and Stefin A blood levels in patients with
      hepatocellular carcinoma and/or liver cirrhosis: potential clinical implications.
AB  - The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular
      inhibitor of these proteolytic enzymes, were determined in patients with
      hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with
      some clinical and biochemical parameters of these diseases. Cathepsin B serum
      levels were increased in HCC and in LC patients as compared to normal subjects (p
      < 0.001). However no difference was observed between HCC and LC groups.
      Interestingly, a significant relationship was evidenced between cathepsin B serum
      content and the grade of severity of cirrhosis (r = 0.41; p < 0.001). Cathepsin L
      was significantly elevated only in sera of cancer patients as compared to normal
      subjects or LC patients (p < 0.001) and significantly correlated with the number
      of malignant lesions (r = 0.49; p = 0.001). Stefin A serum levels were increased
      in HCC and LC patients as compared to healthy subjects (p < 0.02). However, these
      levels were significantly higher in the LC group as compared to the HCC group (p
      < 0.05). In cancer patients, a significant relationship was observed between
      Stefin A serum content and tumor size (r = 0.35; p < 0.05), number of neoplastic
      lesions (r = 0.556; p < 0.001) and serum alpha-fetoprotein (r = 0.38; p < 0.01).
      These data suggest that cathepsin B and L and Stefin A may be potentially useful
      as additional biochemical parameters to monitor the therapeutic response of these
      diseases to clinical treatments and to identify patients with cirrhosis
      developing precancerous lesions.

PMID- 8978600
TI  - The emerging field of receptor-mediated inhibitory signaling: SHP or SHIP?

PMID- 8978599
TI  - p53 protein expression in gastrointestinal lymphomas.
AB  - We investigated the p53 protein expression in gastrointestinal lymphomas (GIL).
      Paraffin-embedded samples of 52 patients were examined for this purpose. The
      avidin-biotin Complex method was used for immunostaining. Nine of the 52 samples
      (17.3%) showed p53 staining. There was no relationship between the p53 protein
      expression and clinical characteristics, such as stage, disease localization and
      tumor burden. Complete remission was higher in patients not expressing this
      protein, and the p53 protein was more frequently expressed in intermediate and
      high grade histopathology than low grade lymphomas, but there was no
      statistically significant difference between the two groups (p = 0.008).
      Interestingly, patients expressing the p53 protein were younger than the ones not
      expressing it (30.7 +/- 14.1 vs. 43.6 +/- 15.7 years). We conclude that the p53
      protein expression in GILs may be a poor prognostic indicator due to a lower
      response rate to chemotherapy.

PMID- 8978601
TI  - Meiotic recombination in yeast: coronation of the double-strand-break repair
      model.

PMID- 8978602
TI  - Zebrafish make a big splash.

PMID- 8978603
TI  - The molecular basis of focal cyst formation in human autosomal dominant
      polycystic kidney disease type I.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common disease and an
      important cause of renal failure. It is characterized by considerable
      intrafamilial phenotypic variation and focal cyst formation. To elucidate the
      molecular basis for these observations, we have developed a novel method for
      isolating renal cystic epithelia from single cysts and have used it to show that
      individual renal cysts in ADPKD are monoclonal. Loss of heterozygosity was
      discovered within a subset of cysts for two closely linked polymorphic markers
      located within the PKD1 gene. Genetic analysis revealed that it was the normal
      haplotype that was lost. This study provides a molecular explanation for the
      focal nature of cyst formation and a probable mechanism whereby mutations cause
      disease. The high rate at which "second hits" must occur to account for the large
      number of cysts observed suggests that unique structural features of the PKD1
      gene may be responsible for its mutability.

PMID- 8978604
TI  - Eomesodermin, a key early gene in Xenopus mesoderm differentiation.
AB  - Eomesodermin (Eomes) is a novel Xenopus T-domain gene. In normal development, it
      is expressed in mesodermal cells in a ventral-to-dorsal gradient of increasing
      concentration. It reaches its peak expression 1-2 hr before any other known
      panmesodermal gene. It is strongly inducible by normal vegetal cells and by
      mesoderm-inducing factors. Ectopic expression of Eomes in animal caps induces the
      transcription of nearly all mesodermal genes in a concentration-dependent way.
      Overexpression of Eomes dorsalizes ventral mesoderm, inducing gsc and changing
      cell fate to muscle and notochord. Blocking the function of Eomes causes
      gastrulation arrest and defective mesoderm-dependent gene activation. We propose
      that Eomes fulfills an essential function in initiating mesoderm differentiation
      and in determining mesodermal cell fate.

PMID- 8978605
TI  - Netrin-1 is required for commissural axon guidance in the developing vertebrate
      nervous system.
AB  - During nervous system development, spinal commissural axons project toward floor
      plate cells and trochlear motor axons extend away from these cells. Netrin-1, a
      diffusible protein made by floor plate cells, can attract spinal commissural
      axons and repel trochlear axons in vitro, but its role in vivo is unknown. Netrin
      1 deficient mice exhibit defects in spinal commissural axon projections that are
      consistent with netrin-1 guiding these axons. Defects in several forebrain
      commissures are also observed, suggesting additional guidance roles for netrin-1.
      Trochlear axon projections are largely normal, predicting the existence of
      additional cues for these axons, and evidence is provided for a distinct
      trochlear axon chemorepellent produced by floor plate cells. These results
      establish netrin-1 as a guidance cue that likely collaborates with other
      diffusible cues to guide axons in vivo.

PMID- 8978606
TI  - Long-term potentiation is reduced in mice that are doubly mutant in endothelial
      and neuronal nitric oxide synthase.
AB  - Nitric oxide (NO) has been implicated in hippocampal long-term potentiation
      (LTP), but LTP is normal in mice with a targeted mutation in the neuronal form of
      NO synthase (nNOS-). LTP was also normal in mice with a targeted mutation in
      endothelial NOS (eNOS-), but LTP in stratum radiatum of CA1 was significantly
      reduced in doubly mutant mice (nNOS-/eNOS-). By contrast, LTP in stratum oriens
      was normal in the doubly mutant mice. These results provide the first genetic
      evidence that NOS is involved in LTP in stratum radiatum and suggest that the
      neuronal and endothelial forms can compensate for each other in mice with a
      single mutation. They further suggest that there is also a NOS-independent
      component of LTP in stratum radiatum and that LTP in stratum oriens is largely
      NOS independent.

PMID- 8978607
TI  - Nitric oxide acts directly in the presynaptic neuron to produce long-term
      potentiation in cultured hippocampal neurons.
AB  - Nitric oxide (NO) has been proposed to act as a retrograde messenger during long
      term potentiation (LTP) in the CA1 region of hippocampus, but the inaccessibility
      of the presynaptic terminal has prevented a definitive test of this hypothesis.
      Because both sides of the synapse are accessible in cultured hippocampal neurons,
      we have used this preparation to investigate the role of NO. We examined LTP
      following intra- or extracellular application of an NO scavenger, an inhibitor of
      NO synthase, and a membrane-impermeant NO donor that releases NO only upon
      photolysis with UV light. Our results indicate that NO is produced in the
      postsynaptic neuron, travels through the extracellular space, and acts directly
      in the presynaptic neuron to produce long-term potentiation, supporting the
      hypothesis that NO acts as a retrograde messenger during LTP.

PMID- 8978608
TI  - A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid
      organs and specific anatomic compartments of the spleen.
AB  - We describe the phenotype of gene-targeted mice lacking the putative chemokine
      receptor BLR1. In normal mice, this receptor is expressed on mature B cells and a
      subpopulation of T helper cells. Blr1 mutant mice lack inguinal lymph nodes and
      possess no or only a few phenotypically abnormal Peyer's patches. The migration
      of lymphocytes into splenic follicles is severely impaired, resulting in
      morphologically altered primary lymphoid follicles. Furthermore, activated B
      cells fail to migrate from the T cell-rich zone into B cell follicles of the
      spleen, and despite high numbers of germinal center founder cells, no functional
      germinal centers develop in this organ. Our results identify the putative
      chemokine receptor BLR1 as the first G protein-coupled receptor involved in B
      cell migration and localization of these cells within specific anatomic
      compartments.

PMID- 8978609
TI  - The Drosophila beaten path gene encodes a novel secreted protein that regulates
      defasciculation at motor axon choice points.
AB  - In the Drosophila embryo, at specific choice points along the major motor nerves,
      subsets of motor axons defasciculate and then steer into their muscle target
      regions. Here we describe the analysis of beaten path (beat), a gene required for
      the selective defasciculation of motor axons at these choice points. In beat
      mutant embryos, motor axons fail to defasciculate and bypass their targets. This
      phenotype is suppressed by mutations in FasII and conn, two genes encoding cell
      adhesion molecules expressed on motor axons, suggesting that beat provides an
      antiadhesive function. beat encodes a novel secreted protein that is expressed by
      motoneurons during outgrowth. Rescue and ectopic expression experiments support
      the model that Beat protein is secreted by motor axons where it functions to
      regulate their selective defasciculation at specific choice points.

PMID- 8978610
TI  - A Drosophila neurexin is required for septate junction and blood-nerve barrier
      formation and function.
AB  - Septate and tight junctions are thought to seal neighboring cells together and to
      function as barriers between epithelial cells. We have characterized a novel
      member of the neurexin family, Neurexin IV (NRX), which is localized to septate
      junctions (SJs) of epithelial and glial cells. NRX is a transmembrane protein
      with a cytoplasmic domain homologous to glycophorin C, a protein required for
      anchoring protein 4.1 in the red blood cell. Absence of NRX results in
      mislocalization of Coracle, a Drosophila protein 4.1 homolog, at SJs and causes
      dorsal closure defects similar to those observed in coracle mutants. nrx mutant
      embryos are paralyzed, and electrophysiological studies indicate that the lack of
      NRX in glial-glial SJs causes a breakdown of the blood-brain barrier. Electron
      microscopy demonstrates that nrx mutants lack the ladder-like intercellular septa
      characteristic of pleated SJs (pSJs). These studies identify NRX as the first
      transmembrane protein of SJ and demonstrate a requirement for NRX in the
      formation of septate-junction septa and intercellular barriers.

PMID- 8978611
TI  - Fibrillar collagen inhibits arterial smooth muscle proliferation through
      regulation of Cdk2 inhibitors.
AB  - Arterial smooth muscle cells (SMCs) are arrested in the G1 phase of the cell
      cycle on polymerized type I collagen fibrils, while monomer collagen supports SMC
      proliferation. Cyclin E-associated kinase and cyclin-dependent kinase 2 (cdk2)
      phosphorylation are inhibited on polymerized collagen, and levels of the cdk2
      inhibitors p27Kip1 and p21Cip1/Waf1 are increased compared with SMCs on monomer
      collagen. p27Kip1 associates with the cyclin E-cdk2-p21Cip1/Waf1 complex in SMCs
      on polymerized collagen. Monovalent blocking antibodies to alpha2 integrins,
      integrins that mediate adhesion to both forms of collagen, mimic these effects on
      monomer collagen. Furthermore, polymerized collagen rapidly suppresses p70 S6
      kinase, a possible regulator of p27Kip1. Thus, fibrillar collagen specifically
      regulates early integrin signaling that may lead to up-regulation of cdk2
      inhibitors and inhibition of SMC proliferation.

PMID- 8978612
TI  - Control of male sexual behavior and sexual orientation in Drosophila by the
      fruitless gene.
AB  - Sexual orientation and courtship behavior in Drosophila are regulated by
      fruitless (fru), the first gene in a branch of the sex-determination hierarchy
      functioning specifically in the central nervous system (CNS). The phenotypes of
      new fru mutants encompass nearly all aspects of male sexual behavior. Alternative
      splicing of fru transcripts produces sex-specific proteins belonging to the BTB
      ZF family of transcriptional regulators. The sex-specific fru products are
      produced in only about 500 of the 10(5) neurons that comprise the CNS. The
      properties of neurons expressing these fru products suggest that fru specifies
      the fates or activities of neurons that carry out higher order control functions
      to elicit and coordinate the activities comprising male courtship behavior.

PMID- 8978613
TI  - branchless encodes a Drosophila FGF homolog that controls tracheal cell migration
      and the pattern of branching.
AB  - The molecular basis for patterning of complex organ structures like the lung and
      insect tracheal system is unknown. Here, we describe the Drosophila gene
      branchless (bnl) and demonstrate that it is a key determinant of the tracheal
      branching pattern. bnl is required for tracheal branching and is expressed
      dynamically in clusters of cells surrounding the developing tracheal system at
      each position where a new branch will form and grow out. Localized misexpression
      of bnl can direct branch formation and outgrowth to new positions. Generalized
      misexpression activates later programs of tracheal gene expression and branching,
      resulting in massive networks of branches. bnl encodes a homolog of mammalian
      fibroblast growth factors (FGFs) and appears to function as a ligand for the
      breathless receptor tyrosine kinase, an FGF receptor homolog expressed on
      developing tracheal cells. The results suggest that this FGF pathway specifies
      the tracheal branching pattern by guiding tracheal cell migration during primary
      branch formation and then activating later programs of finer branching at the
      ends of growing primary branches.

PMID- 8978614
TI  - Chromatid segregation at anaphase requires the barren product, a novel chromosome
      associated protein that interacts with Topoisomerase II.
AB  - We have isolated a Drosophila gene, barren (barr), required for sister-chromatid
      segregation in mitosis. barr encodes a novel protein that is present in
      proliferating cells and has homologs in yeast and human. Mitotic defects in barr
      embryos become apparent during cycle 16, resulting in a loss of PNS and CNS
      neurons. Centromeres move apart at the metaphase-anaphase transition and Cyclin B
      is degraded, but sister chromatids remain connected, resulting in chromatin
      bridging. This phenotype is similar to that described in TOP2 mutants in yeast.
      Barren protein localizes to chromatin throughout mitosis. Colocalization and
      biochemical experiments indicate that Barren associates with Topoisomerase II
      throughout mitosis and alters the activity of Topoisomerase II. We propose that
      this association is required for proper chromosomal segregation by facilitating
      the decatenation of chromatids at anaphase.

PMID- 8978615
TI  - Induction of large DNA palindrome formation in yeast: implications for gene
      amplification and genome stability in eukaryotes.
AB  - Many amplified genes, including some oncogenes, are organized as large inverted
      repeats. How such giant palindromes are generated remains largely unknown. Recent
      studies of a palindrome in the ciliate Tetrahymena suggest a novel mechanism that
      requires chromosome breakage next to short inverted repeats. The prevalence of
      short inverted repeats in eukaryotic genomes raises the interesting possibility
      that this process may occur widely as a response to chromosome damage. Here we
      demonstrate that in Saccharomyces cerevisiae, large DNA palindromes are formed
      efficiently, probably by intramolecular recombination, when a double-strand break
      is introduced next to short inverted repeats. These results suggest a general
      mechanism for large palindromic DNA formation and reveal an important new source
      of genome instability resulting from chromosome breakage at selective sites.

PMID- 8978616
TI  - Transcription activation at class II CAP-dependent promoters: two interactions
      between CAP and RNA polymerase.
AB  - At Class II catabolite activator protein (CAP)-dependent promoters, CAP activates
      transcription from a DNA site overlapping the DNA site for RNA polymerase. We
      show that transcription activation at Class II CAP-dependent promoters requires
      not only the previously characterized interaction between an activating region of
      CAP and the RNA polymerase alpha subunit C-terminal domain, but also an
      interaction between a second, promoter-class-specific activating region of CAP
      and the RNA polymerase alpha subunit N-terminal domain. We further show that the
      two interactions affect different steps in transcription initiation.
      Transcription activation at Class II CAP-dependent promoters provides a paradigm
      for understanding how an activator can make multiple interactions with the
      transcription machinery, each interaction being responsible for a specific
      mechanistic consequence.

PMID- 8978618
TI  - Neurophysiology of focal malformations of cortical development.

PMID- 8978617
TI  - A tyrosyl-tRNA synthetase recognizes a conserved tRNA-like structural motif in
      the group I intron catalytic core.
AB  - The Neurospora crassa mitochondrial (mt) tyrosyl-tRNA synthetase (CYT-18 protein)
      functions in splicing group I introns, in addition to aminoacylating tRNA(Tyr).
      Here, we compared the CYT-18 binding sites in the N. crassa mt LSU and ND1
      introns with that in N. crassa mt tRNA(Tyr) by constructing three-dimensional
      models based on chemical modification and RNA footprinting data. Remarkably,
      superimposition of the CYT-18 binding sites in the model structures revealed an
      extended three-dimensional overlap between the tRNA and the group I intron
      catalytic core. Our results provide insight into how an RNA-splicing factor can
      evolve from a cellular RNA-binding protein. Further, the structural similarities
      between group I introns and tRNAs are consistent with an evolutionary
      relationship and suggest a general mechanism for the evolution of complex
      catalytic RNAs.

PMID- 8978619
TI  - Pathogenesis and pathology of focal malformations of cortical development and
      epilepsy.
AB  - This article reviews the pathogenesis and pathology of the most common focal
      malformations of cortical development in association with epilepsy. The
      classification of these disorders is reviewed in the context of new developments
      in the areas of diagnosis and genetics. The major pathological substrates and the
      possible mechanisms of these malformations are discussed. The possible mechanisms
      of epileptogenesis in the context of focal malformations are complex and poorly
      understood at present. Advances in this area promise to enhance our understanding
      of the basic mechanisms of epilepsy.

PMID- 8978620
TI  - Neuroimaging of focal malformations of cortical development.
AB  - Neuroimaging is playing an increasingly important role in the evaluation of
      patients with malformations of cerebral cortical development. In this review, the
      authors address optimal neuroimaging of cortical malformations using x-ray
      computed tomography, single-photon-emission computed tomography, positron
      emission tomography, magnetic resonance imaging, and magnetic resonance
      spectroscopy. Initially, the authors discuss the strengths and weaknesses of the
      various imaging techniques. This is followed by a discussion of the clinical and
      neuroimaging characteristics of several different imaging manifestations of focal
      malformations of cortical development, including polymicrogyria, focal
      subcortical heterotopia, schizencephaly, focally thickened gyri, focally
      irregular gyri, hemimegalencephaly, and transmural dysplasia. The authors intend
      that, after reading this review, the reader will have a better understanding of
      the optimal neuroimaging techniques for evaluating these malformations and their
      many neuroimaging appearances.

PMID- 8978621
TI  - EEG features of focal malformations of cortical development.
AB  - Recent advances in neuroimaging have allowed the detection and characterization
      of focal malformations of cortical developmental in a significant proportion of
      patients with epilepsy, many of whom were previously labelled as cryptogenic,
      allowing a better description of the associated electroencephalogram (EEG)
      features. Alpha activity is usually preserved, although superficial gyral
      abnormalities are often associated with overlying localized polymorphic delta
      activity, and occasionally abnormal fast activity. Most affected patients with
      epilepsy show interictal spikes. These are often broadly concordant with the
      structural abnormality but may show a wider anatomic distribution and be
      multifocal, or occasionally appear only in anatomically distant sites. In many
      patients the spikes are frequent and sometimes they occur continuously or in long
      trains. EEG findings are often stable over time, but some patients only show the
      development of slow wave changes or interictal spikes when followed serially for
      several years. A small proportion of patients with focal malformations of
      cortical development have EEG features mimicking idiopathic generalized epilepsy,
      and occasionally patients exhibit continuous generalized spike and slow wave
      activity in sleep. Electrocorticography studies confirm the often widespread
      nature of interictal spiking, but may also show highly epileptogenic patterns
      recorded directly from dysplastic cortex. The intrinsic epileptogenicity of areas
      of cortical developmental abnormalities has also been demonstrated by chronic
      intracranial studies and in vitro recordings of slices obtained from resected
      human dysplastic cortex. In this regard such developmental abnormalities are
      fundamentally different from acquired lesions such as tumors/vascular anomalies
      that usually exert their effects through changes in adjacent cortex.

PMID- 8978622
TI  - Value of full-field visual evoked potentials for retrochiasmal lesions.
AB  - Some abnormalities in the P100 on monocular stimulation have been said to
      indicate retrochiasmal abnormalities. This study was undertaken to evaluate the
      reliability of visual evoked potentials (VEPs) for this purpose. We
      retrospectively reviewed VEPs that could be interpreted as indicative of a
      retrochiasmal lesion, based on an amplitude asymmetry of >50% between the P100
      recorded on the left and right occipital regions. The abnormality had to be
      present on both left and right monocular stimulation (uncrossed pattern). Studies
      were conducted in accordance with the guidelines of the American
      Electroencephalographic Society. Findings on magnetic resonance (MR) imaging were
      analyzed. For comparison, we also studied a control group of 30 patients with
      normal VEPs. During a 16-month period, we identified 15 patients who fulfilled
      the aforementioned criteria and who had undergone an MR scan of the brain. Eight
      scans were normal and seven were abnormal. Of the seven abnormal scans, five
      revealed multiple periventricular white matter lesions in both hemispheres
      suggestive of multiple sclerosis: one a single punctate white matter lesion in
      the left frontal corona radiata, and one multiple white matter lesions in the
      basal ganglia, brainstem, and cerebellum but not in the hemispheres. In the
      control group with normal VEPs, nine had at least one hemispheric lesion on MR
      scans. This yielded a positive predictive value of 33%. The negative predictive
      value was 70%, sensitivity 36%, and specificity 68%. Because of a high rate of
      false positives, full-field VEPs were not reliable in predicting retrochiasmal
      lesions.

PMID- 8978623
TI  - Alpha frequency, reaction time, and the speed of processing information.
AB  - Several experiments indicate that alpha frequency is significantly correlated
      with the speed of information processing, as measured by reaction times. These
      data imply that alpha frequency is a timing mechanism for cognitive processes.
      However, this interpretation contradicts the well-accepted view that there is no
      single alpha rhythm, but instead an entire population of different alpha
      oscillations. We present arguments and report data in the attempt to demonstrate
      that this paradox can be resolved if different states of alpha oscillations are
      distinguished. The results of the present study show that during a state of
      desynchronization, task-related shifts in alpha frequency are not "real" because
      they are not related to reaction times. Instead, they most likely reflect power
      changes in different frequency bands.

PMID- 8978624
TI  - Periodic lateralized epileptiform discharges--a critical review.
AB  - It is the purpose of this review to critically consider and organize the
      literature dealing with the ephemeral electroencephalographic (EEG) pattern
      periodic lateralized epileptiform discharges (PLEDs). Although the retrospective
      nature of these studies limits their ability to discuss accurately the clinical
      and pathophysiological aspects of this EEG entity, the available data strongly
      emphasize stroke as the dominant etiology and its high association with seizures.
      Recent evidence, particularly from functional neuroimaging studies, strongly
      suggests that PLEDs might reflect a key pattern for focal hyperexcitability in
      the penumbra zone of ischemic stroke. The authors prefer to consider PLEDs as an
      EEG signature of a dynamic pathophysiological state in which unstable
      neurobiological processes create an ictal-interictal continuum, with the nature
      of the underlying neuronal injury, the patient's preexisting propensity to have
      seizures, and the co-existence of any acute metabolic derangements all
      contributing to whether seizures occur or not. This review underlines the need
      for further sophisticated prospective controlled studies implementing early
      continuous EEG monitoring in order to contribute to an understanding of the
      incidence, dynamics, and relevance of this pattern.

PMID- 8978626
TI  - Characterization and prediction of gradient acoustic noise in MR imagers.
AB  - Gradient acoustic noise has been measured and characterized for an epoxy-potted,
      shielded gradient assembly in a 1.5 T MRI system. Noise levels vary by 10 dB or
      more as a function of longitudinal position in the scanner and reflect the
      pattern of forces applied to the gradient assembly. The noise level increases
      slightly (1-3 dB) with a patient in the scanner. The spectrum of the noise is
      similar (but not identical) to the spectrum of the input signal. A gradient-pulse
      to-acoustic-noise transfer function was obtained by using a white noise voltage
      input to the gradient system. The transfer function enabled us to accurately
      predict acoustic noise output for a pulse sequence consisting of a series of
      trapezoidal pulses on a single axis and for a clinical fast spin echo sequence
      with gradients present on all three axes.

PMID- 8978625
TI  - Reversible, reproducible reduction of brain water apparent diffusion coefficient
      by cortical electroshocks.
AB  - Rat brains were imaged after cortical electroshock pulse trains (1 ms pulses at
      100 Hz) of varying durations (0.1-10 s), with diffusion-weighted echo planar
      imaging sequences at 2.0 T. The apparent water diffusion coefficient (ADC)
      decreased after either single or repeat electroshock trains. ADC reductions were
      observed within 6 s after the first shock. The size of the affected area of the
      brain increased in subsequent images during the 1st min after a 10-pulse (0.1 s)
      train, and also increased with the duration of electroshock trains. ADC reduction
      was reproducible in extent and time course after single 10-shock trains and was
      reversible. In the affected pixels the mean ADC reduction was 4% for a single
      shock train (0.1 s), and 7-8% for trains repeated once a minute, independent of
      electroshock train duration. The results indicate that neuronal activity
      associated with electrostimulation may be monitored with water diffusion
      measurements, and they may be useful for measuring the severity of seizure
      activity in patients with medically intractable epilepsy.

PMID- 8978627
TI  - Multinuclear solid-state NMR spectroscopy of envelopes from virgin and explanted
      silicone breast prostheses: an exploratory study.
AB  - The structure and dynamics of silicone envelopes from virgin and explanted breast
      prostheses have been studied by 1H, 13C, and 29Si high-resolution solid-state NMR
      spectroscopy. The results indicate that this combination of techniques can be
      used to unambiguously identify the presence of methyltrifluoropropylsiloxane
      units and diphenylsiloxane units at concentrations of about 2.0% and 3.5%,
      respectively, in some of the envelopes. The presence of about 10% silica also was
      detected and a trace of lipids was found in the explanted silicone envelopes. We
      have also measured the proton T2 and T1 relaxation times of the envelopes to
      characterize the dynamics of the silicone in the envelopes.

PMID- 8978628
TI  - Temporal lobe epilepsy: correlation of proton magnetic resonance spectroscopy and
      18F-fluorodeoxyglucose positron emission tomography.
AB  - Proton magnetic resonance spectroscopy (MRS) has demonstrated reduction of N
      acetylaspartate (NAA) in the epileptogenic temporal lobe. However, the
      correlation of NAA reduction with cerebral metabolic abnormalities is unknown in
      temporal lobe epilepsy (TLE). Proton MRS and 18F-fluorodeoxyglucose positron
      emission tomography (FDG/PET) were used to study 12 unilateral TLE patients with
      medically intractable seizures and 26 age-matched healthy volunteers. The
      epileptogenic temporal lobe of each patient was determined by both
      electroencephalography and FDG/PET. The NAA/choline-plus-creatine (NAA/(Cho+Cr))
      ratio correlated significantly with the interictal glucose metabolism (r = 0.54,
      P < 0.01) in 12 TLE patients. The mean NAA/(Cho+Cr) ratio in the epileptogenic
      temporal lobe was significantly less than that in the contralateral side (P <
      0.01), and less than that in normal control temporal lobes (P < 0.0001). These
      results suggest that quantitative MRS abnormalities reflect underlying metabolic
      pathology in TLE.

PMID- 8978629
TI  - Histological and 1H magnetic resonance spectroscopic imaging analysis of
      quinolinic acid-induced damage to the rat striatum.
AB  - NAA has been described as a neuron-specific compound. NAA levels as determined by
      magnetic resonance spectroscopic imaging (MRSI) have been used to determine
      degree of neuronal loss in several neurological diseases, but there has been
      limited work to document the accuracy and reliability of this technique. This
      study addresses this question quantitatively with histological analysis of cell
      viability and tissue shrinkage in quinolinic acid (QA)-induced damage of the rat
      striatum compared with 1H MRSI measurement of N-acetyl aspartate (NAA) as a
      noninvasive measure of neuronal loss. Both 1H MRSI and histology detect damage to
      the lesioned striatum; however, there are differences in the degree of damage as
      assessed by the two methods. Although partial-volume effects and tissue shrinkage
      may decrease the sensitivity of MR to such damage, the sparing of axons by QA may
      be another important factor in the differences in assessment. These results
      indicate that further studies of NAA metabolism and its distribution within
      neurons are warranted.

PMID- 8978630
TI  - In vivo measurement of T2 distributions and water contents in normal human brain.
AB  - Using a 32-echo imaging pulse sequence, T2 relaxation decay curves were acquired
      from five white- and six gray-matter brain structures outlined in 12 normal
      volunteers. The water contents of white and gray matter were 0.71 (0.01) and 0.83
      (0.03) g/ml, respectively. All white-matter structures had significantly higher
      myelin water percentages (signal percentage with T2 between 10 and 50 ms) than
      all gray-matter structures. The range in geometric mean T2 of the main peak for
      both white and gray matter was from 70 to 86 ms. T2 distributions from the
      posterior internal capsules and splenium of the corpus callosum were
      significantly wider (width is related to water environment inhomogeneity) than
      those from any other white- or gray-matter structures. Thus, quantitative
      measurement and analysis of T2 relaxation reveals differences in brain tissue
      water environments not discernible on conventional MR images. These differences
      may make short T2 components reliable markers for normal myelin.

PMID- 8978631
TI  - Diffusion of solutes in agarose and alginate gels: 1H and 23Na PFGSE and 23Na TQF
      NMR studies.
AB  - Cells immobilized in gels experience potential metabolic restrictions in the form
      of reduced diffusion rates of metabolites and ions and their possible selective
      adsorption on the gel matrix. Diffusion and relaxation characteristics of common
      solutes in agarose and barium alginate gels were investigated at 37 degrees C by
      using 1H PFGSE and 23Na TQF NMR spectroscopy. Glucose, glycine, alanine, lactate,
      sodium ions, and HDO were studied. There were no selective interactions between
      any of the metabolites and the gel materials but the diffusion coefficients were
      uniformly reduced. The effects of metabolite diffusion and utilization, in gel
      beads and threads containing cells, were simulated by using a reaction diffusion
      model incorporating the measured diffusion coefficients. Metabolism is expected
      to be very significantly limited by diffusion of solutes to and from the cells
      that are centrally located within gel threads or spheres of radius approximately
      2.0 mm, which is a commonly used size.

PMID- 8978632
TI  - T1rho of protein solutions at very low fields: dependence on molecular weight,
      concentration, and structure.
AB  - The effect of molecular weight, concentration, and structure on 1/T1rho, the
      rotating frame relaxation rate, was investigated for several proteins using the
      on-resonance spin-lock technique, for locking fields B1 < 200 microT. The
      measured values of 1/T1rho were fitted to a simple theoretical model to obtain
      the dispersion curves 1/T1rho(omega1) and the relaxation rate at zero B1 field,
      1/T1rho(0). 1/T1rho was highly sensitive to the molecular weight, concentration,
      and structure of the protein. The amount of intra- and intermolecular hydrogen
      and disulfide bonds especially contributed to 1/T1rho. In all samples, 1/T1rho(0)
      was equal to 1/T2 measured at the main magnetic field Bo = 0.1 T, but at higher
      locking fields the dispersion curves monotonically decreased. The results of this
      work indicate that a model considering the effective correlation time of
      molecular motions as the main determinant for T1rho relaxation in protein
      solutions is not valid at very low B1 fields. The underlying mechanism for the
      relaxation rate 1/T1rho at B1 fields below 200 microT is discussed.

PMID- 8978633
TI  - Estimation of water extraction fractions in rat brain using magnetic resonance
      measurement of perfusion with arterial spin labeling.
AB  - The model used for calculating perfusion by MRI techniques that use endogenous
      water as a tracer assumes that arterial water is a freely diffusible tracer.
      Evidence shows that this assumption is not valid in the brain at high blood flow
      rates, at which movement of water into and out of the microvasculature becomes
      limited by diffusion across the blood-brain barrier. In this work, the arterial
      spin-labeling technique is used to show that fraction of arterial water that is
      dependent on blood flow rate remains in the vasculature and does not exchange
      with brain tissue water. By using perfusion measurements without and with
      magnetization transfer (MT) effects, one can distinguish arterial label that
      exchanges into tissue because blood has much smaller MT than brain tissue. Using
      this technique, the extraction fraction for water is measured in the rat brain at
      various cerebral blood flow rates. At high flow rates (approximately 5 ml/g/min),
      the extraction fraction for water is found to be about 45% in rat brain.
      Disruption of the blood-brain barrier with D-mannitol caused an increase in the
      extraction fraction for water. It was possible to form an image related to the
      extraction fraction for water. The ability to estimate the amount of vascular
      water exchanging with tissue water by MRI may represent a noninvasive approach to
      detect the integrity of the blood-brain barrier.

PMID- 8978634
TI  - Measurement of strain exerted on blood vessel walls by double-quantum-filtered 2H
      NMR.
AB  - In this study 2H double quantum-filtered (DQF) NMR spectroscopy of water
      molecules inside the blood vessel wall was used to monitor structural changes
      after the application of strain. This method was applied to a variety of bovine
      large blood vessels, including aorta, coronary artery, carotid artery, and vena
      cava. Inducing strain in coronary arteries by inflating them by air or water
      revealed dramatic changes in the 2H DQF spectral lineshapes. Uniaxial extensions
      of longitudinal and circumferential strips led to distinct spectral responses for
      the different blood vessels. While the spectral lineshapes for the coronary and
      the carotid arteries were very sensitive to longitudinal strain, they were not
      affected by circumferential stretching. For the aorta there were no changes in
      the lineshape upon strain. For the vena cava a large effect of strain was found
      that was independent of the choice of elongation axis. The effect of elongation
      on the spectra was assigned to the outer layer, the adventitia, whereas spectral
      lineshapes that originated from inner layers, media and intima, were almost
      insensitive to strain. Angular dependence experiments proved the presence of
      macroscopic order in the strained state superimposed on a broad distribution of
      the local directors. Our results demonstrate the sensitivity of 2H DQF NMR as a
      probe for dynamic processes occurring on the microscopic scale in a molecular
      network.

PMID- 8978635
TI  - An FEM approach for the characterization of the RF field homogeneity at high
      field.
AB  - High field magnetic resonance offers new opportunities because of its high SNR
      and better spectral resolution for MRI and MRS. However, new problems also emerge
      at high field. As the field strength increases, the wavelength in the tissue
      becomes shorter and comparable with the body dimensions. This perturbs the field
      and also causes standing waves within the patient as a result of the impedance
      mismatching at the tissue interfaces. Due to the complexity of the boundary
      conditions and the solution of Maxwell's equations, an exact analytical
      calculation for a loaded RF resonator has not been possible. In this paper, we
      present a birdcage coil simulation study based on a 3D finite element method
      (FEM) model for the characterization of the field within the tissue. First, the
      accuracy of the FEM solutions is validated by the 2D analytical solutions at 64
      and 223 MHz. In these solutions, the frequency dependence of the conductivity and
      permittivity is also taken into account. Then, a more realistic 3D model is
      studied. The results are compared with the experimental measurements. It is shown
      that the 3D model makes it possible to explore the effects of the end rings in
      the presence of a tissue sample inside the coil.

PMID- 8978636
TI  - Unsupervised, automated segmentation of the normal brain using a multispectral
      relaxometric magnetic resonance approach.
AB  - The purpose of this study was the development and testing of a method for
      unsupervised, automated brain segmentation. Two spin-echo sequences were used to
      obtain relaxation rates and proton-density maps from 1.5 T MR studies, with two
      axial data sets including the entire brain. Fifty normal subjects (age range, 16
      to 76 years) were studied. A Three-dimensional (3D) spectrum of the tissue voxels
      was used for automatic segmentation of gray matter (GM), white matter (WM), and
      cerebrospinal fluid (CSF) and for calculation of their volumes. Accuracy and
      reproducibility were tested with a three-compartment phantom simulating GM, WM,
      and CSF. In the normal subjects, a significant decrease of GM fractional volume
      and increased CSF volume with age were observed (P < 0.0001), with no significant
      changes in WM. This multispectral segmentation method permits reproducible,
      operator-independent volumetric measurements.

PMID- 8978637
TI  - A dual approach for minimizing false lesion classifications on magnetic resonance
      images.
AB  - Segmentation methods based on dual-echo MR images are generally prone to
      significant false lesion classifications. We have minimized these false
      classifications by (1) improving the lesion-to-tissue contrast on MR images by
      developing a fast spin-echo sequence that incorporates both cerebrospinal fluid
      signal attenuation and magnetization transfer contrast and (2) including
      information from MR flow images. Studies on patients with multiple sclerosis
      indicate that this dual approach to tissue segmentation reduces the volume of
      false lesion classifications by an average of 87%.

PMID- 8978638
TI  - An analytical model of restricted diffusion in bovine optic nerve.
AB  - An analytical model of restricted diffusion in bovine optic nerve is presented.
      The nerve tissue model is composed of two different objects: prolate ellipsoids
      (axons) and spheres (glial cells) surrounded by partially permeable membranes.
      The free diffusion coefficients of intracellular and extracellular water may
      differ. Analytical formulas for signal loss due to diffusion in the pulsed
      gradient spin echo (PGSE) experiment for this tissue model are derived. The model
      is fitted to experimental data for bovine optic nerve. The obtained model
      parameters are shown to be reasonable. The model describes all of the
      characteristics of the PGSE data: anisotropy, upward curvature of decay curves,
      and diffusion time dependence. The validity and sensitivity of the model are also
      discussed.

PMID- 8978639
TI  - Intravascular magnetic resonance imaging using a loopless catheter antenna.
AB  - Recently, intravascular catheter probes have been developed to increase signal-to
      noise ratio (SNR) for MR imaging of blood vessels. Miniaturization of these
      catheter probes without degrading their performances is very critical in imaging
      small vessels such as coronary arteries. Catheter coils have a loop incorporated
      in their structure and have limitations in physical dimensions and
      electromagnetic properties. The use of a loopless intravascular catheter antenna
      is proposed to overcome these problems. The catheter antenna is essentially a
      dipole, which makes a very thin diameter possible, and its electronic circuitry
      can be placed outside the blood vessels without performance degradation. The
      theoretical foundation for the design and operation of the catheter antenna is
      presented. Several catheter antennae, as small as 1.5 French, were constructed
      and tested on phantoms and rabbits with great success. The catheter antenna has a
      simple structure and is easy to design, implement, and operate.

PMID- 8978640
TI  - Cerebrospinal fluid-suppressed high-resolution diffusion imaging of human brain.
AB  - A cerebrospinal fluid (CSF)-suppressed flow-attenuated inversion recovery (FLAIR)
      double-shot diffusion echo-planar imaging (EPI) sequence was developed and used,
      along with a non-CSF-suppressed version of the sequence, to determine the extent
      of the contribution of CSF partial-volume averaging to the apparent diffusion
      coefficients (ADCs) of normal human brain in vivo. Regional analysis indicates
      that cortical gray matter and parenchymal tissues bordering the ventricles are
      most affected by CSF contamination, leading to elevated ADC values. Only slight
      differences in gray- and white-matter average ADCs were detected after CSF
      suppression. The human brain average ADCs calculated from high-resolution CSF
      suppressed diffusion-weighted images in these studies are similar to those
      reported in animals. FLAIR diffusion sequences remove CSF as a source of error in
      ADC determination and ischemic lesion discrimination in diffusion-weighted images
      (DWI) and ADC maps.

PMID- 8978642
TI  - Decoupled automated rotational and translational registration for functional MRI
      time series data: the DART registration algorithm.
AB  - A rapid, in-plane image registration algorithm that accurately estimates and
      corrects for rotational and translational motion is described. This automated,
      one-pass method achieves its computational efficiency by decoupling the
      estimation of rotation and translation, allowing the application of rapid cross
      correlation and cross-spectrum techniques for the determination of displacement
      parameters. k-space regridding and modulation techniques are used for image
      correction as alternatives to linear interpolation. The performance of this
      method was analyzed with simulations and echo-planar image data from both
      phantoms and human subjects. The processing time for image registration on a
      Hewlett-Packard 735/125 is 7.5 s for a 128 x 128 pixel image and 1.7 s for a 64 x
      64 pixel image. Imaging phantom data demonstrate the accuracy of the method (mean
      rotational error, -0.09 degrees; standard deviation = 0.17 degrees; range, -0.44
      degrees to +0.31 degrees; mean translational error = -0.035 pixels; standard
      deviation = 0.054 pixels; range, -0.16 to +0.06 pixels). Registered human
      functional imaging data demonstrate a significant reduction in motion artifacts
      such as linear trends in pixel time series and activation artifacts due to
      stimulus-correlated motion. The advantages of this technique are its noniterative
      one-pass nature, the reduction in image degradation as compared to previous
      methods, and the speed of computation.

PMID- 8978641
TI  - Techniques for high-speed cardiac magnetic resonance imaging in rats and rabbits.
AB  - Progress in research on hypertension, heart failure, aging, post-infarct
      remodeling, and the molecular basis of cardiovascular diseases in general has
      been greatly facilitated in recent years by the development of specialized small
      mammal models by selective breeding and/or genetic alteration. Routine
      noninvasive evaluation of cardiac function and perfusion in these animals models,
      however, is difficult using existing methods. In principle, MRI can be used for
      this purpose, but in practice this is difficult because of problems related to RF
      coils, cardiac gating, and imaging pulse sequences. In this article, solutions to
      these problems are described that have allowed us to use MRI to routinely image
      the hearts of rats and rabbits. Specifically described are four RF coils, cardiac
      gating schemes, and an imaging pulse sequence specially designed for cardiac
      imaging in these animals on a 4.7 T Omega chemical-shift imaging (CSI)
      spectrometer. These techniques can be used to obtain, within 2 min, eight double
      oblique short-axis images of the rat at different cardiac phases with 200 x 400
      microm in-plane resolution and a slice thickness of 2 mm. Moreover, myocardial
      tissue tagging can be performed with tag thicknesses and separations comparable
      to those used routinely in humans. The technical information is presented in
      sufficient detail to allow researchers at other sites to reproduce the results.
      This information should facilitate the use of MRI for the noninvasive examination
      of cardiac function and perfusion, which can be combined with other established
      techniques for the study of cardiovascular disease in specialized animal models.

PMID- 8978644
TI  - Prospective adaptive navigator correction for breath-hold MR coronary
      angiography.
AB  - Current MR coronary angiography (MRCA) methods use breath-holding to minimize
      respiratory motion. A major limitation to this technique is misregistration
      between imaging slices due to breath-hold variability. Prospective adaptive
      correction of image location using real-time navigator measurement of diaphragm
      position is a potential method for improving slice registration in breath-hold
      MRCA. Ten subjects underwent MRCA using an ECG-gated, fat-suppressed, segmented k
      space, gradient-echo sequence. Transverse and coronal images were acquired using
      standard breath-holding with and without prospective navigator correction. Breath
      hold MRCA with prospective navigator correction resulted in a 47% reduction in
      craniocaudal slice registration error compared to standard breath-holding (0.9 +/
      0.2 mm versus 1.7 +/- 0.4 mm, P = 0.04). Prospective adaptive navigator
      correction of image location significantly improves slice registration for breath
      hold MRCA and is a promising motion correction technique for cardiac MR.

PMID- 8978643
TI  - Normal myocardial perfusion assessed with multishot echo-planar imaging.
AB  - A new magnetic resonance imaging strategy is presented for accessing myocardial
      perfusion. Most previous work has relied on using T1-weighted fast gradient-echo
      imaging to monitor dynamically the signal changes during the passage of a
      contrast media bolus. However, the gradient-echo approach is limited by an
      inability to image the entire heart with adequate temporal resolution. This paper
      focuses on a electrocardiogram-gated multishot echo-planar imaging sequence,
      using the simple strategy of using the intrinsic T1 weighting produced by a
      repetition time equal to the heart period. To quantitate the sequence's
      performance with respect to normal myocardial perfusion, seven volunteers were
      imaged, each with three different doses of the contrast medium gadolinium
      diethylenetriamine pentaacetic acid (Gd-DTPA). The first-pass dynamics of the
      contrast were quantified in 13 regions per heart for each examination. In all
      volunteers, the complete heart could be covered, with five to seven slices, every
      two heartbeats. Enhancement was homogeneous throughout the left ventricular
      myocardium, with an enhancement of approximately 50% for the optimum contrast
      dose of 0.05 mmol/kg Gd-DTPA.

PMID- 8978645
TI  - Magnetization and diffusion effects in NMR imaging of hyperpolarized substances.
AB  - The special magnetization characteristics of hyperpolarized noble gases have led
      to an interest in using these agents for new MRI applications. In this note, the
      magnetization effects and NMR signal dependence of two noble gases, 3He and
      l29Xe, are modeled across a range of gradient-echo imaging parameters. Pulse
      sequence analysis shows a wide variation in optimum flip angles between imaging
      of gas (e.g., 3He or 129Xe) in air spaces (e.g., trachea and lung) and in blood
      vessels. To optimize imaging of the air spaces, it is also necessary to reduce
      the otherwise substantial signal losses from diffusion effects by increasing
      voxel size. The possibility of using hyperpolarized 129Xe for functional MRI
      (fMRI) is discussed in view of the results from the blood flow analysis. The
      short-lived nature of the hyperpolarization opens up new possibilities, as well
      as new technical challenges, in its potential application as a blood-flow tracer.

PMID- 8978646
TI  - Effects of aging on titanium implants inserted into the tibiae of female rats
      using light microscopy, SEM, and image processing.
AB  - We examined the influence of aging on the implant-bone interface of titanium
      implants inserted transcortically and extending into the medullary canal of rat
      tibiae, and quantitatively assessed the differences in bone reaction using an
      image processing system. Three groups of 15 female rats, aged 6 weeks (young
      group), 22 weeks (adult group), and 80 weeks (old group) were used in this
      experiment. The animals were sacrificed 28 days after implant placement.
      Toluidine blue stained undecalcified sections were prepared for histological
      observation and image analysis, and the implant socket was observed by SEM. There
      was no difference in the degree of maturation of newly formed bone between the
      young and adult groups. Titanium implants inserted in the young and adult groups
      were surrounded with a bone layer. In the old group, however, there was little
      mature bone tissue around the implants. Quantitative evaluation indicated that
      the young group showed the highest, the adult group showed a slightly lower, and
      the old group showed the lowest percent bone contact, thickness of bone contact,
      and area of bone surrounding the implant.

PMID- 8978647
TI  - Fretting corrosion resistance and fretting corrosion product cytocompatibility of
      ferritic stainless steel.
AB  - To avoid nickel ion release from SUS317L as an implant material, a new type of
      nickel, commercially free, of high purity, and high chromium ferritic stainless
      steel, was developed. The new stainless steel (FJ) was studied for aspects of
      fretting corrosion and cytocompatibility compared with SUS317L. A pin-on-plate
      fretting corrosion test in an artificial physiologic solution, and cell culture
      in media with the addition of the artificial physiologic solution used for
      fretting was conducted. Resistance to the fretting induced crevice corrosion of
      FJ was higher than that of SUS317L because of the favorable electrochemical
      stability of the FJ alloy. The amount of iron ion or colloidal fine particles
      released from FJ was about a quarter of that from SUS317L, although the weight
      loss of a pin of FJ was almost 5/3 that of SUS317L. The artificial physiologic
      solution used for SUS317L fretting was more harmful to the growth of L929 and
      MC3T3-E1 cells than that used for FJ fretting. FJ was therefore superior to
      SUS317L as a biomaterial, judging from the resistance to fretting-induced crevice
      corrosion, electrochemical stability, and the cytocompatibility of fretting
      corrosion products.

PMID- 8978648
TI  - Effect of atmosphere on phase transformation in plasma-sprayed hydroxyapatite
      coatings during heat treatment.
AB  - The purpose of this study was to evaluate the effect of atmosphere on the phase
      transformation in hydroxyapatite (HA) coatings during heat treatment by varying
      the atmosphere in the furnace pipe. Heat treatment always increased the
      crystallinity of HA coatings regardless of the kind of atmosphere. Water
      molecules in atmosphere further promoted HA recrystallization during heat
      treatment. In a dry atmosphere, tricalcium phosphate (TCP) and tetracalcium
      phosphate (TTCP) were more stable than HA, so heat treatment could not convert
      them into HA. However, in a humid atmosphere, heat treatment would transform TCP
      and TTCP into HA by hydrolytic reactions.

PMID- 8978649
TI  - Use of chitosan as a biomaterial: studies on its safety and hemostatic potential.
AB  - Chitosan, a mucopolysaccharide of marine origin, was studied for its safety and
      hemostatic potential. Its surface was treated with glutaraldehyde, carbodiimide,
      and plasma glow discharge to elicit effects of enzyme degradation. Of the seven
      enzymes used, leucine amino peptidase caused maximum degradation. Autoclaving
      appeared to be an ideal sterilizing method as it caused least decrease in tensile
      strength and effected a negligible rate of hemolysis. Sterilizing with
      glutaraldehyde with a physiologic pH retained the maximum tensile strength of
      chitosan. In vivo toxicity tests indicated that it is nontoxic, and the
      sterilized films were free of pyrogen. Coagulation and hemagglutination tests
      showed that the hemostatic mechanism of chitosan seems to be independent of the
      classical coagulation cascade and appears to be an interaction between the cell
      membrane of erythrocytes and chitosan.

PMID- 8978650
TI  - Effects of metal ions on osteoblast-like cell metabolism and differentiation.
AB  - The objective of this study was to evaluate the effects of metal ions, which may
      be released from orthopedic or dental implants, on osteoblast metabolism and
      differentiation. ROS 17/2.8 cells were cultured in F-12 medium for 7 days. Then
      Al+3, Co+2, Cr+3, Ni+2, Ti+4, and V+3 were added at concentrations less than
      their cytotoxic concentrations. After 3 days, DNA synthesis, succinate
      dehydrogenase activity, alkaline phosphatase (ALP) activity, and culture
      calcification were assessed. Northern blots were performed for ALP, osteocalcin
      (OCN), and osteopontin (OPN) mRNA transcription. The data indicated that Cr+3 and
      A1+3 had few inhibitory effects on ROS cell metabolism below their cytotoxic
      concentrations, Ni+2, Co+2, Ti+4, and V+3 affected all these parameters of ROS
      cell metabolism at concentrations below cytotoxic levels. For RNA analysis, A1+3
      significantly suppressed the expression of ALP, OCN, and OPN at both cytotoxic
      and noncytoxic concentrations. Co+2 specifically suppressed ALP expression at
      cytotoxic concentrations. Cr+3 and Ni+2 inhibited OCN, OPN, and ALP gene
      expression only at cytotoxic concentrations. For Ti+4 and V+3 ions, gene
      expression at cytotoxic levels was not significantly affected as compared with
      the effects at noncytotoxic level. These results show that metal ions may alter
      osteoblast behavior even at subtoxic concentrations, but do not always affect the
      expression of all genes similarly.

PMID- 8978651
TI  - Properties of epsilon-caprolactone/DL-lactide (epsilon-CL/DL-LA) copolymers with
      a minor epsilon-CL content.
AB  - In this study the properties of DL-lactide (DL-LA) copolymers with 5, 10, 15, 20,
      and 30 wt % (in feed) of epsilon-caprolactone (epsilon-CL) polymerized with
      stannous(II)octoate (SnOct) as catalyst and glycerol, laurylalcohol, or
      pentaerythritol as initiator were investigated. Thermal studies showed that the
      addition of 5 wt % (in feed) of epsilon-CL to the P(CL/DL-LA) copolymer decreased
      the Tg by about 5 degrees C. Hydrolysis tests were carried out for copolymers
      with 20 and 30 wt % (in feed) of epsilon-CL to study the degradation rate.
      Molecular weights decreased dramatically during the first week of hydrolysis,
      with mass losses occuring a few weeks later. The influence of glycerol and
      pentaerythritol as initiators, and the influence of epsilon-CL content on stress
      strain behavior, tension set, and rheologic properties of the P(CL/DL-LA)
      copolymers were also investigated. The tensile testing of P(CL/DL-LA) copolymers
      containing 5, 10, 15, 20 wt % (in feed) of epsilon-CL showed that the properties
      of copolymers varied from hard and brittle to rubbery. The permanence of elastic
      properties was investigated with tension set measurements. These studies showed
      that copolymers crept remarkably under stress. The viscosity and elasticity of
      P(CL/DL-LA) copolymers at 120 degrees C were investigated using rheology studies.

PMID- 8978652
TI  - Investigation into the release of bioactive recombinant human growth hormone from
      normal and low-viscosity poly(methylmethacrylate) bone cements.
AB  - Previous studies showed that recombinant human growth hormone (hGH) released from
      hormone-loaded poly(methylmethacrylate) (PMMA) cement stimulated osteoid
      formation in a rabbit model. Local delivery of hGH from cemented hip
      arthroplasties may thereby provide a means of reducing the problem of aseptic
      loosening. We have investigated two different formulations of PMMA as delivery
      systems for bioactive hGH. The bioactivity of the hormone release in vitro was
      monitored with an eluted stain assay (ESTA). The hGH was also measured by an
      immunoassay, which provides an alternative assessment of structural integrity of
      the hormone released. In addition, we adapted the ESTA bioassay to assess the in
      vitro cytotoxicity of the cements. Using unloaded cements, the undiluted eluates
      from both types of PMMA proved cytotoxic. This cytotoxicity could be diluted out,
      and the procedure allowed us to measure the bioactivity of hGH in the eluates
      from hormone-loaded cements independent of their cytotoxicity. The major fraction
      of the bioactivity was released from both of the PMMA cements during the first 24
      h, but the hormone remained detectable in eluates collected after 36 days of
      elution. Comparison of the bio- and immunoactivity of the hGH released showed
      that the ratio of these two activities (i.e., the B:I ratio) was constant over
      this time period. However in parallel studies in which hormone-loaded discs were
      stored under dry conditions prior to elution, we found that the B:I ratio then
      declined markedly. This suggests that fully hydrated conditions, such as when the
      discs are bathed in assay medium, are necessary to maintain the bioactivity of
      the hGH. Both cements released only approximately 1% of the hormone originally
      incorporated, but the hGH concentration which accumulated in the eluates were
      high in physiologic terms (approximately 1000 mU/L).

PMID- 8978653
TI  - Separation and characterization of polyethylene wear debris from synovial fluid
      and tissue samples of revised knee replacements.
AB  - A study was made of in vivo-generated polyethylene wear particles as separated
      from synovial fluid samples and from tissue samples surrounding total knee
      arthroplasty. A comparison of particle size and morphology between the two
      particle groups was made to assess any effects of selective tissue capture, and
      macrophage encapsulation and digestion. In addition, a Raman spectroscopy
      technique was evaluated that enables positive identification of individual wear
      particles. The particles of the same size range found in the synovial fluid and
      tissue samples exhibited a comparable morphology. Notably, submicron-sized debris
      was present in both the synovial fluid and tissue samples surrounding knees with
      osteolysis. The novel micro-Raman analysis of individual particles was successful
      in the categorizing of wear debris as polyethylene or nonpolyethylene.

PMID- 8978654
TI  - Maturation-dependent repair of untreated osteochondral defects in the rabbit knee
      joint.
AB  - Repair of untreated full-thickness cartilage defects in the medial femoral knee
      condyle was studied in 17 young, 21 adolescent, and 19 adult rabbits. At 6 weeks,
      the defect was completely filled by tissue regeneration in all young and
      adolescent animals, but in only few of the adults (p < 0.05). The morphology of
      all repairs improved from fibrous tissue to hyaline-like cartilage over time (p <
      0.05), but at 3 and 6 weeks, the repair tissue in young and adolescent rabbits
      was more cartilage-like than in the adults (p < 0.05). In addition, bonding of
      the repair tissue to the adjacent cartilage was better in the young and
      adolescent than in the adult animals (p < 0.05). At 12 weeks, subchondral bone
      had formed in some young and adolescent repairs, but in no case in the adults.
      None of the repairs showed normal cartilage appearance, but formation of hyaline
      like cartilage was common at 12 weeks. Irrespective of age or observation time,
      the repair site showed decreased stiffness and larger strain values compared to
      adjacent or control cartilage (p < 0.001) with no tendency for improvement over
      time. Younger animals showed a faster filling of the defect and an earlier
      specialization of the repair tissue than adult animals, but the mechanical
      quality of the regenerated tissue remained inferior to normal.

PMID- 8978655
TI  - An in vivo study of the biodegradation of the hydrophilic Mitrathane.
AB  - The present study analyzes the kinetics of the in vivo degradation of hydrophilic
      Mitrathane in the peritoneal cavity of mice over a period ranging from 1 to 180
      days. The mechanical milling of the polyurethane films produced regularly
      flattened fragments that in vivo spontaneously oriented into piles. The
      morphological observations and analysis with the aid of an image analysis system
      demonstrated that after seven days of swelling the polymer fragments undergo a
      continuous degradation that leads to an irregular thinning and phagocytosis of
      the smaller fragments by macrophages with very little chronic inflammation
      response from surrounding tissues.

PMID- 8978656
TI  - The bone-bonding polymer Polyactive 80/20 induces hydroxycarbonate apatite
      formation in vitro.
AB  - The bone-bonding polymer known as Polyactive is a block copolymer composed of a
      polyethylene oxide (PEO) soft segment and a polybutylene terephthalate (PBT) hard
      segment. This study focuses on the in vitro induction of hydroxyapatite by
      Polyactive. Our results show that Polyactive is capable of inducing
      hydroxycarbonate apatite (HCAp) formation from a metastable calcium phosphate
      solution analogous to a physiological solution. In a 4-day incubation, the HCAp
      formation extended approximately 100 microm deep from the surface. A great number
      of globules about 1 microm large were found in the calcified Polyactive. These
      globules were composed of HCAp crystals embedded in the polymer matrix. There
      were so many globules in the surface that they connected with each other and
      formed a calcified layer. Next to the calcified layer was a zone where the
      globules were scattered. The calcified surface may have acted to promote HCAp
      growth from the solution, bringing about the formation of a HCAp layer on top of
      the calcified layer. The transition of solid Polyactive into a Polyactive
      hydrogel in calcium phosphate solution permitted HCAp formation within the
      polymer. It is proposed that the COOH groups produced during hydrolysis of
      Polyactive play an important role in nucleating hydroxyapatite. A remarkable
      affinity of the PEO segment of the polymer for calcium ions may facilitate moving
      calcium and phosphate from the solution into the polymer for the growth of HCAp.

PMID- 8978657
TI  - Retinal pigment epithelium cells cultured on synthetic biodegradable polymers.
AB  - Alterations in the normal structure or functions of retinal pigment epithelium
      (RPE) can result in a number of ocular diseases. Implantation of RPE cells
      cultured on thin, biodegradable polymer films may provide a means of
      transplanting an organized sheet of RPE cells with distinct apical/basal
      characteristics for the restoration of normal RPE function. We have investigated
      the interactions of human RPE cells with different biodegradable polymer films to
      assess their suitability as substrates for RPE culture. Four biodegradable
      polymers were used: low molecular weight (MW) 50:50 poly(DL-lactic-co-glycolic
      acid) (PLGA); high MW 50:50 PLGA; 75:25 PLGA; and poly(L-lactic acid) (PLLA).
      Polymer film substrates were manufactured using a solvent casting technique.
      Human fetal RPE cells (10-16 weeks gestational) were plated on the polymer
      substrates and the cultures assessed with respect to cell attachment and
      proliferation. Histological and immunohistochemical studies were performed on the
      cells after 8 days in culture. RPE cells attached to all the polymers studied
      after 8 h in culture. After 8 h, 80.2 +/- 9.5% and 82.3 +/- 7.9% of the plated
      cells were attached to substrates of high MW 50:50 PLGA and 75:25 PLGA,
      respectively. The cells proliferated on all substrates, and there was about a
      threefold increase in cell number over the 8-day culture period on all the
      polymers studied. Immunohistochemistry after 8 days in culture demonstrated RPE
      cells labeled with a distinct reaction product for cytokeratin in the cell
      cytoplasm. All the polymers studied were suitable for RPE culture; however, high
      MW 50:50 PLGA and 75:25 PLGA proved to be the best in terms of manufacturing
      properties, cell attachment, and proliferation. These polymers can provide a
      suitable substrate for RPE cell culture and hold promise for the subretinal
      implantation of organized sheets of RPE cells.

PMID- 8978658
TI  - Development and characterization of a biodegradable polyphosphate.
AB  - A biodegradable polyphosphate polymer (Mn = 18,000, Mw/Mn = 3.2) matrix system
      was developed as a potential delivery vehicle for growth factors. As a model
      system, release of recombinant human osteogenic protein-1 (OP-1) from this
      polymer was evaluated. The polyphosphate was synthesized using a triethylamine
      catalyst in an argon environment, and characterized using elemental analysis, gel
      permeation chromatography (GPC), and Fourier transform infrared spectroscopy
      (FTIR). Degradation kinetics of the polyphosphate polymer in phosphate-buffered
      saline (PBS) were represented by a second-order polynomial while degradation in
      bovine serum was linear with time. The polymer degraded faster in PBS than in
      bovine serum. In vitro release of OP-1 was also faster in PBS than in serum.
      Release kinetics of OP-1 in PBS and serum were represented by second-order
      polynomials. The OP-1 release from this physically dispersed polymeric matrix may
      be described by several possible mechanisms: diffusion, bulk polymer degradation,
      ion complexation, and interactions among the protein (OP-1), polymer, proteins,
      and enzymes in the media. This polyphosphate may be an effective carrier for
      morphogens, growth factors, or other classes of bioactive molecules.

PMID- 8978659
TI  - Plasma protein adsorption and platelet adhesion onto comb-like PEO gradient
      surfaces.
AB  - Comb-like polyethylene oxide (PEO) surfaces were prepared on low-density
      polyethylene (PE). The comb-like PEO chain density was changed gradually along
      the sample lengths by corona discharge treatment with gradually increasing power
      and the following graft copolymerization of poly(ethylene glycol)
      monomethacrylate macromers (PEO-MA). The macromers with different PEO repeat
      unit, 1, 5, and 10, were used. The prepared comb-like PEO gradient surfaces were
      characterized by water contact angle, Fourier transform infrared spectroscopy in
      the attenuated total reflectance mode, and electron spectroscopy for chemical
      analysis. All these measurements indicated that the PEO chains are grafted on the
      PE surface with gradually increasing density of PEO. Plasma protein adsorption
      and platelet adhesion on the PEO gradient surfaces decreased with increasing PEO
      chain length and surface density. As observed by scanning electron microscopy,
      PEO10-MA-grafted surface with high PEO density was very effective in preventing
      protein adsorption and platelet adhesion and did not activate the platelets.

PMID- 8978660
TI  - LPS increases biomaterial degradation by human monocytes in vitro.
AB  - Different cell lines are involved during an immunological reaction, principally
      lymphocytes and monocytes. Monocyte/macrophage cells, which are among the first
      to appear in wound-healing and infection sites, are largely implicated in
      phagocytosis and could be involved in calcium-phosphate degradation. Their role
      in these processes may relate to cytokine secretions and/or their sensitivity to
      certain cytokines. We tested the behavior of human monocytes placed on the
      surface of biphasic calcium-phosphate (BCP) tablets in the presence of two
      lipopolysaccharide (LPS) concentrations. After short-term culture (48 h),
      cytokine release (IL-1beta, IL-6) was measured by ELISA, and morphological cell
      events and biomaterial degradation were observed in scanning electron microscopy.
      BCP surface pits were noted near cells stimulated by 0.5 microg/mL LPS but were
      not apparent with 10 microg/mL LPS. The number of lacunae on BCP was increased
      after LPS treatment of human monocytes. An upmodulation of IL-1beta and IL-6 (in
      culture medium) released by LPS-activated human monocytes was observed,
      indicating good cell stimulation. This study demonstrates that LPS-activated
      human monocytes can degrade the surface of calcium-phosphate ceramic and confirms
      the role of human monocytes in biomaterial degradation.

PMID- 8978661
TI  - The effect of Ca-P plasma-sprayed coatings on the initial bone healing of oral
      implants: an experimental study in the goat.
AB  - The response of bone of low density to uncoated, fluorapatite (FA),
      hydroxyapatite (HA), and hydroxyapatite heat treated (HAHT) plasma-sprayed coated
      implants was investigated 3 and 6 months after installation. Forty-eight threaded
      implants of commercially pure titanium were inserted into the maxilla of twelve
      goats according to a split-plot design. One goat died shortly after installation
      of the implants, five goats were sacrificed 3 months after installation, and the
      other six goats 6 months after installation. Histological evaluation revealed no
      difference in bone reaction between the 3- and 6-month implantation periods. In
      addition, probably due to the wide inter- and intra-animal variability, no
      significant difference between the 3- and the 6-month periods could be observed
      in the histomorphometrical measurements performed. Further, no significant
      differences were found in bone reaction among the various implant materials.
      Finally, qualitatively it appeared that all coatings showed reduction in coating
      thickness and that such reductions were most pronounced for the HA coatings.

PMID- 8978662
TI  - Application of tertiary amines with reduced toxicity to the curing process of
      acrylic bone cements.
AB  - 4-Dimethylaminobenzyl alcohol (DMOH) and 4-dimethylaminobenzyl methacrylate
      (DMMO) were used as the activators in the benzoyl peroxide initiated redox
      polymerization for the preparation of acrylic bone cement based on
      poly(methylmethacrylate) beads of different particle size. The residual monomer
      content of the cured cements was about 2 wt %, independent of the redox system
      used in the polymerization, indicating that the activating effect of the tertiary
      aromatic amines DMOH or DMMO was sufficient to reach a polymerization conversion
      similar to that obtained with the benzoyl peroxide (BPO) N,N-dimethyl-4-toluidine
      (DMT) system. The BPO/DMOH and BPO/DMMO redox systems provided exotherms of
      decreasing peak temperature and increasing setting time, and the cured materials
      presented higher average molecular weight and similar glass transition
      temperatures in comparison with those obtained when DMT was used as the
      activator. In addition, these activators are three times less toxic than the
      classical DMT.

PMID- 8978663
TI  - Chemical chaperones interfere with the formation of scrapie prion protein.
AB  - The fundamental event in prion diseases involves a conformational change in one
      or more of the alpha-helices of the cellular prion protein (PrP(C)) as they are
      converted into beta-sheets during the formation of the pathogenic isoform
      (PrP(Sc)). Here, we show that exposure of scrapie-infected mouse neuroblastoma
      (ScN2a) cells to reagents known to stabilize proteins in their native
      conformation reduced the rate and extent of PrP(Sc) formation. Such reagents
      include the cellular osmolytes glycerol and trimethylamine N-oxide (TMAO) and the
      organic solvent dimethylsulfoxide (DMSO), which we refer to as 'chemical
      chaperones' because of their influence on protein folding. Although the chemical
      chaperones did not appear to affect the existing population of PrP(Sc) molecules
      in ScN2a cells, they did interfere with the formation of PrP(Sc) from newly
      synthesized PrP(C). We suggest that the chemical chaperones act to stabilize the
      alpha-helical conformation of PrP(C) and thereby prevent the protein from
      undergoing a conformational change to produce PrP(Sc). These observations provide
      further support for the idea that prions arise due to a change in protein
      conformation and reveal potential strategies for preventing PrP(Sc) formation.

PMID- 8978664
TI  - The plastocyanin binding domain of photosystem I.
AB  - The molecular recognition between plastocyanin and photosystem I was studied.
      Photosystem I and plastocyanin can be cross-linked to an active electron transfer
      complex. Immunoblots and mass spectrometric analysis of proteolytic peptides
      indicate that the two negative patches conserved in plant plastocyanins are cross
      linked with lysine residues of a domain near the N-terminus of the PsaF subunit
      of photosystem I. Conversion of these negative to uncharged patches of
      plastocyanin by site-directed mutation D42N/E43Q/D44N/E45Q and E59Q/E60Q/D61N
      respectively, reveals the first patch to be essential for the electrostatic
      interaction in the electron transfer complex with photosystem I and the second
      one to lower the redox potential. The domain in PsaF, not found in cyanobacteria,
      is predicted to fold into two amphipathic alpha-helices. The interacting N
      terminal helix lines up six lysines on one side which may guide a fast one
      dimensional diffusion of plastocyanin and provide the electrostatic attraction at
      the attachment site, in addition to the hydrophobic interaction in the area where
      the electron is transferred to P700 in the reaction center of photosystem I. This
      two-step interaction is likely to increase the electron transfer rate by more
      than two orders of magnitude in plants as compared with cyanobacteria. Our data
      resolve the controversy about the function of PsaF.

PMID- 8978665
TI  - Expression and function of TrkB variants in developing sensory neurons.
AB  - Mouse trigeminal neurons survive independently of neurotrophins when their axons
      are growing to their targets, and are then transiently supported by BDNF before
      becoming NGF dependent. During the stage of neurotrophin independence,
      transcripts encoding the BDNF receptor, TrkB, were expressed at very low levels.
      During the stage of BDNF dependence, high levels of a transcript encoding a
      receptor with the catalytic tyrosine kinase domain were expressed. Although the
      levels of this transcript fell as the neurons lost responsiveness to BDNF, there
      were concomitant increases in the expression of transcripts encoding TrkB
      variants lacking the kinase domain. Analysis of RNA from purified neurons showed
      that all of these transcripts were present in neurons. BDNF and NGF up-regulated
      the expression of these transcripts early in development but had little effect
      later on. To test whether truncated TrkB modulates BDNF signalling via catalytic
      TrkB, we injected TrkB expression plasmids into NGF-dependent sympathetic
      neurons. Whereas expression of catalytic TrkB alone conferred a BDNF survival
      response, co-expression of non-catalytic TrkB substantially reduced this
      response. Our results suggest that BDNF responsiveness in sensory neurons during
      development is modulated by the relative levels of catalytic and non-catalytic
      TrkB.

PMID- 8978666
TI  - Control of neural precursor specification by proneural proteins in the CNS of
      Drosophila.
AB  - Formation of neural precursors in Drosophila is determined by proneural genes.
      The distinctive pattern of expression of some genes of the achaete-scute complex
      in the embryonic neuroectoderm has prompted the speculation that they could also
      function in the specification of neural precursor identity in the CNS. To test
      this hypothesis, we have analysed the capacity of different proneural proteins to
      promote the development of a particular CNS precursor, the MP2 precursor. Our
      results indicate that: (i) all known proneural proteins are similarly able to
      support the formation of a neural precursor at the position of MP2; (ii)
      different proneural proteins promote the expression of different characteristics
      of MP2; and (iii) a totally normal specification of the MP2 fate can only be
      attained by the proneural genes achaete or scute.

PMID- 8978667
TI  - Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge.
AB  - TWIK-1 is a new type of K+ channel with two P domains and is abundantly expressed
      in human heart and brain. Here we show that TWIK-1 subunits can self-associate to
      give dimers containing an interchain disulfide bridge. This assembly involves a
      34 amino acid domain that is localized to the extracellular M1P1 linker loop.
      Cysteine 69 which is part of this interacting domain is implicated in the
      formation of the disulfide bond. Replacing this cysteine with a serine residue
      results in the loss of functional K+ channel expression. This is the first
      example of a covalent association of functional subunits in voltage-sensitive
      channels via a disulfide bridge.

PMID- 8978668
TI  - TolA central domain interacts with Escherichia coli porins.
AB  - TolA is an inner membrane protein with three domains: a transmembrane N-terminus
      and periplasmic central and C-terminal domains. The interaction of TolA with
      outer membrane porins of Escherichia coli was investigated. Western blot analyses
      of cell extracts with anti-TolA antibodies indicated that TolA forms high
      molecular weight complexes specifically with trimeric OmpF, OmpC, PhoE and LamB,
      but not with OmpA. The interaction of purified TolA domains with purified porins
      was also studied. TolA interacted with OmpF, PhoE and LamB porins via its central
      domain, but not with either their denatured monomeric forms or OmpA. Moreover,
      the presence or absence of lipopolysaccharides associated with trimeric porins
      did not modify the interactions. These results suggest that the specific
      interaction of TolA with outer membrane porins might be relevant to the function
      of Tol proteins.

PMID- 8978669
TI  - Targeted mutagenesis of acyl-lipid desaturases in Synechocystis: evidence for the
      important roles of polyunsaturated membrane lipids in growth, respiration and
      photosynthesis.
AB  - Acyl-lipid desaturases introduce double bonds (unsaturated bonds) at specifically
      defined positions in fatty acids that are esterified to the glycerol backbone of
      membrane glycerolipids. The desA, desB and desD genes of Synechocystis sp. PCC
      6803 encode acyl-lipid desaturases that introduce double bonds at the delta12,
      omega3 and delta6 positions of C18 fatty acids respectively. The mutation of each
      of these genes by insertion of an antibiotic resistance gene cartridge completely
      eliminated the corresponding desaturation reaction. This system allowed us to
      manipulate the number of unsaturated bonds in membrane glycerolipids in this
      organism in a step-wise manner. Comparisons of the variously mutated cells
      revealed that the replacement of all polyunsaturated fatty acids by a
      monounsaturated fatty acid suppressed growth of the cells at low temperature and,
      moreover, it decreased the tolerance of the cells to photoinhibition of
      photosynthesis at low temperature by suppressing recovery of the photosystem II
      protein complex from photoinhibitory damage. However, the replacement of tri- and
      tetraunsaturated fatty acids by a diunsaturated fatty acid did not have such
      effects. These findings indicate that polyunsaturated fatty acids are important
      in protecting the photosynthetic machinery from photoinhibition at low
      temperatures.

PMID- 8978670
TI  - Fission yeast Sop2p: a novel and evolutionarily conserved protein that interacts
      with Arp3p and modulates profilin function.
AB  - Profilins bind to monomeric actin and also interact with ligands such as
      phosphoinositide 4,5-bisphosphate, the proline-rich protein VASP and a complex of
      four to six polypeptides identified in Acanthamoeba that includes two actin
      related proteins. Here, we report the identification and characterization of an
      essential gene from Schizosaccharomyces pombe, sop2+, a mutation in which rescues
      the temperature-sensitive lethality of a profilin mutation, cdc3-124. The sop2-1
      mutant is defective for cell elongation and septation, suggesting that it is
      involved in multiple cortical actin-requiring processes. Consistent with a role
      in actin cytoskeletal function, negative interactions have been identified
      between sop2-1 and act1-48, a mutant allele of actin. Sop2p is a novel 377 amino
      acid polypeptide with similarity to proteins of the beta-transducin repeat
      family. Sop2p-related proteins have been identified by sequencing projects in
      diverse species, and we have isolated a human cDNA highly related to sop2+, SOP2
      Hs, which functionally complements the sop2-1 mutation. Sop2p proteins from all
      species contain peptide sequences identical or highly similar to two peptide
      sequences from an Acanthamoeba beta-transducin repeat protein present in the
      profilin binding complex. Biochemical analyses demonstrate that Sop2p is present
      in a complex which also contains the actin-related protein, Arp3p.
      Immunofluorescence studies reveal the presence of Sop2p in (i) punctate
      structures distributed throughout the cell, (ii) cables that extend the length of
      the cell, and (iii) a medial band in a small percentage of septating cells.
      Collectively these data demonstrate the interaction of Sop2p with Arp3p, profilin
      and actin.

PMID- 8978671
TI  - The Schizosaccharomyces pombe actin-related protein, Arp3, is a component of the
      cortical actin cytoskeleton and interacts with profilin.
AB  - The gene encoding the actin-related protein Arp3 was first identified in the
      fission yeast Schizosaccharomyces pombe and is a member of an evolutionarily
      conserved family of actin-related proteins. Here we present several key findings
      that define an essential role for Arp3p in the functioning of the cortical actin
      cytoskeleton. First, mutants in arp3 interact specifically with profilin and
      actin mutants. Second, Arp3 localizes to cortical actin patches which are
      required for polarized cell growth. Third, the arp3 gene is required for the
      reorganization of the actin cytoskeleton during the cell cycle. Finally, the Arp3
      protein is present in a large protein complex. We believe that this complex may
      mediate the cortical functions of profilin at actin patches in S. pombe.

PMID- 8978672
TI  - Kes1p shares homology with human oxysterol binding protein and participates in a
      novel regulatory pathway for yeast Golgi-derived transport vesicle biogenesis.
AB  - The yeast phosphatidylinositol transfer protein (Sec14p) is required for
      biogenesis of Golgi-derived transport vesicles and cell viability, and this
      essential Sec14p requirement is abrogated by inactivation of the CDP-choline
      pathway for phosphatidylcholine biosynthesis. These findings indicate that Sec14p
      functions to alleviate a CDP-choline pathway-mediated toxicity to yeast Golgi
      secretory function. We now report that this toxicity is manifested through the
      action of yeast Kes1p, a polypeptide that shares homology with the ligand-binding
      domain of human oxysterol binding protein (OSBP). Identification of Kes1p as a
      negative effector for Golgi function provides the first direct insight into the
      biological role of any member of the OSBP family, and describes a novel pathway
      for the regulation of Golgi-derived transport vesicle biogenesis.

PMID- 8978673
TI  - Two GTPase isoforms, Ypt31p and Ypt32p, are essential for Golgi function in
      yeast.
AB  - In eukaryotic cells, monomeric GTPases of the Ypt/Rab family function as
      regulators at defined steps of vesicular transport in exo- and endocytosis. Here
      we report on the isolation and characterization of two genes (YPT31 and YPT32) of
      the yeast Saccharomyces cerevisiae which encode members of the Ypt family
      exhibiting >80% sequence identity. Whereas the disruption of one of the two genes
      was phenotypically neutral, the disruption of both YPT31 and YPT32 led to
      lethality. Depletion of wild-type Ypt31p or of a short-lived ubiquitin-Ypt31p in
      a ypt32 null background led to a massive accumulation of Golgi-like membranes, an
      inhibition of invertase secretion and defects in vacuolar protein maturation.
      Similar alterations were observed in a conditional-lethal ypt31-1 mutant at 30
      min after shift to the non-permissive temperature. According to subcellular
      fractionation, a significant part of Ypt31p appeared to be located in Golgi
      enriched membrane fractions. In accordance with this, indirect immunofluorescence
      using affinity-purified anti-Ypt31p antibodies gave a punctate staining similar
      to that observed with Golgi-located proteins. From the phenotypic alterations
      observed in ypt31 and ypt32 mutants, it seems likely that the two GTPases are
      involved in intra-Golgi transport or in the formation of transport vesicles at
      the most distal Golgi compartment.

PMID- 8978674
TI  - Rho guanine nucleotide dissociation inhibitor protein (RhoGDI) inhibits
      exocytosis in mast cells.
AB  - Introducing non-hydrolysable analogues of GTP into the cytosolic compartment of
      mast cells results in exocytotic secretion through the activation of GTP binding
      proteins. The identity and mechanism of action of these proteins are not
      established. We have investigated the effects of Rho GDP dissociation inhibitor
      (RhoGDI) on exocytosis induced by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma
      S) in rat mast cells, introducing the protein into cells by means of a patch
      pipette and recording the progress of exocytosis by monitoring cell capacitance.
      To allow time for the protein to enter the cells and find its correct location,
      stimulation was provided 5-10 min after patch rupture by photolysing caged GTP
      gamma-S included in the pipette solution. When bovine RhoGDI was introduced into
      mast cells, exocytosis was inhibited at concentrations of 200-400 nM for native
      protein and 800 nM to 8 microM for the recombinant form. Protein denatured by
      heat or N-ethylmaleimide treatment did not inhibit. In permeabilized cells,
      recombinant RhoGDI increased the rate at which cells lose their ability to
      respond to GTP-gamma-S. These data demonstrate that one or more small GTP binding
      proteins of the Rho family has a central role in the exocytotic mechanism in mast
      cells.

PMID- 8978675
TI  - The Exocyst is a multiprotein complex required for exocytosis in Saccharomyces
      cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, the products of at least 15 genes are
      involved specifically in vesicular transport from the Golgi apparatus to the
      plasma membrane. Previously, we have shown that three of these genes, SEC6, SEC8
      and SEC15, encode components of a multisubunit complex which localizes to the tip
      of the bud, the predominant site of exocytosis in S. cerevisiae. Mutations in
      three more of these genes, SEC3, SEC5 and SEC10, were found to disrupt the
      subunit integrity of the Sec6-Sec8-Sec15 complex, indicating that these genes may
      encode some of the remaining components of this complex. To examine this
      possibility, we cloned and sequenced the SEC5 and SEC10 genes, disrupted them,
      and either epitope tagged them (Sec5p) or prepared polyclonal antisera (Sec10p)
      to them for co-immunoprecipitation studies. Concurrently, we biochemically
      purified the remaining unidentified polypeptides of the Sec6-Sec8-Sec15 complex
      for peptide microsequencing. The genes encoding these components were identified
      by comparison of predicted amino acid sequences with those obtained from peptide
      microsequencing of the purified complex components. In addition to Sec6p, Sec8p
      and Sec15p, the complex contains the proteins encoded by SEC3, SEC5, SEC10 and a
      novel gene, EXO70. Since these seven proteins function together in a complex
      required for exocytosis, and not other intracellular trafficking steps, we have
      named it the Exocyst.

PMID- 8978676
TI  - Preformed cytoplasmic nucleocapsids are not necessary for alphavirus budding.
AB  - According to the present model for assembly of alphaviruses, e.g. Semliki Forest
      virus (SFV), the viral genome is first encapsidated into a nucleocapsid (NC) in
      cytoplasm and this is then used for budding at plasma membrane (PM). The
      preformed NC is thought to act as a template on which the viral envelope can be
      organized. In the present work we have characterized two SFV deletion mutants
      which did not assemble NCs in the cytoplasm but which instead appeared to form
      NCs at the PM simultaneously with virus budding. The deletions were introduced in
      a conserved 14 residue long linker peptide that joins the amino-terminal RNA
      binding domain with the carboxy-terminal serine-protease domain of the capsid
      protein. Despite the deletions and the change in morphogenesis, wild-type (wt)
      like particles were produced with almost wt efficiency. It is suggested that the
      NC assembly defect of the mutants is rescued through spike-capsid interactions at
      PM. The results show that the preassembly of NCs in the cytoplasm is not a
      prerequisite for alphavirus budding. The apparent similarities of the
      morphogenesis pathways of wt and mutant SFV with those of type D and type C
      retroviruses are discussed.

PMID- 8978677
TI  - Uncoupling of stem cell inhibition from monocyte chemoattraction in MIP-1alpha by
      mutagenesis of the proteoglycan binding site.
AB  - We have studied the role of proteoglycans in the function of Macrophage
      Inflammatory Protein-1 alpha (MIP-1alpha), a member of the proteoglycan binding
      chemokine family. Sequence and peptide analysis has identified a basic region
      within MIP-1alpha which appears to be the major determinant of proteoglycan
      binding and we have now produced a mutant of MIP-1alpha lacking the basic charges
      on two of the amino acids within this proteoglycan binding site. This mutant (Hep
      Mut) appears to have lost the ability to bind to proteoglycans. Bioassay of Hep
      Mut indicates that it has retained stem cell inhibitory properties but has a
      compromised activity as a monocyte chemoattractant, thus suggesting uncoupling of
      these two properties of MIP-1alpha. Receptor studies have indicated that the
      inactivity of Hep Mut on human monocytes correlates with its inability to bind to
      CCR1, a cloned human MIP-1alpha receptor. In addition, studies using proteoglycan
      deficient cells transfected with CCR1 have indicated that the proteoglycan
      binding site in MIP-1alpha is a site that is also involved in the docking of MIP
      1alpha to the monocyte receptor. The site for interaction with the stem cell
      receptor must therefore be distinct, suggesting that MIP-1alpha utilizes
      different receptors for these two different biological processes.

PMID- 8978678
TI  - Aggregation-dependent, integrin-mediated increases in cytoskeletally associated
      PtdInsP2 (4,5) levels in human platelets are controlled by translocation of
      PtdIns 4-P 5-kinase C to the cytoskeleton.
AB  - Thrombin-stimulated aggregation of human platelets promotes an increase in the
      phosphatidylinositol 4-phosphate (PtdIns 4-P) 5-kinase (PIPkin) activity in the
      cytoskeleton. This phenomenon is associated with translocation of PIPkin isoform
      C to the cytoskeleton and with an increase in the amount of phosphatidylinositol
      bisphosphate (PtdInsP2) bound to the cytoskeletal pellet. All three of these
      effects are prevented if the platelets are not stirred or if RGD-containing
      peptides are present, demonstrating that they require integrin activation. All
      three are also abolished by pretreatment with okadaic acid, which also prevents
      the aggregation-dependent translocation of pp60(c-src) to the cytoskeleton. The
      results point to the existence of a cytoskeletally associated PtdInsP2 pool under
      the control of integrin-mediated signals that act via PIPkin C and suggest that a
      common, okadaic acid-sensitive mechanism may underlie the aggregation-dependent
      translocation of certain signalling molecules to the platelet cytoskeleton.

PMID- 8978679
TI  - Transformation by Rho exchange factor oncogenes is mediated by activation of an
      integrin-dependent pathway.
AB  - Constitutive activation of growth factor receptor signaling pathways leads to
      uncontrolled growth, but why tumor cells become anchorage independent is less
      clear. The fact that integrins transmit signals required for cell growth suggests
      that constitutive activation of steps downstream from integrins mediates
      anchorage independence. Since the small GTPase Rho may mediate integrin signal
      transduction, the effects of serum and the Rho nucleotide exchange factor
      oncogenes dbl and lbc on cell growth and signaling pathways were examined. Our
      data show that these oncogenes induce anchorage-independent but serum-dependent
      growth and stimulation of signaling pathways. These results show, therefore, that
      anchorage-independent growth results from constitutive activation of integrin
      dependent signaling events. They also support the view that Rho is a functionally
      important mediator of integrin signaling.

PMID- 8978680
TI  - Tyrosine-599 of the c-Mpl receptor is required for Shc phosphorylation and the
      induction of cellular differentiation.
AB  - Interaction of thrombopoietin (TPO) with its receptor, c-Mpl, triggers cell
      growth and differentiation responses controlling primitive haemopoietic cell
      production and megakaryocytopoiesis. To examine the important receptor domains
      and signal transduction pathways involved in these cellular responses, c-Mpl
      cytoplasmic domain truncation and tyrosine substitution mutants were generated.
      In the myelomonocytic leukaemia cell lines WEHI3B-D+ and M1, ectopic expression
      of the wild-type c-Mpl receptor induced TPO-dependent cellular differentiation
      characterized by increased cell migration through agar and acquisition of the
      morphology and molecular markers of macrophages. Consistent with the concept that
      proliferative and differentiation signals emanate from distinct receptor domains,
      the C-terminal 33 amino acids of c-Mpl were dispensable for a proliferative
      response in Ba/F3 cells but proved critical for WEHI3B-D+ and M1 differentiation.
      Finer mapping revealed that substitution of Tyr599 by phenylalanine within this c
      Mpl domain was sufficient to abolish the normal differentiation response.
      Moreover, in contrast to the normal c-Mpl receptor, this same mplY599F mutant was
      also incapable of stimulating TPO-dependent Shc phosphorylation, the association
      of Shc with Grb2 or c-Mpl and of inducing c-fos expression. Thus activation of
      components of the Ras signalling cascade, initiated by interaction of Shc with c
      Mpl Tyr599, may play a decisive role in specific differentiation signals
      emanating from the c-Mpl receptor.

PMID- 8978681
TI  - Mechanism of activation of protein kinase B by insulin and IGF-1.
AB  - Insulin activated endogenous protein kinase B alpha (also known as RAC/Akt
      kinase) activity 12-fold in L6 myotubes, while after transfection into 293 cells
      PKBalpha was activated 20- and 50-fold in response to insulin and IGF-1
      respectively. In both cells, the activation of PKBalpha was accompanied by its
      phosphorylation at Thr308 and Ser473 and, like activation, phosphorylation of
      both of these residues was prevented by the phosphatidylinositol 3-kinase
      inhibitor wortmannin. Thr308 and/or Ser473 were mutated to Ala or Asp and
      activities of mutant PKBalpha molecules were analysed after transfection into 293
      cells. The activity of wild-type and mutant PKBalpha was also measured in vitro
      after stoichiometric phosphorylation of Ser473 by MAPKAP kinase-2. These
      experiments demonstrated that activation of PKBalpha by insulin or insulin-like
      growth factor-1 (IGF-1) results from phosphorylation of both Thr308 and Ser473,
      that phosphorylation of both residues is critical to generate a high level of
      PKBalpha activity and that the phosphorylation of Thr308 in vivo is not dependent
      on phosphorylation of Ser473 or vice versa. We propose a model whereby PKBalpha
      becomes phosphorylated and activated in insulin/IGF-1-stimulated cells by an
      upstream kinase(s).

PMID- 8978682
TI  - The p38 and ERK MAP kinase pathways cooperate to activate Ternary Complex Factors
      and c-fos transcription in response to UV light.
AB  - We investigated the activation of c-fos transcription following UV irradiation, a
      'stress' stimulus. In both HeLa TK- and NIH 3T3 cells the Serum Response Element
      is required for efficient UV-induced c-fos transcription, and in HeLa TK- cells
      the Ternary Complex Factor (TCF) binding site contributes substantially to
      activation. Consistent with this, UV irradiation activates LexA-TCF fusion
      proteins more strongly in HeLa TK- than in NIH 3T3 cells. The TCF C-termini of
      the TCFs are substrates for UV-induced MAP kinases: both the Elk-1 and SAP-1a C
      termini are efficiently phosphorylated by the p38 MAPK, but only the Elk-1 C
      terminus is a good substrate for the SAPK/JNKs. The specificity and activation
      kinetics of TCF C-terminal kinases, and the susceptibility of transcriptional
      activation by LexA-TCF fusion proteins to specific inhibitors of different MAPK
      pathways, show that both the ERK and p38 MAPK pathways contribute to TCF
      activation in response to UV irradiation. Activity of both these pathways is also
      required for the response of the c-fos gene itself to UV stimulation.

PMID- 8978683
TI  - A novel chloride channel in Vicia faba guard cell vacuoles activated by the
      serine/threonine kinase, CDPK.
AB  - Calcium-Dependent Protein Kinases (CDPKs) in higher plants contain a C-terminal
      calmodulin-like regulatory domain. Little is known regarding physiological CDPK
      targets. Both kinase activity and multiple Ca2+-dependent signaling pathways have
      been implicated in the control of stomatal guard cell movements. To determine
      whether CDPK or other protein kinases could have a role in guard cell signaling,
      purified and recombinant kinases were applied to Vicia faba guard cell vacuoles
      during patch-clamp experiments. CDPK activated novel vacuolar chloride (VCL) and
      malate conductances in guard cells. Activation was dependent on both Ca2+ and
      ATP. Furthermore, VCL activation occurred in the absence of Ca2+ using a Ca2+
      independent, constitutively active, CDPK* mutant. Protein kinase A showed weaker
      activation (22% as compared with CDPK). Current reversals in whole vacuole
      recordings shifted with the Nernst potential for Cl-and vanished in glutamate.
      Single channel recordings showed a CDPK-activated 34 +/- 5 pS Cl- channel. VCL
      channels were activated at physiological potentials enabling Cl- uptake into
      vacuoles. VCL channels may provide a previously unidentified, but necessary,
      pathway for anion uptake into vacuoles required for stomatal opening. CDPK
      activated VCL currents were also observed in red beet vacuoles suggesting that
      these channels may provide a more general mechanism for kinase-dependent anion
      uptake.

PMID- 8978684
TI  - Yeast Gpi8p is essential for GPI anchor attachment onto proteins.
AB  - Glycosylphosphatidylinositol (GPI) anchors are added onto newly synthesized
      proteins in the ER. Thereby a putative transamidase removes a C-terminal peptide
      and attaches the truncated protein to the free amino group of the preformed GPI.
      The yeast mutant gpi8-1 is deficient in this addition of GPIs to proteins. GPI8
      encodes for an essential 47 kDa type I membrane glycoprotein residing on the
      luminal side of the ER membrane. GPI8 shows significant homology to a novel
      family of vacuolar plant endopeptidases one of which is supposed to catalyse a
      transamidation step in the maturation of concanavalin A and acts as a
      transamidase in vitro. Humans have a gene which is highly homologous to GPI8 and
      can functionally replace it.

PMID- 8978685
TI  - The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth.
AB  - Phosphoinositide 3-kinases (PI3Ks) have been identified in an evolutionarily
      diverse range of organisms, including mammals, Drosophila, yeast, plants and
      Dictyostelium. They are activated by a multitude of extracellular signals and
      implicated in mitogenesis, differentiation and cell survival, as well as in the
      control of the cytoskeleton and cell shape. Here we describe the molecular and
      functional analysis of Drosophila p110 (Dp110). A full-length Dp110 cDNA was
      isolated and found to encode a protein homologous throughout its length to the
      class I mammalian PI3Ks p110alpha and p110beta. Overexpression of Dp110 in wing
      or eye imaginal discs resulted in flies with enlarged wings or eyes respectively.
      In contrast, overexpression of Dp110 containing a mutation predicted to result in
      the loss of catalytic activity resulted in smaller wings and eyes. The
      alterations in wing size result from changes in both cell size and cell number,
      whereas in the eye only differences in cell size were detected. These data imply
      a role for Dp110 in growth control during Drosophila development and have
      implications for the function of class I PI3Ks in other organisms.

PMID- 8978687
TI  - The fission yeast dma1 gene is a component of the spindle assembly checkpoint,
      required to prevent septum formation and premature exit from mitosis if spindle
      function is compromised.
AB  - Premature initiation of cytokinesis can lead to loss of chromosomes, and
      'cutting' of the nucleus. Therefore, the proper spatial and temporal co
      ordination of mitosis and cytokinesis is essential for maintaining the integrity
      of the genome. The fission yeast cdc16 gene is implicated both in the spindle
      assembly checkpoint and control of septum formation. To identify other proteins
      involved in these controls, we have isolated multicopy suppressors of the cdc16
      116 mutation, and the characterization of one of these, dma1 (defective in
      mitotic arrest), is presented here. dma1 is not an essential gene, but in a dma1
      null background (dma1-D1) the function of the spindle assembly checkpoint is
      compromised. If assembly of the spindle is prevented, dma1-D1 cells do not
      arrest, the activity of cdc2 kinase decays and cells form a division septum
      without completing a normal mitosis. dma1-D1 cells also show an increased rate of
      chromosome loss during exponential growth. Upon ectopic expression from an
      inducible promoter, dma1p delays progress through mitosis and inhibits septum
      formation, giving rise to elongated, multinucleate cells. We propose that dma1 is
      a component of the spindle assembly checkpoint, required to prevent septum
      formation and premature exit from mitosis if spindle function is impaired.

PMID- 8978686
TI  - Growth arrest by the cyclin-dependent kinase inhibitor p27Kip1 is abrogated by c
      Myc.
AB  - We show here that c-Myc antagonizes the cyclin-dependent kinase (CDK) inhibitor
      p27Kip1. p27 expressed from recombinant retroviruses in Rat1 cells associated
      with and inhibited cyclin E/CDK2 complexes, induced accumulation of the pRb and
      p130 proteins in their hypophosphorylated forms, and arrested cells in G1. Prior
      expression of c-Myc prevented inactivation of cyclin E/CDK2 as well as
      dephosphorylation of pRb and p130, and allowed continuous cell proliferation in
      the presence of p27. This effect did not require ubiquitin-mediated degradation
      of p27. Myc altered neither the susceptibility of cyclin E/CDK2 to inhibition by
      p27, nor the intrinsic CDK-inhibitory activity of p27, but induced sequestration
      of p27 in a form unable to bind cyclin E/CDK2. Neither Myc itself nor other G1
      cyclin/CDK complexes were directly responsible for p27 sequestration. Retroviral
      expression of G1 cyclins (D1-3, E or A) or of the Cdc25A phosphatase did not
      overcome p27-induced arrest. Growth rescue by Myc required dimerization with Max,
      DNA binding and an intact transcriptional activation domain, as previously shown
      for cellular transformation. We propose that this activity is mediated by the
      product of an as yet unknown Myc-Max target gene(s) and represents an essential
      aspect of Myc's mitogenic and oncogenic functions.

PMID- 8978688
TI  - Fission yeast Cut1 and Cut2 are essential for sister chromatid separation,
      concentrate along the metaphase spindle and form large complexes.
AB  - Fission yeast Schizosaccharomyces pombe temperature-sensitive (ts) cut1 mutants
      fail to separate sister chromatids in anaphase but the cells continue to divide,
      leading to bisection of the undivided nucleus (the cut phenotype). If cytokinesis
      is blocked, replication continues, forming a giant nucleus with polyploid
      chromosomes. We show here that the phenotype of ts cut2-364 is highly similar to
      that of cut1 and that the functions of the gene products of cut1+ and cut2+ are
      closely interrelated. The cut1+ and cut2+ genes are essential for viability and
      interact genetically. Cut1 protein concentrates along the short spindle in
      metaphase as does Cut2. Cut1 (approximately 200 kDa) and Cut2 (42 kDa) associate,
      as shown by immunoprecipitation, and co-sediment as large complexes (30 and 40S)
      in sucrose gradient centrifugation. Their behavior in the cell cycle is
      strikingly different, however: Cut2 is degraded in anaphase by the same
      proteolytic machinery used for the destruction of cyclin B, whereas Cut1 exists
      throughout the cell cycle. The essential function of the Cut1-Cut2 complex which
      ensures sister chromatid separation may be regulated by Cut2 proteolysis. The C
      terminal region of Cut1 is evolutionarily conserved and similar to that of
      budding yeast Esp1, filamentous fungi BimB and a human protein.

PMID- 8978689
TI  - Requirement for PP1 phosphatase and 20S cyclosome/APC for the onset of anaphase
      is lessened by the dosage increase of a novel gene sds23+.
AB  - Ubiquitin-dependent proteolysis is required for the onset of anaphase. We show
      that protein dephosphorylation by protein phosphatase 1 (PP1) is also essential
      for initiating anaphase in fission yeast. PP1 may directly or indirectly regulate
      the 20S cyclosome/APC (anaphase-promoting complex) required for anaphase
      promoting proteolysis. Using anti-phosphopeptide antibodies, PP1 is shown to be
      dephosphorylated at the C-terminus, upon the onset of anaphase, for reactivation.
      sds23+, a novel gene, is a multicopy suppressor for mutations in PP1 and the 20S
      cyclosome/APC, implying that the gene dosage increase can relieve the requirement
      for PP1 and the cyclosome/APC for the onset of anaphase. The sds23+ gene is not
      essential for cell viability, but a mutant with the gene deleted cannot form
      colonies at 22 and 36 degrees C. In the sds23 deletion mutant, the progression of
      anaphase and cytokinesis is retarded and cell shape is aberrant. These defects
      are overcome by plasmids carrying the genes encoding subunits of the 20S
      cyclosome/APC or PP1. These results demonstrate functions other than promoting
      anaphase for the components of the 20S cyclosome/APC and also a close functional
      relationship of Sds23 with PP1 and 20S cyclosome/APC.

PMID- 8978690
TI  - The Schizosaccharomyces pombe rad3 checkpoint gene.
AB  - The rad3 gene of Schizosaccharomyces pombe is required for checkpoint pathways
      that respond to DNA damage and replication blocks. We report the complete rad3
      gene sequence and show that rad3 is the homologue of Saccharomyces cerevisiae
      ESR1 (MEC1/SAD3) and Drosophila melanogaster mei-41 checkpoint genes. This
      establishes Rad3/Mec1 as the only conserved protein which is required for all the
      DNA structure checkpoints in both yeast model systems. Rad3 is an inessential
      member of the 'lipid kinase' subclass of kinases which includes the ATM protein
      defective in ataxia telangiectasia patients. Mutational analysis indicates that
      the kinase domain is required for Rad3 function, and immunoprecipitation of
      overexpressed Rad3 demonstrates an associated protein kinase activity. The
      previous observation that rad3 mutations can be rescued by a truncated clone
      lacking the kinase domain may be due to intragenic complementation. Consistent
      with this, biochemical data suggest that Rad3 exists in a complex containing
      multiple copies of Rad3. We have identified a novel human gene (ATR) whose
      product is closely related to Rad3/Esr1p/Mei-41. ATR can functionally complement
      esr1-1 radiation sensitivity in S. cerevisiae. Together, the structural
      conservation and functional complementation suggest strongly that the mechanisms
      underlying the DNA structure checkpoints are conserved throughout evolution.

PMID- 8978691
TI  - Targeting presequence acquisition after mitochondrial gene transfer to the
      nucleus occurs by duplication of existing targeting signals.
AB  - We have cloned a gene for mitochondrial ribosomal protein S11 (RPS11), which is
      encoded in lower plants by the mitochondrial genome, in higher plants by the
      nuclear genome, demonstrating genetic information transfer from the mitochondrial
      genome to the nucleus during flowering plant evolution. The sequence s11-1
      encodes an N-terminal extension as well as an organelle-derived RPS11 region.
      Surprisingly, the N-terminal region has high amino acid sequence similarity with
      the presequence of the beta-subunit of ATP synthase from plant mitochondria,
      suggesting a common lineage of the presequences. The deduced N-terminal region of
      s11-2, a second nuclear-encoded homolog of rps11, shows high sequence similarity
      with the putative presequence of cytochrome oxidase subunit Vb. The sharing of
      the N-terminal region together with its 5' flanking untranslated nucleotide
      sequence in different proteins strongly suggests an involvement of
      duplication/recombination for targeting signal acquisition after gene migration.
      A remnant of ancestral rps11 sequence, transcribed and subjected to RNA editing,
      is found in the mitochondrial genome, indicating that inactivation of
      mitochondrial rps11 gene expression was initiated at the translational level
      prior to termination of transcription.

PMID- 8978692
TI  - Reconstitution of DNA base excision-repair with purified human proteins:
      interaction between DNA polymerase beta and the XRCC1 protein.
AB  - Repair of a uracil-guanine base pair in DNA has been reconstituted with the
      recombinant human proteins uracil-DNA glycosylase, apurinic/apyrimidinic
      endonuclease, DNA polymerase beta and DNA ligase III. The XRCC1 protein, which is
      known to bind DNA ligase III, is not absolutely required for the reaction but
      suppresses strand displacement by DNA polymerase beta, allowing for more
      efficient ligation after filling of a single nucleotide patch. We show that XRCC1
      interacts directly with DNA polymerase beta using far Western blotting, affinity
      precipitation and yeast two-hybrid analyses. In addition, a complex formed
      between DNA polymerase beta and a double-stranded oligonucleotide containing an
      incised abasic site was supershifted by XRCC1 in a gel retardation assay. The
      region of interaction with DNA polymerase beta is located within residues 84-183
      in the N-terminal half of the XRCC1 protein, whereas the C-terminal region of
      XRCC1 is involved in binding DNA ligase III. These data indicate that XRCC1,
      which has no known catalytic activity, might serve as a scaffold protein during
      base excision-repair. DNA strand displacement and excessive gap filling during
      DNA repair were observed in cell-free extracts of an XRCC1-deficient mutant cell
      line, in agreement with the results from the reconstituted system.

PMID- 8978693
TI  - ORC- and Cdc6-dependent complexes at active and inactive chromosomal replication
      origins in Saccharomyces cerevisiae.
AB  - We have developed a genomic footprinting protocol which allows us to examine
      protein-DNA interactions at single copy chromosomal origins of DNA replication in
      the budding yeast Saccharomyces cerevisiae. We show that active replication
      origins oscillate between two chromatin states during the cell cycle: an origin
      recognition complex (ORC)-dependent post-replicative state and a Cdc6p-dependent
      pre-replicative state. Furthermore, we show that both post- and pre-replicative
      complexes can form efficiently on closely apposed replicators. Surprisingly,
      ARS301 which is active as an origin on plasmids but not in its normal chromosomal
      location, forms ORC- and Cdc6p-dependent complexes in both its active and
      inactive contexts. Thus, although ORC and Cdc6p are essential for initiation,
      their binding is not sufficient to dictate origin use.

PMID- 8978694
TI  - The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel
      initiator element in the promoter of the human somatostatin receptor II gene.
AB  - The effects of somatostatin hormones are mediated by a family of five different
      seven-helix transmembrane spanning receptors (SSTR1-5). The expression of the
      five different SSTR subtypes displays a complex temporal- and tissue-specific
      pattern. To investigate the molecular mechanisms controlling the different
      expression patterns of the SSTRs, we cloned the 5'-flanking region of the human
      SSTR2 gene. Characterization of the SSTR2 promoter resulted in the identification
      of a novel initiator element (SSTR2inr). Transcriptional activity of the SSTR2inr
      is dependent on the presence of a binding site (E-box) for basic helix-loop-helix
      (bHLH) transcription factors. By screening a mouse brain cDNA expression library
      we isolated a cDNA coding for the bHLH transcription factor SEF-2. SEF-2 binds to
      the E-box present in the SSTR2inr, both in vitro and in vivo and activates
      transcription from the SSTR2inr. A single point mutation within the E-box
      eliminates binding of SEF-2 and results in a complete loss of transcriptional
      activity of the SSTR2inr. Furthermore, DNA binding studies demonstrate that the
      basal transcription factor TFIIB can be tethered to the SSTR2inr through physical
      interaction with SEF-2. In summary, the SSTR2inr represents a novel type of
      initiator element that confers gene expression in the absence of a TATA-box or
      binding sites for other known initiator factors, like YY-1 or USF.

PMID- 8978695
TI  - A T cell controlled molecular pathway regulating the IgH locus: CD40-mediated
      activation of the IgH 3' enhancer.
AB  - Immunoglobulin heavy chain (IgH) class switch recombination and regulation of IgH
      expression levels are processes suggested to be controlled by the IgH 3'
      enhancer. Here we demonstrate that CD40 or IgM receptor stimulation of primary B
      cells results in transactivation of this enhancer. 4-Hydroxy-3-nitrophenylacetyl
      (NIP)-BSA induction of a K46 B cell line expressing a chimeric NIP-specific CD40
      single chain receptor results in a ligand receptor-dependent response of a 3'
      enhancer ETS/AP-1 minimal promoter construct. Gel retardation analysis and
      genomic footprinting experiments reveal that CD40 or IgM induction recruits NFAB
      (nuclear factors of activated B cells) to the ETS/AP-1 motif. While IgM
      signalling recruits c-Fos, JunB and Elf-1 (NFAB-I), only JunB and Elf-1 were
      observed following CD40 signalling (NFAB-II). CD40 signalling, however, induces a
      Fos family-related partner for JunB, which may account for the transcriptional
      activity observed by NFAB-II in K46 cells. We propose a model whereby CD40 and
      IgM receptor-mediated signalling converge in the process of 3' enhancer
      activation in B lymphocytes. Our data provide a putative molecular explanation as
      to why CD40L-deficient mice, and possibly patients with hyper-IgM syndrome, are
      unable to undergo T cell-dependent class switch recombination but respond
      properly upon lipopolysaccharide-induced switch recombination.

PMID- 8978696
TI  - A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of
      transcription by nuclear receptors.
AB  - Nuclear receptors (NRs) are ligand-inducible transcription factors that mediate
      complex effects on development, differentiation and homeostasis. They regulate
      the transcription of their target genes through binding to cognate DNA sequences
      as homodimers or heterodimers. The molecular mechanisms underlying
      transcriptional activation by NRs are still poorly understood, although
      intermediary factors (mediators) appear to be involved in mediating the
      transactivation functions of NRs. TIF1 has been identified previously as a
      protein that interacts specifically with the ligand binding domain of several
      nuclear receptors, both in yeast and in vitro. The characteristics of these
      interactions have led us to suggest that TIF1 might be a mediator of the NR
      ligand-inducible activation function AF-2. Using a two-hybrid screening in yeast,
      we have now identified two TIF1-binding proteins, mHP1 alpha and mMOD1, that are
      mouse homologues of the Drosophila heterochromatinic protein 1. Using mHP1 alpha
      as a bait in a second two-hybrid screening, we have isolated cDNAs encoding
      proteins that are also very likely to be involved in chromatin structure and
      function, as well as a protein structurally and functionally related to TIF1
      (renamed TIF1 alpha), which was named TIF1 beta. Here we discuss how the function
      of members of the TIF1 family in the control of transcription could be exerted at
      the level of the structure of the chromatin template.

PMID- 8978697
TI  - Different mechanisms control signal-induced degradation and basal turnover of the
      NF-kappaB inhibitor IkappaB alpha in vivo.
AB  - The transcription factor NF-kappaB is sequestered in the cytoplasm by a family of
      IkappaB molecules. Upon cellular stimulation with diverse agents, one of these
      molecules, IkappaB alpha, is rapidly phosphorylated and subsequently degraded.
      This process triggers nuclear translocation of NF-kappaB and the successive
      activation of target genes. Independent of its rapid stimulation-induced
      breakdown, IkappaB alpha is inherently unstable and undergoes a continuous
      turnover. To compare the mechanisms and protein domains involved in inducible and
      basal degradation of IkappaB alpha in intact cells we employed a transfection
      strategy using tagged IkappaB alpha and ubiquitin molecules. We show that tumor
      necrosis factor alpha (TNFalpha) induced breakdown of IkappaB alpha but not its
      basal turnover coincides with ubiquitination in the amino-terminal signal
      response domain (SRD) of IkappaB alpha. Neither the SRD nor the carboxy-terminal
      PEST sequence is needed for basal turnover, which instead depends only on the
      core ankyrin repeat domain. Despite the differences in the requirements of
      protein domains and ubiquitin-conjugation for both degradation pathways, each one
      is mediated by the proteasome. This finding is important for understanding
      alternative modes of controlling NF-kappaB activity.

PMID- 8978698
TI  - Function of the Evx-2 gene in the morphogenesis of vertebrate limbs.
AB  - Vertebrate gene members of the HoxD complex are essential for proper development
      of the appendicular skeletons. Inactivation of these genes induces severe
      alterations in the size and number of bony elements. Evx-2, a gene related to the
      Drosophila even-skipped (eve) gene, is located close to Hoxd-13 and is expressed
      in limbs like the neighbouring Hoxd genes. To investigate whether this tight
      linkage reflects a functional similarity, we produced a null allele of Evx-2.
      Furthermore, and because Hoxd-13 function is prevalent over that of nearby Hoxd
      genes, we generated two different double mutant loci wherein both Evx-2 and Hoxd
      13 were inactivated in cis. The analysis of these various genetic configurations
      revealed the important function of Evx-2 during the development of the autopod as
      well as its genetic interaction with Hoxd-13. These results show that, in limbs,
      Evx-2 functions like a Hoxd gene. A potential evolutionary scenario is discussed,
      in which Evx-2 was recruited by the HoxD complex in conjunction with the
      emergence of digits in an ancestral tetrapod.

PMID- 8978699
TI  - Antagonistic actions of activin A and BMP-2/4 control dorsal lip-specific
      activation of the early response gene XFD-1' in Xenopus laevis embryos.
AB  - Transcription of the early response gene XFD-1' (XFKH1) in the dorsal lip
      (Spemann organizer) of Xenopus embryos is activated by dorsal mesoderm inducing
      factors. Promoter studies revealed the presence of an activin A response element
      (ARE) which is both necessary and sufficient for transcriptional activation of
      reporter genes in animal cap explants incubated with activin A. Surprisingly,
      this ARE is also active within vegetal explants in the absence of exogenously
      added inducers, but an additional inhibitory response element prevents
      transcription of the XFD-1' gene in the ventral/vegetal region of the embryo in
      vivo. This element is located upstream of the ARE, it responds to bone
      morphogenic proteins 2 and 4 (BMP-2/4) triggered signals and it overrides the
      activating properties of the ARE. Expression patterns of BMP-2 and BMP-4 in the
      late blastula stage embryo and, especially, their absence from the dorsal
      blastopore lip may thus control the spatial transcription of the XFD-1' gene.
      Accordingly, the temporal activation and the spatial restriction of XFD-1' gene
      activity to the Spemann organizer is regulated by antagonistic actions of two
      distinct members of the TGF-beta family (activin and BMP) which act on different
      promoter elements.

PMID- 8978701
TI  - Guide RNA-directed uridine insertion RNA editing in vitro.
AB  - Guide RNAs (gRNAs) have been proposed to mediate uridine (U) addition/deletion
      editing of mitochondrial mRNAs in kinetoplastid protozoa. The Us are proposed to
      be derived either from UTP by two successive cleavage-ligations or
      transesterifications, or from the 3' end of the gRNA by the same mechanisms. We
      have demonstrated gRNA-dependent U insertions into a specific editing site of a
      pre-edited mRNA which was incubated in a mitochondrial extract from Leishmania
      tarentolae. The predominant number of U insertions was determined by the number
      of guiding nucleotides in the added gRNA, and the formation of a gRNA-mRNA anchor
      duplex was necessary for activity. UTP and alpha-beta bond hydrolysis of ATP were
      required, and the activity was inhibited above 50-100 mM KCl. A gRNA-independent
      insertion of up to approximately 13 Us occurred in the absence of the added
      cognate gRNA; the extent of this activity was affected by sequences upstream and
      downstream of the edited region. Heparin inhibited the gRNA-independent U
      insertion activity and had no effect on the gRNA-dependent activity. Blocking the
      3' OH of the gRNA had little effect on the gRNA-dependent U insertion activity.
      The data are consistent with a cleavage-ligation model in which the Us are
      derived directly from UTP.

PMID- 8978700
TI  - Heat shock disassembles the nucleolus and inhibits nuclear protein import and
      poly(A)+ RNA export.
AB  - Heat shock causes major positive and negative changes in gene expression,
      drastically alters the appearance of the nucleolus and inhibits rRNA synthesis.
      We here show that it causes many yeast nucleolar proteins, including the
      fibrillarin homolog Nop1p, to relocate to the cytoplasm. Relocation depends on
      several proteins implicated in mRNA transport (Mtrps) and is reversible. Two
      observations indicate, surprisingly, that disassembly results from a reduction in
      Ssa protein (Hsp70) levels: (i) selective depletion of Ssa1p leads to disassembly
      of the nucleolus; (ii) preincubation at 37 degrees C protects the nucleolus
      against disassembly by heat shock, unless expression of Ssa proteins is
      specifically inhibited. We observed that heat shock or reduction of Ssa1p levels
      inhibits protein import into the nucleus and therefore we propose that inhibition
      of import leads to disassembly of the nucleolus. These observations provide a
      simple explanation of the effects of heat shock on the anatomy of the nucleolus
      and rRNA transcription. They also extend understanding of the path of nuclear
      export. Since a number of nucleoplasmic proteins also relocate upon heat shock,
      these observations can provide a general mechanism for regulation of gene
      expression. Relocation of the hnRNP-like protein Mtr13p (= Npl3p, Nop3p),
      explains the heat shock sensitivity of export of average poly(A)+ RNA.
      Strikingly, Hsp mRNA export appears not to be affected.

PMID- 8978702
TI  - The G222D mutation in elongation factor Tu inhibits the codon-induced
      conformational changes leading to GTPase activation on the ribosome.
AB  - Elongation factor Tu (EF-Tu) from Escherichia coli carrying the mutation G222D is
      unable to hydrolyze GTP on the ribosome and to sustain polypeptide synthesis at
      near physiological Mg2+ concentration, although the interactions with guanine
      nucleotides and aminoacyl-tRNA are not changed significantly. GTPase and
      polypeptide synthesis activities are restored by increasing the Mg2+
      concentration. Here we report a pre-steady-state kinetic study of the binding of
      the ternary complexes of wild-type and mutant EF-Tu with Phe-tRNA(Phe) and GTP to
      the A site of poly(U)-programed ribosomes. The kinetic parameters of initial
      binding to the ribosome and subsequent codon-anticodon interaction are similar
      for mutant and wild-type EF-Tu, independent of the Mg2+ concentration, suggesting
      that the initial interaction with the ribosome is not affected by the mutation.
      Codon recognition following initial binding is also not affected by the mutation.
      The main effect of the G222D mutation is the inhibition, at low Mg2+
      concentration, of codon-induced structural transitions of the tRNA and, in
      particular, their transmission to EF-Tu that precedes GTP hydrolysis and the
      subsequent steps of A-site binding. Increasing the Mg2+ concentration to 10 mM
      restores the complete reaction sequence of A-site binding at close to wild-type
      rates. The inhibition of the structural transitions is probably due to the
      interference of the negative charge introduced by the mutation with negative
      charges either of the 3' terminus of the tRNA, bound in the vicinity of the
      mutated amino acid in domain 2 of EF-Tu, or of the ribosome. Increasing the Mg2+
      concentration appears to overcome the inhibition by screening the negative
      charges.

PMID- 8978703
TI  - Two intracellular signaling pathways for the dopamine D3 receptor: opposite and
      synergistic interactions with cyclic AMP.
AB  - As cerebral neurons express the dopamine D1 receptor positively coupled with
      adenylyl cyclase, together with the D3 receptor, we have investigated in a
      heterologous cell expression system the relationships of cyclic AMP with D3
      receptor signaling pathways. In NG108-15 cells transfected with the human D3
      receptor cDNA, dopamine, quinpirole, and other dopamine receptor agonists
      inhibited cyclic AMP accumulation induced by forskolin. Quinpirole also increased
      mitogenesis, assessed by measuring [3H]thymidine incorporation. This effect was
      blocked partially by genistein, a tyrosine kinase inhibitor. Forskolin enhanced
      by 50-75% the quinpirole-induced [3H]thymidine incorporation. This effect was
      maximal with 100 nM forskolin, occurred after 6-16 h, was reproduced by cyclic
      AMP-permeable analogues, and was blocked by a protein kinase A inhibitor.
      Forskolin increased D3 receptor expression up to 135%, but only after 16 h and at
      concentrations of > 1 microM. Thus, in this cell line, the D3 receptor uses two
      distinct signaling pathways: it efficiently inhibits adenylyl cyclase and induces
      mitogenesis, an effect possibly involving tyrosine phosphorylation. Activation of
      the cyclic AMP cascade potentiates the D3 receptor-mediated mitogenic response,
      through phosphorylation by a cyclic AMP-dependent kinase of a yet unidentified
      component. Hence, transduction of the D3 receptor can involve both opposite and
      synergistic interactions with cyclic AMP.

PMID- 8978705
TI  - Retinoic acid is a negative regulator of the neuropeptide Y/peptide YY Y1
      receptor gene in SK-N-MC cells.
AB  - To identify effectors of neuropeptide Y Y1 receptor gene expression predicted by
      putative regulatory elements in its 5' flanking region, we examined the effects
      of several transcriptionally active agents on Y1 receptor mRNA levels and 125I
      peptide YY binding capacity in SK-N-MC cells. Phorbol ester caused a rapid,
      transient 2.6-fold increase in Y1R mRNA levels. However, all trans-retinoic acid
      caused a rapid, sustained decrease in Y1 receptor mRNA levels (to 25% of
      control). Cycloheximide pretreatment did not attenuate the maximal inhibitory
      effect of retinoic acid, but it prolonged the time to achieve maximal efficacy.
      The retinoic acid effect was secondary to both a significant decrease in Y1
      receptor mRNA stability and a decreased Y1 receptor gene transcription rate. Y1
      receptor binding capacity was also significantly decreased after retinoic acid
      treatment (368 +/- 25 vs. 496 +/- 28 fmol/mg of protein for control). These data
      support a role for retinoic acid as an important agent regulating Y1 receptor
      gene expression and mediating Y1 receptor down-regulation.

PMID- 8978704
TI  - Insulin promotes the hydrolysis of a glycosyl phosphatidylinositol in cultured
      rat astroglial cells.
AB  - Glycosyl phosphatidylinositols have been implicated in insulin signaling through
      their action as precursors of second messenger molecules in peripheral tissues.
      In the present study, cultured rat astrocytes were used to investigate whether
      glycosyl phosphatidylinositol might be involved in the mechanism of insulin
      signal transduction in neural cells. A glycosyl phosphatidylinositol sensitive to
      hydrolysis by both phosphatidylinositol-specific phospholipase C and glycosyl
      phosphatidylinositol-specific phospholipase D and to nitrous acid deamination was
      purified. When astrocytes were exposed to 10 nM insulin, a rapid and significant
      reduction in the content of glycosyl phosphatidylinositol was observed within 1-2
      min. In addition, an inverse concentration-dependent relationship between
      glycosyl phosphatidylinositol and diacylglycerol levels was found, suggesting a
      phospholipase C-mediated hydrolysis of glycosyl phosphatidylinositol in response
      to insulin. The effects of insulin were mediated through its own receptors and
      not through insulin-like growth factor (IGF)-I and/or IGF-II receptors, as
      demonstrated by affinity cross-linking studies. Also, the effects of 5 nM IGF-1
      or 5 nM IGF-II on glycosyl phosphatidylinositol and diacylglycerol levels were
      different from those caused by insulin and were not essentially modified by
      pretreatment of the cells with either platelet-derived growth factor (PDGF) or
      epidermal growth factor (EGF). When cells were sequentially incubated with PDGF
      and EGF, a reduction in both glycosyl phosphatidylinositol and diacylglycerol
      contents was observed; the diacylglycerol but not the glycosyl phosphatidyl
      content was reversed after incubation with IGF-I, and especially with IGF-II, for
      10 min. Despite the remarkable homology among insulin, IGF-I, and IGF-II, our
      results indicate that in astrocytes these compounds probably use different signal
      transduction pathways.

PMID- 8978706
TI  - Pigment epithelium-derived factor protects cultured cerebellar granule cells
      against glutamate-induced neurotoxicity.
AB  - Pigment epithelium-derived factor (PEDF) is a survival factor for cerebellar
      granule cells in culture. In the present study, we have investigated the ability
      of a recombinant form of PEDF (rPEDF) to protect against glutamate neurotoxicity.
      When rPEDF was added to cerebellar granule cell cultures 30 min before addition
      of 100 microM glutamate, glutamate-induced neuronal death was significantly
      reduced. The protective effect of rPEDF was dose-dependent in the range from
      0.023 to 7.0 nM (1-500 ng/ml), with a half-maximal dose of 0.47 nM. An antibody
      to rPEDF blocked this protective effect. Measurement of intraneuronal free
      calcium levels demonstrated that rPEDF raised the basal calcium content. However,
      after the elevation of intracellular calcium in response to administration of
      glutamate, rPEDF reduced the plateau level seen in the presence of glutamate.
      These data show that PEDF can protect neurons against glutamate-induced
      neurotoxicity, possibly via a calcium-related pathway. The finding that only 30
      min of preincubation is required for the neuroprotective effect, significantly
      faster than other known neurotrophic factors, suggests that PEDF may be useful
      clinically as a neuroprotective agent in the CNS.

PMID- 8978707
TI  - L-deprenyl protects mesencephalic dopamine neurons from glutamate receptor
      mediated toxicity in vitro.
AB  - L-Deprenyl is a relatively selective inhibitor of monoamine oxidase (MAO)-B that
      delays the emergence of disability and the progression of signs and symptoms of
      Parkinson's disease. Experimentally, deprenyl has also been shown to prevent
      neuronal cell death in various models through a mechanism that is independent of
      MAO-B inhibition. We examined the effect of deprenyl on cultured mesencephalic
      dopamine neurons subjected to daily changes of feeding medium, an experimental
      paradigm that causes neuronal death associated with activation of the NMDA
      subtype of glutamate receptors. Both deprenyl (0.5-50 microM) and the NMDA
      receptor blocker MK-801 (10 microM) protected dopamine neurons from damage caused
      by medium changes. The nonselective MAO inhibitor pargyline (0.5-50 microM) was
      not protective, indicating that protection by deprenyl was not due to MAO
      inhibition. Deprenyl (50 microM) also protected dopamine neurons from delayed
      neurotoxicity caused by exposure to NMDA. Because deprenyl had no inhibitory
      effect on NMDA receptor binding, it is likely that deprenyl protects from events
      occurring downstream from activation of glutamate receptors. As excitotoxic
      injury has been implicated in neurodegeneration, it is possible that deprenyl
      exerts its beneficial effects in Parkinson's disease by suppressing excitotoxic
      damage.

PMID- 8978708
TI  - Effect of continuous phorbol ester treatment on muscarinic receptor-mediated
      calmodulin redistribution in SK-N-SH neuroblastoma cells.
AB  - Stimulation of muscarinic receptors by carbachol and activation of protein kinase
      C elicits the translocation of calmodulin (CaM) from membranes to cytosol in the
      human neuroblastoma cell line SK-N-SH. Our previous studies have suggested a role
      for protein kinase C in the regulation of CaM redistribution. To explore further
      the role of protein kinase C in carbachol-induced calmodulin translocation, we
      treated cells for 17 h with 12-O-tetradecanoylphorbol 13-acetate (TPA) to down
      regulate protein kinase C isozymes or 72 h to differentiate the cells. Treatment
      of SK-N-SH cells for 17 h with 70 nM TPA nearly abolished the effect of carbachol
      on CaM redistribution. After 72 h of TPA, however, the cells appeared
      differentiated, and the ability of carbachol to increase cytosolic CaM levels was
      restored. In untreated control cells, the carbachol-mediated increase in
      cytosolic CaM content was mimicked by TPA and blocked by pretreatment with the
      selective protein kinase C inhibitor Ro 31-8220 at 10 microM. In the 72-h TPA
      treated cells, however, the ability of TPA to increase cytosolic CaM levels was
      significantly reduced, and the action of carbachol was no longer blocked by Ro 31
      8220. The effect of prolonged TPA treatment on select protein kinase C isozymes
      was examined by immunoblotting. Treatment of cells for either 17 or 72 h
      abolished the alpha-isozyme in the cytosol and reduced (17 h) or abolished (72 h)
      the content in the membranes. In both 17- and 72-h TPA-treated cells, the epsilon
      isozyme was nearly abolished in the cytosol and slightly reduced in the
      membranes. Some protein kinase C activity may have been maintained during TPA
      treatment because the basal level of phosphorylation of the protein kinase C
      substrate myristoylated alanine-rich C kinase substrate was enhanced in cells
      treated for either 17 or 72 h with TPA. The potential dissociation of carbachol
      and protein kinase C in eliciting increases in cytosolic CaM content was a
      function of prolonged TPA treatment and not differentiation per se because
      carbachol-mediated increases in cytosolic CaM levels were inhibited by Ro 31-8220
      in retinoic acid-differentiated SK-N-SH cells. This study demonstrates that
      continuous TPA treatment, although initially down-regulating the protein kinase C
      mediated effect of carbachol on CaM redistribution, uncouples carbachol and
      protein kinase C at longer times.

PMID- 8978709
TI  - Regulation of alpha 2A-adrenergic receptor mRNA in rat astroglial cultures: role
      of cyclic AMP and protein kinase C.
AB  - In this study we investigated regulation of alpha 2A-adrenergic receptor (alpha
      2A-AR) mRNA in rat astroglial cultures by increases in intracellular cyclic AMP
      levels and by protein kinase C (PKC) activation. Treatment of astroglial cultures
      with forskolin (FSK), an adenylyl cyclase activator, or with the membrane
      permeable cyclic AMP analogues dibutyryl cyclic AMP or Sp-adenosine 3',5'-cyclic
      monophosphothioate triethylamine caused time- and concentration-dependent
      decreases in the levels of a approximately 4.0-kb alpha 2A-AR mRNA transcript.
      Levels of alpha 2A-AR mRNA were reduced to approximately 10% of control levels
      within 4 h of 1 microM FSK treatment. PKC agonists [phorbol 12-myristate 13
      acetate (PMA), phorbol 12,13-dibutyrate, and mezerein] also decreased alpha 2A-AR
      mRNA levels in a time- and concentration-dependent fashion. A 90% decrease in
      alpha 2A-AR mRNA levels was observed with 50 nM PMA in 4 h. The decrease in alpha
      2A-AR mRNA levels caused by FSK and PMA treatment appears to be the result of
      decreases in transcription of the alpha 2A-AR gene and is not due to decreases in
      alpha 2A-AR mRNA degradation rate. These observations suggest that alpha 2A-AR
      mRNA levels are regulated by cyclic AMP and PKC.

PMID- 8978710
TI  - Transgenic murine dopaminergic neurons expressing human Cu/Zn superoxide
      dismutase exhibit increased density in culture, but no resistance to
      methylphenylpyridinium-induced degeneration.
AB  - Primary dopaminergic neuronal cultures with increased superoxide dismutase (SOD)
      activity were established for studying the role of superoxide anion (O2-) in 1
      methyl-4-phenylpyridinium (MPP+)-induced degeneration of dopamine (DA) neurons.
      Mean SOD activity in cultures prepared from transgenic (human) Cu/Zn SOD (hSOD1)
      mice was 2.46-2.60 times greater than in cultures prepared from nontransgenic
      control mice. After 1 and 2 weeks in culture, the mean density of DA neurons
      [number of tyrosine hydroxylase-immunoreactive (TH-ir) cells per visual field]
      was significantly higher in cultures prepared from transgenic mice compared with
      those prepared from nontransgenic control mice (4.55-5.63 TH-ir neurons per field
      in hSOD1 cultures vs. 2.66-2.8 TH-ir neurons per field in control cultures).
      However, uptake of [3H]DA relative to uptake of [3H]GABA was only slightly
      greater in hSOD1 cultures than in normal cultures (14.1 nmol of DA/100 nmol of
      GABA vs. 12.1 nmol of DA/100 nmol of GABA). Resistance to MPP+ toxicity was not
      significantly different from that in normal cultures when based on density of
      surviving TH-ir cell bodies (EC50 = 0.54 microM in hSOD1 and EC50 = 0.37 microM
      in normal cultures). A more sensitive measure of DA neuron integrity and function
      ([3H]DA uptake) also failed to demonstrate increased resistance of hSOD1 cultures
      to the toxin (EC50 = 73.7 nM in hSOD1 and EC50 = 86.2 nM in controls). These
      results do not support the hypothesis that neurotoxicity of the active metabolite
      of MPTP, MPP+, is mediated by generation of O2- in the cytoplasm. Nevertheless,
      mesencephalic cultures with increased hSOD1 activity appear to survive better
      than normal control cultures in the oxidatively stressful environment of cell
      culture incubators, and such mesencephalic cells may be useful for cell grafting
      studies in animal models of Parkinson's disease.

PMID- 8978711
TI  - Neurotrophin protection against toxicity induced by low potassium and
      nitroprusside in cultured cerebellar granule neurons.
AB  - Long-term survival of cultured rat cerebellar granule neurons requires
      depolarizing concentrations of potassium (high potassium; 25 mM KCl). A high
      potassium culturing condition has been reported to increase the intracellular
      calcium concentration ([Ca2+]i) and the expression of brain-derived neurotrophic
      factor (BDNF), which in turn induces the expression of neurotrophin-3 (NT-3) in
      these neurons. We therefore examined the neurotrophic effect of these two
      neurotrophins in low-potassium (5 mM) cultures and their neuroprotective
      capabilities against sodium nitroprusside-induced neurotoxicity in both low- and
      high-potassium cultures. Neuronal survival and neurotrophic effects were
      monitored by [3H]ouabain binding and 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assays. In low-potassium cultures, the neurotrophic
      effect of BDNF approached that found in high-potassium cultures but was much more
      robust than that of NT-3. In contrast, undifferentiated neurons cultured in high
      potassium medium were much less responsive to BDNF and not responsive at all to
      NT-3. Induction of nitroprusside neurotoxicity occurred more readily in low- than
      in high-potassium cultures. BDNF, NT-3, and a high potassium concentration, alone
      or in combination, were unable to protect neurons treated with nitroprusside at
      50 or 100 microM. However, the neurotoxicity of a lower dose of nitroprusside (10
      microM) was reversed by the combined actions of these two neurotrophins in low
      potassium cultures and by BDNF alone in high-potassium cultures. Because
      nitroprusside neurotoxicity is less robust in high-potassium cultures, high
      potassium-induced BDNF expression and subsequent NT-3 expression may participate
      in its neuroprotection and neurotrophism in these cultures. Also, we found that
      toxic doses of nitroprusside antagonized KCl- and NMDA-induced rises in [Ca2+]i,
      suggesting that this effect is related to nitroprusside-induced neurotoxicity.

PMID- 8978712
TI  - Endothelin stimulates phospholipase D in striatal astrocytes.
AB  - In primary cultures of mouse striatal astrocytes prelabeled with [3H]myristic
      acid, endothelin (ET)-1 induced a time-dependent formation of [3H]phosphatidic
      acid and [3H]diacylglycerol. In the presence of ethanol, a production of
      [3H]phosphatidylethanol was observed, indicating the activation of a
      phospholipase D (PLD). ET-1 and ET-3 were equipotent in stimulating PLD activity
      (EC50 = 2-5 nM). Pretreatment of the cells with pertussis toxin partially
      abolished the effect of ET-1, indicating the involvement of a Gi/G(o) protein.
      Inhibition of protein kinase C by Ro 31-8220 or down-regulation of the kinase by
      a long-time treatment with phorbol 12-myristate 13-acetate (PMA) totally
      abolished the ET-1-induced stimulation of PLD. In contrast, a cyclic AMP
      dependent process is not involved in the activation of PLD, because the ET-1
      evoked formation of [3H]phosphatidylethanol was not affected when cells were
      coincubated with either isoproterenol, 8-bromo-cyclic AMP, or forskolin. Acute
      treatment with PMA also stimulated PLD through a protein kinase C-dependent
      process. However, the ET-1 and PMA responses were additive. Furthermore, the ET-1
      evoked response, contrary to that of PMA, totally dependent on the presence of
      extracellular calcium. These results suggest that at least two distinct
      mechanisms are involved in the control of PLD activity in striatal astrocytes.
      Finally, ET-1, ET-3, and PMA also stimulated PLD in astrocytes from the
      mesencephalon, the cerebral cortex, and the hippocampus.

PMID- 8978713
TI  - K-252b potentiation of neurotrophin-3 is trkA specific in cells lacking p75NTR.
AB  - K-252b potentiates the neurotrophic effects of neurotrophin-3 (NT-3) in primary
      cultures of rat central cholinergic and peripheral sensory neurons and in a rat
      pheochromocytoma PC12 cell line. The ligand and receptor specificity, and role of
      the low-affinity neurotrophin receptor (p75NTR) in the potentiation response
      induced by K-252b, are unknown. To address the issues of ligand and receptor
      specificity of K-252b potentiation, we have examined neurotrophin-induced DNA
      synthesis ([3H]-thymidine incorporation) in NIH3T3 cells expressing trkA, trkB,
      or trkC. Neither NT-3 nor K-252b alone could stimulate mitogenic activity in the
      trkA-overexpressing clone. However, coaddition of K-252b (EC50 of approximately 2
      nM) with 10-100 ng/ml NT-3 led to incorporation of [3H]thymidine in trkA
      expressing cells to a level induced by optimal concentrations of nerve growth
      factor (NGF). The K-252b- and NT-3-induced [3H]thymidine incorporation correlated
      with an increase in the tyrosine autophosphorylation of the trkA receptor as well
      as tyrosine phosphorylation of trk-associated phospholipase C-gamma 1 and SH2
      containing proteins. K-252b did not potentiate submaximal doses of NGF, or
      maximal doses of brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5 (NT
      4/ 5) in trkA-expressing cells. Furthermore, K-252b did not potentiate DNA
      synthesis by submaximal doses of BDNF, NT-4/5, or NT-3 in trkB- or trkC
      expressing NIH3T3 cells, suggesting that the potentiation profile for K-252b was
      specific for NT-3 in trkA-expressing cells. We found no expression of p75NTR in
      the trk-expressing NIH3T3 cells. This is the first demonstration that K-252b
      potentiates a trkA-mediated biological nonneuronal response by NT-3 that occurs
      independent of p75NTR and appears to be both ligand and receptor specific.

PMID- 8978714
TI  - Nitric oxide disrupts Ca2+ homeostasis in hippocampal neurons.
AB  - Nitric oxide has been recognized in recent years as an important mediator of
      neuronal toxicity, which in many cases involves alterations of the cytoplasmic
      Ca2+ concentration ([Ca2+]i). In [Ca2+]i fluorimetric experiments on cultured
      hippocampal neurons, the nitric oxide-releasing agent S-nitrosocysteine produced
      a delayed rise in [Ca2+]i over a 20-min exposure, which was accompanied by a
      progressive slowing of the kinetics of recovery from depolarization-induced
      [Ca2+]i transients. These effects were blocked by oxyhemoglobin and by superoxide
      dismutase, confirming nitric oxide as the responsible agent, and suggesting that
      they involved peroxynitrite formation. Similar alterations of [Ca2+]i homeostasis
      were produced by the mitochondrial ATP synthase inhibitor oligomycin, and when an
      ATP-regenerating system was supplied via the patch pipette in combined whole-cell
      patch-clamp-[Ca2+]i fluorimetry experiments, S-nitrosocysteine had no effect on
      the resting [Ca2+]i or on the recovery kinetics of [Ca2+]i transients induced by
      direct depolarization. We conclude that prolonged exposure to nitric oxide
      disrupts [Ca2+]i homeostasis in hippocampal neurons by impairing Ca2+ removal
      from the cytoplasm, possibly as a result of ATP depletion. The resulting
      persistent alterations in [Ca2+]i may contribute to the delayed neurotoxicity of
      nitric oxide.

PMID- 8978715
TI  - Okadaic acid induces hyperphosphorylation of tau independently of mitogen
      activated protein kinase activation.
AB  - Hyperphosphorylation of the microtubule-associated protein tau is a
      characteristic of Alzheimer brain tissue. Recent in vitro data suggest that
      mitogen-activated protein kinase (MAPK), a proline-directed protein kinase,
      phosphorylates the sites on tau common to Alzheimer's disease. Using an okadaic
      acid-induced tau hyperphosphorylation model, we have tested the requirement for
      MAPK activity, using a specific inhibitor ?PD098059 [2-(2'-amino-3'
      methoxyphenyl)oxanaphthalen-4-one]? of the MAPK activator Mek1. Mobility shift,
      phosphoepitope analysis, and direct measurement of kinase activity indicated that
      the Mek1 inhibitor dose-dependently blocked basal and okadaic acid-induced MAPK
      activation. Despite a block of MAPK activation by this inhibitor, robust tau
      hyperphosphorylation was observed in response to okadaic acid. In addition,
      activation of MAPK by phorbol 12-myristate 13-acetate did not result in tau
      phosphorylation, indicating that in primary cultures of cortical neurons elevated
      MAPK activity is not sufficient to induce tau hyperphosphorylation.

PMID- 8978716
TI  - Glial regulation of alpha 7-type nicotinic acetylcholine receptor expression in
      cultured rat cortical neurons.
AB  - Primary embryonic cortical cultures were used as an in vitro model to evaluate
      the influence of glia on developmental expression of alpha 7-type nicotinic
      acetylcholine receptors in rat brain. In cells cultured in serum-containing
      medium without mitotic inhibitors, specific 125I-alpha-bungarotoxin binding to
      alpha 7-type nicotinic receptors was maximal 4-8 days after plating. Treatment
      with 5'-fluorodeoxyuridine (80 microM) from 1 to 3 days in vitro significantly
      reduced glial proliferation and concomitantly increased 125I-alpha-bungarotoxin
      binding, whereas plating onto a glial bed layer decreased binding. There was no
      significant binding to pure glial cultures. Treatment-induced changes in neuronal
      binding resulted from alterations in receptor density, with no change in
      affinity. 5'-Fluorodeoxyuridine treatment also increased cellular expression of
      alpha 7 receptor mRNA but had no effect on N-[3H]methylscopolamine binding to
      muscarinic receptors. Glial conditioned medium decreased 125I-alpha-bungarotoxin
      binding in both control and 5'-fluorodeoxyuridine-treated cultures, suggesting
      the release of a soluble factor that inhibits alpha 7-type nicotinic receptor
      expression. An additional mechanism of glial regulation may involve removal of
      glutamate from the surrounding medium, as added glutamate (200 microM) increased
      125I-alpha-bungarotoxin binding in astrocyte-poor cultures but not in those that
      were astrocyte enriched. These results suggest that glia may serve a
      physiological role in regulating alpha 7-type nicotinic receptors in developing
      brain.

PMID- 8978717
TI  - Chronic ethanol administration regulates the expression of GABAA receptor alpha 1
      and alpha 5 subunits in the ventral tegmental area and hippocampus.
AB  - Ethanol dependence and tolerance involve perturbation of GABAergic
      neurotransmission. Previous studies have demonstrated that ethanol treatment
      regulates the function and expression of GABAA receptors throughout the CNS.
      Conceivably, changes in receptor function may be associated with alterations of
      subunit composition. In the present study, a comprehensive (1-12 weeks) ethanol
      treatment paradigm was used to evaluate changes in GABAA receptor subunit
      expression in several brain regions including the cerebellum, cerebral cortex,
      ventral tegmental area (VTA) (a region implicated in drug reward/dependence), and
      the hippocampus (a region involved in memory/cognition). Expression of alpha 1
      and alpha 5 subunits was regulated by ethanol in a region-specific and time
      dependent manner. Following 2-4 weeks of administration, cortical and cerebellar
      alpha 1 and alpha 5 subunits immunoreactivity was reduced. In the VTA, levels of
      alpha 1 subunit immunoreactivity were significantly decreased after 12 weeks but
      not 1-4 weeks of treatment. Hippocampal alpha 1 subunit immunoreactivity and mRNA
      content were also significantly reduced after 12 but not after 4 weeks of
      treatment. In contrast, alpha 5 mRNA content was increased in this brain region.
      These data indicate that chronic ethanol administration alters GABAA receptor
      subunit expression in the VTA and hippocampus, effects that may play a role in
      the abuse potential and detrimental cognitive effects of alcohol.

PMID- 8978718
TI  - 5-Hydroxytryptamine-facilitated release of substance P from rat spinal cord
      slices is mediated by nitric oxide and cyclic GMP.
AB  - The role of nitric oxide (NO) in the control of 5-hydroxytryptamine (5-HT)
      induced release of substance P was investigated in rat spinal cord in vitro. 5-HT
      facilitated the 60 mM K(+)-evoked release of substance P-like immunoreactive
      materials (SPLI) from the superfused rat dorsal spinal cord slices without
      affecting spontaneous SPLI release. The facilitatory effect of 5-HT was
      significantly inhibited by ICS 205-930 or granisetron (potent and specific 5-HT3
      receptor antagonists), by NG-monomethyl-L-arginine (NMMA, a NO synthase
      inhibitor), and by methylene blue or 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1
      one (MB or ODQ, respectively; both are inhibitors of soluble guanylyl cyclase)
      and was mimicked by 2-methylserotonin (2-m-5-HT, a selective 5-HT3 receptor
      agonist), L-arginine (a precursor of NO), or 8-bromo-cyclic GMP. NMMA, MB, or ODQ
      inhibited the 2-m-5-HT-induced increase of cyclic GMP levels in the rat dorsal
      spinal cord slices. These data suggest that the facilitatory effect of 5-HT on
      the release of SPLI is mediated by the 5-HT3 receptor and that the intracellular
      signaling is mediated via NO by an increase in cyclic GMP production.

PMID- 8978719
TI  - Down-regulation of norepinephrine transporters on PC12 cells by transporter
      inhibitors.
AB  - To investigate the regulation of norepinephrine transporters (NETs) in vitro, we
      measured the binding of the NET-selective ligand [3H]nisoxetine in homogenates of
      PC12 cells after exposure of intact cells to the NET inhibitor desipramine (DMI).
      A 3-day exposure of PC12 cells to DMI robustly reduced the Bmax, but not the KD,
      of [3H]nisoxetine binding to NETs. Reduction of the binding of [3H]nisoxetine was
      dependent on both the concentration of DMI and the time of exposure to DMI.
      Reduction of [3H]nisoxetine binding to NETs produced by a 1-day exposure to DMI
      reverted to preexposure levels 48 h after cessation of DMI exposure. Similar down
      regulation of NETs was found when PC12 cells were exposed to another NET
      selective drug, nisoxetine, which is structurally unrelated to DMI. In contrast,
      exposure of cells to the serotonin transporter-selective drug citalopram, or the
      NET substrate norepinephrine, had no effects on the binding of [3H]nisoxetine to
      NETs. The down-regulation of NETs was paralleled by a DMI-induced reduction in
      the uptake of [3H]norepinephrine in intact PC12 cells. It can be inferred from
      these data that inhibitors of the NET can down-regulate NETs directly, and do so
      in the absence of changes in the synaptic concentration of norepinephrine.

PMID- 8978720
TI  - Inhibitors of histamine methylation in brain promote formation of imidazoleacetic
      acid, which interacts with GABA receptors.
AB  - In brain, the precursor of imidazoleacetic acid (IAA), a GABAA agonist but a
      GABAC antagonist, is not known. In the periphery, IAA derives from oxidation of
      histamine. But in brain, histamine is thought to be metabolized solely by
      histamine methyltransferase (HMT), forming tele-methylhistamine (t-MH) and tele
      methylimidazoleacetic acid (t-MIAA). We showed that [3H]-histamine
      (intracerebroventricularly) could be converted to IAA in brains of rats, a
      process increased by inhibition of HMT. This demonstrated that brain can oxidize
      histamine and suggested that endogenous histamine might also be oxidized if HMT
      activity were reduced. We examined in rat cerebral cortex, effects of the
      following HMT inhibitors (mg/kg i.p.): metoprine (10), tacrine (10), velnacrine
      (10, 30), and physostigmine (1,2). Tacrine was a potent inhibitor (Ki
      approximately 22 nM). To measure histamine in tissue that contained HMT
      inhibitors, we developed a gas chromatography-mass spectrometry method. After 2
      h, all drugs reduced endogenous levels of t-MH and t-MIAA and increased levels of
      histamine and IAA. Our results show that inhibition of HMT promotes oxidation of
      histamine in brain, probably by shunting histamine to an alternative metabolic
      pathway. Formation of IAA provides a novel interaction between histaminergic and
      GABAergic systems in brain. Accumulation of IAA should be considered when
      inhibitors of HMT are used to probe brain histamine function.

PMID- 8978721
TI  - Real-time measurement of electrically evoked extracellular dopamine in the
      striatum of freely moving rats.
AB  - The real-time measurement of electrically evoked dopamine was established in
      brain extracellular fluid of freely moving rats. Dopamine was monitored by fast
      scan cyclic voltammetry at carbon fiber microelectrodes lowered into the striatum
      by means of a detachable micromanipulator. A stimulating electrode, previously
      implanted in the substantia nigra, was used to evoke striatal dopamine efflux.
      Evoked extracellular dopamine was both current and frequency dependent. When low
      current intensities (+/-125 microA) and frequencies (10-20 Hz) were applied,
      detectable levels of dopamine were elicited without a perceptible behavioral
      response. Reproducible concentrations of extracellular dopamine could be evoked
      in the same rat for at least 2 months. These concentrations, moreover, were
      significantly higher in freely moving rats compared with rats anesthetized with
      Equithesin. Analysis of measured curves for dopamine uptake and release rates
      revealed that anesthesia inhibits release but does not affect uptake. It is
      concluded that (a) fast-scan cyclic voltammetry at carbon fiber microelectrodes
      is a viable technique for the measurement of electrically evoked dopamine in
      brain extracellular fluid of freely moving rats, (b) it is possible to determine
      in situ rate constants for dopamine release and uptake from these temporally and
      spatially resolved measurements of levels of dopamine, and (c) transient changes
      in extracellular dopamine levels elicited by electrical stimulation are affected
      by anesthesia.

PMID- 8978722
TI  - Dual modulation of dopamine release from anterior nucleus accumbens through
      cholecystokinin-B receptor subsites.
AB  - Previous binding studies have suggested the existence of two affinity states for
      cholecystokinin-B (CCK-B) receptor. One study, using BC 197 and BC 264, two
      highly selective CCK-B agonists, has shown that BC 197 is selective for one
      subsite, B1, and that BC 264 has the same affinity for the two subsites, B1 and
      B2. Therefore, the possible involvement of CCK-B subsites in the modulation of
      endogenous dopamine (DA) release from slices of the anterior part of the nucleus
      accumbens was investigated with these two agonists in order to associate a
      functional response with activation of each subsite. The selective B1 agonist BC
      197 produced a dose-dependent increase of 35 mM K(+)-stimulated DA release. In
      contrast, at a low concentration (20 nM), BC 264 inhibited the K(+)-evoked DA
      release, whereas at a higher concentration (1 microM), it stimulated the DA
      release. These two opposing effects were suppressed by the CCK-B antagonist PD
      134,308, but not by the CCK-A antagonist L-364,718 and were not prevented by
      tetrodotoxin, a Na(+)-channel blocker. Moreover, BC 264 at 20 nM, in the presence
      of PD-134,308 at a concentration that would block the B2 subsites (0.1 nM),
      increased the evoked DA release. All together, these results support further the
      existence of distinct CCK-B subsites and suggest that, in the anterior nucleus
      accumbens, their stimulation mediates opposite effects on K(+)-stimulated DA
      release via a presynaptic mechanism.

PMID- 8978723
TI  - Calcium/calmodulin-dependent kinase II phosphorylates Drosophila visual arrestin.
AB  - Light activation of rhodopsin in the Drosophila photoreceptor induces a G protein
      coupled signaling cascade that results in the influx of Ca2+ into the
      photoreceptor cells. Immediately following light activation, phosphorylation of a
      photoreceptor-specific protein, phosrestin I, is detected. Strong sequence
      similarity to mammalian arrestin and electroretinograms of phosrestin mutants
      suggest that phosrestin I is involved in light inactivation. We are interested in
      identifying the protein kinase responsible for the phosphorylation of phosrestin
      I to link the transmembrane signaling to the light-adaptive response. Type II
      Ca2+/calmodulin-dependent kinase is one of the major classes of protein kinases
      that regulate cellular responses to transmembrane signals. We show here that
      partially purified phosrestin I kinase activity can be immunodepleted and
      immunodetected with antibodies to Ca2+/calmodulin-dependent kinase II and that
      the kinase activity exhibits regulatory properties that are unique to
      Ca2+/calmodulin-dependent kinase II such as Ca2+ independence after
      autophosphorylation and inhibition by synthetic peptides containing the
      Ca2+/calmodulin-dependent kinase II autoinhibitory domain. We also show that
      Ca2+/calmodulin-dependent kinase KII activity is present in Drosophila eye
      preparations. These results are consistent with our hypothesis that
      Ca2+/calmodulin-dependent kinase II phosphorylates phosrestin I. We suggest that
      Ca2+/calmodulin-dependent kinase II plays a regulatory role in Drosophila
      photoreceptor light adaptation.

PMID- 8978724
TI  - Coloboma hyperactive mutant mice exhibit regional and transmitter-specific
      deficits in neurotransmission.
AB  - The mouse mutant coloboma (Cm/+), which exhibits profound spontaneous
      hyperactivity and bears a deletion mutation on chromosome 2, including the gene
      encoding synaptosomal protein SNAP-25, has been proposed to model aspects of
      attention-deficit hyperactivity disorder. Increasing evidence suggests a crucial
      role for SNAP-25 in the release of both classical neurotransmitters and
      neuropeptides. In the present study, we compared the release of specific
      neurotransmitters in vitro from synaptosomes and slices of selected brain regions
      from Cm/+ mice with that of +/+ mice. The release of dopamine (DA) and serotonin
      (5-HT) from striatum, and of arginine vasopressin and corticotropin-releasing
      factor from hypothalamus and amygdala is calcium-dependent. Glutamate release
      from and content in cortical synaptosomes of Cm/+ mice are greatly reduced, which
      might contribute to the learning deficits in these mutants. In dorsal striatum of
      Cm/+ mutants, but not ventral striatum, KCl-induced release of DA is completely
      blocked and that of 5-HT is significantly attenuated, suggesting that striatal DA
      and 5-HT deficiencies may be involved in hyperactivity. Further, although
      acetylcholine failed to induce hypothalamic corticotropin-releasing factor
      release from Cm/+ slices, restraint stress increased plasma corticosterone levels
      in Cm/+ mice to a significantly higher level than in +/+ mice, suggesting an
      important role for arginine vasopressin in hypothalamic-pituitary-adrenal axis
      activation. These results suggest that reduced SNAP-25 expression may contribute
      to a region-specific and neurotransmitter-specific deficiency in neurotransmitter
      release.

PMID- 8978725
TI  - A novel regulation of expression of the alpha-subunit of the G stimulatory
      protein by dopamine via D1 dopamine receptors.
AB  - Exposure of human neuroblastoma SK-N-MC cells to 100 microM dopamine (DA) for 72
      h caused 70% loss of immunodetectable membrane-bound levels of the alpha-subunit
      of Ga. The loss in Gs alpha was accompanied by reduced (64.3 +/- 0.35% of control
      values) NaF-mediated stimulation of adenylyl cyclase and was independent of
      accumulated cyclic AMP (cAMP) levels, because neither forskolin nor dibutyryl
      cAMP treatment of cells mimicked the DA-induced effects. The reduction in Gs
      alpha content was manifest at the transcriptional level; Gs alpha mRNA levels
      were attenuated to 56.5 +/- 10% of control values after a 24-h treatment of cells
      with 100 microM DA. The concentration of DA required to produce the half-maximal
      decrease of Gs alpha mRNA content was 20 nM, similar to the high-affinity binding
      value (8.5 nM) of DA to D1 sites. Gs alpha mRNA levels were also attenuated (52
      +/- 3.5% of control values) by the D1-selective agonist SKF R-38393 but not by
      forskolin or dibutyryl cAMP. Attenuation of Gs alpha mRNA levels by agonists was
      blocked by the D1-selective antagonist SCH 23390. Stimulation of adenylyl cyclase
      inhibitory DA receptors, which are coexpressed in these cells, failed to down
      regulate Gs alpha mRNA, indicating that regulation of Gs alpha mRNA expression
      occurs specifically through chronic stimulation of D1 DA receptors.

PMID- 8978726
TI  - Serotonin stimulation of 5-HT4 receptors indirectly enhances in vivo dopamine
      release in the rat striatum.
AB  - Serotonin (5-HT) applied at 1, 3, and 10 microM into the striatum of halothane
      anesthetized rats by in vivo microdialysis enhanced dopamine (DA) outflow up to
      173, 283, and 584% of baseline values, respectively. The 5-HT effect was
      partially reduced by 1 or 10 microM GR 125,487, a 5-HT4 antagonist, and by 100
      microM DAU 6285, a 5-HT3/4 antagonist, whereas the 5-HT1/2/6 antagonist
      methiothepin (50 microM) was ineffective. In the presence of tetrodotoxin the
      effect of 1 microM 5-HT was not affected by 5-HT4 antagonists. In addition,
      tetrodotoxin abolished the increase in DA release induced by the 5-HT4 agonist
      (S)- zacopride (100 microM). In striatal synaptosomes, 1 and 10 microM 5-HT
      increased the outflow of newly synthesized [3H]DA up to 163 and 635% of control
      values, respectively. The 5-HT4 agonists BIMU 8 and (S)-zacopride (1 and 10
      microM) failed to modify [3H]DA outflow, whereas 5- methoxytryptamine (5-MeOT) at
      10 microM increased it (62%). In prelabeled [3H]DA synaptosomes, 1 microM 5-HT,
      but not (S)-zacopride (1 and 10 microM), increased [3H]DA outflow. DAU 6285 (10
      microM) failed to modify the enhancement of newly synthesized [3H]DA outflow
      induced by 5-MeOT or 5-HT (1 microM), whereas the effect of 5-HT was reduced to
      the same extent by the DA reuptake inhibitor nomifensine (1 microM) alone or in
      the presence of DAU 6285. These results show that striatal 5-HT4 receptors are
      involved in the 5-HT-induced enhancement of striatal DA release in vivo and that
      they are not located on striatal DA terminals.

PMID- 8978727
TI  - Gene-based neurotransmitter modulation in cerebellar granule neurons.
AB  - The human glutamic acid decarboxylase (GAD) gene was transferred into rat
      cerebellar granule neurons. Following adenoviral-mediated gene transfer, nearly
      100% of the neurons had transgene expression that persisted for the duration of
      their survival in culture. GABA levels were elevated both in the growth media and
      in lysates of GAD-modified granule neurons. In GAD-modified neurons,
      extracellular GABA levels steadily increased with time, whereas intracellular
      GABA levels peaked 10 days after gene transfer. GAD-modified neurons released
      both glutamate and GABA into the surrounding media before and after potassium
      induced stimulation, but only the release of glutamate was sensitive to potassium
      stimulation. These data suggest that glutamatergic neurons, which initially
      contained no detectable GABA, can be genetically modified to release GABA
      constitutively.

PMID- 8978728
TI  - Avian melatonin synthesis: photic and circadian regulation of serotonin N
      acetyltransferase mRNA in the chicken pineal gland and retina.
AB  - The circadian rhythms in melatonin production in the chicken pineal gland and
      retina reflect changes in the activity of serotonin N-acetyltransferase
      (arylalkylamine N-acetyltransferase; AA-NAT; EC 2.3.1.87). Here we determined
      that the chicken AA-NAT mRNA is detectable in follicular pineal cells and retinal
      photoreceptors and that it exhibits a circadian rhythm, with peak levels at
      night. AA-NAT mRNA was not detected in other tissues. The AA-NAT mRNA rhythm in
      the pineal gland and retina persists in constant darkness (DD) and constant
      lighting (LL). The amplitude of the pineal mRNA rhythm is not decreased in LL.
      Light appears to influence the phase of the clock driving the rhythm in pineal AA
      NAT mRNA in two ways: The peak is delayed by approximately 6 h in LL, and it is
      advanced by > 4 h by a 6-h light pulse late in subjective night in DD. Nocturnal
      AA-NAT mRNA levels do not change during a 20-min exposure to light, whereas this
      treatment dramatically decreases AA-NAT activity. These observations suggest that
      the rhythmic changes in chicken pineal AA-NAT activity reflect, at least in part,
      clock-generated changes in mRNA levels. In contrast, changes in mRNA content are
      not involved in the rapid light-induced decrease in AA-NAT activity.

PMID- 8978729
TI  - Phorbol esters increase dopamine transporter phosphorylation and decrease
      transport Vmax.
AB  - Sodium- and chloride-coupled transport of dopamine from synapses into presynaptic
      terminals plays a key role in terminating dopaminergic neurotransmission.
      Regulation of the function of the dopamine transporter, the molecule responsible
      for this translocation, is thus of interest. The primary sequence of the dopamine
      transporter contains multiple potential phosphorylation sites, suggesting that
      the function of the transporter could be regulated by phosphorylation. Previous
      work from this laboratory has documented that phorbol ester activation of protein
      kinase C (PKC) decreases dopamine transport Vmax in transiently expressing COS
      cells. In the present report, we document in vivo phosphorylation of the rat
      dopamine transporter stably expressed in LLC-PK1, cells and show that
      phosphorylation is increased threefold by phorbol esters. Dopamine uptake is also
      regulated by phorbol esters in these cells; phorbol 12-myristate 13-acetate (PMA)
      reduces transport Vmax by 35%. Parallels between the time course, concentration
      dependency, and staurosporine sensitivity of alterations in transporter
      phosphorylation and transporter Vmax suggest that dopamine transporter
      phosphorylation involving PKC could contribute to this decreased transporter
      function. Phosphorylation of the dopamine transporter by PKC or by a PKC
      activated kinase could be involved in rapid neuroadaptive processes in
      dopaminergic neurons.

PMID- 8978730
TI  - Intranasal administration of the dopaminergic agonists L-DOPA, amphetamine, and
      cocaine increases dopamine activity in the neostriatum: a microdialysis study in
      the rat.
AB  - The effectiveness of intranasal drug administration to stimulate central neuronal
      systems is well known from drug addiction and has also been considered as an
      alternative pharmacokinetic approach to treat brain disorders such as Parkinson's
      disease. In the present study, the possible neurochemical effects of intranasal
      administration of the psychostimulants cocaine and amphetamine and of the
      antiparkinsonian drug L-DOPA were analyzed. By using in vivo microdialysis in the
      urethane-anesthetized rat, it was found that unilateral intranasal administration
      of either of the psychostimulants led to huge and rapid increases of
      extracellular dopamine levels in the neostriatum followed by decreases of its
      metabolites dihydroxyphenylacetic acid and homovanillic acid. Furthermore,
      intranasal administration of L-DOPA, but not of the saline vehicle, also led to
      increased extracellular levels of neostriatal dopamine and to increases of its
      metabolites. Because the effect of intranasal L-DOPA on neostriatal dopamine was
      observed only ipsilaterally but not contralaterally to the side of intranasal
      drug administration, it can be hypothesized that L-DOPA was not effective via
      passage through the circulation but may have acted through a neuronal or an
      extraneuronal route. These data provide neurochemical evidence that the
      intranasal route may not only be efficient in drug abuse, but may also be useful
      to target the brain therapeutically, as in the case of neurodegenerative brain
      disorders.

PMID- 8978731
TI  - Kainate-evoked release of adenosine from the hippocampus of the anaesthetised
      rat: possible involvement of free radicals.
AB  - Using microdialysis in the hippocampus of anaesthetised rats, the concentration
      of extracellular adenosine was estimated to be 0.8 microM. Kainic acid (0.1-25
      mM) in the perfusate evoked a concentration-dependent release of adenosine with
      an EC50 of 940 microM. Two 5-min pulses of 1 mM kainic acid in the perfusate
      increased the dialysate levels with an S2/S1 ratio of 0.52 +/- 0.03. Kainate
      evoked release of adenosine was reduced significantly by 10 microM tetrodotoxin
      and by a kappa-receptor agonist, U50, 488H (100 microM). The S2/S1 ratio was
      reduced by 4.5 microM 6-cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA receptor
      antagonist, but not by the NMDA receptor blockers (+)-MK-801 (dizocilpine; 100
      microM) or (+/-)-2-amino-5-phosphonopentanoic acid (1 mM), indicating a non-NMDA
      receptor-mediated process. The S2/S1 ratio was also reduced significantly by 10
      mM ascorbic acid, 10 mM glutathione (a scavenger of hydroperoxides), and 1 mM
      oxypurinol (a xanthine oxidase inhibitor), indicating the possible involvement of
      free radicals. Neither the adenosine A1 receptor antagonist 8-cyclopentyl-1,3
      dimethylxanthine (100 microM) nor the A1 adenosine receptor agonist R(-)-N6-(2
      phenylisopropyl)adenosine (100 microM) affected release. Adenosine release evoked
      by kainic acid is therefore mediated by activation of non-NMDA receptors and may
      involve the propagation of action potentials and the production of free radicals.

PMID- 8978732
TI  - Altered mu-opiate receptor-G protein signal transduction following chronic
      morphine exposure.
AB  - This laboratory has demonstrated that the longitudinal muscle/myenteric plexus
      (LMMP) preparation manifests pleiotropic responses to opioid agonists. For
      example, the mu-selective opiate receptor agonist sufentanil can produce a
      naloxone-reversible increase or decrease in the electrically stimulated formation
      of cyclic AMP, depending on its concentration. The present study demonstrates
      that the sufentanil facilitation and inhibition of stimulated cyclic AMP
      formation are mediated via Gs- and Gi-like G proteins, respectively. Inactivation
      of Gi (via pertussis toxin) not only abolishes sufentanil inhibition of cyclic
      AMP formation but also unmasks a facilitory effect. The latter response is
      eliminated following treatment with cholera toxin. In tolerant/dependent LMMP
      tissue, previously inhibitory concentrations of sufentanil produce a facilitation
      of cyclic AMP formation. However, this unmasked facilitory effect is resistant to
      cholera toxin. Thus, although inactivation of the inhibitory signal transduction
      pathway (via pertussis toxin) is sufficient to unmask excitatory sufentanil
      effects in opiate naive preparations, this mechanism cannot explain the reversal
      of sufentanil inhibition to facilitation that is observed in tolerant/dependent
      tissue. Instead, the chronic morphine-induced emergence of a mu-opiate receptor
      coupled facilitory pathway that is either not expressed or not fully manifest in
      opiate naive LMMP tissue is suggested.

PMID- 8978733
TI  - A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in
      disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide.
AB  - Peroxidation of membrane lipids results in release of the aldehyde 4
      hydroxynonenal (HNE), which is known to conjugate to specific amino acids of
      proteins and may alter their function. Because accumulating data indicate that
      free radicals mediate injury and death of neurons in Alzheimer's disease (AD) and
      because amyloid beta-peptide (A beta) can promote free radical production, we
      tested the hypothesis that HNE mediates A beta 25-35-induced disruption of
      neuronal ion homeostasis and cell death. A beta induced large increases in levels
      of free and protein-bound HNE in cultured hippocampal cells. HNE was neurotoxic
      in a time- and concentration-dependent manner, and this toxicity was specific in
      that other aldehydic lipid peroxidation products were not neurotoxic. HNE
      impaired Na+, K(+)-ATPase activity and induced an increase of neuronal
      intracellular free Ca2+ concentration. HNE increased neuronal vulnerability to
      glutamate toxicity, and HNE toxicity was partially attenuated by NMDA receptor
      antagonists, suggesting an excitotoxic component to HNE neurotoxicity.
      Glutathione, which was previously shown to play a key role in HNE metabolism in
      nonneuronal cells, attenuated the neurotoxicities of both A beta and HNE. The
      antioxidant propyl gallate protected neurons against A beta toxicity but was less
      effective in protecting against HNE toxicity. Collectively, the data suggest that
      HNE mediates A beta-induced oxidative damage to neuronal membrane proteins,
      which, in turn, leads to disruption of ion homeostasis and cell degeneration.

PMID- 8978734
TI  - Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive
      Ca2+ channels: a possible involvement of free radicals.
AB  - Amyloid beta protein (A beta), the central constituent of senile plaques in
      Alzheimer's disease (AD) brain, is known to exert toxic effects on cultured
      neurons. The role of the voltage-sensitive Ca2+ channel (VSCC) in beta (25-35)
      neurotoxicity was examined using rat cultured cortical and hippocampal neurons.
      When L-type VSCCs were blocked by application of nimodipine, beta (25-35)
      neurotoxicity was attenuated, whereas application of omega-conotoxin GVIA (omega
      CgTX-GVIA) or omega-agatoxin IVA (omega-Aga-IVA), the blocker for N- or P/Q-type
      VSCCs, had no effects. Whole-cell patch-clamp studies indicated that the Ca2+
      current density of beta (25-35)-treated neurons is about twofold higher than that
      of control neurons. Also, beta (25-35) increased Ca2+ uptake, which was sensitive
      to nimodipine. The 2', 7'-dichlorofluorescin diacetate assay showed the ability
      of beta (25-35) to produce reactive oxygen species. Nimodipine had no effect on
      the level of free radicals. In contrast, vitamin E, a radical scavenger, reduced
      the level of free radicals, neurotoxicity, and Ca2+ uptake. These results suggest
      that beta (25-35) generates free radicals, which in turn, increase Ca2+ influx
      via the L-type VSCC, thereby inducing neurotoxicity.

PMID- 8978735
TI  - Long-term expression of Fos-related antigen and transient expression of delta
      FosB associated with seizures in the rat hippocampus and striatum.
AB  - Systemic administration of kainic acid (KA), an analogue of glutamic acid, causes
      limbic seizures and pathophysiological changes in adult rats that are very
      similar to human temporal lobe epilepsy. One of the earliest changes in gene
      expression after treatment with KA is the induction of immediate-early genes. The
      fos and jun families are frequently studied immediate-early genes that are
      induced by KA. Several groups, including ours, have recently reported that a 35
      kDa Fos-related antigen (FRA) is induced for a protracted time by various
      stimuli. It has been suggested that this FRA is delta FosB, which has a molecular
      mass of approximately 35 kDa. The present study characterizes the long-term
      expression of FRA and delta FosB after systemic treatment with KA.
      Immunocytochemistry and western blot analysis using an antibody that cross-reacts
      with all known FRAs showed that a 35-kDa FRA was induced at high levels in both
      the hippocampus and striatum for up to 1 month by KA. A semiquantitative PCR
      analysis showed that delta FosB was induced by KA, but its expression lasted for
      only 6 h. This result was also verified by northern blot analysis. These results
      suggested that the 35-kDa FRA with long-term elevated levels seen with western
      blot analysis and immunocytochemistry is a new species of the FRA and not delta
      FosB. The long-term expression of FRA in both the hippocampus and striatum may be
      associated with the pathophysiological changes after KA administration.

PMID- 8978736
TI  - Quantification of local de novo synthesis versus blood contributions to
      quinolinic acid concentrations in brain and systemic tissues.
AB  - The source of the neurotoxin quinolinic acid (QUIN) in brain and systemic tissues
      under normal and pathologic circumstances reflects either de novo synthesis from
      L-tryptophan and other precursors, or entry of QUIN itself from the blood. To
      quantify the relative contributions of blood- versus tissue-derived QUIN, [13C7]
      QUIN was infused subcutaneously via osmotic pumps (0.55 microliter/h, 30 mM) in
      gerbils, and the fraction of QUIN in tissue (Tl; measured in tissue homogenates)
      derived from blood (Bl; measured in serum) was calculated by the formula
      ([13C7]QUINTi/QUINTi)/([13C7]QUINBl/ QUINBl). In controls, blood QUIN contributed
      38-49% of QUIN in brain, 70% in CSF, between 40 and 70% in kidney, heart, and
      skeletal muscle, but < 5% in spleen, lung, liver, and intestine. Systemic
      endotoxin (450 micrograms/kg) increased blood, brain, CSF, and systemic tissue
      QUIN levels. Notably, the relative proportion of QUIN derived from blood in
      brain, spleen, lung, and intestine was unchanged by endotoxin, but increased in
      kidney, heart, and skeletal muscle. In contrast, cerebral ischemic injury (10 min
      of bilateral carotid artery occlusion) increased regional brain QUIN
      concentrations at 4 days post ischemia, with a proportional increase in the
      amount of QUIN derived from de novo synthesis by brain tissue. In the blood and
      systemic tissues of postischemic gerbils, there were no changes in systemic
      tissue or blood QUIN levels, or changes in the relative proportions of blood-
      versus systemic tissue-derived QUIN. These results establish that the brain
      normally synthesizes QUIN, that the blood is a significant source of QUIN in
      controls and during acute systemic immune activation, and that the rate of QUIN
      formation by brain tissue increases in conditions of brain and systemic immune
      activation.

PMID- 8978737
TI  - Effect of Ca2+ on in vitro astrocyte injury.
AB  - Current literature suggests that a massive influx of Ca2+ into the cells of the
      CNS induces cell damage associated with traumatic brain injury (TBI). Using an in
      vitro model for stretch-induced cell injury developed by our laboratory, we have
      investigated the role of extracellular Ca2+ in astrocyte injury. The degree of
      injury was assessed by measurement of propidium iodide uptake and release of
      lactate dehydrogenase. Based on results of in vivo models of TBI developed by
      others, our initial hypothesis was that decreasing extracellular Ca2+ would
      result in a reduction in astrocyte injury. Quite unexpectedly, our results
      indicate that decreasing extracellular Ca2+ to levels observed after in vivo TBI
      increased astrocyte injury. Elevating the extracellular Ca2+ content to twofold
      above physiological levels (2 mM) produced a reduction in cell injury. The
      reduction in injury afforded by Ca2+ could not be mimicked with Ba2+, Mn2+, Zn2+,
      or Mg2+, suggesting that a Ca(2+)-specific mechanism is involved. Using 45Ca2+,
      we demonstrate that injury induces a rapid influx of extracellular Ca2+ into the
      astrocyte, achieving an elevation in total cell-associated Ca2+ content two- to
      threefold above basal levels. Pharmacological elevation of intracellular Ca2+
      levels with the Ca2+ ionophore A23187 or thapsigargin before injury dramatically
      reduced astrocyte injury. Our data suggest that, contrary to popular assumptions,
      an elevation of total cell-associated Ca2+ reduces astrocyte injury produced by a
      traumatic insult.

PMID- 8978738
TI  - Reduced [3H]cyclic AMP binding in postmortem brain from subjects with bipolar
      affective disorder.
AB  - Findings of increased Gs alpha levels and forskolin-stimulated adenylyl cyclase
      activity in selective cerebral cortical postmortem brain regions in bipolar
      affective disorder (BD) implicate increased cyclic AMP (cAMP)-mediated signaling
      in this illness. Accumulating evidence suggests that intracellular levels of cAMP
      modulate the abundance and disposition of the regulatory subunits of cAMP
      dependent protein kinase (cAMP-dPK). Thus, in the present study, we tested
      further whether hyperfunctional Gs alpha-linked cAMP signaling occurs in BD by
      determining [3H]cAMP binding, a measure of the levels of regulatory subunits of
      cAMP-dPK, in cytosolic and membrane fractions from discrete brain regions of
      postmortem BD brain. Specific [3H]cAMP (5 nM) binding was determined in autopsied
      brain obtained from 10 patients with DSM-III-R diagnoses of BD compared with age-
      and postmortem delay-matched controls. [3H]cAMP binding was significantly reduced
      across all brain regions in cytosolic fractions of BD frontal (-22%), temporal (
      23%), occipital (-22%) and parietal (-15%) cortex, cerebellum (-36%), and
      thalamus (-13%) compared with controls, but there were no differences in [3H]cAMP
      binding in the membrane fractions from these same regions. These results suggest
      that changes occur in the cAMP-dPK regulatory subunits in BD brain, possibly
      resulting from increased cAMP signaling. The possibility that antemortem lithium
      and/or other mood stabilizer treatment may contribute to the above changes,
      however, cannot be ruled out.

PMID- 8978739
TI  - Neurochemical changes in the cerebral cortex of treated and untreated
      hydrocephalic rat pups quantified with in vitro 1H-NMR spectroscopy.
AB  - The pathophysiology of infantile hydrocephalus is poorly understood, and shunt
      treatment does not always lead to a normal neurological outcome. To investigate
      some of the neurochemical changes in infantile hydrocephalus and the response to
      shunt treatment, we have used high-resolution 1H-NMR spectroscopy to analyze
      extracts of cerebral cortex from H-Tx rats, which have inherited hydrocephalus
      with an onset in late gestation. Hydrocephalic rats and rats with shunts placed
      at either 4 or 12 days after birth were studied at 21 days after birth, together
      with age-matched control littermates. In hydrocephalic rats there was a 46-62%
      reduction in the following compounds: myo-inositol, creatine, choline-containing
      compounds, N-acetyl aspartate, taurine, glutamine, glutamate, aspartate, and
      alanine. Phosphocreatine, glycine, GABA, and lactate were also reduced but not
      significantly. These changes are consistent with neuronal atrophy rather than
      ischemic damage. In hydrocephalic rats that received shunt treatment at 4 days,
      there were no significant reductions in any chemicals, indicating a normal
      complement of neurons. However, some compounds, particularly taurine, were
      elevated above control. After treatment at 12 days, N-acetyl aspartate and
      aspartate remained significantly reduced, suggesting continued neuronal
      deficiency.

PMID- 8978740
TI  - Effect of pentylenetetrazole-induced kindling on acetylcholine release in the
      hippocampus of freely moving rats.
AB  - The role of gamma-aminobutyric acid (GABA) modulation of septohippocampal
      cholinergic neurons in kindling was investigated. Hippocampal acetylcholine
      release was evaluated with the microdialysis technique in freely moving rats
      either after acute administration of isoniazid (an inhibitor of GABA synthesis)
      or pentylenetetrazole (PTZ) (a blocker of the GABAA receptor-associated Cl-
      channel) or after chronic administration of PTZ. Short-term treatment with PTZ (5
      50 mg/kg, i.p.) or isoniazid (150-250 mg/kg, s.c.) increased hippocampal
      acetylcholine release in a dose-dependent manner. In contrast, the basal
      concentration of acetylcholine in the dialysate from the hippocampus of rats
      chronically treated with PTZ (kindled animals) was significantly reduced relative
      to that of vehicle-treated rats (2.39 +/- 0.21 vs. 4.2 +/- 0.31 pmol per 20-min
      sample; p < 0.01). Moreover, the release of acetylcholine was markedly more
      sensitive to the effect of a challenge injection of PTZ (10 or 20 mg/kg, i.p.) in
      kindled rats than in naive rats or rats chronically treated with vehicle.
      Abecarnil, a selective benzodiazepine receptor agonist with marked anticonvulsant
      activity, was administered together with chronic PTZ to evaluate whether
      persistent activation of GABAA receptors and suppression of seizures during
      kindling might affect the sensitivity of septohippocampal cholinergic neurons to
      a challenge dose of PTZ. Abecarnil (1 mg/kg, i.p.) administered 40 min before
      each PTZ injection neither antagonized the decrease in basal acetylcholine
      release (2.26 +/- 0.19 pmol per 20-min sample) nor prevented the development of
      kindling. In contrast, abecarnil prevented the chronic PTZ-induced increase in
      the sensitivity of acetylcholine release to a challenge dose of PTZ. These
      results provide novel in vivo data concerning the role of hippocampal
      acetylcholine function in the development of kindling and potentially in the
      learning and memory deficits associated with this phenomenon.

PMID- 8978741
TI  - Neuroprotective effect of somatostatin on nonapoptotic NMDA-induced neuronal
      death: role of cyclic GMP.
AB  - Somatostatin (SRIF) exerts a modulatory function on neuronal transmission in the
      CNS. It has been proposed that a reduction of calcium currents is the major
      determinant of the inhibitory activity of this peptide on synaptic transmission.
      Because the neurotoxicity induced by activation of the NMDA subtype of glutamate
      receptor is mediated through excessive Ca2+ influx, we investigated whether SRIF
      counteracted NMDA-induced neuronal cell death. Neurons from embryonic rat
      cerebral cortex were cultured for 7-10 days and then exposed to 0.5 and 1 mM NMDA
      for 24 h. The neuronal viability, as assessed by the colorimetric method,
      decreased by 40 and 60%, respectively, compared with the control condition.
      Morphological and biochemical evidence indicated that cell death occurred by
      necrosis and not through an apoptotic mechanism. SRIF (0.5-10 microM),
      simultaneously applied with excitatory amino acid, significantly reduced in a
      dose-dependent manner the neurotoxic effect of NMDA but not that of KA (0.25-0.5
      mM). GABA (10 microM) partially protected neurons to a similar extent from NMDA-
      or KA-induced toxicity. SRIF type 2 receptor agonists, octreotide (SMS 201-995;
      10 microM) and vapreotide (RC 160; 10 microM), did not influence the NMDA
      dependent neurotoxicity. The intracellular mechanism involved in SRIF
      neuroprotection was investigated. Pertussin toxin (300 ng/ml), a G protein
      blocker, antagonized the protective effect of SRIF on NMDA neurotoxicity.
      Furthermore, the neuroprotective effect of SRIF was mimicked by dibutyryl-cyclic
      GMP (10 microM), a cyclic GMP analogue, whereas 8-(4-chlorphenylthio)-cyclic AMP
      (10 microM), a cyclic AMP analogue, was ineffective. The cyclic GMP content was
      increased in a dose-dependent manner by SRIF (2.5-10 microM). Finally, both
      specific (Rp-8-bromoguanosine 3',5'-monophosphate, 10 microM) and nonspecific [1
      (5 isoquinolinylsulfonyl)-2-methylpiperazine (H7), 10 microM] cyclic GMP
      dependent protein kinase (cGMP-PK) inhibitors did not interfere with NMDA
      toxicity but substantially reduced SRIF neuroprotection. Our data suggest a
      selective neuroprotective role of SRIF versus NMDA-induced nonapoptotic neuronal
      death in cortical cells. This effect is likely mediated by cGMP-PK presumably by
      regulation of the intracellular Ca2+ level.

PMID- 8978742
TI  - Generation of reactive oxygen species by tyrosine hydroxylase: a possible
      contribution to the degeneration of dopaminergic neurons?
AB  - It has been suggested that idiopathic parkinsonism, characterized by a loss of
      dopaminergic neurons of the nigrostriatal pathway, is due to the intracellular
      generation of reactive oxygen species, generated by a nonenzymatic or enzymatic
      partial reduction of dioxygen. Based on in vitro studies of the iron-containing
      monooxygenase tyrosine hydroxylase (TH), evidence is presented that this enzyme
      system may also contribute to such an oxidative stress. Thus, the purified and
      Fe(2+)-reconstituted recombinant human enzyme shows a time- and temperature
      dependent partial uncoupling of the hydroxylation of L-tyrosine with the natural
      cofactor (6R)-tetrahydrobiopterin, resulting in the formation of H2O2. The degree
      of uncoupling of the hydroxylation reaction is significantly higher when certain
      substrate analogues, notably the 7-substituted isomer (7-tetrahydrobiopterin) of
      the natural cofactor, is used. In the presence of H2O2 and Fe2+, the addition of
      TH increases the production of the highly reactive.OH radical, probably via a
      Fenton type of reaction. It is not clear whether this in vitro reaction can
      mediate cellular injury in vivo. However, it is known that the distribution of TH
      in the central and peripheral nervous system often corresponds to that of the
      neuronal degeneration in idiopathic parkinsonism, a finding that is compatible
      with a pathogenetic effect of TH.

PMID- 8978743
TI  - Inhibition of beta-amyloid formation by haloperidol: a possible mechanism for
      reduced frequency of Alzheimer's disease pathology in schizophrenia.
AB  - Several reports have suggested that the frequency of Alzheimer's disease (AD)
      neuropathology is significantly reduced in elderly individuals with schizophrenia
      (SZ), and it has been proposed that medications used for treatment of SZ may be
      responsible. A central event in AD pathology is the formation of beta-amyloid (A
      beta) peptide, which is derived by enzymatic processing of its precursor protein.
      Haloperidol, an antipsychotic medication commonly used in the treatment of SZ,
      can act as an inhibitor of select proteinases; hence, we examined the ability of
      this compound to inhibit A beta formation by cultured cells. Haloperidol and, to
      a lesser extent, droperidol inhibited A beta in a dose-dependent manner. These
      results may explain the apparent reduction of AD neuropathological changes in
      elderly patients with SZ as well as provide a possible mechanism for this
      difference.

PMID- 8978744
TI  - Portacaval shunting and hyperammonemia stimulate the uptake of L-[3H] arginine
      but not of L-[3H]nitroarginine into rat brain synaptosomes.
AB  - Elevated activities of nitric oxide synthase (NOS) have been reported previously
      in the brains of portacaval-shunted (PCS) rats, a model of chronic hepatic
      encephalopathy (HE). As L-arginine availability for nitric oxide synthesis
      depends on a specific uptake mechanism in neurons, we studied the kinetics of L
      [3H]-arginine uptake into synaptosomes prepared from the brains of PCS rats.
      Results demonstrate that L-arginine uptake is significantly increased in
      cerebellum (60%; p < 0.01), cerebral cortex (42%; p < 0.01), hippocampus (56%; p
      < 0.01), and striatum (51%; p < 0.01) of PCS rats compared with sham-operated
      controls. Hyperammonemia in the absence of portacaval shunting also stimulated
      the transport of L-[3H]arginine; kinetic analysis revealed that the elevated
      uptake was due to increased uptake capacity (Vmax) without any change in affinity
      (Km). Incubation of cerebellar synaptosomes with ammonium acetate for 10 min
      caused a dose-dependent stimulation of L-[3H]arginine uptake. Neither portacaval
      shunting nor hyperammonemia had any significant effect on the synaptosomal uptake
      of NG-nitro-L-[3H]arginine. These studies demonstrate that increased NOS activity
      observed in experimental HE may result from increased availability of L-arginine
      resulting from a direct stimulatory effect of ammonia on L-arginine transport.

PMID- 8978745
TI  - Key residues defining the mu-opioid receptor binding pocket: a site-directed
      mutagenesis study.
AB  - Structural elements of the rat mu-opioid receptor important in ligand receptor
      binding and selectivity were examined using a site-directed mutagenesis approach.
      Five single amino acid mutations were made, three that altered conserved residues
      in the mu, delta, and kappa receptors (Asn150 to Ala, His297 to Ala, and Tyr326
      to Phe) and two designed to test for mu/delta selectivity (Ile196 to Val and
      Val202 to Ile). Mutation of His297 in transmembrane domain 6 (TM6) resulted in no
      detectable binding with [3H]DAMGO (3H-labeled D-Ala2, N-Me-Phe4, Gly-ol5
      enkephalin), [3H]bremazocine, or [3H]ethylketocyclazocine. Mutation of Asn150 in
      TM3 produces a three- to 20-fold increase in affinity for the opioid agonists
      morphine, DAMGO, fentanyl, beta-endorphin1-31, JOM-13, deltorphin II, dynorphin1
      13, and U50,488, with no change in the binding of antagonists such as naloxone,
      naltrexone, naltrindole, and nor-binaltorphamine. In contrast, the Tyr326
      mutation in TM7 resulted in a decreased affinity for a wide spectrum of mu,
      delta, and kappa agonists and antagonists. Altering Val202 to Ile in TM4 produced
      no change on ligand affinity, but Ile196 to Val resulted in a four- to fivefold
      decreased affinity for the mu agonists morphine and DAMGO, with no change in the
      binding affinities of kappa and delta ligands.

PMID- 8978747
TI  - Corticosteroid modulation of signal transduction in the CATH.a cell line.
AB  - Noradrenergic neuronal networks originating in the locus coeruleus have been
      implicated in the stress response. In order to study this system in vitro, we
      have employed a locus coeruleus-like cell line, CATH.a, and have determined the
      effect of dexamethasone on receptor-mediated second messenger responses. The
      CATH.a cell line produced increases in intracellular cyclic AMP conversion in
      response to corticotrophin-releasing factor (EC50 = 6.93 +/- 1.26 nM, maximum
      conversion = 4.11 +/- 0.20%) and vasoactive intestinal polypeptide (EC50 = 240 +/
      40 nM, maximum conversion = 8.92 +/- 1.24%). Forskolin (10 microM) increased
      conversion from 0.48 +/- 0.05 to 6.39 +/- 0.38%. The alpha 2-adrenoceptor agonist
      5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) inhibited
      the forskolin response with an IC50 of 6.76 +/- 0.11 nM. Carbachol increased
      total 3H-labelled inositol phosphate accumulation to a maximum of 3.01 +/- 0.79
      fold basal (EC50 = 7.94 +/- 0.14 microM). Bradykinin produced a maximum 1.81 +/-
      0.05 fold basal stimulation of phosphoinositide hydrolysis (EC50 = 9.12 +/- 0.16
      nM). Both carbachol and bradykinin increased intracellular Ca2+ concentration
      probably via a combination of mobilisation of intracellular stores and gating of
      extracellular Ca2+. Incubation for 24 h with the glucocorticoid receptor agonist,
      dexamethasone (1 microM), significantly potentiated the receptor-mediated
      phosphoinositide responses to all the agents tested; however, of the receptor
      mediated increases in cyclic AMP conversion, only the vasoactive intestinal
      polypeptide response was potentiated. These results show that the CATH.a cell
      line displays some of the properties expected of locus coeruleus neurons and that
      glucocorticoid receptor stimulation selectively modulates receptor-mediated
      increases in second messenger formation.

PMID- 8978746
TI  - Nociceptin/orphanin FQ metabolism: role of aminopeptidase and endopeptidase
      24.15.
AB  - The endogenous opioid receptor-like1 (ORL1) ligand, nociceptin/orphanin FQ
      (FGGFTGARKSARKLANQ), a heptadecapeptide structurally resembling dynorphin A, has
      recently been identified. The wide distribution of ORL1 mRNA and
      nociceptin/orphanin FQ precursor in the CNS, particularly in the limbic system
      regions and in several areas known to be involved in pain perception, suggests
      that nociceptin/orphanin FQ is potentially endowed with various central
      functions. In general, activation and/or inactivation of regulatory peptides
      occur through the action of cell surface peptidases. The physiological mechanisms
      under which nociceptin/orphanin FQ is metabolized should lead to a better
      understanding of its physiological functions. Mouse brain cortical slices were
      incubated in medium containing the heptadecapeptide in the presence or in the
      absence of peptidase inhibitors. The critical sites of enzymatic cleavage are
      Phe1-Gly2, Ala7-Arg8, Ala11-Arg12, and Arg12-Lys13 bonds. The major role played
      by metallopeptidases was confirmed by the complete protection of metabolism in
      the presence of EDTA. Aminopeptidase N and endopeptidase 24.15 are the two main
      enzymes involved in nociceptin/orphanin FQ metabolism, whereas endopeptidase
      24.11 (involved in enkephalin [YGGFM(L)] catabolism) does not appear critically
      involved in nociceptin/orphanin FQ metabolism. The physiological relevance of
      aminopeptidase N and endopeptidase 24.15 in the heptadecapeptide metabolism
      remains to be determined.

PMID- 8978748
TI  - Brain-derived neurotrophic factor increases the stimulation-evoked release of
      glutamate and the levels of exocytosis-associated proteins in cultured cortical
      neurons from embryonic rats.
AB  - Differentiation and survival of neurons induced by neurotrophins have been widely
      investigated, but little has been reported about the long-term effect of brain
      derived neurotrophic factor (BDNF) on synaptic transmission. Among many steps of
      neurotransmission, one important step is regulated release of transmitters.
      Therefore, the release of glutamate and GABA from cortical neurons cultured for
      several days with or without BDNF was measured by an HPLC-fluorescence method.
      Although BDNF had little effect on the basal release of glutamate, high K(+)
      evoked release was greatly increased by BDNF. BDNF also tended to increase evoked
      release of GABA. Recently, several proteins involved in the step of "regulated
      release" have been identified. Thus, the effect of BDNF on the levels of these
      proteins was then investigated. Neurons were cultivated with or without BDNF,
      collected, and electrophoresed for western blotting. BDNF increased levels of
      synaptotagmin, synaptobrevin, synaptophysin, and rab3A, which were known as
      vesicle protein. Levels of syntaxin, SNAP-25, and beta-SNAP were also increased
      by BDNF. In addition, the numbers of cored and clear vesicles in nerve terminals
      or varicosities were also increased by BDNF. These results raise the possibility
      that BDNF increases regulated release of neurotransmitters through the up
      regulation of secretory mechanisms.

PMID- 8978749
TI  - Arginine-modulated receptor-activated calcium influx via a NO/cyclic GMP pathway
      in human SK-N-SH neuroblastoma cells.
AB  - The effects of arginine on calcium mobilization in human SK-N-SH neuroblastoma
      cells were examined. It was found that arginine potentiated an increase in
      carbachol-induced Ca2+ from the external Ca2+ influx as opposed to an internal
      Ca2+ release from intracellular pools. The potentiation effect of arginine on
      carbachol-induced calcium mobilization was mimicked by either 8-bromo cyclic GMP
      or sodium nitroprusside. In addition, it was found that arginine induced NO
      production and an increase in cyclic GMP. Moreover, arginine-induced
      potentiation, NO production, and cyclic GMP increases were all suppressed after
      the preincubation of cells with N-methyl-L-arginine or N-nitro-L-arginine, nitric
      oxide synthase inhibitor. It is suggested that the NO production and subsequent
      cyclic GMP elevation induced by arginine are responsible for the potentiation of
      carbachol-induced Ca2+ increase. Our results show the existence of a NO/cyclic
      GMP pathway and an interconnection of NO and Ca2+ signaling pathways in human SK
      N-SH neuroblastoma cells. We also observed that NO, which is produced by
      endothelial CPAE cells, has a modulating effect on cyclic GMP elevation in human
      SK-N-SH neuroblastoma cells. The intercellular communication role of NO and its
      cell-diffusing character may also affect the regulation of nonneuronal cells in
      their interactions with neuronal cells.

PMID- 8978750
TI  - Expression of microtubule-associated protein-2a and other novel microtubule
      associated protein-2 transcripts in human fetal spinal cord.
AB  - In human fetal spinal cord (HFSC), six additional microtubule-associated protein
      2 (MAP-2) transcripts are generated by alternative splicing of two recently
      described exons, exon 8 and exon 13. The following three translated proteins are
      detected by western blot analysis: MAP-2b expressing exon 8 (MAP-2b + 8; MAP-2a),
      MAP-2b expressing exon 13 (MAP-2b + 13), and MAP-2c expressing exon 8 and exon 13
      (MAP-2c + 8 + 13). The finding that MAP-2b + 8 is expressed in HFSC demonstrates
      for the first time the presence of MAP-2a in human fetal CNS. Immunocytochemical
      studies show that exon 8-specific antibody and exon 13-specific antibody stain
      independent and overlapping populations of neurons in the lumbar region of the
      HFSC. Antibody 13-immunopositive neurons have predominantly cytosolic staining,
      whereas in the antibody 8-immunoreactive neurons staining was observed in the
      cytosol, dendrites, and some synapses. The prenatal expression of MAP-2a, which
      has been used as a marker of synaptogenesis, not only demonstrates the presence
      of a mature MAP-2 isoform in HFSC, but suggests that MAP-2a is important during
      human fetal as well as postnatal synaptogenesis.

PMID- 8978751
TI  - Activation of protein kinase C-alpha and translocation of the myristoylated
      alanine-rich C-kinase substrate correlate with phorbol ester-enhanced
      noradrenaline release from SH-SY5Y human neuroblastoma cells.
AB  - The aim of this study was to investigate the mechanism by which short-term
      pretreatment with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA;
      100 nM) enhances noradrenaline (NA) release from the human neuroblastoma cell
      line SH-SY5Y. Subcellular fractionation and immunocytochemical studies
      demonstrated that an 8-min TPA treatment caused translocation of the alpha
      subtype of protein kinase C (PKC) from the cytosol to the plasma membrane. In
      contrast, TPA altered the distribution of PKC-epsilon from cytosolic and membrane
      associated to cytoskeleton- and membrane-associated. TPA had no effect on the
      cytosolic location of PKC-zeta. Subcellular fractionation studies also showed
      that the myristoylated alanine-rich C-kinase substrate (MARCKS), a major neuronal
      PKC substrate that has been implicated in the mechanism of neurotransmitter
      release, translocated from membranes to cytosol in response to an 8-min TPA
      treatment. Under these conditions the level of phosphorylation of MARCKS
      increased threefold. The ability of TPA to enhance NA release and to cause the
      translocation and phosphorylation of MARCKS was inhibited by the PKC inhibitor Ro
      31-8220 (10 microM). Selective down-regulation of PKC subtypes by prolonged
      exposure to phorbol 12,13-dibutyrate (100 nM) attenuated the TPA-induced
      enhancement of NA release and the translocation of MARCKS over an interval
      similar to that of down-regulation of PKC-alpha (but not -epsilon or -zeta).
      Thus, we have demonstrated a strong correlation between the translocation of
      MARCKS and the enhancement of NA release from SH-SY5Y cells due to the TPA
      induced activation of PKC-alpha.

PMID- 8978752
TI  - Characterization of CB1 receptors on rat neuronal cell cultures: binding and
      functional studies using the selective receptor antagonist SR 141716A.
AB  - This study was undertaken to characterize further the central cannabinoid
      receptors in rat primary neuronal cell cultures from selected brain structures.
      By using [3H]SR 141716A, the specific CB1 receptor antagonist, we demonstrate in
      cortical neurons the presence of a high density of specific binding sites (Bmax =
      139 +/- 9 fmol/mg of protein) displaying a high affinity (KD = 0.76 +/- 0.09 nM).
      The two cannabinoid receptor agonists, CP 55940 and WIN 55212-2, inhibited in a
      concentration-dependent manner cyclic AMP production induced by either 1 microM
      forskolin or isoproterenol with EC50 values in the nanomolar range (4.6 and 65 nM
      with forskolin and 1.0 and 5.1 nM with isoproterenol for CP 55940 and WIN 55212
      2, respectively). Moreover, in striatal neurons and cerebellar granule cells, CP
      55940 was also able to reduce the cyclic AMP accumulation induced by 1 microM
      forskolin with a potency similar to that observed in cortical neurons (EC50
      values of 3.5 and 1.9 nM in striatum and cerebellum, respectively). SR 141716A
      antagonized the CP 55940- and WIN 55212-2-induced inhibition of cyclic AMP
      accumulation, suggesting CB1 receptor-specific mediation of these effects on all
      primary cultures tested. Furthermore, CP 55940 was unable to induce mitogen
      activated protein kinase activation in either cortical or striatal neurons. In
      conclusion, our results show nanomolar efficiencies for CP 55940 and WIN 55212-2
      on adenylyl cyclase activity and no effect on any other signal transduction
      pathway investigated in primary neuronal cultures.

PMID- 8978753
TI  - Sequence and functional analysis of cloned guinea pig and rat serotonin 5-HT1D
      receptors: common pharmacological features within the 5-HT1D receptor subfamily.
AB  - This study was undertaken to investigate the pharmacology of cloned guinea pig
      and rat 5-hydroxytryptamine (serotonin; 5-HT)1D receptor sites. Guinea pig, rat,
      and mouse 5-HT1D receptor genes were cloned, and their amino acid sequences were
      compared with those of the human, dog, and rabbit. The overall amino acid
      sequence identity between these 5-HT1D receptors is high and varies between 86
      and 99%. The sequence homology is slightly more divergent (13-27%) in the N
      terminal extracellular region of these 5-HT1D receptors. Guinea pig and rat 5
      HT1D receptors, stably and separately expressed in rat C6 glial cells, are
      negatively coupled to cyclic AMP formation upon stimulation with agonists, as
      previously found for cloned human 5-HT1D receptor sites. The cyclic AMP data show
      some common pharmacological features for the 5-HT1D receptors of guinea pig, rat,
      and human: an almost similar rank order of potency for the investigated 5-HT1D
      receptor agonists, stereoselectivity for the binding affinity and agonist potency
      of R(+)-8-hydroxy-2-(di-n-propylamino)tetralin, and equal 5-HT1D receptor
      mediated antagonist potency for methiothepin and the 5-HT2 receptor antagonists
      ritanserin and ketanserin. In conclusion, the pharmacology of the cloned 5-HT1D
      receptor subtype seems, unlike the 5-HT1B receptor subtype, conserved among
      various mammal species such as the human, guinea pig, and rat.

PMID- 8978754
TI  - Implication of Ca(2+)-dependent protein tyrosine phosphorylation in carbachol
      induced phospholipase D activation in rat pheochromocytoma PC12 cells.
AB  - The mechanism for carbachol (CCh)-induced phospholipase D (PLD) activation was
      investigated in [3H]palmitic acid-labeled pheochromocytoma PC12 cells with
      respect to the involvement of protein tyrosine phosphorylation and Ca2+. PLD
      activity was assessed by measuring the formation of [3H]phosphatidylbutanol in
      the presence of 0.3% butanol. Pretreatment of cells with the tyrosine kinase
      inhibitors herbimycin A, genistein, and tyrphostin inhibited PLD activation by
      CCh. Western blot analysis revealed several apparent tyrosine-phosphorylated
      protein bands (111, 91, 84, 74, 65-70, 44, and 42 kDa) in PC12 cells treated with
      CCh. Phosphorylation of the 111-, 91-, 84-, and 65-70-kDa proteins peaked within
      1 min, and their time-dependent changes seemingly correlated with that of PLD
      activation. Others (74, 44MAPK, and 42MAPK kDa) were phosphorylated rather
      slowly, and maximal tyrosine phosphorylation was observed at 2 min. Herbimycin A
      inhibited PLD activity and tyrosine phosphorylation of four proteins (111, 91,
      84, and 65-70 kDa) in a preincubation time- and concentration-dependent fashion.
      In Ca(2+)-free buffer, CCh-induced [3H]phosphatidylbutanol formation and protein
      tyrosine phosphorylation were abolished. A Ca2+ ionophore, A23187, caused PLD
      activation and tyrosine phosphorylation of four proteins of 111, 91, 84, and 65
      70 kDa only in the presence of extracellular Ca2+. Extracellular Ca2+ dependency
      for CCh-induced PLD activation was well correlated with that for tyrosine
      phosphorylation of the four proteins listed above, especially the 111-kDa
      protein. These results suggest that Ca(2+)-dependent protein tyrosine
      phosphorylation is closely implicated in CCh-induced PLD activation in PC12
      cells.

PMID- 8978755
TI  - Energy stress-induced dopamine loss in glutathione peroxidase-overexpressing
      transgenic mice and in glutathione-depleted mesencephalic cultures.
AB  - The role of the glutathione system in protecting dopamine neurons from a mild
      impairment of energy metabolism imposed by the competitive succinate
      dehydrogenase inhibitor, malonate, was investigated in vitro and in vivo.
      Treatment of mesencephalic cultures with 10 microM buthionine sulfoxamine for 24
      h reduced total glutathione levels in the cultures by 68%. Reduction of cellular
      glutathione per se was not toxic to the dopamine population, but potentiated
      toxicity when the cultures were exposed to malonate. In contrast, transgenic mice
      overexpressing glutathione peroxidase (hGPE) that received an intrastriatal
      infusion of malonate (3 mumol) into the left side had significantly less loss of
      striatal dopamine than their hGPE-negative littermates when assayed 1 week
      following infusion. These studies demonstrate that manipulation of the
      glutathione system influences susceptibility of dopamine neurons to damage due to
      energy impairment. The findings may provide insight into the loss of dopamine
      neurons in Parkinson's disease in which defects in both energy metabolism and the
      glutathione system have been identified.

PMID- 8978756
TI  - The tau protein in human cerebrospinal fluid in Alzheimer's disease consists of
      proteolytically derived fragments.
AB  - Previous studies have shown that the levels of the microtubule-associated protein
      tau in the CSF of patients with Alzheimer's disease (AD) are elevated compared
      with age-matched controls. In spite of these findings, the nature of tau in CSF
      has not been well documented. In the present study, tau was immunoprecipitated
      from CSF of patients with AD or acute stroke, as well as normal elderly controls,
      followed by immunoblot analysis. In all cases, CSF tau consisted primarily of a
      band migrating at 26-28 kDa. In AD and stroke patients, several smaller tau
      fragments were also detected. No intact tau was detected in any of the CSF
      samples examined. Further immunoprecipitation studies showed that the majority of
      the tau fragments contained the amino terminus of the molecule. Treatment of CSF
      tau with alkaline phosphatase did not alter the electrophoretic properties of the
      fragments. These studies clearly demonstrate that CSF tau is truncated rather
      than intact.

PMID- 8978757
TI  - L-(-)-desmethylselegiline, a metabolite of selegiline [L-(-)-deprenyl], protects
      mesencephalic dopamine neurons from excitotoxicity in vitro.
AB  - Selegiline [L-(-)-deprenyl], a monoamine oxidase B inhibitor, has been used in
      the treatment of Parkinson's disease as a putative neuroprotective agent.
      Selegiline is metabolized rapidly in the gastrointestinal tract and liver to
      desmethylselegiline (DMS) and methamphetamine. We have previously shown that
      selegiline protects dopamine neurons in mesencephalic cultures from toxicity
      resulting from activation of glutamate receptors. In the present study we
      examined whether DMS has similar neuroprotective effects. Our data show that DMS
      protects dopamine neurons from N-methyl-D-aspartate receptor-mediated excitotoxic
      damage. The efficacy of DMS is greater than that of selegiline, as it can cause
      protection at lower concentrations and provide significantly greater levels of
      protection at the same concentrations. Our results suggest that DMS might be the
      active compound responsible for the neuroprotective properties of selegiline.

PMID- 8978758
TI  - Conformations of beta-amyloid in solution.

PMID- 8978759
TI  - Report of the first international workshop on human chromosome 10 mapping 1995.

PMID- 8978760
TI  - Report of the second international workshop on human chromosome 1 mapping 1995.

PMID- 8978761
TI  - Microdeletions in interval 6 of the Y chromosome detected by STS-PCR in 6 of 33
      patients with idiopathic oligo- or azoospermia.
AB  - It has been proposed that interval 6 of the human Y chromosome contains the gene
      or genes that control spermatogenesis (AZF, azoospermia factor). We have studied
      this region in 33 patients with oligo- or azoospermia, using PCR amplification of
      the YRRM1 (RBM1) gene and of 13 sequence-tagged sites (STSs), all mapping within
      interval 6. Six of the 33 patients showed no amplification of specific STSs,
      whereas there was no failure of amplification in normal male controls. We deduce
      that these six patients had microdeletions in interval 6 of the Y chromosome that
      correlated with the oligo- or azoospermia of these individuals. On biopsy of the
      testis, two of these patients showed a low number of germ cells, and four showed
      arrest with spermatides. We conclude that PCR amplification of Y-specific regions
      is a powerful and very sensitive tool for screening infertile men.

PMID- 8978762
TI  - Reassignment of the 92-kDa type IV collagenase gene (CLG4B) to human chromosome
      20.
AB  - The collagenase type IV B gene (CLG4B) was previously mapped to human chromosome
      16 by hybridization of a cDNA probe to DNAs from a somatic cell hybrid panel. We
      have relocalized CLG4B to chromosome 20 based on three different lines of
      evidence: screening a somatic cell hybrid mapping panel, fluorescence in situ
      hybridization (FISH), and linkage analysis using a newly identified polymorphism.

PMID- 8978763
TI  - Tandem 1;30 translocation: a new structural abnormality in the horse (Equus
      caballus).
AB  - A 1;30 tandem translocation was found in an 8-yr-old thoroughbred stallion
      referred because of reduced fertility. The diagnosis was confirmed by GTG and CBG
      staining. This is the first report of a tandem translocation in the horse.

PMID- 8978764
TI  - Colcemid increases the frequency of chromosome abnormalities in human sperm.
AB  - The effect of Colcemid on the frequency and type of chromosomal abnormalities in
      human sperm was investigated. Using the human sperm and zona-free hamster egg
      fusion technique, penetrated eggs were cultured in the presence or absence of
      Colcemid. We used two different times of Colcemid treatment: standard Colcemid
      treatment (Colcemid-5 h) or long Colcemid treatment (Colcemid-17 h). Each
      Colcemid series had its own control series without Colcemid, thus ensuring that
      Colcemid was the only significant variable. A total of 771 sperm karyotypes from
      one normal donor was analyzed: 286 in the Colcemid-5 h series, 262 in the
      Colcemid-17 h series, and 223 in the two control series. In both Colcemid series
      there was a significant increase in the frequencies of hypohaploidy vs.
      hyperhaploidy (9.4% and 7.3% vs. 2.4% and 1.1%, for the Colcemid-5 h and Colcemid
      17 h series, respectively), in contrast to those obtained in the control series,
      in which the frequencies of hypohaploidy and hyperhaploidy were close to the 1:1
      relationship (4.9% vs. 4.0%) expected from nondisjunction. There was a
      significant increase in the frequency of structural abnormalities in both
      Colcemid series (16.1% and 14.5% for the Colcemid-5 h and Colcemid-17 h series,
      respectively) compared to the control series (6.3%). These results suggest that
      Colcemid significantly increases the frequency of hypohaploidy and unstable
      structural aberrations in human sperm.

PMID- 8978765
TI  - Translocation, t(17;22)(q22;q13), in dermatofibrosarcoma protuberans: a new tumor
      associated chromosome rearrangement.
AB  - A translocation, t(17;22)(q22;q13), was identified in two cases of
      dermatofibrosarcoma protuberans (DP). They bring to four the number of DP cases
      characterized by an identical t(17;22)(q22;q13), which can be considered as a new
      tumor-associated chromosome rearrangement. To date, this translocation has been
      found only in DP and its juvenile form, giant-cell fibroblastoma. This finding
      has two major consequences. First, it casts light on the development and
      significance in DP of ring chromosomes which consistently harbor sequences
      derived from chromosomes 17 and 22. Second, the identification of this new
      chromosome marker, and eventually of the underlying molecular rearrangement,
      should help to classify DP, a soft-tissue tumor of still uncertain cell origin.
      In addition, it could be used to differentiate DP from truly benign or malignant
      entities, in order that this tumor of intermediate malignancy could be adequately
      managed.

PMID- 8978766
TI  - The human HCLS1 gene maps to chromosome 3q13 by fluorescence in situ
      hybridization.
AB  - The human HS1 gene (HCLS1, hematopoietic cell-specific Lyn substrate 1) expressed
      in human hematopoietic cells encodes a major substrate of protein-tyrosine
      kinase, p75HS1. This intracellular protein is involved in the signal transduction
      pathways that initiate at the antigen receptors of both B and T lymphocytes.
      Fluorescence in situ hybridization using a 2.0-kb cDNA and an 8.0-kb genomic DNA
      clone of HCLS1 as probes revealed that the gene maps to 3q13.

PMID- 8978767
TI  - Assignment of the human beta-microseminoprotein gene (MSMB) to chromosome
      10q11.2.
AB  - Beta-microseminoprotein (MSP) is one of the major proteins secreted by the
      prostate, and its biological role in tumorigenesis of the prostate has been
      postulated. We assigned the human MSP gene (MSMB) to 10q11.2 with fluorescence in
      situ hybridization using a phage clone that has an MSP gene insert. Our mapping
      data shows that the gene is outside the previously identified LOH-regions (10p
      and 10q24-->qter) in prostate cancer cells and indicates that MSMB can be ruled
      out as a candidate for a tumor suppressor gene localized to those regions.

PMID- 8978768
TI  - Mapping of the metalloproteinase gene matrilysin (MMP7) to human chromosome 11q21
      ->q22.
AB  - The matrix metalloproteinase, matrilysin, is thought to play an important role in
      the early steps of tumor progression. We determined the chromosome location of
      the matrilysin gene (MMP7) by Southern and PCR analysis of two different panels
      of somatic cell hybrids and in situ hybridization of metaphase chromosomes.
      Matrilysin maps to the region, 11q21-->q22, adding MMP7 to the cluster of matrix
      metalloproteinase genes that have already mapped to this region.

PMID- 8978769
TI  - Deletion of the SRY region on the Y chromosome detected in bovine gonadal
      hypoplasia (XY female) by PCR.
AB  - In 6 sterile heifers which were female in appearance and in genital organs, all
      tissues derived from blood, skin, spleen and kidney had a single 60,XY type of
      metaphase plate. Although the SRY gene was detected by PCR in normal bull, it was
      not detected in normal cow or in 3 60,XY cases studied.

PMID- 8978770
TI  - Assignment of connexin 26 (GJB2) and 46 (GJA3) genes to human chromosome 13q11-
      >q12 and mouse chromosome 14D1-E1 by in situ hybridization.

PMID- 8978771
TI  - Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to
      human chromosome band 7q36.1.

PMID- 8978772
TI  - Reassignment of MYCL1 to human chromosome 1p34.3 by fluorescence in situ
      hybridization.
AB  - MYCL1 has been previously mapped to 1p32. This position was in contradiction with
      our mapping data of 1p deletions in neuroblastoma cell lines. Using FISH on high
      resolution R-banded chromosomes with a YAC clone for MYCL1 we were able to
      reassign the gene to subband 1p34.3. This new map position is of importance for
      the establishment of an integrated map for chromosome 1 and the search for
      disease genes in this region.

PMID- 8978773
TI  - Cloning and mapping of a human novel cDNA (NHP2L1) that encodes a protein highly
      homologous to yeast nuclear protein NHP2.
AB  - We have isolated a novel human cDNA that encodes a protein highly homologous to
      NHP2, a nuclear protein of yeast, that is thought to have an essential
      physiological function for cell viability. The 1,493-bp cDNA sequence includes an
      open reading frame of 384 bp. This gene (NHP2L1) was expressed in all human
      tissues examined, and was localized to chromosome hand 12q24.3 by fluorescence in
      situ hybridization.

PMID- 8978774
TI  - Correction of the spontaneous and DEB-induced chromosomal aberrations in Fanconi
      anemia cells of the FA(C) complementation group by the FACC gene.
AB  - Fanconi anemia (FA) cells are hypersensitive to the cytotoxic and clastogenic
      effects of DNA cross-linking agents. Four complementation groups have been
      identified to date. The gene (FACC) that corrects the hypersensitivity of one of
      them, FA(C), has been cloned. In the present study, both the increased
      spontaneous and diepoxybutane (DEB)-induced chromosomal instability in FA(C)
      lymphoblastoid cells were corrected by transfection of FACC.

PMID- 8978775
TI  - Close linkage between RNR and GPD genes on the tammar wallaby (Macropus eugenii)
      X chromosome.
AB  - No recombination was detected between two X-linked loci, RNR (Xp) and GPD (Xq),
      among 69 backcross progeny of two distantly related tammar wallaby (Macropus
      eugenii) subspecies. RNR loci are not dosage compensated, whereas the GPD locus
      is subject to the paternal X chromosome inactivation system that characterises
      female marsupials. The border of the region controlled by the marsupial X
      chromosome inactivation system has therefore been shown to lie between RNR and
      GPD.

PMID- 8978776
TI  - Metaphase and interphase mapping by FISH: improvement of chromosome banding and
      signal resolution in interphase nuclei by means of iterative deconvolution.
AB  - FISH images obtained with conventional epifluorescence microscopes are always
      blurred by glare and out of focus light emissions. In order to restore high
      contrast images, a procedure based on a modelling of the optical system in the
      microscope was developed and used for the processing of images acquired with a
      cooled CCD camera mounted on a fluorescence microscope. This procedure was tested
      on images of both mouse and human chromosomes stained with DAP1 and on images of
      interphase nuclei hybridized with pairs of cosmid probes. This method improves
      the definition and the sharpness of the DAPI G-banding and thus facilitates and
      speeds up the identification of chromosomes. When performed on images of
      interphase cell nuclei, this procedure allows the discrimination of fluorescent
      signals which appear partially overlapping on raw images. This significant
      improvement of spatial resolution is of particular interest for ordering sets of
      probes on DNA fibers.

PMID- 8978777
TI  - Regional mapping of the human platelet-activating factor receptor gene (PTAFR) to
      1p35-->p34.3 by fluorescence in situ hybridization.
AB  - The human platelet-activating factor cell-surface receptor (PTAFR) is a G protein
      coupled receptor thought to contribute to many atopic and inflammatory diseases
      and, perhaps, to the growth of some neoplasms. Exploring the possibility that the
      PTAFR might be involved in the genetic predisposition to any disease requires
      knowledge of its chromosomal localization. In this paper we have used a 20-kb
      human genomic fragment containing the coding sequence of the cloned PTAFR to
      determine the regional chromosomal localization of the gene. Using fluorescence
      in situ hybridization, the localization of the human PTAFR gene was mapped to
      1p35-->p34.3.

PMID- 8978779
TI  - Synteny conservation between parts of human chromosome 4q and bovine and ovine
      chromosomes 6.
AB  - Booroola Merino sheep are characterized by a high ovulation rate attributable to
      the presence of the FecB allele of the FEC gene. This gene, which has been
      assigned to sheep chromosome 6, is linked to the gene for EGF, which in man is
      located on the long arm of chromosome 4 (HSA 4q). To increase the number of known
      markers on sheep chromosome 6, we used comparative mapping data from sheep, man,
      and cattle. In our study, we show a synteny between EGF and the genes PDHA2 and
      FGF5 (from HSA 4q) and microsatellites ILSTS018, ILSTS090, and ILSTS093 (from
      bovine chromosome 6) in sheep. We also show that the conservation between HSA 4q
      and sheep chromosome 6 is disrupted between EGF and FGF2.

PMID- 8978778
TI  - Cloning, expression, and mapping of CKAPI, which encodes a putative cytoskeleton
      associated protein containing a CAP-GLY domain.
AB  - From a human fetal-brain cDNA library we isolated a novel cDNA clone encoding a
      protein containing a CAP-GLY domain that is highly conserved among several
      cytoskeleton-associated proteins. The CAP-GLY domain is thought to be essential
      for their association with microtubules. The cDNA, designated CKAPI (for
      cytoskeleton-associated protein I, glycine motif) contained an open reading frame
      of 579 nucleotides encoding 193 amino acids. Northern-blot analysis revealed
      expression of three transcripts, 1.0, 3.4, and 4.6 kb in size, in all tissues
      examined. The 1.0-kb transcript was significantly higher in brain and heart than
      in other tissues. This gene was mapped by FISH to chromosome bands 19q13.11-
      >q13.12.

PMID- 8978780
TI  - A complex satellite DNA polymorphism flanking the human ryanodine receptor gene
      (RYR1).
AB  - We describe a new highly polymorphic DNA marker flanking the human ryanodine
      receptor gene (RYR1) at chromosome band 19q13.1. The marker is composed of a 25bp
      minisatellite sequence, a compound microsatellite (AC)(AT), and an oligo-T
      stretch. STS mapping of previously published markers from 19q13.1 helped to
      integrate the genetic and physical maps of this region. Together with D19S422,
      the new polymorphism forms a pair of markers closely flanking either side of the
      RYR1 gene which may be useful for linkage studies in families susceptible to
      malignant hyperthermia and central core disease.

PMID- 8978781
TI  - Assignment of the human GATA4 gene to 8p23.1-->p22 using fluorescence in situ
      hybridization analysis.
AB  - Using fluorescence in situ hybridization, the human GATA4 gene, a member of the
      zinc-finger protein family recognizing the consensus GATA motif, was mapped to
      8p23.1-->p22. This result, in conjunction with gene mapping data on other GATA
      DNA binding proteins, suggests that genes encoding GATA-DNA binding proteins are
      dispersed throughout the genome, rather than clustered within a single locus.

PMID- 8978782
TI  - Effects of 5-azacytidine on the centromeric region of human fibroblasts studied
      by CREST staining and in situ hybridization on cytokinesis-blocked cells.
AB  - Several interphase methodologies have been applied in this study to investigate
      whether chemically induced undercondensation of the pericentromeric region of
      human fibroblast chromosomes promotes structural or numerical aberrations at the
      cell cycles following treatment. To achieve this aim, the effects of the
      hypomethylating agent 5-azacytidine (5- azaC) were studied on cytokinesis-blocked
      binucleated fibroblasts. This approach allowed the distribution of whole
      chromosomes or chromosome fragments in the daughter nuclei and micronuclei of
      treated cells to be followed, since the daughter nuclei of a single mitosis are
      maintained in one cytoplasm by treatment with the actin inhibitor cytochalasin B.
      Antikinetochore staining and in situ hybridization with an alpha-satellite probe
      capable of detecting all human centromeres on 5-azaC-induced micronuclei in
      binucleated fibroblasts indicated that the predominant effect of the chemical is
      to induce micronuclei lacking centromeres, suggestive of induced chromosome
      aberrations. Double in situ hybridization with alphoid and classical satellite
      DNA probes specific for chromosome 1 on binucleated fibroblasts was used to
      discriminate induced aneuploidy from breakage effects in the target area of
      hybridization. The results showed that undercondensation of the pericentromeric
      heterochromatin of human fibroblast chromosomes by treatment with 5-azaC produces
      structural chromosome aberrations involving the classical satellite DNA, whereas
      there was no evidence that the chemical induced chromosomal aneuploidy.

PMID- 8978783
TI  - Ordering of polymorphic markers in the chromosome region 3p21.
AB  - Starting from five markers, with a well-defined order from distal to proximal
      3p21, nine other markers could be inserted in this 3p21 map. Five were precisely
      mapped genetically. The other markers were ordered by FISH and/or deletion hybrid
      mapping. The overall 3p21 order from distal to proximal is as follows: D3S1298
      D3S1260-(D3S966, D3S1448 (= D3S1449)-D3S1029-D3S32-D3S643-D3F15S2 -D3S2968
      D3S1235-D3S1289-D3S1447-D3S1295.

PMID- 8978784
TI  - The ETV6, CDKN1B and D12S178 loci are involved in a segment commonly deleted in
      various 12p aberration in different hematological malignancies.
AB  - Structural rearrangements including deletions of the short arm of chromosome 12
      are frequent cytogenetic findings in various hematologic malignant disorders.
      Using FISH with a panel of DNA probes we detected loss of a common region of 12p
      in 22 patients with different hematologic disorders. Nine of them were
      characterized cytogenetically by a del(12p), seven by unbalanced translocations,
      and in the remaining cases the loss of the 12p region was masked by
      translocations and insertions, adding extra material to the short arm of
      chromosome 12. The smallest commonly deleted region found in all cases analyzed
      included ETV6, the gene for p27kipl (CDKN1B), and the D12S178 marker.

PMID- 8978785
TI  - Calcineurin A alpha (PPP3CA), calcineurin A beta (PPP3CB) and calcineurin B
      (PPP3R1) are located on human chromosomes 4, 10q21-->q22 and 2p16-->p15
      respectively.
AB  - Calcineurin (also called protein phosphatase-2B) is a calmodulin-regulated
      protein phosphatase which plays an important role in signal transduction. The
      enzyme is a heterodimer of a 58-59 kDa calmodulin-binding catalytic subunit
      (calcineurin A) and a small (i.e. 19 kDa) Ca(2+)-binding regulatory subunit
      (calcineurin B). The highly conserved calcineurin B is encoded by a single gene
      in all tissues except testes, whereas there are three isoforms of calcineurin A
      (alpha, beta and gamma) encoded by genes on three different chromosomes. This
      enzyme can play a critical role in transcriptional regulation and growth control
      in T lymphocytes by a mechanism believed to involve dephosphorylation of the
      nuclear factor NF-AT which is essential for transcription of the interleukin-2
      gene. To better evaluate the potential role of the calcineurin genes in human
      genetic disorders, we have studied their chromosome locations. Calcineurin B
      (PPP3R1) is located on human chromosome 2p16-->p15 and calcineurin A beta
      (PPP3CB, previous gene symbol CALNB) is present on 10q21-->q22. We confirm the
      localization of calcineurin A alpha (PPP3CA, previous gene symbol CALNA) to
      chromosome 4 without regional localization.

PMID- 8978786
TI  - Cloning, expression and chromosomal mapping of a novel cyclophilin-related gene
      (PPIL1) from human fetal brain.
AB  - We isolated a human cDNA clone encoding a novel protein homologous to
      cyclophilins, specific cellular targets of cyclosporin A, which are conserved in
      species ranging from human to prokaryotes. This cDNA, designated hCyPX, contained
      an open reading frame of 498 nucleotides encoding 166 amino acids. Computer
      analysis indicated that its predicted amino acid sequence had 41.6%, 40.4%, and
      39.2% homology to those of human, bovine, and Drosophila cyclophilins,
      respectively. Northern blot analysis indicated ubiquitous expression in adult
      human tissues, but most abundant expression in heart. Fluorescence in situ
      hybridization to human metaphase chromosomes localized this gene (PPIL1,
      peptidylprolyl isomerase [cyclophilin]-like 1) to chromosome bands 2p23.3-
      >p23.1.

PMID- 8978787
TI  - SOX20, a new member of the SOX gene family, is located on chromosome 17p13.
AB  - SOX genes share a high sequence identity with the HMG box present in the testis
      determining gene SRY. We have identified a HMG box-like sequence motif on six
      contiguous cosmids, which cross-hybridize to a SOX9 cDNA probe. A data base
      search revealed a high similarity of the deduced amino acid sequence to the human
      SOX12 and the murine Sox16 HMG domains. The cosmids were assigned to chromosome
      17p13 by FISH analysis.

PMID- 8978789
TI  - Assignment of the human gene (GLCLR) that encodes the regulatory subunit of gamma
      glutamylcysteine synthetase to chromosome 1p21.
AB  - We recently assigned the human gene (GLCLC) that encodes the catalytic subunit of
      gamma-glutamylcysteine synthetase (glutamate-cysteine ligase, E.C. 6.3.2.2) to
      human chromosome 6p12. Here we specify the chromosomal sublocalization of the
      human gene (GLCLR) that encodes the regulatory subunit of E.C. 6.3.2.2 to
      chromosome 1p21.

PMID- 8978788
TI  - Assignment of the human myogenic factors 5 and 6 (MYF5, MYF6) gene cluster to
      12q21 by in situ hybridization and physical mapping of the locus between D12S350
      and D12S106.

PMID- 8978790
TI  - [Allogeneic peripheral blood stem cell transplantation].
AB  - Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has been
      increasingly used as an alternative to allogeneic bone marrow transplantation
      (allo-BMT). In comparison with allo-BMT, preliminary results indicate that rapid
      hematopoietic engraftment can be obtained, and there is no increase in the
      incidence and severity of acute GVHD after allo-PBSCT. Furthermore, general
      anesthesia is not required to collect a sufficient number of PBSCT, which are
      usually mobilized by G-CSF administration. Therefore, allo-BMT will be replaced
      by allo-PBSCT in near future.

PMID- 8978791
TI  - [CMF or CAF combination chemotherapy for breast cancer].
AB  - Cyclophosphamide is one of the alkylating agents and is a masked from compound.
      Combination chemotherapy with CMF or CAF has been commonly used as a first-line
      chemotherapy for recurrent and advanced breast cancer. The clinical efficacy of
      CMF chemotherapy (CPA + MTX + 5-FU) was evaluated on advanced and recurrent
      breast cancer. It is considered to be one of the most useful treatments. CAF
      chemotherapy (CPA + ADM + 5-FU) is also thought to be effective against breast
      cancers.

PMID- 8978792
TI  - [Effective clinical use of cyclophosphamide in hematological malignancies].
AB  - Cyclophosphamide (CPA) is the most widely used alkylating agent in the treatment
      of hematological malignancies. We review current clinical potential of high-dose
      CPA administration in this field. The efficacy of dose intensification of CPA in
      CHOP regimen for patients with aggressive lymphoma is being investigated in some
      clinical trials. High-dose CPA administration and G-CSF infusion effectively
      mobilize high levels of peripheral blood stem cell suitable for autografting.
      High-dose regimens of CPA alone or in combination with other agents also have
      been used to treat various hematological malignancies in conjunction with stem
      cell transplantation (SCT). A variety of adverse effects have been observed with
      the high-dose CPA used in preparative regimens for SCT. Hemorrhagic cystitis and
      cardiac toxicity are common and dose-limiting toxic effect of high-dose CPA
      administration.

PMID- 8978793
TI  - [Methotrexate in gynecologic oncology].
AB  - Methotrexate produced the first remission in leukemia and the first cure of a
      solid tumor, choriocarcinoma. Methotrexate tightly binds to dihydrofolate
      reductase (DHFR), blocking the reduction of dihydrofolate to tetrahydrofolic
      acid, the active form of folic acid. Methotrexate also directly inhibits the
      folate-dependent enzymes of de novo purine and thymidylate synthesis. Resistance
      to methotrexate may develop as a result of elevated DHFR activity or defective
      transport of methotrexate into malignant cells. Increased DHFR enzyme levels may
      also result from amplification of the DHFR gene, which is now clinically
      significant in selected patients. Methotrexate is an active drug in the first
      line treatment of gestational trophoblastic disease (GTD) and in metastatic
      squamous cell carcinoma of the cervix. Since the introduction of methotrexate
      chemotherapy for malignant GTD, most hospitals have reported almost 100% cure
      rates for patients with nonmetastatic disease using single-agent regimens.
      Patients with low-risk metastatic disease have been treated with methotrexate and
      folinic acid and over 50% complete remission rates have been reported. Patients
      with metastatic GTD who had one or more high-risk factors benefited from initial
      multiagent chemotherapy, rather than waiting for acquisition of drug-resistance
      to single-agent therapy to start multiagent treatment. Using multiagent
      combination chemotherapy such as MAC (methotrexate, actinomycin D,
      cyclophosphamide) or EMA-CO (etoposide, methotrexate, actinomycin D and
      cyclophosphamide, vincristine), most investigators have reported remission in
      approximately 60 to 80% of patients with high-risk metastatic GTD. Although the
      role of chemotherapy in carcinoma of the cervix has been limited for several
      reasons, trial of combination chemotherapy including methotrexate has been
      reported. However, it is still impossible to draw definite conclusions as to
      whether methotrexate combined with another clearly active drug may yield a
      superior response rate and survival.

PMID- 8978794
TI  - [Methotrexate-leucovorin rescue therapy: pharmacological characteristics and
      clinical effective use].
AB  - An antifolate first introduced into the clinic about half decades ago,
      Methotrexate is effective against a variety of human cancers, when administered
      alone or in combination with leucovorin rescue at wide-ranging doses and by many
      different schedules. We know much more about MTX and its molecular and cellular
      pharmacology and mechanisms of anti-cancer action in light of current knowledge
      of the biochemistry of folate. This understanding has stimulated novel approaches
      to the clinical application of the drug and has greatly enhanced its therapeutic
      efficacy.

PMID- 8978795
TI  - [Sequential methotrexate and 5-fluorouracil].
AB  - There are two purported biochemical mechanisms to explain the sequence-dependent
      synergy between methotrexate (MTX) and 5-fluorouracil (5-FU). One hypothesis is
      to increase incorporation of FU-TP into RNA and another is more sustained
      inhibition of DNA synthesis. Clinical studies on MTX.5-FU, significantly higher
      response rates and longer survival have been reported in gastric and colorectal
      cancer, especially high dose MTX.5-FU and adriamycin (FAMTX) in gastric cancer.
      An optimal schedule for treatment has not yet been found. Reviewing data from the
      literature, a one-3 hour interval between the two drugs in gastric cancer and 3-8
      hours in colorectal cancer seems to obtain better results. Sequential MTX.5-FU
      seems to be a very promising combination.

PMID- 8978796
TI  - [Adriamycin--breast cancer].
AB  - The significance of doxorubicin (ADR) was reviewed in the treatment of advanced
      as well as early breast cancer. The history of ADR treatment, mainly as a
      combination of CAF, or FAC, has revealed that ADR is still the key drug for
      breast cancer, the response rate being 40-60%. A multivariate analysis in 182
      advanced breast cancer cases showed that the predictive factor was the dominant
      site of metastasis, and performance status (PS). Overall survival was determined
      with the age, the dominant site of metastasis, and PS. Recently the combination
      chemotherapy including ADR was evaluated to be equivalent to CMF type
      chemotherapy in the adjuvant settings.

PMID- 8978797
TI  - [Characteristic and effective usage of adriamycin].
AB  - The utility of adriamycin (doxorubicin), an anti-cancer antibiotic, for the
      treatment of transitional cell carcinoma of the bladder has been appreciated.
      Adriamycin is still used intravesically for superficial bladder cancer to avoid
      implantation of floating cancer cells after transurethral resection, to decrease
      the incidence of recurrence and treat an unresected part of the tumor. On the
      other hand, cisplatin-based multi-drug chemotherapies including adriamycin have
      proven effective in treating locally and systemically advanced bladder cancer.

PMID- 8978798
TI  - [Etoposide in the treatment of small-cell lung cancer].
AB  - Etoposide is one of the most active agents for small-cell lung cancer. It is
      usually administered intravenously over 3 to 5 consecutive days in combination
      with cisplatin, carboplatin, cyclophosphamide, or adriamycin. Recently, chronic
      daily administration of low dose oral etoposide and very high dose intravenous
      administration with autologous blood stem cell transplantation have been tried to
      improve treatment outcome. However, the standard dose, schedule, or route of
      etoposide administration have not been established. In this paper, the clinical
      efficacy and adverse effects of etoposide in the treatment of small-cell lung
      cancer are reviewed.

PMID- 8978799
TI  - [Etoposide (VP-16) in gynecologic malignancy].
AB  - Clinical application of etoposide (VP-16) for gynecologic malignancy has been
      investigated in trophoblastic disease, ovarian, endometrial and cervical cancer.
      Etoposide has proved to be one of the most effective agents for trophoblastic
      disease. It is widely used in single or multiple drug regimens in chemotherapy of
      the disease. Furthermore, this drug is observed to be active in the combination
      of BLM with CDDP for germ cell tumor of the ovary. It is now playing an important
      role in chemotherapy of this tumor.

PMID- 8978800
TI  - [The role of etoposide therapy in urogenital cancer].
AB  - Testicular cancer is recognized as a model of curable cancer by chemotherapy, and
      etoposide is the one of the most important drugs in its treatment. Etoposide has
      been used with cisplatin and bleomycin as a first-line combination chemotherapy
      since the early 1980s. It is now the key drug in the setting of high-dose
      chemotherapy for refractory cases. Oral, low-dose etoposide may provide effective
      palliation in some patients refractory to possible curative salvage therapy. Oral
      etoposide may also play a role in the maintenance therapy adjunctive to salvage
      therapy. Nevertheless, etoposide has failed to show definite therapeutic efficacy
      in the treatment of renal cell carcinoma and bladder cancer. The combination
      therapy of oral etoposide and estramustine, however, showed promising results for
      the treatment of hormone-refractory prostate cancer. Further investigations are
      required for this new treatment strategy for prostatic cancer.

PMID- 8978801
TI  - [Etoposide 21 therapy for malignant lymphoma].
AB  - Oral administration of etoposide 50 mg daily for 21 days was studied in 83
      patients with malignant lymphoma who were not indicated for intensive treatment.
      Dose escalation to 75 mg was allowed for previously untreated cases and those
      with body surface over 1.5 m2. The majority of patients were: median age 69,
      outpatient, previously treated, with clinical stage III, IV. Overall response
      rate was 52.5%, including 10 CR. Response rates for each background factor were:
      age > or = 65, 63.8%* < 65, 36.4%, PS 0, 56.5%, 1, 53.9%, 2 approximately 3,
      25.0%, outpatient 65.9%, inpatient 24.0%. Clinical stage I, II, 57.1%; III, IV,
      50.0%. Dosage 50 mg 49.3%; 75 mg 85.7%. Previously untreated, 81.8%; pretreated,
      47.8%*(*p < 0.05). TOXICITY: moderate side effects such as loss of appetite,
      nausea and leukocytopenia were observed. Those were tolerable and recovery was
      achieved by reduction of dose or discontinuation. Intensive treatment is the most
      popular therapy for malignant lymphoma, however, there are certain patients not
      indicated for such intensive treatment. For such patients this etoposide 21
      therapy can offer a new way of palliative therapy to allow them to remain at home
      while maintaining a high quality of life.

PMID- 8978802
TI  - [Bropirimine (U-54461S) phase I clinical studies].
AB  - Bropirimine (U-54461S), an oral interferon (IFN) inducer that has also a direct
      antiproliferative activity, is a novel antitumor agent. To investigate the safety
      and pharmacokinetics of bropirimine tablets and to measure IFN concentrations in
      patients with cancer, Phase I studies were conducted. In single dose study (0.25
      to 3g) and multiple-dose study with one-day dosing (1 or 2g, every one or two
      hours, three times a day), bropirimine treatment was well tolerated by the
      patients with cancer. In multiple-dose study with consecutive days dosing (1 or
      2g, every 2 hours, three times a day for 3 or 5 consecutive days), a regimen with
      a dose of 1g orally administered every two hours, three times a day for three
      consecutive days was considered to be tolerable to cancer patients. Adverse drug
      reactions frequently observed were generalized malaise, fever, nausea/vomiting,
      anorexia, headache/dull headache, and tachycardia. Abnormalities in laboratory
      tests frequently observed were leukemia, neutropenia, thrombocytopenia, and
      elevation in GOT/GPT. IFN was not induced in any patients in the single dose
      study. It was, however, induced in 3 of 16 cases (18.8%) in the one-day dosing
      study and in 6 of 7 cases (85.7%) in the consecutive days dosing study. As to
      clinical antitumor efficacy, a decrease in size of the tumor lesions and
      improvement in subjective/objective symptoms were noted in two cases in the one
      day dosing study. With these findings, the regimen with the dose of 1g orally
      administered every two hours, three times a day for three consecutive days with a
      four-day drug-free interval per week was recommended for early phase II studies.

PMID- 8978803
TI  - [Chemotherapy for peritoneal dissemination in gastric cancer under ureteral
      catheterization].
AB  - The treatment of peritoneal dissemination of gastric cancer is mainly
      chemotherapy, but it use is often limited by ileus, hydronephrosis and jaundice.
      We employed a ureteral catheter for 6 patients with hydronephrosis due to
      peritoneal dissemination. Chemotherapy (CDDP + ADM + 5-FU or MTX + 5-FU) was
      administered in 5 patients. After ureteral catheterization, renal function was
      kept within normal ranges, so chemotherapy was performed safely. One of five
      patients became CR and the effect of the treatment was satisfactory (PR: 1, NC:
      2). Thus, chemotherapy after ureteral catheterization may be effective for
      patients with peritoneal dissemination and hydronephrosis.

PMID- 8978804
TI  - [Significance of 5'-deoxy-5-fluorouridine (5'-DFUR) administration before surgery
      for advanced gastric and colonic cancers--activity of pyrimidine nucleoside
      phosphorylase (PyNPase) and serum immunosuppressive acidic protein (IAP)].
AB  - We administered preoperatively 5'-deoxy-5-fluorouridine (5'-DFUR) for treatment
      of advanced gastric and colonic cancers, and measured pyrimidine nucleoside
      phosphorylase (PyNPase) in the excised tumor sample and serum immunosuppressive
      acidic protein (serum IAP), which is an index of the immunity of host-bearing
      cancer, while studying its direct antitumor effect and improved immunity.
      Patients with 24 advanced gastric cancers and 36 colonic cancers were randomly
      divided into a preoperatively administered group and a non-administered group. In
      the preoperatively administered group, 5'-DFUR (1,200 mg/day) was orally
      administered on preoperative days 7 approximately 14. After collecting samples
      (about 0.5 g) from adjacent normal tissues with tumor within 30 minutes after
      extirpation of tumor and freezing those less than -20 degrees C, the PyNPase
      level was measured as soon as possible. Moreever, serum IAP levels at pre
      administration in the administered group and on admission in the non-administered
      group were measured. Those in the administered group were measured again on the
      operative day. No decreasing tendency of PyNPase was generally found in cases
      with gastric colonic cancers, and no significant difference in stage-II was not
      either. However, a decreasing tendency in tumor activity was found by pre
      administration. Moreover, there was significant improvement in the serum IAP
      level in cases with gastric and colonic cancers by pre-operative administration
      of 5'-DFUR. This tendency was also found in advanced colonic cancer with Dukes-C
      by Dukes's classification. In conclusion, it was suggested that the pre-operative
      administration of 5'-DFUR for treatment of advanced gastric and colonic cancers
      has a favorable influence for prognosis because the tumor region was retarded by
      the high PyNPase activity according to the severity of tumors and elevating
      tendency of the immune response in host.

PMID- 8978805
TI  - [Administration of oral etoposide for one year as adjuvant chemotherapy for non
      small cell lung cancer-side effect].
AB  - The possibility of using etoposide 25 mg daily as adjuvant chemotherapy for non
      small cell lung cancer was discussed. Initially, 73 patients who had undergone
      resection participated in this trial; 49 of them were eligible, 24 including a
      patient over 70 years of age (8) took the drug for 1 year, 22 patients resigned
      from the study due to side effects, and a further 3 patients died during the
      trial. The main side effects observed were gastro-intestinal trouble (13) and
      pneumonia (4). The side effects of this drug appeared early in the treatment
      phase. During the first month of treatment, 9 patients discontinued the drug due
      to side effects, and 10 more did so within 4 months. To achieve optimal
      conditions for the trial study of low-dose etoposide it was found important to
      select patients under 70 years of age and to control side effects of the drug on
      the gastro-intestinal tract from the beginning.

PMID- 8978806
TI  - [Effect of FUT-187, oral serine protease inhibitor, on inflammation in the
      gastric remnant].
AB  - Excessive enterogastric reflux following partial gastrectomy is believed to be
      responsible for the cause of inflammation in the gastric remnant. We examined the
      effect of FUT-187, a synthetic serine protease inhibitor, on symptoms and
      endoscopic findings in 33 patients who were diagnosed endoscopically as
      postgastrectomy gastritis. Patients took 50 mg FUT-187 orally after each meal and
      at bedtime for 8 weeks. Before treatment, 30 patients (91%) suffered from several
      symptoms including regurgitation and/or bitter taste in the mouth (49%),
      epigastric pain (42%) and nausea (36%). From endoscopic observation, erythema was
      detected in 32 patients, edema in 23 patients and erosion and/or ulcer in 9
      patients. After treatment the global improvement rating for subjective symptoms
      was 76.7% (23/30) and the improvement of endoscopic findings was 63.6% (21/33).
      Diarrhea was observed in one patient but could be easily controlled by
      discontinuation of the drug. Our results suggest that FUT-187 can be a useful
      drug for the treatment of postgastrectomy gastritis with its efficacy and safety.

PMID- 8978807
TI  - [Three cases of resected primary mediastinal yolk sac tumor following six courses
      of bleomycin, etoposide and cisplatin (BEP) combination chemotherapy].
AB  - We experienced three cases of primary mediastinal yolk sac tumor which were
      resected after 6 courses of BEP chemotherapy with G-CSF support. All cases had
      high levels of AFP. CT scan revealed an anterior mediastinal tumor infiltrating
      the surrounding tissue in all cases, and multiple pulmonary nodules in one case.
      The serum AFP level decreased markedly, but did not return to normal after the
      chemotherapy was completed. The markedly decreased mediastinal tumor masses were
      removed with en-bloc resection of the lung and pericardium. Viable tumor cells
      were not present in the resected tumors. These three cases remain free of disease
      at present, 3 years, 9 months and 5 months after operation.

PMID- 8978808
TI  - [A case of recurrent squamous cell carcinoma of cervix successfully treated with
      BOMP].
AB  - Combination chemotherapy consisting of bleomycin, vincristine, mitomycin C and
      cisplatin (BOMP) was applied to a case (57 years old) with recurrence of squamous
      cell carcinoma of the cervix. The patient with FIGO stage IIIb cervical carcinoma
      had been treated with radiotherapy seven years ago. She was affected by malignant
      pericardial effusion, and was treated with direct intrapericardial administration
      of cisplatin (20 mg). After instillation, ultrasonography and computed tomography
      showed the wall thickening of colon and marked ascites. Barium enema showed the
      circumferential narrowing and serrations of colon, and it was diagnosed to be
      carcinomatous peritonitis. She was treated with BOMP consisting of BLM (5 mg,
      i.m., days 1 - 5), VCR (1 mg, i.v., day 5'), MMC (8 mg, i.v., day 5), and CDDP
      (70 mg, d.i.v., day 5). After three courses of BOMP therapy, she achieved a
      complete response with few toxic effects and did not require special care. She
      has been free of disease for six months and her performance status is 0. This
      encouraging result warrants the use of this combination chemotherapy regimen in
      other patients with recurrent squamous cell carcinoma of the cervix.

PMID- 8978810
TI  - [Antitumor effect of TNP-470 against tongue carcinoma model by intratumor
      administration].

PMID- 8978809
TI  - [Two cases of relapse or refractory germ cell tumor who had been treated with
      combination chemotherapy of cisplatin and carboplatin].
AB  - We tried a combination chemotherapy with cisplatin (CDDP) and carboplatin (CBDCA)
      (CDDP/CBDCA regimen) as salvage therapy for 2 cases with recurrent or refractory
      Germ Cell Tumor (GCT). Case 1 was a 29-year-old man with 2nd relapsed embryonal
      carcinoma and seminoma originating from testis. Case 2 was a 23-year-old man with
      primary refractory embryonal carcinoma and yolk sac tumor originating from
      mediastinum. CDDP and CBDCA were administered at the dose of 120 mg/m2 and 350
      mg/m2 on day 1, and vinblastin was administered at the dose of 10 mg/body on day
      2. In one of two cases, a complete response was obtained. Non-hematologic
      toxicity of CDDP/CBDCA regimen was tolerable. It is suggested that this
      combination chemotherapy is useful for GCT recurrence.

PMID- 8978811
TI  - [A study of combination chemotherapy using, 5-FU and CDDP in patients with
      advanced non-small cell lung cancer].

PMID- 8978812
TI  - [Antimetastatic effects of UFT on murine liver metastasis model using L5178YHM
      lymphoma].

PMID- 8978813
TI  - Three-dimensional reconstruction of painted human interphase chromosomes: active
      and inactive X chromosome territories have similar volumes but differ in shape
      and surface structure.
AB  - This study provides a three-dimensional (3D) analysis of differences between the
      3D morphology of active and inactive human X interphase chromosomes (Xa and Xi
      territories). Chromosome territories were painted in formaldehyde-fixed, three
      dimensionally intact human diploid female amniotic fluid cell nuclei (46, XX)
      with X-specific whole chromosome compositive probes. The colocalization of a 4,6
      diamidino-2-phenylindole dihydrochloride-stained Barr body with one of the two
      painted X territories allowed the unequivocal discrimination of the inactive X
      from its active counterpart. Light optical serial sections were obtained with a
      confocal laser scanning microscope. 3D-reconstructed Xa territories revealed a
      flatter shape and exhibited a larger and more irregular surface when compared to
      the apparently smoother surface and rounder shape of Xi territories. The
      relationship between territory surface and volume was quantified by the
      determination of a dimensionless roundness factor (RF). RF and surface area
      measurements showed a highly significant difference between Xa and Xi territories
      (P < 0.001) in contrast to volume differences (P > 0.1). For comparison with an
      autosome of similar DNA content, chromosome 7 territories were additionally
      painted. The 3D morphology of the chromosome 7 territories was similar to the Xa
      territory but differed strongly from the Xi territory with respect to RF and
      surface area (P < 0.001).

PMID- 8978814
TI  - Lamin proteolysis facilitates nuclear events during apoptosis.
AB  - Expression of the adenovirus E1A oncogene stimulates both cell proliferation and
      p53-dependent apoptosis in rodent cells. p53 implements apoptosis in all or in
      part through transcriptional activation of bax, the product of which promotes
      cell death. The adenovirus E1B 19K product is homologous in sequence and in
      function to Bcl-2, both of which bind to and inhibit the activity of Bax and
      thereby suppress apoptosis. The E1B 19K protein also interacts with the nuclear
      lamins, but the role of this interaction in the regulation of apoptosis is not
      known. Lamins are, however, substrates for members of the interleukin-1 beta
      converting enzyme (ICE) family of cysteine proteases that are activated during
      apoptosis and function downstream of Bcl-2 in the cell death pathway. lamins are
      degraded during E1A-induced p53-dependent apoptosis. Lamin A and C are cleaved
      into 47- and 37-kD fragments, respectively, and the site of proteolysis is mapped
      to a conserved aspartic acid residue at position 230. The cleavage of lamins
      during apoptosis is consistent with the activation of an ICE-related cysteine
      protease down-stream of p53. No lamin protease activity was detected in cells
      expressing the E1B 19K protein, indicating that 19K functions upstream of
      protease activation in inhibiting apoptosis. Substitution of the aspartic acid at
      the cleavage site produced a mutant lamin protein that was resistant to
      proteolysis both in vitro and in vivo. Expression of uncleavable mutant lamin A
      or B attenuated apoptosis, delaying cell death and the associated DNA
      fragmentation by 12 h. Mutant lamin expressing cells failed to show the signs of
      chromatin condensation and nuclear shrinkage typical of cell death by apoptosis.
      Instead, the nuclear envelope collapsed and the nuclear lamina remained intact.
      However, the late stage of apoptosis was morphologically unaltered and formation
      of apoptotic bodies was evident. Thus, lamin breakdown by proteolytic degradation
      facilitates the nuclear events of apoptosis perhaps by facilitating nuclear
      breakdown.

PMID- 8978815
TI  - A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase
      activating protein RanGAP1 between the cytosol and the nuclear pore complex.
AB  - Ran is a nuclear Ras-like GTPase that is required for the bidirectional transport
      of proteins and ribnucleoproteins across the nuclear pore complex (NPC). A key
      regulator of the Ran GTP/GDP cycle is the 70-kD Ran-GTPase-activating protein
      RanGAP1. Here, we report the identification and localization of a novel form of
      RanGAP1. Using peptide sequence analysis and specific mAbs, RanGAP1 was found to
      be modified by conjugation to a ubiquitin-like protein. Immunoblot analysis and
      immunolocalization by light and EM demonstrated that the 70-kD unmodified from of
      RanGAP1 is exclusively cytoplasmic, whereas the 90-kD modified form of RanGAP1 is
      associated with the cytoplasmic fibers of the NPC. The modified form of RanGAP1
      also appeared to associated with the mitotic spindle apparatus during mitosis.
      These findings have specific implications for Ran function and broad implications
      for protein regulation by ubiquitin-like modifications. Moreover, the variety and
      function of ubiquitin-like protein modifications in the cell may be more diverse
      than previously realized.

PMID- 8978816
TI  - Formation of nascent secretory vesicles from the trans-Golgi network of endocrine
      cells is inhibited by tyrosine kinase and phosphatase inhibitors.
AB  - Recent evidence suggests that secretory vesicle formation from the TGN is
      regulated by cytosolic signaling pathways involving small GTP-binding proteins,
      heterotrimeric G proteins, inositol phospholipid metabolism, and protein
      serine/threonine phosphorylation. At the cell surface, protein phosphorylation
      and dephosphorylation on tyrosine residues can rapidly modulate cytosolic
      signaling pathways in response to extracellular stimuli and have been implicated
      in the internalization and sorting of signaling receptors. to determine if
      phosphotyrosine metabolism might also regulate secretory vesicle budding from the
      TGN, we treated permeabilized rat pituitary GH3 cells with inhibitors of either
      tyrosine phosphatases or tyrosine kinases. We demonstrate that the tyrosine
      phosphatase inhibitors pervanadate and zinc potently inhibited budding of nascent
      secretory vesicles. Tyrphostin A25 (TA25) and other tyrosine kinase inhibitors
      also prevented secretory vesicle release, suggesting that vesicle formation
      requires both phosphatase and kinase activities. A stimulatory peptide derived
      from the NH2 terminus of the small GTP-binding protein ADP ribosylation factor 1
      (ARF1) antagonized the inhibitory effect of TA25, indicating that both agents
      influence the same pathway leading to secretory vesicle formation.
      Antiphosphotyrosine immunoblotting revealed that protein tyrosine phosphorylation
      was enhanced after treatment with tyrosine phosphatase or kinase inhibitors.
      Subcellular fractionation identified several tyrosine phosphorylated polypeptides
      of approximately 175, approximately 130, and 90-110 kD that were enriched in TGN
      containing Golgi fractions and tightly membrane associated. The phosphorylation
      of these polypeptides correlated with inhibition of vesicle budding. Our results
      suggest that in endocrine cells, protein tyrosine phosphrylation and
      dephosphorylation are required for secretory vesicle release from the TGN.

PMID- 8978817
TI  - A novel fluorescence-activated cell sorter-based screen for yeast endocytosis
      mutants identifies a yeast homologue of mammalian eps15.
AB  - A complete understanding of the molecular mechanisms of endocytosis requires the
      discovery and characterization of the protein machinery that mediates this aspect
      of membrane trafficking. A novel genetic screen was used to identify yeast
      mutants defective in internalization of bulk lipid. The fluorescent lipophilic
      styryl dye FM4-64 was used in conjunction with FACS to enrich for yeast mutants
      that exhibit internalization defects. Detailed characterization of two of these
      mutants, dim1-1 and dim2-1, revealed defects in the endocytic pathway. Like other
      yeast endocytosis mutants, the temperature-sensitive dim mutant were unable to
      endocytose FM4-64 or radiolabeled alpha-factor as efficiently as wild-type cells.
      In addition, double mutants with either dim1-delta or dim2-1 and the endocytosis
      mutants end4-1 or act1-1 displayed synthetic growth defects, indicating that the
      DIM gene products function in a common or parallel endocytic pathway.
      Complementation cloning of the DIM genes revealed identity of DIM1 to SHE4 and
      DIM2 to PAN1. Pan1p shares homology with the mammalian clathrin adaptor
      associated protein, eps15. Both proteins contain multiple EH (eps15 homology)
      domains, a motif proposed to mediate protein-protein interactions. Phalloidin
      labeling of filamentous actin revealed profound defects in the actin cytoskeleton
      in both dim mutants. EM analysis revealed that the dim mutants accumulate
      vesicles and tubulo-vesicular structures reminiscent of mammalian early
      endosomes. In addition, the accumulation of novel plasma membrane invaginations
      where endocytosis is likely to occur were visualized in the mutants by electron
      microscopy using cationized ferritin as a marker for the endocytic pathway. This
      new screening strategy demonstrates a role for She4p and Pan1p in endocytosis,
      and provides a new general method for the identification of additional
      endocytosis mutants.

PMID- 8978818
TI  - A role for N-myristoylation in protein targeting: NADH-cytochrome b5 reductase
      requires myristic acid for association with outer mitochondrial but not ER
      membranes.
AB  - N-myristoylation is a cotranslational modification involved in protein-protein
      interactions as well as in anchoring polypeptides to phospholipid bilayers;
      however, its role in targeting proteins to specific subcellular compartments has
      not been clearly defined. The mammalian myristoylated flavoenzyme NADH-cytochrome
      b5 reductase is integrated into ER and mitochondrial outer membranes via an
      anchor containing a stretch of 14 uncharged amino acids downstream to the NH2
      terminal myristoylate glycine. Since previous studies suggested that the
      anchoring function could be adequately carried out by the 14 uncharged residues,
      we investigated a possible role for myristic acid in reductase targeting. The
      wild type (wt) and a nonmyristoylatable reductase mutant (gly2-->ala) were stably
      expressed in MDCK cells, and their localization was investigated by
      immunofluorescence, immuno-EM, and cell fractionation. By all three techniques,
      the wt protein localized to ER and mitochondria, while the nonmyristoylated
      mutant was found only on ER membranes. Pulse-chase experiments indicated that
      this altered steady state distribution was due to the mutant's inability to
      target to mitochondria, and not to its enhanced instability in that location.
      Both wt and mutant reductase were resistant to Na2CO3 extraction and partitioned
      into the detergent phase after treatment of a membrane fraction with Triton X
      114, demonstrating that myristic acid is not required for tight anchoring of
      reductase to membranes. Our results indicate that myristoylated reductase
      localizes to ER and mitochondria by different mechanisms, and reveal a novel role
      for myristic acid in protein targeting.

PMID- 8978820
TI  - alpha-Tubulin limits its own synthesis: evidence for a mechanism involving
      translational repression.
AB  - A Chinese hamster alpha-tubulin cDNA was modified to encode an 11-amino acid
      carboxyl-terminal extension containing the immunodominant epitope from influenza
      hemagglutinin antigen (to create HA alpha 1-tubulin) and was cloned into a vector
      for expression in mammalian cells. 12 stable CHO cell lines expressing this HA
      alpha 1-tubulin were isolated and characterized. HA alpha 1-tubulin incorporated
      into all classes of microtubules, assembled to the same extent as the endogenous
      tubulin, and did not perturb the growth of the cells in which it was expressed.
      However, overexpression of HA alpha 1-tubulin strongly repressed the synthesis of
      endogenous alpha-tubulin while having little or no effect on the synthesis of
      beta-tubulin. Treatment of transfected cells with sodium butyrate to induce even
      greater expression of HA alpha 1-tubulin led to a further decrease in synthesis
      of endogenous alpha-tubulin that was fully reversible upon removal of the
      inducer. Decreased synthesis of alpha-tubulin in transfected cells did not result
      from decreased levels of alpha-tubulin mRNA, as demonstrated by ribonuclease
      protection assays. On the other hand, colchicine, a drug previously shown to
      destabilize the tubulin message, caused a clear reduction in both protein
      synthesis and mRNA levels for transfected HA alpha 1-tubulin and endogenous alpha
      tubulin, thus indicating that the decreased alpha-tubulin synthesis observed as a
      result of HA alpha 1-tubulin overexpression is distinct from the previously
      described autoregulation of tubulin. The results are consistent with a mechanism
      in which free alpha-tubulin inhibits the translation of its own message as a way
      of ensuring stoichiometric synthesis of alpha- and beta-tubulin.

PMID- 8978819
TI  - Exclusion of CD45 inhibits activity of p56lck associated with glycolipid-enriched
      membrane domains.
AB  - p56lck (Lck) is a lymphoid-specific Src family tyrosine kinase that is critical
      for T-cell development and activation. Lck is also a membrane protein, and
      approximately half of the membrane-associated Lck is associated with a glycolipid
      enriched membrane (GEM) fraction that is resistant to solubilization by Triton X
      100 (TX-100). To compare the membrane-associated Lck present in the GEM and TX
      100-soluble fractions of Jurkat cells, Lck from each fraction was immunoblotted
      with antibody to phosphotyrosine. Lck in the GEM fraction was found to be
      hyperphosphorylated on tyrosine, and this correlated with a lower kinase specific
      activity relative to the TX-100-soluble Lck. Peptide mapping and phosphatase
      diagests showed that the hyperphosphorylation and lower kinase activity of GEM
      associated Lck was due to phosphorylation of the regulatory COOH-terminal Tyr505.
      In addition, we determined that the membrane-bound tyrosine phosphatase CD45 was
      absent from the GEM fraction. Cells lacking CD45 showed identical phosphorylation
      of Lck in GEM and TX-100-soluble membranes. We propose that the GEM fraction
      represents a specific membrane domain present in T-cells, and that the
      hyperphosphorylation of tyrosine and lower kinase activity of GEM-associated Lck
      is due to exclusion of CD45 from these domains. Lck associated with the GEM
      domains may therefore consitute a reservoir of enzyme that can be readily
      activated.

PMID- 8978821
TI  - Actin and myosin function in directed vacuole movement during cell division in
      Saccharomyces cerevisiae.
AB  - During cell division, cytoplasmic organelles are not synthesized de novo, rather
      they are replicated and partitioned between daughter cells. Partitioning of the
      vacuole in the budding yeast Saccharomyces cerevisiae is coordinated with the
      cell cycle and involves a dramatic translocation of a portion of the parental
      organelle from the mother cell into the bud. While the molecular mechanisms that
      mediate this event are unknown, the vacuole's rapid and directed movements
      suggest cytoskeleton involvement. To identify cytoskeletal components that
      function in this process, vacuole inheritance was examined in a collection of
      actin mutants. Six strains were identified as being defective in vacuole
      inheritance. Tetrad analysis verified that the defect cosegregates with the
      mutant actin gene. One strain with a deletion in a myosin-binding region was
      analyzed further. The vacuole inheritance defect in this strain appears to result
      from the loss of a specific actin function; the actin cytoskeleton is intact and
      protein targeting to the vacuole is normal. Consistent with these findings, a
      mutation in the actin-binding domain of Myo2p, a class V unconventional myosin,
      abolishes vacuole inheritance. This suggests that Myo2p serves as a molecular
      motor for vacuole transport along actin filaments. The location of actin and
      Myo2p relative to the vacuole membrane is consistent with this model. Additional
      studies suggest that the actin filaments used for vacuole transport are dynamic,
      and that profilin plays a critical role in regulating their assembly. These
      results present the first demonstration that specific cytoskeletal proteins
      function in vacuole inheritance.

PMID- 8978822
TI  - Translocation of Src kinase to the cell periphery is mediated by the actin
      cytoskeleton under the control of the Rho family of small G proteins.
AB  - We have isolated Swiss 3T3 subclones that are resistant to the mitogenic and
      morphological transforming effects of v-Src as a consequence of aberrant
      translocation of the oncoprotein under low serum conditions. In chicken embryo
      and NIH 3T3 fibroblasts under similar conditions, v-Src rapidly translocates from
      the perinuclear region to the focal adhesions upon activation of the tyrosine
      kinase, resulting in downstream activation of activator protein-1 and mitogen
      activated protein kinase, which are required for the mitogenic and transforming
      activity of the oncoprotein. Since serum deprivation induces cytoskeletal
      disorganization in Swiss 3T3, we examined whether regulators of the cytoskeleton
      play a role in the translocation of v-Src, and also c-Src, in response to
      biological stimuli. Actin stress fibers and translocation of active v-Src to
      focal adhesions in quiescent Swiss 3T3 cells were restored by microinjection of
      activated Rho A and by serum. Double labeling with anti-Src and phalloidin
      demonstrated that v-Src localized along the reformed actin filaments in a pattern
      that would be consistent with trafficking in complexes along the stress fibers to
      focal adhesions. Furthermore, treatment with the actin-disrupting drug
      cytochalasin D, but not the microtubule-disrupting drug nocodazole, prevented v
      Src translocation. In addition to v-Src, we observed that PDGF-induced, Rac
      mediated membrane ruffling was accompanied by translocation of c-Src from the
      cytoplasm to the plasma membrane, an effect that was also blocked by cytochalasin
      D. Thus, we conclude that translocation of Src from its site of synthesis to its
      site of action at the cell membrane requires an intact cytoskeletal network and
      that the small G proteins of the Rho family may specify the peripheral
      localization in focal adhesions or along the membrane, mediated by their effects
      on the cytoskeleton.

PMID- 8978824
TI  - Native chick laminin-4 containing the beta 2 chain (s-laminin) promotes motor
      axon growth.
AB  - After denervation of muscle, motor axons reinnervate original synaptic sites. A
      recombinant fragment of the synapse specific laminin beta 2 chain (s-laminin) was
      reported to inhibit motor axon growth. Consequently, a specific sequence (leucine
      arginine-glutamate, LRE) of the laminin beta 2 chain was proposed to act as a
      stop signal and to mediate specific reinnervation at the neuromuscular junction
      (Porter, B.E., J. Weis, and J.R. Sanes. 1995. Neuron. 14:549-559). We demonstrate
      here that native chick laminin-4, which contains the beta 2 chain and is present
      in the synaptic basement membrane, does not inhibit but rather promotes motor
      axon growth. In native heterotrimeric laminin, the LRE sequence of the beta 2
      chain is found in a triple coiled-coil region that is formed by all three
      subunits. We show here that the effect of LRE depends on the structural context.
      Whereas a recombinant randomly coiled LRE peptide indeed inhibited outgrowth by
      chick motoneurons, a small recombinant triple coiled-coil protein containing this
      sequence did not.

PMID- 8978823
TI  - Functional N-methyl-D-aspartate receptors in O-2A glial precursor cells: a
      critical role in regulating polysialic acid-neural cell adhesion molecule
      expression and cell migration.
AB  - The capacity for long-distance migration of the oligodendrocyte precursor cell,
      oligodendrocyte-type 2 astrocyte (O-2A), is essential for myelin formation. To
      study the molecular mechanisms that control this process, we used an in vitro
      migration assay that uses neurohypophysial explants. We provide evidence that O
      2A cells in these preparations express functional N-methyl-D-aspartate (NMDA)
      receptors, most likely as homomeric complexes of the NR1 subunit. We show that
      NMDA evokes an increase in cytosolic Ca2+ that can be blocked by the NMDA
      receptor antagonist AP-5 and by Mg2+. Blocking the activity of these receptors
      dramatically diminished O-2A cell migration from explants. We also show that NMDA
      receptor activity is necessary for the expression by O-2A cells of the highly
      sialylated polysialic acid-neural cell adhesion molecule (PSA-NCAM) that is
      required for their migration. Thus, glutamate or glutamate receptor ligands may
      regulate O-2A cell migration by modulating expression of PSA-NCAM. These studies
      demonstrate how interactions between ionotropic receptors, intracellular
      signaling, and cell adhesion molecule expression influence cell surface
      properties, which in turn are critical determinants of cell migration.

PMID- 8978825
TI  - Cell adhesion molecules NgCAM and axonin-1 form heterodimers in the neuronal
      membrane and cooperate in neurite outgrowth promotion.
AB  - The axonal surface glycoproteins neuronglia cell adhesion molecule (NgCAM) and
      axonin-1 promote cell-cell adhesion, neurite outgrowth and fasciculation, and are
      involved in growth cone guidance. A direct binding between NgCAM and axonin-1 has
      been demonstrated using isolated molecules conjugated to the surface of
      fluorescent microspheres. By expressing NgCAM and axonin-1 in myeloma cells and
      performing cell aggregation assays, we found that NgCAM and axonin-1 cannot bind
      when present on the surface of different cells. In contrast, the cocapping of
      axonin-1 upon antibody-induced capping of NgCAM on the surface of CV-1 cells
      coexpressing NgCAM and axonin-1 and the selective chemical cross-linking of the
      two molecules in low density cultures of dorsal root ganglia neurons indicated a
      specific and direct binding of axonin-1 and Ng-CAM in the plane of the same
      membrane. Suppression of the axonin-1 translation by antisense oligonucleotides
      prevented neurite outgrowth in dissociated dorsal root ganglia neurons cultured
      on an NgCAM substratum, indicating that neurite outgrowth on NgCAM substratum
      requires axonin-1. Based on these and previous results, which implicated NgCAM as
      the neuronal receptor involved in neurite outgrowth on NgCAM substratum, we
      concluded that neurite outgrowth on an NgCAM substratum depends on two essential
      interactions of growth cone NgCAM: a trans-interaction with substratum NgCAM and
      a cis-interaction with axonin-1 residing in the same growth cone membrane.

PMID- 8978826
TI  - Angiotensin II regulation of neuromodulation: downstream signaling mechanism from
      activation of mitogen-activated protein kinase.
AB  - Angiotensin II (Ang II) stimulates expression of tyrosine hydroxylase and
      norepinephrine transporter genes in brain neurons; however, the signal
      transduction mechanism is not clearly defined. This study was conducted to
      determine the involvement of the mitogen-activated protein (MAP) kinase signaling
      pathway in Ang II stimulation of these genes. MAP kinase was localized in the
      perinuclear region of the neuronal soma. Ang II caused activation of MAP kinase
      and its subsequent translocation from the cytoplasmic to nuclear compartment,
      both effects being mediated by AT1 receptor subtype. Ang II also stimulated SRE-
      and AP1-binding activities and fos gene expression and its translocation in a MAP
      kinase-dependent process. These observations are the first demonstration of a
      downstream signaling pathway involving MAP kinase in Ang II-mediated
      neuromodulation in noradrenergic neurons.

PMID- 8978827
TI  - Identification of a cytoplasmic domain important in the polarized expression and
      clustering of the Kv2.1 K+ channel.
AB  - The voltage-sensitive K+ channel Kv2.1 has a polarized and clustered distribution
      in neurons. To investigate the basis for this localization, we expressed wild
      type Kv2.1 and two COOH-terminal truncation mutants, delta C318 and delta C187,
      in polarized epithelial MDCK cells. These functional channel proteins had
      differing subcellular localization, in that while both wild-type Kv2.1 and delta
      C187 localized to the lateral membrane in high density clusters, delta C318 was
      expressed uniformly on both apical and lateral membranes. A chimeric protein
      containing the hemagglutinin protein from influenza virus and the region of Kv2.1
      that differentiates the two truncation mutants (amino acids 536-666) was also
      expressed in MDCK cells, where it was found in high density clusters similar to
      those observed for Kv2.1. Polarized expression and clustering of Kv2.1 correlates
      with detergent solubility, suggesting that interaction with the detergent
      insoluble cytoskeleton may be necessary for proper localization of this channel.

PMID- 8978828
TI  - Integrins can collaborate with growth factors for phosphorylation of receptor
      tyrosine kinases and MAP kinase activation: roles of integrin aggregation and
      occupancy of receptors.
AB  - Integrins mediate cell adhesion, migration, and a variety of signal transduction
      events. These integrin actions can overlap or even synergize with those of growth
      factors. We examined for mechanisms of collaboration or synergy between integrins
      and growth factors involving MAP kinases, which regulate many cellular functions.
      In cooperation with integrins, the growth factors EGF, PDGF-BB, and basic FGF
      each produced a marked, transient activation of the ERK (extracellular signal
      regulated kinase) class of MAP kinase, but only if the integrins were both
      aggregated and occupied by ligand. Transmembrane accumulation of total tyrosine
      phosphorylated proteins, as well as nonsynergistic MAP kinase activation, could
      be induced by simple integrin aggregation, whereas enhanced transient
      accumulation of the EGF-receptor substrate eps8 required integrin aggregation and
      occupancy, as well as EGF treatment. Each type of growth factor receptor was
      itself induced to aggregate transiently by integrin ligand-coated beads in a
      process requiring both aggregation and occupancy of integrin receptors, but not
      the presence of growth factor ligand. Synergism was also observed between
      integrins and growth factors for triggering tyrosine phosphorylation of EGF,
      PDGF, and FGF receptors. This collaborative response also required both integrin
      aggregation and occupancy. These studies identify mechanisms in the signal
      transduction response to integrins and growth factors that require various
      combinations of integrin aggregation and ligands for integrin or growth factor
      receptors, providing opportunities for collaboration between these major
      regulatory systems.

PMID- 8978829
TI  - Expression of N-cadherin by human squamous carcinoma cells induces a scattered
      fibroblastic phenotype with disrupted cell-cell adhesion.
AB  - E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent,
      homotypic cell-cell adhesion and plays an important role in maintaining the
      normal phenotype of epithelial cells. Disruption of E-cadherin activity in
      epithelial cells correlates with formation of metastatic tumors. Decreased
      adhesive function may be implemented in a number of ways including: (a) decreased
      expression of E-cadherin; (b) mutations in the gene encoding E-cadherin; or (c)
      mutations in the genes that encode the catenins, proteins that link the cadherins
      to the cytoskeleton and are essential for cadherin mediated cell-cell adhesion.
      In this study, we explored the possibility that inappropriate expression of a
      nonepithelial cadherin by an epithelial cell might also result in disruption of
      cell-cell adhesion. We showed that a squamous cell carcinoma-derived cell line
      expressed N-cadherin and displayed a scattered fibroblastic phenotype along with
      decreased expression of E- and P-cadherin. Transfection of this cell line with
      antisense N-cadherin resulted in reversion to a normal-appearing squamous
      epithelial cell with increased E- and P-cadherin expression. In addition,
      transfection of a normal-appearing squamous epithelial cell line with N-cadherin
      resulted in downregulation of both E- and P-cadherin and a scattered fibroblastic
      phenotype. In all cases, the levels of expression of N-cadherin and E-cadherin
      were inversely related to one another. In addition, we showed that some squamous
      cell carcinomas expressed N-cadherin in situ and those tumors expressing N
      cadherin were invasive. These studies led us to propose a novel mechanism for
      tumorigenesis in squamous epithelial cells; i.e., inadvertent expression of a
      nonepithelial cadherin.

PMID- 8978832
TI  - Identification of retinoic acid receptor beta subtype specific agonists.

PMID- 8978830
TI  - HEMCAM, an adhesion molecule expressed by c-kit+ hemopoietic progenitors.
AB  - We have characterized the adhesion molecule HEMCAM, which is expressed by
      hemopoietic progenitors of embryonic bone marrow. HEMCAM belongs to the
      immunoglobulin superfamily and consists of the V-V-C2-C2-C2 Ig domains. There are
      three mRNA splice variants. One has a short cytoplasmic tail; another has a long
      tail; while the third seems to lack transmembrane and cytoplasmic regions. Except
      for the NH2-terminal sequence, HEMCAM is identical to gicerin, a molecular
      involved in neurite outgrowth and Wilm's kidney tumor progression in the chicken
      and it is significantly homologous with MUC18 a molecule involved in melanoma
      progression and metastasis in human beings. In the bone marrow the HEMCAM+ cell
      population contains c-kit+ subsets. HEMCAM+ cells coexpressing the receptor
      tyrosine kinase c-kit give rise to T cells at a frequency of 0.17 when injected
      intrathymically in congenic animals. As HEMCAM+, c-kit+ cells differentiate into
      myeloid and erythroid CFU's the double-positive cell population seems to contain
      precursors for multiple lineages. HEMCAM promotes cell-cell adhesion of
      transfected cells. Cross-linking of murine HEMCAM leads to cell spreading of T
      lymphocyte progenitors adhering to the vascular adhesion molecules, PECAM-1 and
      VCAM-1. Thus, HEMCAM is likely to be involved in cellular adhesion and homing
      processes.

PMID- 8978831
TI  - Rescue of mammary epithelial cell apoptosis and entactin degradation by a tissue
      inhibitor of metalloproteinases-1 transgene.
AB  - We have used transgenic mice overexpressing the human tissue inhibitor of
      metalloproteinases (TIMP)-1 gene under the control of the ubiquitous beta-actin
      promoter/enhancer to evaluate matrix metalloproteinase (MMP) function in vivo in
      mammary gland growth and development. By crossing the TIMP-1 transgenic animals
      with mice expressing an autoactivating stromelysin-1 transgene targeted to
      mammary epithelial cells, we obtained a range of mice with genetically engineered
      proteolytic levels. The alveolar epithelial cells of mice expressing
      autoactivating stromelysin-1 underwent unscheduled apoptosis during late
      pregnancy. When stromelysin-1 transgenic mice were crossed with mice
      overexpressing TIMP-1, apoptosis was extinguished. Entactin (nidogen) was a
      specific target for stromelysin-1 in the extracellular matrix. The enhanced
      cleavage of basement membrane entactin to above-normal levels was directly
      related to the apoptosis of overlying mammary epithelial cells and paralleled the
      extracellular MMP activity. These results provide direct evidence for cleavage of
      an extracellular matrix molecule by an MMP in vivo.

PMID- 8978833
TI  - Inhibitors of acyl-CoA: cholesterol O-acyl transferase (ACAT) as
      hypocholesterolemic agents. CI-1011: an acyl sulfamate with unique cholesterol
      lowering activity in animals fed noncholesterol-supplemented diets.

PMID- 8978834
TI  - Bicyclic N-hydroxyurea inhibitors of 5-lipoxygenase: pharmacodynamic,
      pharmacokinetic, and in vitro metabolic studies characterizing N-hydroxy-N-(2,3
      dihydro-6-(phenylmethoxy)-3-benzofuranyl)urea.
AB  - A series of N-hydroxyurea derivatives have been prepared and examined as
      inhibitors of 5-lipoxygenase. Oral activity was established by examining the
      inhibition of LTB4 biosynthesis in an ex vivo assay in the mouse. The
      pharmacodynamic performance in the mouse of selected compounds was assessed using
      an ex vivo LTB4 assay and an adoptive peritoneal anaphylaxis assay at extended
      pretreat times. Compounds with an extended duration of action were re-examined as
      the individual enantiomers in the ex vivo assay, and the (S) enantiomer of N
      hydroxy-N-[2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl]urea, (+)-1a (SB 202235),
      was selected as the compound with the best overall profile. Higher plasma
      concentrations and longer plasma half-lives were found for (+)-1a relative to its
      enantiomer in the mouse, monkey, and dog. In vitro metabolic studies in mouse
      liver microsomes established enantiospecific glucuronidation as a likely
      mechanism for the observed differences between the enantiomers of 1a.
      Enantioselective glucuronidation favoring (-)-1a was also found in human liver
      microsomes.

PMID- 8978835
TI  - Indole derivatives as a new class of steroid 5 alpha-reductase inhibitors.
AB  - A series of indole derivatives with varied substituents on the alpha, beta
      unsaturated double bond were synthesized and evaluated for their ability to
      inhibit rat prostatic 5 alpha-reductase. Compounds possessing an ethyl
      substituent at the beta-position of the double bond showed potent inhibitory
      activity. Among them, (Z)-4-{2-[[3-[1-(4,4'-difluorobenzhydryl)indol-5-yl]-2
      pentenoy l]- amino]phenoxy}butyric acid (16, KF20405) showed the maximum potency
      with an IC50 value of 0.48 +/- 0.086 nM, which was 20-fold higher potency than 1
      (MK-906). Compound 16 effectively inhibited DHT production 4 h after a 3 mg/kg
      oral administration. Several potent indole derivatives, 1 and 2 ((+/-)-ONO-3805),
      were tested versus rat and human isozymes. Nonsteroidal inhibitors such as indole
      derivatives and 2 were 2-3 orders of magnitude less potent for human type 2
      isozyme than steroidal inhibitor 1 and expressed a significant species deference
      for these isozymes.

PMID- 8978836
TI  - Synthesis and biological activity of metabolites of the antidiabetic,
      antihyperglycemic agent pioglitazone.
AB  - Pioglitazone (5-(4-(2-(5-ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione, 2)
      is a prototypical antidiabetic thiazolidinedione that had been evaluated for
      possible clinical development. Metabolites 6-9 have been identified after dosing
      of rats and dogs. Ketone 10 has not yet been identified as a metabolite but has
      been added to the list as a putative metabolite by analogy to alcohol 6 and
      ketone 7. We have developed improved syntheses of pioglitazone (2) metabolites 6
      9 and the putative metabolite ketone 10. These entities have been compared in the
      KKAy mouse model of human type-II diabetes to pioglitazone (2). Ketone 10 has
      proven to be the most potent of these thiazolidinedinediones in this in vivo
      assay. When 6-10 were compared in vitro in the 3T3-L1 cell line to 2, for their
      ability to augment insulin-stimulated lipogenesis, 10 was again the most potent
      compound with 6, 7 and 9 roughly equivalent to 2. These data suggest that
      metabolites 6, 7 and 9 are likely to contribute to the pharmacological activity
      of pioglitazone (2), as had been previously reported for ciglitazone (1).

PMID- 8978837
TI  - Structure-based alignment and comparative molecular field analysis of
      acetylcholinesterase inhibitors.
AB  - The method of comparative molecular field analysis (CoMFA) was used to develop
      quantitative structure-activity relationships for physostigmine, 9-amino-1,2,3,4
      tetrahydroacridine (THA), edrophonium (EDR), and other structurally diverse
      inhibitors of acetylcholinesterase (AChE). The availability of the crystal
      structures of enzyme/inhibitor complexes (EDR/AChE, THA/AChE, and decamethonium
      (DCM)/AChE) (Harel, M.; et al. Quaternary ligand binding to aromatic residues in
      the active-site gorge of acetylcholinesterase. Proc. Natl. Acad. Sci. U.S.A.
      1993, 90, 9031-9035) provided information regarding not only the active
      conformation of the inhibitors but also the relative mutual orientation of the
      inhibitors in the active site of the enzyme. Crystallographic conformations of
      EDR and THA were used as templates onto which additional inhibitors were
      superimposed. The application of cross-validated R2 guided region selection
      method, recently developed in this laboratory (Cho, S.J.; Tropsha, A. Cross
      Validated R2 Guided Region Selection for Comparative Molecular Field Analysis
      (CoMFA): A Simple Method to Achieve Consistent Results. J. Med. Chem. 1995, 38,
      1060-1066), to 60 AChE inhibitors led to a highly predictive CoMFA model with the
      q2 of 0.734.

PMID- 8978838
TI  - Design, synthesis, and evaluation of nonpeptidic inhibitors of human rhinovirus
      3C protease.
AB  - The design, synthesis, and biological evaluation of reversible, nonpeptidic
      inhibitors of human rhinovirus (HRV) 3C protease (3CP) are reported. A novel
      series of 2,3-dioxindoles (isatins) were designed that utilized a combination of
      protein structure-based drug design, molecular modeling, and structure-activity
      relationship (SAR). The C-2 carbonyl of isatin was envisioned to react in the
      active site of HRV 3CP with the cysteine responsible for catalytic proteolysis,
      thus forming a stabilized transition state mimic. Molecular-modeling experiments
      using the apo crystal structure of human rhinovirus-serotype 14 (HRV-14) 3CP and
      a peptide substrate model allowed us to design recognition features into the P1
      and P2 subsites, respectively, from the 5- and 1-positions of isatin. Attempts to
      optimize recognition properties in the P1 subsite using SAR at the 5-position
      were performed. In addition, a series of ab initio calculations were carried out
      on several 5-substituted isatins to investigate the stability of sulfide adducts
      at C-3. The inhibitors were prepared by general synthetic methods, starting with
      commercially available 5-substituted isatins in nearly every case. All compounds
      were tested for inhibition of purified HRV-14 3CP. Compounds 8, 14, and 19 were
      found to have excellent selectivity for HRV-14 3CP compared to other proteolytic
      enzymes, including chymotrypsin and cathepsin B. Selected compounds were assayed
      for antiviral activity against HRV-14-infected HI-HeLa cells. A 2.8 A cocrystal
      structure of derivative 19 covalently bound to human rhinovirus-serotype 2 (HRV
      2) 3CP was solved and revealed that the isatin was situated in essentially the
      same conformation as modeled.

PMID- 8978839
TI  - Synthesis, structure-activity relationships, and molecular modeling studies of N
      (indol-3-ylglyoxylyl)benzylamine derivatives acting at the benzodiazepine
      receptor.
AB  - A number of N-(indol-3-ylglyoxylyl)benzylamine derivatives were synthesized and
      tested for [3H]flunitrazepam displacing activity in bovine brain membranes. Some
      of these derivatives (9, 12, 14, 15, 17, 27, 34, 35, 38, 41, and 45) exhibited
      high affinity for the benzodiazepine receptor (BzR) with Ki values ranging from
      67 to 11 nM. The GABA ratio and [35S]-tert-butylbicyclophosphorothionate binding
      data, determined for the most active compounds, showed that they elicit an
      efficacy profile at the BzR which depends on the kind of substituent present on
      the phenyl ring of the benzylamine moiety. Moreover, lengthening (propylamine
      derivatives 1-3) and shortening (aniline derivatives 46-54) of the distance
      between the phenyl ring and the amide group of the side chain gave compounds with
      a drastically lower binding potency. The biological results are discussed in the
      light of a recently proposed pharmacophore model and compared, by molecular
      modeling studies, with those obtained from effective BzR ligands.

PMID- 8978840
TI  - Synthesis and bioevaluation of delta 7-5-desaturase inhibitors, an enzyme late in
      the biosynthesis of the fungal sterol ergosterol.
AB  - Ergosterol, the predominant sterol of fungi, is postulated to have many cellular
      functions which include a bulk membrane role and a regulatory role. Studies with
      sterol auxotrophs show that, even in the presence of sterols which can fulfill
      the bulk membrane requirements, a small concentration of ergosterol is absolutely
      necessary for growth. The delta 5-double bond appears to be required for the
      regulatory role of ergosterol; therefore, development of inhibitors of the enzyme
      that introduce this double bond, delta 7-sterol 5-desaturase (5-desaturase), may
      lead to effective antifungal agents. Within is the first reported synthesis of
      inhibitors of fungal 5-desaturase and the development of an in vitro tritium
      efficacy radioassay. The inhibitors were of the general structure 7,22(E)
      ergostadien-3 beta-ol with alpha-face heteroatom substituents in the vicinity of
      C-5. They exhibited IC50 values of 47-149 microM.

PMID- 8978841
TI  - 2'-O-aminopropyl ribonucleotides: a zwitterionic modification that enhances the
      exonuclease resistance and biological activity of antisense oligonucleotides.
AB  - Oligonucleotides containing 2'-O-aminopropyl-substituted RNA have been
      synthesized. The 2'-O-(aminopropyl)adenosine (APA), 2'-O-(aminopropyl)cytidine
      (APC), 2'-O-(aminopropyl)-guanosine (APG), and 2'-O-(aminopropyl)uridine (APU)
      have been prepared in high yield from the ribonucleoside, protected, and
      incorporated into an oligonucleotide using conventional phosphoramidite
      chemistry. Molecular dynamics studies of a dinucleotide in water demonstrates
      that a short alkylamine located off the 2'-oxygen of ribonucleotides alters the
      sugar pucker of the nucleoside but does not form a tight ion pair with the
      proximate phosphate. A 5-mer with the sequence ACTUC has been characterized using
      NMR. As predicted from the modeling results, the sugar pucker of the APU moiety
      is shifted toward a C3'-endo geometry. In addition, the primary amine rotates
      freely and is not bound electrostatically to any phosphate group, as evidenced by
      the different sign of the NOE between sugar proton resonances and the signals
      from the propylamine chain. Incorporation of aminopropyl nucleoside residues into
      point-substituted and fully modified oligomers does not decrease the affinity for
      complementary RNA compared to 2'-O-alkyl substituents of the same length.
      However, two APU residues placed at the 3'-terminus of an oligomer gives a 100
      fold increase in resistance to exonuclease degradation, which is greater than
      observed for phosphorothioate oligomers. These structural and biophysical
      characteristics make the 2'-O-aminopropyl group a leading choice for
      incorporation into antisense therapeutics. A 20-mer phosphorothioate
      oligonucleotide capped with two phosphodiester aminopropyl nucleotides targeted
      against C-raf mRNA has been transfected into cells via electroporation. This
      oligonucleotide has 5-10-fold greater activity than the control phosphorothioate
      for reducing the abundance of C-raf mRNA and protein.

PMID- 8978842
TI  - Synthesis and evaluation of two positron-labeled nitric oxide synthase
      inhibitors, S-[11C]methylisothiourea and S-(2-[18F]fluoroethyl)isothiourea, as
      potential positron emission tomography tracers.
AB  - In an effort to develop a tracer for probing inducible nitric oxide synthase
      (iNOS) levels in vivo utilizing positron emission tomography, we have synthesized
      and evaluated two positron-emitting iNOS selective inhibitors: S
      [11C]methylisothiourea (1b) and S-(2-[18F]fluoroethyl)-isothiourea (3b). Prior to
      fluorine-18 labeling, the nonradioactive fluoro derivative S-(2
      fluoroethyl)isothiourea (3a) was prepared and determined to have a 9-fold higher
      selectivity for iNOS compared to endothelial NOS (eNOS). Radiochemical synthesis
      of both compounds, in high radiochemical purity and at high specific activity,
      was accomplished by the S-alkylation reaction of labeled precursors (11CH3I or
      18FCH2CH2OTf) with thiourea. An in vitro model, J774 macrophage cell line, was
      used to assess the uptake of radiolabeled iNOS inhibitor in response to iNOS
      induction at the cellular level. Increased cell uptake of these two labeled
      compounds at stimulated iNOS levels, as well as blocking under controlled in
      vitro conditions, was observed. Lipophilicity (log P o/w), stability, and tissue
      biodistribution data of both compounds are reported. Serum stability studies
      indicate that 3b metabolized much more rapidly compared to the relatively stable
      1b in vitro and in vivo. Based on in vitro cell uptake data, both tracers were
      further evaluated in lipopolysaccharide (LPS)-pretreated rats. LPS has been
      reported to induce iNOS protein expression in the liver, lung, heart, and kidney
      and other tissues. The uptake for LPS-pretreated rats (6 h post-treatment) was
      significantly increased in the liver, kidney, and heart for 3b at 10 min and in
      the liver and lung for 1b at 30 min. The results suggest that this first
      generation of radiolabeled inhibitors may be useful for assessing induction of
      iNOS in vivo with PET.

PMID- 8978843
TI  - Indole inhibitors of human nonpancreatic secretory phospholipase A2. 2. Indole-3
      acetamides with additional functionality.
AB  - As reported in our previous paper, a series of indole-3-acetamides which
      possessed potency and selectivity as inhibitors of human nonpancreatic secretory
      phospholipase A2(hnps-PLA2) was developed. The design of these compounds was
      based on information derived from x-ray crystal structures determined for
      complexes between the enzyme and its inhibitors. We describe here the further
      implementation of this structure-based design strategy and continued SAR
      development to produce indole-3-acetamides with additional functionalities which
      provide increased interaction with important residues within the enzyme active
      site. These efforts led to inhibitors with substantially enhanced potency and
      selectivity.

PMID- 8978844
TI  - Indole inhibitors of human nonpancreatic secretory phospholipase A2. 3. Indole-3
      glyoxamides.
AB  - The preceding papers of this series detail the development of functionalized
      indole-3-acetamides as inhibitors of hnps-PLA2. We describe here the extension of
      the structure-activity relationship to include a series of indole-3-glyoxamide
      derivatives. Functionalized indole-3-glyoxamides with an acidic substituent
      appended to the 4- or 5-position of the indole ring were prepared and tested as
      inhibitors of hnps-PLA2. It was found that the indole-3-glyoxamides with a 4
      oxyacetic acid substituent had optimal inhibitory activity. These inhibitors
      exhibited an improvement in potency over the best of the indole-3-acetamides, and
      LY315920 (6m) was selected for evaluation clinically as an hnps-PLA2 inhibitor.

PMID- 8978845
TI  - Studies on disease-modifying antirheumatic drugs: synthesis of novel quinoline
      and quinazoline derivatives and their anti-inflammatory effect.
AB  - In the course of our study aimed at developing new types of DMARDs (disease
      modifying antirheumatic drugs), we found that quinoline derivative 1a had a
      potent anti-inflammatory effect in an adjuvant arthritis (AA) rat model, starting
      from the potent bone resorption inhibitors justicidins as the lead compounds.
      Further modification of 1a was performed, and various quinoline and quinazoline
      derivatives having a heteroaryl moiety on the alkyl side chain at the 2-position
      of the skeleton were prepared. These compounds were evaluated for anti
      inflammatory effects using the AA rat model. Most of these compounds, especially
      those having an imidazole or a triazole moiety on the 2-alkyl chain, exhibited a
      potent effect. Among the compounds synthesized, ethyl 4-(3,4-dimethoxyphenyl)-6,7
      dimethoxy-2-(1,2, 4-triazol-1-yl-methyl)quinoline-3-carboxylate (12d), having an
      ED50 value of 2.6 mg/kg/day (anti-inflammatory effect in an AA rat model, po),
      was selected as a candidate for further investigation. In vitro, 12d inhibited
      mitogen-induced proliferation at 10(-7)-10(-5) M but not prostaglandin E2
      production at 10(-5) M. Moreover, 12d preferentially inhibited the IFN-gamma
      production by Th1-type clones over the IL-4 production by Th2-type clones. This
      preferential suppression of Th1 cytokine production is considered the essential
      immunomodulating action of 12d for the present. Synthesis and structure-activity
      relationships for this novel series of quinoline and quinazoline derivatives are
      detailed.

PMID- 8978846
TI  - Synthesis and phospholipase A2 inhibitory activity of thielocin B3 derivatives.
AB  - We prepared several types of derivatives of thielocin B3, a very potent naturally
      occurring inhibitor for human nonpancreatic secretory PLA2 (sPLA2-II), and
      conducted a structure-activity relationship study to identify potent sPLA2-II
      inhibitors with the aim of developing antiinflammatory drugs. The total number of
      aromatic rings is critical for sPLA2-II inhibition, and the best result was
      obtained in the case of six rings. The structure of the central part of the
      inhibitors was not specific, and potent inhibitors were found among the sulfide,
      sulfone, ether, methylene, and amino derivatives. Although a diester of the
      terminal carboxylic acid lost its inhibitory activity, having both of the
      carboxylic acids was not necessary for expression of activity, as illustrated by
      a glycine derivative with the benzyl ester group 36. Among the newly synthesized
      derivatives, 18, 20, 29, and 36 showed very potent human sPLA2-II inhibitory
      activity comparable to that of natural thielocin B3. Their IC50 values are in the
      range 0.069-0.14 microM, and they are a class of compounds showing the most
      potent sPLA2-II inhibition to date.

PMID- 8978847
TI  - Mechanism of selective incorporation of the melanoma seeker 2-thiouracil into
      growing melanin.
AB  - The mechanism of selective incorporation of 2-thiouracil (TU), a highly specific
      melanoma seeker, into growing melanins was investigated both in vitro and in
      vivo. Methods used included direct analysis of the melanins, by evaluation of the
      absorption at 350 nm (A350) and chemical degradation coupled with HPLC
      quantitation of pigment makers, i.e., pyrrole-2,3-dicarboxylic acid (PDCA) and
      pyrrole-2,3,5-tricarboxylic acid (PTCA), as well as biosynthetic experiments
      involving tyrosinase-catalyzed oxidation of DOPA, 5,6-dihydroxyindole (DHI), and
      5,6-dihydroxyindole-2-carboxylic acid (DHICA). Injection of radiolabeled TU into
      melanoma-bearing mice resulted in a rapid incorporation of the drug into the
      tumor pigment, with a substantial decrease in A350 and in PTCA yields. Similar
      changes in the absorption properties were observed in biosynthetic melanins
      prepared in the presence of TU, whereas the yields of PTCA and PDCA varied
      depending on the pigment precursor used. When incubated with DOPA in the presence
      of tyrosinase, TU profoundly modified the normal course of melanogenesis,
      favoring formation of a complex mixture of addition products consisting mainly of
      6-S-thiouracil-DOPA as well as DHI-TU adducts. The latter were obtained in larger
      amounts by enzymatic oxidation of DHI in the presence of TU and were identified
      as the 3- and 2-substituted adducts 1 and 2, the dimer 3, and the trimer 4.
      Similar reactions carried out on DHICA yielded the 4-substituted adduct 5, the
      dimer 6, and the trimer 7. A new mechanistic scheme for the incorporation of TU
      into growing melanin is proposed, which envisages nucleophilic attack of the
      thioureylene moiety of TU to transient quinonoid intermediates in the melanin
      pathway, chiefly dopaquinone and 5,6-indolequinones, followed by entrainment of
      the resulting adducts into the growing pigment via oxidative copolymerization
      with DHICA and/or DHI.

PMID- 8978848
TI  - Synthesis, biotransformation, and pharmacokinetic studies of 9-(beta-D
      arabinofuranosyl)-6-azidopurine: a prodrug for ara-A designed to utilize the
      azide reduction pathway.
AB  - As a part of our efforts to design prodrugs for antiviral nucleosides, 9-(beta-D
      arabinofuranosyl)-6-azidopurine (6-AAP) was synthesized as a prodrug for ara-A
      that utilizes the azide reduction biotransformation pathway. 6-AAP was
      synthesized from ara-A via its 6-chloro analogue 4. The bioconversion of the
      prodrug was investigated in vitro and in vivo, and the pharmacokinetic parameters
      were determined. For in vitro studies, 6-AAP was incubated in mouse serum and
      liver and brain homogenates. The half-lives of 6-AAP in serum and liver and brain
      homogenates were 3.73, 4.90, and 7.29 h, respectively. 6-AAP was metabolized
      primarily in the liver homogenate microsomal fraction by the reduction of the
      azido moiety to the amine, yielding ara-A. However, 6-AAP was found to be stable
      to adenosine deaminase in a separate in vitro study. The in vivo metabolism and
      disposition of ara-A and 6-AAP were conducted in mice. When 6-AAP was
      administered by either oral or intravenous route,the half-life of ara-A was 7-14
      times higher than for ara-A administered intravenously. Ara-A could not be found
      in the brain after the intravenous administration of ara-A. However, after 6-AAP
      administration (by either oral or intravenous route), significant levels of ara-A
      were found in the brain. The results of this study demonstrate that 6-AAP is
      converted to ara-A, potentially increasing the half-life and the brain delivery
      of ara-A. Further studies to utilize the azide reduction approach on other
      clinically useful agents containing an amino group are in progress in our
      laboratories.

PMID- 8978849
TI  - Antitumor properties of some 2-[(dimethylamino)methyl]phenylgold(III) complexes.
AB  - Four analogues of the gold(III) complex [AuCl2(damp)] (1) (damp = 2
      [(dimethylamino)methyl]phenyl) have been evaluated for antitumor activity. The
      compounds have structural features in common with cisplatin which was included as
      a comparison in the study. In vitro, against a panel of cell lines established
      from tumors of different tissue types, the gold complexes showed broadly similar
      growth inhibitory properties with some selectivity to the HT1376 bladder cell
      line. In a panel of human ovarian carcinoma cell lines, non-cross-resistance to
      cisplatin was observed, for the complexes, in an acquired cisplatin-resistant
      line. In vivo, using subcutaneously implanted xenografts derived from the HT1376
      bladder and CH1 ovarian cell lines, [Au(acetato)2(damp)] (3) and
      [Au(malonato)(damp)] (5) (administered intraperitoneally) gave significant tumor
      inhibition. Mechanistic studies performed with compound 3 showed marked
      differences to cisplatin. Thus, much higher concentrations of the gold compound
      were required to affect Col E1 plasmid mobility, and an alkaline elution study
      showed that 3 did not cause interstrand DNA cross-links in SK-OV-3 cells.
      Exposure of SK-OV-3 cells to 3 induced only relatively minor changes in cell
      cycle distribution. Furthermore 3 was only marginally active in vivo against the
      cisplatin-sensitive murine ADJ/PC6 plasmacytoma. In summary, the gold-(III)
      complexes 3 and 5 exhibited selective cytotoxicity in vitro and showed in vivo
      antitumor activity against human carcinoma xenografts. Also, although 3 has some
      structural similarity to cisplatin, its mode of action appears to be different.

PMID- 8978851
TI  - Synthesis and angiotensin II receptor antagonistic activities of benzimidazole
      derivatives bearing acidic heterocycles as novel tetrazole bioisosteres.
AB  - The design, synthesis, and biological activity of benzimidazole-7-carboxylic
      acids bearing 5-oxo-1,2,4-oxadiazole, 5-oxo-1,2,4-thiadiazole, 5-thioxo-1,2,4
      oxadiazole, and 2-oxo-1,2,3,5-oxathiadiazole rings are described. These compounds
      were efficiently prepared from the key intermediates, the amidoximes 4. The
      synthesized compounds were evaluated for in vitro and in vivo angiotensin II
      (AII) receptor antagonistic activities. Most were found to have high affinity for
      the AT1 receptor (IC50 value, 10(-6)-10(-7)M) and to inhibit the AII-induced
      pressor response (more than 50% inhibition at 1 mg/kg po). The 5-oxo-1,2,4
      oxadiazole, 5-oxo-1,2,4-thiadiazole, and 5-thioxo-1,2,4-oxadiazole derivatives
      showed stronger inhibitory effects than the corresponding tetrazole derivatives,
      while their binding affinities were weaker. This might be ascribed to their
      improved bioavailability by increased lipophilicity. The 5-oxo-1,2,4-oxadiazole
      derivative 2 (TAK-536) and 5-oxo-1,2,4-thiadiazole derivative 8f showed efficient
      oral bioavailability without prodrug formation. This study showed that the 5-oxo
      1,2,4-oxadiazole ring and its thio analog, the 5-oxo-1,2,4-thiadiazole ring,
      could be lipophilic bioisosteres for the tetrazole ring in nonpeptide AII
      receptor antagonists.

PMID- 8978850
TI  - Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs
      that are highly selective for protein kinase C over protein kinase A.
AB  - A series of balanol analogs in which the perhydroazepine ring and the p
      hydroxybenzamide moiety were combined into an acyclic linked unit have been
      prepared and evaluated for their inhibitory properties against the
      serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors
      of the alpha, beta I, beta II, gamma, delta, epsilon and eta PKC isozymes were
      prepared. In general, these acyclic balanol analogs were found to be highly
      selective for PKC over the serine/threonine kinase PKA. The type and number of
      atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for
      optimal PKC inhibition were investigated. The most potent compounds contained a
      three-carbon linker in which the carboxamide moiety of balanol had been replaced
      by a methylene group. The effect of placing substituents on the three-carbon
      chain was also investigated. The preferred compounds contained either a 2
      benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds
      6b and 21b were tested against a panel of serine/threonine kinases and found to
      be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10
      fold more active than the R-enantiomer against the PKC isozymes. The effect of
      making the analogs more rigid by making the three-carbon chain part of a five
      membered ring, but with retention of the methylene replacement for the
      carboxamide moiety, led to potent PKC inhibitors including anti-substituted
      pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti
      substituted cyclopentane analog 29b. The anti cyclopentane analog 29b, was a low
      micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its
      carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally
      esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into
      low-micromolar inhibitors of neutrophils.

PMID- 8978852
TI  - Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor
      agonist activity (II): Optimization of the C3 amino substituent.
AB  - Analogs of the previously reported 1,5-benzodiazepine peripheral cholecystokinin
      (CCK-A) receptor agonist 1 were prepared which explore substitution and/or
      replacement of the C-3 phenyl urea moiety. Agonist efficacy on the isolated
      guinea pig gallbladder (GPGB) was retained with a variety of substituted ureas
      and amide analogs. Three compounds were identified which were orally active in
      the mouse gallbladder emptying assay (MGBE). The 2-indolamide (52) and N
      (carboxymethyl)-2-indolamide (54) derivatives had improved affinity for the human
      CCK-A receptor but reduced agonist efficacy on the GPGB. Neither indolamide was
      orally active in a rat feeding assay. In contrast, the (3-carboxyphenyl)urea
      derivative (29, GW7854) had moderately increased affinity for the human CCK-B
      receptor but was a potent full agonist on the GPGB and was orally active in both
      the MGBE and rat feeding assays. GW7854 was a full agonist (EC50 = 60 nM) for
      calcium mobilization on CHO K1 cells expressing hCCK-A receptors and a potent
      antagonist of CCK-8 (pA2 = 9.1) on CHO K1 cells expressing hCCK-B receptors.
      GW7854 is a potent mixed CCK-A agonist/CCK-B antagonist which is orally active in
      two in vivo models of CCK-A-mediated agonist activity.

PMID- 8978853
TI  - Genetic neural networks for quantitative structure-activity relationships:
      improvements and application of benzodiazepine affinity for benzodiazepine/GABAA
      receptors.
AB  - A novel tool, called a genetic neural network (GNN), has been developed for
      obtaining quantitative structure-activity relationships (QSAR) for high
      dimensional data sets (J. Med. Chem. 1996, 39, 1521-1530). The GNN method uses a
      neural network to correlate activity with descriptors that are preselected by a
      genetic algorithm. To provide an extended test of the GNN method, the data on 57
      benzodiazepines given by Maddalena and Johnston (MJ; J. Med. Chem. 1995, 38, 715
      724) have been examined with an enhanced version of GNN, and the results are
      compared with the excellent QSAR of MJ. The problematic steepest descent training
      has been replaced by the scaled conjugate gradient algorithm. This leads to a
      substantial gain in performance in both robustness of prediction and speed of
      computation. The cross-validation GNN simulation and the subsequent run based on
      an unbiased and more efficient protocol led to the discovery of other 10
      descriptor QSARs that are superior to the best model of MJ based on backward
      elimination selection and neural network training. Results from a series of GNNs
      with a different number of inputs showed that a neural network with fewer inputs
      can produce QSARs as good as or even better than those with higher dimensions.
      The top-ranking models from a GNN simulation using only six input descriptors are
      presented, and the chemical significance of the chosen descriptors is discussed.
      The statistical significance of these GNN QSARs is validated. The best QSARs are
      used to provide a graphical tool that aids the design of new drug analogues. By
      replacing functional groups at the 7- and 2'-positions with ones that have
      optimal substituent parameters, a number of new benzodiazepines with high potency
      are predicted.

PMID- 8978854
TI  - Polyamine analogue regulation of NMDA MK-801 binding: a structure-activity study.
AB  - A series of analogues and homologues of spermine were synthesized, and their
      impact on MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor was
      evaluated. These tetraamines encompass both linear and cyclic compounds. The
      linear molecules include norspermine, N1, N11-diethylnorspermine, N1,N12
      bis(2,2,2-trifluoroethyl)spermine, homospermine, and N1,N14-diethylhomospermine.
      The cyclic tetraamines consist of the piperidine analogues N1,N3-bis(4
      piperidinyl)-1,3-diaminopropane, N1,N4-bis(4-piperidinyl)-1,4-diaminobutane,
      N1,N4-bis(4-piperidinylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4
      piperidinyl)ethyl]-1,4-diaminobutane and the pyridine analogues N1,N3-bis(4
      pyridyl)-1,3-diaminopropane, N1,N4-bis(4-pyridyl)-1,4-diaminobutane, N1,N4-bis(4
      pyridylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4-pyridyl)-ethyl]-1,4
      diaminobutane. This structure-activity set makes it possible to establish the
      importance of charge, intercharge distance, and terminal nitrogen substitution on
      polyamine-regulated MK-801 binding in the NMDA channel. Four families of
      tetraamines are included in this set: norspermines, spermines, homospermines, and
      tetraazaoctadecanes. Calculations employing a SYBYL modeling program revealed
      that the distance between terminal nitrogens ranges between 12.62 and 19.61 A.
      The tetraamines are constructed such that within families cyclics and acyclics
      have similar lengths but different nitrogen pKa's and thus different protonation,
      or charge, states at physiological pH. The pKa values for all nitrogens of each
      molecule and its protonation state at physiological pH are described. The
      modifications at the terminal nitrogens include introduction of ethyl and
      beta,beta,beta-trifluoroethyl groups and incorporation into piperidinyl or
      pyridyl systems. The studies clearly indicate that polyamine length, charge, and
      terminal nitrogen substitution have a significant effect on how the tetraamine
      regulates MK-801 binding to the NMDA receptor. Thus a structure-activity basis
      set on which future design of MK-801 agonists and antagonists can be based is now
      available.

PMID- 8978855
TI  - Synthesis and bioactivity of novel bis(heteroaryl)piperazine (BHAP) reverse
      transcriptase inhibitors: structure-activity relationships and increased
      metabolic stability of novel substituted pyridine analogs.
AB  - The major route of metabolism of the bis(heteroaryl)piperazine (BHAP) class of
      reverse transcriptase inhibitors (RTIs), atevirdine and delavirdine, is via
      oxidative N-dealkylation of the 3-ethyl- or 3-isopropylamino substituent on the
      pyridine ring. This metabolic pathway is also the predominant mode of metabolism
      of (alkylamino)piperidine BHAP analogs (AAP-BHAPs), compounds wherein a 4
      (alkylamino)piperidine replaces the piperazine ring of the BHAPs. The novel AAP
      BHAPs possess the ability to inhibit non-nucleoside reverse transcriptase
      inhibitor (NNRTI) resistant recombinant HIV-1 RT and NNRTI resistant variants of
      HIV-1. This report describes an approach to preventing this degradation which
      involves the replacement of the 3-ethyl- or 3-isopropylamino substituent with
      either a 3-tert-butylamino substituent or a 3-alkoxy substituent. The synthesis,
      bioactivity and metabolic stability of these analogs is described. The majority
      of analogs retain inhibitory activities in enzyme and cell culture assays. In
      general, a 3-ethoxy or 3-isopropoxy substituent on the pyridine ring, as in
      compounds 10, 20, or 21, resulted in enhanced stabilities. The 3-tert-butylamino
      substituent was somewhat beneficial in the AAP-BHAP series of analogs, but did
      not exert a significant effect in the BHAP series. Lastly, the nature of the
      indole substitution sometimes plays a significant role in metabolic stability,
      particularly in the BHAP series of analogs.

PMID- 8978856
TI  - Synthesis and HIV inhibition activity of 2',3'-dideoxy-3'-C-hydroxymethyl
      nucleosides.
AB  - A series if 2',3'-dideoxy-3'-C-hydroxymethyl purine nucleosides were prepared
      based on the photochemical ring expansion of a chiral cyclobutanone precursor,
      (2S)-trans-2,3-bis[(benzoyloxy)methyl]cyclobutanone, in the presence of a 6
      substituted purine. Both alpha- and beta-anomers are produced in this
      transformation. Deprotection was effected by reaction of the photoadducts with
      saturated methanolic ammonia. Nine purine nucleosides were tested for their
      inhibitory effect of HIV IIIB virus on H9 cells. The 6-hexyloxy and adenine
      derivatives 4e,c, respectively, appeared to be most effective at inhibiting viral
      reproduction with 4c comparable in activity to ddI and AZT.

PMID- 8978857
TI  - Structure-activity relationships of phomactin derivatives as platelet activating
      factor antagonists.
AB  - Phomactins, natural products isolated from the culture broth of marine fungus
      Phoma sp., were found to be active as PAF antagonists. This unique carbon
      skeleton led us to investigate the structure-activity relationship demonstrating
      that the lipophilicity at C-(7-8), acetoxy, (methoxycarbonyl)oxy, and 3
      isoxazolyloxy substitution at C-20, and 2-beta-OH configuration at C-2 are all
      required for the enhancement of inhibitor activity.

PMID- 8978858
TI  - Elizabeth Baker Devereaux Lectureship--law and policy: signposts of change.

PMID- 8978859
TI  - Why the profession of occupational therapy will flourish in the 21st century. The
      1996 Eleanor Clarke Slagle Lecture.
AB  - The use of occupation as a therapeutic method is the essence of the profession of
      occupational therapy. This core of therapeutic occupation is flexible across
      cultures, times, health care environments, and different philosophies of the
      nature of the human being. Given this adaptability, the profession espouses
      diverse models of practice--the multiple frames of reference that guide
      therapeutic occupation for different populations in different settings. Across
      the history of the profession, therapeutic occupation has been the common core of
      otherwise different approaches to intervention. Although each of the many past
      and current models of practice has a different viewpoint, the common factor is
      the synthesis of occupational forms designed to elicit meaningful and purposeful
      occupational performance. Occupational synthesis is the essential act of the
      occupational therapist. It is necessary that occupational therapists confirm the
      power of therapeutic occupation through research that examines the profession's
      central principles. Occupational therapists are also urged to use the term
      occupation consistently and proudly in their interactions with recipients of
      therapy, fellow health care professionals, and each other. The profession of
      occupational therapy will flourish because occupation, its core, is so basic to
      human health yet so flexible, depending on the needs of the individual human
      being.

PMID- 8978860
TI  - The sensory profile: the performance of a national sample of children without
      disabilities.
AB  - OBJECTIVES: The purpose of this study was to obtain data about a national sample
      of children without disabilities on the 125-item revision of the Sensory Profile,
      a tool derived from sensory history items reported in the literature and designed
      to evaluate children's responses to commonly occurring sensory events. METHOD:
      Parents of 1,115 children completed the Sensory Profile. The children were 3 to
      10 years of age and did not have disabilities. Parents used a 5-point Likert
      scale to report the percentage of time their children engaged in each behavior.
      Researchers then analyzed the data, using multivariate methods to identify trends
      in performance and age and gender differences. RESULTS: Ninety-one (73%) of the
      profile's 125 items were found to be uncommon behaviors for this national sample
      of children without disabilities. Although age and gender differences were
      significant (p < .001), effect sizes were so small (i.e., below .2) that
      differences were not meaningful for clinical application (i.e., mean differences
      less than .5 points). Only two items in the visual category approached a 1-point
      difference when comparing younger and older children. CONCLUSION: There were no
      meaningful gender differences on the revised Sensory Profile, and only 2 items
      approached a meaningful difference related to age. Nearly three fourths of the
      items on the profile were uncommon for children without disabilities. If children
      with various disabilities display these behaviors, the Sensory Profile can be
      useful in evaluation and program planning for children with disabilities.

PMID- 8978861
TI  - Equivalence reliability of the functional independence measure for children
      (WeeFIM) administration methods.
AB  - OBJECTIVE: This study examined the equivalence reliability of two administration
      methods for the Functional Independence Measure for Children (WeeFIM). The two
      methods were direct observation of child performance and parental interview.
      METHOD: Thirty children between the ages of 19 months and 71 months with
      identified developmental disabilities were included in this study. The direct
      observation and interview methods were administered in random order to each
      subject within a 3-week period. The direct observation was completed in the
      educational setting, and the WeeFIM interview was obtained by either in-person
      interview or telephone interview with the parent. RESULTS: The intraclass
      correlation coefficient (ICC) for total WeeFIM ratings was .93, indicating
      consistency between the two administration methods. Analysis of the WeeFIM Motor
      (13 items) and Cognitive (5 items) domains yielded ICC values of .93 and .75,
      respectively, suggesting greater consistency for items measuring motor-related
      skills. CONCLUSION: The results demonstrate good agreement for total ratings when
      the WeeFIM is administered by direct observation and by interview with a parent.
      The findings establish the clinical usefulness of information collected by
      clinical interview.

PMID- 8978862
TI  - The use of environmental control units by occupational therapists in spinal cord
      injury and disease services.
AB  - OBJECTIVES: This study investigated issues related to the use of environmental
      control units (ECUs) with persons who have spinal cord injury and disease (SCI/D)
      to ascertain what, if any, changes are needed to optimize occupational therapy
      service delivery in this area. METHOD: A questionnaire was mailed to 120
      occupational therapists employed by facilities nationwide that serve person with
      SCI/D. The survey addressed the occupational therapist's role in the
      recommendation and use of ECUs, funding sources, and training needs. The response
      rate was 89% (n = 107). RESULTS: Most respondents (88%) indicated that
      occupational therapists were the predominant professionals in their facilities
      who evaluated and recommended ECUs. The majority of respondents (84%) reported
      using ECUs in hospital-based treatment with persons with SCI/D. However,
      respondents only recommended ECUs for home use for fewer than 25% of their
      clients. High cost and the lack of third-party reimbursement were the primary
      reasons that deterred respondents from recommending ECUs for home use. Fifty-five
      percent of the respondents reported a need for basic training and 86% for more in
      depth education and training in environmental control technologies. CONCLUSION:
      Outcomes data are needed to support the use of ECUs and to educate third-party
      payers about the benefits of ECUs for clients with quadriplegia in order to
      increase rates of reimbursement. In addition, occupational therapists themselves
      may need improved training in evaluating and training clients in the use of ECU
      technology.

PMID- 8978863
TI  - Anticipating retirement: the formation of narratives concerning an occupational
      transition.
AB  - OBJECTIVE: This study is the first part of a longitudinal investigation of the
      retirement process. This stage of the inquiry concerned how older persons
      anticipate their retirement. METHOD: Thirty-two workers were randomly selected
      from all workers age 63 years in a suburb of Stockholm. They participated in
      semistructured interviews about their work and their expectations for retirement.
      RESULTS: The participants narratives illustrated the complex work of interpreting
      the past and expected meaning in one's occupational life. The narratives, which
      anticipated widely different future trajectories, revealed many of the challenges
      and dilemmas of anticipating retirement and the close association of work
      experience to expectations for retirement. In particular, the narratives
      highlighted the participants' concerns about maintaining the quality of
      experience in activity. The findings also demonstrate the process by which
      persons anticipate and make choices about life change. CONCLUSIONS: People
      anticipate retirement through volitional narratives in which they link together
      past, present, and future. Understanding this volitional process of interpreting,
      anticipating, and making choices is important to understanding how people adapt
      to life changes.

PMID- 8978864
TI  - The model of functional deficits associated with hallucinations.
AB  - OBJECTIVES: The Model of Functional Deficits associated with hallucinations is
      used as part of the clinical documentation in the San Jose State University
      Psychosocial Occupational Therapy Clinic. On the basis of this model,
      hallucinations are classified according to functional deficits and whether the
      deficits are a result of the content or intrusiveness of the hallucinations. This
      classification is important because it helps occupational therapists know the
      full extent of the dysfunction through understanding the underlying pathology.
      The purpose of this classification is to assist in the development of clinical
      treatment plans that incorporate techniques for coping with hallucinations.
      METHOD: The sample included 39 clients seen in the clinic over a 4-year period.
      Student occupational therapists were responsible for documenting the
      classifications using the Model of Functional Deficits associated with
      hallucinations. The clients' charts were then reviewed retrospectively to
      classify the hallucinations according to the clients' functional deficits. The
      classification system ranged from Class 0, insufficient information, to Class VI,
      persistent hallucinations with profound functional deficits. With these
      classifications, interventions were planned with the clients in order for them to
      practice coping mechanisms (e.g., self-instruction, decreased stimulation,
      increased stimulation) to maintain function during their hallucinations. RESULTS:
      The findings indicated that 54% of the clients continued to experience
      hallucinations (i.e., Class II-Class V), although all received psychotropic
      medication, thus necessitating continuing therapeutic intervention. CONCLUSION:
      This model helps identify specific client experiences that can then be used to
      develop occupational therapy interventions.

PMID- 8978865
TI  - The impact of the classroom environment on defining function in school-based
      practice.
AB  - OBJECTIVE: Whether the environment is stressed in function-dysfunction decisions
      appears to depend on where in the hierarchy of components of complex tasks and of
      role skills the evaluating therapist is focused. This study examined the
      intervention planning decisions of occupational therapists who used the Model of
      Student Role Adaptation, which emphasizes the complex tasks involved in the
      student role. The purpose of the study was to determine whether these therapists
      were responding to environmental demands in planning their interventions. METHOD:
      Special education teachers selected tasks that they believed were the most
      essential for student functioning within their classroom environments. These
      selections were compared with the goals and objectives developed by occupational
      therapists who serve children in these settings. RESULTS: Chi square analysis
      indicated a significant relationship between tasks designated by the teacher
      participants as environmental demands and those included in occupational therapy
      intervention planning. CONCLUSION: The results suggest that the occupational
      therapist participants were responding to the environmental demands of the
      classroom when constructing their intervention plans.

PMID- 8978866
TI  - Developing a computer-based expert system for pediatric prosthetic training: a
      pilot project.

PMID- 8978867
TI  - Testing the value of a measurement protocol for DNA image cytometry and comparing
      different cytologic preparations.
AB  - OBJECTIVE: To analyze the influence of measuring parameters on the quality of DNA
      histograms, and to compare the results of DNA image cytometry (ICM) and flow
      cytometry (FCM). STUDY DESIGN: Material from 20 breast cancer cases was analyzed.
      The protocol for ICM analyzed (1) measuring system and image analysis parameters,
      (2) the quality of fixation, and (3) the presence of cytoplasm around nuclei. In
      Feulgen-stained slides (both fresh imprints and cytocentrifuge preparations) at
      least 200 nuclei were examined using a commercially available ICM system. DNA FCM
      on disaggregates was performed, also. RESULTS: Strict adherence to the protocol
      gave reliable DNA ploidy profile results. In contrast, deviations from the
      protocol gave very broad histograms. With the protocol, similar results were
      found for imprints and cytocentrifuge samples. Duplicate "blind" assessments were
      highly reproducible. DNA indices measured by FCM and ICM (on cytocentrifuge
      samples) correlated highly as well. CONCLUSION: With the protocol used, DNA
      ploidy profiles obtained by ICM from fresh imprints and cytocentrifuge
      disaggregate cell preparations were comparable.

PMID- 8978868
TI  - Non-small cell lung cancer. Morphology and DNA flow cytometry.
AB  - OBJECTIVE: To correlate stage-related and histologic features of non-small cell
      lung cancer (NSCLC) with DNA flow cytometric parameters. STUDY DESIGN: The
      clinicopathologic features, DNA flow cytometric parameters (ploidy type, S-phase
      fraction and DNA index [DI]) of 72 surgically resected NSCLC were reviewed.
      RESULTS: NSCLC were classified on the basis of their DI in diploid, peridiploid,
      hypotriploid, triploid, hypertriploid, tetraploid, hypertetraploid and multiploid
      tumors. DI was significantly related to pleural infiltration, pT, histologic type
      and evidence of necrosis. Tumors infiltrating the pleura were mostly triploid or
      hypertriploid; high pT stages were also hypertetraploid. Adenocarcinomas showed a
      wide DI distribution, squamous carcinomas were mostly diploid, triploid or
      hypertriploid and large cell carcinomas were mostly triploid, hypertriploid and
      hypertetraploid. The best combination of features able to predict disease relapse
      was pT plus pN plus grading and divergent differentiation. CONCLUSION: Many stage
      related and histologic features are associated with particular DI classes, which
      vary in relation to the feature itself and, in some cases, regardless of
      classical methods of grading and histologic typing. DNA content analysis
      highlights greater biologic heterogeneity in NSCLC than evidenced
      morphologically.

PMID- 8978869
TI  - Automated cell differentiation of bronchoalveolar lavage samples with two-step
      image analysis.
AB  - OBJECTIVE: To establish an easy method for performing an automated differential
      cell count on bronchoalveolar lavage (BAL) cytocentrifuge samples using
      morphometric parameters acquired by a digital image analyzer. STUDY DESIGN: The
      study population comprised 20 satisfactory cytocentrifuge preparations routinely
      processed in our laboratory. Images of at least 40 fields of interest were
      digitized and stored. The images were analyzed to assess the planimetric
      parameters. These were used for cell identification. Basic morphometric
      parameters were acquired by an automated image analysis procedure. The results
      obtained by this method are compared to those of the manual counting procedure.
      RESULTS: Following sequential analysis, computerized identification corresponded,
      in > 97% of the cells, to the results of manual cell typing. After data analysis,
      < 1% of cells remained unidentifiable. CONCLUSION: Although the number of
      specimens evaluated is not yet large enough to allow a definitive statement, the
      use of image analysis systems seems a promising approach in automated
      differential cell counting in BAL preparations.

PMID- 8978871
TI  - Morphometry in histopathology. An image analysis workstation for the pathology
      laboratory.
AB  - OBJECTIVE: To investigate the value of morphometry in comparative histologic
      analysis of diseases, fixing a set of parameters suitable for analysis and to
      create a general strategy for data storage and economical data management. STUDY
      DESIGN: To establish the following fundamental principles for morphometric
      measurements: (1) linear measurements to determine the distance between two
      points by using an eyepiece graticule with an engraved scale or alternatively
      with a ruler on a projected microscopic image or photograph; (2) Stereology based
      on geometric probability, allowing features in three dimensions to be measured
      from two-dimensional images; and (3) a computerized image processing and analysis
      system for image capture, storage and analysis using specialized software and
      hardware. RESULTS: Measurement procedures were demonstrated in different
      parameters using regenerative nodules of alcoholic cirrhosis as a model.
      Comparative analysis between primary biliary cirrhosis, alcoholic cirrhosis,
      posthepatitic cirrhosis and hepatocellular carcinoma showed the highest
      regenerative activity in posthepatitic cirrhosis. CONCLUSION: With current
      advances in computer technology, rapid, automatic measurements can be made from
      tissue sections and a variety of practical applications for the pathology
      laboratory, such as nuclear morphometry for comparison of different kinds of
      liver diseases, including classification of hepatocellular carcinoma.

PMID- 8978870
TI  - Evaluation of prostatic intraepithelial neoplasia after treatment with a 5-alpha
      reductase inhibitor (finasteride). A methodologic approach.
AB  - OBJECTIVE: To develop a methodology applicable to the morphologic study of the
      efficacy of finasteride on prostatic intraepithelial neoplasia (PIN), a putative
      precursor of prostate cancer. STUDY DESIGN: Three PIN foci were reviewed in two
      simple prostatectomy specimens from patients with clinical diagnoses of benign
      prostatic hyperplasia and treated with finasteride for six months. The
      feasibility of PIN diagnosis and grading based on "diagnostic distance" was
      investigated. It is a measure of the "extent" to which the observed features are
      different from those of the untreated prototypes representing the following
      diagnostic categories: normal prostate, low and high grade PIN and prostatic
      adenocarcinoma with a cribriform or large acinar pattern. Uncertainty in the PIN
      diagnosis and grading was dealt with by means of a Bayesian belief network (BBN).
      RESULTS: The distance measure values of the three PIN foci from the prototype of
      untreated, nonneoplastic prostate were 9, 7 and 8, respectively, in relative,
      arbitrary units. Their distance from the two prostate cancer patterns (large
      acinar and cribriform) was as high as 8-10. The distance of these foci from
      either low or high grade PIN were as low as 5, 3 and 2, and 3, 5 and 4,
      respectively. BBN produced the highest belief values for PIN, thus confirming the
      morphology-based and diagnostic distance-supported diagnosis; however, the belief
      values were low for both grades. CONCLUSION: The results provided by BBN analyses
      and diagnostic distance measures support the conclusion that this methodology is
      applicable to assessing the efficacy of finasteride treatment of PIN.

PMID- 8978872
TI  - Breast carcinoma. Correlations between visual diagnostic criteria for histologic
      grading and features of image analysis.
AB  - OBJECTIVE: To investigate the relevance of image analysis for grading breast
      carcinomas. STUDY DESIGN: The results of histologic grading were correlated with
      18 features of image analysis, including SD. "Simple" characteristics, like area
      and perimeter, shape indices, optical density and textural features of nuclei
      from cancer cells, were analyzed. Hematoxylin-eosin-stained tissue sections of 67
      cancer specimens were routinely used for the study. RESULTS: We found
      statistically significant correlations between overall histologic grading and the
      sum of its subscores and features of image analysis, especially nuclear area,
      nuclear perimeter and the diameter of the circumscribing circle (diametercirc),
      including their SDs. The visually and therefore subjectively assessed subscore of
      the nuclear pleomorphism of histologic grading significantly correlated with the
      features of image analysis, like nuclear area, nuclear perimeter, diametercirc,
      integrated optical density and correlation (and their SDs). There were
      significant relationships between the absolute numbers of mitoses per 10 high
      power fields and nuclear area, nuclear perimeter and diametercirc (and their
      SDs). We did not observe a significant correlation between the subscore of tubule
      formation of histologic grading and any of the features of the image analysis
      studied. Furthermore, the correlations between the features of image analysis and
      the subscores of the visual histologic grading system were analyzed with respect
      to each other. The subscore of nuclear pleomorphism of histologic grading
      correlated best with overall grading (r = .72), whereas no significant
      correlation could be found between the subscores of nuclear pleomorphism and
      mitotic activity. CONCLUSION: Image analysis provides objectivity and
      reproducibility to the grading of breast carcinomas and thus could contribute to
      more individualized prognostication of the disease.

PMID- 8978873
TI  - Potential of the back propagation neural network in the morphologic examination
      of thyroid lesions.
AB  - OBJECTIVE: To investigate the potential of back propagation (BP) neural networks
      (NNs) in the discrimination of benign from malignant thyroid lesions. STUDY
      DESIGN: The study was performed on May-Grunwald-Giemsa-stained smears obtained by
      fine needle aspiration (FNA). Using a custom image analysis system, 26 features
      that describe the size, shape and texture of the nucleus were measured from each
      cell. The cases were distributed according to categories, as follows: 25 cases of
      goiter and follicular adenomas, 1 case of follicular carcinoma, 12 cases of
      papillary carcinoma, 6 cases of oncocytic adenoma, 3 cases of oncocytic carcinoma
      and 4 cases of Hashimoto thyroiditis. From each case about 100 nuclei were
      measured; they formed a pool of 13,850 feature vectors. Out of this pool, 2,770
      vectors were randomly selected to form the training set, and the remaining 11,080
      vectors formed the test set. RESULTS: The application of a BP NN on the nuclear
      measurements permitted correct classification of 90.61% nuclei. Classification at
      the patient level was performed using a hypothesis test for proportion and two
      different hypothesis values, one equal to the overall accuracy of the NN and one
      equal to 50%. The second method permitted correct classification of 98% of
      patients. CONCLUSION: These results indicate that the use of NNs combined with
      image morphometry and statistical techniques may offer useful information on the
      potential malignancy of thyroid cells and may improve the diagnostic accuracy of
      FNA of the thyroid gland, especially in cases classified as suspicious for
      malignancy.

PMID- 8978874
TI  - Late occurrence of K-ras gene mutations in the pathogenesis of squamous cell
      carcinoma of the lung: analysis in sputum.

PMID- 8978875
TI  - Prevention activities at the National Institutes of Health.

PMID- 8978876
TI  - Smoking among black and white youth: differences that matter.

PMID- 8978877
TI  - Trends in cigarette smoking among children in a southern community, 1976-1994:
      the Bogalusa Heart Study.
AB  - Cigarette smoking among adolescents continues to be a major public health problem
      in the United States. Smoking trends from 1976-1977 to 1992-1994 were examined in
      the Bogalusa Heart Study, an investigation of cardiovascular disease risk factors
      among black and white, male and female adolescents in a semirural town in the
      southern United States. Age-race-sex specific chi 2 tests for trends over five
      survey periods were conducted. In almost every age group, black boys and girls
      were less likely to be current smokers or to have ever smoked or tried
      cigarettes, as compared with white boys and girls, respectively (P < 0.01).
      Within age groups, few significant trends in smoking status from 1976-1977
      through 1992-1994 were observed among white boys and girls. Among black males and
      females, however, sharp decreases were observed among all age groups in the
      prevalence of having ever smoked or tried cigarettes (P = 0.0001) and among the
      older age groups in the prevalence of being a current smoker (P = 0.0001). Thus,
      substantial declines in the prevalence of smoking were observed among black
      children but not among white children. Further research is required to understand
      why these ethnic differences in smoking occurred so that public health programs
      may target further the smoking behaviors in children.

PMID- 8978878
TI  - Response error in self-reported current smoking frequency by black and white
      established smokers.
AB  - As compared with white smokers, black smokers, although they report using fewer
      cigarettes per day, are at higher risk for most smoking-related diseases. Among
      black smokers serum cotinine levels are also higher in proportion to cigarettes
      per day; this observation has led to suggestions of bias in self-reporting. The
      purpose of this study was to evaluate and compare the extent of errors in self
      reported smoking patterns among black and white established smokers. Ninety-seven
      white and 66 black smokers participated in structured telephone interviews,
      filled out two self-administered questionnaires one week apart, and collected all
      of their cigarette butts for a week. Group differences in the validity of self
      reported smoking patterns were assessed by comparison with cigarette butt counts
      and the measured butt lengths. Both black and white smokers significantly
      overestimated smoking on our measure of smoking frequency (both P < 0.001); the
      group difference in bias was not significant (P = 0.13). There was no evidence
      that underreporting was more common among blacks than among whites (P = 0.67).
      Test-retest reliability was not significantly different in the two groups (P =
      0.09). Both groups performed poorly when asked to categorize their smoking
      frequency according to the cutpoints of the Fagerstrom Test for Nicotine
      Dependence. Black smokers smoked more of each cigarette and smoked longer
      cigarettes, but they smoked fewer total millimeters of cigarettes per day (all P
      < 0.001). Contrary to an earlier report, the disproportionately high cotinine
      levels could not be attributed to reporting error.

PMID- 8978879
TI  - Cardiovascular risk factors and hyperinsulinemia in elderly men: the Honolulu
      Heart Program.
AB  - Associations of cardiovascular risk factors, including several measures of
      adiposity, with hyperinsulinemia were assessed in 3562 elderly (71 to 93 years of
      age) Japanese American men from the Honolulu Heart Program who were examined
      between 1991 and 1993. In addition, cardiovascular risk factors measured 25 years
      earlier were also examined in relation to hyperinsulinemia. Hyperinsulinemia was
      defined as fasting insulin > or = 95th percentile (20 microU/mL) among the subset
      of subjects (n = 504) who were nonobese and free of clinical diabetes and glucose
      intolerance. When this definition was applied to the entire population, the
      prevalence of hyperinsulinemia declined cross-sectionally with age (P < 0.001)
      from 24.2% in men aged 71 to 74 years to 16.4% in men aged 85 to 93 years.
      Factors having a positive and independent association with hyperinsulinemia
      included body mass index (BMI), triglycerides, glucose, hematocrit, use of
      diabetic medication, heart rate, and hypertension. The association with physical
      activity was negative. Triglycerides, BMI, diabetic medication, hypertension, and
      smoking levels measured 25 years earlier were also associated independently with
      hyperinsulinemia. Associations were similar in nondiabetic subjects. Three
      measures of adiposity (BMI, waist circumference, and subscapular skinfold
      thickness) were independently related to hyperinsulinemia cross-sectionally.
      However, associations involving a difference between the 80th and 20th
      percentiles in each adiposity measure appeared strongest for BMI (odds ratio (OR)
      = 4.5, 95% confidence interval (CI) = 3.7 to 5.6) and waist circumference (OR =
      4.1, 95% CI = 3.3-5.1) and slightly weaker for subscapular skinfold thickness (OR
      = 2.1, 95% CI = 1.8-2.5). These findings suggest that features of an insulin
      resistance syndrome including dyslipidemia, glucose intolerance, hypertension,
      and obesity, assessed both cross-sectionally and 25 years previously, are
      associated independently with hyperinsulinemia in elderly Japanese American men.

PMID- 8978880
TI  - The effect of nonresponse on prevalence estimates for a referent population:
      insights from a population-based cohort study. Atherosclerosis Risk in
      Communities (ARIC) Study Investigators.
AB  - Characterization of nonrespondents, with the aim of detecting nonresponse bias,
      is a crucial component of prospective studies. This study was undertaken to
      investigate the demographic and health characteristics of nonrespondents to a
      population-based cohort study of cardiovascular disease, to determine whether
      early-stage nonrespondents differ from late-stage nonrespondents, and to estimate
      the bias in prevalence estimates for the source population. Sixty-seven percent
      of eligible subjects completed all phases of the cohort recruitment. Compared to
      respondents, nonrespondents were less likely to be married, less likely to be
      employed, and less likely to be well educated. Nonrespondents tended to describe
      their general health in less favorable terms and were more likely to be smokers.
      Their reported disease profile, however, was not dissimilar to that of
      respondents. For several demographic and health characteristics, including
      marital status, education, and smoking, early-stage nonrespondents differed from
      respondents more than did late-stage nonrespondents. For example, 42% of early
      nonrespondents were smokers compared to 37% of late nonrespondents and 22% of
      respondents. Overall, the bias in prevalence estimates related to nonresponse was
      small (< 5%) for most of the measured characteristics. Although nonresponse to
      health surveys is associated with typical attributes, early nonrespondents differ
      from respondents more than do late-stage nonrespondents. With few exceptions,
      however, a 33% nonresponse rate did not appear to introduce substantial bias into
      prevalence estimates for the source community.

PMID- 8978881
TI  - The Women's Health Trial Feasibility Study in Minority Populations: design and
      baseline descriptions.
AB  - The Women's Health Trial: Feasibility Study in Minority Populations (WHT:FSMP), a
      randomized trial of 2208 women, was conducted to investigate three questions.
      First, can women from minority and low-socioeconomic-status populations be
      recruited in numbers sufficient to evaluate a dietary intervention designed to
      lower fat intake. Second, the efficacy of a low fat, increased fruit/vegetable/
      grain product intervention for reducing fat consumption. Third, will
      participation in the intervention lower plasma cholesterol and estradiol levels
      relative to the controls. The baseline results showed that an adequate number of
      minority and low SES women could be recruited to test the study hypotheses. A
      diverse study population of postmenopausal women consuming a high fat diet was
      recruited: 28% of participants were Black, 16% were Hispanic, 11% had less than a
      high school level of education, and 15.5% had household incomes of < $15,000.

PMID- 8978882
TI  - The HERITAGE Family Study: quality assurance and quality control.
AB  - The HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) Family Study
      is the first multicenter family clinical trial of its kind. Conducted by a
      consortium of five universities in the United States and Canada, the study has as
      its primary goal to document the role of the genotype in the cardiovascular,
      metabolic, and hormonal responses to aerobic exercise training. A comprehensive
      protocol was implemented at four Clinical Centers (CC) for the generation of data
      on sedentary subjects. This group included 450 caucasians from 90 nuclear
      families (father, mother, three children) and 200 black subjects from 40 to 100
      family units over a 5-year period. The entire family was tested before and after
      a 20-week exercise training program. The fifth participating center, the Data
      Coordinating Center (DCC), is responsible for data management and data analysis.
      A Consortium Coordinating Center (CCC) responsible for the overall coordination
      and direction of the study was established at the Quebec CC. Quality assurance
      and quality control are jointly coordinated by the CCC and the DCC. A multicenter
      study of this magnitude requires careful standardization of all procedures and
      constant monitoring of quality control at all levels of operation. This report
      describes the quality assurance and quality control measures implemented in the
      HERITAGE Family Study, including some examples with real data.

PMID- 8978906
TI  - Genetic characterization of equine apolipoprotein A-I using isoelectric focusing.

PMID- 8978883
TI  - A case-control study of prosthetic implants and selected chronic diseases.
AB  - We examined the association between prosthetic nonbreast implants and selected
      malignant neoplasms, connective tissue disorders, and neurologic diseases. We
      conducted a case-control study from an insurance claims database. We selected
      controls who had diseases for which no association with implants have been
      claimed or reported. Data were analyzed using both tabular and polytomous
      regression analysis methods, including methods to account for the large number of
      comparisons. All analyses exhibited positive associations between implants (both
      silicone and metal) and neurologic conditions, especially idiopathic progressive
      neuropathy and Meniere syndrome, as well as the expected associations with
      arthritic conditions. There also was an unexpected negative association between
      metal implants and brain tumors. In conclusion, further studies of prosthetic
      implants and neurologic diseases appear warranted. These studies should obtain
      medical histories to control for possible confounding effects of drug treatments
      associated with implant surgery.

PMID- 8978907
TI  - Duplication of the Ace.1 locus in Culex pipiens mosquitoes from the Caribbean.
AB  - In Culex pipiens mosquitoes, AChE1 encoded by the locus Ace.1 is the target of
      organophosphorus and carbamate insecticides. In several resistant strains
      homozygous for Ace.1RR, insensitive AChE1 is exclusively found. An unusual
      situation occurs in two Caribbean resistant strains where each mosquito, at each
      generation, displays a mixture of sensitive and insensitive AChE1. These
      mosquitoes are not heterozygotes, Ace.1RS, as preimaginal mortalities cannot
      account for the lethality of both homozygous classes. This situation is best
      explained by the existence of two Ace.1 loci, coding, respectively, a sensitive
      and an insensitive AChE1. Thus, we suggest that in the Caribbean a duplication of
      the Ace.1 locus occurred before the appearance of insecticide resistance at one
      of the two copies.

PMID- 8978908
TI  - Inheritance and linkage of aspartate aminotransferase in Anopheles stephensi.

PMID- 8978909
TI  - Identification of a cDNA encoding 6-phosphogluconate dehydrogenase from a human
      heart cDNA library.
AB  - A full-length cDNA clone for human 6-phosphogluconate dehydrogenase (PGD) was
      isolated from a human adult heart cDNA library. The clone encoded an open reading
      frame of 483 amino acids. When the amino acid sequences of human PGD and sheep
      PGD were aligned, 94.2% identity between these two proteins was found. Its
      calculated molecular weight is 53,149 daltons. The predicted isoelectric point is
      6.85. When the secondary structure of human PGD was examined by the PROSIS
      software, 36% alpha-helix and 9% beta-sheet were found.

PMID- 8978910
TI  - Inheritance and linkage analysis of ten enzyme and blood protein loci in the
      Japanese brown frog Rana japonica.
AB  - In order to clarify the genetic linkage groups of the Japanese brown frog Rana
      japonica, and compare them with those of other vertebrates, the inheritance of 10
      enzyme and blood protein loci was examined in 267 offspring derived from 18
      crosses using 10 males heterozygous at these loci. Most of the segregation tests
      exhibited no significant deviations from the expected normal Mendelian ratios. Of
      32 pairs of loci tested for linkage, 29 pairs showed independent assortment in
      all crosses examined. In the three other locus pairs, between ADH-1 and Alb, IDH
      1 and Hb-1, and LDH-B and MPI, all offspring analyzed were parental, and there
      were no recombinants. These three linkage groups comprising six loci were thus
      established in R. japonica, whereas no linkage between the other four loci, AAT
      1, ADA, GPI, and PEP-A, was observed.

PMID- 8978913
TI  - Glossary of molecular biology terminology.

PMID- 8978912
TI  - Tapping the potential of government-industry collaboration.

PMID- 8978914
TI  - Editorial summary of the Pre-symposium workshop on the Contemporary Assessment of
      Technologies.
AB  - The following is the editor's summary of the Pre-symposium workshop on
      Contemporary Assessment of Technologies presented at the Symposium on Molecular
      Approaches to Laboratory Diagnosis at San Francisco in February 1995. This
      workshop was moderated by Dr Joel M. Palefsky, and Dr Michael P. Busch. We have
      briefly summarized the presentations by: (1) Dr Indira Hewlett of the Center for
      Biologics Evaluation and Research, Food and Drug Administration entitled
      'Technology overview'; (2) Dr John J. Sninsky of Roche Molecular Systems Inc.
      entitled "Polymerase Chain Reaction'; (3) Dr Terrance Walker of Becton Dickinson
      Research Center entitled 'Strand Displacement Amplification'; (4) Dr Mickey Urdea
      of Chiron Corporation entitled 'bDNA assay' and (5) Dr Robert H. Singer of
      University of Massachussetts Medical Center entitled 'Image analysis of in situ
      hybridization'. Although it was not possible to list all the references to the
      primary literature, we have attempted to provide the key references as far as
      possible.

PMID- 8978911
TI  - Plasma protease inhibitor (PI) system in the laboratory opossum, Monodelphis
      domestica.
AB  - Protease inhibitor (PI) polymorphism was observed in the laboratory opossum,
      Monodelphis domestica, by either one-dimensional acid polyacrylamide gel
      electrophoresis (PAGE; pH 4.6) or isoelectric focusing (pH 3.5-5.0) followed by
      immunoblotting with rabbit antiserum to human alpha 1-antitrypsin; but acid PAGE
      produced superior resolution of the PI proteins. Family studies demonstrated an
      inheritance of nine codominant autosomal alleles, PID, PIE, PIF, PIG, PIH, PII,
      PIJ, PIK, and PIM, and a population study revealed frequencies of 0.411, 0.010,
      0.341, 0.034, 0.023, 0.071, 0.035, 0.020, and 0.055, respectively.

PMID- 8978915
TI  - Probes in DNA/RNA hybridization.

PMID- 8978916
TI  - Cytogenetic and molecular detection of genetic mutations in human tumours.

PMID- 8978917
TI  - Molecular diagnosis of microbial infections.

PMID- 8978918
TI  - Ligase chain reaction.

PMID- 8978919
TI  - Applications of molecular biology to analyses of forensic evidence.

PMID- 8978920
TI  - Parasitic infections--molecular diagnosis and rational drug design.

PMID- 8978921
TI  - Monkey neurovirulence test for live mumps vaccine.

PMID- 8978922
TI  - Establishment and characterization of Japanese B encephalitis virus persistent
      infection in the Sf9 insect cell line.
AB  - The Sf9 cell line, commonly used for gene expression by recombinant
      baculoviruses, can be productively infected by Japanese B encephalitis virus
      (JEV). Two wild-type JEV strains (P3 and SA14) caused a cytopathic effect (CPE)
      in the Sf9 cells, while no apparent CPE was caused by an attenuated strain (SA14
      14-2). The JEV viral antigens were expressed in the infected Sf9 cells and
      intracellular virus particles were found by electron microscopy as a result of
      infection with all three strains. Titres of cell-associated and cell-free
      supernatant virus remained stable for relatively long periods of cultivation,
      suggesting that both wild-type and attenuated JEV strains established productive
      and persistent infections of Sf9 cells. The JEV produced by the Sf9 cells could
      be neutralized by anti-JEV reference serum, but relatively smaller plaques were
      formed in BHK21 cells infected with JEV that had been cultivated long term in Sf9
      cells. This system for virus propagation has a number of potentially important
      uses for enhancing progress in JEV study and control.

PMID- 8978923
TI  - Analysis of the antibody response in humans with a new inactivated hepatitis A
      vaccine.
AB  - Sera from subjects vaccinated with the Pasteur Merieux (PM) inactivated hepatitis
      A vaccine (AVAXIM) have been analysed in order: (1) to assess comparability of
      the results provided by a modified radio-immunoassay (mRIA) in the different
      laboratories involved in testings of sera during clinical trials and by enzyme
      linked immunoabsorbent assay (ELISA) used during development of other inactivated
      hepatitis A vaccines; (2) to describe the IgM responses elicited by this vaccine
      compared with one control vaccine [HAVRIX, 720 ELISA antigens units; Smithkline
      Beecham (SB), Rixensart, Belgium]; (3) to provide comparative data between the PM
      vaccine and the SB vaccine on neutralizing activities of vaccine-induced
      antibodies. Vaccine-induced antibody titres evaluated by a mRIA in different
      laboratories correlated well and validated the comparability of the results
      obtained in various vaccine trials conducted by PM. Geometric mean titres (GMTs)
      expressed as milli-international units (mlU/ml) were higher with ELISA especially
      after the first dose, but seroconversion rates were similar and a good
      correlation was found between the two assays. IgM vaccine-induced antibodies were
      detectable in nearly all vaccinated subjects from week 2 after vaccination, with
      a peak titre between weeks 2 and 4 after the first dose. Comparison of GMTs by
      the Student Fisher t-test was statistically significant (P < 0.05) only at week 2
      with higher titres in PM vaccinees. Neutralizing antibodies were detected after
      vaccination with the PM inactivated hepatitis A vaccine. The titres gradually
      increased between the second week after the first dose and the booster dose (week
      24). A strong booster effect of the second dose on neutralizing titres was
      observed. Seroneutralizing titres induced at week 2 in subjects vaccinated with
      the PM inactivated hepatitis A vaccine were statistically significantly higher (P
      < 0.05) from those induced by the SB vaccine.

PMID- 8978924
TI  - A validatible porosimetric technique for verifying the integrity of virus
      retentive membranes.
AB  - The verification of membrane integrity for filtration processes specifically
      designed for the removal of adventitious virus from biotherapeutics is of the
      utmost importance to both biomanufacturers and regulatory agencies. Although
      conventional bubble-point and air-diffusion tests are widely accepted for
      integrity testing of bacteria-retentive membranes, these tests have severe
      limitations in their ability to assess the integrity of virus-retentive
      membranes. A novel membrane integrity test based upon liquid-liquid porosimetric
      principles (CorrTest) has been specifically designed to correlate and predict the
      virus retention capabilities of Viresolve virus removing membranes. To optimize
      test sensitivity for both Viresolve/70 and Viresolve/180 membrane types, two
      distinct porosimetric correlations at different transmembrane pressures have been
      developed. Based upon an 80% prediction interval, an integrity test performed at
      either test pressure can reliably predict the ability of Viresolve membranes to
      remove the bacteriophage phi X174 to within 0.4 log removal value (LRV) units. To
      maintain test sensitivity and provide greater flexibility for conducting the
      liquid-liquid intrusion integrity test, appropriate pressure- and temperature
      correction equations have been established. The two immiscible fluids employed in
      the developed technology are easily flushed from the membrane structure and are
      generally regarded as acceptable, non-toxic reagents for pharmaceutical
      applications. Consequently, the CorrTest integrity test can reliably and non
      destructively measure both pre- and post-use membrane integrity to verify virus
      removal performance with the Viresolve module.

PMID- 8978925
TI  - Validation of peptide mapping for protein identity and genetic stability.
      Biologics and biotechnology section, pharmaceutical research and manufacturers of
      America.

PMID- 8978926
TI  - Creutzfeldt-Jakob disease: current U.S. policy to further reduce the possible
      risk of transmission by transfusion.
AB  - Because the results of epidemiological and subhuman primate studies conducted
      over the last quarter of a century have failed to show a statistically
      significant risk of transmission of CJD by transfusion of blood components or
      plasma derivatives, the FDA's position is that only a theoretical low risk of CJD
      transmission cannot be excluded at this time. Consequently, FDA issued two
      memoranda on 8 August 1995 as updated interim policy documents recommending: (1)
      permanent deferral from donating blood or plasma for all persons who state at the
      time of donation, or for whom post donation information becomes available, that
      they have ever received pit-hGh, a dura mater transplant graft, or have a blood
      relative history of CJD, unless this increased risk for CJD is excluded on the
      basis of genetic analysis testing; (2) the quarantining of all undistributed in
      date units of blood or blood components collected from either of these three
      groups of donors together with notification of all consignees of such in-date
      units so that distributed units also can be quarantined and recipient tracing and
      notification may be effected, and (3) the withdrawal from distribution and
      quarantining of in-date plasma derivative products derived from plasma pools
      containing a unit from either of these three groups of donors at known high risk
      for CJD, or donors subsequently diagnosed as having CJD. Consignees of these
      products are to be notified in order that they, in turn, may inform physicians or
      other qualified personnel responsible for the care of product recipients to
      provide counseling as deemed medically appropriate. The 'family history of CJD'
      criterion was further clarified to mean a 'history of CJD in 2 or more family
      members' during the BPAC meeting of 14 December 1995. In a workshop meeting on 29
      January 1996 the FDA urged that additional laboratory animal data be generated by
      plasma derivative manufacturers in order to ascertain if the sterilization steps
      used in their production of plasma derivatives further reduce the risk of
      transmission of CJD.

PMID- 8978927
TI  - Nanofiltration of immunoglobulin with 35-nm filters fails to remove substantial
      amounts of HCV.

PMID- 8978928
TI  - Reverse transcriptase activity in vaccines derived from chick cells.

PMID- 8978929
TI  - Further studies on the suppression of luteinizing hormone release due to
      activation of medial preoptic-anterior hypothalamic area mu-opioid receptors.
AB  - Our laboratory has previously demonstrated that specific activation of mu-opioid
      receptors in the medial preoptic-anterior hypothalamic area with [D-Ala2, N Me
      Phe4, Gly-ol5]-enkephalin (DAGO) suppresses luteinizing hormone secretion in the
      ovariectomized rat [29]. In the present study, three experiments were undertaken
      to ascertain whether changes in the activity of norepinephrine or dopamine
      neurons modulate the decrease in luteinizing hormone release in response to DAGO.
      The first experiment utilized push-pull perfusion in conjunction with HPLC to
      assess in vivo norepinephrine release in the medial preoptic-anterior
      hypothalamic area in response to perfusion of this site with DAGO (5
      micrograms/h). DAGO significantly decreased luteinizing hormone release, but
      perfusate norepinephrine levels did not change. In the second experiment, push
      pull perfusion in the medial preoptic-anterior hypothalamic area with
      cerebrospinal fluid (CSF) or CSF containing DAGO was done in rats pretreated with
      the norepinephrine synthesis inhibitor, FLA-63. This drug pretreatment had no
      effect on the DAGO-induced suppression of luteinizing hormone secretion. In
      experiment 3, push-pull perfusion in the medial preoptic-anterior hypothalamic
      area with CSF followed by CSF containing DAGO was done in rats pretreated with
      vehicle, or a dopamine receptor antagonist, either pimozide or d-butaclamol.
      Neither dopamine receptor antagonist had any effect on the DAGO-induced
      suppression of luteinizing hormone release. Thus, these studies do not support a
      role for alterations in the activity of norepinephrine or dopamine neurons in
      mediating the suppression of luteinizing hormone release in response to
      activation of mu-opioid receptors in the medial preoptic-anterior hypothalamic
      area in the ovariectomized rat.

PMID- 8978930
TI  - Glial tubes in the rostral migratory stream of the adult rat.
AB  - In the central nervous system cell migration is usually restricted to
      developmental periods and occurs mainly radially, following the radial glia.
      Nevertheless, in the subependymal layer of the adult rodent forebrain tangential
      migration of newly generated neuronal precursors directed to the olfactory bulb,
      which follow a well-defined pathway without dispersion, has been recently
      demonstrated. In the present study, by using light microscopic
      immunocytochemistry for glia-associated antigens (glial fibrillary acidic
      protein, S-100 and vimentin), and conventional electron microscopy, we observed a
      dense mesh-work of astrocytic cells and processes throughout the subependymal
      layer of the adult rat. These cells were organized to form tangentially oriented
      glial tubes in the subependymal layer of the lateral ventricle and in its rostral
      extension to the olfactory bulb. Glial tubes were particularly evident within the
      rostral extension and were widely intercommunicating. Using markers for the
      proliferating/ migrating cells of the rostral migratory stream (5-bromo-2'
      deoxyuridine, PSA-NCAM, class III beta-tubulin), we provide evidence that long
      chains of PSA-NCAM/beta-tubulin-positive, newly generated cells are consistently
      observed inside the glial tubes. These results demonstrate the existence of a
      peculiar glial organization within the subependymal layer of the adult rat,
      consisting of long astrocytic tubes that likely represent a new type of glial
      guidance, accounting for the tangential migration of a high number of cells along
      their restricted pathway, to the olfactory bulb.

PMID- 8978931
TI  - Supramammillary neural discharge patterns and hippocampal EEG.
AB  - Rhythmic multiunit activity, leading the negative peak of concurrently recorded
      dentate rhythmical slow-wave activity (RSA, theta) by a constant degree over a
      range of RSA frequencies, was observed in the supramammillary nucleus (SuM) after
      carbachol infusion (5%, 0.25-0.5 microliter) into the nucleus pontis oralis
      (RPO). As the rhythmic SuM activity survived bilateral transection anterior to
      SuM, its occurrence is not dependent on descending influences from the septum or
      hippocampus. Infusion of additional carbachol into the RPO resulted in
      epileptiform "sharp-waves" in the hippocampal EEG, and correlated nonrhythmic
      cell discharge in the SuM. Bilateral transection rostral to SuM abolished the
      sharp-wave related SuM activity (and restored SuM rhythmical activity). Thus, in
      contrast to RSA related rhythmical SuM discharge, sharp-wave related SuM
      discharge seems dependent on descending projections from the hippocampus.

PMID- 8978932
TI  - GABAergic neurons in mammalian thalamus: a marker of thalamic complexity?
AB  - The present study evaluated the occurrence, distribution, and number of GABAergic
      neurons in the thalamus of different mammalian species (bat, mouse, rat, guinea
      pig, rabbit, cat, monkey, humans), by means of light microscopical
      immunoenzymatic localization of GABA or of its biosynthetic enzyme glutamic acid
      decarboxylase and by ultrastructural immunogold detection of GABA. Our data
      demonstrated that: 1) GABAergic local circuit neurons were detected in the
      thalamic visual domain in all the species analyzed, whereas in other thalamic
      nuclei their presence and number varied among species; 2) the number of GABAergic
      local circuit neurons progressively increased in the dorsal thalamus of species
      with more complex behavior; 3) the presence of local circuit neurons conferred a
      similar intrinsic organization to the dorsal thalamic nuclei, characterized by
      complex synaptic arrangements; 4) in the reticular thalamic nucleus, whose
      neurons were GABA-immunoreactive in all the examined species, the cellular
      density decreased from the bat to humans. These findings strongly suggest that
      thalamic GABAergic local circuit neurons are not directly related to the ability
      to perform specific sensorimotor tasks, but they are likely to reflect an
      increasing complexity of the local information processing that occurs at thalamic
      level.

PMID- 8978933
TI  - GAP-43 mRNA and calcitonin gene-related peptide mRNA expression in sensory
      neurons are increased following sympathectomy.
AB  - Sympathectomy has been shown to result in an increased density of fibers
      immunoreactive for sensory peptides in peripheral targets innervated by both
      sensory and sympathetic neurons, providing evidence for functional interactions
      between sympathetic and sensory systems. These findings provided the background
      for examining the hypothesis that axonal outgrowth is induced from sensory
      neurons following sympathectomy. We examined the expression of GAP-43 mRNA, a
      specific marker for axonal outgrowth, in cervical (C3, C7, C8) and thoracic (T1,
      T2) dorsal root ganglia (DRG) of the rat following bilateral removal of the
      superior cervical ganglion, to assess whether the described increases in
      peptidergic afferent fibers reflected axonal outgrowth. In situ hybridization was
      used with 35S labeled riboprobes complementary to GAP-43 mRNA, and to calcitonin
      gene-related peptide (CGRP) mRNA, a marker for a major subset of thin-fiber
      sensory neurons. The density of GAP-43 mRNA nearly doubled by 18 h following
      sympathectomy and reached a threefold increase by 3 days. By 45 days following
      surgery, the GAP-43 mRNA level was still nearly twice that of normal animals,
      CGRP immunoreactivity was also examined: the density of fibers in the iris and
      cornea of sympathectomized animals was considerably greater from two weeks to 45
      days following surgery, than in sham-operated controls. Concomitantly, there was
      a slight but significant increase in CGRP mRNA expression in T1 and C3 DRG 14
      days postsympathectomy. Quantitative computerized image analysis demonstrated
      that GAP 43 mRNA expression in sympathectomized animals was 1.5 times greater in
      medium-sized DRG neurons and almost fourfold greater in small DRG neurons than in
      control rats. These results indicate that sympathetic denervation elicits axonal
      outgrowth in the population of sensory neurons that give rise to the small
      unmyelinated and thinly myelinated axons of peripheral nerves.

PMID- 8978934
TI  - Role of different subtypes of adrenoceptors in pressor responses to
      catecholamines released from sympathetic nerve endings.
AB  - The role of alpha 1- and alpha 2-adrenoceptors in the vascular effects of
      catecholamines, either released locally from sympathetic nerve endings (e.g., in
      vascular smooth muscle) or derived from the adrenal medulla or administered
      intravenously, was studied using selective antagonists of these adrenoceptors.
      The ganglionic stimulant dimethylphenyl-piperazinium-iodide (DMPP) exerted dual
      actions on blood pressure: a rapid and short-term pressor reaction (phase I)
      resulting from catecholamine release elicited by ganglion stimulation, followed
      by a more sustained blood pressure elevation (phase II) resulting from the
      circulating catecholamines released from the adrenal medulla. The selective alpha
      2-adrenoceptor, but a not subtype selective, antagonist 7,8-(methylenedioxi)-14
      alpha-alloberbane HCl (CH-38083) (50-100 micrograms/kg, IV) significantly (p <
      0.05) inhibited the pressor effects of epinephrine and norepinephrine given
      intravenously and phase II of the DMPP-induced pressor reaction. Idazoxan exerted
      similar effects, but at higher doses (400-600 micrograms/kg, IV). WB-4101 (50-100
      micrograms/kg, IV) and BRL-44408 (2-3 mg/kg, IV), two selective alpha 2A
      adrenoceptor antagonists, had the same activity as CH-38083, except did not
      inhibit the pressor effect of intravenously administered norepinephrine. The
      alpha 2B-adrenoceptor selective antagonist, ARC-239 (150 micrograms/kg, IV) did
      not influence phase II of DMPP-induced pressor reaction. Prazosin (200
      micrograms/kg, IV), an antagonist of alpha 1 and alpha 2B-adrenoceptors, reduced
      blood pressure, the pressor response to intravenously administered epinephrine,
      and phase I of the DMPP-induced pressor effect. In addition, it completely
      inhibited the pressor responses to DMPP remaining after administration of CH
      38083. These results suggest that the postsynaptically located alpha 1- and alpha
      2(A and B)-adrenoceptors are involved in pressor response to norepinephrine and
      epinephrine, and are sensitive and accessible to catecholamines released locally
      from the axon terminals, and from the circulation to a different extent. These
      results may have great therapeutical importance in hypertension, for which the
      involvement of both a high level of circulating and locally released
      catecholamines may be indicative of the usefullness of a combination (alpha 1-
      and alpha 2-adrenoceptors- and Ca-channel-blocking agents) therapy.

PMID- 8978935
TI  - Cholinesterase inhibition improves blood flow in the ischemic cerebral cortex.
AB  - The ability of central cholinesterase inhibition to improve cerebral blood flow
      in the ischemic brain was tested in Sprague-Dawley rats with tandem occlusion of
      left middle cerebral and common carotid arteries. Cerebral blood flow was
      measured with lodo- 14C-antipyrine autoradiography in 170 regions of cerebral
      cortex. The regional distribution of blood flow was characterized in normal
      animals by cerebral blood flow maxima in the temporal regions. After 2 h
      ischemia, minimum cerebral blood flow values were found in the lateral frontal
      and parietal areas on the left hemisphere, and a new maximum was found in the
      right hemisphere in an area approximately symmetrical to the ischemic focus.
      Heptyl-physostigmine (eptastigmine), a carbamate cholinesterase inhibitor with
      prolonged time of action improved cerebral blood flow in most regions, with the
      exception of the ischemic core. The drug also enhanced the ischemia-induced
      rostral shift of cerebral blood flow maxima in the right hemisphere. The effects
      of eptastigmine were more marked 24 h after ischemia. Discriminant analysis
      showed that data from only 22 regions was sufficient to achieve 100% accuracy in
      classifying all cases into the various experimental conditions. The
      redistribution of cerebral blood flow to the sensorimotor area of the right
      hemisphere of animals with cerebral ischemia, a phenomenon possibly related to
      recovery of function, was also enhanced by eptastigmine.

PMID- 8978937
TI  - Efficacy and effectiveness in the antidepressant treatment of depression: beyond
      metaanalysis.

PMID- 8978936
TI  - Differential effects of the M1-M5 muscarinic acetylcholine receptor subtypes on
      intracellular calcium and on the incorporation of choline into membrane lipids in
      genetically modified Chinese hamster ovary cell lines.
AB  - We compared responses of Chinese hamster ovary (CHO) cell lines stably
      transfected with human genes for the M1-M5 muscarinic receptor subtypes to
      several stimuli. While ATP brought about similar increases in the concentration
      of intracellular Ca2+ ions ([Ca2+]i) in the cell lines expressing all individual
      receptor subtypes, carbachol acted with much higher potency and efficacy on the
      cells expressing the M1, M3, and M5 receptor subtypes than on those expressing
      the M2 and M4 subtypes. The maximum [Ca2+]i responses to ATP corresponded to 41
      75% of the maximum responses to carbachol in the cells expressing the M1, M3, and
      M5 receptor subtypes. The responses to ATP were strongly suppressed (> 75%
      decrease) by a preliminary administration of a maximally active concentration of
      carbachol in these three cell lines, whereas the responses to carbachol were less
      sensitive to the preliminary administration of a maximally active concentration
      of ATP (< 25% decrease). It appears likely that carbachol and ATP release Ca2+
      ions from identical intracellular stores. Tetradecanoylphorbol acetate (TPA)
      strongly inhibited the responses of [Ca2+]i to both carbachol and ATP and
      enhanced the incorporation of [14C] choline into lipids in all five CHO cell
      lines investigated. On the other hand, the incorporation of [14C] choline into
      lipids was diminished by carbachol in the cell line expressing the M3 receptor
      subtype and unchanged in the other cell lines. This effect of carbachol was not
      dependent on the presence of extracellular Ca2+ ions and was not affected by TPA,
      which diminished the response of [Ca2+]i to muscarinic stimulation. It is
      suggested that it was due to muscarinic receptor-mediated activation of
      phospholipase D.

PMID- 8978938
TI  - Antidepressant treatment of depression: a metaanalysis.
AB  - OBJECTIVE: To carry out a metaanalysis of antidepressant studies to calculate the
      effect sizes for antidepressant effect in depressive disorder. METHOD: A
      metaanalysis of all antidepressant studies that included an active comparison
      drug as well as placebo was used to calculate the effect size. Articles were
      selected from a MEDLINE search for the period January 1966 to June 1995. Forty
      nine studies were included in the metaanalysis. RESULTS: The effect sizes for
      antidepressant treatment are moderately larger than for placebo. A larger effect
      size was observed in studies where objective diagnostic criteria for depression
      were used. CONCLUSIONS: We conclude that the superior efficacy of antidepressants
      over placebo can be demonstrated.

PMID- 8978939
TI  - Improving the management of patients with schizophrenia in primary care:
      assessing learning needs as a first step.
AB  - OBJECTIVE: To assess family physician learning needs related to the care of
      patients with schizophrenia. METHODS: Questionnaires were mailed to all family
      physicians and general practitioners practising in southern Alberta. Physicians
      were asked to indicate the number of patients with schizophrenia cared for, their
      interest in improving the care the provided, their preferred learning methods,
      and the content they wished to learn. RESULTS: A total of 539 surveys were
      returned for a return rate of 43.8%. Over half of the physicians (53.5%)
      indicated that they saw 1 to 2 patients with schizophrenia each month. Almost
      half (48.5%) indicated they were somewhat or very interested in increasing the
      care provided. Primary learning needs included increasing their knowledge of
      psychopharmacologic agents and monitoring and adjusting medications. Lectures and
      half-day workshops were the preferred learning methods. CONCLUSION: Our study was
      helpful in identifying the types of education that physicians wanted as well as
      the duration of the programming prior to the development of teaching
      interventions.

PMID- 8978940
TI  - Teaching child and adolescent psychiatry to family medicine trainees: a pilot
      experience.
AB  - OBJECTIVE: To develop learning objectives for teaching child psychiatry to family
      medicine trainees and to evaluate the best method of teaching these objectives.
      METHOD: For this descriptive study, knowledge, attitude, and skill objectives
      were presented to trainees at the start of a 6-month rotation, and an evaluation
      mechanism was developed based on the learning objectives. The method of
      instruction in each of the training locations was described independently by the
      child psychiatry consultant and attending family physician. The trainees'
      evaluations were presented according to training locations. RESULTS: Family
      medicine trainees perceived the teaching-consultation method, with live
      interviews, to be the most helpful and the didactic lecture format to be least
      helpful. CONCLUSION: The importance of teaching family medicine residents to
      recognize mental health problems in children and adolescents, preferably by using
      live interviews, and the implications for postresidency practice are emphasized.

PMID- 8978941
TI  - Acute day hospitalization as an alternative to inpatient treatment.
AB  - OBJECTIVE: This paper describes the administrative process by which the Ottawa
      General Hospital (OGH) closed 6 beds and used the staff and space resources thus
      released to set up an acute day hospital (ADH) for the treatment of 8 acutely ill
      psychiatric patients. Outcome data are presented on the first 160 patients
      admitted to the ADH. METHODS: Demographic and clinical information including
      diagnostic (DSM-III-R; Global Assessment of Functioning [GAF]) and questionnaire
      data (Symptom Checklist-90 Revised [SCL-90R]; Beck Depression Inventory [BDI];
      State-Trait Anxiety Inventory [STAI]; patient satisfaction) were obtained from
      160 ADH patients at admission and discharge. Forty-two of these patients provided
      follow-up data 3 to 6 months postdischarge. The outcome of ADH patients was
      compared with that of a retrospectively obtained random sample (n = 100) of
      inpatients on selected diagnostic and demographic variables. RESULTS: On
      clinician-rated and self-report clinical scales, ADH patients showed significant
      clinical improvement reflected in higher GAF scores and less psychological
      distress, depression, and anxiety at discharge relative to admission. There were
      no significant group differences in outcome indices except for shorter length of
      stay in the ADH group compared with inpatients. The ADH group rated the program
      highly in help received and quality of service. Short-term follow-up showed that
      gains made during treatment were maintained 3 to 6 months later. CONCLUSIONS:
      These results show that a time-limited day hospital program is clinically
      effective for acutely ill psychiatric patients and leads to a more efficient use
      of inpatient resources. We believe that partial hospitalization for the treatment
      of acute psychiatric disorders may have wide application in psychiatric hospital
      practice.

PMID- 8978942
TI  - Psychogeriatric consultation services: effect and effectiveness.
AB  - OBJECTIVES: To determine the nature of referrals to a psychogeriatric
      consultation/outreach service, the types of interventions provided, and the
      effects and effectiveness of the service. METHOD: The study used a prospective
      approach in which 67 consecutive patients referred for psychogeriatric assessment
      were followed up 6 to 8 weeks after the initial assessment and then again 6
      months after initial contact. Patients were rated at the time of referral and at
      follow-up on presence of psychiatric diagnosis, need for institutional care, and
      placement outcome. RESULTS: Of the 67 patients initially seen, 51 (76%)
      experienced memory problems and 46 (69%) had depressed mood. Consistent with this
      finding, 36 (54%) were diagnosed by consultants as having a dementia, and 15
      (22%) received a diagnosis of depression. The most frequent recommendations
      included medication changes in 34 cases (50%) and further assessments in 37 cases
      (55%). Although information at 6-week follow-up was available for only 58% (n =
      38) of the sample, 18 (46%) patients were generally improved. Interestingly, only
      12 (31%) of referring physicians indicated that they had followed the advice of
      the consultants. Cognitive impairment and depressive symptoms were major concerns
      among referring physicians. The most common recommendation made involved
      pharmacotherapy. While compliance of family doctors to recommendations made was
      poor, patients improved over time. Patients requiring inpatient assessment were
      very old, living alone, experiencing behavioural problems, and not depressed.
      CONCLUSIONS: Psychogeriatric consultations appear most useful in cases where
      patients are more severely affected and/or are suffering from a greater range of
      symptoms.

PMID- 8978943
TI  - Familial dementia of frontal lobe type.
AB  - OBJECTIVE: To describe an unusual case of familial frontal lobe dementia (FLD)
      with probable spongiform encephalopathy (SE). METHOD: The patient's clinical
      presentation, neuropsychological test results, family history, and results on
      magnetic resonance imaging (MRI) and positron emission tomography (PET) scans,
      among other routine investigations, are described. His leucocyte
      deoxyriboneucleic acid (DNA) was isolated, and his Prp (prion protein) gene was
      amplified with the polymerase chain reaction and sequenced using the Sanger
      method. RESULTS: Clinically, the patient had a presenile frontal lobe dementia.
      Four of the 8 members of the generation preceding the patient had presenile
      dementia. Autopsies performed on 2 of these cases revealed SE, and a pathological
      diagnosis of Creutzfeldt-Jakob disease (CJD) was made. One other member of that
      generation died of a limbic encephalitis, although the neuropathological findings
      were atypical. Sequencing of the patient's Prp gene did not reveal the
      abnormalities expected in a familial case of CJD. The results of other
      investigations were compatible with FLD but were not specific to a particular
      diagnosis. CONCLUSIONS: This case is a novel type of SE. The patient presented
      clinically with FLD, but based on the family history and neuropathology, a
      diagnosis of prion dementia seems likely. There were no mutations found in the
      Prp gene, so it is possible that there are SEs caused by genes or other
      pathological processes unrelated to the Prp gene.

PMID- 8978944
TI  - Self-induced water intoxication treated with risperidone.
AB  - OBJECTIVE: To determine whether or not risperidone is efficacious in treating
      self-induced water intoxication in patients with chronic schizophrenia. METHOD:
      We carried out a prospective 11-month open-label study using risperidone to treat
      8 men with chronic schizophrenia and self-induced water intoxication. RESULTS:
      The 8 men were not able to reduce their fluid consumption compared with their
      baseline intake. Risperidone, however, significantly decreased the Brief
      Psychiatric Rating Scale (BPRS) scores of this very chronic group. CONCLUSIONS:
      Although risperidone decreased schizophrenic symptoms, it did not have
      significant efficacy in treating self-induced water intoxication. This study may
      have implications for the treatment of addictive behaviour.

PMID- 8978945
TI  - Depressive symptoms attributable to medication exposure in a medical inpatient
      population.
AB  - OBJECTIVE: Exposure to certain drugs-angiotensin-converting enzyme inhibitors,
      beta-blockers, calcium channel blockers, corticosteroids. H2 blockers, and
      sedative hypnotics-may be associated with an increased risk of depression. These
      drugs are commonly used in inpatient medical therapeutics. Since population
      attributable risk (PAR) is generally related both to strength of association and
      to the frequency of exposure to a risk factor, the PAR of depressive symptoms
      associated with these drug exposures is potentially high. The objective of this
      study was to estimate the depressive symptoms population attributable risk
      percent (PAR%) in a medical inpatient population. METHODS: A prospective cohort
      design was used in this study. Nondepressed, nondrug-exposed subjects (N = 178)
      were selected from a series of 369 newly admitted medical inpatients at the
      Calgary General Hospital. Eighty-six of these 178 subjects were prescribed one of
      the drugs in question, forming an exposed cohort. The remaining subjects formed a
      nonexposed cohort. Depressive symptoms and associated psychosocial variables were
      measured in both subgroups during the hospital stay. RESULTS: Seventeen of the 86
      exposed subjects and 5 of the 92 nonexposed subjects developed incident
      depressive symptoms during their stay in hospital. The PAR% associated with drug
      exposure (56.0%) exceeded that associated with poverty (17.9%) or unemployment
      (21.7%). CONCLUSIONS: Drug exposures may have a sizeable impact on the incidence
      of depressive symptoms in medical inpatient populations.

PMID- 8978946
TI  - Re: Adult recovered memories of childhood sexual abuse.

PMID- 8978947
TI  - Re: Competency.

PMID- 8978948
TI  - Heart rate, breathing, and subjective responses of a limited-symptom panic
      patient to 35% carbon dioxide challenge.

PMID- 8978949
TI  - Fluvoxamine-clozapine dose-dependent interaction.

PMID- 8978950
TI  - Medical management of lower limb osteoarthritis: practice guidelines from the UK
      and USA compared.

PMID- 8978951
TI  - Pooled human immunoglobulins contain anti-idiotypes with reactivity against the
      SLE-associated 4B4 cross-reactive idiotype.
AB  - OBJECTIVE: To identify anti-idiotype antibody activity against a regulatory anti
      Sm idiotype (4B4) in pooled human IgG (IVIG). METHODS: ELISA were used to
      determine anti-idiotype antibody activity in IVIG. RESULTS: Anti-idiotype
      antibody activity to 4B4 was detected in IVIG. The anti-idiotypic activity in
      IVIG could be inhibited by antigen, Sm, and rabbit anti-idiotypic antiserum. The
      idiotypic binding activity was predominately directed against the 4B4 VH region.
      CONCLUSION: IVIG contains antibodies against a lupus-associated crossreactive
      idiotype. These antibodies represent Ab2 beta type antibodies. The anti-idiotypic
      activity in IVIG may be relevant to the efficacious use of IVIG in treating
      rheumatic diseases.

PMID- 8978952
TI  - Lipoproteins, anticardiolipin antibodies and thrombotic events in rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate lipoprotein levels in rheumatoid arthritis (RA)
      patients with and without anticardiolipin antibody (aCL) positivity and to
      evaluate whether an abnormal lipid profile might be associated with an altered
      risk of vascular disorders. METHODS: 137 female patients were evaluated for their
      aCL levels (isotypes IgG and IgM); concentrations of plasma lipids, lipoproteins,
      and apolipoproteins; and for the occurrence of thrombotic events. The patients
      were grouped according to their aCL positivity. RESULTS: Higher rates of venous
      and/or arterial thrombosis were diagnosed in all the RA patients compared to the
      controls (p = 0.01). Lower levels of the high density lipoprotein cholesterol,
      apolipoprotein AI, were found in these patients (p = 0.001). Higher levels of
      lipoprotein (a) were observed in RA patients when compared to controls in both
      aCL positive and negative RA patients (P = 0.001 and p = 0.01, respectively).
      CONCLUSION: The presence of aCL and an altered lipid profile may represent an
      important risk factor for thrombotic events in patients affected by RA.

PMID- 8978953
TI  - Peripheral nervous system involvement in systemic sclerosis: the median nerve as
      target structure.
AB  - OBJECTIVES: To investigate the frequency and the main electrophysiological
      characteristics of the canalicolar passage nerve involvement in patients with
      systemic sclerosis (SSc). METHODS: Thirty-two SSc patients were enrolled in the
      study, classified according to the type (diffuse or limited) and the duration (>
      / < 5 years) of the disease. Sensory-motor nerve conduction studies (NCS) of the
      upper and lower limbs, in particular at the critical canalicolar points, were
      conducted by recording the Compound Muscular Action Potential (CMAP) and the
      Sensory Action Potential (sNAP). The following parameters were evaluated: Motor
      Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity; distal
      and proximal latency of the CMAP and the onset and peak latency of the sNAP; peak
      peak amplitude and negative-peak area of the CMAP and sNAP; and the Terminal
      Latency Index (TLI) (Terminal Distance/MCNV x Distal latency). RESULTS: Four
      (12.5%) patients had a distal neuropathy of the upper limbs (one with monolateral
      and two with bilateral involvement of the median nerve and one bilateral
      involvement of the ulnar nerve). Fourteen (43.7%) patients showed a decrement of
      the median nerve TLI and seven (21.8%) of either the median or the ulnar nerve
      (Table I). Motor and sensitive conduction velocity and latency studies did not
      show a statistical difference between SSc patients and controls. The amplitude
      and area of the CMAP (distal and proximal), sNAP and of the median nerve TLI were
      significantly decreased in patients with respect to controls. CONCLUSION: Distal
      mononeuropathy of the median nerve was the most frequent result in our patients.
      The involvement of the peripheral nervous system seems to be strictly
      topographical, following the modifications of the tissues and vascular tone
      (Raynaud's phenomenon) at the upper acral level. The neurophysiological
      alterations detected in our study at the wrist level may not be linked merely to
      a compressive event but also to microvascular involvement. Nerve involvement
      closely connected with the pathogenesis and distribution of SSc should be
      considered when peripheral nervous system involvement is the initial symptom of
      the disease.

PMID- 8978954
TI  - Antibody epitopes probed by immunoselected phage-display library peptides in
      members of a family with various rheumatic manifestations.
AB  - OBJECTIVE: The random peptide combinatorial phage library approach overcomes the
      problem of lack of structural information about the aetiological agent or the
      antigen responsible for a given disease. Here, we used such a strategy to gain
      insight into the aetiology of rheumatoid arthritis (RA). METHODS: We analyzed the
      reactivity of serum antibodies from a family with various rheumatic
      manifestations against RA-immunoselected nanopeptides displayed on phage
      particles. RESULTS AND CONCLUSION: We found that within the same family, there
      was a difference in antibody reactivity against the peptides tested. The IgG
      isotype of the peptide reactive antibodies indicated that the observed
      reactivities were not related to the presence of polyreactive IgM antibodies.
      Furthermore, it is unlikely that the observed reactivity was due to rheumatoid
      factors (RF), since two patients who were positive for the immunoselected Pep3
      peptide (LSSREPQAR) were RF negative. We also found that the serum of one patient
      with polyarthralgias also reacted with the same peptide bound by the RA serum,
      which may suggest the implication of a common aetiological agent in the
      apparition of this antibody reactivity. Finally, we noted that one patient with
      Sjogren's syndrome had antibodies to the RA peptide, which may indicate a
      potential relationship between these two autoimmune diseases.

PMID- 8978955
TI  - Plasma renin activity as a marker of renovascular injury in patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: To assess whether plasma renin activity (PRA) in patients with
      rheumatoid arthritis (RA) and evidence of renal involvement (microhematuria) can
      serve as potential marker of renovascular injury. METHODS: PRA was measured at
      rest and following exercise. All nonsteroidal antiinflammatory drugs or other
      medications that might affect renin release were stopped at least ten days prior
      to PRA measurements. PRA was correlated with the number of dysmorphic
      erythrocytes present in the urine sediment as indicators of glomerular capillary
      injury (microhematuria). RESULTS: All patients with RA had a higher mean PRA than
      controls. Moreover, all patients with RA in whom microhematuria was present had a
      higher PRA than those without microhematuria. Simple and multiple regression
      analysis revealed a significant correlation between: a) PRA and rheumatoid factor
      levels; b) rheumatoid factor levels and the number of erythrocytes in the urine
      sediment; and c) PRA levels and the number of erythrocytes in the urine sediment.
      CONCLUSIONS: The observations indicate that increased PRA may occur in
      normotensive patients with RA and no clinical or biochemical evidence of renal
      involvement. This may reflect activation of the renin-angiotensin system. The
      positive correlation between enhanced PRA, rheumatoid factor levels and
      microhematuria in RA patients may indicate inflammatory injury of the glomerular
      microvasculature involving the juxtaglomerular apparatus.

PMID- 8978956
TI  - Effects of orally administered bisphosphonates on bone loss in a disuse
      osteopenia model involving the rat.
AB  - OBJECTIVE: This study was carried out to evaluate the effectiveness of two newly
      synthesized bisphosphonates (BPs) [Alendronate (4-amino-1-hydroxybutylidene-1, 1
      bisphosphonic acid (AHBuBP)) and Neridronate (6-amino-1-hydroxyhexylidene-1,1
      bisphosphonic acid (AHHexBP)], administered orally, in reducing experimentally
      induced bone loss. METHODS: Unilateral sciatic nerve section was performed on the
      Sprague-Dawley rat to induce osteopenia in one of the hind limbs.
      Histomorphometric measurements of the tibial trabecular bone and femur ash
      content determinations were effected to assess the degree of osteopenia. For
      comparison Chlodronate (dichloromethylene-1-bisphosphonic acid (Cl2MBP) was
      employed as the reference drug. CONCLUSIONS: The results of this investigation
      show that both BPs were significantly active in reducing the osteopenic process
      in the involved limb and were more active than Chlodronate.

PMID- 8978957
TI  - D-penicillamine in early rheumatoid arthritis: experience from a 2-year double
      blind placebo controlled study.
AB  - OBJECTIVE: To evaluate the usefulness of early treatment with D-Penicillamine
      (DPA) in rheumatoid arthritis. METHODS: The patients were recruited from a
      Swedish early RA cohort comprising 180 patients. All patients experiencing active
      and/or erosive disease 2 years from onset were asked to participate in a 2-year
      placebo-controlled DPA trial. Previous treatment with slow-acting anti-rheumatic
      drugs (SAARDs) or oral corticosteroids was not allowed. The main outcome variable
      was radiographic progression in the hands and feet evaluated according to Larsen.
      Clinical assessment including the Ritchie index, active joint count, and the HAQ
      disability index was performed every 6th month. Patients were included in the
      analyses of efficacy until the endpoint of therapy. RESULTS: 111/180 patients
      were eligible for treatment, and 74 agreed to participate in the trial. 21/33
      patients on DPA and 22/41 on placebo completed the study. More patients taking
      placebo stopped due to lack of response (p < 0.01). 27% of the patients on DPA
      were withdrawn due to side effects. Radiographic deterioration increased but most
      clinical variables improved in both trial arms. A large inter-individual
      variation was observed. The only significant difference in trend over 2 years
      between DPA and placebo was found for joint tenderness. However, the median
      trends for most clinical variables showed a more positive effect for DPA. The 37
      patients who refused to participate in the trial in general fared somewhat worse
      than patients taking DPA and somewhat better than patients taking placebo. The
      remission rate was about the same in all 3 groups (12-13.5%). CONCLUSIONS: About
      two-thirds of all early definite RA patients were eligible for treatment using
      current criteria. Psychological readiness for early therapy was fairly modest
      with a high refusal rate. The difference in efficacy between DPA and placebo was
      small, but was in favour of DPA for most clinical variables. However, only joint
      tenderness showed a significantly better trend. No significant slowing of
      radiographic progression by DPA was found.

PMID- 8978958
TI  - Pathologic study of an experimental canine arthritis induced with Complete
      Freund's Adjuvant.
AB  - OBJECTIVE: To describe the physiopathological features of an experimental
      monoarthritis in a canine model. METHODS: Pathological changes of the
      femorotibial joints, periarticular tissues and lymphoid organs were investigated
      by histology, immunohistochemistry, flow cytometry and cytokine bioassays after
      intra-articular administration of Complete Freund's Adjuvant in dogs. RESULTS: An
      edematous acute synovitis with considerable diapedesis of the neutrophilic
      granulocytes was observed during a primary response. This was followed by a
      clinical remission, although a multifocal subacute synovitis was noted with
      inflammatory infiltrates of mononuclear cells (macrophages > CD8 > CD4). Blood
      CD14 expression was upregulated and the percentage of CD8+ cells was
      significantly decreased. Two to four weeks post-induction, a decrease in
      functional impotency (secondary response) and a pyogranulomatous periarthritis
      with intramuscular extensions were noted. Focal cartilage erosion was due to
      adherent granulation tissue (CD4 > CD8 > macrophages). CONCLUSION: In this canine
      model, experimentally induced arthritis was mainly the result of a cell-mediated
      immune reaction towards a non-identified antigen.

PMID- 8978959
TI  - Tumor necrosis factor-alpha (TNF-alpha) in loosening of total hip replacement
      (THR).
AB  - OBJECTIVE: The initially well-fixed implants of total hip replacement (THR) are
      in the long-term subject to aseptic loosening. Many cytokines can contribute to
      osteolysis due to osteoclast recruitment and/or activation. However, in this
      respect tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role, because it
      upregulates interleukin-1 and 6 and granulocyte-macrophage colony stimulating
      factor. The aim of this study was to assess the eventual presence, cellular
      localization and extent of expression of TNF-alpha in the synovial-like membrane
      at the implant or at the cement to bone interface compared to control synovial
      membrane. METHODS: Twenty samples from the synovial-like membrane of the
      periprosthetic tissues were compared to control samples. TNF-alpha containing
      cells were visualized using an avidin-biotin-peroxidase complex (ABC) method and
      analyzed by light microscopy, double labelling and image analysis. RESULTS: TNF
      alpha was found in the periprosthetic tissues in fibroblasts and vascular
      endothelial cells, but mainly in the macrophages was it found to coincide with
      areas containing implant-derived debris. TNF-alpha containing cells were more
      numerous in the synovial-like membrane in the interface tissue from the proximal
      stem area (2816 +/- 318 cells) than in the control synovial membrane (565 +/- 93
      cells, p < 0.01). Interestingly, similarly high TNF-alpha expression (3452 +/-
      582 cells) was also seen in the synovial-like membrane of the pseudocapsule.
      CONCLUSION: These findings suggest that the foreign body-type host reaction
      caused by THR is characterized by the high expression of TNF-alpha. Because such
      expression occurred in the interface tissue between the implant and surrounding
      bone, TNF-alpha, due to its pivotal direct and indirect role in the activation
      and recruitment of osteoclasts, may contribute to periprosthetic osteolysis and
      to the loosening of THR.

PMID- 8978960
TI  - Laser Doppler perfusion imaging of proximal interphalangeal joints in patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: A non-invasive imaging technique (laser Doppler perfusion imaging-LDI)
      based on measurement of backscattered Doppler-broadened near infra-red laser
      radiation was used to provide two-dimensional images of perfusion over the
      proximal interphalangeal (PIP) joints of a group of normal subjects compared to a
      group of patients with rheumatoid arthritis (RA). RESULTS: Some PIP joints of the
      RA group showed areas of increased perfusion whereas normal subjects showed much
      less variation in perfusion between joints. These hyperaemic areas arose from the
      underlying joint, as scans taken with a less penetrating red laser did not show
      such areas. CONCLUSION: Apart from its obvious dermatological uses, LDI could be
      employed to image hyperaemia associated with a variety of inflammatory conditions
      affecting subcutaneous structures.

PMID- 8978961
TI  - Interleukin 6: a possible marker of disease activity in adult onset Still's
      disease.
AB  - OBJECTIVE: Adult onset Still's disease (AOSD) is an inflammatory disorder with
      elevated serum acute phase proteins. Interleukin-6 is a major contributor to the
      acute phase response. We therefore examined the serum levels of CRP, SAA and
      interleukin-6 in active and inactive AOSD. RESULTS: Active patients had
      significantly elevated CRP, SAA, and interleukin-6 values. After steroid
      treatment a marked reduction was observed in all three parameters. There was a
      close kinetics on the fluctuations of CRP and SAA, but not on IL-6. CONCLUSION:
      Acute phase proteins and IL-6 are useful markers of disease activity in AOSD.

PMID- 8978962
TI  - High dose intravenous immunoglobulin (IVIg) in severe refractory rheumatoid
      arthritis: no evidence for efficacy.
AB  - OBJECTIVE: A number of reports have recently suggested that high doses of
      intravenous immunoglobulins may exert beneficial effects in rheumatoid arthritis.
      One proposed mechanism for this effect is suppression of the generation of pro
      inflammatory cytokines, particularly tumor necrosis factor alpha (TNF alpha). We
      have undertaken a prospective open study of IVIg in patients with severe
      refractory RA who have failed at least four second line drugs, including
      methotrexate, and who were receiving NSAIDs and prednisone only. METHODS: Four
      patients, 3 males and 1 female, with an average age of 58.25 years (range 41-69
      years) and a mean disease duration of 13 years (range 9-14 years), were given
      IVIg at a dose of 1 g per day for 2 days once a month for 3 months. All patients
      had active disease at baseline as indicated by an average tender joint count of
      15 and an average swollen joint count of 15.25. Clinical assessments were
      performed according to the WHO/ILAR recommendations at baseline and at monthly
      intervals up to 4 months after the initiation of IVIg therapy. Patients were
      classified as responders or non-responders according to the Paulus criteria.
      Laboratory assessment included a CBC, ESR, and whole blood cytokine ELISA for TNF
      alpha, TNF R1, and TNF R2 at baseline, 1 day, 7 days and 3 months after the
      initiation of therapy. RESULTS: None of the patients met the Paulus criteria for
      either improvement or worsening. Furthermore, increased TNF alpha production in
      lipopolysaccharide (LPS) stimulated whole blood assays was consistently noted in
      3 out of the 4 patients during the course of therapy which, together with the
      lack of clinical efficacy, prompted us to curtail further evaluation of this
      therapy. CONCLUSION: We were unable to discern any beneficial effects of IVIg
      therapy, and suggestions that it may enhance TNF alpha generation as well as its
      substantial cost mandate caution in the future use of this agent in RA.

PMID- 8978963
TI  - LMP polymorphisms do not influence disease expression in psoriatic arthritis.
AB  - OBJECTIVES: To investigate the potential role of the HLA-linked LMP2 (low
      molecular weight protein) and LMP7 gene polymorphisms in conjunction with HLA
      class I and class II genes on the disease pattern in individuals with psoriatic
      arthritis (PsA). METHODS: Sixty-three patients with PsA and 99 unrelated controls
      were typed for HLA-class I and II antigens. LMP2 and LMP7 polymorphisms were
      determined by PCR and subsequent single stranded conformation polymorphism (SSCP)
      analysis or restriction enzyme digestion. RESULTS: PsA was associated with B27 (p
      < 0.0004), B57 (p < 0.002) and Cw2 (p < 0.008). Spondylarthritis was strongly
      associated with HLA-B27 (p < 0.000001), Cw2 (p < 0.0003) and DR4 (p < 0.008). For
      the polyarthritic pattern the only association was with B57 (p < 0.007). There
      was no association between the LMP2 or LMP7 genotypes and any particular disease
      pattern. CONCLUSIONS: These findings do not support an involvement of the HLA
      linked LMP2 and LMP7 gene polymorphisms in disease expression in psoriatic
      arthritis in addition to the known HLA class I and II associations.

PMID- 8978964
TI  - Etiological factors and underlying conditions in patients with leucocytoclastic
      vasculitis.
AB  - This study concerns a retrospective analysis of 63 consecutive patients
      presenting with leukocytoclastic vasculitis at the Departments of Dermatology or
      Rheumatology of the University Hospital Ghent (Belgium) (period 1988-1993). The
      diagnosis of leukocytoclastic vasculitis was confirmed by histopathology in all
      cases. All patients were screened for underlying causes, including drugs,
      infection, systemic autoimmune disease or neoplasia. In 34 patients, an
      etiological factor was identified: drugs (5 patients), infection (6 patients),
      drugs or infection (4 patients), systemic autoimmune disease (10 patients),
      Henoch Shonlein (6 patients), neoplasia (2 patients) and cryoglobulinemia (1
      patient). In the group of patients with leukocytoclastic vasculitis in the
      context of systemic autoimmune disease, 4 patients suffered from systemic lupus
      erythematosus, 2 from Wegener's disease, 2 from Behcet's disease, 1 from
      polyarteritis nodosa and 1 from rheumatoid arthritis. In the remaining 29
      patients, no cause for the vasculitis could be identified.

PMID- 8978966
TI  - Vasculitis in systemic lupus erythematosus following intravenous immunoglobulin
      therapy.
AB  - We describe a 6-year-old female patient with systemic lupus erythematosus (SLE)
      manifested mainly as steroid-dependent thrombocytopenia who developed a
      vasculitic appearing rash on her palms and soles following treatment with
      intravenous immunoglobulin (IVIg) (1 gm/kg/infusion x 2, 1 day apart). Vascular
      occlusion resulting in ischemic gangrene of the fore and midfeet eventually
      developed, necessitating bilateral amputation. This and other side effects
      described in SLE indicate that exacerbation of SLE, with the possibility of
      vasculitis, may occur following IVIg therapy.

PMID- 8978965
TI  - Y box-binding trans-regulatory nuclear proteins and susceptibility to rheumatoid
      arthritis.
AB  - OBJECTIVE: Inappropriately high levels of expression of HLA-DR molecules or their
      expression on inappropriate cells, e.g. synovial tissue and T cells, may result
      in an aberrant tissue-destructive immune response and thus cause susceptibility
      to rheumatoid arthritis (RA). METHODS: Patients and controls were typed for HLA
      DR antigens by oligonucleotide typing of PCR-amplified DNA. Trans-regulatory
      nuclear proteins that bind to the Y box in DRB promotors were examined by the gel
      mobility shift assay. RESULTS: We found that the trans-regulatory nuclear protein
      (NF-Y), which binds to the Y box in DRB promoters and which plays a dominant role
      on the level of the expression and inducibility of DR genes, was absent in 50% of
      RA patients but not in healthy individuals (0%). Furthermore, we observed that
      all patients (100%) either lacked the NF-Y protein and/or carried the disease
      susceptibility DRB1 gene, which gives the highest relative risk value (RR = 46.6;
      p < 1.6 x 10(-6)) reported so far for susceptibility to RA. CONCLUSION: The
      absence of the trans-regulatory nuclear protein that binds to the Y box with an
      inverted CCAAT motif in DRB promotors and the presence of the DRB1 gene with the
      amino acid motif QKRAA and QRRAA cause susceptibility to RA.

PMID- 8978967
TI  - Transient regional osteoporosis with antiphospholipid antibodies: a report of two
      cases.
AB  - We describe two patients with clinical, radiological and laboratory findings
      consistent with transient regional osteoporosis. In both cases antinuclear and
      antiphospholipid antibodies were found with no evidence of any other autoimmune
      disease. Both patients were smokers. We suggest transient ischemia caused by
      antiphospholipid antibodies as a possible etiological factor in this rare and
      poorly understood syndrome, and hypothesize that anticoagulants and abstinence
      from smoking may play a role in the prevention of recurrence in these patients.

PMID- 8978968
TI  - The potential of bronchoalveolar lavage in the prognosis and treatment of
      connective-vascular diseases.
AB  - Interstitial lung disease (ILD) has a poor prognosis in a significant number of
      patients with connective vascular disease (CVD). By bronchoalveolar lavage fluid
      (BALF) analysis, ILD may be demonstrated in nearly half of patients with CVD
      prior to any alteration in lung function or chest radiograph. High neutrophil and
      eosinophil counts are usually associated with a high risk of functional
      deterioration, whereas the presence of increased lymphocytes correlates with a
      better outcome. Furthermore, initiation of therapy (steroids and/or cytotoxic
      agents) early in the course of disease is predictive of a better response. Cell
      differentials in bronchoalveolar lavage (BAL), together with measurements of cell
      by-products and techniques such as high resolution computed tomography, may
      contribute in the near future to help characterize those patients with the
      highest risks of evolution to pulmonary fibrosis, and to determine the most
      favorable time in the course of the disease for the initiation of therapy.

PMID- 8978969
TI  - Juvenile onset of primary Sjogren's syndrome: report of 10 cases.
AB  - OBJECTIVE: Ten new cases with primary Sjogren's syndrome (pSS) whose disease
      began before age 16 are described. Special attention is paid both to the follow
      up and treatment of this condition. METHODS: Cases with juvenile pSS were
      retrospectively identified from our series of 180 pSS patients. Ocular, salivary,
      and extraglandular manifestations as well as a full laboratory evaluation
      including HLA-DR typing were retrieved. RESULTS: A disease prevalence of 5.5% (10
      cases, 8 female and 2 male) was found in our series. The mean age at onset was
      11.0 years, but the disease started at the age of 4 in 2 patients. At onset,
      parotid swelling was found in 6 cases and extraglandular manifestations in 3.
      Throughout the follow-up period (mean 48.6 months from the time of diagnosis),
      the clinical picture was similar to that of pSS in adults, but oral involvement
      was generally milder. Extraglandular manifestations were always present but never
      severe. Pertinent laboratory abnormalities (e.g. rheumatoid factor, polyclonal
      hypergammaglobulinemia, leukopenia, increased ESR, ANA and anti-SSA/SSB
      antibodies) were found in all patients. Specifically, ANA and anti-SSA were
      always positive. Moreover, in our cases histocompatibility antigens HLA-DR3 and
      DR 52 were closely associated with the disease. Clinical outcome was difficult to
      predict; however, no serious complications have been observed so far. We obtained
      good results with low-dose steroids and/or hydroxychloroquine, especially with
      regard to the extraglandular manifestations and laboratory abnormalities.
      CONCLUSION: We confirm that juvenile pSS is not a rare condition. It closely
      resembles pSS in adults except for the extremely high prevalence of recurrent
      parotitis and immunological findings.

PMID- 8978970
TI  - Elevated in vivo expression of the costimulatory molecule B7-BB1 (CD80) on
      antigen presenting cells from a patient with SLE.
AB  - The CD28/CTLA4-B7-family plays an important role in T-cell costimulation and is
      crucial for IL-2 production and tolerance induction. The costimulatory molecule
      B7-BB1 (CD80) is expressed on activated antigen presenting cells, but its
      expression on peripheral blood mononuclear cells is very low. Here we report a
      patient with untreated SLE whose peripheral blood antigen presenting cells
      expressed increased amounts of B7-BB1.

PMID- 8978971
TI  - Does coexistence of ochronosis and ankylosing spondylitis really exist?

PMID- 8978972
TI  - Cerebral arteriopathy in scleroderma.

PMID- 8978973
TI  - Pericardial tamponade and systemic sclerosis.

PMID- 8978974
TI  - Cardiomyopathy following intravenous cyclophosphamide therapy in a patient with
      Wegener's granulomatosis.

PMID- 8978975
TI  - Asthma patient education: a primer for the primary care physician.

PMID- 8978976
TI  - Recent advances in the management of opportunistic fungal infections.

PMID- 8978977
TI  - Human babesiosis.

PMID- 8978979
TI  - Cartilage as a target organ in arthritis: new approaches.

PMID- 8978978
TI  - Prevention, diagnosis, and treatment of pediatric HIV infection.

PMID- 8978980
TI  - Current approaches to coronary intervention.

PMID- 8978981
TI  - Disseminated intravascular coagulation: an update.

PMID- 8978982
TI  - Tuberculosis: a primary care perspective.

PMID- 8978983
TI  - Signal processing in the vomeronasal system: modulation of sexual behavior in the
      female rat.
AB  - Chemosensory cues detected by the vomeronasal (VN) organ modulate a variety of
      social interactions in many species. In particular, activation of the VN system
      by pheromones regulates sexual behavior in the rodent. Although the exact nature
      of stimulus access to the organ is not clearly defined, the neuroanatomical
      pathway connecting the VN organ to hypothalamic centers controlling reproductive
      function is well established and relatively straightforward. Electrophysiological
      techniques have provided insight into the signal transduction process throughout
      the VN system. Combining behavioral studies with immunocytochemical detection of
      immediate early genes and neuropeptides reveals that gonadotropin hormone
      releasing hormone (GnRH)-containing neurons are specifically activated by
      stimulation of the VN organ. Furthermore, some of the activated GnRH neurons
      project to the ventromedial hypothalamus where they are hypothesized to induce
      sexual responsiveness. Early anecdotal evidence of an influence of the VN organ
      on human reproductive events has been substantiated by more recent anatomical,
      behavioral, and electrophysiological studies. Thus, further deciphering of the
      signal transduction process within the VN system of the rodent may yield unique
      insights into behaviors associated with human reproduction.

PMID- 8978984
TI  - Neurobiology of nitric oxide.
AB  - Nitric oxide is a ubiquitous and unique biological messenger molecule. It
      mediates blood vessel relaxation by endothelium, immune function of macrophages,
      and neurotransmission of central and peripheral nervous systems. Endothelial and
      neuronal nitric oxide synthases are constitutively expressed and activated by
      calcium entry into cells, whereas the macrophage nitric oxide synthase is
      inducible with new RNA and protein synthesis upon immune stimulation. Nitric
      oxide may play a role in the neurotransmitter release, neural development,
      synaptic plasticity, and regulation of gene expression. Excessive production of
      nitric oxide is neurotoxic and is implicated in a variety of neurological
      disorders.

PMID- 8978985
TI  - The frontal cortex-basal ganglia system in primates.
AB  - The primate basal ganglia receives information from most of the cerebrum,
      including the frontal cortex, but projects (via the dorsal thalamus) primarily to
      the frontal lobe, perhaps in its entirety. As such, the frontal cortex and basal
      ganglia constitute an integrated, distributed neuronal architecture. We review
      evidence that the frontal lobe and basal ganglia specialize in different, but
      related, aspects of response learning. Frontal cortex acts when new rules need to
      be learned and older ones rejected, whereas the basal ganglia potentiate
      previously learned rules based on environmental context and reinforcement
      history. Such potentiation increases the probability that the central nervous
      system will select a particular rule to guide behavior. We outline a possible
      mechanism for the basal ganglia's proposed role in rule potentiation, one that
      involves both the direct and indirect striatal output pathways and their
      dopaminergic input. It has previously been proposed that direct-pathway neurons
      recognize a pattern of corticostriatal inputs, which promotes activity in
      recurrent, positive-feedback modules (or loops) of which they are an integral
      part. We propose that this recurrent activity potentiates a rule associated with
      those modules. If so, then the dopaminergic system is well situated and organized
      to modulate rule potentiation in both the short and long term. Dopaminergic
      neurons of the midbrain increase activity during learning and other periods of
      relatively unpredictable reinforcement. Dopamine enhances gene expression and
      other forms of activity in striatal neurons of the direct pathway, while
      suppressing neurons of the indirect pathway. In the short term, then, dopamine
      may augment the activity of modules triggered by a recognized context, whereas in
      the long term it may promote context-dependent activation of the same modules.
      Together, these modulatory influences could support both rule potentiation and
      learning the context for potentiating that rule.

PMID- 8978986
TI  - Nootropics: preclinical results in the light of clinical effects; comparison with
      tacrine.
AB  - This review is meant to serve several purposes. First, it surveys the preclinical
      and clinical profiles of piracetam-like nootropics. Second, the conditions under
      which the nootropics are active in preclinical studies are identified and
      analyzed with a view of finding a common denominator that could explain the
      observed effects. Third, the clinical profile is examined, on the one hand to
      assess whether these drugs are in fact active in humans, and on the other to
      determine how the clinical effects of the nootropics compare with those of
      tacrine. Lastly, the clinical data are then further scrutinized to assess whether
      they fulfill the expectations based on the preclinical findings.

PMID- 8978987
TI  - Neuronal circuit regulation of the hypothalamo-pituitary-adrenocortical stress
      axis.
AB  - The hypothalamo-pituitary-adrenocortical (HPA) axis is the primary modulator of
      the adrenal glucocorticoid stress response. Activation of this axis occurs by way
      of a discrete set of neurons in the hypothalamic paraventricular nucleus (PVN).
      The PVN neuron appears to be affected by multiple sources, including (1)
      brainstem aminergic/peptidergic afferents; (2) blood-borne information; (3)
      indirect input from limbic system-associated regions, including the prefrontal
      cortex, hippocampus, and amygdala; and (4) local-circuit interactions with the
      preoptic-hypothalamic continuum. Analysis of the literature suggests that
      different classes of stressor employ different stress circuits. Severe
      physiologic ("systemic") stress appears to trigger brainstem/circumventricular
      organ systems that project directly to the paraventricular nucleus. In contrast,
      stressors requiring interpretation with respect to previous experience
      ("processive" stressors) reach the PVN by way of multisynaptic limbic pathways.
      Limbic regions mediating processive stress responses appear to have bisynaptic
      connections with the PVN, forming intervening connections with
      preoptic/hypothalamic GABAergic neurons. Stressors of the latter category may
      thus require interaction with homeostatic information prior to promoting an HPA
      response. The HPA stress response thus appears to be a product of both the
      physiologic importance of the stimulus and the specific pathways a given stimulus
      excites.

PMID- 8978988
TI  - The role of mesoprefrontal dopamine neurons in stress.
AB  - While several catecholaminergic systems are activated by stressful stimuli, the
      mesoprefrontal dopamine (DA) system appears to be particularly vulnerable to
      stress. Low intensity stressors that do not produce detectable effects in most
      ascending catecholaminergic systems activate mesoprefrontal DA neurons.
      Mesoprefrontal DA neurons are unique in that they lack or have decreased
      densities of specific autoreceptors affecting autoregulatory capabilities, which
      could contribute to the fact that mesoprefrontal DA neurons exhibit increased
      rates of burst firing and DA turnover relative to other midbrain dopaminergic
      projections. In addition, mesoprefrontal DA neurons are uniquely modulated by a
      number of chemically distinct afferent influences including gamma-aminobutyric
      acid (GABA), serotonin, excitatory amino acid, substance P, opiate, and
      noradrenergic systems. Any or all of these factors could contribute to the
      selective activation of mesoprefrontal DA neurons following exposure to low
      intensity stressors. The present review summarizes the possible mechanisms by
      which mesoprefrontal DA neurons are preferentially activated by stress. The
      operational significance of this unique neurochemical response to stress is
      discussed in terms of a possible coping versus anxiety function. Also discussed
      are the ramifications of a dysfunction of this system with respect to stress
      related or exacerbated disorders such as post-traumatic stress disorder and
      schizophrenia.

PMID- 8978989
TI  - A functional neuroanatomy of anxiety and fear: implications for the
      pathophysiology and treatment of anxiety disorders.
AB  - This paper reviews the evidence that provides the basis for a functional
      neuroanatomy of anxiety and fear. The afferent arm of the anxiety circuit
      includes the exteroceptive sensory systems of the brain, which convey the sensory
      information contained in a fear- or anxiety-inducing stimulus to the dorsal
      thalamus. Visceral afferent pathways alter the function of the locus coeruleus
      and the amygdala. The thalamus relays sensory information to the primary sensory
      receptive areas of the cortex, which project to adjacent unimodal and polymodal
      cortical association areas. The cortical association areas send projections to
      the amygdala, entorhinal cortex, orbitofrontal cortex, and cingulate gyrus. A
      pivotal role for the amygdala in the transmission and interpretation of fear and
      anxiety is suggested by extensive afferents to the amygdala from thalamic and
      cortical exteroceptive systems, as well as by subcortical visceral afferent
      pathways. The neuronal interactions between the amygdala enable the individual to
      initiate adaptive behaviors to threat based upon the nature of the threat and
      prior experience. The efferent pathways involving the amygdala, locus coeruleus,
      hypothalamus, periaqueductal gray, and striatum mediate autonomic,
      neuroendocrine, and skeletal-motor responses associated with fear and anxiety.
      The proposed brain structures, neural mechanisms, and neural circuits related to
      anxiety provide a basis for increased understanding of the pathophysiology of
      anxiety disorders.

PMID- 8978990
TI  - Lessons from angiotensin-converting enzyme-deficient mice.

PMID- 8978991
TI  - Haemodynamically mediated glomerular injury: the end of a 15-year-old
      controversy?

PMID- 8978992
TI  - Survival with end-stage renal failure in the 1990s.

PMID- 8978993
TI  - Renal replacement therapy in acute renal failure.
AB  - The choices regarding renal replacement therapy in acute renal failure have
      become more complex. The underlying prognosis of the patient should be considered
      when making the choice of a dialysis treatment. The attending nephrologist must
      also have a working knowledge of the potential advantages of various dialyzers
      and continuous renal replacement therapies to maximize the potential for recovery
      of patients with acute renal failure.

PMID- 8978994
TI  - Hemodialysis vascular access: emerging concepts.
AB  - Vascular access complications remain a leading cause of morbidity and
      hospitalization in patients on chronic maintenance hemodialysis. Although
      arteriovenous fistulas remain the dialysis access of choice, an increasing
      percentage of patients are dialyzed using synthetic grafts or permanent
      catheters. The most frequent vascular access complications are the development of
      stenosis and of thrombosis. In recent years, increasing attention is being paid
      to screening techniques designed to detect vascular access stenosis prior to
      thrombosis. Aggressive screening techniques coupled with interventional
      procedures such as angioplasty may reduce the incidence of graft thrombosis. Once
      thrombosis has occurred, mechanical or pharmacomechanical thrombolysis in
      conjunction with angioplasty may be an effective alternative to surgical
      thrombectomy.

PMID- 8978995
TI  - Adequacy of peritoneal dialysis.
AB  - Landmark studies relevant to the adequacy of peritoneal dialysis have recently
      been published. The Canada/USA peritoneal dialysis study has shown a relationship
      between clearance indices and patient survival rate, but the study is confounded
      by residual renal function. Registry data show conflicting results concerning
      survival rates on peritoneal dialysis and haemodialysis. The complicated
      pathogenesis of malnutrition in dialysis patients is now becoming further
      appreciated.

PMID- 8978996
TI  - Hepatitis C in dialysis and transplantation.
AB  - The identification of the hepatitis C virus as the major cause of liver disease
      both in dialysis patients and in transplant patients has focused attention on the
      epidemiology and the impact of continuing infection in these patient groups. The
      present understanding of transmission, the extent of liver injury, the influence
      on outcome measures and treatment has grown substantially in a relatively short
      time.

PMID- 8978997
TI  - Update on the status of pancreas-kidney transplantation.
AB  - Patient and graft survival rates after combined kidney and pancreas
      transplantation continue to improve. Percutaneous and cystoscopic pancreas
      biopsies are safe and aid in the diagnosis of acute rejection. Primary enteric
      drainage of pancreatic exocrine secretions is being re-evaluated to avoid the
      morbidity associated with bladder drainage. The use of FK506 might reduce the
      number of acute rejection episodes with no diabetogenic side effects. More
      studies have been presented which demonstrate that pancreas transplantation might
      improve diabetic microangiopathy and polyneuropathy and protect the transplanted
      kidney from diabetic nephropathy.

PMID- 8978998
TI  - Mycophenolate mofetil in kidney transplantation.
AB  - Mycophenolate mofetil is a new immunosuppressive agent recently released for
      clinical use, in conjunction with steroids and cyclosporine, for the prevention
      of acute rejection in renal transplant patients. It inhibits the enzyme inosine
      monophosphate dehydrogenase, which is essential for de-novo synthesis of guanine
      nucleotides. The result is lymphocyte-selective arrest of cell division, with
      little effect on other tissues. In clinical trials in renal transplant, its
      efficacy and safety have been established: mycophenolate mofetil reduces acute
      rejection episodes by approximately 50%, with the principal toxicity being
      gastrointestinal, and perhaps some increase in cytomegalovirus infection.
      Overall, mycophenolate mofetil (plus cyclosporine and steroids) has a toxicity
      profile similar to that of azathioprine but with considerably increased efficacy.
      Despite its cost, mycophenolate mofetil is likely to be used in many renal
      transplant centres to reduce acute rejection, especially in the first year.
      Future trials are necessary to establish its long-term role in renal
      transplantation and its usefulness in the transplantation of other organs.

PMID- 8978999
TI  - Xenotransplantation.
AB  - Xenotransplantation of pig organs into humans represents an attractive solution
      to the worldwide organ shortage. The survival of pig organs in primates has so
      far primarily been hampered by hyperacute rejection of the xenograft. The
      immunological mechanisms which underlie hyperacute rejection have recently been
      clarified. These important elucidations, together with the introduction of
      genetic engineering in the field of transplantation, have led to the production
      of genetically manipulated animals with organs that are now not susceptible to
      the immunological factors responsible for hyperacute rejection. In this article
      the recent advances in the understanding of hyperacute rejection are reviewed and
      the latest biomolecular approaches to overcome hyperacute rejection are
      described.

PMID- 8979000
TI  - Renal diagnostic testing: past, present and future.

PMID- 8979001
TI  - Measuring the adequacy of peritoneal dialysis: is there a link with nutrition and
      outcome?
AB  - Adequacy of peritoneal dialysis is predictive of outcome but the absolute
      evidence for setting optimal levels or targets is still lacking. The link between
      adequacy and nutrition is also tenuous and appears to be based on a mathematical
      relationship. The ability of standard continuous ambulatory peritoneal dialysis
      regimes to provide adequate dialysis may be limited in anuria and in large
      individuals.

PMID- 8979003
TI  - Screening for cardiovascular disease in dialysis patients.
AB  - The burden of cardiac disease in dialysis patients is high, resulting from
      cardiomyopathy and from coronary artery disease. Asymptomatic dialysis patients,
      patients with heart failure, patients with symptomatic ischaemic heart disease,
      and patients being evaluated for renal transplantation all require investigation
      to determine the presence or the extent of heart disease. Echocardiography is
      very useful for screening for cardiomyopathy, but should be undertaken when
      patients are euvolaemic. Non-invasive tests for coronary artery disease,
      particularly exercise-based tests, are less sensitive and less specific in
      dialysis patients than in the general population. Dobutamine stress
      echocardiography may be more sensitive in patients with renal failure than other
      investigations. Patients with abnormal screening tests or symptomatic ischaemic
      heart disease should undergo coronary angiography and subsequent
      revascularization procedures if indicated.

PMID- 8979002
TI  - Measuring the adequacy of hemodialysis access.
AB  - Vascular access morbidity is still an important problem. The risk of thrombosis
      increases in prosthetic grafts as the access flow decreases below 600 ml/min,
      whereas native arteriovenous accesses can maintain patency at much lower flows,
      in some cases flows below those needed to deliver adequate dialysis. Intra-access
      pressures are also dissipated differently in the two access types. These
      differences between native and prosthetic grafts determine the utility of the
      monitoring techniques that are useful for detecting stenosis and assessing
      function in the two access types. Modern non-urea methods for measuring access
      recirculation are therefore useful in native but not in graft hemoaccesses.
      Direct or indirect intra-access pressure measurements and direct flow
      measurements are most useful in grafts to detect and then correct lesion before
      thrombosis.

PMID- 8979004
TI  - Radiographic evaluation of the renal vasculature.
AB  - Renal artery stenosis is an important cause of hypertension and progressive renal
      insufficiency. Additionally, there is increasing concern that renovascular
      disease is a significant, but previously-unrecognized, cause of end-stage renal
      disease in certain subsets of patients. Advances in revascularization techniques
      offer a greater opportunity for blood pressure control and for the restoration or
      preservation of renal function. Accurate imaging of the renal vasculature,
      however, is essential for the proper selection of those individuals who might
      best benefit from such intervention. Although conventional or digital subtraction
      arteriography remains the gold standard diagnostic test, significant advances in
      non-invasive imaging techniques now offer the clinician several options for the
      accurate diagnosis of hemodynamically significant renovascular disease. These
      techniques include captopril renography, duplex ultrasonography, magnetic
      resonance angiography, and spiral/fast computed tomography. In this review, the
      advantages and limitations of these imaging techniques are compared and
      contrasted with an emphasis on their usefulness in screening for renovascular
      disease. Also reviewed are recent applications of these techniques for
      measurement of renal function, predicting outcome of revascularization, and the
      clinical monitoring of patients with renovascular disease managed either
      medically or by revascularization.

PMID- 8979005
TI  - The role of angiotensin I-converting enzyme gene polymorphism in renal disease.
AB  - Some renal diseases (e.g. diabetic nephropathy and IgA glomerulonephritis)
      cluster within families, consistent with a strong genetic component for the
      development or progression of these diseases, or both. In this context it is
      attractive to examine the insertion/deletion polymorphism of the angiotensin I
      converting enzyme. This polymorphism determines the concentration of angiotensin
      I-converting enzyme not only in serum, but also in tissues and thereby presumably
      the locally available concentration of angiotensin II. Several studies have
      examined whether this polymorphism is associated with the development of diabetic
      nephropathy, but most of these failed to show such an association. Studies in
      patients suffering from IgA glomerulonephritis or other renal diseases, including
      diabetic nephropathy, demonstrated that the insertion/ deletion polymorphism
      plays a role in the progression of renal diseases and in the response to
      treatment with angiotensin I-converting enzyme inhibitor.

PMID- 8979006
TI  - Dialysis and transplantation.

PMID- 8979007
TI  - Diagnostics and techniques.

PMID- 8979008
TI  - General obstetrics--prevention: the perinatal medicine of the future.

PMID- 8979009
TI  - Folic acid to prevent neural tube defects: scientific advances and public health
      issues.
AB  - Folic acid prevents some neural tube defects by correcting abnormal homocysteine
      metabolism. A defective gene coding for a homocysteine-related enzyme has been
      shown in people with neural tube defects. An extensive educational campaign will
      be required to alert women to the need to take 0.4 mg/day of folic acid during
      their childbearing years.

PMID- 8979010
TI  - Medications in pregnancy.
AB  - Chronic medical problems and the various medications available to treat them
      represent an enormous volume of information for the practicing obstetrician. The
      agents commonly encountered are reviewed here and current literature is explored,
      where available, including the literature on folates in pregnancy.

PMID- 8979011
TI  - Adverse consequences of prenatal illicit drug exposure.
AB  - Our appreciation of the impact on health of illicit drug use is growing. Once
      considered a maternal risk, prenatal drug exposure may target fetal
      neurobehavior, affecting attention and learning as the child grows into
      adulthood. Cocaine, opiates, marijuana, and amphetamines have each been
      scrutinized for adverse actions on placental transport, fetal behavior states,
      newborn withdrawal, and childhood learning and attentive skills. Neurotransmitter
      analysis in the animal model after prenatal drug exposure now provides biological
      support for these clinical findings. The increasing prevalence of drug use by
      pregnant women, the effect of illicit drug use on transmission of the human
      immunodeficiency virus, and the maternal and fetal consequences of illicit drug
      exposure make illicit drug use in pregnancy a central challenge in maternal-fetal
      medicine and a need-to-know field in general obstetrics.

PMID- 8979012
TI  - Congenital malformations.
AB  - Obstetricians' epidemiological knowledge and their awareness of associated risk
      factors are essential for the primary prevention of birth defects. Screening and
      early diagnosis of congenital malformations is an expanding field in general
      obstetrics. Cardiac defects are the most frequent type of congenital
      malformation, and early detection is possible.

PMID- 8979013
TI  - Prediction of prematurity.
AB  - Preterm birth is the leading cause of perinatal morbidity and mortality. A poor
      understanding of the underlying pathophysiology of spontaneous preterm labor and
      preterm premature rupture of membranes has limited our ability to identify those
      women at highest risk for spontaneous preterm birth. There is increasing evidence
      that inflammation of the upper genital tract may play a major role in the
      pathogenesis of preterm labor and preterm premature rupture of membranes. Newer
      markers of infection and inflammation (e.g. bacterial vaginosis, fetal
      fibronectin, interleukin-6) may make earlier diagnosis possible and may direct
      potential therapeutic interventions. A better understanding and more accurate
      diagnosis of well known risk factors (e.g. cervical dilatation) may also improve
      treatment options. Additionally, combinations of older risk factors and newer,
      more sensitive diagnostic methods may greatly increase our ability to predict
      preterm birth and to identify women who might benefit most from directed
      intervention strategies.

PMID- 8979014
TI  - Infection and prematurity: evidence-based approaches.
AB  - The real cost savings arising from effectively preventing or treating preterm
      birth ascribable to prevalent reproductive tract infections are demonstrated in
      the lives of children saved from premature death and personal, biologic and
      economic impairment. Three meta-analyses demonstrate neonatal and maternal
      benefits from adjunctive antibiotic treatment of mothers suffering preterm
      premature rupture of membranes. The effects of adjunctive antibiotic treatment of
      women with preterm labor are inconsistent, but single-agent regimens using
      erythromycin and clindamycin are effective and provide coverage for group B
      streptococcus. Providers and payers now have evidence-based, clinically proven
      and cost-saving opportunities to prevent important numbers of preterm births, as
      well as preventing individual children suffering from being 'born too soon'.

PMID- 8979015
TI  - Pregnancy hypertension and uterine artery Doppler ultrasound.
AB  - The application of uterine artery Doppler velocimetry as a screening test for pre
      eclampsia and other adverse pregnancy complications is still considered a
      research tool by most obstetricians. Increasing use of colour Doppler ultrasound
      has allowed a better understanding of pathophysiological changes in the uterine
      circulation. This in turn has refocused attention on the potential use of uterine
      artery Doppler velocimetry as part of our antenatal screening strategy. This
      review summarizes the most recent work surrounding the application of this test
      as a screening test for pre-eclampsia.

PMID- 8979016
TI  - Pre-term pre-labour amniorrhexis.
AB  - In pregnancies complicated by pre-term pre-labour aminorrhexis, there is a risk
      of intra-uterine infection, which is associated with maternal and perinatal
      mortality and morbidity. The causes of neonatal death in pregnancies with
      aminorrhexis are prematurity, pulmonary hypoplasia and sepsis. In the management
      of pregnancies with pre-term pre-labour amniorrhexis, it is essential to
      distinguish between those with and without intra-uterine infection. If there is
      no infection at presentation, it is unlikely that this will develop, and in such
      cases there is no benefit from hospitalization, bed rest, prophylactic tocolytics
      or antibiotics. The group with evidence of intra-uterine infection go into
      spontaneous labour within a few days of amniorrhexis; in this group, the main
      determinant for the appropriate management is the gestational age at
      amniorrhexis.

PMID- 8979017
TI  - Recurrent second trimester miscarriage.
AB  - Understanding the aetiology of a second trimester miscarriage allows the
      obstetrician to assess the recurrence risk in the next pregnancy and guides
      future management. Causes include anatomical abnormalities, cervical
      incompetence, genital tract infection, multiple pregnancy, auto-immune factors,
      vaginal bleeding, and fetal abnormalities. Transvaginal ultrasound of the cervix
      in pregnancy may have a role in the diagnosis of cervical incompetence. There is
      an association between genital tract infection and second trimester miscarriage,
      but the value of antibiotics in the prevention of miscarriage is still to be
      defined.

PMID- 8979018
TI  - Human immunodeficiency virus and pregnancy.
AB  - There are now proven ways to reduce the transmission of human immunodeficiency
      virus from infected mothers to their offspring, including the use of zidovudine
      during pregnancy and labour, and avoidance of breast-feeding. Therefore,
      screening programmes should be extended to enable at-risk mothers to benefit from
      these advances.

PMID- 8979019
TI  - Thromboembolism in pregnancy: an overview.
AB  - Thromboembolism is a major cause of maternal mortality. Recent advances in the
      management of thromboembolism in pregnancy include the discovery of a new,
      inherited thrombophilia, an improved understanding of the indications for
      thromboprophylaxis, and the increased use of low-molecular-weight heparin instead
      of unfractionated heparin.

PMID- 8979020
TI  - A case of premature menopause in an ovulating 46,XY female patient.

PMID- 8979021
TI  - CD34 progenitor cell subset analyses in normal human bone marrow and marrow
      harvested after intermediate-dose chemotherapy.
AB  - Previous attempts to characterize harvested marrow and peripheral blood stem cell
      (PBSC) in order to predict time to and quality of engraftment post autologous
      bone marrow transplant (autoBMT) have included use of in vitro colony forming
      unit (CFU) assays. These assays are hampered by interlaboratory variability and
      are not uniformly predictive. CD34 quantification by flow cytometric technique
      has also been used to assess the quality of harvested marrow and PBSC. However, a
      lack of standardization has hampered direct comparison of published reports. We
      sought to characterize these early lineage-committed CD34+ progenitor cells from
      non-ficolled harvested marrow with six progenitor cell (PC) panels containing
      CD34 antibody plus two additional early lineage markers, using multiparameter
      flow cytometry. The specific gating technique including simultaneous CD34-PE vs.
      side scatter and forward vs. side scatter, was verified using morphologic
      analyses of sorted CD34+ cells. An ungated file was initially acquired to assess
      total CD34+ content. A second file using a CD34 threshold was then acquired to
      resolve lineage-committed subsets. The % CD34+ cells as well as cells/microliter
      of bone marrow was calculated using cell counts at the time of marrow harvest.
      Bone marrow (mean total cell dose = 3.8 x 10(5)/kg), obtained from 42 normal
      donors for allogeneic transplantation was first analyzed. CD34+ cells comprised a
      mean 1.3% of non-ficolled marrow, with 328 CD34+ cells/microliter, and mean CD34+
      cells collected was 4.8 x 10(6)/kg. While no significant differences in total
      cells harvested nor proportion of CD34+ cells was found, a significant decrease
      in CD34 cells/microliter (= 233, P = .0012) was found in cancer patients. The
      percentage of CD19+ and CD38+ progenitor cells was significantly increased, while
      CD5+ and CD71+ cells were decreased. The proportions of all other early lineage
      committed CD34 subsets were not different. Measurement of lineage-committed CD34
      progenitor cells is a useful technique to characterize harvested marrow and PBSC,
      and may be applied to predict time and quality of engraftment post ablative
      conditioning regimens.

PMID- 8979022
TI  - Flow cytometric analysis of kappa and lambda light chain expression in evaluation
      of specimens for B-cell neoplasia.
AB  - Analysis of light chain expression is one of the most important determinations in
      flow cytometric immunophenotyping of patient specimens. Numerous technical
      factors, such as antibody choice and cytophilic antibody artifact, impact a
      laboratory's ability to perform this test. There have been conflicting reports
      concerning the efficacy of polyclonal versus monoclonal antibodies, as well as
      methods of circumventing cytophilic antibodies, indicating that a consensus has
      not been reached on optimal methods for light chain determination. The authors
      have investigated methods for light chain analysis in 104 normal donors and 366
      patient specimens, comparing different anti-light chain antibodies as well as
      strategies for analysis of specimens with low numbers of monoclonal B cells,
      admixed polyclonal B cells, or cytophilic antibodies. The patient specimens were
      either part of the initial diagnostic evaluation of patients with suspected
      lymphoma, or were performed for staging or assessment of treatment of patients
      with known B-cell neoplasia. No monoclonality was detected in control specimens,
      and there was no significant difference in staining with monoclonal verses
      polyclonal anti-light chain antibodies. In addition, cytophilic antibody did not
      obscure results in normal controls. Monoclonality was detected in 106 patient
      specimens, with 89 showing gross involvement with a predominant monoclonal B-cell
      process. However, in 43% of the grossly monoclonal specimens, there was failure
      to detect monoclonality with at least one light chain antibody set, with 8% of
      these cases showing failure with two anti-light chain sets. This indicates the
      importance of antibody choice in light chain analysis. Cytophilic antibody
      artifact in monoclonal specimens was easily overcome by appropriate antibody
      combinations, obviating the need for cytophilic antibody-shedding by incubation
      at 37 degrees C in fetal calf serum. In 27 patient specimens with low numbers of
      B cells or admixed polyclonal B cells, a clonal search based on FSC and CD19 or
      CD20 expression was performed. In 17 of the 27 cases (63%), a small monoclonal
      population was detected among admixed polyclonal B cells. The authors conclude
      that multiple strategies are necessary in flow cytometric analysis for B-cell
      monoclonality.

PMID- 8979023
TI  - DNA ploidy and protein content in bronchioloalveolar carcinoma multi-variable
      flow cytometry.
AB  - Multi-variable flow cytometry studies were done on paraffin-embedded surgical
      specimens from 97 patients with bronchiolalveolar carcinoma (BAC) and on 10
      normal lung tissue specimens to assess the value of nuclear protein content
      besides DNA ploidy. Tumor tissues were stained for DNA content with propidium
      iodide and for protein content with fluorescein isothiocyanate. DNA ploidy
      measurements were successful in 87 of the 97 specimens. Twenty-four (28%)
      specimens were DNA diploid, and 63 (72%) were DNA nondiploid (DNA tetraploid or
      DNA aneuploid). There was no significant difference in survival between patients
      with DNA diploid and with DNA nondiploid tumors (P = 0.69). The protein histogram
      pattern was bimodal in 26/87 (30%) of patients; these had significantly shorter
      survival than patients with either normal or right-shift protein histogram
      patterns (61/87) (P = 0.0033). The nuclear protein measurement was an independent
      prognostic indicator when corrected for tumor grade and tumor size in a Cox model
      analysis (P = 0.04). The nuclear protein measurement correlated with nuclear size
      as determined by nuclear volume measurements. The combination of DNA ploidy,
      protein, and cell size measurements by flow cytometry provide a useful biologic
      basis for the variable prognosis seen with BAC tumors.

PMID- 8979024
TI  - Quantification of CD1a, HLA-DR, and HLA class I expression on viable human
      Langerhans cells and keratinocytes.
AB  - In order to determine precisely the cellular density of surface molecules that
      are critical for antigen presentation in human epidermis, we utilized a
      quantitative immunofluorescence indirect assay and performed flow cytometric
      analysis of human epidermal cell (EC) suspensions. We first demonstrated that
      Tricolor-labeled streptavidin coupled to Cy-5 (SA-TC) was a reliable marker for
      non viable EC and that SA-TC+ EC accounted for the frequent nonspecific
      background of fluorescence due to isotype controls binding, although Langerhans
      cells (LC) and Keratinocytes (Kc) express Fc receptors for IgG on their surfaces.
      These results indicate that quantification of cell surface antigens on human EC
      requires the concomitant use of a marker of viability. Multicolor flow cytometric
      analysis allowed us to quantify CD1 molecules and major histocompatibility
      complex (MHC) antigens on viable human LC and Kc. Our results demonstrated a weak
      expression of MHC class I molecules on viable LC (163 +/- 19 x 10(3)
      molecules/cell) compared to viable Kc (785 +/- 110 x 10(3) molecules/cell). Mean
      antigen density of HLA-DR and CD1a molecules on viable LC were 579 +/- 82 x 10(3)
      molecules/cell and 1600 +/- 133 x 10(3) molecules/cell, respectively.
      Quantitative flow cytometry of viable EC may be proposed to evaluate the number
      of membrane antigens whose level of expression is related to cellular maturation
      or activation that occurs in skin diseases.

PMID- 8979025
TI  - Quantitative determination of surface antibody binding capacities of immune
      subsets present in peripheral blood of healthy adult donors.
AB  - The objective of this study was to quantitate the antibody binding capacity (ABC)
      of CD3, CD4, CD8, CD16, and CD19 on lymphocytes and CD4 on monocytes from healthy
      adult donors. Peripheral blood was collected over three consecutive days and
      repeated in the same format two weeks later for comparison to initial
      measurements. Immune subsets were labeled by direct single or two-color staining
      in whole blood followed by lysis of erythrocytes. Fluorescence intensity
      measurements were made by carefully calibrating the flow cytometer and then
      measuring the intensity of monoclonal antibody staining on labeled cells and on
      Quantum Simply Cellular Microbeads. The effect of paraformaldehyde fixation on
      intensity measurements and coefficient of variation of thirty replicates for each
      phenotype were also studied. We found a small change in calculated ABC following
      overnight fixation with a greater change following 48 h of fixation prior to flow
      cytometric analysis. We found excellent precision could be achieved for measuring
      the ABC of most markers with some improvement desirable for expression of CD4 on
      monocytes and CD16+ lymphocytes. Between donors we found a high-low range of CD3+
      = 134,349-45,905; CD4+ (lymphocytes) = 54,174-36,106; CD4+ (monocytes) = 9,246
      3094; CD8+ = 268,868-190,622; CD3+CD8+ = 269,858-212,024; CD16+ = 38,307-336; and
      CD19+ = 25,252-11,689. For the total donor group, the observations at week 1 and
      week 2 were not significantly different (alpha = .05) for any of the
      immunophenotypes we studied. The data presented here continue to show that it is
      possible to perform quantitative intensity measurements of immune subsets when
      performing immunophenotyping studies.

PMID- 8979026
TI  - Long lasting immunological effects of ethanol after withdrawal.
AB  - The aim of the present study was to analyze on chronic alcoholic patients the
      effect of ethanol (EtOH) withdrawal on the immune system through the
      investigation of the distribution of PB lymphoid subsets, using multiple
      stainings with monoclonal antibodies and flow cytometry. For this purpose a group
      of 20 patients with active alcoholism without liver disease, negative for
      hepatitis virus, and without malnutrition was analyzed and followed for 9 months
      after alcohol consumption had been discontinued. Twenty-five age- and sex-matched
      healthy volunteers were included in the study. The following panel of monoclonal
      antibodies combinations (FITC/PE/PerCP or PE-Cy5) was used: TCR alpha
      beta/CD3/HLA DR, CD25/CD56/CD3, TCR gamma delta/CD3/HLA DR, CD45RA/CD45R0/CD4,
      CD3/CD8, CD19/CD5, and CD3/CD11c. Analysis was performed on at least 1,500
      events/tube at flow cytometry using the Lysys II software program. During the
      alcohol intake period, the most striking findings were a significant (P < 0.05)
      expansion of the CD8+ T-lymphocyte subset, which coexpresses the activation
      associated antigens HLA DR and CD11c, as well as a significant increase in both
      NK-cells (CD3-/CD56+) and the T-cell subset with NK activity coexpressing CD3 and
      CD56 (P < 0.05 and P < 0.01, respectively). In addition, a decrease in the CD5+ B
      cells (P < 0.05), associated with reduced serum gamma-globulin levels, was also
      observed. During alcohol withdrawal, a rapid decrease towards normal values of
      activated CD8+/HLA DR+ and CD11c+ T-lymphocytes was observed as well as a
      normalization of CD19+/CD5+ B-cells and gamma-globulin serum levels; these
      changes might be directly related to EtOH suppression. Surprisingly, however, new
      immunological imbalances emerged in spite of the absence of alcohol intake. Thus,
      a progressive and significant expansion (P < 0.05) of CD4+ T-cells associated
      with an increased expression of the CD25 activation-related antigen and a
      preferential use of the CD45R0 isoform by CD4+ T-cells were observed. In
      parallel, there was an even more evident increase (P < 0.01) in the number of PB
      NK-cells. Our results show that EtOH consumption induces changes in the immune
      system, its effects persisting or even becoming more evident after suppression of
      EtOH intake for a 9 month period.

PMID- 8979027
TI  - Association between flow cytometric S-phase fraction and apoptotic rate in breast
      cancer.
AB  - Tumor heterogeneity may adversely affect the flow cytometric measurement of S
      phase fraction (SPF) in breast cancer specimens, and 10-20% of breast cancer
      specimens are not evaluable by flow cytometry due to technical factors such as
      debris, high coefficients of variation, poor specimen quality, or small sample
      size. Therefore, we performed this study on 207 specimens of breast cancer in
      order to determine if the apoptotic rate (AR) could serve as a useful adjunct to
      flow cytometric SPF measurements in breast cancers. The average AR in each
      specimen was determined by microscopic examination of tumor tissue that was
      specifically stained for apoptotic bodies by a commercially available TUNEL (Tdt
      mediated dUTP digoxigenin nick end labelling) assay kit. The mean AR (4.5 +/-
      3.0, n = 37) in the high SPF (> 10%) group was significantly (P < 0.01) higher
      than the mean AR (1.3 +/- 1.2, n = 72) in the low SPF (< 6%) group. Although the
      distributions of AR values in the two groups had substantial overlap, AR values
      greater than 5.5 per high power field (h.p.f.) were not observed in the low SPF
      cases but were present in 13 out of 37 cases with a high SPF. Simple linear
      regression analyses relating SPF to the mean AR in 57 DNA diploid cases and 41
      DNA aneuploid cases yielded a minimal correlation (r2 = 0.21) between the two
      parameters only in the DNA aneuploid group. We conclude that an elevated AR has
      an association with high SPF in breast cancers, but the association is too weak
      to permit the general use of AR as a predictor of SPF. Our study also identified
      a subset of breast cancers with both a high SPF (> 10%) and a high AR (>
      5.5/h.p.f.) that may warrant further investigation to determine its clinical
      significance.

PMID- 8979028
TI  - Flow cytometric HLA-B27 typing using CD3 gating and molecules of equivalent
      soluble fluorochrome (MESF) quantitation.
AB  - The determination of HLA-B27 (B27) status is important in the diagnosis of
      ankylosing spondylitis, Reiter's disease, and other arthropathies. Flow
      cytometric (FCM) typing of B27 is a relatively new method which allows for rapid
      turnaround time and low cost. However, different leukocyte populations may
      manifest significant variation in staining intensity with B27 antibodies.
      Therefore, gating utilizing only light scatter properties of cells may lead to
      high readings in some B27-negative samples. Fluorescence gating on CD3+ cells
      were postulated as a means to eliminate these anomalies. Furthermore,
      quantitative FCM measurements, as afforded through use of molecules of equivalent
      soluble fluorochrome (MESF) units, can minimize day-to-day and instrument-to
      instrument variabilities in fluorescence measurements. We compared CD3 gating to
      light scatter gating and MESF analysis on 123 specimens in a 4-month period and
      found: 1) CD3 gating gave the lowest nonspecific B27 antibody binding among B27
      negative subjects; 2) there was no significant difference in MESF values between
      CD3 gating and light scatter gating of B27-positive samples; 3) there was a wide
      range of B27 antibody binding fluorescence intensities among B27-positive
      subjects; 4) identification of patients with low B27 expression may require the
      use of CD3 gating in order to avoid costly confirmation testing; 5) fluorescent
      standard beads are stable for routine use in a clinical flow cytometry
      laboratory.

PMID- 8979029
TI  - DNA-ploidy studies on cytological preparations from breast cancers by image
      analysis: comparison with Feulgen staining performed in destained Papanicolaou
      slides.
AB  - Image cytometric analysis of DNA ploidy status of 40 fresh primary breast
      carcinomas was performed in a comparative study on cytologic preparations stained
      directly by the Feulgen method and smears from the same tumors Feulgen-stained
      after Papanicolaou staining. There was a 0.82 overall concordance in diploid and
      aneuploid tumor classification and a good correlation (r = 0.736, P < 0.001)
      between the DNA indices determined by the two methods. Discordances are probably
      due to tumor heterogeneity. This study demonstrates that image cytometric DNA
      analysis on previously routine-stained cytologic preparations is feasible and
      reliable for pretreatment DNA analysis and suggests potential applications in
      retrospective studies with cytologic material from archives.

PMID- 8979030
TI  - Automated assessment of numerical chromosomal aberrations in paraffin embedded
      prostate tumor cells stained by in situ hybridization.
AB  - We investigated the feasibility of automated counting of in situ hybridization
      signals (ISH) in interphase cells isolated from paraffin embedded prostate
      tissue. In total, 34 specimens from 7 patients with prostate cancer were stained
      with probes specific for the centromeric regions of chromosomes Y, 1, 7, 8, 10,
      and 15, using an immunoperoxidase based technique suitable for bright-field
      microscopy. Enumeration of the number of ISH spots of 500 nuclei per specimen was
      performed (1) using an automatic system developed without any human intervention
      and (2) using the same system, but including verification of the counts based on
      visual inspection of the stored images. As reference from each specimen, 200 cell
      nuclei were evaluated manually, using conventional microscopy. A typical analysis
      procedure (including user verification) took 35 min. The difference (root mean
      error) between the automated counting and the counting after visual interaction
      was relatively small (15%). The percentage of cells with incorrect counts by
      automated analysis was 20.2%, a number that could easily be improved by user
      interaction. Detection of cells with aneusomy proved to be more sensitive
      compared to the routine manual counting, in cases where aberrant frequencies were
      low. Automated counting of samples with low frequencies (< 10%) resulted in a
      higher frequency of aberrant cells in 9 of 11 cases, probably due to the fact
      that an unbiased cell selection is guaranteed. Automated assessment of ISH
      signals is considered useful for the evaluation of chromosomal aberrations in
      prostate tumor cells, provided that the counts are visually confirmed.

PMID- 8979032
TI  - Enhanced flow cytometric method for counting very low numbers of white cells in
      platelet products.
AB  - BACKGROUND: The increased demand for leukocyte-reduced platelet products has
      prompted actions both by blood suppliers and device manufacturers to develop
      effective quality assurance methods and improved devices for leukocyte-reduced
      platelet preparation. White cell (WBC) counting methods capable of counting WBCs
      substantially below 1,000 WBC/mL enhance these activities. The purpose of this
      study was to enhance and validate a method capable of counting 5-10 WBC/mL in
      platelets. METHODS: We added marker chicken red blood cells (cRBC) at a known
      concentration to an aliquot of platelet concentrate containing propidium iodide
      stain solution (PI). A modified BD FACScan was used to analyze this mixture. The
      ratio of cRBC and WBC events observed was used with the cRBC concentration to
      calculate the WBC concentration. Validation was performed by analyzing standard
      curves prepared with leukocyte-depleted platelet diluent. Methods of preparing
      leukocyte-reduced platelets by apheresis and filtration were evaluated using this
      method. RESULTS: The method was linear from 5,000 WBC/mL to 10 WBC/mL (r2 =
      0.983). Residual WBCs in the platelet diluent hampered validation below 10
      WBC/mL. Repeatability (CV) was 44% at 8 WBC/mL and 6.5% at 1,000 WBC/mL. The
      FACScan required frequent mixing of the sample and flushing with cleaning agents
      during acquisition. CONCLUSIONS: This method has good linearity and
      reproducibility from 10-5,000 WBC/mL for platelets. It is suited for research and
      development work, and may be a useful adjunct method for quality assurance in the
      blood center.

PMID- 8979031
TI  - Measurement of T-cell CD69 expression: a rapid and efficient means to assess
      mitogen- or antigen-induced proliferative capacity in normals.
AB  - We have analyzed the expression of the activation antigen CD69 on normal human T
      cells by flow cytometry following stimulation with mitogens and recall antigen.
      These data were compared to parallel studies assessing the proliferative response
      using the 3H-thymidine (3H-TdR) incorporation assay. Three different mitogens
      (PHA, ConA, and CD2/CD2R) induced maximal expression of CD69 at 24 h, which
      remained stable throughout the 72 h culture period. The mitogen-stimulated cells
      initiated DNA synthesis as determined by the 3H-TdR assay (72 h) while
      nonstimulated cells failed to upregulate CD69 or incorporate 3H-TdR. We next
      compared T cell CD69 expression (n = 12) following stimulation with either
      CD2/CD2R (5 micrograms/ml) or the recall antigen, tetanus toxoid (1:1500). Cell
      proliferation was determined by the 3H-TdR assay at 72 h (CD2/CD2R) or 120 h
      (tetanus toxoid). Evaluation of CD69 expression at 6 h predicted CD2/CD2R but not
      tetanus responder status as defined by 3H-TdR incorporation. However, when 4
      known tetanus responders (3H-TdR) were evaluated over time, it was found that at
      48 h the fluorescence intensity (of CD69) on tetanus-stimulated CD3+ cells
      increased markedly compared with nonstimulated cells (range of increase 43-850%).
      One individual whose cells failed to respond to tetanus toxoid (3H-TdR and CD69)
      did respond normally to CD2/CD2R. These observations suggest that flow cytometric
      evaluation of T cell CD69 expression following mitogen (6 h) or antigen (48 h)
      stimulation may provide an accurate screen of T-cell responsiveness in normals.

PMID- 8979033
TI  - Apoptosis of cells in aged samples as detected by the ProCOUNT reagent.
AB  - An unusual population of high side scatter, low nucleic acid dye binding, dim
      CD45 cells was found in aged blood samples stained with the ProCOUNT reagent.
      Cell surface staining showed that these cells have the surface phenotype of
      neutrophils. However, they have decreased expression of several surface antigens,
      bind annexin V, and stain more dimly than normal neutrophils with LDS-751. These
      characteristics indicate that the cells have become apoptotic. The decreased
      expression of the CD45 antigen on apoptotic neutrophils could have an impact on
      some methods for enumerating CD34-positive progenitor cells. Absolute CD34
      positive cell counts are frequently obtained by multiplying CD34-positive cells
      as a percentage of the total cells by the white blood cell count from a
      hematologyanalyzer. Cells staining dimly with CD45 may not pass a flow cytometer
      threshold set on this parameter but appear to be detected by a hematology
      instrument thresholding on cell size. Thus the white blood cell counts from the
      two sources may not be identical, introducing error into the calculated absolute
      CD34 count. Absolute counts of CD34 cells based on simultaneous acquisition of a
      counting bead are not affected by the presence of this population, but purity
      estimates can be affected if the possible presence of these cells is not
      considered in aged samples.

PMID- 8979034
TI  - Preliminary observations on the development of auditory sensitivity in infants
      with Down syndrome.
AB  - OBJECTIVE: Hearing loss commonly is associated with Down syndrome, but little is
      known about the development of auditory sensitivity in individuals with Down
      syndrome. This study had two objectives: 1) to determine whether an observer
      based procedure can be used to assess the behavioral sensitivity of infants with
      Down syndrome, and 2) to provide preliminary information about the early course
      of hearing development among infants with Down syndrome. DESIGN: Behavioral
      measures of sensitivity were made in 16 infants with Down syndrome using an
      observer-based procedure. Ten of the infants were followed longitudinally between
      2 and 12 mo of age. All infants passed a screening auditory brain stem response
      at 20 dB nHL during the study and completed screening tympanometry at each test
      session. The infants detected a 4000 Hz tone at levels ranging from 25 to 50 dB
      SPL; psychometric functions and thresholds for the tone were obtained. RESULTS:
      Infants with Down syndrome completed 80% of the test sessions they began, a rate
      similar to that seen in normally developing infants in the same type of study.
      Performance improved with increasing stimulus level, as one would expect, and
      thresholds were obtained from 15 of 16 infants for at least one age. The
      performance of infants with Down syndrome generally improved with age. The
      sensitivity of 2- to 3-mo-olds was poorer than that of older infants, but little
      if any improvement in sensitivity occurred between 4 and 12 mo. This pattern is
      similar to that seen in normally developing infants. Thresholds of infants with
      Down syndrome were 10 to 25 dB higher than those reported for normally developing
      infants. The psychometric functions of infants with Down syndrome were shallower
      than the psychometric functions of normally developing infants, and the slope of
      the psychometric functions did not change with age. Infants with Down syndrome
      achieved only 75 to 80% correct at any of the levels tested, 5 to 10% poorer than
      reported for other infants. These characteristics of the psychometric functions
      of the infants with Down syndrome suggest that they are inattentive during
      testing more often than are normally developing infants. CONCLUSIONS: An observer
      based procedure can be used to obtain reasonable thresholds from infants with
      Down syndrome who are as young as 2 mo of age. Both sensory and nonsensory
      factors could contribute to the threshold elevation seen in infants with Down
      syndrome. At least on preliminary examination, the course of auditory sensitivity
      development of infants with Down syndrome is qualitatively similar to that seen
      in normally developing infants.

PMID- 8979035
TI  - The hearing threshold levels of children at school age.
AB  - OBJECTIVE: To measure the hearing threshold levels by air conduction in a group
      of unselected and a group of selected (otologically normal) school-aged children.
      DESIGN: Six hundred eighty-seven unselected school children representing three
      age groups and 471 selected, otologically normal children were examined by pure
      tone audiometry. RESULTS: The obtained results showed that hearing levels
      improved with age from 7 to 10 yr in children in both groups. The pure-tone
      averages (PTAs) of the right and the left ear in otologically normal children
      were, respectively, 1.8 and 1.2 dB HL in 7-yr-old children, -0.9 and -1.7 dB HL
      in 10-yr-old children, and -1.3 and -2.0 dB HL in 14-yr-old children. The PTAs
      were 0.2 to 1.9 dB poorer in the groups of unselected children. CONCLUSIONS: The
      present study provides new data on the hearing sensitivity among unselected 7-,
      10-, and 14-yr-old school children. Furthermore, it provides normative values on
      the hearing thresholds of otologically normal children in these three age groups.

PMID- 8979036
TI  - Word recognition in continuous and interrupted broadband noise by young normal
      hearing, older normal-hearing, and presbyacusic listeners.
AB  - OBJECTIVE: Word recognition performance in continuous and interrupted broadband
      noise was examined in young normal-hearing (YNH), older normal-hearing (ONH), and
      presbyacusic (older hearing-impaired [OHI]) listeners. DESIGN: Participants (N =
      36) were presented with identical Northwestern University Auditory Test No. 6
      stimuli at 30 dB sensation level re their respective speech reception thresholds.
      The speech stimuli were presented in quiet and in both competing noise conditions
      with signal to noise ratios (S/Ns) of 10, 5, 0, -5, -10, -15, and -20 dB.
      RESULTS: In general performance was superior in quiet, improved with increasing
      S/N, and was greater in the interrupted broadband noise than in the continuous
      broadband noise. Significant main effects of group and S/N were found in both
      competing noises (p < 0.0001). Post hoc pairwise comparisons revealed all groups
      performed differently, with superior performance being displayed by the YNH group
      followed by the ONH and OHI groups, respectively (p < 0.05). A significant group
      by S/N interaction was observed in only the interrupted noise condition (p =
      0.019). The degree of change in word recognition performance as a function of S/N
      was greatest in the OHI group followed by the ONH group and the YNH group.
      CONCLUSIONS: Group effects observed in the interrupted noise would imply that the
      two older groups of listeners had an auditory temporal deficit relative to the
      YNH listeners. The paradigm reveals the patency of the temporal processes that
      are responsible for the perceptual advantage (i.e., a release from masking) a
      listener has in interrupted competing stimulus.

PMID- 8979037
TI  - Comparison of conventional amplification and an assistive listening device in
      elderly persons.
AB  - OBJECTIVE: To assess the impact of personal amplification systems on quality of
      life of elderly persons and to compare conventional hearing aid with assistive
      listening device. DESIGN: Audiologic, neuropsychologic, and quality-of-life
      measures were prospectively administered to 180 elderly, hearing-impaired persons
      before and after randomized 6 wk trials of four treatment conditions-a no
      amplification condition and three different types of amplification: 1)
      conventional hearing aid, 2) assistive listening device, and 3) a combination of
      the two systems. All subjects volunteered to participate in a study comparing
      different amplification systems and were paid for their participation. RESULTS:
      Both self-perceived handicap and speech understanding were improved significantly
      by all three amplification systems. There were no significant group differences
      between new users and previous users of amplification in self-assessed handicap
      after amplification use. Anecdotally, subjects preferred the sound quality of the
      assistive listening device, but an overwhelming majority (97.3%) still chose the
      conventional aid for use in daily living. CONCLUSIONS: Results affirm the
      significant impact of amplification on the quality of life of elderly persons.
      The strong preference for the conventional hearing aid in everyday use
      undoubtedly reflects the fact that elderly users usually are not willing to
      endure the difficulties associated with the use of remote-microphone systems.

PMID- 8979038
TI  - Refinement and psychometric evaluation of the Attitudes Toward Loss of Hearing
      Questionnaire.
AB  - OBJECTIVE: To refine and statistically validate the Attitudes Toward Loss of
      Hearing Questionnaire (ALHQ) so that it will be appropriate for clinical
      application and to understand some of the personality attributes underlying
      attitudes toward hearing loss. DESIGN: An American-English version of an ALHQ,
      originally designed by Brooks (1989), was completed by 226 men; a subset of 80
      also completed personality questionnaires. All subjects underwent pure-tone
      testing and speech audiometry. Factor analysis was used to extract scales from
      the ALHQ. Reliability analyses using Cronbach's alpha were carried out on each
      scale. Test-retest reliability was evaluated from questionnaires completed 6 to
      18 mo after initial administration. Multiple regression analysis was used to
      examine the audiometric and personality determinants of attitudes. RESULTS: Five
      reliable scales were extracted from a 24-question version of the ALHQ: 1) Social
      and Emotional Impact of Hearing Loss, 2) Acceptance/ Adjustment to Hearing Loss,
      3) Perceived Support from Significant Others, 4) Hearing Aid Stigma, and 5)
      Awareness of Hearing Loss. Audiometric data explained little of the variance in
      attitude scores; age and other demographic factors did not correlate with
      attitudes either. The personality traits of extroversion, self-esteem, and
      anxiety/neuroticism played a larger role in determining attitude. CONCLUSIONS:
      The ALHQ is psychometrically acceptable and is a potentially useful clinical
      tool. It is quick and easy to complete and to score and could be used as a basis
      for counseling and for following attitude change in patients over time.

PMID- 8979039
TI  - Measures of hearing aid gain for real speech.
AB  - OBJECTIVE: Non-speech stimuli typically are used to estimate the electroacoustic
      characteristics of a hearing aid. At present, there is no consensus as to what
      type of input stimulus will best represent the gain for real speech. The purpose
      of this study was to measure hearing aid gain using continuous discourse and to
      compare these values with gain measured with five different types of simpler
      stimuli. DESIGN: Hearing aid gain as a function of frequency was measured in a 2
      cm3 coupler for 20 commercially available hearing aids. Circuitry included
      features such as linear peak clipping, compression limiting, 1-, 2-, and 3
      channel full dynamic range compression, and adaptive compression. Input stimuli
      were a) 15 sec of continuous discourse, b) swept pure tones (SPTs), c) speech
      weighted composite noise (SWCN), d) simulated speech, e) speech weighted warble
      tones, and f) speech modulated noise. Input levels ranged from 50 to 80 dB SPL.
      RESULTS: In general, both SPTs and SWCN tended to underestimate the high
      frequency gain for real speech. These discrepancies increased as a function of
      input intensity. On average, the SPT produced the greatest departure from the
      gain for real speech, producing differences for individual hearing aids as large
      as 10 to 14 dB. An analysis by circuit type revealed that discrepancies most
      likely occurred when a hearing aid was operating in a nonlinear mode. Of the five
      non-speech stimuli used, speech modulated noise and simulated speech seemed to
      provide the closest approximation to the gain measured with continuous discourse.
      CONCLUSIONS: When a hearing aid is operating in a nonlinear mode, non-speech
      stimuli will tend to underestimate the gain for real speech, particularly in the
      high frequencies. Under some conditions, these discrepancies may impact clinical
      decisions during the hearing aid fitting process. Additional studies are needed
      to elucidate the factors that contribute to the gain discrepancies observed in
      this study and to explore the use of additional stimuli (including short speech
      samples), which may result in better predictions of the gain for speech.

PMID- 8979040
TI  - Initial independent results with the Clarion cochlear implant.
AB  - OBJECTIVE: This paper reports some preliminary findings from patients, implanted
      at the University of Iowa, using the Advanced Bionics Clarion cochlear implant
      (version 1.0). We compared the performance of patients using both simultaneous
      analog and nonsimultaneous pulsatile processing strategies. The performance of
      Clarion patients was also compared with a group of patients who were using either
      the feature-extraction Nucleus cochlear implant or the compressed-analog Ineraid
      cochlear implant. DESIGN: One aim was to compare the analog and pulsatile
      stimulation in 19 patients using the Clarion implant. This aim could be
      accomplished only partially because of difficulties encountered in adequately
      fitting patients with the analog strategy. A second aim was to compare the
      Clarion users' performance with feature-extraction Nucleus and compressed-analog
      Ineraid patients. Comparisons were made with all patients having 9 mo experience
      postimplantation. RESULTS: Subjects performed better using the pulsatile mode
      compared with the analog mode. All subjects chose to use the pulsatile strategy
      after the first 3 mo of the study. Results comparing performance at 9 mo with our
      compressed-analog Ineraid and feature-extraction Nucleus patients indicated, in
      general, better average performance for the Clarion users. CONCLUSIONS: We
      conclude that the pulsatile version of the Clarion cochlear implant typically
      produces superior performance to the analog version of that device at this stage
      in its development. After 9 mo of experience, users of the Clarion implant are
      performing better than are users of the feature-extraction Nucleus and compressed
      analog Ineraid cochlear implants with comparable amounts of experience.

PMID- 8979041
TI  - Electric response audiometry in young children before cochlear implantation: a
      short latency component.
AB  - OBJECTIVE: Evaluation of a short latency component (SLC) observed in profoundly
      deaf young children during recordings of the auditory brain stem response (ABR)
      before cochlear implantation. DESIGN: Seventy young children (ages 2 to 11 yr)
      were investigated as part of their routine audiologic and diagnostic assessment,
      before cochlear implantation. The ABR was evoked using click stimuli and tone
      pips (500 Hz and 1 kHz) at intensity levels up to 105 dB nHL. The incidence of
      the SLC arising at a latency of 3 msec with high level click stimuli, in addition
      to residual ABR waves, was assessed. RESULTS: An SLC was observed in a total of
      18 of the 70 children investigated. It was present in 15 out of 31 congenitally
      deaf children (48%) compared with only 2 out of 33 children deafened after
      meningitis (6%). A chi-squared test employing a 2 x 2 contingency table shows
      that this dependency on etiology of deafness is highly statistically significant
      (p < 0.001). The presence of the SLC in the congenitally deaf children is related
      to age at the time of the Electric Response Audiometry test and is more likely to
      be observed in the younger child (p < 0.01). CONCLUSIONS: Interpretation of the
      ABR in profoundly deaf children should take into consideration the possible
      presence of the SLC. An evoked potential arising from stimulation of the
      vestibular system, particularly the vestibular nuclei, is proposed as a likely
      origin for this component. Damage to sensory cells in the vestibular portion of
      the labyrinth might explain why an SLC is seen rarely in cases of deafness after
      meningitis.

PMID- 8979042
TI  - Auditory evoked brain stem responses to trains of stimuli in human adults.
AB  - OBJECTIVE: This study describes the effect of train length, interstimulus
      interval, intertrain interval (ITI), and stimulus duration on the transition from
      the unadapted to the adapted wave V auditory evoked brain stem response (ABR).
      DESIGN: ABRs were recorded to stimuli presented at two different rates: a slow
      rate characterizing the unadapted response and a fast rate characterizing the
      adapted response. Trains of stimuli (a sequence of stimuli separated by intervals
      of silence) also were presented. Different stimulus parameters defining the
      trains were varied. RESULTS: Given a sufficiently long ITI, the latency
      prolongation to the first three or four stimuli in a train was rapid. It was
      similar for trains differing in number of stimuli. After the first three or four
      stimuli, there was a more gradual latency prolongation as a function of stimulus
      number. Shorter ITIs had the effect of prolonging the latencies to all the
      stimuli in the trains, reducing the rate of latency prolongation over the first
      few stimuli, and causing responses to trains of different length to differ (e.g.,
      two click train responses were shorter latency than four click train responses).
      An unexpected result was the latency prolongation of wave Vs after the
      presentation of the stimulus trains. CONCLUSIONS: In response to a train of
      clicks, there seems to be a rapid increase in wave V latency to the first few
      clicks in the train followed by a more gradual latency prolongation to subsequent
      clicks in the train.

PMID- 8979043
TI  - Blockade of opioid-induced changes in auditory function at the level of the
      cochlea.
AB  - OBJECTIVE: We have previously investigated the auditory neural effects of the
      kappa-opioid receptor agonist, (-)pentazocine. When administered intravenously
      (i.v.), this drug temporarily alters auditory nerve compound action potential
      (CAP) amplitudes. To test the hypothesis that the observed neural effects of i.v.
      (-)pentazocine occur via kappa-receptor interactions within the cochlea, we
      attempted to block these effects by employing a specific kappa-opioid receptor
      antagonist applied directly to the cochlear round window (RW) membrane. DESIGN:
      In 31 normal-hearing, male pigmented chinchillas, amplitude changes in the click
      evoked auditory CAP (N1) were tracked at six stimulus intensities during a
      baseline and a postbaseline period in which i.v. (-)pentazocine (8 mg/kg) was
      administered. (-)Pentazocine administration was preceded by the delivery to the
      cochlear RW membrane of an artificial perilymph solution given alone or
      containing the kappa-opioid receptor selective antagonist, norbinaltorphimine
      (Nor-BNI), which was administered at two concentrations in separate groups of
      animals. RESULTS: The amplitude increase in the CAP after (-)pentazocine was
      significantly reduced when i.v. (-)pentazocine was preceded by RW-administered
      Nor-BNI (4 mM). CONCLUSIONS: The reversibility of agonist effects by Nor-BNI
      indicates direct or indirect opioid kappa-receptor-mediated auditory neural
      effects at the level of the cochlea and suggests a connection between kappa
      receptors and auditory neural function.

PMID- 8979044
TI  - Effects of stapedial arch fractures on conductive hearing loss and stapedial
      reflexes.
AB  - OBJECTIVE: It has been stated in the clinical literature that stapedial fractures
      could produce a significant conductive hearing loss while leaving the
      contralateral stapedial reflex intact. The objective of this study is to test
      this hypothesis in an animal model. DESIGN: Nine hooded rats underwent acoustic
      stapedial reflex (ASR) and cochlear microphonic (CM) threshold determinations
      before and after middle ear surgery. An argon laser was used to divide the tensor
      tympani tendon, the anterior stapedial curs, and the posterior stapedial crus,
      sequentially. The initial functional measures were repeated after each laser
      procedure to document its effect. RESULTS: Dividing the tensor tympani tendon and
      the anterior stapedial crus had variable and small effects on ASR and CM
      thresholds. Division of the second (posterior) crus eliminated stapedial reflexes
      and produced a significant hearing loss. CONCLUSIONS: This study refutes the
      hypothesis that fracture of one (anterior) stapedial crus will significantly
      alter ossicular sound transmission, but it supports the hypothesis that measured
      stapedial reflexes would not be significantly altered by a single crus fracture.
      Therefore, the surgeon exploring an ear for a conductive hearing loss with an
      intact contralateral stapedial reflex should look carefully for another source of
      the hearing loss if finding only a single stapedial arch fracture.

PMID- 8979045
TI  - Two different patterns of airway branching regulated by different components of
      the extracellular matrix in vitro.
AB  - This study examined the effects of beta-D-xyloside (an inhibitor of proteoglycan
      synthesis) and cis-4-hydroxyl-L-proline (an inhibitor of collagen synthesis) on
      branching morphogenesis in cultures of fetal rat lung. Lungs from day 15
      gestation were incubated for 4 days in (1) the control medium (Dulbecco's
      Modified Eagle Medium + 10% Fetal Bovine Serum) alone (control), (2) control
      medium plus 2 mM beta-D-xyloside (beta-XYL), (3) control medium plus 2 mM alpha-D
      xyloside (alpha-XYL), (4) control medium plus 50 micrograms/mL cis-4-hydroxy-L
      proline (cis-HYP). The number of peripheral buds of left lungs was counted daily.
      Histological examination was performed on lungs on days 2 and 4. beta-XYL
      inhibited proximal monopodial branching on day 2 without affecting lung size, but
      produced numerous peripheral buds on day 4 which were of abnormal appearance,
      suggesting that lung airway branching and growth may be regulated by different
      mechanisms. Histology and morphometry showed significantly enlarged airspaces and
      diminished mesenchyme. cis-HYP did not affect proximal branching on 2 days in
      culture, but inhibited further dichotomous branching and lung growth after 2
      days. On day 4, diminished branching and lung growth was accompanied by a
      proportional decrease in mesenchyme. The difference between effects of beta-XYL
      and cis-HYP on the branching pattern suggests that proteoglycans and collagen are
      involved in different patterns of branching morphogenesis.

PMID- 8979046
TI  - Specific neutrophil elastase inhibitor does not attenuate acute lung injury
      induced by air embolism in awake sheep.
AB  - To investigate the role played by neutrophil-derived elastase in acute lung
      injury, this study examined the effects of treatment of ONO-5046, a competitive,
      reversible, and specific neutrophil elastase inhibitor, on lung dysfunction
      induced by air emboli in awake sheep. Sheep were prepared with chronic lung lymph
      fistula. In experiment 1, air (1.23 mL/min) was infused over a 2-h period into
      the pulmonary artery and hemodynamic monitoring was performed over a 5-h period.
      In experiment 2, air was infused in the same manner as in experiment 1, 1 h after
      the continuous infusion of ONO-5046 (10 mg/kg h-1) had begun. In experiment 1,
      pulmonary artery pressure (Ppa) increased from the baseline value of 17.0 +/- 0.7
      cm H2O to 28.3 +/- 1.8 1 h after the beginning of the air infusion. Ppa returned
      to the baseline values within 1 h after the air infusion was stopped. Lung lymph
      flow (Qlym) increased from the baseline value of 3.7 +/- 0.7 mL/0.5 h to 8.5 +/-
      1.9 after 1 h of air infusion. After the air infusion was stopped, Qlym continued
      to increase. When sheep were treated with ONO-5046, Ppa and Qlym increased in a
      fashion similar to that in the experiment 1. These findings suggest that ONO-5046
      does not attenuate air embolism-induced lung injury and that neutrophil-derived
      elastase may not play an important role in air embolism-induced lung injury in
      awake sheep.

PMID- 8979047
TI  - Expression of CYP2B1 in freshly isolated and proliferating cultures of epithelial
      rat lung cells.
AB  - Bronchiolar Clara cells and alveolar type 2 cells of the lung are known to
      express relatively high levels of P450 enzymes compared to other pulmonary cells.
      Populations of enriched type 2 cells and Clara cells were isolated from rat lung
      by a procedure including lung perfusion, protease digestion, centrifugal
      elutriation, and differential attachment. Alveolar macrophages were removed by
      lavage. The purity of the type 2 cell-enriched population was approximately 90%,
      and the purity of the Clara cell-enriched population was 40-50%. Both type 2
      cells and the cells of the Clara cell-enriched population proliferated in
      culture. CYP2B1 mRNA was expressed approximately to the same level in type 2
      cells and the Clara cell-enriched population. The mRNA levels remained roughly
      constant for both cell types throughout the culture period, except for an early
      transient reduction. The apoenzyme level of CYP2B1 was 2-3 times higher in
      freshly isolated cells of the Clara cell-enriched population than in the type 2
      cells. Both epithelial cell types showed decreased level of CYP2B1 apoenzyme in
      culture. The differences in the CYP2B1 mRNA and apoenzyme expression levels in
      freshly isolated cells and cultured cells suggest the existence of a post
      transcriptional regulatory mechanism for CYP2B1 expression in lung cells. The
      characterization of specific functions of lung cells in culture, such as P450
      gene expression, provides necessary information for the use of the cells in in
      vitro pulmonary toxicology.

PMID- 8979048
TI  - Pulmonary response to plasmid DNA and immunohistochemical localization of
      transgene expression.
AB  - Tracheal insufflation of chloramphenicol acetyltransferase (CAT) expression
      plasmid (pBL-CAT) DNA without any gene delivery system results in transfection of
      rat lungs (Am J Physiol. 1995;268:L1052-L1056). This study investigated the
      pulmonary response to tracheal insufflation of plasmid DNA and the
      immunohistochemical localization of transgene expression in the lungs.
      Insufflation of 300 micrograms pBL-CAT DNA resulted in lung transfection without
      causing pulmonary injury as judged from the protein content of alveolar lavage
      fluid, pleural effusion, and lung ultrastructure. There was, however, an acute
      alveolar inflammatory response at 6 h after insufflation due to contaminating
      endotoxin present in the plasmid DNA preparation. Reducing the amount of
      endotoxin from 0.022 to 0.0015 microgram per 300 micrograms pBL-CAT completely
      abolished the acute alveolar inflammatory response without affecting the lung
      transfecting efficiency of pBL-CAT. Immunohistochemistry revealed that
      insufflation of pBL-CAT transfected predominantly small airway epithelial cells.

PMID- 8979049
TI  - Circulatory changes after surfactant bolus instillation in lung-lavaged adult
      rabbits.
AB  - Following surfactant instillation in infants treated for respiratory distress
      syndrome, a mean arterial blood pressure (MABP) decrease is often observed. Its
      etiology and pathogenesis are still unknown. In this study various circulatory
      parameters were recorded continuously after surfactant instillation to elucidate
      the role of pulmonary vascular resistance as one possible cause for the MABP
      drop. Seven anesthetized adult New Zealand white rabbits were artificially
      ventilated after tracheotomy. Arterial and right atrial pressure were recorded
      continuously. Pulmonary artery pressure and cardiac output were determined by
      means of a thermodilution catheter. After inducing surfactant deficiency by
      repeated saline lavages, 200 mg/kg body weight of a natural surfactant
      preparation was administered by tracheal bolus instillation. PaO2 increased
      rapidly from 8.0 +/- 1.3 kPa to 51.2 +/- 8.8 kPa (mean +/- standard deviation)
      within 2 min (p < .05). MABP dropped from 12.1 +/- 1.9 kPa to 8.9 +/- 2.3 kPa
      within 2 min (p < .05). Pulmonary artery pressure, cardiac output, and right
      atrial pressure did not change during the observation period of 60 min. The
      results suggest that a peripheral vasodilatation is the most likely cause for the
      drop in MABP.

PMID- 8979050
TI  - Comparison of lymphocyte subsets, monocytes, and NK cells in three different lung
      compartments and peripheral blood in the rat.
AB  - Investigations on leukocyte populations in the lung have shown that lymphocytes
      are found in different anatomical compartments. Lymphocytes can be seen to a
      different extent in the lung interstitium, the epithelium and lamina propria of
      the bronchi, the bronchoalveolar space, and the marginal lung vascular bed.
      Previous studies focused on one compartment only, or a mixture of leukocytes from
      lung homogenates were prepared. This study compared cellular yields from the lung
      parenchyma, the bronchoalveolar space, and the perfusate of the lung vasculature
      of healthy male Lewis rats. All compartments were investigated in the same
      animal, and seven different lymphocyte subsets, monocytes, and natural killer
      (NK) cells were analyzed using flow cytometry. It was found that the perfusate
      contained a high proportion of CD4+ lymphocytes compared to the lung
      interstitium. A very high proportion of CD4+ lymphocytes in the bronchoalveolar
      lavage (BAL) expressed markers for "memory" T cells. Compared to the blood, the
      percentage of B and T cells was much lower in the perfusate, whereas the NK cells
      and monocytes were more frequent. Analysis of leukocyte subsets within all
      compartments revealed specific, distinguishable cell compositions. Extraction of
      interstitial lung cells was performed using two different methods. Enzymatic
      digestion of the lung tissue was compared with a mechanical disruption method.
      Hardly any differences were observed between the two methods regarding the
      distribution of lymphocyte subsets, monocytes, and NK cells. These data document
      the need to study more than one compartment before extrapolating to lymphocytes
      in the lung in general. Furthermore, changes in numbers of leukocytes and subsets
      can now be studied in models of lung infections and immune reactions, including
      the entry from the blood and intrapulmonary migration from one lung compartment
      to the other.

PMID- 8979051
TI  - Long-term follow-up after endoscopic sphincterotomy for bile duct stones in
      patients younger than 60 years of age.
AB  - BACKGROUND: Little is known about the long-term effects of endoscopic biliary
      sphincterotomy. METHODS: We retrospectively evaluated the rate of late
      complications after endoscopic sphincterotomy (EST) for bile duct stones.
      Patients had to meet the following inclusion criteria: (1) treated between 1976
      and 1980, (2) complete stone removal after EST, (3) prior cholecystectomy or
      elective cholecystectomy within 2 months after EST, and (4) 60 years old or
      younger at the time of ERCP. A total of 100 patients were identified. Information
      was obtained from general practitioners and patients by telephone. Patients
      completed a postal questionnaire and a blood sample was obtained for liver
      function tests. RESULTS: Information was obtained for 94 patients (in the
      majority of cases [87%] from multiple sources). There were 26 men and 68 women
      with a mean age of 51 years at the time of ERCP (range, 23 to 60 years). Early
      complications (< 30 days) occurred in 14 patients (15%). One patient died of a
      retroperitoneal perforation secondary to EST. During a median period of 15 years
      (range, 3 to 18 years), 22 patients (24%) developed a total of 36 late
      complications. There were 21 patients with symptoms of recurrent bile duct stones
      and one patient with biliary pancreatitis. Other late complications, such as
      recurrent ascending cholangitis or malignant degeneration, were not observed. An
      ERCP was performed in 20 of the 22 patients with late complications and
      demonstrated bile duct stones in 13, combined with stenosis of the EST opening in
      9 patients. Late complications were initially managed endoscopically and/or
      conservatively. One patient underwent surgery after failed endoscopic treatment
      and one patient died of cholangitis before she could undergo an ERCP. Twelve
      other patients died of unrelated causes during follow-up. CONCLUSIONS: After EST
      for bile duct stones, late complications occur in a significant proportion of
      patients. Stone recurrence remains the most important problem, but can in general
      be managed endoscopically.

PMID- 8979052
TI  - The acute and long-term effect of balloon sphincteroplasty on papillary structure
      in pigs.
AB  - BACKGROUND: Balloon dilation or sphincteroplasty is emerging as a potentially
      safe and effective alternative to sphincterotomy in the management of bile duct
      stones. However, concerns related to the possible development of fibrosis or
      papillary stenosis led us to investigate the acute and long-term effects of
      balloon sphincteroplasty on papillary structure. METHODS: Sixteen pigs (45 to 50
      kg) underwent transduodenal cannulation of the bile duct while under general
      anesthesia. Balloon sphincteroplasty was performed in 10 pigs to a diameter of 8
      mm at a pressure of 10 atm. Sphincterotomy was carried out in 3 pigs while 2
      other untreated pigs acted as controls. Eleven animals were sacrificed at
      intervals from 15 to 120 minutes after balloon sphincteroplasty or
      sphincterotomy. The remaining 5 animals were sacrificed between 6 and 12 weeks
      later. Histologic sections through the papilla were assessed for evidence of
      morphologic changes. RESULTS: When compared with controls, sections taken 15 to
      120 minutes after balloon sphincteroplasty showed a progressive increase in acute
      inflammation extending transmurally. Intramucosal, but no transmural, hemorrhage
      was noted. No architectural distortion or smooth muscle disruption was observed
      in contrast to the transmural hemorrhage, smooth muscle disruption, and mucosal
      necrosis seen following sphincterotomy. After 6 to 12 weeks, mild chronic
      inflammation with follicular hyperplasia was present but no smooth muscle
      disruption or fibrosis was observed. CONCLUSION: Balloon sphincteroplasty causes
      an acute transmural inflammatory response and chronic follicular hyperplasia but
      is not associated with fibrosis or altered papillary architecture.

PMID- 8979053
TI  - Endosonography-guided celiac plexus neurolysis.
AB  - BACKGROUND: We have evaluated the safety and efficacy of performing
      endosonography-guided celiac plexus neurolysis (EUS CPN) in patients with pain
      due to intra-abdominal malignancies. METHODS: Thirty patients with upper
      abdominal pain requiring narcotic analgesia and suspected or known intra
      abdominal malignancy were selected for EUS CPN. This group included 25 patients
      with pancreas carcinoma and 5 patients with intra-abdominal metastases. Using the
      linear array ultrasound endoscope and a prototype needle catheter, transgastric
      injection of the celiac plexus with bupivacaine and 98% dehydrated absolute
      alcohol was accomplished. RESULTS: Pain scores were significantly lower compared
      with baseline at 2, 4, 8, and 12 weeks after EUS CPN (median follow-up: 10
      weeks). At these follow-up intervals, 82% to 91% of patients required the same or
      less pain medication and 79% to 88% of patients had persistent improvement in
      their pain score. Comparison of patients with TXNXM1 versus TXNXMO pancreatic
      carcinoma revealed higher initial pain scores (7.9 +/- 1.92 versus 5.8 +/- 2.0, p
      = .02) and a greater decline in pain scores (decrease of 6.1 +/- 3.1 versus 4.8
      +/- 2.0, p = .004). Complications were minor and consisted of transient diarrhea
      in four patients. CONCLUSION: EUS CPN is a safe and effective means for improving
      pain control in patients with intra-abdominal malignancy. The technique may be
      performed as an outpatient at the same setting as the EUS staging examination.

PMID- 8979054
TI  - Results of culture form colonoscopically obtained specimens for bacteria and
      fungi in HIV-infected patients with diarrhea.
AB  - BACKGROUND: The aim of our study was to determine the diagnostic yield of culture
      for bacteria and fungi from colonic biopsy specimens in 290 consecutive HIV
      infected patients with diarrhea. METHODS: During each colonoscopy, three biopsy
      specimens were homogenized and cultured on media for Salmonella and Shigella and
      for Campylobacter and Yersinia, on Loewenstein medium and on Sabouraud medium.
      RESULTS: Cultures were found positive for one (n = 32) or two (n = 5) infectious
      agents in 37 cases, i.e., in 12.8% of the patients. Bacteria were isolated in 24
      cases, and identified as Campylobacter jejunl-coli (n = 14), Salmonella (n = 2),
      Shigella (n = 1), or Pseudomonas aeruginosa (n = 7). Among the 14 patients with
      C. jejuni-coli intestinal infection, 11 had normal-appearing mucosa at
      colonoscopy, and 3 had a concomitant stool culture negative for Campylobacter.
      Mycobacterial cultures were positive for Mycobacterium avium intracellulare in 6
      patients, who were already known as having a disseminated M. avium intracellulare
      infection from positive blood cultures. Fungal cultures were positive for Candida
      in 10 cases, without clear clinical significance. CONCLUSIONS: The overall yield
      of culture for bacterial pathogens from colonic tissue in HIV-infected patients
      with diarrhea is low, but some individual cases of C. jejuni-coli infections may
      be detected from colonic tissue culture and not diagnosed by concomitant stool
      culture.

PMID- 8979055
TI  - Cutting thread at flexible endoscopy.
AB  - BACKGROUND: New thread-cutting techniques were developed for use at flexible
      endoscopy. A guillotine was designed to follow and cut thread at the endoscope
      tip. A new method was developed for guiding suture cutters. Efficacy of Nd: YAG
      laser cutting of threads was studied. Experimental and clinical experience with
      thread-cutting methods is presented. METHODS: A 2.4 mm diameter flexible thread
      cutting guillotine was constructed featuring two lateral holes with sharp edges
      through which sutures to be cut are passed. Standard suture cutters were guided
      by backloading thread through the cutters extracorporeally. A snare cutter was
      constructed to retrieve objects sewn to tissue. Efficacy and speed of Nd: YAG
      laser in cutting twelve different threads were studied. RESULTS: The guillotine
      cut thread faster (p < 0.05) than standard suture cutters. Backloading thread
      shortened time taken to cut thread (p < 0.001) compared with free-hand cutting.
      Nd: YAG laser was ineffective in cutting uncolored threads and slower than
      mechanical cutters. Results of thread cutting in clinical studies using sewing
      machine (n = 77 cutting episodes in 21 patients), in-vivo experiments (n = 156),
      and postsurgical cases (n = 15 over 15 years) are presented. CONCLUSIONS: New
      thread-cutting methods are described and their efficacy demonstrated in
      experimental and clinical studies.

PMID- 8979056
TI  - Use of a pediatric colonoscope improves the success of total colonoscopy in
      selected adult patients.
AB  - BACKGROUND: Colonoscopy using a standard adult colonoscope can be difficult or
      impossible when there is a fixed, angulated sigmoid colon or stricture. It is
      sometimes possible to traverse such segments using a smaller-diameter, more
      flexible pediatric colonoscope. METHODS: For this prospective study, one
      endoscopist started 645 consecutive, elective colonoscopies with a standard adult
      Olympus CF-100L colonoscope (52% women, 48% men). There were 36 examinations
      (5.6%) in which the adult colonoscope could not be passed through a fixed,
      angulated sigmoid colon (n = 34) or a sigmoid colonic stricture (n = 2). In such
      instances (33 women and 3 men), the endoscopist switched to a pediatric
      colonoscope. RESULTS: The pediatric colonoscope successfully reached the cecum in
      21 of the 36 cases (58.3%). The figure was 38.5% for the older Olympus CF-P20L
      fiberoptic colonoscope (n = 13) and 69.6% for the newer Olympus PCF-100
      videocolonoscope (n = 23). Concomitant conditions in the 34 patients in whom the
      pediatric colonoscope was used because of a fixed, angulated sigmoid included
      previous pelvic surgery in 22, pelvic radiation therapy in 2, pelvic
      endometriosis in 3, and two with previous sigmoid diverticulitis. CONCLUSIONS:
      The pediatric colonoscope, and particularly the newer Olympus PCF-100
      colonoscope, is very useful in adult patients in whom it is not possible to
      traverse a fixed, angulated sigmoid colon or stricture using the standard adult
      colonoscope. This is predominantly a problem of female patients. Previous pelvic
      surgery may be an important causative factor in this regard.

PMID- 8979057
TI  - Quantitative noninvasive testing for Helicobacter pylori does not predict
      gastroduodenal ulcer disease.
AB  - BACKGROUND: Helicobacter pylori is strongly associated with gastric and duodenal
      ulcer disease. However, the diagnosis of gastroduodenal ulcers requires an
      endoscopic or radiographic examination. In this study, we attempted to establish
      a relationship between the magnitude of [13C]urea breath test results or serum H.
      pylori IgG levels and endoscopic findings in H. pylori-infected individuals.
      METHODS: Patients who had undergone endoscopy and had a positive [13C]urea breath
      test and/or positive H. pylori IgG serology were identified. Endoscopic diagnoses
      included duodenal ulcer, gastric ulcer, nonulcer dyspepsia, and others. Results
      of 6% or greater on the [13C]urea breath test was defined as positive for H.
      pylori infection. H. pylori IgG serology was determined by an enzyme linked
      immunosorbent assay with values of greater than or equal to 1.0 being
      seropositive. RESULTS: One hundred seventy-five patients were seropositive (mean
      = 3.01 +/- 1.58). One hundred sixty-eight patients had a positive [13C]urea
      breath test (mean = 25.43 +/- 16.90). One hundred fifty-five patients were common
      to both the groups. Statistical analysis did not reveal any relationship between
      quantitative [13C]urea breath test results or H. pylori IgG values and endoscopic
      diagnoses. CONCLUSION: The magnitude of [13C]urea breath test or H. pylori IgG
      serology cannot be used to predict the presence or absence of gastroduodenal
      ulcer disease.

PMID- 8979059
TI  - Papillary roof incision using the Erlangen-type pre-cut papillotome to achieve
      selective bile duct cannulation.
AB  - BACKGROUND: Prior studies evaluating pre-cutting the major papilla to access the
      bile duct when standard cannulation falls have usually used the needle-knife
      papillotome. We conducted a prospective study to evaluate the efficacy and safety
      of an Erlangen-type pre-cut papillotome for pre-cutting. PATIENTS AND METHODS:
      Three hundred twenty-seven patients (114 men, mean age 67 years) who underwent
      first-time sphincterotomy at our institution were included. Pre-cutting was
      performed if free and wire-guided cannulation of the bile duct failed according
      to an algorithm. RESULTS: Pre-cutting was performed in 123 patients (38%) and
      selective cannulation was successful in all. Post-ERCP serum pancreatic enzyme
      levels were more frequently elevated in the pre-cut group (50%) than the non-pre
      cut group (27%, p < 0.001); however, there was no difference in the incidence of
      post-ERCP pancreatitis (pre-cut = 2.7%, 95% CI: 0.66% to 7.6%; non-pre-cut =
      1.6%, 95% CI: 0.3% to 4.7%). The incidence of bleeding was similar (pre-cut,
      2.4%, non-pre-cut, 3.9%; p > 0.05). CONCLUSION: Pre-cutting the major papilla for
      biliary access using the Erlangen-type pre-cut papillotome is an effective and
      reasonably safe procedure when performed by endoscopists with extensive
      experience in pancreatobiliary endoscopy.

PMID- 8979058
TI  - Bacterial density of Helicobacter pylori predicts the success of triple therapy
      in bleeding duodenal ulcer.
AB  - BACKGROUND: We studied whether different initial bacterial densities of
      Helicobacter pylori would alter the eradication rate of H. pylori by triple
      therapy (amoxicillin 500 mg t.i.d. and metronidazole 500 mg t.i.d. for 14 days;
      bismuth subcitrate 120 mg t.i.d. for 28 days) in patients with duodenal ulcer
      bleeding. METHOD: One hundred thirty-six cases with duodenal ulcer bleeding and
      H. pylori infection (proved by rapid urease test and histology during emergency
      endoscopy) were studied. One hundred twenty-seven of these patients completed a
      course of triple therapy. In each case, anti-H. pylori IgG titer, gastric
      biopsies for H. pylori density (score 1 to 5), and evaluation of severity of
      gastritis were collected at the first endoscopy and 1 month after completion of
      the triple therapy. RESULTS: The ulcer healing rate was 84.3% (107 of 127) at the
      time of the second evaluation. The eradication rate of H. pylori was 76.4% (97 or
      127). Eradication for H. pylori failed in 30 cases. In these eradication failure
      cases, initial serologic titer and density of H. pylori were higher than those of
      eradication success cases. The eradication rate of H. pylori decreased as the
      initial density of H. pylori increased (density of H. pylori: 1, 88.3%; 2, 83.8%;
      3, 74.2%; 4, 68%; 5, 50%). At the second evaluation, the serologic titer was
      lower and continued to decline in eradication success cases whose mean residual
      titer ratio (100% x follow-up titer/initial titer) was lower than that of
      eradication failure cases (57.1% +/- 14.6% vs 107.1% +/- 24.1%, p < 0.001). The
      mean residual titer ratio also disclosed an upward trend as the density of H.
      pylori increased (density of H. pylori 1 to 5: 57.5%, 66.6%, 73.5%, 75.3%, 81.8%,
      respectively). CONCLUSIONS: We suggest routine gastric biopsy to detect both the
      presence of H. pylori and its density inasmuch as quantitative results may
      predict the usefulness of triple therapy. The higher the H. pylori density, the
      less effective triple therapy will be at successful eradication of H. pylori.

PMID- 8979060
TI  - Does intrabiliary pressure predict basal sphincter of Oddi pressure? A study in
      patients with and without gallbladders.
AB  - BACKGROUND: The endoscopic measurement of sphincter of Oddi pressure is a
      technically difficult procedure requiring significant expertise. Intrabiliary
      pressure is technically easy to measure. Furthermore, since it is believed that
      the pathogenesis of pain in patients with sphincter of Oddi dysfunction is
      attributable to increased intrabiliary pressure, its measurement may be more
      clinically relevant than measurement of sphincter of Oddi pressure. METHODS:
      Intrabiliary pressures were blindly measured in 54 patients who had sphincter of
      Oddi manometry for abdominal pain. RESULTS: In all patients intrabiliary pressure
      was significantly higher in patients with sphincter of Oddi dysfunction than
      those with normal sphincter of Oddi pressure (19.6 +/- 2.2 vs 9.6 +/- 1.2 mm Hg;
      p < 0.01). These findings were similar when patients were stratified according to
      presence of intact gallbladder (19.3 +/- 1.6 vs 8.8 +/- 1.4; p < 0.01) and to
      patients without a gallbladder (20.1 +/- 3.8 vs 12/1 +/- 1.3; p = .034). There
      was positive correlation between intrabiliary pressure and sphincter of Oddi
      basal pressure. This correlation was significant both in patients with and
      without gallbladders. CONCLUSIONS: These data suggest that increased intrabiliary
      pressure may be a useful surrogate marker of sphincter of Oddi dysfunction.

PMID- 8979061
TI  - Partial regression of Barrett's esophagus by long-term therapy with high-dose
      omeprazole.
AB  - BACKGROUND: Barrett's esophagus is mainly regarded as an acquired condition
      related to increased gastroesophageal reflux. Thus it is conceivable that
      abolition of acid reflux would lead to its regression. The aim of this study was
      to assess whether long-term treatment with high-dose omeprazole (60 mg/day)
      produces a consistent control of gastric acid production and normalizes the
      esophageal acid exposure, thus reducing the length of Barrett's epithelium.
      METHODS: Fourteen patients (8 men and 6 women, mean age 52 years) with histologic
      diagnosis of columnar epithelium longer than 3 cm in the distal part of the
      esophagus were enrolled and began receiving 60 mg of omeprazole in a single daily
      morning dose. Before therapy and after 6 and 12 months of therapy, all patients
      had endoscopy with four-quadrant biopsies at 2 cm intervals. A 24-hour
      esophagogastric pH recording was performed at entry and after 10 days, 6 months,
      and 12 months of treatment in all patients. RESULTS: The initial length of
      Barrett's epithelium (4.5 +/- 1.9 cm) was significantly reduced after 6 months
      (3.1 +/- 1.1; p < 0.01) and 12 months (2.1 +/- 1.6; p < 0.005) of treatment.
      Values were significantly lower at 12 than at 6 months (p < 0.03). The 24-hour
      mean gastric pH after 10 days (5.89 +/- 0.58), 6 months (5.71 +/- 0.55), and 12
      months (5.54 +/- 0.76) of therapy was always higher (p < 0.001) than the basal
      level (1.9 +/- 0.49). No significant difference in gastric pH was seen over the
      treatment period. The 24-hour mean percent of time in which pH in the esophagus
      was below 4.0 decreased significantly (p < 0.001) from a basal rate of 29.4% to
      3.5%, 3.0%, and 4.9% in the various time intervals of therapy. There was a
      normalization of esophageal acid exposure in all patients but two. CONCLUSIONS:
      It can be concluded that the antisecretory effect of 60 mg/day of omeprazole is
      consistent and is kept constant throughout the entire 1-year treatment period.
      The consequent normalization of esophageal acid exposure in almost all patients
      in our series led to a partial, but significant, regression in the length of
      Barrett's epithelium.

PMID- 8979062
TI  - Staging of ampullary and pancreatic carcinoma: comparison between endosonography
      and surgery.
AB  - BACKGROUND: The aim of the study was to update our previously published data on
      the clinical TNM staging of ampullary and pancreatic carcinoma by endosonography.
      METHODS: Endosonography was performed in 70 patients with pancreatic cancer and
      in 32 patients with ampullary carcinoma. TNM staging was carried out before
      surgery and compared with findings of histology and/or surgery. RESULTS:
      Endosonography was accurate in staging the depth of tumor invasion. Early-stage
      carcinomas could be distinguished from advanced cancers. Nonresectability was
      accurately assessed on the basis of vascular involvement using real-time
      ultrasound. Tumor compression due to peritumoral pancreatitis and direct tumor
      invasion into the base of the mesocolon could not be diagnosed by endosonography.
      The overall accuracy in tumor staging for pancreatic and ampullary carcinomas was
      83.6% and 84.4%, respectively. Endosonography was accurate in diagnosing regional
      lymph node metastases but not accurate in defining nonmetastatic lymphadenopathy
      and distant metastases. CONCLUSION: Endosonography was accurate in staging tumor
      stage and lymph node metastases. Minimally invasive methods of resection for
      superficial ampullary cancers should be based on endosonography staging.

PMID- 8979064
TI  - Endoscopic ultrasound-assisted band ligation: a new technique for resection of
      submucosal tumors.

PMID- 8979063
TI  - Endosonographic characterization of duodenal elevated lesions.
AB  - BACKGROUND: Endoscopic diagnosis of duodenal elevated lesions is problematic for
      two reasons. Endoscopic biopsy often fails to confirm a histologic diagnosis of
      submucosal lesions. Moreover, a biopsy specimen is often insufficient to verify a
      differential diagnosis of mucosal lesions. In this study, we evaluated the
      usefulness of endosonography in the resolution of these problems. METHODS: The
      endoscopic and endosonographic features of 15 duodenal elevated lesions that had
      been confirmed histologically in our hospital were reviewed retrospectively.
      RESULTS: Of the 15 cases, 8 were submucosal lesions (lipoma, Brunner's gland
      hyperplasia, lymphangioma, carcinoid tumors, leiomyoma, and malignant lymphoma);
      the rest were mucosal lesions. A correct histologic diagnosis based on endoscopic
      biopsies was obtained in only 6 cases (three submucosal lesions and three mucosal
      lesions). On the other hand, ultrasonography was useful in the characterization
      of all submucosal lesions based on their echo level, layer of origin, and tissue
      homogeneity. As for mucosal lesions, the depth of infiltration was correctly
      estimated with endosonography. Either endoscopic resection or surgery was
      selected on the basis of endosonographic information. CONCLUSIONS: We conclude
      that endosonography is useful in the differential diagnosis of submucosal lesions
      and in determining suitable treatment methods for duodenal mucosal and submucosal
      lesions.

PMID- 8979065
TI  - Endoscopic ultrasonography for diagnosing blunt pancreatic trauma.

PMID- 8979066
TI  - Suction sclerotherapy for the treatment of esophageal varices.

PMID- 8979067
TI  - Thalidomide treatment for idiopathic esophageal ulcers in patients with HIV.

PMID- 8979068
TI  - Upper gastrointestinal tract fistulae: endoscopic obliteration with fibrin
      sealant.

PMID- 8979070
TI  - Endoscopic ultrasound-directed pancreatography.

PMID- 8979069
TI  - Staging of non-Hodgkin's gastric lymphoma with endosonography-guided fine-needle
      aspiration biopsy and flow cytometry.

PMID- 8979071
TI  - Self-expanding metal stent for obstructing adenocarcinoma of the sigmoid.

PMID- 8979072
TI  - The use of a wire mesh stent in treating biliary obstruction caused by shrapnel.

PMID- 8979073
TI  - Endosonography in colitis cystica profunda and solitary rectal ulcer syndrome.

PMID- 8979074
TI  - Is your sphincterotomy really safe--and necessary?

PMID- 8979075
TI  - Gastrointestinal Endoscopy: roar lion, roar.

PMID- 8979076
TI  - Eradication of Helicobacter pylori as the first step in the treatment of peptic
      stenosis.

PMID- 8979077
TI  - Rapid and simple biliary stent deployment.

PMID- 8979078
TI  - Unusual ERCP appearance of obstructive jaundice caused by pancreatic cancer.

PMID- 8979079
TI  - Extracorporeal shock-wave lithotripsy for gallstone ileus.

PMID- 8979080
TI  - Esophageal dilation in the sitting, sedated patient is safe and effective.

PMID- 8979081
TI  - Topical anesthesia and urease tests.

PMID- 8979082
TI  - Use of cricoid pressure to facilitate gastric insufflation and stop hiccoughs
      during gastroscopy.

PMID- 8979083
TI  - Prospective study on the detection of insulinomas by endoscopic ultrasound.

PMID- 8979084
TI  - Early antibiotic treatment in acute necrotizing pancreatitis.

PMID- 8979085
TI  - Identification of a SPH element in the distal region of a human U6 small nuclear
      RNA gene promoter and characterization of the SPH binding factor in HeLa cell
      extracts.
AB  - Vertebrate small nuclear RNA (snRNA) gene promoters contain a distal, enhancer
      like region that is composed of an octamer motif adjacent to at least one other
      element. Here we show that a human U6 snRNA distal region contains a SPH motif
      previously found in several chicken snRNA gene enhancers and the 5'-flanking
      region of vertebrate selenocysteine tRNA genes. SPH binding factor (SBF) was
      detected in either chicken or HeLa cell extracts that could bind SPH elements in
      a species-independent manner. Both human and chicken SBF required divalent cation
      to bind effectively to DNA. DNase I footprinting experiments indicated that human
      SBF specifically protected the human U6 SPH element. Furthermore, a SBF
      polypeptide of approximately 85 kDa was detected in both HeLa and chicken
      extracts following ultraviolet light-mediated cross-linking to human U6 or
      chicken U4 SPH elements. A part of the human U6 SPH element was quite sensitive
      to mutation, as demonstrated by both specific protein binding and transcription
      assays. From these data it is apparent that the distal regions of some RNA
      polymerase III- and RNA polymerase II-transcribed small RNA promoters are
      virtually identical in composition, and their mechanisms of transcriptional
      activation are possibly quite similar.

PMID- 8979086
TI  - Analysis of the negative transcriptional regulatory element in the angiotensin
      converting enzyme gene.
AB  - We have characterized the sequence requirements and the protein binding
      properties of the previously identified transcriptional negative element present
      in the rabbit angiotensin-converting enzyme (ACE) gene. DNase footprinting
      experiments revealed that within the negative element (-715 to -610) several
      regions interact with proteins present in the nuclear extracts of ACE-expressing
      and -nonexpressing cell lines. Transfection analysis using the heterologous beta
      actin promoter and mutated negative elements demonstrated that the SP1 site, the
      collagen-silencer-like sequence, and the inverted repeat elements are dispensable
      for their functioning. Deletion of the region between -692 to -668, however,
      completely eliminated the activity of the negative element, and mutation of the
      synapsin-silencer-like sequence present within this region vastly reduced it.
      This region (-692 to -668) by itself, when present in two copies, could
      effectively repress the activity of the beta-actin promoter. The same point
      mutations in the silencer element that destroyed its action on the beta-actin
      promoter greatly increased the transcriptional efficiency of the native ACE
      promoter. Electrophoretic mobility shift assay using the -692 to -668 ACE
      silencer sequence demonstrated the formation of a DNA/protein complex. UV cross
      linking of the components of this complex revealed the presence of one prominent
      protein of approximately 21.5 kDa. This protein may be responsible for mediating
      the transcriptional-repressing activity of the ACE negative element. Homology
      between the ACE silencer and neuronal silencer consensus sequence, together with
      the promoter- and tissue-independent function of the the ACE silencer, suggests
      this element may bind a member of a large family of common negative regulatory
      transcription factors.

PMID- 8979087
TI  - The human aldehyde dehydrogenase 3 gene (ALDH3): identification of a new exon and
      diverse mRNA isoforms, and functional analysis of the promoter.
AB  - Expression of the human ALDH3 gene is regulated in a tissue-dependent
      constitutive as well as drug-inducible manner. We identified a new 5'-noncoding
      exon (exon 1) existing at about 3 kilobase pairs (kb) upstream from the first
      coding exon (exon 2) of the human ALDH3 gene. Analysis of ALDH3 mRNA revealed the
      existence of several isoforms with different 5' regions resulting from i) usage
      of multiple transcriptional initiation sites of the new exon 1, ii) usage of
      alternative splice acceptor sites at the 3' end of the new intron 1, and iii)
      alternative splicing out of exon 2. Usage of alternative splice acceptor sites
      was only found in tissues expressing ALDH3 constitutively, but not in Hep G2
      induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Nucleotide sequence
      analysis and chloramphenicol acetyltransferase (CAT) expression studies showed
      that a strong promoter region exists at nucleotide (nt) positions -216 to +54 of
      the gene. Repression activities were found upstream of the -216/+54 region.
      Several putative drug-inducible elements exist in the regulatory region. A
      possible regulatory mechanism for tissue-specific constitutive and inducible
      expression of the human ALDH3 gene is discussed.

PMID- 8979088
TI  - A base substitution in the amino acid acceptor stem of tRNA(Lys) causes both
      misacylation and altered decoding.
AB  - In 1984, our laboratory reported the characterization of the first misacylated
      tRNA missense suppressor, a mutant Escherichia coli lysine tRNA with a C70 to U
      base change in the amino acid acceptor stem. We suggested then that the
      suppressor tRNA, though still acylated to a large extent with lysine, is
      partially misacylated with alanine. The results reported in this article
      demonstrate that is the case both in vitro and in vivo. For the in vitro studies,
      the mutant tRNA species was isolated from the appropriate RPC-5 column fractions
      and shown to be acylatable with both lysine and alanine. For the in vivo
      demonstration, use was made of a temperature-sensitive alaS mutation, which
      results in decreasing acylation with Ala as the temperature is increased,
      resulting ultimately in lethality at 42 degrees C. The alaSts mutation was also
      used to demonstrate that the ability of the same missense suppressor, lysT(U70),
      to suppress a trpA frameshift mutation is not affected by the Ala-acylation
      deficiency. We conclude that the misacylation and altered decoding are two
      independent effects of the C70 to U mutation in tRNA(Lys). The influence of an
      alteration in the acceptor stem, which is in contact with the large (50S)
      ribosomal subunit, on decoding, which involves contact between the anticodon
      region of tRNA and the small (30S) ribosomal subunit, may occur intramolecularly,
      through the tRNA molecule. Alternatively, the U70 effect may be accomplished
      intermolecularly; for example, it may alter the interaction of tRNA with
      ribosomal RNA in the 50S subunit, which may then influence further interactions
      between the two subunits and between the 30S subunit and the anticodon region of
      the tRNA. Preliminary evidence suggesting some form of the latter explanation is
      presented. The influence of a single nucleotide on both tRNA identity and
      decoding may be related to the coevolution of tRNAs, aminoacyl-tRNA synthetases,
      and ribosomes.

PMID- 8979090
TI  - Plasma endothelin-1 levels during asphyxia in the fetal goat.
AB  - The changes in fetal carotid arterial plasma levels of endothelin-1,
      catecholamines, PO2, PCO2 and pH were measured after intermittent repetitive
      umbilical cord occlusion in late gestation pregnant goats (n = 9). Endothelin-1
      levels increased to 3.58 +/- 0.28 pg/ml immediately after the onset of fetal
      hypoxia, a level significantly higher than the respective values in the control
      period (p < 0.05). The elevation of fetal plasma endothelin-1 levels correlated
      inversely with carotid arterial PO2 (r = -0.41, p < 0.05) and pH (r = - 0.43, p <
      0.05). The results suggest that increased endothelin-1 levels may contribute to
      the maintenance of the fetal circulation during fetal asphyxia.

PMID- 8979089
TI  - TATA box and Sp1 sites mediate the activation of c-myc promoter P1 by
      immunoglobulin kappa enhancers.
AB  - In Burkitt's lymphoma (BL) cells the proto-oncogene c-myc is transcriptionally
      activated by chromosomal translocation to the immunoglobulin (Ig) gene loci. This
      activation is characterized by preferential transcription from the c-myc promoter
      P1 and accomplished by juxtaposed Ig enhancer elements. To identify promoter
      elements required for enhancer-activated P1 transcription, we studied the
      activation of c-myc reporter gene constructs by the Ig kappa intron and 3'
      enhancers. Deletion analysis defined the core promoter with a TATA box and two
      adjacent GC/GT boxes upstream sufficient for basal and enhancer-activated
      transcription. Gel retardation assays revealed Sp1's binding affinity to the
      GC/GT box proximal to the TATA box to be higher than to the distal one. This
      difference correlated well with the resulting levels of transcription mediated by
      Sp1 in contransfection experiments in BL and Sp1-deficient SL2 cells. Sp3 also
      bound to the core promoter in vitro, but failed to transactivate in vivo.
      Mutation of the distal Sp1 site moderately affected basal transcription
      concomitant with a modest decrease in enhancer stimulation. Mutation of the
      proximal Sp1 site almost entirely abolished basal as well as enhanced
      transcription. A considerable level of basal transcription was maintained upon
      mutation of the TATA box, whereas enhancer-activated transcription largely was
      abolished. Stable transfection of the BL cell line Raji with constructs
      containing core promoter mutations confirmed that the proximal Sp1 site and the
      TATA box are essential for the activation of promoter P1 by the Ig kappa
      enhancers.

PMID- 8979091
TI  - Vaginal birth following unmonitored labor in patients with prior cesarean
      section.
AB  - Following a previous cesarean section, trial labour followed by spontaneous birth
      is currently popular but is still debatable. In an effort to assess the risks of
      unmonitored labor, the outcomes of 165 patients with previous cesarean section
      who delayed coming to hospital were reviewed. Seventy-one patients were allowed
      to continue labor and 62 achieved successful vaginal delivery, a success rate of
      87.3%. Sixty-one of 71 patients had an unknown uterine scar type prior to birth
      and, of these, 57 were delivered vaginally. The scar separation rate of this
      group was found to be 3.5% and the overall scar separation rate in our patients
      was 3.6%. Other than scar separation and febrile morbidity, no maternal morbidity
      or mortality was observed. The vast majority (98.4%) of infants delivered
      vaginally had 5-min Apgar scores of 7 or greater. We suggest that increasing the
      use of trial labor in patients with prior cesarean section, even in the presence
      of an unknown scar, may reduce the number of patients laboring in an unmonitored
      environment who wish to give birth vaginally.

PMID- 8979092
TI  - Thyroid function in early normal pregnancy: transient suppression of thyroid
      stimulating hormone and stimulation of triiodothyronine.
AB  - In order to determine the effect of gestation on thyroid function in healthy
      subjects, we have prospectively evaluated thyroid function in pregnant
      individuals undergoing termination of pregnancy, and repeated the tests 2-3
      months later. Venous blood was tested for human chorionic gonadotropin (hCG),
      thyroid-stimulating hormone (TSH), free thyroxine (FT4) and total
      triiodothyronine (TT3). Early pregnancy thyroid function tests showed a
      significant decrease (p < 0.001) in TSH and a significant increase (p < 0.001) in
      TT3 as compared to the nonpregnant state; FT4, however, did not change
      significantly. In 8 (11.2%) pregnant subjects, TT3 levels were above the normal
      range for nonpregnant controls. Elevated thyroid function in early pregnancy is
      transient, and does not usually warrant antithyroid treatment. Thus, any
      conclusion regarding thyroid function in early pregnancy should be based on
      pregnant controls rather than general population controls.

PMID- 8979093
TI  - Effect of antihypertensive therapy in preeclampsia on levels of serum interleukin
      4.
AB  - We investigated the effects of antihypertensive therapy on serum levels of
      interleukin-4 using InterTest-4 ELISA in 25 preeclamptic women; 14 were placed on
      treatment, while 11 were not. Comparison was made with 14 non-preeclamptic
      pregnant controls. Interleukin-4 levels were significantly lower in the controls
      than in the treated preeclamptic women (p < 0.001): 68.6 +/- 10.9 versus 106.1 +/
      13.2, 64.7 +/- 9.6 versus 119.8 +/- 11.4, 90.2 +/- 9.1 versus 124.3 +/- 15.7,
      and 65.6 +/- 3.6 versus 109.7 +/- 11.4 pg/ml, during antepartum, early
      intrapartum, late intrapartum and postpartum periods, respectively. No
      significant differences were detected between the therapy and no therapy
      subgroups (p > 0.05). This shows that antihypertensive therapy has no effect on
      interleukin-4 levels.

PMID- 8979094
TI  - Vertebral bone mineral density in postpartum women.
AB  - The purpose of this study was to measure the bone mineral density of the lumbar
      spine (L2-L4) in healthy postpartum women following term delivery, and to
      evaluate factors associated with bone mineral density. Using dual energy X-ray
      absorptiometry, the bone mineral density of the lumbar spine was determined
      during 1 year in 123 healthy postpartum Japanese women following term delivery.
      The mean bone mineral density of the lumbar spine was 1.007 +/- 0.108 g/cm2
      (range 0.731-1.252 g/cm2). Thus, there were wide inter-individual differences.
      Also, this result was in agreement with the peak bone mass previously reported
      for other Japanese women. Multiple regression analysis and linear regression
      analysis showed that weight and body mass index were each significantly
      correlated with bone mineral density of the lumbar spine. Age, parity, height,
      and baby's birth weight were not contributory.

PMID- 8979095
TI  - Raised circulating levels of interleukin-6 in women with an intrauterine
      contraceptive device.
AB  - The aim of this study was to determine whether the presence of an intrauterine
      contraceptive device (IUCD) causes a systemic elevation of interleukin-6 (IL-6).
      The control group comprised 29 women with normal cycles and who were not using
      any form of contraception and the study group comprised 74 women who had had an
      IUCD in place for 10-24 months. Of these, 45 had intermenstrual bleeding.
      Systemic IL-6 was undetectable (minimum detection limit of the assay is 5 pg/ml)
      in the control but was raised in 20% of the women fitted with an IUCD (p < 0.01).
      There was no difference between IL-6 levels in IUCD users who had intermenstrual
      bleeding and those who did not. These results suggest that the effects of chronic
      IUCD usage may not be limited to the endometrium.

PMID- 8979096
TI  - Selection of criteria for the treatment of ovarian cysts on the bases of
      ultrasound and cytology.
AB  - The major objective of the present study was to determine whether leakage of
      ovarian cyst cells occurs when the cysts are punctured inside a container with
      saline. Other subjectives were to determine the sensitivity and specificity of
      cytology in the differentiation between malignant and benign cysts by comparing
      cytology data with histology data, and also to determine whether ultrasound can
      provide consistent evidence for predicting whether the cyst is benign or
      malignant, thus permitting the selection of patients with benign cysts for
      puncture rather than surgical exeresis. A cytologic study was carried out on the
      contents of 62 ovarian cysts diagnosed by ultrasound and clinical examination,
      and excised from 51 patients submitted to exploratory laparotomy. The cyst was
      excised and immersed in a container with saline outside the surgical field. The
      cyst was punctured and its contents aspirated through the wall of the container.
      Five samples were obtained for cytology: (1) presurgical abdominal wash; (2)
      saline before cyst puncture; (3) fluid from the punctured cyst; (4) saline after
      cyst puncture, and (5) postoperative abdominal wash. The materials obtained were
      submitted to centrifugation and slides of the precipitate were prepared for
      cytology. A total of 248 slides were studied. Slides of cysts with good
      cellularity were stained with silver to study the nucleolar organizer regions.
      Analysis using Kappa statistics showed excellent agreement between the cytologic
      and histologic diagnoses (p < 0.001). The sensitivity of the cytologic study of
      the cyst was 75% and the specificity 100%, with a positive predictive value of
      100%, a negative predictive value of 92%, and 93% accuracy. The present results
      led us to conclude that cell leakage into physiological saline occurred after
      puncture and that cytologic study of cysts valuable in the diagnosis of benign
      and malignant processes.

PMID- 8979097
TI  - Laparoscopically assisted vaginal hysterectomy as an alternative to abdominal
      hysterectomy. A pilot study.
AB  - Laparoscopically assisted vaginal hysterectomy (LAVH) allows for conversion of
      some abdominal hysterectomies to a vaginal route. LAVH may be particularly useful
      when adnexectomy is indicated. In this study the authors evaluate the results
      obtained in a series of 21 patients prospectively selected for LAVH. The mean
      operative time was 96 min (range 58-155), with an estimated blood loss of 218 ml
      (range 50-510). The mean uterine weight was 320 g (range 105-610). Intraoperative
      complications were limited to one case of bladder injury which occurred during
      the vaginal phase of the procedure. No patient required heterologous blood
      transfusion. No postoperative complications were observed. The average length of
      hospitalisation was 4.4 days (range 2-9). The authors conclude that LAVH allows
      for conversion of a significant number of abdominal hysterectomies to a vaginal
      route and that with respect to the former it is definitely less costly since it
      allows for earlier hospital discharge and resumal of a normal lifestyle.

PMID- 8979098
TI  - Electro-oviductogram: a study of the electromechanical activity of the canine
      oviduct.
AB  - The purpose of this communication was to study the electromechanical activity of
      the oviduct aiming at the characterization of a normal 'electro-oviductogram'
      (EOG). The oviduct of 14 bitches was exposed and 3 monopolar silver-silver
      chloride electrodes were sutured to the duct serosa. The oviduct pressure was
      also measured. Direction of propagation of the electric activity was assessed by
      duct myotomies. Slow waves or pacesetter potentials (PPs) were recorded from the
      3 electrodes of each dog. They were identical from the 3 electrodes, had a
      regular rhythm and were reproducible. The PPs were followed by bursts of action
      potentials (APs) which were associated with increased oviduct pressure. PPs and
      APs were recorded from electrodes proximal but not distal to the oviduct myotomy,
      indicating that they were propagated from the fimbrial end of the oviduct towards
      the uterus. A 'pacemaker' initiating these waves might exist at this fimbrial
      end. The increased oviduct pressure associated with APs might point to a
      contractile activity that may be responsible for initiating the oviduct
      peristaltic activity. In conclusion, the current study could characterize an EOG
      for the normal canine oviduct. It is suggested that, after further studies, the
      EOG may be included as an investigative tool in the diagnosis of oviduct
      disorders.

PMID- 8979099
TI  - The association of age and sexual history with the severity of the histological
      findings in women with cervical intraepithelial neoplasia.
AB  - We examined the demographic and behavioral data of 203 patients with histological
      diagnosis of cervical intraepithelial neoplasia (CIN) to assess putative
      predictors of the most severe alterations (CIN grade III). The variables
      significantly associated with the histological diagnosis of CIN III were time
      since first intercourse (odds ratio 5.33, 95% CI 1.80-16.15), time since menarche
      (odds ratio 4.62, 95% CI 1.39-16.05) and age (odds ratio 2.48, 95% CI 1.32-4.67).
      After multivariate analysis, the only independent variable still associated with
      CIN III was the time since first intercourse (odds ratio 6.11, p < 0.05). It is
      concluded that, in patients with recently diagnosed CIN, the time since first
      intercourse-rather than age, age at first intercourse or lifetime number of sex
      partners-is the information best associated with the severity of the disease.

PMID- 8979100
TI  - MIB 1 immunostaining in cervical intraepithelial neoplasia: prognostic
      significance in mild and moderate lesions.
AB  - OBJECTIVE: MIB 1 is a new monoclonal antibody which recognizes nuclei of
      proliferating cells throughout the cell cycle except during the G0 and early G1
      phases. In the present study we analyzed the MIB 1 immunostaining as an index of
      cellular proliferation in cervical intraepithelial neoplasia (CIN) and
      microinvasive carcinoma, with the aim to identify a relationship with the degree
      of dysplastic lesion and the risk of neoplastic progression. A correlation
      between the MIB 1 index and human papillomavirus (HPV) DNA presence was also
      investigated METHODS: Cervical bioptic samples were consecutively obtained from
      86 women who attended our Colposcopic Service from January 1993 to June 1994,
      because of abnormal pap smears suspicious for cervical dysplasia and/or HPV
      infection. On histologic evaluation, 41 women had CIN, 23 cervical condyloma, and
      22 squamous metaplasia. Ten patients with microinvasive squamous cervical
      carcinoma, matched for age and demographic characteristics, were selected from
      our series of cervical carcinomas and immunohistochemically analyzed. The
      expression of primary tumor cellular proliferation was immunohistochemically
      evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on
      microwave oven-processed formalin-fixed paraffin-embedded tissue. Positive
      staining was expressed as the percentage of positive cells per 10(3) counted
      dysplastic cells for each case. RESULTS: A progressive significant increase in
      positive MIB 1 immunostaining was observed from squamous metaplasia to
      microinvasive carcinoma throughout the CIN lesions (p < 0.001). Considering only
      CINs, the MIB 1 index showed a significant increase with respect to CIN degrees
      (p < 0.001); no correlation was found between MIB 1 immunostaining and HPV
      infection, and lesion size. By analyzing the MIB 1 index with respect to CIN
      outcome in mild and moderate dysplasias, regressive lesions had lower values of
      MIB 1 immunostaining, while persistent and progressive lesions presented
      significantly higher positivity (p < 0.001). CONCLUSIONS: Our data demonstrated:
      (1) that positive MIB 1 immunostaining increased progressively from squamous
      metaplasia to CIN and microinvasive carcinoma, suggesting that neoplastic
      transformation is associated with a dysfunctional proliferation of cervical
      epithelium; (2) that there was a significant correlation between the MIB 1 index
      and CIN degree but not with respect to HPV DNA presence, and (3) that MIB 1
      immunostaining might be useful for a clinical evaluation of mild and moderate
      dysplastic lesions. However, a much larger study needs to be done over a longer
      period of time to truly determine the value of the technique in prognostically
      predicting which lesions might or might not regress.

PMID- 8979101
TI  - Serum levels of cytokeratin 19 fragments in cervical cancer.
AB  - Serum levels of a cytokeratin 19 fragment, Cyfra 21-1, were measured using an
      immunoradiometric assay in 33 women before initial treatment and in 8 women with
      recurrent tumor. The serum level of Cyfra 21-1 was significantly increased in
      women with tumors of advanced stage (FIGO) and those with recurrence. The
      incidence of positivity for Cyfra 21-1 tended to increase with tumor spread.
      Compared with squamous cell carcinoma (SCC) antigen, the sensitivity of Cyfra 21
      1 was comparable to that of SCC antigen. The serum level of Cyfra 21-1 and that
      of SCC antigen showed a positive correlation. While the use of the serum Cyfra 21
      1 level may be limited in cervical cancer by its relatively low sensitivity, a
      combination assay of Cyfra 21-1 and SCC antigen may be useful in the diagnosis
      and follow-up of patients with cervical squamous cell carcinoma.

PMID- 8979102
TI  - Placental isoferritin patterns during first-trimester intrauterine gestation.
AB  - In this study, serum placental ferritin (PLF) levels were measured among 33
      pregnant women with normal, singleton, ongoing first-trimester gestations and
      compared with 22 nonbleeding, missed and 14 incomplete abortions. Diagnoses were
      based on clinical, sonographic, endocrinologic and histopathologic criteria. At
      admission and before uterine evacuation of the pregnancy products, venous blood
      was collected from the groups for PLF determination. The mean +/- SD serum PLF
      levels were 18 +/- 14, 21 +/- 37, and 3.9 +/- 6.2 U/ml in normal gestations,
      missed and incomplete abortions, respectively. Significant differences in PLF
      levels were found among normal pregnancies and incomplete abortions (p < 0.05),
      whereas borderline significance was found in the missed abortion group (p =
      0.53). No correlation was found between serum beta hCG and PLF for the various
      pregnancy groups. Low PLF levels in pathologic gestation may reflect abnormal
      trophoblastic activity. Whether these play a causal role or are the casual
      outcome of pathologic gestation should be the subject of further evaluation.

PMID- 8979103
TI  - Spontaneous perforated pyometra presenting as pneumoperitoneum.
AB  - BACKGROUND: Spontaneous perforated pyometra presenting as pneumoperitoneum is
      extremely rare. CASE REPORT: An 80-year-old Japanese female with spontaneous
      perforating pyometra presenting as pneumoperitoneum is reported. The patient came
      to our institute with severe abdominal pain. Routine abdominal examination showed
      muscular defense, and plain chest roentgenograms revealed infradiaphragmatic free
      gas. Subsequent computed tomography also demonstrated pneumoperitoneum.
      Laparotomy was performed on the basis of a tentative diagnosis of perforation of
      the gastrointestinal tract but revealed a perforated pyometra. A simple
      hysterectomy was performed. The histological diagnosis of the surgical specimen
      was acute endometritis without neoplasm. The present report is the third case of
      spontaneous perforated pyometra with pneumoperitoneum to date. CONCLUSION:
      Although uterine disease presenting as pneumoperitoneum is rare in elderly
      patients with an acute abdomen, the possibility of a perforated pyometra should
      be considered in the differential diagnosis.

PMID- 8979104
TI  - A case of Pendred's syndrome presenting with amenorrhea.
AB  - Pendred's syndrome is manifested by congenital sensorineural deafness in
      association with familial goiter due to defective organic binding of iodine in
      the thyroid gland. The majority of patients with Pendred's syndrome are
      euthyroid. We report on an unusual case of a patient with Pendred's syndrome
      presenting with amenorrhea and late-onset hypothyroidism.

PMID- 8979105
TI  - Urethral caruncle: an unusual presentation of ovarian tumour.
AB  - Secondary female urethral cancer presenting as urethral caruncle is extremely
      rare. We report a primary ovarian adenocarcinoma in a 78-year-old female patient
      presented initially as a urethral caruncle. This case represents the first
      reported case in the world literature. The clinical features, investigations and
      pertinent literature are reviewed.

PMID- 8979106
TI  - Mechanisms, markers and management of hypercoagulable states.
AB  - Information on hypercoagulability can be achieved through the measurement of
      peptides that are generated when zymogens are activated, of the active enzymes,
      or of the complexes that form in the circulation when enzymes are inactivated by
      their plasmatic inhibitors. These assay methods have dramatically improved our
      understanding of the mechanisms which regulate coagulation in health and disease.
      However, their choice and use as predictors of thrombotic events and to monitor
      anticoagulant treatment still need to be defined in prospective clinical trials.

PMID- 8979107
TI  - Molecular basis for protein C hereditary deficiency.
AB  - The clinical presentation of hereditary protein C deficiency is highly variable.
      Homozygosity and compound heterozygosity have been linked to severe thrombotic
      complications early in the life. Heterozygous patients have a moderate form of
      the disease with deep venous thrombosis during adulthood. In the French
      population, we found 53 different mutations in 90 families. The amount of the
      protein C produced by the mutant allele as well as the genetic status partly
      account for the variable clinical expression. Other gene may also be involved:
      Arg 506 to Gln factor V mutation shows a frequency of 10 to 20% in symptomatic
      protein C deficient patients. Some protein C gene mutations are associated with a
      non functional circulating protein; most of them are located in the GLA domain
      and in the serine protease domain. The biochemical characterization of a few of
      theses variants has shown the important role of some amino acids on the
      activation and the mechanism of action of protein C.

PMID- 8979108
TI  - Platelet-polymorphonuclear leukocyte functional interactions: role of adhesive
      molecules.

PMID- 8979109
TI  - Consequences of transcellular biosynthesis of leukotriene C4 on organ function.
AB  - Formation of eicosanoids is a special mode of cell communication whereby
      production of eicosanoids by mixed cell populations differs from that expected
      from each individual cell. Transcellular biosynthesis of leukotriene C4 occurs
      via transfer of the reactive intermediate leukotriene A4 from neutrophils to
      vicinal acceptor cells devoid of 5-lipoxygenase activity such as platelets or
      vascular cells. Evidence for the in vivo relevance of transcellular eicosanoid
      metabolism results from experiments using the isolated beating rabbit heart
      perfused with activated neutrophils. The resultant leukotriene C4 synthesis is
      timely related to the pressor response of the coronary arteries and inflammatory
      damage of the heart by edema formation and neutrophil infiltration into the
      organ. Blockade of leukotriene C4 synthesis by 5-lipoxygenase inhibitors or
      leukotriene C4 actions by respective receptor antagonists facilitated significant
      protective effects. Further confirmation of the potential role of LTC4 in
      myocardial ischemia comes from in vivo studies in the rabbit.

PMID- 8979110
TI  - Injury models of the vascular endothelium: apoptosis and loss of
      thromboresistance induced by a viral protein.
AB  - Endothelial injury caused by viruses usually involves viral replication or
      transformation. We report a novel mechanism of endothelial damage by a toxic
      viral protein. We have isolated a new retrovirus from hemangiosarcomas which
      appeared among layer hens. The isolated avian hemangiosarcoma virus (AHV) is
      capable of inducing hemangiomas in hens in-vivo and causes a cytopathic effect
      (CPE) and loss of thromboresistance in cultured bovine aortic endothelial cells
      (BAEC). These effects do not require viral replication and can be induced by
      purified AHV envelop glycoprotein (gp85). AHV causes CPE in BAEC through a
      typical programmed cell death (apoptosis). Quiescent G0/G1-BAEC are much more
      sensitive to AHV induced apoptosis than actively dividing cells. These
      experiments demonstrate the capacity of viral proteins to affect the integrity
      and functionality of vascular endothelial cells.

PMID- 8979111
TI  - Dietary fatty acids in athero-thrombogenesis: influence of palm oil ingestion.
AB  - Dietary experiments, performed in metabolic wards, gave rise to predictive
      regression equations relating changes of plasma cholesterol concentration to the
      intake of fatty acids of the diet. It has been established that polyunsaturated
      fatty acids diminish and most saturated fatty acids increase plasma cholesterol
      concentration. This information led to expect that dietary use of palm oil may
      induce an unfavorable plasma lipoprotein profile. This has not been the case as
      shown in various dietary experiments. The reasons for this discrepancy is
      discussed. The influence of palm oil enriched diets on prothrombotic variables
      show that platelets are not affected in their function during prolonged dietary
      intervention. It is important to continue research on the effects of palm oil
      based diet on plasma fibrinogen, factor VII. There is still discordant
      information in this field.

PMID- 8979112
TI  - Which experimental model to choose to study arterial thrombosis and evaluate
      potentially useful therapeutics?
AB  - The use of experimental models of arterial thrombosis both in vivo and ex vivo in
      animals and ex vivo in humans is an obligatory step for the understanding of
      mechanisms involved in thrombogenesis as well as in the evaluation of anti
      thrombotic therapeutics. Arterial thrombogenesis is a complex phenomenon which
      involves multiple systems, mechanisms and parameters. Therefore studies of
      thrombogenesis from a pathological as well as a therapeutic point are necessary
      for understanding this problem in its entirety. For these reasons, it is
      necessary to use models as representative as possible of the human pathological
      condition. Besides these theoretical requirements, practical needs have also to
      be fulfilled (accessibility of the models, adaptation to the type of the
      technique to different animal model and/or of the size of the animal to the
      amount of molecule available, cost...) which necessarily lead to some
      compromises. In this review we have tried to underline the criteria for the
      choice, characteristics, advantages and disadvantages of the major models
      commonly accepted and used, in such a form that the reader who may not be an
      expert in the field would be led either to a choice of a particular model for a
      specific purpose or to appreciate a paper or a report based on an experimental
      model of arterial thrombosis. In vitro models of arterial thrombosis are so far
      removed from reality and due to their nature can generate so much artifacts that
      we have omitted their discussion from this paper.

PMID- 8979113
TI  - Modulating platelet function with selective thrombin inhibitors.
AB  - In addition to its pivotal role in blood coagulation, thrombin is one of the most
      important agonists for platelet recruitment and aggregation. Thrombin inhibitors
      impede thrombin-induced platelet aggregation but have no effect on aggregation
      induced by other agonists. A review is presented of selective thrombin inhibitors
      now in clinical investigation, some of which are also orally active.

PMID- 8979114
TI  - New thoughts on strategies for modulating platelet function through the
      inhibition of surface receptors.
AB  - Platelets play a key role in arterial thrombosis. Inhibition of platelet function
      forms an essential part of anti-thrombotic therapy. Although aspirin is a cost
      effective drug which offers considerable scope in the prevention of arterial
      thrombosis, it only inhibits part of the platelet activation process. Much recent
      progress has concerned the inhibition of surface receptors of platelets.
      Ticlopidine and clopidogrel specifically interfere with the ADP-induced
      activation pathway. Inhibitors of GP IIb-IIIa complexes, including c7E3, block
      the final step of the platelet aggregation process as used by all physiologic
      agonists and are proving powerful therapeutic agents. This review looks at these
      and future advances in the construction of therapeutic strategies aimed at
      combatting arterial thrombosis.

PMID- 8979116
TI  - Analysis of the kinetics of factor X activation by tissue factor-factor VIIA.
AB  - In this paper we consider the assumptions that apply to the classical Michaelis
      Menten enzyme kinetics and examine their applicability to a two-dimensional
      catalytic system. While we specifically address the kinetics of factor X
      activation catalyzed by a complex of tissue factor and factor VIIa, these
      concepts are applicable to any system in which both enzyme and substrate are
      membrane-bound. We emphasize the fact that the membranes become crowded with
      substrate and product molecules, thus rendering the assumption of "sparseness"
      inappropriate. Data from computer simulations are considered as well as
      preliminary laboratory experiments.

PMID- 8979115
TI  - Tissue factor pathway inhibitor: regulation of its inhibitory activity by
      phospholipid surfaces.
AB  - The basic C-terminus of Tissue Factor Pathway Inhibitor (TFPI) appears to be
      essential for its anticoagulant activity when tested in a diluted thromboplastin
      prothrombin time assay. Although the data reported so far have increased our
      knowledge about the C-terminus as a major binding site for heparin, lipoproteins
      and phospholipids, it is still unclear how this region of TFPI plays a role in
      its anticoagulant mode of action. We earlier reported that in the presence of
      phospholipid the rate of association of factor Xa with full length TFPI (FL-TFPI)
      is about 10-fold faster than with C-terminus truncated TFPI. This in turn makes
      that, in vitro, full length TFPI is a more potent inhibitor of tissue factor
      factor VIIa catalyzed factor X activation than truncated TFPI. Binding studies,
      utilizing an ellipsometer, revealed that in contrast to the complex of C-terminus
      truncated TFPI (TFPI1-161) and factor Xa, the FL-TFPI.factor Xa complex has a
      high affinity for negatively charged phospholipids. However, when examined in a
      tubular flow reactor containing tissue factor embedded in a phospholipid bilayer
      composed of 25 mol% phosphatidyl-serine/75 mol% phosphatidylcholine, no
      differences in the potency of FL-TFPI and TFPI1-161 to inhibit factor X
      activation were found. The two variants of TFPI did show an interesting
      difference though. We found that the quaternary complex of TF.factor VIIa.FL
      TFPI.factor Xa was much more stable than the complex containing TFPI1-161. This
      difference could not be attributed to their different phospholipid-binding
      properties since the same difference in stability was found on membranes that
      contained only DOPC.

PMID- 8979117
TI  - Platelet activation: new aspects.
AB  - Work on growth factor receptors in other cells has led to the concept that
      tyrosine phosphorylation of receptor cytoplasmic domains leads to recruitment of
      signaling molecules to appropriate sub-membrane locations. Complexes of molecules
      are assembled through structural motifs that mediate phosphotyrosine-SH2 domain
      and SH3-proline-rich domain interactions. These interactions lead to activation
      of signaling molecules, especially activation of members of the Ras superfamily
      that in turn mediate downstream effects on gene regulation, vesicle movement, and
      cytoskeletal reorganizations. In platelets, signaling occurs primarily through
      members of the seven transmembrane-hererotrimeric G-protein coupled family of
      receptors and through adhesion receptors. The most rapid are of growth in recent
      years has been the realization that signaling through both G-protein coupled
      receptors and adhesion receptors is dependent on tyrosine kinase activation,
      recruitment of complexes of SH2, SH3, and proline-rich signaling molecules to
      appropriate locations in the cell, and on activation of members of the Ras
      superfamily of proteins. Because neither G-protein coupled receptors nor adhesion
      receptors have intrinsic tyrosine kinase activity, mechanisms presumably exist
      for using non-receptor kinases to initiate tyrosine phosphorylation reactions
      that in turn lead to the recruitment of signaling molecules. As discussed in this
      article, many tyrosine kinases exist in platelets and some of these are known to
      be tyrosine phosphorylated and activated following platelet activation. The theme
      that is emerging is that these tyrosine kinases may serve to phosphorylate
      submembranous proteins including receptors for cytoplasmic domains or components
      of the submembranous cytoskeleton of adhesion-receptor cytoskeleton complexes
      that can then recruit and activate appropriate signaling molecules. The challenge
      in future years will be to identity the way in which the activation of tyrosine
      kinase(s) is induced by receptor activation, identify the tyrosine kinase(s)
      involved, and identify the way in which specific members of the Ras superfamily
      activate downstream effectors to induce the responses of platelets to activation.

PMID- 8979118
TI  - Genetic analysis of the plasminogen and coagulation system in mice.
AB  - The blood coagulation and the fibrinolytic (or plasminogen/plasmin) systems
      determine the balance between the formation and dissolution of blood clots, but
      in addition contribute to the pathogenesis of various cardiovascular disorders
      such as thrombosis, atherosclerosis and restenosis. Furthermore, they participate
      in a variety of other (patho)biological processes such as embryonic development,
      reproduction, wound healing, cancer and brain function. Two recently developed
      technologies, gene targeting and gene transfer, that allow to manipulate the
      genetic balance of these proteinase systems in a controllable manner have allowed
      to more definitively elucidate the biological role of these systems. This review
      summarizes the insights that have been obtained from the gene targeting studies
      and discusses the use of adenovirus-mediated transfer of fibrinolytic genes to
      study and possibly to develop novel strategies for the treatment of restenosis
      and thrombosis.

PMID- 8979119
TI  - Tissue factor pathway inhibitor (TFPI)--an update.
AB  - There is compelling experimental evidence that tissue factor pathway inhibitor
      (TFPI) exerts important role(s) as a natural anticoagulant. Immunodepletion of
      TFPI lowers the treshold by which tissue factor (TF) can induce disseminated
      intravascular coagulation. Conversely, infusion of recombinant TFPI protects
      against thrombosis and disseminated intravascular coagulation in numerous
      experimental models. Since TFPI mutants associated with thrombosis have not yet
      been identified, a definite role of TFPI in coagulation is yet to be assigned.
      Current research on TFPI is mainly focused on the cell biology of TFPI, on the
      contribution of TFPI to the anticoagulant action of heparins, and on the role of
      lipoprotein-associated TFPI. TFPI is produced constitutively in endothelial
      cells, and is to a great extent bound to its surface. The binding molecule(s)
      have not yet been characterized, but TFPI is rapidly released by heparin and
      other negatively charged ions. In other cell lines degradation of TFPI is
      mediated by the low density lipoprotein receptor-related protein, which may be
      important for its clearance. In plasma, TFPI contributes strongly to the
      postheparin anticoagulant effect seen in dilute prothrombin time assays. The
      effect is probably mediated by redistribution of TFPI. Moreover, in the presence
      of heparin, antithrombin and TFPI cooperate to inhibit activation of coagulation.
      Antithrombin abrogates activation of factor VII bound to TF, whereas TFPI
      inhibits factor VIIa/TF complexes formed. The role of lipoprotein associated TFPI
      is still essentially unknown, but may play an important role in atherosclerosis.

PMID- 8979120
TI  - Hemorheological profile in patients with cardiovascular risk factors.
AB  - In order to find out whether hemorheological alterations precede the
      atherosclerotic lesions and could constitute an atherothrombotic risk factor, we
      studied the hemorheological profile in 150 healthy normotensive offspring whose
      parents were diagnosed as having essential hypertension WHO I-II grade and in
      another group of 40 children with familial hypercholesterolemia (FH) but without
      vascular atherosclerosis lesions, whose parents also suffer from FH. In offspring
      of hypertensive individuals, a significant increase in the fibrinogen level with
      respect to the control group was found both in males and females. In addition,
      only the female offspring showed a higher leucocyte count. FH children showed
      increased erythrocyte aggregation and increased plasma viscosity with respect to
      the control group. The fact that the rheological alterations appear prior to the
      development of the vascular lesion suggests that they could play a role in the
      pathogenesis of the atherosclerotic process.

PMID- 8979122
TI  - Influence of hypoxia and hypoxia-reoxygenation on endothelial P-selectin
      expression.
AB  - P-selectin is an endothelial adhesion molecule involved in the initial step of
      the neutrophil recruitment. We investigated the effect of hypoxia (95% N2, 5%
      CO2) and of hypoxia-reoxygenation (95% air, 5% CO2) on the expression of P
      selectin by human umbilical vein endothelial cells (HUVEC). P-selectin expression
      was detected by immunolabelling and quantified by flow cytometric analysis. Our
      data indicate that hypoxia induces an increase in P-selectin expression with a
      maximum reached after 90 minutes. A hypoxic exposure of 90 minutes results in a
      highly significant increase compared to normoxia (p < 0.001, n = 13).
      Furthermore, when a reoxygenation period follows 90 minutes of hypoxia, the
      initially elevated levels of P-selectin are dramatically enhanced with a maximum
      obtained after 60 minutes of reoxygenation.

PMID- 8979121
TI  - Effect of HMG-CoA reductase inhibitors on red blood cell membrane lipids and
      haemorheological parameters, in patients affected by familial
      hypercholesterolemia.
AB  - Eighteen patients with familial hypercholesterolemia treated with lovastatin (40
      mg/day) for three months were studied to find out whether the drug induces
      modifications in the lipid composition of the erythrocyte membrane and whether
      these induce changes in the rheological behaviour of the red blood cell. Our
      results show that the changes observed in plasma lipids correlate with a
      significant decrease in the cholesterol/phospholipid ratio of the red blood cell
      membrane. These changes in the lipid composition of the cell are statistically
      related to a decrease in the erythrocyte aggregability and an improvement in
      blood filterability probably due to an increase in the red blood cell
      deformability.

PMID- 8979123
TI  - Effect of buflomedil on the neutrophil-endothelial cell interaction under
      inflammatory and hypoxia conditions.
AB  - In hypoxia/ischaemia and ischaemia/reperfusion, human neutrophils are likely to
      play an important role in the development of endothelial cell damage in the
      microcirculation. Buflomedil hypochloride improves the capillary perfusion in
      such related situations, evoking a possible effect upon neutrophils. Using in
      vitro models of cell adhesion, buflomedil decreased 100% of histamine related
      neutrophil adhesion (flow system) and partially inhibited adhesion after IL-1-4
      hours (flow and stable systems). Hypoxia induced neutrophil adhesion (4 hours)
      was also reduced by buflomedil, which decreased the expression of P-selectin at
      the surface of endothelial cells. As adenosine (NECA) exhibited the same results
      in hypoxia and theophylline inhibited them, such results support an action of
      buflomedil presumably via the A2 receptor.

PMID- 8979124
TI  - Comparison of the relative efficacy and safety of low molecular weight heparin
      and unfractionated heparin for the treatment of venous thrombosis.
AB  - LMWH has been compared with unfractionated heparin in the treatment of venous
      thrombosis. The results of a pooled analysis studies of hospitalized patients
      showed a significant reduction of thrombus size, p < 0.001 and in the incidence
      of recurrent venous thromboembolism, p < 0.001 and of major bleeding p < 0.005 in
      patients treated with LMWH. The pooled mortality rate at long term follow-up was
      also found to be lower in LMWH group. Two large randomized trials have been
      completed in which LMWH was administered subcutaneously on an outpatient basis
      and compared with the standard approach of unfractionated heparin administered by
      continuous intravenous infusion in hospital. In both studies the efficacy, safety
      and mortality in the LMWH and heparin groups were similar.

PMID- 8979125
TI  - Platelet activation via trimeric GTP-binding proteins.

PMID- 8979126
TI  - Adhesive proteins at endothelial cell-to-cell junctions and leukocyte
      extravasation.
AB  - Endothelial cell junctions are complex structures formed by transmembrane
      adhesive molecules linked to a network of cytoplasmic/cytoskeletal proteins. At
      least four different types of endothelial junctions have been described (tight
      junctions, gap junctions, adherence junctions and syndesmos or complexus
      adhaerentes). Leukocytes adhesion to endothelial cells is frequently followed by
      their extravasation. The mechanisms which regulate the passage of leukocytes
      through endothelial clefts remain to be clarified. Many indirect data suggest
      that leukocytes might transfer signals to endothelial cells both through the
      release of active agents and adhesion to the endothelial cell surface. These
      signals could induce the disorganization of interendothelial junctions and
      facilitate leukocyte transmigration.

PMID- 8979127
TI  - Management of venous thromboembolism: optimization by clinical trials.
AB  - Antithrombotic therapy is mandatory in most patients with venous thrombosis. The
      results of randomized trials have established the requirement for initial
      treatment with heparin and have determined the optimal anticoagulant regimen for
      secondary prophylaxis. Recent studies have demonstrated that low molecular weight
      heparins, that have improved pharmacologic and pharmacokinetic properties over
      standard heparin, are effective and safe in the treatment of deep vein
      thrombosis. Two large randomized clinical trials have shown the feasibility of
      the outpatient treatment of patients with acute deep vein thrombosis with low
      molecular weight heparins. Home therapy will result in improved clinical utility
      of anticoagulant treatment and in cost savings.

PMID- 8979128
TI  - Directed search for thrombomodulin gene mutations.
AB  - Thrombomodulin is a principle thrombin receptor located on the vascular
      endothelium. Thrombomodulin alters the specificity of thrombin, redirecting its
      procoagulant function to an anticoagulant function by making it a more efficient
      activator of protein C. While mutation of the genes of other components of this
      anticoagulant mechanism, protein C, protein S and factor V, is known to
      predispose towards venous thromboembolism, there are only a few reports of the
      investigation of thrombomodulin gene mutation. We present the design and
      evaluation of a strategy to investigate thrombomodulin gene mutation in arterial
      and venous thrombosis.

PMID- 8979129
TI  - Considering cellular thrombomodulin distribution and its modulating factors can
      facilitate the use of plasma thrombomodulin as a reliable endothelial marker?

PMID- 8979130
TI  - Hemostasis during pregnancy and puerperium.

PMID- 8979131
TI  - Precision and accuracy of the international normalized ratio in oral
      anticoagulant control.
AB  - Precision is defined as the agreement between replicate analyses of the same
      material. Within-laboratory precision of the prothrombin time (PT) and INR can be
      optimized by choosing an appropriate combination of thromboplastin and
      instrument. Accuracy (true value) of the International Sensitivity Index (ISI),
      required for the calculation of INR, depends on the choice of international
      reference preparation for the thromboplastin, and on the instrument used by the
      local laboratory. Interaction between thromboplastin and each patient's
      individual coagulation factors influences the accuracy of the INR. The
      contributions of imprecision, inaccuracy, and interaction effects can be combined
      to calculate the total uncertainty of the INR using Tomenson's equation.
      Confidence intervals for the INR were calculated in typical examples. The 95%
      confidence intervals of the INR around 3 are approximately as wide as currently
      recommended therapeutic target ranges.

PMID- 8979132
TI  - European concerted action on anticoagulation (ECAA).

PMID- 8979133
TI  - Plaque rupture, thrombosis, and therapeutic implications.
AB  - The basic mechanisms of atherosclerotic progression leading to the acute coronary
      syndromes (ACS) have been elucidated during the last few years. In this brief
      presentation, we outline 1) Definition of Atherosclerotic Lesions: eight
      morphologically different lesions are defined (Type I to VI) in various phases of
      disease. 2) Vulnerable Lipid-Rich Plaques and the ACS: The type IV and Va lesions
      tend to be relatively small in size, but soft or vulnerable to a "passive"
      phenomenon of plaque disruption; in addition, an "active" macrophage-dependent
      enzymatic (genesis of metalloproteinase) phenomenon of plaque disruption is
      evolving. 3) Thrombosis: we have shown that monocytes/macrophages in lipid-rich
      plaques may play a detrimental role after plaque disruption, promoting thrombin
      generation and thrombosis through the tissue factor pathway that can be prevented
      by tissue factor pathway inhibition; such pathway of thrombosis appears to be
      critical in the development of the ACS. 4) Effect of Lipid-Modifying Strategies
      and other Risk Factors on the Vulnerable Lipid-Rich Plaques: when high LDL
      cholesterol is reduced therapeutically, efflux from the plaques of the liquid or
      sterified cholesterol, and also its hydrolysis into cholesterol crystals
      depositing in the vessel wall, predominate over the influx of LDL-cholesterol;
      consequently, there is a decrease in the softness of the plaque and so,
      presumably in the "passive" phenomenon of plaque disruption; modification of
      other risk factors presumably also favorably affect LDL-cholesterol influx and
      efflux. 5) Antithrombotic Strategies: the evolving antithrombotic approaches
      under investigation are briefly outlined.

PMID- 8979135
TI  - Fibrin-selective thrombolytic therapy with recombinant staphylokinase.

PMID- 8979134
TI  - The anti-GPIIb-IIIa agents: fundamental and clinical aspects.
AB  - The platelet GPIIb/IIIa receptor mediates platelet aggregation induced by all
      physiologic agonists. Blockade of the receptor, either by monoclonal antibodies
      or small molecules patterned after the arginine glycine-aspartic acid (RGD) cell
      recognition domain, prevents arterial thrombosis in animal models much better
      than does aspirin. c7E3 Fab, the Fab fragment of the mouse/human chimeric
      antibody 7E3 (abciximab: ReoPro), was shown to reduce ischemic events after
      angioplasty when given in conjunction with heparin and aspirin to patients at
      high risk in the EPIC study, but its was associated with an increase in bleeding.
      Preliminary data from the subsequent EPILOG study, in which a lower dose of
      heparin was used, demonstrated efficacy in low risk as well as high risk patients
      and no significant increase in major bleeding. Preliminary data from the CAPTURE
      study support the use of c7E3 Fab in patients with unstable angina who are
      candidates for PTCA within 24 hours. Positive trends toward decreased thrombotic
      events have also been observed in patients treated with small molecule inhibitors
      of GPIIb/IIIa receptors. This new class of agents thus holds promise for
      improving the therapy of angioplasty as well as perhaps other thrombotic
      phenomena.

PMID- 8979136
TI  - Inherited resistance to activated protein C caused by presence of the FV:Q506
      allele as a basis of venous thrombosis.
AB  - Inherited resistance to activated protein C (APC) was recently discovered as a
      cause of familial thrombophilia and is now known to be the most common genetic
      risk factor for venous thrombosis. In a majority of cases, APC resistance is
      associated with a single point mutation in the factor V gene, which results in
      substitution of arginine (R) at position 506 by glutamine (Q) (FV:Q506). The
      mutation renders factor Va partially resistant to degradation by activated
      protein C (APC), which leads to a hypercoagulable state and a life-long 5-10-fold
      increased risk of venous thrombosis. The previously known inherited deficiencies
      of antithrombin, protein S or protein C, are in western societies together found
      in less than 10-15% of thrombosis patients, whereas APC resistance is present in
      20 to 60% of the patients. A functional APC resistance test, which includes
      predilution of the patient plasma with factor V deficient plasma, is 100%
      sensitive and specific for the presence of FV:Q506. The FV:Q506 allele is common
      in populations of Caucasian origin (prevalence ranging between 1 and 15%),
      whereas it is not found in certain other ethnic groups such as in Japanese and
      Chinese. The thrombotic risk in individuals with APC resistant may be further
      increased by other genetic defects such as protein C or protein S deficiency and
      by exposure to circumstantial risk factors such as oral contraceptives,
      pregnancy, immobilisation and surgery.

PMID- 8979137
TI  - Diagnosis and clinical characteristics of inherited activated protein C
      resistance.
AB  - The diagnostic strategies and clinical characteristics of thrombophilia
      associated with heterozygous or homozygous factor V Leiden mutation have been
      determined according to the literature and to a personal study in 51 families.
      Factor V mutation was present in the 51 propositi and in 84 out of 125 family
      members (81 heterozygous, 3 homozygous). Venous thrombosis was observed in all
      the propositi, in 17 of the 84 family members with the mutation and in 6 of the
      41 with a normal APC resistance test and no mutation. An associated protein C or
      protein S deficiency was present in 5 families (10%). The most frequent clinical
      manifestations were superficial or deep vein thrombosis and/or pulmonary
      embolism, but also thrombosis at an unusual site (cerebral, mesenteric or central
      retinal vein). A causal relationship is frequently difficult to demonstrate. A
      precipitating factor was observed in 84% of cases and a recurrent thrombotic
      episode occurred in 50% of propositi. The risk of thrombosis associated with
      pregnancy was high in the post-partum period, especially in homozygous women. In
      the 28 homozygous subjects, markers of coagulation activation were frequently
      elevated in untreated patients. Finally, the efficacy of anticoagulant treatment
      is suggested but the long period often observed between treatment interruption
      and a recurrence does not militate in favour of long term treatment.

PMID- 8979138
TI  - Regulation of fibrinogen biosynthesis by cytokines, consequences on the vascular
      risk.
AB  - High level of fibrinogen in plasma is recognised as an important vascular risk
      factor. However, it is not known if the increase in fibrinogen is directly
      responsible for the vascular risk or is a marker of vascular inflammation. Our
      data strengthen the hypothesis that the fibrinogen level is a marker of vascular
      disease, since a parallel effect of cytokines on fibrinogen biosynthesis and on
      vascular injury was noted. Among the cytokines which induce the synthesis of
      fibrinogen, oncostatin M (OSM) is the most potent cytokine synthesised by
      activated monocytes for inducing fibrinogen synthesis by Hep G2 cells (human
      hepatoma cell line). Interestingly at the same concentrations needed for
      fibrinogen biosynthesis, OSM induces smooth muscle cell proliferation. In
      contrast, the cytokines IL-4, IL-10 and IL-13 which have a protective effect
      against vascular injury leading to atherosclerosis, dose dependently down
      regulate the biosynthesis of fibrinogen. This was due to both a decrease of IL-6
      induced fibrinogen synthesis by hepatocytes, evidenced by a decrease in
      fibrinogen secretion in the medium and beta chain mRNA expression and to an
      inhibition of production of the hepatocyte-stimulating activity for fibrinogen
      biosynthesis (HSF) by LPS-activated monocytes. Noteworthingly, IL-10 induces a
      significant decrease of the production of OSM by LPS-activated monocytes. In situ
      activation of monocytes by cytokines in the vessel wall could also contribute to
      the deposition of fibrin(ogen) derivatives, identified as pathogenic factor.

PMID- 8979139
TI  - Pathogenic role of antiprotein-phospholipid antibodies.
AB  - Antiphospholipid antibodies (aPL) are a heterogeneous family of antibodies,
      including those specific for a variety of phospholipid (PL)-binding proteins and
      also those reacting with PL molecules. The former seem to be associated with the
      antiphospholipid syndrome (APS). At present, the main proteins proposed as
      antigens are beta 2 glycoprotein I, prothrombin, protein C, protein S, kininogens
      and annexin V. Anionic PL might play a key role "in vivo" in the binding of aPL
      to PL-bound proteins. Different mechanisms may be involved in the pathogenesis of
      the APS, including effects of aPL on the protein C system and antithrombin III
      and also on platelets, endothelial cells and monocytes. Recent data on
      experimental animal models have provided support for a causative role of aPL in
      the clinical complications of the APS.

PMID- 8979141
TI  - New antithrombotic agents for the prevention and treatment of deep vein
      thrombosis.
AB  - Besides low molecular weight heparins (LMWHs) a number of new antithrombotic
      agents have been evaluated mainly in the prevention of deep vein thrombosis (DVT)
      and, to a lesser extent, in the treatment of established DVT. They include the
      Pentasaccharide, a synthetic ultra LMWH, Dermatan Sulphate, a glycosaminoglycan
      which activates heparin cofactor II, Orgaran, a mixture of Heparan and of
      Dermatan Sulphate, Hirulog and Hirudin, two direct thrombin inhibitors. The
      efficacy and safety of these compounds have been studied in comparison with a
      placebo or with unfractionated heparin but not with LMWH which is considered as a
      gold standard for these clinical indications. It is thus difficult at present to
      appreciate the advantages of these new antithrombotic agents over conventional
      LMWH therapy.

PMID- 8979140
TI  - Antiphospholipid-protein antibodies: clinical use of laboratory test results
      (identification, predictive value, treatment).
AB  - Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which
      recognize protein-phospholipid complexes. Among the proteins implicated are: beta
      2 Glycoprotein I, prothrombin, Annexin V, protein C, and protein S. Laboratory
      tests are used to identify, predict potential clinical complications, and manage
      patients with the antiphospholipid-protein syndrome (APS). Emerging evidence
      suggests laboratory tests can be used to stratify relative risk of patients with
      APA.

PMID- 8979142
TI  - Prolonged prophylaxis against postoperative venous thromboembolism.
AB  - This review deals with the problem of delayed thrombosis and thereby the
      potential need of prolonged prophylaxis. The risk of late thrombosis and
      pulmonary embolism is discussed from pathogenetic factors and data on frequencies
      of thromboembolic complications in the literature. The problems concerning long
      term or prolonged prophylaxis are indicated and studies on prolonged prophylaxis
      our own included-are analyzed. There is an urgent need to define which risk
      factors motivate prolonging thromboprophylaxis for more than the standard 7-14
      days.

PMID- 8979143
TI  - A mathematical model of coagulation factor VIII kinetics.
AB  - It appears that the binding of coagulation factor VIII to von Willebrand factor
      in plasma stabilizes the otherwise highly labile factor VIII. A mathematical
      model of factor VIII kinetics has been developed based upon this proposed effect
      of factor VIII binding. The model's kinetic parameter values have been estimated
      by fitting the model to data available in the medical literature. The model gives
      accurate quantitative predictions of the elevated steady-state concentrations of
      factor VIII in clinical conditions associated with the acute phase reaction and
      in pregnancy, the decreased steady-state concentrations of factor VIII in females
      heterozygous for hemophilia, the decreased steady-state concentrations of factor
      VIII in patients with type 1 (heterozygous) and type 3 (homozygous) von
      Willebrand disease, and the variable half-life of factor VIII in factor
      replacement therapy for hemophilia and von Willebrand disease.

PMID- 8979146
TI  - Acquired factor VIII inhibitor in a patient with tuberculosis.

PMID- 8979144
TI  - Coagulopathy of childhood nephrotic syndrome--a reappraisal of the role of
      natural anticoagulants and fibrinolysis.
AB  - In an attempt to characterise further the coagulopathy of childhood nephrotic
      syndrome, this study concentrates on simultaneous measurements of the natural
      anticoagulants [antithrombin III (ATIII), proteins C and S] and the fibrinolytic
      factors, tissue plasminogen activator (tPA) and plasminogen activator inhibitor
      (PAI). The study groups consisted of 41 children (ages ranging from 2 to 14
      years; median 7.1) in the relapse of nephrosis and 48 children (ages ranging from
      3 to 14 years; median 7.6) in remission. The results obtained were compared with
      normal values obtained in healthy age- and sex-matched controls (n = 103). During
      relapse, there was a marked increase in the plasma level of fibrinogen, protein
      C, and protein S and reduced plasma ATIII level; tPA level was similar to control
      but PAI level exhibited a significant reduction. During remission, the protein C
      level either remained elevated or increased further, but some decreased. Protein
      S and plasma ATIII level normalised. The fibrinolytic activator tPA dropped
      slightly but the PAI level remained significantly below control levels. We
      conclude that in the relapse of childhood nephrosis, despite the existence of a
      significant prothrombotic tendency as featured by hyperfibrinogenaemia and
      markedly reduced ATIII level, the simultaneous elevation of the natural
      anticoagulant, protein C level and enhanced fibrinolysis that persist until the
      remission phase, seem to be major preventive mechanisms guarding nephrotic
      children against thromboembolic phenomena.

PMID- 8979145
TI  - Prostanoid production in the presence of platelet activation in hypoxic cocaine
      treated rats.
AB  - To extend our previous in vitro data, we investigated the effects of cocaine on
      thromboxane A2 (TXA2) and prostacyclin (PGI2) production in vivo in the rat. To
      obtain the slight platelet activation that our in vitro experiments showed useful
      to highlight the effect of cocaine, we infused cocaine in rats in the presence of
      platelet-activating factors (circulation of blood through a perspex vascular
      device or by infusion of sodium arachidonate) and in various respiratory
      conditions. Experiments were conducted in rats breathing atmospheric air
      (normoxic conditions) and in rats breathing an oxygen-poor mixture (hypoxic
      conditions). In rats under hypoxic conditions cocaine invariably increased TXA2
      plasma levels, whereas in normoxic conditions it increased TXA2 only in the
      presence of platelet-activating factors. Cocaine significantly increased PGI2
      plasma levels in arachidonate-treated rats in hypoxic respiratory conditions; in
      normoxic conditions cocaine left PGI2 levels unchanged. These results support the
      hypothesis that in cocaine users who have concomitant pathological conditions
      able to activate platelets, such as atherosclerosis, coronary vasospasm or
      ischaemia, or both, cocaine may contribute to the onset of thrombotic phenomena
      by interfering with the prostaglandin system.

PMID- 8979147
TI  - Reagent dependency of derived fibrinogen method.

PMID- 8979148
TI  - Estriol: a potent regulator of TNF and IL-6 expression in a murine model of
      endotoxemia.
AB  - The increased incidence of autoimmune disease in premenopausal women suggests the
      involvement of sex steroids in the pathogenesis of these disease processes. The
      effects of estrogen on autoimmunity and inflammation may involve changes in the
      secretion of inflammatory mediators by mononuclear phagocytes. Estradiol, for
      example, has been reported to regulate TNF, IL-6, IL-1 and JE expression. In the
      present study the effects of the estrogen agonist, estriol, on cytokine
      expression have been investigated in mice administered a sublethal
      lipopolysaccharide, LPS, challenge. Pretreatment of mice with pharmacologic doses
      of estriol, 0.4-2 mg/kg, resulted in a significant increase in serum TNF levels
      in both control and autoimmune MRL/lpr mice, following LPS challenge. This
      increase in TNF over the placebo group was blocked by the estrogen antagonist
      tamoxifen. Estriol treated mice also exhibited a rapid elevation in serum IL-6
      levels following LPS challenge with the peak increase occurring 1 hr post LPS.
      This contrasted with the placebo group in which maximal serum IL-6 levels were
      detected at 3 hrs post challenge. This shift in the kinetics of IL-6 increase by
      estriol was inhibited by tamoxifen. The estriol mediated effects of TNF and IL-6
      serum levels were consistent with the changes in TNF and IL-6 mRNA observed ex
      vivo in elicited peritoneal macrophages. Macrophage cultures from estriol treated
      animals however, did not demonstrate significant differences from the placebo
      group for TNF or NO secretion following in vitro LPS challenge. These results
      suggest that the estrogen agonist estriol can have significant quantitative, TNF,
      and kinetic, IL-6, effects on inflammatory monokines produced in response to an
      endotoxin challenge.

PMID- 8979149
TI  - Zinc (Zn2+) binds to and stimulates the activity of group I but not group II
      phospholipase A2.
AB  - Phospholipase A2 plays an important part in the generation of inflammatory lipid
      mediators and so it is of major interest to understand functional distinctions
      between structurally similar forms of phospholipase A2. In the present study, the
      influence of zinc (Zn2+) on the activity of group I and group II phospholipase A2
      was examined in vitro. It appeared that Zn2+ (0.04-1 x 10(-3)M) increased group I
      phospholipase A2 activity from porcine pancreas and rat lung whereas the activity
      of group II phospholipase A2 from Crotalus atrox and Vipera russelli was
      unaffected. The presence of Cd2+ of Hg2+ (0.8-5 x 10(-3)M) also increased group I
      pancreatic phospholipase A2 activity while no augmentation was found with Cr2+,
      Fe2+ or Mg2+. The selective stimulation of group I phospholipase A2 by Zn2+
      corresponded to a binding of these phospholipases A2 to a zinc-affinity column,
      while group II phospholipase A2 was not bound. Furthermore, the PLA2 activity in
      bronchoalveolar lavage fluid from rat was stimulated by Zn2+. These results
      indicate that Zn2+ binds to and increases the activity of group I, but not group
      II phospholipase A2. This difference in Zn(2+)-binding may be used to
      discriminate between group I and group II phospholipase A2 and to separate the
      enzymes from each other in complex biological materials. The possibility that
      activation of group I phospholipase A2 in the lung is important in zinc-induced
      metal fume fever is implied.

PMID- 8979151
TI  - Assessment of the antiexudative and antiproliferative activities of non-steroidal
      anti-inflammatory drugs in inflammatory models developed in rats by subcutaneous
      implantation of bacterial cell walls from the dental plaque.
AB  - A purified bacterial cell walls suspension from human dental plaque were
      biochemically prepared to serve as flogogenous agent in producing experimental
      inflammatory models in rats. In the vascular permeability inhibition assay
      (edemogenic test), the subcutaneous implantation of the flogogenous agent
      elicited an acute inflammatory reaction highly susceptible to the effects of the
      non-steroidal anti-inflammatory drugs (NSAIDs). The intradermal injection of the
      flogogenous agent in the dorsum of rats developed experimental granulomas also
      susceptible to the anti-inflammatory effects of the NSAIDs. Otherwise, the
      antimitotic effect of drugs was carried out in the model of cellular
      proliferation of duodenal mucosa of rats by incorporation of tritiated thymidine
      (3H TdR) in the DNA. These models of acute and chronic inflammation, and the
      antimitotic model permitted us to evaluate the anti-inflammatory and antimitotic
      effects of sulindac, ibuprofen, naproxen and glucametacin. In the antiexudative
      activity, evaluated by the edemogenic test, naproxen was the more effective drug
      followed by sulindac, ibuprofen and glucametacin (in a decreasing order of
      potency) to inhibit the exudative response induced by the bacterial cell walls
      suspension, in all experimental periods. In the chronic anti-inflammatory
      activity, evaluated by the granuloma inhibition assay, all drugs were capable to
      demonstrate effectiveness against the development of the experimental granulomas
      induced by an intradermal injection of the flogogenous agent. In the model of
      cellular proliferation, all tested drugs demonstrated antimitotic activity in all
      experimental periods (4, 6 and 8 days), also. Sulindac induced the higher
      antimitotic effect, in all experimental periods, followed by ibuprofen, naproxen
      and glucametacin in a decreasing order of efficacy. There was a positive
      correlation between the antiexudative, anti-proliferative, and antimitotic
      effects.

PMID- 8979150
TI  - Kinetic evaluation of nitric oxide production in pleural exudate after induction
      of two inflammatory reactions in the rat.
AB  - NO generation in the course of two acute, non immune, inflammatory reactions
      (pleurisy induced by rat isologous serum and carrageenan) was assessed by means
      of nitrite measurement in pleural exudate from 0.5 to 24 h. NO release varied
      time-dependently, similarly for the two inflammatory reactions. A first, but
      transient, peak was reached in 30 min while a second peak, more sustained, began
      at the fourth hour and was maximum at the tenth. Kinetic evolution of NO release
      was consistent with activation, in a first step, of a constitutive NO synthase
      probably from endothelial origin (inhibited by 2-Methyl-2-Thiopseudourea sulfate
      but not by dexamethasone) and with activation, in a second wave, of inducible NOS
      from endothelial and exudative cells. NO release was potentiated by
      administration per os of L-Arginine and seems to be involved in the evolution of
      acute inflammatory reactions and oxygen metabolite production.

PMID- 8979152
TI  - Inhibition of rat pleural mesothelial cell nitric oxide synthesis by transforming
      growth factor-beta 1.
AB  - Pleuritis is a common initial clinical manifestation of tuberculosis. It is
      associated with an accumulation of a variety of cytokines in the pleura and
      pleural fluid. We have recently shown that these proinflammatory cytokines induce
      the pleural mesothelial cell to produce large amounts of nitric oxide, a nitrogen
      intermediate that has been shown to have a tuberculocidal effect. TGF-beta has
      also been found in situ in tuberculous effusions and pleural tissues and is
      thought to suppress the immune response and promote tissue repair. This study
      examined the effects of TGF-beta on cytokine-induced NO synthesis by rat pleural
      mesothelial cells in vitro. Results demonstrated that TGF-beta significantly
      inhibited NO synthesis and that this inhibition was associated with a
      proportionate decrease in iNOS mRNA and iNOS protein. Suppression of pleural
      mesothelial cell NO synthesis by TGF-beta may be important in the pathogenesis of
      tuberculous pleuritis.

PMID- 8979153
TI  - Natural killer and lectin-dependent cytotoxic activities of Kurloff cells: target
      cell selectivity, conjugate formation, and Ca++ dependency.
AB  - Kurloff cells may represent a major component of NK cell activity in the guinea
      pig. We have pursued to characterize the mechanism of their action. Using murine
      target cells, we found Kurloff cell cytotoxicity to be selective for the NK
      sensitive YAC-1 target cell, with minimal activity against the NK-resistant P815
      target cell. In the presence of PHA, but not ConA, cytotoxicity was markedly
      augmented against both YAC-1 and P815. While effector-target conjugate formation
      was observed with YAC-1 cells but not P815 cells in control cultures, it was
      augmented with both target cell types in cultures with PHA. Pretreatment alone
      with PHA was ineffective, however. NK cell activity of Kurloff cells was
      dependent on extracellular Ca++ and entry of Ca++ into the effector cells, as
      demonstrated by abrogation of cytotoxicity when extracellular Ca++ was chelated
      with EDTA or EGTA, or following treatment with the Ca++ channel blockers
      verapamil and diltiazem. Furthermore, inhibition of PKC by H7 resulted in
      significant reduction of Kurloff cell-mediated NK activity, while pretreatment of
      effector cells with the PKC activator TPA enhanced NK activity. Kurloff cells
      could also be stimulated to produce serine esterases by contact with target cells
      or treatment with phorbol ester and ionophore. Finally, a majority of Kurloff
      cells, identified by the monoclonal antibody 14D1, reacted with the human NK cell
      marker CD56. Taken together, these data suggest that Kurloff cells have NK-like
      characteristics and activity, with target cell selectivity, and that their lytic
      mechanisms involve influx of extracellular Ca++, PKC activation and serine
      esterase production.

PMID- 8979154
TI  - Neutrophil migration, oxidative metabolism, and adhesion in elderly and young
      subjects.
AB  - OBJECTIVE: To evaluate neutrophil functions in the elderly. METHODS: We
      investigated the PMN migration in vivo and PMN superoxide production and adhesion
      in response to a variety of compounds; PMN have been isolated both from blood and
      from a skin experimental exudate (obtained by Senn's skin window technique) of 25
      normal elderly and of 25 normal young control subjects. RESULTS: No difference
      was found in PMN migration in vivo (62.9 +/- 21.3 x 10(6) and 65.5 +/- 9.1 x
      10(6) PMN/cm2/24 hours in elderly and young subjects respectively), neither were
      different the adhesion under basal condition and after some stimuli and the
      superoxide production in basal condition and in response to STZ and PMA in two
      groups. In elderly subjects superoxide production, in response to fMLP, markedly
      resulted lower than in young controls both by circulating PMNs (3.6 +/- 2.7 and
      9.3 +/- 3.3 nMOLES O2-/10(6) PMN respectively, p < 0.0001) and by exudate PMNs
      (13.6 +/- 4.3 and 19.4 +/- 6 nMOLES O2-/10(6) PMNs respectively, p < 0.005).
      CONCLUSION: Many PMN functions in the elderly do not differ from young people,
      suggesting that the overall defense function of these cells is not affected by
      aging. The only parameter that we have found to be different between the two
      groups is the poor superoxide production after fMLP stimulus of PMNs. The
      stimulus- and function-specificity of this defect in PMNs from elderly subjects
      indicates the existence of a dysregulation of the signal transduction pathway
      distal to fMLP receptor and proximal to NADPH oxidase activation.

PMID- 8979157
TI  - beta-Carotene accumulation in mouse tissues and a protective role against lipid
      peroxidation.
AB  - Mice were supplemented with beta-carotene in beverage for 10 days. After the
      supplement, beta-carotene accumulated mainly in the liver and to some extent in
      the blood plasma, kidney and lung. The beta-carotene administration was
      associated with an increase in the amount of retinyl ester and retinol in the
      liver, but not in the amount of retinol in blood plasma. Lipid peroxidation in
      vivo was induced by the injection of carbon tetrachloride under the dorsal skin
      of mice. As an index of lipid peroxidation, thiobarbituric acid-reacting
      substances (TBARS) were assayed in urine and tissue homogenates. Urine and kidney
      TBARS were reduced by the supplementation of beta-carotene. The amounts of TBARS
      in kidney, liver and lung, decreased with increasing amounts of beta-carotene
      accumulated in these tissues, i.e. inverse correlations were obtained. These
      results indicate that beta-carotene can suppress lipid peroxidation in mouse
      tissue.

PMID- 8979155
TI  - Endogenous nitric oxide and prostaglandin E2 do not regulate the synthesis of
      each other in interleukin-1 beta-stimulated rat articular cartilage.
AB  - Increased levels of nitric oxide (NO) and prostaglandins (PG) are present in the
      synovial fluid from patients with rheumatoid arthritis and osteoarthritis.
      Interleukin-1 beta (IL-1) has been shown to induce the synthesis of both of these
      mediators. The present work was designed to study the interactions of NO and PGE2
      synthesis induced by IL-1 in rat articular cartilage. Incubation of intact
      cartilage with IL-1 resulted in different dose response curves for NO and PGE2
      synthesis. Two inhibitors of nitric oxide synthase N-monomethyl-L-arginine (L
      NMMA) and L-N-iminoethylornithine, (L-NIO), abolished the IL-1-induced nitrite
      production but failed to have any influence on the PGE2 synthesis. Exogenous NO,
      produced by two chemically different NO-releasing compounds (SIN-1 and GEA 3175)
      had no effect on PGE2 synthesis in articular cartilage. Dexamethasone and
      ketoprofen inhibited IL-1 induced PGE2 production, while nitrite synthesis
      remained unaltered. Acetylsalicylic acid (ASA) reduced PGE2 synthesis and had a
      slight inhibitory action also on NO production. In conclusion, our results show,
      that IL-1 induces the synthesis of both PGE2 and NO in articular cartilage but
      these two inflammatory mediators are not mediating the synthesis of one another.

PMID- 8979156
TI  - Membrane-stabilizing, anti-inflammatory interactions of macrolides with human
      neutrophils.
AB  - The effects of the macrolide antimicrobial agents azithromycin, clarithromycin,
      erythromycin and roxithromycin on the prooxidative activity of stimulated human
      neutrophils have been investigated in vitro. Superoxide generation by activated
      neutrophils was measured by lucigenin-enhanced chemiluminescence. At the
      concentrations used (2.5-80 micrograms/ml) none of the test agents was cytotoxic,
      nor did they possess superoxide-scavenging properties. Treatment of neutrophils
      with all 4 macrolides was accompanied by dose-related inhibition of superoxide
      production by cells activated with FMLP or the calcium ionophore (A23187), while
      the responses activated by phorbol myristate acetate (PMA) or opsonized zymosan
      were minimally affected. The anti-oxidative interactions of roxithromycin with
      FMLP-activated neutrophils were neutralized by pretreatment of the cells with
      low, non-cytotoxic concentrations (0.5 microgram/ml) of the prooxidative,
      proinflammatory bioactive phospholipids, lysophosphatidylcholine (LPC), platelet
      activating factor (PAF) and lyso-PAF (LPAF). Using an assay of membrane
      stabilizing activity, the macrolides antagonized the membrane-disruptive effects
      of LPC, PAF and LPAF, without affecting enzymes involved in their synthesis.
      These membrane-stabilizing interactions of macrolides with neutrophils may
      counteract the proinflammatory, prooxidative activity of several bioactive lipids
      which have been implicated in the pathogenesis of bronchial asthma.

PMID- 8979158
TI  - Modulation of ultraviolet light-induced oxidative stress in mice skin related to
      dietary vitamin A and selenium intake.
AB  - Weanling female SKH1 hairless mice were randomly divided into 4 groups. Each
      group was fed a particular regimen for 20 weeks: 1) normal basal diet with 5 IU
      vitamin A/g and 0.45 microgram selenium/g, 2) vitamin A deficient, 3) selenium
      deficient, and 4) vitamin A plus selenium deficient. Three hours before being
      sacrificed, half of the animals were subjected to UV A + B irradiation (3 J/cm2).
      Superoxide dismutases (SOD), catalase, Se glutathione peroxidase activities were
      determined in dorsal skin homogenates, as well as the concentrations of GSH and
      of thiobarbituric acid-reactive substances (TBARS), the latter being an index of
      lipid peroxidation. Ultraviolet light altered the antioxidant defense of mouse
      skin tissue: GSH level, catalase and Se glutathione peroxidase activities were
      lowered and SOD was unequally enhanced according to the nutritional status.
      Vitamin A and Se deficiencies did not perceptibly aggravate the UV-induced
      oxidative stress, although the former enhanced the decline of catalase expression
      induced by the irradiation. Probably through an adaptive mechanism, both dietary
      deficiencies increased the skin reserve of antioxidant GSH and thus appear to
      modulate the effects caused by reactive oxygen species.

PMID- 8979159
TI  - Quantitation of vitamin E and a carotenoid pigment in cataractous human lenses,
      and the effect of a dietary supplement.
AB  - The quantitation of tocopherols and carotenoids in lipid extracts of cataractous
      human lenses was performed in parallel with those of matched samples of plasma,
      which was also analysed at the same time. Alpha-tocopherol in cataractous lenses
      from elderly human subjects was present at 4.4 mumoles/kg wet weight, much less
      than the mean of 33 mumoles/l in plasma from these subjects. The mean ratio of
      alpha- and gamma-tocopherols was 3.5 in the lenses, and 11.3 in plasma. Lens
      extracts contained no detectable alpha- or beta-carotene, lycopene, or beta
      cryptoxanthin. However, all the lens extracts contained a pigment with the
      retention time and spectrum of lutein and zeaxanthin. Using the molar extinction
      coefficient of lutein this was present at ca. 0.03 microM, compared with 0.2
      microM in plasma. Seven patients with bilateral cataracts had one of their
      cataractous lenses removed and analysed, and were then given either an oral
      placebo, or an oral supplement of ascorbate, alpha-tocopherol and beta-carotene.
      Three months later, the second cataractous lens, and a blood sample, were
      analysed. Three of the seven had received the active supplement, as confirmed by
      substantially raised blood levels of alpha-tocopherol and beta-carotene, and
      raised aqueous humour levels of vitamin C. However, lens tocopherol levels
      remained unchanged, and no beta-carotene could be detected in the lenses after
      supplementation. This preliminary evidence needs to be confirmed in larger
      studies.

PMID- 8979160
TI  - Changes of phylloquinone and menaquinone-4 concentrations in rat liver after
      oral, intravenous and intraperitoneal administration.
AB  - To study the metabolism of K Vitamins (VK) in the liver, two types of natural VK,
      phylloquinone (K1) and menaquinone-4 (MK-4), were administered to male Wistar
      rats orally (P.O.), intravenously (I.V.) and intraperitoneally (I.P.). Blood and
      a small portion of the liver (and ascites by I.P.) were collected 8 times up to
      72 h (P.O.) or 24 h (I.V. and I.P.). A modified assay procedure followed by high
      performance liquid chromatography (HPLC) was developed to detect VK from small
      amounts of liver tissue. After oral administration of both K1 and MK-4 (10
      mumol/kg-P.O.), their concentrations in the liver increased from 1 h then reached
      a maximum at 6 h (10 nmol/g v.s. 0.35 nmol/g). After intravenous or
      intraperitoneal administration of K1 and MK-4 (0.5 mumol/kg-I.V. and I.P.), MK-4
      concentrations in the liver reached a maximum faster than those of K1 (1.2 nmol/g
      -3 h vs. 1.3 nmol/g -0.5 h I.V. and 0.97 nmol/g -6 h vs. 0.47 nmol/g -1 h I.P.).
      MK-4 also increased in the liver from 6 h to 12 h (0.11 nmol/g -12 h) after oral
      administration of K1 (P.O.). These results indicate that K1 stays in plasma and
      liver longer than MK-4 and orally administered K1 might be transformed partially
      into MK-4 in the liver.

PMID- 8979161
TI  - Vitamin B12 levels in human milk during the first nine months of lactation.
AB  - Vitamin B12 concentration was measured by competitive binding radioassay in 48
      samples of human milk from healthy mothers eating unrestricted diets. Specimens
      were collected 1-35 weeks after full-term delivery and were subjected to
      proteolytic digestion before radioassay in order to destroy binding proteins. The
      distribution of the results was skewed, but the distribution of the logged values
      was not significantly different from normal. The geometric mean vitamin B12 level
      remained almost unchanged during the first 12 weeks postpartum (261-297 pmol/l)
      and then declined to a low of 139 pmol/l at 27-35 weeks. A significant (P =
      0.033) decline in vitamin B12 concentration between 6-12 weeks and 19-25 weeks
      postpartum was observed.

PMID- 8979162
TI  - The study of thiamine requirement in broiler chickens.
AB  - Thiamine status in response to a wide range (2 to 32 mg/kg) of dietary
      supplementation of thiamine was studied in male and female broiler chickens in
      order to understand the manifestation of marginal thiamine deficiency in
      chickens. Thiamine content and transketolase (TK) activity, were measured in
      tissues (brain, heart, liver) and blood samples from chickens at 1, 7, 14, 21,
      35, and 42 days of age. There was no correlation between body weights and tissue
      thiamine or TK activity at 3 or 6 weeks of age. Overall thiamine supplementation
      did not have significant effects on TK activity in the liver (p = 0.22) or brain
      (p = 0.07). Males had a higher concentration of thiamine than females (p < 0.001)
      in livers and brains, but the level in the heart did not differ significantly
      between sexes. There were substantial contrasts among tissues in changes in the
      tissue thiamine content in response to dietary thiamine levels. Relative to day
      1, unsupplemented birds' heart, brain, and liver thiamine increased by 34, 30,
      and 31% respectively. In response to supplementation, the heart tissue tended to
      accumulate thiamine at a considerably higher rate than liver or brain. Blood
      thiamine concentration tended to decline in unsupplemented birds and those
      supplemented at 2 and 4 mg/kg levels, whereas in birds supplemented with 8 mg
      blood thiamine level increased at day 7 and remained relatively constant for the
      remaining part of the trial. Supplementation at the levels of 16 and 32 mg/kg
      resulted in blood thiamine increasing throughout the duration of the trial. The
      presented data indicate that there are organ specific differences in the
      requirement for thiamine. The heart appears to have a higher requirement than the
      liver or brain. Since there are potential beneficial effects of thiamine on the
      heart, this subject deserves more detailed investigation.

PMID- 8979163
TI  - Contributions of food groups to estimated intakes of nutritional elements:
      results from the FDA total diet studies, 1982-1991.
AB  - The contributions of 12 food groups to the estimated dietary intakes of 11
      nutritional elements in the diets of eight age-sex groups was determined from
      analyses of 234 core foods in the U.S. food supply and consumption data from
      national food consumption surveys. The major contributors of each element were
      grain products for sodium, iron, manganese, and iodine; vegetables for potassium;
      milk and cheese for calcium; milk and cheese and animal flesh for phosphorus;
      vegetables and grain products for magnesium; and animal flesh for zinc, copper,
      and selenium. For the infant diet, the milk and cheese group (which includes
      infant formula) was the major contributor to the estimated intakes of sodium,
      potassium, calcium, phosphorus, magnesium, zinc, copper, and iodine. Grain
      products were the primary sources for iron, manganese, and selenium in the infant
      diet. The diet of 2-year-olds, which includes a considerable amount of milk,
      contains larger percentages of sodium, potassium, calcium, phosphorus, magnesium,
      zinc, and iodine from milk and cheese than do the diets of older age-sex groups.
      For teenagers, milk and cheese make a greater contribution to potassium, calcium,
      phosphorus, magnesium, zinc, manganese, and iodine intakes than they do for the
      adult age-sex groups.

PMID- 8979164
TI  - Total diet study: estimated dietary intakes of nutritional elements, 1982-1991.
AB  - Dietary intakes of 11 nutritional elements for eight age-sex groups were
      estimated for the time period 1982 to 1991 on the basis of results from
      laboratory analyses of 234 core foods of the U.S. food supply and food
      consumption data from two national food consumption surveys conducted in the late
      1970s. Estimated intakes based on the mean and median (50th percentile) levels of
      the elements in the foods were similar, except for iodine for which intake
      estimates based on mean values exceeded those based on median values. The high
      concentration of iodine in some foods resulted in higher mean (than median)
      values. Estimated intakes of sodium, potassium, phosphorus, selenium, and iodine
      met or nearly met dietary intake standards set by the National Academy of
      Sciences (NAS). Estimated intakes of copper were below NAS standards for all
      eight age-sex groups. Estimated intakes were below NAS standards for magnesium
      for six age-sex groups, calcium and zinc for five age-sex groups, iron for three
      age-sex groups, and manganese for one age-sex group. The diets of teenage girls
      had seven elements below NAS standards, the diets of adult women had five
      elements below NAS standards, and the diets of 2-year-olds and older men and
      women had four elements each below NAS standards. The estimated intake of sodium
      for 6-11-month-old infants showed a decreasing trend from 729 mg/day in 1982/83
      to 632 mg/day in 1990/91. There were no other significant trends or changes in
      estimated element intakes over the 9-year period.

PMID- 8979165
TI  - Differences in breakfast habits between institutionalized and independent elderly
      Spanish people.
AB  - An investigation was made into the breakfast habits of 150 elderly people between
      65 and 95 years of age. The food intake of 58 institutionalized subjects was
      followed by means of "precise individual weighing of food". The food intake of 92
      subjects living independently was followed using a prospective method involving
      the keeping of a "weighed food record". For all subjects the study lasted 5
      consecutive days including a Sunday. Institutionalized subjects spent more time
      at breakfast (p < 0.01 in women) and the food they consumed was more varied, both
      in terms of number of foods (p < 0.001) and food groups (p < 0.001). Their
      breakfasts included more fruit (P < 0.001), fibre (P < 0.05 in women) and vitamin
      A (P < 0.01) than those of independent subjects, 7% of whom took no breakfast at
      all with a further 8% consuming only a glass of milk or fruit juice. 62.7% of
      independent and 43.1% of institutionalized subjects consumed an inadequate
      breakfast (i.e. their breakfasts provided less than 20% of their energy
      expenditure). The breakfasts of institutionalized subjects contained a greater
      percentage of their total daily intake of carbohydrates (P < 0.001 in women),
      fibre (P < 0.01 in women), thiamine (p < 0.05 in women), vitamin B12 (p < 0.05 in
      women, p < 0.001 in men), vitamin D (p < 0.01 in women) and magnesium (p < 0.05
      in women). Given the importance of breakfast in the maintenance of a satisfactory
      nutritive condition, these results suggest that both qualitative and quantitative
      improvements of elderly people's breakfasts are required. Residing at an old
      people's home seems to improve the quality of breakfast consumed, especially for
      elderly women.

PMID- 8979166
TI  - Dietary intake and anthropometric measures in a Spanish students group.
AB  - Two four-day diet records were used to estimate usual energy and nutrient intake,
      eating patterns (habits) and contribution of meals to total energy intake, in a
      group of 92 biology students from the Granada University. At the same time, a
      series of anthropometric measures was taken from each subject (weight, height,
      skin pleats and arm measurement). Comparison of real intakes with those
      recommended was carried out using the 1980 Spanish recommendations and the 1992
      European Community recommendations. For men (n = 42) mean intakes for most
      nutrients were similar to the recommended levels and the proportion with intakes
      of vitamins and minerals below 80% of the recommended intakes was also minimal.
      Among women (n = 50) mean intake of zinc was below 80% of the Spanish
      recommendation. However, there was a wide range of intakes of minerals and
      vitamins within both groups; therefore, we found a high percentage of subjects
      with intakes of some vitamins or minerals below 80% of the recommended intakes.
      Finally, anthropometric measures showed normal body weight, height, and body
      composition among the students.

PMID- 8979167
TI  - Influence of dietary fish on fatty acid composition of the erythrocyte membrane
      in coronary heart disease patients.
AB  - This study examines the effects of dietary fish oil on the fatty acid composition
      of the erythrocyte membrane in persons with coronary heart disease. Thirty men
      with myocardial infarction were studied during three consecutive periods, during
      which they consumed 1) their habitual diet, 2) a diet specially designed to
      prevent ischaemic cardiopathy, and 3) a diet rich in polyunsaturated fat, in
      which fish was substituted for meat. At the end of each diet, fatty acid
      concentrations in the erythrocyte membrane were measured, and a 48 h recall
      dietary questionnaire was used to determine the types of foods consumed. Despite
      the increase in the intake of (n-3) polyunsaturated fatty acids (PUFA), the fatty
      acid composition of the erythrocyte membrane failed to reflect the greater
      dietary supply of eicosapentaenoic acid, and showed increased concentrations of
      stearic (C16) and palmitic (C18) acid. The increase in dietary (n-3)
      polyunsaturated fatty acids markedly increased 22:4 (n-6), 22:5 (n-6), 22:5 (n-3)
      and 22:6 (n-3) fatty acids.

PMID- 8979168
TI  - Effect of sesame oil on serum and liver lipid profiles in the rat.
AB  - In our previous study (Satchithanandam, S., Reicks, M., Calvert, R.J., Cassidy,
      M.M. and Kritchevsky, D. (1993) J. Nutr. 123, 1852-1858), we found that the
      absorption of lymphatic cholesterol by rats fed diets containing 24% sesame oil
      was about 50% less than that by rats fed the control diet containing no sesame
      oil. The effect of sesame oil on serum cholesterol levels was not determined at
      that time. In the present study, three groups of male Wistar rats (75-100 g) were
      fed a control diet or a diet containing 12 or 24% sesame oil. To increase serum
      cholesterol levels, 1% cholesterol and 0.5% cholic acid were added to each diet.
      After rats were fed for 4 weeks, total cholesterol, LDL-cholesterol, HDL
      cholesterol, and triglyceride levels were measured in the serum. Liver weight and
      cholesterol and triglyceride levels were determined. Liver cholesterol levels
      were significantly lower in rats fed the 24% sesame oil diet, and the liver lipid
      level was significantly higher in the 24% sesame oil-fed group, compared with
      levels in the group fed the control diet. Liver weights and esterified
      cholesterol and liver triglyceride levels were not significantly different among
      the groups. Levels of serum total cholesterol and LDL-cholesterol were
      significantly lower in rats fed the 24% sesame oil diet, compared with levels in
      the control group. Serum triglyceride and HDL-cholesterol levels did not differ
      significantly among the groups. The mechanism by which a diet containing 24%
      sesame oil reduces levels of serum and liver cholesterol, liver LDL cholesterol,
      and liver lipids is not known. However, the high degree of unsaturation (85%) of
      sesame oil and the presence of linoleic acid may be important factors.

PMID- 8979169
TI  - Long-term effects in two generations of enriched soybean and olive oil diets on
      some cardiovascular and biochemical parameters in male rats.
AB  - The effect of ingestion of enriched oil diets (soybean and olive) during two
      generations on some cardiovascular and biochemical parameters was measured in
      male rats. The animals (dams and pups) were fed with 3 different diets: standard
      diet, standard diet enriched with 7% of soybean oil and standard diet enriched
      with 7% of olive oil. At 2.5 months of age, male rats (first and second
      generation) after remaining in metabolic cages for a period of 10 days, were then
      anaesthetized, and body and heart weight, systolic, diastolic, mean blood
      pressure and heart rate, total-cholesterol, HDL-cholesterol, triglycerides,
      glucose and insulin were measured. Experimental diets produced over-weight only
      in the second generation. Blood pressure values were within normal limits, but in
      animals eating soybean oil these parameters were significantly increased in the
      second generation. While the concentrations of cholesterol, triglycerides and
      insulin in the second generation were significantly greater in experimental
      animals, and the concentrations of HDL-cholesterol and glucose were lower than in
      the controls, only the concentration of insulin was significantly greater in the
      experimental animals in the first generation. Plasmatic value of cholesterol was
      significantly increased in animals eating olive oil and plasmatic value of
      glucose was significantly decreased in animals eating soybean oil in the first
      generation. These results suggest that chronic ingestion of enriched oil diets
      negatively affects a number of key parameters implicated in the regulation of
      lipid and carbohydrate metabolism in male rats.

PMID- 8979170
TI  - The effect of fatigue on multijoint kinematics, coordination, and postural
      stability during a repetitive lifting test.
AB  - Because of the inability of strength tests to accurately discriminate between low
      back pain patients and healthy subjects, a multifactorial evaluation of low back
      pain patients is warranted. It is postulated that measurements of endurance,
      kinematics, postural stability, and coordination, in addition to strength, are
      necessary to fully document the patients' functional capabilities. This research
      study was conducted in order to understand the effects of fatigue on the above
      factors. Twelve healthy male subjects performed a repetitive lifting test in
      which a submaximal load was lifted at a maximal rate. Knee, hip, and trunk motion
      was measured using videography and electrogoniometry, postural stability was
      measured using a forceplate, and coordination parameters were determined using
      phase-plane analysis. Fatigue was documented by a 31% reduction in lifting power.
      At the end of the endurance test, there was less knee and hip range of motion and
      greater spine peak flexion, while the coordination measures demonstrated that
      there was greater hip and lumbar spine extension earlier in the lifting phase.
      The postural stability declined as the test endured. Utilization of these
      measures may guide physical therapists in their rehabilitation of low back pain
      patients.

PMID- 8979171
TI  - Static and dynamic balance responses in persons with bilateral knee
      osteoarthritis.
AB  - Research has documented decreased strength and proprioception in people with
      arthritis. Both are components of balance, but reliable studies documenting
      balance deficits have not been done. This study tested standing balance in an
      adult population with osteoarthritis. The osteoarthritic group (N = 11) and the
      age-matched control group (N = 10) were tested on the Balance System. Each
      underwent two trials of six testing conditions [two visual conditions (eyes open,
      eyes closed) under each of three platform conditions (stable, angular rotation,
      and linear translation)] and completed a functional assessment scale. Individuals
      with knee osteoarthritis demonstrated significantly more postural sway than the
      control group across conditions (p < 0.02). The functional assessment scale
      developed to discriminate between the two groups demonstrated internal
      consistency (Cronbach's coefficient alpha = 0.83), and scores were significantly
      different between the two groups (p < 0.0001). Results suggest the importance of
      balance training in this population. The functional assessment scale may be a
      useful tool to document functional levels in knee osteoarthritis.

PMID- 8979172
TI  - Postoperative eccentric and concentric isokinetic strength for the shoulder
      rotators in the scapular and neutral planes.
AB  - Considerable variability exists for isokinetic testing of the shoulder rotators,
      leaving the clinician in a quandry concerning the most appropriate method for
      patient evaluation. The purpose of this study was to evaluate concentric and
      eccentric rotational strength in the scapular and neutral planes for the surgical
      and nonsurgical shoulders. Fifteen males consented to be tested during a 90
      minute isokinetic session. Both shoulders for each patient were tested
      concentrically (240 degrees/sec) and eccentrically (120 degrees/sec) in the
      scapular and neutral planes. Patient positioning was maintained through the use
      of a goniometer, plumb line, and floor grid system. Following a warmup, five
      maximal effort reciprocal internal and external rotation concentric and eccentric
      contractions were evaluated using multiple two-way analyses of variance (shoulder
      x plane) with repeated measures. Results indicated no statistically significant
      differences between the surgical or nonsurgical shoulders for either concentric
      (p = .063-.247) or eccentric (p = .460-.840) modes, regardless of test plane. No
      statistically significant differences were observed eccentrically between test
      planes (p = .06-.470), but the scapular plane produced significantly higher (p =
      .005) peak torques concentrically. Generally, the external rotators were 53.0%
      (concentrically) and 63.0% (eccentrically) of the internal rotator strength for
      either shoulder. Clinically, concentric and eccentric testing of the
      postoperative shoulder patient can occur in either the scapular or the neutral
      plane. However, the scapular plane may be preferred since it is more functionally
      relevant and less injurious to the rotator cuff. A full, functional recovery may
      be expected for the rotator cuff repair patient.

PMID- 8979173
TI  - Concentric and/or eccentric training-induced alterations in shoulder flexor and
      extensor strength.
AB  - To examine the effect of specific concentric and eccentric training on muscular
      strength following an initial standardized period of excessive training, shoulder
      extensors and flexors were tested. The shoulder is a joint particularly
      susceptible to injury and requires a specific strength training program. For a
      period of 12 weeks, subjects performed training, including concentric and
      eccentric actions. Thereafter, they were divided into three groups that performed
      specific 12-week programs, including either concentric (C-E/C), eccentric (C
      E/E), or a combination of both concentric and eccentric exercises (C-E/C-E).
      Following the initial period of training, significant increases (p < 0.05) in
      performance were observed for all experimental groups. The C-E/C group showed
      significant increases (p < 0.05) in performance after 24 weeks of training,
      especially at high concentric angular velocities. However, the C-E/E group showed
      significant increases (p < 0.05) only in their eccentric moments. No significant
      differences were noted for the C-E/C-E group. These findings seem to partly
      confirm the mode-specificity principle, as only the concentric-specific training
      program improved concentric and eccentric strength. Moreover, the velocity
      specificity principle was strongly supported.

PMID- 8979174
TI  - Investigation of the validity and reliability of four objective techniques for
      measuring forward shoulder posture.
AB  - Clinicians often rely on visual inspection and descriptive terms to documents a
      patient's forward shoulder posture. The purpose of this study was to assess the
      validity and intrarater reliability of four objective techniques to measure
      forward shoulder posture. Subjects were 25 males and 24 females. Subjects had a
      lateral cervical spine radiograph taken, from which the horizontal distance from
      the C7 spinous process to the anterior tip of the left anterior acromion process
      was measured. Subjects then proceeded twice through a random order of four
      measurements: the Baylor square, the double square, the Sahrmann technique, and
      scapular position. These results were then used to determine the intrarater
      reliability of each technique. Multiple regression analyses were performed on
      each measure's mean scores to determine both the correlation with and the
      predictive value for the radiographic measurement. The intraclass correlation
      coefficients for intrarater reliability ranged from .89 to .91. The correlation
      coefficients ranged from -.33 to .77, and the coefficients of determination
      ranged from .10 to .59 (N = 49). The researchers demonstrated clinical
      reliability for each technique; however, validity compared with the radiographic
      measurement could not be established. These techniques may have clinical value in
      objectively measuring change in a patient's shoulder posture as a result of a
      treatment program. Before any of these measures could be universally recommended
      in clinical practice, future research is necessary to establish interrater
      reliability and assess each technique's ability to detect postural changes over
      time.

PMID- 8979175
TI  - The clinical and cost-effectiveness of two different programs for rehabilitation
      following ACL reconstruction.
AB  - Patient rehabilitation following anterior cruciate ligament reconstruction is a
      continuing challenge for physical therapists. This study compared the
      effectiveness of an established protocol to a new program which included
      Protonics exercise. Sixty patient (42 males and 18 females; mean age = 24.7 +/-
      3.9 years; age range = 19-30 years) were randomly assigned into two groups: Group
      1 received the established protocol and Group 2 received a Protonics exercise
      regimen. Both groups were measured for the time needed for return to unrestricted
      activity on the basis of objective, functional, and clinical exams; all tests
      were repeated at a 1-year follow-up exam. Group 2 completed treatment an average
      of 3.3 weeks sooner than Group 1 (mean = 19.8 vs. 23.1 weeks) at an average lower
      cost of $990.00 per subject. All subjects had good functional outcomes at the 1
      year follow-up exam. It was concluded that the Protonics exercise program was
      more clinically and cost-effective than the other program, although both methods
      were successful for postsurgical anterior cruciate ligament rehabilitation.

PMID- 8979176
TI  - A measurement of anterior tibial displacement in the closed and open kinetic
      chain.
AB  - Anterior displacement of the tibia during knee extension movement has been
      identified as a possible factor in anterior cruciate ligament (ACL)
      reconstruction failure due to the increased stress placed on the graft, leading
      to a creep response in the healing graft. Nineteen healthy subjects with a
      unilateral ACL deficiency were evaluated in an open and closed kinetic chain. A
      KT-1000 was used to measure anterior displacement of the tibia on the femur
      during isometric open and closed kinetic chain exercise at 30 and 60 degrees. An
      analysis of variance for repeated measures followed by Newman-Keuls multiple
      comparison tests were performed to determine the differences between the open and
      closed kinetic chain for the involved and uninvolved knee. Statistically
      significant differences were found when comparing the amount of anterior
      displacement between the open and closed kinetic chain for the involved and
      uninvolved knee at 30 and 60 degrees. Clinicians utilizing isometric exercise in
      rehabilitation of the anterior-cruciate-deficient and the anterior-cruciate
      reconstructed patient should be aware of the increased amount of anterior tibial
      displacement when comparing open and closed kinetic chain exercise.

PMID- 8979177
TI  - Fetal/neonatal neurologic injury and "ACOG Technical Bulletin 163": a light at
      the end of the tunnel.

PMID- 8979178
TI  - Combined effects of antenatal corticosteroids and surfactant supplementation on
      the outcome of very low birth weight infants.
AB  - Antenatal corticosteroids in preterm pregnancy may result in the reduction of the
      incidence of respiratory distress syndrome (RDS) and neonatal mortality. It is
      well known that postnatal use of surfactant in very low birth weight (VLBW)
      infants with RDS results in decreased neonatal morbidity and mortality. To
      evaluate the additive beneficial effects of combined antenatal corticosteroids
      and postnatal use of rescue surfactant on the outcome of VLBW infants, we
      retrospectively reviewed 286 maternal/infant charts of preterm infants with
      gestational ages 23 to 32 weeks and birth weights 501 to 1500 gm who were born at
      our institution from 1991 through 1994. Of the 87 (30%) infants who were treated
      with corticosteroids before birth, 41 (47%) had RDS, and of the 199 (70%) infants
      who were not treated with corticosteroids before birth, 162 (81%) had RDS (p <
      0.001). The infants who had RDS and who were treated with corticosteroids before
      birth had a decreased incidence of pulmonary air leaks and a decreased need for
      diuretic therapy. In addition, they had a significant reduction in O2 requirement
      and ventilator settings as reflected by FIO2, mean airway pressure, ventilator
      rate, O2 index, and A-aDO2 before they received the first dose of rescue
      surfactant (p < 0.05 to p < 0.01) in contrast to other VLBW infants who had RDS
      and who were not treated with corticosteroids before birth. We conclude that
      antenatal corticosteroid therapy in threatened premature labor combined with the
      use of postnatal rescue surfactant is associated with a decreased incidence of
      RDS and may be beneficial for reducing the severity of RDS and improving the
      eventual outcome of VLBW infants.

PMID- 8979179
TI  - Physician opinions of preterm infant outcome and their effect on antenatal
      corticosteroid use.
AB  - Our purpose was to compare physician opinions about the appropriate use of
      corticosteroids with physician perceptions of preterm infant outcome. A total of
      409 obstetricians and family physicians who provide maternity care in Alabama
      were surveyed to determine whether (and how) their perceptions of preterm infant
      outcome influenced their decision to use antenatal corticosteroids. Results were
      compared with those of a similar survey of Alabama physicians conducted in 1979.
      A total of 85% of physicians in 1992 versus 61% in 1979 reported that situations
      existed in which they would prescribe antenatal corticosteroids (p < 0.001). In
      1992 physicians who underestimated preterm infant survival began corticosteroid
      use at later gestational ages than those physicians who did not underestimate
      survival (p < 0.02). In addition, 54% of physicians who underestimated preterm
      infant survival reported giving corticosteroids between 23 and 28 weeks'
      gestational age versus 73% of physicians with more accurate perceptions (p <
      0.03). We conclude that in 1992, compared within 1979, more Alabama physicians
      reported antenatal corticosteroid use. Use of this treatment was influenced by
      each physician's perceptions of the probable outcome of the preterm infant.

PMID- 8979180
TI  - The effect of maternal smoking during pregnancy on sleep respiratory and arousal
      patterns in neonates.
AB  - Ten term infants who were exposed to maternal smoking during pregnancy and 10 age
      and sex-matched control infants participated in the study. At the age of 48
      hours (+/- 10), all infants underwent a 150- to 200-minute polygraphic study in a
      soundproof laboratory. Respiratory and heart rates, distribution of sleep states,
      and oxygen saturation were comparable in the two groups. The number and length of
      apneic events were similarly distributed in the two groups. The proportion of
      obstructive apneic events followed by arousal was significantly higher in the
      control group especially during quiet sleep (p = 0.001). It appears that exposure
      to smoking during pregnancy is associated with a higher arousal threshold in term
      infants. This finding could be of relevance in the assessment of maternal smoking
      as a risk factor for sudden infant death syndrome.

PMID- 8979181
TI  - Survival and neutrophil kinetics in infants with severe group B streptococcal
      disease treated with gamma globulin.
AB  - To estimate the efficacy of intravenous gamma globulin adjunct therapy on the
      course of severe neonatal group B streptococcal (GBS) disease, the hospital
      records of 67 confirmed cases of early-onset GBS sepsis associated with
      neutropenia were reviewed. Among the 33 infants who had received antibiotic
      agents without gamma globulin, 13 (39%) died. Among the 34 who had received
      antibiotic agents plus gamma globulin, 6 (18%) died (p < 0.05). Among 52 low
      birth weight infants, 5 (20%) of the 25 given gamma globulin died compared with
      13 (48%) of the 27 not given gamma globulin (p < 0.03). Neutrophil counts rose
      more rapidly among survivors who received gamma globulin than among those who did
      not. This retrospective study suggests that intravenous gamma globulin adjunct
      therapy for neonatal GBS disease associated with neutropenia promotes a more
      rapid increase in neutrophil count and improves survival.

PMID- 8979182
TI  - Nitrovasodilator therapy for severe respiratory distress syndrome.
AB  - Improved gas exchange in infants with severe respiratory distress syndrome has
      been reported in association with infusion of nitroprusside and during inhalation
      of nitric oxide. To evaluate the association between nitrovasodilator therapy and
      clinical improvement in premature neonates with severe respiratory distress
      syndrome, we reviewed the courses of 22 infants with severe respiratory distress
      syndrome who were treated with sodium nitroprusside for at least 24 hours. These
      infants had birth weights of 2049 +/- 828 gm (range 720 to 3430 gm), gestational
      ages of 32.5 +/- 3.5 weeks (range 25 to 38 weeks), high ventilator settings
      before treatment (FIO2 of 100%, peak inspiratory pressures of 37.8 +/- 6.1 cm H2O
      [range 30 to 50 cm H2O], and mean airway pressures of 18.0 +/- 3.3 cm H2O [range
      12.3 to 26 cm H2O]), and low pretreatment PaO2 of 49.3 +/- 9.4 mm Hg (range 27 to
      69 mm Hg). Baseline oxygenation indexes were 39.4 +/- 12.1 (range 18.6 to 66.7).
      Nitroprusside infusion was temporally associated with increased PaO2, decreased
      PaCO2, and reduced oxygenation index. Potentially beneficial changes were
      inconsistent in infants with pulmonary interstitial emphysema and were greatest
      in infants treated with end-expiratory pressures of at least 4 cm H2O. These
      observations provide a basis for the hypothesis that nitrovasodilator therapy
      produces improvement in gas exchange in premature infants with severe respiratory
      distress syndrome.

PMID- 8979183
TI  - Testing cord blood human chorionic gonadotropin as a surrogate marker for early
      identification of human immunodeficiency virus-1 infection in children.
AB  - We measured human chorionic gonadotropin (hCG) in cord sera of 22 infants born to
      women infected with the human immunodeficiency virus-1 (HIV-1). hCG was also
      determined in cord sera from 173 infants born at a suburban hospital to HIV-1
      seronegative women. The findings indicate that 16 (9%) of 173 HIV-1-seronegative
      samples had hCG levels greater than 90 IU/L (values were distributed as a Poisson
      curve). In contrast, 8 (36%) of the 22 infants born to HIV-1-infected women had
      hCG levels in excess of 90 IU/L, and 7 (88%) of these were shown to be HIV
      infected. The remaining 14 infants born to HIV-1-infected women had low hCG
      levels, and 3 (21%) of the 14 had HIV infection. Mean follow-up time for HIV
      uninfected infants was 17.5 months (range 9 months to 3 years). A statistically
      significant association between maternal-fetal HIV-1 transmission and hCG levels
      > or = 90 IU/L in cord sera was observed (p = 0.02). The difference between CD4
      counts among mothers who transmitted HIV and those who did not was also
      statistically significant (p = 0.025). On the basis of this study's findings, we
      propose that cord blood hCG may serve as a surrogate marker for HIV-1 infection.
      Testing hCG levels in cord sera is an inexpensive and readily available screening
      test for early identification of infants at increased risk for getting HIV-1 from
      their mothers.

PMID- 8979184
TI  - Clinical examination findings in neonates with the absence of electrocerebral
      activity: an acute or chronic encephalopathic state?
AB  - Although the presence of an isoelectric electroencephalogram (EEG) in an older
      patient may reflect brain death caused by an acute brain injury, this
      electrographic abnormality may appear in more diverse clinical situations in the
      neonate with encephalopathy. During a 6-year period, 20 neonates were identified
      with a severe encephalopathy on neurologic examination who had at least one
      isoelectric EEG during their treatment in a neonatal intensive care unit. Seventy
      four EEG recordings were obtained including 36 isoelectric EEG records. Partially
      preserved clinical brain function was present in 15 (75%) of 20 infants at the
      time an isoelectric EEG was obtained. The initial EEG was isoelectric in 16 of 20
      infants. Although electrographic activity reemerged in nine of these infants,
      significant clinical improvement was seen in only two patients. Thirteen of 20
      neonates also had electrographic or other evidence of clinical seizures. Of the
      five survivors (25%), three had severe neurologic sequelae. The remaining two had
      either transient or persistent neurologic deficits. An isoelectric EEG may be
      obtained in the neonate with partially preserved brain function and, therefore,
      may not be a reliable confirmatory test of neonatal brain death. In addition,
      serial EEGs not only can help assess the severity of a neonatal encephalopathy
      but also may correlate with chronic and acute neurologic insults.

PMID- 8979185
TI  - Intravenous access in newborn infants: impact of extended umbilical venous
      catheter use on requirement for peripheral venous lines.
AB  - Central venous lines are used to care for critically ill neonates in cases of
      limited peripheral venous access. This prospective, randomized study evaluated
      the risks and benefits of the use of single- and double-lumen umbilical venous
      catheters for up to 14 days. Patients were randomized to one of three treatment
      arms: (1) single-lumen umbilical catheter, (2) double-lumen umbilical catheter,
      or (3) no umbilical catheter; peripheral intravenous lines only. Infants in the
      groups treated with an umbilical venous catheter had significantly fewer
      venipunctures and peripheral intravenous lines placed during their first 2 weeks
      of life than those in the peripheral line only group. Less time and money were
      spent obtaining peripheral line placement in the umbilical venous catheter
      groups. The incidence rates of sepsis and complications were not higher in
      treated patients than in control patients. The double-lumen catheter further
      reduced peripheral venipunctures and lines. We conclude that an umbilical venous
      catheter used during the first 2 weeks of life is a relatively safe, less
      stressful, cost-effective means of providing intravenous therapy to neonates.

PMID- 8979186
TI  - A study of resistive indices in the arcuate arteries of the kidney over the
      course of gestation.
AB  - OBJECTIVE: Our purpose was to assess whether there was a variation in the
      resistive index (RI) of the arcuate artery in the kidneys of patients with
      hydronephrosis in pregnancy. STUDY DESIGN: Forty-seven patients were studied to
      establish norms for the RI of the arcuate arteries in pregnancy, and these
      measurements were correlated with the development of hydronephrosis over the
      course of gestation. RESULTS AND CONCLUSIONS: The RIs were noted to remain
      unchanged from the nonpregnant state throughout gestation. They were also
      unchanged by the presence of the physiologic hydronephrosis of pregnancy.

PMID- 8979187
TI  - Management of neonates born to mothers with group B streptococcus colonization.
AB  - Approximately 20% of pregnant women harbor group B streptococcus (GBS) in the
      lower genital tract at the time of delivery. Intrapartum chemoprophylaxis of
      mothers with GBS colonization who have risk factors for neonatal GBS at delivery
      improves the outcome of the neonates. The recommendations for treating newborn
      infants of mothers who receive intrapartum chemoprophylaxis for GBS colonization
      and the recommendations for those who do not remain empiric, because clinical
      studies to support such recommendations are not available. An algorithm for
      treatment of neonates born to mothers with GBS colonization that is based on
      available data and empiric recommendations is presented. These guidelines are
      intended to guide medical practice and not to replace clinical judgment.

PMID- 8979188
TI  - Hydatid mole with a coexisting pregnancy.
AB  - Hydatid mole with a coexisting pregnancy is rare and presents a high risk for
      maternal and fetal morbidity and mortality. A case of hydatid mole with
      coexisting pregnancy that progressed to 24 weeks' gestation is presented.
      Maternal religious beliefs regarding pregnancy termination affected the medical
      plan of care. Although the woman was aware of the potential complications,
      pregnancy termination and karyotype testing were refused. Because of
      uncontrollable hemorrhage, a cesarean delivery was done. The genotypically normal
      fetus died 10 hours after birth. After delivery, preeclampsia, pulmonary edema,
      and renal failure developed in the woman, which resolved within 4 days.

PMID- 8979189
TI  - What is continuous nebulized albuterol?

PMID- 8979190
TI  - Supply and demand for neonatal intensive care: trends and implications.
AB  - OBJECTIVE: Access to high-risk newborn care is determined by supply of services,
      demand, and financing. Major changes in health care have occurred since the
      advent of perinatal regionalization in the mid-1970s. This article explores
      access from the point of view of the supply and demand for neonatal intensive
      care within the changing financing environment. STUDY DESIGN: An analysis was
      done of the 1983, 1989, and 1991 American Hospital Association survey data,
      combined with birth data from the National Center for Health Statistics. RESULTS:
      By 1991 supply of hospital-based high-risk newborn care exceeded demand;
      nationally, there were roughly 300,000 excess bed-days available in 1991.
      Regional figures revealed that these estimates are, if anything, conservative.
      CONCLUSIONS: Payers are increasingly price sensitive and have the ability to
      shift blocks of patients from one facility to another. A surplus encourages a
      shift of patients to low-price locations. Differentiation of quality and
      monitoring will become an important means of ensuring access to high-quality care
      in a surplus environment.

PMID- 8979191
TI  - Neonatal fellowship. Neonatal pneumopericardium: successful treatment with
      nitrogen washout technique.
AB  - Pneumopericardium in the neonate is a rare event but is associated with
      significant morbidity and mortality. We describe a neonate with mild respiratory
      distress and cardiovascular compromise after delivery and resuscitation. A large
      isolated pneumopericardium was diagnosed. Treatment with an oxygen hood (FiO2
      1.00) resulted in a complete resolution of the pneumopericardium within 12 hours.

PMID- 8979192
TI  - Intrauterine stroke, cerebral injury, and seizures.

PMID- 8979193
TI  - Renal tubular dysgenesis: a report of two cases.
AB  - Renal tubular dysgenesis, a congenital disorder of renal tubular development, was
      diagnosed in two newborns with oligohydramnios and Potter phenotype. Renal
      tubular dysgenesis (RTD) is a recently recognized congenital disorder of renal
      tubular development associated with oligohydramnios, Potter phenotype, and
      neonatal respiratory and renal failure. We report two newborn siblings with
      typical clinical and anatomic features of RTD. The diagnosis was proven by
      autopsy in one child. The pediatrician should consider the diagnosis of RTD in a
      child with congenital anuria and structurally normal kidneys on ultrasound,
      especially if a maternal history of late trimester oligohydramnios is present.

PMID- 8979194
TI  - Ventilatory management casebook. Resolution of pulmonary interstitial emphysema
      using a balloon catheter.

PMID- 8979195
TI  - Special imaging casebook. Cerebrocostomandibular syndrome with hypoxic
      myocardiopathy and encephalopathy.

PMID- 8979196
TI  - Perinatal pathology casebook. A case of twin transfusion syndrome with
      dichorionic placentas.

PMID- 8979198
TI  - Notes on oximeter.

PMID- 8979197
TI  - Primary hyperparathyroidism and pregnancy.

PMID- 8979199
TI  - Voiding function following prolapse surgery. Impact of estrogen replacement.
AB  - OBJECTIVE: To identify factors that would predict postoperative bladder function
      in postmenopausal women undergoing pelvic reconstructive surgery for pelvic organ
      prolapse. STUDY DESIGN: Demographic variables and urodynamic measures were
      analyzed in respect to the length of postoperative bladder catheterization.
      RESULTS: Patient age, the presence of abnormal preoperative voiding patterns or
      elevated postvoid residuals, the route of surgical approach and the performance
      of urethropexy did not correlate significantly with the length of postoperative
      catheterization; only hormonal status did. Postmenopausal women using estrogen
      replacement therapy required significantly fewer days of catheterization than
      those who were not receiving estrogen replacement therapy. CONCLUSION: The use of
      preoperative estrogen replacement therapy is associated with a reduction in the
      length of postoperative bladder catheterization in women undergoing pelvic
      reconstructive surgery for pelvic organ prolapse.

PMID- 8979200
TI  - Detecting GD and preeclampsia. Effectiveness of routine urine screening for
      glucose and protein.
AB  - OBJECTIVE: To assess why urine collection and analysis for proteinuria and
      glycosuria is routinely performed during each antepartum visit at prenatal
      clinics. STUDY DESIGN: Six hundred ten antepartum medical records were reviewed.
      RESULTS: One hundred nine (18%) patients had proteinuria, while 17 patients
      (2.8%) developed preeclampsia. Fifteen patients (2.5%) had at least one episode
      of glycosuria (100 mg/dL), while 11 had gestational diabetes. Of those with
      gestational diabetes, four (36%) had glycosuria. Of those with preeclampsia,
      three (17.7%) had proteinuria that preceded the finding of hypertension.
      CONCLUSION: These results support our observation that routine oral 50-g glucose
      diabetes screening and careful monitoring of blood pressure are better screens
      for gestational diabetes and preeclampsia. The increased patient inconvenience
      and clinic staffing necessary for routine urinalysis may be avoided by
      eliminating that ritual.

PMID- 8979201
TI  - Increasing clinical pregnancy rates after IVF/ET. Can immunosuppression help?
AB  - OBJECTIVE: To evaluate the safety and efficacy of immunosuppression as an adjunct
      to improving the success of in vitro fertilization/embryo transfer (IVF-ET).
      STUDY DESIGN: A randomized, double-blind, placebo-controlled clinical trial.
      RESULTS: Seventy-five patients were randomized to receive either prednisone (39
      patients, 51%) or placebo (36 patients, 49%). Patients in both groups had similar
      ages and numbers of preembryos transferred. CONCLUSION: Both the implantation and
      clinical pregnancy rates were higher in the prednisone group (16% vs. 11% and
      43.5% vs. 32.3%, respectively). However, these differences did not achieve
      statistical significance. Evaluation of the ongoing pregnancy rate revealed
      little difference between the prednisone-treated patients (30.7%) and those
      receiving placebo (28.0%). There were no side effects reported by patients in
      either group.

PMID- 8979202
TI  - Endometrial biopsy in DUB.
AB  - OBJECTIVE: To determine the incidence of abnormal endometrial histology in women
      with dysfunctional uterine bleeding and to evaluate the predictive value of risk
      factors for endometrial cancer in women with dysfunctional uterine bleeding
      (DUB). STUDY DESIGN: We conducted a retrospective review of 310 women with DUB
      who underwent endometrial biopsy. The risk factors for abnormal endometrial
      histology included menstrual cycle irregularity, diabetes, nulliparity,
      hypertension, weight > or = 100 kg and age > or = 40 years. The incidence of
      endometrial abnormalities was determined, and the predictive value of
      combinations of risk factors was assessed using stepwise logistic regression.
      RESULTS: Twenty-one patients (6.7%) had abnormal endometrial biopsies. Menstrual
      cycle irregularity (P = .0001), age > or = 40 years (p = .022) and hypertension
      (P = .058) were independently significant risk factors for abnormal endometrial
      histology. The probability of abnormal endometrial histology in a premenopausal
      woman with DUB whose cycle was regular was < 1%. The presence of menstrual cycle
      irregularity increased the probability of abnormal endometrial histology to
      14.3%. CONCLUSION: The patient who presents with DUB and a history of menstrual
      cycle irregularity warrants an endometrial biopsy, regardless of age. The current
      clinical emphasis on age (especially > or = 40 years) as justification for
      endometrial biopsy is unwarranted in patients with DUB. More careful selection of
      patients for endometrial biopsy will mean that fewer women are unnecessarily
      exposed to the discomfort and risk of complications associated with endometrial
      biopsy.

PMID- 8979203
TI  - Managing pregnancy-related nocturnal nasal congestion. The external nasal
      dilator.
AB  - OBJECTIVE: To assess the efficacy of an over-the-counter mechanical nasal dilator
      during sleep in pregnant women with nasal congestion. STUDY DESIGN: Pregnant
      women with symptoms of nocturnal nasal congestion not attributed to allergies or
      "cold" symptoms were randomized in a double-blind manner to receive either a
      spring-loaded device or placebo device without a spring. Each patient assessed
      breathing and sleep quality for a three-day baseline and three-day treatment
      period. A 10-question diary was utilized to assess breathing, ease of falling
      asleep, sleep quality, and continuity and depth of sleep. Averaged scores for
      each question were computed for baseline and treatment periods, and differences
      were calculated. Statistical analyses were by the sign test, Fisher's exact test
      and Student's test. RESULTS: Thirty-four (21%) of 160 screened patients were
      enrolled into the study; 24 (15%) completed the study. All agreed to being
      assigned to receive either the spring-loaded device (n = 12) or a placebo (n =
      12) device. Responses to 8 of the 10 questions favored the former as compared
      with the placebo (P = .05, sign test). Moreover, patients treated with the spring
      loaded device gave more favorable responses to the question, "Overall, compared
      with most nights, how easy was your breathing through-out last night?" (P = .02,
      t test). CONCLUSION: Use of this drug-free external nasal dilator improved the
      ease of breathing among patients with pregnancy-related nocturnal congestion.

PMID- 8979204
TI  - Preterm delivery after indomethacin. A risk factor for neonatal complications?
AB  - OBJECTIVE: To determine if tocolytic therapy with indomethacin is associated with
      an increased risk of neonatal complications in infants born prior to 32 weeks'
      gestation. STUDY DESIGN: We performed a retrospective matched cohort study of
      infants born between 24 and 31(6)/7 weeks' gestation. The 62 cases (indomethacin
      treatment) and the 62 controls were matched by week of gestation, prenatal
      betamethasone exposure and multifetal gestation. RESULTS: The mean gestational
      age of the two groups was 28.5 +/- SD weeks. The median total dose of
      indomethacin was 425 mg, the median treatment duration was three days, and the
      median interval from the last dose of indomethacin until delivery was one day.
      There was no significant difference between the groups in the incidence of
      necrotizing enterocolitis, intraventricular hemorrhage, patent ductus arteriosis,
      sepsis or neonatal death. CONCLUSION: The use of indomethacin for tocolysis was
      not associated with an increased risk of neonatal complications in infants born
      between 24 and 31(6)/7 weeks' gestation.

PMID- 8979205
TI  - Accuracy of intrapartum estimates of fetal weight. Effect of oligohydramnios.
AB  - OBJECTIVE: To study the effect of oligohydramnios on the accuracy of intrapartum
      clinical and sonographic estimates of fetal weight (EFWs). STUDY DESIGN:
      Intrapartum clinical and sonographic EFWs and an amniotic fluid index (AFI) were
      obtained on 124 term patients. Oligohydramnios was defined as an AFI < or = 5 cm.
      RESULTS: Clinical and sonographic EFWs in women with oligohydramnios were
      significantly less accurate than estimates derived in patients with normal
      amniotic fluid: P = .03 and .02, respectively. The incidence of clinical and
      sonographic EFWs within +/-10% of the actual birth weight were 70.1% and 68.4%,
      respectively (P = NS). CONCLUSION: In term patients, intrapartum sonographic
      prediction of birth weight offers no advantage over estimated fetal weight
      obtained by abdominal palpation. The presence of oligohydramnios significantly
      reduces the accuracy of intrapartum clinical as well as sonographic EFWs.
      Therefore, we suggest that intrapartum EFWs be obtained prior to artificial
      rupture of the membranes.

PMID- 8979206
TI  - Extraperitoneal cystotomy after laparoscopy. A case report.
AB  - BACKGROUND: Difficult laparoscopic entry with preperitoneal dissection may
      disrupt the bladder wall without intraperitoneal or transvaginal evidence of
      injury. A high index of suspicion must be maintained. CASE: A laparoscopically
      assisted vaginal hysterectomy was performed on a 136-kg, 43-year-old nullipara
      with a fibroid uterus and pelvic endometriosis. Open laparoscopic entry was
      impeded by a distorted abdominal wall, necessitating infraumbilical,
      extraperitoneal laparoscopic dissection. Following an uncomplicated
      laparoscopically assisted vaginal hysterectomy, gross hematuria was evident.
      Intravesically instilled methylene blue would not leak transvaginally or
      intraperitoneally. Extraperitoneal prevesical laparoscopic inspection
      demonstrated an anterior cystotomy that was repaired endoscopically. CONCLUSION:
      This report highlights the potential dangers of inadvertent vesical injury in the
      laparoscopic patient with difficult entry as well as the failure of traditional
      transvaginal or transabdominal diagnostic maneuvers to reliably identify
      extraperitoneal bladder injuries. The report also suggests a mechanism by which
      surgically inapparent vesicoabdominal trocar fistulas may form and confirms that
      bladder injuries, in selected patients, can be safely and effectively repaired
      laparoscopically.

PMID- 8979207
TI  - Posthysterectomy fallopian tube herniation. A report of two cases.
AB  - BACKGROUND: Tubal herniation as a complication of hysterectomy is a rare
      phenomenon, markedly more frequent after vaginal hysterectomy. With the
      increasing use of the vaginal route, the ratio between tubal herniation after
      vaginal versus abdominal hysterectomy may exceed 3:1. CASE: We report two cases
      of tubal herniation into the vagina, one after vaginal hysterectomy and the other
      after total abdominal hysterectomy, in two patients, aged 36 and 37 years.
      CONCLUSION: A tubal prolapse in the vagina may be considered a hernia and occurs
      only if a communication exists between the peritoneal cavity and vaginal canal.
      It can be an early or late prolapse. Symptoms consist almost exclusively of
      persistent blood loss and/or leukorrhea, dyspareunia and chronic pelvic pain.
      Whether the abdominal or vaginal approach should be used in surgical correction
      of prolapsed tubes must be decided in each case according to the patient's
      individual characteristics. Both histologic pictures described merit careful
      attention, distinguishing between the terminal tubal segment and the more cranial
      tract (above the vaginal strangulation).

PMID- 8979208
TI  - Diverticulitis mimicking a tuboovarian abscess. Report of a case in a young
      woman.
AB  - BACKGROUND: Diverticulitis is an uncommon condition in young women. When it
      occurs, it is often not recognized until complications such as perforation or
      fistulization occur. There has been no recent discussion in the gynecologic
      literature of diverticulitis in a young woman presenting as gynecologic disease.
      CASE: A 31-year-old woman with a long history of "irritable bowel syndrome"
      developed a 4-5-cm left adnexal mass associated with mild discomfort and
      dysparunia. Acute worsening of her pain led to abdominal exploration and left
      salpingo-oophorectomy for an unruptured tuboovarian abscess. She initially
      improved but then developed a recurrent pelvic abscess. Workup revealed extensive
      diverticulosis with probable sigmoid diverticulitis. Reexploration, drainage of
      the abscess and fecal diversion were required. CONCLUSION: Because of the
      proximity of the left ovary to the sigmoid colon, it is possible for
      diverticulitis to perforate into the ovary, producing a tuboovarian abscess
      indistinguishable from that due to other more common causes. A high index of
      suspicion is required to make the diagnosis, especially in young women. Failure
      to treat underlying diverticulitis can lead to persistent or recurrent pelvic
      infection.

PMID- 8979209
TI  - Testosterone-producing benign cystic teratoma with virilism. A case report.
AB  - BACKGROUND: Mature cystic teratomas are common tumors in reproductive-age women.
      Biologic activity in a small percentage of these neoplasms is well recognized.
      Thyroid hormone is the most commonly secreted substance. CASE: A 25-year-old
      woman presented with a large abdominal mass and virilism. Preoperative evaluation
      revealed elevated creatinine and testosterone levels and anemia. Computed
      tomography (CT) showed fat-fluid levels and multiple calcifications within the
      mass and obstruction of the right kidney. At surgery a 30-cm left ovarian mass
      was removed. Left ovarian vein testosterone levels were markedly elevated.
      Pathology reported a mature cystic teratoma. Postoperatively the testosterone
      levels returned to normal. CONCLUSION: In rare instances androgen production and
      virilization may occur with mature cystic teratoma.

PMID- 8979210
TI  - Matching Alcoholism Treatments to Client Heterogeneity: Project MATCH
      posttreatment drinking outcomes.
AB  - OBJECTIVE: To assess the benefits of matching alcohol dependent clients to three
      different treatments with reference to a variety of client attributes. METHODS:
      Two parallel but independent randomized clinical trials were conducted, one with
      alcohol dependent clients receiving outpatient therapy (N = 952; 72% male) and
      one with clients receiving aftercare therapy following inpatient or day hospital
      treatment (N = 774; 80% male). Clients were randomly assigned to one of three 12
      week, manual-guided, individually delivered treatments: Cognitive Behavioral
      Coping Skills Therapy, Motivational Enhancement Therapy or Twelve-Step
      Facilitation Therapy. Clients were then monitored over a 1-year posttreatment
      period. Individual differences in response to treatment were modeled as a latent
      growth process and evaluated for 10 primary matching variables and 16 contrasts
      specified a priori. The primary outcome measures were percent days abstinent and
      drinks per drinking day during the 1-year posttreatment period. RESULTS: Clients
      attended on average two-thirds of treatment sessions offered, indicating that
      substantial amounts of treatment were delivered, and research follow-up rates
      exceeded 90% of living subjects interviewed at the 1-year posttreatment
      assessment. Significant and sustained improvements in drinking outcomes were
      achieved from baseline to 1-year posttreatment by the clients assigned to each of
      these well-defined and individually delivered psychosocial treatments. There was
      little difference in outcomes by type of treatment. Only one attribute,
      psychiatric severity, demonstrated a significant attribute by treatment
      interaction: In the outpatient study, clients low in psychiatric severity had
      more abstinent days after 12-step facilitation treatment than after cognitive
      behavioral therapy. Neither treatment was clearly superior for clients with
      higher levels of psychiatric severity. Two other attributes showed time-dependent
      matching effects: motivation among outpatients and meaning-seeking among
      aftercare clients. Client attributes of motivational readiness, network support
      for drinking, alcohol involvement, gender, psychiatric severity and sociopathy
      were prognostic of drinking outcomes over time. CONCLUSIONS: The findings suggest
      that psychiatric severity should be considered when assigning clients to
      outpatient therapies. The lack of other robust matching effects suggests that,
      aside from psychiatric severity, providers need not take these client
      characteristics into account when triaging clients to one or the other of these
      three individually delivered treatment approaches, despite their different
      treatment philosophies.

PMID- 8979211
TI  - Sleep in detoxified alcoholics: impairment of most standard sleep parameters and
      increased risk for sleep apnea, but not for myoclonias--a controlled study.
AB  - OBJECTIVE: To assess recently alcohol-abstinent chronic alcoholic patients for
      selected parameters indicative of sleep quality. METHOD: Patients (n = 24, 14
      male), abstinent 3-6 weeks, and healthy controls (n = 20) were admitted to a
      clinical sleep unit. Measurements included sleep respiratory events and periodic
      limb movements, using strict methodology. RESULTS: Clear signs of sleep
      deterioration and a high prevalence of apneic/hypopneic episodes were observed.
      Apneas were found at the same frequency for men and women; this has not been
      described before. No periodic limb movement was found. CONCLUSIONS: Considering
      the high degree of morbidity and mortality observed in sleep apneic syndrome,
      systematic screening for sleep apneas is recommended for alcoholics seeking help.

PMID- 8979212
TI  - The relationship of drinking and hangovers to workplace problems: an empirical
      study.
AB  - OBJECTIVE: This article reports on the relationship between drinking patterns and
      workplace problems in a manufacturing facility operated by a Fortune 500
      industry. METHOD: The data come from a survey of 832 hourly employees (88% male)
      and from ethnographic research in the plant. This study is distinctive because it
      examined a large random sample of workers, rather than an impaired subpopulation.
      Moreover, the study is among the few that has asked employees how much they drank
      prior to and during working hours and how frequently they had been hungover at
      work. Respondents were also asked about their overall alcohol consumption and
      their experience of various problems in the workplace. RESULTS: Bivariate
      analyses indicated that overall drinking, heavy drinking outside of work,
      drinking at or just before work and coming to work hungover were related to the
      overall number of work problems experienced by respondents, and to specific
      problems such as conflicts with supervisors and falling asleep on the job.
      Multivariate analyses revealed that workplace drinking and coming to work
      hungover predicted work-related problems even when usual drinking patterns, heavy
      drinking and significant job characteristics and background variables were
      controlled. Overall drinking and heavy drinking outside the workplace did not
      predict workplace problems in the multivariate analyses. The analyses show that
      workplace problems were also related to age, gender, ethnicity, work shift and
      departments. Survey results are explicated with findings from a plant
      ethnography. CONCLUSIONS: Although the relationships are modest, they support the
      hypothesis that work-related drinking and hangovers at work are related to
      problems within the workplace and may lead to lowered productivity and morale.

PMID- 8979213
TI  - Cloninger's tridimensional theory of personality and psychopathology:
      applications to substance use disorders.
AB  - OBJECTIVE: To evaluate studies that applied Cloninger's tridimensional theory of
      personality to substance abusers. METHODS: Medline and PsychInfo data bases were
      searched for studies published between 1986 and mid-1995 that used the
      Tridimensional Personality Questionnaire (TPQ). A supplemental manual search was
      conducted to identify additional evaluations of the tridimensional theory.
      Reports were reviewed if they included substance abusers or related
      tridimensional traits to substance use measures. RESULTS: Factor analyses did not
      consistently support the tridimensionality of the TPQ. Novelty Seeking (NS)
      traits distinguished alcoholics from nonalcoholics, Type B and Type 2 alcoholics
      from their Type A and Type 1 counterparts, smokers from nonsmokers, and
      individuals (substance abusers and nonabusers) with and without antisocial
      personality disorder (ASPD). Tridimensional traits independently predicted early
      onset alcohol abuse and serious delinquency in studies that did not employ the
      TPQ and were significantly associated with concurrent substance abuse among
      adolescents. Most studies that compared nonalcoholic youth with positive and
      negative family histories of alcoholism reported nonsignificant TPQ differences
      or very small effects. Few alcoholics, cigarette smokers or sons of alcoholics
      displayed Type 1 (low novelty seeking, high harm avoidance, high reward
      dependence) or Type 2 (high novelty seeking, low harm avoidance, low reward
      dependence) TPQ profiles, but rarely were levels of tridimensional traits
      determined by reference to established norms. CONCLUSIONS: NS predicts early
      onset alcohol abuse and criminality and discriminates alcoholics exhibiting
      antisocial behavior and persons with ASPD from their nonantisocial counterparts.
      Findings for the Harm Avoidance (HA) and Reward Dependence TPQ subscales are much
      less consistent. Some support for the role of elevated HA in intensity of
      substance use has been adduced. At present, the utility of the TPQ for prevention
      or clinical purposes is not well established.

PMID- 8979214
TI  - Organization of psychological functions in alcoholics and nonalcoholics: a test
      of the compensatory hypothesis.
AB  - OBJECTIVE: We investigated the compensatory hypothesis that cognitive deficits in
      sober alcoholics would reveal differences in the organization of their cognitive
      structures or functions relative to nonalcoholic peers with no deficits. METHOD:
      Following the method of Tracy and Bates, who tested a similar hypothesis in light
      versus heavy social drinkers, we used structural equation modeling (SEM: LISREL)
      to test the compensatory hypothesis. Alcoholics (n = 131, 83 male) and peer
      nonalcoholics (n = 83, 47 male) were given tests of verbal, visual-spatial and
      abstracting/problem-solving skills. RESULTS: LISREL analyses indicated that the
      three factors (latent variables) representing the three skills and the loading of
      the tasks on these factors were invariant (i.e., similar) across groups. However,
      factor variances and covariances were noninvariant. Analyses identifying the
      sources of these differences revealed similarities between the heavy social
      drinkers of Tracy and Bates' study and our alcoholic sample. CONCLUSIONS: Results
      from the present study on cognitive organization in alcoholics, as well as our
      interpretation of Tracy and Bates' findings on the same in heavy social drinkers,
      support the notion of compensation and reorganization of cognitive function;
      however, other explanations cannot be ruled out.

PMID- 8979215
TI  - Sex ratios of drinking patterns and problems among blacks and whites: results
      from a national survey.
AB  - OBJECTIVE: The purpose of this study is to explore whether there are differences
      in sex ratios of drinking patterns and related problems among blacks and whites,
      and if so to explain these differences. METHOD: The study is based on a national
      survey including 1,947 (male, 723; female, 1,224) black and 1,777 (male, 743;
      female, 1,034) white men and women who were sampled from U.S. adult households
      using probability methods. Hierarchical regression methods were used to test
      whether there are significant racial differences in the sex ratio of drinking
      patterns and problems in the two racial groups. RESULTS: The findings showed that
      there were no substantive differences in drinking sex ratios along racial lines.
      However, white women were at the highest risk of experiencing alcohol-related
      problems as rates of heavier drinking increased, and the effects of heavier
      drinking differed much more among the sexes for whites than blacks. CONCLUSIONS:
      The findings for whites are consistent with previous research showing that, due
      to both biological and psychosocial factors, women when consuming the same
      amounts of alcohol as men may be at more risk for experiencing intoxication and
      alcohol-related problems. However, the findings for blacks, which show less
      problem vulnerability among women than men, have rarely been reported. It was
      suggested that the comparative risk of alcohol problems may be lower for black
      women due to possible physiological differences and differences in the normative
      climate of women's drinking in the two racial groups.

PMID- 8979216
TI  - Couple communication patterns of maritally aggressive and nonaggressive male
      alcoholics.
AB  - OBJECTIVE: This study was conducted to examine the associations between
      communication problems and marital violence in couples with a male alcoholic, and
      to determine whether the communication correlates of marital violence found in
      nonalcoholic community samples also characterize male alcoholics' relationships.
      METHOD: Ninety newly abstinent treatment-seeking male alcoholics and their wives
      completed a 10-minute problem discussion while both partners were sober. Their
      communication behaviors were coded with the Marital Interaction Coding system.
      Couples were separated into maritally aggressive (n = 60 couples) and
      nonaggressive (n = 30 couples) groups on the basis of any husband-to-wife
      physical aggression in the previous 12 months. RESULTS: The base-rate percentage
      of aversive-defensive communication was significantly higher for couples with a
      physically aggressive husband than for couples with a nonaggressive husband. The
      base-rate percentage of facilitative-enhancing communication did not differ
      significantly between groups. In sequential analyses, physically aggressive
      husbands, but not their wives, displayed more negative reciprocity than their
      nonaggressive counterparts. Alcoholic husbands in general displayed lower rates
      of facilitative-enhancing communication than did their wives. CONCLUSIONS:
      Husband-to-wife marital aggression was associated with problematic communication
      among couples with an alcoholic husband during a sober interaction in a
      laboratory setting, extending prior nonalcoholic community sample research to
      male alcoholics' relationships. The maritally aggressive alcoholics were high in
      negative responses contingent upon their wives' prior negative behavior, and were
      unlikely to terminate aversive interchanges. Communication problems may be
      important in understanding and treating co-occurring alcoholism and marital
      violence.

PMID- 8979217
TI  - Sexual satisfaction and dysfunction in marriages of male alcoholics: comparison
      with nonalcoholic maritally conflicted and nonconflicted couples.
AB  - OBJECTIVE: This study examined the contribution of alcoholism and marital
      conflict to male alcoholics' sexual problems. METHOD: Married couples with an
      alcoholic husband (n = 26) were compared with 26 maritally conflicted and 26
      nonconflicted couples without alcohol-related problems on both sexual dysfunction
      and sexual satisfaction. RESULTS: The male alcoholics and their wives experienced
      less sexual satisfaction across a range of variables and more sexual dysfunction
      specifically husbands' diminished sexual interest, impotence and premature
      ejaculation, and wives' painful intercourse-than nonconflicted couples. However,
      impotence was the only aspect on which alcoholics reported more difficulties than
      did maritally conflicted couples. When husbands' age was considered, more
      frequent retarded ejaculation with older age was unique to the alcoholics since
      it did not occur in conflicted or nonconflicted husbands; and there was a greater
      decline in frequency of intercourse with older age among the alcoholic than among
      the conflicted couples. CONCLUSIONS: These findings are consistent with a
      biopsychosocial formulation of alcoholics' sexual adjustment problems that
      implicates (1) marital conflict as a major contributing factor to most of these
      problems and (2) the combined role of both marital conflict and the physical
      effects of chronic alcohol abuse as most relevant to the elevated rates of
      impotence and retarded ejaculation (among older alcoholics) and the steeper
      decline in intercourse frequency with age.

PMID- 8979218
TI  - Drinking motives predict alcohol-related problems in college students.
AB  - OBJECTIVE: Drinking motives have frequently been linked to both the quantity of
      alcohol consumption and the likelihood of negative consequences. For motivational
      models of drinking to be useful, however, drinking motives must have predictive
      power independent of other variables typically associated with alcohol-related
      problems. Thus, this study evaluated the relationship between drinking motives
      and alcohol-related problems, after first accounting for high-risk alcohol
      consumption and gender, METHOD: Subjects were 139 male and female (61%) college
      undergraduates, who completed a battery of self-report questionnaires as part of
      a course requirement. RESULTS: Using hierarchical regression techniques, we found
      that the combination of maximum daily quantity and negative reinforcement reasons
      for drinking accounted for 61% of the variance on a measure of lifetime alcohol
      related problems. Contrary to earlier research, neither gender nor positive
      reinforcement motives were significant predictors in the complete model. Follow
      up analyses, conducted separately for negative and positive reinforcement
      motives, indicated that maximum daily quantity partially mediated the
      relationships between both types of motives and drinking problems; however, both
      positive and negative reinforcement motives retained unique predictive power.
      CONCLUSIONS: Motives operate both indirectly through heavy drinking and directly
      to account for drinking problems. Results support the utility of motivational
      models of alcohol use in understanding alcohol-related problems in college
      students.

PMID- 8979219
TI  - Diagnosis of mucin-producing tumor of the pancreas with an intraductal
      ultrasonographic system.
AB  - The purpose of this study is to examine the usefulness of intraductal
      ultrasonography at a frequency of 20 or 30 MHz in the diagnosis of mucin
      producing tumor. The subjects were 66 patients with mucin-producing tumor (10
      with main pancreatic duct type tumor and 56 with branch type tumor) who had also
      undergone endoscopic ultrasonography. In main pancreatic duct type tumors, we
      could diagnose the extent of the tumor and evaluate the invasion of the tumor
      into the pancreatic parenchyma in all seven patients who had undergone resection
      (three invasive tumors, four noninvasive tumors). Sixteen of 32 resected branch
      type tumors showing mural nodules with intraductal sonography were carcinoma or
      adenoma. On comparing intraductal and endoscopic ultrasonography in the rate of
      detecting nodules, in five tumors (one carcinoma and four adenomas), nodules were
      detected only with intraductal ultrasonography. In conclusion, intraductal
      ultrasonography is very useful for the diagnosis in the main pancreatic duct type
      tumor and in the detection of mural nodules in the branch type tumor.

PMID- 8979220
TI  - Value of laparoscopic ultrasonography in staging of proximal bile duct tumors.
AB  - The additional value of laparoscopic ultrasonography was evaluated prospectively
      in 35 patients undergoing diagnostic laparoscopy for a suspected potentially
      resectable proximal bile duct tumor. Findings were compared with transabdominal
      ultrasonography, laparoscopy, surgery, and pathology. Laparoscopic
      ultrasonography was able to visualize the presence and origin of small bile duct
      tumors or stones and small liver metastases, which could not be seen or could be
      visualized only doubtfully by ultrasonography and laparoscopy. Laparoscopic
      ultrasonography was more useful in staging of small tumors of the gallbladder or
      proximal common bile duct than in staging bifurcation (Klatskin) tumors.
      Additional information provided by laparoscopic ultrasonography led to a change
      in diagnosis or tumor stage in eight patients (23%) and to avoidance of
      laparotomy in three patients (9%).

PMID- 8979221
TI  - Growth retardation in fetuses with gastroschisis.
AB  - This study was designed to determine the prevalence of intrauterine growth
      restriction in neonates with gastroschisis and to evaluate the accuracy of the
      ultrasonographic diagnosis of intrauterine growth restriction. Birth weight and
      gestational age were determined for 46 infants diagnosed prenatally as having
      gastroschisis. Biometric data were analysed for the 30 pregnancies in which an
      examination was conducted within 1 week of delivery. Fetal growth parameters were
      compared with norms for gestational age. The prevalence of intrauterine growth
      restriction in the entire study group was 24% with a mean birth weight of 2401 +/
      508 g. Ultrasonographic estimated fetal weight was significantly less than birth
      weight (mean, 2079 +/- 508 g versus 2331 +/- 512 g, respectively; P < 0.0001).
      Intrauterine growth restriction was predicted in 43% of infants but was present
      in only 23%. The percentage difference between measured abdominal circumference
      and gestational age norm was significantly more than for biparietal diameter and
      for femur length (P < 0.001). Of the three biometric measures, only the
      difference between measured abdominal circumference and gestational age norms and
      the difference between estimated fetal weight and birth weight showed a
      significant correlation. Both abdominal circumference and femur length correlated
      with the difference between estimated fetal weight and birth weight. We conclude
      that the prevalence of intrauterine growth restriction is increased in infants
      with gastroschisis but is overestimated with prenatal ultrasonography, primarily
      because of smaller than average abdominal circumference measurements.

PMID- 8979222
TI  - Typical sonographic appearance of duodenal diverticulum.
AB  - During routine transabdominal ultrasonography of the hepatobiliary tract an
      occasional persistent bright linear or concave echo was detected that disrupted
      the normal images we routinely obtained of the pancreatic head. We began to
      suspect this echo to be the sonographic representation of a duodenal
      diverticulum. To confirm our suspicions we performed a prospective study. Over a
      20 month period, 30 consecutive patients with a sonographically suspected
      duodenal diverticulum were followed up with either an upper gastrointestinal
      series, gastroscopy, or, depending on the patient's clinical symptoms, endoscopic
      retrograde cholangiopancreaticography. One patient was examined with simultaneous
      fluoroscopy and ultrasonography. The results of these examinations were then
      compared to the respective ultrasonograms by a qualified radiologist and
      sonographer. The suspected duodenal diverticulum, detected primarily with
      ultrasonography, was confirmed with follow-up examinations in all 30 patients.
      The persistent echo detected sonographically had the same anatomic position as
      the diverticulum seen during fluoroscopy. We concluded that duodenal diverticulum
      located near the pancreatic head has a rather typical sonographic appearance.

PMID- 8979223
TI  - Sonographic prediction of viability in testicular torsion: preliminary
      observations.
AB  - This study was performed to determine if sonography can assist in predicting
      testicular viability in the setting of testicular torsion. Sixteen patients with
      sonographically diagnosed and surgically proved testicular torsion were studied.
      The preoperative sonograms were reviewed retrospectively to determine testicular
      echogenicity and homogeneity, testicular size and vascularity, scrotal skin
      thickness and vascularity, and the presence or absence of a hydrocele. These
      findings were correlated with the viability of the testis at surgery. All nine
      patients with normal homogeneous testicular echogenicity had viable testes at
      surgery. All seven patients with hypoechoic or inhomogeneous testes had nonviable
      testes at surgery and pathologic evidence of necrosis. The other findings were
      less helpful in predicting viability. In the setting of testicular torsion,
      normal testicular echogenicity is a strong predictor of viability. Immediate
      surgical detorsion in these patients carries a very high likelihood of salvaging
      the affected testis.

PMID- 8979224
TI  - Color Doppler imaging versus phlebography in the diagnosis of deep leg and pelvic
      vein thrombosis.
AB  - The objective of this prospective study was to evaluate the accuracy of color
      Doppler imaging in comparison to phlebography in diagnosing phlebothrombosis.
      Five hundred and twenty-six phlebographies (reference method) were compared with
      526 color Doppler sonographic examinations. Thrombosis diagnosed with color
      Doppler imaging showed a sensitivity of 98.0% (400 of 408). In 91.6% (482 of 526)
      of all examinations the extent of the thrombosis diagnosed with phlebography
      could also be seen with color Doppler imaging. When the clinical situation is
      unclear, color Doppler imaging should precede phlebography. Only when findings
      with ultrasonography are questionable should phlebography definitely be
      considered.

PMID- 8979225
TI  - Sonographic features of head and neck hemangiomas and vascular malformations:
      review of 23 patients.
AB  - The sonographic features of 23 head and neck hemangiomas and vascular
      malformations are presented. A focal mass lesion was seen in all patients. The
      predominant sonographic features were a well-defined hypoechoic mass lesion with
      heterogeneous echotexture and the presence of cystic and sinusoidal spaces
      within, as well as the occasional presence of phleboliths. Color Doppler imaging
      demonstrated flow in 12 of 13 lesions. When performing sonography on soft tissue
      masses in the head and neck, the presence of color Doppler signal in a well
      defined hypoechoic mass with heterogeneous echotexture should raise the
      possibility of an hemangioma.

PMID- 8979226
TI  - Ultrasonographic diagnosis of subclinical filariasis.
AB  - Asymptomatic persons with lymphatic filariasis may harbor microfiliariae in the
      circulation, and despite the lack of symptoms, these patients may have occult
      pathologic lesions and renal abnormalities. Earlier investigators have shown that
      it is possible to detect live adult filarial worms and dilation of lymphatic
      channels with ultrasonography. It is also possible to assess response to therapy.
      Using sonography, we detected twirling motions in dilated lymph channels and
      characteristic sonographic findings associated with presence of adult filariae.
      On follow-up examination we also found evidence of loss of worm activity after
      chemotherapy.

PMID- 8979227
TI  - Clinical utility of color Doppler sonography in the differentiation of
      hepatocellular carcinoma from metastases and hemangioma.
AB  - The clinical utility of color Doppler sonography in the differentiation of
      hepatocellular carcinoma from metastases and hemangioma was investigated in 72
      hepatocellular carcinomas (80 lesions), 30 metastases (82 lesions), and 39
      hemangiomas (54 lesions). Overlaps of color patterns were found among
      hepatocellular carcinoma, metastases and hemangioma. Pulsatile waves from lesions
      with the basket, vessels within tumor, or spot patterns, or lesions measuring
      less than 3 cm with detectable signals, did not favor the diagnosis of
      hemangioma. In conclusion, color Doppler sonography can aid in the
      differentiation of hepatocellular carcinoma from hemangioma but may be unreliable
      in the differentiation of hepatocellular carcinoma from hypervascular metastases.

PMID- 8979228
TI  - Increased cortical echogenicity of the normal kidney in infants with unilateral
      renal artery stenosis: report of two cases.

PMID- 8979229
TI  - Sonographic identification of perinatal testicular torsion.

PMID- 8979230
TI  - Antenatal diagnosis of Wilms tumor.

PMID- 8979231
TI  - Toward a political ecology of health in medical anthropology.

PMID- 8979232
TI  - The cultural debate over female circumcision: the Sudanese are arguing this one
      out for themselves.
AB  - This article critiques medical ecological analysis of female circumcision as a
      "maladaptive cultural pattern" and argues that this highly controversial
      procedure must be analyzed within the larger contexts of women's lives in
      underdeveloped countries. International efforts to eradicate female circumcision,
      while often couched in seemingly progressive feminist rhetoric, inadvertently
      serve to mask the negative health effects of the economic exploitation of poor
      countries such as Sudan. Reproductive histories and ethnographic data are used to
      argue that though female circumcision is not maladaptive, cultural discourse
      about it is resulting in changes in the meaning, techniques, and frequency of
      this practice.

PMID- 8979233
TI  - A biocultural perspective on health and household economy in southern Peru.
AB  - This article presents a biocultural approach to human health that integrates
      perspectives from anthropological political economy, ecology, and human
      adaptability. This approach frames local conditions in relation to
      macrohistorical forces, and focuses on the social relations that underlie health
      and responses to illness. It examines the coping responses of human agents
      operating with a "conditional rationality," and the multiple consequences to
      these responses. The approach is illustrated with results from a study on the
      relationship between health and household economy among small-scale farmers of
      the Nunoa District in the southern Peruvian Andes. Poor health and nutritional
      status reflect historical and current economic conditions in the district.
      Households in illness plant half as many fields at twice the labor cost as
      healthy households. Among poor households the effects of illness on farming
      production are exacerbated by their inability to adequately supplement family
      labor with nonhousehold workers. The consequences of illness can force changes in
      access to resources and production strategies, thus shaping household health and
      economy in the future.

PMID- 8979235
TI  - More than dialogue: contributions to the recapturing of anthropology.

PMID- 8979234
TI  - Farewell to adaptationism: unnatural selection and the politics of biology.
AB  - This article argues that human adaptation has lost its utility as a conceptual
      tool for either biological or medical anthropology, despite the recent efforts of
      practitioners in these subdisciplines to rescue it by considering the influences
      of power, history, and global social processes. It draws on cases from diverse
      fields, including evolutionary studies, ethology, genetics, and epidemiology, to
      suggest new ways of conceptualizing the relationship between humans and their
      physical and biotic environments; environments that they, and to a lesser degree
      other species, are not so much "adapting to" as transforming, while being
      transformed themselves in the process. Central to this reconceptualization is an
      understanding of human behavior and environmental relationships in political
      economic context.

PMID- 8979236
TI  - Should medical ecology be political?

PMID- 8979237
TI  - Reconfiguring nature and culture: intersections of medical anthropology and
      technoscience studies.

PMID- 8979239
TI  - New bottles, old wine: hidden cultural assumptions in a computerized explanation
      system for migraine sufferers.
AB  - Sophisticated computer programs known as "intelligent systems" have been
      developed for use in medical settings for over two decades. Such systems
      explicitly encode information about task domains, problem attributes, and problem
      solving strategies. They also embody tacit assumptions held by those who build
      them, reflecting meanings taken for granted in particular cultural and
      disciplinary arenas. This article examines assumptions built into the design of a
      patient education system for migraine sufferers, drawing upon extended
      participant-observation of the development process. Its designers view the system
      as neutral, but observation reveals that it embodies a physician's point of view.
      While intended to support migraine patients by offering useful information not
      given them by physicians, the system in fact offers information characterized by
      the same assumptions and deletions as that provided by neurologists. Thus,
      although intended to empower migraine patients, this system may actually
      reinforce rather than reduce the power differential between doctor and patient.

PMID- 8979238
TI  - The social dynamics of genetic testing: the case of Fragile-X.
AB  - This article considers a program to screen school children for Fragile-X Syndrome
      as a way to explore several features of the growing practice of genetic testing
      in American society. These include the common practice of predictive testing in
      nonclinical settings; the economic, entrepreneurial, and policy interests that
      are driving the development of genetic screening programs; and the public support
      for genetic testing even when there are no effective therapeutic interventions.
      Drawing from research on popular images of genetics, I argue that cultural
      beliefs and expectations, widely conveyed through popular narratives, are
      encouraging the search for diagnostic information and enhancing the appeal of
      genetic explanations for a growing range of conditions.

PMID- 8979240
TI  - Death in technological time: locating the end of meaningful life.
AB  - This article demonstrates how debate about technologically manipulated death is
      elaborated in radically different forms in the scientifically sophisticated
      spaces of Japan and North America. Using recent historical materials and
      contemporary medical, philosophical, and media publications, I argue that the
      institutionalization and legitimization of "brain death" as the end of life in
      North America have been justified by a dominant discourse in which it is asserted
      that if certain measurable criteria are fulfilled, an individual can be declared
      scientifically dead. In Japan, by contrast, death is interpreted primarily as a
      social and not an individual event, and efforts to scientifically define the end
      of life as a measurable point in time are rejected outright by the majority,
      including many clinicians. The margins between nature and culture are debated in
      both cultural spaces, but assigned different moral status in the respective
      dominant discourse.

PMID- 8979241
TI  - From simple technology to complex arena: classification of Pap smears, 1917-90.
AB  - This article explores historical constructions of Pap smear classification
      systems from 1917 to 1990. Using a social worlds/arenas analysis, we examine the
      perspectives and properties of all the major actors (both human and nonhuman) in
      the Pap smear arena, including implicated actors. Analytical emphasis is on
      interpretive struggles among different actors in this arena and centers on the
      consequences of such conflicts for global classificatory systems and on the
      global classificatory criteria. We describe some of the local clinical "work
      arounds" designed to resolve problems of classification standards in practice. In
      drawing theoretical conclusions, comparison is made between Pap smear
      classification systems and two other systems.

PMID- 8979242
TI  - "How's the baby doing?" Struggling with narratives of progress in a neonatal
      intensive care unit.
AB  - In this at once biographical and autobiographical piece (cf. Shapiro 1988), I
      describe the processes of "knowledge-making" of one neonatal intensive care
      parent. In particular, I investigate the ways that narratives of linear progress
      informed my efforts to understand my son's condition and future prospects, that
      is, to engage in lay prognostication. In examining and comparing the three
      metaphors most commonly used to describe my son's changing condition-roller
      coaster, graduation, and course-I explore how the discrepancy between narratives
      of linear progress and the complex and volatile condition of many premature
      and/or critically ill babies is discursively managed in a neonatal intensive care
      unit.

PMID- 8979243
TI  - Technology and alternative cancer therapies: an analysis of heterodoxy and
      constructivism.
AB  - Theories of the construction of technology are reviewed from the wider
      interdisciplinary conversation known as science and technology studies (STS) and
      from the growing field of the anthropology of science and technology. These
      theories are used to contribute to research situated at the intersection of the
      anthropology of alternative medicine and of medical technologies. Cases drawn
      from the research tradition on microbial theories of cancer are considered to
      show how unorthodox medical theories become embedded in technologies through
      choices in microscope design and treatment technologies. In turn, the
      technologies contribute to the heterodox standing of the researchers, their
      research, and their therapies.

PMID- 8979244
TI  - Transforming "body parts" into therapeutic tools: a report from Germany.

PMID- 8979245
TI  - An excellent prognosis.

PMID- 8979246
TI  - Anthropology and technoscience studies: prospects for synthesis and ambiguity.

PMID- 8979247
TI  - Small molecule ligands for oxytocin and vasopressin receptors.

PMID- 8979248
TI  - Inhibitors of endothelin.
AB  - With the advent of the first generation of both selective and nonselective
      endothelin antagonists being a relatively recent event, the manifold therapeutic
      potentials of these compounds are only now being explored clinically.
      Undoubtedly, numerous clinical utilities for these compounds will soon be
      realized.

PMID- 8979249
TI  - Structural modifications of glycopeptide antibiotics.

PMID- 8979250
TI  - The 13C isotope and nuclear magnetic resonance: unique tools for the study of
      brain metabolism.
AB  - As studies of brain metabolism grow in complexity, investigators turn
      increasingly to nuclear magnetic resonance spectroscopy combined with 13C
      isotopic labeling. The unique ability to detect labeling non-destructively in
      specific carbon positions of individual compounds has opened the way to
      investigate brain metabolism in systems ranging from cellular preparations to the
      human brain in vivo. This review is written for investigators whose backgrounds
      do not include detailed knowledge of principles of nuclear magnetic resonance.
      Its purpose is to show the wide array of NMR techniques for 13C detection that
      are available for application in different systems to study aspects of brain
      metabolism, such as metabolic compartmentation and measurements of the
      tricarboxylic acid cycle rate in vivo. Basic NMR concepts are explained, and,
      because each detection method possesses specific advantages to address the
      requirements of different experimental goals, basic explanations and examples are
      given for each technique. The review should provide readers with a basic
      understanding of the methods of 13C detection by NMR and assess which of the
      methods are most applicable to the particular issues they may face in their own
      research.

PMID- 8979251
TI  - Diagnostic tools for the detection of subclinical hepatic encephalopathy:
      comparison of standard and computerized psychometric tests with spectral-EEG.
AB  - The prevalence of subclinical hepatic encephalopathy (SHE) varies according to
      the diagnostic tool used in its detection. Since a standardised approach to the
      diagnosis of SHE is not yet available, we compared psychometric tests and EEG
      spectral analysis. On the same day 32 cirrhotic patients without overt hepatic
      encephalopathy and 18 controls were assessed by psychometric tests, both standard
      and computerized (CPT), and by EEG spectral analysis (EEG-SA). The CPT, measuring
      reaction time (Rt) and errors (er), were Font, Choice1, Choice2 and Scan test.
      The standard psychometric tests were the number connection test (NCT), the Reitan
      B test, the Line Tracing Test [for time: LTT(t) and for errors: LTT(er)], and the
      Symbol Digit test (SD). Both psychometric tests [Reitan-B test, LTT(er) and CPT
      but Font (Rt) and Choice2 (er)] and EEG-SA parameters [mean dominant frequency
      (MDF) and theta power (theta %)] significantly correlated (p < 0.05) with albumin
      plasma levels. LTT(er), Scan, Font, Choice1 and Choice2 were significantly
      related to theta % and MDF. There was no control with positive EEG-SA, though one
      control was positive with LTT(t) and with the number of errors made during Font
      and Scan tests. The percentage of cirrhotics with positive EEG-SA was 34% (CI95%
      = 19-53), while 9-66% were positive with psychometric tests, depending on the
      test considered. In spite of the correlation between neuropsychological and
      neurophysiological parameters, the diagnostic agreement between EEG-SA and each
      psychometric test was not high. IN CONCLUSION: 1) neurophysiological and
      neuropsychological impairment in cirrhotics without overt hepatic encephalopathy
      were found linked to each other and to hepatic dysfunction; 2) psychometric tests
      were not sufficiently good predictors of EEG alterations; therefore,
      neuropsychological tools can not substitute neurophysiological ones to detect CNS
      dysfunction in liver disease.

PMID- 8979252
TI  - Flumazenil does not affect the increase in rat hippocampal extracellular
      glutamate concentration produced during thioacetamide-induced hepatic
      encephalopathy.
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric disorder that often occurs as a
      consequence of acute or chronic liver failure. Previous reports have suggested
      that alterations in amino acid neurotransmission, particularly glutamate, may
      play an important role in the pathogenesis of HE. The objectives of the present
      study were to test the hypothesis that extracellular glutamate concentration is
      increased during HE, and to determine if flumazenil, a benzodiazepine antagonist,
      alters the extracellular concentration of glutamate during HE. The experimental
      approach involved using microdialysis probes to measure rat hippocampal
      extracellular glutamate concentration. HE was brought about as a result of
      thioacetamide-induced liver failure. Thioacetamide produced behavioral and
      metabolic effects, such as somnolence, hyperventilation and hyperammonemia,
      consistent with stage three HE. Comparison with saline-treated rats demonstrated
      that HE was associated with a significant increase (p = 0.010) in extracellular
      hippocampal glutamate concentration. Administration of flumazenil caused a
      transient increase in arousal level, but did not affect the increase in glutamate
      concentration (p = 0.93). These results corroborate the theory that glutamate
      neurotransmission is altered during HE and suggest that the flumazenil arousal of
      HE rats is not mediated by a change in extracellular glutamate concentration.

PMID- 8979253
TI  - Effects of ethanol on GLUT1 protein and gene expression in rat astrocytes.
AB  - Effects of ethanol on glucose transporter gene expression were examined in
      cultured rat astrocytes. Exposure to 50 or 100 mM ethanol for 18 hours
      significantly inhibited hexose uptake and reduced the number of glucose
      transporters, as indicated by binding studies with cytochalasin B. Indirect
      immunofluorescence and immunoperoxidase staining showed marked reduction of the
      GLUT1 glucose transporter by exposure to 100 mM ethanol for 5 or 18 hours, but no
      obvious change in response to 50 mM ethanol. Western blot analysis showed GLUT1
      protein levels to be decreased by 52 +/- 12% (p < 0.05) after exposure to 100 mM
      ethanol for 18 hours. In situ hybridization histochemistry indicated an increase
      in steady-state GLUT1 mRNA in astrocytes exposed to 50 or 100 mM ethanol for 5 or
      18 hours. Quantitation of GLUT1 mRNA levels by northern blot analysis showed that
      GLUT1 mRNA levels were increased by 59 and 112% in cells treated for 5 h with 50
      and 100 mM ethanol, respectively. A similar effect was observed after treatment
      for 18 hours, but ethanol did not alter actin gene expression. Experiments using
      actinomycin D to block RNA synthesis suggest that this increase in steady-state
      mRNA level results from increased message stability. These results suggest that
      ethanol acts on GLUT1 gene expression at the post-transcriptional level.

PMID- 8979254
TI  - Cerebral hypoxia-ischemia increases microsomal iron in newborn piglets.
AB  - The primary cause of neurologic impairment in newborn infants is hypoxic-ischemic
      injury. Studies of the mechanisms involved in the damaging effects of hypoxia
      ischemia and reperfusion in brain tissue indicate significant contributions from
      reactive oxygen species, with the loss of homeostatic control of intracellular
      iron an important determinant of oxidant-mediated damage. We investigated the
      effects of cerebral hypoxia-ischemia and reperfusion on the redistribution of
      nonheme iron in newborn piglets. Anesthetized newborn piglets were subjected to
      reductions in cerebral blood flow by phlebotomy and cervical cuff compression.
      Control animals were sham-operated. Subcellular fractions were isolated from
      brain tissue homogenates by differential centrifugation, and nonheme iron
      contents of these fractions were measured with ferene-S. Iron contents in the
      homogenates were not altered. However, iron contents of the microsomal fractions
      of animals subjected to 30 minutes of hypoxia-ischemia increased from 0.517 +/-
      0.053 to 0.930 +/- 0.061 nmol/mg protein (p < 0.01); 120 minutes of reperfusion
      caused no further changes. This translocation of iron may be linked to oxidative
      alterations of brain proteins, which we investigated by detection of
      dinitrophenylhydrazine-derivitized protein carbonyls, which are characteristic of
      iron-catalyzed oxidation reactions.

PMID- 8979255
TI  - Long-term changes in glial fibrillary acidic protein and glutamine synthetase
      immunoreactivities in the supraoptic nucleus of portacaval shunted rats.
AB  - The present study was undertaken to ascertain whether, and to what extent, glial
      fibrillary acidic protein (GFAP) and glutamine synthetase (GS) expressions in the
      supraoptic nucleus (SON) could be modulated after one month and six months of
      portacaval shunting (PCS) in rats. GFAP and GS immunoreactivities were
      significantly higher in PCS rats than in control rats at one and six months. The
      increased GFAP and GS immunoreactivities observed in the SON astrocytes were
      directly related to the duration of PCS. In PCS rats, the number and length of
      both GFAP and GS immunopositive astroglial processes increased not only in the
      hypothalamic nucleus but in the perinuclear zone, where glutamatergic pathways
      have been described, whereas GFAP and GS expressions decreased in the ventral
      glial lamina. Since GS is one of the glutamate metabolizing enzymes and the SON
      is one of the areas of glutamatergic activity, our results show that astrocytes
      respond differentially to glutamate toxicity. This suggests that overexpression
      of GFAP and GS immunoreactivities could be associated with glutamatergic
      neurotransmission disorders.

PMID- 8979256
TI  - Omega-3 fatty acids and the peroxisome.
AB  - The interactions between the omega-3 unsaturated fatty acids and peroxisomal
      function have been reviewed, in order to update and integrate knowledge in this
      area. Following a brief retrospective of the major clinical involvements of these
      fatty acids, the participation of the peroxisome in their metabolism has been
      appraised-the peroxisome being shown to exert a major influence on both the
      synthesis and degradation of the omega-3 fatty acids, with these effects flowing
      on to the widespread physiological implications of the derivative eicosanoids.
      Interactions between the omega-3 and omega-6 families of fatty acids have been
      discussed, as have the interdependent phenomena of peroxisome proliferation,
      membrane remodelling and cellular signalling. Amongst the signalling involvements
      covered were those of steroid hormone receptor superfamily, the
      phosphatidylcholine cycle, and the regulatory influences of oxygen free radicals.
      Comment has also been included on the separate biological roles of the individual
      omega-3 fatty acids, their influence on differential gene function, and on the
      molecular mechanisms of their pharmacological effects. It is concluded that the
      peroxisome is intimately involved in directing the metabolism and physiological
      influence of the omega-3 unsaturated fatty acids, and that this organelle merits
      much greater emphasis in future research aimed at unravelling the profound
      biological effects of these unique and multipotent compounds.

PMID- 8979257
TI  - Purification of carnitine acetyltransferase from skeletal muscle of the camel
      (Camelus dromedarius).
AB  - The enzyme carnitine acetyltransferase (CAT) catalyzes the reversible transfer of
      short-chain acyl groups between coenzyme A and L-carnitine, and hence, plays an
      important role in the beta-oxidation of fatty acids. Purification and
      characterization of CAT from desert animal species may help in explaining the
      involvement of secondary pathways for energy production in these species. In this
      paper, we report the purification and partial characterization of CAT from the
      Arabian camel. CAT was purified from the skeletal muscle of the Arabian camel by
      ammonium sulfate and acetone fractionation, followed by chromatography on DEAE
      Sepharose, agarose-Co A and Superose 12 gel filtration columns. CAT was purified
      by 2937-fold to a specific activity of 94 Units mg-1. The purified CAT was a
      monomer of 59 kDa as judged by native and SDS-PAGE, and showed a pI of 5.2. The
      enzyme displayed maximum activity with propionyl-Co A. Apparent Km for acetyl-,
      propionyl- and butyryl-Co A were 27.7, 17.3 and 29 microM respectively, while
      palmitoyl-Co A was not a substrate.

PMID- 8979258
TI  - Glycosylation is critical for natriuretic peptide receptor-B function.
AB  - Co-transfection of a truncated natriuretic peptide receptor-B (NPR-B) with the
      full length receptor results in a decrease of 60-80% in wild-type receptor
      activity. This reduction correlates with a loss of glycosylation of the full
      length NPR-B. This effect is dose-dependent, and occurs with no change in the
      glycosylation of the truncated receptor. Co-transfection of the full length NPR-B
      with other receptors yields similar results. These data suggest that
      glycosylation may be crucial for NPR-B function. Cross-linking studies further
      demonstrate that only fully glycosylated NPR-B receptors are able to bind ligand.
      Our data therefore argue that carbohydrate modification may be critical for NPR-B
      receptor ligand binding.

PMID- 8979259
TI  - Phosphorylation and activation of the intestinal guanylyl cyclase receptor for
      Escherichia coli heat-stable toxin by protein kinase C.
AB  - The heat-stable enterotoxin STa of E. coli causes diarrhea by binding to and
      stimulating intestinal membrane-bound guanylyl cyclase, triggering production of
      cyclic GMP. Agents which stimulate protein kinase C (PKC), including phorbol
      esters, synergistically enhance STa effects on cGMP and secretion. We
      investigated whether PKC causes phosphorylation of the STa receptor in vivo and
      in vitro. Immunoprecipitation of the STa receptor-guanylyl cyclase was carried
      out from extracts of T84 colon cells metabolically labelled with [32P]-phosphate
      using polyclonal anti-STa receptor antibody. The STa receptor was phosphorylated
      in its basal state, and 32P content in the 150 kDa holoreceptor band increased 2
      fold in cells exposed to phorbol ester for 1 h. In vitro, immunopurified STa
      receptor was readily phosphorylated by purified rat brain PKC. Phosphorylation
      was inhibited 40% by 5 microM of a synthetic peptide corresponding to the
      sequence around Ser1029 of the STa receptor, a site previously proposed as a
      potential PKC phosphorylation site. Treatment of the immunopurified STaR/GC with
      purified PKC increased STa-stimulated guanylyl cyclase activity 2-fold. We
      conclude that PKC phosphorylates and activates the STa receptor/guanylyl cyclase
      in vitro and in vivo; Ser1029 of the STaR/GC remains a candidate phosphorylation
      site by PKC.

PMID- 8979260
TI  - Vitamin A inhibits lipoperoxidation ascorbate-Fe++ dependent of rat kidney
      microsomes and mitochondria.
AB  - In the present study it was investigated if Vitamin A supplementation could
      protect rat kidney microsomes and mitochondria from in vitro lipoperoxidation.
      After incubation of rat kidney microsomes and mitochondria in an ascorbate-Fe+2
      system, at 37 degrees C during 60 min, it was observed that the total cpm/mg
      protein originated from light emission (chemiluminescence) was lower in those
      organelles obtained from the control group when compared with the vitamin A
      supplemented group. The fatty acid composition of microsomes and mitochondria
      from control group was profoundly modified when subjected to non-enzymatic
      lipoperoxidation with a considerable decrease of arachidonic acid, C20:4 (n-6)
      and docosapentaenoic acid, C22:5 (n-3) in mitochondria and docosahexaenoic acid
      C22:6 (n-3) in microsomes. As a consequence the peroxidizability index, a
      parameter based on the maximal rate of oxidation of specific fatty acids was
      higher in the supplemented animals than in those used as control. These results
      indicate that Vitamin A may act as antioxidant protecting rat kidney microsomes
      and mitochondria from deleterious effect.

PMID- 8979261
TI  - Heart FoF1-ATPase changes during the acute phase of Trypanosoma cruzi infection
      in rats.
AB  - The kinetic properties of ATP hydrolysis and synthesis by FoF1-ATPase of heart
      mitochondria were evaluated during the acute phase of T. cruzi infection in rats.
      Mitochondria and submitochondrial particles were isolated 7 days (early stage)
      and 25 days (late stage) following infection of rats with 2 x 10(5)
      trypomastigote forms of the Y strain of T. cruzi. The kinetic properties for ATP
      hydrolysis were altered for the early but not the late stage, showing a changed
      pH profile, increased K0.5 values, and a decreased total Vmax. The Arrhenius'
      plot for membrane-associated enzyme showed a higher transition temperature with a
      lower value for the activation energy in body temperature. For the Triton X-100
      solubilized enzyme, the plot was similar to the control. A decrease in the
      efficiency of ADP phosphorylation by mitochondria, measured by the firefly
      luciferase luminescence, was observed only during the late stage and appeared to
      be correlated with a decrease in the affinity of the FoF1-ATPase for ADP. It is
      proposed that in the early stage, during the acute phase of T. cruzi infection in
      rats, heart FoF1-ATPase undergoes a membrane-dependent conformational change in
      order to maintain the phosphorylation potential of mitochondria, which would
      compensate for the uncoupling of mitochondrial function. Also, during both the
      early and late stages, the enzyme seems to be under the regulation of the
      endogenous inhibitor protein for the preservation of cellular ATP levels.

PMID- 8979263
TI  - The 5' end sequences and exon organization in rat regucalcin gene.
AB  - The 5'-flanking region of the gene for a Ca(2+)-binding protein regucalcin was
      cloned from a rat genomic library which was constructed in lambda EMBL3 SP6/T7
      vector. The genomic library was screened by using the radiolabeled probe with the
      5' region (0.5 kb) of rat regucalcin complementary deoxyribonucleic acid (cDNA).
      Positive clone had the 5.5 kb fragment which was hybridized with the 5'-probe.
      This fragment contained three exons (I-III) of the gene coding for a rat
      regucalcin. The nucleotide sequence of exons completely agreed with that of a rat
      regucalcin cDNA clone. A supposed translational initiation site existed in the
      exon II. Homology analysis showed that a putative transcription start site in the
      rat regucalcin gene was located at position 26 downstream from a TATA-box.
      Another upstream element, a CCAAT box-like sequence, was located at -170.
      Moreover, there were many regulatory elements (Hox, AP-1, AP-2 and AP-4) in the
      5'-flanking region of the rat regucalcin gene. The organization of rat regucalcin
      gene seemed to be about 18 kb in size and consisted of seven exons and six
      introns.

PMID- 8979262
TI  - The relationship between altered membrane composition, eicosanoids and TNF
      induced IL1 and IL6 production in macrophages of rats fed fats of different
      unsaturated fatty acid composition.
AB  - The study investigated the changes in individual molecular species in PE and the
      effects of a variety of dietary fats with varying proportions of saturated and
      unsaturated fatty acids on membrane composition, eicosanoid production and
      cytokine production in thioglycollate-elicited rat macrophages. The data obtained
      indicates that the greatest degree of modulation by dietary fats on cytokine
      production was observed after 8 weeks feeding and at this time, the total diacyl
      species containing linoleic acid (18:2 n-6) and arachidonic acid (20:4 n-6) at
      the sn-2 position related in a curvilinear fashion to total 18:2 n-6 intake and
      that IL1 and IL6 production related in a curvilinear fashion to the total diacyl
      species with 20:4 and 18:2 at the sn-2 position. After 4 weeks of feeding, fish
      and olive oils enhanced production of IL6 and LTB4, however, while IL1
      production, after 8 weeks of dietary treatment, was greatest from macrophages of
      animals fed corn and olive oils, PGE2 production was greatest in the former group
      and LTB4 production in the latter. Thus an eicosanoid effect may explain the
      modulatory influence of olive oil and IL1 production but, cannot explain the
      effect of corn oil on production of the cytokine. The data from the present study
      provides some insight into how dietary fats could provide therapy for conditions
      in which inflammatory cytokines are implicated.

PMID- 8979264
TI  - Identification of seven novel mutations in LH beta-subunit gene by SSCP.
AB  - Seven new point mutations have been identified from LH beta-subunit gene by PCR
      mediated SSCP, and sequencing. One mutation was found changing amino acid from
      Gln102 to Ser102. The remaining six mutations, which did not change the codings,
      were in complete linkage disequilibrium. SSCP can be used in the diagnosis of LH
      related disorders.

PMID- 8979265
TI  - Structure and analysis of the mouse Na+/H+ exchanger (NHE1) gene: homology and
      conservation of splice sites.
AB  - The Na+/H+ exchanger is a widely distributed integral membrane protein that is
      responsible for pH regulation in mammalian tissues. We have cloned and analyzed
      the NHE1 isoform of the mouse genomic Na+/H+ exchanger. A clone from a mouse
      genomic library contained the NHE1 promoter region and the 5'-untranslated
      region. It also contained the first 121 amino acids of the coding region of the
      Na+/H+ exchanger. A splice site occurred after amino acid 121, at the same region
      as in the human NHE1 gene. The deduced amino terminal coding sequence was 76 and
      88% identical to the human and rat NHE1 sequences respectively. The 5'
      untranslated region was highly homologous to that of other species and two
      minicistrons contained in the human Na+/H+ exchanger were present in the mouse
      sequence. The results show that the deduced protein sequence of the mouse NHE1
      gene has a high level of homology with other species and that the splice site of
      the first intron is conserved. These results suggest that the first large intron
      may play an important role in the NHE1 gene expression.

PMID- 8979266
TI  - Effects of Schisandrin B and alpha-tocopherol on lipid peroxidation, in vitro and
      in vivo.
AB  - Effects of Schisandrin B (Sch B) and alpha-tocopherol (alpha-TOC) on ferric
      chloride (Fe3+) induced oxidation of erythrocyte membrane lipids in vitro and
      carbon tetrachloride (CCl4) induced lipid peroxidation in vivo were examined.
      While alpha-TOC could produce prooxidant and antioxidant effect on Fe(3+)-induced
      lipid peroxidation, Sch B only inhibited the peroxidation reaction. Pretreatment
      with alpha-TOC (3 mmol/kg/day x 3) did not protect against CCl4-induced lipid
      peroxidation and hepatocellular damage in mice, whereas Sch B pretreatment (0.3
      mmol/3.0 mmol/kg/day x 3) produced a dose-dependent protective effect on the CCl4
      induced hepatotoxicity. The ensemble of results suggests that the ability of Sch
      B to inhibit lipid peroxidation, while in the absence of pro-oxidant activity,
      may at least in part contribute to its hepatoprotective action.

PMID- 8979267
TI  - Inhibition of tumor invasion and metastasis by peptidic mimetics of Arg-Gly Asp
      (RGD) derived from the cell recognition site of fibronectin.
AB  - The partially modified retro- and retro-inverso peptides of the Arg-Gly Asp (RGD)
      sequence of fibronectin, in which the direction of the Arg residue is reversed
      and/or the chirality of the amino acid residue is inverted, i.e., mainly R(rev)
      COCH2CO-D and DR(rev)-COCH2CO-D, have been synthesized to examine their
      antimetastatic effects in murine lung or liver metastasis models, as well as
      their inhibitory effect on tumor cell invasion in vitro. R(rev)-COCH2CO-D
      inhibited lung metastasis produced by i.v. coinjection with B16-BL6 melanoma more
      potently than did other pseudo-peptides or the original RGDS peptide. Rrev
      COCH2CO-D also showed antimetastatic effects against several different types of
      tumor cells such as B16-BL6 melanoma, Colon26 M3.1 carcinoma, and L5178Y-ML25
      lymphoma cells, in a dose-dependent manner, and multiple administrations had a
      therapeutic effect on spontaneous lung metastasis. The invasion of melanoma cells
      into reconstituted basement membrane Matrigel in vitro was suppressed by R(rev)
      COCH2CO-D more effectively than by RGDS. These results indicate that the
      antimetastatic effect by R(rev)-COCH2CO-D was in part due to the inhibition of
      tumor invasion. The RGDS peptide decomposed when incubated with fresh plasma in
      vitro, whereas R(rev)-COCH2CO-D was not affected by this treatment. Thus, the
      reversion of the Arg-Gly linkage in the RGD sequence resulted in protease
      resistance leading to the retardation of the clearance of the peptide in vivo,
      and consequently augmented its antimetastatic and antiinvasive properties.
      Designed peptide analogues may provide various advantages and be useful for
      preventing cancer metastasis.

PMID- 8979268
TI  - The amino terminus of Cdk2 binds p21.
AB  - The cyclin-dependent kinase (Cdk) inhibitor known as p21, which is
      transcriptionally regulated by p53, can induce G1 arrest when overexpressed and
      inhibit the kinase activity of a wide variety of cyclin-Cdk complexes. Previous
      studies have demonstrated that a portion of the conserved region of p21 (amino
      acids 46-78), which is homologous to similar regions in the related Cdk
      inhibitors p27 and p57, can bind to Cdk2, and that this region is essential for
      kinase inhibition. However, the site(s) on Cdk2 that are involved in p21 binding
      have not been identified. We therefore created mutant Cdk2 molecules with various
      N-terminal and C-terminal deletions and tested each for their ability to bind to
      p21 by the yeast two-hybrid and the double-tagging assays. None of the deletion
      mutants tested bound to p21 by either assay. We next tested whether p21 could
      bind to Cdk7, a component of the cyclin-activating kinase complex. By both the
      double-tagging and yeast two-hybrid assays, p21 failed to bind to this protein,
      consistent with previous reports. However, hybrid molecules consisting of the
      amino-terminal half of Cdk2 and the carboxy-terminal half of Cdk7 (Cdk2/Cdk7)
      could bind to p21 by both assays, whereas the Cdk7/Cdk2 hybrids could not.
      Furthermore, the yeast Cdc28 protein, which is 65% identical with Cdk2, failed to
      bind to p21 by both the yeast two-hybrid and double-tagging assays. Cdk2/Cdc28
      hybrids but not Cdc28/Cdk2 hybrids could bind to p21. These results suggest that
      the amino-terminal half of Cdk2 is important for p21 binding, consistent with the
      recently published crystal-lographic data. Our data also suggest that the three
      dimensional structure of Cdk2 is likely altered by creating deletion mutants from
      either the amino- or carboxy-terminal end of the protein. Finally, we have
      mutated the Cdc28/Cdk2 hybrid protein and isolated several mutants, which are
      able to bind to p21. This approach may be useful for identifying residues in Cdk2
      and Cdc28 that affect their ability to bind to p21 and complement the
      crystallographic data.

PMID- 8979269
TI  - Clonal variation of p53 expression and proliferative phenotype in A253 squamous
      carcinoma cells.
AB  - Loss of normal p53 tumor-suppressor gene function is characteristic of the
      majority of squamous carcinomas. During the course of gene transfer studies in
      the human squamous carcinoma cell line, A253, which does not express p53 mRNA or
      protein, we incidentally observed increased levels of p53 expression in up to 20%
      of clonal cell lines derived from parental A253 cells. p 53-expressing A253 cells
      (A253-p53) were also isolated by dilutional cloning. Nuclear p53 protein was
      identified by immunohistochemistry in A253-p53 cells in a wild-type pattern, and
      p53 mRNA (2.5 kb) was demonstrated by northern blot. Mutational analysis of the
      p53 gene in A253-p53 cells revealed no evidence for mutations in exons 5-9. A253
      p53 cells could be distinguished from native A253 cells by prolonged doubling
      times (2-5 fold) and by a marked reduction of [3H]-thymidine uptake. Whereas A253
      cells were unresponsive to the growth-inhibitory effects of TGF-beta, EGF
      stimulated A253-p53 cells responded to TGF-beta with markedly reduced DNA
      synthetic rates. A253-p53 cells cocultured with A253 demonstrated enhanced cell
      growth and DNA synthesis rates compared to control A253-p53 cells. Finally, A253
      p53 cells show reduced expression of c-fos, fibronectin, thrombospondin and
      parathyroid hormone-related protein (PTHrP) mRNAs. PTHrP measured by RIA in
      conditioned medium was approximately 300 pM for A253 but undetectable for A253
      p53. We conclude that the A253 cell line contains a subpopulation of cells which
      express high levels of "wild-type-like" p53 protein. This results in dramatic
      changes in gene expression and a slower-growing phenotype in vitro.

PMID- 8979270
TI  - Combinatorial effects of monoclonal anti-p120 antibody (MAbp120), liposomes and
      hyperthermia on MCF-7 and LOX tumor cell lines.
AB  - The human nucleolar protein p120 is highly expressed in human cancers. Its high
      expression in breast cancer correlates with a poor prognosis, and its
      overexpression in 3T3 mouse fibroblasts causes malignant transformation. This
      study reports that a combination of monoclonal anti-p 120 antibody (MAbp120),
      liposomes (Lipo), and hyperthermia (HT) resulted in enhanced antitumor effects in
      cultured human breast adenocarcinoma (MCF-7) and human amelanotic melanoma (LOX)
      cells. Monoclonal antibody uptake and intracellular localization of the protein
      p120 were monitored by double labeling indirect immunofluorescence. Cell growth
      inhibition by the combination of MAbp120 + Lipo + HT was 65% for MCF-7 cells and
      96% for LOX cells. When tested on LOX cells, monoclonal antibodies (MAbB23,
      MAbC23) to other nucleolar proteins (B23, C23) produced only slight cytotoxicity
      with similar treatment protocols.

PMID- 8979272
TI  - Reference listings in cancer research.

PMID- 8979271
TI  - Effect of a tobacco-related nitrosamine on intercellular communication in human
      urothelial cells: a possible factor in smoking-related bladder carcinogenesis.
AB  - Bladder cancer is associated with smoking. Among the tobacco-derived carcinogens
      suspected of being involved in initiating the disease are nitrosamines found in
      urine. In this study a nitrosamine found in the urine of smokers was tested using
      a tissue culture model of normal human urothelium. Explant cultures were
      established from ureters and exposed to 5 ng/ml of the derivative. This level had
      been demonstrated previously to induce a variety of changes associated with
      initiation of carcinogenesis. Proliferation of the cultures was increased
      following exposure to the carcinogen, and the gap junction intercellular
      communication was reversibly inhibited. Examination of the connexin 43 protein
      and message status showed that the mRNA was unaffected, but the protein was not
      detectable using anti-connexin 43 antibody. The expression of the protein
      recovered within 24 h of removal of the carcinogen, indicating that the continued
      presence of the agent was necessary. Given the roles of cell proliferation and
      cell communication in carcinogenesis, the results may suggest a mechanism
      involving pre- or post-initiation deregulation of cell communication systems.
      Whether the enhanced growth is a separate effect or a consequence of reduced
      communication is an intriguing question.

PMID- 8979273
TI  - Scheimpflug attachment for ophthalmological slitlamps.
AB  - Scheimpflug imaging is a technique suited for the quantification of minor
      opacities of the human eye lens. In the past, several Scheimpflug systems have
      been developed but being fairly complex and expensive, they have not been widely
      used. At present, only one instrument is on the market. For these reasons, a new
      Scheimpflug attachment-to be operated in connection with a slitlamp-was
      developed. The system is of compact, light-weight and modular design and consists
      of commercially available components. The Scheimpflug image, recorded by a CCD
      camera, is digitized in real time by a PC. It is displayed on a video monitor for
      on-line alignment. The data obtained are permanently stored on optical disk and
      are available for further analysis. The design of a prototype instrument is
      described. The practical applicability of the instrument and the high quality of
      the images is demonstrated.

PMID- 8979274
TI  - Immunohistochemical study of 28-kD heat shock protein in the lens of young human
      embryos.
AB  - The localization of 28-kD heat shock protein (HSP28) in the lenses of human
      embryos (Carnegie stages 13-21) was studied immunohistochemically using
      antibodies for HSP28. At stage 13, HSP28 was observed in the lens placode. At
      stage 15, when the lens vesicle is formed by the invagination of the lens
      placode, HSP28 was observed in the posterior portion of the lens vesicle. From
      stages 16 to 18, when the posterior portion of the lens epithelium elongates
      toward the anterior lens epithelium and forms the primary lens fiber, HSP28 was
      observed in the apical and basal sides of the primary lens fiber. At stage 19,
      when the primary lens fiber attaches to the anterior lens epithelium,
      immunoreactivity to HSP28 appeared in the anterior lens epithelium. At stage 21,
      the anterior lens epithelium and the equator portion of the lens, where the
      secondary lens fiber is formed, were intensely immunoreactive to HSP28. Although
      alpha B-crystallin is thought to be one of the small HSPs, the distribution of
      HSP28 in the lenses of human embryos was different from that of alpha B
      crystallin which we previously reported.

PMID- 8979275
TI  - A technical approach to the evaluation of glucose oxidation: implications for
      diabetic cataract.
AB  - Oxidative stress has recently been involved in a number of diseases including
      development of diabetic cataract. If hyperglycemia is the relevant factor in
      diabetes, then it is reasonable to assume that under physiological conditions
      glucose may be toxic. The mechanisms involved in such a type of glucose
      'toxicity' are still poorly understood but may involve glucose autoxidation. In
      this study we discuss a new methodological approach to the evaluation of glucose
      induced oxidative damage to bovine lens membranes. The method is based on the
      incorporation of a fluorescent probe (parinaric acid) into lens membranes. The
      oxidative degradation of the probe is evaluated by monitoring its fluorescence
      decrease. It was possible to show that glucose may induce oxidative damage in the
      presence of trace amounts of transition metals. Furthermore, the data obtained by
      monitoring oxidative degradation of parinaric acid could be related to the amount
      of thiobarbituric acid-reactive substances formed under identical periods of
      time. The technique was shown to be reproducible, straightforward and highly
      sensitive as compared to other classical methods. Moreover, this methodological
      approach allows not only the evaluation of the extension of oxidative stress
      inflicted upon lens membranes but also the evaluation of the antioxidant effect
      of various compounds including some drugs with a potential anticataractogenic
      effect.

PMID- 8979276
TI  - Common antigenicity between Yersinia enterocolitica-derived heat-shock protein
      and the retina, and its role in uveitis.
AB  - Yersinia enterocolitica-derived heat-shock protein (HSP60) was recently
      demonstrated to be associated with certain systemic autoimmune diseases. A role
      for HSP60 is also suspected in the pathogenesis of some types of uveitis believed
      to involve autoimmune mechanisms, such as Behcet's disease. We report our results
      on the role of HSP60 in patients with uveitis. HSP60 was subjected to
      electrophoresis in immunoblot analysis, and then allowed to react with sera from
      patients with uveitis in order to detect the presence of anti-HSP60 antibody.
      Tissue extracts from human and bovine retina were also electrophoresed, and then
      treated with anti-HSP60 monoclonal antibodies to determine whether or not the
      antibodies recognized ocular tissues. Immunoblot analysis revealed anti-HSP60
      antibodies in patient sera. Furthermore, anti-HSP60 monoclonal antibodies reacted
      against the 60-kD protein derived from human and bovine retinal extracts. These
      immunological cross-reactions between HSP60 and the retina demonstrate a common
      antigenicity. Furthermore, detection of specific antibody against HSP60 in
      patient sera suggests that this common antigenicity between HSP60 and the retina
      may be related to the pathogenesis of uveoretinitis in some cases.

PMID- 8979277
TI  - Relationship of the strain and the intraocular amount of herpes simplex virus
      types 1 and 2 in the induction of anterior-chamber-associated immune deviation.
AB  - We investigated the induction of anterior-chamber-associated immune deviation
      (ACAID) by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Two strains of
      HSV-1 (VR-3 and F) and four strains of HSV-2 (UW-268, 186, SL, and MS) were
      inactivated with ultraviolet light, and the anterior chamber of BALB/c mice was
      inoculated with a viral strain. Immunization against delayed-type
      hypersensitivity (DTH) was done subcutaneously on day 7 after anterior chamber
      inoculation. On day 10 after DTH immunization, each virus was inoculated into the
      foot pad. DTH was evaluated by measuring the foot pad thickness at 24 h after the
      inoculation into the foot pad. DTH was suppressed by anterior chamber inoculation
      with more than 10(3) plaque-forming units (PFU) of the VR-3, UW-268, 186, and SL
      strains, and with 10(5) PFU of the F strain, but not by the MS strain. Until now,
      HSV-2 was believed not to induce ACAID, however, our results indicate that some
      HSV-2 strains induce ACAID.ACAID induction by HSV-1 and HSV-2 may depend on both
      the viral strain and the amount of ocular viral antigen.

PMID- 8979278
TI  - Dual immunodetection and hybridisation in situ of opsin mRNA and rhodopsin
      protein in retinal sections.
AB  - We describe a simple method for combining in situ hybridisation and
      immunohistochemistry on the same retinal section. The technique was developed
      using a radiolabelled cDNA probe for opsin and an antibody (ROS1F4) against
      rhodopsin. This method retains the antigenic sites if immunocytochemistry is
      performed prior to in situ hybridisation. Opsin mRNA was found in the
      photoreceptor inner segment with rhodopsin immunolocalised to the photoreceptor
      outer segments. The technique should be applicable to numerous situations
      including analysis of the sequence of events in the expression and synthesis of
      the various opsins during retinal development and degeneration.

PMID- 8979279
TI  - ERG campimetry using a multi-input stimulation technique for mapping of retinal
      function in the central visual field.
AB  - The m-sequence stimulation technique that has previously been described allows
      simultaneous recording of many local electroretinograms (ERGs). For topographical
      mapping of cone function in the central retina ERG traces from 61 retinal areas
      were recorded during a 4-min period in 20 normal volunteers and 4 patients with
      age-related macular degeneration, Stargardt's disease, choroidal atrophy, and
      polymyalgia associated with visual field loss. The local photopic luminance
      response was analyzed in each of the 61 areas. In the 2 patients with macular
      disease central defects were detected, in the remaining patients local defects
      were found outside the macular region. The method of multifocal ERG recordings
      provides the possibility of objective testing of visual fields when the outer
      retinal layers are affected.

PMID- 8979280
TI  - Effect of dapiprazole, an alpha-adrenergic blocking agent, on aqueous humor
      dynamics in pigmentary glaucoma.
AB  - PURPOSE: In this investigation the authors studied the effect of dapiprazole, an
      alpha-adrenergic blocking agent, on aqueous humor dynamics in patients affected
      with pigmentary glaucoma. METHODS: Dapiprazole 0.5% eye drops were administered 3
      times daily as adjunctive therapy to 16 pigmentary glaucoma patients in addition
      to timolol 0.5% eye drops twice daily. Computerized tonography was performed
      before and 3, 12 and 36 months after dapiprazole treatment. Sixteen sex- and age
      matched pigmentary glaucoma patients treated with timolol 0.5% eye drops alone
      were used as a control group. RESULTS: After 36 months of follow-up, the
      dapiprazole-treated group showed a significant increase in total outflow facility
      (C, from 0.17 +/- 0.04 to 0.22 +/- 0.07 ml min-1 mm Hg-1; p = 0.010, paired t
      test) and Po/C ratio (Q) significantly decreased from 113.39 +/- 31.02 to 89.22
      +/- 51.66 (p = 0.036, paired t test). CONCLUSIONS: Our results show that the
      introduction of dapiprazole in the therapy of pigmentary glaucoma may be useful
      in the long-term management of these patients. Its mechanism of action is likely
      to be due to iridoplegia; in fact, a decrease in the shedding of pigment occurs,
      with time, the outflow facility increases and the pigment clearance from the
      trabecular meshwork is enhanced.

PMID- 8979281
TI  - Metabolic analysis of the rabbit cornea by proton nuclear magnetic resonance
      spectroscopy.
AB  - Perchloric acid extracts of the rabbit cornea were analyzed by high-resolution 1H
      NMR spectroscopy, including the two-dimensional shift-correlated (COSY)
      technique. Numerous metabolites including leucine/isoleucine, 3-hydroxybutyrate,
      valine, lactate, alanine, lysine, acetate, glutamate, creatine/phosphocreatine,
      taurine, glycine, inositol, glucose, tyrosine, phenylalanine, histidine,
      adenosine and formate have been simultaneously detected and identified in the NMR
      spectra. Concentrations of some of these were also determined. Of particular
      importance are the detection and identification of hypotaurine in the corneal
      tissue. Hypotaurine is a precursor of the synthesis of taurine and may act as an
      antioxidant. Moreover, the presence of choline, a precursor for acetylcholine,
      was established. This novel metabolite profile of the cornea obtained by high
      resolution 1H NMR spectroscopy may be of value in the study of pathologic and
      toxic disorders.

PMID- 8979282
TI  - Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed
      formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric
      Lipid Study.
AB  - The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty
      acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA,
      20:4n-6), which are present in human milk but not in most infant formulas. In the
      present study of 134 formula-fed and 63 breast-fed infants, we prospectively
      evaluated whether providing a source of DHA and AA or DHA alone in formula would
      increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance
      visual function, or affect growth during the first year. Healthy term infants < 7
      d old were randomized to be fed formulas containing linoleic acid (approximately
      10% kcal) and alpha-linolenic acid (approximately 1% kcal) plus (1) no added LCP
      fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%)
      from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil
      (DHA formula). A breast-fed group was studied concurrently and permitted formula
      supplementation after 3 mo. Visual acuity was measured using both the acuity card
      procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants
      fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in
      the breast-fed group. Infants fed the AA + DHA formula had levels of both LCP
      within approximately 10% of the values for infants in the breast-fed group, and
      infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA
      levels. There were no differences in growth or in visual function during this 12
      mo feeding study.

PMID- 8979283
TI  - Effect of maternal diabetes upon fetal rat myocardial and skeletal muscle glucose
      transporters.
AB  - We investigated the effect of streptozotocin-induced short-term maternal diabetes
      upon fetal rat myocardial and skeletal muscle glucose transporter Glut 1 (basal
      form) and Glut 4 (insulin-responsive form) protein concentrations by Western blot
      analysis. In the severely diabetic group (SEVERE-D, n = 17), a 3-fold increase in
      maternal and fetal glucose concentrations (p < 0.01) was associated with a 3-fold
      decline in maternal (p < 0.01) with no change in fetal insulin levels when
      compared with the streptozotocin-treated nondiabetic (n = 10) and vehicle-treated
      control (control, n = 14) groups. These changes in the SEVERE-D group when
      compared with controls were associated with a 30 and 65% decline, respectively,
      in fetal myocardial and skeletal muscle (forelimb and hind limb) Glut 1 protein
      concentrations. The fetal myocardium also demonstrated a 45% decline in Glut 4
      protein levels. Fetal skeletal muscle Glut 4 protein, which was expressed only at
      very low levels in controls showed no change in SEVERE-D. Immunohistochemical
      analysis revealed a myocyte-plasma membrane association of Glut 1 and an
      intracellular Glut 4 distribution in the fetal myocardium and skeletal muscle. No
      Glut 1 immunoreactivity was noted in either the fetal myocardial or skeletal
      muscle perineural sheaths, blood vessels, or the entrapped fetal red blood cells.
      This subcellular localization pattern was unaltered in all three treatment
      groups. We conclude that maternal diabetes causing fetal hyperglycemia with
      normoinsulinemia suppresses fetal myocardial Glut 1 and Glut 4 and fetal skeletal
      muscle Glut 1. The decline in the plasma membrane associated Glut 1
      concentrations may serve a protective function by reducing the glucose transport
      rate into fetal myocardial and skeletal muscle cells, which otherwise could be
      vulnerable to high circulating glucose. The in-utero maternal diabetes induced
      decrease in fetal myocardial intracellular-Glut 4 concentration could herald the
      emergence of insulin resistance.

PMID- 8979284
TI  - Effect of glucocorticoids on neonatal rabbit renal cortical sodium-inorganic
      phosphate messenger RNA and protein abundance.
AB  - Administration of glucocorticoids to neonates increases proximal tubule volume
      absorption by increasing glucose, bicarbonate, and amino acid transport. We have
      recently demonstrated that glucocorticoids may contribute to the maturational
      decrease in phosphate transport. This study examines the maturation of NaPi-6
      [the regulated proximal tubule sodium-inorganic phosphate (Na-Pi) transporter]
      mRNA and protein abundance and the mechanism for the decrease in phosphate
      transport by glucocorticoids. Weaned young rabbits (5 wk) had a 2-fold greater
      brush border membrane NaPi-6 protein abundance than that measured in adults.
      Renal cortical NaPi-6 mRNA abundance was comparable in neonates (less than 10 d
      of age) and adults. Renal brush border membrane vesicles from dexamethasone
      treated neonatal rabbits (10 micrograms/100 g of body weight for 4 d) had a lower
      rate of Na-Pi transport than vehicle-treated controls (46.8 +/- 6.5 versus 71.0
      +/- 9.0 pmol 32P/10 s/mg of protein, p < 0.05). Abundance of NaPi-6 protein in
      brush border membrane vesicles was 3-fold lower in newborn rabbits treated with
      pharmacologic doses of dexamethasone than in vehicle-treated controls. NaPi-6
      mRNA abundance was the same in both groups. NaPi-1, a brush border membrane
      phosphate transporter which is also an anion channel, mRNA, and protein abundance
      was not affected by glucocorticoids. These data demonstrate that there is a
      maturational decrease in NaPi-6 protein abundance and that glucocorticoids
      decrease neonatal phosphate transport, at least in part, by reducing the number
      of Na-Pi transporters.

PMID- 8979285
TI  - 11 beta-Hydroxysteroid dehydrogenase and its role in the syndrome of apparent
      mineralocorticoid excess.
AB  - Aldosterone, the most important mineralocorticoid, regulates electrolyte
      excretion and intravascular volume mainly through its effects on renal distal
      tubules and cortical collecting ducts, where it acts to increase sodium
      resorption from and potassium excretion into the urine. Excess secretion of
      aldosterone or other mineralocorticoids, or abnormal sensitivity to
      mineralocorticoids, may results in hypokalemia, suppressed plasma renin activity,
      and hypertension. The syndrome of apparent mineralocorticoid excess (AME) is an
      inherited form of hypertension in which 11 beta-hydroxysteroid dehydrogenase (11
      beta-HSD) is defective. This enzyme converts cortisol to its inactive metabolite,
      cortisone. Because mineralocorticoid receptors themselves have similar affinities
      for cortisol and aldosterone, it is hypothesized that the deficiency allows these
      receptors to be occupied by cortisol, which normally circulates at levels far
      higher than those of aldosterone. We cloned cDNA and genes encoding two isozymes
      of 11 beta-HSD. The liver (L) or type 1 isozyme has relatively low affinity for
      steroids, is expressed at high levels in the liver but poorly in the kidney, and
      is not defective in AME. The kidney (K) or type 2 isozyme has high steroid
      affinity and is expressed at high levels in the kidney and placenta. Mutations in
      the gene for the latter isozyme have been detected in all kindreds with AME.
      Moreover, the in vitro enzymatic activity conferred by each mutation is strongly
      correlated with the ratio of cortisol to cortisone metabolites in the urine
      [tetrahydrocortisone (THF) +allo-THF]/THE. This suggests that the biochemical
      phenotype of AME is largely determined by genotype.

PMID- 8979286
TI  - Growth of patients with 21-hydroxylase deficiency: an analysis of the factors
      influencing adult height.
AB  - Growth of 92 Finnish patients with 21-hydroxylase deficiency (21-OHD) was
      analyzed retrospectively to study growth both before the diagnosis and during
      glucocorticoid substitution therapy. The patients were divided into two groups:
      those diagnosed at infancy (56 patients) and those diagnosed after the age of 1 y
      (36 patients). Birth lengths of those boys and girls diagnosed at infancy were
      greater than the national mean birth lengths (p < 0.001). Mean relative length
      diminished from +0.8 SD score (SDS) at birth to -1.0 SDS by the age of 1 y. Adult
      height was -1.0 SDS (159.9 cm) for women and -0.8 SDS (173.6 cm) for men. The
      difference from national mean height was significant only for women (p = 0.026).
      Mean relative weight during childhood correlated negatively with adult stature (r
      = -0.620; p = 0.006). In the group of children diagnosed later in their
      childhood, growth was already accelerated at infancy from +0.2 SDS at birth to
      +0.7 SDS by the age of 1 y (p = 0.023). The final height of girls diagnosed later
      in childhood was within normal limits (-0.5 SDS; 162.1 cm), whereas it was low in
      the corresponding group of boys (-2.1 SDS; 165.3 cm). Our data show increased
      mean birth length in babies with early diagnosis of 21-OHD and growth
      acceleration at infancy in children diagnosed later in their childhood,
      reflecting the growth accelerating effect of adrenal hyperandrogenism early
      during fetal life and infancy. To improve final height in patients with 21-OHD,
      lower doses of hydrocortisone should be used at infancy, and special attention
      should be paid to boys diagnosed later in childhood.

PMID- 8979287
TI  - Early developmental profiles of plasma corticosterone are altered by birth
      condition in the rat: a comparison of vaginal birth, cesarean section, and
      cesarean section with added anoxia.
AB  - Circulating glucocorticoids play a role during the immediate postnatal period in
      adapting the neonate to extrauterine life and are also thought to influence
      tissue development and function in the later postnatal period. In the present
      study we have used a rat model to test whether birth by cesarean section (C
      section), either alone or with an added period of acute anoxia, affects the
      development profile of basal corticosterone secretion during the first 5 wk of
      life. Plasma levels of total corticosterone and of corticosteroid-binding
      globulin were measured at various times after birth in rats born vaginally, by C
      section, or by C-section with 15 min of added anoxia. These measures allowed for
      calculation of levels of free, biologically active, corticosterone. Under all
      conditions, total corticosterone appeared to accurately reflect levels of free
      corticosterone. Plasma corticosterone levels measured immediately (< 5 min) after
      birth were similar in male rat pups born vaginally, by C-section, or by C-section
      with added anoxia, whereas female pups born by C-section showed a significant
      increase in free corticosterone at birth, in comparison with vaginally born
      females. Both male and female animals born by C-section showed a reduction in
      plasma corticosterone at 1 h (male: 31% of control, p < 0.01; female: 45% of
      control, p < 0.05) and at 7 d (male: 61% of control, p < 0.01; female: 55% of
      control, p < 0.05) after birth, in comparison with vaginally born controls. In
      animals born by C-section with added anoxia, significant reductions in plasma
      corticosterone were observed for males at 1 h (58% of control; p < 0.05) and for
      females at 7 d (62% of control; p < 0.05) after birth. At 14 d of age,
      corticosterone levels were higher in male rats born by C-section either with
      (227% of control; p < 0.05) or without (239% of control; p < 0.05) added anoxia,
      in comparison with vaginally born controls. Thus C-section birth produces an
      early rise in plasma corticosterone on d 14 away from the low values associated
      with the adrenal quiescent period in the first 1-2 wk in the rat. By 35 d of age,
      there were no differences in plasma corticosterone attributable to C-section
      birth and/or acute birth anoxia, in either male or female rats. It is concluded
      that, in a rat model, birth by C-section has significant effects on the profile
      of plasma corticosterone during the early weeks of development, a period though
      to be critical for effects of corticosteroids on developing tissues. Because the
      rat at birth is developmentally less mature than is the term human neonate, these
      findings may have implications for development of the premature human neonate.

PMID- 8979288
TI  - Knemometry, urine cortisol excretion, and measures of the insulin-like growth
      factor axis and collagen turnover in children treated with inhaled
      glucocorticosteroids.
AB  - Correlations between knemometric (lower leg length) growth rates and urine free
      cortisol excretion, respectively, and serum concentrations of IGF-I, IGF binding
      protein-3, osteocalcin, carboxy terminal propeptide of type I collagen (PICP),
      carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen
      (ICTP), and amino terminal propeptide of type III procollagen (PIIINP) were
      investigated in 17 asthmatic children aged 7-14 y during treatment with
      fluticasone propionate, 200 micrograms, and beclomethasone dipropionate, 400 and
      800 micrograms/d, taken from dry powder inhalers. The study was a double blind,
      crossover trial with three active treatment periods and two wash-out periods. All
      periods were 15 d long. Overnight urine free cortisol/ creatinine x 10(6) did not
      correlate with knemometric growth rates or any of the serum markers. Significant
      correlations (Pearson's correlation coefficient, P) between knemometric growth
      rates and IGF-I (0.41; 0.006), IGFBP-3 (0.35; 0.02), PICP (0.44; 0.003), ICTP
      (0.35; 0.001), and PIIINP (0.46; 0.002) were found. Compared with fluticasone
      propionate, 200 micrograms, beclomethasone dipropionate, 400 and 800 micrograms,
      caused significant suppression of lower leg growth rate (F = 12.41; p = 0.002,
      and F = 23.30; p = 0.0001, respectively) and of urine free cortisol/creatinine x
      10(6) (F = 10.52; p = 0.003, and F = 13.74; p = 0.001). Beclomethasone, 800
      micrograms, caused suppression of PICP compared with fluticasone propionate, 200
      micrograms (F = 8.31; p = 0.008), and beclomethasone, 400 micrograms (F = 7.53; p
      = 0.01). Both low (F = 6.82; p = 0.02) and high (F = 23.35; p = 0.0001) doses of
      beclomethasone were associated with reduced concentrations of ICTP, the high dose
      being the most suppressive (F = 4.42; p = 0.05). Beclomethasone 400 (F = 9.75; p
      = 0.004) and 800 micrograms (F = 23.61; p = 0.0001) resulted in reduced levels of
      PIIINP. Reduced short-term knemometric growth rates in children treated with
      inhaled glucocorticosteroids reflect suppressive effects on type I and type III
      collagen turnover.

PMID- 8979289
TI  - Developmental and afterload stress regulation of heat shock proteins in the ovine
      myocardium.
AB  - Heat shock proteins (hsps) are produced in the myocardium in response to stresses
      such as ischemia, hyperthermia, and increased afterload. The role of these stress
      proteins in the developing myocardium is unknown. Expression of the inducible
      (hsp 72) and cognate (hsc 73) hsps was determined in the immature ovine
      myocardium during the perinatal transition, and their role in subsequent
      myocardial growth was examined. hsp synthesis was also studied during acute
      afterload stress in newborns by aortic banding to a gradient of 50 torr for 4 h.
      Expression of the inducible (hsp 72) isoform is developmentally regulated in both
      right and left ventricles: low levels in the fetus, increasing throughout
      development, and peaking in the 14-25-d newborn and adult. The cognate (hsc 73)
      isoform remains unchanged during development in the left ventricle but decreases
      with age in the right ventricle. The inducible (hsp 72) isoform is also
      developmentally regulated in the lung, increasing postnatally to a peak in the 14
      25-d-old and adult sheep. Finally, newborn myocardium demonstrated a rapid
      increase in hsp expression in response to afterload stress, similar to that seen
      in the adult.

PMID- 8979290
TI  - Perinatal left ventricular performance in fetal sheep: interaction between oxygen
      ventilation and contractility.
AB  - Left ventricular (LV) output nearly triples at birth, in association with
      increases in serum catecholamines. Similar increases in catecholamines in utero,
      however, do not increase output. We hypothesized that catecholamines increase
      contractility in utero, but that output cannot increase until LV loading
      conditions are changed by oxygen ventilation. To address this hypothesis, we
      studied nine fetal sheep acutely placed in a warm water bath (40 degrees C).
      Conductance and manometric catheters were placed in the LV to generate pressure
      volume loops during caval occlusion in the nonventilated and oxygen-ventilated
      states, each under control, dobutamine, and propranolol conditions. Contractility
      was estimated by the end-systolic pressure-volume relationship, preload by end
      diastolic volume, and afterload by arterial elastance. Oxygen ventilation
      increased LV output 1.4-fold, despite a decrease in contractility to about three
      fourths of the nonventilated value. Heart rate remained constant, whereas preload
      increased and afterload decreased significantly. During oxygen ventilation,
      dobutamine increased output to 2.3 times the control, nonventilated value,
      associated with increases in contractility and heart rate and no change in
      preload and afterload. Although dobutamine increased contractility and heart rate
      similarly in the nonventilated and oxygen ventilated states, output increased
      significantly more during ventilation. Similarly, propranolol decreased
      contractility and heart rate equally in both states, but output decreased far
      more during ventilation. Thus, oxygen ventilation is associated with advantageous
      changes in LV load such that the positive inotropic and chronotropic effects of
      dobutamine are translated into greater increases in LV output.

PMID- 8979291
TI  - Developmental changes in the contractile system of the mesenteric small artery of
      rabbit.
AB  - This study investigated developmental changes in the contractile system of the
      mesenteric small arteries of the rabbit. Arteries about 1 mm in length and 100
      250 microns in internal diameter were dissected out from the mesenteric bed of
      the fetus (29 d of gestation), newborn (3-5 d old), and adult rabbit. Vascular
      contraction was induced by high KCl concentration, and contractile force was
      measured using a tension transducer. The sensitivity of vascular contraction to
      high KCl was similar in the three age groups. To determine the role of Ca influx
      across the sarcolemma in vascular contraction, the vasorelaxant effect of
      diltiazem was studied in the artery precontracted with high KCl concentration.
      The vasorelaxant effect of diltiazem in the fetus and newborn was less than in
      the adult. To estimate the size of the intracellular Ca pool, caffeine-induced
      and noradrenaline-induced contraction were measured in the Ca- and Na-free
      solution. In the fetus and newborn, both the caffeine-induced contraction and
      noradrenaline-induced contraction were greater than in the adult. The
      ultrastructural study showed that the endoplasmic reticulum was abundant in the
      fetus and newborn, and it was scarce in the adult. These data indicate that the
      dependency of vascular contraction on Ca influx across the sarcolemma increases
      and the intracellular Ca store decreases with development in the mesenteric
      resistance arteries.

PMID- 8979292
TI  - Age-related effects of cardiac sympathetic denervation on the responses to
      cardiopulmonary receptor stimulation in piglets.
AB  - The effects of right stellate ganglionectomy (RSG) and bilateral stellate
      ganglionectomy (BSG) on cardiovascular responses to phenyl biguanide (PBG, 80
      micrograms/kg) were studied in 1- and 8-wk-old piglets. Animals were anesthetized
      with Saffan, paralyzed, thoractomized, and ventilated with 100% O2. Recordings of
      the ECG (lead II) and aortic pressure (AoP) were used to compute the maximum R-R
      interval, heart rate (HR), and mean AoP, and to determine the occurrence of
      atrioventricular conduction block (AVB). Right atrial injections of PBG in 1-wk
      old piglets elicited AVB as well as decreases in AoP and HR in all animals; this
      response pattern was not altered by either RSG or BSG. The PBG response of
      neurally intact 8-wk-old animals was comprised of a decrease of HR without change
      in AoP; AVB occurred in three of six animals. After RSG or BSG, AoP decreased
      along with decreased HR, and now AVB occurred in all animals; changes of AoP and
      maximum R-R interval were greater after BSG than after RSG. These results suggest
      that the stellate ganglia exert a neuroprotective influence on cardiovascular
      function, requiring some degree of maturation for expression. Our findings
      support the hypothesis that an imbalance of cardiac autonomic innervation
      favoring parasympathetic activity may produce immature responses to
      cardiopulmonary afferent stimulation in older maturing animals.

PMID- 8979293
TI  - The effects of treatment with indomethacin on the cerebral vasculature of newborn
      piglets before and during hemorrhagic hypotension.
AB  - Substantial physiologic data point to a significant role for dilator prostanoids
      in the regulation of cerebral vascular tone in newborn pigs. This study begins to
      address the hypothesis that multiple dilator systems, including prostanoids, can
      provide for the initiation and maintenance of cerebral vasodilation in response
      to hypotension. Piglets were anesthetized, and cranial windows were implanted.
      Hypotension was achieved by hemorrhage to 50% of the control arterial pressure
      and maintained for 10 min. Each piglet served as its own control by the induction
      of hypotension and return to normotension before treatment. Pial arterioles
      dilated (38 +/- 5% increase in diameter) in response to hypotension. Pretreatment
      with indomethacin (5 mg/kg i.v.) at 20 min and immediately before hypotension did
      not block this response (28 +/- 7% and 23 +/- 9% increase in diameter,
      respectively). In contrast, when indomethacin was administered 10 min into the
      hypotensive period, the dilated arterioles (106 +/- 6 microns) constricted to the
      normotensive diameter (75 +/- 5 microns) and remained constricted for the
      duration of the observation. These findings suggest that compensatory mechanisms
      provide for cerebral vasodilation when prostanoid synthesis and prostacyclin
      receptors are blocked before hemorrhagic hypotension. However, removal of
      prostanoids after vasodilation is established in response to hypotension causes
      constriction without compensation from alternative mechanisms. Awareness of these
      findings may be important when considering giving indomethacin to sick preterm
      infants during periods of cardiac instability.

PMID- 8979294
TI  - Protein kinase Cs and tyrosine kinases in permissive action of prostacyclin on
      cerebrovascular regulation in newborn pigs.
AB  - The involvement of protein kinase C (PKC) and protein tyrosine kinase (PTK) in
      hypercapnia-induced cerebral vasodilation in newborn pigs was investigated with
      closed cranial windows using the PKC stimulator phorbol 12-myristate 13-acetate
      (PMA), and the PTK inhibitors, genistein and herbimycin A. The influence of
      prostaglandin I2 was eliminated using the prostaglandin cyclooxygenase inhibitor,
      indomethacin. Changes in pial arteriolar diameters in response to hypercapnia
      [partial pressure of arterial CO2 approximately 9.3 kPa (70 torr)] were analyzed.
      Genistein (40 micrograms/mL), herbimycin A (10 microM), or PMA (1 microM) did not
      affect cerebral vasodilation to hypercapnia when applied topically. Indomethacin
      (5 mg/kg i.v.) treatment blocked the dilation to hypercapnia and attenuated
      hypercapnia-induced increase in cortical cAMP. Genistein and herbimycin A
      restored the response to hypercapnia to indomethacin-treated piglets. PMA also
      restored the pial arteriolar dilation and the cAMP response to hypercapnia to
      indomethacin-treated piglets. One-hour exposure to 10 microM PMA, to down
      regulate PKC, blocked vasodilation to hypercapnia but did not inhibit
      vasodilation to sodium nitroprusside. After prolonged (2 h) topical exposure of
      indomethacin-treated piglets to 10 microM PMA, neither genistein nor iloprost
      could restore dilation to hypercapnia. These results indicate that PKC
      stimulation and/or PTK inhibition may permit hypercapnia-induced vasodilation.
      These data further suggest that PKC is downstream from PTK in the regulatory
      pathway. Because previous data showed prostaglandin I2 at subdilator
      concentrations can also return dilation to hypercapnia to piglets treated with
      indomethacin, prostaglandin I2 could provide its permissive input by activating
      PKC and/or inhibiting PTK.

PMID- 8979295
TI  - The effect of hypercapnia and hypercapnia associated with central cooling on
      breathing in unanesthetized fetal lambs.
AB  - In utero breathing activity is present periodically, but it must become
      continuous at birth. We investigated the effect of hypercapnia and of hypercapnia
      combined with central cooling on fetal breathing in seven chronically
      instrumented fetal lambs of 131-134-d gestation, using an extracorporeal membrane
      oxygenation (ECMO) system to control fetal blood gases and fetal temperature.
      During fetal hypercapnia (from a partial pressure of arterial CO2 (Paco2) 6.18 +/
      0.11 kPa to Paco2 7.39 +/- 0.15 kPa) frequency, amplitude, and incidence of
      fetal breathing movements during low voltage electrocortical activity (LV ECoG)
      increased significantly compared with isocapnic control on ECMO, but breathing
      remained absent during high voltage electrocortical activity (HV ECoG). During
      hypercapnia accompanied by central cooling (Paco2 7.90 +/- 0.13 kPa, temperature
      decreased by 2.1 degrees C) there were similar changes in fetal breathing
      movements during LV ECoG, but in four out of seven fetuses fetal breathing
      movements continued throughout HV ECoG. Hypercapnia accompanied by central
      cooling can thus override the inhibitory effects of HV ECoG on fetal breathing
      movements. This may be due to changes in sensitivity to CO2 produced by an
      increase in afferent input to the CNS.

PMID- 8979297
TI  - Granulocyte-macrophage colony-stimulating factor in amniotic fluid and in airway
      specimens of newborn infants.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that
      promotes white cell maturation, participates in the metabolism of pulmonary
      surfactant. Little is known on the production of GM-CSF during pregnancy or the
      neonatal period. We studied how the concentrations of GM-CSF in amniotic fluid
      (AF) or in tracheal aspirates (TA) of newborn infants are influenced by length of
      gestation, postnatal age, as well as conditions affecting the mother or the
      fetus. One hundred and forty-three AF samples from 143 pregnant patients
      (gestational age range, 28-42 wk) and 202 TA samples from 82 neonates
      (gestational age, 24-42.5 wk, postnatal age 0.2 d to 4 wk) were analyzed for GM
      CSF using ELISA. In patients with intact membranes, AF GM-CSF increased as a
      function of gestational age; the concentrations were below 7.5 ng/L (detection
      limit of the assay) (n = 5), 18.6 +/- 2.3 ng/L (n = 56), and 56.7 +/- 7.9 ng/L (n
      = 58) at gestational ages between 28 and 32 wk, between 32 and 37 wk, and in term
      patients, respectively (linear regression: r = 0.404, p = 0.001). Among patients
      at less than 33 wk of gestation, those with intact membranes had a median AF GM
      CSF concentration under the detection limit (n = 7), whereas in those with
      preterm premature rupture of membranes, the concentration was 50.1 +/- 22.2 ng/L
      (n = 16) (p = 0.002). Among term patients, those in labor had higher AF GM-CSF
      than those without signs of labor. TA GM-CSF at less than 12 h of age correlated
      with gestational age (r = 0.654, p = 0.0002, n = 28); thereafter, TA GM-CSF
      increased, and gestation dependence disappeared. We conclude that GM-CSF in AF
      and in fetal lung liquid is developmentally regulated and GM-CSF production
      increases in inflammatory conditions during pregnancy.

PMID- 8979296
TI  - Brief repeated umbilical cord occlusions cause sustained cytotoxic cerebral edema
      and focal infarcts in near-term fetal lambs.
AB  - The aim of this study was to determine whether asphyxia induced by clinically
      relevant, brief repetitive umbilical cord occlusions is associated with cerebral
      compromise. Chronically instrumented fetal lambs were studied at 126.5 +/- 2.8 d
      of gestation (mean +/- SD, term 147 d). Occlusions were performed 1 out of every
      2.5 min (group I, n = 7), 2 out of every 5 min (group II, n = 9), or not at all
      (shams, group III, n = 5), and discontinued at a predetermined threshold of
      severe or persistent hypotension. After 58 +/- 8 and 24 +/- 2 occlusions, in
      groups I and II, respectively, the pH was 6.83 +/- 0.09, Pco2 9.52 +/- 1.4 kPa,
      base excess -23.5 +/- 3.7 mM, and lactate 14.1 +/- 1.6 mM. Two fetuses (out of
      group II) did not recover from the final occlusion. Ongoing asphyxia was
      associated with progressive suppression of the EEG, which occurred faster and
      with more epileptiform and spike activity in group II. Cortical impedance
      remained elevated for 15.0 +/- 4.0 and 11.5 +/- 4.4 h, for groups I and II,
      respectively (NS). Focal infarcts occurred in the parasagittal cortex, thalamus,
      and cerebellum, in 6 out of 14 surviving asphyxiated fetuses. Mild selective
      neuronal loss was observed in these regions in 13 out of 14 fetuses. Infarction
      was associated with a longer period of blood pressure below baseline levels, with
      more epileptiform activity, and with slower normalization of the EEG. In a
      paradigm mimicking birth asphyxia, histologic damage similar to that observed
      clinically was found. The results suggest that brief repeated insults interact,
      leading to cardiac compromise and cumulative cell membrane damage in the fetal
      cerebrum.

PMID- 8979298
TI  - Interleukin-10 production by cord blood mononuclear cells.
AB  - The production of IL-10 by newborns has not been studied in much detail. We
      analyzed the IL-10 production by, and surface marker distribution of, cord blood
      mononuclear cells (n = 47); adult peripheral blood mononuclear cells (n = 30)
      were used as controls. Both the baseline (0.79 versus 1.54 ng/mL, p = 0.001) and
      lipopolysaccharide-stimulated (1.20 versus 2.88 ng/mL, p = 0.003) levels of IL-10
      production were significantly lower in newborns than in adults. No significant
      differences were observed after stimulation with concanavalin A. Both cord blood
      and adult CD19+CD5+ cells were able to produce IL-10; however, the level of
      production was only an average of 16% of the total stimulated IL-10 production by
      unfractionated cells, indicating that CD5+ B cells are not the primary source of
      IL-10 in either adults or newborns. In newborns, the proportion of naive
      CD4+CD45RA+ cells was inversely correlated with IL-10 response to
      lipopolysaccharide (r = -0.49, p = 0.004) indicating a role for maturing T cells
      in neonatal IL-10 production; the number of macrophages was not significantly
      correlated with IL-10 response (r = 0.30, p = 0.10). In contrast, in adults IL-10
      production correlated with the number of macrophages (r = 0.49, p = 0.01) but not
      CD4+CD45RA+ cells (r = -0.06, p = 0.77). We conclude that newborns produce less
      IL-10 than adults; the primary cells of origin and the regulatory mechanisms may
      be different from those observed in adults.

PMID- 8979299
TI  - Modified natural porcine surfactant inhibits superoxide anions and
      proinflammatory mediators released by resting and stimulated human monocytes.
AB  - Pulmonary surfactant has a potential role in modulating inflammation in normal
      and injured lungs. In lung injury, monocytes become activated and participate in
      lung inflammation. We therefore, investigated the proinflammatory functions of
      stimulated human blood monocytes after an overnight preincubation period with
      modified natural porcine surfactant (Curosurf) (500-1000 micrograms/mL).
      Monocytes were stimulated either with phorbol myristate acetate (PMA), bacterial
      extract OM-85, lipopolysaccharide (LPS), or Ca2+ ionophore A23187. The present
      study shows that Curosurf significantly inhibits: 1) the production of superoxide
      anions stimulated with OM-85 (1 mg/mL, 30 min), but not with PMA (100 ng/mL, 30
      min); 2) the release of cyclooxygenase metabolites prostaglandin E2 and
      thromboxane B2 stimulated with OM-85 (1 mg/mL, overnight); 3) the release of
      lipoxygenase metabolite leukotriene C4 stimulated with A23187 (10 microM, 10
      min); 4) the release of the cytokine TNF-alpha stimulated overnight with either
      OM-85 (1 mg/mL) or LPS (10 micrograms/mL)) in a dose-dependent fashion. In
      addition, Curosurf decreases the spontaneous adherence of monocytes to plastic
      culture wells in a dose-dependent fashion. Experiments performed with
      staurosporine, an inhibitor of protein kinase C (PKC) indicate that, in contrast
      with PMA, the production of superoxide anions stimulated by OM-85 is not related
      to PKC activation. Consequently, we propose that the mechanism involved in the
      suppressive effects of Curosurf is PKC-independent. In summary, the present study
      provides experimental evidence that favors the anti-inflammatory role of modified
      natural porcine surfactant (Curosurf) in human monocytes in vitro.

PMID- 8979300
TI  - Disease severity is correlated with plasma clotting and fibrinolytic and kinin
      kallikrein activity in neonatal respiratory distress syndrome.
AB  - This study was undertaken to determine whether simultaneous activation of
      clotting, fibrinolysis, and kinin-kallikrein is associated with disease severity
      in preterm infants with neonatal respiratory distress syndrome (RDS), during the
      first 5 d of life. In the infants with severe RDS, we found activation of
      clotting, fibrinolysis, and kinin-kallikrein within 6-12 h of birth, indicated by
      increased thrombin-antithrombin III complex formation [22.5 ng/ml versus 1.4
      ng/ml (median values) in the mild/moderate RDS infants, p < 0.001], increased
      tissue-type plasminogen activator plasma concentrations [5.1 ng/ml versus 2.6
      ng/ml (median values) in the mild/moderate RDS infants, p < 0.01], and increased
      plasma kallikrein activity [198% versus 189% of maximal activated human plasma
      (median values) in the mild/ moderate infants, p < 0.01], respectively. Thrombin
      generation, tissue-type plasminogen activator release, and kallikrein activity
      did not change significantly in the severe RDS group throughout the study. In
      these infants, kallikrein activity was accompanied by lower values of plasma
      kallikrein inhibitory activity. Activation of clotting, fibrinolysis, and kinin
      kallikrein was accompanied with a transient decrease of the neutrophil count and
      a steady decrease of the platelet count in the severe RDS group. The studied
      parameters of clotting and fibrinolytic and kinin-kallikrein activation were
      significantly correlated with continuous measures of RDS severity. We, therefore,
      suggest that this activation process likely contributes to respiratory
      insufficiency in neonatal RDS.

PMID- 8979301
TI  - Prenatal contact with inhalant allergens.
AB  - Pollen contact in early infancy may enhance the risk for subsequent pollen
      allergy. In this study likelihood of a prenatal antigen contact, as a result of
      inhalation of pollen allergens by the mother, was investigated. Due to the
      seasonal occurrence of allergens studied, the date of priming can be estimated,
      and this can supply data about the maturation of the fetal immune system.
      Proliferative responses of umbilical cord blood mononuclear cells (UCB MNCs) to
      the recombinant major allergens of birch (rBet v 1) and timothy grass (rPhl p 1)
      were analyzed throughout the whole year. A positive proliferative response was
      regarded as the criterion for a prenatal contact of the immune system with the
      allergen. Prenatal priming with both allergens was observed. Timothy grass pollen
      displayed considerably higher antigenicity than did birch pollen. The
      susceptibility of the fetal immune system to be primed by these allergens varies
      during the gestation period. The majority of positive responses to rPhl p 1 and
      rBet v 1 were found in UCB samples in which antigen contact (the respective
      pollen season) took place in the first 6 mo of pregnancy. Our results offer
      indirect evidence that, shortly after migration of T cell precursors to the
      epithelial thymus, T cells are mature enough for priming with antigens. No
      relationship was found between the susceptibility of the fetal immune system to
      be primed by these allergens and the clinical history of the family concerning
      type I allergy.

PMID- 8979302
TI  - Glucose production and gluconeogenesis are negatively related to body weight in
      mechanically ventilated, very low birth weight neonates.
AB  - The regulation of gluconeogenesis by low birth weight infants remains poorly
      delineated. To investigate this, 15 5-d-old infants (26-31-wk gestational age,
      795-1485-g body weight), were infused i.v. for 4 h with uniformly labeled [U
      13C]glucose (5 mg/kg/min) as the sole source of glucose. Intralipid (3 mg/kg/
      min) was provided, but no amino acids were given. Blood samples were taken
      immediately before and after 4 h of tracer infusion. The isotopic enrichments of
      plasma glucose and alanine were measured by selected ion monitoring gas
      chromatography mass spectrometry. Glucose production rates were calculated from
      the isotopic dilution of plasma [U-13C]glucose and the glucose infusion rate.
      Gluconeogenesis was estimated from the relative isotopic enrichments of [M + 3]-
      and [M + 6]-glucose, using the isotopic enrichment of plasma [U-13C]alanine, to
      define the isotopic dilution of the 3-carbon pool, and previously published
      equations to calculate the isotopic dilution of hepatic oxaloacetate. Glucose
      production (15 +/- 9 mumol/kg/min) was negatively related to body weight (r = 
      0.67; p < 0.05) and the ratio of the isotopic enrichments of
      [13C3]alanine:[13C6]glucose (0.27 +/- 0.07) was positively related to body weight
      (r = 0.74; p < 0.025). Both relationships were exponential. Gluconeogenesis (via
      pyruvate) accounted for 72 +/- 28% of glucose production, and gluconeogenesis per
      unit body weight was negatively and exponentially (r = -0.82; p < 0.005) related
      to body weight. These results demonstrate that neonates whose birth weights are
      less than 1200 g have a particularly high glucose production rate secondary to
      enhanced gluconeogenesis. We speculate that these results reflect a high weight
      specific glucose demand that is met by up-regulation of gluconeogenesis.

PMID- 8979303
TI  - Comparison of face mask, head hood, and canopy for breath sampling in flow
      through indirect calorimetry to measure oxygen consumption and carbon dioxide
      production of preterm infants < 1500 grams.
AB  - Complete sampling of expired air is essential for accurate O2 consumption(CO2
      production) [VO2(VCO2)] measurements with flow-through indirect calorimetry. In
      preterm infants complete sampling is critical, because only low sampling flows
      can be used. The accuracy of the various breath sampling systems at low flows and
      their patient compatibility is untested. We therefore measured 1) the accuracy of
      VO2(VCO2) measurements with a face mask, a head hood, and a canopy in vitro at
      low sampling flows; 2) the effect of breathing on measurements with the face
      mask; and 3) the effect of breath sampling systems on activity and body
      temperature of preterm infants. VO2(VCO2) were measured with a Deltatrac II. In
      vitro we used a methanol miniburner incorporated into a doll, which could
      simulate low VO2(VCO2) and tidal breathing. In vivo we studied seven preterm
      infants < 1500 g. With the face mask VO2(VCO2) measurements were accurate at a
      flow of 3 L/min (error -1 +/- 0.8%), when tidal volume was < 15 mL/breath and the
      distance between mask and manikin < 1 cm. With hood and canopy VO2(VCO2) were
      underestimated at a flow of 3 L/min (error -13 +/- 1% and -14 +/- 5%), and
      results were markedly influenced by body position. For accurate measurements, the
      hood needed a flow of 4.5 L/min, the canopy 8.3 L/min. In vivo the face mask did
      not increase heart rate, respiration, activity, or rectal temperature, but hood
      and canopy increased rectal temperature by 0.3-0.4 degree C. For VO2(VCO2)
      measurements in infants < 1500 g, a face mask should be used, which is accurate
      at low flows and does not change body temperature. Accuracy at low flows and
      patient compatibility of breath sampling systems should be evaluated and reported
      for VO2(VCO2) measurements in preterm infants.

PMID- 8979304
TI  - Methionine and serine formation in control and mutant human cultured fibroblasts:
      evidence for methyl trapping and characterization of remethylation defects.
AB  - The conversion of labeled formate to methionine and serine, as a measure of
      remethylation of homocysteine to methionine and folate coenzyme cycling, has been
      studied in control and mutant human fibroblasts. Fibroblasts in monolayer culture
      were incubated with [14C]formate, and labeled methionine sulfone and serine were
      determined in hydrolysates of oxidized cell proteins. In control cells,
      methionine and serine were clearly measurable (n = 21, 1.7-5.5 and 2.4-9.7
      nmol/mg protein/16 h, respectively). In contrast, methionine formation was
      reduced in cells from patients with methylenetetrahydrofolate reductase (MR)
      deficiency (MR mutant, n = 11, 0.05-0.44), combined methylmalonic
      aciduria/homocystinuria [cobalamin(cbl)C/D mutant, n = 12, 0.014-0.13), and
      methionine synthase deficiency (MS mutant, n = 3, 0.04-0.23). Furthermore, serine
      formation was low in cblC/D mutant (0.08-0.98) and MS mutant (0.17-0.94) cells,
      but normal or high in MR mutant cells (5.2-11.4). Growth of cblC/D mutant cells
      in medium supplemented with high concentrations of hydroxo-cbl resulted in
      significant increases of both methionine and serine formation. Taken together
      these findings provide clear evidence for the existence of the formate to serine
      pathway described by W. B. Strong and V. Schirch in cultured fibroblasts and
      indicate that disturbed MS function due to a specific genetic disorder is
      associated with reduced serine formation in vitro, which reflects availability of
      reduced folate coenzymes. The correction of this defect by vitamin B12 alone, in
      cblC/D mutant cell lines, correlates well with the clinical response in the
      patients and fits in well with the idea that reduced availability of folate
      coenzymes occurs in functional MS deficiency, in agreement with the methyl trap
      hypothesis.

PMID- 8979305
TI  - Interaction between nitric oxide and prostaglandin synthesis in the acute phase
      of allergic conjunctivitis.
AB  - Both nitric oxide and prostaglandins induce vasodilatation which is an important
      feature of local inflammation. The purpose of the study described here was to
      investigate a possible interaction between these two types of mediators in an
      experimental model of allergic conjunctivitis. A conjunctival allergic reaction
      was induced with antigen in sensitized guinea pigs. Conjunctival vascular
      permeability changes were evaluated with the prophylactic use of an inhibitor of
      nitric oxide synthase (L-NAME) and a cycloxygenase inhibitor (indomethacin). To
      study a possible interaction between nitric oxide and prostaglandin synthesis in
      the acute phase of allergic conjunctivitis, the levels of nitrite and PGE2 were
      determined in lavage fluid. The prophylactic use of L-NAME on the formation of
      conjunctival edema in response to topical PGD2 administration was studied by
      measurement of albumin levels in lavage fluid. Both nitric oxide and PGE2 are
      synthesized in response to antigen provocation and after histamine
      administration. Nitric oxide and PGE2 are produced simultaneously in the
      conjunctiva and they showed identical synthesis profiles in response to antigen
      provocation. Pretreatment with L-NAME inhibited the synthesis of PGE2 whereas
      exogenous administration of nitric oxide increased the level of PGE2 in lavage
      fluid. Prophylactic treatment with L-NAME significantly inhibited the PGD2
      induced albumin extravasation. Nitric oxide seems to play an important role in
      the acute phase of allergic conjunctivitis it may stimulate PGE2 production and
      acts as a secondary mediator in PGD2 and histamine induced conjunctival edema.

PMID- 8979306
TI  - Cysteinyl leukotrienes do not mediate lipopolysaccharide-induced airway
      hyperresponsiveness in guinea pigs.
AB  - Inhalation of bacterial lipopolysaccharide (LPS) by guinea pigs caused bronchial
      hyperreactivity to acetylcholine with a peak at 2 hr after exposure. Exposure to
      0.01% LPS for 30 min resulted in an elevation of cysteinyl leukotrienes (cys-LTs)
      content in bronchoalveolar lavage fluid (BALF) which was obtained 1 hr after LPS
      exposure. The cys-LTs antagonist, ONO-1078 (10 mg/kg, p.o.), significantly
      inhibited LPS-induced bronchial hyperreactivity, but ICI-204,219 (10 mg/kg,
      p.o.), another cys-LT antagonist, did not. Each dose employed in the present
      study was sufficient to inhibit LTD4-induced broncho-constriction in guinea pigs.
      In order to investigate the inhibitory mechanism of ONO-1078, the effect on the
      LPS-induced production of tumor necrosis factor (TNF) was examined. The amount of
      TNF in BALF increased significantly 2 hr after exposure to LPS. The inhalation of
      murine recombinant TNF-alpha (5 x 10(4) u/ml) resulted in bronchial
      hyperreactivity in guinea pigs. ONO-1078 (10 mg/kg, p.o.) inhibited the increase
      of LPS-induced TNF in BALF, but ICI-204,219 (10 mg/kg, p.o.) had no effect. These
      results suggest that TNF plays an important role in the onset of LPS-induced
      bronchial hyper-reactivity, and that ONO-1078 inhibits the LPS-induced airway
      hyperreactivity probably due to the inhibition of TNF production.

PMID- 8979307
TI  - Regulation of COX-2 gene expression in rat uterus in vivo and in vitro.
AB  - Prostaglandins are involved in mediating several important processes in mammalian
      reproduction, including the initiation of parturition. In the present study, we
      examined the expression in the rat uterus of two-rate limiting enzymes involved
      in prostaglandin production, cyclooxygenase (COX) 1 and 2. Expression of the COX
      2 gene in the pregnant rat uterus gave rise to a single mRNA transcript of
      approximately 4.4 kb. COX-2 mRNA levels increased 3.5 fold between day 7 of
      pregnancy and the onset of parturition on day 22. In contrast, COX-1 mRNA levels
      remained constant during the same period. To investigate factors involved in
      mediating the regulation of COX-1 and COX-2 gene expression, rat endometrial
      stromal and epithelial cell lines, were used. In the stroma-derived cell line,
      CUS-V2, COX-2 gene expression was demonstrated by reverse
      transcriptase/polymerase chain reaction (RT-PCR) and by immunocytochemistry. In
      these cells, COX-2 gene expression was inducible by the cytokines interleukin-1
      beta and tumor necrosis factor alpha, but not by interleukin-6. The two former
      cytokines also induced prostaglandin F2 alpha production. In contrast, COX-1 gene
      expression was constitutive in this cell line. In the endometrial epithelium
      derived cell line, CUE-P both COX-1 and COX-2 genes were expressed in a
      constitutive fashion. In conclusion, the present in vivo and in vitro data
      indicate that decidual COX-2, but not COX-1, gene expression is regulated during
      pregnancy and implicate specific cytokines as possible inducers within the
      decidua.

PMID- 8979308
TI  - Thromboxane A2 analogue contracts predominantly the hepatic veins in isolated
      canine liver.
AB  - Thromboxane A2 (TxA2) is a potent vasoconstrictor and has been implicated as a
      mediator of liver diseases such as ischemic-reperfusion injury. We determined the
      effects of TxA2 and the well-known hepatic venoconstrictor histamine, on the
      vascular resistance distribution and liver weight in isolated canine livers
      perfused with blood via the portal vein. The stable TxA2 (STA2; 20 micrograms, n
      = 5) and histamine (5 micrograms, n = 6) similarly increased the hepatic total
      vascular resistance, 2.5- and 2.4-fold, respectively. The increase in the hepatic
      venous resistance was significantly greater than that of the portal resistance
      (threefold vs. 1.9-fold for STA2; threefold vs. 1.8-fold for histamine).
      Predominant hepatic venoconstriction induced by both agents was confirmed in
      livers perfused in a reverse direction from the hepatic vein to the portal vein,
      as shown by marked precapillary vasoconstriction. STA2 transiently increased
      liver weight loss (-3.6 g/100 g liver weight), followed by a gradual weight gain
      (9.0 g/100 g). Histamine caused a progressive weight gain (9.1 g/100 g). In
      conclusion, similar to histamine, TxA2 constricts predominantly the hepatic vein
      in isolated canine livers.

PMID- 8979309
TI  - Differential effects of indomethacin on the sheep ovary: prostaglandin
      biosynthesis, intracellular calcium, apoptosis, and ovulation.
AB  - Cells of the apical wall of the dominant follicle and contiguous ovarian surface
      epithelium become apoptotic with the approach of ovulation in the sheep. It was
      hypothesized that indomethacin, an established inhibitor of prostaglandin
      biosynthesis and ovulation, would protect apical ovarian cells from programmed
      death. The anovulatory potencies of two systemic doses of indomethacin (200 and
      800 mg) were tested in gonadotropin-stimulated ewes. A complete blockade of
      ovulation occurred at the higher dose of indomethacin. Ovulation was not
      inhibited by 200 mg indomethacin. Both doses of drug suppressed follicular
      prostaglandin production below pregonadotropin levels. Immunofluorescence
      detection of digoxigenin end-labeled (fragmented) DNA was used as a marker of
      apoptosis among ovarian surface epithelial and granulosa cells recovered from the
      optical hemisphere of preovulatory ovine follicles. Cellular DNA fragmentation
      was averted in animals given 800 mg indomethacin, whereas apoptosis ensued after
      200 mg. A sustained increase in cytosolic calcium is generally a prerequisite to
      apoptotic DNA fragmentation and cell death. Indeed, intracellular calcium,
      detected by fluorescence of fura-2, was elevated in ovarian cells of animals
      destined to ovulate (controls, 200 mg indomethacin) in comparison to
      (safeguarded) cells of anovulatory ewes (800 mg indomethacin). These observations
      provide circumstantial evidence that apical ovarian cell degeneration by calcium
      mediated apoptosis is a determinant of follicular instability and rupture, but
      that these events are unrelated to the gonadotropin-induced rise in prostanoid
      production characteristic of preovulatory follicles.

PMID- 8979310
TI  - Anatomy, physiology, and development of feeding.
AB  - Dysphagia in infants and children is usually only one part of a broad spectrum of
      complex medical, health, and developmental problems. As etiologies vary, so do
      prognoses. Increased survival rates of infants in recent years have been
      accompanied by an increased prevalence of neurologic, cardiorespiratory, and
      structural impairments that can affect nutritional status and feeding function.
      Knowledge of anatomy, physiology, and normal development of feeding skills is
      basic to the assessment and management of pediatric dysphagia.

PMID- 8979311
TI  - Neurodevelopmental presentation of dysphagia.
AB  - Successful oral feeding and growth of infants and children are dependent not only
      on functional deglutition, but also on a broad range of neurodevelopmental skills
      involving sensory systems, cognition/communication, and gross and fine motor
      behaviors. Children with neurogenic dysphagia often have a broad spectrum of
      neurodevelopmental impairments that affect these streams of development.
      Speech/language pathologists, as members of interdisciplinary teams, can provide
      unique contributions to the early diagnosis and management of neurogenic
      dysphagia in childhood.

PMID- 8979312
TI  - Dysphagia in infants and children with oral-motor deficits: assessment and
      management.
AB  - Speech-language pathologists who are feeding specialists take an active role in
      the evaluation and management of infants and children with dysphagia and oral
      motor deficits. This article focuses on those infants and children who have
      feeding difficulties due to respiratory, neurologic, anatomic, and/or
      gastointestinal disorders in the NICU or hospital setting and after their
      discharge to home. Evaluation and treatment techniques emphasizing clinical
      management are described. Assessment of behavioral state, passive positioning and
      dynamic handling, utensil selection, bolus modification, compensatory techniques,
      and oral/nonoral feedings are discussed. Involvement of the family is considered
      a critical part of all team interventions.

PMID- 8979313
TI  - Specialized studies in pediatric dysphagia.
AB  - The evaluation and management of the pediatric patient with a feeding and
      swallowing disorder may require the use of specialized studies to evaluate
      specific aspects of swallowing function; to judge the consequences of the
      swallowing dysfunction; and to assess factors that may be contributing to
      swallowing dysfunction. Instrumental assessment of swallowing function may
      include upper gastrointestinal studies, videofluoroscopy or videofluoroscopic
      swallow studies, ultrasonography, radionuclide imaging, fiberoptic endoscopy of
      swallowing, and cervical auscultation. Procedures that assess the consequences
      and/or identify factors contributing to swallowing dysfunction may include pulse
      oximetry, chest x-rays, laryngoscopy and/or bronchoscopy, and pulmonary function
      tests. The use of such specialized procedures to evaluate children with dysphagia
      is the focus of this article.

PMID- 8979314
TI  - Development of the lumbar and sacral vertebral canal in utero.
AB  - STUDY DESIGN: This study analyzed the development of the lumosacral vertebral
      canal and dural sac in human fetus. A collection of fetuses and embryos was used
      to assess the development of different parameters of the spinal canal.
      OBJECTIVES: The data were analyzed for the dynamics of the development and also
      compared with mean adult spinal parameters. SUMMARY OF BACKGROUND DATA:
      Transversely sectioned specimens and nonsectioned specimens free of abnormalities
      were selected from the Boyd Collection of human embryos and fetuses. METHODS: The
      sections were photographed alongside a micrometric scale, and the nonsectioned
      specimens were scanned by magnetic resonance imaging. The films were computer
      analyzed for spinal and dural parameters. The error of the measurements was
      assessed. RESULTS: The most rapid growth period of the spinal canal parameters is
      between 18-36 weeks' gestation. After 30 weeks of intrauterine life, the upper
      lumbar canal grows faster than the lower lumbar region. The distal end of the
      dural sac begins to rise from S5 after 14 weeks. CONCLUSIONS: At the end of
      intrauterine growth, the interpedicular diameter of the spinal canal from L1 to
      L4 is 70% of the adult size, however, at L5, the canal is only 50% mature at
      birth. Therefore, if there is growth impairment in early infancy, the upper
      lumbar region is partially protected in contrast with the L5 level.

PMID- 8979315
TI  - Anatomic considerations for posterior approach to the sacroiliac joint.
AB  - STUDY DESIGN: This anatomic study describes a new intraosseous, posterior
      approach to the sacroiliac joint. OBJECTIVES: To define a transosseous approach
      to the sacroiliac joint in which a triangular bony window is raised on the
      posterosuperior aspect of the ilium that provides improved access to the
      sacroiliac joint for posterior fusion. SUMMARY OF BACKGROUND DATA: A posterior
      approach to the sacroiliac joint has been widely used for debridement of
      infectious diseases and for fusion. Most conventional approaches to the
      sacroiliac joint are interosseous, and there is a relative lack of information on
      transiliac approaches. METHODS: The projection of the sacroiliac joint on the
      outer table of the ilium and the thickness of the posterior ilium forming part of
      the sacroiliac joint were determined in 15 cadaveric pelves. A right angle,
      triangular bony window was raised from the posterior ilium to investigate the
      suitability of a transiliac approach in performing sacroiliac debridement and
      arthrodesis. A horizontal reference line 3-3.5 cm in length was drawn between a
      point 1 cm anterosuperior to the posteroinferior iliac spine and a point 1.5 cm
      superior to the superior border of the greater sciatic notch. A vertical
      reference line was extended superiorly for 2-2.5 cm perpendicular to and
      beginning at the anterior end of the horizontal reference line. The oblique arm
      of the right triangle was created by joining the superior end of the vertical
      reference line to the posterior end of the horizontal line. RESULTS: Thirty
      percent to fifty percent of the articular surface of the iliac bone was removed
      with this triangular segment of bone, and a corresponding area of the sacral
      articular surface was visualized directly. It was possible to remove the rest of
      the articular cartilage with angled curettes in all specimens. CONCLUSIONS: This
      approach facilities improved access to the sacroiliac joint for debridement and
      arthrodesis with minimal soft tissue dissection and iliac bone resection.

PMID- 8979316
TI  - Ceramic anterior spinal fusion. Biologic and biomechanical comparison in a canine
      model.
AB  - STUDY DESIGN: Three types of porous ceramic bone graft substitutes were used for
      anterior interbody fusion in the canine thoracic spine. OBJECTIVES: To compare
      the biomechanical stiffness and histologic appearance of fused spinal segments
      using ceramic graft substitutes versus autogenous bone graft. SUMMARY OF
      BACKGROUND DATA: The relative success or failure of ceramic grafts is influenced
      by many variables, including the composition of the ceramic, location in the
      spine, stability, and the animal model used. METHODS: Four experimental groups
      were evaluated: autogenous tricortical iliac crest (n = 6); hydroxyapatite
      ceramic (Interpore-200; n = 6); biphasic (60 : 40) hydroxyapatite/tricalcium
      phosphate ceramic (Zimmer; n = 4); and calcium carbonate ceramic (Inoteb; n = 4).
      All dogs were killed 8 weeks after surgery. After postmortem removal of anterior
      spinal instrumentation, the spinal segments underwent nondestructive
      biomechanical testing and light microscopic histologic evaluation. RESULTS:
      Biomechanical testing showed that spines from the autogenous tricortical iliac
      crest group were statistically significantly stiffer in flexion, extension, left
      and right bending, and torsion than all ceramic groups. No differences in
      stiffnesses were observed among the three ceramic groups. Histologically, the
      autogenous tricortical iliac crest graft performed best, with osseous union at 10
      of 12 interfaces. Of the ceramic grafts, hydroxyapatite/tricalcium phosphate and
      calcium carbonate demonstrated more consistent junction healing than the
      hydroxyapatite group, where four of 12 interfaces resulted in a nonunion. In the
      ceramic groups, a variable amount of revascularization and new bone was observed
      within the grafts. CONCLUSIONS: Autogenous iliac crest bone graft provides
      superior healing in this anterior spine fusion model. Additional investigation is
      needed before ceramic grafts can be considered satisfactory alternatives to
      anterior autogenous bone grafts.

PMID- 8979317
TI  - New insight into the mechanics of the lumbar interspinous ligament.
AB  - STUDY DESIGN: Repeated in vitro mechanical tests were performed on porcine and
      human interspinous ligament specimens with progressive disruption of the collagen
      fiber network to evaluate the existence of mechanical interactions between
      collagen fibers. OBJECTIVE: To evaluate the existence of a load pathway in the
      interspinous ligament whereby loads are transmitted between collagen fibers.
      SUMMARY OF BACKGROUND DATA: Mechanical tests demonstrate that the interspinous
      ligament resists spinal flexion, but the collagen fibers are not oriented to
      oppose separation of the spinous processes. This seeming contradiction could be
      explained by the existence of mechanical interactions between collagen fibers of
      the interspinous ligament. METHODS: In vitro mechanical tests were performed on
      porcine and human bone-interspinous ligament-bone specimens. The collagen network
      of the ligament substance was disrupted by passing a scalpel blade though the
      ligament substance. Repeated tests were performed with progressive disruption of
      the collagen fiber network. RESULTS: The stiffness of the interspinous ligament
      specimens was reduced as the collagen fiber network was disrupted, but
      approximately half of the initial stiffness was maintained when the collagen
      fiber network was severely disrupted. In this case, no intact collagen fibers
      remained. CONCLUSIONS: Mechanical interactions exist between collagen fibers in
      the interspinous ligament. The mechanism of the interactions is unknown.

PMID- 8979318
TI  - Comparison between single-screw and triangulated, double-screw fixation in
      anterior spine surgery. A biomechanical test.
AB  - STUDY DESIGN: The advantage to fixation strength of triangulated, double-screw
      fixation compared with that of single-screw instrumentation in anterior spine
      surgery was evaluated by in vitro testing. OBJECTIVES: To compare the fixation
      strength of single-screw instrumentation with ventral derotation spondylodesis
      screws with the fixation strength of triangulated, double-screw instrumentation
      with Cotrel-Dubousset-Hopf screws. Resistance against pull-out load and against
      load perpendicular to the axis of the screws was evaluated. To avoid the bias
      caused by different screw design, the pull-out strength of single screws of both
      devices was compared first. SUMMARY OF BACKGROUND DATA: To the authors'
      knowledge, no study comparing anterior single with triangulated screws has been
      published. METHODS: A pull-out test was performed when one vertebra in each spine
      specimen was instrumented with a ventral derotation spondylodesis screw, one with
      an isolated Cotrel-Dubousset-Hopf screws, and one with two triangulated, Cotrel
      Dubousset-Hopf screws linked by a Cotrel-Dubousset-Hopf block. Load perpendicular
      to the axis of the screw was applied on the bone-device interface after
      instrumentation of further specimens with ventral derotation spondylodesis and
      triangulated, Cotrel-Dubousset-Hopf devices. RESULTS: Use of isolated Cotrel
      Dubousset-Hopf screws compared with ventral derotation spondylodesis screws
      showed no significant differences in pull-out strength. The use of triangulated,
      double-screw fixation with Cotrel-Dubousset-Hopf screws led to a significant 79%
      increase in resistance against pull-out and a 73% increase in resistance against
      load perpendicular to the screw axis compared with the resistance produced using
      ventral derotation spondylodesis single-screw instrumentation. CONCLUSION: In
      anterior surgery, fixation of the vertebra-device interface can be improved
      considerably by application of two triangulated screws.

PMID- 8979319
TI  - The nosologic status of the whiplash syndrome: a critical review based on a
      methodological approach.
AB  - STUDY DESIGN: Empirical studies concerning the whiplash syndrome are reviewed
      from the point of view of epidemiologic methodology. OBJECTIVE: To assess the
      nosologic status of the whiplash syndrome. SUMMARY OF BACKGROUND DATA: Although a
      large number of studies concerning the syndrome exist, there is still controversy
      concerning the existence of the syndrome. METHODS: The manner in which each study
      contributes to the validity of the syndrome is determined on the basis of the
      methodologic design (descriptive, case-control, cohort, and
      intervention/experimental) of the study. RESULTS: Whereas the face validity of
      the syndrome is excellent, the descriptive, construct, and predictive validity
      are rather poor. In particular, convincing empirical evidence for a causal link
      (construct validity) between the trauma mechanism and chronic symptoms is sparse.
      CONCLUSIONS: Carefully conducted studies designed to assess the degree to which
      head and nec trauma contribute to the development of chronic pain, particularly
      head and neck pain, are urgently needed.

PMID- 8979320
TI  - A cross-sectional study correlating cervical radiographic degenerative findings
      to pain and disability.
AB  - STUDY DESIGN: A cross-sectional design was used to correlate cervical
      radiographic findings of spinal degeneration to neck pain and disability.
      OBJECTIVES: The results were correlated to assess the clinical importance of
      radiographic spinal degeneration. SUMMARY OF BACKGROUND DATA: Past investigations
      suggest little association between clinical findings and radiographic evidence of
      spinal degeneration. However, changes in activities of daily living and
      chronicity of complaint have not been investigated. METHODS: Over a 5-month
      period, data were collected on 700 consecutive patients referred for cervical
      radiographic examination as part of their clinical evaluation. While in the
      radiology department, all subjects completed a visual analog pain scale, neck
      disability index, and short questionnaire, all of which quantified various
      aspects of any neck complaint. Relationships between indices of patient complaint
      and the number of cervical degenerative intervertebral discs were evluated using
      regression analysis. RESULTS: A significant relationship (P < 0.001) was noted
      between the number of levels of intervertebral disc degeneration and the
      chronicity of cervical complaint. No significant relationship was found between
      cervical degeneration and past trauma (P = 0.904) or gender (P = 0.213). Multiple
      regression analysis of visual analog pain scale scores revealed a significant two
      way interaction with chronicity and past trauma (P = 0.007) and a significant
      main effect with gender (P < 0.001). Cervical degeneration was not significant as
      a main effect or interaction with other factors. Multiple-regression analysis of
      neck disability index scores demonstrated a significant three-way interaction of
      chronicity, degeneration, and gender (P = 0.022) and a significant two-way
      interaction for chronicity and trauma (P = 0.025). No additional information was
      gathered by multivariate multiple-regression techniques. CONCLUSIONS: Increasing
      levels of spinal degeneration are related to increasing chronicity of patient
      complaints. Spinal degeneration is not related to past trauma or gender. Women,
      but not men, report higher disability with increasing levels of degeneration.
      Subjects with past trauma reported more intense pain and disability. Overall, men
      reported less neck pain and disability than women.

PMID- 8979321
TI  - Migration of the nucleus pulposus within the intervertebral disc during flexion
      and extension of the spine.
AB  - STUDY DESIGN: Magnetic resonance images were obtained of the lumbar spines of
      three volunteers in neutral, flexed, and extended postures. OBJECTIVES: To
      measure migration of the nucleus pulposus within the intervertebral disc during
      flexion and extension of the spine in living people. SUMMARY OF BACKGROUND DATA:
      Results of experiments on bisected cadaveric spines have indicated that the
      nucleus migrates posteriorly during flexion and anteriorly during extension in
      nondegenerate discs. Degenerate discs may have faults or fissures that result in
      abnormal motion of the nucleus. METHODS: Proton density weighted, sagittal,
      magnetic resonance images were obtained from the lumbar spines of three
      volunteers. Measurements of the positions of the anterior and posterior margins
      of the nucleus and of flexion and extension angles were made on tracings of the
      images corresponding to neutral, flexed, and extended postures. RESULTS: The
      observed frequency (22 of 24 measurements) at which the margins of the nucleus
      migrated in the directions predicted by results of cadaveric studies was
      significantly greater than the frequency that would be expected by chance (P <
      0.001). The two exceptions may be a result of disc degeneration. There was a
      significant (P < 0.05) linear correlation between the migration of the anterior
      margin and the flexion-extension angle and a highly significant (P < 0.001)
      correlation for the posterior margin and the flexion-extension angle.
      CONCLUSIONS: Flexion of an intervertebral disc in a living person tends to be
      accompanied by posteriorly directed migration of the nucleus pulposus within the
      disc. Extension tends to be accompanied by an anteriorly directed migration.

PMID- 8979322
TI  - The prolapsed intervertebral disc. The high-intensity zone with discography
      correlation.
AB  - STUDY DESIGN: The study compared the presence of the high-intensity zone on
      magnetic resonance imaging with the results of awake discography. OBJECTIVES: To
      see if there was a correlation between the results of awake discography and the
      presence of a high-intensity zone on magnetic resonance imaging. SUMMARY OF
      BACKGROUND DATA: The evaluation of discogenic pain has proved to be somewhat
      elusive. Recent studies have indicated the high-intensity zone as being highly
      sensitive in the diagnosis of the painful discogenic segment. The present study
      was designed to investigate whether the presence of a high-intensity zone is
      associated with a concordant pain response on awake discography. METHODS:
      Magnetic resonance images were obtained in 29 patients with low back pain with
      and without radiculopathy. Consecutive patients were considered for surgical
      intervention after falling to respond to conservative treatment. The presence of
      a high-intensity zone was specifically looked for within the posterior anulus.
      Each patient subsequently underwent awake discography with computed tomography.
      Computed tomography was classified according to the Dallas Discogram Scale and
      the presence of a concordant pain response. Chi-square analysis was used to
      calculate the presence of a high-intensity zone versus disc disruption and the
      correlation of high-intensity zone and concordant pain response. RESULTS: There
      was no statistically significant correlation between the presence of a high
      intensity zone and a concordant pain response at any level. The high-intensity
      zone was, however, never seen in a morphologically normal disc. CONCLUSIONS:
      Although the high-intensity zone is present within the posterior anulus of some
      abnormal discs, it is not necessarily associated with a concordant pain response.

PMID- 8979323
TI  - Multifidus muscle recovery is not automatic after resolution of acute, first
      episode low back pain.
AB  - STUDY DESIGN: A clinical study was conducted on 39 patients with acute, first
      episode, unilateral low back pain and unilateral, segmental inhibition of the
      multifidus muscle. Patients were allocated randomly to a control or treatment
      group. OBJECTIVES: To document the natural course of lumber multifidus recovery
      and to evaluate the effectiveness of specific, localized, exercise therapy on
      muscle recovery. SUMMARY OF BACKGROUND DATA: Acute low back pain usually resolves
      spontaneously, but the recurrence rate is high. Inhibition of multifidus occurs
      with acute, first-episode, low back pain, and pathologic changes in this muscle
      have been linked with poor outcome and recurrence of symptoms. METHODS: Patients
      in group 1 received medical treatment only. Patients in group 2 received medical
      treatment and specific, localized, exercise therapy. Outcome measures for both
      groups included 4 weekly assessments of pain, disability, range of motion, and
      size of the multifidus cross-sectional area. Independent examiners were blinded
      to group allocation. Patients were reassessed at a 10-week follow-up examination.
      RESULTS: Multifidus muscle recovery was not spontaneous on remission of painful
      symptoms in patients in group 1. Muscle recovery was more rapid and more complete
      in patients in group 2 who received exercise therapy (P = 0.0001). Other outcome
      measurements were similar for the two groups at the 4-week examination. Although
      they resumed normal levels of activity, patients in group 1 still had decreased
      multifidus muscle size at the 10-week follow-up examination. CONCLUSIONS:
      Multifidus muscle recovery is not spontaneous on remission of painful symptoms.
      Lack of localized, muscle support may be one reason for the high recurrence rate
      of low back pain following the initial episode.

PMID- 8979324
TI  - Trunk extensor and flexor strength measured by the Cybex 6000 dynamometer.
      Assessment of short-term and long-term reproducibility of several strength
      variables.
AB  - STUDY DESIGN: Isokinetic trunk extensor and flexor strength (peak torque, total
      work, power acceleration time, and torque acceleration energy) at 30 degrees/sec,
      120 degrees/sec, and 180 degrees/sec and isometric extensor and flexor peak
      torque were measured in 24 healthy women. Measurements were performed in three
      separate sessions at the same time of day and by the same experienced examiner.
      The number of days between Session 1 and Session 2 and between Session 1 and
      Session 3 ranged from 1 to 7 (median, 2 days) and from 23 to 48 (median, 32
      days), respectively. The test results were not revealed before all sessions were
      completed. OBJECTIVES: To determine the intrasession, short-term, and long-term
      reproducibility of several trunk strength variables measured by the Cybex 6000
      isokinetic dynamometer (Lumex, Inc., Ronkonkoma, NY). SUMMARY OF BACKGROUND DATA:
      Only few and insufficient data regarding the reproducibility of trunk strength
      measurements exist. Previous studies have focused on coefficients of correlation
      to express reproducibility. Correlations, however, are misleading and
      inappropriate for this purpose. The critical difference is the difference between
      two results that would be statistically significant when applied to a reference
      group in steady state. The critical difference in percentage is calculated as
      2.77 X coefficient of variation (%). METHODS: Isokinetic dynamometry (Cybex
      6000). Reproducibility was expressed as pooled coefficients of variation,
      individual coefficients of variation, and critical differences. RESULTS:
      Substantial between-subject variation of coefficients of variation was found for
      all strength variables; for example, the 80% central range for individual
      coefficients of variation for long-term reproducibility of extensor strength
      measurements at 30 degrees/sec ranged from 2.5% to 19.5%. Critical differences
      calculated using the pooled variances for long-term reproducibility were higher
      than 20% for all measures, mounting to 80% for acceleration time. CONCLUSIONS:
      Strength testing is of limited value in the individual subject because of
      considerable day-to-day variability. This finding has important clinical
      implications.

PMID- 8979325
TI  - Regression of back and posterior pelvic pain after pregnancy.
AB  - STUDY DESIGN: A prospective, consecutive cohort analysis of the regression of the
      incidence and intensity of back and posterior pelvic pain after delivery in
      pregnant women was done. OBJECTIVE: To identify back and posterior pelvic pain
      from mid-pregnancy to 5 months after delivery and to illustrate differences
      between these two pain types. SUMMARY OF BACKGROUND DATA: Chronic back pain may
      start during a pregnancy, and regression of unspecified back pain after delivery
      may be slow and incomplete. Few studies have distinguished back pain from
      posterior pelvic pain in pregnancy, and no study has presented follow-up data
      after delivery with respect to pain types. METHODS: One hundred and sixty four of
      368 pregnant women studied had back or posterior pelvic pain and were offered
      individual group physiotherapy and training. The women were observed until 5
      months after delivery. Standardized clinical examination protocols and
      questionnaires were used. RESULTS: Posterior pelvic pain was experienced by 124
      women, and back pain was experienced by 40 women during pregnancy. After
      delivery, however, back pain was more common. Pain intensity was higher among
      women with posterior pelvic pain during pregnancy, whereas after delivery pain
      intensity was higher among women with back pain. A correlation was found between
      the presence of high pain intensity during pregnancy and little regression of
      pain after delivery. CONCLUSIONS: One of every three pregnant women studied
      experienced posterior pelvic pain, and one of every nine women experienced back
      pain. Posterior pelvic pain was more intense during pregnancy, and back pain was
      more intense and more common after delivery. High pain intensity in pregnancy
      indicated a bad prognosis.

PMID- 8979326
TI  - Self-reported physical exertion in geriatric care. A risk indicator for low back
      symptoms?
AB  - STUDY DESIGN: The study group consisted of 131 female nursing aides who took part
      in an intervention program with physical training or education. Assessments were
      performed before the intervention program and after 6 months. At follow-up
      evaluation, 91 nursing aides remained in the study. OBJECTIVES: To examine if
      perceived physical exertion was a risk indicator for low back symptoms, and to
      examine the relationship between perceived physical exertion, aerobic capacity,
      back endurance, psychological demands, and job control. SUMMARY OF BACKGROUND
      DATA: Perceived physical exertion frequently is assessed in epidemiologic studies
      concerning low back symptoms. More information about the relationship between
      perceived exertion, other potential risk indicators, and symptoms may provide
      opportunities for effective prevention of symptoms. METHODS: Assessments were
      obtained by questionnaires and physical capacity tests. RESULTS: The nursing
      aides who reported high physical exertion and were 45 years of age or older were
      at greater risk in the follow-up period for reporting new symptoms, continued
      symptoms with the same intensity, or more intense symptoms from the low back
      (rate ratio, 3.01; 95% confidence interval, 1.1-8.2). The exposure variable
      correlated most strongly (r = 0.4) with perceived physical exertion was
      psychological demands. CONCLUSIONS: The results indicated being aged 45 years or
      older, combined with high perceived physical exertion, was a risk indicator for
      low back symptoms. A relationship between perceived physical exertion and
      psychological demands was observed, but there was no influence of physical
      capacity on perceived physical exertion.

PMID- 8979327
TI  - Prospective, multicenter study of spinal cord stimulation for relief of chronic
      back and extremity pain.
AB  - STUDY DESIGN: This prospective, multicenter study was designed to investigate the
      efficacy and outcome of spinal cord stimulation using a variety of clinical and
      psychosocial outcome measures. Data were collected before implantation and at
      regular intervals after implantation. This report focuses on 70 patients who had
      undergone 1 year of follow-up treatment at the time of data analysis. OBJECTIVES:
      To provide a more generalizable assessment of long-term spinal cord stimulation
      outcome by comparing a variety of pain and functional/quality-of-life measures
      before and after management. This report details results after 1 year of
      stimulation. SUMMARY OF BACKGROUND DATA: The historically diverse methods,
      patient selection criteria, and outcome measures reported in the spinal cord
      stimulation literature have made interpretation and comparison of results
      difficult. Although short-term outcomes are generally consistent, long-term
      outcomes of spinal cord stimulation, as determined by prospective studies that
      assess multidimensional aspects of the pain complaint among a relatively
      homogeneous population, are not well established. METHODS: Two hundred nineteen
      patients were entered at six centers throughout the United States. All patients
      underwent a trial of stimulation before implant of the permanent system. Most
      were psychologically screened. One hundred eighty-two patients were implanted
      with a permanent stimulating system. At the time of this report, complete 1-year
      follow-up data were available on 70 patients, 88% of whom reported pain in the
      back or lower extremities. Patient evaluation of pain and functional levels was
      completed before implantation and 3, 6, 12, and 24 months after implantation.
      Complications, medication usage, and work status also were monitored. RESULTS:
      All pain and quality-of-life measures showed statistically significant
      improvement during the treatment year. These included the average pain visual
      analogue scale, the McGill Pain Questionnaire, the Oswestry Disability
      Questionnaire, the Sickness Impact Profile, and the Back Depression Inventory.
      Overall success of the therapy was defined as at least 50% pain relief and
      patient assessment of the procedure as fully or partially beneficial and
      worthwhile. Using this definition, spinal cord stimulation successfully managed
      pain in 55% of patients on whom 1-year follow-up is available. Complications
      requiring surgical intervention were reported by 17% (12 of 70) of patients.
      Medication usage and work status were not changed significantly. CONCLUSIONS:
      This prospective, multicenter study confirms that spinal cord stimulation can be
      an effective therapy for management of chronic low back and extremity pain.
      Significant improvements in many aspects of the pain condition were measured, and
      complications were minimal.

PMID- 8979328
TI  - Efficacy of autotransfusion in spine surgery: comparison of autotransfusion alone
      and with hemodilution and apheresis.
AB  - STUDY DESIGN: Two prospective groups of patients received intraoperative
      autologous transfusion during reconstructive spine surgery. Before intraoperative
      autologous transfusion, one group underwent normovolemic hemodilution and
      apheresis of blood components in the operating room while being prepared for
      surgery. The allogeneic blood products needed for transfusion by each group were
      studied and compared with those of a retrospective group of patients receiving
      conventional transfusion therapy. OBJECTIVES: To determine if a combination of
      intraoperative autologous transfusion and hemodilution and apheresis decreases
      reliance on allogeneic blood products and increases autologous transfusions.
      SUMMARY OF BACKGROUND DATA: Transfusion rates of allogeneic red blood cells,
      which were unchanged by intraoperative autologous transfusion alone, were lowered
      when treatment included transfusion of these cells and preoperative autologous
      deposit. However, donor exposures from transfusions of allogeneic platelets and
      fresh frozen plasma have not been addressed. METHOD: Preoperative hemodilution
      and apheresis of autologous red blood cells, fresh plasma, and platelets,
      performed during induction of anesthesia for spine surgery was followed by
      intraoperative autologous transfusion using the same supplies. Intra- and
      postoperative transfusion of blood products to each group were evaluated and
      compared; allogeneic transfusions were given to a retrospective cohort of
      patients who received conventional transfusion therapy. RESULTS: Hemodilution and
      apheresis followed by intraoperative autologous transfusion reduced exposures to
      individual blood donor products resulting in fewer transfusions and in
      transfusion of significantly fewer blood products. Intraoperative autologous
      transfusion alone decreased the number of red blood cells transfused, but
      required the same donor exposures for fresh frozen plasma and platelet support as
      the cohort of patients who received conventional transfusion therapy.
      CONCLUSIONS: A combination of hemodilution and apheresis and intraoperative
      autologous transfusion significantly decreased transfusion of allogeneic blood
      products and reliance on preoperative autologous deposit. Autologous transfusion
      of all blood products was significantly increased.

PMID- 8979329
TI  - Cervical pseudarthrosis in ankylosing spondylitis. A case report.
AB  - STUDY DESIGN: This report illustrates two different cases of cervical
      pseudarthrosis in ankylosing spondylitis. OBJECTIVES: To point out the extreme
      rarity of this condition at cervical level, to discuss the pathogenesis, and to
      stress the necessity of surgical management. SUMMARY AND BACKGROUND DATA:
      Pathogenesis of pseudarthrosis in ankylosing spondylitis is discussed. Several
      factors are involved: trauma, which may be major or minor and undetected; stress
      fracture; and inflammatory changes. Major trauma was the cause of pseudarthrosis
      in the first patient, whereas stress fracture and inflammatory changes were the
      probable causes in patient 2. In patient 1 there were signs and symptoms of cord
      compression. Patient 2 was referred because of functional disability resulting
      from kyphosis and because of potential neurologic risk. METHODS: Cervical fusion
      was performed in both patients. Patient 1 underwent posterior fusion; patient 2
      had combined fusion. Patient 1 also underwent a lamineotomy. RESULTS: The course
      of the disorder after surgery was uneventful in both patients. Neurologic
      symptoms subsided in patient 1; kyphosis was corrected in patient 2. Both
      patients resumed their preoperative activities. Follow-up evaluation was done 6
      years after surgery in patient 1 and 2 years after surgery in patient 2.
      CONCLUSIONS: Pseudarthrosis of the cervical spine in ankylosing spondylitis is
      extremely rare. Presentation of the two patients was different in terms of
      pathogenesis and signs and symptoms. Surgical treatment is advocated for this
      disorder.

PMID- 8979330
TI  - Spinal osteomyelitis presenting with a life-threatening pleural empyema.
AB  - STUDY DESIGN: This case report illustrates a rare presentation of spinal
      osteomyelitis that initially manifested as a life-threatening pleural empyema
      leading to misdiagnosis. OBJECTIVES: A high index of suspicion is required to
      make the correct diagnosis of spinal osteomyelitis, especially with unusual
      presentations. Appropriate antibiotic management should be commenced immediately
      the diagnosis is made. SUMMARY OF BACKGROUND DATA: A review of the literature
      reveals five previous cases of vertebral osteomyelitis associated with pleural
      effusions. In three of these, the effusions were reactive and sterile. There is
      only one previous case of a pleural empyema related to primary spinal
      osteomyelitis. There also is one case report of vertebral osteomyelitis
      presenting as a mediastinal abscess. METHODS: A case is presented of a man
      thought to have bronchogenic carcinoma with a destructive vertebral metastasis
      who was sent for palliative radiation therapy. A life-threatening pleural
      effusion subsequently developed, and after additional investigation, he was found
      to have spinal osteomyelitis with a pleural empyema. RESULTS: The empyema was
      drained through an indwelling chest tube, and the patient was administered
      appropriate antibiotics. He made a complete and uneventful recovery. CONCLUSIONS:
      The case illustrates a rare presentation of spinal osteomyelitis. It exemplifies
      the dictum that if a malignant disease is suspected, every effort has to be made
      to establish a histologic diagnosis to prevent inappropriate management and the
      potentially devastating consequences of an incorrect diagnosis. It also high
      lights the difficulties in diagnosis of vertebral osteomyelitis with empyema.
      With correct management, the prognosis is excellent.

PMID- 8979331
TI  - Exercise for osteoporosis--is walking enough? The case for site specificity and
      resistive exercise.
AB  - Historic and clinical references obtained by general literature review and a
      medlars search from 1984-1994 on the impact of muscle strengthening on bone
      mineralization were reviewed and analyzed. The efficacy of site-specific
      resistive exercise on bone mineral enhancement and/or preservation as a
      supplement to weight-bearing exercise is documented. Previous reports
      demonstrated that resistive exercises enhance bone mineralization and play an
      equivalent, or perhaps greater role, than weight-bearing activities in the
      management of osteoporosis.

PMID- 8979332
TI  - Use of sulfite and hydrogen peroxide to control bacterial contamination in
      ethanol fermentation.
AB  - Lactic acid bacteria isolated from an industrial-scale ethanol fermentation
      process were used to evaluate sulfite as a bacterial-contamination control agent
      in a cell-recycled continuous ethanol fermentation process. The viabilities of
      bacteria were decreased by sulfite at concentrations of 100 to 400 mg liter-1,
      while sulfite at the same concentrations did not change the viability of the
      Saccharomyces cerevisiae strain used in this process. Sulfite was effective only
      in the presence of oxygen. Bacteria showed differences in their susceptibilities
      to sulfite. Facultatively heterofermentative Lactobacillus casei 4-3 was more
      susceptible than was obligatory heterofermentative Lactobacillus fermentum 7-1.
      The former showed higher enzyme activities involved in the production and
      consumption of hydrogen peroxide than did the latter. The viability of L.
      fermentum 7-1 could be selectively controlled by hydrogen peroxide at
      concentrations of 1 to 10 mM. Based on these findings, it is hypothesized that
      the sulfur trioxide radical anions formed by peroxidase in the presence of
      hydrogen peroxide are responsible for the control of contaminating bacteria.
      Sulfite did not kill the yeast strain, which has catalase to degrade hydrogen
      peroxide. A cell-recycled continuous ethanol fermentation process was run
      successfully with sulfite treatments.

PMID- 8979333
TI  - Mitochondrial DNA loss caused by ethanol in Saccharomyces flor yeasts.
AB  - Saccharomyces flor yeasts proliferate at the surface of sherry wine, which
      contains over 15% (vol) ethanol. Since ethanol is a powerful inducer of
      respiration-deficient mutants, this alcohol has been proposed to be the source of
      the high diversity found in the mitochondrial genomes of flor yeasts and other
      wine yeasts. Southern blot analysis suggests that mitochondrial DNA (mtDNA)
      polymorphic changes are due to minor lesions in the mitochondrial genome. As
      determined in this work by pulsed-field gel electrophoresis, restriction
      analysis, and Southern blot analysis, ethanol-induced petite mutants completely
      lack mtDNA (rho zero). Ethanol-induced changes in the mitochondrial genome that
      could explain the observed mtDNA polymorphism in flor yeasts were not found. The
      transfer of two different mtDNA variants from flor yeasts to a laboratory strain
      conferred in both cases an increase in ethanol tolerance in the recipient strain,
      suggesting that mtDNAs are probably subjected to positive selection pressure
      concerning their ability to confer ethanol tolerance.

PMID- 8979334
TI  - Isolation, purification, and amino acid sequence of lactobin A, one of the two
      bacteriocins produced by Lactobacillus amylovorus LMG P-13139.
AB  - Lactobacillus amylovorus LMG P-13139, isolated from corn steep liquor, produces
      two bactericidal peptides with respective estimated molecular masses of 4.5 and
      6.0 kDa upon denaturing sodium dodecyl sulfatepolyacrylamide gel electrophoresis.
      The antimicrobial activity detected in the fermentation supernatant fraction of
      L. amylovorus LMG P-13139 was heat stable (20 min, 121 degrees C), displayed a
      narrow inhibitory spectrum, and was sensitive to proteinase K, trypsin, and alpha
      chymotrypsin but insensitive to alpha-amylase, lysozyme, catalase, and lipase.
      The 4.5-kDa bacteriocin was purified and characterized and designated lactobin A.
      Lactobin A was isolated as a floating pellicle from culture supernatant brought
      to 35% saturation with ammonium sulfate. Upon this ammonium sulfate treatment,
      crude lactobin A was incorporated, together with Tween 80 as a major contaminant,
      in high-molecular-mass complexes sized at approximately 670 kDa by gel filtration
      chromatography. Contaminating fatty acids were removed from these micelles by a
      simple one-step methanol-chloroform extraction without loss of activity. Both
      inhibitory peptides were separated in an isocratic isopropanol gradient on a
      PepRPC 5/5 reversed-phase column, and both peptides retained activity towards
      Lactobacillus helveticus ATCC 15009 upon separation. Lactobin A has a molecular
      mass determined by electrospray mass spectrometry of 4,879 +/- 0.69 Da. Its
      peptide chain contains 50 unmodified amino acids, of which 26% are glycine
      residues and 40% are hydrophobic residues (A, V, L, I, and P). It displays the
      highest structural homology (42% identity and 28% similarity) with the lafX gene
      product, encoded by the second open reading frame of the lactacin F operon. These
      data strongly indicate that lactobin A belongs to the class IIb bacteriocins
      according to the classification of Klaenhammer.

PMID- 8979335
TI  - Experimental Escherichia coli O157:H7 carriage in calves.
AB  - Nine weaned calves (6 to 8 weeks of age) were given 10(10) CFU of a five-strain
      mixture of enterohemorrhagic Escherichia coli O157:H7 by oral-gastric intubation.
      After an initial brief period of pyrexia in three calves and transient mild
      diarrhea in five calves, calves were clinically normal throughout the 13- to 27
      day study. The population of E. coli O157:H7 in the faces decreased dramatically
      in all calves during the first 2 weeks after inoculation. Thereafter, small
      populations of E. coli O157:H7 persisted in all calves, where they were detected
      intermittently in the feces and rumen contents. While withholding food increased
      fecal shedding of E. coli O157:H7 by 1 to 2 log10/g in three of four calves
      previously shedding small populations of E. coli O157:H7, the effect of fasting
      on fecal shedding of E. coli O157:H7 was variable in calves shedding larger
      populations. At necropsy, E. coli O157:H7 was not isolated from sites outside the
      alimentary tract. E. coli O157:H7 was isolated from the forestomach or colon of
      all calves at necropsy. Greater numbers of E. coli O157:H7 were present in the
      gastrointestinal contents than in the corresponding mucosal sections, and there
      was no histologic or immunohistochemical evidence of E. coli O157:H7 adhering to
      the mucosa. In conclusion, under these experimental conditions, E. coli O157:H7
      is not pathogenic in weaned calves, and while it does not appear to colonize
      mucosal surfaces for extended periods, E. coli O157:H7 persists in the contents
      of the rumen and colon as a source for fecal shedding.

PMID- 8979336
TI  - Enhanced production of arginine and urea by genetically engineered Escherichia
      coli K-12 strains.
AB  - Escherichia coli strains capable of enhanced synthesis of arginine and urea were
      produced by derepression of the arginine regulon and simultaneous overexpression
      of the E. coli carAB and argI genes and the Bacillus subtilis rocF gene. Plasmids
      expressing carAB driven by their natural promoters were unstable. Therefore, E.
      coli carAB and argI genes with and without the B. subtilis rocF gene were
      constructed as a single operon under the regulation of the inducible promoter
      ptrc. Arginine operator sequences (Arg boxes) from argI were also cloned into the
      same plasmids for titration of the arginine repressor. Upon overexpression of
      these genes in E. coli strains, very high carbamyl phosphate synthetase,
      ornithine transcarbamylase, and arginase catalytic activities were achieved. The
      biosynthetic capacity of these engineered bacteria when overexpressing the
      arginine biosynthetic enzymes was 6- to 16-fold higher than that of controls but
      only if exogenous ornithine was present (ornithine was rate limiting).
      Overexpression of arginase in bacteria with a derepressed arginine biosynthetic
      pathway resulted in a 13- to 20-fold increase in urea production over that of
      controls with the parent vector alone; in this situation, the availability of
      carbamyl phosphate was rate limiting.

PMID- 8979337
TI  - Antimycoplasma properties and application in cell culture of surfactin, a
      lipopeptide antibiotic from Bacillus subtilis.
AB  - Surfactin, a cyclic lipopeptide antibiotic and biosurfactant produced by Bacillus
      subtilis, is well-known for its interactions with artificial and biomembrane
      systems (e.g., bacterial protoplasts or enveloped viruses). To assess the
      applicability of this antiviral and antibacterial drug, we determined the
      cytotoxicity of surfactin with a 50% cytotoxic concentration of 30 to 64 microM
      for a variety of human and animal cell lines in vitro. Concomitantly, we observed
      an improvement in proliferation rates and changes in the morphology of mycoplasma
      contaminated mammalian cells after treatment with this drug. A single treatment
      over one passage led to complete removal of viable Mycoplasma hyorhinis cells
      from various adherent cell lines, and Mycoplasma orale was removed from
      nonadherent human T-lymphoid cell lines by double treatment. This effect was
      monitored by a DNA fluorescence test, an enzyme-linked immunosorbent assay, and
      two different PCR methods. Disintegration of the mycoplasma membranes as observed
      by electron microscopy indicated the mode of action of surfactin. Disintegration
      is obviously due to a physicochemical interaction of the membrane-active
      surfactant with the outer part of the lipid membrane bilayer, which causes
      permeability changes and at higher concentrations leads finally to disintegration
      of the mycoplasma membrane system by a detergent effect. The low cytotoxicity of
      surfactin for mammalian cells permits specific inactivation of mycoplasmas
      without significant deleterious effects on cell metabolism and the proliferation
      rate in cell culture. These results were used to develop a fast and simple method
      for complete and permanent inactivation of mycoplasmas in mammalian monolayer and
      suspension cell cultures.

PMID- 8979338
TI  - Vertical distribution and phylogenetic characterization of marine planktonic
      Archaea in the Santa Barbara Channel.
AB  - Newly described phylogenetic lineages within the domain Archaea have recently
      been found to be significant components of marine picoplankton assemblages. To
      better understand the ecology of these microorganisms, we investigated the
      relative abundance, distribution, and phylogenetic composition of Archaea in the
      Santa Barbara Channel. Significant amounts of archaeal rRNA and rDNA (genes
      coding for rRNA) were detected in all samples analyzed. The relative abundance of
      archaeal rRNA as measured by quantitative oligonucleotide hybridization
      experiments was low in surface waters but reached higher values (20 to 30% of
      prokaryotic rRNA) at depths below 100 m. Probes were developed for the two major
      groups of marine Archaea detected. rRNA originating from the euryarchaeal group
      (group II) was most abundant in surface waters, whereas rRNA from the
      crenarchaeal group (group I) dominated at depth. Clone libraries of PCR-amplified
      archaeal rRNA genes were constructed with samples from 0 and 200 m deep.
      Screening of libraries by hybridization with specific oligonucleotide probes, as
      well as subsequent sequencing of the cloned genes, indicated that virtually all
      archaeal rDNA clones recovered belonged to one of the two groups. The recovery of
      cloned rDNA sequence types in depth profiles exhibited the same trends as were
      observed in quantitative rRNA hybridization experiments. One representative of
      each of 18 distinct restriction fragment length polymorphism types was partially
      sequenced. Recovered sequences spanned most of the previously reported
      phylogenetic diversity detected in planktonic crenarchaeal and euryarchaeal
      groups. Several rDNA sequences appeared to be harbored in archaeal types which
      are widely distributed in marine coastal waters. In total, data suggest that
      marine planktonic crenarchaea and euryarchaea of temperate coastal habitats
      thrive in different zones of the water column. The relative rRNA abundance of the
      crenarchaeal group suggests that its members constitute a significant fraction of
      the prokaryotic biomass in subsurface coastal waters.

PMID- 8979339
TI  - The Agaricus bisporus pruA gene encodes a cytosolic delta 1-pyrroline-5
      carboxylate dehydrogenase which is expressed in fruit bodies but not in gill
      tissue.
AB  - A fortuitously cloned 3'-truncated cDNA encoding the Agaricus bisporus delta 1
      pyrroline-5-carboxylate dehydrogenase was used to characterize the complete gene.
      The gene would encode a cytosolic polypeptide of 546 amino acids, and the
      basidiomycetous gene was evenly expressed in various parts of the mushroom except
      for the gills. No expression was detected in compost-grown mycelium. The steady
      state mRNA level of the gene in the vegetative phase was determined on simple
      synthetic media and was two- to threefold higher with ammonium or proline as the
      sole nitrogen source compared to glutamate as the sole nitrogen source. Moreover,
      the steady-state mRNA level was not markedly influenced by addition of ammonium
      phosphate to proline- or glutamate-utilizing cultures. The results suggest that
      ammonium and the amino acids proline and glutamate are equally preferred nitrogen
      sources in this organism and are consistent with previous observations of H. M
      Kalisz, D.A. Wood, and D. Moore (Trans. Br. Mycol. Soc. 88:221-227, 1987) that A.
      bisporus continues to degrade protein and secrete ammonium even if ammonium and
      glucose are present in the culture medium.

PMID- 8979340
TI  - Diversity and depth-specific distribution of SAR11 cluster rRNA genes from marine
      planktonic bacteria.
AB  - Small-subunit (SSU) ribosomal DNA (rDNA) gene clusters are phylogenetically
      related sets of SSU rRNA genes, commonly encountered in genes amplified from
      natural populations. Genetic variability in gene clusters could result from
      artifacts (polymerase error or PCR chimera formation), microevolution (variation
      among rrn copies within strains), or macroevolution (genetic divergence
      correlated with long-term evolutionary divergence). To better understand gene
      clusters this study assessed genetic diversity and distribution of a single
      environmental SSU rDNA gene cluster, the SAR11 cluster. SAR11 cluster genes, from
      an uncultured group of the alpha subclass of the class Proteobacteria, have been
      recovered from coastal and midoceanic waters of the North Atlantic and Pacific.
      We cloned and bidirectionally sequenced 23 new SAR11 cluster 16S rRNA genes, from
      80 and 250 m in the Sargasso Sea and from surface coastal waters of the Atlantic
      and Pacific, and analyzed them with previously published sequences. Two SAR11
      genes were obviously PCR chimeras, but the biological (nonchimeric) origins of
      most subgroups within the cluster were confirmed by independent recovery from
      separate gene libraries. Using group-specific oligonucleotide probes, we analyzed
      depth profiles of nucleic acids, targeting both amplified rDNAs and bulk RNAs.
      Two subgroups within the SAR11 cluster showed different highly depth-specific
      distributions. We conclude that some of the genetic diversity within the SAR11
      gene cluster represents macroevolutionary divergence correlated with niche
      specialization. Furthermore, we demonstrate the utility for marine microbial
      ecology of oligonucleotide probes based on gene sequences amplified from natural
      populations and show that a detailed knowledge of sequence variability may be
      needed to effectively design these probes.

PMID- 8979342
TI  - Phylogenetic diversity of bacterial symbionts of Solemya hosts based on
      comparative sequence analysis of 16S rRNA genes.
AB  - The bacterial endosymbionts of two species of the bivalve genus Solemya from the
      Pacific Ocean, Solemya terraeregina and Solemya pusilla, were characterized.
      Prokaryotic cells resembling gram-negative bacteria were observed in the gills of
      both host species by transmission electron microscopy. The ultrastructure of the
      symbiosis in both host species is remarkably similar to that of all previously
      described Solemya spp. By using sequence data from 16S rRNA, the identity and
      evolutionary origins of the S. terraeregina and S. pusilla symbionts were also
      determined. Direct sequencing of PCR-amplified products from host gill DNA with
      primers specific for Bacteria 16S rRNA genes gave a single, unambiguous sequence
      for each of the two symbiont species. In situ hybridization with symbiont
      specific oligonucleotide probes confirmed that these gene sequences belong to the
      bacteria residing in the hosts gills. Phylogenetic analyses of the 16S rRNA gene
      sequences by both distance and parsimony methods identify the S. terraeregina and
      S. pusilla symbionts as members of the gamma subdivision of the Proteobacteria.
      In contrast to symbionts of other bivalve families, which appear to be
      monophyletic, the S. terraeregina and S. pusilla symbionts share a more recent
      common ancestry with bacteria associating endosymbiotically with bivalves of the
      superfamily Lucinacea than with other Solemya symbionts (host species S. velum,
      S. occidentalis, and S. reidi). Overall, the 16S rRNA gene sequence data suggest
      that the symbionts of Solemya hosts represent at least two distinct bacterial
      lineages within the gamma-Proteobacteria. While it is increasingly clear that all
      extant species of Solemya live in symbiosis with specific bacteria, the
      associations appear to have multiple evolutionary origins.

PMID- 8979341
TI  - Identification and characterization of a Pantoea citrea gene encoding glucose
      dehydrogenase that is essential for causing pink disease of pineapple.
AB  - Pantoea citrea, a member of the family Enterobacteriaceae, causes pink disease of
      pineapple, whose symptom is characterized by the formation of pink to brown
      discolorations of the infected portions of the pineapple fruit cylinder upon
      canning. Molecular genetic approaches were applied to elucidate the mechanism
      responsible for this fruit discoloration. A P. citrea mutant strain, CMC6,
      defective in its ability to cause pink disease and fruit discoloration, was
      generated by nitrosoguanidine mutagenesis. A DNA fragment that restored these
      activities was isolated by screening a genomic cosmid library of P. citrea. A
      large open reading frame of 2,361 bp, identified by nucleotide sequencing of a
      subclone of the complementing DNA, showed high similarities to identified genes
      encoding glucose dehydrogenase (GDH) in Escherichia coli, Acinetobacter
      calcoaceticus, and Gluconobacter oxydans. The predicted amino acid sequence of
      GDH of P. citrea was identical to known GDHs in these bacteria by 54, 44, and
      34%, respectively. GDH of P. citrea has a predicted molecular mass of 86.2 kDa,
      contains a conserved binding domain for the cofactor pyrroloquinoline quinone,
      and possesses GDH activity as demonstrated by biochemical assay. GDH is the key
      branch point enzyme leading to the biosynthesis of gluconate, which in turn
      serves as the substrate leading to the formation of 2-ketogluconate, 2,5
      diketogluconate, 6-phosphogluconate, and 2-keto-6-phosphogluconate. Addition of
      gluconate to CMC6 restores the juice- and fruit-discoloring activity. Although
      the pigments formed by heating (or canning) have not been identified, it is clear
      that GDH is one of the enzymes required for pigment formation leading to pink
      disease.

PMID- 8979343
TI  - Availability of iron to Pseudomonas fluorescens in rhizosphere and bulk soil
      evaluated with an ice nucleation reporter gene.
AB  - The biological availability of iron in the rhizosphere was assessed by evaluating
      ice nucleation activity (INA) expressed in situ by Pseudomonas fluorescens Pf-5
      containing a transcriptional fusion (pvd-inaZ) of an iron-regulated promoter to
      an ice nucleation reporter gene (inaZ). Pf-5 containing pvd-inaZ expresses INA
      that is inversely related to the iron availability of a growth medium (J. E.
      Loper and S. E. Lindow, Appl. Environ. Microbiol. 60:1934-1941, 1994). INA
      expressed by rhizosphere populations of Pf-5 containing pvd-inaZ was at a maximum
      within 12 to 24 h following inoculation of the bacterium onto bean roots and
      typically decreased gradually during the following 4 days. Iron availability in
      the soil, which was altered by the addition of chelators, influenced INA
      expressed by rhizosphere populations of Pf-5 containing pvd-inaZ. In soil
      adjusted to a pH of 7.0 or 8.0 by adding Ca(OH)2, rhizosphere populations of Pf-5
      containing pvd-inaZ expressed greater INA, indicating lower iron availability,
      than they did in the nonamended soil at a pH of 5.4. Similarly, rhizosphere
      populations of Pf-5 containing pvd-inaZ expressed less INA in an agricultural
      soil of pH 5.4 than in other agricultural soils ranging in pH from 6.4 to 7.7.
      These results conform to the predictions of chemical models stating that pH is a
      major factor influencing iron availability in soil solutions. The results of this
      study indicate that P. fluorescens Pf-5 encountered an iron-limited environment
      immediately after it was inoculated onto bean roots planted in agricultural field
      soils. One to two days after the bacterium was inoculated onto root surfaces,
      however, iron became more available to rhizosphere populations of Pf-5. We
      speculate that iron acquisition systems of plants and other rhizosphere organisms
      may provide available sources of iron to established rhizosphere populations of
      P. fluorescens.

PMID- 8979344
TI  - Comparison of primers and optimization of PCR conditions for detection of
      Cryptosporidium parvum and Giardia lamblia in water.
AB  - Eight pairs of published PCR primers were evaluated for the specific detection of
      Cryptosporidium parvum and Giardia lamblia in water. Detection sensitivities
      ranged from 1 to 10 oocysts or cysts for purified preparations and 5 to 50
      oocysts or cysts for seeded environmental water samples. Maximum sensitivity was
      achieved with two successive rounds of amplification and hybridization, with
      oligonucleotide probes detected by chemiluminescence. Primer annealing
      temperatures and MgCl2 concentrations were optimized, and the specificities of
      the primer pairs were determined with closely related species. Some of the
      primers were species specific, while others were only genus specific. Multiplex
      PCR for the simultaneous detection of Cryptosporidium and Giardia was
      demonstrated with primers amplifying 256- and 163-bp products from the 18S rRNA
      gene of Cryptosporidium and the heat shock protein gene of Giardia, respectively.
      The results demonstrate the potential utility of PCR for the detection of
      pathogenic protozoa in water but emphasize the necessity of continued
      development.

PMID- 8979345
TI  - Obligate intracellular bacterial parasites of acanthamoebae related to Chlamydia
      spp.
AB  - The phylogeny of obligate intracellular coccoid parasites of acanthamoebae
      isolated from the nasal mucosa of humans was analyzed by the rRNA approach. The
      primary structures of the 16S and 23S rRNA molecules of one strain were
      determined in almost full length. In situ hybridization with a horseradish
      peroxidase-labeled oligonucleotide probe targeted to a unique signature site
      undoubtedly correlated the retrieved 16S rRNA sequence to the respective
      intracellular parasite. This probe also hybridized with the second strain,
      suggesting a close relationship between the two intracellular parasites.
      Comparative sequence analysis demonstrated a distinct relationship to the genus
      Chlamydia. With 16S rRNA similarities of 86 to 87% to the hitherto-sequenced
      Chlamydia species, the intracellular parasites are likely not new species of this
      genus but representatives of another genus in the family of the Chlamydiaceae.
      Consequently, it is proposed to provisionally classify the endoparasite of
      Acanthamoeba sp. strain Bn9 as "Candidatus Parachlamydia acanthamoebae." From an
      epidemiological perspective, the results suggest that small amoebae could be
      environmental reservoirs and vectors for a variety of potentially pathogenic
      bacteria including members of the Chlamydiaceae.

PMID- 8979346
TI  - Stable expression of pertussis toxin in Bordetella bronchiseptica under the
      control of a tightly regulated promoter.
AB  - Pertussis toxin (PT) is an essential component of accellular vaccines against
      whooping cough. However, the industrial production of PT from Bordetella
      pertussis is impaired by slow growth and poor yields. To overcome these problems,
      we have constructed a minitransposon containing the tox operon under the control
      of a tightly regulated promoter responsive to an aromatic inducer. The expression
      cassettes have been integrated into the chromosome of Bordetella bronchiseptica
      5376 and ATCC 10580 bvg. Five recombinant clones containing the tox operon under
      the control of the Psal promoter, which is activated by the product of nahR, were
      further characterized. The recombinant clones expressed PT after only 3 h of
      induction with sodium salicylate at levels similar to those of B. pertussis grown
      for 24 h. The stability of the engineered phenotype was 100% after 72 h of growth
      without selective pressure. The growth pattern was not modified either under
      noninducing conditions or in the presence of the inducer at low concentrations,
      suggesting that strain performance would not be affected in bioreactors when
      uncoupled from gene expression. Recombinant PT, which was localized mainly in the
      periplasm, was purified by affinity chromatography. The recombinant protein was
      immunologically indistinguishable from wild-type PT and retained its biological
      activity as determined by the CHO cell-clustering test. These recombinant clones
      appear to be useful tools for the cost-effective production of PT under
      conditions of improved biosafety, as demonstrated by the inducible expression of
      PT uncoupled from the bacterial biomass in a nonvirulent and fast-growing B.
      bronchiseptica background.

PMID- 8979347
TI  - Physiological response to anaerobicity of glycerol-3-phosphate dehydrogenase
      mutants of Saccharomyces cerevisiae.
AB  - Mutants of Saccharomyces cerevisiae, in which one or both of the genes encoding
      the two isoforms of NAD-dependent glycerol-3-phosphate dehydrogenase had been
      deleted, were studied in aerobic batch cultures and in aerobic-anaerobic step
      change experiments. The respirofermentative growth rates under aerobic conditions
      with semisynthetic medium (20 g of glucose per liter) of two single mutants, gpd1
      delta and gpd2 delta, and the parental strain (mu = 0.5 h-1) were almost
      identical, whereas the growth rate of a double mutant, gpd1 delta gpd2 delta, was
      approximately half that of the parental strain. Upon a step change from aerobic
      to anaerobic conditions in the exponential growth phase, the specific carbon
      dioxide evolution rates (CER) of the wild-type strain and the gpd1 delta strain
      were almost unchanged. The gpd2 delta mutant showed an immediate, large (> 50%)
      decrease in CER upon a change to anaerobic conditions. However, after about 45
      min the CER increased again, although not to the same level as under aerobic
      conditions. The gpd1 delta gpd2 delta mutant showed a drastic fermentation rate
      decrease upon a transition to anaerobic conditions. However, the CER values
      increased to and even exceeded the aerobic levels after the addition of acetoin.
      High-pressure liquid chromatographic analyses demonstrated that the added acetoin
      served as an acceptor of reducing equivalents by being reduced to butanediol. The
      results clearly show the necessity of glycerol formation as a redox sink for S.
      cerevisiae under anaerobic conditions.

PMID- 8979348
TI  - Influence of invertase activity and glycerol synthesis and retention on
      fermentation of media with a high sugar concentration by Saccharomyces
      cerevisiae.
AB  - In the past, the fermentation activity of Saccharomyces cerevisiae in substrates
      with a high concentration of sucrose (HSuc), such as sweet bread doughs, has been
      linked inversely to invertase activity of yeast strains. The present work defines
      the limits of the relationship between invertase activity and fermentation in
      hyperosmotic HSuc medium. Fourteen polyploid, wild-type strains of S. cerevisiae
      with different invertase levels gave a similar ranking of fermentation activity
      in HSuc and in medium in which glucose and fructose replaced sucrose (HGF
      medium). Thus, invertase is unlikely to be the most important determinant of
      fermentation in sweet doughs. Yeasts produce the compatible solute-osmoprotective
      compound glycerol when exposed to hyperosmotic environments. Under low sugar
      concentrations (and nonstressing osmotic pressure), there was no correlation
      between glycerol and fermentation activities. However, there was a strong
      correlation between the ability of yeasts to ferment in HSuc or HGF medium and
      their capacity to produce and retain glycerol intracellularly. There was also a
      strong correlation between intracellular glycerol and fermentation activity of
      yeasts in a medium in which the nonfermentable sugar alcohol sorbitol replaced
      most of the sugars (HSor), but the ability to produce and retain glycerol was
      greater when yeasts were incubated in HGF medium under the same osmotic pressure.
      The difference between the amounts of glycerol produced and retained in HSor and
      in HGF media varied with strains. This implies that high fermentable sugar
      concentrations cause physiological conditions that allow for enhanced glycerol
      production and retention, the degree of which is strain dependent. In conclusion,
      one important prerequisite for yeast strains to ferment media with high
      concentrations of sugar is the ability to synthesize glycerol and especially to
      retain it.

PMID- 8979350
TI  - Purification and characterization of extremely thermostable beta-mannanase, beta
      mannosidase, and alpha-galactosidase from the hyperthermophilic eubacterium
      Thermotoga neapolitana 5068.
AB  - Thermostable and thermoactive beta-mannanase (1,4-beta-D-mannan mannanohydrolase
      [EC 3.2.1.78]), beta-mannosidase (beta-D-mannopyranoside hydrolase [EC 3.2.1.25])
      and alpha-galactosidase (alpha-D-galactoside galactohydrolase [EC 3.2.1.22]) were
      purified to homogeneity from cell extracts and extracellular culture supernatants
      of the hyperthermophilic eubacterium Thermotoga neapolitana 5068 grown on guar
      gum-based media. The beta-mannanase was an extracellular monomeric enzyme with a
      molecular mass of 65 kDa. The optimal temperature for activity was 90 to 92
      degrees C, with half-lives (t1/2) of 34 h at 85 degrees C, 13 h at 90 degrees C,
      and 35 min at 100 degrees C. The beta-mannosidase and alpha-galactosidase were
      found primarily in cell extracts. The beta-mannosidase was a homodimer consisting
      of approximately 100-kDa molecular mass subunits. The optimal temperature for
      activity was 87 degrees C, with t1/2 of 18 h at 85 degrees C, 42 min at 90
      degrees C, and 2 min at 98 degrees C. The alpha-galactosidase was a 61-kDa
      monomeric enzyme with a temperature optimum of 100 to 103 degrees C and t1/2 of 9
      h at 85 degrees C, 2 h at 90 degrees C, and 3 min at 100 degrees C. These enzymes
      represent the most thermostable and thermoactive versions of these types yet
      reported and probably act synergistically to hydrolyze extracellular
      galactomannans to monosaccharides by T. neapolitana for nutritional purposes. The
      significance of such substrates in geothermal environments remains to be seen.

PMID- 8979351
TI  - Effect of 2-bromoethanesulfonic acid and Peptostreptococcus productus ATCC 35244
      addition on stimulation of reductive acetogenesis in the ruminal ecosystem by
      selective inhibition of methanogenesis.
AB  - Evidence is provided that reductive acetogenesis can be stimulated in ruminal
      samples during short-term (24-h) incubations when methanogenesis is inhibited
      selectively. While addition of the reductive acetogen Peptostreptococcus
      productus ATCC 35244 alone had no significant influence on CH4 and volatile fatty
      acid (VFA) production in ruminal samples, the addition of this strain together
      with 2-bromoethanesulfonic acid (BES) (final concentration, 0.01 or 0.03 mM)
      resulted in stimulation of acetic acid production and H2 consumption. Since
      acetate production exceeded amounts that could be attributed to reductive
      acetogenesis, as measured by H2 consumption, it was found that P. productus also
      fermented C6 units (glucose and fructose) heterotrophically to mainly acetate (>
      99% of the total VFA). Using 14CH3COOH, we concluded that addition of BES and BES
      plus P. productus did not alter the consumption of acetate in ruminal samples.
      The addition of P. productus to BES-treated ruminal samples caused supplemental
      inhibition of CH4 production and stimulation of VFA production, representing a
      possible energy gain of about 13 to 15%.

PMID- 8979352
TI  - An Aspergillus niger esterase (ferulic acid esterase III) and a recombinant
      Pseudomonas fluorescens subsp. cellulosa esterase (Xy1D) release a 5-5' ferulic
      dehydrodimer (diferulic acid) from barley and wheat cell walls.
AB  - Diferulate esters strengthen and cross-link primary plant cell walls and help to
      defend the plant from invading microbes. Phenolics also limit the degradation of
      plant cell walls by saprophytic microbes and by anaerobic microorganisms in the
      rumen. We show that incubation of wheat and barley cell walls with ferulic acid
      esterase from Aspergillus niger (FAE-III) or Pseudomonas fluorescens (Xy1D),
      together with either xylanase I from Aspergillus niger, Trichoderma viride
      xylanase, or xylanase from Pseudomonas fluorescens (XylA), leads to release of
      the ferulate dimer 5-5' diFA [(E,E)-4,4'-dihydroxy-5,5'-dimethoxy-3,3'-bicinnamic
      acid]. Direct saponification of the cell walls without enzyme treatment released
      the following five identifiable ferulate dimers (in order of abundance): (Z)-beta
      (4-[(E)-2-carboxyvinyl]-2-methoxyphenoxy)-4-hydroxy-3-methoxycinnamic acid, trans
      5-[(E)-2-carboxyvinyl]-2-(4-hydroxy-3-methoxy-phenyl) -7-methoxy-2, 3
      dihydrobenzofuran-3-carboxylic acid, 5-5' diFA, (E,E)-4, 4'-dihydroxy-3, 5'
      dimethoxy-beta, 3'-bicinnamic acid, and trans-7-hydroxy-1-(4-hydroxy-3
      methoxyphenyl) -6-methoxy-1, 2-dihydronaphthalene-2, 3-dicarboxylic acid.
      Incubation of the wheat or barley cell walls with xylanase, followed by
      saponification of the solubilized fraction, yielded 5-5'diFA and, in some cases,
      certain of the above dimers, depending on the xylanase used. These experiments
      demonstrate that FAE-III and XYLD specifically release only esters of 5-5'diFA
      from either xylanase-treated or insoluble fractions of cell walls, even though
      other esterified dimers were solubilized by preincubation with xylanase. It is
      also concluded that the esterified dimer content of the xylanase-solubilized
      fraction depends on the source of the xylanase.

PMID- 8979353
TI  - Isolation and molecular identification of planctomycete bacteria from postlarvae
      of the giant tiger prawn, Penaeus monodon.
AB  - Bacteria phenotypically resembling members of the phylogenetically distinct
      planctomycete group of the domain Bacteria were isolated from postlarvae of the
      giant tiger prawn, Penaeus monodon. A selective medium designed in the light of
      planctomycete antibiotic resistance characteristics was used for this isolation.
      Planctomycetes were isolated from both healthy and monodon baculovirus-infected
      prawn postlarvae. The predominant colony type recovered from postlarvae
      regardless of viral infection status was nonpigmented. Other, less commonly
      observed types were pink or orange pigmented. A planctomycete-specific 16S rRNA
      directed probe was designed and used to screen the isolates for their identity as
      planctomycetes prior to molecular phylogenetic characterization. 16S rRNA genes
      from nine prawn isolates together with two planctomycete reference strains
      (Planctomyces brasiliensis and Gemmata obscuriglobus) were sequenced and compared
      with reference sequences from the planctomycetes and other members of the domain
      Bacteria. Phylogenetic analyses and sequence signatures of the 16S rRNA genes
      demonstrated that the prawn isolates were members of the planctomycete group.
      Five representatives of the predominant nonpigmented colony type were members of
      the Pirellula group within the planctomycetes, as were three pink-pigmented
      colony type representatives. Homology values and tree topology indicated that
      representatives of the nonpigmented and pink-pigmented colony types formed two
      discrete clusters within the Pirellula group, not identical to any known
      Pirellula species. A sole representative of the orange colony type was a member
      of the Planctomyces group, virtually identical in 16S rDNA sequence to P.
      brasiliensis, and exhibited distinctive morphology.

PMID- 8979354
TI  - Molecular cloning, expression, and characterization of a functional single-chain
      Fv antibody to the mycotoxin zearalenone.
AB  - The heavy-chain and kappa light-chain variable region genes of an antizearalenone
      hybridoma cell line (2G3-6E3-2E2) were isolated by PCR and joined by a DNA linker
      encoding peptide (Gly4Ser)3 as a single-chain Fv (scFv) DNA fragment. The scFv
      DNA fragment was cloned into a phagemid (pCANTAB5E) and expressed as a fusion
      protein with E tag and phage M13 p3 in Escherichia coli TG1. In the presence of
      helper phage M13K07, the scFv fusion protein was displayed on the surfaces of
      recombinant phages. High-affinity scFv phages were enriched through affinity
      selection in microtiter wells coated with zearalenone-ovalbumin conjugate. The
      selected recombinant phages were used to infect E. coli HB2151 for the production
      of soluble scFv antibodies. One selected clone (pQY1.5) in HB2151 secreted a
      soluble scFv antibody (QY1.5) with a high zearalenone-binding affinity
      (concentration required for 50% inhibition of binding, 14 ng/ml), similar to that
      of parent monoclonal antibody in a competitive indirect enzyme-linked
      immunosorbent assay. However, scFv QY1.5 exhibited higher cross-reactivity with
      zearalenone analogs and had greater sensitivity to methanol destabilization than
      the parent monoclonal antibody did. Nucleotide sequence analyses revealed that
      the light-chain portion of scFv QY1.5 had a nucleotide sequence identity of 97%
      to a mouse germ line gene VK23.32 in mouse kappa light-chain variable region
      subgroup V, whereas the heavy-chain nucleotide sequence was classified as mouse
      heavy-chain subgroup III (D) but without any closely related members having
      highly homologous complementarity-determining region sequences. The potential of
      soluble scFv QY1.5 for routine screening of zearalenone and its analogs was
      demonstrated with zearalenone-spiked corn extracts.

PMID- 8979355
TI  - Succession and convergence of biofilm communities in fixed-film reactors treating
      aromatic hydrocarbons in groundwater.
AB  - Community composition, succession, and performance were compared in three
      fluidized bed reactors (FBR) operated to test preemptive colonization and the
      influence of toluene compared with a mixture of benzene, toluene, and p-xylene
      (BTX) as feeds. One reactor was inoculated with toluene-degrading strains
      Pseudomonas putida PaW1, Burkholderia cepacia G4, and B. pickettii PKO1. PaW1
      outcompeted the other two strains. When groundwater strains were allowed to
      challenge the steady-state biofilm developed by inoculated strains, they readily
      displaced the inoculated strains and further reduced the toluene effluent
      concentration from 0.140 to 0.063 mg/liter for 98% removal. Amplified ribosomal
      DNA restriction analysis (ARDRA) of reactor community DNA showed a succession of
      populations to a pattern that was stable for at least 4 months of operation.
      Parallel reactors fed toluene and BTX but inoculated directly from groundwater
      had the same treatment performance and the same ARDRA profiles as each other and
      as the seeded reactor once the groundwater community took over. Convergence and
      stability of populations were confirmed by genotype analysis of 120 isolates
      taken from all reactors and at several times. Ninety percent of the isolates were
      of 4 of the 12 genotypes found, and their ARDRA patterns accounted for most of
      the community ARDRA patterns. Estimates of the maximum specific growth rates (mu
      max), half-saturation constants (K(m)), and maximum substrate utilization rates
      (Vmax) of the 12 genotypes isolated revealed a rather high diversity of toluene
      use kinetics even though the toluene in the feed was constant. The climax
      populations, however, generally showed kinetic parameters indicative of greater
      competitiveness than the inocula. rRNA sequence analysis of three codominant
      strains showed them to be members of the alpha, beta, and gamma subdivisions of
      the Proteobacteria. Two were similar to Comamonas and Pseudomonas putida, but the
      member of the alpha group was somewhat distant from any organism in the rRNA
      database. The convergence of communities to the same composition from three
      different starting conditions and their constancy over several months suggests
      that a rather stable community was selected.

PMID- 8979357
TI  - A nucleic acid sequence-based amplification system for detection of Listeria
      monocytogenes hlyA sequences.
AB  - A nucleic acid sequence-based amplification system primarily targeting mRNA from
      the Listeria monocytogenes hlyA gene was developed. This system enabled the
      detection of low numbers (< 10 CFU/g) of L. monocytogenes cells inoculated into a
      variety of dairy and egg products after 48 h of enrichment in modified listeria
      enrichment broth.

PMID- 8979356
TI  - Comparative analysis of Pseudomonas syringae pv. actinidiae and pv. phaseolicola
      based on phaseolotoxin-resistant ornithine carbamoyltransferase gene (argK) and
      16S-23S rRNA intergenic spacer sequences.
AB  - Pseudomonas syringae pv. phaseolicola, which causes halo blight on various
      legumes, and pv. actinidiae, responsible for canker or leaf spot on actinidia
      plants, are known as phaseolotoxin producers, and the former possesses
      phaseolotoxin-resistant ornithine carbamoyltransferase (ROCT) which confers
      resistance to the toxin. We confirmed that the latter is also resistant to
      phaseolotoxin and possesses ROCT, and we compared the two pathovars by using
      sequence data of the ROCT gene and the intergenic spacer region located between
      the 16S and 23S rRNA genes (16S-23S spacer region) as an index. It was found that
      the identical ROCT gene (argK) is contained not only in bean isolates of P.
      syringae pv. phaseolicola in Mexico and the United States but also in bean
      isolates in Japan and Canada, and that it is also distributed in the kudzu
      (Pueraria lobata) isolates of P. syringae pv. phaseolicola. Moreover, the
      kiwifruit and tara vine isolates of P. syringae pv. actinidiae were also found to
      possess the identical argK. On the contrary, the 16S-23S spacer regions showed a
      significant level of sequence variation between P. syringae pv. actinidiae and
      pv. phaseolicola, suggesting that these two pathovars evolved differently from
      each other in the phylogenetic development. The fact that even synonymous
      substitution has not occurred in argK among these strains despite their extreme
      differences in phylogenetic evolution and geographical distribution suggests that
      it was only recently in evolutionary time that argK was transferred from its
      origin to P. syringae pv. actinidiae and/or pv. phaseolicola.

PMID- 8979358
TI  - Purification and characterization of a prolidase from Lactobacillus casei subsp.
      casei IFPL 731.
AB  - A peptidase showing a high level of specificity towards dipeptides of the X-Pro
      type was purified to homogeneity from the cell extract of Lactobacillus casei
      subsp. casei IFPL 731. The enzyme was a monomer having a molecular mass of 41
      kDa. The pH and temperature optima were 6.5 to 7.5 and 55 degrees C,
      respectively. Metal chelating agents completely inhibited enzyme activity,
      indicating that the prolidase was a metalloenzyme. The Michaelis constant (K(m))
      and Vmax for several proline-containing dipeptides were determined.

PMID- 8979359
TI  - Recovery of crenarchaeotal ribosomal DNA sequences from freshwater-lake
      sediments.
AB  - We report several novel environmental sequences of archaea from the kingdom
      Crenarchaeota, recovered from anaerobic freshwater-lake sediments in Michigan. A
      nested PCR approach with Archaea- and Crenar-chaeota-specific primers was used to
      amplify partial Small-subunit ribosomal DNAs. Phylogenetic analysis of seven
      sequences shows that these DNAs represent a monophyletic lineage diverging prior
      to all recently identified crenarchaeotal phylotypes isolated from temperate
      environments. Including our lineage, all uncultured crenarchaeotal sequences
      recovered from moderate or cold environments form a distinct, monophyletic group
      separate from the "genuine" thermophilic crenarchaeota. Our finding extends the
      emerging picture that crenarchaeota, thought until recently to be solely extreme
      thermophiles, have radiated into an unexpectedly large variety of ecologically
      important, temperate environments.

PMID- 8979360
TI  - Detection of viable Giardia cysts by amplification of heat shock-induced mRNA.
AB  - Primers obtained from gene sequences coding for heat shock proteins (HSP) were
      used to specifically detect enteric protozoans of the genus Giardia. The HSP
      primers amplified Giardia DNA or the corresponding RNA sequences obtained from
      lysed cysts and gave a 163-bp product. Since the presence of the product did not
      indicate whether the cysts were viable, these amplifications are a
      presence/absence test only. In contrast, amplification of heat shock-induced mRNA
      utilizing the same HSP primers was indicative of viable Giardia cysts. The limit
      of sensitivity of the presence/absence test was 1 cyst, whereas for the viability
      test it was 10 cysts. Thus, viable Giardia cysts can be rapidly and specifically
      detected with great sensitivity through the use of PCR amplifications.

PMID- 8979361
TI  - Nylon biodegradation by lignin-degrading fungi.
AB  - The biodegradation of nylon by lignin-degrading fungi was investigated. The
      fungus IZU-154 significantly degraded nylon-66 membrane under ligninolytic
      conditions. Nuclear magnetic resonance analysis showed that four end groups, CHO,
      NHCHO, CH3, and CONH2, were formed in the biodegraded nylon-66 membranes,
      suggesting that nylon-66 was degraded oxidatively.

PMID- 8979362
TI  - Development of a species-specific gene probe for Hyphomicrobium facilis with the
      inverse PCR.
AB  - A species-specific gene probe for Hyphomicrobium facilis was generated from a
      transposon Tn5-132 insertion mutant defective in methanol oxidation by the
      inverse PCR. With this probe, the abundance of H. facilis in a garden soil was
      determined as a subfraction of the total cultivable hyphomicrobia.

PMID- 8979365
TI  - Leucocyte binding to the uterine epithelial cell surface during lectin-induced
      decidualization.
AB  - Intra-uterine injection of the lectin Concanavalin A (ConA) on day 5 of
      pseudopregnancy induced a rapid and persistent infiltration of leucocytes into
      the rat uterine stroma. Although the infiltration of leucocytes was seen along
      the entire length of the uterine horn, areas of stromal oedema, indicative of
      decidualization (as indicated by a positive Pontamine Sky Blue reaction), were
      only associated with regions in which leucocytes had crossed the uterine
      epithelium and were present in the uterine lumen. Ultrastructural evaluation of
      the interaction of the luminal leucocytes with the apical surface of the uterine
      epithelium appeared strikingly similar to that of the blastocyst and the uterine
      epithelium during normal implantation. It is proposed that leucocytes, induced by
      ConA, may initiate a decidual response in a manner analogous to that of the
      blastocyst through surface epithelial interaction.

PMID- 8979363
TI  - Characterization of the Agrobacterium vitis pehA gene and comparison of the
      encoded polygalacturonase with the homologous enzymes from Erwinia carotovora and
      Ralstonia solanacearum.
AB  - DNA sequencing of the Agrobacterium vitis pehA gene revealed a predicted protein
      with an M(r) of 58,000 and significant similarity to the polygalacturonases of
      two other plant pathogens, Erwinia carotovora and Ralstonia (= Pseudomonas or
      Burkholderia) solanacearum. Sequencing of the N terminus of the PehA protein
      demonstrated cleavage of a 34-amino-acid signal peptide from pre-PehA. Mature
      PehA accumulated primarily in the periplasm of A. vitis and pehA+ Escherichia
      coli cells during exponential growth. A. vitis PehA released dimers, trimers, and
      monomers from polygalacturonic acid and caused less electrolyte leakage from
      potato tuber tissue than did the E. carotovora and R. solanacearum
      polygalacturonases.

PMID- 8979366
TI  - The C-terminal Src kinase (Csk) is widely expressed, active in HT-29 cells that
      contain activated Src, and its expression is downregulated in butyrate-treated
      SW620 cells.
AB  - Csk expression was examined in human glioma, breast and colon cell lines, along
      with murine tissues. Relative to colon and glioma cell lines, Csk expression was
      highest in the breast cell lines. Relative to brain tissue, expression was 100
      fold higher in the heart, kidney, liver, lung and spleen. Subcellular
      fractionation and cellular immunostaining indicated that it was localized in the
      cytosolic fraction. The expression of Csk was downregulated upon chemical-induced
      differentiation of SW620 human colon cells by treatment with sodium butyrate. Its
      expression localization and activity relative to Src are discussed.

PMID- 8979368
TI  - Properties of nuclear matrix proteins that bind the 5' flanking region of the
      haptoglobin gene are changed during the acute-phase response.
AB  - It was previously shown that during the acute-phase response-induced elevated
      transcription of the rat haptoglobin gene, protein p55 and the lamins mediate the
      increased binding of restriction fragment II (-541/-146) via a 38 bp adenine
      tract lying 147 bp upstream from the haptoglobin gene cis element (-165/-56), to
      scaffold type II-like nuclear matrices. Here we show that the fragment II binding
      pattern to > or = 40 kDa proteins of nuclear matrices analogous to type I
      scaffolds is more complex. Fragment II bound conspicuously to a 40 and less so to
      p55, a 60 kDa protein and the lamins of control matrices. During increased gene
      transcription, it bound prominently to p55, the lamins, and less so to 45 and 52
      kDa proteins. This was accompanied by the tenacious binding of the DNA to
      isolated nuclear matrices in vitro and post-translational modifications of
      certain matrix proteins. The lamins and p55 demonstrated a greater N
      acetylglucosamine/sialic acid content and p55 an increased in vitro
      phosphorylation by a nuclear matrix-associated cyclic-nucleotide-independent
      kinase. The acute-phase response also caused an increased partitioning of p55
      with the nuclear matrix. It was concluded that, as a result of a molecular
      remodelling of the nuclear matrix at the point of contact with chromatin, the
      nature of its association with region II DNA changed during elevated haptoglobin
      gene expression.

PMID- 8979367
TI  - Albumin can reverse the release of potassium from human erythrocytes treated with
      the non-ionic detergent, Brij 58.
AB  - Exchange of erythrocyte intracellular (i/c) K+ for extracellular (e/c) Na+ in
      human erythrocytes treated with sub-CMC concentrations of the non-ionic detergent
      Brij 58 can be stopped by reincubation in serum or albumin containing solutions.
      The progressive equilibration of the K+ contents of detergent-treated human
      erythrocytes with the incubation medium was reversed by an albumin-mediated
      withdrawal of detergent molecules from the cell. Re-establishment of near normal
      [K+] in terms of K+/kg water proceeds in two ways: (i) a metabolism-dependent net
      accumulation of K+ ions; and (ii) a metabolism-independent shrinkage of
      erythrocytes, this being the more significant factor.

PMID- 8979369
TI  - Involution of mouse mammary glands during whole organ culture occurs via
      apoptosis of epithelial tissue.
AB  - Apoptosis was measured in mammary glands during whole organ culture, to determine
      whether regression resulting from hormone withdrawal results in epithelial cell
      death as in vivo involution. Glands were evaluated for morphology and DNA
      degradation prior to whole organ culture, after lobulo-alveolar development and
      2, 4, or 6 days after hormone withdrawal. The data indicated that mammary
      regression during whole organ culture mimics in vivo involution and results in
      part from apoptosis of epithelial tissue.

PMID- 8979370
TI  - Nuclear antigens, as DNA, of DSB389 MAb and some other anti-desmin monoclonal
      antibodies.
AB  - The anti-desmin monoclonal antibodies (MAbs) DSB389, AC54, and DSB860 recognize
      intermediate filaments (IFs) and nuclear antigens that appear granular, locate
      around chromosomes, and are insoluble following 0.5% Triton X-100 and
      cetyltrimethylammonium bromide (CTAB) extraction. Nuclear antigens of the MAbs
      were searched for in an IFs-deficient clone of SW13 cells. Reactive materials
      specific to DSB389, AC54, and DSB860 MAbs were trapped at the top of the gel of
      SDS-agarose-PAGE. The reactivity of the materials disappeared after treatment
      with DNase I. The reactivity, or trapping of this material at the top of the gel,
      required previous heat treatment of the sample before application to the gel. The
      MAbs recognized both single-stranded and double-stranded DNA in ELISA. These
      results indicate that at least the main nuclear antigens of DSB389, DSB860 and
      AC54 MAbs are DNA.

PMID- 8979371
TI  - Production of biologically active human RelA (p65) in baculovirus-infected insect
      cells.
AB  - A recombinant baculovirus was constructed to express a cDNA encoding RelA (p65),
      a member of the NF-kappa B/Rel family of proteins. Infection of Spodoptera
      frugiderda insect cells with the recombinant baculovirus resulted in the
      production of the biologically active protein as measured by immunoblotting using
      RelA-specific antisera and by electrophoretic mobility shift assays. The
      recombinant protein bound specifically to an oligonucleotide containing the NF
      kappa B consensus motif but not to that containing the unrelated Oct-1 consensus
      motif. Thus insect cell-derived RelA possess properties similar to the native
      protein and may be used in physical, biochemical, and pharmacological studies.

PMID- 8979372
TI  - Phylogenetic relationships in A-genome species of rice as revealed by RAPD
      analysis.
AB  - In order to clarify the phylogenetic relationships in A-genome species of rice,
      RAPD analysis was carried out using 29 accessions (8 Oryza sativa, 6 O.
      glaberrima, 13 O. perennis, and 2 O. breviligulata). Their total DNA was used as
      template for PCR with 14 decamer primers. The amplified products were
      electrophoresed in agarose gel, and the banding patterns were observed. Average
      number of total amplified bands for each accession using 14 primers was 84.6. By
      comparing the banding patterns, the proportion of common bands between 29
      accessions was calculated and a dendrogram showing genetic relationships was
      constructed. Most of the accessions formed clusters corresponding to their
      taxonomic grouping. The Oceanian and African forms of O. perennis were
      substantially different from all other groups. The Asian form of O. perennis,
      however, formed a complex with O. sativa while O. breviligulata was clustered
      with O. glaberrima. This indicates that O. sativa and O. glaberrima have probably
      originated from the Asian form of O. perennis and from O. breviligulata,
      respectively.

PMID- 8979373
TI  - Population genetics of cultivated common buckwheat, Fagopyrum esculentum Moench.
      X. Diffusion routes revealed by RAPD markers.
AB  - Diffusion routes of common buckwheat were investigated by constructing
      phylogenetic trees based on variability of RAPD markers among 46 land races and
      two natural populations of the ancestor. Thirty two primers out of 40 generated
      reliable RAPD bands, 295 in total. The percentage of polymorphic bands was the
      highest (45.9%) in southern China, the region in which buckwheat originated, and
      it declined sharply from southern China to the peripheral range of buckwheat
      cultivation. Phylogenetic trees for land races were constructed from RAPD
      variability by the unweighted pair group (UPG) and neighbors joining (NJ)
      methods. They suggest two major routes of diffusion of buckwheat cultivation; one
      from southern China-->northern China-->Korea-->Japan, the other from southern
      China-->Bhutan-->Nepal-->Kashmir-->Karakoram and the Hindukush.

PMID- 8979374
TI  - Comparative study of rbcL gene sequences in Fagopyrum and related taxa.
AB  - Four species of Fagopyrum, two species of Persicaria and one species of Rumex
      were analyzed for the DNA sequences of their rbcL genes. In addition to these
      seven species, we analyzed the published or available sequence data of ten
      related taxa in Polygonales, Plumbaginales and Caryophyllales. By estimating the
      base substitution rate between each pair of species, and by constructing
      phylogenetic trees we concluded that: 1) In Fagopyrum, F. cymosum and F.
      tataricum are much more closely related than expected previously; this confirms
      the conclusion of Kishima et al. (1995). 2) The new classification of Fagopyrum
      species proposed by Ohnishi and Matsuoka (1996) based on morphology, isozyme and
      cpDNA variability is consistent with the rbcL sequences. 3) The Polygonales and
      the Plumbaginales should be separated from the Caryophyllales as concluded by
      Giannasi et al. (1992). 4) The separation of Fagopyrum from other genera in the
      Polygoneae has a solid molecular basis.

PMID- 8979375
TI  - Control of the availability of exogenous 5-aminolevulinic acid in Escherichia
      coli.
AB  - We observed novel phenomena on the growth of a hemA deletion mutant (H500) of
      Escherichia coli: First, H500 cells grown in rich medium required an increased
      amount of exogenous 5-aminolevulinic acid (ALA) for normal growth, as compared
      with cells grown in poor medium. Second, H500 cells grown with an insufficient
      supply of ALA had a prolonged lag phase but relatively normal growth during the
      logarithmic phase. An increased requirement of exogenous ALA in rich media was
      due to an impermeability of the cells to ALA, resulting in a reduced ability to
      synthesize porphyrins. The latter could be also explained by change in
      permeability that was repressed under heme-deficient conditions.

PMID- 8979376
TI  - hiiragi, a gene essential for wing development in Drosophila melanogaster,
      affects the Notch cascade.
AB  - A recessive mutation, hiiragiP1, on the second chromosome of Drosophila was
      obtained by P element insertion mutagenesis. Flies homozygous for hiiragiP1 have
      notched wing margins. Genetic interactions between hiiragi and the genes that
      encode components of Notch signaling, such as Notch, Hairless, Serrate and
      deltex, strongly support the involvement of hiiragi in the signal transduction
      cascade of Notch. It has been reported that Serrate and Delta, other components
      of Notch signaling, share EGF-like repeats and a second conserved cysteine-rich
      motif, and that these components interact physically with the same region of
      Notch. In hiiragiP1; SerrateD/+ double mutants, we observed synergistic
      enhancement of the notched phenotype of wing margins. In contrast, Delta FX3 had
      no phenotypic effect on hiiragiP1 in hiiragiP1; Delta FX3/+ double mutants. Taken
      together, these results indicate that hiiragi is involved in the Notch signaling
      cascade induced by Serrate rather than by Delta.

PMID- 8979378
TI  - New DNA data collected and processed at DNA data bank of Japan.

PMID- 8979377
TI  - The SLGs corresponding to the same S24-haplotype are perfectly conserved in three
      different self-incompatible Brassica campestris L.
AB  - We have identified three strains of the same S24-haplotype in self-incompatible
      B. campestris L. Two of them, S-12j and 1-1j, have been derived from Japanese
      populations and one, 27-1t, from Turkish one. The cDNA clones of SLG24 (S24-locus
      glycoprotein), which linked to the S-locus, were isolated from each strain, and
      sequenced. Each clone isolated from S-12j, 1-1j and 27-1t, was designated as
      SLG24 (S-12j), SLG24 (1-1j) and SLG24 (27-1t), respectively. Their nucleotide
      sequences were completely identical in coding region, 5' non-coding region, and
      3' non-coding region, though the position of the polyadenylation site was
      slightly different among the cDNA clones. This result suggests that the origin of
      S24-haplotype in these three strains might be common, and that the nucleotide
      sequences of SLG24 of the same S24-haplotype are completely conserved among
      different populations. The high conservation of the SLG24 nucleotide sequences is
      probably essential for the recognition of self or non-self of self
      incompatibility in this S24-haplotype.

PMID- 8979379
TI  - The "self digest": self-knowledge serving self-regulatory functions.
AB  - Self-knowledge is conceptualized as a self digest that summarizes one's relations
      to the world and the personal consequences of these relations. It is a handy
      sourcebook that serves self-regulatory functions. It is distinguished from the
      classic notion that self-knowledge contains one descriptive actual self. The self
      digest contains information about three kinds of actual selves that differ in
      self-regulatory function: (a) an instrumental self, (b) an expectant self, and
      (c) a monitored self. It represents not only the actual self but desired (and
      undesired) selves that reflect different kinds of self-regulatory focus (i.e.,
      promotion or prevention). It represents not only one's own standpoint but also
      the standpoint of others whose beliefs one is motivated to take into account.
      This self-regulatory perspective is used to reconsider self-esteem, self
      enhancement, self-consistency, self-presentation, and cross-cultural differences
      in the self.

PMID- 8979380
TI  - Improving memory in old age through implicit self-stereotyping.
AB  - This research demonstrates that subliminally activated stereotypes can alter
      judgments about oneself and can change cognitive performance. In the first study,
      an intervention that activated positive stereotypes of aging without the
      participants' awareness tended to improve memory performance, memory self
      efficacy, and views of aging in old individuals; in contrast, an intervention
      that activated negative stereotypes of aging tended to worsen memory performance,
      memory self-efficacy, and views of aging in old participants. A second study
      demonstrated that for the strong effects to emerge from the shifting stereotypes,
      the stereotypes must be important to one's self-image: Young individuals randomly
      assigned to the same conditions as the old participants in the first study did
      not exhibit any of the significant interactions that emerged among the old
      participants. This research highlights the potential for memory improvement in
      old individuals when the negative stereotypes of aging that dominate the American
      culture are shifted to more positive stereotypes.

PMID- 8979381
TI  - Eliciting facial affect, motivation, and expectancies in transference:
      significant-other representations in social relations.
AB  - Recent research has demonstrated transference in social perception, defined in
      terms of memory and schema-triggered evaluation in relation to a new person (S.
      M. Andersen & A. B. Baum, 1994; S. M. Andersen & S. W. Cole, 1990; S. M.
      Andersen, N. S. Glassman, S. Chen, & S. W. Cole, 1995). The authors examined
      schema-triggered facial affect in transference, along with motivations and
      expectancies. In a nomothetic experimental design, participants encountered
      stimulus descriptors of a new target person that were derived either from their
      own idiographic descriptions of a positively toned or a negatively toned
      significant other or from a yoked control participant's descriptors. Equal
      numbers of positive and negative target descriptors were presented, regardless of
      the overall tone of the representation. The results verified the memory effect
      and schema-triggered evaluation in transference, on the basis of significant
      other resemblance in the target person. Of importance, participants' nonverbal
      expression of facial affect when learning about the target person (i.e., at
      encoding) reflected the overall tone of their significant-other representation
      under the condition of significant-other resemblance, providing strong support
      for schema-triggered affect in transference, through the use of this unobtrusive,
      nonverbal measure. Parallel effects on interpersonal closeness motivation and
      expectancies for acceptance/rejection in transference also emerged.

PMID- 8979382
TI  - Self-esteem and "if . . . then" contingencies of interpersonal acceptance.
AB  - The degree to which an individual perceives interpersonal acceptance as being
      contingent on successes and failures, versus relatively unconditional, is an
      important factor in the social construction of self-esteem. The authors used a
      lexical-decision task to examine people's "if. . . then" expectancies. On each
      trial, participants were shown a success or failure context word and then they
      made a word-nonword judgment on a second letter string, which sometimes was a
      target word relating to interpersonal outcomes. For low-self-esteem participants,
      success and failure contexts facilitated the processing of acceptance and
      rejection target words, respectively, revealing associations between performance
      and social outcomes. Study 2 ruled out a simple valence-congruency explanation.
      Study 3 demonstrated that the reaction-time pattern was stronger for people who
      had recently been primed with a highly contingent relationship, as opposed to one
      based more on unconditional acceptance. These results contribute to a social
      cognitive formulation of the role of relational schemas in the social
      construction of self-esteem.

PMID- 8979383
TI  - Stability within the self: a longitudinal study of the structural implications of
      self-discrepancy theory.
AB  - Self-discrepancy theory emphasizes the emotional significance of patterns of
      relations between the self-concept and ideal and ought self-guides and predicts
      stability within the self related to structural characteristics independent of
      specific self-beliefs. It was hypothesized that whereas participants' specific
      self-descriptions would vary substantially over time, magnitude of self
      discrepancy, regulatory focus (the individual's dominant self-guide domain), and
      other structural features would be stable. Participants (N = 47) were recruited
      from 2 samples that had completed a self-belief interview and a childhood memory
      cued-recall task 3 years earlier (T. J. Strauman, 1990). As expected,
      participants' self-descriptions varied, but magnitude and type of self
      discrepancy, associations between self-guide domains and childhood memories, and
      correlates of regulatory focus were stable.

PMID- 8979384
TI  - The self-fulfilling nature of positive illusions in romantic relationships: love
      is not blind, but prescient.
AB  - It is proposed that satisfying, stable relationships reflect intimates' ability
      to see imperfect partners in idealized ways. In this study of the long-term
      benefits (or possible costs) of positive illusions, both members of dating
      couples completed measures of idealization and well-being 3 times in a year. Path
      analyses revealed that idealization had a variety of self-fulfilling effects.
      Relationships were most likely to persist-even in the face of conflicts and
      doubts-when intimates idealized one another the most. Intimates who idealized one
      another more initially also reported relatively greater increases in satisfaction
      and decreases in conflicts and doubts over the year. Finally, individuals even
      came to share their partners' idealized images of them. In summary, intimates who
      idealized one another appeared more prescient than blind, actually creating the
      relationships they wished for as romances progressed.

PMID- 8979385
TI  - Self-definition, defensive processing, and influence: the normative impact of
      majority and minority groups.
AB  - Past research has found that recipients agree with majority group positions and
      resist minority group positions on direct measures of influence. The authors
      suggest that these attitude shifts reflect normative pressures to align with
      valued majorities and to differentiate from derogated minorities. In support of
      this idea, participants who considered a majority group relevant to their own
      self-definitions (but not those who judged it irrelevant), on learning that the
      group held a counterattitudinal position, shifted their attitudes to agree with
      the source. In a second study, recipients who judged a minority group
      (negatively) self-relevant, on learning that the group held a similar attitude to
      their own, shifted their attitudes to diverge from the source. These shifts in
      attitudes were based on participants' interpretations of the attitude issues.

PMID- 8979386
TI  - Selective self-stereotyping.
AB  - In an examination of group members' responses to the threat of negative in-group
      characterizations, sorority/fraternity members were asked to rate themselves,
      their own sorority/fraternity, sororities/ fraternities in general, and students
      in general on attributes that were stereotypic of sororities/ fraternities.
      Results showed that individuals selectively self-stereotyped-they embraced
      positive stereotypes as highly descriptive of themselves and their closest in
      groups but rejected negative stereotypes. They did not, however, deny that
      negative stereotypes were accurate or valid-they continued to accept them as
      typical of sororities/fraternities in general. This represents a protective,
      creative response to the threat posed by exposure to negative group attributes,
      in which self-stereotyping as a result of self-categorization is selective rather
      than complete.

PMID- 8979387
TI  - Big fish in small ponds: a social hierarchy analysis of intergroup bias.
AB  - High- and low-self-esteem group members received feedback about their individual
      performance as well as that of their own group and an out-group. They then
      evaluated both groups. Yoked-control observer individuals also provided group
      evaluations. In the in-group success/out-group failure condition, in-group
      enhancement tendencies were attenuated by individual failure feedback and
      augmented by individual success feedback. Low-self-esteem group members who
      received individual failure feedback showed favoritism toward the unsuccessful
      out-group over their own successful in-group. In the in-group failure/out-group
      success condition, in-group enhancement tendencies were attenuated by individual
      success feedback and augmented by individual failure feedback. Thus individuals'
      position in a social hierarchy mediates upward and downward social mobility
      strategies.

PMID- 8979388
TI  - Intergroup norms and intergroup discrimination: distinctive self-categorization
      and social identity effects.
AB  - Manipulation of in-group and out-group norms of discrimination and fairness
      allowed for the operation of competing social identity principles concerning in
      group bias, conformity, and group distinctiveness. The combined effects of these
      principles on in-group bias were first examined in a modified minimal-group
      setting (Study 1). Results demonstrated that participants' allocation strategies
      were in accord with the in-group norm. Furthermore, dissimilar norms resulted in
      greater use of positive differentiation allocation strategies. However, in
      natural groups (Study 2), more in-group bias was found when both group norms were
      similar and discriminatory. The results confirm the importance of in-group norms
      and demonstrate differences between experimental and natural groups in the
      applicability of competing social identity and self-categorization principles.

PMID- 8979389
TI  - Still participating after all these years: a study of life task participation in
      later life.
AB  - The authors examined in 618 older Americans the extent to which individual levels
      of life satisfaction were connected to participation in the shared tasks of late
      adulthood (e.g., community service and social life participation). Participation
      in these shared tasks was an important predictor of life satisfaction,
      controlling for health, self-reported vitality, social support, individual
      differences in congeniality, organizational affiliation, and prior levels of
      satisfaction. Social life participation was particularly important for retirees
      in predicting life satisfaction, more so than for study participants who were
      still able to derive enjoyment from work activity. This difference between
      retired and nonretired subjects was especially pronounced for men and illustrates
      how the important domains of activity shift with sociocultural expectations and
      opportunities of a given life phase.

PMID- 8979390
TI  - Why do bad moods increase self-defeating behavior? Emotion, risk taking, and self
      regulation.
AB  - Increased risk taking may explain the link between bad moods and self-defeating
      behavior. In Study 1, personal recollections of self-defeating actions implicated
      bad moods and resultant risky decisions. In Study 2, embarrassment increased the
      preference for a long-shot (high-risk, high-payoff) lottery over a low-risk, low
      payoff one. Anger had a similar effect in Study 3. Study 4 replicated this and
      showed that the effect could be eliminated by making participants analyze the
      lotteries rationally, suggesting that bad moods foster risk taking by impairing
      self-regulation instead of by altering subjective utilities. Studies 5 and 6
      showed that the risky tendencies are limited to unpleasant moods accompanied by
      high arousal; neither sadness nor neutral arousal resulted in destructive risk
      taking.

PMID- 8979391
TI  - Individuality and relatedness of the self: an autophotographic study.
AB  - Using R. C. Ziller's (1990) method of autophotography, the authors studied the
      duality of relatedness and individuality. A total of 226 young adults used photos
      (and words) to portray "who they are". Photo essays were scored for objective
      codes (e.g., people touching) and subjectively rated for individuality (richness
      of self-depiction). As predicted, persons who emphasized their personal rather
      than social identity depicted greater individuality; relatedness was associated
      with social and collective identity. Other results replicated earlier gender
      differences in relatedness and associations of individuality and relatedness with
      the 5-factor model. In the 2nd wave of the sample, individuality was associated
      with higher ego development, maturity, and self-directed values; low
      individuality was associated with restrictive conformity and security values. The
      authors suggest that the combination of individuality and relatedness is optimal
      for human development.

PMID- 8979392
TI  - The working self-concept in transference: significant-other activation and self
      change.
AB  - This research tested the hypothesis that changes in the working self-concept
      emerge in transference, defined as the activation and application of a
      significant-other representation to a new person and indexed by relevant
      inferences and memory (e.g., S. M. Andersen & A. Baum, 1994; S. M. Andersen, N.
      S. Glassman, S. Chen, & S. Cole, 1995). In an idiographic-nomothetic design,
      participants learned of a target person who resembled their own or a yoked
      participant's positively or negatively toned significant other. Results
      replicated the basic memory effect verifying transference. As predicted, the
      working self-concept changed in the transference condition. After learning about
      the new person, participants' freely listed self features shifted; the working
      self-concept became more infused with aspects of the self reflecting the self
      when with this significant other. Relevant changes in self evaluation were
      observed. Hence, changes in the working self-concept occurred in transference.

PMID- 8979393
TI  - Analysis of the promoter of the auxin-inducible gene, parC, of tobacco.
AB  - The auxin-responsive region (AuxRR) in the promoter of the parC gene was analyzed
      in transgenic tobacco plants in which the 5' flanking region of the parC promoter
      was placed upstream of the gene for beta-glucuronidase (GUS). The AuxRR was
      located between nucleotides (nt) -226 and -54. Detailed dissection of this
      segment revealed that the presence of the non-contiguous sequences from nt -226
      to -151 and from nt -84 to -54 was required for the expression of the auxin
      responsiveness of the parC promoter. The sequence from nt -226 to -151 was found
      to contain a sequence which resembles the as-1 element in the 35S promoter of
      cauliflower mosaic virus (CaMV). Although it has been reported that the as-1
      element is involved in auxin responsiveness [Liu and Lam (1994) J. Biol. Chem.
      269: 668], we showed that introduction of a point mutation into the as-1-like
      sequence completely eliminated auxin responsiveness, a result that suggests that
      the sequence is indispensable for auxin responsiveness. However, the presence of
      the as-1-like sequence alone was not sufficient for auxin responsiveness, since
      the segment (nt -226 to -84) that included the as-1-like sequence failed to
      confer auxin responsiveness on the core promoter. It is possible that the two
      separately located sequences play specific roles in interactions with trans
      factors that are required for the expression of the auxin responsiveness of the
      parC promoter.

PMID- 8979394
TI  - Partial characterization of a 17 kDa acidic protein, EFP, induced by
      thiocarbamate in the early flowering phase in Asparagus seedlings.
AB  - Asparagus officinalis seedlings treated with either thiocarbamates or carbamates
      are induced to flower within 2-3 weeks of application. SDS-PAGE and 2-D PAGE
      resolutions of total soluble proteins of treated seedlings showed the
      accumulation of an acidic 17 kDa polypeptide. Partial amino acid sequence of the
      acidic protein showed homology to the wound-responsive A. officinalis PR 1,
      AoPR1. We named this protein EFP, early flowering protein, owing to its advanced
      appearance during the early transition from vegetative to floral phase.
      Carbamates and thiocarbamates that induced more than 80% flowering rates
      corresponded with increased level of EFP while compounds that are weak flower
      inducers showed reduced amount of EFP. The observation thus defined the
      correlationship of EFP to variable flowering rates.

PMID- 8979395
TI  - cDNA cloning and expression of a gene for isocitrate lyase in pumpkin cotyledons.
AB  - A cDNA clone for isocitrate lyase (ICL) was isolated from a cDNA library prepared
      from the poly(A)+ RNA of etiolated pumpkin cotyledons. The cDNA encoded a
      polypeptide with 576 amino acids, whose sequence is more than 79% identical to
      those of ICL from other higher plants and contains the C-terminal tripeptide, Ser
      Arg-Met, which is a putative targeting signal to microbodies. Immunogold analysis
      revealed that ICL protein is exclusively localized in microbodies in etiolated
      pumpkin cotyledons. Double labeling experiments with protein A-gold particles of
      different sizes showed that ICL protein coexists with a leaf-peroxisomal enzyme,
      glycolate oxidase, in the microbodies of greening and senescing pumpkin
      cotyledons, indicating that transformation between glyoxysomes and leaf
      peroxisomes occurs directly during greening and senescence of the cotyledons.
      Immunoblot analysis showed that the amount of ICL protein increased markedly
      during germination and decreased rapidly when seedlings were exposed to
      illumination, which induced the microbody transition from glyoxysomes to leaf
      peroxisomes. In senescing cotyledons, the level of the ICL protein and ICL mRNA
      increased again with the reverse transition of microbodies from leaf peroxisomes
      to glyoxysomes. Changes in the amount of ICL protein did not correspond to the
      changes in the level of ICL mRNA during greening and senescence of the
      cotyledons, an indication that post-transcriptional regulation plays an important
      role in the microbody transition.

PMID- 8979396
TI  - Alterations in the biosynthesis of lignin in transgenic plants with chimeric
      genes for 4-coumarate: coenzyme A ligase.
AB  - The introduction of chimeric sense and antisense gene constructs for 4
      coumarate:coenzyme A ligase into tobacco plants caused the reduction of the 4CL
      activity in the transgenic plants. In the transgenic plants, the cell walls of
      the xylem tissue in stems were brown and the molecular structure of lignin in the
      colored cell walls was dramatically different from that in the control plants.
      Analysis with different types of stain revealed that levels of cinnamyl aldehyde
      residues and syringyl units in lignin were depressed in the brownish cell walls.
      Furthermore, the lignin content in colored tissue was lower than that in the
      normal tissue. Our results indicate that 4CL has important roles in the
      determination of the composition and the amount of lignin in tobacco plants.

PMID- 8979397
TI  - Two-dimensional protein patterns of Arabidopsis wild-type and auxin insensitive
      mutants, axr1, axr2, reveal interactions between drought and hormonal responses.
AB  - In order to detect gene products involved in Arabidopsis drought adaptive
      strategy, 2D-PAGE protein patterns of two auxin-insensitive mutants, axr1, axr2,
      differentially affected in specific drought responses, were compared to the wild
      type Columbia ecotype, in well-watered and drought-stressed conditions. Coupled
      to computer analysis of polypeptide amounts, 2D-electrophoresis revealed subtle
      changes in protein expression induced by progressive drought stress and/or
      mutations affecting the auxin response pathway. The differential protein patterns
      of axr1 and axr2 were consistent with their contrasting drought responses. The
      specific leaf and root protein patterns of axr1 showed that this mutation
      disrupts drought responses related to auxin regulation. In particular, the near
      absence of drought rhizogenesis in axr1 was associated with a root protein
      pattern closer to the well-watered than to the water-stressed axr2 and Columbia
      wild-type root protein patterns. Also, the largely different effects of axr1 and
      axr2 mutations suggest that they affect different pathways in auxin response.
      Several sets of polypeptides, whose regulation was affected by drought and/or
      mutation, were thus detected. These polypeptides could play a role both in the
      auxin and the drought response pathways. Their identification, through
      microsequencing, should be most informative.

PMID- 8979398
TI  - A lectin from leaves of Neoregelia flandria recognizes D-glucose, D-mannose and N
      acetyl D-glucosamine, differing from the mannose-specific lectins of other
      monocotyledonous plants.
AB  - A mannose-specific lectin was isolated from leaves of Neoregelia flandria, an
      ornamental plant that belongs to Bromeliaceae, a family of monocotyledons. The
      amino acid composition and molecular mass of the lectin were similar to those of
      mannose-specific lectins from other monocotyledons. However, in a test to examine
      the inhibition of hemagglutination, it became apparent that the isolated lectin
      recognized D-glucose and N-acetyl D-glucosamine in addition to D-mannose, unlike
      mannose-specific lectins from the monocotyledons that have been reported to date.

PMID- 8979399
TI  - Structure and expression of mitochondrial citrate synthases from higher plants.
AB  - Mitochondrial citrate synthase (EC 4.1.3.7) represents the first enzyme of the
      tricarboxylic acid cycle, catalyzing the condensation of acetyl-CoA and
      oxaloacetate, finally yielding citrate and CoA. We report here the isolation of
      cDNA clones encoding citrate synthase from Nicotiana tabacum, Beta vulgaris and
      Populus. Nucleotide and deduced amino acid sequences were compared with
      previously published sequences of mitochondrial citrate synthases from
      Arabidopsis thaliana and potato, as well as with the sequence of glyoxysomal
      citrate synthase from pumpkin. Homologies between the various plant mitochondrial
      enzymes were in the range from 77.2% (potato vs. Arabidopsis) to 94.2% (potato
      vs. tobacco) on the nucleotide level (coding regions only), and in the range from
      70.1% to 90.4% (potato vs. Arabidopsis, and potato vs. tobacco, respectively) on
      the amino acid level. Identities of the mitochondrial isozymes to the pumpkin
      glyoxysomal enzyme were below 30% on the nucleotide and amino acid level. In
      Northern blot experiments citrate synthase mRNA was detected in all tissues
      analyzed. However, levels of expression showed tissue dependency despite the fact
      that citrate synthase is usually considered a house-keeping enzyme. Whether these
      different levels of expression reflect tissue-specific variations with respect to
      basic metabolism awaits further analysis.

PMID- 8979400
TI  - The level of mRNA transcribed from psaL, which encodes a subunit of photosystem
      I, is increased by cytokinin in darkness in etiolated cotyledons of cucumber.
AB  - A cDNA clone for an mRNA whose level increased within 2 h of the start of
      treatment with N6-benzyladenine in etiolated cotyledons of cucumber was isolated
      by differential hybridization. The cDNA was homologous to psaL, which encodes
      subunit XI (PSI-L) of photosystem I. The accumulation of psaL mRNA was
      specifically induced by cytokinins or light.

PMID- 8979401
TI  - Prediction of blood lactate accumulation from excess CO2 output during constant
      exercise.
AB  - To determine the predictability of blood lactate accumulation from excess CO2
      output derived from bicarbonate buffering of lactic acid during constant
      exercise, eight normal active volunteers were studied during three stages of
      constant exercise on a cycle ergometer. Three work rates consisted of 100% (stage
      I), 120% (stage II) and 150% (stage III) of each subject's anaerobic threshold
      (AT), each of which was lasted for 4 min. Excess CO2 output (Ex CO2, ml) at each
      stage of constant exercise was estimated form the integral of difference between
      total VCO2 and aerobic VCO2 (from regression line for VCO2 and VO2 at exercise
      intensities below the AT obtained in incremental exercise test). Ex CO2 per body
      mass (Ex CO2-mass-1) was increased progressively with blood lactate (La)
      accumulation from rest to each stage of constant exercise. Mean values (+/-SD) in
      the measured La accumulation (delta La,measured) and predicted La accumulation
      (delta La,predicted) at three stages of constant exercise were 1.82 +/- 0.83 vs
      3.19 +/- 1.70 for stage 1, 5.58 +/- 3.47 vs 7.09 +/- 3.28 for stage II and 12.19
      +/- 2.36 vs 12.74 +/- 1.83 mmol.l-1 for stage III, respectively. There was a
      significant difference between delta La,measured and delta La,predicted at stage
      I (p < 0.05), but no significant differences between these two variables at stage
      II and III. The averaged difference from delta La,predicted to delta La,measured
      at stage III (0.55 mmol.l-1) showed a tendency to be smaller than stage I (1.38
      mmol.l-1) and II (1.50 mmol.l-1). On the other hand, delta La,predicted was found
      to correlate very closely with delta La,measured (r = 0.954, P < 0.001, n = 20).
      The results of this study suggest that the changes of La accumulation could be
      predicted from excess CO2 output generated in constant exercises above the AT.

PMID- 8979402
TI  - The effects of race, living standards, and exercise on the degree of motor
      development: comparison between schoolchildren in the Republic of Honduras and
      Japan.
AB  - To investigate the development of motor ability according to age and physique, a
      comparison was made among races and/or living standards of schoolchildren in
      Republic of Honduras, and between Honduran and Japanese schoolchildren. Based on
      the results of these comparisons, the extent to which exercise contributes to the
      development of motor ability was examined. Subjects were schoolchildren of
      typical three races in Honduras: Negroid, Mongoloid (native Indio), and mixed
      race (Mongoloid, Caucasoid, and Negroid), who attended public elementary schools.
      For a further comparison, schoolchildren of mixed race attending private schools,
      whose living standards are thought to be different from children attending public
      schools, were also selected. Comparing physique among races from the measurement
      values in the test battery, Negroid group ranked highest followed by the mixed
      race group and Mongoloid group. The results for the comparison of motor ability
      were also in the same order. From the viewpoint of living standards, the physique
      and motor ability of the private school children, who were from wealthy families,
      was better than that of the public school children. However, when the degrees of
      motor development were compared using revised values based on age and physique,
      the differences among groups became smaller, and there was no significant
      difference between groups in the 50-meter dash or in the standing long jump.
      However, a comparison with Japanese schoolchildren showed that, even if there was
      no difference in physique, Japanese schoolchildren were still superior in motor
      ability. These results suggest that differences in the degree of motor
      development are mainly due to differences in exercise experience.

PMID- 8979403
TI  - Antioxidant enzymes response to endurance exercise training and dietary proteins
      in rat skeletal muscle and liver.
AB  - This study was conducted to observe the effects of endurance exercise training on
      antioxidant enzyme activity in the liver and gastrocnemius muscle of rats being
      fed dietary casein and soy protein. The respective influences of dietary casein
      and soy protein on the activity of antioxidant enzymes were also compared. Thirty
      nine male Wistar rats, aged 3 weeks, were randomly assigned to six groups: a
      normal protein control group, a normal protein endurance training group, a casein
      protein control group, a casein protein endurance training group, a soy protein
      control group, and a soy protein endurance training group. The endurance exercise
      training groups were adapted to a treadmill for 2 weeks prior to the date the
      rats were forced to run for 60 min at 25 m/min, 5 days/week for 12 weeks. We
      found that antioxidant enzyme activity in the gastrocnemius muscle was neither
      effected by the dietary proteins (casein and soy protein) nor by the above
      endurance exercise training load. However, hepatic Cu,Zn-SOD activity increased
      significantly for the dietary casein and soy protein diet groups as compared with
      the normal protein diet group (P < 0.01). Furthermore, significant increases both
      in hepatic Cu,Zn-SOD activity in the normal protein group and hepatic GSHpx
      activity in the casein and soy protein groups were observed when rats were loaded
      with 25 m/min of endurance exercise training (P < 0.01). These results suggest
      that, under the above experimental conditions, a casein or soy protein diet
      increase hepatic Cu,Zn-SOD activity, while endurance exercise training is
      effective in increasing hepatic Cu;Zn-SOD activity on a normal protein diet and
      in increasing hepatic GSHpx activity for cysteine and methionine deficient diets.

PMID- 8979404
TI  - Physiological and psychological effects of head heating during rest and work.
AB  - The purpose of this study is to obtain some knowledge related to physiological
      and psychological effects of head heating by radiation on the vital body under
      varying conditions of the environmental temperature and physical activity. The
      study was proceeded with experiments 1 and 2 using 8 women, all in good health as
      subjects. In experiment 1, firstly the subject at rest was kept at an ambient
      temperature of 28 degrees C for 40 minutes. The, moving to a room kept at an
      ambient temperature of 18 degrees C or 28 degrees C, the state at rest was
      maintained with head heating at 3 radiant intensities (without radiation, 35
      degrees C and 40 degrees C of globe temperature) for a further 40 minutes. In
      experiment 2, continued from the same procedure of experiment 1, work on the
      ergometer was performed for 30 minutes with head heating at 2 radiant intensities
      (without radiation and 35 degrees C of globe temperature). Items measured were
      tympanic temperature, skin temperatures, heart rate, and subjective sensations.
      The principal results obtained are as follows: 1) Tympanic temperature, forehead
      skin temperature and score of thermal sensation of head increased, while the
      others decreased at 18 degrees C. 2) Decrease of scores was inhibited by head
      heating in finger skin temperature, toe skin temperature and heart rate. 3) When
      radiant intensities at 35 degrees C and 40 degrees C were compared, statistical
      significant difference was noted in forehead skin temperature only, the
      difference of radiant conditions gives a little effect to the vital body. 4)
      Effects brought by head heating during rest decreased owing to the addition of
      work.

PMID- 8979405
TI  - Alterations of fibrinolytic activity in human during and after hyperbaric oxygen
      exposure.
AB  - To clarify the stage of fibrinolytic activation by hyperbaric oxygen (HBO)
      exposure, we examined its alterations in human during and after the HBO exposure.
      Eight healthy female volunteers breathed oxygen at 284 kPa (2.8 atmospheres
      absolute). Blood samples were collected before compression, shortly after
      compression to the pressure 284 kPa, shortly before the start of decompression,
      shortly after decompression, and then again 3 hours after decompression. We
      estimated the euglobulin fibrinolytic activity (EFA) and, the activities and
      antigens of both tissue-type plasminogen activator (t-PA) and plasminogen
      activator inhibitor-1 (PAI-1). The PAI-1 activity and PAI-1 antigen showed
      significant decrease after compression to a pressure 284 kPa, before the start of
      decompression, and after decompression. The EFA level and t-PA activity rose
      significantly shortly after decompression, and 3 hours later returned on
      baseline. These findings suggest that fibrinolytic activity is elicited after HBO
      rather than during HBO.

PMID- 8979406
TI  - Effects of lights of different color temperature on the nocturnal changes in core
      temperature and melatonin in humans.
AB  - A variety of types of artificial illumination has recently become available,
      differing in the quality of illumination and range of color temperature. In our
      previous studies we found that in subjects with normal color vision the nocturnal
      fall in core temperature and the increase of urinary melatonin excretion were
      suppressed by bright blue or green light, but not by bright red or dim lights.
      The aim of our present study was to examine from the view point of chronobiology
      whether the lights of different color temperature often used in everyday life may
      affect core temperature and urinary melatonin secretion differently. Experiments
      were carried out on five subjects with normal color vision. They were exposed for
      5 hr (from 21:00 h to 2:00 h) to two kinds of bright (1000 lx) light of different
      color temperature (6500 K, 3000 K) with dim (50 lx) light as a control; after
      exposure they slept in darkness. Our main results were as follows: The light with
      a high color temperature of 6500 K more strongly suppressed the nocturnal fall of
      the core temperature and the nocturnal increase of melatonin secretion than the
      light with a low color temperature of 3000 K. This difference was particularly
      evident for core temperature during the sleep period following experimental
      illumination.

PMID- 8979407
TI  - Oral health week.
AB  - This article reports on the Oral Health Week held in December 1994 and focuses on
      an initiative by the BDA which organised dentists and volunteers from Age Concern
      in a project to look at oral health for the elderly. It examines the aims and the
      results of the week and draws some useful conclusions on improving the outcome if
      a project such as this were attempted again.

PMID- 8979408
TI  - Orofacial reactions after contact with latex gloves.

PMID- 8979409
TI  - Evidence based assessment.

PMID- 8979410
TI  - Treating restorative dentistry to health.

PMID- 8979411
TI  - Service quality in dentistry: the role of the dental nurse.
AB  - Patients judge the dental service they receive by the interaction with the
      service providers-the dentist and his or her staff-as they are unable to judge
      the technical quality of the service. To perform well as a service provider,
      employees such as dental nurses have to be well motivated and satisfied with
      their position. A study of the role of the dental nurse in contributing to
      service quality in dentistry was carried out through interviews with dentists and
      nurses at 20 dental practices in the South Thames region in 1995. The results
      revealed that while dental staff believed that the role of the dental nurse was
      important in terms of the patient's view of the practice, perceptions of the
      nurse's role differed. The majority of dentists felt that the nurse's role should
      be to anticipate their needs, while the nurses' opinions were evenly divided
      between putting the needs of the patient first or those of the dentist. Nurses
      also felt that their role was stressful and reported a lack of praise and
      recognition of their efforts by dentists. Few practices had written contracts or
      performance appraisals. The results indicated a lack of effective communication
      in many dental practices, producing role strain for the nurse and reducing job
      satisfaction. Increasing job satisfaction reduces staff turnover, resulting in
      more consistent service quality and reducing associated costs. In order to
      achieve this, several recommendations are made with the aim of improving
      communication between staff in dental practices.

PMID- 8979413
TI  - The single unit, single retainer, cantilever resin-bonded bridge.
AB  - Resin-bonded restorations have many advantages over conventional alternatives.
      Advances in adhesive technology together with a better understanding of the
      clinical function of such restorations have allowed resin-bonded bridges to play
      an important role in everyday clinical practice. This paper highlights the role
      and importance of the single abutment, single pontic cantilever resin-bonded
      bridge. Clinical experience might suggest that the cantilever design offers a
      viable alternative to other designs. Furthermore, the paper suggests that when
      cantilever resin-bonded bridges fail initially, re-bond often leads to
      predictable long-term success. Factors such as patient selection, abutment
      preparation, retainer design and the aesthetic limitations of resin-bonded
      bridges are also discussed. The authors can claim that further clinical studies
      are necessary to identify exactly what factors influence the success of
      cantilever and other resin-bonded designs.

PMID- 8979412
TI  - Decontamination of dental unit water systems: a review of current
      recommendations.
AB  - It is now recognised that water delivered to dental handpieces and air/water
      syringes via dental unit water systems may become significantly contaminated with
      micro-organisms which originate from the incoming water supply and, to a lesser
      extent, with oral micro-organisms. The purpose of this article is to review the
      literature relating to the risks associated with contamination of dental unit
      water systems and methods which may be used to minimise these risks.

PMID- 8979414
TI  - Adenomatoid odontogenic tumour: an unusual cause of gingival swelling in a 3-year
      old patient.
AB  - The adenomatoid odontogenic tumour (AOT) is an uncommon, benign lesion of the
      jaws. It has been subdivided into two broad categories: central AOT and
      peripheral AOT. A case of peripheral AOT in a 3-year-old female with a history of
      congenital adrenal hyperplasia is reported. The lesion presented as a gingival
      mass associated with a fully erupted deciduous canine tooth. This is the eleventh
      reported case of peripheral AOT and the first in a 3-year-old patient.

PMID- 8979415
TI  - Guidelines for the selection, use, and maintenance of visible light activation
      units.
AB  - New light-cured dental materials are constantly being developed and marketed in
      response to the increasing demand for aesthetic dentistry. Therefore light
      activation units are now a standard item of equipment in everyday dental
      practice. Many factors are involved in the selection of a light unit and among
      these is the need for the unit to polymerise light-activated resin restorations
      effectively. This article reviews recent developments in the design of visible
      light activation units and outlines the desirable features such units should
      possess. In addition, factors influencing the effectiveness of light-activation
      units are discussed and recommendations made regarding their routine testing, use
      and maintenance.

PMID- 8979416
TI  - Surveillance of the complications of blood transfusion.

PMID- 8979417
TI  - Unpasteurised apple juice causes outbreak of haemolytic uraemic syndrome in North
      America.

PMID- 8979418
TI  - Paediatric surveillance in the British Isles.

PMID- 8979419
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 8979420
TI  - Subunit vaccines for complex tick-borne pathogens: dream or reality?

PMID- 8979421
TI  - Prospects for subunit vaccines against tick-borne diseases.
AB  - Tick-borne parasites are a serious impediment to the improvement of live-stock
      production in the developing world. The major parasites affecting cattle include
      Theileria parva, T. annulata, Babesia bigemina, B. bovis, Anaplasma marginale and
      Cowdria ruminantium. The control of these infections is dependent on the use of
      acaricides to decrease transmission by the tick vectors, and immunization of
      susceptible animals with live vaccines. The use of acaricide is hampered by the
      development of resistance, and live vaccines require cold chain facilities, which
      are generally unreliable in developing countries. There is therefore a need for
      improved vaccines that can circumvent these problems. There is a subunit vaccine
      being developed for T. parva based on the major surface antigen of the sporozoite
      (p67). A similar antigen, SPAG 1, has been identified as a candidate for T.
      annulata. Although several candidate antigens have been identified for Babesia
      spp., progress towards development of a subunit vaccine based on these antigens
      has been hampered by polymorphism among isolates and between species, and lack of
      knowledge of the immune effector mechanisms responsible for protection. The
      search for protective antigens of A. marginale has focused on outer membrane
      proteins; immunization with a variety of these antigens alone or in combination,
      has yielded promising results. As with Babesia, further definition of immune
      effector mechanisms is needed to optimize immunization strategies. The work on
      identifying the protective antigens of C. ruminantium is in its embryonic stages;
      however, two antigens have been identified and are currently being evaluated.
      There is high expectancy for subunit vaccines for all these diseases; however
      there is need for further work to elucidate the immune mechanisms in order to
      select appropriate antigen delivery systems.

PMID- 8979423
TI  - Thyroid status and adenosine triphosphatase activity in experimental Trypanosoma
      congolense infection in rabbits.
AB  - The effect of trypanosome infection on the plasma levels and ratios of tri
      iodothyronine (T3) and thyroxine (T4) as well as the activity of mitochondrial
      adenosine triphosphatase (ATPase) were investigated. Three groups of sexually
      mature white New Zealand rabbits were used. Group 1 consisted of the normal non
      infected rabbits, group 2 were experimentally infected with Trypanosoma
      congolense and group 3 were infected but given replacement doses of thyroxine.
      The infected animals (group 2) showed a rapid decline in both T3 and T4 but an
      increase in the T3/T4 ratio indicating differential production or clearance rates
      between the two hormones. The mitochondrial ATPase activity was found to be
      depressed in the infected group whereas there was no significant difference in
      the ATPase activity between the non-infected (group 1) and infected-treated
      animals (group 2). It is postulated that trypanosome induced hypothyroid status
      may play a role in the impairment of mitochondrial ATPase activity, a key enzyme
      in energy metabolism.

PMID- 8979422
TI  - Alpha 2 adrenoceptor agonists in the horse--a review.
AB  - In recent years the usefulness of the alpha 2 adrenoceptor agonist drugs has been
      recognized in equine practice. Several agents have become available and are now
      licensed for use in a number of countries. The principle actions of all alpha 2
      adrenoceptor agonists are similar, in that they produce a reduction in heart rate
      and alteration of heart rhythm, an initial hypertension followed by a prolonged
      hypotension, a decrease in the cardiac output and respiratory depression. For
      clinical purposes, these agents produce sedation and analgesia, they are useful
      for premedication and markedly potentiate the effects of other sedative/analgesic
      agents. Differences in receptor specificity between the alpha 2 adrenoceptor
      agonists results in the distinguishing characteristics of the individual agents,
      particularly with respect to their duration of action, sedative effect and
      analgesic properties; their cardiopulmonary effects are however similar, when
      equipotent sedative doses are administered. When used in combination with other
      agents, the alpha 2 adrenoceptor agonists all appear to act in a similar manner,
      with the greatest difference being related to their duration of action.

PMID- 8979424
TI  - A case report and review: the gross, histological and immunohistochemical
      characteristics of a carcinoma of ectopic thyroid in a dog.
AB  - Neoplasms of the canine thyroid gland represent 5-10% of heart base masses
      (Capen, 1978). Ectopic thyroid tissue is detected most commonly in the thorax,
      with 23-80% of all dogs having ectopic tissue at the base of the heart (Leav et
      al., 1976; Walsh & Diters, 1984). We describe here the gross and microscopic
      features of a rare ectopic thyroid carcinoma in a dog and the results of an
      immunohistochemical study of the tumour.

PMID- 8979425
TI  - Post-natal changes in biliary lipids in suckling goat kids.
AB  - The post-natal composition of biliary lipids in the bile of suckling goat kids
      has been studied during the first month of life. Samples of hepatic and vesicular
      bile were obtained from animals fed with milk. Bile flow increased with age and
      the concentration of bile acids also rose up to 14 days of age. Cholesterol
      reached maximum values immediately after birth and then decreased. Bile acids
      conjugated with taurine predominated and this pattern of preferential
      tauroconjugation persisted at all ages, as has also been found in carnivores and
      sheep. Comparison of vesicular and hepatic bile composition revealed a poor
      concentration capacity of the gallbladder in pre-ruminant kids.

PMID- 8979426
TI  - Arthrosonography--the use of diagnostic ultrasound in septic and traumatic
      arthritis in cattle--a retrospective study of 25 patients.
AB  - The case records, clinical, radiographic, ultrasonographic and arthrocentesis
      findings from 25 cattle with septic or traumatic arthritis were reviewed. The
      total of 30 joints involved were: articulatio cubiti (elbow joint)-1, articulatio
      carpi (carpal joint)-10; articulatio genus (stifle joint)-4, articulatio
      tarsocruralis (tarsocrural joint)-8; articulatio metacarpo-/metatarsophalangea
      (metacarpo-/metatarsophalangeal joint -7. Ultrasonographic investigation was
      performed using 7.5 MHz linear and 5 MHz sector transducers. In eight cattle, a
      concurrent infection of periarticular tendon sheaths or hygroma was diagnosed.
      The distension of the joint cavities could be imaged in all cases. Assessing
      echogenicity, acoustic enhancement, ultrasonographic character of the exudate
      (liquid or clotted) and findings revealed by aspiration, arthrotomy or at
      necropsy, the synovial effusion was classified as: serous, fibrinous or fibrino
      purulent. Diagnostic ultrasound provided a comprehensive preoperative diagnosis
      in septic and traumatic arthritis by imaging the accurate localization of soft
      tissue swelling and the extent and consistency of joint effusion.

PMID- 8979427
TI  - Evaluation of a nutritive oral rehydration solution for the treatment of calf
      diarrhoea.
AB  - The essential constituents of a conventional oral rehydration solution (ORS) are
      sodium, glucose and a bicarbonate precursor. The glucose promotes sodium uptake
      but because these solutions are isotonic, it is insufficient to sustain calorie
      requirements. This paper examines the performance of a novel ORS with over three
      times the conventional glucose concentration, by comparing it with two leading
      commercial ORSs in calves with induced Escherichia coli diarrhoea. This solution
      showed greater ability than the current market-leading ORS to repair
      extracellular fluid and plasma volume and to correct both hyponatraemia and
      metabolic acidosis, especially in more severely affected calves. In acidotic
      calves it was more effective in correcting hyperkalaemia, probably by supplying
      glucose to promote cellular potassium uptake as well as by correcting the
      acidosis. It therefore appears possible to depart from the traditional isotonic
      formulations for calf ORSs and gain significant nutritional support while
      retaining effective rehydration and correction of acid-base and electrolyte
      disturbances. This seems especially important in young animals where energy
      deprivation imposes a particular penalty; the use of hypertonic ORSs should not,
      however, be extended to other species without further research.

PMID- 8979428
TI  - Possible roles for prolactin, thyroxine and insulin in the growth of heifers
      before and during early pregnancy.
AB  - Two groups of British Friesian heifers with cyclic ovarian function and the
      potential for further growth were individually fed a restricted diet at two
      levels over a 12-week period. Eight heifers receiving the higher level of feed
      (SP group) and five receiving the lower level (LP group) became pregnant by
      artificial insemination at week 6. Mean (and SEM) body weight changes in the SP
      and LP groups were respectively 0.24 (+/- 0.024) kg day-1 and -0.19 (+/- 0.039)
      kg day-1. Over the period from weeks 3-12, mean concentrations of plasma
      prolactin, thyroxine and insulin in the five LP heifers were 39%, 67% and 74%,
      respectively, of those in the eight SP heifers. The results suggest that
      prolactin, thyroxine and insulin have roles in the growth of heifers before and
      during early pregnancy.

PMID- 8979429
TI  - Bruising and biochemical measures of stress, dehydration and injury determined at
      slaughter in sheep transported from farms or markets.

PMID- 8979430
TI  - Hemophilus influenzae septic arthritis and pneumonia in an adult as the first
      presentation of multiple myeloma.
AB  - We describe an apparently healthy woman who presented with monoarthritis of the
      right knee and a history of respiratory infection. The synovial fluid cultures
      grew beta lactamase-negative H. influenzae. Chest roentgenogram showed patchy
      densities throughout the right lung. Investigations for a predisposing factor for
      this H. influenzae infection revealed underlying multiple myeloma. As H.
      influenzae pyoarthrosis is extremely rare in adults, we suggest that an
      underlying systemic cause be sought in all such patients.

PMID- 8979432
TI  - Case report: autosomal dominant polycystic kidney disease.

PMID- 8979431
TI  - Management protocol for an enhancing cerebral lesion in HIV infection.

PMID- 8979433
TI  - Oral ganciclovir: role in maintenance therapy for CMV retinitis in AIDS patients.

PMID- 8979435
TI  - The more the merrier.

PMID- 8979434
TI  - The rationale for naltrexone therapy as an alternative to methadone treatment for
      opiate addiction.

PMID- 8979436
TI  - Genetic instability and tumorigenesis: introduction.

PMID- 8979437
TI  - Genomic stability and instability: a working paradigm.

PMID- 8979438
TI  - Surveillance and genome stability in budding yeast: implications for mammalian
      carcinogenesis.

PMID- 8979439
TI  - Genomic instability and its role in neoplasia.

PMID- 8979440
TI  - Role of DNA excision repair gene defects in the etiology of cancer.

PMID- 8979441
TI  - Chromosome instability syndromes: lessons for carcinogenesis.

PMID- 8979442
TI  - Genetic alterations in human tumors.

PMID- 8979443
TI  - Hormone replacement therapy.

PMID- 8979444
TI  - Corticosteroid-induced osteoporosis.

PMID- 8979445
TI  - Penicillin allergy.

PMID- 8979446
TI  - Inequities in health and the region of the Americas.

PMID- 8979447
TI  - Centers for Disease Control (CDC) in the United States: 50 years.

PMID- 8979448
TI  - Elimination of leprosy in the Americas.

PMID- 8979449
TI  - Partial relaxation of diaphragm and lung function parameters.
AB  - The present study investigates the effect of partial relaxation of diaphragm on
      the lung functions in the absence of active lung and neuromuscular disorders.
      Comprehensive functional tests of the breathing was performed on 22 subjects with
      partial relaxation of the diaphragm (elevated hemidiaphragm) found during an X
      ray study on the occasion of gastrointestinal disorder. On the basis of the
      results of two group of patients, one with ventilatory disorders (n = 9-4 men and
      5 women) and another with normal lung ventilation (n = 13-7 men and 6 women) the
      conclusion was drawn that in the absence of additional pathology the partial
      relaxation of the diaphragm does not causes any changes in the lung function
      parameters with the exception of the tendency towards low values of the
      parameters for the respiratory muscle strength (PImax and PEmax).

PMID- 8979450
TI  - Algorithm of diagnostic invasive sonography.
AB  - An algorithm developed for diagnostic invasive sonography is presented. It was
      used in examining 350 patients. 385 manipulations were performed under ultrasound
      control in relation to 371 pathologic objects. A technical efficiency ranging
      from 97 to 100% was achieved for the various manipulations. This algorithm helps
      in finding the specific approach to each case on the basis of clinical data
      available, the characteristic of the pathologic object, and its localisation by
      organs and regions thus avoiding any risks and complications and achieving the
      planned target for the chosen manipulation.

PMID- 8979451
TI  - Relationship between somatotype and some risk factors for ischemic heart disease.
AB  - The study included 635 practically healthy male subjects aged 20-60 years
      employed in the Plovdiv Region. Using the Heath-Carter method we differentiated
      among them the following somatotypes: endomorphic (135), mesomorphic (157),
      ectomorphic (26) and subjects not matching any somatotype and lying outside the
      typological diagram (317). The analysis of the relationship between the
      somatotypes and some risk factors for ischemic heart disease (IHD) (cholesterol,
      arterial blood pressure, body mass, and body mass index) revealed the following
      peculiarities: the subjects lying outside the typological diagram showed the
      greatest predisposition for developing IHD followed by the endomorphic and
      mesomorphic groups. The risk for IHD in the ectomorphic group was negligible.
      Arterial hypertension was found in 48% of the subjects having the type lying
      outside the typological diagram, 31% in the endomorphic and mesomorphic groups.
      None of the ectomorphic subjects had elevated arterial pressure. Increased risk
      due to high cholesterol levels was established in the subjects outside the
      diagram-56.6%, while in the remaining groups it was 46%. The mean levels of
      triglycerides and low density lipoproteins had critical values in the subjects
      outside the typological diagram while the high density lipoprotein levels were
      the most elevated in the subjects of ectomorphic type.

PMID- 8979452
TI  - The ulcer disease: an updated classification system.
AB  - The study included 736 probands with ulcer disease and 110 healthy subjects as
      well as all their relatives up to a third-degree of relation (n = 21889). All
      subjects underwent a thorough genealogical analysis, blood group, PTC and
      dermatoglyphic studies were performed on the whole contingent. Using extensive
      genealogical, genetico-mathematical and multifactorial analysis we studied the
      manifestations of anticipation, the influence of hereditary predisposition on
      gastric secretion and acidity under conditions of maximum pentagastrin
      stimulation as well as the disease inheritance pattern. The results of our
      comprehensive studies suggest that type I gastric ulcer according to H. Johnson,
      unlike type II and type III, is not genetically determined. On the other hand,
      type II and type III gastric ulcer do not differ substantially from duodenal
      ulcer and should therefore be categorised as belonging to this form of the
      disease. On this basis we propose a new classification system which accepts the
      existence of two ulcer diseases: gastric ulcer disease, and ulcer disease of the
      pyloroduodenal region.

PMID- 8979453
TI  - Influence of the type of family predisposition on the age of ulcer disease onset.
AB  - 736 probands with endoscopically and/or roentgenologically proven ulcer disease
      of the stomach and duodenum were studied. Of these 429 were with hereditary
      predisposition to the disease (including in the study all their third-degree
      relatives). Our findings suggest that the age of disease onset is markedly
      dependent on the type of familial predisposition. It occurs the earliest and
      relatively the most frequently in probands with two affected parents (familial
      predisposition type III). The peak frequency of the disease for non-predisposed
      subjects is between 30 and 39 years of age while in subjects with familial
      predisposition of the first type (two healthy but genetically predisposed
      parents) the II-A type (a sick father) and the II-B type (a sick mother) it
      occurs a decade earlier. Type III familial predisposition causes the disease to
      affect the probands even earlier by another decade so half of all the probands of
      this type of familial predisposition are affected by the disease by the age of
      19. The different types of familial predisposition to gastric ulcer (types II and
      III) and duodenal ulcer reflect the hereditary ulcerogenic load received by the
      offspring. All other conditions being equal, the greater it is the earlier the
      disease occurs.

PMID- 8979454
TI  - A new index for assessing arterial oxygen profile in patients with respiratory
      failure.
AB  - A new index, termed 'useful ratio' of the blood oxygen binding curve, was derived
      on the basis of the characteristic features of hemoglobin oxygen (transported,
      reserve and practically non-usable hemoglobin oxygen). The index gives the ratio
      of the useful to the predicted total hemoglobin oxygen of patients. It is
      functionally related to the fraction of the measured transpulmonary shunt
      (FShunt), shows high correlation with the blood gases (pO2 and pCO2), correlates
      moderately with the hydrogen exponent, poorly with the oxygen affinity (P50) and
      the metabolic acid-base parameters (cHCO3), and does not show to be essentially
      related to the total oxygen concentration (cO2) and PO2(x), the new index
      proposed in the Oxygen Status Algorithm. Diagnostically, this index has much the
      same value as that of the calculated shunt (FShunt); it can be used only in
      diagnosing the conditions of hyperoxia, normoxia, and hypoxia and excludes
      detecting those of hyperoxemia, normoxemia, and hypoxemia. Simultaneous
      assessment of this index together with pO2(x) enhances further the diagnostics of
      respiratory insufficiency providing the necessary information about the mechanism
      of respiratory decompensation that is of importance for an efficacious treatment.

PMID- 8979455
TI  - Computer classification of screening study of risk factor for ischemic heart
      disease in 20-60 year old subjects.
AB  - Screening was performed of 2162 industrial workers aged 20-60 years for risk
      factors for ischemic heart disease. The computer classification of all subjects
      investigated gave the following distribution: healthy subjects without any risk
      factors-21 men (1.59%), 26 women (2.61%); healthy subjects with risk factors-609
      men (46.14%) and 469 women (47.09%); subjects with borderline arterial
      hypertension without other risk factors-13 men (0.98%) and 10 women (1.0%);
      subjects with arterial hypertension concomitant with other risk factors-295
      (22.35%) and 224 women (22.49%). There were no subjects with ischemic heart
      disease without the major and secondary risk factors. The subjects with both risk
      factors and ischemic heart disease were 154 men (10.01%) and 216 women (18.0%).
      ECG changes (by Minnesota code) were found in 339 male (25.0%) and 178 female
      subjects (14.8%).

PMID- 8979456
TI  - Increase of aerobic capacity by submaximal training and high-fat diets.
AB  - Forty male Long-Evans rats were used in an 8-week experiment designed to study
      the possibilities of using fats to increase aerobic work capacity and to
      elucidate the mechanisms of aerobic adaptation. The animals were divided into
      four groups: group SD comprised control rats kept on a standard diet and
      sedentary regimen; group HFD were given a high-fat diet (78 en.% of fats) and no
      training; group SDT consumed standard diet and were trained submaximally; group
      HFDT was on a high-fat diet and submaximal training. Submaximal running endurance
      (SRE) and maximum oxygen uptake (VO2max) tests were carried out in all groups. To
      clarify some of the mechanisms of aerobic adaptation we measured the glycogen
      content in m. gastrocnemius and the activity of key enzymes for the carbohydrate
      and fat metabolism, citrate synthase (CS), 3-hydroxiacetyl-CoA-dehydrogenase (3
      HAD), and carnitine palmitoyl transferase (CPT) in muscle homogenates. It was
      found that a high-fat diet (HFD) improved the submaximal running endurance and if
      combined with submaximal training increased its effect several-fold. HFD
      increased the maximum oxygen uptake, training made it even greater, but the
      effect on VO2max the greatest when the two were used in combination. CS activity
      in m. soleus in HFD-fed rats was 23% greater than that in group SD, while 3-HAD
      activity was 27% higher than that in group SD. CPT activity in group HFDT was
      twice as great as that of the control group. Under the influence of HFD the
      muscle fibres underwent a shift of the energy substrate from carbohydrates to
      fats which was proved by the economical muscle glycogen depletion during physical
      exercise.

PMID- 8979457
TI  - Ultrastructural study of hemangiomas in children.
AB  - An electron microscopic study was carried out of different kinds of hemangiomas
      (capillary, cavernous and combined) in 18 children at the age of two months up to
      one year. Centers of differently expressed proliferation both of the endothelial
      cells and pericytes were found. The proliferation was most distinctly expressed
      in the capillary and cavernous hemangiomas. At the later stages, regressive and
      involutive changes, presented better in the capillary hemangiomas, were observed.
      The authors consider that hemangiomas, irrespective of their active cell growth,
      are tumours with a good prognosis.

PMID- 8979458
TI  - Histochemical study on hemangiomas in childhood.
AB  - The study was carried out on a material obtained by a biopsy from 18 children
      having different types of hemangiomas (capillary, cavernous and combined).
      Histochemical reactions were applied for the following enzymes:
      Succenatedehydrogenase (SDH), lactatdehydrogenase (LDH), cytochromoxidase, acid
      phosphatase, alkaline phosphatase and paraspecific esterases. Differently reduced
      activity of the succenatedehydrogenase and the cytochromoxidase in the
      endothelial cells and the pericytes was established. A reduced enzyme activity
      was observed also in a large part of the cases of acid phosphatase. The activity
      of the alkaline phosphatase and paraspecific esterases was greatly increased.
      Based on their observations the authors relate the hemangiomas to the tumour
      formations with a good prognosis.

PMID- 8979459
TI  - Experimental data on the effect of nitrates entering the organism with the
      drinking water.
AB  - A six-months continuous experiment was carried out on 48 viripotent white female
      rats, line "Vistar", divided into one control and three experimental groups of 12
      rats each. The experimental groups received drinking water containing nitrates
      50, 100 and 500 mg/dm3, respectively and the control group-7.0 +/- 0.03 mg/dm3.
      All animals were fed with a standard vivarium food containing 22.0 +/- 0.1 mg/kg
      nitrates. Upon expiry of the test period the animals were killed. Blood
      parameters and some internal organs were studied by macro- and microscopy.
      Microscopic changes in the thyroid gland, liver, kidneys, small and intestines,
      stomach of the test animals were established. The results of the blood analysis
      showed statistically significant deviations in haemoglobin values and the
      differential blood count as well as in some serum parameters.

PMID- 8979460
TI  - Novel mitochondrial DNA insertion polymorphism and its usefulness for human
      population studies.
AB  - The frequency of a polymorphic mitochondrial DNA insertion into the nuclear
      genome was determined for 870 individuals from a geographically diverse set of 20
      populations. The mtDNA insertion frequency varies significantly among
      populations, having a large GST value (0.178) and high heterozygosity values
      within populations. The clinal pattern of increasing frequency of the insertion
      from Africans through Europeans and Asians to native Americans is striking. The
      polymorphism is a new example of insertion-deletion polymorphisms and is a
      valuable marker for human population and evolutionary studies.

PMID- 8979463
TI  - Genetic variation in the population of Ibiza (Spain): genetic structure,
      geography, and language.
AB  - A sample of 203 individuals from Ibiza (Balearic Islands, Spain) were tested for
      blood group and serum protein genetic variation and compared with other circum
      Mediterranean populations. Allele frequencies were calculated for the following
      blood group and serum systems: ABO, Rh, MNSs, P, Lewis, Duffy, Kell, ORM, GC, TF,
      PI, and HP. The allele frequencies from Ibiza were compared with those from other
      Balearic Islands (Majorca and Minorca) and with related European and North
      African groups using an assortment of analytical methods (genetic distances, R
      matrix analysis, and Mantel tests). R matrix analysis revealed that Ibiza is
      genetically different from the other Balearic populations and, because of gene
      flow from Spain, clusters with European groups. The level of genetic
      microdifferentiation of the Mediterranean populations, measured by RST (average
      of the R matrix diagonal elements, rii), is 0.028. An examination of the
      relationship between genetic, geographic, and linguistic distances by Mantel
      tests revealed that genetic distances are significantly correlated with
      linguistic distances, whereas the genetic distances are not significantly
      correlated with geographic distances. The plot of mean per locus heterozygosity
      versus the genetic distance from the centroid of distribution revealed that all
      three Balearic Islands have experienced considerable gene flow but that Ibiza has
      been most affected by the action of stochastic processes.

PMID- 8979462
TI  - Historical population movements in Europe influence genetic relationships in
      modern samples.
AB  - We have newly constructed an ethnohistorical database consisting of 3460 records
      of ethnic locations and movements in Europe since 2200 B.C. Using this database,
      we computed vectors of proportions that peoples speaking various language
      families contributed to the gene pools of 2216 1 degree x 1 degree land-based
      quadrats of Europe. From these vectors we computed ethnohistorical distances as
      arc distances between all pairs of quadrats. We used these distances as
      predictors of genetic distances, which we calculated independently from 26
      genetic systems. We find significant partial correlations between ethnohistorical
      and genetic distances when geographic distance, a common causative factor, is
      held constant. Ethnohistorical distances explain a significant amount of the
      genetic variation observed in modern populations. These results are highly robust
      to simulated errors in and omissions from the ethnohistorical database.
      Randomization tests show that the historical sequence of the movements does not
      affect estimates of the ethnohistory-genetics correlation, but the geographic
      locations of movements do. We track the development of the ethnohistory-genetics
      correlation through time and show it to be gradual and cumulative over the past
      4200 years.

PMID- 8979464
TI  - Genetic structure of populations in western Tyrol.
AB  - ABO, MNSs, and RH blood groups of 920 indigenous inhabitants of two western
      Austrian mountain valleys were identified, and frequencies of 17 genes and
      haplotypes were estimated. FST coefficients between the six larger villages were
      computed and served as the basis for dendrograms by average linkage, a principal
      components analysis, and a nonlinear map that includes European groups in
      addition to the Tyrolean population. The genetic distances between the Tyrolean
      villages are somewhat larger than those among Appenine villages. The two most
      accessible villages are closest to the neighboring European groups, whereas the
      more remote villages appear more distant to these. Nevertheless, the gene
      frequencies are typical of central European populations.

PMID- 8979465
TI  - Microevolution and genetic affinities among six Amerindian tribes of lower
      Central America: comparative genetic study of serum proteins.
AB  - We evaluate the pattern of genetic variation among native Mesoamerican
      Amerindians by the construction of a gene frequency map that reflects the past
      action of evolutionary forces. The analysis is based on the theory that genes of
      modern human populations carry the encoded history even of humans' remote past
      and their early wanderings around the globe. We examined the serum proteins TF,
      PI, F13B and AHSG on 491 samples of 6 Mesoamerican Amerindian tribes (Guaymi,
      Bribri, Cabecar, Teribe, Guatuso, and Huetar) and 2 tribal mixed samples (Teribe
      x Guaymi and Bribri x Cabecar). We find a distinct genetic pattern in the
      examined tribes that clearly separates the Mesoamerican Amerindians from other
      living Amerindian groups. The proteins, TF, PI, and AHSG proved to be especially
      rich in special genetically fixed variants and polymorphisms, and F13B proved to
      be a powerful genetic marker to distinguish human groups. Using Nei's distance D
      and Mahalanobis's D2, we compared the polymorphisms and allele frequencies at the
      four serum protein loci to discern degrees of similarity between the samples.
      These data are presented in the dendrograms computed by average linkage cluster
      analyses and in two kinds of unrooted phylogenetic trees, neighbor-joining trees
      and split decompositions. Estimations are made on Hardy-Weinberg equilibrium and
      on genetic diversity and average heterozygosity index.

PMID- 8979466
TI  - Salivary testosterone levels among Tamang and Kami males of central Nepal.
AB  - Salivary testosterone levels are reported for 65 Nepalese males between the ages
      of 15 and 48 years who were drawn from 2 different ethnic populations (Tamang and
      Kami) from the central highlands of Nepal. Subjects collected morning and evening
      saliva samples on five consecutive days in two contrasting seasons, the winter
      dry season and the summer monsoon season. Anthropometric indexes of acute and
      chronic nutritional status were also measured. Morning and evening salivary
      testosterone levels in the winter averaged 233 +/- 14 (SE) pmol/L and 166 +/- 8
      pmol/L, respectively, for the Tamang and 249 +/- 14 pmol/L and 163 +/- 13 pmol/L,
      respectively, for the Kami. In the summer the corresponding values were 219 +/-
      12 pmol/L and 156 +/- 8 pmol/L for the Tamang and 249 +/- 19 pmol/L and 147 +/-
      12 pmol/L for the Kami. These levels are significantly lower than those reported
      for Western populations and close to those reported for other non-Western
      populations. The magnitude of diurnal variation in salivary testosterone levels
      and the absence of significant age variation are also comparable with
      observations made on other populations. Weak relationships were observed between
      testosterone levels and indexes of acute and chronic nutritional status in the
      winter only. The absence of pronounced variation in salivary testosterone levels
      between populations and the absence of strong associations between salivary
      testosterone levels and indexes of acute and chronic nutritional status contrast
      with the prominent ecological and interpopulation variation reported for salivary
      progesterone levels in women. Male gonadal function seems less sensitive to
      moderate energetic stress than female gonadal function, probably reflecting the
      fact that energy availability is less crucial to male reproductive success than
      to female reproductive success. Variation in testosterone level associated with
      chronic energetic stress may be an adaptive somatic response to avoid the
      maintenance costs of a large active metabolic mass with little direct impact on
      male fecundity.

PMID- 8979467
TI  - Timing of menopause in relation to body size and weight change.
AB  - Age at menopause was examined in relation to weight and body mass index (BMI)
      (kg/m2) in 105 women,. age 41 years and older, who recalled the date of their
      last menstrual period to be at least 12 months before the interview. Mean
      recalled age at menopause was 49.3 years (SD 4.8); median age at menopause, by
      probit analysis, was 49.96. Age at menopause was negatively correlated with
      weight (r = -0.252, p < 0.05) and BMI (r = -0.204, p < 0.05) at interview;
      however, weight at time of interview is not necessarily an accurate indicator of
      weight at the time of menopause. Among women who did not report a gain or loss of
      50 pounds across adulthood (n = 59) there was no significant correlation between
      weight or BMI and age at menopause. Age at menopause was earlier among women who
      reported weight losses of 50 or more pounds across adulthood (p < 0.01). In
      addition, age at menopause was earlier among women who reported weight gains of
      100 or more pounds, although this difference was not significant at p < 0.05.
      Further attention should be given to weight change in relation to the timing of
      menopause.

PMID- 8979468
TI  - Epidemiological observations on cancer of the oesophagus--a review of Indian
      studies.
AB  - This is an epidemiological review on cancer of the oesophagus. In this attempt,
      all aspects of epidemiological factors based on national and international
      studies on oesophageal cancer have been brought out. The problem of this cancer
      in Indian context has been documented. The association of tobacco and alcohol
      habits with oesophageal cancer has been confirmed from the studies conducted in
      India. There is an urgent need to educate the common people about the harmful
      effect of these two habits and governments and voluntary organisation should take
      effective steps for its prevention.

PMID- 8979469
TI  - Prognostic value of argyrophylic nucleolar organiser regions (AgNORs) in breast
      lesions.
AB  - A total of 200 breast tissues which included 5 normals, 55 benign and 140
      malignant lesions were stained for Argyrophilic Nucleolar Organiser Regions
      (AGNORs). A comparison of the AGNOR values with histologic variables, viz., tumor
      type, size nuclear grade, desmoplasia, elastosis, lymph node metastasis and
      Oestrogen and Progesterone Receptor (ER/PR) status was carried out in malignant
      lesions. AGNOR values could sharply distinguish benign from malignant lesions.
      Among the malignant lesions, an attempt to determine the value of AGNOR count in
      prognostication was made. AGNOR counts correlated with tumor size, mitoses and
      desmoplasia. ER/PgR negative tumors showed a tendency for high NOR counts, but
      lymph node metastasis, which is considered one of the most reliable prognostic
      indicators, did not concur with AGNOR counts in our study. These results indicate
      that AGNOR counts can not be used as a sole independent marker in breast cancer
      prognostication.

PMID- 8979470
TI  - Basaloid-squamous carcinoma. A distinct histopathological entity.
AB  - Basaloid Squamous Carcinoma (BSC) is an uncommon aggressive neoplasm occurring in
      the upper aerodigestive tract. Lung as a primary site has only recently been
      reported. A combination of microscopic features is required to make a diagnosis
      and to differentiate it from other more common malignancies in these sites. Three
      cases of BSC including one in the lung are reported. There are no prior published
      reports of this neoplasms in Indian literature. The study highlights the typical
      microscopic features and the diagnostic difficulties which may be encountered.

PMID- 8979471
TI  - Primary carcinoma of the fallopian tube. A clinicopathologic study.
AB  - Five cases of primary fallopian tube carcinoma were located in 30 years
      retrospective study (1965-1994) from the Department of Pathology, Kasturba
      Medical College, Mangalore, Karnataka. Abnormal vaginal bleeding was the
      presenting symptom in all the cases. Pelvic mass was palpable in four cases. The
      diagnosis was not suspected preoperatively in any case. All patients underwent
      surgical treatment. Laparotomy revealed the presence of a macroscopic growth in
      the fallopian tube which was confirmed to be adenocarcinoma histopathologically
      in all the cases. In three cases follow-up is available. Only one patient
      received postoperative radiotherapy and chemotherapy.

PMID- 8979474
TI  - Carcinoma penis in a young boy. A case report.
AB  - Carcinoma of the penis below the age of fifteen years is a rarity. A 14 year old
      boy presenting with advanced carcinoma penis with bilateral fungating inguinal
      lymphadenopathy is the subject of this case report.

PMID- 8979472
TI  - Central nervous system ganglioglioma. A clinicopathologic study.
AB  - Gangliogliomas are one of the uncommon tumours of central nervous system. Since
      these tumours have been associated with an indolent clinical course and benign
      biological behaviour, it is essential to make an accurate histopathological
      diagnosis of ganglioglioma. In this study the salient clinical and
      histopathological features in six patients with intracranial ganglioglioma are
      described.

PMID- 8979475
TI  - Choriocarcinoma of the ovary in a post-menopausal woman.
AB  - A case of a Choriocarcinoma of the Ovary has been reported in a 50 year old post
      menopausal woman. At laparotomy, the lesion was seen as a large necrotic ovarian
      mass. The problems of distinguishing Gestational from Non-gestational ovarian
      choriocarcinoma are discussed. Cytogenetic studies are indicated to investigate
      potential reasons for the difference in prognosis.

PMID- 8979473
TI  - Primary central nervous system lymphoma a report of nine cases.
AB  - Primary Central Nervous System Lymphoma (PCNSL) is a rare neoplasm of B cell
      origin and constitute less than 1% of Non-Hodgkin's lymphoma (NHL). Histology is
      mainly of high grade and intermediate type. Although NHL is known to be highly
      sensitive to both irradiation and cytotoxic drugs, being a curable malignancy,
      the therapeutic results remain disappointing. Clinical observations on nine cases
      of PCNSL seen in one of the major cancer centres in India is presented in this
      paper. Radiotherapy combined with Chemotherapy although yielded encouraging
      initial response in these patients, the long term response was unsatisfactory
      with median survival for these patients being only 19 months. This warrants an
      alternative therapeutic approach to improve the dismal prognosis of PCNSL.

PMID- 8979476
TI  - Immunotoxicity of pesticides: perspectives and trends.
AB  - In recent years, great concern has been expressed about genotoxic potential of
      pesticide chemicals. These toxic chemicals have become an integral part of the
      ecosystem and the human health effects of these agents are yet to be
      satisfactorily defined. The objectives of this review is to examine the sources
      of information available; evaluation of experimental protocols employed for
      assessment of immunological effects; and to study specific cellular and molecular
      locus which could be responsible for impaired immune responsiveness. It is
      emphasized that threshold level for the pesticide effect below which no effect
      would be seen, depends on the animal species, the method of testing for immune
      responses and type of antigen used. A comparative assessment of immune responses
      using different antigens is, therefore, an important aspect of pesticide
      immunotoxicity. In view of widespread use, distribution and stability of some of
      these compounds in the environment, pesticide exposure may play a greater role in
      suspected fragile immune system, and may result in altered disease
      susceptibility. An understanding of these risks depends, to a great extent, upon
      cellular and molecular events underlying pesticide-induced immune alterations in
      experimental animals. It is, therefore, proposed that pesticide chemicals may
      influence humoral immunity while having no detectable effect on cell-mediated
      immunity (CMI); immune dysfunction is related to dose and duration of pesticide
      exposure; a single assay of immune function may not be appropriate to detect
      pesticide-induced immune dysfunction; since many immune responses are genetically
      controlled, alterations in responsiveness to one challenge in a given animal
      model may not hold true in second one; although it has been established that
      pesticide chemicals can alter immune function, the mechanisms of action have yet
      to be determined. This paper also reviews the effects of pesticide on lymphocyte
      function and suggests that lymphocyte dysfunction may be an integral part of
      pesticide-induced immunosuppression and presents an approach which may serve to
      delineate the possible mechanisms of action. It is quite clear that pesticide
      induced immunomodulation endangers humans and animals. This hazard should,
      therefore, not to be underestimated in evaluation of toxicity of these chemicals.
      However, additional research is needed in basic mechanism of immunotoxicity and
      identification of susceptibility factors which predispose to these reactions.

PMID- 8979477
TI  - Comparative evaluation of serological tests for diagnosis of visceral
      leishmaniasis.
AB  - Sensitivity and specificity of the direct agglutination (DAT) and indirect
      immunofluorescent test (IFT) have been compared with indirect immunoperoxidase
      assay (IPA) for the serodiagnosis of visceral leishmaniasis. IPA and DAT were
      found to be more sensitive and specific than IFT. Indirect immunoperoxidase test
      was found to be better than DAT as preparation of antigen is easy. Less amount of
      antigen is required, storage of antigen in slide form is more convenient and
      shelf life is longer. It is easier to read and interpret immunoperoxidase with
      the help of ordinary light microscope and chances of false positive and false
      negatives are negligible.

PMID- 8979478
TI  - Effect of plumbagin on gonadotrophic cycle of the housefly, Musca domestica L.
AB  - Topical treatment of the phytochemical plumbagin in doses ranging 0.005-5
      micrograms prevented oocyte development and affected fecundity and fertility in
      M. domestica. The treatment to wandering larvae was less effective as the
      compound could only effect the fertility to a significant level whereas the
      fecundity was not significantly reduced. The effect of the compound was more
      pronounced in adult treatments where both fecundity and fertility reduced
      drastically. The compound also effected the oocyte maturation as it arrested the
      development of vitellogenic oocyte at stage six. As the juvenile hormone analogue
      methoprene and moulting hormone 20-hydroxyecdysone or the mixture of these
      hormones could not restore the development of the oocyte in ovaries of plumbagin
      treated flies, it is concluded that the compound does not effect the female
      houseflies through hormonal pathways, instead in all probability it acts like a
      cytotoxic compound.

PMID- 8979479
TI  - Anti-ulcerogenic activity of GABA and GABA mimetic agents in rats.
AB  - To elucidate the involvement of peripheral gamma- aminobutyric acid (GABA) and
      some GABA-mimetic agents in different models of gastric and duodenal ulcerations
      in rats and guinea pigs, effects of GABA, baclofen (GABAB agonist), diazepam,
      gamma-butyrolactone (GABA receptor agonist), sodium valproate, isoniazid (GABA-T
      inhibitor) and glycine (an inhibitory neurotransmitter), given po or ip were
      studied. All the drugs significantly reduced the ulcer index, incidence and
      number of ulcer in various models of gastric ulcers except glycine which failed
      to protect in reserpine-induced ulcers in rats. None of the drugs, except
      diazepam, had any protective effect on histamine-induced gastric ulcers in guinea
      pigs. Similarly, no protection was observed by any drug against cysteamine
      induced duodenal ulcers in rats, while sodium valproate, isoniazid and glycine
      significantly decreased number of ulcers against histamine-induced duodenal ulcer
      in guinea pigs. The results suggest that GABA and GABA-mimetic agents, and
      glycine, an inhibitory neurotransmitter, afforded protection against some
      experimental models of peptic ulcer in rats. The effects appear to be due to
      their inhibitory effect on mucosal defensive factors.

PMID- 8979480
TI  - Discrimination of transport systems of L-tyrosine in mouse mammary gland:
      characterization of system T.
AB  - On the basis of inhibition analysis, tyrosine uptake in mouse mammary gland was
      found to be mediated by Na(+)-dependent and Na(+)-independent systems. Na(+)
      dependent system was insensitive to 2-(methylamino) isobutyric acid (MeAIB), with
      an apparent Km of 1.67 mM and maximal velocity 74.5 nmol.g-1 cell. min-1.
      Competition experiments showed the presence of two distinct Na(+)-independent
      components of tyrosine uptake. One component was sensitive to 2-aminobicyclo
      (2,2,1) heptane-2-carboxylic acid (BCH) and was similar to the system L, with an
      apparent Km of 0.23 mM and maximum velocity of 31 nmol.g-1 cell.min-1. Second
      component was BCH-insensitive but tryptophan-sensitive, with an apparent Km of
      15.75 mM and Vmax of 157.5 nmol.g-1cell.min-1. BCH-insensitive, tryptophan
      sensitive system was a low affinity system. It approached steady state slowly and
      was more sensitive, relative to the system L, to n-ethylmaleimide inhibition.
      Tyrosine uptake through this system did not respond to trans-stimulation, whereas
      system L mediated uptake responded considerably. BCH-insensitive, tryptophan
      sensitive component of Na(+)-independent tyrosine uptake is attributed to the
      system T, previously described only in human red blood cells and rat liver cells.

PMID- 8979481
TI  - Influence of melatonin on blood morphology in male albino mice.
AB  - Influence of melatonin on diurnal changes in hematological profiles was examined
      in male albino mice, at six hourly interval. Melatonin treatment either once
      daily (25 micrograms at 1700 hrs) or twice daily (25 micrograms at 0900 and 1700
      hrs) for two weeks resulted in an alternation in the RBC rhythm. Generally the
      effect was suppressive though at some times the counts were marginally increased.
      Total WBC counts were increased and there was apparently a change in their rhythm
      too. Interestingly the differential WBC counts exhibited different patterns in,
      once and twice daily melatonin-treated mice. Melatonin given once daily
      predominantly stimulated the absolute lymphocyte count whereas the twice daily
      regimen predominantly stimulated the neutrophil count. This perhaps is related to
      the varied exposures of the animals to melatonin in the two experimental setups.
      Erythrocyte indices like mean cell volume, mean cell hemolglobin and mean cell
      hemoglobin concentration in both the experiments correlated with hemoglobin and
      hematocrit values. It may be concluded that melatonin has a modulatory role in
      hemopoiesis and its rhythms. The stimulatory effect of melatonin on WBC supports
      its purported immunopotentiating action.

PMID- 8979483
TI  - Duration of cell cycle, onset of S phase and induced mitotic synchronisation in
      seeds of opium poppy, Papaver somniferum L.
AB  - Duration of mitotic cell cycle and its component phases in root-tip meristem of
      P. somniferum was determined following autoradiographic detection of mitotic
      rythms during the traverse of cell cycle. The mitotic cycle time thus estimated
      was found to be 12.6h of which the distribution of component phases was G1 = 1.75
      h, S = 6.3 h, G2 = 3.75 h and division phase (M) = 0.8 h. Dry seeds were
      metabolically activated by soaking in water to show that the first batch amongst
      the asynchronous population of cells in the seeds enters into S phase after 18 h
      of such soaking at 16 degrees C. Mitotic synchrony to the tune of 80% could be
      realised when such presoaked seeds were administered 5 mMole hydroxyurea for 20 h
      at 16 degrees C.

PMID- 8979482
TI  - Toxicity and antitumor activity of niosomal bleomycin in tumor bearing mice.
AB  - Niosomal encapsulation of bleomycin enhanced the antitumor activity against
      Ehrilich ascites and sarcoma-180 models. The niosomal/free drug mean survival
      time values of 1.28 was achieved in Ehrlich ascites infected animals. Niosomal
      bleomycin considerably increased the 40 days survival rate in mice. Tumor volume
      doubling time of S-180 tumor was also increased significantly in niosomal treated
      animals. Histopathological studies of lung and jejunum of Niosomal bleomycin
      treated mice, confirmed the less toxic potential of encapsulated bleomycin. The
      suppression of peripheral and bone marrow WBC counts upon niosomal bleomycin
      treatment was not substantial.

PMID- 8979484
TI  - Age-related decline in multiple unit action potentials of cerebral cortex
      correlates with the number of lipofuscin-containing neurons.
AB  - The present study examined whether there is any obvious correlation between the
      density of lipofuscin-containing neurons and the spontaneous neuronal action
      potentials (Multiple Unit Activity, MUA) in the parietal cortex of the aging rat
      brain. The results showed that MUA counts were decreased with age while the
      number of lipofuscin-containing neurons was increased. The cortex with the
      highest percentage of lipofuscin-containing neurons had the lowest MUA counts
      while the cortex with the lowest percentage of lipofuscin-containing neurons had
      the highest MUA counts. The inverse correlation between MUA and lipofuscin
      containing neuron number was also evident when the population of the lipofuscin
      containing neurons was pharmacologically altered in vivo by the administration of
      anti-lipofuscin drug centrophenoxine. The inverse relationship between MUA and
      the lipofuscin-containing neuron numbers is consistent with: (i) the correlations
      of MUA with age-related changes in lipid peroxidation and biochemically measured
      lipofuscin concentration, and (ii) the oxidative stress-induced impairments of
      neuronal electrophysiology.

PMID- 8979485
TI  - Changes in tubular membrane glycosylation in diabetic, insulin and thyroxin
      treated rat kidneys.
AB  - The effect of insulin, thyroxine and alloxan induced diabetes has been studied on
      brush border membrane glycosylation in rat kidneys. Expressed on dry weight
      basis, the membrane protein was elevated in insulin, thyroxine and diabetic
      membranes compared to the control group. Sialic acid content of the membranes was
      significantly reduced in insulin and thyroxine injected animals whereas fucose
      level was unaffected under these conditions. Brush border fucose content was
      significantly reduced in diabetic animals but sialic acid content was unaffected.
      Membrane hexose and hexosamines levels were unaltered by hormone treatments, but
      in diabetic rats hexosamine level was significantly reduced. The binding of
      radiolabelled UEA, WGA, PNA to purified brush borders corroborated changes in
      membrane saccharides. These findings suggest the role of hormones in membrane
      glycosylation of rat kidney tubules.

PMID- 8979486
TI  - Ca(2+)-transport across brush border and basal surfaces of human term [correction
      of terms] placenta.
AB  - Brush border microvillous (BBM) and basal cell membranes (BCM) were isolated from
      syncytiotrophoblast of human term placenta by homogenization, sonication,
      prolonged stirring and differential centrifugation. Uptake of 45Ca(2+)-CaCl2 in
      membrane vesicles in morpholino propane sulphonic acid (MOPS) buffer was studied
      up to 60 min. Maximum uptake of the radioisotope was recorded at 10 and 15 min of
      incubation of the BBM and BCM, respectively. Radioisotopic uptake was also
      dependent on the Ca(2+)-concentration, linear up to 3 mu mole and then assuming
      hyperbolic substrate saturation kinetics. The Lineweaver-Burk transformation of
      the data gave Kt value for BBM and BCM, 0.85 and 1.08 microM, respectively while
      the Vmax of uptake (Jmax) in the same were 105.26 and 188.68 pmole Ca2+/microgram
      protein/20 min. Ca(2+)-Uptake in placental BBM and BCM vesicles was inhibited by
      two Ca(2+)-channel blockers, nifedipine and verapamil to as much as 50% while
      Ca(2+)-ionophore A23187 enhanced the uptake process significantly.

PMID- 8979487
TI  - Crop improvement and disease suppression by a Bacillus spp. SR2 from pea nut
      rhizosphere.
AB  - An antibiotic producing Bacillus strain SR2, isolated from pea nut rhizosphere,
      showed in vitro antibiosis against many known plant pathogens. Seed bacterization
      with this strain showed an enhancement in seed germination, shoot height, root
      length, fresh and dry weights in four crop plants. A multiple drug resistant
      strain, SR2+, used to monitor root colonization confirmed the root colonization
      by the organism. Seed bacterization, reduced the number of chick pea wilted
      plants in wilt-sick soil, making the organism a potential bio-control agent
      against chick pea wilt.

PMID- 8979488
TI  - Myosin light chains in regenerating graft in chick gastrocnemii.
AB  - Myosin light chains in normal and minced autografted chick gastrocnemii have been
      studied by disc gel electrophoresis during 70 days postgrafting period. As a
      result of induced mechanical trauma, the quantitative relationships between
      myosin light chain fractions are disturbed affecting the muscle functions.

PMID- 8979489
TI  - Regeneration of encapsulated protocorms of Phaius tankervilliae stored at low
      temperature.
AB  - Embryos (80 days old) developed after selfing P. tankervilliae were cultured on
      Nitsch medium for protocorm development. Protocorms (70 days old) thus developed
      were encapsulated with alginate matrix. Ninety six per cent of freshly prepared
      encapsulated protocorms differentiated into shoots and roots when cultured on
      Nitsch medium. Storage of encapsulated protocorms in sealed petri plates or by
      embedding in liquid paraffin at 4 degrees C showed no reduction in their
      regeneration frequency up to 120 days when cultured on Nitsch medium. However,
      90% of encapsulated protocorms stored at room temperature in empty petri plates
      differentiated within 35-40 days. Regeneration frequency of encapsulated
      protocorms was drastically reduced when stored in liquid paraffin at room
      temperature.

PMID- 8979490
TI  - Rooting and establishment of in vitro grown shoot tip explants of chickpea (Cicer
      arietinum L.).
AB  - Shoot tip explants of 5.chickpea varieties were evaluated for efficiency of
      rooting using MS basal medium (1/4, 1/2 and full strength). Maximum rooting was
      observed in 3 varieties when cultured in MS medium with 1/4 strength. Plantlets
      thus developed, were further cultured in Hoagland solution (1/4 strength) for 15
      20 days which enhanced root number and root length. Such plantlets established
      well in vermiculite/soil.

PMID- 8979492
TI  - Microtubers from somatic embryos of Bunium persicum.
AB  - Improvement in induction and growth of microtubers was related to macro and micro
      constituents of MS-medium, kinetin and sucrose levels. MS-medium at half strength
      constituents induced more conversion of somatic embryos (75%) with marginally
      longer and more tubering shoots (75%). However, tuber size was one third of full
      strength medium grown tubers. Addition of various concentrations of kinetin
      revealed a dose dependent stimulatory relationship in tuber formation showing
      enhanced tuber formation and their growth at 1 x 10(-8) M kinetin level. All
      plantlets produced tubers of 32.5 mg average weight. Plant conversion and shoot
      growth was maximum at 30 g/L of sucrose concentration and tuber weight increased
      approximately five times when sucrose level was raised to 60 g/L. Tubering
      explants also increased from 2 to 90%.

PMID- 8979491
TI  - Electron microscopic characteristics of actinomycetic agents having aetiological
      association with human leprosy and epizootic ulcerative syndrome of fish.
AB  - The transmission electron microscopic (TEM) studies of the human leprosy derived
      chemoautotrophic nocardio-form (CAN) bacteria and EUS derived CAN bacteria showed
      presence of double contoured cell-walls consisting of an electron transparent and
      a dense layer. The fibrillar structures on the surface of these CAN bacterial
      cells also suggested their similarity to the human tissue derived Mycobacterium
      leprae cells. These EM studies further revealed mycelial and coccoid bodies in
      all these bacteria as was observed originally.

PMID- 8979493
TI  - Development of indicators for cephamycin bioassay.
AB  - Several species of bacteria have been tested, for their sensitivity to cephamycin
      C and other beta-lactam antibiotics with a view to develop an indicator system
      for identification and quantitation of cephamycin. During the study, a mutant
      derived from E. coli K 802, exhibited a 10-fold increased sensitivity to
      cephamycin C than E. coli ESS (reference strain)1,2 and was designated as
      supersensitive E. coli K 8025. Another interesting feature observed during the
      investigation was that a strain of Serratia, showed a high degree of resistance
      to penicillins and cephalosporins however, it was sensitive to cephamycin and its
      derivative. It has been suggested that E. coli K 8025 and Serratia would serve as
      good indicator organisms for detection and quantitation of cephamycin.

PMID- 8979494
TI  - In vitro susceptibility of goat mononuclear cells to bluetongue virus.
AB  - Goat peripheral blood mononuclear cells were cultured and their susceptibility to
      bluetongue virus (BTV) serotype 1 was tested. A small number of adherent and non
      adherent cells were found positive for BTV antigens by immunoperoxidase and
      immunofluorescence tests. Both adherent and non-adherent cells supported limited
      level of viral replication as evidenced by low titre in the biological assay,
      thus indicating their susceptibility.

PMID- 8979495
TI  - Copper effect on photosynthesis and transpiration in safflower.
AB  - The young leaves of safflower plants subjected to deficient supply of copper
      (0.00063 mg Cu L-1) developed visible symptoms of Cu deficiency and showed a
      decrease in chlorophyll concentration, Hill activity, net photosynthesis and
      transpiration. On giving normal supply of Cu (0.063 mg Cu L-1), these changes
      were partially reversed.

PMID- 8979496
TI  - Pharmacologic quantitation.
AB  - Either in vivo or in vitro quantitatives comparisons of drugs based on the dose
      response relations were known for a long time. For therapeutically targeted
      molecular structure activity studies, agonists are simply compared on the basis
      of concentrations eliciting half-maximum response (EC50) and per cent maximum
      response elicited by drugs in the given system. For partial agonists the receptor
      affinity determined as the dissociation constant (KA) in homogenates corresponds
      to that in the organ system. However, due to the presence of spare receptors the
      EC50 of potent agonists does not represent the KA. If a fraction of receptors are
      irreversibly inactivated in the tissue, KA as well as relative intrinsic efficacy
      of the potent agonists can be obtained. Although quantitation of irreversible
      antagonists is quite complex, the competitive reversible blockers can be
      accurately compared on the basis of equilibrium dissociation constant (KB)
      values. Along with the relative order of potency of agonists and KB values of
      antagonists, receptors can be characterized and subclassified. Preclinical
      Therapeutic Index of drugs and Toxicity Index of pesticides require
      determinations of mean lethal dose (LD50) and the mean effective dose (ED50) in
      laboratory animals, so that a relatively safe drug can be promoted for human use.
      The understanding of pharmacokinetics is essential to explain drug action in the
      target organs. Drug combinations are investigated by isobolorographic analysis.

PMID- 8979497
TI  - Therapeutic values of onion (Allium cepa L.) and garlic (Allium sativum L.).
AB  - Onion and garlic contain many sulfur containing active principles mainly in the
      form of cysteine derivatives, viz. S-alkyl cysteine sulfoxides which decompose
      into a variety of thiosulfinates and polysulfides by the action of an enzyme
      allinase on extraction. Decomposed products are volatile and present in the oils
      of onion and garlic. They possess antidiabetic, antibiotic, hypocholesterolaemic,
      fibrinolytic and various other biological actions. In addition to free sulfoxides
      in alliums, there are nonvolatile sulfur-containing peptides and proteins which
      possess various activities and thus make these vegetables as an important source
      of therapeutic agents. As allyl and related sulfoxides are inhibiting thiol group
      enzymes, alliums are to be used only in limited quantities.

PMID- 8979498
TI  - Activation of protease activity in rat peritoneal macrophages in protein
      deficiency: characterization of cathepsin D.
AB  - Rat peritoneal macrophages contained high proteolytic activity that was
      significantly enhanced under the stress induced by protein deficiency. The
      aspartyl protease cathepsin D which has been known to be the most active protease
      in endocytic processes was extracted from the macrophages recovered from control
      (20% protein fed) and protein deficient (4% protein fed) rats and was affinity
      purified and characterized further. The cathepsin D from the control sample
      exhibited better recovery, purification and higher specific activity compared to
      that from the deficient groups. Apparently the pH optima and heat stability of
      the enzyme from both the groups were similar. The SDS PAGE profile clearly
      indicated the presence of greater amounts of active forms of cathepsin D in the
      deficient samples in vivo itself which reflected in a reduction in Km value of
      the enzyme. Subtle differences observed in the activity of these macrophage
      proteases in the protein deficient rats may be partly responsible for the
      enhanced degradation of macrophage membrane proteins reported earlier.

PMID- 8979499
TI  - Benzoyl peroxide modulates gene expression by epigenetic mechanism in mouse
      epidermal JB6 cells.
AB  - The mechanism by which an oxidant tumor promoter benzoyl peroxide (BP) influences
      signal transduction, was studied in promotion insensitive (P-), promotion
      sensitive (P+) and transformed (Tx) mouse epidermal JB6 cells. The basal levels
      of antioxidant enzymes CuZn-superoxide dismutase and catalase were higher in P+
      and Tx JB6 cells. BP decreased the activities of these enzymes transiently in P+
      and Tx cells, but induced them in P- JB6 cells. BP increased poly ADPR polymerase
      activity accompanied by a drop in NAD+ levels more significantly in P- JB6 cells,
      but did not affect PKC activity. It induced c-jun and c-fos gene expression in
      JB6 variants but to different extents, suggesting that it mediates its effects
      via genetic- epigenetic mechanism(s).

PMID- 8979500
TI  - Identification and characterization of receptor for dengue virus-induced
      macrophage cytotoxin.
AB  - The present study was undertaken to identify the receptor for dengue virus type 2
      (DV) induced macrophage cytotoxin (CF2) on mouse peritoneal macrophages (MPhi).
      The binding of 125I-labelled CF2 to MPhi was saturable (15 nM), reversible,
      temperature, pH- and time-dependent. The saturation concentration was similar to
      that causing cell death. Scatchard analysis showed the presence of intermediate
      type of affinity receptor and the number of receptor sites was 1.1 x 10(6) per
      cell with dissociation constant of 14.28 nM.

PMID- 8979501
TI  - Synthetic peptides related to laminin pentapeptide (YIGSR) fragment.
AB  - The synthetic laminin pentapeptide amide fragment (LF), Tyr-Ile-Gly-Ser-Arg-NH2
      corresponding to a part of B1 chain of the glycoprotein, laminin, and six of its
      analogues having structural modifications at positions 1, 3 and 4 were
      synthesized by solid phase method employing mainly 9-fluorenylmethoxycarbonyl
      amino acid trichlorophenyl esters as coupling agents and Merrifield resin as the
      solid support. Their biological activities were studied in vivo by lung tumor
      colonization assay and in vitro by cell adhesion assay. The activity of synthetic
      LF was found to correlate with the earlier reported results in both in vivo and
      in vitro assays. Among the analogues made, [Tyr4] LF and [Thr4]LF were found to
      inhibit the lung tumor colonies more efficiently than LF itself in the in vivo
      assay whereas [D- Ser4]LF exhibited almost the same inhibition as LF.

PMID- 8979502
TI  - Felodipine potentiates morphine analgesia in control and streptozotocin diabetic
      female rats.
AB  - Tolerance to morphine analgesia was seen in diabetes. Calcium channel blockers
      potentiate opioid analgesia while calcium agonists antagonize. Therefore, the
      present study using thermal pain threshold was taken up to find out, whether
      felodipine, altered morphine analgesia in experimental diabetes. From the end of
      6th week of streptozotocin-diabetes, felodipine was administered po for 2 week to
      half of the control and diabetic female rats. Morphine analgesia was recorded 1
      hr after the first (acute effect) and last dose (chronic effect) of felodipine.
      Significant elevation of pain threshold was seen in the first 6 weeks in diabetic
      rats compared to controls. No tolerance was seen to morphine (2 mg/kg, sc)
      analgesia in diabetic rats. In both control and diabetic rats acute
      administration of felodipine produced significant analgesia while both acute and
      chronic administration of felodipine produced significant potentiation of
      morphine analgesia in control diabetic rats. The results suggest that prior
      felodipine may enhance morphine analgesia, and that this needs to be explored
      further in various types of pain.

PMID- 8979503
TI  - Augmentation of phenyldiguanide-induced bradycardia by Buthus tamulus venom in
      adult rats.
AB  - Intravenous injection of phenyldiguanide (PDG) in anaesthetized rats produced
      dose-dependent (1-10 micrograms/kg) decrease in heart rate for a period of time
      (time-response area). The maximum response occurred at 10 micrograms/kg PDG.
      Administration of B. tamulus (BT) venom as low as 20 micrograms/kg augmented the
      PDG-induced bradycardia response by 2.5 times the initial PDG (10 micrograms/kg)
      response. The maximal augmentation was observed after 60 min of venom injection.
      Increasing the BT venom concentration to 40 micrograms/kg failed to enhance the
      reflex response (1.7 times the initial response). The threshold concentration of
      BT venom was 4 micrograms/kg. BT venom (100 micrograms/kg) alone, decreased the
      heart rate significantly only after 90 min. Results indicate that, even the
      sublethal concentrations of BT venom sensitize the reflexes elicited by PDG.

PMID- 8979504
TI  - Isolation and characterization of a copper containing protein from blue cell
      walls of Neurospora crassa.
AB  - Culturing Neurospora crassa in presence of toxic amounts of copper (0.63 mM)
      resulted in blue coloured mycelia and cell walls. Significant amounts
      (approximately 45%) of total mycelial copper were associated with cell wall
      isolates under conditions of copper toxicity. Hence, such blue cell walls were
      analysed to identify specific ligands involved in copper binding. While
      decuprification of the blue cell walls with 8-hydroxy quinoline (8 HQ) did not
      alter their copper binding abilities, similar treatment with EDTA (10 mM)
      decreased such abilities indicating that EDTA treatment lead to loss of copper
      binding ligands from cell walls. Treatment of blue cell walls with 8 HQ followed
      by EDTA resulted in the solubilization of a copper binding protein (relative MW
      approximately 14 kDa) which was associated with phosphate and carbohydrate
      moieties. On amino acid analysis, this protein was found to be devoid of free
      thiol groupings but enriched in acidic and basic amino acids, distinguishing it
      from classical intracellular metal binding proteins such as metallo-thioneins and
      phytochelatins that are inducively synthesized under conditions of metal
      toxicity. The biological significance of the isolated wall-bound copper binding
      protein, which appears to be a normal constituent of cell walls, is discussed in
      relation to cytoplasmic metal binding proteins and mechanism(s) adapted by fungi
      in countering metal toxicity.

PMID- 8979505
TI  - Isolation of 75Se binding protein from hepatic tissues of chick embryos.
AB  - Distribution study using 75Se shows that maximum accumulation was in liver
      tissues after 24h of 75Se administration. Induction of selenium binding protein
      (Se-P) in hepatic tissues of chick embryo was observed. Chick embryo hepatic Se-P
      was isolated after 24h of 75Se treatment using Sephadex G-75 column
      chromatography. Fractions of induced protein shows the presence of maximum
      concentration of 75Se. This induced protein was found to have an approximate
      molecular weight of 56 KD on molecular sieve. It also showed an absorbance maxima
      at 254 nm, which indicates the presence of high concentrations of sulphydryl
      groups.

PMID- 8979506
TI  - Gastric antiulcer activity of UL-409 in rats.
AB  - Effect of UL-409, a multiconstituent herbal preparation was evaluated on
      different models of gastric ulcers in rats. In doses 25, 50 and 100 mg/kg. p.o.
      it significantly reduced the gastric secretory volume and ulcer index in pylorus
      ligated rats, and showed significant mucoprotective effect at 100 mg/kg dose on
      both acute and chronic treatment. UL-409(50 and 100 mg/kg doses) prevented
      immobilization induced gastric ulceration and showed significant mucosal
      protection. In forced swimming induced ulcers, UL-4093(50 and 100 mg/kg)
      completely abolished the ulcerogenesis and strengthened the mucosal barrier. It
      also protected the indomethacin-induced gastric ulcers and significantly
      increased the mucosal content. Cimetidine (10 mg/kg) and diazepam (20 mg/kg) were
      used for comparison. The results indicate that UL-409 has anti-ulcerogenic
      effects due to its mucoprotective effect. The preparation can be used alone or in
      combination with other ulcer healing agents.

PMID- 8979507
TI  - Chromium uptake and toxicity effects on growth and metabolic activities in wheat,
      Triticum aestivum L. cv. UP 2003.
AB  - Chromium (Cr) at graded levels when added in sand culture of wheat (T. aestivum
      L. cv. UP2003) under glasshouse conditions resulted in reduction in biomass,
      chlorophyll and activities of catalase and peroxidase while enhanced acid
      phosphatase and ribonuclease activities. Elevated levels of Cr supply
      significantly reduced the concentration of inorganic phosphorus. With an increase
      in Cr supply the uptake of chromium also increased significantly in different
      plant parts especially in roots. Above metabolic lesions due to Cr in wheat
      provided evidence that the element in nutrient medium if present in excess may be
      inhibitory to plant growth and development.

PMID- 8979508
TI  - Quantitative assessment of changes and maturation of mast cells in the ovary of
      postnatal and adult rats, Rattus rattus.
AB  - Numerical changes in the distribution of immature mast cells in the different
      ovarian compartments of the immature and adult ovary of rats Rattus rattus have
      been studied using alcian blue-safranine staining method. Maturational changes of
      mast cells from the first day of birth to maturity of animal and during the
      oestrous cycle have also been determined. Immature animals were divided into five
      groups on the basis of their increasing body weights. All the mast cells in the
      ovary group of I and II were immature as they showed positive staining with
      alcian blue and appear to possess the proliferative capacity. Cells containing
      safranine-stained red granules were first observed in group III rats and they
      appeared simultaneously in hilus, medulla and cortical regions of the ovary.
      Total counts of immature mast cells per ovary increased significantly from group
      I to II, decreased in group III and thereafter no change was recorded in group IV
      and V. Mast cells in the ovary of rats of group I and II were mainly localized in
      the stroma, followed by medulla and hilus. In mature rats major part of cell
      population was concentrated in the hilar region. Alcian blue-positive mast cells
      were observed at all stages of oestrous cycle, their number per ovary was found
      to be highest at oestrus, intermediary at dioestrus and metoestrus, and lowest at
      pro-oestrus which suggested that new population of mast cells continue to
      differentiate in the cycling rat ovary.

PMID- 8979509
TI  - Diurnal variations in circulating estradiol, testosterone, melatonin and
      harderian gland porphyrin concentration in Indian palm squirrel, Funambulus
      pennanti.
AB  - A two-peak cyclicity in the plasma level of melatonin, estradiol/testosterone and
      Harderian porphyrin was noted in F. pennanti. An inverse relationship of
      Harderian porphyrin with plasma melatonin and a direct relation of it with plasma
      estradiol/testoserone level were also observed, suggesting that the variation of
      Harderian, porphyrin concentration may be under the control of both, circulating
      melatonin and gonadal steroids.

PMID- 8979510
TI  - Modulation of humoral and cell-mediated immune responses by Azadirachta indica
      (Neem) in mice.
AB  - The effects of A. indica (AI, Neem) were evaluated on tests of humoral and cell
      mediated immune responses after 3 weeks of oral AI (leaf extract) treatment in
      ovalbumin immunized mice. At the dose levels tested, AI (10, 30 or 100 mg/kg),
      had no appreciable influence on different organ (liver, spleen, thymus)/body
      weight indices, when compared to controls. In tests for humoral immune responses,
      AI (100 mg/kg) treated mice had higher (1) IgM and IgG levels, and (b) anti
      ovalbumin antibody titres, when compared to the vehicle treated group. In tests
      for cell-mediated immune responses, there was an enhancement (%) of (a)
      macrophage migration inhibition, and (b) footpad thickness after AI (100 mg/kg)
      treatment. These results are discussed in light of the possible
      immunopotentiating effects of AI.

PMID- 8979511
TI  - Enhanced photosynthesis in cytozyme-treated blackgram, Phaseolus mungo L.
AB  - Foliar application of cytozyme to 30-day-old black-gram plants resulted 48%
      increase of dry matter accumulation. The increase in fresh and dry weights of
      total plants was largely due to enhanced CO2 assimilation rates which were
      associated with increased RuBP carboxylase activities. The photochemical
      characteristics in the isolated chloroplasts exhibited an increase of 32, 28 and
      40%, measured as the photoreduction of DCPIP, FeCN and NADP, respectively.
      Cytozyme treatment also resulted an increase in the chlorophyll content in
      leaves.

PMID- 8979512
TI  - Fungicidal and insect controlling properties of Proteus strain RRLJ 16, isolated
      from tea, Camellia sinensis (L) O Kuntze, plantations.
AB  - A strain of Proteus RRLJ 16, isolated from acid (pH 4.5-5.5) iron rich tea
      (Camellia sinensis) plantation soil, produced siderophores with single absorption
      peak at 370 nm when cultured in iron free medium. Extracted crude fraction of
      siderophores and live cultures showed in vitro antibiosis against five species of
      pathogenic fungi. When the strain was cultured in a normal bacteriological medium
      without iron stress, it produced an insect repellent compound. The culture
      filtrate sprayed (dilution of 1:100 in water) on tea plants infected with pink
      mites or green flies, the insect populations disappeared from the plants. Termite
      galleries sprayed similarly showed no termite activity after 24 hr of spraying.
      No reinfestation by insects was observed on treated plants for more than one
      year.

PMID- 8979513
TI  - A simple technique for improving chromosome spreads from clumped metaphases.
AB  - A method has been described by which clumped metaphases either due to inadequate
      hypotonic KCl treatment or prolonged storage at 4 degrees C can be rescued. The
      cell pellet obtained from cell suspension following centrifugation was
      resuspended in freshly prepared Carnoy's fixative (1:3, acetic acid: methanol) at
      room temperature by vortexing. Twenty microliters of Triton X-100 at a
      concentration of 0.5% was added drop by drop while vortexing. Three changes with
      fixative containing 0.5% Triton X-100 were optimal for obtaining good metaphase
      spreads with complete removal of the cytoplasmic background. The advantage of
      this technique is that important patients' samples having clumped metaphases
      otherwise not useful for G-banding can be rescued and karyotyped by this method.

PMID- 8979514
TI  - A novel approach to study antibacterial properties of volatile components of
      selected Indian medicinal herbs.
AB  - The aromatic substances of natural origin are used medicinally in Ayurveda, and
      can have diverse bio-dynamic actions. The existing methods like agar-cup method
      or disc diffusion method are not adequate to study the exclusive antibacterial
      effects of the volatile components of aromatic oils due to lack of ideal
      diffusion and evaporation from the surface. Hence an attempt is made to develop a
      novel approach to assess the antibacterial activity of few aromatic herbs like
      Eugenia caryophyllus, Thymus vulgaris, Cinnamonum zeylanium, Cuminum cyminum;
      these were extracted with hexane filled in tiny sterile tubes and the volatile
      components were tested for their antibacterial properties using standard strains
      of gram +ve and gram -ve bacteria grown on agar slants. The results are expressed
      as a percent of inhibition of the area on the slants, from the top of the extract
      tube. Of the four herbs selected, volatile components of Thymus vulgaris were
      most effective againsts all the seven test organisms.

PMID- 8979515
TI  - Direct somatic embryogenesis and transformation in Cicer arietinum L.
AB  - Somatic embryos were induced directly from immature cotyledons of the genotype of
      chickpea ICC 4918 (annigiri) on B5 medium supplemented with 2,4,5-T or 2,4-D in
      combination with BA or KN. Successful transformation was achieved via somatic
      embryogenesis using Agrobacterium tumefaciens strain LBA4404, carrying a binary
      plasmid vector system containing neomycin phosphotransferase (NPT II) gene as the
      selectable marker and beta-glucuronidase (GUS) as a reporter gene. Histochemical
      staining for GUS expression was observed as primary evidence for transformation.

PMID- 8979516
TI  - Somatic embryogenesis and plantlet from petal cultures of pomegranate, Punica
      granatum L.
AB  - Somatic embryos were induced through petal cultures on MS supplemented with
      various growth adjuvants individually or in different combinations. Numerous
      embryoids formed from friable callus on MS with 5 mg/L of IAA, IBA or NAA
      developed only roots, but those formed on MS with 5 mg/L of BAP or KN developed
      shoots. Explants reared on MS supplemented with IAA (5 mg/L) and BAP (5 mg/L)
      though differentiated numerous embryoids but developed multilobed or fused
      cotyledons. However, callus induced on MS with IAA (1 mg/L) or IBA (1 mg/L) on
      subculturing in the same medium with half-strength salts and sucrose (4%)
      produced both roots and shoots resulting in plantlets.

PMID- 8979517
TI  - In vitro & in vivo experimental susceptibility of Mycobacterium marinum to
      augmentin.
AB  - The effect of augmentin alone and in combination with various beta-lactam
      antibiotics was studied against a pathogenic Mycobacterium, M. marinum. The in
      vitro studies did not reveal any additional advantage over that found with
      augmentin alone and this antibiotic seemed considerably inhibitory to M. marinum
      at < 1 microgram/ml concentration. In vivo, the effects of augmentin on
      experimentally produced lesions in the mouse foot pads (MFPs) showed a
      significant regression of the lesions, which was compatible with an early
      disappearance of M. marinum from the MFP, in contrast with those of the
      untreated, control animals.

PMID- 8979518
TI  - Effect of arteether alpha/beta on uncomplicated falciparum malaria cases in Upper
      Assam.
AB  - Thirty patients of uncomplicated Plasmodium falciparum malaria completed a
      clinical trial of arteether alpha/beta conducted in a malaria endemic tea garden
      of district Dibrugarh, Assam. Arteether was given intramuscularly in once a day
      dose of 150 mg for three consecutive days. The cure rate was 100 per cent with
      mean fever and parasite clearance time of 42.4 +/- 17.5 and 37.6 +/- 13.6 h
      respectively. Recrudescence/reinfection rate was 6.7 per cent. Palpable spleens
      of twenty out of twenty one cases on day 0 became non palpable within 28 days.
      Following the treatment, percentage of hemoglobin improved marginally with no
      remarkable change in total and differential leucocyte count. Arteether
      alpha/beta, besides being a potent and fast acting schizontocidal drug, also
      exhibited gametocytocidal action on P. falciparum.

PMID- 8979519
TI  - Karyotyping of at risk fetuses by cordocentesis in advanced gestation.
AB  - Fetal blood obtained by cordocentesis was cultured to obtain rapid karyotypes of
      fetuses at risk during the late second trimester. Ninety nine fetal blood samples
      were studied for chromosomal abnormalities. The commonest indications for the
      procedure were abnormalities detected on ultrasonography (47.7%), and previous
      child with Down syndrome. Analysis of the 67 successful cultures showed four
      (5.9%) karyotypic abnormalities. The technique proved helpful in the obstetrical
      management of at risk fetuses.

PMID- 8979520
TI  - Peripheral blood lymphocyte subsets in idiopathic nephrotic syndrome of
      childhood.
AB  - Lymphocyte subsets in the peripheral blood were examined in 34 patients with
      nephrotic syndrome [27 with minimal change nephrotic syndrome (MCNS), 7 with
      significant lesions] and 10 normal children. The investigations were done at the
      onset of disease before administering corticosteroids (n = 34), during the
      subsequent remission (n = 27), and the first relapse (n = 12). The proportions of
      T cell subsets (CD3, CD4 and CD8) were determined by immuno-alkaline phosphatase
      staining; interleukin-2 receptor (IL-2 R) positive cells, natural killer (NK)
      cells and B cells were studied by indirect immunofluorescence. No significant
      differences were found in the proportion of CD3, CD4, CD8 and IL-2 R positive
      cells in patients with MCNS as compared to controls. An increased proportion of
      NK and B cells was not specific to MCNS and was detected even in those with
      significant renal lesions. Our findings suggest that T lymphocyte subsets in MCNS
      are similar to those in normal children.

PMID- 8979521
TI  - A flowcytometric study of CD4+ & CD19+ cell lymphopenia in patients with alopecia
      areata.
AB  - Twenty five patients with alopecia areata and 20 healthy controls were studied by
      flowcytometry employing direct two colour immunofluorescence in erythrocyte lysed
      whole blood. A significant reduction was observed in helper/inducer (CD4+)
      lymphocytes (29.4 +/- 7.4 vs 39.45 +/- 8.0, P < 0.01) and B (CD 19+) lymphocytes
      (11.04 +/- 6.57 vs 15.0 +/- 5.05, P < 0.01) in comparison with healthy controls.
      Decrease in T-lymphocytes (CD3+) and suppressor/cytotoxic (CD8+) was not
      significant and activated (HLADR+) lymphocytes and natural killer cells (CD16+
      and CD56+) were within normal limits. Our findings suggest a significant T helper
      (CD4+) and B (CD19+) cell lymphopenia in alopecia areata.

PMID- 8979522
TI  - Dyspnoea, lung function & respiratory muscle pressures in patients with Graves'
      disease.
AB  - To understand the pathophysiology of dyspnoea in patients with hyperthyroidism,
      lung function, maximum inspiratory, expiratory respiratory muscle pressures (MIP
      and MEP) and intensity of dyspnoea (after six minutes walking test) were recorded
      in 12 consecutive patients with active Graves' disease. Reassessment was done
      after achieving euthyroidism with 8-12 wk of carbimazole therapy. Patients
      covered similar distance during 6 min walking before and after carbimazole
      therapy. However, there was a significant reduction in dyspnoea following
      euthyroidism. This was accompanied by significant decrease in respiratory rate,
      minute ventilation, forced expiratory volume in one second (FEV1%) and
      improvement in the forced vital capacity (FVC). No significant changes in tidal
      volume (TV) and maximum-midexpiratory flow rates (MMEFR), MIP and MEP were
      observed. Lung function parameters, MIP and MEP did not correlate with the
      severity of dyspnoea. Serum T4 levels correlated inversely with the distance
      covered during 6 min walking test, MIP and MEP. To conclude, increased breathing
      effort in presence of reduced FVC may lead to dyspnoea during hyperthyroid phase
      in patients with active Graves' disease. Lack of correlation between the severity
      of dyspnoea and abnormalities in lung function suggests that other mechanisms of
      dyspnoea may also operate in these patients.

PMID- 8979523
TI  - Erythropoietin & erythroid progenitors in rats exposed to chronic hypoxia.
AB  - In order to better understand the mechanisms affecting erythropoietin (Epo)
      synthesis and red cell mass increase under chronic hypoxia, we examined Epo
      production and erythroid progenitors (CFU-E) in rats exposed to normobaric
      hypoxia for four weeks. Hypoxia induced the rise of hematocrit (Htc), hemoglobin
      (Hb) concentration and the red blood cell (RBC) number with a plateau in
      hematocrit values after two weeks. After 24 h of hypoxia, Epo levels were
      increased 20 fold, followed by a significant decrease. After the first week of
      hypoxia, the values were still higher than in the controls, but after two weeks
      Epo levels did not differ significantly from the normal values. The fall of Epo
      levels coincided with the plateau values of hematocrit. The changes in the CFU-E
      number followed the changes in Epo concentration: a two fold increase after 24 h
      of hypoxia; a further increase during the next two weeks reaching a peak on day
      14, and then a progressive decrease at the time when Epo concentration was at a
      normal level. Although decreased, but still higher than normal, the CFU-E number
      during the last two weeks of hypoxia could be necessary for the maintenance of an
      achieved steady state under persistent hypoxic conditions with normal Epo
      concentration sufficient to maintain the existing rate of erythropoiesis.

PMID- 8979524
TI  - Brainstem auditory evoked responses in primary hypertension.
AB  - Brainstem auditory evoked potential responses (BAEPs) were recorded from CZ-A1
      and CZ-A2 scalp regions in 23 hypertensive and 14 normotensive subjects.
      Hypertension was graded depending upon the extent of raised blood pressure. BAEPs
      in patients of grade I and II hypertension did not show any change when compared
      to normotensive subjects. However, grade III hypertensive case showed significant
      prolongation of absolute peak latencies of wave I, II, V and interpeak latency of
      wave III-V indicating involvement of brainstem auditory pathways. Multiple
      regression analysis revealed significant correlation of rise in systolic and
      diastolic blood pressure with absolute peak latencies of BAEPs in hypertensive
      patients.

PMID- 8979525
TI  - Trends of smoking among medical students.
AB  - The overall smoking prevalence among male medical students between the years 1955
      and 1988 in a medical college in South India was 39.51 per cent. The trends of
      smoking appeared to be in three phases. An initial phase comprising of a steady
      rise to a peak in the late sixties and seventies, followed by a plateau of the
      prevalence in the next ten years and ultimately a sharp fall in the last five
      years. Study based on a mailed-in questionnaire to ten batches of students
      selected randomly, to study the factors affecting initiation and quitting of
      smoking showed that the peak period of initiation seemed to be in the two years
      before and after joining the course. There was a significant relationship between
      the presence of a smoker in the family and picking up the habit. Conversely, no
      significant relationships were found with respect to quitting.

PMID- 8979526
TI  - Research stimulating programme for interns.
AB  - The present study shows that acquisition of research skills and competence is
      lacking in the usual training which is imparted to under graduate medical
      students. It also shows that the acquisition of these skills can be facilitated
      by suitable structured training programmes during their internship period. Funds
      for such activities are often available from various agencies, provided that the
      individual research study areas chosen are of interest to them.

PMID- 8979527
TI  - Pseudocysts of pancreas in children.
AB  - A total of 7 patients pseudopancreatic cysts was managed in children over a
      period of 5 years. Trauma was responsible for the development of pseudocyst in
      one while in rest of the patients no etiologic factor could be identified. All
      the patients underwent trans-gastric cyctogastrostomy. With a mean follow-up of
      30 months, no death and no recurrence was found. It seems that surgical
      experience of pseudopancreatic cysts in children is similar to that seen in
      adults.

PMID- 8979528
TI  - Bacteriological patterns of chronic suppurative otitis media in Ludhiana.
AB  - A series of 300 cases of chronic suppurative otitis media encountered in Dayanand
      Medical College and Hospital, Ludhiana was surveyed for type specificity to
      determine latest trends of bacterial prevalence in Ludhiana. Punjab Pseudomonas,
      staphylococcus and proteus head the list. The problem of resistance is discussed
      in the present context.

PMID- 8979529
TI  - A study of registration of deaths at primary health centre--with special
      reference to "verbal autopsy" method.

PMID- 8979530
TI  - Deterioration of carbohydrate metabolism by nifedipine.

PMID- 8979531
TI  - Some basic mechanisms of autoimmune diseases: a review.

PMID- 8979532
TI  - General principles of management of autoimmune haematological disorders.

PMID- 8979533
TI  - Immune neutropaenia: diagnosis natural history, clinical features and management.

PMID- 8979534
TI  - Autoimmune haemolytic anaemia: laboratory aspects.

PMID- 8979535
TI  - Management of autoimmune hemolytic anemia.

PMID- 8979536
TI  - Autoantibodies and blood coagulation.

PMID- 8979537
TI  - Immune modulation in bone marrow transplant.

PMID- 8979538
TI  - Changes in serum protease inhibitors and liver specific enzymes in experimental
      jaundice.
AB  - Changes in the different fractions of the serum protease inhibitors were studied
      in experimentally produced cases of obstructive jaundice in rabbits to correlate
      with other liver specific diagnostic parameters. The heat stable antiprotease
      fraction and alkaline phosphatase levels in serum were the only parameters which
      did not show significant fluctuations in the normal as well as in the
      experimental controls and were significantly elevated due to bile duct ligation.
      However, due to smaller change in the magnitude, the heat stable antiprotease
      levels were not found to be of much diagnostic use and the determination of
      bilirubin, alkaline phosphatase and alanine aminotransferase levels in serum
      appeared to be better indicators for detection of liver damage in such cases due
      to appreciable alterations in their levels.

PMID- 8979539
TI  - Evaluation of acridine-orange staining of centrifuged parasites in malarial
      infection.
AB  - A total of 18,845 blood samples were tested by the Acridine Orange (AO)
      quantitative buffy coat (QBC) method, under white light and UV light and compared
      with thick blood films, for the detection of malarial parasites. The positivity
      rate was 25% by the AO-QBC technique and was 18% by the thick film technique. The
      increased sensitivity, combined with the rapidity and simplicity of the AO-QBC
      technique, establishes its superiority over the conventional thick film method,
      in the sentinel surveillance of malaria, in endemic areas. The comparative unit
      price of the AO-QBC test and conventional microscopy is Rs. 38.00 and Rs. 14.00
      respectively. But, the ancillary advantages of the AO-QBC method over the
      conventional method more than offset the cost difference.

PMID- 8979540
TI  - Radio-protective effect of garlic Allium sativum Linn. in albino rats.
AB  - S-allyl cysteine sulphoxide (SACS), a sulphur containing aminoacid of garlic is
      the precursor of allicin and garlic oil, and has been found to show significant
      radio protective effect in albino rats which were whole body irradiated with 400
      rads of irradiation by Cobalt 60 source. It markedly reduced the radiation
      induced mortality and showed significant protection against the tissue damaging
      effects of irradiation in histopathological sections of liver and lung.

PMID- 8979541
TI  - Bioequivalence studies of celiprolol in healthy human volunteers.
AB  - Thus bioequivalence between the two products was established by undertaking this
      study. From table 1 it can be seen that the standard deviation at the various
      sampling points is high indicating varying absorption rates in individual
      volunteers, but this was observed in case of both the products. Also, since the
      study design was complete crossover, this high standard deviation was not due to
      any study design variable. As celiprolol shows non-linear1 dose related
      absorption kinetics this high value of standard deviation may be due to the
      intersubject variation during the absorption process. However all the
      pharmacokinetic parameters showed a comparable profile when statistically
      evaluated for any significant difference between the two products.

PMID- 8979543
TI  - Poncet's disease--case report.
AB  - Poncet's disease is a rare polyarthritis occurring in patients with tuberculous
      infection. We describe two cases of polyarthritis, one secondary to pulmonary
      tuberculosis, the other secondary to tuberculous infection of lymph nodes. In
      both cases the arthritis rapidly subsided with chemotherapy.

PMID- 8979542
TI  - Activity of third generation cephalosporins against Pseudomonas aeruginosa in
      high risk hospital units.
AB  - Ceftazidime and Cefoperazone are the two third generation cephalosporins with
      anti-pseudomonal activity. They have been frequently used in the I.C.U.s. in the
      developed countries but their use in the Indian hospitals has begun relatively
      recently. We studied the in-vitro susceptibility of 139 Pseudomonas aeruginosa
      isolates that were multiple drug resistant from the Resuscitation Unit/I.C.U. (61
      strains), Burns Unit (48 strains), Surgical Post-operative unit (24 strains),
      Nephrology unit (6 strains) of our hospital to these two cephalosporine over a
      period of about 18 months. Antibiotic susceptibility was studied using Kirby
      Bauer's disc dibusion method. Out of a total of 139 strains of multiple drug
      resistant Pseudomonas aeruginosa tested, 17.9% were found resistant each to
      Ceftazidime and Cefoperazone separately and 10% were found resistant to both
      antibiotics.

PMID- 8979545
TI  - Comprehensive child care.

PMID- 8979544
TI  - Management of isoniazid poisoning--case report.
AB  - A young girl was admitted with generalized tonic clonic seizures and
      unconsciousness, four hours after ingestion of 12 gm of isoniazid (INH). In the
      absence of injectable preparation of pyridoxine, she was treated with oral
      pyridoxine and made a complete recovery.

PMID- 8979546
TI  - Radionuclide studies in the evaluation of urinary tract infections.
AB  - OBJECTIVE: To estimate the prevalence of vesicoureteral reflux (VUR) and renal
      scarring in children presenting with culture proven urinary tract infections
      (UTI). DESIGN: Descriptive study. SETTING: Tertiary care hospital-based study.
      SUBJECTS: Thirty-two children with proven UTI were evaluated by means of an
      abdominal ultrasonogram (USG), Technetium-99m Dimercapto Succinic Acid (DMSA)
      scan and Direct Radionuclide Cystography (DRCG). A micturating cystourethrogram
      (MCU) was performed to rule out any structural abnormality and to grade VUR.
      RESULTS: A total of 64 renal units in 32 children were evaluated. DMSA scan
      showed scarring in 27 renal units (42.2%) in 16 patients. Bilateral renal
      scarring was more common in older (> 2 yr) children as compared to younger ones
      (89% Vs 43%; p < 0.05). USG detected abnormalities in 13 renal units (20.3%) in 7
      cases. VUR was detected in 37.5% of children of all age group by DRCG. In
      contrast, MCU showed evidence of VUR in only 13/20 renal units with a sensitivity
      of 65% as compared to DRCG and did not pick up any additional VUR that could have
      been missed on the DRCG. Only 3/9 in < 2 yr, in contrast to 10/11 in > 2 yr were
      positive for VUR on MCU (p < 0.05). However, MCU detected evidence of cystitis in
      3 children and a bladder diverticulum in one patient. CONCLUSION: Wherever
      available, DMSA scan should be considered as a part of the first line
      investigations in any patient presenting with UTI. DRCG can also be performed in
      the same sitting to screen for the presence of reflux particularly for girls.

PMID- 8979547
TI  - Neurologic sequelae in high risk infants--a three year follow up.
AB  - OBJECTIVE: To determine the neurologic sequelae in high risk infants. DESIGN: A
      three year longitudinal follow up. SETTING: Inborn and outborn infants discharged
      from the Neonatal Special Care Unit (NSCU) of a referral hospital. METHODS: High
      risk infants were identified for follow up using predetermined risk criteria. A
      detailed neurodevelopmental examination was done 3 monthly in the first year and
      6 monthly subsequently. The Amiel-Tison Method, Bayley Scales of Infant
      Development and Raval's Scale for social maturity were used. EEG was done in
      children with seizures. Hearing and ophthalmic assessments were done at 6 months.
      RESULTS: Three hundred and thirty six high risk infants and 70 normal control
      infants came for regular follow up. Out of these, 16 (4.8%) had cerebral palsy
      and 11 had associated mental retardation. Six other children had mental
      retardation without motor problems. None of the children in the control group had
      any neurological problems. Sensorineural hearing loss was present in 5 (1.5%)
      children while 1 subject had corfical blindness. Three children with cerebral
      palsy had infantile myoclonus, nine had generalized seizures and one child had a
      focal seizure. The incidence of seizure disorders was 3.9%. CONCLUSIONS: The
      incidence of major handicap in our study was low. Many of the risk factors which
      caused adverse outcome, could have been prevented by good antenatal and perinatal
      care.

PMID- 8979549
TI  - Fetal pulse oximetry.

PMID- 8979548
TI  - Cost of infant feeding in exclusive and partially breastfed infants.
AB  - OBJECTIVE: To compare the costs incurred on infant feeding between the mothers
      who exclusively breastfed their infants and those who introduced supplements up
      to 6 months of age. DESIGN: Longitudinal follow up. SETTING: Urban slums of south
      Delhi. METHODS: One hundred normal mother infant pairs fulfilling the prelaid
      criteria were recruited at the time of birth and followed up for determining the
      feeding practices. The cost of feeding was estimated at prevalent market prices
      in terms of food supplement and medical treatment of infant and additional
      nutritional intake of mothers. The differences in costs in exclusively and
      partially breastfed groups were analyzed at 3, 4, 5 and 6 months of age. RESULTS:
      There was a sharp decline of exclusive breastfeeding from birth to six months.
      The mean cost of infant feeding was Rs. 204/- per month in partially breastfed as
      compared to Rs. 106/- in exclusively breastfed at 6 months of age. The increased
      cost was largely attributable to supplementary food and the cost of feeding
      bottles. (83% of mothers used bottles). CONCLUSIONS: The mean cost of infant
      feeding is substantially higher in partially breastfed children.

PMID- 8979550
TI  - Neonatal sepsis.

PMID- 8979551
TI  - Randomized controlled trial of Asparagus racemosus (Shatavari) as a lactogogue in
      lactational inadequacy.

PMID- 8979552
TI  - Neonatal supraventricular tachycardia.

PMID- 8979553
TI  - Disseminated staphylococcal disease.

PMID- 8979554
TI  - Kawasaki disease--treatment with intravenous immunoglobulin during the acute
      stage.

PMID- 8979555
TI  - Tricuspid valve endocarditis in a child with structurally normal heart.

PMID- 8979556
TI  - Dysembryoplastic neuroepithelial tumor.

PMID- 8979557
TI  - Septo-optic dysplasia.

PMID- 8979558
TI  - Furazolidone in typhoid fever.

PMID- 8979559
TI  - Japanese encephalitis in Orissa.

PMID- 8979560
TI  - Early onset neonatal septicemia caused by Aeromonas hydrophilia.

PMID- 8979561
TI  - Flavobacterium meningosepticum: an unusual pathogen.

PMID- 8979562
TI  - Developmental assessment tests: scope and limitations.

PMID- 8979563
TI  - Comparison of phenobarbitone, phenytoin with sodium valproate: randomized, double
      blind study.
AB  - OBJECTIVE: To compare the efficacy and side effects of phenobarbitone (PB),
      phenytoin (PHT) and sodium valproate (SVP) in controlling generalized tonic
      clonic convulsions (GTC). DESIGN: Randomized, double blind clinical trial.
      SETTING: Out-Patients in a tertiary care hospital. PATIENTS: 151 children with
      GTC, aged 4-12 yrs, from Madras city were enrolled. At the end of 2 yrs, 127
      children remained in the study. INTERVENTION: Each child was given one active
      drug and 2 placebo tablets. Clinical, hematological and biochemical evaluations
      were done every month. Serum drug levels were assessed periodically. MAIN OUTCOME
      MEASURES: Recurrence of convulsion and side effects. RESULTS: The proportion of
      children with recurrence did not differ among the 3 groups. More than one side
      effect was observed in 16 (32%) children on PB, 20 (40%) children on PHT and 9
      (19%) children on SVP and this difference was statistically significant (p <
      0.05). Hyperactivity was the major side effect of PB, observed in 22% of
      children. CONCLUSION: All 3 drugs were equally effective in controlling seizures.
      Side effects were minimal with SVP followed by PB. Though side effects were more
      frequent with PHT, most of them disappeared on adjusting drug dosage. Least
      expensive phenobarbitone may be preferred as the first drug of choice but, only
      for pre-school children. SVP is advised for school going children.

PMID- 8979564
TI  - Low incidence of CNS relapse with cranial radiotherapy and intrathecal
      methotrexate in acute lymphoblastic leukemia.
AB  - OBJECTIVES: To assess the incidence of isolated central nervous system (CNS)
      relapses in patients of acute lymphoblastic leukemia (ALL) treated with a
      protocol containing cranial irradiation and intrathecal methotrexate as CNS
      directed therapy. DESIGN: Prospective non randomized study. SETTING: Department
      of Medical Oncology, Tata Memorial Hospital. SUBJECTS: 623 children of ALL on MCP
      841. METHODS: CNS relapse was diagnosed, if upon examination of the CSF, more
      than 50 cells/microliter were observed, or a count of 5 cells which were
      unequivocally lymphoblasts. RESULTS: The incidence of isolated CNS relapse was
      1.75% with the use of this treatment. Age, sex, white blood cell count, platelet
      count, lactic dehydrogenase and immunophenotyping were not significantly related
      to isolated CNS relapse. CONCLUSION: A low incidence of isolated CNS relapse
      demonstrates the adequacy of the presymptomatic CNS therapy.

PMID- 8979565
TI  - Chemotherapy in Hodgkin's disease.
AB  - OBJECTIVE: To assess the efficacy of primary chemotherapy in patients with
      clinically staged Hodgkin's disease. DESIGN: Non randomized study. SETTING:
      Pediatric Oncology Division of Regional Cancer Center. SUBJECTS: Twenty nine
      children with Hodgkin's disease. INTERVENTIONS: Chemotherapy was given to 21
      patients whose parents agreed for the same. Sixteen children received COPP
      regimen and 5 received MOPP regimen. RESULTS: Complete remission was achieved in
      19 patients. The relapse free survival and overall survival in these patients
      were 76% and 86%, respectively at 5 years. There was no death related to
      chemotherapy toxicity. CONCLUSION: Combination chemotherapy is an effective
      modality of treatment for children with Hodgkin's disease.

PMID- 8979566
TI  - Wheat threshing dust--a "new allergen" in April-May nasobronchial allergy.
AB  - OBJECTIVE: To identify the allergen(s) responsible for mid April-mid May
      nasobronchial allergy seen in North India. DESIGN: Case control study. SETTING:
      Children living in and around Chandigarh (urban, rural). SUBJECTS: 39 children
      suffering from wheat harvest period (mid April-mid May) respiratory allergy along
      with randomly selected controls. METHODS: Aerobiological surveys were done from
      March to June for identification of prevailing allergens for performing allergy
      tests. Patients were subjected to skin tests (ST), nasal provocation tests (NPT)
      and bronchial provocation tests (BPT) with extracts prepared from identified
      pollens and fungal spores. Specific IgE (SIgE) was assayed by ELISA and
      comparison between pre-season, season and post-season values made. RESULTS: 81%
      patients had ST positive to antigen of wheat threshing dust (WTD), 30% to fungal
      antigens, 14% to wheat dust antigens and none to the wheat plant (WP) antigens.
      Nasal provocation test and bronchial provocation tests were also positive to WTD
      in 80% and 66% patients, respectively. WTD SIgE was demonstrated in 77% of ST
      positive patients. CONCLUSIONS: These in vivo and in vitro tests confirm wheat
      threshing dust as a major causative inhalant allergen for the April-May
      nasobronchial allergy; in addition, fungal allergens also play a role in 1/3rd of
      these patients.

PMID- 8979567
TI  - Congestive heart failure: diagnosis and management.

PMID- 8979568
TI  - Accuracy of maternal perception of neonatal temperature.

PMID- 8979569
TI  - Iodine content of salt consumed and iodine status of school children in Delhi.

PMID- 8979570
TI  - Unstable hemoglobin as a cause of congenital hemolytic anemia.

PMID- 8979571
TI  - Congestive cardiac failure and electrocardiographic abnormalities in acute
      glomerulonephritis.

PMID- 8979572
TI  - Right atrial mass due to fungal endocarditis in an infant.

PMID- 8979573
TI  - Esophageal atresia and tracheo-esophageal fistula with right pulmonary agenesis.

PMID- 8979574
TI  - Pancytopenia in disseminated tuberculosis.

PMID- 8979575
TI  - Fixation anomaly at duodenojejunal junction.

PMID- 8979576
TI  - Urine culture in young febrile children.

PMID- 8979577
TI  - Iron deficiency anemia in pregnancy.

PMID- 8979578
TI  - Lead poisoning in children: a barometer of environmental pollution.

PMID- 8979579
TI  - Delayed pneumo-mediastinum in congenital diaphragmatic hernia.

PMID- 8979580
TI  - IAP's immunization time table in pediatrics.

PMID- 8979581
TI  - Infectious diseases kill over 17 million people a year: WHO warns of global
      crisis.

PMID- 8979582
TI  - Emerging and re-emerging microbial threats to health: are children vulnerable?

PMID- 8979583
TI  - Community based estimation of perinatal mortality through record linkage.
AB  - OBJECTIVE: To estimate perinatal mortality through record linkage of Health
      Workers (HW) and Anganwadi Workers (AWW) in rural Haryana. DESIGN: Retrospective
      analysis of records (1991-92) of HW and AWW. Enquiry and home visits were made
      for tracing the fate of pregnancy in cases with incomplete records. SETTING: In
      1993-95 in 45 villages selected purposively in Raipur Rani block, Ambala. MAIN
      OUTCOME MEASURE: Enlisting of perinatal deaths as the main outcome measure
      through scrutiny of records of HW and AWW. RESULTS: Perinatal mortality rate
      (PMR) was 42.25 and 45.78 per thousand births as per the record of HW and AWW,
      respectively for the 23 villages for whom records of both were available. Support
      by enquiry or home visit yielded a PMR of 59.42 for combined HW and AWW sources
      and 51.66 per 1000 births for AWW source alone. Concordance between AWW and HW
      records for fate of pregnancy was moderate (K = 0.46; 95% CI 0.35-0.57).
      CONCLUSIONS: There is a lack of a system of record linkage between and within the
      records of HW and AWW at primary health care level. AWW data was more accurate
      and up-to-date as compared to HW. Reasonably accurate estimates of perinatal
      mortality rate can be made through record linkage.

PMID- 8979584
TI  - C-reactive protein as an indicator of complications in bacterial meningitis.
AB  - OBJECTIVE: To determine the value of serum C-reactive protein (CRP) estimation in
      the follow-up of bacterial meningitis (BM). DESIGN: Longitudinal follow-up.
      SETTING: Urban hospital. METHODS: Sequential serum CRP estimation was done in 50
      healthy children and in 100 children with BM. Serial serum CRP value was
      correlated with the clinical picture in BM. RESULTS: Serial serum CRP in 14
      patients with complicated BM was significantly different than the 72
      uncomplicated BM cases. CONCLUSIONS: Serial determination of serum CRP may be a
      cheap, simple and reliable prognostic indicator in BM.

PMID- 8979585
TI  - Outcome of dialysed patients with acute renal failure.

PMID- 8979586
TI  - Intussusception in older children.

PMID- 8979587
TI  - Granulocytic sarcoma in acute non-lymphocytic leukemia.

PMID- 8979588
TI  - Xeroderma pigmentosum.

PMID- 8979589
TI  - Age related changes in urinary 6-beta hydroxycortisol in normal infants.

PMID- 8979590
TI  - Disseminated melioidosis.

PMID- 8979591
TI  - Pulmonary veno-occlusive disease.

PMID- 8979592
TI  - Panic attack syndrome.

PMID- 8979593
TI  - Giant duodenal hematoma in hemophilia A.

PMID- 8979594
TI  - Congenital mesenchymal hamartoma of liver.

PMID- 8979595
TI  - Giant congenital nevocellular nevus and natal teeth.

PMID- 8979596
TI  - Choroid plexus carcinoma.

PMID- 8979597
TI  - Digital fracture polypectomy for juvenile rectal polyps is safe.

PMID- 8979598
TI  - Giardiasis and amebiasis in southern Iran.

PMID- 8979599
TI  - Conservative management of persistent pulmonary hypertension.

PMID- 8979600
TI  - Are these cases of heat stroke?

PMID- 8979601
TI  - Bacterial infections in leukemias.

PMID- 8979602
TI  - Furazolidone in uncomplicated enteric fever.

PMID- 8979604
TI  - Advances in the management of bronchial asthma.

PMID- 8979603
TI  - Neonatal Salmonella infection.

PMID- 8979605
TI  - Polyarteritis nodosa--a few unusual findings.
AB  - OBJECTIVE: To report the clinical spectrum of polyarteritis nodosa (PAN) from
      North India and highlight some unusual findings. DESIGN: Retrospective study.
      SETTING: Hospital based. SUBJECTS: Eight children with PAN. INTERVENTION:
      Treatment with prednisolone and cyclophosphamide. RESULTS: One child had
      spontaneous remission while another started deteriorating rapidly in spite of
      treatment and died within 2 weeks. Six children went into remission-of these one
      died, two were lost to follow-up and the remaining three are on regular follow-up
      for periods ranging from 3-5 years. CONCLUSIONS: Prednisolone and
      cyclophosphamide can significantly improve the outcome in childhood PAN.

PMID- 8979606
TI  - Value of CT scan in the diagnosis of meningitis.
AB  - OBJECTIVE: To study the diagnostic test characteristics of computed tomography
      (CT scan) in differentiating tuberculous (TBM) and pyogenic (PM) meningitis.
      DESIGN: Prospective diagnostic test evaluation. SETTING: Teaching hospital.
      METHODS: Children beyond 1 month of age admitted with meningitis were enrolled
      prospectively and CT scan done. Results of CT scan were compared with predefined
      gold standards for the diagnosis of either TBM or PM. RESULTS: CT scan was
      performed in 154 patients with meningitis. Of these 94 were TBM, 52 had PM and 8
      were indeterminate and excluded from analysis. Basal enhancement,
      ventriculomegaly, tuberculoma and infarction were all significantly more common
      in the TBM group, while subdural collections were seen more in the PM group. The
      highest sensitivity (89.2%) and specificity (100%) for diagnosis of TBM were
      found for basal enhancement or tuberculoma or both. CONCLUSIONS: CT scan can be
      used to effectively distinguish TBM and PM.

PMID- 8979607
TI  - Percentile curves for body-mass index of Punjabi infants.
AB  - OBJECTIVE: To study percentile distance growth pattern of Body Mass Index (BMI)
      of Punjabi male and female infants. DESIGN: Longitudinal. SETTING: Growth Clinic.
      SUBJECTS: 154 Punjabi infants (Male 86; Female 68), aged birth-12 months. FOLLOW
      UP: Nude body weight and crownheel length of all babies at birth and whereafter,
      were measured at monthly age intervals with time tolerance to +/-3 days by the
      same investigator upto 12 months of life. RESULTS: Mean (+/- SD) values for BMI
      measured 12.2 +/- 1.40 kg/m2 and 16.5 +/- 1.40 kg/m2 at birth and 12 months,
      respectively in male infants. The corresponding figures for female infants were
      12.5 +/- 1.60 kg/ m2 and 16.5 +/- 1.50 kg/m2. A rapid increase in BMI values
      amongst infants of both sexes between birth to about six months followed by
      flattening of curves upto 12 months of age indicates an age dependent nature of
      BMI during first half of infancy in comparison to latter half during which these
      demonstrated stable trend. These findings are in contrast to those of the western
      infants who showed a regular increase in BMI throughout the first year of life.
      Sex differences were not significant at majority of the age levels. CONCLUSIONS:
      Percentile grids presented for BMI represent a normal, healthy and well-nourished
      infant population which can be used to assess the adiposity status of infants of
      the two sexes during the first year of life.

PMID- 8979608
TI  - Breastfeeding practices in villages of central Karnataka.
AB  - OBJECTIVE: To asses the prevailing breastfeeding and infant feeding practices in
      rural areas. DESIGN: Stratified sampling method in a community based study.
      SUBJECTS: 1050 infants from 0-24 months of age. RESULTS: The timely first
      suckling rate was 0.3%. All the infants received prelacteal feeds. Colostrum was
      rejected by 29% of mothers. Delayed initiation of breastfeeding was common; 35%
      of babies were not breast-fed even at 48 h of birth. Exclusive breastfeeding was
      noted in 94% at 1 mo, 83.5% at 2 mo, 72.5% at 3 mo, 61.2% at 4 mo, 43.4% at 5 mo
      and 26.8% at 6 mo age. Timely complementary feeding rate was 57.3% among infants
      from 6 to 10 mo age. Continued breastfeeding rate was 99.7% at 1 year and 87.2%
      at 2 years. The bottle feeding rate was 49.4% among infants below 1 year age. The
      ever breast-fed rate was 97.0% and the median duration of breastfeeding was
      beyond 24 months. CONCLUSIONS: Bottle feeding is quite prevalent even in rural
      areas and the infant feeding practices are far from satisfactory.

PMID- 8979609
TI  - Training doctors for tomorrow.

PMID- 8979610
TI  - Not enough milk.

PMID- 8979612
TI  - Two different methods for feeding low birth weight babies.

PMID- 8979611
TI  - Amphotericin B in resistant visceral leishmaniasis.

PMID- 8979613
TI  - Congenital ocular malformations at birth.

PMID- 8979614
TI  - Anterior visual pathway tumors.

PMID- 8979615
TI  - Calcium gluconate--its unusual complication.

PMID- 8979616
TI  - Congenital candidiasis.

PMID- 8979617
TI  - Chorangioma of the placenta with hydrops fetalis.

PMID- 8979618
TI  - Lactose free diet.

PMID- 8979619
TI  - Is female infanticide spreading to Karnataka?

PMID- 8979620
TI  - Hypolipidemic effects of synthetic gugulsterones in normal rats and assessment of
      its long-term toxicity at cellular levels in various organs.
AB  - Synthetic gugulsterones when administered to rats for a period of 3 weeks in dose
      of 5.0 mg/kg body weight/day caused a reduction in levels of total cholesterol by
      30%, LDL-chol. by 40%, Tg by 40%. VLDL-chol. by 40% and HDL-chol. by 35%. The
      drug when administered to rats for a period of 16 weeks with increasing dose upto
      1150 mg/kg body weight/day, reduced VLDL-chol. and Tg. by 55% and 50%
      respectively (P < 0.001) and LDL-chol by 33% (P < 0.05), whereas HDL-chol. was
      increased by 25% (P < 0.001). Histopathological studies on liver, spleen,
      intestine, lung, kidney, stomach and adrenal gland revealed drug related changes
      in a few animals upon exposure to high dose of the drug.

PMID- 8979621
TI  - Hyperuricemia and pregnancy induced hypertension--reappraisal.
AB  - Serum uric acid estimation was done in forty primigravidae with pregnancy induced
      hypertension and twenty normotensive primigravida in the third trimester of
      pregnancy, at delivery and six weeks postpartum. The mean serum uric acid levels
      in normotensive women in the antenatal period and at delivery were 4.65 +/- 0.33
      and 4.88 +/- 0.23 mg% and in mild PIH were 5.42 +/- 0.55, 6.14 +/- 0.76 mg%,
      respectively. Level of serum uric acid in mild PIH was significantly higher than
      normotensive women (P). In severe PIH, the mean serum uric acid levels were 6.65
      +/- 0.60, 8.24 +/- 1.09 mg% in antepartum and at delivery respectively which was
      significantly more than control group and mild PIH group women (P). However, no
      differences was observed, in the serum uric levels between these groups during
      the postpartum period. Serum uric acid level of 5.5 mg or more was observed to be
      an indicator of PIH. Levels of serum uric acid did show a high positive
      correlation with the severity of PIH in relation to hypertension and proteinuria.
      Hyper uricemia (more than 5.5 mg% is associated with increased perinatal
      morbidity and mortality.

PMID- 8979622
TI  - Natural family planning--better prospect of contraception.
AB  - Natural Family Planning methods are based on naturally occurring signs of
      fertility by which a couple can prevent or achieve pregnancy. It requires good
      concept on signs of fertility in female and knowledge of human reproduction. For
      this reason, successful delivery delivery of NFP services is directly related to
      literacy rate among users.

PMID- 8979624
TI  - Pseudocysts of pancreas in children.
AB  - A total of 7 patients of pseudopancreatic cysts was managed in children over a
      period of 5 years Trauma was responsible for the development of pseudocyst in one
      while in rest of the patients no etiologic factor could be identified. All the
      patients underwent transgastric cystogastrostomy. With a mean follow-up of 30
      months, no death and no recurrence was found. It seems that surgical experience
      of pseudopancreatic cysts in children is similar to that seen in adults.

PMID- 8979623
TI  - Levels of glutamic acid decarboxylase (GAD), gamma amino butyric acid
      transaminase (GABA-T), glutamic acid dehydrogenase (GLDH) and proteins in
      cerebrospinal fluid of certain neurological disorders.
AB  - Important glutamic acid metabolising enzymes in brain namely GAD, GABA-A and GLDH
      have been studied in the CSF of tuberculous meningitis (TBM), pyogenic meningitis
      (PM) and brain tumor (BT). The levels of GAD were reported as picomoles of GABA
      formed/mg of protein/hour. The control levels of the enzymes were GAD = 129 +/-
      54, GABA-T = 533 +/- 146 and GLDH...O. 198 +/- 0.097. The levels of GAD were
      significantly increased (P < 0.001), in both TBM and PM, the values were 302 +/-
      81 and, 290 +/- 97 respectively. The GABA-T levels were significantly raised (P <
      0.001) only in PM cases 639 +/- 171. The values were reported as nano moles of
      GABA transformed/mg of protein/hour. The CSF-GLDH levels (unit/litre) showed
      significant elevation (P +/- 0.001) in TBM in PM, the values were 0.41 +/- 0.1
      and 0.41 +/- 0.18 respectively. The CSF proteins were markedly elevated in all
      the conditions.

PMID- 8979625
TI  - A study of computer aided medical diagnosis for internal medicine.

PMID- 8979627
TI  - Infant feeding practices in a tribal community of Melghat region in Maharashtra
      state.
AB  - 1. Out of 494 infants none was breastfed within 2 hours of delivery. 36% infants
      received first breastfeed after 24 hours of delivery 91.2% of the mothers used
      prelacteal feeds. 2. Only 31.06% of the infants were weaned, out of these only 7
      received complementary foods between 4-6 months. 3. Thus, it can be concluded
      that though breastfeeding is practiced by all mothers, there is need for early
      initiation of breastfeeding and proper weaning habits.

PMID- 8979626
TI  - Study on the effectiveness of enalapril as a monotherapy in mild to moderate
      hypertension.
AB  - This study highlights our experience with 53 patients with mild to moderate
      hypertension who had monotherapy with Enalapril, one of the newer Angiotensin
      Converting Enzyme inhibitors. Enalapril was found to be effective in controlling
      blood pressure in 41 patients (77%). In 12 patients (23%) addition of one more
      drug was necessary for control of hypertension. Side effects were noted in 9
      patients (17%). In two patients the adverse reactions were severe enough to
      warrant withdrawal of the drug.

PMID- 8979628
TI  - Role of mast cells in synovial diseases. A histopathological study.

PMID- 8979629
TI  - Current concepts in the immunology of allograft rejection.

PMID- 8979630
TI  - The effect of hematocrit on the efficiency of hemodialysis in cases of chronic
      renal failure.
AB  - Twenty patients of chronic renal failure were evaluated to study the effect of
      increase in hematocrit (Hct) on the efficiency of hemodialysis. All the patients
      were subjected to two hemodialysis of identical duration with an interdialytic
      interval of 48 hours. All were anemic with a mean hemoglobin of 6.73 gm% and a
      hematocrit of 22.2%. Hematocrit was raised to a mean of 32.02% following
      transfusion of 2 units (600-700 ml) of whole blood (p < 0.001) in the
      interdialytic interval. Blood clearances (Kb). Dialysate clearance (Kd),
      fractional decrement and Kt/V ratio of solutes (urea, creatinine and phosphates)
      were calculated during both the dialysis and compared with each other. Kt/V of
      urea decreased from 1.0589 +/- 0.24 to 0.89 +/- 0.15 (p < 0.001), and that of
      creatinine 1.003 +/- 0.19 to 0.832 +/- 0.009 (p < 0.001) and phosphates 0.992 +/-
      0.16 to 0.826 +/- 0.006 (p < 0.001) and it showed a negative correlation with
      rise in hematocrit. It was significant for creatinine and phosphates and
      insignificant for urea, suggesting thereby that the efficiency of dialysis
      decreased with increase in hematocrit. This is important in view of under
      dialysis in patients of normal or near normal hematocrit and suggests the need
      for modification of dialysis prescription in such situations.

PMID- 8979631
TI  - Food intake and nutrient adequacy of rural population of Guntur district (Andra
      Pradesh).
AB  - The study reported here was undertaken to investigate the food intake and
      nutrient adequacy of rural population in Guntur District of Andhra Pradesh. A
      total of 1200 pre-school children were covered under the study from three
      divisions of Guntur district of Andhra Pradesh. A 3 day dietary survey was
      conducted by a weighed method for estimating the food intake. Nutritional Value
      of the food consumed was calculated. Nutritional status was assessed by
      anthropometry. The consumption of milk was very inadequate. Most of the protein
      and energy were derived from cereals. It is also revealed that ascorbic acid and
      beta-carotene deficiency seem to be most predominant followed by riboflavin,
      thiamine, iron and niacin.

PMID- 8979632
TI  - Idiopathic thrombocytopenic purpura associated with Graves' disease--case report.

PMID- 8979633
TI  - Cancer control in the Asia Pacific region--the next lap.
AB  - Cancer control in any part of the world has to be a multi-directional effort
      addressed in a holistic manner. The general impression that cancer control means
      only collation of epidemiological data and efforts at primary prevention needs to
      be redefined because preventive and educative oncology, though an important
      component of cancer control, can achieve long-term goals only after 20 years or
      more. Along with such long-term objectives, methodology needs to be developed
      which takes care of immediate and recent needs in early diagnosis, effective
      treatment, and appropriate basic research for the ultimate control and cure of
      cancer. A holistic approach to the cancer control effort will, therefore, need
      the combined skills of many different specialists.

PMID- 8979634
TI  - Prize the seed.

PMID- 8979635
TI  - Beware of complacency about tuberculosis and other communicable diseases.

PMID- 8979636
TI  - The gateclosing of the American health care system.

PMID- 8979637
TI  - Old wine in new bottles--nursing in the 21st century.

PMID- 8979638
TI  - Utilization of an academic nursing center.
AB  - Academic nursing centers, or nurse-managed clinics, are relatively new health
      care delivery systems. Little information exists as to the demographic
      characteristics of individuals who use academic nursing centers for health care.
      Moreover, little is found in the literature about the types of conditions
      diagnosed and the procedures and tests performed at academic nursing centers.
      Based on one academic nursing center, this project showed that 3,263 persons
      received care during an 8-month period. The types of conditions diagnosed and the
      demographic characteristics of individuals cared for are described. The
      procedures and diagnostic tests performed are identified. These data have
      important implications for marketing, predicting resources, and meeting the
      educational component of the academic nursing center.

PMID- 8979639
TI  - Elements of a nursing professional practice model.
AB  - The authors define a professional practice model (PPM) as a system (structure,
      process, and values) that supports registered nurse control over the delivery of
      nursing care and the environment in which care is delivered. A PPM has five
      subsystems: values, professional relationships, a patient care delivery model, a
      management approach, and compensation and rewards. Analysis of five PPMs
      described in the literature showed that the professional values addressed most
      often are nurse autonomy, nurse accountability, professional development, and
      emphasis on high-quality care. Teamwork, collaboration, and consultation
      consistently appeared as approaches to enhance professional relationships.
      Primary nursing and case management are the care delivery systems most often used
      in the models. Decentralizing decision making, expanding the scope and type of
      unit nurse manager responsibilities, and instituting structural changes to
      support professional practice were common activities in the management subsystem.
      Compensation and reward systems generally recognized professional achievement and
      contribution toward organizational goals. Recommendations for implementing and
      evaluating PPMs are offered.

PMID- 8979640
TI  - Partnership for a nurse practitioner-directed student health primary care center.
AB  - Since 1991, the George Mason University Student Health Center (SHC) has been a
      primary health care center directed by College of Nursing and Health Science
      (CNHS) nurse practitioner (NP) faculty. This model was planned and implemented
      through a partnership between the CNHS and Student Services. From September 1991
      until the present, the number of student visits has more than doubled, and the
      offered services have tripled without a comparable increase in budget and with
      minimal expansion of space. The student population now has access to
      comprehensive quality primary care services on-site at a relatively small
      investment per student. The focus of care goes beyond simply managing current
      health care needs by emphasizing prevention of future health problems, wellness,
      and quality of life. In addition, negotiations with surrounding specialists have
      resulted in a prompt and cost-effective referral system as needed by conditions
      exceeding the capabilities of the SHC providers. Responses to student surveys
      regarding the quality, availability, and cost of care, as well as the process
      involved in receiving that care, indicate the highest level of satisfaction among
      students using these services. The CNHS has a fertile, convenient faculty
      practice site as well as several clinical placements for NP as well as
      undergraduate students. This NP faculty-directed SHC offers a cost-effective,
      consumer-responsive alternative for delivering primary care services to the
      members of the university community.

PMID- 8979641
TI  - Relationships among childhood parental care, professional school climate, and
      nursing student caring ability.
AB  - A mailed random-sample survey of 350 senior baccalaureate nursing students
      explored relationships among early maternal and paternal care, the caring climate
      of nursing schools, and caring ability. Caring ability was quantified with the
      Caring Ability Inventory, Maternal and paternal care were measured with the
      Parental Bonding Instrument. School climate was measured on the Charles F.
      Kettering School Climate Inventory. There is no linear correlation between level
      of maternal or paternal care and subsequent caring ability (r = .01 and 0.01,
      respectively). However, a curvilinear relationship exists: Those with higher
      caring are respondents who scored both at the highest and the lowest levels of
      maternal care. Moreover, levels of caring within nursing schools appear to
      moderate caring ability developed at home. A caring school climate is the
      strongest predictor of caring ability (r = 0.16, P < .01). Thus, it is of concern
      to note that only 52 per cent of the respondents rated their schools high in
      caring. Caring is a valued attribute in professional nursing. If this quality is
      to flourish, it must be cultivated within the climate of nursing schools that
      exert a major professional socializing influence on future nurses.

PMID- 8979642
TI  - Rethinking race and attrition in nursing programs: a hermeneutic inquiry.
AB  - This hermeneutic study examined the lived experience of four self-identified
      African-American students enrolled in predominantly white baccalaureate nursing
      programs. An understanding of the following concerns was sought: (1) Does being
      black matter in an educational program that is predominantly white? (2) Does
      being black in a predominantly white nursing program hinder a student's ability
      or desire to continue toward his or her educational goal? These concerns were
      guided by the major research question: What is the meaning of being black in a
      predominantly white nursing program? Critical hermeneutic inquiry, as explicated
      by Jurgen Habermas, was used as the philosophical framework. Audiotaped
      interviews were transcribed and subsequently analyzed by a team of researchers.
      Three constitutive patterns emerged from the analysis of the texts: Being
      Different/Being the Same, Student As Teacher: Toward a Surrogate Pedagogy, and
      Resoluteness: I'll See You at Graduation. Findings suggest that empirical
      research concerning the attrition of blacks from predominantly white nursing
      programs must include a description of what it means to be black or different in
      these settings.

PMID- 8979643
TI  - Theoretical and practical considerations in investigating motivation and
      discomfort during prolonged exercise.
AB  - In this article a motivational perspective to exercise and sport are reviewed.
      The review emphasises the social-cognitive approach that has recently been
      utilised extensively in the sport psychology literature. The review concentrates
      on the goal perspective approach to achievement motivation, the concept of
      competitiveness in sport, and the psychological constructs of perceived
      competence, efficacy, and control in association with the environmental
      conditions under which performance is evaluated. An integrated model of
      motivation is postulated to better account for motor/physical performance. The
      model is used later to show how performance can be examined in emotionally (i.e.,
      frustration) and physically (work hard) demanding situations that can be
      manipulated and standardised. Experimental Support for the model is provided.

PMID- 8979644
TI  - Effect of time of day on aerobic power in exhaustive high-intensity exercise.
AB  - The purpose of this study was to determine if there is an effect of time of day
      on aerobic power elicited during exhaustive high-intensity constant-power cycle
      ergometer exercise. Twenty-four college students (12 women and 12 men) each
      performed three exhaustive exercise tests (against 3.5 W.kg-1 for women and 4.0
      K.kg-1 for men). The first test served as a learning trial. The second and third
      tests were scheduled at about 08:00 hrs (AM) and 16:00 hrs (PM) with the order of
      testing randomly assigned. Results from these two tests were compared for
      evidence of a time of day effect using a two-way ANOVA with repeated measures
      over time of day and with subjects nested in sex. Time to exhaustion was 9%
      greater (p < 0.01) in the PM (214 +/- 43 sec) than in the AM (196 +/- 38 sec).
      Peak VO2 was 7% higher (p < 0.01) in the PM (3.34 +/- 1.00 1.min-1) in the AM
      (3.11 +/- 0.98 1.min-1). The aerobic system responded 6% faster (p = 0.04) in the
      PM than in the AM: the time constant describing VO2 kinetics was 33.5 +/- 5.7 sec
      in the PM and 35.5 +/- 5.5 sec in the AM. However, there were no significant
      correlations (p > or = 0.20) between the AM-PM differences in time to exhaustion,
      time constant of the response, or peak VO2. The findings confirm previous reports
      of a time of day effect on time to exhaustion in high-intensity exercise. It was
      also concluded that there is a higher peak VO2 in the PM than in the AM. In
      addition, there is a time of day effect on VO2 kinetics, with the aerobic system
      responding faster in the PM than in the AM.

PMID- 8979645
TI  - Aerobic power and supramaximal endurance of competitive figure skaters.
AB  - OBJECTIVE:  HYPOTHESES: 1) figure skaters possess average aerobic power; 2) on
      ice training would not improve aerobic power of supramaximal endurance; 3) off
      ice training plus on-ice training would improve aerobic power and supramaximal
      endurance. EXPERIMENTAL DESIGN: This was a prospective, controlled study in which
      we monitored ice skaters before, during and after two different 10 week training
      programs. SETTING: Athletes training for competition sanctioned by the United
      States Figure Skating Association. PARTICIPANTS: 15 figure skaters (12 females)
      enrolled at an ice skating academy were randomly placed in two study groups.
      INTERVENTIONS: Grp 1 maintained on-ice training and Grp 2 supplemented on-ice
      with cycle ergometer training. MEASURES: Maximum O2 consumption (VO2peak) during
      cycle ergometer exercise, anaerobic threshold, HR, supramaximal exercise time and
      the lactate (LACT) response to exercise. RESULTS: (*, p < 0.05), Grp 1: VO2peak,
      pre = 44.2 +/- 2.2 ml/[kg.min], post = 41.4 +/- 1.6 ml/[kg.min]; VO2peak% (%
      predicted), pre = 100 +/- 5%, post = 92 +/- 4%; anaerobic threshold as % VO2peak
      (AT%), pre = 74 +/- 3%, post = 73 +/- 3%; Supramaximal Time, pre = 0.87 +/- 0.12
      min, post = 0.94 +/- 0.12 min; lower LACT occurred at VO2peak and supramaximal
      exercise following on-ice training. Grp 2: VO2peak, pre = 50.7 +/- 3.6
      ml/[kg.min], post = 55.9 +/- 3.3 ml/[kg.min]*; VO2peak%, pre = 110 +/- 7%, post =
      121 +/- 6%*; AT%, pre = 80 +/- 2%, post = 83 +/- 2%*; Supramaximal Time, pre =
      1.31 +/- 0.18 min, post = 2.69 +/- 0.66 min*; lower LACT occurred at 50%, 75% and
      VO2peak following training. CONCLUSIONS: 1) Grp 1 plus Grp 2 had average aerobic
      power (VO2peak = 105 +/- 3% of predicted) prior to the study; 2) on-ice training
      did not affect aerobic power or supramaximal endurance, while off-ice training
      improved these parameters; 3) the LACT response detected training adaptations.

PMID- 8979646
TI  - The assessment of human dynamic muscular function: a comparison of isoinertial
      and isokinetic tests.
AB  - This investigation compared the relationship of isokinetic and isoinertial tests
      of muscular function to dynamic upper body performances. The electromiyographic
      activity of each of the tests of muscular function, as recorded by surface
      electrodes, were examined to determine whether neural differences underlie the
      ability of the test to relate to performance. Twenty four subjects performed
      isokinetic and isoinertial tests of muscular function in a bench press movement.
      The isokinetic tests were performed at velocities of 60, 90 and 120 deg/s while
      the isoinertial tests were performed at loads of 30%, 60% and 130% of the one
      repetition maximum. Subjects also performed the following tests of dynamic
      performance: a maximum one repetition bench press (1 RM), a seated shotput throw
      and two drop bench press throws from a height of 0.25 m at various loads.
      Forces/torques, displacement and electromyographic data were recorded from the
      isoinertial and isokinetic tests. Both the isoinertial and isokinetic parameters
      were related to the various measures of upper body performance (r = 0.33-0.94),
      however, neither was superior at predicting performance. Further, the
      relationship between the tests of muscular function were consistently high (r =
      0.75-0.88). This was the case, even though the magnitude of the EMG signals were
      significantly higher in the isoinertial, as compared to the isokinetic tests. It
      is postulated that structural considerations, such as a specific testing
      position, rather than neural factors, underlie the observed results. These
      results support previous research which has reported the existence of a
      generality of strength across dynamic testing modalities.

PMID- 8979647
TI  - Physiological profile of age-group wrestlers.
AB  - This research compares the physiological characteristics of young wrestlers
      grouped by age. Three hundred and twenty eight wrestlers (mean age 15.99 +/- 1.08
      years and mean weight 65.94 +/- 11.01 kg) attending a wrestling training camp
      between 1990 and 1994 were tested to determine their physiological capacities.
      The physiological profile included body weight, body composition measured by
      hydrostatic weighing, sum of skinfolds, aerobic power, grip strength, absolute
      and relative endurance, situps, pushups, fatigue, and flexibility measures.
      Wrestlers were divided into three age categories: G1: < or = 15 years of age; G2:
      16 years of age; and G3: > or = 17 years of age. Analysis of variance with Tukey
      post hoc test revealed statistically significant (p < 0.05) differences in body
      weight (G1 < G2,G3), fat free weight (G1 < G2,G3), grip strength (G1 < G2,G3),
      absolute (G1 < G2,G3; G2 < G3) and relative endurance (G1 < G3,G2 < G3), pushups
      (G1 < G3; G2 < G3), sit and reach (G1 < G3), Margaria-Kalamen power (G1 < G2,G3),
      and Wingate arm and leg mean powers (G1 < G2,G3). When covaried for body weight
      and fat free weight, there were no significant differences in grip strength and
      Margaria-Kalamen power. Significant differences in arm mean power when covaried
      for body weight and fat free weight (G1 < G3) and for leg mean power when
      covaried for body weight (G1 < G3) were noted. These wrestlers were similar to
      young wrestlers in published research, with low body fat, excellent aerobic
      capacity and flexibility. When separated by age, the younger wrestlers possess
      less body weight, fat free weight, grip length, and power measures, possibly due
      to lower muscle mass.

PMID- 8979648
TI  - Effects of enhanced physical education on lung volumes of primary school
      children.
AB  - OBJECTIVE: To test the impact of an enhanced physical education programme upon
      the growth and development of static and dynamic lung volumes of primary
      schoolchildren. EXPERIMENTAL DESIGN: Quasi-experimental three factor design
      (treatment x gender x urban vs rural environment) with students evaluated over
      each of 6 years of primary school. SETTING: Entire classes from State schools in
      urban and rural environment. PARTICIPANTS: All willing students aged 7-12 years
      in selected classes; initially 546 students, with 4% drop-out rate per year.
      INTERVENTION: Five hours of additional physical education per week, taught by
      specialist. MEASURES: Body dimension (height, body mass), aerobic power
      (treadmill to exhaustion), forced vital capacity (FVC), one second forced
      expiratory volume (FEV1.0). RESULTS: Small but statistically significant
      influences of treatment, gender (M > F) and environment (rural > urban) which
      could not be explained by body size. Both FVC and FEV1.0 conform closely to cubic
      functions of height in metres: Boys FVC = 0.93 (H)3, FEV1.0 = 0.79 (H)3. Girls
      FVC +/- 0.85 (H)3, FEV1.0 = 0.76 (H)3. CONCLUSIONS: A regular physical education
      programme can enhance lung volumes in primary school students. Norms should allow
      for gender differences, and reflect the potential attainment of students
      receiving adequate physical training and living in an area of low air pollution.

PMID- 8979649
TI  - Improvement in exercise tolerance and spirometric values in stable chronic
      obstructive pulmonary disease patients after an individualized outpatient
      rehabilitation programme.
AB  - OBJECTIVE: We sought to determine whether patients with stable chronic
      obstructive pulmonary disease (COPD) whose exercise performance is mainly limited
      by dyspnoea are able to improve their exercise tolerance after rehabilitation
      with an individualized programme based on aerobic training at the ventilatory
      threshold (VT) level. PATIENTS AND EXPERIMENTAL DESIGN: Thirteen stable and
      moderate to severe COPD patients took part in an outpatient rehabilitation
      programme lasting 4 months. This individualized programme consisted of exercise
      training (general training on cycle and upper-limb training by rowing at the
      heart rate corresponding to VT) together with provision of adequate calorie and
      protein support. RESULTS: Lung function test after rehabilitation revealed
      significant increases in FVC (82.9 vs 69.2 % pred) and FEV1 (47.2 vs 39.7 %
      pred), although FEV1/FVC were unchanged (44.8 vs 46.8%). Incremental exercise
      test performed on cycle revealed significant increases in time, work rate (82.0
      vs 63.2 W), peak VO2 (14.6 vs 10.7 ml.kg-1.min-1), peak VO2 (840 vs 701 ml.min
      1), peak VT (1309 vs 980 ml), and O2-pulse (8.3 vs 6.7). However, exercise tests
      were always symptom-limited by dyspnoea. CONCLUSIONS: We conclude that this
      individualized outpatient rehabilitation programme is able to improve exercise
      tolerance in stab le COPD patients affected by dyspnoea during exercise, through
      an apparent reconditioning of both skeletal and respiratory muscles and improved
      gas exchange during exercise, thus reducing the ratio of dead space to tidal
      volume. In consequence, patients whose exercise capacity is so reduced that they
      cannot develop significant lactic acidosis may reduce the ventilatory cost for
      exercise through this individualized therapy.

PMID- 8979651
TI  - Lipoprotein profile, diet and body composition in athletes practicing mixed an
      anaerobic activities.
AB  - OBJECTIVE: To compare lipoprotein profile, body composition and diet in a sample
      of athletes practicing mixed and anaerobic sports activities, and in a group of
      sedentary controls. EXPERIMENTAL DESIGN: Cross selectional study. PARTICIPANTS:
      Twenty professional soccer players (mixed trained), twenty body builders
      (anaerobic trained) and twenty sedentary subjects, all males and matched for age
      were studied. RESULTS: No significant differences in total serum cholesterol,
      triglycerides, HDL-C, LDL-C, apolipoprotein A-I, A-II, B, C-II, C-III, and E
      levels were found when the three groups were compared. Bioelectrical impendance
      analysis disclosed significantly lower body fat percentages in both groups of
      athletes, and increased fat free mass only in body builders. Daily calorie intake
      was higher, and alcohol intake was lower in the athletes, compared with controls.
      Body builders had lower carbohydrate, and higher protein and cholesterol intakes,
      while soccer players had a lower polyunsaturated to saturated fat ratio. None of
      the apolipoproteins examined was correlated with any body composition of diet
      parameters. No correlations between lipid parameters and anthropometric or
      dietary variables were found by multivariate analysis when the subjects were
      considered as a whole. CONCLUSIONS: Our data suggest that in healthy lean
      normolipemic males, the lipoprotein profile is not modified by mixed or anaerobic
      sport activities and the respective modifications in body composition and diet.

PMID- 8979652
TI  - Telemark skiing injuries.
AB  - Telemark skiing has become increasingly popular over the past 5 years. Telemark
      skiing poses unique risks when compared to alpine skiing, because of different
      equipment, technique, and varied skiing environments. A retrospective survey of
      telemark skiers was conducted in Western Washington in 1994 to obtain skier
      information on ski habits, demographics, frequency and types of injury, and
      equipment used at time of injury. During the 5 month survey period, 118 (63%) of
      187 surveys distributed at 7 sites were returned. The overall injury rate was
      comparable to alpine skiing injury rates at 10.7/1000 skier days. Less
      experienced skiers and women had higher injury rates, 20/1000 and 13.1/1000 skier
      days, respectively. The predominant injury sites were knee (41%), hip (13%), and
      thumb (8%). The knee injuries sustained by telemark skiers appear to be less
      severe than alpine skiers, with less duration of disability and lower surgical
      rates. An association was found between the use of plastic reinforced boots and
      significant ligamentous knee injuries when compared to skiers with leather boots
      (p < 0.01, chi 2 = 5.43).

PMID- 8979650
TI  - Postprandial lipemia in obese men with abdominal fat patterning.
AB  - OBJECTIVE: The purpose of this study was to assess differences in measures of
      postprandial triglyceride (TG) clearance between obese men with abdominal fat
      patterning (OAF) and men of desirable weight (DW). It was hypothesized that the
      OAF men would have impaired postprandial TG clearance. EXPERIMENTAL DESIGN: A
      comparative design was used. SETTING: Data were collected in a research
      laboratory with access to blood analysis instrumentation. PARTICIPANTS: Fourteen
      healthy, physically active, normolipemic men (7 OAF and 7 DW) were studied.
      INTERVENTIONS: Each subject consumed an oral fat load (78 grams of fat) and blood
      samples were collected every hour for 8 hours. MEASURES: Measures of postprandial
      lipemia included: incremental TG area, total TG area, time to peak TG
      concentration, maximal change in TG concentration, and time to return to baseline
      TG concentration. RESULTS: OAF men had significantly greater total area under the
      TG curve (24.7 +/- 1.09 vs 16.1 +/- 1.3 mmol-L(-1).8 hours, p = 0.003) and
      greater maximum TG change (2.0 +/- 0.3 vs 1.2 +/- 0.2 mmol-L-1, p = 0.03)
      following the oral fat load. Additionally, the total area under the TG curve was
      positively correlated with baseline TG concentrations (r = 0.53) and inversely
      correlated with baseline HDL2 concentrations (r = 0.64). Baseline HDL2
      concentrations were inversely correlated with time to return to TG baseline (r =
      0.57). CONCLUSIONS: Normal fasting lipoprotein profiles and regular physical
      activity do not preclude OAF men from having pronounced postprandial lipemia.

PMID- 8979653
TI  - Asphyxial death of a young skier.
AB  - OBJECTIVE: Review of the cause of death in fatal downhill skiing accidents is
      important to prevention: this report concerns a boy found dead with his head
      buried in powder snow. EXPERIMENTAL DESIGN: Case history of an 11-year-old boy
      who was found dead 4 hours following descent of a steep ski slope. SETTING:
      Treatment by mountain rescue team and hospital emergency room. PATIENT: A boy who
      was discovered immersed head first in one meter of powder snow, with no sign of
      an avalanche or struggling, and no vital signs. The differential diagnosis
      included concussion + asphyxia, cervical injury, loss of consciousness from other
      causes, and hypothermia. INTERVENTIONS: Standard cardio-pulmonary resuscitation,
      rewarming by bladder irrigation and extracorporeal circulation. RESULTS: The
      rectal temperature, initially 29.4 degrees C, fell further to 23.3 degrees C
      during evacuation in a heated ambulance. On hospital admission, a blood sample
      showed creatine kinase 5306 units, K+ 16 mM, pH 6.38, PaCO2 223 Torr, and PaO2 67
      Torr. There was no ECG rhythm, and radiography revealed pulmonary edema but no
      cervical malignment. Emergency measures normalized blood gases, but did not
      restore cardiac action. CONCLUSIONS: Death was caused by asphyxia, secondary to
      mild concussion. The public needs education on the dangers of deep powder snow.
      Adventurous skiers should wear helmets, and should not ski alone on steep
      mountainsides.

PMID- 8979654
TI  - Three rules of thumb.

PMID- 8979655
TI  - A special anniversary.

PMID- 8979656
TI  - New drug therapies for glaucoma.

PMID- 8979657
TI  - The effect of a medication alarm device on patient compliance with topical
      pilocarpine.
AB  - BACKGROUND: This study was performed to investigate the use of an electronic
      medication alarm device (Prescript TimeCap) to enhance compliance in glaucoma
      patients taking pilocarpine. METHODS: Thirteen subjects were selected who had
      been diagnosed with open-angle glaucoma and were receiving 1 drop of pilocarpine
      solution 4 times a day in both eyes. For each subject, the study was divided into
      2 30-day phases, one with the medication alarm device and the other without.
      Thus, each subject served as his or her own control. Compliance was measured
      based on the amount of pilocarpine used and by patient questionnaire. In
      addition, the subjects completed a post-study questionnaire regarding the ease of
      use of the TimeCap and whether it helped them remember to take their medication.
      RESULTS: When subjects used the TimeCap, they administered an average of 2.867 g
      (P < 0.0001) more pilocarpine over the 30 days than during the period without it.
      Subjects also estimated a significant difference in compliance level, 95.8
      percent with the alarm device versus 83.1 percent without it (p < 0.01). All
      subjects reported no difficulty using the TimeCap, and all reported that it
      helped them remember to take their medication. CONCLUSIONS: These results are
      highly suggestive that the TimeCap is an effective compliance aid for glaucoma
      patients on pilocarpine.

PMID- 8979658
TI  - Ocular tolerability of timolol in Gelrite in young glaucoma patients.
AB  - BACKGROUND: Although initial patient response to timolol maleate in Gelrite
      (Timoptic XE) has been generally favorable in clinical settings, anecdotal
      reports of blurred vision warrant further investigation comparing the
      tolerability of this new formulation with that of timolol maleate in conventional
      solution. METHODS: A prospective, double-masked, randomized, cross-over study was
      performed using 28 normal volunteers who had no evidence of ocular disease,
      including glaucoma. Mean subject age was 32.5 years. Subjects were randomized to
      receive one drop in each eye of either timolol maleate in solution (TS) 0.5
      percent or timolol maleate in Gelrite (TXE) 0.5 percent. Subjects rated each
      medication, using a visual analog scale, at the following time intervals: prior
      to drug instillation, immediately following instillation, 1 min, and at 15 min,
      30 min, 1 hour, 2 hours, and 4 hours. RESULTS: Wilcoxon Matched Paris Test showed
      statistically significant differences at 1 minute for tearing (p = 0.003),
      blurred vision (p = 0.001) and drug acceptance (p = 0.028) in favor of TS. At 15
      minutes and thereafter, however, none of the differences between groups was
      significant. Visual acuities were unaffected by either TS or TXE. CONCLUSIONS:
      These data suggest that TXE may impair visual function more than TS, but these
      effects are briefly and transitory. TXE appears to be a clinically acceptable
      drug delivery vehicle for use during the young glaucoma patient's waking hours.

PMID- 8979659
TI  - Efficacy of silicone punctal plugs as adjuncts to topical pharmacotherapy of
      glaucoma--a pilot study. Punctal Plugs in Glaucoma Study Group.
AB  - BACKGROUND: The concept of enhancing the ocular hypotensive effects of topical
      antiglaucoma medications by impeding lacrimal drainage of medication has been
      insufficiently studied. This investigation sought to evaluate the effect of
      bilateral inferior punctal occlusion using silicone punctal plugs on the ocular
      hypotensive effect of topically applied timolol. METHODS: A randomized, double
      masked, cross-over clinical trial was conducted, comparing the ocular hypotensive
      effect of timolol maleate 0.25 percent, both with and without occlusion of the
      inferior punctum with the Freeman silicone punctal plug. Following a 2-week
      washout of topical medication, 17 subjects with early primary open-angle glaucoma
      or ocular hypertension received one drop of timolol 0.25 percent in each eye with
      or without punctal plugs in place. Blood pressure, resting pulse rate, and
      intraocular pressure were measured both before timolol instillation and at
      intervals of 1, 2, 4, 8, and 12 hours following drop instillation. Following a 2
      week washout period, the subjects were evaluated with the alternative treatment.
      RESULTS: There was no statistically significant difference (p = 0.648) in IOP
      levels between treatment groups. CONCLUSIONS: This pilot suggests that need for a
      longer-term study with larger numbers of subjects to evaluate the potential role
      of silicone punctal plugs to enhance the ocular bioavailability of topically
      applied antiglaucoma medications.

PMID- 8979660
TI  - Pupillary dilation and funduscopy with 1.0% hydroxyamphetamine plus 0.25%
      tropicamide (Paremyd) versus tropicamide (0.5 or 1.0%) as a function of iris and
      skin pigmentation, and age.
AB  - BACKGROUND: This study was designed to evaluate the effect of Paremyd, a
      combination of 1.0 percent hydroxyamphetamine hydrobromide and 0.25 percent
      tropicamide, on pupil size during binocular indirect ophthalmoscopy (BIO) upon
      164 subjects of various skin pigmentation, iris color, and age. METHODS:
      Pupillary dilation and ease of performing BIO were measured after 30 minutes
      following instillation of a single drop of either Paremyd or tropicamide (1.0 or
      0.5 percent) to an eye. Subjects were assigned to one of three groups; either
      Paremyd OU, or Paremyd OS and tropicamide (either 0.5 or 1.0 percent) OD, or
      Paremyd OD and tropicamide OS. Pupillary dilation was measured during BIO
      performed at a set illumination using a near point card. RESULTS: Results
      indicate that Paremyd is a significantly more effective dilator than either
      concentration of tropicamide alone. BIO was rated good to excellent for all
      dilating agents. As could be expected (based upon data from previous
      experiments), there was a small, but significant, negative correlation between
      dilation and age, skin pigmentation, and iris pigmentation. CONCLUSIONS: Paremyd,
      because of its superior effect upon dilation without side effects, can be the
      preferred agent used for routine single-drop dilation in all patients,
      independent of age, iris color, or skin color.

PMID- 8979661
TI  - Survival of contaminating bacteria in over-the-counter artificial tears.
AB  - BACKGROUND: The use of OTC artificial tears is becoming increasingly widespread.
      Unintentional contamination of artificial tear products potentiates a risk of
      developing bacterial keratitis or exacerbating an existing eye infection.
      Presently, no published study has investigated recovery from bacterial
      contamination of artificial tear products. METHODS: Four different over-the
      counter (OTC) artificial tear products were contaminated with two types of
      bacteria. Staphylococcus aureus and pseudomonas aeruginosa were analyzed for the
      survivability of the microorganisms at various times following contamination.
      RESULTS: In this cross-sectional study, it was found that all the preserved
      brands showed a significant recovery rate from contamination compared to the
      preservative-free brand. After 9 hours, the preservative-free brand did not
      completely regain sterility after contamination with either bacteria.
      CONCLUSIONS: This study indicates that preserved artificial tears recover from
      bacterial contamination at a significantly faster rate than preservative-free
      products. It is likely that the recovery from bacterial contamination is not
      solely attributed to the preservative, but that other variables may contribute.

PMID- 8979662
TI  - Comparison of efficacy and tolerance between 1% hydroxyamphetamine plus 0.25%
      tropicamide (Paremyd) and 0.5% tropicamide combined with 2.5% phenylephrine.
AB  - BACKGROUND: Paremyd, consisting of a combination of 1.0 percent
      hydroxyamphetamine and 0.25 percent tropicamide, is a commercially available
      eyedrop used clinically for diagnostic mydriasis. This study sought to determine
      if one drop of Paremyd is equally effective and tolerable as the traditional
      combination of one drop each of 2.5 percent phenylephrine and 0.5 percent
      tropicamide. METHODS: A prospective, double-masked, randomized, cross-over study
      was conducted in 60 normal volunteers ranging from age 20 to 35 years (mean 24.3
      years). Twenty-two subjects (36.7 percent) were male, and 32 subjects (53.3
      percent) had brown irides. Pupil diameter, amplitude of accommodation, distance
      and near visual acuity, and subjective comfort of eyedrop instillation were
      assessed for 8 hours following drug instillation. RESULTS: Significantly more
      subjects (p < 0.05) experienced adverse ocular symptoms with the tropicamide plus
      phenylephrine (TP) combination than with Paremyd (P). There was no statistically
      significant (p > 0.05) difference in mydriatic response between TP and P. During
      the first hour, however, TP and P demonstrated significant (p = 0.001)
      differences in cycloplegic effect. CONCLUSIONS: Paremyd appears to be as
      effective a mydriatic as TP, but with greater comfort on instillation. Paremyd
      has less effect on accommodation.

PMID- 8979663
TI  - Canthaxanthine retinopathy.
AB  - BACKGROUND: A 42-year-old white female complaining of decreased vision was
      examined and small golden particles were found in the macular regions of both
      eyes. It was ascertained that the patient had been using an oral bronzing agent,
      canthaxanthine (Orobronze), for the previous 10 years. METHODS: The method of
      deposition of these crystalline particles and their possible sequela are
      presented. The differential diagnosis of this condition is also described.
      RESULTS: In this case a crystalline retinopathy was induced by the oral ingestion
      of a bronzing agent. CONCLUSIONS: Although the gold-like particles have no visual
      consequences, it is important for the clinician and the patient to be aware of
      their etiology.

PMID- 8979664
TI  - Uveitis associated with rifabutin therapy: a clinical alert.
AB  - BACKGROUND: The incidence of Mycobacterium avium complex (MAC) infection is
      increasing among patients with AIDS. Rifabutin therapy has been demonstrated to
      be effective in the treatment and prophylaxis of MAC infection. over the past 3
      years there have been several reports of uveitis associated with rifabutin
      therapy. The uveitis is almost always interior, begins unilaterally and
      progresses to involve both eyes. There is almost always a hypopyon present, and
      the uveitis progresses aggressively. It responds well to conventional treatment
      along with the discontinuance of rifabutin. METHODS/RESULTS: This paper presents
      a new case of rifabutin uveitis and a review of the various published reports to
      date. CONCLUSIONS: All primary eye care clinicians should be aware of this new
      and unique clinical presentation and be prepared to recognize it quickly and
      treat it appropriately.

PMID- 8979665
TI  - The continuing impact of treatment of eye disease on optometric practice in
      Missouri.
AB  - BACKGROUND: This study is a follow-up to a study performed in 1991 to determine
      the continuing impact of the use by optometrists in Missouri of therapeutic
      agents (TPA) to treat eye diseases. METHODS: Sixty-four percent of the Missouri
      optometrists certified to use therapeutic pharmaceutical agents responded to a
      1995 questionnaire. RESULTS: More than 90 percent of those responding prescribe
      all categories of topical agents, while oral agents are used at lower
      percentages. Almost two-thirds of optometrists are registered with the Drug
      Enforcement Administration to prescribe controlled substances. The median number
      of therapeutic prescriptions written per year was 240, an increase of 67 percent
      from the previous study. More than half of the respondents now receive in-office
      detailing by drug company representatives. A small percent of optometrists have
      hospital clinical privileges and about one-fourth have privileges in nursing
      homes. CONCLUSIONS: The percentage of TPA-certified optometrists residing and
      practicing in Missouri has risen from one-half to slightly more than three
      fourths of practitioners in a 4-year time period. This increase, coupled with the
      demonstrated increase in therapeutic prescriptions written, enhanced exposure to
      in-office detailing, and recent amendment of the optometry law to include the
      management of glaucoma bodes well for the delivery of primary eye care to
      citizens of the state.

PMID- 8979666
TI  - Osteopathic medical education at the bridge to the 21st century.

PMID- 8979667
TI  - History of osteopathic medical education accreditation.

PMID- 8979668
TI  - Undergraduate osteopathic medical education.

PMID- 8979669
TI  - Income and expenditures of osteopathic medical colleges.

PMID- 8979670
TI  - Osteopathic graduate medical education.

PMID- 8979671
TI  - Certification of osteopathic physicians.

PMID- 8979672
TI  - Research programs of the AOA and their role in osteopathic medical education.

PMID- 8979673
TI  - AOA continuing medical education.

PMID- 8979674
TI  - In pursuit of generalism: basic factors influencing the specialty decisions of
      osteopathic medical school seniors in 1995.
AB  - An analysis of survey responses of seniors graduating from osteopathic medical
      school in 1995 shows that the selection of the medical specialty they planned to
      pursue in their postgraduate training was considerably influenced by 10 common
      factors. These factors ranged from the students' orientation to people or
      techniques, to prestige and income associated with the specialty. The People
      orientation factor exerted a strong influence on students planning to pursue
      primary care specialties (defined as Family Practice, General Internal Medicine,
      and General Pediatrics) Similarly, for students planning to pursue a nonprimary
      care specialty, the Prestige/income, the Intellectual Content factor, and the
      Research Factor, with its absence of stress and opportunity for research in other
      nonprimary care fields, swayed their decision. These findings have implications
      for the medical school admissions process. If that process can be used to
      identify students who relate well to people and are more oriented to dealing with
      preventive medicine and the broad spectrum of health problems presented by
      individual patients, then it could become an even greater force in the movement
      toward generalism in medicine.

PMID- 8979675
TI  - Geriatric education in osteopathic medical schools.
AB  - To determine if the curricula at the colleges of osteopathic medicine (COMs) are
      adequately preparing their graduates to meet the challenge of the geriatric
      demographic imperative, the authors surveyed the 16 COMs using a modified version
      of a survey conducted by Karuza and colleagues. Results were compared with those
      obtained from the Karuza and colleagues' survey of 73 allopathic medical schools.
      Overall, 88% of the COMs reported that they were committed to teaching geriatrics
      to undergraduate medical students, compared with 72% of the allopathic medical
      schools. Lack of time and appropriate clinical facilities were the two greatest
      barriers to committing more time to geriatrics in both osteopathic and allopathic
      undergraduate medical training programs.

PMID- 8979676
TI  - Diabetic retinopathy and blindness.

PMID- 8979677
TI  - Acute poisoning in children.
AB  - This prospective study comprised 120 children brought to the hospital with the
      history of acute poisoning. Poisonings occurred accidentally in 116 cases (96.7%)
      and 78 cases (65%) were children aged 1-4 years. Medical aid was sought earliest
      in case of children with animal bite and in infants. Kerosene and medications
      accounted for 72 cases (60%) of poisoning exposures. None of the care-takers of
      children received any instruction regarding prevention of accidents and poisoning
      prior to the episode, in spite of multiple contacts with health-care providers.
      Role of health education and other preventive measures are stressed.

PMID- 8979678
TI  - Reciprocal ST segment depression in acute myocardial infarction.
AB  - The significance of "reciprocal" ST segment depression and the utility of this
      finding in the electrocardiogram (ECG) of patients with myocardial infarction
      were studied in 100 cases of acute myocardial infarction. Out of these, 30 cases
      expired with 20 cases (66.6%) showing reciprocal ST depression in the ECG. In the
      remaining 70 cases, 24(34.3%) had reciprocal ST changes while 46(65.7%) had not.
      Twenty (83.3%) out of 24 cases had inferior wall infarction. The incidence of
      complications in the form of complete heart block and mortality was higher in the
      patients with reciprocal changes. The creatinine kinase levels were significantly
      elevated in patients with reciprocal changes than in the patients without.
      Predischarge treadmill test done in these cases having reciprocal changes showed
      positive stress tests. Coronary angiography was performed in the cases with
      reciprocal ST-T changes which revealed the presence of double-vessel disease or
      triple-vessel disease in most of these cases.

PMID- 8979679
TI  - Role of epidural medication in the treatment of resistant low back pain.
AB  - Two hundred and eight patients of low back pain were studied in the department of
      orthopaedic surgery, GSVM Medical College, Kanpur. The patients were put on
      intensive conservative treatment in the form of analgesics, hard bed rest, spinal
      extension exercises, traction and lumbosacral support. Thirty-two patients did
      not respond to this treatment and their symptoms were of more than 6 months
      duration and they were subjected to epidural injection of local anaesthetic
      agent, saline and corticosteroids. The failed 6 cases were investigated for
      consideration of surgery. The aim of this study is to develop standardised
      strategy for the treatment of low back pain. For the low back pain patients not
      responding to intensive conservative treatment, an idea has been put forward in
      the form of epidural medication prior to considering them to surgery to prevent
      unnecessary incidence of "failed back". A trial of epidural injection is
      suggested to avoid surgery.

PMID- 8979680
TI  - Renal cortical necrosis in pregnancy-related acute renal failure.
AB  - Of 63 patients of obstetrical acute renal failure, 15 cases (23.8%) had biopsy
      proven bilateral renal cortical necrosis. Remaining 48 patients (76.2%) had acute
      tubular necrosis. Eight of 39 cases in early pregnancy had cortical necrosis
      (postabortum) and 7 of 24 patients in late pregnancy revealed cortical necrosis.
      Diffuse and patchy cortical necroses were seen in 12 and 3 patients respectively.
      The incidence of cortical necrosis was almost equal in both early as well as late
      pregnancies. The high incidence (20.5%) of cortical necrosis following septic
      abortion remains the interesting feature of the present study in contrast to very
      low incidence (1.5%) of cortical necrosis in postabortum group in developed
      countries. The death occurred in most patients (14 ie, 93.3%) of cortical
      necrosis because of uraemic complications and sepsis.

PMID- 8979682
TI  - Medicine formulations for oral use for children.

PMID- 8979681
TI  - Study of burn sepsis with special reference to Pseudomonas aeruginosa.
AB  - Fifty cases of burn of different degrees were subjected to clinical and
      microbiological studies. A total of 60 isolates were obtained. Of these, 40
      (80.0% incidences) were Ps aeruginosa, 8 (16.0 incidences) Staph pyogenes, 6
      (12.0% incidences) Kl pneumoniae, 4 (80.0% incidences) Esch coli and 2 (4.0%
      incidences) C albicans. Monobacterial cultures showed isolations in 41 cases
      (82.0%) and 34 (68.0%) of them were Ps aeruginosa. At the time to admission 42
      cases (84.0%) were infected and during one week of hospitalisation another 8
      cases (16.0%) were infected yielding an overall infection rate of 100%. The
      commonest organism on admission and after hospitalisation was Ps aeruginosa with
      isolation rates of 60.0% (30) and 20.0% (10) respectively. Gram-negative bacilli,
      predominantly Ps aeruginosa were found in the lower part of the body with an
      incidence of 74.0% (37). Staph pyogenes was found in the upper half showing an
      incidence of 12.0% (6) next to 20.0% (10) incidence of Ps aeruginosa. The
      incidence of burn infection was high in patients with deep and major burn wounds,
      the bacterial isolates being 76.0% (38) and 80.0% (40) respectively. Silver
      sulphadiazine exhibited antimicrobial action in the range of 14 to 390 microM/ml,
      while cerium sulphadiazine had no inhibitory effect even up to 667 microM/ml on
      pseudomonas isolates. Zinc sulphadiazine was effective in inhibiting the growth
      of 10 isolates tested in 40 to 297 microM/ml range.

PMID- 8979683
TI  - Free radical induced diseases.

PMID- 8979684
TI  - Essential fructosuria--a case report.

PMID- 8979685
TI  - Bilateral cerebellar syndrome in a case of myxoedema.

PMID- 8979686
TI  - Annular pancreas in adults--diagnostic difficulties.

PMID- 8979687
TI  - Fine needle aspiration biopsy of astrocytoma brain--a case report.

PMID- 8979688
TI  - Family Planning Training Programme of the Indian Medical Association.

PMID- 8979689
TI  - A case of contrecoup vestibular injury.

PMID- 8979691
TI  - Mennonite roots of psychiatry in Kansas.

PMID- 8979690
TI  - Herniated disk: an obscure cause of neurogenic bladder in males.
AB  - A case of neurogenic bladder caused by asymptomatic protruding lumbar disc has
      been reported in the male. The diagnosis was established by Lapides
      supersensitivity cystometrogram study. After lumbar laminectomy, the bladder
      function returned to normal.

PMID- 8979692
TI  - Geriatric ethics: responsibilities and conspiracies.

PMID- 8979693
TI  - Adenocarcinoma of the anterior urethra in the male.

PMID- 8979694
TI  - Medullary sponge kidney.

PMID- 8979695
TI  - Self-help groups and health care reform.

PMID- 8979696
TI  - The first mass murder of modern times.

PMID- 8979697
TI  - Medico-legal implications of keyhole surgery.

PMID- 8979698
TI  - A layman's role on the GMC.

PMID- 8979699
TI  - Access to justice. Woolf on medical negligence.

PMID- 8979700
TI  - Quick connections. ISDN offers net-surfers speedy access at a cost.

PMID- 8979701
TI  - Michigan physician groups and the MSMS services they use.
AB  - According to Petoskey family practitioner and MSMS Membership Chair Louis R.
      Zako, MD, MSMS has adapted perhaps better than any other state medical society to
      the changing medical marketplace. "MSMS continues to provide traditional member
      services--such as excellent CME programs, cellular phone service and auto leasing
      -at extremely competitive prices. In recent years MSMS has also kept pace with
      the increasing complexity of the business side of medicine," Doctor Zako says.

PMID- 8979702
TI  - MSMS a full-service organization.
AB  - The practice of medicine faces unprecedented challenges today. Physicians in all
      practice types are faced with opportunities and choices not even thought of just
      two or three years ago.

PMID- 8979703
TI  - New group insurance trust product. MSMS members have another high-quality, low
      cost option.
AB  - A new health care plan customized to meet physicians needs is available to MSMS
      members through MSMS Group Insurance Trust.

PMID- 8979704
TI  - Creating a group practice? Strategic planning can prevent future problems.
AB  - As Michigan physicians have moved to forming group practices, MSMS has worked in
      a variety of ways to assist them. For instance, MSMS has contracted with some
      newly-forming groups to provide administrative services and even the
      administrators. James J. Aluia, senior consultant to Michigan Medical Advantage,
      and MSMS chief, physician networks and practice management, has served as
      administrator for newly-forming physician groups in the state and has learned a
      great deal about what it takes to organize a group. In this article, Michigan
      Medicine asks Jim what he's learned. His answers may benefit all physician
      groups.

PMID- 8979706
TI  - Speakers Bureau continues to get more requests.

PMID- 8979707
TI  - Michigan AIDS Fraud Task Force.

PMID- 8979705
TI  - Does your hospital fit your future? MSMS hospital financial information makes for
      good partnerships.
AB  - There is a growing interest among physicians in working with hospitals as
      partners in physician-hospital organizations, integrated delivery systems and
      other arrangements for managed care contracting. As we know from partnerships of
      all types, the more you know about your partner, the more efficient and effective
      the relationship.

PMID- 8979708
TI  - Pregnant women and HIV.

PMID- 8979710
TI  - Medicare: the next challenge.

PMID- 8979709
TI  - James P. Gallagher, MD. Scrappy former boxer fights to maintain physicians'
      voices.
AB  - It's been an adventurous life for James Gallagher, MD, from medical school in
      Ireland where he was a scrappy welterweight student boxer to one of the state's
      foremost cardiologists, and current president of the Wayne County Medical
      Society. Born in County Tyrone, Northern Ireland in 1932, the fifth in an
      ultimate full house of nine children, Doctor Gallagher attended medical school at
      the National University of Dublin.

PMID- 8979711
TI  - Nebraska physician manpower: an historical perspective.

PMID- 8979712
TI  - Effects of an orally effective endothelin-A receptor antagonist in dogs with
      pacing-induced heart failure.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor that has been shown to be
      elevated in the plasma of humans and animals with heart failure (HF). The role of
      an increase in endothelin in the setting of chronic HF is not known. METHODS: The
      present study was designed to determine the hemodynamic effects of a novel ET-A
      antagonist (PD-156,707) on the development of HF in dogs subjected to chronic
      ventricular tachycardia. Thirteen dogs were chronically instrumented to measure
      cardiac output (CO), left ventricular pressure (LVP), left atrial pressure (LAP),
      and arterial pressure (MAP). They were then paced at 210 bpm for 3 weeks and then
      at 245 bpm for 1 week (4th week). Two groups of dogs were studied, placebo group
      and a group of dogs administered the PD-156,707 compound (750 mg) orally three
      times per day beginning one day prior to the initiation of pacing. Hemodynamic
      measurements were made every three to four days during the four week pacing
      regimen. Arterial and venous blood samples were also taken to determine the
      plasma levels of endothelin-1 and PD-156-707. RESULTS: Endothelin-1 in plasma
      increased in all dogs with pacing induced HF (placebo control 1.57 +/- 0.5 vs
      placebo HF 2.2 +/- 0.6 pg/ml and drug control 1.5 +/- 0.16 v.s. drug HF 14.6 +/-
      3.8 pg/ml [p < 0.05]). Left ventricular end diastolic pressure (LVEDP) and LAP
      were equivalently and significantly elevated in both groups (p < 0.001) and LV
      dp/dt was significantly reduced (p < 0.001) in both groups 4 weeks after pacing.
      CO was slightly, but not significantly reduced after four weeks in both groups of
      dogs. However, administration of PD-157,707 significantly and profoundly reduced
      MAP at all times after 3 days of pacing (placebo HF[week 4]: 83.9 +/- 4.0 mmHg
      v.s. drug HF [week 4]: 72.4 +/- 2.3 mmHg [p < 0.05]) and total peripheral
      resistance (p < 0.05) at each time period following the induction of pacing.
      CONCLUSION: These data indicate that ETA blockade reduces afterload early during
      the development of chronic HF implicating endothelin-1 as an early compensatory
      hormone in HF. These results also suggest that blocking the ET-A receptor may
      have a role as an afterload reducer in the setting of human congestive heart
      failure.

PMID- 8979713
TI  - Ethical implications of type I, type II error in patient competency assessment.

PMID- 8979714
TI  - Sternomastoid rhabdomyoma mimicking a thyroid nodule.
AB  - A case is presented of a euthyroid male in whom a right thyroid mass was
      discovered. Physical displacement of the right thyroid lobe by a mass determined
      on CT scan. Scintigraphy and ultrasound showed the mass to be separate from the
      thyroid. Fine needle aspirations did not predict the tumor. Surgical removal of
      an adult rhabdomyoma was uneventful. This case and review of the literature
      demonstrate the rare presentation of a rhabdomyoma as a suspected thyroid nodule.

PMID- 8979715
TI  - Knee Arthrodesis.

PMID- 8979716
TI  - Measuring outcomes of care for substance use and mental disorders.

PMID- 8979717
TI  - Setting the context for measuring patient outcomes.

PMID- 8979718
TI  - Outcomes of psychiatric rehabilitation service delivery.
AB  - This chapter summarizes consumer outcomes following receipt of psychiatric
      rehabilitation services and reviews prior research studies in order to generate
      suggestions for improving the quality and consumer sensitivity of future outcomes
      research.

PMID- 8979719
TI  - Outcomes assessment: information for improving mental health care.
AB  - Findings from ongoing assessments in two states illustrate strategies for using
      outcomes information.

PMID- 8979721
TI  - Toward collaborative mental health outcomes systems.
AB  - A growing recognition that customers are important health partners has created
      the need for collaborative systems of accountability in behavioral health
      services.

PMID- 8979720
TI  - State of the science of mental health and substance abuse patient outcomes
      assessment.
AB  - This chapter explores mental health and substance abuse patient outcomes
      assessment and makes recommendations for advancing the field.

PMID- 8979722
TI  - Ethnic minority populations and mental health outcomes.
AB  - This chapter presents a framework for evaluating outcomes from mental health
      intervention in ethnic minority populations, reviews existing outcomes research,
      and describes ways to increase the quantity and quality of minority outcomes
      research.

PMID- 8979724
TI  - How will mental health outcomes data be used in private systems.

PMID- 8979723
TI  - What drives outcomes for emotional and behavioral disorders in children and
      adolescents?
AB  - The outcomes of child and adolescent disorders are multiply determined, and the
      range of factors influencing them requires full attention as the benefits of
      mental health services are assessed.

PMID- 8979725
TI  - Using outcomes measurement to improve quality and value.
AB  - The relationship between quality and value is demonstrated through improvement
      models and case examples. Principles and special issues relevant for improvement
      models in mental health are discussed.

PMID- 8979726
TI  - "Making the best of things": technology in American nursing, 1870-1940.

PMID- 8979727
TI  - The Johns Hopkins Training School of Nurses. A tale of vision, labor, and
      futility.

PMID- 8979728
TI  - Nursing in the American Army from the revolution to the Spanish-American War.

PMID- 8979729
TI  - I think you should get a job as a nurse.

PMID- 8979730
TI  - Miss Loane, Florence Nightingale, and district nursing in late Victorian Britain.

PMID- 8979731
TI  - Women's enterprise. Establishing the Lethbridge Nursing Mission, 1909-1919.

PMID- 8979732
TI  - Unheralded nurses. Male care givers in the nineteenth-century south.

PMID- 8979733
TI  - Sanitary reform and nursing. Edwin Chadwick and Florence Nightingale.

PMID- 8979734
TI  - Doctors and nurses in the London teaching hospitals. Class, gender, religion and
      professional expertise, 1850-1890.

PMID- 8979735
TI  - Sex education in American nursing. A historical view.

PMID- 8979737
TI  - Isolated tibial vessel disease: treatment options and outcome.
AB  - Tibial vessel disease is an important cause of limb ischaemia, particularly in
      diabetics. Revascularisation by angioplasty and bypass is increasingly feasible.
      The aim of this study was to review treatment and outcome in patients with this
      patterns of disease. We have performed 25 procedures in 20 patients since
      September, 1989. Six patients (5 diabetic) underwent 9 tibial angioplasties for
      stenotic lesions causing critical ischaemia or short-distance claudication. In 6
      procedures there was single vessel run-off. Eight angioplasties were
      radiologically successful with a median increase in ankle-brachial index (ABI) of
      0.15 [range: 0.00-0.44] at a median follow-up of 9 months. A further 4 patients
      (3 diabetic) with critical ischaemia underwent popliteal-distal, in-situ vein
      bypass for tibial occlusions. Distal anastomosis was onto the dorsalis pedis
      artery or distal anterior artery. Three grafts remain patent with successful limb
      salvage and ABI's greater than 1.0. Angioplasty is also useful for distal disease
      progression following femoro-popliteal bypass. Six patients with "at-risk" grafts
      underwent 8 tibial angioplasties for stenotic lesions in distal run-off.
      Radiologically, 6 procedures were successful with a median increase in ABI of
      0.21 [range: 0.00-0.38] at a median follow-up of 7 months. There were less
      favourable results when a "graft-distal" bypass performed to salvage an occluded
      femoro-popliteal graft with diseased run-off vessels. Three of 4 grafts
      reoccluded within 3 months, 2 patients requiring amputation. We advocate an
      aggressive policy towards localised distal disease causing foot ischaemia.

PMID- 8979736
TI  - Ventilation-perfusion mismatching as prognostic factor of respiratory failure
      after pulmonary resection.
AB  - This paper reports the results of a retrospective study undertaken to assess the
      reliability of regional ventilation-perfusion pulmonary scanning in predicting
      the remaining respiratory function (pFEV1), and the early and long-term outcome
      of 33 patients with chronic airways disease, submitted to pulmonary resection at
      the 1st Department of Surgery. All patients had been diagnosed as resectable with
      the traditional tools and had a traditional pFEV1 (tpFEV1) greater than 800 ml.
      All pFEV1 were re-calculated (npFEV1) with our new formula which also includes as
      lost for function all lung areas not to be resected with V/Q mismatching. Normal
      perfusion and ventilation distribution was found in 24.2% of patients in the
      lesion area and in 33.3% in the remaining pulmonary areas. An impairment of
      perfusion was observed in the lesion area in 72.7% of patients, in the remaining
      areas in 48.4%. An impairment of ventilation was observed in the same regions in
      66.6% and 48.5% of patients, respectively. Abnormality in ventilation/perfusion
      matching occurred in the lesion area in 15.2% of cases, in the ipsilateral lung
      areas in 18.2%, in the contralateral lung in 48.4% of cases. In predicting
      postoperative FEV1, and early and long-term mortality among our resectable
      patients, the tpFEV1 showed an accuracy of 91%, an index of resectability of
      93.7%, of unresectability of 0%. Our npFEV1 reached an accuracy of 94.4%, an
      index of resectability of 100% and an index of unresectability of 66.7%.

PMID- 8979738
TI  - Surgical management of ventricular septal rupture following myocardial
      infarction: the Hawaii experience.
AB  - OBJECTIVE: To assess the diagnostic and treatment methods of ventricular septal
      rupture following myocardial infarction in a small patient population.
      EXPERIMENTAL DESIGN: Retrospective medical record review. SETTING: Four Honolulu
      area teaching hospitals. PATIENTS OR PARTICIPANTS: Eighteen patients with
      ventricular septal rupture (VSR) following myocardial infarction (MI) between
      1979 and 1993. RESULTS: Ventricular septal rupture occurred more frequently in
      the elderly, in females and in those presenting for the first time with an MI.
      Thirteen patients (72%) underwent surgical repair including the two survivors.
      Three patients (17%) also underwent coronary artery bypass grafting, one of who
      survived. Very few of the patients had a history of stable angina pectoris before
      MI. Sudden deterioration in the patient's condition as manifested by tachycardia,
      hypotension and signs of right heart failure in those with an acute MI,
      especially if accompanied by a systolic murmur should encourage a search for a
      mechanical cause, especially a VSR. CONCLUSIONS: Two dimensional echocardiography
      or Swan-Ganz catheterization is 100% diagnostic and can be rapidly done at the
      bed side. Early surgical repair is important to the overall prognosis.

PMID- 8979739
TI  - Electrophysiological alterations in hepatic encephalopathy detected by brain
      mapping.
AB  - Analogical electroencephalogram has been used to study electric alterations in
      the brain during liver encephalopathy. We adopted digital technique brain mapping
      to study the electric background activity in the brain and to evaluate the
      diagnostic and prognosis usefulness of this technique compared with the methods
      routinely used in this disease. We studied 18 patients with liver cirrhosis and
      varying degrees of liver encephalopathy and 7 healthy control subjects to assess
      correlation between the severity of encephalopathy and abnormal electric activity
      in the brain, and to detect the main differences between the brain mapping
      findings obtained in the two groups. The findings revealed an overall reduction
      in the rhythm, increased amplitude and anomalous distribution of the waveforms in
      the cirrhotic patients. Although similar results have already been reported,
      brain mapping furnished prompt and more easily visualised findings. Moreover,
      brain mapping facilitated detailed analysis of wave amplitude, frequency and
      topographic location indicating that this technique is a valid tool in diagnosing
      brain disorders.

PMID- 8979740
TI  - Relationship of amiodarone to postoperative complications of transthoracic
      implantation of automatic implantable cardioverter defibrillators.
AB  - The purpose of this study is to report the results and complications associated
      with transthoracic placement of an implantable defibrillator and their
      relationship to amiodarone, and to identify clinical predictors of complications.
      There were 159 men and 41 women. The mean patients age was 61 +/- 11 years, and
      the mean ejection fraction was 0.33 +/- 0.14. Fifty one percent of patients
      developed complications including death in 14 patients (7%). Variables which
      differed in patients who died and those that did not were age, ejection fraction
      and New York heart failure classifications. Postoperative mortality was unrelated
      to amiodarone therapy. Twenty patients (10%) developed pneumonia and 15 patients
      (7.5%) developed respiratory failure. Clinical variables associated with the
      development of respiratory failure were age, amiodarone therapy and a prior
      history of pulmonary disease. Patients receiving amiodarone had a higher
      incidence of an elevated defibrillation threshold (> or = 25 joules) as compared
      with those not being treated with amiodarone. Clinical factors associated with an
      elevated defibrillation threshold were a history of a myocardial infarction,
      prior bypass surgery, and amiodarone. The results of this study demonstrate that
      placement of an implantable defibrillator using a transthoracic approach is
      associated with a high incidence of complications. Amiodarone therapy is
      associated with an increased incidence of pneumonia, respiratory failure, and
      elevated defibrillation thresholds.

PMID- 8979741
TI  - Renal function in endurance trained volunteers during prolonged restriction of
      muscular activity.
AB  - It has been demonstrated that changes in the functional status of the kidneys are
      basically responsible for the impaired fluid-electrolyte metabolism in physically
      healthy volunteers during hypokinesia (decreased number of walking steps/day).
      Thus, the objective of this investigation was to determine the functional changes
      of the kidneys of 20 endurance trained male volunteers aged 23 to 26 years with
      an average maximum oxygen uptake 65 ml.kg-1.min-1 during 364 days of hypokinesia
      (HK). All volunteers were on 14.6 km/day (10,000 running steps/day) prior to
      their exposure to HK. All volunteers were randomly assigned to one of the two
      groups: Ten volunteers were placed continuously under 14.6 km/day (10,000 running
      steps/day) (control subjects) and ten to 2.9 km/day (3,000 walking steps/day)
      (hypokinetic subjects). During the prehypokinetic period of 60 days and during
      the hypokinetic period of 364 days urinary and plasma electrolytes, glomerular
      filtration rate (GFR), renal plasma flow (RPF), were determined and isotope
      renographic tests were performed. The hypokinetic volunteers displayed a
      significant increase in urinary and plasma concentrations of electrolytes, a
      significant decrease in glomerular filtration rate and renal plasma flow,
      incorporation of isotope in the kidneys increased significantly while elimination
      of 131I-Hippuran from blood and kidneys decreased significantly. It is concluded
      that prolonged restriction of muscular activity induces significant changes in
      the examined renographic parameters of endurance trained volunteers which may be
      related to abnormalities of renal pelvis function or calyceal function.

PMID- 8979742
TI  - Breast cancer patients: long-term relapses.
AB  - The authors evaluated 200 cases of long-term relapses in patients subjected to
      mastectomy at least 8 years before and not given any hormonal or other therapy
      that would have significantly affected the course of the disease. A group of 200
      mastectomy patients with early relapses (within 3 years) was used as a control.
      The following parameters were compared: histologic type, singularity or
      multiplicity of the relapses at the time of the diagnosis, the patient's age at
      the time of the mastectomy, the presence of metastatic lymphnodes at the axilla,
      the clinical course of the disease after the diagnosis of relapse, and the
      presence of estrogen receptors in the primary tumor. There was a significant
      higher incidence of lobular histologic type in the group of patients with long
      term relapses (p < 0.001). The cases with long-term relapses showed a relatively
      lower number of relapses in local-region lymphnodes (p < 0.005) a higher number
      of cases with metastases to the axillary lymphnodes at the time of mastectomy (p
      < 0.001), a better clinical course (survival) after the diagnosis (mean 3 vs 2.6
      years), and more cases with estrogen receptors (p < 0.001) than controls.
      Premenopausal or postmenopausal status at the time of mastectomy was not
      significant. After a review of the literature, the authors conclude that relapses
      that appear after 8 years from the mastectomy occur almost exclusively in
      patients with a cancer for which the hormonal factor is very important. They
      hypothesize that even the 18 cases of the series who were without estrogen
      receptors in reality had receptors saturated by circulating estrogens or
      receptors for other hormones.

PMID- 8979743
TI  - Conservative management of cocaine-packet ingestion: experience in Milan, the
      main Italian smuggling center of South American cocaine.
AB  - OBJECTIVE: To assess retrospectively the effectiveness and the safety of the
      conservative medical management of asymptomatic cocaine body-packers. DESIGN:
      Case series collected during twelve years (1980-1992). SETTING: Milan Airports
      Health Center. Department of Surgery and Intensive Care Unit of San Raffaele
      Hospital-University of Milan. PARTICIPANTS: 189 suspected cocaine body packers
      (143 male, 53 female), aged between 18-53 years, were brought to our observation
      by customs after disembarking at the Milan International Airports of Malpensa and
      Linate. 61 subjects (32%) turned to be carriers of packets containing cocaine
      (ovules). INTERVENTIONS: Medical conservative treatment, based on close clinical
      observation and light solid diet, free assumption of liquids and oily laxatives.
      Plain abdominal X-ray and ultrasound were performed for the diagnosis of cocaine
      packet ingestion and then repeated up to the complete evacuation of all ovules.
      Two laparotomies with surgical removal of ovules in symptomatic patients (bowel
      obstruction and acute cocaine intoxication due to the intraluminal rupture).
      MEASURES: Physical examination with neurological assessment every 8 hours and
      vital signs (including blood pressure, heart frequency and temperature) every 4
      hours to detect complications (acute cocaine intoxication, bowel obstruction or
      perforation) secondary to cocaine packet ingestion. Structural features of the
      containers, cocaine amount per ovule, and rate and indications for surgical
      treatment have been reviewed. RESULTS: Evacuation period lasted from 3 to 6 days.
      Ingested containers varied from 52 to 117 with a mean of 88 +/- 13 ovules for
      each body packer. Total amount of recovered 95% pure cocaine hydrochloride was 41
      kilograms. Signs of cocaine toxicity and bowel obstruction requiring emergency
      laparotomy occurred in two cases (3.3%). Both patients recovered uneventfully.
      CONCLUSIONS: Conservative management during spontaneous evacuation of the
      containers is the first choice approach to the body-packet ingestion. Close
      clinical observation allows an early detection of the patients with complications
      requiring emergency surgical treatment.

PMID- 8979744
TI  - Adventitial cyst of the popliteal artery. Report of a case.
AB  - A case of cystic degeneration of the popliteal artery in a 58-year-old male is
      reported. Symptoms consisted of a claudication of abrupt onset and the correct
      diagnostic clue was initially given by magnetic resonance of the knee and
      confirmed by angiography. Treatment consisted of surgical removal of the cyst and
      saphenous vein angioplasty of the popliteal artery, with good anatomic and
      functional result at one year follow-up. Diagnostic tools and treatment of the
      condition are briefly discussed.

PMID- 8979745
TI  - Renal cell carcinoma in adolescents. A case report and review of the literature.
AB  - Renal cell carcinoma is rare in adolescents. Observation of a 16-year-old girl
      with a clear-cell carcinoma prompted us to review 372 published cases in
      adolescents. The tumor affects the sexes indifferently and has no side
      predominance. The incidence is higher in white races. The most frequent
      presenting sign is a palpable mass (52.7%). X-ray films typically show renal
      calcifications (25%). The most common histotype is the clear cell carcinoma
      (76.8%) and at diagnosis 59.5% of these tumors already extended beyond the
      kidney. The overall 5-year actuarial survival rate is 60.4%.

PMID- 8979746
TI  - Progress in health?

PMID- 8979747
TI  - Live viral vaccine potency: an index for assessing the cold chain system.
AB  - This study was carried out in the states of Lagos, Oyo, Osun, Nigeria and was
      designed to assess the efficiency of the cold chain and the potency of the
      vaccines from the National Cold Store through to the vaccination centres. Storage
      equipment was inspected and oral polio, measles and yellow fever vaccines were
      tested for potency. All 27 centres studied had adequately trained staff and
      storage was shown to be adequate at the National and State Cold Store Level.
      However, vaccines were adversely affected at the local Government Area Cold Store
      and Vaccination Centre Levels. Losses of potency of vaccines were shown: loss of
      titre of oral polio and yellow fever vaccine (0.03-0.9 log) was less than that of
      the measles vaccines (0.1-2.7 log). This was ascribed to thawing and refreezing
      due to equipment failure, to intermittent power supply in the absence of standby
      generators and mishandling of vaccines in the vaccine centres. This study
      revealed inadequacies at the Local Government Area and Vaccination Centre level.
      The cold chain should be examined in the remaining states of Nigeria and the
      inadequacies corrected.

PMID- 8979748
TI  - Descriptive epidemiology of injury in the south east: identifying priorities for
      action.
AB  - OBJECTIVE: To demonstrate the significance of injury in relation to other health
      problems, to describe the pattern of injury in one region of England, and to
      identify priorities for further epidemiological and prevention work. DESIGN:
      Cases were identified retrospectively from secondary data sources, namely using
      routinely collected data on deaths (OPCS anonymized death registrations for the
      period 1988-1991) and hospital in-patients (South Thames (East) RHA files of in
      patient episodes). Denominator data for rates were obtained from the 1991 mid
      year population estimates from the OPCS. SETTING: The cohort was defined as those
      resident in South Thames (East) during the study period, namely Kent, East
      Sussex, and South East London. The study period was 1988-1991 calendar years
      inclusive for the fatalities: and was the financial year from 1 April 1991-31
      March 1992 for injury resulting in hospital admission. MAIN RESULTS: Injuries
      were found to be the fifth leading cause of death, the third leading cause of
      potential years of life lost (PYLL), and the third most common cause of hospital
      bed utilisation. Injury rates varied dramatically with age, and sex. The highest
      injury death and hospitalization rates were amongst elderly people. The leading
      causes of injury death were motor vehicle traffic crashes (25%), and suicide
      (23%), and falls (15%); for injury hospitalizations they were falls (60% of bed
      days), and motor-vehicle traffic crashes (13% of bed-days). The most common
      places identified for the occurrence of injury death were road, home and
      residential institutions. Those injuries that accounted for most admissions to
      hospital were fractures (59% of bed-days). CONCLUSIONS: A number of areas have
      been identified as regional priorities. These are motor vehicle traffic crashes
      involving pedestrians (especially children under 15 and those aged 65 and over),
      car occupants and motor cyclists (especially young adult males); falls
      (especially those aged 65 and over); those occurring in residential institutions
      (especially for elderly people); fire and flames (affecting children under 15);
      suicide/self harm (all ages 15 and above); and homicide/assault (in males aged 15
      34).

PMID- 8979749
TI  - Ten years of experiences from a participatory community-based injury prevention
      program in Motala, Sweden.
AB  - Exploratory studies in the Scandinavian countries have suggested that the
      national cost of unintentional injuries is equal to 4% of the Gross National
      Product (GNP). One way for Swedish society to handle this situation has been
      through community-based injury prevention programs. This study used action
      research methods to supplement the understanding of the community development for
      injury prevention. The aim of this paper is to present the participative model
      used in one of the first of these programs, the Motala Injury Prevention Program,
      and lessons learned from the first 10 years of its operation. The program
      'succeeded' in 1993, when Motala Municipality formed a regular Safety Board
      chaired by the Municipal Commissioner. These are five main messages from the
      initial phases of the program: a community-based injury prevention program has to
      be regarded as a long-term project; preferably over more than a 10 year period,
      economic calculations are important in the community analysis phase of the
      program, inter-linkage between community organizations is essential in the design
      phase, the hand-over from the initial program developers to practitioners is
      critical in the implementation phase, it is important to maintain a high-quality
      data collection routine even after the conclusion of the community analysis phase
      of the program. These observations have a potential to be valid at least for
      Northern Europe, which, by comparison with other parts of the world is a
      relatively homogenous area with regard to external causes of injuries. Regarding
      other communities, there are known differences in injury rates and community
      organization.

PMID- 8979750
TI  - The prevention of skin cancer: is there a gap between evidence and practice?
AB  - BACKGROUND: Stabilizing of skin cancer incidence by 2005 is a Health of the
      Nation target and many purchasers and practitioners are actively endeavouring to
      meet it. This study aims to describe the extent and nature of primary and
      secondary prevention programmes amongst health authorities in the UK and general
      practices in Avon and to comment upon the evidential basis for these measures.
      METHODS: Questionnaire survey (with a second mailing to non-responders), sent to
      the 205 health authorities in the UK England, Wales, Scotland and Northern
      Ireland) and 179 general practices in Avon. RESULTS: Primary prevention
      programmes are being implemented by 89% of health authorities in the UK and 56%
      of general practices in Avon. Sun avoidance, and use of protective clothing and
      sunscreens were advised by over 90% of authorities with such programmes. 34% of
      general practices and 41% of health authorities were providing or purchasing
      secondary prevention programmes, ranging from conveying information about warning
      signs in skin lesions to undertaking full scale screening. CONCLUSION: Most
      authorities are appropriately promoting ultraviolet reduction by use of thickly
      woven clothing, hats and avoidance of the midday sun. There is greater
      uncertainty about the appropriate role of sunscreens, which have not been shown
      experimentally to reduce skin cancer incidence. Whilst there is some evidence of
      the effectiveness of campaigns to encourage rapid referral to pigmented lesion
      clinics, there is none to support screening for skin cancers by clinical
      examination and this approach should not be pursued under our current state of
      knowledge.

PMID- 8979751
TI  - Heart failure: the Cinderella of cardiology?
AB  - Heart failure is common and has a high mortality. These factors alone should make
      it an important public health issue. But the advent of new approaches to
      diagnosis and expensive forms of treatment have increased this importance to
      public health professionals. It has, however, received rather less attention than
      other manifestations of heart disease. This review summarises the major issues
      facing public health professionals seeking to develop strategies to tackle this
      condition. These include; what is known about diagnostic criteria, the prevalence
      of disease, including the important gaps in our knowledge about how it affects
      women, and the cost benefits, including the impact on quality of life, of
      emerging treatments. The review concludes with suggestions for research.

PMID- 8979752
TI  - Why don't all general practices offer structured diabetes care? A comparison of
      practices that do not with those that do.
AB  - The aim of the study was to examine whether the minority of practices not
      qualifying for payment for structured diabetes care programmes differ
      systematically from those that do. Information was collected for all
      Leicestershire general practices on practice size, population structure,
      deprivation indices, diabetes related admissions over two years and number of
      insulin treated patients on the district register. The 21 practices not offering
      structured diabetes care had a median list size of 3204, compared to 6340 for the
      other 124 practices (P < 0.001). Jarman and Townsend scores were higher for these
      practices and estimated prevalence of diabetes was 29% higher (95% CI: 26-32%).
      Crude admission rates were significantly higher in those practices not offering
      structured care. However rates adjusted for diabetes prevalence were similar
      (39.3 vs 39.2 per 100 insulin treated diabetics per year, P = 0.9). These results
      suggest that some practices face specific problems related both to small practice
      size and higher prevalence. If these issues are not addressed, inequalities in
      access to diabetes care between practice populations will persist. There is no
      evidence that the provision of structured care is associated with lower admission
      rates in this district. However more information, particularly in relation to
      prevalence of diabetes, is needed in order to accurately quantify this
      relationship. Variations in prevalence between practices should be adjusted for
      in any comparison of admission rates or spurious conclusions may be drawn.

PMID- 8979753
TI  - Prescribed medication and nutrition of social care patients in Crete, Greece.
AB  - OBJECTIVE: The aim of this study was to make a systematic registration of a group
      of 354 social care indigent patients in relation to: their pharmaceutical needs:
      the conditions for which it was prescribed, its cost, and details of
      prescriptions. In addition patients' eating patterns relating to and knowledge of
      how to use their medication was assessed. They were compared to a control group
      of 153 Social Security patients. SUBJECTS: The Social Care indigent patients were
      of low income, consisting of groups as unmarried mothers with their children and
      Greeks emigrants coming back home from other countries (Albania, Russia, Georgia,
      Ukraine, Romania etc.). The socio-demographic profiles of this group reveal an
      unemployment rate of 74% and an illiteracy rate of 18%. As regards marital
      status, 20% are bachelors and 12% divorcees. RESULTS: The results of the study
      indicated no significant difference between the two groups in the mean cost of
      prescription (40 ECU for Social Care patients vs 32 ECU for Social Security
      patients), in the mean number of medication per prescription (2.6 vs 2.6
      respectively), in the percentages of the Daily Defined Doses and the cost of the
      various categories of drugs. For both groups, the most common drugs were those of
      the Cardiovascular system (30% vs 26%), Gastrointestinal system (17% vs 27%) and
      Nervous system (16% vs 18%). The most common diagnosis was Hypertension (10% vs
      8%) and the most common drugs were Ranitidine (3% vs 2%), Diclofenac (3% vs 3%),
      Salbutamol (3% vs 3%) and Paracetamol (2% vs 2%). Significant differences between
      Social Care patients to Social Security patients respectively were found
      regarding: knowing how to take their medication correctly (47% vs 77%), knowing
      for how long treatment needed to be taken (21% vs 43%), requesting information
      from the pharmacist (39% vs 68%) knowledge of dietary instructions regarding
      medication (17% vs 41%) and in smoking more than 20 cigarettes per day (15% vs
      3%). CONCLUSIONS: The results indicated that the Social Care patients, in
      comparison with the patients of the Social Security, need more education and more
      help in the area of the proper use of drugs and in the personal contact that this
      procedure involves.

PMID- 8979754
TI  - Vision screening in junior schools.
AB  - A prospective study of routine school vision tests in 1809 children aged 8 and 10
      y was undertaken in schools in the Cambridge Health District over two years (1988
      1990) to establish whether a significant number of defects of vision were
      detected. Although the visual acuity of 31% of children who had an abnormal test
      was recorded as abnormal, most abnormalities were minimal. Only 15 (0.83%) had
      newly diagnosed problems requiring treatment. Almost all children with marked
      visual abnormalities had already been detected before school entry, at the 5 y
      school vision test or on another occasion. Near vision testing did not identify
      any previously undiagnosed child with significant defects who did not also have
      distant vision abnormalities. Satisfactory colour vision test results had been
      recorded for most children at the 5 y school entry vision test. These data do not
      justify the continued use of routine screening in junior schools.

PMID- 8979755
TI  - The centre for the vulnerable child: a new model for the therapeutic provision
      for abused children and their families.
AB  - In the last decade in Scotland there has been a rise in the number of known cases
      of children and adolescents who have experienced sexual abuse and a rise in the
      number of cases entering treatment after detection. This is putting a
      considerable strain on existing child and adult mental health services. As part
      of the response to this problem a new service was set up in Fife, the Centre for
      the Vulnerable Child, to provide an integrated focus for therapy, in-service
      training, consultancy and research into the area of sexual abuse. The Centre has
      strong links with the local joint police and social work Child Protection Unit
      with which it shares premises. Early indications are that the service is dealing
      primarily with more severely abused children. An evaluation is underway to assess
      both user satisfaction and the impact of this new service on measurable health
      and social outcomes among sexually abused children and their families.
      Professionals who have referred patients and clients to the Centre are largely
      satisfied with its work and an instrument for seeking the views of referred
      children is under development.

PMID- 8979756
TI  - Partner's smoking: a major determinant for changes in women's smoking behaviour
      during and after pregnancy.
AB  - To study determinants for changes in maternal smoking behaviour during and after
      pregnancy, questionnaire information on smoking habits was recorded in a cohort
      of 3710 Norwegian women during early pregnancy, at delivery, and one year later.
      Of 3039 cohabiting women with complete information on smoking at all three
      occasions 31% smoked in early pregnancy 23% in the late pregnancy and 28% one
      year after delivery. Among the cohabiting mothers who smoked in early pregnancy,
      44% stopped during pregnancy. After adjusting for confounding factors, the odds
      ratio for smoking cessation among these women who had cohabitants who smoked as
      opposed to not smoking was 0.2 (95% CI: 0.1-0.2). Among cohabiting non-smoking
      women during late pregnancy the odds ratio for being a smoker one year after
      child birth was 3.0 (95% CI: 2.2-4.0), if their cohabitants smoked as opposed to
      not smoking. The women's smoking behaviour changes considerably during and after
      pregnancy and their cohabitants' smoking seems to be a major determinant for
      changes in their smoking behaviour.

PMID- 8979757
TI  - Addressing implementation problems of Texas Medicaid reform.

PMID- 8979759
TI  - Loosening up antitrust.

PMID- 8979758
TI  - It takes teamwork.

PMID- 8979760
TI  - Welfare reform.

PMID- 8979761
TI  - TB roars back.

PMID- 8979762
TI  - Screening for breast and prostate cancer: a survey of Texas primary care
      physicians.
AB  - Screening for breast and prostate cancer is underutilized, and according to
      previous studies, physicians often fail to comply with recommended screening
      guidelines. We surveyed Texas physicians to determine their screening behaviors
      and their compliance with National recommendations. For women aged 40 through 49
      years, 75.5% of respondents recommend mammography every 1 to 2 years, and 8.4%
      suggest it annually. For women 50 years and older, 16.1% of clinicians screen
      every 1 to 2 years, and 81.4% recommend annual mammography. Thus, 71.7% of
      physicians match or exceed the American Cancer Society guidelines for screening
      mammography in women 40 years and older. Texas physicians also report a high rate
      of prostate cancer screening, with more than 90% of respondents offering testing
      by age 60 years. The screening method preferred by 72.0% of clinicians combines
      digital rectal examination and the prostate-specific antigen blood test. Overall,
      the screening practices reported by this sample of Texas physicians compare very
      favorably with those reported by other groups.

PMID- 8979763
TI  - Does the hepatitis G virus cause hepatitis?
AB  - As many as 10% to 20% of presumed viral hepatitis cases are serologically non-A
      E. Recently, two groups of investigators independently isolated a viral agent
      that may contribute to non-A-E viral hepatitis. This virus, named hepatitis G or
      GB virus C (HGV/GBV-C), is present in about 2% of accepted US blood donations.
      This paper reviews both the details involving isolation of the virus and the
      current epidemiological data, and shows that the accumulated evidence to date
      does not support the claim that HGV/GBV-C is responsible for non-A-E viral
      hepatitis.

PMID- 8979764
TI  - Effect of sperm dose on pregnancy rate from intrauterine insemination: a
      retrospective analysis.
AB  - Both the number of motile spermatozoa inseminated and the site of insemination
      have been correlated with the probability of pregnancy in patients inseminated
      with donor sperm cells from fertile men. Nevertheless, more data on the minimum
      sperm dose required to achieve a pregnancy are needed to understand this apparent
      relationship. We analyzed retrospectively 2280 cycles of intrauterine
      insemination to test the hypothesis that intrauterine insemination requires a
      minimum number of motile sperm cells to maximize the pregnancy rate. Our analysis
      of 1761 cycles of intrauterine insemination using from 200,000 to more than 200
      million motile sperm cells showed no significant relationship between sperm dose
      and pregnancy rate.

PMID- 8979765
TI  - Rationale for a medical society sponsored expert witness program.
AB  - The medical profession has many avenues by which to improve the present tort
      system as it regards medical negligence cases. One such avenue is a medical
      society sponsored expert witness program through which medical societies can
      assure that each case is being evaluated properly by an ethical and responsible
      physician. This effort will assist attorneys in weeding out medical negligence
      cases that are without merit and shepherding meritorious cases towards
      appropriate settlement. Such a program would be a positive step in discouraging
      the legal profession's use of the "professional expert." Finally, such a program
      might also provide funds for other worthwhile medical/legal projects.

PMID- 8979766
TI  - New treatments for movement disorders?

PMID- 8979767
TI  - Cysteinyl leukotriene receptors in the human lung: what's new?

PMID- 8979768
TI  - 7TM receptors: 'locks' and 'keys'?

PMID- 8979769
TI  - NMDA receptors: from genes to channels.
AB  - N-methyl-D-aspartate receptors belong to the family of ionotropic glutamate
      receptors. NMDA receptors were named after the specific glutamate-like synthetic
      agonist N-methyl-D-aspartate. In the past decade, an increasing number of
      functional sites have been discovered and used to refine the operational
      definition of NMDA receptors. The goal to characterize the molecular substrate
      underlying the heretofore strictly operationally defined NMDA receptors has come
      into reach following the cloning of a number of cDNAs coding for NMDA receptor
      subunits. However, in their review, Nikolaus Sucher and colleagues show that
      caution should be exercised in comparing the pharmacological properties of
      recombinant NMDA receptors to those of native neurones. Future work on NMDA
      receptors will be challenged to reconcile disparate effects obtained with
      recombinant versus native receptors.

PMID- 8979770
TI  - Involvement of biogenic amines and amino acids in the central regulation of
      cardiovascular homeostasis.
AB  - Biogenic amines and amino acids have been implicated in central cardiovascular
      homeostasis. Initially, drugs were injected into the brain and their effects on
      blood pressure were investigated. Other approaches allowed endogenous
      neurotransmitters released in the extracellular space of brain structures
      involved in cardiovascular regulation to be identified. As Nicolas Singewald and
      Athineos Philippu outline, even slight disturbances in blood pressure and/or
      isovolaemia lead to marked changes in the release rates of biogenic amines and
      amino acids in various brain structures. Blood pressure homeostasis is maintained
      with the participation of several brain regions and neurotransmitters which
      possess the same or opposing functions when released from CNS neurones.

PMID- 8979771
TI  - Pharmacology of adenosine A2A receptors.
AB  - Adenosine A2A receptors, which have been cloned from several mammalian species,
      are activated by physiological concentrations of adenosine to stimulate the
      formation of cAMP and other mediators. The A2A receptors are found on neutrophil
      leukocytes, platelets, blood vessels and, very abundantly, on some cells in the
      CNS. In the caudate nucleus they coexist with dopamine D2 receptors, and
      stimulation of A2A receptors causes a decrease in D2 receptor-mediated
      neurotransmission. Thus, drugs that act on A2A receptors can be used to modify
      dopaminergic neurotransmission known to be important in neurological and
      psychiatric disorders. In this review, Ennio Ongini and Bertil Fredholm describe
      how recently developed potent and selective A2A receptor antagonists can be used
      to delineate the physiological and pathological processes regulated by A2A
      receptors. Results from in vitro and in vivo pharmacology studies strengthen the
      notion that A2A receptors are an interesting target for drug development.

PMID- 8979772
TI  - Function and regulation of the beta 3-adrenoceptor.
AB  - The cloning, sequencing and expression in model systems of the previously
      unidentified beta 3-adrenoceptor recently led to an extensive functional
      characterization. Ligand binding and adenylate cyclase activation studies helped
      define a specific profile that is quite distinct from that of the beta 1- and
      beta 2-adrenoceptors, but strongly reminiscent of most of the 'atypical' beta
      adrenoceptor-mediated responses reported in earlier pharmacological studies. More
      recently, a naturally occurring variation in the human beta 3-adrenoceptor has
      been correlated with hereditary obesity and with increased dynamic capacity to
      add on weight and develop non-insulin dependent diabetes in Western obese
      patients. Donny Strosberg and France Pietri-Rouxel describe how results now
      provide a consistent picture of an important role for the human beta 3
      adrenoceptor in the regulation of lipid metabolism and as an obvious target for
      drugs to treat some forms of obesity and diabetes.

PMID- 8979773
TI  - The current global situation of the HIV/AIDS pandemic.

PMID- 8979774
TI  - Medical education for the millenium.

PMID- 8979775
TI  - Cancer in Northern Ireland by 2002.
AB  - An estimate of cancer deaths and incidence for the years 1997 and 2002, taking
      account of current trends and population projections for Northern Ireland is
      presented below. These numbers will be of value to those planning services and,
      in particular, for those implementing the report "Cancer Services - Investing for
      the Future". Cancer deaths are expected to rise by almost 13% to 4056 by the year
      2002. Marked rises are expected in the number of deaths from cancer of the lung,
      oesophagus, kidney, bladder and prostate with smaller rises in deaths from breast
      and pancreatic cancer. The fall in stomach cancer is expected to continue as is
      the trend of lower deaths from cervical cancer. Deaths from cancer of the colon
      and rectum are expected to remain static. Estimates of cancer incidence currently
      and for the years 1997 and 2002 are also included. The impact of tobacco use by
      the population, which poses a current and future serious threat to public health
      is highlighted.

PMID- 8979776
TI  - Hereditary breast cancer in Northern Ireland.
AB  - The aim of this investigation was to document hereditary breast cancer in
      Northern Ireland. Family history details from over nine hundred women were
      obtained by postal survey and one hundred and twenty nine home visits were
      carried out to collect pedigree information. The families documented varied in
      the number of affected women from three, which was the minimum criteria for
      inclusion, to a maximum of nine and many families described other features of
      hereditary disease such as bilateral breast cancer, ovarian and gastrointestinal
      malignancies.

PMID- 8979777
TI  - Babies born under 1000 g--perinatal outcome.
AB  - Improved survival of very pre-term infants is a result of advances in obstetric
      and neonatal medicine. To provide relevant data for a Northern Ireland population
      group, we evaluated mortality and morbidity of extremely low birthweight (ELBW; <
      1000 g) infants from a tertiary referral neonatal unit. Seventy-seven ELBW
      infants were admitted on the first day of life during the period April 1990 to
      April 1992. Mean (SD) gestational age (GA) was 26.2 (2.1) weeks and birthweight
      (BW) was 781 (132) g. The degree of severity of initial illness was high, with a
      mean (SD) CRIB (clinical risk index for babies) score of 7.4 (4.2). Fifty (65%)
      babies survived, being discharged home at a mean (SD) age of 95 (34) days.
      Survivors were more likely to have received maternal steroid therapy or been born
      in this hospital. Ten (20%) of the survivors had evidence of severe neonatal
      brain injury or cranial ultrasonography--Papile grade 3 or 4 intraventricular
      haemorrhage (IVH) or periventricular leucomalacia (PVL). Survival rate of ELBW
      infants without severe brain injury was 54% overall; this ranged from 0% in ELBW
      infants born at 23 weeks GA and 33% at 24 weeks GA to 85% at 27 weeks GA.

PMID- 8979778
TI  - Experience with schistosomiasis in Northern Ireland.
AB  - Five cases of schistosomiasis have been recorded in the Belfast City Hospital
      Histopathology Laboratory over the last three years. The sites of infection have
      included the colon, bladder, uterus and seminal vesicles. All the infected
      individuals had visited Africa. Three of them were health care workers. The
      clinician must maintain a high index of suspicion when treating those with a
      history of travel and risk of exposure to this infection. Diagnosis is made even
      more critical as the condition is treatable, and serological markers can identify
      those with occult infection.

PMID- 8979779
TI  - Casualties of the sun.
AB  - A retrospective review was carried out of all sunburn related attendances, during
      the periods 1/6/94-31/8/94 and 1/6/95-31/8/95, at the four A&E departments and at
      one of the general practices within the Northern Health and Social Services Board
      area. Four hundred and thirty patients had attended. The modal age group was 16
      30 years. More males presented than females. Within the sexes more males
      presented in the under 16 years and over 30 years age group, while females were
      more common in the 16-30 years age group. There was documentation of blisters in
      30% of patients. Those with blisters were more likely to be under 16 years and
      male. In females the most and least commonly affected areas correlated with the
      most and least commonly affected areas for cutaneous malignant melanoma. In these
      days of limited resources it is important to use epidemiological data such as
      this in order to contribute to the development of health promotion programmes and
      campaigns.

PMID- 8979780
TI  - Randomised controlled trial of ranitidine versus omeprazole in combination with
      antibiotics for eradication of Helicobacter pylori.
AB  - This study compared high dose ranitidine versus low dose omeprazole with
      antibiotics for the eradication of H pylori. 80 patients (mean age 48 years,
      range 18-75) who had H pylori infection were randomised in an investigator-blind
      manner to either a two-week regime of omeprazole 20 mg daily, amoxycillin 500 mg
      tid and metronidazole 400 mg tid (OAM), or ranitidine 600 mg bd, amoxycillin 500
      mg tid and metronidazole 400 mg tid (RAM), or omeprazole 20 mg daily and
      clarithromycin 500 mg tid (OC), or omeprazole 20 mg daily and placebo (OP). H
      pylori was eradicated in 6 of 19 patients in the OAM group (32%); 8 of 18 in the
      RAM group (44%), 4 of 15 in the OC group (27%); none of 18 in the OP group (0%).
      [< P0.005 for OAM, RAM, OC vs OP; P = N.S. between OAM, RAM, OC]. Overall
      metronidazole resistance was unexpectedly high at 58%. Eradication rates in
      metronidazole sensitive patients were 71% (5/7) and 100% (3/3) for OAM and RAM
      respectively. In conclusion, H pylori eradication rates using high dose
      ranitidine plus amoxycillin and metronidazole may be similar to that of low dose
      omeprazole in combination with the same antibiotics for omeprazole with
      clarithromycin. Overall eradication rates were low due to a high incidence of
      metronidazole resistance but were higher in metronidazole-sensitive patients.
      Even high dose ranitidine with two antibiotics achieves a relatively low
      eradication rate. These metronidazole-based regimens cannot be recommended in
      areas with a high incidence of metronidazole resistance.

PMID- 8979781
TI  - A comparison of intra-arterial digital subtraction angiography with Doppler
      sonography in the assessment of carotid arterial stenosis.
AB  - A comparison is made of the use of selective intra-arterial subtraction
      angiography and doppler sonography in the assessment of disease in 206 carotid
      arteries. Maximal stenoses in each of the internal, external and common carotid
      arteries were recorded and compared using both modalities. In 93% of cases,
      arteries reported as normal ultrasonically were also found to be normal on
      angiography. However, agreement between the modalities in the assessment of
      severe stenoses was rather less at 79%. Overall agreement between the two
      modalities was good using statistical analysis (weighted Kappa). It is our view
      that ultrasound is reliable in normal vessels, but where significant disease is
      present the rate of error between the two modalities is too high to warrant
      omission of angiography.

PMID- 8979782
TI  - Re-admission of elderly patients after in-patient rehabilitation.
AB  - The re-admission rates of a cohort of 97 elderly patients discharged from
      hospital were ascertained. The overall re-admission rate at 30 days was 15%, at
      90 days 24% and at 180 days, 30%. On 4 occasions (9%) re-admission was deemed
      avoidable by the general practitioner. Deterioration of existing disease
      accounted for 16 (36%) and a new medical event for 22 (49%) re-admissions.

PMID- 8979783
TI  - Clinical trial comparing artificial rupture of membranes plus oral PGE2 tablets
      versus artificial rupture of membranes plus intravenous oxytocin for induction of
      labour in primigravid patients at term.
AB  - We report the results of a pilot study conducted to compare the efficacy of oral
      prostaglandin E2 versus intravenous oxytocin in inducing labour after lower
      amniotomy in 20 primigravid patients at term. The results suggest no significant
      differences in the performance of each group for the induction to delivery
      interval, the mode of delivery, the Apgar score at five minutes or for third
      stage abnormalities. However, the use of oral PGE2 allows the patient
      unrestricted mobility and avoids the discomfort of i.v. infusions.

PMID- 8979784
TI  - Laparoscopic-assisted vaginal hysterectomy: initial experience.
AB  - We reviewed the charts of 36 women who had laparoscopic-assisted vaginal
      hysterectomies (LAVH) at Belfast City Hospital over a 3 year period. The average
      operating time was 105 minutes. However, patients had a shorter duration of
      hospitalization (< 4 days for 96% of patients) with rapid recuperation (3.4
      weeks). Complications occurred in 7 patients. One patient developed a vesico
      vaginal fistula which was diagnosed post operatively and successfully repaired 5
      months later. Technical difficulty was reported in one patient because of
      significant adhesions and poor access due to obesity. She went on to develop a
      pelvic abscess which was drained. Patient satisfaction with the operation was
      high. LAVH is an effective operation in selected cases and in experienced hands
      the complication rate is low. In the future it may become a valid alternative to
      open abdominal hysterectomy.

PMID- 8979785
TI  - Thomas Ferrar, MB, LRCSI (1797-1837): the absentee professor of surgery at the
      Royal Belfast Academical Institution.
AB  - Thomas Ferrar was the second professor of surgery in the short-lived (1835-1849)
      medical school of the Royal Belfast Academical Institution. Appointed on 5 July
      1836 he failed to turn up for the winter session and was accordingly discharged
      on 29 November. He died in Sligo in the following June aged 39. Nothing has been
      written about Ferrar who survives as a mere foot-note in Belfast medical history.
      The events leading to his dismissal are, however, unusual, equivocal, and worth
      recounting. The facts suggest that the Institution was clearly justified in its
      action but that Ferrar emerges with some credit for a certain if misplaced high
      mindedness though overshadowed by his patent derelictions.

PMID- 8979786
TI  - A left sided neck mass.

PMID- 8979787
TI  - Phentolamine mesylate can alleviate the nausea and vomiting associated with liver
      metastasis.

PMID- 8979788
TI  - Cyst of pregnancy.

PMID- 8979790
TI  - Clonal architecture of the mouse retina.
AB  - The study of chimeric retinas has yielded insight on the early development of
      retina. The close match in chimerism ratios between right and left retinas is
      significant and supports the idea that both retinas originate from a common
      population of progenitors. We are able to estimate numbers of progenitor cells
      that contribute to the formation of the retina and the approximate time at which
      this small group is isolated from surrounding prosencephalic cell fields. These
      cells undergo at least five rounds of division before the first retinal neurons
      are generated. The mouse retina is not build from the center outward. There is
      simultaneous expansion and differentiation in all parts of the retina and as a
      result clones are not arranged in wedges. Instead the mouse retina is a patchwork
      of clones that do not differ greatly in size from center to periphery. The most
      consistent radial feature in mouse retina is a raphe left at the line of fusion
      of the margins of the ventral fissure. Processes that shape the clonal patchwork
      are both passive and active, intrinsic and extrinsic. Certain features of the
      clonal architecture of the retina, such as the size differences of clones are
      primarily passive responses to extrinsic forces on progenitor cells and their
      progeny. The fifteen-fold range in the size of cohorts is not due to intrinsic
      differences in the proliferative capacity of individual progenitor cells, but is
      due to the extent of cell movement and mixing at early stages of development. In
      contrast, active or intrinsic processes are illustrated by the partial (and still
      controversial) restriction of retinal progenitors, the possible clonal
      differences between ganglion cells with crossed and uncrossed projections, and
      the consistent differences in ratios of albino and pigmented genotypes in
      peripheral and central retina.

PMID- 8979789
TI  - Malignant lymphoma of the scrotum and Wegener's granulomatosis of the penis-
      genital presentation of systemic disease.

PMID- 8979791
TI  - Early development of the cerebral cortex.

PMID- 8979792
TI  - Growth cone behaviors during axon guidance in the developing cerebral cortex.

PMID- 8979793
TI  - Specification of layer-specific connections in the developing cortex.
AB  - One of the basic tasks of neurobiology is to understand how the precision and
      specificity of neuronal connections is achieved during development. In this paper
      we reviewed some recent in vitro studies on the developing mammalian cerebral
      cortex that have been made towards this end. The results of these experiments
      provided evidence that membrane-associated molecules are instrumental for the
      formation of specific afferent and efferent cortical projections. Substrate-bound
      molecules guide growing axons towards their target, regulate the timing of
      thalamocortical innervation and mediate target cell recognition. Moreover, a
      newly described glycoprotein, defined by a monoclonal antibody, revealed a
      molecular heterogeneity in the developing white matter. Since this molecule has
      opposite effects on thalamic and cortical axons, it might play a role in the
      segregation of axons running to and from the cortex. Substrate-bound cues are
      important during the formation of local cortical circuits. In vitro assays
      demonstrated that molecular components confined to individual cortical layers
      control the laminar specificity of cortical axon branching. This suggests that
      similar developmental strategies contribute to the laminar specification of
      extrinsic and intrinsic cortical circuits. Thus substrate-bound molecules might
      provide the framework for subsequent activity-dependent mechanisms that control
      the elaboration of precise connections between the cortical columns. A major
      challenge ahead is to identify the factors that mediate these processes and to
      determine their mode of action. Recently, two families of proteins, the netrins
      and the semaphorins/collapsins, have been identified as growth cone signals in
      the developing spinal cord (reviewed in Goodman, 1994; Colamarino and Tessier
      Lavigne, 1995a; Dodd and Schuchardt, 1995; Kennedy and Tessier-Lavigne, 1995).
      Semaphorins/collapsins appear to regulate axonal guidance by repelling growth
      cones and by inhibiting axonal branching and synapse formation. Originally,
      netrins have been purified as diffusible chemoattractants for commissural axons
      of the dorsal spinal cord, but it is now well established that they can also
      function as chemorepellent factors for other classes of neurons. Since netrins
      are related to extracellular matrix components and since they can bind to the
      cell surface, they might also act as local guidance cues. A possible role of
      netrins and semaphorins/collapsins in the development of cortical connections is
      likely to be resolved in the near future. The identification of the factors that
      regulate specific branching patterns of cortical neurons might provide a better
      understanding of cortical development, but it might also be relevant to some
      aspects of plasticity and repair in the adult cortex.

PMID- 8979794
TI  - Cellular mechanisms regulating neurite initiation.

PMID- 8979796
TI  - Retinal axon divergence in the optic chiasm: growth cone behaviors and signalling
      cells.

PMID- 8979795
TI  - Prenatal development of axon outgrowth and connectivity.

PMID- 8979797
TI  - Cell adhesion/recognition molecule-mediated steps during the guidance of
      commissural and motor axons.

PMID- 8979799
TI  - Unilateral containment of retinal axons by tectal glia: a possible role for
      sulfated proteoglycans.
AB  - (1) A distinct group of radial glia resides along the roofplate of the
      mesencephalon. Results of experiments, in which the neonatal tectum is
      manipulated surgically, point to the involvement of these glia in
      compartmentalizing retinotectal axons to one side of the midbrain. (2)
      Immunohistochemical studies document that the GAGs CS and KS are expressed along
      these midline glia during development: their expression occurs after the
      intertectal axons grow across the midline, but is coincident with the time of
      ingrowth of retinotectal axons, which fail to cross the midline. Together with
      results of in vitro experiments from other laboratories, these observations
      suggest that CS and KS are involved in the barrier function of the midline cells.
      (3) Preliminary data on biochemical characterization of PGs in developing tectum
      indicate that similar PG core proteins are found in the midline region as well as
      in the lateral tectum, whereas metabolic labeling shows a significantly higher
      uptake of radioactive sulfates along the midline. Thus differential glycosylation
      of proteins along the midline is likely, along with the possibility that it is
      the sugar chains which contribute to the barrier function of the raphe glia.
      Taken in the context of what we currently know about the biochemical
      heterogeneity of PGs, their developmental expression, and their functions in
      relation to the growth of axons from a variety of different neuronal cell types,
      it is clear that the analyses of interactions between PGs and growing axons must
      occur at several different levels, not the least of which involves a detailed
      understanding of the milieu in vivo within which these interactions take place.

PMID- 8979798
TI  - Extracellular matrix in early cortical development.
AB  - Studies of the distribution and production of ECM components during development
      of the cerebral cortex have suggested several hypotheses regarding their
      functional role. In the earliest stages of cortical development, fibronectin is
      produced by cells in the ventricular zone throughout the telencephalic vesicle,
      where it may serve as a part of the local environment that supports cell division
      and determines cell fate. Fibronectin is also distributed along radial glial
      processes. It is closely associated with preplate neurons, as are chondroitin
      sulfate proteoglycans and several other ECM components. This association
      continues as preplate cells are divided into the marginal zone and subplate by
      the invasion of cortical plate neurons, suggesting that ECM, preplate cells and
      radial glia serve as a scaffold for cortical plate formation. Fibronectin is also
      produced by migrating neurons, but only by those moving into specific cortical
      domains, suggesting that it may help neurons destined for specific targets
      discriminate between adjacent glial guides. A recently defined ECM-like protein,
      reelin, is absent or abnormal in the reeler mutant mouse in which cortical
      neurons are severely malpositioned. Reelin is produced by marginal zone cells and
      is therefore appropriately located to serve as a stop signal for migrating
      neurons. Axons leaving the cortical plate cross the CSPG-rich subplate, then turn
      to follow a path containing much less CSPG. In contrast, the cortical trajectory
      of thalamic axons is centered on the subplate, indicating that CSPGs in the
      subplate are not a barrier to axon outgrowth and may instead be serving as
      guidance cues that distinguish afferent from efferent pathways. Neurocan, a CNS
      specific CSPG with many molecular features that indicate roles in cell-cell and
      cell-substrate interactions, is the only CSPG defined to date whose distribution
      supports a role in distinguishing afferent from efferent pathways.

PMID- 8979800
TI  - Proteoglycans and other repulsive molecules in glial boundaries during
      development and regeneration of the nervous system.

PMID- 8979801
TI  - Axon decussation and midline glia in the developing ferret auditory hindbrain.

PMID- 8979802
TI  - Myelin-associated neurite growth inhibitors: regulators of plastic changes of
      neural connections in the central nervous system.

PMID- 8979803
TI  - NMDA-receptor-dependent synaptic plasticity in the visual cortex.

PMID- 8979804
TI  - The role of excitatory amino acid transmission in development and plasticity of
      SI barrel cortex.

PMID- 8979805
TI  - The role of NMDA receptors and nitric oxide in retinogeniculate development.

PMID- 8979806
TI  - Developmental mechanisms for regulating signal amplification at excitatory
      synapses in the neocortex.

PMID- 8979807
TI  - Glutamate receptors and development of the visual cortex: effect of metabotropic
      agonists on cAMP.
AB  - Glutamate receptors are more active in several respects in young animals than in
      adults. Here we examine the effect of metabotropic glutamate agonists on rat
      cortical cAMP during and after the critical period for visual cortex plasticity.
      Quisqualate produced a substantial increase in cAMP, which was larger during the
      critical period than in the adult. The increase was not affected by CNQX or APV,
      showing that it was not due to the action of quisqualate on ionotropic glutamate
      receptors. Both Type I mGluRs (mGluRs 1 and/or 5) and Type II mGluRs (mGluRs 2
      and/or 3) probably contributed to the cAMP increase because (i) ACPD and L-CCG-I,
      which are more active on Type II mGluRs, were more effective than DHPG, which is
      more active on Type I mGluRs; and (ii) there was a significant difference in the
      effect of ACPD on the increase in cAMP, comparing mGluR1 knockout mice with
      control mice. Agonists which produce large stimulation of cAMP production (ACPD,
      L-CCG-I), as well as L-AP4, also produced small attenuations of forskolin
      stimulated cAMP, but only at high concentrations. Thus, we conclude that it is
      the stimulation and/or potentiation of cAMP production that is significant,
      rather than the attenuation of forskolin-stimulated cAMP. Since this stimulation
      and/or potentiation is higher during the critical period than in the adult, and
      the cAMP second messenger system has been implicated in hippocampal plasticity,
      it may also play a role in visual cortex plasticity.

PMID- 8979808
TI  - Nitric oxide and the developmental remodeling of retinal connections in the
      brain.

PMID- 8979809
TI  - Cellular mechanisms underlying the formation of orderly connections in developing
      sensory pathways.

PMID- 8979810
TI  - Control of retinotectal axon arbor growth by postsynaptic CaMKII.

PMID- 8979811
TI  - Pre- and postnatal expression of amino acid neurotransmitters, calcium binding
      proteins, and nitric oxide synthase in the developing superior colliculus.
AB  - Neurons within the superior colliculus (SC) contain a variety of neurochemicals,
      including the amino acid neurotransmitters GABA and glutamate, the calcium
      binding proteins calbindin and parvalbumin, and the neuromodulator nitric oxide.
      We have examined the development of expression of these substances using antibody
      immunocytochemistry. These results are summarized in Fig. 10. GABA and calbindin
      are expressed very early in development, at a time when cells are still dividing
      and migrating from the subventricular zone. The expression of both GABA and CB is
      maximal at around E40-46, the age at which these cells have just established
      their adult lamination and extrinsic afferents have begun to grow into the
      tectum. GABA and CB likely play diverse roles during this stage of development,
      including the regulation of intracellular calcium during cell migration and
      neurite outgrowth. Glutamate is expressed somewhat later in development while
      parvalbumin immunoreactivity does not appear until shortly after birth. These two
      substances continue to increase in density throughout the period of postnatal
      growth, at a time when synapse formation and evoked electrical activity are
      beginning to develop. Both PV and glutamate may be involved in one or both of
      these activity-dependent processes. Nitric oxide synthase (NOS) is expressed at
      different times in different cell groups. NOS appears very early in prenatal
      development in cells within the SVZ and in the deep gray layer of SC. On the
      other hands, cells within the intermediate gray layer of SC do not express NOS
      until shortly before birth. The igl cells that express NOS at this age are
      clustered neurons similar to those that project to the CFR in the adult. NOS
      expression occurs in these cells at precisely the time when axons begin to form
      patches that innervate these clusters. Based upon this temporal correlation, we
      hypothesize that nitric oxide may regulate synapse formation in this cell group.

PMID- 8979812
TI  - Growth cone dynamics and activity-dependent processes in neuronal network
      development.
AB  - Many structural and functional properties of neuronal networks find their origin
      in the dynamic behavior of growth cones during development. The variation in
      dendritic morphologies can be traced back to random branching of growth cones.
      Segment length characteristics arise under random branching and steady growth
      cone propagation. Delayed outgrowth, as a result of competition between growth
      cones after splitting, is hypothesized to explain different lengths of paired
      terminal segments in Purkinje cells. The implications of activity-dependent
      neurite outgrowth were studied using an outgrowth function based on the theory of
      Kater et al. (1988, 1990). This theory embodies a homeostatic principle,
      according to which a neuron adapts its neuritic field so as to maintain a certain
      level bioelectric activity. It is shown that such homeostasis has many
      implications for neuromorphogenesis and network formation, as it may underlie
      phenomena such as overshoot during development, size differences among cells,
      differentiation between excitatory and inhibitory cells and compensatory
      sprouting. Finally, function-dependent regulation of development involves
      physiological as well as morphological variables. For instance, activity
      dependent regulation of ionic conductances such as to stabilize functional
      activity can result in a differentiation of certain neurons into, respectively,
      bursting and regular firing sub-types (Abbot et al., 1993; LeMasson et al.,
      1993). Similarly, the GABAergic phenotype comes fully to expression in hindbrain
      (cerebellar) and forebrain (neocortical) networks only if the level of ongoing
      excitatory activity during development is sufficiently high, whereas chronically
      intensified activity leads to a compensatory hypertrophy of inhibitory mechanisms
      (for review, see Corner 1994). Many of these results could only have been
      obtained by the use of mathematical models which allow rigorous analysis of the
      consequences of basic assumptions in the dynamics of neurite outgrowth. All in
      all, the findings further emphasize the role of spontaneous bioelectric activity
      during early development in neuronal network formation, the importance of which
      was first established in cultures of developing neural tissue.

PMID- 8979814
TI  - Cellular and molecular correlates to plasticity during recovery from injury in
      the developing mammalian brain.
AB  - In summary, our studies indicate that the perinatal mammalian brain shows
      considerable plasticity in response to trauma. Studies carried out both in vivo
      in the perinatal mouse brain and in vitro in cell line culture and organotypic
      slice cultures of developing brain tissue, indicate that the cytokine,
      interleukin-1 beta (IL-1 beta) regulates early healing responses that restore the
      integrity of the damaged structure and create conditions conducive to the
      sprouting of new connections involved in plasticity. In response to a lesion
      placed in the cerebral cortex in a late third trimester embryo, astrocytes form a
      line that delimits damaged tissue being removed by phagocytic macrophages from
      tissue that will remain part of the neural parenchyma. By six days after birth,
      this line of delimiting astrocytes (LDA) appears to become the new glial limiting
      membrane or glial limitans at the lesion site. A gliotic scar covers the new
      glial limitans, but no gliosis appears within the neural parenchyma itself. The
      expression of IL-1 beta is upregulated in astrocytes that form the LDA and is
      also upregulated in the parenchyma internal to the LDA. Experiments done in vivo
      where the type 1 interleukin-1 receptor was blocked via injection of interleukin
      receptor antagonist protein (IL-ra) indicated that both LDA formation and wound
      closure were dependent upon interleukin type 1 receptor activation. To test the
      idea that IL-1 beta could directly influence astrocyte shape and orientation, in
      vitro studies were carried out on astrocytic C6 glioma cells in culture. IL-1
      beta induced changes in cell shape and orientation similar to those seen in in
      vivo formation of the LDA. Addition of IL-1ra blocked IL-1 beta induced changes
      in C6 cells. IL-1 beta, then, acting upon its type 1 receptor, regulates
      astrocytic activities that, in vivo, produce successful healing in the perinatal
      brain. Studies in organotypic slice cultures of early postnatal mouse hippocampus
      parallel in vivo studies. Phagocytic cells, in this case, "reactive/activated"
      microglia, reach peak numbers immediately after injury induced by culture
      preparation. The round microglia were replaced over 10 days in culture by
      "resting/ramified" microglia. Over the first 2 days of culture, astrocytes
      appeared thin and elongated, resembling cells that form the LDA in vivo. Over the
      next 8 days in cultures, astrocytes underwent hypertrophy to form a gliotic scar
      over the surface of the culture. The scar resembled that seen external to the LDA
      after healing in in vivo experiments. IL-1 beta was abundantly expressed
      throughout the culture period by cells showing a variety of morphologies.
      Finally, neurite sprouting, an indicator of circuit reorganization and
      plasticity, occurred rapidly in the hippocampal dentate gyrus in both in vivo and
      in vitro paradigms. A prenatally placed lesion in the entorhinal cortex that
      partially deafferents the developing dentate gyrus, induced novel sprouting of
      the axons of dentate granule cells, the mossy fibers, into the dentate molecular
      layer. Similar sprouting occurred in vitro in organotypic slice culture of
      deafferented hippocampus. In culture, sprouting was first observed at the time of
      onset of astrocyte hypertrophy, indicating that astrocyte derived factors may
      play a role in regulating circuit reorganization. Viewed together, in vivo and in
      vitro studies indicate that IL-1 beta upregulation in neural tissue correlates
      with glial activities that underlie rapid healing and repair in the perinatal
      brain, and that glial activities associated with deafferentation may play a role
      in inducing compensatory neurite sprouting and cicuit reorganization.

PMID- 8979815
TI  - Extensive cortical reorganization following sciatic nerve injury in adult rats
      versus restricted reorganization after neonatal injury: implications for spatial
      and temporal limits on somatosensory plasticity.
AB  - Expansion of the saphenous representation in rat S-I cortex following sciatic
      nerve injury, examined at different times after injury and following injury at
      different developmental stages, has contributed to the beginnings of a
      comprehensive view of spatial and temporal patterns of cortical reorganization.
      In the first few days or weeks after deafferentation in adult animals, cortical
      reorganization may be spatially constrained to convergence zones between central
      representations of peripheral nerves (Wall and Cusick, 1984; Garraghty et al.,
      1994a; Schroeder et al., 1995). The apparent steady state of the rat hindpaw
      system up to 5-6 months after sciatic nerve injury contrasts with the additional,
      nearly complete reorganization shown at times longer than 7-8 months. The late
      reorganization supports the concept that reorganized cortical maps can continue
      to be altered throughout life. The prolonged time course of change in the rat
      hindpaw system suggests that studies of "chronic" nerve injuries need to
      carefully define the reorganizational state of the system at the time intervals
      studied. For humans with peripheral nerve or amputation injuries, the results
      imply that the short term postinjury status can be further altered at longer
      times, perhaps decades later. To characterize the neurochemical consequences or
      mechanisms of cortical reorganization, it is necessary to consider possible
      differences between early versus late changes. Time dependent changes in
      neurotransmitters and their receptors have been described following peripheral
      injury (e.g., Avendano et al., 1995). In addition, both early and late mechanisms
      or consequences of reorganization may differ spatially. In the example of changes
      in rat hindpaw cortex after sciatic nerve transection, neurochemical changes in
      "expansion" cortex may differ quantitatively or qualitatively from changes in the
      deafferented "sciatic dominant" zone. To accurately define neurochemical changes,
      it may thus be necessary to characterize sample zones as having intact or
      reorganized inputs, or as deprived of inputs. The studies of cortical
      reorganization following neonatal sciatic nerve injury underscore the importance
      of developmental age at time of injury. Most studies of critical periods in the
      central nervous system have emphasized greater plasticity in developing as
      opposed to adult animals. Early lesions or deprivation, however, not only result
      in connectional alterations, but can produce dramatically more atrophy or cell
      loss (e.g., see Cunningham, 1982; Waite, 1984; Himes and Tessler, 1989). A number
      of authors have commented on the seeming paradox of greater transneuronal and
      retrograde cell death, yet greater neuronal plasticity, in infant animals. How
      developmental stage influences plastic responses to peripheral injury in the
      somatosensory system is not completely understood. Early peripheral lesions may
      deprive central neurons of necessary trophic factors, accentuate naturally
      occurring central cell death, and thereby result in smaller central
      representations. Or, smaller central representations may be produced by
      competitive interactions of deprived with adjacent intact pathways. In addition,
      throughout all stages of development, the capacity for reorganization may be
      spatially limited and depend on the size or pattern of the peripheral injury.

PMID- 8979813
TI  - The subependymal zone: "brain marrow".
AB  - From all of the studies of developmentally regulated molecules as well as the
      impressive proliferation of cells within the SEZ, we would like to propose that
      the SEZ of the adult brain, from the lateral ventricles of the cerebrum to the
      central canal of the spinal cord, represents a potential "brain marrow" from
      which stem and progenitor cells can be further studied and exploited for cell
      replacement and circuitry repair paradigms for neurological disease. Without
      question the SEZ is not as regenerative or pleuripotential as bone marrow or
      other hematopoietic systems, but there are definitely some elements in common.
      Bone marrow contains a pleuripotent stem cell that under certain conditions (e.g.
      the presence of certain growth factors and cytokines) gives rise to erythroblasts
      and myeloblasts whose progeny include erythrocytes, monocytes, thrombocytes and
      macrophages. Different growth factors can likewise affect the proliferation as
      well as differentiation of adult CNS stem and progenitor cells, again
      contributing to diverse cellular phenotypes. The roles for matrix molecules in
      these events are yet to be discovered, however, there is evidence to suggest that
      matrix molecules, including tenascin, do interact with hematopoietic stem cells
      (Yoder and Williams, 1995) to possibly affect their proliferation and
      differentiation. Future studies might reveal a similar role for the dense ECM
      expression within the SEZ proliferative/migratory pathway.

PMID- 8979816
TI  - Neural plasticity after brain damage.

PMID- 8979817
TI  - Neural mechanisms of visual orienting responses.

PMID- 8979818
TI  - The mosaic architecture of the superior colliculus.
AB  - The superior colliculus is a midbrain structure serving visual, multisensory and
      sensorimotor processing. Throughout various collicular layers, visual afferents
      are linked together with afferents related to other sensory modalities as well as
      with afferents from sources not easily subsumed under the term 'sensory'. These
      inputs are orchestrated in a topographic fashion and led to premotor neurons that
      are important elements in generating saccadic eye movements and orientation
      movements of other kinds. Using immunocytochemical techniques to chart the
      distribution of various substances serving neurotransmission and neuromodulation,
      it was found that many of them, e.g. acetylcholinesterase (AChE), choline
      acetyltransferase, the enkephalins, substance P, and parvalbumin, relate to
      repetitive structural islands, or modules, in the superior colliculus. From
      studies on the distribution of three further neuroactive substances in rat
      superior collicular tissue: the calcium binding protein calretinin, the growth
      and plasticity related protein neuromodulin (GAP-43), and a glutamate receptor of
      the NMDA-type, we were led to conclude (1) that the intermediate layers of the
      superior colliculus are composed not of two, but of at least three disjunct types
      of modules, (2) that not just the intermediate layers but more or less the whole
      superior colliculus is an assemblage of modules, and (3) that, besides
      topographic connectivity and laminar structuring, the modules constituting an
      iterative partitioning represent a third major feature of superior collicular
      architecture. The origin of the collicular mosaic is considered under an
      evolutionary perspective, and a hypothesis is presented stating that the pattern
      of AChE-rich modules on the level of the multimodal collicular layers can be
      predicted from retinal ganglion cell topography.

PMID- 8979819
TI  - Neurochemical microcircuitry underlying visual and oculomotor function in the cat
      superior colliculus.
AB  - The cat superior colliculus (SC) plays an important role in visual and oculomotor
      functions, including the initiation of saccadic eye movements. We have studied
      the organization of neurochemical specific circuits in SC that underly these
      functions. In this chapter we have reviewed three microcircuits that can be
      identified by cell type, chemical content, and synaptic input from specific
      afferents. The first is located within the upper sgl and is related to the W
      retinal pathway to this region of SC. This circuit includes relay and
      interneurons that contain the calcium binding protein calbindin (CB), GABA
      containing presynaptic dendrites, and retinal terminals that have a distribution
      and size typical of W retinal terminals in the cat SC. This circuit is a typical
      synaptic triad that mediates feedforward inhibition, possibly to regulate outflow
      of the W pathway to the lateral geniculate nucleus. CB neurons in SC and other
      structures may be uniquely related to low threshold calcium currents in these
      neurons. The second microcircuit consists of neurons that contain parvalbumin
      (PV), another calcium binding protein. These neurons are located in a dense tier
      with the deep sgl and upper ol and they receive input from retinal terminals that
      are likely from 'Y' retinal ganglion cells. Some of these neurons also project to
      the lateral posterior nucleus and some colocalize glutamate. We speculate that
      these neurons also receive cortical 'Y' input although we have yet to prove this
      experimentally. The role of PV in these cells is unknown, but PV has been shown
      to be contained in fast spiking, non-accomodating neurons in visual cortex which
      have very rapid spike discharges that are also characteristic of SC neurons
      innervated by 'Y' input. The third microcircuit consists of a group of clustered
      neurons within the igl of the cat SC that overlaps the patch-like innervation of
      afferents to this region that come from the pedunculopontine tegmental and
      lateral dorsal tegmental nuclie, the substantia nigra, and the cortical frontal
      eye fields. These clustered neurons project through the tectopontobulbar pathway
      and terminate within the cuneiform region (CFR) of the midbrain tegmentum. They
      transiently express NOS during development. Ongoing studies in our laboratory
      suggest that these cells receive synaptic inputs directly from the PPTN and SN
      and may represent functional modules involved in the initiation of saccadic eye
      movements.

PMID- 8979820
TI  - Serotonin modulates retinotectal and corticotectal convergence in the superior
      colliculus.
AB  - A dense serotonin (5-HT)-containing projection to the superficial layers of the
      superior colliculus (SC) has been demonstrated in diverse mammalian species, but
      how 5-HT may affect visual signals within these laminae is largely unknown. This
      study undertook to investigate the distribution of 2 types of 5-HT receptors in
      the SC and to ascertain their physiological effects on transmission of visual
      signals to the SC from the retinotectal and corticotectual pathways.
      Autoradiography of tissue sections exposed to [3H]-8-OH-DPAT (8-hydroxy
      dipropylaminotetraline) or to [125I]cyanopindolol plus isoproterenol showed that
      5-HT1A and 5-HT1B receptors, respectively, were present in the superficial SC
      layers. In unilaterally enucleated animals, binding of ligand to 5-HT1B receptors
      was greatly reduced on the deafferented (contralateral) side, which is consistent
      with the possibility that these receptors are located on preterminal axons.
      Binding to 5-HT1A receptors was unaltered by enucleation. In recordings of
      superficial layer neurons from SC slices, application of 5-HT during blockade of
      5-HT1A receptors with spiperone reduced the amplitude of EPSPs evoked by
      stimulation of the optic tract. The 5-HT concentration for a 50% reduction in
      EPSP amplitude was 6 microM. Under these conditions, there were no significant
      alterations in either membrane potential or input resistance concurrent with 5-HT
      mediated reduction in EPSPs. During extracellular in vivo recordings, 5-HT,
      applied by iontophoresis or micropressure or by endogenous release produced by
      electrical stimulation of the dorsal raphe nucleus, strongly suppressed visual
      activity in SC neurons. The effectiveness of 5-HT application was significantly
      stronger on responses evoked by electrical stimulation of the optic chiasm (an
      average response decrement of 92.2%) than on these evoked in the same neurons by
      stimulation of visual cortex (an average response reduction of 32.3%). These
      results support the following conclusions. The 5-HT1B receptors are located
      preferentially on optic axon terminals and exert presynaptic inhibition of
      retinotectal inputs. Secondly, 5-HT1A receptors probably have a postsynaptic
      localization and may affect activity of SC neurons irrespective of the source of
      input. The combined effect of 5-HT at both subtypes would bias SC visual activity
      toward information received from the corticotectal pathway.

PMID- 8979821
TI  - Morphology of single axons of tectospinal and reticulospinal neurons in the upper
      cervical spinal cord.
AB  - Single axons of tectospinal (TS) and reticulospinal (RS) neurons were stained
      with intraaxonal injection of HRP after electrophysiological identification, and
      their axonal trajectory was reconstructed at C1-C3 of the cat. TS neurons were
      located in the intermediate or deep layers of the caudal two-thirds of the
      superior colliculus (SC) and had multiple axon collaterals (up to seven
      collaterals) per stem axon). Collaterals had a simple structure, ramified several
      times mainly in the transverse plane, and terminated in the lateral parts of
      laminae V-VIII. More than half also had terminals in lamina IX. Terminals of TS
      neurons did not appear to make contacts with either the somas or proximal
      dendrites of retrogradely-labeled motoneurons in lamina IX, but clear contacts
      were found on counterstained interneurons in the lateral part of laminae V-VIII.
      Here, we examined three stained spinal interneurons receiving monosynaptic
      excitation from the SC. These interneurons had multiple axon collaterals mainly
      in laminae VII-IX, and made extensive contacts with retrogradely-labeled
      motoneurons of multiple neck muscles. Stem axons of single RS neurons receiving
      input from the contralateral SC ran in the ventromedial funiculus and gave off
      multiple axon collaterals to laminae VII-IX over at least several cervical
      segments. Their terminal boutons appeared to make contact with both the somas and
      proximal dendrites of retrogradely-labeled neck motoneurons. Single RS neurons
      made contacts with motoneurons of different neck muscles. These results provide
      evidence for functional synergies at the level of single RS neurons and spinal
      interneurons for neck movements. The present finding indicates that the direct TS
      projection to the spinal cord may influence the activity of multiple neck muscles
      mainly via spinal interneurons, and plays an important role in control of head
      movement in parallel with the tecto-reticulospinal system.

PMID- 8979822
TI  - A projection linking motor cortex with the LM-suprageniculate nuclear complex
      through the periaqueductal gray area which surrounds the nucleus of
      Darkschewitsch in the cat.
AB  - Whereas a previous study by one of us (Hicks et al., 1986) suggested that
      periaqueductal gray (PAG) neurons projecting to the lateralis medialis
      suprageniculate (LM-SG) complex might mediate transmission of affective-related
      nociceptive information, our present work suggests instead, a function in
      processes related to movement. Cells of the nucleus of Darkschewitsch (ND) are
      known to have reciprocal projections with the motor cortex (MX), in particular
      with the hand area of MX, and also to project to the rostral medial accessory
      olivary (MAO) nucleus (Onodera and Hicks, 1995a). That the ND might be related to
      saccadic oculomotor function, as well as to the control of hand movements through
      its connections via the olivo-cerebellar circuit, is indicated by the fact that
      ND receives a strong projection from the substantia nigra pars reticulata and
      zona incerta (SNR/ZI) and projects directly and/or indirectly to eye movement
      nuclei (Onodera and Hicks, 1995b). Thus, ND may function in permitting
      integration of eye-hand motor coordination. This study focussed on the area of
      PAG surrounding ND. WGA-HRP was injected into MX and many labelled terminals and
      large neurones were in ND, with lesser numbers being observed in the area of the
      PAG surrounding ND. After injections into ND and closely adjacent areas, labelled
      terminals were observed sparsely distributed with a restricted area of the LM-SG
      complex. After injections into LM-SG area, small neuronal somata were seen in the
      area of the PAG surrounding ND, but no labelled somata were detected in ND. Thus
      if the cells of this PAG area, like those of ND, have similar functions owing to
      their common reciprocal connections with MX, then the small neurones in PAG
      projecting to LM-SG may constitute an important link in the circuitry subserving
      visual processing and/or the regulation of orienting movements of the hand, head
      and eye.

PMID- 8979823
TI  - Firing characteristics of neurones in the superior colliculus and the
      pontomedullary reticular formation during orienting in unrestrained cats.
AB  - Cats were trained to fixate a center LED or light spot for 1-10 s and to orient
      to a target (LED or light spot), which appeared simultaneous with the
      disappearance of the fixation light. Firing characteristics of neurones in the
      superior colliculus (SC) and the pontomedullary reticular formation were examined
      systematically in cats performing the above orienting task. In the head-free
      condition, a majority of the superficial neurones in the SC was activated when a
      target appeared in a particular area in the visual field (receptive field) as in
      head fixed animals. We identified a new group of neurones in superficial layers
      of the SC, superficial fixation neurones, which fired tonically when fixated on a
      target light with little activity at fixating a center fixation light. In the
      intermediate and deep layers of the SC, many neurones fired when directed to a
      particular area in the visual field (movement field). In addition to these
      neurones, we found new groups of neurones fired tonically in a particular phase
      of orienting. These neurones were divided into three principal types, target
      activated, target suppressed and center fixation activated neurones. Target
      activated neurones fired tonically during the fixation of a target, but not
      during fixation of a center spot. Target suppressed neurones were characterized
      by a pause during fixation of targets irrespective of their location. They had
      clear phasic and tonic components. The phasic component was characterized by a
      movement field resembling that seen in a typical intermediate layer neurone.
      Center fixation activated neurones discharged during fixation of the center spot
      and exhibited suppression during fixation of the target. Many neurones in the
      pontomedullary reticular formation fired during orienting. Four major types of
      neurones, phasic, phasic sustained, pause and tonic neurones, were differentiated
      on the basis of their firing patterns. Phasic units were characterized by brief
      phasic firing during orienting and could be divided into four subtypes. Long lead
      phasic neurones began to fire 50-100 ms prior to the onset of a gaze shift and
      stopped well before the end of the gaze shift and the total number of firing was
      best correlated with the total angle of head rotation. Short lead phasic neurones
      started to fire 10-20 ms prior to a gaze shift and were further subdivided into
      decrement and plateau types. The decrement type exhibited a brief burst just
      prior to gaze shift and stopped discharging prior to the end of the gaze shift,
      while the plateau type fired tonically during the gaze shift and stopped firing
      after the gaze shift. Total number of discharges of both type was related to
      maximal angular velocity. The fourth type, gaze neurone, began firing coincident
      with the onset of the gaze shift and stopped firing at the completion of the gaze
      shift and the total number of discharges was closely related to total angle of
      head rotation Phasic sustained (PS) neurones fired 50-100 ms before the onset of
      a gaze shift and their discharges continued after the end of the gaze shift and
      were divided into three subtypes: augmenting, pause and plateau. The augmenting
      type was characterized by a transient increase of firing during the gaze shift
      and a maintained slow rate of firing following the gaze shift. Total number of
      discharges related to head movement amplitude and the sustained activity was
      correlated with head position. The pause type was suppressed during the gaze
      shift and was tonically active during a head movement. The plateau type had a
      weak phasic component and discharged at a fairly constant rate. The pause and
      plateau types appeared to be related to head amplitude and head position,
      respectively. Tonic units were classified into several types. Target fixation
      neurones exhibited sustained firing when the cat was fixating a target,
      irrespective of its location, but did not show sustained firing when the animal
      fixated the fixation light. Fixation neurones fired tonical

PMID- 8979824
TI  - Ibotenic acid lesions of the superior colliculus produce longer lasting deficits
      in visual orienting behavior than aspiration lesions in the cat.
AB  - We compared the effects of unilateral surgical aspiration and ibotenic acid
      produced lesions of the superior colliculus (SC) on visual orienting behavior in
      20 cats. Four animals with aspiration lesions initially showed an hemianopia in
      the contralateral hemifield which recovered fully in 4.5 weeks or less. These
      lesions also destroyed axons in the commissure of the superior colliculus (CS).
      In 9 animals we produced complete loss of cells in one SC, with preservation of
      axons in the CSC, by injections of ibotenic acid. In these animals the
      contralateral hemianopia persisted for an average of 16.6 weeks, but may have
      persisted longer had we not intervened by either sacrificing the animal or
      ablating the visual cortex contralateral to the SC lesion. The cortical lesion
      produced an immediate hemianopia in the contralateral hemifield and a recovery in
      the previously hemianopic ('collicular') hemifield. In the remaining 7 animals
      with attempted ibotenic acid lesions, 5 had incomplete lesions and 2 others
      sustained major damage to the SC as well as the CSC. These 7 animals recovered
      visual orienting on an average of 3.0 weeks postoperatively. We conclude that
      unilateral loss of collicular cell function and the presence of fibers coursing
      through the commissure of the superior colliculus are both necessary for the
      prolonged deficit in visual orienting behavior. We suggest that competition
      between the two hemifields may play a role in the hemianopia caused by collicular
      manipulations and that the cholinergic pathway from the pedunculopontine nucleus
      to the contralateral SC via the CSC may be involved.

PMID- 8979825
TI  - Spatial distribution of tectotectal connections in the cat.
AB  - In mammals, the paired superior colliculi of the midbrain play a significant role
      in the generation and guidance of eye movements that enable an animal to orient
      to novel visual stimuli. In several species including monkey, cat and hamster,
      the paired colliculi are connected by a commissure. In the cat, many commissural
      axons arise from tectotectal neurons located in the deep layers in the rostral
      two-thirds of the colliculus. The role of these tectotectal neurons is unclear,
      but it is likely that they play some role in eye movement control. In this study,
      the neuroanatomical tracer Biocytin was used to make small, localized injections
      into the deep layers of the cat superior colliculus at a variety of different
      locations in nine animals. The distribution of tectotectal synaptic terminals in
      the opposite colliculus was then plotted. Regardless of which layers were
      included the injection site, labelled boutons were most dense in the deep layers
      in the contralateral colliculus. There was a striking point-to-point organization
      in the tectotectal projection such that terminals were concentrated at an almost
      mirror-symmetrical region to the injection site in the rostrocaudal plane. In the
      majority of cases, however, the focus of terminal boutons was shifted medially by
      1-2 mm. These results suggest that tectotectal connections may influence select
      populations of neurons in the contralateral colliculus. By coupling specific
      groups of neurons in the two colliculi, their effectiveness in sensory motor
      processing could be enhanced. At this time it is not clear whether specific
      commissural terminals contain excitatory or inhibitory neurotransmitters, and our
      ongoing studies are addressing this question.

PMID- 8979826
TI  - Roles of the lateral suprasylvian cortex in convergence eye movement in cats.
AB  - Ocular convergence and lens accomodation were evoked by microstimulation in the
      lateral suprasylvian area (LS cortex) in the parieto-occipital cortex in the cat.
      Electrolytic lesions in LS cortex reduced the amplitude and velocity of ocular
      convergence. Neurons in LS cortex discharged in relation to ocular convergence
      and/or lens accommodation. These results support the hypothesis that the LS
      cortex plays an important role in controlling ocular convergence The LS cortex
      receives visual inputs from cortical visual areas 17, 18 and 19, and in addition
      from the superior colliculus through the LP nucleus of the thalamus.
      Electrophysiological recordings have revealed that these visual inputs, which
      include cues about 3-dimensional target motion, are integrated in the LS cortex.
      The integrated output from LS cortex may provide the brainstem motor centers with
      the neural signals that facilitate eye movements, especially when the target is
      moving at high speeds. Outputs from the LS cortex travel directly to brainstem
      structures including the superior colliculus and pretectum. Evidence from monkey
      suggests that information may also travel to the mesencephalic reticular
      formation, where neurons have been recorded that are related to ocular
      convergence, lens accomodation or both. Although comparable data is lacking in
      the cat, it is suggested that the efferent circuit from the LS cortex to the
      motor nuclei in the brainstem included both the superior colliculus and the
      mesencephalic reticular formation. It is also suggested that this pathway is
      rather short, given that the mean latency of the early component of evoked
      disjunctive eye movements was approximately 60 ms.

PMID- 8979827
TI  - Functional connectivity of the superior colliculus with saccade-related brain
      stem neurons in the cat.
AB  - Effects of stimulation of the superior colliculus on saccade-related brain stem
      neurons were studied in the alert cat. Extracellular recordings were made from
      medium-lead burst neurons (MLBNs), omnipause neurons (OPNs) and burster-driving
      neurons (BDNs) in the paramedian pontomedullary region rostral and caudal to the
      abducens nucleus. MLBNs were activated from the contralateral superior colliculus
      with monosynaptic latencies when single-pulse stimulation was given during
      saccades or ipsilateral head rotation, although this activation was not observed
      during fixation periods. The caudal SC was more effective than the rostral SC in
      monosynaptic activation of MLBNs. Most OPNs were also activated monosynaptically
      from the SC. In contrast to MLBNs, the activation of OPNs was more frequently
      induced from the rostral SC than from the caudal SC. Stimulation of the caudal SC
      often induced suppression of spikes in OPNs. BDNs received excitation from the
      ipsilateral SC through a di- or trisynaptic pathway. Like MLBNs, BDNs tended to
      receive stronger input from the caudal SC than the rostral SC. Results indicate
      the existence of tectofugal excitatory pathways to MLBNs and BDNs and an
      inhibitory pathway to OPNs. It seems likely that these pathways originate from
      saccade-related burst cells in the SC. Since excitation of BDNs and inhibition of
      OPNs increase the excitability of MLBNs, all of these pathways may contribute to
      burst activity in MLBNs and thereby saccade generation. Results also support the
      current idea that cells in the rostral SC may participate in fixation by
      activating OPNs.

PMID- 8979828
TI  - Visual-auditory integration in cat superior colliculus: implications for neuronal
      control of the orienting response.
AB  - Previous physiological studies have demonstrated that inputs from different
      sensory modalities converge on individual neurons in the superior colliculus.
      Moreover, in anesthetized, paralyzed animals, those tectal neurons which are most
      directly connected to brain stem circuits mediating orienting eye and head
      movements are highly likely to exhibit significant integration of sensory inputs
      from multiple modalities. The purpose of the present study was to examine the
      responses of tectal neurons in the alert cat when visual and auditory stimuli
      were presented as targets for ocular fixation and orienting responses. For
      comparison to previous work in anesthetized, paralyzed animals, we also examined
      the responses of tectal neurons to the presentation of these stimuli during
      periods when the cats voluntarily maintained their eyes near primary position in
      the absence of a fixation target. Under these conditions, there were significant
      differences between the strength of the response to the simultaneous presentation
      of visual and auditory targets and the strength of response to the most effective
      unimodal stimulus in about 40% of the cells tested. Many tectal neurons also
      responded tonically during fixation of visual, auditory and bimodal targets, and
      some of these also exhibited significant bimodal interactions. However, among
      individual neurons which responded phasically to stimulus onset or offset and
      tonically during fixation, there was only a weak correlation between the extent
      of bimodal interaction under the two conditions. Finally, among saccade-related
      neurons, the magnitude of saccade-related activity was only slightly affected
      when a biomodal target was used to elicit a saccade, and the extent of bimodal
      interactions was generally less than was found for the onset and offset of
      sensory targets. Such multisensory interactions can be significant for behavior.
      Indeed, simply using a multisensory target has been shown to influence the
      probability and latency of overt orienting responses, although the extent of such
      effects will probably vary across both tasks and stimulus conditions. Strong
      multi-sensory interactions are most likely to occur when low intensity stimuli
      are used. Our use of moderately intense sensory stimuli probably accounts for our
      finding of a relatively small percentage of cells in which bimodal responses were
      greater than the sum of their unimodal responses.

PMID- 8979829
TI  - Task-dependence of saccade-related activity in monkey superior solliculus:
      implications for models of the saccadic system.
AB  - Current models assign a crucial role to the deep layers of the Superior
      Colliculus (SC) in the dynamic feedback control of saccadic eye movements.
      However, if the SC is to be part of the local feedback loop for saccades, it is
      expected that the movement-related firing patterns of deep layer SC cell maintain
      a fixed relation with the instantaneous saccade trajectory, regardless of the
      conditions that evoked the saccade. In this paper we provide three different
      lines of evidence, suggesting that the movement activity of SC burst cells may
      change as a function of the sensory conditions evoking the saccade. First, it is
      shown that bimodal (visual-auditory) stimulation may markedly enhance (up to
      about 350%) or suppress (on average down to 70%) SC motor bursts when compared to
      the activity for unimodal visual stimulation. Second, the movement activity
      associated with auditory-evoked saccades appeared to be reduced by almost 60%
      relative to visually-evoked saccades of the same metrics (tested in one monkey).
      However, for both paradigms, these relatively large changes in movement activity
      went without a concomitant change in the saccade properties. Third, a short-term
      saccadic adaptation paradigm produced saccades with a smaller amplitude (gain
      about 0.7) upon presentation of the adapting visual stimulus. However, we found
      that the movement-related activity of SC burst cells did not change in this
      paradigm. These findings suggest that the SC cells do neither encode saccade
      kinematics, nor the precise components of the saccade vector. Rather, we propose
      that the motor SC issues a crude desired eye displacement signal to the brainstem
      that is transformed into the appropriate movement signals by downstream or
      parallel mechanisms.

PMID- 8979830
TI  - Coding of stimulus invariances by inferior temporal neurons.
AB  - Primates are able to recognize a particular object despite major differences in
      the retinal images of the object. Inferior temporal cortex is suggested to be
      involved in this invariant object recognition. Neurons of this cortex show shape
      selectivity and it has been shown that this shape selectivity is relatively
      invariant for changes in the position and size of the shape. We show that macaque
      inferior temporal cortical neurons may respond to shapes that are defined by
      relative motion or by texture differences. The degree of shape selectivity can
      vary for the different visual cues, but overall shape preference is invariant for
      shapes defined either by luminance, by relative motion or by texture. Also, we
      found that shape selective inferior temporal neurons respond to partial occluded
      shapes and that their shape selectivity is similar with and without the partial
      occlusion. These results suggest that inferior temporal neurons, as a population,
      can code for an abstract, stimulus invariant shape or object part.

PMID- 8979831
TI  - Theories of visual cortex organization in primates: areas of the third level.
AB  - This brief review has a few main points. (1) Early proposals on how extrastriate
      cortex is subdivided were inconsistent with each other, and differences in
      interpretation were not resolved. (2) Brodmann's proposal of two ring-like areas,
      18 and 19, surrounding primary visual cortex gained great acceptance despite the
      lack of agreement among different investigators considering the same evidence.
      (3) The concepts of areas 18 and 19, transposed to signify V2 and V3, have had
      great impact on recent and even current theories of extrastriate visual cortex
      organization in primates. (4) Nevertheless, Brodmann's areas 18 and 19, as
      defined in humans and Old World monkeys, correspond to none of the fields
      currently proposed for these primates. (5) All or most mammals appear to have a
      V2, and there is now widespread complete agreement over the extent and
      organization of this area in all studied primates. V2 is commonly referred to as
      area 18 because of its correspondence to area 18 as defined by Brodmann is some
      mammals. Yet, we should recognize that V2 is about half the size of Brodmann's
      area 18 in Old World monkeys and humans. (6) Current concepts of V3 differ
      greatly from the ring-like area 19 of Brodmann. We question the validity and
      usefulness of retaining the concept of V3 in primates. Our proposal for DM and
      other visual areas along the outer border of V2 seems more consistent, not only
      with the evidence from New World monkeys, but with evidence from Old World and
      prosimian primates, and even mammals most closely related to primates (see Kaas
      and Preuss, 1993). In all of these primates and close relatives of primates, the
      evidence indicates that more than one field forms the outer border of V2.

PMID- 8979832
TI  - Afferent and developmentally inherent mechanisms of form and motion processing in
      cat extrastriate cortex.

PMID- 8979833
TI  - Extrinsic and intrinsic connections of the cat's lateral suprasylvian visual
      area.
AB  - The lateral suprasylvian visual area (LS) is known to have numerous
      interconnections with visual cortical areas as well as with subcortical
      structures implicated in visually-guided behaviors. In contrast, little data is
      available regarding connections within the LS itself. In order to obtain
      information about intra-areal connections and to re-investigate LS connectivity
      with various cortical and subcortical areas, the traces (biocytin or WGA-HRP) was
      injected into various loci along the medial and lateral banks of the LS. The
      anterograde tracer, biocytin injections into both medial and lateral bank
      produced label contained within the respective bank that extended rostrally and
      caudally from the infection site. In addition, following medical bank injections,
      considerable label was distributed throughout the fundus and, to a lesser extent,
      in the lateral bank. In contrast, no label could be detected in the medial bank
      after lateral bank injections, and, although label was observed in the fundus, it
      was restricted to the most lateral aspects. Moderate labeling could be observed
      in the medial bank following the tracer injection into the most rostral aspect of
      the lateral bank. It is likely that input derived from various visual cortical
      areas which project to the medial bank of the LS has access to this intra-areal
      circuitry. This may provide a route by which visual cortical information can be
      relayed to other cortical and subcortical structures involved in visually-guided
      behaviors such as the anterior ectosylvian visual cortex, striatum, and the deep
      layers of the superior colliculus, despite the fact that these structures
      themselves do not receive substantial direct projections from the visual cortical
      areas that are associated with the medial bank. Examination of the laminar
      location of the cells-of-origin of striate and extrastriate projections to LS
      using retrograde trace, WGA-HRP, revealed that the supragranular laminae of areas
      17, 18 and 19 were the source of LS afferents whereas afferents from the other
      cortical areas (e.g., 20a, 20b, 21a, 21b, 7 and anterior ectosylvian visual area)
      were from both supra- and infragranular laminae. In addition, all LS subregions
      received intra-areal afferent projections from all LS cortical laminae. Thus,
      although rather clear hierarchical relationship between LS and visual cortical
      areas appears to exist, the interconnections among LS subregions provide no clear
      evidence of simple hierarchical relationships between regions LS or may have feed
      forward and feed-back pathways.

PMID- 8979834
TI  - Areas PMLS and 21a of cat visual cortex are not only functionally but also
      hodologically distinct.
AB  - In several cats, paired visuotopically matched injections of retrogradely
      transported fluorescent dyes, diamidino yellow (DY) and fast blue (FB), were made
      into two visuotopically organized, functionally distinct extrastriate cortical
      areas, the posteromedial lateral suprasylvian area (PMLS area) and area 21a
      respectively. After an appropriate survival time, the numbers of thalamic,
      claustral and cortical cells which were single-labelled with each dye as well as
      the numbers of cells in these structures labelled with both dyes (double-labelled
      cells) were assessed. The clear majorities of thalamic cells projecting to PMLS
      area (DY labelled cells) and to area 21a (FB labelled cells) were located in the
      ipsilateral lateral posterior-pulvinar complex with smaller proportions located
      in the laminae C and the medial intralaminar nucleus of the ipsilateral dorsal
      lateral geniculate nucleus and several nuclei of the rostral intralaminar
      thalamic group. Despite the fact that DY labelled (PMLS-projecting) and FB
      labelled (area 21 a-projecting) cells in all thalamic nuclei were well
      intermingled, only 1-5% of retrogradely labelled thalamic cells projected to both
      areas (cells double-labelled with both dyes). Small proportions of retrogradely
      labelled cells were located in the ipsilateral and to a lesser extent the
      contralateral dorsocaudal claustra. The proportions of claustral neurons
      retrogradely labelled with both dyes varied from 4 to 9%. Over half of the
      cortical neurons labelled retrogradely from area 21a or PMLS area were located in
      the supragranular layers of the ipsilateral area 17, with smaller proportions
      located in the supragranular layers of the ipsilateral areas 18 and 19 and even
      smaller proportions located in mainly but not exclusively, the infragranular
      layers of the ipsilateral areas 21b and 20a. Again despite strong spatial
      intermingling of neurons labelled with DY and these labelled with FB, the
      proportions of associational cortical neurons double-labelled with both dyes were
      small (2 to 5.5%). Finally, small proportions of neurons retrogradely labelled
      with DY or FB were located, mainly but not exclusively, in the supragranular
      layers of the contralateral areas 17, 18, 19 and 21a. Again, the proportions of
      the double-labelled neurons in the contralateral cortices were small (1-4.5%).
      Thus, the present study indicates that despite the fact that the diencephalic and
      telencephalic inputs to the visuotopically corresponding parts of area 21a and
      PMLS area originate from the same nuclei, areas and layers, the two areas receive
      their afferents from the largely separate populations of neurons.

PMID- 8979835
TI  - Motion sensitivity and stimulus interactions in the striate-recipient zone of the
      cat's lateral posterior-pulvinar complex.
AB  - The cat's lateral posterior-pulvinar complex (LP-pulvinar) establishes reciprocal
      connections with the anterior ectosylvian visual (AEV) and lateral suprasylvian
      (LS) cortices; two regions which are believed to be involved in motion analysis.
      We have investigated the motion sensitivity of neurons in the LP-pulvinar complex
      by: (1) studying the responses properties of cells in the striate-recipient zone
      of the LP nucleus (LPI) to the drift of a two-dimensional texture pattern (visual
      noise); and (2) determining the extent to which the latter stimulus can modify
      the spatial frequency tuning function of LPI cells. Experiments were carried out
      on anesthetized normal adult cats. Almost all LPI cells (55 out of 63, 87%)
      responded to the motion of visual noise. For most units (39 out of 55, 71%),
      responses varied as a function of the direction of motion (bandwidth of 49
      degrees). One-third of the LPI units did not exhibit any preference for drift
      direction of noise. For practically all LPI cells, responses to noise varied as a
      function of drift velocity. Optimal velocities were distributed from 2 to 35
      degrees/s with a mean value of 27.5 degrees/s (means bandwidth of 2.5 octaves).
      The influence of visual noise on the spatial frequency tuning function of 22 LPI
      cells was also studied. For half of LPI cells, responses at all spatial
      frequencies were reduced when the grating and the texture pattern were moving in
      opposite directions (anti phase condition). This masking effect of noise was
      rarely observed when both stimuli were drifted in the same direction (in phase
      condition). These results suggest that the LP-pulvinar complex may be part of
      extrageniculate pathways involved in the analysis of motion of visual targets
      and/or the analysis of the relative movement between an object and its
      surrounding environment.

PMID- 8979836
TI  - Comparisons of cross-modality integration in midbrain and cortex.
AB  - Multisensory neurons are abundant in the superior colliculus and anterior
      ectosylvian cortex of the cat. Despite the fact that these areas receive inputs
      from different regions, and are likely to be involved in different functional
      roles, there multisensory neurons have many fundamental similarities. They all
      have multiple receptive fields, one for each sensory input, and these receptive
      fields overlap one another. It is this spatial correspondence among receptive
      fields that determines the manner in which both populations of neurons integrate
      the inputs they receive from different sensory channels. Several principles of
      integration characterize both cortical and midbrain multisensory neurons, and
      these constancies in the fundamentals of cross-modality integration are likely to
      provide a basis for coherence at different levels of the neuraxis. Yet there are
      also obvious differences in these populations of multisensory neurons. Cortical
      receptive fields are significantly larger than those in the midbrain, have a
      lower incidence of suppressive surrounds, and exhibit less cross-modality
      inhibitory interactions than in the midbrain. Presumably, these differences
      reflect a greater emphasis on non-spatial aspects of cross-modality integration
      in cortex than is required by the orientation and localization functions mediated
      by the superior colliculus.

PMID- 8979837
TI  - Sensory organization of the superior colliculus in cat and monkey.
AB  - The sensory representations and response properties of neurons in the
      multisensory layers of the superior colliculus (SC) of the cat and monkey are
      strikingly similar. In both species, significant numbers of unimodal visual,
      auditory, and somatosensory neurons are intermixed, and share modality-specific
      stimulus selectivities. In addition, these neurons have receptive fields that are
      organized in similar map-like representations, with the different maps sharing
      the same axes and, thus, exhibiting a characteristic cross-modality
      correspondence. Both species also have a large contingent of multisensory neurons
      that synthesize information from different sensory modalities using a common set
      of spatial, temporal, and physical principles. These findings suggest that,
      despite differences in the ontogeny and behavioral repertoires of cat and monkey,
      there is a substantial conservation in the organization and functional properties
      of SC neurons. Apparently, these functional features of the SC are adaptive in a
      wide variety of ecological situations.

PMID- 8979838
TI  - Substitution of visual by auditory inputs in the cat's anterior ectosylvian
      cortex.
AB  - Long-term visual deprivation from birth leads to reorganization of the anterior
      ectosylvian region of the cat's cortex. A visual area in the fundus of AES, area
      AEV, in which neurons normally respond briskly to visual stimuli, is taken over
      almost completely by auditory and somatosensory inputs. Auditory neurons are
      sharply tuned to the location of a sound source in azimuth. A higher than normal
      proportion of neurons in the AES of visually deprived cats responds to multimodal
      stimuli. Takeover of visual regions by non-visual inputs can be explained by the
      same mechanisms that are invoked for developmental plasticity within the visual
      system: neural activity and competition between different inputs leads to changes
      in synaptic efficacy. Additional sprouting cannot be excluded. The radical
      changes of sensory modality within the AEs, caused by visual deprivation, suggest
      that the same code is used by visual, auditory and somatosensory maps in this
      region to represent the sensory environment and lead to sensorimotor
      transformation.

PMID- 8979839
TI  - Visual, somatosensory and auditory modality properties along the feline
      suprageniculate-anterior ectosylvian sulcus/insular pathway.
AB  - Physiological properties of single units were investigated in the suprageniculate
      nucleus (SG) and in the cerebral cortex along the anterior ectosylvian sulcus
      (AES), including the insular cortex. The recording was performed with the aid of
      carbon-filled glass micropipetts in barbiturate-anesthetized cats. The main
      findings of the study can be summarized as follows. 1. The physiological
      properties of the cells in the suprageniculate nucleus and in the AES/insular
      cortex exhibited striking similarities in a series of aspects: (a) The
      frequencies of occurrence of uni-, bi- and trimodal cells were similar. (b) The
      majority of the unimodal cells (75% in the AES/insular region and 65% in the SG)
      has visual sensitivity in both structures. The bimodal and trimodal cells were
      also dominated by visual sensitivity. (c) The somatosensory and auditory
      modalities were similarly present in both structures, although less frequently
      than the visual one. (d) No systematic topological organization was found in
      either structure. (e) The visual, somatosensory and auditory receptive fields
      were uniform and covered a fairly large proportion of the personal space. 2.
      Statistical comparison of some physiological properties of cells situated deep in
      the AES with those of cells in the insular cortex revealed differences as
      follows: (a) The insular cortex contained significantly more bi- and trimodal
      cells than the sulcal areas. (b) Cells in the insular cortex preferred
      significantly lower stimulus velocities and larger stimuli than cells in the
      depths of the AES. These results seem to support the notion of a suprageniculate
      AES/insular thalamo-cortical multisensory entity. Additionally, the physiological
      differences between the sulcal AES cortex and gyral insula are in agreement with
      the morphological differences found earlier in the afferentation of these areas
      (Norita et al., 1986, 1991).

PMID- 8979840
TI  - The development of topographically-aligned maps of visual and auditory space in
      the superior colliculus.
AB  - The role of the superior colliculus in attending and orienting to sensory stimuli
      is facilitated by the presence within this midbrain nucleus of superimposed maps
      of different sensory modalities. We have studied the steps involved in the
      development of topographically-aligned maps of visual and auditory space in the
      ferret superior colliculus. Injections of fluorescent beads into the superficial
      layers showed that the projection from the contralateral retina displays
      topographic order on the day of birth (PO). Recordings made from these layers at
      the time of eye opening, approximately 1 month later, revealed the presence of an
      adult-like map of visual space. In contrast, the auditory space map in the deeper
      layers emerged gradually over a much longer period of postnatal life. In adult
      ferrets in which one eye had been deviated laterally just before eye opening, the
      auditory spatial tuning of single units recorded in the contralateral superior
      colliculus was shifted by a corresponding amount, so that the registration of the
      visual and auditory maps was maintained. Chronic application of the NMDA-receptor
      antagonist MK801 disrupted the normal development of the auditory space map, but
      had no effect on the visual map in either juvenile or adult animals, or on the
      auditory map once it had matured. These findings indicate that visual cues may
      play an instructive role, possibly via a Hebbian mechanism of synaptic
      plasticity, in the development of appropriately tuned auditory responses, thereby
      ensuring that the neural representations of both modalities share the same
      coordinates. Changes observed in the auditory representation following partial
      lesions of the superficial layers at PO suggest that these layers may provide the
      source of the visual signals responsible for experience-induced plasticity in
      auditory spatial tuning.

PMID- 8979841
TI  - What do developmental mapping rules optimize?
AB  - Convergence ratios between pre- and postsynaptic cells in the visual system vary
      widely between cell classes, areas of the visual field, between individuals and
      between species. Proper stabilization of the convergence and divergence of single
      visual neurons is critical for visual integration generally, and for specific
      functions such as those of rod and cone pathways, or the center and peripheral
      regions of the visual field. In early development, retinal ganglion cells, target
      cells and all their processes are produced in excess and stabilize at certain
      mature values. The intent of the investigations described here is to determine
      what features of cell connectivity are stabilized over normal variability by
      these developmental processes and how such stabilization is accomplished, using
      the developing mammalian retinotectal system as an example. Orderly compression
      of the retinotopic map into a half tectum was induced by a partial tectal
      ablation at birth in hamsters, increasing the ratio of retinal ganglion cells to
      superior colliculus target cells. The convergence problem is solved in this case
      by undersampling the spatial array with respect to normal, preserving local
      spatial resolution, but potentially reducing sensitivity or introducing aliasing
      artifacts. Receptive field sizes of single neurons are indistinguishable from
      normal, and reduction of branching of presynaptic axon arbors is the mechanism of
      the remapping. Behaviorally, though the entire visual field is still represented
      in the remaining colliculus, the solution has a cost in decreased probability and
      increased latency to orient to visual stimuli, particularly in the peripheral
      visual field. The generality of this solution for retinal and other central
      convergence regulation problems is evaluated.

PMID- 8979842
TI  - The effect of damage of the brachium of the superior colliculus in neonatal and
      adult hamsters and the use of peripheral nerve to restore retinocollicular
      projections.
AB  - Using horseradish peroxidase (HRP) tracing technique, we were able to confirm the
      critical age in hamsters as reported previously (SO et al., 1981). Thus,
      following transection of the retinal fibers at the brachium of the superior
      colliculus (BSC) on postnatal-day 4 (P4) or later, no retinocollicular
      projections were observed in the adult stage. However, the retinal fibers were
      observed to reinnervate the superior colliculus (SC) if the BSC was cut on P3 or
      earlier. Physiological recording showed a close to normal retinocollicular map
      following a BSC damage on P0. Although retinal fibers did not reinnervate the SC
      following a BSC cut on or after P4, they could be observed to grow along a
      membrane over the damaged site. Bridging the site of BSC damage in adult hamsters
      using a segment of peripheral nerve (PN), retinal fibers labelled with WGA-HRP
      were observed to reinnervate the SC along the PN graft and visual evoked
      responses could be recorded in the SC showing the PN graft is effective in
      restoring damaged central visual pathways in adult mammals.

PMID- 8979843
TI  - A proposed reorganization of the cortical input-output system.
AB  - This paper proposes a new concept for interpretation of the cerebral cortex. In
      this schema, the cortex is an 'imaging system' which plays an integral part in
      the 'functional circuit' of the living body. This functional circuit is made up
      of five components: the 'imaging system' of the cortex, the 'image forming
      system' of the basal ganglia, thalamus and cerebellum, the 'image-acting system'
      of the brainstem and spinal cord, the 'sensory system' of the sense organs and
      the 'external words.' An image constructed in the cortex yields a purposeful
      movement by way of its outputs through the image-acting system. The image to
      drive the purposeful movement is formed and accumulated in the cortex by trial
      and error under the control of the image-forming system. In the proposed
      organization outlined here, the cortex can be divided into two components, both
      of which have their own input and output for forming and realizing the image. One
      is comprised of specific areas for analyzing proper sensations from the sense
      organs through a specific area of the thalamus (e.g., retinal to lateral
      geniculate to primary visual cortex). The other system is composed of non
      specific areas analyzing more diffuse input from various sensory organs through
      non-specific areas of the thalamus. These two systems work in concert to form
      fundamental and detailed images for purposeful movements through tight
      intercortical connections. Whereas the outputs from non-specific areas yield
      common behaviors regardless of sensory modality, outputs from the specific areas
      controls movements related to a specific sensation. Thus, it is proposed that
      these two systems work cooperatively: the former constructs the image and causes
      the initial movements, and the latter controls the movements to realize the image
      from the changing information of transient conditions. This model differs from
      other models of cortical organization which segregate cortex on the basis of
      sensory-related input regions and motor-related output regions. Existing data is
      consistent with the proposed organizational scheme. Although it may be difficult
      to prove specific aspects of this new model. I believe that the hypotheses
      contained within it will serve as an important foundation for driving future
      research.

PMID- 8979844
TI  - Neural bases of residual vision in hemicorticectomized monkeys.
AB  - In this series of studies, we have attempted to characterize anatomically the
      organization of the retinofugal pathways in monkeys that underwent the surgical
      removal in infancy of the entire left cerebral hemisphere. Hemidecordication in
      baby monkeys produced a transneuronal retrograde degeneration of the retinal
      ganglion cells (RGCs) that affected mainly the foveal rim. Although the density
      of RGCs in this region was drastically diminished, the soma sizes of the
      surviving cells remained normal. The lateral geniculate nucleus (dLGN)
      ipsilateral to the removed cortex was dramatically reduced in size although it
      still showed normal layering. There was a marked reduction in the number of
      neurons in both the parvocellular and magnocellular layers and a heavy gliosis.
      By contrast, the superior colliculus ipsilateral to the lesion was remarkably
      well preserved: although slightly reduced in volume, it showed little gliosis and
      a metabolic activity, as revealed by cytochrome oxidase histochemistry, similar
      to the superior colliculus contralateral to the lesion. Behavioral perimetry
      indicated a partial sparing of vision up to 45 degrees in the 'blind' hemifield.
      We argue that the preservation of the retino-tectal pathway mediates most of the
      residual visual functions found in the 'blind field' of hemispherectomized human
      subjects.

PMID- 8979845
TI  - Extrageniculostriate vision in humans: investigations with hemispherectomy
      patients.
AB  - Residual vision was assessed in the blind hemifield of one hemispherectomized and
      one partially hemispherectomized patient, using an interval two alternative
      forced choice detection task. Fixation instabilities were controlled by retinal
      stabilization. In both patients, residual vision was found in the hemianopic
      field close to the vertical meridian. This residual vision is largely confined to
      a band not wider the 3 degrees, but there is a local region in each patient where
      it extends more than 3 degrees from the meridian. However, more than 6 degrees
      from the vertical meridian we found no indication of residual function in either
      patient. Within the band of spared vision, subjects are aware of stimuli and can
      perform simple shape discriminations. Visual acuity profiles argue against an
      explanation based on eccentric fixation. Explanations based on the retino-tectal
      pathway or on retinal naso-temporal overlap are possible.

PMID- 8979846
TI  - Visual inputs to cerebellar ventral paraflocculus during ocular following
      responses.
AB  - The activity of cerebellar Purkinje cells was recorded in the ventral
      paraflocculus (VPFL) of alert monkeys during ocular following responses induced
      by brief movements of the visual scene. The mossy fiber input evoked 'simple
      spikes' which increased their activity during either ipsiversive or downward
      motion of the visual scene. On the other hand, the 'complex-spikes' evoked by the
      climbing fiber input increased their activity during either contraversive or
      upward movement. To further define the sources of the visual input to the VPFL,
      we recorded single units in the dorsolateral pontine nucleus (DLPN), which is
      known to project to the VPFL as mossy fibers, and in the pretectal nucleus of the
      optic tract (NOT), which is known to project to the inferior olive whose neurons
      project to the cerebellum as climbing fibers. In both areas, most neurons were
      directionally selective, and responded to the moving visual scene with very short
      latencies (approximately 40-60 ms). These results suggest that both DLPN and NOT
      neurons deliver information concerning movements of the visual scene to the VPFL
      through different pathways.

PMID- 8979847
TI  - Context dependent discharge characteristics of saccade-related Purkinje cells in
      the cerebellar hemispheres of the monkey.
AB  - In the previous paper (Mano et al, 1991), we reported the discharge patterns of
      saccade-related Purkinje cells during visually guided saccade task, which were
      recorded from posterior cerebellar hemisphere, the Crus IIa. In the present
      study, we analysed these P-cell's simple spike activity during the spontaneous
      saccade in inter-trial intervals (ITI) of visually guided saccade task, comparing
      with the activity during the visually guided saccade. We found that the
      modulation of simple spike discharges during spontaneous saccade was weaker than
      the modulation during the visually triggered saccade. We recorded single unit
      discharges of Purkinje cells from cerebellar posterior hemisphere (Crus IIa) in
      awake Japanese monkeys (Macaca fuscata), trained to perform simple reaction time
      saccade task gazing at a small light rear-projected on to a tangent screen 54 cm
      in front of the monkey. Horizontal and vertical eye positions were measured by a
      corneal search coil method. Comparison of simple spike activity associated with
      spontaneous saccade during ITI to the activity during visually triggered saccade
      clarified that the discharge patterns of simple spikes are basically the same
      during both types of the saccades, but the amount of the phasic modulation
      (increase of decrease of discharge rate) were larger for all directions (up,
      down, left and right) during visually guided saccade than that during spontaneous
      saccade in all saccade-related Purkinje cells so far examined in two monkeys. The
      modulation, however, cannot be assumed to have been induced by the visual
      stimulus per se. Because, the maximum increase of simple spike discharge rate
      aligned at saccade onset is larger than that aligned at target jump. And, the
      half width of the change was wider when aligned at target light jump than when
      aligned at the onset of saccades, in all the four directions, indicating the
      changes of the firing rate were more time-locked to the onset of saccadic eye
      movements than to the triggering visual stimulus. The present findings suggest
      that the cerebellar hemisphere plays a more important role in the control of
      externally triggered voluntary eye movements than in the control of self
      initiated, self-paced eye movements. We discussed these findings combining with
      previous findings on limb movement-related P-cells (Mano et al, 1980, 1986,
      1989), from view point of the general role of the cerebellar hemisphere in the
      control of voluntary movements.

PMID- 8979848
TI  - Further evidence for the specific involvement of the flocculus in the vertical
      vestibulo-ocular reflex (VOR).
AB  - We examined the simple-spike activity of floccular Purkinje (P) cells during
      sinusoidal pitch rotation and vertical optokinetic stimuli in alert, head-fixed
      cats. The great majority of pitch-responding P cells also responded to
      optokinetic stimuli with increased activity when the directions of the resultant
      eye movements were the same. During rapid modification of the VOR induced by
      visual pattern movement, modulation amplitudes of the cells tested increased
      together with the eye velocity increase. Maximal activation directions of these
      cells studied during vertical rotation in many planes were near the vertical
      canal planes. These results suggest that the activity of the majority of pitch
      responding P cells contains a vertical eye velocity component during vestibular
      or optokinetic stimuli in addition to canal inputs during pitch rotation.

PMID- 8979849
TI  - Recommendations for preventing the spread of vancomycin resistance. Hospital
      Infection Control Practices Advisory Committee.

PMID- 8979850
TI  - Japanese encephalitis acquired in Australia.

PMID- 8979851
TI  - Emerging Infectious Diseases Laboratory Fellowship Program.

PMID- 8979852
TI  - Emerging infectious diseases featured at ICAAC/IDSA meeting.

PMID- 8979853
TI  - BSE meeting at CDC.

PMID- 8979854
TI  - "Sinking Into the Ground": The Development and Consequences of Shame in
      Adolescence
AB  - Although in recent years the developmental antecedents and clinical consequences
      of shame have received increased theoretical and research attention, little is
      yet known about shame's development after early childhood or its role in
      developmental psychopathology. This article reviews the literature on shame and
      on adolescence and suggests that attention to the role of shame in adolescent
      development is warranted for several reasons. Social-cognitive, physical, and
      interpersonal changes associated with adolescence may each be associated with
      normative increases in shame during adolescence. In addition, several lines of
      evidence converge to suggest that shame may be implicated in some of the
      important gender-related shifts in self-esteem and developmental psychopathology
      that occur over the adolescent years.

PMID- 8979855
TI  - Henri Wallon's Theory of Early Child Development: The Role of Emotions
AB  - The present paper gives an account of part of the stage theory of early child
      development of the French theorist Henri Wallon (1879-1962). Unlike his
      contemporary Jean Piaget, Wallon concentrated his efforts upon a description of
      the child's emotional development and the role emotions play in establishing the
      bond between child and caregiver. The description of Wallon's stage theory is
      preceded by biographical information and a presentation of his methodological
      views. It is argued that Wallon's theory is unique in its focus, exerted
      influence upon theorists such as Lev Vygotsky, and is basically compatible with
      modern insights about the nature of child development and the growth of
      intersubjectivity.

PMID- 8979856
TI  - Language and Operations in Children's Class Inclusion Reasoning: The Operational
      Semantic Theory of Reasoning
AB  - In this article we critique two prominent theories of reasoning-mental logic and
      mental models-and argue that reasoning does not consist of either applying
      logical rules or constructing mental models. Instead, we propose an operational
      semantic theory of reasoning, according to which reasoning is based on children's
      operational understanding of key terms in a given problem. We then go on to
      consider an important recent developmental theory of reasoning, fuzzy-trace
      theory. In order to illustrate the view of reasoning proposed here we report a
      study of class inclusion. Dramatic differences in class inclusion performance
      were found as the result of linguistic context; performance was significantly
      higher when an explicit request for a subclass comparison preceded the class
      inclusion question as compared to a standard condition when the class inclusion
      question alone was asked. This was the case, however, only when the prior
      subclass comparison question referred to the same dimensions as the class
      inclusion question and not when irrelevant subclasses were referred to.
      Children's performance was also better when they sorted the materials into the
      supraordinate class as compared to the subclasses, but not when the experimenter
      sorted them for the child. These effects due to the operational and linguistic
      manipulations are discussed in terms of a general operational semantic theory of
      reasoning.

PMID- 8979857
TI  - Developmental Accounts of Intentionality: Toward Integration
AB  - A variety of developmental accounts of intentionality, arising from disparate
      theoretical perspectives, can now be found in the literature. This paper argues
      that this diversity is undermining the ability of developmental psychologists to
      construct a coherent developmental account of the capacity and that it would be
      more productive to pursue an integrated approach. To this end, the dominant
      theoretical positions on the development of intentionality are reviewed and
      evaluated: intentionality as goal-directedness, a result of parental scaffolding,
      an innate capacity for intersubjectivity, and behavioral object-directedness.
      Particular attention is given to comparing three key features of each position:
      the definition of intentionality adopted, the types of behaviors considered to be
      evidence of intentionality, and the proposed developmental sequence. The
      possibility of constructing an integrated approach based on these components is
      explored.

PMID- 8979867
TI  - Individual Differences in Interest and Narrative Writing
AB  - Two hundred twenty-four undergraduate students wrote about one-half of an inning
      of a baseball game and about one-half of a soccer game, counterbalanced, for 20
      min each. Students then completed two six-item interest inventories-one each on
      the topics of baseball and soccer-and tests of baseball knowledge and soccer
      knowledge. Hierarchical regression analyses revealed that individual interest in
      baseball was significantly related to the proportions of game actions and
      irrelevant-nongame actions, controlling for gender, discourse knowledge, and
      topic knowledge. Topic knowledge was significantly related to thematic maturity,
      controlling for gender and discourse knowledge. Students wrote more topic
      relevant information on the baseball story-a relatively high-interest topic-than
      on the soccer story, a relatively low-interest topic. Implications for the Flower
      and Hayes (1981) writing model and for assigning students writing topics are
      discussed.

PMID- 8979868
TI  - Self-Efficacy Beliefs and Mathematical Problem-Solving of Gifted Students
AB  - Path analysis was used to test the predictive and mediational role that self
      efficacy beliefs play in the mathematical problem-solving of middle school gifted
      students (n = 66) mainstreamed with regular education students (n = 232) in
      algebra classes. Self-efficacy of gifted students made an independent
      contribution to the prediction of problem-solving in a model that controlled for
      the effects of math anxiety, cognitive ability, mathematics GPA, self-efficacy
      for self-regulated learning, and sex. Gifted girls surpassed gifted boys in
      performance but did not differ in self-efficacy. Gifted students reported higher
      math self-efficacy and self-efficacy for self-regulated learning as well as lower
      math anxiety than did regular education students. Although most students were
      overconfident about their capabilities, gifted students had more accurate self
      perceptions and gifted girls were biased toward underconfidence. Results support
      the hypothesized role of self-efficacy in A. Bandura's (1986) social cognitive
      theory.

PMID- 8979869
TI  - Disciplinary Differences in Self-Regulated Learning in College Students
AB  - The personal attributes of self-regulated learning are often described in terms
      of knowledge base, adaptive motivational beliefs, and appropriate use of
      cognitive and metacognitive strategies for learning. These attributes are usually
      assumed to apply across all disciplines and contexts, but there has been little
      research that has examined the disciplinary differences in these personal
      attributes of self-regulated learning. The present study examined college
      students' knowledge, motivation, and self-regulatory learning strategies in
      humanities, social science, and natural science college courses. The sample
      included 380 college students from three different institutions. Students were
      given a measure of their course knowledge and a self-report measure of their
      motivational beliefs and use of self-regulatory strategies at the beginning and
      end of the semester. Three levels of achievement were created from final course
      grade and ANOVA's were used to examine the differences in knowledge, motivation,
      and self-regulation by achievement level and discipline. The results suggest that
      the components of knowledge, motivation, and self-regulation do distinguish high
      from low achievers in social and natural science courses, but not in the
      humanities courses. Results are discussed in terms of the generalizability of our
      models of self-regulated learning across disciplines and implications for
      measuring self-regulated learning in different disciplines.

PMID- 8979870
TI  - Causal Attributions and Reading Achievement: Individual Differences in Low-Income
      Families
AB  - In this study the development of causal attributions about reading within low
      income families was examined. Specifically, relations between children's reading
      achievement and their causal attributions were investigated as well as relations
      between the children's attributions about themselves and their parents'
      attributions about them. A total 513 students from Grades 3, 6, and 9, and one
      parent of each student, all from low-income families, participated. Students and
      parents independently rated the importance of seven causal variables (effort,
      intellectual ability, liking for reading, the teacher, help at home, difficulty
      of reading material, and luck) for the students' good and poor reading outcomes.
      The major findings were that (a) at each grade, students' attributions were
      reliably related to their reading achievement on the Gates-MacGinitie reading
      comprehension test, with attributions to ability, liking for reading, and help at
      home especially critical; (b) at each grade, parent attributions were reliably
      associated with student attributions; and (c) as students' grade in school
      increased, they focused more on themselves and less on others as causal
      determinants of their reading performance. The implications of these findings for
      research and education are discussed.

PMID- 8979871
TI  - Engagement in Academic Work: The Role of Learning Goals, Future Consequences,
      Pleasing Others, and Perceived Ability
AB  - Engagement in academic work was viewed from a multiple goals perspective. Two
      studies were conducted in which high school math students completed an instrument
      measuring five goals students might have for doing academic work (learning goals,
      performance goals, obtaining future consequences, pleasing the teacher, and
      pleasing the family), perceived math ability, self-regulatory activities,
      strategies (deep or shallow) used when studying for math, and the amount of
      effort and persistence expended on the class. Factor analysis indicated that the
      five goals scales and the perceived ability scale represented unique factors. The
      correlations among the variables revealed theoretically consistent
      interrelationships. Multiple regression analyses indicated that various goals
      (e.g., learning goals, obtaining future consequences, and pleasing the teacher),
      perceived ability, and some interactions accounted for significant amounts of
      variance in the task engagement measures (self-regulation, strategy use, effort,
      and persistence) and achievement. Results are discussed in relation to current
      theory and their practical implications.

PMID- 8979872
TI  - Individual Differences in Adapting to Three Different Tasks of Selecting
      Information from Texts
AB  - This study examined individual differences in selecting main points according to
      three types of tasks. In all, 133 students (10th-graders) participated. Each
      student studied three instructional texts, and each text was preceded by one
      instruction. In the linguistic task, the students had to underline the author's
      main points. In the educational task, students had to underline text elements
      considered to be important by a portrayed teacher. And in the interest task,
      interesting text fragments had to be underlined. The students were divided into
      five groups identified by a typical selection pattern. Only 24 students adjusted
      their selection of main points to each of the tasks (the adaptive group). This
      group differed in some study strategies and learning conceptions from the
      nonadaptive groups. In all, this study begins to give more insight into
      individual differences in selecting main points.

PMID- 8979873
TI  - Memory for Relevant and Irrelevant Information: Evidence for Deficient Inhibitory
      Processes in Language/ Learning Disabled Children
AB  - The present study examined whether language/learning disabled children have
      greater difficulty than nondisabled children suppressing information that becomes
      irrelevant during a sentence processing and memory task. During study trials,
      children were asked to predict and remember the terminal nouns for a series of
      sentences that highly constrained a terminal noun. For half of the study trials
      (fillers) the child's prediction was confirmed by presenting the child with the
      expected ending (e.g., "Butterflies fly by flapping their . . . wings."). For the
      remaining study trials (critical trials), however, the sentence ending expected
      by the child was disconfirmed with a low-probability ending (target noun). Thus,
      when presented with the sentence, "We made a sandwich with peanut butter and . .
      . ," the child's prediction ("jelly") was disconfirmed with a different ending
      ("bananas"). Memory for the disconfirmed and target nouns of critical study
      trials were subsequently tested implicitly with a new sentence-completion task.
      In this case, memory for disconfirmed and target nouns that had been associated
      with individual study sentences were measured in terms of priming effects. The
      analysis of priming effects indicated that language/learning disabled children
      experienced greater difficulty than nondisabled children inhibiting the
      activation of irrelevant information (disconfirmed nouns) and sustaining the
      activation of relevant information (target nouns) during a verbal memory task.
      These results were discussed in terms of their implications for some of the
      memory and language difficulties of language/learning disabled children.

PMID- 8979874
TI  - The Effects of Cooperative Learning on Student Achievement and Motivation in a
      High School Geometry Class
AB  - In this study, the effects of a form of cooperative group instruction (Student
      Teams Achievement Divisions) on student motivation and achievement in a high
      school geometry class were examined. Eighty students were randomly assigned to
      either a control group receiving traditional instruction or one of two treatment
      groups receiving cooperative learning instruction. Geometry achievement was
      assessed using scores from the IOWA Test of Basic Skills and teacher-made exams.
      An 83-item questionnaire was used as a pretest, posttest, and post-posttest
      assessment of efficacy, intrinsic valuing, goal orientation, and cognitive
      processing. Students in the cooperative treatment groups exhibited significantly
      greater gains than the control group in geometry achievement, efficacy, intrinsic
      valuing of geometry, learning goal orientation, and reported uses of deep
      processing strategies. The implications for cooperative group structures and
      motivation theory are discussed.

PMID- 8979875
TI  - The Effects of Autonomy on Motivation and Performance in the College Classroom
AB  - The goals of this study were to extend the literature about classroom autonomy in
      several ways. First, since previous research on autonomy has tended to focus on
      younger learners, we examined whether the positive effects of autonomy on
      motivation and performance would be replicated in a college sample. Second, we
      tested to see whether the well-established links between intrinsic motivation and
      autonomy would also be found using motivational constructs that play key roles in
      learning (specifically, task value, self-efficacy, and test anxiety). Third, we
      sought to trace the effect of autonomy on changes in student motivation over the
      course of a semester. Finally, we examined the role of autonomy on course
      performance. We found that experiences of classroom autonomy in the college
      classroom were more closely related to motivational factors than to performance.
      While the immediate experience of autonomy may not be directly facilitative of
      high course grades, autonomy does seem to foster intrinsic goal orientation, task
      value, and self-efficacy, all of which are critical components of "continuing
      motivation." The data presented here lend further support for the benefits of
      fostering autonomy within academic settings.

PMID- 8979876
TI  - Text Learning Using Scientific Diagrams: Implications for Classroom Use
AB  - In two experiments, eighth-graders viewed ecologically valid diagrams and then
      read a text containing multiple feature-to-fact associations or studied the same
      materials in reverse order. Using the Kulhavy and Stock model of text learning
      using organized spatial displays, it was predicted that those students viewing
      the diagram prior to reading the text would recall more facts and features than
      subjects viewing the material in the reverse order. These predictions were well
      supported. In addition, since the materials used in the experiments were created
      from actual classroom materials, these experiments examined whether the model for
      text learning is also valid using this type of materials. In this area the model
      proved to be very effective as well.

PMID- 8979877
TI  - The Development of Measures of Individual Differences in Self-Regulatory Control
      and Their Relationship to Academic Performance
AB  - Two studies are reported describing the development and validation of the
      Strategic Flexibility Questionnaire (SFQ): a self-report instrument aimed at
      eliciting students' beliefs about the need for, and conditional nature of, self
      regulatory control over learning. In Study 1, 281 first-year university education
      students completed a 40-item pilot questionnaire. Factor analysis of responses
      revealed a 21-item instrument indicating three types of control beliefs: adaptive
      executive control, inflexible executive control, and irresolute executive
      control. In Study 2, the predictive validity of these conceptions was tested
      against the academic performance of 105 third-year university education students.
      Results indicated that students reporting adaptive executive control beliefs were
      more successful academically, while those students reporting inflexible or
      irresolute control beliefs were significantly less successful academically.

PMID- 8979932
TI  - Ambivalence and Persuasion: The Processing of Messages about Immigrant Groups
AB  - Previous research has found that ambivalence is an important characteristic of
      attitudes toward minority groups. In the present research, we determined whether
      people who are ambivalent toward a minority group exhibit more systematic
      processing of persuasive messages pertaining to the group than do people who are
      not ambivalent toward the group. To test this hypothesis, we measured 113
      participants' ambivalence toward Oriental people. After a delay, the participants
      were presented with a persuasive message that contained either strong or weak
      arguments in favor of immigration from Hong Kong. We examined the effects of the
      persuasive message on agreement with immigration from Hong Kong, attitudes toward
      residents of Hong Kong, and immigration-relevant thoughts. In accordance with our
      hypothesis that ambivalence leads to systematic processing, we predicted first
      that the strong message would cause ambivalent participants to be more favorable
      toward residents of Hong Kong and toward their immigration from Hong Kong than
      would the weak message; this tendency was expected to be weaker among
      nonambivalent participants. Second, we predicted that the effect of message
      strength on ambivalent participants' agreement with immigration from Hong Kong
      would be mediated by their immigration-relevant thoughts. Results indicated
      support for both predictions.

PMID- 8979933
TI  - Social Corroboration and Opinion Extremity
AB  - Four studies found that social corroboration of one's (pro/con) attitudinal
      position leads to increases in attitude extremity. Study 1 focused on attraction
      ratings made by college women. This study demonstrated both increases in opinion
      extremity following corroboration and decreases in opinion extremity following
      contradiction. Study 2 focused on dental chair comfort ratings made by dental
      patients and found greater opinion extremity following corroboration from either
      fellow patients or the dentist. Study 3 reported greater charity donation amounts
      as well as heightened opinion confidence following corroboration. Study 4
      replicated Study 1 varying duration of stimulus exposure and found that, as
      predicted, confidence scores were affected more by the
      corroboration/contradiction manipulation when initial exposures were brief.
      Unexpectedly, however, the affect of corroboration on attraction ratings, was not
      moderated by initial exposure time. Rather, across both long and short exposure
      times, attraction scores were most extreme following corroboration and least
      extreme following contradiction. Path analyses in Study 4 supported the view that
      this association between corroboration and extremity was mediated by confidence.
      This research indicates that the relationship between corroboration and opinion
      extremity appears to be respectably robust across populations and target
      variables, and is not specific to sensitive within subject designs. Moreover,
      Study 3 indicates that social corroboration is capable of increasing the
      extremity of behavior having real consequences for participants. The data are
      discussed in terms of possible moderator variables, as well as theories of group
      polarization and opinion extremity.

PMID- 8979934
TI  - The Effects of Direct and Indirect Experience on Affective and Cognitive
      Responses and the Attitude-Behavior Relation
AB  - The present paper investigated the effects of direct and indirect experience on
      the production of affective and cognitive responses. In Study 1, we hypothesized
      that direct experience with an attitude object would tend to produce more
      affective reactions than indirect experience with the object and, alternatively,
      that indirect experience would produce more cognitive reactions than indirect
      experience with the object. To test this, participants were given either a direct
      or an indirect experience with a set of puzzles and then required to indicate
      their reactions to the puzzles. As predicted, direct experience produced more
      affective reactions and indirect experience produced more cognitive reactions. In
      Study 2, we hypothesized that attitudes produced after direct experience would
      predict consummatory behavior better than instrumental behavior and that
      attitudes produced after indirect experience would do the opposite. Again the
      results supported the hypothesis. In Study 3, we hypothesized that attitude
      accessibility mediates the relationships found in Study 2. That is, in a
      consummatory situation attitudes formed through direct experience are more
      assessable that attitudes formed through indirect experience. The results
      supported the hypothesis.

PMID- 8979935
TI  - Cognitive Processing and the Functional Matching Effect in Persuasion: The
      Mediating Role of Subjective Perceptions of Message Quality
AB  - In two experiments, we examined the hypothesis that subjective perceptions of
      message quality mediate the functional matching effect in persuasion. In
      Experiment 1, participants whose attitudes and behaviors serve primarily a value
      expressive function (i.e., low self-monitors) or a social-adjustive function
      (i.e., high self-monitors) were exposed to persuasive messages that contained
      value-expressive, social-adjustive, or both types of arguments in favor of
      voting. Functionally-relevant messages (i.e., the social-adjustive message for
      high self-monitors and the value-expressive message for low self-monitors)
      produced enhanced perceptions of message quality and persuasiveness, more
      positive attitudes, and more message-related behavior than functionally
      nonrelevant messages. Functionally mixed messages were generally more effective
      than messages containing only functionally nonrelevant arguments, but less
      effective than messages containing only functionally relevant arguments. Path
      analyses indicated that the influence of functional relevance on attitudes and
      behavior was significantly mediated by subjective perceptions of the quality of
      the message. In Experiment 2, we exposed participants to a functionally relevant
      or nonrelevant voting appeal five days before a presidential election. Results
      replicated those of Experiment 1; functionally relevant messages produced more
      favorable attitudes, and this effect was mediated by enhanced perceptions of
      message quality. Finally, postmessage attitudes exerted a significant influence
      on whether participants voted in the election, and this effect was mediated by
      voting intentions. Discussion focuses on the subjective nature of message
      evaluation and on the cognitive processes underlying the functional matching
      effect in persuasion.

PMID- 8979936
TI  - Conditioned Inhibition Produced by Extinction of a Conditioned Stimulus
AB  - Four experiments used a conditioned taste aversion procedure to examine the
      potential for CS-alone extinction treatment to produce a conditioned stimulus
      that possesses inhibitory properties. In Experiment 1, saccharin was paired with
      LiCl, and then saccharin was presented alone for several trials to produce
      extensive behavioral extinction. Animals receiving this treatment were retarded
      in reacquiring conditioned responding to saccharin relative to control subjects
      receiving conditioning to the flavor for the first time. In Experiment 2, the
      extinguished saccharin stimulus was shown to decrease conditioned responding to a
      known excitor when the two stimuli were presented in compound as a summation
      test. Experiments 3A and 3B replicated the findings of Experiments 1 and 2 while
      providing evidence that the effects were not due to the differential effects of
      neophobia during testing. These three experiments revealed that an extinguished
      conditioned excitor passes retardation and summation tests for conditioned
      inhibition. Experiment 4 found that extinction of a known excitor was slowed when
      the excitor was extinguished in compound with a previously extinguished
      conditioned stimulus. That is, an extinguished CS provided protection from
      extinction to another CS, a finding also consistent with the view that extinction
      produces conditioned inhibition.

PMID- 8979937
TI  - The Importance of Context in the US Preexposure Effect in CTA: Novel versus
      Latently Inhibited Contextual Stimuli
AB  - Three experiments were conducted to examine the role of novel contextual stimuli
      in producing the unconditioned stimulus (US) preexposure effect. Experiment 1
      demonstrated that novel contextual stimuli produce a significantly stronger US
      preexposure effect than familiar or "latently inhibited" contextual stimuli.
      Moreover, subjects preexposed in the presence of latently inhibited contextual
      cues failed to show a significant US preexposure effect. Experiments 2 and 3
      attempted to provide evidence that the addition of a single novel stimulus to the
      latently inhibited context would result in a significantly stronger US
      preexposure effect than when no such novel cue was present. Experiment 3 was able
      to demonstrate this effect. Results are consistent with the Rescorla-Wagner
      (1972) model of conditioning.

PMID- 8979938
TI  - Complex Visual Learning by Rats
AB  - Rats' learning about visual patterns was studied in a computerized Y-maze where
      wide-angle stimuli were viewed from a distance. Many patterns were available;
      some were spatially complex and others were more homogeneous figures. Experiment
      1 used a discrimination paradigm in which a single S+ could be paired with any
      one of 15 different S-s. Hooded rats learned successively six such discrimination
      problems. Their learning rate improved across the series, and comparison with
      controls suggested that the learning-set did not merely reflect simple
      habituation. Experiments 2 and 3 employed Dark Agouti rats, again learning many
      discrimination problems. Each problem comprised a constant stimulus which was
      paired with stimuli which varied in trial-unique fashion. The version in which
      the constant stimulus was nonrewarded (S-) and the varying stimuli rewarded was
      performed better than the converse, constant S+ and varying nonrewarded,
      reflecting rats' preference for relatively unfamiliar stimuli. In the constant S-
      task, rats showed substantial within-problem learning when three novel problems
      were given per day for 20 trials each. Rats are capable of rapid learning about
      complex visual displays if we engage their natural dispositions to use vision for
      distal stimuli and to approach relatively unfamiliar cues.

PMID- 8979939
TI  - Manipulation of Components of Context: The Context Shift Effect and Forgetting of
      Stimulus Attributes
AB  - Seventy-two Sprague-Dawley rats were used to investigate the multidimensional
      features of the context shift effect and the forgetting of stimulus attributes in
      a Pavlovian differential fear conditioning paradigm. One day after training, a
      change in either conditioning box or room context resulted in substantial
      decrements in performance similar to that induced by a shift of both box and room
      contexts. Two weeks after training, a shift of either box or room context exerted
      no significant detrimental effects on responding. However, a combined shift of
      both box and room contexts still induced a severe performance deficit. These
      results suggest that changes in various components of the stimulus context can
      result in similar retention deficits, that several aspects of stimulus attributes
      are forgotten over a delay, and that changing several aspects of the stimulus
      complex can synergistically impair performance.

PMID- 8979940
TI  - Within-Session Changes in Adjunctive and Instrumental Responding
AB  - Rats pressed levers for food delivered by several fixed interval schedules. A
      drinking spout or running wheel was also available during some conditions, but
      not during others. The rate of lever pressing, drinking and running often changed
      within experimental sessions. The within-session patterns of lever pressing did
      not differ when drinking or running was available and when it was not. The
      correlation between the amount of lever pressing and the amount of drinking or
      running at a particular time in the session was inconsistently positive or
      negative. Finding within-session changes in responding for adjunctive behaviors
      implies that the factors that produce these changes are present for both
      adjunctive and instrumental behavior. Finding inconsistent correlations between
      instrumental responding and adjunctive behaviors questions arousal and
      interference from adjunctive behaviors as explanations for within-session changes
      in instrumental responding.

PMID- 8979941
TI  - The Effect of a Discrete Signal on Context Conditioning: Assessment by Preference
      and Freezing Tests
AB  - Four experiments with rats assessed conditioning to contextual cues after the
      delivery of footshocks that were either signaled by a discrete stimulus or
      unsignaled. Two different tests were used. The first was a context preference
      test in which subjects were allowed to move freely in a brightly lit,
      unconditionally aversive context and the former shock context. The second test
      consisted of scoring freezing behavior while the animals were confined to the
      former conditioning context. During context preference tests, signaled-shock
      animals spent more time in the conditioning context and/or entered that context
      more frequently than did unsignaled-shock subjects. However, freezing tests
      largely failed to detect a difference between groups. These results were
      discussed in terms of possible interactions between the formation of context
      shock, signal-shock, and context-signal associations and their effect on
      performance in each of the two types of tests.

PMID- 8979942
TI  - Signaled Delay of Reinforcement: Effects of Postconditioning Manipulation of
      Context Associative Strength on Instrumental Performance
AB  - Two experiments examined the influence of postconditioning treatments of
      contextual cues on instrumental responding acquired with a signaled delay of
      reinforcement schedule. In Experiment 1, mere exposure to the conditioning
      context after instrumental training resulted in an attenuated response rate
      during an extinction test. In the second experiment, responding was decreased by
      exposure to the contextual cues or sessions in which signaled noncontingent
      reinforcements occurred. The greatest response decrement, however, occurred
      following unsignaled noncontingent food presentations. The results are discussed
      with respect to the different roles of contextual cues on operant responding.

PMID- 8979943
TI  - Visual Reinforcement Signals Interfere with the Effects of Reinforcer Magnitude
      Manipulations
AB  - Three experiments examined the effect of reinforcement magnitude on free-operant
      response rates. In Experiment 1, rats that received four food pellets responded
      faster than rats that received one pellet on a variable ratio 30 schedule.
      However, when the food hopper was illuminated during reinforcer delivery, there
      was no difference between the rates of response produced by the two magnitudes of
      reward. In Experiment 2, there was no difference in response rates emitted by
      rats receiving either one or four pellets of food as reward on a random interval
      (RI) 60-s schedule. In Experiment 3, rats responding on an RI 30-s schedule did
      so at a lower rate with four pellets as reinforcement than with one pellet. This
      effect was abolished by the illumination of the food hopper during reinforcement
      delivery. These results indicate that the influence of magnitude is obscured by
      manipulations which signal the delivery of reinforcement.

PMID- 8979944
TI  - Pairings of a Circular Alley with Apomorphine Produce Conditioned Hyperactivity
AB  - During training trials, some rats were injected with apomorphine as the
      unconditioned stimulus immediately before (Group Forward) or 15 min before (Group
      Backward) exposure to the conditioned stimulus, a circular alley where locomotor
      activity was measured for 30 min. Rats in the control condition (Group Unpaired)
      were not injected until 15 min after their removal from the alley. When the rats
      were later tested in the circular alley without prior administration of the drug,
      both Groups Forward and Backward were more active than Group Unpaired and thus
      showed conditioned hyperactivity. During a final test in which all the rats were
      injected with apomorphine prior to placement in the circular alley, Groups
      Forward and Backward showed greater apomorphine-induced hyperactivity than Group
      Unpaired. Although Group Forward was more active than Group Backward during both
      tests, these differences were not significant. These findings provide further
      evidence for the modulation of drug effects by Pavlovian conditioning.

PMID- 8979945
TI  - Sources of Intertrial Proactive Interference in Rats' Short-Term Memory in a
      Delayed Successive Matching-to-Sample Modality Discrimination
AB  - Rats were trained on a delayed successive matching-to-stimulus modality task
      consisting of onset of chamber lights or a tone for the sample stimulus, S1, and
      a comparison stimulus, S2. Lever pressing to S1 was reinforced as was lever
      pressing to its matching S2 (light-light or tone-tone pairs) but not to its
      mismatching S2 (light-tone, tone-light pairs). The interval between S1 and S2
      within a trial, the retention interval (RI), was varied between 1 and 6 s within
      sessions while the interval between S2 and the next S1, the intertrial interval
      (ITI), was reduced from 24 to 12 s and finally to 6 s over blocks of sessions. In
      Experiment 1, where S1 was kept at 2 s and S2 at 10 s, rats' matching accuracy
      declined over the longer RI, was slightly disrupted as ITIs were reduced to 6 s
      only over 1-s RIs, and was generally poorer to the tone than light S1. In
      Experiment 2, where both stimuli were 10 s increasing RIs caused steeper declines
      in matching accuracy to the tone S1 than light S1 and decreasing ITIs to 6 s
      disrupted rats performance over both RIs. Matching accuracy to the tone but not
      to the light S1 was also poorer when a preceding trial's S2 was a light S2 than
      when it was a tone S2 only during Experiment 2. This intertrial stimulus
      disagreement effect was not influenced by ITI duration. These results suggest
      that intertrial proactive interference in delayed matching tasks consists of two
      separate and independent processes in rats similar to those found in pigeons
      (Edhouse & White, 1988).

PMID- 8979946
TI  - Photodegradation of Polychlorinated Dibenzo-p-dioxins in Liquid Samples by Near
      UV Light Irradiation
AB  - Photodegradation of 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD) in hexane
      solution was studied under controlled near-UV light exposure in the spectral
      region from 325 to 269 nm. GC-MS was used to detect the amount of unreacted
      dioxin and to characterize the relevant degradation products. Irradiation
      experiments carried out at a constant light energy (700 mJ) showed that the
      percentage of 1,2,3,4-TCDD left in the solution after irradiation changed from
      about 55 to 75%, with a minimum of 55% at 310 nm. Further irradiation experiments
      carried out at two wavelengths, namely 310 and 269 nm, and light energy ranging
      from 0 to 4000 mJ, showed that the photodegradation reaction of the TCDD always
      followed a pseudo-first-order kinetic, with a rate constant of 8 x 10(-4) and 5 x
      10(-4) mJ-1, respectively. These experiments also showed that trichloro- and
      dichloro-dibenzo-p-dioxins were produced with less than 15% of the initial
      quantity of TCDD, leading to the conclusion that the dechlorination process is a
      minor photolysis pathway.

PMID- 8979947
TI  - Elements in Wastewater for Agricultural Use
AB  - With the increase in the application of wastewaters for agricultural purposes,
      the determination of the concentrations of some elements that can be found in
      such waters and their temporal behavior are of great interest. In this work,
      treated and untreated sewage samples were analyzed to determine the
      concentrations of Al, Ca, Cd, Cr, Cu, Fe, K, Mg, Na, Ni, Pb, and Zn. Ca, Mg, and
      Na concentrations were determined to estimate the sodium adsorbed ratio index.
      Total residue and setteable solids volume in every samples were also determined.
      With a view to understanding the effects of rainwater on such parameters and on
      treatment plant process efficiency, rain data for the period of observations were
      also collected. Analyses were conducted by atomic absorption spectrophotometry. A
      Perkin-Elmer Model 460 with a nebulizer-flame system and a Perkin-Elmer Model
      5000 with an HGA graphite furnace were used to perform analyses. Principal
      components analysis was performed to simplify the description of the above 13
      parameters and gain a better understanding of their interrelationships.
      Preliminary results showed that rainwater's impact on the concentrations of the
      investigated elements cannot be considered as simple dilution. Each parameter
      follows its own evolution; there is no correlation between treated and untreated
      sewage.

PMID- 8979948
TI  - Determination of Mercury by Inductively Coupled Plasma-Mass Spectrometry
AB  - To control the amount of mercury polluting our environment, mercury has to be
      monitored in all areas of modern life. This requires fast and easy-to-use methods
      that permit the determination of mercury at levels of micrograms per liter. Up to
      now mercury ultratrace determination has required preconcentration or
      amalgamation in order to improve detection limits. This decreases accuracy of
      determination, introducing a longer manipulation of the sample. Inductively
      coupled plasma-mass spectrometry (ICP-MS) allows a direct determination of
      ultratrace mercury, due to the choice of interference free isotopes by the mass
      spectrometer detector. In fact, the detection limit for mercury by ICP-MS is
      0.001 ppb. In the present work results of Hg determinations in different matrices
      by ICP-MS are reported. ICP-MS technique results are better than those of FIMS
      100. This technique is applicable to different solid (minerals and atmospheric
      particulate) and liquid matrices with elimination of interferences. For solid
      matrices methods of attack and dissolution are reported.

PMID- 8979950
TI  - Investigation of Hungarian Moss Species as Toxic Trace Element-Accumulating
      Plants

PMID- 8979949
TI  - Evaluation of the Lead Content in Water for Human Consumption

PMID- 8979951
TI  - Decomposition Products of s-Triazine Herbicides by Electron-Transfer in Acidic
      Aqueous Media
AB  - The reduction of atrazine and terbutylazine was preceded by protonation
      equilibrium. Three protonation sites of the s-triazine molecule determined the
      structure of the final reduction product. Protonation was investigated by the
      change of UV-Vis spectra. Two slightly different pKs corresponding to protonation
      on N5 and N1 heteroatoms were evaluated. The principal reduction pathway involved
      the cleavage of a chlorine atom. A small quantity of desethylatrazine was
      detected in the most acidic media.

PMID- 8979952
TI  - Direct Spectrochemical Analysis of Solids: A Method for Characterization of
      Sediments
AB  - Techniques for the direct analysis of powdered samples provide an advantageous
      alternative to methods using wet digestion in sample preparation. The direct
      spectrochemical methods based on electrothermal vaporization (ETV-ICP-OES, solid
      ETV-AAS, etc.) show a great similarity to the classical method of dc arc
      excitation, used in spectrography. Owing to this, the classical dc arc
      spectrographical method was used in parallel with ETV methods in the direct solid
      sampling analysis of river and basin sediments. The calibration procedure is the
      major difficulty of all techniques applied to direct solid sample analysis
      because of a lack of suitable reference materials. Consequently, it was necessary
      to verify the application of model calibration samples, preferentially using the
      simple dc arc OES system and both spectrographic and spectrometric evaluation.
      The performance parameters of the methods mentioned are compared with those
      published for the ETV-ICP-OES and SS-ETV-AAS methods.

PMID- 8979953
TI  - Polychlorobiphenyls in Antarctica
AB  - The presence and the distribution of polychlorobiphenyls (PCBs) in Antarctic
      environmental components and the effect of the seasonal formation/melting process
      of pack ice on the pollution level of seawater were investigated. Seawater,
      marine, and lake sediment and soil samples were collected in a large area of the
      Ross Sea and Victoria Land during the 1988-1989, 1989-1990, 1990-1991, and 1991
      1992 Italian expeditions. The results obtained highlighted a low and quite
      homogeneous PCB contamination of the studied area. Surface seawater samples from
      Gerlache Inlet and Wood Bay showed a typical PCB concentration of 130 pg/liter,
      and an increase after pack ice melting of about 30-40%. Marine sediment, lake
      sediment, and soil samples showed normalized mean PCB contents of 150, 240, and
      130 (pg/g)/(m2/cm3), respectively.

PMID- 8979954
TI  - Optimization of Flow Injection On-Line Microcolumn Preconcentration of Ultratrace
      Elements in Environmental Samples prior to Their Spectrochemical Determination
AB  - The preconcentration of some elements such as Cd, Co, Ni, and V(IV) was modeled
      in the presence of complexing agents such as citrate and oxalate at high Ca, Mg,
      and sulfate concentrations on iminodiacetic acid/ethyl cellulose (IDAEC), a
      chelating cellulose. The effect of the species present in the solution was
      studied after construction of the species distribution curves using critical,
      estimated, and measured stability constants. The stability constants of the IDAEC
      chelates were determined potentiometrically. The constants were calculated or
      estimated using computer programs. The diagrams calculated in homogeneous media
      were used for optimization of the flow injection on-line preconcentration for
      analysis of ultratrace metals in the highly mineralized water "Hunyadi."

PMID- 8979955
TI  - Determination of Cd, Co, Cu, Mn, Ni, Pb, and Zn by Inductively Coupled Plasma
      Mass Spectroscopy or Flame Atomic Absorption Spectrometry after On-line
      Preconcentration and Solvent Extraction by Flow Injection System
AB  - The concentrations of Cd, Co, Cu, Mn, Ni, Pb, and Zn in natural and sea waters
      are too low to be directly determined with by flame atomic absorption
      spectrometry (FAAS) or graphite furnace atomic absorption spectrometry (GFAAS).
      Specific sample preparations are requested that make possible the determination
      of these analytes by preconcentration or extraction. These techniques are
      affected by severe problems of sample contamination. In this work Cd, Co, Cu, Mn,
      Ni, Pb, and Zn were determined by inductively coupled plasma mass spectroscopy
      (ICP-MS) or by atomic absorption spectrometry, in fresh and seawater samples,
      after on-line preconcentration and following solvent elution with a flow
      injection system. Bonded silica with octadecyl functional group C18, packed in a
      microcolumn of 100-&mu;l capacity, was used to collect diethyldithiocarbamate
      complexes of the heavy metals in aqueous solutions. The metals are complexed with
      a chelating agent, adsorbed on the C18 column, and eluted with methanol directly
      in the flow injection system. The methanolic stream can be addressed to FAAS for
      direct determination of Cu, Ni, and Zn, or collected in a vial for successive
      analysis by GFAAS. The eluted samples can be also dried in a vacuum container and
      restored to a little volume with concentrated HNO3 and Milli-Q water for analysis
      by ICP-MS or GFAAS.

PMID- 8979956
TI  - The Role of Chirocephalus diaphanus in the Early Recognition of Environmental
      Pollution by Trace Elements
AB  - A study was undertaken to evaluate whether the fairy shrimp Chirocephalus
      diaphanus (Crustacea: Anostraca) could be considered as a species capable of
      biomonitoring environmental contamination by accumulating trace elements. This
      preliminary investigation aimed at assessing the levels of As, Cd, Cu, Hg, Pb,
      Se, and Zn in natural waters as well as in adults and cysts of fairy shrimps
      sampled from five different sites in central Italy. Trace elements were
      determined by inductively coupled plasma (ICP)-based spectrometry. In particular,
      ICP-mass spectrometry (ICP-MS) was resorted to in most cases due to its high
      detection power. Pretreatment of samples (adults and cysts) consisted basically
      in the HNO3-assisted microwave digestion of the material. The highest levels of
      trace elements were found in the anostracan cysts, with concentration ranges
      (MUg/g) of 0.464-3.11 for As, up to 0.820 for Cd, 2.62-13.0 for Cu, 0.011-0.213
      for Hg, 0.966-8.46 for Pb, 0.295-2.45 for Se, and 16.4-50.4 for Zn. On the other
      hand, the lowest concentrations were found in natural waters, with values close
      to the ICP-MS detection power for some elements. These data are probative of a
      bioconcentration process, the extent of which is proportional to the
      environmental level of each element. This may turn out to be useful in planning
      biological monitoring and assessing ecotoxicological consequences which might
      ensue from the diffusion of the exploitation of such organisms in aquaculture.

PMID- 8979957
TI  - Stability of Mercury Dilute Aqueous Solutions: An Open Issue
AB  - In the framework of the activities of the European Commission Reference
      Laboratory (CRL) for residues at the Istituto Superiore di Sanita a number of
      analytical quality control trials on determination of trace analytes are being
      carried out. As regards trace elements it soon became apparent that the stability
      of Hg dilute aqueous solutions is rather unsatisfactory. An investigation was
      thus undertaken to ascertain the conditions under which the concentration of this
      metal does not appreciably change. Mercury solutions were prepared in high purity
      deionized water in the concentration range 1-10 ng g-1 and the effect of various
      amounts of HNO3 and K2Cr2O7 (alone or in combination) was elucidated by measuring
      the variations with time in the actual concentration of Hg. Determinations were
      performed by both inductively coupled plasma atomic emission spectrometry and
      inductively coupled plasma mass spectrometry. Results show that solutions added
      with 5% (w/w) HNO3 and 0.01% (w/w) K2Cr2O7 do not undergo any significant
      alteration in the nominal content of the analyte for at least 1 month. Similar
      conclusions are reached in the case of solutions enriched in CaCO3, NaCl, NaNO3,
      KH2PO4, KNO3, and Mg(NO3)2.6H2O to mimic acid digests of meat samples. The
      improvement ensuing from the adoption of this approach on the performance of the
      Hg analytical quality control trials is discussed in detail.

PMID- 8979958
TI  - An Attempt to Interpret the Spread of Element Concentration in Antarctic Surface
      Snow: The Same Element in a Given Test Field, Several Elements in Different
      Sampling Fields
AB  - Sampling surface snow on a large test field always leads to a spread of analyte
      concentration data which partly follows a Gaussian distribution and partly a
      rectangular one as can be observed from the analysis of literature data. The
      spread depends on the nonuniformity of the air-snow interface in the field and on
      the extent of reproducibility of all the procedures used from sampling to
      analysis. Consequently a sample relevant to a restricted surface might be poorly
      representative of the surrounding area. Contamination of the sample during the
      gathering and storing steps is assumed to be the main source of nonrandom results
      (outliers). Using various statistical tools we were able to evaluate which part
      of the spread was due to the snow surface nonuniformity in the case of many
      samples collected in the same test field. In the case of samples gathered in
      different geographical areas, the possibility of finding correlations among
      points is greatly enhanced when three or more analytes are considered for each
      sample. When the same correlation is found for some analytes and a variable
      tentatively tested, information can be gained about the source of chemical
      content of snow samples. The use of UV pretreatment of snow samples has been
      proven to cut down the interference of organics on the electrochemical process in
      DPASV, allowing one to obtain accurate and reproducible data.

PMID- 8979959
TI  - Trace Element Determination in Cultivated Mushrooms: An Investigation of
      Manganese, Nickel, and Cadmium Intake in Cultivated Mushrooms Using ICP Atomic
      Emission

PMID- 8979960
TI  - Inductively Coupled Plasma Spectrometry Determination of Marker Elements for
      Childhood Soil Ingestion
AB  - The methodology developed with inductively coupled plasma spectrometry for the
      determination of marker elements (Al, Si, Ti, Zr, Y, Cr, La, Ce, Cr, and Nd) for
      childhood soil ingestion in biological (feces), environmental (dust and soil),
      and food samples are described. The quality assurance-quality control protocol
      for sample preparation, especially for food, diaper, and fecal samples and for
      determination of marker elements are presented.

PMID- 8979961
TI  - Quality Assurance in Mycotoxin Analysis
AB  - Mycotoxin analysis in food and biological fluids is receiving more and more
      concern, in view also of increasing involvement by the European Union regarding
      legislation. Basically all the analytical steps regarding mycotoxin analysis have
      to be performed according to accurate criteria which are strictly connected to
      the quality of results in terms of reliability. The only rationale for reducing
      this difficulty is to apply quality assurance principles. Quality assurance
      principles define, in fact, the rules to be observed for performing this analysis
      with a degree of uncertainty that is as low as may be possible. In particular
      sampling techniques, if carried out improperly, give rise to uncertainty
      concerning the representativeness of samples that is so critical as to induce a
      dramatic source of errors in the final analysis. Therefore it seems appropriate
      to plan training courses for personnel on the various side-effects related to the
      available sampling and subsampling techniques depending on the commodity. Other
      contributions to the overall error derive from improper methodologies used by
      technicians in the pre-treatment step of the samples (incorrect use of glassware,
      standard solutions, etc.), and finally from the operations involved in the whole
      analytical procedure. In addition, the use of reference materials and certified
      reference materials together with the utilization of validated methods of
      analysis will be dealt with as concrete procedures for obtaining the certainty of
      final results of good quality. This aspect takes on a relevant outcome if applied
      to official control activities from authorized bodies acting at a national level.

PMID- 8979962
TI  - Application of Biomarkers to Assessment of Risk to Human Health from Exposure to
      Mycotoxins
AB  - Mycotoxins, the toxic compounds produced by mold secondary metabolism, represent
      a relevant source of danger to humans through alimentary channels. Efforts have
      been made by researchers and by national authorities to assess mycotoxin
      incidence in food, but often results are to be considered approximate or
      inaccurate due to the huge difficulties posed by sampling procedures. More
      recently the evaluation of mycotoxins in biological fluids have been given
      increasing attention since the results may offer valuable indications, although
      general on the overall status of mycotoxin contamination in food and feed. The
      assessment of the degree of exposure to these contaminants in the population or
      in specific groups can also be pursued. Researches on mycotoxins in biological
      fluids greatly contribute to clarify the mechanism of health impairment
      attributable to these toxic compounds and to elucidate the dose-response
      relationship. Despite the considerable efforts devoted to mycotoxin research in
      the past few decades, improvements in methodology has to be achieved mainly in
      sampling procedures and in quality assurance of the laboratories involved in
      mycotoxin analysis, as well as in the selection of appropriate biomarkers.

PMID- 8979963
TI  - Electron Transfer in Donor-Acceptor Molecules of Substituted Naphtoquinones:
      Spectral and Redox Properties of Internal Charge Transfer Complexes
AB  - The investigated compounds were substituted naphtoquinones containing aniline
      moiety separated from the quinoid system by a methylene bridge. The nature of
      substituents on both donor and acceptor parts influenced the degree of formation
      of an internal charge transfer complex. Properties of the internal charge
      transfer interactions were investigated by voltammetry, spectroscopy, and in situ
      spectroelectrochemistry. Quantum chemical interpretation of experiments is given.

PMID- 8979972
TI  - Empirical Recovery of Response Time Decomposition Rules I. Sample-Level
      Decomposition Tests
AB  - E. N. Dzhafarov and R. Schweickert (1995, Journal of Mathematical Psychology, 39,
      285-314) developed a mathematical theory for the decomposability of response time
      (RT) into two component times that are selectively influenced by different
      factors and are either stochastically independent or perfectly positively
      stochastically interdependent (in which case they are increasing functions of a
      common random variable). In this theory, RT is obtained from its component times
      by means of an associative and commutative operation. For any such operation,
      there is a decomposition test, a relationship between observable RT distributions
      that holds if and (under mild constraints) only if the RTs are decomposable by
      means of this operation. In this paper, we construct a sample-level version of
      these decomposition tests that serve to determine whether RTs that are
      represented by finite samples are decomposable by means of a given operation
      (under a given form of stochastic relationship between component times,
      independence or perfect positive interdependence). The decision is based on the
      asymptotic p-values associated with the maximal distance between empirical
      distribution functions computed by combining in a certain way the RT samples
      corresponding to different treatments.

PMID- 8979973
TI  - Empirical Recovery of Response Time Decomposition Rules II. Discriminability of
      Serial and Parallel Architectures
AB  - Among the possible response time (RT) decomposition rules, three are of a
      traditional interest: addition (serial RT architecture), minimum (parallel-OR
      architecture), and maximum (parallel-AND architecture). Given RT samples, one can
      decide which of these three operation is the true decomposition rule by choosing
      the operation producing the smallest Smirnov distance between the RT samples
      combined in a certain way, as described by E. N. Dzhafarov and J. M. Cortese
      (1996, Journal of Mathematical Psychology 40, 185-202). By means of Monte-Carlo
      simulations, we determine at what sample sizes this decision identifies the true
      decomposition rule reliably. The results indicate that for a broad class of RT
      distribution functions the sample sizes required are by an order of magnitude
      larger when the component times are stochastically independent than when they are
      perfectly positively stochastically interdependent. In both cases, however, the
      required sample sizes are realistically achievable in an experiment, provided the
      experimental factors selectively influencing component times are sufficiently
      effective. Addition and maximum are generally more difficult to discriminate than
      addition and minimum, which in turn are more difficult to discriminate than
      maximum and minimum.

PMID- 8979974
TI  - Random Utility Representations of Finite m-ary Relations
AB  - Block and Marschak (1960, in Olkin et al. (Eds.), Contributions to probability
      and statistics (pp. 97-132). Stanford, CA: Stanford Univ. Press) discussed the
      relationship between a probability distribution over the strict linear rankings
      on a finite set C and a family of jointly distributed random variables indexed by
      C. The present paper generalizes the concept of random variable (random utility)
      representations to m-ary relations. It specifies conditions on a finite family of
      random variables that are sufficient to construct a probability distribution on a
      given collection of m-ary relations over the family's index set. Conversely,
      conditions are presented for a probability distribution on a collection of m-ary
      relations over a finite set C to induce (on a given sample space) a family of
      jointly distributed random variables indexed by C. Four random variable
      representations are discussed as illustrations of the general method. These are a
      semiorder model of approval voting, a probabilistic model for betweenness in
      magnitude judgments, a probabilistic model for political ranking data, and a
      probabilistic concatenation describing certainty equivalents for the joint
      receipt of gambles. The main theorems are compared to related results of Heyer
      and Niederee (1989, in E. E. Roskam (Ed.), Mathematical psychology in progress
      (pp. 99-112). Berlin: Springer-Verlag; 1992, Mathematical Social Sciences, 23, 31
      44).

PMID- 8979975
TI  - The Axioms of Quantity and the Theory of Measurement

PMID- 8979976
TI  - Multiple-Event Forced-Choice Tasks in the Theory of Signal Detectability
AB  - Receiver operating characteristic (ROC) analysis is generalized to unidimensional
      forced-choice tasks involving three or more events. It is shown that the
      performance of an observer in a unidimensional identification task with n
      independent events can be represented in n! ROC spaces of dimension n. Each ROC
      space is associated with a unique pairing of the events and decisions. A
      hypersurface can be generated in each ROC space by manipulating the observer's
      decision criteria. Using information theory, a new measure of discriminability
      based on the hypervolumes under the hypersurfaces is defined. This measure,
      denoted D, is nonparametric and independent of the criteria. The value of D is
      shown to increase monotonically with n and to be equal to the channel capacity of
      an observer in an n-interval forced-choice task. Procedures to compute ROC
      hypersurfaces from ratings and from ROC curves are given.

PMID- 8979977
TI  - Pure Rotational Spectra of SO: Rare Isotopomers in the 80-GHz to 1.1-THz Region
AB  - Pure rotational spectra of rare isotopomers of sulfur monoxide, SO, have been
      recorded with the Cologne Terahertz Spectrometer, Germany, and the millimeter-
      and submillimeter-wave spectrometer at Nobeyama, Japan. In total, 176 new
      transitions have been measured in the X3Sigma- electronic ground state, including
      the first laboratory detection of the rare isotopomer 36SO. New lines are also
      reported for 33SO and S17O in their vibrational ground states, and for 33SO and
      S18O in the first excited vibrational state. A simultaneous fit of 451
      transitions has led to an improved set of isotopically invariant parameters for
      rotation and fine structure. Hyperfine structure constants for 33SO and S17O have
      been obtained also from the global fit, including first values for the magnetic
      nuclear spin-rotation interaction. These are compared to other molecules. The
      isotopically invariant parameters allow precise frequency predictions for the
      submillimeter-wave region far beyond 1 THz for all SO isotopomers, of importance
      to astrophysical applica- tions.

PMID- 8979978
TI  - Multiple-Photon Dynamics in Molecules: A New Approach to High Resolution
      Spectroscopy of Highly Excited Vibrational States
AB  - Multi-photon transitions with two simultaneously interacting IR laser fields lead
      to final excited states with frequencies nnu = n1nu1 + n2nu2, with n the total
      number of photons absorbed and (n, n1, n2) = (2, 1, 1), (3, 2, 1), (4, 1, 3),
      etc. The nature of the actual transition is determined by shift measurements,
      where the lasers are frequency-tuned by deltanui in opposite directions keeping
      the sum frequency, nnu, resonant with the molecular transition. This technique
      opens a new spectral range for multi-photon transitions and a unique
      identification of the observed features. For n1 and n2 both positive the
      excitation will lead to a "normal" up-up multi-photon transition. Many three- and
      four-photon transitions in the nu3 vibrational ladder of SF6 could be resolved
      with a resolution of 1 MHz, as well as four new two-photon transitions. As long
      as n1 + n2 >/= 0, one of the two ni may be negative resulting in an, e.g., up
      down excitation pathway with its particular selection rules. The up-down
      excitations are demonstrated both for one- and two-photon transitions using the
      frequency shift technique. The different possible excitation schemes which meet
      the resonance condition for these transitions lead to interference effects and
      local couplings to highly excited states. Changes in resonance frequency for a
      one-photon transition (n = 1), due to these effects, are demonstrated. Evidently,
      the radiative coupling of participating levels to high-lying or quasi-continuum
      states may drastically change for different deltanui leading both to ac Stark
      shift and transition probability variations.

PMID- 8979979
TI  - Line Intensities in the nu6 Band of CH3F at 8.5 MUm
AB  - Infrared absolute line intensities of the nu6 band of CH3F have been measured
      around 8.5 MUm using a diode-laser spectrometer. These line strengths were
      obtained by the equivalent width method and, for 13 lines, by fitting a Rautian
      profile to the measured shape of the lines. From these results, we have deduced
      the vibrational band strength to be S0v = 9.66 +/- 0.13 cm-2 atm-1 at 296 K and
      the first Herman-Wallis factors.

PMID- 8979980
TI  - Line Positions and Intensities of the nu1 + nu2 + 3nu3, nu2 + 4nu3, and 3nu1 +
      2nu2 Bands of Ozone
AB  - Using a Fourier transform spectrometer, we have recorded the spectra of ozone in
      the region of 4600 cm-1, with a resolution of 0.008 cm-1. The strongest
      absorption in this region is due to the nu1 + nu2 + 3nu3 band which is in
      Coriolis interaction with the nu2 + 4nu3 band. We have been able to assign more
      than 1700 transitions for these two bands. To correctly reproduce the calculation
      of energy levels, it has been necessary to introduce the (320) state which
      strongly perturbs the (113) and (014) states through Coriolis- and Fermi-type
      resonances. Seventy transitions of the 3nu1 + 2nu2 band have also been observed.
      The final fit on 926 energy levels with Jmax = 50 and Kmax = 16 gives rms = 3.1 x
      10(-3) cm-1 and provides a satisfactory agreement of calculated and observed
      upper levels for most of the transitions. The following values for band centers
      are derived: nu0(nu1 + nu2 + 3nu3) = 4658.950 cm-1, nu0(3nu1 + 2nu2) = 4643.821
      cm-1, and nu0(nu2 + 4nu3) = 4632.888 cm-1. Line intensities have been measured
      and fitted, leading to the determination of transition moment parameters for the
      two bands nu1 + nu2 + 3nu3 and nu2 + 4nu3. Using these parameters we have
      obtained the following estimations for the integrated band intensities, SV(nu1 +
      nu2 + 3nu3) = 8.84 x 10(-22), SV(nu2 + 4nu3) = 1.70 x 10(-22), and SV(3nu1 +
      2nu2) = 0.49 x 10(-22) cm-1/molecule cm-2 at 296 K, which correspond to a cutoff
      of 10(-26) cm-1/molecule cm-2.

PMID- 8979981
TI  - The Ethylene Hot Band Spectrum near 3000 cm-1
AB  - A new hot band spectrum of ethylene has been recorded from 2970 to 3015 cm-1 at
      low rotational temperatures in a seeded molecular jet, using vibrational energy
      transfer from SF6 to C2H4. An IR-IR double resonance technique has been applied
      to pump the lower states and subsequently probe the hot bands. Two new hot bands,
      nu10 + nu11 - nu10 and nu7 + nu11 - nu7, have been found. The weak hot band
      starting from nu7 has been identified by direct labeling of some rotational
      levels in the nu7 manifold. High resolution FTIR spectra at ambient and at
      elevated temperatures have been recorded, too; it has thus become possible to
      extend the analysis to higher rotational quantum numbers. The previously analyzed
      nu9 + nu10 level has been reinvestigated and a b-type Coriolis interaction with
      the nearby nu7 + nu11 state has been observed. Rotational energy levels of nu7 +
      nu11 and of nu9 + nu10 have been fitted simultaneously, taking into account the
      local perturbations due to five dark states. From the shift of all K not equal 0
      levels to higher frequencies in the nu10 + nu11 state, a global a-type Coriolis
      interaction with nu8 + 2nu12 has been identified.

PMID- 8979982
TI  - Symmetry Analysis of Molecules Consisting of Two Coaxial Rotors Using the
      Extended Permutation-Inversion Groups
AB  - A general method for constructing permutation-inversion groups and their
      extensions to molecules containing two coaxial rotors is presented. Symmetry
      species of the dipole moment, tensor of polarizability, and total angular
      momentum operator are determined. General infrared and Raman selection rules,
      symmetry classifications of rotorsional, rotational, and torsional wavefunctions
      are derived. Theory is illustrated for the H3D+2 complex.

PMID- 8979984
TI  - Laser Spectroscopy of the CCO Radical in the 0.77-MUm Region: Analysis of the
      A(020)kappa3Pi and A3Pii(001) States
AB  - The A(020)kappa3Pi-X3Sigma-(000) and A3Pii(001)-X3Sigma-(000) bands of the CCO
      radical have been investigated by laser spectroscopy with two types of tunable
      laser system. An analysis was made simultaneously for both the bands to establish
      line assignments and determine molecular constants for both the A(020) and A(001)
      states. A coupling constant between these two states was also determined by
      assuming the interaction to be of Fermi type.

PMID- 8979983
TI  - Rotational Spectrum of the Excited Vibrational States of DCOOH and Assignment of
      Optically Pumped Laser Transitions
AB  - The rotational spectrum of DCOOH in the 175-335 GHz region was investigated.
      Analysis of the spectrum made it possible to assign several dozen transitions in
      the nu6, nu8, and nu5 vibrational states and to determine the rotational and
      centrifugal distortion constants. The derived parameters of the nu6 state allowed
      four optically pumped laser transitions to be assigned. In addition, the ground
      state parameters for DCOOH and D13COOH have been improved and for the first time
      those for DC18OOH and DCO18OH have been obtained.

PMID- 8979985
TI  - The First Excited Ca-C-C Bending Vibration Levels in the A2Pi and X2Sigma+ States
      of the CaCCH Radical: The Renner-Teller Effect and K-type Resonance
AB  - The 5(1)0 and 5(1)1 bands of the CaCCH A2Pi-X2Sigma+ transition, corresponding to
      the Ca-C-C bending mode, have been rotationally analyzed through cw dye laser
      excitation and dispersed fluorescence with a CCD array detector. The upper state
      is subject to Renner-Teller and spin-orbit couplings, and strong K-type resonance
      interactions were observed between the nearby 2Delta and 2Sigma vibronic
      components. A model that invokes a full matrix treatment of these interactions
      was employed in a least-squares fit of a total of 708 rotational lines of the two
      bands, recorded with high precision. The fundamental bending frequencies have
      been determined as nu5 = 101.394(1) and 102.940(1) cm-1 for the A2Pi and X2Sigma+
      electronic states, respectively. The Renner-Teller parameter has been determined
      as epsilon5omega5 = 3.528(14) cm-1. The nonadiabatic parameter for the nu5 mode,
      gK = 0.6542(10) cm-1, is in accord with the observation that the 2Delta5/2
      vibronic component lies above the normally highest kappa2Sigma component.

PMID- 8979986
TI  - Spectroscopy of D2O (2,0,1)
AB  - The (2,0,1) <-- (0,0,0) rovibrational transitions of D2O in the near infrared
      region were measured with a resolution of 0.07 cm-1 using photoacoustic laser
      absorption spectroscopy. We report on the assignment of newly observed
      transitions and determine new inertial and centrifugal constants of D2O (2,0,1)
      using the Watson-type A-reduced Hamiltonian for asymmetric tops.

PMID- 8979987
TI  - Determination of the Isotope Shift of the 000 Band of the First Singlet-Singlet
      Electronic Transition of Cl- and Br-Benzene in a Supersonic Beam
AB  - By using resonance-enhanced two-photon ionization in a supersonic beam,
      photoionization spectra of the 0(0)0 band of the first singlet-singlet electronic
      transition of 35Cl-, 37Cl-, 79Br-, and 81Br-C6H5 have been obtained at a
      rotational temperature of 1 K. The ions have been analyzed according to their
      masses in a time-of-flight mass spectrometer. From the spectra of 35Cl- and 37Cl
      C6H5 obtained simultaneously, an isotope shift of 0.14 +/- 0.02 cm-1 has been
      determined. Similarly, from the spectra of 79Br- and 81Br-C6H5 the isotope shift
      resulted to be smaller than 0.02 cm-1. The spectra obtained have been interpreted
      by considering the geometrical structure and symmetry of each molecule, and
      values for the rotational constants and geometrical parameters in the upper and
      lower states have been obtained in agreement with the experimental results.

PMID- 8979988
TI  - The Hot Bands of Methane between 5 and 10 MUm
AB  - Experimental line intensities of 1727 transitions arising from nine hot bands in
      the pentad-dyad system of methane are fitted to first and second order using the
      effective dipole moment expansion in the polyad scheme. The observed bands are
      nu3 - nu2, nu3 - nu4, nu1 - nu2, nu1 - nu4, 2nu4 - nu4, nu2 + nu4 - nu2, nu2 +
      nu4 - nu4, 2nu2 - nu2, and 2nu2 - nu4, and the intensities are obtained from long
      path spectra recorded with the Fourier transform spectrometer located at Kitt
      Peak National Observatory. For the second order model, some of the 27 intensity
      parameters are not linearly independent, and so two methods (extrapolation and
      effective parameters) are proposed to model the intensities of the hot bands. In
      order to obtain stable values for three of these parameters, 1206 dyad (nu4, nu2)
      intensities are refitted simultaneously with the hot band lines. The simultaneous
      fits to first and second order lead to rms values respectively of 21.5% and 5.0%
      for the 1727 hot band lines and 6.5% and 3.0% for the 1206 dyad lines. The band
      intensities of all 10 pentad-dyad hot bands are predicted in units of cm-2 atm-1
      at 296 K to range from 0.931 (for 2nu4 - nu4) to 7.67 x 10(-5) (for 2nu4 - nu2).
      The total intensities are also estimated to first order for two other hot band
      systems (octad-pentad and tetradecad-octad) that give rise to weak transitions
      between 5 and 10 MUm.

PMID- 8979989
TI  - Infrared Transitions of H12C14N and H12C15N between 500 and 10 000 cm-1
AB  - We have measured the Fourier transform spectrum (FTS) of two isotopomers of
      hydrogen cyanide (H12C14N and H12C15N) from 500 to 10 000 cm-1. The infrared data
      have been combined with earlier published microwave and submillimeter-wave
      measurements. From this analysis new vibration-rotation energy levels and
      constants are given, based on the observation of a number of new vibrational
      levels, especially for H12C15N. The Coriolis interaction involving Deltav3 = -1,
      Deltav2 = 3, and Deltal = &plusmn;1 has been observed for a great many levels and
      in some cases the assignments of laser transitions allowed by this interaction
      are more clearly shown. New vibration-rotation constants are given that allow one
      to predict the transition wavenumbers for most of the transitions below 10 000 cm
      1 with accuracies of about 0.5 cm-1 or better. Values are given for the power
      series expansion of the l-type resonance constants and for the centrifugal
      distortion constants, as well as the usual vibrational and rotational constants.

PMID- 8979990
TI  - The Millimeter-Wave Spectrum of 2,3-Dihydrofuran
AB  - The millimeter-wave spectrum of 2,3-dihydrofuran in the ground and five ring
      puckering excited states has been measured in the frequency range 100-250 GHz.
      The ground and first ring-puckering excited states have been fitted to a two
      state Hamiltonian including Coriolis coupling interaction. The determined energy
      difference of 18.684(7) cm-1 between these states and the a and b type coupling
      parameters are consistent with the ring-puckering potential function and the
      previously observed dependence of the centrifugal distortion constants DeltaJK,
      DeltaK, and deltaK. A small ring-puckering dependence of the quartic centrifugal
      distortion constants DeltaJ and deltaJ has been also observed. This dependence is
      well accounted for in terms of the ring-puckering potential function and the
      vibrational dependence of the rotational constants.

PMID- 8979991
TI  - Infrared Laser Spectroscopy of Jet-Cooled C2F6 near 10 &mu;m
AB  - The nu5 (A2u) and nu7 (Eu) C-F stretching fundamentals of hexafluoroethane, C2F6,
      have been recorded in a supersonic jet by diode laser absorption spectroscopy.
      The parallel 5(1)o band is accompanied by five satellite bands, of which three
      have been assigned to hot bands. A fourth satellite band arises from 12CF313CF3.
      Transitions satisfying 0 </= KDeltaK </= 7 of the perpendicular 7(1)o band are
      unperturbed while those having -10 </= KDeltaK </= 7 can be fitted assuming an Rz
      Coriolis interaction with a state lying at nup = 1256 cm-1. A second localized
      perturbation affects lines with KDeltaK >/= 8. The band origins are 1117.10736
      (7) cm-1 (5(1)o) and 1252.96950 (17) cm-1 (7(1)o, 0 </= KDeltaK </= 7), and the
      rotational constant B0 = 0.0615759 (27) cm-1.

PMID- 8979992
TI  - Color Center Laser-Microwave Double Resonance Spectroscopy of the nu1 Vibrational
      State of HCCF
AB  - Rotational transitions of fluoroacetylene in the nu1 (CH stretch) vibrational
      state have been observed by the laser-microwave double resonance technique using
      a color center laser as a radiation source in the 3 &mu;m region. The rotational
      constant and centrifugal distortion constant in the nu1 state were determined to
      be 9684.310(16) MHz and 2.68(62) kHz, respectively, where the uncertainties given
      in parentheses correspond to 2.5 standard deviations.

PMID- 8979993
TI  - N2 Broadening in the 13C16O 2-0 Band around 4167 cm-1
AB  - N2 broadening coefficients have been measured for 65 lines of the 13C16O 2-0 band
      using a Fourier transform spectrometer. These lines are located in the spectral
      range 4011-4252 cm-1. The spectra were recorded with 99% isotopically pure 13CO
      in a White-type cell at a resolution of 0.005 cm-1. Voigt profiles convolved with
      the FTS apparatus function were fitted to the experimental lineshapes using a
      nonlinear least-squares fit technique. From the fits the Lorentzian HWHM was
      determined as function of N2 pressure. Pressure broadening coefficients for m
      between -33 and +34 were obtained with uncertainties of 5.8%. The results are
      compared to earlier published N2 broadening coefficients and our measurements in
      the 2-0 band of 12C16O. To our knowledge this is the first investigation of 13CO
      pressure broadening.

PMID- 8979994
TI  - Fourier Transform Spectroscopy of the Y2Sigma+-X2Pii Transition of CuO
AB  - The Y2Sigma+-X2Pii near-infrared electronic transition of CuO was observed at
      high resolution for the first time. The spectrum was recorded with the Fourier
      transform spectrometer associated with the McMath-Pierce Solar Telescope at Kitt
      Peak. The excited CuO molecules were produced in a low pressure copper hollow
      cathode sputter with a slow flow of oxygen. Constants for the Y2Sigma+ states of
      CuO are: T0 = 7715.47765(54) cm-1, B = 0.4735780(28) cm-1, D = 0.822(12) x 10(-6)
      cm-1, H = 0.46(10) x 10(-10) cm-1, gamma = -0.089587(42) cm-1, gammaD =
      0.1272(79) x 10(-6) cm-1, bF = 0.12347(22) cm-1, and c = 0.0550(74) cm-1.
      Improved X2Pii constants are also presented.

PMID- 8979995
TI  - Microwave and Infrared Spectra, ab Initio Calculation, and Two-Dimensional Model
      of Amino Group Inversion and Ring Puckering in 2,5-Dihydropyrrole
AB  - The microwave spectra of 2,5-dihydropyrrole and 2,5-dihydropyrrole-1-d1 have been
      measured with Stark and Fourier transform spectrometers in the range 10-39 GHz.
      Rotational constants, centrifugal distortion constants, and 14N quadrupole
      coupling constants have been determined from the observed transition frequencies
      for the ground vibrational state. In addition, two satellites of the normal
      species and one satellite of the deuterated species have been identified and
      measured. Splittings of the rotational transitions due to amino group inversion
      tunneling have been observed and analyzed. Infrared transitions of the amino
      group inversion mode have been measured in the range 490-720 cm-1. The effect of
      ring puckering on the inversion motion of the amino group in 2,5-dihydropyrrole
      and 2,5-dihydropyrrole-N-d1 has been investigated by ab initio calculations and
      two-dimensional flexible model calculations from the results of microwave and
      infrared spectroscopy. The observed molecular properties have been reproduced by
      a model which involved adjustable parameters for the potential energy surface and
      the structural relaxation of the CCC valence angles. Additional parameters have
      been transferred from the ab initio calculations. The adjustment of the model to
      the experimental data has yielded an equatorial equilibrium conformation with
      slightly larger CCC valence angle than in the most stable axial conformation.
      Excitation of the first ring puckering state has been found to enhance the
      inversion tunnel splittings.

PMID- 8979996
TI  - Jet Spectroscopy of the D1 22B1-D0 12B1 Transition of the p-Cyanobenzyl Radical
AB  - We have generated the p-cyanobenzyl radical in supersonic free expansion, and
      measured the vibrationally and rotationally resolved laser induced fluorescence
      (LIF) excitation spectra and the LIF dispersed spectra from the single vibronic
      levels (SVL) in the green-blue region. The lowest energy band at 20 738 cm-1 with
      the strongest intensity in the excitation spectrum has been assigned to the 0(0)0
      band of the visible spectrum, on the basis of the vibronic structures in the SVL
      dispersed spectra. Based on the band type of the 0(0)0 band, a-type, determined
      from the rotationally resolved LIF excitation spectrum, we have definitely
      assigned the visible band to the D1 2(2)B1-D0 1(2)B1 electronic transition. We
      have found, on the grounds of the vibrational analysis of the dispersed spectra,
      that the vibronic structure of the 2(2)B1-1(2)B1 electronic transition of the
      benzyl type is characterized by totally symmetric fundamental modes, 1, 8a, and
      9a.

PMID- 8979997
TI  - Transition Moments between 1Deltag, 1Pig, and 1Piu States of the H2 Molecule
AB  - Electronic transition moments are computed for dipole transitions between the C
      and D 1Piu, I and R 1Pig and J and S 1Deltag states of the hydrogen molecule for
      internuclear distances R in [1, 15] bohr. The character of the wavefunctions at
      large internuclear distances is investigated. It is shown that in the D and R
      states the asymptotic configurations are strongly mixed for R </= 15 bohrs. The S
      state has mixed character even at R = 40 bohr.

PMID- 8979998
TI  - The Rotational Spectrum of H2Te
AB  - In the present work, we study the spectrum of the H2Te molecule in the
      submillimeter-wave and far infrared region. An important aim of this
      investigation is the further experimental characterization of the anomalous "four
      fold cluster effect" exhibited by the rotational energy levels in the vibrational
      ground state of H2Te. The spectrum in the region 90-472 GHz was measured with a
      source-modulated millimeter-wave spectrometer and that between 600 and 1600 GHz
      with a far-infrared sideband spectrometer. The far infrared spectrum from 30 to
      360 cm-1 was measured with a Bruker IFS 120 HR interferometer attached to a 3 m
      long cell. We have assigned 224 submillimeter-wave lines and 1695 FIR lines.
      These observed data were supplemented by a large number of ground state
      combination differences derived from rotation-vibration bands of H2Te, and the
      resulting large data set was analyzed by means of a modified Watson Hamiltonian.
      Accurate sets of rotational and centrifugal distortion constants for all eight
      tellurium isotopomers were obtained.

PMID- 8979999
TI  - Fourier Transform Infrared Emission Spectroscopy of the b1Pi-a1Sigma+ System of
      BN
AB  - The emission spectrum of BN has been investigated in the 1800-9000 cm-1 region
      using a Fourier transform spectrometer. BN was formed in a microwave discharge of
      He with a trace of BCl3 and N2. The bands observed in the 3000-7800 cm-1 interval
      have been assigned as the b1Pi-a1Sigma+ transition, with the 0-0 band at
      3513.99040(43) cm-1. This transition is analogous to the A1Piu-X1Sigma+g
      (Phillips) system of the isoelectronic C2 molecule. The rotational analysis of
      the 0-0, 1-1, 1-0, 2-1, 3-2, 2-0, 3-1, 4-2, and 4-1 bands has been obtained and
      the molecular constants for the b1Pi and a1Sigma+ states have been determined. A
      local perturbation has been observed in the v = 1 vibrational level of the b1Pi
      state near J = 18 caused by the interaction with the v = 3 vibrational level of
      the a1Sigma+ state. The principal equilibrium constants for the a1Sigma+ state
      are: omegae = 1705.4032(11) cm-1, omegaexe = 10.55338(52) cm-1, Be =
      1.683771(10), alphae = 0.013857(16) cm-1, and re = 1.2745081(37) A. Although the
      b1Pi-a1Sigma+ transition has recently been seen in emission from boron nitride
      trapped in solid neon matrices [J. Chem. Phys. 104, 3143-3146 (1996)], our work
      represents the first observation of this transition of BN in the gas phase.

PMID- 8980000
TI  - The High-Resolution Fourier Transform Spectrum of Dideuterated Methane CH2D2 in
      the Region between 1900 and 2400 cm-1
AB  - The infrared spectrum of doubly deuterated methane CH2D2 has been recorded in the
      region from 1900 to 2400 cm-1 at almost Doppler-limited resolution by using two
      high-resolution Fourier transform spectrometers. The vibrational bands observed
      include 2nu4, nu4 + nu7, 2nu7, nu2, nu8, nu4 + nu9, and nu7 + nu9, which were
      analyzed by taking into account Coriolis and Fermi interactions among them and
      also those with nu4 + nu5, nu3 + nu7, and nu5 + nu7. Most of the centrifugal
      distortion constants were constrained to appropriate values, while the
      vibrational term value and three rotational constants in each of the seven
      excited states were adjusted along with Coriolis and Fermi interaction parameters
      by the least-squares analysis of the observed spectrum. The vibration-rotation
      interaction constants alphas thus determined for the nu2 and nu8 states were
      combined with those of other fundamental states already published to calculate
      the equilibrium C-H distance.

PMID- 8980002
TI  - Improved Rotational Constants for KLi Molecule

PMID- 8980001
TI  - Optogalvanic Spectrum of the (000)-(000) Band of the A1A"-X1A' System of HNO
      Using a Ti:Sapphire Laser

PMID- 8980003
TI  - Rotational and Hyperfine Structure of Some Low-J Lines in the A3Phi-X3Delta (0,0)
      Band of TiO

PMID- 8980004
TI  - Dopamine differentiation factors produce partial motor recovery in 6
      hydroxydopamine lesioned rats.
AB  - Two-week infusion of muscle-derived differentiation factor (MDF), or human
      recombinant acidic fibroblast growth factor (aFGF) and/or its muscle-derived
      activating substance into the striatum of unilaterally 6-hydroxydopamine (6-OHDA)
      lesioned rats caused a significant and long lasting (40 days) reduction (48-100%)
      in amphetamine-induced rotational asymmetry. In parallel with behavioural
      recovery, striatal tyrosine hydroxylase (TH) activity, dopamine (DA) and
      dihydroxy-phenyl-acetic acid (DOPAC) levels recovered in a dose-dependent manner
      in all treated rats when compared to controls. The greatest increments were
      observed in rats infused with aFGF and its activator. Increases in biochemical
      indices were not reflected in trophic changes of the dopamine system; thus, the
      number of TH-immunoreactive neurones and their striatal innervation were
      unmodified by treatment with MDF. In contrast with the lesioned brain, infusion
      of these agents into the intact brain produced no change in nigrostriatal
      dopamine biochemistry. Our results suggest that dopamine differentiation factors
      may be important in regulating the production of dopamine in the injured brain
      and, therefore, may be useful in the treatment of DA imbalances associated with
      certain neurological disorders such as Parkinson's disease.

PMID- 8980005
TI  - Expression of the neurofibromatosis I gene product, neurofibromin, in blood
      vessel endothelial cells and smooth muscle.
AB  - Vascular pathology is an underestimated complication of neurofibromatosis 1
      (NF1). Manifestations include renovascular stenosis with associated hypertension,
      cerebrovascular occlusion, visceral ischaemia and aneurysms of smaller arteries.
      This is illustrated by a woman recently evaluated in our Neurofibromatosis
      Program who had multiple cerebrovascular and renovascular abnormalities. To
      determine the contribution of NF1 expression to NF1 vasculopathy, the expression
      of the NF1 gene product, neurofibromin, was examined in blood vessels.
      Neurofibromin was detected in the endothelial cell layer of rat cerebral vessels,
      renal arteries, and aorta by immunohistochemistry. Cultured bovine cerebral
      endothelial cells were found to express NF1 mRNA by RT-PCR and neurofibromin by
      Western immunoblotting and immunocytochemistry. Neurofibromin expression was also
      detected in the smooth muscle layer of the aorta but not of cerebral or renal
      vessels. The vascular abnormalities of NF1 are reviewed and possible pathogenesis
      with respect to neurofibromin expression is discussed.

PMID- 8980006
TI  - Activation of astrocytes during epileptogenesis in the absence of neuronal
      degeneration.
AB  - The issue of whether neuronal degeneration is a primary factor in activation of
      astrocytes during epileptogenesis was addressed using the kindling model of
      epilepsy. No degenerative changes specific to the kindling process were observed
      in brain sections from kindled animals, sampled from the olfactory bulbs through
      to cerebellum and processed with the degeneration-sensitive cupric silver stain.
      Also, examination of lectin-stained sections did not reveal any reactive
      microglia. At the same time, reactive astrocytes, as judged by an increase in
      glial fibrillary acidic protein immunoreactivity and a de novo vimentin
      immunoreactivity, were prominent in amygdala, piriform cortex, entorhinal cortex
      and hippocampus. These results suggest that loss of neurones is not a
      prerequisite for establishment of epilepsy-prone state, that seizures of short
      duration do not necessarily result in neuronal death, and that in kindling,
      astrocytes are activated by factors that are not related to neuronal
      degeneration, but which are likely associated with abnormal neuronal activity.

PMID- 8980007
TI  - Neuroepithelial progenitor cells explanted from human fetal brain proliferate and
      differentiate in vitro.
AB  - Putative neuroepithelial cells were explanted from several germinative zones of
      the brain of 5-to-12 week old human fetuses, obtained from legal abortions. In
      each case, an homogeneous population of neuroepithelial-like cells expressing
      nestin and vimentin was obtained. Cells proliferated in vitro in response to bFGF
      which favoured a neuroblastic differentiation with expression of MAP-5 and beta3
      tubulin. Cells could be maintained and propagated as neuroblasts in serum-free
      medium. The multipotentiality of the cells was revealed by growing them in serum
      containing medium, where a mixed population of cells of the neuronal lineage and
      of glial cells including putative radial glia, astrocytes and oligodendrocytes,
      progressively differentiated. These human progenitor cells proliferating in vitro
      have many potential applications in gene therapy of neurodegenerative diseases.

PMID- 8980008
TI  - Adenovirus mediated gene transfer in organotypic brain slices.
AB  - A replication-defective adenovirus vector carrying the reporter gene encoding
      beta-galactosidase was used to transfect organotypic slices maintained in culture
      for up to 1 month. Three different delivery systems were used to inoculate the
      viral solution, either into the culture medium, or directly onto the surface of
      the slices or by microinjection into the tissue. Using the two first paradigms
      beta-galactosidase expressing cells were mostly of glial phenotype and
      distributed throughout the slices without any specific regional pattern. In
      contrast, microinjection of the adenovirus resulted in a large number of both
      infected neurones and glia, concentrated at the site of injection. This method
      thus appears to be able to circumvent some of the constraints and limitations
      associated with in vivo gene transfer.

PMID- 8980009
TI  - Detection of expanded CAG repeats in bipolar affective disorder using the repeat
      expansion detection (RED) method.
AB  - Genetic factors are of major aetiological importance in Bipolar Affective
      Disorder (BPAD type I and II). The exact mode of inheritance of BPAD is unknown,
      but the recent demonstration of anticipation suggests that dynamic mutations
      could be involved in the clinical expression of the disease. We have used the
      repeat expansion detection (RED) method to test whether the anticipation in BPAD
      could be explained by the presence of expanded trinucleotide repeat sequences.
      Using a (CTG)10 oligonucleotide a significantly higher number of expanded CAG
      repeats were found in the genomic DNA of two independent samples of unrelated
      BPAD patients of Swedish and Belgian ancestry as compared with normal controls.
      The difference in repeat number was more consistent if data of the two samples of
      patients was pooled. In this study a CAG trinucleotide repeat expansion was
      associated for the first time with a major psychiatric disorder. It is possible
      that the CAG trinucleotide repeat expansion is involved in the clinical
      expression of BPAD and that it is the molecular basis explaining the phenomenon
      of anticipation observed in this disorder.

PMID- 8980010
TI  - The utilization of gene targeting to study mammalian neurobiology.

PMID- 8980011
TI  - Re-expression of the intermediate filament nestin in reactive astrocytes.
AB  - The intermediate filament nestin is highly expressed in multipotential stem cells
      of the developing central nervous system (CNS). During neuro- and gliogenesis,
      nestin is replaced by cell type-specific intermediate filaments, e.g.
      neurofilaments and glial fibrillary acidic protein (GFAP). In this study, we
      demonstrate that nestin expression is re-induced in reactive astrocytes in the
      lesioned adult brain. Following ischaemic and mechanical lesioning, a strong and
      sustained expression of nestin was noted in GFAP-positive cells surrounding the
      lesion site. Lesion experiments in transgenic mice carrying the lacZ gene under
      control of regulatory sequences from the nestin gene suggested that the
      upregulation of nestin in reactive astrocytes is mediated via the same sequences
      that control nestin expression during CNS development. These observations and
      recent data on the co-expression of glial and neuronal marker antigens in
      reactive astrocytes point to a close relationship between proliferating
      astrocytes and neuroepithelial precursor cells.

PMID- 8980012
TI  - Selective loss of slow and enhancement of fast Na+ currents in cutaneous afferent
      dorsal root ganglion neurones following axotomy.
AB  - Voltage-dependent Na+ currents were recorded via patch-clamp from identified
      adult rat lumbar cutaneous dorsal root ganglion (DRG) neurones using whole-cell
      and bleb-patch-clamp configurations. Na+ currents in DRG neurones studied 18 days
      after sciatic nerve ligation were compared with those in control neurones.
      Control neurones tended to have a singular kinetically slow Na+ current or net
      Na+ current suggestive of two kinetic varieties of channel in a single neurone.
      Three changes occurred following axotomy: (1) the peak Na+ current increased
      significantly, (2) kinetically slow TTX-resistant Na+ current, which predominated
      in controls, was significantly attenuated or lacking altogether, and (3) a
      singular, TTX-sensitive kinetically fast form of Na+ current predominated. These
      findings suggest that as part of the response to axonal injury, DRG neurones
      increase Na+ channel biosynthesis and/or modify preexisting channels such that
      their kinetics are accelerated. The results are consistent with the idea that
      axotomized DRG neurones become hyperexcitable due to the emergence of a high
      density of kinetically fast, pharmacologically distinguishable, Na+ channels in
      the membrane.

PMID- 8980013
TI  - Critical values for plasma glucose in aggravating ischaemic brain damage:
      correlation to extracellular pH.
AB  - The objective of the present experiments was to characterize conditions under
      which pre-ischaemic hyperglycaemia aggravates brain damage following transient
      forebrain ischaemia. Specifically, we wished to explore whether accentuated
      damage is a threshold function of plasma glucose concentration or pH, as assessed
      by measurements of extracellular pH (pHe). Forebrain ischaemia of 10 min duration
      was induced in rats at varying degrees of hyperglycaemia, with continuous
      measurements of pHe, and the animals were allowed to survive for 7 days before
      histopathological evaluation of the density and distribution of brain damage.
      Ischaemic brain damage appeared as a threshold function of plasma glucose
      concentration. At values of 4-6 mM virtually no damage was observed in any other
      structure than the CA1 sector of the hippocampus and, even in that structure,
      damage was variable. At glucose concentrations of 8-12 mM moderate damage was
      observed infrequently in caudoputamen, parietal cortex, and thalamus. At values
      above 12 mM, damage increased dramatically in these areas, and additional
      structures were recruited in the damage process (cingulate cortex, the CA3 sector
      of the hippocampus, and substantia nigra). Measurements of pHe in parietal cortex
      showed a threshold for seizure induction at values of 6.4-6.5, probably
      corresponding to intracellular pH values of 6.2-6.3. The threshold for
      aggravation of histopathological damage was similar. It is concluded that a
      moderate increase in plasma glucose in the threshold range predisposes the tissue
      to aggravated damage, probably by activating biochemical reactions or
      pathophysiological events with a steep pH dependence.

PMID- 8980014
TI  - Narrow temporal therapeutic window for NMDA antagonist protection against focal
      cerebral ischaemia.
AB  - N-methyl-d-aspartate (NMDA) receptor antagonists have been shown to protect
      against focal cerebral ischaemia when administered either before or soon after
      the onset of ischaemia. However, the precise therapeutic window for protection
      using these drugs remains to be defined. We studied dextrorphan administration
      delayed for 2 or 4 h after transient middle cerebral focal ischaemia in a rabbit
      model. With a 2h delay, the mid (12.5 mg kg-1 h-1) and high doses (17.5 mg kg-1 h
      1) provided significant cortical neuroprotection (50% and 58% reduction,
      respectively), and the low dose (7.5 mg kg-1 h-1) protected against ischaemic
      damage in the basal ganglia (52% reduction). Animals having steady-state serum
      dextrorphan concentrations greater than 2000 ng ml-1 showed 50% cortical
      neuroprotection for the 2-h-delay group. No significant neuroprotection was seen
      in the 4-h-delay group, and the 4 h delay animals with dextrorphan levels greater
      than 2000 ng ml-1 had more severe ischaemic oedema than the saline controls.
      These results suggest a narrow temporal therapeutic window for neuroprotection,
      where delivery of drug delayed by 2 h was efficacious but treatment at 4 h after
      ischaemia onset was not beneficial and possibly harmful. These findings may have
      important implications for the treatment of clinical stroke.

PMID- 8980015
TI  - Delayed histopathological neuronal damage in the substantia nigra compacta
      (nucleus A9) after transient forebrain ischaemia.
AB  - Neurones in the rat substantia nigra compacta (SNC) are initially resistant to
      transient forebrain ischaemia in contrast to vulnerable neurones in the striatum
      that die within 24 h. Animals were exposed to 20 min of four vessel occlusion and
      killed 1 and 3 weeks after reperfusion. All ischaemic animals had striatal
      neurone loss. Analysis of the number of tyrosine hydroxylase immunoreactive
      neurones (THir) in the SNC was comparable between controls and ischaemic animals
      killed 1 week after reperfusion. However, there was a significant reduction in
      THir neurone number (24%), SNC volume (17%), and THir dendritic arborization in
      the substantia nigra reticulata (SNR) that occurred 3 weeks after reperfusion,
      despite the persistence of THir axons in the striatum. Detailed morphological
      analysis of areas distant from the initial ischaemic injury suggest delayed
      degeneration may play an important role in the brain's response to ischaemia, and
      may provide insights for clinical stroke treatment and management.

PMID- 8980016
TI  - The gene defects responsible for familial Alzheimer's disease.
AB  - Four different genes have now been found to contain AD-associated mutations or
      polymorphisms. While the pathogenic mutations in the early-onset FAD genes, APP,
      PS1, and PS2 directly cause AD with nearly 100% penetrance, in a larger subset of
      AD cases with onset over 60 years (maximally for onset at 61-65 years),
      inheritance of the APOE4 allele confers increased risk for AD but is not
      sufficient to cause the disease. Together, these four genes appear to account for
      approximately 50% of FAD cases. We are actively screening the genome for
      additional FAD loci by genotyping markers in over 400 FAD nuclear pedigrees and
      affected sib-pairs (83% late-onset and 17% early-onset). We have recently
      discovered genetic linkage to a novel FAD locus on chromosome 12 as well as
      another putative locus on chromosome 3 (unpublished findings). Positional cloning
      strategies are currently under way to identify these potentially novel FAD genes.
      A common event which is associated with all of the known FAD genes is the
      excessive accumulation of the A beta peptide and deposition of beta-amyloid in
      the brain. Thus, a common pathogenic pathway for AD neuropathogenesis appears to
      center around the cellular trafficking, maturation, and processing of APP, and
      the subsequent generation, aggregation, and deposition of A beta (or more
      specifically, A beta 1-42). APP and presenilin gene mutations most likely act as
      either gain-of-function or dominant negative gene defects which may ultimately
      lead to the transport of APP into intracellular compartments that promote the
      enhanced production of A beta or A beta 1-42. AD patients who carry an APOE4
      allele experience increased amyloid burden in their brains compared to APOE4
      negative AD cases. Thus, the presence of APOE4 would also appear to lead to
      abnormal generation, aggregation, or clearance of A beta in the brain A beta,
      perhaps by working in concert with its neuronal receptor, LRP. While the exact
      mechanisms by which the known FAD gene changes lead to the onset of AD remain
      unclear, the available data indicate that novel therapies aimed at curbing the
      generation, aggregation, and deposition of A beta would appear to carry the
      greatest potential for the effective treatment of this formidable disease.

PMID- 8980017
TI  - beta-Amyloid protein precursor in Microcebus murinus: genotyping and brain
      localization.
AB  - Senile plaques characterized by beta-amyloid protein (A beta) deposits around
      dystrophic neurites and glial cells are more abundant in the cerebral cortical
      parenchyma of Alzheimer's disease (AD) patients than in the aged population. Four
      different mutations in the amyloid precursor protein (APP) gene have been
      directly involved in a few cases of familial AD with early onset (before 60
      years). Previous studies have shown that Microcebus murinus, a nonhuman primate,
      also develops analogous deposits of A beta in the cortical parenchyma and blood
      vessel walls in the brain. Sequence analysis of exons 16 and 17 of the APP gene,
      encoding for A beta, revealed that even if nucleotide divergences occurred, the
      resulting peptide is completely homologous with the human A beta. The systematic
      comparison of the A beta nucleotide sequence in microcebus with or without
      amyloid deposits revealed that neither the presence of mutations involved in some
      cases of early onset familial AD nor the presence of a mutational founder effect
      can explain the amyloidosis observed in some old microcebus of our breeding.
      Localization of the APP was performed by immunocytochemistry in the brains of
      adult microcebus (1 to 11 years of age) using two antibodies raised against the C
      terminus and N-terminus portions of APP. Microscopic examinations revealed that
      in the microcebus the APP distribution was similar to that observed in the human:
      (1) A beta and its precursor were simultaneously observed in amyloid plaques (AP)
      of the cortical parenchyma; (2) APP was localized in cell bodies and proximal
      dendrites of neurons, in astrocytes and oligodendrocytes, and in blood vessel and
      capillary walls; (3) labeling of APP in these structures was correlated with the
      presence of AP; and (4) labeling of APP increased with the age of the animal.

PMID- 8980018
TI  - Differential expression of normal and mutant Huntington's disease gene alleles.
AB  - Huntingtin expression was examined by Western blot and immunoprecipitation
      studies of lymphoblastoid cell lines from Huntington's disease (HD) homozygotes,
      heterozygotes, and a phenotypically normal individual with a t(4p16.3;12p13.3)
      breakpoint in the HD gene. The latter produced a reduced level of normal
      huntingtin without evidence of an altered protein, indicating that simple loss of
      huntingtin activity does not cause HD. In juvenile onset HD heterozygotes, NH2-
      and COOH-terminal antisera revealed reduced relative expression from the mutant
      allele. Pulse-chase studies indicated that huntingtin is a stable protein whose
      differential allelic expression is not due to destabilization of the mutant
      isoform. No stable breakdown products specific to mutant huntingtin were detected
      in either HD homozygotes or heterozygotes. These data are consistent with HD
      involving either a gain of function or a dominant negative loss of function that
      operates within severe constraints and suggest that in either case the pathogenic
      process is usually saturated by the amount of abnormal huntingtin produced from a
      single mutant allele.

PMID- 8980019
TI  - Detection of scrapie agent in the peripheral nervous system of a diseased sheep.
AB  - In an attempt to determine whether scrapie infectivity can be found in the
      peripheral nervous system of a scrapie-diseased sheep, mice were inoculated
      intracerebrally or intraperitoneally with 10-fold dilutions of homogenates of
      Nervus (N.) axillaris, N. ulnaris, N. medianus, N. ischiadicus, N. tibialis, N.
      fibularis, and N.saphenus. Mice were observed for clinical signs of scrapie for
      700 days and their brains were analyzed for accumulation of pathological prion
      protein by immunoblot. Substantial amounts of infectivity were found in all
      peripheral nerves tested except N.saphenus. Infectivity at titers of
      approximately 10(4.5) mouse infectious units (MIU)/g were detected in N.
      axillaris and N. ischiadicus, of approximately 10(3.0) MIU/g in N. ulnaris, N.
      medianus, N. tibialis, and N.fibularis, and of 10(6) MIU/g in the cerebellum.
      Since muscles are traversed by the nerve tracts tested, mutton of scrapie
      diseased animals should not be regarded as being free of scrapie agent.

PMID- 8980020
TI  - Hereditary deficiencies in complement C5 are associated with intensified
      neurodegenerative responses that implicate new roles for the C-system in neuronal
      and astrocytic functions.
AB  - Possible roles of the complement (C) system in the normal and injured brain were
      explored with inbred mice that carried a frameshift mutation in the C5 gene. A
      congenic pair was used: the C5-sufficient (C5+) B10.D2/nSnJ strain with the
      functional allele (Hc1) from the C57BL/10J donor strain was compared with the C5
      deficient (C5-) B10.D2/oSnJ with the Hc0 allele from the C5-deficient DBA/2J
      donor strain. In response to the excitotoxin kainic acid (KA), C5- mice had more
      hippocampal pyramidal neuron death and greater induction of astrocyte mRNAs
      (GFAP, apoE, apoJ). In primary astrocyte cultures from unlesioned mice, an
      inflammatory stimulus (LPS) caused greater production of IL-6 and TNF production
      in C5- mice. These enhanced responses to KA and LPS suggest that hereditary C5
      deficits modify responses to neurodegenerative stimuli of neurons and astrocytes.
      Moreover, unlesioned C5- mice had smaller input-output slopes for the NMDA
      component of the EPSP amplitude, but enhanced the Ca(+2)-dependent AMPA binding.
      Thus, C5 deficits also modify basal properties of glutamatergic neurotransmission
      that pertain to synaptic plasticity. These findings are also discussed in
      relation to roles of the C-system in Alzheimer disease (AD). C5 deficiencies may
      also be considered in the choice of strains as transgene hosts and for genetic
      analysis of normal and pathological brain functions. In recent transgenic studies
      for AD, C5- hosts showed greater neurodegeneration, consistent with the present
      data. These pleiotropic associations of C5 deficiency indicate roles for the C
      system in neurodegeneration, but also in normal neural functions.

PMID- 8980021
TI  - Cutaneous innervation density in the allodynic form of postherpetic neuralgia.
AB  - The relationship between deafferentation, sensory function, and pain was explored
      in 18 subjects with chronic postherpetic neuralgia (PHN). Subjective thresholds
      for warmth, cooling, and heat pain were measured quantitatively in painful skin
      areas and compared with normal contralateral skin. The severity of allodynia was
      graded in the affected area. Two 3-mm punch biopsies were taken from the most
      painful skin area and one from unaffected contralateral mirror-image skin.
      Immunofluorescence with the axonal marker PGP 9.5 revealed a reduction in density
      of innervation of the epidermis, the dermal-epidermal junction, and the eccrine
      sweat glands in PHN skin. In painful PHN skin, the reduction in innervation
      density was positively correlated with the magnitude of the thermal sensory
      deficits. However, loss of cutaneous innervation was inversely correlated with
      allodynia, indicating that surviving cutaneous primary afferent nociceptors that
      are spontaneously active and/or sensitized contribute to PHN pain and allodynia.

PMID- 8980022
TI  - Rapid alterations in dendrite morphology during sublethal hypoxia or glutamate
      receptor activation.
AB  - Selective degeneration of postsynaptic neuronal dendrites is a pathological
      hallmark of brain injury in stroke and other neurological disorders. We examined
      dendritic injury in primary cultures dissociated from mouse neocortex. Neuronal
      morphology was visualized using the fluorescent membrane tracer, Dil, or
      immunofluorescence with antibodies to the dendrite-specific microtubule
      associated protein, MAP2. Deprivation of oxygen and glucose for 30-60 min
      resulted in segmental dendritic beading, or varicosities, and loss of dendritic
      spines. This pattern of dendritic injury was blocked by addition of selective
      NMDA antagonists, and was reproduced within 5 min of exposure to 10-100 microM
      NMDA. Widespread dendritic varicosity formation occurred even with exposures to
      oxygen-glucose deprivation or NMDA which resulted in little neuronal death by the
      following day. Despite marked structural changes affecting virtually all neurons,
      dendrite shape returned to normal within 2 h of terminating sublethal oxygen
      glucose deprivation or NMDA application. Rapid, reversible changes in dendritic
      structure may contribute to alterations in neuronal function following glutamate
      receptor stimulation under physiological or pathological conditions.

PMID- 8980023
TI  - Human apolipoprotein E2, E3, and E4 isoform-specific transgenic mice: human-like
      pattern of glial and neuronal immunoreactivity in central nervous system not
      observed in wild-type mice.
AB  - Apolipoprotein E (apoE) and its three major alleles (APOE2, E3, and E4) have been
      implicated in Alzheimer's disease and other neurological disorders. Little is
      known of the role apoE plays in normal brain function and pathology. To create a
      model to study apoE in brain, we have generated APOE transgenic mice using
      microinjection of allele-specific human genomic fragments to establish founders
      which were then bred to APOE knockout mice lacking a functional mouse apoE
      protein. This allows the study of apoE without interference from the endogenous
      mouse APOE gene. Results demonstrate that transgenic lines have been established
      that transcribe and express apoE appropriately in brain, liver, and other
      tissues. High cholesterol levels found in APOE knockout mice are substantially
      corrected in the APOE transgenic lines. ApoE immunoreactivity has been detected
      in glial cells and selected classes of neurons in all three isoform-specific
      transgenics. This pattern of immunoreactivity is similar to that observed in
      nonhuman primates and man, and contrasts with the strictly glial staining pattern
      of normal rodents.

PMID- 8980024
TI  - Factors Influencing Pyrethroid Resistance in a Permethrin-Selected Strain of the
      Soybean Looper, Pseudoplusia includens (Walker)
AB  - Cytochrome P450 monooxgenase activity toward p-nitroanisole was measured in
      larvae of three strains of soybean looper, Pseudoplusia includens (Walker),
      including a laboratory susceptible (S) strain, a resistant (R) strain selected
      for several generations with permethrin, and a nonselected (NS) strain from the
      same field collections as the R strain. Activity was significantly higher in R
      strain larvae than in the S and NS strains (1.8- and 1.4-fold, respectively), and
      there was no significant difference between activity in the S and NS strains.
      Resistance to the alpha-cyano pyrethroids deltamethrin and cypermethrin was
      similar to or higher than that observed with permethrin (RR = 70.0, 62.4, 145.3
      and 12.1, 32.3, and 27.0 for permethrin, deltamethrin, and cypermethrin in R and
      NS strains, respectively). The R strain was less resistant (RR = 4.3) to
      tefluthrin, a pyrethroid with a fluorinated-phenyl alcohol moiety, and a nonester
      (ether) pyrethroid, BRC 429 (RR = 17.7). Piperonyl butoxide (PB) significantly
      increased the toxicity of each insecticide tested in the R and NS strains. In
      addition, penetration of 14C-cypermethrin was decreased significantly at 24 hr
      after treatment when R strain larvae were pretreated with PB, with 21.1% of the
      applied dose unpenetrated in PB-treated larvae and 7.6% unpenetrated in larvae
      not treated with PB.

PMID- 8980025
TI  - Insecticide and Insecticide Metabolite Interactions with Cytochrome P450 Mediated
      Activities in Maize
AB  - In vitro assays were used to determine if organophosphate, carbamate, and
      synthetic pyrethroid insecticides affected the cytochrome P450 monooxygenase
      (P450) catalyzed hydroxylation of nicosulfuron, bentazon, cinnamic acid, or
      lauric acid in maize microsomes. All P450 activities were inhibited approximately
      50% by carbaryl, and none were inhibited by permethrin. Hydroxylations of
      nicosulfuron, bentazon, lauric acid, and cinnamic acid were inhibited by
      malathion 83, 92, 38, and 0%, respectively. Terbufos was only moderately (36%)
      inhibitory of in vitro P450 hydroxylation of nicosulfuron. Nicosulfuron
      hydroxylation was more sensitive than bentazon hydroxylation to inhibition by the
      insecticides, and both herbicide hydroxylations were more sensitive than lauric
      acid or cinnamic acid hydroxylations to the insecticides. Since the oxidative
      metabolites of terbufos were shown to be more potent inhibitors of in vivo
      nicosulfuron metabolism than terbufos, we examined the effect of terbufos-sulfone
      on in vivo and in vitro herbicide metabolism. Terbufos-sulfone inhibited
      metabolism of nicosulfuron and imazethapyr, but not bentazon, in excised corn
      shoots. Microsomal hydroxylation of nicosulfuron, bentazon, chlorimuron ethyl,
      and imazethapyr, as well as the desulfuration of malathion, were strongly
      inhibited (>65%) by terbufos-sulfone. Cinnamic acid hydroxylase appeared to be
      different from the P450(s) responsible for the pesticide metabolism as it was not
      inhibited by terbufos-sulfone. However, the data also suggest that malathion,
      nicosulfuron, bentazon, chlorimuron ethyl, and imazethapyr all share a P450 in
      common with terbufos-sulfone. Alternatively, there may be separate P450s for the
      metabolism of the herbicides and malathion, all of which also metabolize terbufos
      sulfone. These data show that the inhibition of P450 hydroxylation of
      nicosulfuron by terbufos-sulfone can explain the injury when maize is exposed to
      both terbufos and nicosulfuron. However, the insecticides that are the most
      potent in vitro P450 inhibitors are not necessarily the ones that cause the most
      herbicide injury in the field.

PMID- 8980026
TI  - Insensitive Acetylcholinesterase and Resistance to Thiodicarb in Australian
      Helicoverpa armigera Hubner (Lepidoptera: Noctuidae)
AB  - Thiodicarb resistance was diagnosed in a field strain of Helicoverpa armigera
      from Tamworth, New South Wales in March 1993. This is the first record of H.
      armigera resistance to thiodicarb. Bioassays after selection in the laboratory
      indicated that the thiodicarb resistance factor was greater than 40-fold and was
      associated with cross resistance to methomyl. Insensitive acetylcholinesterase
      was identified as a resistance mechanism. Potential resistance management tactics
      and opportunities for biochemical resistance monitoring are discussed.

PMID- 8980027
TI  - Lipid Peroxidation and Membrane Disruption by Vinclozolin in Dicarboximide
      Susceptible and -Resistant Isolates of Botrytis cinerea
AB  - A dicarboximide-susceptible (DS) isolate and a dicarboximide-resistant (DR)
      isolate of Botrytis cinerea were compared with regard to spore germination,
      mycelial growth, cellular leakage, and lipid peroxidation upon treatment with the
      dicarboximide fungicide vinclozolin. The fungicide inhibited spore germination
      and mycelial growth of the DS isolate, but not those of the DR isolate. The
      inhibitory effect of the fungicide was greater on mycelial growth than on spore
      germination of the DS isolate. Significant cellular leakage from the fungicide
      treated DS or DR isolate began to increase after 24 hr incubation, depending on
      the concentration of the fungicide and the duration of incubation time. However,
      the magnitude of cellular leakage was much greater from the DS isolate than from
      the DR isolate. Vinclozolin caused considerable lipid peroxidation in the DS
      isolate, whereas little or no lipid peroxidation occurred in the DR isolate
      treated with the fungicide. Lipid peroxidation preceded cellular leakage from the
      DS isolate following fungicide treatment. The effects of the fungicide on
      mycelial growth, cellular leakage, and lipid peroxidation of the DS isolate were
      all reversed by the addition of alpha-tocopherol to the incubation medium. These
      results demonstrate that vinclozolin causes significant lipid peroxidation and
      subsequent cellular leakage from a DS isolate, but not from a DR isolate.
      Furthermore, they suggest that the mechanism of action of dicarboximide
      fungicides is associated with membrane lipid peroxidation.

PMID- 8980028
TI  - Interaction of Lindane Isomers with Chloride Currents in Insect Membranes: Steric
      Requirements for Channel Modulation and Block
AB  - Electrophysiological methods were used to characterize the modulatory effects of
      hexachlorocyclohexane isomers on GABA-activated chloride currents in dissociated
      locust neurones. Conductance changes associated with hyperpolarising responses
      (or outward voltage-clamped currents), evoked by brief GABA pulses, were
      inhibited by the gamma-isomer at 0.01-1 &mu;M. The antagonistic action was
      noncompetitive and voltage-independent: the concentration required for half
      maximal block was <0.01 &mu;M. The rate of equilibration with the
      membrane/receptor was inversely proportional to the concentration applied and was
      not dependent upon agonist-induced channel gating: effects were only partially
      reversible with extensive washing. In contrast the noninsecticidal beta-isomer
      was a low-affinity (>/=10 &mu;M) positive modulator of the inhibitory chloride
      channels. The modulatory action was voltage-dependent (more pronounced for inward
      currents at hyperpolarised potentials), did not reflect changes in chloride
      equilibrium potential, and was completely reversible. Nicotinic acetylcholine
      receptors were consistently antagonised by the beta-isomer at 10 &mu;M. The above
      results were interpreted by computer-assisted modelling and are discussed in the
      context of a pharmacophore model for picrotoxinin and convulsant insecticides.
      The gamma-isomer overlays well with picrotoxinin and a convulsant butyrolactone
      whereas the beta-isomer and anticonvulsant butyrolactones conform to a different
      template. Liganding mechanisms and comparative/species differences in chloride
      channel pharmacology are discussed in the context of potential for development of
      invertebrate-selective pesticides.

PMID- 8980029
TI  - Flupoxam Induces Classic Club Root Morphology but Is Not a Mitotic Disrupter
      Herbicide
AB  - Flupoxam, an herbicide representative of a powerful new class of herbicides
      intended for control of broad-leaved weeds in cereals, has been identified as a
      mitotic disrupter herbicide. Flupoxam was evaluated on watercress seedlings for
      evidence of antimicrotubule effects characteristic of mitotic disrupter
      herbicides. At 1 &mu;M, flupoxam inhibited root elongation and induced club root
      morphology. However, examination by light microscopy and tubulin
      immunofluorescent microscopy revealed that flupoxam is not a mitotic disrupter
      herbicide.

PMID- 8980030
TI  - Mechanism of Safening Action of Dymuron and Its Two Monomethyl Analogues against
      Bensulfuron-methyl Injury to Rice (Oryza sativa)
AB  - The comparative efficacy and mechanism of action of the herbicide dymuron and its
      two optically active monomethyl analogues, (R)-1-(alpha-methylbenzyl)-3-(p
      tolylurea) (R-MBTU) and S-MBTU, as safeners of rice against injury from
      bensulfuron-methyl were investigated. Bioassays using etiolated seedlings of rice
      (Oryza sativa L., cv. Lemont), grown either in agar or in liquid media containing
      bensulfuron-methyl, showed that this sulfonylurea herbicide is a potent inhibitor
      of rice root growth (I50 = 120 nM). Similar studies with the herbicide dymuron
      and its two optically active monomethyl analogues (R-MTBU and S-MTBU) showed that
      at 10 &mu;M, dymuron and R-MBTU reduced rice root length by 25 and 17%,
      respectively, whereas S-MBTU had no effect on root growth of Lemont rice.
      Combined treatments with bensulfuron-methyl and dymuron or each of its two
      analogues confirmed that S-MTBU is an excellent safener of rice against
      bensulfuron-methyl, far more effective than either dymuron or R-MTBU. The
      protective action of S-MTBU appeared to result mainly from a drastic reduction in
      the uptake of bensulfuron-methyl by safened rice seedlings. Dymuron and R-MTBU
      reduced also the uptake of bensulfuron-methyl by rice seedlings, but to a lesser
      extent than S-MTBU. Quantitative changes in the metabolism of bensulfuron-methyl
      by safened rice seedlings were also observed, but did not appear to support the
      involvement of enhanced herbicide metabolism in the safening action of S-MBTU, R
      MBTU, and dymuron. The major metabolites of bensulfuron-methyl detected in both
      safened and unsafened rice seedlings were tentatively identified as methyl-(4
      hydroxy-6-methoxypyrimidin-2-yl-carbamoylsulfamoyl)-o-toluate; methyl
      (aminosulfonyl)-o-toluate; and 1H-2,3-benzothiazin-4-(3H)-one-2,2-dioxide.

PMID- 8980031
TI  - Stimulation of Phosphoinositide Hydrolysis by gamma- and delta
      Hexachlorocyclohexane in Primary Cultures of Cerebellar Granule Cells:
      Interaction with Glutamate and Carbachol Receptor-Mediated Phosphoinositide
      Response and Effects of Specific Pharmacological Agents
AB  - The accumulation of [3H]inositol phosphates derived from phosphoinositide
      hydrolysis stimulated by gamma- and delta-hexachlorocyclohexane isomers was
      characterized in primary cultures of cerebellar granule cells. The EC50 for gamma
      and delta-hexachlorocyclohexane was 106 and 85 MUM, respectively. Stimulatory
      effects of hexachlorocyclohexane isomers were highly dependent on extracellular
      Ca2+ but they were not inhibited by classical voltage-sensitive Ca2+ and Na+
      channel blockers. The Na+/Ca2+ exchanger blocker amiloride caused a significant
      inhibition of delta-hexachlorocyclohexane effects. A lack of additive effects on
      phosphoinositide hydrolysis stimulation between hexachlorocyclohexane isomers and
      depolarization by high K+ was observed. The effects of each hexachlorocyclohexane
      isomer on glutamate or carbachol-induced inositol phosphate stimulation were also
      not additive, whereas that of high K+ was less than additive or synergistic when
      combined with glutamate or carbachol, respectively. When neuronal cells were
      exposed to the combination of delta-hexachlorocyclohexane and glutamate or
      carbachol in the presence of the respective receptor antagonists only the delta
      hexachlorocyclohexane stimulatory effect was observed. Thus, the inhibition of
      glutamate- and carbachol-stimulated phosphoinositide hydrolysis by delta
      hexachlorocyclohexane seems to imply a receptor-independent mechanism. It is
      suggested that both gamma- and delta-hexachlorocyclohexane activate
      phosphoinositide-specific phospholipase C partly through Ca2+-related mechanisms.

PMID- 8980032
TI  - Protoporphyrinogen Destruction by Plant Extracts and Correlation with Tolerance
      to Protoporphyrinogen Oxidase-Inhibiting Herbicides
AB  - Herbicidal damage by photobleaching diphenylether herbicides is the indirect
      result of inhibition of an enzyme in chlorophyll biosynthesis. The substrate of
      the inhibited enzyme, protoporphyrinogen, accumulates and is subsequently
      converted to protoporphyrin, a potent photoactive compound which causes light
      dependent membrane damage. In the present study, we report characteristics of a
      factor in the soluble fraction of leaves which can decompose protoporphyrinogen
      to nonporphyrin products. This process may be important in protecting plants from
      herbicide damage, since it would interfere with accumulation of the phototoxic
      porphyrin, protoporphyrin. We found that this protoporphyrinogen destruction is
      associated with the protein fraction of the soluble leaf homogenate, suggesting
      its enzymatic nature. Protoporphyrinogen destruction is stable to mild heat, but
      is eliminated by boiling. Protoporphyrinogen destruction is present in the
      soluble leaf homogenate but is not localized within the stromal fraction of the
      chloroplast. The reductants dithiothreitol and beta-mercaptoethanol, but not
      glutathione, inhibit protoporphyrinogen destruction at high concentrations. In
      contrast, ascorbic acid markedly inhibits destruction even at low concentrations,
      suggesting a role for cellular ascorbic acid in protecting protoporphyrinogen
      from destruction, thereby enhancing herbicide action. Protoporphyrinogen
      destruction was least active in young cucumber leaves, a plant highly susceptible
      to herbicides. Higher levels of protoporphyrinogen destruction were found in
      leaves of broadleaf mustard and radish, two plants exhibiting herbicide
      tolerance. For cucumber, the extent of destruction increased with the age of the
      plant. These findings suggest a correlation between increased protoporphyrinogen
      destruction and herbicide tolerance in some plant species.

PMID- 8980033
TI  - Comparison of an Esterase Associated with Organophosphate Resistance in Lucilia
      cuprina with an Orthologue Not Associated with Resistance in Drosophila
      melanogaster
AB  - Orthologous E3 and EST23 carboxylesterases have been enriched over 200-fold from
      organophosphate (OP) susceptible strains of Lucilia cuprina and Drosophila
      melanogaster, respectively. Mutants of E3 are associated with OP resistance but
      no resistance mutations of EST23 are known. The behaviours of the two enzymes
      were very similar during purification which involved differential centrifugation
      followed by three or four ion exchange and gel filtration chromatographic steps.
      Nondenaturing polyacrylamide gel electrophoresis and histochemical staining for
      esterase activity revealed no other esterases in the enriched material. Two
      dimensional polyacrylamide gel electrophoresis (native followed by denaturing)
      showed that a major 70-kDa component of each preparation comigrates with E3 and
      EST23 activities, respectively. Kinetic properties of the enzymes are also very
      similar. Estimates of Km, Kcat, and Kcat/Km for alpha-naphthyl acetate are 42 +/-
      18 &mu;M, 19 sec-1, and 4.6 x 10(5) M-1 sec-1, respectively, for E3, and 62 +/-
      25 &mu;M, 23 sec-1, and 3.7 x 10(5) M-1 sec-1, for EST23. Both enzymes are
      potently inhibited by dibrom and less potently by another OP,
      diisopropylflurophosphate. E3 is also potently inhibited by paraoxon, whereas
      EST23 is at least 8-fold less susceptible to inhibition by paraoxon. This
      supports previous analyses of crude homogenates which showed that E3 is more
      susceptible to inhibition by paraoxon and fenitrooxon than is EST23 or the target
      site for OP action, acetylcholinesterase. It is proposed that the unusual
      affinity of E3 for such OPs is a necessary precondition for mutations that enable
      it to confer OP resistance on L. cuprina.

PMID- 8980034
TI  - A Point Mutation of Acetylcholinesterase Associated with Azinphosmethyl
      Resistance and Reduced Fitness in Colorado Potato Beetle
AB  - A serine to glycine point mutation of acetylcholinesterase (AChE, EC 1.1.1.7) was
      identified in an azinphosmethyl-resistant strain of Colorado potato beetle
      [Leptinotarsa decemlineata (Say)]. The position of the mutation corresponds to
      Val 238 of the Torpedo AChE and represents the first amino acid residue to form
      the alpha-helix, alpha-E'1. The predicted secondary structure of the mutation
      containing region of AChE suggested that the transition from the turn to the
      alpha-helix occurs sooner in the sequence when serine is replaced by glycine.
      Thus, conformational changes in the AChE due to the alpha-helix deformation were
      expected to impinge upon both the catalytic and the peripheral binding sites,
      resulting in the modification of the bindings of organophosphorus insecticides
      and other ligands to these sites. The mutation appeared to be associated with the
      fitness of the beetle. The intrinsic rate of increase of the azinphosmethyl
      resistant (AZ-R) strain was relatively low when the beetles were reared on the
      Russet Burbank potato cultivar, but was relatively high when they were reared on
      the NDA 1725-1 potato cultivar. Because these two potato cultivars contain
      different amounts of steroidal glycoalkaloids (e.g., alpha-solanine and alpha
      chaconine), the different fitness of the AZ-R strain on different potato
      cultivars may be partially attributed to the increased sensitivity of the
      azinphosmethyl-resistant form of AChE to the inhibition by alpha-solanine and
      reduced sensitivity to alpha-chaconine as previously reported.

PMID- 8980035
TI  - Monooxygenase, Esterase, and Glutathione Transferase Activity Associated with
      Azinphosmethyl Resistance in the Tufted Apple Bud Moth, Platynota idaeusalis
AB  - Azinphosmethyl-selected tufted apple bud moths were compared to susceptible and
      reverted strains with respect to possible metabolic mechanisms of resistance
      within the third instar, fifth instar, and adults. Based upon bioassays conducted
      by topical application with azinphosmethyl, LD50s were as high as 867-fold in the
      selected strain as compared to that seen in susceptible bud moths. The LD50 of
      the reverted strain was intermediate to that of the susceptible and selected
      insects at all stages studied. Glutathione transferase activity measured with 1
      chloro-2,4-dinitrobenzene was elevated in the selected strain 1.6- and 2.2-fold
      as compared to third and fifth stadium susceptible bud moths, respectively. No
      consistent strain differences were noted for 1,2-dichloro-4-nitrobenzene.
      Cytochrome P450 content and P450 mRNA was not significantly different in fifth
      instars of the susceptible and selected strain. However, there was a 2.7- and 1.9
      fold increase in benzphetamine and p-nitroanisole metabolism, respectively, in
      the guts of azinphosmethyl-selected fifth instars. Benzo[a]pyrene metabolism was
      elevated 2.4-fold in the carcass of selected bud moths and no differences were
      noted for methoxyresorufrin in either gut or carcass. Susceptible fifth instars
      demonstrated a reduced rate of metabolism of azinphosmethyl to the oxon and
      methyl benzazamide. Piperonyl butoxide failed to synergize azinphosmethyl
      toxicity. Esterase activity measured with 1-naphthyl acetate and p-nitrophenyl
      acetate was elevated in selected larvae compared to that seen in susceptible
      tufted apple bud moths in both larvae and adults. This increased esterase
      activity was attributed to several isoforms as resolved by analytical isoelectric
      focusing. One of these forms was consistently overexpressed in all of the life
      stages examined. Pretreatment of selected fifth instars with S,S,S
      tributylphosphorotrithioate increased the toxicity of azinphosmethyl 400-fold and
      had minimal effect on toxicity in susceptible insects. It appears that multiple
      hydrolases are the primary metabolic factor in azinphosmethyl resistance in the
      tufted apple bud moth.

PMID- 8980036
TI  - Determination of Ace.1 Genotypes in Single Mosquitoes: Toward an Ecumenical
      Biochemical Test
AB  - The occurrence of two acetylcholinesterases, AChE1 and AChE2, in the mosquito
      Culex pipiens has been recently documented. Resistance to organophosphates and
      carbamates due to target insensitivity is the result of a qualitative change of
      only AChE1, encoded by the Ace.1 gene. Because AChE1 and AChE2 differ in their
      sensitivity to inhibitors, Ace.1 genotypes can be misclassified by previous
      tests. We describe a new rapid microplate test that allows unambiguous
      identification of Ace.1 genotypes. This test involves comparing AChE activities
      in the absence of insecticide and in the presence of two propoxur concentrations:
      a low concentration that inhibits only the sensitive AChE1 and a higher
      concentration that inhibits also AChE2 but not the insensitive AChE1 responsible
      of insecticide resistance. This comparison allows the identification of the three
      Ace.1 genotypes: resistant (Ace.1RR), susceptible (Ace.1SS) homozygotes, and
      heterozygotes (Ace.1RS). The similarity of propoxur sensitivity of modified
      AChE1s found in various resistant strains from the United States, Europe, and
      Africa indicates that this test is probably suitable for all the Ace.1 alleles
      described so far in C. pipiens.

PMID- 8980037
TI  - Susceptibilities of Different Test Systems from Maize (Zea mays), Poa annua, and
      Festuca rubra to Herbicides That Inhibit the Enzyme Acetyl-Coenzyme A Carboxylase
AB  - The susceptibilities of maize (Zea mays cv. Champ) and two graminicide-resistant
      grass species, Poa annua (annual meadow grass) and Festuca rubra (red fescue), to
      two aryloxyphenoxypropionates (quizalofop and fluazifop) and a cyclohexanedione
      (sethoxydim) graminicide were evaluated in leaf blades and isolated chloroplasts,
      and by assaying acetyl-coenzyme A carboxylase (ACCase) in desalted leaf
      homogenates. The graminicide resistance of P. annua and F. rubra appeared to be
      at the level of ACCase. Festuca rubra ACCase was highly insensitive and P. annua
      ACCase was partially insensitive to the graminicides that were tested. Fatty acid
      synthesis in isolated maize chloroplasts was more susceptible to inhibition than
      was ACCase activity from whole leaves. There was a smaller difference in
      graminicide sensitivity between these two test systems in P. annua. The
      developmental pattern of ACCase specific activity and its inhibition by
      quizalofop was measured in maize and P. annua leaf blades. There was an age
      dependent increase in the sensitivity of maize leaf ACCase activity to inhibition
      by quizalofop. Together with the greater susceptibility of chloroplasts compared
      with leaf homogenates this could imply that a graminicide-insensitive
      (extrachloroplastic) ACCase isoform is less highly expressed in older leaves. Poa
      annua ACCase did not significantly alter in sensitivity as leaves aged,
      consistent with the smaller difference in the level of inhibition between
      chloroplasts and leaf homogenates in this species. A small pyruvate carboxylase
      activity was detected in maize leaves after 9 days. By 38 days, when leaves were
      senescing, pyruvate carboxylase activity predominated over ACCase.

PMID- 8980038
TI  - Impact on Salivary Gland Degeneration by Putative Ecdysteroid Antagonists and
      Agonists in the Ixodid Tick Amblyomma hebraeum
AB  - Ecdysteroids cause salivary gland degeneration in female ixodid ticks. We tested
      the effects of the following compounds on salivary gland degeneration in the
      ixodid tick Amblyomma hebraeum Koch: HHCS (22S,23S-homocastasterone), SSBR
      (22S,23S-homobrassinolide), STGM (2alpha,3alpha(OH)2-Delta22-stigmasten-6-one),
      RH 5849, and RH 5992. The first three are brassinosteroids (putative ecdysone
      antagonists) and the last two are nonsteroidal mimics of ecdysone in a variety of
      insects. In vitro, HHCS (up to 4 &mu;g/ml, 8.4 &mu;M) did not attenuate
      degeneration caused by 20-hydroxyecdysone; on the contrary, it enhanced the
      degree of salivary gland degeneration. SSBR (up to 4.5 &mu;g/ml, 9 &mu;M)
      likewise did not reduce 20-hydroxyecdysone mediated degeneration. RH 5849 up to
      15 &mu;g/ml (51 &mu;M) and RH 5992 up to 10 &mu;g/ml (28 &mu;M) had no ecdysone
      mimicking effect. In vivo, both RH compounds had an ecdysone-mimicking effect. RH
      5849 (but not RH 5992) at 10 &mu;g/tick increased ovary wet weight slightly. None
      of the brassinosteroids displaced a significant amount of [3H]ponasterone A (PoA)
      from the ecdysone receptor at 6 &mu;g/ml (12-14 &mu;M) or below. RH 5849 (14
      &mu;g/ml, 47 &mu;M) displaced 8% of (PoA) binding; at 68 &mu;g/ml (230 &mu;M)
      displacement was 30%. For RH 5992 inhibition of PoA binding was 16, 33, and 43%
      at 4.5, 16, and 79 &mu;g/ml (13, 45, and 79 &mu;M), respectively. Overall, the
      brassinosteroids and the RH compounds do not act on the tick salivary gland
      ecdysteroid system in a way similar to the way they act on some insect systems.

PMID- 8980039
TI  - Cytochrome b5 Is Essential for Cytochrome P450 6D1-Mediated Cypermethrin
      Resistance in LPR House Flies
AB  - Cytochrome P450 monooxygenase-mediated detoxification is a very important
      mechanism of resistance to insecticides. In the LPR strain of house fly, the
      major mechanism of resistance to pyrethroids is monooxygenase-mediated metabolism
      due to the overexpression of cytochrome P450 6D1 (CYP6D1). Although the role of
      CYP6D1 in pyrethroid resistance has been demonstrated, there is no information as
      to whether cytochrome b5 is involved in this reaction and what the major CYP6D1
      specific metabolite is. Using a cytochrome b5 antiserum we demonstrate that
      cytochrome b5 is required for the elevated level of CYP6D1-mediated cypermethrin
      metabolism observed in microsomes from the resistant LPR strain compared to a
      susceptible strain. Therefore, cytochrome b5 is directly involved in this
      monooxygenase-mediated resistance. NADH has no significant effect on this
      metabolism, suggesting that in vitro the second electron source for CYP6D1 is
      NADPH when cypermethrin is the substrate. Using GC-MS, the primary CYP6D1
      specific metabolite formed in vitro was identified as 4'-OH cypermethrin.

PMID- 8980057
TI  - A Study of Solvation-Shell Symmetry in Electrolyte Solutions Using Quadrupolar
      NMR Relaxation of the Nuclei of Monoatomic Ions
AB  - The spin-lattice relaxation rates of 7Li, 23Na, 27Al, 71Ga, and 139La nuclei in
      electrolyte solutions have been investigated as functions of the isotopic
      composition of the solvent. The results show that quadrupolar relaxation of the
      nuclei of monoatomic ions is extremely sensitive to the symmetry of the solvation
      shells. The data are compared to the results for the 2H and 17O nuclei of the
      solvent molecules and the 14N nucleus of the nitrate anion. A semiquantitative
      description of the observed effects is given.

PMID- 8980058
TI  - ODESSA, a New 1D NMR Exchange Experiment for Chemically Equivalent Nuclei in
      Rotating Solids
AB  - A new 1D NMR exchange experiment in the slow-motion regime of spinning solids,
      with chemically equivalent nuclei exhibiting quadrupole coupling or chemical
      shift anisotropy, is proposed. It consists of the usual three-pulse sequence for
      2D exchange spectroscopy, P1-t1-P2-taum-P3-t-acquisition, but with the evolution
      time fixed at one-half a spinning period, t1 = TR/2, and a mixing time equal to
      an integer multiple thereof, taum = GTR. The magnetic polarizations associated
      with the various spinning sidebands are then polarized in alternate directions at
      the beginning of the mixing time. Dynamic processes during taum redistribute the
      polarizations, resulting in modified sideband patterns during the detection time,
      t. Experimental results are presented for carbon-13 and deuterium in dimethyl
      sulfone, which undergoes molecular reorientation in the solid state. The results
      are compared with simulations which include the effect of reorientation and
      longitudinal relaxation.

PMID- 8980059
TI  - The Theory of ESR Hyperfine-Structure Narrowing as Applied to Wide-Gap
      Semimagnetic Semiconductors
AB  - The theory of ESR hyperfine-structure exchange narrowing is developed. The
      kinetic equations describing the nonequilibrium magnetization dynamics of
      hyperfine components of ESR spectra are derived by using the nonequilibrium
      statistical-operator method. Numerical solution of these general equations is
      applied to the simulation of the experimental spectra of (Cd, Mn)Te crystals with
      a Mn2+ ion content of between 0.05 and 0.5%. The hyperfine-splitting constant,
      homogeneous ESR linewidth, and mean-square value of the exchange fluctuation
      frequency are obtained from the fitting of the spectra for different
      concentrations of manganese ions. The concentration dependence of the latter
      quantity is discussed in relation to the spatial dependence of magnetic-ion
      exchange interaction and the gap value in the band structure of semimagnetic
      semiconductors.

PMID- 8980060
TI  - SIMPLTN, a Program for the Simulation of Pulse NMR Spectra
AB  - SIMPLTN, a computer program for the simulation of pulse and two-dimensional NMR,
      is described and illustrated. The program is menu-driven and is designed to run
      as much like a spectrometer as possible. This approach allows a complete density
      matrix calculation to be performed, yet still makes the program easy to use.
      SIMPLTN serves as a learning tool, and allows the design and testing of new pulse
      NMR methods. A spin system and a pulse program are defined, and then the program
      calculates an FID. The simulated data can then be transformed, inspected, and
      plotted using a variety of commercial NMR software packages. Systems of up to six
      strongly coupled spins, and almost any common liquid-state pulse program, can be
      simulated. SIMPLTN includes a batch mode in which simulations may be queued, and
      parameters may be systematically varied. This paper gives an overview of the
      program, some of the unique theoretical features of the program, and examples of
      its use.

PMID- 8980061
TI  - Measurement of Dipolar Interaction of Quadrupolar Nuclei in Solution Using
      Multiple-Quantum NMR Spectroscopy
AB  - Relaxation resulting from the modulation of dipolar interaction is commonly used
      for estimating distances in molecules in solutions. However, for most nuclei with
      spin I > &frac12; the single-quantum-transition relaxation by dipolar interaction
      is masked by quadrupolar relaxation. In the present study, it is shown that even
      in systems where single-quantum relaxation times are dominated by quadrupolar
      interaction, dipolar relaxation can be measured by following the -m
      $?leftrightarrow$ m transitions. This is demonstrated for 7Li in the complex [Li
      Kryptofix 211]+X- (X = Cl, Br) dissolved in glycerol at temperatures for which
      slow motion prevails and no 1H-7Li NOE can be observed. The relaxation times that
      are most important for the assessment of the dipolar interaction of 7Li are 
      &frac12; $?leftrightarrow$ &frac12; and -${{3}?over{2}}$ $?leftrightarrow$
      ${{3}?over{2}}$ and they are measured by multiple-quantum-filtration techniques.
      For estimating the quadrupolar interaction, the relaxation times of the
      populations and those of the transitions &plusmn;&frac12; $?leftrightarrow$
      &plusmn;${{3}?over{2}}$ were measured. The longitudinal and transverse relaxation
      times of 6Li as well as the 1H-6Li NOE were also measured and, together with the
      7Li measurements, were used to obtain the strengths of dipolar (D) and
      quadrupolar (chi) interactions. The experimental data were analyzed using several
      models to describe the motion. The model that gave the best fit and resulted in
      parameters that were physically meaningful encompassed a whole-body isotropic
      motion as well as internal anisotropic motion. For this particular model, the
      following values for the quadrupolar and the dipolar interactions strength were
      obtained: D(7Li)/2pi = 6.8 kHz, chi(7Li)/2pi = 85 kHz and D(6Li)/2pi = 1.4 kHz,
      chi(6Li)/2pi = 2.6 kHz. From the value of D, an estimate of the average lithium
      proton distance was calculated to be 3.3 &Aring;, which is in fair agreement with
      crystallographic studies. The sizes of the quadrupolar and dipolar interactions
      were independently confirmed by the 7Li NMR powder spectra of the complexes that
      were used for the solution studies.

PMID- 8980062
TI  - Hahn Spin Echoes in Large Static Gradients Following a Series of 90&deg; Pulses
AB  - The intensities of the Hahn spin echoes produced by a series of 90&deg; pulses
      applied to a sample in large static field gradients are calculated. Static
      gradients are important because they can be very much larger than pulsed field
      gradients and echoes can be collected without recovery time problems. One
      application is for imaging using the stray field of a magnet (STRAFI). The high
      strength of the gradients in the stray field allows the imaging of solids and
      other systems with very broad lines. In an imaging pulse sequence consisting of
      pulses with phases 90(&deg;)x-(90(&deg;)y)n, the echoes (calculated in the
      absence of spin relaxation) have relative intensities of
      1:${{3}?over{2}}$:${{3}?over{2}}$:1(1/8):1(1/8), etc., whereas a 90(&deg;)x
      (90(&deg;)x)n pulse sequence produces echoes which have relative intensities of
      1:&frac12;:-&frac12;:-(3/8):(3/8), etc. A simple way of calculating these
      intensities is presented, using an irreducible tensor approach that has been
      termed the superspin formalism. These numbers are for infinitely short pulses on
      resonance and without relaxation or diffusion, but the extension to real systems
      is also discussed. In particular, it is shown that the attenuation down the echo
      train is due to a varying contribution from both T1 and T2 processes, as well as
      diffusion. With long T1's and slow diffusion, the decay of the echoes
      approximates T2.

PMID- 8980063
TI  - Line Narrowing in Solid-State Proton NMR with Acquisition Delay
AB  - Organic solids have extensive proton-proton dipolar interactions, and their 1H
      NMR linewidths are very large even with magic-angle spinning at moderate speeds.
      Recently it has been shown that substantial narrowing of the proton linewidths of
      organic solids can be achieved by using single-pulse excitation with acquisition
      delay or spin echo [S. Ding and C. A. McDowell, J. Magn. Reson. A 111, 212
      (1994); 115, 141 (1995); 117, 171 (1995)]. This interesting line-narrowing
      phenomenon has been further examined through the study of several amino acids,
      their deuterated analogs, and some aromatic compounds. The results confirm that
      narrow proton peaks are observed with long acquisition delay, and the peaks
      appear in the appropriate chemical-shift ranges for organic protons (0-10 ppm
      with respect to tetramethylsilane). However, except for some special cases, the
      observed peaks cannot be assigned to individual types of protons based on
      chemical-shift considerations only. To explore the reason for the line narrowing,
      the effect of acquisition delay on the 19F linewidth of CaF2 was also studied and
      compared with that on the 1H linewidths of organic solids. It is suggested that
      the broad proton peak in an organic solid is a superposition of numerous
      transitions. These transitions have different linewidths, and the narrow peaks in
      the spectrum remain observable with long acquisition delays.

PMID- 8980064
TI  - New PFG NMR Spectrometer with a Rotatable Quadrupole Coil for the Measurement of
      an Anisotropic Self-Diffusion Coefficient Tensor
AB  - A new pulsed-field-gradient spin-echo NMR spectrometer is reported which is
      specially designed for the measurement of slow and anisotropic self-diffusion by
      providing an intense and homogeneous field gradient of 12 T m-1 by a quadrupole
      coil and a high-quality current stabilizer, and also providing a mechanism by
      which both the sample cell and the quadrupole coil are rotated from the axis of
      the external field. Diffusion anisotropy is measured by a combination of coil
      rotation and magic-angle orientation of the sample. The theoretical basis for the
      method of measuring diffusion anisotropy, instrumentation details, and several
      sets of test data are given. The experimental results are reported for the
      rotation pattern of the diffusion coefficient of a smectic Ad liquid crystal of 4
      octyloxy-N-(4-cyanobenzylidene)aniline. The component parallel to the layer
      normal is shown to be 2.1 times larger than the component within the layer.

PMID- 8980065
TI  - An Efficient Method for Calculating Powder Patterns
AB  - A novel approach to the calculation of powder lineshapes is presented. Lineshapes
      from asymmetric second-rank tensor interactions are produced by summing
      lineshapes from symmetric tensors. This approach significantly reduces the
      calculation time, greatly facilitating iterative nonlinear least-squares fitting
      of experimental spectra. Results are reported for anisotropic 13C NMR lineshapes
      of glycine, benzoic acid, and octanoic acid in a urea inclusion compound.
      Lineshapes from nonuniform distributions of crystallite orientations can also be
      calculated by using distributions of the Euler angles that define the orientation
      of the principal-axis system of the chemical-shielding tensor with respect to the
      magnetic field.

PMID- 8980066
TI  - High-Resolution NMR Probe for Experiments at High Pressures
AB  - A 300 MHz high-resolution, high-pressure NMR probe which operates in the pressure
      range of 1 bar to 9 kbar at temperatures of -30 to 100&deg;C is described.
      Specialized novel design features of the probe are discussed and test spectra
      showing resolution better than 1 Hz (<3.0 x 10(-9)) for 8 mm samples are
      presented. Potential biochemical applications of this probe are illustrated by
      experiments dealing with the pressure-induced unfolding of hen egg white
      lysozyme.

PMID- 8980067
TI  - Curious Consequences of Strong Coupling in NMR Experiments Involving Selective
      Pulses
AB  - This study is concerned with the effects of applying selective pulses to systems
      with strong second-order scalar couplings in isotropic phase, where different
      transitions (rs) are associated with different transition matrix elements F+(rs).
      Two unusual features can be distinguished: the nutation angle ("flip angle")
      depends on the matrix element of the irradiated transition (rs), and, in contrast
      to the behavior of an isolated spin-(1/2) system, the norm of the three single
      transition operators [I(rs)x, I(rs)y, I(rs)z] associated with the fictitious spin
      (1/2) space of the irradiated transition (rs) is generally not conserved. It is
      necessary to consider the single-transition operators [I(rp)x, I(rp)y, I(rp)z]
      and [I(sq)x, I(sq)y, I(sq)z] associated with all connected transitions (rp) and
      (sq) that share a common energy level r or s with the irradiated transition (rs).
      If the pulse applied to the (rs) transition is sufficiently selective, the
      transverse components I(rp)x, I(rp)y, I(sq)x, and I(sq)y, can be neglected, since
      their expectation values remain equal to zero after application of a selective
      pulse to the (rs) transition, but the longitudinal components I(rp)z and I(sq)z
      acquire nonvanishing expectation values. When the selective pulse affects several
      transitions simultaneously, the response varies from one transition to another,
      depending on the matrix elements and the connectivities. These effects manifest
      themselves in unusual amplitudes and phases of signals excited by selective
      pulses, in particular in selective two-dimensional correlation spectra.

PMID- 8980069
TI  - Determination of Long-Range JXH Couplings Using "Excitation-Sculpting" Gradient
      Enhanced Heteronuclear Correlation Experiments

PMID- 8980068
TI  - Effect of Paramagnetic Ions on NMR Relaxation of Fluids at Solid Surfaces
AB  - Proton NMR longitudinal and transverse relaxation times of water-saturated powder
      packs have been measured. The powders were a series of synthetic calcium
      silicates with known concentrations of iron or manganese paramagnetic ions. The
      rate of water proton relaxation has been found to be linearly proportional to the
      concentration of paramagnetic ion. The constant of proportionality is used to
      determine the electron relaxation time of ions at the fluid-solid interface. A
      substantial relaxivity is found in the absence of paramagnetic ions. Thus the
      oxide surface itself is an unexpectedly good relaxer of fluid-borne nuclear
      spins. The results answer some long-standing questions connected with the NMR
      properties of fluid-saturated sedimentary rocks.

PMID- 8980070
TI  - Peak Power and Efficiency in Hyperbolic-Secant Decoupling

PMID- 8980071
TI  - Z Filtering in MQMAS NMR

PMID- 8980073
TI  - High-Resolution NMR Measurement of Molecular Self-Diffusion by Fast Multi-Spin
      Echo Diffusion Sequences

PMID- 8980072
TI  - Gradient-Selected NOESY-A Fourfold Reduction of the Measurement Time for the
      NOESY Experiment

PMID- 8980074
TI  - Fractional-Frequency Peaks in Two-Pulse 2D Experiments under Strong Radiation
      Damping

PMID- 8980075
TI  - Single-Point Ramped Imaging with T1 Enhancement (SPRITE)

PMID- 8980077
TI  - An Improved 2D Magic-Angle-Turning Pulse Sequence for the Measurement of Chemical
      Shift Anisotropy

PMID- 8980076
TI  - The Tolerance to J Mismatch and the Symmetry Properties of INADEQUATE CR

PMID- 8980078
TI  - Prismatic Metropolis: Race and Residential Segregation in the City of the Angels
AB  - Most major urban areas remain segregated by race, especially in terms of black
      segregation from whites. We replicate and extend the innovative approach
      developed by Farley and colleagues for understanding processes of racial
      residential segregation with data collected in Los Angeles. Using a large (N =
      4025) multiracial sample of adults, we examine (1) actual and perceived
      differences in economic status, (2) mutual preference for same race neighbors,
      and (3) racial prejudice and discrimination as hypotheses for the persistence of
      residential segregation. With a systematic experimental design we gauge
      respondent openness to living in areas with varying proportions of black, white,
      Latino, or Asian neighbors. We find no support for actual or perceived cost of
      housing as a barrier to integration. Although all groups exhibit some degree of
      ethnocentric preference for same race neighbors, this tendency is strongest among
      whites rather than blacks and plays only a small role in perpetuating
      segregation. Blacks face the greatest hostility in the search for housing and are
      consensually recognized as most likely to face discrimination in the housing
      market. Racial minorities are more open to sharing residential space with whites
      than with other minorities. We find generally higher rates of openness to
      integration than Farley and colleagues found in their recent Detroit survey.

PMID- 8980079
TI  - Race Composition and Earnings: Effects by Race, Region, and Gender
AB  - For more than 40 years, studies have reported that the higher the proportion of
      blacks in a community, the more white men earn, but the less black men earn.
      Researchers have speculated that black men earned less because earnings
      discrimination increases with percent black. Others have suggested that the
      negative effect of black representation on black men's earnings reflects black
      men's limited occupational opportunities. This study (1) investigates whether pay
      discrimination and regional location condition the relationship between black
      representation and workers' earnings and (2) examines the relationship between
      black representation and earnings for women. The results, based on 1980 Census
      data for black and white workers from 267 SMSAs, show that black representation
      was associated with higher earnings for white men and lower earnings for black
      men in both the north and south, and that part of the effect for southern black
      men stemmed from earnings discrimination. Southern black men's earnings gains
      from black representation offset some of the effects of discrimination, while
      northern black men encountered costs of black representation even in the absence
      of earnings discrimination. These findings reflect the disparate economic
      opportunities of black men in each region as manufacturing jobs have disappeared
      from the north and relocated to the south. For women, black representation led to
      higher earnings for blacks and whites. I argue that black representation does not
      lower black women's earnings because occupational sex segregation prevents black
      women from threatening white men's economic status.

PMID- 8980080
TI  - Detecting Discrimination: Analyzing Racial Disparities in Public Contracting
AB  - In City of Richmond v. J. A. Croson Co. (1989), the Supreme Court established
      strict scrutiny as the standard applicable to affirmative action programs which
      set aside quotas of public contracts for minority-owned businesses, and Aderand
      v. Pena (1995) extended the strict scrutiny standard to federal programs.
      Although the requirements of these decisions clearly require multivariate
      statistical analysis, most "disparity studies" have used a univariate comparison
      between the expected and the observed shares of contracts going to minority-owned
      firms. We examine four statistical methods-ordinary least square multiple
      regression, logit and tobit models, and a multivariate procedure for comparing
      expected and observed outcomes. Because no data are presently available at the
      level of specificity required by Croson, we constructed synthetic data sets to
      represent typical variations among large U.S. cities. Applying the statistical
      methods to each data set allows evaluation of the extent to which each method is
      able to both remove spurious and detect valid estimates of racial disparity when
      relevant control variables are added. Findings: (a) All four models removed
      apparent disparities which, although significant in univariate analysis, were
      known to be spurious. (b) Tobit and logit models, whose underlying assumptions
      better fit the nature of public contracting data, provided more accurate and more
      sensitive estimates than OLS regression. (c) Comparison of expected and observed
      outcomes within categories of control variables yielded results very similar to
      logit and tobit models and, because of the nature of the comparison specified in
      Croson, produced slightly more sensitive probability estimates.

PMID- 8980081
TI  - Wealth Accumulation across the Adult Life Course: Stability and Change in
      Sociodemographic Covariate Structures of Net Worth Data in the Survey of Income
      and Program Participation, 1984-1991
AB  - This paper reports microlevel Tobit regression analyses of sociodemographic
      covariates of the life course accumulation of total household net worth data in
      eight waves of five distinct panels-spanning over 6 years from late 1984 through
      early 1991-of the Survey of Income and Program Participation (SIPP). It is found
      that the quadratic age-wealth relationship predicted by Modigliani's Life Cycle
      Hypothesis is evident in aggregate age-median wealth profiles as well as in the
      micro data for households with positive net worth. However, when adult status
      attainment variables are entered into the regression models either by themselves
      or in combination with marital/family status variables, the age of household head
      at which net worth begins to decline is far beyond the typical retirement age. In
      addition, the traditional criterion variables of sociological status attainment
      theory-educational attainment, occupational status, and earnings-are found to be
      positively associated with household net worth, although the net effect of
      occupational status generally is not statistically significant and the earnings
      effect is nonlinear. Further, consistent with status attainment theory,
      householder minority status (black, Hispanic) is negatively associated with the
      accumulation of net worth. It is found that both single male and single female
      householder status are negatively associated with the accumulation of household
      net worth (relative to married couple households) as is the size of the household
      (measured by the number of children under age 18 present). Separate logistic
      regression analyses show that households with zero and negative net worth are
      more likely than households with positive net worth to be black and have low
      earnings. Higher levels of educational and occupational status attainment reduce
      the probability of zero net worth but not the probability of negative net worth.
      Male- and female-headed households and households headed by Hispanics also are
      more likely to have zero net worth, but not negative net worth. The estimated
      sociodemographic covariate structures of household net worth are found to exhibit
      substantial stability across both waves and panels in the SIPP-although effects
      of the 1990-1991 recession are detectable in estimates for the 1990 panel.
      Possible applications of the estimated models in demographic projections of
      household net worth are suggested.

PMID- 8980082
TI  - Congruence and Career Change in Employed Adults
AB  - Holland's theory of congruence was applied to adults changing careers. Forty-two
      nontraditional students attending college to attain a new occupation were
      surveyed. The group's average experience in the work force was 14.5 years, and
      their average age was 34.4 years. Using the C index (Brown & Gore, 1994) and Kwak
      and Pulvino's (1982) K-P index to measure congruence, data supported the
      hypothesis that employed adults in the process of changing their careers move in
      a direction of greater congruence. Further, job satisfaction was correlated
      significantly with congruence as operationalized by the C index (r = .33, p <
      .03) and the K-P index (r = .32, p < .04).

PMID- 8980083
TI  - Organizational Commitment: Clarifying the Concept and Simplifying the Existing
      Construct Typology
AB  - This paper examines popular concepts and "types" of organizational commitment in
      light of the definition of commitment and common factors that pertain to all
      commitments. It argues that a commitment is best conceptualized as a single,
      fundamental construct that may vary according to differences in focus, terms, and
      time-specific evaluation. Analysis of affective commitment measures indicates
      that certain measures contain more than one set of terms and make assumptions
      about evaluation that add constraints to the basic meaning of commitment.
      Recommendations include the argument that commitment measures address one set of
      terms and avoid evaluative phraseology.

PMID- 8980084
TI  - Affective, Continuance, and Normative Commitment to the Organization: An
      Examination of Construct Validity
AB  - Within the past few years, several studies have used the Affective, Continuance,
      and Normative Commitment Scales (Allen & Meyer, 1990; Meyer & Allen, 1984, 1991)
      to assess organizational commitment. The purpose of this paper is to review and
      evaluate the body of evidence relevant to the construct validity of these
      measures. Although some empirical questions remain at issue, the overall results
      strongly support the continued use of the scales in substantive research.

PMID- 8980085
TI  - Efficacy Expectations and Vocational Interests as Mediators between Sex and
      Choice of Math/Science College Majors: A Longitudinal Study
AB  - A longitudinal study was conducted to test the mediational role of efficacy
      expectations in relation to sex differences in the choice of a math/science
      college major. Data on 101 students were gathered prior to their entering college
      and then again after they had declared a major 3 years later. Path analytic
      results support the importance of both math self-efficacy beliefs and vocational
      interest in mathematics in predicting entry into math/science majors and
      mediating sex differences in these decisions. Also, students who described
      themselves as more extroverted were less likely to take additional math classes
      in high school. Students with stronger artistic vocational interests chose majors
      less related to math and science. School personnel are strongly encouraged to
      develop programs that challenge the crystallization of efficacy beliefs and
      vocational interest patterns before students enter college.

PMID- 8980086
TI  - Latent Structure of the Sources of Mathematics Self-Efficacy
AB  - General social cognitive theory and its career-specific elaborations posit four
      primary sources through which self-efficacy beliefs are acquired and modified:
      personal performance accomplishments, vicarious learning, social persuasion, and
      physiological states and reactions. We present two studies exploring the
      dimensionality of these sources within the context of career-relevant mathematics
      activities. In Study 1, 295 college students completed measures of the source
      variables. Testing two- through five-factor models, we found strongest support
      for a four-factor latent structure of the efficacy sources. In Study 2, involving
      481 high school students, a five-factor model fit the data well. We also found
      evidence of a higher order factor structure in both samples. Several directions
      for further research on the sources of efficacy information are considered, along
      with implications for career and academic interventions.

PMID- 8980087
TI  - An Investigation of the Effects of Protege Gender on Responses to Mentoring
AB  - Review of the literature on mentoring at work reveals a paucity of studies
      investigating gender differences in responses to mentoring. Relations of
      mentoring status and protege gender to organizational commitment, job
      satisfaction, career progress expectations, perceived employment alternatives,
      role conflict, and role ambiguity are reported for a sample of 254 managers.
      Results indicate that having a mentor may be associated with a more positive job
      experience and the perception of more employment alternatives elsewhere.
      Implications for future research are discussed.

PMID- 8980088
TI  - Mobility Strategies and Career Outcomes: A Longitudinal Study of MBAs
AB  - This research examines the impact of work- and non-work-related mobility on
      salary, promotions, job satisfaction, and organizational commitment among 671
      male and female managers over a 7-year period. Results indicated that those with
      frequent lateral moves had significant gain in salary increases compared to those
      who did not move. In addition, frequent lateral moves had a negative impact on
      work-related attitudes, specifically overall job satisfaction and organizational
      commitment. Implications of these findings for career strategies and future
      research are discussed.

PMID- 8980108
TI  - Structural classification of CDR-H3 in antibodies.
AB  - Large varieties in the lengths and the amino acid sequences of the third
      complementarity determining region of the antibody heavy chain (CDR-H3) have made
      it difficult to establish a relationship between the sequences and the tertiary
      structures, in contrast to the other CDRs, which are classified by their
      canonical structures. A total of 55 CDR-H3 segments from well determined crystal
      structures were analyzed, and we have derived several remarkable rules, which
      could partly govern the CDR-H3 conformation dependence on the sequence. Since the
      rules are physically reasonable, they are expected to be applicable to structural
      modeling and design of antibodies.

PMID- 8980109
TI  - Amino acids of the alpha1B-adrenergic receptor involved in agonist binding:
      differences in docking catecholamines to receptor subtypes.
AB  - Site-directed mutagenesis and molecular dynamics analysis of the 3-D model of the
      alpha1B-adrenergic receptor (AR) were combined to identify the molecular
      determinants of the receptor involved in catecholamine binding. Our results
      indicate that the three conserved serines in the fifth transmembrane domain (TMD)
      of the alpha1B-AR play a distinct role in catecholamine binding versus receptor
      activation. In addition to the amino acids D125 in TMDIII and S207 in TMDV
      directly involved in ligand binding, our findings identify a large number of
      polar residues playing an important role in the activation process of the alpha1B
      AR thus providing new insights into the structure/function relationship of G
      protein-coupled receptors.

PMID- 8980110
TI  - Cloning and functional analysis of the hematopoietic cell-specific phospholipase
      C(gamma)2 promoter.
AB  - Phospholipase C(gamma)2 (PLCgamma2) is a phospholipid-converting enzyme which,
      upon receptor stimulation, is activated within membrane-bound signalling
      complexes. In contrast to the highly ubiquitous PLCgamma1, PLCgamma2 is expressed
      predominantly in B-lymphocytes. Associated with antigen-coupling receptors it is
      activated by tyrosine phosphorylation after the triggering of B-cell surface
      immunoglobulin. We have cloned and sequenced the human PLCgamma2 promoter. Primer
      extension analysis reveals the existence of a major transcriptional start site.
      The TATA-less promoter contains G+C-rich stretches with a cluster of contiguous
      SP1 consensus sites, an NF1, and an AP2 site between bp -220 to -70. A construct
      containing the region from -189 to +78 confers full promoter activity, as shown
      by fusion to a luciferase reporter gene construct. The distal part of the
      promoter between bp -662 to -293 containing an SRE, EBF and CACCC box contributed
      negatively to promoter activity in the B-cell line Raji but not in three adherent
      cell lines. In Raji cells, PLCgamma2 mRNA is expressed at low levels with a half
      life greater than 4 h. After treatment with serum, TPA, retinoic acid, or with 5
      azacytidine increased levels of PLCgamma2 mRNA were induced in B-cells.

PMID- 8980111
TI  - The reaction of Escherichia coli cytochrome bo with H2O2: evidence for the
      formation of an oxyferryl species by two distinct routes.
AB  - We have re-examined the reaction of fast oxidised cytochrome bo with H202 in a
      stopped-flow spectrophotometer. Monitoring the reaction at 582 nm allows us to
      observe the formation and decay of a spectroscopically distinct intermediate
      which accumulates transiently prior to the formation of an oxyferryl species
      previously characterised in this laboratory (Watmough, N.J., Cheesman, M.R.,
      Greenwood, C. and Thomson, A.J. (1994) Biochem. J. 300, 469-475 [1]). The
      reaction shows three distinct phases of which the fast and intermediate phases
      are bimolecular and show a marked pH dependence. Initially these results appeared
      incompatible with the report that only one equivalent of H202 is required to
      generate the oxyferryl species (Moody, A.J. and Rich, P.R. (1994) Eur. J.
      Biochem. 226, 731-737 [21]. However, these data can be reconciled by a branched
      reaction mechanism whose contributions differ according to the peroxide
      concentration used.

PMID- 8980112
TI  - Subunit a of proton ATPase F0 sector is a substrate of the FtsH protease in
      Escherichia coli.
AB  - Escherichia coli FtsH is a membrane-bound ATPase with a proteolytic activity
      against the SecY subunit of protein translocase. We now report that subunit a of
      the membrane-embedded Fo part of H+-ATPase is another substrate of FtsH. Pulse
      chase experiments showed that subunit a is unstable when it alone (without Fo
      subunits b and c) was oversynthesized and that it is stabilized in the ftsH
      mutants. Selective and ATP-dependent degradation of subunit a by purified FtsH
      protein was demonstrated in vitro. These results suggest that FtsH serves as a
      quality-control mechanism to avoid potentially harmful accumulation of free
      subunit a in the membrane.

PMID- 8980113
TI  - Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for
      both human MDR1 and MDR2/P-glycoproteins.
AB  - The human MDR1 gene encodes the multidrug transporter P-glycoprotein (Pgp).
      Although the MDR2/Pgp shares about 80% identity at the amino acid level with the
      MDR1/Pgp, the MDR2/Pgp cannot act as a multidrug transporter. We examined the
      drug sensitivity of Saccharomyces cerevisiae expressing either the human MDR1/Pgp
      or MDR2/ Pgp. The human MDR1/Pgp conferred about 4-fold resistance to
      aureobasidin A, a cyclic depsipeptide antifungal antibiotic, on the drug
      sensitive yeast strains. Interestingly the human MDR2/Pgp also conferred about
      2.5-fold resistance to aureobasidin A. The resistance to aureobasidin A conferred
      by the MDR2/Pgp as well as by the MDR1/Pgp was overcome by vinblastine,
      verapamil, and cyclosporin A, depending on their concentrations, but not by
      colchicine. Aureobasidin A probably interacts directly with Pgps, because it
      overcame multidrug resistance of human cells and inhibited azidopine
      photoaffinity labeling of MDR1/Pgp in human cell membranes. These results suggest
      the possibility that the human MDR1 and MDR2/Pgps have conserved domain(s) for
      drug recognition.

PMID- 8980114
TI  - Characterization of a uterine luminal fluid protein ULF-250 using N-terminal
      microsequencing and RT-PCR identifies a novel estrogen-regulated gene in the rat
      uterus.
AB  - We had previously identified an estrogen responsive protein ULF-250, synthesized
      and secreted by the estrous rat uterus, which is immunologically distinct from
      complement C3 and alpha2-macroglobulin. The N-terminal microsequencing of ULF-250
      followed by sequence homology analysis showed that this protein is a new member
      of a class of estrogen responsive proteins in the uterus. Polymerase chain
      reaction with a ULF-250 specific primer yielded partial sequence information of
      its message. The observed pattern of ULF-250 message in the uterus during the
      various stages of the reproductive cycle in the rat suggested a possible
      regulation of ULF-250 message by 17beta-estradiol. Upstream sequencing of ULF-250
      message and its promoter domains would provide insight into the mechanism of its
      regulation by estradiol.

PMID- 8980115
TI  - Regulatable production of mature insulin from a hepatocyte cell line: insulin
      production is up-regulated by cAMP and glucocorticoids, and down-regulated by
      insulin.
AB  - We engineered a hepatoma cell line that produces an up-regulation of insulin in
      response to cAMP, dexamethasone, and retinoic acid, and a down-regulation in
      response to insulin. We devised a regulatory secretion system by placing
      proinsulin DNA under the regulatable promoter for phosphoenolpyruvate
      carboxykinase (PEPCK). To assess the ability to regulate insulin secretion, we
      used the rat hepatoma cell line, H4IIE. The H4IIE cells secreted immunoreactive
      insulin (IRI) constantly at a level of 1-3 fmol/10(6) cells/h. IRI increased
      approximately two-fold upon stimulation with 0.5 mM cAMP and five-fold with the
      addition of the cAMP-dependent phosphodiesterase inhibitor IBMX, as compared to
      baseline IRI secretion. IRI increased 18-fold by 1-500 nM dexamethasone together
      with cAMP and IBMX. Addition of exogenous insulin to the culture medium
      significantly decreased insulin mRNA expression on Northern blot.

PMID- 8980116
TI  - 1H NMR evidence that Glu-38 interacts with the N-terminal functional domain in
      interleukin-8.
AB  - In order to assess the importance of the buried Glu-38 observed in the structure
      of interleukin-8, an analog in which Glu-38 was replaced with Ala (E38A analog)
      was investigated by 1H NMR spectroscopy and neutrophil activation. Detailed
      analysis of the NMR NOESY data showed that the solution structure of the E38A
      analog is essentially the same as that for the native protein. Also, the
      neutrophil elastase activity of the E38A analog was similar to that of the native
      protein. However, the Gln-8 and Cys-9 amide proton chemical shifts, which are
      significantly downfield-shifted in the native protein, exhibit more 'normal'
      values. This observation indicates that in the native protein, Glu-38 side-chain
      carboxylate interacts with Gln-8 and Cys-9 amide protons. Although the N-terminal
      residues are critical for function, this interaction is not essential for
      neutrophil activation.

PMID- 8980117
TI  - Efforts toward deriving the CD spectrum of a 3(10) helix in aqueous medium.
AB  - There have been two recent reports suggesting that 3(10) helices can be
      distinguished from alpha helices by circular dichroism. The differentiating
      feature is stated to be a [theta]222:[theta]208 ratio (R2) distinctly smaller
      than unity. This has been reported for a C(alpha)alpha'-disubstituted homooctamer
      [Toniolo et al. (1996), J. Am. Chem. Soc. 118, 2744-2745] and for alanine-rich
      systems of 16-21 residue length with modest fractional helicity [Millhauser
      (1995) Biochemistry 34, 3873-3877]. We report here the changes in the CD spectrum
      produced by inserting aminoisobutyric acid (Aib) residues into the helical domain
      of human pancreatic amylin. In order to examine this effect at comparable net
      fractional helicities, CD spectra were measured for each species during the
      course of a helicity titration by trifluoroethanol addition. The addition of five
      Aib residues gave results of particular interest. At low net fractional helicity,
      this Aib-rich system displays a diminished pi-->pi* (circa 208 nm) rotational
      strength versus the less Aib-rich species. However, NMR data and comparisons of
      CD difference spectra suggest that fluoroalcohol-induced extension of the short
      Aib-rich helix is in the form of an alpha helix. Given the diminished intensity
      of the minimum at 208 nm at low net helicity when 3(10) conformations should
      contribute, we urge extreme caution in using a [theta]222:[theta]208 ratio
      smaller than unity as a diagnostic for 3(10) helices.

PMID- 8980118
TI  - Paxillin association in vitro with integrin cytoplasmic domain peptides.
AB  - Short cytoplasmic domains of integrin heterodimers are crucial for transduction
      of signals generated by adhesion of cells to the extracellular matrix. Here, we
      describe the use of peptides mimicking the intracellular tails of integrin
      alpha5beta1 to assay in vitro associations with cytoskeletal proteins. Our
      results suggest that the focal adhesion protein, paxillin, may interact directly
      with the intracellular region of the integrin beta1 subunit. Paxillin is known to
      form stable complexes with several signaling molecules, including focal adhesion
      kinase. Physical interaction between paxillin and the beta1 cytoplasmic domain
      suggests a model in which paxillin may function as a key intermediary in integrin
      mediated signal transduction.

PMID- 8980119
TI  - Isolation, crystallization and X-ray analysis of the quaternary complex of Phe
      tRNA(Phe), EF-Tu, a GTP analog and kirromycin.
AB  - Kirromycin inhibits bacterial protein synthesis by acting on elongation factor Tu
      (EF-Tu). Complexes of the antibiotic, Phe-tRNA(Phe), the guanosine triphosphate
      analog GDPNP, and mesophilic (Escherichia coli), as well as thermophilic (Thermus
      thermophilus) EF-Tu were isolated. Crystallization was achieved at 4 degrees C,
      pH 6.4, using ammonium sulphate as precipitant. Crystallographic data were
      recorded at cryogenic temperature on crystals exposed to synchrotron radiation.
      Crystals of the thermophilic complex are based on a rhombohedral lattice with
      cell dimensions of 137.3 A, and angles of 54.0 degrees. Although related, these
      cell parameters are different from those found in the crystals of the recently
      solved structure of the ternary complex of Phe-tRNA(Phe), GDPNP, and Thermus
      aquaticus EF-Tu (Nissen, P., Kjeldgaard, M., Thirup, S., Polekhina, G.,
      Reshetnikova, L., Clark, B.F. and Nyborg, J. (1995) Science 270, 1464-1472 [1]),
      possibly indicating some allosteric effect caused by kirromycin. Crystals of the
      mesophilic complex belong to the cubic space P432, with cell axis of 196.26 A. In
      both cases, the crystals contain one complex per asymmetric unit.

PMID- 8980120
TI  - Activation of endogenous c-Src or a related tyrosine kinase by intracellular
      (pY)EEI peptide increases voltage-operated calcium channel currents in rabbit ear
      artery cells.
AB  - The effect of activation of endogenous c-Src tyrosine kinase by (pY)EEI peptide
      was examined on voltage-operated calcium channel (VOC) currents in arterial
      smooth muscle cells. In single rabbit ear artery cells intracellular application
      of (pY)EEI peptide increased calcium channel currents. Inactive, non
      phosphorylated YEEI peptide had no effect on currents. Peptide-A, a 21 amino acid
      inhibitor of c-Src inhibited currents and prevented the effect of (pY)EEI peptide
      on calcium channel currents. These results indicate that activation of intrinsic
      c-Src increases VOC and support a role for c-Src in the regulation of VOC in
      vascular smooth muscle cells.

PMID- 8980121
TI  - Effects of carbon dioxide/bicarbonate on induction of DNA single-strand breaks
      and formation of 8-nitroguanine, 8-oxoguanine and base-propenal mediated by
      peroxynitrite.
AB  - Carbon dioxide has been reported to react with peroxynitrite (ONOO-), a strong
      oxidant and nitrating agent, to form an ONO2CO2- adduct, altering the reactivity
      characteristic of peroxynitrite. We found that bicarbonate (0-10 mM) caused a
      dose-dependent increase of up to 6-fold in the formation of 8-nitroguanine in
      calf-thymus DNA incubated with 0.1 mM peroxynitrite, whereas it produced no
      apparent effect on 8-oxoguanine formation. In contrast, bicarbonate inhibited
      peroxynitrite-induced strand breakage in plasmid pBR322 DNA and thymine-propenal
      formation from thymidine. We conclude that C02/HCO3- reacts with peroxynitrite to
      form a potent nitrating agent, but also to inactivate hydroxyl-radical-like
      activity of peroxynitrous acid.

PMID- 8980122
TI  - Shear stress inhibits apoptosis of human endothelial cells.
AB  - Physiological levels of shear stress alter the genetic program of cultured
      endothelial cells and reduce endothelial cell turnover in vivo. To test the
      hypothesis that shear stress interferes with programmed cell death, apoptosis was
      induced in human umbilical venous endothelial cells by growth factor withdrawal
      or incubation with tumor necrosis factor alpha (TNFalpha) for 18 h. Apoptosis was
      quantified by ELISA specific for histone-associated DNA fragments and confirmed
      by demonstrating the specific pattern of internucleosomal DNA fragmentation
      detected by electrophoresis and immunohistochemical staining. The TNFalpha (300
      U/ml)-mediated increase in DNA fragmentation was completely abrogated by shear
      stress. Furthermore, shear stress dose-dependently reduced DNA fragmentation
      induced by growth factor withdrawal with maximal effect at 45 dyn/cm2. Inhibition
      of the CPP32-like proteases with Ac-DEVD-CHO (100 microM) revealed similar anti
      apoptotic effects. In contrast, CPP32-independent induction of endothelial cell
      apoptosis by C2-ceramide (50 microM) was not prevented by shear stress. Thus, we
      propose that shear stress interferes with common cell death signal transduction
      involving the CPP32-like protease family and may contribute to endothelial cell
      integrity by inhibition of apoptosis.

PMID- 8980123
TI  - A model for Batten disease protein CLN3: functional implications from homology
      and mutations.
AB  - In an attempt to understand the molecular nature of Batten disease, we have
      examined the amino acid sequence of the affected CLN3 gene product (The
      International Batten Disease Consortium (1995) Cell 82, 949-957) and the site
      specific mutations which give rise to the biological defect. Homology searches
      and molecular modeling have led to the development of a model for the folding and
      disposition of the protein, possibly within a mitochondrial membrane. High
      homology with a yeast protein of unknown function suggests a strong evolutionary
      conservation of function. We speculate that a possible role for the protein may
      be in chaperoning the folding/unfolding or assembly/ disassembly of other
      proteins, specifically subunit c of the mitochondrial ATP synthase complex.

PMID- 8980124
TI  - Non-random usage of 'degenerate' codons is related to protein three-dimensional
      structure.
AB  - We report an analysis of a novel sequence-structure database of mammalian
      proteins incorporating nucleotide sequences of the exon regions of their genes
      together with protein sequence and structural information. We find that
      synonymous codon families (i.e. coding the same residue) have non-random codon
      distribution frequencies between protein secondary structure types. Their
      structural preferences are related to the third, 'silent' nucleotide position in
      a codon. We also find that some synonymous codons show very different or even
      opposite structural preferences at the N- or C-termini of structure fragments,
      relative to those observed for their amino acid residues.

PMID- 8980125
TI  - Acetylcholine receptor subunit homomer formation requires compatibility between
      amino acid residues of the M1 and M2 transmembrane segments.
AB  - The neuronal nicotinic acetylcholine receptor (nAChR) subunits alpha3 and alpha7
      have different assembly behavior when expressed in heterologous expression
      systems: alpha3 subunits require other subunits to assemble functional nAChRs,
      whereas alpha7 subunits can produce homomeric nAChRs. A previous analysis of
      alpha7/alpha3 chimeric constructs identified a domain comprising the first
      putative membrane-spanning segment, M1, as essential to homomeric assembly. The
      present study dissected further this domain, identifying three amino acid
      residues, which are located at the most intracellular third of the M1
      transmembrane segment, as important in the assembly of homomers. Moreover,
      formation of homooligomeric complexes seems to require a compatible accommodation
      between this region and certain residues of the second transmembrane segment, M2.
      Thus, compatibility between defined domains of the M1 and M2 transmembrane
      segments appears as a determinant factor governing homomer association of nAChR
      subunits.

PMID- 8980126
TI  - Occurrence of an acyl-CoA:1-acylglycerophosphorylcholine acyltransferase in plant
      mitochondria.
AB  - In the presence of oleoyl-CoA, purified and intact mitochondria from potato tuber
      formed phosphatidylcholine from labeled lysophosphatidylcholine. The labeled
      oleoyl moiety of the acyl-CoA was also incorporated in the absence of exogenous
      lysolipids, such incorporation being largely increased by the addition of
      exogenous lysophosphatidylcholine. In the presence of various other
      lysophospholipids, no synthesis of the corresponding phospholipids was observed,
      suggesting a high specificity of the acyltransferase towards the acyl acceptor.
      This enzyme was chiefly located in the outer membrane of mitochondria. These
      results indicate that any acylglycerophosphorylcholine transferred from the
      endoplasmic reticulum to mitochondria may be acylated to phosphatidylcholine.

PMID- 8980127
TI  - Re-face stereospecificity at C4 of NAD(P) for alcohol dehydrogenase from
      Methanogenium organophilum and for (R)-2-hydroxyglutarate dehydrogenase from
      Acidaminococcus fermentans as determined by 1H-NMR spectroscopy.
AB  - The two diastereotopic protons at C4 of NAD(P)H are seen separately in 1H-NMR
      spectra. This fact was used to determine the stereospecificity at C4 of NAD(P)
      for the NADP-dependent alcohol dehydrogenase from Methanogenium organophilum and
      for the NAD-dependent (R)-2-hydroxyglutarate dehydrogenase from Acidaminococcus
      fermentans. The reduction of NADP+ with [2H6]ethanol was found to yield (4R)-[4
      2H1]NADPH and the oxidation of (4R)-[4-2H1]NADH with 2-oxoglutarate to yield
      unlabelled [4-1H]NAD+. These results indicate that both enzymes are Re-face
      stereospecific at C4 of the pyridine nucleotides.

PMID- 8980128
TI  - Tissue-specific expression of the two isoforms of the mitochondrial phosphate
      carrier in bovine tissues.
AB  - Comparison of the sequence of the human mitochondrial phosphate carrier (PiC)
      gene with cDNA clones characterised from a human heart cDNA library suggested the
      existence of two isoforms of the PiC, which were generated by alternative
      splicing of exon IIIA or exon IIIB and which differed in 13 amino acids [Dolce et
      al. (1994) J. Biol. Chem. 269, 10451]. In this work the expression of isoforms A
      and B of the PiC was investigated in different bovine tissues by Northern blot
      analysis using two probes that are specific for bovine exon IIIA and exon IIIB,
      respectively. Isoform A is highly expressed in heart and skeletal muscle. Isoform
      B is ubiquitously expressed in all tissues that were examined, although at
      different levels. The tissue-specific expression pattern of the two PiC isoforms
      is similar to that reported for the isoforms of several mitochondrial proteins
      required for energy production.

PMID- 8980129
TI  - Escherichia coli inorganic pyrophosphatase: site-directed mutagenesis of the
      metal binding sites.
AB  - Aspartic acids 65, 67, 70, 97 and 102 in the inorganic pyrophosphatase of
      Escherichia coli, identified as evolutionarily conserved residues of the active
      site, have been replaced by asparagine. Each mutation was found to decrease the
      k(app) value by approx. 2-3 orders of magnitude. At the same time, the Km values
      changed only slightly. Only minor changes take place in the pK values of the
      residues essential for both substrate binding and catalysis. All mutant variants
      have practically the same affinity to Mg2+ as the wild-type pyrophosphatase.

PMID- 8980130
TI  - VASP interaction with vinculin: a recurring theme of interactions with proline
      rich motifs.
AB  - VASP (vasodilator-stimulated phosphoprotein), a protein associated with
      microfilaments at cellular contact sites, has been identified as a ligand for
      profilin and zyxin, two proteins also involved in microfilament dynamics and
      organization at these regions. Here, we report that VASP also directly binds to
      vinculin, another component of adherens junctions. Competition experiments with a
      vinculin-derived peptide showed that a proline-rich motif, located in the hinge
      region that connects vinculin's head and tail domains, is involved in VASP
      binding. The same motif is present in zyxin but the interactions of VASP with
      vinculin and zyxin differ in detail. Hence, this motif may be recognized by VASP
      in different ways when presented in distinct cellular sites.

PMID- 8980132
TI  - The algorithm of estimation of the Km values for primers in DNA synthesis
      catalyzed by human DNA polymerase alpha.
AB  - DNA synthesis with various deoxyribo homo- and heterooligoprimers in the presence
      of complementary templates was investigated. The lengthening of d(pN)n, primers
      (n = 1-10) by a unit resulted in an increase of the primer affinity and a maximal
      rate of polymerization. The coefficient of the affinity enhancement of primers
      due to formation of one hydrogen bond between primer and template was found to be
      1.35. The dependence of the primer affinity and polymerization rate on template
      primer structure in solution was analyzed and the objective laws of the changes
      of the KM and Vmax values were revealed.

PMID- 8980131
TI  - Up-regulation of a constitutively active form of the beta2-adrenoceptor by
      sustained treatment with inverse agonists but not antagonists.
AB  - In neuroblastoma X glioma hybrid, NG1O8-15, cells transfected to stably express a
      constitutively active mutant (CAM) form of the human beta2-adrenoceptor, the beta
      adrenoceptor ligands sotalol and betaxolol functioned as inverse agonists as they
      reduced basal adenylyl cyclase activity whereas the antagonists dihydroalprenolol
      and propranolol did not. Maintained presence of the CAMbeta2-adrenoceptor inverse
      agonists but not the antagonists in the culture medium of the cells resulted in a
      substantial, concentration-dependent, up-regulation of the CAMbeta2-adrenoceptor.
      Up-regulation of the CAMbeta2-adrenoceptor by the inverse agonists was prevented
      by co-incubation of the cells with either propranolol or dihydroalprenolol.
      Neither maintained elevation of cAMP levels nor the inhibition of adenylyl
      cyclase activity altered the ability of the inverse agonist ligands to cause
      receptor up-regulation.

PMID- 8980133
TI  - Self-association of LIM-kinase 1 mediated by the interaction between an N
      terminal LIM domain and a C-terminal kinase domain.
AB  - LIM-kinase 1 (LIMK1) and 2 (LIMK2) are members of a novel class of protein
      kinases containing two LIM motifs at the N-terminus. The LIM motif is thought to
      be involved in protein-protein interactions. We report here evidence that LIMK1
      self-associates and also associates with LIMK2. In vivo and in vitro binding
      analyses using variously deleted mutants of LIMKI revealed that the self
      association of LIMK1 was caused by interaction between the N-terminal LIM domain
      and the C-terminal kinase domain. The association of LIMK1 with itself and with
      LIMK2 is important for understanding how activities and functions of LIMK family
      kinases are regulated.

PMID- 8980134
TI  - Cloning and functional expression of a novel isoform of ROMK inwardly rectifying
      ATP-dependent K+ channel, ROMK6 (Kir1.1f).
AB  - We have identified from rat kidney a novel isoform of ROMK/Kir1.1, designated
      ROMK6/Kir1.1f. ROMK6 was nearly identical to ROMK1, but possessed an 122-bp
      insertion in the 5' region. Its deduced amino acid sequence was shorter by 19
      amino acids than that of ROMK1 in the amino-terminus. Unlike other previously
      reported ROMK isoforms, ROMK6 mRNA was ubiquitously expressed in various tissues,
      including kidney, brain, heart, liver, pancreas and skeletal muscle. Xenopus
      oocytes injected with ROMK6 cRNA expressed a Ba2+-sensitive weakly inwardly
      rectifying K+ current. These results indicate that ROMK6 is a novel functional K+
      channel and might be involved in K+ secretion in various tissue.

PMID- 8980135
TI  - Vacuolating toxin from Helicobacter pylori activates cellular signaling and
      pepsinogen secretion in human gastric adenocarcinoma cells.
AB  - We investigated cellular signaling and pepsinogen secretion in the human gastric
      adenocarcinoma cell line AGS which was pretreated with the purified vacuolating
      cytotoxin from Helicobacter pylori. Results indicated that vacuolating toxin
      increased the levels of inositol phosphates, cytosolic free calcium
      concentration, adenosine 3',5'-cyclic monophosphate, and phosphorylation of 31
      kDa and 22 kDa proteins in the host cells. Moreover, pepsinogen secretion from
      AGS cells was stimulated with increasing concentrations of cytotoxin. We conclude
      that besides the H. pylori cytotoxin-induced cellular vacuoles, cytotoxin
      stimulated signaling mediators and pepsinogen release are important factors
      involved in the etiology of chronic active gastritis and peptic ulcer disease.

PMID- 8980136
TI  - A complex of the soluble interleukin-6 receptor and interleukin-6 is internalized
      via the signal transducer gp130.
AB  - In human body fluids a soluble form of the interleukin-6 receptor (sIL-6R) has
      been found which together with interleukin-6 (IL-6) acts agonistically on cells
      expressing the signal transducer gp130. The means by which the sIL-6R is removed
      from the circulation is unknown. Here, we show that a complex of 125I-labelled
      recombinant sIL-6R and IL-6 is internalized by MDCK cells stably transfected with
      gp130 and by human hepatoma cells HepG2 that endogenously express the IL-6R and
      gp130. We further show that most of the internalized sIL-6R is degraded within
      lysosomes. Our studies suggest that cells expressing gp130 are capable of
      endocytosing an IL-6/sIL-6R complex, thereby removing both from the circulation.

PMID- 8980137
TI  - Toxicity of expanded polyglutamine-domain proteins in Escherichia coli.
AB  - Five neurodegenerative diseases are caused by proteins with expanded
      polyglutamine domains. Toxicity of these proteins has been previously identified
      only in mammals, and no simple model systems are available. In this paper, we
      demonstrate in E. coli that long polyglutamine domains (59-81 residues) as GST
      fusion proteins inhibit growth while smaller glutamine (10-35 residues) or
      polyalanine (61 residues) domains have no effect. Analogously in humans,
      polyglutamine repeats less than 35-40 glutamines produce a normal phenotype,
      while expansion greater than 40 glutamines is always associated with disease.
      Expression of polyglutamine proteins in E. coli may help identify the molecular
      mechanism of pathogenesis of CAG trinucleotide repeat diseases and be a useful
      screen to identify potential therapeutic compound.

PMID- 8980138
TI  - Expression of a transactivation-deficient form of thyroid transcription factor I
      decreases the activity of co-transfected thyroglobulin and thyroperoxidase
      promoters.
AB  - Thyroid transcription factor I (TTF-1) plays a critical role in thyroid
      organogenesis and in the control of expression of several thyroid-specific genes,
      like those coding for thyroglobulin and thyroperoxidase. We have expressed the
      isolated DNA-binding homeodomain of TTF-1 in cultured thyroid cells by transient
      transfection. A specific reduction in the activity of co-transfected
      thyroglobulin and thyroperoxidase promoters was observed in the presence of the
      isolated TTF-1 homeodomain, as compared to their activity measured in the
      presence of a mutated homeodomain unable to bind DNA. The activity of the SV40
      early promoter, used as a control, was only marginally affected in these
      experiments. The transactivation-deficient form of TTF-1 described here may thus
      be used for investigating other cellular processes that are dependent on TTF-1
      transcriptional activity.

PMID- 8980139
TI  - Phosphoenzyme formation by purified, reconstituted copper ATPase of Enterococcus
      hirae.
AB  - The Enterococcus hirae CopB ATPase serves in the secretion of excess copper from
      cells and belongs to the recently discovered, new class of heavy metal transport
      ATPases. We here report the affinity purification of CopB to near homogeneity and
      its reconstitution into phospholipid vesicles. In these proteoliposomes, the
      ATPase formed an acylphosphate reaction intermediate with the gamma-phosphate of
      ATP. ATPase activity and phosphoenzyme formation were inhibited by vanadate with
      an I(50) of 0.1 mM. Our results suggest that heavy metal and non-heavy metal
      ATPases operate by the same underlying mechanism.

PMID- 8980140
TI  - The primary structure of BSP-30K, a major lipid-, gelatin-, and heparin-binding
      glycoprotein of bovine seminal plasma.
AB  - BSP-30K is a major acidic glycoprotein of bovine seminal plasma. It displays
      heparin-, gelatin-, and phospholipid-binding activities. BSP-30K binds to
      spermatozoa upon ejaculation and is thought to play a role in sperm capacitation.
      We have determined its amino acid sequence, disulfide bonds, and 0-glycosylation
      sites. BSP-30K consists of 158 amino acids arranged in a mosaic structure. BSP
      30K has a unique 48-residue N-terminal extension which includes three 7-8- amino
      acid repeats and the six O-glycosylated threonine residues. The polypeptide
      stretch 49-71 is homologous to type 'A' domains found in heparin-binding proteins
      from other mammalian species. The C-terminal portion of BSP-30K is organized in a
      tandem of 40-44-residue domains each sharing the consensus pattern of the gelatin
      binding fibronectin type II module. The mosaic structure of BSP-30K suggests that
      this glycoprotein might be a factor contributing to the different sperm
      capacitating effects exerted by heparin in different mammalian species.

PMID- 8980141
TI  - Complete amino acid sequence of the A chain of mistletoe lectin I.
AB  - The complete amino acid sequence of the A chain of mistletoe lectin I was
      determined via Edman degradation sequencing of the N-terminus and tryptic and
      endoproteinase Asp-N overlapping fragments, amino acid analysis and MALDI-MS. The
      data obtained show a great homology with the chains of ribosome-inactivating
      proteins such as ricin and abrin with 111 (abrin-a) and 103 (ricin-D) amino acid
      residues conserved, respectively. The knowledge of the primary structure of MLA
      will have a fundamental impact on elucidating the biological function of
      medically applied mistletoe lectins on a molecular basis.

PMID- 8980142
TI  - Failure to activate interleukin 1beta-converting enzyme-like proteases and to
      cleave retinoblastoma protein in drug-resistant cells.
AB  - We previously found that retinoblastoma (RB) is cleaved at the initiation of
      apoptotic execution. Here we report that when an HL-60 cell line resistant to
      cytosine arabinoside (Ara-C) was exposed to this anticancer drug, neither RB
      cleavage nor apoptosis was detected. Consistent with that, processing of
      interleukin 1beta-converting enzyme (ICE) and CPP32 (an ICE-like protease) was
      also prevented in these cells. In contrast, treatment of the HL-60-Ara-C
      resistant cells with etoposide induced all of these apoptotic events.
      Furthermore, the etoposide-induced RB cleavage was inhibited by a specific
      tetrapeptide ICE-like inhibitor. Our results demonstrate that activation of the
      RB cleavage enzyme, an ICE-like protease, is required for overcoming drug
      resistance.

PMID- 8980144
TI  - The oligomerization domain of p53: crystal structure of the trigonal form.
AB  - The structure of the oligomerization domain of the p53 tumor suppressor protein
      was determined in the trigonal crystal form, using a refined NMR structure as a
      model. A synthetic peptide comprising residues 319-360 of human p53 crystallized
      in the space group P3(1)21. There is one biologically relevant tetrameric domain
      in the crystallographic asymmetric unit. The structure was refined jointly with
      NMR data, only the third such case (the previous examples being IL-1beta
      (Shaanan, B., Gronenborn, A.M., Cohen, G.H., Gilliland, G.L., Veerapandian, B.,
      Davies, D.R. and Clore, G.M. (1992) Science 257, 961-964 [1]) and BPTI (Schiffer,
      C., Huber, R., Wuthrich, K. and Van Gunsteren, W.F. (1994) J. Mol. Biol. 241, 588
      599 [21)), to 2.5 A resolution with an R factor of 0.207. The distribution of
      tumor-derived mutations in the oligomerization region together with structural
      and biological data suggest a strategy for the design of antitumor therapeutics.

PMID- 8980143
TI  - Structural basis for the catalytic mechanism and substrate specificity of the
      ribonuclease alpha-sarcin.
AB  - alpha-Sarcin is a ribosome-inactivating protein which selectively cleaves a
      single phosphodiester bond in a universally conserved sequence of the major rRNA.
      The solution structure of a-sarcin has been determined on the basis of 1898
      distance and angular experimental constraints from NMR spectroscopy. It reveals a
      catalytic mechanism analogous to that of the T1 family of ribonucleases while its
      exquisite specificity resides in the contacts provided by its distinctive loops.

PMID- 8980145
TI  - The presence of H+ and Na+ -linked Ca2+ extruding systems in Methanobacterium
      thermoautotrophicum.
AB  - The effects of monovalent cations (Na+, K+ and choline+) and the uncoupler
      3,3',4',5-tetrachlorosalicylanilide (TCS) were tested on 45Ca2+ uptake by non
      energized cells of Methanobacterium thermoautotrophicum. 45Ca2+ uptake was
      stimulated by the addition of K+ and (less) by choline+ while Na+ slowed down and
      even reversed it, thereby mimicking the energization of cells. The uncoupler
      agent, TCS, suppressed 45Ca2+ uptake in non-energized cells in the presence or
      absence of Na+ but in cells energized in an atmosphere of CO2+H2 it exerted a
      stimulating effect. Uncoupled 45Ca2+ efflux was measured in cells pre-loaded with
      45Ca2+ by means of the divalent ionophore A23187 following its washing out by
      buffer containing serum albumin. The efflux was temperature-dependent and was
      stimulated by external 40Ca2+ and Na+. In the absence of Na+, the uncoupled
      efflux was completely inhibited by TCS, whereas in the presence of Na+, TCS was
      without any effect. The results are in agreement with the model in which the Ca2+
      influx pathway is represented by a membrane potential-driven uniport whereas Ca2+
      efflux is mediated by two transport systems - Na+/Ca2+ and H+/Ca2+ antiporters -
      whose participation in the total efflux is dependent on the energy of the
      corresponding gradients of driving ions.

PMID- 8980146
TI  - Ultraviolet B stimulates production of corticotropin releasing factor (CRF) by
      human melanocytes.
AB  - Here we show that human melanocytes express the corticotropin releasing factor
      (CRF) gene and produce CRF peptide. The CRF production and secretion is markedly
      stimulated by ultraviolet B (UVB) radiation. This is the first demonstration that
      cutaneous melanocytes respond to environmental stress (UVB) through the
      production of CRF.

PMID- 8980148
TI  - Inhibition of nucleoside diphosphate kinase activity by in vitro phosphorylation
      by protein kinase CK2. Differential phosphorylation of NDP kinases in HeLa cells
      in culture.
AB  - Although a number of nucleoside diphosphate kinases (NDPKs) have been reported to
      act as inhibitors of metastasis or as a transcription factor in mammals, it is
      not known whether these functions are linked to their enzymatic activity or how
      this protein is regulated. In this report, we show that in vitro protein kinase
      CK2 catalyzed phosphorylation of human NDPK A inhibits its enzymatic activity by
      inhibiting the first step of its ping-pong mechanism of catalysis: its
      autophosphorylation. Upon in vivo 32P labeling of HeLa cells, we observed that
      both human NDPKs, A and B, were autophosphorylated on histidine residues,
      however, only the B isoform appeared to be serine phosphorylated.

PMID- 8980147
TI  - Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and
      express a novel current.
AB  - Heteromultimer formation between Kv potassium channel subfamilies with the
      production of a novel current is reported for the first time. Protein-protein
      interactions between Kv2.1 and electrically silent Kv6.1 alpha-subunits were
      detected using two microelectrode voltage clamp and yeast two-hybrid
      measurements. Amino terminal portions of Kv6.1 were unable to form homomultimers
      but interacted specifically with amino termini of Kv2.1. Xenopus oocytes co
      injected with Kv6.1 and Kv2.1 cRNAs exhibited a novel current with decreased
      rates of deactivation, decreased sensitivity to TEA block, and a hyperpolarizing
      shift of the half maximal activation potential when compared to Kv2.1. Our
      results indicate that Kv channel subfamilies can form heteromultimeric channels
      and, for the first time, suggest a possible functional role for the Kv6
      subfamily.

PMID- 8980149
TI  - Anti-peptide antibodies sensitive to the 'active' state of the beta2-adrenergic
      receptor.
AB  - Antibodies directed against a peptide corresponding to the second loop of the
      human beta2-adrenergic receptor were induced in rabbits by immunisation with the
      free peptide in complete Freund's adjuvant. The resulting antibodies were
      affinity-purified and shown to be monospecific for the target receptor. They were
      able to stimulate the L-type Ca2+ channels in whole-cell patch-clamp experiments
      on isolated adult guinea-pig cardiomyocytes. This effect was similar to that
      obtained by the specific beta2-adrenergic agonist zinterol. The antibody effects
      could be blocked with the specific beta2-adrenergic inverse agonist ICI118,551
      but not with the neutral antagonist alprenolol. These results suggest that the
      antibodies recognise the active conformer of the beta2-adrenergic receptor.

PMID- 8980150
TI  - Autocrine and paracrine roles of polypeptide growth factors, cytokines and
      vasogenic substances in normal and tumorous pituitary function and growth: a
      review.
AB  - In addition to the classical hormones, the production of numerous polypeptide
      growth factors, cytokines, vasogenic substances and neuropeptides by pituitary
      cells has been demonstrated. Expression of the corresponding receptors on
      pituitary cells enables these factors to influence growth and function of the
      pituitary by auto- or paracrine mechanisms. Thus, in addition to the external
      endocrine control of pituitary growth and function, an intrinsic intercellular
      communication network seems to be involved in the control of pituitary
      homeostasis. The cell-to-cell communication may be of importance for the pre- and
      postnatal differentiation of the pituitary, for the regulation of the cellular
      composition of the gland (by balancing mitosis and apoptosis and controlling
      angiogenesis) and for the adaption of pituitary function to altered physiological
      conditions (i.e. stress, pregnancy and diseases). Differences in the expression
      of or the response to the above-mentioned factors in pituitary adenomas indicate
      that these substances are of importance for pituitary tumorigenesis. Disturbances
      of auto-/paracrine mechanisms may not necessarily be involved in the tumor
      initiation processes, but they may play a crucial role in tumor progression.
      After the initial transformation, the clonal expansion of the tumor cell is
      dependent on its ability to escape either from the inhibitory action of growth
      suppressing factors or to develop an autocrine mechanism that allows autonomous
      growth. In summary, therefore, this review outlines the potential role of
      polypeptide growth factors, cytokines and vasogenic peptides as auto-/paracrine
      acting substances in normal pituitary and pituitary adenomas.

PMID- 8980151
TI  - The role of nitric oxide at hypothalamic and pituitary levels to alter the
      release of pituitary hormones: an invited commentary.

PMID- 8980152
TI  - Water balance in insulin-dependent diabetes mellitus can now be studied with non
      invasive techniques: an invited commentary.

PMID- 8980153
TI  - Recognizing minorities: the 22-kD growth hormone exclusion assay (GHEA)--an
      invited commentary.

PMID- 8980154
TI  - Role of high-density lipoproteins and apolipoprotein A-I in steroid hormone
      synthesis.

PMID- 8980155
TI  - L-arginine is unlikely to exert neuroendocrine effects in humans via the
      generation of nitric oxide.
AB  - There is now considerable evidence that nitric oxide is an important
      neuroregulatory agent, but there has been very little investigation of its
      possible role in neuroendocrine mechanisms in humans. We have investigated the
      effects of two nitric oxide precursors, L-arginine and molsidomine, under basal
      conditions on the pituitary hormones growth hormone (GH), prolactin, luteinizing
      hormone, follicle-stimulating hormone, thyrotrophin, adrenocorticotrophin (ACTH)
      and vasopressin, and also on serum cortisol; we have also studied the effect of L
      arginine on circulating prolactin, ACTH and cortisol in normal human subjects
      under hypoglycaemic stress. L-Arginine stimulated both GH and prolactin release
      under basal conditions but had no effect on the other hormones studied, while the
      nitric oxide donor molsidomine showed no effect on any hormone studied. L
      Arginine potentiated the hypoglycaemia-stimulated release of ACTH but did not
      influence the rise in GH. The current studies suggest that the effects of L
      arginine on the stimulation of GH and prolactin release are unlikely to be
      mediated via the generation of nitric oxide.

PMID- 8980156
TI  - Chronic treatment with CV 205-502 restores the gonadal function in
      hyperprolactinemic males.
AB  - The aim of this study was to evaluate the effects of a chronic treatment with the
      non-ergot-derived dopamine agonist quinagolide (CV 205-502) on sexual and gonadal
      function in hyperprolactinemic males. Thirteen males with macroprolactinoma and
      one with microprolactinoma were treated with CV 205-502 at the dose of 0.15-0.6
      mg/day for 6-24 months. Baseline prolactin (PRL) was 464 +/- 75.7 microg/l. All
      the patients suffered from libido impairment, five of reduced sexual potency, six
      had infertility and in four bilateral induced galactorrhea was shown. The semen
      analysis revealed a severe oligoasthenospermia with reduced sperm count, motility
      and forward progression, with an abnormal morphology and decreased viability. A
      significant reduction of serum PRL levels (nadir PRL = 12.3 +/- 5.4 microg/l) was
      obtained during the treatment. Normalization of prolactinemia was reached in 13
      of the 14 patients after 3 months. After 1 year, a significant improvement of
      sperm parameters, in terms of increase of number (from 5600 +/- 111 to 20,564 +/-
      587 mm3), motility at 1 h (from 24.8 +/- 0.1 to 52.6 +/- 0.5%), forward
      progression (from 24 +/- 1.4 to 62.3 +/- 2.9%) and normal morphology (from 53.8
      +/- 2.5 to 62.2 +/- 2.4%), was recorded. In addition, a significant increase of
      serum follicle-stimulating hormone (from 5.3 +/- 0.6 to 7.8 +/- 0.4 U/l),
      luteinizing hormone (from 4.4 +/- 0.5 to 7.7 +/- 0.4 U/l) and testosterone (from
      3.4 +/- 0.4 to 4.7 +/- 0.2 microg/l) was recorded. A significant increase of
      luteinizing hormone (9.4 +/- 0.7 U/l) and testosterone (5.2 +/- 0.4 microg/l), as
      well as a further improvement of sperm parameters, was found after 2 years of
      therapy. Sellar computed tomography and/or magnetic resonance showed a
      considerable shrinkage (> or = 30%) of tumoral mass in 8 out of 13 patients with
      macroprolacinoma. Side effects were recorded in only one patient. In conclusion,
      the treatment with CV 205-502 normalizing PRL levels improves gonadal and sexual
      function and fertility in males with prolactinoma, providing good tolerability
      and excellent patient compliance to medical treatment. This result demonstrates
      that the impairment of gonadal function in hyperprolactinemic patients is a
      functional modification.

PMID- 8980157
TI  - Lung volumes and respiratory muscle strength in adult patients with childhood- or
      adult-onset growth hormone deficiency: effect of 12 months' growth hormone
      replacement therapy.
AB  - We have described impairment of the respiratory function in adult patients with
      childhood-onset growth hormone (GH) deficiency. The aim of the present study was
      to evaluate lung volumes and respiratory muscle strength in patients diagnosed as
      GH deficient before and after 6 and 12 months of recombinant GH treatment. Ten
      adults diagnosed as GH deficient in childhood, ten adults diagnosed as GH
      deficient in adulthood and ten healthy subjects entered the study. For each
      subject, evaluation of respiratory function followed the same standard approach,
      consisting of respiratory muscle strength assessment, record of flow-volume
      curves, measurement of static lung volumes and lung diffusing capacity. Childhood
      onset GH-deficient patients had a significant reduction of maximal inspiratory (p
      < 0.01) and maximal expiratory (p < 0.05) mouth pressures. Total lung capacity,
      vital capacity and functional residual capacity were significantly reduced
      compared to healthy subjects (p < 0.05). Conversely, residual volume and
      diffusing lung capacity did not show any significant change. No significant
      change of the ratio between the percentage forced expiratory volume in 1 s and
      the forced vital capacity was observed. The decrease of respiratory mouth
      pressures was not correlated to the decrease of lung volumes. Adult-onset GH
      deficient patients had only a significant reduction of maximal expiratory
      pressure compared to healthy subjects (p < 0.05). After 6 months of treatment no
      significant differences in any of the evaluated parameters were found. After 12
      months of treatment patients with childhood-onset GH deficiency show a
      significant improvement of lung volumes (p < 0.01) and maximal respiratory mouth
      pressures (p < 0.005), whereas adult-onset GH-deficient patients show a
      significant improvement of maximal expiratory pressure (p < 0.05). In conclusion,
      the results of this study showed that adult patients affected with childhood
      onset GH deficiency suffer from an impairment of the ventilatory function due to
      a reduction of lung volumes and a decrease of respiratory pressures probably due
      to a reduction of respiratory muscle strength. This impairment was reversed after
      12 months of treatment with recombinant GH. Conversely, adult-onset GH-deficient
      patients had only an impairment of the maximal expiratory pressure, probably due
      to respiratory muscle weakness re-established after 12 months of GH therapy.

PMID- 8980158
TI  - Effects of four years' treatment with biosynthetic human growth hormone (GH) on
      body composition in GH-deficient hypopituitary adults.
AB  - Short-term trials of growth hormone (GH) substitution in hypopituitary adults
      have shown beneficial effects on body composition. To evaluate the long-term
      effects on body composition, we followed thirteen GH-deficient adults (GH < 6
      mU/l following standard provocative tests) for 4 years of GH replacement. At
      yearly intervals, serum insulin-like growth factor I (IGF-I), body weight, body
      mass index (BMI), waist, waist-to-hip circumference ratio (WHR) and resting
      systolic (SBP) and diastolic blood pressure (DBP) were determined, and body
      composition was assessed using three independent methods: total body potassium
      (TBK), bioelectrical impedance analysis (BIA) and dual-energy X-ray
      absorptiometry (DXA). Compared to baseline, IGF-I levels increased significantly
      at 1 (p = 0.0001), 2 (p = 0.0004), 3 (p = 0.006) and 4 years (p = 0.002). Body
      weight and BMI changed minimally at 1, 2 and 3 years and increased significantly
      only at the fourth year (p = 0.012 and p = 0.0009, respectively) of GH therapy.
      Waist and WHR decreased significantly at 1, 2 and 4 years (waist: p = 0.0009, p =
      0.0004, p = 0.049; WHR: p = 0.0025, p = 0.012, p = 0.047, respectively). Neither
      resting SBP nor DBP changed significantly. Fat-free mass (FFM) derived from TBK
      and BIA increased significantly at 1 (p = 0.004; p = 0.004), 2 (p = 0.003; p =
      0.05), 3 (p = 0.005; p = 0.04) and 4 years (p = 0.02; p = 0.002). Using DXA, the
      increase in FFM was significant at 1 (p = 0.007) and 2 years (p = 0.008) but not
      at 3 and 4 years. Percentage body fat measured by TBK, BIA and DXA decreased
      significantly at 1 (p = 0.008; p = 0.003; p = 0.03), 2 (p = 0.018; p = 0.06; p =
      0.049) and 4 years (p = 0.03; p = 0.002; p = 0.04). A rise in total body water,
      calculated from BIA, was observed at 1 year (p = 0.004) and was maintained
      throughout the treatment period. These data demonstrate that 4 years of GH
      treatment in hypopituitary adults is associated with sustained improvement in
      body composition.

PMID- 8980159
TI  - Reproducibility of the growth hormone response to stimulation with growth hormone
      releasing hormone plus arginine during lifespan.
AB  - The reliability and reproducibility of provocative stimuli of growth hormone (GH)
      secretion in the diagnosis of GH deficiency are still controversial both in
      childhood and in adulthood. The combined administration of GH-releasing hormone
      (GHRH) and arginine (ARG), which likely acts via inhibition of hypothalamic
      somatostatin release, is one of the most potent stimuli known so far and has been
      proposed recently as the best test to explore the maximal somatotrope capacity of
      somatotrope cells. However, it is well known that, usually, provocative stimuli
      of GH secretion suffer from poor reproducibility and that of the GHRH + ARG test
      has still to be verified. We aimed to verify the between- and within-subject
      variability of the GH response to the GHRH + ARG test in normal subjects during
      their lifespan as well as in hypopituitaric patients with GH deficiency (GHD). In
      10 normal children (C: six male and four female, age 12.3 +/- 0.9 years, body
      mass index (BMI) = 16.6 +/- 0.7 kg/m2, pubertal stages I-III), 18 normal young
      adults (Y: ten male and eight female, age 31.1 +/- 1.3 years, BMI = 21.4 +/- 0.4
      kg/m2), 12 normal elderly subjects (E: two male and ten female, age 74.4 +/- 1.8
      years, BMI= 22.6 +/- 0.6 kg/m2) and 15 panhypopituitaric GH-deficient patients
      (GHD: nine male and six female, age 40.9 +/- 4.1 years, BMI= 22.7 +/- 1.0 kg/m2),
      we studied the inter- and intra-individual variability of the GH response to GHRH
      (1 microg/kg i.v.) + ARG (0.5 g/kg i.v.) in two different sessions at least 3
      days apart. The GH responses to GHRH + ARG in C (1st vs 2nd session: 61.6 +/- 8.1
      vs 66.5 +/- 9.4 microg/l), Y (70.4 +/- 10.1 vs 76.2 10.7 microg/l) and E (57.9
      14.8 vs 52.1 +/- 8.0 microg/l) were similar and reproducible in all groups. The
      somatotrope responsiveness to GHRH + ARG also showed a limited within-subject
      variability (r = 0.71, 0.90 and 0.89 and p < 0.02, 0.0005 and 0.0005 for C, Y and
      E, respectively). Similarly in GHD, the GH response to the GHRH + ARG test showed
      a good inter- (1st vs 2nd session: 2.3 +/- 0.5 vs 2.2 +/- 0.6 microg/l) and intra
      individual reproducibility (r = 0.70, p < 0.005). The GHRH + ARG-induced GH
      responses in GHD were markedly lower (p < 0.0005) than those in age-matched
      controls and no overlap was found between GH peak responses in GHD and normal
      subjects. In normal subjects, the GH response to GHRH + ARG is very marked,
      independent of age and shows limited inter- and intra-individual variability. The
      GH response to the GHRH + ARG test is strikingly reduced in panhypopituitaric
      patients with GHD, in whom the low somatotrope responsiveness is reproducible.
      Thus, these findings strengthen the hypothesis that GHRH + ARG should be
      considered the most reliable test to evaluate the maximal secretory capacity of
      somatotrope cells and to distinguish normal subjects from GHD patients in
      adulthood.

PMID- 8980160
TI  - 22-kD growth hormone exclusion assay: a new approach to measurement of non-22-kD
      growth hormone isoforms in human blood.
AB  - Human growth hormone (GH) exists in a variety of isoforms. In the pituitary, the
      most abundant isoform is 22-kD GH (22 K GH), while other isoforms (non-22 K GH)
      are present in variable amounts. In human plasma, the GH heterogeneity
      contributes to the wide variability in GH levels measured by different
      immunoassays. The physiological role of the non-22 K GH isoforms is poorly
      understood, but they may represent a spectrum of agonists or antagonists of the
      GH receptor. It is possible that increased amounts of non-22 K GH isoforms in the
      circulation contribute to the growth failure observed in some short children and
      may be involved in the pathophysiology of acromegaly and other unrelated
      diseases. Currently, there is no method available to evaluate the ratio of non-22
      K GH isoforms to total GH in large sets of serum samples. In this report, a novel
      assay procedure is described in which monomeric and dimeric isoforms of 22 K GH
      are removed from serum and non-22 K GH isoforms are quantitated. The 22 K GH
      exclusion assay (22 K GHEA) was established as a screening method to identify
      conditions in which the ratio of non-22 K GH isoforms to total GH in human blood
      is altered. A 22 K GH-specific monoclonal antibody (MCB) is used for binding to
      22 K GH in serum. Magnetic beads coated with rat anti-mouse immunoglobulin G and
      a magnetic device are used to remove the 22K GH-MCB complexes from serum. The non
      22 K GH isoforms are measured by a polyclonal antibody-based immunoradiometric
      assay (GH-IRMA). The assay procedure was optimized systematically by statistical
      experimental designs. In serum spiked with monomeric or dimeric 22 K GH, the 22 K
      GH extraction was efficient at GH levels up to 100 microg/l (range 96.3-100%).
      The intra- and interassay precision for non-22K GH levels of 3.9 microg/l were
      2.6% and 8.7%, respectively, while for levels of 0.6 microg/l, which were very
      close to the detection limits of the assay, the coefficients were 17.0% and
      21.6%, respectively. The percentage of non-22 K GH isoforms determined in serum
      samples from three different groups of subjects showed clearly distinctive
      values. The 22 K GHEA is a new method for evaluation of non-22 K GH isoforms in
      human blood under different physiological and pathophysiological conditions.

PMID- 8980161
TI  - Developmental changes and differential regulation by testosterone and estradiol
      of growth hormone receptor expression in the rabbit.
AB  - To investigate the effects of testosterone and estradiol (E2) on growth hormone
      receptor (GH-R) gene expression, we measured GH-R mRNA levels in relation to the
      changes of sex steroid concentrations in the normal male rabbits aged 1-12 months
      and after administration of testosterone or E2 to castrated male rabbits. In the
      normal animals, E2 levels were below the detection limit in all age groups, and
      testosterone levels were below the detection limit at 1 month, increased at 2
      months and reached the plateau of the adult levels after 4 months. Liver GH-R
      mRNA levels were low at 1 month, reached a peak at 2 months and then decreased
      slightly thereafter. In the castrated animals, liver and growth plate GH-R mRNA
      levels were increased in the testosterone-treated group (162.0 +/- 12.0%, p <
      0.025; 128.4 +/- 7.6%; p < 0.025) and reduced in the E2-treated group (29.6 +/-
      6.2%, p < 0.005; 53.6 +/- 11.3%, p < 0.025). Sex steroid administration did not
      result in any significant change in GH-R mRNA levels in striated muscle, kidney
      and heart. Serum GH concentrations were increased in E2 (15.3 +/- 7.7 microg/l vs
      4.8 +/- 2.2 microg/l, p < 0.025) but the increase was not significant in
      testosterone-treated animals (8.4 +/- 7.7 microg/l vs 4.8 +/- 2.2 microg/l). Both
      testosterone and E2 treatment resulted in a reduction of mean serum growth
      hormone-binding protein (GHBP) levels compared to control animals (1077 +/- 422
      pmol/l, p < 0.01; 1137 +/- 443 pmol/l, p < 0.01; 2308 +/- 565 pmol/l). We
      conclude that in addition to their stimulatory effect on GH secretion,
      testosterone and E2 have opposite effects on GH-R gene expression in liver and
      growth plate in the rabbit. The modulation of GH-R expression by sex steroids may
      be important for growth during sexual maturation in mammals.

PMID- 8980162
TI  - Follow-up of bone mineral density in 27 cases of anorexia nervosa.
AB  - Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of
      anorexia nervosa (AN). As there is some debate about the reversibility of this
      condition, we performed a longitudinal follow-up study of 27 cases in which
      clinical, biological, X-ray and lumbar and femoral neck dual photon
      absorptiometry examinations were conducted every 6 months for up to 30 months.
      Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total
      follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192
      months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3,
      remitting AN with normalization of the gonadic function (N = 2, total follow-up
      36 months). Results were adjusted for each patient to a 6-month variation.
      Semestrial variations in lumbar bone mineral density (BMD) were -2.1 +/- 1.3%,
      +2.8 +/- 1.5%, and -0.3 +/- 1.3% (mean +/- SEM), respectively for G1, G2 and G3;
      those for femoral neck BMD semestrial variations were -5.9 +/- 2.1%, -3.8 +/-
      1.2% and -1.0 +/- 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly
      correlated positively with bone-forming markers (serum osteocalcin, alkaline
      phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased
      lumbar BMD by +1.4 +/- 2.3% every 6 months but did not stabilize femoral neck BMD
      (-3.5 +/- 1.4%). Fluoride increased lumbar BMD by 4.8 +/- 1.8%. Both lumbar and
      femoral neck BMD were stabilized in the remission group (-0.3 +/- 1.3% and -1.0
      +/- 0.6%), despite half of the follow-up time with amenorrhea. In conclusion,
      untreated AN is associated with a marked trabecular and cortical bone loss (4-10%
      per year), which can lead to osteoporotic fractures. In prevention of bone loss,
      the efficacy of estrogen is difficult to investigate in AN, even with a well
      controlled trial. Our study could provide argument that, when the observance of
      this preventive treatment is assessed, lumbar BMD can be stabilized in chronic
      forms of AN.

PMID- 8980163
TI  - Increased cardiovascular response to caffeine in perimenopausal women before and
      during estrogen therapy.
AB  - Perimenopause and menopause may be associated with an increased risk of
      cardiovascular disease, so we have investigated the cardiovascular and
      catecholamine response to caffeine in perimenopausal women compared to young
      cycling premenopausal subjects. Caffeine (250 mg per os) was administered to nine
      perimenopausal women and nine premenopausal women. The perimenopausal women
      repeated the test after 4 months of percutaneous estrogen replacement therapy.
      Systolic and diastolic blood pressure, pulse rate, plasma norepinephrine,
      epinephrine, glucose, insulin and free fatty acids were determined at 0, 15, 30,
      45, 60, 90 and 120 min after caffeine administration. No differences were found
      in the basal values of systolic blood pressure, diastolic blood pressure, pulse
      rate, norepinephrine, epinephrine, insulin, glucose and free fatty acids between
      perimenopausal women, both before and after therapy, and premenopausal women.
      Caffeine induced a higher increase of systolic (F = 4.9; p < 0.05) and diastolic
      blood pressure (F = 4.7; p < 0.05) in perimenopausal women before and during
      estrogen therapy as compared with premenopausal women. Pulse rate increased
      significantly only in perimenopausal women before therapy (F = 6.5; p < 0.03).
      These data show that perimenopause either before or during short-term estrogen
      therapy is associated with enhanced cardiovascular reactivity to caffeine. This
      phenomenon is not due to increased adrenergic and metabolic responses.

PMID- 8980165
TI  - Water distribution in insulin-dependent diabetes mellitus in various states of
      metabolic control.
AB  - Alterations in water compartments have been described in insulin-dependent
      diabetes mellitus (IDDM). Both insulin and lack of natriuretic counteracting
      response lead to water expansion, while hyperglycemica-induced osmotic diuresis
      leads to water depletion. Both total body water and water distribution in the
      extra-intracellular space, as well as their relationships to metabolic control,
      were investigated in 15 controls (30.1 +/- 1.4 years) and in 26 IDDM patients
      (31.3 +/- 1.6, diabetes duration 11.3 +/- 1.4 years) who were neither
      hypertensive nor proteinuric. The amounts of total body water (TBW) and
      extracellular water (ECW) were predicted by impedance measurements at 100 KHz and
      at 1 KHz. The amount of intracellular water (ICW) was computed as the difference
      between the two. Water distribution was estimated by measuring the ratio between
      low- and high-frequency impedance and by computing the ratio between ECW and ICW.
      The IDDM patients were divided into four groups on the basis of reference HbA(lc)
      mean and SD: A < or = mean + 2 SD < B < or = mean + 4 SD < C < or = mean +6SD <
      D. The groups were comparable with sodium intake, insulin dosage, fasting
      glycemia and laboratory hydration markers. As compared to controls, impedance
      values at 1, 5, 10, 50 and 100KHz were significantly lower in diabetic patients
      and the difference within group D increased as the frequency increased: -3.9% at
      1 KHz, -10.1% at 100 KHz. As compared to controls, groups A, B and C showed
      higher TBW, ECW and ICW while water distribution was normal, and group D showed
      higher TBW and ICW but normal ECW and a different water distribution. In all IDDM
      patients, HbA(lc) correlated with ECW (r = -0.49) and distribution ratios (r =
      0.42, impedance; r = 0.40, ECW/ICW ratio). These observations suggest that good
      or moderate long-term control IDDM patients have proportionately normal
      distributions of ECW and ICW excess. However, water excess in poor control IDDM
      patients was only found in the ICW space.

PMID- 8980164
TI  - Spironolactone therapy in hypertrichosis.
AB  - Although regarded as a benign condition, simple hypertrichosis may be very
      disturbing to a child cosmetically. An abnormality in androgen metabolism has
      been implied in the etiology of simple hypertrichosis recently. This study was
      undertaken to investigate the effect of spironolactone therapy for its
      antiandrogenic property in 12 prepubertal girls with hypertrichosis with no
      underlying etiology. The girls, with a mean age of 6.9 (1.2) years, had normal
      height and bone age. Basal hormone levels and adrenocorticotropin stimulation
      test results were in the normal ranges. Pelvic and adrenal ultrasound did not
      reveal pathology. Total and medullary hair width were measured from hair taken
      from preauricular, anterior midthigh, distal and proximal forearm areas.
      Spironolactone was started at an oral dose of 25 and increased to 100 mg x m(-2)
      x day(-1) twice daily for 1 year. Total hair width decreased significantly in the
      preauricular and anterior midthigh regions up to 6-9 months of treatment.
      Medullary hair width, which was affected by therapy to a greater extent,
      decreased significantly in all regions up to 6 months. Both total and medullary
      hair width showed a tendency to increase afterwards. No side effects were
      encountered. Spironolactone may be used in the treatment of simple
      hypertrichosis; however, more data are needed to clarify the efficacy and safety
      of anti-androgen therapy in hypertrichosis.

PMID- 8980166
TI  - Regulation of obese mRNA expression by hormonal factors in primary cultures of
      rat adipocytes.
AB  - The obese (ob) gene has been cloned recently and its protein product is called
      "leptin". Leptin is an adipocyte-derived satiety factor that regulates body
      weight homeostasis. Several hormonal factors have been reported to regulate ob
      mRNA expression. To determine which factors are most important for regulation of
      ob mRNA expression, we examined the effects of insulin, dexamethasone, a beta3
      adrenergic agonist (CGP12177A), 8-bromo-cAMP, 8-bromo-cGMP and 1-methyl-3
      isobutylxanthine (MIX) on primary cultured adipocytes. Rat adipocytes obtained
      from epididymal fat were cultured using the ceiling method. Total RNA was
      extracted and the expression of ob mRNA was measured by quantitative reverse
      transcription-polymerase chain reaction. After 24 h of incubation, 100 nmol/l
      insulin significantly increased the expression of ob mRNA (21.4-fold compared to
      control). Moreover, insulin increased ob mRNA expression in a dose-dependent
      manner over a range of 1-100 nmol/l. The effect of 100 nmol/l insulin was similar
      to that seen with 20% newborn calf serum. Dexamethasone (25-1000 nmol/l) also
      increased ob mRNA expression (2.5-2.9-fold). The effect of dexamethasone occurred
      more rapidly than insulin. CGP12177A (1-10 micromol/l) and 0.5 mmol/l 8-bromo
      cAMP had no effects, whereas 0.5 mmol/l 8-bromo-cGMP and 0.5 mmol/l MIX had
      stimulatory effects (2.8- and 2.4-fold increase in ob mRNA, respectively). The
      combination of 250 nmol/l dexamethasone and 0.5 mmol/l MIX did not have an
      additive effect on ob mRNA levels. Our present data suggest that, of these
      agents, insulin is the most important factor regulating ob mRNA expression.

PMID- 8980168
TI  - Breast-cancer screening with mammography in women aged 40-49 years. Swedish
      Cancer Society and the Swedish National Board of Health and Welfare.
AB  - For some years, there has been a perceived need for more information on the
      effect of screening for breast cancer in women aged 40 to 49. Our approach was to
      gather the most recent data on screening in this age group, to assess the
      following quantities: the likely benefit in mortality terms, measures of
      screening performance and arrest of tumour progression through screening, costs
      and public-health implications, and prospects for future screening and research.
      A collaborative meeting was held in Falun, Sweden, for which data were gathered
      in advance from all the randomized trials of breast-cancer screening that
      included women in this age group, and all identifiable substantial databases on
      service screening of women aged 40 to 49. Updated results from the Swedish
      overview of mammographic screening trials indicated relative mortality associated
      with invitation to screening of 0.77 (95% confidence interval 0.59-1.01).
      Combining all population-based randomized trials gave the relative-mortality
      figure of 0.76 (0.62-0.93), and combining all trials gave 0.85 (0.71-1.01).
      Relative-mortality figures in individual trials could be predicted by the rates
      of advanced cancers in those trials. Detailed analysis suggested faster tumour
      progression in the age group 40 to 49 compared with groups aged 50 or more. It is
      likely that mammographic screening of women aged 40 to 49 can reduce subsequent
      mortality from breast cancer, and studies on tumour progression indicate that to
      obtain substantial benefit it is probably necessary to screen every 12 to 18
      months, with 2-view mammography and double reading of films. This represents a
      greater outlay in resources and in commitment of the population. Further work
      remains to be done on the time taken for a mortality benefit to emerge, on age at
      diagnosis in some of the trials, and on costs and public-health aspects.

PMID- 8980167
TI  - Modulatory actions of progesterone on gonadotropin-releasing hormone-induced
      arachidonic acid liberation from perifused rat pituitary cells.
AB  - The stimulatory action of gonadotropin-releasing hormone (GnRH) on gonadotropin
      secretion from cultured rat pituitary cells is modulated by estradiol and
      progesterone. Recent studies provided evidence that both steroids exert effects
      on different pathways of GnRH signal transduction, which might be responsible for
      their actions on luteinizing hormone (LH) release. Here we investigated whether
      the steroids are able to modulate GnRH-induced liberation of arachidonic acid,
      which is thought to be involved in GnRH signal transduction. Pituitary cells
      obtained from female rats were treated for 48 h with vehicle, 1 nmol/l estradiol
      or 1 nmol/l estradiol + 100 nmol/l progesterone, 48 h with 1 nmol/l estradiol and
      2 h with 100 nmol/l progesterone. In addition, these cells were prelabeled with
      [3H]arachidonic acid. Then the cells were transferred to a perifusion system and
      challenged with a 6-min pulse of 100 nmol/l GnRH. Estradiol treatment enhanced
      the LH secretory response while GnRH-induced [3H]arachidonic acid liberation
      remained unaffected. However, progesterone modulated both LH secretion and
      [3H]arachidonic acid release in response to the GnRH stimulus. The short-term
      progesterone treatment paradigm enhanced the LH and arachidonic acid responses by
      up to 160 +/- 13 and 204 +/- 18%, respectively, while long-term treatment was
      inhibitory (59 +/- 9 and 63 +/- 4% vs control). Because arachidonic acid has been
      shown to be involved in GnRH signal transduction, it seems reasonable to
      speculate that the actions of progesterone described in the present study are
      related to its modulatory effect on GnRH-induced LH secretion.

PMID- 8980169
TI  - Increased mutagen-induced chromosome damage in patients with transformed
      laryngeal pre-cancerosis.
AB  - Factors that contribute to malignant transformation of laryngeal pre-neoplastic
      lesions remain largely unknown. Potential etiological factors may be related to a
      genetically controlled sensitivity to environmental carcinogens. In this study,
      we investigated bleomycin-induced chromosome damage in 15 patients who
      experienced a malignant transformation of preneoplastic laryngeal lesions during
      follow-up, as compared with chromosome fragility in 30 historical controls with
      no progression of keratoses during a 10-year follow-up, in a match-paired
      analysis. Chromosomal analysis demonstrated higher sensitivity to clastogens in
      patients with malignant progression of laryngeal pre-neoplastic lesions than that
      of control patients with no evolution of their original laryngeal keratoses (p =
      0.003). Furthermore, among the study patients, chromosome sensitivity was most
      apparent in non-tobacco users with malignant transformation of laryngeal disease.
      Our data suggest that subjects with pre-neoplastic laryngeal lesion showing
      increased susceptibility to carcinogens could be at higher risk for development
      of laryngeal carcinoma.

PMID- 8980170
TI  - Seroreactivity to HPV16 virus-like particles as a marker for cervical cancer risk
      in high-risk populations.
AB  - Sexually transmitted genital human papillomavirus (HPV) infection, most often HPV
      16, is considered the major etiologic determinant of cervical cancer. However,
      some studies have found relatively low prevalences of genital tract HPV DNA in
      some geographical areas, such as Greenland, that have high rates of cervical
      cancer. We sought to evaluate HPV 16 infection in high-risk cohorts using a
      serologic assay that assesses prior exposure as well as current infection and to
      compare the results with those obtained using a sensitive PCR-based HPV DNA
      assay. An ELISA based on HPV 16 virus-like particles was used to detect IgG serum
      antibodies in women attending sexually transmitted disease (STD) clinics in Nuuk,
      Greenland and Copenhagen, Denmark. Using a preassigned cut-off, 56% of
      Greenlandic and 41% of Danish women were seropositive (p = 0.02). In Greenlandic
      women, there was a non-significant increase in seropositivity with age, and odds
      ratios for seropositivity were similar for women with more than 5 lifetime sex
      partners. Seropositivity in the Danish women, however, increased linearly with
      increases in these 2 factors, which are likely correlates of lifetime exposure to
      genital HPVs. In contrast, any genital HPV DNA (HPV16 specifically) was detected
      in 24% and 36% of Greenlandic and Danish women, respectively and was most
      frequently detected in women below 20. The finding that HPV DNA prevalences,
      unlike seroprevalences, tended to decrease with increased lifetime risk of
      infection, provides an explanation for the lack of correlation between HPV DNA
      prevalences and cervical cancer risk in previous studies of high-risk
      populations.

PMID- 8980172
TI  - Energy, nutrient intake and prostate cancer risk: a population-based case-control
      study in Sweden.
AB  - The role of diet in the etiology of prostate cancer remains unclear, because
      results from several case-control and cohort studies on fat intake and risk of
      prostate cancer have been inconsistent; few of the studies have adjusted the
      results for caloric intake. To examine the relationship between energy, intake of
      several nutrients and risk of prostate cancer (all stages combined and advanced
      stages separately), we conducted a population-based case-control study in Orebro
      County, Sweden, from 1989 through 1994. A total of 526 patients with newly
      diagnosed prostate cancer and 536 controls, randomly selected from the population
      register and frequency-matched by age, were included in the analyses. Information
      about dietary intake was obtained from a self-administered semi-quantitative food
      frequency questionnaire. Odds ratios with 95% confidence intervals were estimated
      by unconditional logistic regression. In age-adjusted analyses, there were
      positive associations of prostate cancer (all stages combined) risk with total
      energy intake as well as intake of total fat (saturated and monounsaturated),
      protein, retinol and zinc. The positive association with energy intake was
      stronger for advanced cancer, with an excess risk of 70% for the highest quartile
      vs. the lowest. After adjustment for energy intake, there was no apparent
      association of prostate cancers (all stages combined) with any of the
      investigated nutrients. However, a weak positive association between intake of
      retinol and advanced cancer was observed. We conclude that our results provide
      some evidence that total energy intake is a risk factor for prostate cancer.

PMID- 8980171
TI  - Low frequency of apoptosis in Epstein-Barr virus-associated gastric carcinoma
      with lymphoid stroma.
AB  - In order to understand the character of Epstein-Barr virus (EBV)-associated
      gastric carcinoma with lymphoid stroma (GCLS), we examined cell proliferation and
      death in comparison with gastric carcinoma without prominent lymphoid stroma
      (conventional gastric carcinoma). The EBV-encoded small RNA I (EBER-1) and
      apoptotic cells were examined by in situ hybridization (ISH) and by terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling
      (TUNEL), respectively, on formalin-fixed paraffin-embedded surgical specimens
      from 22 GCLSs and 23 conventional gastric carcinomas. Immunostaining was
      performed for the detection of Ki-67 antigen (Ki-67), P53 protein (P53) and bcl-2
      oncoprotein (BCL-2). The percentages of apoptotic and Ki-67-positive cells were
      expressed as apoptotic indices (AI) and Ki-67 labeling indices (KI),
      respectively. EBER-1 was detected in 19 (86%) GCLSs in contrast to none in
      conventional carcinomas. Mean AI was 1.8 +/- 0.6 in the EBER-1-positive GCLSs and
      3.3 +/- 1.7 in the conventional gastric carcinomas, the value being significantly
      lower in the former (p < 0.01). Mean KI was 40.0 +/- 10.8 in the GCLSs and 48.5
      +/- 9.1 in the conventional gastric carcinomas, the value being significantly
      lower in the former (p < 0.05). P53 expression showed no significant difference
      between the 2 categories of carcinoma.

PMID- 8980173
TI  - Refining a proximal breakpoint cluster at chromosome 3p11.2 in non-papillary
      renal cell carcinomas.
AB  - Our previous cytogenetic and microsatellite analyses showed a terminal deletion
      of chromosome 3p segments with a breakpoint region between 3p11.2 and 3p14.1
      bands in 98% of non-papillary renal cell carcinomas (RCC). This breakpoint region
      covers approx. 20-25 cM genetic distance. Earlier, we found a higher frequency of
      rearrangements at chromosome 3p11.2 and have therefore now analyzed 74 sporadic
      and 26 VHL-associated RCCs with 6 polymorphic microsatellite markers mapped to
      this region. Thirty-three per cent of the breakpoints were mapped to a genetic
      distance of less than one-twentieth of the large breakpoint region 3p11.2-14.1.
      We suggest that unstable DNA sequences at chromosome 3p11.2 serve as a genetic
      basis for deletions and homologous and non-homologous recombinations to remove
      distal 3p sequences with one copy of RCC gene(s) in different types of tumors. We
      have identified a YAC clone 909d5 that spans the most frequently occurring breaks
      between loci D3S1251, D3S1101, and D3S1552 and allows this region to be cloned.

PMID- 8980174
TI  - Over-expression of bcl-xL gene in human gastric adenomas and carcinomas.
AB  - The present study was designed to clarify whether bcl-xL is involved in the
      development of carcinoma in the stomach. Levels of bcl-xL and bcl-2 mRNA were
      determined by a reverse-transcription/polymerase-chain reaction in endoscopic
      gastric biopsy specimens from 10 control subjects, 11 patients with adenomas and
      14 patients with carcinomas. In 6 of 11 adenomas, 5 of 8 early carcinomas and 3
      of 6 advanced carcinomas, the bcl-xL gene was over-expressed. In carcinomas, over
      expression of the bcl-xL gene was observed in 6 of 9 intestinal-type carcinomas
      and 2 of 5 diffuse-type carcinomas. No correlation was observed between bcl-xL
      and bcl-2 gene expression. In cases in which the bcl-xL gene was over-expressed,
      an apparent increase in the protein level of Bcl-xL was observed by immunoblot
      analysis and intense Bcl-x immunoreactivity was detected immunohistochemically
      within the tumor cells. In conclusion, we showed that bcl-xL is over-expressed in
      gastric carcinomas at both the RNA and protein levels, suggesting that over
      expression of bcl-xL may play a role in gastric carcinogenesis.

PMID- 8980175
TI  - Analysis of IgG reactivity against Human Papillomavirus type-16 E7 in patients
      with cervical intraepithelial neoplasia indicates an association with clearance
      of viral infection: results of a prospective study.
AB  - IgG reactivity against the immunodominant region aa6-35 of Human Papillomavirus
      (HPV) type-16 E7 was determined in a peptide-based ELISA in a cohort study of
      women with initial mild to moderate cervical dyskaryosis. On the basis of HPV DNA
      patterns, as determined by PCR in cervical smears prior to IgG testing, HPV-16
      positive patients were grouped as having either a cleared, a fluctuating, or a
      persistent HPV-16 infection. In a cross-sectional study at the start of
      serological follow-up, positive IgG reactivities were found more often in the
      total group of HPV-16-positive patients (20.0%) than in patients consistently
      typed as HPV-negative over a period of at least 12 months prior to testing (3.1%,
      p < 0.04). The highest proportion of positive responders was found in patients
      with a cleared HPV-16 infection (29.4%). Also, IgG reactivities found in HPV-16
      clearance patients were significantly higher than in patients with a persistent
      infection (p < 0.008). In a subsequent longitudinal study over a period of up to
      27 months, consistently positive reactivities were observed in patients with
      cleared viral infections who showed seroreactivity in the cross-sectional study,
      while mostly negative reactivities were found in patients with viral persistence.
      HPV-16 E7-specific IgG subclass responses were determined in a selection of 19
      CIN and 11 HPV-16-positive cervical carcinoma (CeCa) patients with positive E7
      specific IgG responses. IgG2 was predominant in the CIN patients, suggesting the
      presence of IFNgamma (Th1) at the site of HPV infection. In the CeCa patients
      IgG1 and IgG2 were produced equally, possibly indicating a rise in Th2 cytokines.
      Our data suggest that HPV-16 E7 IgG reactivity in a subset of CIN patients with
      viral clearance may result from successful Th1 responses.

PMID- 8980176
TI  - Molecular detection of circulating solid carcinoma cells in the peripheral blood:
      the concept of early systemic disease.
AB  - Detection of the mRNA of selected genes by reverse transcriptase-polymerase chain
      reaction (RT-PCR) is a sensitive and powerful tool for detecting cancer cells in
      bone-marrow or peripheral-blood samples. In this study, we determined whether
      carcinoembryonic antigen (CEA) mRNA is detectable in the peripheral blood of
      patients with gastrointestinal or breast cancer. In addition, we studied selected
      patients undergoing surgical procedures to assess whether tumor manipulation
      during operation enhances cancer-cell dissemination. Peripheral blood from 55
      patients with gastrointestinal or breast cancer and from 22 control cases was
      analysed for CEA mRNA using RT-PCR. For 15 selected cases undergoing curative
      surgery for cancer, samples were also obtained during and after surgery. The
      lower limit of detection was 1 to 10 CEA-positive cells diluted among 1 x 10(7)
      blood mononuclear cells. The test was positive for 20 of the 55 patients with
      cancer (36%). None of the 22 control samples were positive. An increase in
      positivity was observed with increasing stage of disease; however, even some
      patients with early-stage cancer showed positive results. In addition, CEA mRNA
      could be detected in the peripheral blood during operation in 3 of 13 patients
      whose pre-operative CEA mRNA in the peripheral blood had been negative. These
      findings suggest that, (1) RT-PCR amplification of CEA mRNA is an efficient means
      of detecting circulating solid cancer cells in the peripheral blood, although
      long-term clinical studies should be done to evaluate its usefulness; (2) not
      only breast cancer but also gastrointestinal cancer might be better regarded as a
      systemic disease even in early stages of carcinoma; and (3) surgical manipulation
      can provoke cancer-cell dissemination.

PMID- 8980177
TI  - Leisure and occupational physical activity and risk of colorectal adenomatous
      polyps.
AB  - Multiple studies have shown a protective effect for physical activity on the
      incidence of colorectal cancer, but few have addressed its association with
      incident adenomas and none have investigated its association with metachronous
      adenomas. We interviewed 2,001 patients undergoing colonoscopy in 3 New York City
      practices between 1986-1988. Of these, 298 had a first diagnosis of adenomas, 506
      had normal colonoscopies, 197 had metachronous adenomas and 345 had normal
      colonoscopies with a past history of adenomas. Subjects were queried regarding
      use of moderate amounts of recreational exercise (swimming, jogging, biking,
      racket sports and other sports) on a regular basis, and were also asked to
      estimate their level of physical activity. Occupational physical activity was
      assessed through a blinded coding of occupational titles. After adjusting for
      age, years of education, body mass index, total caloric intake, dietary fiber
      intake, dietary fat intake and years of cigarette smoking, protective effects of
      borderline significance were observed among males for leisure physical activity
      for metachronous and incident cases. Occupational physical activity was found to
      be significantly protective in male incident cases. Men with increased levels of
      either occupational or leisure activity showed a reduction for incident and
      metachronous cases. No effects were observed for females. Thus, in this study,
      both leisure and occupational physical activity were associated with a reduced
      risk of incident and metachronous adenomas among men but not women.

PMID- 8980178
TI  - Immunohistochemical detection of p53 in non-malignant and malignant oral lesions
      associated with snuff dipping in the Sudan and Sweden.
AB  - Immunohistochemistry was used to examine the expression of p53 in pre-malignant
      oral lesions and oral squamous-cell carcinomas (SCCs) from Swedish and Sudanese
      snuff-dippers, as well as in pre-malignant oral lesions and oral SCCs from non
      snuff-dippers from the Sudan, Sweden and Norway. Of the 14 SCCs from Sudanese
      snuff-dippers, 21% (3/14) expressed p53. Of the 14, 60 and 41 SCCs from non-snuff
      dippers from the Sudan, Sweden and Norway, 64% (9/14), 65% (39/60) and 68%
      (28/41) expressed p53, respectively. A statistically significant difference in
      expression of p53 was found in SCCs from Sudanese snuff-dippers compared to those
      from non-snuff-dippers from all/or any of the 3 countries. None of the suspected
      pre-malignant oral lesions from Sudanese snuff dippers or non-snuff-dippers
      expressed p53. Only 2 out of the 15 oral fibro-epithelial hyperplastic lesions
      from Swedish snuff-dippers expressed p53. Some of the oral epithelial dysplastic
      lesions, as well as the carcinoma in situ lesions from Norwegian non-snuff
      dippers, expressed p53, while the oral fibro-epithelial hyperplastic lesions did
      not. The low relative frequency of p53 expression found in oral SCCs from snuff
      dippers compared to those from non-snuff-dippers might suggest differences in
      mechanisms of oncogenic action induced by snuff. Alternatively, the pathogenesis
      of malignant oral lesions from snuff-dippers may follow a p53-independent
      pathway. In view of the unusually high levels of the tobacco-specific
      nitrosamines (TSNA) found in the type of snuff used in the Sudan, investigations
      of p53 mutations or oncogenes are needed.

PMID- 8980179
TI  - Kaposi's sarcoma and non-Hodgkin's lymphoma following the diagnosis of AIDS.
      Multistate AIDS/Cancer Match Study Group.
AB  - We linked records of 83,434 AIDS cases reported to AIDS registries through 1990
      to cancer registry records during times when overlap in registration existed. Of
      8,496 Kaposi's-sarcoma (KS) cases meeting enrollment criteria, 1,045 occurred
      semesters 2 through 4 (6 through 23 months) after another AIDS-defining illness.
      KS risk in this period after AIDS declined steadily over the 1980s. Adjusting for
      age, gender, ethnic origin and calendar time period, we found the relative risk
      (RR) of KS to be 106,000 for homo/bisexual men with AIDS and 13,000 for other men
      with AIDS. Risk was highest for homo/bisexual men between 30 and 39 years old and
      among 20- to 29-year-old non-homo/bisexual men. The RR in black men was
      approximately half that reported in white men among homo-bisexual men and others.
      Between the second and fourth semester after AIDS, the ratio of RR of KS to that
      of non-AIDS-related cancers increased 1.5-fold. In a similar analysis, there were
      335 non-Hodgkin's lymphoma (NHL) cases in semesters 2 through 4 after AIDS. The
      overall risk was elevated 283-fold in homo/bisexual men and the RR ratio
      increased 1.8-fold between semester 2 and 4 after AIDS. In summary, the risk of
      KS following another AIDS-defining illness is strikingly high, more in white men
      than in black men, and the risks of KS and, especially, NHL appear to increase
      with time from AIDS.

PMID- 8980180
TI  - The international classification of childhood cancer.
AB  - The International Classification of Childhood Cancer (ICCC) updates the widely
      used Birch and Marsden classification scheme. ICCC is based on the second edition
      of the International Classification of Diseases for Oncology (ICD-O-2). The
      purpose of the new classification is to accommodate important changes in
      recognition of different types of neoplasms, while preserving continuity with the
      original classification. The grouping of neoplasms into 12 main diagnostic groups
      is maintained. The major changes are: (1) intracranial and intraspinal germ-cell
      tumours now constitute a separate subgroup within germ-cell tumours; (2)
      histiocytosis X (Langerhans-cell histiocytosis) is excluded from ICCC; (3)
      Kaposi's sarcoma is a separate subgroup within soft-tissue sarcomas; (4) skin
      carcinoma is a separate subgroup within epithelial neoplasms; (5) "other
      specified" and "unspecified" neoplasms are now usually separate sub-categories
      within the main diagnostic groups. Draft copies of the ICCC were distributed to
      some 200 professionals with interest and expertise in the field and their
      comments are considered in this final version. This classification will be used
      for presentation of data in the second volume of the IARC Scientific Publication
      "International Incidence of Childhood Cancer." A computer programme for automated
      classification of childhood tumours coded according to ICD-O-1 or ICD-O-2 is now
      available from IARC.

PMID- 8980181
TI  - PCR-based high-risk HPV test in cervical cancer screening gives objective risk
      assessment of women with cytomorphologically normal cervical smears.
AB  - Cervical-cancer screening programmes using cytomorphological criteria could be
      more efficient if the screening included objective individual risk factors for
      women with normal cytology, such as a test for high-risk human papillomavirus
      (HPV). The value of a PCR-based test for high-risk HPV types was studied in a
      cohort of 1622 women presenting in a routine triannual population-based screening
      programme. Women were included in the study when they had no previous history of
      cervical dysplasia; and their initial Pap smear was read as normal (Pap 1 or 2).
      The mean age of the women was 42 years (range 34-54 years) and mean follow-up
      time was 40 months (range 5-73 months). Women were referred for colposcopically
      directed biopsies if they had had 2 successive cervical smears read as Pap 3a
      (mild to moderate dyskaryosis) or one read as > or = Pap 3b (severe dyskaryosis).
      Women with histologically confirmed cervical intraepithelial neoplasia grade III
      (CIN III) were considered positive cases. All women were tested for 14 high-risk
      HPV genotypes. Of the 86 high-risk HPV-positive women, 6 developed CIN III,
      whereas only 1 of the 1536 HPV-negative women did. The women with normal Pap
      smears containing high-risk HPV genotypes were 116 times (95% CI, 13-990) more at
      risk of developing CIN III, in contrast to women without high-risk HPV. These
      results support the view that the interval between successive smears in cervical
      cancer screening can be increased considerably for women with cytomorphologically
      normal and high-risk HPV-negative cervical smears as determined by PCR.

PMID- 8980182
TI  - Early detection of cervical cancer by visual inspection: a population-based study
      in rural India.
AB  - A total of 3784 women aged 35 and above living in 26 villages in rural
      Maharashtra state, India, were invited to undergo a pelvic examination, to
      evaluate the performance of unaided visual inspection by trained paramedical
      workers in detecting cervical cancer. Of this number, 2135 (56.4%) women complied
      with the invitation. Paramedical workers scored 1120 (57.3%) and 118 (6%) women
      as having abnormal cervices using the low- and high-threshold criteria
      respectively. There was good agreement between the visual findings of the
      paramedical workers and those of a gynaecologist. All subjects had a cervical
      smear. A total of 10 cervical cancers were detected by cytology/histology. The
      sensitivity of visual inspection by paramedical workers to detect cervical cancer
      was 90.0% using the low threshold and 60.0% with the high threshold to define a
      positive test. The values for specificity were 42.8% and 94.5% respectively. The
      results obtained by the gynaecologist were very similar. Cost savings implied by
      limiting cytology/other investigations to approximately half of the population
      pre-selected on the basis of visual inspection are likely to be offset by the
      necessity to repeat the test at frequent intervals, repeated follow-up visits and
      other investigations.

PMID- 8980183
TI  - Effects of human fibroblasts on invasiveness of oral cancer cells in vitro:
      isolation of a chemotactic factor from human fibroblasts.
AB  - Oral fibroblasts stimulated invasion of oral-carcinoma cells into the collagen
      matrix. The mechanisms of the fibroblast-induced stimulation of invasiveness was
      further investigated by examining cell motility and proteolytic activity of tumor
      cells, using mainly an adenoid-cystic-carcinoma cell line (ACCS) and normal
      fibroblasts from gingival tissues. Conditioned medium from the fibroblasts grown
      in serum-free medium was fractionated on a Superdex 200 pg column, and Peak 1
      eluted at 200 to 300 kDa and Peak 2 eluted at 50 to 100 kDa were found to contain
      different specific activity. Treatment of ACCS cells with Peak 1 resulted in an
      increase in the production of proteolytic enzymes. Peak 2 stimulated both
      chemotaxis and chemokinesis of ACCS cells. A chemotactic factor was purified from
      the heparin-unbound fraction of Peak 2 by anion exchange and hydrophobic
      chromatography, and was named "fibroblast-derived motility factor (FDMF)". At 1
      microg/ml, FDMF stimulated chemotaxis of ACCS cells by 4-fold compared with
      unstimulated controls. Characterization of the physicochemical properties of FDMF
      suggested that it might be different from any known motility factors. Exposure of
      ACCS cells to FDMF resulted in reduced amounts of actin stress fiber in the
      cytoplasm and induction of tyrosine phosphorylation of several cellular proteins
      detectable 30 to 60 min after treatment. These FDMF-induced changes were blocked
      by pre-treatment either with genistein or with pertussis toxin. These findings
      suggest that FDMF may be a novel protein which stimulates cell motility via a
      signaling pathway mediated by a pertussis-toxin-sensitive G protein and tyrosine
      phosphorylation.

PMID- 8980184
TI  - Expression of a truncated EGF receptor is associated with inhibition of
      pancreatic cancer cell growth and enhanced sensitivity to cisplatinum.
AB  - Human pancreatic cancers over-express the epidermal growth factor receptor (EGF
      R) and all 5 known ligands of the EGF family, including EGF, transforming growth
      factor-alpha (TGF-alpha), amphiregulin, betacellulin and heparin-binding EGF-like
      growth factor (HB-EGF). The aim of the present study was to confirm the presence
      of EGF-R-dependent autocrine loops in a human pancreatic cancer cell line and to
      explore the possibility that interrupting EGF-R activation by introducing a
      truncated receptor abrogates pancreatic cancer cell growth. The anchorage
      independent growth of PANC-1 human pancreatic cancer cells, previously shown to
      express TGF-alpha, was inhibited by specific anti TGF-alpha antibodies. PANC-1
      cells were then either transfected with an expression plasmid encoding a kinase
      deficient EGF-R cDNA (HER653) or infected with the same EGF-R cDNA using a
      retroviral vector. Multiple transfected and infected clones co-expressed the
      truncated EGF-R and endogenous EGF-R as revealed by Northern blot analysis and
      immunoblots. In these clones, there was a marked attenuation in EGF- and TGF
      alpha-mediated EGF-R tyrosine phosphorylation and c-fos induction. There was also
      a significant decrease in colony formation in soft agar by comparison with
      control cells and a significant increase in the effect of the growth-inhibitory
      effect of the alkylating agent cisplatinum in these clones. Our observations
      indicate that dominant negative inhibition of EGF-R may have therapeutic
      potential in pancreatic cancer.

PMID- 8980185
TI  - Change in morphological and functional cytodifferentiation induced by seminal
      vesicle mesenchyme in cell suspensions of rat Dunning prostatic adenocarcinoma
      cells.
AB  - Previous experiments have shown that seminal vesicle mesenchyme (SVM) can induce
      small 0.5 mm fragments of the rat Dunning tumor (DT) to undergo secretory
      differentiation with a concomitant reduction in tumorigenesis. In the present
      experiments Dunning tumor epithelial cells (DTE) were purified from DT cell
      suspensions by Percoll gradient centrifugation and recombined with neonatal rat
      SVM. The resultant tissue recombinants (SVM + DTE) were grafted under the renal
      capsule of male athymic mice and grown for 2 months. Under these conditions SVM
      induced the DTE to exhibit a highly differentiated secretory phenotype by forming
      ducts lined with tall columnar epithelial cells or large clear cells with pale
      cytoplasm. Undifferentiated epithelial cells of the parental DT were rarely
      observed in these tissue recombinants. The loss of tumorigenicity in SVM + DTE
      recombinants was associated with a striking reduction of epithelial 3H-thymidine
      labeling index in SVM + DTE recombinants (DT = 8.31%; SVM + DTE recombinants =
      1.10%). Differences in putative secretory proteins were also observed by SDS-PAGE
      in SVM + DTE recombinants in comparison with DT. Testosterone metabolism was
      examined in epithelial cells recovered from grafts of DT vs. SVM + DTE tissue
      recombinants by thin layer chromatography and revealed that the major metabolite
      produced by DTE was androstenedione, whereas in epithelium isolated from SVM +
      DTE tissue recombinants the major androgen metabolite was 5alpha-DHT. Thus, after
      induction by SVM the DTE metabolized androgens in a pattern similar to the normal
      rat dorsal prostate. The SVM-induced changes in DTE suggest the possibility that
      emerging or established carcinomas might be regulated at least in part by their
      connective tissue microenvironment.

PMID- 8980186
TI  - Expression of the co-stimulatory molecule CD40 on melanoma cells.
AB  - We have previously shown that one of the co-factors required for generation of T
      cell responses, B7.1, is variably expressed on melanoma cells. In the present
      studies we have examined the expression of another important co-factor in T-cell
      responses, viz., CD40, and investigated regulation of its expression and possible
      function(s). PCR analysis revealed mRNA for CD40 in all 18 cell lines established
      from metastatic melanoma and the majority of those from 6 primary melanoma. CD40
      protein was detectable in approximately 50% of the cell lines by flow cytometry
      and in sections from only 2 of 20 melanoma. Expression of CD40 protein was
      increased in 2 of 3 cell lines with constitutive CD40 expression by interferon
      gamma but not by granulocyte/macrophage colony-stimulating factor, interleukin-2
      or tumor necrosis factor-alpha. Interaction of monoclonal antibody with CD40 on
      melanoma cells resulted in an increase in their cell division but did not
      increase expression of the costimulatory factor B7. Our results suggest that CD40
      expression on melanoma may have important effects on their biology. The influence
      of CD40 expression on T-cell responses to melanoma remains to be investigated.

PMID- 8980187
TI  - Production of cell-associated PDGF-AA by a human sarcoma cell line: evidence for
      a latent autocrine effect.
AB  - The alternative splicing of platelet-derived growth factor A-chain is known to
      result in 2 different protein products. One variant is encoded by transcripts
      containing the 69 nts representing exon 6 (PDGF-AA(L)), and one variant is
      encoded by transcripts in which exon 6 is excluded (PDGF-AA(S). Transfection
      assays have suggested that the long splice variant of the A-chain is mainly
      associated with membrane- and matrix-associated heparan sulphate proteoglycans,
      whereas the shorter variant is soluble. We describe a human sarcoma cell line (U
      2197) that expresses a high level of PDGF-A transcripts. Immunoprecipitations
      revealed cell-associated protein products of mainly 24, 28 and 33 kDa and less
      abundant forms of 40-45 kDa, while no PDGF was found in the medium. Analysis of
      extracellular medium in a radioreceptor assay confirmed that PDGF was not
      secreted by the U-2197 cells. The addition to U-2197 cultures of a carboxy
      terminal peptide that specifically competes with the binding of the long splice
      variant of PDGF-AA to extracellular matrix and cell membranes resulted in the
      release of 3 PDGF-AA-specific dimeric proteins with molecular masses of 33, 37
      and 45 kDa. Furthermore, polymerase chain reaction studies discriminating between
      the long and the short splice variants of the PDGF-A transcripts revealed that U
      2197 expressed relatively higher amounts of the long splice variant compared with
      U-343 MGa Cl 2:6, which is known to secrete PDGF-AA. These cell-associated forms
      of PDGF, released to the medium by adding carboxy terminal peptide, increased the
      tyrosine kinase activity of the endogenous PDGF alpha-receptor.

PMID- 8980188
TI  - Lymphoblastoid cells transfected with c-myc: downregulation of EBV-lytic antigens
      and impaired response of autologous CD4+ T cells in vitro.
AB  - Normal EBV-positive lymphoblastoid B-cell lines (LCL) were transfected with
      vectors containing the c-myc oncogene (pHEBO-E(mu)-myc) or control vectors (pHEBO
      E(mu)) and analyzed for the expression of EBV-lytic and latent antigens. While
      EBV-latent antigens were normal in the c-myc transfectants, there was an almost
      complete downregulation of EBV-lytic antigens, including BZLF1, EA(D), gp340 and
      VCA. These observations were consistently repeated on 6 different LCLs
      transfected with c-myc. Unlike control LCLs, the c-myc transfectants did not
      release infectious EBV. PCR analysis demonstrated that BZLF1 mRNA was virtually
      absent in c-myc transfectants, possibly suggesting that the deregulated c-myc
      imposed a block in the EBV-lytic cycle at this particular level. c-myc
      transfectants failed to sustain the proliferative response of autologous CD4+ T
      cell clones with specificity for EBV-lytic antigens. However, they regained this
      capacity after incubation with ultraviolet-inactivated EBV or gp340 antigen in
      vitro, also indicating that their antigen-presenting capacities were not
      impaired. c-myc transfectants failed to elicit a secondary proliferative response
      by autologous CD4+ T cells purified from the peripheral blood of EBV-seropositive
      donors. Exposure of c-myc transfectants to UV-inactivated EBV again resulted in a
      proliferative CD4+ T-cell response comparable to that elicited by the control
      LCLs. Collectively, our data provide evidence for the remarkable ability of an
      oncogene to influence the life cycle of a virus and to modify the antigenicity of
      the infected cells.

PMID- 8980189
TI  - Over-expression of a novel member of the immunoglobulin superfamily in Min mouse
      intestinal adenomas.
AB  - Germline mutations of the APC (adenomatous polyposis coli) gene lead to multiple
      intestinal tumors in familial adenomatous polyposis patients and in Min (multiple
      intestinal neoplasia) mice. Consequently, these mice provide an excellent model
      for familial colon cancer. We have identified an Mr approx. 66 kDa glycoprotein
      which is preferentially expressed at the cell surface of cell lines established
      from chemically induced rat colon carcinomas. Cloning of the corresponding Tage4
      cDNA has revealed that this protein contains the conserved amino acids
      characteristic of members of the immunoglobulin gene superfamily. Here, we
      analyze expression of the mouse Tage4 gene in Min mouse intestinal adenomas. RT
      PCR analysis allowed us to detect expression of this gene in all the mouse
      adenomas tested. In contrast, lower levels of Tage4 mRNA were found in the
      intestinal tract and barely detectable levels in other tissues of normal mice.
      Furthermore, Tage4 mRNA was detected in a series of mouse intestinal adenomas by
      in situ hybridization. A strong signal was seen in the samples analyzed.

PMID- 8980190
TI  - The roles of Fas and perforin in LAK T-cell/bispecific antibody-mediated killing
      of the murine B-lymphoma cells, BCL1.
AB  - The aim of this study was to construct bispecific F(ab')2 [anti-CD3 x anti-BCL1
      idiotype (Id)] Abs (BsAbs) which would enable lymphokine-activated killer (LAK) T
      cells to kill Id+ mouse BCL1 lymphoma cells, and to determine the mechanism(s)
      underlying cell death. Using 4-day activated LAK T cells from either perforin
      knockout mice or FasL-deficient gld mice, we show that the Fas pathway, but not
      perforin, is required for BsAb-mediated LAK T-cell-induced killing of BCL1 cells.

PMID- 8980192
TI  - Guidelines for treating erectile dysfunction issued.

PMID- 8980191
TI  - Investigators seeking new ways to stem rising tide of resistant fungi.

PMID- 8980193
TI  - New routes to goals of prostate cancer research.

PMID- 8980194
TI  - Collaboration needed for HIV vaccine success.

PMID- 8980196
TI  - From the Centers for Disease Control and Prevention. Update: fatal air bag
      related injuries to children--United States, 1993-1996.

PMID- 8980195
TI  - From the Food and Drug Administration.

PMID- 8980197
TI  - From the Centers for Disease Control and Prevention. Update: respiratory
      syncytial virus activity--United States, 1996-97 season.

PMID- 8980198
TI  - From the Centers for Disease Control and Prevention. FDA approval of a
      haemophilus b conjugate vaccine combined by reconstitution with an acellular
      pertussis vaccine.

PMID- 8980199
TI  - Thrombolysis for stroke.

PMID- 8980200
TI  - Dose of non-heat-treated factor VIII concentrate and HIV-1 RNA levels.

PMID- 8980201
TI  - Stab wounds associated with terrorist activities in Israel.

PMID- 8980202
TI  - Stab wounds associated with terrorist activities in Israel.

PMID- 8980203
TI  - Stab wounds associated with terrorist activities in Israel.

PMID- 8980204
TI  - Changes in bone mineral density in male athletes.

PMID- 8980205
TI  - Changes in bone mineral density in male athletes.

PMID- 8980206
TI  - A randomized trial comparing aerobic exercise and resistance exercise with a
      health education program in older adults with knee osteoarthritis. The Fitness
      Arthritis and Seniors Trial (FAST).
AB  - OBJECTIVE: To determine the effects of structured exercise programs on self
      reported disability in older adults with knee osteoarthritis. SETTING AND DESIGN:
      A randomized, single-blind clinical trial lasting 18 months conducted at 2
      academic medical centers. PARTICIPANTS: A total of 439 community-dwelling adults,
      aged 60 years or older, with radiographically evident knee osteoarthritis, pain,
      and self-reported physical disability. INTERVENTIONS: An aerobic exercise
      program, a resistance exercise program, and a health education program. MAIN
      OUTCOME MEASURES: The primary outcome was self-reported disability score (range,
      1-5). The secondary outcomes were knee pain score (range, 1-6), performance
      measures of physical function, x-ray score, aerobic capacity, and knee muscle
      strength. RESULTS: A total of 365 (83%) participants completed the trial. Overall
      compliance with the exercise prescription was 68% in the aerobic training group
      and 70% in the resistance training group. Postrandomization, participants in the
      aerobic exercise group had a 10% lower adjusted mean (+/- SE) score on the
      physical disability questionnaire (1.71 +/- 0.03 vs 1.90 +/- 0.04 units; P<.001),
      a 12% lower score on the knee pain questionnaire (2.1 +/- 0.05 vs 2.4 +/- 0.05
      units; P=.001), and performed better (mean [+/- SE]) on the 6-minute walk test
      (1507 +/- 16 vs 1349 +/- 16 ft; P<.001), mean (+/-SE) time to climb and descend
      stairs (12.7 +/- 0.4 vs 13.9 +/- 0.4 seconds; P=.05), time to lift and carry 10
      pounds (9.1 +/- 0.2 vs 10.0 +/- 0.1 seconds; P<.001), and mean (+/-SE) time to
      get in and out of a car (8.7 +/- 0.3 vs 10.6 +/- 0.3 seconds; P<.001) than the
      health education group. The resistance exercise group had an 8% lower score on
      the physical disability questionnaire (1.74 +/- 0.04 vs 1.90 +/- 0.03 units;
      P=.003), 8% lower pain score (2.2 +/- 0.06 vs 2.4 +/- 0.05 units; P=.02), greater
      distance on the 6-minute walk (1406 +/- 17 vs 1349 +/- 16 ft; P=.02), faster
      times on the lifting and carrying task (9.3 +/- 0.1 vs 10.0 +/- 0.16 seconds;
      P=.001), and the car task (9.0 +/- 0.3 vs 10.6 +/- 0.3 seconds; P=.003) than the
      health education group. There were no differences in x-ray scores between either
      exercise group and the health education group. CONCLUSIONS: Older disabled
      persons with osteoarthritis of the knee had modest improvements in measures of
      disability, physical performance, and pain from participating in either an
      aerobic or a resistance exercise program. These data suggest that exercise should
      be prescribed as part of the treatment for knee osteoarthritis.

PMID- 8980207
TI  - Moderate-intensity exercise and self-rated quality of sleep in older adults. A
      randomized controlled trial.
AB  - OBJECTIVE: To determine the effects of moderate-intensity exercise training on
      self-rated (subjective) sleep quality among healthy, sedentary older adults
      reporting moderate sleep complaints. DESIGN: Randomized controlled trial of 16
      weeks' duration. SETTING: General community. PARTICIPANTS: Volunteer sample of 29
      women and 14 men (of 67 eligible subjects) aged 50 to 76 years who were
      sedentary, free of cardiovascular disease, and reported moderate sleep
      complaints. No participant was withdrawn for adverse effects. INTERVENTION:
      Randomized to 16 weeks of community-based, moderate-intensity exercise training
      or to a wait-listed control condition. Exercise consisted primarily of four 30-
      to 40-minute endurance training sessions (low-impact aerobics; brisk walking)
      prescribed per week at 60% to 75% of heart rate reserve based on peak treadmill
      exercise heart rate. MAIN OUTCOME MEASURE: Pittsburgh Sleep Quality Index (PSQI).
      RESULTS: Compared with controls (C), subjects in the exercise training condition
      (E) showed significant improvement in the PSQI global sleep score at 16 weeks
      (baseline and posttest values in mean [SD] for C=8.93 [3.1] and 8.8 [2.6];
      baseline and posttest values for E=8.7 [3.0] and 5.4 [2.8]; mean posttest
      difference between conditions=3.4; P<.001; 95% confidence interval, 1.9-5.4), as
      well as in the sleep parameters of rated sleep quality, sleep-onset latency
      (baseline and posttest values for C=26.1 [20.0] and 23.8 [15.3]; for E=28.4
      [20.2] and 14.6 [13.0]; net improvement=11.5 minutes), and sleep duration
      baseline and posttest scores for C=5.8 [1.1] and 6.0 [1.0]; for E=6.0 [1.1] and
      6.8 [1.2]; net improvement=42 minutes) assessed via PSQI and sleep diaries
      (P=.05). CONCLUSIONS: Older adults with moderate sleep complaints can improve
      self-rated sleep quality by initiating a regular moderate-intensity exercise
      program.

PMID- 8980209
TI  - History of visible rectal bleeding in a primary care population. Initial
      assessment and 10-year follow-up.
AB  - OBJECTIVE: To determine whether a complaint of visible rectal bleeding that is
      elicited by a screening review of systems merits investigation and to assess the
      accuracy of a defined protocol to evaluate bleeding. DESIGN: Prospective cohort
      study. SETTING: Primary care clinics in a veterans medical center. PATIENTS: We
      used an 8-item review of systems to identify 297 individuals with visible rectal
      bleeding; 201 (68%) of these individuals completed a specified protocol
      consisting of double-contrast barium enema (DCBE) examination, rigid
      sigmoidoscopy, and follow-up visit after 6 to 12 months. Ten years later we
      verified the diagnosis in 131 (93%) of 141 patients whose initial evaluation
      suggested no cause, or a benign anorectal cause, of bleeding. MAIN OUTCOME
      MEASURES: Final diagnoses after 2 and 10 years; sensitivity and specificity of
      symptoms, DCBE, and rigid sigmoidoscopy. RESULTS: We diagnosed serious disease in
      48 (24%) of the 201 patients; 26 had polyps, 9 had inflammatory bowel disease,
      and 13 (6.5%) had colon cancer. Symptoms did not predict the diagnosis. Neither
      DCBE nor rigid sigmoidoscopy alone was sufficiently sensitive to be used alone,
      but the combination of DCBE and rigid sigmoidoscopy had a sensitivity of 0.96 and
      a specificity of 0.76 for the diagnosis of polyps, cancer, or inflammatory bowel
      disease. CONCLUSIONS: Self-reported rectal bleeding detected by means of a review
      of systems was associated with a high likelihood of important pathology.
      Physicians should ask all adults about visible rectal bleeding and should
      visualize the entire colon in those who report bleeding.

PMID- 8980208
TI  - An outbreak of invasive group A streptococcal disease associated with high
      carriage rates of the invasive clone among school-aged children.
AB  - OBJECTIVES: To determine if a common strain of group A streptococcus was
      responsible for an outbreak of invasive streptococcal disease in southeastern
      Minnesota and to determine whether this strain was prevalent among residents of
      this area during the outbreak who either had streptococcal pharyngitis or were
      asymptomatic streptococcal carriers. DESIGN: Pharyngeal culture survey and case
      contact evaluation. SETTING: Three adjacent counties in southeastern Minnesota
      defined as the outbreak area. Outbreak period, January 1 through March 31, 1995.
      PATIENTS: Seven patients with invasive streptococcal infection, 1249 patients
      (adults and children) with sore throat who resided in the outbreak area, children
      from an elementary school located in 1 community where the majority of invasive
      cases occurred, and 896 students from 3 schools located in Minnesota counties
      outside the outbreak area. MEASUREMENTS: Pulsed-field gel electrophoresis (DNA
      fingerprinting) of group A streptococcal isolates obtained from patients with
      invasive disease, throat swabs of patients with sore throat, and throat swabs of
      asymptomatic school-aged children. RESULTS: All patients with outbreak-associated
      invasive disease had group A streptococcal isolates that were indistinguishable
      by pulsed-field gel electrophoresis. Additional testing showed that these
      isolates carried significant virulence factors including pyrogenic exotoxin A and
      streptococcal superantigen. Five of these 7 patients with invasive disease had
      underlying medical conditions; 4 developed toxic shock syndrome and died (case
      fatality, 57%). The outbreak-associated group A streptococcal clone was found in
      69 (26.5%) of the 260 patients with sore throat from whom group A streptococcus
      was isolated. The frequency of the outbreak clone among pharyngeal carriers from
      the 3 schools outside the outbreak area was significantly less (range, 0%-10%)
      than in children from the school in the outbreak area (78%; relative risk, 29;
      95% confidence interval, 11.1-78.1; P<.001). Four of the 7 patients with outbreak
      associated disease had contact with children who attended the school in the
      outbreak area. CONCLUSIONS: A single clone of group A streptococcus was
      responsible for 7 cases of invasive streptococcal disease during an outbreak in
      Minnesota and for a significant number of pharyngitis cases that also occurred
      during the outbreak. Invasive disease occurred most frequently in persons with
      underlying medical conditions. This outbreak was also associated with increased
      carriage rates of the invasive streptococcal clone among community school-aged
      children. Cases of invasive group A streptococcal infection may therefore reflect
      the tip of the iceberg with regard to the burden of colonization of a specific
      invasive streptococcal clone in a community.

PMID- 8980210
TI  - The impact of clinical history on mammographic interpretations.
AB  - OBJECTIVE: To determine whether mammographic interpretations are biased by the
      patient's clinical history. DESIGN: On 2 occasions, separated by a 5-month wash
      out period, 10 radiologists read mammograms for the same 100 women, randomly
      divided into 2 groups of 50. For 1 group, the clinical history was supplied for
      the first reading and omitted (except for age) for the second reading. This
      sequence was reversed in the other group. In addition, 5 cases were shown a third
      time with a deliberately leading sham history. PATIENTS: Selected with stratified
      random sampling from 3 categories of diagnostic findings (64 had mammographic
      abnormalities) and from the definitive designation of breast cancer or no breast
      cancer (18 had breast cancer). MAIN OUTCOME MEASURES: Radiologists' diagnostic
      accuracy and directional changes in interpretations and recommendations between
      the 2 readings. RESULTS: The direction suggested by the history led to small but
      consistent changes in the interpretations. Overall diagnostic accuracy was not
      altered, but recommendations were affected for appropriate further diagnostic
      workup: an alerting history (eg, breast symptoms or family history of breast
      cancer) increased the number of workups recommended in patients without cancer
      (P=.01); and a nonalerting history led to fewer recommended workups in the cancer
      patients (P=.02). The direction of the sham histories led an average of 4 of the
      10 radiologists to change previous diagnoses and an average of 1 radiologist to
      change a previous biopsy recommendation. CONCLUSIONS: Knowledge of the clinical
      history may alter a radiologist's level of diagnostic suspicion without improving
      performance in either diagnosis or management recommendations.

PMID- 8980211
TI  - Prevention of HIV/AIDS and other blood-borne diseases among injection drug users.
      A national survey on the regulation of syringes and needles.

PMID- 8980212
TI  - Should clinical trials with concurrent economic analyses be blinded?

PMID- 8980213
TI  - Physical activity and quality of life in older adults.

PMID- 8980214
TI  - Medical career choices in an era of change.

PMID- 8980215
TI  - The impending physician surplus: is it time to quit?

PMID- 8980217
TI  - Managed care's role in shaping the physician job market.

PMID- 8980216
TI  - Physician supply and the shifting paradigm of medical student choice.

PMID- 8980218
TI  - Alleviating the physician glut: what's the government's role?

PMID- 8980219
TI  - Spatial learning and memory: the beginning of a dream.

PMID- 8980220
TI  - Migraines in mice?

PMID- 8980221
TI  - Blood vessel formation: what is its molecular basis?

PMID- 8980222
TI  - Absconding with the chaperone: essential cyclophilin-Gag interaction in HIV-1
      virions.

PMID- 8980223
TI  - Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap
      expression cloning.
AB  - TIE2 is a receptor-like tyrosine kinase expressed almost exclusively in
      endothelial cells and early hemopoietic cells and required for the normal
      development of vascular structures during embryogenesis. We report the
      identification of a secreted ligand for TIE2, termed Angiopoietin-1, using a
      novel expression cloning technique that involves intracellular trapping and
      detection of the ligand in COS cells. The structure of Angiopoietin-1 differs
      from that of known angiogenic factors or other ligands for receptor tyrosine
      kinases. Although Angiopoietin-1 binds and induces the tyrosine phosphorylation
      of TIE2, it does not directly promote the growth of cultured endothelial cells.
      However, its expression in close proximity with developing blood vessels
      implicates Angiopoietin-1 in endothelial developmental processes.

PMID- 8980224
TI  - Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during
      embryonic angiogenesis.
AB  - Vascular endothelial growth factor (VEGF), which acts via members of a family of
      endothelial-specific receptor tyrosine kinases, is the only factor that has been
      shown definitively to play a role in the formation of the embryonic vasculature.
      Only one other family of receptor tyrosine kinases, comprising TIE1 and TIE2, is
      largely endothelial cell specific. We have recently cloned a ligand for TIE2,
      termed Angiopoietin-1. Here we show that mice engineered to lack Angiopoietin-1
      display angiogenic deficits reminiscent of those previously seen in mice lacking
      TIE2, demonstrating that Angiopoietin-1 is a primary physiologic ligand for TIE2
      and that it has critical in vivo angiogenic actions that are distinct from VEGF
      and that are not reflected in the classic in vitro assays used to characterize
      VEGF. Angiopoietin-1 seems to play a crucial role in mediating reciprocal
      interactions between the endothelium and surrounding matrix and mesenchyme.

PMID- 8980225
TI  - Vascular dysmorphogenesis caused by an activating mutation in the receptor
      tyrosine kinase TIE2.
AB  - Venous malformations (VMs), the most common errors of vascular morphogenesis in
      humans, are composed of dilated, serpiginous channels. The walls of the channels
      have a variable thickness of smooth muscle; some mural regions lack smooth muscle
      altogether. A missense mutation resulting in an arginine-to-tryptophan
      substitution at position 849 in the kinase domain of the receptor tyrosine kinase
      TIE2 segregates with dominantly inherited VM in two unrelated families. Using
      proteins expressed in insect cells, we demonstrate that the mutation results in
      increased activity of TIE2. We conclude that an activating mutation in TIE2
      causes inherited VMs in the two families and that the TIE2 signaling pathway is
      critical for endothelial cell-smooth muscle cell communication in venous
      morphogenesis.

PMID- 8980226
TI  - X-MyT1, a Xenopus C2HC-type zinc finger protein with a regulatory function in
      neuronal differentiation.
AB  - X-MyT1 is a C2HC-type zinc finger protein that we find to be involved in the
      primary selection of neuronal precursor cells in Xenopus. Expression of this gene
      is positively regulated by the bHLH protein X-NGNR-1 and negatively regulated by
      the Notch/Delta signal transduction pathway. X-MyT1 is able to promote ectopic
      neuronal differentiation and to confer insensitivity to lateral inhibition, but
      only in cooperation with bHLH transcription factors. Inhibition of X-MyT1
      function inhibits normal neurogenesis as well as ectopic neurogenesis caused by
      overexpression of X-NGNR-1. On the basis of these findings, we suggest that X
      MyT1 is a novel, essential element in the cascade of events that allows cells to
      escape lateral inhibition and to enter the pathway that leads to terminal
      neuronal differentiation.

PMID- 8980227
TI  - CREB phosphorylation and dephosphorylation: a Ca(2+)- and stimulus duration
      dependent switch for hippocampal gene expression.
AB  - While changes in gene expression are critical for many brain functions, including
      long-term memory, little is known about the cellular processes that mediate
      stimulus-transcription coupling at central synapses. In studying the signaling
      pathways by which synaptic inputs control the phosphorylation state of cyclic AMP
      responsive element binding protein (CREB) and determine expression of CRE
      regulated genes, we found two important Ca2+/calmodulin (CaM)-regulated
      mechanisms in hippocampal neurons: a CaM kinase cascade involving nuclear CaMKIV
      and a calcineurin-dependent regulation of nuclear protein phosphatase 1 activity.
      Prolongation of the synaptic input on the time scale of minutes, in part by an
      activity-induced inactivation of calcineurin, greatly extends the period over
      which phospho-CREB levels are elevated, thus affecting induction of downstream
      genes.

PMID- 8980228
TI  - MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required
      for nuclear accumulation and signaling.
AB  - MAD-related (MADR) proteins are essential intracellular components of TGFbeta
      signaling pathways and are regulated by phosphorylation. Here, we demonstrate
      that MADR2 and not the related protein DPC4 transiently interacts with the
      TGFbeta receptor and is directly phosphorylated by the complex on C-terminal
      serines. Interaction of MADR2 with receptors and phosphorylation requires
      activation of receptor I by receptor II and is mediated by the receptor I kinase.
      Mutation of the phosphorylation sites generates a dominant negative MADR2 that
      blocks TGFbeta-dependent transcriptional responses, stably associates with
      receptors, and fails to accumulate in the nucleus in response to TGFbeta
      signaling. Thus, transient association and phosphorylation of MADR2 by the
      TGFbeta receptor is necessary for nuclear accumulation and initiation of
      signaling.

PMID- 8980229
TI  - Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during
      Drosophila development.
AB  - Most cell types in multicellular eukaryotes exit from the mitotic cell cycle
      before terminal differentiation. We show that the dacapo gene is required to
      arrest the epidermal cell proliferation at the correct developmental stage during
      Drosophila embryogenesis. dacapo encodes an inhibitor of cyclin E/cdk2 complexes
      with similarity to the vertebrate Cip/Kip inhibitors. dacapo is transiently
      expressed beginning late in the G2 phase preceding the terminal division (mitosis
      16). Mutants unable to express the inhibitor fail to arrest cell proliferation
      after mitosis 16 and progress through an extra division cycle. Conversely,
      premature dacapo expression in transgenic embryos results in a precocious G1
      arrest.

PMID- 8980230
TI  - A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from
      the cell cycle during Drosophila embryogenesis.
AB  - In a screen for genes that interact with the Rap1 GTPase, we have identified a
      Drosophila gene, dacapo (dap), which is a member of the p21/p27 family of cdk
      inhibitors. Unlike mammalian cdk inhibitors studied to date, dap is essential for
      normal embryonic development. Dacapo inhibits cyclin-cdk activity in vitro.
      Overexpressing dap during eye development interferes with cell cycle progression
      and interacts genetically with the retinoblastoma homolog (Rbf) and cyclin E. dap
      expression in embryos parallels the exit of cells from the cell cycle. dap mutant
      embryos delay the normal cell cycle exit during development; many cells complete
      an additional cycle and subsequently become quiescent. Thus, dap functions during
      embryogenesis to achieve a precisely timed exit from the cell cycle.

PMID- 8980231
TI  - RSC, an essential, abundant chromatin-remodeling complex.
AB  - A novel 15-subunit complex with the capacity to remodel the structure of
      chromatin, termed RSC, has been isolated from S. cerevisiae on the basis of
      homology to the SWI/SNF complex. At least three RSC subunits are related to
      SWI/SNF polypeptides: Sth1p, Rsc6p, and Rsc8p are significantly similar to
      Swi2/Snf2p, Swp73p, and Swi3p, respectively, and were identified by mass
      spectrometric and sequence analysis of peptide fragments. Like SWI/SNF, RSC
      exhibits a DNA-dependent ATPase activity stimulated by both free and nucleosomal
      DNA and a capacity to perturb nucleosome structure. RSC is, however, at least 10
      fold more abundant than SWI/SNF complex and is essential for mitotic growth.
      Contrary to a report for SWII/SNF complex, no association of RSC (nor of SWI/SNF
      complex) with RNA polymerase II holoenzyme was detected.

PMID- 8980232
TI  - The TAF(II)250 subunit of TFIID has histone acetyltransferase activity.
AB  - The transcription initiation factor TFIID is a multimeric protein complex
      composed of TATA box-binding protein (TBP) and many TBP-associated factors
      (TAF(II)s). TAF(II)s are important cofactors that mediate activated transcription
      by providing interaction sites for distinct activators. Here, we present evidence
      that human TAF(II)250 and its homologs in Drosophila and yeast have histone
      acetyltransferase (HAT) activity in vitro. HAT activity maps to the central, most
      conserved portion of dTAF(II)230 and yTAF(II)130. The HAT activity of dTAF(II)230
      resembles that of yeast and human GCN5 in that it is specific for histones H3 and
      H4 in vitro. Our findings suggest that targeted histone acetylation at specific
      promoters by TAF(II)250 may be involved in mechanisms by which TFIID gains access
      to transcriptionally repressed chromatin.

PMID- 8980233
TI  - TAF(II)s mediate activation of transcription in the Drosophila embryo.
AB  - Mutations in the genes for two highly conserved TAFs, TAF(II)60 and TAF(II)110,
      reduce transcription of Bicoid-dependent target genes in vivo. By means of
      several distinct genetic test systems, specific activator-TAF interactions are
      shown to support both simple and synergistic enhancement of transcription in the
      embryo. These studies provide in vivo evidence that TAFs can serve as
      coactivators to receive gene-specific transcriptional activation signals. This
      genetic system also presents the opportunity to study the function of basal
      transcription components in regulating development of complex organisms.

PMID- 8980234
TI  - Crystal structure of human cyclophilin A bound to the amino-terminal domain of
      HIV-1 capsid.
AB  - The HIV-1 capsid protein forms the conical core structure at the center of the
      mature virion. Capsid also binds the human peptidyl prolyl isomerase, cyclophilin
      A, thereby packaging the enzyme into the virion. Cyclophilin A subsequently
      performs an essential function in HIV-1 replication, possibly helping to
      disassemble the capsid core upon infection. We report the 2.36 A crystal
      structure of the N-terminal domain of HIV-1 capsid (residues 1-151) in complex
      with human cyclophilin A. A single exposed capsid loop (residues 85-93) binds in
      the enzyme's active site, and Pro-90 adopts an unprecedented trans conformation.
      The structure suggests how cyclophilin A can act as a sequence-specific binding
      protein and a nonspecific prolyl isomerase. In the crystal lattice, capsid
      molecules assemble into continuous planar strips. Side by side association of
      these strips may allow capsid to form the surface of the viral core. Cyclophilin
      A could then function by weakening the association between capsid strips, thereby
      promoting disassembly of the viral core.

PMID- 8980235
TI  - Crystal structure of an IHF-DNA complex: a protein-induced DNA U-turn.
AB  - Integration host factor (IHF) is a small heterodimeric protein that specifically
      binds to DNA and functions as an architectural factor in many cellular processes
      in prokaryotes. Here, we report the crystal structure of IHF complexed with 35 bp
      of DNA. The DNA is wrapped around the protein and bent by >160 degrees, thus
      reversing the direction of the helix axis within a very short distance. Much of
      the bending occurs at two large kinks where the base stacking is interrupted by
      intercalation of a proline residue. IHF contacts the DNA exclusively via the
      phosphodiester backbone and the minor groove and relies heavily on indirect
      readout to recognize its binding sequence. One such readout involves a six-base A
      tract, providing evidence for the importance of a narrow minor groove.

PMID- 8980236
TI  - Recognition of the bacterial avirulence protein AvrBs3 occurs inside the host
      plant cell.
AB  - The molecular mechanism by which bacterial avirulence genes mediate recognition
      by resistant host plants has been enigmatic for more than a decade. In this paper
      we provide evidence that the Xanthomonas campestris pv. vesicatoria avirulence
      protein AvrBs3 is recognized inside the plant cell. Transient expression of
      avrBs3 in pepper leaves, using Agrobacterium tumefaciens for gene delivery,
      results in hypersensitive cell death, specifically on plants carrying the
      resistance gene Bs3. In addition, for its intracellular recognition, AvrBs3
      requires nuclear localization signals that are present in the C-terminal region
      of the protein. We propose that AvrBs3 is translocated into plant cells via the
      Xanthomonas Hrp type III secretion system and that nuclear factors are involved
      in AvrBs3 perception.

PMID- 8980237
TI  - Subregion- and cell type-restricted gene knockout in mouse brain.
AB  - Using the phage P1-derived Cre/loxP recombination system, we have developed a
      method to create mice in which the deletion (knockout) of virtually any gene of
      interest is restricted to a subregion or a specific cell type in the brain such
      as the pyramidal cells of the hippocampal CA1 region. The Cre/loxP recombination
      based gene deletion appears to require a certain level of Cre protein expression.
      The brain subregional restricted gene knockout should allow a more precise
      analysis of the impact of a gene mutation on animal behaviors.

PMID- 8980238
TI  - The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity
      in spatial memory.
AB  - We have produced a mouse strain in which the deletion of the NMDAR1 gene is
      restricted to the CA1 pyramidal cells of the hippocampus by using a new and
      general method that allows CA1-restricted gene knockout. The mutant mice grow
      into adulthood without obvious abnormalities. Adult mice lack NMDA receptor
      mediated synaptic currents and long-term potentiation in the CA1 synapses and
      exhibit impaired spatial memory but unimpaired nonspatial learning. Our results
      strongly suggest that activity-dependent modifications of CA1 synapses, mediated
      by NMDA receptors, play an essential role in the acquisition of spatial memories.

PMID- 8980239
TI  - Impaired hippocampal representation of space in CA1-specific NMDAR1 knockout
      mice.
AB  - To investigate the role of synaptic plasticity in the place-specific firing of
      the hippocampus, we have applied multiple electrode recording techniques to
      freely behaving mice with a CA1 pyramidal cell-specific knockout of the NMDAR1
      gene. We have discovered that although the CA1 pyramidal cells of these mice
      retain place-related activity, there is a significant decrease in the spatial
      specificity of individual place fields. We have also found a striking deficit in
      the coordinated firing of pairs of neurons tuned to similar spatial locations.
      Pairs have uncorrelated firing even if their fields overlap. These results
      demonstrate that NMDA receptor-mediated synaptic plasticity is necessary for the
      proper representation of space in the CA1 region of the hippocampus.

PMID- 8980241
TI  - Autonomy of the epithelial phenotype in human ovarian surface epithelium: changes
      with neoplastic progression and with a family history of ovarian cancer.
AB  - Epithelial ovarian carcinomas originate in the ovarian surface epithelium (OSE).
      In culture, OSE undergoes epithelio-mesenchymal conversion, an event mimicking a
      wound response, while ovarian carcinomas retain complex epithelial
      characteristics. To define the onset of this increased epithelial autonomy in
      ovarian neoplastic progression, we examined mesenchymal conversion in OSE from 25
      women with no family histories (NFH-OSE) and 13 women with family histories (FH
      OSE) of breast/ovarian cancer (including 8 with mutated BRCA1 or 17q linkage) and
      in 8 ovarian cancer lines. After 3-6 passages in monolayer culture, most NFH-OSE
      exhibited reduced keratin expression and high collagen type III expression. In
      contrast, keratin remained high but collagen expression was lower in p. 3-6 FH
      OSE. This difference was lost in SV40-transformed lines, which all resembled FH
      OSE. Most carcinoma lines remained epithelial and did not undergo mesenchymal
      conversion. In 3-dimensional (3-D) sponge culture, NFH-OSE cells dispersed and
      secreted abundant extracellular matrix (ECM). FH-OSE remained epithelial and did
      not secrete ECM. ECM production was also reduced in SV40-transformed lines.
      Carcinoma lines in 3-D formed epithelial cysts, aggregates and papillae and
      lacked ECM. Sponge contraction (a mesenchymal characteristic) was greater in NFH
      OSE than in FH-OSE both before and after SV40 transformation and was absent in
      the cancer lines. Our results suggest that increased autonomy of epithelial
      characteristics is an early indicator of ovarian neoplastic progression and that
      phenotypic changes indicative of such autonomy are found already in overtly
      normal OSE from women with histories of familial breast/ovarian cancer.

PMID- 8980240
TI  - Mice expressing activated CaMKII lack low frequency LTP and do not form stable
      place cells in the CA1 region of the hippocampus.
AB  - To relate different forms of synaptic plasticity to the formation and maintenance
      of place cells in the hippocampus, we have recorded place cells in freely
      behaving, transgenic mice that express a mutated Ca2+-independent form of CaM
      Kinase II. These mice have normal long-term potentiation (LTP) at 100 Hz, but
      they lack LTP in response to stimulation at 5-10 Hz and are impaired on spatial
      memory tasks. In these transgenic mice, the place cells in the CA1 region have
      three important differences from those of wild types: they are less common, less
      precise, and less stable. These findings suggest that LTP in the 5-10 Hz range
      may be important for the maintenance of place-field stability and that this
      stability may be essential for the storage of spatial memory.

PMID- 8980242
TI  - p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy
      and long-term prognosis.
AB  - In a series of 71 patients with advanced colorectal cancer treated with
      biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we
      investigated the relationship between the proliferating-cell nuclear antigen
      (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with
      respect to clinical response and long-term prognosis. Nuclear p53 expression was
      demonstrated in 44% of samples (any number of positive tumor cells) while all
      tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was
      correlated with histopathologic grade and p53 expression, while p53 was not
      correlated with any of the parameters considered. The probability of clinical
      response to biochemically modulated 5-FU was independent of p53 and PCNA
      expression. p53 expression (all cut-off values) was not associated with short- or
      long-term clinical prognosis, whereas patients with higher PCNA primary-tumor
      expression showed longer survival from treatment and survival from diagnosis,
      according to univariate and multivariate analysis, particularly in the sub-set of
      colon-cancer patients. We conclude that the clinical response of advanced
      colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be
      predicted by PCNA and p53 primary-tumor expression, but high PCNA expression
      appears to be independently related to long-term prognosis.

PMID- 8980243
TI  - An allelotype of papillary thyroid cancer.
AB  - Although papillary carcinoma accounts for approximately 70% of all thyroid
      cancers, preliminary studies of allelic loss have thus far not identified any
      areas of chromosomal deletion. We evaluated 30 papillary thyroid carcinomas for
      chromosomal loss/allelic imbalance by testing at least 2 microsatellite markers
      from every autosomal arm. Fifteen of the 30 tumors tested exhibited loss of
      heterozygosity/allelic imbalance (LOH/AI) at one or more loci. Chromosomal arms
      with frequent LOH/AI included 4q, 5p, 7p and 11p. An average of 1.1 chromosomal
      arms displayed LOH/AI in each individual tumor. Therefore, 4q, 5p, 7p and, to a
      lesser extent, 11p display significant LOH/AI in papillary thyroid cancer, which
      indicates the presence of putative tumor-suppressor gene loci at these
      chromosomal arms.

PMID- 8980244
TI  - Expression of tenascin in invasion border of early breast cancer correlates with
      higher risk of distant metastasis.
AB  - Tenascin (Tn) is an extracellular matrix glycoprotein transiently expressed in
      epithelial-mesenchymal interaction areas during embryogenesis. Tn is expressed in
      a limited manner in adult tissues but emerges during wound healing and
      tumorigenesis. We have studied Tn expression by immunohistochemistry in 137 small
      node-negative breast cancers treated with breast-conserving surgery and post
      operative radiotherapy during 1985-1989. None of the patients had undergone any
      adjuvant hormonal therapy or chemotherapy. Stromal Tn expression itself could not
      predict distant metastasis. However, Tn staining in the area of the invasion
      border seemed to be a strong predictor of distant metastasis, with an estimated 5
      year metastasis-free survival (MFS) of 85% in Tn-positive cases compared to 98%
      in Tn-negative ones. The prognostic impact of Tn in the invasion border on MFS
      was stronger than that of tumour size and grade. This staining appears to be a
      useful adjunct for the estimation of breast-cancer metastasis.

PMID- 8980246
TI  - Allelotype profiles of local recurrences and distant metastases from colorectal
      cancer patients.
AB  - Several genetic alterations have been described in benign and malignant primary
      tumors of the colorectum, but few such associations have been made with the
      progression of these tumors. This study compares genetic changes found in distant
      metastases (n = 22) with local recurrences (n = 15) as well as with primary
      carcinomas (n = 12). Complete allelotypes of the tumors were obtained by
      analyzing 43 microsatellite loci, representing all non-acrocentric chromosome
      arms and mapping to the mid-portion of the arms. Allelic imbalances in the tumor
      DNA were evaluated by comparison with the patient's constitutional pattern in
      blood DNA. The allelotype profile of the distant metastases was different from
      those found in the local recurrences and in the primary carcinomas. More than 20%
      of the distant metastases exhibited allelic imbalances at loci representing 20
      chromosome arms. The majority of these regions were less frequently changed in
      the local recurrences and in the primary tumors. The markers that most often were
      altered in the metastasis (>40%) represented chromosome arms 14q, 17p, 18p and
      18q. Only two regions, 10p and 19p, were unaltered in all tumors analyzed. We
      found that the median value of fractional allelic imbalance was twice as high in
      the distant metastases as in the recurrent tumors. Novel alleles at
      microsatellite loci were observed in all 3 tumor types, but in the advanced
      tumors this phenotype was characterized by only a single novel allele seen at
      less than 10% of the analyzed loci.

PMID- 8980245
TI  - High levels of stromelysin-3 correlate with poor prognosis in patients with
      breast carcinoma.
AB  - Stromelysin 3 (ST3) is a matrix metalloprotease (MMP) expressed in fibroblast
      like cells of most human invasive carcinomas. In this investigation, ST3 was
      measured by semiquantitative immunohistochemistry in 111 primary breast cancers.
      ST3 levels showed no correlation with tumor size, axillary-node status or tumor
      grade (Scarff-Bloom-Richardson system; SBR) but were significantly associated
      with higher nuclear grade (modified SBR). In addition, ST3 levels were
      significantly higher in ductal than in lobular cancers. Patients with high scores
      of ST3 staining had a shorter disease-free interval and shorter overall survival
      than patients with low scores. ST3 is thus one of the first MMPs to correlate
      with patient outcome in breast cancer. These findings are consistent with earlier
      clinical and experimental observations suggesting that ST3 contributes to breast
      cancer progression.

PMID- 8980247
TI  - Overexpression of MUC5 genes is associated with early post-operative metastasis
      in non-small-cell lung cancer.
AB  - Mucin glycoprotein can promote tumor-cell invasion metastasis and modulate the
      immune recognition of cancer. This study aimed to elucidate the clinical
      significance of mucin gene overexpression in lung cancer. We collected 60 lung
      cancer samples and paired non-tumorous lung portions of varying types and stages.
      Slot-blot analysis with specific anti-sense oligonucleotide probes derived from
      tandem repeat sequence of MUC1, -2, -3, -4, 5B and 5AC were utilized to compare
      the amount of mucin gene mRNA in tumor samples with that of the non-tumorous
      counterparts. A ratio higher than 1.5 for each specific mucin mRNA amount was
      considered to indicate mucin gene overexpression in tumors. Immunohistochemical
      staining of monoclonal antibodies against mature airway mucin (17Q2) and MUC1
      mucin protein (HMFG2) were also used to analyze mucin protein. The study showed
      that overexpression of mucin genes frequently occurred in lung cancer (25 out of
      60, 41.7%), but that there was no preferential expression of a particular mucin
      gene or a combination of mucin genes in these tumors. The overexpression of mucin
      genes and mucin protein had no correlation with tumor stage, nodal stage,
      histology or pathological differentiation grade. Tumors of smokers had higher
      MUC5B and MUC5AC mRNA expression ratios than those of non-smokers. Tumors with
      increased expression of mucin genes tended to be associated with post-operative
      relapse, especially when MUC5B and MUC5AC genes were overexpressed (p = 0.015 and
      0.025, respectively). The study suggests that overexpression of novel
      tracheobronchial mucin genes may result in an increased likelihood of post
      operative lung-cancer recurrence or metastases.

PMID- 8980248
TI  - Inactivation of p16/CDKN2 and p15/MTS2 genes in different histological types and
      clinical stages of primary ovarian tumors.
AB  - To define the involvement of p16/CDKN2 and p15/MTS2 inactivation in ovarian
      tumorigenesis and the association of these inactivation events with histological
      types and clinical stages of ovarian tumors, we analyzed homozygous deletion and
      somatic mutation of p16/CDKN2 and p15/MTS2 genes, as well as hypermethylation of
      the 5'-CpG island of the p16/CDKN2 gene, in 49 primary ovarian tumors and 6
      ovarian carcinoma cell lines. We found homozygous deletions of p16/CDKN2 and
      p15/MTS2 in 6 (12%) and 5 (10%) primary tumors, respectively. Somatic mutation of
      p16/CDKN2 was found in only 1 primary tumor, but mutation of p15/MTS2 was not
      detected in any sample. None of the 28 primary tumors or 6 cell lines was
      hypermethylated at the 5'-CpG island of p16/CDKN2. The incidence of inactivation
      of p16/CDKN2 in primary tumors was significantly higher in the advanced stages (7
      of 29) than in the early stages (0 of 14). Seven of 9 alterations in p16/CDKN2
      and p15/MTS2 were observed in serous (3 of 12), endometrioid (3 of 9) and clear
      cell (1 of 4) carcinomas. However, only normal sequences of these genes were
      detected in mucinous carcinomas. Loss of heterozygosity (LOH) at the IFNA locus
      was detected in 1 of 19 (5%) tumors, but no change at the D9S171 locus was
      observed in 17 tumors. These results suggest that: (i) homozygous deletion is the
      main mechanism of inactivation of p16/CDKN2 and p15/MTS2 in ovarian
      tumorigenesis; (ii) inactivation of p16/CDKN2 and p15/MTS2 may be the
      histological type-specific events involved in ovarian tumorigenesis; and (iii)
      inactivation of p16/CDKN2 is potentially involved in the progression of ovarian
      tumors in advanced stages.

PMID- 8980249
TI  - Hypermethylation of calcitonin gene regulatory sequences in human breast cancer
      as revealed by genomic sequencing.
AB  - DNA methylation has been studied intensively during the past years in order to
      elucidate its role in the regulation of gene expression, gene imprinting and
      cancer progression. Earlier studies have shown that a general genomic under
      methylation is associated with chronic lymphocytic leukemia and metastatic
      prostate cancer. Site-specific methylation changes, as revealed by the use of
      methylation-sensitive restriction enzymes, have been reported to occur in the
      promotor region of the calcitonin gene in chronic myeloid leukemia as it
      progresses from the chronic phase to blast crisis, in non-Hodgkin's lymphoid
      neoplasms and in non-lymphocytic leukemia. We have now explored possible
      methylation changes associated with benign and malignant breast tumors. Two
      approaches were employed: (i) chemical determination of general genomic
      methylation status and (ii) base-specific analysis of the methylation changes in
      the promoter of the calcitonin gene with the aid of genomic sequencing. The
      results did not reveal any changes of total DNA 5-methylcytosine content in
      ductal carcinoma of breast in comparison with benign tumors. There was a small,
      yet significant, increase in 5-methylcytosine content in lobular carcinoma.
      Genomic sequencing of the promoter region of the calcitonin gene, however,
      revealed a striking hypermethylation at or around the transcription start site of
      the gene in ductal carcinomas. In benign tumors and lobular carcinomas, this
      region was either entirely unmethylated or only slightly methylated. The latter
      changes may reflect a regional hypermethylation of the short arm of chromosome
      11, which harbors, in addition to the calcitonin gene, a number of putative or
      established tumor-suppressor genes. Our results demonstrate that genomic
      sequencing in its present form can be used for a reliable and precise DNA
      methylation analysis of primary human tumors.

PMID- 8980250
TI  - Expression of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1
      in benign, borderline, malignant primary and metastatic ovarian tumors.
AB  - Elevated levels of expression of the urokinase-type plasminogen activator (uPA)
      and its inhibitor PAI-1 have shown to be related to poor prognosis in a variety
      of cancer types. In the present study, cytosolic levels of uPA and PAI-1 were
      determined with enzyme-linked immunosorbent assays in cytosols prepared from 244
      human ovarian tissues of different histological sub-types. Both uPA and PAI-1
      were significantly associated with the malignant progression of ovarian tissues;
      the levels were increased going from normal tissue, via benign and borderline
      adenomas, to primary and metastatic adenocarcinomas. For the 90 patients (34
      early-stage and 56 patients with advanced disease) from whom the primary
      adenocarcinoma tissues were examined, uPA and PAI-1 levels were evaluated for
      their association with clinicopathological parameters and with progression-free
      and overall survival. Neither uPA nor PAI-1 were significantly associated with
      the age of the patient, FIGO stage, tumor grade, tumor rest, the presence of
      ascites, or with progression-free or overall survival. On the other hand, age,
      FIGO stage/tumor rest and the presence of ascites, were significantly related to
      the length of both progression-free and overall survival in univariate analyses.
      Tumor grade was of prognostic significance in the analysis for progression-free
      survival, but not for overall survival. After adjustment for FIGO stage/tumor
      rest, only age retained its prognostic significance, in the analysis for
      progression-free survival and in that for overall survival.

PMID- 8980251
TI  - Microsatellite instability in B-cell lymphoma originating from Bloom syndrome.
AB  - Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized
      by lupus-like erythematous telangiectasias of the face, sun sensitivity, stunted
      growth infertility and immunodeficiency. In addition, BS patients are highly
      predisposed to cancers. Although recently the causative gene of BS (BLM) was
      identified as a DNA helicase homologue, the function of BLM in DNA replication
      has not been elucidated. In this study, p53 mutation and microsatellite
      instability in B-cell lymphomas originating from 2 sibling BS patients were
      investigated. In the originally developed tumor of both patients, no p53 mutation
      was detected. In one patient, however, after treatment by ionizing radiation the
      B-cell lymphoma recurred, showing a 9-bp deletion in exon 7. In lymphoma cells
      and an EB-virus-transformed cell line from BS lymphocytes of this patient,
      microsatellite instability was also detected from the reduced length of
      microsatellite DNA markers, although in the other patient microsatellite
      instability was not detected. Thus, 2 B-cell lymphomas, despite having the same
      BLM mutation, showed different phenotypes in terms of p53 mutation and
      microsatellite instability.

PMID- 8980252
TI  - Instability of chromosome 6 microsatellite repeats in human cervical tumors
      carrying papillomavirus sequences.
AB  - Loss of heterozygosity (LOH) in chromosome 6 in human squamous cervical
      carcinomas was analyzed in the long and short arms of the chromosome using 3
      pairs of primers each. In all cases, normal adjacent tissue was used as control.
      Among 51 cases analyzed, we identified LOH or microsatellite instability in 23%
      using primer D6S291 (located at position 6p21.3) and in 11% using primers D6S308
      (6q16.3-6q27) and D6S270 (6q22.3-6q23.2). On the contrary, no significant LOH or
      genomic instabilities were detected with primers D6S306 (6p22.3-6p21.2), D6S299
      (6p22.3-6p21.3) and D6S287 (6q21-6q23.3). Our results thus suggest the existence
      of instable loci at 3 regions of chromosome 6. Whether these loci contain
      putative tumor-suppressor genes or genes involved in cell cycle control remains
      unknown.

PMID- 8980253
TI  - Expression of the multidrug resistance-associated protein (MRP) gene in
      urothelial carcinomas.
AB  - The intrinsic or acquired resistance of urothelial cancer to chemotherapy is one
      major obstacle to successful treatment. Generally, the expression level of P
      glycoprotein in urothelial cancer is low, so we accordingly investigated the
      expression of multidrug resistance-associated protein (MRP). We examined the
      expression of MRP mRNA by means of slot-blotting samples of 11 renal pelvic
      and/or ureteral tumors, 33 bladder tumors, one lung metastasis from a ureter
      tumor, 7 non-cancerous urothelia from patients with transitional-cell carcinoma
      (TCC) and one urothelium from a patient with renal-cell carcinoma (RCC). We also
      estimated, by Southern blotting, whether or not the MRP gene was amplified in
      clinical specimens that overexpressed MRP mRNA. MRP was detected
      immunohistochemically using a polyclonal antibody against MRP. In all, 5 of 11
      renal pelvic and/or ureter tumors (45.5%), 17 of 33 bladder tumors (51.5%) and 4
      of 7 non-cancerous urothelia of TCC patients (57.1%) expressed more than 2-fold
      the MRP mRNA levels of drug-sensitive human KB cells. There was no significant
      difference in the MRP mRNA level between primary and recurrent tumors. Low-grade
      urothelial carcinomas (G1 and G2 TCCs) expressed significantly higher levels of
      MRP mRNA than the high-grade G3 TCC. The MRP gene was not amplified in urothelial
      carcinomas, irrespective of their expression levels of MRP mRNA.
      Immunohistochemically, MRP was located mainly on the plasma membrane, but also
      detected on the cytoplasm of cancer cells. MRP may be one mechanism responsible
      for intrinsic drug resistance in low-grade urothelial cancer.

PMID- 8980254
TI  - Lineage- and differentiation stage-specific expression of LSM-1 (LPAP), a
      possible substrate for CD45, in human hematopoietic cells.
AB  - CD45, a transmembrane tyrosine phosphatase, is found on almost all nucleated
      hematopoietic cells and plays a crucial role in lymphocyte activation and
      differentiation. We recently achieved isolation of the human LSM-1 (hLSM-1) gene,
      whose product is a possible substrate for CD45, and we raised antibodies against
      the hLSM-1 protein. hLSM-1 expression in hematopoietic cells was examined with
      Northern and Western blot, fluorescence-activated cell sorter, and
      immunocytochemical analyses. It was found that in the lymphoid lineage, T and B
      lymphocytes as well as NK cells expressed LSM-1, whereas terminally
      differentiated plasma cells did not. As for the myeloid lineage, immature myeloid
      cells expressed LSM-1, whereas terminally differentiated granulocytes and
      monocytes did not. In the erythroid lineage, normal erythroblasts expressed very
      low levels of LSM-1, while erythroid cell lines (K562 and HEL) did not.
      Megakaryocytes did not express LSM-1. Both CD34+/CD33- and CD34+/CD33+
      hematopoietic progenitor cells weakly expressed LSM-1. These results showed that
      LSM-1 is expressed in a lineage- and differentiation stage-specific fashion.

PMID- 8980255
TI  - Factor V Leiden is not responsible for stroke in patients with sickling disorders
      and is uncommon in African Americans with sickle cell disease.
AB  - Cerebrovascular accidents in patients with sickle cell anemia are among the most
      devastating complications of the disease. It has recently been demonstrated that
      some patients have a hypercoagulable state on the basis of the presence of an
      abnormal factor V molecule, factor V Leiden. We undertook this study to evaluate
      the presence of factor V Leiden in sickle cell patients with stroke. Eighty-two
      patients with either Hgb SS, Hgb SC, or Hgb S(beta+)-thalassemia comprised the
      study population. Of the 82 patients in the study, 19 of them had a history of
      stroke. In our study population, none of the stroke patients possessed the factor
      V Leiden mutation. One of the non-stroke patients was a heterozygote for the
      mutation (P = 1.00). The overall frequency of the factor V Leiden allele in our
      population is 0.6%. The estimated prevalence for this mutation is reportedly
      between 3 and 7% in Caucasian populations. We conclude that the gene frequency
      for factor V Leiden is less common in Africa Americans with sickle cell disease.
      Furthermore, factor V Leiden does not appear to be responsible for the
      development of stroke in sickle cell patients.

PMID- 8980256
TI  - Genetic analysis of beta-thalassemia intermedia in Israel: diversity of
      mechanisms and unpredictability of phenotype.
AB  - Molecular analysis was performed on 95 Israeli patients with thalassemia
      intermedia, representing 60 families of Arab (Moslem and Christian), Jewish,
      Druze, and Samaritan origin. There was a wide range of phenotypic severity, with
      baseline hemoglobin levels ranging from 5.5 to 10.7. Eighteen thalassemia
      mutations were found (29 genotypes), which were subdivided into groups, according
      to the severity of mutations. A consistently mild phenotype (10 families) was
      caused by compound heterozygosity for a silent mutation, such as -101 C-T or by
      coexistence of triplicated alpha-globin genes with thalassemia trait. In 39
      thalassemia intermedia families, the genotype which was found was one which led
      to severe thalassemia intermedia, or, in other families, was associated with
      thalassemia major. Elevated hemoglobin F ameliorated the disease in some patients
      with a severe genotype. We did not find a beneficial effect of concurrent alpha
      thalassemia in any of the families studied. In 11 families, only one beta
      thalassemia allele was identified. One was a dominant thalassemia intermedia
      allele. Three additional families with heterozygous beta-thalassemia had excess
      alpha-globin genes (5 or 6 total). In 7 of these heterozygotes, no explanation
      was found for the thalassemia intermedia phenotype. Our results suggest a
      substantial influence of as yet unknown genetic modifiers. These findings have
      important implications for prenatal diagnosis and for the genetic counseling of
      families with thalassemia intermedia.

PMID- 8980257
TI  - Fibrinolysis, inhibitors of blood coagulation, and monocyte derived coagulant
      activity in acute malaria.
AB  - Different parameters of fibrinolytic systems like t-PA, PAI, D-dimer, and
      inhibitors of blood coagulation, i.e., protein C (PC), protein S(PS), and
      antithrombin III (AT-III), have been studied in cases of acute malaria due to
      Plasmodium falciparum and plasmodium vivax infection, and these patients were
      followed up. It was observed that the plasma PAI-1 was very high in cases of P.
      falciparum malaria infection as compared to normal controls and P. vivax
      infection. The changes in complicated cases of P. falciparum were remarkable as
      compared to uncomplicated ones. The PC, PS, and AT-III levels were also low in P.
      falciparum, particularly so in complicated cases, and were normal in P. vivax
      infection. The factor VIII R:Ag levels were invariably high in acute malaria. On
      follow-up of some of these cases the values came back to normal after the
      antiparasite treatment. The monocyte procoagulant activity was found to be
      significantly higher in P. falciparum infection as compared to that of P. vivax
      infection. All these findings therefore contribute towards the production of a
      hypercoagulable state in P. falciparum infection and partly explain the
      complications of P. falciparum infection like cerebral malaria.

PMID- 8980258
TI  - Properties of the mouse alpha-globin HS-26: relationship to HS-40, the major
      enhancer of human alpha-globin gene expression.
AB  - HS-26, the mouse homologue of HS-40, is the major regulatory element of the mouse
      alpha-globin gene locus. Like HS-40, HS-26 is located within an intron of a house
      keeping gene; comparison of the nucleotide sequences of HS-26 and HS-40 reveals
      conservation of the sequences and positions of several DNA binding motifs in the
      5' regions of both elements (3 GATA, 2 NFE-2, and 1 CACCC sites) and the absence
      in HS-26 of three CACCC sites and one GATA site that are present in the 3' region
      of HS-40, suggesting that the two elements might not be identical. We report here
      that when HS-26 is linked to a 1.5 kb Pstl human alpha-globin gene fragment, it
      has a weak enhancer activity in induced MEL cells and in transgenic embryos, and
      it does not have any detectable activity in adult transgenic mice. This suggests
      that HS-26 does not have Locus Control Region (LCR) activity but can act as an
      enhancer during the embryonic life when integrated at a permissive locus. To
      further test the importance of HS-26 at its natural locus, we have generated
      embryonic stem cells and chimeric animals in which 350 bp containing HS-26 have
      been replaced by a neomycin resistance gene by homologous recombination. The
      sizes of the chimeras' red cells were then estimated by measuring forward
      scattering on a FacsScan apparatus in hypotonic conditions. This revealed that a
      fraction of the chimeric animals' red cells were smaller than normal mouse red
      cells and were very similar to cells from mice heterozygous for alpha
      thalassemia. Density gradient analysis also suggested the presence of thalassemic
      cells. These results indicated that despite its lack of LCR activity, HS-26 is
      important for the regulation of the mouse alpha-globin gene locus.

PMID- 8980259
TI  - Quantitative analysis of erythrocytes containing fetal hemoglobin (F cells) in
      children with sickle cell disease.
AB  - Variation in the level of fetal hemoglobin (HbF) accounts for much of the
      clinical heterogeneity observed in patients with sickle cell disease (SCD). The
      HbF level has emerged as an important prognostic factor in both sickle cell pain
      and mortality, and a % HbF of 10-20% has been suggested as a threshold level for
      diminished clinical severity. The number of erythrocytes that contain HbF (termed
      F cells) may also be critically important, as F cells resist intravascular
      sickling and have preferential in vivo survival. Since F cells can be enumerated
      with high accuracy using flow cytometry methods, we prospectively studied a
      cohort of 242 children with SCD. Children with HbS and hereditary persistence of
      fetal hemoglobin (S/HPFH) had essentially 100% F cells. In contrast, children
      with homozygous sickle cell anemia (HbSS), HbS/beta0 thalassemia, or HbS/beta+
      thalassemia had significantly lower mean % F cell values (55.9, 61.6, and 51.3%,
      respectively; P < 0.001), and children with HbSC had even fewer F cells (27.0%; P
      < 0.001). There was a highly significant correlation between the % F cells and
      the log (% HbF), which was observed for the total population of children (r =
      0.95, P < 0.001), as well as for each of the individual subgroups of children
      with HbSS (r = 0.94, P < 0.001), HbSC (r = 0.89, P < 0.001), or HbS/beta0
      thalassemia and HbS/beta+ thalassemia (r = 0.95, P <0.001). This logarithmic
      correlation between % F cells and % HbF has not been previously described and has
      important implications for the pharmacologic manipulation of HbF in patients with
      SCD.

PMID- 8980260
TI  - Improved method for diagnosis of polycythemia vera based on flow cytometric
      analysis of autonomous growth of erythroid precursors in liquid culture.
AB  - "Autonomous" development of erythroid colonies in erythropoietin (EPO)-free semi
      solid culture has been used as an in vitro assay for diagnosis of polycythemia
      vera (PV). These colonies, however, are small and poorly hemoglobinized,
      rendering the assay in many cases unreliable. We report here on the use of a
      novel assay; it combines a modified culture procedure that maximizes the growth
      of EPO-independent erythroid cells, and immunofluorescence flow cytometry for
      their detection and quantitation. Peripheral blood mononuclear cells are cultured
      for 2-5 days in the presence of a combination of growth factors. During this
      phase, early erythroid committed progenitors, burst forming units (BFUe),
      proliferate and differentiate into colony forming units (CFUe)-like progenitors.
      In the second phase, the latter cells, in the presence of stem cell factor,
      hemin, and iron-saturated transferrin, continue to proliferate and mature into
      hemoglobin (Hb)-containing orthochromatic normoblasts. Neither phases contained
      EPO. The culture produced large, pure, and synchronized erythroid cell
      populations. The cells were then dually labeled with fluorescent probes, nuclear
      DNA with thiazole orange and intracellular hemoglobin (Hb) with phycoerythrin
      conjugated monoclonal antibodies against human Hb. Cells positive for both labels
      were assigned as Hb-containing nucleated precursors. The presence of such cells
      in EPO-free cultures indicated "autonomous growth." None of the EPO-free cultures
      derived from normal donors or patients with secondary polycythemia contained such
      cells. Cultures derived from PV patients contained from 5 to 92% "autonomously
      grown" cells. These culture and analysis methods should minimize false negative
      results with PV patients and provide objective and quantitative data.

PMID- 8980261
TI  - Inherited thrombotic disorders: an update.
AB  - Significant advances in identification of etiologies of inherited thrombosis have
      been recently reported. A point mutation in coagulation factor V (factor V
      Leiden) results in resistance to activated protein C and probably represents the
      most common genetic risk factor for venous thrombosis. A metabolic disorder,
      homocysteinemia, is now known to be an important risk factor for both arterial
      and venous thrombosis. Many patients with recurrent thrombosis will have more
      than one genetic risk factor identified. Recognition of these new disorders
      should permit a diagnosis to be achieved in at least half of patients evaluated
      for inherited thrombosis.

PMID- 8980262
TI  - Chronic myeloid leukemia as an immunological target.
AB  - Various clinical observations have implicated T cells in the control of chronic
      myeloid leukemia (CML). These observations have in recent years been supported by
      laboratory results indicating the presence of CML-specific T cells in the
      lymphocyte repertoire of both normal healthy individuals and disease-bearing
      patients. Both MHC-unrestricted and MHC-restricted immune effector mechanisms are
      involved. Donor lymphocyte infusion has produced encouraging GvL effects.
      However, future adoptive immunotherapy may depend on the isolation and generation
      of leukemia-specific T cells. Although many proteins may potentially act as
      leukemia antigens in CML for MHC-restricted cytotoxicity, the bcr-abl fusion
      protein has been most extensively investigated. There is now much evidence to
      suggest that the bcr-abl junctional peptides are capable of eliciting both CD4
      and CD8 responses in normal healthy donors and CML patients. Furthermore, the T
      cell lines generated react with autologous or HLA-matched fresh CML cells,
      suggesting that the bcr-abl fusion protein can be processed in vivo so that the
      joining segment is bound to HLA molecules in a configuration and concentration
      similar to those of the immunizing peptide for antigen recognition by the antigen
      specific T-cell receptor. These results also indicate that the bcr-abl junctional
      peptides may be used for immunotherapy of CML. Other strategies available for
      immunotherapy of CML include immunologically or genetically manipulated donor T
      cell infusion, the use of cytokines, adoptive immunotherapy with leukemia
      reactive T-cells expanded ex vivo, and immune gene therapy. Novel and rational
      immunotherapy may therefore play an important adjuvant role in future in the
      management of patients with CML.

PMID- 8980263
TI  - Normalization of plasma factor X levels in amyloidosis after plasma exchange.
AB  - Some patients with systemic light chain amyloidosis develop bleeding
      complications that can be caused by vascular infiltration with amyloid or by
      alterations of the coagulation or fibrinolytic systems. Factor X deficiency is
      the most common cause of bleeding manifestations, although deficiencies of other
      clotting factors, a disruption in the conversion of fibrinogen to fibrin, and
      circulating heparin-like anticoagulants have also been reported. Deficiency of
      factor X is a well-recognized cause of bleeding manifestations in patients with
      light chain amyloidosis. This acquired disorder appears to be secondary to
      adsorption of factor X to the amyloid fibrils. Previous studies have shown that
      infusion of plasma into patients with acquired factor X deficiency and
      amyloidosis induces a transitory improvement of the coagulation tests. However,
      there is a rapid return to pretransfusion levels. In this manuscript we report
      the clinical application of plasma exchange in the management of a patient with
      systemic light chain amyloidosis with acquired factor X deficiency.

PMID- 8980264
TI  - Deletion of the long arm of chromosome 20 in a patient with chronic neutrophilic
      leukemia: cytogenetic findings in chronic neutrophilic leukemia.
AB  - We encountered a 67-year-old female with chronic neutrophilic leukemia (CNL).
      Cytogenetic study showed she had a deletion in the long arm of chromosome 20.
      This finding indicates that CNL, in this case, is a clonal disorder. Most CNL
      patients have normal karyotypes, and only four patients with cytogenetic
      abnormalities, including two cases who received chemotherapy before the
      cytogenetic abnormality was detected, have been reported. Four of those cases,
      including our case, had abnormalities in the long arm of chromosome 20. This
      locus may be associated with the development of CNL. To our knowledge, this is
      the first case with CNL who showed deletion of the long arm of chromosome 20
      before treatment was started.

PMID- 8980265
TI  - Beta-globin haplotypes from blood spots for follow-up of newborn hemoglobinopathy
      screening.
AB  - The inheritance of sickle-cell anemia upon the background of the major beta
      globin gene cluster haplotypes has been associated with differing risks for major
      organ failure, and more recently with response to hydroxyurea treatment. Early
      identification of beta-globin haplotypes in individuals with sickle-cell anemia
      may be a clinically useful prognostic factor for severity of disease expression.
      This report describes the use of whole-blood spots on filter papers from newborn
      hemoglobinopathy screening for beta-globin gene cluster haplotyping by the
      polymerase chain reaction.

PMID- 8980266
TI  - Primary cardiac lymphoma.
AB  - Primary cardiac lymphoma is a rare entity. We report on the clinicopathological
      features of 2 patients with primary cardiac lymphomas: one involving the right
      atrium resulting in intractable right heart failure, and the other involving the
      pericardium with massive pericardial effusion. In the first patient, sternotomy
      and surgical biopsy of the tumor were performed to arrive at the diagnosis. In
      the second patient, CT thorax and transesophageal echocardiography helped to
      diagnose the pericardial tumor, and cytological examination of the pericardial
      fluid established the pathological diagnosis of lymphoma. Combination
      chemotherapy (COPP) was started in both patients. The first patient died on the
      first day of chemotherapy due to intractable heart failure, while the second
      attained a partial response to chemotherapy but died of progressive disease 8
      weeks later. This is followed by a literature review of 21 patients with primary
      cardiac lymphoma. In conclusion, the prognosis of primary cardiac tumor remains
      poor.

PMID- 8980267
TI  - Case of Schwachman's syndrome with intermittent neutropenia and lymphocyte subset
      disturbances.

PMID- 8980268
TI  - Prothrombin deficiency and hemorrhage associated with a lupus anticoagulant.

PMID- 8980269
TI  - Tumor lysis syndrome in a case of chronic lymphocytic leukemia induced by high
      dose corticosteroids.

PMID- 8980270
TI  - Detection of HTLV-I proviral DNA by fluorescence in situ hybridization.

PMID- 8980271
TI  - Philadelphia chromosome-positive acute lymphoblastic leukemia after therapy for
      Langerhans cell histiocytosis.

PMID- 8980272
TI  - Hemophagocytic syndrome responding to high-dose gammaglobulin as presenting
      feature of sarcoidosis.

PMID- 8980273
TI  - Sideroblastic anemia terminating in chronic myeloid leukemia.

PMID- 8980274
TI  - Residual leukemic blasts or regenerating normal precursors? The hematologist's
      dilemma.

PMID- 8980275
TI  - Recurrent reversible nephrotic syndrome during therapy with recombinant
      interferon alpha.

PMID- 8980276
TI  - Aleukemic leukemia cutis preceding overt acute myeloid leukemia in
      myelodysplastic syndrome.

PMID- 8980277
TI  - Direct correlation between DNA repair capacity and metastatic potential of K-1735
      murine melanoma cells.
AB  - The purpose of this study was to determine whether the ability of K-1735 murine
      melanoma cells to repair DNA damage correlates with their metastatic potential.
      Three nonmetastatic clones, four metastatic clones, and three somatic-cell
      hybrids between metastatic and nonmetastatic clones were exposed to incident
      ultraviolet (UV) light (254 nm). Cell survival was determined by the microculture
      tetrazolium assay, which measures cell metabolic activity. DNA repair capacity
      was determined with a host-cell reactivation assay, which measures the activities
      of chloramphenicol acetyltransferase encoded by the reporter gene in both UV
      damaged and undamaged plasmid (control) pCMV cat 40 h after transfection. No
      discernible differences in transfection efficiencies were found between K-1735
      clones with low and high metastatic potential or between cells transfected with
      UV-damaged and control plasmids. DNA repair capacity directly correlated with
      cell survival (p < 0.05) and with metastatic potential in the K-1735 clones and
      somatic cell hybrids (p < 0.05). These data suggest that the intrinsic resistance
      of melanoma metastases to systemic chemotherapy may be due, in part, to the
      cells' enhanced DNA repair capacity.

PMID- 8980278
TI  - Urokinase plasminogen activator is expressed by basal keratinocytes before
      interstitial collagenase, stromelysin-1, and laminin-5 in experimentally induced
      dermatitis herpetiformis lesions.
AB  - We studied the temporal expression of interstitial collagenase, stromelysin-1 and
      -2, and urokinase plasminogen activator (uPA) mRNAs by in situ hybridization in
      eight patients with dermatitis herpetiformis. To induce blisters, 50% potassium
      iodide patch tests were performed, and serial biopsy specimens were taken at 4,
      12, and 24 h. Additional samples were taken from occasional spontaneous blisters.
      Components of the basement membrane, laminin-5, laminin-1, and type VII collagen,
      were examined immunohistochemically in relation to matrix metalloproteinase
      expression. At 12 h, when no blisters were seen, uPA mRNA was present in basal
      keratinocytes in five of eight samples, whereas interstitial collagenase and
      stromelysin-1 mRNA were not detected. At this time, immunohistochemistry failed
      to show changes in the basement membrane. At 24 h, uPA, collagenase, and
      stromelysin-1 mRNAs were present in basal keratinocytes, suggesting an activation
      of latent forms of the two latter enzymes by the uPA-plasmin pathway. Signal for
      stromelysin-2 was not detected. Furthermore, disruptions of laminin-1 and type
      VII collagen were evident. The data suggest that stromelysin-1 and interstitial
      collagenase may contribute to the degradation of basement membrane in dermatitis
      herpetiformis. Intracellular staining for laminin-5 co-localized with collagenase
      mRNA in basal keratinocytes. Because laminin-5 is essential for adhesion of
      keratinocytes to basement membrane and for establishment of focal adhesions on
      migrating cells, its production may reflect a regenerative response after the
      destruction of basement membrane components.

PMID- 8980279
TI  - Involucrin and SPRR are synthesized sequentially in differentiating cultured
      epidermal cells.
AB  - Epidermal keratinocytes form cornified cell envelopes during terminal
      differentiation. These envelopes are composed of several cross-linked molecules,
      including involucrin, loricrin, and SPRR. We have previously reported that
      involucrin is synthesized earlier in terminal differentiation than loricrin. To
      further elucidate the mechanisms of terminal differentiation, we have now
      examined the expression of the two differentiation markers, involucrin and SPRR,
      in cultured human epidermal keratinocytes. In confluent nonstratified cultures,
      many involucrin-immunoreactive cells were detected, but few SPRR1/3-positive
      cells. Double staining demonstrated that cells containing SPRR1/3 almost always
      contained involucrin, but involucrin was present in many cells that did not
      contain SPRR. Light and electron microscopic immunohistochemistry of a stratified
      culture demonstrated that lower cells (close to the basal layer) were
      occasionally involucrin-positive, but lacked SPRR1/3, whereas more superficial
      cells contained both involucrin and SPRR. We conclude that involucrin and SPRR
      are sequentially induced in this order during keratinocyte differentiation.

PMID- 8980280
TI  - The spectral dependence for UVA-induced cumulative damage in human skin.
AB  - The wavelength dependence for UVA-induced cumulative damage was investigated in
      human skin. Epidermal changes (stratum corneum thickening, viable epidermal
      thickening sunburn cell production), as well as dermal alterations (lysozyme
      deposition, inflammation), were used as indices of cumulative photoperturbation.
      UVA wavelengths between 320 nm and 345 nm were more effective than longer
      wavelengths (360-400 nm) in inducing viable epidermal thickening. Similarly, the
      shorter wavelengths (320-345 nm) elicited more sunburn cells, although these
      differences did not reach statistical significance. All UVA bands were equally
      effective in inducing the dermal markers. At equal fluences, wavelengths > 400 nm
      produced no measurable cutaneous alterations. These findings suggest that (i)
      chronic epidermal and dermal damages have different spectral dependence and (ii)
      the action spectrum for dermal damage in the UVA is broad, extending up to 400
      nm, and is different from the acute erythema spectrum in humans.

PMID- 8980281
TI  - Chromosomal abnormalities in cutaneous T-cell lymphoma and in its premalignant
      conditions as detected by G-banding and interphase cytogenetic methods.
AB  - The etiology of cutaneous T-cell lymphomas (CTCL) is unknown. We studied the
      pattern of chromosomal abnormalities with G-banding and interphase in situ
      hybridization methods in blood mononuclear cells in 17 patients representing the
      different phases of CTCL or the premalignant condition, parapsoriasis en plaque,
      and in 10 control persons. We used biotinylated centromere-specific probes with
      fluorescent detection (FISH) for chromosomes 1, 11, 8, and 17 and similar,
      enzymatically detectable, digoxigenin-labeled probes for chromosomes 1, 6, 12,
      17, and 18. In G-banding, all patients showed numerical and structural chromosome
      aberrations. Numerical aberrations of chromosomes 6, 13, 15, and 17, marker
      chromosomes, and structural aberrations of chromosomes 3, 9, and 13 were
      increased in mycosis fungoides (MF) compared with healthy controls. In four of
      five patients the detection of a chromosomal clone preceded relapse or
      progression of the disease. In FISH of interphase cells, the cells abnormal for
      chromosomes 8 or 11, and for all four chromosomes collectively, were increased in
      MF and in Sezary Syndrome (SS). FISH and G-banding methods agreed statistically
      significantly for the detection of monosomy. Also, digoxigenin-labeled probes
      hybridized to interphases or mitoses detected aberrations corresponding to those
      observed with G-banding. Thus, chromosomally abnormal cells can be found in the
      peripheral blood of both parapsoriasis en plaque and CTCL patients. They can be
      detected with interphase cytogenetical methods, which obviates the need for
      dividing cells, often difficult to accomplish in CTCL.

PMID- 8980283
TI  - A homozygous nonsense mutation and a combination of two mutations of the Wilson
      disease gene in patients with different lysyl oxidase activities in cultured
      fibroblasts.
AB  - Wilson disease is a rare autosomal recessive disease of copper metabolism. The
      gene for Wilson disease was characterized recently and has been predicted to
      encode a copper-transporting ATPase highly homologous to the protein encoded by
      the gene of Menkes disease. In this study, the genetic mutations of two Finnish
      patients with Wilson disease were investigated. One patient was homozygous for a
      novel nonsense mutation in exon 4, while the other was a compound heterozygote.
      Lysyl oxidase (EC 1.4.3.13) is an extracellular copper enzyme with deficient
      activity in Menkes disease. The levels of lysyl oxidase activity in cultured skin
      fibroblasts from these Wilson disease patients were also measured.

PMID- 8980282
TI  - Complementation of hypopigmentation in p-mutant (pink-eyed dilution) mouse
      melanocytes by normal human P cDNA, and defective complementation by OCA2 mutant
      sequences.
AB  - Mutations in the P gene of humans and the homologous p-locus of mice,
      respectively, result in the homologous disorders oculocutaneous albinism type 2
      (OCA2) and pink-eyed dilution. Although clearly required for melanin
      biosynthesis, the specific function of the P gene product, a melanosomal
      transmembrane protein expressed in melanocytes of the skin, hair, and eyes, is
      not yet known. Here we describe lines of immortal melanocytes and melanoblasts
      from mice of the null genotype p(cp)/p(25H). These p-null melanocytes were
      severely hypopigmented, although they and the melanoblasts expressed mRNAs for a
      number of melanosomal proteins. Proliferation of the p-null melanoblasts was
      normal. Both diploid and immortal p-null melanocytes grew more slowly than wild
      type melanocytes, however, and were unusually susceptible to the antibiotic G418;
      these abnormalities were corrected by culture in high concentrations of L
      tyrosine. Transfection of the p-null melanocytes with full-length normal human P
      cDNA resulted in complementation of deficient melanin biosynthesis and
      hypopigmentation. In contrast, transfection with mutant human P cDNAs containing
      amino acid substitutions (A481T, V443I) found in patients with OCA2 resulted in
      minimal or partial correction, consistent with the corresponding pigmentation
      phenotypes in patients with these mutations. These results demonstrate the
      utility of this model system for distinguishing true OCA2 mutations from
      nonpathologic polymorphisms and for quantitating the effect of these mutations on
      P function.

PMID- 8980284
TI  - Interleukin-1beta-induced inhibition of hair growth in vitro is mediated by
      cyclic AMP.
AB  - Interleukin (IL)-1 has been shown to be a potent inhibitor of hair growth in
      vitro. We hypothesized that this cytokine might be a decisive factor causing hair
      loss during the lymphocytic attack in alopecia areata. Neither the intracellular
      pathways involved in hair growth inhibition mediated by IL-1beta nor the signal
      transduction processes within hair follicles in general are known. We therefore
      investigated the intracellular signals involved in human hair growth in vitro.
      Hair follicles were isolated from scalp biopsies by microdissection, and hair
      growth was measured daily by image analysis. We assessed intracellular signal
      transducing elements using specific inhibitors or activators either alone or in
      combination with IL-1beta. The calcium ionophore A 23187 induced a rapid and
      complete arrest of hair growth, and phorbol-12-myristate-13-acetate (PMA),
      genistein, or IL-1beta decreased hair growth by approximately 60%-80%. IL-1beta
      elicited hair growth arrest was not antagonized by calphostin C, a specific
      inhibitor of protein kinase C. In contrast, coincubation of IL-1beta with
      pertussis toxin or H 1004 neutralized the effect of IL-1beta, and dibutyryl-cAMP
      and cholera toxin, an activator of adenylate cyclase, inhibited hair growth.
      These data suggest that cAMP acts as a second messenger for IL-1beta-induced
      inhibition of hair growth. Moreover, our data indicate that in vitro hair growth
      is dependent on intracellular Ca2+ levels and activation of tyrosine kinase as
      well as protein kinase C. We were unable to detect a signal transducing element
      responsible for enhanced hair growth in vitro.

PMID- 8980285
TI  - Calcitonin gene-related peptide inhibits proliferation and antigen presentation
      by human peripheral blood mononuclear cells: effects on B7, interleukin 10, and
      interleukin 12.
AB  - CGRP is a neuropeptide that has previously been described to possess
      immunosuppressive activities. CGRP is released from peripheral nerves that, in
      the skin, are in close physical association with dendritic APC. We sought to
      investigate the mechanisms by which CGRP can inhibit immune responses by studying
      its effects on human peripheral blood mononuclear cells (PBMC). Using allogeneic
      monocytes as stimulator cells, CGRP could inhibit the proliferation of PBMC by
      47% when CGRP was present for the duration of culture. Interestingly, when the
      stimulator monocytes were incubated with CGRP for 2 h prior to irradiation then
      washed, the observed inhibition increased to 85%, suggesting that CGRP was
      exerting a direct effect on the monocyte stimulator population. Finally, the
      recall response to tetanus toxoid (TT) by PBMC from individuals vaccinated with
      TT 14 d prior was inhibited by 25-50% in the presence of CGRP. Also, CGRP
      decreased the levels of B7.2 but not B7.1 on treated monocytes, and this
      inhibition could be abrogated by the addition of anti-IL-10 antibody, suggesting
      that the inhibition was mediated by an increase in IL-10 production. Moreover,
      increased IL-10 production was confirmed by ELISA. Both IL-12 p40 and IFN-gamma
      levels in CGRP-treated cultures were found to be decreased by approximately 30%.
      The decrease in IL-12 p40 levels could be reversed by addition of anti-IL-10.
      These data suggest that CGRP inhibits PBMC proliferation, in part, through the
      release of IL-10, which in turn can downregulate important co-stimulatory
      molecules and the cytokines IL-12 and IFN-gamma.

PMID- 8980286
TI  - CD45 molecule in gammadelta T-cell generation: disruption of CD45 exon 6 does not
      affect Vgamma3 dendritic epidermal T-cell development.
AB  - There are two distinct lineages of T cells: T-cell receptor (TCR) alphabeta
      bearing cells (alphabeta T cells) and TCR gammadelta-bearing cells (gammadelta T
      cells). All of the alphabeta T cells and most subsets of gammadelta T cells
      develop in the thymus. It has been demonstrated that the protein tyrosine
      phosphatase CD45 plays a pivotal role in the intrathymic development of alphabeta
      T cells. Thymocyte maturation is arrested at the transitional stage from immature
      CD4+ CD8+ double-positive to mature CD4+ or CD8+ single-positive cells after CD45
      exon 6 gene disruption. In this study, we examined whether Vgamma3 dendritic
      epidermal T cells (DETC), a subset of thymus-dependent gammadelta T cells
      uniquely residing in the murine epidermis, are altered in the CD45 exon 6
      deficient mice. In situ immunolabeling on epidermal sheets demonstrated that the
      CD45-deficient mice had a normal density and immunophenotype of Vgamma3 DETC
      compared with the wild-type control mice. Reverse transcriptase polymerase chain
      reaction revealed that similar levels of Vgamma3 TCR mRNA were present in the
      epidermis of CD45-deficient mice and wild-type controls. Flow cytometry
      demonstrated no significant difference in the proportion of Vgamma3 T cells in
      the epidermis between the genotypes. In addition, Vgamma2 T cells, another subset
      of gammadelta T cells, were also examined by flow cytometry. The frequency of
      Vgamma2 T cells in lymph nodes was normal in the CD45-deficient mice. Our results
      indicate that although CD45 is crucial for the development of alphabeta T cells,
      this molecule is not necessary for the thymic maturation of gammadelta T cells,
      including Vgamma3 DETC and Vgamma2 T cells.

PMID- 8980287
TI  - Human papillomavirus DNA in non-melanoma skin cancers of a renal transplant
      recipient: detection of a new sequence related to epidermodysplasia verruciformis
      associated types.
AB  - The detection of human papillomavirus (HPV) types originally isolated from
      patients with epidermodysplasia verruciformis (EV) in skin tumors of transplant
      recipients may point to a role of this HPV subgroup in non-melanoma skin cancer
      in immunosuppressed people. We analyzed 17 formalin-fixed, paraffin-embedded
      biopsies of benign or malignant skin tumors of a renal transplant patient with
      unusually widespread cutaneous carcinomas. Using a nested polymerase chain
      reaction (PCR), HPV-specific DNA was demonstrated in 11 specimens (65%). Analysis
      of nine PCR amplification products revealed four different sequences related to
      EV-associated HPVs. Three sequences occurred only in one lesion. In six samples
      identical sequences were found that differed from all HPV sequences published to
      date and may therefore represent a novel EV-HPV type, preliminarily labeled
      RTRX7. RTRX7 was found in benign, premalignant, and malignant skin lesions.
      Alignments identified HPV12 as the closest relative of RTRX7, both in the DNA
      (81% homology) and in the amino acid sequence (84% homology).

PMID- 8980288
TI  - Modulation of fatty acid oxidation alters contact hypersensitivity to urushiols:
      role of aliphatic chain beta-oxidation in processing and activation of urushiols.
AB  - Lithraea caustica, or litre, a tree of the Anacardiaceae family that is endemic
      to the central region of Chile, induces a severe contact dermatitis in
      susceptible human beings. The allergen was previously isolated and characterized
      as a 3-(pentadecyl-10-enyl) catechol, a molecule belonging to the urushiol group
      of allergens isolated from poison ivy and poison oak plants. Because urushiols
      are pro-electrophilic haptens, it is believed that the reactive species are
      generated intracellularly by skin keratinocytes and Langerhans cells. The active
      species are presumed to modify self proteins which, after proteolytic processing,
      would generate immunogenic peptides carrying the hapten. The presence of a 15
      carbon-length hydrophobic chain should impair antigen presentation of self
      modified peptides by class I MHC molecules, either by steric hindrance or by
      limiting their sorting to the ER lumen. We have proposed that the shortening of
      the aliphatic chain by beta-oxidation within peroxisomes and/or mitochondria
      should be a requirement for the antigen presentation process. To test this
      hypothesis we investigated the effect of drugs that modify the fatty acid
      metabolism on urushiol-induced contact dermatitis in mice. Clofibrate, a
      peroxisomal proliferator in mice, increased the immune response to the urushiols
      from litre by 50%. Conversely, tetradecyl glycidic acid, an inhibitor of the
      uptake of fatty acids by mitochondria, decreased the hypersensitivity to the
      hapten. An increase in the level in glutathione by treatment of the animals with
      2-oxotiazolidin-4-carboxilic acid lowered the response. Those findings strongly
      support a role for the fatty acid oxidative metabolism in the processing and
      activation of urushiols in vivo.

PMID- 8980289
TI  - C3 production of cultured human epidermal keratinocytes is enhanced by IFNgamma
      and TNFalpha through different pathways.
AB  - We investigated the regulation of C3 production by human cultured epidermal
      keratinocytes by enzyme-linked immunosorbent assay. The results showed that
      IFNgamma and TNFalpha enhanced the synthesis of C3 by epidermal keratinocytes in
      a concentration-dependent manner. Moreover, a protein kinase C (PKC) inhibitor
      blocked C3 production, whereas PMA enhanced it. There was a synergistic effect
      between IFNgamma and TNFalpha. In experiments to investigate the role of protein
      tyrosine kinase (PTK) in C3 production, we found that treatment with herbimycin
      A, a specific inhibitor for the c-Src-related PTK, caused significant enhancement
      of the C3 production induced by IFNgamma or TNFalpha, suggesting that c-Src-type
      PTK(s) provides a negative signal to C3 production. Each competitive inhibitor of
      PTK, genistein or tyrphostin, substantially increased the C3 production by
      IFNgamma at lower concentrations, although each agent had little effect on
      TNFalpha-associated production of C3 at the same concentrations. The data show
      that pro-inflammatory cytokines IFNgamma and TNFalpha synergistically augment C3
      production by epidermal keratinocytes by different pathways.

PMID- 8980290
TI  - Development of an ELISA for rapid detection of anti-type VII collagen
      autoantibodies in epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is an acquired blistering skin disease
      characterized by the presence of IgG autoantibodies to type VII collagen. EBA
      autoantibodies recognize four major immunodominant epitopes localized within the
      amino-terminal, noncollagenous (NC1) domain. In this study, we developed a rapid,
      quantitative enzyme-linked immunosorbent assay (ELISA) to detect autoantibody
      activity against the complete NC1 domain of type VII collagen with the use of an
      eukaryotic-expressed, recombinant human NC1 antigen. With the ELISA, we tested
      serum from patients with EBA (n = 24), bullous systemic lupus erythematosus
      (BSLE) (n = 3), bullous pemphigoid (n = 16), pemphigus (n = 11), and normal
      controls (n = 12). All EBA and BSLE serum, including four sera that were negative
      by indirect immunofluorescence, demonstrated reactivity with immobilized NC1 in
      the ELISA. In contrast, none of the sera from healthy control subjects or
      patients with unrelated blistering skin diseases reacted with NC1. The EBA sera
      also reacted with recombinant NC1 by immunoblot analysis but with less
      sensitivity. Thus, the newly developed ELISA using recombinant NC1 is a
      sensitive, specific assay and a useful tool for rapidly screening EBA and BSLE
      serum.

PMID- 8980292
TI  - HaCaT cell line as a model system for vitamin D3 metabolism in human skin.
AB  - Synthesis and catabolism of calcitriol (1,25(OH)2D3) were studied using HaCaT
      cell line as a cell culture model. Our results indicate that stimulation of HaCaT
      cells with epidermal growth factor (EGF) or transforming growth factor-alpha (TGF
      alpha) within 16 h just prior to reaching confluence amplified the production of
      calcitriol when calcidiol (3H-25OHD3) was used as a substrate. EGF- and TGF-alpha
      induced (0.1-10 nM) 1-hydroxylation of 3H-25OHD3 was concentration-dependent but
      showed different kinetics. Synthesis of calcitriol induced by EGF was inversely
      related to the degree of cellular confluence. Stimulation by EGF was an
      actinomycin D- and cycloheximide-sensitive process. Independently of the growth
      factor used, the production of 3H-24R,25(OH)2D3 and the catabolism of 3H
      1,25(OH)2D3 to 3H-1,24,25(OH)3D3 were unexpectedly low (< or = 5% and < or =
      2%/), as compared to the amount of calcitriol generated. Exogenous addition of
      unlabeled 1,25(OH)2D3, 1,24R(OH)2D3, calcipotriol, or 24R,25(OH)2D3 at
      concentrations as low as 10(-11) M, potently inhibited the 3H-1,25(OH)2D3
      production. These results suggest that EGF-treated HaCaT keratinocytes could
      serve for further studies of the vitamin D3 pathway and its relationship to
      proliferation and differentiation, but differences in calcitriol synthesis and
      catabolism from those in cultured primary keratinocytes or other cell lines must
      be considered.

PMID- 8980291
TI  - Amphiregulin and nerve growth factor expression are regulated by barrier status
      in murine epidermis.
AB  - Disruption of the murine permeability barrier by solvents or tape stripping
      stimulates a homeostatic repair response that includes increased epidermal DNA
      synthesis. To identify potential mediators of the increase in DNA synthesis, we
      have measured epidermal levels of mRNAs encoding various growth factors after
      acute barrier disruption. In this study, mRNAs for amphiregulin and nerve growth
      factor were each shown to increase over controls at 30 min, reach peak levels of
      12- to 30-fold at 1-2 h, and return to control levels by 6 h after tape
      stripping. A similar time course for the increase of amphiregulin and nerve
      growth factor mRNAs was observed after an unrelated form of barrier disruption,
      i.e., acetone treatment. Furthermore, artificial restoration of the barrier by
      Latex occlusion, immediately following barrier disruption by acetone treatment,
      inhibited the increase in epidermal amphiregulin and nerve growth factor mRNA
      levels, indicating that barrier status regulates the production of these growth
      factors. In contrast, mRNA levels of transforming growth factor-beta1, an
      inhibitory growth factor, were unchanged at early times and decreased by 53% (p <
      0.02) 6 h after tape stripping, whereas mRNA levels of transforming growth factor
      alpha remained unchanged at all times after acute barrier disruption. These
      results suggest that barrier disruption stimulates the expression of amphiregulin
      and nerve growth factor. Together, these regulators of keratinocyte growth and
      differentiation may be responsible for the increased proliferative response that
      is associated with barrier disruption.

PMID- 8980293
TI  - Localization of aminopeptidase activity in freshly excised human skin: direct
      visualization by confocal laser scanning microscopy.
AB  - The aim of this study was to localize and visualize aminopeptidase activity
      within freshly excised, dermatomed human skin without perturbation of its
      histologic integrity. The use of confocal laser scanning microscopy (CLSM) is
      introduced as a novel approach by which to monitor the degradation of suitable
      substrates in the skin. The fluorescence of the metabolites originating from the
      cleavage of the aminopeptidase probe bis-Leu-rhodamine 110 (Leu2-R11O) was
      interpreted to reflect the local aminopeptidase activity in the tissue. To
      separate the kinetics of diffusion and degradation of Leu2-R110, a lateral
      application mode was introduced: the probe was applied at the cutting plane of a
      mechanical cross-section of the sample, and optical cross-sections were made
      parallel to the cutting plane of the mechanical section. By this means,
      simultaneous and equal access of the substrate to the various strata and domains
      of the skin was achieved. The observations revealed that the fluorescence, i.e.,
      aminopeptidase activity, was evenly distributed throughout the viable part of the
      epidermis, with enhanced fluorescence ("hot spots") in the upper layers of the
      stratum granulosum, while dermis and stratum corneum showed considerably less
      aminopeptidase activity. Independent studies with hair follicles (obtained from
      trypsin-separated stratum corneum) also showed aminopeptidase activity, mostly at
      the root sheath. Because of the advantage of direct visualization and
      localization of enzymatic activity in intact tissue, the lateral application mode
      of substrate administration in combination with CLSM may be beneficial to further
      elucidate the location and intensity of metabolic activity in other living
      tissues as well.

PMID- 8980294
TI  - Iontophoretic delivery of ALA provides a quantitative model for ALA
      pharmacokinetics and PpIX phototoxicity in human skin.
AB  - Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) is
      increasingly employed for skin cancer, yet ALA dosing is crude. Using
      iontophoresis, we developed a rapid and quantifiable system for topical ALA
      delivery, with measurement of subsequent PpIX fluorescence and phototoxicity. ALA
      was iontophoresed from a 2% solution into upper inner arm skin of 13 healthy
      volunteers. Six doses of ALA were delivered with a series of charges varying from
      3-120 milliCoulombs (mC); four additional doses were given with a charge of 60
      mC. Five hours post-iontophoresis, sites were irradiated with broad-band yellow
      red light, the series of six ALA doses receiving 100 J/cm2, while the four
      identical doses received 6.25, 12.5, 25, and 50 J/cm2, respectively. Resultant
      erythema was measured by reflectance spectroscopy. The time course of PpIX
      fluorescence was ALA-dose-dependent. With charge < or = 24 mC, PpIX fluorescence
      peaked at 3 h and returned to zero at 9-10 h, whereas charges > 24 mC had a
      sustained peak at 5-10 h, falling to zero by 24 h. Pre-irradiation, PpIX
      fluorescence correlated with ALA dose (r = 1.0). PpIX fluorescence fell
      immediately post-irradiation (p < 0.0001); recovery levels at 3 h correlated with
      ALA dose (p < 0.0001). Delayed erythema correlated with ALA dose and irradiation
      dose (p < 0.0001, p < 0.01, respectively). Both PpIX fluorescence intensity pre
      irradiation and fall in PpIX fluorescence post-irradiation correlated with
      erythema (r = 0.98). Hence, PpIX synthesis is ALA-dose-dependent, and
      phototoxicity can be predicted from ALA dose, irradiation dose, and
      photobleaching of PpIX. This reproducible system allows accurate dosimetry in
      topical PDT and facilitates study of ALA metabolism.

PMID- 8980296
TI  - Activation of ribosomal protein S6 kinase in psoriatic lesions and cultured human
      keratinocytes by epidermal growth factor receptor ligands.
AB  - p70 Ribosomal protein S6 kinase is a critical down-stream effector of a mitogen
      stimulated signaling pathway that is selectively inhibited by the
      immunosuppressant rapamycin. The purpose of this study was to quantify S6 kinase
      expression in psoriatic involved, uninvolved, and normal epidermis and to
      characterize regulation of S6 kinase activity in cultured normal human
      keratinocytes. S6 kinase activity was increased 4-fold in psoriatic lesions (1.63
      +/- 0.25 pmol per min per mg, n = 6), compared to nonlesional (0.44 +/- 0.12 pmol
      per min per mg, n = 6, p < 0.01), and normal (0.35 +/- 0.14 pmol per min per mg,
      n = 7, p < 0.01) epidermis. In contrast, S6 kinase mRNA and protein levels were
      not significantly different among psoriatic lesional, nonlesional, and normal
      epidermis. In keratinocytes, S6 kinase activity was stimulated 3-fold by
      mitogenic epidermal growth factor (EGF) receptor ligands, EGF and transforming
      growth factor-alpha (TGF-alpha), but not by cytokines interleukin-1alpha, tumor
      necrosis factor-alpha, interferon-gamma, or transforming growth factor-beta1. TGF
      alpha stimulation of S6 kinase activity was inhibited in a concentration
      dependent manner by rapamycin (IC50 < 0.2 nM) and the specific EGF receptor
      antagonist PD153035 (IC50 = 20 nM). Rapamycin also inhibited EGF-stimulated
      proliferation of keratinocytes (IC50 = 0.2 ng per ml) with a potency similar to
      that reported for inhibition of T-cell proliferation. We conclude: (i) the
      mitogenic signaling pathway(s) regulating S6 kinase is activated in psoriatic
      lesions, thus accounting for increased S6 kinase activity in the absence of
      increased S6 kinase gene or protein expression; (ii) S6 kinase activation in
      lesional keratinocytes likely occurs in response to EGF receptor stimulation by
      TGF-alpha and/or amphiregulin, which are known to be elevated in psoriatic
      lesions; and (iii) keratinocyte as well as T-cell mitogenic signaling pathways
      are susceptible to inhibition by rapamycin, suggesting that rapamycin may be of
      therapeutic benefit in the treatment of psoriasis.

PMID- 8980295
TI  - Molecular subtyping of Borrelia burgdorferi sensu lato isolates from five
      patients with solitary lymphocytoma.
AB  - Solitary lymphocytoma is a rare cutaneous manifestation of Lyme borreliosis that
      has been reported almost exclusively from Europe. This suggests that its
      etiologic agent may be absent or extremely rare on the North American continent.
      All three species of B. burgdorferi sensu lato known to be associated with human
      Lyme borreliosis (B. burgdorferi sensu stricto, B. garinii, and B. afzelii have
      been isolated in Europe, whereas only B. burgdorferi sensu stricto has been found
      in North America. This suggests that either B. garinii or B. afzelii might be the
      etiologic agent of borrelial lymphocytoma. To investigate this hypothesis we
      characterized five strains of B. burgdorferi sensu lato isolated from
      lymphocytoma lesions of patients residing in Slovenia. The methods used included:
      large restriction fragment pattern analysis of restriction enzyme MluI-digested
      genomic DNA, plasmid profiling, protein profiling, ribotyping using 5S, 16S, and
      23S rDNA probes, and polymerase chain reaction amplification of the rrf (5S)-rrl
      (23S) intergenic spacer region. Molecular subtyping showed that four of the five
      isolates belonged to the species B. afzelii; however, this species is the
      predominant patient isolate in Slovenia and, therefore, may not represent a
      preferential association with lymphocytoma. The fifth isolate appeared to be most
      closely related to the DN127 genomic group of organisms. Further characterization
      of the isolate revealed that it possessed a unique molecular "fingerprint." The
      results not only show that borrelial lymphocytoma can be caused by B. afzelii but
      also demonstrate an association with another genomic group of B. burgdorferi
      sensu lato that is present in North America as well.

PMID- 8980297
TI  - Convergent and discriminant validity of a generic and a disease-specific
      instrument to measure quality of life in patients with skin disease.
AB  - Skindex is a quality-of-life instrument for skin diseases. To determine its
      convergent validity and its advantage relative to a generic measure, we compared
      responses of 132 dermatology patients to Skindex and the Medical Outcomes Study
      36-item Short-Form Survey (SF-36). We hypothesized that (i) correlations between
      similar scales would be strong but not redundant (r = 0.5-0.6), and (ii) Skindex
      scores would correlate more highly with responses about skin disease-related
      aspects of health, and SF-36 scores would correlate more highly with responses
      concerning general health. As measured by the SF-36, patients reported general
      health status similar to the normal population, and SF-36 scores did not
      correlate with dermatologists' judgments about the severity of skin disease.
      Correlations between the same scales of the two instruments were as hypothesized
      (range of r, 0.44-0.56), and patients with low, medium, or high responses to
      Skindex differed similarly in SF-36 scores. On the other hand, some patients who
      reported on the SF-36 that they were free of physical symptoms (37% of patients)
      or social effects (54%) on Skindex, reported such effects from their skin
      disease. Also, responses about skin-related health aspects correlated more highly
      with Skindex than SF-36 (for skin condition, mean r = 0.42 vs 0.28; for
      disfigurement, 0.38 vs 0.24). Conversely, responses concerning general health
      correlated more highly with SF-36 than Skindex (for self-reported health status,
      mean r = 0.28 vs 0.16; for co-morbidity, 0.48 vs 0.37). This study further
      supports the validity of Skindex and also suggests that both generic and disease
      specific health status measures can contribute to the assessment of patients with
      skin diseases.

PMID- 8980298
TI  - Chemotactic 5-oxo-eicosatetraenoic acids induce oxygen radical production, Ca2+
      mobilization, and actin reorganization in human eosinophils via a pertussis toxin
      sensitive G-protein.
AB  - The arachidonic acid metabolites 5-oxo-[6E,8Z,11Z,14Z]-eicosatetraen oic acid
      (5oETE) and 5-oxo-15-hydroxy-[6E,8Z,11Z,13E]-eicosatetrae noi c acid (5oHETE) are
      potent eosinophil chemotaxins. Here, the activation profile of 5-oxo-eicosanoids
      in eosinophils was further characterized and compared to other eosinophil
      activators such as complement fragment C5a (C5a), platelet-activating factor
      (PAF), interleukin-5 (IL-5), and phorbol ester (PMA). Flow cytometric studies
      revealed a rapid and transient actin polymerization upon stimulation by both 5
      oxo-eicosanoids. Desensitization studies using actin polymerization as the
      parameter indicated cross-desensitization between the two 5-oxo-eicosanoids but
      revealed no interference with the response to other chemotaxins. Fluorescence
      measurements with Fura-2-labeled eosinophils in the presence of EGTA indicated
      Ca2+-mobilization from intracellular stores by 5oETE and 5oHETE. Both 5-oxo
      eicosanoids stimulated the production of reactive oxygen metabolites as
      demonstrated by lucigenin-dependent chemiluminescence, superoxide dismutase
      inhibitable cytochrome C reduction, and flow cytometric dihydrorhodamine-123
      analysis. At optimal concentrations the changes induced by 5-oxo-eicosanoids were
      comparable to those obtained by C5a and PAF, whereas IL-5 and PMA induced only a
      restricted pattern of cell responses. Cell responses elicited by 5-oxo
      eicosanoids were inhibited by pertussis toxin, indicating coupling of the
      putative 5-oxo-eicosanoid-receptor to G-proteins. These results indicate that 5
      oxo-eicosanoids are stong activators of eosinophils with comparable biologic
      activity to the eosinophil chemotaxins C5a and PAF. These findings point to a
      role of 5-oxo-eicosanoids in the pathogenesis of eosinophilic inflammation as
      chemotaxins as well as activators of pro-inflammatory activities.

PMID- 8980299
TI  - Telomerase activity concentrates in the mitotically active segments of human hair
      follicles.
AB  - Telomerase is a ribonucleoprotein enzyme capable of adding hexanucleotide repeats
      onto the ends of linear chromosomal DNA. Whereas normal somatic cells with a
      limited replicative capacity fail to express telomerase activity, most immortal
      eukaryotic cells do. Cells of renewal tissues (e.g., skin, intestine, blood)
      require an extensive proliferative capacity. Some cells in such renewal tissues
      also express telomerase activity, most likely to prevent rapid erosion of their
      telomeres during cell proliferation. In this study, we measured the levels of
      telomerase activity in dissected compartments of the human hair follicle: hair
      shaft, gland-containing fragment, upper intermediate fragment (where it is
      thought undifferentiated stem cells reside), lower intermediate fragment, and in
      the bulb-containing fragment (an area with high mitotic activity containing a
      more differentiated pool of keratinocytes). In anagen follicles, high levels of
      telomerase activity were found almost exclusively in the bulb-containing fragment
      of the follicles, with low levels of telomerase in the bulge area (intermediate
      fragments) and gland-containing fragment. In comparison, catagen follicles had
      low levels of telomerase activity in the bulb-containing fragments as well as in
      other compartments. Such observations indicate that, in anagen hair follicles,
      the fragments containing cells actively dividing (e.g., transient amplifying
      cells) express telomerase activity, whereas fragments containing cells with low
      mitotic activity, for example, quiescent stem cells, express low levels of
      telomerase activity.

PMID- 8980300
TI  - Human herpesvirus-8 DNA sequences in a patient with pemphigus vulgaris, but
      without HIV infection or Kaposi's sarcoma.

PMID- 8980301
TI  - Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 is not detectable in
      peripheral blood mononuclear cells of the relatives of sporadic KS patients.

PMID- 8980302
TI  - Diacylglycerol-induced tanning.

PMID- 8980303
TI  - Cycle-time and residence-time density approximations in a stochastic model for
      circulatory transport.
AB  - The concentration of a drug in the circulatory system is studied under two
      different elimination strategies. The first strategy--geometric elimination--is
      the classical one which assumes a constant elimination rate per cycle. The second
      strategy--Poisson elimination--assumes that the elimination rate changes during
      the process of elimination. The problem studied here is to find a relationship
      between the residence-time distribution and the cycle-time distribution for a
      given rule of elimination. While the presented model gives this relationship in
      terms of Laplace-Stieltjes transform., the aim here is to determine the shapes of
      the corresponding probability density functions. From experimental data, we
      expect positively skewed, gamma-like distributions for the residence time of the
      drug in the body. Also, as some elimination parameter in the model approaches a
      limit, the exponential distribution often arises. Therefore, we use Laguerre
      series expansions, which yield a parsimonious approximation of positively skewed
      probability densities that are close to a gamma distribution. The coefficients in
      the expansion are determined by the central moments, which can be obtained from
      experimental data or as a consequence of theoretical assumptions. The examples
      presented show that gamma-like densities arise for a diverse set of cycle-time
      distribution and under both elimination rules.

PMID- 8980304
TI  - A mathematical model for intracellular effects of toxins on DNA adduction and
      repair.
AB  - The process by which certain classes of toxins compounds or their metabolites may
      react with DNA to alter the genetic information contained in subsequent
      generations of cells or organisms are a major component of hazard associated with
      exposure to chemicals in the environment. Many classes of chemicals may form DNA
      adducts and there may or may not be a defined mechanism to remove a particular
      adduct from DNA independent of replication. Many compounds and metabolites that
      bind DNA also readily bind existing proteins; some classes of toxins and DNA
      adducts have the capacity to inactivate a repair enzyme and divert the repair
      process competitively. This paper formulates an intracellular dynamic model for
      one aspect of the action of toxins that form DNA adducts, recognizing a capacity
      for removal of those adducts by a repair enzyme combined with reaction of the
      toxin and/or the DNA adduct to inactivate the repair enzyme. This paper model
      illustrates the possible saturation of repair enzyme capacity by the toxin dosage
      and shows that bistable behavior can occur, with the potential to induce abrupt
      shifts away from steady state equilibria. The model suggests that bistable
      behavior, dose and variation between individuals or tissues may combine under
      certain conditions to amplify the biological effect of dose observed as DNA
      adduction and its consequences as mutation. A model recognizing stochastic
      phenomena also indicates that variation in within-cell toxin concentration may
      promote jumps between stable equilibria.

PMID- 8980305
TI  - Isologous diversification: a theory of cell differentiation.
AB  - An isologous diversification theory for cell differentiation is processed, based
      on simulations of interacting cells with biochemical networks and the cell
      division process following consumption of some chemicals. According to the
      simulations of the interaction-based dynamical systems model, the following
      scenario of the cell differentiation is proposed. (1) Up to some threshold
      number, divisions bring about almost identical cells with synchronized
      biochemical oscillations. (2) As the number is increased, the oscillations lose
      synchrony, leading to groups of cells with different phases of oscillations. (3)
      Amplitudes of oscillation and averaged chemical compositions start to differ by
      groups of cells. The differentiated behavior of states is transmitted to daughter
      cells. (4) Recursivity is formed so that the daughter cells keep the identical
      chemical character. This "memory" is made possible through the transfer of
      initial conditions. (5) Successive differentiation proceeds. The mechanism of
      tumor cell formation, origin of stem cells, anomalous differentiation by
      transplantations, apoptosis and other features of cell differentiation process
      are also discussed, with some novel predictions.

PMID- 8980306
TI  - "A socioeconomic assessment of human exposure to ozone in the South Coast Air
      Basin," (Journal of the Air & Waste Management Association, Vol. 46, June 1996,
      pp. 547-557), by Marcelo E. Korc, Sonoma Technology, Inc.

PMID- 8980307
TI  - "Air emissions from the manufacture of printing inks," (Journal of the Air &
      Waste Management Association, Vol. 46, July 1996, pp. 683-685), by J.B. Phillips,
      G.R. Mysore, J.F. Griffiths, and R.V. Bailey, Engineering Development Institute.

PMID- 8980308
TI  - "Air emissions from the manufacture of printing inks," (Journal of the Air &
      Waste Management Association, Vol. 46, July 1996, pp. 683-685), by J.B Phillips,
      G.R. Mysore, J.F. Griffiths, and R.V. Bailey, Engineering Development Institute.

PMID- 8980309
TI  - Public health. We're getting better all the time.

PMID- 8980310
TI  - Quality watch ... consumers are more concerned about the cost of their health
      care than they are about its quality.

PMID- 8980311
TI  - Managed care. Health plans that please.

PMID- 8980312
TI  - Technology ... battery-powered left ventricular-assist device.

PMID- 8980313
TI  - Integration ... hospitals may be losing their appetite for physician practices,
      but integrated delivery systems are still hungry for them.

PMID- 8980314
TI  - Deals that went down the drain.
AB  - What's that sound you hear? It's another merger going down the drain. Most
      mergers begin with great fanfare over cutting costs and eliminating overlapping
      services, but many end with a terse press release saying only that the party's
      over. Here's how even the best deals can go bad.

PMID- 8980315
TI  - Twice bitten. Election commentary.
AB  - You might expect a reelected President Clinton and the Republican Congress to
      approach health care legislation like a postman who's been bitten by a dog-very
      carefully. But waiting isn't an option, not with Medicare woes unsolved. Will
      bipartisanship prevail?

PMID- 8980316
TI  - Being there.

PMID- 8980317
TI  - Getting the picture.
AB  - Imaging's costly reputation isn't an entirely accurate picture. Sure, the latest
      equipment is still pricey, but competition and business savvy are teaming up to
      give the marketplace what it wants: lower costs without scrimping on quality.
      It's an economic makeover.

PMID- 8980318
TI  - Crisis control. A surefire merger.

PMID- 8980319
TI  - Rules & regs. Safety in numbers.

PMID- 8980320
TI  - Health reform. Kaiser goes globe-trotting.

PMID- 8980321
TI  - Quality patrol. A cutting cost analysis of hysterectomies.

PMID- 8980322
TI  - Executive advancement ... health care's millionaire club.

PMID- 8980323
TI  - Finance ... give small-town and rural hospitals their due.

PMID- 8980324
TI  - Managed care ... Medicare's 4 million HMO members can demand hearings if they are
      refused medical services.

PMID- 8980325
TI  - Finance. Bills that baffle.

PMID- 8980326
TI  - Managed care. HMOs have less fat to cut.

PMID- 8980327
TI  - Insurance. Seeing red about not being Blue.

PMID- 8980328
TI  - Physicians ... specialists, brace yourselves for more future shock.

PMID- 8980329
TI  - Continuum of care ... the care of those with mental and behavioral disorders is
      being managed more aggressively.

PMID- 8980330
TI  - Team spirit. Interview by Terese Hudson.

PMID- 8980331
TI  - Senior bashing.
AB  - ?Elderly, affluent--and selfish.? That New York Times headline could be the
      battle cry of a group of politicians, policy wonks and journalists. They charge
      that seniors receive an unfair share of federal spending through Medicare,
      Medicaid and Social Security. But what's the myth and what's reality?

PMID- 8980332
TI  - Anxious in Albuquerque.

PMID- 8980333
TI  - Think big!

PMID- 8980334
TI  - The cost of keeping up.

PMID- 8980335
TI  - Head for business.
AB  - No matter how you look at it, "the business of nursing remains patient care,"
      writes Marjorie Beyers in her preface to The Business of Nursing, a recent book
      from American Hospital Publishing. Still, in the book with potential authors and
      reviewers, the idea of putting the word "business" in front of "nursing" raised a
      few eyebrows, says Beyers, executive director of the American Association of
      Nurse Executives. "In corporate thinking, any service of value has a price.
      Although certainly nurse executives agree that nursing care is a valued human
      science, there is lively debate about whether it should have a price." To that
      end, the book's six essays reflect the complexity of changes in health care, the
      effects on patients and their families, and the challenges facing nursing
      executives today. The chapter excerpted here--"Seizing Opportunities in the New
      Health Care Delivery System, " by consultant and former nursing executive Richard
      Brock--lays a foundation for changing both nursing practice and attitudes. Brock
      also offers advice for working with staff nurses to guide them through the
      changes ahead.

PMID- 8980336
TI  - Physicians. Look for the union label.

PMID- 8980337
TI  - Quality patrol. Know your neighbor's business.

PMID- 8980338
TI  - Accounting. Is your back-office a backwater?

PMID- 8980339
TI  - Hospital construction. Vegas hits a hot streak.

PMID- 8980340
TI  - Comfort care. Putting last wishes first.

PMID- 8980341
TI  - Outreach. Buy the book.

PMID- 8980342
TI  - HospitalPulse ... July 1996.

PMID- 8980343
TI  - The PT and the pendulum.

PMID- 8980344
TI  - Comprehensive review of cocaethylene and cocaine concentrations in patients.
AB  - Cocaethylene (CE) and cocaine (COC) concentrations were reviewed for 41 patients
      studied by this laboratory and found to have measurable CE in plasma. In 17
      instances, urine concentrations of CE and COC were also measured. In 15 cases
      other drugs in addition to COC and ethanol (ETOH) were detected. Thirty-three
      cases involved trauma. For the entire series, ages ranged from 19 to 48 years
      (mean 31 years) with men accounting for 36 cases. Mean concentrations were as
      follows: plasma CE, 353 nmol/L (range 16.1-1,959); plasma COC, 386 nmol/L (range
      no measurable amount-1,455); and whole-blood ETOH, 36.5 mmol/L (range no
      measurable amount-110.9). The ratio CE:COC in plasma ranged 0.1 to 4.7 (mean
      1.3). Concentrations of ETOH in whole blood showed significant negative
      correlation with plasma COC (r = -0.425, P < .01). In addition, plasma CE
      concentrations showed significant correlation with plasma COC (r = 0.422, P <
      .01). When available, urine concentrations of CE and COC showed significant
      correlation with their concentrations in plasma (r = 0.821, P < .01; and r =
      0.569, P < .05, respectively). As in plasma, urine concentrations of CE showed
      significant correlation with urine COC (r = 0.831, P < .01).

PMID- 8980345
TI  - Comparison of cardiac troponin I and lactate dehydrogenase isoenzymes for the
      late diagnosis of myocardial injury.
AB  - Cardiac troponin I (cTnI) is a highly specific marker that is elevated in the
      blood for several days following myocardial infarction. The lactate dehydrogenase
      (LD) isoenzyme 1 to isoenzyme 2 ratio (LD1/LD2) is the established marker for the
      late diagnosis of myocardial infarction. In this study, the sensitivity of
      cardiac troponin I (cTnI) and LD1/LD2 were compared as late markers of myocardial
      injury over a 5-day period in 36 patients admitted with a diagnosis of myocardial
      infarction to the coronary care unit. Over this period, the sensitivity of cTnI
      was significantly greater than that of LD1/LD2 (P < .05). The concurrent
      elevation of both cardiac markers of the five day period range from 53.1% to
      79.4%. However, this low concordance was largely due to an LD1/LD2 < 1 in the
      presence of an increased cTnI. The average discordance over the 5-day period was
      29.5%. Because cardiac troponin I (cTnI) has greater sensitivity than lactate
      dehydrogenase isoenzymes for delayed diagnosis of myocardial injury and is a more
      cost-effective test, the authors recommend it as a test of choice in this
      setting.

PMID- 8980346
TI  - Hyperhomocysteinemia. An emerging and important risk factor for thromboembolic
      and cardiovascular disease.
AB  - Homocysteine is an important contributing factor to thrombosis, vascular injury,
      and vascular disease. Mechanisms for homocysteine-induced vascular disease
      include alterations in coagulation as well as endothelial cell and vessel wall
      injury. Hyperhomocysteinemia (HH[e]) can occur when homocysteine metabolism is
      altered by mutations in enzymes responsible for homocysteine metabolism.
      Characterization of these mutations identifies patient groups at risk for
      vascular disease. Treatment of HH(e) consists of vitamins and raises the
      possibility that some forms of vascular disease may be easily, safely, and
      inexpensively treated.

PMID- 8980347
TI  - Diurnal change of blood count analytes in normal subjects.
AB  - Short-term, within one 24-hour day (diurnal period) within-person changes of the
      principal blood count analytes in healthy subjects were studied at three major
      institutions. The results from each test site were indistinguishable and were
      therefore combined to make a database of 96 healthy subjects. Analytical
      imprecision of each analyte was subtracted from the total observed variation to
      give true diurnal change. Each analyte showed characteristic changes. As would be
      expected, cellular properties of erythrocytes, such as MCV (mean cell volume) and
      MCH (mean cell hemoglobin) showed negligible change. The red cell count,
      hematocrit, and hemoglobin showed changes that were consistent with fluid balance
      change. Total white cell count and some differential count components showed
      major changes that raised questions of the confidence limits of clinical decision
      levels and the validity of commonly used reference intervals. Platelet count
      changes were typically less than analytic imprecision, suggesting the need for
      improvement in this aspect of analyzer performance.

PMID- 8980348
TI  - P53 expression in Reed-Sternberg cells does not correlate with gene mutations in
      Hodgkin's disease.
AB  - Immunohistochemically detectable p53 protein expression is common in the Reed
      Sternberg and Hodgkin's (RS-H) cells of Hodgkin's disease, but p53 gene mutations
      have only rarely been identified. The authors found p53 expression in RS-H cells
      in 16 of 30 cases of Hodgkin's disease (53%), with the percentage of RS-H
      positive cells ranging from 4% to 85%. In 12 of 30 cases (40%), at least 10% of
      the RS-H cells were positive for p53. p53 gene mutations were detected in only
      two cases (7%) using a single-stranded conformational polymorphism assay with a
      detection sensitivity of between 1% and 5%. The cellular protein, mdm-2, which
      can stabilize and functionally inactivate wild-type p53 protein, was expressed in
      RS-H cells in most of these cases (86%). However, neither case with a p53 gene
      mutation expressed mdm-2 (P < .005). The two cases with p53 gene mutations had a
      higher mean proliferative index than cases without detectable mutations (90%
      versus 72%; P < .02). p53 expression in RS-H cells may be related to concurrent
      mdm-2 protein expression and a p53-positive, mdm-2-negative immunophenotype may
      be predictive of gene mutations in RS-H cells.

PMID- 8980349
TI  - Immunophenotypic identification of Sezary cells in peripheral blood.
AB  - Despite anecdotal literature that Sezary cells express the CD4+ CD7-
      immunophenotype, no formal validation has been published establishing the use of
      this immunophenotype for clinical or experimental purposes. Consequently, the
      only method presently available for Sezary cell identification is nuclear contour
      analysis, a labor-intensive procedure not generally available at most major
      medical centers. In this study, the accuracy of CD4+ CD7- subset quantitation for
      the identification of Sezary cells was examined. The study found that the
      percentage of CD4+ CD7- cells is elevated in many Sezary syndrome/MF patients
      relative to normal, healthy individuals. In addition, CD4+ CD7- enumeration
      correlates with enumeration by nuclear contour analysis in most patients (11 of
      15) with elevated CD4/CD8 ratios. The CD4+ CD7- subset also correlates with the
      expression of other aberrant immunophenotypes, such as CD3low or CD4low. Lastly,
      CD4+ CD7- subset quantitation correlates with the number of clonal T lymphocytes,
      as measured using V beta-specific T-cell receptor monoclonal antibodies. The
      study found this method to be exceptionally accurate, with two caveats: (1) the
      absence of an expanded CD4+ CD7- subset in patients with a normal CD4/CD8 ratio
      is uninformative; and (2) in approximately 25% of patients with an elevated
      CD4/CD8 ratio, the Sezary cells are CD7+.

PMID- 8980350
TI  - Differentiation of primary and secondary cutaneous B-cell lymphoma by Southern
      blot analysis.
AB  - Malignant B-cell lymphomas represent a heterogenous group of lymphoreticular
      disorders that involve the skin in about 20% of reported cases. Skin involvement
      may be primary or secondary (ie, the result of hematogenous spread). Primary
      cutaneous B-cell lymphomas (PCBCLs) are thought to take a comparatively favorable
      course, respond readily to nonaggressive treatment, and lack evidence of
      extracutaneous spread. Nine primary B-cell lymphomas (7 centrocytic or
      centroblastic follicular, 1 immunoblastic, 1 centroblastic), three secondary
      (follicular) cutaneous B-cell lymphomas (SCBCLs) and two pseudolymphomas were
      studied. Staging revealed that bone marrow was involved only in SCBCLs.
      Centrocytes were detected in blood smear preparations of all SCBCLs. All
      lymphomas were treated with local irradiation. Patients with primary
      centroblastic and immunoblastic cutaneous lymphomas and those with secondary
      lymphomas received additional chemotherapy. Pseudolymphomas were treated by
      simple excision. Patients were monitored on average for 55 months. During this
      period, no patients with PCBCLs exhibited cutaneous relapses or hematogenous
      spread. In contrast, all patients with SCBCLs experienced cutaneous relapses.
      Peripheral blood, bone marrow, and skin samples from all patients were subjected
      to Southern blot analysis using a JH probe. Clonal rearrangement was found in all
      skin samples investigated except specimens from pseudolymphomas. Peripheral blood
      and bone marrow samples were positive in SCBCLs (the rearrangement pattern was
      different from that of the skin samples for two of the three patients), whereas
      it was negative in all PCBCLs and pseudolymphomas. In conclusion, Southern blot
      analysis of peripheral blood may be useful in differential diagnosis of PCBCLs
      and SCBCLs and a prognostic marker. Furthermore, these data confirm the
      comparatively favorable clinical course of PCBCLs and suggest that in these
      cases, local irradiation can be considered adequate treatment, whereas SCBCLs
      require additional systemic therapy.

PMID- 8980351
TI  - Sorting out mix-ups. The provenance of tissue sections may be confirmed by PCR
      using microsatellite markers.
AB  - Standard identification systems usually ensure that biopsy material is correctly
      associated with a given patient. Sometimes, as when a tumor is unexpectedly
      found, the provenance (proof of origin) of a tissue sample may be questioned; the
      tissue may have been mislabelled or contaminated with tissue from another
      patient. Techniques used to confirm tissue provenance include comparing either
      tissue markers of gender or ABO blood groups; however, these methods have weak
      confirmatory power. Recently, the use of DNA-based polymerase chain reaction
      (PCR) techniques has been reported. Paired, formalin-fixed, paraffin-embedded, 10
      microns tissue sections were selected from 17 patients, 8 of whom had carcinoma,
      either by dividing a biopsy section, using sequential biopsies, or sequential
      biopsy and autopsy tissue. The resulting 36 samples were coded before analysis.
      In two additional cases, 1-mm fragments of tumor from one patient were included
      in the tissue block of benign tissue from another patient, the tumor fragments
      were identified on hematoxylin-and-eosin-stained sections, separately scraped off
      the glass slide, and analyzed. Tissue from two clinical cases, one of suspected
      mislabelling and one with a suspected carry-over of malignant tissue were also
      investigated. Short tandem repeat sequences (STR) or microsatellites, are 2-5
      base pair repeats that vary in their repeat number between individuals. This
      variation (polymorphism) can be assessed using a PCR. A panel of markers of 3
      STRs; ACPP, INT 2, and CYP 19 (on chromosomes 3, 11, and 15, respectively) were
      used. DNA was isolated from the samples after xylene deparaffinization and
      proteinase digestion, and was then amplified in a radioactive PCR using primers
      selected to give a product size ranging from 136-178 bases. Amplified products
      were electrophoresed on denaturing polyacrylamide gels, dried, and
      autoradiographed. DNA segments were successfully extracted from all samples but
      one, which was fixed in Bouin's fluid. By comparing allele sizes from the panel,
      all tissue pairs (other than the Bouin's pair) were successfully matched, the 1
      mm tumor fragments were correctly assigned, and the two clinical problems were
      solved. STRs are highly informative and robust markers, well suited to PCR of
      small portions of tissue sections, and are an effective method to confirm the
      provenance of benign and malignant biopsy and autopsy material.

PMID- 8980352
TI  - Multinucleate giant cells in papillary thyroid carcinoma. A morphologic and
      immunohistochemical study.
AB  - Multinucleate giant cells (MGCs) occur in a variety of inflammatory,
      hyperplastic, and neoplastic thyroid disorders. They also have been recognized as
      a feature of papillary thyroid carcinoma (PTC), particularly in fine-needle
      aspiration biopsies (FNAB). However, the origin of the MGCs and their comparative
      frequencies in histologic and cytologic preparations have not been established.
      Therefore, histologic sections from 76 cases of PTC were examined and
      immunohistochemical analyses for epithelial and histiocytic markers were
      performed. Giant cells were identified in histologic sections of 35 cases (46%)
      of PTC. In cytologic preparations, MGCs were identified in 12 of 22 cases (55%).
      MGCs were present within follicles or adjacent to papillae, and were often
      associated with resorption of colloid. Immunohistochemical results indicated that
      MGCs were of histiocytic rather than epithelial origin. Multinucleate giant cells
      in PTC most likely represent a response to leakage of colloid into the
      interstitium. Although MGCs have been described most commonly in inflammatory
      conditions of the thyroid, the results of this study suggest that their presence
      should prompt a careful appraisal of associated PTC.

PMID- 8980353
TI  - Fine-needle aspiration biopsy of synovial sarcoma. A cytomorphologic analysis of
      primary, recurrent, and metastatic tumors.
AB  - Thirteen fine-needle aspiration specimens from 10 patients with histologically
      proven synovial sarcoma are described. The aspiration biopsy specimens were
      obtained from the primary tumor in five cases, locally recurrent tumors in four
      cases, pulmonary metastases in three cases, and mediastinal metastasis in one
      case. Patient's ages ranged from 22 years to 65 years; there were four women and
      six men. All cases had a confirmation biopsy and/or resection specimen that were
      reviewed. Histologic subtypes included monophasic fibrous (5 cases), monophasic
      epithelial (1 case), biphasic (3 cases), and poorly differentiated (1 case). The
      majority of the aspiration biopsy specimens were similar with moderate to marked
      smear cellularity dominated by cohesive clusters of spindle-shaped cells with
      ovoid, hyperchromatic nuclei and scanty tapering cytoplasm. Nucleoli were not
      prominent. Epithelial tumor cells with ovoid to round, mostly regular, centrally
      to eccentrically located nuclei, surrounded by scant to abundant cytoplasm
      predominated in one case (monophasic epithelial) and were admixed with spindle
      cells in a second (classical biphasic). Multi-nucleated tumor giant cells were
      not observed in any of the tumors. In biphasic synovial sarcoma, the neoplastic
      spindle cells are generally more numerous and frequent than the epithelial cells,
      making distinction from monophasic synovial sarcoma or other spindle cell soft
      tissue tumors difficult. Although synovial sarcoma may be diagnosed by fine
      needle aspiration cytology, clinical correlation, especially in monophasic types,
      is necessary to minimize errors in sarcoma classification.

PMID- 8980354
TI  - Correlation between MIB-1 staining index and the immunoreactivity of p53 protein
      in recurrent and non-recurrent meningiomas.
AB  - Wild type p53 protein has been shown by recent investigations to be involved in
      the negative regulation of cell proliferation, whereas aberrant p53 protein has
      lost this negative regulation of cell growth. Wild type p53 protein, which has a
      very short half-life, has generally been considered to be undetectable using
      immunohistochemical methods; however, according to a recent report, wild type p53
      protein may accumulate in the nuclei because of a defective ubiquitin pathway.
      Aberrant p53 protein has a longer half-life, and thus is visible using
      immunohistochemical methods. In this study, both the proliferative potential
      represented by the MIB-1 staining index (SI) and the immunoreactivity of p53
      protein in 51 intracranial meningiomas were studied applying immunohistochemical
      staining methods to archival paraffin sections. The correlation among MIB-1 SI,
      p53 immunoreactivity, histopathologic findings and the clinical course of the
      meningiomas was also analyzed retrospectively. Although it is not possible with
      available reagents to distinguish between aberrant p53 protein and wild type p53
      protein, statistical analyses show that p53 protein was immunostained both in
      meningiomas with high MIB-1 SI and in recurrent meningiomas. This demonstrates
      the close relationship among p53 immunoreactivity, MIB-1 SI, and recurrence;
      therefore, the presence of p53 protein by immunohistochemical examination may
      suggest the proliferative activity of meningioma and is capable of serving as a
      predictor of future recurrence.

PMID- 8980355
TI  - Gastric pathology in Meckel's diverticulum. Review of cases resected between 1965
      and 1995.
AB  - One hundred forty-nine case files of Meckel's diverticulum resected at our
      hospital between 1965 and 1995 were reviewed for the presence of heterotopic
      gastric mucosa. Of these, 140 cases were evaluated, and 25 demonstrated ectopic
      gastric mucosa. Six of these heterotopic tissue specimens contained no assessable
      surface mucosa; therefore only 19 were evaluated for gastric histopathologic
      changes. "Gastritis" was present in all reviewed cases, but the predominant
      pattern was that of reflux-type gastritis or gastropathy, which had not
      previously been documented at this location. This gastropathy was demonstrated in
      58% of the cases and could also account for some of the symptoms that prompted
      removal of appendixes without inflammation. Chronic and chronic active gastritis
      were also demonstrated in a minority of cases, and those with moderate or severe
      activity were associated with peptic ulceration. No Helicobacter pylori-like
      organisms were detected with either modified Giemsa stain or hematoxylin-and
      cosin (H&E) stain. Findings were inconclusive with regard to erosive gastritis
      related to nonsteroidal anti-inflammatory drugs in Meckel's diverticulum. That
      the proportion of ectopic gastric mucosa found in several studies (including this
      one) is about half that suggested in textbooks indicates a need for a better
      workup of resected Meckel's diverticulum and a search for all types of gastric
      disease if gastric heterotopia is present. Emphasis must be placed on
      identification of reflux-type chemical gastritis and gastropathy, which are often
      documented as normal mucosa.

PMID- 8980356
TI  - Calibration verification of the International Normalized Ratio.
AB  - The International Normalized Ratio (INR) system for reporting the prothrombin
      time (PT) is essentially a calibration activity intended to standardize PT
      reporting across various reagent/instrument systems. However, complete
      standardization of PT reporting through the INR has been difficult to achieve for
      a variety of reasons, including inaccurate assignment of thromboplastin
      International Sensitivity Indexes (ISIs) and specific (local) reagent/instrument
      effects. Until now, the individual laboratory has not been able to easily verify
      the accuracy of its INR. Using standard lyophilized plasmas with INR values
      assigned against IRP RBT/90 rabbit thromboplastin, the authors present a method
      that allows a laboratory to locally verify its range of accuracy for the INR. The
      method is illustrated on a single coagulometer with two thromboplastin lots of
      differing sensitivity (Pacific Hemostasis Thromboplastin-DS and Thromboplastin-D
      from rabbit sources, with respective International Sensitivity Indexes of 1.20
      and 1.97). In this illustration of the method, the accuracy of Thromboplastin-DS
      was superior to that of Thromboplastin-D. Interpretation of the data and cautions
      regarding the use of standard plasmas for calibration verification are discussed.
      Using this method, a reportable range of accuracy at a given error tolerance can
      be established locally for INR measurements within a laboratory. Laboratories of
      any size can apply this method to study the accuracy of their INR
      reagent/instrument systems, thus performing calibration verification. When used
      in conjunction with assessments of assay precision, this method can help
      laboratories to select better reagent/instrument systems and thereby produce more
      accurate and more clinically meaningful INR results.

PMID- 8980357
TI  - Cytokine induction of platelet activation.
AB  - Recent studies have focused on the accumulation of cytokines in stored platelet
      concentrates and the role that these cytokines play in mediating transfusion
      reactions. To elucidate any additional adverse effects that may be associated
      with cytokine accumulation, the authors examined whether cytokines, which
      normally accumulate during routine platelet storage, can cause platelet
      activation in vitro. Concentrations of IL-6 and IL-8 were first determined for
      random donor platelet concentrates on days 1 through 4 of storage. Fresh
      platelets were then incubated with these levels of exogenous cytokines, and
      activation measured by flow cytometry using a monoclonal antibody directed
      against p-Selectin. Significant platelet activation was observed with
      concentrations of cytokines which are normally present in days 3 and 4 of shelf
      life. The study data demonstrate that levels of cytokines that routinely
      accumulate in stored platelet products can affect platelet biology. Strategies to
      reduce cytokine generation during platelet storage may be a method to improve the
      function and viability of stored platelets used for transfusion.

PMID- 8980358
TI  - CD 30+ cutaneous lymphoma.

PMID- 8980359
TI  - The emerging role of myofibroblasts in soft tissue neoplasia.

PMID- 8980360
TI  - Immunohistochemical vs molecular biology methods. Complementary techniques for
      effective screening of p53 alterations in head and neck cancer.
AB  - The purpose of this study was to correlate p53 gene alterations and their
      expression in 85 head and neck squamous cell carcinomas. Genomic p53 was
      amplified with the polymerase chain reaction (PCR) from formalin-fixed, paraffin
      embedded tissues. Exons 5 through 8 were screened for mutations by means of non
      isotopic single-strand conformation polymorphism (SSCP) analysis. p53 expression
      was detected by means of immunohistochemistry (IHC) with the p53 monoclonal
      antibody DO-7. Twenty-three lesions (27%) showed both SSCP variants and DO-7
      immunostaining, whereas 37 (44%) demonstrated both SSCP normal patterns and
      negative staining. Twenty-five lesions (29%) were discordant, including 12 IHC
      positive (14%) and 13 SSCP-positive (15%) lesions. However, discordant IHC
      negative, SSCP-positive lesions could have been easily interpreted after
      sequencing of the abnormal samples. Had these been screened with IHC only, all
      nonsense or frameshift p53 mutations would have been missed. IHC-positive, SSCP
      negative lesions were interpreted in light of current models of p53
      immunodetection. Had these been screened with SSCP or sequencing only, a sizeable
      number of tumors expressing p53 protein abnormalities would have been undetected.
      Therefore, simultaneous use of both methods increases the number of p53
      abnormalities detected, and is warranted.

PMID- 8980361
TI  - Immunohistochemical identification of tumor markers in metastatic adenocarcinoma.
      A diagnostic adjunct in the determination of primary site.
AB  - Adenocarcinoma that metastasizes from an unknown primary site is a significant
      oncologic problem. With the exception of prostate-specific antigen and
      thyroglobulin, no single immunohistochemical marker is entirely site-specific. A
      retrospective study was undertaken to determine whether a panel of markers could
      accurately predict the site of origin of common metastatic adenocarcinomas. On
      the basis of reports of their relatively restricted specificity for carcinomas of
      colon, breast, lung, ovary, and upper gastrointestinal tract (stomach, pancreas,
      and bile duct), eight markers were selected for simultaneous evaluation: gross
      cystic disease fluid protein-15, breast cancer antigen 225 (BCA225), B72.3, DF3
      (CA15-3), carcinoembryonic antigen (CEA), CA19-9, CA125, and estrogen receptor.
      The study population consisted of 128 metastatic nonmucinous adenocarcinomas for
      which the primary site was known. Staining was performed on formalin-fixed,
      paraffin-embedded tissue using an enhanced-sensitivity avidin-biotin peroxidase
      complex detection system. The most informative markers were CEA, CA19-9, CA125,
      and BCA225. With this four-marker panel, the most predictive multiple-marker
      phenotypes, as determined by a combination of area under the receiver operating
      characteristic curve, specificity, and percent correct predictions, were CEA+,
      BCA225-, and CA125- for colon tumors; BCA225+, CEA-, and CA125- for breast
      tumors; BCA225+, CEA+, and CA19-9- for lung tumors; CA125+ and CEA- for ovarian
      tumors; and CEA+, CA19-9+, and CA125+ for upper gastrointestinal tract tumors.
      Overall, these phenotypes correctly predicted the known primary site in 66% of
      cases. Until single highly sensitive and specific markers are developed for
      adenocarcinomas other than prostate and thyroid tumors, the origin of a
      metastatic adenocarcinoma can best be suggested or excluded with
      clinicopathologic data combined with a panel of selected immunohistochemical
      markers.

PMID- 8980362
TI  - Cytologic findings in thyroid nodules after 131I treatment of hyperthyroidism.
AB  - Findings in seven cytologic specimens obtained with fine-needle aspiration biopsy
      were described in three patients in whom thyroid nodules developed after iodine
      131 treatment of hyperthyroidism. In two patients, the presence of large bizarre
      cells with hyperchromatic nuclei, coarse chromatin, and prominent nucleoli
      suggested the possibility of malignancy, and in particular, anaplastic carcinoma.
      These bizarre nuclear changes were diffuse in one patient and focal in the other.
      In the third patient, nuclei with chromatin clearing, grooves, and nuclear
      pseudoinclusions suggested papillary carcinoma. At follow-up, lesions were benign
      in all three patients. We conclude that nuclear changes suggestive of either
      anaplastic carcinoma or papillary carcinoma may be seen in thyroid nodules after
      131I treatment. Clues to the benign nature of these nodules include architectural
      arrangement of cells in cohesive clusters and flat sheets; presence of
      lymphocytes, histiocytes, colloid, cytoplasmic vacuoles, and Hurthle cells; and a
      clinical history of treatment with radioactive iodine.

PMID- 8980363
TI  - Adequate tissue sampling of prostate core needle biopsies.
AB  - Prostatic carcinoma is increasingly diagnosed on small foci of core needle biopsy
      specimens. What constitutes adequate sampling of this tissue has not been
      investigated. Two hundred twenty-nine cases were reviewed, which included 47
      cores with atypical foci, 22 with high-grade prostatic intraepithelial neoplasia
      (PIN), and 533 diagnostic of carcinoma. Six core specimens were obtained for each
      case, and two blocks were prepared containing three cores each. At least three
      slides containing multiple serial sections were prepared from each block. Ninety
      seven percent of atypical foci, 0% of high-grade PIN foci, and 25% of
      carcinomatous foci comprised less than 5% of the tissue in the core and measured
      less than 1 mm in greatest dimension. Thirteen percent of atypical foci, 0% of
      high-grade PIN foci, and 3% of carcinomatous foci were not present on the first
      slide. In every case, the tissue containing the focus was not present on the
      first slide. Thirteen percent of atypical foci and 3% of carcinomatous foci are
      not present on the first slide of prostate core needle biopsy specimens because
      the tissue containing these foci simply is not cut. As proposed in this report,
      at least three slides are necessary to detect all lesions.

PMID- 8980364
TI  - Papanicolaou smear sensitivity for adenocarcinoma in situ of the cervix. A study
      of 34 cases.
AB  - The sensitivity of cervical smears for adenocarcinoma in situ (AIS) is not known,
      nor is it known whether false-negative smears are due to sampling or to screening
      or interpretive errors. In 16 of 34 patients with AIS, 38 negative smears were
      reported 2 weeks to 7 years before biopsy. Thirty-one of these negative smears
      were rescreened, and 17 (55%) were retrospectively diagnosed as abnormal. Ten of
      the 17 had numerous well-preserved AIS cells: 5 with very small, crowded AIS
      cells, possibly originally mistaken for endometrial cells, and 5 with large
      groups in which AIS cells resembled reactive endocervical cells. Four smears were
      confirmed sampling errors. The sensitivity of cervical smears for AIS was 55% to
      72%. Improved sampling of the endocervical canal offers cytologists the
      opportunity to diagnose AIS. This study demonstrates that this opportunity may
      not be fully exploited. Small "endometrioid" AIS cells and AIS cells resembling
      reactive endocervical cells may be mistaken for benign cells, thus decreasing
      sensitivity.

PMID- 8980365
TI  - Genital angiomyofibroblastoma. Comparison with aggressive angiomyxoma and other
      myxoid neoplasms of skin and soft tissue.
AB  - Angiomyofibroblastoma (AMFB) of the genital region is a relatively recently
      described tumor of the superficial soft tissues with a marked preference for
      female patients. Three cases of AMFB were reviewed, two of which involved adult
      men. To further elucidate the pathologic features of AMFB, these three cases were
      compared with 10 cases of aggressive angiomyxoma (AA), a salient diagnostic
      alternative, and 28 cases of other myxoid tumors that may show morphologic
      similarities to these neoplasms. Conventional histologic and immunohistochemical
      features of AMFBs were compared with those of AA, myxoid leiomyoma, myxoid
      leiomyosarcoma, myxoid liposarcoma, myxoid malignant fibrous histiocytoma, myxoid
      neurofibroma, and myxoid malignant peripheral nerve sheath tumor. The
      ultrastructure of two of the three AMFBs also was analyzed. Genital AMFBs were
      circumscribed, partially myxoid proliferations that demonstrated considerable
      variation in cellular density. Neoplastic elements were bland cytologically and
      showed both fusiform and epithelioid profiles, with a tendency to concentrate
      around intralesional blood vessels. Mitotic activity and necrosis were absent,
      and the vessels assumed an arborizing configuration and were venule or capillary
      sized. In contrast, all other tumor types evaluated were infiltrative,
      cytologically atypical, or both. All AMFBs showed immunoreactivity for vimentin,
      desmin, actin, and estrogen receptor protein. These results were shared by most
      examples of AA and smooth muscle tumors as well, but were not seen in any other
      neoplasms in this study. Electron microscopic findings in cases of AMFB supported
      the presence of myofibroblastic differentiation in the tumor cells. These results
      indicate that conventional morphologic analysis is paramount in the recognition
      of genital AMFB but that immunohistology may be helpful in a limited context in
      excluding other differential diagnoses. They also support the conclusion that
      AMFB, AA, and superficial smooth muscle tumors have similar morphotypes and
      immunohistologic attributes regardless of their origin in men or women.

PMID- 8980366
TI  - Vulval angiomyofibroblastoma. Clinicopathologic analysis of six cases.
AB  - Clinicopathologic, immunohistochemical, ultrastructural, and flow cytometric
      analyses were performed on vulvar angiomyofibroblastomas in six women (ages 32 to
      46 years; average age, 41.3 years). The tumors were all well circumscribed, and
      measured 2 to 9 cm in greatest dimension. Five tumors were clinically diagnosed
      as Bartholin's gland cysts. At histologic analysis, the tumors were characterized
      by alternating hypercellular and hypocellular edematous areas with abundant blood
      vessels. The hypercellular areas showed a perivascular proliferation of spindle
      shaped and round cells, which often formed small nests or epithelioid
      arrangements, and a short fascicular pattern of spindle cells. The proliferating
      vessels were thin-walled and capillary-sized. Cellular atypia and mitotic figures
      were absent. Two tumors contained an adipose element, and one showed a prominent
      vascular proliferation reminiscent of a capillary hemangioma. At
      immunohistochemical analysis, the tumor cells were strongly positive for vimentin
      and desmin. Some cells were weakly positive for HHF35 and alpha-smooth muscle
      actin. Ultrastructurally, one neoplasm showed fibroblastic differentiation. Flow
      cytometry revealed three tumors were DNA diploid and two were aneuploid. All
      tumors were excised, and none have recurred (average follow-up, 28.3 months).
      These results indicate that angiomyofibroblastomas contain heterogeneous
      components.

PMID- 8980367
TI  - Mammary myofibroblastoma with leiomyomatous differentiation.
AB  - An unusual example of mammary myofibroblastoma in a 36-year-old woman was
      reported. The central portion resembled mammary myofibroblastoma or solitary
      fibrous tumor of other sites and showed reactivity for CD34 and muscle-specific
      actin, with few cells staining for desmin. The peripheral portion resembled
      leiomyoma and showed strong reactivity for actin and desmin but only focal
      staining for CD34. We interpret this tumor as mammary myofibroblastoma showing
      frank peripheral leiomyomatous differentiation. Although closely related to
      solitary fibrous tumor, mammary myofibroblastoma appears slightly different
      because of its consistent slant toward myoid differentiation in the form of actin
      and variable desmin reactivity as opposed to the rare and sparse
      immunohistochemical expression of myoid features by solitary fibrous tumors of
      other sites. This case demonstrates this phenomenon carried to an extreme, a
      feature not previously documented in mammary myofibroblastoma. It is of interest
      to note the modulation of the antigenic profile with the differentiation process,
      that is, loss of CD34 and gain of desmin accompanying the myoid differentiation.

PMID- 8980368
TI  - Cellular adhesion molecules in urologic malignancies.
AB  - Cell adhesion molecules (CAMs) are important in cell-cell interaction and
      interactions between cells and components of the extracellular matrix. CAMs have
      been associated with invasion and metastasis in a wide variety of human
      malignancies, including tumors of the genitourinary tract. Cadherins are
      transmembrane glycoproteins that bind cells by homophilic, homotypic
      interactions. Loss of expression of E-cadherin has been associated with
      dedifferentiation, invasion, and metastasis in prostate cancer and transitional
      cell neoplasia of the urinary bladder. CD44, a family of transmembrane
      glycoproteins principally involved in cell-extracellular matrix interactions,
      also has been associated with invasion and metastasis in urologic malignancies.
      Through alternative splicing, a variety of CD44 isoforms can be expressed that
      can undergo extensive posttranslational modification. CD44 variants have been
      associated with metastasis in a variety of human malignancies, particularly in
      the gastrointestinal system. Although loss of expression of CD44 standard form
      has been associated with aggressive prostate gland and bladder cancers, no
      specific isoform has been associated with metastasis of these neoplasms.
      Integrins are transmembrane glycoproteins with wide cellular distribution that
      bind a variety of extracellular matrix components. Integrins have been studied
      extensively in prostate cancer in which altered integrin expression has been
      associated with malignant prostatic epithelium. Additional adhesion molecules
      that have been studied to a variable degree in urologic malignancies include
      selectins and the immunoglobulin super-family. CAMs are fundamental to diverse
      biologic processes and appear capable of regulating intracellular signaling
      events that appear to have significant importance in human malignancy, including
      cancers of the urogenital tract.

PMID- 8980369
TI  - Smoking, alcohol consumption, and leukocyte counts.
AB  - Blood was collected from 684 healthy volunteers and examined for total and
      differential white blood cell (WBC) counts. A subgroup also was tested for
      numbers of T cells, B cells, and CD4 and CD8 subsets. Smoking status and alcohol
      consumption were determined by means of questionnaire, and smoking status was
      verified with serum cotinine concentration. High smoking rate was associated with
      increases in all counts. Former smokers abstinent less than 5 years still
      demonstrated elevated counts, whereas those abstinent more than 5 years had WBC
      counts comparable to those in persons who were never smokers. Compared with
      levels in those who had never smoked, total WBC counts were 27% higher in current
      smokers and 14% higher in former smokers who were abstinent for less than 5
      years. Lymphocyte counts were 9% higher in those consuming more than one
      alcoholic drink per day than in those consuming less alcohol, but drinking was
      not associated with other cell populations.

PMID- 8980370
TI  - Presence of t(8;21)(q22;q22) in myeloperoxidase-positive, myeloid surface antigen
      negative acute myeloid leukemia.
AB  - Although acute myeloid leukemias (AMLs) cytochemically negative for
      myeloperoxidase are now well recognized, myeloid surface antigen-negative AMLs
      are rare. The morphologic, cytochemical, immunologic, and cytogenetic or
      molecular features of such cases are described in four adults aged 19 to 60
      years. All had AML with maturation (FAB M2) and were myeloperoxidase positive.
      Immunologic studies showed all to be HLA-DR positive but negative for the CD13,
      CD14, and CD33 antigens. Two of four were CD34 antigen positive. Cytogenetic
      studies were performed in three patients, and all demonstrated t(8;21)(q22;q22).
      In studies using the reverse transcriptase polymerase chain reaction in two
      patients, including the patient in whom karytypic analysis was not performed, the
      AML1-ETO fusion product of t(8;21) was identified. These findings suggest an
      association between the lack of myeloid antigen expression in myeloperoxidase
      positive AML and the presence of t(8;21). In addition, the results demonstrate
      the continued need for cytochemical studies in the evaluation of acute leukemias.

PMID- 8980371
TI  - Recurrent Hodgkin's disease after bone marrow transplantation.
AB  - Histologic features of recurrent Hodgkin's disease (HD) after conventional
      therapy are well known, but few studies describe HD after bone marrow
      transplantation (BMT). Histologic material from 63 patients who underwent BMT
      performed to treat recurrent nodular sclerosing HD (NSHD) between 1985 and 1994
      was examined; 13 of the 63 patients had histologically proved recurrent disease
      after BMT. Histologic material and clinical findings from the original diagnostic
      biopsy specimen and pre-BMT and post-BMT specimens were available from our study
      population of eight patients (five male, three female; age range, 16 to 38 years;
      median age, 27.5 years). Seven patients had recurrent NSHD after BMT; sites of
      recurrence included lymph nodes only (four patients), and lymph nodes and lung,
      lung and liver, and lung only (one patient each). In one patient, a high-grade
      non-Hodgkin's B-cell lymphoma developed in the large intestine 5 years after BMT.
      In another, disease progressed from grade 1 in the original biopsy specimen to
      grade 2 in both the pre-BMT and post-BMT recurrent HD biopsy specimens. Post-BMT
      biopsy specimens of recurrent HD with lung involvement revealed a substantial
      increase in sclerosis and fibroblastic features. Paraffin immunoperoxidase
      studies in seven patients demonstrated substantial change in phenotype of Reed
      Stemberg cell variants in only one post-BMT recurrent HD specimen, which showed a
      +2 reaction with CD30 (Ki-1). No substantial differences in the reactive
      component were noted between the original biopsy specimen and pre-BMT and post
      BMT specimens of recurrent disease. In summary, histologic findings of post-BMT
      recurrent NSHD do not differ significantly from those of the original diagnostic
      biopsy or pre-BMT recurrent HD specimens. The lung is the most common site of
      extranodal post-BMT recurrence. In one patient, high-grade non-Hodgkin's B-cell
      lymphoma developed after BMT performed to treat recurrent HD.

PMID- 8980372
TI  - Effect of Strongyloides stercoralis infection and eosinophilia on age at onset
      and prognosis of adult T-cell leukemia.
AB  - Onset of adult T-cell leukemia (ATL) usually follows a long period of viral
      latency. Strongyloides stercoralis infection has been considered a cofactor of
      leukemogenesis. Hypereosinophilia (HE) is also observed and could be associated
      with either the presence of parasites or the leukemic process. In non-Hodgkin's
      lymphoma, eosinophilia may or may not affect prognosis. To determine whether
      infection with S stercoralis and therefore eosinophilia has a significant effect
      on the development of ATL, we studied two variables in 38 patients: age at onset
      and median survival rate. Infected (Ss+) patients (n = 19) were younger (P =
      .0002) and survived longer (P = .0006) than uninfected (Ss-) patients (n = 19)
      (median age, 39 vs 70 years; median survival, 167 vs 30 days). Mean survival of
      patients with hypereosinophilia (HE+) was not significantly different from that
      of patients without hypereosinophilia (HE-) (P = .57). However, overall survival
      was longer for Ss + HE + patients than for Ss-HE-patients (P = .01; 180 vs 30
      days) or Ss-HE + patients (P = .03; 180 vs 45 days). Among patients with mean
      survival more than 180 days, Ss + HE + patients survived longer (P = .028). Our
      data confirm that cofactors related to the environment, such as S stercoralis and
      hypereosinophilia associated with S stercoralis or human T-cell leukemia virus,
      type 1 (HTLV-1) might be important in HTLV-1-associated leukemogenesis and
      suggest that hypereosinophilia affects the prognosis of HTLV-1-associated
      leukemia.

PMID- 8980373
TI  - Hemoglobin A2 levels in healthy persons, sickle cell disease, sickle cell trait,
      and beta-thalassemia by capillary isoelectric focusing.
AB  - Simultaneously measuring major and minor hemoglobin (Hb) variants by capillary
      isoelective focusing, we obtained HbA2 intervals in healthy volunteers (n = 412)
      (reference value) and patients with HbS or beta-thalassemia. We classified normal
      HbA2 reference intervals into three age groups: 5 months or younger (1.2% +/-
      1.5%), 6 months to 1 year (2.2% +/- 0.9%), and 1 year or older (2.4% +/- 0.9%).
      These intervals were comparable to those used with other methods. Patients 1 year
      of age or older with HbS had significantly higher HbA2 levels (sickle cell trait,
      2.9% +/- 0.9%; sickle cell anemia, 2.8% +/- 1.0%; P < .05). Although reference
      HbA2 intervals overlapped those in patients with HbS, no overlap in HbA2 levels
      was noted between these groups and patients with beta-thalassemia (observed
      range, 4.3% to 7.5%). The higher than normal HbA2 interval in patients with HbS
      must be considered before a diagnosis of sickle cell trait or sickle cell disease
      with beta-thalassemia is made.

PMID- 8980374
TI  - Marginal zone B-cell lymphoma with monocytoid B-cell lymphocytes in pediatric
      patients without immunodeficiency. A report of two cases.
AB  - We report two cases of marginal zone B-cell lymphoma in two patients 6 and 18
      years of age, respectively (cases 1 and 2) who had no clinical evidence of
      immunodeficiency or risk factors for human immunodeficiency virus (HIV)
      infection. Histologic analysis in both cases revealed diffuse nodal effacement by
      a monotonous population of atypical lymphoid cells with abundant pale cytoplasm
      and round to oval nuclei, with very infrequent mitotic activity. The neoplastic
      cells in both cases were of B-cell lineage (CD20 and CD79a positive), with CD43
      coexpression. One case showed monoclonal light chain expression, and polymerase
      chain reaction analysis demonstrated clonal rearrangements of the immunoglobulin
      heavy chain gene in both cases. Abnormal cytogenetic findings were detected in
      case 2, in which metaphase spreads revealed trisomy 13 (karyotype 47, XY, +13).
      Although trisomy 13 has been described in association with acute nonlymphocytic
      leukemias and myelodysplastic syndromes, this case represents the first
      documented association of trisomy 13 with marginal zone B-cell lymphoma.
      Interphase cytogenetics analysis for trisomy 3, reported to be associated with
      mucosa-associated lymphoid tissue (MALT) lymphomas, was negative in both cases.
      Although low-grade lymphomas of the MALT type have been reported in HIV-positive
      patients, the two cases reported here are unique in that they occurred in young
      patients without HIV infection or any other evidence of immunodeficiency.

PMID- 8980375
TI  - Measurement of in vitro P-selectin expression by flow cytometry.
AB  - Measurement of in vivo platelet activation is difficult after phlebotomy and
      during blood processing for analysis. We used flow cytometry to measure platelet
      surface expression of P-selectin in the presence and absence of
      trimethylsphingosine (a platelet activation inhibitor) and compared the results
      with those from the standard methods of preventing in vitro P-selectin
      expression. Percent activation was calculated as a ratio of mean sample
      fluorescence to 100% mean fluorescence after phorbol myristate acetate treatment.
      Twenty-five micromoles per liter of trimethylsphingosine kept in vitro platelet
      activation below 5% up to 6 hours after collection and below 10% at 24 hours
      after collection. Trimethylsphingosine failed to prevent platelet activation
      caused by centrifugation, storage at 4 degrees C, or stimulation with common
      agonists. Addition of trimethylsphingosine to whole blood was valuable in
      preventing in vitro platelet activation. This compound promises to be a useful
      preservative for diagnostic testing of platelet activation.

PMID- 8980376
TI  - Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation
      testing.
AB  - The effects of 3.2% and 3.8% sodium citrate concentration on the results of
      routine coagulation assays (prothrombin time [PT] and activated partial
      thromboplastin time [aPTT]) were evaluated by means of two sets of reagents, one
      responsive and the other nonresponsive. Five groups were entered in the study:
      healthy volunteers; outpatients receiving stable oral anticoagulant therapy; and
      hospitalized patients receiving intravenous (i.v.) heparin therapy, both i.v.
      heparin and oral anticoagulant therapy, or no anticoagulant therapy. With use of
      nonresponsive PT and aPTT reagents, varying the citrate concentration has little
      clinical significance except in patients receiving i.v. heparin therapy. In
      contrast, when responsive PT and aPTT reagents are used, the concentration of
      sodium citrate anticoagulant has a significant effect on assay results. Eighteen
      percent of samples from patients receiving stable oral anticoagulant therapy
      demonstrated a change of less than 0.7 INR (International Normalized Ratio) units
      between citrate concentrations. Nineteen percent of patients receiving i.v.
      heparin therapy had a greater than 7-second difference when aPTT results were
      compared. These data demonstrate that citrate concentration affects the results
      of coagulation tests. On the basis of these data, it is recommended that 3.2%
      citrate be used for all coagulation tests.

PMID- 8980377
TI  - Assessing the efficiency of leukoreduction of cellular blood components. Use of a
      simplified formalin-fixation and batch-counting method.
AB  - To simplify the quality control procedure used to determine the efficiency and
      consistency of bedside leukoreduction, a counting protocol using prefiltration
      and postfiltration aliquots fixed in 10% formaldehyde was designed. To assess the
      reliability of the values obtained by counting the formalin-fixed samples, a
      parallel study was performed using our standard protocol of counting fresh
      propidium iodide-stained samples in a Nageotte chamber under a fluorescent
      microscope. A total of 30 single-donor platelet concentrates and 30 units of
      packed red blood cells were analyzed in parallel using the standard and formalin
      fixation methods. Furthermore, the aliquots fixed in formaldehyde were split and
      counted at 1, 3, and 30 days. The results showed no significant quantitative
      difference between the two methods. Of note is that the counts in formaldehyde
      fixed samples at 1, 3, and 30 days were consistent among themselves. The
      formaldehyde fixation of samples obtained for quality control of leukoreduction
      allows blood collection and storage at 4 degrees C and batch counting when and
      where convenient.

PMID- 8980378
TI  - Laboratory tests in evaluation of acute febrile illness in pediatric emergency
      room patients.
AB  - The rising costs of health care and the movement for health care reform have
      focused attention on methods of cost containment. Of routine laboratory and
      radiologic procedures, complete blood cell count (CBC) and determination of serum
      electrolyte values rank as high as 2nd and 9th in overall cost. We
      retrospectively studied use of the clinical laboratory to aid diagnosis of an
      acute infectious event in a pediatric emergency department population. For 5
      months, we reviewed medical records of pediatric patients younger than 15 years
      brought to the emergency department because of a febrile episode. Of 155 cases
      reviewed, electrolyte concentrations were determined in 108 patients and CBC in
      155. In all patients, either culture or rapid test for streptococcal organisms
      was performed. In addition, 838 pediatric patients with similar symptoms but who
      did not undergo laboratory testing were monitored for 100 days. Measures of
      effectiveness including sensitivity, specificity, positive and negative
      predictive values, and likelihood ratio were used to correlate specific
      laboratory findings with antibiotic therapy, serious bacterial disease, and
      culture positivity. Electrolyte abnormalities were found largely to be dismissed
      clinically, with the major clinical response consisting of parental education
      about hydration. The CBC profile was evaluated, with white blood cell count (WBC)
      indicator limits of > 10,000, > 10,000 but < 15,000, and > 15,000/mm3, and
      differentiated into absolute neutrophil count, neutrophil percent, and band cell
      percent. Temperature was evaluated as an independent variable. Insofar as serious
      bacterial disease and culture positivity, sensitivity was uniformly low (70%),
      and specificity was only marginably acceptable for WBC > 15,000 (77%). Both
      positive predictive values and likelihood ratio were low with respect to
      predicting either serious bacterial disease or culture positivity, emphasizing
      the limited usefulness of these clinical laboratory measurements. The best
      hematologic predictors of serious bacterial disease or culture positivity were
      obtained with automated hematologic analyzers and exceeded manual differential
      measurement of neutrophil percent and band cell percent. In addition, we
      correlated the administration of antibiotics with the various hematologic
      parameters and discovered that WBC > 15,000, regardless of cause, almost
      uniformly resulted in treatment (positive predictive value, 93.5%; likelihood
      ratio, 5.60). These findings support the use of automated hematology analyzer
      derived measurements and question the use of manual differential counts, unless
      specific issues are to be addressed. Furthermore, the findings seem to support
      more reliance on clinical impression and less on laboratory values.

PMID- 8980379
TI  - Medical informatics training in pathology residency programs.
AB  - Computers and information technology are increasingly used by pathologists,
      necessitating training in such technology in pathology residency programs. We
      surveyed 176 programs in the United States and Canada to assess informatics
      training in terms of instructional methods used, computer availability, and type
      of training offered. Eighty-four programs replied, for a response rate of 48%.
      Ninety percent of programs reported offering formal informatics training, but
      only 68% of programs required it. A rotation dedicated to teaching informatics
      was provided in 24% of the programs; in 44% of programs, informatics was
      integrated with other rotations. The most common instructional methods used were
      hands-on experience with microcomputers and the use of tutors. In 94% of
      programs, computers were available for resident use; in 60%, residents had
      individual computers assigned to them. Five programs offered a dedicated
      informatics rotation but did not provide residents with individual computers, and
      22 programs required informatics training but did not provide residents with
      individual computers. Comparison of these data with data from 1993 shows an
      increase in programs offering (90% vs 84%) or requiring (68% vs 59%) informatics.
      Fewer programs offer a dedicated rotation (24% vs 31%) or integrate informatics
      training with other rotations (44% vs 69%). These data suggest that although
      informatics training is considered important by most training programs,
      inadequate resources and lack of formal, structured programs may limit training.

PMID- 8980380
TI  - Computer-assisted image analysis of vascularity.

PMID- 8980381
TI  - Prothrombin time: one tube or two.

PMID- 8980382
TI  - Allelic imbalance on chromosome 5q predicts long-term survival in neuroblastoma.
AB  - Neuroblastoma is the most common extracranial solid tumour of childhood.
      Amplification of the proto-oncogene, N-myc, confers a poor prognosis in
      neuroblastoma, while hyperdiploidy is associated with a favourable outcome.
      Little is known about the contribution of tumour-suppressor genes to the
      development or progression of neuroblastoma. We examined allelic imbalance at the
      locus of the tumour-suppressor gene, APC (adenomatous polyposis coli), on
      chromosome 5q using a polymerase chain reaction (PCR)-based assay. Nine of 24
      (37.5%) informative neuroblastoma tumours showed allelic imbalance (AI) at this
      locus. Clinical data concerning N-myc amplification and DNA content were
      correlated with these results in the same patients. Allelic imbalance was found
      only in tumours containing a single copy of the N-myc gene and exhibiting
      hyperdiploidy. All nine patients with AI of chromosome 5q were alive after a
      median follow-up period of 46 months, while 7 of 15 (47%) of those lacking AI at
      this locus had died (P = 0.018). Allelic imbalance at three additional loci on
      chromosome 5 was demonstrated in tumours that exhibited AI at the APC locus,
      suggesting that endoreduplication of chromosome 5 had occurred. Fluorescent in
      situ hybridisation (FISH) analysis of tumour tissue from one patient exhibiting
      AI demonstrated two, three, four or six copies of the APC gene per cell,
      consistent with this hypothesis. These data suggest that allelic imbalance of
      chromosome 5 is involved in at least a subset of neuroblastomas and influences
      survival in patients with neuroblastoma.

PMID- 8980383
TI  - Overexpression and activation of hepatocyte growth factor/scatter factor in human
      non-small-cell lung carcinomas.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasive growth
      of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both
      the receptor and the ligand are detected, and the latter is known to be a
      mitogenic and a motogenic factor for both cultured bronchial epithelial cells and
      non-small-cell carcinoma lines. Here, ligand and receptor expression was examined
      in 42 samples of primary human non-small-cell lung carcinoma of different
      histotype. Each carcinoma sample was compared with adjacent normal lung tissue.
      The Met/HGF receptor was found to be 2 to 10-fold increased in 25% of carcinoma
      samples (P = 0.0113). The ligand, HGF/SF, was found to be 10 to 100-fold
      overexpressed in carcinoma samples (P < 0.0001). Notably, while HGF/SF was
      occasionally detectable and found exclusively as a single-chain inactive
      precursor in normal tissues, it was constantly in the biologically-active
      heterodimeric form in carcinomas. Immunohistochemical staining showed homogeneous
      expression of both the receptor and the ligand in carcinoma samples, whereas
      staining was barely detectable in their normal counterparts. These data show that
      HGF/SF is overexpressed and consistently activated in non-small-cell lung
      carcinomas and may contribute to the invasive growth of lung cancer.

PMID- 8980384
TI  - Differential expression of DNA topoisomerase II alpha and -beta in P-gp and MRP
      negative VM26, mAMSA and mitoxantrone-resistant sublines of the human SCLC cell
      line GLC4.
AB  - Sublines of the human small-cell lung carcinoma (SCLC) cell line GLC4 with
      acquired resistance to teniposide, amsacrine and mitoxantrone (GLC4/VM20x,
      GLC4/AM3x and GLC4/MIT60x, respectively) were derived to study the contribution
      of DNA topoisomerase II alpha and -beta (TopoII alpha and -beta) to resistance
      for TopoII-targeting drugs. The cell lines did not overexpress P-glycoprotein or
      the multidrug resistance-associated protein but were cross-resistant to other
      TopoII drugs. GLC4/VM20x showed a major decrease in TopoII alpha protein (54%;
      for all assays presented in this paper the GLC4 level was defined to be 100%)
      without reduction in TopoII beta protein; GLC4/AM3x showed only a major decrease
      in TopoII beta protein (to 18%) and not in TopoII alpha. In GLC4/MIT60x, the
      TopoII alpha and -beta protein levels were both decreased (TopoII alpha to 31%;
      TopoII beta protein was undetectable). The decrease in TopoII alpha protein in
      GLC4/VM20x and GLC4/MIT60x, was mediated by decreased TopoII alpha mRNA levels.
      Loss of TopoII alpha gene copies contributed to the mRNA decrease in these cell
      lines. Only in the GLC4/MIT60x cell line was an accumulation defect observed for
      the drug against which the cell line was made resistant. In conclusion, TopoII
      alpha and -beta levels were decreased differentially in the resistant cell lines,
      suggesting that resistance to these drugs may be mediated by a decrease in a
      specific isozyme.

PMID- 8980385
TI  - The level of MnSOD is directly correlated with grade of brain tumours of
      neuroepithelial origin.
AB  - The oxy-radical scavenger enzyme manganese superoxide dismutase (MnSOD) may act
      in the capacity of a tumour-suppressor gene. To address the issue of its role in
      tumour transformation and progression in vivo, we evaluated the content of this
      enzyme in 33 brain tumours of neuroepithelial origin with different degrees of
      differentiation (WHO grade II-IV) by means of Western blot and immunohistology.
      Our results show that immunoreactive MnSOD increases in a direct relationship
      with tumour grade and is therefore inversely correlated with differentiation. The
      increase in induced at a pretranscriptional level and is apparently specific to
      brain tumours of neuroepithelial origin. Approximately 30% of grade IV tumours
      display low levels of MnSOD content, and preoperative radiotherapy and
      brachytherapy result in low amounts of enzyme. Based upon these observations, we
      suggest that MnSOD cannot be considered a classical tumour-suppressor gene.

PMID- 8980386
TI  - Serum albumin as a vehicle for zinc phthalocyanine: photodynamic activities in
      solid tumour models.
AB  - Zinc phthalocyanine (ZnPc) is a second-generation photosensitiser for the
      photodynamic therapy (PDT) of cancer. Unsubstituted ZnPc is, however, highly
      insoluble in most common solvents, and for clinical applications the material
      needs to be incorporated in liposomes. We report a simple, alternative procedure
      to formulate ZnPc through non-covalent binding to bovine serum albumin (BSA).
      Intravenous administration of ZnPc-BSA preparations, at a molar ratio of 11:1 and
      at a ZnPc dose equivalent to 0.5 mol kg-1, to tumour-bearing mice followed 24 h
      later by PDT was shown to provide tumour control in two different models, the EMT
      6 tumour in Balb/c mice and the human colon T380 carcinoma in nude mice. Analysis
      of serum fractions from treated animals showed that ZnPc readily redistributes
      over the serum high-density lipoprotein (HDL) fraction. We also demonstrated the
      absence of hepatic toxicity of the ZnPc-BSA preparation by monitoring the hepatic
      cytochrome P450 activity in treated animals and the viability of human cultured
      hepatocytes.

PMID- 8980387
TI  - Tumour-localising and -photosensitising properties of a novel zinc(II)
      octadecylphthalocyanine.
AB  - 1,4,8,11,15,18,22,25-Octadecylphthalocyaninato zinc(II), ZnODPc, incorporated
      into a Cremophor emulsion, was assayed for its pharmacokinetic and
      phototherapeutic properties in Balb/c mice bearing an intramuscularly
      transplanted MS-2 fibrosarcoma. The phthalocyanine was injected intravenously
      (i.v.) in three doses, i.e. 1.46, 0.73 and 0.37 mumol kg-1 body weight. In all
      cases, the octadecyl-substituted phthalocyanine showed an unusually high affinity
      for serum low-density lipoproteins (LDLs) and a high efficiency and selectivity
      of tumour targeting: the maximum accumulation in the tumour occurred at 24 h
      after injection, whereas no detectable amount of phthalocyanine was recovered
      from the muscle, i.e. the peritumoral tissue, between 1 h and 1 week after
      injection. At the same time, low amounts of phthalocyanine were recovered from
      skin and then only at short times after injection, with skin photosensitivity
      rapidly disappearing and the phthalocyanine present in the serum only. Tumour
      photosensitisation studies were carried out at 24 h after administration of 1.46
      mumol kg-1 ZnODPc and showed that this phthalocyanine has a very high
      phototherapeutic efficiency; this is probably a consequence of the multiple
      mechanisms by which the phthalocyanine induces tumour damage, involving both
      direct modification of malignant cells and impairment of blood flow, as well as
      the alteration of a variety of subcellular components, such as mitochondria, the
      rough endoplasmic reticulum, the perinuclear membrane and, occasionally, cell
      nuclei. Tumour necrosis appears to be the consequence of both random cell death
      and apoptosis.

PMID- 8980388
TI  - Increased susceptibility to metastasis during pro-oestrus/oestrus in rats:
      possible role of oestradiol and natural killer cells.
AB  - It has been suggested that tumour development and immunocompetence are affected
      by the menstrual and the oestrous cycle, and sex hormones have been shown to
      modulate lymphokine production, neuroendocrine activity and immunity. In this
      study, we assessed natural killer cell activity and host susceptibility to
      metastasis during the oestrous cycle in the Fischer 344 inbred rat strain.
      Females were inoculated intravenously with MADB106 tumour cells, a syngeneic
      mammary adenocarcinoma cell line that metastasises only to the lungs. The
      susceptibility to metastatic development of this tumour was found to be
      significantly higher during pro-oestrus and oestrus than during metoestrus and
      dioestrus. Two days of exposure to oestradiol benzoate caused similar effects in
      ovariectomised females, and a single administration of progesterone reduced this
      effect of oestradiol to a statistically non-significant level. The tumour was
      found to be negative for oestradiol receptors, and its in vitro proliferation
      rate was not affected by oestradiol or progesterone, suggesting that the effects
      of sex hormones on the metastatic process are not attributable to a direct effect
      on tumour cells. Because the metastatic process of MADB106 tumour cells is known,
      and confirmed here, to be highly controlled by large granular lymphocyte/natural
      killer (LGL/NK) cell activity, we assessed their role in mediating the effects of
      the oestrous cycle. The number and activity levels of circulating blood LG/NK
      cells (NKR-PI+ bright) were studied. Findings indicated oestrous-dependent
      alterations in the number of LGL/NK cells and suggested a diminished NK activity
      per LGL/NK cell during pro-oestrus/ oestrus, the same phases that were
      characterised by higher susceptibility to metastatic development. These findings
      provide the first empirical evidence for a causal relationship between a short
      term exposure to elevated oestradiol/low progesterone levels and decreased
      resistance to tumour metastasis, and it is hypothesised that an alteration in
      LGL/NK cell activity underlies these effects. Homologies and relevance to
      clinical phenomena are discussed.

PMID- 8980389
TI  - Synergistic effects of TNF-alpha and melphalan in an isolated limb perfusion
      model of rat sarcoma: a histopathological, immunohistochemical and electron
      microscopical study.
AB  - Isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF-alpha) and
      melphalan has shown impressive results in patients with irresectable soft tissue
      sarcomas and stage III melanoma of the extremities. The mechanisms of the
      reported in vivo synergistic anti-tumour effects of TNF-alpha and melphalan are
      not precisely understood. We have developed an ILP model in the rat using a non
      immunogenic sarcoma in which similar in vivo synergy is observed. The aim of this
      present study was to analyse the morphological substrate for this synergistic
      response of TNF-alpha in combination with melphalan to shed more light on the
      pathomechanisms involved. Histology of the tumours from saline- (n = 14) and
      melphalan-treated (n = 11) rats revealed apparently vital tumour cells in over
      80% of the cross-sections. Interstitial oedema and coagulation necrosis were
      observed in the remaining part of the tumour. Haemorrhage was virtually absent.
      TNF-alpha (n = 22) induced marked oedema, hyperaemia, vascular congestion,
      extravasation of erythrocytes and haemorrhagic necrosis (20-60% of the cross
      sections). Oedema and haemorrhage suggested drastic alterations of permeability
      and integrity of the microvasculature. Using light and electron-microscopy, we
      observed that haemorrhage preceded generalised platelet aggregation. Therefore,
      we suggest that the observed platelet aggregation was the result of the
      microvascular damage rather than its initiator. Remarkably, these events hardly
      influenced tumour growth. However, perfusion with the combination of TNF-alpha
      and melphalan (n = 24) showed more extensive haemorrhagic necrosis (80-90% of the
      cross-sections) and revealed a prolonged remission (mean 11 days) in comparison
      with the other groups of rats. Electron microscopical analysis revealed similar
      findings as described after TNF-alpha alone, although the effects were more
      prominent at all time points after perfusion. In conclusion, our findings suggest
      that the enhanced anti-tumour effect after the combination of TNF-alpha with
      melphalan results from potentiation of the TNF-alpha-induced vascular changes
      accompanied by increased vascular permeability and platelet aggregation. This may
      result in additive cytotoxicity or inhibition of growth of residual tumour cells.

PMID- 8980390
TI  - In vivo experimental evidence that the nitric oxide pathway is involved in the X
      ray-induced antiangiogenicity.
AB  - We have investigated both the effects of X-rays on angiogenesis and the possible
      role of nitric oxide (NO) on the observed antiangiogenic effect of X-rays, using
      as an in vivo model the chick embryo chorioallantoic membrane (CAM). These
      effects were assessed both morphologically and biochemically, by measuring
      vascular density and collagenous protein biosynthesis, respectively, on days 9
      and 14 of the chick embryo development. Vascular density and cytotoxicity of the
      CAM were also evaluated histologically. We have shown that X-rays have an
      antiangiogenic effect on the system used and that the NO synthase inhibitor NG
      nitro-L-arginine methyl ester (L-NAME) promoted angiogenesis of the non
      irradiated CAM and reversed the antiangiogenic effect of irradiation. D-NAME,
      which is an inactive enantiomer of L-NAME, showed no such effects. L-Arginine,
      which is the substrate for NO synthase, had a modest antiangiogenic effect on the
      non-irradiated CAM, no effect on the irradiated CAM and abolished the angiogenic
      effect of L-NAME on these CAM preparations. These results suggest that NO is
      involved in the antiangiogenic mechanism of X-rays and that pharmacological
      manipulation of NO firstly, may offer a better understanding of these mechanisms
      and, secondly, may also prove to be an alternative therapeutic approach for
      treating pathological conditions involving angiogenesis.

PMID- 8980391
TI  - Effect of melphalan and hyperthermia on p34cdc2 kinase activity in human melanoma
      cells.
AB  - We previously reported that combined treatment with melphalan and mild
      hyperthermia (1 h at 42 degrees C) caused a synergistic cytotoxic effect in JR8
      melanoma cells, paralleled by a stabilisation of a melphalan-induced G2-phase
      cell block. In this study, we investigated the effect of melphalan and
      hyperthermia on proteins that regulate G2-M transition. Neither hyperthermia nor
      melphalan at a concentration of 2.5 micrograms ml-1, which had no
      antiproliferative effect at 37 degrees C, interfered with cyclin B1 expression or
      p34cdc2 kinase activity. At a concentration of 8.5 micrograms ml-1, which reduced
      cell growth by 50% at 37 degrees C, melphalan inhibited p34cdc2 kinase activity
      as a consequence of an increased tyrosine phosphorylation of the protein. A
      similar inhibitory effect on p34cdc2 kinase was obtained when the lowest
      melphalan concentration (2.5 micrograms ml-1) was used under hyperthermic
      conditions. Our results indicate that thermal enhancement of melphalan
      cytotoxicity could be mediated at least in part by an inhibition of p34cdc2
      kinase activity, which prevents cell progression into mitosis.

PMID- 8980392
TI  - P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells
      in vivo.
AB  - We examined whether the increased expression of P-glycoprotein (P-gp) encoded by
      the human multidrug resistance gene MDR1 is related to the acquired multidrug
      resistance of lung cancer in vivo. We estimated the chemosensitivity of lung
      cancer xenografts (LC-6, adenocarcinoma; Lu-24, small-cell cancer) by calculation
      of relative tumour growth (T/C%, treated/control) in vivo, based on statistical
      significance determined by the Mann-Whitney U test (P < 0.01, one-sided). MDR1
      gene expression levels were evaluated by reverse transcription-polymerase chain
      reaction (RT-PCR) assay. P-gp production and P-gp localisation were examined by
      Western blotting and by immunohistochemical analysis respectively. LC-6 and Lu-24
      were initially sensitive to both vincristine (VCR, 1.6 mg kg-1: LC-6, 45%; Lu-24,
      39%) and doxorubicin (DOX, 12 mg kg-1: LC-6, 26%; Lu-24, 27%) in vivo. VCR
      resistant variants (LC-6R, 66% and Lu-24R, 68%) selected with VCR (0.4 mg kg-1, x
      9) significantly acquired cross-resistance to DOX (LC-6R, 55% and Lu-24R, 55%
      respectively). RT-PCR assay showed increased levels of MDR1 expression in LC-6R
      and Lu-24R with stable MDR1 expression levels. P-gp expression levels were
      elevated, and the percentage of P-gp-positive tumour cells increased in both LC
      6R and Lu-24R. These results suggest that P-gp/MDR1 overexpression is related to
      acquired multidrug resistance in lung cancer in vivo.

PMID- 8980393
TI  - The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow
      cytometric study.
AB  - We have used flow cytometry to study the mechanism of cytotoxic action of a
      series of ammine/amine Pt(IV) dicarboxylates [ammine
      diacetatodichloro(cyclohexylamine) platinum(IV), JM216; ammine
      dibutyratodichloro(cyclohexylamine)platinum(IV), JM221; ammine
      diacetatodichloro(propylamine)platinum(IV), JM223; ammine
      dibenzoatodichloro(propylamine)platinum(IV), JM244]. JM216 has been shown to have
      clinical potential and has recently entered phase II trials. All the compounds
      caused a slowdown in S-phase transit followed by a block in G2. Cells died either
      through apoptosis (largely during S-phase) or by failing to overcome the G2 block
      (some days after treatment). In G2, the cells either divided or enlarged and
      died. At equitoxic doses, JM216 showed the most apoptotic cells and had the most
      platinum bound to the DNA; JM244 showed the fewest apoptotic cells and had the
      least platinum bound to DNA. We suggest that whether apoptosis was triggered or
      not was governed by the total amount of Pt bound to the DNA; the type of lesion
      was more important in determining whether a cell became blocked in G2.

PMID- 8980394
TI  - Multicentre phase II pharmacological evaluation of rhizoxin. Eortc early clinical
      studies (ECSG)/pharmacology and molecular mechanisms (PAMM) groups.
AB  - Rhizoxin is a macrocyclic lactone compound that binds to tubulin and inhibits
      microtubule assembly. Rhizoxin demonstrated preclinical anti-tumour activity
      against a variety of human tumour cell lines and xenograft models. Phase I
      evaluation found a maximum tolerated rhizoxin dose of 2.6 mg m-2, with
      reversible, but dose-limiting, mucositis, leucopenia and diarrhoea. Clinical
      trials were then initiated by the EORTC ECSG in melanoma, breast, head and neck,
      and non-small-cell lung cancers with the recommended phase II rhizoxin dose of 2
      mg m-2. Pharmacological studies were instituted with the phase II trials to
      complement the limited pharmacokinetic data available from the phase I trial.
      Blood samples were obtained from 69 of 103 eligible patients enrolled in phase II
      rhizoxin studies, and these were evaluable for pharmacokinetic analysis in 36
      patients. Plasma rhizoxin concentrations were determined by high-performance
      liquid chromatography (HPLC), and post-distribution pharmacokinetic parameters
      were estimated by a one-compartment model. Rhizoxin was rapidly eliminated from
      plasma, with a median systemic clearance of 8.41 min-1 m-2 and an elimination
      half-life of 10.4 min. Rhizoxin area under the concentration-time curve (AUC) was
      higher in patients obtaining a partial response or stable disease than in those
      with progressive disease (median 314 vs 222 ng ml-1 min; P = 0.03). As predicted
      from previous studies, haematological and gastrointestinal toxicity was observed,
      but could not be shown to be related to rhizoxin AUC. This study demonstrated the
      rapid and variable elimination of rhizoxin from the systemic circulation. The
      presence of pharmacodynamic relationships and the low level of systemic toxicity
      suggest that future trials of rhizoxin with alternative dosage or treatment
      schedules are warranted.

PMID- 8980395
TI  - Acceleration of MRP-associated efflux of rhodamine 123 by genistein and related
      compounds.
AB  - Multidrug resistance (MDR), caused by overexpression of either P-glycoprotein or
      the multidrug resistance protein (MRP), is characterised by a decreased cellular
      drug accumulation due to an enhanced drug efflux. In this study, we examined the
      effects of genistein and structurally related (iso)flavonoids on the transport of
      rhodamine 123 (Rh123) and daunorubicin in the MRP-overexpressing MDR lung cancer
      cell lines COR-L23/R and MOR/R. Genistein, genistin, daidzein and quercetin
      showed major differences in effects on Rh123 vs daunorubicin transport in the MRP
      mediated MDR cell lines: the accumulation of daunorubicin was increased, whereas
      the accumulation of Rh123 was decreased by the flavonoids. The depolarisation of
      the membrane potential caused by genistein might be involved in the acceleration
      of the efflux of Rh123 measured in the MRP-overexpressing cell lines. These
      observations should be taken into account when using fluorescent dyes as probes
      for determination of transporter activity as a measure of MDR.

PMID- 8980396
TI  - Reduced capacity of tumour blood vessels to produce endothelium-derived relaxing
      factor: significance for blood flow modification.
AB  - The effect of nitric oxide-dependent vasodilators on vascular resistance of
      tumours and normal tissue was determined with the aim of modifying tumour blood
      flow for therapeutic benefit. Isolated preparations of the rat P22 tumour and
      normal rat hindlimb were perfused ex vivo. The effects on tissue vascular
      resistance of administration of sodium nitroprusside (SNP) and the
      diazeniumdiolate (or NONO-ate) NOC-7, vasodilators which act via direct release
      of nitric oxide (NO), were compared with the effects of acetylcholine (ACh), a
      vasodilator which acts primarily via receptor stimulation of endothelial cells to
      release NO in the form of endothelium-derived relaxing factor (EDRF). SNP and NOC
      7 effectively dilated tumour blood vessels after preconstriction with
      phenylephrine (PE) or potassium chloride (KCl) as indicated by a decrease in
      vascular resistance. SNP also effectively dilated normal rat hindlimb vessels
      after PE/KCl constriction. Vasodilatation in the tumour preparations was
      accompanied by a significant rise in nitrite levels measured in the tumour
      effluent. ACh induced a significant vasodilation in the normal hindlimb but an
      anomalous vasoconstriction in the tumour. This result suggests that tumours,
      unlike normal tissues are incapable of releasing NO (EDRF) in response to ACh.
      Capacity for EDRF production may represent a difference between tumour and normal
      tissue blood vessels, which could be exploited for selective pharmacological
      manipulation of tumour blood flow.

PMID- 8980397
TI  - Overexpression of the ABC transporter TAP in multidrug-resistant human cancer
      cell lines.
AB  - Multidrug resistance (MDR) to anti-cancer drugs has been associated with the
      overexpression of P-glycoprotein (P-gp) and the multidrug resistance-associated
      protein (MRP), both being members of the ATP-binding cassette (ABC) superfamily
      of transporters. We investigated whether in addition to P-gp and MRP, another ABC
      transporter, the transporter associated with antigen processing (TAP), is
      associated with MDR. TAP plays a major role in MHC class I-restricted antigen
      presentation by mediating peptide translocation over the endoplasmic reticulum
      membrane. TAP1 and P-gp share a significant degree of homology among their
      transmembrane domains, which are thought to be the primary determinants of
      substrate specificity, and both can apparently mediate the translocation of
      peptides. Using immunocytochemistry and Western blot, TAP was overexpressed in
      parallel with MHC class I in several MDR human cancer cell lines. TAP was
      overexpressed more frequently in MRP-positive MDR cell lines (three out of three)
      than in P-gp positive MDR cells (two out of five). Reversal of resistance
      resulted in a decrease in TAP levels. Transfection of the TAP genes into TAP
      deficient lymphoblastoid T2 cells conferred mild resistance to etoposide,
      vincristine and doxorubicin (2- to 2.5-fold). Furthermore, etoposide and
      vincristine inhibited TAP-dependent peptide translocation to the endoplasmic
      reticulum. Collectively, our results suggest that TAP may modestly contribute to
      the MDR phenotype, in particular in MRP- overexpressing MDR cells. Further
      insight into the role of TAP in MDR will require the study of other
      transfectants, as well as the investigation of TAP expression in P-gp and MRP
      negative MDR cancer cell lines.

PMID- 8980398
TI  - Fractional allele loss data indicate distinct genetic populations in the
      development of non-small-cell lung cancer.
AB  - Allelic imbalance or loss of heterozygosity (LOH) has been widely used to assess
      genetic instability in tumours, and high LOH on chromosome arms 3p, 9p and 17p
      has been considered to be a common event in non-small-cell lung cancer (NSCLC).
      We have investigated allelic imbalance in 45 NSCLCs using 92 microsatellite
      markers on 38 chromosome arms. LOH of 38% was observed on 3p using nine markers,
      58% on 9p using 15 markers and 38% on 17p using five markers. Fractional allele
      loss (FAL) has been calculated for each tumour (FAL is the number of chromosome
      arms showing LOH/number of informative chromosome arms) and a median FAL value of
      0.09 was obtained in the 45 NSCLCs studied. The LOH data were examined on the
      basis of FAL scores: low FAL (LFAL) (0.00-0.04), medium FAL (MFAL) (0.05-0.13)
      and high FAL (HFAL) (0.14-0.45) based symmetrically around the median FAL value
      of 0.09. Tumours with HFAL values showed a very clear polarisation of the LOH
      data on chromosome arms 3p, 9p and 17p, such that 80% showed loss on 3p, 80% on
      9p and 73% on 17p. These incidences of LOH were significantly higher than would
      be expected, since overall genetic instability in these HFAL tumours ranged from
      14% to 45% LOH. Nine of the 14 patients in the LFAL group were found to have no
      LOH on 3p, 9p or 17p, but five of these had LOH at other sites: i.e. LOH on 5p,
      5q, 8p, 13q, 16q and 19q. These results indicate that LFAL patients form a new
      subset of NSCLC tumours with distinct molecular-initating events, and may
      represent a discrete genetic population.

PMID- 8980399
TI  - MYCL genotypes and loss of heterozygosity in non-small-cell lung cancer.
AB  - Some studies have suggested that the S allele of the MYCL oncogene, which results
      from an intragenic EcoRI restriction fragment length polymorphism (RFLP), may be
      associated with cancer susceptibility. In addition, this allele has also been
      linked to metastases and adverse survival in certain cancers, although studies of
      lung cancer patients from different populations have yielded controversial
      results. We studied 108 cases of surgical resected non-small-cell lung cancer
      (NSCLC) and found no evidence that MYCL genotypes were associated with tumour
      progression or a worse prognosis. However, the presence of loss of heterozygosity
      (LOH) at this chromosome 1p32 locus correlated significantly with regional lymph
      node involvement, as well as advanced TNM stage. These data indicate the
      existence of a chromosome 1p candidate tumour-suppressor gene(s), possibly in
      linkage disequilibrium with the EcoRI RFLP in specific populations, which appears
      to play a role in determining tumour progression in NSCLC. Refined mapping of the
      critical region of loss should help attempts to identify and clone the candidate
      gene.

PMID- 8980400
TI  - Deletion mapping on chromosome 10q25-q26 in human endometrial cancer.
AB  - To understand genetic events which play a role in the development and/or
      progression of human endometrial cancer, we studied allelotypes on all autosomal
      chromosomes, as well as chromosome X, with 42 microsatellite markers and 56
      endometrial cancers. The most frequent loss of heterozygosity (LOH) was observed
      on the long arm of chromosome 10 (14 of 30, 47%), which was commonly detected in
      grade 1 cancer. We constructed a detailed deletion map and defined two commonly
      deleted regions in 10q25-q26; one was the 8 cM region between D10S209 and
      D10S216, the other was the 12 cM region between D10S217 and D10S590. Replication
      errors at two or more loci were observed in 24 of 56 tumours (43%), suggesting
      that disruption of the DNA mismatch repair system also plays an important role in
      the course of endometrial carcinogenesis.

PMID- 8980401
TI  - DNA amplifications at 20q13 and MDM2 define distinct subsets of evolved breast
      and ovarian tumours.
AB  - DNA amplification seems to be particularly frequent in human breast tumours and
      has been associated with cancer evolution and aggressiveness. Recent data
      indicate that new events should be added to the list, such as the amplifications
      at chromosome 20q13 or the MDM2 gene. The present work aimed at determining the
      incidence and clinicopathological signification of these amplifications in a
      large series of breast and ovarian tumours. We tested 1371 breast and 179 ovarian
      tumours by Southern blotting and observed amplification of 20q13 in 5.4% breast
      and 2.8% ovarian carcinomas, whereas MDM2 was found amplified in 5.3% and 3.8% of
      breast and ovarian tumours respectively. MDM2 RNA expression levels were analysed
      in a subset of 57 breast tumours and overexpression was observed in 4/57 (7%) of
      the tumours. Elevated expression levels coincided with amplification of the gene.
      In breast cancer, 20q13 and MDM2 amplifications seem to define subsets of
      aggressive tumours. Indeed, 20q13 was correlated to axillary nodal involvement
      and occurred preferentially in younger patients (< 50 years). Furthermore, 20q13
      correlated, as did MDM2 amplification, to aneuploidy. In parallel, we had also
      tested our tumour DNAs for amplification of CCND1, ERBB-2 and MYC, which made it
      possible to test for correlations with 20q13 or MDM2 amplifications. Whereas
      20q13 showed a very strong correlation to CCND1 amplification, that of MDM2 was
      prevalent in MYC-amplified tumours. Interestingly, 20q13 and MDM2 amplifications
      showed some degree of correlation to each other, which may possibly be owing to
      the fact that both events occurred preferentially in aneuploid tumours. In
      ovarian cancer, no statistically significant correlation was observed. However,
      20q13 amplification occurred preferentially in stage 3 tumours and MDM2 was
      correlated to ERBB-2 amplification. This may suggest that in ovarian tumours
      also, 20q13 and MDM2 amplifications occur in late or aggressive cancers.

PMID- 8980403
TI  - CAM 17.1--a new diagnostic marker in pancreatic cancer.
AB  - CAM 17.1-Ab is a recently described monoclonal antibody that detects a mucus
      glycoprotein with high specificity for intestinal mucus, particularly in the
      colon, small intestine, biliary tract and pancreas. We investigated the
      expression and release of CAM 17.1 in pancreatic carcinoma cell lines and tissue
      specimens of normal pancreas, chronic pancreatitis and pancreatic cancer. CAM
      17.1 was weakly expressed on normal ductal cells and chronic pancreatitis,
      whereas it was overexpressed in pancreatic cancer. Serum analysis using a new
      enzyme-linked antibody sandwich assay (CAM 17.1/WGA) of patients with chronic
      pancreatitis, pancreatic cancer or other gastrointestinal cancer and of healthy
      blood donors revealed a high sensitivity (67%) and excellent specificity (90%) of
      CAM 17.1/WGA assay in pancreatic cancer. In comparison with the tumour marker
      CA19-9, the sensitivity of the CAM 17.1/WGA assay was similar to the sensitivity
      of CA 19-9 (67% and 76%, P = 0.22), whereas the specificity of CAM 17.1/WGA assay
      was higher than in CA 19-9 (90% compared with 78% in chronic pancreatitis, P >
      0.05).

PMID- 8980402
TI  - The expression and localisation of beta-nerve growth factor (beta-NGF) in benign
      and malignant human prostate tissue: relationship to neuroendocrine
      differentiation.
AB  - beta-NGF is a determinant of sympathetic innervation and a neural differentiation
      factor. In the present study, we have examined 15 benign prostatic hyperplastic
      and 15 prostate cancer patients for the expression and localisation of beta-NGF
      by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting,
      immunohistochemistry and ELISA. We have correlated the beta-NGF concentrations to
      prostate morphometry and neuroendocrine differentiation. The presence of beta NGF
      mRNA transcripts was confirmed by RT-PCR where a 542 bp product was found with
      specific primers for the human beta-NGF cDNA sequence. The presence of the
      peptide was also confirmed by Western blot analysis which showed a protein co
      migrating with recombinant human beta-NGF. Our results demonstrate that beta-NGF
      is localised to prostate epithelium, and the concentrations of the peptide were
      not significantly different in malignant (mean +/- s.d.; 3100 +/- 1502 pg g-1 wet
      weight of tissue) than in benign tissues (1992 +/- 684 pg g-1, P = 0.512). We
      were, however, unable to correlate the concentrations of beta-NGF to
      neuroendocrine differentiation in malignant tissues. Clearly, the present study
      demonstrates that beta-NGF is a product of the prostate and may be involved in
      the control of the sympathetic innervation of the human prostate.

PMID- 8980404
TI  - Expression of autocrine motility factor receptor correlates with disease
      progression in human gastric cancer.
AB  - Up-regulation of autocrine motility factor receptor (AMF-R) expression has been
      shown to be associated with invasion and metastasis of experimental tumour
      systems and human neoplasms. Monoclonal antibodies against AMF-R (gp78) were used
      to stain 221 primary gastric cancer specimens, and level of expression was
      examined in relation to pathological stage and prognostic values. In 125 out of
      221 (56.6%) patients, gp78 was detected. Expression of gp78 was associated with
      macroscopic type, lymphatic and venous invasions, and lymph node and peritoneal
      metastasis. The level of gp78 expression in the cancer specimens was associated
      with histopathological stage and grade of tumour penetration. Positive gp78
      expression was significantly associated with poor prognosis (P < 0.001). This
      significant relationship remained among patients in stage II and III. The results
      suggest that gp78 expression could be used as a prognostic marker in gastric
      cancer patients.

PMID- 8980405
TI  - Weekly doxorubicin and continuous infusional 5-fluorouracil for advanced breast
      cancer.
AB  - Drug scheduling alterations can improve the therapeutic index of both 5
      fluorouracil and anthracyclines. We investigated a regimen of weekly doxorubicin
      and continuous infusional 5-fluorouracil (AcF) in loco-regionally recurrent and
      metastatic breast cancer. The aims of this phase II study were to use low-dose
      weekly anthracyclines in a patient group where liver metastases are a frequent
      problem, to optimise scheduling of 5-fluorouracil using continuous infusion and
      to conserve alkylating agent use for late intensification in responding patients.
      Fifty-six patients received 5-fluorouracil 200 mg m-2 day-1 and doxorubicin 20-30
      mg m-2 week-1 for at least 6 weeks. Sixty-two percent were chemonaive. Patients
      were evaluated for dose intensity, response, toxicity and survival. Of the
      assessable patients, 76% achieved UICC response criteria (20% complete response,
      56% partial response). WHO grade 3+ toxicities were: alopecia, 98%; mucositis,
      62%; neutropenia, 22%; and grade 3 palmar-plantar syndrome, 24%. Median survival
      was 13 months, with visceral metastasis conferring a significantly worse outcome
      (P = 0.03). Grade 3+ mucositis was more frequent with planned doxorubicin dose
      intensity > or = 25 mg m-2 week-1 (P = 0.04). AcF is highly active in breast
      cancer with acceptable toxicities and can be used before alkylating agent-based
      high-dose therapy.

PMID- 8980406
TI  - High-dose chemotherapy supported by peripheral blood progenitor cells in poor
      prognosis metastatic breast cancer--phase I/II study. Edinburgh Breast Group.
AB  - Current treatments for metastatic breast cancer are not associated with
      significant survival benefits despite response rates of over 50%. High-dose
      therapy with autologous bone marrow transplantation (ABMT) has been investigated,
      particularly in North America, and prolonged survival in up to 25% of women has
      been reported, but with a significant treatment-related mortality. However, in
      patients with haematological malignancies undergoing autologous transplantation,
      haematopoietic reconstruction is significantly quicker and mortality lower than
      with ABMT, when peripheral blood progenitor cells (PBPCs) are used. In 32 women
      with metastatic breast cancer, we investigated the feasibility of PBPC
      mobilisation with high-dose cyclophosphamide and granulocyte colony-stimulating
      factor (G-CSF) after 12 weeks' infusional induction chemotherapy and the
      subsequent efficacy of the haematopoietic reconstitution after conditioning with
      melphalan and either etoposide or thiotepa. PBPC mobilisation was successful in
      28/32 (88%) patients, and there was a rapid post-transplantation haematopoietic
      recovery: median time to neutrophils > 0.5 x 10(9) l-1 was 14 days and to
      platelets > 20 x 10(9) l-1 was 10 days. There was no procedure-related mortality,
      and the major morbidity was mucositis (WHO grade 3-4) in 18/32 patients (56%). In
      a patient group of which the majority had very poor prognostic features, the
      median survival from start of induction chemotherapy was 15 months. Thus, PBPC
      mobilisation and support of high-dose chemotherapy is feasible after infusional
      induction chemotherapy for patients with metastatic breast cancer, although the
      optimum drug combination has not yet been determined.

PMID- 8980407
TI  - Interleukin 2 and interferon alpha-2a do not improve anti-tumour activity of 5
      fluorouracil in advanced colorectal cancer.
AB  - Treatment using a combination of 5-fluorouracil (5-FU), interferon-alpha (IFN
      alpha-2a) and interleukin 2 (IL-2) has been shown to mediate disease regression
      in selected patients with advanced colorectal cancer. This phase II study was
      designed to evaluate the anti-tumour activity and toxicity of the combination of
      IL-2, IFN alpha-2a and 5-FU in patients with advanced colorectal cancer. Forty
      four patients with metastatic colorectal cancer were treated, predominantly on an
      outpatient basis, with subcutaneous IFN alpha-2a and IL-2 three times per week
      followed by once a week bolus intravenous 5-FU injections. There were six (14%)
      partial responses among the 43 evaluable patients [95% confidence interval (CI) 5
      28%]. Twenty-four patients had stable disease (56%) and 13 patients (30%) showed
      progressive disease. The median time to progressive disease in 43 patients was 19
      weeks (range 2-72 weeks) and in responders 34 weeks (range 24-30 weeks). The
      median overall survival was 47 weeks (range 2-85 weeks) and in responders 60
      weeks (range 35-71 weeks). Treatment-related toxic effects included fatigue,
      nausea and vomiting. Granulocytopenia was the main reason for the dose reductions
      or treatment interruptions in 32 out of 44 patients. One patient died of toxicity
      due to renal failure. Serial assessments of immunophenotyping and cytolytic
      activities of peripheral blood lymphocytes did not show changes in the numbers of
      circulating natural killer (NK) cells or in the levels of NK and lymphokine
      activated killer (LAK) cytolytic activities. This regimen of IL-2 and IFN alpha
      2a with 5-FU has only modest anti-tumour activity in advanced colorectal cancer.

PMID- 8980408
TI  - Pain and other symptoms during the first year after radical and conservative
      surgery for breast cancer.
AB  - This study assessed pain, neurological symptoms, oedema of the ipsilateral arm,
      anxiety and depression occurring in women treated surgically for breast cancer,
      the impact of these symptoms on daily life and how they evolved during the 1 year
      follow-up. Ninety-three consecutive patients with non-metastasised breast cancer
      who were treated during 1993-94 were examined before surgery and after 1, 6 and
      12 months. They were asked about pain, neurological symptoms and oedema in the
      breast scar region and/or ipsilateral arm. Sensory testing was performed, and
      gripping force and the circumference of the arm were measured. Anxiety and
      depression were evaluated. One year after surgery, 80% of the women had treatment
      related symptoms in the breast scar region and virtually all patients had
      symptoms in the ipsilateral arm. The incidence of chronic post-treatment pain was
      higher after conservative surgery than after radical surgery (breast area: 33% vs
      17%, NS; ipsilateral arm: 23% vs 13%, NS). Numbness occurred in 75% and oedema of
      the ipsilateral arm in over 30% of the patients after both radical and
      conservative surgery. Phantom sensations in the breast were reported by 25% of
      the patients. No difference in psychic morbidity was detected after the two types
      of surgery. Both the anxiety and depression scores were highest before surgery,
      decreasing with time, and were significantly correlated with preoperative
      stressful events.

PMID- 8980409
TI  - Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier
      solution.
AB  - A novel peritoneal carrier solution, Icodextrin 20 (7.5%), has allowed
      exploration of prolonged, intraperitoneal (i.p.) infusion of the cytotoxic drug 5
      fluorouracil (5-FU). A phase I and pharmacokinetic study was performed to
      determine the toxicities and maximum tolerated dose of prolonged and continuous
      intraperitoneal 5-FU in patients with peritoneal carcinomatosis. Seventeen
      patients were entered into this study. Each patient had a Tenckhoff catheter
      placed into the peritoneal cavity under general anaesthetic. After initial
      flushing and gradual increase in exchange volumes with Icodextrin 20, 5-FU was
      administered daily from Monday to Friday, 50% as a bolus in the exchange bag and
      50% in an elastomeric infusor device delivering continuous 5-FU to the peritoneal
      cavity at 2 ml h-1. Treatment was continued for 12 weeks or until intolerable
      toxicity developed. Abdominal pain and infective peritonitis proved to be the
      main dose-limiting toxicities. Initial problems with infective peritonitis were
      overcome by redesign of the delivery system, and it proved possible to deliver
      300 mg m-2 5-FU daily (5 days per week) for 12 weeks. Pharmacokinetic studies
      showed i.p. steady-state 5-FU concentrations (mean 47 500 ng ml-1) that were >
      1000-fold higher than systemic venous levels (mean 30 ng ml-1).

PMID- 8980411
TI  - Effects of interstimulus interval on somatosensory evoked magnetic fields (SEFs):
      a hypothesis concerning SEF generation at the primary sensorimotor cortex.
AB  - Cerebral responses evoked by peripheral stimuli are known to depend critically on
      the interstimulus interval (ISI). Here we report on the effects of ISI on
      somatosensory evoked magnetic fields (SEFs) to right median nerve stimulation,
      obtained in 9 healthy adults with ISIs of 0.15 0.3, 1,3 and 5 s. At the
      contralateral (left) primary sensorimotor cortex (SMI), the first cortical
      response, N20m, was stable between the ISIs 0.3 and 5 s, but slightly attenuated
      at the shortest ISI of 0.15 s. In contrast, the P35m and P60m deflections were
      very sensitive to changes of the ISI, declining steadily with shortening of the
      ISI throughout the entire range. These deflections were frequently undetectable
      at the shortest ISI of 0.15 s. Concomitant with the reductions of P35m and P60m,
      an N45m deflection was enhanced toward the short ISIs. Responses from second
      somatosensory cortex (SII) and posterior parietal cortex (PPC) were seen only
      with ISIs of 1 s or greater, being strongest at the 5 s ISI. Based on known
      effects of the ISI on intracellular evoked potentials, we present the following
      tentative model for the generation mechanism of the SMI response: N20m represents
      early excitatory postsynaptic potentials (EPSPs), P35m early inhibitory
      postsynaptic potentials (IPSPs), N45m secondary EPSPs and P60m late IPSPs in
      pyramidal neurones of area 3b. For practical purposes, SEFs from SMI can be
      obtained with short ISIs, while responses from SII and PPC require an ISI of at
      least 1 s.

PMID- 8980412
TI  - Preserved widespread N18 and progressive loss of P13/14 of median nerve SEPs in a
      patient with unilateral medial medullary syndrome.
AB  - Median nerve somatosensory evoked potentials (SEPs) in a patient with unilateral
      medial medullary syndrome of recent onset having an MRI-confirmed lesion at upper
      medulla were investigated. Cortical N20 following stimulation of the affected
      limb was extremely depressed and delayed, whereas widespread N18, which was best
      manifested by the CPi-C2S lead (CPi is centroparietal electrode ipsilateral to
      the stimulation), showed no significant difference regarding amplitude and
      duration between affected and non-affected sides. The result supported our
      previous opinion that the principal part of N18, the broad negativity lasting
      around 20 ms, originates from the cuneate nucleus at the medullary level. Less
      steep onset of N18 on the affected side suggested that some structures rostral to
      the cuneate nucleus, possibly the termination of the overall ascending volley,
      may contribute to the earliest part of N18. P13/14 on the affected side normally
      preserved at the first examination progressively declined and finally disappeared
      after 4 months, which suggested that the major part of P13/14 is generated within
      caudalmost medial lemniscus, as well as the occurrence of retrograde degeneration
      of lemniscal fibers.

PMID- 8980410
TI  - Silibinin protects against cisplatin-induced nephrotoxicity without compromising
      cisplatin or ifosfamide anti-tumour activity.
AB  - Cisplatin is one of the most active cytotoxic agents in the treatment of
      testicular cancer, but its clinical use is associated with side-effects such as
      ototoxicity, neurotoxicity and nephrotoxicity. Long-term kidney damage from
      cisplatin particularly affects the proximal tubular apparatus and can be detected
      by increased urinary excretion of brush-border enzymes, such as L-alanine
      aminopeptidase (AAP), and magnesium. In the current study, the flavonoid
      silibinin was used as a nephroprotectant for cisplatin-induced nephropathy in a
      rat animal model. Infusion of silibinin before cisplatin results in a significant
      decrease in glomerular (indicated by creatinine clearance and serum urea level)
      and tubular kidney toxicity (excretion of brush-border enzymes and magnesium).
      Silibinin given alone had no effect on renal function. In order to exclude an
      inhibition of the anti-tumour activity of cisplatin and 4-hydroperoxy-ifosfamide
      by co-administration of silibinin, in vitro studies were performed in three
      established human testicular cancer cell lines. Dose-response curves for
      cisplatin (3-30 000 nmol) combined with non-toxic silibinin doses (7.25 x 10(-6)
      or 7.25 x 10(-5) mol l-1) did not deviate significantly from those of cisplatin
      alone as measured by relative cell survival during a 5 day assay using the
      sulphorhodamine-B staining technique. Also silibinin did not influence the
      cytotoxic activity of 4-hydroperoxy-ifosfamide (30-10 000 nmol) in vitro. In
      summary, these in vitro data rule out a significant inhibition of the anti-tumour
      activity of the major nephrotoxic components, cisplatin and 4-hydroperoxy
      ifosfamide, by co-administration of silibinin in a human germ cell tumour cell
      line model. Together with these demonstrated cytoprotection effects in the rat
      animal model, these data form the basis for a randomised clinical trial of
      silibinin for the protection of cisplatin-associated nephrotoxicity in patients
      with testicular cancer.

PMID- 8980413
TI  - Somatosensory evoked potentials recorded from the posterior pharynx to
      stimulation of the median nerve and cauda equina.
AB  - Somatosensory evoked potentials (ppSEPs) in response to stimulation of the median
      nerve at the wrist and the cauda equina at the epidural space (the L4 level) were
      recorded from the posterior wall of the pharynx in 15 patients who underwent
      spinal surgery under general anesthesia, using disc electrodes attached to the
      endotracheal tube, and compared with segmental spinal cord potentials (seg-SCPs)
      that were recorded simultaneously from the posterior epidural space (PES). ppSEPs
      consisted of the initially positive spike (P9) followed by slow positive (P13)
      and negative (N22) waves. The P13 and N22 of ppSEPs had phase reversal
      relationship with the P2 and N2 recorded from the PES, respectively. The peak
      latencies of P9 (9.40 +/- 0.7 ms) (mean +/- SD), P13 (13.1 +/- 0.9 ms), and N22
      (22.0 +/- 2.1 ms) of ppSEPs coincided with those of P1, N1 and P2 of seg-SCPs,
      respectively, ppSEPs were recorded more clearly with a reference electrode on the
      dorsal surface of the neck than with the reference electrode at the earlobe or
      back of the hand. The threshold and maximal stimulus intensities were also
      similar between the ppSEPs and seg-SCPs. Thus, the P9, P13, and N22 components of
      ppSEPs were thought to have the same origin as the P1, N1 and P2 of seg-SCPs,
      respectively. Therefore, the P9, P13 and N22 of ppSEPs may reflect incoming
      volleys through the root, synchronized activities of the interneurons and primary
      afferent depolarizations (PAD), respectively. ppSEPs in response to cauda equina
      stimulation showed that the latencies of the two initial components (4.6 +/- 0.4
      and 6.4 +/- 0.6 ms) corresponded to those of the SCPs recorded from the PES (4.6
      +/- 0.3 and 6.3 +/- 0.5 ms), suggesting that these potentials reflect impulses
      conducting through the spinal cord, similar to epidurally recorded SCPs.

PMID- 8980414
TI  - Acute hypothyroidism leads to reversible alterations in central nervous system as
      revealed by somatosensory evoked potentials.
AB  - Although functional alterations in the central nervous system (CNS) and
      peripheral nerves are well documented in overt hypothyroidism, little is known
      about alterations of CNS in acute hypothyroidism. Sixteen patients with
      differentiated thyroid carcinoma were studied when prepared for radioiodine
      scanning after stopping levothyroxine (L-T4) therapy for 6 weeks to determine
      whether acute hypothyroidism leads to alteration in somatosensory evoked
      potentials (SSEPs). Repeat SSEPs were performed on the same patients at 6 months
      following L-T4 therapy when patients were euthyroid. Neurophysiological findings
      were compared with a group of 20 normal controls with no history of thyroid
      disease. Peripheral and central conduction in the median and tibial nerve
      stimulated SSEPs studied. A significant prolongation of central conduction time
      in SSEPs was found in patients with acute hypothyroidism when compared to those
      in control subjects. Abnormal latencies were not correlated with thyroid hormone
      levels. These neurophysiologic abnormalities were completely restored to normal
      at 6 months after L-T4 therapy. We conclude that acute hypothyroidism leads to
      reversible alterations in CNS as determined by SSEP recordings. Our results also
      suggest that SSEPs could be useful tests to monitor functional alteration of the
      CNS in acute hypothyroidism.

PMID- 8980415
TI  - Binaural interaction and the effects of stimulus intensity and repetition rate in
      human auditory brain-stem.
AB  - Binaural interaction (BI) components in brain-stem auditory evoked potential
      (BAEP) and their changes with stimulus intensity and repetition rate were
      examined in human adult. Seven BI components were identified, which occurred
      between the latency range of 5 and 11 ms and coincided consistently with the
      latency range of BAEP waves IV-VII. Waves DV and DVII, occurring at the
      downslopes of BAEP waves V and VII, respectively, were the two most prominent and
      reproducible BI components. Wave DVII existed consistently at high, moderate and,
      in most cases, low stimulus intensities, suggesting that this component is
      neurogenic although acoustic cross-talk may account for a part of its waveform at
      high stimulus intensities. The latencies of all BI components increased as a
      function of decreasing stimulus intensity, while the interpeak intervals,
      especially DV-DVII, were essentially constant at different intensity levels. The
      amplitudes of BI components decreased slightly with decreasing intensity. As
      click repetition rate increased, BI wave latencies and interpeak intervals
      increased slightly and amplitudes decreased slightly. When repetition rate
      increased to above 20/s, BI components became poorly differentiated. Lower
      repetition rates, e.g. 10/s, are therefore preferred for routine derivation of
      the BI. The changes in the latency and amplitude of BI components with stimulus
      intensity and repetition rate were associated or concomitant with those of the
      corresponding BAEP components in monaural and binaural potentials. In view of the
      concomitant relationship between BI and BAEP latency, we designate BI components
      in association with the corresponding BAEP components.

PMID- 8980416
TI  - The influence of stimulus intensity and inter-stimulus interval on the detection
      of pitch and loudness changes.
AB  - This study illuminates processes underlying change detection for different
      features (detection of pitch versus loudness changes) and different amounts of
      attentional allocation (automatic versus attentive change detection). For this
      reason, the influence of important stimulus characteristics (intensity and inter
      stimulus interval (ISI)) on these different types of change detection was
      determined. By varying intensity, it should be clarified whether these processes
      are mainly sensitive to the informational content of the change or to the total
      amount of stimulus energy. By varying ISI, it should be determined whether they
      are differentially sensitive to manipulations of encoding time and/or state of
      sensory refractoriness. Automatic change detection was indexed by the mismatch
      negativity (MMN), which is a component of the event-related brain potential
      (ERP). Attentive change detection was indexed by the N2b and P3 components of the
      ERP and by behavioral performance. Human subjects were presented with a high
      probability standard tone and a low-probability deviant-tone, which differed from
      the standard tone in frequency (Experiment I) or intensity (Experiment II). In
      separate blocks, the intensities of the standard stimuli were of 55 and 70 dB SPL
      and ISIs were of 350 and 950 ms. During the first part of the experiments,
      subjects were engaged in silent reading, whereas they tried to discriminate
      deviants from standards in the second part. The MMN elicited by a frequency
      change was invariant to variations in intensity and ISI, whereas the MMN elicited
      by an intensity change was significantly modulated by both intensity and ISI.
      This implies functional differences between the neural traces underlying the
      frequency-MMN and the intensity-MMN. In addition, there were larger effects of
      the ISI on the N2b and P3 amplitudes as compared with the effects on the MMN
      amplitudes, suggesting stronger capacity limitations for attentive change
      detection than for automatic change detection.

PMID- 8980418
TI  - Properties of auditory brainstem responses evoked by intra-operative electrical
      stimulation of the cochlear nucleus in human subjects.
AB  - Electrically evoked auditory brainstem response (EABR) testing can aid placement
      of the stimulating electrodes during surgical implantation of an auditory
      brainstem implant (ABI). To facilitate efficient testing, this study of EABR
      properties examined the effects of various stimulating and recording parameters
      on the magnitude and clarity of the EABRs obtained from 9 successive ABI patients
      during intra-operative monitoring. Both stimulus polarities elicited EABRs; the
      response waveforms were similar and no significant differences between the
      latencies were found. Stimulus-response relationships displayed thresholds and
      non-linear growth, characteristic of neural activity, and provided a stimulus
      amplitude that elicited readily detectable EABRs in all subjects. The stimulus
      rate could be increased without degrading the EABRs, but usually 50 Hz was used
      with a 10 ms sampling sweep so that muscle responses, which occurred later than
      EABRs, could be detected. When 3 stimulating electrodes in a line were tested,
      the pair with the largest separation consistently provided the largest response.
      A recording filter passband of 10-3000 Hz was useful for attenuating interference
      signals because there is negligible energy in the EABR at frequencies above 3
      kHz, but there is some energy below 100 Hz.

PMID- 8980417
TI  - Intensity dependence of auditory evoked potentials in behaving cats.
AB  - The intensity dependence of auditory evoked potentials (AEPs) recorded epidurally
      over the primary (AI) and secondary (AII) areas of the auditory cortex was
      studied in behaving cats during wakefulness, sleep and anesthesia. Four kHz tones
      of 50, 60, 70, and 80 dB SPL, presented in random order every 2 +/- 0.2 s by a
      bone conductor, elicited clear changes of the AEP amplitudes with increasing
      stimulus intensity, but individual components displayed different response
      curves. AEP components from the AI region showed saturation of their amplitude
      with stimulus intensity (P13, P34) or no amplitude increase (N19), while
      amplitude and intensity were linearly related in the AII area. The intensity
      dependence of the first positive component (P12/P13) was consistently stronger
      for the AEP recorded from the AI than from the AII area, while later components
      exhibited no difference between AI and AII. During slow wave sleep, the intensity
      dependence of this first positive component increased in the two areas, while
      that of later components decreased. Pentobarbital anesthesia abolished almost all
      later components and depressed the intensity dependence of the first positive
      component both in the AI and AII area. These results indicate that (I) clear
      intensity dependence of AEP exists in the cat auditory cortex and (2) this
      intensity dependence, especially that of the first positive AEP component, shares
      functional similarities to the human augmenting/reducing phenomenon in the
      auditory modality concerning regional differences and sleep-waking cycle.

PMID- 8980419
TI  - Short-term replicability of the mismatch negativity.
AB  - The short-term replicability of the mismatch negativity (MMN) between two
      recording sessions spaced 2 h apart was evaluated at individual and group levels
      in a sample of 11 healthy adults. Subjects were presented with a random sequence
      of 1000 Hz standard (92%) and 1100 Hz deviant (8%) tones while they were reading
      a book. The N1 and P2 exogenous components to standard tones showed a fairly good
      individual and group replicability. There were no significant differences in the
      MMN amplitude and latency between the two sessions in the group of subjects as a
      whole. The individual replicability of the MMN was not as good as for the N1 to
      standards, reaching significance in only some of the electrodes. This result was,
      however, similar to that obtained for the N1 after deviant tones. The results
      indicate that the MMN has good replicability at the group level, and further that
      at the individual level, MMN replicability is similar to that of the N1 to
      deviants. This suggests that the number of summations should be increased in
      order to improve the clinical usefulness of the MMN.

PMID- 8980421
TI  - Event-related potentials in the dorsal hippocampus of rats during an auditory
      discrimination paradigm.
AB  - The relation of the hippocampal neuronal activity to the rat event-related
      potential (ERP) generation was examined during an auditory discrimination oddball
      paradigm. ERPs were recorded using a linearly-arranged series of electrodes
      chronically implanted at the skull, in the frontoparietal cortex, in the CA1 and
      CA3 regions of the dorsal hippocampus and in the thalamus. The target tone
      elicited N40, P100, N200, and P450 at the skull electrode. The non-target tone,
      on the other hand, prominently evoked only the P100 component. At the
      intracranial electrodes, the ERP amplitude at the latency of the skull P450 was
      significantly greater in the CA3 region than that at other recording sites,
      although a phase reversal was not observed. The results indicate that the P450 of
      the rat may correspond to the human P3, and that the neuronal activity in the
      hippocampus is involved in its generation.

PMID- 8980420
TI  - P300, probability, and the three-tone paradigm.
AB  - The effects of stimulus probability on P300 from a 3-tone paradigm were examined
      in two experiments. Experiment 1 manipulated the probability of the non-target
      tone as 0.10, 0.45, or 0.80, while the target tone probability was always 0.10.
      Experiment 2 manipulated the probability of 3 tones as 0.10, 0.30, or 0.60, with
      one of the infrequent tones assigned as the target in each condition. Subjects
      were required to press a button in response to the target stimulus in both
      experiments. The results indicated that the P300 to the target and the non-target
      were both affected by the probability of the eliciting stimulus, such that
      component amplitude was inversely related to probability; no reliable P300
      latency effects were found. Target tones elicited larger P300 amplitude than the
      non-target tones at the same probability. The findings suggest that probability
      effects on P300 amplitude are independent of responding to a specific target
      stimulus and are discussed with reference to the clinical utility of the 3-tone
      paradigm.

PMID- 8980422
TI  - Instantaneous frequency maps, dipole models and potential distributions of
      pattern reversal-evoked potential fields for correct recognition of stimulated
      hemiretinae.
AB  - Lateral hemifield pattern-reversal visual evoked potential (PVEP) field data were
      evaluated using potential distributions, dipole modelling and distributions of
      Hilbert transformation-based instantaneous frequency in order to determine the
      stimulated hemisphere. Twenty channel records were collected from 35 normal
      volunteers in two laboratories using similar stimulus conditions (11-20.5 degrees
      target, 60-75 min checks, 2/s reversal, 500 ms analysis epoch). P100 latency was
      determined in each average by the global field power maximum between 90 and 120
      ms. Using the data from O1 and O2 at P100 latency, the stimulated hemisphere was
      identified by maximal potential or minimal instantaneous frequency on the
      stimulus-contralateral side, or, using the 20-electrodes data at P100 by the
      ipsilateral lateralization of the dipole model. Correct classification of the
      stimulated 70 hemiretinae was achieved by potential distribution in 44 cases, by
      dipole modelling in 54 cases and by instantaneous frequencies in 68 cases. Errors
      in the classification by potential distribution and dipole location were twice as
      frequent for decisions based on expected locations over the left than over the
      right hemisphere. This finding might be caused by the relatively larger size of
      the left occipital lobe. We conclude that a single value of instantaneous
      frequency which implies a massive data reduction can serve as a robust parameter
      for the characterization of the input conditions of hemifield PVEP (i.e. the
      stimulated hemiretina). It is more successful than potential distribution or
      dipole modelling, probably because instantaneous frequency incorporates
      considerably more information than the other two measures. It is suggested to
      explore instantaneous frequency as a parameter to recognize small retinal area
      stimuli in perimetry studies.

PMID- 8980423
TI  - P300, stimulus intensity, and modality.
AB  - Auditory and visual stimulus intensity levels were manipulated systematically in
      separate conditions to assess the influence of these variables on the P300 event
      related brain potential (ERP). Increases in stimulus intensity produced increases
      in P300 amplitude and decreases in peak latency for both modalities, although the
      latency effects were stronger for visual stimulation. Similar, somewhat weaker
      stimulus intensity effects also were observed for the N100, P200, and N200
      components. The findings suggest that stimulus intensity contributes to both P300
      amplitude and latency measures in important ways and are discussed in relation to
      the use of ERPs in applied contexts.

PMID- 8980424
TI  - Asymptomatic carotid stenosis--looking for a sensible strategy.

PMID- 8980425
TI  - Pathogenesis of abdominal aortic aneurysms--cellular and biochemical mechanisms.

PMID- 8980426
TI  - The importance of transesophageal echocardiography during surgery of the thoracic
      aorta.
AB  - OBJECTIVES: To assess left ventricular dimensions and cardiac output during
      thoracic and thoracoabdominal aortic aneurysm repair. MATERIAL AND METHODS: Nine
      patients undergoing thoracic and thoracoabdominal aneurysm repair using direct
      cross-clamping without shunt or by-pass were studied prospectively. Prior to,
      during cross-clamping (XC) and after declamping left ventricular cross-sectional
      areas were monitored with transesophageal echocardiography. A pulmonary artery
      catheter was used for measurements of cardiac output with the thermodilution
      technique. RESULTS: Cardiac output increased 43% from baseline during XC (p <
      0.01) and was still 55% above baseline at declamping (p < 0.05). Left ventricular
      end-systolic inner area was reduced 32% during XC (p < 0.01). Pulmonary artery
      pressures and central venous pressure increased during declamping (p < 0.05).
      Heart rate increased 38% from 66 beats/ min to 92 beats/min (p < 0.01) and was
      still 30% elevated at declamping (p < 0.01). CONCLUSION: During thoracic aortic
      XC, cardiac output is increased and left ventricular end-systolic dimension is
      reduced. TEE is a valuable supplement to pressure measurements for the evaluation
      of cardiac function during surgery of the thoracic aorta.

PMID- 8980427
TI  - Intraoperative transcranial Doppler sonography monitoring during carotid surgery
      under locoregional anaesthesia.
AB  - OBJECTIVES: Studies comparing transcranial Doppler ultrasonography (TCD) with
      other intraoperative monitoring techniques for detecting clamping ischaemia
      during carotid endarterectomy under general anaesthesia suggest that a reduction
      of > two-thirds in the mean middle cerebral artery velocity (mMCAv) or a
      reduction of > 0.4 in the preclamping mMCAv: clamping mMCAv ratio warrants
      cerebral protection. Our aim was to study the relationship between mMCAvs and
      clamping ischaemia during carotid endarterectomy in awake patients. MATERIALS AND
      METHODS: In a consecutive series of 57 patients undergoing carotid endarterectomy
      under locoregional anaesthesia 51 were monitored by intraoperative TCD,
      continuous EEG, and neurologic awake testing. RESULTS: Five of the 51 (9.8%)
      patients had transient clamping ischaemia, which carotid shunting reversed. TCD
      showed that these five patients had significant lower mean mMCAvs than the other
      46 patients, who had no deficits (1.8 +/- 1.1 cm/s vs. 26.2 +/- 8.5, p = 0.0003).
      Current TCD criteria indicated that four other patients (7.8%) should have been
      shunted. All four had significantly higher clamping mMCAvs than the five shunted
      patients (11.5 +/- 1.9 vs. 1.8 +/- 1.1, p = 0.0012). CONCLUSIONS: Intraoperative
      TCD detected cerebral ischaemia and yielded no false-negative. An mMCAv of 10
      cm/s or less may indicate the risk of clamping ischaemia better than the higher
      threshold currently proposed. This would avoid unnecessary shunting due to false
      positives.

PMID- 8980428
TI  - Infrared optoelectronic volumetry, the ideal way to measure limb volume.
AB  - OBJECTIVES: The aim of the study was to compare a novel infrared optoelectronic
      system (Perometer) of limb volume measurement with water displacement and two
      indirect measurement techniques. DESIGN: A prospective experimental study.
      METHODS: In 10 healthy male volunteers (20 limbs) we compared limb volume
      measurements obtained by water displacement, infrared perometry, the disc model
      method and the frustrum method. In a further 17 patients with swollen limbs due
      to lymphatic (9 limbs) or venous (11 limbs) disease, perometry was compared to
      the disc model method and the frustrum method only. RESULTS: In normal limbs,
      mean +/- S.D. limb volume using water displacement was 1802 +/- 268 ml. Perometer
      values agreed almost exactly (1809 +/- 262 ml, r = 0.97, variation +/- 7% by
      limits of agreement) but both the disc (1923 +/- 306 ml, r = 0.90, variation +/-
      14%) and frustrum (1905 +/- 372 ml, r = 0.72, variation +/- 28%) methods
      significantly overestimated limb volumes (p < 0.05 (ANOVA, Fisher's Least
      Significant Difference)). In diseased limbs perometer, disc method and frustrum
      method results were 2415 +/- 995 ml, 2494 +/- 969 ml, and 2413 +/- 870 ml
      representing variation of +/- 17% and +/- 23% for disc method and frustrum method
      respectively compared to perometry. CONCLUSIONS: Perometry is a novel, extremely
      accurate and easy method for assessing limb volume. It provides more accurate
      results than traditional indirect measurement of limb volume and potentially is a
      very useful clinical and research tool.

PMID- 8980429
TI  - Evaluation of femoropopliteal arteries with duplex ultrasound after angioplasty.
      Can we predict results at one year?
AB  - OBJECTIVES: To determine if Duplex ultrasound (DUS) 1 day after percutaneous
      transluminal angioplasty (PTA) is prognostic for haemodynamic and clinical
      results at 1 year. DESIGN: Prospective study. PATIENTS AND METHODS: Thirty-four
      femoropopliteal artery segments were treated with PTA. The peak systolic velocity
      ratio (PSV ratio = PSV in stenosis: PSV in normal segment) was determined with
      DUS before PTA, 1 day after PTA and 1 year after PTA. Clinical results were
      assessed with the SVS/ISCVS (Society for Vascular Surgery/International Society
      for CardioVascular Surgery) results classification. RESULTS: A 1 year, clinical
      benefit from PTA was seen in 16 of 25 patients (64%) and haemodynamic improvement
      in 20 of 34 treated segments (59%). With DUS three residual stenoses were found 1
      day after PTA; all occluded within 1 year. Segments with good DUS results after
      PTA showed haemodynamic deterioration in 30%. Clinical improvement was seen in
      most patients with DUS improvement, whereas no change or deterioration was found
      in patients with both good and poor DUS results at 1 year. CONCLUSIONS: Residual
      stenosis on DUS 1 day after PTA is prognostic for failure within 1 year. However,
      good DUS results after PTA cannot predict haemodynamic success. Haemodynamic
      success at 1 year does not imply clinical success.

PMID- 8980430
TI  - A ten year audit of surgery for vascular trauma in a British teaching hospital.
AB  - Vascular trauma is uncommon in the U.K. with the exception of Northern Ireland.
      In marked contrast to North America, gunshot wounds are rare and stabbings are
      infrequent. A 10 year audit was carried out in a regional vascular referral unit
      to determine the mechanisms, treatment and outcome of vascular injuries. Forty
      seven patients were operated on during the period. The median age was 26 years
      (range 7-85 years); two-thirds were men. Road traffic accidents accounted for 21
      (45%) of injuries, other accidents 15 (32%) and stabbings 11 (23%). There were no
      gunshot wounds. Most injuries were penetrating with no associated fracture.
      Commonly injured vessels were the brachial (30%) and superficial femoral (15%)
      arteries. Fifty-three primary operations were performed, 10 were vein
      interpositions and 21 were bypass grafts. There were three primary amputations
      (6%). Eleven patients suffered a complication including one death. One graft
      occluded requiring a further bypass. Two patients required fasciotomy as a
      secondary procedure. Median follow-up was 6 months. Eighty-one percent of
      patients were symptom free at last follow-up. There were no late vascular
      complications. Our experience is likely to represent that of other vascular units
      in countries with strict gun control legislation, little civil violence and
      modest levels of road traffic accidents.

PMID- 8980431
TI  - The myth of the second prophylactic antibiotic dose in aortoiliac
      reconstructions.
AB  - OBJECTIVES: To determine whether a prophylactic second dose of antibiotics is
      justified when severe blood loss and/or prolonged operation time occurs during
      aortoiliac reconstructions. METHODS: We measured the cefuroxime concentration in
      venous blood serum and subcutaneous fat tissue of 30 patients who underwent
      elective aortoiliac reconstruction after a single intravenous dose of 1500 mg
      cefuroxime. RESULTS: The mean blood loss was 1912 ml (range 200-7000). The mean
      operation time was 212 min (range 70-330). The cefuroxime concentration in blood
      serum 30 min after the gift varied from 53.7-561.6 mg/l and during closure of the
      abdominal incision from 13.2-90.0 mg/l. Taking the minimum inhibitory
      concentration for Staphylococcus species as 1.0 mg/l, we found an adequate
      prophylactic serum cefuroxime concentration in all patients. There was a
      statistically significant correlation between serum cefuroxime concentration and
      blood loss (p = 0.01) and operation time (p = 0.0001). CONCLUSIONS: Although
      serum concentration of cefuroxime is greatly influenced by blood loss and
      operation time, a second dose of cefuroxime in aortoiliac reconstructions is not
      necessary if the operation is completed within 5.5 h and if perioperative blood
      loss does not exceed 7000 ml.

PMID- 8980432
TI  - Subclavian carotid transposition: an analysis of a clinical series and a review
      of the literature.
AB  - OBJECTIVE: To analyse the clinical results and long-term patency rates of 108
      patients with subclavian carotid transposition (SCT) and compare the outcomes to
      other clinical series using the same technique, as well as to those reported for
      other surgical procedures and PTA in the treatment of proximal subclavian artery
      disease. METHODS: The hospital records of 108 patients with carotid subclavian
      transposition were retrospectively reviewed for preoperative symptoms, Doppler
      examination, arteriography, blood pressure differentials and postoperative
      complications. Long-term patency and symptoms were determined during a follow-up
      examination including a history, physical examination, blood pressure
      differentials, Doppler examinations and arteriography in selected cases. RESULTS:
      The indication for SCT were subclavian steal (78%), upper extremity ischaemia
      (59%), rest pain or acral necrosis (5%), vertigo (6%). There was no mortality,
      blood pressure differentials were equalised in all patients without any early
      reocclusions. The complication rate was 15% with a permanent morbidity of 3%.
      Eighty-four patients (77%) could be re-examined during follow-up. For them the
      overall patency after a mean observation period of 70 months (1-144 months) was
      100%. CONCLUSIONS: Subclavian carotid transposition is an excellent method for
      the treatment of proximal subclavian occlusive disease because of its exceptional
      long-term patency and low morbidity.

PMID- 8980433
TI  - Femorofemoral crossover grafts for claudication: a safe and reliable procedure.
AB  - OBJECTIVE: To evaluate the role of femorofemoral crossover grafts in patients
      with disabling claudication. DESIGN: Retrospective study. SETTING: University
      hospital. MATERIALS: Two hundred and eleven patients with iliac artery disease
      undergoing femorofemoral crossover grafts for disabling claudication. CHIEF
      OUTCOME MEASURES: Perioperative mortality, follow-up cumulative graft patency,
      limb loss, survival, graft infection and false aneurysm formation were evaluated
      to determine the immediate and long-term outcome of the procedure. MAIN RESULTS:
      Primary and secondary graft patency at 5 years was 72% and 89% respectively.
      There were no perioperative deaths (zero 30 day mortality). Dacron was used in 66
      patients (31%) and PTFE in 145 (69%). There were no differences in patency
      between the two graft materials but eight Dacron grafts (12.1%) were removed
      because of complications (false aneurysm or infection) compared to four PTFE
      grafts (2.7%) (p < 0.001 Chi-square). Five patients (2%) have undergone a major
      lower limb amputation. Forty-one patients (19%) have required subsequent inflow
      procedures which represents a cumulative need for inflow of 5% per year.
      CONCLUSIONS: Femorofemoral crossover grafts are a safe and reliable procedure in
      patients with disabling claudication caused by unilateral iliac artery disease.

PMID- 8980434
TI  - Neovascularisation is the principal cause of varicose vein recurrence: results of
      a randomised trial of stripping the long saphenous vein.
AB  - OBJECTIVES: To determine whether routine stripping of the long saphenous vein
      reduces recurrence after varicose vein surgery. DESIGN: Randomised controlled
      trial. All operations done by a consultant vascular surgeon. Two year follow-up.
      MATERIALS AND METHODS: One hundred patients with primary long saphenous varicose
      veins (133 legs) were randomised. Two year follow-up in 81 patients (113 legs)
      with questionnaire, clinical examination and Duplex scanning. RESULTS: Some 89%
      remained satisfied with the results of their surgery, though 35% had recurrent
      veins on clinical examination. Recurrence was reduced from 43 to 25% in patients
      who had their long saphenous vein stripped (p = 0.04, chi 2). Neovascularisation
      (serpentine tributaries arising from the ligated saphenofemoral junction) was
      detected in 52% of limbs and was the commonest cause of recurrence. Most
      tributaries were less than 3 mm in diameter and only caused recurrence if the
      long saphenous vein or a major thigh vein was intact. Twelve patients had
      tributaries greater than 3 mm diameter and all had recurrent varicose veins.
      CONCLUSIONS: Recurrence is common after varicose vein surgery and in this study
      was caused principally by neovascularisation at the ligated saphenofemoral
      junction. Clinical recurrence is reduced by routine stripping of the long
      saphenous vein.

PMID- 8980435
TI  - Increasing incidence of aneurysms of the abdominal aorta in The Netherlands.
AB  - OBJECTIVES: To study the trend in incidence of aneurysms of the abdominal aorta
      in The Netherlands during the past two decades. SETTING: The Dutch population
      from 1972 to 1992. DESIGN: Analysis of all hospital admissions and deaths due to
      aneurysms of the abdominal aorta. OUTCOME MEASURES: Age adjusted and age specific
      mortality and discharge rates. In-hospital mortality after surgery upon aneurysms
      of the abdominal aorta. RESULTS: From 1972 to 1992 age adjusted mortality from
      aneurysms of the abdominal aorta rose from 3.1 to 8.1 per 100,000 in men, and
      from 1.4 to 2.2 in women. Age adjusted discharge rates (alive and dead) for non
      ruptured abdominal aortic aneurysms increased from 3.7 to 37.6 per 100,000 in men
      and from 1.2 to 5.5 in women. For ruptured aneurysms, the age adjusted discharge
      rates increased from 2.4 to 10.3 per 100,000 in men and from 0.7 to 1.7 in women.
      Age adjusted in-hospital mortality after surgery upon non-ruptured aneurysms was
      halved from 13% in 1972 to 7% in 1992, mortality after acute repair upon ruptured
      aneurysms also decreased from 52% in 1972 to 36% in 1992. CONCLUSIONS: There was
      an impressive increase in the hospital based incidence for aneurysms of the
      abdominal aorta during the past two decades in The Netherlands. An improved
      detection rate through ultrasound is probably a major contributor to this
      increase, but gender differences and the rise in the number of ruptured aneurysms
      suggest that a real increase in incidence may exist, especially in men. Surgical
      outcome for both ruptured and non-ruptured aneurysms of the abdominal aorta
      improved.

PMID- 8980436
TI  - Can lower limb vascular reconstruction be based on colour Duplex imaging alone?
AB  - OBJECTIVES: To determine the safety and efficacy of Duplex scanning as the only
      imaging modality prior to lower limb vascular reconstruction. DESIGN:
      Retrospective review. SETTING: A single university vascular unit. PATIENTS AND
      METHODS: Review of all lower limb vascular reconstructions over a 2 year period.
      RESULTS: Eighty-five limbs underwent vascular reconstruction based on colour
      Duplex alone. A wide range of revascularising operations were performed,
      including 29 cases of infragenicular reconstruction. In the latter cases, the
      findings of Duplex scanning were confirmed by on table pre-reconstruction
      angiography in 28 cases and the graft occlusion rate in the first month was 14%.
      There were no postoperative complications that could be attributed to a failure
      of preoperative Duplex imaging. CONCLUSION: Vascular reconstruction can be
      undertaken safely in patients with lower limb arterial disease on the basis of
      Duplex scanning alone.

PMID- 8980437
TI  - The generation of byproducts of lipid peroxidation following carotid
      endarterectomy.
AB  - The aim of this study was to determine whether free radical-induced lipid
      peroxidation occurs following transient carotid clamping. Jugular vein plasma
      levels of malondialdehyde (MDA) and diene conjugates (DC) were estimated in 24
      patients undergoing carotid endarterectomy, at the beginning of the operation
      (To), just prior to clamping the carotid artery before the shunt was removed for
      closure of the arteriotomy (Ts), and at 30 (T30), 60 (T60), 120 (T120), 180
      (T180) and 300 (T300) seconds after the clamps were released. Carotid clamp times
      were recorded. Significant elevations in the concentrations of both MDA and DC
      were observed at T60 after clamp release (MDA = 559 +/- 64 pmol/ml, DC = 428 +/-
      32 units/ml), in comparison to concentrations at To (MDA = 408 +/- 34 pmol/ml, p
      < 0.01; DC = 374 +/- 28 units/ml, p < 0.05), returning to baseline at T300. There
      was a significant correlation between the percentage rise in MDA concentration
      and the duration of clamp-induced ischaemia (r = 0.45, p = 0.03). The
      significance of this burst of MDA and DC is unclear especially as the one patient
      who sustained a postoperative neurological deficit displayed no rise in the
      concentration of either. If this rise is related to free radical generation
      following ischaemia-reperfusion injury it may play an important role in
      influencing the clinical outcome in the patients.

PMID- 8980438
TI  - Adjusting outcome measurements for case-mix in a vascular surgical register--is
      it possible and desirable?
AB  - OBJECTIVE: We analysed the variation in the outcome of infrainguinal bypass
      surgery between departments in a register for clinical audit to see if variation
      in case-mix influenced the results. MATERIALS AND METHODS: The study was a
      retrospective analysis of 764 infrainguinal bypass operations performed from 1988
      to 1990 at six Swedish surgical departments. Results were assessed at 30 days and
      at 1 year postoperatively. RESULTS: There was a significant variation (p < 0.01)
      in mortality and amputation rates both at 30 days and at 1 year and in patency
      rate at 30 days. There were also differences in case-mix. Differences were found
      in indication, location of distal anastomosis and graft type. Regression analysis
      found that mortality was influenced by age, diabetes and heart disease and
      patency rate by location of the distal anastomosis and graft type. When
      'hospital' was added as a variable in the regression analysis it was also found
      to be a significant indicator. CONCLUSION: Location of the distal anastomosis was
      the main factor in adjusting patency for case-mix.

PMID- 8980439
TI  - Problems related to the definition of "distal" bypass and "secondary" patency
      rates. A paper for debate.
AB  - The large variations observed in "distal" bypass patency rates and the abuse of
      life-table analysis have encouraged most Vascular Committees to develop standards
      for evaluating results. However, problems continue to persist. Some of these do
      not relate to statistical analysis but to the lack of definition of both
      secondary patency and "distal" when referring to arterial bypass grafts to the
      lower limb. We present various problems and propose some strict definitions for
      each type of infrainguinal reconstruction, based on the inflow and outflow
      levels, together with a modification of the definitions of primary assisted and
      secondary patency.

PMID- 8980440
TI  - Non-invasive assessment of arterial stenoses in angioplasty surveillance: a
      comparison with angiography.
AB  - OBJECTIVES: Comparison of non-invasive arterial measurements with angiography and
      their use for angioplasty surveillance. DESIGN: Prospective assessments of
      arterial stenoses in patients undergoing angioplasty in a 9 month surveillance
      period. MATERIALS: Fifty consecutive patients undergoing angioplasty. METHODS:
      (i) One hundred and thirty-one sets of clinical assessments, ankle brachial
      Doppler pressure indices and colour Duplex velocities and diameters were compared
      to time-matched angiographic diameter stenosis. (ii) Fifty patients undergoing
      femoropopliteal angioplasty (32 stenoses and 18 occlusions) were studied with
      ankle branchial Doppler pressure indices and colour Duplex and angiography during
      a 9 month surveillance period. RESULTS: (i) Symptoms, pulses, resting ABPI, and
      exercise ABPI showed no useful correlation with angiography. Duplex velocity
      ratio and Duplex diameters showed correlation and agreement with angiography
      respectively. (ii) On surveillance, restenosis was universal but not always
      clinically significant. Angioplasty caused a rapid improvement in ABPI and
      imaging studies which worsened at later times. ABPI did not predict clinical
      failure however, Duplex and angiography predicted all clinical failures.
      CONCLUSIONS: Restenosis should be assessed with imaging of the angioplasty site
      during angioplasty surveillance.

PMID- 8980441
TI  - Endovascular repair of residual iliac artery aneurysms following surgery for
      ruptured abdominal aortic aneurysm.
AB  - Emergency repair of ruptured abdominal aortic aneurysm continues to have a high
      mortality. Such patients require expeditious operations to repair the ruptured
      segment rather than attempts to deal with all coexisting disease. The use of
      endovascular techniques obviates the need for open surgery to repair iliac
      aneurysms. We report two patients who, after successful repair of ruptured
      abdominal aortic aneurysms, had three iliac artery aneurysms treated successfully
      by embolisation in one case and percutaneous insertion of a self expandable stent
      graft in two cases. The issues that arise from such an approach are discussed
      with a review of the literature.

PMID- 8980442
TI  - Classification and grading of chronic venous disease in the lower limbs. A
      consensus statement.

PMID- 8980443
TI  - Agenesis of the inferior vena cava.

PMID- 8980444
TI  - Unilateral lower limb hypertrophic osteoarthropathy due to aortic graft infection
      and aortoenteric fistula.

PMID- 8980445
TI  - Inferior vena cava thrombosis, aortocaval fistula and aortic aneurysm: a unique
      combination.

PMID- 8980446
TI  - Non-surgical treatment of aneurysms of bilateral persistent sciatic artery.

PMID- 8980447
TI  - Pedicled omental flaps.

PMID- 8980448
TI  - Arterial graft preservation.

PMID- 8980449
TI  - Cytokine profiles in abdominal aortic aneurysms.

PMID- 8980450
TI  - Quality of life after treatment of intermittent claudication.

PMID- 8980451
TI  - Quality of life following percutaneous transluminal angioplasty for claudication.

PMID- 8980452
TI  - Cranial nerve injuries and carotid endarterectomy.

PMID- 8980453
TI  - Quality of life in patients with intermittent claudication.

PMID- 8980454
TI  - Spinal cord stimulation.

PMID- 8980455
TI  - Blood pressure after bilateral carotid surgery.

PMID- 8980457
TI  - Where do hematopoietic stem cells come from?
AB  - The experimental model constituted by a quail embryo grafted on a chick yolk sac
      has produced undisputable evidence according to which hematopoietic stem cells
      (HSC) colonizing the blood-forming rudiments are of intraembryonic origin in
      birds. Appropriate cell culture systems now make it feasible to demonstrate that
      ontogeny of the mouse hematopoietic system also involves at least two generations
      of HSC, one formed in the yolk sac and the other in the embryo, only the latter
      having lymphoid potential. Furthermore the developmental relationships between
      endothelial and hematopoietic cells are being analyzed in the avian model. Two
      distinct endothelial lineages are detected by means of interspecific
      transplantations, a dorsal one, somitic in origin, which is purely endothelial
      and a ventral one, splanchnopleural in origin, which is associated with the
      production of hematopoietic cells.

PMID- 8980458
TI  - Activation of signaling pathways and prevention of apoptosis by cytokines in
      eosinophils.
AB  - Inhibition of apoptosis in eosinophils by cytokines such as IL-5 and GM-CSF may
      play an important role in the pathogenesis of allergic and parasitic disorders.
      Recently, there has been some progress in the understanding of the signal
      transduction pathways activated by these cytokines in eosinophils. The IL-3, IL-5
      and GM-CSF receptors share a common signal transducer that possesses no intrinsic
      kinase domain. It has been shown that eosinophil stimulation by these cytokines
      is associated with increases in tyrosine phosphorylation of several cellular
      substrates. In the past few years, there has been some progress in defining the
      tyrosine kinases that are activated by the IL-3/IL-5/GM-CSF receptor beta-subunit
      in eosinophils. This review will concentrate on this topic and on its role for
      the regulation of eosinophil apoptosis.

PMID- 8980459
TI  - Dexamethasone suppressed gene expression and production of interleukin-10 by
      human peripheral blood mononuclear cells and monocytes.
AB  - Interleukin-10 (IL-10) is known to inhibit T cell-mediated responses. IL-10 has
      also been shown to play an important pathogenetic role in allergic diseases.
      Glucocorticoid is known to inhibit the production and gene expression of many
      cytokines which induce inflammatory reactions. We examined the effect of
      dexamethasone on the gene expression and production of IL-10 by human peripheral
      blood mononuclear cells (PBMCs) and monocytes. PBMCs and monocytes from 5 healthy
      volunteers were incubated with or without dexamethasone for 1 h, then stimulated
      with 5 micrograms/ml lipopolysaccharide (LPS). Gene expression and production of
      IL-10 by human PBMCs were detected without stimulation and increased by LPS
      stimulation. Dexamethasone suppressed the gene expression and production of IL-10
      by LPS-stimulated PBMCs in a dose-dependent manner by 41.6 and 61.1% at 10(-6) M,
      respectively. Also in monocytes, the gene expression and production of IL-10 were
      detected without stimulation, increased by LPS stimulation, and significantly
      suppressed by dexamethasone by 53.1 and 61.2% at 10(-6) M, respectively. This
      suppressive effect on IL-10 gene expression was not so potent compared with its
      effect on cytokines such as IL-5. The suppression of IL-10 production by
      glucocorticoid is suggested to be one of the important mechanisms by which
      glucocorticoids suppress allergic inflammation in the treatment of allergic
      diseases.

PMID- 8980460
TI  - Influence of degraded phosphatidylserine on binding of antiphospholipid
      antibodies.
AB  - BACKGROUND: Antiphospholipid antibodies (aPL) show great heterogeneity. Different
      phospholipids, with or without protein cofactor(s), and phospholipid binding
      proteins alone have been proposed as the target molecules for aPL. In order to
      determine the influence of phospholipid degradation products on the binding of
      aPL, sera from 6 patients with the antiphospholipid syndrome were studied.
      METHODS: Fresh and aged phosphatidylserine and cardiolipin were used as coating
      reagents in solid-phase immunoassay procedures. Antibody reactivity was tested by
      enzyme-linked immunosorbent assay in the sera and in eluates from columns packed
      with polystyrene scrapings coated with either cardiolipin or phoshatidylserine.
      RESULTS: Three reaction patterns of affinity-purified antibodies were seen: (1)
      reactivity with phosphatidylserine but not with cardiolipin or degraded
      phosphatidylserine, (2) reactivity with cardiolipin and degraded
      phosphatidlyserine, and (3) reactivity with all three phospholipid antigens.
      CONCLUSIONS: Striking differences in the antiphospholipid antibody reactivity
      with cardiolipin, phosphatidylserine and degraded phosphatidylserine in the
      presence of serum proteins were observed among patients with venous
      thromboembolism. The analyses showed that the degradation of phosphatidylserine
      influences the binding of aPL in in vitro assays.

PMID- 8980461
TI  - Role of resident mast cells and macrophages in the neutrophil migration induced
      by LTB4, fMLP and C5a des arg.
AB  - In the present study, we have investigated the participation of resident
      peritoneal cells (macrophages and mast cells) in the neutrophil migration induced
      in rats by the intraperitoneal administration of LTB4, fMLP or C5a des arg. The
      intraperitoneal injection of LTB4 (10 nmol), fMLP (10 nmol) and C5a des arg
      (zymosan-activated plasma, 1 ml) caused an intense neutrophil migration compared
      to the saline control (1,000, 1,500 and 2,000%, respectively). An 83% depletion
      in the number of resident cells following peritoneal lavage reduced the LTB4
      stimulated neutrophil migration by 73.6% without affecting that caused by fMLP
      and C5a des arg. Increasing the peritoneal macrophage population (236%) by
      pretreating the cavities with thioglycollate enhanced the neutrophil migration
      induced by LTB4 (129%), but did not alter that induced by fMLP and C5a des arg.
      Similarly, reducing the population of peritoneal mast cells containing toluidine
      blue-staining granules by subchronically pretreating the cavities with compound
      48/80 diminished the LTB4-induced NM by 69% but had no effect on the responses to
      fMLP and C5a des arg. Pretreating the animals with dexamethasone strongly
      inhibited (70%) the neutrophil migration induced by the intraperitoneal injection
      of LTB4, fMLP and C5a des arg. Indomethacin, BW A4C and NDGA had no such effect.
      The incubating medium from peritoneal macrophages and mast cells stimulated with
      LTB4 induced neutrophil migration when injected into the peritoneal cavity of
      rats. This migration was strongly reduced (70%) by treating the cells with
      dexamethasone. In contrast, stimulating the cells with fMLP or C5a des arg did
      not result in the release of any promigratory activity into the incubating fluid.
      Our results suggest that LTB4 induces neutrophil migration via a mechanism
      dependent on resident mast cells and macrophages while that induced by C5a des
      arg and fMLP seems to be independent of such cellular involvement. The neutrophil
      migration induced by LTB4 is apparently mediated by factor(s) whose release is
      blocked by dexamethasone. fMLP and C5a appear to cause in vivo migration by the
      formation of a concentration gradient and by a glucocorticoid-sensitive mechanism
      different from that stimulated by LTB4.

PMID- 8980462
TI  - Existence of c-kit receptor-positive, tryptase-negative, IgE-negative cells in
      human allergic nasal mucosa: a candidate for mast cell progenitor.
AB  - The accumulation of mast cells in the allergic nasal epithelium is well known,
      yet the mechanism remains unclear. We studied whether there is a candidate for
      mast cell progenitors in the allergic nasal mucosa tissue removed at the time of
      surgery. We first confirmed that most mast cells in nasal mucosae of 10 nasal
      allergic patients had c-kit receptor by immunohistochemistry using the mirror
      sectioning technique. We then investigated whether c-kit receptor+, tryptase-,
      IgE- cells existed in nasal mucosae of 15 nasal allergic patients and 15
      nonallergic ones using sequential triple immunohistochemistry. We observed the
      area in which 1,000 to 1,100 tryptase-positive cells (mast cells) existed in both
      the subepithelial layer and the deep layer of each nasal lamina propria. The
      epithelial layer above this area was also examined. Some c-kit receptor+,
      tryptase- cells existed in the nasal mucosae of 11 patients with nasal allergy
      and of 5 patients with nonallergic rhinitis. From one to four of these cells in
      the nasal epithelium and subepithelial layer of the 4 allergic patients were IgE
      negative. In contrast, no IgE-negative cells existed in the deep layer of
      allergic nasal mucosae or in any nonallergic nasal mucosae. Our results suggest
      that mast cell progenitors, hematopoietic progenitor cells or multipotential
      blood cells exist in the allergic nasal mucosa, and may contribute to the
      increase of mast cells in the epithelium and subepithelial layer of allergic
      nasal mucosa.

PMID- 8980463
TI  - Genomic organization and polymorphisms of the major house dust mite allergen Der
      f2.
AB  - We amplified genomic DNA encoding the major house dust mite allergen, Der f2,
      from Dermatophagoides farinae by means of the polymerase chain reaction and
      cloned it into Escherichia coli. The nucleotide sequences of the amplified
      fragments were determined and compared with those of the cDNA previously
      reported. Four Der f2 genomic clones were obtained, suggesting that the genomic
      Der f2 gene had sequence polymorphisms like the cDNA clones. Each of the genomic
      clones had a single small intron. With respect to the exon sequences, two of the
      four genomic clones were identical with two cDNA clones, respectively. The others
      were combinations of the two clones. Genomic Southern blotting suggested that the
      Der f2 gene is located at one locus in the mite genome and that sequence
      substitutions were due to polymorphisms among individual mite genes.

PMID- 8980464
TI  - Role of IL-13 in CD4 T cell-dependent IgE production in atopy.
AB  - IgE isotype switching of human B cells requires physical interaction of T and B
      cells via surface molecules, and either IL-4 or IL-13 secreted by T cells. In
      this study we analyzed the role of IL-4 versus IL-13 in IgE production in atopy.
      We found that peripheral blood mononuclear cells (PBMC) from atopic individuals
      but not from nonatopic subjects secreted IgE without addition of IL-4 or IL-13,
      if T and B cells were simultaneously activated by anti-CD3 mAb and soluble CD40L,
      respectively. IgE production by atopic PBMC was dependent on endogenously
      secreted IL-4 and IL-13, since it could be blocked by a combination of anti-IL-4
      plus anti-IL-13 antibodies. No differences in the B cell compartment of
      nonatopics and atopics were detectable, since PBMC from both donor populations
      secreted comparable amounts of IgE, if only the B cells were activated by soluble
      CD40L plus either exogenous IL-4 or IL-13. Further phenotypic analysis of T cells
      from atopics revealed that activated CD4+45RO- secreted IL-4 but no IL-13,
      whereas CD4+45RO+ memory T cells secreted low amounts of IL-4, but large amounts
      of IL-13. Accordingly, prolonged activation of native CD4+45RO- T cells in vitro
      induced expression of CD45RO, and strongly favored secretion of IL-13 rather than
      IL-4. Addition of exogenous IL-4 during activation further increased both IL-4
      and IL-13 production to a similar degree. However, the potential of CD4 T cells
      from atopics to deliver contact-dependent activation signals to B cells and to
      induce IgE production (in the absence of soluble CD40L) increased with prolonged
      activation, and coincided with IL-13 rather than IL-4 production. Under similar
      conditions, CD8 effector cells secreted IL-13 but no IL-4, did not express CD40L,
      and could not help Ig(E) production by B cells. These results suggest that, in
      atopy, persistently stimulated CD4+45RO+memory/effector T cells provide contact
      dependent activation signals to B cells, and that these cells may induce IgE
      switching largely via secretion of IL-13.

PMID- 8980465
TI  - Relationship between activated eosinophils of the bronchial mucosa and serum
      eosinophil cationic protein in atopic asthma.
AB  - We biopsied the bronchial mucosa of 20 atopic bronchial asthma patients and
      measured their serum eosinophil cationic protein (ECP) levels as a means of
      assessing whether serum ECP could be as a marker of airway eosinophil
      inflammation. We also investigated the relationship between serum ECP levels and
      airway hypersensitivity, pulmonary function, peak expiratory flow (PEF) and
      attack scores. EG2 monoclonal antibody was used to immunostain bronchial mucosal
      tissue, and positive cells were expressed as the number of positive cells per
      square millimeter of lamina propria mucosae. A significant correlation was found
      between bronchial mucosa EG2+ cell counts and serum ECP levels (r = 0.66, p <
      0.01), but no clear relationships were detected between serum ECP levels and
      airway hypersensitivity, pulmonary function, PEF or attack scores. Based on the
      above findings, serum ECP levels reflect airway eosinophilic inflammation, but
      ECP levels must be considered in combination with other parameters in relation to
      the pathophysiology of asthma.

PMID- 8980466
TI  - Differences in nonspecific bronchial responsiveness between patients with asthma
      and patients with rhinitis are not explained by type and degree of inhalant
      allergy.
AB  - Patients with allergic asthma have higher levels of nonspecific bronchial
      responsiveness than patients with allergic rhinitis. The aim of the study was to
      investigate whether this is caused by differences in the degree of allergy to
      inhalant allergens between asthmatics and rhinitics. Therefore, bronchial
      responsiveness to histamine was measured in 25 allergic patients with isolated
      upper airways symptoms. Nonspecific bronchial responsiveness in this group was
      compared with nonspecific bronchial responsiveness in a group of 136 patients
      with allergic asthma, with allergy and % predicted FEV1 as confounding variables.
      In addition, a matched pair analysis was performed. Twenty-five patients with
      nonallergic rhinitis served as controls to evaluate the influence of an IgE
      independent inflammatory reaction in the upper respiratory tract on the level of
      bronchial responsiveness. Furthermore, we investigated the level of nonspecific
      responsiveness in 18 healthy controls. In the patients with allergic asthma, a
      correlation was found between nonspecific bronchial responsiveness and IgE
      against indoor allergens (n = 136, r = 0.34, p < 0.001) and % predicted FEV1 (n =
      136, r = 0.37), p < 0.001). Patients with allergic asthma and patients with
      allergic rhinitis differed with respect to the level of bronchial responsiveness
      (p < 0.001), and the amount of specific IgE antibodies against indoor allergens
      (p = 0.01). The difference in level of bronchial responsiveness remained (p <
      0.001) after correction with % predicted FEV1 and specific IgE against indoor
      allergens as confounding variables. Similarly, after matching of patients with
      allergic rhinitis (n = 25) with patients with allergic asthma (n = 25) regarding
      the specific IgE, total IgE and age of the patients, the difference in level of
      bronchial responsiveness remained (p < 0.001). Patients with nonallergic rhinitis
      had higher levels of nonspecific bronchial responsiveness than healthy controls
      and did not differ from patients with allergic rhinitis. In conclusion, the
      results confirm that IgE against common indoor allergens plays an important role
      in the mechanism underlying nonspecific bronchial hyperresponsiveness. However,
      differences in bronchial responsiveness between patients with asthma and patients
      with rhinitis are not merely explained by differences in the IgE antibody
      concentrations.

PMID- 8980467
TI  - Dermatophagoides-farinae-induced pulmonary eosinophilic inflammation in mice.
AB  - Dermatophagoides farinae (Der f) is one of the most common species of dust mites
      that induce asthma and allergic rhinitis. We have reported that Der f challenge
      on sensitized mice elicited a distinct type of hypersensitivity, called early
      type hypersensitivity (ETH), in subcutaneous tissues and in airways. The airway
      ETH was accompanied by a series of inflammatory and immunological events
      including cytokine production, adhesion molecule expression, inflammatory cell
      infiltration, eosinophilia, and airway hyperreactivity. In the present study, we
      further defined the course of the Der-f-induced eosinophilia and examined the
      local cytokine gene expression and the roles of cytokines, mast-cell-derived
      vasoactive amines, and corticosteroids in the development of pulmonary
      eosinophilia. BALB/c mice were sensitized with crude extract of Der f in complete
      Freund's adjuvant and were intranasally challenged with Der f on day 14 after
      sensitization. The number of blood eosinophils, total and differential leukocyte
      counts in bronchoalveolar lavage (BAL) fluids, and the expression of cytokine
      genes in BAL cells were assessed at various time points after challenge for up to
      12 days. The total number of leukocytes in the BAL fluids was increased 6 h after
      challenge (AC) and peaked at 72 h. The early cellular response in the BAL fluids
      was dominated by neutrophils which were subsequently replaced by a marked
      infiltration of eosinophils. The number of eosinophils in BAL fluids increased at
      24 h and peaked at 72 h, making up 43% of all cells recovered by BAL. BAL
      eosinophils declined gradually to normal background levels around day 12.
      Concurrently, there was a significant reduction in the number of eosinophils in
      blood 24 h AC. The number of blood eosinophils increased thereafter, reached a
      peak at 72 h, and remained above baseline level for up to 10 days. Saline
      challenge did not induce eosinophilia in BAL fluids and blood of sensitized mice.
      Histopathological examination revealed a mixed granulocytic, monocytic pulmonary
      inflammation with a large number of eosinophils accumulating within the submucosa
      of the airways and blood vessels of sensitized mice after challenge. Der f
      challenge induced a sequential expression pattern of eight cytokine genes in BAL
      cells. The mRNA of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha
      strongly expressed throughout the course of the experiment. The IL-6 mRNA
      expression peaked at 0.5-72 h, IL-10 at 1-6 and 48-72 h, IL-4 at 6-72 h, IL-2 at
      6-96 h, IL-5 at 24-72 h, and interferon-gamma at 24-96 h. Intraperitoneal
      injection of sensitized mice with monoclonal antibody (mAb) to murine IL-5
      (TRFK5, 300 micrograms/mouse) 1 h before challenge caused 62% suppression of
      eosinophils in the BAL fluids. The concomitant accumulation of neutrophils and
      mononuclear cells, however, was not affected by this treatment. On the other
      hand, intranasal administration of mAb to murine TNF-alpha (MP6-XT3, 20
      micrograms/ mouse), but not IL-5, 1 h before challenge and 24 h AC significantly
      reduced the numbers of eosinophils, neutrophils, and lymphocytes in the BAL
      fluids. The intraperitoneal injection of dexamethasone (50 mg/kg) for a total of
      four times resulted in total inhibition of the Der-f-induced cellular responses,
      whereas vasoactive amine antagonists (diphenhydramine, ketanserin and
      cyprohepatidine) did not show any effect.

PMID- 8980468
TI  - Adenosine modulates endothelin-induced bronchoconstriction in guinea pig airway.
AB  - The present study was designed to determine whether endogenous and exogenous
      adenosine modulates endothelin (ET)-induced bronchoconstriction. Exogenous
      adenosine enhances ET-induced bronchoconstriction. Following pretreatment with
      adenosine deaminase and theophylline to eliminate or antagonize endogenous
      adenosine, ET-1-induced bronchoconstriction was significantly attenuated, but not
      that of ET-3. In conclusion, this is the first report of an enhancement of ET
      induced bronchoconstriction of guinea pig airways by endogenous and exogenous
      adenosine. Our findings may be useful in designing specific adenosine receptor
      antagonists as therapeutic agents in the management of bronchial asthma.

PMID- 8980469
TI  - Responses of monkeys with pollinosis to two major allergens of Japanese cedar
      pollen.
AB  - We examined the responses of two Japanese monkeys with pollinosis to two major
      allergens (Cry j 1 and Cry j 2) of Japanese cedar pollen. The two monkeys (A and
      B) had specific IgE antibodies to the allergens and showed a strong positive
      reaction to both of them in the intradermal test. In the histamine release test
      with peripheral blood mononuclear cells (PBMC), monkey A showed a typical pattern
      similar to that seen in human patients, while monkey B released a low level of
      histamine. The proliferative response of PBMC to both allergens in monkey A was
      weak, but was typical in monkey B. From clinical as well as immunological points
      of view, these monkeys may be a suitable animal model for Japanese cedar
      pollinosis in humans.

PMID- 8980470
TI  - Morphea after silicone gel breast implantation for cosmetic reasons in an HLA-B8,
      DR3-positive woman.
AB  - We describe an HLA-B8, DR3-positive patient with localized morphea after silicone
      gel breast implantation for cosmetic reasons. We believe that this case suggests
      that a genetic background, i.e. HLA-B8, DR3 haplotype, is involved in the
      autoimmune response to silicone.

PMID- 8980471
TI  - Transient CD80 expression defect in a patient with variable immunodeficiency and
      cyclic neutropenia.
AB  - CD80 expression on stimulated B cells of 9 common variable immunodeficiency
      (CVID) patients and 10 healthy control individuals was examined. Here we report
      on an exceptional CVID patient with recurrent episodes of cyclic neutropenia,
      skin vasculitis and recurrent infections associated with a transient, but
      reproducible CD80 expression defect on stimulated B cells. Concomitantly serum Ig
      levels were markedly reduced and B cell counts were low. Interestingly, after
      recovery from an episode of neutropenia and vasculitis we observed an improvement
      of the CD80 expression as well as an increase in the number of B cells and a
      recovery of IgM and IgG production in vivo and in vitro.

PMID- 8980473
TI  - Plant mRNA 3'-end formation.
AB  - Our understanding of how the 3' ends of mRNAs are formed in plants is rudimentary
      compared to what we know about this process in other eukaryotes. The salient
      features of plant pre-mRNAs that signal cleavage and polyadenylation remain
      obscure, and the biochemical mechanism is as yet wholly uncharacterized.
      Nevertheless, despite the lack of universally conserved cis-acting motifs, a
      common underlying architecture is emerging from functional analyses of plant
      poly(A) signals, allowing meaningful comparison with components of poly(A)
      signals in other eukaryotes. A plant poly(A) signal consists of one or more near
      upstream elements (NUE), each directing processing at a poly(A) site a short
      distance downstream of it, and an extensive far-upstream element (FUE) that
      enhances processing efficiency at all sites. By analogy with other systems, a
      model for a plant 3'-end processing complex can be proposed. Plant poly(A)
      polymerases have been isolated and partially characterised. These, together with
      hints that some processing factors are conserved in different organisms, opens
      promising avenues toward initial characterisation of the trans-acting factors
      involved in 3'-end formation of mRNAs in higher plants.

PMID- 8980475
TI  - RNA as a target and an initiator of post-transcriptional gene silencing in
      transgenic plants.
AB  - Post-transcriptional gene silencing in transgenic plants is the manifestation of
      a mechanism that suppresses RNA accumulation in a sequence-specific manner. The
      target RNA species may be the products of transgenes, endogenous plant genes or
      viral RNAs. For an RNA to be a target it is necessary only that it has sequence
      homology to the sense RNA product of the transgene. There are three current
      hypotheses to account for the mechanism of post transcriptional gene silencing.
      These models all require production of an antisense RNA of the RNA targets to
      account for the specificity of the mechanism. There could be either direct
      transcription of the antisense RNA from the transgene, antisense RNA produced in
      response to over expression of the transgene or antisense RNA produced in
      response to the production of an aberrant sense RNA product of the transgene. To
      determine which of these models is correct it will be necessary to find out
      whether transgene methylation, which is frequently associated with the potential
      of transgenes to confer post-transcriptional gene silencing, is a cause or a
      consequence of the process.

PMID- 8980474
TI  - Control of mRNA stability in higher plants.
AB  - The degradation rates of different mRNAs in higher plants can vary over a broad
      range and are regulated by a variety of endogenous and exogenous stimuli. During
      the past several years, efforts to better understand the control of mRNA
      stability in plants have increased considerably and this has led to improved
      methodologies and important mechanistic insights. In this review, we highlight
      some of the most interesting examples of plant transcripts that are controlled at
      the level of mRNA decay and discuss what has been learned from their study.
      Experiments that implicate or demonstrate the involvement of particular cis- and
      trans-acting factors in mRNA decay pathways are a major focus, as are those
      experiments that have led to mechanistic models. Emphasis is also placed on
      studies that address the relationship between translation and mRNA stability. Our
      current knowledge indicates that some of the determinants and pathways for mRNA
      decay may differ in plants compared to other eukaryotes, whereas others appear to
      be similar. This knowledge, coupled with the availability of biochemical,
      molecular and genetic approaches to elucidate plant mRNA decay mechanisms, should
      continue to lead to findings of novel and general significance.

PMID- 8980472
TI  - Splicing of precursors to mRNA in higher plants: mechanism, regulation and sub
      nuclear organisation of the spliceosomal machinery.
AB  - The removal of introns from pre-mRNA transcripts and the concomitant ligation of
      exons is known as pre-mRNA splicing. It is a fundamental aspect of constitutive
      eukaryotic gene expression and an important level at which gene expression is
      regulated. The process is governed by multiple cis-acting elements of limited
      sequence content and particular spatial constraints, and is executed by a dynamic
      ribonucleoprotein complex termed the spliceosome. The mechanism and regulation of
      pre-mRNA splicing, and the sub-nuclear organisation of the spliceosomal machinery
      in higher plants is reviewed here. Heterologous introns are often not processed
      in higher plants indicating that, although highly conserved, the process of pre
      mRNA splicing in plants exhibits significant differences that distinguish it from
      splicing in yeast and mammals. A fundamental distinguishing feature is the
      presence of and requirement for AU or U-rich intron sequence in higher-plant pre
      mRNA splicing. In this review we document the properties of higher-plant introns
      and trans-acting spliceosomal components and discuss the means by which these
      elements combine to determine the accuracy and efficiency of pre-mRNA processing.
      We also detail examples of how introns can effect regulated gene expression by
      affecting the nature and abundance of mRNA in plants and list the effects of
      environmental stresses on splicing. Spliceosomal components exhibit a distinct
      pattern of organisation in higher-plant nuclei. Effective probes that reveal this
      pattern have only recently become available, but the domains in which
      spliceosomal components concentrate were identified in plant nuclei as enigmatic
      structures some sixty years ago. The organisation of spliceosomal components in
      plant nuclei is reviewed and these recent observations are unified with previous
      cytochemical and ultrastructural studies of plant ribonuleoprotein domains.

PMID- 8980476
TI  - RNA structure and the regulation of gene expression.
AB  - RNA secondary and tertiary structure is involved in post-transcriptional
      regulation of gene expression either by exposing specific sequences or through
      the formation of specific structural motifs. An overview of RNA secondary and
      tertiary structures known from biophysical studies is followed by a review of
      examples of the elements of RNA processing, mRNA stability and translation of the
      messenger. These structural elements comprise sense-antisense double-stranded
      RNA, hairpin and stem-loop structures, and more complex structures such as
      bifurcations, pseudoknots and triple-helical elements. Metastable structures
      formed during RNA folding pathway are also discussed. The examples presented are
      mostly chosen from plant systems, plant viruses, and viroids. Examples from
      bacteria or fungi are discussed only when unique regulatory properties of RNA
      structures have been elucidated in these systems.

PMID- 8980478
TI  - Translational control of cellular and viral mRNAs.
AB  - We are becoming increasingly aware of the role that translational control plays
      in regulating gene expression in plants. There are now many examples in which
      specific mechanisms have evolved at the translational level that directly impact
      the amount of protein produced from an mRNA. All regions of an mRNA, i.e., the 5'
      leader, the coding region, and the 3'-untranslated region, have the potential to
      influence translation. The 5'-terminal cap structure and the poly(A) tail at the
      3' terminus serve as additional elements controlling translation. Many viral
      mRNAs have evolved alternatives to the cap and poly(A) tail that are functionally
      equivalent. Nevertheless, for both cellular and viral mRNAs, a co-dependent
      interaction between the terminal controlling elements appears to be the universal
      basis for efficient translation.

PMID- 8980477
TI  - The plant translational apparatus.
AB  - Protein synthesis in both eukaryotic and prokaryotic cells is a complex process
      requiring a large number of macromolecules: initiation factors, elongation
      factors, termination factors, ribosomes, mRNA, amino-acylsynthetases and tRNAs.
      This review focuses on our current knowledge of protein synthesis in higher
      plants.

PMID- 8980479
TI  - Translation in plants--rules and exceptions.
AB  - Translation processes in plants are very similar to those in other eukaryotic
      organisms and can in general be explained with the scanning model. Particularly
      among plant viruses, unconventional mRNAs are frequent, which use modulated
      translation processes for their expression: leaky scanning, translational stop
      codon readthrough or frameshifting, and transactivation by virus-encoded proteins
      are used to translate polycistronic mRNAs; leader and trailer sequences confer
      (cap-independent) efficient ribosome binding, usually in an end-dependent
      mechanism, but true internal ribosome entry may occur as well; in a ribosome
      shunt, sequences within an RNA can be bypassed by scanning ribosomes. Translation
      in plant cells is regulated under conditions of stress and during development,
      but the underlying molecular mechanisms have not yet been determined. Only a
      small number of plant mRNAs, whose structure suggests that they might require
      some unusual translation mechanisms, have been described.

PMID- 8980482
TI  - Plasmodesmal cell-to-cell transport of proteins and nucleic acids.
AB  - The complexity associated with post-translational processing, in terms of protein
      sorting and delivery is now well understood. Although such studies have been
      focused almost exclusively on the fate of proteins within the cell in which they
      are synthesized, recent studies indicate that it is time to broaden this focus to
      incorporate the concept of intercellular targeting of proteins. Direct evidence
      is now available that viral and endogenous proteins can be synthesized in a
      particular cell and subsequently transported into neighboring (or more distant)
      cells. Plasmodesmata, plasma membrane-lined cytoplasmic pores, are thought to
      establish the intercellular pathway responsible for this cell-to-cell trafficking
      of macromolecules (proteins and nucleic acids). These recent findings establish a
      new paradigm for understanding the manner in which higher plants exert control
      over developmental processes. We discuss the concept that programming of plant
      development involves supracellular control achieved by plasmodesmal trafficking
      of informational molecules, herein defined as supracellular control proteins
      (SCPs). This novel concept may explain why, in plants, cell fate is determined by
      position rather than cell lineage. Finally, the circulation of long-distance
      SCPs, within the phloem, may provide the mechanism by which the plant signals to
      the shoot apical meristem that it is time to switch to the reproductive phase of
      its development.

PMID- 8980480
TI  - Molecular chaperones and protein folding in plants.
AB  - Protein folding in vivo is mediated by an array of proteins that act either as
      'foldases' or 'molecular chaperones'. Foldases include protein disulfide
      isomerase and peptidyl prolyl isomerase, which catalyze the rearrangement of
      disulfide bonds or isomerization of peptide bonds around Pro residues,
      respectively. Molecular chaperones are a diverse group of proteins, but they
      share the property that they bind substrate proteins that are in unstable, non
      native structural states. The best understood chaperone systems are HSP70/DnaK
      and HSP60/GroE, but considerable data support a chaperone role for other
      proteins, including HSP100, HSP90, small HSPs and calnexin. Recent research
      indicates that many, if not all, cellular proteins interact with chaperones
      and/or foldases during their lifetime in the cell. Different chaperone and
      foldase systems are required for synthesis, targeting, maturation and degradation
      of proteins in all cellular compartments. Thus, these diverse proteins affect an
      exceptionally broad array of cellular processes required for both normal cell
      function and survival of stress conditions. This review summarizes our current
      understanding of how these proteins function in plants, with a major focus on
      those systems where the most detailed mechanistic data are available, or where
      features of the chaperone/foldase system or substrate proteins are unique to
      plants.

PMID- 8980483
TI  - Proteolysis in plants: mechanisms and functions.
AB  - Proteolysis is essential for many aspects of plant physiology and development. It
      is responsible for cellular housekeeping and the stress response by removing
      abnormal/misfolded proteins, for supplying amino acids needed to make new
      proteins, for assisting in the maturation of zymogens and peptide hormones by
      limited cleavages, for controlling metabolism, homeosis, and development by
      reducing the abundance of key enzymes and regulatory proteins, and for the
      programmed cell death of specific plant organs or cells. It also has potential
      biotechnological ramifications in attempts to improve crop plants by modifying
      protein levels. Accumulating evidence indicates that protein degradation in
      plants is a complex process involving a multitude of proteolytic pathways with
      each cellular compartment likely to have one or more. Many of these have
      homologous pathways in bacteria and animals. Examples include the chloroplast
      ClpAP protease, vacuolar cathepsins, the KEX2-like proteases of the secretory
      system, and the ubiquitin/26S proteasome system in the nucleus and cytoplasm. The
      ubiquitin-dependent pathway requires that proteins targeted for degradation
      become conjugated with chains of multiple ubiquitins; these chains then serve as
      recognition signals for selective degradation by the 26S proteasome, a 1.5 MDa
      multisubunit protease complex. The ubiquitin pathway is particularly important
      for developmental regulation by selectively removing various cell-cycle
      effectors, transcription factors, and cell receptors such as phytochrome A. From
      insights into this and other proteolytic pathways, the use of
      phosphorylation/dephosphorylation and/or the addition of amino acid tags to
      selectively mark proteins for degradation have become recurring themes.

PMID- 8980484
TI  - Regulation of gene expression in plant mitochondria.
AB  - Many genes is plant mitochondria have been analyzed in the past 15 years and
      regulatory processes controlling gene expression can now be investigated. In
      vitro systems capable of initiating transcription faithfully at promoter sites
      have been developed for both monocot and dicot plants and will allow the
      identification of the interacting nucleic acid elements and proteins which
      specify and guide transcriptional activities. Mitochondrial activity, although
      required in all plant tissues, is capable of adapting to specific requirements by
      regulated gene expression. Investigation of the factors governing the quality and
      quantity of distinct RNAs will define the extent of interorganelle regulatory
      interference in mitochondrial gene expression.

PMID- 8980481
TI  - Transport of proteins in eukaryotic cells: more questions ahead.
AB  - Some newly synthesized proteins contain signals that direct their transport to
      their final location within or outside of the cell. Targeting signals are
      recognized by specific protein receptors located either in the cytoplasm or in
      the membrane of the target organelle. Specific membrane protein complexes are
      involved in insertion and translocation of polypeptides across the membranes.
      Often, additional targeting signals are required for a polypeptide to be further
      transported to its site of function. In this review, we will describe the
      trafficking of proteins to various cellular organelles (nucleus, chloroplasts,
      mitochondria, peroxisomes) with emphasis on transport to and through the
      secretory pathway.

PMID- 8980485
TI  - Regulation of gene expression in chloroplasts of higher plants.
AB  - Chloroplasts contain their own genetic system which has a number of prokaryotic
      as well as some eukaryotic features. Most chloroplast genes of higher plants are
      organized in clusters and are cotranscribed as polycistronic pre-RNAs which are
      generally processes into many shorter overlapping RNA species, each of which
      accumulates of steady-state RNA levels. This indicates that posttranscriptional
      RNA processing of primary transcripts is an important step in the control of
      chloroplast gene expression. Chloroplast RNA processing steps include RNA
      cleavage/trimming, RNA splicing, ENA editing and RNA stabilization. Several
      chloroplast genes are interrupted by introns and therefore require processing for
      gene function. In tobacco chloroplasts, 18 genes contain introns, six for tRNA
      genes and 12 for protein-encoding genes. A number of specific proteins and RNA
      factors are believed to be involved in splicing and maturation of pre-RNAs in
      chloroplasts. Processing enzymes and RNA-binding proteins which could be involved
      in posttranscriptional steps have been identified in the last several years. Our
      current knowledge of the regulation of gene expression in chloroplasts of higher
      plants is overviewed and further studies on this matter are also considered.

PMID- 8980486
TI  - Post-transcriptional regulation of chloroplast gene expression in Chlamydomonas
      reinhardtii.
AB  - The biosynthesis of the photosynthetic apparatus depends on the concerted action
      of the nuclear and chloroplast genetic systems. Numerous nuclear and chloroplast
      mutants of Chlamydomonas deficient in photosynthetic activity have been isolated
      and characterized. While several of these mutations alter the genes of components
      of the photosynthetic complexes, a large number of the mutations affect the
      expression of chloroplast genes involved in photosynthesis. Most of these
      mutations are nuclear and only affect the expression of a single chloroplast
      gene. The mutations examined appear to act principally at post-transcriptional
      steps such as RNA stability, RNA processing, cis- and trans-splicing and
      translation. Directed chloroplast DNA surgery through biolistic transformation
      has provided a powerful tool for identifying important cis elements involved in
      chloroplast gene expression. Insertion of chimeric genes consisting of
      chloroplast regulatory regions fused to reporter genes into the chloroplast
      genome has led to the identification of target sites of the nuclear-encoded
      functions affected in some of the mutants. Biochemical studies have identified a
      set of RNA-binding proteins that interact with the 5'-untranslated regions of
      plastid mRNAs. The binding activity of some of these factors appears to be
      modulated by light and by the growth conditions.

PMID- 8980487
TI  - RNA editing in plant mitochondria and chloroplasts.
AB  - In the mitochondria and chloroplasts of higher plants there is an RNA editing
      activity responsible for specific C-to-U conversions and for a few U-to-C
      conversions leading to RNA sequences different from the corresponding DNA
      sequences. RNA editing is a post-transcriptional process which essentially
      affects the transcripts of protein coding genes, but has also been found to
      modify non-coding transcribed regions, structural RNAs and intron sequences. RNA
      editing is essential for correct gene expression: proteins translated from edited
      transcripts are different from the ones deduced from the genes sequences and
      usually present higher similarity to the corresponding non-plant homologues.
      Initiation and stop codons can also be created by RNA editing. RNA editing has
      also been shown to be required for the stabilization of the secondary structure
      of introns and tRNAs. The biochemistry of RNA editing in plant organelles is
      still largely unknown. In mitochondria, recent experiments indicate that RNA
      editing may be a deamination process. A plastid transformation technique showed
      to be a powerful tool for the study of RNA editing. The biochemistry as well as
      the evolutionary features of RNA editing in both organelles are compared in order
      to identify common as well as organelle-specific components.

PMID- 8980489
TI  - Optimizing expression of transgenes with an emphasis on post-transcriptional
      events.
AB  - Introducing a foreign gene into a new plant host does not always result in a high
      level of expression of the incoming gene. Numerous promoters have been used to
      express foreign genes in different plant tissues, but there are sometime various
      features of the new gene which are deleterious to expression in the new host.
      There are a number of post-transcriptional steps in the expression of a gene and
      sometimes sequences present in a particular coding region can resemble the
      signals which initiate these processing steps. When aberrantly carried out, these
      steps diminish the level of expression. By removing such fortuitous signals, one
      can dramatically increase expression of a transgene in plants. Ensuring proper
      protein folding and/or targeting the protein product to a particular cellular
      compartment can also be used to increase the level of protein obtained. The
      various methods used to optimize expression of a foreign gene in plants by
      concentrating on post-transcriptional events are discussed.

PMID- 8980491
TI  - Plant nuclear tRNA(Met) genes are ubiquitously interrupted by introns.
AB  - We have isolated three independent clones for nuclear elongator tRNA(Met) genes
      from an Arabidopsis DNA library using a tRNA(Met)-specific probe generated by
      PCR. Each of the coding sequences for tRNAMet in these clones is identical and is
      interrupted by an identical 11 bp long intervening sequence at the same position
      in the anticodon loop of the tRNA. Their sequences differ at two positions from
      the intron in a soybean counterpart. Southern analysis of Arabidopsis DNA
      demonstrates that a gene family coding for tRNA(Met) is dispersed at at least
      eight loci in the genome. The unspliced precursor tRNA(Met) intermediate was
      detected by RNA analysis using an oligonucleotide probe complementary to the
      putative intron sequence. In order to know whether introns commonly interrupt
      plant tRNA(Met) genes, their coding sequences were PCR-amplified from the DNAs of
      eight phylogenetically separate plant species. All 53 sequences determined
      contain 10 to 13 bp long intervening sequences, always positioned one base
      downstream from the anticodon. They can all be potentially folded into the
      secondary structure characteristic for plant intron-containing precursor tRNAs.
      Surprisingly, GC residues are always present at the 5'-distal end of each intron.

PMID- 8980490
TI  - Coordinated activation of as-1-type elements and a tobacco glutathione S
      transferase gene by auxins, salicylic acid, methyl-jasmonate and hydrogen
      peroxide.
AB  - The molecular mechanism of signal transduction pathways which mediate the action
      of phytohormones are poorly understood. Recently, we and others have shown that
      the as -1 type cis-acting elements can respond to auxin and salicylic acid, two
      well-characterized signaling molecules in plants. In the present work, we have
      examined a comprehensive set of physiological and abiotic agents and found that
      auxin, salicylic acid and methyl-jasmonate are three effective inducers of the as
      1-type elements in transgenic tobacco. Using a cell suspension culture containing
      a synthetic promoter-GUS fusion, we demonstrated rapid and sensitive induction of
      the as-1-type element by these phytohormones. Furthermore, a tobacco glutathione
      S-transferase gene, GNT35, that contains an as-1-type binding site in its
      promoter is also inducible by auxin, salicylic acid and methyl-jasmonate with
      similar kinetics. As Ulmasov et al. have recently reported, we found that the as
      1-type elements can also respond to weak/inactive analogues of auxin and
      salicylic acid. In addition, we show that hydrogen peroxide can also effectively
      activate the expression of GNT35 as well as the as-1-type element in a cell
      suspension culture, but not with whole seedlings. These results are discussed
      with respect to the possible mechanism(s) through which a single cis element may
      respond to a diverse array of molecules.

PMID- 8980488
TI  - Gene expression from viral RNA genomes.
AB  - This review is centered on the major strategies used by plant RNA viruses to
      produce the proteins required for virus multiplication. The strategies at the
      level of transcription presented here are synthesis of mRNA or subgenomic RNAs
      from viral RNA templates, and 'cap-snatching'. At the level of translation,
      several strategies have been evolved by viruses at the steps of initiation,
      elongation and termination. At the initiation step, the classical scanning mode
      is the most frequent strategy employed by viruses; however in a vast number of
      cases, leaky scanning of the initiation complex allows expression of more than
      one protein from the same RNA sequence. During elongation, frameshift allows the
      formation of two proteins differing in their carboxy terminus. At the termination
      step, suppression of termination produces a protein with an elongated carboxy
      terminus. The last strategy that will be described is co- and/or post
      translational cleavage of a polyprotein precursor by virally encoded proteinases.
      Most (+)-stranded RNA viruses utilize a combination of various strategies.

PMID- 8980492
TI  - A pollen allergen-encoding gene is expressed in wheat ovaries.
AB  - To isolate genes specifically expressed at the initiation of plant embryo
      development we have applied a sensitive subtractive hybridization technique for
      three isogenic wheat lines of the so-called 'Salmon system' with either zygotic
      or autonomous embryo development. Here we present a gene sequence showing a high
      homology to grass pollen allergens of type II/III thought to be expressed in
      pollen tissue only. Surprisingly, the pollen allergen-like sequence, designated
      Tri a III, is also expressed in gynoecia of the sexual, male fertile wheat line
      '(aestivum)-Salmon', whereas the two parthenogenetic and male sterile wheat lines
      '(caudata)-Salmon' and '(kotschyi)-Salmon' completely lack any Tri a III
      transcript. Our data suggest a positive correlation between the expression of
      this clone and the manifestation of male fertility. Northern and in situ
      hybridization analysis revealed that, in addition to its presence in pollen, Tri
      a III is expressed in the parenchymatous tissue of '(aestivum)-Salmon' ovaries
      exclusively at the day of anthesis. This precise temporal and spatial expression
      pattern suggests a more general function of the pollen allergen-like sequence Tri
      a III not limited to the exhibition of allergens in pollen grains.

PMID- 8980493
TI  - Cloning and expression of transaldolase from potato.
AB  - We have isolated a cDNA encoding transaldolase, an enzyme of the pentose
      phosphate pathway, from potato (Solanum tuberosum). The 1.5 kb cDNA encodes a
      protein of 438 amino acid residues with a molecular mass of 47.8 kDa. When the
      potato cDNA was expressed in Escherichia coli a 45 kDa protein with transaldolase
      activity was produced. The first 62 amino acids of the deduced amino acid
      sequence represent an apparent plastid transit sequence. While the potato
      transaldolase has considerable similarity to the enzyme from cyanobacteria and
      Mycobacterium leprae, similarity to the conserved transaldolase enzymes from
      humans, E. coli and Saccharomyces cerevisiae is more limited. Northern analysis
      indicated that the transaldolase mRNA accumulated in tubers in response to
      wounding. Probing the RNA from various potato tissues indicated that the
      transaldolase mRNA accumulation to higher levels in the stem of mature potato
      plants than in either leaves or tubers. These data are consistent with a role for
      this enzyme in lignin biosynthesis.

PMID- 8980494
TI  - Structure of the dehydrin tas14 gene of tomato and its developmental and
      environmental regulation in transgenic tobacco.
AB  - We have isolated a genomic clone encoding tomato TAS14, a dehydrin that
      accumulates in response to mannitol, NaCl or abscisic acid (ABA) treatment. A
      fragment of tas14 gene containing the region from -2591 to +162 fused to beta
      glucuronidase gene drives ABA- and osmotic stress-induced GUS expression in
      transgenic tobacco. Histochemical analysis of salt-, mannitol- and ABA-treated
      plants showed GUS activity mainly localized to vascular tissues, outer cortex and
      adventitious root meristems, coinciding with the previously observed distribution
      of TAS14 protein in salt-stressed tomato plants. In addition, GUS activity was
      also observed in guard cells, trichomes and leaf axils. Developmentally regulated
      gus expression was studied in unstressed plants and found to occur not only in
      embryos, but also in flowers and pollen. Tas14 expression in floral organs was
      confirmed by northern blots of tomato flowers.

PMID- 8980495
TI  - The Chlamydomonas reinhardtii LI818 gene represents a distant relative of the
      cabI/II genes that is regulated during the cell cycle and in response to
      illumination.
AB  - In the green unicellular alga Chlamydomonas reinhardtii, as in higher plants, the
      expression of the genes encoding the chlorophyll a/b-binding (CAB) polypeptides
      associated with photosystem I (PSI) and photosystem II (PSII) is regulated by
      endogenous (circadian clock) and exogenous signals (light and temperature). The
      circadian clock ensures that the oscillation in the levels of the different cab
      mRNAs is continuously kept in phase with light/dark (LD) cycles and is maximal by
      the middle of the day. On the other hand, light controls the amplitude of the
      oscillations. We report here the cloning and characterization of the C.
      reinhardtii LI818 gene, which identifies a CAB-related polypeptide and whose
      expression is regulated quite differently from the cab I/II genes. We show: (1)
      that in LD synchronized Chlamydomonas cells LI818 mRNA accumulation is subject to
      dual regulation that involves separable regulation by light and an endogenous
      oscillator; (2) that LI818 mRNA is fully expressed several hours before the cab
      I/II mRNAs and that the latter accumulate concomitantly; (3) that blocking the
      electron flow through PSII using DCMU prevents cells from accumulating cab I/II
      mRNAs but not LI818 mRNA and (4) that the accumulation of LI818 mRNA is abolished
      by blocking cytoplasmic protein synthesis, suggesting that these regulatory
      mechanisms are mediated by labile proteins.

PMID- 8980496
TI  - Molecular characterization of transketolase (EC 2.2.1.1) active in the Calvin
      cycle of spinach chloroplasts.
AB  - A cDNA encoding the Calvin cycle enzyme transketolase (TKL; EC 2.2.1.1) was
      isolated from Sorghum bicolor via subtractive differential hybridization, and
      used to isolate several full-length cDNA clones for this enzyme from spinach.
      Functional identity of the encoded mature subunit was shown by an 8.6-fold
      increase of TKL activity upon induction of Escherichia coli cells that
      overexpress the spinach TKL subunit under the control of the bacteriophage T7
      promoter. Chloroplast localization of the cloned enzyme is shown by processing of
      the in vitro synthesized precursor upon uptake by isolated chloroplasts. Southern
      blot-analysis suggests that TKL is encoded by a single gene in the spinach
      genome. TKL proteins of both higher-plant chloroplasts and the cytosol of non
      photosynthetic eukaryotes are found to be unexpectedly similar to eubacterial
      homologues, suggesting a possible eubacterial origin of these nuclear genes.
      Chloroplast TKL is the last of the demonstrably chloroplast-localized Calvin
      cycle enzymes to have been cloned and thus completes the isolation of gene probes
      for all enzymes of the pathway in higher plants.

PMID- 8980497
TI  - Higher-plant chloroplast and cytosolic fructose-1,6-bisphosphatase isoenzymes:
      origins via duplication rather than prokaryote-eukaryote divergence.
AB  - Full-size cDNAs encoding the precursors of chloroplast fructose-1,6
      bisphosphatase (FBP), sedoheptulose-1,7-bisphosphatase (SBP), and the small
      subunit of Rubisco (RbcS) from spinach were cloned. These cDNAs complete the set
      of homologous probes for all nuclear-encoded enzymes of the Calvin cycle from
      spinach (Spinacia oleracea L.). FBP enzymes not only of higher plants but also of
      non-photosynthetic eukaryotes are found to be unexpectedly similar to eubacterial
      homologues, suggesting a eubacterial origin of these eukaryotic nuclear genes.
      Chloroplast and cytosolic FBP isoenzymes of higher plants arose through a gene
      duplication event which occurred early in eukaryotic evolution. Both FBP and SBP
      of higher plant chloroplasts have acquired substrate specificity, i.e. have
      undergone functional specialization since their divergence from bifunctional
      FBP/SBP enzymes of free-living eubacteria.

PMID- 8980498
TI  - A novel plant peptidyl-prolyl-cis-trans-isomerase (PPIase): cDNA cloning,
      structural analysis, enzymatic activity and expression.
AB  - A novel cDNA encoding for a peptidyl-prolyl-cis-trans-isomerase (PPIase)
      belonging to the FK506-binding protein (FKBP) family was isolated from wheat. It
      contains an open reading frame of 559 amino acids and it represents the first
      plant FKBP-PPIase to be cloned. It possesses a unique sequence which is composed
      of three FKPB-like domains, in addition to a putative tetratricopeptide repeat
      (TPR) motif and a calmodulin-binding site. The recombinant FKBP-PPIase expressed
      in and purified from Escherichia coli exhibits PPIase activity that is
      efficiently inhibited by the immunosuppressive drugs FK506 and rapamycin.
      Northern blot analysis showed that wheat FKBP was found mainly in young tissues.
      Polyclonal antibodies revealed the presence of cross-reacting proteins in
      embryos, roots and shoots. The unique structural features, the enzymatic activity
      and the presence of putative isoforms in wheat tissues indicate the possibility
      of the involvement of wheat PPIase in essential biological functions, similar to
      other members of the FKBP gene family.

PMID- 8980499
TI  - Functional studies of chloroplast glyceraldehyde-3-phosphate dehydrogenase
      subunits A and B expressed in Escherichia coli: formation of highly active A4 and
      B4 homotetramers and evidence that aggregation of the B4 complex is mediated by
      the B subunit carboxy terminus.
AB  - Chloroplast glyceraldehyde-3-phosphate dehydrogenase (phosphorylating, E.C.
      1.2.1.13) (GAPDH) of higher plants exists as an A2B2 heterotetramer that
      catalyses the reductive step of the Calvin cycle. In dark chloroplasts the enzyme
      exhibits a molecular mass of 600 kDa, whereas in illuminated chloroplasts the
      molecular mass is altered in favor of the more active 150 kDa form. We have
      expressed in Escherichia coli proteins corresponding to the mature A and B
      subunits of spinach chloroplast GAPDH (GapA and GapB, respectively) in addition
      to a derivative of the B subunit lacking the GapB-specific C-terminal extension
      (CTE). One mg of each of the three proteins so expressed was purified to
      electrophoretic homogeneity with conventional methods. Spinach GapA purified from
      E. coli is shown to be a highly active homotetramer (50-70 U/mg) which does not
      associate under aggregating conditions in vitro to high-molecular-mass (HMM)
      forms of ca. 600 kDa. Since B4 forms of the enzyme have not been described from
      any source, we were surprised to find that spinach GapB purified from E. coli was
      active (15-35 U/mg). Spinach GapB lacking the CTE purified from E. coli is more
      highly active (130 U/mg) than GapB with the CTE. Under aggregating conditions,
      GapB lacking the CTE is a tetramer that does not associate to HMM forms whereas
      GapB with the CTE occurs exclusively as an aggregated HMM form. The data indicate
      that intertetramer association of chloroplast GAPDH in vitro occurs through GapB
      mediated protein-protein interaction.

PMID- 8980500
TI  - The 22 bp W1 element in the pea lectin promoter is necessary and, as a multimer,
      sufficient for high gene expression in tobacco seeds.
AB  - The pea lectin (Psl) gene encodes an abundant seed protein. Its seed-specific
      expression pattern is conserved in transgenic tobacco plants. Progressive 5'
      promoter deletions resulted in a gradual decrease of transcriptional activity in
      tobacco seed. A fragment of 115 bp still conferred seed-specific expression
      albeit at a low level. This fragment contains a 22 bp element (W1), which has
      been demonstrated to be important for seed-specific expression when coupled as a
      trimer to a heterologous TATA box (de Pater et al., Plant Cell 5:877-886, 1993).
      Here we show that deletion of W1 in the natural promoter context resulted in a
      strongly decreased level of gene expression. A 4 bp mutation of W1 reduced the
      expression of truncated derivatives of the Psl promoter. A single copy of W1
      coupled to the TATA box of the CaMV 35S promoter directed low gene expression in
      seeds and leaves. Multimerization enhanced the expression in seeds up to 100
      fold, to levels found with the Psl promoter, whereas the expression level in
      leaves remained low. These results demonstrate that the W1 element is an
      essential control element in the Psl promoter. When taken out of its natural
      context and multimerized, it is sufficient for high expression in seeds.

PMID- 8980502
TI  - Arabidopsis consensus intron sequences.
AB  - We have analysed 998 Arabidopsis intron sequences in the EMBL database. All
      Arabidopsis introns to adhere to the :GU ... AG: rule with the exception of 1% of
      introns with :GC at their 5' ends. Virtually all of the introns contained a
      putative branchpoint sequence (YUNAN) 18 to 60 nt upstream of the 3' splice site.
      Although a polypyrimidine tract was much less apparent than in vertebrate
      introns, the most common nucleotide in the region upstream of the 3' splice site
      was uridine. Consensus sequences for 5' and 3' splice sites and branchpoint
      sequences for Arabidopsis introns are presented.

PMID- 8980501
TI  - RNA expression patterns of a type 2 metallothionein-like gene from rice.
AB  - A type 2 metallothionein-like gene from rice, OsMT-2 (Oryza sativa
      metallothionein-like gene-2), was isolated in its cDNA form and sequenced. By
      northern analyses OsMT-2 expression was shown to be induced under stress by
      sucrose starvation, heat shock and, to a lesser extent, abscisic acid, but not
      excess metals, including copper. Its response to sucrose starvation was transient
      and different from OsMT-1, a type 1 metallothionein-like gene of rice inducible
      by copper. These results suggest that while OsMT-2 is also involved in cellular
      response to stress, its function may be complementary to that of OsMT-1.

PMID- 8980503
TI  - Site-directed mutagenesis of the CP 47 protein of photosystem II: 167W in the
      lumenally exposed loop C is required for photosystem II assembly and stability.
AB  - The intrinsic chlorophyll-protein CP 47 is a component of photosystem II which
      functions in both light-harvesting and oxygen evolution. Using site-directed
      mutagenesis we have produced the mutant W167S which lies in loop C of CP 47. This
      strain exhibited a 75% loss in oxygen evolution activity and grew extremely
      slowly in the absence of glucose. Examination of normalized oxygen evolution
      traces indicated that the mutant was susceptible to photoinactivation. Analysis
      of the variable fluorescence yield indicated that the mutant accumulated very few
      functional PS II reaction centers. This was confirmed by immunoblotting
      experiments. Interestingly, when W167S was grown in the presence of 20 microM
      DCMU, the mutant continued to exhibit these defects. These results indicate that
      tryptophan 167 in loop C of CP 47 is important for the assembly and stability of
      the PS II reaction center.

PMID- 8980504
TI  - Salt stress induces an increased expression of V-type H(+)-ATPase in mature sugar
      beet leaves.
AB  - In the halotolerant sugar beet co-expression of V-ATPase and a vacuolar Na+/H(+)
      antiporter provides a mechanism for vacuolar salt sequestration. To analyze salt
      induced changes in the expression of the vacuolar H(+)-ATPase (V-ATPase) a
      partial cDNA of the proton-channel forming subunit c was cloned by RT-PCR.
      Southern blot analysis indicated a small gene family. In control plants
      transcript levels were high in roots and young growing leaves but low in fully
      expanded leaves. In mature leaves salt exposure (400 mM, 48 h) induced a strong
      increase in subunit c-mRNA. Transcripts for the catalytic subunit A followed a
      similar developmental and stress-modulated pattern, indicating a coordinate
      regulation of transcripts for both V-ATPase subunits. Concomittant with the mRNA
      increases the amount of V-ATPase protein increased as well.

PMID- 8980506
TI  - Analysis of the occurrence and nature of repeated DNA in an 850 kb region of
      Arabidopsis thaliana chromosome 4.
AB  - The occurrence and nature of repeated DNA sequences has been analysed within an
      850 kb YAC contig on Arabidopsis thaliana chromosome 4. Hybridization analysis
      with seven RFLP markers, six cosmid contigs, 29 YAC end probes and eight YAC
      clones showed that a least 585 kb of the 850 kb contained only low-copy
      sequences. One YAC end probe, EG15C8LE, hybridized to multiple genomic fragments
      and contained a sequence with predicted protein homology to cytochrome P450
      monooxygenases. Another one, EG11B7RE, was found to be non-contiguous with the
      other YAC clones and contained a dispersed repetitive sequence associated with
      centromeric regions.

PMID- 8980505
TI  - Nucleotide sequences of nuclear tRNA(Cys) genes from Nicotiana and Arabidopsis
      and expression in HeLa cell extract.
AB  - We have recently characterized Nicotiana cytoplasmic (cyt) tRNA(GCA)Cys as a
      novel UGA suppressor tRNA. Here we have isolated its corresponding (NtC1) and a
      variant (NtC2) gene from a genomic library of Nicotiana rustica. Both tRNA(Cys)
      genes are efficiently transcribed in HeLa cell nuclear extract and yield mature
      cyt tRNAs(Cys). Sequence analysis of the upstream region of the RAD51 single-copy
      gene of the Arabidopsis thaliana genome revealed a cluster of three tRNA(Cys)
      genes which have the same polarity and comprise highly similar flanking
      sequences. Of the three Arabidopsis tRNA(Cys) genes only one (i.e. AtC2) appears
      to code for a functional gene which exhibits an almost identical nucleotide
      sequence to NtC1. These are the first sequenced nuclear tDNAs(Cys) of plant
      origin.

PMID- 8980508
TI  - Expression of anthocyanin biosynthesis pathway genes in red and white grapes.
AB  - The expression of seven genes from the anthocyanin biosynthesis pathway was
      determined in different tissues of Shiraz grapevines. All of the tissues
      contained proanthocyanidins, but only the berry skin accumulated anthocyanins. In
      most tissues, all of the flavonoid genes except UDP glucose-flavonoid 3-o
      glucosyl transferase (UFGT) were expressed, but UFGT expression was only detected
      in berry skin. Similar patterns of expression were observed in the skin of other
      red grapes. In white grapes, UFGT expression was not detected. White grape
      cultivars appear to lack anthocyanins because they lack UFGT, although they also
      had decreased expression of other flavonoid pathway genes.

PMID- 8980507
TI  - A molecular study of dormancy breaking and germination in seeds of Trollius
      ledebouri.
AB  - A cDNA library was generated from seeds of Trollius ledebouri cv. Golden Queen
      after GA3 treatment. Five clones encoded mRNAs which were down-regulated during
      dormancy breaking and the initial stages of germination. Two of these showed
      homology to storage proteins (pPCB3 and pPCB4) and one each to the late
      embryogenesis-abundant (LEA) group 2 dehydrin proteins (pPCB2), a barely glucose
      dehydrogenase (pPCB6) and the glutathione S-transferase (GST) superfamily
      (pPCB7). Transcript levels declined over 8 days in GA3-treated seeds. In dormant
      imbibed seeds transcript levels were relatively unchanged over the same period
      except for the PCB3 transcript, the level of which increased.

PMID- 8980509
TI  - Molecular cloning and characterization of a gene that encodes a MYC-related
      protein in Arabidopsis.
AB  - In plants, MYC-related proteins function as transcription factors involved in
      anthocyanin production and trichome development. We cloned a gene, Atmyc1, and
      its corresponding cDNA, that encodes for a MYC-related protein from Arabidopsis
      thaliana. The putative protein has a basic/helix-loop-helix motif at the C
      terminus and a highly homologous region with that of the maize B/R family at the
      N-terminus. The promoter region of Atmyc1 contains a Sph box (CATGCATG) that is
      known as a cis-regulatory element conferring seed-specific expression. In fact,
      Atmyc1 transcripts were more abundant in developing seeds than in stems and
      leaves where trichomes are normally expressed. Restriction fragment length
      polymorphism mapping demonstrated that Atmyc1 is located on the upper region of
      chromosome 4, which clearly indicates that Atmyc1 is distinct from the ttg
      (transparent testa glabrous) locus that affects both trichome development and
      anthocyanin biosynthesis.

PMID- 8980510
TI  - A 68 bp element of the beta-phaseolin promoter functions as a seed-specific
      enhancer.
AB  - In beans, expression of the beta-phaseolin gene (phas), encoding the major seed
      storage protein of bean (Phaseolus vulgaris) is confined to the cotyledons of
      developing embryos. Phaseolin has not been detected in the endosperm, which
      remains liquid and is lost early in development. However, fusion constructs
      between the phas promoter and the gus-coding region yield expression in both
      embryo and endosperm of developing seeds from transgenic tobacco (Nicotiana
      tabacum) plants. Although elements extending 1470 bp upstream of the
      transcription start site are known to modulate phas expression, the proximal 295
      bp (p295) are sufficient to drive high levels of seed-specific GUS activity. This
      region was dissected into three elements: a 68 bp element (seed specific
      enhancer, SSE: -295 to -227), a middle region (-227 to -109) and a basal phas
      promoter (-109 to +20: p109). Different promoter constructs containing the SSE or
      middle region upstream of p109 or a CaMV 35S basal promoter (-64 to +6) were
      fused to gus. Each construct was expressed in seed, but not in vegetative
      tissues. Use of the various phas promoter regions yielded notable differences in
      relative GUS activity in embryo or endosperm. Addition of both the SSE and middle
      region resulted in higher activity than the sum of adding either element alone to
      p109, indicating synergistic interaction between these elements. Seeds from
      plants transformed with the proximal 227 bp of promoter (p227) showed embryo
      specific GUS activity. In contrast, constructs containing two copies of the SSE
      element were preferentially expressed in the endosperm. These results illustrate
      the modular nature of the proximal phas promoter, where distinct elements
      contribute to high levels of expression in different parts of the seed.

PMID- 8980511
TI  - Phytochrome of the green alga Mougeotia: cDNA sequence, autoregulation and
      phylogenetic position.
AB  - A cDNA clone encoding phytochrome (apoprotein) of the zygnematophycean green alga
      Mougeotia scalaris has been isolated and sequenced. The clone consisted of 3372
      bp, encoded 1124 amino acids, and showed strainspecific nucleotide exchanges for
      M. scalaris, originating from different habitats. No indication was found of
      multiple phytochrome genes in Mougeotia. The 5' non-coding region of the
      Mougeotia PHY cDNA harbours a striking stem-loop structure. Homologies with
      higher-plant phytochromes were 52-53% for PHYA and 57-59% for PHYB. Highest
      homology scores were found with lower-plant phytochromes, for example 67% for
      Selaginella (Lycopodiopsida), 64% for Physcomitrella (Bryopsida) and 73% for
      Mesotaenium (Zygnematophyceae). In an unrooted phylogenetic tree, the position of
      Mougeotia PHY appeared most distant to all other known PHYs. The amino acids Gly
      Val in the chromophore-binding domain (-Arg-Gly-Val-His-Gly-Cys-) were
      characteristic of the zygnematophycean PHYs known to date. There was no
      indication of a transmembrane region in Mougeotia phytochrome in particular, but
      a carboxyl-terminal 16-mer three-fold repeat in both, Mougeotia and Mesotaenium
      PHYs may represent a microtubule-binding domain. Unexpected for a non-angiosperm
      phytochrome, its expression was autoregulated in Mougeotia in a red/far-red
      reversible manner: under Pr conditions, phytochrome mRNA levels were tenfold
      higher than under Pfr conditions.

PMID- 8980512
TI  - Structure and regulation of the maize Bronze2 promoter.
AB  - The maize Bronze2 (Bz2) gene encodes a glutathione S-transferase that is required
      for anthocyanin pigment accumulation. Two classes of regulatory proteins, R and
      C1, are required for transcriptional activation of Bz2 and several additional
      structural genes. Functional domains of the Bz2 promoter were identified using
      Bz2 promoter-driven luciferase reporter genes electroporated into maize
      protoplasts together with R and C1 expression plasmids. Complete regulation was
      conferred by 224 nt of the Bz2 promoter. Within this region at least two
      separable regions are independently capable of conferring regulation by R and C1.
      Predicted regulatory elements corresponding to two classes of sequence motifs,
      the Myb-box homologous 'C1-motif', TAACTG/CAGTTA, and the G-box and E-box
      homologous 'R-motif', CACGTG, were shown to be important for full R and C1
      activation of the Bz2 promoter. Expression of reconstructed Bz2 genes with
      mutated promoters was quantified using RNase protection, and this analysis
      confirmed results obtained using reporter genes.

PMID- 8980513
TI  - Engineering of the aspartate family biosynthetic pathway in barley (Hordeum
      vulgare L.) by transformation with heterologous genes encoding feed-back
      insensitive aspartate kinase and dihydrodipicolinate synthase.
AB  - In prokaryotes and plants the synthesis of the essential amino acids lysine and
      threonine is predominantly regulated by feed-back inhibition of aspartate kinase
      (AK) and dihydrodipicolinate synthase (DHPS). In order to modify the flux through
      the aspartate family pathway in barley and enhance the accumulation of the
      corresponding amino acids, we have generated transgenic barley plants that
      constitutively express mutant Escherichia coli genes encoding lysine feed-back
      insensitive forms of AK and DHPS. As a result, leaves of primary transformants
      (T0) exhibited a 14-fold increase of free lysine and an 8-fold increase in free
      methionine. In mature seeds of the DHPS transgenics, there was a 2-fold increase
      in free lysine, arginine and asparagine and a 50% reduction in free proline,
      while no changes were observed in the seeds of the two AK transgenic lines
      analysed. When compared to that of control seeds, no differences were observed in
      the composition of total amino acids. The introduced genes were inherited in the
      T1 generation where enzymic activities revealed a 2.3-fold increase of AK
      activity and a 4.0-9.5-fold increase for DHPS. T1 seeds of DHPS transformants
      showed the same changes in free amino acids as observed in T0 seeds. It is
      concluded that the aspartate family pathway may be genetically engineered by the
      introduction of genes coding for feed-back-insensitive enzymes, preferentially
      giving elevated levels of lysine and methionine.

PMID- 8980514
TI  - The same nuclear proteins bind to the 5'-flanking regions of genes for the rice
      seed storage protein: 16 kDa albumin, 13 kDa prolamin and type II glutelin.
AB  - Expression of rice seed storage-protein genes is dramatically regulated over a
      short period of seed maturation. To characterize the expression mechanism of the
      rice seed storage protein genes, their expression of major storage protein genes
      (16 kDa albumin, 13 kDa prolamin and type II glutelin) were compared by RNA blot
      analysis. Their coordinate expression suggests that the transcriptional
      regulatory machinery is shared among the glutelin, prolamin and albumin-genes. We
      isolated two novel genomic genes for prolamins (PG5a and PG5b) and obtained the
      promoter region of the glutelin gene by PCR. The 5'-flanking regions of these
      three rice seed storage protein genes were found to contain some similar
      conserved sequences. Nuclear extract partially purified from maturing rice seeds
      was used for the gel shift assay of the 5' region of the RA gene. We identified
      two DNA sequences of RA gene which were recognized by independent DNA-binding
      proteins. The complexes of these DNA sequences and DNA-binding proteins were
      inhibited by the fragments containing the 5' regions of the prolamin and glutelin
      genes, suggesting that these three genes share transcription factors.

PMID- 8980515
TI  - GSBF1, a seedling-specific bZIP DNA-binding protein with preference for a 'split'
      G-box-related element in Brassica napus RbcS promoters.
AB  - Promoters of RbcS genes may contain a GS-box, which is a cis element with a core
      sequence related to the G-box, but split by a spacer of about 14 bp. Here we
      describe GSBF1, a DNA-binding protein that specifically interacts with a GS-box
      element located proximal to the G-box in the Brassica napus RbcS IV promoter.
      Sequence analysis of GSBF1 revealed a basic region/leucine zipper (bZIP) domain
      that displays structural features distinct from that of G-box binding factors
      (GBFs). Gel shift experiments showed that recombinant GSBF1 does not efficiently
      bind to the continuous G-box motif. RNA gel blot analysis indicated that GSBF1
      transcripts are cotyledon-specific and accumulate to the highest levels during
      late seedling development in a ligh-dependent manner. During the same time
      period, RbcS IV transcript levels decreased simultaneously, suggesting that GSBF1
      acts as a developmental, stage-specific, negative regulator of RbcS IV gene
      expression in rape seedlings.

PMID- 8980516
TI  - Cloning and developmental/stress-regulated expression of a gene encoding a tomato
      arabinogalactan protein.
AB  - Arabinogalactan proteins (AGPs) represent a major class of plant hydroxyproline
      rich glycoproteins (HRGPs) and are components of cell walls and plasma membranes.
      AGPs are thought to play roles in cell differentiation, development, and cell
      cell interactions. Using a synthetic DNA oligonucleotide based upon an amino acid
      sequence motif common to AGPs from Lolium, rose, and carrot (i.e., Hyp-Ala-Hyp
      Ala-Hyp), we have isolated and sequenced the first AGP gene from a partial Sau3A
      tomato genomic library packaged in bacteriophage charon 35. The deduced 215 amino
      acid protein contains 20% Ala, 22% Pro, 10% Gly, and 11% Ser and consists of two
      Pro-Ala-Pro-Ala-Pro pentapeptide repeats and 16 Ala-Pro dipeptide repeats,
      consistent with known AGP amino acid compositions and sequences. Comparison of
      the genomic sequence to a reverse transcribed PCR product and tomato cDNA
      confirmed the AGP gene is expressed and contains one large intervening sequence.
      RNA blot hybridization analysis in tomato indicates this AGP gene is strongly
      expressed in stem and flower, moderately expressed in root and green fruit, and
      weakly expressed in leaves and red fruit as a 980 nucleotide transcript. Five-day
      old seedlings also express this transcript; however, this expression is not
      regulated by light. More significantly, a gradient of AGP gene expression is
      observed in tomato stems, ranging from high levels of expression in young
      internodes to low levels of expression in old internodes. Wounding serves to down
      regulate expression in young and old internodes. Heat shock also affects AGP gene
      expression in stems by transiently down-regulating mRNA levels.

PMID- 8980517
TI  - A novel plasma membrane-bound thioredoxin from soybean.
AB  - Two thioredoxin cDNAs from soybean were isolated by screening an expression
      library using an anti-(plasma membrane) serum. The nucleotide sequences of the
      two cDNAs were found to be 89% identical. The polypeptides encoded by the two
      cDNAs, designated TRX1 and TRX2, contain a disulfide active site, as found in
      other thioredoxins. TRX1 was expressed as a fusion protein in Escherichia coli
      and shown to possess thiol-disufide interchange activity. Unlike other eukaryotic
      thioredoxins, these two soybean thioredoxins contain a putative transmembrane
      domain in their N-terminal regions. To determine subcellular location, the TRX1
      was fused with a reporter epitope at its C-terminus and expressed in transgenic
      tobacco plants. The fusion protein was co-purified with plasma membrane markers
      1,3 beta-glucan synthase and vanadate-sensitive ATPase, indicating the plasma
      membrane location of TRX1. When the reporter epitope was inserted between the
      start codon and the transmembrane domain in the N-terminus, the fusion protein
      was found in the soluble fraction, possibly due to disruption of the
      transmembrane domain by the highly hydrophilic epitope sequence. Taken together,
      our results demonstrate that soybean TRX1 is a plasma membrane-bound thioredoxin,
      which is most likely anchored to the membrane through the N-terminal
      transmembrane domain. It is known that plant plasma membranes contain various
      proteins with thiol-disulfide interchange activity. The soybean thioredoxins
      reported here are the first group of such proteins to be characterized at the
      molecular level. However, the biological function of the plasma membrane-bound
      thioredoxin remains to be determined.

PMID- 8980518
TI  - Organization and characterization of the ribulose-1,5-bisphosphate
      carboxylase/oxygenase large subunit epsilon N-methyltransferase gene in tobacco.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit (LS)
      epsilon N-methyltransferase (Rubisco LSMT) catalyzes the posttranslational
      methylation of the epsilon-amino group of Lys-14 in the LS of Rubisco in many
      higher plant species including tobacco. The tobacco Rubisco LSMT gene (rbcMT-T)
      and its cDNA were isolated, sequenced, and characterized. The gene contains 6
      exons and spans about 6 kb. Primer extension analysis indicated one transcription
      start site located 93 nt upstream of the translation initiation site. Sequence
      analysis of the 5'-flanking region suggests several potential binding sites for
      transcription factors, including 7 GT-1 elements and an HSP-70.5 element. Gene
      dosage analysis by Southern hybridization demonstrated that the tobacco rbcMT-T
      gene is present as a single copy in the tobacco haploid genome. The full-length
      cDNA for tobacco rbcMT-T is 1974 nt in length excluding the 3' poly(A)15 tail,
      and encodes a 491 amino acid polypeptide with a molecular mass of ca. 56kDa. The
      deduced amino acid sequence of tobacco Rubisco LSMT has 64.5% identity and 75.3%
      similarity with the sequence of pea Rubisco LSMT, and both proteins contain
      several copies of a conserved imperfect leucine-rich repeat motif.

PMID- 8980519
TI  - Three knotted1-like homeobox genes in Arabidopsis.
AB  - Five arabidopsis kn1-like homeobox genes were cloned through low-stringency
      screening of Arabidopsis cDNA libraries with the kn1 homeobox from maize. These
      five genes were named KNAT1-5 (for kn1-like Arabidopsis thaliana). An analysis of
      KNAT1 and 2 has been presented previously [19]. Here we present an analysis of
      the genes KNAT3, 4 and 5. On the basis of sequence and expression patterns, these
      three genes belong to the class II subfamily of kn1-like homeobox genes [16]. Low
      stringency Southern analysis suggests several additional members of the class II
      genes exist in the Arabidopsis genome. The predicted amino acid sequences of the
      three genes share extensive homology outside of the homeodomain, including 84%
      between KNAT3 and KNAT4. Northern analysis shows that although all three genes
      are expressed in all tissues examined, the level of KNAT3 RNA is highest in young
      siliques, inflorescences and roots, KNAT4 RNA level is strongest in leaves and
      young siliques, and KNAT5 RNA level is highest in roots. The specificity of these
      patterns was confirmed by RNA fingerprint analysis. KNAT3 and 4 are light
      regulated as they show reduced expression in etiolated seedlings and also in hy3,
      cop1 and det1 mutant backgrounds.

PMID- 8980520
TI  - A model for the evolution of the plastid sec apparatus inferred from secY gene
      phylogeny.
AB  - Plastids possess a bacteria-like sec apparatus that is involved in protein import
      into the thylakoid lumen. We have analyzed one of the genes essential for this
      process, secY. A secY gene from the unicellular red alga Cyanidium caldarium was
      found to be transcriptionally active, demonstrating for the first time that secY
      is functional in a plastid. Unlike the situation seen in bacteria the C.
      caldarium gene is transcribed monocistronically, despite the fact that it is part
      of a large ribosomal gene cluster that resembles bacterial spc operons. A
      molecular phylogeny is presented for 8 plastid-encoded secY genes, four of which
      have not been published yet. In this analysis plastid secY genes fall into two
      classes. One of these, comprising of genes from multicellular red algae and
      Cryptophyta, clusters in a neighbour-joining tree with a cyanobacterial
      counterpart. Separated from the aforesaid are secY genes from Chromophyta,
      Glaucocystophyta and a unicellular red alga. All plastid and cyanobacterial
      sequences are located on the same branch, separated from bacterial homologues. We
      postulate that the two classes of secY genes are paralogous, i.e. their gene
      products are involved in different protein translocation processes. Based on this
      assumption a model for the evolution of the plastid sec apparatus is presented.

PMID- 8980521
TI  - Characterization of replication origins flanking the 23S rRNA gene in tobacco
      chloroplast DNA.
AB  - Using 5' end-labeled nascent strands of tobacco chloroplast DNA (ctDNA) as a
      probe, replication displacement loop (D-loop) regions were identified. The
      strongest hybridization was observed with restriction fragments containing the
      rRNA genes from the inverted repeat region. Two-dimensional gel analysis of
      various digests of tobacco ctDNA suggested that a replication origin is located
      near each end of the 7.1 kb BamHI fragment containing part of the rRNA operon.
      Analysis of in vitro replication products indicated that templates from either of
      the origin regions supported replication, while the vector alone or ctDNA clones
      from other regions of the genome did not support in vitro replication. Sequences
      from both sides of the BamHI site in the rRNA spacer region were required for
      optimal in vitro DNA replication activity. Primer extension was used for the
      first time to identify the start site of DNA synthesis for the D-loop in the rRNA
      spacer region. The major 5' end of the D-loop was localized to the base of a stem
      loop structure which contains the rRNA spacer BamHI site. Primer extension
      products were insensitive to both alkali and RNase treatment, suggesting that RNA
      primers had already been removed from the 5' end of nascent DNA. Location of an
      origin in the rRNA spacer region of ctDNA from tobacco, pea and Oenothera
      suggests that ctDNA replication origins may be conserved in higher plants.

PMID- 8980523
TI  - A highly sensitive plant hybrid protein assay system based on the Spm promoter
      and TnpA protein for detection and analysis of transcription activation domains.
AB  - TnpA is a multifunctional DNA binding protein encoded by the maize Suppressor
      mutator (Spm) transposable element. TnpA is required for transposition and is a
      repressor of the unmethylated Spm promoter. While analyzing protein domains using
      a yeast GAL4-based hybrid system in transiently transformed tobacco cells, we
      found that TnpA represses the > 10-fold transcriptional activation observed when
      the GAL4 DNA-binding domain is used alone. By contrast, compared to the
      backgroundless TnpA DNA-binding domain alone, 33- to 45-fold activation of the
      Spm promoter was observed when the VP16 activation domain was fused to it. TnpA
      binding sites, but no TATA box, were required for transcription activation. Among
      the TnpA deletion derivatives tested, those retaining the coding sequences for
      the DNA-binding and protein dimerization domains gave the highest level of
      transcription activation when fused with the VP16 activation domain. The TnpA
      gene and TnpA-binding sites in the short Spm promoter therefore provide a novel,
      highly sensitive single-hybrid system for identifying and studying plant
      transcription activation domains in plant cells.

PMID- 8980522
TI  - A family of novel myb-related genes from the resurrection plant Craterostigma
      plantagineum are specifically expressed in callus and roots in response to ABA or
      desiccation.
AB  - A cDNA and two genomic clones comprising highly similar genes that encode a
      protein with a Myb-related DNA-binding domain were isolated from the resurrection
      plant Craterostigma plantagineum. The structure of cpm5 and cpm10 (Craterostigma
      plantagineum myb) genes consists of three putative exons encoding a protein of
      36.6 kDa. The cDNA of cpm7 encodes a closely related protein of 36.8 kDa. The
      canonical Myb domain present in transcriptional activators of yeast, animals and
      plants was localized in the amino terminus of deduced Cpm5, Cpm7 and Cpm10
      proteins and corresponds to the two Myb repeats found in plants. The Myb domain
      of Cpm deduced proteins and a short stretch of amino acids adjacent to this
      region are closely related to a myb gene from Arabidopsis thaliana which is
      expressed in response to osmotic stress and ABA. The rest of the deduced protein
      has no similarity to other reported sequences. The myb-related genes in the
      Craterostigma genome comprise a small gene family of 6-8 members as estimated by
      hybridization with a bona fide Myb domain probe. Northern blot experiments showed
      specific expression of cpm10 in undifferentiated callus tissue up-modulated by
      ABA and expression of cpm7 mRNA in roots up-regulated by dehydration.

PMID- 8980524
TI  - Lysine and threonine metabolism are subject to complex patterns of regulation in
      Arabidopsis.
AB  - To study the regulation of lysine and threonine metabolism in plants, we have
      transformed Arabidopsis thaliana with chimeric genes encoding the two bacterial
      enzymes dihydrodipicolinate synthase (DHPS) and aspartate kinase (AK). These
      bacterial enzymes are much less sensitive to feedback inhibition by lysine and
      threonine than their plant counterparts. Transgenic plants expressing the
      bacterial DHPS overproduced lysine, but lysine levels were quite variable within
      and between transgenic genotypes and there was no direct correlation between the
      levels of free lysine and the activity of DHPS. The most lysine-overproducing
      plants also exhibited abnormal phenotypes. However, these phenotypes were
      detected only at early stages of plant growth, while at later stages, new buds
      emerged that looked completely normal and set seeds. Wild-type plants exhibited
      relatively high levels of free threonine, suggesting that in Arabidopsis AK
      regulation may be more relaxed than in other plants. This was also supported by
      the fact that expression of the bacterial AK did not cause any dramatic elevation
      in this amino acid. Yet, the relaxed regulation of threonine synthesis in
      Arabidopsis was not simply due to a reduced sensitivity of the endogenous AK to
      feedback inhibition by lysine and threonine because growth of wild-type plants,
      but not of transgenic plants expressing the bacterial AK, was arrested in media
      containing these two amino acids. The present results, combined with previous
      studies from our laboratory, suggest that the regulation of lysine and threonine
      metabolism is highly variable among plant species and is subject to complex
      biochemical, physiological and environmental controls. The suitability of these
      transgenic Arabidopsis plants for molecular and genetic dissection of lysine and
      threonine metabolism is also discussed.

PMID- 8980526
TI  - Circadian expression of the carbonic anhydrase gene, Cah1, in Chlamydomonas
      reinhardtii.
AB  - We have investigated whether the expression of carbonic anhydrase genes (Cah1 and
      Cah2) is regulated by a circadian clock in Chlamydomonas. When cells were grown
      in ordinary air under 12 h light/12 h dark (LD) cycles, the levels of the Cah2
      mRNA hardly altered during the cycles, while the Cah1 mRNA showed a strong
      diurnal rhythm. The rhythm of about 24 h continued at least 3 days even under
      continuous light. Temperature compensation of the rhythm was demonstrated, using
      cultures maintained at 16, 22, and 28 degrees C. These results indicate that the
      abundance of the Cah1 transcript is controlled by a circadian clock.

PMID- 8980525
TI  - Chalcone synthase in rice (Oryza sativa L.): detection of the CHS protein in
      seedlings and molecular mapping of the chs locus.
AB  - The chalcone synthase is a key enzyme that catalyses the first dedicated reaction
      of the flavonoid pathway in higher plants. The chs gene and its protein product
      in rice has been investigated. The presence of a chalcone synthase (CHS) protein
      in rice seedlings and its developmental stage-specific expression has been
      demonstrated by western analysis. The chalcone synthase of rice was found to be
      immunologically similar to that of maize. A rice cDNA clone, Os-chs cDNA,
      encoding chalcone synthase, isolated from a leaf cDNA library of an indica rice
      variety Purpleputtu has been mapped to the centromeric region of chromosome 11 of
      rice. It was mapped between RFLP markers RG2 and RG103. RG2 is the nearest RFLP
      marker located at a genetic distance of 3.3 cM. Some segments of chromosome 11 of
      rice including chs locus are conserved on chromosome 4 of maize. The markers,
      including chs locus on chromosome 11 of rice are located, though not in the same
      order, on chromosome 4 of maize. Genetic analysis of purple pigmentation in two
      rice lines, Abhaya and Shyamala, used in the present mapping studies, indicated
      the involvement of three genes, one of which has been identified as a dominant
      inhibitor of leaf pigmentation. The Os-chs cDNA shows extensive sequence
      homology, both for DNA and protein (deduced), to that of maize, barley and also
      to different monocots and dicots.

PMID- 8980527
TI  - Isolation of cDNAs encoding two purine biosynthetic enzymes of soybean and
      expression of the corresponding transcripts in roots and root nodules.
AB  - Soybean nodule cDNA clones encoding glycinamide ribonucleotide (GAR) synthetase
      (GMpurD) and GAR transformylase (GMpurN) were isolated by complementation of
      corresponding Escherichia coli mutants. GAR synthetase and GAR transformylase
      catalyse the second and the third steps in the de novo purine biosynthesis
      pathway, respectively. One class of GAR synthetase and three classes of GAR
      transformylase cDNA clones were identified. Northern blot analysis clearly shows
      that these purine biosynthetic genes are highly expressed in young and mature
      nodules but weakly expressed in roots and leaves. Expression levels of GMpurD and
      GMpurN mRNAs were not enhanced when ammonia was provided to non-nodulated roots.

PMID- 8980528
TI  - Isolation and characterization of cDNA clones corresponding to the genes
      expressed preferentially in floral organs of Arabidopsis thaliana.
AB  - Seventeen cDNA clones of genes corresponding to mRNAs expressed preferentially in
      floral organs of Arabidopsis thaliana were obtained by differential screening of
      a flower bud cDNA library, and classified into five groups (1A, 17A, 1B, 4B and
      5B) by cross-hybridization and restriction analysis. Sequence analysis revealed
      that the 1A-1 and 17A-1 clones encode vegetative storage proteins (VSPs). The VSP
      mRNAs were detected in a small amount in leaves and increased to a limited level
      by wounding. Both 1B-1 and 5B-1 clones were homologous to transmembrane protein
      cDNAs. The protein encoded by 4B-1 clone contained a proline-rich region, but no
      homologous proteins were found in databases.

PMID- 8980529
TI  - Structure and analysis of phospholipase D gene from Ricinus communis L.
AB  - Phospholipase D (PLD; EC 3.1.4.4) has been proposed to play a pivotal role in
      various cellular processes, but molecular understanding of this enzyme is rather
      limited. This report describes the nucleotide sequence, structure, and genomic
      organization of a PLD gene from castor bean (Ricinus communis L. cv. Hale). The
      PLD gene was isolated from a castor bean genomic library using the PLD cDNA as a
      hybridization probe. Sequence comparison with the PLD cDNA revealed that the PLD
      gene consisted of four exons and three introns, one of which interrupts the 5'
      untranslated region. Southern blot analysis indicated that the cloned PLD gene
      was present as a single-copy gene, and yet there were other PLD or PLD-related
      sequences in the castor bean genome.

PMID- 8980531
TI  - Expression analysis of an Arabidopsis C2H2 zinc finger protein gene.
AB  - C2H2 zinc finger protein genes encode nucleic acid-binding proteins involved in
      the regulation of gene activity. AtZFP1 (Arabidopsis thaliana zinc finger protein
      1) is one member of a small family of C2H2 zinc finger-encoding sequences
      previously characterized from Arabidopsis. The genomic sequence corresponding to
      the AtZFP1 cDNA has been determined. Molecular analysis demonstrates that AtZFP1
      is a unique, intronless gene which encodes a 1100 nucleotides mRNA highly
      expressed in roots and stems. A construct in which 2.5 kb of AtZFP1 upstream
      sequences is linked to the beta-glucuronidase gene was introduced into
      Arabidopsis by Agrobacterium-mediated transformation of roots. Histochemical
      analysis of transgenic Arabidopsis carrying the AtZFP1 promoter: beta
      glucuronidase fusion shows good correlation with RNA blot hybridization analysis.
      This transgenic line will be a useful tool for analyzing the regulation of AtZFP1
      to further our understanding of its function.

PMID- 8980532
TI  - Noncoding RNA for CR20, a cytokinin-repressed gene of cucumber.
AB  - The CR20 gene was identified as a cytokinin-repressed gene in excised cotyledons
      of cucumber. We determined the sequences of some CR20 cDNAs with different
      structures and sequenced genomic clones for CR20. This gene consisted of three
      exons, and there were at least three types of transcript, which seemed to be
      generated by alternative splicing of the second intron. None of the CR20
      transcripts included a long open reading frame (ORF). We isolated a cDNA of
      Arabidopsis thaliana with cucumber CR20 cDNA as a probe. This cDNA for a gene
      designated AtCR20-1 also lacked a long ORF. A region of 180 nucleotides was
      conserved in the CR20 RNA of cucumber and the AtCR20-1 RNA of Arabidopsis,
      although the homology was relatively low when the entire sequences were compared.
      Each conserved region consisted of seven elements, and seems to form stable
      secondary structure. These suggest that CR20 RNA may function as an RNA that is
      not translated into a protein.

PMID- 8980530
TI  - Protein stability and degradation in chloroplasts.

PMID- 8980534
TI  - Changes in abundance of an abscisic acid-responsive, early cysteine-labeled
      metallothionein transcript during pollen embryogenesis in bread wheat (Triticum
      aestivum).
AB  - A clone for an embryoid-abundant, early cysteine-labeled metallothionein (EcMt)
      gene has been isolated from a wheat pollen embryoid cDNA library. The transcript
      of this gene was only expressed in embryogenic microspores, pollen embryoids, and
      developing zygotic embryos of wheat. Accumulation of the EcMt mRNA showed a
      direct and positive correlation with an increase of the plant hormone, abscisic
      acid (ABA) in developing pollen embryoids. Treating cultures with an inhibitor of
      ABA biosynthesis, fluridone, suppressed not only ABA accumulation but also the
      appearance of the EcMt gene transcript and the ability of microspores to form
      embryoids. These results suggest that the EcMt gene may act as a molecular marker
      for pollen embryogenesis because ABA biosynthesis is accompanied by the increased
      expression of the EcMt transcript that coincides with the differentiation of
      pollen embryoids in wheat anther cultures.

PMID- 8980533
TI  - A novel type of DNA-binding protein interacts with a conserved sequence in an
      early nodulin ENOD12 promoter.
AB  - The pea genes PsENOD12A and PsENOD12B are expressed in the root hairs shortly
      after infection with the nitrogen-fixing bacterium Rhizobium leguminosarum bv.
      viciae or after application of purified Nod factors. A 199 bp promoter fragment
      of the PsENOD12B gene contains sufficient information for Nod factor-induced
      tissue-specific expression. We have isolated a Vicia sativa cDNA encoding a 1641
      amino acid protein, ENBP1, that interacts with the 199 bp ENOD12 promoter. Two
      different DNA-binding domains were identified in ENBP1. A domain containing six
      AT-hooks interacts specifically with an AT-rich sequence located between
      positions -95 and -77 in the PsENOD12B promoter. A second domain in ENBP1 is a
      cysteine-rich region that binds to the ENOD12 promoter in a sequence non-specific
      but metal-dependent way. ENBP1 is expressed in the same cell types as ENOD12.
      However, additional expression is observed in the nodule parenchyma and meristem.
      The presence of three small overlapping ORFs in the 5'-untranslated region of the
      ENBP1 cDNA indicates that ENBP1 expression might be regulated at the
      translational level. The interaction of ENBP1 with a conserved AT-rich element
      within the ENOD12 promoter and the presence of the ENBP1 transcript in cells
      expressing ENOD12 strongly suggest that ENBP1 is a transcription factor involved
      in the regulation of ENOD12. Finally, the C-terminal region of ENBP1 shows strong
      homology to a protein from rat that is specifically expressed in testis tissue.

PMID- 8980535
TI  - Effects of altered phosphoenolpyruvate carboxylase activities on transgenic C3
      plant Solanum tuberosum.
AB  - Phosphoenolpyruvate carboxylase (PEPC) genes from Corynebacterium glutamicum
      (cppc), Escherichia coli (eppc) or Flaveria trinervia (fppc) were transferred to
      Solanum tuberosum. Plant regenerants producing foreign PEPC were identified by
      Western blot analysis. Maximum PEPC activities measured in eppc and fppc plants
      grown in the greenhouse were doubled compared to control plants. For cppc a
      transgenic plant line could be selected which exhibited a fourfold increase in
      PEPC activity. In the presence of acetyl-CoA, a known activator of the
      procaryotic PEPC, a sixfold higher activity level was observed. In cppc plants
      grown in axenic culture PEPC activities were even higher. There was a 6-fold or
      12-fold increase in the PEPC activities compared to the controls measured in the
      absence or presence of acetyl-CoA, respectively. Comparable results were obtained
      by transient expression in Nicotiana tabacum protoplasts. PEPC of C. glutamicum
      (PEPC C.g.) in S. tuberosum leaf extracts displays its characteristic K(m) (PEP)
      value. Plant growth was examined with plants showing high expression of PEPC and,
      moreover, with a plant cell line expressing an antisense S. tuberosum (anti-sppc)
      gene. In axenic culture the growth rate of a cppc plant cell line was appreciably
      diminished, whereas growth rates of an anti-sppc line were similar or slightly
      higher than in controls. Malate levels were increased in cppc plants and
      decreased in antisense plants. There were no significant differences in
      photosynthetic electron transport or steady state CO2 assimilation between
      control plants and transformants overexpressing PEPC C.g. or anti-sppc plants.
      However, a prolonged dark treatment resulted in a delayed induction of
      photosynthetic electron transport in plants with less PEPC. Rates of CO2 release
      in the dark determined after a 45 min illumination period at a high proton flux
      density were considerably enhanced in cppc plants and slightly diminished in anti
      sppc plants. When CO2 assimilation rates were corrected for estimated rates of
      mitochondrial respiration in the light, the electron requirement for CO2
      assimilation determined in low CO2 was slightly lower in transformants with
      higher PEPC, whereas transformants with decreased PEPC exhibited an appreciably
      elevated electron requirement. The CO2 compensation point remained unchanged in
      plants (cppc) with high PEPC activity, but might be increased in an antisense
      plant cell line. Stomatal opening was delayed in antisense plants, but was
      accelerated in plants overexpressing PEPC C.g. compared to the controls.

PMID- 8980536
TI  - Functional dissection of a bean chalcone synthase gene promoter in transgenic
      tobacco plants reveals sequence motifs essential for floral expression.
AB  - Expression of chalcone synthase (CHS), the first enzyme in the flavonoid branch
      of the phenylpropanoid biosynthetic pathway in plants, is induced by
      developmental cues and environmental stimuli. We used plant transformation
      technology to delineate the functional structure of the French bean CHS15 gene
      promoter during plant development. In the absence of an efficient transformation
      procedure for bean, Nicotiana tabacum was used as the model plant. CHS15 promoter
      activity, evaluated by measurements of beta-D-glucuronidase (GUS) activity,
      revealed a tissue-specific pattern of expression similar to that reported for CHS
      genes in bean. GUS activity was observed in flowers and root tips. Floral
      expression was confined to the pigmented part of petals and was induced in a
      transient fashion. Fine mapping of promoter cis-elements was accomplished using a
      set of promoter mutants generated by unidirectional deletions or by site-directed
      mutagenesis. Maximal floral and root-specific expression was found to require
      sequence elements located on both sides of the TATA-box. Two adjacent sequence
      motifs, the G-box (CACGTG) and H-box (CCTACC(N)7CT) located near the TATA-box,
      were both essential for floral expression, and were also found to be important
      for root-specific expression. The CHS15 promoter is regulated by a complex
      interplay between different cis-elements and their cognate factors. The
      conservation of both the G-box and H-box in different CHS promoters emphasizes
      their importance as regulatory motifs.

PMID- 8980537
TI  - Different sequences for 5'-untranslated leaders of nuclear genes for plastid
      proteins affect the expression of the beta-glucuronidase gene.
AB  - Expression of chimeric uidA gene fusions (for bacterial beta-glucuronidase) with
      5'-flanking sequences of the spinach AtpC and PetE genes (encoding the subunit
      gamma of the chloroplast ATP synthase and plastocyanin, respectively) requires
      sequences for the 5'-untranslated leaders. The sequence for the PetE leader does
      not exhibit significant similarities to those of other leader sequences. Closer
      inspection of PetE uncovered that the crucial region is located in the vicinity
      of the transcription start site (+5/+15, TTGTCATTTCT). In contrast, 3' deletions
      of sequences for the AtpC leader revealed that the region in the vicinity of the
      translation initiation codon is essential for uidA gene expression (+103/+176).
      This segment contains a CT-rich sequence (TTCTCTCTCCT), which is found
      identically or in a slightly modified form in sequences for 85 plant leaders
      deposited in the EMBL data bank. Site-directed mutagenesis of the CT-rich
      sequence resulted in a three-fold reduction of the transcription of the
      transgene. It is concluded (1) that different elements in the sequences for the
      spinach PetE and AtpC leaders control the expression of the uidA gene, (2) that
      these elements operate transcriptionally rather than post-transcriptionally and
      (3) that a CT-rich sequence represents a crucial cis element for the
      transcription of the AtpC::uidA gene fusion.

PMID- 8980538
TI  - A transcriptional analysis of the S1Bn (Brassica napus) family of SINE
      retroposons.
AB  - S1Bn is a plant short interspersed element (SINE) whose amplification probably
      involves the reverse transcription of an RNA intermediate. In this report, we
      identified and characterized S1Bn transcripts from different Brassica napus
      tissues. Despite the presence of a consensus internal POL III promoter in a large
      number of genomic S1Bn elements, we observed that S1Bn transcripts are rare in B.
      napus cells. The use of two very sensitive methods (RT-PCR and RACE PCR) allowed
      the characterization of 102 independent S1Bn cDNA clones from three different
      tissues (shoot, root and callus). From this analysis, we conclude that the
      majority of S1Bn transcripts probably result from a small number of
      cotranscriptional events where an S1Bn element is transcribed due to its presence
      in a POL II transcriptional unit. Specific POL III RNA transcripts, initiating at
      the first 5' nucleotide of the DNA element, are also present in the tested
      tissues and possibly result from the transcriptional activity of as few as three
      genomic elements. Two of these transcripts could represent master transcripts
      responsible for the amplification of S1Bn subfamilies. We also observed that the
      population of specific POL III transcripts varies among the three tested tissues
      and that some transcripts appear completely tissue-specific.

PMID- 8980540
TI  - New potential markers of in vitro tomato morphogenesis identified by mRNA
      differential display.
AB  - The identification of plant genes involved in early phases of in vitro
      morphogenesis can not only contribute to our understanding of the processes
      underlying growth regulator-controlled determination, but also provide novel
      markers for evaluating the outcome of in vitro regeneration experiments. To
      search for such genes and to monitor changes in gene expression accompanying in
      vitro regeneration, we have adapted the mRNA differential display technique to
      the comparative analysis of a model system of tomato cotyledons that can be
      driven selectively toward either shoot or callus formation by means of previously
      determined growth regulator supplementations. Hormone-independent transcriptional
      modulation (mainly down-regulation) has been found to be the most common event,
      indicating that a non-specific reprogramming of gene expression quantitatively
      predominates during the early phases of in vitro culture. However, cDNA fragments
      representative of genes that are either down-regulated or induced in a programme
      specific manner could also be identified, and two of them (G35, G36) were further
      characterized. One of these cDNA fragments, G35, corresponds to an mRNA that is
      down-regulated much earlier in callus- (day 2) than in shoot-determined explants
      (day 6). The other, G36, identifies an mRNA that is transiently expressed in
      shoot-determined explants only, well before any macroscopic signs of
      differentiation become apparent, and thus exhibits typical features of a
      morphogenetic marker.

PMID- 8980542
TI  - Genetic similarity among Arabidopsis thaliana ecotypes estimated by DNA sequence
      comparison.
AB  - DNA polymorphisms among Arabidopsis thaliana ecotypes are widely used as genetic
      markers in map-based cloning strategies. New PCR-based molecular markers do not
      only facilitate molecular mapping, but can also be used to obtain reliable
      sequence information for cladistic analyses. We have used CAPS (cleaved amplified
      polymorphic sequences) markers and a direct sequencing strategy to estimate
      genetic similarity among eighteen Arabidopsis ecotypes. Sequences at four loci,
      two from the nuclear and two from a non-nuclear genome, were analysed. For each
      ecotype more than 1000 bp of sequence information was obtained, and genetic
      similarity was calculated from a total of 35 polymorphic sites using a character
      based approach. Divergence ranged from zero up to 50 discordant characters among
      the 72 characters defined by the polymorphisms. Separate calculations based on
      the nuclear and the non-nuclear sequences were performed and revealed a number of
      common features, including the existence of small clusters of very closely
      related ecotypes separated from each other by extensive sequence divergence. Our
      results provide information useful especially to investigators setting up crosses
      for chromosome landing strategies.

PMID- 8980541
TI  - Single-site manipulation of tomato chromosomes in vitro and in vivo using Cre-lox
      site-specific recombination.
AB  - With the aim of developing new techniques for physical and functional genome
      analysis, we have introduced the Cre-lox site-specific recombination system into
      the cultivated tomato (Lycopersicon esculentum). Local transposition of a Ds(lox)
      transposable element from a T-DNA(lox) on the long arm of chromosome 6 was used
      to position pairs of lox sites on different closely linked loci. In vitro Cre-lox
      recombination between chromosomal lox sites and synthetic lox oligonucleotides
      cleaved the 750 Mb tomato genome with 34 bp specificity to release unique 65 kb
      and 130 kb fragments of chromosome 6. Parallel in vitro experiments on
      Saccharomyces cerevisiae chromosomes show the efficiency of cleavage to be 50%
      per chromosomal lox site at maximum. By expressing the Cre recombinase in tomato
      under control of a constitutive CaMV 35S promoter, efficient and specific somatic
      and germinal in planta inversion of the 130 kb fragment is demonstrated. The
      combined use of in vitro and in vivo recombination on genetically mapped lox
      sites will provide new possibilities for long range restriction mapping and in
      vivo manipulation of selected tomato genome segments.

PMID- 8980539
TI  - Alloplasmic male-sterile Brassica lines containing B. tournefortii mitochondria
      express an ORF 3' of the atp6 gene and a 32 kDa protein. off.
AB  - Analyses of mitochondrial transcription and in organello translation were
      performed with the Brassica tournefortii cytoplasm. This cytoplasm causes
      alloplasmic male sterility when combined with the nuclear genomes of B. napus and
      B. juncea. Mitochondrial RNA and protein banding patterns were compared between
      the fertile wild species B. tournefortii, an alloplasmic male-sterile B. juncea
      line, an alloplasmic male-sterile B. napus line and an alloplasmic B. napus line
      with restored fertility. The analyses were carried out to identify differences in
      gene expression and to investigate whether alterations in gene expression
      accompanied male sterility. A difference in transcription patterns between the
      fertile B. tournefortii and the alloplasmic lines was found for the atp6 gene.
      The atp6 region was investigated further, since a similar alteration in atp6
      transcription has been observed in two other Brassica cytoplasms which are
      associated with cytoplasmic male sterility (CMS). The additional longer atp6
      transcript detected in the alloplasmic lines in the present study was found to
      contain an open reading frame (ORF) located downstream of the atp6 gene. DNA
      sequencing revealed that the ORF, orf263, could encode a protein with a predicted
      molecular weight of about 29 kDa. In organello analysis detected two proteins of
      29 and 32 kDa respectively, which were found only in the alloplasmic lines.
      Furthermore, the 32 kDa protein accompanied male sterility since it was absent in
      alloplasmic plants restored to fertility. The protein analysis might indicate
      that orf263 is translated and causes CMS.

PMID- 8980544
TI  - Expression and functional analysis of Euglena Gracilis chloroplast initiation
      factor 3.
AB  - A portion of a cDNA predicted to encode the mature form of Euglena gracilis
      chloroplast translational initiation factor 3 (IF-3chlM, molecular mass, 46 402)
      and the portion of this factor homologous to bacterial IF-3 (IF-3chlH, molecular
      mass 22 829) have been cloned and expressed in Escherichia coli as histidine
      tagged proteins. The homology domain can be expressed in reasonable levels in E.
      coli. However, IF-3chlM is quite toxic and can only be produced in small amounts.
      Both forms of the chloroplast factor are associated with E. coli ribosomes.
      Purification procedures have been developed for both IF-3chlM and IF-3chlH using
      Ni-NTA affinity chromatography followed by ion exchange chromatography. IF-3chlM
      and IF-3chlH are active in promoting ribosome dissociation and in promoting the
      binding of fMet-tRNA to E. coli ribosomes. However, IF-3chlH has at least 5-fold
      more activity than either native IF-3chl or IF-3chlM in promoting initiation
      complex formation on chloroplast 30S ribosomal subunits in the presence of a mRNA
      carrying a natural translational initiation signal. This observation suggests
      that regions of IF-3chl lying outside of the homology domain may down-regulate
      the activity of this factor.

PMID- 8980543
TI  - Molecular characterization of a phosphoenolpyruvate carboxylase in the gymnosperm
      Picea abies (Norway spruce).
AB  - Phosphoenolpyruvate carboxylase (PEPC) genes and cDNA sequences have so far been
      isolated from a broad range of angiosperm but not from gymnosperm species. We
      constructed a cDNA library from seedlings of Norway spruce (Picea abies) and
      identified cDNAs coding for PEPC. A full-length PEPC cDNA was sequenced. It
      consists of 3522 nucleotides and has an open reading frame (ORF) that encodes a
      polypeptide (963 amino acids) with a molecular mass of 109551. The deduced amino
      acid sequence revealed a higher similarity to the C3-form PEPC of angiosperm
      species (86-88%) than to the CAM and C4 forms (76-84%). The putative motif
      (Lys/Arg-X-X-Ser) for serine kinase, which is conserved in all angiosperm PEPCs
      analysed so far, is also present in this gymnosperm sequence. Southern blot
      analysis of spruce genomic DNA under low-stringency conditions using the PEPC
      cDNA as a hybridization probe showed a complex hybridization pattern, indicating
      the presence of additional PEPC-related sequences in the genome of the spruce. In
      contrast, the probe hybridized to only a few bands under high-stringency
      conditions. Whereas this PEPC gene is highly expressed in roots of seedlings, a
      low-level expression can be detected in cotyledons and adult needles. A molecular
      phyiogeny of plant PEPC including the spruce PEPC sequence revealed that the
      spruce PEPC sequence is clustered with monocot and dicot C3- form PEPCs including
      the only dicot C4 form characterized so far.

PMID- 8980545
TI  - Application of differential display RT-PCR to the analysis of gene expression in
      a plant-fungus interaction.
AB  - Establishment of a plant-pathogen interaction involves differential gene
      expression in both organisms. In order to isolate Botrytis cinerea genes whose
      expression is induced during its interaction with tomato, a comparative analysis
      of the expression pattern of the fungus in planta with its expression pattern
      during in vitro culture was performed by differential display of mRNA (DDRT-PCR).
      Discrimination of fungal genes induced in planta from plant defense genes induced
      in response to the pathogen was attempted by including in this comparative
      analysis the expression patterns of healthy tomato leaves and of tomato leaves
      infected with two different pathogens, either Rhytophthora infestans or tobacco
      necrosis virus (TNV). Using a limited set of primer combinations, three B.
      cinerea cDNA fragments, ddB-2, ddB-5 and ddB-47, were isolated representing
      fungal genes whose expression is enhanced in planta. Northern blot analysis
      showed that the transcripts detected with the cDNA clones ddB-2 and ddB-5
      accumulated at detectable levels only at late time points during the interaction.
      The cDNA clone ddB-47 detected two different sizes of transcripts displaying
      distinct, transient expression patterns during the interaction. Sequence analysis
      and database searches revealed no significant homology to any known sequence.
      These results show that the differential display procedure possesses enough
      sensitivity to be applied to the detection of fungal genes induced during a plant
      pathogen interaction. Additionally, four cDNA fragments were isolated
      representing tomato genes induced in response to the infection caused by B.
      cinerea, but not by P. infestans.

PMID- 8980546
TI  - The heat shock cognate 80 gene of tomato is flanked by matrix attachment regions.
AB  - Matrix attachment regions (MARs) are thought to participate in the organization
      and segregation of independent chromosomal loop domains. Although there are
      several reports on the action of MARs in the context of heterologous genes,
      information is more limited on the role of MARs associated with plant genes.
      Transgenic studies suggest that the upstream, intron and downstream regions of
      the developmentally regulated heat shock cognate 80 gene (HSC80) of tomato
      participate in chromatin organization. In this study, we tested the in vitro
      affinity of the HSC80 gene to chromosomal scaffolds prepared from shoot apices of
      tomato. We found that a 1.5 kb upstream region and a 1.4 kb downstream region,
      but not the intron region, are MARs. These MARs interact with tomato and pea
      scaffolds and bind regardless of the expression status of HSC80 in the tissue
      from which the nuclei were isolated. Comparison to two known yeast MARs, ARS1 and
      CENIII, showed that the HSC80 5'MAR binds more avidly to tomato scaffolds than
      ARS1, while no binding of CENIII was observed. Competition binding between the
      two HSC80 MARs indicated that the 5'MAR can outcompete the 3'MAR and not vice
      versa. Last, we observed that the interaction of the 3'MAR with the scaffold
      could result in an electrophoretic mobility shift resistant to SDS, protease, and
      phenol treatment. In conclusion, MARs whose binding properties can be clearly
      differentiated are closely flanking the HSC80 gene. The discovery of MARs in
      regions which have a distinct function in HSC80 transgenes but not in transient
      expression assays, is consistent with a chromosomal scaffold role in HSC80 gene
      regulation.

PMID- 8980547
TI  - CP12: a small nuclear-encoded chloroplast protein provides novel insights into
      higher-plant GAPDH evolution.
AB  - Higher-plant chloroplast NAD(P)-glyceraldehyde 3-phosphate dehydrogenase (NAD(P)
      GAPDH; EC 1.2.1.13) is composed of two different nuclear-encoded subunits, GAPA
      and GAPB, forming the highly active heterotetrameric A2B2 enzyme. The main
      difference between these two subunits is a C-terminal extension of about 30 amino
      acid residues of GAPB. We present cDNA clones for a nuclear-encoded chloroplast
      protein from pea, spinach and tobacco, which we have named CP12. The mature
      protein consists of only 74, 75 and 76 amino acid residues, respectively and
      contains two domains with significant homology to the C-terminal extension of
      GAPB. Affinity chromatography approaches reveal also a specific interaction
      between CP12 and chloroplast GAPDH. Northern blot analysis indicates that CP12
      is, like plastid GAPDH, expressed in green and also in etiolated leaves. Further
      homology is observed between CP12 and ORF3, an open reading frame located in the
      hox gene cluster of Anabaena variabilis. This gene cluster encodes the subunits
      of the bidirectional NADP(+)-dependent [NiFeS] dehydrogenase. We propose
      therefore a common evolutionary origin of CP12 and higher-plant chloroplast GAPDH
      subunit GAPB from the cyanobacterial ORF3.

PMID- 8980548
TI  - Expression of single-chain antibody fragments (scFv) specific for beet necrotic
      yellow vein virus coat protein or 25 kDa protein in Escherichia coli and
      Nicotiana benthamiana.
AB  - The coding sequences for the variable regions of heavy and light chains of
      monoclonal antibodies (mAbs) to beet necrotic yellow vein virus (BNYVV) coat
      protein (cp) or the 25 kDa nonstructural protein (P25) were cloned into the pCOCK
      vector and expressed as single-chain antibody fragments (scFv) in Escherichia
      coli. For expression in higher plants the scFv were targeted either to the
      secretory pathway by including the sequences encoding the pectate lyase B (PelB)
      or the phytohemagglutinin (PHA) signal peptides in the vector constructs or they
      were targeted to the cytoplasm by omitting a signal peptide-encoding sequence
      from the constructs. The scFv were detected mainly in plants in which the PHA
      signal peptide had been used for targeting demonstrating for the first time the
      usefulness of this peptide for enabling scFv expression in plants. The scFv were
      not secreted into the culture fluids of suspension cultures, but were retained in
      the cells. The amount of expression of scFv in the best expressing plants was at
      least as high as in bacterial culture supernatants. In a dot blot immunoassay,
      0.4 ng BNYVV cp or 0.8 ng P25 were detected by the respective scFv either from E.
      coli or from plants. The majority of the 21 plants expressing cp-specific scFv
      had near-normal growth whereas the three plants expressing P25-specific scFv grew
      poorly and did not form roots.

PMID- 8980549
TI  - Identification of a light-regulated MYB gene from an Arabidopsis transcription
      factor gene collection.
AB  - Seven different MYB-related genes have been isolated from a genomic Arabidopsis
      library with probes based on MYB DNA-binding motifs. The predicted amino acid
      sequence of these genes showed high similarity in the MYB domain but outside this
      region virtually no similarities were found. The set of MYB-related genes was
      used to identify differentially expressed genes following the transfer of
      etiolated seedlings to light. This differential screen resulted in the selection
      of the ATM4 gene which is induced by light within one hour of exposure of
      etiolated or dark-adapted seedlings.

PMID- 8980551
TI  - Control of industrial noise and hearing loss at work--are we making progress?

PMID- 8980550
TI  - Molecular cloning and expression of the hot pepper ERabp1 gene encoding auxin
      binding protein.
AB  - The 22 kDa auxin-binding proteins in higher plants have received considerable
      attention as candidates for an auxin receptor. A cDNA clone Ca-ERabp1 of hot
      pepper (Capsicum annum) was isolated using the oligonucleotides as PCR primers.
      The cDNA codes for a polypeptide related to the major 22 kDa auxin-binding
      protein from maize and Arabidopsis ERabp1. The deduced amino acid sequence
      contains an endoplasmic reticulum retention signal, the KDEL sequence located at
      the C-terminal end, and has two possible auxin-binding sites, HRHSCE and
      YDDWSVPHTA conserved sequences. Northern hybridization analysis revealed that the
      Ca-ERabp1 gene is differentially expressed in total RNA isolated from different
      organs of a pepper plant, showing the highest level of expression in fruits but
      barely detectable in leaves and roots.

PMID- 8980552
TI  - The essential role of plastic surgery in the new South Africa.

PMID- 8980553
TI  - An impression of the future of academic and tertiary medicine in the new South
      Africa.

PMID- 8980554
TI  - Lessons from an academic comprehensive primary health care centre.

PMID- 8980555
TI  - A community-based distribution strategy for family planning.

PMID- 8980556
TI  - Smoking status, knowledge of health effects and attitudes towards tobacco control
      in South Africa.
AB  - OBJECTIVE: To provide data on the South African adult population's smoking
      status, their knowledge of the health effects of tobacco and their attitudes
      towards tobacco control in South Africa. METHODOLOGY: A national representative
      sample of 2,238 adult (> 18 years) South Africans was surveyed by means of an
      interviewer-administered questionnaire. RESULTS: Thirty-four per cent of adult
      South Africans smoke (52% male, 17% female). There were notable differences in
      gender smoking rates for Indians (61% of men and only 7% of women smoke) and
      blacks (53% of men and 10% of women smoke) but not for coloureds (58% of men and
      59% of women smoke). Provinces with the highest smoking rates are the Northern
      Cape (55%), Western Cape (48%) and North-West (46%). Forty-eight per cent of
      respondents reported that at least one household member smoked. The majority of
      the respondents (87%) acknowledged the harmful effects of direct smoking. Fifty
      eight per cent were aware that cancer is associated with smoking but only 36%
      associated heart disease with smoking. Sixty per cent of the respondents have
      tried to quit at least once for reasons such as the protection of their own
      health, the expense of tobacco products and because of a medical doctor's advice.
      Confusion existed with regard to the effects of the cigarette constituents
      described on cigarette packages. Forty-two per cent of adults incorrectly
      indicated that nicotine causes cancer while 28% correctly indicated that it
      causes addiction, and 44% correctly indicated that condensate causes cancer.
      There is substantial support for a total ban of tobacco advertising on radio
      (61%), for local authorities to regulate smoking in public places (78%), for
      government assistance to farmers for tobacco crop replacement (53%) and for an
      increase in tobacco excise tax if the money is used for health purposes (50%).
      CONCLUSION: The extremely high proportion of both male and female coloured
      smokers is a cause for concern and requires prompt action. Knowledge of the
      specific effects of tobacco in respect of active and passive smoking needs to be
      improved and this could be a first step towards facilitating behaviour change.
      The public support that exists for stronger measures against tobacco use,
      promotion, pricing and growing provides many opportunities for health promotion
      action.

PMID- 8980557
TI  - An investigation into the prescribing of analgesics.
AB  - OBJECTIVE: To investigate the prescribing of analgesic agents in a defined South
      African patient population. DESIGN: Retrospective drug utilisation study.
      SETTING: Prescribing behaviour of a sample of 50 dispensing doctors in Port
      Elizabeth. Data were obtained from a medical aid which used a formulary system.
      MAIN OUTCOME MEASURES: Percentage of central nervous system drugs that analgesics
      comprised; proportion of patients using combination analgesics; cost of
      analgesics. RESULTS: On average, 83.3% of all central nervous system drugs
      dispensed were analgesic agents. These agents represented 70.9% of the total cost
      of central nervous system drugs. A high percentage (82.2%) of the analgesic
      agents dispensed were combination or polycomponent analgesics. The combination
      analgesic tablet, consisting of paracetamol, meprobamate, caffeine and codeine
      phosphate, was the most frequently prescribed central nervous system drug. This
      product accounted on average for 40.4% of all analgesics dispensed. Nearly half
      (46.0%) of all the analgesics dispensed by the sample of doctors were available
      without a prescription. CONCLUSION: The high prescribing rate of combination
      analgesic prescription was a cause for concern, given the dependence-producing
      potential of some of the ingredients, e.g. meprobamate. The prescribing and use
      of analgesics should be carefully monitored by further drug utilisation studies
      in light of the serious adverse effects, such as analgesic nephropathy,
      associated with the longterm use of these agents.

PMID- 8980558
TI  - A drug utilisation study investigating prescribed daily doses of hypolipidaemic
      agents.
AB  - OBJECTIVES: To estimate average prescribed daily doses (PDDs) for selected
      hypolipidaemic agents available on the South African market. Comparison of the
      estimated PDDs with established DDDs (defined daily doses) and international
      dosage ranges. To investigate the age and gender of the users of the different
      hypolipidaemic drugs and drug groups. DESIGN: Retrospective drug utilisation
      study using data from an organisation involved in the pre-certification of
      chronic medication. SETTING: Doctors and patients in South Africa. Participants.
      A total of 2,336 patients of various medical aids who were using cholesterol
      lowering medication on a chronic basis. OUTCOME MEASURES: The PDDs, for the
      complete sample and for the age and gender groups. RESULTS: More than 90% of all
      hyperlipidaemic patients in the study were treated with HMG CoA reductase
      inhibitors or fibrates. The average PDDs for the three most frequently prescribed
      lipid-lowering drugs were 414.4 mg for bezafibrate, 12.5 mg for pravastatin and
      12.6 mg for simvastatin. The PDDs were on average lower than the established
      DDDs. Differences were observed in the pattern of lipid-lowering drug
      prescriptions for women and men. Male users were on average 3.9 years younger
      than female users. CONCLUSIONS: The PDDs used in the patient population studied
      were within locally and internationally acceptable dosage ranges, but were
      generally lower than established DDDs for lipid-lowering drugs. Prescription
      differences exist between female and male patients and between age groups with
      regard to chronic medication. Further studies should be conducted to investigate
      hypolipidaemic drug prescribing in patients who are not on chronic medication.

PMID- 8980559
TI  - Human papillomavirus in normal cervical smears from Cape Town.
AB  - OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) types in
      South African women with normal cervical cytology and to determine whether our
      results are comparable to what has been found elsewhere in the world. DESIGN:
      Cervical smears were collected from 262 women. SETTING: The Cape Town
      metropolitan area. PARTICIPANTS: A total of 262 women, aged 19-85 years. Eighty
      five women attended the family planning clinic of the Gynaecology Department at
      Groote Schuur Hospital and 177 women consulted private gynaecological practices.
      MAIN OUTCOME MEASURES: The prevalence and types of HPV in 192 women with normal
      cervical cytology. RESULTS: The incidence of HPV DNA in cervical smears from Cape
      Town women with normal cytology was found to be 13% (25/192) using Southern blot
      hybridisation. The types of HPV found in normal cervical tissue from Cape Town
      did not differ significantly from those found elsewhere in the world. Nine per
      cent (17/192) were positive for "high-risk' HPV types which are associated with
      premalignant and malignant cervical lesions. In the age group 20-39 years, 15 of
      92 (16%) were positive for HPV DNA, while in the age group above 39 years, 3 of
      53 (6%) women were positive for HPV DNA. CONCLUSIONS: In this study, 25 of 192
      (13%) women with normal cytology were positive for HPV.

PMID- 8980560
TI  - Vitamin D status of older South Africans.
AB  - OBJECTIVE: To determine the vitamin D status of older coloured' South Africans
      who had not sustained a fracture. DESIGN: Cross-sectional analytic study.
      METHODS: A random sample of 200 non-institutionalised subjects in Cape Town aged
      > or = 65 years was drawn using a two-stage cluster design. Trained fieldworkers
      interviewed subjects to obtain demographic, dietary and lifestyle data, to draw
      fasting blood samples for the analysis of serum 25-hydroxyvitamin D (25(OH)D) and
      other biochemical parameters, and to take anthropometric measurements. RESULTS:
      Seventeen per cent of the subjects (95% CI: 11.4-22.6%) had serum 25(OH)D levels
      in the deficient range for the elderly (< 10 ng/ml); 7.5% (95% CI: 3.6-11.4%) had
      concentrations in the moderately severe range of deficiency (< 8 ng/ml). Sixty
      three per cent of the subjects had raised serum alkaline phosphatase
      concentrations. Regression modelling showed neither a sex difference in 25(OH)D
      levels nor a sex-age interaction; however, a negative association with age was
      found (r = -0.18; P < 0.05). Mean oral vitamin D intake was low (3.6 (SD = 2.7)
      micrograms and 2.8 (SD = 1.7) micrograms for men and women, respectively), but no
      association between dietary vitamin D intake and serum 25(OH)D was found.
      CONCLUSIONS: The prevalence of suboptimal vitamin D status was high. However, the
      interpretation of the data, with regard to bone health, is limited by the cross
      sectional design of the study. Further investigation is required to determine the
      potential benefits of intervention in this age group.

PMID- 8980561
TI  - Bone marrow and chelatable iron in patients with protein energy malnutrition.
AB  - OBJECTIVES: To examine the iron status of malnourished children by comparing bone
      marrow iron deposits in children with protein energy malnutrition with those in
      well-nourished controls, and measuring chelatable urinary iron excretion in
      children with kwashiorkor. DESIGN: Bone marrow iron was assessed histologically
      in postmortem specimens from children with kwashiorkor or marasmus, and from
      controls. Twenty-four-hour urinary iron was measured in children with severe
      kwashiorkor, half of whom received 10 mg/kg of intramuscular desferrioxamine
      (DFO) on admission. SETTING: Red Cross War Memorial Children's Hospital, Cape
      Town. SUBJECTS: Thirteen children with kwashiorkor, 6 with marasmus and 16 well
      nourished children underwent bone marrow examination. Urinary iron excretion was
      assayed in 17 children with kwashiorkor. RESULTS: Stainable iron was present in
      the bone marrow of half the children with kwashiorkor but in only 1 child in each
      of the other groups. The median iron excretion was 945.5 micrograms/24 hours in
      the DFO group compared with 28.5 micrograms/24 hours in the non-DFO group.
      CONCLUSIONS: There is an apparent excess of iron which may predispose to
      bacterial infections and free radical-mediated injury in children with
      kwashiorkor.

PMID- 8980562
TI  - Causes of early neonatal respiratory distress in the former Venda--a community
      based study.
AB  - OBJECTIVE: To determine in a rural black population the incidence of common forms
      of respiratory distress (RD) and low birth weight (LBW), the mortality from RD
      and the perinatal mortality rate (PMR). DESIGN: A prospective study in a context
      in which about 90% of the community's births take place within the health service
      and unwell neonates are transferred to hospital. SETTING: The Donald Fraser
      health ward, Northern Province (then Venda), which serves a population of about
      180,000 through 21 clinics and health centres and a 450-bed hospital. SUBJECTS:
      7,539 infants born alive between 1 February 1992 and 31 January 1993, of whom 48
      developed RD. OUTCOME MEASURES: Hjalmarson's classification of RD, modified for
      local conditions. Criteria depended on clinical signs, chest radiography,
      neutrophil count in blood and gastric aspirate, blood cultures and postmortem
      examination. RESULTS: RD 6.4/1,000 livebirths (95% CI 4.6-8.2); infection
      2.6/1,000 livebirths (95% CI 1.4-3.7); hyaline membrane disease (HMD) 0.9/1,000
      livebirths (95% CI 0.2-1.6); pulmonary maladaptation (transient tachypnoea)
      0.8/1,000 livebirths (95% CI 0.2-1.4); mortality from RD 2.1/1,000 livebirths
      (95% CI 1.1-3.2); incidence of LBW 7.9% (95% CI 7.3-8.5); PMR 19.8/1,000
      livebirths (95% CI 17-23). CONCLUSION: A strikingly low incidence of neonatal RD
      in general and of HMD in particular was found in a rural black population,
      probably related to a low LBW incidence. Infection was the commonest cause of RD.

PMID- 8980563
TI  - The value of routine computed tomography of the brain in the pre-operative
      assessment of patients for carotid endarterectomy.
AB  - OBJECTIVE: To determine the prevalence of brain infarcts and other intracranial
      pathology on computed tomography (CT) in patients with greater than 50% internal
      carotid artery stenosis. DESIGN: Descriptive study of CT findings. SETTING:
      Referral-based cohort at Groote Schuur Hospital. PARTICIPANTS: Sixty-three
      patients aged 40-82 years who had CT of the head prior to carotid endarterectomy.
      MAIN OUTCOME MEASURES: Prevalence of brain infarct in patients presenting with
      transient ischaemic attack (TIA) or stroke, and yield of unsuspected intracranial
      pathology other than ischaemic necrosis. RESULTS: Brain infarcts were diagnosed
      in 54% of patients presenting with TIA and in 73% of patients with stroke. True
      positive CT scans were present in only 19% and 44% of patients with TIA and
      stroke, respectively. A single incidental frontal lobe granuloma, unrelated to
      the patient's clinical presentation, was noted. CONCLUSIONS: In the selected
      group of patients referred for carotid endarterectomy, routine use of CT of the
      head is not indicated and can be reserved for cases with extraordinary clinical
      features.

PMID- 8980564
TI  - Evaluation of reflux oesophagitis with technetium-99m-labelled sucralfate.
AB  - Sucralfate binds with denuded protein to form a stable complex to protect the
      damaged mucosa. By utilising this property, technetium-99m-labelled sucralfate
      can be used to demonstrate ulceration in the upper gastro-intestinal tract. AIM:
      The aim of this study was to evaluate 99mTc-labelled sucralfate in the diagnosis
      of grade II-III reflux oesophagitis. METHODS: Ten patients with endoscopic proof
      of grade II-III reflux oesophagitis and 10 patients with normal findings on
      oesophagoscopy were evaluated after they had swallowed 5 ml 99mTc sucralfate.
      Radionuclide imaging was done until activity in the oesophagus had ceased.
      RESULTS: Retention of activity from 10 minutes up to 1 1/2 hours could be
      demonstrated in 9 patients with endoscopically proven oesophagitis. In the
      control group complete clearance of activity was seen in 7 patients. Gastro
      oesophageal reflux could be demonstrated in 4 patients. CONCLUSION: In conclusion
      we found 99mTc sucralfate to be a sensitive and specific method for the non
      invasive diagnosis of grade II or grade III oesophagitis when compared with
      endoscopy [corrected].

PMID- 8980565
TI  - Controlling tuberculosis.

PMID- 8980568
TI  - The winter 1996 mass immunisation campaign--is it the best strategy for South
      Africa at this time?

PMID- 8980569
TI  - The winter 1996 mass immunisation campaign--is it the best strategy for South
      Africa at this time.

PMID- 8980571
TI  - Postpartum sterilisation at Paarl Hospital--a sudden collapse.

PMID- 8980572
TI  - Preventing complicated malaria.

PMID- 8980573
TI  - HIV confirmation and counselling in the insurance industry.

PMID- 8980574
TI  - Feed the children, not the parasites.

PMID- 8980575
TI  - Child sexual abuse in a rural population.

PMID- 8980576
TI  - Abortion legislation.

PMID- 8980577
TI  - Abortion legislation.

PMID- 8980578
TI  - First International Conference on Rural Medicine.

PMID- 8980579
TI  - Notification--completing the cycle.

PMID- 8980580
TI  - Where Sarafina really failed.

PMID- 8980581
TI  - Prescribing habits of paediatricians in private practice.

PMID- 8980582
TI  - Obese (ob) gene--a misnomer?

PMID- 8980584
TI  - Academic excellence and societal influence in the field of tropical medicine and
      international health.

PMID- 8980583
TI  - Multiple cigarette burn wounds in a chronic paranoid schizophrenic.

PMID- 8980585
TI  - Citation analysis for measuring the value of scientific publications: quality
      assessment tool or comedy of errors?
AB  - The basic concepts of citation analysis and journal impact factors are discussed
      in the light of quality assessment of scientific publications, individual
      scientists and research units. The major controversies concerning this topic are
      addressed: technical limitations, database selectivity, time and discipline
      related biases, language and publication type biases, multiple authorship merits
      and citing motivations. Both positive and negative aspects are put into
      perspective. The authors conclude that citation analysis, even when based on
      journal impact factors, can be a worthwhile criterion for evaluating publication
      records of individual scientists or research units, as long as some of the
      problems discussed are sufficiently taken into account. However, this conclusion
      in no way implies that citation analysis may be considered as the one and only
      evaluation criterion.

PMID- 8980586
TI  - Control strategies for sleeping sickness in Central Africa: a model-based
      approach.
AB  - Vector control and the detection (followed by treatment) of infected individuals
      are the two methods currently available for the control of sleeping sickness. The
      basic reproduction rate of a compartmental model is used to analyse and compare
      the two strategies. The efficiency of each strategy will depend on two
      epidemiologic parameters; the intrinsic contamination rate Q (closely related to
      the index of new contaminations) that captures the potential spread of the
      disease, and the intrinsic removal rate from the first stage (intrinsic to the
      particular trypanosome strain and to the population's susceptibility). The model
      shows that when the intrinsic removal rate is low (that is, when there is a long
      first stage characteristic of an endemic situation) the detection of sick
      individuals is more efficient than vector control. The situation is reversed when
      the removal rate is high (in an epidemic situation). The conclusions of the
      analysis are shown to be in general agreement with results obtained in two
      different sleeping sickness foci of Central Africa.

PMID- 8980587
TI  - In vitro antitrypanosomal activity of African plants used in traditional medicine
      in Uganda to treat sleeping sickness.
AB  - In Uganda, as in many other African countries, herbal treatment of various
      diseases is still common. In the present study, 9 plant species collected from
      Tanzania and Uganda and used by traditional healers in southern-eastern Uganda
      for the treatment of human African trypanosomiasis (sleeping sickness) were
      extracted and screened for their in vitro activity against Trypanosoma brucei
      rhodesiense, one of the two causative agents of sleeping sickness. Eight
      lipophilic extracts of 5 plants revealed very promising antitrypanosomal activity
      with IC50 values below 1 microgram/ml; among them were extracts prepared from
      Albizia gummifera (2), Ehretia amoena (1), Entada abyssinica (2), Securinega
      virosa (1) and Vernonia subuligera (2). Activity with IC50 values between 1 and
      10 micrograms/ml was determined for 15 further extracts. Cytotoxicity of active
      extracts, tested on a human fibroblast cell line (WI-38), was found to be high,
      and therefore selectivity indices resulted in less favourable ranges than those
      for the few commercially available drugs. Nevertheless, the results confirm the
      potential of ethnobotanically selected plants as remedies against sleeping
      sickness and call for phytochemical studies.

PMID- 8980589
TI  - Cytotaxonomic identifications of the Simulium damnosum complex
      (Diptera:Simuliidae) from Nigeria.
AB  - Cytotaxonomic analysis of Simulium damnosum s.l. larvae collected from 23 sites
      across 4 bioclimatic zones in Nigeria revealed the presence of 5 cytospecies (S.
      damnosum s.str., S. sirbanum, S. squamosum, S. yahense and S. soubrense
      (including the Beffa form). The biogeographical distribution of the sibling
      species was mostly similar to that observed further west in the OCP area,
      although geographic cytotaxonomic variation was recorded in S. squamosum, S.
      damnosum s.str. and S. sirbanum. Some aspects of the chemical and physical
      environment of the breeding habitats were investigated.

PMID- 8980588
TI  - Detection of circulating antigens in Gabonese patients with Loa loa filariasis.
AB  - Circulating antigens were detected in sera of Gabonese patients with Loa loa
      filarial infection by co-electrosyneresis (Co-ES). The serum samples selected for
      this study were exposed to rabbit hyperimmune antifilarial antisera and human
      immune antisera: specific arcs were observed in 35/60 filarial patients, of whom
      24/47 were microfilaraemic and 11/13 amicofilaraemic. The identity of rabbit
      hyperimmune antisera and loiasial immune sera was confirmed by the continuity of
      precipitation arcs. These preliminary studies were carried out to develop
      diagnostic tools for loiasis and to study the physiopathology of immune
      complexes.

PMID- 8980590
TI  - Clinical and parasitological responses after up to 6.5 years of ivermectin
      treatment for onchocerciasis.
AB  - There are plans to use mass treatment with ivermectin to clear all Africa of the
      worst ocular and cutaneous effects of onchocerciasis. However, there remains
      uncertainty about the most suitable treatment regimen and the likely effects of
      ivermectin on onchocercal skin disease. We have followed 948 subjects for over 6
      years in a double-blind, randomized, controlled study of ivermectin for
      onchocerciasis in a hyperendemic focus in Sierra Leone. Using an intention-to
      treat analysis we found a microfilarial prevalence of 16% 6 months after up to 4
      annual doses of ivermectin, and 13% prevalence in the group receiving up to 10
      doses of ivermectin at 6-monthly intervals. Microfilarial loads were well
      suppressed in both groups, but repopulation data suggest that adult female worms
      are still alive and fecund, strongly underlining the need to continue treatment.
      A clear effect of ivermectin was demonstrated on itching, with about one-third of
      cases being alleviated. Significant reductions in the prevalence of serious
      hyperkeratosis, and possibly dyspigmentation (leopard skin), were noted, but not
      for any other onchocercal skin lesion. Six-monthly and annual treatment regimens
      with ivermectin were equally effective in terms of dermatological and
      parasitological impact.

PMID- 8980591
TI  - ParaSight-F test to diagnose malaria in hypo-endemic and epidemic prone regions
      of Vietnam.
AB  - The antigen capture ParaSight-F test was evaluated during a drug sensitivity
      survey in a hypoendemic region of northern Vietnam. When only asexual blood forms
      of P. falciparum were considered, sensitivity of ParaSight-F was 100%,
      specificity 88% (95% CI 95-80%), positive predictive value 68% (95% CI 85-50%)
      and negative predictive value 100%. ParaSight-F proved very convenient for rapid
      screening and selection of patients to enrol in a drug sensitivity study. In
      northern Vietnam, the introduction of the test as a routine diagnostic tool is
      not justified, considering its high cost, the necessity to carry out the
      treatment of presumptive Plasmodium vivax cases and the persistence of positive
      reactions following treatment. However, the test will be a valuable tool in
      remote areas in emergency situations, where rapid confirmation of a P. falciparum
      outbreak is required.

PMID- 8980593
TI  - In vitro susceptibility of Plasmodium falciparum to quinine: relation to parasite
      density and drug distribution in culture fractions.
AB  - We have studied the importance of parasite density (2, 0.2, 0.02 and 0.002%) for
      the in vitro susceptibility of Plasmodium falciparum (F32 strain) to quinine.
      Shorter exposures (< or = 48 hours) only briefly inhibited parasites in wells
      with the highest initial density. Parasites reappeared after 3-5.5 days in wells
      with intermediate (0.2 and 0.02%) and lowest density (0.002%). Longer exposures
      (> or = 72 hours), however, inhibited them for much longer periods and parasites
      did not reappear in most of the wells with the lowest density during the 28 days
      of follow-up. The mean multiplication rate following reappearance was tenfold per
      parasite schizogony cycle. The mean elimination rate per schizogony cycle was
      calculated to be 99.91%. The elimination and multiplication rates were not
      correlated to initial parasite density. The mean ratio between quinine
      concentrations in erythrocytes and medium was 3.6 regardless of quinine
      concentrations and presence of parasites. Mean quinine-free fractions of 36 and
      67% were found from total concentrations of 0.33 and 10.4 mumol/l. We conclude
      that initial parasite density determines the time to reappearance of parasites
      following quinine exposure while the elimination and multiplication rates are
      independent of the initial parasite density, and that quinine protein binding is
      concentration-dependent in vitro and lower than during treatment.

PMID- 8980592
TI  - A comparative study of the efficacies of chloroquine and a pyrimethamine-dapsone
      combination in clearing Plasmodium falciparum parasitaemia in school children in
      Tanzania.
AB  - A randomized study on the in vivo efficacies of chloroquine and a pyrimethamine
      dapsone combination (Maloprim) in clearing P. falciparum parasitaemia was carried
      out in 77 asymptomatic semi-immune schoolchildren in the Kilombero District of
      Tanzania. Children were randomized to receive either chloroquine at a dose of 25
      mg/kg over three days, or Maloprim (6.25 mg pyrimethamine + 50 mg dapsone for
      children under 10 years, and 12.5 mg pyrimethamine + 100 mg dapsone for children
      10 or more years old) as a single dose. Children were followed-up for malaria
      parasitaemia at days 2, 7 and 14 after screening, randomization and treatment.
      The slide positivity rate was lower in the Maloprim group at all cross-sectional
      surveys (23 vs 37% at day 2; 9 vs 20% at day 7; 21 vs 32% at day 14) but none of
      these differences reached statistical significance. No cases in the Maloprim
      group showed RII resistance, whereas in the chloroquine group, 2 cases showed RII
      resistance and a further 2 cases RIII resistance (6%). No major side-effects were
      reported. The combination of pyrimethamine-dapsone appears to be a better choice
      than chloroquine as a chemoprophylactic regimen for malaria in this area.
      Although they need to be confirmed in a larger study, these results may be of
      interest to the policy-makers as well as researchers.

PMID- 8980594
TI  - Chloroquine resistance of Plasmodium falciparum malaria in Ethiopia and Eritrea.
AB  - We report on the first 2 years of operation of a new strategy for treatment for
      P. falciparum malaria patients who were not cured by a standard course of
      chloroquine. Any such patient who returned to a malaria treatment and detection
      post within 2 weeks was treated daily under supervision with chloroquine.
      Patients whose parasitaemia had not decreased below 25% of the initial level by
      day 3 or cleared completely by day 7 were given sulphadoxine/pyrimethamine
      (Fansidar). Of 39824 patients treated initially with chloroquine, 4% returned to
      the malaria post within 2 weeks of treatment; 87% of these were chloroquine
      resistant and treated with Fansidar and 28% of the returning patients were RIII
      resistant. Resistance was associated with geographical area, initial parasite
      density and age. Earlier studies had shown resistance to be confined to border
      areas, but we found that it was highest in the centre of the region, notably in
      the lowlands of the Shewa and Arsi provinces, and lowest in the west. Although
      imported cases have been held responsible for the development of resistance in
      border areas, other factors are likely to be important in the middle of the
      region. The implications of these findings for a treatment policy of P.
      falciparum malaria in the region are discussed.

PMID- 8980595
TI  - Chloroquine resistant Plasmodium vivax malaria in India.
AB  - In India, 1.2-1.5 million new cases of Plasmodium vivax occur each year. These
      cases are successfully treated with 600 mg chloroquine (adult dose). We report
      the results of malaria treatment of a 13-year-old girl from the Indian Oil
      Corporation (IOC), Mathura, India who contracted P. vivax infection. The
      infection failed to respond to 2 cycles of standard chloroquine therapy. The
      concentrations of chloroquine were monitored with high performance liquid
      chromatography (HPLC). The plasma and whole blood chloroquine concentrations were
      260 and 106 micrograms/l respectively, while a 15 micrograms/l plasma
      concentration is considered lethal to P. vivax. Resistance in P. vivax to
      chloroquine was found at the IOC, Mathura.

PMID- 8980596
TI  - Severe falciparum malaria with hyperparasitaemia: management without exchange
      blood transfusion.
AB  - The risk of complication in falciparum malaria is associated with parasite load.
      Drug therapy alone may be insufficient, and blood exchange transfusion is
      indicated when more than 10% of erythrocytes are parasitized with concurrent
      pulmonary, renal, cerebral or haemostatic complications; without complications,
      when the parasitized erythrocytes exceed 30%. The successful use of conventional
      malaria therapy without exchange transfusion in a young woman with severe
      falciparum malaria is reported.

PMID- 8980597
TI  - Deltamethrin-impregnated bednets as an operational tool for malaria control in a
      hyper-endemic region of Burundi: impact on vector population and malaria
      morbidity.
AB  - Within the framework of the National Malaria Control Programme Burundi,
      impregnated bednets were promoted through health care facilities, schools and
      local administration in Nyanza Lac district. The decision to buy a bednet was
      left to the inhabitants and, as a result, coverage rates between 6 and 65% were
      observed at sub-district level. Three intervention regions were specified based
      on the intervention start date. From November 1992 until March 1995, bi-monthly
      parasitological and entomological surveys were carried out in two areas each of
      Region 1 and Region 2. After introduction of impregnated bednets in Region 1 the
      proportions of children under 5 with high parasitaemia were reduced by 42 and 53%
      in the 2 parasitological survey areas, where the average bednet coverages were 55
      and 44% respectively. In the survey areas of Region 2 (control) no significant
      change occurred during the same period. During the second part of the
      intervention from September 1994, when intervention was also operational in
      Region 2, significant decreases in the proportion of high parasitaemia (63 and
      42%) among children under 5 years were obtained in both parasitological survey
      areas of Region 2 (average coverages of 51 and 29%). The positive output of the
      intervention was maintained and even reinforced in the survey areas of Region 1.
      Bednets as a tool for malaria control entail specific problems such as coverage,
      daily use, reimpregnation, and renewal of old and torn nets. Further evaluation
      has to point out the possible shift of the clinical spectrum and the age-specific
      admission of malaria cases to assess the long-term benefit of this control
      method.

PMID- 8980598
TI  - Health education for community-based malaria control: an intervention study in
      Ecuador, Colombia and Nicaragua.
AB  - A malaria study was undertaken in 98 rural communities of the Pacific coast of
      Ecuador (n = 14), Colombia (n = 22) and Nicaragua (n = 62). In-depth interviews
      on people's knowledge and practice regarding malaria aetiology, symptoms and
      treatment were conducted and complemented by formal household interviews. On the
      basis of this information, an educational programme was set up which included the
      training of village health promoters and community workshops organized by the
      health workers and used a set of methods of interactive learning. After the
      baseline survey the communities were paired and randomly allocated to the
      intervention and control groups. Malaria education took place only in the
      intervention communities. At the start of the project people's knowledge about
      malaria-transmitting mosquitoes and malaria symptoms was correct and widespread
      in those areas where the community exposure to formal health services was
      pronounced. However, knowledge of the recommended dose of chloroquine was poor
      everywhere, and self-treatment of malaria episodes deficient. The educational
      intervention achieved a high level of participant satisfaction which was
      expressed in a high and continuous attendance rate at the monthly workshops. The
      knowledge of malaria aetiology and symptoms was 33-61% better in the intervention
      group than in the control group. Knowledge of the recommended doses of
      chloroquine increased significantly (34% in Ecuador, 93% in Colombia but not in
      Nicaragua) and correct use of chloroquine in the treatment of malaria episodes
      also improved (26% in Ecuador, 85% in Colombia). In Nicaragua the results were
      less satisfactory due to the short period of promotional activities and the
      health services' policy of delivering only supervised treatment to the
      population. It is concluded that health education should play a major role in
      malaria control.

PMID- 8980599
TI  - Evaluation of a monoclonal antibody-based sandwich-ELISA for detection of
      circulating Schistosoma japonicum antigen (Sj31/32) in an endemic area of China.
AB  - A sandwich-ELISA specific for 31/32 kDa schistosome proteins was used to trace
      infections in a Chinese population living in a low endemicity area for
      schistosomiasis japonica. The study population included 304 persons for whom
      records were available from 1992 onwards. In 1994, 2 individuals were positive in
      the miracidial hatching assay performed with 30 g of stools. The ELISA gave
      positive results for 8 individuals, including these 2 with active infections. Of
      the remaining 6 ELISA-positive, 5 had excreted eggs and received praziquantel in
      1993 and may have harboured residual worms in 1994. It is concluded that this
      ELISA is able, in a low prevalence situation, to identify the few infected
      individuals.

PMID- 8980600
TI  - First case of Lagochilascaris minor infection in Bolivia.
AB  - Few cases of human infection with Lagochilascaris minor have been reported in the
      literature. They occurred in Central and South America and the Caribbean. We
      describe the first patient with this nematode infection in Bolivia.

PMID- 8980601
TI  - Isolation of Vibrio cholerae O139 from the drinking water supply during an
      epidemic of cholera.
AB  - In mid-1994, the public water supply was investigated in a medium-sized town in
      south India during an epidemic of cholera due to Vibrio cholerae O139. Vibrio
      cholerae O139 was isolated from the public water supply including one of the
      wells supplying the town, the central overhead tank, and domestic taps connected
      to the public supply. Following chlorination, the organism was no longer isolated
      from the water supply and the epidemic subsided. This demonstration of V.
      cholerae O139 in the drinking water supply of a town underlines the need for
      adequate treatment of the water supply.

PMID- 8980602
TI  - Evaluation of the Og4C3 ELISA in Wuchereria bancrofti infection: infected persons
      with undetectable or ultra-low microfilarial densities.
AB  - The recently developed Og4C3 ELISA, which detects circulating Wuchereria
      bancrofti antigen, appears promising for use in epidemiological surveys, but its
      sensitivity is unknown in persons with ultra-low microfilarial densities. We used
      the Og4C3 to test the sera of 282 persons who were microfilaria-positive in 1-16
      ml of blood, 18 persons who were microfilaria-negative but who had
      ultrasonographic or biopsy evidence of adult W. bancrofti infection, and 63
      lifelong residents of a non-endemic area of Brazil. A total of 276 (97.9%)
      persons with detectable microfilaraemia tested positive (optical density >
      0.033). At microfilarial densities of < 1, 1-30, and > 30 microfilariae per ml of
      blood, the sensitivity of the Og4C3 was 72.2, 97.6 and 100%, respectively (chi 2
      test for trend, P < 10(-6)). The assay was positive in 66.7% of amicrofilaraemic
      persons with evidence of adult worm infection and in one (1.6%) of 63 residents
      of the non-endemic area (specificity, 98.4%). Our findings support the
      increasingly widespread use of the Og4C3 for field investigations and
      epidemiological assessments. However, the sensitivity of the assay may be low in
      persons who are microfilaria-negative or with densities of < 1 microfilaria per
      ml.

PMID- 8980603
TI  - Assessment of mouth-to-mask ventilation in resuscitation of asphyxic newborn
      babies. A pilot study.
AB  - The aim of the study was to compare the effectiveness of mouth-to-mask
      ventilation (MM) in neonatal asphyxia with bag-and-mask ventilation (BM). A new
      mouth-to-mask infant resuscitation system was constructed. The study was
      performed in two university clinics with different resources. The KEM Hospital in
      Bombay was well equipped and neonatologists took part in all resuscitations;
      Muhimbili Medical Centre in Dar es Salaam was understaffed and had no physicians
      available at resuscitation. Therefore, different protocols had to be used. In
      Bombay, the study period was limited to 5 minutes. If needed, mask ventilation
      was then replaced by intubation. In Dar es Salaam, MM ventilation was continued
      for up to 10 minutes, the inspiratory pressure was adjusted to 30 cmH2O and the
      ventilation was slow (8-10 breaths/min). In Bombay, 30 babies were allocated to
      the BM and 24 to the MM groups. In Dar es Salaam 56 were in the BM and 64 in the
      MM groups. The results for term babies in Bombay and both term and pre-term
      babies in Dar es Salaam showed no significant differences between the two groups
      of treatment, as determined by Apgar score > or = 4 at 5 and 10 minutes, number
      of babies with their first gasp, heart rate > 130 beats/min or pulse oximeter
      values above 75%, all at 5 minutes. An Apgar score > or = 4 at 5 minutes was
      achieved in more than 75% of all infants, irrespective of treatment. The rates of
      early neonatal mortality and neonatal convulsions did not differ between the two
      methods of resuscitation. In Dar es Salaam, the low respiratory frequency used in
      both groups was associated with a slow increase in heart rate above 130 beats per
      min. This result indicates that further studies will be needed before such slow
      respiratory frequencies are used. We conclude that, if adequate training is
      provided and the respiratory frequency is kept within the normal range, MM
      ventilation is an alternative to assisted ventilation when no bag and mask is
      available. However, further studies are necessary, since this method has proved
      to be tiring and uncomfortable for the resuscitating health personnel.

PMID- 8980604
TI  - Injection practices in Mwanza Region, Tanzania: prescriptions, patient demand and
      sterility.
AB  - This paper describes prescription and sterilization practices in Mwanza Region,
      Tanzania, before the introduction of interventions aiming at reducing HIV
      transmission by injections. Sixty-six health facilities from Mwanza Region were
      included in the study. Data were collected in interviews and questionnaires,
      through structured observation, bacteriological culture and record analysis.
      Criteria for avoidable injections were based on recommendations of the Essential
      Drugs Programme and on a regional consensus workshop. One in 4 out-patients
      received an injection 70% of which were avoidable. Most were given for acute
      respiratory infections, skin diseases and urinary tract infections. Forty per
      cent of cultures taken from sterilized needles and syringes yielded growth of
      microorganisms. Of 120 patients interviewed most preferred to be treated with
      injections for almost any complaint. Patient demand for injections was felt to be
      a problem in 85% of the health facilities and may have contributed to
      overprescription of injectables. Consensus treatment and sterilization guidelines
      as well as a health education programme were developed and introduced to all
      health workers through seminars.

PMID- 8980605
TI  - Adhesive interactions in hemopoiesis.
AB  - Blood cells developing in the bone marrow exhibit adhesive interactions with
      stromal reticular cells and specialized macrophages, and with several defined
      components of the extracellular matrix. Receptors that are known to participate
      in these interactions include certain integrins, selectins, members of the
      immunoglobulin superfamily, and CD44, and this list may be expected to grow.
      Specific inhibitors of some integrins and of CD44 have been shown to disrupt
      hemopoiesis in vitro; thus the function of adhesive receptors appears critical to
      blood cell development. The capacity of such receptors to transmit signals
      through the plasma membrane suggests that they regulate not just the physical
      interactions of hemopoietic cells, but also the responses of the cells to their
      environment.

PMID- 8980606
TI  - Expression and function of integrins on hematopoietic progenitor cells.
AB  - The growth and differentiation of hematopoietic stem cells are highly dependent
      on regulatory molecules produced by stromal cells of the marrow environment.
      Evidence has accumulated over the past years which shows that adhesive receptors
      on hematopoietic cells and their ligands on stromal cells and extracellular
      matrix play a crucial role in these interactions. Integrins of the beta 1 family,
      mostly VLA-4 and VLA-5, are the best characterized and have been identified on
      committed progenitor cells of the hematopoietic hierarchy as well as on more
      primitive stem cells defined by their long-term repopulating capacity assayed in
      vitro as well as in vivo. Functional assays demonstrate that most progenitor
      cells efficiently bind to ECM components through beta 1 integrins and lineage-
      and maturation stage-specific differences have been described. Evidence exists on
      the direct control of late erythroid differentiation by VLA-4, but whether or not
      the triggering of beta 1 integrins is critically required for hematopoietic stem
      cell functioning at more immature steps is unclear. Many other integrin and non
      integrin receptors involved in adhesive interactions are expressed on
      hematopoietic progenitor cells and tightly regulated during differentiation but
      their function is still controversial. Our main purpose in this review is to
      describe recent advances in the knowledge of integrin expression on hematopoietic
      progenitor cells in both mouse and man. The emerging importance of the synergy
      between integrins and cytokine signalling pathways in the regulation of
      hematopoietic differentiation will also be discussed.

PMID- 8980607
TI  - Expression of an L-selectin ligand on hematopoietic progenitor cells.
AB  - The process of hematopoiesis is dependent on discrete cell-cell and cell-matrix
      interactions which are tightly regulated by expression of adhesion molecules. L
      selectin, an adhesion protein best known for regulating leukocyte attachment to
      endothelium, is characteristically expressed on the earliest hematopoietic
      progenitor cells. Ligands for L-selectin have been extensively characterized on
      endothelial cells. We recently identified a ligand for L-selectin expressed on
      the human hematopoietic progenitor cell line KG1a. This molecule is an integral
      membrane glycoprotein which is structurally different from all ligands previously
      described. We hypothesize that this molecule may mediate L-selectin-specific
      adhesive interactions during hematopoiesis. This article discusses the biology of
      L-selectin and its ligands, and reviews our current understanding of the
      structure and distribution of the L-selectin ligand expressed on hematopoietic
      cells.

PMID- 8980608
TI  - Adhesive proteins and the hematogenous spread of cancer.
AB  - The metastatic spread of cancer is a complex and multistep process characterized
      by a number of biological steps which include the hematogenous and lymphatic
      arrest and adhesion of circulating tumor cells in the vascular bed, invasion of
      tumor cells through the basement membrane, and growth of new tumor colonies in
      the organ parenchyma. In this brief review we describe the role of platelets, the
      hemostatic system, adhesive proteins and their putative receptors in the
      hematogenous dissemination of cancer. The major adhesive proteins postulated to
      play a role in tumor arrest in the vascular bed are thrombospondin-1 (TSP-1),
      laminin, fibronectin and hyaluronan-proteoglycans. The major tumor and vascular
      receptors mediating these adhesive interactions are the CSVTCG-specific TSP-1
      receptor, the 67-kD laminin receptor, the alpha v beta 3 vitronectin/TSP
      1/fibronectin receptor, and CD44 hyaluronan receptor. The discovery of the
      involvement of these adhesive proteins and receptors in the metastatic spread of
      cancer as well as components of the hemostatic system offers unique opportunities
      for the development of antimetastasis therapies for the treatment of cancer.

PMID- 8980609
TI  - Integrin-mediated regulation of hematopoiesis: do BCR/ABL-induced defects in
      integrin function underlie the abnormal circulation and proliferation of CML
      progenitors?
AB  - Hematopoiesis takes place in close contact with the marrow microenvironment.
      Normal progenitors adhere through a variety of receptors to stroma and
      extracellular matrix components, including fibronectin. Adhesion through
      integrins to fibronectin may not only serve to anchor progenitors to the
      microenvironment but also to directly alter the proliferative behavior of normal
      hematopoietic progenitors. Chronic myelogenous leukemia (CML) is a malignant
      disease of the hematopoietic stem cell. At the molecular level, CML is
      characterized by the BCR/ABL gene rearrangement which encodes for the
      oncoprotein, p210bcr-abl. Presence of the p210bcr-abl tyrosine kinase is
      necessary and sufficient for the malignant transformation of hematopoietic cells.
      Clinically, CML is characterized by an abnormal, premature release of primitive
      progenitors and precursors in the blood and by the continuous proliferation of
      the malignant progenitor population. In vitro, CML progenitors fail to adhere to
      or be regulated by marrow stroma. Since CML progenitors express similar numbers
      of integrin adhesion receptors as normal progenitors, functional rather than
      quantitative differences of these receptors on CML progenitors may be responsible
      for the abnormal circulation and proliferation of the malignant clone. In this
      manuscript we will review the role of integrin adhesion receptors present on
      normal hematopoietic progenitors in the regulation of their proliferation and
      discuss signal transduction mechanisms that may be responsible for these effects.
      We will also discuss the integrin defect in CML which may be caused by the
      presence of the oncoprotein, P210bcr-abl, and may explain the abnormal
      trafficking and proliferation observed in CML.

PMID- 8980610
TI  - Expression and function of adhesion receptors in acute myelogenous leukemia:
      parallels with normal erythroid and myeloid progenitors.
AB  - A variety of adhesion receptors are expressed on the blast cells in patients with
      acute myelogenous leukemia. The panel of receptors expressed demonstrates
      heterogeneity just as there is morphologic, histochemical, cytogenetic, and
      molecular genetic variation between various cases of acute myelogenous leukemia.
      The adhesion receptors expressed contain representatives of all the main classes
      of adhesion receptors, but often there is no correlation of the adhesion receptor
      phenotype with the morphologic or clinical features of acute myelogenous
      leukemia. These receptors function in interactions of myelogenous leukemia blasts
      with the cellular and matrix components of the marrow microenvironment, and there
      is evidence that they are involved in blast release from marrow and in homing of
      blasts to extramedullary sites. Evidence is starting to accumulate suggesting
      that adhesive interactions may influence the proliferation and survival of
      leukemic cells, but the precise role that these molecules play in the generation
      and sustenance of the leukemic state remains undetermined.

PMID- 8980612
TI  - Adhesion molecules in the dissemination of non-Hodgkin's lymphomas.
AB  - Most non-Hodgkin's lymphomas (NHLs) express a number of different adhesion
      receptors. A large body of evidence indicates that these adhesion receptors not
      only regulate normal lymphocyte trafficking but also play a pivotal role in the
      dissemination of NHL. Thus, cutaneous lymphocyte antigen, alpha 4 beta 7, alpha E
      beta 7, and L-selectin, which mediate the tissue-specific positioning of normal
      lymphocytes in the skin, mucosa, epithelium and lymph nodes, respectively, are
      selectively expressed on lymphomas localized at these sites. Furthermore,
      expression of CD44, a family of adhesion receptors with pleiotropic effects on
      tumor behavior, is related to lymphoma aggressiveness and dissemination. Taken
      together, these findings offer a framework for the understanding of tumor
      dissemination in NHL. In view of the similarities between lymphocyte behavior and
      the metastatic behavior of solid tumors, these insights might contribute to the
      understanding of the basic mechanisms underlying tumor metastasis in non-lymphoid
      tumors.

PMID- 8980611
TI  - Beta-1-integrin expression in adult acute lymphoblastic leukemia: possible
      relationship with the stem cell antigen CD34.
AB  - In the hemopoietic system, interactions between stem cells and components of the
      bone marrow microenvironment play a pivotal role in blood cell proliferation and
      differentiation. Among the adhesion molecules, the integrins of the beta 1
      subfamily are known to direct cell-cell and cell-matrix interactions and evidence
      has been provided that CD34-positive stem cells bind either to the bone marrow
      stroma or to the extracellular matrix proteins through the beta 1-integrins. It
      seems that changes in their expression pattern or signalling function are likely
      to reflect disturbances at the hemopoietic bone marrow microenvironmental level.
      Any alteration of their biological functions makes them attractive candidates for
      playing decisive roles in the leukemic processes. In this view, beta 1-integrins
      have been recognized to mediate those cellular interactions and migrations that
      are important in the biology of leukemia. In this paper we review some aspects of
      the role played by beta 1-integrins, especially VLA-4 and VLA-5, in adult acute
      lymphoblastic leukemia in relation with the expression rate of the stem cell
      antigen CD34.

PMID- 8980614
TI  - Peripheral blood mobilization of hematopoietic stem cells: cytokine-mediated
      regulation of adhesive interactions within the hematopoietic microenvironment.
AB  - Peripheral blood (PB) mobilization of hematopoietic progenitors, presently
      regarded as an alternative source of cells intended for autologous or allogeneic
      bone marrow (BM) transplantation, supports a role for cytokines in the regulated
      adhesion of hematopoietic compartments to the BM microenvironment. Two major
      consequences might result from cytokine-induced rearrangements of adhesive
      interactions within the hematopoietic tissue, both potentially relevant for
      clinical purposes of PB grafts. The first one, arising from abrogated adhesion of
      hematopoietic stem cells to their microenvironmental 'niche', which is critical
      for the maintenance of cell cycle quiescence and endurability, might result in
      some impairment of the long-term repopulating potential of PB grafts. The second
      and possibly more harmful one is due to the inability of the cytokine to
      distinguish between normal and transformed cells, and would likely result in
      graft contamination by tumor cells, increasing the metastasizing potential of
      hematological malignancies and solid tumors.

PMID- 8980613
TI  - The role of adhesion molecules in multiple myeloma.
AB  - The neoplastic plasma cells of multiple myeloma differ from normal plasma cells
      and other B-cell malignancies by an almost exclusive homing to the bone marrow
      microenvironment which clearly provides the appropriate support, both physical
      and cytokine, to mediate clonal proliferation and terminal differentiation.
      Cellular adhesion molecules are involved in the homing of malignant plasma cells
      to the bone marrow, the production of growth factors and the recirculation of
      these tumour cells in the advanced stages of disease. Neoplastic plasma cells
      express H-CAM (CD44), VLA-4 (CD49d/CD29), ICAM-1 (CD54), N-CAM (CD56) and LFA-3
      (CD58). In addition VLA-5 (CD49e/CD29) expression seems to be related to cells
      with less proliferative potential and more potential for paraprotein production.
      In addition there are fundamental changes in the bone marrow stroma of patients
      with multiple myeloma including altered composition of the extracellular matrix,
      increased growth capability of the cellular elements and increased synthesis of
      interleukin-6 and interleukin-3, which are features postulated to localise and
      promote growth of the circulating neoplastic progenitors in the bone marrow.
      However, the evidence to date does not fully explain the inter-relationship of
      the clonal B cells and the bone marrow stroma in patients with myeloma, including
      factors which trigger and facilitate the extravasation and recirculation of
      neoplastic plasma cells as seen in advanced disease.

PMID- 8980615
TI  - Homing and trafficking of hemopoietic progenitor cells.
AB  - Investigations of the homing of transplanted hemopoietic cells into
      preconditioned recipients have in most studies been referable to parameters that
      determine engraftment. The principles, however, that govern their early traffic
      into the host's blood and tissues have remained much less explored. Early studies
      and experiments from our own laboratory suggest that intravenously administered
      hemopoietic cells, including progenitors, are not selectively taken up by bone
      marrow, as they are distributed widely in several tissues (liver, lung, kidney,
      spleen, bone marrow). As the hemopoietic cells are later on found almost
      exclusively in the bone marrow (and spleen in the mouse), the data argue for
      either preferential retention in these tissues or just only preferential survival
      and proliferation. Our recent studies showing modulation of cells lodged to the
      bone marrow, before proliferation ensues (i.e. 3 h after infusion), would favor
      preferential retainment and/or survival of these cells within the bone marrow.
      Furthermore we established that the VLA4/VCAM-1 adhesion pathway plays a
      significant role in this process, thus defining VCAM-1 as the dominant bone
      marrow endothelial addressin in hemopoietic cell homing. Since homing likely
      represents a cascade of adhesive interactions between hemopoietic cells and bone
      marrow stroma and/or its extracellular matrix, other adhesion pathways are likely
      to be involved and remain to be defined. Finally, our data on mobilization of
      hemopoietic progenitors from normal individuals, induced by blocking the
      VLA4/VCAM-1 adhesion pathway, suggest that the molecular pathways involved in
      homing are also of importance in governing hemopoietic progenitor cell
      trafficking in and out of the bone marrow.

PMID- 8980616
TI  - The role of adhesion and costimulation molecules in graft-versus-host disease.
AB  - A cascade of signaling events directs and regulates the trafficking, homing and
      activation of T lymphocytes after allogeneic transplantation. These adhesion
      receptors include selectins, integrins and adhesion molecules of the
      immunoglobulin superfamily. Tissue-specific homing receptors direct the tissue
      specific trafficking of T lymphocytes. When T cells encounter their antigen(s)
      presented by MHC molecules on APC, the antigen-specific signal mediated through
      the T-cell receptor (TCR) needs to be accompanied by additional costimulatory
      signals for complete T-cell activation to occur. The costimulatory signal
      determines the outcome of the first signal generated through the TCR, leading to
      either complete activation, partial activation or to a long-lasting state of
      antigen-specific unresponsiveness, termed anergy. Complete activation of T cells
      results in IL-2R (CD25) receptor expression, IL-2 production and T-cell
      proliferation.

PMID- 8980617
TI  - Adhesive interactions in hemostasis.
AB  - Adhesion molecules and adhesive interactions play a critical role in the process
      of hemostasis. A vascular rent requires a patch, and this patch must be provided
      from constituents of the cellular and fluid phases of flowing blood, constituents
      that must not interfere with this flow under unperturbed conditions. Platelets,
      the cellular elements of the patch, are inert until they encounter conditions
      that trigger their activation. In response to injury they undergo a rapid and
      dramatic change both in shape and in their surface characteristics, a change that
      allows them to become both the nidus and the stimulus for the precipitation of a
      meshwork of fibrin. The interactions between platelets and exposed collagen in
      the damaged vessel wall, plasma and platelet von Willebrand factor, and plasma
      and platelet fibrinogen can all be considered 'adhesive interactions'.

PMID- 8980618
TI  - Virus-induced autoimmune disease: transgenic approach to mimic insulin-dependent
      diabetes mellitus and other autoimmune diseases.
AB  - The technology of cloning viral genes and expressing them in vivo under cell
      specific promoters allows to dissect the role of viruses, host self proteins,
      host genetics and immune responses in the complex etiology of autoimmune disease.
      Expression of a viral transgene, that is really a marker for a host "self"
      protein per se in beta cells of the islets of Langerhans, need not cause disease.
      In our model, expression of a viral gene was not associated with disease over the
      lifetime of the animal. However, when the host becomes infected with a virus
      encoding the same gene as the transgene or one closely related to it, a resultant
      immune response directed against the virus also recognizes the transgene leading
      to progressive T-cell-mediated response and destruction of the tissue expressing
      the viral ("self") gene, leading to autoimmune disease. This multifactorial
      process is influenced by whether the viral transgene is expressed in the thymus
      as well as in the disease-related cell or target tissue. Thymic expression
      influences negative selection of responder lymphocytes and thus delays the onset
      of the autoimmune disorder. Further, the MHC haplotype or other background genes
      of an individual undergoing autoimmune dysfunction play a role in the affinity of
      binding of the transgene products to the MHC molecule and influence the degree of
      negative selection that occurs, thereby influencing the vigor of the resulting
      immune response. The current ability to express host or viral genes in unique
      cell populations, and to make double- or triple-tg mice in which various cytokine
      genes or lymphocyte activation genes can be expressed along with the viral gene,
      offers a unique possibility for molecular dissection of autoimmunity. With the
      information on hand, approaches to the prevention and treatment of human
      autoimmune disease are likely to be uncovered. Finally, animal models are
      available in which the onset, progression and control of molecular mimicry can be
      evaluated. Future studies should define roles played by cytokines, bystander and
      immune-specific cross-reactivity to viruses and other microbes in several
      autoimmune diseases.

PMID- 8980619
TI  - B- and T-lymphocyte subpopulations in the adenoids of children with otitis media.
AB  - Adenoid hyperplasia is connected with the pathogenesis of otitis media in
      children, as implicated by the residence of pathogens causing otitis media in
      adenoids, and by the beneficial effect of adenoidectomy. We have quantitated the
      proportions of certain T- and B-lymphocyte subsets in the adenoids by three-color
      flow cytometry. Three groups were studied: 1) children with persistent effusion
      in the middle ear (pOME), 2) children with recurrent otitis media with no
      effusion in the middle ear at the time of surgery (rAOM), and 3) children with
      adenoid hyperplasia without otitis media (AH) presenting either with snoring or
      upper respiratory tract infections. B lymphocytes comprised on average 64, 66 and
      58% of all mononuclear cells in the respective patient groups. The majority of
      the B lymphocytes were of the follicular mantle zone phenotype expressing surface
      IgD (on average 69, 67 and 70% of all B lymphocytes in the respective patient
      groups). Almost one third of the B lymphocytes were of the germinal center cell
      phenotype, expressing CD38 but negative for surface IgD (on average 29, 30 and
      25% in the respective patient groups). CD3+ T lymphocytes comprised 33, 33 and
      40%, respectively, of all mononuclear cells, and the average CD4+/CD8+ ratio was
      5.2, 4.9 and 5.7, respectively. No statistically significant differences between
      the patient groups were seen in these T- and B-lymphocyte subpopulations. These
      results suggest that the relative sizes of the germinal center, follicular mantle
      and interfollicular compartments of the adenoids do not correlate with the
      disease status of the middle ear cavity.

PMID- 8980620
TI  - Immunohistochemistry (Ki-67 and p53) as a tool in determining malignancy in
      smooth muscle neoplasms (exemplified by a myxoid leiomyosarcoma of the uterus).
AB  - Smooth muscle tumours of the uterus at times represent a problem as it may be
      difficult to distinguish between benign and malignant tumours. The myxoid
      leiomyosarcoma (a rare type of neoplasm) reported here is an example of this. We
      present a case history and examine the suitability of Ki-67 and p53 as indicators
      of malignancy. The two antibodies were tested on seven leiomyomas, three atypical
      (borderline) leiomyomas, seven leiomyosarcomas and the myxoid leiomyosarcoma
      using microwave oven antigen retrieval. The leiomyomas had the lowest and the
      leiomyosarcomas the highest proliferation rate. The leiomyomas had no expression
      of p53, the atypical leiomyomas had a few scattered positive nuclei, and 5/7 of
      the leiomyosarcomas had overexpression of p53. The myxoid leiomyosarcoma had a
      positive reaction for p53 in clusters. The results suggest that Ki-67 and p53
      might be useful as indicators of malignancy.

PMID- 8980621
TI  - Local and systemic antibody levels against protein D of Haemophilus influenzae
      following immunization and infection in rats.
AB  - Outer membrane proteins of Haemophilus influenzae are considered as possible
      vaccine candidates against non-typable H. influenzae (NTHi), a major cause of
      respiratory infections. Here, we study local and systemic antibody responses to
      protein D, a well-conserved 42-kDa membrane protein, following local and systemic
      immunization, and experimental acute otitis media (AOM) with NTHi and H.
      influenzae type b (Hib) in rats. Animals that were challenged and rechallenged in
      the middle ear with Hib strain Minn A or NTHi strain 1161 developed IgG and IgA
      antibodies in serum but not in middle ear lavage (MEL) material or saliva. In
      contrast, following per oral immunization with NTHi strain 772 and Escherichia
      coli JM83 (pHIC348) (containing protein D gene) and, to a lesser degree after
      intranasal inoculation of NTHi strain 772, high saliva IgA antibodies to protein
      D developed, but there was no rise in antibodies to protein D in the MEL material
      or the sera of these animals. These results show that protein D can elicit
      different systemic and local antibody responses depending on the site of delivery
      and the form of administration. Furthermore, experimental AOM with NTHi and Hib
      induces systemic IgG and IgA antibodies to protein D but fails to induce a
      mucosal immune response.

PMID- 8980622
TI  - Effect of insulin and epidermal growth factors on the synthesis of
      glycosaminoglycans/proteoglycans in cultured human malignant mesothelioma cells
      of different phenotypic morphology.
AB  - Two human malignant mesothelioma cell sublines, one with a fibroblast-like and
      the other with an epithelial differentiation, were examined for their capacity to
      synthesize glycosaminoglycans in the presence of IGF-I, EGF, and their
      combination. This synthesis depends on the morphology of the mesothelioma cells,
      with many-fold higher amounts of both hyaluronan and proteoglycans being produced
      by the cells with epithelial morphology than by those of the fibroblast
      phenotype. In both cell lines this synthesis was affected in a dose-dependent
      fashion by the exogenously added growth factors and exposure to IGF-I and EGF in
      combination showed a synergistic effect. This effect of those factors seems to be
      mediated via protein tyrosin kinase-dependent receptors and was different in the
      fibroblast-like and epithelial cells. The synthetic rates of the various
      glycosaminoglycans formed (hyaluronan, galactosaminoglycans and heparan sulfate)
      were also variously affected by these factors, indicating differences in how the
      synthesis of the various glycosaminoglycans is regulated. The results obtained
      suggest a close correlation between the presence of the appropriate growth
      factor(s), the process of cell differentiation and the synthesis of
      glycosaminoglycans in these cells.

PMID- 8980623
TI  - High incidence and aggressive growth of non-AIDS-defining cancers among AIDS
      patients in Oslo.
AB  - The spectrum of cancers advanced by AIDS is disputed. To supplement the register
      based investigations, we have studied the occurrence of non-AIDS-defining
      malignancies in a closely followed population of AIDS patients. The population
      comprises 255 patients fulfilling CDC's clinical AIDS definition, representing
      91% of all adult AIDS patients from Oslo 1983-1995. Full autopsy was performed on
      73% of the 211 fatal cases. Adding patients with CD4 cell counts below 200
      cells/mm3 to match the US AIDS definition, the population increases to 344,
      including 225 deceased. The expected number of cancer cases was calculated from
      age- and sex-specific cancer incidence rates for Oslo 1988-1992. The number of
      non-AIDS-defining cancers was six (clinical CDC criteria) or eight (US AIDS
      definition), compared to expected numbers of 0.54 and 1.0, respectively. At
      autopsy, four of eight cases showed extensive tumor dissemination with
      involvement of the heart. These observations suggest that (at least some) non
      AIDS-defining cancers occur at increased rates and show aggressive growth pattern
      in AIDS.

PMID- 8980624
TI  - Antibody reactivities to glutamate-rich peptides of Plasmodium falciparum
      parasites in humans from areas of different malaria endemicity.
AB  - Synthetic P. falciparum peptides were evaluated as tools in epidemiological
      investigations of malaria. Plasma IgM and IgG antibody reactivities against
      synthetic peptides covering sequences of glutamate-rich protein (GLURP) and
      acidic-basic repeat antigen (ABRA) were measured by ELISA in individuals from
      malaria-endemic areas of Sudan, Indonesia and The Gambia to study antibody
      responses to these peptides in donors living in areas of different malaria
      endemicity. IgG and IgM reactivities to the peptides increased with malaria
      endemicity, although there were no differences in reactivities to the GLURP
      peptide between non-exposed donors and donors living in areas of low malaria
      endemicity. IgG reactivities to the GLURP peptide in Sudanese adults were high
      one month after treatment in all adults tested, while IgG reactivities to the
      ABRA peptide were infrequent. IgM responses to the peptides tested were
      shortlived in most patients. In Gambian children with malaria, IgM reactivities
      but not IgG antibody reactivities against the ABRA peptide were higher in those
      with mild malaria than in those with severe malaria. The peptides may be useful
      in future epidemiological studies, especially in areas of low malaria endemicity.

PMID- 8980625
TI  - Histo-blood group antigens in human fetal thymus and in thymomas.
AB  - The glycosylation of epithelial cell surface antigens follows cellular
      differentiation, and changes in the pattern of expression are seen in various
      premalignant and malignant epithelial lesions. The distribution of type-2 chain
      ABH-carbohydrate structures (N-acetyl-lactosamine, H-type 2 chain, Le-y, Le-x and
      sialyl-Le-x) of the ABO-histo-blood group system was investigated in 19 normal
      fetal thymuses (gestational age 16 to 39 weeks) and in 19 thymomas in order to
      study possible tumor-associated changes in the glycosylation pattern. The
      material was investigated by immunochemical stainings of formalin-fixed paraffin
      imbedded tissue using monoclonal antibodies with defined specificity. In fetal
      thymus the epithelial cells of the medulla and the Hassal's bodies strongly
      expressed elongated carbohydrate structures (Le-y, Le-x and sialyl-Le-x). In a
      few cases the cortical epithelial cells weakly expressed Le-x and sialyl-Le-x.
      Compared with fetal thymus 16 of the thymomas showed a total loss, or a very much
      reduced expression of elongated carbohydrate structures. Three thymomas, which
      histologically had been reclassified according to Kirchner & Muller-Hermelink
      (14) as high grade thymic carcinomas, revealed strong expression of Le-y,
      moderate expression of Le-x and weak expression of sialyl-Le-x. This is of
      interest as in other tumors Le-y is correlated with increased cell motility and
      with poor prognosis.

PMID- 8980626
TI  - Immunity to experimental Salmonella typhimurium infections in rats. Transfer of
      immunity with primed CD45RC+ and CD45RC- CD4 T-cell subpopulations.
AB  - The protective effect of primed CD4 T cells against a lethal dose of Salmonella
      typhimurium was studied in Lewis rats. Primed CD4 T cells were obtained by
      inoculating Lewis rats with a non-lethal dose of S. typhimurium. Four weeks after
      the infection, spleen CD4 T cells were separated by antibody-coated magnetic
      microspheres using an antibody against the CD4 molecule (W3/25). The cells were
      separated according to their expression of the CD45RC isoform of the leukocyte
      common antigen by FACS. CD45RC+ and CD45RC- CD4 T-cell subpopulations were
      transferred to untreated rats 24 h prior to infection with S. typhimurium.
      Transfer of CD45RC+ and CD45RC- CD4 T cells induced a significant survival, p =
      0.022 and p = 0.023 respectively, following inoculation with S. typhimurium
      compared to animals with no cells transferred. The infection induced an increase
      in CD4 T cells expressing the CD45RC isoform compared to untreated controls (p <
      0.001). It is concluded that both CD45RC+ and CD45RC- cells can induce a
      significant protection against S. typhimurium infections in rats. Therefore the
      CD45RC antigen cannot be used as a phenotypic marker for functionally distinct
      CD4 T-cell subpopulations. The infection-induced increase in CD45RC+ cells is
      most likely due to generation of antigen-specific memory T cells.

PMID- 8980627
TI  - Microbiologically verified diagnosis of infectious spondylitis using CT-guided
      fine needle biopsy.
AB  - Using a computed tomography (CT)-guided technique we have been able to obtain
      fine needle spine biopsies directly from an affected vertebra or disk plate in 14
      patients suspected of infectious spondylitis. The bioptic material was cultivated
      immediately and incubated for 14 days. Cultures from eight patients were
      positive. No single microbiological agent was predominant though coagulase
      negative staphylococci were frequent. In no case were mycobacteria found. Bioptic
      material from six patients did not give rise to growth of microorganisms. We were
      able to successfully treat the eight patients with a culture-positive biopsy. We
      think that biopsies are crucial for establishing a microbiological diagnosis. The
      whole procedure takes less than one hour; it is performed under local anaesthesia
      and is thus not very stressful for the patient: The success rate for obtaining a
      positive spine biopsy was 57%.

PMID- 8980628
TI  - Aminoglycoside resistance mechanisms in Enterobacteriaceae and Pseudomonas spp.
      from two Danish hospitals: correlation with type of aminoglycoside used.
AB  - Sixty-two aminoglycoside-resistant Gram-negative enteric bacteria were isolated
      over a 3-year period from two hospitals (Bispebjerg and Esbjerg) among a total of
      almost 270,000 isolates. These hospitals were selected because of their different
      aminoglycoside policies during the years investigated. At Bispebjerg Hospital the
      principal aminoglycoside used was tobramycin, while gentamicin was the first
      choice at Esbjerg Hospital. Escherichia coli was the most frequently found
      aminoglycoside-resistant species. Among the 61 aminoglycoside-resistant strains
      studied, resistance was due to aminoglycoside-modifying enzymes in all except two
      Xanthomonas maltophilia strains. The ANT(2") enzyme occurred significantly more
      often at Esbjerg Hospital (p = 0.001), while enzymes of the AAC(3) or AAC(6')
      moieties were more common, but not significantly so, at Bispebjerg Hospital. The
      phenotypic pattern of aminoglycoside resistance, as determined by disc diffusion,
      correlated 100% with the ANT(2") and AAC(3)-V (the two most common enzymes among
      the isolates) genotype of the organisms as established using DNA probes. Median
      minimum inhibitory concentrations (MICs) (mg/l) for clinically utilized
      aminoglycosides were: amikacin (1.6), gentamicin (25.0), kanamycin (50.0),
      netilmicin (1.6-25.0) and tobramycin (12.5-50.0). Isolates from Bispebjerg
      Hospital revealed significantly higher MICs for netilmicin and tobramycin (p <
      0.01) as compared to isolates from Esbjerg Hospital.

PMID- 8980629
TI  - Cloning and sequencing of a cluster of genes encoding novel enzymes of trehalose
      biosynthesis from thermophilic archaebacterium Sulfolobus acidocaldarius.
AB  - Trehalose biosynthesis genes, treZ, treX and treY, encoding
      maltooligosyltrehalose trehalohydrolase (TreZ), glycogen debranching enzyme
      (TreX), and maltooligosyltrehalose synthase (TreY) have been cloned from the
      thermophilic archaebacterium Sulfolobus acidocaldarius ATCC33909. The amino-acid
      sequences deduced from treZ, treX and treY are composed of 556, 713 and 720 amino
      acid residues, respectively. TreZ and TreY are 33-40% homologous to the
      corresponding enzymes from Arthrobacter sp. Q36. We have proposed that the
      biosynthesis of trehalose in Sulfolobus occurs via the actions of the three
      enzymes encoded by treZXY.

PMID- 8980631
TI  - Natural and synthetic betaines counter the effects of high NaCl and urea
      concentrations.
AB  - Escherichia coli was used as a model system to evaluate a range of betaines for
      their ability to protect against salt and urea stresses. Betaine structure
      determined the salt and urea protective effects. Dimethylthetin conferred salt
      protection similar to glycine betaine, whereas dimethylsulfoniopropionate (DMSP)
      was less effective than either glycine betaine or dimethylthetin, but similar to
      propionobetaine (its nitrogen analogue). Hydrophobic alpha-substituents altered
      salt tolerance. Valine betaine with an aliphatic side group conferred salt
      tolerance similar to glycine betaine. Betaines containing phenyl groups
      (phenylglycine, phenylalanine and N-phenylglycine betaines) did not confer salt
      protection, growth being similar to, or less than the control (no betaine).
      Hydrophobic groups decreased the ability to protect against urea stresses; valine
      betaine conferred poor urea tolerance. The addition of an hydroxyl group
      increased the ability of a betaine to protect against urea denaturation. Proline
      betaine, an effective salt protector, conferred poor urea tolerance. Increasing
      the charge separation in the betaine molecule decreased the ability to confer
      urea tolerance. Thiolanium, pyridinium and triethylglycine betaines, with larger
      cationic functions, conferred no urea tolerance to E. coli.

PMID- 8980630
TI  - Purification and characterization of a 4-hydroxynonenal metabolizing glutathione
      S-transferase isozyme from bovine pulmonary microvessel endothelial cells.
AB  - Previous studies have suggested that a group of structurally and immunologically
      related mammalian glutathione S-transferases (GSTs) which utilize 4
      hydroxynonenal (4-HNE) as the preferred substrate and show glutathione peroxidase
      activity towards phospholipid hydroperoxides may be important for the defense of
      cells against lipid peroxidation. In present studies we have purified and
      characterized GST isozymes of bovine pulmonary microvessel endothelial (BPMVE)
      cells. The results of these studies indicate that BPMVE cells express relatively
      high amounts of a GST isozyme which utilizes 4-HNE as the preferred substrate.
      This GST isozyme purified to homogeneity from BPMVE cells showed remarkably high
      specific activity towards 4-HNE (48.3 units/mg protein) and had similar
      immunological, kinetic, and structural characteristics as reported for mouse
      enzyme mGSTA4-4 and other mammalian GSTs of this group. Since the endothelial
      cells are exposed to constant oxidative stress, we suggest that this GST isozyme
      may be important for the defense of these cells against lipid peroxidation.

PMID- 8980632
TI  - Dimerization of an antigenic peptide leads to strong interaction with its
      antibody.
AB  - A sequential epitope reacting with a monoclonal antibody against Panulirus
      interruptus hemocyanin was localized in the C-terminal CNBr peptide. As the
      antibody reacted with about equal affinity with different subunits of this and
      with hemocyanin from another spiny lobster, Palinurus vulgaris, the epitope was
      assigned to a conserved sequence region. The CNBr peptide, which was linked to
      another peptide via a disulfide bridge, was reduced and reoxidized. As a result,
      not the heterodimer but only the two disulfide-linked homodimers were formed. The
      dimeric C-terminal peptide had a much higher affinity for the monoclonal antibody
      than the monomeric peptide. This may be explained by the presence of two
      independent mobile interaction sites in each of the two reacting molecules.

PMID- 8980633
TI  - Characterization of trehalase activities from the thermophilic fungus Scytalidium
      thermophilum.
AB  - The thermophilic fungus Scytalidium thermophilum produced large amounts of
      intracellular and extracellular trehalase activity when grown on starch as the
      sole carbon source. The specific activity of the purified proteins: 1700 U (mg
      protein)-1 (extracellular) and 3700 U (mg protein)-1 (intracellular), was many
      times higher than the values reported for other microbial sources. The apparent
      molecular mass of the native enzymes was estimated to be 370 kDa (extracellular
      trehalase) and 398 kDa (intracellular trehalase) by gel-filtration
      chromatography. Analysis by SDS-PAGE showed unique polypeptide bands of approx.
      82 kDa (extracellular trehalase) and 85 kDa (intracellular trehalase), suggesting
      that the native enzymes were composed of five subunits. The carbohydrate content
      of extracellular and intracellular trehalases was estimated to be 81% and 51%,
      respectively. Electrofocusing indicated a pI of 3.7 and 3.4, respectively, for
      the extracellular and intracellular enzymes. Both trehalases were highly specific
      for trehalose and were stimulated by calcium and manganese. Calcium and manganese
      also protected both trehalases from thermoinactivation. Inhibition was observed
      in the presence of aluminium, mercurium, copper, zinc, EDTA, ADP, and ATP.
      Apparent Km values, for the extracellular and intracellular trehalases, were 3.58
      mM and 2.24 mM, respectively. The optimum of pH for the extracellular and the
      intracellular trehalase was 6.0, and the optimum of temperature 60 degrees C and
      65 degrees C, respectively.

PMID- 8980634
TI  - The retention mechanism of cell wall proteins in Saccharomyces cerevisiae. Wall
      bound Cwp2p is beta-1,6-glucosylated.
AB  - It has been proposed that the cell wall proteins of Saccharomyces cerevisiae are
      anchored by means of a beta-1,6-glucose-containing side chain. Recently, we have
      identified three cell wall mannoproteins. Two of these mannoproteins are
      recognized in their cell wall bound form by an antiserum raised against beta-1,6
      glucan but the third, Cwp2p, is not. This could indicate the existence of
      alternative retention mechanisms for cell wall proteins. Western analysis of a
      fusion protein consisting of Cwp2p and the reporter enzyme alpha-galactosidase
      revealed that this protein is glycosyl phosphatidylinositol-anchored in the
      intracellular precursor form and is recognized by an anti beta-1,6-glucan
      antiserum in the cell wall bound form. The cell wall bound forms of fusion
      proteins consisting of the anchor regions of Sed1p or Flo1p and alpha
      galactosidase were also recognized by an anti beta-1,6-glucan antiserum. This is
      consistent with the existence of a general anchoring mechanism of proteins to the
      cell wall by means of a beta-1,6-glucose-containing carbohydrate chain. Western
      analysis of a yeast strain producing c-myc epitope tagged Cwp2p revealed that
      this protein is only detectable if fatty acid chains are present on the protein,
      indicating that the lack of recognition of Cwp2p by an anti beta-1,6-glucan
      antiserum is caused by a blotting artefact of the mature protein.

PMID- 8980635
TI  - Motions of tryptophan residues in asialylated human alpha 1-acid glycoprotein.
AB  - The fluorescence of the tryptophan residues of asialylated human alpha 1-acid
      glycoprotein (orosomucoid) was investigated. Red excitation spectra did not lead
      to a shift of the fluorescence emission maximum of the fluorophore, i.e., motions
      of the Trp residues depend on their microenvironment. This result was confirmed
      by anisotropy studies as a function of temperature in the range of 7 to 35
      degrees C (Perrin plot). In order to determine the frictional resistance to the
      local rotations of the tryptophan residues the protein was dissolved in a mixture
      of 80% glycerol buffer, and the fluorescence anisotropy was measured in the
      temperature range of -45 to + 20 degrees C. The Y-plot analysis of the anisotropy
      indicated that the mean motion of the two Trp residues buried in the protein core
      was different from that of the Trp residue of the surface. The average angles of
      rotations for buried and surface residues were 10 and 14 degrees C of arc,
      respectively.

PMID- 8980636
TI  - The chloroplast envelope is permeable for maltose but not for maltodextrins.
AB  - Permeation of [14 C]maltose into the stroma (measured as the sorbitol-impermeable
      space) of isolated intact spinach (Spinacia oleracea L.) chloroplasts was studied
      using the silicone oil centrifugation technique. Maltose uptake showed Michaelis
      Menten-kinetics with a K(m) of 25 mM and a Vmax of 19.5 mumol maltose. mg Chl-1.
      h-1 at 15 degrees C. Lack of interaction of glucose and maltose uptake suggested
      the presence of individual translocators for maltose and glucose in the inner
      chloroplast envelope. Maltose uptake was markedly inhibited by maltodextrins
      (maltotriose up to maltoheptaose). The corresponding [14C]maltodextrins were
      prepared by degradation of [14C]starch with pullulanase and alpha-amylase and
      purified by high performance TLC. None of these maltodextrins, when administered
      at a concentration of 10 mM, was transported into the sorbitol-impermeable space
      of the chloroplasts. The results suggest that the transport system for maltose is
      also accessible to maltodextrins but that only maltose can be translocated across
      the inner envelope of spinach chloroplasts.

PMID- 8980637
TI  - Multiple retinoids alter liver bile salt-independent retinyl ester-hydrolase
      activity, serum vitamin A and serum retinol-binding protein of rats.
AB  - Liver bile salt-independent retinyl ester hydrolase (BSI-REH) has been suggested
      to play a significant role in the hydrolysis of chylomicron derived retinyl
      esters. Studies were conducted to investigate the individual effects of N-(4
      hydroxyphenyl)retinamide (HPR), retinoic acid, 13-cis-retinoic acid, Acitretin
      and Temarotene on BSI-REH, serum retinol, and serum retinol-binding protein (RBP)
      concentrations. We have demonstrated that micromolar concentrations of HPR,
      retinoic acid, 13-cis-retinoic acid or Acitretin significantly reduced the in
      vitro hydrolysis of retinyl palmitate. In contrast, Temarotene stimulated retinyl
      palmitate hydrolysis by BSI-REH. Retinoic acid and 13-cis-retinoic acid produced
      transient, but significant, depressions of both serum retinol and RBP
      concentrations, when the individual retinoids were administered orally to rats.
      The duration of the depression was shorter than we previously observed with acute
      HPR administration. Furthermore, Acitretin appeared to function with bimodal
      activity, producing significant depression of serum retinol at 2 h and 24 h. No
      effect of Acitretin or Temarotene on serum RBP concentration was observed. The
      alterations observed in BSI-REH activity, serum retinol and RBP concentrations
      provide evidence that these retinoids can alter liver retinyl ester hydrolysis,
      but the effects observed on serum retinol concentration can only be partially
      explained by the BSI-REH activity.

PMID- 8980638
TI  - Comparative studies of the fate of free and liposome-entrapped hydroxypropyl-beta
      cyclodextrin/drug complexes after intravenous injection into rats: implications
      in drug delivery.
AB  - Inclusion complexes of 14C-labelled hydroxypropyl-beta-cyclodextrin (HP beta-CD)
      with tritiated dehydroepiandrosterone (DHEA), retinol (RET) and dexamethasone
      (DEX) were entrapped in the aqueous phase of liposomes composed of distearoyl
      phosphatidylcholine. Incubation of liposome-entrapped complexes in the presence
      of rat blood plasma at 37 degrees C resulted in complex dissociation and drug
      leakage in the media at a rate which was minimal for DEX/HP beta-CD (11%), modest
      for RET/HP beta-CD (23%) and considerable for DHEA/HP beta-CD (56%; 60 min). In
      contrast, the HP beta-CD moiety of the complexes was retained by liposomes
      quantitatively. Free complexes injected intravenously into rats were cleared
      rapidly from the circulation with most (up to 94%) of the HP beta-CD moiety
      recovered in 24 urine together with lesser and variable amounts of drug (up to
      46% of the dose) in a pattern (DHEA < RET < DEX) that was consistent with the
      extent of drug association with HP beta-CD in the presence of plasma. A
      significant proportion of the drugs (up to 25% of the dose)(but very little HP
      beta-CD) was removed by the liver where drugs were catabolised rapidly, probably
      following complex dissociation and transport to the tissue via plasma proteins.
      Injection of entrapped complexes revealed that liposomes alter their
      pharmacokinetics with only 6-13% of HP beta-CD and a moderate proportion of drugs
      (up to 26% of the dose) recovered in the urine. Much of the HP beta-CD moiety of
      the liposomal complexes was recovered in the liver (up to 83%) and spleen (up to
      13% of the dose) by 30 min after injection, together with a variable proportion
      of drugs in a pattern (DHEA < RET < DEX) which reflected that of complex
      dissociation in vitro. Longer term experiments where animals injected with
      liposome-entrapped complexes were killed at time intervals (up to 24 days),
      revealed that HP beta-CD is eliminated from the tissues, albeit at a very slow
      rate. Moreover, the metabolism of individual drugs in the tissues following
      vesicle disintegration, appeared to depend on the rate of complex dissociation
      with DEX, for instance, reaching values of 4-6% (liver) only after 14 days. It is
      concluded that administration of drug/cyclodextrin inclusion complexes via
      liposomes could serve as a means to control the action of a wide range of
      therapeutic agents.

PMID- 8980639
TI  - Effect of in vivo iron supplementation on oxygen radical production by soybean
      roots.
AB  - Both total iron content and the in vitro rate of iron reduction were higher in
      roots grown in the presence of exogenously added iron (up to 500 microM) than in
      roots grown in absence of supplemented iron. In vivo generation of reactive O2
      species by intact roots was assessed employing 2',7'-dichlorofluorescein
      diacetate oxidation to a fluorescent product. Roots developed in the presence of
      500 microM Fe-EDTA, showed significantly increased fluorescence (64%), as
      compared to roots developed in absence of added iron, suggesting that iron
      supplementation led to oxidative stress in vivo. At the subcellular level, iron
      content and Fe-EDTA reduction rate were significantly increased in microsomes
      isolated from roots developed in the presence of exogenously added iron, as
      compared to microsomes from roots grown in the absence of iron. Microsomes from
      Fe supplemented plants exhibited a 51% increase in 2',7'-dichlorofluorescein
      diacetate oxidation rate, a 55% increase in superoxide anion generation, and a
      four-fold increase in hydroxyl radical production as compared to controls. Iron
      supplementation did not affect the activity of antioxidant enzymes or the content
      of total thiols, however alpha-tocopherol content was significantly decreased in
      the homogenates and the microsomes isolated from roots supplemented with iron, as
      compared with values in roots developed in absence of iron. These data suggest
      that in vivo iron supplementation increased oxygen radical generation.

PMID- 8980640
TI  - Sequence analysis of an operon of a NAD(P)-reducing nickel hydrogenase from the
      cyanobacterium Synechocystis sp. PCC 6803 gives additional evidence for direct
      coupling of the enzyme to NAD(P)H-dehydrogenase (complex I).
AB  - The sequence of a NAD(P)-reducing hydrogenase operon of Synechocystis sp. PCC
      6803 containing genes for a small and a large hydrogenase subunit and six
      additional ORFs was determined. Until now only 11 of the 14 polypeptides of the
      NADH-dehydrogenase of E. coli were found in Synechocystis. By sequence homologies
      we suggest that the missing subunits of the peripheral part of the dehydrogenase,
      containing most of the FeS-clusters, are encoded by three ORFs of this operon.
      This hypothesis is discussed in relation to the NAD(P)-reducing hydrogenase of
      Synechocystis.

PMID- 8980641
TI  - Spectroscopic studies of the met form of the extracellular hemoglobin from
      Glossoscolex paulistus.
AB  - Sephadex G-200 chromatography of the extracellular hemoglobin from the giant
      earthworm G. paulistus in the met form presents a single peak at pH 7.0 and two
      peaks at pH 9.0 as a result of alkaline dissociation. SDS-PAGE shows that the
      polypeptide chains are very similar to those observed for the oxy form and the
      two peaks at pH 9.0 correspond to the trimer contaminated by linkers and monomers
      which seems to be quite pure. The aquomet acid form is stable as an oligomer of
      molecular mass 3.1 x 10(6) Da only in a narrow pH range around neutrality.
      Increasing the pH above 7.5 leads to an irreversible transition from aquomet to
      hemichrome I which is the low-spin bis-imidazole complex. At pHs above 9.5-10.0 a
      second reversible transition takes place from hemichrome I to hemichrome II, a
      high-spin complex which is associated with the weakening and possible disruption
      of the proximal Fe--N histidine bond. Thus, increase in pH above 8.0 induces
      changes in the heme pocket that involve both the distal and proximal sides of the
      heme. EPR measurements show a very sharp decrease of the aquomet high-spin signal
      in the range of pH 7.0-8.0 and a very small low-spin signal even at liquid helium
      temperatures. The transition to hemichrome I is also accompanied by the loss of
      heme optical activity monitored by CD, which is consistent with the weakening of
      heme--globin interaction. Hemichrome I in the presence of cyanide gives the
      typical cyanometHb derivative which has a transition to a hemichrome at much
      higher pHs. This observation suggests that the dissociation of the oligomer in
      alkaline medium as well as the stability of the heme on the proximal side, depend
      both upon the ligand present at the sixth coordination position on the distal
      side. Hence, we believe that hemi(hemo)chrome formation in G. paulistus Hb and
      other invertebrate hemoglobins is a common phenomenon, not associated with
      protein denaturation, which may provide a fine tuning mechanism to control
      subunit interactions through changes in the distal side of the heme pocket.

PMID- 8980642
TI  - Inhibition of chicken liver carboxylesterase by activated carbonyls and carbonyl
      hydrates.
AB  - Identical Kcat values (approximately 40 s-1) are obtained for the chicken liver
      carboxylesterase catalyzed hydrolysis of phenyl, p-nitrophenyl and o-nitrophenyl
      benzoates providing support for the involvement of an acyl-enzyme pathway, with
      the rate-limiting deacylation of a common benzoyl-enzyme intermediate. Chicken
      liver carboxylesterase catalyzed fragmentation of (E)-benzilmonoxime O-2,4
      dinitrophenyl ether shows a pH dependence on a group active in the free base form
      with a pK'a approximately 5.0. The Ki-pH profile for benzil inhibition shows a
      dependence on a similar group with a pK'a = 5.4. The reactions between chicken
      liver carboxylesterase and the hydrated aldehyde, chloral hydrate, have shown
      this compound to be at once a substrate and potent inhibitor of the enzyme. The
      kinetics of inhibition are consistent with a mechanism in which the bound hydrate
      is first dehydrated in a rate-limiting step catalyzed by the enzyme. Nucleophilic
      attack by the active-site serine on the parent aldehyde produces a hemiacetal
      adduct. The Ki value for chloral hydrate inhibition calculated from the kinetic
      analysis (90 nM) compares favourably with the value measured from the steady
      state kinetics (87 nM).

PMID- 8980644
TI  - Peroxidatic degradation of azide by catalase and irreversible enzyme
      inactivation.
AB  - A study of the azide reaction with bovine liver catalase in presence of hydrogen
      peroxide has been performed, using conventional UV-visible spectrometry and
      activity measurements. Compound III and NO-ferrocatalase were the predominant
      forms of the enzyme observed in air and under nitrogen, respectively. A reaction
      scheme for peroxidatic degradation of azide by catalase is proposed. Accordingly,
      accumulation of Compound III is the main factor responsible for the reversible
      inhibition of 'catalatic' activity by azide, while formation of a complex between
      native catalase and azide has a negligible effect. Catalase is irreversibly
      inactivated by prolonged exposure to high levels of H2O2 and azide. The latter
      involves cleavage of the prosthetic group with liberation of the heme iron. Both
      in air and under nitrogen, generation of azidyl radicals seems to play a minor
      role in the irreversible inactivation process.

PMID- 8980643
TI  - New catalytic roles for serine esterases: a 19F-NMR study of the interaction of
      3,3,3-trifluoro-2,2-dihydroxy-1-phenyl-1-propanone with chicken liver
      carboxylesterase.
AB  - The reactions of 3,3,3-trifluoro-2,2-dihydroxy-1-phenyl-1-propanone (TDPP) with
      chicken liver carboxylesterase have shown that this ketone hydrate is not only a
      potent inhibitor of the enzyme, but also a substrate for a number of enzyme
      catalyzed reactions. The kinetics of inhibition are consistent with a mechanism
      in which the bound hydrate is initially dehydrated in a rate-limiting step
      catalyzed by the enzyme. Nucleophilic attack by the active-site serine on the
      parent ketone then produces a hemiketal adduct. However, the slow reactivation
      (by dialysis) of TDPP-inhibited enzyme indicates that the interaction with this
      inhibitor is more complex. At equilibrium, a dissociation constant of 2.4 pM was
      obtained for this interaction. 19F-NMR studies of the enzyme-TDPP complex show
      that after pre-equilibration, the major adduct is not the hemiketal adduct. It is
      proposed that this final adduct is a cross-linked adduct formed between TDPP, the
      active-site serine and the active-site histidine. 19F-NMR studies reveal that
      chicken liver carboxylesterase catalyses the cleavage of TDPP to yield either
      fluoride ion or trifluoroacetate, and also the benzilic acid rearrangement of
      TDPP to alpha-trifluoromethylmandelate. These products have also been identified
      in model studies of the reaction between TDPP and imidazole.

PMID- 8980645
TI  - GroEL reversibly binds to, and causes rapid inactivation of, human carbonic
      anhydrase II at high temperatures.
AB  - The initial yield of reactivation of GuHCl denatured human carbonic anhydrase II
      does not change with temperature between 3 and 35 degrees C. At temperatures
      above 35 degrees C, the enzymatic activity is not stable, but decreases over
      time. If the bacterial chaperonin GroEL is present during reactivation, the
      initial yield is lower compared to the spontaneous reaction at temperatures of 35
      50 degrees C. However, unlike the spontaneous reactivation, the enzymatic
      activity with time in the presence of GroEL. In the presence of GroEL, native HCA
      II incubated at elevated temperatures will rapidly loose enzymatic activity to
      the same value as during reactivation at that particular temperature; most of the
      activity will recover if the temperature is lowered when GroEL is present. It is
      evident that there is an equilibrium between an inactive intermediate of HCA II,
      probably bound to GroEL, and active enzyme. Furthermore, proline isomerization is
      part of the rate-limiting step of refolding even in the presence of GroEL, and it
      is very noteworthy that prolyl isomerase will influence the refolding of HCA II
      in the presence of GroEL.

PMID- 8980646
TI  - The inhibition of human factor Xa by plasminogen activator inhibitor type 1 in
      the presence of calcium ion, and its enhancement by heparin and vitronectin.
AB  - Plasminogen activator inhibitor type 1 (PAI-1), a member of serine proteinase
      inhibitor superfamily, is known to inhibit thrombin in the presence of either
      heparin or vitronectin. We analyzed possible inhibitory activity of PAI-1 on
      human factor Xa. PAI-1 inhibited factor Xa in the presence of calcium ion (Ca2+),
      whereas no inhibition was observed in the absence of Ca2+. Half maximal
      enhancement by Ca2+ was obtained at 0.8 mM. An equimolar complex formation
      between factor Xa and PAI-1 in the presence of Ca2+ was observed by SDS
      polyacrylamide gel electrophoresis. Both unfractionated heparin and vitronectin
      enhanced the inhibition only in the presence of Ca2+. Apparent second-order rate
      constant (ki) for the inhibition of factor Xa by PAI-1 at 5 mM Ca2+ was 1.6 x
      10(4) M-1 s-1, and was enhanced 3-fold by 2 u/ml of heparin (4.6 x 10(4) M-1 s-1)
      and 10-fold by 100 nM vitronectin (1.6 x 10(5) M-1 s-1), respectively. The
      interaction between Ca(2+)-bound factor Xa and PAI-1 could be important from the
      view of PAI-1 neutralization and enhancement of fibrinolysis.

PMID- 8980647
TI  - Substrate specificity of acetylxylan esterase from Schizophyllum commune: mode of
      action on acetylated carbohydrates.
AB  - Substrate specificity of a purified acetylxylan esterase from Schizophyllum
      commune was investigated on a variety of methyl per-O-acetyl glycopyranosides,
      methyl di-O-acetyl-beta-D-xylopyranosides and acetylated polysaccharides. The
      enzyme preferentially deacetylated the 3-position of methyl 2,3,4-tri-O-acetyl
      beta-D-xylopyranoside and 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranoside. Removal
      of the 3-acetyl group from the xylopyranoside was accompanied by a slower
      deacetylation at positions 2 and 4. A similarly slower, accompanying
      deacetylation occurred primarily at position 2 with the glucopyranoside. Such
      specificity corresponds well to the expected function of the esterase in
      acetylxylan degradation. Of the three possible diacetates of methyl beta-D
      xylopyranoside, the 3,4-diacetate was found to be the most rapidly deacetylated.
      Unexpectedly, products of its deacetylation were a mixture of 2- and 4
      monoacetate. The formation of the methyl 2-O-acetyl-beta-D-xylopyranoside
      involved an enzyme-mediated acetyl group transfer because the rate of the enzyme
      catalyzed reaction exceeded the rate of spontaneous migration of acetyl groups.
      This is the likely mechanism for acetyl removal from position 2 in the native
      substrate. The enzyme exhibited the highest regioselectivity with methyl 2,3,4,6
      tetra-O-acetyl-beta-D-mannopyranoside. An 80% conversion of this substrate to
      methyl 4,6-di-O-acetyl-beta-D-mannopyranoside, a new mannose derivative, was
      achieved. In contrast to the majority of lipases and esterases exploited for
      regioselective deacetylation, the S. commune acetylxylan esterase did not attack
      the C-6 acetyl linkages in methyl hexopyranosides when other acetyl groups were
      available.

PMID- 8980648
TI  - Purification and sequencing of napin-like protein small and large chains from
      Momordica charantia and Ricinus communis seeds and determination of sites
      phosphorylated by plant Ca(2+)-dependent protein kinase.
AB  - The basic protein fraction from seeds of castor bean (Ricinus communis L.)
      contains 4732 Da and 4603 Da proteins phosphorylated in vitro by plant Ca(2+)
      dependent protein kinase (CDPK). These proteins, RS1A and RS1B respectively, were
      purified by cation-exchange HPLC (SP5PW column) and reverse-phase HPLC (C18
      column) and identified as napin-like protein small chains by Edman sequencing and
      electrospray ionization mass spectrometry (ESMS). The other R. communis 4 kDa
      small chains (RS2A, RS2B, RS2C and RS2D) are not phosphorylated by CDPK and
      neither is the corresponding 7332 Da large chain (RL) that forms 1:1 disulfide
      linked complexes with RS2(A-D). RS1A/B is one of the best substrates found for
      plant CDPK (K(m) = 1.8 +/- 0.8 microM). RS2(A-D) (but not RL or RS1A/B) strongly
      inhibit calmodulin (CaM)-dependent myosin light chain protein kinase (MLCK) (IC50
      = 0.25 microM) and inhibit the Ca(2+)-dependent enhancement of dansyl-CaM
      fluorescence. The basic protein fraction from seeds of bitter melon (Momordica
      charantia) also contains napin-like proteins that are 1:1 disulfide-linked
      complexes of a small chain (MS1, MS2, MS3 or MS4) and a large chain (ML). The M.
      charantia small chains were purified and completely sequenced by Edman
      degradation and ESMS. M. charantia small chains MS1, MS2, and MS4 (but not MS3)
      are phosphorylated by CDPK to unit stoichiometry on S21 within the sequence
      R17SCES21FLR. The R. communis small chain RS1A is phosphorylated on S34 within
      the sequence R31QSS34SRR. Both of these phosphorylation site motifs are
      consistent with those found for other plant CDPK substrates.

PMID- 8980649
TI  - Reaction of E. coli catalase HPII with cyanide as ligand and as inhibitor.
AB  - Cyanide forms an inhibitory complex with the haem d-containing E. coli catalase
      HPII, spectrally similar to the cyanide complex of beef liver enzyme but with
      absorption bands shifted 90 nm towards the red end of the spectrum. Both the Kd
      and Ki values are approximately 7 microM in the wild-type enzyme. The cyanide
      reaction is slow, with a bimolecular 'on' constant approx. 2000 x smaller than
      that of eukaryotic enzyme, and an 'off' constant diminished by a similar amount.
      Catalases with a mutated distal histidine (H128) fail to bind cyanide at cyanide
      concentrations below 50 mM. Catalases with a mutated distal asparagine (N201)
      show only small changes in cyanide affinity from the wild type. The major
      fraction of HPII N201A has a Kd approximately 40 microM, and a minor fraction has
      a lower cyanide affinity; the major fraction of HPII N201Q has a Kd approximately
      15 microM. The Kd and Ki for HPII N201D is approximately 8 microM, essentially
      identical with that of the wild type but N201D appears to bind cyanide somewhat
      more rapidly than does wild-type enzyme. The HPII mutant N201H can be obtained in
      both haem d and protohaem forms; it exhibits two types of cyanide binding
      behaviour. In its protohaem form it binds cyanide poorly (Kd > or = 0.25 mM).
      After peroxide treatment converts t into haem d or a closely related species it
      binds cyanide with a much higher affinity (Kd approximately 15 microM). Cyanide
      binding to HPII requires a distal histidine to provide hydrogen-bonding
      stability, but not a distal asparagine. Rates of cyanide binding and release are
      controlled by haem group accessibility through the channel leading to the
      outside. In HPII N201H channel opening may depend upon oxidation of the haem from
      the starting protohaem to the final haem d form.

PMID- 8980650
TI  - Site-directed mutagenesis of the N-linked glycosylation site in platelet-derived
      growth factor B-chain results in diminished intracellular retention.
AB  - Pulse-chase analysis of human platelet-derived growth factor (PDGF) B-chain was
      conducted in stably transfected Chinese hamster ovary cells to determine
      precisely the kinetics of processing, intracellular trafficking and secretion.
      Newly synthesized 31 kDa monomers of the B-chain (p31) dimerized rapidly via
      disulfide bonds to a p54 species (t1/2 < 30 min). The p54 dimer was processed to
      a group of intracellular, cell surface (suramin-releasable) and secreted forms
      whose rates of appearance and disappearance from the cell were measured over a 48
      h period. The newly synthesized p31 species was quantitatively converted to p27
      by treatment with endoglycosidase H, consistent with efficient N-glycosylation at
      a site in the N-terminal propeptide region (Asn63-Met64-Thr65). Interruption of B
      chain glycosylation by oligodeoxynucleotide-directed mutagenesis resulted in a
      significant increase in suramin-releasable forms at the cell surface (p34-38) and
      a concomitant decrease in accumulation of an intracellular p24 species. The
      glycosylation-defective mutant exhibited slight increases in receptor binding and
      mitogenic activity. Our results suggest that N-linked glycosylation of the B
      chain is not important for formation of mitogenically active protein, but that it
      plays a role in early intracellular sorting and proteolytic processing events.

PMID- 8980651
TI  - Proton-NMR investigation of the heme cavity in the cyanomet derivative of the
      cooperative homodimeric hemoglobin from Scapharca inaequivalvis.
AB  - The active-site structure of the paramagnetic cyanomet complex of the cooperative
      homodimeric hemoglobin from Scapharca inaequivalvis has been investigated by
      solution homonuclear NMR. In spite of the large size (32 kDa), the residues on
      the key proximal F- and distal E-helices could be sequence-specifically assigned
      and placed in the heme pocket in a manner common to diamagnetic systems. These
      backbone assignments were greatly facilitated by the significant dispersion of
      backbone chemical shifts by the highly anisotropic paramagnetic susceptibility
      tensor of the low-spin ferric state. The remainder of the residues in contact
      with the heme are assigned based on unique contacts to the heme predicted by the
      crystal structure and the observations of scalar connectivities diagnostic for
      the residues. The magnitude of the dipolar shifts for non-ligated residues was
      used to determine the anisotropy and orientation of the paramagnetic
      susceptibility tensor, and the major axis found tilted from the normal in a
      manner similar to that found for the Fe-CO unit in the crystal structure. The
      combination of NOESY inter-residue and heme-residue contacts, paramagnetic
      induced relaxation and correlation between observed and dipolar shifts provide a
      description of the heme cavity in cyanomet Hb that is essentially the same as
      found in the carbonmonoxy Hb crystal structure. The pattern of both the heme
      methyl dominant contact shifts and the heme meso-proton dominant dipolar shifts
      are shown to be consistent with the orientation of the axial His. It is concluded
      that the present homonuclear NMR methods allow effective solution structure
      determination in the cyanomet form for dimeric Hb and suggest profitable
      extension to the tetrameric vertebrate hemoglobins.

PMID- 8980653
TI  - Study of the amidase signature group.
AB  - Computer methods for database search, multiple alignment and cluster analysis
      indicated significant homology between amino-acid sequences of 21 amidases or
      amidohydrolases (EC 3.5). All of them were found to be involved in the reduction
      of organic nitrogen compounds and ammonia production. A conserved motif was found
      which may be important in amide binding and in catalytic mechanisms. Homology
      studies between these amidases and some ureases, nitrilases and acyl-transferases
      or enzymes with unknown functions provided new insight into the evolution of
      these proteins. Dissemination of these genes seemed to be facilitated by transfer
      of genetic elements such as transposons and plasmids.

PMID- 8980652
TI  - Cleavage of caldesmon and calponin by calpain: substrate recognition is not
      dependent on calmodulin binding domains.
AB  - The calmodulin binding proteins, caldesmon and calponin, are cleaved by both
      major isoforms of calpain in vitro. The patterns of fragments generated by each
      enzyme are essentially identical for a given substrate. Qualitatively, the
      cleavage pattern of each substrate is unchanged by the presence or absence of
      calmodulin suggesting that the interaction between calmodulin and these
      calmodulin-binding proteins does not alter substrate recognition by calpain.
      However, calmodulin (at microM concentrations) does have a small, but
      significant, inhibitory effect directly on calpain as evidenced by slower rates
      of cleavage of alpha-casein, a protein that does not bind calmodulin. Inhibition
      is more pronounced with mu-calpain (15-25%) than with m-calpain (6-10%). In order
      to demonstrate, unequivocally, that substrate recognition does not require an
      interaction between calpain and a substrate's calmodulin-binding domain,
      recombinant, full-length caldesmon and a mutant lacking the calmodulin binding
      domain were tested as substrates for calpain in the presence and absence of
      calmodulin. Calpain produced similar cleavage patterns of the baculovirus
      expressed caldesmon and the truncated mutant. Competition experiments
      demonstrated that calpain does not discriminate between the truncated mutant and
      full length caldesmon. This suggests that substrate recognition by calpain was
      not altered significantly by the absence of the calmodulin-binding domain.
      Cleavage of a second calmodulin-binding protein, calponin was also examined. The
      rate of calponin cleavage was increased in the presence of calmodulin, an
      observation that is also inconsistent with any requirement for calpain to bind to
      its calmodulin-binding site. These results demonstrate that calmodulin-binding
      domains do not provide substrate recognition sites for calpains. It seems likely
      that the calmodulin-like regions of calpain function to bind calcium and to
      regulate enzyme conformation as required for activity and that they do not
      interact directly with most substrates.

PMID- 8980654
TI  - Mutational analysis of human uroporphyrinogen decarboxylase.
AB  - Uroporphyrinogen decarboxylase (URO-D), a heme biosynthetic enzyme, catalyzes the
      multi-step decarboxylation reaction converting uroporphyrinogen I or III to
      coproporphyrinogen I or III. The URO-D protein has been purified from several
      sources and its gene has been cloned from many organisms. In spite of this,
      little is known about the active site(s) of the enzyme. Inhibitor studies suggest
      that cysteine and histidine residues are important for enzyme activity. We
      employed the Kunkel method of site-directed mutagenesis to convert each of the
      six cysteines in human URO-D to serine and each of the three conserved histidines
      to asparagine. Recombinant mutant URO-D's were expressed in Escherichia coli,
      partially purified, and their kinetic properties compared to recombinant wild
      type URO-D. All cysteine mutants retained approx. 40% wild-type enzyme activity,
      indicating that no single cysteine is absolutely critical for the integrity of
      the catalytic site. The three histidine mutants also retained significant enzyme
      activity and one, (H339N), displayed unique properties. The H339N mutation
      resulted in an enzyme with high residual activity but decarboxylation of
      intermediate reaction products of the I isomer series was markedly abnormal. The
      histidine at residue 339 is likely important in imparting isomer specificity.

PMID- 8980655
TI  - Increased autocrine production of insulin-like growth factor II (IGF-II) alters
      serum sensitivity of MCF-7 human breast cancer cell proliferation.
AB  - Regulation of the growth of breast cancer cells is the result of a complex
      interaction between steroid hormones and growth factors, and in particular of
      oestrogen and insulin-like growth factors (IGF). Alteration of any one mitogenic
      component can affect the cell response to other pathways. Previous work has shown
      that increased autocrine production of IGF-II from a transfected inducible
      expression vector can result in reduced oestrogen sensitivity of growth of MCF-7
      human breast cancer cells. This report describes alterations to non-oestrogen
      regulated pathways of cell growth following enhanced IGF-II expression in these
      transfected MI7 cells. Serum sensitivity of cell growth in the absence of
      oestrogen was found to differ between MI7 and untransfected MCF-7 cells, in that
      growth of MI7 but not MCF-7 cells was strongly inhibited by high serum levels.
      Increased serum had no effect on levels of IGF-II mRNA, IGFIR, IGFBP4 mRNA, or
      IGFBP secreted in MI7 cells. However, growth inhibition by serum in MI7 cells
      could be overcome by increasing levels of IGF-II in the serum or by removal of
      IGFBP onto polycarbonate membranes. Thus, the growth inhibition by serum in MI7
      cells is concluded to result from the increased levels of IGFBP added with higher
      serum. This would support an inhibitory role for IGFBP on growth of breast cancer
      cells when cell growth is being driven by IGF pathways in the absence of
      oestrogen, and would suggest that cellular sensitivity to such factors can depend
      on levels of endogenous IGF production.

PMID- 8980656
TI  - Tissue kinetics in mouse tongue mucosa during daily fractionated radiotherapy.
AB  - The purpose of the present investigation was to quantify cell flux between the
      distinct layers of the epithelial lining of the ventral surface of mouse tongue
      during daily fractionated radiotherapy. A fraction of DNA-synthesizing cells in
      control epithelium, or at various days through a course of daily fractionated
      radiotherapy with 3 or 4 Gy per day, was labelled with [3H]dT or BrdUrd,
      respectively. The labelling indices (LI) in the different epithelial layers were
      defined histologically after autoradiography, or immunohistochemistry, at
      intervals between 1 and 10 days after label administration. In tongue epithelium
      of untreated mice, the minimum residence time of cells in the germinal layer is 2
      3 days. Migration through the functional layers requires an additional 2-3 days
      before labelled cells are observed in the most superficial layer of nucleated
      cells. A plateau in LI is observed for several days post-labelling in control
      epithelium, indicating an equilibrium between loss and proliferation of labelled
      cells. During fractionated radiotherapy, the minimum time from division to
      occurrence of labelled cells in the stratum lucidum is less than 2 days, and
      hence significantly shorter than in control epithelium. In contrast to untreated
      epithelium, no plateau in the germinal layer LI is seen, indicating that
      frequently both labelled daughters from dividing labelled cells are being lost
      from this compartment. In conclusion, the present data support a recently
      described model of radiation-induced accelerated repopulation in squamous
      epithelia, which postulates that the majority of damaged cells undergoes
      abortive' divisions resulting in two differentiating daughters.

PMID- 8980657
TI  - Region-specific DNA synthesis in brains of F344 rats following a six-day
      bromodeoxyuridine infusion.
AB  - Prolonged exposure to certain alkylating chemicals induces glial and meningeal
      tumours in rats, probably resulting from DNA damage to dividing neural cells. The
      present work evaluated DNA synthesis in the brains of untreated, young adult male
      F344 rats in order to define a BrdUrd infusion protocol to more adequately assess
      proliferation in slowly dividing neural cell populations. BrdUrd (2.5 to 160
      mg/ml) was administered for 6 days via subcutaneous osmotic pumps. Clinical
      toxicity was not observed at any dose. The labelling index (LI; % of cells per
      brain area that incorporated BrdUrd) and unit length labelling index (ULLI; % of
      cells per meningeal length that incorporated BrdUrd) were calculated for selected
      regions by counting labelled neural cells in defined areas of the right
      hemisphere in coronal brain sections. Intensely stained cells were numerous in
      the cerebral subependymal layer (LI = 35.8%); scattered in cerebral white matter
      tracts (e.g. corpus callosum and internal capsule; LI = 6.2%) as well as cerebral
      (ULLI = 4.2%) and cerebellar (ULLI = 3.6%) meninges; and rare in the hippocampus
      (LI > 0.1%). Mildy stained cells were dispersed in the pons (LI = 2.1%), deep
      cerebral (LI = 1.8%) and cerebellar (LI = 1.0%) grey matter, and thalamus (LI =
      0.3%). Phenotypically, BrdUrd-positive cells in neuropil were glial cell
      precursors and their progeny, while those associated with meninges were usually
      located in the superficial subarachnoid space and appeared to be fibrocytes.
      Using BrdUrd infusion, LI for glial precursors at these sites ranged from two- to
      10-fold higher than those reported previously after a brief parenteral pulse
      dose. These data indicate that continuous BrdUrd infusion for 6 days by
      subcutaneous osmotic pump is an efficient means of labelling neural cells
      throughout the brain.

PMID- 8980658
TI  - Differential effects of 2'-deoxyguanosine on peripheral blood mononuclear cell
      proliferation in healthy donors and Hashimoto's thyroiditis patients.
AB  - The aim of this study was to determine possible differences in peripheral blood
      mononuclear cells (PBMC) proliferation of healthy donors and Hashimoto's
      thyroiditis patients and whether a statistical approach to cell proliferation
      analysis might be used to discern the differences. The effect of a wide range of
      2'-deoxyguanosine (dGuo) concentrations (0-1250 microM) on the mitogen-induced
      proliferation of PBMC was studied in healthy donors and Hashimoto's thyroiditis
      patients. Activity levels of purine nucleoside phosphorylase (PNP) and adenosine
      deaminase (ADA) in PBMC were also measured. For the first time in a study of
      these models of dGuo toxicity in vitro, the analysis of polynomial trends of
      orders from 1 to 7 was applied to evaluate cell proliferation. A dose-dependent
      inhibition of mitogen-induced PBMC proliferation was observed in both groups.
      Data for linear trend established that PBMC from Hashimoto's thyroiditis patients
      were more sensitive to dGuo toxicity than PBMC from healthy donors. A positive
      quadratic trend at low dGuo doses was found in the cell proliferation of
      Hashimoto's thyroiditis patients. A decrease in PNP activity (P < 0.025) and an
      increase in ADA activity (P < 0.005) was observed in PBMC of Hashimoto's
      thyroiditis group. The differences in PBMC proliferation subjected to dGuo
      toxicity between the two groups could be related with the distinct pattern of
      purine salvage enzymes observed.

PMID- 8980659
TI  - Construction of a vector containing a site-specific DNA double-strand break with
      3'-phosphoglycolate termini and analysis of the products of end-joining in CV-1
      cells.
AB  - Previous studies have shown that linearized SV40-based shuttle vectors
      transfected into mammalian cells are efficiently recircularized by an error-prone
      end-joining pathway. To determine whether and with what specificity free radical
      mediated double-strand breaks are rejoined by this pathway, a structural mimic of
      such a break was introduced at a specific site in an SV40-based shuttle vector,
      by ligating purified 3'-phosphoglycolate-terminated oligonucleotides into 3'
      recessed ends generated in the linearized vector. These terminally blocked linear
      vectors were efficiently repaired and replicated when transfected into simian CV
      1 cells. Sequencing across the repair joints in progeny plasmid indicated that,
      for a blunt-ended vector, the most frequent mechanism of rejoining was splicing
      at a terminal 4-base homology; however, a significant fraction of the joints
      retained all bases from both ends of the break, consistent with a mechanism
      involving simple 3'-phosphoglycolate removal, followed by blunt-end ligation. For
      the analogous 3'-hydroxyl terminated break, the fraction of simple blunt-end
      ligations was considerably higher. For a phosphoglycolate-terminated vector with
      cohesive ends the most frequent repair mechanism was simple ligation of the
      annealed cohesive ends, presumably preceded by phosphoglycolate removal. For all
      these substrates, the remaining repair joints showed small or large deletions
      from one or both of the ends, usually with apparent annealing at short (1-4-base)
      homologies. The results suggest that while breaks with 3'-phosphoglycolates can
      be repaired, these blocked termini represent a significant barrier to DNA end
      joining, and can significantly alter its specificity. The presence of cohesive
      ends appears to improve markedly the fidelity of rejoining for terminally blocked
      double-strand breaks.

PMID- 8980660
TI  - Migration patterns in pulsed-field electrophoresis of DNA restriction fragments
      from log-phase mammalian cells after irradiation and incubation for repair.
AB  - An assay system was developed to detect changes of restriction fragment profiles
      obtained after pulsed-field gel electrophoresis (PFGE) for DNA from mammalian
      cells that were irradiated and incubated for repair. DNA was prepared from
      irradiated log-phase human melanoma cells (MRI 221) after incubation for repair
      (6 h) and was digested with the rare-cutting restriction enzyme NotI (RE) prior
      to PFGE separation. DNA-fragment size distributions were compared to the
      respective PFGE profiles from unirradiated controls. After doses of 5 and 10 Gy
      (plus a 6-h incubation for repair), the relative amount of DNA retained in the
      plug during PFGE was increased. For higher doses (30 and 60 Gy), this phenomenon
      was superimposed by the residual fragmentation (25-30% of the initial breakage of
      0.42 dsb/100 Mbp/Gy). Since irradiated cells accumulated in S phase during
      incubation for repair, a correction for the reduced electrophoretic migration of
      DNA from S-phase cells was necessary, and a 0.5% increase in DNA retention per 1%
      S-phase increment was found. However, the % retention for the 5 Gy plus repair
      sample was significantly higher than for the S-phase adjusted control (p < 0.01).
      Radiation induced DNA-protein crosslinks cannot account for the observed
      phenomenon because of the extensive proteolysis in DNA preparation, and also a
      loss of restriction enzyme recognition sites appear to be an unlikely explanation
      from simple quantitative considerations. Based on the recent observation of
      misrejoining during dsb repair, it is proposed that the incorrect joining of DNA
      ends also causes a more random distribution of replicating DNA in restriction
      fragments derived from cells in S phase after incubation for repair. This process
      would necessarily increase the proportion of DNA unable to migrate in PFGE.

PMID- 8980661
TI  - Biodosimetry after accidental radiation exposure by conventional chromosome
      analysis and FISH.
AB  - A 137Cs source was stolen from a radioactive waste depository in Estonia on 21
      October 1994 and kept in a private house for 4 weeks. This resulted in the death
      of one person, acute radiation injuries to four people and exposure of several
      other people to lower doses of radiation. Analysis of chromosomal aberrations in
      peripheral blood lymphocytes was used in the assessment of radiation exposure of
      18 people involved in the accident. Dose estimation assessment based on the
      frequencies of dicentric chromosomes was performed both by the standard method
      and by considering possible dose protraction and non-uniform exposure.
      Considerable differences in dose estimates were obtained depending on the
      approach used, ranging from about 1 Gy to almost 3 Gy in the patients most
      heavily exposed. In view of the deterministic health effects observed in some of
      the subjects, it was concluded that the dose estimates involving information on
      dose protraction were more realistic than those obtained by comparison with the
      standard high dose-rate calibration curve. Chromosome painting analyses using
      fluorescence in situ hybridization, with a probe cocktail for chromosomes 1, 2
      and 4 and centromere detection, were performed in parallel. Good agreement on
      dicentric chromosome frequencies was observed between the conventional and
      painting analyses. The frequencies of complete translocations were comparable
      with the frequencies of dicentric chromosomes. In addition to the complete
      translocations, a pronounced increase in the frequency of incomplete
      translocations was observed. Dose estimates performed on the basis of FISH
      translocation frequencies were consistent with the dicentric analysis.

PMID- 8980662
TI  - Quantification of FISH-painted chromosome aberrations after domestic radon
      exposure.
AB  - Chromosome painting (target chromosomes 1, 4, 12) was performed in peripheral
      lymphocytes from 25 occupants of nine houses with indoor radon concentrations of
      210-3000 Bqm-3. Compared to a control group, the mean frequency of symmetrical
      translocations of the radon group was slightly but not significantly (p < 0.10)
      increased. A similar tendency became apparent for a comparison of two groups of
      subjects with cumulative radon exposures above and below 2800 Bqm-3 y. It is
      concluded that FISH-based measurements of stable symmetrical translocations
      should reflect the cumulative radon exposure to haematopoietic compartments such
      as the red bone marrow rather than to mature blood lymphocytes. Since, however,
      radon-derived bone marrow doses are low and control frequencies of translocations
      are very high (about 10-fold higher than the value for conventionally scored
      dicentrics), the observed relative increase (1.5-fold) of the translocation
      frequency in blood lymphocytes is too small to discriminate chronic radon
      exposure from background.

PMID- 8980663
TI  - Comparison between fluorescence in situ hybridization and conventional
      cytogenetics for dicentric scoring: a first-step validation for the use of FISH
      in biological dosimetry.
AB  - In this study the suitability of fluorescence in situ hybridization (FISH) for
      dicentric detection using a commercially available alpha-satellite probe (Oncor)
      to label centromeres was compared with the conventional technique for the
      detection of unstable aberrations. A standard FISH protocol was applied for
      centromere labelling. Dose-response curves using blood samples irradiated in
      vitro with gamma-rays (60Co) at a dose-rate of 0.1 Gy/min were established using
      both techniques and compared. No statistical difference was observed between
      either method. The FISH technique thus allows a correct detection of unstable
      aberrations when an alpha-satellite DNA probe is used.

PMID- 8980664
TI  - Technical report: effect of cryopreservation on chromosomal aberration yield in
      irradiated lymphocytes.
AB  - Cryopreservation is the usual method to store cells before analysis or use, for
      instance for biological dosimetry purposes. Some investigations have shown that
      thawing following freezing may induce cell injury but few studies have been made
      of the effect of cryopreservation on cells containing radiation-induced unstable
      chromosomal aberrations. In this work, lymphocytes were irradiated with 1 to 4 Gy
      gamma rays and stored in liquid nitrogen. The dicentric and centric ring yields
      were analysed after storage periods of 1 week, 1 month and 3 months. No
      difference in aberration frequency from control, unfrozen samples was observed
      over this period. Lymphocytes stored at -196 degrees C for up to at least 3
      months may therefore be used for chromosome aberration scoring when over-exposure
      to ionizing radiation is suspected.

PMID- 8980665
TI  - P53 deficiency produces fewer regenerating spermatogenic tubules after
      irradiation.
AB  - The survival of clonogenic spermatogonia was assessed by scoring regenerating
      tubules at 35 days after irradiation, in the p53 null, heterozygote and wild-type
      mouse. Survival levels in the p53 null mouse after doses between 6 and 16 Gy were
      reduced by a factor of 3-4 compared with the levels in the heterozygote or wild
      type mouse, which responded similarly. However the radiosensitivity of the cells
      was similar in all three types of mice, and was characterised by a D0 = 1.7 Gy. A
      two-dose experimental protocol was used to show that the reduced level of
      survival in the null mouse at day 35 after irradiation was compatible with the
      interpretation that there were fewer functional radioresistant clonogenic
      spermatogonia in the testis of the unirradiated null mouse by about a factor of 3
      compared with that in the testis of the wild-type. The lower cell number was
      similar to the number deduced in other mice (BDF1), where the cells were much
      more resistant (D0 = 3.2 +/- 0.2 Gy). It is concluded that the lack of p53 causes
      a reduced level of tubule regeneration at 35 days after irradiation. This is
      probably not due to cellular radiosensitization, but possibly to a change in the
      stem cell cycle phase distribution resulting in a smaller proportion of resistant
      stem cells, which are assayed after high doses.

PMID- 8980666
TI  - Radiation-induced differentiation of human skin fibroblasts: relationship with
      cell survival and collagen production.
AB  - The aim of this study was to determine whether significant inter-individual
      differences exist between skin fibroblast strains obtained from radiotherapy
      patients in both radiation-induced differentiation and collagen production in
      vitro, for use as potential parameters for a predictive assay for fibrosis
      following radiotherapy in patients. Morphological cell differentiation was
      determined 7 days after irradiation in seven early-passage primary human
      fibroblast cell strains and correlated with cell survival. Collagen production
      was measured in two cell strains by flow cytometry and incorporation of 3H
      proline. There was a wide variation in the extent of radiation-induced
      differentiation for the seven cell strains, each showing a dose-related increase.
      The correlation between induced differentiation and cell survival was poor (r =
      0.64) but statistically significant (p < 0.01). Collagen synthesis increased 7
      days after irradiation for one cell strain (HF-48), as measured by incorporation
      of 3H-proline, but not in radiation sensitive AT-1 cells. The collagen I content
      of the two cell strains was assessed by flow cytometry but no significant
      differences were observed between the strains tested or with increasing dose. In
      conclusion, marked variations in radiation-induced fibroblast differentiation
      were observed between patients, this being an important criterion for a
      predictive assay.

PMID- 8980667
TI  - Chromatin structure and cellular radiosensitivity: a comparison of two human
      tumour cell lines.
AB  - The role of variation in susceptibility to DNA damage induction was studied as a
      determinant for cellular radiosensitivity. Comparison of the radiosensitive HX142
      and radioresistant RT112 cell lines previously revealed higher susceptibility to
      X-ray-induced DNA damage in the sensitive cell line using non-denaturing elution,
      but not when using alkaline unwinding. The present data also show that no
      difference in the amount of initial damage is seen when pulsed-field gel
      electrophoresis (PFGE) or comet analysis are used for DNA damage assessment.
      However, using the halo assay or a modified version of PFGE in which the higher
      DNA architecture remained partially intact, the radiosensitive cells showed
      steeper dose-response curves for initial DNA damage than the radioresistant
      cells. Analysis of the protein composition, of DNA-nucleoid structures revealed
      substantial differences when isolated from HX142 or RT112 cells. From our data,
      it is concluded that HX142 and RT112 differ in their structural organization of
      chromatin. As no differences in the kinetics of DNA damage rejoining were found,
      it is hypothesized that the same amount of lesions have a different impact in the
      two cell lines in that the 'presentation' of DNA damage alters the ratio of
      repairable to non-repairable DNA damage.

PMID- 8980668
TI  - Persistent increase in the rates of apoptosis and dicentric chromosomes in
      surviving V79 cells after X-irradiation.
AB  - In parallel to delayed reproductive death and delayed micronuclei in surviving
      V79 cells that have been reported, the frequency of apoptosis and dicentrics was
      investigated in the same cell line, 1-2 weeks after X-ray doses between 1 and 12
      Gy. Apoptosis was assessed by morphological criteria after staining with Giemsa
      and using the Apoptag method in parallel. The frequency of apoptosis peaked 48 h
      after irradiation at about 35% as a function of dose and then decreased to about
      10% on day 3. It remained 10 times higher than in unirradiated cells until day
      14. The frequency of dicentric chromosomes 24 h after irradiation increased
      according to a linear-quadratic function, up to about 110% after 12 Gy, decreased
      3 days later to about 10% and remained about 5-fold higher than in control cells.
      The dose-response relationship was similar for all the various end-points of
      expression of radiation induced genomic instability, showing a steep increase of
      the frequency with dose up to 3-4 Gy and with no further increase at higher
      radiation doses.

PMID- 8980669
TI  - Stimulatory effect of low dose X-irradiation on the expression of the human T
      lymphocyte CD2 surface antigen.
AB  - We investigated the early effects of low doses of ionizing radiation on the CD2
      gene expression in normal human T lymphocytes in order to clarify if low-dose
      ionizing radiation has an enhancing and/or stimulatory effect on the immune
      response. The results indicate that even low doses of X-irradiation strongly
      enhance the appearance of CD2 antigen, both in PHA-stimulated and in resting T
      lymphocytes as demonstrated by a rosette assay or by immunofluorescence.
      Moreover, an accumulation of CD2 mRNA is observed in X-irradiated cells compared
      with non-irradiated, a fact that is attributed mainly to transcriptional
      activation of the CD2 gene and not to stabilization of preformed mRNA.

PMID- 8980670
TI  - Hypoxic cell sensitization: low-dose intrinsic radiosensitivity is predictive for
      etanidazole efficacy in a panel of human tumour cell lines.
AB  - We used a cell sorter assay to evaluate the efficacy of the hypoxic cell
      sensitizer etanidazole over 3-4 logs of cell inactivation, with particular
      attention to the clinically relevant low-dose survival region. Analysis of the
      radiation responses in a panel of six human tumour cell lines under conditions of
      hypoxia and hypoxia with etanidazole revealed both a cell-line and radiation dose
      dependence in the sensitizing ability of this drug. Fits of the linear-quadratic
      (LQ) model to the low-dose region of cell survival indicate that sensitization of
      hypoxic cells by etanidazole results primarily from a modification of the beta
      parameter. This results in selective sensitization of cell lines in which this
      parameter contributes significantly to cell kill (i.e. a low alpha/beta ratio)
      and implies that the efficacy of this drug may be tumour specific. Selective
      modification of beta also leads to a radiation dose-dependence of the sensitizing
      enhancement ratio (SER). Analysis of the alpha and beta parameters derived from
      fist to data at low doses of radiation, suggests that the dose-dependence of this
      sensitizer, and possibly others including oxygen, is cell-line dependent; cell
      lines exhibiting a low alpha/beta ratio (i.e. with a large shoulder) exhibit
      little or no SER dose dependence, while those with a high alpha/beta ratio (i.e.
      small shoulder) exhibit a reduced SER at low doses as compared to high doses.
      Furthermore, this analysis suggests that modelling of the low-dose radiation
      survival data under conditions of hypoxia, can be predictive for both the
      absolute sensitizing ability of etanidazole, and its dose dependence. Our results
      also indicate that measurement of the in vitro low-dose radiation survival
      response in a panel of human cell lines is a more effective assay for evaluating
      agents like etanidazole than simply high-dose measurements in rodent cell lines
      which have, in general, demonstrated more congruent survival responses.

PMID- 8980671
TI  - Mechlorethamine-induced enhancement of radiation sensitivity of guanine.
AB  - This study describes and characterizes the interactions of nitrogen mustard
      mechlorethamine (HN2) with guanine and the radiation sensitivity of guanine in
      the presence of HN2. Briefly, in an equimolar solution (0.5 mmol dm-3) the pH
      dependence (pH 3.0-12.0) and time-dependence (0-36 h) of alkylation of guanine at
      room temperature were determined using a reverse-phase high-performance liquid
      chromatography (hplc) column. Based on the hplc peak areas of the product and
      intact guanine, the optimal pH for alkylation was determined to be 8.0.
      Similarly, the optimal time required for alkylation was 10 h. Two products, i.e.
      alkylated guanines, were detected (10:1, peak areas measured at 260 nm) and
      purified. Structural studies of the products were performed by direct insertion
      probe-electron impact mass spectrometry. These products were identified as N-(2
      chloroethyl)-N-[2-(7-guanyl)ethyl]-methylamine (product 2). At optimal
      conditions, samples of either guanine or an equimolar solution of guanine and HN2
      were 60Co irradiated (gamma-ray) at 25 Gy min-1 at doses up to 400 Gy. Both sets
      of samples were analysed by hplc. In each case, the sole radiation product
      observed and characterized was 8-hydroxy-guanine. Dose-yield plots were linear
      and showed that HN2 enhanced the radiation sensitivity of guanine. This increase
      in radiation sensitivity is attributed to the differences in electrophilic
      properties between nitrogen mustard and guanine.

PMID- 8980672
TI  - An interaction of cisplatin and radiation in two rat yolk sac tumour cell lines
      with different radiosensitivities in vitro.
AB  - We investigated the interaction of cisplatin and radiation in two rat yolk sac
      tumour cell lines with different radiosensitivities in vitro. The effects were
      assessed by clonogenic assay. D0 for the radiosensitivity of the radioresistant
      variant cell line, NMT-1R was 139 cGy, which was 1.3 times larger than that for
      the parent radiosensitive cell line, NMT-1 (D0 = 107 cGy). The concentration of
      cisplatin required to reduce colony formation by 50% at 1 h treatment (ID50 of
      cisplatin) was 0.25 microgram/ml for NMT-1, whereas that for NMT-1R was 1.0
      microgram/ml. Cisplatin potentiation of radiation sensitivity was manifested by
      the decrease in the slope of the radiation dose-response curve. D0's for NMT-1
      and NMT-1R were 83 and 100 cGy in combined treatment with ID50 of cisplatin
      immediately before radiation. The enhancement ratios of cisplatin were therefore
      1.30 for NMT-1 and 1.39 for NMT-1R respectively in D0. No different enhancement
      ratio for cisplatin was observed in the time course of combination treatment with
      cisplatin and radiation within the interval of 6 h. There was no clear change in
      cell cycle distribution within 6 h after treatment with ID50 of cisplatin for
      both cell lines. In conclusion, cisplatin had a synergistic effect on both cell
      lines which was independent of the time course and sequence in combination with
      radiation within 6 h.

PMID- 8980674
TI  - Chelation therapy by DFO-HOPO and 3,4,3-LIHOPO for injected Pu-238 and Am-241 in
      the rat: effect of dosage, time and mode of chelate administration.
AB  - The effectiveness of the siderophore analogues DFO-HOPO (a hydroxypyridone
      derivative of desferrioxamine) and 3,4,3-LIHOPO (a linear tetrahydroxypyridinone)
      for the decorporation of 238Pu and 241Am from rat was studied. (1) Dosage-effect
      relationship. A similar treatment effect on Pu was achieved by single s.c.
      injection of 30 mumol kg-1 or by oral administration of 100 mumol kg-1 of either
      of the two ligands, provided the oral dose was administered earlier. In general,
      LIHOPO was more effective than DFO-HOPO: retention of Pu in the liver and bones
      was reduced by LIHOPO to < 10% of control values. No increase in renal retention
      of the actinides was observed. Whilst DFO-HOPO did not affect Am retention, a
      substantial reduction was achieved by LIHOPO. Removal effectiveness for injected
      LIHOPO on Pu was higher than that on Am, especially in the bones and after low
      ligand doses. Orally administered small doses of LIHOPO, however, mobilized more
      Am than Pu, both from the liver and the bone. (2) Time-effect relationship. The
      effectiveness of the injected ligands for Pu decreased exponentially with the
      time between exposure and treatment. With DFO-HOPO, the calculated half-times for
      decrease of mobilized fractions of Pu from the bone and liver were 5 and 12 h
      respectively. The effect of LIHOPO on Pu decreased much more slowly, with a half
      time of 3-4 weeks. For instance, a single injection of 30 mumol kg-1 LIHOPO at 10
      days post-Pu removed 30 and 50% activity from the bone and liver respectively.
      The removal effect of LIHOPO for Am in the liver decreased with time in the same
      way as for Pu but the mobilized fractions of skeletal and renal Am decreased from
      the first day with a half-time of only 8 and 4 days respectively.

PMID- 8980673
TI  - Threshold for radiation-related severe mental retardation in prenatally exposed A
      bomb survivors: a re-analysis.
AB  - Significant effects on the developing human brain of exposure to ionizing
      radiation are seen among individuals exposed in the 8th-25th week after
      ovulation. These effects, particularly in the highly vulnerable period of 8-15
      weeks after ovulation, manifest themselves most dramatically as an increased
      frequency of severe mental retardation. However, the distribution of cases of
      severe mental retardation suggests a threshold in the low-dose region. The 95%
      lower bound of the threshold in those survivors exposed 8-15 weeks after
      ovulation was zero for the individual data based on the simple linear model, and
      0.15 Gy based on the exponential linear model used in our previous report (1987),
      but the 95% lower bound of the threshold based on all of the data including 21
      additional cases with known doses appears to be 0.05 Gy using the maximum
      likelihood estimates derived from an exponential-linear model. The latter model
      was selected because it provides the best fit from the standpoint of the
      stableness and reasonableness of the estimates among the five models applied to
      the data. When two probably non-radiation-related cases of Down's syndrome are
      excluded from the 19 mentally retarded cases exposed 8-15 weeks post ovulation,
      the 95% lower bound of the threshold is in the range of 0.15-0.25 Gy based on the
      exponential-linear model used in 1987, but is in the range of 0.06-0.31 Gy when
      the more reasonable and better model applied here is used. For exposure in the 16
      25-week period based on the same model, the 95% lower bound of the threshold
      changed from 0.25 to 0.28 Gy, both with and without inclusion of the two probable
      non-radiation-related mentally retarded cases; one of these cases was probably
      familial in origin since there was a retarded sibling, and the other due to
      infection, since the individual had Japanese B encephalitis at age 4 years.

PMID- 8980676
TI  - Bent pseudoknots and novel RNA inhibitors of type 1 human immunodeficiency virus
      (HIV-1) reverse transcriptase.
AB  - The reverse transcriptase (RT) of the human immunodeficiency virus (HIV) is a
      proven target for therapeutic intervention of HIV infections. We have found
      several new RNA inhibitors of HIV-1 RT that differ significantly from the
      pseudoknot ligands found previously, along with a wide variety of pseudoknot
      variants. One pseudoknot variant and three novel ligands were studied in more
      detail. Each specifically inhibits DNA polymerization by HIV RT (half-maximal
      inhibition at 0.3 to 20 nM inhibitor), but not that of RTs derived from MMLV or
      AMV. The minimal binding element of each isolate was determined by deletion
      analysis and by gel electrophoresis of protein-bound, partially alkaline
      hydrolyzed RNA. Truncations of three of the isolates bound nearly as well as (or
      better than) the parental sequences, while most deletions in the fourth caused
      substantial disruption of binding. The truncated versions of two isolates were
      subjected to six rounds of secondary SELEX after resynthesizing them
      mutagenically. Patterns of conserved and covarying nucleotides yielded structural
      models consistent with 5' and 3' boundary determinations for these molecules.
      Among the four isolates studied in detail, the first is confirmed as being a
      pseudoknot, albeit with substantial structural differences as compared to the
      canonical pseudoknots identified previously. The second forms a stem-loop
      structure with additional flanking sequences required for binding. Tentative
      structural models for the other two isolates are presented. The minimal fully
      active truncations of each of these four isolates compete with each other and
      with a classical RNA pseudoknot for binding to HIV RT, suggesting that they all
      recognize the same or overlapping sites on the protein, in spite of their
      apparently dissimilar structures. We model their interactions with RT as
      mimicking the 40 to 45 degrees bend in dsDNA co-crystallized with RT.

PMID- 8980675
TI  - Dominant forces in the recognition of a transient folding intermediate of alpha
      lactalbumin by GroEL.
AB  - GroEL is known to retard the refolding of apo-alpha-lactalbumin by interacting
      with the molten globule state of the protein. In order to investigate the
      dominant forces in this interaction, the GroEL-affected kinetic refolding of apo
      alpha-lactalbumin from its acidic molten globule state was studied at different
      temperatures and in the presence of different kinds of monovalent cations at a
      fixed temperature (25 degrees C), by stopped-flow fluorescence measurements. The
      binding constant between GroEL and alpha-lactalbumin in the molten globule state
      was evaluated quantitatively from the kinetic refolding curves in the absence and
      presence of GroEL. The binding was found to be entropy-driven at room temperature
      and the heat capacity change for the binding was found to be largely negative (
      3.6 kJ mol-1.K-1), indicating that GroEL binds to alpha-lactalbumin through
      hydrophobic interactions. The study of the effect of different monovalent cations
      at various ionic strengths shows that the binding is strengthened by
      electrostatic screening by ions, demonstrating the importance of electrostatic
      interactions. The relationship of these results with a putative target
      recognition site of GroEL will be discussed.

PMID- 8980677
TI  - How AraC interacts specifically with its target DNAs.
AB  - Previous work indicates that one subunit of the AraC protein dimer binds to a DNA
      target araI1, of 17 base-pairs. We systematically substituted every base-pair in
      a synthetic araI1 target with the three possible alternatives and then tested
      binding of araI1 and of these 51 DNA targets to AraC by quantitative gel shift
      analysis in the presence of L-arabinose. We found that every substitution of the
      underlined bases reduces AraC binding tenfold or more: 5' TAGCATTTTTATCCATA 3'.
      Substitutions at other bases have little or no effect. In the absence of L
      arabinose we observed a sixfold reduction of binding of AraC to araI1. We have
      designated the 5' AGC sequence the A-box and the 5'TCCATA sequence the B-box. We
      synthesised DNA targets containing either two A or two B-boxes with the natural
      araI1-I2 spacing. Wild-type AraC binds both targets in the presence of L
      arabinose in a gel shift-experiment. In the absence of L-arabinose, AraC binds
      only to the double B-box. We then tested various AraC mutant proteins in the same
      way. S208A and H212A bind to the double B-box but not to the double A-box in the
      presence or absence of L-arabinose. D256A binds to the double A-box, but not to
      the double B-box, in the presence of L-arabinose but not in its absence. The
      implications of these results for the mechanism of AraC induction by L-arabinose
      are discussed.

PMID- 8980678
TI  - Variable structures of Fis-DNA complexes determined by flanking DNA-protein
      contacts.
AB  - The Fis protein from Escherichia coli and Salmonella typhimurium regulates many
      diverse reactions including recombination, transcription, and replication and is
      one of the most abundant DNA binding proteins present in the cell under certain
      physiological conditions. As a specific regulator, Fis binds to discrete sites
      that are poorly related in primary sequence. Analysis of DNA scission by a
      collection of Fis conjugates to 1,10-phenanthroline-copper combined with
      comparative gel electrophoresis has shown that the structures of Fis-DNA
      complexes are highly variable, displaying overall DNA curvatures that range from
      < or = 50 degrees to > or = 90 degrees. This variability is primarily determined
      by differential wrapping of flanking DNA around Fis. By contrast, DNA bending
      within the core recognition regions appears similar among the binding sites that
      were analyzed. Flanking DNA contacts by Fis depend on the nucleotide sequence and
      are mediated by an electrostatic interaction with arginine 71 and a hydrogen bond
      with asparagine 73, both of which are located outside of the helix-turn-helix DNA
      binding motif. These contacts strongly influence the kinetics of binding. These
      data, combined with the crystal structure of Fis, have enabled us to generate new
      models for Fis-DNA complexes that emphasize the variability in DNA structures
      within the flanking regions.

PMID- 8980679
TI  - Characterization of a mutant RecA protein that facilitates homologous genetic
      recombination but not recombinational DNA repair: RecA423.
AB  - A recA mutant (recA423; Arg169-->His), with properties that should help clarify
      the relationship between the biochemical properties of RecA protein and its two
      major functions, homologous genetic recombination and recombinational DNA repair,
      has been isolated. The mutant has been characterized in vivo and the purified
      RecA423 protein has been studied in vitro. The recA423 cells are nearly as
      proficient in conjugational recombination, transductional recombination, and
      recombination of lambda red- gam- phage as wild-type cells. At the same time, the
      mutant cells are deficient for intra-chromosomal recombination and nearly as
      sensitive to UV irradiation as a recA deletion strain. The cells are proficient
      in SOS induction, and results indicate the defect involves the capacity of RecA
      protein to participate directly in recombinational DNA repair. In vitro, the
      RecA423 protein binds to single-stranded DNA slowly, with an associated decline
      in the ATP hydrolytic activity. The RecA423 protein promoted a limited DNA strand
      exchange reaction when the DNA substrates were homologous, but no bypass of a
      short heterologous insert in the duplex DNA substrate was observed. These results
      indicate that poor binding to DNA and low ATP hydrolysis activity can selectively
      compromise certain functions of RecA protein. The RecA423 protein can promote
      recombination between homologous DNAs during Hfr crosses, indicating that the
      biochemical requirements for such genetic exchanges are minimal. However, the
      deficiencies in recombinational DNA repair suggest that the biochemical
      requirements for this function are more exacting.

PMID- 8980681
TI  - DNA cleavage by the type IC restriction-modification enzyme EcoR124II.
AB  - Type I restriction-modification systems bind to non-palindromic, bipartite
      recognition sequences. Although these enzymes methylate specific adenine residues
      within their recognition sequences, they cut DNA at sites up to several thousand
      base-pairs away. We have investigated the mechanism of how EcoR124II, a type IC
      restriction-modification system, selects the cleavage site. Restriction studies
      with different DNA constructs revealed that circular DNA requires only one non
      methylated recognition sequence to be cut, whereas linear DNA needs at least two
      such sites. Cleavage of linear DNA is independent of site orientation. Further
      investigations of the linear substrates revealed a mechanism whereby the double
      strand break is introduced between two recognition sequences. We propose a model
      for the selection of restriction sites by type I enzymes where two EcoR124II
      complexes bind to two recognition sequences. Lack of methylation at a site
      stimulates the enzyme to translocate DNA on both sides of the recognition
      sequence. Thus the two complexes approach each other and, at the point where they
      meet, they interact to introduce a double-strand break in the DNA.

PMID- 8980680
TI  - The RecG branch migration protein of Escherichia coli dissociates R-loops.
AB  - The RuvAB and RecG proteins of Escherichia coli promote branch migration of
      Holliday junction intermediates in genetic recombination. Both are structure
      specific helicases that unwind and rewind DNA at the junction point. The helicase
      activities of these proteins were investigated using RNA:DNA hybrid molecules.
      RuvAB catalyses the unwinding of RNA:DNA partial duplexes of at least 218 bp in a
      reaction that requires both RuvA and RuvB, ATP and Mg2+. RecG failed to unwind
      these substrates even when the duplex region was reduced to 35 bp. In contrast,
      RecG rapidly removes a 218 nt RNA from an R-loop substrate, whereas RuvAB does
      not. RecG's ability to dissociate R-loops is correlated with an ability to reduce
      the copy number of pUC plasmids and other constructs based on the ColE1 replicon.
      Copy number is reduced severely when the plasmid carries recG+. RecG is assumed
      to reduce copy number by interfering with RNA II's ability to form an R-loop at
      the plasmid origin of replication and prime DNA synthesis. The dissociation of R
      loops by RecG is discussed in terms of the functions needed to promote
      recombination and to prime DNA replication at D-loops formed during the early
      stages of RecA-mediated recombination.

PMID- 8980682
TI  - Crystallographic evidence for C alpha-H...O=C hydrogen bonds in a collagen triple
      helix.
AB  - The crystal structure of the collagen triple-helical peptide (Pro-Hyp-Gly)4-Pro
      Hyp-Ala-(Pro-Hyp-Gly)5 shows evidence for the existence of interchain contacts
      between alpha-carbon hydrogens from Gly and Hyp residues, and carbonyl groups
      from Gly and Pro residues on neighboring chains. The geometrical disposition of
      these contacts makes it reasonable to describe them as C alpha-H...O=C hydrogen
      bonds. Two repetitive patterns can be identified, and one of them is identical to
      a similar type of interaction reported recently for beta-sheets in globular
      proteins, which suggests a more universal character for C-H...O hydrogen bonds in
      building protein secondary structure elements. They are presumably much weaker in
      energy than the interchain N-H...O=C hydrogen bonds responsible for the alignment
      of the three chains in the collagen triple helix, and therefore their
      contribution will be a small but cooperative decrease on the total interchain
      hydrogen bonding energy.

PMID- 8980683
TI  - The crystal structure of horse deoxyhaemoglobin trapped in the high-affinity (R)
      state.
AB  - Co-operative oxygen binding by the vertebrate haemoglobins arises from an
      equilibrium between a quaternary structure with low affinity (T), favoured in the
      absence of ligand, and a high affinity form (R) adopted by the fully ligated
      protein. While R state haemoglobin has an oxygen affinity close to that of
      isolated subunits, the affinity of the T state is roughly 300-fold lower. The
      mechanism by which the T state restrains ligand binding, and the pathway of the
      quaternary transition, have been largely revealed by detailed crystallographic
      analyses of a number of haemoglobin molecules in the equilibrium states, as well
      as intermediate forms of the T state including partially ligated species. The
      ligation intermediates of the R state, however, have not been as well
      characterized structurally. We report here the crystal structure of one such
      intermediate species, namely, horse deoxyhaemoglobin in the R state, at 1.8 A
      resolution. While ligand binding in the T state may result in unfavourable
      stereochemistry in and around the haem-ligand complex, the more plastic R
      structure appears to accommodate equally well both liganded and ligand-free haem.
      Loss of ligand at the R state haem results in movements of the haem and shifts of
      the FG corners, which form characteristic intersubunit contacts that distinguish
      the quaternary states. The shifts are comparable in magnitude to the
      corresponding movements associated with de-ligation in the T state, although they
      differ in direction. These and other differences illustrate how the structural
      changes in the haem pocket are communicated to the subunit interfaces and how the
      movements that can occur in the R state may be impeded in the T state.

PMID- 8980684
TI  - Solution structure of a parallel left-handed double-helical gramicidin-A
      determined by 2D 1H NMR.
AB  - The structure of a parallel left-handed double-helical form of gramicidin was
      detected by circular dichroism spectroscopy and determined using 500 and 600 MHz
      NMR in CaCl2/methanol solution. Measurements of TOCSY, DQF-COSY and NOESY spectra
      were converted into 604 distance and 48 torsional angle constraints for structure
      calculations. Stereospecific assignments and chi 1 angles were calculated using
      3J alpha beta, d alpha beta (i,i), dN beta(i,i) and dN gamma(i,i). chi 2 angles
      were determined using d alpha beta(i,i), dN beta(i,i), d beta delta(i,i), dN
      gamma(i,i) and d alpha gamma(i,i). The calculations of initial structures were
      performed using the distance geometry/simulated annealing method in XPLOR. The
      initial structures were further refined and energy minimized using simulated
      annealing/molecular dynamics methods. Back-calculations for every generated
      structure were also performed to check their consistency with the experimental
      data. 187 final structures with no violations above the threshold conditions
      (0.05 A, 5 degrees, 5 degrees, 0.5 A and 5 degrees for bonds, angles, improper,
      NOE and cdihe, respectively) were produced from the 200 initial structures.
      Twenty structures with the lowest NOE energies were used for further analysis.
      The average r.m.s. deviations for the 20 structures are 0.64 A for backbone and
      1.1 A for all non-hydrogen atoms. Gramicidin in this form, with approximately 5.7
      residues per turn, is a parallel double helical dimer. The length along the helix
      axis is about 30 A and the inner pore diameter varies from 1 to 2 A. It is
      different from all other gramicidin structures determined to date. The presence
      of Ca2+ stabilises a conformation that prevents the binding of monovalent
      cations. It is likely that this structure is related to a non-channel, antibiotic
      role of gramicidin.

PMID- 8980685
TI  - Coupling between folding and ionization equilibria: effects of pH on the
      conformational preferences of polypeptides.
AB  - A new approach to the conformational study of polypeptides is presented. It
      considers explicitly the coupling between the conformation of the molecule and
      the ionization equilibria at a given pH value. Calculations of the solvation free
      energy and free energy of ionization of a 17-residue polypeptide are carried out
      using a fast multigrid boundary element method (MBE). The MBE method uses an
      adaptive tessellation of the molecular surface by boundary elements with non
      regular size to solve the Poisson equation rapidly, and with a high degree of
      accuracy. The MBE method is integrated into the ECEPP (Empirical Conformational
      Energy Program for Peptides) algorithm to compute the coupling between the
      ionization state and the conformation of the molecule. This approach has been
      applied to study the conformational preference of a short polypeptide for which
      the available NMR and CD experimental data indicate that conformations containing
      a right-handed alpha-helical segment are energetically more favorable at low
      values of pH. The results of calculations using the present method agree quite
      well with experiments, in contrast to previous applications with standard
      techniques (using pre-assigned charges at each pH) that were not able to
      reproduce the experimental findings. Also, it is shown how the coupling to the
      conformation leads to different degrees of ionization of a given type of residue,
      for example glutamic acid, at different positions in the amino acid sequence, at
      any given pH. The results of this study provide a sound basis to discuss the
      origin of the stability of polypeptide conformations, and its dependence on the
      environmental conditions.

PMID- 8980686
TI  - Hyperthermophile protein folding thermodynamics: differential scanning
      calorimetry and chemical denaturation of Sac7d.
AB  - Recombinant Sac7d protein from the thermoacidophile Sulfolobus acidocaldarius is
      shown to be stable towards acid, thermal and chemical denaturation. The protein
      maintains a compact native fold between pH 0 and 10 in 0.3 M KCl and 25 degrees C
      as indicated by near and far UV circular dichroism spectra. Thermal unfolding
      followed by differential scanning calorimetry (DSC) occurs as a reversible, two
      state transition from pH 0 to 10, with a maximal Tm of 90.7 degrees C between pH
      5 and 9. At pH 0 the protein unfolds with a Tm of 63.3 degrees C. Plots of the
      enthalpy of unfolding as a function of Tm are linear and yield an anomalously low
      delta Cp of 497 (+/-20) cal deg-1 mol-1 using the Kirchhoff relation. Guanidine
      hydrochloride and urea-induced chemical denaturation of Sac7d occur reversibly
      and can be followed by circular dichroism. Global non-linear regression of the
      chemical denaturation data constrained by DSC determined values for delta Hm and
      Tm yields a delta Cp of unfolding of 858 (+/-21) cal deg-1 mol-1. The higher
      delta Cp is in good agreement with that predicted from the buried polar and
      apolar surface areas using the NMR solution structure. It is similar to values
      reported for mesophile proteins of comparable size, indicating that the packing
      and change in solvent-accessible surface area on unfolding are not unusual.
      Similarly, guanidine hydrochloride and urea m-values are in good agreement with
      those expected for a protein of 66 residues. Possible explanations for the
      difference in delta Cp determined by application of the Kirchhoff relation to DSC
      data and that determined by the global fit are discussed. Protein stability
      curves defined by either delta Cp values are similar to those observed for small
      mesophile proteins. Although the protein is thermally stable, it is marginally
      stable thermodynamically with a free energy of unfolding of 1.6 (+/-0.1) kcal mol
      1 at the growth temperature of 80 degrees C. The large number of potential ion
      pairs on the surface of this hyperthermophile protein do not result in an
      inordinate increase in stability. Post-translational modification, possibly
      lysine monomethylation, appears to be the single most important stabilizing
      factor that distinguishes the native hyperthermophile protein from small
      mesophile proteins. Additional stabilization in vivo is expected from compatible
      osmolytes (polyamines) and DNA-binding.

PMID- 8980687
TI  - The burst-phase intermediate in the refolding of beta-lactoglobulin studied by
      stopped-flow circular dichroism and absorption spectroscopy.
AB  - The kinetics of the guanidine hydrochloride-induced unfolding and refolding of
      bovine beta-lactoglobulin, a predominantly beta-sheet protein in the native
      state, have been studied by stopped-flow circular dichroism and absorption
      measurements at pH 3.2 and 4.5 degrees C. The refolding reaction was a complex
      process composed of different kinetic phases, while the unfolding was a single
      phase reaction. Most notably, a burst-phase intermediate of refolding, which was
      formed during the dead time of stopped-flow measurements (approximately 18 ms),
      showed more intense ellipticity signals in the peptide region below 240 nm than
      the native state, yielding overshoot behavior in the refolding curves. We have
      investigated the spectral properties and structural stability of the burst-phase
      intermediate and also the structural properties in the unfolded state in 4.0 M
      guanidine hydrochloride of the protein and its disulfide-cleaved derivative. The
      main conclusions are: (1) the more intense ellipticity of the intermediate in the
      peptide region arises from formation of non-native alpha-helical structure in the
      intermediate, apparently suggesting that the folding of beta-lactoglobulin is not
      represented by a simple sequential mechanism. (2) The burst-phase intermediate
      has, however, a number of properties in common with the folding intermediates or
      with the molten globule states of other globular proteins whose folding reactions
      are known to be represented by the sequential model. These properties include:
      the presence of the secondary structure without the specific tertiary structure;
      formation of a hydrophobic core; broad unfolding transition of the intermediate;
      and rapidity of formation of the intermediate. The burst-phase intermediate of
      beta-lactoglobulin is thus classified as the same species as the molten globule
      state. (3) The circular dichroism spectra of beta-lactoglobulin and its disulfide
      cleaved derivative in 4.0 M guanidine hydrochloride suggests the presence of the
      residual beta-structure in the unfolded state and the stabilization of the beta
      structure by disulfide bonds. Thus; if this residual beta-structure is part of
      the native beta-structure and forms a folding initiation site, the folding
      reaction of beta-lactoglobulin may not necessarily be inconsistent with the
      sequential model. The non-native alpha-helices in the burst-phase intermediate
      may be formed in an immature part of the protein molecule because of the local
      alpha-helical propensity in this part.

PMID- 8980688
TI  - Significant improvement in accuracy of multiple protein sequence alignments by
      iterative refinement as assessed by reference to structural alignments.
AB  - The relative performances of four strategies for aligning a large number of
      protein sequences were assessed by referring to corresponding structural
      alignments of 54 independent families. Multiple sequence alignment of a family
      was constructed by a given method from the sequences of known structures and
      their homologues, and the subset consisting of the sequences of known structures
      was extracted from the whole alignment and compared with the structural
      counterpart in a residue-to-residue fashion. Gap-opening and -extension penalties
      were optimized for each family and method. Each of the four multiple alignment
      methods gave significantly more accurate alignments than the conventional
      pairwise method. In addition, a clear difference in performance was detected
      among three of the four multiple alignment methods examined. The currently most
      popular progressive method ranked worst among the four, and the randomized
      iterative strategy that optimizes the sum-of-pairs score ranked next worst. The
      two best-performing strategies, one of which was newly developed, both pursue an
      optimal weighted sum-of-pairs score, where the pair weights were introduced to
      correct for uneven representations of subgroups in a family. The new method uses
      doubly nested iterations to make alignment, phylogenetic tree and pair weights
      mutually consistent. Most importantly, the improvement in accuracy of alignments
      obtained by these iterative methods over pairwise or progressive method tends to
      increase with decreasing average sequence identity, implying that iterative
      refinement is more effective for the generally difficult alignment of remotely
      related sequences. Four well-known amino acid substitution matrices were also
      tested in combination with the various methods. However, the effects of
      substitution matrices were found to be minor in the framework of multiple
      alignment, and the same order of relative performance of the alignment methods
      was observed with any of the matrices.

PMID- 8980689
TI  - A new possible parameter for the detection of aneuploidy inducing substances: the
      analysis of qualitative and quantitative abnormalities of the spindle apparatus.
AB  - In the present study, compared to other cytogenetic methods, we measured the
      number of aneuploid cells directly by analyzing anomalies of the mitotic spindle.
      Qualitative and quantitative abnormalities of the mitotic spindle apparatus in
      transformed and non-transformed cell lines in vitro were classified. We treated
      the different cell lines with well known aneugenic agents as Benomyl and
      Griseofulvin and investigated the mitotic spindle under different experimental
      conditions. The spindle apparatus was stained by indirect immunofluorescence and
      the chromatin was counterstained by fluorescent dyes. The mitotic spindle showed
      a great sensitivity to the aneuploidy-inducing substances used in our
      experiments. The spindle-disturbing effect of the tested substances was
      demonstrated to be dose- dependent. The morphological alterations appeared to be
      independent of the aneuploidy-inducing test substance used, but showed a relation
      to the dose and length of treatment. Thus, the analysis of the mitotic spindle
      may be a useful screening parameter for the detection of aneuploidy-inducing
      substances and further investigations will provide additional results to specific
      parameters.

PMID- 8980690
TI  - Antimutagens from Plumeria acuminata Ait.
AB  - Four isolates, A1, C1, D3, and F2, from the ethanol extract of the green leaves
      of Plumeria acuminata Ait, showed antimutagenic activity. The antimutagens were
      isolated from the bioactive hexane and carbon tetrachloride fractions following a
      bioactivity-directed fractionation scheme and using the micronucleus test to
      monitor the antimutagenic activities. Structure elucidation studies indicated
      that C1 is stigmast-7-enol[1], D3 is lupeol carboxylic acid [2] and F2 is ursolic
      acid [3]. The structure of A1 was not fully elucidated but MS data suggested that
      it contained a long hydrocarbon chain. At a dosage of 2 mg isolate/25 g mouse, A1
      reduced the number of micronucleated polychromatic erythrocytes (MPCE) induced by
      the mutagen, mitomycin C, by 75%, C1 by 80%, D3 by 57%, and F2 by 76%. Compound
      A2 was also isolated but was found inactive. Its structure was identified to be
      lupeol acetate [4].

PMID- 8980691
TI  - Chromosome analysis of peripheral lymphocytes from persons exposed to radioactive
      fallout in Norway from the Chernobyl accident.
AB  - Chromosome analysis of peripheral lymphocytes from two Norwegian populations (44
      reindeer herding South samis from Roros and Snasa, 12 sheep farmers from Valdres)
      exposed to fallout from the Chernobyl accident were made. The doses from caesium
      through the years 1987-1991 were calculated based on whole-body measurements
      134Cs and 137Cs giving a total cumulative mean internal dose of 5.54 mSv for the
      total group of 56 persons. Chromosome aberrations were within the normal range
      when compared with historical controls with the exception of dicentrics (0.3% per
      cell, which is a 10-fold increase) and rings (0.07% per cell). A dose-dependent
      increase in dicentrics and rings based on caesium exposure was not observed.

PMID- 8980692
TI  - Mechanism of antimutagenic action of (+)-catechin against the plant-activated
      aromatic amine 4-nitro-o-phenylenediamine.
AB  - Aromatic amines are activated into mutagens by both animal and plant systems. For
      plant-activated aromatic amines an important step in this process involves
      peroxidase enzymes. 4-nitro-o-phenylenediamine (NOP) is a well known direct
      acting mutagen that can be enhanced in mutagenic potency by intact plant cells
      and also by isolated peroxidase enzymes. This activation process is inhibited by
      several different chemical agents including potassium cyanide (KCn), a known
      peroxidase inhibitor, and (+)-catechin. In our laboratory both KCn and (+)
      catechin inhibited peroxidase-mediated NOP activation into a Salmonella mutagen.
      However, while KCn demonstrated strong peroxidase enzyme inhibition (as measured
      biochemically), (+)-catechin showed only minimal inhibition of peroxidase.
      Experiments comparing NOP direct and plant-activated mutagenic activity to
      different Salmonella strains (in the presence and absence of (+)-catechin)
      suggest that (+)-catechin may inhibit the mutagenic process by limiting O
      acetyltransferase (OAT) activity in Salmonella. OAT activity in Salmonella is a
      required process for mutations to be induced following treatment with NOP and
      other aromatic amines.

PMID- 8980693
TI  - Micronucleus formation in V79 cells treated with respirable silica dispersed in
      medium and in simulated pulmonary surfactant.
AB  - Chinese hamster lung fibroblasts (V79 cells) were challenged with respirable
      silica particles using an in vitro genotoxicity assay. Two particle sizes of
      crystalline quartz and a non-crystalline silica were assayed for induction of
      micronuclei (MN) in V79 cells. Some of the silica dusts used were pretreated with
      simulated pulmonary surfactant to model in vivo exposure conditions. The results
      showed that both crystalline and non-crystalline silica dispersed in medium (MEM)
      induced MN formation in a dose-dependent manner. Crystalline silica was more
      active in this assay than non-crystalline silica on a mass basis. The results
      also show that the frequency of micronucleated cells in cultures treated with
      surfactant-coated silica was not significantly different from that of the non
      treated control cultures. These results seem to indicate that silica can cause
      chromosomal aberrations and/or aneuploidies in V79 cells; however, pretreatment
      of silica particles with simulated pulmonary surfactant reduces or delays
      genotoxicity in this assay.

PMID- 8980694
TI  - Genetic toxicity of cytokines.
AB  - Review of the literature shows that such cytokines as human interferons alpha and
      gamma, tumor necrosis factor alpha, epidermal growth factor and interleukin-2 may
      exhibit genotoxic properties in human peripheral blood lymphocyte cultures. For
      all above cytokines, except interleukin-2, parabolic-like relationship between
      the dose and the frequency of sister chromatid exchanges was found. Although the
      mechanisms of these genotoxic actions remain largely unknown, generation of free
      radicals or interaction with enzymes such as DNA topoisomerase II may be
      suspected. Human interferon alpha also may be considered as an antimutagenic
      compound in human cells. Human tumor necrosis factor alpha has been reported to
      enhance cytotoxicity and DNA fragmentation produced by DNA topoisomerase II
      targeted anticancer drugs. At the same time, it has some radio- and
      chemoprotective properties in vitro and in vivo. Despite these facts, the
      question about genotoxicity of cytokines is not answered. Some problems must be
      resolved before receiving the final answer. First, much more cytokines must be
      tested for their genotoxic activity. Second, appropriate test-systems must be
      designed. Third, genotoxicity studies of cytokines must account for cytokine
      interaction in the cytokine network as well as for such cytokine-induced effects
      as cytotoxicity and apoptosis. Fourth, in each case, it is necessary to have
      experimental evidence that observed genotoxic effects were caused by cytokine
      under investigation and not by the other factors.

PMID- 8980695
TI  - Micronucleated erythrocytes in splenectomized patients with and without
      chemotherapy.
AB  - The purpose of the present study was to investigate the range of micronucleated
      erythrocytes (MNE) in peripheral blood from splenectomized patients with and
      without genotoxic chemotherapy. The erythrocytes were stained with Wright and
      Giemsa for microscopic observation. To estimate the number of MNE, two series of
      10000 erythrocytes per sample were analyzed and averaged. The results expressed
      as mean +/- standard deviation were as follows: control patients with genotoxic
      chemotherapy (n = 6) 2.5 +/- 1.5 (range 1 to 5 MNE); splenectomized patients with
      genotoxic chemotherapy (n = 7) 65.2 +/- 17.7 (range: 47-108) MNE and
      splenectomized patients without genotoxic chemotherapy (n = 13) 29.5 +/- 5.8 MNE;
      (range: 18.5-35.6). The MNE number in the patients treated with genotoxic
      chemotherapy depended on the type of drugs utilized: cyclophosphamide,
      mitoxantrone, vincristine, busulphan, cytosine arabinoside and hydroxyurea. Upon
      these results, it is suggested that splenectomized people could be useful in
      monitoring exposures, and the baseline MNE level would serve as each person's pre
      exposure control when either chronic or acute exposure to environmental mutagens
      is investigated.

PMID- 8980696
TI  - Chrysotile asbestos fibers mediate homologous recombination in Rat2 lambda
      fibroblasts: implications for carcinogenesis.
AB  - Asbestos fibers are widespread environmental carcinogens whose mutagenicity is
      now established. Nonetheless, the molecular nature of these mutations and the
      mechanisms by which they accelerate carcinogenesis remain poorly understood. We
      have assessed the ability of asbestos fibers to promote homologous recombination,
      a potent mechanism for generating intrachromosomal rearrangements, such as
      deletions, and mitotic recombination. For this, we have developed a new assay
      which determines the extent to which a marker gene present in DNA introduced by
      asbestos can recombine with homologous genes residing in a transfected cell. We
      have demonstrated that Calidria chrysotile fibers are mutagenic and are able to
      mediate transfection of molecularly marked mutant lacI genes in a manner that
      results in their preferential recombination with homologous wild-type genes in
      the transfected cell. Asbestos induced recombination events may play a
      significant role in asbestos mutagenesis and carcinogenesis, and promotion of
      recombination may underlie the well-recognized synergy of asbestos with other
      carcinogens.

PMID- 8980697
TI  - Induction of sister chromatid exchange by 3,4-expoxybutane-1,2-diol in cultured
      human lymphocytes of different GSTT1 and GSTM1 genotypes.
AB  - The induction of sister chromatid exchanges (SCEs) by a 48-h treatment with 3,4
      epoxybutane-1,2-diol (EBD), a metabolite of 1,3-butadiene, was studied in whole
      blood lymphocyte cultures of 22 human donors with known genotypes of two
      polymorphic glutathione S-transferases (GSTs), GSTT1 and GSTM1. For both genes,
      donors representing a homozygous 'null' genotype lacking the respective GST gene
      and isozyme and a 'positive' genotype with at least one intact gene and GST
      activity were included. The mean frequencies of SCE/cell were similar in all
      genotype groups: GSTT1 null (n = 10) (mean 22.0 for 250 microM and 32.9 for 500
      [corrected] microM of EBD), GSTT1 positive (n = 14) (21.3 and 34.6,
      respectively), GSTM1 null (n = 10) (20.3 and 33.5) and GSTM1 positive donors (n =
      15) (20.6 and 34.8). At 500 microM concentration of EBD, the lymphocyte cultures
      of all donors showed a significantly decreased replication index. No differences
      in EDB-induced SCEs or in replication index could be associated with the GSTM1
      and GSTT1 genotypes either separately or in combination. When SCE induction by
      EBD was compared to that of two other known epoxide metabolites of butadiene,
      1,2:3,4-diepoxybutane (DEB) was effective at concentrations over two orders of
      magnitude lower than EBD or 1,2-epoxy-3-butene (MEB). It is concluded that EBD is
      an efficient inducer of SEC in cultured human lymphocytes, although not quite as
      effective as MEB and clearly less effective than DEB. Contrary to previous
      findings with DEB and MEB, the polymorphic GSTM1 and GSTT1 do not appear to be
      involved in the detoxification of EBD in human lymphocytes.

PMID- 8980698
TI  - Sister chromatid exchange frequency in inhabitants exposed to asbestos in Turkey.
AB  - Pleural mesothelioma, lung cancer, pleural calcification and fibrosis have been
      observed among inhabitants of the villages in Ivriz-Zanapa valley in Turkey.
      Earlier reports have stated that these endemic pathological conditions are caused
      by the inhalation of actinolite asbestos, a mineral commonly used
      indiscriminately to paint the walls and floors of houses. In the present study,
      40 inhabitants in Yassikaya village in Ivriz-Zanapa valley and 20 controls were
      further investigated. The peripheral blood lymphocytes were cultured and
      harvested at 72 h for sister chromatid exchange (SCE) frequency. Inhabitants had
      a raised mean SCE rate compared with a control population.

PMID- 8980699
TI  - Okadaic acid treatment induces DNA adduct formation in BHK21 C13 fibroblasts and
      HESV keratinocytes.
AB  - Okadaic acid (OA), a toxin involved in diarrhetic shellfish poisoning (DSP), has
      been shown to be a potent tumor promoter in mouse skin and glandular stomach.
      However, more recent studies tended to show that OA can also act as a genotoxic.
      In this study, using the 32P-postlabelling method, DNA adduct formation was
      obtained in two cell lines (BHK21 C13 fibroblasts and HESV keratinocytes) after
      treatment by OA for 24 h with a dose range between 0.01 and 5 nM. Nineteen
      adducts were observed with BHK21 C13 cells and 15 with HESV ones. Low doses did
      not show adduct formation. Intermediate doses have given the most important
      number of adducts and with higher doses, the number of adducts decreased dose
      dependently. Ten adducts were similar in the two strains while 9 were specific of
      BHK21 C13 cell line and 5 of HESV one. The highest total DNA adduct level from
      origin parts was estimated at 95.6 adducts/10(9) nucleotides for BHK21 C13
      fibroblasts (1 nM OA treatment) and 31.1 adducts/10(9) nucleotides for HESV
      keratinocytes (0.5 nM OA treatment). In this case, the major adduct (number 3)
      represented 20% for the fibroblastic cell line and 30% for the keratinocytic
      strain. The genotoxic effect of OA showed in this study should lead to a more
      careful survey of DSP outbreaks.

PMID- 8980700
TI  - Comparisons on chemically-induced mutagenicity among four bacterial strains,
      Salmonella typhimurium TA102 and TA2638, and Escherichia coli WP2/pKM101 and WP2
      uvrA/pKM101: collaborative study I.
AB  - A collaborative study of chemically-induced mutagenicity was performed using the
      four bacterial strains Salmonella typhimurium TA102 and TA2638 and Escherichia
      coli WP2/pKM101 and WP2 uvrA/pKM101 in order to compare the specific spectrum of
      response to chemicals among the four strains and to determine the usefulness
      (sensitivity) of each strain. Twenty laboratories participated in this study. As
      the first step, 29 compounds were tested for mutagenicity using the plate
      incorporation method with or without metabolic activation. The compounds
      consisted of 12 chemicals judged previously positive only in E. coli WP2
      uvrA/pKM101, 15 of their derivatives, and the 2 well-known mutagens hydrazine and
      formaldehyde. The strains and the chemicals were sent from a central source to
      each laboratory. The tests were performed in two laboratories per chemical.
      Concerning the result with each strain, the number of chemicals which showed
      mutagenic activity were 10, 7, 9 and 17 in TA102, TA2638, WP2/pKM101 and WP2
      uvrA/pKM101, respectively. Among these 29 compounds tested, no qualitative
      difference in the response to chemicals among the four strains was observed with
      17 compounds, being 12 negative chemicals and 5 positive chemicals. The remaining
      12 compounds showed varying results among the four strains. On the comparison of
      TA102 and WP2 uvrA/pKM101, the same qualitative response to chemicals was
      observed with 22 compounds. Thus, although compounds tested in this study were
      selected, partly based on a previously-judged positive response only in E. coli
      WP2 uvrA/pKM101, 76% of test chemicals showed the same sensitivity in TA102, 7
      chemicals (24%) were only positive in the E. coli strains. Of these 7 chemicals,
      5 were the acrylic acid ester derivatives and the chloroacetic acid ester
      derivatives possessing a common structure of a functional group esterized between
      acid and alcohol with two or more carbon radicals.

PMID- 8980701
TI  - Biomarkers of effect in evaluating metalaxyl cocarcinogenesis. Selective
      induction of murine CYP 3A isoform.
AB  - The ability of metalaxyl, whose mutagenic/cocarcinogenic activity has as yet not
      been clarified, to affect specific biomarkers related to non-genotoxic
      cocarcinogenesis, was investigated. Several CYP-dependent reactions have been
      studied in liver, kidney and lung microsomes derived from male and female Swiss
      Albino CD1 mice treated i.p. with single (200 or 400 mg/kg b.w.) or repeated (200
      mg/kg b.w., 3 days) administrations of fungicide. No significant changes in both
      absolute and relative liver, kidney and lung weights were observed after
      metalaxyl treatment. Although a single dose did not significantly affect the
      considered monooxygenases, a clear example of selective CYP3A induction was
      recorded in different tissues after repeated treatment. A 3 approximately -fold
      increase in CYP3A isozymes, probed by N-demethylation of aminopyrine, was
      observed in the liver (both sexes). Again, a 5 approximately -fold increase
      (averaged between male and female) in this oxidase activity was present in the
      kidney. No significant change of the selected biomarkers was observed in the
      lung. A weak, but significant reduction of CYP2B1 isoform in liver (male) was
      also recorded. Liver and kidney CYP3A overexpression was corroborated by means of
      Western immunoblotting analysis using rabbit polyclonal antibodies anti-CYP3A1/2.
      Northern blotting analysis with CYP3A cDNA biotinylated probe showed that, in the
      liver, the expression of this isozyme is regulated at the mRNA level. On the
      whole, these data seem to indicate the cotoxic and cocarcinogenic potential of
      this fungicide.

PMID- 8980702
TI  - A plasmid rescue to investigate mutagenesis in transgenic D. melanogaster.
AB  - We present a plasmid rescue from transgenic Drosophila to study spontaneous and
      mutagen-induced mutations in vivo. Transgenic Drosophila lines were established
      by transformation with a shuttle vector containing the bacterial lacZ gene as a
      target for mutagenesis. The target gene can be recovered into bacteria by
      restriction endonuclease treatment of total genomic DNA, followed by ligation of
      the recircularized shuttle vectors. The resulting circular plasmids are then
      transformed back into E. coli lacZ- mutants, where the activity of the lacZ genes
      is scored on the induction substrate X-Gal. The number of inactivated versus
      intact lacZ genes directly indicates the mutation frequency. By the described
      target gene rescue procedure up to 5000 lacZ gene copies can be rescued from one
      fly routinely. Spontaneous background mutation rates using this system are 2.6 +/
      0.6 x 10(-4). Treatment of larvae with ethylnitrosourea (ENU) resulted in a dose
      dependent increase of the mutation frequency to 4.8 +/- 0.6 x 10(-4) for 0.5 mM
      and 6.9 +/- 1.2 x 10(-4) for 1 mM ENU, respectively.

PMID- 8980703
TI  - Micronucleus test of erythrocytes and lymphocytes in the blood of the people
      living in the radiation pollution zone as a result of the accident at the
      Siberian chemical plant on April 6, 1993.
AB  - We have carried out analysis of the number of blood erythrocytes and lymphocytes
      with micronuclei in the inhabitants of four settlements located near the place of
      the accident which happened at the atomic power station of the Siberian chemical
      plant (Tomsk-7) on April 6, 1993. In all cases, the people examined showed a
      considerable increase in the number of cells with micronuclei as compared with
      the control. We observed the same people for 2 years and found a gradual decrease
      in the number of cells with micronuclei. This study shows that people born
      between 1963-1970 have a much higher level of cells with micronuclei, which we
      tend to see as a result of the radiation accident at the Siberian chemical plant
      in 1963. The data we have obtained allow us to conclude that penetration of
      radionuclides into the human organism in the prenatal and early postnatal periods
      can lead to the formation of stable clones of erythroid cells with micronuclei
      and a higher level of erythrocytes with micronuclei which can remain in the blood
      for a long time.

PMID- 8980704
TI  - Bio-antimutagenic activity of green tea catechins in cultured Chinese hamster V79
      cells.
AB  - The antimutagenic effects of green tea catechins, (-)-epicatechin gallate (ECg)
      and (-)-epigallocatechin gallate (EGCg) on induction of 6-thioguanine (6TG)
      resistant mutations induced by 4-nitroquinolin 1-oxide (4NQO) were found in
      cultured Chinese hamster V79 cells. The antimutagenic activity of catechins was
      found only when cells were post-treated with catechins during the mutation
      expression time after treatment with 4NQO, and not found by simultaneous
      treatments with 4NQO and catechins. This bioantimutagenic activity of catechins
      were not observed in ethyl methanesulfonate (EMS)-induced mutations. This
      suggests that the antimutagenic effects of catechins may act intracellularly as
      bio-antimutagenic blocking agent or suppressive agent. These catechins had no
      effects on the cytotoxic activity of 4NQO in V79 cells, whether catechins were
      used in simultaneous treatment with or in post-treatment after 4NQO. This
      indicates that the antimutagenicity and anticytotoxicity to 4NQO may be caused by
      different mechanism(s).

PMID- 8980705
TI  - Large deletion detected with the Big Blue transgenic mouse mutagenesis assay.

PMID- 8980706
TI  - Incisional herniation of the bladder: CT findings.

PMID- 8980707
TI  - Accumulation of ochratoxin A in rat kidney in vivo and in cultivated renal
      epithelial cells in vitro.
AB  - In this study we determined the distribution of ochratoxin A (OTA) in renal
      tissue as well as its content and binding pattern in different cell types
      stemming from the proximal tubule (OK cells) and collecting duct (MDCK cells) of
      the kidney. To obtain the net amount of OTA in renal tissue, the relative amount
      in the vascular compartment was calculated and subtracted. After acute
      administration of OTA to male Wistar rats, the highest concentrations were
      detected in the papilla and inner medulla. Concentrations in the outer medulla
      and in the cortical tissue were 50% lower. Sub-chronic (6 day) exposure to OTA
      resulted in a similar distribution in young rats (6 weeks old) but in a different
      distribution in adult rats (2 year old). Cultured MDCK-C11 cells (representing
      intercalated cells) showed a higher OTA content after 48 h of exposure to 1
      mumol/1 OTA than another MDCK cell subtype (MDCK-C7, representing principal
      cells) and OK cells. Additionally, the capability of cell extracts to bind OTA
      was the highest in MDCK-C11 cells followed by cell extracts of OK cells and cell
      extracts of MDCK-C7 cells. In two cell types studied, OK and MDCK-C11 cells, OTA
      was bound preferentially by organellar components and less by cytosolic ones.

PMID- 8980708
TI  - Increased 5-lipoxygenase metabolism in the lungs of human subjects exposed to
      ozone.
AB  - The environmental pollutant ozone, at sufficiently high levels, is known to
      induce pulmonary inflammation with resultant airway obstruction in normal
      subjects. Eicosanoids comprise one group of mediators released from alveolar
      macrophages which are involved in the pathogenesis of inflammatory lung diseases.
      We compared the effects of 2-h exposures to 0.4 ppm ozone and filtered air on
      pulmonary function and eicosanoid levels in bronchoalveolar lavage fluid in 11
      normal healthy volunteers. Subjects were exposed to a 6-fold increase in minute
      ventilation using an adjusted work load on a cycle ergometer. All subjects
      complained of cough and dyspnea, and demonstrated increased airway obstruction,
      and increased specific airway resistance following ozone exposure as compared to
      air exposure. Bronchoalveolar lavage cell count demonstrated a 9-fold increase in
      the number of neutrophils with a lesser reduction in the number of alveolar
      macrophages following ozone exposure. Notably, bronchoalveolar lavage fluid
      leukotriene (LT) C4 (8-fold) and to a lesser extent LTB4 (1.5-fold) levels were
      higher following ozone exposure compared to air control, with no change in
      prostaglandins. In a subset of four subjects, alveolar macrophage arachidonic
      acid metabolism was studied in vitro following separate in vivo exposures to both
      ozone and air. Alveolar macrophages obtained following ozone exposure released
      more 5-lipoxygenase (1.5-fold) metabolites, with no change in cyclooxygenase
      metabolites, than did cells obtained following air exposure. These observations
      document activation of the 5-lipoxygenase pathway in the lung following ozone
      exposure, and suggest that alveolar macrophages may participate in the generation
      of LT, whose actions promote airway inflammation and obstruction.

PMID- 8980710
TI  - The carcinogenicity of dichloroacetic acid in the male Fischer 344 rat.
AB  - The chlorinated acetic acids, in particular dichloroacetic acid (DCA), are found
      as chlorine disinfection by-products in finished drinking water supplies. DCA has
      previously been demonstrated to be a mouse liver carcinogen. Chronic studies are
      described in which male Fischer (F344) rats were exposed to DCA in their drinking
      water. In the first study, 28 day old rats were exposed to a regimen of 0.05, 0.5
      and 5.0 g/l DCA. When animals in the high dose group began to exhibit peripheral
      hind leg neuropathy, the dose was lowered in stages to 1 g/l. These animals were
      sacrificed at 60 weeks due to the severe, irreversible neuropathy and were not
      included in this analysis. The remaining groups of animals were treated for 100
      weeks. In the second study, rats were initially exposed to 2.5 g/l DCA which was
      lowered to 1 g/l after 18 weeks. The mean daily concentration (MDC) of 1.6 g/l
      was calculated over the 103 week exposure period. Time-weighted mean daily doses
      (MDD) based on measured water consumption were 3.6, 40.2 and 139 mg/kg bw/day for
      the 0.05, 0.5 and 1.6 g/l DCA respectively. Based upon the pathologic
      examination, DCA induced observable signs of toxicity in the nervous system,
      liver and myocardium. However, treatment related neoplastic lesions were observed
      only in the liver. A statistically significant increase of carcinogenicity
      (hepatocellular carcinoma) was noted at 1.6 g/l DCA. Exposure to 0.5 g/l DCA
      increased-hepatocellular neoplasia, (carcinoma and adenoma) at 100 weeks. These
      data demonstrate that DCA is an hepatocarcinogen to the male F344 rat.
      Calculation of the MDD at which 50% of the animals exhibited liver neoplasia
      indicated that the F344 male rat (approximately 10 mg/kg bw/day) is ten times
      more sensitive than the B6C3F1 male mouse (approximately 100 mg/kg bw/day). A "no
      observed effects level' (NOEL) of 0.05 g/l (3.6 mg/kg/day) was the same as for
      the mouse (3-8 mg/kg/day).

PMID- 8980709
TI  - Decreased liver type I 5'-deiodinase and increased brown adipose tissue type II
      5'-deiodinase activity in 2,3,7,8-tetrachlorobibenzo-p-dioxin (TCDD)-treated Long
      Evans rats.
AB  - The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied on the
      activity of type I 5'-deiodinase (5' DI) in liver and of type II 5'-deiodinase
      (5' DII) in brown adipose tissue (BAT) microsomes of Long-Evans rats. TCDD
      decreased the activity of liver 5' DI and increased that of BAT 5' DII. It also
      reduced the concentration of serum total thyroxine (T4) without affecting
      triiodothyronine (T3). These effects of TCDD on 5'-deiodinases and serum thyroid
      hormones are compatible with partial hypothyroidism. Based on our results, it is
      not possible to decide unequivocally whether TCDD affects thyroid hormone status
      and 5'-deiodination by a direct action or a feedback mechanism. However, these
      data are important because they demonstrate that TCDD affects thyroid status in a
      tissue-specific manner and that its effects on thyroid hormone metabolism are
      much more complex than currently assumed.

PMID- 8980711
TI  - The effect of carbon monoxide on oxygen metabolism in the brains of awake sheep.
AB  - Eight conscious chronically instrumented sheep were exposed to 1% inspired carbon
      monoxide (CO) for 35 min. In all sheep, carboxyhaemoglobin (COHb) levels at the
      end of the exposure were approximately 65%. Mean arterial blood pressure was
      unchanged with the exception of 2 sheep in which administration was stopped at 25
      min following the sudden onset of hypotension. Oxygen delivery to the brain was
      sustained throughout the administration of CO due to a significant increase in
      cerebral blood flow (CBF). There was no evidence of either a metabolic acidosis
      or of lactate production by the brain suggesting the brain did not become hypoxic
      during the time-course of this study. Despite the apparent lack of hypoxia,
      oxygen consumption by the brain fell progressively and the sheep showed
      behavioural changes which varied from agitation to sedation and narcosis. The
      mechanism of these changes was therefore probably unrelated to hypoxia, but may
      have been due to raised intracranial pressure or a direct effect of CO on brain
      function. It is proposed that the time-course of progressive CO poisoning
      includes a phase in which CBF is elevated, blood pressure is unchanged and the
      brain is normoxic despite high COHb levels, but that this situation can rapidly
      evolve into a phase of haemodynamic collapse and severe hypoxia.

PMID- 8980712
TI  - Characterisation of the toxic metabolite(s) of naphthalene.
AB  - The toxicity of naphthalene and its metabolites has been investigated in vitro.
      Both naphthalene and its metabolite 1-naphthol were bioactivated by human hepatic
      microsomes to metabolite(s) which were toxic to mononuclear leucocytes (MNL).
      However 1-naphthol was more cytotoxic than naphthalene (49.8 +/- 13.9% vs. 19.0
      +/- 10.0% cell death; P < 0.01), indicating that the toxicity of naphthalene is
      dependent on the bioactivation of 1-naphthol. CYP2E1-induced rat liver microsomes
      increased metabolism of naphthalene by 13% compared to control microsomes with a
      concomitant increase in both 1-naphthol and dihydrodiol formation. The
      cytotoxicity of naphthalene but not of 1-naphthol was increased by CYP2E1
      induction, indicating that separate enzymes are involved in the bioactivation of
      1-naphthol. The metabolites of 1-naphthol, 1,2-naphthoquinone (51.4 +/- 6.6% cell
      death) and 1,4-naphthoquinone (49.1 +/- 3.4% cell death) were directly toxic to
      MNL and depleted glutathione to 1.0% of the control levels. Both quinones were
      also genotoxic to human lymphocytes. In contrast, the primary metabolite of
      naphthalene, the 1,2-epoxide (0-100 microM) was neither cytotoxic nor genotoxic,
      and did not deplete glutathione. In conclusion, our data suggests that the
      cytotoxicity and genotoxicity of naphthalene is associated with the formation of
      quinones from 1-naphthol rather than naphthalene-1,2-epoxide.

PMID- 8980714
TI  - Abnormalities of the cortico-geniculate pathway in Siamese cats.

PMID- 8980713
TI  - Effects of ozone upon macrophage-interferon interactions.
AB  - Lung cell populations may be directly exposed to environmental airbone toxicants
      such as ozone (O3). Since pulmonary macrophages (M phi) play a pivotal role in
      host pulmonary immunocompetence, their function in this regard may be compromised
      by pollutant exposure thereby giving rise to an increased incidence of pulmonary
      disease. The current in vitro study was designed to provide some insight into
      possible mechanisms by which O3 induces decreased host pulmonary resistance
      against microbial pathogens. Specifically, this study investigated the impact of
      an acute O3 exposure upon the ability of a cultured mouse M phi cell line (WEHI
      3) to interact with, and respond to, the major M phi-activating cytokine,
      interferon-gamma (IFN gamma). The results of this study indicate that WEHI-3
      exposure to 1 ppm O3 for 4 h reduced both the binding of, and responsivity to,
      IFN gamma. Among the functional parameters affected by this inability to properly
      bind/respond to IFN gamma were: reactive oxygen intermediate production,
      phagocytic activity, and cellular calcium ion elevation; IFN gamma-enhanced
      expression of surface histocompatibility antigens was unaffected by O3 exposure.
      The reduced activity of any one of these critical M phi functions could provide a
      basis for previously-documented increases in microbial pathogen survival in the
      lungs, and overall compromise of host health following O3 exposure.

PMID- 8980715
TI  - A documentation of an age related increase in neuronal and axonal numbers in the
      stingray, Dasyatis sabina, Leseuer.

PMID- 8980716
TI  - Prenatal development of the cerebellar system in the rat. I. Cytogenesis and
      histogenesis of the deep nuclei and the cortex of the cerebellum.

PMID- 8980717
TI  - Prenatal development of the cerebellar system in the rat. II. Cytogenesis and
      histogenesis of the inferior olive, pontine gray, and the precerebellar reticular
      nuclei.

PMID- 8980718
TI  - The corticopontine projection from the visual cortex of the cat: an
      autoradiographic investigation.

PMID- 8980719
TI  - The neurons in the gelatinosal complex (Laminae II and III) of the monkey (Macaca
      mulatta): a Golgi study.

PMID- 8980720
TI  - The sensory trigeminal system of a snake in the possession of infrared receptors.
      I. The sensory trigeminal nuclei.

PMID- 8980721
TI  - The sensory trigeminal system of a snake in the possession of infrared receptors.
      II. The central projections of the trigeminal nerve.

PMID- 8980722
TI  - Monoamine fluorescence and electron microscopic studies on small intensely
      fluorescent (granule-containing) cells in human sympathetic ganglia.

PMID- 8980723
TI  - The origin of brainstem-spinal pathways in the North American opossum (Didelphis
      virginiana). Studies using the horseradish peroxidase method.

PMID- 8980724
TI  - The organization of monoamine neurons within the brainstem of the North American
      opossum (Didelphis virginiana).

PMID- 8980725
TI  - Ocular dominance columns and their development in layer IV of the cat's visual
      cortex: a quantitative study.

PMID- 8980726
TI  - Contrast enhanced computed tomography and magnetic resonance imaging in the
      diagnosis of recurrent disc herniation.
AB  - A positive result of re-operation in patients with recurrent symptoms after
      lumbar disc surgery is likely only if a new disc herniation is present. An
      improved ability to differentiate between recurrent disc herniation and scar
      tissue by contrast enhanced CT and MRI is suggested in earlier studies. In a
      prospective study 29 patients were selected for operation for suspected recurrent
      disc herniation. The inclusion of the patients was based on clinical symptoms and
      signs and myelography or non-enhanced CT. All patients were examined by CT and
      MRI both with and without intravenous contrast pre-operatively. The examinations
      were evaluated blind on a five point scale and statistical analysed by a regret
      function. Intravenous contrast improved the diagnostic power of both CT and MRI.
      MRI was superior to CT in both non-enhanced and enhanced examinations. MRI with
      intravenous contrast enhancement is proposed as the primary examination in
      patients with suspected recurrent disc herniation.

PMID- 8980727
TI  - Primary spinal column sarcomas.
AB  - Five cases of primary spinal column sarcomas are presented. Sarcomas primarily
      originating from paravertebral soft tissues were excluded. Patients' age ranged
      from 1 to 14 years (mean 8.4 years). The male:female ration was 2:3. Two patients
      had Ewing's sarcoma (ES) originating from L5-S1 and L4-5 pedicles, respectively;
      two patients had mesenchymal chondrosarcoma (MCS) originating from L1-2 pedicles
      and L5 body, respectively; and one patient had osteogenic sarcoma (OS) of C4
      body. All patients clinically presented with pain and progressive weakness of the
      extremities. The time that elapsed between the onset of symptoms and diagnoses
      ranged from one to five months. All cases were treated with chemotherapy,
      radiotherapy and subtotal tumour resection with spinal canal decompression. Two
      cases received posterior spinal fusion operations. Three patients were alive 10
      to 98 months following diagnosis. Only the case with ES of L5-S1 pedicles was in
      complete remission and off therapy at the 98th postoperative month. The two MCS
      cases were in partial remission, and were receiving chemotherapy at the time of
      analysis. These tumours caused similar clinical findings and prognoses, and
      required combined treatment, which consisted of surgery, radiotherapy and
      chemotherapy; histologically three different types of malignant tumours are
      presented in the same category. We preferred surgical decompression and
      stabilization procedures especially for neurologically symptomatic patients, even
      if they had extensive tumours with high grades. By spinal canal decompression and
      stabilisation, we did not intend to cure the disease; however, we intended to
      provide neurological improvement, spinal stabilisation, improved quality of life,
      early mobilisation of the patient, and cytoreduction by means of surgical tumour
      ablation, which could render the chemotherapy more effective.

PMID- 8980728
TI  - Cavernomas of the central nervous system in children. A report of 22 cases.
AB  - A series of 22 patients under the age of 15 years with cavernomas were treated at
      the Section of Paediatric Neurosurgery of the Catholic University of Rome between
      1981 and 1995. The most common symptoms at presentation were epilepsy, in 12
      children, and intracranial hypertension, in 9 children; seizures were present on
      admission in 14 patients; no patient had a family history of cerebro-vascular
      malformations, two had multiple lesions. Radiological signs of significant acute
      and subacute haemorrhage were found in 17 cases. The supratentorial compartment
      was the most frequent location of the lesions, with only three subtentorial
      cavernomas. The post-surgical results were good: only four children had a
      persistence of pre-surgical neurological signs, even though they were ameliorated
      by the treatment. No patient showed a progression of pre-operative neurological
      signs, nor the onset of new deficits. Only one child died, but his clinical
      condition was critical before surgery, because of deep coma, with bilaterally
      dilated and fixed pupils, and no response to any stimulation. Our results suggest
      that the younger children present significant haemorrhage more frequently than
      the older ones; this is demonstrated by the analysis of the mean age of the
      patients with macro-haemorrhage (= 7 years) and the average age of those without
      macro-haemorrhage (= 11 years). The removal of cavernomas was always able to
      control the seizure disorders of our patients, proving that in these cases
      lesionectomy alone may be sufficient to resolve epilepsy.

PMID- 8980729
TI  - Different aspects of hearing preservation in surgery of vestibular schwannoma in
      women and men.
AB  - Pre-operative and postoperative auditory function was reviewed retrospectively in
      98 patients with vestibular schwannomas. According to their hormonal status,
      women were categorized as "premenopausal" and "postmenopausal". Before surgery,
      48% of the women (65% premenopausal) and 16% of the men presented with sudden
      hearing loss. The degree of auditory function before operation was similar for
      women and men. Preservation of pre-operative hearing was possible for 41% of the
      women (21% premenopausal) and 59% of the men. Further details of the surgery and
      the results of histopathological examination were also compared for women and
      men. Our results support substantial evidence that hearing preservation after
      surgery of vestibular schwannoma is easier to accomplish for men than for women.
      The finding of significantly more sudden hearing loss in premenopausal women may
      suggest a hormonal influence on tumour growth, which may also be partially
      responsible for the difference in hearing prognosis between women and men.

PMID- 8980730
TI  - A source of haemorrhage in adult patients with moyamoya disease: the significance
      of tributaries from the choroidal artery.
AB  - This study concerns 19 patients over 16 years of age with Moyamoya disease. Ten
      cases of intracranial haemorrhage, as the initial haemorrhagic event in patients
      aged from 21 to 55 (haemorrhagic group) and 9 cases of ischaemic events in 18- to
      53-year-old patients (ischaemic group) were included. All haemorrhages were
      associated with intraventricular haemorrhages (IVH); and all but one case of
      thalamic haemorrhage were thought to be primary IVH (2 cases of small
      paraventricular haemorrhage; 2 of small haemorrhages in the splenium; 5 with no
      intracerebral haematoma). In the 9 patients of the ischaemic group, there were 2
      cases of transient ischaemic attacks and 7 of cerebral infarction. Angiographic
      evaluations demonstrated that the abnormal basal vessel formation and the
      collateral supplies from the external carotid arteries were poorly developed in
      both groups. In contrast, the collateral circulation via the choroidal and
      posterior pericallosal arteries was well demonstrated. Furthermore, marked
      enlargement of the choroidal arteries and the medullary arteries derived from
      them was seen more frequently in the haemorrhagic group. These findings suggested
      that the haemodynamic load in the vessels supplying the walls of the posterior
      parts of the ventricles and the periventricular region was increased, especially
      in the haemorrhagic group. Those vessels were considered to be important sites of
      IVH in adult patients with Moyamoya disease.

PMID- 8980731
TI  - Characteristics of intracranial aneurysms associated with moyamoya disease. A
      review of 111 cases.
AB  - A retrospective analysis of 111 patients with aneurysms associated with Moyamoya
      disease is presented. The subjects comprised of our 12 cases and 99 other well
      documented cases. These 111 cases had 131 aneurysms. There were 48 males and 63
      females. The average age was 40.3 years. The clinical manifestations were
      intracranial haemorrhage in 99 cases (89%), and ischaemic events in 9 cases (8%),
      but no mention was made of these in the last three cases (2%). The Hunt and
      Kosnik grades were grade 1 in 8%, grade 2 in 23%, grade 3 in 31%, grade 4 in 35%,
      and grade 5 in 3%. Of the 131 aneurysms, 73 (56%) were found distributed around
      the circle of Willis, 24 (18%) in the basal ganglia, 29 (22%) on collateral
      vessels, and 5 (4%) on other vessels. Forty-six percent of the cases were treated
      surgically, 51% conservatively, and 3% by endovascular procedures. The surgical
      procedures for the aneurysms were; neck clipping in 49%, aneurysmectomy in 18%,
      wrapping of the aneurysm in 11%, coating or cautery of the aneurysm in 7%, and
      revascularization only in 11%. The outcomes were Glasgow Outcome Scale 1 in 30%,
      2 in 22%, 3 in 11%, 4 in 1%, and 5 in 25%. The main reasons for the unfavourable
      outcome were initial poor clinical grade and rebleeding. Follow-up angiography of
      25 aneurysms demonstrated that all aneurysms in the basal ganglia or on the
      collateral vessels disappeared. We recommend surgical intervention for aneurysms
      associated with Moyamoya disease to prevent rupture or rebleeding, especially for
      aneurysms around the circle of Willis. However, direct surgery is not recommended
      for aneurysms found in the basal ganglia or on the collateral vessels.

PMID- 8980732
TI  - Magnetic resonance imaging of vertebrobasilar ectasia in trigeminal neuralgia.
AB  - Vertebrobasilar ectasia is a rare cause of typical trigeminal neualgia. In a
      recently published large series only thirty-one (2%) of 1404 consecutive patients
      with vascularly determined neuralgia were found to have vertebrobasilar
      compression. We present three patients with trigeminal neuralgia caused by
      vertebrobasilar ectasia, who were evaluated with high resolution magnetic
      resonance imaging (MRI). MRI studies provided accurate information on the
      anatomical location and course of the ectatic vessel in the cerebellopontine
      angle and the caused mass effect on the brainstem. With gadolinium-enhancement
      vascular compression of the trigeminal nerve was demonstrated clearly. Surgery
      confirmed compression of the fifth nerve by an ectatic and tortuous
      vertebrobasilar artery in two cases. Following microvascular decompression
      neither patient experienced further pain. The third patient was treated with a
      ventriculoperitoneal shunt, as he developed occlusive hydrocephalus caused by the
      vertebrobasilar dolicho-ectasia. MRI is useful in the evaluation of trigeminal
      neuralgia as it excludes other aetiologies such as tumour or arteriovenous
      malformation, but also demonstrates cranial nerve compression by ectatic
      vertebral arteries.

PMID- 8980733
TI  - Chronic precentral stimulation in trigeminal neuropathic pain.
AB  - The results of Deep Brain Stimulation in deafferentation pain syndromes, in
      particular in thalamic pain, indicate that excellent long-term pain relief can
      hardly ever be achieved. We report 7 cases using Motor-Cortex-Stimulation for
      treating severe trigeminal neuropathic pain syndromes, i.e., dysaesthesia,
      anaesthesia dolorosa and postherpetic neuralgia. The first implantation of the
      stimulation device for precentral cerebral stimulation was performed in June
      1993, the last in September 1995. In all but one case the impulse-generator was
      implanted after a successful period of test stimulation. Successful means a pain
      reduction of more than 50% as assessed with a Visual Analogue Scale. Excluding
      one case, in whom a prolonged focal seizure resulting in a postictal speech
      arrest occurred during test stimulation, there have been no operative
      complications and the postoperative course was uneventful. In all the other
      patients the pain inhibition appeared below the threshold for producing motor
      effects. Initially these patients reported a good to excellent pain relief. In
      three of 6 patients a good to excellent pain control was maintained for a follow
      up period of 5 months to 2 years. In the remaining three patients the positive
      effect decreased over several months.

PMID- 8980734
TI  - Recurrent trigeminal neuralgia caused by an inserted prosthesis: report of two
      cases.
AB  - We report two cases of recurrent trigeminal neuralgia caused by an inserted
      prosthesis. Teflon material or polyurethane sponge inserted between the
      trigeminal nerve and the superior cerebellar artery became hardened and
      compressed the trigeminal nerve 17 months (Teflon) and 9 years (polyurethane
      sponge) respectively after the initial surgery. On the basis of these cases, it
      it suggested that actual decompression of the trigeminal nerve is important in
      surgery for trigeminal neuralgia, and that the prosthesis should not touch the
      trigeminal nerve.

PMID- 8980735
TI  - Spinal angiolipomas revisited: two case reports.
AB  - Approximately 60 cases of spinal angiolipomas have been described in the medical
      literature. Extradural tumours predominate. Lesions with a bony component, the
      infiltrating subgroup, were reported in 10 patients. Intradural angiolipomas were
      found three times. Several excellent review articles are available, but a
      systematic comparison of the characteristics of the two major varieties,
      infiltrating and non-infiltrating spinal extradural angiolipomas, has not so far
      been made. The authors operated on two patients with spinal angiolipomas and
      found one of them the infiltrating and the other the non-infiltrating type. Then,
      they proceeded to a review of all publish cases of infiltrating angiolipomas.
      With a knowledge of recently reported data on the subject the authors compared
      essential clinical features of both varieties of tumours. They share identical
      clinical characteristics. Differences found in age, sex or location were not
      statistically significant. Mode of onset and signs and symptoms present on
      admission were essentially similar. As could be anticipated, removal was more
      often complete in non-infiltrating tumours, but outcome was good or fair in more
      than 85% of cases in both groups. Involvement of bone by spinal angiolipomas does
      not imply a worsening in the prognosis.

PMID- 8980736
TI  - MRI-compatible titanium ventriculostomy kit: technical note.

PMID- 8980737
TI  - Polymeric controlled-release amsacrine chemotherapy in an experimental glioma
      model.
AB  - The purpose of this study was to fabricate and investigate amsacrine containing
      polymeric rods for use in interstitial chemotherapy of malignant glioma. Ethylene
      vinyl acetate copolymer (EVAc) rods containing 40% amsacrine (AMSA) were
      fabricated successfully with an extrusion method. In vitro kinetic studies
      revealed a high level of reproducibility of the production process. The release
      of AMSA showed a biphasic pattern consistent with a matrix-type controlled
      release system with an initial more rapid release rate followed by a slower and
      more linear release phase. Release of AMSA was observed for over 6 months and the
      rods continue to release in a stable fashion. In vitro studies using rat glioma
      (RG2) in cell culture showed that cells treated with AMSA released from the rods
      were killed in a dose dependent manner indicating that AMSA incorporated into the
      polymer remained biologically active. In vivo studies of rats with single AMSA
      rods implanted five days after RG2 tumour implantation revealed histological
      evidence of an anti-tumour effect as well as an increased survival (p < 0.0003).
      The mean survival of the amsacrine treated rats was 78 days with 50% still
      remaining alive > 5 months after implantation. All control animals developed
      tumours and died within 15-19 days after tumour implantation (mean = 17 days).
      Amsacrine implanted animals showed no significant histological or clinical
      evidence of toxicity. We conclude that amsacrine containing EVAc rods can be
      safely and efficaciously use against the RG2 experimental glioma in a rat model
      and warrant further investigation.

PMID- 8980739
TI  - Histological heterogeneity of neuroradiologically suspected adult low grade
      gliomas detected by Xenon enhanced computerized tomography (CT).
AB  - Xenon-enhanced computerized tomography (XeCT) was performed on 14 consecutive
      adult patients presenting with seizures showing supratentorial non-enhancing
      radiologically uniform appearing low grade gliomas on CT/MR images. Pre-operative
      XeCT patterns were compared with postoperative histological diagnosis, grading
      and Ki67 proliferation indices (PI). After gross-total, subtotal resection or
      biopsy, 11 astrocytomas, 2 oligodendrogliomas and 1 oligo-astrocytoma were
      diagnosed and graded: Grade I: 2 patients (Ki67-PI = 0.5-0.8), Grade I-II: 4
      patients (Ki67-PI = 0.3-1.5), Grade II: 3 patients (Ki67-PI = 0.5-3.5), Grade II
      III: 4 patients (Ki67-PI = 3.8-6.8) and Grade III: 1 patient (Ki67-PI = 5.2),
      (Kernohan Classification). Xenon CT studies revealed different flow patterns,
      correlating with the postoperative histological diagnosis, grading and
      proliferation indices: A tumour group with well defined, delayed, only minimally
      enhancing tumour area (5 patients, Grade I, I-II or II), a second group with less
      well defined low-flow-area borders and inhomogenous, strong enhancement within
      the tumour (4 patients, Grade II-III, III) and a third group with fast enhancing
      tumours was identified. The third pattern was exclusively shown in the 2
      oligodendrogliomas (Grade I and II-III) and 1 oligo-astrocytoma (Grade II). The
      preliminary report identifies the Xenon enhance CT as a beneficial pre-operative
      investigation for patients with radiologically uniform appearing suspected adult
      supratentorial low-grade gliomas, which may give information about the presence
      of anaplastic foci or oligodendroglial components.

PMID- 8980738
TI  - Migration of human glioma cells in response to tumour cyst fluids.
AB  - Glial tumours often show high degrees of local invasion that lead to local
      recurrence of the disease. Extracellular matrix components as well as soluble
      factors may play a critical role in this poorly understood process. Cyst fluid
      from human brain tumours may accumulate such autocrine produced factors and may
      represent a source were those factors may be easily obtained and studied. We have
      studied the effect of cyst fluids harvested from 17 glial tumours, 3 meningiomas,
      and three metastases on the motility of established human glioma cell lines. Both
      cyst fluids of high grade and low grade gliomas contained varying degrees of
      motility enhancing activity. No such activity was identified in cyst fluids
      obtained from meningiomas. The relation of mitogenic and motogenic activity in
      three selected cyst fluids was analysed using a quantitative monolayer migration
      assay. Quantitative analysis of cyst fluid effects on both proliferation and
      migration indicate that tumour cyst fluids contain factors that strongly
      stimulate cell migration and that maximum stimulation of migration did not occur
      at concentrations optimal for cell proliferation. Our findings indicate that
      glial tumours in fact produce and secrete soluble factors that may contribute to
      their dissemination in brain tissue.

PMID- 8980740
TI  - Effect of Nd:YAG laser on experimental disc degeneration. Part I. Biochemical and
      radiographical analysis.
AB  - Intervertebral disc herniation is an important health problem from both the
      social and economic aspect. It is often accompanied by a decrease in the content
      of water and proteoglycan (PG). The present study was undertaken to elucidate the
      effect of neodymium-yttrium-aluminum-garnet (Nd:YAG) laser on degenerated disc
      tissue. In this study a ventral disc herniation model in guinea pigs was
      performed to study the effects of ND:YAG laser on degenerated disc with low water
      and PG content. Effect of ND:YAG laser on degenerated cervical disc tissue is
      examined from the aspects of biochemistry and radiology. In the acute period
      water, PG, and collagen content decreased due to the ablative effect of ND:YAG
      laser on disc tissue. When changes in the degenerated disc in the post-laser
      chronic period were compared with degenerated disc findings, statistically
      significant changes could not be be found. From the results of this study, there
      is no question that the Nd:YAG laser offers many potential benefits, it remains
      to be proven whether or not this is of real benefit in the treatment of patients
      with degenerated disc disease.

PMID- 8980741
TI  - Effect of Nd:YAG laser on experimental disc degeneration. Part II. Histological
      and MR imaging findings.
AB  - The potential advantages of percutaneous procedures over traditional discectomy
      are multiple, but the use of laser energy to ablate disc tissue appears entirely
      empirical. To date, no experimental study exists investigating the results of
      laser on degenerated intervertebral disc. The present study was therefore
      undertaken to determine the histological and radiological changes induced by
      neodymium-yttrium-aluminum-garnet (Nd:YAG) laser on such disc tissue. It was
      shown that the vaporization of disc tissue was caused by Nd:YAG laser in early
      period, but this was gradually replaced by cartilaginous fibrous tissue at 60
      days after laser irradiation as a result of the proliferation of cartilaginous
      cells and fibrous tissues. Accordingly the magnetic resonance (MR) imaging index
      histogram moved to the left in the early period, but it moved to the right again
      at 60 days after laser irradiation. In view of these data, we conclude that the
      use of laser in degenerated disc disease does not represent an effective
      treatment as an alternative to conventional surgical methods.

PMID- 8980742
TI  - Infarction of a ventricular subependymoma after endoscopy: case report.

PMID- 8980743
TI  - Chronic encapsulated intracerebral haematoma.

PMID- 8980744
TI  - Intraspinal ependymal cyst.

PMID- 8980745
TI  - O-Acetyltransferases for chloramphenicol and other natural products.

PMID- 8980746
TI  - Net effect of inoculum size on antimicrobial action of ampicillin-sulbactam:
      studies using an in vitro dynamic model.
AB  - To examine the predictable effect of inoculum size on the kinetics of the
      antimicrobial action of ampicillin-sulbactam, five TEM-1 beta-lactamase-producing
      Escherichia coli strains were studied in an in vitro dynamic model at two
      different initial inocula (N0S). All bacteria were exposed to ampicillin
      sulbactam in a simulated system reflecting the pharmacokinetic profiles in human
      tissue after the administration of a single intravenous dose of ampicillin (2 g)
      plus sulbactam (1 g). Each strain was studied at low (4.0 to 5.2 log CFU/ml) and
      high (5.0 to 7.1 log CFU/ml) N0S. Despite pronounced differences in
      susceptibilities, the patterns of the killing curves observed with a given strain
      at different N0S were similar. As expected, viable bacterial counts increased
      with inoculum size. Striking visual contrasts in the respective curves for each
      organism were reflected by the area under the bacterial count-time curve (AUBC)
      but not by the difference between the N0 and the lowest bacterial counts (Nmin)
      at the nadir of the killing curve: the N0-associated changes in the AUBC on
      average were 75%, versus 2.5% for log N0--logNmin. To examine qualitative
      differences in antimicrobial effects at different N0S (i.e., the net effect of
      the inoculum), the difference in the high and low N0S was subtracted from each
      point on the killing curve obtained at the higher N0 for each strain. These
      adjusted curves were virtually superimposable on the observed killing curves
      obtained at the lower N0. Moreover, by using adjusted data, the AUBC values were
      similar at the two inocula, although slight (average, 11%) but systematic
      increases in the AUBC occurred at high N0S. Thus, there was only a weak net
      effect of inoculum size on the antibacterial effect of ampicillin-sulbactam. Due
      to similar slopes of the AUBC-log N0 plots, the antibacterial action at different
      N0S may be easily predicted by an approximate equation; the predicted AUBCs were
      unbiased and well correlated with the observed AUBCs (r = 0.997). Compiled data
      obtained with normalized AUBCs for different strains at different N0S yielded a
      positive correlation (r = 0.963) between the N0-normalized AUBC and the MIC of
      ampicillin-sulbactam. The adjustment and normalization procedure described might
      be a useful tool for revealing the net effect of the inoculum and to predict the
      inoculum effect if there are no qualitative differences in antimicrobial action
      at different inocula.

PMID- 8980747
TI  - Comparison of voriconazole (UK-109,496) and itraconazole in prevention and
      treatment of Aspergillus fumigatus endocarditis in guinea pigs.
AB  - Left-sided Aspergillus fumigatus endocarditis was established in the guinea pig
      heart by catheterization and inoculation with conidia via a tributary of the
      femoral vein. This animal model was used to compare the efficacy of the triazole
      antifungal agents voriconazole (UK-109,496) and itraconazole. In the prophylaxis
      experiments, voriconazole at a dosage of 10 mg/kg of body weight given
      intraperitoneally twice daily prevented A. fumigatus endocarditis in all but 1
      animal (11 of 12 animals were cured). Itraconazole did not prevent Aspergillus
      endocarditis when it was given at the same dosage and by the same route (0 to 12
      animals were cured). In the treatment experiments with 10 animals per group,
      voriconazole at 10, 7.5 and 5 mg/kg given orally twice daily for 7 days produced
      cure rates of 100, 70 and 0%, respectively. In contrast, itraconazole at 10 mg/kg
      given orally twice daily did not cure A. fumigatus endocarditis in the guinea
      pig. It is concluded that voriconazole is highly efficacious in the prevention
      and treatment of Aspergillus endocarditis in the guinea pig and is superior to
      itraconazole in these respects.

PMID- 8980749
TI  - Emergence of vancomycin resistance in the genus Streptococcus: characterization
      of a vanB transferable determinant in Streptococcus bovis.
AB  - Streptococcus bovis NEM760 was isolated from a stool swab collected on admission
      from a patient as surveillance for vancomycin-resistant enterococci. Strain
      NEM760 was identified as S. bovis by conventional biochemical methods and partial
      sequence analysis of its 16S rRNA. This strain was resistant to a low level of
      vancomycin (MIC, 64 micrograms/ml) but was susceptible to teicoplanin (MIC, 1
      micrograms/ml), and vancomycin induced resistance to both glycopeptides. The
      presence of a vanB-related gene in NEM760 was demonstrated in a PCR assay which
      enabled specific amplification of a 635-hp internal segment of vanB. Sequence
      analysis of the corresponding PCR product revealed that it was highly homologous
      (96% identity) to the prototype vanB sequence of Enterococcus faecalis V583. The
      VanB resistance of determinant of S. bovis NEM760 was transferred by conjugation
      to E. faecalis and Enterococcus faecium at a similar frequency of 2 x 10(-5) per
      donor. SmaI-digested genomic DNAs of independently obtained transconjugants of E.
      faecalis and E. faecium were analyzed by pulsed-field gel electrophoresis and
      Southern hybridization with a vanB DNA probe. The electrophoretic and
      hybridization patterns obtained with all transconjugants of the same species were
      indistinguishable and revealed vanB-containing chromosomal insertions of
      approximately 100 kb. These results suggest that the genes mediating VanB-type
      resistance in S. bovis NEM760 are part of large transferable genetic elements.
      The results presented in the report demonstrate for the first time the role of
      streptococci in the dissemination of vancomycin resistance among gram-positive
      bacteria.

PMID- 8980748
TI  - Therapeutic efficacy of liposomal clofazimine against Mycobacterium avium complex
      in mice depends on size of initial inoculum and duration of infection.
AB  - The therapeutic efficacy of liposomal clofazimine (L-CLF) against Mycobacterium
      avium complex (MAC) was evaluated in the acute and chronic infection models of
      the beige mouse (C57BL/6J bgj bgj). The maximum tolerated dose of L-CLF was
      inversely proportional to the infection level. L-CLF showed higher antibacterial
      activity than free clofazimine. Treatment with 25 mg of L-CLF per kg of body
      weight (intravenously) was started at days 1, 8, 15, and 22 postinfection and was
      studied at three levels of MAC infection (10(4), 10(5), and 10(6) bacilli/mouse).
      L-CLF treatment caused a significant (P < 0.05 to 0.001) reduction in the numbers
      of viable bacteria in lung, liver, and spleen at all infection levels,
      irrespective of time of treatment. However, the best results were obtained when
      an already established infection was treated (day 22). The organ-related
      differences in response to the treatment were also affected by the level of
      infection. A marked reduction in the numbers of CFU was observed in the lungs of
      mice with lower infection levels, whereas liver and spleen were treated more
      efficiently at higher infection levels. These studies might help in evaluations
      of host responses to therapy.

PMID- 8980750
TI  - T-8581, a new orally and parenterally active triazole antifungal agent: in vitro
      and in vivo evaluations.
AB  - T-8581 is a new water-soluble triazole antifungal agent. The geometric mean IC80s
      (GM-IC80S; where the IC80 is the lowest drug concentration which reduced the
      optical density at 630 nm by 80% compared with the optical density at 630 nm of
      the drug-free control) for Candida albicans were as follows: T-8581, 0.218
      microgram/ml; fluconazole; 0.148 microgram/ml; and itraconazole, 0.0170
      microgram/ml. For Cryptococcus neoformans the GM-IC80s were as follows: T-8581,
      9.28 micrograms/ml; fluconazole, 4.00 micrograms/ml; and itraconazole, 0.119
      microgram/ml. For Aspergillus fumigatus the GM-IC80s were as follows: T-8581,
      71.0 micrograms/ml; fluconazole, 239 micrograms/ml; and itraconazole, 0.379
      microgram/ml. Against systemic candidiasis in mice, the 50% effective doses
      (ED50s) of T-8581, fluconazole, and itraconazole (given orally) were 0.412,
      0.392, and > 320 mg/kg of body weight, respectively. Against systemic
      aspergillosis in mice, the ED50s of T-8581, fluconazole, and itraconazole (given
      orally) were 50.5, 138, > 320 mg/kg, respectively. T-8581 was also efficacious
      when it was given parenterally (ED50, 59.2 mg/kg), while the ED50 of fluconazole
      given parenterally was > 20 mg/kg. Against systemic aspergillosis in rabbits, T
      8581 was more effective than fluconazole and itraconazole in prolonging the life
      span. The high concentrations of T-8581 were observed in the sera of mice, rats,
      rabbits and dogs. Species differences in half-lives and areas under the
      concentration-time curves were observed, with the values for mice, rats, rabbits,
      and dogs increasing in that order. These results suggest that T-8581 would be a
      potentially effective antifungal drug for oral and parenteral use.

PMID- 8980751
TI  - Beta-lactamases and detection of beta-lactam resistance in Enterobacter spp.
AB  - Enterobacter spp. are becoming increasingly frequent nosocomial pathogens, and
      beta-lactam-resistant strains are on the increase, especially among isolates
      recovered from intensive care units. Therefore, a study was designed to
      characterize the beta-lactamases produced by 80 isolates of E. cloacae, E.
      aerogenes, E. taylorae, E. gergoviae, E. sakazakii, E. asburiae, and E.
      agglomerans by induction studies, spectrophotometric hydrolysis assays, and
      isoelectric focusing. The ability of broth microdilution and disk diffusion
      susceptibility tests to detect resistance to 16 beta-lactam antibiotics among
      these species was also assessed. All species except E. agglomerans, E. gergoviae,
      and some isolates of E. sakazakii were found to produce a Bush group 1
      cephalosporinase that was expressed inducibly or constitutively at high levels.
      In addition, some strains also produced a Bush group 2 beta-lactamase. In
      comparisons of broth microdilution and disk diffusion tests, disk diffusion tests
      failed to detect resistance in 1 of 25 isolates resistant to aztreonam and 2 of
      30 isolates resistant to ceftazidime. These results indicate that species of
      Enterobacter can possess a variety of beta-lactamases that are responsible for
      beta-lactam resistance in this genus and that the disk diffusion test may
      occasionally miss resistance in some strains.

PMID- 8980753
TI  - Once-daily gentamicin therapy for experimental Escherichia coli meningitis.
AB  - In vitro and in vivo studies have demonstrated that the bacteriologic efficacy of
      once-daily aminoglycoside therapy is equivalent to that achieved with
      conventional multiple daily dosing. The impact of once-daily dosing for
      meningitis has not been studied. Using the well-characterized rabbit meningitis
      model, we compared two regimens of the same daily dosage of gentamicin given
      either once or in three divided doses for 24 or 72 h. The initial 1 h mean
      cerebrospinal fluid (CSF) gentamicin concentration for animals receiving a single
      dose (2.9 +/- 1.7 micrograms/ml) was threefold higher than that for the animals
      receiving multiple doses. The rate of bacterial killing in the first 8 h of
      treatment was significantly greater for the animals with higher concentrations in
      their CSF (-0.21 +/- 0.19 versus -0.03 +/- 0.22 log10 CFU/ml/h), suggesting
      concentration-dependent killing. By 24h, the mean reduction in bacterial titers
      was similar for the two regimens. In animals treated for 72 h, no differences in
      bactericidal activity was noted for 24, 48, or 72 h. Gentamicin at two different
      dosages was administered intracisternally to a separate set of animals to achieve
      considerably higher CSF gentamicin concentrations. In these animals, the rate of
      bacterial clearance in the first 8 h (0.52 +/- 0.15 and 0.58 +/- 0.15 log10
      CFU/ml/h for the lower and higher dosages, respectively) was significantly
      greater than that in animals treated intravenously. In conclusion, there is
      evidence of concentration-dependent killing with gentamicin early in treatment
      for experimental E. coli meningitis, and once-daily dosing therapy appears to be
      at least as effective as multiple-dose therapy in reducing bacterial counts in
      CSF.

PMID- 8980752
TI  - IMP dehydrogenase from Pneumocystis carinii as a potential drug target.
AB  - Mycophenolic acid, a specific inhibitor of IMP dehydrogenase (IMPDH; EC
      1.1.1.205), is a potent inhibitor of Pneumocystis carinii growth in culture,
      suggesting that IMPDH may be a sensitive target for chemotherapy in this
      organism. The IMPDH gene was cloned as a first step to characterizing the enzyme
      and developing selective inhibitors. A 1.3-kb fragment containing a portion of
      the P. carinii IMPDH gene was amplified by PCR with two degenerate
      oligonucleotides based on conserved sequences in IMPDH from humans and four
      different microorganisms. Northern hybridization analysis showed the P. carinii
      IMPDH mRNA to be approximately 1.6 kb. The entire cDNA encoding P. carinii IMPDH
      was isolated and cloned. The deduced amino acid sequence of P. carinii IMPDH
      shared homology with bacterial (31 to 38%), protozoal (48 to 59%), mammalian (60
      to 62%), and fungal (62%) IMPDH enzymes. The IMPDH cDNA was expressed by using a
      T7 expression system in an IMPDH-deficient strain of Escherichia coli (strain S
      phi 1101). E. coli S phi 1101 cells containing the P. carinii IMPDH gene were
      able to grow on medium lacking guanine, implying that the protein expressed in
      vivo was functional. Extracts of these E. coli cells contained IMPDH activity
      that had an apparent Km for IMP of 21.7 +/- 0.3 microM and an apparent Km for NAD
      of 314 +/- 84 microM (mean +/- standard error of the mean; n = 3), and the
      activity was inhibited by mycophenolic acid (50% inhibitory concentration, 24
      microM; n = 2).

PMID- 8980755
TI  - Comparative activities of new fluoroquinolones, alone or in combination with
      amoxicillin, trimethoprim-sulfamethoxazole, or rifampin, against intracellular
      Listeria monocytogenes.
AB  - We studied the activities of the new fluoroquinolones clinafloxacin,
      levofloxacin, ofloxacin, and sparfloxacin alone or in combination on the
      intracellular growth of Listeria monocytogenes. Against intracellular growth of
      the four strains tested, a similar reduction of the bacterial count was obtained
      with clinafloxacin at the dose of 10 x MIC (delta log10 CFU/ml = -2.19 +/- 0.24),
      with levofloxacin at 8 x MIC (delta log10 CFU/ml = -2.28 +/- 0.25), and with
      sparfloxacin at 4 x MIC (delta log10 CFU/ml = -2.16 +/- 0.21) after 24 h of
      incubation. The combination of the quinolones with trimethoprim-sulfamethoxazole
      or amoxicillin did not show a substantial increase in activity compared to the
      fluoroquinolone alone. Antagonism with rifampin was strongly suggested. No
      modification of the MIC was observed after 20 successive infections of HeLa cells
      and contact with subinhibitory concentrations of clinafloxacin, levofloxacin, and
      sparfloxacin for 24 h. We conclude that clinafloxacin, levofloxacin, or
      sparfloxacin could represent a therapeutic alternative to amoxicillin for the
      treatment of Listeria infections in adults, especially clinafloxacin, whose MIC
      is low (0.06 to 0.12 micrograms/ml), and whose best activity against
      intracellular L. monocytogenes was obtained at a concentration of 1.2
      micrograms/ml, which is similar to clinically achievable levels. The results must
      be confirmed in an experimental model.

PMID- 8980754
TI  - Antibacterial activity in bovine lactoferrin-derived peptides.
AB  - Several peptides sharing high sequence homology with lactoferricin B (Lf-cin B)
      were generated from bovine lactoferrin (Lf) with recombinant chymosin. Two
      peptides were copurified, one identical to Lf-cin B and another differing from Lf
      cin B by the inclusion of a C-terminal alanine (lactoferricin). Two other
      peptides were copurified from chymosin-hydrolyzed Lf, one differing from Lf-cin B
      by the inclusion of C-terminal alanyl-leucine and the other being a heterodimer
      linked by a disulfide bond. These peptides were isolated in a single step from
      chymosin-hydrolyzed Lf by membrane ion-exchange chromatography and were purified
      by reverse-phase high-pressure liquid chromatography (HPLC). They were
      characterized by N-terminal Edman sequencing, mass spectrometry, and
      antibacterial activity determination. Pure lactoferricin, prepared from pepsin
      hydrolyzed Lf, was purified by standard chromatography techniques. This peptide
      was analyzed against a number of gram-positive and gram-negative bacteria before
      and after reduction of its disulfide bond or cleavage after its single methionine
      residue and was found to inhibit the growth of all the test bacteria at a
      concentration of 8 microM or less. Subfragments of lactoferricin were isolated
      from reduced and cleaved peptide by reverse-phase HPLC. Subfragment 1 (residues 1
      to 10) was active against most of the test microorganisms at concentrations of 10
      to 50 microM. Subfragment 2 (residues 11 to 26) was active against only a few
      microorganisms at concentrations up to 100 microM. These antibacterial studies
      indicate that the activity of lactoferricin is mainly, but not wholly, due to its
      N-terminal region.

PMID- 8980756
TI  - Molecular interactions of a semisynthetic glycopeptide antibiotic with D-alanyl-D
      alanine and D-alanyl-D-lactate residues.
AB  - LY191145 is an N-alkylated glycopeptide antibiotic (the p-chlorobenzyl derivative
      of LY264826) with activity against vancomycin-susceptible and -resistant
      bacteria. Similar to vancomycin, LY191145 inhibited polymerization of
      peptidoglycan when muramyl pentapeptide served as a substrate but not when
      muramyl tetrapeptide was used, signifying a substrate-dependent mechanism of
      inhibition. Examination of ligand binding affinities for LY191145 and the effects
      of this agent on R39 D,D-carboxypeptidase action showed that, similar to
      vancomycin, LY191145 had an 800-fold greater affinity for N,N'-diacetyl-L-Lys-D
      Ala-D-Ala than for N,N'-diacetyl-L-Lys-D-Ala-D-Lac. The antibacterial activity of
      LY191145 was antagonized by N,N'-diacetyl-L-Lys-D-Ala-D-Ala, but the molar excess
      required for complete suppression exceeded that needed to suppress inhibition by
      vancomycin. LY191145 is strongly dimerized and the p-chlorobenzyl side chain
      facilitates interactions with bacterial membranes. These findings are consistent
      with a mechanism of inhibition where interactions between antibiotic and D-Ala-D
      Ala or D-Ala-D-Lac residues depend on intramolecular effects occurring at the
      subcellular target site.

PMID- 8980757
TI  - Comparison of dirithromycin and penicillin for treatment of streptococcal
      pharyngitis.
AB  - In the treatment of group A beta-hemolytic streptococcal pharyngitis, penicillin
      is the drug of choice and erythromycin is the alternative. In a double-blind,
      randomized study, dirithromycin, a new macrolide, was compared with penicillin
      for the treatment of streptococcal pharyngitis. Of 121 patients who were treated
      with dirithromycin, 96.7% manifested a favorable clinical response, and of 136
      patients treated with penicillin, 94.2% manifested a favorable clinical response.
      Streptococci were eradicated from the pharynges of 85.3% of 116 dirithromycin
      treated patients and 82.5% of 126 penicillin-treated patients who returned for
      follow-up. There were no statistically significant differences in efficacy
      between the two groups. The incidence of abdominal symptoms was higher in
      dirithromycin-treated patients. Being as efficacious as penicillin and having the
      advantages over erythromycin of once-daily dosing and the lack of drug
      interactions, dirithromycin is an alternative to penicillin in the treatment of
      streptococcal pharyngitis for patients 12 years of age and older.

PMID- 8980758
TI  - Antibiotic susceptibility of the newly cultivated agent of human granulocytic
      ehrlichiosis: promising activity of quinolones and rifamycins.
AB  - Human granulocytic ehrlichiosis (HGE) is a rapidly emerging tick-borne infection
      which presents as an acute febrile illness and is associated with hematologic
      abnormalities, elevated hepatic transaminase levels, and characteristic
      intracellular organisms in peripheral blood granulocytes. Although HGE has been
      successfully treated with tetracyclines, its susceptibility to other antibiotics
      remains unknown. No clear treatment alternative exist for young children,
      pregnant women, or allergic individuals, in whom tetracyclines are contra
      indicated. We performed in vitro antibiotic susceptibility tests with this
      recently isolated agent grown in the human promyelocytic leukemia cell line HL
      60. Doxycycline (MIC, 0.25 micrograms/ml), rifampin (MIC, 0.5 micrograms/ml),
      rifabutin (MIC, < or = 0.125 micrograms/ml), ciprofloxacin and ofloxacin (both
      with MICs of 2 micrograms/ml), and trovafloxacin (MIC, < or = 0.125
      micrograms/ml) ciprofloxacin and ofloxacin (both with MICs of 2 micrograms/ml),
      and trovafloxacin (MIC, < or = 0.125 micrograms/ml) demonstrated significant
      activity against the HGE agent. These agents were also bactericidal. The HGE
      agent was resistant to clindamycin, trimethoprim-sulfamethoxazole, and imipenem
      cilastatin, as well as to ampicillin, ceftriaxone, erythromycin, and
      azithromycin, antibiotics commonly used to treat Lyme disease. Both
      chloramphenicol and gentamicin had weak inhibitory activities but were not
      bactericidal. Our findings confirm the observed clinical efficacy of doxycycline
      and further suggest that the rifamycins and quinolones, particularly
      trovafloxacin, hold promise as alternative agents for treating this new
      infection.

PMID- 8980760
TI  - A novel, double mutation in DNA gyrase A of Escherichia coli conferring
      resistance to quinolone antibiotics.
AB  - A spontaneous Escherichia coli mutant, named Q3, resistant to nalidixic acid was
      obtained from a previously described clinical isolate of E. coli, Q2, resistant
      to fluoroquinolones but susceptible to nalidixic acid (E. Cambau, F. Bordon, E.
      Collatz, and L. Gutmann, Antimicrob. Agents Chemother. 37:1247-1252, 1993). Q3
      harbored the mutation Asp82Gly in addition to the Gly81Asp mutation of Q2. The
      different mutations leading to Gly81Asp, Asp82Gly, and Gly81AspAsp82Gly were
      introduced into the gyrA gene harbored on plasmid pJSW102, and the resulting
      plasmids were introduced into E. coli KNK453 (gyrAts) by transformation. The
      presence of Asp82Gly or Gly81Asp alone led to a low-level resistance to
      fluoroquinolones but not to nalidixic acid resistance. When both mutations were
      present, resistance to both nalidixic acid and fluoroquinolones was expressed.
      Purified gyrases of the different mutants showed similar rates of supercoiling.
      Dominance of the various gyrA mutant alleles harbored on plasmids was examined.
      The susceptibility to quinolones associated with wild-type gyrA was always
      dominant. The susceptibility to nalidixic acid expressed by the Gly81Asp mutant
      was dominant, while that expressed by the Asp82Gly mutant was recessive. From
      these results, we hypothesize that some amino acids within the quinolone
      resistance-determining region of gyrase A are more important for the association
      of subunits rather than for the activity of the holoenzyme.

PMID- 8980759
TI  - Treatment of human brucellosis with doxycycline and gentamicin.
AB  - The objective of the present prospective, noncomparative, multicenter study was
      assess the safety and efficacy of gentamicin and doxycycline therapy for human
      brucellosis. In the first part of the study, a cohort of 17 patients received 100
      mg of doxycycline (or 50 mg/kg of body weight per day if the body weight was < 40
      kg) orally every 12 h for 45 days (cohort 1). In the second part of the study a
      subsequent cohort of 35 patients was treated with doxycycline at the same dosage
      for 30 days (cohort 2). All patients were treated intramuscularly with gentamicin
      at 240 mg (or 5 mg/kg per day if the body weight was < 50 kg) once daily for the
      first 7 days. Both cohorts showed a favorable response during therapy, and there
      were no therapeutic failures. Relapse was noted in 1 (5.9%; 95% confidence
      interval [95% CI], 0.15 to 28.7%) of the 17 patients in cohort 1 and in 8 (22.9%;
      95% CI, 10.4 to 40.1%) of the 35 patients in cohort 2. Nineteen patients (36.5%;
      95% CI, 23.6 to 51.0%) had adverse effects, with no differences between cohorts,
      and no patients had a treatment-limiting adverse effect. The study indicates that
      the combination of doxycycline for 45 days and gentamicin for 7 days is an
      effective and well-tolerated therapy for human brucellosis. The relapse rates
      obtained with doxycycline treatment for 30 days appear to be higher than those
      obtained with doxycycline treatment for 45 days.

PMID- 8980761
TI  - Evaluation of selected antiprotozoal drugs in the Babesia microti-hamster model.
AB  - The presently used therapy for Babesia microti infections, a combination of
      quinine and clindamycin, does not always result in parasitologic cures. To
      identify possible alternative chemotherapeutic agents for such infections, we
      screened, in the hamster-B. microti system, 12 antiprotozoal drugs that have
      either recently been released for human use or were in experimental stages of
      development at the Walter Reed Army Institute of Research for the treatment of
      malaria and leishmaniasis. Several well-recognized antimalarial drugs, such as
      mefloquine, halofantrine, artesunate, and artelenic acid, exhibited little or no
      effect on parasitemia. Two 8-aminoquinolines, WR006026 [8-(6
      diethylaminohexylamino)-6-methoxy-4-methylquinoline dihydrochloride] and WR238605
      [8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5 -(3
      trifluoromethylphenoxy-7) quinoline succinate], produced clearance of patent
      parasitemia. Furthermore, blood from infected hamsters treated with WR238605 via
      an intramuscular injection failed to infect naive hamsters on subpassage, thus
      producing a parasitologic cure. These two compounds merit further screening in
      other systems and may prove useful in treating human babesiosis.

PMID- 8980762
TI  - Synergism between tobramycin and ceftazidime against a resistant Pseudomonas
      aeruginosa strain, tested in an in vitro pharmacokinetic model.
AB  - Synergism between two antibiotics is usually tested by a checkerboard titration
      technique, or by time-kill methods. Both methods have the disadvantage that
      synergism is determined at constant concentrations of the antibiotics, which do
      not reflect reality in vivo. In the present study we determined whether synergism
      between tobramycin and ceftazidime can be found at declining concentrations below
      the MIC, and whether change in dosing sequence of the antibiotics would result in
      differences in killing. Three monotherapy and six combination therapy schedules
      were tested in an in vitro pharmacokinetic model, using a Pseudomonas aeruginosa
      resistant to both antibiotics. During all q8h dosing schedules the peak
      concentration (Cmax) was adjusted to the MIC for the strain of both antibiotics.
      During all monotherapy regimens bacterial growth was present, while all six
      combination therapy schedules showed significant killing. At t = 24 h there were
      no differences between all combination therapy schedules, but at t = 8 h the two
      combination therapy schedules with administration of tobramycin once daily showed
      a significantly faster killing. By using the area under the killing curve (AUKC)
      as a parameter for synergistic killing, simultaneous combination therapy starting
      with tobramycin once daily was significantly better than all other regimens. We
      conclude that there is synergism between tobramycin and ceftazidime at declining
      antibiotic concentrations below the MIC, resulting in a pronounced killing of a
      resistant Pseudomonas strain. Infections due to resistant Pseudomonas strains
      could possibly be treated by a synergistic combination of these drugs.

PMID- 8980763
TI  - In vitro activity of BAY 12-8039, a new fluoroquinolone.
AB  - The in vitro activity of BAY 12-8039, a new fluoroquinolone, was studied in
      comparison with those of ciprofloxacin, trovafloxacin (CP 99,219), cefpodoxime,
      and amoxicillin-clavulanate against gram-negative, gram-positive, and anaerobic
      bacteria. Its activity against mycobacteria and chlamydia was also investigated.
      BAY 12-8039 was active against members of the family Enterobacteriaceae (MIC at
      which 90% of strains tested were inhibited [MIC90S] < or = 1 microgram/ml, except
      for Serratia spp. MIC90 2 microgram/ml), Neisseria spp. (MIC90S, 0.015
      microgram/ml), Haemophilus influenzae (MIC90, 0.03 microgram/ml), and Moraxella
      catarrhalis (MIC90, 0.12 micrgram/ml), and these results were comparable to those
      obtained for ciprofloxacin and trovafloxacin. Against Pseudomonas aeruginosa, the
      quinolones were more active than the beta-lactam agents but BAY 12-8039 was less
      active than ciprofloxacin. Strains of Stenotrophomonas maltophilia were fourfold
      more susceptible to BAY 12-8039 and trovafloxacin (MIC90S, 2 micrograms/ml) than
      to ciprofloxacin. BAY 12-8039 was as active as trovafloxacin but more active than
      ciprofloxacin against Streptococcus pneumoniae (MIC90, 0.25 microgram/ml) and
      methicillin-susceptible Staphylococcus auerus (MIC90S, 0.12 micrograms/ml). The
      activity of BAY 12-8039 against methicillin-resistant S. aureus (MIC90, 2
      micrograms/ml) was lower than that against methicillin-susceptible strains. BAY
      12-8039 was active against anaerobes (MIC90S < or = 2 micrograms/ml), being three
      to fourfold more active against Bacteroides fragilis, Prevotella spp., and
      Clostridium difficile than was ciprofloxacin. Against Mycobacterium tuberculosis,
      BAY 12-8039 exhibited activity comparable to that of rifampin (MICs < or = 0.5
      micrograms/ml). Against Chlamydia trachomatis and Chlamydia pneumoniae BAY 12
      8039 was more active (MICs < or = 0.12 microgram/ml) than either ciprofloxacin or
      erythromycin and exhibited a greater lethal effect than either to these two
      agents. The protein binding of BAY 12-8039 was determined at 1 and 5
      micrograms/ml as 30 and 26.4%, respectively. The presence of human serum (at 20
      or 70%) had no marked effect on the in vitro activity of BAY 12-8039.

PMID- 8980764
TI  - Pharmacodynamic effects of antibiotics and antibiotic combinations on growing and
      nongrowing Staphylococcus epidermidis cells.
AB  - The pharmacodynamic effects of amikacin, imipenem, ofloxacin, rifampin, and
      vancomycin were studied on the slime-producing, oxacillin-resistant strain
      Staphylococcus epidermidis ATCC 35984 growing in Mueller Hinton broth or, in
      order to inhibit growth, incubated in phosphate-buffered saline. The investigated
      parameters were postantibiotic effect (PAE) and control-related effective
      regrowth time (CERT), which were determined by bioluminescence assay of bacterial
      ATP. PAE describes the delayed regrowth after drug removal, and CERT describes
      the combined effects of initial change in bacterial density during antibiotic
      exposure and delayed regrowth after drug removal. In growth cultures, PAE and
      CERT were drug concentration dependent for all antibiotics. The length of the PAE
      and CERT in the growing cultures were as follows: ofloxacin > rifampin > amikacin
      > vancomycin > imipenem. Imipenem combined with amikacin and vancomycin,
      respectively, induced a synergistic effect against growing cultures. In
      nongrowing cultures rifampin was the only drug that induced strong concentration
      dependent effects. The combination of drugs induced no synergistic effects
      against nongrowing bacteria.

PMID- 8980765
TI  - New tetracycline resistance determinants coding for ribosomal protection in
      streptococci and nucleotide sequence of tet(T) isolated from Streptococcus
      pyogenes A498.
AB  - An approach based on PCR has been developed to identify new members of the tet
      gene family in streptococci resistant to tetracycline and minocycline. Degenerate
      primers, corresponding to portions of the conserved domains of the proteins
      Tet(M), Tet(O), TeTB(P), Tet(Q), and Tet(S), all specifying the tetracycline
      minocycline resistance phenotype, were used to selectively amplify DNA fragments
      within the coding sequences. Nine streptococcal strains which do not carry the
      genes tet(M), tet(O), tetB(P), tet(Q), or tet(S) were investigated. Four of them
      gave no detectable PCR products. The five remaining strains each yielded a PCR
      product of 1.1 kbp. DNA hybridization experiments showed that these putative Tet
      determinants fell into four new hybridization classes, of which one, Tet T, was
      further analyzed. The gene tet(T) was isolated from Streptococcus pyogenes A498,
      and the nucleotide sequence that was necessary and sufficient for the expression
      of tetracycline resistance in Escherichia coli was determined. The deduced Tet(T)
      protein consists of 651 amino acids. The protein most closely related to Tet(T)
      was Tet(Q), which has 49% identical amino acid residues. A phylogenetic analysis
      revealed that Tet T represents a novel branching order among the Tet determinants
      so far described.

PMID- 8980767
TI  - Evaluation of a brain-targeting zidovudine chemical delivery system in dogs.
AB  - AIDS encephalopathy is an insidious complication of human immunodeficiency virus
      infection which is difficult to treat because of the poor uptake of many
      potentially useful antiretroviral drugs through the blood-brain barrier. A
      chemical delivery system (CDS) for zidovudine (AZT) based on redox trapping
      within the brain has been prepared and tested in several animal models to
      circumvent this limitation. The behavior of the AZT-CDS in the dog was
      considered. Parenteral administration of AZT resulted in rapid systemic
      elimination and poor uptake by the central nervous system. Ratios of the area
      under the concentration-time curve of AZT for cerebrospinal fluid to that for
      blood were 0.32, and ratios of the area under the concentration-time curve of AZT
      for brain to that for blood were approximately 0.25. Administration of an aqueous
      formulation of the AZT-CDS resulted in rapid tissue uptake and conversion of the
      CDS to the corresponding quaternary salt with the subsequent production of AZT.
      Delivered in this way, the levels of AZT in brain were 1.75- to 3.3-fold higher
      than those associated with conventional AZT administration. In addition, the
      levels of AZT in blood were 46% lower than those associated with AZT
      administration. The higher concentrations in brain and lower concentration in
      blood combined to significantly increase the ratio of the concentration of AZT in
      the brain to that in blood after AZT-CDS administration compared to that after
      AZT dosing.

PMID- 8980766
TI  - Intraperitoneal injection of tetracyclines protects mice from lethal endotoxemia
      downregulating inducible nitric oxide synthase in various organs and cytokine and
      nitrate secretion in blood.
AB  - We have tested whether tetracyclines (TETs) are able to protect mice from
      lipopolysaccharide (LPS)-induced shock, a cytokine-mediated inflammatory
      reaction. Mice, injected with a single dose of tetracycline base (TETb; 1.5, 10
      and 20 mg/kg of body weight) or doxycycline (DOXY; 1.5 mg/kg), were significantly
      protected from a lethal intraperitoneal injection of LPS (500 micrograms per
      mouse). TETs acted in early events triggered in response to LSP; in fact, they
      were no longer significantly protective if injected more than 1 h after the
      injection of endotoxin. LPS-treated mice protected by TETs showed a significant
      inhibition of tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1
      alpha), and nitrate secretion in the blood, events that were directly related
      with the survival. In mice treated with TETs a significant decrease of inducible
      nitric oxide synthase (iNOS) activity was observed in spleen and peritoneal cells
      compared with that detected in mice treated with LPS alone. Furthermore, TETs
      were found to inhibit NO synthesis by peritoneal macrophages stimulated in vitro
      with LPS. On the contrary, TETs were unable to decrease the ability of the
      macrophages to synthesize IL-1 alpha and TNF-alpha in vitro. These results
      indicate that TETs are not able to act directly on the synthesis of these
      cytokines, but they may modulate other pathways that could in turn be responsible
      for the inhibition of IL-1 alpha and TNF-alpha synthesis. Altogether, these
      results indicate that TETs are advantageous candidates for the prophylaxis and
      treatment of septic shock in mice, having both antimicrobial activity and the
      ability to inhibit endogenous TNF-alpha, IL-1 alpha, and iNOS, hence, exerting,
      potent anti-inflammatory effects.

PMID- 8980768
TI  - Variation in erythromycin and clindamycin susceptibilities of Streptococcus
      pneumoniae by four test methods.
AB  - Susceptibilities of 124 strains of Streptococcus pneumoniae to erythromycin and
      clindamycin were determined by the National Committee for the Clinical Laboratory
      Standards (NCCLS) broth microdilution method, with incubation for 20 to 24 h in
      ambient air and with modifications of this method by incubation for up to 48 h in
      air and CO2. Strains were also tested by agar dilution, E-test, and disk
      diffusion; good correlation was obtained with these methods, with clear
      separation into bimodal populations of susceptible and resistant stains. The
      broth microdilution method, however, using incubation in air for 24 h (NCCLS
      method), misclassified 4 of 92 erythromycin-resistant strains (1 as susceptible
      and 3 as intermediate) and 25 of 58 clindamycin-resistant strains (all as
      susceptible). With the exception of one strain with clindamycin, susceptible and
      resistant strains were correctly classified by the microdilution method with
      incubation in CO2 for 24 h or in ambient air for 48 h. Disk diffusion, agar
      dilution, and E-test methods with incubation in 5% CO2 are therefore reliable
      methods for susceptibility testing of pneumococci against these agents. However,
      the NCCLS microdilution method, which specifies incubation for 20 to 24 h in
      ambient air, produced significant very major errors (43%) clindamycin.
      Modification of the microdilution method by incubation in 5% CO2 or by extension
      of incubation time in ambient air to 48 h corrected these errors. Disk diffusion,
      however, was shown to be a simple, convenient, and reliable method for
      susceptibility testing of pneumococci to erythromycin and clindamycin and is
      suggested as the method of choice for these agents.

PMID- 8980769
TI  - Inhibition of metallo-beta-lactamases by a series of mercaptoacetic acid thiol
      ester derivatives.
AB  - A series of mercaptoacetic acid thiol esters have been identified as metallo-beta
      lactamase inhibitors. Electrospray mass spectrometry (ESMS) has shown that
      irreversible inhibition of the Bacillus cereus II metallo-beta-lactamase by
      SB214751, SB214752, and SB213079 was concomitant with a 90-Da increase in mass of
      the enzyme. Tryptic digestion of the B. cereus II inhibited with SB214751
      illustrated that the peptide fragment, containing the only cysteine of the
      enzyme, had undergone a mass increment of 90 Da. It was further demonstrated that
      B. cereus II hydrolyzed this type of compound across the thiol ester bond to
      yield mercaptoacetic acid. Mercaptoacetic acid is the only molecular fragment
      common to SB214751, SB214752, and SB213079, and free mercaptoacetic acid does not
      bind covalently to B. cereus II. Therefore, it is concluded that these compounds
      inhibit B. cereus II by the mechanism-based delivery of mercaptoacetic acid,
      forming a disulfide linkage with the active sites cysteine (predicted mass shift
      = +90 Da) under the aerobic conditions of the assay. The different thiol esters
      examined had a broad range of potencies against the metallo-beta-lactamases
      tested. For example SB214751, SB214752, and SB213079 all had 50% inhibitory
      concentrations of < 10 and > 1,000 microM for the Stenotrophomonas maltophilia L
      1 and Bacteroides fragilis CfiA enzymes, respectively. SB216968 was particularly
      active against the Aeromonas hydrophila CphA metallo-beta-lactamase and was found
      to be an uncompetitive inhibitor of this enzyme (Ki = 3.9 microM), whereas it
      exhibited irreversible inhibition of the L-1 enzyme. These observations with this
      series of compounds have revealed subtle differences between the active sites of
      different metallo-beta-lactamases. Finally, a novel application for isothermal
      titration calorimetry for assessing the zinc chelating activity of candidate
      inhibitors is also presented.

PMID- 8980770
TI  - Prednisolone at anti-inflammatory or immunosuppressive dosages in conjunction
      with doxycycline does not potentiate the severity of Rickettsia rickettsii
      infection in dogs.
AB  - Dogs were experimentally inoculated with Rickettsia rickettsii to determine if
      anti-inflammatory or immunosuppressive dosages of prednisolone, when administered
      in conjunction with an antirickettsial antibiotic (doxycycline), induced
      therapeutically relevant pathophysiological consequences that ultimately
      influence disease outcome. Although the duration of rickettsemia was prolonged in
      dogs receiving immunosuppressive, but not anti-inflammatory, corticosteroids,
      concurrent administration of doxycycline and corticosteroids conferred no other
      detected detrimental effects. Treatment with doxycycline or doxycycline in
      conjunction with prednisolone resulted in decreased R. rickettsii-specific
      antibody titers; however, examination of appropriately timed acute- and
      convalescent-phase serum samples would have facilitated an accurate diagnosis of
      Rocky Mountain spotted fever (RMSF) in all 16 dogs. We conclude that the
      concurrent use of anti-inflammatory or immunosuppressive doses of prednisolone in
      conjunction with doxycycline, early in the course of experimental RMSF, confers
      no clinically relevant detrimental effects and that additional studies might be
      indicated to detect possible beneficial effects in cases of severe or potentially
      fulminant RMSF. However, because the illness induced in these dogs was of mild to
      moderate severity, the results of this study should definitely not be construed
      as supporting the safety or efficacy of prednisolone for treatment of severe
      canine or human RMSF.

PMID- 8980771
TI  - MIC and time-kill studies of antipneumococcal activity of GV 118819X
      (sanfetrinem) compared with those of other agents.
AB  - Agar dilution MIC methodology was used to test the activities of GV 118819X
      (sanfetrinem), ampicillin, amoxicillin, amoxicillin-clavulanate, cefpodoxime,
      loracarbef, levofloxacin, clarithromycin, ceftriaxone, imipenem, and vancomycin
      against 53 penicillin-susceptible, 84 penicillin-intermediate and 74 penicillin
      resistant pneumococci isolated in the United States. GV 118819X was the most
      active oral beta-lactam, with MIC at which 50% of the isolates were inhibited
      (MIC50)/MIC90 values of 0.008/0.03, 0.06/0.5, and 0.5/1.0 micrograms/ml against
      penicillin-susceptible, -intermediate, and -resistant stains, respectively.
      Amoxicillin and amoxicillin in the presence of clavulanate (2:1) were the second
      most-active oral beta-lactams, followed by ampicillin and cefpodoxime; loracarbef
      was not active against penicillin-intermediate and -resistant strains.
      Clarithromycin was most active against penicillin-susceptible strains but was
      less active against intermediate and resistant stains. All pneumococcal stains
      were inhibited by ceftriaxone and imipenem at MICs of < or = 4.0 and < or = 1.0
      micrograms/ml, respectively. The activities of levofloxacin and vancomycin were
      unaffected by penicillin susceptibility. Time-kill studies of three penicillin
      susceptible, three penicillin-intermediate, and three penicillin-resistant
      pneumococci showed that all compounds, at the broth microdilution MIC, yielded
      99.9% killing of all strains after 24 h. Kinetic patterns of all oral beta
      lactams, ceftriaxone, and vancomycin were similar relative to the MIC, with 90%
      killing of all strains first observed after 12 h. However, killing by amoxicillin
      clavulanate, imipenem, and levofloxacin was slightly faster and that by
      clarithromycin was slower than that by the above-described drugs. At 2 x the MIC,
      more strains were killed earlier than was the case at the MIC, but the pattern
      seen at the MIC prevailed. When MICs and kill kinetics were combined, sanfetrinem
      was the most active oral antipneumococcal agent in this study.

PMID- 8980773
TI  - Effects of steroidal allenic phosphonic acid derivatives on the parasitic
      protists Leishmania donovani, Leishmania mexicana mexicana, and Pneumocystis
      carinii carinii.
AB  - Several pathogenic fungi and protozoa are known to have sterols distinct from
      those of their mammalian hosts. Of particular interest as targets for drug
      development are the biosyntheses of the sterols of important parasites such as
      the kinetoplastid flagellates and the AIDS-associated opportunistic protist
      Pneumocystis carinii. These pathogens synthesize sterols with an alkyl group at C
      24, and some have a double bond at C-22 of the side chain. Humans and other
      mammalian hosts are incapable of C-24 alkylation and C-22 desaturation. In the
      present study, three steroidal compounds with side chains substituted by
      phosphonyl-linked groups were synthesized and tested for their effects on
      Leishmania donovani and L. mexicana mexicana culture growth. The compounds
      inhibited organism proliferation at concentrations in micrograms per milliliter.
      The most potent inhibitors of this group of compounds were characterized by two
      ethyl groups at the phosphate function. Leishmania organisms treated with 17-[2
      (diethylphosphonato) ethylidienyl]3-methoxy-19-norpregna-1,3,5-triene exhibited
      reduced growth after transfer into inhibitor-free medium. Because there are
      currently no axenic methods available for the continuous subcultivation of P.
      carinii, the effects of these drugs on this organism were evaluated by two
      alternative screening methods. The same two diethyl phosphonosteroid compounds
      that inhibited Leishmania proliferation were also the most active against P.
      carinii as determined by the potent effect they had on reducing cellular ATP
      content. Cystic as well as trophic forms responded to the drug treatments, as
      evaluated by a dual fluorescent staining live-dead assay. Other modifications of
      steroidal phosphonates may lead to the development of related drugs with
      increased activity and specificity for the pathogens.

PMID- 8980772
TI  - The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are
      toxic to Cryptococcus neoformans by inhibition of a common target protein.
AB  - The immunosuppressant FK506 (tacrolimus) is an antifungal natural product
      macrolide that suppresses the immune system by blocking T-cell activation. In
      complex with the intracellular protein FKBP12, FK506 inhibits calcineurin, a
      Ca(2+)-calmodulin-dependent serine-threonine protein phosphatase. We recently
      reported that growth of the opportunistic fungal pathogen Cryptococcus neoformans
      is resistant to FK506 at 24 degrees C but sensitive at 37 degrees C and that
      calcineurin, the target of FKBP12-FK506, is required for growth at 37 degrees C
      in vitro and pathogenicity in vivo. These findings identify calcineurin as a
      potential antifungal drug target. In previous studies the calcineurin inhibitor
      cyclosporin A (CsA) was effective against murine pulmonary infections but
      exacerbated cryptococcal meningitis in rabbits and mice, likely because CsA does
      not cross the blood-brain barrier. Although we find that FK506 penetrates the
      CNS, FK506 also exacerbates cryptococcal meningitis in rabbits. Thus, FK506
      immunosuppression outweighs antifungal action in vivo. Like FK506, the
      nonimmunosuppressive FK506 analog L-685,818 is toxic to C. neoformans in vitro at
      37 degrees C but not at 24 degrees C, and FK506-resistant mutants are resistant
      to L-685,818, indicating a similar mechanism of action. Fluconazole-resistant C.
      neoformans clinical isolates were also found to be susceptible to both FK506 and
      L-685,818. Our findings identify calcineurin as a novel antifungal drug target
      and suggest the nonimmunosuppressive FK506 analog L-685,818 or other congeners
      warrant further consideration as antifungal drugs for C. neoformans.

PMID- 8980774
TI  - Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients
      with human immunodeficiency virus infection.
AB  - Delavirdine is a nonnucleoside reverse transcriptase inhibitor with in vitro
      activity against human immunodeficiency virus type 1 (HIV-1) that is currently
      being evaluated in combination regimens with various nucleoside analogs,
      including didanosine. Due to the pH-dependent solubility of delavirdine, the
      buffering agents in didanosine formulations may reduce delavirdine absorption. To
      evaluate the potential interaction between these agents, 12 HIV-infected patients
      (mean [+/- standard deviation] CD4+ cell count, 304 +/- 213/mm3) were enrolled in
      a three-way crossover single-dose study. Didanosine (125 to 200 mg given as
      buffered tablets) and delavirdine mesylate (400 mg) pharmacokinetics were
      evaluated when each drug was given alone (treatments A and B, respectively), when
      the two drugs were given concurrently (treatment C), and when didanosine was
      given 1 h after delavirdine (treatment D). Delavirdine exposure was reduced by
      concurrent administration of didanosine. The maximum drug concentration in serum
      (Cmax) was reduced from 7.22 +/- 4.0 to 3.51 +/- 1.9 microM, and the area under
      the concentration-time curve from 0 h to infinity (AUC0-->infinity) was reduced
      from 22.5 +/- 14 to 14 +/- 5.7 microM.h. The extent of N-dealkylation, as
      indicated by the ratio of the N-dealkylated delavirdine AUC0-->infinity to the
      delavirdine AUC0-->infinity, was unchanged across study treatments (P = 0.708).
      Reductions in didanosine exposure were observed during concurrent administration
      with delavirdine with a Cmax reduction from 4.65 +/- 2.0 to 3.22 +/- 0.59 microM
      and an AUC0-->infinity reduction from 7.93 +/- 3.9 to 6.54 +/- 2.3 microM.h.
      Thus, concurrent administration of delavirdine and didanosine may reduce the AUC0
      ->infinity of both drugs, although the clinical significance of this reduction is
      unknown. Administration of delavirdine 1 h before didanosine avoided the
      interaction. Due to the single-dose nature of this study, these findings require
      further evaluation at steady state.

PMID- 8980775
TI  - Quinolone resistance locus nfxD of Escherichia coli is a mutant allele of the
      parE gene encoding a subunit of topoisomerase IV.
AB  - The locus nfxD, which contributes to high-level quinolone resistance in
      Escherichia coli KF111b (gyrAr nfxB nfxD), is only expressed in the presence of a
      gyrA mutation, and maps to the region of the parC and parE genes, was outcrossed
      into strain KF130, creating strain DH161 (gyrAr nfxD). DNA sequence analysis of
      DH161 revealed no changes in the topoisomerase IV parC quinolone resistance
      determining region but did identify a single T-to-A mutation in parE at codon
      445, leading to a change from Leu to His. Full-length cloned parE+ partially
      complemented the resistance phenotype in KF111b and DH161, but did not complement
      the resistance phenotype in strain KF130 (gyrAr). No complementation was seen
      with cloned, truncated parE+. To confirm these findings, gyrAr was first
      outcrossed from KF130 into E. coli W3110parE10 [parE temperature sensitive(Ts)]
      and KL16. The transduced strains KL16 and W3110parE10 were subsequently
      transformed with plasmids containing cloned parE from DH161 or KL16. Cloned parE
      from DH161 increased norfloxacin resistance in the parE(Ts) background twofold at
      30 degrees C and fourfold at 42 degrees C compared to those for cloned parE from
      KL16. The same experiment with a non-Ts background revealed a twofold increase in
      the norfloxacin MIC at both 30 and 42 degrees C. These data identify the nfxD
      conditional resistance locus as a mutant allele of parE. This report is the first
      of a quinolone-resistant parE mutant and confirms the role of topoisomerase IV as
      a secondary target of norfloxacin in E. coli.

PMID- 8980776
TI  - In vitro studies of activities of the antifungal triazoles SCH56592 and
      itraconazole against Candida albicans, Cryptococcus neoformans, and other
      pathogenic yeasts.
AB  - We investigated the effects of various assay conditions on the activities of two
      antifungal drugs, SCH56592 and itraconazole, against seven species of fungi by
      the broth macrodilution testing procedure proposed by the National Committee for
      Clinical Laboratory Standards (NCCLS). For both drugs, which are insoluble in
      water, the concentration and type of solubilizing agent produced differences in
      drug activity. Starting inoculum size differences from 10(2) to 10(5) yeast cells
      per ml resulted in approximately a fourfold effect on the MIC of both drugs, but
      other significant differences were not observed with variations in synthetic
      medium composition, pH, buffering reagent, or incubation temperature. Under
      standardized conditions of reference method M27-T with 1% polyethylene glycol as
      the solubilizing agent, median MICs of SCH56592 and itraconazole of 60 and 125
      mg/ml, respectively, were demonstrated for 110 strains (12 to 23 strains for each
      of seven species). Broth microdilution results were typically severalfold higher
      than broth macrodilution results. We conclude that the NCCLS standard reference
      method can be applied without modification to the testing of SCH56592 and
      itraconazole, but particular attention to solubilizing the agents is critical to
      obtaining consistent results.

PMID- 8980777
TI  - Pharmacokinetics of aerosolized tobramycin in adult patients with cystic
      fibrosis.
AB  - This study was performed to determine the clinical pharmacokinetics of tobramycin
      in six patients with cystic fibrosis (CF) after inhalation of 600 mg. Tobramycin
      was administered with an ultrasonic nebulizer (WISTO SENIOR). Blood and urine
      were sampled until 24 h after inhalation. Maximum tobramycin levels in serum
      varied from 0.19 to 2.57 mg/liter (mean 1.27 mg/liter; standard deviation, 1.07
      mg/liter). Systemic availability (calculated from urinary output) ranged from 6.0
      to 27.4% (mean, 17.5%; standard deviation, 8.8%). The results illustrate that,
      provided that the systemic availability of tobramycin is a reflection of
      pulmonary deposition, inhalation studies with CF patients should have a
      concentration-controlled design. Furthermore, reliance on dose recommendations
      from the literature for a new patient starting on this treatment is not
      justified, but it is mandatory that deposition kinetics be studied for each
      patient and for each nebulizer. It may well be that, with higher levels of
      deposition, dosages lower than those recommended in the literature will suffice
      to obtain the desired clinical effect. In addition, the reverse may also be the
      case.

PMID- 8980778
TI  - Treatment with interleukin 12 in combination with atovaquone or clindamycin
      significantly increases survival of mice with acute toxoplasmosis.
AB  - The capacity of interleukin 12 (IL-12) to potentiate drugs in the treatment of
      murine toxoplasmosis was examined. IL-12 (100 ng/injection), atovaquone (10 mg/kg
      of body weight/day), or clindamycin (5 mg/kg/day) administered alone caused
      delayed time to death or minimal survival rates. In contrast, significant
      survival rates resulted when the same dose of IL-12 was used in combination the
      same doses of atovaquone (P=0.01) or clindamycin (P=0.001). Infected mice treated
      with IL-12 plus drug produced significantly higher levels of gamma interferon
      than controls. Although IL-12 was effective only when administered before
      infection, these results suggest that this cytokine may be a useful adjunct in
      the therapy of human toxoplasmosis in situations when cysts reactivate and
      tachyzoites start multiplying in immunocompromised patients.

PMID- 8980779
TI  - Efficacy of lasalocid against murine Pneumocystis carinii pneumonitis.
AB  - The efficacy of the ionophore lasalocid against Pneumocystis carinii pneumonitis
      in corticosteroid-immunosuppressed Sprague-Dawley rats was investigated.
      Lasalocid was effective in the prevention of the pneumonitis in a dose-dependent
      manner. At dosages of 0, 5, 10, and 20 mg/kg/day, P. carinii infection rates were
      92, 60, 20, and 0%, respectively, during dexamethasone immunosuppression. Also,
      lasalocid compared favorably with other drugs known to have anti-P. carinii
      activity, including trimethoprim-sulfamethoxazole, atovaquone, and dapsone
      trimethoprim.

PMID- 8980780
TI  - Induction of DnaK and GroEL heat shock proteins by fluoroquinolones in
      Escherichia coli.
AB  - Various fluoroquinolones (norfloxacin, enoxacin, ofloxacin, levofloxacin, and
      sparfloxacin) induce DnaK and GroEL heat shock proteins in Escherichia coli. The
      induction is transient, consistent with the kinetics of cellular DNA relaxation.
      The concentrations of fluoroquinolones required for induction are similar to
      those required for DNA relaxation and much higher than those required for cell
      death.

PMID- 8980782
TI  - Efficacies of two novel azole derivatives each containing a morpholine ring, UR
      9746 and UR-9751, against systemic murine coccidioidomycosis.
AB  - UR-9746 and UR-9751 are novel azole derivatives each containing a morpholine
      ring. They were examined for both in vitro and in vivo activities against
      Coccidioides immitis. In vitro, UR-9746 and UR-9751 were active, with MICs of 25
      and 3.1 micrograms/ml, respectively, against C. immitis Silveira; minimum
      fungicidal concentrations were > 100 micrograms/ml, the highest concentration
      tested, for both compounds. Antifungal activity in serum showed the desirable
      characteristic of remaining severalfold above the MIC at all times. Against
      systemic murine coccidioidomycosis, UR-9746 and UR-9751 prolonged survival at
      dosages of > or = 10 mg/kg/day and showed increased reduction of infectious
      burden in the spleens, livers, and lungs of treated mice with escalating dosage.
      Both compounds lacked observable toxicity and on a milligram-per-kilogram of body
      weight basis were > or = 10-fold superior to fluconazole in prolonging survival
      and clearing infection with C. immitis.

PMID- 8980781
TI  - Isolation and characterization of fluconazole- and amphotericin B-resistant
      Candida albicans from blood of two patients with leukemia.
AB  - Infections with fluconazole-resistant Candida albicans isolate have rarely been
      described in clinical settings other than oropharyngeal candidiasis in patients
      with late-stage AIDS. We report on two patients with leukemia who developed
      fungemia caused by fluconazole-resistant C. albicans after receiving fluconazole
      prophylaxis (400 mg/day) and empiric amphotericin B therapy (0.5 mg/kg of body
      weight per day). The fluconazole MICs for the isolates were > or = 64
      micrograms/ml, and the isolates were resistant to other azoles and had membrane
      sterol changes consistent with a mutation in the delta 5,6-sterol desaturase
      gene. The lack of ergosterol in the cytoplasmic membrane of the fluconazole
      resistant strains also imparted resistance to amphotericin B. Both patients were
      successfully treated with high-dose amphotericin B (1 to 1.25 mg/kg/day) and
      flucytosine (150 mg/kg/day).

PMID- 8980783
TI  - Antimicrobial activity and spectrum of LB20304, a novel fluoronaphthyridone.
AB  - Compound LB20304 is a fluoronaphthyridone carboxylic acid with a novel
      pyrrolidine substituent. This drug was compared with ciprofloxacin, levofloxacin,
      ofloxacin, and trovafloxacin against over 800 pathogens, most from blood stream
      infections, by National Committee for Clinical Laboratory Standards reference
      methods. LB20304 was the most active agent against gram-positive species
      including strains observed to be resistant to other fluoroquinolones and
      glycopeptides. The potency of LB20304 (MIC50, 0.03 micrograms/ml) against the
      Enterobacteriaceae was exceeded only by that of ciprofloxacin (0.015
      micrograms/ml). It has limited activity against gram-negative anaerobes.

PMID- 8980784
TI  - Bafilomycin A1 and intracellular multiplication of Legionella pneumophila.
AB  - Multiplication of Legionella pneumophila in HeLa cells was found to be inhibited
      by noncytotoxic concentrations of bafilomycin A1, with blockage of bacterial
      growth at a concentration 15.6 nM. The inhibiting action was evident only when
      the antibiotic was present during the initial phase of intracellular
      multiplication, i.e., during the formation of the phagosome, whereas the addition
      of the drug did not affect microorganisms already actively multiplying within the
      phagosome.

PMID- 8980785
TI  - In vitro susceptibility of Helicobacter pylori to protolichesterinic acid from
      the lichen Cetraria islandica.
AB  - With reference to the traditional use of Cetraria islandica (Iceland moss) for
      relief of gastric and duodenal ulcer, plant extracts were screened for in vitro
      activity against Helicobacter pylori. (+)-Protolichesterinic acid, an aliphatic
      alpha-methylene-gamma-lactone, was identified as an active component. The MIC
      range of protolichesterinic acid, in free as well as salt form, was 16 to 64
      micrograms/ml.

PMID- 8980787
TI  - Characterization of an inhibitor-resistant TEM (IRT) beta-lactamase in a novel
      strain of Klebsiella pneumoniae.

PMID- 8980786
TI  - Monooxygenase-like sequence of a Rhodococcus equi gene conferring increased
      resistance to rifampin by inactivating this antibiotic.
AB  - A DNA clone from Rhodococcus equi conferring low-level rifampin resistance
      through the ability to inactivate this antibiotic via its decomposition was
      identified. The iri (inactivation of rifampin) gene consisted of an open reading
      frame of 1,437 bp encoding a 479-amino-acid sequence strongly resembling those of
      monooxygenases acting upon phenolic compounds or involved in polyketide
      antibiotic synthesis. When expressed in Escherichia coli, the gene conferred
      resistance to a > 50-micrograms/ml concentration of the drug.

PMID- 8980788
TI  - The initiation of the muscle action potential.
AB  - The specific functional properties of the nicotinic acetylcholine receptors
      (AChR) and the particular oligomeric membrane organization of AChR are suggested
      to be the basis for the steep electrical depolarisation, required for the
      initiation of the postsynaptic action potentials causing muscle contraction and
      discharge of electric organs. The dimer (M(r) approximately 580,000) and the
      monomer (M(r) approximately 290,000) of the detergent-solubilized, affinity
      purified AChR of Torpedo californica electrocytes exhibit different channel
      conductances and larger oligochannels. Patch clamp data of the dimer,
      reconstituted in large lipid vesicles, show that the dimer is a double-channel
      protein causing single-channel events of conductance G(D) = 84 +/- 6 pS at 0.11 M
      K+ and 0.1 mM Ca2+ at 293 K (20 degrees C). At the same ionic conditions the
      vesicle-reconstituted monomer, if prevented from aggregation, exhibits a channel
      conductance, G(M) = 42 +/- 3 pS, which is only half of that of the dimer. The
      dimer conductivity event thus reflects the synchronous switching of its two
      constituent monomeric parts. The K(+)-conductance of the reconstituted Torpedo
      dimer is the same, and shows the same inhibitory Ca(2+)-dependence, as that of
      the Torpedo AChR expressed in Xenopus laevis oocytes (Imoto et al., Nature, 324,
      670-674, 1986). In terms of Ca(2+)-binding, reducing K(+)-transport, the
      equilibrium constant is KCa = 0.48 mM at 0.11 m K+, 20 degrees C; G0([Ca]-->0) =
      98 +/- 6 pS and G infinity ([Ca]-->infinity) = 27 +/- 6 pS. The ratio G0/G
      infinity and an estimate of the lateral surface area of the channel vestibule
      yields about 16 negatively charged groups in an average distance of 1.8 nm. These
      negative charges cause an accumulation of K+ ions in the channel vestibule by a
      factor of about 4. Our results and the comparison with the oocyte data reveal
      that it is also the dimer which is the physiological opening-closing unit of the
      AChR in the oocyte membrane. The larger macrochannel events are multiples of the
      dimer or of the monomer conductances. The occurrence of such oligochannels from
      AChR protein oligomers could guarantee the steep electrical depolarisation
      necessary to generate the action potential by the Na(+)-channel system.

PMID- 8980789
TI  - A non-cofactor role of thiamine derivatives in excitable cells?
AB  - Thiamine diphosphate (TDP) is an important cofactor of pyruvate (PDH) and alpha
      ketoglutarate (KGDH) dehydrogenases and transketolase. Thiamine deficiency leads
      to reversible and irreversible brain lesions due to impaired oxidative
      metabolism. A specific non-cofactor role for thiamine has also been proposed in
      excitable cells and thiamine triphosphate (TTP) might be involved in the
      regulation of ion channels. Thiamine is taken up by neuroblastoma cells through a
      high affinity transporter. Inside the cells, it is rapidly phosphorylated to TDP.
      This high turnover TDP pool is the precursor for TTP. Most of the TDP however has
      a low turnover and is associated with PDH and KGDH in mitochondria. In excised
      inside-out patches from neuroblastoma cells, TTP, at a concentration of 1 microM,
      activates chloride channels of large unitary conductance, the so-called maxi-Cl-
      channels. These channels are inhibited by oxythiamine from the outide. In
      addition to the role of TTP in the regulation of chloride channels, thiamine
      itself, or a presently unknown analog, may have trophic effects on neuronal
      cells.

PMID- 8980790
TI  - Determination of the chemical mechanism of neurotransmitter receptor-mediated
      reactions by rapid chemical kinetic methods.
AB  - When neurotransmitters bind to their specific receptors in the membrane of nerve
      and muscle cells they induce conformational transitions leading to the formation
      of open receptor-channels and desensitized receptor forms. A knowledge of the
      rate and equilibrium constants associated with these transitions is required to
      (i) relate the mechanism of the receptor-mediated reaction to the resulting
      changes in transmembrane voltage that trigger signal transmission between
      neurons, (ii) calculate changes in transmembrane voltage that result from the
      interaction of diverse excitatory and inhibitory receptors in the same cell, and
      (iii) understand the mechanism by which receptor function is affected by
      activators, inhibitors, including clinically important compounds, and diseases of
      the nervous system. The conformational transitions of interest occur in the
      millisecond and the sub-millisecond time region. Chemical kinetic techniques for
      studying reactions mediated by membrane-bound neurotransmitter receptors in cells
      or vesicles in this time domain were not available. Here we describe the
      development and use of a laser pulse photolysis technique suitable for chemical
      kinetic investigations of neurotransmitter receptors in the mu s and ms time
      region. The type of information that can be obtained is also discussed.

PMID- 8980791
TI  - Molecular basis of neuronal biorhythms and paroxysms.
AB  - The molecular basis of the biorhythms are evoked in relation to cerebral EEG
      rhythms and paroxysms. Basic oscillatory phenomena have been well shown and
      modeled in systems such as the glycolytic pathway, the oscillations of cAMP in
      amoebas and rhythms of the intracellular cycline during mitosis. In excitable
      cells the intracellular calcium and cAMP oscillations exhibit a signalling system
      with many advantages. Thus the question arises: to what extent can the EEG
      paroxysms observed in epileptic syndrome be due to disturbances in such basic
      molecular pathways that underlie intracellular molecular oscillations? The
      usefulness of the absence-rat-model and the implication the T type Ca(2+)-channel
      of the thalamic nuclei in the pathophysiology of this epileptic syndrome are
      discussed.

PMID- 8980792
TI  - Bronchial responsiveness of aged asthmatic patients to bronchodilator and
      methacholine.
AB  - Geriatric asthma is characterized by prolonged illness, lower remission rate,
      poor response to therapy and higher mortality rate. We studied bronchodilator
      response and methacholine challenge in 25 aged non-smoking asthmatic patients;
      thirty-two young asthmatic patients were included as control. The elderly
      patients had poorer baseline pulmonary function and were more responsive to a
      bronchodilator than the younger patients. The response to bronchoprovocation did
      not show any difference between the two groups. Our findings suggested that the
      airways of elderly asthmatics are as sensitive as those of younger patients and
      should not be under-treated.

PMID- 8980793
TI  - Allergic bronchopulmonary aspergillosis with aspergilloma mimicking fibrocavitary
      pulmonary tuberculosis.
AB  - A 47-year-old male, who presented with chronic fibrocavitary pulmonary disease,
      had received three courses of antituberculous therapy over a period of 17 years
      without relief. Four years prior to referred he had developed hemoptysis and
      rhinitis. Evaluation of the patient led to the diagnosis of allergic
      bronchopulmonary aspergillosis with coexistent aspergilloma, a rather uncommon
      association. Both his pulmonary and nasal symptoms showed a remarkable response
      to treatment with oral prednisolone. However, the possibility of concomitant
      allergic Aspergillus sinusitis remained open as the patient refused to undergo
      any invasive procedure.

PMID- 8980794
TI  - Allergen skin test and total IgE in adults with rhinitis in Singapore.
AB  - The aim of this study was to determine the allergen skin test positivity and
      total serum IgE of adult patients in Singapore with clinical features suggestive
      of allergic rhinitis. The study was carried out prospectively from January to
      August 1990. All patients had one or more of three symptoms (1) rhinorrhoea or
      nasal congestion, (2) itching nose or throat and (3) sneezing, as well as pale
      edematous nasal mucosa. Twenty inhalant allergens (Greers Laboratory, USA) were
      used for skin prick test (SPT). Serum total IgE was measured using 3M FAST test.
      Eighty-five consecutive patients, 54 males and 31 females, were studied. Their
      mean age (SD) was 26.8 (6.1) years. More than half (55.3%) had severe symptoms
      affecting work. Twenty percent did not have any positive skin reaction compared
      with 44.9% of age-matched healthy controls; 62.4% had 2 or more positive
      reactions compared to only 37.2% of controls. These differences were
      statistically significant (p < 0.002). The two most commonly, positive allergens
      were Dermatophagoides farinae (76.5%) and house dust (61.2%). No significant
      difference was found in the skin test positivity between males and females. Forty
      three patients also had serum total IgE measurement and their geometric mean IgE
      was 240 IU/I which was significantly higher than the geometric mean IgE of
      healthy controls (88 IU/I, P = 0.0005).

PMID- 8980795
TI  - A single-dose comparison of three slow-release theophylline oral preparations in
      healthy Thai volunteers.
AB  - The study was done to compare the pharmacokinetic characteristics of three slow
      release theophylline (SRT) preparations. Twelve healthy nonsmokers were randomly
      assigned a single dose of the following treatments at weekly intervals: Theo-Dur,
      Theo-24 or Xanthium orally, or aminophylline intravenously. Serially collected
      serum samples were analyzed for theophylline with use of fluorescence
      polarization immunoassay (FPIA). All three SRT preparations showed reliable
      absorption characteristics, but Theo-Dur had a shorter Tmax and MRT and a higher
      Ka. The pharmacokinetic characteristics of Theo-24 and Xanthium were similar
      except that Xanthium had lower bioavailability. Using single dose data for
      simulation of steady state pharmacokinetics, we found that a once-a-day dosage
      regimen with either Theo-24 or Xanthium would maintain serum levels within the
      therapeutic range for average non-smoking young adults whereas more frequent
      dosing intervals with Theo-Dur would be more appropriate. Our results argue
      against open substitution of SRT preparations without, close monitoring of the
      serum theophylline concentrations when a change is made.

PMID- 8980796
TI  - The cellular immune status of HBsAg-positive carriers in Malaysia.
AB  - The percentage of lymphocyte subsets from the peripheral blood of healthy adults
      and hepatitis B surface antigen (HBsAg) carriers were analyzed by flow cytometry.
      The five lymphocyte subsets studied were:- T (CD3) cells, B (CD19) cells, CD4
      cells, CD8 cells, Natural Killer (CD3- CD16+/CD56+) cells (NK cells) and the
      CD4/CD8 ratio. The percentage (mean +/- SD) for the five lymphocyte subsets from
      the healthy adults were (67.5 +/- 8.5)%, (12.4 +/- 4.5)%, (35.5 +/- 7.8)%, (36.8
      +/- 8.5)%, (17.9 +/- 8.1)% and 1.1 +/- 0.6, respectively. HBsAg carriers positive
      for HBV-DNA had a lower CD4/CD8 ratio than the healthy population (P = 0.030).
      The percentage of CD8 cells in HBsAg carriers increased significantly (r = 0.28;
      P = 0.019) with an increase in ALT levels but the values remained within normal
      range. The percentage of NK cells and CD4/CD8 ratio in HBsAg carriers positive
      for anti-HBe were higher than HBsAg carriers negative for anti-HBe (92% of which
      are HBeAg positive) (P = 0.045 and P = 0.035, respectively). The CD4/CD8 ratio in
      HBsAg carriers negative for anti-HBe (92% positive for HBeAg) was also lower than
      in the healthy population (P = 0.042). HBsAg carriers positive for HBV-DNA, HBeAg
      and raised ALT levels had a lower CD4/ CD8 ratio than did the healthy population.
      The lower ratio was due to an increase in the percentage of CD8 cells. This
      suggests an activated immune response triggered by the infection in an attempt to
      clear the virus. HBsAg carriers with normal ALT levels and who are negative for
      HBV-DNA may be in a state of tolerance.

PMID- 8980797
TI  - Multivariate analysis of prognostic factors in Philadelphia chromosome positive
      chronic myeloid leukemia: an update of the first series in Thailand.
AB  - The prognostic importance of pretreatment clinical and laboratory features was
      investigated in a group of 243 patients with Philadelphia chromosome positive
      chronic phase chronic myeloid leukemia from 1977-1995. Chemotherapy consisted of
      busulfan before 1993 or hydroxyurea after 1993. The overall median survival from
      diagnosis was 28 months. The mean age of the patients was 38 years, about 10
      years below that of Western populations. Univariate analysis identified 4 poor
      prognostic features: thrombocytopenia, more than 5% peripheral blasts, more than
      5% erythroid precursors and less than 7 g/dl of hemoglobin. The median survival
      times of patients with these 4 risk factors were 5, 11, 11 and 12 months
      respectively. Multivariate analysis only identified 2 significant prognostic
      features: thrombocytopenia and more than 5% peripheral blasts. Splenomegaly of
      more than 10 cm, basophilia and leukocytosis were associated with a shorter
      median survival but was not statistically significant. A risk scoring system was
      developed and used to classify patients into low, intermediate and high risk
      groups at 30.9%, 30.2% and 38.8% respectively. The median survival time according
      to the low, intermediate and high risk group was observed at 60, 27 and 14 months
      respectively. Prognostic factors for Thai patients with chronic myeloid leukemia
      have both similarities and differences with previously observed factors but the
      median patient survival time is shorter.

PMID- 8980798
TI  - Molecular cloning and expression of hepatitis C virus core protein and production
      of monoclonal antibodies to the recombinant protein.
AB  - The gene encoding nucleocapsid (core) protein of hepatitis C virus (HCV) was
      isolated from a Thai blood donor infected with HCV genotype 1b. The nucleotide
      sequence of this clone showed a high degree of homology to that of 4 HCV strains
      isolated from other Thai blood donors as well as that of the HCV prototypes of
      genotypes 1a, 1b, 2a and 3a. The entire region of the core gene was cloned into
      an expression plasmid pGEX-3X to be expressed as a fusion protein with
      glutathione-S-transferase (GST). E. coli transformants containing this plasmid
      did not express the fusion protein. However, GST-HCV core fusion protein could be
      produced when the core gene was truncated at the 3' end resulting in a gene
      encoding only the first 123 amino acid residues of the core protein. This fusion
      protein was insoluble in standard buffers, but could be solubilized by sarkosyl
      and thus subsequently purified using glutathione-Sepharose 4B. The purified
      fusion protein was immunogenic and could react with antibodies from blood donors
      infected with all genotypes of HCV found in Thailand. In addition, two murine
      hybridoma clones secreting monoclonal antibodies specific to the recombinant HCV
      core protein were produced. The purified HCV core protein and the monoclonal
      antibodies to the recombinant protein will be useful for developing assay systems
      for detecting anti-HCV antibodies and HCV antigen, respectively.

PMID- 8980800
TI  - Opsonophagocytosis and intracellular killing activity of neutrophils in patients
      with human immunodeficiency virus infection.
AB  - In this study, neutrophils isolated from asymptomatic HIV positive individuals,
      patients with AIDS-related complex (ARC), ARC patients receiving zidovudine (AZT)
      and full-blown AIDS patients were assayed for their opsonophagocytic and
      intracellular killing activities. Progressively decreasing opsonophagocytosis of
      C. albicans by neutrophils correlated with increasing severity of the disease in
      all groups of HIV infected individuals, as compared to neutrophils isolated from
      healthy controls. The intracellular killing of C. albicans by neutrophils of
      asymptomatic and ARC patients did not differ significantly from controls.
      Neutrophils of ARC patients receiving AZT and AIDS patients showed a slightly
      decreased killing activity in comparison to that of neutrophils from healthy
      controls.

PMID- 8980799
TI  - Production of specific monoclonal antibodies to Burkholderia pseudomallei and
      their diagnostic application.
AB  - Hybridomas secreting monoclonal antibodies (MAbs) specific to Burkholderia
      pseudomallei were produced by immunizing BALB/cJ mice with crude culture filtrate
      of B. pseudomallei. Two monoclonal antibodies were found to be highly specific to
      B.pseudomallei as tested by indirect enzyme-linked immunosorbent assay and
      immunoblotting against a panel of crude whole cell extracts from B. pseudomallei,
      B. cepacia, Pseudomonas aeruginosa, P.putida, and Escherichia coli. One of the
      specific MAbs, clone SP-M, IgM subclass, could directly agglutinate all 42 B.
      pseudomallei, isolates. The study has shown that the agglutinating MAb has
      potential for rapid identification of B. pseudomallei in primary bacterial
      culture from clinical specimens. The antibody can be used in bacteriology
      laboratories to reduce time of biochemical methods, which require a few days.

PMID- 8980801
TI  - Successful bone marrow transplantation in a Chinese boy with Wiskott-Aldrich
      syndrome.
AB  - We describe the successful use of HLA-compatible sibling bone marrow
      transplantation (BMT) in a 17-month-old Chinese boy in whom Wiskott-Aldrich
      syndrome (WAS) was diagnosed on the basis of eczema, thrombocytopenia, recurrent
      otitis media and abnormal immunological tests. The conditioning chemotherapy
      included 2 days' oral busulfan, 40 mg/m2/6 hours, and 2 days' intravenous
      cyclophosphamide, 60 mg/kg/day (BU2CY2). Complete hematological chimerism was
      achieved 3 weeks after transplantation. Eight months after his BMT the eczema has
      resolved, platelet count is normal, and he no longer has frequent infections.
      BU2CY2 as a preconditioning regimen gave complete lymphohematopoietic engraftment
      in this WAS patient with no evidence of graft-versus-host disease. The excellent
      clinical response of this patient and the inevitable fatal outcome of WAS support
      the opinion that where a histocompatible donor is available, BMT at the earliest
      opportunity is the best option. We believe this is the first case of successful
      BMT in a Chinese patient with WAS.

PMID- 8980803
TI  - Cross-protection test of an avian poxvirus isolated from houbara bustards.
AB  - An avian poxvirus was isolated previously from the houbara bustard (Chlamydotis
      undulata). We carried out a cross-protection test on 66 captive-bred canaries.
      Thirty-five canaries were vaccinated with a commercial canary poxvirus (CP)
      vaccine. Three weeks later all 66 birds were assigned randomly to six different
      groups: group Ia (n = 14) was vaccinated and challenged with houbara bustard
      poxvirus (HP) strain; group Ib (n = 13) was vaccinated and challenged with a CP
      strain; group Ic (n = 7) was vaccinated and not inoculated; group IIa (n = 14)
      was nonvaccinated and challenged with HP strain; group IIb (n = 11) was
      nonvaccinated and challenged with a CP strain; and group IIc (n = 7) was not
      vaccinated and not challenged. Vaccinated groups (Ia, Ib, Ic) had no losses and
      remained healthy. All of the birds (100%) in group IIb died within 10 days, and
      10 birds (71.4%) of group IIa died within 20 days. The nonvaccinated control
      group (IIc) remained healthy. Poxvirus was isolated from the liver, digestive
      tract, lungs, and inoculation lesions of nonvaccinated dead CP- and HP-challenged
      birds. Secondary bacterial infections were higher among nonvaccinated HP
      challenged birds (85.7%) than in nonvaccinated CP-challenged birds (25%). The
      results of this experiment reveal a degree of immunogenic relatedness between CP
      and HP strain and support the recommendation that houbara bustards be vaccinated
      with a CP vaccine.

PMID- 8980802
TI  - Insect cell-derived VP2 of infectious bursal disease virus confers protection
      against the disease in chickens.
AB  - Infectious bursal disease virus (IBDV) has become a major problem in recent
      years. Conventional vaccines make use of attenuated or inactivated viral strains,
      but these are gradually losing their effectiveness. We investigated the
      possibility of using purified VP2, a subunit of IBDV structural protein expressed
      in insect cells, as a vaccine. The VP2 gene was cloned into pAcYM1. The cloned
      gene was expressed in a baculovirus system, giving rise to a high quantity of
      recombinant VP2 (rVP2) protein. The length of the VP2 is 453 amino acids, and it
      contains two additional amino acids of the baculovirus at the carboxyl terminus.
      The molecular mass of the protein is about 48 kD. The rVP2 protein reacted with
      antibodies raised against viral VP2 and had a similar molecular weight. This
      protein was tested in a controlled vaccination experiment and compared with an
      inactivated commercial vaccine. High levels of antibodies were raised by the
      vaccinated birds. The vaccinated birds were challenged with a pathogenic viral
      strain. rVP2-vaccinated chickens exhibited high resistance to the virus. No
      mortality or weight changes in the bursa of Fabricius were observed in the
      vaccinated birds, whereas in the negative control birds, vaccinated with
      phosphate buffer, up to 50% mortality was found. Higher levels of antibodies were
      found by enzyme-linked immunosorbent assay in birds vaccinated with rVP2 compared
      with those vaccinated with the commercial vaccine. This study suggests the
      potential use of the isolated rVP2 as a subunit vaccine.

PMID- 8980804
TI  - Onset of protective immunity in chicks after vaccination with a recombinant
      herpesvirus of turkeys vaccine expressing Newcastle disease virus fusion and
      hemagglutinin-neuraminidase antigens.
AB  - The onset of protective immunity from lethal Newcastle disease virus (NDV)
      challenge of chicks was determined after vaccination with a recombinant herpes
      virus of turkeys (HVT) expressing the fusion and hemagglutinin-neuraminidase
      proteins of NDV. One-day-old specific-pathogen-free chicks devoid of maternal
      antibodies to NDV were vaccinated with 130 to 3300 plaque forming units of HVT
      (depending on the trial) and then challenged at 4, 7, 10, and 14 days
      postvaccination (DPV) with a neurotropic velogenic strain of NDV (GB Texas). The
      recombinant vaccine afforded 0%, 35-75%, 85%, and 94-100% protection when the
      vaccinated birds were challenged at 4, 7, 10, and 14 DPV, respectively. In all
      trials, challenge caused 100% mortality in unvaccinated control chicks. Newcastle
      disease virus was reisolated from the lung, liver, spleen, and brain of birds
      dying in all trials regardless of vaccine dosage or time of challenge, except
      when challenge occurred at 14 DPV.

PMID- 8980805
TI  - Comparison of the effect of different opsonins on the phagocytosis of fluorescein
      labeled staphylococcal bacteria by chicken heterophils.
AB  - Heterophil phagocytosis of fluorescein-labeled staphylococcal bacteria was
      analyzed by flow cytometry. Opsonization with two types of normal pooled sera and
      staphylococcal antisera significantly increased bacterial phagocytosis compared
      to samples without an opsonin. The staphylococcal antisera did not significantly
      increase bacterial phagocytosis compared to the normal pooled sera. Opsonization
      appears to increase bacterial phagocytosis but specific antisera may not increase
      phagocytosis beyond that caused by pooled normal sera.

PMID- 8980806
TI  - Avian Eimeria species: effect of prior or simultaneous inoculation of one species
      on cellular invasion by a second species in vivo and in vitro.
AB  - The effect of prior or simultaneous administration of Eimeria acervulina on
      cellular invasion by E. acervulina, E. tenella, or E. adenoeides was examined in
      vivo and/or in vitro. In chickens immunized with E. acervulina oocysts, invasion
      by sporozoites from a challenge inoculum of E. acervulina increased slightly over
      invasion in naive controls, and invasion by sporozoites of E. tenella and E.
      adenoeides increased by factors of 1.99 and 2.26, respectively, over that in
      controls. Conversely, simultaneous inoculation of E. acervulina along with E.
      tenella or E. adenoeides did not have a significant effect on invasion. Cultured
      baby hamster kidney cells that had been previously inoculated with E. acervulina
      sporozoites also supported significantly greater (by factors of 1.39 to 2.66)
      invasion by E. adenoeides sporozoites than did control cultures. The enhancement
      of invasion in vitro appeared to depend upon either the interval between the
      inoculation of cells with E. acervulina and E. adenoeides or the interval between
      the replating of the cells and their inoculation with E. adenoeides. There were
      no gross changes in the culture morphology between the E. acervulina-inoculated
      and noninoculated cultures. The data indicate that prior exposure to E.
      acervulina enhances invasion by other species of avian coccidia and, therefore,
      may exacerbate the infection produced by these species.

PMID- 8980807
TI  - The effect of photoperiod and nutrition on ascites incidence in broilers.
AB  - Light restriction was used to restrict growth of male broilers up to 41 days of
      age. Dietary energy and lysine were also investigated for their interaction with
      slowed growth rate. A total of 1440 male broilers was used in each of two trials.
      Light restriction significantly reduced body weights at 22 days (P < or = 0.05)
      but not at 52 days. Restricting early growth by photoperiod for the 3-to-41-day
      period reduced deaths due to ascites. Neither dietary energy nor lysine affected
      mortality from ascites. These results suggest that manipulation of photoperiod
      for young broilers is a useful way to limit early growth and subsequent ascites
      mortality.

PMID- 8980808
TI  - Evaluation of a commercial quail pox vaccine (Bio-Pox Q) for the control of
      "variant" fowl poxvirus infections.
AB  - Groups of 3-week-old specific pathogen-free chickens immunized with a commercial
      live-virus quail pox vaccine (Bio-Pox Q) were not protected against challenge
      with "variant" poxviruses isolated from chickens that were previously vaccinated
      with commercial fowl pox vaccine. The percentages of vaccinated chickens
      resistant to challenge with each of the five variant field isolates were 0%, 20%,
      0%, 20%, and 10%, respectively. However, when immunity engendered by the variant
      field isolates was challenged with the commercial quail pox vaccine virus, 80%,
      70%, 80%, 50%, and 60% of the vaccinates, respectively, were protected. Results
      from cross-immunity studies indicate that the commercial quail pox vaccine does
      share some immunologic relationship with these variant poxvirus field isolates,
      but not enough to be used in the control of some outbreaks of pox caused by
      variant poxviruses.

PMID- 8980809
TI  - Evaluation of diagnostic procedures to detect Mycoplasma synoviae in commercial
      multiplier-breeder farms and commercial hatcheries in Florida.
AB  - Sera from 5325 chickens representing 71 commercial poultry flocks were tested for
      Mycoplasma synoviae (MS) using standard National Poultry Improvement Program
      (NPIP) testing guidelines. Based on the NPIP guidelines, only sera (N = 195) from
      flocks that test positive by specific plate agglutination (SPA) were submitted
      for additional confirmatory tests. Flocks from three multihouse farms were
      identified as seropositive for MS and confirmed by culture and polymerase chain
      reaction (PCR). Serum samples (N = 195) from these seropositive flocks were
      compared by SPA, enzyme-linked immunoassay (ELISA), and hemagglutination
      inhibition (HI). Of the 195 sera tested for MS from these flocks, 145 (74%) sera
      were positive by SPA. Of the 145 SPA-positive sera, the HI test was positive for
      127 samples (90.2%), whereas the ELISA was positive for 141 samples (98.6%). This
      difference between the two tests was significant (P = 0.0006). Significant
      differences (P = 0.0002) in titer were obtained from paired serum samples that
      were submitted to three different laboratories for HI analysis. Both the SPA and
      HI tests failed to detect early infection in newly introduced flocks following
      depopulation of MS-positive facilities. Both ELISA and PCR detected new
      infections on these farms. In the MS outbreak described in this study, SPA was
      not adequate as the sole screening test and HI was not adequate for confirmation
      of flock infection status. Continued reliance on the same or a similar type of
      testing could result in missed infections. Confirmation of infection by PCR was
      preferable to HI and also may be used in place of culture. The findings of this
      study suggest that ELISA should be considered as a serologic screen in lieu of
      SPA, screening with SPA may miss MS-infected flocks, and PCR should be considered
      as a confirmatory test.

PMID- 8980810
TI  - Proximal tibiotarsal infarcts in turkeys.
AB  - Necrotic lesions in the proximal tibiotarsal bones of turkeys were evaluated by
      pathologic and bacteriologic examinations. Lesions were compatible with infarcts
      and were grossly visible as focal, gray-black, red-black, or entirely black
      triangular areas in the growth plate and proximal metaphysis at the posterior
      medial angle of the tibial head. The lesions were detected in 408 of 1000 (41%)
      tibias that were collected at seven processing plants. Histologic lesions were
      characterized by thrombosed blood vessels and a well-demarcated focal area of
      necrosis primarily in the growth plate. No inflammatory cells were present.
      Massive hemorrhage and cellular debris were common in the necrotic zone, and
      extensive, fibrin-lined clefts were often seen nearby. Staphylococci and
      Escherichia coli were frequently isolated from the lesions either in pure
      cultures or in combination with other bacteria. Histologic evidence suggests that
      the infarcts were probably traumatic in origin and that the bacterial infection
      was secondary.

PMID- 8980811
TI  - Antibody responses of chickens to inoculation with Mycoplasma gallisepticum
      membrane proteins in immunostimulating complexes.
AB  - Membrane proteins of Mycoplasma gallisepticum (MG) strain R were extracted with
      the detergent Mega-10 and incorporated into immunostimulating complexes (ISCOMs).
      A membrane protein of approximately 64 kD (p64) molecular weight was a major
      component of MG ISCOMs. Six-week-old specific-pathogen-free leghorn chickens were
      inoculated by various routes (subcutaneous; combined intranasal and eyedrop; and
      combined subcutaneous, intranasal, and eyedrop) with 10 micrograms MG proteins in
      ISCOMs, or inoculated subcutaneously with 10 micrograms MG proteins in Freund's
      adjuvant. Subcutaneous inoculation of MG ISCOMs, or MG Freund's adjuvant resulted
      in higher sero-positive rates (detected by enzyme-linked immunosorbent assay) in
      serum and respiratory tract washings, compared to combined routes of MG ISCOM
      inoculation. In chickens inoculated subcutaneously with MG ISCOMs antibodies were
      first detected at 31 days postinoculation (PI) and the sero-positive rate peaked
      at 56 days PI. Sero-positive rates started to decline at day 64 PI. In the
      Freund's adjuvant group, MG antibodies were first detected at day 21 PI, and the
      sero-positive rate peaked at day 39 PI and did not decline. MG antibodies were
      detected by ELISA in upper respiratory tract and tracheal washes from chickens
      inoculated subcutaneously with MG ISCOMs and MG Freund's adjuvant. Immunoblots to
      MG strain R whole cell proteins showed that respiratory tract washings and sera
      from chickens inoculated subcutaneously with MG ISCOMs contained immunoglobulins
      to MG proteins, with a prominent reaction to p64.

PMID- 8980812
TI  - Effect of beta-carotene, canthaxanthin, or lutein on lymphocyte proliferation (in
      vitro) of newly hatched chicks.
AB  - The aim of this study was to determine the effect of beta-carotene,
      canthaxanthin, and lutein on lymphocyte proliferation (in vitro) of newly hatched
      chicks. Tetrahydrofuran (THF) was used as the vehicle to introduce carotenoids in
      the culture media. So, we also determined effect of THF on viability of cells.
      The viabilities of fibroblast cells at 10(-3) dilution were 98% and 96% after 24
      and 48 hr of incubation. Therefore, 10(-3) (v/v) THF dilution was decided upon as
      the vehicle to introduce carotenoids in culture media. Chick bursal lymphocytes
      were incubated in the presence or absence of beta-carotene, canthaxanthin, or
      lutein and stimulated with phorbol 12, 13-dibutyrate. The results of this
      experiment suggested that THF rather than the carotenoids stimulated bursal
      lymphocyte proliferation. The mechanism by which THF acted as a mitogen is not
      known. We conclude from this study that beta-carotene, canthaxanthin, and lutein
      are not effective in enhancing in vitro bursal lymphocyte proliferation at
      concentrations of less than 10(-6) M in the presence of THF.

PMID- 8980813
TI  - DNA in situ hybridization for the rapid diagnosis of massive necrotizing avian
      adenovirus hepatitis and pancreatitis in chicks.
AB  - The present study describes the use of DNA in situ hybridization for the rapid
      diagnosis of massive necrotizing adenovirus hepatitis and pancreatitis in broiler
      chicks. A light microscope and DNA probes were used to identify avian adenovirus
      in replicate sections of formalin-fixed paraffin-embedded liver and pancreas from
      field and experimental chicks. Avian adenovirus infection was confirmed by
      transmission electron microscopy and virus isolation.

PMID- 8980815
TI  - The production of colibacillosis in turkeys following sequential exposure to
      Newcastle disease virus or Bordetella avium, avirulent hemorrhagic enteritis
      virus, and Escherichia coli.
AB  - Female large white turkeys were intranasally inoculated with either Newcastle
      disease virus (ND) or Bordetella avium (BA) at 4 weeks of age. This was followed
      by oral inoculation with an avirulent (vaccine) strain of hemorrhagic enteritis
      virus (HE) at 5 weeks and intravenous inoculation with Escherichia coli (EC) at 6
      weeks. Control birds received ND, BA, or HE followed by EC; EC alone; or nothing
      at all. Turkeys receiving one agent prior to EC challenge did not experience a
      significant increase in mortality or pericarditis. Those exposed to ND or BA
      followed by HE and EC experienced a significant elevation in mortality and
      pericarditis. A highly significant positive correlation between the number of
      infectious agents encountered during primary exposure and the incidence of
      colibacillosis after EC challenge was demonstrated.

PMID- 8980814
TI  - Antigenicity, pathogenicity, and immunogenicity of small and large plaque
      infectious bursal disease virus clones.
AB  - A serotype 1 variant strain of infectious bursal disease virus designated IN was
      passaged 40 times in BGM-70 cell line. A small plaque (SP) clone and a large
      plaque (LP) clone were then isolated and plaque purified four times. The SP and
      LP viruses formed circular plaques about 0.5 mm and 6.0 mm in diameter,
      respectively. Both clones lost their pathogenicity for specific-pathogen-free
      (SPF) chickens and did not elicit significant levels of virus-neutralizing
      antibody titers. However, the SP and LP clones maintained their immunogenicity
      when used as inactivated vaccines in SPF chickens. The restriction enzyme
      profiles of both clones were similar. Back passage of the SP and LP clones in SPF
      chickens resulted in loss of their phenotypic characteristics.

PMID- 8980816
TI  - Intratesticular inoculation of avian leukosis virus (ALV) in chickens--production
      of neutralizing antibodies and lack of virus shedding into semen.
AB  - In order to investigate the possibility of producing transgenic chickens by
      injection of avian leukosis virus-based vectors into testis, we have analyzed the
      infection rate of testicular cells following inoculation of Rous-associated virus
      type 1 (RAV-1) into the gonads of adult and 1-wk-old brown leghorn males.
      Viroproduction, neutralizing antibody production, and vital DNA presence in
      testis, blood, muscle, and semen were analyzed at various times after infection.
      Inoculation of RAV-1 into the gonads of adult males resulted in a low level of
      viroproduction in testis and blood, followed by the appearance of neutralizing
      antibody 2 or 3 wk later. Neither viroproduction in semen nor viral DNA presence
      in sperm were detected even though the infected chickens were found to produce
      RAV-1 in testis. One week after intratesticular inoculation of 1-wk-old males
      with RAV-1, a high level of viroproduction was found in blood and testis, and
      viral DNA was detected in gonadal cells. Further, by 6 wk after inoculation, the
      production of virus decreased in all tissues, viral DNA could not longer be
      detected in the testis, and neutralizing antibodies appeared in blood. All
      together these data show that it is possible to infect testicular cells by direct
      inoculation of RAV-1 in the testis, and that the immune response of both adult
      and young chickens seems to reduce this infection. Moreover, no evidence of
      spermatozoa infection was found; this result suggests that RAV-1 inoculation into
      testis may not induce genetic transmission of virus, and consequently would not
      be useful in the production of transgenic chickens.

PMID- 8980817
TI  - Intestinal colonization and organ invasion in chicks experimentally infected with
      Salmonella enteritidis phage type 4 and other phage types isolated from poultry
      in the United States.
AB  - Phage type 4 Salmonella enteritidis strains have only recently been isolated from
      poultry and humans in the United States, although this phage type predominates in
      many other countries. The present study assessed the ability of S. enteritidis
      isolates of various phage types found in the United States (including phage type
      4) to colonize the intestinal tract and invade to reach internal organs in
      experimentally infected chicks. Groups of 5-day-old single-comb white leghorn
      chicks were inoculated with a range of oral doses of three phage type 4 isolates
      and three isolates of other phage types. Although some significant differences
      were observed between individual S. enteritidis isolates in the frequencies at
      which they colonized the intestinal tracts and invaded to reach the spleens of
      inoculated chicks, no consistent overall pattern differentiated phage type 4
      isolates from isolates of other phage types.

PMID- 8980818
TI  - Experimental infection in turkeys and chickens with Ornithobacterium
      rhinotracheale.
AB  - Ornithobacterium rhinotracheale was found to cause growth retardation in both
      turkeys and chickens after experimental intra-air sac administration and to cause
      growth retardation together with airsacculitis and pneumonia after aerosol
      administration. Both turkey and chicken isolates of O. rhinotracheale were able
      to induce the same kind of respiratory inflammations and weight-gain losses in
      chickens as well as turkeys. Turkey rhinotracheitis virus was found to have a
      triggering effect on the O. rhinotracheale infection in turkeys, and Newcastle
      disease virus and to a lesser extent infectious bronchitis virus showed
      triggering effects on the O. rhinotracheale infection in chickens.
      Ornithobacterium rhinotracheale could be reisolated from affected organs of
      experimentally infected birds.

PMID- 8980819
TI  - Ornithobacterium rhinotracheale infection in turkey breeders.
AB  - A sequence of outbreaks of respiratory disease separated by intervals of about 2
      wk occurred on three turkey breeder ranches. The last two ranches affected
      belonged to different companies and were separated by a distance of 11 km.
      Mortality on the last ranch was particularly severe among certain segregated
      groups of turkeys that included toms, heavier birds, and birds undergoing a
      stressful event such as artificial insemination. On this ranch, percentages of
      mortality within an 18-day period were 5.2% in toms, 2.4% in hens, 7.4% in heavy
      toms and 5.4% in heavy hens. Turkeys from 27 to 42 wk of age were examined during
      the outbreaks. Gross lesions included severe lung consolidation with fibrinous
      exudate on the pleura and air sacs, petechiae on the epicardium, and increased
      cloudy fluid in the pericardial sac. Liver and spleen were moderately enlarged.
      Histologically, there was severe fibrinoheterophilic inflammation in the airways,
      pleura, and air sacs and severe perivascular interstitial edema in the lungs.
      Liver had acute coagulative necrosis of hepatocytes associated with occasional
      thrombosis at the periphery of the liver lobes. Ornithobacterium rhinotracheale
      was isolated from tissues of the respiratory system, such as infraorbital sinus,
      trachea, lung, and air sacs, but not from the liver, spleen, or bone marrow.
      Escherichia coli was isolated less often from lung, air sac, and trachea.

PMID- 8980820
TI  - Pathology of acute aspergillosis in turkeys.
AB  - Pathologic changes were characterized by gross examination and light microscopy
      after intra-air sac inoculation of 9- and 19-wk-old turkeys with Aspergillus
      fumigatus conidia. Turkeys were euthanatized and examined at 24, 48, 72, and 96
      hr postinoculation (PI). Lesions were largely confined to air sac membrane and
      lung tissues and were similar between the two age groups. There was progressive
      severity of gross lesions in both organs and of microscopic lesions in lung
      tissue. The character and severity of histologic lesions in air sac membranes
      were roughly similar at 24 through 96 hr PI, but there was an increasing amount
      and consolidation of exudate adherent to the epithelial surface. Lesions in air
      sac membranes included edema, heterophil and macrophage infiltrates, granulomas,
      lymphohistiocytic perivasculitis, necrosis, epithelial loss, and surface exudate.
      Discreet granulomas containing multinucleate giant cells were present at 24 hr PI
      and thereafter. Lung lesions progressed from mild interstitial pneumonia to
      extensive effacement by multifocal coalescing granulomas, necrosis, and
      hemorrhage. Severe pleuritis with local extension into lung parenchyma was seen
      at all time points. Numbers of intralesional fungal elements seen histologically
      were similar between age groups and appeared to decrease in air sac membranes and
      increase in lung tissues from 24 to 96 hr PI. Lung tissue of the 19-wk-old
      turkeys contained fewer colony-forming units per gram at time points after 24 hr
      PI.

PMID- 8980821
TI  - Capsular hyaluronic acid-mediated adhesion of Pasteurella multocida to turkey air
      sac macrophages.
AB  - Serogroup A strains of Pasteurella multocida, the major cause of fowl cholera,
      are resistant to phagocytosis in nonimmunized birds. Adherence studies with a
      capsulated strain of P. multocida (serotype A:3) and turkey air sac macrophages
      in culture showed that the bacteria were capable of adhering in large numbers to
      the macrophages but were not internalized. A noncapsulated variant of the
      bacteria (serotype -:3) showed little or no adherence and was not internalized.
      These data indicated that the adhesive properties were caused by the presence of
      a capsule on the bacteria. The role of capsular hyaluronic acid in adherence to
      macrophages was investigated. Depolymerization of the bacterial capsule with
      hyaluronidase increased phagocytosis by macrophage cultures, and addition of
      hyaluronic acid to the macrophages inhibited bacterial adherence. Additionally,
      exposure of macrophages to chondroitin sulfate B, an anionic polysaccharide
      similar to hyaluronic acid, did not affect the adhesive properties and resistance
      to phagocytosis of capsulated organisms. Treatment of macrophages with sodium
      metaperiodate or trypsin suppressed bacterial binding. Collectively, these data
      indicate that P. multocida adhesion to air sac macrophages, but not
      internalization, is mediated by capsular hyaluronic acid and suggest that
      recognition of this bacterial polysaccharide is a result of a specific
      glycoprotein receptor.

PMID- 8980822
TI  - Neonatal multifocal encephalomalacia and other lesions in the brains of Georgia
      chicks: 1991-95.
AB  - Outbreaks of neonatal multifocal encephalomalacia with sepsis have been reported
      among flocks of very young chicks in Belgium, Scotland, and the United States.
      The purposes of the present study were to describe intralesional bacterial cocci
      in chicks with this type of encephalomalacia and to determine its incidence
      during 1991-95, and to determine the importance of this lesion with respect to
      the frequency of all other brain lesions/ diseases during the same time period.
      All laboratory records of broiler chickens examined at the Georgia Poultry
      Laboratory from Jan. 1, 1991, through Dec. 31, 1995, where the histopathologic
      diagnoses included the letter string *encephal* were retrieved for further study.
      The leading etiology for brain disease was nutritional encephalomalacia (57%),
      followed by neonatal encephalomalacia (22%), septic meningoencephalitis (16%),
      and Marek's disease (14%), in turn followed by nonpurulent encephalitis (7%),
      avian encephalomyelitis (3%), and mycotic meningoencephalitis (3%). Diagnosis of
      neonatal multifocal encephalomalacia with sepsis in the brains of Georgia chicks
      is a perennial one. Microscopically, the condition is characterized by mild to
      maximal multifocal locally extensive fibrin thrombosis of blood capillaries, and
      necrosis (encephalomalacia, malacia) of surrounding zones of brain stem and/or
      cerebral hemisphere neuropile. In 44% of cases of neonatal encephalomalacia
      fibrin thrombosis of blood capillaries was accompanied by intralesional gram
      positive coccoid bacteria that were most abundant in medium- and small-sized
      arterioles or venules. Only gram-positive coccoid bacteria are found in cases of
      neonatal encephalomalacia (P < 0.05), and only gram-negative rod-shaped bacteria
      are found in cases of septic meningoencephalitis (P < 0.05). Therefore, bacterial
      culture and routine light microscopic histopathology are sufficient for
      diagnosing the condition when the differential diagnosis for neurologic disease
      in chicks includes neonatal encephalomalacia.

PMID- 8980824
TI  - Pasteurella multocida in raptors: prevalence and characterization.
AB  - Several cases dealing with Pasteurella multocida infection have been documented
      in raptors. However, the isolates have not been fully characterized nor has the
      prevalence of P. multocida in raptors been determined. Three hundred ninety-eight
      raptors were cultured for P. multocida. Results indicated that P. multocida was
      not normally carried in the pharyngeal, choanal, or cloacal regions. However, P.
      multocida was isolated from raptors with avian cholera. Isolates from eight cases
      were characterized by biotype, somatic serotype, and antibiogram. Most (six of
      eight) of the P. multocida isolates belonged to somatic serotype 1. The remaining
      two P. multocida isolates belonged to somatic serotypes 3 and 3,4. The majority
      of the isolates belonged to the subspecies multocida. All isolates were
      susceptible to penicillin G, sulfisoxazole, tetracycline, and trimethoprim
      sulfamethoxazole. Various restriction site heterogeneities of P. multocida
      chromosomal DNA were found among the raptor isolates. Results indicated that
      isolates of P. multocida somatic serotype 1 from diurnal raptors were genetically
      related.

PMID- 8980823
TI  - Pasteurella multocida in psittacines: prevalence, pathology, and characterization
      of isolates.
AB  - Although the pathogenicity of Pasteurella multocida for psittacines (parrots and
      their relatives) has been documented in several case reports, the associated
      pathologic syndromes have not been well defined nor have the isolates been
      characterized. In addition, the prevalence of P. multocida in psittacines has not
      been determined. Three hundred twenty-eight psittacines (253 clinically healthy
      and 75 clinically ill) were cultured for P. multocida. Pasteurella multocida was
      not isolated from the pharynx, choana, or cloaca of psittacines. However, in five
      dead psittacines submitted for necropsy, P. multocida was isolated. These
      isolates were characterized, and all belonged to either somatic serotype 3 or
      4,7. Pasteurella multocida somatic serotype 3 was isolated from psittacines with
      septicemia, whereas P. multocida somatic serotype 4,7 was isolated from
      psittacines with cutaneous lesions. The majority (four out of five) of the P.
      multocida isolates belonged to the subspecies multocida, and all isolates were
      susceptible to penicillin G, sulfisoxazole, gentamicin, erythromycin,
      tetracycline, and trimethoprim-sulfamethoxazole but resistant to streptomycin.
      DNA fingerprints demonstrated that isolates belonging to the same somatic
      serotype were genetically related. The isolate from a cockatiel that had been
      caught by a cat belonged to somatic serotype 3 and was not genetically related to
      the other two isolates belonging to this somatic serotype.

PMID- 8980825
TI  - The electrocardiogram of the Pekin duck.
AB  - In this study, standard limb lead electrocardiograms (ECG) were recorded in 50
      Pekin ducks. The ECG exhibited P, R, S, and T waves. A Q wave was observed in 30%
      of leads aVR aVL. All waves in lead I were of very low amplitude or almost
      isoelectric. The P wave was 20% negative, 80% positive in lead aVR and always
      positive in other leads. The duration and amplitude of P wave were 0.025 sec and
      0.17 mV, respectively, and the P-R interval was 0.06 sec in lead II. A Q wave was
      observed in 30% of leads aVR and aVL but was invisible in other leads. The
      duration of QRS complex was 0.036 sec and its amplitude was 0.069 mV. The S wave
      (rS) was greater than the R wave in leads III and aVF. The R and S waves were
      equal in lead III (66%). The mean duration and amplitude of T wave were 0.05 sec
      and 0.22 mV, respectively. The T wave was negative in leads aVR and aVL and
      positive in other leads. The Q-T interval was 0.10 sec. The mean heart rate was
      281.3 (220-375) beats/min. The average value of the mean electrical axis was +147
      degrees (+95 degrees to -160 degrees).

PMID- 8980826
TI  - Effect of ochratoxin A on Salmonella typhimurium-challenged layer chickens.
AB  - Eleven-day-old chickens received 10(8) colony-forming units Salmonella
      typhimurium orally for 2 consecutive days. The next day, the 13-day-old chickens
      were given a high dose of ochratoxin A (3 mg/kg) orally. The number of S.
      typhimurium in both the duodenal and cecal contents of chickens administered with
      high doses of ochratoxin A increased significantly when compared with control
      birds. Ochratoxin A was shown to be one of numerous factors that affect the
      susceptibility of chickens to salmonellae colonization.

PMID- 8980827
TI  - Large plasmids of avian Escherichia coli isolates.
AB  - The plasmid DNA of 30 Escherichia coli isolates from chickens was extracted and
      examined using techniques designed to isolate large plasmids. This plasmid DNA
      was examined for the presence of certain known virulence-related genes including
      cvaC, traT, and some aerobactin-related sequences. Seventeen of the 30 isolates
      contained from one to four plasmids greater than 50 kb in size. Eleven of these
      17 strains possessed plasmids greater than 100 kb in size. Therefore, E. coli
      isolates of chickens frequently contain large plasmids, and many of these
      plasmids are likely to contain virulence-related sequences.

PMID- 8980828
TI  - Restriction analysis of the MD infectious bursal disease virus strain.
AB  - The variant MD strain of infectious bursal disease virus (IBDV) was examined
      using restriction fragment length polymorphism (RFLP) and the molecular variation
      was compared with published sequences of both variant and classic IBDV strains.
      Viral RNA was transcribed into cDNA using reverse transcriptase and then
      amplified by the polymerase chain reaction (PCR). Three separate but overlapping
      fragments of 1603 bp, 1496 bp, and 1066 bp containing the entire coding region
      for VP2, VP4, and VP3, respectively, were amplified. These amplified products
      were initially cloned using the TA Cloning kit and further subcloned into the
      pGEM-3Zf and pUC19. Eight restriction enzymes, PstI, BamHI, AvaI, EcoRI, HindII,
      XmaI, SmaI, and XbaI, were tested for their ability to digest the MD PCR
      products. The resulting RFLP was analyzed and compared with the published genome
      segment A sequences of the classic IBDV strain STC and the variant IBDV strain
      GLS. Differences in restriction fragment profiles were observed after digestion
      with BamHI, EcoRI, XmaI, and SmaI, with the absence of the EcoRI site in both
      variant strains, GLS and MD. The MD PCR products lacked both XmaI and SmaI sites,
      which were present in both STC and GLS. The MD PCR products contained a BamHI
      site within the hypervariable region of VP2, which is present in STC but not in
      the variant GLS. An additional BamHI site was identified in the VP4 gene of MD
      and GLS but not in STC.

PMID- 8980829
TI  - Osteosarcoma in an American robin (Turdus migratorius).
AB  - An osteosarcoma arising from the left hemimandible was diagnosed in an adult
      American robin (Turdus migratorius). Neoplastic spindle cells were observed
      extending away from foci of trabecular bone in dense sheets, occasionally within
      osteoid tissue. The variably pleomorphic spindle cells contained fibrillar,
      lightly basophilic cytoplasm, irregular, round to ovoid nuclei, and single or
      multiple small nucleoli. This is the first report of an osseous neoplasm in a
      wild passerine.

PMID- 8980830
TI  - An occurrence of avian tuberculosis in hooded merganser (Lophodytes cucullatus).
AB  - Two imported male hooded mergansers (Lophodytes cucullatus) were introduced into
      a zoological aviary in Japan, and one of them died 10 mo later. Postmortem
      revealed numerous white yellowish nodules of various sizes in the liver. Two
      large nodules were also observed below the right lung and on the top of the left
      kidney. Histopathologically, a large number of tubercles with acid-fast bacilli
      were seen in the liver. The amyloid was deposited in the connective tissue of the
      tubercles. Bacteriologically, Mycobacterium avium serovar 1 was isolated from the
      liver.

PMID- 8980831
TI  - Isolation of paramyxovirus serotype 7 from ostriches (Struthio camelus).
AB  - Paramyxovirus serotype 7 (PMV-7) was isolated from pooled intestinal contents of
      two 5-month-old ostriches (Struthio camelus). The pathogenicity of the virus was
      comparable with lentogenic strains of Newcastle disease virus (PMV-1) in chicken
      and chicken embryo pathogenicity tests. The relationship of the virus to the
      observed pathology of proliferative nonsuppurative enteritis is unknown; the
      Campylobacter jejuni isolated was presumably the primary pathogen. To our
      knowledge, this is the first report of an isolation of PMV-7 from ostriches.

PMID- 8980832
TI  - Studies and applications of NiTi shape memory alloys in the medical field in
      China.
AB  - The biomedical study of NiTi shape memory alloys has been undertaken in China
      since 1978. A series of stimulating corrosion tests, histological observations,
      toxicity tests, carcinogenicity tests, trace nickel elements analysis and a
      number of clinical trials have been conducted. The results showed that the NiTi
      shape memory alloy is a good biomaterial with good biocompatibility and no
      obvious local tissue reaction, carcinogenesis or erosion of implants were found
      experimentally or clinically. In 1981, on the basis of fundamental studies, a
      shape memory staple was used for the first time inside the human body.
      Subsequently, various shape memory devices were designed and applied clinically
      for internal fixation of fractures, spine surgery, endoprostheses, gynaecological
      and craniofacial surgery. Since 1990, a series of internal stents have been
      developed for the management of biliary, tracheal and esophageal strictures and
      urethrostenosis as well as vascular obturator for tumour management. Several
      thousand cases have been treated and had a 1-10 year follow-up and good clinical
      results with a rather low complication rate were obtained.

PMID- 8980833
TI  - Corrosion resistance improvement of NiTi osteosynthesis staples by plasma
      polymerized tetrafluoroethylene coating.
AB  - NiTi shape Memory Alloys (SMA) are potential biomaterial candidates for medical
      devices such as osteosynthesis staples. However, Ni dissolution induced by
      uniform or localized corrosion could lead to toxicity. In this work, plasma
      polymerized tetrafluoroethylene (PPFTE) coating is used to improve the corrosion
      resistance of NiTi plates and corresponding NiTi stables. The scratch test
      indicates a good surface adhesion of the film but that it lacks cohesiveness.
      Potentiodynamic tests in physiological Hank's solution show that PPTFE coating
      improved the pitting corrosion resistance. The passivation range is increased
      from 35% to 96% compared to the untreated sample and the pit diameter is
      decreased from 100 microns to 10 microns. The uniformity of the deposited film is
      a very important parameter. When the film is damaged, the corrosion seems to
      increase in comparison to the untreated samples. Otherwise, if the staple is
      carefully manipulated, the coating follows the large deformations induced by the
      memory effect of the alloy without cracking, and then, protects efficiently the
      staple from pitting.

PMID- 8980834
TI  - The utility of superelasticity in medicine.
AB  - Nitinol alloys (Nitinol) exhibit a dramatically enhanced elasticity, known as
      "superelasticity", which is becoming integral to the design of a variety of new
      medical products. Elasticity is the most apparent of the advantages afforded by
      this material, but by no means the only or most important. Also discussed in this
      paper are features such as biocompatibility, kink resistance, constancy of
      stress, physiological compatibility, shape memory deployment, dynamic
      interference and fatigue resistance. Each of these properties is discussed and
      highlighted through example. Examples presented include stents, filters,
      retrieval baskets, and surgical tools.

PMID- 8980835
TI  - On the nature of the biocompatibility and on medical applications of NiTi shape
      memory and superelastic alloys.
AB  - Nitinol based shape memory alloys were introduced to Medicine in the late
      seventies. They possess a unique combination of properties including shape
      memory, superelasticity, great workability in the martensitic state, resistance
      to fatigue and corrosion. Despite these exceptional physical, chemical and
      mechanical properties the worldwide medical application has been hindered for a
      long time because of the lack of knowledge on the nature of the biocompatibility
      of these enriched by nickel alloys. A review of biocompatibility with an emphasis
      on the most recent studies, combined with the results of X-ray surface
      investigations, allows us to draw conclusions on the origin of the good
      biological response observed in vivo. The tendency of Nitinol surfaces to be
      covered with TiO2 oxides with only a minor amount of nickel under normal
      conditions is considered to be responsible for these positive results. A certain
      toxicity, usually observed in in vitro studies, may result from the much higher
      in vitro Ni concentrations which are probably not possible to achieve in vivo.
      The essentiality of Ni as a trace element may also contribute to the Nitinol
      biocompatibility with the human body tissues. Examples of successful medical
      applications of Nitinol utilizing shape memory and superelasticity are presented.

PMID- 8980836
TI  - Review of shape memory alloys medical applications in Russia.
AB  - In the last twenty-five years a large variety of research has been carried out in
      Russia using Shape Memory Alloys (SMA), particularly nearly equiatomic NiTi
      alloys, for medical applications. In this field of activity, Russian research
      centers have been quite successful in treating different kinds of diseases, from
      bone fractures to dental implants. This review is intended to give a panorama of
      SMA medical applications in Russia in order to illustrate the remarkable
      possibilities offered by SMA materials in the medical field.

PMID- 8980837
TI  - Innovative materials: the NiTi alloys in orthodontics.
AB  - Since ten years the NiTi alloys have gained an ever increasing place in
      orthodontic practice: that is due to their peculiar mechanical properties
      ascribed to a martensitic thermoelastic transformation which can be thermally or,
      in a proper temperature range, stress-induced. In the last case, when martensite
      is stress-induced at body temperature, the stress-strain behaviour is
      pseudoelastic with large deformations gained or recovered at constant stress,
      respectively in direct/reverse transformation: this behaviour exploited in
      orthodontics allowed to overcome the drawbacks intrinsic to the use of
      conventional alloys as stainless steel or Co-Mo alloys, where small displacements
      can be achieved at decreasing loads. From the phase state diagram of NiTi alloys
      it appears that at body temperature they are stable, but out of equilibrium:
      thermal treatments at intermediate temperatures can therefore modify the
      equilibrium state and as a consequence the transformation temperatures respect to
      body temperature. That allows to modify the recovery stress level according to
      the requirements of practice and thus disclosing new roads: the capability to
      foresee NiTi archwires pre-programmed in different sections, with a personalized
      scheme. Attention has not currently been paid to the modifications in the
      recovery stress induced by a temperature change inside the oral cavity. Recent
      results have shown that the thermal changes in the oral cavity induced by
      cold/hot liquid intake can considerably modify the stress level to which the
      dentition is exposed: though confined to the time extent connected with drinking,
      similar effects can be expected also for meals intake and should be taken into
      account for a correct procedure.

PMID- 8980838
TI  - Application of a NiTi staple in the metatarsal osteotomy.
AB  - Thirty-six metatarsal osteotomies using internal fixation of a shape memory metal
      compression staple for hallux valgus were performed in 21 women with a mean age
      of 42.3 years (30-66 years). The time for return to light work averaged 19.0
      days, and to full work and normal walk 41.2 days after the operation. Twenty
      patients (35 feet) had complete relief from pain. Only in one foot, the pain was
      transferred under the second metatarsal head. The appearance of the feet was
      apparently improved and the width of the forefeet was decreased by a mean of 0.90
      cm after the operation. Radiographic analysis of feet showed that all osteotomies
      united, and the average angle of hallux valgus was improved from 31.2 degrees to
      16.3 degrees and the mean intermetatarsal angle from 12.0 degrees to 6.4 degrees.
      No external fixation of plaster splintage was needed and the distal fragment
      during healing of the osteotomy was stable. The time of bone healing was
      shortened and patients were allowed to bear weight at an early time.

PMID- 8980839
TI  - Recent advances and some problems in the delineation of epileptic syndromes in
      children.
AB  - The current International Classification of Epilepsies and Epileptic Syndromes
      has classified a number of age-related epileptic syndromes in children, but some
      of these entities have not been well delineated and many syndromes not included
      in the International Classification have been proposed. This article is intended
      to supplement some of the currently listed childhood epileptic syndromes, discuss
      certain problems with the classification system, and review some of the proposed
      pediatric syndromes.

PMID- 8980840
TI  - Febrile seizures--treatment and outcome.
AB  - Assessment of treatment strategies in febrile seizures should be based on short-
      and long-term outcomes, with and without acute, intermittent, or chronic medical
      intervention, as well as short- and long-term side effects. Febrile seizures are
      a benign condition with a normal neurological, motor, intellectual, and cognitive
      long-term outcome and have a low risk of later epilepsy in most cases. Even many
      complex febrile seizures have a benign outcome. Prophylaxis may or may not reduce
      the recurrence rate, but does not appear to improve the long-term outcome as
      compared to acute treatment of seizures in progress. All agree that chronic
      prophylaxis with anti-epileptic agents is justified only in highly selected
      cases, if at all. Treatment with benzodiazepines during febrile episodes appears
      to effectively reduce the recurrence rate, provided adequate doses are given and
      compliance problems minimized. A selective approach to intermittent diazepam
      prophylaxis seems rational, as the recurrence risk and response to treatment are
      highly variable. An attractive alternative is acute treatment at seizure onset
      with rectal diazepam in solution given by the parents at home in order to prevent
      prolonged recurrent seizures. This regimen has the potential of moving the first
      line of anti-convulsant defence close to the child. It appears to be effective,
      inexpensive, feasible even for non-professionals, has few side effects and is
      well accepted by the parents. A reasonable policy would be to treat simple
      febrile seizures solely with acute rectal diazepam in solution and reserve
      intermittent diazepam prophylaxis for selected cases including those with
      multiple or prolonged recurrences, several risk factors for recurrent febrile
      seizures and other special situations.

PMID- 8980841
TI  - Adrenocorticotropic hormone and vigabatrin treatment of children with infantile
      spasms underlying cerebral palsy.
AB  - Nine infants with an underlying static encephalopathy (confirmed as cerebral
      palsy in a later follow-up examination) and newly diagnosed infantile spasms were
      entered in an open study with adrenocorticotropic hormone (ACTH) and vigabatrin
      as the initial therapy regimen. The ACTH was discontinued after 4-6 weeks and the
      infants were maintained on vigabatrin alone. Following an initial response with
      complete suppression of spasms in all patients, a long term response maintained
      for a mean of 19.2 months was confirmed in all but one child. Tolerability
      appeared excellent with 7 of 9 patients reporting no side effects; vigabatrin
      related hypotonia presented in all patients and turned out to be a 'positive'
      side-effect on the abnormally increased muscle tone of these infants. Given the
      very poor prognosis of infantile spasms especially in such conditions as cerebral
      palsy, the combination of ACTH and vigabatrin appears to be an interesting
      therapy advance with very few side effects.

PMID- 8980842
TI  - Coefficient of variation of R-R intervals in severe brain damage.
AB  - The coefficient of variation of R-R intervals (CVRR) was studied in 18 children
      having severe brain damage with a mean +/- standard deviation (s.d.) age of 8.4
      +/- 5.9 years, who were divided into ten patients complicated with respiratory
      insufficiency (RI group) and eight patients with severe athetotic cerebral palsy
      (SA group). CVRR was obtained in the resting supine position, and was compared
      with that in 22 neurologically normal controls. CVRR in the RI group (mean +/-
      S.D., 2.19 +/- 1.28%) was significantly lower than that in controls (5.56 +/-
      1.53%), while CVRR in the SA group (11.30 +/- 3.91%) was significantly higher
      than that in controls (both P < 0.01, ANOVA). In particular, the four patients
      with brain death showed extremely low CVRR of 1.00-1.29%. Since CVRR was 4.09% in
      the patient aged 4 years with birth injury of the upper cervical spinal cord
      causing absence of spontaneous respiration, the extremely low CVRR in patients
      with brain death may be directly related to brainstem dysfunction. The cause of
      the high CVRR in the SA group was not determined. Thus, CVRR may be useful for
      quantitative evaluation of severe neurological disorder.

PMID- 8980843
TI  - West syndrome: individualized ACTH therapy.
AB  - Individualized ACTH treatment of the West syndrome (WS) was assessed in a
      prospective multicenter study, in which each patient's dosage was increased
      stepwise according to response. Our series included six patients with cryptogenic
      and 24 with symptomatic infantile spasms. During the treatment period the total
      ACTH dose ranged from 58 to 373 i.u./kg. In the cryptogenic group one patient
      responded to pre-ACTH pyridoxine and four to the lowest dosage of ACTH (3 i.u./kg
      daily) with cessation of spasms and good outcome; one patient needed the highest
      dosage (12 i.u./kg daily) for cessation of seizures and became developmentally
      retarded. In the symptomatic group, 21 of the 24 patients needed 6-12 i.u./kg
      daily; 12 became seizure-free or having infrequent non-IS fits. Complications
      such as arterial hypertension, cerebral ventricle dilatation, cardiac
      hypertrophy, and prolonged adrenocortical hyporesponsiveness were related to the
      dose. The individualization provides all the benefits of ACTH treatment with
      minimal side effects and cost.

PMID- 8980845
TI  - West syndrome: individualized ACTH therapy, by Heiskala et al.

PMID- 8980844
TI  - Serial magnetic resonance imaging in children with postinfectious encephalitis.
AB  - We analyzed follow-up magnetic resonance images (MRI) in eight children with
      clinical postinfectious encephalitis (PIE), and discussed their pathogeneses.
      Three categories of MRI findings were apparent: (1) multifocal lesions in the
      white matter with/without basal ganglia involvement consistent with acute
      disseminated encephalomyelitis (ADEM) (three patients); (2) single or multifocal
      lesions localized only in the gray matter (two patients); and (3) localized
      lesions in the brain stem, basal ganglia or cerebellum. Some lesions in the
      patients in Categories 1 and 2 migrated or were resolved quickly, sometimes
      within 10 days. Gadolinium caused linear or spotty enhancement in the patients in
      Category 2. These findings suggest that Categories 1 and 2 are a self-limiting
      allergic angiopathy without demyelination. In contrast, the lesions in the
      patients in Category 3 were fixed, and not resolved within 6 months (three
      patients). The pathogenesis of Category 3 is not known. All except one patient
      had no prednisolone (PSL) therapy, however; all lesions were resolved completely
      or markedly reduced in size, which indicates PSL therapy is not always necessary
      in patients with PIE.

PMID- 8980846
TI  - Comment on the ACTH treatment of the West syndrome.

PMID- 8980847
TI  - Practical guidelines for physicians in the management of febrile seizures.
AB  - Recent studies have shown that adequate medication can prevent the recurrence of
      febrile seizures (FS). It has also been clarified that the vast majority of,
      though not all, FS patients follow a benign course. Then, questions arise as to
      whether or not FS should be prevented, particularly in light of the risks of side
      effects from drugs. Which kinds of FS can be prevented, if necessary? The
      guidelines presented here are aimed primarily at helping general practitioners in
      considering how to manage FS most appropriately. The guidelines stress that
      judgements should be individualized, while referring to a few specific 'warning
      factors'. The guidelines follow a 'laissez-faire' principle for the majority of
      FS cases, whereas intermittent therapy with diazepam and continuous medication
      with either phenobarbital or valproate are indicated in other limited cases
      meeting respective definite criteria.

PMID- 8980848
TI  - Report on the activity of child neurology in Malaysia.

PMID- 8980849
TI  - Afferent and efferent connections of the lateral and medial pallia of the silver
      lamprey.
AB  - Injections of the carbocyanine dye, DiI, into the lateral pallium of the silver
      lamprey reveal that this pallial region receives bilateral inputs from the
      olfactory bulbs, dorsomedial telencephalic neuropil, and the habenular nuclei,
      and ipsilateral inputs from the septum, preoptic area, medial pallium, thalamus,
      and, possibly, the striatum. The efferent projections of the lateral pallium form
      dorsal (olfacto-habenular tract of Heier) and ventral (olfacto-thalamic and
      hypothalamic tracts of Heier) bundles. The dorsal bundle terminates ipsilaterally
      in the dorsal pallium, medial pallium, habenular nuclei, and pretectum and
      contralaterally in the habenular nuclei and, possibly, the dorsal pallium. The
      ventral bundle terminates ipsilaterally in the septum, striatum, and preoptic
      areas and bilaterally within the hypothalamus. Injections of DiI into the medial
      pallium reveal bilateral inputs to this pallial formation from the olfactory
      bulbs, the dorsomedial telencephalic neuropil, septum, habenular nuclei, thalamic
      nuclei, preoptic area and hypothalamus, as well as ipsilateral inputs from the
      lateral pallium, dorsal isthmal grey and midbrain tegmentum. The efferent
      projections of the medial pallium form dorsal, ventral and descending bundles.
      The dorsal bundle terminates ipsilaterally in the dorsal and lateral pallia and
      in the olfactory bulb. The ventral bundle terminates ipsilaterally in the dorsal
      pallium and bilaterally within the lateral pallium and in preoptic and
      hypothalamic areas. The descending bundle terminates bilaterally in thalamic and
      hypothalamic areas and in the pretectum and optic tectum. These data support a
      number of earlier hypotheses concerning pallial homologues in lampreys and other
      vertebrates but suggest that the earlier hypothesis of an olfactory origin of the
      telencephalon of craniates should be rejected.

PMID- 8980850
TI  - The forebrain of the blind cave fish Astyanax hubbsi (Characidae). I. General
      anatomy of the telencephalon.
AB  - This paper presents a survey of the cell groups in the telencephalon of the
      teleost Astyanax hubbsi, based on series of transverse sections stained with the
      Nissl-Kluver-Barrera and Bodian procedures. The work was conducted for two
      reasons. Firstly, it was intended to determine the contribution of the forebrain
      of blind cave fish to certain forms of behavior. An understanding of the anatomy
      of the telencephalic organization is essential for such a neuroethological
      approach. The second purpose was to provide the cytoarchitectural basis for the
      experimental analysis of the fiber connectivity of the telencephalon of A.
      hubbsi. Furthermore, information about the forebrain of characids is widely
      lacking, and this study may thus provide important knowledge about the cellular
      organization of characid forebrains for comparative anatomists. The brain of A.
      hubbsi is slender and elongated. Both optic nerves and optic tectum are reduced.
      Three longitudinal sulci-s. ypsiliformis, s. externus and s. limitans
      telencephali-can be distinguished in the telencephalon. A fiber lamina reaching
      from the s. externus to the s. limitans telencephali separates the area dorsalis
      (D) from the area ventralis telencephali (V). The two hemispheres are connected
      by fibers decussating in the anterior commissure. Although cross sections
      revealed no distinct fiber laminae between cytoarchitectonic components, 17 cell
      masses could be delineated: ten of these belong to D, seven to V. The topological
      analysis yielded the following results. The dorsal telencephalon D consists of
      three longitudinal columns, termed pars medialis (Dm), pars dorsalis and
      centralis (Dd and Dc) considered together, and par lateralis (Dl), which converge
      into a uniform posterior part (Dp). The columns can be divided into several
      subregions: Dm1 and Dm2, as well as Dlv and Dld, precommissurally, Dm3 and Dm4
      postcommisurally. At polus posterior levels nucleus tenia can be identified. The
      ventral telencephalon (V) is arranged precommissurally in a periventricular
      neuronal column consisting of a dorsal (Vd) and ventral (Vv) part. Additionally,
      a lateral part (VI) is delineated. More caudally, a supracommissural part (Vs), a
      commissural part (Vc), a posterior part (Vp), and nucleus entopeduncularis are
      identified. This topological organization reflects many features characteristic
      for actinopterygian forebrains.

PMID- 8980851
TI  - The forebrain of the blind cave fish Astyanax hubbsi (Characidae). II.
      Projections of the olfactory bulb.
AB  - The primary subdivisions of the telencephalon of a characidian, Astyanax hubbsi,
      were extensively described and this subsequent study elucidates the organization
      of the secondary olfactory system based on horseradish peroxidase (HRP) and
      carbocyanine dye (DiI) tracing techniques. Both methods yielded similar results.
      Two fiber bundles project from the olfactory bulbs into the ventral rostral
      telencephalon: the medial olfactory tract (tom), embedded in the white matter of
      the ventral telencephalon (V), which gives rise to a dorsal (tom-d) and a ventral
      (tom-v) branch, and the lateral olfactory tract (tol). Running caudally, fibers
      of the tom-v synapse both ipsi- and contralaterally, after decussation in the
      ventral part of the anterior commissure, identified as the interbulbar commissure
      of Goldstein, in the medial terminal field of V, and in the preoptic terminal
      field. The dorsal branch (tom-d) projects bilaterally to a complex pattern of
      terminal fields, including the medial terminal field in V, the central terminal
      field in the dorsomedial forebrain (Dm), the caudal part of the lateral terminal
      field in the dorsoposterior telencephalon (Dp), and, finally, a hypothalamic
      terminal field at the lateral edge of the posterior nucleus tuberis. In addition,
      some fibers of tom-d and tom-v reach into the contralateral olfactory bulb. Here,
      both nerve terminals and cells were stained in the olfactory nucleus. The lateral
      olfactory tract (tol) runs along the lateral edge of the external sulcus forming
      a horizontal band. Extensive terminals were identified bilaterally in the lateral
      terminal field, which uniformly covers the medial and caudal parts of the dorsal
      hemispheres (Dc, Dl and Dp). Fibers decussate prominently in the dorsal part of
      the anterior commissure. A small number of projections, which join the stria
      medullaris, protrude into the diencephalon, decussate in the habenular
      commissure, and turn rostrally back into the telencephalon to synapse in the
      caudal part of the contralateral terminal field. These features resemble a simple
      bauplan of olfactory fiber connections in actinopterygian brains and further
      indicate that substantial parts of the telencephalon are not dominated by
      olfactory inputs.

PMID- 8980852
TI  - Sensitivity and behavioral responses to the pheromone androstenone are not
      mediated by the vomeronasal organ in domestic pigs.
AB  - Based largely on results of studies of laboratory rodents, the vomeronasal or
      accessory olfactory system is believed to function mainly in social
      communication, mediating the effects of stimuli such as urine or glandular
      secretions on the behavior or endocrine response of conspecifics. In the domestic
      pig (Sus scrofa), the steroid androstenone has been identified as a pheromone
      that facilitates expression of both attraction to the male and a receptive mating
      stance in estrous females. Though the domestic pig is one of the few vertebrate
      species in which the identity of a compound that functions as a pheromone is
      known, the role of the vomeronasal system in domestic pigs has never been
      investigated. We have examined the role of the vomeronasal organ in mediating the
      pheromonal effects of androstenone in pigs. In addition, we have examined the
      structure of the vomeronasal organ at the gross and light-microscopic levels. The
      vomeronasal organ appears functional, with sensory epithelium lining the medial
      wall, and has access to stimuli from both the oral and nasal cavities. To
      determine whether the vomeronasal organ is necessary for androstenone detection
      or attraction or receptive behavior in female pigs, access to the vomeronasal
      organ was blocked with surgical cement, and androstenone detection threshold and
      sexual behavior were measured. Experimental animals did not differ significantly
      in androstenone sensitivity, measured behaviorally, from untreated controls.
      Vomeronasal organ-blocked animals also did not differ from untreated controls in
      either androstenone-mediated receptive standing behavior or attraction to the
      odor of androstenone. We conclude that in the domestic pig, the vomeronasal organ
      is not necessary for androstenone detection or androstenone-mediated sexual
      behavior in estrous females.

PMID- 8980853
TI  - Visual system dysfunction in migraine: a review of clinical and psychophysical
      findings.
AB  - This paper reviews both clinical and experimental literature relating to visual
      dysfunction in migraine, starting with the eye and progressing via the retina and
      visual pathways to the visual cortex. Migraine is associated with (i) a pupillary
      sympathetic hypofunction, and (ii) a cortical hypersensitivity to visual stimuli
      (perhaps only in migraine with aura), the pathogenesis of which remains to be
      determined. Various hypotheses are discussed, and it is proposed that the methods
      of visual psychophysics may represent a useful approach in the future study of
      cortical hyperexcitability in migraine. Paradoxically, little research has been
      directed towards understanding (i) the photophobia of migraine attacks, and (ii)
      how migraine may be triggered by visual stimuli. Research aimed at elucidating
      the mechanisms of these phenomena may enhance understanding of the pathogenesis
      of migraine.

PMID- 8980854
TI  - A sixth-century Irish headache cure and its use in a south German monastery.
AB  - Medieval headache treatment is largely unknown. Medieval incantations against
      headache enumerate bodily organs to be protected. One 8th-century Latin hymn from
      Lake Constance using this device is addressed to St. Aid "mechprech", who has
      been identified as Aed Mac Bricc, Bishop of Killare, 6th century. This Irish
      Saint inspired unusual legends by some rather unorthodox activities: He abducted
      a young girl as hostage while his inheritance was withheld, but at the same time
      was seen surrounded by angels. He prayed for a nun who was pregnant and made the
      pregnancy vanish by a miracle, and he replaced the severed heads of maids, men
      and horses, creating a new spring as a by-product of this operation. Already at
      his birth his head had hit a stone, leaving a hole in the stone which collected
      rainwater that cured all ailments. In our own time, such "bullaun stones" are
      still believed to cure headache in Ireland. According to the legends collected by
      Plummer and Colgan, St. Aed Mac Bricc was well known for his power to cure
      headaches. He relieved St. Brigid's headache when she was suffering many miles
      away, but his most impressive cure was in convincing a headache sufferer that the
      patient's headache could actually be transferred own head. The headache hymn or
      incantation is intended to repeat Aed's unique miracle.

PMID- 8980855
TI  - Brain MRI in children with migraine: a controlled morphometric study.
AB  - Sixteen children and adolescents, aged 5-17 years, with migraine and 24 migraine
      free age-matched healthy volunteers underwent brain MRI (1.0 T). Signal
      intensities of the brain, midsagittal and coronal diameters of the brainstem were
      quantitatively measured. General signal intensities did not differ between the
      groups. Compared to controls (17%), more migraine patients (50%) had high-signal
      foci on T2-weighted images. The diameters of the pons were greater in the
      migraine group (p = 0.016), although within the normal range. The diameters of
      the mesencephalon and the medulla oblongata did not differ between the groups,
      perhaps because they reach the adult size in early childhood in contrast to the
      pons, which continues to grow. Childhood migraine may be associated with slightly
      more than average growth of the pons. As the pathophysiology of migraine is still
      unclear, it might be worth studying with new MR methods.

PMID- 8980856
TI  - An epidemiologic study of headache among children and adolescents of southern
      Brazil.
AB  - To study the epidemiology of pediatric headache, we conducted a cross-sectional
      study of a randomized and proportional sample of 538 male and female students, 10
      to 18 years old. They were in the 5th to 8th grade of the schools of Porto
      Alegre, RS, Brazil. The headache disorders were classified on the basis of
      clinical interview as well as a physical and neurological examination using the
      operational diagnostic criteria of the International Headache Society (IHS). The
      following headache prevalences were found: lifetime, 93.2%; last year, 82.9%;
      last week, 31.4%; last 24 h, 8.9%. Last week and last 24 h headache complaints
      were twice as prevalent in the female group. During the last year the prevalence
      of headache disorders was 72.8% for tension-type and 9.9% for migraine headache
      and was not associated with age distribution. Only the last year and last week
      prevalences of tension-type headache were significantly higher in the female
      group. The last year prevalence of headache disorders proved to be positively
      associated with sex and age variables. The prevalence of headache disorders was
      found to be extremely high in this population group, requiring more attention on
      the part of investigators as a public health problem.

PMID- 8980857
TI  - Histamine inhalation is a specific but insensitive laboratory test for migraine.
AB  - Migraine is a subjective complaint and no laboratory test has until now been of
      value. The aim of the present study is to evaluate whether histamine inhalation
      may be used as a diagnostic test for migraine. In a double-blind study design, 15
      migraineurs and 15 control subjects scored headache intensity and characteristics
      before, during, and in the subsequent 12 h after inhalation of increasing doses
      of histamine (0, 2, 4, 8, 16, 32 and 64 mg/ml). During the histamine inhalations,
      headaches increased dose-dependently in both groups. Eleven of the migraineurs
      and eight of the healthy controls experienced headaches after the inhalations.
      These headaches fulfilled the IHS criteria for migraine without aura in six of
      the migraineurs, but in none of the control subjects. Using this as a test
      parameter, the specificity of the test was 1, but the sensitivity was only 0.4.
      Our results indicate that histamine inhalation is a specific but insensitive
      laboratory test for migraine. Migraineurs should be informed about the risk of a
      migraine attack being provoked before histamine inhalation in pulmonary
      laboratories.

PMID- 8980858
TI  - Chest symptoms after sumatriptan: a two-year clinical practice review in 735
      consecutive migraine patients.
AB  - OBJECTIVES: To assess, in clinical practice, the (i) incidence, (ii) within
      patient consistency, and (iii) clinical spectrum of chest symptoms (chest
      symptoms) after subcutaneous (sc) and oral sumatriptan, and (iv) to identify risk
      factors for chest symptoms. DESIGN: Two-year retrospective survey with mailed
      self-administered questionnaire. SETTING: Neurology outpatient clinic of
      university hospital. SUBJECTS: Migraine patients with or without aura (n = 869).
      MAIN OUTCOME MEASURES: Incidence, within-patient consistency and characteristics
      of chest symptoms; demographic and clinical characteristics of patients. RESULTS:
      There were 735 (85%) respondents. Sumatriptan was used by 453 patients, during 25
      months (median), for 28000 attacks (median: 33 attacks/patient). Of sumatriptan
      users, 41% (sc) and 24% (oral) had chest symptoms in all attacks, 39% (sc) and
      58% (oral) in none, and the remaining in some attacks. Because of chest symptoms,
      10% discontinued sumatriptan. Chest symptoms mostly consisted of heavy arms and
      chest pressure, started within 5 (sc) to 30 (oral) min, and lasted 30 (sc) to 60
      (oral) min. Compared with patients without chest symptoms, patients with chest
      symptoms more often were females and younger, and went to rest immediately after
      sumatriptan administration (all p < 0.001); they also tended to have lower body
      mass indices, more severe attacks and less efficacy of sumatriptan (all 0.001 < p
      < 0.05). Patients with chest symptoms had no higher incidence of cardiovascular
      symptoms or risk factors. CONCLUSIONS: Chest symptoms are frequent, within
      patients consistent, but rarely important, adverse events of (notably sc)
      sumatriptan. The risk of chest symptoms is patient-dependent and not related,
      even opposite, to cardiovascular disease. This contradicts the hypothesis that
      chest symptoms after sumatriptan are caused by cardiac ischemia. Patient
      acceptance of chest symptoms is improved by pre-advising on the risk and nature
      of chest symptoms.

PMID- 8980860
TI  - Agraphia as the only symptom of migraine aura: a case report.
AB  - A 37-year-old female migraine patient is described, who suffered from episodes
      with pure lexical agraphia as the only symptom of migraine aura. The MRI showed
      multiple subcortical white matter lesions. Central inflammatory and demyelinating
      disorders were excluded. This case suggests that, during a migraine aura, even
      very circumscribed brain areas involved in complex neuro-psychological processing
      can be affected.

PMID- 8980859
TI  - Hyperprolactinaemia and depression induced by oxetorone.
AB  - Two cases of hyperprolactinaemia and one case of depression caused by oxetorone
      are described. These rare side effects are probably related to the
      pharmacological properties of the drug.

PMID- 8980861
TI  - Multidrug resistance in the world: the present situation.
AB  - Tuberculosis (TB) is the leading cause of death attributable to a single
      infectious pathogen with one-third of the world population infected. In the USA,
      TB rates have fallen 3 years in succession after a sustained rise since 1985.
      More important are the multidrug-resistant tuberculosis (MDR-TB) cases, which are
      thought to be largely due to the breakdown in the delivery of health care in the
      USA in conjunction with HIV infection. In countries facing the HIV epidemic, the
      overlap of these two populations leads to a rapid acceleration of active TB and
      the emergence of MDR-TB. In the USA the most recent published survey (1991)
      revealed that 3.5% of strains were resistant to isoniazid and rifampin.
      Worldwide, MDR-TB is also thought to be highly prevalent, not only because of a
      breakdown in health infrastructure but also because of inappropriate
      prescription, lack of drug availability and the use of combination capsules in
      which the drugs are not bioavailable. Key points in therapy are to order
      susceptibility tests, obtain a complete drug history, treat with an adequate
      number of effective drugs and never, ever add a single drug to a failing regimen.

PMID- 8980862
TI  - Treatment of multidrug-resistant tuberculosis in Thailand.
AB  - Tuberculosis (TB) has remained the 5th leading cause of death in Thailand for
      several years. There has been a slight change in the total number of TB cases
      notified since 1985 when the first case of HIV infection was reported. Although
      there is an increase in the incidence of TB in HIV-infected cases, the percentage
      of multidrug-resistant tuberculosis (MDR-TB) in this group is the same as in the
      HIV-negative group (2.7%). The percentages of total initial drug resistance, four
      drug resistance and MDR-TB have increased to 22.4, 1.4 and 4.8%, respectively.
      Comparable figures for acquired resistance are up to 2.5-, 10- and 6-fold,
      respectively. The rapid diagnosis and susceptibility pattern of MDR-TB are
      essential for improving therapeutic outcome. At present there is no defined
      standard regimen for MDR-TB and clinical practice has been to select a regimen of
      three to four sensitive or not previously exposed anti-TB drugs. Duration of
      treatment for 24-30 months depends on severity, previous therapy and the number
      of drug resistances. Surgery is suggested for persistent positive cases with
      localized lesions and a good cardiopulmonary reserve. The quinolone, ofloxacin,
      is a promising drug for MDR-TB, achieving a sputum conversion rate of 59-79%. A
      prospective study showed a success rate of 67% with no adverse effects. The
      current Bangkok multicenter trials on ofloxacin 600 mg daily combined with
      pyrazinamide, p-aminosalicylate, amikacin and ethambutol are ongoing. Good
      organization of ambulatory TB management combined with directly observed therapy
      will probably help to reduce the incidence of MDR-TB.

PMID- 8980863
TI  - Treatment of multidrug-resistant tuberculosis in China.
AB  - During the past decade the number and gravity of tuberculosis (TB) cases has
      continued to increase, both in developing and industrialized nations. Coupled
      with the recent emergence of multidrug-resistant tuberculosis (MDR-TB), the
      possibility that untreatable forms of the disease may become widespread has
      arisen. In China, the prevalence rate of smear-positive cases from three national
      surveys in 1979, 1984-1985 and 1990 was 187, 156 and 134/100,000, respectively,
      thus giving an annual average reduction rate of only 3.0%. This may be due to the
      accumulation of chronic cases, which is not surprising given that as many as
      84.3% of new smear-positive cases received non-organized chemotherapy. To
      counteract this situation, a strategy was developed in Beijing to practice fully
      supervised chemotherapy for all new smear-positive cases. This is now 90% with a
      cure rate also of 90%. As a result, the prevalence rate of smear-positive cases
      has dropped, with an average annual reduction of 17%. Building upon this success,
      the World Bank Loan TB Control Project in China has been carried out in 12
      provinces with 550 million people since 1992. The main objective of this project
      is to provide fully supervised, 6-month short-course chemotherapy for all newly
      detected smear-positive cases. The cure rate based on cohort analysis was 88% in
      1993. Complete data are not available on resistance although the initial and
      acquired resistance rates were 28.1 and 41.1%, respectively. MDR-TB treated with
      ofloxacin has been increasing since 1992, with 317 cases reported during the
      period 1992-1995, of which 77% showed sputum conversion.

PMID- 8980864
TI  - Treatment of multidrug-resistant tuberculosis in Taiwan.
AB  - Eighty-seven patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed
      between 1988 and 1990 were treated with isoniazid and at least three other
      effective second-line drugs based on in vitro susceptibility tests. Of these
      patients, 10% failed to adhere to the regimen and 43% remained sputum positive
      after 6 months of treatment. Only 47% showed sputum conversion within 6 months of
      treatment and 12% of them relapsed during the first year of follow-up. From
      September 1987 to July 1989, 36 patients with MDR-TB were treated with a regimen
      containing rifabutin, isoniazid and at least three other susceptible drugs. Only
      47% achieved a sustained sputum conversion. Four died during treatment due to
      disease progression. From March 1992 to July 1993, 17 cases of MDR-TB were
      treated with an ofloxacin-containing anti-TB regimen for 12-24 months. Two failed
      to adhere to the regimen for more than 1 month during the first 6 months of
      therapy. Among the remaining 15, 26% failed to achieve sputum conversion, 73%
      achieved bacterial conversion, 9 within 1 month and the other 2 within 2 months.
      No significant adverse effect was associated with ofloxacin use. We concluded
      that ofloxacin is a better choice among the more toxic and less potent second
      line drugs, and should be used along with other anti-TB drugs in treating
      patients with MDR-TB.

PMID- 8980865
TI  - Treatment of multidrug-resistant tuberculosis in Indonesia.
AB  - There is growing concern, even among developed countries, about the increasing
      incidence of multidrug-resistant tuberculosis (MDR-TB). Results are reported from
      a study investigating ofloxacin used in the treatment of 57 patients with MDR-TB.
      Patients received ofloxacin 400 mg/day as well as three other sensitive anti-TB
      drugs based on susceptibility tests. Treatment duration was 9 months. Preliminary
      results of 35 evaluable patients show 55% of MDR-TB cases converted to smear and
      culture negative within 3 months of therapy. Ofloxacin in combination with other
      sensitive anti-TB medication shows promise in the treatment of MDR-TB and further
      studies are recommended.

PMID- 8980866
TI  - Tourette disorder: a cross-cultural review.
AB  - Tourette's disorder (TD) is a complex disorder of motor and vocal tics starting
      in childhood or adolescence. Although the disorder has been researched
      extensively in North America and Europe, clinical features and associated
      conditions of TD are less well known in other cultures. The English-language
      literature relating to TD was searched for cross-cultural case reports, clinical
      investigations, and epidemiological studies, and the subsequent database was
      analyzed. The clinical characteristics of TD displayed a strong similarity across
      cultures. Demography, family history, clinical features, associated conditions,
      comorbidity, and treatment outcome were essentially the same in the various
      cultures investigated. The disorder appears world-wide, has similar clinical
      characteristics, and most likely has an underlying biological and genetic basis.

PMID- 8980867
TI  - School phobia with separation anxiety disorder: a comparative 20- to 29-year
      follow-up study of 35 school refusers.
AB  - The outcome of school phobia after age 30 years was studied with the hypothesis
      that school phobia cases would have persisting psychiatric problems, but would
      function better than nonschool refusal psychiatric patients. The subjects
      consisted of three groups. Thirty-five individuals treated for school phobia at
      ages 7 to 12 years were compared with age- and sex-matched nonschool refusal
      child psychiatric patients (n = 35) and a sample from the general population (n =
      35). School phobia cases had had more psychiatric consultation, lived with their
      parents more often than the general population group, and had fewer children than
      both comparison groups. The nonschool refusal child psychiatric patients had
      poorer psychosocial adjustment and higher rates of criminal offenses. The
      implications of the findings are discussed.

PMID- 8980868
TI  - History of childhood sexual abuse and general psychopathology.
AB  - Reported history of childhood sexual abuse (CSA) was correlated with general
      measures of psychopathology on the SCL-90-R in a sample that included inpatients
      with borderline personality disorder (BPD), inpatients with major depression, and
      a nonpatient control group. When subjects who reported abuse were compared with
      those who did not, scores for the Global Severity Index (GSI) and all subscales
      of the SCL-90-R, except for the obsessive-compulsive and somatization subscales,
      were significantly-higher. When only those subjects who reported CSA were studied
      and when specific measures of CSA were the independent variables and SCL-90-R
      subscales were the dependent variables, scores on the hostility, interpersonal
      sensitivity, and paranoia subscales of the SCL-90-R were significantly higher.
      Because a large proportion of the sample consisted of borderline patients, and
      because both the specific measures of CSA and the borderline diagnosis could
      predict similar SCL-90-R subscale results, a series of stepwise regressions were
      performed. In the first regression, diagnosis, gender, and specific measures of
      CSA were the predictor variables and SCL-90-R subscale scores were the dependent
      variables; in the second regression, SCL-90-R subscales and specific measures of
      CSA were the predictor variables and diagnosis was the dependent variable.
      Interpersonal sensitivity was the only significant predictor of the borderline
      diagnosis. We suggest that, at least in some cases, interpersonal sensitivity may
      be the constitutional/environmental substrate on which traumatic experiences
      interact to arrive at the borderline diagnosis.

PMID- 8980869
TI  - Content validity of the DSM-IV borderline and narcissistic personality disorder
      criteria sets.
AB  - This study sought to empirically evaluate the content validity of the newly
      revised DSM-IV narcissistic personality disorder (NPD) and borderline personality
      disorder (BPD) criteria sets. Using the essential features of each disorder as
      construct definitions, factor analysis was used to determine how adequately the
      criteria sets covered the constructs. In addition, this empirical investigation
      sought to: 1) help define the dimensions underlying these polythetic disorders;
      2) identify core features of each diagnosis; and 3) highlight the characteristics
      that may be most useful in diagnosing these two disorders. Ninety-one outpatients
      meeting DSM-IV criteria for a personality disorder (PD) were identified through a
      retrospective analysis of chart information. Records of these 91 patients were
      independently rated on all of the BPD and NPD symptom criteria for the DSM-IV.
      Acceptable interrater reliability (kappa estimates) was obtained for both
      presence or absence of a PD and symptom criteria for BPD and NPD. The factor
      analysis, performed separately for each disorder, identified a three-factor
      solution for both the DSM-IV BPD and NPD criteria sets. The results of this study
      provide strong support for the content validity of the NPD criteria set and
      moderate support for the content validly of the BPD criteria set. Three domains
      were found to comprise the BPD criteria set, with the essential features of
      interpersonal and identity instability forming one domain, and impulsivity and
      affective instability each identified as separate domains. Factor analysis of the
      NPD criteria set found three factors basically corresponding to the essential
      features of grandiosity, lack of empathy, and need for admiration. Therefore, the
      NPD criteria set adequately covers the essential or defining features of the
      disorder.

PMID- 8980870
TI  - Relationship between obsessive-compulsive personality disorder and obsessive
      compulsive disorder.
AB  - This study investigated the presence of obsessive-compulsive personality disorder
      (OCPD) in a group of 277 patients (88 with obsessive-compulsive disorder [OCD],
      58 with major depressive disorder [MDD], and 131 with panic disorder [Panic]) to
      test the specificity of the relationship between OCPD and OCD. OCPD is
      statistically significantly more frequent in patients with OCD than in those with
      Panic and MDD. The distribution of single criteria of OCPD in the three groups
      does not differ significantly. Discriminant analysis selects a list of items that
      provide a correct classification rate of 66% based on OCPD criteria selected by
      canonical function. OCD patients with and without OCPD do not differ in sex, age
      of onset, duration of illness, positive family history for Tics disorder/Tourette
      syndrome (TS), or morbidity risk for OCD.

PMID- 8980871
TI  - DSM-III-R personality disorders in seasonal affective disorder: change associated
      with depression.
AB  - Forty-five patients with winter Seasonal Affective Disorder (SAD) completed the
      Personality Diagnostic Questionnaire-Revised (PDQ-R) in a depressed state before
      starting therapy (light or medication), and again 14 weeks later when the scores
      on the Montgomery Asberg Depression Rating Scale (MADRS) had been reduced by an
      average of 74%. Prevalence and pattern of personality disorders (PDs) before
      treatment were similar to that found in patients with nonseasonal major
      depressive disorder (MDD) during a depressive episode. Number of categorical
      diagnoses were lower at follow-up for most PDs, but differences were not
      statistically significant. However, for dimensional scores (number of positive
      DSM-III-R criteria) significant changes were found for schizotypal, histrionic,
      narcissistic, and obsessive-compulsive PD, and for total dimensional score in
      cluster B and total score for all PDs. These changes differ from findings in
      similar studies of outpatients with nonseasonal MDD. Whether this indicates a
      specific pattern of change for patients with SAD is discussed. Multiple
      regression analysis showed a significant association between changes in positive
      PD criteria between the depressed and nondepressed state and change in depression
      score. No significant relationship was found between changes in PD criteria and
      Global Seasonality Score (GSS), a measure reflecting the sum of ratings of
      seasonal variation in sleep length, social activity, mood, weight, appetite, and
      energy level.

PMID- 8980872
TI  - Subjective experience and related symptoms in schizophrenia.
AB  - We had previously extracted two types of subjective experience of schizophrenia
      (SES); first, a feeling of inadequacy in stream of speech, thought, and action,
      associated with a distorted sense of self, and second, a feeling that excessive
      thoughts are filling and sticking to one's head, causing negative affective
      burden such as misery and oppression. This study tried to validate their content
      using conventional symptom clusters as external validators. Subjects were 63
      patients from two hospitals in Tokyo meeting ICD-10 criteria for schizophrenia.
      Positive, negative, and depressive psychopathology were measured by the Brief
      Psychiatric Rating Scale (BPRS), Scale for the Assessment of the Negative
      Symptoms (SANS), and Hamilton's Depression Scale (HDS). The two types of SES were
      measured by an original scale. The first type of SES correlated significantly
      with the negative symptoms of alogia, avolition, and attention, whereas the
      second correlated with positive and depressive symptoms. To analyze how
      schizophrenia is experienced by patients, qualitative and comprehensive
      descriptions, such as indicated by our subjective factors, will be useful.

PMID- 8980873
TI  - Consistency of symptoms in recurrent catatonia.
AB  - This study examined the consistency of symptom profiles across episodes of
      catationia. A recently developed standardized examination and symptom scale
      systematically rates 23 motor signs of catatonia, permitting symptom analysis of
      recurrent illness. Patients from the emergency room or inpatient unit were
      prospectively examined using the 23-item Bush-Francis Catatonia Rating Scale
      (BFCRS), both on initial presentation and during a later episode of catatonia.
      Five cases were identified, with a variable interval (mean, 10.7 months; range
      4.5 to 20) between episodes. All five met DSM-IV motor criteria for catatonia
      (293.89) and research criteria of more than two BFCRS signs. They showed a mean
      of 9.6 (range, 7 to 15) catatonic signs in the first episode, and 9.6 (range, 4
      to 14) signs in the second. Of the 23 individual BFCRS motor signs, a mean of
      16.6 (range, 13 to 21) showed agreement of signs (absence or presence) between
      the two episodes. The catatonic syndrome shows consistency of motor symptoms on
      recurrent episodes and the BFCRS facilitates the systematic study of catatonia.

PMID- 8980874
TI  - The Kahlbaum syndrome: a study of its clinical validity, nosological status, and
      relationship with schizophrenia and mood disorder.
AB  - Kahlbaum described catatonia as a disorder in which mood syndromes were the
      primary features and characteristic symptoms were the motor ones. However, after
      Kahlbaum this concept has not been taken into account and catatonia has been
      identified with motor features alone. In the present study, we assessed the
      clinical validity of Kahlbaum's concept of catatonia, its nosological position in
      relation to DSM-III-R, DSM-IV, and Leonhard's diagnostic criteria, and its
      relationships with schizophrenia and mood disorder. Of 567 patients consecutively
      admitted due to a functional psychotic disorder, 45 met criteria for catatonia
      according to Kahlbaum's concept (the Kahlbaum syndrome [KS]). Patients with the
      KS were differentiated from those with schizophrenia and mood disorders across a
      number of demographic and clinical variables, the differences being greater with
      the former than with the latter group. KS does not appear to fit any particular
      nosologic category, although this issue largely depends on whether schizophrenia
      and mood disorder are broadly or restrictively defined. When definitions of both
      disorders are most restrictive, as in the case of the Leonhard system, KS seems
      better accommodated as a "third psychosis". Overall, the data raise the
      possibility that KS is either a variant of mood disorder, or a distinct clinical
      entity.

PMID- 8980875
TI  - Ligand passing by the p75 tumour necrosis factor receptor enhances HIV-1
      activation.
AB  - Recently, a HIV-dependent upmodulation of the p75 tumour necrosis factor receptor
      (TNFr75) was observed using latently-infected OM-10.1 promyelocytes; although the
      participation of TNFr75 in HIV-1 activation remained undefined. Here, using
      receptor cross-linking by agonistic antibodies, no direct HIV-1 activation via
      TNFr75 was observed. Signalling via the p55 tumour necrosis factor receptor
      (TNFr55) accounted for the full extent of HIV-1 activation in OM-10.1 cultures.
      However, in tumour necrosis factor alpha (TNF-alpha) dose titration experiments,
      antibody blockade of TNFr75 decreased the dose response markedly, indicating a
      ligand passing function. TNFr75 blockade did not alter the dose response to
      agonistic TNFr55 antibody induction; verifying that the effect on the TNF-alpha
      dose response was not due to negative signalling or cytolysis. These results
      demonstrate that, although not directly involved in signal transduction resulting
      in HIV-1 activation, TNFr75 can serve a critical ligand passing function and
      permit continued HIV-1 expression during limited TNF-alpha availability.

PMID- 8980876
TI  - Induction of rapid IL-1 beta mRNA degradation in THP-1 cells mediated through the
      AU-rich region in the 3'UTR by a radicicol analogue.
AB  - A radicicol analogue (analogue A) was found to inhibit interleukin 1 beta (IL-1
      beta) and tumour necrosis factor alpha (TNF-alpha) secretion from THP-1 cells. If
      added to cells activated by interferon gamma and lipopolysaccharide, radicicol
      analogue A not only inhibited the secretion of IL-1 beta but also induced an
      extremely rapid degradation of IL-1 beta, IL-6 and TNF-alpha mRNA to undetectable
      levels within 5-8 h. This degradation is independent of translation and of the
      signal inducing transcription. The common feature of these genes is the inclusion
      of one or more copies of the mRNA-instability sequence, AUUUA, in the 3'
      untranslated region. Indeed, no destabilizing effect of radicicol analogue A
      could be observed on mRNA derived from the expression of an IL-1 beta construct
      lacking the AUUUA motifs of the 3'UTR. The effect of radicicol analogue A on
      protein/mRNA interaction and on post-translational modifications of cytoplasmic
      proteins is described. This class of compound constitutes a valuable tool for the
      further elucidation of the mechanism of mRNA degradation of cytokines and proto
      oncogenes.

PMID- 8980877
TI  - Chemokine-dependent upregulation of CD11b on specific leukocyte subpopulations in
      human whole blood: effect of anticoagulant on rantes and MIP-1 beta stimulation.
AB  - The effect of anticoagulant (heparin vs EDTA) on chemokine induced CD11b
      upregulation on neutrophils, eosinophils, and monocytes in human whole blood was
      determined. For most of the chemokines (IL-8, GRO-alpha, MCP-1, MIP-1 alpha) the
      difference in the response of leukocytes in EDTA anticoagulated blood vs those in
      heparinized blood was the degree of their maximal response, with a slightly
      higher maximal increase in CD11b expression usually seen in cells from EDTA
      anticoagulated blood. Two chemokines were exceptions to this: RANTES and MIP-1
      beta. RANTES is considered to be a stimulator of monocytes and eosinophils and
      not of neutrophils. As expected, neutrophils in heparinized whole blood did not
      respond to RANTES; however, neutrophils in EDTA anticoagulated blood had a
      significant increase in CD11b when exposed to high concentrations (1 microM) of
      RANTES. RANTES-induced CD11b expression on monocytes and eosinophils in these
      samples were the same in either heparin or EDTA. In EDTA anticoagulated blood,
      MIP-1 beta did not elicit a response in either monocytes, eosinophils or
      neutrophils; however, in heparinized blood, all three cell types increased CD11b
      expression upon exposure to 1 microM MIP-1 beta.

PMID- 8980878
TI  - Stimulation of human peripheral blood mononuclear cells by zinc and related
      cations.
AB  - Zinc is an important trace element for immune function. Here, we show that zinc
      addition in a serum- and lipopolysaccharide-free cell culture system leads to
      significantly enhanced levels of interleukin 1 beta (IL-1 beta) and tumour
      necrosis factor alpha (TNF-alpha) and to expression of the corresponding mRNA in
      human peripheral blood mononuclear cells (PBMC). Structurally related divalent
      cations like cobalt, nickel, and mercury also partially increase monokine
      secretion but to a much lower and thus insignificant extent. They fail to induce
      mRNA of TNF-alpha after 3 h of culture. Therefore, monokine induction is a zinc
      specific effect influenced by the physicochemical properties of the ion.
      Confirmation of the unique significance of zinc for immune function provides a
      better understanding of the mechanisms of specific zinc-mediated immune
      modulation.

PMID- 8980879
TI  - Effects of interleukins on Crouzon fibroblast phenotype in vitro. Release of
      cytokines and IL-6 mRNA expression.
AB  - In Crouzon's syndrome, the cranial morphogenic processes are altered due to the
      early fusion of the facial and basal cranial bones. Evidence that Crouzon
      fibroblasts have an altered phenotype which is modulated by interleukin 1 (IL-1)
      and interleukin 6 (IL-6) is provided. [3H]Thymidine incorporation and cell count
      studies showed that Crouzon fibroblasts have an accelerated proliferation rate.
      [3H]Glucosamine incorporation studies, followed by chromatography analysis of
      culture medium samples, revealed that the various classes of glycosaminoglycans
      (GAG) secreted into the medium were differently distributed in Crouzon and normal
      fibroblasts. Crouzon fibroblasts secreted less total GAG, particularly hyaluronic
      acid (HA) and heparan sulfate (HS), but a relatively greater quantity of
      chondroitin sulfate. Type I and III collagen were raised in Crouzon fibroblast
      medium whereas the concentration of fibronectin was lower than in normal cells.
      Interleukin treatment induced changes in cell growth and neosynthesis of
      extracellular matrix macromolecules. Both IL-1 and IL-6 stimulated proliferation
      of Crouzon fibroblasts, whereas only IL-6 increased [3H]thymidine incorporation
      in normal cells. IL-1 provided a drop in HA and a rise in GAG sulfates in normal
      fibroblasts, but caused an opposite effect in Crouzon fibroblasts. Type I
      collagen and fibronectin secretions are differently modulated by the cytokines in
      the two populations. Moreover, level of IL-1 able to stimulate [3H] thymidine
      incorporation into mouse thymocytes, and level of IL-1 receptor antagonist (IL
      1ra), as determined by ELISA, were higher in pathological than in normal
      fibroblasts. Also evidence that levels of IL-1 alpha and IL-6 proteins measured
      by ELISA and also IL-6 mRNA expression are enhanced in Crouzon fibroblasts is
      provided. These novel data suggested that, in Crouzon's syndrome, the
      modifications in the relative concentrations of the extracellular matrix (ECM)
      components associated with the abnormal cytokine networks may alter the balance
      of the microenvironment where the morphogenic events take place.

PMID- 8980880
TI  - Physiological effects of CNTF-induced wasting.
AB  - The authors have shown previously that in addition to its survival effects on
      neurons and glia, ciliary neurotrophic factor (CNTF) induced potent cachectic
      effects and acute phase proteins when present in the peripheral circulation at
      concentrations of < or = 10 ng/ml. These effects did not depend upon the
      induction of other cytokine family members. Described here are the specific
      physiological effects which systemic administration of CNTF can induce in somatic
      tissue. Mice implanted with C6 glioma cells, genetically modified to secrete
      CNTF, exhibited rapid catabolism of adipose tissue and skeletal muscle, depressed
      steady-state levels of glucose and triglycerides, elevations in red blood cell
      content, gall bladder hypertrophy and thymic atrophy, with a disproportionate
      loss of CD4+/CD8+ T cells. This cachectic wasting resulted in death over a period
      of 7-10 days. Implantation of the parental C6 line, or C6 cells which express a
      non-secreted form of CNTF, did not result in overt effects over this time period.
      These findings have implications both for the biology of CNTF family members, and
      the therapeutic use of factors such as CNTF in vivo.

PMID- 8980881
TI  - Transforming growth factor beta 1 is significantly elevated in plasma of patients
      suffering from renal cell carcinoma.
AB  - The levels of active and latent transforming growth factor beta 1 (aTGF-beta 1,
      ITGF-beta 1, respectively) in plasma samples were measured by enzyme-linked
      immunoabsorbent assay (ELISA). Samples were collected from patients suffering
      from renal cell carcinoma (RCC) before they underwent tumour resection. In all
      cases tested, the levels of latent TGF-beta 1 were much higher (n = 23, 41.0 +/-
      13.9, range 19.3-78.1 ng/ml) than in healthy controls (n = 21, 3.8 +/- 2.9, range
      0.6-9.9, P < < 0.0001), while active TGF-beta 1 did not differ that impressively
      (n = 38, 1.2 +/- 1.3, range 0.0-4.5 for RCC, n = 21, 0.1 +/- 0.2, range 0.0-1.1
      in controls, P < 0.001). As for TGF-beta 1 production by proximal tubulus cells
      has been shown, it was speculated that these high TGF-beta 1 levels might be due
      to secretion by the tumour, which usually originates from proximal tubuli.
      Indeed, production of TGF-beta 1 was found in culture supernatants, and it was
      possible to show TGF-beta 1 mRNA expression in tumour samples. This TGF-beta 1
      was predominantly secreted in the latent form. This is in contrast to data from
      other authors, who found TGF-beta 1 to be secreted mainly in the active form, but
      need not mean that it is inactive locally as the low pH encountered within
      tumours is in the range necessary for its activation. It is concluded that
      elevated latent TGF-beta 1 is common in RCC, is at least partially produced by
      the tumour and might be a cause for local immunosuppressive effects within the
      tumour.

PMID- 8980882
TI  - Effects of repeated administration of granulocyte colony-stimulating factor (G
      CSF) on neutrophil counts, plasma cytokine, and cytokine receptor levels.
AB  - Granulocyte colony-stimulating factor (G-CSF) induces the release of mature
      neutrophils from storage pools and stimulates differentiation of myeloid
      progenitor cells. Recently, it has been shown that a standard dose of G-CSF
      induces immunophenotypical and functional changes of neutrophils that persist for
      1 week. The authors investigated the effects of 300 micrograms of G-CSF
      administered subcutaneously twice, 1 week apart, to 10 healthy volunteers, on
      neutrophil and monocyte counts and on the plasma levels of interleukin 1 receptor
      antagonist (IL-1ra), tumour necrosis factor-alpha (TNF-alpha), soluble TNF
      receptor (sTNF-r) p55 and p75. G-CSF on both occasions increased neutrophil and
      monocyte counts and the plasma levels of all cytokines and cytokine receptors
      measured. All parameters assessed had returned to baseline prior to the second
      administration of G-CSF. The increases in neutrophil counts and plasma IL-1ra
      levels were larger following the second injection, whereas the increase in plasma
      sTNF-r p75 levels was smaller. G-CSF induced increases in monocyte counts, TNF
      alpha and sTNF-R p55 levels did not differ between the first and second
      injection. Our finding of an increased response of healthy humans to a second G
      CSF challenge 1 week following a first one may be due to long-lasting increases
      in storage pool neutrophils.

PMID- 8980883
TI  - Differential suppression of dialysis patients' lymphocyte IFN-gamma production by
      glucocorticoids and cyclosporine.
AB  - IFN-gamma is a potent pro-inflammatory cytokine involved in the immunologic
      rejection of transplanted organs. Having previously demonstrated differential
      suppressive effects of methylprednisolone (MP), prednisolone (P) and cyclosporine
      (CsA) on dialysis patients' lymphocyte proliferative responses to
      phytohaemagglutinin (PHA), we studied the effects of these drugs on dialysis
      patients' lymphocyte IFN-gamma production during mitogenic and allogeneic (MLR)
      stimulation. The mean +/- SEM 50% inhibitory concentration (ng/ml) on cell
      proliferation was significantly lower for MP than P in PHA-stimulated
      haemodialysis (HD) patients' (35 +/- 7 vs 152 +/- 25, P < 0.001) and peritoneal
      dialysis (PD) patients' (35 +/- 11 vs 134 +/- 33, P = 0.001) cultures and in HD
      patients' MLR cultures (15 +/- 3 vs 48 +/- 9, P < 0.001). The mean +/- SEM
      fractional responses (PHA or MLR + drug/PHA or MLR) in culture supernatant IFN
      gamma concentrations were significantly lower with 10(-7) M concentrations of MP
      than P in HD (0.19 +/- 0.05 vs 0.31 +/- 0.06, P = 0.01) and PD (0.30 +/- 0.11 vs
      0.46 +/- 0.11, P < 0.05) PHA cultures and in HD MLR cultures (0.15 +/- 0.04 vs
      0.28 +/- 0.07, P = 0.01). CsA (400 ng/ml) alone not only caused less than 50%
      inhibition of IFN-gamma production in 15/27 HD PHA, 6/14 PD PHA and 4/13 HD MLR
      cultures, but actually stimulated it in 9 HD and 5 PD PHA cultures. The results
      suggest that: (1) MP has greater immunosuppressive potential than P for renal
      transplant recipients; (2) the stimulation of IFN-gamma by CsA in some patients
      could be harmful in patients with initial allograft dysfunction; and (3) pre
      transplant in-vitro assessment of recipients' PBMC responsiveness to
      glucocorticoids and CsA may help individualize the post-transplant
      immunosuppressive regimen.

PMID- 8980884
TI  - Untreated Graves' but not remission Graves' immunoglobulin G preparations
      increase intracellular Ca2+ in FRTL-5 thyroid cells.
AB  - We compared immunoglobulin G (IgG) preparations obtained from untreated Graves'
      patients with those from Graves' patients in remission and normal subjects in
      terms of their activity to stimulate the phospholipase C-Ca2+ signaling. Ca2+
      mobilizing activity of the untreated Graves' IgG preparations in FRTL-5 thyroid
      cells was statistically (P < 0.01) and significantly higher than the activity of
      normal IgG preparations, whereas there was no significant difference in the
      activity between the remission Graves' and normal IgG preparations. Digital video
      imaging of fura2-loaded FRTL-5 cells confirmed that the Ca2+ mobilizing action of
      the untreated Graves' IgG preparations is an intracellular event. Phospholipase C
      activation by the untreated but not remission Graves' IgG preparations was
      statistically higher than that by normal IgG preparations. Involvement of the
      phospholipase C activation in the Ca2+ response mechanism was confirmed by the
      enhancement of the Ca2+ response by an adenosine derivative, N6(L-2
      phenylisopropyl)adenosine (PIA) which can potentiate agonist-induced
      phospholipase C activation but not the Ca2+ mobilization itself. The Ca2+
      response to the IgG preparations did not show a significant correlation with
      their cAMP response (TSAb). Therefore, the Ca2+ response to Graves' IgG
      preparations may be utilized as a functional marker for Graves' disease in
      addition to TSAb.

PMID- 8980885
TI  - Effects of simvastatin on the number and composition of apoproteinB-containing
      lipoproteins in hypercholesterolemia: analysis of apoproteinB in each lipoprotein
      fraction by highly sensitive latex method.
AB  - We investigated the effects of simvastatin on the number and composition of
      apoproteinB (apoB)-containing lipoproteins in thirteen patients with
      hypercholesterolemia type IIa or IIb by measuring apoB by a highly sensitive
      latex method. Patients received simvastatin 5-10 mg (7.7 +/- 0.7 mg, mean +/-
      SEM) daily for 83-218 days (131 +/- 13 days). In both types of patients,
      treatment with simvastatin significantly reduced plasma cholesterol levels (mean
      +/- SEM mg/dl: in type IIa from 234.4 +/- 5.4 to 171.4 +/- 7.8, in type IIb from
      242.4 +/- 11.6 to 178.8 +/- 9.6), low density lipoprotein (LDL) cholesterol
      levels (from 122.6 +/- 5.2 to 68.5 +/- 4.6, and from 115.6 +/- 14.0 to 70.4 +/-
      11.6 in the two types, respectively) and LDL apoB levels (from 94.5 +/- 6.6 to
      60.6 +/- 7.0, and from 85.0 +/- 8.4 to 56.6 +/- 6.2, respectively). There was no
      significant change in cholesterol, triglyceride (TG) or apoB in very low density
      lipoprotein (VLDL). High density lipoprotein (HDL) cholesterol did not change in
      this study. With respect to lipoprotein composition, the ratio of either
      cholesterol or TG to apoB in VLDL, intermediate density lipoprotein (IDL) and LDL
      did not change significantly, but that of TG to apoB in the IDL fraction
      increased in type IIa. Simvastatin promotes more effective reduction in
      cholesterol and apoB in LDL than in VLDL, probably by increasing the hepatic LDL
      receptor which preferentially binds LDL.

PMID- 8980886
TI  - Splenic macrophages can modify steroidogenesis of Leydig cells.
AB  - A large amount of LH/hCG treatment given to male rats is known to suppress the
      enzyme activity of cytochrome P450c17 in Leydig cells for 48 h. A high dose
      LH/hCG injection is also known to allow immunocytes, such as macrophages, to
      migrate into the testicular interstitial compartment. It has not been known,
      however, whether these cells play a role in that suppression. In this study, we
      examined if splenic macrophages have any effects on testosterone secretion from
      Leydig cells by culturing rat testicular interstitial cells (TIC). Splenic
      macrophages co-cultured with TIC significantly suppressed testosterone secretion.
      Macrophages co-cultured reduced both progesterone to testosterone conversion and
      the amount of cytochrome P450c17 mRNA. The conditioned medium (SMCM), prepared by
      culturing macrophages for 12 h, significantly reduced either testosterone
      secretion from TIC or progesterone to testosterone conversion by TIC. These
      results indicate that splenic macrophages suppress testosterone secretion from
      Leydig cells by suppressing the cytochrome P450c17 enzyme in vitro, and that this
      effect is mediated at least in part by some soluble factors secreted from
      macrophages. Splenic macrophages migrating into the testis after LH/hCG
      stimulation could play a role in suppressing cytochrome P450c17 in Leydig cells.

PMID- 8980887
TI  - Plasma free thyroxine (FT4) concentrations during hemodialysis in patients with
      chronic renal failure: effects of plasma non-esterified fatty acids on FT4
      measurement.
AB  - Plasma free T4 (FT4) concentrations could be increased during hemodialysis in
      patients with chronic renal failure (CRF) because an increase in non-esterified
      fatty acids (NEFA) could interfere with the binding of T4 to thyroxine-binding
      globulin. To evaluate the effect of hemodialysis on the FT4 concentration in
      patients with CRF, we measured the FT4 in 39 patients with CRF by four assay
      methods including equilibrium dialysis, the 125I-T4 analog method and enzyme
      immunoassay. The addition of the fatty acid sodium oleate to normal pooled sera
      led to a marked increase in FT4 as measured by equilibrium dialysis (Model FT4).
      A moderate increase in the serum FT4 concentration also was observed with an IMX
      enzyme immunoassay kit, whereas the Coat-A-Count analog method demonstrated no
      interference by sodium oleate. The mean serum FT4 prior to hemodialysis measured
      by equilibrium dialysis did not differ significantly from that in the normal
      control, although those measured by analog methods (Coat-A-Count and Amerlex) and
      IMX were subnormal. The FT4 by IMX were albumin-dependent, and the values
      decreased as the samples were serially diluted, but Model FT4 was not affected by
      the albumin level or the serial dilution. FT4 by Model FT4 showed a marked
      increase beginning 10 min after the start of dialysis, and it correlated well
      with the plasma concentration of NEFA and the NEFA/albumin molar ratio. The other
      three assay methods, including one which is not affected by NEFA, did not show a
      change in FT4 at 10 min, but a significant increase of 11 to 17% was observed by
      the end of dialysis. The TSH concentration decreased significantly during
      hemodialysis. These data suggest that (1) the low serum FT4 in hemodialysis
      patients measured by some immunoassay methods may be an underestimation due to
      the low albumin level; (2) FT4 actually increases during hemodialysis due to the
      actual increase in NEFA, although the marked increase in FT4 during hemodialysis
      as measured by equilibrium dialysis is an overestimation due to the in vitro
      generation of NEFA; and (3) one should beware of aberrations in thyroid hormone
      parameters during hemodialysis and potential complications.

PMID- 8980888
TI  - A case of Schmidt syndrome accompanied by a pituitary adenoma.
AB  - Schmidt syndrome consists of adrenal insufficiency and Hashimoto's thyroiditis,
      which are probably caused by an autoimmune process. We encountered a patient who
      manifested severe generalized fatigue due to Schmidt syndrome recurrently. The
      endocrinological examination tests on the patient showed that the increase in
      thyroid stimulating hormone (TSH) and ACTH concentrations were not remarkable,
      despite hypo-function of the peripheral glands. Subsequent cranial magnetic
      resonance imaging (MRI) exhibited the existence of a pituitary tumor. The
      pathological findings on the resected tumor and endocrinological stimulation
      tests proved that the tumor was a FSH-producing adenoma. Although involvement of
      the pituitary region in Schmidt syndrome on rare occasions presents as
      hypophysitis, no pituitary adenoma has previously been reported in association
      with this syndrome. We present a patient with Schmidt syndrome and an
      accompanying FSH-producing pituitary adenoma. The coexistence of these disorders
      suggests that the functioning pituitary tumor might be considered as a pituitary
      lesion in Schmidt syndrome.

PMID- 8980889
TI  - Parasellar chronic inflammatory disease presenting Tolosa-Hunt syndrome,
      hypopituitarism and diabetes insipidus: a case report.
AB  - We describe a 60-year-old man with a history of Tolosa-Hunt syndrome associated
      with intermittent painful ophthalmoplegia and a visual disturbance on the left
      side, who presented with signs and symptoms of severe hypoadrenalism and diabetes
      insipidus. Magnetic resonance imaging demonstrated enlargement of the hypophysis
      and infundibulum and left cavernous sinus. An endocrinologic study revealed
      anterior pituitary dysfunction and diabetes insipidus. The patient underwent a
      transsphenoidal biopsy which revealed chronic inflammation in the hypophysis,
      mucosa of the sphenoid sinus, and dura mater. The patient was treated with
      steroids that decreased the size of the hypophysis and infundibulum, but the
      symptoms of anterior pituitary insufficiency and diabetes insipidus have
      persisted. The chronic inflammation of the hypophysis and infundibulum is thought
      to have spread from the cavernous sinus.

PMID- 8980890
TI  - Acutely exacerbated hypertension and increased inflammatory signs due to
      radiation treatment for metastatic pheochromocytoma.
AB  - Hypertension and norepinephrine hypersecretion in a 59-year-old woman suffering
      from malignant pheochromocytoma with multiple metastases were appropriately
      controlled with alpha- and beta- blockers, and alpha-methyltyrosine (alpha-MT), a
      catecholamine-synthesis inhibitor. Metastasized vertebrae were treated with
      external radiation to relieve pain, but this treatment had to be interrupted at a
      total dose of 20 Gy because the patient suffered acutely exacerbated hypertension
      (200/110 mmHg), tachycardia (160 beats/min) and a low-grade fever. Simultaneously
      her serum levels of LDH, potassium, urea nitrogen, creatinine, white blood cell
      count, CRP and norepinephrine were significantly increased, suggesting that this
      episode was due to radiation-induced tissue destruction and the leakage of
      catecholamines and possibly interleukin-6, a cytokine mediating inflammation
      which is reportedly present in pheochromocytoma. The marked hypertension was
      controlled by continuous i.v. administration of phentolamine and propranolol.
      Although radiation therapy effectively relieves pain due to neoplasmic metastasis
      to the bone, physicians should be aware that life-threatening complications such
      as the above occur in malignant pheochromocytoma. Sufficient pretreatment with
      adrenergic blocking agents and/or alpha-MT and careful monitoring of the
      patient's general condition during radiation therapy, even at a low dose, are
      highly recommended.

PMID- 8980891
TI  - Soluble intercellular adhesion molecule-1 concentrations in patients with
      subacute thyroiditis and in patients with Graves' disease with or without
      ophthalmopathy.
AB  - Increased circulating soluble ICAM-1 (sICAM-1) levels has been previously
      reported in Graves' disease (GD) patients with or without ophthalmopathy (GO) and
      in patients with toxic nodular goiter but not in patients with subacute
      thyroiditis. Conflicting results have also been reported about the usefulness of
      sICAM-1 levels as a marker for the activity of hyperthyroidism. We have therefore
      determined sICAM-1 levels by a sandwich enzyme linked immunosorbent assay (ELISA)
      method in 10 patients with subacute thyroiditis (Group 1), who are at the initial
      or acute phase of thyroiditis, in 10 hypothyroidic patients with Hashimoto's
      thyroiditis (Group 2), in 10 patients with euthyroid nodular goiter (Group 3), in
      10 patients with untreated GD patients with active ophthalmopathy (Group 4), in
      10 hyperthyroid GD patients without clinical ophthalmopathy (Group 5), in 10
      patients with GO who are euthyroid and treated with glucocorticoids for 3 months
      (Group 6) and in 20 normal subjects (Control Group). Groups 1,2,4,5 and 6 (P <
      0.00001 for Groups 1,4,5,6 and P < 0.05 for Group 2) but not Group 3 showed
      increased sICAM-1 levels compared with the control group. However Groups 4 and 6
      (patient with GO) showed significantly higher sICAM-1 levels (P = 0.0003 for
      Group 4 and P = 0.00013 for Group 6) than Group 5. Furthermore Group 4 showed
      slightly but not significantly higher sICAM-1 levels than Group 6. Mean sICAM
      levels were significantly decreased 3 months after glucocorticoid treatment
      (Group 6), but had not returned to normal levels. Three patients did not respond
      to steroid therapy and their sICAM-1 levels were not decreased. We concluded that
      patients with GO with or without hyperthyroidism and patients with subacute
      thyroiditis have elevated sICAM-1 levels. Moreover, sICAM-1 levels reflect the
      degree of inflammatory activity in the thyroid gland or orbital tissue
      independent of the thyroidal status, since we found elevated levels in both
      hyperthyroidism and hypothyroidism.

PMID- 8980892
TI  - Osteogenic action of parathyroid hormone-related peptide (1-141) in rat ROS
      cells.
AB  - To examine the autocrine/paracrine effect of parathyroid hormone-related peptide
      (PTHrP) on osteoblast function, the entire coding region of rat PTHrP (1-141)
      cDNA inserted into the expression vector was stably transfected into the rat
      clonal strain of the osteoblast-like cell, ROS 17/2.8, and established stable
      transfectants. Using the PTHrP-overexpressing ROS cells (ROS/PLP/6), we analyzed
      in vitro cell characterization and in vivo osteogenic properties. As expected,
      overexpression of endogenous PTHrP in vitro induced PTH/PTHrP receptor down
      regulation confirmed by Northern blots, receptor binding assays, and functional
      analysis. The established transfectants indicated a decreased growth rate
      compared with the original non-transfected ROS 17/2.8. Although cAMP production
      induced by exogenous PTH was suppressed in ROS/PLP/6, the stimulatory effects of
      forskolin and chorela toxin showed no significant difference between the original
      ROS 17/2.8 and transfected cells, but the in vivo osteogenic properties were
      histologically potentiated in transfectants with increased bone matrix and
      acceleration of mineralization within tumors. The levels of osteocalcin and
      osteopontin mRNAs were also increased in transfectants. The down-regulated in
      vitro PTH/PTHrP receptor mRNA was restored in in vivo tumor tissues. Our study
      provides clear evidence that the in vivo osteogenic function in ROS cells is
      potentiated by PTHrP, through an autocrine/paracrine mode of action.

PMID- 8980893
TI  - Acute expression of the PRL receptor gene after ovariectomy in midpregnant mouse
      mammary gland.
AB  - In order to examine the time-dependent expression of the PRL receptor (PRL-R)
      gene at lactogenesis, the level of PRL-R mRNA was determined following
      ovariectomy in pregnant mouse mammary gland. Following reverse transcription, the
      quantity of mRNA was measured by the competitive polymerase chain reaction. The
      casein (a 22,000 molecular weight component) mRNA level was measured as a marker
      for milk synthesis. Following ovariectomy, the onset of abortion occurred mostly
      at 22-23 h and the level of casein mRNA began to increase at 12 h. The long and
      short forms of PRL-R mRNAs were detected in a molar ratio of 1:0.2 on day 12 of
      pregnancy. Eight h after ovariectomy, the long form of PRL-R mRNA began to
      increase, showing a bell-shaped profile with the highest peak at 16 h. The short
      form of PRL-R mRNA was at low levels and remained constant. The levels of the
      long form of PRL-R mRNA decreased similarly in the presence and absence of foster
      pups from 24 to 48 h. Conversely, casein mRNA were maintained at high levels by
      supplying foster pups. The level of the long form of PRL-R mRNA reached a maximum
      prior to abortion. The present experiments demonstrated that the acute expression
      of the PRL-R gene occurred in the mammary gland at lactogenesis.

PMID- 8980894
TI  - Effect of interferon-beta on thyroid function in patients of chronic hepatitis C
      without preexisting autoimmune thyroid disease.
AB  - The effect of interferon-beta (IFN-beta) on thyroid function was studied in
      patients with chronic hepatitis who had no preexisting thyroid disease. Eleven
      patients (9 males and 2 females) aged 20 to 65 years, with a mean age of 47.7 +/-
      13.5 years, were treated with 6 million units of IFN-beta intravenously every day
      for 8 weeks. During IFN-beta administration (4th to 8th week of treatment), both
      serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations
      decreased significantly (P < 0.0005 and P < 0.05, respectively): FT4, 1.37 +/-
      0.17 to 1.09 +/- 0.12 ng/dl, and FT3, 3.71 +/- 0.45 to 3.28 +/- 0.34 pg/ml. On
      the other hand, serum TSH increased significantly from a baseline of 1.70 +/-
      0.82 to 3.34 +/- 1.98 microU/ml during IFN-beta administration (P < 0.005). Four
      to eight weeks after cessation of treatment, the mean serum FT4 concentration was
      similar to that during IFN-beta administration (1.04 +/- 0.14 ng/dl), but mean
      serum FT3 and TSH concentrations returned to pre-treatment levels (FT3, 3.57 +/-
      0.42 pg/ml and TSH, 1.60 +/- 0.84 microU/ml). Both reverse T3 and thyroglobulin
      were essentially unchanged. Tests for anti-thyroglobulin and anti-microsomal
      antibodies were negative in all the patients. These results indicate that IFN
      beta may inhibit thyroid function in patients without preexisting thyroid disease
      irrespective of humoral immune responses.

PMID- 8980895
TI  - Effects of atipamezole, an alpha 2-adrenergic antagonist, and somatostatin on
      xylazine-induced growth hormone release in calves.
AB  - In order to clarify the mechanism of xylazine-induced GH release, we investigated
      the effects of atipamezole, a selective alpha 2-adrenergic antagonist, and
      somatostatin (SRIF) on xylazine-stimulated GH release in calves. Xylazine
      injection (0.30 mg/kg BW, iv) induced a rapid increase in the GH concentration.
      When atipamezole was used in combination with xylazine, it blunted the increase
      in the plasma GH concentration induced by the xylazine injection. The GH levels
      at 15-50 min after the simultaneous injection of xylazine and atipamezole were
      significantly (P < 0.05) lower than the corresponding values in the animals given
      xylazine alone. The area under the GH response curve for 120 min after the
      simultaneous injection of xylazine and atipamezole was significantly (P < 0.05)
      smaller than that for the xylazine alone. A series of five intravenous injections
      of 1 mg of SRIF at 10-min intervals also blunted xylazine-stimulated GH release.
      Atipamezole partially suppressed xylazine-induced hyperglycemia, but SRIF
      completely suppressed the hyperglycemia for the first 60 min after the xylazine
      injection and the suppression by SRIF was stronger than that by atipamezole. On
      the other hand, both atipamezole and SRIF failed to blunt xylazine-induced
      hypoinsulinemia. The present results suggest that xylazine stimulates GH release
      via the alpha 2-adrenergic pathway in cattle, but the mechanism of xylazine
      induced hyperglycemia remains to be determined.

PMID- 8980896
TI  - Incomplete testicular feminization syndrome: studies on androgen receptor(AR)
      function, AR gene analysis, and aromatase activities at puberty and long-term
      observations of clinical and hormonal features from infancy to puberty.
AB  - A female infant with partial androgen insensitivity (PAIS) was first seen at 4
      months of age with slight virilization of the genitalia and externally palpable
      testes. Sex chromosome was 46,XY. She received left orchidectomy and exploratory
      laparotomy at 2 yr of age. At exploratory laparotomy, neither a uterus nor
      fallopian tubes were found. The right testis was preserved by fixing it at the
      external inguinal ring expecting spontaneous pubertal maturation. After
      discharge, serum levels of LH, FSH, testosterone (T) and estradiol (E2) were
      measured annually, and the steroid responses to hCG stimulation were examined
      every two yr. At the age of 10 yr, she developed breasts and a very feminine body
      habitus. At 12 yr, she received a clitoroplasty and right orchidectomy. The
      fibroblast cultures were made from the genital skin whereby androgen receptor
      (AR) binding was assessed by radioreceptor assay using 3H-DHT as the ligand, and
      thermoinstability of AR was noted despite normal maximum binding (Bmax) and
      dissociation constant (Kd) at 22 degrees C. But another binding experiment with
      3H-Mibolerone resulted in the lack of receptor binding. AR gene analysis with
      direct sequencing of coding exons of the gene revealed no abnormality of the AR
      gene. 5 alpha-reductase activity was normal. Aromatase activity appeared to be
      enhanced in the genital skin fibroblast (GSF) cells as well as in the testicular
      tissue. The results of these studies indicated that the patient had PAIS with
      impaired AR functions and increased aromatase activity. After the discharge, the
      patient has maintained feminine phenotype, receiving estrogen therapy with
      mestranol 0.02 mg/day po.

PMID- 8980897
TI  - Acute promyelocytic leukemia in the course of acromegaly: a case report.
AB  - Acromegaly is an uncommon disease due to excessive amounts of growth hormone.
      Benign and malignant tumors have been reported in acromegalic patients. A 41-year
      old female patient who had been followed up because of acromegaly by the
      endocrinology department for two years, was admitted to the hematology department
      for the evaluation of pancytopenia and the related signs and symptoms. Dopamine
      agonists were being used till a diagnosis of 'acute promyelocytic leukemia' was
      made. Occurrence of 'acute promyelocytic leukemia' in the course of acromegaly
      may have been caused by excessive endogenous GH or may be a coincidental
      situation.

PMID- 8980898
TI  - Familial isolated hypoparathyroidism: case report with serum PTHrP examination.
AB  - We report a family, with isolated hypoparathyroidism. The proband was a 24-year
      old woman, who presented with paresthesia of both hands. She had a mild degree of
      extrapyramidal signs, such as rigidity and decrease in arm swinging. Laboratory
      examinations revealed low PTH levels, mild hypocalcemia and hyperphosphatemia in
      the proband, her father, a younger brother and a younger sister, whereas her
      mother had normal serum calcium, phosphorus and PTH levels. These results
      indicate that four members of the family were affected, suggesting autosomal
      dominant inheritance. Brain CT revealed calcification of basal ganglia in the
      proband, her father and a younger sister, but not in her younger brother. Serum
      PTH-related protein (PTHrP) levels were examined, and found to be slightly high
      only in the father of the proband.

PMID- 8980899
TI  - Changes in the size of adrenal glands in acute pulmonary tuberculosis with
      therapy.
AB  - Adrenal glands may be involved during both acute and chronic tuberculosis. They
      are enlarged in acute pulmonary tuberculosis. We aimed to investigate the changes
      in adrenal size in acute pulmonary tuberculosis before and after therapy in a
      prospective study. Eleven hospitalized patients with newly diagnosed sputum
      positive pulmonary tuberculosis were studied. Basal cortisol levels were measured
      in the patients before and after the therapy. Cortisol levels were also measured
      30 and 60 min after Synacthen (250 micrograms i.v.) injection in the patients
      before the therapy. The size of the adrenal glands was measured by computerized
      tomography. The maximum width perpendicular to the long axis of the body of the
      gland, maximum width of the medial and lateral limbs and the length of the
      adrenals were measured. All measurements were done before and after the eight
      month anti-tuberculosis therapy. All 11 patients had an intact adrenal cortisol
      reserve. Both the width and length of the right and left adrenal glands were
      significantly greater before the therapy than after the therapy. We conclude that
      adrenal enlargement demonstrated by computerized tomography in acute pulmonary
      tuberculosis is reduced after appropriate therapy.

PMID- 8980900
TI  - Manifestation of subclinical diabetes insipidus due to pituitary tumor during
      pregnancy.
AB  - We describe a case of diabetes insipidus (DI) due to a pituitary tumor in a 33
      year-old pregnant woman who developed a sudden onset of polyuria (over 8 l/day)
      and polydipsia at 30 weeks of gestation. Her plasma concentration of vasopressin
      (AVP) was low compared with high serum osmolality (298 mOsm/kg), and her urine
      output was well controlled by treatment with desmopressin acetate (DDAVP).
      Cranial magnetic resonance imaging (MRI) demonstrated a 1.8 x 1.2-cm pituitary
      tumor, but she did not have any disturbance in the release of anterior pituitary
      hormones. The serum concentration of cystine aminopeptidase (CAP) was within the
      normal range for a woman at 34 weeks of gestation. After an uncomplicated
      delivery of a healthy girl, her polyuria gradually resolved. The size of the
      pituitary tumor gradually decreased in parallel to a reduction in her urine
      output, but a silent hemorrhage was detected in her pituitary gland 4 weeks after
      the delivery. Although pregnancy is sometimes associated with central DI, the
      occurrence of DI due to pituitary tumor under pregnancy is rare. The basal AVP
      recovered to within the normal range, but the low response of AVP secretion to
      high osmolality persisted. In this case, pregnancy may affect the manifestation
      of subclinical DI. This case may therefore enhance our understanding of the
      mechanisms of DI during pregnancy.

PMID- 8980902
TI  - Isolation and cellular localization of the decorin endocytosis receptor.
AB  - The small dermatan sulfate proteoglycans decorin and biglycan are efficiently
      internalized by a variety of cells of mesenchymal origin. This process is
      modulated, at least under tissue culture conditions, by cell surface-associated
      heparan sulfate proteoglycans. Receptor proteins of 51 and 26 kDa, respectively,
      bind to leucine-rich repeat structures of the core proteins of the small
      proteoglycans but also to highly sulfated domains of heparan sulfate. The 51 kDa
      protein was purified from rat brain tissue by subcellular fractionation, heparin
      affinity chromatography and subsequent SDS-PAGE, and was used for raising a
      polyclonal antiserum. Affinity-purified antibodies also recognize the 26 kDa
      protein and a few other low molecular weight proteins, suggesting that these
      proteins represent proteolytic degradation products of the 51 kDa receptor. By
      confocal laser microscopy, it could be demonstrated that the affinity-purified
      antibody reacted at 0 degree C with a protein that became internalized and was
      transported to a perinuclear compartment during 15 min of incubation at 37
      degrees C. These findings provide direct evidence that the receptor protein(s)
      are internalized together with the ligand and reach an endosomal compartment
      where further sorting can occur.

PMID- 8980901
TI  - Site-directed mutagenesis of recombinant equine chorionic
      gonadotropin/luteinizing hormone: differential role of oligosaccharides in
      luteinizing hormone- and follicle-stimulating hormone-like activities.
AB  - Equine chorionic gonadotropin (eCG) consists of highly glycosylated alpha- and
      beta-subunits and belongs to the glycoprotein hormone family that includes LH and
      FSH. eCG is a unique member of the gonadotropin family because it elicits
      response characteristics of both FSH and LH in other species than the horse. To
      determine the biological role of the N-linked oligosaccharide at Asn 56 of the
      alpha-subunit and O-linked oligosaccharides at the carboxyl-terminal peptide
      (CTP) of the beta-subunit, two mutant eCGs, in which Asn 56 of the alpha-subunit
      was replaced with Gln (eCG alpha 56/beta) or CTP was deleted (eCG alpha/ beta
      CTP), were produced by site-directed mutagenesis and transfecting chinese hamster
      ovary (CHO-K1) cells. LH- and FSH-like activities were assayed in terms of
      testosterone production and aromatase activity in primary cultured rat Leydig
      cells and granulosa cells, respectively. The wild type eCG showed similar LH- and
      FSH-like activities to native eCG in the in vitro bioassays. The LH-like activity
      of eCG alpha 56/beta was greatly reduced, whereas that of eCG alpha/beta-CTP was
      unaffected, demonstrating that the oligosaccharide at Asn 56 of the alpha-subunit
      of eCG plays an indispensable role in LH-like activity. Interestingly, the FSH
      like activity of eCG alpha 56/beta was increased markedly in comparison with the
      wild type, and that of eCG alpha/beta-CTP was also considerably increased. These
      data indicate that the dual activities of eCG, LH- and FSH-like activities, could
      be separated by removal of the N-linked oligosaccharide on the alpha-subunit Asn
      56 or CTP-associated O-linked oligosaccharides.

PMID- 8980903
TI  - Monensin-induced redistribution of enzymes and products from Golgi stacks to
      swollen vesicles in plant cells.
AB  - We have tested the hypothesis that monensin treatment of plant cells leads to the
      transfer of Golgi enzymes to the monensin-induced swollen vesicles using sycamore
      maple suspension-cultured cells and immunolabeling techniques. Cells treated for
      20 and 60 min with 10 microM monensin were labeled with anti-V-H(+)-ATPase, anti
      xyloglucan (XG) sidechain (CCRC-M1), anti-pectic polysaccharide (JIM7 and CCRC
      M2), and anti-N-glycan (anti-beta Xyl, and anti-alpha Fuc) antibodies. Our
      results demonstrate that monensin causes most H(+)-ATPase to be displaced from
      the Golgi cisternae (label distribution in control cells: 11% cis, 32% medial,
      57% trans cisternae) to the swollen vesicles, which explains why these vesicles
      remain swollen after detachment from the Golgi/trans Golgi network cisternae. We
      also show that the content of complete XG molecules (defined by completed
      trisaccharide sidechains) in the swollen vesicles increases 1.5-fold between the
      20 and 60 min samples, suggestive of the transfer of functional XG backbone and
      sidechain synthesizing enzymes from the trans Golgi compartment to the swollen
      vesicles. In contrast, no increase in either anti-pectin antibody or N-glycan
      antibody labeling of the swollen vesicles was observed between the 20 min and 60
      min monensin samples. Both of these latter types of molecules depend for their
      synthesis on enzymes located in multiple membrane compartments upstream from the
      trans Golgi cisternae, which greatly decreases the probability of transfer of
      complete enzyme systems to the swollen vesicles. Thus these latter findings do
      not contradict the anti-H(+)-ATPase and the anti-XG labeling data, which strongly
      support the Golgi enzyme displacement theory.

PMID- 8980904
TI  - Time course of vinblastine-induced autophagocytosis and changes in the
      endoplasmic reticulum in murine pancreatic acinar cells: a morphometric and
      biochemical study.
AB  - The time course of the vinblastine(-sulfate; 10 mg/kg body weight, single
      injection)-induced enlargement and subsequent regression of the autolysosomal
      compartment was studied by electron microscopic morphometrical and cell
      biochemical methods in order to gain information concerning some key problems of
      this major route of intralysosomal degradation of the cell's endogenous
      macromolecules and structures. Detailed analysis of the dynamics of the total
      autophagic vacuole (AV) compartment and its different subcompartments (early,
      advanced, late, and fused AVs), as well as of changes of rough-surfaced
      endoplasmic reticulum (RER) showed: 1. Pancreatic acinar cells react to
      vinblastine biphasically, i.e. two expansion phases of the AV compartment, the
      first in the 0 to 90 min and the second in the 2 to 8 h post-injectional periods,
      were detected. 2. Fusions of AVs are not inhibited by vinblastine, at least
      during the second expansion phase when cytoplasmic volume fraction (CVF) of fused
      AVs steadily increased until the 12th h. Fusion of early, advanced and late AVs
      or composition of fused complex vacuoles (AVc) are somehow regulated, as the
      proportion of the three AV stages from the CVF of AVc, was maintained constant
      throughout the second expansion phase. 3. Stimulation of autophagosome formation
      and resulting substrate overload seems to be the primary mode of action by which
      vinblastine causes the enormous expansion of the autolysosomal compartment. 4.
      Degranulation of the rough-surfaced endoplasmic reticulum (RER) membranes occurs
      in a biphasic fashion, similarly to the volume and surface changes of the AV
      compartment, thus supporting our previous hypothesis, that labilization or change
      of RER may have a role in the formation of autophagosomes. 5. Vinblastine-induced
      autophagocytosis is a selective process, as mitochondria, Golgi elements and
      zymogen granules are very much underrepresented, whereas RER is more than twice
      overrepresented in the volume of early AVs, when compared to their volume
      fraction in the whole cytoplasm. 6. Immunogold electron microscopy revealed the
      presence of ubiquitinylated proteins in advanced and late, but not in early AVs.

PMID- 8980905
TI  - Light microscopic analysis of ligand-induced actin filament suprastructures.
AB  - In this study, we describe a simple light microscopic assay which allows to
      rapidly determine the ligand-induced organization of actin filaments into
      specific suprastructures, such as web-like arrangements or bundles. The validity
      of this assay is demonstrated by accompanying low shear (falling ball)
      viscometry. While the visually identified webs demonstrated viscosity values
      significantly higher than the F-actin control, the bundles were characterized by
      viscosities distinctly lower than that of the control. In addition, we show that
      at least in some cases, the type of actin suprastructure formed depends on the
      molar ratio between the ligand and actin filaments. The assay should be useful to
      assess the conditions under which a particular ligand leads to a specific actin
      filament organization, to determine quickly the biological activity of
      recombinant proteins or isolated actin-binding domains, and to define new F-actin
      ligands.

PMID- 8980906
TI  - Depolymerization of macrophage microfilaments prevents induction and inhibits
      activity of nitric oxide synthase.
AB  - We have investigated the relationship between peritoneal murine macrophage
      cytoskeleton and nitric oxide (NO) synthase (NOS). Activation of the cells with
      lipopolysaccharide plus interferon-gamma (LI) induced iNOS, detected by nitrite
      or by labeled L-citrulline production and by a specific antibody against
      macrophage iNOS. Addition of cytochalasin B (a microfilament-depolymerizing
      agent) caused a dose-dependent inhibition in NO production by macrophages,
      whereas colchicine (a microtubule depolymerizing agent) inhibited it only by 20%
      and not dose-dependently. Addition of cytochalasin B together with LI abolished
      nitrite and L-citrulline accumulation as well as the amount of iNOS antigen in
      activated macrophage. Moreover, addition of cytochalasin B 6 or 12 h after
      stimulus, also decreased the nitrite and L-citrulline production by macrophages
      although iNOS antigen content by Western blot was the same in the presence or in
      the absence of cytochalasin B added 12 h after activation. Since cytochalasin B
      failed to inhibit iNOS activity directly, its inhibitory effects on NO production
      by macrophages is likely to be indirect, through microfilament network in central
      regions of cells, but not in filaments seen at pseudopodia or edging processes.
      Our findings demonstrate that disruption of microfilaments but not of
      microtubules prevents the iNOS induction process and inhibits its enzymatic
      activity in activated macrophages.

PMID- 8980907
TI  - Immunocytochemical characterization of the follicle-associated epithelium of
      Peyer's patches: anti-cytokeratin 8 antibody (clone 4.1.18) as a molecular marker
      for rat M cells.
AB  - For the characterization and identification of potential molecular markers of M
      cells, the follicle-associated epithelium (FAE) of Peyer's patches from the small
      intestine of rats was analyzed by indirect immunofluorescence and immunogold
      electron microscopy. The expression of intermediate filament proteins in the FAE
      was found to be heterogeneous. Immunoreactivity of a specific monoclonal
      cytokeratin 8 antibody (clone 4.1.18) was selectively found in cells which were
      additionally characterized by the lack of staining for alkaline phosphatase in
      their apical membranes. In the FAE, this property is an accepted criterium for
      the presence of M cells. Further, these cells were found to be devoid of mucin
      and were thus distinct from goblet cells. The antigen recognized by the clone
      4.1.18 is expressed in substantially higher amounts in M cells of Peyer's patches
      as compared to neighboring epithelial cells or "normal" enterocytes and thus can
      be employed as an intracellular molecular marker for M cells of Peyer's patches
      in rats.

PMID- 8980908
TI  - Localization of Dictyostelium myoB and myoD to filopodia and cell-cell contact
      sites using isoform-specific antibodies.
AB  - To date, five myosin I heavy chain genes (myoA-E) have been sequenced in
      Dictyostelium. Among them, myoB, myoC and myoD possess tail domains that contain
      a putative membrane-binding domain, a nucleotide-insensitive actin-binding site,
      and an src homology (SH)-3 domain. In this study, we have determined the
      intracellular localizations of myoB and myoD by immunofluorescence using isoform
      specific antibodies raised against bacterially expressed fusion proteins. MyoB is
      concentrated at the leading edges of lamellipodia and at sites of cell-cell
      contact in both stationary and aggregation stage cells. Based on its distinctive
      appearance, we have named the myosin I-rich, interdigitating cell-cell contact
      structure in the stationary stage cells "zipper". To analyze the staining of
      filopodia, we employed the ratio imaging technique. We find that myoB is present
      in filopodia in either a uniform or an apical staining pattern. Like myoB, myoD
      is concentrated in leading edges of lamellipodia and at sites of cell-cell
      contact in stationary stage cells. MyoD is also present in filopodia, although
      the intensity is weaker than that of myoB staining. Despite persistence of myoD
      protein in the cells, myoD largely disappears from lamellipodia and cell-cell
      contact regions in aggregation stage cells, suggesting the occurrence of a
      developmentally regulated relocalization to the cytoplasm. While these results,
      along with the striking similarity in their tail domain structures, suggest that
      myoB and myoD have overlapping functions, differences in their localization in
      developing cells indicate that they have unique functions as well.

PMID- 8980910
TI  - Hydrocortisone is involved in regulating the proliferation and differentiation of
      mouse epidermal melanoblasts in serum-free culture in the presence of
      keratinocytes.
AB  - Mouse epidermal melanoblasts preferentially proliferated from disaggregated
      epidermal cell suspensions derived from newborn mouse skin in serum-free medium
      (MPM) supplemented with dibutyryl adenosine 3', 5' cyclic monophosphate (DBcAMP)
      and basic fibroblast growth factor (bFGF). After 12 days, almost all
      keratinocytes died, and pure and enriched cultures of melanoblasts (approximately
      90%) and melanocytes (approximately 10%) could be obtained. In order to clarify
      the role of hydrocortisone (HC) which is thought to be important for the
      regulation of melanocyte proliferation and differentiation, the hormone was added
      to MPM from the initiation of primary culture. The proliferation of melanoblasts
      was inhibited by HC in a dose-dependent manner. Instead, most of the
      proliferating melanoblasts were induced to differentiate into melanocytes by HC
      in a dose-dependent manner. A small number of pure melanoblasts derived from
      primary cultures at 12 days with MPM depleted of DBcAMP and bFGF were cultured
      with MPM with or without HC in the presence of secondary keratinocytes that were
      subcultured from a pure population of primary keratinocytes in a serum-free
      medium. The inhibition of the proliferation of melanoblasts by HC as well as the
      stimulation of the differentiation of melanoblasts into melanocytes by HC was
      observed in the presence of keratinocytes, but not in the absence of
      keratinocytes. Conditioned media or extracts prepared from pure keratinocytes in
      serum-free primary culture failed to replace the role of keratinocytes. These
      results suggest that HC plays an important role in the regulation of the
      proliferation and differentiation of mouse epidermal melanoblasts in culture in
      cooperation with factors supplied by keratinocytes.

PMID- 8980909
TI  - Urinary trypsin inhibitor efficiently inhibits urokinase production in tumor
      necrosis factor-stimulated cells.
AB  - We demonstrated that urinary trypsin inhibitor (UTI) efficiently inhibits soluble
      and tumor cell-associated plasmin activity and subsequently inhibits tumor cell
      invasion and metastasis. The effect of UTI on tumor necrosis factor-alpha (TNF)
      induced stimulation of urokinase-type plasminogen activator (uPA) in cultured
      human umbilical vein endothelial cells (HUVEC) and in the promyeloid leukemia
      U937 cells was studied. uPA antigen was evaluated in the cell lysate and in the
      conditioned media by enzyme-linked immunosorbent assay, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and Western blot. TNF can promote the
      production of uPA in HUVEC and in U937 cells. The PKC inhibitors (H7, calphostin
      C, and staurosporine) inhibited TNF-induced uPA expression and secretion in a
      dose-dependent manner. Analysis of the expression of cell surface receptor-bound
      uPA by flow cytometry using uPA-specific MAb indicates that induction of uPA
      expression by TNF was inhibited when these cells were incubated with UTI. On the
      other hand, treatment of the cells with UTI alone failed to alter uPA production.
      UTI also reduced the secretion of uPA in TNF-treated cells. UTI was as effective
      as PKC inhibitors in inhibiting uPA expression by TNF. Incubation of the cells
      with UTI, however, had no effect on the ability of PMA to stimulate cell
      associated uPA expression. These data suggest that UTI may influence the PKC
      dependent protein kinase pathway in uPA expression. The study on intracellular
      pathways involved in UTI modulation of uPA will enhance our understanding of the
      role that UTI plays in uPA-mediated cellular invasion.

PMID- 8980911
TI  - Isolation and cultivation of endothelial cells derived from human placenta.
AB  - Endothelial cells were isolated from human full-term placenta by perfusion with
      trypsin solution via the umbilical cord vein. Human placental endothelial cells
      (HPEC) were successfully grown and kept in culture. HPEC exhibited endothelial
      characteristics as judged by morphology of confluent monolayers, staining with
      low density lipoprotein, binding of Ulex europaeus I lectin, and immunostaining
      against von Willebrand factor, alpha-thrombomodulin, VE-cadherin and a series of
      integrins. Different growth requirements and particular morphological
      characteristics indicated the different vascular origin of HUVEC and HPEC.

PMID- 8980912
TI  - Immunocytochemical localization of multicatalytic protease complex (proteasome)
      during generation of murine IL-2-activated natural killer (A-NK) cells.
AB  - Murine IL-2-activated, adherent natural killer (A-NK) cells produce proteolytic
      activities (including a chymase and a tryptase) which appear to be components of
      the proteasome/multicatalytic proteinase complex and appear to represent the
      mouse homologues of the rat A-NK cell A-NKP 2 and A-NKP 1 protease components.
      The chymase is readily inhibited by Z-Gly-Gly-Phe chloromethylketone (Z-GGF) and
      to a lesser extent by N-tosyl-L-phenylalanyl-chloromethylketone (TPCK). In
      addition, this activity is inhibited by 3,4-dichloroisocoumarin (DCI), a suicide
      inhibitor for both chymotryptic and tryptic proteolytic enzymes. Protease
      inhibitors reduced A-NK cell-mediated cytotoxicity against P815 target cells,
      most prominently with inhibitors of chymotryptic and tryptic enzymes, including
      TPCK, DCI and Z-GGF. A polyclonal rabbit antibody raised against rat liver
      proteasome immunofluorescently labeled the cytoplasm of 4-day-cultured murine A
      NK cells, multiple granules in 5 to 6-day cultures and large intracytoplasmic
      pools in cells cultured longer. Ultrastructurally this shift in labeling over
      time corresponded to an immunogold redistribution to non-membrane delineated
      mucoid masses. A minor nuclear labeling was noted at all time points, whereas the
      cisternae of the endoplasmic reticulum or Golgi region were negative. It is
      concluded that murine A-NK cells synthesize and accumulate proteasome in large
      intracytoplasmic pools, non-delineated by membranes which can occupy up to 80% of
      the A-NK cellular volume. The potential function of the proteasome produced by A
      NK cells including cell-mediated cytotoxicity against tumor target cells remains
      to be elucidated.

PMID- 8980913
TI  - Calcium homeostasis in intraerythrocytic malaria parasites.
AB  - The fluorescent indicator, fura-2, AM, was used to measure free calcium
      concentrations in the intraerythrocytic malaria parasites of Plasmodium chabaudi
      and Plasmodium falciparum. In both species the free cytosolic calcium
      concentration was maintained at low levels (between 40 and 100 nM throughout the
      maturation process. Digital image analysis of the indicator fluorescence was
      performed on parasites and evaluated with the aid of a calibration of the calcium
      response, based on permeabilized parasites, exposed to calcium buffers. This
      again revealed that free calcium concentrations in the intact parasite are
      maintained at a predetermined level, regardless of the free calcium in the
      surrounding milieu. Both species of parasites are thus capable of regulating
      their internal free calcium levels with high precision, presumably by means of
      calcium pump ATPases. A small but significant elevation of the cytosolic free
      calcium concentration by the tumor promoter, thapsigargin, may be taken to
      reflect the presence of calcium stores in the endoplasmic reticulum in P.
      falciparum.

PMID- 8980914
TI  - Recovery of interphase nuclei from extreme structural alterations in centrifuged
      fern protonemal cells.
AB  - Nuclear ability to recover morphologically and physiologically from tremendous
      elongation induced by centrifugation was investigated in single-celled
      protonemata of the fern Adiantum capillus-veneris. Basipetal centrifugation at a
      strength of ca. 2000 g for more than 1 h caused an extremely long (more than 500
      microns), thread-like chromatin-containing extension of the nuclear envelope in
      the centrifugal direction. The nucleolus was either located inside a terminal
      widening of the extension, or it was detached from the thread and located outside
      the nucleus. Such enucleolation occurred in about half of the nuclei during 3 h
      of basipetal centrifugation. After centrifugation, the nuclei recovered
      morphologically by completely reducing the chromatin thread. One day after the
      end of centrifugation, all nuclei again contained a nucleolus, indicating that
      nucleolar regeneration had taken place in the interphase nucleus. Almost all
      basipetally centrifuged cells were still able to divide under white light
      conditions. A strong delay in the division time course may be attributed to
      recovery processes of the nuclear internal order. The remarkable ability of the
      Adiantum interphase nuclei to recover morphologically and physiologically is
      assumed to be due to processes which also drive the maintenance of the functional
      nuclear structure during interphase.

PMID- 8980915
TI  - Localization by ultrastructural in situ hybridization of mitochondrial
      transcripts in epithelial cells of a Drosophila subobscura deletion mutant.

PMID- 8980917
TI  - How harmless is FFA enhancement?
AB  - Standard heparin as well as low molecular weight heparin (LMWH) increase lipid
      levels in serum. It has been reported that a diet rich in long chain saturated
      fatty acids can enhance the susceptibility to experimental thrombosis. The
      mechanism by which serum fatty acids may provoke thrombosis is not clear. It is
      possible that the fatty acids change the properties of the cell membrane and
      thereby modify the response of platelets to aggregating agents. Heparin and its
      LMW fractions, by mobilising lipoprotein lipase that hydrolyses serum
      triglycerides (TG), cause the serum TG to increase, a well known "clearing
      effect' of heparin in turbid lipemic plasma. This effect may have no significance
      when it lasts for a short time; however, a long-lasting heparin effect on TG
      serum levels may have important consequences. The purpose of this study was to
      examine the time span of the action of heparin and its fractions and to
      investigate variations in the concentration of digoxin, which is a compound with
      narrow therapeutic width. The investigated substances after 2 days
      administration, provoked serum concentration increases of free fatty acids (FFA),
      TG and HDL-C. Seven days after stopping drug administration, FFA and HDL-C levels
      remained high, while triglycerides declined. Serum total cholesterol remained
      unchanged throughout. Digoxin levels increased non-significantly after heparin
      administration and during swimming stress, while a lipid diet caused a serum
      digoxin concentration increase.

PMID- 8980916
TI  - The influence of food on the absorption and metabolism of drugs: an update.
AB  - Food-drug interactions can lead to a loss of therapeutic efficacy or toxic
      effects of drug therapy. Generally, the effect of food on drugs results in a
      reduction in the drug's bioavailability; however, food can also alter drug
      clearance. The benefits of considering metabolism and pharmacokinetic information
      in the drug discovery process have been highlighted by Humphrey and Smith (79)
      and the process of rational drug design should include considerations of the
      chemistry, pharmacology and pharmacokinetics of the drug (80) and the impact of
      diet on these parameters.

PMID- 8980918
TI  - Pharmacokinetics and bioavailability of drotaverine in humans.
AB  - The pharmacokinetics and bioavailability of drotaverine was studied in 10 healthy
      volunteers after administration of single 80 mg oral and intravenous doses of the
      HCl salt of the drug, in a crossover fashion. Plasma and urine samples were
      analyzed for the unchanged drug by HPLC. The pharmacokinetic parameters, such as
      elimination half-life, plasma clearance, renal clearance and apparent volume of
      distribution, were not influenced by the route of drug administration. The drug
      was mainly eliminated by non-renal routes since renal clearance accounted for
      only 0.31 +/- 0.13% of the total plasma clearance. The absolute bioavailability
      was variable and ranged from 24.5-91% with a mean of 58.2 +/- 18.2% (mean +/-
      SD). It is suggested that the high variation in the bioavailability of
      drotaverine HCl after oral administration may result in significant
      interindividual differences in therapeutic response.

PMID- 8980919
TI  - Effect of Tamarindus indica L. on the bioavailability of aspirin in healthy human
      volunteers.
AB  - The influence of Tamarindus indica L. fruit extract incorporated in a traditional
      meal on the bioavailability of aspirin tablets 600 mg dose was studied in 6
      healthy volunteers. There was a statistically significant increase in the plasma
      levels of aspirin and salicylic acid, respectively, when the meal containing
      Tamarindus indica fruit extract was administered with the aspirin tablets than
      when taken under fasting state or with the meal without the fruit extract. The
      Cmax, AUC0-6h and t1/2 for aspirin increased from 10.04 +/- 0.1 mg/ml to 28.62 +/
      0.21 mg/ml (P < 0.05); 14.03 +/- 0.11 mg/ml.h to 86.51 +/- 0.21 mg/ml.h (P <
      0.085) and 1.04 +/- 0.12 h to 1.50 +/- 0.44 h (P < 0.05) respectively. There was
      no change in the tmax (0.50 +/- 0.17 h) but there was a decrease in the kel from
      0.633 +/- 0.22 to 0.463 +/- 0.29 (P < 0.05). Similarly, the Cmax, AUC0-6h and kel
      for salicylic acid rose from 43.84 +/- 0.21 mg/ml to 68.19 +/- 0.71 mg/ml (P <
      0.05); 171.59 +/- 0.07 mg/ml.h to 266.22 +/- 0.21 mg/ml/.h (P < 0.05) and 7.37 +/
      0.29 to 19.30 +/- 0.21 (P < 0.05), respectively. The tmax decreased from 2.0 +/-
      0.18 h to 1.0 +/- 0.08 h (P < 0.05) and t1/2 from 0.25 +/- 0.21 h to 0.184 +/-
      0.11 h (P < 0.05). The study has indicated that Tamarindus indica L. fruit
      extract significantly increased the bioavailability of aspirin.

PMID- 8980920
TI  - Weibull function fits to pharmacokinetic data of ribavirin in man.
AB  - Weibull function C = Bts-1exp(-lambda ts) was used to describe plasma
      concentration-time data of ribavirin in 6 healthy subjects following an i.v. dose
      of 600 mg. A good fit was found in each of the subjects, where the coefficients
      of determination r2 were > 0.99. The parameters estimated were as follows: B,
      5.90 +/- 1.86 micrograms.h1-s; lambda, 0.607 +/- 0.156 h-s; and s, 0.339 +/-
      0.085, respectively. The results were compared with those by triexponential
      function. By providing lower values of AIC and SD, as well as higher values of
      r2, the Weibull function proved to be superior to triexponential function for
      data of 3 subjects. These results indicated that both Weibull function and
      triexponential function provided a good fit of plasma concentration-time data of
      ribavirin in man following an i.v. dose.

PMID- 8980922
TI  - The effect of food on the relative bioavailability of deflazacort.
AB  - The effect of high- and low-fat meals on the relative bioavailability of
      deflazacort tablets was investigated in 12 healthy, adult males who were
      administered 36 mg deflazacort under fasted and fed conditions in a crossover
      fashion. Serial plasma samples were drawn up to 24 h post-dose and quantified for
      the active metabolite 21-desacetyl deflazacort (DFZ 21-OH) by a rapid and
      sensitive HPLC method. Following deflazacort administration with high-fat and low
      fat meals and under fasted conditions, DFZ 21-OH area under the curve to infinity
      averaged 508.39 +/- 131.70, 510.05 +/- 148.30 and 511.90 +/- 188.16 ng.h/ml. DFZ
      21-OH Cmax averaged 156.31 +/- 33.31, 156.85 +/- 40.17 and 188.05 +/- 53.35 ng/ml
      for high-fat, low-fat and fasted treatments, respectively. Differences in Cmax
      between the fed versus fasted treatments were statistically significant (P <
      0.05). The decrease in Cmax under fed conditions was accompanied by an increase
      in mean Tmax of approximately 17-85% compared to fasted conditions. As expected,
      terminal half-life was not affected. These data indicate that co-administration
      of deflazacort tablets with high-fat and low-fat meals leads to a small decrease
      in rate but does not affect its extent of absorption.

PMID- 8980921
TI  - Paracetamol metabolism in two ethnically different Spanish populations.
AB  - The 24 h urinary excretion of paracetamol and its metabolites following a single
      oral dose of 1.5 g was compared in two ethnically different Spanish populations:
      39 volunteers from the Basque country and 32 from Alicante. The urinary
      concentrations of unchanged paracetamol and its glucuronide, sulphate, cysteine,
      and mercapturic acid conjugates were determined by high-performance liquid
      chromatography. Statistically significant differences in the urinary excretion of
      unchanged paracetamol and the fractional urinary recovery of each conjugate
      between subjects from Alicante and subjects from the Basque country were not
      found. In both populations, an inverse relationship between glucuronide and
      sulphate conjugation following a bimodal frequency distribution pattern was
      found. In contrast to paracetamol oxidation, intersubject variation in
      paracetamol conjugation was negligible. The urinary excretion of unchanged
      paracetamol was higher in smokers than in nonsmokers. As compared with other
      studies, the urinary excretion of oxidation-derived paracetamol metabolites in
      both Spanish populations was intermediate and significantly different than that
      found in Caucasians from Scotland and West Africans (Ghana). This may determine a
      susceptibility to paracetamol hepatotoxicity following overdosage in the Spanish
      population.

PMID- 8980924
TI  - Clinical response and plasma concentrations of amitriptyline and its metabolite
      nortriptyline in depressive patients.
AB  - Although many attempts have been made, to date no convincing evidence exists of a
      relationship between plasma concentrations of amitriptyline (AT), its active
      metabolite nortriptyline (NT) and clinical response. Fifteen patients with
      primary depression (according to DSM-IV) were divided in two groups according to
      given doses: (I) 6 patients received 3 x 50 mg of AT daily; and (II) 9 patients
      received 3 x 25 mg of AT daily, for 6 weeks. The clinical status was determined
      with Hamilton Depression Rating Scale. Both investigated doses were
      therapeutically effective. AT and NT plasma concentrations were assayed by high
      performance liquid chromatography. Following administration of 3 x 50 mg of AT
      daily, the correlation of concentrations of AT, NT, total AT + NT and clinical
      response were rAT = -0.702 (P < 0.1), rNT = -0.761 (P < 0.1), rAT + NT = -0.741
      (P < 0.1). The linear and very high correlation were also present with
      concentrations of AT, NT, total AT + NT and clinical response in depressive
      patients on 3 x 25 mg AT daily: rAT = -0.785 (P < 0.02), rNT = -0.811 (P < 0.01),
      rAT + NT = -0.848 (P < 0.01). Our results support a high correlation between
      AT/NT plasma concentrations and clinical response indicating that therapeutic
      monitoring of AT and its metabolite, NT, can provide eventual clinical response.

PMID- 8980923
TI  - Effect of neuroleptics on ethanol-treated rats.
AB  - The subject of the present study is the effect of neuroleptic anaesthetics on
      sleeping time and some biochemical parameters of ethanol-treated and untreated
      rats. In one set of experiments involving four groups of animals, we studied how
      ethanol (12%, v/v) consumption for 10, 20 and 30 days influenced the sleeping
      time of animals after administration of a single dose of the investigated
      anaesthetics. In the other set of experiments, we studied the combined effect of
      30 day ethanol consumption and each of the anaesthetics administered to the
      animals in multiple doses for 3 h, by determining the contents of cytochrome P450
      and glutathione and the activities of glutathione peroxidase and lipid
      peroxidation. The results show that statistically significant changes of measured
      parameters are due to the action of ethanol and not of the neuroleptic
      anaesthetics.

PMID- 8980925
TI  - Seasonal variations in the kinetics of bupivacaine in the mouse.
AB  - Very few studies have been devoted to the influence of the time of the year, i.e.
      seasonal variations, on drug kinetics. This study aims to evaluate whether or not
      the kinetics of bupivacaine varied according to the time of the year in mice.
      Eight groups of 30 animals each received bupivacaine (20 mg/kg i.p.) at a
      specific month of the year, i.e. February (second week), March (first week), May
      (fourth week), July (first week), September (fourth week), November (second and
      third weeks) and December (first week), at the same time of the day (10.00 h).
      Total bupivacaine serum concentrations were determined by using a specific gas
      liquid chromatographic method on blood samples collected by decapitation at 0.25,
      0.5, 1, 2, 4 and 6 h after drug administration. Pharmacokinetic variables were
      determined, according to a non linear fitting method (two compartment open
      model). All data were compared by ANOVA and the influence of the month of the
      year was estimated by Cosinor analysis. According to the month of the year, the
      kinetic parameters were significantly different except for Vd: the maximal Cmax
      occurred in July, the highest Tmax occurred in May, the maximal T1/2 beta and the
      maximal AUC were observed in February. The mechanisms underlying these variations
      may depend on seasonal variations of resorption, distribution, metabolism and
      elimination.

PMID- 8980926
TI  - Pharmacokinetics and metabolism of N-(2-hydroxyethyl)-2,5-[14C]-pyrrolidine (HEP,
      Epolamine) in male healthy volunteers.
AB  - N-(2-hydroxyethyl)-pyrrolidine (HEP, Epolamine) is a strong base used to salify
      organic acids of pharmaceutical interest in order to improve their solubility in
      water. Diclofenac-HEP (Flector) is the first example of an epolamine salt of a
      drug. In this study, [14C]-HEP was administered by oral route (300 mg, about 50
      microCi/subject) to 3 volunteers with the aim to investigate its plasma profile
      and to calculate the relevant pharmacokinetic parameters. The experimental data
      correlated with a two-compartment pharmacokinetic model. Total radioactivity in
      urine and faeces was also measured. The radioactivity was excreted preferentially
      by the faecal route (about 65% of the dose administered in the 0-72 h collection
      interval). Urinary excretion accounted for about 30% of the dose and occurred
      very rapidly (about 22% of the dose was in the 0-8 h collection interval).
      Metabolic investigations were carried out on urine samples. TLC analysis with
      radioscan detector indicated a main radioactive zone, accounting for about 98% of
      the radioactivity in the plate. After scraping off and purification of the
      radioactive areas, the compound isolated (Met I) was analysed by gas
      chromatography-mass spectrometry with electron-impact ionization process. The
      structure of the metabolite was postulated to be pyrrolidine N-oxide.

PMID- 8980927
TI  - In heme catabolism C2 and C4 vinyl groups reduction of cobalt protoporphyrin
      forms cobalt mesoporphyrin and alters the nature of action of the
      metalloporphyrin in vivo.
AB  - Heme is a tetrapyrrolic ring with iron as the central metal atom and acts as a
      prosthetic group for a number of enzymes, e.g. cytochromes and globins. It also
      plays an important role in the regulation of transcription, translation, protein
      translocation and erythroid differentiation. Thus, heme regulation is under
      strict control in the body. Our studies on the regulatory enzymes of heme
      anabolism, aminolevulinic acid synthetase (ALA-S), and of catabolism, heme
      oxygenase (HMOX), in the spleen has revealed that cobalt protoporphyrin acts as
      an inducer of HMOX. It is revealed that by alteration of side groups at C2 and C4
      changes the nature of action of Co-protoporphyrin from an inducer to a strong
      inhibitor of HMOX activity. All the three analogues Co-protoporphyrin, Co
      mesoporphyrin and Co-hematoporphyrin have been shown to induce the ALA-S activity
      to the similar extent. NADPH-cytochrome c reductase, a microsomal membrane bound
      enzyme, is required by HMOX for the enzymatic conversion of heme into biliverdin
      IXc and is also required for NADPH-dependent lipid peroxidation in the
      microsomes. It has been observed that Co-mesoporphyrin causes an inhibition of
      HMOX activity and consequently leads to an induced level of microsomal NADPH
      dependent lipid peroxidation.

PMID- 8980928
TI  - Interspecies scaling: predicting clearance of anticancer drugs in humans. A
      comparative study of three different approaches using body weight or body surface
      area.
AB  - From this study it is proposed that the clearance of anti-cancer drugs may be
      best estimated if they follow the following trend: (i) that if the exponent of
      the allometric equation (clearance vs body weight) lies between 0.55-0.75 (0.75
      was chosen after Kleiber's power rule (18)), then a simple allometric equation
      can predict the clearance reasonably well; (ii) if the exponent of the allometric
      equation lies between 0.75 to approximately 0.90, clearance can be reasonably
      predicted using CL x MLP; and (iii) if the exponent of the allometric equation is
      > or = 0.90, the clearance can be predicted using the product of clearance and
      brain weight.

PMID- 8980929
TI  - Scoring of liver biopsies: are we doing it right?

PMID- 8980930
TI  - Transjugular intrahepatic portosystemic stent-shunt (TIPSS) insertion as a
      prelude to orthotopic liver transplantation in patients with severe portal
      hypertension.
AB  - OBJECTIVE: To investigate the impact of preoperative transjugular intrahepatic
      portosystemic stent-shunt (TIPSS) on patients undergoing liver transplantation.
      DESIGN: A retrospective non-randomized comparative clinical study. SETTING:
      Tertiary referral institution. PATIENTS, PARTICIPANTS: Twenty-four patients with
      liver cirrhosis, portal hypertension and gastro-oesophageal varices who underwent
      liver transplantation. INTERVENTIONS: TIPSS insertion had been performed
      preoperatively in 12 patients. MAIN OUTCOME MEASURES: Operative dissection times
      and blood transfusion requirements during liver transplantation. Postoperative
      complication rate. Cumulative patient and graft survival. RESULTS: There were no
      significant differences in outcome measures between patients with and without
      previous TIPSS insertion with respect to recipient hepatectomy times (mean 192
      min (126-280) versus 196 min (145-254)), total operating time (mean 484 min (330
      690) versus 486 min (370-580)), intraoperative blood transfusion (mean 11 units
      (2-29) versus 12 units (2-30)), intraoperative fresh frozen plasma transfusion
      (mean 9 units (1-16) versus 11 (2-23) units), patient survival (83% versus 92%
      cumulative 1-year survival), graft survival (80% versus 83% cumulative 1-year
      survival), or postoperative complication rates. CONCLUSION: TIPSS insertion is
      feasible and relatively safe as a 'bridge to transplantation' in patients who
      have had a variceal haemorrhage. There is little evidence that preoperative TIPSS
      insertion directly affects the performance of liver transplantation as TIPSS
      neither, hinders nor facilitates surgery or post operative survival. Although it
      is important that the potential hazards of TIPSS extension into the inferior vena
      cava or superior mesenteric vein be recognized, liver transplant surgeons need
      not be unduly concerned about the overall impact of TIPSS as it becomes more
      universally available in the management of variceal haemorrhage.

PMID- 8980931
TI  - Superoxide dismutase activity in duodenal ulcer patients.
AB  - OBJECTIVE: To investigate whether duodenal ulcer (DU) is associated with
      increased free radical generation at the site of ulceration and to attempt,
      indirectly, to confirm the hypothesis by determining activity of free radical
      scavengers such as superoxide dismutase (SOD). STUDY DESIGN: Prospective study
      comparing SOD activity in biopsies taken from the ulcer edge, and antrum in DU
      patients before and after one month of treatment to SOD activity in biopsies from
      the duodenal bulb and antrum in a control population. SETTING: Institute of
      Gastroenterology of a university hospital. STUDY POPULATION: Twenty-five patients
      with DU. The diagnosis was confirmed by endoscopy. MEASUREMENTS: SOD activity in
      biopsy specimen, red blood cells (RBC) and serum was measured using the
      cytochrome c method by spectrophotometry and expressed as U SOD/mg protein.
      Helicobacter pylori was diagnosed by the rapid urease test (CLO test) from antral
      biopsies. RESULTS: SOD activity was markedly depleted in the ulcer edge (2.78 +/-
      0.9 U SOD/mg protein) as compared to the same patients after one month of
      treatment (4.59 +/- 2.2 U SOD/mg protein) (P = 0.05) and to biopsies from the
      duodenal bulb in control population (6.7 +/- 2.4 U.SOD/mg protein) (P = 0.05).
      SOD activity in the antrum of both groups was similar. There was no difference in
      SOD activity in RBC and serum of both groups. CONCLUSION: Products of free
      radical reactions are implicated in the pathogenesis of DU disease. SOD, which is
      a key enzyme in gastric mucosal protection, is depleted significantly in the
      ulcer edge compared with controls and increases after healing. However, it is not
      clear whether this abnormality in oxygen free radical metabolism reflects, rather
      than causes, the condition which characterizes DU.

PMID- 8980933
TI  - Helicobacter pylori reinfection is rare in peptic ulcer patients cured by
      antimicrobial therapy.
AB  - BACKGROUND: Cure of H. pylori infection in peptic ulcer patients significantly
      reduces the risk of ulcer recurrence. Since data on the rate of H. pylori
      reinfection in patients undergoing successful anti-H. pylori therapy are sparse,
      this study was conducted with the aim of determining the H. pylori reinfection
      rate in peptic ulcer patients receiving antibacterial treatment to heal their
      ulcer and cure H. pylori infection. METHODS: A total of 217 patients with H.
      pylori-associated duodenal or gastric ulcer were followed up after treatment with
      various antibacterial regimens resulting in histologically documented cure of H.
      pylori infection. Endoscopic and histological examinations were performed 4 weeks
      after completion of treatment and after 1, 2 and 5 years, or whenever dyspeptic
      symptoms occurred. To assess the H. pylori status two antral and two corpus
      biopsies were obtained for histological examination. RESULTS: Out of 217 patients
      with initially cured H. pylori infection 175 were available for endoscopic follow
      up. At the time of analysis, 44 patients were re-examined after 1 year, 113
      patients after 2 years and 18 patients after 5 years, giving a total of 360
      patient years of follow-up. The mean duration of follow-up was 24.7 months. H.
      pylori reinfection was confirmed histologically in eight patients, three of whom
      becoming H. pylori-positive again within the first year of follow-up. Six of the
      eight patients with H. pylori reinfection also suffered an ulcer relapse. Eight
      cases of reinfection in 360 patient years represents an overall reinfection rate
      of 2.2%. Within the first 2 years of follow-up the reinfection rate was 0.8% per
      year. CONCLUSION: Our data suggest that H. pylori reinfection is rare in peptic
      ulcer patients receiving successful anti-H. pylori therapy. H. pylori reinfection
      frequently coincides with ulcer recurrence. Cure of H. pylori infection results
      in cure of peptic ulcer disease, provided H. pylori reinfection does not occur.

PMID- 8980932
TI  - Reinfection and duodenal ulcer relapse in south-east Asian patients following
      successful Helicobacter pylori eradication: results of a 2-year follow-up.
AB  - OBJECTIVES: To determine the reinfection rate of Helicobacter pylori and duodenal
      ulcer relapse rate in a group of patients followed up long term. DESIGN:
      Prospective study. PATIENTS AND METHODS: Patients were followed up endoscopically
      at 3, 6, 12 and 24 months after successful H. pylori eradication and duodenal
      ulcer healing. H. pylori status was determined by culture, rapid urease test,
      Gram's stain of a fresh tissue smear and histological examination of antral
      biopsies and rapid urease test and histological examination of corpus biopsies.
      MAIN OUTCOME MEASURES: Duodenal ulcer healing, H. pylori reinfection. RESULTS:
      Thirty-eight patients with duodenal ulcer disease (35 active, 3 healed) had
      successfully eradicated H. pylori following treatment with omeprazole/amoxycillin
      (n = 11), omeprazole/amoxycillin/metronidazole (n = 16) and colloidal bismuth
      subcitrate/ amoxycillin/metronidazole (n = 11). All patients with active duodenal
      ulcer had healed ulcers at the end of therapy. Thirty-five of 38 patients were
      seen according to schedule up to 2 years; two patients were seen up to 12 months
      and one up to 6 months only. Reinfection with H. pylori was not recorded in any
      of our patients. Shallow duodenal ulcers were noted in three patients at 1-year
      follow-up, two of whom admitted to taking non-steroidal anti-inflammatory drugs
      (NSAIDs); H. pylori status was negative in all three. Subsequent follow-up
      revealed spontaneous healing of the ulcers in all three patients. At 2 years, one
      patient whose H. pylori status was negative had recurrence of duodenal ulcer. All
      of the three patients who defaulted subsequent to follow-up were negative for H.
      pylori and had healed ulcers on follow-up endoscopy at 6 and 12 months.
      CONCLUSION: Reinfection rate with H. pylori was zero in a group of South-East
      Asian patients who had successfully eradicated the infection. Duodenal ulcer
      relapse was also low (2.9%) in this group of patients at 2 years.

PMID- 8980934
TI  - Helicobacter pylori infection in a healthy population in Spain.
AB  - OBJECTIVE: To determine the seroprevalence of Helicobacter pylori infection in
      healthy individuals in Spain and its relationship with different epidemiological
      features. PATIENTS AND METHODS: The study was conducted on a large group of
      healthy individuals without ulcer disease antecedents or other gastrointestinal
      disease; moreover, information, was obtained on symptoms attributable to the
      gastrointestinal tract, smoking, alcohol consumption, non-steroidal anti
      inflammatory drug (NSAID) use as well as the presence of peptic ulcer disease
      antecedents among first-degree relatives. The H. pylori infection status was
      ascertained by immunoglobulin G (IgG) antibody determination, using a
      quantitative enzyme-linked immunosorbent assay. RESULTS: Three hundred and eighty
      one individuals (138 males and 243 females) were included in the study (mean age:
      34.3 +/- 12.9 years; range: 5-77). Two hundred and two individuals (53%) were
      positive for H. pylori IgG antibodies. A consistent increase in H. pylori
      infection seroprevalence with increasing age was observed. No association was
      observed between H. pylori infection and consumption of alcohol, NSAID use or
      smoking. On the other hand, the presence of digestive symptoms and peptic ulcer
      disease antecedents among first-degree relatives were associated with a higher
      prevalence of infection in a given individual (P < 0.05). CONCLUSION: H. pylori
      infection seroprevalence in healthy individuals in Spain is similar to that in
      countries with high socio-economic standards and other Western countries.
      Digestive symptoms and previous antecedents of peptic ulcer disease in first
      degree relatives were associated with a higher prevalence of Helicobacter pylori
      infection.

PMID- 8980935
TI  - Ranitidine in a twice daily triple-therapy regimen for the eradication of
      Helicobacter pylori.
AB  - OBJECTIVE: To compare the efficacy and safety of ranitidine 300 mg twice daily
      plus amoxycillin 1000 mg twice daily for 2 weeks (RA2) with ranitidine 300 mg
      twice daily, amoxycillin 1000 mg twice daily, plus tinidazole 500 mg twice daily
      for 2 weeks (RAT2) for the eradication of Helicobacter pylori. DESIGN:
      Prospective, randomized, double-blind, parallel-group study in patients who were
      H. pylori positive on 13C urea breath test (13C UBT). SETTING: Twenty-four UK
      consultant gastroenterologists entered mostly hospital out-patients. PATIENTS: A
      total of 232 patients with gastric or duodenal ulceration or endoscopic
      appearances suggestive of gastritis (160 male, 72 female, mean age 51) were
      entered following routine endoscopy; 223 were H. pylori positive on 13C UBT.
      Patients with medical conditions or medications which could interfere with study
      response or measurements and those at risk of pregnancy were excluded. Two
      hundred and three patients completed the study. INTERVENTIONS: Patients underwent
      endoscopy with biopsy for rapid urease (CLO) test. Those who were positive had a
      13C UBT. Patients were randomized to receive RA2 or RAT2. Eradication of H.
      pylori was assessed by 13C UBT 4 weeks after completion of therapy. Blood was
      taken for haematological and biochemical screening at the beginning and end of
      treatment. MAIN OUTCOME MEASURE: H. pylori eradication at least 28 days after end
      of treatment. RESULTS: In the intention-to-treat sample analysis, H. pylori was
      eradicated in 78/115 patients (68%) taking RAT2 and 42/108 patients (39%) taking
      RA2. In the per-protocol sample analysis H. pylori eradication was successful in
      68/79 patients (86%) taking RAT2 and 36/71 patients (51%) taking RA2. One hundred
      and seventeen patients experienced 242 adverse events. CONCLUSION: Twice daily
      ranitidine triple therapy is a useful H. pylori eradication regimen.

PMID- 8980936
TI  - The outcome of urgent surgery for major peptic ulcer haemorrhage following failed
      endoscopic therapy.
AB  - OBJECTIVE: To review the outcome of patients who underwent emergency surgery for
      major peptic ulcer haemorrhage after failed endoscopic therapy. To address
      whether 'conservative' or 'aggressive' surgery is best. DESIGN: A retrospective
      analysis of emergency surgery for ulcer bleeding which could not be controlled by
      endoscopic therapy. SETTING: The four admitting units in the Lothian region of
      Scotland. PARTICIPANTS: Sixty-seven patients who failed endoscopic therapy for
      bleeding peptic ulcer and underwent emergency surgery between December 1990 and
      December 1995. Simple underrunning or excision of ulcer alone was done in 31
      patients whilst 36 had more radical surgery. MAIN OUTCOME MEASURES: Rebleeding
      and 30-day mortality rates. RESULTS: Rebleeding was significantly higher in
      patients treated by underrunning (7 versus 1, P < 0.013). There were fewer deaths
      in the radically treated group (5 versus 7, not significant). CONCLUSION:
      Patients undergoing surgical operation for severe peptic ulcer haemorrhage after
      failed endoscopic therapy may be best served by a relatively aggressive approach.

PMID- 8980937
TI  - Long-term therapy with sulphasalazine protects against colorectal cancer in
      ulcerative colitis: a retrospective study of colorectal cancer risk and
      compliance with treatment in Leicestershire.
AB  - OBJECTIVES: The aims of this study were to (i) estimate the prognosis of a 10
      year cohort as expressed by risk of colectomy and risk of development of
      colorectal cancer, and (ii) assess the impact of long-term sulphasalazine on the
      natural course of ulcerative colitis. PATIENTS: One hundred and seventy-five
      patients diagnosed between 1972 and 1981 with either total colitis (n = 143) or
      with limited ulcerative colitis but deceased (n = 32) were identified. Overall
      there was 98% case ascertainment and verification. RESULTS: A total of 49
      patients underwent a colectomy, 6 as emergency laparotomies, 36 for failed
      medical management and 7 for known colorectal cancer, giving a crude colectomy
      rate of 23.2%. The colectomy rate was 7.2% in the year of diagnosis, decreasing
      in frequency over the next 4 years, then reaching a steady state of approximately
      1.7% per year. In the total cohort, colorectal cancer occurred in 10 patients
      within the study period. The cumulative incidence of colorectal cancer 10 years
      after diagnosis was 2.1% and at 20 years 7.4% for the total group of patients
      excluding those with a colectomy. The mean duration of ulcerative colitis before
      diagnosis was 7.9 years (range 5-12). The crude proportions developing cancer
      were 5/152 (3%) in the group who took long-term sulphasalazine but 5/16 (31%) in
      the those who had had their treatment stopped or who did not comply with therapy.
      This is highly significant using a simple chi 2 test (chi 2 = 20.2, df = 1, P <
      0.001). Two methods were used for survival analyses, the log-rank and the
      generalized Wilcoxon methods. Both give highly significant values for the crude
      effect of compliance (P < 0.001). CONCLUSION: Patients with ulcerative colitis
      who were not on long-term sulphasalazine or 5-aminosalicylic acid therapy (either
      because a doctor stopped it or they did not comply with treatment) were
      significantly more likely to develop colorectal cancer than their compliant
      counterparts.

PMID- 8980938
TI  - Tonsillectomy and inflammatory bowel disease location.
AB  - OBJECTIVE: Epidemiological studies have found an increased frequency of childhood
      infections and tonsillectomies in patients with inflammatory bowel disease (IBD).
      The aim of our study was to test whether particular clinical patterns of IBD
      could be associated with previous tonsillectomy. METHODS: Two hundred and twenty
      consecutive IBD patients (100 with Crohn's disease (CD) and 120 with ulcerative
      colitis (UC)) were prospectively assessed and classified into groups according to
      disease location. In those with a positive history of tonsillectomy, an ear, nose
      and throat (ENT) examination was carried out to confirm the diagnosis. RESULTS:
      Eighty-two IBD patients (37%) underwent tonsillectomy in childhood: 47 out of 100
      CD patients (47%), and 35 out of 120 UC patients (29%). Disease location in CD
      patients affected the ileum in 28, and 21 of them were tonsillectomized
      (tonsillectomy rate of 75%). Thirty-six patients had an ileocolonic location, and
      14 of them had had a tonsillectomy (39%). With disease confined to the colon,
      only 9 out of 29 patients (31%) had undergone previous tonsillectomy. The higher
      prevalence of tonsillectomy in patients with CD ileitis was statistically
      significant (P = 0.0034). No significant differences between groups of UC
      patients according to the extent of the disease were found. CONCLUSION: The ileum
      is the most prevalent location of disease in CD patients with previous
      tonsillectomy.

PMID- 8980939
TI  - The endoscopic picture reflects transmural inflammation better than endoscopic
      biopsy in Crohn's disease.
AB  - OBJECTIVE: To investigate how the histopathological picture of endoscopic biopsy
      specimens related to that of transmural sections and also how these related to
      the endoscopic findings. DESIGN: Prospective controlled study. PATIENTS AND
      METHODS: Intraoperative endoscopy was performed on 19 patients with Crohn's
      disease and mucosal biopsies were obtained from various bowel segments that were
      to be resected. The histopathological appearance of mucosal biopsies was compared
      to that of transmural bowel sections and to endoscopic findings. Ten patients
      undergoing surgery for colonic cancer were used as controls. RESULTS: Poor
      agreement was found between the pathologist's assessment of biopsy specimens and
      transmural bowel sections (kappa < 0.38) for all histological variables. The
      endoscopic assessment of inflammatory severity had a better correlation with
      global histological assessment of transmural bowel wall sections (r = 0.75) than
      with a global histological assessment of endoscopic biopsy specimens (r = 0.65).
      CONCLUSION: Endoscopic assessment of inflammation in Crohn's disease better
      reflects transmural histopathology than mucosal biopsy and thus the severity and
      extent of inflammation. Routine biopsy sampling is of limited value in Crohn's
      disease.

PMID- 8980940
TI  - Value of technetium-99m HMPAO-labelled leucocyte scintigraphy as an initial
      screening test in patients suspected of having inflammatory bowel disease.
AB  - OBJECTIVE: This study was designed to evaluate the role of technetium-99m (99mTc)
      hexamethyl propylene amine oxime (HMPAO)-labelled leucocyte imaging as an initial
      screening test in patients suspected of having inflammatory bowel disease (IBD).
      PATIENTS AND METHODS: Thirty-one patients in whom a final diagnosis of irritable
      bowel syndrome (IBS) was made (group 1) and another 33 patients with established
      Crohn's disease (group 2) were studied. All patients had 99mTc HMPAO-labelled
      leucocyte scan with imaging at 40 and 120 min. Scans with abnormal bowel uptake
      were considered positive and this uptake was quantified by visual grading and
      computer-based methods (scan score). Group 1 patients with positive 99mTc HMPAO
      scan underwent an indium-111 (111In)-labelled leucocyte scan (imaging at 180 min)
      followed by endoscopy and barium radiology as deemed necessary in order to verify
      the 99m Tc HMPAO result. RESULTS: Three scan patterns were seen: well localized
      and unequivocally positive scans at both 40 min and 2 h were obtained from 28
      patients. All but one had established Crohn's disease. Diffuse bowel uptake was
      seen in 14 scans. Ten of these (false positive) were obtained from symptomatic
      patients with IBS and four (false negative) from patients with asymptomatic
      Crohn's disease. No bowel uptake at 40 min and 2 h was seen in 22 scans. All but
      two of these (who had quiescent Crohn's disease) were obtained from patients with
      IBS. Active Crohn's disease is associated with significantly higher scan score
      (mean +/- SEM, 82.1 +/- 13.6) than the false positive scans (12.5 +/- 3.1, P > or
      = 0.001). Patients with false positive 99mTc HMPAO scans had negative 111In
      scans, endoscopy and barium radiology. CONCLUSION: Bowel scanning using either
      111In or 99mTc HMPAO is useful in excluding active IBD. Because of radiation
      dose, image quality and availability 99mTc may be preferred to 111In.

PMID- 8980941
TI  - High prevalence of adenomas and microadenomas of the duodenal papilla and
      periampullary region in patients with familial adenomatous polyposis.
AB  - BACKGROUND: Patients with familial adenomatous polyposis (FAP) are traditionally
      considered to be at high risk for duodenal-papillary and periampullary adenomas
      and cancer. AIM: To evaluate prospectively the prevalence, histology and clinical
      significance of ampullary and periampullary macroscopic and microscopic lesions
      in our population of affected patients. SETTING: Three gastroenterological
      departments of northern Italian hospitals. PATIENT AND METHODS: Twenty-five
      affected patients were carefully investigated over a 24-month period by end
      viewing and side-viewing upper panendoscopy. Biopsies were performed on
      representative macroscopic lesions and randomly on normal-appearing papillary and
      periampullary mucosa. RESULTS: Seven patients had macroscopic adenomas of the
      duodenal papilla, three of the periampullary region and five at both sites
      (cumulative prevalence 40%). An additional six patients had macroadenomas in the
      rest of the duodenum (overall prevalence 64%). Microscopic adenomas were
      identified in nine and two patients in the papilla and periampullary region,
      respectively, and in three at both sites (overall prevalence 44%). Thus, a total
      of 17 (68%) patients presented macro- or microadenomas at these locations. The
      prevalence rose to 72%, when a further patient with macroadenomas in the rest of
      the duodenum only was included. Malignancy was not encountered and severe
      dysplasia was observed only in a macroadenoma of the second duodenal portion. A
      higher frequency of macroadenomas in the papilla and periampullary region was
      significantly correlated with the presence and number of such lesions in the rest
      of the duodenum (P = 0.04). No other significant association was detected either
      between micro- or macroadenomas at different sites or with the demographic,
      clinical and pathological features. CONCLUSION: This study confirms that the
      duodenal papilla and periampullary region are sites with high prevalence of macro
      and microscopic adenomas in patients with FAP. However, our data do not seem to
      support a higher frequency and malignancy potential of such lesions as compared
      to polyps in the rest of the duodenum. Nevertheless, these findings warrant a
      periodic, careful examination of the duodenum with either end-viewing or side
      viewing endoscopy, the need for random biopsies of the papilla and periampullary
      region and the removal of any larger or rapidly growing lesions detected.

PMID- 8980942
TI  - Decreased substance P levels in rectal biopsies from patients with slow transit
      constipation.
AB  - OBJECTIVE: Previous studies in patients with chronic constipation found
      abnormalities in the nervous tissue of the large intestine, predominantly in the
      muscularis externa. Since there is evidence that the nervous system of mucosa and
      submucosa is also involved in the control of colonic motility we investigated the
      contents of vasoactive intestinal polypeptide (VIP), somatostatin and substance P
      in rectal biopsies of patients with slow colonic transit constipation. DESIGN AND
      METHODS: Twenty-two patients (17 females, 5 males) with chronic slow transit
      constipation (oro-anal transit with radio-opaque markers on high fibre diet > 70
      h) and long-term use of laxatives, and 20 controls (12 females, 8 males) with no
      history of constipation, were included in this study. Large rectal biopsy
      specimens including the submucosa were obtained from 5 cm above the dentate line
      and frozen in liquid nitrogen. After microdissection of the biopsies into mucosa
      and submucosa the neuropeptides were extracted by boiling and homogenizing the
      tissue in acetic acid and determined using validated radioimmunoassays. RESULTS:
      Patients with slow transit constipation showed, compared to healthy controls,
      significantly lower levels of the excitatory neurotransmitter substance P in the
      mucosa and submucosa of rectal biopsies. There was no difference between the two
      groups concerning the levels of the inhibitory neurotransmitters, VIP and
      somatostatin. CONCLUSION: Slow transit constipation is associated with
      abnormalities of the substance P content of the enteric nervous system of mucosa
      and submucosa. This seems not to be related to chronic laxative use, since
      anthranoids cause a reduction in the levels of inhibitory neurotransmitters (VIP,
      somatostatin), but not of substance P, in the rat colon.

PMID- 8980943
TI  - Gallbladder cancer with a low junction of the cystic duct or an anomalous
      pancreaticobiliary junction.
AB  - OBJECTIVE: To evaluate conditions similar to those of carcinogenesis of the
      gallbladder between the gallbladder with a low junction of the cystic duct (LJCD)
      and an anomalous pancreaticobiliary junction (APBJ). DESIGN: Retrospective and
      clinicopathological analysis of patients with gallbladder carcinoma. SETTING:
      First Department of Surgery, Kansai Medical University. PATIENTS: Examination of
      47 patients (7 men and 40 women; average age: 67.8 years) with gallbladder
      carcinoma revealed 7 patients (14.9%; 1 man and 6 women; average age: 67.8 years)
      with LJCD and 6 patients (12.8%; 6 women; average age: 60.3 years) with APBJ.
      METHODS: Clinical findings in both groups were compared with those of the 34
      patients who remained after exclusion of the data of the above 7 patients with
      LJCD and 6 patients with APBJ. The data of the three groups were examined by the
      chi 2 test at the 5% level of significance. RESULTS: Most of the gallbladder
      cancer patients with LJCD or APBJ had gallstones. The biliary amylase levels
      determined in the gallbladder of patients with LJCD or APBJ were remarkably high.
      CONCLUSION: The results indicate that patients with LJCD or APBJ are more likely
      to develop carcinoma of the gallbladder. The factors responsible for
      carcinogenesis may be alteration of the bile content due to reflux of pancreatic
      enzymes through the LJCD or APBJ, and mechanical irritation due to gallstones.
      Therefore, these pathological conditions in patients with LJCD are similar to
      those experienced in patients with APBJ.

PMID- 8980944
TI  - Campylobacter jejuni peritonitis in a patient with liver cirrhosis.
AB  - A 56-year-old man with alcoholic liver cirrhosis (Child-Pugh class C), ascites
      and hepatocellular carcinoma developed acute diarrhoea and fever. Ascites
      granulocyte count was 5760 per microliters. Campylobacter jejuni grew in cultures
      from faeces, blood and ascites. The patient was successfully treated with
      erythromycin. Although the incidence of bacterial infections including
      peritonitis is high in patients with end-stage liver cirrhosis, this is one of
      very few cases in which Campylobacter jejuni has been identified as the causative
      microorganism.

PMID- 8980945
TI  - Mesenteric arteriovenous fistula causing portal hypertension and bleeding
      duodenal varices.
AB  - We report a case of portal hypertension associated with a non-traumatic
      arteriovenous fistula, presenting with bleeding duodenal varices. The patient was
      admitted for melaena. Emergency endoscopy showed oesophageal varices with no
      signs of recent bleeding and with no blood in the upper gastrointestinal tract.
      Arteriography of the coeliac axis and superior mesenteric artery failed to detect
      any bleeding source. Endoscopy was repeated because of persistent bleeding and
      revealed active bleeding from varices in the distal duodenum. The patient
      underwent surgery and a large paraduodenal varicose vein associated with an
      arteriovenous fistula was found. Resection of the paramural varix and surgical
      occlusion of the arteriovenous fistula were effective in the control of bleeding.
      Liver biopsy revealed mild portal fibrosis without cirrhosis. Three years after
      surgery the patient still has oesophageal varices but has not had recurrent
      bleeding. There was regression of intraduodenal varices.

PMID- 8980946
TI  - Herbs--useful plants. Their role in history and today.

PMID- 8980947
TI  - Conscious sedation for endoscopy.

PMID- 8980948
TI  - Induced sputum to assess airway inflammation in asthma.

PMID- 8980949
TI  - Eosinophils in eosinophilic pneumonia.

PMID- 8980950
TI  - Lung hyperinflation in airway obstruction.

PMID- 8980951
TI  - Repeatability of cellular and soluble markers of inflammation in induced sputum
      from patients with asthma.
AB  - Sputum induced by inhalation of nebulized hypertonic saline is increasingly used
      to monitor airways inflammation in asthma. The aim of this study was to assess
      the repeatability of measuring cellular and soluble markers of inflammation in
      whole sputum samples as obtained by sputum induction in patients both with mild
      and moderate-to-severe asthma. Twelve patients with mild, atopic asthma without
      inhaled steroid treatment and nine patients with moderate-to-severe, atopic
      asthma treated with inhaled steroids were studied on two separate days at least 2
      days apart. Whole sputum samples, induced by inhalation of hypertonic (4.5%)
      saline, were homogenized, and analysed for differential cell counts and for
      concentrations of albumin, fibrinogen, interleukin-8 (IL-8), and eosinophil
      cationic protein (ECP). Repeatability was expressed as intraclass correlation
      coefficient (Ri), and as coefficient of repeatability (CR) in percentage cells or
      in doubling concentration. Samples from two patients with mild asthma contained
      more than 80% squamous cells and were excluded from analysis. The repeatability
      for cell differential counts in both groups combined was: for neutrophils, Ri =
      0.57 and CR = 31.0; for eosinophils, Ri = 0.85 and CR = 12.4; and for
      lymphocytes, Ri = 0.76 and CR = 6.9. The repeatability of the fluid phase
      measurements was: for albumin, Ri = 0.71 and CR = 3.2; for fibrinogen, Ri = 0.88
      and CR = 2.8; for IL-8, Ri = 0.66 and CR = 2.2; and for ECP, Ri = 0.82 and CR =
      1.1. We conclude that the repeatability of cellular and soluble markers of
      inflammation in induced sputum from patients with mild and moderate-to-severe
      asthma is satisfactory. Hence, induced sputum, processed by using the whole
      expectorated sample, seems to be a valuable method to monitor airway inflammation
      in asthma.

PMID- 8980952
TI  - Comparison of two methods of collecting induced sputum in asthmatic subjects.
AB  - The method that we have previously reported for sputum induction involves
      collecting the entire expectorate produced over a 20 min inhalation of 3% saline
      aerosol. This method presents the potential disadvantage of a considerable and
      variable salivary contribution to the induced sputum sample. In this study, we
      examined whether separate collection of saliva and sputum represents a better
      method for collecting induced sputum during sputum induction. In 11 stable
      asthmatics, we compared the volume, total and differential cell counts, and
      eosinophil cationic protein (ECP) levels in four induced sputum samples, two
      performed using our previous method (Method A) and two using another method
      (Method B) in which subjects spit saliva into one container before coughing
      sputum into another. We found that the volume of sputum obtained with Method B
      was lower than that obtained with Method A (6.16 +/- 0.61 vs 20.1 +/- 2.7 mL; p =
      0.003), as was the percentage of squamous cells (34 +/- 4 vs 47 +/- 6; p =
      0.023). In addition, the ECP levels in samples collected by Method B were higher
      (261 +/- 42 vs 145 +/- 26 ng.mL-1; p = 0.01). The differential counts of
      nonsquamous cells were similar except for the percentage of neutrophils, which
      was lower in Method B (37 +/- 4 vs 50 +/- 5%; p = 0.019). The repeatability of
      measurements of eosinophil percentages and of ECP levels was similar for the two
      methods. We conclude that separate collection of saliva and sputum yields induced
      sputum samples with reduced amounts of saliva and is, therefore, a better method
      for collecting induced sputum.

PMID- 8980953
TI  - Increased expression of mRNA encoding RANTES and MCP-3 in the bronchial mucosa in
      atopic asthma.
AB  - The selective recruitment of eosinophils into the mucosal lining of the airways
      is a prominent feature of atopic asthma, and is believed to be an important
      component in the disease pathogenesis. The precise stimuli responsible for the
      influx of eosinophils remain unclear. Using a semiquantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) technique, the numbers of copies
      (relative to the "housekeeping" gene beta-actin) of messenger ribonucleic acid
      (mRNA) encoding the eosinophil-active chemotactic cytokines, the factor regulated
      upon activation in normal T-cells expressed and secreted (RANTES) and monocyte
      chemotactic protein-3 (MCP-3), was measured in bronchial biopsies from atopic
      asthmatic patients (n = 9), and compared with atopic nonasthmatic (n = 8) and
      nonatopic nonasthmatic (n = 8) control subjects. In addition, further biopsies
      from each subject were prepared for immunohistochemistry and the numbers of
      activated (EG2+) eosinophils measured. The expression of RANTES mRNA was
      significantly elevated in the atopic asthmatic group as compared to the atopic
      nonasthmatic controls (p = 0.013) and the nonatopic nonasthmatic controls (p =
      0.007). Similarly, the expression of mRNA encoding MCP-3 was significantly
      elevated in the atopic asthmatic group, relative to the atopic nonasthmatic
      controls (p = 0.014) and the nonatopic nonasthmatic control group (p = 0.011).
      Elevated RANTES and MCP-3 mRNA expression was associated with significantly
      increased numbers of bronchial mucosal eosinophils in the atopic asthmatic
      patients as compared to the atopic nonasthmatic (p = 0.03) and nonatopic
      nonasthmatic (p = 0.006) control subjects. In conclusion, we have identified
      elevated expression of messenger ribonucleic acid encoding RANTES and monocyte
      chemotactic protein-3 in the bronchial mucosa of atopic asthmatic patients
      relative to controls. These findings are compatible with the hypothesis that
      eosinophil-active beta-chemokines play a role in the mechanism of eosinophil
      recruitment to the asthmatic bronchial mucosa.

PMID- 8980954
TI  - Effect of frusemide on Cl- channel in rat peritoneal mast cells.
AB  - Frusemide can be used as an antiasthma drug and appears to inhibit the release
      (conditioned by activation of Cl- channels) of mast cell proinflammatory
      mediators. We studied the cause of the effects of frusemide, checking its action
      on Cl- channels. The patch-clamp technique was used to study single-channel
      currents, and differences in electrical potential of the cellular membrane of rat
      peritoneal mast cells were measured. In inside-out configuration, outwardly
      rectifying Cl- channels were identified whose conductance was 2.4/1.7 pS at
      positive and negative voltages. In cell-attached configuration, the open
      probability (Po) of the channel increased with depolarization or with the
      presence of cyclic adenosine monophosphate (cAMP) in the incubation medium. Po
      increased with a rise of cytoplasmic free calcium concentration [Ca2+] and was
      inhibited by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and by 4-4'
      diisothiocyanatoostilbene-2-2'-disulphonic acid (DIDS). These channels seem to be
      the main cause of mast cell Cl- conductance. Frusemide (10(-5) and 10(-3) M) did
      not affect Cl- channel activity when using excised patches. In cell-attached
      configuration experiments, the presence of frusemide (from 10(-5) to 10(-3) M) in
      the cell incubation medium, increasingly reduced Po (median inhibitory
      concentration (IC50) = 4.3 x 10(-7) M). In similar conditions, bumetanide also
      inhibited Po (IC50 = 5.7 x 10(-3) M). The results of this study suggest that
      frusemide can inhibit mast cell Cl- channels only via an indirect mechanisms,
      which probably involves an inhibition of a Na(+)-K(+)-2Cl- symport.

PMID- 8980955
TI  - Role of thromboxane-A2 and cholinergic mechanisms in bronchoconstriction induced
      by cigarette smoke in guinea-pigs.
AB  - Acute exposure to cigarette smoke provokes bronchoconstriction and increases the
      concentration of thromboxane (Tx) A2 in bronchoalveolar lavage (BAL) fluid. The
      purpose of this study was to investigate the role of TxA2 and cholinergic
      mechanisms in the airway response induced by exposure to cigarette smoke in
      guinea-pigs. Anaesthetized animals were exposed to 200 puffs of smoke for 10 min.
      The amount of Evans blue dye extravasated into the bronchial tissue was then
      measured BAL was performed to determine cell counts and the concentration of
      TxB2, a stable metabolite of TxA2. The effects of pretreatment with a Tx synthase
      inhibitor, OKY-046 (10 mg.kg-1), and/or atropine (1 mg.kg-1) were evaluated.
      Exposure to cigarette smoke caused significant bronchoconstriction (284 +/- 33%
      of baseline pulmonary resistance (RL)) and plasma extravasation (30.0 +/- 3.8 vs
      16.8 +/- 2.6 ng.mg-1 of sham control; main bronchi). OKY-046 or atropine
      significantly inhibited the bronchoconstriction to a similar extent, without
      affecting the plasma extravasation. Combined use of these compounds had no
      additive effect. The cigarette smoke caused significant increase in TxB2 (48 +/-
      10 vs 14 +/- 1 pg.mL-1 of sham control) in BAL fluid, which was abolished by OKY
      046 but not by atropine. The cellularity in BAL fluid was not different among
      groups. These results suggest that the bronchoconstriction induced by cigarette
      smoke is partially mediated by thromboxane A2, which is dependent on a
      cholinergic pathway.

PMID- 8980956
TI  - Modified epithelial cell distribution in chronic airways inflammation.
AB  - Although airway epithelium is known to be modified during chronic respiratory
      diseases, epithelial cells have rarely been precisely quantified. We therefore
      intended to evaluate epithelial cell distribution in inflammatory airways, using
      a cytological approach. Nasal airway cells in 12 patients with nonallergic
      chronic rhinitis were sampled by brushing, quantified after cytocentrifugation
      and compared to those from eight controls. Cell populations were quantified after
      May-Grunwald Giemsa staining and alpha-tubulin immunolabelling to demonstrate
      ciliary differentiation. When compared to controls, rhinitis patients exhibited
      lower percentages of ciliated cells (59 +/- 4 versus 32 +/- 2%, respectively),
      and higher percentages of goblet (24 +/- 3 versus 37 +/- 2%) and basal cells (9
      +/- 1 versus 18 +/- 2%). After tubulin immunolabelling, positive staining was
      specifically detected in cells with cilia (LC+), and in the cytoplasm of some
      small round cells without obvious cilia (LC-). Fewer immunolabelled cells were
      detected in rhinitis patients than in controls (with significantly lower
      percentages of LC+ and higher percentages of LC-). Nasal brushing is an effective
      technique for quantification of airway epithelial cells. Tubulin immunolabelling
      is useful to detect ciliated cells and distinguishes another cell population,
      possibly preciliated cells. These cytological findings suggest the presence of
      modifications of epithelial differentiation and proliferation, possibly related
      to local chronic inflammation.

PMID- 8980957
TI  - Videomicroscopy of methacholine-induced contraction of individual airways in
      precision-cut lung slices.
AB  - Contraction of airways of different size can be studied in viable lung slices by
      videomicroscopy. However, at present, application of this technique is limited by
      the heterogeneous responses obtained. We investigated the use of precision-cut
      lung slices to examine contraction of individual airways. Lung slices of 250 +/-
      20 microns were prepared from Wistar rats and cultured in a roller incubator in
      serum-free minimum essential medium (MEM). Under these conditions, the slices
      were viable for at least 70 h, as indicated by leakage of lactate dehydrogenase
      into the supernatant, thymidine incorporation and ciliary beating. The slices
      were placed in a newly developed incubation chamber and mounted by a nylon thread
      that was fixed to a platinum wire. The whole chamber was positioned on a
      microscope stage, and contraction of single airways was followed under a
      microscope that was coupled to a CCD-camera. Reduction in airway area was taken
      as an index of bronchoconstriction and was determined by a computer program.
      Addition of methacholine resulted in a concentration-dependent (concentration
      producing half the maximal effect (EC50) = 0.64 +/- 0.08 (mean +/- SD) microM; n
      = 64) contraction of single airways. In the presence of hydrocortisone, the EC50
      was about six times greater, i.e. 3.7 +/- 0.9 microM (n = 7), and the effect of
      the steroid was largely abolished by propanolol (EC50 = 1.1 +/- 0.1 microM; n =
      7). Airways with an area smaller than 35,000 microns2 were nearly nine times more
      sensitive to methacholine (EC50 = 0.1 +/- 0.03 microM; n = 20) than larger ones
      (EC50 = 87 +/- 0.27 microM; n = 22). We conclude that cultured precision-cut lung
      slices are a useful model for routine study of contraction of individual airways
      of various sizes. The measurements were precise and reproducible and showed that
      smaller airways are more sensitive to methacholine than larger ones.

PMID- 8980958
TI  - Eosinophil cationic protein and immunoglobulin levels in bronchoalveolar lavage
      fluid obtained from patients with chronic eosinophilic pneumonia.
AB  - In chronic eosinophilic pneumonia (CEP), histopathological evidence exists for
      the degranulation of eosinophils and the release of various toxic proteins. In
      vitro studies have demonstrated the degranulation of eosinophils in response to
      aggregated and complexed immunoglobulins. The aims of this study were to
      investigate: 1) whether the eosinophil cationic protein (ECP) and immunoglobulin
      (Ig) levels in bronchoalveolar lavage (BAL) fluid from patients with CEP are
      increased compared to those of healthy controls; 2) and whether a relationship is
      present between immunoglobulin levels and ECP levels in BAL fluid from patients
      with CEP. The BAL from 12 patients with CEP was selected, retrospectively, from
      all BAL analyses performed in our centre between 1986 and 1992. ECP levels were
      measured using a radioimmunoassay in BAL fluid of patients with CEP and 10
      healthy controls. ECP levels and immunoglobulin levels in BAL fluid from patients
      with CEP were found to be elevated compared to controls (p < 0.001). A
      relationship was found between IgA levels and ECP levels in BAL fluid from
      patients with CEP (r = 0.72; p = 0.043). In conclusion, eosinophil cationic
      protein and immunoglobulin levels were found to be increased in bronchoalveolar
      lavage fluid from patients with chronic eosinophilic pneumonia. The relationship
      found between immunoglobulin A levels and eosinophil cationic protein levels may
      suggest that immunoglobulin A could be involved in the degranulation of
      eosinophils in chronic eosinophilic pneumonia.

PMID- 8980959
TI  - Adhesion molecule expression on eosinophils in idiopathic eosinophilic pneumonia.
AB  - Idiopathic eosinophilic pneumonia (IEP) is characterized by the accumulation of
      eosinophils in the alveolar spaces and the interstitium of the lung, frequently
      accompanied by peripheral eosinophilia. To clarify the roles of adhesion
      molecules of eosinophils in the pathogenesis of eosinophilic pneumonia, we
      analysed their expression by eosinophil and T-lymphocyte populations in
      peripheral blood and bronchoalveolar lavage fluid (BALF) obtained from 11
      patients with eosinophilic pneumonia, using flow cytometric methods. Cell
      differentials in BALF showed increased numbers of eosinophils, the increase
      correlating with the number of activated T-lymphocytes in BALF. The expressions
      of CD11a (lymphocyte function-associated antigen-1 (LFA-1)), CD11b (Mac-1), CD18,
      CD49d (very late activation antigen-4 (VLA-4)), and CD62L (L-selectin) by
      eosinophils in BALF were all lower than those of eosinophils in peripheral blood.
      In contrast, CD54 (intercellular adhesion molecule-1 (ICAM-1)) was expressed by
      eosinophils in BALF, but not by those in peripheral blood. These results indicate
      that intercellular adhesion molecule-1 expression by eosinophils in
      bronchoalveolar lavage fluid but not in peripheral blood may be induced by
      locally activated T-cells or macrophages and may be important in the pathogenesis
      of idiopathic eosinophilic pneumonia.

PMID- 8980960
TI  - Diverse cellular TGF-beta 1 and TGF-beta 3 gene expression in normal human and
      murine lung.
AB  - A role for transforming growth factor-beta 1, (TGF-beta 1) has been proposed in
      lung development and in the pathogenesis of pulmonary disease. However, previous
      studies have not delineated the cells expressing TGF-beta 1 in normal adult lung,
      nor compared its gene expression with that of other TGF-beta isoforms. We used
      digoxigenin-labelled riboprobes to localize TGF-beta 1 and TGF-beta 3 gene
      expression in normal adult human and mouse lung. This procedure was technically
      simple, providing excellent resolution. TGF-beta 1 and TGF-beta 3 messenger
      ribonucleic acid (mRNA) transcripts were detected in a wide variety of cells. In
      human lung, mRNA for both isoforms was localized to bronchiolar epithelium and
      alveolar macrophages. TGF-beta 1, but not TGF-beta 3 mRNA was detected in
      mesenchymal and endothelial cells. In murine tissue, TGF-beta 1, mRNA was
      localized to bronchiolar epithelium, Clara cells, mesenchymal cells, pulmonary
      endothelium and alveolar cells, including macrophages. TGF-beta 3 mRNA was
      similarly distributed but not detected in endothelium. In summary, using a
      nonisotopic technique in lung tissue, we have detailed the cells expressing the
      transforming growth factor-beta 1 and beta 3 genes in human and murine lung.
      There was widespread expression of these cytokines in normal lung consistent with
      autocrine or paracrine roles in regulating cellular turnover, immune defence and
      matrix protein metabolism.

PMID- 8980961
TI  - Proinflammatory effect of Pediococcus pentosaceus, a bacterium used as hay
      preservative.
AB  - Bacterial cultures, such as Pediococcus pentosaceus, are used to treat hay with
      the objective of preventing hay heating and moulding, and thus, the development
      of the microbial growth which causes farmer's lung. The aim of this study was to
      investigate whether such bacterial cultures have the potential to induce a
      pulmonary inflammatory response. Mice were instilled 3 days week-1 for 3 weeks
      with either saline or nonviable preparations of P. pentosaceus, Saccharopolyspora
      rectivirgula, Lactococcus lactis (control bacteria) or with the combinations of
      S. rectivirgula and P. pentosaceus. P. pentosaceus induced a significant
      inflammatory response in the lung which was similar to that produced by S.
      rectivirgula. L. lactis produced a response of a lower intensity. The total
      number of cells in bronchoalveolar lavage were: S. rectivirgula: 6.4 x 10(5)
      cells.mL-1; P. pentosaceus: 4.3 x 10(5) cells.mL-1; S. rectivirgula + P.
      pentosaceus: 5.4 x 10(5) cells.mL-1, L. lactis: 6.8 x 10(5) cells.mL-1 and saline
      group 3.7 x 10(4) cells.mL-1. The lung index was higher in S. rectivirgula+P.
      pentosaceus and P. pentosaceus groups than in S. rectivirgula, L. lactis and
      saline groups. The quantity of specific immunoglobulin G and A (IgG and IgA) to
      P. pentosaceus and L. lactis levels (in the blood and/or lavage fluid) were
      similar to those against S. rectivirgula. In mice, P. pentosaceus has the
      potential to induce a similar inflammatory response in the lung as S.
      rectivirgula, which is the most common antigen responsible for farmer's lung
      disease in Quebec. Further studies are needed to verify whether farmers can
      develop farmer's lung or other lung responses to this new potential antigen.

PMID- 8980962
TI  - The diagnostic value of bronchoalveolar lavage and transbronchial lung biopsy in
      cryptogenic organizing pneumonia.
AB  - In order to determine the diagnostic value of bronchoalveolar lavage (BAL) and
      transbronchial lung biopsy (TBLB) in cryptogenic organizing pneumonia (COP) a
      prospective study was carried out. Thirty seven consecutive patients (20 males
      and 17 females) with clinicoradiological features of COP were enrolled in the
      study. The statistical analyses were completed in 35 cases. Twenty eight patients
      were diagnosed to have COP, all of them with a confirmatory biopsy. In seven
      cases, a different diagnosis was made. BAL cytological and phenotypical criteria
      considered for the diagnosis of COP were: a lymphocytosis of more than 25% (with
      a CD4/CD8 ratio less than 0.9); combined with at least two of the following data
      (foamy macrophages of > 20%, and/or neutrophils of > 5%, and/or eosinophils of >
      2% and < 25%). TBLB specimens were classified as positive for COP if they showed:
      buds of granulation tissue within the centrilobular air spaces; infiltration of
      alveolar walls with chronic inflammatory cells; and preservation of alveolar
      architecture. BAL was performed in 34 patients; 17 cases were consistent with the
      final diagnosis of COP (sensitivity 63%), and four cases were correctly
      classified as negative (specificity 57%). BAL had a positive predictive value
      (PPV) of 85% and a negative predictive value (NPV) of 29%. TBLB was performed in
      32 patients; it correctly identified COP in 16 cases (sensitivity 64%), and six
      cases were correctly classified as negative (specificity 86%). TBLB had a PPV of
      94% and a NPV of 40%. The accuracy of the examinations, that is the probability
      of correctly diagnosing both diseased and nondiseased patients by BAL or TBLB,
      was 62 and 69%, respectively. Our findings suggest that the combination of
      cytological bronchoalveolar lavage and histological transbronchial lung biopsy
      data obtained during a fibreoptic procedure appears to be an effective method for
      the initial investigation in cryptogenic organizing patients pneumonia presenting
      with patchy radiographic shadows.

PMID- 8980963
TI  - Oxidant-antioxidant balance in alveolar macrophages from newborn rats.
AB  - An oxidant-antioxidant imbalance in neonatal alveolar macrophages (AMs) may
      contribute to the increased susceptibility to lung injury described in the
      neonatal period. We therefore evaluated oxygen radical production by rat AMs at
      various postnatal ages, and measured in parallel cellular antioxidant enzyme
      activities. AMs were obtained by bronchoalveolar lavage from rats aged < 24 h, 21
      days and 5 weeks, and results were compared to those obtained with adult rat AMs.
      Intracellular production of oxygen radical species, estimated fluorometrically
      using 2',5'-dichlorofluorescein diacetate as the substrate, was significantly
      reduced in neonates as compared with adults, both in the presence and in the
      absence of cell stimulation with phorbol myristate acetate (PMA) or opsonized
      zymosan. A similar pattern was observed for the extracellular release of oxygen
      radical species, evaluated by lucigenin-enhanced chemiluminescence (CL) or
      peroxidase-catalysed CL oxidation of luminol: peak CL values measured after cell
      stimulation with PMA or opsonized zymosan remained significantly lower for AMs
      from newborn rats than for AMs from adults. By contrast, high values for
      antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase)
      in AMs were demonstrated in newborns as compared to adults. We conclude that high
      antioxidant activity in rat AMs after birth may be at least partly responsible
      for the low production of oxygen metabolites observed during the same period.

PMID- 8980964
TI  - Surfactant apoprotein-A concentration in airway secretions for the detection of
      pulmonary oedema.
AB  - Patients with cardiogenic pulmonary oedema expectorate foamy sputum containing
      surfactant, which might be expected to include surfactant apoprotein A (SP-A). SP
      A is specific for lung surfactant. We have measured the SP-A concentration in
      airway secretions to determine whether it is useful in distinguishing pulmonary
      oedema from other disorders. Samples of sputum and of aspirated airway secretion
      were obtained from 11 patients with cardiogenic pulmonary oedema, seven patients
      with clinically stable congestive heart failure, five patients with adult
      respiratory distress syndrome (ARDS) and 20 control patients (10 intubated) with
      other respiratory diseases. The samples were used for the measurement of SP-A
      concentration by a two-site simultaneous immunoassay with monoclonal antibodies
      against SP-A. SP-A concentrations, measured in samples of sputum and aspirated
      secretions, depended on the diagnosis of the patients from which they had come.
      In descending order these samples came from patients with: cardiogenic pulmonary
      oedema (1324 +/- 197 micrograms.mL-1; n = 33); ARDS (311 +/- 47 micrograms.mL-1;
      n = 23); clinically stable congestive heart failure (78 +/- 10 micrograms.mL-1; n
      = 21); and control conditions (3.0 +/- 0.6 micrograms.mL-1; n = 30).
      Concentrations from disease samples did not overlap with controls. In samples
      from patients with cardiogenic pulmonary oedema, the SP-A concentration
      correlated with mean pulmonary capillary wedge pressure (PCWP) (p < 0.001; n =
      39). These findings indicate that the measurement of the surfactant apoprotein A
      concentration in airway secretions may be useful for the detection of pulmonary
      oedema.

PMID- 8980965
TI  - L-NAME aggravates pulmonary oxygen toxicity in rats.
AB  - Exposure to high oxygen concentration leads to acute lung injury and death in
      rats after 72 h. The pathophysiology of this phenomenon relies on several
      mechanisms, including alteration of vascular reactivity, recruitment and
      activation of neutrophils and alveolar macrophages, production of cytokines and
      excess production of free radicals. In addition to its potent vasodilating
      effect, nitric oxide (NO) has also been reported to prevent free radical-mediated
      damage. We wanted to determine whether NG-nitro-L-arginine methyl ester (L-NAME),
      a NO synthase inhibitor, might modulate oxygen toxicity. In rats exposed to
      continuous high oxygen concentration, we studied the effect of administration of
      50 mg.kg-1 of intraperitoneal L-NAME twice a day on the first day of oxygen
      exposure. L-NAME resulted in earlier death, since 57% of the animals exposed to
      oxygen and injected with L-NAME died within 60 h as compared to 22% of the
      animals exposed to oxygen and treated with saline (p < 0.01). Haematocrit and
      bronchoalveolar lavage fluid protein were also significantly increased in animals
      exposed to oxygen and receiving L-NAME. The lung water content was higher in the
      oxygen-exposed groups (p < 0.01) and slightly decreased by L-NAME (p < 0.05).
      Thiobarbituaric acid reactive substances (TBARS) were elevated in plasma (p <
      0.01) and decreased in lung (p < 0.001) of oxygen-exposed animals, but no
      significant effect of L-NAME was observed. NG-nitro-L-arginine methyl ester had a
      deleterious effect in rats exposed to hyperoxia, which might suggest that
      endogenous nitric oxide has a protective role against hyperoxia-induced pulmonary
      lesions.

PMID- 8980966
TI  - Airway nitric oxide in asthmatic children and patients with cystic fibrosis.
AB  - We evaluated the effects of asthma and cystic fibrosis on nitric oxide (NO)
      concentrations in the respiratory tract. NO levels in orally exhaled air and
      nasal gas samples were studied in 90 asthmatic patients (4-14 yrs), 67 patients
      with cystic fibrosis (CF) (5-32 yrs), and 68 controls (4-34 yrs). NO
      concentrations measured by chemiluminescene were correlated with the patient's
      vital capacity, forced expiratory volume in one second (FEV1) and specific airway
      resistance. In all groups, NO concentrations in orally-exhaled air correlated
      with the inhaled ambient NO (r = 0.85-0.91). At an ambient NO concentration of 0
      parts per billion (ppb), asthmatic patients exhaled air with higher NO
      concentrations than cystic fibrosis patients and controls (8.0 +/- 6.1 ppb (n =
      33); 4.9 +/- 2.6 ppb (n = 23); and 3.0 +/- 2.5 ppb (n = 37); respectively; p <
      0.001). Similar results were obtained for ventilation-adjusted orally-exhaled NO.
      Nasal NO concentrations were lower in patients with CF (23 +/- 17 ppb) than in
      controls and asthmatics (96 +/- 47 and 103 +/- 64 ppb; p < 0.001). There was no
      relationship between nasal or oral NO and pulmonary function tests. Our results
      suggest that ambient NO levels influence NO concentrations in orally-exhaled air.
      Like adults, asthmatic children exhale more NO than their controls. Reduced nasal
      NO concentrations in patients with cystic fibrosis may reflect chronic epithelial
      cell damage or an increased mucosal barrier impeding NO diffusion into the
      airway.

PMID- 8980967
TI  - Prevalence of respiratory symptoms, bronchial hyperresponsiveness and atopy among
      adults: west and east Germany.
AB  - The prevalence of respiratory symptoms, atopic sensitization and bronchial
      hyperresponsiveness was compared in a random sample of adults, 20-44 yrs of age,
      in two cities in West and East Germany, Hamburg and Erfurt, respectively. There
      were much higher levels of outdoor air pollution due to sulphur dioxide and
      suspended particulates in Erfurt, and major differences in living conditions
      during the last 40 yrs. Within the European Respiratory Health Survey, a short
      questionnaire was answered by 3,156 (80% response rate) subjects in Hamburg and
      3,272 (74%) in Erfurt. A subset of responders to the short questionnaire
      completed a long questionnaire, spirometry, methacholine or bronchodilator test,
      skin test, and total and specific immunoglobulin E (IgE) measurements, with a
      total number of 1,159 participants in Hamburg and 731 in Erfurt. Six out of 8
      questions on respiratory symptoms and diagnoses were answered in the affirmative
      more frequently in Hamburg than in Erfurt. In Hamburg, mean forced expiratory
      volume in one second (FEV1)% of predicted was 105 vs 107% in Erfurt (p < 0.0001),
      and bronchial hyperresponsiveness was more frequently observed in Hamburg than in
      Erfurt (25 vs 19%; p < 0.05). Atopic sensitization was more prevalent in Hamburg
      than in Erfurt regarding the results of skin tests against grass pollen (24 vs
      19%; p < 0.05), birch pollen (19 vs 8%; p < 0.0005), cat (10 vs 2%; p < 0.0005),
      and Dermatophagoides pteronyssinus (14 vs 10%; p < 0.05). This was reflected by
      the prevalences of positive specific IgE values, which were higher in Hamburg
      than in Erfurt for grass (26 vs 20%; p < 0.05), birch (20 vs 10%; p < 0.0005) and
      cat (12 vs 8%; p < 0.05). In Hamburg, compared to Erfurt, there was: a lower mean
      number of siblings (p < 0.005); a higher degree of childhood and current exposure
      to environmental tobacco smoke (p < 0.005); and a higher frequency of fitted
      carpets and reported mould or mildew inside the house (p < 0.005). Therefore,
      these data may support the hypothesis that childhood factors and exposure to
      indoor allergens and irritants may have been more relevant for the development of
      asthma and atopy than the potential long-term exposure to high concentrations of
      sulphur dioxide and particulate matter.

PMID- 8980968
TI  - Thallium-201 scintigraphy in the evaluation of graft dysfunction in lung
      transplantation. Newark Beth Israel Medical Center Lung Transplant Group.
AB  - The object of this study was to evaluate graft dysfunction utilizing thallium-201
      scintigraphy in patients who had undergone lung transplantation. We studied 11
      patients who had undergone single-lung transplantation and had 44 evaluations for
      suspected graft dysfunction. All evaluations included a lung thallium-201 scan
      and chest radiography. In addition, 42 transbronchial biopsies, 19 gallium-67
      scans and 28 pulmonary function tests were obtained. Rejection was defined by
      histopathology and/or the response to an empirical pulse of methylprednisolone,
      while cultures of protected specimen brushes and blood with a positive chest
      radiograph were used to define infection. The sensitivity of thallium
      scintigraphy for diagnosing rejection and/or infection (94%) was higher than that
      for transbronchial biopsy (86%), gallium scintigraphy (47%), chest radiography
      (67%), or spirometry testing (30%). Specificity was 100% for thallium
      scintigraphy and transbronchial biopsy, as compared to chest radiography and
      spirometry, which were 75 and 80% respectively. This study indicated that
      thallium-201 scintigraphy is useful for screening lung transplant recipients for
      episodes of acute rejection and/or infection. A positive scan is confirmation of
      graft parenchymal dysfunction and may then be followed by empirical treatment or
      bronchoscopy with transbronchial biopsy and culture to differentiate rejection
      and infection.

PMID- 8980969
TI  - Staging of the mediastinum: value of positron emission tomography imaging in non
      small cell lung cancer.
AB  - Recent studies have shown limitations of morphological imaging in staging
      mediastinal lymph node involvement in lung cancer. In contrast to computed
      tomography (CT), which depends primarily on anatomical imaging features, positron
      emission tomography (PET) with 18-fluorodeoxyglucose (FDG) depends mainly on the
      metabolic characteristics of a tissue for the diagnosis of disease. We have
      performed a prospective study comparing FDG-PET and CT of the thorax in the
      presurgical assessment of the mediastinum in 50 patients with newly diagnosed non
      small cell lung cancer (NSCLC). CT and PET scans were interpreted separately, and
      results were compared to pathological staging obtained during thoracotomy. Hilar
      or mediastinal lymph node involvement was present in 58%. In staging for lymph
      node involvement, CT had a sensitivity of 72% and specificity of 81%, whereas PET
      had a sensitivity and specificity of 90% and 86%, respectively. When the PET
      study was compared to histological results, there were four cases showing more
      advanced mediastinal involvement with PET and four cases showing less involvement
      with PET. From our preliminary results, we conclude that positron emission
      tomography with 18-fluorodeoxyglucose is significantly more accurate than
      computed tomography in the mediastinal staging of non-small cell lung cancer.

PMID- 8980970
TI  - Effect of hemithorax irradiation alone or combined with doxorubicin and
      cyclophosphamide in 47 pleural mesotheliomas: a nonrandomized phase II study.
AB  - In order to assess the value of radiotherapy in the treatment of pleural
      mesotheliomas, we studied tumour response and survival after hemithorax
      irradiation alone (RT), or radiotherapy combined with doxorubicin and
      cyclophosphamide chemotherapy (RTCT). Forty seven patients with pleural
      mesotheliomas received irradiation of the diseased hemithorax at 8 MV (megavolt)
      photons to a total dose of 40 Gy, administered in 20 daily fractions of 2 Gy for
      5 days a week. One month after RT, patients aged < or = 70 yrs with a good
      performance status were offered supplementary chemotherapy (CT) with doxorubicin
      30 mg.m-2 body surface on Day 1 and Day 8, combined with cyclophosphamide 600
      mg.m-2 on Day 1, in cycles of 21 days. Tumour response was evaluated by computed
      axial tomography (CAT) before and 1 month after RT and/or CT. Only 3 of the 47
      (95% confidence interval (95% CI)-0.6-13%) irradiated tumours responded with a
      partial response (PR). In 31 patients treated with RT alone, one PR was observed;
      whereas, in the combined treatment group, 2 out of 16 responded with PR to RT. CT
      with doxorubicin and cyclophosphamide induced only 2 out of 16 PRs (95% CI -3.4
      28.4%), and the combined treatment consisting of RT followed by CT induced 2 out
      of 16 PRs. The median survival following the initiation of RT was 7 months in all
      patients (n = 47), 6 months in the RT group (n = 31), and 13 months in the
      combined RTCT group (n = 16). Chest pain, performance status and body weight were
      not favourably affected by the radiotherapy. We conclude that hemithorax
      irradiation of pleural mesotheliomas with a moderately high dose is not useful,
      since it produces no improvement in chest pain, few objective tumour responses
      and no prolongation of survival.

PMID- 8980971
TI  - Pulmonary gas exchange in elderly subjects.
AB  - Although important alterations in structure and function develop with age, the
      hypothesis that the lungs are capable of maintaining adequate gas exchange for
      the maximum human life span is generally accepted. This hypothesis was examined
      by measuring arterial oxygen and carbon dioxide tension (Pa,O2 and Pa,CO2)
      alveolo-arterial differences in oxygen and carbon dioxide tension (PA-a,O2 and Pa
      A,CO2), steady state transfer capacity of the lung for carbon monoxide (TL,CO,ss)
      as well as the gas exchange ratio (R) in a series of 74 healthy subjects aged
      more than 68 yrs (69-104 yrs). In addition, Pa,O2 and Pa,CO2 were measured in a
      series of 55 young healthy subjects, who acted as controls. In the elderly
      subjects, except for TL,CO,ss, there was no significant correlation between any
      of the other variables and age. However, for a given Pa,CO2, Pa,O2 was always
      lower in the group of elderly subjects than in the group of young control
      subjects. TL,CO,ss, as well as TL,CO,ss/minute ventilation (V'k) ratio, was
      correlated with age, according to the following regression equations: TL,CO,ss
      (mL.min-1.kPa-1) = 126-0.90 x age (yrs), and TL,CO,ss/V'k (kPa-1 x 10(3)) = 13.5
      0.085 x age, respectively. These results show that arterial oxygen tension did
      not decrease with age in this series of elderly subjects. However, the decrease
      in steady-state transfer capacity of the lungs for carbon monoxide with age
      indicates that oxygen transport could be diffusion-limited in elderly subjects,
      at least when oxygen consumption is increased.

PMID- 8980972
TI  - Analysis of the double occlusion which provides four pressure gradients.
AB  - The arterial, double and venous occlusions are used to partition pulmonary
      vascular resistance into four segments. In this study, we tested whether the same
      can be accomplished from one double occlusion. In an isolated canine lung left
      lower lobe perfused with blood (flow rate = 500 mL.min-1), the pulmonary arterial
      and venous pressures (Pa and Pv, respectively) were measured directly. Arterial,
      double, and venous occlusions were performed and analysed as usual (Method 1) to
      measure pressures in small arteries and small veins (Pa' and Pv', respectively)
      and capillary pressure (Pc). Alternatively, one double occlusion was analysed
      (Method 2), not only for Pa, Pv and Pc, but also as independent arterial and
      venous occlusions to measure Pa' and Pv'. Method 1 yielded Pa, Pa', Pc, Pv', and
      Pv (Baseline) of 14.2 +/- 1.7, 10.8 +/- 1.6, 8.9 +/- 1.9, 7.3 +/- 1.5 and 1.3 +/-
      0.6 mmHg, respectively (1 mmHg = 0.133 kPa). Method 2 yielded values for the same
      five pressures equal to 14.7 +/- 2.1, 11.0 +/- 2.2, 8.9 +/- 1.9, 7.3 +/- 1.3 and
      1.3 +/- 0.6 mmHg, respectively. There was no significant difference in the
      pressure profile obtained using the two methods, nor were there differences
      during hypoxia and angiotensin infusion. These results suggest that a more
      thorough analysis of the double occlusion can provide the same information about
      distribution of vascular resistance as provided by a combination of the three
      occlusions. The advantage of the new approach is that fewer occlusions are needed
      and resistance distribution can be assessed during a transient response. Because
      all pressures are derived from one occlusion, the pressures would be more
      accurate relative to each other.

PMID- 8980974
TI  - Low intensity peripheral muscle conditioning improves exercise tolerance and
      breathlessness in COPD.
AB  - This randomized, controlled study investigated the physiological effects of a
      specially designed 12 week programme of isolated conditioning of peripheral
      skeletal muscle groups. The programme required minimal infrastructure in order to
      allow continued rehabilitation at home after familiarization within hospital.
      Forty eight patients, aged 40-72 yrs with chronic obstructive pulmonary disease
      (COPD) (mean (SD) forced expiratory volume in one second (FEV1) 61 (27)% of
      predicted normal) were randomly allocated into training (n = 32) and control (n =
      16) groups. Physiological assessments were performed before and after the 12 week
      study period, and included peripheral muscle endurance and strength, whole body
      endurance, maximal exercise capacity (maximum oxygen consumption (V'O2,max)) and
      lung function. The training group showed significant improvement in a variety of
      measures of upper and lower peripheral muscle performance, with no additional
      breathlessness. Whole body endurance measured by free arm treadmill walking
      increased by 6,372 (3,932-8,812) 3 (p < 0.001). Symptom-limited maximal V'O2 was
      unchanged. However, the training group showed a reduction in ventilatory
      equivalents for oxygen and carbon dioxide, both at peak exercise and at
      equivalent work rate (Wmax). In summary, low intensity isolated peripheral muscle
      conditioning is well-tolerated, simple and easy to perform at home. The various
      physiological benefits should enable patients across the range of severity of
      chronic obstructive pulmonary disease to improve daily functioning.

PMID- 8980973
TI  - Oxygen saturation during daily activities in chronic obstructive pulmonary
      disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) frequently develop
      nocturnal oxygen desturation because of alveolar hypoventilation, worsening of
      ventilation-perfusion mismatch, and sometimes obstructive sleep apnoeas. In
      contrast, little is known about their oxygen status during the various activities
      of daily life. The aim of this study was to compare the oxygen saturation profile
      during day and night, and to assess the influence of different daily activities
      in COPD. During a rehabilitation programme, we studied 30 patients with moderate
      to-severe COPD (median forced expiratory volume in one second (FEV1) 37% of
      predicted), without marked hypoxaemia (median arterial oxygen tension (Pa,O2) 9.1
      kPa). Arterial oxygen saturation (Sa,O2) was assessed by pulse oximetry during
      night (8 h) and day (10.5 h). The mean and minimal Sa,O2 were calculated, and
      desaturations were defined as Sa,O2 falls > 4%.h-1. Daily activities were
      identified by the patients as resting, eating, washing, nebulization therapy and
      walking. Mean Sa,O2 was lower during the night (88%) than during the day (89%).
      In contrast, minimal Sa,O2 was lower during the day (69%) than during the night
      (72%), and the number of desaturations was higher during the day (8.6
      desaturations.h-1) than during the night (6.8 desaturations.h-1). Mean Sa,O2 was
      88% during walking, which was lower than during resting (90%), nebulization
      (90%), and meals (89%). The number of desaturations was higher during walking
      (13.1 desaturations.h-1), washing (12.6 desaturations.h-1), and eating (9.2
      desaturations.h-1) than during resting (5.3 desaturations.h-1). We conclude that
      daily activities, such as walking, washing and eating, are associated with
      transient oxygen desaturation in patients with moderate-to-severe chronic
      obstructive pulmonary disease, even without marked resting hypoxaemia.

PMID- 8980975
TI  - Diagnostic accuracy of a portable recording device (MESAM IV) in suspected
      obstructive sleep apnoea.
AB  - This study evaluated the accuracy of a portable recording device (MESAM IV) in
      identifying obstructive sleep apnoea (OSA). The MESAM IV system measures arterial
      oxygen saturation (Sa,O2), heart rate, snoring sounds and body position, and
      allows both automatic and manual scoring of the recordings. Nocturnal
      polysomnography and MESAM IV recordings were performed simultaneously in 150
      patients with suspected OSA, and were analysed blindly by a different observer.
      Patients with an apnoea-hypopnoea index (AHI) greater than or equal to 10 were
      diagnosed as having OSA. In the evaluation of the discriminatory ability of MESAM
      IV scores, the cut-off point was set to minimize first the exclusion of truly
      diseased patients (i.e. false-negative interpretations), and then confirmation of
      nondiseased subjects (i.e. false-positives). When used as an exclusion test, the
      portable device reached a sensitivity of 0.98 and a specificity of 0.78; as a
      confirmation test, these values were 0.69 and 0.97, respectively. These results
      were achieved with manual scoring, which was superior to automatic scoring.
      Manual scoring was also better than automatic scoring when OSA was defined
      according to other threshold values (> or = 5, 15 and 20) for the AHI. The
      combination of MESAM IV manual scores could reduce the need for diagnostic
      polysomnography in three quarters of the patients clinically suspected of having
      obstructive sleep apnoea, substantially reducing costs associated with diagnostic
      procedures.

PMID- 8980976
TI  - Risk of traffic accidents in patients with sleep-disordered breathing: reduction
      with nasal CPAP.
AB  - Sleepiness whilst driving constitutes a road safety risk. Sleep-related breathing
      disorders are the most frequent medical cause of daytime sleepiness, and
      untreated patients with this condition have been shown to be at a higher risk of
      having accidents while driving. This study addressed the question of the extent
      to which treatment of sleep-disordered breathing by nasal continuous positive
      airway pressure (nCPAP) is related to changes in patient's accident risk. Seventy
      eight male patients requiring treatment of sleep-related breathing disorders with
      nCPAP were enrolled in the study. The protocol included a questionnaire dealing
      with alertness-related problems while driving, an 80 min vigilance test, and the
      Multiple Sleep Latency Test. These baseline evaluations were repeated after 1
      year of treatment with nCPAP. Fifty nine patients completed the study. The
      accident rate was significantly decreased from 0.8 per 100,000 km (untreated) to
      0.15 per 100,000 km with nCPAP treatment. Variables that were considered to be
      likely to increase accident risk (sleeping spells, fatigue, vigilance test
      reaction time, daytime sleep latency) also improved with treatment. We conclude
      that treatment of sleep-disordered breathing by nasal continuous positive airway
      pressure is related to reduction in patient motor vehicle accident rates,
      probably due to the reversal of excessive daytime sleepiness.

PMID- 8980977
TI  - Bacterial colonization as a potential source of nosocomial respiratory infections
      in two types of spirometer.
AB  - The potential risk of spirometers in the transmission of respiratory infections
      has not been yet established. We performed a prospective cross-sectional study to
      determine the rate of colonization of a water-sealed spirometer and a
      pneumotachograph, and the potential risk of cross-transmission of microorganisms
      to patients using each of these devices. Fifty four patients (aged 51 +/- 18
      (mean +/- SD) yrs) were included in the study. All of them had undergone forced
      spirometry with bronchodilator response by means of the water-sealed spirometer
      (n = 36) or the pneumotachograph (n = 18). None had a clinically apparent
      respiratory infection at the time of the study. Routine hygiene measures for
      respiratory equipment were performed before the study protocol. Samples for
      microbiological cultures of different parts both of the water-sealed spirometer
      (proximal and distal tubing, bell and water-bell) and pneumotachograph (proximal
      and distal tubing) were taken daily before and after the usual series of lung
      function tests during a 5 day period. Pharyngeal swab cultures were obtained
      before spirometry and 7 days later in each subject. Thirty six out of a total of
      40 (90%) culture samples from the water-sealed spirometer showed microbial growth
      compared to 4 out of 30 (13%) samples obtained from the pneumotachograph (p <
      0.0001). Significant colonization of the water-sealed spirometer was apparent
      after the third day of the study. The microorganisms most frequently isolated
      were penicillium sp. (62%), Pseudomonas fluorescens (32%), and Burkholderia
      cepacea (48%). Distal tubing, water and water-bell were the parts of the water
      sealed spirometer that showed higher colonization counts (> or = 10(4) colony
      forming units (cfu).mL-1). No transmission sequence of potentially pathogenic
      microorganisms from equipment to patients or vice versa could be demonstrated. In
      summary, the water-sealed spirometer frequently became colonized by
      microorganisms. The potential hazard of such equipment as reservoirs of
      microorganisms suggests a need for the implementation of new hygiene measures for
      their maintenance.

PMID- 8980978
TI  - Home dampness, moulds and their influence on respiratory infections and symptoms
      in adults in Finland.
AB  - The aim of this study was to analyse the prevalence of mouldy homes and their
      association with respiratory symptoms and diseases in a subarctic climate. A
      questionnaire was mailed to a random sample of 2,000 males and females, aged 25
      64 yrs, living in the county of Kuopio, Finland. A total of 1,521 (76%) responded
      and 1,460 were selected for the final analysis. The prevalence of homes with
      visible mould was 4%; with the odour of mould 5%; with damp spots, visible mould
      or the odour of mould 15%; and with moisture/ water damage, damp spots, visible
      mould or the odour of mould 23%. The number of reports of bronchitis, common
      cold, atopy, allergic rhinitis, rhinitis, fever and chills, hoarseness, fatigue,
      difficulties in concentration, lumbar backache and stomach ache were strongly
      associated with living in a damp home. Bronchitis, hoarseness and difficulties in
      concentration had the strongest associations, with adjusted odds ratios (95%
      confidence limits) of: 2.04 (1.49-2.78), 2.23 (1.37-3.63) and 2.17 (1.35-3.50),
      respectively. After controlling for a possible reporting bias by excluding those
      subjects reporting lumbar backache and recurrent stomach pain, eye irritation and
      tiredness remained significant. In conclusion, living in a home with mould
      problems may increase the risk of respiratory infections and symptoms in adults.

PMID- 8980979
TI  - Breastfeeding, maternal smoking and lower respiratory tract infections.
AB  - The objective of the study was to assess the relationship between breastfeeding
      and lower respiratory tract infections (LRTIs) during the first year of life,
      with special reference to maternal smoking. A cohort of 3,754 children born in
      1992-1993 in the City of Oslo, Norway was recruited and data were collected at
      birth, 6 and 12 months of age. Complete information was obtained from 3,238
      children (follow-up rate 86%). The main outcome was an episode of a LRTI, such as
      pneumonia, bronchitis or bronchiolitis, based on a self-administered
      questionnaire addressed to parents when the child was 6 and 12 months old. The
      outcome was specified as physician-diagnosed. In logistic regression analysis
      adjusting for confounding, maternal smoking increased the risk of LRTIs in
      children breastfed for 0-6 months (odds ratio (AOR) 1.7; 95% confidence interval
      (95% CI) 1.2-2.4), but not essentially when the child was breastfed for more than
      6 months (AOR 1.1; 95% CI 0.7-1.6). Short-term breastfeeding (0-6 months) and no
      maternal smoking was related to an adjusted AOR of LRTIs of 1.3 (95% CI 1.0-1.7),
      and short-term breastfeeding combined with maternal smoking was related to an
      adjusted AOR of 2.2 (95% CI 1.6-3.1), as compared with long-term breastfeeding
      and no maternal smoking. The present study indicates a protective effect of long
      term breastfeeding on the risk of lower respiratory tract infection during the
      first year of life. The results suggest that the protective effect is strongest
      in children exposed to environmental tobacco smoke.

PMID- 8980980
TI  - Seasonal variation in community-acquired pneumonia.
AB  - Seasonal variation in the incidence of disease in general, and of infectious
      diseases in particular, is vitally important information for epidemiologists and
      for clinicians who deal with these diseases. In relation to community-acquired
      pneumonia (CAP), the seasonal distribution of the disease and, in particular, of
      each of the specific aetiological agents is important. All 346 adult patients who
      were admitted to a regional hospital in southern Israel for CAP over a period of
      1 year were included in a prospective study. As part of the study, a
      comprehensive diagnostic work-up was performed to identify the specific causative
      agents for CAP. The study findings were analysed and are presented in terms of
      the seasonal distribution of the disease. Thirty four percent of CAP cases
      occurred in the spring and only 18% in the autumn (p = 0.036). Respiratory
      viruses CAP were predominant in the winter and spring (p = 0.009), whilst
      Mycoplasma pneumoniae CAP reached its peak incidence of 41% in the spring
      compared with 15% during the winter months (p = 0.054). No significant seasonal
      predominance was observed for the other specific aetiological agents of CAP. In
      58% of the CAP patients who were hospitalized in the autumn we identified a
      pneumococcal aetiology, whilst this agent was found in only 32% of the cases in
      the winter. In contrast with popular public opinion, winter with its low
      temperatures is not the main reason for the development of community-acquired
      pneumonia. Most of the specific aetiologies for community-acquired pneumonia,
      with the exception of respiratory viruses and Mycoplasma pneumoniae, have no
      seasonal predilection.

PMID- 8980981
TI  - Interferon-gamma in 388 immunocompromised and immunocompetent patients for
      diagnosing pleural tuberculosis.
AB  - The level of interferon-gamma (IFN-gamma) in pleural fluid has been reported to
      be increased in pleural tuberculosis. Nevertheless, its diagnostic value has not
      yet been well-established, and immunocompromised patients have not previously
      been evaluated. The aim of this study was to determine the value of the IFN-gamma
      level in pleural fluid for diagnosing tuberculous pleurisy in immunocompetent and
      immunocompromised patients. Three hundred and eighty eight consecutive patients
      were studied prospectively (73 with tuberculous pleural effusions, including nine
      with concurrent human immunodeficiency virus (HIV) infection and one after liver
      transplantation, and 315 with nontuberculous effusions). IFN-gamma was measured
      by radioimmunoassay. The sensitivity of the test, using a 3.7 U.mL-1 cut-off
      point, was 0.99 (95% confidence interval (95% CI) 0.93-1.00) and the specificity
      was 0.98 (95% CI 0.96-1.00). The sensitivity of the test did not differ in HIV
      positive and HIV-negative patients. Patients with lymphoma, vasculitis or
      vascular connective tissue disease did not have abnormal IFN-gamma values. In
      conclusion, the level of interferon-gamma in pleural fluid is a very good
      diagnostic marker of tuberculous pleural effusion, even in immunocompromised
      patients.

PMID- 8980982
TI  - Pulmonary hyperinflation a clinical overview.
AB  - Pulmonary hyperinflation is usually defined as an abnormal increase in functional
      residual capacity, i.e. lung volume at the end of tidal expiration. As such, it
      is virtually universal in patients with symptomatic diffuse airway obstruction.
      Hyperinflation inferred from a standard chest radiograph implies an increase in
      total lung capacity. The relaxation volume of the respiratory system (Vr)
      increases in patients with chronic airway disease as a result of changes in the
      elastic properties of the lungs and chest wall. In addition, a variable degree of
      dynamic hyperinflation may be present. This results from the onset of inspiration
      before lung volume has fallen to Vr. Dynamic hyperinflation is frequently present
      at rest in patients with moderate-to-severe airway obstruction, and it increases
      further on exercise, thereby increasing the mechanical load on the inspiratory
      muscles and at the same time reducing their mechanical advantage. Important
      clinical consequences and associations of hyperinflation include: distortions of
      chest wall motion; impaired inspiratory muscle function; increased oxygen cost of
      breathing; greater likelihood of hypercapnia; impaired exercise performance; and
      greater severity of breathlessness. The symptomatic improvement after treatment
      with a bronchodilator may be due, in part, to lessening of hyperinflation.

PMID- 8980983
TI  - The role of the host defence response in the progression and outcome of ARDS:
      pathophysiological correlations and response to glucocorticoid treatment.
AB  - The host defence response (HDR) to insults is similar regardless of the tissue
      involved and consists of an interactive network of simultaneously activated
      pathways that act in synergy to increase the host's chance of survival. Among
      this cascade of integrated pathways, three aspects of the HDR, inflammation,
      coagulation and tissue repair, are analysed separately to explain the
      histological and physiological changes occurring at the tissue level in
      unresolving acute respiratory distress syndrome (ARDS). Cellular responses in HDR
      are regulated by a complex interaction among cytokines, and cytokines have
      concentration-dependent biological effects. The degree of initial HDR may
      determine the progression of ARDS. On Day 1 of mechanical ventilation and over
      time, nonsurvivors of ARDS have significantly higher plasma and bronchoalveolar
      lavage inflammatory cytokine levels than survivors. In the absence of inhibitory
      signals, the continued production of HDR mediators prevents effective restoration
      of lung anatomy and function by sustaining inflammation with tissue injury, intra
      and extravascular coagulation and proliferation of mesenchymal cells
      (fibroproliferation) with deposition of extracellular matrix resulting in
      fibrosis. Glucocorticoids inhibit the HDR cascade at virtually all levels; their
      gradual and generalized suppressive influence protects the host from
      overshooting. In patients with exaggerated HDR, however, cytokine elevation may
      cause a concentration-dependent resistance to glucocorticoids by reducing
      glucocorticoid receptor binding affinity. Recent clinical and experimental
      studies have shown that effective containment of the HDR in unresolving ARDS may
      be achieved only if glucocorticoid administration is prolonged. A double-blind
      randomized study is in progress to evaluate the role of prolonged glucocorticoid
      treatment in unresolving ARDS.

PMID- 8980984
TI  - Nitric oxide in exhaled air.
AB  - Much interest is now being focused on measurements of nitric oxide (NO) in
      exhaled air. In healthy subjects exhaled NO seems to originate mainly in the
      nasal airways, whereas the contribution from the lower respiratory tract is low.
      In certain inflammatory airway disorders, the excretion of NO into the airways is
      altered resulting in changes in the levels of NO in exhaled air. New techniques
      have been developed to measure NO release at different levels of the airways:
      asthmatics show increased orally-exhaled NO levels, whereas patients with cystic
      fibrosis or Kartagener's syndrome exhibit a marked reduction in nasal release of
      NO. It has been suggested that measurements of exhaled NO may be clinically
      useful in noninvasive diagnosis and monitoring of inflammatory airway diseases.
      To further evaluate the potential clinical usefulness of measurement of exhaled
      NO, it is vital to explore how airway NO production is normally regulated and
      what factors influence airway NO excretion.

PMID- 8980985
TI  - Evaluation of the THRESHOLD trainer for inspiratory muscle endurance training:
      comparison with the weighted plunger method.
AB  - Inspiratory muscle training (IMT) has been shown to enhance exercise performance.
      The weighted plunger (WP) system of inspiratory threshold loading is the most
      commonly used method of IMT, but is expensive and cumbersome. We have evaluated a
      commercially available portable spring-loaded IMT device, the THRESHOLD trainer.
      The WP and THRESHOLD trainer devices were evaluated with their opening pressures
      set, in random order, at 10, 20, 30 and 40 cmH2O. Using an airpump, pressure at
      the valve inlet was recorded at the point at which the valve opened, and at
      airflow rates of 20, 40, 60, 80 and 100 L.min-1. Ten THRESHOLD trainers were then
      compared using the same opening pressures and airflow rates. Finally, 10 patients
      with stable chronic heart failure (CHF) inspired, in random order, through the WP
      and THRESHOLD trainer for 4 min each. The pressure-time product (PTP) was
      calculated for each 4 min period, to compare the work performed on inspiring
      through each device. The mean measured opening pressures for the WP set at 10,
      20, 30 and 40 cmH2O, were 9.0, 19.3, 27.9 and 39.2 cmH2O, respectively, and there
      was little change over the range of flow tested. Corresponding values for the
      THRESHOLD trainer were 7.5, 16.9, 26.2 and 39.1 cmH2O, with the pressure being
      closer to the set pressure as flow increased to that seen in clinical practice.
      The 10 different trainers tested performed very similarly to one another. Work
      performed (as measured by PTP) on inspiring through the WP and THRESHOLD trainer
      was not significantly different. Although less accurate than the weighted
      plunger, the THRESHOLD trainer is an inexpensive device of consistent quality. In
      a clinical setting it would be a satisfactory option for inspiratory muscle
      training in most patients, but less so in patients with very low inspiratory flow
      rates.

PMID- 8980986
TI  - Adult respiratory distress syndrome and pancytopenia associated with miliary
      tuberculosis in a HIV-infected patient.
AB  - Adult respiratory distress syndrome (ARDS) is a rare but severe complication of
      miliary tuberculosis, which may appear even after introduction of
      antituberculosis therapy. Mortality has been reported to be as high as 100% if
      there is associated pancytopenia. We report a case of a patient infected with the
      human immunodeficiency virus who presented with miliary tuberculosis associated
      with pancytopenia and adult respiratory distress syndrome.

PMID- 8980987
TI  - Connective tissue disease due to intentional inhalation of scouring powder.
AB  - There have been reports in the literature of acute and chronic silicosis and
      connective tissue disease induced by occupational exposure to silica in factories
      producing scouring powder. Reports of connective tissue diseases induced by
      intentional inhalation of such a powder are rare and perhaps underestimated. We
      report the case of a young woman who developed Sharp's syndrome 5 yrs after
      diagnosis of acute silicosis due to scouring powder inhalation. The frequency of
      diseases from scouring powder as well as physiopathological and therapeutical
      issues of the association of pneumoconiosis and connective tissue disease are
      discussed.

PMID- 8980989
TI  - Radiation pneumonitis complicating mediastinal radiotherapy postpneumonectomy.
AB  - Radiation pneumonitis is a well-characterized clinicopathological syndrome. The
      severity of radiation-induced lung injury correlates, among other factors, with
      the extent of lung volume incorporated within the field of radiation. The present
      article describes the cases of two patients with radiation pneumonitis following
      pneumonectomy and mediastinal radiotherapy. Postpneumonectomy pulmonary
      mediastinal shift of the remaining lung towards the operated side, with inclusion
      of lung parenchyma within the "mediastinal" radiation portals, resulted in a
      substantial (albeit clinically unsuspected) radiation pneumonitis. Chest computed
      tomography in the postpneumonectomy patient may be helpful to evaluate the degree
      of pulmonary-mediastinal shift and optimization of the radiotherapy field.

PMID- 8980988
TI  - Pneumonitis during interferon and/or herbal drug therapy in patients with chronic
      active hepatitis.
AB  - We report four cases of acute pneumonitis due either to interferon, or a herbal
      drug, "Sho-saiko-to", or both in combination, in patients with chronic active
      hepatitis, focusing on its pathogenesis and response to prednisolone therapy.
      These cases shared common clinical features: fever, dry cough, dyspnoea,
      hypoxaemia, diffuse infiltrates both on chest radiography and chest computed
      tomography, restrictive pulmonary functional impairment, and alveolitis on
      examination of transbronchial lung biopsy, all of which suggest acute
      interstitial pneumonia. Furthermore, lymphocytosis was observed in association
      with the dominant CD8+ T-cell subset in bronchoalveolar lavage fluid. A
      lymphocyte stimulation test using peripheral blood was positive to interferon in
      one case and to Sho-saiko-to in another. All patients responded to oral
      prednisolone therapy. Peripheral soluble interleukin-2 receptor levels decreased
      in parallel with improvement in the clinical course. All patients were free of
      symptoms with a follow-up of 1-3 yrs. We conclude that interferon- and/or Sho
      saiko-to-induced acute pneumonitis may be due to allergic-immunological
      mechanisms rather than toxicity, and that peripheral levels of soluble
      interleukin-2 receptor appear to be good markers of disease activity.

PMID- 8980990
TI  - Variability of markers of airway inflammation in BAL.

PMID- 8980991
TI  - Molecular pathogenesis of thyroid cancer: the significance of oncogenes, tumor
      suppressor genes, and genomic instability.

PMID- 8980992
TI  - Redifferentiation therapy of differentiated thyroid carcinoma with retinoic acid:
      basics and first clinical results.
AB  - Retinoic acids (RA) regulate growth and differentiation of normal epithelial
      tissue. They have been employed in anticancer treatment and showed positive
      effects in hematopoetic and various epithelial tumors. Experimental data with
      follicular thyroid tumor cells showed strong evidence of induction of
      differentiated cell function and antiproliferative effects. Based on these data a
      consecutive series of 10 patients with advanced thyroid carcinoma were treated
      with 13-cis-retinoic acid (Roaccutan) 1.5 mg/kg body weight for six weeks. Follow
      up demonstrated renewed uptake of radioiodine in 4 of 10 patients allowing
      performance of further radioiodine therapy. Reduction in tumor size due to
      antiproliferative effects of RA could not yet be verified.

PMID- 8980993
TI  - Effects of retinoids and role of retinoic acid receptors in human thyroid
      carcinomas and cell lines derived therefrom.
AB  - Retinoic acids (RAs), well characterized regulators of proliferation and
      differentiation, partly re-differentiate follicular thyroid carcinoma cell lines
      (FTC-133, FTC-238, and HTC-TSHr) as well as SV40-transfected immortalized thyroid
      cell lines (ori3 and 7751). This is indicated by the stimulation of type I 5'
      deiodinase and other differentiation markers. As demonstrated by RT-PCR,
      electrophoretic mobility shift, and [3H]-retinoic acid binding assays, thyroid
      carcinoma cell lines express RA receptor mRNAs and functional ligand- and DNA
      binding receptor proteins able to mediate RA-dependent signal transduction.
      Together, these properties make these thyroid-derived cell lines useful in vitro
      models for studying the effects of an RA re-differentiation therapy of thyroid
      cancer.

PMID- 8980994
TI  - Expression of apoptosis-related proteins in thyroid tumors and thyroid carcinoma
      cell lines.
AB  - Whereas in normal human thyroid tissue total cell mass is maintained by a balance
      between cell proliferation and apoptosis, the programmed cell death, in thyroid
      tumors this equilibrium is disrupted. In tumor cells, an augmented proliferation
      rate is no longer counterbalanced by an equally enhanced apoptosis resulting in
      an increased netto growth rate. To investigate regulation of apoptosis in thyroid
      tumors, we analyzed the expression of apoptosis-related proteins of the bcl-2
      family in human thyroid tissues and in the human thyroid carcinoma cell lines FTC
      133, HTC, HTC-TSHr and HTh74. In comparison to normal tissue, we detected an
      increased expression of the anti-apoptotic protein bcl-2 in adenomas, whereas
      follicular carcinomas showed various expression of bcl-2 with decreased levels in
      32% of cases. BclxL expression was comparable in all tissues examined. The pro
      apoptotic protein bax was expressed at lower levels in carcinomas than in
      adenomas, whereas bak and bclx were expressed in the same order of magnitude in
      all tissues examined. In contrast, thyroid carcinoma cell lines exhibited a
      relatively strong expression of bclxL, but a weak expression of bcl-2. In all
      four cell lines, the amounts of the pro-apoptotic proteins bax, bak and bclx were
      higher than in most tumor tissues. Our data show that in thyroid tumors
      expression of members of the bcl-2 protein family is not uniform. Rather, the
      expression pattern of pro- and anti-apoptotic proteins in thyroid tumors is
      heterogeneous. This may, at least in part, reflect the futile attempt of tumor
      cells to counterbalance the action of growth-promoting factors in thyroid tumor
      igenesis.

PMID- 8980995
TI  - Cell adhesion receptors and gap junctions in normal and neoplastic transformed
      thyrocytes.
AB  - In the thyroid cell adhesion receptors and gap junctions establish a complex
      modular network defining the structural properties of cells, their interactions
      with neighboring cells and the extracellular matrix. Neoplastic alterations of
      this network can lead to an imbalance of cell to cell communication and allows
      transformed cells to escape from the tissue to generate metastases. The present
      manuscript summarizes general and thyroid-specific aspects of the molecular basis
      of cell-cell contacts, an expanding field of tumor biology.

PMID- 8980996
TI  - The regulation of proliferation and invasion in differentiated thyroid cancer by
      growth factors.
AB  - Invasion and metastasis are the primary cause of death in patients with
      follicular thyroid cancer (FTC). The thyroid is a micro-economic system in which
      proliferation and differentiation was supposed to be under the major control of
      only a single hormone (thyroid stimulating hormone-TSH). It has shown, however,
      that a complex network of various growth factors regulates growth and invasion of
      thyroid cancer cells. A growing literature has established the close association
      between malignant tumor progression and growth regulatory aberrations in cancer
      cells. Most of these studies have focused on the phenomenon, that advanced and
      more aggressive tumors or metastases lost the sensitivity to growth inhibitors,
      such as transforming growth factor beta. These findings highlight two aberrations
      of growth regulation which may favour progression of malignant disease and
      acquisition of metastatic competence: (1) Resistance to growth factor inhibitors
      and (2) growth autonomy of metastatic follicular thyroid cancer cells.

PMID- 8980997
TI  - Molecular aspects of the pathogenesis of nodular goiters, thyroid nodules and
      adenomas.
AB  - One of the most significant results of recent molecular thyroid research on the
      pathogenesis of nodular goiters may be the finding that not only thyroid adenomas
      but also many thyroid nodules are clonal in origin and thus are true benign
      tumors. Both clonal and polyclonal nodules may coexist within the same nodular
      goiter. Since clonal nodules may secondarily acquire a heterogeneous phenotype,
      they can become morphologically indistinguishable from polyclonal lesions. The
      molecular mechanisms that generate thyroid nodules and adenomas are still poorly
      understood. Certainly, the recent detection of activating mutations in the TSH
      receptor and the Gs alpha gene in a subset of toxic thyroid adenomas and nodules
      may explain the generation of hyperfunction in these tumors, but there is strong
      evidence that these mutations are not the unique and primary cause of tumor
      formation. In this respect the concept of natural occurring heterogeneity of
      thyroid growth and function can provide a plausible explanation for the early
      stages of nodular transformation: If a thyrocyte has a high intrinsic growth
      potential or if it is affected by overexpression of a protooncogene or a growth
      factor or hit by an oncogene or other molecular events, the cell will outgrow and
      form a tumor. The inborn qualities of proliferating cells or the sequence of
      various genetic alterations in proliferating cells will in turn determine the
      phenotype and function of the tumor.

PMID- 8980998
TI  - Role of basic fibroblast growth factor in the pathogenesis of nodular goiter.
AB  - Thyroid epithelial cells are known to produce several growth factors and
      cytokines which influence thyroid cell growth and function in an autocrine and/or
      paracrine manner. It is already known that insulin-like growth factor I (IGF I)
      is overexpressed in toxic adenomas whereas epidermal growth factor (EGF) is found
      predominantly in thyroid neoplasia. We now investigated the expression of bFGF by
      immunohistochemistry in thyroid tissue of patients with toxic adenoma (n = 27),
      cold nodules (n = 27) and for comparison in Graves' disease (n = 5). In addition
      bcl-2-oncoprotein expression in these tissues were also detected by
      immunohistochemistry. Most of bFGF immunostaining was found in the connective
      tissue of all thyroid tissues with a predominance in adenomas and in Graves'
      diseases. The collagen surrounding the thyroid follicles close to their basal
      membrane were homogeneously and intensively stained. All the cytoplasm of
      fibroblast in the connective tissue were strongly positive. Within the cytoplasm
      of only 2-10% thyroid epithelial cells bFGF immunostaining was found without any
      difference between toxic adenomas or cold nodules. In the tissue of patients with
      Graves' disease, less than 2% of thyrocytes were stained. All thyroid epithelial
      cell showed clearly an immunostaining for bcl-2-oncoprotein in nodular goiter as
      well as Graves' disease.

PMID- 8980999
TI  - Enhanced functional activity in thyroid adenomas in vitro.
AB  - The majority of thyroid adenomas have been shown to be of clonal origin. In a
      portion of them, somatic or germline point mutations leading to altered TSH
      receptor or Gs alpha-proteins have been found. The constitutive activation of
      these proteins consecutively stimulate cAMP-levels. Expression of the TSH
      receptor mutants in mammalian cells leads to increased cAMP-production compared
      to cells transfected with the wild type receptor. Presently, the role of these
      mutations in the development and growth of such tumours is still unclear. In our
      own investigations we made an attempt to evaluate the functional significance of
      these observations. In nodular tissue derived from patients with functioning
      autonomous adenoma we found significantly higher basal and TSH stimulated thyroid
      hormone releasing activity than in the surrounding paranodular tissue and in
      thyroid tissue derived from patients with euthyroid goiter. These findings
      indicate a functional relevance of constitutively activated intracellular signal
      transducing cascade in thyroid adenomas that may lead to hyperthyroidism in the
      presence or absence of external thyroid stimulators.

PMID- 8981000
TI  - Iodolactones and iodoaldehydes--mediators of iodine in thyroid autoregulation.
AB  - Within the last decades multiple iodolipid-classes have been identified in
      thyroid tissue. For a long time they have been supposed to be involved in thyroid
      autoregulation, but for the time being no specific compounds could be isolated. A
      new approach was stimulated by the finding that thyroid cells were able to
      iodinate polyunsaturated fatty acids to form iodolactones and by the
      identification of alpha-iodohexadecanal (alpha-IHDA) as the major compound of an
      iodolipid fraction. alpha-IHDA exerts multiple inhibitory effects on adenylate
      cyclase, NADPH-oxidase and thyroid peroxidase. Therefore, it is speculated as a
      mediator of the Wolff-Chaikoff-effekt and to be involved in the autoregulation of
      specific thyroid functions mediated by the cyclic adenosine-3',5'-monophosphate
      (cAMP)-pathway. Meanwhile 6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid delta
      lactone (delta-iodolactone) has been identified in human thyroid tissue and it
      could be demonstrated that this iodoeicosanoid specifically inhibits signal
      transduction pathways induced by local growth factors such as epidermal growth
      factor (EGF) and basic fibroblast growth factor (bFGF). Therefore, delta-iodol
      actones seem to act as mediators of iodine, especially in the autoregulation of
      cAMP-independent thyroid cell proliferation. We will summarize these important
      new findings and discuss the role of these iodolipids on thyroid cell growth
      regulation.

PMID- 8981001
TI  - Prospective study of T cell receptor utilization following the induction of
      murine thyroiditis.
AB  - Murine experimental autoimmune thyroiditis (EAT) is a well established model of
      autoimmune disease initiated by immunization with thyroglobulin. We have
      previously analyzed the T cell receptor (TcR) V gene families used by the
      intrathyroidal lymphocytic infiltrate in CBA/J mice with well established
      thyroiditis EAT and have implicated T cells expressing the mTcR V beta 13 gene
      family. We have now proceeded to examine the time course of mTcR V gene family
      use following immunization with mTg. We used a radiolabelled RT-PCR technique
      with oligonucleotides detecting 17 mouse TcR V beta gene families to examine the
      heterogeneity of the amplified V-D-J (CDR3) fragments. As previously, the TcR V
      beta 13 amplifications showed the expression of two similar homogeneous CDR3
      sizes consistent with two clonally expanded T cell populations. However, such T
      cell clonal expansion was observed to peak at day 25 and by 90 days had markedly
      diminished despite the continuing presence of extensive histologic infiltration.
      An additional immunization with mTg at 63 days failed to maintain the mTcR V beta
      13 clonal presence. Further confirmation of these observations was obtained by
      direct analysis of intrathyroidal T cells rescued from mice with EAT. Such
      intrathyroidal T cells, 25 days after mTg, demonstrated a marked increase in mTcR
      V13 expressing T cells to 9.4% compared to 2% of T cells in peripheral blood. It
      appeared, therefore, that in EAT the accumulation of V13 expressing T cells was a
      transient phenomenon which peaked at 25 days after immunization. The persistence
      of an intrathyroidal infiltration indicated that such T cells must have been
      accompanied by the accumulation and recruitment of additional selected bystander
      T cells. Such non-specific T cells may also have an integral role in the
      progression of autoimmune thyroiditis.

PMID- 8981002
TI  - Epitope mapping of the human TSH receptor; structure function studies.
AB  - With the aid of recombinant DNA technology (PCR/site directed mutagenesis,
      sequencing) the full length coding region of the human TSH receptor was
      manipulated to place a specific epitope peptide tag (FLAG epitope sequence) at
      the carboxyl end of the protein. The resulting construct was cloned into a
      eukaryotic expression vector and stably transfected into HeLa cells. The
      expression/translation of the tagged TSH receptor molecule was monitored by
      immune-precipitation and western blotting of protein lysates, and was found to be
      expressed at considerable levels using the commercially available antibodies
      directed towards the FLAG epitope. This analysis revealed two discrete specific
      bands 90-120 KDa representing, presumably, differently glycosylated forms of the
      receptor. TSH radio receptor assays demonstrated that the FLAG tagged TSH
      receptor bound TSH comparable with the wild type receptor. Furthermore TSH
      stimulated cAMP response in these transfected cells were comparable to the wild
      type receptor, thus demonstrating that the tagged receptor was functionally
      identical to the transfected wild type receptor. These cell lines will be of
      great value when analysing TSH/receptor or receptor/autoantibody interactions
      considering the availability of well characterized experimental anti-TSH receptor
      sera.

PMID- 8981003
TI  - In vitro synthesized TSH receptor as a tool for autoantibody detection.
AB  - Immunoprecipitation is a reliable method for the detection of many antigens but
      so far this has not been applied to the TSH receptor. We demonstrate here a novel
      assay for the detection of antibodies to the TSH receptor using in vitro
      synthesized protein. The TSH receptor was translated in vitro as a stable protein
      of 87 kD (full length) and 50 kD (extracellular), respectively. The 50 kD protein
      reacted by immunoprecipitation analysis with murine and human monoclonal
      antibodies, polyclonal rabbit sera and with a proportion of unfractionated
      Graves' disease sera. A limited form of epitope mapping was achieved with the
      murine monoclonal antibodies. This assay may serve as a new method for the
      detection of autoantibodies to the TSH receptor from patients' sera.

PMID- 8981004
TI  - Effect of Graves' intrathyroidal lymphocytes. Effect of Graves' disease
      intrathyroidal lymphocytes (ITL) on xenotransplants of human thyroid tissue in
      athymic nude mice.
AB  - It has been suggested that ITL are of importance in the pathogenesis of human
      autoimmune thyroid disease. Aim of our study was to investigate function and
      morphology of xenotransplanted human thyroid tissue in nude mice following
      systemic application of lymphocyte preparations from patients with Graves'
      disease (GD) and non-toxic nodular goiter (NTG). ITL obtained from 13 patients
      with GD and peripheral blood lymphocytes (PBL) from 12 patients with NTG were
      injected into nude mice bearing 8 weeks old xenografts of normal human thyroid
      tissue. ITL- and PBL-subsets were analyzed by flow cytometer (FACScan) before
      engraftment. Two days after injection the thyroid transplants were examined
      histologically (HE) as well as immunohistologically by staining with: CD3, CD31,
      CD45R, HLA class II, ICAM-1, VCAM-1, IgG, IgM and Ki67. Flow cytometry showed a
      significant higher number of the lymphocyte-subsets CD3, DR+ and CD4 in GD-ITL as
      compared to the subsets in NTG-ITL. After injection of GD-ITL to the nude mice
      also a significant higher number of CD3+ human lymphocytes was found in the
      transplants. GD-lymphocytes stimulated thyroid tissue function significantly more
      pronounced than NTG-lymphocytes (histomorphological evaluation). In addition, a
      significant increase of HLA-class II, ICAM-1-, VCAM-1-, CD45-expression and
      number of Ig presenting plasma cells were observed only after injection of GD
      ITL. Our data demonstrate, for the first time in vivo (nude mouse model), that GD
      lymphocytes of both peripheral and intrathyroidal origin selectively migrate into
      human thyroid transplants ("homing"). They survive there for at least two days
      and induce significant functional as well as histological changes, like
      expression of gene products and IgG synthesis. These results suggest an important
      role of ITL in the pathogenetic mechanisms and clinical course of GD.

PMID- 8981005
TI  - Expression of cytokines in the thyroid: thyrocytes as potential cytokine
      producers.
AB  - The unstimulated and stimulated thyrocyte is able to produce more different
      cytokines in vitro than any other endocrine cell. Cytokines produced by
      thyrocytes may play a role in the local stimulation and maintenance of immune
      responses against autoantigens in the thyroid, in the modulation of goiter size
      in response to TSH, and in the clinical course of patients with thyroid tumors.
      This paper tries to summarize the results of relevant studies investigating
      cytokine production by thyrocytes. Although there is an agreement in published
      work that thyrocytes secrete a number of cytokines such as II-1, II-6, II-8 and
      TGF-beta in vitro it is unclear whether these factors are produced also by
      thyrocytes in vivo. By the example of GM-CSF in vitro secretion by stimulated
      anaplastic thyroid carcinoma cell lines and stimulated thyrocytes, the relevance
      of these findings during the clinical course of patients with anaplastic thyroid
      tumours is discussed.

PMID- 8981006
TI  - Iodide, cytokines and TSH-receptor expression in Graves' disease.
AB  - The present study was initiated to characterize thyrotropin receptor (TSH-R)
      expression in thyroids from patients with Graves' disease, as well as parameters
      that influence TSH-R expression either causally, such as interferon-gamma (IFN
      gamma), the leading candidate among the cytokines thought to play a key role in
      the initiation of autoimmune thyroid disease, or therapeutically, such as iodide,
      which is used to prepare patients for surgery. Our data show that there is an
      average 4-fold increase of TSH-R mRNA levels in the thyroids of Graves' patients
      coming to surgery, which is paralleled by an increase in TSH-R protein levels and
      TSH binding capacity. The increase does not appear to be related to IFN-gamma
      since IFN-gamma transcripts are barely detectable in most Graves' patients.
      Iodide treatment causes a 2-fold decrease in TSH-R expression in association with
      significant decreases in major histocompatibility complex (MHC) class I and class
      II gene expression. These last data are compatible with a recently enunciated
      "transcription factor hypothesis" according to which abnormally high TSH-R and
      MHC class I and class II gene expression in Graves' thyroids are the result of a
      loss of the normal negative regulation of these genes necessary to allow the
      normal growth and function of the gland, yet preserve self-tolerance.

PMID- 8981007
TI  - Bacterial virulence antigens and the pathogenesis of autoimmune thyroid diseases
      (AITD).
AB  - There is now substantial evidence that autoimmune thyroid diseases (AITD)
      coincide with a subclinical persisting infection with Yersinia enterocolitica
      (YE) which manifests through humoral and cellular immune reactions against YE at
      the onset of AITD. The humoral and cellular crossreactivities of YE with thyroid
      autoantigens are exclusively directed against conformational epitopes of YE
      membrane associated antigens and of YE plasmid encoded virulence proteins (YOPs).
      Especially, the outer membrane domain of the TSH-Receptor (THSR) appears to have
      conformational homologies with YE antigens. Immunological- and molecular
      findings, however, do not allow definite conclusions about a potential role of YE
      infection in AITD, although the evidence is suggestive. Recent investigations on
      the effect of YE-superantigen (Sag) on T-cells from patients with AITD as well as
      AITD like manifestations in YE immunized mice and rats may yield more conclusive
      information about the role of YE infection in the pathogenesis of AITD.

PMID- 8981008
TI  - T cells and orbital connective tissue in endocrine orbitopathy.
AB  - In order to analyse the immunological changes in patients with endocrine
      orbitopathy (EO) the antigenic character of orbital connective tissue was
      studied. Counter-stimulation assays of patients' lymphocytes with autologous
      retrobulbar fibroblasts resulted in a markedly increased lymphocyte proliferation
      in comparison to incubation with retrobulbar control fibroblasts. Proliferation
      tests of retrobulbar T cell lines showed significant responses to autologous
      retro-orbital connective tissue proteins, with molecular weights of 6-10 kD and
      19-26 kD. Phenotypic analysis of orbital T cell lines indicates that they
      consisted predominantly of CD4+ cells. Hyaluronic acid production of orbital
      fibro blasts following co-cultivation with lymphocytes of EO patients or controls
      revealed a threefold increased synthesis in patients with EO. Furthermore,
      distribution pattern of orbital extracellular matrix glycosaminoglycans (GAG)
      differs in EO patients in comparison to controls. The results suggest the
      presence of autoreactive T cells directed against antigens of orbital
      fibroblasts, whose stimulation results in an augmented GAG synthesis in patients
      with EO.

PMID- 8981009
TI  - Molecular analysis of antigen receptor variable region repertoires in T
      lymphocytes infiltrating the intrathyroidal and extrathyroidal manifestations in
      patients with Graves' disease.
AB  - To determine whether T cells infiltrating thyroid, orbital and pretibial tissue
      of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD)
      represent a primary immune response that is directed against certain antigenic
      determinants shared between these involved tissues, we characterized these T
      cells at the molecular level. T cell antigen receptor (TcR) variable (V) region
      gene usage in thyroid, orbital, pretibial tissue and peripheral blood mononuclear
      cells of patients with GD, GO and PTD was assessed using RT-PCR and 22 V alpha
      and 23 V beta gene-specific oligonucleotide primers, followed by Southern
      hybridization analysis using TcR C-region-specific, digoxigenin-labelled
      oligonucleotide probes. In some instances, CDR3- and junctional regions of TcR V
      beta genes were sequenced. Marked restriction and similarities of V alpha and V
      beta gene usage were detected in samples derived from patients with active GO and
      PTD of recent onset. Moreover, sequence analysis of junctional domains of V beta
      families revealed oligoclonality of some intrathyroidal, orbital and pretibial T
      cell populations as well as the presence of conserved junctional motifs shared by
      T cells derived the thyroid gland and the extrathyroidal sites. These data
      suggest that similar antigenic determinants may be responsible for the
      recruitment and oligoclonal expansion of T cells both within the thyroid gland
      and at the involved extrathyroidal sites in Graves' disease.

PMID- 8981010
TI  - Stimulation of thyroidal and extrathyroidal thyrotropin receptors.
AB  - TSH receptor plays a pivotal role in the regulation of thyroid function and is
      intimately involved in the pathogenesis of common thyroid disorders. A lack of
      specificity and absence of down regulation upon stimulation renders the human TSH
      receptor susceptible to exogenous overstimulation, which forms the basis of
      hyperthyroidism in TSHoma, Graves' disease and gestational thyrotoxicosis.
      Further, TSH receptor activation in the absence of exogenous stimulators due to
      the expression of endogenously active mutant receptors has recently been
      described, and may in part account for hyperthyroidism in autonomously
      functioning thyroid nodules. Signal bifurcating by coupling of TSH receptor to
      different G proteins may be a likely mechanism to explain the multitude of
      distinct effects caused by TSH receptor activation including mainly hormone
      production and growth promotion. Also, TSH receptor appears to mediate
      immunological stimulation, its activation by TSH R Ab inducing expression of
      adhesion molecules and HLA class II antigens on thyrocytes. Increasing evidence
      suggests that TSH receptor is not restricted to thyroid and may be expressed in
      extrathyroidal tissues with a potential role in the pathogenesis of Graves'
      orbitopathy.

PMID- 8981011
TI  - Theoretical basis and application of molecular diagnostics.
AB  - Molecular biology has brought much progress in understanding physiology and
      pathophysiology as well as tumor development in thyroidology. The principles of
      gene organisation, regulation, and expression will be mentioned in regard to the
      thyroid and thyroid hormones. A growing number of thyroid disorders are linked to
      molecular events like mutations, deletions, splice errors, gene duplications or
      aberrant expression. The genetic causes and molecular approaches in diagnosis are
      most evident in rare inheritable syndromes, such as familial medullary thyroid
      carcinoma (FMTC, MEN 2), thyroid hormone resistance or non-autoimmune autosomal
      dominant hyperthyroidism. Furthermore, in toxic nodules, papillary and sporadic
      medullary thyroid carcinomas somatic mutations have been found, of which the
      pathogenetic role is still under debate. The molecular tools to diagnose gene
      mutations are mostly based on the polymerase chain reaction (PCR). Screening
      methods include single-strand conformation polymorphism (SSCP), denaturing
      gradient gel electrophoresis (DGGE), and temperature gradient gel electrophoresis
      (TGGE). More specific methods like enzyme restrictions or allele-specific PCR
      require precise knowledge of the mutation which is searched for in genomic DNA.
      DNA sequencing is the safest but not the cheapest or simplest way to detect a
      mutation. Some examples will be given for the application of the above mentioned
      methods in diagnosing certain thyroid diseases.

PMID- 8981012
TI  - Genetic markers in diagnosis and prediction of relapse in Graves' disease.
AB  - Hyperthyroidism of Graves' disease takes an unpredictable clinical course in the
      long-term follow-up. Whereas roughly 30-60% of patients relapse after their first
      antithyroid drug treatment, the likelihood of remission in the remaining group
      can not be foreseen. We have analysed-retrospectively-patients with Graves'
      disease that had been on antithyroid drug treatment for one year and were
      followed up thereafter. Patients were investigated for a variety of clinical
      parameters like ophthalmopathy status and relapse or remission as well as gene
      polymorphisms of the HLA and other regions. Of the 259 patients analysed so far,
      patients with ophthalmopathy did not differ from those without for HLA DQA1 and
      CTLA4 alleles tested. Also, the subgroup of patients with relapses after
      antithyroid drug treatment showed no different distribution of those alleles from
      the group with long-term remission. This study also confirms that the allele HLA
      DQA1* 0501 confers susceptibility to Graves' disease, furthermore, that the CTLA4
      alanine 17 allele is an additional predisposing factor.

PMID- 8981013
TI  - INT-2 gene amplification in differentiated human thyroid cancer.
AB  - Oncogene amplification is frequent in many epithelial tumors and often associated
      with advanced tumor progression. In different epithelial neoplasias it helps to
      provide prognostic information on individual patients. The present study was
      performed to evaluate the hitherto unknown prevalence of INT-2 gene amplification
      and its potential usefulness as prognostic marker in patients with human thyroid
      cancer. We used differential quantitative polymerase chain reaction and
      fluorescent DNA technique as a reliable method to detect low copy-number
      amplification of oncogenes from archival carcinoma specimens. Sequences from the
      int-2 gene and the single copy gamma-interferon gene were amplified
      simultaneously by PCR and quantified on a fluorescence activated sequencer.
      Native tumor tissue from 63 patients with differentiated thyroid cancer (43
      papillary, 3 oncocytary, and 17 follicular) and from 12 goiters was analyzed by
      differential quantitative polymerase chain reaction. The study group contained
      many far advanced tumors. 40% of tumors were recurrent, 35% were staged T4 tumors
      and 70% presented with lymph node metastases. The prevalence of INT-2
      amplification was 12% for follicular and 7% for papillary carcinomas. In goiter
      tissue no amplification was found. Amplification was only 2-4fold in positive
      cases. Low grade amplification is of no apparent importance in differentiated
      thyroid cancer.

PMID- 8981014
TI  - Molecular genetics of primary and secondary hyperparathyroidism.
AB  - Hyperparathyroidism (HPT) can be caused by solitary parathyroid adenomas and
      carcinomas, and primary and secondary multiglandular parathyroid disease. Primary
      HPT is also a feature of several hereditary diseases e.g. multiple endocrine
      neoplasia type 1 and type 2A (MEN1 and 2A), familial hypocalciuric
      hyperparathyroidism (FHH), the HPT-jaw tumor syndrome (HPT-JT), and familial
      isolated HPT. Summarizing data from the literature and our own observations,
      various genetic abnormalities are observed in the pathogenesis of HPT. These
      include chromosomal deletions of the MEN1 locus on 11q in sporadic and MEN1
      associated primary HPT, of RB1 on 13q in carcinomas, and of the FHH gene located
      on 3q in sporadic primary and secondary HPT. Genetic material is also lost from
      chromosomes 1p, 6q, 15q and X suggesting loss of yet unidentified tumor
      suppressor genes in these regions. In addition the HRPT2 gene on 1q, as well as
      the proto-oncogenes RET on 10q and PRAD1 on 11q are associated with a subset of
      parathyroid tumors.

PMID- 8981015
TI  - Application of genetic screening in families with hereditary medullary thyroid
      carcinoma.
AB  - In 34 families out of 35 with hereditary medullary thyroid cancer a mutation in
      the RET proto-ongene could be identified. In 84 family members gene carrier state
      could be proven, in 75 family members gene carrier state could be excluded. The
      majority of gene carriers (67 out of 84) were symptomatic while 17 gene carriers
      were diagnosed in a presymptomatic state. 9 of the 17 presymptomatic gene
      carriers had prophylactic thyroidectomy. On histological examination C-cell
      hyperplasia or multifocal microcarcinomas could be proven. In one of our families
      with familial MTC no germline mutation in the RET gene could be detected. In this
      family pentagastrintests and indirect genotyping are necessary. Four family
      members of MEN 2A families have had thyroidectomy on the basis of pentagastrin
      testing and now proved not to be gene carriers. The application of genetic
      testing in families with hereditary thyroid carcinoma has further improved
      management in these families - it is the first step in the evaluation of family
      members at risk.

PMID- 8981016
TI  - Periodically hyperthyroid phenotype in thyroid hormone resistance is associated
      with mutation D322N in the thyroid hormone receptor beta gene: transcriptional
      properties of the mutant and the role of retinoid X receptor.
AB  - We report a point mutation in the ligand-binding domain of the TR beta 1 gene in
      an affected patient and his daughter. The phenotype was borderline hyperthyroid
      with periodic aggravation of symptoms. In the cognate variant TR beta (TR beta
      CN) amino acid codon 322 was exchanged from aspartic acid to asparagine. TR beta
      CN revealed strongly decreased T3-binding activity. At low T3 levels TR beta-CN
      transactivated a palindromic thyroid hormone response element (TRE-PAL) only to a
      limited extend, whereas full activity was retained at a high T3 concentration. At
      low T3 levels, TR beta-CN exerted a dominant negative effect on wild-type TR
      beta, whereas this effect was diminished in the presence of high T3
      concentrations. TR beta-CN could not be activated by retinoid X receptor (RXR)
      beta in the presence of T3, whereas addition of 9cis-retinoic acid (9c-RA)
      resulted in the transactivation of TRE-PAL through RXR beta independently of the
      presence of TR beta-CN. In conclusion, the time dependent variable THR phenotype
      of patient CN might be influenced by the differential expression of RXRs and the
      T3 and 9c-RA hormonal status.

PMID- 8981017
TI  - The gene for the thyrotropin receptor (TSHR) as a candidate gene for congenital
      hypothyroidism with thyroid dysgenesis.
AB  - According to the central role of the TSH receptor for thyroid function and growth
      the gene for the TSH receptor is a possible candidate gene for mutations which
      result in an impairment of thyroid growth and function (Vassart and Dumont 1992).
      First evidence for the role of TSH receptor defects in the pathogenesis of
      congenital thyroid disorders was elucidated by the presence of activating
      germline mutations leading to congenital hyperthyroidism (Duprez et al., 1994).
      After the finding of partial loss-of-function mutations leading to
      hyperthyrotropinemia (Sunthornthepvarakul et al., 1995) it was speculated that a
      more severe phenotype with hypothyroidism and hypoplasia of the gland (thyroid
      dysgenesis) would be the result, if complete loss-of-function mutations like the
      isoleucine167 to asparagine mutation would occur in a homozygote or compound
      heterozygote state. The screening of TSHR gene mutations by SSCP in a well
      defined cohort of 100 children with congenital hypothyroidism (CH), diagnosed and
      followed since 1978 in the Childrens Hospital of Berlin, revealed one patient
      with hypoplasia of the thyroid to be positive for two compound heterozygote
      inactivating mutations of the TSHR gene, indicating thereby that the clinical
      approach to define phenotypes of interest could be helpful to understand the
      fundamental process of thyroid development.

PMID- 8981018
TI  - Screening for mutations of the human thyroid peroxidase gene in patients with
      congenital hypothyroidism.
AB  - While congenital hypothyroidism in 80-90% of the affected individuals is caused
      by thyroid dysgenesis (athyrosis, ectopy or hypoplasia), hypothyroidism in
      patients with a thyroid gland of normal position and size can be due to
      regulatory or enzymatic defects of thyroid hormone biosynthesis. Beside defects
      of thyroglobulinsynthesis, defects of the sodium-iodide-transporter or the TSH
      receptor, a defect of the thyroidperoxidase, the key-enzyme of thyroid hormone
      biosynthesis, can cause a total iodide organification defect and thereby
      congenital hypothyroidism. We screened 14 of 103 patients (13.6%) with non
      familial congenital hypothyroidism and a normally developed thyroid gland
      detected by the newborn screening program with the PCR-SSCP (single-stranded
      conformational-polymorphism) technique for mutations in the exons 2, 8, 9, 10 and
      14 of the human thyroperoxidase gene, and in which mutations had been described
      previously in Dutch and Brazilian families with total organification defects.
      Most of the previously reported mutations were found in exons 8, 9 and 10 which
      code for the caralytic part of the enzyme. In two patients a GGCC-duplication in
      exon 8 was detected leading to a premature stop codon in exon 9. While one
      patient without neonatal goiter was homozygous for this mutation, the second
      patient was only heterozygous thus demanding another mutation on the second TPO
      allel to explain the phenotype. Since the GGCC duplication is easily demonstrable
      by a NaeI digestion, because it creates a restriction site for this enzyme,
      screening for this mutation is indicated since it is easy to perform. In contrast
      to the perchlorate discharge test molecular genetic studies are less invasive,
      but as useful in making a definitive diagnosis in the individual patient.
      Furthermore it is the first feasible step to study the etiology and epidemiology
      of the so far only putative defects of thyroid hormone biosynthesis leading to
      congenital hypothyroidism.

PMID- 8981019
TI  - Mutations of the TSH receptor as cause of congenital hyperthyroidism.
AB  - 4 patients of two families with congenital persistent hyperthyroidism without
      detectable autoantibodies are reported. The members of the first family affected
      by hyperthyroidism, i.e. the mother and her two children, showed a germline
      mutation, a transition of GCC to GTC in the genomic DNA of the TSH receptor,
      leading to an exchange of alanine by valine at the position 623. The mother was
      thyroidectomized at two times because of recurrent nodular goiter. The third
      child of a healthy second family showed a transition of AGC to AAC leading to an
      exchange of serine by asparagine at the position 505 of the TSH receptor. The
      mutation of family 1, as a somatic point mutation leading to autonomous thyroid
      adenoma, has originally been demonstrated to constitutively activate TSH
      independent cAMP accumulation. The functional tests of the TSH receptor gen
      mutation, detected in family 2, are ongoing, but an exchange of serine by
      arginine at the same position has been shown to lead to constitutively active
      cAMP accumulation. The cases of congenital hyperthyroidism in the first family
      lead to a reduction of the birth weight and head circumference and to a neonatal
      but not fetal tachycardia. Bone age of both children was accelerated by one year.
      In contrast to that, congenital hyperthyroidism of the second family lead to more
      marked signs of intrauterine hyperthyroidism. The mother observed marked symptoms
      of fetal and neonatal hyperthyroidism. The bone age at a chronological age of 6
      months was 4-6 years and the neonate showed a mild exophthalmus. We conclude,
      that congenital hyperthyroidism due to constitutively activating TSH receptor
      mutations has to be considered, if hyperthyroidism is not transient but
      persistent, and the parameters of autoimmunity are absent. Constitutively active
      TSH receptor germline mutations lead to different degrees of congenital
      hyperthyroidism. In contrast to patients with Graves' disease, more aggressive
      means of treatment like total thyroidectomy and/or radiation seem to be
      recommendable in cases with severe hyperthyroidism to control the disease.

PMID- 8981020
TI  - Constitutively activating TSH receptor mutations as the cause of toxic thyroid
      adenoma, multinodular toxic goiter and autosomal dominant non autoimmune
      hyperthyroidism.
AB  - cAMP stimulates both the growth and differentiated thyroid function of the
      thyroid gland. In toxic nodules the clinical observation of hyperthyroidism
      together with TSH independent growth of the hot nodule suggests a chronic
      activation of the cAMP cascade. Somatic mutations in a gene of the cAMP
      regulatory cascade leading to constitutive activation of this cascade in toxic
      nodules were first detected in the G protein Gs alpha. Thereafter constitutively
      activating TSH receptor mutations were identified in 20-80% of toxic thyroid
      nodules and in 3 of 6 toxic multinodular goiters. Constitutively activating TSH
      receptor germline mutations are expected to lead to toxic hyperplasia. Sequencing
      of the TSH receptor gene in families with hereditary non autoimmune
      hyperthyroidism led to the identification of constitutively activating TSH
      receptor mutations in 7 families. Moreover, sporadic TSH receptor germline
      mutations have been identified in 3 children with severe congenital nonautoimmune
      hyperthyroidism. Therefore, in cases of clustering of non autoimmune
      hyperthyroidism in families and in cases of sporadic congenital hyperthyroidism
      with thyroid hyperplasia and no evidence for an autoimmune etiology a search for
      TSH receptor gene mutations is necessary to appropriately direct the therapy of
      these patients.

PMID- 8981021
TI  - Plectin and human genetic disorders of the skin and muscle. The paradigm of
      epidermolysis bullosa with muscular dystrophy.
AB  - Recent progress in understanding the molecular organization of the cutaneous
      basement membrane zone (BMZ) has revealed an intricate network of structural
      proteins necessary for stable association of the epidermis to the underlying
      dermis. Molecular genetics of the cutaneous BMZ has also revealed that defects in
      as many as nine distinct genes within the dermal-epidermal junction which result
      in different forms of epidermolysis bullosa (EB), a group of heritable mechano
      bullous disorders. We have recently demonstrated that a variant of EB associated
      with late-onset development of muscular dystrophy (EB-MD, MIM no. 226670) results
      from mutations in the gene encoding plectin (PLEC1), a cytoskeleton associated
      attachment protein present in the hemidesmosomal inner plaque and the sarcolemma
      of the muscle. Consequently, mutations in this multi-functional gene/protein
      system can result in phenotypic manifestations of EB-MD both in the skin and the
      muscle. In this overview, we will summarize the domain organization of plectin
      and the structure of the corresponding gene (PLEC1), as well as the genetic basis
      of EB-MD in families studied thus far. Elucidation of the molecular basis of this
      subtype of EB adds to our understanding of the structural and functional
      complexity of the cutaneous BMZ.

PMID- 8981022
TI  - Tyrosinase may protect human melanocytes from the cytotoxic effects of the
      superoxide anion.
AB  - Reactive oxygen species (ROS) are potentially cytotoxic and several mechanisms
      have evolved to protect against their damaging effects. In melanocytes,
      tyrosinase may have such a role by utilising the superoxide anion (O2-) in the
      production of melanin. In the present study, we have examined the cytotoxic
      effects of O2- and hydrogen peroxide (H2O2) in human melanocytes both before and
      following the activation of tyrosinase. Xanthine oxidase (XO, 5-150 mU.ml-1) and
      glucose oxidase (GO, 0.1-20 mU.ml-1) were used to generate the O2- and H2O2
      respectively, and the cytotoxic effects assessed by measuring cell survival using
      the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium (MTT) assay. 3 h later,
      dose-related decreases in melanocyte survival were seen. Similar experiments with
      keratinocytes and fibroblasts showed that these cells were more resistant to the
      cytotoxic effects of O2- than were the melanocytes. The effect of increasing
      tyrosinase activity was examined by growing the melanocytes in the presence of an
      analogue of melanocyte-stimulating hormone (MSH) Nle4DPhe7 alpha-MSH (10(-8) M),
      for 48 h. This increased tyrosinase activity, melanin content, the ability to
      trap O2- and the resistance of the melanocytes to the cytotoxic effects of this
      ROS, but failed to alter their susceptibility to the damaging effects of
      H2O2.Nle4DPhe7 alpha-MSH had no effect on the resistance of keratinocytes and
      fibroblasts to either O2- or H2O2. After 3 h, XO, as opposed to GO, also
      increased the melanin content of human melanocytes; this effect was not
      accompanied by an increase in tyrosinase activity. The present results suggest
      that tyrosinase may utilise O2- to produce melanin and that this process may
      protect melanocytes from the potentially damaging effects of this ROS.

PMID- 8981023
TI  - Nickel chloride/chlorides of divalent metal interactions in nickel-sensitive
      subjects.
AB  - To verify if the counter-ion Cl- permits the same interactions between nickel and
      divalent metals with physicochemical similarities as the counter-ion SO4- does,
      50 sensitive subjects to nickel sulfate 5% pet. who previously gave positive
      patch test reactions either to 8 mu 1 of aq. nickel sulfate 0.1 M or to 8 mu 1 of
      aq. nickel chloride 0.1 M, or to both, were patch retested simultaneously to 8 mu
      1 of, respectively, aq. nickel sulfate 0.1 M and aq. nickel chloride 0.1 M, and
      to 8 mu 1 of aq. mixed solutions containing, respectively, nickel chloride 0.1
      M+magnesium chloride 0.3 M, nickel chloride 0.1 M+zinc chloride 0.3 M, nickel
      chloride 0.1 M+zinc chloride 0.5 M, nickel chloride 0.1 M+manganese chloride 0.3
      M, and nickel chloride 0.1 M+manganese chloride O.5 M. Whilst 4 subjects gave a
      positive patch test response to only nickel sulphate, 8 gave a positive response
      to nickel chloride alone and the remaining 38 gave a concomitant positive
      response to both. In all subjects who gave positive responses to nickel chloride,
      the chlorides of divalent metals were not able to inhibit or reduce the positive
      reaction. 25 healthy subjects patch tested to both single salts and mixed
      solutions, and all gave negative responses. 9 of the 50 subjects, 4 who
      previously gave positive reactions to only nickel chloride 0.1 M, and 5 with
      concomitant reactions of equal intensity to both nickel chloride and nickel
      sulfate 0.1 M, were patch retested simultaneously to 8 mu 1 of, respectively, aq.
      nickel sulfate 0.1 M, aq. nickel chloride 0.1 M and aq. mixed solutions
      containing nickel sulfate (0.1 M) mixed with sulfates (0.3 M) and nickel chloride
      (0.1 M) mixed with chlorides of Mg, Zn, Mn (0.3 M). Whilst the mixed sulfate
      solutions were able to reduce nickel sulfate, 0.1 M patch test positive
      reactions, those containing chlorides, at all concentrations tested, did not
      inhibit the nickel chloride reactions in any of the subjects. The results of the
      tests to chlorides, compared to those reached on testing to sulfates of the same
      metals, lead us to hypothesize that the anion probably affects the uptake and
      local tissue distribution of the metal, modulating in this way, together with the
      individual cutaneous ligands, its effects.

PMID- 8981024
TI  - Epidermal innervation correlates with severity of photodamage. A quantitative
      ultrastructural study.
AB  - Intraepidermal nerve fibers were studied by electron microscopy in chronically
      photodamaged preauricular skin and in paired sun-protected postauricular sites of
      20 Caucasian women aged 56-70 years. As previously reported, basal keratinocytes
      in the sun-exposed skin showed various degrees of degenerative changes including
      intracellular vacuolar structures and widened intercellular spaces. Neurites were
      frequently closely apposed to basal keratinocytes in preauricular sun-exposed
      skin, but were observed less than 10% as often in sun-protected postauricular
      skin. When degree of epidermal photodamage was quantified by means of the number
      of degenerated keratinocytes per 100 keratinocytes in the basal layer, the number
      of intraepidermal nerve fibers was significantly correlated by linear regression
      analysis to the severity of epidermal photodamage (r = 0.913) independent of
      anatomical sites. These results demonstrate for the first time a correlation
      between degree of epidermal innervation and chronic photodamage and suggest the
      possibility of neural involvement in the pathophysiology and/or repair of
      photodamaged skin.

PMID- 8981025
TI  - Metabolism of topical retinaldehyde and retinol by mouse skin in vivo:
      predominant formation of retinyl esters and identification of 14-hydroxy-4, 14
      retro-retinol.
AB  - We have previously shown that retinaldehyde (RAL), a natural metabolite of beta
      carotene and retinol (ROL), can be used topically in human skin and exerts
      biological activity; it may be a convenient way to deliver multipotential vitamin
      A activity in epidermis. RAL can be converted enzymatically into 2 pathways: one
      leads to ROL (and then retinyl esters), the other to retinoic acid (RA). The aim
      of the present study was 2-fold: (i) to see if RAL is metabolised in vivo when
      topically applied on mouse skin, and (ii) if so, to analyse the occurrence and
      relative importance of the 2 metabolic pathways as compared to ROL. We studied by
      HPLC the metabolites detectable in mouse tail skin upon topical application of
      RAL and ROL. As compared to vehicle-treated controls, RAL-treated mouse skin
      contained low amounts of all-trans RA and 13-cis-RA, whereas ROL content
      increased 10-fold and retinyl esters 30-fold after RAL application. As compared
      to RAL, ROL-treated mouse skin showed no detectable RA, slightly less retinyl
      esters but a significant amount of 14-hydroxy-4, 14-retro-ROL (14-HRR), a
      metabolite not previously reported in the skin. 14-HRR was the predominant polar
      metabolite of ROL. These data indicate that keratinocytes metabolise topical RAL,
      thus confirming the concept of using RAL as a precursor. Both pathways are used
      but in significantly different proportions. Thus, only a low proportion of RAL is
      metabolised into all-trans-RA, which may explain the low irritancy profile of
      topical RAL and supports the concept of a controlled delivery of ligands. That
      keratinocytes predominantly channel RAL into storage forms indicates that RAL
      should also be considered as a convenient way to load the epidermis with vitamin
      A. The detection of 14-HRR, a metabolite not previously reported in skin, that
      promotes growth of B Iymphocytes and activation of T Iymphocytes, suggests
      distinct potentials of topical ROL and RAL.

PMID- 8981026
TI  - Expression, but lack of calcium mobilization by high-affinity IgE Fc epsilon
      receptor I on human epidermal and dermal Langerhans cells.
AB  - In atopic dermatitis (AD) patients, IgE molecules are demonstrated on the surface
      of Langerhans cells (LC). Fc epsilon RI molecules, which are present on the
      surface of LC in AD patients as well as normal individuals, are responsible for
      this binding. In this study, we have investigated phenotypic and functional
      characteristics of Fc epsilon RI on epidermal and dermal cell populations.
      Epidermal and dermal cell suspensions were prepared enzymatically with dispase
      followed by either trypsin or collagenase treatment, respectively. Peripheral
      blood basophils were negatively selected by excluding other leukocytes with
      surface marker staining. Consistent with previous reports, both peripheral blood
      basophils and epidermal LC were positively stained with anti Fc epsilon RI
      monoclonal antibody. In addition, an Fc epsilon RI positive population was
      demonstrated among dermal HLA-DR positive cells. These cells express significant
      amounts of HLA-DR molecules (DRHi) and co-express CD 1 a molecules, which
      identifies them as LC-like dendritic APC of the dermis. No other Fc epsilon RI
      positive population was found in the other dermal DRMid or DR- populations,
      except for a minor DRLo population, presumably mast cells. To analyze whether
      these Fc epsilon RI molecules are signal transducing for LC, intracellular
      calcium mobilization after crosslinking of Fc epsilon RI was measured with flow
      cytometry. Following crosslinking, peripheral blood basophils clearly increased
      intracellular calcium. On the other hand, neither normal epidermal LC nor dermal
      DRHiCD1a + cells changed their intracellular calcium level after Fc epsilon RI
      crosslinking. These data indicate that normal epidermal and dermal LC, but not
      basophils, are resistant to calcium flux following Fc epsilon RI engagement.

PMID- 8981027
TI  - A screening of skin changes, with special emphasis on neurochemical marker
      antibody evaluation, in patients claiming to suffer from "screen dermatitis" as
      compared to normal healthy controls.
AB  - In the present study, facial skin from so-called "screen dermatitis" patients
      were compared with corresponding material from normal healthy volunteers. The aim
      of the study was to evaluate possible markers to be used for future double-blind
      or blind provocation investigations. Differences were found for the biological
      markers calcitonin gene-related peptide (CGRP), somatostatin (SOM), vasoactive
      intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI),
      neuropeptide tyrosine (NPY), protein S-100 (S-100), neuron-specific enolase
      (NSE), protein gene product (PGP) 9.5 and phenylethanolamine N-methyltransferase
      (PNMT). The overall impression in the blind-coded material was such that it
      turned out easy to blindly separate the two groups from each other. However, no
      single marker was 100% able to pin-point the difference, although some were quite
      powerful in doing so (CGRP, SOM, S-100). However, it has to be pointed out that
      we cannot, based upon the present results, draw any definitive conclusions about
      the cause of the changes observed. Whether this is due to electric or magnetic
      fields, a surrounding airborne chemical, humidity, heating, stress factors, or
      something else, still remains an open question. Blind or double-blind
      provocations in a controlled environment are necessary to elucidate possible
      underlying causes for the changes reported in this investigation.

PMID- 8981028
TI  - Exposure of UVB-sensitive mice to immunosuppressive doses of UVB in vivo fails to
      affect the accessory function or the phenotype of draining lymph node dendritic
      cells.
AB  - Following the application of sensitizing chemicals to the skin, hapten-bearing
      Langerhans cells (LC) and possibly other cutaneous dendritic cells (DC) migrate
      to the draining lymph nodes (DLN) of mice and induce the proliferation of antigen
      specific effector T cells. This migration of DC to the DLN is required for the
      induction of primary immune responses. In certain strains of mice, irradiation
      with ultraviolet-B light (UVB) before sensitization results in the suppression of
      contact hypersensitivity responses. In vitro investigations have suggested that
      one influence of UVB is to modify the ability of Langerhans cells (LC) to present
      antigen. In the present investigation, putative UVB-induced alterations in lymph
      node DC in vivo were examined. Lymph node DC were analysed following exposure of
      C3H/HeN mice to an immunosuppressive dose of UVB (1440 J/m2) 48 and 24 h prior to
      skin painting with the sensitizers fluorescein isothiocyanate or oxazolone. In
      functional studies, DC prepared from the DLN of contact sensitized mice were
      examined for their ability to induce hapten-specific secondary T-lymphocyte
      proliferative responses or mixed lymphocyte reactions in vitro. In neither case
      was the activity of DC influenced by local exposure to an immunosuppressive dose
      of UVB. The migration of LC from the epidermis to the draining lymph node in
      response to contact sensitization is associated with increased expression of
      several membrane determinants necessary for effective antigen presentation,
      including intercellular adhesion molecule-1 (ICAM-1; CD54), B7-2 (CD86) and Ia
      antigen. The expression of these molecules was identical on DC isolated from the
      DLN of UVB-irradiated and from control, unirradiated mice. Thus, the
      immunosuppressive effect of UVB on the cutaneous immune system may not
      necessarily reflect changes in the antigen-presenting DC that accumulate in the
      DLN following skin sensitization.

PMID- 8981029
TI  - Mechanism of hydroxyl radical-induced modulation of vascular tone.
AB  - We investigated the effects of hydroxyl radicals (OH) generated by a .OH
      generating system (dihydroxyfumarate [DHF], adenosine diphosphate [ADP], and
      FeCl3) on isolated rabbit aorta suspended in Krebs-Ringer solution. The .OH
      generating system produced a concentration-dependent generation of .OH. .OH
      relaxed rabbit aorta and norepinephrine (NE)-precontracted aorta in a
      concentration-dependent manner. Mannitol completely prevented this relaxation.
      Relaxation was completely absent in preparations denuded of endothelium. The
      relaxant effect was reduced by 62% by an inhibitor of nitric oxide synthesis (NG
      monomethyl-L-arginine), by 58% by an inhibitor of guanylate cyclase (methylene
      blue), by 48% by an inhibitor of cyclooxygenase (indomethacin), and by 83% by an
      adenosine triphosphate (ATP)-sensitive K+ channel blocker (glyburide). The
      inhibition of .OH-induced relaxation by a combination of indomethacin, methylene
      blue, and glyburide was not greater than by each of the individual agents. These
      results indicate that .OH produces a relaxation of the aorta that is completely
      endothelium-dependent and is partly mediated by an endothelium-derived relaxing
      factor (nitric oxide), vasodilatory arachidonic acid metabolites, and an ATP
      sensitive K+ channel.

PMID- 8981030
TI  - Lipid peroxidation and changes in the ubiquinone content and the respiratory
      chain enzymes of submitochondrial particles.
AB  - The relationship between, lipid peroxidation induced by ascorbate and adenosine
      ADP/Fe3+, and its effect on the respiratory chain activities of beef heart
      submitochondrial particles has been investigated. Lipid peroxidation, measured as
      thiobarbituric acid reactive substance formation, resulted in an inhibition of
      the NADH and succinate oxidase activities. Examination of several partial
      reactions of the respiratory chain revealed inactivation primarily of those
      involving endogenous ubiquinone, i.e., NADH- and succinate-ubiquinone1 and
      cytochrome c reductases. Ubiquinol-cytochrome c reductase, measured with reduced
      ubiquinone2 as electron donor, was unaffected. The amount of NADH- or succinate
      reducible cytochrome b in the presence of cyanide was strongly decreased, but
      could be recovered by the addition of antimycin. There occurred a substantial
      decrease of the ubiquinone content in the course of lipid peroxidation, with a
      linear relationship between this decrease and the NADH and succinate oxidase
      activities. The results are consistent with the conclusion that the ubiquinone
      pool undergoes an oxidative modification during lipid peroxidation, to a form
      that can no longer function as a component of the respiratory chain. Lipid
      peroxidation also led to a partial inhibition of the succinate dehydrogenase and
      cytochrome c oxidase activities and a minor decrease of the cytochrome c and
      cytochrome a contents. Reduction of endogenous ubiquinone prevented lipid
      peroxidation as well as the concomitant modification of ubiquinone and
      inactivation of the respiratory chain. These observations suggest that the
      destruction of ubiquinone through lipid peroxidation is the primary cause of
      inactivation of the respiratory chain, and emphasize the antioxidant role of
      ubiquinol in preventing these effects. The possible implications of these
      findings for regulation of the cellular turnover of ubiquinone by the prevailing
      oxidative stress are discussed.

PMID- 8981031
TI  - Chemiluminescence from human polymorphonuclear leukocytes activated with
      opsonized zymosan.
AB  - To prove the mechanism of photon emission during activation of leukocytes, a
      model system of human polymorphonuclear leukocytes (PMNs)-opsonized zymosan (OZ)
      tyrosine (or none) or myeloperoxidase (MPO)-H2O2-tyrosine was employed, and three
      parameters-chemiluminescence yield and intensity, a metabolite such as bityrosine
      (BT), and chemiluminescence spectra-were studied. With the PMN system, the
      luminescence was enhanced by addition of tyrosine, its analogues, or albumin, but
      was inhibited by hydroxyurea, superoxide dismutase (SOD), or NaN3 (an inhibitor
      of MPO), indicating participation of tyrosine phenoxyl radicals, O2.- and MPO in
      the luminescence. With the PMN-OZ-tyrosine system, chemiluminescence yield was
      parallel to the BT formation. These results were essentially the same as those
      obtained with the MPO-H2O2-tyrosine system, except that luminescence from the
      latter system was not inhibited by SOD. When human albumin was exposed to the MPO
      H2O2 system, BT was detected after hydrolysis of the protein in the mixture.
      Judging from the chemiluminescence spectra of activated PMNs and the MPO
      catalyzed tyrosine oxidation, at least two excited species in triplet states-one
      for tyrosine and another for BT-would be generated in these systems. The
      luminescence may originate from the reaction of tyrosine phenoxyl radicals
      (cation radicals) with O2.- and/or peroxidase compound III (Fe...IIIO2.-).

PMID- 8981032
TI  - Evaluation of plasma low molecular weight antioxidant capacity by cyclic
      voltammetry.
AB  - The low molecular weight antioxidants (LMWA) of biological samples include many
      compounds and contribute to the total antioxidant capacity of the system. They
      act as direct chemical scavengers neutralizing, reactive oxygen-derived species
      (ROS), and contribute to the ability of the sample to cope with oxidative stress.
      We propose cyclic voltammetry (CV) as a new method for evaluating the antioxidant
      capacity of plasma-LMWA and the severity of oxidative stress exerted on the
      plasma. It is based on the reducing properties of these molecules. CV has been
      proven to be a simple, sensitive and reliable method. Its tracing does not change
      during storage of frozen plasma for up to six months. We analyzed the CV tracings
      by the oxidation potential E1/2, and the current heights Ia of its anodic
      wave(s). E1/2 indicates the specific component of the LMWA and its ability to
      donate electron(s); Ia indicates the concentration of this component. Two anodic
      waves have been identified in human plasma, at E1/2 = 420 +/- 25 and 920 +/- 25
      mV. Ascorbate (AA) and urate (UA) were identified as major LMWA components of the
      first anodic wave, and were confirmed by HPLC-electrochemical detection. Ia was
      shown to depend linearly on the concentration of either of these LMWA, both in
      buffer and in plasma. Oxidative stress exerted by exposure to peroxyl radicals,
      copper ions and ionizing irradiation caused marked changes in the CV tracing.
      These changes represent corresponding alterations particularly in la, rather than
      in E1/2. The Ia and E1/2 values reflect the antioxidant capacity of the plasma,
      while the change of Ia value represents the severity of the oxidative stress
      induced.

PMID- 8981033
TI  - Peroxidase activation of 4-hydroxytamoxifen to free radicals detected by EPR
      spectroscopy.
AB  - 4-Hydroxytamoxifen is a major metabolite of the antiestrogenic drug tamoxifen
      used in the treatment of women with breast cancer. 4-Hydroxytamoxifen is broken
      down by a horseradish peroxidase/H2O2 system very much more rapidly than
      tamoxifen and causes much greater DNA damage determined by 32P-postlabelling. EPR
      spin trapping of 4-hydroxytamoxifen reaction products in the presence of the free
      radical trap 5,5-dimethyl-1-pyrroline N-oxide, together with glutathione as a
      hydrogen donor, resulted in the generation of a species with the characteristics
      of the glutathione thiyl radical (aN approximately 15.3 G, aH approximately 16.2
      G). Support for the creation of thiyl radicals comes from the close to
      stoichiometric time dependent formation of glutathione disulfide concomitant with
      the loss of glutathione. Similar results were obtained using 4-hydroxytoremifene
      but no radical formation or glutathione loss could be detected using 3
      hydroxytamoxifen (droloxifene). On-line LC-ESI MS analysis of the incubation
      products from 4-hydroxytamoxifen has identified three products with a protonated
      molecular mass of 773, consistent with the formation of dimers of 4
      hydroxytamoxifen. The role that radical mechanisms have in the carcinogenic
      effects of tamoxifen in the endometrium or other target organs of women taking
      this drug remains to be established.

PMID- 8981034
TI  - Influence of age on the release of reactive oxygen species by phagocytes as
      measured by a whole blood chemiluminescence assay.
AB  - Polymorphonuclear and mononuclear phagocytes play an important role in host
      defense, but may also cause tissue injury through excessive inflammation.
      Reactive oxygen species (ROS) are not only directly ore indirectly involved in a
      wide variety of clinical disorders, such as atherosclerosis, reperfusion injury,
      pulmonary toxicity and cancer, but they are also important in the aging process.
      This process is associated with increasing susceptibility to infection. In this
      study we investigated the influence of age and sex on phagocyte activation by
      means of a whole blood chemiluminescence (CL) assay. Circulating phagocyte
      activity was measured in 55 healthy volunteers (24 females, 31 males) aged from 6
      to 92 years. Using an automated luminescence system, phagocytes were stimulated
      by polystyrene beads and Luminol-enhanced CL was determined in terms of peak
      height and peak time in freshly withdrawn, peripheral venous whole blood. An
      extremely significant positive correlation (p < 0.0001) between the maximum of
      light emission after stimulation and increasing age was found. This finding is
      true for the total population of blood phagocytes as well as for a single cell.
      In contrast the time of the appearance of the maximum of light emission showed an
      extremely significant inverse correlation (p < 0.0003) with increasing age. The
      influence of sex on the CL-parameters showed no significant difference between
      women and men. It is concluded that the increased susceptibility of circulating
      phagocytes to oxidative burst in elderly subjects may be the consequence of
      several biological events. Senescent cells express more and also have new
      antigens on their surfaces that trigger an autoimmune response. Cellular
      senescence appears earlier in old organisms. Therefore phagocytes in aging
      individuals may be increasingly involved in their scavenger tasks that grow with
      the catabolic bias in cell turnover. Moreover, atherosclerotic alterations in the
      intima and endothelial lesions are physiologic concomitants of age and may lead
      to a stimulation of circulating phagocytes.

PMID- 8981035
TI  - A comparative study of the redox-cycling of a quinone (rifamycin S) and a
      quinonimine (rifabutin) antibiotic by rat liver microsomes.
AB  - Rifamycin S and rifabutin are clinical drugs used to treat tuberculosis and
      leprosy. The formation of reactive oxygen species during the redox-cycling of
      rifamycin S (quinone) and rifabutin (quinonimine) was evaluated. The semiquinone
      (or semiquinonimine) and hydroquinone (or hydroquinonimine) formed during the
      reduction of the parent molecules by microsomal electron transfer in the presence
      of nicotinamide-adenine dinucleotide phosphate, reduced (NADPH) or nicotinamide
      adenine dinucleotide, reduced (NADH) reoxidizes in air to generate superoxide
      radical and hydrogen peroxide. In the presence of added iron, hydroxyl radicals,
      formed by the Fenton reaction, were detected using 5,5'-dimethyl-1-pyroline-N
      oxide as the spin-trap. Rifamycin S, a quinone, redox cycles more efficiently
      than rifabutin, a quinonimine, as approximately five times the concentration of
      hydroxyl radical adduct of 5,5'-dimethyl-1-pyroline-N-oxide (DMPO) was detected,
      when compared with rifabutin. The NADPH-dependent microsomal production of
      hydroxyl radical in the presence of rifamycin S was somewhat higher than the NADH
      rifamycin S system with most iron chelators. However, with rifabutin, NADH
      dependent microsomal production of hydroxyl radical was higher than that found
      with the NADPH-rifabutin system. An exception was the iron chelator, diethylene
      triamine-pentacetic acid (DTPA), in which NADPH-dependent rates exceeded the
      rates with NADH with both antibiotics. Rat liver sub-mitochondrial particles also
      generated hydroxyl radical in the presence of NADH and either rifamycin S or
      rifabutin. The electron transport chain inhibitors such as rotenone and antimycin
      A enhanced the signal intensity of DMPO-OH, suggesting NADH dehydrogenase
      (complex I) as the major component involved in the reduction of rifamycin S.
      Rifamycin S was shown to be readily reduced to rifamycin SV, the corresponding
      hydroquinone by Fe(II); under similar conditions Fe(II) did not reduce rifabutin.
      Using optical spectroscopy, we determined that rifamycin S forms a complex with
      Fe(II). The stoichiometry of the complex was Fe(rifamycin S)3 in phosphate buffer
      at pH 7.4. Rifabutin did not form a detectable complex with Fe(II). The redox
      cycling of rifamycin S and rifabutin did not cause microsomal lipid peroxidation.
      In fact, the Fe:ATP induced lipid peroxidation was completely inhibited by these
      two molecules. These results indicate that rifamycin S and rifabutin can interact
      with rat liver microsomes to undergo redox-cycling, with the subsequent
      production of hydroxyl radicals when iron complexes are present. Compared to
      NADPH, NADH is almost as effective (rifamycin S) or even more effective
      (rifabutin) in promoting these interactions. These interactions may play a role
      in the hepatotoxicity associated with the use of these antibiotics.

PMID- 8981036
TI  - Oxygen-induced embryopathy and the significance of glutathione-dependent
      antioxidant system in the rat embryo during early organogenesis.
AB  - We investigated the effect of glutathione (GSH)-dependent antioxidant system
      against hydrogen peroxide (H2O2) formation in oxygen-induced embryopathy.
      Exposure of rat embryos to a high concentration of oxygen (20%) during early
      neurulation (day 9 to 10) significantly increased the incidence of neural tube
      defects compared with control embryos (10% vs 0%, p < 0.01) exposed to a low O2
      concentration (5%). The concentration of GSH in 20% O2-exposed embryos was
      significantly reduced compared with that in control embryos (10.68 +/- 0.72 vs
      12.34 +/- 0.65 nmol/mg protein, p < 0.001). The activity of gamma
      glutamylcysteine synthetase (gamma-GCS), the rate-limiting GSH synthesizing
      enzyme increased in 20% O2-exposed embryos (24.83 +/- 0.71 vs 21.00 +/- 0.94
      microunits/mg protein). Increased activity of gamma-GCS was associated with
      increased expression of gamma-GCS mRNA. Substantial increases were also observed
      in the activities of glutathione peroxidase (GPX) and glutathione S-transferase
      (GST) in 20% O2-exposed embryos. The formation of intracellular H2O2, measured by
      flow cytometer using 2',7'-dichlorofluorescein diacetate (DCFH-DA), increased in
      isolated embryonic cells of 20% O2-exposed embryos. The addition of buthionine
      sulfoxamine (BSO), a specific inhibitor of gamma-GCS, to culture media exposed to
      20% O2 produced a marked decrease in the concentration of GSH in association with
      a further increase in the incidence of embryonic malformations (24.4% vs. 10%, P
      < 0.01). The addition of 2.0 mM GSH ester to culture media exposed to 20% O2
      prevented the development of embryonic malformations through the restoration of
      normal GSH contents and reduction of H2O2. Our results demonstrated that oxygen
      induced embryonic malformations were induced by increased production of H2O2 in
      the presence of an immature free radical scavenger system. We suggest that
      impaired responsiveness of the GSH dependent antioxidant system against oxidative
      stress plays a crucial role in oxygen-induced embryopathy.

PMID- 8981037
TI  - Cholesterol: a two-edged sword in brain aging.
AB  - Previous research from several laboratories has indicated that cholesterol (CHO)
      accumulates in neuronal membranes and alters their structural and signal
      transduction (ST) properties during aging. The possible reasons for these
      increases in membrane CHO have not been specified. However, present findings
      suggest that such accumulation may actually serve to protect neuronal tissue from
      oxidative damage. Striatal slices (6, 24 month rats) were preincubated in 1 mM
      CHO (30 min) followed by incubation with H2O2 (10 microM, 30 min). The slices
      were then either superfused with 30 mM KCl in the presence or absence of 500
      microM oxotremorine (Ox), and K(+)-evoked dopamine release (K(+)-ERDA) examined
      or assessed for carbachol-stimulated low K(m) GTPase activity. The results
      indicated that CHO incubation prior to H2O2 in either age group was effective in
      preventing H2O2 reductions in both non-Ox-enhanced K(+)-ERDA and Ox conditions,
      as well as sodium nitroprusside (SNP 150 microM)-induced decreases in K(+)-ERDA.
      In addition, H2O2-induced deficits in carbachol-stimulated low K(m) GTPase
      activity were reduced in the striatal tissue from the old animals pretreated with
      CHO. However, if the slices were incubated in H2O2 prior to CHO exposure, CHO
      enhanced the H2O2 effects in the tissue from the old animals. Thus, depending
      upon the order of exposure, CHO functioned to enhance or retard the effects of
      oxidative stress, in an age-dependent manner.

PMID- 8981038
TI  - Optimal time and dosage of phenyl N-tert-butyl nitrone (PBN) for the inhibition
      of nitric oxide synthase induction in mice.
AB  - We have previously reported that phenyl N-tert-butyl nitrone (PBN) inhibits the
      induction of inducible nitric oxide synthase (iNOS) and, thus, prevents the
      overproduction of nitric oxide (NO), resulting in the reduction of endotoxin
      mediated death in mice. In this study, to examine the effect of PBN in detail, we
      investigated the dose- and administration-timing dependence of PBN on endotoxin
      induced NO generation in mice. NO generation was monitored in the mouse liver
      after administration of lipopolysaccharide (LPS) by the in vivo NO-spin trapping
      method using the iron complex of N-methyl-D-glucamine dithiocarbamate (MGD) as a
      spin trap, followed by ex vivo EPR measurement of the liver tissue. PBN was
      effective in reducing liver NO generation monitored 6 h after endotoxin injection
      when it was administered shortly before or after LPS injection. The maximum
      inhibition of liver NO was obtained when PBN was administered 30 min before LPS
      injection. ID50 for the inhibition was estimated to be approximately 200 mg/kg
      when the LPS dose of 50 mg/kg was used. Expression of mRNA for iNOS in the liver
      as estimated by reverse transcription polymerase chain reaction was decreased
      when PBN was given 30 min before LPS injection, indicating that the reduction of
      expression of iNOS protein by PBN, which has been shown previously, is at least
      in part caused by a decrease in mRNA expression.

PMID- 8981039
TI  - Induction of oxidative stress by chronic administration of sodium dichromate
      [chromium VI] and cadmium chloride [cadmium II] to rats.
AB  - Recent studies have demonstrated that both chromium (VI) and cadmium (II) induce
      an oxidative stress, as determined by increased hepatic lipid peroxidation,
      hepatic glutathione depletion, hepatic nuclear DNA damage, and excretion of
      urinary lipid metabolites. However, whether chronic exposure to low levels of
      Cr(VI) and Cd(II) will produce an oxidative stress is not shown. The effects of
      oral, low (0.05 LD50) doses of sodium dichromate [Cr(VI); 2.5 mg/kg/d] and
      cadmium chloride [Cd(II); 4.4 mg/kg/d] in water on hepatic and brain
      mitochondrial and microsomal lipid peroxidation, excretion of urinary lipid
      metabolites including malondialdehyde, formaldehyde, acetaldehyde and acetone,
      and hepatic nuclear DNA-single strand breaks (SSB) were examined in female
      Sprague-Dawley rats over a period of 120 d. The animals were treated daily using
      an intragastric feeding needle. Maximum increases in hepatic and brain lipid
      peroxidation were observed between 60 and 75 d of treatment with both cations.
      Following Cr(VI) administration for 75 d, maximum increases in the urinary
      excretion of malondialdehyde, formaldehyde, acetaldehyde, and acetone were 2.1-,
      1.8-, 2.1-, and 2.1-fold, respectively, while under the same conditions involving
      Cd(II) administration approximately 1.8-, 1.5-, 1.9-, and 1.5-fold increases were
      observed, respectively, as compared to control values. Following administration
      of Cr(VI) and Cd(II) for 75 d, approximately 2.4- and 3.8-fold increases in
      hepatic nuclear DNA-SSB were observed, respectively, while approximately 1.3- and
      2.0-fold increases in brain nuclear DNA-SSB were observed, respectively. The
      results clearly indicate that low dose chronic administration of sodium
      dichromate and cadmium chloride induces an oxidative stress resulting in tissue
      damaging effects that may contribute to the toxicity and carcinogenicity of these
      two cations.

PMID- 8981040
TI  - Generation of reactive oxygen species during interaction of diesel exhaust
      particle components with NADPH-cytochrome P450 reductase and involvement of the
      bioactivation in the DNA damage.
AB  - Since the toxicity of diesel exhaust particles (DEP) after intratracheal
      injection, was suppressed by pretreatment with superoxide dismutase (SOD)
      modified with polyethylene glycol (Sagai et al. Free Rad. Biol. Med. 14: 37-47;
      1993), the possibility that superoxide could be enzymatically and continuously
      generated from diesel exhaust particles (DEP), was examined. Nicotinamide-adenine
      dinucleotide phosphate, reduced (NADPH) oxidation was stimulated during
      interaction of a methanol extract of DEP with the Triton N-101 treated microsomal
      preparation of mouse lung whereas the cytosolic fraction was less active,
      suggesting that DEP contains substrates for NADPH-cytochrome P450 reductase (EC
      1.6.2.4, P450 reductase) rather than DT-diaphorase. When purified P450 reductase
      was used as the enzyme source, the turnover value was enhanced approximately 260
      fold. Quinones appeared to be served as substrate for P450 reductase because
      reaction was inhibited by addition of glutathione (GSH) to form those GSH adduct
      or pretreatment with NaBH4 to reduce those to the hydroxy compounds although a
      possibility of nitroarenes as the alternative substrates cannot be excluded. A
      methanol extract of DEP (37.5 micrograms) caused a significant formation of
      superoxide (3240 nmol/min/mg protein) in the presence of P450 reductase. Electron
      spin resonance (ESR) experiments revealed that hydroxyl radical was formed as
      well. The reactive species generated by DEP in the presence of P450 reductase
      caused DNA scission which was reduced in the presence of superoxide dismutase
      (SOD), catalase, or hydroxyl radical scavenging agents. Taken together, these
      results indicate that DEP components, probably quinoid or nitroaromatic
      structures, that appear to promote DNA damage through the redox cycling based
      generation of superoxide.

PMID- 8981041
TI  - Peroxynitrite-induced apoptosis in T84 and RAW 264.7 cells: attenuation by L
      ascorbic acid.
AB  - The free radicals nitric oxide and superoxide react to form peroxynitrite (ONOO
      ), a potent cytotoxic oxidant. This study was designed to evaluate whether
      addition of L-Ascorbic acid (AsC) into the culture medium decreases peroxynitrite
      induced apoptosis in human intestinal epithelial (T84) and murine macrophage (RAW
      264.7) cell lines. In Experiment 1, T84 and RAW 264.7 cells were divided in two
      protocols: (1) treated with 100-300 microM ONOO- and incubated for 4 h, and (2)
      treated with 10-100 microM ONOO- and incubated overnight (14 h). In Experiment 2,
      T84 and RAW 264.7 cells were treated with 300 microM ONOO- and 500 microM AsC and
      incubated for 4 h. In Experiment 3, T84 and RAW 264.7 cells were preincubated for
      2 h with 500 microM AsC then exposed to 300 microM ONOO- for 4 h. Cell viability
      (necrosis) was assessed by trypan blue dye exclusion. Apoptosis was quantified
      with a cell death detection ELISA assay. In the 4 h protocol, ONOO- induced
      apoptosis in T84 and RAW 264.7 cells, at levels of 100-300 microM. Concentrations
      of ONOO- greater than 300 microM caused necrosis. In contrast, extension of the
      protocol to 14 h indicated that ONOO- induced apoptosis at lower concentrations
      (50;-75 microM), with concentrations > 75 microM resulting in necrosis. AsC
      administered to the media or with preincubation plus washout, decreased
      peroxynitrite-induced apoptosis in T84 and RAW 264.7 cells. These results
      indicate that ONOO- may contribute to the pathophysiology of gut inflammation by
      promoting cell death and ascorbic acid may protect against peroxynitrie-induced
      damage.

PMID- 8981042
TI  - Endogenous natural killer enhancing factor-B increases cellular resistance to
      oxidative stresses.
AB  - Natural killer-enhancing factor (NKEF) was identified and cloned on the basis of
      its ability to increase NK cytotoxicity. Two genes, NKEF-A and -B, encode NKEF
      proteins and sequence analysis presented suggests that each belongs to a highly
      conserved family of antioxidants. To examine the antioxidant potential of NKEF,
      we transfected the coding region of NKEF-B cDNA into the human endothelial cell
      line ECV304. The stable transfectant, B/1, was found to overexpress NKEF-B gene
      transcript and protein. We subjected B/1 to oxidative stress by either culturing
      them with glucose oxidase (GO), which continuously generates hydrogen peroxide,
      or by direct addition of hydrogen peroxide. We found that B/1 cells were more
      resistant than control cell lines. Resistance to hydrogen peroxide was originally
      thought to be mediated mainly by catalase and the glutathione cycle. Therefore,
      we used inhibitors to block the two pathways and found that B/1 cells were more
      resistant to oxidative stress than control cells when we used inhibitors to
      preblock either pathway. We also examined the cellular inflammatory responses to
      oxidized low-density lipoprotein (LDL) and bacterial lipopolysaccharide (LPS) by
      measuring monocyte adhesion to endothelial cells in vitro and found that B/1
      cells were resistant to such responses. Lastly, we found that B/1 cells were more
      resistant to a novel chemotherapeutic agent CT-2584, which appears to kill tumor
      cells by stimulating production of reactive oxygen intermediates in mitochondria.
      These results demonstrate that the NKEF-B is an antioxidant that protects cells
      from oxidative stress, chemotherapy agents, and inflammation-induced monocyte
      adhesion. Furthermore, its expression may mediate cellular responses to
      proinflammatory molecules.

PMID- 8981043
TI  - Effects of acute prolonged exercise on-serum and LDL oxidation and antioxidant
      defences.
AB  - We investigated the acute effects of long-distance running on oxidation of lipids
      and antioxidant functions in LDL and serum. Eight trained male runners who
      participated in a 31-km run and 22 male keep-fit runners who participated in a
      marathon run were enrolled into the study. Venous blood samples were taken before
      and immediately after the exercise. There were no changes in LDL diene
      conjugation (LDL-DC) or LDL antioxidant potential (LDL-TRAP) during the
      exercises. Serum (S-) TRAP and S-alpha-tocopherol rose during the 31-km run (by
      22%, p = .0005, and by 29%, p = .011, respectively), and during the marathon (by
      16%, p = .0014, and by 7%, p = .031, respectively). S-DC rose during the 31-km
      run (by 9%, p = .0026), but not during the marathon (p = .14). Preexercise and
      postexercise S-alpha-tocopherol correlated positively with pre and postexercise S
      TRAP in the marathon run (r = .473, 95% CI 0.064 to 0.746, and r = .524, 95% CI
      0.131 to 0.774, respectively). Thus, the paradoxical exercise-associated increase
      in S-TRAP is, at least in part, explained by a simultaneous rise in S-alpha
      tocopherol concentration. However, acute exercise does not change LDL-DC or LDL
      TRAP concentrations.

PMID- 8981044
TI  - Hydrogen peroxide (H2O2) increases the steady-state mRNA levels of
      collagenase/MMP-1 in human dermal fibroblasts.
AB  - Reactive oxygen species (ROS) have been shown to be important messenger molecules
      in the induction of several genes. In human dermal fibroblasts the herbicide
      paraquat (PQ2+) was used to induce intracellular oxidative stress that was
      modulated by the inhibition of copper, zinc superoxide dismutase (Cu,ZnSOD),
      glutathione peroxidase (GSHPx), catalase, and blocking of the Fenton reaction.
      Interstitial collagenase (MMP-1) mRNA increased time dependently for up to 72 h
      following paraquat treatment. A correlation with the translation of MMP-1 could,
      however, only be detected up to 24 h, indicating an uncoupling of transcription
      and translation. Interleukin-1 alpha and beta mRNA showed two peaks at 6 h and 72
      h. The inhibition of catalase by aminotriazol (ATZ), inhibition of GSHPx by
      buthionine sulfoximine (BSO), and blocking the Fenton reaction by the iron
      chelator desferrioxamine (DFO) in concert led to an increase in steady-state MMP
      1 mRNA levels, possibly dependent on intracellular H2O2 increase. This combined
      treatment potentiated MMP-1 mRNA induction up to 6.5-fold compared to paraquat
      treated controls. Furthermore, exogenously added H2O2 caused an increase in MMP-1
      mRNA levels. In contrast, inhibition of Cu,ZnSOD by diethyldithiocarbamate (DDC),
      leading to diminished H2O2 production from O2.-, decreased MMP-1 mRNA induction.
      Collectively, our data provide evidence that H2O2 is an important intermediate in
      the downstream signalling pathway finally leading to the induction of increased
      steady state MMP-1 mRNA levels. The synthesis of MMPs may contribute to
      connective tissue damage in vivo related to photoaging, inflammatory diseases,
      and tumor invasion.

PMID- 8981045
TI  - Increase in gamma-glutamyltransferase by glutathione depletion in rat type II
      pneumocytes.
AB  - The purpose of our study was to investigate the effect of oxidative stress or
      intracellular glutathione (GSH) depletion on gamma-glutamyltransferase (gamma-GT)
      activity in cultured type II pneumocytes. Twenty-four hours after isolation,
      primary cultures of rat type II pneumocytes were preincubated with one of four
      compounds: 15, 30, 60, 125, 250 microM L-buthionine-[SR]-sulfoximine (BSO) for 3
      h; 100, 200, 400, 800 microM tertiary-butylhydroperoxide (t-BOOH) for 45 min; 10,
      25, 50, 100 microM menadione for 15 min; 100, 1000 microM paraquat for 1 h. GSH
      levels, H2O2 and O2.- generation were measured immediately after the incubation,
      gamma-GT activity and GSH levels also up to 24 h or 48 h later. Exposure to BSO
      led to a persistent GSH depletion without increase in H2O2 or O2.- production,
      together with a dose and time-dependent increase (doubling) of gamma-GT activity
      with a nonsignificant increase in gamma-GT mRNA expression 24 h after exposure to
      BSO. Exposure to 100 microM menadione, which increased H2O2 production, decreased
      gamma-GT activity. t-BOOH or paraquat did not give rise to a measurable increase
      in H2O2 or O2.-. Paraquat did not affect initial GSH levels, but increased GSH
      and decreased gamma-GT activity 24 h later. t-BOOH (400 and 800 microM) initially
      decreased GSH, and tended to increase GSH 24 h later, 100 and 200 microM
      increased gamma-GT activity 24 h later, but 800 microM decreased it. Restoration
      of intracellular GSH levels by addition of GSH to the culture medium completely
      prevented the increase in gamma-GT activity by BSO, while the addition of
      catalase or DMTU had no effect. We conclude that at least two effects are
      operating upon gamma-GT activity: GSH depletion seems to increase gamma-GT
      activity, while exposure to compounds generating oxidative stress correlates with
      a decrease in gamma-GT activity.

PMID- 8981046
TI  - Cytosolic and mitochondrial systems for NADH- and NADPH-dependent reduction of
      alpha-lipoic acid.
AB  - In cellular, tissue, and organismal systems, exogenously supplied alpha-lipoic
      acid (thioctic acid) has a variety of significant effects, including direct
      radical scavenging, redox modulation of cell metabolism, and potential to inhibit
      oxidatively-induced injury. Because reduction of lipoate to dihydrolipoate is a
      crucial step in many of these processes, we investigated mechanisms of its
      reduction. The mitochondrial NADH-dependent dihydrolipoamide dehydrogenase
      exhibits a marked preference for R(+)-lipoate, whereas NADPH-dependent
      glutathione reductase shows slightly greater activity toward the S(-)-lipoate
      stereoisomer. Rat liver mitochondria also reduced exogenous lipoic acid. The rate
      of reduction was stimulated by substrates which increased the NADH content of the
      mitochondria, and was inhibited by methoxyindole-2-carboxylic acid, a
      dihydrolipoamide dehydrogenase inhibitor. In rat liver cytosol, NADPH-dependent
      reduction was greater than NADH, and lipoate reduction was inhibited by
      glutathione disulfide. In rat heart, kidney, and brain whole cell-soluble
      fractions, NADH contributed more to reduction (70-90%) than NADPH, whereas with
      liver, NADH and NADPH were about equally active. An intact organ, the isolated
      perfused rat heart, reduced R-lipoate six to eight times more rapidly than S
      lipoate, consistent with high mitochondrial dihydrolipoamide dehydrogenase
      activity and results with isolated cardiac mitochondria. On the other hand,
      erythrocytes, which lack mitochondria, somewhat more actively reduced S- than R
      lipoate. These results demonstrate differing stereospecific reduction by intact
      cells and tissues. Thus, mechanisms of reduction of alpha-lipoate are highly
      tissue-specific and effects of exogenously supplied alpha-lipoate are determined
      by tissue glutathione reductase and dihydrolipoamide dehydrogenase activity.

PMID- 8981047
TI  - Comparison of Zn and vitamin E for protection against hyperoxia-induced lung
      damage.
AB  - The objective of the present study was to demonstrate an antioxidant function for
      Zn in vivo by comparing the efficacy of Zn or Vitamin E without additional energy
      intake for protection of Zn-deficient (ZnDF) or energy-restricted (ER) rats from
      hyperoxia-induced lung damage. Zn (200 mumol ZnCl2/kg b.wt.) or Vitamin E (100 mg
      alpha-tocopherol/kg b.wt.) was injected IP before exposure to 85% oxygen or air
      for 5 d. During the exposure period, all injected ZnDF or ER rats were restricted
      to 5 g Zn-deficient or Zn-adequate diet/day, respectively, the amount of diet
      consumed by the untreated ZnDF or ER rats. We clearly demonstrated that injection
      of Zn without additional energy intake can protect ZnDF and ER rats from
      hyperoxia-induced lung damage assessed by the histopathological scoring system
      and magnetic resonance imaging (MRI). Vitamin E was not as effective as Zn in
      either ZnDF or ER rats for preventing hyperoxia-induced lung damage. Zn injection
      did not exert its antioxidant effect through increased lung CuZn-superoxide
      dismutase activity or metallothionein. This difference in the effectiveness of
      Vitamin E and Zn for hyperoxic protection in lung injury may be due to the
      specificity of antioxidant function, i.e., vitamin E inhibits oxidation of
      membrane lipids and Zn protects sulfhydryl groups of proteins.

PMID- 8981048
TI  - Down-regulation of mammalian mitochondrial RNAs during oxidative stress.
AB  - We have identified an RNA species that appears to be induced by oxidative stress
      in hamster HA-1 fibroblasts using the differential display technique, but instead
      is found to be degraded when evaluated by Northern blot hybridization. Cloning
      and subsequent sequencing identified the partially degraded RNA as 16S ribosomal
      RNA (rRNA), a major component of mitochondrial ribosomes. Degradation, and
      associated decreases in the levels of the mature- and precursor-species of 16S
      rRNA, appear to be dependent upon calcium, but not cytoplasmic protein synthesis
      nor nuclear transcription. Other decreased mitochondrial RNAs were also
      identified, including 12S rRNA, NADH dehydrogenase subunit 6, ATPase subunit 6,
      and cytochrome oxidase subunits I and III. A significant part of many, if not
      all, of these RNA decreases was due to degradation. As compared with 16S rRNA,
      significantly less degradation was observed for cytoplasmic 28S/18S rRNAs, even
      at very high peroxide concentration. Analysis of 21 cytoplasmic mRNAs revealed
      little or no decrease in mature band signal in response to peroxide, and several
      cytoplasmic mRNAs were actually up-regulated. Thus, a preferential down
      regulation of mitochondrial RNAs occurs in HA-1 fibroblasts in response to
      hydrogen peroxide. Subcellular fractionation analysis, using 16S rRNA degradation
      as a gauge, indicates that this down-regulation is specific to mitochondria. The
      down-regulation of mitochondrial RNAs may represent a general mechanism by which
      cells protect themselves against oxidative stress.

PMID- 8981049
TI  - Scavenging of reactive oxygen species by a glycolipid fraction of Mycobacterium
      avium serovar 2.
AB  - Previous experiments indicated that MIF-A3, a peptidoglycolipid extracted from
      Mycobacterium avium serovar 2 (Mycobacterium paratuberculosis 18), inhibits the
      killing of Candida albicans by activated bovine peripheral blood-derived
      macrophages and murine thioglycollate-elicited peritoneal macrophages in vitro.
      Subsequent in vitro data from our laboratory indicated that this reduction in
      killing may be related to the ability of MIF-A3 to scavenge reactive oxygen
      species (ROS). In this study we examined this hypothesis directly by determining
      if MIF-A3 reduced exogenous H2O2-induced candidacidal activity. When Candida
      albicans was incubated with H2O2 (4 mM) alone, colony-forming units/ml x 10(4)
      (CFU/ml) were 0.4 +/- 0.1 (mean +/- SE, n = 4) as compared to 11.3 +/- 2.0 CFU/ml
      in control (untreated) cultures (p < .05). The addition of catalase at
      concentrations > or = 6.8 U/ml, completely blocked the fungicidal effect of H2O2.
      However, reducing the amount of catalase from 6.8 U/ml to 3.4 U/ml resulted in a
      loss of scavenging activity, which was associated with a 50% increase in H2O2
      mediated killing. Substituting MIF-A3 (400 micrograms/ml) for catalase, also
      reduced H2O2-induced fungicidal activity. In the absence of MIF-A3, H2O2 reduced
      Candida albicans to less than 10(3) CFU/ml. However, in the presence of MIF-A3
      the CFU/ml of Candida albicans increased 7.5-fold. Based on concentration
      response curves of H2O2 inhibition vs. increasing amounts of catalase we
      determined that the relative inhibitory capacity of the MIF-A3 (400
      micrograms/ml) was approximately 1.0 U/ml "catalase equivalents." These findings
      provide direct evidence that MIF-A3 can scavenge H2O2, and reduce H2O2-induced
      killing of Candida albicans.

PMID- 8981051
TI  - The importance of L-arginine metabolism in melanoma: an hypothesis for the role
      of nitric oxide and polyamines in tumor angiogenesis.
AB  - There is a worldwide increase in the incidence of melanoma. Without treatment,
      melanomas can progress to metastatic disease and result in death. It is now
      accepted that for a tumor to grow, non-tumorous host tissue must form blood
      vessels in and around the tumor. Tumor cells and blood vessels must form a highly
      regulated system whereby endothelial cells can be switched from a resting state
      to one of rapid growth. Tumor cells have been shown to produce diffusible
      angiogenic regulatory molecules. Nitric oxide [NO] and polyamines [PA] have been
      implicated in the angiogenic process. This paper hypothesizes that NO and PA
      regulate melanoma angiogenesis differently. During early stages of malignant
      melanoma an increase in PA synthesis is expected to promote endothelial cell
      proliferation and therefore angiogenesis. NO is expected to be maintained at low
      levels. During the vascular stage of malignant melanoma, NO synthesis is
      hypothesized to be elevated which will decrease endothelial cell proliferation
      and maintain a vasodilator tone in and around the tumor. PA concentrations are
      expected to be lower. A regulatory link between NO and PA may be involved in the
      maintenance of tumor homeostasis. The regulation of L-arginine metabolism in
      tumor angiogenesis requires investigation as it may lead to novel selective
      therapeutic interventions in cancer therapy.

PMID- 8981050
TI  - Paraquat-induced formation of leukotriene B4 in rat lungs: modulation by N
      acetylcysteine.
AB  - The present work is focused on the formation of the inflammatory mediator
      leukotriene B4 (LTB4) in the lungs of paraquat (PQ)-intoxicated rats. The levels
      of LTB4 and the number of neutrophils in lung lavages of PQ-intoxicated rats,
      measured 12 h after 30 mg/kg PQ, increased significantly compared with those of
      control animals; administration of 50 mg/kg IP N-acetylcysteine (NAC), 8 h after
      PQ, inhibited this effect. The release of LTB4 from alveolar macrophages (AM) or
      alveolar epithelial type II cells from healthy animals incubated with PQ and/or
      NAC did not offer' an explanation for the effect of these chemicals on LTB4 in
      the bronchoalveolar lavage fluid (BALF). The PQ-enhanced, NAC-inhibited release
      of arachidonic acid (AA) by alveolar epithelial type II cells did, however,
      explain our in vivo results, when one assumes that the AM synthesize their 5
      lipoxygenase products from alveolar epithelial cell-derived AA, an hypothesis
      demonstrated already by other researchers.

PMID- 8981052
TI  - Platelet-derived growth factor (PDGF): actions and mechanisms in vascular smooth
      muscle.
AB  - 1. PDGF is a highly hydrophilic cationic glycoprotein (M(r) 28-35kDa) produced by
      platelets, monocyte/macrophages, endothelial cells and vascular smooth muscle
      cells under some conditions. 2. Since its original description, PDGF has
      attracted much attention and it is currently believed to play a role in
      atherosclerosis and other vascular pathologies. 3. This review describes the
      vascular biology of PDGF. It particularly focuses on recent findings regarding
      the intracellular signals activated by PDGF in the context of vascular smooth
      muscle cell proliferation, migration and, contraction.

PMID- 8981053
TI  - Basis of the antiseizure action of phenytoin.
AB  - 1. Phenytoin has been used with much clinical success against all types of
      epileptiform seizures, except petit mal epilepsy, for over 50 years. Its
      mechanism of action, however, is still open to interpretation. 2. Several
      potential targets for phenytoin action have been identified within the central
      nervous system. These include the Na-K-ATPase, the GABAA receptor complex,
      ionotropic glutamate receptors, calcium channels and sigma binding sites. 3. To
      date, though, the best evidence hinges on the inhibition of voltage-sensitive Na+
      channels in the plasma membrane of neurons undergoing seizure activity. Quieter
      nerve cells are far less affected. Moreover, the fact that phenytoin also has
      important cardiac antiarrhythymic effects and can inhibit Na+ influx into cardiac
      cells supports the idea that the primary target of phenytoin is, indeed, the Na+
      channel.

PMID- 8981055
TI  - NANC neural control of airway smooth muscle tone.
AB  - 1. This review addresses the functional role of the nonadrenergic, noncholinergic
      (NANC) neural response in the control of airway smooth muscle tone. 2. Functional
      data from guinea pig airways in vitro indicate that the level of basal smooth
      muscle tone determines the direction and magnitude of the NANC neural response
      such that it can stabilise tone. 3. The NANC stabilising effect on tone is
      adjustable through variation in impulse frequency and the NANC stabilising effect
      is also powerful; it can abolish near-maximum differences in tone. 4. Cholinergic
      activation increases the level towards which the NANC responses tend to adjust
      tone. 5. Adrenergic activation reduces the level towards which the NANC responses
      tend to adjust tone via beta-adrenoceptors. 6. NANC neural activation, with or
      without simultaneous adrenergic or cholinergic activation, can stabilise tone at
      low, intermediate or high levels with a high degree of accuracy. 7. Evidence from
      other investigators on effects of putative NANC neurotransmitters supports the
      idea of functional interactions within the NANC system in the airways. 8. It
      remains to be confirmed whether or not NANC responses play a stabilising role in
      the control of airway smooth muscle tone in vivo and in higher mammals.

PMID- 8981054
TI  - The dermorphin peptide family.
AB  - 1. In 1980, the skin of certain frogs belonging to the genus Phyllomedusinae was
      found to contain two new peptides that proved to be selective mu-opioid agonists.
      Given the name dermorphins, these were the first members of a peptide family that
      in the past 15 years has grown to reach a total of seven naturally occurring
      peptides and nearly 30 synthetic analogs. 2. Dermorphin peptides are potent
      analgesics in rodents and primates, including man. Some dermorphins can enter the
      blood-brain barrier and produce central antinociception after peripheral
      administration. 3. The dermorphin family also includes mu 1-opioid receptor
      selective agonists that produce intense opioid analgesia, but stimulate pulmonary
      ventilation. 4. Experiments in rats and mice chronically exposed to dermorphins
      have shown that not only do they have higher antinociceptive efficacy and potency
      than morphine, but they are also less likely than morphine to produce tolerance,
      dependence and opiate side effects.

PMID- 8981056
TI  - Perfluorodecanoic acid as a useful pharmacologic tool for the study of peroxisome
      proliferation.
AB  - The phenomena of peroxisome proliferation in rodent liver has received
      considerable attention due to its association with hepatocellular carcinoma.
      Chemicals that cause peroxisome proliferation include several structurally
      unrelated hypolipidemic drugs, phthalate esters and halogenated solvents. The
      mechanism by which peroxisome proliferators exert their beneficial
      (hypolipidemia) as well as their toxic (cancer) effects is still largely unknown.
      Perfluorodecanoic acid (PFDA) is a potent peroxisome proliferator in rodent liver
      that resembles other members of this chemical class in many aspects, including
      its effects on gene expression and fatty acid metabolism. However, there are many
      dissimilarities between PFDA and hypolipidemic peroxisome proliferators that have
      not been extensively explored. PFDA is unlike other peroxisome proliferators in
      parent compound metabolism, hypolipidemia, and tumor promotion. The present
      review article will discuss what is currently known about PFDA and how it may be
      utilized to dissect the mechanism of action of an important group of
      hypolipidemic drug and environmental pollutant, the peroxisome proliferators.

PMID- 8981057
TI  - Volume-activated Cl- channels.
AB  - 1. An increase in cell volume activates, in most mammalian cells, a Cl- current,
      ICl,vol. This current is involved in a variety of cellular functions, such as the
      maintenance of a constant cell volume, pH regulation, and control of membrane
      potential. It might also play a role in the regulation of cell proliferation and
      in the processes that control transition from proliferation to differentiation.
      This review focuses on various aspects of this current, including its biophysical
      characterisation and its functional role for various cell processes. 2. Volume
      activated Cl- channels show all outward rectification. Iodide is more permeable
      than chloride. In some cell types, ICl,vol inactivates at positive potentials.
      Single channel conductance can be divided mainly into two groups: small (< 5 pS)
      and medium conductance channels (around 50 pS). 3. The pharmacology and
      modulation of these channels are reviewed in detail, and suggest the existence of
      an heterogeneous family of multiple volume-activated Cl- channels. 4. Molecular
      candidates for this channel (i.e. ClC-2, a member of the ClC-family of voltage
      dependent Cl- channels, the mdr-1 encoded P-glycoprotein, the nucleotide
      sensitive pICln protein and phospholemman) will be discussed.

PMID- 8981058
TI  - Tau protein after delta-9-tetrahydrocannabinol in a human neuroblastoma cell
      line.
AB  - 1. A human neuroblastoma cell line, SH-SY5Y, was used to determine the effects of
      delta-9-tetrahydrocannabinol (THC) on microtubule-associated tau protein. 2.
      After 48-hr treatment, THC (10(-9) M) decreased 50 kD tau protein in the
      cytoplasmic (supernatant) fraction, and in the membrane (pellet) fraction the
      drug (10(-7) M) also decreased 50 kD tau protein. 3. This reduction in tau
      protein was accompanied by a 27% reduction (P < 0.05) in the membrane (pellet)
      total protein after (10(-7) M) THC and a 28% increase (P < 0.02) in cytoplasmic
      (supernatant) total protein after 10(-9) M THC.

PMID- 8981059
TI  - Hypochlorous acid and its pharmacological antagonism: an update picture.
AB  - 1. Some biochemical and pathophysiological aspects of hypochlorous acid (as major
      oxidant species produced by activated white blood cells) are discussed. 2.
      Moreover, we have discussed the problem of the pharmacological scavenging of
      hypochlorous acid, focusing attention on the biochemical tests able to study
      therapeutically relevant scavenging properties of various drugs against
      hypochlorous acid itself.

PMID- 8981060
TI  - Interplay between milrinone and adenosine in the inhibition of human platelet
      response.
AB  - 1. In this study, we investigated the influence of the inotropic agent and
      coronary vasodilator milrinone on platelet aggregation and intracellular levels
      of 3',5' cyclic adenosine monophosphate (cAMP) in human platelet-rich plasma
      (PRP) and whole blood (WB). Furthermore, we evaluated the influence of milrinone
      on the effects of adenosine, which reduces the platelet aggregation through an
      elevation of intraplatelet cAMP levels. 2. Milrinone decreased the platelet
      aggregation in response to agonists in both PRP and WB. A dose-dependent increase
      of intraplatelet cAMP levels was demonstrated: this result is in accordance with
      an effect on platelet phosphodiesterases. 3. Milrinone at low concentration and
      adenosine exerted additive effects on platelet aggregation and intraplatelet cAMP
      levels. 4. An interplay between milrinone and adenosine was shown in WB.
      Furthermore, dipyridamole, which prevents the uptake of endogenous adenosine,
      markedly enhanced the milrinone antiaggregating effect, whereas the adenosine
      receptor blocker, theophylline, decreased it. 5. The present data provide
      evidence that milrinone modulates the platelet function through an influence on
      intraplatelet levels of cAMP and it is able to interplay with substances
      stimulating adenylyl cyclase. 6. The interplay between milrinone and adenosine in
      the inhibition of the human platelet function could be effective during milrinone
      administration in the treatment of heart failure, when blood adenosine levels are
      significantly increased. These milrinone effects could be advantageous from a
      therapeutic point of view, since patients with heart failure are at risk of
      thrombosis and ischemic heart disease.

PMID- 8981062
TI  - Effect of the prostacyclin analogue, iloprost, on infarct size after permanent
      focal cerebral ischemia.
AB  - This investigation was undertaken to study the effect of iloprost, a stable
      analogue of prostacyclin, on infarct size after permanent focal cerebral ischemia
      in the rabbit. Forty-two adult rabbits were subjected to left middle cerebral
      artery occlusion via the transorbital route. Fourteen rabbits received an
      intravenous (i.v.) infusion of 30 micrograms/kg iloprost, 7 rabbits received an
      i.v. infusion of 10 micrograms/ kg, and 9 rabbits received an i.v. infusion of 20
      micrograms/kg iloprost. Twelve rabbits received an intravenous infusion of
      saline. Treatment with iloprost started immediately after middle cerebral artery
      occlusion and continued for 1 h. After killing the animals, brains were removed
      and five coronal slices were incubated in a 2,3,5-triphenyltetrazolium chloride
      solution to determine the infarct size. Treatment with 30 micrograms/kg iloprost
      significantly reduced the infarct size compared with treatment with saline (3.49
      +/- 2.79% vs. 9.03 +/- 4.26%, P < 0.001), but the lower doses of iloprost did not
      have a beneficial effect on the size of the infarct. These results suggest that
      intravenous iloprost treatment after occlusion has a highly protective effect
      without any side effects such as hypotension.

PMID- 8981061
TI  - Azirino[1, 2-d][1, 4]benzodiazepine derivatives and related 1,4-benzodiazepines
      as anticonvulsant agents in DBA/2 mice.
AB  - 1. The behavioral and anticonvulsant effects of several 1, 4-benzodiazepine (BDZ)
      and azirino[1,2-d] [1, 4]benzodiazepine (ABDZ) derivatives were studied after
      intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to
      sound-induced seizures. 2. The anticonvulsant effects were evaluated on seizures
      evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed
      singly under a Perspex dome. 3. The 1,4-benzodiazepines were generally more
      potent than the related azirino[1,2-d] [1,4]benzodiazepine derivatives which,
      however, showed a remarkable anticonvulsant activity. The rank order of potency
      for anticonvulsant activity was flunitrazepam > diazepam > pinazepam > ABDZ5 >
      ABDZ4 > prazepam > halazepam > ABDZ1 > ABDZ3 > camazepam > ABDZ6 > ABDZ2. 4. The
      impairment of locomotor performance following intraperitoneal (IP) administration
      of the aforementioned derivatives was also evaluated by means of rotarod test.
      The rank order of potency for impairment of coordinated motor movements was
      pinazepam > flunitrazepam > diazepam > ABDZ5 > prazepam > halazepam > ABDZ4 >
      ABDZ3 > ABDZ1 > camazepam > ABDZ2 = ABDZ6. 5. A hypothermic activity was observed
      after the highest doses of the benzodiazepines studied. 6. The potency of various
      1,4-benzodiazepines and azirino[1, 2-d][1,4]benzodiazepines as inhibitors of
      specific [3H]flumazenil binding to membranes from cerebellum or cortex was
      evaluated. In general, they inhibited [3H]flumazenil binding at the micromolar
      range. However, some ABDZ derivatives, although active as anticonvulsants, failed
      to displace [3H]flumazenil. 7. The azirino[1,2-d] [1,4]benzodiazepine derivatives
      are more lipophilic than the related benzodiazepines, but the different degree of
      anticonvulsant activity and impairment of coordinated motor movements cannot be
      directly related to the lipophilicity of the compounds studied. 8. The
      pharmacologic actions of ABDZ4 and ABDZ5, which appeared as the most potent
      anticonvulsants of the azirino[1,2-d] [1,4]benzodiazepine derivatives, were
      significantly reduced by treatment with flumazenil (8.24 mumol/kg IP) suggesting
      a clear involvement of benzodiazepine mechanisms in the anticonvulsant activity
      of these compounds or their metabolites. 9. The anticonvulsant activity of ABDZ4
      and ABDZ5 was also evaluated against seizures induced by the two beta-carbolines,
      methyl beta-carboline-3-carboxylate (beta-CCM) and methyl6,7-dimethoxy-4-ethyl
      beta-carboline-3-carboxylate (DMCM), in DBA/2 mice. Both ABDZ4 and ABDZ5 gave
      better protection against the seizures induced by beta-CCM than DMCM, suggesting
      a preferential action on BDZ1 receptors.

PMID- 8981064
TI  - Mn(2+)-induced transient contraction of the longitudinal muscle of guinea-pig
      stomach through prostaglandin synthesis.
AB  - 1. A low concentration of Mn2+ (less than 0.3 mM) transiently enhanced a
      contractile force (Mn(2+)-induced TC) of the longitudinal muscles of the guinea
      pig stomach. 2. The Mn(2+)-induced transient contraction (TC) was not blocked by
      TTX (10(-7) M) or atropine (10(-6) M), nor by nifedipine (10(-6) M) or D-600 (10(
      6) M), but was blocked by Ca2+ removal from the Krebs solution. 3. A
      preapplication of indomethacin (10(-7) M) completely inhibited an induction of
      the Mn(2+)-induced TC, but exogenous PGE2 (10(-7) M) was able to induce Mn(2+)
      induced TC even with the presence of indomethacin (10(-7) M) and Mn2+ (0.1 mM) in
      the Krebs solution. 4. Quinacrine (10(-5) M), a phospholipase A2 inhibitor,
      partially inhibited the Mn(2+)-induced TC. 5. These results suggest that Mn(2+)
      induced TC is probably mediated through cyclooxygenase and the subsequent
      generation of prostaglandin leading to the contraction.

PMID- 8981063
TI  - Antinociceptive mechanisms of dipsacus saponin C administered
      intracerebroventricularly in the mouse.
AB  - 1. Dipsacus saponin C (DSC) administered intracerebroventricularly (i.c.v.)
      showed an antinociceptive effect in a dose-dependent (from 3.75 to 30 micrograms)
      manner as measured by the tailflick assay. The antinociception induced by DSC at
      the dose of 30 micrograms was maintained at least 1 h. 2. Sulfated
      cholecystokinin (CCK, from 0.1 to 0.5 ng); muscimol (a GABAA receptor agonist,
      from 50 to 200 ng); MK-801 [(+/-)-5-methyl-10, 11-dihydro-5H-dibenzo (a,d)
      cyclohepten-5, 10-imine maleate, from 0.1 to 1 microgram], a noncompetitive N
      methyl-D-aspartic acid (NMDA) receptor antagonist; or CNQX (6-cyano-7
      nitroquinoxaline-2,3-dione, from 0.1 to 0.5 microgram), a non-NMDA receptor
      antagonist, injected i.c.v. significantly reduced the inhibition of the tail
      flick response induced by DSC (30 micrograms) administered i.c.v. However,
      naloxone (an opioid receptor antagonist, 2 micrograms) or baclofen (a GABAB
      receptor antagonist, 10 ng) did not affect the inhibition of the tail-flick
      response induced by DSC. 3. The intrathecal (i.t.) injection of yohimbine (an
      alpha 2-adrenergic receptor antagonist, from 5 to 20 micrograms) and methysergide
      (a serotonin receptor antagonist, from 5 to 20 micrograms) but not naloxone (from
      2 to 8 micrograms), significantly attenuated inhibition of the tail-flick
      response induced by DSC (30 micrograms) administered i.c.v. 4. Our results
      suggest that DSC has an antinociceptive effect when it is administered
      supraspinally and GABAA, NMDA and non-NMDA receptors, but not opioid and GABAB
      receptors located at the supraspinal level, may be involved in DSC-induced
      antinociception. Furthermore, DSC administered supraspinally may produce
      antinociception by stimulating descending alpha 2-adrenergic and serotonin
      pathways but not the opioidergic pathway.

PMID- 8981065
TI  - Effects of SC-52458, a new nonpeptide angiotensin II receptor antagonist, on
      increase in cytoplasmic Ca2+ concentrations and contraction induced by
      angiotensin II and K(+)-depolarization in guinea-pig taenia coli.
AB  - 1. The effects of angiotensin (Ang) II receptor antagonist, SC-52458, on peak and
      plateau components of Ang II-induced contraction were evaluated in the guinea-pig
      taenia coli. 2. SC-52458 suppressed both the components of and increases in
      cytoplasmic Ca2+ concentrations, [Ca2+]i, coupled with the contraction by Ang II;
      tetrodotoxin and atropine did not affect the contractions. 3. SC-52458 inhibited
      a plateau component of the contraction induced by K(+)-depolarization to some
      extent, without affecting a peak component. 4. SC-52458 suppressed both the
      contraction and increase of [Ca2+]i by antagonizing AT1 receptors in the smooth
      muscle.

PMID- 8981066
TI  - Central effects of opioid agonists and naloxone on blood pressure and heart rate
      in normotensive and hypertensive rats.
AB  - 1. The central cardiovascular effects of several opioid receptor selective
      agonists and the nonselective opioid antagonist, naloxone, were studied in
      anesthetized normotensive control rats, in spontaneously hypertensive rats (SHR),
      and in foot-shock-stressed rats. 2. Receptor-selective agonists injected into the
      rostral ventrolateral medulla (RVLM), paraventricular nucleus (PVN), and dorsal
      hippocampus (dHip) were DAGO (mu), DADLE (delta), and U50,488H (kappa). 3. DAGO
      and DADLE (3 nM) decreased arterial pressure and heart rate in RVLM and PVN of
      all rat strains, while U-50,488H (9 nM) had only minimal effects in these areas.
      4. In dHip, only DADLE (3 nM) had depressor and bradycardic effects, and then,
      only in SHR, with DAGO and U50,488H being ineffective in any strain, even at 9
      nM. 5. Prior injection of naloxone (10 nM) into the RVLM, PVN and dHip blocked
      and postinjection reversed the cardiovascular effects of the agonists. Naloxone
      alone increased blood pressure and heart rate in all three areas, in all rat
      strains except SHR, suggesting a tonic depressor effect of endogenous opioids. 6.
      Lack of significant quantitative differences in opioid agonist and antagonist
      effects between normotensive and hypertensive or stressed rats argues against a
      role for endogenous brain opioids in experimental hypertension.

PMID- 8981067
TI  - Effects of electrical stimulation and morphine microinjection into periaqueductal
      gray on 5-hydroxyindole oxidation current in spinal cord of cats.
AB  - 1. The effects of electrical stimulation and microinjection of morphine into the
      periaqueductal gray (PAG) on the 5-hydroxyindole oxidation current (280-300 mV)
      in laminae I-VI (800-2500 microns) of the spinal cord were examined using in vivo
      voltammetry in anesthetized cats. 2. Electrical stimulation of the PAG (PAG-S)
      both enhanced and attenuated the current. PAG-S increased the signal by 13.3 +/-
      3.7% (laminae I-II: 800-1200 microns) or 19.0 +/- 3.6% (laminae V-VI: 1700-2500
      microns) in comparison to control values. Attenuation by PAG-S decreased the
      signal by 15.3 +/- 2.6% (laminae I-II) or 13.3 +/- 2.0% (laminae V-VI) of control
      values. Naloxone antagonized signal enhancement by PAG-S. 3. Morphine (10
      micrograms/microliter) microinjected into the PAG significantly increased the
      height of the signal (laminae I-II: 15.0 +/- 3.4%, laminae V-VI: 12.2 +/- 1.5%).
      Enhancement by microinjected morphine was antagonized by naloxone. In contrast,
      microinjected morphine also significantly decreased the signal by 10.4 +/- 2.7%
      (laminae I-II) and by 10.3 +/- 1.3% (laminae V-VI) of control values. 4.
      Microinjection of morphine and electrical stimulation of the PAG was observed
      both to enhance and attenuate the oxidation current of 5-hydroxyindole in the
      superficial and deeper dorsal horn. PAG may function to regulate the RVM-spinal
      serotonergic pathway, which modulates the transmission of nociceptive messages at
      the spinal cord.

PMID- 8981068
TI  - Effects of SM-9018, a novel 5-HT2 and D2 receptor antagonist, on electrically
      evoked [3H]acetylcholine release from rat striatal slices.
AB  - 1. Electrical stimulation (1 Hz) of striatal slices evoked Ca(+2)-dependent
      [3H]ACh release, which was inhibited by the D2 agonist quinpirole (QPL). 2. SM
      9018 and other neuroleptics antagonized the QPL-induced inhibition of the evoked
      [3H]ACh release. The relative potencies of the neuroleptics in antagonizing the
      QPL action were nemonapride > haloperidol approximately equal to SM-9018 > >
      chlorpromazine > > SCH 23390, and the rank order, except for nemonapride, was
      consistent with their binding affinities to striatal D2 receptors. 3. SM-9018 was
      weaker than haloperidol in enhancing the [3H]ACh release evoked by higher
      frequency (3 Hz) stimulation, the enhancement being abolished by the depletion of
      endogenous dopamine with reserpine pretreatment. 4. The selective 5-HT2
      antagonist LY 53857 significantly attenuated the stimulatory effects of
      haloperidol on the 3 Hz-evoked [3H]ACh release. 5. These findings suggest that SM
      9018 is as potent as haloperidol in antagonizing the QPL action on [3H]ACh
      release at striatal D2 receptors, but is weaker than haloperidol in enhancing the
      [3H]ACh release under high-frequency stimulation. The 5-HT2 blocking activity of
      SM-9018 seems to be involved in the latter effects.

PMID- 8981069
TI  - Lineweaver-Burk analysis for the blocking effects of mammalian dopamine receptor
      antagonists on dopamine-induced currents in Achatina giant neurones.
AB  - 1. We had demonstrated (Emaduddin et al., 1995) the blocking effects of the three
      mammalian dopamine receptor antagonists, (+/-)-SKF83566 (mammalian dopamine D1
      like receptor antagonist), (+)-UH232 (D2 and D3-like receptor antagonist) and (+/
      )-sulpiride (D2-like receptor antagonist) on the dose (pressure duration)
      response curves of dopamine in the three giant neurone types, LVMN (left visceral
      multiple spike neurone), d-RPeAN (dorsal-right pedal anterior neurone) and v-LCDN
      (ventral-left cerebral distinct neurone), of Achatina fulica Ferussac under
      voltage clamp. In the present study, we analyzed these data by Lineweaver-Burk
      plot. 2. Dopamine-induced inward currents (Iin) of the two neurone types, LVMN
      and d-RPeAN, were blocked by (+/-)-SKF83566 and (+)-UH232 in partly
      noncompetitive and partly uncompetitive manners. (+/-)-Sulpiride had no effect on
      these currents. 3. In contrast, dopamine-induced outward current (Iout) of v-LCDN
      was inhibited competitively by (+/-)-sulpiride and noncompetitively by (+)-UH232.
      (+/-)-SKF83566 had no effect on this current. 4. Therefore, we consider that the
      pharmacological features of the dopamine receptors of Achatina neurones are not
      identical in detail to those of the mammalian dopamine receptors.

PMID- 8981070
TI  - The therapeutic effect of a combination of cofpropamine, a caffeine derivative,
      and cyclophosphamide on the development of adjuvant arthritis of rats and
      collagen arthritis of mice.
AB  - 1. Cofpropamine (Cofa), a caffeine derivative that inhibits
      polyadenoribosylation, enhances the therapeutic effect of cyclophosphamide (CPA)
      in two animal models of arthritis. 2. The development of adjuvant arthritis of
      rats is reduced by treatment with 2 x 50 mg/kg IP CPA and 2 x 50 mg/kg IP Cofa.
      3. The development of collagen arthritis in mice is prevented by treatment with
      12.5 mg/kg IP CPA and 150 mg/kg IP Cofa three times per week.

PMID- 8981071
TI  - Insulin reversibility of the isoproterenol resistance of diabetic rat myocardium.
AB  - 1. Efficiency of preventive and reversive insulin therapy was compared on rat
      myocardium following streptozotocin treatment to study the reversibility of
      diabetic catecholamine resistance. 2. When insulin substitution was initiated
      immediately after streptozotocin treatment, insulin successfully prevented the
      development of diabetic catecholamine resistance of the myocardium. 3. When
      insulin substitution was initiated following the development of isoproterenol
      resistance, insulin failed to restore physiological catecholamine sensitivity. 4.
      These results indicate that once diabetic alterations have already developed,
      recovery of biological functions to normal by exogenous insulin substitution
      might be ineffective.

PMID- 8981072
TI  - Effect of the milk extract of Semecarpus anacardium nut on adjuvant arthritis--a
      dose-dependent study in Wistar albino rats.
AB  - 1. Adjuvant-induced arthritis in rats is used as a pathologic model for chronic
      inflammatory disease to evaluate the efficacy of therapeutic agents. 2. In the
      present work, attempts have been made to study the potency of a milk extract of
      Semecarpus anacardium (Serankottai Nei), a Siddha preparation from Semecarpus
      anacardium nut, which has been shown to have antiarthritic effects. 3.
      Experimental arthritis induces a significant modification in lysosomal enzyme
      release and total carbohydrate components of glycoprotein. 4. Milk extract was
      administered at the dose level of 50, 100, 150, 200, and 250 mg/kg body weight in
      olive oil orally (volume 0.5 ml) after 14 days from the day of adjuvant
      injection. 5. After administration of the extract the lysosomal enzyme activity
      and protein-bound carbohydrate component levels were significantly normalized. 6.
      The data obtained clearly indicate that the Semecarpus anacardium is effective at
      the dose level of 150 mg/kg body weight in adjuvant-induced arthritis in albino
      Wistar rats.

PMID- 8981073
TI  - Cardiac mechanical and electrophysiologic modulations of guinea-pig by caffeine
      and thapsigargin.
AB  - 1. The effects of caffeine and thapsigargin on the contractile force and the
      action potential in guinea-pig papillary muscles were examined. 2. Caffeine (1 to
      10 mM) initially increased contractile force in a concentration-dependent manner.
      Subsequently, 1 mM caffeine decreased it as compared with precaffeine level (but
      not significantly). At 5 mM or 10 mM, caffeine also decreased contractile force,
      but the decrease was still positive as compared with control level. 3. Exchange
      to low [Ca]o (0.9 mM) or high [K]o (8 mM) decreased steady-state value during
      exposure to 1 mM caffeine. Addition of 1 microM thapsigargin (TG) decreased the
      steady-state value during exposure to 1 mM caffeine, but enhanced it with 5 mM
      and 10 mM caffeine. TG (1 microM) alone increased the force. 4. In
      electrophysiologic, studies, caffeine shortened the action potential duration
      (APD) in a concentration-dependent manner. In the presence of caffeine (1 mM),
      high [K]o shortened APD and decreased the action potential amplitude and resting
      potential. 5. These results suggest that in the presence of caffeine and/or
      thapsigargin calcium overload might not occur in the left ventricular papillary
      muscles of the guinea-pig heart.

PMID- 8981074
TI  - Examination of coumarins, flavonoids and polysaccharopeptide for antibacterial
      activity.
AB  - 1. Coumarins, flavonoids and polysaccharopeptide were tested for antibacterial
      activity. 2. The bacteria used for this study included clinical isolates of
      Staphylococcus aureus, Shigella flexneri, Salmonella typhi, Escherichia coli and
      Pseudomonas aeruginosa. 3. Most of the coumarins tested failed to inhibit the
      bacteria at 25 mg/l. Edultin at 128 mg/l inhibited 4 of the 8 P. aeruginosa
      strains and 1 of the S. aureus strains tested. O-acetylcolumbianetin and
      imperatorin did not inhibit any isolate, even at 128 mg/l. 4. When tested at the
      dose of 128 mg/l, the flavonoids (rutin, naringin and baicalin) inhibited 25% or
      less of P. aeruginosa and only baicalin was active against S. aureus. 5. Arbutin
      and 4-(beta-D-glucopyranosyloxyl)-benzaldehyde inhibited 3 of the 8 P. aeruginosa
      strains when tested at 128 mg/l. 6. Polysaccharopeptide from the fungus Coriolus
      versicolor failed to inhibit any P. aeruginosa or S. aureus strain at 128 mg/l.

PMID- 8981075
TI  - Effects of carbamylcholine and pyridostigmine on cytoskeleton-bound and cytosolic
      phosphofructokinase and ATP levels in different rat tissues.
AB  - 1. The effects of carbamylcholine (CaCh) (acetylcholine agonist) and
      pyridostigmine (Pyr) (acetylcholinesterase inhibitor), on the activity of
      cytoskeleton-bound and cytosolic phosphofructokinase (PFK), the rate-limiting
      enzyme in glycolysis, and ATP levels, were studied in rat tibialis anterior (TA)
      muscle, heart, and brain. 2. In the TA muscle, a marked (about three-fold)
      increase in the allosteric activity of cytosolic (soluble) PFK was found, 3-5 min
      following the injection of CaCh or Pyr. The intracellular distribution of the
      enzyme was not affected by both drugs. Stimulation of glycolysis in this muscle
      was also expressed by a significant increase in the concentrations of glycolytic
      intermediates and lactate. Glucose 1,6-bisphosphate (Glc-1,6-P2) levels were
      unchanged, whereas fructose-2,6-bisphosphate (Fru-2,6-P2) was increased.
      Glycogenolysis was also stimulated, as deduced from the decrease in glycogen
      content. The stimulation of glycolysis, induced by both drugs, was accompanied by
      an increase in ATP level in the TA muscle. 3. In contrast to the stimulatory
      action of CaCh or Pyr on glycolysis in the TA muscle, both drugs had no effect on
      cytosolic and cytoskeletal PFK in heart and brain. However, ATP content in both
      heart and brain was markedly reduced by these drugs, most probably due to their
      reported harmful effects on mitochondrial function, leading to tissue damage. 4.
      Electron microscopic studies of TA muscle and heart from rats treated with CaCh
      or Pyr, revealed severe damage of heart but no harmful effects on TA muscle,
      which is a muscle with high glycolytic and low oxidative capacity. The present
      experiments suggest that the accelerated glycolysis in this muscle induced by
      both drugs, supplies ATP, thus preventing muscle damage.

PMID- 8981076
TI  - Electrical and mechanical characteristics of the atrium of the whelk Busycon
      canaliculatum.
AB  - 1. The mean resting potential of 22 atrial preparations of Busycon heart was 42.5
      mV, examined by the sucrose gap technique. Spontaneous action potentials of 8-18
      mV amplitude occurred in repeated cycles of burst activity, generating burst
      patterned phasic contractile activity. 2. Isolated ventricles showed slow (1-3
      beats min-1) constant myogenic contractile activity, suggesting that the primary
      driving pacemaker may reside in the atrium. 3. The atrial electrocardiogram
      commenced with a small prepotential leading to a plateau-like phase and
      terminated with a sharp spike potential. 4. Acetylcholine (ACh) at high
      concentrations depolarised the atrium by 5-8 mV and induced strong tonic
      contractures while suppressing spontaneous action potentials, suggesting an
      overall inhibitory role in downregulating cardiac intrinsic myogenic rhythms. 5.
      Serotonin (5-hydroxytryptamine, 5HT) was consistently excitatory, enhancing both
      action potential amplitude and rhythmic contractions by up to 50% at
      concentrations of 5 x 10(-7) to 10(-5)M. Neither methysergide nor metoclopramide
      affected atrial responses to 5HT and the 5HT1 antagonist metitipine simply
      increased action potential discharge in the rhythmic cycle. The vertebrate 5HT1-3
      receptor classification is inappropriate to this molluscan preparation. 6. The
      atrium was very sensitive to the tetrapeptides FMRF- and FLRFamide, but the
      enhanced phasic contractions were not accompanied by alteration of resting
      potential or action potential amplitude, suggestive of neuromodulatory
      upregulation involving a secondary messenger. The related peptide SCP-B was
      without effect on the preparation, but GAPFLRFamide was excitatory, although much
      less so than FMRF- and FLRFamide. 7. Neither adenosine and ATP nor guanosine and
      GTP affected intrinsic atrial electrical or mechanical activity, suggesting that
      there was no noncholinergic, nonaminergic element to cardiac neuromodulation in
      this species. Only ACh, 5HT and FMRF/FLRFamide could be assigned clear roles in
      this respect.

PMID- 8981077
TI  - Pharmacological activity of the new calcium antagonist, lacidipine, on isolated
      preparations.
AB  - 1. The calcium-channel blocking activity of lacidipine has been studied compared
      with that of nifedipine and verapamil on the isolated rabbit heart and aorta. 2.
      All the compounds induced a dose-dependent negative inotropic effect (10(-8)-10(
      5) M); although lacidipine showed less, but longer lasting, activity. 3.
      Lacidipine showed a weak negative chronotropic effect and nifedipine was
      ineffective. Only verapamil strongly decreased the heart rate. 4. The three
      calcium antagonists abolished vasopressin-induced coronary spasm and inhibited
      partially metoxamine-induced coronary spasm. Only lacidipine reduced basal
      coronary pressure. 5. In the aortic strips, all the compounds antagonized KCl
      induced contractions, and they exerted a partial effect on noradrenaline- and
      angiotensin II-induced contractions.

PMID- 8981078
TI  - Some pharmacologic and toxicologic studies on Rhazya stricta decne in rats, mice
      and rabbits.
AB  - 1. This work examines some in vivo and in vitro pharmacologic and toxicologic
      effects of extracts of Rhazya stricta, a medicinal plant in the United Arab
      Emirates. 2. R. stricta extracts at doses of 0.1-10 mg reduced the mean arterial
      blood pressure (MBP) of anesthetized rats in a dose-dependent manner. The
      depressor effect was partially sensitive to atropine (5 microM). Although the MBP
      was reduced by 50% by both doses of extracts, the normal electrocardiogram
      pattern and the heart rate remained unaltered. 3. Acute treatment of rats with
      the lyophilized extract at doses of 4 g/kg produced a significant rise in insulin
      concentration. In streptozotocin-diabetic rats loaded orally with glucose (1
      g/kg), R. stricta at doses of 8 g/kg produced significant decreases in plasma
      glucose concentration at 0.5 and 1 h after treatment. 4. Chronic treatment of
      rats and mice for 28 days with the lyophilized extract of R. stricta did not
      affect the plasma glucose or insulin concentration or any of the hematological or
      biochemical indices measured. 5. The extracts of R. stricta (0.5-4 g/kg) dose
      dependently decreased the gastrointestinal transit time in mice by 4-50%. 6. The
      butanolic extract of R. stricta (1 and 2 g/kg) significantly reduced the
      carrageenan-induced increase in raw paw edema 3 and 4 h after the extract
      administration. 7. The rectal temperatures of normothermic and pyrexic rats were
      reduced significantly 0.5 and 1 h after administration of butanolic R. stricta at
      doses of 1 and 2 g/kg. 8. The butanolic extract of R. stricta at doses of 1 and 2
      g/kg significantly increased the reaction time on the hot plate 30 and 60 min
      after administration to rats. 9. At concentration < 0.05 mg/ml (bath
      concentration), lyophilized water and butanol extracts of R. stricta potentiated
      the twitch responses induced by indirect electrical stimulation in the rat
      phrenic nerve diaphragm preparation. The responses were inhibited by
      concentrations > 0.05 mg/ml. Neostigmine (2 x 10(-4)M) did not alter these
      effects of the extracts. 10. R. stricta extracts dose-dependently decreased the
      force of contraction and heart rate of the isolated rabbit heart. Atropine (1 x
      10(-5)M) had no effect on the inhibitory activity of these extracts. The
      lyophilized water extract (> 10 mg) and butanol extract (> 5 mg) produced
      irreversible inhibition and disturbances in the force of contraction and heart
      rate.

PMID- 8981079
TI  - Baclofen: intestinal absorption mechanism in mice.
AB  - 1. The duodenal transfer of baclofen from sacs of mouse intestine was determined.
      2. A linear relationship between the steady-state transfer rate of total and the
      initial mucosal baclofen concentration was observed, suggesting that the
      clearance is the same at different concentrations. 3. There was no significant
      difference in the amount of total drug removed between control and everted
      tissues. 4. The data support the idea that the principal transfer mechanism for
      baclofen is simple diffusion in mouse intestine.

PMID- 8981080
TI  - Are imidazoline receptors involved in sympathetic neurotransmission in rat vas
      deferens?
AB  - 1. An involvement of imidazoline receptors in the modulation of neurotransmitter
      release was investigated in the prostatic portion of the rat vas deferens
      stimulated transmurally at 0.2 Hz or by single pulses. 2. Idaxozan and yohimbine
      induced a concentration-dependent potentiation of the contractile response to 0.2
      Hz transmural stimulation in the epididymal and prostatic portion of the vas. 3.
      After reserpine treatment, idazoxan, but not yohimbine, still potentiated the
      contractile response, suggesting a possible involvement of imidazoline receptors.
      4. Clonidine and rilmenidine, agonists with different affinities to alpha 2
      adrenoceptors and imidazoline receptors, inhibited with the same potency the
      contractile responses to a single pulse transmural stimulation. 5. Yohimbine (a
      selective alpha 2-adrenoceptor antagonist) antagonized the inhibitory
      concentration effect curve to rilmenidine in a competitive manner. pA2 values for
      idaxozan (an antagonist to alpha 2-adrenoceptors and imidazoline receptors) were
      not different when noradrenaline or rilmenidine were used as agonists.
      Phenoxybenzamine blocked the effect of both agonists. 6. Thus, the potency
      relationship of agonists, as well as the effect of the antagonists, did not favor
      the hypothesis that imidazoline receptors are involved in the idazoxan
      potentiating effect in the rat vas deferens.

PMID- 8981081
TI  - Organization of glycosaminoglycan sulfation in the biosynthesis of
      proteochondroitin sulfate and proteodermatan sulfate.
AB  - Although the intermediates for sulfation of proteochondroitin and proteodermatan
      have been known for several decades, organizational aspects of this formation
      have not been clearly defined. Work in several laboratories, including our own,
      have indicated a pattern which strongly suggests that sulfation ordinarily takes
      place together with glycosaminoglycan polymerization in the same Golgi sites, and
      with close relationship to aspects of polymer elongation, polymer modification
      and polymer termination. The organization of sulfation together with
      polymerization may be a major factor controlling the location, type, and degree
      of sulfation, which in turn may direct specific functions of these proteoglycans.

PMID- 8981083
TI  - A 1H NMR investigation of the hydrolysis of a synthetic substrate by KDN
      sialidase from Crassostrea virginica.
AB  - The mechanism of hydrolysis of 4-methylumbelliferyl 3-deoxy-D-glycero-alpha-D
      galacto-2-nonulopyranosidonic acid (KDN alpha 2MeUmb, 4) by KDN-sialidase
      isolated from the hepatopancreas of the oyster Crassostrea virginica has been
      monitored by 1H NMR spectroscopy. The results of these experiments reveal that
      KDN-sialidase catalyses the hydrolysis of the synthetic substrate KDN alpha
      2MeUmb, with initial release of alpha-D-KDN. This is consistent with an overall
      mechanism for the hydrolysis which proceeds with retention of anomeric
      configuration. These results agree with earlier NMR studies of other N
      acetylneuraminic acid-recognising sialidases from both viral and bacterial
      sources.

PMID- 8981084
TI  - Synthesis of a novel glycosaminoglycan pentasaccharide serine having an N
      acetylgalactosamine residue alpha-linked to the core linkage tetrasaccharide.
AB  - A novel pentaosyl serine; GalNAcalpha(1--4)GlcAbeta(1--3)Galbeta(1--3)Galbeta  (1
      -4)Xylbeta(1--3)Ser (2), a putative intermediate of chondroitin sulfate and/or
      heparan sulfate biosynthesis, was synthesized.

PMID- 8981082
TI  - The Sialoadhesins--a family of sialic acid-dependent cellular recognition
      molecules within the immunoglobulin superfamily.
AB  - For many years evidence has accumulated that sialic acids function in cellular
      interactions either by masking or as a recognition site. However, receptors or
      adhesion molecules mediating such functions between eukaryotic cells were unknown
      until about 5 years ago, when it was found that the members of the Selectin
      family mediate adhesion of leukocytes to specific endothelia through binding to
      sialylated glycans like sialyl Lewis. More recently, the Sialoadhesin family of
      sialic acid-dependent adhesion molecules was defined within the superfamily of
      immunoglobulin-like molecules. So far, it has been shown that sialoadhesin (Sn),
      CD22, CD33, the myelin-associated glycoprotein (MAG) and the Schwann cell myelin
      protein (SMP) belong to this family. In contrast to the Selectins, these proteins
      are associated with diverse biological processes, i.e. hemopoiesis, neuronal
      development and immunity. In this review their properties, carbohydrate
      specificities and potential biological functions are discussed. Finally, we
      provide perspectives with respect to the nature of ligands, implications of
      sialic acid modifications and future research.

PMID- 8981085
TI  - Involvement of sphingolipids metabolites in cellular proliferation modulated by
      ganglioside GM1.
AB  - The B subunit of cholera toxin, which binds specifically to ganglioside GM1, is
      mitogenic for quiescent Swiss 3T3 fibroblasts. Recently, sphingolipids
      metabolites, ceramide, sphingosine and sphingosine-1-phosphate, have been
      implicated as second messengers in cell growth regulation and differentiation. In
      this paper, we examined the possibility that interaction of the B subunit with
      membrane GM1 leads to alterations in metabolism of glycosphingolipids and that
      increased levels of sphingolipids metabolites may mediate the biological effects
      of the B subunit. While the B subunit did not induce a change in the level of
      ceramide or sphingosine, the level of sphingosine-1-phosphate was rapidly and
      transiently increased. The B subunit also transiently activated cytosolic
      sphingosine kinase activity, which catalyzes the phosphorylation of the primary
      hydroxyl group of sphingosine to produce sphingosine-1-phosphate. To determine
      whether the increase in sphingosine-1-phosphate level plays a role in B subunit
      induced mitogenicity, we used a competitive inhibitor of sphingosine kinase, D,L
      threo-dihydrosphingosine. D,L-thereo-Dihydrosphingosine not only inhibited B
      subunit-induced DNA synthesis by 26%, it also reduced its ability to stimulate
      DNA-binding activity of the transcription factor AP-1. This sphingosine kinase
      inhibitor also inhibited B subunit-induced increases in the activity of cell
      cycle-regulated, cyclin-dependent serine/threonine kinases, cdk2 and p34cdc2.
      These findings suggest that sphingosine-1-phosphate may play a role in the signal
      transduction pathways activated by binding of the B subunit to endogenous
      ganglioside GM1.

PMID- 8981086
TI  - Simultaneous expression by porcine aorta endothelial cells of glycosphingolipids
      bearing the major epitope for human xenoreactive antibodies (Gal alpha 1-3Gal),
      blood group H determinant and N-glycolylneuraminic acid.
AB  - Glycosphingolipids were isolated from primary cultures of porcine endothelial
      cells labelled with 14C-galactose or 14C-glucosamine. They were characterized by
      their mobility on thin layer chromatogram, their sensitivity to exoglycosidases,
      and their labelling with antibodies. In addition to the major glycosphingolipids,
      globotetra- and globotriaosylceramide, minor ones were identified as penta- and
      heptaglycosylceramide of the neolactoseries terminated by either Gal alpha 1-3Gal
      (xenoreactive epitope) or Fuc alpha 1-2Gal- (H determinant). Two gangliosides
      were found, GM3 and GD3, and N-glycolylneuraminic acid was their major sialic
      acid. Therefore, porcine endothelial cells differ from human endothelial cells by
      expression of glycosphingolipids that are absent in man: two Gal alpha 1-3Gal
      terminated glycolipids recognized by human natural antibodies, and two N
      glycolylneuraminic acid-terminated gangliosides which are potent immunogens.

PMID- 8981087
TI  - Structural variation in the glycoinositolphospholipids of different strains of
      Trypanosoma cruzi.
AB  - The structures of the glycoinositolphospholipids (GIPLs) from five strains of the
      protozoan parasite Trypanosoma cruzi have been determined. Two series of
      structures were identified, all but one containing the same Man4(AEP)GlcN-Ins-PO4
      core. Series 1 oligosaccharides are substituted at the third mannose distal to
      inositol (Man 3) by ethanolamine-phosphate or 2-aminoethylphosphonic acid, as are
      some glycosyl-phosphatidylinositol-protein anchors of T. cruzi. The core can be
      further substituted by terminal (1-3)-linked beta-galactofuranose units. In
      contrast, Series 2 oligosaccharides do not have additional phosphorus-containing
      groups attached to Man 3, the latter being substituted instead by a single side
      chain unit of beta-galactofuranose. Series 1 oligosaccharides are present in all
      strains (G, G-645, Tulahuen CL, and Y) whereas Series 2 structures are present
      mainly in CL and Y strains. The lipid moiety in the GIPLs from the G, G-645 and
      Tulahuen strains is predominantly ceramide, as reported for the Y strain, whilst
      that from the CL strain is a mixture of ceramide and alkylacylglycerol species.
      The lipid moiety of the GIPLs, and probably also the phosphoinositol
      oligosaccharide structures may play an important immunomodulatory role in
      infection by T. cruzi.

PMID- 8981089
TI  - Primary structure of the N-linked carbohydrate chains of Calreticulin from
      spinach leaves.
AB  - Calreticulin is a multifunctional Ca(2+)-binding protein of the endoplasmic
      reticulum of most eukaryotic cells. The 56 kDa Calreticulin glycoprotein isolated
      from spinach (Spinacia oleracea L.) leaves was N-deglycosylated by PNGase-F
      digestion. The carbohydrate moiety was isolated by gel permeation chromatography
      and purified by high-pH anion-exchange chromatography. The fractions were
      investigated by 500 MHz 1H-NMR spectroscopy, in combination with monosaccharide
      analysis and fast-atom bombardment-mass spectrometry. The following carbohydrate
      structure could be established as the major component (Man8GlcNAc2): (sequence
      see text) Heterogeneity was demonstrated by the presence of two minor components
      being Man7GlcNAc2 lacking a terminal residue (D1 or D3), compared to the major
      component. A cross-reactivity with an antibody against the endoplasmic reticulum
      retention signal HDEL was also found.

PMID- 8981088
TI  - A sialic acid-binding lectin from ovine placenta: purification, specificity and
      interaction with actin.
AB  - A sialic-acid-specific lectin from ovine placental cotyledons was purified by
      affinity chromatography on bovine submaxillary mucin-agarose followed by gel
      filtration, and it showed a molecular weight of 65000 by sodium dodecylsulfate
      polyacrylamide gel electrophoresis. This lectin has the capacity to interact with
      actin, since it binds to actin-F in a cosedimentation assay and it acts as a
      mediator in the binding of actin to the affinity column. The lectin agglutinated
      rabbit and rat erythrocytes, but not human A, B or O erythrocytes.
      Haemagglutination inhibition assays of different saccharides, glycoproteins and
      glycolipids indicate that this lectin has affinity for sialic acid, which is
      enhanced by its O-acetylation. The N-terminal sequence of the protein shows 92%
      identity with rabbit and porcine uterine calreticulin.

PMID- 8981091
TI  - Synthesis of the disaccharides methyl 4-O-(2'/3'-O-sulfo-beta-D
      glucopyranosyluronic acid)-2-amino-2-deoxy-alpha-D-glucopyranoside disodium
      salts, related to heparin biosynthesis.
AB  - The synthesis of the disaccharides methyl 4-O-(2'/3'-O-sulfo-beta-D
      glucopyranosyluronic acid)-2-amino-2-deoxy-alpha-D-glucopyranoside 3 and 4 as
      disodium salts is described. Allyl 4,6-O-benzylidene-alpha-D-glucopyranoside 6
      was converted to trichloroacetimidate 20. Glycosylation of 20 with 5 promoted by
      BF3.OEt2 gave disaccharide 21. Deacetylation of 21 followed by monoacetylation of
      the resultant diol 22 afforded the two monoacetylated disaccharides 23 and 24.
      Sulfation and deprotection of each disaccharide gave the desired sulfated
      compounds 3 and 4.

PMID- 8981090
TI  - Molecular basis for erythrocyte Le(a+ b+) and salivary ABH partial-secretor
      phenotypes: expression of a FUT2 secretor allele with an A-->T mutation at
      nucleotide 385 correlates with reduced alpha(1,2) fucosyltransferase activity.
AB  - The SewA385T mutation of the FUT2 gene was found to correlate with both the
      erthrocyte Le(a + b+) and/or salivary ABH partial-secretor phenotypes of
      Polynesians. Constructs with FUT1 and FUT2 wild type genes, and the FUT2
      SewA385T, seG428A and seC571T mutated alleles, were cloned into pcDNAI, and
      expressed in COS-7 cells. COS-7 cells transfected with the SewA385T allele had
      weak, but detectable, alpha(1,2)fucosyltransferase activity, with an acceptor
      substrate pattern similar to the wild type FUT2 gene. Comparative kinetic studies
      from cell extracts with mutated SewA385T and wild type FUT2 alleles gave similar
      Km values, but less enzyme activity was present in cells transfected with
      SewA385T (Vmax 230 pmol h-1 mg-1), as compared to those transfected with FUT2
      (Vmax 1030 pmol h-1 mg-1), suggesting that the mutated enzyme is more unstable.
      These results confirm that the molecular basis for the erythrocyte Le(a + b+),
      and the associated ABH salivary partial-secretor phenotype, is an amino acid
      change of Ile129-->Phe in the secretor alpha(1,2)fucosyltransferase.

PMID- 8981092
TI  - Adhesion of Helicobacter pylori strains to alpha-2,3-linked sialic acids.
AB  - Helicobacter pylori is a human pathogen associated with gastritis and peptic
      ulcer. Adhesion properties of H. pylori to various structures have been described
      in the literature, including evidence for sialic acid-binding. To study the
      specificity and frequency of sialic acid-binding, fourteen H. pylori strains were
      investigated using haemagglutination with derivatized erythrocytes carrying
      sialic acids only on defined glycans and using haemagglutination inhibition
      assays. From these studies H. pylori strains can be grouped into sialic acid
      dependent and sialic acid-independent classes. The sialic acid-dependent strains
      require alpha-2,3-linked sialic acid for haemagglutination. The potential roles
      of sialic acid-dependent adhesions for H. pylori-related infections are
      discussed.

PMID- 8981093
TI  - Biological and physicochemical characterization of recombinant human
      erythropoietins fractionated by Mono Q column chromatography and their
      modification with sialyltransferase.
AB  - Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from
      9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived
      recombinant human EPO by Mono Q column chromatography. The mean pI values of the
      EPO fractions determined by IEF-gel electrophoresis systematically shifted from
      4.11 to 3.31, coinciding with the sialic acid content, without a change in the
      constitution of asialo N-linked oligosaccharides of each fraction. Although a
      linear relationship between the in vivo bioactivity and the sialic acid content
      of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was
      no further increase in their activity over 12.4 mol mol-1 of EPO. On the other
      hand, an inverse relationship between the in vitro bioactivity and sialic acid
      content of EPO was observed. Also, we showed that the in vivo bioactivity of some
      fractions with low sialic acid contents was increased after treatment with alpha
      2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with
      high sialic acid contents was either decreased or not affected.

PMID- 8981094
TI  - Elevation of an alpha(1,3)fucosyltransferase activity correlated with apoptosis
      in the human colon adenocarcinoma cell line, HT-29.
AB  - We studied changes in the carbohydrate expression following apoptotic cell death
      induced by treatment with interferon (IFN)-gamma and anti-Fas antibody using
      human colon adenocarcinoma HT-29 cells. An apoptotic cell death of HT-29
      accompanied with typical DNA fragmentation was observed when the cells, were
      cultured sequentially with IFN-gamma and anti-Fas antibody. In flow cytometric
      analyses, the expression of Le(x) and Le(y) antigen was strongly and slightly
      enhanced, respectively, on the cell surface in accordance with the apoptosis.
      When the fucosyltransferase (Fuc-T) activities of the lysates from the treated
      cells were examined relative to those from untreated cells, a 2.5-fold increase
      of alpha(1,3)-Fuc-T activities and a slight increase of alpha(1,2)-Fuc-T
      activities were observed, but little or no increase of alpha(1,4)-Fuc-T activity
      was detected. In Northern blot analyses using probes for Fuc-T III, IV, V, VI and
      VII genes, strong RNA messages for Fuc-T III, V and/or VI and a weak RNA message
      for Fuc-T IV were detected in the untreated HT-29 cells. On the other hand, in
      the treated cells, the messages for Fuc-T III, V and/or VI were found to almost
      disappear and the 2.3 kb message for Fuc-T IV was observed to elevate 2.8-fold.
      Therefore, we suggest that the strongly increased expression of Le(x) antigen
      found on the HT-29 cell surface might be involved in the process of apoptosis,
      and that the enhancement of the antigen expression seems to result from the
      increased activity of alpha(1,3)-Fuc-T encoded mainly by the Fuc-T IV gene.

PMID- 8981097
TI  - Immunotoxicity: hazard identification and risk assessment.

PMID- 8981096
TI  - An improved ELISA for the determination of sialyl Lewis(x) structures on purified
      glycoconjugates.
AB  - The membrane carbohydrate antigen, sialyl Lewis x (sLe(x)), is involved in
      cellular adhesive interactions in many diseases, such as cancer, inflammation and
      thrombosis. This antigen is also found on soluble macromolecules, such as serum
      glycoproteins, but the precise role of soluble sLe(x) in modifying disease
      processes, or reflecting the pathological changes is still unclear. Although
      methods were previously reported for the measurement of soluble sLe(x), many of
      these were not well characterised, measurements were mainly made on mixtures of
      molecules, and the anti-sLe(x) antibodies were used at concentrations that made
      the assay expensive. In this study an ELISA has been devised that detects sLe(x)
      in purified soluble glycoconjugates using the anti-sLe(x) antibody, CSLEX I.
      Commercially-available haptoglobin (Hp) and synthetic complexes of Lewis antigens
      with polyacrylamide were used as model substances in developing the procedure.
      Key steps were washing the antibody/antigen complex with ten times diluted salt
      solution to prevent dissociation of the complex and the use of bovine serum
      albumin for blocking non-specific interactions. The assay was shown to be very
      specific, its precision was in the range 6-12%, and it could detect less than a
      pmol of sLe(x). It could also distinguish between different densities of sLe(x)
      on the same amount of glycoconjugate. Determination of sLe(x) in Hp isolated from
      small groups of healthy individuals, cancer patients, and rheumatoid arthritis
      sufferers suggested that the antigen expression is increased in disease. This
      method, which is an improvement on those previously described will be useful for
      determining sLe(x) in many different types of soluble glycoconjugate, and used in
      combination with synthetic carbohydrate polyacrylamide complexes, will help to
      standardize measurements of soluble sLe(x) in the future.

PMID- 8981095
TI  - The identification of abnormal glycoforms of serum transferrin in carbohydrate
      deficient glycoprotein syndrome type I by capillary zone electrophoresis.
AB  - One of the biochemical characteristics of carbohydrate deficient glycoprotein
      syndromes is the presence of abnormal glycoforms in serum transferrin. Both
      glycoform heterogeneity and variable site occupancy may, in principle, lead to
      the generation of a range of glycoforms which contain different numbers of sialic
      acid residues, and therefore variable amounts of negative charge. Capillary zone
      electrophoresis was used to resolve the glycoforms of normal human serum
      transferrin and also of a set of glycoforms which were prepared by digesting the
      sugars on the intact glycoprotein with sialidase. The sugars on the intact
      glycoprotein were also modified by a series of exoglycosidase enzymes to produce
      a series of neutral glycoforms which were-also analysed by capillary zone
      electrophoresis. The oligosaccharide population of human serum transferrin was
      analysed by a series of mixed exoglycosidase digests on the released glycan pool
      and quantified using a novel HPLC strategy. Transferrin was isolated from
      carbohydrate deficient glycoprotein syndromes type I serum and both the intact
      glycoforms and released sugars were resolved and quantified. The data presented
      here confirm the presence of a hexa-, penta- and tetra-sialoforms of human serum
      transferrin in both normal and carbohydrate deficient glycoprotein syndrome type
      I serum samples. Consistent with previous reports carbohydrate deficient
      glycoprotein syndrome type I transferrin also contained a di-sialoform,
      representing a glycoform in which one of the two N-glycosylation sites is
      unoccupied, and a non-glycosylated form where both remain unoccupied. This study
      demonstrates that capillary zone electrophoresis can be used to resolve
      quantitatively both sialylated and neutral complex type glycoforms, suggesting a
      rapid diagnostic test for the carbohydrate deficient glycoprotein syndromes group
      of diseases.

PMID- 8981098
TI  - Characterisation and uptake of paraquat by rat renal proximal tubular cells in
      primary culture.
AB  - 1 Uptake of the herbicide paraquat (PQ), by rat proximal tubular cells (PTC) in
      primary culture grown on a collagen coated support was investigated. 2 The uptake
      of PQ by PTC was predominantly from the basolateral side. The basolateral uptake
      of PQ was saturable with time and increasing concentrations, energy dependent and
      could be inhibited by certain organic cations. Using Michaelis Menten kinetics,
      the apparent K(m) was 778 +/- 241 microM and Vmax was 0.97 +/- 0.24
      pmol/microgram protein/15 min for the basolateral uptake of PQ. Cimetidine (5.7
      +/- 0.4 pg/microgram protein/ 30 min, P < 0.001) was the most potent inhibitor of
      PQ uptake, followed by quinine (6.5 +/- 0.4 pg/microgram protein/30 min, P <
      0.01) and then tetraethylammonium (8.2 +/- 0.5 pg/microgram protein/30 min, P <
      0.05) when compared with control (11 +/- 1 pg/microgram protein/30 min). N
      methylnicotinamide, p-aminohippurate and putrescine did not inhibit the
      basolateral uptake of PQ. The sodium hydrogen exchange inhibitors, amiloride and
      its analogue, 5-(N,N hexamethylene) amiloride (HMA) inhibited both the apical and
      basolateral uptake of PQ. 3 The apical uptake of PQ was not saturable with
      increasing concentrations and was not inhibited by 2,4-dinitrophenol, but it was
      reduced by cimetidine (P < 0.01), quinine (P < 0.05) and a sodium potassium
      ATPase inhibitor, ouabain (P < 0.01). 4 It is concluded that PQ was taken up from
      the basolateral side of primary cultured rat PTC by an energy dependent transport
      system.

PMID- 8981099
TI  - Clinical and biochemical changes in greenhouse sprayers chronically exposed to
      pesticides.
AB  - 1 This study was conducted with the aim of evaluating the impact on health
      produced by the use of different types of pesticides in greenhouses. It is based
      on the need to practice and develop biological monitoring techniques to assess
      exposure and predict health risk in workers occupationally exposed to pesticides.
      2 Two groups of greenhouse workers with either high or low exposure to a
      combination of pesticides was taken in Almeria, a Spanish province where cultures
      under plastic are very extended. 3 One hundred and five sprayers were interviewed
      to collect information about symptoms and signs related to past exposures. Each
      pesticide sprayer was examined by a physician, and a blood sample was drawn for
      plasma and red blood cell cholinesterases, complete blood count, and liver and
      renal function tests. 4 Exposure of workers to a combination of pesticides
      resulted in 37% of the workers showing toxic signs and symptoms. The main toxic
      effect observed were a high incidence of spontaneous abortion, depression, and
      certain neurologic disorders like headache, tremor and paraesthesia. 5 The major
      analytical change was a decrease of the mean corpuscular haemoglobin
      concentration in 38% of the cases. However, no significant decrease in both serum
      and erythrocyte cholinesterase activities was observed. 6 The sprayers were not
      usually aware of the potential hazards of pesticides and did not try their best
      to maintain personal hygiene.

PMID- 8981100
TI  - Airway epithelial damage induced by sulfur mustard in guinea pigs, effects of
      glucocorticoids.
AB  - Sulfur mustard (SM) represents a potential chemical warfare agent. In order to
      characterize SM-induced airway epithelial damage, we studied the effects of an
      intratracheal injection of 0.3 mg/kg of SM in guinea pigs, 5 h, 24 h, 14 days and
      35 days after exposure. During the acute period, lesions prevailed in tracheal
      epithelium exhibiting intra-epithelial blisters, inflammatory cell infiltration
      and columnar cell shedding with exposure of basal cells. Fourteen days after
      intoxication, tracheal epithelium appeared disorganized and showed a significant
      decrease in height and cell density. Tracheal epithelium recovery was still not
      complete even 35 days after SM-intoxication. At day 14, in SM-intoxicated guinea
      pigs treated with betamethasone from day 7 to day 14, epithelium height, cell
      density and cell proliferation (evaluated by immunohistochemistry) were
      significantly increased compared to untreated guinea pigs. In conclusion, the
      lesions observed in SM-intoxicated guinea pigs seem to be in accordance with
      clinical human observations and are relevant to the study of airway epithelial
      damage induced by SM. This animal model could be used to illustrate tracheal
      epithelium regeneration mainly derived from basal cells and to show
      glucocorticoid effects on airway epithelial recovery after chemical aggression.

PMID- 8981101
TI  - Interspecies differences in enzymes reacting with organophosphates and their
      inhibition by paraoxon in vitro.
AB  - 1 Inhibition of cholinesterases (ChE) and carboxylesterases (CaE) by paraoxon
      (Px) was studied in vitro in the serum, liver, lung and muscle of mouse, guinea
      pig, rabbit and man (serum only). Moreover, the role of Px hydrolyzing enzyme
      (Pxase) in the detoxification of Px was studied by inhibiting its activity with
      EDTA. 2 The ChE and CaE activities as well as their sensitivity to Px varied in
      different tissues and species. The ChEs were more sensitive than CaEs to Px
      except in the liver. The CaE activity in human and rabbit sera was low and
      resistant to Px, indicating that it may have a minor importance for the binding
      of Px. 3 The Px-inhibited ChEs were spontaneously reactivated in the mouse and
      rabbit sera during 24 h. In mouse, also the CaE activity was recovered. The
      presence of EDTA in the incubation medium prevented this reactivation indicating
      that Pxase takes part in the reactivation process. 4 In rabbit, the serum Pxase
      activity was very high suggesting a good Px detoxifying capacity of the rabbit
      serum. 5 The results show that amounts and sensitivities of esterases to OPs in
      rodents may markedly differ from that in man. Possible species-related
      differences in the affinity of ChEs and CaEs for OPs and the OP hydrolyzing
      activity should be taken into the consideration, when animal data are
      extrapolated to man.

PMID- 8981102
TI  - Hockey stick or boomerang.

PMID- 8981103
TI  - Patients must be a virtue.

PMID- 8981104
TI  - Acute or grave accentuation.

PMID- 8981105
TI  - Family balancing as a morally acceptable application of sex selection.

PMID- 8981106
TI  - Sex selection: the right way forward.

PMID- 8981107
TI  - Male infertility and ICSI: are there limits?

PMID- 8981108
TI  - Ethical and biological problems of the preimplantation genetic diagnosis for
      older mothers.

PMID- 8981109
TI  - Ethics of oocyte donation are challenged by the health care system.

PMID- 8981110
TI  - A national oocyte donation society is needed.

PMID- 8981111
TI  - Oocyte donation using "known' donors: it may seem the convenient answer but who
      pays?

PMID- 8981112
TI  - Are there genetic risks associated with microassisted reproduction?
AB  - Of all the techniques available for microassisted reproduction, the direct
      injection of individual sperm cells or spermatids into the cytoplasm of the
      oocyte (ICSI) is the most invasive, through which any possible selection against
      sperm cells with genomic defects would be excluded. It has, however, been shown
      that such a possible selection is present neither in the female genital tract nor
      at the zona pellucida. Selection against genetic-based defects occurs after the
      fertilization of the oocyte, during both embryonic and fetal development. Based
      on the data to date, it can be assumed that ICSI would not result in either a
      significant increase in genetic-based diseases, or in an increase in the number
      of infertile males. If, however, mutations of X-chromosomal or Y-chromosomal
      genes should play a major role in male fertility disorders, one could expect,
      over generations, an increase, though probably very slight, in the number of
      males with such disorders.

PMID- 8981113
TI  - Sex determination and the maternal dominance hypothesis.
AB  - The maternal dominance hypothesis has been derived from work with humans which
      shows that women who are more dominant than other women are more likely to
      conceive sons. In both animals and humans dominance is a characteristic or
      personality trait, underpinned by testosterone and responsive to a range of
      environmental changes: physical, social and psychological. Studies of the sex
      ratio in the social sciences and animal behaviour either support or are
      compatible with the idea that the sex-determining role of X- and Y-chromosome
      bearing spermatozoa may be preceded by factors under maternal control which
      provide for differential access of spermatozoa. Findings in reproductive
      physiology and physiological psychology suggest that follicular testosterone or a
      related hormone may play a critical role. Reproductive physiologists have already
      identified maternal mechanisms which could provide the context for such a model.

PMID- 8981115
TI  - Preconceptional and gestational evaluation of insulin secretion in patients with
      polycystic ovary syndrome.
AB  - The relationship between insulinaemia and obesity and glucose tolerance and the
      impact of pregnancy as risk factor for carbohydrate abnormalities were
      investigated in 91 consecutive patients with polycystic ovary syndrome (PCOS)
      aged 26-32 years. Fifteen normoglycaemic patients became pregnant within 6 months
      of the pregestational study using pharmacological induction of ovulation. Plasma
      concentrations of insulin and glucose after an oral glucose tolerance test (OGTT)
      were determined by immunoradiometric assay and glucose oxidase technique
      respectively. OGTT patients were classified according to their response as
      normoinsulinaemic (n = 46) or hyperinsulinaemic (n = 45). Impairment of glucose
      metabolism occurred in 12.1% (n = 11, 10 obese and one lean) of all PCOS
      subjects. Based on insulin secretion, 6.5% of normoinsulinaemic and 13.3% of
      hyperinsulinaemic patients had an impaired glucose tolerance and 2.3 and 2.2%
      respectively a non-insulin-dependent diabetes mellitus. Obese patients had higher
      values for area under the curve for insulin response to OGTT (I-AUC values) than
      lean patients, and the percentage above ideal body weight was greater in
      hyperinsulinaemic than in normoinsulinaemic patients. All hyperinsulinaemic
      (7/15) subjects who became pregnant developed an impairment of glucose metabolism
      during pregnancy. It is concluded that the PCOS population was at higher risk of
      developing carbohydrate abnormalities than the normal population of a similar
      reproductive age. Furthermore, those with abnormal insulin secretion at the
      pregestational stage may, during pregnancy, develop an impaired gestational
      glucose tolerance or gestational diabetes.

PMID- 8981114
TI  - Acarbose reduces elevated testosterone serum concentrations in hyperinsulinaemic
      premenopausal women: a pilot study.
AB  - In seven hyperinsulinaemic, hypertestosteronaemic premenopausal patients, we
      tested the effect of an attenuation of insulin serum concentrations by long-term
      treatment with the enteral disaccharidase inhibitor acarbose on serum
      concentrations of total and free testosterone, dehydroepiandrosterone sulphate
      (DHEAS) and sex hormone-binding globulin (SHBG). The subjects showed typical
      features of hyperinsulinaemia-hypertestosteronaemia syndrome, including elevated
      concentrations of insulin and testosterone, normal concentrations of DHEAS and
      suppressed SHBG concentrations. The patients were orally treated with an initial
      dosage of 50 mg acarbose/ day, which was gradually increased to a maximum of 300
      mg/day. Blood was sampled at week 6 (under a dosage of 150 mg acarbose/day) and
      at week 20 of treatment. A significant reduction in the increase of glucose and
      insulin concentrations, determined after administration of a standard oral 100 g
      glucose load, was found at week 6 (P < 0.02, P < 0.00007) and at week 20 (P <
      0.04, P < 0.003) of therapy and was associated with a significant decrease of
      total and free testosterone at week 20 (P < 0.04, P < 0.01). Concentrations of
      both DHEAS and SHBG remained nearly unchanged. In conclusion, it was shown that a
      decline of ovarian hypertestosteronaemia was achieved in association with a
      flattening of the postprandial glucose and insulin increase by long-term
      treatment with acarbose. Side effects were limited to abdominal distension and
      flatulence and were absent using a low dosage of 50 mg acarbose/ meal (3 x 50
      mg/day).

PMID- 8981116
TI  - Nuclear maturity and oocyte morphology after stimulation with highly purified
      follicle stimulating hormone compared to human menopausal gonadotrophin.
AB  - Several studies have shown that high concentrations of luteinizing hormone (LH)
      in the follicular phase of stimulation can have a negative effect on oocyte
      quality, pregnancy rate and incidence of miscarriage. The aim of the present
      study was to examine the effects of highly purified follicle stimulating/hormone
      (FSH HP) on ovarian stimulation and particularly on nuclear maturity and
      morphological appearance of the oocyte in intracytoplasmic sperm injection (ICSI)
      therapy and to compare the results with human menopausal gonadotrophin (HMG)
      stimulation. For this purpose, 50 patients for ICSI (HMG: 30; FSH HP: 20) and 26
      patients for in-vitro fertilization (IVF; HMG: 14, FSH HP: 12) were stimulated
      with either HMG or FSH HP using a short-term protocol. Patients were divided into
      the two groups according to the first letter of their family name. No differences
      were observed among the groups in relation to patient age, duration of
      stimulation, number of aspirated oocytes or maturity of the oocyte-cumulus
      complex. After removal of the cumulus-corona cells in the ICSI oocytes, a
      significantly higher proportion of oocytes in the FSH HP group were nuclear
      mature (metaphase II) than in the HMG group (FSH HP: 88.8%, HMG: 80.6%; P =
      0.009). Furthermore, in the FSH HP group, significantly fewer oocytes with dark
      cytoplasm were observed (FSH HP: 14.4%, HMG: 22.4%; P = 0.02). Fertilization,
      cleavage and pregnancy rates (FSH HP 38%, HMG: 34% per retrieval) were comparable
      in both groups. Based on the results obtained, it can be concluded that the short
      term FSH HP treatment protocol synchronizes oocyte maturation better than
      comparable stimulation with HMG.

PMID- 8981117
TI  - Vasopressin and atrial natriuretic hormone response to hypertonic saline during
      the follicular and luteal phases of the menstrual cycle.
AB  - We studied the hormonal responses to hypertonic saline during the follicular
      (days 2-9) and luteal (days 21-28) phases of the menstrual cycle in nine healthy
      young women, aged 19-25 years. On both study days, each woman was infused with 5%
      hypertonic saline for 1 h at the rate of 0.1 ml/kg/min. Serum progesterone and
      oestradiol concentrations confirmed the reported stage of the menstrual cycle. No
      difference in weight or haematocrit was observed between the two stages of the
      study for each woman. Baseline blood pressure, serum sodium, plasma osmolality,
      plasma vasopressin and thirst levels were almost identical for both stages, and
      changed to the same degree during infusion of hypertonic saline. Baseline atrial
      natriuretic hormone concentrations were higher during the follicular phase and
      became significantly higher than during the luteal phase following infusion of
      hypertonic saline. We concluded that the intravascular volume during the luteal
      phase may be effectively decreased in comparison to the follicular phase.

PMID- 8981118
TI  - Luteal phase oestradiol and progesterone levels are stronger predictors than
      follicular phase follicle stimulating hormone for the outcome of in-vitro
      fertilization treatment in women with tubal infertility.
AB  - Basal follicle stimulating hormone (FSH) in a natural cycle, FSH on cycle days 3
      and 10 in a clomiphene citrate-stimulated cycle and oestradiol and progesterone
      area under the curve (AUC) in the luteal phase of the clomiphene citrate
      stimulated cycle were evaluated as hormonal predictors for the outcome of IVF
      treatment in 53 normally cycling women with tubal infertility. The pregnant women
      had significantly fewer treatment cycles (P < 0.001) and needed fewer ampoules of
      gonadotrophins (P < 0.001). They also had more oocyte retrievals (P < 0.001),
      more oocytes per retrieval (P < 0.01), higher fertilization rate (P < 0.001) and
      more replaced pre-embryos per replacement (P < 0.01) as compared with non
      pregnant women. Significant differences were found in FSH concentrations on cycle
      days 3 (P < 0.05) and 10 (P < 0.001) after clomiphene citrate stimulation and for
      oestradiol and progesterone AUC in the luteal phase (P < 0.001) between those
      women who became pregnant and those who did not become pregnant after IVF
      treatment. Luteal oestradiol and progesterone had considerably stronger
      predictive value for the outcome of IVF treatment as compared to basal FSH and
      clomiphene citrate challenge test.

PMID- 8981119
TI  - Pure and highly purified follicle-stimulating hormone alone or in combination
      with human menopausal gonadotrophin for ovarian stimulation after pituitary
      suppression in in-vitro fertilization.
AB  - The use of pure follicle stimulating hormone (pFSH) and highly purified FSH (FSH
      HP) versus the combinations pFSH/human menopausal gonadotrophin (HMG) and FSH
      HP/HMG, respectively, was compared for stimulating follicular development after
      gonadotrophin-releasing hormone agonist (GnRHa) suppression in women undergoing
      in vitro fertilization (IVF)-embryo transfer. Two consecutive prospective,
      randomized studies were carried out at the Assisted Reproduction Unit of the
      Hospital Clinic i Provincial in Barcelona, a tertiary care setting. Two groups of
      188 (study 1) and 252 (study 2) consecutive infertile patients respectively,
      scheduled for IVF-embryo transfer were included. Pretreatment with leuprolide
      acetate (long protocol) was followed by gonadotrophin treatment in all patients.
      In study 1, 92 patients received i.m. pFSH alone (group pFSH) and 96 were treated
      with the combination of i.m. pFSH and i.m. HMG (group HMG-1). In study 2, 123
      patients received s.c. FSH-HP alone (group FSH-HP) and 129 patients were given
      the combination of s.c. FSH-HP and i.m. HMG (group HMG-2). Main outcome measures
      included follicular development, oocyte retrieval, fertilized oocytes, duration
      and dose of gonadotrophin therapy, and clinical pregnancy. There were no
      significant differences between pFSH and pFSH/HMG nor between FSH-HP and FSH
      HP/HMG cycles with regard to the number of ampoules of medication used, day of
      human chorionic gonadotrophin (HCG) administration, mean peak serum oestradiol
      concentrations, number of follicles punctured, and number of oocytes aspirated,
      embryos transferred, or pregnancies. We conclude that urinary FSH (either
      purified of highly purified) alone is as effective as the conventional
      combination of urinary FSH/HMG for ovarian stimulation under pituitary
      suppression in IVF cycles. Therefore, they can be used interchangeably in IVF
      programmes.

PMID- 8981120
TI  - Normal serum uric acid concentrations in women with polycystic ovary syndrome.
AB  - Recently, an inverse correlation between serum uric acid concentrations and
      insulin sensitivity has been described in subjects with varying degrees of
      metabolic syndrome, suggesting that measurement of serum uric acid may provide a
      simple marker of insulin resistance. Several biochemical and clinical features of
      polycystic ovary syndrome (PCOS) resemble those of metabolic syndrome: women with
      PCOS are often obese; they are also at increased risk for the development of
      coronary artery disease, hypertension and diabetes mellitus. The objective of the
      present study was to analyse the usefulness of serum uric acid measurement in
      screening for the metabolic syndrome in women with PCOS. For that purpose serum
      concentrations of uric acid, insulin and triglycerides were measured in 38 women
      with PCOS and 20 weight-matched control women with regular menstrual cycles. No
      differences were found in the uric acid concentrations between the PCOS and
      control groups. The mean concentrations of triglycerides and fasting insulin were
      higher in the women with PCOS than in the healthy controls. Serum uric acid
      concentrations were inversely related to serum hormone-binding globulin (SHBG)
      concentrations, and positively with body mass index (BMI), insulin concentrations
      and testosterone:SHBG ratio in the PCOS group. Our results suggest that
      measurement of serum uric acid does not provide new means for identification of
      metabolic syndrome in patients with PCOS.

PMID- 8981121
TI  - Defective maternal-fetal interaction in a murine autoimmune model.
AB  - Anti-cardiolipin antibodies (ACA) are associated with recurrent fetal loss, but
      their role in this pathological condition is unknown. We recently developed an
      experimental mouse model of the anti-phospholipid syndrome, in which immunization
      of female mice with a monoclonal anti-cardiolipin antibody resulted in
      substantial failure of pregnancy. We observed that pre-implantation embryos
      derived from ACA-injected mothers exhibited morphological abnormalities and
      failed to implant in vitro. In the present study, we designed embryo transfer
      experiments to determine whether defective embryonic development originated as a
      maternal defect, an embryonic defect or both. Embryos (3.5 day old), taken from
      ACA- and control-immunized mothers were transferred into either an ACA- or a
      control-treated uterine environment (day 2.5 pseudopregnant females). On day 14
      of gestation the incidence of pregnancy, the average number of fetuses per female
      and fetal resorptions were assessed. The ACA-treated uterine environment was
      found to be non-supportive for the development and implantation of normal
      embryos. Moreover, embryos derived from ACA-immunized mothers, even after their
      removal from the ACA-environment and transfer to a normal uterus, remained
      deficient. These results demonstrate that both the maternal and the embryonic
      compartments were defective, as a result of previous exposure to the ACA.

PMID- 8981122
TI  - Serum markers of immune activation in women undergoing in-vitro fertilization and
      embryo transfer.
AB  - We evaluated serum concentrations of two early and sensitive markers of immune
      activation, interleukin-2 receptor (sIL-2R) and intercellular adhesion molecule-1
      (ICAM-1) in two age-matched groups of in-vitro fertilization (IVF)-embryo
      transfer women, group I (n = 26) without and group II (n = 40) with
      methylprednisolone (MPD) supplementation of the luteal phase, on the days of
      oocyte retrieval (sample A) and embryo transfer (B), and second (C) and 13th (D)
      days post-transfer and in 20 normally cycling women (controls) on the day of
      luteinizing hormone (LH) peak. No difference in the outcome of the IVF-embryo
      transfer was observed between groups I and II. In sample A, both immunomarker
      concentrations showed no significant difference between the two groups of IVF
      women, while they were significantly higher (P < 0.01) than values in controls.
      In cycles in which conception occurred, significantly higher immunomarker
      concentrations were observed in sample A of both groups I and II compared with
      those in unsuccessful cycles of the same group. A significant decrease of both
      sIL-2R and ICAM-1 was noticed in sample B only in group II (P < 0.0001 and P <
      0.001 respectively; paired t-test) that continued further in the late luteal
      phase only in the case of conception, independently of MPD supplementation. These
      data suggest that (i) due to multiple ovulations, IVF-embryo transfer women show
      elevated concentrations of sIL-2R and ICAM-1 at oocyte retrieval; (ii) since,
      even at oocyte retrieval stage, high concentrations of immunomarkers are
      associated with IVF-embryo transfer success, sIL-2R and ICAM-1 could be used as
      early indicators for conception cycles; (iii) transient suppression of T cell
      activity by MPD supplementation following IVF-embryo transfer does not improve
      pregnancy rate.

PMID- 8981123
TI  - Chlamydia trachomatis antibody titres by enzyme-linked immunosorbent assay are
      useful in predicting severity of adnexal adhesion.
AB  - The aim of this study was to investigate the relationship between chlamydia
      infection and adnexal adhesion. A total of 131 infertile women who were otherwise
      asymptomatic underwent chlamydia antibody testing and laparoscopy. These women
      had additional infertility factors. Serum concentration of anti-Chlamydia
      trachomatis immunoglobulins G and A were determined prospectively by means of an
      enzyme-linked immunosorbent assay (ELISA). Results were compared with the tubal
      patency and severity of adnexal adhesion. Sensitivity, specificity, positive and
      negative predictive value, and likelihood ratios of anti-C.trachomatis antibody
      titres for the presence of adnexal adhesion were calculated. Patients who were
      positive for chlamydia antibody had a significantly higher incidence of tubal
      occlusion than those who were negative (47.1 versus 25.0%). Adnexal adhesion
      scores were significantly higher in the patients who were positive for chlamydia
      antibody than those in patients who were negative (17.1 versus 8.5). Adnexal
      adhesion scores were significantly correlated with anti-chlamydia antibody titre
      by ELISA [immunoglobulin (Ig) G: r = 0.60, Ig A: r = 0.61]. As the antibody titre
      by ELISA rose, the specificity, positive predictive value and the positive
      likelihood ratio all increased. In conclusion, C.trachomatis antibody testing is
      a simple and inexpensive means of predicting pelvic damage and laparoscopic
      examination may be recommended for patients with high anti-C.trachomatis antibody
      titres by ELISA.

PMID- 8981124
TI  - Is total laparoscopic hysterectomy a safe surgical procedure?
AB  - Total hysterectomy via laparoscopy is a recently developed technique. Assessment
      of a new surgical technique, once the operation has been shown to be feasible,
      requires an evaluation of the risks of complications. Here we report our
      cumulative 3 year experience with laparoscopic hysterectomy in a total of 222
      patients. The overall complication rate was 10.0%. We did not observe any
      haemorrhage complications requiring another operation. Four patients (1.8%) were
      re-admitted to hospital but only two of them (0.9%) had to be operated upon again
      (one vesico-vaginal fistula and one vaginal cuff wound separation). These
      encouraging results mean that, provided the surgeons are experienced in
      laparoscopic surgery, total laparoscopic hysterectomy technique would appear not
      to have a higher rate of complications than hysterectomy via laparotomy or the
      vaginal route.

PMID- 8981125
TI  - Oocyte shortage for donation may be overcome in a programme with anonymous
      permutation of related donors.
AB  - Difficulty in recruiting donors plays a crucial role in oocyte donation
      programmes. We report here an original strategy to overcome this problem,
      consisting of sharing out anonymous oocytes between recipients, which has
      markedly improved treatment efficiency by avoiding freezing or destruction of
      supernumerary embryos. Each patient received part of the supply of oocytes from
      several donors in four successive cycles, while each donor underwent oocyte
      retrieval only once. This strategy led to one pregnancy per treated donor,
      increased treatment efficacy by 300%, and reduced dramatically the oocyte
      shortage at our centre. The system avoids wastage of the rare and precious
      donated oocytes, increases the chance of pregnancy for each related recipient and
      even permits the inclusion of some recipients without related donors.

PMID- 8981127
TI  - Enhancement of outcome from intracytoplasmic sperm injection: does co-culture or
      assisted hatching improve implantation rates?
AB  - In two separate prospectively randomized trials, intracytoplasmic sperm injection
      (ICSI) cycles were studied in a controlled manner to monitor the effects of
      either bovine oviductal epithelial cell co-culture (n = 119) or assisted hatching
      by zona drilling (n = 100). In the first study, immediately following ICSI, all
      eggs were placed directly either onto partial monolayers of bovine oviductal
      cells or into regular culture medium. Although the embryo developmental rate was
      apparently compromised in part by the presence of the co-culture cells,
      ultimately there were no significant differences in either the viable pregnancy
      rate (31.6% co-culture versus 29.0% control) or the embryonic implantation rate
      (11.4% co-culture versus 13.6% control). Assisted hatching also had no
      significant impact on ICSI cycle outcome in terms of either the viable pregnancy
      rate (30.0% assisted hatching versus 32.0% control) or the embryonic implantation
      rate (8.5% assisted hatching versus 13.5% control). However, in female patients
      aged > or = 35 years, assisted hatching appeared to convey a marginally
      significant benefit in terms of both the viable pregnancy rate (35.5% assisted
      hatching versus 11.1% control) and the embryonic implantation rate (10.3%
      assisted hatching versus 3.1% control). It seems that the overall improvement of
      ICSI cycle outcome cannot be achieved by the general application of either co
      culture or assisted hatching. Nevertheless, it is possible that there remain
      specific patient groups that might benefit from selected use of either of these
      modalities.

PMID- 8981126
TI  - Beneficial aspects of co-culture with assisted hatching when applied to multiple
      failure in-vitro fertilization patients.
AB  - A study was conducted on patients who had attempted and failed previous in-vitro
      fertilization (IVF) procedures an average of 3.8 times following the application
      of assisted hatching with conventional culture systems. The aim of this
      investigation was to determine if addition of co-culture methodologies could
      reduce embryonic abnormalities and thus improve the prognosis for pregnancy. The
      study population consisted of 123 patients, subdivided into three patient
      categories. Previous IVF results from conventional culture were used to evaluate
      any potential benefits derived from the present co-culture application. Following
      co-culture, the rate of blastomere development was increased and the rate of
      fragmentation decreased. An increased rate of blastomere development was most
      noticeable in the patients aged < or = 39 years with no male factor as well as
      the intracytoplasmic sperm injection (ICSI) subgroup. Similarly, the rate of
      fragmentation was significantly reduced in the aforementioned subgroups. The most
      pronounced impact of co-culture was on pregnancy and implantation rates. The
      overall clinical and ongoing pregnancy rates were 38% (47/123) and 36% (44/123)
      respectively. The corresponding implantation rate was 17% (72/ 412) as shown by
      embryonic cardiac activity. The ongoing pregnancy rates in the < or = 39 years no
      male factor, > or = 40 years no male factor and ICSI no age limit patient
      subgroups were 41% (21/51), 30% (8/27) and 33% (15/45) respectively. The results
      indicate that addition of co-culture to the IVF procedure for poor-prognosis
      patients may be advisable.

PMID- 8981128
TI  - High tubal damage grade is associated with low pregnancy rate in women undergoing
      in-vitro fertilization treatment.
AB  - In order to analyse the relationship between grade of tubal damage and pregnancy
      rate following in-vitro fertilization (IVF) treatment, 50 consecutive couples
      with isolated tubal infertility who underwent IVF without previous reconstructive
      surgery were studied. The couples had tried to conceive for 2.5-5.6 years (mean
      3.9 years) and had gone through a complete investigation for infertility. All
      women fulfilled the standard criteria for normal ovulatory cycles. All males had
      normal spermiograms. Tubal function was in each case evaluated by
      hysterosalpingography and laparoscopy. Grade of tubal damage was classified on a
      scale of I-IV. Patients with milder tubal damage (groups I-II) showed
      considerably higher take-home baby rate per started cycle (48%) than patients
      with severe tubal damage (group IV; 6%) (P < 0.001) even though patients in group
      IV underwent more treatment cycles than patients in groups I-II (2.7 versus 1.8;
      P < 0.01). In the first treatment cycle nine out of 12 patients in groups I-II
      became pregnant as compared with only one out of 16 in group IV (P < 0.01). As
      indicators of lower ovarian response, the women in group IV needed a higher
      number of gonadotrophin ampoules per cycle (P < 0.001) and exhibited lower pre
      ovum retrieval oestradiol concentrations (P < 0.001). Oocyte retrievals per
      started cycle (I-II: 100%; III: 98%; IV: 84%) did not differ significantly
      between the groups, neither did pre-embryo replacements (I-II: 95%; III: 80%; IV:
      73%) nor pre-embryos per replacement (I-II: 3.0; III: 2.9; IV: 2.8). The present
      results concerning the role of tubal damage grade for the outcome of IVF
      treatment should be considered in patient counselling. Further studies are needed
      to elucidate the mechanisms by which the extent of tubal damage may impair
      ovarian function and reduce IVF outcome.

PMID- 8981129
TI  - Severe ovarian hyperstimulation syndrome (OHSS) and icterus.
AB  - Severe ovarian hyperstimulation syndrome (OHSS) leads to changes in laboratory
      analyte concentrations. Whereas elevated aminotransferase activity is often
      observed, a cholestatic course with hyperbilirubinaemia and icterus seldom
      occurs. In this report, the case of a 33 year old patient with polycystic ovary
      syndrome (PCOS) is described who, after stimulation with human menopausal
      gonadotrophin (HMG), developed severe OHSS with haemoconcentration, ascites,
      hydrothorax, elevated aminotransferases, hyperbilirubinaemia and icterus. The
      patient did not become pregnant and the OHSS regressed, together with the
      normalization of laboratory and clinical parameters and disappearance of the
      icterus. During the course of an OHSS cholestasis with icterus may occur, which
      could be explained by a reactive cholestatic hepatosis as a reaction to the
      hormonal changes induced by the stimulation therapy.

PMID- 8981130
TI  - The cervico-vaginal epithelium during 20 cycles' use of a combined contraceptive
      vaginal ring.
AB  - The aim of the study was to evaluate the influence of a combined contraceptive
      vaginal ring (CCVR) made of Silastic on the cervico-vaginal epithelium during 20
      cycles of use. A total of 76 volunteers used the CCVR releasing 0.120 mg
      etonogestrel and 0.015 mg ethinyloestradiol daily. Cytological samples were taken
      of the vaginal epithelium, the ectocervix and the endocervix before the start, at
      4 and 12 months, and at the end of the study. Cytology, hormonal profiles, human
      papilloma virus (HPV) status, DNA-flow cytometry, bacterial flora, and
      morphometry was performed on these samples. Colposcopy and histopathology of
      biopsy specimens were performed at the end. No cytological changes of the
      squamous epithelium or the columnar epithelium were found. HPV was detected in
      three samples of three different women. At least two of them reverted to HPV
      negative during the rest of the study period. Aneuploidy was diagnosed in 11
      women before the study. Seven of them changed to diploid during the study. No
      changes from diploid to aneuploid were seen. Aneuploidy was not seen in any of
      the HPV positive samples. Although bacterial flora showed considerable variation
      during the study, no significant influence of the CCVR could be established.
      Morphometrical analysis showed an increasing nucleus:cytoplasm ratio of the
      squamous cells during the study. Mild dysplasia was detected in one woman at the
      end of the study. It was concluded that no unfavourable cytological or
      bacteriological changes of the cervico-vaginal epithelium were demonstrated
      during 20 cycles of CCVR use. The vaginal epithelium became more progestogenic
      during the study.

PMID- 8981131
TI  - Ethinyl oestradiol plus dl-norgestrel or levonorgestrel in the Yuzpe method for
      post-coital contraception: results of an observational study.
AB  - This observational study compares the efficacy and incidence of side-effects
      between dl-norgestrel (2 mg) and levonorgestrel (1 mg) associated with ethinyl
      oestradiol (200 micrograms) given in two doses 12 h apart for emergency post
      coital contraception. A total of 117 consecutive women were given dl-norgestrel
      in combination with the oestrogen (dl-norgestrel group) while 423 consecutive
      subjects received the combination ethinyl oestradiol/levonorgestrel
      (levonorgestrel group). Overall, four (0.8%) pregnancies occurred in the 540
      treated women, one (0.9%) in the dl-norgestrel group and three (0.7%) in the
      levonorgestrel group. In addition to this similar high contraceptive efficacy
      between both study groups, women in the levonorgestrel group had a significantly
      lower incidence of side-effects (23.5%) and better timing of the next
      menstruation after treatment (75% had bleeding on time) than those in the dl
      norgestrel group (corresponding figures were 50.5 and 62.6% respectively). It is
      concluded that levonorgestrel should be used in preference to dl-norgestrel for
      post-coital contraception in the Yuzpe regimen.

PMID- 8981132
TI  - Insulin-like growth factor-I and alpha 2-macroglobulin in seminal plasma
      correlate with semen quality.
AB  - Insulin-like growth factor-I (IGF-I) and alpha 2-macroglobulin (alpha 2-M) are
      believed to be involved in the development of germ cells. IGF-I is mainly
      controlled by concentrations of human growth hormone (HGH), influences cell
      proliferation and differentiation and its action is mediated by insulin-like
      growth factor-binding proteins (IGFBP), placental protein 14 (PP14) and prostate
      specific antigen (PSA). alpha 2-M acts as a broad spectrum proteinase inhibitor
      and a binding protein for many cytokines and hormones, e.g. inhibin and activin.
      This study was designed to identify concentrations of these molecules in seminal
      plasma in normal semen samples of healthy men, correlations with semen quality,
      the relationship of IGF-I and alpha 2-M with factors affecting male fertility,
      and whether vasectomy influences the concentrations of these molecules.
      Concentrations of IGF-I and alpha 2-M in human seminal plasma were related to
      semen quality, basal concentrations of HGH, testosterone, IGFBP-3, soluble
      fibronectin receptor (sFNR), PSA and PP14 in seminal plasma and to serum
      concentrations of luteinizing hormone (LH) and follicle stimulating hormone
      (FSH). Commercially available assays were used to analyse 69 semen samples of
      various quality and 11 post-vasectomy samples. IGF-I concentrations in seminal
      plasma were significantly correlated with the percentage of morphologically
      normal spermatozoa (r = 0.748, P = 0.00001) and sperm concentration (r = 0.301, P
      = 0.011), but negatively correlated with serum FSH (r = -0.506, P = 0.00006) and
      PSA in seminal plasma (r = -0.388, P = 0.00009). Total alpha 2-M was
      significantly correlated with sperm count (r = 0.423, P = 0.0005), percentage of
      progressively motile spermatozoa (r = 0.444, P = 0.00019), quality of motility
      (sperm motile efficiency, r = 802, P = 0.00001) and straight line velocity (r =
      0.411, P = 0.0013). Correlation between the sperm concentration and HGH in
      seminal plasma was weak (r = 0.287, P = 0.015). Vasectomy reduced the
      concentration of total alpha 2-M (P = 0.00008) and HGH (P = 0.0068) in the
      seminal plasma; IGF-I was also reduced after vasectomy when the total ejaculate
      amount was considered. Thus IGF-I and alpha 2-M are significant for the germ cell
      development: IGF-I in the maturation of spermatozoa and alpha 2-M in progressive
      motility.

PMID- 8981133
TI  - Preferences for intracytoplasmic sperm injection versus donor insemination in
      severe male factor infertility: a preliminary report.
AB  - With the advent of intracytoplasmic sperm injection (ICSI), our programme noted a
      drop in the number of couples using donor insemination (DI) for severe male
      factor infertility. Over the first 8 months in which our infertility programme
      offered both treatments, 27 consecutive couples scheduled for ICSI and 15
      consecutive couples scheduled for DI were evaluated Since all patients in our
      infertility programme beginning in-vitro fertilization (IVF) with planned ICSI or
      starting DI undergo a semi-structured psychological interview, the psychologist's
      clinical notes as well as the medical chart were reviewed and coded
      retrospectively to determine factors related to a couple's treatment choice.
      Couples who chose IVF-ICSI over DI had a higher occupational status and included
      husbands with higher educational levels. Their most common motivation was to have
      the husband's biological child (93% of couples in the ICSI group). The most
      common motivation for choosing DI (60% of DI couples) was that IVF was not
      financially affordable. Choice of treatment was not related to psychological
      adjustment, the husband having prior biological children, or his risk of passing
      on a genetic defect to offspring. These preliminary data raise the concern that,
      with the success of ICSI, DI may change in the USA from being an option dictated
      by semen quality to a second choice treatment utilized for economic reasons.

PMID- 8981134
TI  - Effects of sperm activity on zinc and fructose concentrations in seminal plasma.
AB  - Attempts to correlate zinc and fructose concentrations in seminal plasma with
      andrological parameters have produced inconsistent results. To assess further
      this relationship, a prospective study was performed measuring zinc and fructose
      concentrations in seminal plasma in 1178 patients referred for fertility
      treatment. Seminal analysis was performed with biochemical measurements of
      seminal zinc and fructose. The main outcome measures were the correlation between
      motile sperm concentration and seminal zinc and fructose concentrations. Zinc
      concentrations were not influenced by the motile sperm concentration (r = 0.039).
      Fructose concentrations were found to be negatively correlated with motile sperm
      concentration (r = 0.062). We conclude that seminal plasma zinc is an unreliable
      marker of spermatogenic activity. While there does appear to be a negative
      correlation between seminal plasma fructose concentrations and motile sperm
      concentration this relationship is far from linear. Due to the biochemical
      complexity of seminal fluid attempts to perform such simple correlations between
      seminal plasma components and andrological parameters are likely to produce
      inconsistent results and their role in the assessment of sperm function must
      therefore be called into question.

PMID- 8981135
TI  - The effect of chromatin condensation (aniline blue staining) and morphology
      (strict criteria) of human spermatozoa on fertilization, cleavage and pregnancy
      rates in an intracytoplasmic sperm injection programme.
AB  - The main purpose of this study was to determine the possible relationship between
      chromatin condensation (Aniline Blue staining), the morphology of spermatozoa
      according to strict criteria, and the fertilization, cleavage and pregnancy rate
      in an intracytoplasmic sperm injection (ICSI) programme. A total of 60 patients
      were divided into two groups (27 versus 34) according to sperm stainability by
      Aniline Blue. The first group involved patients having a positive Aniline Blue
      staining test with 0-29% stained. The fertilization rate in this group was 60.8%,
      cleavage rate 54.4% and pregnancy rate 18.5%. In the second group in which > 29%
      spermatozoa were positively stained, the fertilization rate was 62.1%, cleavage
      rate 62.0% and pregnancy rate 35.3%. There was no statistically significant
      difference between the two groups. Furthermore, the influence of morphology
      according to strict criteria after Papanicolaou staining on successful
      fertilization, cleavage and pregnancy was studied in 85 patients who were divided
      into two groups according to the percentage of morphologically normal sperm. The
      fertilization, cleavage and pregnancy rates were 44.21, 63.37, and 39.47%
      respectively in the first group (< 4%), the corresponding values for the second
      group (> 4%) were 56.50, 46.04 and 21.21%. There was no significant correlation
      between the fertilization (P = 0.722), cleavage (P = 0.519) and pregnancy (P =
      0.096) rates in either group. This study demonstrates that neither chromatin
      condensation (Aniline Blue staining) nor morphology could assess the
      fertilization potential, cleavage and pregnancy rate in an ICSI programme.

PMID- 8981136
TI  - Pregnancy resulting from intracytoplasmic injection of spermatozoa from a frozen
      thawed testicular biopsy specimen.
AB  - A testicular biopsy specimen was taken in connection with scrotal exploration of
      a healthy 35 year old man who had azoospermia. Bilateral severe scarring of
      unknown aetiology was found in the exploration, and no epididymal spermatozoa
      could be obtained. Spermatozoa from the fresh biopsy specimen were used for
      intracytoplasmic sperm injection (ICSI) on the same day. Two-embryo transfer
      resulted in biochemical pregnancy. The rest of the biopsy specimen was frozen as
      small pieces of tissue using glycerol as a cryoprotectant. ICSI was then
      performed with spermatozoa prepared from the frozen-thawed tissue. One embryo was
      obtained and transferred. The transfer resulted in pregnancy, and a living fetus
      was seen in ultrasound scans at the seventh and 16th weeks of pregnancy. It is
      possible to avoid repeated testicular biopsies by using cryopreservation of
      testicular tissue.

PMID- 8981137
TI  - Changes in motility patterns during in-vitro culture of fresh and frozen/thawed
      testicular and epididymal spermatozoa: implications for planning treatment by
      intracytoplasmic sperm injection.
AB  - The present report describes the motility changes in vitro (percentage motile and
      progressively motile) of freshly collected testicular and epididymal spermatozoa
      and following freeze/thaw of the same spermatozoa from a man with obstructive
      azoospermia. Washed spermatozoa were cultured in micro droplets under paraffin
      oil or in test tubes using HEPES-buffered or bicarbonate-buffered medium
      containing 10% human serum. In fresh testicular sperm cultures 60-65% of the
      sperm cells became motile within 2 days of culture; the motility was maintained
      for a further 4-5 days before a decline was observed. The progressive motility
      improved markedly on the third day of culture and it peaked around day 5. Only a
      small number of frozen/thawed testicular spermatozoa became motile during in
      vitro culture (15-20%) and the motility was maintained for only 2-3 days before
      it declined. Furthermore, only 10-12% of the spermatozoa showed progressive
      motility. Spermatozoa recovered from micro-epididymal sperm aspiration (MESA)
      showed a gradual decrease in progressive motility and in 5 days all sperm cells
      were found to be immotile in both freshly collected and frozen/thawed
      spermatozoa. All culture systems supported sperm motility. It is clear that
      testicular spermatozoa, particularly from men with obstructive azoospermia, can
      be collected and maintained in vitro for up to 1 week before the oocyte retrieval
      but when frozen testicular or epididymal spermatozoa are used it is more reliable
      to thaw these spermatozoa on the day of intracytoplasmic sperm injection.

PMID- 8981138
TI  - Symmetry and ovulation in women.
AB  - Women have cryptic ovulation, and self-observation methods of determining the
      timing of ovulation, such as monitoring cervical mucus symptoms or recording
      basal body temperature, are not reliable. It has recently become apparent that
      the symmetry of paired soft tissue traits, such as breast size and digit length,
      changes across the menstrual cycle. This paper presents evidence that symmetry in
      four paired soft tissue traits showed a marked increase on the day of ovulation.
      The difference (i.e. the asymmetry) between the size of the left and right trait
      in ears, 3rd, 4th and 5th digits was measured. The timing of ovulation was
      confirmed by real-time pelvic ultrasonography and trait measurements were made
      without knowledge of scan results. Asymmetry was lowest on the day of ovulation
      (day 0), decreasing by about 30% from day -1, and significant within-subjects
      changes occurred from days -2 to day -1, and day -1 to day 0. The practical and
      evolutionary implications of these findings are discussed.

PMID- 8981139
TI  - Intraovarian blood flow during spontaneous and stimulated cycles.
AB  - This study was undertaken to investigate intraovarian blood flow during the early
      follicular, periovulatory and mid-luteal phases, during spontaneous and
      stimulated ovarian cycles. Transvaginal ultrasonography with colour flow imaging
      was used to measure the pulsatility index in eight patients with spontaneous
      cycles, 20 patients undergoing induction of ovulation with clomiphene citrate and
      11 patients undergoing controlled ovarian hyperstimulation for in-vitro
      fertilization (IVF)-embryo transfer with gonadotrophin-releasing hormone
      analogue, human menopausal gonadotrophin, human chorionic gonadotrophin. All
      patients were studied during the early follicular, periovulatory and mid-luteal
      phase. Intraovarian blood flow velocity waveforms were found in 20% of cases at
      the early follicular phase, in 56% during the periovulatory phase and in 85%
      during the mid-luteal phase (P < 0.001). Pulsatility index at the early
      follicular phase was found to be 1.05 +/- 0.22, during the periovulatory phase
      0.99 +/- 0.22 and during the mid-luteal phase 0.85 +/- 0.22. The appearance of
      intraovarian flow velocity waveforms may suggest either ovarian
      neovascularization or final follicular maturation or luteinization, which can be
      detected or measured by Doppler technology.

PMID- 8981140
TI  - Nitric oxide concentrations in the follicular fluid and apoptosis of granulosa
      cells in human follicles.
AB  - To study the relationship between follicular atresia, apoptosis, and nitric oxide
      (NO) generation in follicular development, steroidogenesis, NO levels in
      follicular fluid and apoptosis were analysed in the various sized follicles of
      women receiving ovarian stimulation with human menopausal gonadotrophin (HMG)
      human chorionic gonadotrophin (HCG) treatments for in-vitro fertilization (IVF)
      embryo transfer. The follicles were divided into three groups by diameter: large
      follicle, > or = 18 mm; medium follicle, > or = 12 and < or = 15 mm; small
      follicle, < or = 10 mm. Follicular fluid was obtained from 20 women 34 h after
      HCG administration, and the concentrations of oestradiol, progesterone and
      testosterone, and nitrite, nitrate, arginine and citrulline were measured.
      Granulosa cells obtained from each group of follicular fluid were stained with
      Hoechst dye, and nuclear morphology was examined by a fluorescence microscopy.
      Oestradiol and progesterone concentrations in large follicles were significantly
      (P < 0.01) higher than those in medium or small follicles, and testosterone
      concentrations in small follicles were significantly (P < 0.01) higher than those
      in large follicles. There were no significant differences in the concentrations
      of nitrite, nitrate, arginine and citrulline among three groups. The percentage
      of apoptotic cells with nuclear fragmentation was significantly (P < 0.01) higher
      in small follicles than in large follicles. The present results suggested that
      small follicles with poor response to HMG may undergo atresia through apoptosis.
      No significant difference in the follicular NO level between large and small
      follicles led us to speculate on a different responsiveness to NO in these two
      types of follicles.

PMID- 8981141
TI  - Zona opening of human embryos using a non-contact UV laser for assisted hatching
      in patients with poor prognosis of pregnancy.
AB  - The aim of this study was to examine the safety and the efficiency of a 'non
      contact' UV laser to assist hatching through zona opening of human embryos.
      Between January and November 1995 we performed zona drilling for assisted
      hatching using a new laser system (PALM UV Laser microbeam), operating in a 'non
      contact' mode to create a hole in the zona pellucida of human embryos. In a
      randomized study, laser zona opening was applied on embryos from two groups of
      patients with repeated in-vitro fertilization (IVF) failures (two to four
      attempts): group A was composed of 107 patients who received mixed embryos (216
      laser-treated and 223 not treated) and group B of 72 patients who received 218
      laser-treated embryos only. Both groups were compared with a control group of 98
      patients whose embryos were not laser treated (n = 407) (group C). The mean ages
      of all groups (38.1, 38.2 and 37.8 years respectively) and the number of IVF
      attempts (two to four attempts) were similar. The resulting clinical pregnancies
      were 39 (36.4%) in group A, 32 (44.4%) in group B and 19 (19.3%) in group C. The
      implantation rates/embryo were 9.3% in A, 16% in B and 5.1% in the control group.
      In total, 17 normal babies have been delivered (10 in group A and seven in group
      B). These results show that laser zona drilling increased the pregnancy and
      implantation rates in all the treated patients. The increase was slight but
      significant in patients of group A (P < 0.01 and P < 0.02), it was even higher in
      the patients of group B (P < 0.05).

PMID- 8981142
TI  - Antioxidative capacity of preimplantation embryo culture medium declines
      following the incubation of poor quality embryos.
AB  - Total antioxidative capacity (TAC), a measure of overall free-radical scavenging
      potential, was determined by enhanced chemiluminescence in preimplantation embryo
      culture medium (PECM; pre-equilibrated Ham's F-10 medium supplemented with 7.5%
      patient's serum). Changes were evaluated in PECM TAC following a 24 h incubation
      of 66 single human embryos, as was TAC of patient's serum alone. The PECM TAC
      averaged 8.1% of the same patient's blood serum TAC. The percentage decline of
      PECM TAC over an incubation period of 24 h ranged from 0.9 to 41.7%, with a
      median of 5.5%. The decline in PECM TAC in different embryo quality groups was
      also studied. Embryos were categorized as 'good', 'fair' or 'poor' according to a
      scoring system based on an assessment of both the morphological appearance and
      developmental speed of the embryos. Incubation of poor quality embryos was
      associated with a decline in TAC, which was significantly higher than that
      observed in 'good' and 'fair' embryos. The findings suggest that impaired embryo
      development may be associated with an increased generation of reactive oxygen
      species by the embryo.

PMID- 8981143
TI  - The chromosomal complements of multipronuclear human zygotes resulting from
      intracytoplasmic sperm injection.
AB  - Implementation of intracytoplasmic sperm injection (ICSI) in human in-vitro
      fertilization (IVF) has highlighted the need for information about the risk of
      nuclear spindle damage caused by this procedure. For this purpose we studied the
      final products of oocyte meiosis at the first cleavage division of
      multipronuclear zygotes arising after ICSI, and compared the results with
      abnormally fertilized oocytes after conventional in-vitro insemination. Of 37
      successfully analysed tripronuclear zygotes, 18 had three individual metaphases.
      Abnormal complements of 11 zygotes in this group indicated that non-disjunction
      occurred predominantly at the second meiotic division of the oocytes. Nine of the
      37 tripronuclear zygotes exhibited two individual metaphases. Seven were abnormal
      and there were some indications that non-disjunction took place during oocyte
      meiosis. Of the 37 tripronuclear zygotes, 10 had a single metaphase and three
      showed an aneuploid number of chromosomes. The overall rate of aneuploidy among
      tripronuclear microinjected zygotes was 56.7%. In addition, seven zygotes with
      more than three pronuclei arising after ICSI displayed severely depleted
      chromosome complements. The incidence of non-disjunction in oocytes fertilized by
      conventional in-vitro insemination was significantly lower (20.0%, P < 0.01),
      since only four zygotes had an aneuploid number of chromosomes. Our findings
      suggest that ICSI might interfere with regular chromosome segregation at the
      second meiotic division of the oocytes.

PMID- 8981144
TI  - Undocumented embryos: do not trash them, FISH them.
AB  - Pronuclei formation is routinely assessed 16-20 h after oocyte insemination in in
      vitro fertilization (IVF). Occasionally, the pronuclei disappear before this
      time, rendering them as 'undocumented'. Since the number of pronuclei detected is
      used to distinguish normal from abnormal embryos in the context of ploidy, the
      diploidy of undocumented embryos is questionable, and therefore they are
      routinely discarded. The introduction of fluorescent in-situ hybridization (FISH)
      technology allows the assessment of ploidy status in undocumented embryos that
      continue to cleave to form blostomeres. In this study, we used FISH to analyse
      the chromosomal status of 23 undocumented embryos obtained from 10 patients.
      Biopsied blastomeres were fixed and probed for five chromosomes (X, Y, 13, 18,
      21). Diploidy was confirmed in 13 (57%) embryos while the remaining 10 embryos
      displayed various chromosomal anomalies. Six of the diploid embryos were
      transferred subsequently to the patients. One ongoing pregnancy was achieved
      following transfer of an undocumented, analysed embryo, which was already cleaved
      when assessed 20 h after insemination. We suggest that accelerated dismantling of
      the pronuclear membrane and subsequent cleavage do not necessarily indicate
      abnormal chromosomal content and may result in normal pregnancy. In a patient
      with a small number of embryos, FISH may be used to ascertain diploidy of
      undocumented embryos, thereby increasing the number of available embryos for
      transfer.

PMID- 8981145
TI  - Prolonged sperm-oocyte exposure and high sperm concentration affect human embryo
      viability and pregnancy rate.
AB  - A reduced time interval of oocyte exposure to spermatozoa was investigated to
      assess whether it could enhance oocyte development and improve embryo viability,
      especially in cases of male factor infertility. A total of 167 patients were
      included in a prospective randomized study. They were randomly allocated to two
      major study groups, A (n = 85) and B (control group; n = 82). The oocytes from
      group A patients were exposed to spermatozoa for only 1 h; those from group B
      were exposed for 16 h. The two study groups were then subdivided according to
      semen quality for further analysis of the results. Significantly higher
      percentages were obtained in group A than in group B in terms of the
      fertilization rate (74 versus 68%, P < 0.025), cleavage rate (53 versus 41%, P <
      0.005), pregnancy rate (27 versus 12%, P < 0.05) and implantation rate (11 versus
      6%, P < 0.05). In addition, an increased fertilization rate was achieved in
      oocytes exposed to male factor spermatozoa for only 1 h compared with the
      conventional incubation period (78 versus 65%, P < 0.01). Advanced cellular
      stages (55 versus 41%, P < 0.02) and higher implantation rates (13 versus 4%, P <
      0.05) were attained in the subgroup whose oocytes were exposed to normal
      spermatozoa for 1 h compared with the male factor spermatozoa with the standard
      culture interval. The higher fertilization rates, enhanced embryo development and
      viability achieved in group A indicate that prolonged exposure of oocytes to high
      concentrations of spermatozoa is detrimental, decreasing sperm-oocyte interaction
      and subsequent embryo implantation, particularly in male factor patients.

PMID- 8981146
TI  - Ultrasound derived indices of follicular blood flow before HCG administration and
      the prediction of oocyte recovery and preimplantation embryo quality.
AB  - The principal aim of the study was to relate ultrasound-derived indices of blood
      flow in individual follicles on the day of, but before, the administration of
      human chorionic gonadotrophin (HCG) to the subsequent recovery of oocytes and the
      production of preimplantation embryos. Data were obtained from 21 women (aged 29
      43 years) with bilateral tubal occlusion, who were undergoing treatment by in
      vitro fertilization (IVF) and embryo transfer. Transvaginal ultrasonography with
      colour Doppler imaging and pulsed Doppler spectral analysis were used to measure
      follicular volume and derive indices of blood flow. The end-points for each
      follicle were the volume, peak systolic velocity (PSV), pulsatility index (PI),
      and the recovery or non-recovery of an oocyte, the subsequent production or non
      production of a preimplantation embryo and the morphological grade of each
      embryo. A total of 94 follicles were studied; 74 oocytes were recovered (79%) and
      40 embryos (33 grade I or II) were produced. There were four clinical pregnancies
      (pregnancy rate 25.0% per transfer, 19.0% per patient). There was a significant
      correlation between whether or not follicular blood flow was detected and whether
      or not an oocyte was recovered (P < 0.05, chi 2 test). The values for volume and
      PI were not clinically useful. The PSV (cm/s, mean +/- SD) was higher in
      follicles that were associated with the production of an embryo (12.7 +/- 5.9)
      compared with those that were not (8.5 +/- 5.0; P < 0.05, Student's t-test). The
      probability of producing a grade I or grade II embryo was 75% if the PSV was > or
      = 10 cm/s. The corresponding value was 40% if the PSV was < 10 cm/s and 24% if
      blood flow was not detected (i.e. PSV < 3 cm/s). There was a significant increase
      (P < 0.05, Student's t-test) in the PSV before aspiration in those follicles
      associated with the subsequent production of an embryo. We conclude that the
      value for PSV, before the administration of HCG, can be used to identify
      follicles with a high probability of producing an oocyte and a high grade
      preimplantation embryo. The information may also be used to time the
      administration of HCG to achieve the optimum number and quality of embryos for
      patient management.

PMID- 8981148
TI  - Study of the intramural oviduct response to tubal and uterine distension:
      identification of tubo-uterine sphincter and reflex.
AB  - The effect of tubal and uterine distension on the intramural portion of the
      oviduct (IMO) was studied in 11 women (mean age 31.1 years). The IMO length was
      determined and the pressure response of the IMO to distension of the
      anaesthetized oviduct and uterus was examined. A 1.2 cm long high pressure zone
      (32.2 +/- 6.9 cm H2O) was identified in the IMO. An IMO pressure drop occurred
      upon oviduct distension with 2 ml of CO2 (P < 0.01); distension with greater
      volumes induced the same pressure drop (not significant). The IMO pressure
      increased with 10 ml uterine distension (P < 0.05); distension with greater
      volumes did not induce further pressure rises (not significant). Distension of
      each of the anaesthetized oviduct, uterus and IMO separately effected no IMO
      pressure response. A 'tubo-uterine' physiological sphincter is postulated at the
      high pressure zone of the IMO. It relaxes or contracts upon tubal or uterine
      distension respectively. The sphincter response to tubal or uterine distension is
      suggested to occur by a reflex action through a 'tubo-uterine' reflex, as shown
      by reproducible results and sphincteric non-response upon anaesthetization of the
      two arms of the reflex.

PMID- 8981147
TI  - Effects of daily low dose mifepristone on endometrial maturation and
      proliferation.
AB  - Following an ovulatory control cycle, six women took 2 mg of mifepristone daily
      for 30 days. Endometrial biopsies were collected in the control cycle between 7
      and 11 days after the plasma luteinizing hormone (LH) surge and on the
      corresponding day of the treatment cycle (days 19-28). In order to investigate
      the effects of unopposed oestrogen on the endometrium, persistent proliferative
      endometrium was obtained from six women with anovulatory infertility due to
      polycystic ovarian syndrome (PCOS) on a similar cycle day (days 21-23) following
      a progestogen-induced withdrawal bleed. Endometrium was evaluated for histology
      and immunolocalization of oestrogen receptors (ER), progesterone receptors (PR)
      and the cell proliferation markers [proliferating cell nuclear antigen (PCNA) and
      Ki67]. Treatment with mifepristone inhibited ovulation in four of the six
      subjects. In the two subjects in whom ovulation did occur, secretory
      transformation was delayed, suggesting that successful implantation of a
      blastocyst would be unlikely. In subjects who remained anovulatory during
      treatment, the histology and pattern of steroid receptor expression was similar
      to proliferative phase endometrium. In women with PCOS, mitoses and intense
      immunostaining for ER, PR and cell proliferation markers were observed in both
      glands and stroma. Although PCNA and Ki67 immunostaining were also present in
      mifepristone-treated endometrium from subjects who did not ovulate, there were no
      mitoses and significantly less ER immunostaining in spite of exposure to
      unopposed oestrogen for a similar duration. Since PCNA and Ki67 detect cells
      throughout all stages of the cell cycle this would suggest that mifepristone
      might affect the entry of cells into the mitotic phase of the cell cycle and,
      therefore, might prevent endometrial hyperplasia. These findings add further
      evidence to support the contraceptive potential and antiproliferative activity of
      daily low dose mifepristone.

PMID- 8981149
TI  - Transvaginal ultrasound studies of vascular and morphological changes in uteri
      exposed to diethylstilbestrol in utero.
AB  - The aim of this prospective study was to establish complementary data of uteri
      exposed to diethylstilbestrol (DES) in utero for transvaginal analysis and
      vascularity changes during the menstrual cycle. A total of 28 women with DES
      exposed uteri were compared with 60 non-exposed women. Transvaginal ultrasound
      and colour Doppler imaging were performed on days 5 and 22 of the menstrual
      cycle. Uteri were measured on sagittal and transverse scans. Uterine length,
      width, thickness and uterine cavity length and width were measured. Uterine
      volume and uterine cavity area were calculated. DES-exposed uterine volume was
      equal to 31.84 +/- 3.37 cm3. The cavity area of DES-exposed uterus was equal to
      35.85 +/- 3.93 cm2. Cervix length of DES-exposed uterus was significantly smaller
      than that of non-exposed uterus. The uterine artery pulsatility index (PI) of DES
      exposed uterus was significantly higher than that of normal uterus. Blood flow
      remained stable throughout the menstrual cycle. The PI of DES-exposed uterus
      remained stable during the menstrual cycle, as in non-exposed uterus, and it
      decreased during the luteal phase. This lack of modification in vascularity of
      DES-exposed uterus may explain miscarriages and obstetric complications such as
      intrauterine growth retardation or pre-eclampsia. The data may have implications
      for the assessment of reproductive status and the design of future studies on
      disorders of implantation in DES-exposed uterus.

PMID- 8981150
TI  - Osseous metaplasia of the endometrium: a rare cause of infertility and its
      hysteroscopic management.
AB  - This case report presents a very rare and long-standing cause of infertility,
      osseous metaplasia of the endometrium, and describes its successful management by
      hysteroscopy. A woman with a history of induced abortion 12 years ago, failed to
      conceive from that time on. The infertility work-up was unrevealing except for
      the presence of intracavitary calcification on ultrasonography. After diagnostic
      hysteroscopy, solid bony spicules covering the posterior wall of the endometrial
      cavity were removed by wire loop resectoscope. Histology established the
      diagnosis of osseous metaplasia of the endometrium. The patient conceived in her
      second spontaneous cycle and has an ongoing pregnancy at the time of writing.
      Hysteroscopy was an effective means of extracting this heterotopic tissue,
      thereby re-establishing fertility even after a long period of infertility.

PMID- 8981151
TI  - Oocyte donation to women of advanced reproductive age: pregnancy results and
      obstetrical outcomes in patients 45 years and older.
AB  - We analysed the results of oocyte donation to women of advanced reproductive age
      (> or = 45 years old) and followed their pregnancies through to delivery in order
      to assess obstetrical outcomes. Patients (n = 162) aged 45-59 years (mean +/- SD;
      47.3 +/- 3.4 years) underwent 218 consecutive attempts to achieve pregnancy.
      Oocytes (16.2 +/- 7.2 per retrieval) were provided by donors < or = 35 years old.
      Cleaving embryos (8.2 +/- 4.8 zygotes/couple) were transferred transcervically
      (4.5 +/- 1.1 per embryo transfer) to recipients prescribed oral micronized
      oestradiol and intramuscular progesterone. Following oocyte aspiration there were
      six instances of non-fertilization (2.8%) and 212 embryo transfers. A total of
      103 pregnancies was established for an overall pregnancy rate (PR) of 48.6%,
      which included 17 preclinical pregnancies, 12 spontaneous abortions, and 74
      delivered pregnancies (clinical PR 40.6%; delivered PR 34.9%). Multiple
      gestations were frequent (n = 29; 39.2% of pregnancies) and included 20 twins,
      seven triplets, and two quadruplets. Two of the triplet and both of the
      quadruplet pregnancies underwent selective reduction to twins. Antenatal
      complications occurred in 28 women (37.8% of deliveries) and included preterm
      labour (n = 9), gestational hypertension (n = 8), gestational diabetes (n = 6),
      carpel tunnel syndrome (n = 2), pre-eclampsia (n = 2), HELLP syndrome (n = 2),
      and fetal growth retardation (n = 2). 48 (64.8%) deliveries were by Caesarean
      section. The gestational age at delivery for singletons was 38.3 +/- 1.3 weeks
      (range 35-41 weeks), with birth weight 3218 +/- 513 g (range 1870-4775 g); twins
      35.9 +/- 2.0 weeks (range 32-39 weeks), birth weight 2558 +/- 497 g (range 1700
      3450 g); and triplets 33.5 +/- 0.7 weeks (range 32-34 weeks), birth weight 1775
      +/- 190 g (range 1550-2100 g). Neonatal complications (4.6% of babies born)
      included growth retardation (n = 2), trisomy 21 (n = 1), ventricular septal
      defect (n = 1), and small bowel obstruction (n = 1). There were no maternal or
      neonatal deaths. We conclude that oocyte donation to women of advanced
      reproductive age is highly successful in establishing pregnancy. However, despite
      careful antenatal screening, obstetrical complications are common, often
      secondary to multiple gestation.

PMID- 8981152
TI  - Klippel-Trenaunay-Weber syndrome associated with fetal growth restriction.
AB  - Klippel-Trenaunay-Weber syndrome is a rare congenital deep-vein malformation.
      Pregnancy in patients with this syndrome is rare and only a few cases have been
      reported. Known obstetrical risks in pregnant patients with this syndrome include
      bleeding from angiomata in the genitalia, and coagulation disturbances. We
      present a 31 year old woman with this syndrome who, on two occasions, delivered
      small-for-gestational-age neonates. This may have been due to placental
      insufficiency caused by angiomatosis related to the syndrome.

PMID- 8981154
TI  - Rapid genetic diagnosis at 7-9 weeks gestation: diagnosis of sex, single gene
      defects and DNA fingerprint from coelomic samples.
AB  - Prenatal diagnosis (chorionic villus sampling (CVS) or amniocentesis) is
      performed at a relatively late stage of pregnancy (11-18 weeks). Such tests have
      significant disadvantages including increased risk of miscarriage and delay
      before results are known. Earlier prenatal diagnosis (< 11 weeks) has been
      discontinued because of the risk of fetal abnormalities. Recently fetal cells
      have been recovered from the coelomic cavity at 7-12 weeks gestation
      (coelocentesis). This study has established that highly sensitive fluorescent
      polymerase chain reaction (PCR) can provide rapid (4-5 h), reliable and accurate
      multiple genetic diagnoses (sexing and single-gene diagnosis) from coelomic
      cells. As prenatal diagnosis has a significant risk of contamination, we have
      also shown that coelomic cells can be simultaneously DNA fingerprinted to
      determine that contamination has not occurred. This earlier method of prenatal
      diagnosis would be very valuable, as it may overcome some problems of later
      conventional prenatal diagnosis and allow reassurance/treatment to be undertaken
      at a much earlier stage. Successful application of these techniques may supersede
      alternative methods of prenatal diagnosis. Although these techniques appear very
      promising, extensive clinical trials must be undertaken to determine safety of
      coelocentesis, diagnostic reliability and accuracy in a clinical setting.

PMID- 8981153
TI  - Successful laparoscopic management of primary abdominal pregnancy.
AB  - Overall, approximately 1% of ectopic pregnancies are abdominal pregnancies, which
      can be life-threatening even when surgical intervention with laparotomy is
      performed. We present a case in which abdominal pregnancy was successfully
      managed by operative laparoscopy. A 25 year old Japanese woman presented 6 weeks
      after her last menstruation with elevated basal body temperature, lower abdominal
      pain, and light vaginal bleeding. The urinary human chorionic gonadotrophin (HCG)
      concentration was 2137 IU/I, and laparoscopic findings (i.e. the implantation
      site was the posterior serosa of the uterus with normal adnexae) established a
      diagnosis of primary abdominal pregnancy. The gestational product was completely
      removed by laparoscopic surgery with no uncontrollable loss of blood. The urinary
      concentration of HCG declined rapidly and the patient made an uneventful
      recovery. Operative laparoscopy is a safe alternative for the management of
      appropriately selected patients with early abdominal pregnancy.

PMID- 8981155
TI  - A comparison of single and married recipients of donor insemination.
AB  - There has been some controversy surrounding the use of donor insemination (DI)
      for single women. The purpose of the present study was to compare psychological
      characteristics of married versus single women who were DI recipients. A total of
      17 single women and 17 married women completed psychological questionnaires
      regarding psychiatric symptomatology, self-esteem, and their attitudes towards DI
      prior to treatment. There were no significant differences between the groups in
      psychiatric symptomatology or level of self-esteem. A significant difference was
      found in the amount of time taken to decide to use DI with single women waiting
      longer. There were no significant differences between groups in reported concerns
      about the child. There were significant differences in attitudes towards
      disclosure with more single than married women reporting that they would tell the
      child about using DI to conceive.

PMID- 8981156
TI  - Donor insemination programmes with personal donors: issues of secrecy.
AB  - This study involved 46 recipients and donors in personal donor programmes
      interviewed anonymously by postal questionnaire and interview: 38% (30/80) of
      possible recipients responded. The total number of people told about the donor
      involvement ranged between two and 78, with no significant gender difference.
      Relationships had changed for half of the participants in the programmes with 75%
      reporting that they had developed a closer relationship and 25% reporting a
      deterioration. Contact between couples and donors was seen as being in the
      original role of family friend or relative rather than as donor. An equal
      proportion of recipients (63%) and donors (78%) agreed to the donor being
      identified to any offspring although this was qualified with regard to the age of
      the child. Reasons for identification were given as avoidance of family secrets
      and the rights of the child to have information concerning their conception.
      Those who did not agree said that the child was better off not knowing, or who
      wished to preserve donor anonymity. The donor group was more likely than the
      recipients to say that identification to the child was in the best interests of
      the social parents because it allowed all those involved to feel part of a single
      family group. It was found that for both recipients and donors, the advantages
      given for having a personal donor was openness within the relationship. For the
      recipients, this focused on knowledge of the donor background and, for related
      couples, having a common genetic relationship. For donors, the advantages given
      were: knowing the child's environment, having access to a child and the ability
      to choose recipients. A disadvantage for donors and recipients was the
      possibility of a change in the relationship and for donors an added disadvantage
      was having to share in the emotional stress of the treatment and negative
      outcomes. More men than women placed importance on having a donor with a similar
      genetic background.

PMID- 8981157
TI  - Oocyte donation and oestradiol administration.

PMID- 8981158
TI  - Diagnosis of varicocele.

PMID- 8981159
TI  - Risks of third-generation oral contraceptives.

PMID- 8981160
TI  - Correlation between testicular histology and outcome after intracytoplasmic sperm
      injection using testicular spermatozoa.

PMID- 8981171
TI  - Enhancement of erectile responses to vasoactive drugs by a variable amplitude
      oscillation device.
AB  - The limitations of intracavernosal injection (ICI) of vaso-active drugs as a
      diagnostic tool in the evaluation of erectile dysfunction are well recognized
      and, prominently, include the artifacts induced by the unfamiliar environment on
      the patient. We report on the benefits of adding a vibratory stimulus to ICI to
      improve the sensitivity of this test in a population of 170 patients with
      erectile dysfunction who were evaluated using a standard protocol.
      Intracavernosal pressure was measured following ICI alone and ICI with vibratory
      stimulation of the penis. A statistically significant improvement in
      intracavernosal pressure (ICP) with the addition of vibration was observed in 87%
      of the subjects as compared to ICI. In 52% the improvement in ICP was greater
      than 20% over that achieved by ICI. This study showed that the addition of
      vibration to intracavernosal administration of vaso-active drugs significantly
      increases the erectile response in a controlled and reproducible manner.
      Vibratory stimulation provides a better reflection of erectile potential than the
      pharmacological challenge alone.

PMID- 8981172
TI  - Visual erotic and vibrotactile stimulation and intracavernous injection in
      screening men with erectile dysfunction: a 3 year experience with 406 cases.
AB  - To establish the number of patients with erectile dysfunction (ED) who appear to
      be sexually potent when exposed to visual erotic (VES) and vibrotactile
      stimulation (VIB) and to investigate whether or not older patients are less
      responsive to VES/VIB than young patients. Retrospective analysis of data on 406
      consecutive patients screened for ED with VES, VES + VIB, VES + Intracavernous
      injection (ICI). Partial or full erection was obtained in 34% of patients with
      VES, 52% with VES + VIB, 82% with VES + ICI. Men < 40 y (n = 86) responded better
      than men > 40; between 40 and 80 no differences in penile responses were found.
      50% of patients who reported no morning/night erections appeared to have good,
      rigid nocturnal penile tumescence (NPT). The use of VES, VES + VIB, VES + ICI is
      strongly recommended in the screening of men with ED of all ages; up to 80% will
      respond with a good erection. Only a positive penile response has diagnostic
      significance. The positive results reduce the necessity for further invasive
      investigations.

PMID- 8981173
TI  - A pilot study of the role of intracavernous injection of vasoactive intestinal
      peptide (VIP) and phentolamine mesylate in the treatment of erectile dysfunction.
AB  - Twenty men with chronic impotence with a mean age of 46 years (range 26-63 y)
      were treated with self administration of 0.35 ml of Vasopotin 1 and 2, a
      combination of 30 mg Vasoactive Intestinal Peptide (VIP) and either 1.0 or 2.0 mg
      Phentolamine Mesylate. All patient were assessed using a standard protocol which
      included history and examination, vibratory penile biothesiometry, colour flow
      duplex Doppler ultrasonography and where indicated, Rigiscan nocturnal penile
      tumescence testing, dynamic infusion cavernosometry and cavernosography (DICC)
      and angiography. Impotence was classified as psychogenic in six patients,
      arteriogenic in nine patients, neurogenic in two patients and cavernosal venous
      leakage in three patients. A total of 60 injections was given. After sexual
      stimulation, an erection of sufficient rigidity for intercourse occurred in six
      patients with psychogenic impotence, seven of the nine patients with arteriogenic
      impotence, two patients with neurogenic impotence and one of three patients with
      cavernosal venous leakage. No patients experienced priapism, two patients
      complained of postinjection penile pain and three patients experienced transient
      facial flushing. Intracavernous self injection of Vasopotin appears to be a
      useful treatment for erectile dysfunction.

PMID- 8981174
TI  - The use of the vacuum erection device in the management of erectile impotence.
AB  - A retrospective survey was conducted to assess the use, efficacy and acceptance
      of the Vacuum Erection Device (VED) among 60 impotent men not satisfied with
      intracavernosal injection therapy. Forty three (72%) men filled out the
      questionnaires. Thirty nine (81%) of the men abandoned the device, the main
      reason being that 'it did not work'. One possible explanation for this was
      patient selection, testing the VED on men who had previously found injection
      therapy unsatisfactory. Patients' attitudes to the device were unfavourable
      overall. Sixty four percent of men had at least one minor side effect using the
      VED, the most common being discomfort. The role of the partner for men using this
      form of treatment is unresolved. In this study, the VED was no more effective
      than injections in overcoming erectile dysfunction, but the relative advantages
      of either treatment needs to be addressed in controlled clinical trials.

PMID- 8981175
TI  - Value of nocturnal penile tumescence and rigidity (NPTR) recording in impotent
      patients with multiple sclerosis.
AB  - The etiology of impotence in patients with multiple sclerosis (MS) is difficult
      to assess due to the possibility of normal nocturnal penile tumescence and
      rigidity (NPTR) recording despite neurologic involvement. Sixteen patients with
      MS and impotence were studied with Rigiscan, cavernous artery doppler,
      neurophysiological tests and intracavernous injection of PGE1. When more
      restrictive criteria of normality than usual are used for Rigiscan (rigidity > or
      = 80% and/or duration > 30 minutes), an inverse relationship between NPTR
      recording and sexuality score or PGE1 dose is reported. No significant difference
      is noted for neurophysiological tests. With such criteria, Rigiscan alone or
      combined with intracavernous PGE1 is a valuable means to differentiate neurogenic
      from psychogenic impotence in MS patients. Neurophysiological tests are of
      limited clinical value.

PMID- 8981176
TI  - Has the efficacy of penile arterial by-pass surgery in the treatment of
      arteriogenic erectile dysfunction been determined?
AB  - The evaluation of the efficacy of penile arterial by-pass surgery (PABG) must be
      based on data obtained in clinical trials which have utilized a traditionally
      acceptable scientific design. A review of the studies which have presented the
      PABG surgical outcomes analysis revealed that patient selection and patient
      assignment have not been randomized. Demographic and individual variables, which
      could potentially influence outcomes, have not been eliminated by use of a
      marched pair design. Treatment options, including an option which allows
      assessment of effect of surgery per se, have not been presented in any of the
      studies. A majority of the studies have not blinded the researcher who analyzed
      the results. Commonly, follow-up evaluations have been limited and have not used
      converging sources of evidence. Practical suggestions are offered to improve
      future clinical trials so that the question of the efficacy of PABG surgery can
      be scientifically answered.

PMID- 8981177
TI  - Correction of congenital or acquired penile curvature through a simple
      corporoplication technique.
AB  - Sexual dysfunction resulting from penile deformity is amenable to surgical
      correction. Thirty-five cases of penile deformity either 29 congenital or six
      secondary to Peyronie's disease were treated by simple plication of the tunica
      albuginea with non-absorbable sutures through a small skin incision made on the
      convex side of the curved penis. Postoperative complications such as impaired
      erection or loss of sensitivity of the glans were not reported. After an average
      follow-up of 36 months (range 12-60 months) all patients have straight erections
      and retain normal erectile function.

PMID- 8981178
TI  - Intracorporal lengths of organically impotent men.
AB  - This report analyzes the intracorporal lengths of 236 consecutive organically
      impotent men who underwent insertion of a penile prosthesis. The average right or
      left intracorporal length in this series was 20.9 cm, with a standard deviation
      of 2.2 cm. Intracorporal length ranged from 14-27 cm. This data may be used as
      reference ranges for penile prosthesis manufacturers, and for Urologists who
      implant prostheses or perform penile lengthening procedures.

PMID- 8981179
TI  - In vitro efficacy of levofloxacin alone or in combination tested against multi
      resistant Pseudomonas aeruginosa strains.
AB  - Levofloxacin, the S(-) isomer of ofloxacin, demonstrates in vitro activity
      against Pseudomonas aeruginosa. To further characterize this activity,
      levofloxacin was tested against three populations of recent clinical isolates
      categorized by their resistance patterns to several other anti-pseudomonal
      agents. Results demonstrate the minimum inhibitory concentrations (MICs) for
      levofloxacin were generally two- to fourfold higher than for ciprofloxacin.
      Higher fluoroquinolone MICs were associated with MIC increases in other drugs.
      Levofloxacin demonstrated cross resistance against ciprofloxacin-resistant
      strains. Combinations of levofloxacin and several codrugs revealed that the
      majority of evaluable interactions demonstrated indifferent action. Levofloxacin
      exhibited enhanced activity (additive or degrees of synergy) principally with
      piperacillin, aztreonam, or ceftazidime. The synergy and additive rate (21 to
      30%) compared favorably with the enhanced interactions observed with gentamicin
      combined with piperacillin or ceftazidime (27 to 30%). Levofloxacin activity
      against P. aeruginosa was most comparable to that of ciprofloxacin, which was
      applicable against > 90% of strains found to be resistant to other classes of
      antimicrobial agents.

PMID- 8981180
TI  - In vitro activity of ampicillin-sulbactam against clinical multiresistant
      Acinetobacter baumannii isolates.
AB  - We evaluated the in vitro activity of ampicillin-sulbactam in comparison with
      that of broad-spectrum antimicrobial agents against Acinetobacter baumannii
      isolates. Two hundred and twelve clinical isolates collected between January 1993
      and March 1995 from two tertiary hospitals located in Sao Paulo, Brazil were
      tested for susceptibility by the disk diffusion method against several broad
      spectrum antimicrobial agents, including imipenem, ciprofloxacin, ceftazidime,
      aztreonam, amikacin, and polymyxin B. All strains were susceptible to polymyxin
      B. The second most active compound was the combination ampicillin-sulbactam (88%
      susceptibility). Only 79% of the isolates were susceptible to imipenem.
      Ciprofloxacin was active against 60 (28%) and amikacin against 34 (16%) isolates.
      Ceftazidime was the most active cephalosporin; however, only 9% of the isolates
      were susceptible to this compound. Both aztreonam and ampicillin alone showed
      very poor activity against this species (1% susceptibility). The prevalence of
      severe infections due to A. baumannii is increasing very rapidly in the tertiary
      hospitals of Sao Paulo and there are very few options for the treatment of these
      infections. Polymyxin B is invariably in vitro active against this species;
      however, this compound can cause severe side effects and is not commercially
      available for intravenous use in Brazil and in several other countries. Our
      results indicated that the combination ampicillin-sulbactam may be an alternative
      drug for the treatment of infections due to multiresistant A. baumannii; however,
      further studies are necessary to evaluate the clinical role of this compound for
      the treatment of severe infections.

PMID- 8981181
TI  - Transferable resistance to specific antibiotics in nosocomial strains of
      Pseudomonas aeruginosa from two teaching hospitals.
AB  - We describe the transfer of resistance to kanamycin, carbenicillin and
      cephaloridine to a recipient strain of Escherichia coli K-12 No. 3110 from three
      strains of Pseudomonas aeruginosa out of 146 strains tested in 1995. The
      P.aeruginosa No. 201, 203, 208 donor strains were isolated from patients in the
      University Clinics in Frankfurt, Germany. They were resistant to most beta-lactam
      antibiotics including cephalosporins of the 1st, 2nd and 3rd generation,
      imipenem, meropenem and aztreonam. They transferred kanamycin, carbenicillin and
      cephaloridine resistance determinants to recipient strain E.coli K-12 3110. These
      determinants were accompanied in strain P. aeruginosa No. 203, with a transfer of
      ceftazidime resistance determinants and in P.aeruginosa No. 208 with transfer of
      cefotaxime, ceftazidime and aztreonam resistance determinants. Transfer of
      antibiotic resistance was also studied in 13 nosocomial strains of P.aeruginosa
      collected for their ceftazidime and/or imipenem resistance in a large Teaching
      Hospital in Ostrava, Czech Republic. Six of these strains transferred
      carbenicillin and/or cephaloridine resistance to the E.coli K-12 3110 recipient
      strain. Resistance to kanamycin and cefotaxime was also co-transferred with
      carbenicillin and cephaloridine determinants. Ceftazidime, imipenem or ofloxacin
      resistance was not transferred and is thus, most probably, of chromosomal origin.

PMID- 8981182
TI  - Inhibitory and bactericidal activity of rokitamycin against Helicobacter pylori
      and morphological alterations.
AB  - Rokitamycin is a macrolide antibiotic, recently entered into clinical use. Its in
      vitro activity and kill kinetics against Helicobater pylori have been evaluated
      at 1 x the minimum inhibitory concentration (MIC), 2 x MIC and 4 x MIC at 2, 4,
      8, 24 hours and compared with those of clarithromycin, erythromycin and
      amoxicillin. Morphological changes in H. pylori induced by rokitamycin incubation
      at these MICs and times were also investigated by scanning electron microscopy.
      All the antibiotics tested had good inhibitory activity against H. pylori, a slow
      growing microorganism. The order of MIC activity was clarithromycin > amoxicillin
      > rokitamycin > erythromycin. Rokitamycin killed more rapidly than the other
      antibiotics, in fact H. pylori strains were totally killed at 8 h (2 x MIC) and 4
      h (4 x MIC) and after only 2 h incubation all concentrations greatly decreased
      the CFU/ml. These effects were also confirmed by the rapid appearance of surface
      and morphological alterations (focal blebs, constrictions, rounded forms) in the
      normal structure of H. pylori observed by scanning electron microscopy. Clinical
      studies should be conducted to investigate the in vivo activity of rokitamycin,
      as an agent to be used in the combination therapies against H. pylori.

PMID- 8981183
TI  - Production of sodium azide inactivating substance by resistant mutants of
      Salmonella typhimurium and other bacteria.
AB  - We have found that azide-resistant mutants of Salmonella typhimurium and of other
      bacteria studied produce a substance which inactivates the azide. The production
      of this substance was proved by the demonstration of a satellite growth of azide
      sensitive cells around colonies of azide-resistant mutants and by testing azide
      inactivating properties of culture filtrates of the azide-resistant strains. The
      same substance was found to be present in lower concentrations in culture
      filtrates of wild-type sensitive strains. In both cultures of sensitive strains,
      it was apparently produced by the resistant mutants and not by the sensitive
      cells. The substance does not pass across a dialysis membrane and is heat stable.
      It has a high molecular weight but is not a protein.

PMID- 8981184
TI  - Interaction of Candida albicans, macrophages and fluconazole: in vitro and ex
      vivo observations.
AB  - In recent years, medical interest in evaluating the interaction among mycetes,
      phagocytes, and antimycotic drugs has increased notably due to higher incidences
      of fungal infections in immunocompromised subjects and to the long-term therapy
      they require. In this study the in vitro and ex vivo interaction of fluconazole,
      at plasma concentrations, with mouse macrophages was evaluated in the presence of
      different inocula of Candida albicans. The results showed that fluconazole did
      not interfere negatively with phagocyte functions; conversely, according to
      different experimental conditions, it was able to increase both phagocytosis and
      intracellular killing of candida, probably exerting its action on the yeast
      rather than on the phagocyte. A higher enhancement of macrophage functions was
      observed in vitro when the drug was present in the medium with macrophages and
      candida in a 1:1 ratio.

PMID- 8981185
TI  - In vitro susceptibility of Trichosporon beigelii to antifungal agents.
AB  - The minimum inhibitory concentrations (MICs) and minimum fungicidal
      concentrations (MFCs) of amphotericin B, flucytosine, miconazole, fluconazole and
      itraconazole against 21 isolates of Trichosporon beigelii in RPMI-1640 medium
      were determined using National Committee for Clinical Laboratory Standards
      (NCCLS) methodology in microdilution method. Most isolates were sensitive to
      miconazole (MIC90 0.78 microgram/ml), fluconazole (MIC90 6.25 micrograms/ml), and
      itraconazole (MIC90 0.19 microgram/ml), with the former being the most active
      agent tested (MFC90 3.12 mu/ml). Although amphotericin B inhibited most strains
      (MIC range, 0.78-3.12 micrograms/ml), poor fungicidal activity was observed (MFC
      range, 1.56-12.5 micrograms/ml) showing a pattern of relative resistance in
      vitro. Flucytosine showed generally poor activity against most isolates tested.
      These in vitro findings confirm the resistance of T.beigelii to amphotericin B
      and suggest that azoles may be an alternative to the former for the treatment of
      disseminated trichosporonosis. However, in vivo studies would better validate
      these in vitro findings.

PMID- 8981186
TI  - Effects of FK-506 on the course of murine salmonellosis.
AB  - Bacterial infections are a major threat to immunocompromised patients. Therefore,
      the effect of immunosuppression with cyclosporin A and FK-506 on the course of
      murine salmonellosis was tested. Treatment of mice with both substances reduced
      the amount of circulating CD4+ T-cells and CD8+ T-cells in uninfected and
      infected mice. The substances effectively suppressed the proliferation of spleen
      cells of treated mice upon activation with concanavalin A (ConA) and upon
      activation by mouse peritoneal macrophages infected with live salmonellae, but
      left the response to lipopolysaccharide (LPS) unaltered. In particular, treatment
      of mice with nontoxic doses led to an increase in Salmonella typhimurium counts
      in the organs of primarily infected mice from day 14 onward, but not in the early
      phase of infection. In mice treated during secondary infection with S.
      typhimurium the bacterial counts in the organs were increased from day 3 of
      infection onward. We conclude that both substances aggravate murine
      salmonellosis, most likely by inhibition of T-cell function. Patients receiving
      FK-506 might also be, therefore, at risk of salmonella infection.

PMID- 8981187
TI  - Efficacy and safety of once-daily amikacin in combination with ceftazidime in
      critically ill adults with severe gram-negative infections.
AB  - Forty critically ill adult patients with severe Gram-negative infection were
      treated with once-daily amikacin combined with ceftazidime. The mean age was 56.6
      +/- 19 years and mean APACHE II score was 22.7 +/- 6.6. Forty percent of patients
      required mechanical ventilation. The mean creatinine clearance at onset of
      therapy was 59.4 +/- 28 ml/min. All bacterial isolates were sensitive to
      amikacin. Fixed doses of amikacin 15 mg/kg, 12 mg/kg, and 8 mg/kg body weight
      were given once daily to patients with estimated creatinine clearance of > 80
      ml/min., 50-80 ml/min., and < 50 ml/min, respectively. Forty-two causative gram
      negative bacteria were isolated from 40 patients. The most common bacteria were
      Pseudomonas aeruginosa (18), and Escherichia coli (10). Overall clinical success
      and bacteriological eradication occurred in 85% and 87.5% of patients; 78.9% and
      79% of patients with hospital-acquired infections; 90.5% and 95.2% of patients
      with community-acquired infections; and 62.5% and 81.3% of patients requiring
      mechanical ventilation, respectively. Therapeutic failure was documented in 15%
      of patients. Death due to infection was scored in two patients. The remaining
      were all due to persistence of the initial causative bacteria in patients with
      hospital-acquired infections. Persistence was documented with Ps. aeruginosa (2),
      Serratia spp. (1), and Acinetobacter spp. (1). Overall mortality occurred in
      22.5% patients. Death unrelated to infection occurred in 7 patients. There was no
      clinical evidence of ototoxicity in any of our patients, however, nephrotoxicity
      was documented in 5%. In conclusion, once-daily amikacin combined with
      ceftazidime is practical, efficacious and probably safe in critically ill
      infected patients.

PMID- 8981188
TI  - Development and partial characterization of a human T-lymphoblastic leukemic
      (CCRF-CEM) cell line resistant to etoposide. Analysis of possible circumventing
      approaches.
AB  - We have selected an etoposide-resistant variant (CCRF-CEM/VP-16) of the human T
      lymphoblastic CCRF-CEM leukemia for study. Resistance to the topoisomerase II
      (topo II) inhibitor was about 11-fold and stable. Other data revealed that the
      new cell line had acquired an atypical, non-P-glycoprotein overexpressing
      multidrug resistant (MDR) phenotype with cross-resistance to other topo II
      inhibitors (amsacrine, doxorubicin, and mitoxantrone) and to glucocorticoids, but
      not to novobiocin, ICRF-187, vincristine or cisplatin. In a first instance, we
      assumed that altered drug-topo II interactions, based on quantitative and/or
      qualitative modifications of the enzyme, are a cause of resistance in the cell
      line. We tried to modify the drug sensitivity of the cells by means of various
      agents and cytokines. Positive results were obtained with verapamil and, to a
      lesser extent, cyclosporin A, but they were not specific for the drug resistant
      variant and occurred in the parental CCRF-CEM as well. Other attempts with
      buthionine sulfoximine, novobiocin, pentoxifylline, interleukin-1, interferon
      alpha, retinoic acid, TNF-alpha, bryostatin 1 or phorbol myristate acetate were
      substantially unsuccessful, thus confirming the difficulty of pharmacologically
      overcoming atypical MDR. More encouragingly, however, CCRF-CEM/VP-16 cells
      exhibited hypersensitivity to other agents, including actinomycin D and taxol.

PMID- 8981189
TI  - Methotrexate serum concentration and histological response to multiagent primary
      chemotherapy for osteosarcoma of the limbs.
AB  - The authors investigated the influence of methotrexate (MTX) serum concentration
      on (histologically evaluated) tumor necrosis, induced by a primary multiagent
      chemotherapy, including MTX, for osteosarcoma. MTX serum peaks in 151 patients,
      preoperatively treated with MTX (8-12g/m2), cisplatin (120mg/m2) and Adriamycin
      (60mg/m2), were analyzed. Significantly (p < 0.01) higher serum MTX mean peaks
      were observed in patients with complete tumor necrosis (MTX 773.8 mumol/l)
      compared to patients with 90-99% tumor necrosis (639.8 mumol/l), 50-89% tumor
      necrosis (649.1 mumol/l) or less than 50% tumor necrosis (610 mumol/l). Complete
      tumor necrosis was observed in 9% of patients with MTX peaks of less than 600
      mumol/l, in 27% of patients with serum MTX peaks between 600 and 699 mumol/l and
      in 37% of those with MTX peaks ranging from 700 to 799 mumol/l. Higher MTX peaks
      (800-899, 900-999, > 1000 mumol/l) were not associated with a further increase of
      cases with complete tumor necrosis. 40% of patients with an MTX peak greater than
      700 mumol/l had complete tumor necrosis, compared to 15.5% of patients who did
      not reach this value (p < 0.002). At a multivariant analysis including age, sex,
      tumor site and volume, pretreatment serum alkaline phosphatase and lactic
      dehydrogenase levels, MTX peaks of 700 mumol/l and, less significantly, the
      histologic type (telangiectatic osteosarcoma), were independent factors
      influencing tumor necrosis. The authors conclude that MTX serum peaks
      significantly influence chemotherapy-induced tumor necrosis in osteosarcoma. In a
      primary treatment consisting of cisplatin, Adriamycin and MTX, complete tumor
      necrosis can be obtained in 40% of patients with MTX peak concentrations > or =
      700 mumol/l.

PMID- 8981190
TI  - Deadly sins, continued: treating patients with addictions.

PMID- 8981191
TI  - Putting advance-care planning into action.

PMID- 8981192
TI  - Death with Kantian dignity.

PMID- 8981193
TI  - Professional healthcare workers' attitudes toward treating patients with
      multidrug-resistant tuberculosis.

PMID- 8981194
TI  - Women and health research: working for change.

PMID- 8981195
TI  - The interrelationship of ethical issues in the transition from old paradigms to
      new technologies.

PMID- 8981196
TI  - Ethical issues in the development and use of guidelines for clinical practice.
AB  - In order to serve the purposes expected of them, practice guidelines must be more
      than summaries of available research; they must also challenge the values that
      are implicit in the way practice questions have been framed and outcomes have
      been chosen. The IOM has defined desirable attributes of practice guidelines,
      focused on the characteristics of measurement and implementation. It is also
      desirable for guidelines to meet certain ethical criteria.

PMID- 8981197
TI  - Should a patient who attempted suicide receive a liver transplant?

PMID- 8981198
TI  - Anubis and the feather of truth: judging transplant candidates who engage in self
      damaging behavior.

PMID- 8981199
TI  - Exclusionary criteria and suicidal behavior: comment on "should a patient who
      attempted suicide receive a liver transplant"?

PMID- 8981201
TI  - Clonal deletion as a mechanism of transplantation tolerance.

PMID- 8981202
TI  - Effect of pentoxifylline on renal toxicity of cyclosporine: results of a clinical
      trial after heart transplantation.
AB  - BACKGROUND: Pentoxifylline was suggested to prevent the renal release of
      endothelin caused by cyclosporine. METHODS: We studied the renal-sparing effect
      of pentoxifylline in 44 patients who underwent heart transplantation between 1991
      and 1994 and were randomized to a group treated with pentoxifylline (400 mg three
      times daily) or to a control group. All patients were treated according to the
      same immunosuppression protocol, including induction with perioperative rabbit
      anti-thymocyte antibody and maintenance with azathioprine, cyclosporine, and
      prednisone. Five patients withdrew voluntarily because of lack of compliance, and
      five patients died during the first month of the study. RESULTS: There was no
      difference between the two groups in regard to age, sex, initial cardiopathy, the
      number of acute rejections, and the number of infection episodes. Urinary
      clearance of creatinine averaged 1.1 +/- 0.1 ml/sec, 1.3 +/- 0.1 ml/sec, and 1.3
      +/- 0.1 ml/sec in the control patients (n = 16) and 1.2 +/- 0.1 ml/sec, 1.4 +/-
      0.1 ml/sec, and 1.3 ml/sec in patients treated with pentoxifylline (n = 18) at
      initiation, 12 months, and 24 months of the study (p > 0.05), respectively. At
      these three times, the serum creatinine levels averaged 106 +/- 4 mmol/L, 119 +/-
      4 mmol/L, and 126 +/- 5 mmol/L in the control group and 94 +/- 4 mmol/L, 114 +/-
      4 mmol/L, and 127 +/- 5 mmol/L in patients treated with pentoxifylline,
      respectively (p > 0.05). Trough levels of cyclosporine throughout the study
      period averaged 212 +/- 8 mmol/L and 206 +/- 8 mmol/L in the control and treated
      groups, respectively (p > 0.05). Endothelin blood levels averaged 0.4 +/- 0.2
      pg/ml for nine control patients and 0.4 +/- 0.1 pg/ml for a group of 10 patients
      treated with pentoxifylline (p > 0.05). CONCLUSIONS: Pentoxifylline in
      association with cyclosporine did not result in a significant improvement in
      renal function during the first 2 years after heart transplantation.

PMID- 8981203
TI  - The intragraft cytokine mRNA pattern reflects the efficacy of steroid
      antirejection therapy.
AB  - BACKGROUND: We studied the effect of antirejection therapy on intragraft cytokine
      mRNA expression. METHODS: Therapy consisted of three doses of 1 gm of intravenous
      methylprednisolone. We determined its effect on intragraft mRNA expression of
      immunoregulatory (interleukin-2, interleukin-4) and inflammatory cytokines
      (interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha), and the high
      affinity interleukin-2 receptor (p55 chain) in endomyocardial biopsy specimens
      from cardiac allograft recipients. RESULTS: By reverse-transcriptase polymerase
      chain reaction methods, we detected mRNA transcription for interleukin-2 in 56%
      of the pretreatment endomyocardial biopsy specimens (n = 16), for interleukin-4
      in 31%, and for interleukin-6 in 56% of the specimens, and interleukin-2
      receptor, interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha were
      constitutively expressed. Individual cytokine mRNA profiles were not helpful in
      differentiating between rejections that proved to be methylprednisolone resistant
      (n = 9) or methylprednisolone sensitive (n = 7). After successful antirejection
      therapy, the overall intragraft mRNA expression was downregulated. None of the
      posttreatment endomyocardial biopsy specimens taken from six patients with
      methylprednisolone-sensitive rejections expressed the interleukin-2 gene, in
      contrast to 88% of the endomyocardial biopsy specimens obtained from eight
      patients with methylprednisolone-resistant rejections (p = 0.005). Moreover,
      intragraft interleukin-4 and interleukin-6 mRNA transcripts were hardly
      detectable (both 17%) in methylprednisolone-reversible rejections, but in ongoing
      rejections interleukin-4 mRNA expression was found in 62% (p = 0.14), and
      interleukin-6 was found in 88% of the endomyocardial biopsy specimens (p = 0.03).
      Semiquantitative analysis showed that the intragraft interleukin-2 receptor,
      interleukin-1 beta, and tumor necrosis factor-alpha mRNA levels were lower in
      posttreatment endomyocardial biopsy specimens from methylprednisolone-reversible
      rejections than in endomyocardial biopsy specimens from methylprednisolone
      irreversible rejections (p = 0.03). CONCLUSIONS: Our data suggest that the
      efficacy of antirejection therapy with methylprednisolone is reflected in
      intragraft cytokine mRNA profiles.

PMID- 8981204
TI  - RANTES chemokine expression in transplant-associated accelerated atherosclerosis.
AB  - BACKGROUND: The pathogenesis of transplantation-associated accelerated
      atherosclerosis is poorly understood, but it is likely to be an alloimmune
      response involving infiltration of the vessel wall by T lymphocytes and monocytes
      leading to smooth muscle cell proliferation and extracellular matrix deposition.
      RANTES is a chemokine that selectively chemoattracts T lymphocytes, NK cells,
      monocytes, and eosinophils. The expression of RANTES in accelerated
      atherosclerosis was investigated by in situ hybridization and
      immunohistochemistry. METHODS: Coronary arteries from six patients undergoing
      accelerated atherosclerosis were obtained at the time of retransplantation.
      Normal coronary arteries from two patients with idiopathic dilated cardiomyopathy
      were used as controls. Messenger RNA for RANTES was localized with digoxigenin
      labeled complementary DNA probes. RANTES protein was detected by use of a
      monoclonal antibody and a three-step horseradish peroxidase method. RESULTS:
      RANTES mRNA and protein were detected in the lymphocytes, macrophages,
      myofibroblasts, and endothelial cells of arteries undergoing accelerated
      atherosclerosis but not in normal coronary arteries. CONCLUSIONS: In view of its
      in vitro biologic activity and in vivo expression pattern, RANTES may be a
      pivotal mediator of the cellular infiltrate seen in graft atherosclerosis. This
      information may help in the design of novel diagnostic and therapeutic approaches
      to this increasingly important disease process.

PMID- 8981205
TI  - Risk factors for the development of obliterative bronchiolitis after lung
      transplantation.
AB  - BACKGROUND: Acute rejection has emerged as an important risk factor for
      obliterative bronchiolitis after lung transplantation. We performed a
      multivariate analysis to assess the impact of additional variables. METHODS:
      Seventy-four recipients (48 heart-lung, 18 single-lung, and 8 bilateral-lung
      recipients) who survived longer than 90 days and underwent transplantation more
      than 15 months before data analysis were included in this study. Several
      variables were entered into a Cox regression analysis to determine their
      association with the development of bronchiolitis obliterans syndrome. RESULTS:
      Bronchiolitis obliterans syndrome developed in 48 (65%) of 74 patients.
      Significant correlations were detected for acute rejection score, defined as the
      sum of pathologic grades of each separate acute rejection episode (p = 0.0004,
      likelihood ratio test value = 12.4) and for lymphocytic bronchiolitis (p = 0.03).
      In a bivariate model, episodes of organizing pneumonia and bacterial or fungal
      pneumonia significantly increased the likelihood ratio test value of the acute
      rejection score. The addition of the cytomegalovirus infection score, reflecting
      the frequency and severity of infection, to the combination of the acute
      rejection score and episodes of bacterial or fungal pneumonia resulted in a
      further significant increase in the likelihood ratio test value. Significant risk
      factors for moderate to severe stages of airflow limitation were at least one
      episode of acute rejection of grade > or = 2, younger recipient age, and any
      acute rejection episode 180 days or longer after transplantation. CONCLUSIONS:
      Increasing frequency and severity of acute rejection episodes are strongly
      associated with the development of bronchiolitis obliterans syndrome. Lymphocytic
      bronchiolitis appeared to be significant by univariate analysis, but in a two
      risk factor model, it did not augment the influence of acute rejection.
      Organizing pneumonia, bacterial or fungal pneumonia, and increasing severity and
      frequency of cytomegalovirus infections potentiate the effect of acute rejection.
      Late episodes of acute rejection and younger recipient age increase the risk for
      development of advanced disease.

PMID- 8981206
TI  - Influence of human leukocyte antigen matching on long-term outcome after lung
      transplantation.
AB  - BACKGROUND AND METHODS: The importance of human leukocyte antigen matching for
      long-term outcome after lung transplantation is uncertain. We therefore analyzed
      retrospectively 78 consecutive primary, isolated lung transplantations (37
      female, 41 male; 40 single, 38 bilateral) performed between October 1989 and
      October 1995 for which human leukocyte antigen typing of both donor and recipient
      was available. The follow-up ranged from 1 day to 60.3 months. Graft failure,
      defined as retransplantation or patient death, served as end point. RESULTS:
      Graft survival was significantly better with one mismatch at the B locus than
      with two mismatches (p = 0.046): 67% versus 51% and 61% versus 25% graft survival
      at 12 and 36 months, respectively. For the B and DR loci combined, a marked
      matching effect was also observed (p = 0.21 for zero to two mismatches versus
      three to four mismatches: 81% versus 62% and 51% versus 29% graft survival at 12
      and 36 months, respectively. The sum of mismatches at the A, B, C, and DR loci
      combined showed a similar effect (p = 0.17 for zero to four mismatches versus
      five to eight mismatches: 83% versus 62% and 58% versus 29% graft survival at 12
      and 36 months, respectively. Although no clear effect could be shown for the
      isolated DR locus, the outcome for the three patients with zero mismatches was
      notably good: one patient is alive at 27 months, two died 37 and 48 months after
      transplantation. The number of acute rejection episodes showed a clear but
      insignificant correlation to the number of mismatches. A similar trend was
      observed for the incidence of bronchiolitis obliterans syndrome. CONCLUSIONS: In
      summary, a strong influence of human leukocyte antigen matching on the long-term
      outcome after lung transplantation is suggested by our results. A clear trend
      toward improved graft survival with better human leukocyte antigen matching was
      observed, with the most significant effect occurring at the B locus.

PMID- 8981207
TI  - Humoral (antibody-mediated) rejection in lung transplantation.
AB  - To confirm the existence and characterize the pathologic features of humoral
      (antibody-mediated) lung rejection, we prospectively studied 55 lung transplant
      recipients (24 male [44%] and 31 female [56%], age range 14 to 69 years [mean
      45]). The time between transplantation and biopsy ranged from 2 to 1546 days
      (mean 274). We performed direct immunofluorescence with C3, immunoglobulin M, and
      immunoglobulin G antibodies on frozen sections of 106 transbronchial biopsies and
      one wedge biopsy and compared the results with 13 explanted lungs, one donor
      lung, and two controls. The histologic diagnoses of these 107 biopsies included
      acute cellular rejection (62, 58% [minimal 23, mild 33, moderate 5, and severe
      1]), chronic rejection (eight, 7%), chronic vascular rejection (two, 2%), acute
      vasculitis (five, 5%), cytomegalovirus pneumonitis (two, 2%), acute pneumonia
      (two, 2%), acute organizing pneumonia (two, 2%), diffuse alveolar damage (one,
      1%), no evidence of rejection or infection (30, 28%), lipoid pneumonia (one, 1%),
      and inadequate for histologic diagnosis (one, 1%). Eighty-nine of 106 (84%)
      transbronchial biopsies, the wedge biopsy, and control lungs were satisfactory
      for direct immunofluorescence, because each contained alveolate lung parenchyma
      and arterioles or venules. There was no demonstrable immunofluorescence in the
      wall of the blood vessels or in the lung parenchyma in any case. We conclude that
      (1) transbronchial biopsies and wedge biopsies provide adequate material to
      evaluate humoral rejection, and (2) in spite of the large population studied, the
      satisfactory material obtained, and the wide range of histologic diagnoses, we
      could not demonstrate the occurrence of humoral rejection in the lung.

PMID- 8981208
TI  - Prominence of apolipoproteins B, (a), and E in the intimae of coronary arteries
      in transplanted human hearts: geographic relationship to vessel wall
      proteoglycans.
AB  - BACKGROUND: Transplant arteriopathy (TA) is characterized by vessel wall
      thickening with prominent glycosaminoglycan and lipid deposits. In this light, we
      have recently demonstrated the distribution of proteoglycans in allograft
      coronary arteries. The aim of this study is to examine the distribution of
      apolipoproteins within allograft coronary arteries and to investigate their
      localization in relation to proteoglycans. METHOD: Particular transverse sections
      of left and right epicardial coronary arteries from 46 human cardiac allografts,
      11 normal hearts, and 11 hearts with native atherosclerosis were stained
      immunohistochemically for apolipoprotein B, apolipoprotein (a) (apo[a]),
      apolipoprotein E (apoE), biglycan, decorin, and versican by use of an automated
      immunostainer. RESULTS: Apo(a) and apoE immunopositivity in TA was much more
      intense than that in native atherosclerosis, whereas the reverse was true for
      apoB. Prominent apoE deposits were evident circumferentially in endothelia and
      extracellularly in superficial intima of mildly diseased TA, as well as in deeper
      intima of severely diseased TA. Apo(a) had a staining pattern very similar to
      apoE except for a patchy deposition also seen in TA media. The intimal areas
      staining prominently with apoE or apo(a) in TA arteries corresponded very closely
      to the areas with proteoglycan deposits, especially versican. CONCLUSION: The
      distinctive patterns of apolipoprotein accumulation in TA and native
      atherosclefosis appear to reflect different pathogenetic processes in the two
      conditions. The colocalization of proteoglycans and apolipoproteins in TA intima
      supports the hypothesis that interactions between proteoglycans and
      apolipoproteins influence lipid retention and overload in allograft coronary
      arteries.

PMID- 8981209
TI  - Biglycan, decorin, and versican protein expression patterns in coronary
      arteriopathy of human cardiac allograft: distinctness as compared to native
      atherosclerosis.
AB  - BACKGROUND: Histochemical staining has demonstrated previously dramatic deposits
      of glycosaminoglycans associated with prominent lipid accumulations in thickened
      vessel walls of allograft coronary arteries. In this study, we characterized the
      amount, distribution, and types of proteoglycan in the walls of coronary arteries
      from human cardiac allografts and from native atherosclerotic (NA) controls as
      part of a strategy to understand the pathogenesis of transplant arteriopathy
      (TA). METHOD: We used polyclonal rabbit antibodies against human biglycan,
      decorin, and versican localize the proteoglycan molecules in standardized
      transverse sections of the proximal left anterior descending and right coronary
      arteries. Slides were scored in a blinded fashion for intensity of proteoglycan
      staining (0 to 6+) and for localization in the vessel walls. RESULTS: Unique
      patterns of proteoglycan distribution were present in TA and NA. Biglycan was
      particularly prominent in intima and evolving atheromata in severely diseased TA
      coronary arteries, but not in NA. Decorin was present mainly in adventitia of all
      vessels and in the intima of NA. Prominent versican accumulation occurred in
      intima and media of TA coronaries, associated with smooth muscle cells and foam
      cells. There was a reciprocal pattern of biglycan and decorin staining. Versican
      colocalized with biglycan. Intimal biglycan and versican deposits were positively
      correlated to the extent of luminal narrowing in TA. CONCLUSION: The distinctive
      staining patterns for biglycan, decorin and versican in both native and allograft
      disease indicate that the synthesis and distribution of these proteoglycans are
      regulated by different local mechanisms in different atheromatous diseases.

PMID- 8981210
TI  - L-arginine prevents heart transplant arteriosclerosis by modulating the vascular
      cell proliferative response to insulin-like growth factor-I and interleukin-6.
AB  - BACKGROUND: L-arginine, a nitric oxide precursor, inhibits myointimal hyperplasia
      induced by balloon injury in native vessels. No studies are published on L
      arginine effects on transplant arteriosclerosis. Insulin-like growth factor-I and
      interleukin-6 are mitogenic for smooth muscle cells and are involved in the cell
      mediated and humoral immune response. METHODS: New Zealand White rabbits received
      cardiac allografts from Dutch Belted rabbits. All animals were fed a 0.5%
      cholesterol diet and received drinking water with (eight pairs) or without (eight
      pairs) L-arginine (2.5%) from day 7 to until they were killed at day 42. The
      recipients received cyclosporine A 10 mg/kg/day from transplantation until the
      time they were killed. RESULTS: Dietary L-arginine reduces myointimal hyperplasia
      in allograft coronary arteries from 44% +/- 4% in the non-L-arginine group to 16%
      +/- 2% (p < 0.002). The L-arginine significantly inhibits graft vascular cell
      proliferation induced by (1) insulin-like growth factor-I, from 328% +/- 66% to
      154% +/- 28% (p < 0.05), (2) interleukin-6, from 376% +/- 97% to 138% +/- 30% (p
      < 0.05) and (3) the combination of insulin-like growth factor-I and interleukin-6
      from 710% +/- 201% to 226% +/- 72% (p < 0.05). In recipient native aorta explants
      L-arginine also abolishes vascular cell proliferation stimulated by insulin-like
      growth factor-I and interleukin-6. The rejection grading is similar in the L
      arginine (2.9 +/- 0.1) and control groups (2.7 +/- 0.1). Class II major
      histocompatibility antigen expression, T-lymphocyte, and macrophage infiltration
      in the cardiac allograft are unaffected by L-arginine. However, the diet
      significantly increased plasma nitric oxide from 15.4 +/- 2.3 to 45.1 +/- 11
      mumol (p < 0.05). CONCLUSIONS: Dietary L-arginine attenuates transplant
      arteriosclerosis in vivo without affecting rejection. The protective effect seen
      in these experiments may relate to the generation of sufficient nitric oxide to
      prevent smooth muscle cell response to mitogens like insulin-like growth factor-I
      and interleukin-6.

PMID- 8981212
TI  - Should cryptogenic organizing pneumonia be included in the classification of
      pulmonary allograft rejection?

PMID- 8981211
TI  - Ischemic preconditioning enhances donor lung preservation in the rat.
AB  - BACKGROUND: Ischemic preconditioning achieved by brief periods of ischemia and
      reperfusion before a prolonged period of ischemia can significantly reduce the
      extent of cardiac damage in many mammalian species and human beings. In this
      study we used a rat model of single lung transplantation to show that ischemic
      preconditioning also occurs in the lung. METHODS: Rats randomly selected for
      ischemic preconditioning had their left main bronchus and pulmonary artery
      occluded for 5 minutes, followed by 10 minutes of reperfusion and ventilation.
      Lungs of control rats were ventilated for 15 minutes. The lungs were perfused
      with University of Wisconsin solution, then heart and lungs were excised en bloc
      and stored in University of Wisconsin solution at 0 degree C for 6 or 12 hours.
      After left pneumonectomy, the left lung of the donor was then implanted into the
      recipient via left thoracotomy. After 1 hour of ventilation and reperfusion, a
      right pneumonectomy was performed making the animal completely dependent on the
      transplanted lung. Samples of arterial blood from the left ventricle were then
      taken for arterial oxygen tension and arterial carbon dioxide tension
      determination. Water contents of the donor lungs were measured before and after
      reperfusion. Thiobarbituric acid reactive substances were measured in the right
      donor lung after storage. RESULTS: Lungs transplanted after 12 hours of storage
      had profoundly impaired gas exchange (arterial oxygen tension = 34 +/- 5;
      arterial carbon dioxide tension = 69 +/- 7 mm Hg) compared with the normal levels
      in the 6-hour storage group (arterial oxygen tension = 308 +/- 22; arterial
      carbon dioxide tension = 17 +/- 1 mm Hg). Ischemic preconditioning significantly
      improved gas exchange in the 12-hour storage group (arterial oxygen tension = 83
      +/- 11; arterial carbon dioxide tension = 40 +/- 4 mm Hg). Ischemic
      preconditioning also significantly decreased thiobarbituric acid reactive
      substances formation at both 6- and 12-hour storage. CONCLUSIONS: These results
      show that the phenomenon of ischemic preconditioning occurs in the lung and that
      it may reduce injury to the donor lung during prolonged cold ischemic storage.

PMID- 8981213
TI  - Intraocular lens implants: a biocompatibility review.
AB  - The natural aging process of the eye inevitably leads to the formation of a
      cataract, resulting in an increasing loss of vision. A cataract is the clouding
      of the natural lens in the eye and represents a major physical impairment. Modern
      surgical techniques allow for removal of the clouded lens and replacement with a
      prosthetic intraocular lens. This article reviews the intraocular tissue response
      to the implant, which frequently leads to postoperative complications for the
      patient.

PMID- 8981214
TI  - L-arginine supplementation improves venous endothelial cell but not smooth muscle
      cell dysfunction induced by prolonged diet-induced hypercholesterolemia.
AB  - Hypercholesterolemia induces venous vasomotor dysfunction. This study examines
      the endothelial and smooth muscle cell vasoreactivity of external jugular veins
      from rabbits fed either a normal or a 1% cholesterol diet for 8 weeks with and
      without L-arginine supplementation (2 g/kg day-1 orally for the last 5 weeks).
      Isometric tension studies were performed on harvested jugular veins.
      Concentrations of serum cholesterol were 20-fold higher than controls and serum L
      arginine twofold higher than untreated animals. Hypercholesterolemia induced
      hypersensitivity to norepinephrine (p < .05), bradykinin (p < .05), and histamine
      (p < .05) with a contractile response to serotonin compared to controls. L
      Arginine supplementation decreased bradykinin hypersensitivity but had no effect
      on the changes in norepinephrine serotonin and histamine responses compared to
      controls. Hypercholesterolemia interfered with relaxation induced by
      acetylcholine but with L-arginine, normal acetylcholine-induced, endothelium
      dependent relaxation returned (54 +/- 10%, compared to 40 +/- 14% in control
      veins; p > .05). Non-endothelium-dependent relaxation to sodium nitroprusside of
      precontracted veins was unaffected by the presence of high cholesterol
      concentrations. This study suggests that L-arginine therapy may ameliorate
      hypercholesterolemia-induced functional abnormalities in endothelial cells.

PMID- 8981215
TI  - Kinetics of altered angiotensin II responses in experimental vein grafts.
AB  - Following vein grafting, responses in the arterial vein bypass grafts to
      angiotensin II, a known mitogen, increase. It is not known when these changes
      occur or whether these changes are due to alterations in endothelial cell
      function, excision/implantation of the vessel, or exposure to arterial
      hemodynamics. Two studies were designed to examine these questions. New Zealand
      White rabbits underwent excision of the external jugular vein, common carotid
      artery, an external jugular veno-venous bypass (VVG), or a common carotid veno
      arterial bypass (VAG). Half the jugular veins and carotid arteries were
      mechanically denuded of their endothelium. All vein grafts were harvested at 28
      days. A set of VAG was also harvested at 1, 3, 7, and 14 days. Isometric tension
      studies to angiotensin II (10(-10) to 10(-4) M) were performed on rings from each
      jugular vein, carotid artery, and vein graft. Jugular veins had a triphasic
      response to angiotensin II. Deendothelialized jugular veins had a triphasic
      response with an increased first phase and a much reduced second phase. Carotid
      arteries (6.87 +/- 0.18 and 6.15 +/- 0.18; with and without endothelium; means +/
      SEM, -log10[EC50); p < .05), VVG (6.69 +/- 0.15), and VAG (7.42 +/- 0.29; p <
      .05 compared to VVG) showed a monophasic response to angiotensin II at 28 days.
      This monophasic response in VAG to angiotensin II was recordable at 7 days
      postoperatively and there was no further change in its sensitivity between 14 and
      28 days. These results suggest that the induction of altered angiotensin II
      responses is dependent on exposure to the arterial circulation, that alterations
      in VAG responses occur within the first 7 days of vein grafting, and that VAG at
      28 days become more sensitive to angiotensin II than the carotid vessels into
      which they are placed. These changes in smooth muscle cell sensitivity to a known
      smooth muscle cell mitogen (angiotensin II) may contribute to the development of
      intimal hyperplasia in the veno-arterial graft.

PMID- 8981217
TI  - Effect of the endothelin receptor antagonist bosentan on postischemic oxygen
      supply of the liver.
AB  - Endothelin evokes strong and longlasting constriction of postischemic sinusoids,
      leading to microcirculatory disturbances and local hypoxia, thereby causing liver
      damage. The aim of the study was to avoid the constrictive response of sinusoids
      by blocking endothelin receptors. In an in vivo ischemia-reperfusion model (21
      female Wistar rats, 250-300 g) with portal decompression by a splenocaval shunt,
      hepatic ischemia was induced for 30 min by cross clamping of the hepatoduodenal
      ligament. The endothelin receptor antagonist bosentan (10 mg/kg bw IV) was
      administered before ischemia. The effect of the receptor antagonist was assessed
      by serum levels of aspartate aminotransferase (ASAT) and alanine aminotransferase
      (ALAT) that were determined prior to ischemia, 2 and 6 h postoperatively. The
      local tissue pO2 was measured prior to inducing ischemia, 30 and 60 min after
      reperfusion. Application of 10 mg/kg bw endothelin receptor antagonist (ERA)
      intravenously did not influence the systemic blood pressure. The postischemic
      increase in serum ASAT and ALAT levels was diminished after receptor antagonist
      treatment (ASAT: p < .05). Local postischemic hepatic tissue pO2 was
      significantly decreased to 45% of basal values after 30 min and to 54.8% after 60
      min of reperfusion (p < .05). Application of ERA results in a significant
      increase in local tissue pO2 to 110.9% of basal values after 30 min and to 90.7%
      after 60 min of reperfusion (p < .05). These data indicate that the endothelin
      receptor antagonist treatment results in a prevention of postischemic sinusoidal
      constriction avoiding hypoxia and leading to improved hepatocellular recovery.

PMID- 8981216
TI  - Peritracheal fibrosis induced by sclerosing agents: a putative treatment for
      tracheomalacia.
AB  - Tracheomalacia is a congenital or acquired deficiency of the cartilages of the
      trachea. Treatment procedures include formation of external support by insertion
      of cartilage; bone for foreign material into the peritracheal tissue. A
      sclerosing agent, sodium morrhuate, was injected in the peritracheal tissue,
      blindly or after skin incision and subcutaneous tissue. In both groups
      peritracheal granulation tissue and inflammation evolved into peritracheal
      fibrosis surrounding the cartilage at the site of injection. The reaction was
      more pronounced following incision of the skin. No fibrosis was observed in a
      control group following hypertonic saline injection. The results suggest that
      injection of sclerosing agents might be considered as a conservative mode of
      treatment in tracheomalacia, by producing peritracheal fibrosis as external
      support.

PMID- 8981218
TI  - Alterations of angiotensin II Receptor levels in sutured wounds in rat skin.
AB  - Angiotensin II receptor levels have been shown to vary with postoperative time in
      tissue harvested from full-thickness dermal excisional wounds on adult rats. This
      study examined the expression of AII receptors in a sutured wound model. Two full
      thickness incisional wounds were made in the dorsal skin of adult Sprague-Dawley
      rats and sutured immediately under general anesthesia. The wound tissues were
      harvested at 0, 0.5, 1, 2, 4, 24 h and on days 2, 3, 4, 5, 7, and 10 after the
      wounding. The levels of 125I-Sar1.Ile8-AII bound to membrane preparations of the
      wound tissues decreased at early time points (from 0.5 to 4 h), increased from
      day 1 to day 7, and returned to nonsurgical levels by day 10. Competitive binding
      studies showed that the receptors were predominantly of the AT1 receptor subtype.
      These results suggest that an immediate and transient reduction in AII receptor
      expression occurred after wounding, followed by an increase in the number of AII
      receptors that was maintained for 5 to 7 days postoperatively. Because these data
      are consistent with those observed after excisional wounding, temporal changes in
      AII receptor expression may be integral to the process of wound healing.

PMID- 8981219
TI  - Evaluation of transit-time and electromagnetic flow measurement in a chronically
      instrumented nonhuman primate model.
AB  - The Physiology Research Branch at Brooks AFB conducts both human and nonhuman
      primate experiments to determine the effects of microgravity and hypergravity on
      the cardiovascular system and to identify the particular mechanisms that invoke
      these responses. Primary investigative efforts in our nonhuman primate model
      require the determination of total peripheral resistance, systemic arterial
      compliance, and pressure-volume loop characteristics. These calculations require
      beat-to-beat measurement of aortic flow. This study evaluated accuracy,
      linearity, biocompatability, and anatomical features of commercially available
      electromagnetic (EMF) and transit-time flow measurement techniques. Five rhesus
      monkeys were instrumented with either EMF (3 subjects) or transit-time (2
      subjects) flow sensors encircling the proximal ascending aorta. Cardiac outputs
      computed from these transducers taken over ranges of 0.5 to 2.0 L/min were
      compared to values obtained using thermodilution. In vivo experiments
      demonstrated that the EMF probe produced an average error of 15% (r = .896) and
      8.6% average linearity per reading, and the transit-time flow probe produced an
      average error of 6% (r = .955) and 5.3% average linearity per reading.
      Postoperative performance and biocompatability of the probes were maintained
      throughout the study. The transit-time sensors provided the advantages of greater
      accuracy, smaller size, and lighter weight than the EMF probes. In conclusion,
      the characteristic features and performance of the transit-time sensors were
      superior to those of the EMF sensors in this study.

PMID- 8981220
TI  - Evaluation of Ca-P coatings in animal experiments: importance of study design.
AB  - During the last decennium the research on oral implants has increased
      considerably. A lot of different implant materials and types have been tested,
      but differences in study design and evaluation criteria make comparison of the
      results difficult. The purpose of this paper is to discuss surgical, statistical,
      and histological methods for testing and evaluating the biocompatibility of oral
      implants. Many formulas are available for calculating the required group size.
      The paper describes how such calculations can be used for the evaluation of
      implants and reviews the preferred surgical techniques. The control of various
      external influences that can contribute to the variability in obtained data are
      discussed. After implantation, the implants with their surrounding tissues are
      retrieved and subjected to histological evaluation. Currently, because of
      technical limitations, light microscopical sectioning is still the preferred
      preparation technique. After sectioning, quantitative analysis has to be
      performed. The parameters that can be evaluated are described. Finally, the use
      and potential of the described techniques are demonstrated with two examples.

PMID- 8981221
TI  - Electrovesicogram in the neurogenic bladder.
AB  - The vesical electric activity was studied by electrovesicogram (EVG) in 24
      patients with spinal cord injury: 15 with upper (UMNL) and 9 with lower (LMNL)
      motor neuron lesion. Mean age was 48.3 years; 16 were men and 8 were women. Eight
      healthy volunteers acted as controls. Transcutaneous recording was done with both
      a full and empty urinary bladder. three electrodes were applied supra-pubically
      and one reference electrode was applied to the lower limb. The normal volunteers
      recorded regular triphasic pacesetter potentials (PPs), which were reproducible
      in the individual subject. The electrovesicographic pattern was similar in the
      full and empty bladder, except that the PPs of the latter had a lower amplitude.
      the patients with UMNL showed "dysrhythmic" pattern with irregular rhythm,
      amplitude, and frequency in both the full and empty urinary bladder. Patients
      with LMNL exhibited "silent" EVG. The results indicate that electrovesicography
      could be used as an investigative tool that may help in the diagnosis of such
      conditions. The technique is simple, easy, noninvasive, and without
      complications.

PMID- 8981222
TI  - A new experimental model for simultaneous evaluation of aortic and pulmonary
      allograft performance in a composite graft.
AB  - A model was developed in pigs for simultaneous evaluation of aortic and pulmonary
      allograft performance in a composite graft. The composite graft consisted of
      vascular prosthesis and aortic and pulmonary allografts. Following antibiotic
      preservation, it was anastomosed to the recipient's thoracic descending aorta by
      an extrapleural approach without using cardiopulmonary bypass. Aortic blood flow
      was completely diverted into the composite graft. All 12 recipient pigs recovered
      well, 4 of which were assigned for the initial study to design the suitable
      experimental schedule. Calcification readily occurred in the aortic allografts
      and aneurysmal dilatation without calcification developed in the pulmonary
      allografts. These morphological findings were consistent with those of previous
      reports. This model has several benefits. First, aortic and pulmonary allograft
      conduits can be implanted and evaluated simultaneously under the same conditions
      by making a composite graft. Second, the magnitude of the operation is minimum,
      and postoperative circulatory and respiratory management is uncomplicated. Third,
      wound infection rarely occurs, because the skin incision is made on the back.
      These preliminary studies suggest that this model will allow future study
      concerning aortic and pulmonary allograft conduits under different conditions.

PMID- 8981223
TI  - Sliding, absorbable, reinforced ring and an axially driven stent placement device
      for sutureless fibrin glue gastrointestinal anastomosis.
AB  - Reduced blood flow of from 43 to 71% has been reported in sutured and stapled
      anastomoses. The sutureless sliding, absorbable, intraluminal, nontoxic stent
      (SAINT)-fibrin glue anastomotic method, which clamps the stump margins between 2
      dissolving surfaces, includes only two stages of temporary compression (about 6
      min total using 4 IU/mL thrombin) during the glue application in order to promote
      vascularization. A SAINT placement device (SAINT-PD) was introduced to facilitate
      low rectal anastomoses. Morphohistologic results from limited trials using fibrin
      glue with an untied sutureless stapler technique and a prototype non-gear-driven
      SAINT-PD, neither having the two dissolvable clamping surfaces of the SAINT,
      showed a 29 and 25% incidence of intraluminal tissue ridges, respectively. Since
      these tissue ridges could result in subclinical dilatation or frank stenosis, and
      the more extensive SAINT trials had an 8% incidence of tissue ridges, redesign of
      the SAINT-PD was undertaken. Consequently, to improve the anastomotic quality of
      the SAINT-PD, the sliding absorbable reinforced ring (sucrose base) acting as the
      second dissolvable surface for the SAINT-PD and a new axially controlled geared
      SAINT-PD design are described.

PMID- 8981224
TI  - The role of phosphoinositide 3-kinase in insulin signalling.

PMID- 8981225
TI  - Effect of lymphocytes on hormonal secretion by autologous thyrocytes cultured in
      monolayers.
AB  - We studied the lymphocyte-induced alterations in hormonal metabolism and the
      production of tumour necrosis factor alpha (TNF-alpha) during coculture of
      thyrocytes and autologous lymphocytes from 20 patients with Graves' disease and
      from five normal subjects. Thyroglobulin (Tg) mRNA was assessed by slot-blot
      analysis under TSH stimulation. Tg, tri-iodothyronine (T3) and cAMP secretion in
      the presence of TSH were measured by RIA after 3 or 5 days of coculture. TNF
      alpha levels produced after 5 days incubation were also assayed in lymphocyte
      culture and coculture media. Lymphocytes isolated from peripheral blood (PBLs)
      altered the production of Tg, T3 and cAMP in autologous thyrocytes.
      Intrathyroidal lymphocytes (ITLs) decreased Tg and cAMP secretion but had no
      effect on T3 secretion. The reductions in Tg and cAMP levels obtained with
      mechanically isolated ITLs (M-ITLs) were generally higher than those obtained
      with ITLs isolated by dispase (D-ITLs). No difference was seen between Graves'
      disease and normal cocultures. PBLs secreted large concentrations of TNF-alpha,
      larger than those obtained with M-ITLs whereas D-ITLs produced low amounts of
      this cytokine. In coculture, TNF-alpha levels were lower than those observed in
      lymphocyte culture. Significant correlations were obtained between TNF-alpha
      levels and the decrease in Tg, T3 and cAMP concentrations. The percentage of T
      lymphocytes was higher in PBLs and D-ITLs than in M-ITLs. B lymphocytes levels
      were higher in ITLs, especially M-ITLs, than in PBLs. TNF-alpha production by B
      lymphocytes was maximal in M-ITLs. In conclusion, lymphocytes induced a decrease
      in hormonal thyroid metabolism when cocultured with autologous thyrocytes. These
      perturbations may be attributed, at least partly, to TNF-alpha secreted by
      lymphocytes. TNF-alpha interacts via the adenylate cyclase pathway of TSH signal
      transduction.

PMID- 8981226
TI  - The 5' flank of the rat estrogen receptor gene: structural characterization and
      evidence for tissue- and species-specific promoter utilization.
AB  - Published data on the rat estrogen receptor (rER) gene have so far provided
      evidence for only one promoter. In contrast, the human ER (hER) gene has been
      reported to be transcribed from three different promoters A, B and C. In order to
      facilitate a more in-depth analysis of the promoter organization in the rER gene
      4.5 kb of its 5' flanking region were isolated. Sequence analysis suggests that
      the rER gene is transcribed from a promoter homologous to promoter B in the hER
      gene. However, the region corresponding to the human promoter A is much more
      divergent between the species and rapid amplification of cDNA ends (RACE)-PCR as
      well as RT-PCR experiments support the notion that the rER gene does not contain
      a functional A promoter. Interestingly, a novel rER mRNA isoform containing a
      previously unknown 5' untranslated exon was isolated by RACE-PCR, suggesting the
      existence of a second, distal promoter in the rER gene. Our results show that
      this ER mRNA isoform C is the only one expressed in rat liver. It thus appears
      that the rER gene contains two promoters that are utilized in a tissue-specific
      fashion.

PMID- 8981228
TI  - Expression of IGF-II and H19 mRNA in the neonatal rat during normal maturation
      and after dexamethasone administration.
AB  - In this study, the expression of IGF-II and H19 was examined in the liver,
      skeletal muscle and choroid plexus of the neonatal rat during normal maturation
      and after the administration of dexamethasone. If the two genes share common
      regulatory elements as postulated by an enhancer competition system, their
      patterns of expression should remain similar throughout maturation and after
      treatment with dexamethasone. In the liver, down-regulation of IGF-II and H19
      during maturation and after dexamethasone administration was shown. This is
      consistent with the hypothesis that IGF-II and H19 are regulated by common
      enhancers. In the secretory cells of the choroid plexus, where expression of IGF
      II is known to be biallelic, IGF-II was expressed in both untreated and
      dexamethasone-treated animals, regardless of age, whereas H19 expression was not
      detectable. This is consistent with the postulate that only one gene from each
      allele can be engaged by the enhancers. In skeletal muscle, H19 continues to be
      expressed in the adult after IGF-II is switched off suggesting that IGF-II can
      also be regulated independently of H19.

PMID- 8981227
TI  - Structure of an ovine interferon receptor and its expression in endometrium.
AB  - A sheep type I interferon receptor (oIFNAR1) cDNA was isolated from a lambda-ZAP
      library using a reverse transcription (RT)-PCR product probe generated from
      oestrous endometrial RNA. The oIFNAR1 cDNA was 79, 66 and 95% homologous to
      human, murine and bovine IFNAR1 cDNAs respectively. The encoded receptor was a
      560-amino acid transmembrane protein 80, 66 and 95% similar to human, murine and
      bovine IFNAR1 respectively. Northern blot analysis of endometrial mRNA revealed
      the presence of 6.5, 4.3 and 3.7 kb transcripts. Using semi-quantitative RT-PCR
      the oIFNAR1 mRNA was not found to be down-regulated after 72 h treatment with
      bovine recombinant IFN-alpha I in in vitro experiments with endometrial explants.

PMID- 8981229
TI  - Two variants of the pituitary specific transcription factor Pit-1 in Atlantic
      salmon.
AB  - We have cloned two 1.6 kb cDNAs encoding variants of the POU-type pituitary
      specific transcription factor Pit-1 from Atlantic salmon. Sequence comparison
      with mammalian Pit-1 revealed that the POU domain was highly similar while
      flanking regions were less conserved. The N-terminal region contained three
      insertions relative to mammalian Pit-1, one of these corresponded to the
      insertion found in the alternatively spliced Pit-1a isoform. While two different
      salmon Pit-1 transcripts were expressed, alternative splicing in the 5'-region
      did not appear to contribute to further transcript diversity. Both salmon Pit-1
      cDNAs encoded 39.5 kDa proteins that specifically bind a consensus Pit-1
      recognition sequence in vitro. The salmon Pit-1 proteins also recognized the
      classical octamer motif; however, a point mutation in the POU homeodomain
      abolished this interaction.

PMID- 8981230
TI  - Insulin-like growth factor (IGF)-I A- and B-domain analogues with altered type 1
      IGF and insulin receptor binding specificities.
AB  - Insulin-like growth factor-I (IGF-I) analogues were produced with the aim of
      identifying IGF-I residues that contribute to the specificity of binding to the
      type 1 IGF receptor as opposed to the insulin receptor. Receptor binding
      properties of a series of A- and B-domain analogues were compared using rat L6
      myoblasts, soluble human IGF type 1 receptors and soluble human insulin receptor
      isoforms HIR-A (-Ex11) and HIR-B (+Ex11). IGF-I analogues, [Leu8] IGF-I and
      [Phe59] IGF-I, were shown to exhibit respectively, a 28- and 17-fold decrease in
      affinity for the HIR-A with only a 6- and 5-fold decrease in affinity for the
      human IGF type 1 receptor. In contrast, the analogue [His4] IGF-I was equipotent
      to IGF-I in binding to the soluble type 1 IGF receptor while showing 7-fold and 4
      fold increases in HIR-A and HIR-B binding respectively. Furthermore, [Leu62] IGF
      I was 8-fold less potent than IGF-I in soluble IGF type 1 receptor binding but
      only showed a 2-fold decrease in HIR-A and HIR-B binding. Our study supports the
      conclusion that the co-evolution of the IGF-I and insulin receptor/ligand systems
      has resulted in subtle structural differences in the A- and B-regions of each
      ligand important for defining receptor binding specificity.

PMID- 8981231
TI  - Expression of a prolactin-like factor in preneoplastic and neoplastic mouse
      mammary gland and cells.
AB  - Prolactin is a member of the growth hormone family and is required for the growth
      and terminal differentiation of the mammary gland. Ectopic production of this
      hormone has been reported in several species, including rat, sheep, goat and
      human mammary tissues. In this study, mouse mammary cell lines, xenographs in the
      mammary gland from these cell lines and from hyperplastic alveolar nodules,
      spontaneous tumours, and normal tissues were studied for de novo production of
      this growth factor. Prolactin transcripts were found by reverse transcriptase PCR
      in some neoplastic and preneoplastic tissues and in mouse mammary cell lines,
      NOG8 and CDNR4, but were not detected in the normal mouse mammary gland. Northern
      analysis revealed a 1 kb transcript for both cell lines that co-migrated with the
      prolactin pituitary transcript. Conditioned medium from NOG8 cells was positive
      for prolactin bioactivity by the Nb2 rat lymphoma cell proliferation assay, and
      Western analysis revealed the presence of immunoreactive proteins at M(r) 14,000
      and 60,000. Prolactin-like bioactivity was not detected in conditioned medium
      from CDNR4 cells, but an immunoreactive protein of M(r) 60,000 was detected by
      Western analysis. The mouse mammary cell line, Comma D, was negative for
      prolactin transcripts; however, adenocarcinomas derived from inoculation of Comma
      D cells into the cleared mammary fat pad were positive by reverse transcriptase
      PCR in two of four cases. Hyperplastic outgrowths maintained in the cleared
      mammary fat pad as well as spontaneous tumors were positive for prolactin
      transcripts in one of four cases. These results suggest that prolactin can be
      produced ectopically by the neoplastic mouse mammary gland.

PMID- 8981232
TI  - Mutations of Arg68 of the human chorionic gonadotrophin beta subunit lead to
      reduced secretion.
AB  - The Arg68-Leu69 sequence is invariant in the beta subunits of chorionic
      gonadotrophin and luteinizing hormone from a variety of species. Using site
      directed mutagenesis of the human chorionic gonadotrophin (hCG)-beta cDNA,
      several replacements of Arg68, an Ala replacement of Leu69, and a multiple
      replacement with Ala-Ala-Ala-Ala of the tetrapeptide sequence, Arg68-Leu69-Pro70
      Gly71, were prepared and characterized. The wild-type and mutant cDNAs were
      subcloned into a pRSV expression vector and transiently transfected into CHO
      cells containing a stably integrated gene for bovine a. Concentrations of
      secreted wild-type and mutant hCG-beta subunit and holoprotein were determined
      using radioimmunoassays; potencies, i.e. the ratio of biologic to immunologic
      activity, of several of the mutant heterodimers were measured in vitro via
      gonadotrophin-mediated steroidogenesis in transformed murine Leydig cells (MA
      10). The Leu69-->Ala mutant formed a mutant holoprotein that was essentially
      equipotent with wild-type hormone in the steroidogenesis assay. The Arg68
      replacements with Lys, Ala, and Leu were poorly secreted by the cells, e.g. < 10%
      that of wild-type hCG; however, sufficient quantities of mutant holoproteins
      containing Lys68 and Ala68 were obtained for biological assays, and both
      exhibited greater apparent potencies than wild-type hormone. Likewise, a mutant
      holoprotein containing the Arg68-Leu69-Pro70-Gly71-->Ala-Ala-Ala-Ala multiple
      replacement was apparently more potent than wild-type hormone, but it too was
      secreted at lower levels than wild-type. These results establish that
      replacements of Arg68 in hCG-beta diminish secretion, but the small amount of
      holoprotein that is formed and secreted appears to be of somewhat greater potency
      than wild-type hormone.

PMID- 8981233
TI  - Cellular localization of stem cell factor and c-kit receptor in the mouse nervous
      system.
AB  - We have characterized the cellular localization of stem cell factor (SCF) and c
      kit receptor (c-kitR) in the adult mouse nervous system in situ and in culture by
      using immunocytochemistry. We found that SCF is largely confined to the neuronal
      population in normal brain, whereas c-kitR is expressed by glial cells as well as
      some neurons. We also found that astroglia at an early stage of culture (7 days
      in vitro) are strongly SCF positive and weakly c-kitR positive. Microglia in
      cultures express both SCF and c-kitR, but the immunostaining of SCF is weak and
      diffuse when microglia are cultured in the presence of colony stimulating factor
      1. Northern blot analysis confirmed the expression of mRNAs of c-kit and SCF in
      cultured neurons, astroglia, and microglia. The addition of recombinant SCF to
      astroglia in culture upregulates the expression of mRNAs of nerve growth factor,
      brain derived neurotrophic factor, and ciliary neurotrophic factor. These
      observations suggest that SCF/c-kitR signaling is involved in neuron-neuron as
      well as neuron-glia interactions.

PMID- 8981234
TI  - EGF in combination with depolarization or cAMP produces morphological but not
      physiological differentiation in PC12 cells.
AB  - In response to nerve growth factor (NGF) or basic fibroblast growth factor (bFGF)
      receptor activated Ras/extracellular signal-regulated kinase (ERK) signaling,
      PC12 cells undergo a prototypical neuronal differentiation program, characterized
      by neurite extension and upregulation of voltage-gated ion channels. The
      epidermal growth factor (EGF) receptor also activates Ras/ERK signaling, but
      produces proliferation instead of differentiation. In the presence of
      depolarizing concentrations of KCl, however, EGF elicits neurite outgrowth
      through the synergistic actions of the Ras/ERK and cAMP signaling pathways. To
      assess if EGF and KCl/cAMP elicit the same suite of differentiation events as
      does NGF and bFGF, we used patch clamp recording to determine if EGF in the
      presence of KCl or a cAMP agonist also induced physiological differentiation as
      defined by upregulation of ion channels. Chronic NGF treatment of PC12 cell
      cultures elicited robust morphological differentiation, a threefold increase in
      mean calcium channel current density, and an eightfold increase in mean sodium
      channel current density. Sibling cultures chronically treated with EGF in the
      presence of high KCl or a cAMP agonist also displayed morphological
      differentiation, but had calcium channel current densities which were no larger
      than untreated, undifferentiated cells. Additionally, the increase in mean sodium
      channel current density induced by EGF in the presence of KCl or cAMP was no
      greater than the increase observed with EGF alone. Thus, although EGF in the
      presence of KCl or cAMP is sufficient to induce morphological differentiation as
      defined by neurite outgrowth, synergism of the Ras/ERK and cAMP/PKA signaling
      pathways is not sufficient to promote the fully physiologically differentiated
      PC12 phenotype.

PMID- 8981236
TI  - Grafting of cultured microglial cells into the lesioned spinal cord of adult rats
      enhances neurite outgrowth.
AB  - There is contrasting in vitro and in vivo evidence regarding glial cell
      involvement in central nervous system (CNS) regeneration. This study has
      investigated the histological events that follow implantation of either
      microglia, mixed microglia/astrocytes, or astrocytes into the injured adult rat
      spinal cord. We have conducted an immunohistochemical characterization of the
      cellular profiles within and neuritic extension into various grafts consisting of
      gelfoam (GF) matrices impregnated with cultured microglia and/or astrocytes.
      After 2-5 weeks, prominent neuritic growth was observed into OX-42-immunoreactive
      (IR) microglial implants. These grafts were infiltrated by numerous host cellular
      elements including microvasculature and Schwann cells, and they demonstrated
      conspicuous laminin IR. Often, the patterns for laminin and OX-42 IR in
      microglial grafts were overlapping, suggesting partial expression of laminin on
      transplanted microglial cells. Mixed grafts of microglia and astrocytes
      demonstrated presence of neurites and laminin-IR elements with similar intensity
      as microglial grafts, while astroglial implants showed the least amount of
      neurite ingrowth. Some control implants consisting of cell-free GF showed
      marginal in-growth of neurites in areas of infiltrating OX-42-IR host cells.
      Collectively, our findings support a neurite growth-promoting role of activated
      microglia and suggest that microglia may counteract mechanisms that inhibit CNS
      regeneration. It remains to be determined whether the observed neurite growth
      promoting effects are mediated directly by grafted and/or endogenous microglia,
      or whether this occurs via the recruitment of host Schwann cells.

PMID- 8981235
TI  - Properties of ryanodine receptors in cultured cerebellar granule neurons: effects
      of hexachlorocyclohexane isomers and calcium.
AB  - The binding of [3H]ryanodine was determined in microsomal membrane preparations
      obtained from cultured cerebellar granule cells. A KD of 1 nM and a Bmax of 64
      fmol/mg protein were calculated from saturation experiments. This binding was
      calcium dependent and maximum values were obtained at 100-300 microM Ca+2.
      Caffeine increased [3H]ryanodine binding only at Ca+2 concentrations lower than
      optimum. The binding of [3H]ryanodine was inhibited by ruthenium red, procaine
      and the delta-isomer of hexachlorocyclohexane (delta-HCH). Dantrolene, a
      ryanodine receptor antagonist in skeletal sarcoplasmic reticulum, and the
      pesticide gamma-HCH (lindane) had no effect on [3H]ryanodine binding. The
      obtained binding parameters, the Ca+2 dependence and the effects of the agents
      tested agree with previous reports using brain microsomal membranes, further
      indicating a neuronal localization of [3H]ryanodine binding sites. When the
      interaction between dantrolene and gamma- and delta-HCH was tested, no changes
      were detected on the effects of HCH isomers on [3H]ryanodine binding. Dantrolene,
      which inhibits Ca+2 release from sarcoplasmic reticulum and from unidentified
      internal Ca+2 stores in neurons, also inhibits the intracellular Ca+2
      mobilization induced by gamma-HCH but only marginally that induced by delta-HCH
      in the same preparation of cerebellar granule cells (Rosa et al.; Toxicol Appl
      Pharmacol, in press). Thus, the results obtained in this work verify the presence
      of different intracellular sites of action for the two HCH isomers: the ryanodine
      Ca+2 channel for delta-HCH and an unidentified dantrolene-sensitive Ca+2 channel
      for the gamma-HCH isomer.

PMID- 8981237
TI  - Specific impulse patterns regulate acetylcholinesterase activity in skeletal
      muscles of rats and rabbits.
AB  - In rats, acetylcholinesterase (AChE) activity in the fast muscles is several
      times higher than in the slow soleus muscle. The hypothesis that specific neural
      impulse patterns in fast or slow muscles are responsible for different AChE
      activities was tested by altering the neural activation pattern in the fast
      extensor digitorum longus (EDL) muscle by chronic low-frequency stimulation of
      its nerve. In addition, the soleus muscle was examined after hind limb
      immobilization, which changed its neural activation pattern from tonic to phasic.
      Myosin heavy-chain (MHC) isoforms were analyzed by gel electrophoresis. Activity
      of the molecular forms of AChE was determined by velocity sedimentation. Low
      frequency stimulation of the rat EDL for 35 days shifted the profile of MHC II
      isoforms toward a slower MHCIIa isoform. Activity of the globular G1 and G4
      molecular forms of AChE decreased by a factor of 4 and 10, respectively, and
      became comparable with those in the soleus muscle. After hind limb
      immobilization, the fast MHCIId isoform, which is not normally present, appeared
      in the soleus muscle. Activity of the globular G1 form of AChE increased
      approximately three times and approached the levels in the fast EDL muscle. In
      the rabbit, on the contrary to the rat, activity of the globular forms of AChE in
      a fast muscle increased after low-frequency stimulation. The results demonstrate
      that specific neural activation patterns regulate AChE activity in muscles. Great
      differences, however, exist among different mammalian species in regard to muscle
      AChE regulation.

PMID- 8981239
TI  - Origins of horizontal cell spectral responses in the retina of marine teleosts
      (Centropomus and Mugil sp).
AB  - Intracellular recording and marking of horizontal cells (HCs) were carried out in
      isolated retinas of marine teleosts (Centropomus and Mugil sp.) to identify the
      cellular origins of different spectral types of S-potential. The spectral
      responses recorded under mesopic conditions were classified into four types:
      photopic L, biphasic C(R/G), biphasic C(G/R), and scotopic L(sL). Intracellular
      marking with Lucifer yellow (LY) or Procion yellow (PY) revealed that in the
      Centropomus retina an L-type response was recorded from H1 and H2 cells, C(R/G)
      type from H3 cells, and sL-type from H4 cells. However, in 20% of microelectrode
      penetrations from the photoreceptor surface, the sequential order of response
      appearances was found to be L-, sL-, and C(R/G)-types. In this species, thick
      dendritic processes of H3 and H4 cells are distributed at the same level as the
      cell body. In the Mugil retina, on the other hand, L-type response was recorded
      from H1 cells, C(G/R)-type from H2 cells, C(R/G)-type from H3 cells, and sL-type
      from H4 cells, this sequential arrangement being very regular. In both species,
      the cone-connected H1 cells are small and possess an axon, while the two other
      cone HCs as well as rod-connected H4 cells are axonless. Earlier (Negishi et al.,
      1988) and present findings indicate that there is a wide variety of HC morphology
      and functional organization in the teleost retina.

PMID- 8981238
TI  - Serotonergic function of aging hippocampal CA3 pyramidal neurons:
      electrophysiological assessment following administration of 5,7
      dihydroxytryptamine in the fimbria-fornix and cingulum bundle.
AB  - Serotonergic (5-hydroxytryptamine; 5-HT) neurotransmission has been implicated in
      the regulation of cognitive function and this neurotransmitter system may
      underlie selective neuronal degeneration found in the aging hippocampus. Age
      dependent changes in 5-HT function of hippocampal CA3 subfield pyramidal neurons
      were evaluated in female Fischer 344 rats (2 and 17 months) following denervation
      of the serotonergic afferents to the dorsal hippocampus using the neurotoxin 5,7
      dihydroxytryptamine (5,7-DHT). Vehicle (ascorbic saline) or 5,7-DHT was
      administered bilaterally in the fimbria-fornix/cingulum bundle and dorsal
      pyramidal cell responses to microiontophoretic application of 5-HT, the 5-HT1A
      agonist (+/-)-8-hydroxy-2-(di-N-propylamino) tetralin, the 5-HT1A antagonist WAY
      100,135 and N-methyl-D-aspartate were recorded at 3 weeks post-lesion.
      Independent of changes in sensitivity to the inhibitory effects of 5-HT with
      aging, the time to recovery of cell firing following application of 5-HT was
      significantly increased in the 18 months 5,7-DHT group compared to the 18 month
      Vehicle and 3 month 5,7-DHT groups (3.3- and 2.6-fold, respectively). These
      results demonstrate that serotonergic neurotransmission is altered with aging
      following a selective neurotoxic insult to the hippocampus.

PMID- 8981241
TI  - Detection of delta opioid receptor and N-methyl-D-aspartate receptor-like
      immunoreactivity in retinoic acid-differentiated neuroblastoma x glioma (NG108
      15) cells.
AB  - NG108-15 neuroblastoma cells differentiated with 0.1 M of all-trans retinoic acid
      (RA) were processed for immunohistochemical analysis using polyclonal antisera
      against the delta opioid receptor (DOR) and the N-Methyl-D-Aspartate receptor
      (NMDAR1) to determine the cellular sites for possible functional associations
      between DOR and NMDAR1 receptors. In this study, 6 days of RA treatment resulted
      in prominent morphological differentiation characterized by the appearance of
      numerous axon- and dendrite-like processes and formation of networks between the
      cell clusters. An immunocytochemical approach allowed the demonstration of
      antibody concentration-dependent differences, not evident in ligand binding
      studies, in the distribution of DOR and NMDA receptor protein between cell soma
      and processes. RA-differentiated cultures showed positive DOR-like immunostaining
      (DOR-LI) throughout the cell bodies as well as on the newly acquired processes.
      In contrast, NMDAR1-like immunoreactivity (NMDAR1-LI) in the RA-treated cells was
      detected in the cell soma and processes only with the higher concentration of the
      antiserum. With the lower concentration of the antibody the NMDAR1-LI was not
      detected in the processes and was limited to a punctuate subcellular distribution
      in the soma. The DOR-LI pattern of distribution in NG108-15 cells differentiated
      with RA appeared to be consistent with the DOR-LI detected in the CNS. The NMDAR1
      LI distribution in these cells is similar to brain tissue with respect to its
      presence on the newly acquired processes. However, it differed from brain in that
      a much higher abundance of NMDAR1 receptors was observed in the cell soma. This
      differential distribution of DOR and NMDAR1 receptors in the RA-treated NG108-15
      cells could provide a basis for future studies of drug-induced changes in these
      two receptors.

PMID- 8981240
TI  - Desipramine modulates 3H-ouabain binding in rat hypothalamus.
AB  - We have previously shown that Na+, K(+)-ATPase activity in hypothalamus is
      increased after administration of an acute dose of desipramine, a noradrenaline
      uptake inhibitor (Viola et al., Cell Molec Neurobiol 9:263-271, 1989). In this
      report the same treatment (10 mg per kg) was applied to evaluate 3H-ouabain
      binding in rat brain sections by quantitative autoradiography. Results disclosed
      an increase in the number of ouabain binding sites in hypothalamus but not in
      cerebral cortex. Concomitantly, such acute DMI treatment enhanced K(+)-stimulated
      p-nitrophenylphosphatase activity in hypothalamus membranes whereas it failed to
      modify cerebral cortex membranes. A direct interaction of DMI with the enzyme was
      ruled out since in vitro DMI is known to inhibit the enzyme. It may be speculated
      that DMI indirectly stimulates Na+, K(+)-ATPase through the increase in
      noradrenaline which acts in turn on the external phosphorylated site of the
      enzyme.

PMID- 8981242
TI  - Cytotoxic effects of repin, a principal sesquiterpene lactone of Russian
      knapweed.
AB  - Repin is the principal sesquiterpene lactone isolated from Russian knapweed
      (Centaurea repens), a perennial weed found in many parts of the United States.
      Ingestion of Centaurea repens by horses has been reported to cause a movement
      disorder simulating Parkinson's disease (PD) and nigrostriatal degeneration,
      called equine nigrostriatal encephalomalacia (ENE). To understand the mechanisms
      whereby ingestion of Centaurea repens induces ENE and a PD-like disorder, repin
      cytotoxicity was examined to explore its pathogenetic relationship to ENE and to
      PD. Repin was highly cytotoxic to both PC12 cells and mouse astrocytes in a dose-
      and time-dependent manner. The cytotoxic effects were accompanied by depletion of
      glutathione (GSH), a rise in the level of reactive oxygen species (ROS) and
      damage to cellular membranes. Although repin is a highly reactive electrophile
      that can readily conjugate GSH, GSH depletion may not be the sole mechanism
      underlying repin cytotoxicity as shown by our study using buthionine sulfoximine,
      in which severe GSH depletion did not result in a parallel increase in cell
      death. However, pre-treatment with GSH-glycoside or with lipoic acid provided
      significant protection from repin-induced cell death. These data suggest that
      oxidative stress plays a major role in repin cytotoxicity. Since oxidative stress
      is considered to play a major role in neuronal degeneration accompanied by
      depletion of mitochondrial GSH and an increase in lipid peroxides in the
      substantia nigra of PD, further elucidation of mechanisms of repin neurotoxicity
      may generate clues regarding not only the mechanisms of neuronal degeneration but
      also the possible role of environmental factors in the pathogenesis of PD.

PMID- 8981243
TI  - Bcl-xl-specific antibody labels activated microglia associated with Alzheimer's
      disease and other pathological states.
AB  - This report describes the production of a monoclonal antibody raised against Bcl
      xl, and includes an initial study of bcl-xl expression in neuropathology
      including Alzheimer's disease (AD). Bcl-xl is a potent apoptotic inhibitor and is
      known to be the predominant Bcl-x isoform in brain. To examine the expression of
      bcl-xl in aged brain and neurodegenerative disease, we raised a Bcl-xl-specific
      monoclonal antibody. In aged human brain, the highest bcl-xl expression was
      observed in cerebellum. By immunohistochemistry, significant bcl-xl expression
      was detected in reactive microglia of patients with AD and other neurological
      diseases such as progressive supranuclear palsy. Bcl-xl-positive microglia
      frequently colocalized with beta-amyloid plaques in AD and with activated
      astrocytes in non-AD and AD brains, suggesting a general role for Bcl-xl in
      regions of pathology. High levels of Bcl-xl protein might render microglia more
      resistant to cytotoxic environments such as areas of neurodegeneration and
      astrogliosis.

PMID- 8981244
TI  - Tenascin-C knockout mouse has no detectable tenascin-C protein.
AB  - A recent study by Mitrovic and Schachner (J Neurosci Res 42:710-717, 1995)
      reported the detection of a small amount of truncated tensacin-C (TN-C) in the
      nervous system of the TN-C knockout mice created by Saga et al. (Genes Dev 6:1821
      1831, 1992). The authors suggested that the truncated protein might be
      responsible for the failure to detect any phenotypic abnormalities in the
      knockout mice. We have reexamined the knockout mice in our laboratories by
      Western blot and immunocytochemistry, and have not detected any full-length or
      truncated TN-C protein. In addition, we note that the construction of the
      knockout gene deleted the signal sequence, so if any residual truncated protein
      were produced it would be trapped in the cytoplasm, and therefore inaccessible to
      extracellular ligands or receptors. We therefore conclude that the TN-C knockout
      created by Saga et al. is a valid TN-C null.

PMID- 8981245
TI  - Comparative study of pyridoxine-alpha, beta-glucosides, and phosphopyridoxyl
      lysine as a vitamin B6 nutrient.
AB  - The nutritional effects of pyridoxine-alpha-glucoside (PN-alpha-Glc), pyridoxine
      5' beta-glucoside (PN-5' beta-Glc) and epsilon-N-(phosphopyridoxyl)-lysine (PNP
      Lys) were examined by means of: 1) transport across the intestinal wall using
      everted rat intestine, 2) metabolic conversion by liver or kidney homogenate, and
      3) oral administration of the compound to B6-deficient rats and the subsequent
      analysis of B6 derivatives found in plasma. Using everted sacs prepared from rat
      small intestine, PN-alpha-Glc was transported into the serosal side in its intact
      form. On the other hand, a part of PN-5' beta-Glc was found as PN on the serosal
      side (PN-5' beta-Glc: PN = 2:1). When PN-alpha-Glc, PN-5' beta-Glc or PNP-Lys was
      incubated with liver or kidney homogenate for 3 h at pH 6.0, PN-alpha-Glc was
      hydrolyzed to PN (6%), while there was no hydrolysis of PN-5' beta-Glc. After 30
      min of administration of each B6 derivative to B6-deficient rats, blood was
      collected from the heart, and the B6-derivatives found in plasma were analyzed.
      It was ascertained that PN-alpha-Glc served as well as PN as a B6 nutrient, while
      PN-5' beta-Glc and PNP-Lys were not easily metabolized to the coenzyme form,
      pyridoxal 5'-phosphate.

PMID- 8981246
TI  - A positive correlation between catalase activity and ascorbate uptake in the
      tissues of guinea pigs and cultured cells of mammals.
AB  - We recently reported that the concentration of supplemental ascorbate which
      inhibits cell growth is positively related to intracellular catalase activity. It
      is assumed that the cells with high catalase activity are resistant to high
      concentrations of ascorbate since catalase can decompose hydrogen peroxide (H2O2)
      induced by the auto-oxidation of ascorbate in cultured medium. In this study, we
      investigated whether intracellular catalase activity affects the uptake of
      ascorbate into animal tissue and cultured cells. Ascorbate concentrations in the
      tissues of guinea pigs and various cultured cells, with and without
      supplementation of ascorbate, were determined to evaluate the efficiency of
      ascorbate uptake. We found a positive correlation between the efficiency of
      ascorbate uptake and catalase activity in various tissues of guinea pigs (r =
      0.767, p < 0.05). Furthermore, a positive correlation between the two was also
      found in various species of cultured cells. This study indicates that tissues and
      cells with higher efficiency of ascorbate uptake are required for higher catalase
      activity, presumably for the decomposition of H2O2 from ascorbate.

PMID- 8981247
TI  - Nutritional status of vitamin A and E in institutionalized elderly people in
      Granada (Spain).
AB  - A study has been carried out on the nutritional status of vitamin A and E in 93
      institutionalized elderly people in Granada (Spain) by studying their vitamin
      intake and the serum values of retinol and alpha-tocopherol. The influence of
      lipid intake and lipids in plasma has been also discussed. The vitamin A intake
      is higher than the recommended amount and represent 209% DR in men and 217% DR in
      women. The vitamin E intake is deficient in 33% of the men and 27% of the women.
      The serum values of retinol indicate that 11% of the women have a deficiency (<
      0.7 microM), and that 39% of the men and 32% of the women have low values (0.7
      1.22 microM). As for the serum values of alpha-tocopherol, 6% of the women have
      deficient values, and 82% of the men and 37% of the women have low values (11.6
      23.2 microM).

PMID- 8981248
TI  - Change in glucose homeostasis in rats by long-term magnesium-deficient diet.
AB  - It is widely known that hypomagnesemia is one of the symptoms observed in
      diabetic patients. This study was performed to assess the effect of chronic
      magnesium (Mg) deficiency on glucose metabolism in rats. Male Sprague-Dawley rats
      (at the age of four weeks) were given a Mg-deficient diet or a control diet for
      two to eight weeks. The rats were orally administered sucrose solution (2 g/kg
      BW) every two weeks, and blood was drawn from a tail vein before and 15 min after
      sucrose loading to determine the concentrations of blood glucose and plasma
      insulin. At the same time, other rats in a non-fasted condition were sacrificed
      by decapitation (rats sacrificed at eight weeks were rats used for sucrose
      loading). The epididymal fat pads were immediately removed and adipocytes were
      isolated. The amount of glucose transporter 4 (GLUT4) in the plasma membranes and
      low-density microsomal membranes prepared from the adipocytes was measured by
      immunoblotting to estimate the influence of chronic Mg deficiency on glucose
      metabolism at the cellular level. In addition, plasma biochemical parameters and
      muscle mineral contents were also evaluated. The glucose concentration in fasted
      blood was significantly lower in Mg-deficient rats than in control rats
      throughout the experiment period. The feeding of a Mg-deficient diet also
      attenuated the response of blood glucose and plasma insulin: the glucose level in
      blood tended to be lower in Mg-deficient rats at 15 min after oral sucrose
      administration, and the difference was significant at two and eight weeks. The
      plasma insulin level in Mg-deficient rats was also lower, reaching a significant
      difference at two weeks. When animals were sacrificed in a non-fasted condition
      at 2-week intervals, the plasma glucose level was also significantly decreased in
      Mg-deficient rats as compared to control rats throughout the experiment period.
      The plasma insulin level in non-fasted Mg-deficient rats was also significantly
      decreased at two and six weeks. The Mg-deficient diet increased plasma
      triglyceride, but the difference was significant only at four weeks, and plasma
      cholesterol remained unchanged. The plasma Mg level was markedly lower in Mg
      deficient rats throughout the experiment period. In Mg-deficient rats, the Mg
      content in muscle was significantly reduced at two and eight weeks, whereas the
      calcium and sodium contents were significantly increased throughout the
      experiment period. In Mg-deficient rats, the degree of translocation of GLUT4 to
      plasma membranes in the adipocytes stimulated by insulin was reduced only at
      eight weeks. In conclusion, since fasted and non-fasted blood glucose levels and
      the response of blood glucose to sucrose loading were decreased in Mg-deficient
      rats, it is suggested that Mg deficiency induces changes in the glucose
      metabolism via impaired glucose absorption in the intestine or an altered glucose
      uptake in the liver and/or peripheral tissues.

PMID- 8981249
TI  - Effects of dietary n-3/n-6 and polyunsaturated fatty acid/saturated fatty acid
      ratios on platelet aggregation and lipid metabolism in rats.
AB  - We studied the effects of dietary lipids on platelet aggregation and lipid
      metabolism in rats by varying the n-3/n-6 ration while maintaining the
      polyunsaturated fatty acid/saturated fatty acid (P/S) ratio fixed, and vice
      versa. After two weeks, the platelet counts decreased as the dietary n-3/n-6
      ratio rose, and platelet aggregation was sufficiently suppressed at the ratio of
      0.2. Differences in the dietary P/S ratio, however, did not affect either the
      platelet counts nor platelet aggregation. As the dietary n-3/n-6 ratio rose, the
      proportion of arachidonic acid (AA) in the plasma and the phospholipids (PL) of
      the platelets and aorta decreased gradually, whereas the proportion of
      eicosapentaenoic acid (EPA) in each tissue increased gradually. The proportion of
      EPA was higher in the platelets than in the aorta, while that of docosahexaenoic
      acid (DHA) was higher in the latter. The production of platelet thromboxane A2
      (TXA2) and aortic prostacyclin (PGI2) showed sharp declines, from the values for
      the n-3/n-6 ratio of 0.02 (control) to those for 0.5. These results suggest that
      the n-3/n-6 ratio of dietary fats necessary to ensure the suppression of platelet
      aggregation in normal rats would be at least 0.2 and no more than 0.5.

PMID- 8981250
TI  - Changes of serum alkaline phosphatase isoenzymes in fasted rats.
AB  - Changes of serum alkaline phosphatase (sALP) isoenzymes under fasting conditions
      were examined using polyacrylamide gel electrophoresis (PAGE), amino-acids (L
      phenylalanine (L-Phe), L-homoarginine (L-HArg)) inhibition and wheat germ
      agglutinin (WGA) treatment. The sALP of non-fasted rats was separated into three
      bands (S1, S2, S3) by PAGE. The molecular weight (M.W.) of S1 corresponded to
      that of an isoenzyme found in the ileum. By the addition of L-Phe, the staining
      intensity of S1 was weakened, S2 and S3 remained unchanged and the total activity
      of the isoenzymes extracted from intestine decreased. On the other hand, the
      activity of isoenzymes extracted from kidney and bone decreased by the addition
      of L-HArg. Therefore, S1 was judged to be derived from intestine. The activities
      of total sALP and S1 decreased from 16 h of fasting. Total sALP activity and sALP
      activity of the supernatant prepared by WGA treatment decreased, whereas the ALP
      activity of the precipitate (difference between total sALP activity and
      supernatant sALP activity) did not change. The activity band of the precipitate
      corresponded to that of S3 by PAGE. Therefore, S3 was judged to be derived from
      bone. In conclusion, under fasting conditions, the activity of S1 decreased while
      the activities of S2 and S3 remained unchanged.

PMID- 8981251
TI  - Effects of intermittent food restriction and refeeding on energy efficiency and
      body fat deposition in sedentary and exercised rats.
AB  - The effects of body weight cycling on energy metabolism and body fat accumulation
      were examined in sedentary and exercised rats. Ten rats were sacrificed before
      the experiment to obtain basal data, and then 90 rats were divided into three
      groups; control (CN), food restricted (FR) and weight cycling (WC). Food intake
      in rats of the FR group was restricted constantly to 70% of the intake of the CN
      group. The rats of WC group were subjected to four bouts of weight cycling
      consisting of 7-days food restriction followed by 7-days refeeding, but were fed
      the same total amount of dietary energy as that of the FR group throughout the
      experimental period. The rats of all groups were meal-fed twice a day. Half of
      the rats in each group were exercised by running on a treadmill (30 min/day)
      throughout the experimental period. The body weight, abdominal adipose tissue
      weight, body fat, body protein and energy restoration for the study in both
      sedentary and exercised groups were greater in the WC group than in the FR group.
      The resting metabolic rate of the WC group after four bouts of weight cycling was
      lower than that of the FR group in the sedentary rats, but this difference was
      not observed in the exercised rats. Also, the thermic effect of food (TEF) in the
      sedentary rats for 6 h after a meal was significantly less in the WC group as
      compared to that of the FR group. However, the TEF for the exercised rats was not
      different between the two groups. The serum insulin level, activities of
      lipogenic enzymes and lipoprotein lipase in adipose tissue for the sedentary rats
      of the WC group were higher than those of the FR group, but did not differ in the
      exercised rats. These results suggest that weight cycling increases body fat
      deposition and energy efficiency by decreasing energy expenditure, particularly
      the TEF, and that exercise training can alleviate the effects of weight cycling
      on the energy metabolism.

PMID- 8981252
TI  - Effects of refeeding diets on emeriamine-induced fatty liver in fasting rats.
AB  - We recently reported that fatty liver and hypertriglyceridemia are easily induced
      by the administration of an inhibitor of fatty acid oxidation (emeriamine; (R)-3
      amino-4-trimethylaminobutyric acid) to fasting rats, and that these conditions
      are not accompanied by the increased de novo synthesis of fatty acid [J. Nutr.
      Sci. Vitaminol., 42, 111-120, (1996)]. To study whether emeriamine-induced fatty
      liver is affected by nutrients during recovery from fatty acid oxidation
      inhibition, we fed rats with either a high-carbohydrate (HCHO) diet or a high-fat
      (HFAT) diet. Rats fed an HCHO diet following the administration of emeriamine
      showed a marked decrease in serum and hepatic triglycerides, and a marked
      increase in hepatic glycogen. The lower levels of serum and hepatic triglycerides
      were accompanied by decreased activities of the NADPH-generating enzymes such as
      malic enzyme and glucose-6-phosphate dehydrogenase. By contrast, rats fed an HFAT
      diet showed less significant changes in hepatic triglyceride and glycogen levels.
      These results suggest a reciprocal relationship between the triglyceride level
      and glycogen accumulation caused by HCHO diet during recovery from emeriamine.

PMID- 8981253
TI  - Differences in the influence of AIN-purified and non-purified diets on the
      development of hypertension in SHR and DOCA-salt hypertensive rats.
AB  - The influence of non-purified and AIN purified diets on the development of
      hypertension was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive
      rats and SHRs. For DOCA-salt hypertensive rats, the development of hypertension
      was slower in rats fed the AIN 76-purified diet than in those fed the non
      purified diet throughout the experimental period of about five weeks. In an
      experiment using spontaneously hypertensive rats (SHRs), 4-week-old rats were fed
      either a non-purified diet, a AIN76-purified diet or a AIN93G-purified diet for
      about nine weeks. In the first 1-2 weeks, the blood pressure was lower in the
      SHRs fed the AIN93G-purified diet than in those fed the non-purified diet.
      However, no significant difference in blood pressure was observed within the SHR
      group thereafter.

PMID- 8981254
TI  - Evaluation of urinary pyridinoline in healthy adults and patients with rheumatoid
      arthritis by an improved high-performance liquid chromatographic assay.
AB  - A modified method for the determination of pyridinoline using high-performance
      liquid chromatography (HPLC) has been applied to analyze the urine of healthy
      adults and patients with rheumatoid arthritis. The concentrations of pyridinoline
      in the urine of healthy Japanese men and women (average age: 50.6 and 51.8 yr,
      respectively) during morning fasting were 28.8 +/- 2.8 (SEM) and 34.8 +/- 3.5
      nmol/mmol creatinine, respectively. In the case of patients with rheumatoid
      arthritis, the urinary concentration of pyridinoline was 49.1 +/- 8.3 nmol/mmol
      creatinine (women, average age, 61.1 yr), which was significantly higher than
      that of healthy women of the same age (p < 0.05). This study supports the
      application of HPLC for urinary pyridinoline analysis and as a screening test for
      patients with bone disease.

PMID- 8981255
TI  - Calcitonin decreases corticosterone-induced skeletal muscle calpain activity.
AB  - The effects of calcitonin (CT) administration on calcium (Ca) concentrations in
      plasma and skeletal muscle as well as the calpain activity of skeletal muscle
      were examined in young growing male rats treated with corticosterone (CTC). The
      rats received subcutaneous injections of CTC (5 mg/100 g body weight/day), or
      both CTC and CT (100 m unit/100 g body weight/day) for four days. Control rats
      received placebos. The rats were sacrificed 24 h after the final injections, and
      blood was taken followed by dissections to remove gastrocnemius and extensor
      digitorum longus muscles. Plasma Ca concentration was increased and muscle Ca
      concentration and its calpain activity tended to be increased by CTC. The CTC
      induced increases in muscle Ca concentration and its calpain activity were
      significantly minimized by the simultaneous injection of CT. However, CTC-induced
      hypercalcemia was not minimized by CT. The present observations indicate that CT
      decreases Ca concentration in skeletal muscle cell and its calpain activity,
      followed by a suppression of muscle proteolysis in rats treated with CTC.

PMID- 8981256
TI  - Calretinin immunoreactivity in pineal gland of different mammals including man.
AB  - Calretinin (CR) is a calcium-binding protein, found in a variety of organs and
      systems such as the central nervous system and the pineal gland. It was first
      thought to be a specific neuronal marker but this selectivity is now in question
      since CR has been demonstrated in avian thymus, rat ovary, rat and guinea pig
      inner ear, rat testis, and chicken and rat pineal gland. To contribute to the
      knowledge of the presence of CR-positive cells in the pineal parenchyma of rat
      and other mammalian including man, we performed immunocytochemistry on pineal
      glands of gerbils, rats, goats, cows, and humans, using a CR anti-serum. To
      confirm it was actually CR that was demonstrated, we performed Western Blot
      analyses. Finally, to precisely identify the nature of CR-positive cells we
      accomplished double-labelling immunofluorescence, using antisera against some
      nerve cell specific cytosquelettal proteins such as MAP-5, MAP-2, NF-L, NF-M, and
      NF-H. CR-positive cells were found in all pineal glands studied. These cells all
      possess a round, oval, or polygonal-shaped perikaryon sending one or more
      processes of different lengths into the glandular parenchyma. There is a lack of
      CR immunoreactivity in the nucleus and cell organelles while the cytosol contains
      a high concentration of this protein. Nevertheless, there are some slight
      differences between species, especially concerning the number of reactive cells
      and their relationships with different parenchymal structures such as blood
      vessels or acervuli. Among the CR-positive cells, only a few were actually nerve
      cells, contributing probably to an intrinsic innervation of the gland. The
      remaining CR-reactive cells seem to correspond mostly to pinealocytes in a
      specific histophysiological state and possibly to neuron-like cells. The
      significance of the CR-positive cells in the pineal glands remains to be
      elucidated.

PMID- 8981257
TI  - Melatonin-induced T-helper cell hematopoietic cytokines resembling both
      interleukin-4 and dynorphin.
AB  - We have reported that melatonin exerts colony stimulating activity and rescues
      bone marrow cells from apoptosis induced either in vivo or in vitro by cancer
      chemotherapy compounds. We proposed that melatonin regulates interleukin-4 (IL-4)
      production in bone marrow T-helper cells and that IL-4 stimulates adherent
      stromal cells to produce colony stimulating factors (CSF). However, in further
      investigations we did not find any direct evidence of the ability of melatonin to
      stimulate IL4. We found that besides anti-IL4 monoclonal antibody (mAb), the
      opioid antagonist naltrexone also neutralized the colony stimulating activity and
      part of the hematopoietic protection exerted by melatonin. SDS-PAGE and
      immunoblotting analysis of supernatants of bone marrow T-helper cells incubated
      overnight with melatonin revealed the presence of two proteins with an apparent
      molecular weight of 15 and 67 kDa, which were recognized by both anti-common
      opioid sequence (Tyr-Gly-Gly-Phe) and anti-IL4 mAbs. When Abs against known
      opioid peptides were tested, only anti-dynorphin B Ab labeled the 67 kDa but not
      the 15 kDa protein. These melatonin-induced-opioids (MIO) were separated by gel
      filtration. The lower molecular weight MIO (MIO15) seems to mediate the
      naltrexone-sensitive hematopoietic effects of melatonin. Consistently, we found
      the presence of opioid receptors in adherent bone marrow cells. Apparently, the
      higher molecular weight protein, MIO67, was responsible for the naltrexone
      insensitive part of the melatonin-induced hematopoietic rescue. These melatonin
      induced T-helper cell products which resemble both IL-4 and dynorphin B might
      represent a new family of opioid peptides with hematopoietic and immune
      functions.

PMID- 8981258
TI  - Prenatal development of the sheep pineal gland: an ultrastructural study.
AB  - The ultrastructure of the pineal gland of 32 sheep embryos was studied from day
      54 of development through birth. Embryos were arranged in four age-groups,
      defined in terms of the most relevant histological features: group 1 (54 to 67
      days of prenatal development), group 2 (71 to 92 days), group 3 (98 to 113 days),
      and group 4 (118 to 150 days). A primary cell type, designated the pinealoblast,
      was observed from 54 days until birth; ultrastructurally, this cell was found to
      contain all the organelles required for hormone synthesis. A second cell
      population, classified as interstitial cells by virtue of their location among
      pinealoblasts, appeared at 78 days gestation and persisted until birth.
      Interstitial cells were scarce and exhibited tropism for the perivascular space.
      From 118 days gestation until birth, a third cell type, termed the pigmented
      cell, was visible. Pigmented cells, whose ultrastructural characteristics
      differed from those of pinealoblasts, contained a large number of pigment
      granules of varying size and shape. The pineal gland of developing sheep embryos
      showed considerable innervation and abundant vascularization; this, together with
      certain ultrastructural characteristics, suggests that the gland has a secretory
      function in uterine life.

PMID- 8981259
TI  - Retinal melatonin is not involved in corneal mitotic rhythms in the Japanese
      quail: effects of formoguanamine hydrochloride and eye-lid suture.
AB  - Relation between retinal melatonin and corneal mitotic rhythms in the Japanese
      quail was investigated in experiments manipulating the ocular physiology by
      treatments with formoguanamine hydrochloride (FG) and eye-lid suture. In
      experiment 1, we investigated the effects of FG, which is known to induce
      photoreceptor degeneration, on retinal melatonin and corneal mitotic rhythms. FG
      treatment completely abolished the retinal melatonin rhythms in both LD 12:12 and
      constant darkness (DD), but the corneal mitotic rhythm was maintained with high
      mitotic rate in darkness under a LD cycle and subjective night under DD. The
      result suggests that 1) the photoreceptor cells in the retina are the site for
      melatonin production and/or for the oscillator which drives the circadian rhythm
      in retinal melatonin, and 2) melatonin is not involved in generation of the
      corneal mitotic rhythm. In experiment 2, we investigated the effects of eye-lid
      suture, which is known to induce eye enlargement and bulgy cornea, on the retinal
      melatonin and corneal mitotic rhythms. Eye-lid suture abolished the corneal
      mitotic rhythm in both LD and DD, with a high mitotic rate being maintained
      throughout 24 hr. But retinal melatonin maintained its rhythm with high levels in
      darkness under a LD cycle and in subjective night under DD. The result suggests
      that 1) bulgy cornea in the sutured eye was induced by the increase in mitotic
      rate in the light period, and 2) disappearance of the corneal mitotic rhythm does
      not have a relation to retinal melatonin. These results suggest that retinal
      melatonin is not involved in generation of the corneal mitotic rhythm and that
      there are two circadian clock systems in the eye.

PMID- 8981260
TI  - Ontogeny of pineal melatonin rhythm in rats under 12:12-hr and 14:14-hr
      light:dark conditions.
AB  - The aim of the study was to determine whether a discrepancy between the
      genetically determined endogenous circadian period and an abnormally long
      Zeitgeber period disturbs the development of melatonin synthesis. Breeding pairs
      of rats were kept under 12:12- or 14:14-hr light:dark (LD) conditions. Pineal
      melatonin contents in the offspring were measured by radioimmunoassay. At 2 weeks
      of age high melatonin contents were found from lights-off to lights-on in both
      conditions suggesting dominance of the photic regulation. At 3 weeks of age the
      signs of the circadian regulation in the melatonin profiles were evident: a lag
      period after the light offset in control conditions and a significant decline
      before the light onset in both conditions. However, in 14:14-hr LD conditions the
      melatonin content did not decrease to daytime levels until the lights were on.
      This could suggest incomplete maturation of the circadian system. The phase
      relationships between the melatonin peak and LD cycle were different in the two
      conditions. A statistically significant LD difference was first found at the age
      of 8-10 days in male pups and at 14 days in female pups under both lighting. The
      results suggest that the abnormally long LD cycle did not cause any major
      disorders in the development of photic or circadian regulation of the melatonin
      synthesis.

PMID- 8981261
TI  - The L-type Ca2+ channel is involved in microvesicle-mediated glutamate exocytosis
      from rat pinealocytes.
AB  - Pinealocytes, parenchymal cells of the pineal gland, secrete glutamate through
      microvesicle-mediated exocytosis upon depolarization by KCl in the presence of
      Ca2+, which is involved in a novel paracrine-like intercellular signal
      transduction mechanism in neuroendocrine organs. In the present study, we
      investigated whether or not the L-type Ca2+ channel is involved in the
      microvesicle-mediated glutamate secretion from cultured rat pinealocytes.
      Nifedipine, a specific antagonist of the L-type Ca2+ channel, inhibited the
      Ca(2+)-dependent glutamate exocytosis by 48% at 20 microM. Other L-type Ca2+
      channel antagonists, such as nitrendipine, showed similar effects. 1,4-Dihydro
      2,6-dimethyl-5-nitro-4 [2-(trifluoromethyl)-phenyl]-3-pyridinecarboxylic acid
      methyl ester (BAY K8644), an agonist of the L-type Ca2+ channel, at 1 microM, on
      the other hand, stimulated the glutamate exocytosis about 1.6-fold. Consistently,
      these Ca2+ channel antagonists inhibited about 50% of the Ca2+ uptake, whereas
      BAY K8644 increased the uptake 5.3-fold. An antibody against the carboxyl
      terminal region of the rabbit L-type Ca2+ channel recognized polypeptides of
      pinealocytes with apparent molecular masses of 250 and 270 kDa, respectively, and
      immunostained the plasma membrane region of the pinealocytes. These results
      strongly suggested that the entry of Ca2+ through L-type Ca2+ channel(s), at
      least in part, triggers microvesicle-mediated glutamate exocytosis in
      pinealocytes.

PMID- 8981262
TI  - Microvesicle-mediated exocytosis of glutamate is a novel paracrine-like chemical
      transduction mechanism and inhibits melatonin secretion in rat pinealocytes.
AB  - Mammalian pinealocytes are neuroendocrine cells that synthesize and secrete
      melatonin, these processes being positively controlled by norepinephrine derived
      from innervating sympathetic neurons. Previously, we showed that pinealocytes
      contain a large number of microvesicles (MVs) that specifically accumulate L
      glutamate through a vesicular glutamate transporter and contain proteins for
      exocytosis such as synaptobrevin 2 (VAMP2). These findings suggested that the MVs
      are counterparts of synaptic vesicles and are involved in paracrine-like chemical
      transduction in the pineal gland. Here, we show that pinealocytes actually
      secrete glutamate upon stimulation by KCl in the presence of Ca2+ at 37 degrees
      C. The ability of glutamate secretion disappeared when the cells were incubated
      at below 20 degrees C. Loss of the activity was also observed on successive
      stimulation, but it was recovered after 12 hr incubation. A low concentration of
      cadmium chloride or omega-conotoxin GVIA inhibited the secretion. Botulinum
      neurotoxin E cleaved synaptic vesicle-associated protein 25 (SNAP-25) and thus
      inhibited the secretion. The released L-glutamate stimulated pinealocytes
      themselves via glutamate receptor(s) and inhibited norepinephrine-stimulated
      melatonin secretion. These results strongly suggest that pinealocytes are
      glutaminergic paraneurons, and that the glutaminergic system regulates negatively
      the synthesis and secretion of melatonin. The MV-mediated paracrine-like chemical
      transduction seems to be a novel mechanism that regulates hormonal secretion by
      neuroendocrine cells.

PMID- 8981264
TI  - Preventing non-family child abductions: are children aware they are being
      followed?
AB  - Australia, the United States, and other developed countries, offer elementary
      school programs that heighten childrens' awareness about the possibility of
      abduction. To examine the effectiveness of such programs, an investigation was
      conducted of the proportion of elementary school children previously taught about
      "stranger" abduction and who detected they were being followed. Fifteen children
      were observed on four separate occasions during a seven-month period. Only 3% of
      the observations were detected by children. Several reasons are proposed for the
      poor detection rate, and recommendations for elementary school programs are made.

PMID- 8981263
TI  - Who dispenses pharmaceuticals to children at school?
AB  - Use of both prescription and non-prescription pharmaceuticals has increased among
      children. Many of these drugs are taken during school hours and dispensed by
      school personnel who are not health professionals. They know little or nothing
      about the drugs themselves or the medical conditions requiring their use. This
      survey examined the extent to which pharmaceuticals are dispensed in schools in
      one Florida county. Public elementary, middle, and high schools and six private
      schools were surveyed for one week. All medications dispensed by school personnel
      during that time were recorded. Of 28,134 children surveyed, 1,016 children
      received 5,411 doses of medication. Thirty-one categories of drugs were dispensed
      including controlled substances. Methylphenidate was the most widely dispensed
      drug, comprising about half of all the medications given in school. Medication
      use was evaluated in terms of gender, race, and socioeconomic status of the
      children.

PMID- 8981265
TI  - Gender representation in illustrations, text, and topic areas in sexuality
      education curricula.
AB  - A content analysis instrument was developed to examine differences in gender
      representation in sexuality education curricula. Fourteen middle school and high
      school curricula, published between 1985 and 1995, were examined. Variables
      included illustrations, noun/pronoun usage, and specific topics within the two
      categories of biological function and mutual interest. The study examined
      differences in gender representation in illustrations, photographs, cartoons,
      drawings, and text. Omission of sexuality topics related to gender also was
      examined. Little difference occurred within the text of the curricula in noun and
      pronoun usage. Illustrations were few in number, but showed greater female
      representation. Greater male representation occurred in topics related to drug
      use, sexual exploitation, sexual desire, and homosexuality. Topics with greater
      female representation included body image, diseases of the reproductive organs,
      and hygiene.

PMID- 8981266
TI  - Youth risk behavior surveillance--United States, 1995.
AB  - Priority health-risk behaviors that contribute to the leading causes of
      mortality, morbidity, and social problems among youth and adults often are
      established during youth, extend into adulthood, and are interrelated. The Youth
      Risk Behavior Surveillance System (YRBSS) monitors six categories of priority
      health-risk behaviors among youth and young adults: behaviors that contribute to
      unintentional and intentional injuries, tobacco use, alcohol and other drug use,
      sexual behaviors, unhealthy dietary behaviors, and physical inactivity. The YRBSS
      includes both a national school-based survey conducted by CDC and state and local
      school-based surveys conducted by state and local education agencies. This report
      summarizes results from the national survey, 35 state surveys, and 16 local
      surveys conducted among high school students from February through May 1995. In
      the United States, 72% of all deaths among school-age youth and young adults
      result from four causes: motor vehicle crashes, other unintentional injuries,
      homicide, and suicide. Results from the 1995 YRBSS suggest that many high school
      students practice behaviors that may increase their likelihood of death from
      these four causes: 21.7% had rarely or never used a safety belt, 38.8% had ridden
      with a driver who had been drinking alcohol during the 30 days preceding the
      survey, 20.0% had carried a weapon during the 30 days preceding the survey, 51.6%
      had drunk alcohol during the 30 days preceding the survey, 25.3% had used
      marijuana during the 30 days preceding the survey, and 8.7% had attempted suicide
      during the 12 months preceding the survey. Substantial morbidity and social
      problems among school-age youth and young adults also result from unintended
      pregnancies and sexually transmitted diseases, including HIV infection. YRBSS
      results indicate that in 1995, 53.1% of high school students had experienced
      sexual intercourse, 45.6% of sexually active students had not used a condom at
      last sexual intercourse, and 2.0% had ever injected an illegal drug. Among
      adults, 65% of all deaths result from three causes: heart disease, cancer, and
      stroke. Most of the risk behaviors associated with these causes of death are
      initiated during adolescence. In 1995, 34.8% of high school students had smoked
      cigarettes during the 30 days preceding the survey, 39.5% had eaten more than two
      servings of foods typically high in fat content during the day preceding the
      survey, and only 25.4% had attended physical education class daily. YRBSS data
      are being used nationwide by health and education officials to improve national,
      state, and local policies and programs designed to reduce risks associated with
      the leading causes of mortality and morbidity. YRBSS data also are being used to
      measure progress toward achieving 21 national health objectives and one of eight
      National Education Goals.

PMID- 8981267
TI  - Advancement of the insertion of the biceps brachii muscle: a technique for
      increasing elbow flexion force.
AB  - A new technique for increasing weak flexion force of the elbow in patients with
      brachial plexus injuries is reported. The concept of this procedure is to
      increase the moment arm of the biceps brachii muscle by moving the point of
      action distally. Advancement of the insertion of the biceps brachii muscle was
      performed with an anterior approach to the radius. The biceps tendon was stripped
      off the radius at its insertion. A hole was dug into the radius 2 cm distal to
      the original insertion. The biceps tendon was then reattached to the drill holes
      made in the distal edge of the initial hole with the elbow in 30 degrees of
      flexion. After immobilization in 70 degrees of flexion for 5 weeks, range-of
      motion exercises were initiated. This procedure was applied in six cases of
      brachial plexus injury. Flexion force at the elbow was increased, and the initial
      motion of elbow flexion has become very smooth in all patients. Consequently the
      activities of daily living are easier to perform. This procedure is simple and
      involves no functional or tissue sacrifice.

PMID- 8981268
TI  - Plate fixation of comminuted olecranon fractures: an in vitro biomechanical
      study.
AB  - The stiffness, cyclic stability, and failure strength of posterior and lateral
      plating were compared in an in vitro model of a comminuted olecranon fracture.
      Loading was applied to the brachialis and triceps while displacements of the
      olecranon were measured with an electromagnetic tracking device in six degrees of
      freedom. No statistical difference was seen in the cyclic or static stability of
      either plating method. The triceps tendon suture attachment failed during
      destructive testing in each case between 300 and 500 N of applied loading. No
      gross failure of the bony fixation of the implant occurred before suture failure.
      These results suggest that both plating methods are likely to afford adequate
      stability to permit early protected postoperative range of motion.

PMID- 8981269
TI  - Biomechanical analysis of tension band fixation for olecranon fracture treatment.
AB  - This study assessed the strength of various tension band fixation methods with
      wire and cable applied to simulated olecranon fractures to compare stability and
      potential failure or complications between the two. Transverse olecranon
      fractures were simulated by osteotomy. The fracture was anatomically reduced, and
      various tension band fixation techniques were applied with monofilament wire or
      multifilament cable. With a material testing machine load displacement curves
      were obtained and statistical relevance determined by analysis of variance. Two
      loading modes were tested: loading on the posterior surface of olecranon to
      simulate triceps pull and loading on the anterior olecranon tip to recreate a
      potential compressive loading on the fragment during the resistive flexion. All
      fixation methods were more resistant to posterior loading than to an anterior
      load. Individual comparative analysis for various loading conditions concluded
      that tension band fixation is more resilient to tensile forces exerted by the
      triceps than compressive forces on the anterior olecranon tip. Neither wire
      passage anterior to the K-wires nor the multifilament cable provided
      statistically significant increased stability.

PMID- 8981272
TI  - Practical guidelines to safe surgery about the subscapularis.
AB  - Surgical mobilization of an adherent or retracted subscapularis tendon is often
      necessary whenever an attempt is made to restore function to the glenohumeral
      joint subsequent to failed anterior reconstructive surgery. Surgical guidelines
      drawn from this study emphasize how a surgeon might accomplish this task
      effectively and avoid denervating the subscapularis, a muscle that is essential
      to anterior glenohumeral stability and strength. In this study we examined
      subscapularis innervation in 11 fresh-frozen cadaveric shoulders. The position of
      the subscapular nerve insertion points were recorded relative to easily
      identified surgical landmarks such as the axillary nerve, the conjoined tendon,
      and the anterior glenoid rim. The palpable anterior border of the glenoid rim
      deep to the subscapularis along with the medical border of the conjoined tendon
      can serve as guides to the subscapularis nerve insertion points, because all the
      nerves are no closer than 1.5 cm medial to these landmarks for all positions of
      humeral rotation in the unelevated arm. The lower subscapular nerve was found
      immediately posterior or just lateral to the axillary nerve. During a standard
      deltopectoral approach potential injury to the subscapularis innervation can be
      minimized by locating and protecting the axillary nerve, because it serves as a
      guide to the insertion point of the lower subscapularis nerve, the nerve closet
      to the surgical field.

PMID- 8981271
TI  - Management of partial-thickness rotator cuff tears.
AB  - Partial-thickness tearing of the rotator cuff is common; however, relatively
      little is written on the subject. We reviewed 39 patients with partial-thickness
      rotator cuff tears who underwent acromioplasty, debridement of the abnormal
      tissue, and tendon suturing. Follow-up averaged 55 months (range 13 to 132
      months). Twenty-three (59%) patients had an excellent result, 10 (26%) patients
      had a satisfactory result, and 6 (15%) patients had an unsatisfactory result.
      Four of the six patients with unsatisfactory results had also had unsuccessful
      previous surgery. Thirty-five (90%) patients rated their response to surgery as
      either much improved or improved. No complications occurred, and to date no
      reoperations have been required. Diagnosis of partial-thickness rotator cuff
      tears can be challenging. Magnetic resonance imaging supplies the most complete
      information about tendon structure. Conservative treatment is reasonable for most
      partial-thickness tears. When surgical treatment is indicated, acromioplasty,
      debridement, and tendon repair are effective.

PMID- 8981270
TI  - Postoperative assessment of shoulder function: a prospective study of full
      thickness rotator cuff tears.
AB  - Forty patients underwent surgery by a single surgeon for chronic, symptomatic,
      full-thickness rotator cuff defects. The study evaluated preoperative and
      intraoperative factors that influence postoperative outcome. The study also
      correlated objective measures of shoulder function with postoperative symptoms,
      patient satisfaction, and disability. Follow-up history and physical examination
      and strength measurements were performed at 2 years after surgery by three
      independent observers. There were 88% good or excellent results. Postscores
      correlated most closely with preoperative tear size. Postoperative Constant
      scores also correlated significantly with the patient's subjective rating of the
      end result. Preoperative cuff tear size also correlated with the presence of
      postoperative fatigue symptoms and objective measures of shoulder strength.
      Preoperative cuff tear size strongly correlated with other prognostic factors
      including the quality of the tendon tissue, the difficulty for tendon
      mobilization, and the presence of a rupture of the long head of the biceps.
      Together these factors adversely affect postoperative function, patient
      satisfaction, and overall shoulder score. Neither premorbid activity level nor
      the presence of a worker's compensation claim adversely affected the
      postoperative Constant score. The premorbid activity level significantly
      influenced the postoperative disability rating and the ability to return to work.
      All patients who were gainfully employed before surgery returned to employment
      after surgery, although in some patients at a lesser activity level.

PMID- 8981273
TI  - Humeral bone density losses after shoulder surgery and immobilization.
AB  - This study evaluates disuse osteoporosis of the proximal humerus after shoulder
      surgery and immobilization. This was accomplished by quantifying bone mineral
      density changes in 22 patients' proximal humeri after 6 weeks of immobilization
      for soft-tissue shoulder surgery. The bone mineral density of the humeral head,
      neck, and proximal diaphyseal subregions was determined 1 to 2 weeks before
      surgery and at 3, 6, and 12 weeks after surgery with dual-energy x-ray
      absorptiometry. By the sixth postoperative week statistically significant bone
      mineral density decreases of 6% to 14% were observed in the humeral neck and head
      subregions, respectively. The changes in these three regions diminished slightly
      after 6 weeks of remobilization, but the differences were still statistically
      significant. No significant bone mineral density changes occurred in any
      subregion or during any time interval in the nonoperated humerus. Our study
      represents the first report with dual-energy x-ray absorptiometry to quantify
      bone loss of the proximal humerus of patients after shoulder immobilization.
      Further long-term study is warranted to determine the clinical significance of
      this bone loss and to determine whether these losses are partially or fully
      recoverable.

PMID- 8981274
TI  - Infections after surgical repair of acromioclavicular separations with
      nonabsorbable tape or suture.

PMID- 8981275
TI  - Use of an antibiotic-impregnated bone cement block in the revision of an infected
      shoulder arthroplasty.

PMID- 8981276
TI  - What is your diagnosis? Lethal acrodermatitis of English bull terriers.

PMID- 8981277
TI  - Distribution of Neospora caninum within the central nervous system and other
      tissues of six dogs with clinical neosporosis.
AB  - Six cases of neosporosis in dogs were diagnosed on the basis of clinical signs,
      serology and immunohistochemistry. The brains and spinal cords, at several
      levels, and various other tissues were examined using anti-Neospora caninum serum
      by an immunoperoxidase technique. Parasite density varied markedly from case to
      case. Although found most consistently in the cerebrum, parasites were
      distributed throughout the central nervous system (CNS), both within the grey and
      white matter and within nerve roots. Clinical signs were not related to the
      position of parasites. Tissue cysts were found infrequently in all areas of the
      CNS, but not in other tissues. Parasite density was not related to the age of the
      dog or whether treatment had been given. However, with the exception of the only
      adult dog examined, more CNS parasites were found in dogs with a longer duration
      of illness and with higher antibody titres. Tachyzoites were present in skeletal
      muscles, in the muscularis of the oesophagus, in heart, lung and, less
      frequently, liver, and rarely in the adrenal gland, thyroid gland and uterus; no
      clinical signs were seen resulting from damage to these organs. Parasites were
      not observed in lymphoid tissue. In visceral organs, parasites were most widely
      distributed in peracute cases. For post mortem diagnosis of neosporosis, the CNS,
      particularly the cerebrum, is the optimum tissue to examine but parasites may
      also be found in many other tissues, especially in acute cases. Muscle biopsy of
      appropriate muscles (as suggested by the clinical signs) provides the possibility
      of a definitive premortem diagnosis.

PMID- 8981278
TI  - Study of calcium homeostasis in feline hyperthyroidism.
AB  - Thirty cats with untreated hyperthyroidism were blood sampled and their calcium
      homeostatic mechanisms and renal function assessed. The results were compared
      with those obtained from 38 age-matched control cats. The hyperthyroid group of
      cats were found to have significantly lower blood ionised calcium and plasma
      creatinine concentrations and significantly higher plasma phosphate and
      parathyroid hormone concentrations. Hyperparathyroidism occurred in 77 per cent
      of hyperthyroid cats, with parathyroid hormone concentrations reaching up to 19
      times the upper limit of the normal range. The aetiology, significance and
      reversibility of hyperparathyroidism in feline hyperthyroidism remains to be
      established but could have important implications for both bone strength and
      renal function.

PMID- 8981279
TI  - Unusual metaphyseal disturbance in two kittens.
AB  - This report describes the presenting features, radiographic changes, biochemical
      alterations and clinical progress of two kittens, from separate litters, which
      were found to have a growth plate disturbance initially diagnosed and treated as
      vitamin D3-dependent rickets, but subsequently suspected to be a metaphyseal
      chondrodysplasia.

PMID- 8981280
TI  - Horner's syndrome associated with a functional thyroid carcinoma in a dog.
AB  - A seven-year-old entire male Irish setter was presented because of a neck mass,
      prolapse of the third eyelid and apparent drooping of the upper eyelid.
      Historical findings included increased appetite as well as polyuria and
      polydipsia for about two weeks. The most remarkable findings on physical
      examination were right-sided Horner's syndrome, pre-scapular lymphadenopathy and
      a large, ventral cervical mass. Lateral cervical radiographs showed a large, soft
      tissue opacity surrounding the trachea and retropharyngeal area which was causing
      displacement and narrowing of the cervical trachea and oesophagus. Results of
      thyroid testing suggested hyperthyroidism. At necropsy, a large, invasive tumour
      was identified in the ventral cervical region and multiple metastases of various
      sizes were detected in the lungs. Histopathological examination of the tumour
      revealed follicular thyroid carcinoma and confirmed widespread pulmonary
      metastasis.

PMID- 8981282
TI  - Veterinary sites on the Internet and the World Wide Web.

PMID- 8981283
TI  - Case of calcifying epithelial odontogenic tumour in a dog.
AB  - A 12-year-old male shih tzu dog was diagnosed as having a calcifying epithelial
      odontogenic tumour. One and a half years prior to presentation, a mass was
      noticed on the right mandible by the owners. Radiography revealed irregular,
      faintly radiopaque material within the tumour. A right hemimandibulectomy was
      performed, based on the clinical diagnosis of osteosarcoma. Histopathological
      evaluation of the mandibular mass showed that it was composed of a polyhedral
      odontogenic epithelial cell nest, fibrous stroma, homogeneous eosinophilic
      material and rounded calcifying material. The eosinophilic material was
      visualised by staining with Congo red, and observed under green birefringence by
      polarisation microscopy. Although the tumour had not recurred 12 months after
      surgery, the dog was euthanased because of aspiratic pharyngitis. The literature
      on the clinical behaviour of calcifying epithelial odontogenic tumours in dogs
      and cats is reviewed.

PMID- 8981281
TI  - Hypovolaemic shock after anthelmintic treatment of canine angiostrongylosis.
AB  - Canine angiostrongylosis was diagnosed in a whippet with typical signs of
      respiratory and circulatory distress. Subclinical Angiostrongylus vasorum
      infections were also demonstrated in two other whippets belonging to the same
      owner. All three dogs were given standard anthelmintic levamisole treatment
      combined with corticosteroids. Two days after initiation of treatment, one of the
      subclinically infected dogs developed severe hypovolaemic shock that required
      intravenous fluid therapy and corticosteroids to save its life. The shock is
      believed to have been caused by an anaphylactic reaction triggered by the rapid
      release of a large amount of worm antigen in the blood due to the rapid death of
      adult worms by levamisole. Thus, dog owners should be instructed to monitor dogs
      undergoing levamisole treatment against A vasorum. Alternatives to levamisole
      treatment of canine angiostrongylosis should be considered.

PMID- 8981284
TI  - Destructive polyarthritis in a dog with leishmaniasis.
AB  - The clinical history and diagnosis of a dog with leishmaniasis involving both
      elbow joints and the skin is described. The dog, a female, five-year-old
      crossbreed, had been imported from Majorca (Balearic Islands, Spain) four years
      before the diagnosis was made. For two years, the dog had had bilateral forelimb
      lameness. Physical examination revealed swollen, painful and crepitating elbow
      joints. Furthermore, an ulcerating dermatitis was found on the concave surface of
      the left pinna and necrotising margins on both ears. Radiographs of the elbow
      joints revealed complete destruction of the joint surfaces with dislocation of
      the radius and the ulna, compatible with severe osteolytic arthritis. The
      diagnosis of leishmaniasis was confirmed by a direct agglutination test.

PMID- 8981285
TI  - Scientific information document Helicobacter pylori.

PMID- 8981286
TI  - Threat and coping appraisal as determinants of compliance with sports injury
      rehabilitation: an application of Protection Motivation Theory.
AB  - The aim of this study was to examine the effects of threat appraisal (perceived
      susceptibility to re-injury or retarded rehabilitation and perceived severity of
      injury) and coping appraisal (self-efficacy, treatment efficacy and outcome
      value), in the framework of Protection Motivation Theory (PMT), on compliance to
      a sports physiotherapist's prescribed modalities and rest. During extensive
      developmental work, a Sports Injury Rehabilitation Beliefs Survey was constructed
      with 19 items to assess the PMT components. Five compliance measures were
      developed from physiotherapist and patient surveys. Data from 62 subjects (68%
      female, mean +/- S.D. age 21.7 +/- 2.85 years, and involved in many recreational
      and competitive activities) were obtained from a single university-based sports
      injury clinic, in a prospective study. The study revealed that over half the
      subjects were subsequently non-compliant to some degree. Greater perceptions of
      both susceptibility to retarded rehabilitation and injury severity, at the first
      appointment, were related to subsequent non-compliant behaviour. Greater self
      efficacy in the ability to perform prescribed rehabilitation modalities, stronger
      beliefs in the treatment efficacy, and higher value attached to rehabilitation,
      were all related to compliant behaviour. Compliance to restricted activity (or
      rest) was only related to greater perceptions of susceptibility. The findings
      provide some support for PMT in this context and offer a basis for designing
      sports therapist interventions which focus on threat and coping appraisal.

PMID- 8981287
TI  - Dynamics of the martial arts high front kick.
AB  - Fast unloaded movements (i.e. striking, throwing and kicking) are typically
      performed in a proximo-distal sequence, where initially high proximal segments
      accelerate while distal segments lag behind, after which proximal segments
      decelerate while distal segments accelerate. The aims of this study were to
      examine whether proximal segment deceleration is performed actively by antagonist
      muscles or is a passive consequence of distal segment movement, and whether
      distal segment acceleration is enhanced by proximal segment deceleration.
      Seventeen skilled taekwon-do practitioners were filmed using a high-speed camera
      while performing a high front kick. During kicking, EMG recordings were obtained
      from five major lower extremity muscles. Based on the kinematic data, inverse
      dynamics computations were performed yielding muscle moments and motion-dependent
      moments. The results indicated that thigh deceleration was caused by motion
      dependent moments arising from lower leg motion and not by active deceleration.
      This was supported by the EMG recordings. Lower leg acceleration was caused
      partly by a knee extensor muscle moment and partly by a motion-dependent moment
      arising from thigh angular velocity. Thus, lower leg acceleration was not
      enhanced by thigh deceleration. On the contrary, thigh deceleration, although not
      desirable, is unavoidable because of lower leg acceleration.

PMID- 8981288
TI  - Effect of water ingestion on endurance capacity during prolonged running.
AB  - This study examined the influence of water ingestion on endurance capacity during
      submaximal treadmill running. Four men and four women with a mean (+/-S.E.) age
      of 21.4 +/- 0.7 years, height of 169 +/- 2 cm, body mass of 63.1 +/- 2.9 kg and
      VO2 max of 51.1 +/- 1.8 ml kg-1 min-1, performed two randomly assigned treadmill
      runs at 70% VO2 max to exhaustion. No fluid was ingested during one trial (NF
      trial), whereas a single water bolus of 3.0 ml kg-1 body mass was ingested
      immediately pre-exercise and serial feedings of 2.0 ml kg-1 body mass were
      ingested every 15 min during exercise in a fluid replacement trial (FR-trial).
      Run time for the NF-trial was 77.7 +/- 7.7 min, compared to 103 +/- 12.4 min for
      the FR-trial (P < 0.01). Body mass (corrected for water ingestion) decreased by
      2.0 +/- 0.2% in the NF-trial and 2.7 +/- 0.2% in the FR-trial (P < 0.01), while
      plasma volume decreased by 1.1 +/- 1.1% and 3.5 +/- 1.1% in the two trials
      respectively (N.S.). However, these apparent differences in circulatory volume
      were not associated with differences in rectal temperature. Respiratory exchange
      ratios indicated increased carbohydrate metabolism (73% vs 64% of total energy
      expenditure) and suppressed fat metabolism after 75 min of exercise in the NF
      trial compared with the FR-trial (NF-trial, 0.90 +/- 0.01; FR-trial, 0.86 +/-
      0.03; P < 0.01). Blood glucose concentrations were similar in both trials, while
      blood lactate concentrations were higher in the NF-trial at the end of exercise
      (4.83 +/- 0.34 vs 4.18 +/- 0.38 mM; P < 0.05). In summary, water ingestion during
      prolonged running improved endurance capacity.

PMID- 8981289
TI  - The interpretation of relative momentum data to assess the contribution of the
      free limbs to the generation of vertical velocity in sports activities.
AB  - The contribution that the free limbs (the arms and lead leg) make to vertical
      velocity at take-off during jumping activities was determined by using a relative
      momentum approach. This requires the momentum of each free limb to be quantified
      relative to the joint at which the limb is attached to the body between the
      touchdown (or start of movement) and the take-off. The contribution that each
      makes to the vertical velocity at take-off requires interpretation of the
      momentum data. It has been shown that two interpretations cited in the literature
      pose difficulties, and a third is offered. This interpretation is that: (1) the
      contribution of a single limb to vertical velocity at take-off is determined by
      the increase in the positive relative momentum value between the beginning
      (touchdown) and end (take-off) of the action; (2) when considering a single limb,
      the negative relative momentum can be ignored as it makes no direct contribution
      to upward movement; and (3) the contribution of relative momentum for a number of
      limbs together is the increase in the positive value of the sum of the relative
      momentum for all limbs between the start and end of the action. This
      interpretation was applied to a counter-movement vertical jump and a running
      stride. In the counter-movement jump, the arms were found to produce a relative
      momentum of 30.9 N s, which was 12.7% of the peak total body vertical momentum.
      In running, the arms produced a relative momentum of 3.75 N s, which corresponded
      to 6.4% of the peak total body vertical momentum, while the arms and lead leg
      combined produced a peak value of 2.45 N s, which corresponds to a contribution
      of 4.2%. We conclude that the proposed interpretation enabled sensible
      estimations to be made of the contribution of the arms to jumping performance.

PMID- 8981290
TI  - Optimized and corrected peak power output during friction-braked cycle ergometry.
AB  - Assessments of maximal intensity exercise which determine peak power output on
      friction-baked cycle ergometers have fallen into two categories: correction
      procedures which account for changes in momentum of the ergometer's flywheel and
      optimization procedures which attempt to satisfy muscle force-velocity
      relationships. The aim of this study was to compare performance in each procedure
      and so investigate assumptions which underpin the tests. Nineteen males aged 20.9
      +/- 0.4 years and 18 females aged 22.2 +/- 0.7 years (mean +/- S.E.M.), who were
      fully accustomed to the procedures, participated in a single experimental
      protocol. After a 5 min warm-up, the subjects performed four bouts of all-out
      exercise on a Monark 814E cycle ergometer against randomly assigned loads. The
      loads were selected to produce peak pedalling rates in the range 100-200 rev min
      1 and each bout lasted 10 s. From the inverse linear relationship between applied
      load and peak pedalling rate, optimized peak power output (PPopt) and the
      accompanying pedalling rate (RPMopt) were calculated. One of the bouts used a
      loading equivalent to 7.5% of body weight and for this bout corrected peak power
      output (PPcorr) and its corresponding pedalling rate (RPMcorr) were calculated.
      The PPopt was less than PPcorr in the males (915 +/- 35 vs 1005 +/- 32 W) and
      females (673 +/- 33 vs 777 +/- 39 W) (both P < 0.001). Similarly, RPMopt was less
      than RPMcorr (111 +/- 1 vs 128 +/- 2 rev min-1 and 101 +/- 1 vs 111 +/- 2 rev min
      1 in the males and females, respectively; P < 0.001). The results demonstrate
      that optimization and correction procedures produce different values of
      performance. These differences are probably attributable to the mechanical
      principles which underpin the tests.

PMID- 8981291
TI  - Analysis and modification of verbal coaching behaviour: the usefulness of a data
      driven intervention strategy.
AB  - This study tested a computer-aided coaching analysis instrument (CAI) as part of
      an intervention strategy designed to modify verbal coaching behaviour. Four
      coaches were observed and analysed over 12 practice sessions. Coaches A, B and C
      received intervention feedback through CAI data, where selected behaviours were
      highlighted for discussion, and videotape images were used to illustrate
      discussion points. Coach D was provided with videotapes of his own performance
      and told to formulate and implement any of his own recommendations. The CAI data
      are primarily quantitative, so target values were created for the different
      dimensions of verbal behaviour. This benefited the coaches in interpreting their
      effectiveness and provided a reference to evaluate the magnitude of change.
      Written journals and audiotape recordings were also used to promote insight into
      the complexity of verbal behaviour and the "human factors' (e.g. relationship
      with players, attitude to researcher) that affect behaviour modification.
      Instructional effectiveness was assessed by time-series analysis. There was
      evidence from each behaviour dimension that change can occur and be maintained as
      a result of exposure to the CAI intervention strategy. However, this is clearly
      contingent upon the coach understanding what is asked of him or her, and remains
      focused and committed to changing these particular behaviours. The analysis of
      Coach D's behavioural change suggests there are limitations to the sensitivity of
      discretionary viewing, as only two dimensions of behaviour were identified for,
      and resulted in, positive change. The results of this study provide support for
      Locke's (1984) contention that behaviour modification can occur by using data as
      direct feedback, as reinforcement and as information in the form of
      recommendations. However, the study also illuminates several factors that can
      negate the modification and maintenance of verbal coaching behaviour.

PMID- 8981293
TI  - Suppression of experimental autoimmune neuritis by phosphodiesterase inhibitor
      pentoxifylline.
AB  - Phosphodiesterase inhibitor pentoxifylline (POX) has been shown to have multiple
      immunomodulatory effects in vitro and in vivo. It inhibits T cell proliferation,
      T helper 1-type cytokines, and tumor necrosis factor. We postulated that POX
      might have an in vivo immunomodulatory effect on a T-cell-mediated autoimmune
      peripheral nervous system disease, experimental autoimmune neuritis (EAN). We
      investigated the effect of POX on EAN in rats immunized with peripheral nerve
      myelin containing neuritogenic peptide SP26. At 200 mg/kg/day, there was
      significant suppression of clinical EAN, weight loss, and T cell proliferation to
      SP26 compared to controls. Proliferation of T cells from immunized rats to SP26
      was suppressed by POX in vitro. These studies demonstrate a beneficial role for
      POX in EAN, with potential applicability to human autoimmune demyelination.

PMID- 8981292
TI  - European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the
      secondary prevention of stroke.
AB  - In 1988, we undertook a randomized, placebo-controlled, double-blind trial to
      investigate the safety and efficacy of low-dose acetylsalicylic acid (ASA),
      modified-release dipyridamole, and the two agents in combination for secondary
      prevention of ischemic stroke. Patients with prior stroke or transient ischemic
      attack (TIA) were randomized to treatment with ASA alone (50 mg daily), modified
      release dipyridamole alone (400 mg daily), the two agents in a combined
      formulation, or placebo. Primary endpoints were stroke, death, and stroke or
      death together. TIA and other vascular events were secondary endpoints. Patients
      were followed on treatment for two years. Data from 6,602 patients were analysed.
      Factorial analysis demonstrated a highly significant effect for ASA and for
      dipyridamole in reducing the risk of stroke (p < or = 0.001) and stroke or death
      combined (p < 0.01). In pairwise comparisons, stroke risk in comparison to
      placebo was reduced by 18% with ASA alone (p = 0.013); 16% with dipyridamole
      alone (p = 0.039); and 37% with combination therapy (p < 0.001). Risk of stroke
      or death was reduced by 13% with ASA alone (p = 0.016); 15% with dipyridamole
      alone (p = 0.015); and 24% with the combination (p < 0.001). The treatment had no
      statistically significant effect on the death rate alone. Factorial analysis also
      demonstrated a highly significant effect of ASA (p < 0.001) and dipyridamole (p <
      0.01) for preventing TIA. The risk reduction for the combination was 36% (p <
      0.001) in comparison with placebo. Headache was the most common adverse event,
      occurring more frequently in dipyridamole-treated patients. All-site bleeding and
      gastrointestinal bleeding were significantly more common in patients who received
      ASA in comparison to placebo or dipyridamole. We conclude that (1) ASA 25 mg
      twice daily and dipyridamole, in a modified-release form, at a dose of 200 mg
      twice daily have each been shown to be equally effective for the secondary
      prevention of ischemic stroke and TIA; (2) when co-prescribed the protective
      effects are additive, the combination being significantly more effective than
      either agent prescribed singly; (3) low-dose ASA does not eliminate the
      propensity for induced bleeding.

PMID- 8981295
TI  - Vascular dementia: still a debatable entity?
AB  - Vascular dementia (VAD) is currently considered to be the second most common
      cause of dementia in Europe and the USA, second to dementia of the Alzheimer's
      type (DAT). However, in Asia and many developing countries the incidence of VAD
      exceeds that of DAT. The positive clinical diagnostic workup for VAD requires six
      steps: (1) clear-cut quantitative assessment of cognitive deficits utilizing
      standard neuropsychological tests to establish and quantify the dementia syndrome
      and rule out pseudo-dementia OF depression; (2) ascertaining the presence of risk
      factors for stroke; (3) identifying cerebral vascular lesions by neuroimaging
      (MRI, Iodine or Xenon contrasted CT, PET and SPECT); (4) exclusion of other
      causes of dementia; (5) differential diagnosis of possible, probable or definite
      VAD versus DAT and ascertaining when there are mixtures of the two; and (6)
      temporal identification of causality between onset and progression of the
      dementia with identified cerebral vascular lesions. There are eight subtypes of
      VAD: (1) multi-infarct dementias. These are due to large cerebral emboli, and are
      usually readily identifiable; (2) strategically placed infarctions causing
      dementia; (3) multiple subcortical lacunar lesions. Patients with these develop
      VAD at least five to twenty-five times more frequently than those in age-matched
      general population samples; (4) Binswanger's disease (arteriosclerotic
      subcortical leuko-encephalopathy). This form is rare. Neuroimaging confirms the
      diagnosis during life but the diagnosis can not be made by neuroimaging alone;
      (5) mixtures of two or more of above VAD subtypes; (6) hemorrhagic lesions
      causing dementia; (7) subcortical dementias due to cerebral autosomally dominant
      arteriolopathy with subcortical infarcts and leuko-encephalopathy (CADASIL), or
      to familial amyloid angiopathies and coagulopathies all of which present with
      multiple subcortical lacunar lesions similar to Binswanger's disease; (8)
      mixtures of DAT and VAD. The clinical significance of leukoaraiosis and its
      suspected relationships to VAD remains to be better established. The presence of
      ischemic infarctions, single or multiple large or multiple small (lacunar) by
      neuroimaging are necessary for the diagnosis of VAD, but identifying their
      presence, by neuroimaging alone, does not permit the diagnosis of dementia which
      can only be established by neuropsychological assessments. VAD is a clinical
      entity, identifiable in at least 30-70% of patients after strokes but mechanisms
      responsible for the cognitive impairments are complex. Some of these mechanisms
      are incompletely understood but provide subjects for important future research.

PMID- 8981294
TI  - Rhinocerebral and systemic mucormycosis. Clinical experience with 36 cases.
AB  - We analysed retrospectively our clinical experience with 36 cases of
      mucormycosis. They were seen during the last 15 years. The diagnosis suspected on
      clinical grounds, was confirmed in 31 cases by finding the hyphae in hematoxylin
      eosin stained material obtained from aspirated or tissue biopsy or by isolation
      of the fungus in culture. Rhinocerebral mucormycosis was diagnosed in 22
      patients. Diabetes was the underlying disorder in 20 cases, kidney failure in one
      and myelodysplastic syndrome in one. Nine had stable and 11 unstable diabetes
      (ketoacidosis in 10 and hyperosmolar coma in 1). The earliest sign was facial
      edema, followed by proptosis, chemosis and extraocular muscle paresis. They were
      treated by extensive surgical debridement, insulin and antifungal drugs with 69%
      of survival rate. The disseminated mucormycosis was diagnosed at the autopsy in 5
      cases, acute leukemia was the underlying disease in 2 of them. Pulmonary
      mucormycosis was diagnosed in 2 cases, cutaneous form in 2, sinuorbital form in 4
      and brain abscess in one patient. Eight of these 9 cases survived after therapy.
      We emphasize the importance of an early diagnosis. This can only be made in the
      presence of a typical clinical setting confirmed by finding the hyphae in tissue
      or culture. Antifungal drugs along with treatment of the underlying disorder and
      aggressive surgical debridement must follow.

PMID- 8981296
TI  - Mitochondrial encephalopathy with multiple mitochondrial DNA deletions: a report
      of two families and two sporadic cases with unusual clinical and
      neuropathological features.
AB  - A mitochondrial myopathy associated with multiple deletions of mitochondrial DNA
      has been identified in pedigrees showing an autosomal dominant mode of
      inheritance. We report the first two British kindreds with this disorder, and two
      sporadic cases. The families exhibited some unusual clinical features, including
      pigmentary retinopathy and tremor; the latter was levodopa-responsive and
      associated with rigidity and micrographia in one family. Members of one pedigree
      and both sporadic patients had a peripheral neuropathy and nerve biopsy showed
      marked axonal degeneration. Post-mortem examination of one patient without
      parkinsonism showed severe neuronal loss in the substantia nigra.

PMID- 8981297
TI  - Calf enlargement in neuromuscular diseases: a quantitative ultrasound study in
      350 patients and review of the literature.
AB  - Calf hypertrophy is a typical clinical feature in neuromuscular diseases such as
      X-linked muscular dystrophies of Duchenne and Becker type and can be seen as an
      atypical feature in numerous other diseases. The diagnosis of calf hypertrophy
      usually is based on subjective visual assessment. The aim of this prospective
      study was to examine the prevalence of calf hypertrophy in a large number of
      patients with various neuromuscular diseases based on quantitative ultrasound
      measurement of calf muscle thickness. Additionally, true and pseudohypertrophy
      should be distinguished according to the absence or presence of abnormal muscle
      echointensities caused by infiltration of fat tissue. Fifty adult normal controls
      and 350 patients with various neuromuscular diseases were investigated. Absolute
      calf hypertrophy was diagnosed if the combined thickness of the gastrocnemius and
      soleus muscles exceeded the mean value of the control persons by at least 3.0
      standard deviations (SD). Relative calf hypertrophy was diagnosed when the ratio
      of the combined thicknesses of the gastrocnemius and soleus muscles divided by
      the combined thicknesses of the rectus femoris and vastus intermedius muscles lay
      at least 3.0 SD below the mean value of the controls. Pseudohypertrophy was
      present if the echointensities of the gastrocnemius and soleus muscles reached or
      exceeded 3.0 SD above the mean value of the controls. An absolute hypertrophy of
      the calves was detected in 80 patients (= 22,9%; 64 true and 16
      pseudohypertrophies), 16 patients exhibited a relative hypertrophy of the calves
      (= 4.6%; 12 true and 4 pseudohypertrophies). A significantly increased portion of
      both absolute calf hypertrophies and pseudohypertrophies as compared to the
      control group were found in juvenile proximal spinal muscular atrophy type 3,
      central core disease, centronuclear myopathy, benign X-linked muscular dystrophy
      of Becker type, autosomal recessive limb girdle muscular dystrophy, acid maltase
      deficiency, polymyositis, and granulomatous myositis. A significantly increased
      number of relative calf hypertrophies was present in juvenile proximal spinal
      muscular atrophy type 3, facioscapulohumeral muscular dystrophy, and inclusion
      body myositis. In the majority of the diseases included in the study, calf
      hypertrophy occurred in at least some patients. In conclusion, calf hypertrophy
      is a frequent and unspecific clinical feature in many neuromuscular diseases.
      Ultrasound is a convenient method for the exact definition of calf hypertrophy.

PMID- 8981298
TI  - Anti-gabaergic neuron autoantibodies in a patient with stiff-man syndrome and
      ataxia.
AB  - We describe a patient with autoimmune insulin-dependent diabetes whose original
      symptoms of trunk stiffness and rigidity of the abdomen were followed three years
      later by a pancerebellar syndrome. An autoantibody (autoAb) against GABAergic
      neurons was found in the patient's serum and cerebrospinal fluid (CSF); on
      Western blot, this autoAb recognized a 64-kDa antigen of cerebellar protein. The
      detection of this antibody in a case with ataxia suggests that a spectrum of
      different neurological diseases may be observed in patients harbouring anti
      GABAergic neuron autoAb and supports the concept that factors other than autoAb
      contribute to the clinical presentation of these disorders.

PMID- 8981299
TI  - Effects of the calcium channel blockers Dotarizine and Flunarizine on
      cerebrovascular reactivity.
AB  - Dotarizine and Flunarizine are piperazine derivatives considered to be effective
      compounds for the treatment of various cerebrovascular disorders. In the present
      study the influence of these two drugs on changes in cerebral vessel diameter and
      blood flow velocity were measured and compared utilising transcranial Doppler
      sonography during hyperventilation in anaesthetized cats. Drugs were administered
      in 15 min intravenous infusions at a dose of 0.05 mg/kg/min. This investigation
      revealed that the 15 min intravenous administration of both compounds abolished
      the cerebral vasoconstrictor effects of hyperventilation and due to vasodilator
      effects they increased blood flow velocity to initial values. No statistically
      significant differences were found between the vasodilator effects of Dotarizine
      and Flunarizine. Results obtained suggest that Dotarizine, a novel piperazine
      derivative, has similar vasodilator and Ca2+ channel blocking effects on
      cerebrovascular reactivity compared to the widely clinically applied Flunarizine.

PMID- 8981300
TI  - Parkinson's disease, cognition and aging. Clinical, neuropsychological,
      electrophysiological and cranial computerized tomographic assessment.
AB  - Forty-three patients with Parkinson's disease (PD) and thirty-seven normal
      volunteers were subjected to clinical, neuropsychological, neurophysiological
      (P300 component of the event-related potentials ERP) and radiological (cranial
      computerized tomographic scanning CCT) evaluation. Intentional memory was more
      impaired in PD than in normal controls, more so in the demented group of
      patients, and was related to enlargement of third ventricular size in CCT. While
      intentional memory was age related in PD patients, perception was age-related in
      normal controls. Neither global nor specific cognitive functions were related to
      duration, severity of parkinsonian motor disability, or depression. However,
      depression in PD was significantly related to parkinsonian motor disability. P300
      latency was more prolonged in PD patients than normal controls. P300 parameters
      of PD patients were not influenced by age, cognitive functions, duration or
      severity of motor disability, or depression. The reaction time was the only P300
      parameter that was age-related in normal controls. Subcortical atrophy as
      indicated by CCT was more marked in PD and correlated with age in both patients
      and controls. Subcortical atrophy was significantly related to cognitive
      functions in PD but not in normal controls. It was concluded that cognitive
      impairment in PD could be attributed to complex cognitive changes rather than
      age. It is a disease process, though not directly related to parkinsonian motor
      disability or depression. PD differed from normal aging as regards the effect of
      age on the specific cognitive functions, where in PD patients, age was related to
      intentional memory, yet in normal controls, it was related to perception.
      Intentional memory deterioration was found to be specific of PD, being related to
      subcortical atrophy as well as being more pronounced in the demented group of
      patients.

PMID- 8981301
TI  - Relationships between delayed ischemic dysfunctions and intracranial hemodynamics
      following subarachnoid hemorrhage.
AB  - Delayed ischemic dysfunctions (DID) are one of the main complications following
      subarachnoid hemorrhage. It was the aim of our study to analyse the possible
      prognostic value of different transcranial Doppler ultrasonography parameters and
      to elucidate the risk of developing DID with particular reference to the
      intracranial pressure. The relative change of mean blood flow velocity and of
      corresponding cerebral circulatory resistance index as well as the intracranial
      pressure were determined in 44 patients with spontaneous subarachnoid hemorrhage.
      No relationship was found between the occurrence and extent of DID and the
      relative change of mean flow velocity during the clinical course. In contrast,
      there was a significant correlation between the relative change of the cerebral
      circulatory resistance index and the occurrence of DID. While patients without or
      with reversible DID showed a decreased resistance index compared to the initial
      value (without DID: -17% +/- 15%; reversible DID: -3% +/- 14%), patients with
      irreversible DID had a significant increase of the resistance index (+14% +/-
      9%). Accordingly, patients with irreversible DID showed a significant increase of
      intracranial pressure compared to the patients with reversible DID. We conclude
      that the evaluation of relative changes of the cerebral circulatory resistance
      index by bedside monitoring is a useful tool to predict the occurrence of
      subarachnoid hemorrhage-associated DID and has therapeutic impact.

PMID- 8981302
TI  - Characteristic expression of cell adhesion molecules in adhalin deficiency.
AB  - We have reported the reduction of the B1 subunit of laminin and that of heparan
      sulfate proteoglycan (HSPG) in two Japanese patients with adhalin deficiency. We
      here investigated immunohistochemically the expression of cell adhesion
      molecules, including intercellular adhesion molecule-1 (ICAM-1), neural cell
      adhesion molecule (NCAM), and CD44 (HCAM), in four Japanese patients with adhalin
      deficiency, compared to other types of muscular dystrophy. We found that NCAM was
      upregulated in a fair number of muscle fibers, regardless of the type of muscular
      dystrophy. ICAM-1 was detected on the rare muscle cell membrane in all patients.
      CD44 was barely detected on the muscle cell membrane in adhalin deficiency, in
      contrast to the strong expression of CD44 which was observed in other types of
      muscular dystrophy. These findings suggest that a different degenerative or
      regenerative process is involved in adhalin deficiency compared to other types of
      muscular dystrophy.

PMID- 8981303
TI  - Trigemino-cervical reflexes in normal subjects.
AB  - Trigemino-cervical reflexes, recorded from the semispinalis capitis muscle (SCM)
      in the posterior neck, were studied in 35 healthy volunteers, in response to
      electrical stimulation of the supraorbital trigeminal nerve and glabellar
      tapping. Simultaneous responses evoked from the ipsilateral orbicularis oculi
      muscle (OOM) were also recorded i.e. blink reflexes. Electrical stimulation of
      the supraorbital nerve elicited a reflex response with a latency of about 50 ms
      from the ipsilateral SCM which was called C3. An early reflex response, which
      sometimes had two components with latencies of 18 ms and 35 ms, was elicited with
      glabellar taps. They were called C1 and C2 respectively. When C1 and C2 were
      elicited with usual glabellar taps, C3 was suppressed. With electrical
      stimulation, suppression of C1 and C2 was noted, though C3 could easily be
      obtained. Electrophysiological characteristics of C1 (and C2) were compatible
      with an oligosynaptic, innocuous reflex, whereas C3 seemed to be multisynaptic
      and nociceptive in nature. A negative interaction between these two reflexes was
      observed.

PMID- 8981305
TI  - Micturitional disturbance in syringomyelia.
AB  - Micturitional histories and urodynamic studies were performed in 14 patients with
      syringomyelia. Eleven patients were revealed to have urinary symptoms including
      difficulty of voiding in 8, urinary retention in 3, nocturnal and diurnal urinary
      frequency in 3, urinary incontinence in 2, and sense of urgency and enuresis in
      one. These urinary symptoms appeared after 5.3 years (ranging from 2 months to 13
      years) from the occurrence of the neurological symptoms. Urodynamic studies
      revealed detrusor hyperreflexia in 7, detrusor areflexia in 4, detrusor-sphincter
      dyssynergia in 4 and uninhibited sphincter relaxation in 2 patients. Analysis of
      the motor unit potentials of the external sphincter revealed 5 of 6 patients had
      high amplitude or polyphasic neurogenic changes. Supranuclear as well as nuclear
      types of parasympathetic and somatic nerve dysfunctions seemed to be responsible
      for micturitional disturbance in our patients with syringomyelia. During the
      follow-up period of 2 to 63 months, urinary symptoms gradually improved in 4 of 6
      patients after syringosubarachnoid shunts and in 3 of 4 after alpha
      adrenoreceptor blocking agents.

PMID- 8981304
TI  - Systemic high-dose recombinant-alpha-2a-interferon therapy modulates lymphokine
      production in multiple sclerosis.
AB  - Chronic systemic high-dose recombinant alpha 2a-interferon (rIFNA) therapy
      reduces exacerbation rate and MRI signs of disease activity in
      relapsing/remitting multiple sclerosis (RR MS) patients. In order to clarify the
      possible mechanisms underlying the clinical efficacy of rIFNA in MS, several
      immunologic studies were performed as a part of a pilot clinical trial. Twenty RR
      MS patients were treated with 9 x 10(6) IU of rIFNA (n = 12) or placebo (n = 8)
      intramuscularly every other day for 6 months. Cytokine production by cultured
      lymphocytes, major histocompatibility complex class II (MHC-II) antigen
      expression on cultured macrophages, peripheral blood (PB) and cerebrospinal fluid
      (CSF) lymphocyte phenotype, and IgG and beta 2 microglobulin levels were studied
      before therapy, after 6 months of therapy, and 6 months after stopping therapy.
      rIFNA therapy was associated with reduction of interferon-gamma and tumor
      necrosis factor-alpha production by PB lymphocytes (p < 0.04), and with slight,
      not significant, increase of transforming growth factor-beta 2 or interleukin
      (IL)-10 production. IL-4 was undetectable in the culture supernatants both before
      and after therapy. rIFNA therapy had no effect on macrophage MHC-II molecule
      expression. An increased percentage of CD8+, CD8+ high CD11b+ low, and CD3- CD16+
      CD56+ cells, and of CD4+ absolute cell number was observed in CSF after rIFNA
      therapy. After rIFNA administration, IgG level significantly increased both
      systemically (p < 0.02) and intrathecally (p < 0.001). Serum beta 2 microglobulin
      level increased (p < 0.01), as well. Only 1 out of the 12 rIFNA treated patients
      developed neutralizing antibodies against rIFNA during therapy. Six months after
      stopping therapy all the immunologic changes returned to baseline. These data
      suggest that the beneficial effect of rIFNA therapy on MS disease activity is
      probably mediated by a downregulation of proinflammatory cytokine synthesis by PB
      lymphocytes rather than by macrophage MHC-II antigen expression. The immunologic
      effects of high-dose systemic rIFNA therapy are temporary and restricted to the
      period of drug administration.

PMID- 8981306
TI  - Serum IgG to brain microvascular endothelial cells in multiple sclerosis.
AB  - Serum IgG to brain microvascular endothelial cells (BMECs) were assessed in the
      sera from 50 patients with definite multiple sclerosis, 24 patients with other
      inflammatory and non-inflammatory neurological diseases and 30 healthy
      individuals. Standard indirect immunofluorescence on BMEC culture was used as the
      bioassay system. Positive immunostaining was found in the sera (1:5 to 1:50
      dilution) from 0/15 inactive relapsing remitting (RR), 12/16 active RR (p =
      0.0001), 1/8 relapsing progressive (RP) and 0/11 primary progressive (PP)
      patients. No specific binding was detected when sera from neurologic and healthy
      controls were used. The specificity of the immune reaction for brain endothelium
      was established by the absence of staining on human umbilical vein endothelial
      cell and brain pericyte cultures. Gadolinium (Gd)-enhanced magnetic resonance
      imaging of the brain and spinal cord was performed in 36 MS patients within a 10
      day interval from serum collection. Anti-brain endothelium antibodies were found
      in 9/12 patients with, and in 1/24 patients without Gd-enhanced lesions (p =
      0.00002). Regardless of a pathogenetic role in the blood-brain barrier breakdown,
      serum IgG to BMECs may be a marker of disease activity in RR and RP MS and a
      factor differentiating RR/RP and PP MS.

PMID- 8981307
TI  - Tropical spastic paraparesis and HTLV-I infection: clinical and epidemiological
      study in Lima, Peru.
AB  - A descriptive study was performed to investigate the epidemiology and clinical
      features of 50 patients with tropical spastic paraparesis (TSP) associated with
      HTLV-I infection acquired in Peru. Cases seen at two reference centers in Lima
      (Alexander von Humboldt Tropical Medicine Institute and Guillermo Almenara
      National Hospital) between August 1989 and December 1995 are reviewed. All
      patients had serologic evidence of infection with reactive ELISA tests for HTLV
      I, confirmed by positive Western blot assays. The male-female ratio of cases was
      1.0:1.78. The mean age at the time of diagnosis was 52.4 years (range: 29 to 73,
      SD:11.3). A considerable proportion of patients (68%) had lived in Andean
      regions: this basically due to their native places (48%) because only 8% of cases
      were referred from these regions. The mean duration of symptoms prior to
      diagnosis was 4.95 years (range 0.5-22 years). The clinical features at diagnosis
      included progressive spastic paraparesis (100%) associated with sphincter
      disturbances (77.7%), paresthesia (61.1%) or lumbar pain (44%). The functional
      status of all patients was impaired at the time of evaluation: 44.1% walked
      unaided with a 'scissors-like' gait, 38% used assist devices for walking, 10%
      used wheelchairs and 8% were bedridden.

PMID- 8981308
TI  - Serum Cu/Zn superoxide dismutase activity is reduced in sporadic amyotrophic
      lateral sclerosis patients.
AB  - Accumulated evidence implies that mutations in the gene coding for Cu/Zn
      superoxide dismutase (SOD) are associated with the pathogenesis of the familial
      form of amyotrophic lateral sclerosis (ALS). The clinical and pathological
      similarities of the familial and the sporadic forms of the disease may suggest
      that abnormal SOD activity takes also part in the pathogenesis of sporadic ALS.
      We therefore measured serum SOD activity in fifteen sporadic ALS patients. Mean
      serum SOD activity was 1.15 +/- 0.40 u/ml in ALS patients, 1.50 +/- 0.45 u/ml. in
      patients with other neurological disorders and 1.45 +/- 0.45 u/ml in.healthy
      controls (p < 0.021 and p < 0.031 respectively). If this sporadic ALS-related
      reduction in serum SOD activity will be confirmed in the diseased nervous system
      tissue, it may suggest that abnormal SOD activity is also associated with the
      motor neuron damage in the sporadic form of ALS.

PMID- 8981309
TI  - Muscarinic, N-methyl-D-aspartate (NMDA) and benzodiazepine receptor binding sites
      in cortical membranes from amyotrophic lateral sclerosis patients.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      causing marked pathology in the motoneuron system. The pathophysiology of the
      selective degeneration of motor neurons in the disease is as yet unknown, but
      evidence suggests that excitotoxic mechanisms might be involved. The present
      study was undertaken to determine whether defects in neurotransmitter receptors
      are involved in the disease, analyzing uniformly sampled specimens from neocortex
      and motorcortex. The binding to benzodiazepine, muscarinic cholinergic, and NMDA
      receptors in ALS brains was compared to that in control brains, using a single
      radioligand concentration of [3H]Ro 15-1788, [3H]QNB and [3H]MK-801. The
      benzodiazepine and the muscarinic cholinergic receptor binding was unaffected in
      any cortical region from the ALS subjects compared to controls. NMDA receptor
      binding labeled by [3H]MK-801 was significantly increased in several neocortical
      regions in the ALS group compared to the control group. Scatchard analysis of
      [3H]MK-801 binding in frontal cortex revealed a single binding site with an
      unaltered maximal binding capacity but an increased binding affinity of the site
      in the ALS group compared to the controls. The generalized alteration in the
      affinity of the binding site for [3H]MK-801 in the ALS cortex may indicate a
      modification of the NMDA receptor due to different sensitivity for endogenous
      modulators or to a different subunit composition of the NMDA receptor in ALS with
      altered functional properties. These findings may reflect a pathophysiological
      phenomenon in ALS.

PMID- 8981310
TI  - Excess glutamate in the cerebrospinal fluid in bacterial meningitis.
AB  - We investigated possible neurotoxic components in the cerebrospinal fluid (CSF)
      of patients with bacterial meningitis. On murine cerebellar neuronal cell
      cultures, CSF exerted a dose-dependent toxic effect, which was attenuated by the
      NMDA receptor antagonist MK-801. Glutamate concentrations in the CSF of patients
      with bacterial meningitis were measured by an enzymatic assay and found to be
      significantly elevated (p < 0.001) as compared to viral meningitis and non
      inflammatory neurological diseases. The concentration of glutamate in the CSF of
      patients with bacterial meningitis varied considerably and correlated with the
      severity of the disease as scored by the Glasgow Coma Scale. Cells in the CSF,
      mainly comprising polymorphonuclear granulocytes, did not release any glutamate
      into the culture medium, whereas blood monocytes produced remarkable amounts.
      These findings implicate an important role of monocytic inflammatory cells in
      bacterial meningitis by the release of glutamate, which may contribute to
      neuronal cell death.

PMID- 8981311
TI  - Justification of hospital days and discharge delays in a non-selected population
      of acute stroke patients.
AB  - Using a published protocol, we evaluated a non-selected population of stroke
      patients to identify unnecessary days of hospitalisation in the Department of
      Neurology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
      This study was undertaken to determine whether physicians can modify the non
      medically justified hospital days. We prospectively studied 118 patients with
      stroke admitted to our Department over a period of 5 months. Each day spent on
      the ward was placed in one of two categories: those due to medical reasons (1,391
      hospital days) and those due to non-medical reason (518 days). Using a previously
      published protocol, 74 parameters were evaluated. Delays in obtaining
      examinations or a specialist's consultation accounted for a small proportion of
      waiting days (1.9% of total hospital days), which was greater in patients who
      were not disabled (0.9% of hospital days) than in patients with total dependence
      (0.2% of hospital days). The delays resulted mainly from awaiting transfer either
      to another department or to a nursing home. The length of stay increased with
      severity of dependence. However, the number of days spent for transfer to a
      nursing home was also relatively high in the non-dependent patient group (42% of
      hospital days). This study demonstrates that neurologists cannot easily influence
      the length of stay in hospital. It also corroborates the need to develop short-
      and long-term chronic care facilities to facilitate the transfer of patients once
      there are no further medical reasons for staying in hospital.

PMID- 8981313
TI  - Brain and spinal cord MR in benign multiple sclerosis: a follow-up study.
AB  - We performed a clinical and magnetic resonance (MR) longitudinal study in 19
      patients with benign multiple sclerosis (MS) to achieve a better definition of
      the nature of disability in MS. Patients with higher lesion volumes on
      conventional T2-weighted images at entry were those with more frequent relapses
      (p = 0.0004) and more new MR lesions (p = 0.003) during the follow up. However,
      1/3 of these new lesions were located periventricularly and about 2/3 were small
      or intermediate in size. Two of the 11 patients (18%) with higher lesion volumes
      at entry developed progressive neurological deficits: in these two patients the
      new lesions seen on conventional T2 images had lower magnetization transfer
      ratios (p = 0.005) than those present in patients who remained clinically stable
      and a marked increase in hypointense lesion volumes on T1-weighted images was
      also found. Spinal cord cross-sectional area at C5 and MTR values for the
      seemingly normal white matter were similar to those found in normal controls.
      This study suggests that patients with benign MS have two different patterns of
      disease evolution, one characterized by very low clinical and MR activities, the
      other in which the lack of disabling symptomatology might be related to factors
      like site, size and nature of lesions. It also indicates that in patients with
      benign MS and high MR lesion loads the risk of developing a secondary progressive
      form of the disease is still present even after many years after onset.

PMID- 8981312
TI  - Copper, iron, and zinc imbalances in severely degenerated brain regions in
      Alzheimer's disease: possible relation to oxidative stress.
AB  - Copper (Cu), iron (Fe), and zinc (Zn) levels in five different brain regions
      (amygdala, hippocampus, inferior parietal lobule, superior and middle temporal
      gyri, and cerebellum) were determined by instrumental neutron activation analysis
      (INAA) in samples from Alzheimer's disease (AD) patients and age-matched control
      subjects. A significant decrease in Cu, and significant increases in Zn and Fe
      were found in AD hippocampus and amygdala, areas showing severe histopathologic
      alterations in AD. None of these elements were significantly imbalanced in the
      cerebellum which is minimally affected in AD.

PMID- 8981314
TI  - A quantitative assessment of the maturation of phasic motor inhibition during REM
      sleep.
AB  - During rapid eye movement (REM) sleep, phasic and further motor inhibition occurs
      during clusters of REMs besides tonic motor inhibition. We describe the age
      related quantitative change of the activity of this REM-related phasic motor
      inhibition. For this purpose, we introduced the phasic inhibition index (PII).
      PII is the rate of simultaneous occurrence of bursts of horizontal REMs and
      phasic mentalis muscle activity during REM sleep. We examined these phasic REM
      sleep parameters in 87 healthy children from premature babies to preadolescents.
      The incidence of bursts of REMs showed no age-related change, while that of the
      phasic mentalis muscle activity increased with age. The simple ratio between the
      incidence of bursts of REMs and that of phasic mentalis muscle activity showed no
      significant age-related change, whereas PII decreased rapidly during infancy and
      reached low constant values thereafter. We concluded that this age-related PII
      decline reflected the maturation of REM-related phasic motor inhibition. This is
      the first quantitative description on the development of human motor inhibition.
      Taken with the neuronal basis underlying REM-related phasic motor inhibition, we
      hypothesize that a PII value is within the normal low range as far as both the
      rostral pontine tegmentum and the brainstem inhibitory pathways are functionally
      intact.

PMID- 8981315
TI  - Immunohistochemical localization of utrophin and other cytoskeletal proteins in
      skin smooth muscle in neuromuscular diseases.
AB  - We investigated the immunohistochemical distribution of cytoskeletal proteins in
      smooth muscles of 15 patients with Duchenne muscular dystrophy (DMD), 8 patients
      with Becker muscular dystrophy (BMD), 28 patients with various neuromuscular
      diseases, and 2 normal controls, performing skin and muscle biopsies. Dystrophin
      immunostaining confirmed absent reaction in the arrector pili muscles of DMD
      patients, faint positive reaction in BMD patients, and strong dystrophin reaction
      in patients with other neuromuscular diseases and normal controls. Immunostaining
      of utrophin was positive with variable intensity in the arrector pili muscles in
      all DMD patients. In BMD patients, utrophin was faintly expressed in the arrector
      pili muscles in 2 cases, and negative in the other 5 patients. In the other cases
      of neuromuscular diseases and in normal controls, immunostaining for utrophin was
      negative in the arrector pili muscles. Staining of the capillary endothelial
      cells and muscular vessel walls was seen in normal controls, as well as in DMD,
      BMD, and other neuromuscular diseases. Vinculin, vimentin and desmin were
      expressed both in arrector pili smooth muscles and in vessel walls of patients
      with dystrophinopathy and other neuromuscular diseases, as well as in normal
      controls. Thus utrophin is normally expressed in the smooth muscle of the vessels
      and its expression does not vary in neuromuscular diseases. On the contrary, in
      the arrector pili smooth muscle utrophin is not expressed in normal controls but
      it is in dystrophinopathies, paralleling the findings in striated muscle, which
      expresses utrophin in a reciprocal manner with respect to dystrophin.

PMID- 8981316
TI  - No association between the neuroleptic malignant syndrome and mutations in the
      RYR1 gene associated malignant hyperthermia.
AB  - The neuroleptic malignant syndrome (NMS) is a drug-induced disease caused by
      neuroleptics, but the pathogenesis of NMS is unknown. Since NMS is similar to
      malignant hyperthermia (MH) in clinical features and treatment, 6 mutations in
      the skeletal muscle ryanodine receptor (RYR1) gene, which were associated with
      MH, were investigated in unrelated NMS patients by single-strand conformation
      polymorphism analysis (SSCP). As a result, MH-susceptible RYR1 mutations were not
      detected in our NMS patients. A single base substitution, C7278T, was detected in
      one patient whose serum CPK level was repetitively elevated, but his other major
      symptoms did not fulfil the clinical criteria for NMS. Our results do not support
      the association between the neuroleptic malignant syndrome and mutations in the
      RYR1 gene associated with malignant hyperthermia.

PMID- 8981317
TI  - 2-Hydroxyglutaric aciduria: a case report on an infant with the D-isomeric form
      with review of the literature.
AB  - We report on an infant with D-2-hydroxyglutaric aciduria, who presented with
      severe seizures and developmental delay. We reviewed the literature for 2
      hydroxyglutaric aciduria and found six other patients with the D-isomer and 24
      patients with the L-isomer. Although the clinical spectrum of this inborn error
      of metabolism is variable, the clinical course of the D-form seems to be more
      severe than this of the L-form.

PMID- 8981319
TI  - Pure progressive clumsiness due to parietal atrophy in a young adult.
AB  - Progressive clumsiness developed in the right hand of a 33-year-old man, became
      bilateral and evolved very slowly for ten years. Another neurological deficit was
      restricted to a slight impairment of superficial sensations. Magnetic resonance
      imaging verified an atrophy of bilateral parietal lobes. The cerebral blood flow
      was markedly decreased in the atrophic area. Pure clumsiness of a very slowly
      progressive course due to parietal atrophy has never been reported in such a
      young adult. This clinical picture may suggest another variety of degenerative
      process.

PMID- 8981318
TI  - Successful treatment of atypical mycobacterial meningitis by fluoroquinolone.
AB  - We report a case of restricted meningeal infection by atypical mycobacteria,
      identified by the polymerase chain reaction, in a non-immunocompromised adult
      successfully treated by multiple antibiotics including fluoroquinolone. New
      quinolones should be considered as a therapeutic option for such mycobacterial
      meningitis.

PMID- 8981320
TI  - Panencephalitic Creutzfeldt-Jakob disease in a Chinese family. Unusual
      presentation with PrP codon 210 mutation and identification by PCR-SSCP.
AB  - A point mutation at codon 210 (GTT to ATT) of the prion protein gene on
      chromosome 20 was found in a 48-year-old CJD-affected woman of a Chinese family.
      This affected woman had an early onset and long-duration form of CJD. Serial
      magnetic resonance image (MRI) analysis of this woman showed severe brain
      atrophy, prominent diffuse white matter degeneration, and subsequent
      mineralization of basal ganglia and thalamus. MR spectroscopy (1H) analysis
      elucidated the absence of peaks of choline, creatine and N-acetylaspartate. Using
      polymerase chain reaction and single-strand conformational polymorphism (PCR
      SSCP) techniques, presymptomatic diagnosis of the second son of this woman showed
      that he has a similar codon mutation of prion gene as his mother.

PMID- 8981321
TI  - Abulia from unilateral capsular genu infarction: report of two cases.
AB  - We report two cases of capsular genu infarction in patients showing pure abulia
      without motor weakness. One case is left-sided infarction, and another is right
      sided. Single photon emission computed tomography (SPECT) examination in both
      disclosed hypoperfusion in the ipsilateral frontal cortex at the infarction. In
      one case, reversion of frontal hypoperfusion was observed later. We considered
      that the frontal hypoperfusion was due to trans-synaptic hypofunction of thalamo
      frontal projections from the deep-seated capsular genu lesion and that it
      resulted in the pure abulia without neurological deficits.

PMID- 8981322
TI  - Valproate induced lupus-like syndrome.

PMID- 8981324
TI  - Sudden "stroke-like' onset of homonymous hemianopsia due to bacterial brain
      abscess.
AB  - A previously healthy 40-year-old man experienced the sudden 'stroke-like' onset
      of homonymous hemianopsia due to a bacterial brain abscess. Clinical features and
      initial computed tomography (CT) suggested a stroke. Subsequent CT and magnetic
      resonance (MR) demonstrated a cerebral abscess, proven at surgery. It is
      extremely rare that a healthy individual without various risk factors, such as
      congenital heart disease, immunologic deficiency, diabetes mellitus, or
      pregnancy, presents with the above symptoms. The exact mechanism of this sudden
      'stroke-like' onset in a patient with a bacterial brain abscess is unknown. One
      possibility is that paroxysmal septic emboli led to abscess formation within or
      near areas of embolic infarction. Another possibility is that a primary cerebral
      infarction was associated with secondary bacteremia. Surgical drainage revealed a
      bacterial (Streptococcus) abscess, but no identifiable source of infection.

PMID- 8981323
TI  - Disseminated cerebral hemorrhages as unusual manifestation of toxoplasmic
      encephalitis in AIDS.
AB  - Hemorrhagic lesions are uncommon in central nervous system (CNS) toxoplasmosis.
      We report here the case of a patient with multiple cerebral hemorrhages as the
      initial manifestation of HIV infection due to CNS toxoplasmosis.

PMID- 8981325
TI  - Domain organizations of modular extracellular matrix proteins and their
      evolution.
AB  - Multidomain proteins which are composed of modular units are a rather recent
      invention of evolution. Domains are defined as autonomously folding regions of a
      protein, and many of them are similar in sequence and structure, indicating
      common ancestry. Their modular nature is emphasized by frequent repetitions in
      identical or in different proteins and by a large number of different
      combinations with other domains. The extracellular matrix is perhaps the largest
      biological system composed of modular mosaic proteins, and its astonishing
      complexity and diversity are based on them. A cluster of minireviews on modular
      proteins is being published in Matrix Biology. These deal with the evolution of
      modular proteins, the three-dimensional structure of domains and the ways in
      which these interact in a multidomain protein. They discuss structure-function
      relationships in calcium binding domains, collagen helices, alpha-helical coiled
      coil domains and C-lectins. The present minireview is focused on some general
      aspects and serves as an introduction to the cluster.

PMID- 8981326
TI  - Exon shuffling and other ways of module exchange.
AB  - Thanks to recent improvements in techniques used for the detection of homologies,
      it is now clear that module exchange played a major role in protein evolution.
      Analysis of the genes of various modular proteins has identified a large number
      of cases where gene assembly was facilitated by intronic recombination--i.e., the
      proteins were formed by exon shuffling. Studies of the principles and mechanistic
      details of exon shuffling, however, revealed that this powerful evolutionary
      mechanism could become significant only after the appearance of spliceosomal
      introns typical of higher eukaryotes. Although exon shuffling is the most
      efficient way of constructing modular proteins, recent studies on the evolution
      of multidomain proteins of prokaryotes emphasize that intronic recombination is
      not an absolute prerequisite of module exchange.

PMID- 8981327
TI  - Structure and function of fibronectin modules.
AB  - Fibronectin is an important component of the extracellular matrix and is involved
      in a diverse range of physiological processes. It is a mosaic protein composed
      almost entirely of three types of module, F1, F2 and F3. Although the structures
      of single F1, F2 and F3 modules have been available for a number of years, in
      many cases the key to understanding the structure-function relationships in
      fibronectin and other proteins containing these modules lies in studies of module
      pairs and larger domains. This review focuses on recent advances in the
      understanding of the structure and function of fibronectin modules.

PMID- 8981328
TI  - Tropoelastin gene expression in optic nerve heads of normal and glaucomatous
      subjects.
AB  - Elastic fibers are a major component of the extracellular matrix in the optic
      nerve head (ONH) and undergo marked morphological changes during primary open
      angle glaucoma (POAG). Previous findings indicated that there is reactivation of
      tropoelastin mRNA synthesis in glaucoma. In this study, we sought to determine
      the alternative splicing pattern of tropoelastin in the human optic nerve head
      and in cultured laminar astrocytes. Furthermore, we compared the alternative
      splicing pattern of normal elastogenesis with that of reactivation of elastin
      synthesis in patients with primary open angle glaucoma. Our results demonstrate
      that exons 23 and 32 of tropoelastin are alternatively spliced in the normal ONH
      as well as in tissue from glaucomatous patients. There are no qualitative
      differences. We also demonstrated that astrocytes from the ONH synthesize
      tropoelastin in vitro. In conclusion, we have demonstrated a tropoelastin
      alternative splicing pattern in the human optic nerve head and laminar
      astrocytes. Abnormalities in elastic fibers in the ONH of patients with POAG are
      not due to an aberrant splice variant of tropoelastin. Astrocytes grown from ONH
      explants may serve as an in vitro model to study extracellular matrix changes in
      glaucoma.

PMID- 8981329
TI  - Developmental regulation of perlecan gene expression in aortic smooth muscle
      cells.
AB  - Heparan sulfate proteoglycans (HSPGs) are believed to act as potent endogenous
      regulators of vascular smooth muscle cell (SMC) replication, migration, gene
      expression and differentiation. Here we describe the pattern of expression of
      perlecan, the predominant basement membrane HSPG, during aortic development in
      the rat. Expression of perlecan mRNA and protein in the aortic SMC was first
      significantly observed at day e19 (day 19 of embryonic development), a time which
      marks a dramatic switch in SMC replication rate and growth phenotype. Expression
      of perlecan message and protein was high throughout fetal and early neonatal
      life, and it remained readily detectable in the adult aorta. Using a double
      labeling technique (in situ hybridization for perlecan message coupled with
      bromodeoxyuridine immunohistochemistry), we determined the relationship between
      DNA synthesis and perlecan mRNA expression in individual SMC at days e17-e21; we
      found that perlecan gene expression was largely limited to non-replicating cells.
      Consistent with the in vivo data, perlecan mRNA was undetectable in cultured e17
      SMC by Northern or RT-PCR analysis, while in cultured adult SMC, perlecan mRNA
      was significantly higher in non-replicating (serum-starved) cultures compared to
      replicating cultures. Treatment of growth-arrested adult SMC cultures with
      heparin caused a further accumulation in perlecan mRNA levels. The data suggest
      that the expression of perlecan by vascular SMC is regulated by apparent
      developmental age as well as by cellular growth state. The developmentally times
      expression of perlecan in the aortic wall may contribute to the establishment
      and/or maintenance of vascular SMC differentiation and quiescence.

PMID- 8981330
TI  - Characterization of the interactions of type XII collagen with two small
      proteoglycans from fetal bovine tendon, decorin and fibromodulin.
AB  - In addition to the major collagens, such as type I or type II, connective tissues
      contain a number of less abundant collagens and proteoglycans, whose association
      contributes to the different properties of the tissues. Type XII and type XIV
      collagens have been described in soft connective tissues, and type XIV collagen
      has been shown to interact specifically with decorin through its
      glycosaminoglycan chain (Font et al., J. Biol. Chem. 268, 25015-25018, 1993).
      Interactions between these collagens and the small proteoglycans have been
      characterized further by studying the binding of type XII collagen to decorin by
      solid phase assays. Our results show a saturable binding of the proteoglycan
      through its glycosaminoglycan chain to type XII collagen, which does not seem to
      involve the large non-collagenous NC3 domain of the molecule. This interaction is
      strongly inhibited by heparin. Furthermore, we report that another small
      proteoglycan, fibromodulin, isolated from tendon under non-denaturing conditions,
      is able to bind to type XII collagen. This interaction has been characterized
      and, unlike that observed with decorin, type XII collagen-fibromodulin
      interaction seems to take place with the core protein of the proteoglycan. In
      addition, we report that type XII-type I collagen interactions are not
      necessarily mediated by decorin as previously suggested.

PMID- 8981331
TI  - Structural and cell-adhesive properties of three recombinant fragments derived
      from perlecan domain III.
AB  - Domain III of the basement membrane proteoglycan perlecan was produced as three
      overlapping fragments in stably transfected mammalian cell clones. These
      recombinant fragments (43-48 kDa) were obtained in purified form and showed
      complete immunological cross-reactivity with perlecan, indicating their native
      structure. Rotary shadowing electron microscopy of each fragment demonstrated a
      small globular structure connected to a short rod. These data were interpreted to
      indicate that domain III has an elongated shape of 30 nm in length and consists
      of alternating globular domains (L4 modules) and short connecting segments
      attributed to tandem arrays of LE (laminin-type of EGF-like) modules which form
      rod-like segments in laminins. Sequence analyses of pepsin fragments were
      consistent with the disulfide-bonding patterns known for these modules from
      studies with laminin fragments, but two additional disulfide loops were also
      identified. Several cell lines which attached to mouse perlecan and/or human
      fibronectin failed to adhere to the domain III fragments, despite the fact that
      one of them contained an RGD (Arg-Gly-Asp) site in the L4 module. Furthermore, no
      significant binding was observed in solid phase binding assays with alpha 5 beta
      1 and alpha v beta 3 integrins underscoring the low activity or accessibility of
      the RGD site.

PMID- 8981332
TI  - The mouse col11a2 gene. Some transcripts from the adjacent rxr-beta gene extend
      into the col11a2 gene.
AB  - Type XI collagen is present in small amounts in cartilage, together with small
      amounts of type IX and type V collagens and large amounts of type II collagen.
      Here, primers based on the nucleotide sequences of partial human cDNAs and mouse
      genomic DNAs that were analyzed by other investigators were used to isolate a
      cDNA for the mouse col11a2 gene. Cosmid clones for the mouse col11a2 gene were
      isolated, and 12.4 kb of the nucleotide sequences were defined. Analysis of the
      genomic sequences identified three exons in the mouse gene that were recently
      shown to undergo alternative splicing (Tsumaki and Kimura, J. Biol. Chem. 270,
      2372-2378, 1995; Zhidkova et al., J. Biol. Chem. 270, 94886-9493, 1995). In
      addition, analysis of the cosmid clones revealed that the 5' end of the mouse
      col11a2 gene was located head-to-tail with the mouse retinoic X receptor beta
      gene. RT-PCR assays demonstrated that some transcripts from the retinoic X
      receptor beta gene extend into the col11a2 gene. Therefore, there may be
      coordinate expression of the two genes.

PMID- 8981333
TI  - Comparison of two estradiol transdermal systems (Oesclim 50 and Estraderm TTS
      50). I. Tolerability, adhesion and efficacy.
AB  - OBJECTIVES: The objectives were to compare the tolerability, adhesion and
      efficacy of a new matrix-type estradiol transdermal system, Oesclim 50, with
      those of Estraderm TTS 50, a reservoir-type system. METHODS: This was an open,
      randomised, parallel-group, multi-centre clinical trial, performed in six
      European countries. A total of 143 healthy menopausal women were allocated to
      treatment with Oesclim 50 and 140 to Estraderm TTS 50. The transdermal systems
      were applied twice weekly for 24 days out of each 28-day cycle, over a period of
      four cycles. Oral progestogen treatment was taken by non-hysterectomised patients
      for the last 12 days of estrogen therapy in each cycle. RESULTS: The local skin
      tolerability of the Oesclim 50 transdermal system was significantly better than
      that of Estraderm TTS 50. In the Oesclim 50 group, 4.2% of applications caused a
      reaction, compared with 9.5% in the Estraderm TTS 50 group (P < 0.001). Safety
      assessments showed both treatments to be well tolerated. Seven patients in the
      Oesclim 50 group, and 12 in the Estraderm TTS 50 group, discontinued due to
      adverse events. Of these discontinuations, one (0.7% of patients) in the Oesclim
      50 group and seven (5.1% of patients) in the Estraderm TTS 50 group were due to
      application site reactions (P < 0.05). There was no statistically significant
      difference between the two groups in the percentage of patients with signs of
      hyperestrogenism (29 patients (20.3%) in the Oesclim group and 28 patients
      (20.0%) in the Estraderm TTS 50 group). Adhesion was significantly better for the
      Oesclim 50 transdermal system, with 6.0% of Oesclim 50 applications becoming
      detached compared with 11.3% of Estraderm TTS 50 applications (P < 0.001). The
      greater adhesion of Oesclim 50 was particularly apparent when the systems were
      exposed to water, with three times fewer Oesclim 50 systems becoming detached
      during a shower or bath (P < 0.001 in each case). Both treatments produced
      significant and comparable improvements in vasomotor symptoms, other menopausal
      symptoms and gynaecological assessments. A near-maximal effect on vasomotor
      symptoms was observed after approximately 1 month of treatment, and was
      maintained for the entire treatment period. CONCLUSION: Overall, Oesclim 50
      provided statistically significantly better local skin tolerability and adhesion
      than Estraderm TTS 50, together with comparable efficacy and safety.

PMID- 8981334
TI  - Comparison of two estradiol transdermal systems (Oesclim 50 and Estraderm TTS
      50). II. Local skin tolerability.
AB  - OBJECTIVES: The objectives were to compare the local skin tolerability of a
      matrix-type estradiol transdermal system, Oesclim 50, with that of the reservoir
      type system, Estraderm TTS 50. METHODS: Two randomised studies were performed. In
      the first study, the modified Draize-Shelanski-Jordan method of sensitization was
      used in an open, parallel-group trial to compare the cutaneous tolerability of
      repeated applications of Oesclim 50 with that of Estraderm TTS 50 in 24 healthy
      postmenopausal women. The second study was an open, randomised, parallel-group,
      multi-centre clinical trial involving 283 healthy menopausal women. A total of
      143 women were allocated to treatment with Oesclim 50 and 140 to Estraderm TTS
      50. The treatment duration was four months. RESULTS: The first study showed that
      the treatments, Oesclim 50 and Estraderm TTS 50, had no sensitizing potential and
      did not induce allergic reactions. In the second study, 4.2% of applications in
      the Oesclim group provoked reactions compared with 9.5% in the Estraderm group (P
      < 0.001). Thirty-seven patients (25.9%) treated with Oesclim and 55 patients
      (39.9%) receiving Estraderm experienced one or more reactions (P < 0.05). Redness
      and itching were the most frequent types of application site reaction in both
      treatment groups. The durations of the reactions were significantly shorter in
      the Oesclim group (P < 0.01), with a higher percentage of durations of less than
      1 h and a lower percentage of durations of over 48 h than in the Estraderm TTS 50
      group. None of the reactions in the Oesclim group led to premature removal of the
      patch, compared with 11 (3.4%) in the Estraderm group (P < 0.05). The number of
      patients who discontinued treatment due to application site reactions was one
      (0.7%) in the Oesclim group and seven (5.1%) in the Estraderm group (P < 0.05).
      Efficacy and general safety were comparable in the two treatment groups.
      CONCLUSIONS: In the first study, neither Oesclim nor Estraderm induced allergic
      reactions. In the second study, the local skin tolerability of Oesclim was
      significantly better than that of Estraderm, in terms of the number, duration and
      severity of the application site reactions.

PMID- 8981335
TI  - Diagnostic accuracy of hysteroscopy in endometrial hyperplasia.
AB  - OBJECTIVES: To determine the diagnostic accuracy of hysteroscopy in the diagnosis
      of endometrial hyperplasia in women with abnormal uterine bleeding. METHODS: From
      1993 through 1995, 980 women referred to our institution for abnormal uterine
      bleeding underwent diagnostic hysteroscopy with eye direct biopsy of the
      endometrium in case of macroscopic abnormalities. Hysteroscopic features were
      compared with pathologic findings in order to detect the reliability of the
      endoscopic procedure. Statistical analysis was performed with the McNemar test.
      RESULTS: Positive predictive value of hysteroscopy in the diagnosis of
      endometrial hyperplasia accounted for 63%. In fact hysteroscopic diagnosis of
      endometrial hyperplasia was confirmed at pathologic examination in 81 out of 128
      patients. Sensitivity and specificity of the endoscopic procedure accounted for
      98% and 95%, respectively. Negative predictive value accounted for 99%, as only
      two cases of atypical hyperplasia were missed at hysteroscopy. Positive
      predictive value was higher in postmenopausal patients compared to women in the
      fertile age (72 vs. 58%). CONCLUSIONS: Overall, results appear encouraging, since
      no case of endometrial hyperplasia was missed by hysteroscopy. The high
      diagnostic accuracy, associated with a minimal trauma, renders hysteroscopy the
      ideal procedure for both diagnosis and follow-up of conservative management of
      endometrial hyperplasia.

PMID- 8981337
TI  - Prevalence of hormone replacement therapy and user's characteristics: a community
      survey in Japan.
AB  - OBJECTIVES: It is quite recently that much interest has been paid to the benefits
      of hormone replacement therapy (HRT) in Japan. We conducted a community survey in
      Japan in 1992 to examine the prevalence of HRT use and factors related to HRT
      use. METHODS: A total of 8791 female residents aged 45-64 years old in a city of
      the Gifu Prefecture, Japan, responded to the questionnaire including medical and
      reproductive histories, lifetime occupational history, diet, exercise, smoking
      and drinking habits, and use of vitamin supplements or medications. The response
      rate was 94.2%. RESULTS: Overall, 2.5% of women reported current use of HRT and
      6.3% had used HRT previously. The highest prevalence of current use was found
      among postmenopausal women with surgical menopause (4.8%). Current users were
      more likely to have participated in cancer screenings, and to have used vitamin
      supplements or calcium during the past year. CONCLUSIONS: HRT use rate was 2.5%
      among female residents aged 45-64 years old in a Japanese community in 1992.
      Current users may have more regard for their health status.

PMID- 8981336
TI  - Hormone replacement therapy and previous use of oral contraceptives among Swedish
      women.
AB  - OBJECTIVES: To assess the current and previous use of hormone replacement therapy
      (HRT) and alternative remedies in a postmenopausal population and to relate HRT
      use to previous use of oral contraceptives. MATERIAL AND METHODS: All 1323 women
      living in Linkoping of 55 or 56 years old during 1995 were sent a questionnaire
      asking for data with relation to health and climacteric symptoms as well as to
      previous and current use of HRT, oral contraceptives and alternative remedies.
      RESULTS: Current use of HRT was more common among women who previously used oral
      contraceptives (41.3%) than among women who had never used oral contraceptives
      (23.1%). HRT users were also more often physically active, had undergone
      hysterectomy and had lighter occupation than non-users. Of all women 35% were
      current users of HRT, half of them for at least 2 years, whereas only 5% had
      tried HRT and abandoned therapy. Alternative remedies were used by 5% of the
      women as therapy for climacteric complaints, and about four times as many women
      had tried such therapy but abandoned it. The only characteristic about use of
      alternative medicines was that they were used less often by women who had been
      hysterectomized. No women treated for breast cancer used HRT and only few of them
      used alternative remedies. CONCLUSIONS: The prevalence of HRT use, as well as
      compliance, was high. Previous use of oral contraceptives probably affected the
      attitude towards using HRT.

PMID- 8981338
TI  - Changes of the basement membrane and type IV collagen in human skin during aging.
AB  - OBJECTIVES: To determine the relationship between skin collagen IV and basement
      membrane changes during aging, a total of 35 women who had been admitted for
      surgery, were studied. METHODS: Subjects were arranged into six age-groups (from
      35 to 60 years). Skin biopsies were performed in all patients and the samples
      were taken from a site 6 cm above the pubic symphysis. The collagen IV content
      and the epithelial basement membrane were analyzed by using immunohistochemical,
      transmission electron microscopy and computer-assisted image analysis methods.
      The skin collagen IV content was measured by an image analysis program and
      expressed in arbitrary units of integrate optical density, and, the basement
      membrane thickness was expressed in nanometers. RESULTS: Type IV collagen content
      decreased with age after 35 years (r = -0.9561). The epithelial basement membrane
      thickness increased significantly with age (r = 0.98192; P < 0.01) and there is
      an inverse correlation between these two parameters (r = -0.990502). CONCLUSIONS:
      Although type IV collagen is a basement membrane component and declines with
      aging, the total thickness of this membrane increases, which suggests a reduction
      in tissue turnover.

PMID- 8981339
TI  - Effect of estrogen replacement therapy on natural killer cell activity in
      postmenopausal women.
AB  - OBJECTIVE: To evaluate the impact of menopause and estradiol substitution on
      natural killer cell activity. METHODS: Natural killer cell activity and antibody
      dependent cellular cytotoxicity were measured in peripheral blood of 53
      postmenopausal and 20 premenopausal women in an interval of 3 weeks.
      Postmenopausal patients were randomly assigned to receive either estradiol
      valerate (2 mg daily) orally (n = 18), estradiol (50 micrograms/24 h)
      transcutaneously (n = 18) or no substitution (n = 17), and the testing was
      repeated 3 weeks later. RESULTS: Natural killer cell activity but not antibody
      dependent cellular cytotoxicity was significantly (P < 0.01) higher in
      unsubstituted postmenopausal compared to premenopausal subjects. Natural killer
      cell activity decreased both in orally and transcutaneously estradiol-treated
      patients (mean [S.D.] before vs. after 3 weeks; oral: 60.8 [9.2]% vs. 52.8 [8.2]%
      P < 0.01; transcutaneous: 61.5 [10.6]% vs. 54.3 [9.1]% P < 0.01; no substitution:
      60.6 [10.6]% vs. 59.3 [8.9]% P > 0.1), whereas antibody-dependent cellular
      cytotoxicity showed no changes. The addition of 0.1 to 10 ng/ml estradiol to
      peripheral blood mononuclear cells of untreated postmenopausal women in vitro had
      no influence upon natural killer cell activity. CONCLUSION: Postmenopausal women
      receiving no estrogen replacement exhibited an increased natural killer cell
      activity which decreased during estrogen substitution.

PMID- 8981340
TI  - Lack of microbial proliferation and phototoxic potential of a new matrix patch
      for estradiol delivery.
AB  - OBJECTIVES: To examine the potential of a new matrix system developed for
      estradiol delivery to cause microbial proliferation under the occluded site or to
      cause acute phototoxicity reactions. METHODS: Twenty healthy post-menopausal
      women participated in a microbial proliferation study and 11 in a phototoxicity
      study. Both studies were single centre, single blind and placebo controlled.
      Microbial proliferation was assessed by quantitative counts of the total aerobic
      bacterial population and of eight individual species before patch application and
      after removal following a 4 day application period on the abdomen. Acute
      phototoxicity potential was assessed following an 8 h application period on the
      abdomen by irradiating the application site after patch removal with ultra violet
      A radiation and visible light and evaluating the sites for up to 48 h post
      irradiation. Non-irradiated active and placebo patches on the other side of the
      abdomen served as controls. RESULTS: Total aerobic bacterial populations both
      before and after the matrix patch application period were low as expected for dry
      skin. Separate counts of microbial species were also low and did not change in
      any meaningful or consistent manner after patch application. In the phototoxicity
      study, mild erythema was observed in some patients at 0, 0.5 and 24 h post patch
      removal with no differences between irradiated and non-irradiated sites.
      CONCLUSIONS: These two studies demonstrate that a new matrix patch developed for
      estradiol delivery does not promote microbial proliferation under the occluded
      patch site or cause acute phototoxicity following removal.

PMID- 8981341
TI  - Role of microbial proteases in pathogenesis.

PMID- 8981342
TI  - Rotavirus vaccines: a perspective.

PMID- 8981343
TI  - Acid-fastness of Nocardia asteroides GUH-2 cultured in brain heart infusion broth
      supplemented with paraffin.
AB  - Nocardia asteroides GUH-2 was not acid-fast when grown in brain heart infusion
      (BHI) broth. When grown in BHI broth supplemented with paraffin, many filamentous
      cells showed acid-fastness after treatment with 1% acid-alcohol as the
      decolorizing agent. When treated with 3% acid-alcohol, filamentous cells were not
      acid-fast. In addition to the acid-fast filamentous cells of nocardiae, unknown
      acid-fast spherical bodies were observed in the paraffin-supplemented BHI broth
      cultures.

PMID- 8981344
TI  - Characterization of Actinobacillus actinomycetemcomitans hemolysin.
AB  - Twenty out of 33 Actinobacillus actinomycetemcomitans strains formed hemolytic
      colonies on horse blood agar plates under anaerobic conditions. The hemolytic
      activity found in A. actinomycetemcomitans strain 137HE was examined. This
      activity was detected in the late exponential to early stationary phases of
      growth. Human erythrocytes were the most susceptible, followed by rabbit, sheep,
      horse and swine red blood cells. The majority of activity was detected in the
      cell-associated vesicle fraction. Zwitterionic detergent 3-[(3-cholamidopropyl)
      dimethyl-ammonio]-1-propanesulfonate (CHAPS) extract from whole cells was
      semipurified by ammonium sulfate precipitation, preparative isoelectric focusing
      (IEF) and gel-filtration chromatography to yield a major band on sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with a molecular mass of 12
      kDa. Heating at 80 C for 30 min and treatment with proteinase K or trypsin
      resulted in complete disappearance of the hemolytic activity. Sulphydryl reagents
      enhanced activity and small amounts of cholesterol inhibited it. In summary, we
      demonstrated the presence of hemolysin in A. actinomycetemcomitans, and examined
      and characterized it.

PMID- 8981345
TI  - Sequence and product analyses of the four genes downstream from the fimbrilin
      gene (fimA) of the oral anaerobe Porphyromonas gingivalis.
AB  - The downstream DNA region of the fimbrilin gene (fimA), which encodes the major
      subunit protein of Porphyromonas gingivalis fimbriae, was fully sequenced. Gene
      products, expressed from this region in Escherichia coli, were purified by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, and their partial amino acid
      sequences were determined to verify open reading frames (ORFs) found in the
      region by DNA sequencing. Four ORFs, designated ORF1, ORF2, ORF3 and ORF4, were
      found in the 5.8-kb PstI fragment downstream from fimA, which was previously
      cloned and partially characterized by Yoshimura, Takahashi, Hibi, Takasawa, Kato,
      and Dickinson (Infect. Immun. 61: 5181-5189, 1993). The direction of
      transcription of all the ORFs was the same as that of fimA. The 50 and 80 kDa
      encoded proteins, ORF2 and ORF3, respectively, have been reported to be minor
      components associated with fimbriae. The 15 and 19 kDa proteins, ORF1 and ORF4,
      respectively, have been expressed in E. coli but not identified in P. gingivalis.
      However, all the gene products of the ORFs, expressed in E. coli, appeared to
      contain intact signal peptides based on their N-terminal amino acid sequences.

PMID- 8981346
TI  - An N-[(R)-(-)-2-hydroxypropionyl]-alpha-L-perosamine homopolymer constitutes the
      O polysaccharide chain of the lipopolysaccharide from Vibrio cholerae O144 which
      has antigenic factor(s) in common with V. cholerae O76.
AB  - Chemical and serological studies were performed with the lipopolysaccharide (LPS)
      from Vibrio cholerae O144 (O144). The LPS of O144 contained D-glucose, D
      galactose, L-glycero-D-manno-heptose, D-fructose, D-quinovosamine (2-amino-2,6
      dideoxy-D-gluco-pyranose) and L-perosamine (4-amino-4,6-dideoxy-L-manno
      pyranose). The perosamine, a major component sugar of the LPS from O144, was in
      an L-configuration, as is also the case in the LPS from V. cholerae O76 (O76), in
      contrast to the D-configuration of the perosamine in the LPS of V. cholerae O1. A
      structural analysis revealed that the O polysaccharide chain of the LPS from O144
      is an alpha(1-->2)-linked homopolymer of (R)-(-)-2-hydroxypropionyl-L-perosamine.
      The serological cross-reactivity between O144 and O76 was clearly revealed by
      cross-agglutination and cross-agglutinin absorption tests with whole cells, as
      well as by passive hemolysis tests with sheep red-blood cells that had been
      sensitized with the LPS from O144 and O76. In contrast, in passive hemolysis
      tests, the LPS of O144 did not cross-react serologically with the LPSs from other
      strains such as V. cholerae O1 (Ogawa and Inaba), V. cholerae O140, Vibrio bio
      serogroup 1875 (Original and Variant) and Yersinia enterocolitica O9. The LPSs
      from these strains consist of O polysaccharide chains composed of alpha(1-->2)
      linked homopolymers of D-perosamine with various N-acyl groups, and they share
      the Inaba antigen factor C of V. cholerae O1 in common. The results obtained in
      this study demonstrate that the absolute configuration of the perosamine residue
      in homopolymers plays a very important role in the expression of the serological
      specificity of the Inaba antigen factor C of V. cholerae O1.

PMID- 8981347
TI  - Virulence in mice of Orientia tsutsugamushi isolated from patients in a new
      endemic area in Japan.
AB  - Four strains of Orientia tsutsugamushi (KN-1, KN-2, KN-3 and GJ-1) isolated from
      patients in an area of Gifu Prefecture, Japan, in which tsutsugamushi disease is
      newly endemic, were examined for their virulence in mice. Among these, KN-1
      (identified as Kawasaki type), GJ-1 (identified as Kuroki type) and KN-2 strains
      were found to be non-lethal for BALB/c mice as well as CH3/HeJ mice, even with
      high doses (10(6) x being the 50% mouse infectious dose). On the other hand, the
      KN-3 strain was found to be sufficiently virulent to kill BALB/c mice. Among the
      prototype strains (Gilliam, Karp and Kato), the Karp and Kato strains exhibited
      high virulence to mice, while the Gilliam strain killed only a susceptible strain
      of mouse. BALB/c mice infected with KN-1 and KN-2 strains showed significant
      splenomegaly and moderate ascites accumulation in the first week of infection,
      while these symptoms became prominent during the second week of infection using
      KN-3, Karp and Kato strains. After infection with the GJ-1 strain, these symptoms
      were not observed. Antibody responses induced by infections with highly virulent
      strains were lower than that with low or intermediate virulent strains.

PMID- 8981348
TI  - Electron microscopy of the major outer membrane protein of Campylobacter jejuni.
AB  - The surfaces of the disrupted-cell surfaces of the Campylobacter jejuni strains
      FUM158432 and M1 were examined using the negative-staining technique and electron
      microscopy. The surfaces of the whole cells and the outer membranes were covered
      with small dark dots which, in some areas, were arranged in hexagonal patterns.
      The hexagonal arrangement was more clearly seen in extracted outer membrane. The
      size of each structure was measured based on a center-to-center distance with the
      adjacent structure, and was determined to be 9.9 +/- 0.9 nm. A profile of the
      proteins in the outer membrane by SDS-PAGE, performed in 0.1% SDS and at 100 C,
      showed 42 kDa proteins to comprise the major outer membrane protein of this
      bacterium. Digestion of the outer membrane materials with proteinase reduced this
      protein band in the SDS-PAGE, and the amount of dark dots on the electron
      micrograph indicated the structure to be the major outer membrane protein (porin)
      of this bacterium. The power spectrogram of a computer-assisted Fourier
      transformation of the hexagonally arranged porin proteins suggests that the porin
      has a trimeric structure rather than a monomeric one.

PMID- 8981349
TI  - Seroepidemiology of feline chlamydiosis by microimmunofluorescence assay with
      multiple strains as antigens.
AB  - The prevalence of anti-chlamydia antibodies was examined in 232 cat sera
      collected in 1985 and from 1993 to 1995 from laboratories and veterinary
      hospitals located in 11 prefectures of Japan. The antibodies were determined by
      an indirect microimmunofluorescence test using six strains of feline Chlamydia:
      one strain each of avian- and guinea pig-derived C. psittaci and one strain each
      of C.pecorum, C.pneumoniae and C.trachomatis. Positive rates of IgG antibodies to
      chlamydiae were 34.4% in 1985 and 16.5-21.4% from 1993 to 1995. Positive rates of
      IgM antibodies to chlamydiae were 8.2% in 1985 and 6.6-14.3% from 1993 to 1995.
      Variations in antibody reactivity to the different feline strains were observed.
      The results suggest the wide prevalence of chlamydial infection in cats in Japan,
      and antigenic diversity in the feline strains of C.psittaci.

PMID- 8981350
TI  - Further search for small molecular inactivants capable of eliciting respiratory
      mucosal immunogenicity by modifying Sendai virus core RNA.
AB  - Five groups of 32 chemicals were examined regarding their immunological functions
      as modifier inactivants to make inactivated Sendai nasal vaccine using a contact
      exposure experiment, direct immunofluorescent method, and serum HI titer. (1)
      Five of the nine reactive groups of reactive dyes (2-chloropyridine, 2, 4, 6
      trichloropyrimidine, vinylsulfonic acid, epichlorohydrin and beta
      chloroethylamine) induced complete or almost complete defense in the entire
      respiratory tract, and the four other vaccines brought about slight infection in
      the respiratory tracts. There was no marked rise in serum HI titers post
      exposure, despite uneven development. (2) Of the four sizable substituted AS
      naphthol vaccines, naphthol AS-IRG and AS-G vaccines elicited nearly complete
      defense, but the two other vaccines, inactivated with more elongated molecules,
      invited rare and successive infections. The three immune groups produced
      invariably high serum HI titers. (3) Of the six naphthalene derivative vaccines,
      two (3-hydroxy-2-naphthoic acid methylester and 2-naphthol-6-sulfonic acid)
      induced complete or almost complete protection. But two vaccines brought about
      less protection, and the remaining two vaccines caused heavy infections. (4) Of
      the six benzene derivative vaccines, both m-nitrobenzenesulfonic acid and isatoic
      anhydride induced complete protection. Three vaccines permitted slight infections
      but 2, 4, 6-trinitrobenzenesulfonic acid vaccine caused severe infection. (5) Of
      the seven food dye vaccines, only orange I induced complete or nearly complete
      defense, while the other dye vaccines were inferior. In effect, twelve
      inactivated Sendai nasal vaccines modified the ribose and/or phosphate groups of
      the virus core RNA through five groups of small-sized molecules with specially
      fixed side chains, and elicited complete or almost complete respiratory mucosal
      defense. The viral stabilization requiring the least alteration of the
      configuration will be involved in the chemical modification.

PMID- 8981351
TI  - Nosocomial diarrhoea in the elderly due to enterotoxigenic Clostridium
      perfringens.
AB  - To diagnose sporadic diarrhoea due to Clostridium perfringens infection, faecal
      specimens from elderly patients were examined directly for C.perfringens
      enterotoxin using reverse passive latex agglutination assay, and then cultured
      for this organism. C.perfringens isolates from those samples were grouped by
      slide agglutination and by pulsed-field gel electrophoresis (PFGE). Fifty of the
      60 isolates agglutinated with newly raised antiserum WX2 and 38 shared the same
      genomic PFGE pattern. Characteristics of the epidemics and experimental data
      suggest that the diarrhoea was caused by a nosocomial spread of C.perfringens,
      and not by a food-borne outbreak.

PMID- 8981352
TI  - Detection and identification of Yersinia pestis by polymerase chain reaction
      (PCR) using multiplex primers.
AB  - A PCR method for detection of Yersinia pestis-virulence determinants by the use
      of multiplex primers was developed. Four pairs of oligonucleotide primers were
      designed from each gene of three kinds of virulent plasmids and a chromosomal
      DNA; 60-Md plasmid-located gene (caf1)encoding Y.pestis-specific capsular antigen
      fraction 1, a Y.pestis-specific region of a yopM gene encoded on 42-Md virulent
      plasmid, a plasminogen activator gene (pla) encoded on Y.pestis-specific 7-Md
      plasmid and an invasin protein gene (inv) encoded on chromosomal DNA. This
      multiplex-primer system was specific for the detection of Y.pestis among
      pathogenic Yersinia species and other enterobacteriaceae having antigens common
      to Y.pestis. Since this method is simple and safe, it will be useful to identify
      and confirm Y.pestis in cases of emergency and for the surveillance of epidemics.

PMID- 8981353
TI  - Investigation of IFN type-I receptor and IFN regulatory factor expression
      relating to induction of 2', 5'-oligoadenylate synthetase in cells persistently
      infected with the mumps virus.
AB  - Poor induction of interferon-induced 2', 5'-oligoadenylate synthetase (2-5AS)
      activity has been demonstrated in cells persistently infected with the mumps
      virus or human T-lymphotropic virus type-I (HTLV-I). The suppression of 2-5AS
      induction is the result of the repression of 2-5AS gene expression at the
      transcription level. In a general way, after the binding of interferon-alpha (IFN
      alpha) to cell surface-specific receptors, expression of 2-5AS gene is thought to
      be regulated by some transacting factors, IFN-regulatory factors (IRF-1 and IRF
      2) and the IFN-stimulated gene factor (ISGF-3, a complex consisting of STAT-1
      alpha, STAT-2 and p48). To clarify the cause of the suppression mechanism(s),
      fluctuation in the number of IFN receptors and the levels of mRNAs in both IRF-1
      and IRF-2 were examined in cells persistently infected with the mumps virus (FLMT
      and KBMT). There were few differences in the number of IFN receptors and the
      level of IRF-2 mRNA between persistently infected cells and uninfected control
      cells. After the treatment of cells with IFN, a slight reduction of IRF-1 mRNA
      was found in persistently infected cells as compared with that of the uninfected
      control cells.

PMID- 8981355
TI  - Pentoxifylline pretreatment enhances the oxidative burst activity of human
      peripheral blood mononuclear cells.
AB  - The effect of pentoxifylline pretreatment on the lucigenin-augmented
      chemiluminescence and dismutase-inhibitable superoxide production of human
      neutrophils and mononuclear cells (MNCs) was studied. Pentoxifylline at 20-2,000
      micrograms/ml enhanced the lucigenin-augmented chemiluminescence (118-165% of the
      control, P < 0.01) of phorbol myristate acetate (PMA)-stimulated MNC.
      Pentoxifylline at 20-2,000 micrograms/ml increased the MNC superoxide production,
      i.e., 142-171% of the control (P < 0.05) using PMA stimulation and 145-159% of
      the control (P < 0.01) using opsonized zymosan stimulation. In contrast,
      pentoxifylline (up to 2,000 micrograms/ml) did not influence the lucigenin
      augmented chemiluminescence and superoxide production of human neutrophils,
      stimulated by either PMA or opsonized zymosan. These results suggest that
      pentoxifylline is an immunomodulator and may have potential usefulness in the
      enhancement of immune defenses in compromised hosts.

PMID- 8981354
TI  - Adhesiveness for extracellular matrices and lysosomal enzyme release from normal
      and beta 2 integrin-deficient bovine neutrophils.
AB  - The adhesiveness of control and CD18-deficient bovine neutrophils on culture
      plates precoated with collagen I, collagen IV, fibronectin and laminin was
      measured to evaluate the possible factors for adherence to extracellular
      matrices. The release of N-acetyl-beta-D-glucosaminidase (NAGase) from control
      and CD18-deficient neutrophils stimulated with complement receptor type 3 (CR3)
      or Fc receptor dependent stimuli was also evaluated. The adhesive activities of
      CD18-deficient neutrophils to collagen I, collagen IV and fibronectin were
      significantly diminished (P < 0.05); however, similar adhesion to laminin was
      observed in CD18-deficient neutrophils and control neutrophils. The adhesive
      activity of control neutrophils on uncoated plates increased 2.5 times (P < 0.05)
      with the presence of PMA. The mean activities for NAGase release from CD18
      deficient neutrophils stimulated with opsonized zymosan and aggregated bovine
      immunoglobulin G (Agg-IgG) were 46.7 and 82.7% that of the control neutrophils,
      respectively. The Agg-IgG-induced NAGase release from control and CD18-deficient
      neutrophils was eliminated by H7, a protein kinase C inhibitor. These results
      support that an association between CR3 and Fc receptors on neutrophils appears
      to play an essential role in neutrophil functions.

PMID- 8981356
TI  - Symposium on colony-stimulating factor in development and disease. Ames, Iowa,
      September 1995. Proceedings.

PMID- 8981357
TI  - Biology and action of colony--stimulating factor-1.
AB  - Colony-stimulating factor-1 (CSF-1), also known as macrophage colony-stimulating
      factor, controls the survival, proliferation, and differentiation of mononuclear
      phagocytes and regulates cells of the females reproductive tract. It appears to
      play an autocrine and/or paracrine role in cancers of the ovary, endometrium,
      breast, and myeloid and lymphoid tissues. Through alternative mRNA splicing and
      differential post-translational proteolytic processing, CSF-1 can either be
      secreted into the circulation as a glycoprotein or chondroitin sulfate-containing
      proteoglycan or be expressed as a membrane-spanning glycoprotein on the surface
      of CSF-1-producing cells. Studies with the op/op mouse, which possesses an
      inactivating mutation in the CSF-1 gene, have established the central role of CSF
      1 in directly regulating osteoclastogenesis and macrophage production. CSF-1
      appears to preferentially regulate the development of macrophages found in
      tissues undergoing active morphogenesis and/or tissue remodeling. These CSF-1
      dependent macrophages may, via putative trophic and/or scavenger functions,
      regulate characteristics such as dermal thickness, male fertility, and neural
      processing. Apart from its expression on mononuclear phagocytes and their
      precursors, CSF-1 receptor (CSF-1R) expression on certain nonmononuclear
      phagocytic cells in the female reproductive tract and studies in the op/op mouse
      indicate that CSF-1 plays important roles in female reproduction. Restoration of
      circulating CSF-1 to op/op mice has preliminarily defined target cell populations
      that are regulated either humorally or locally by the synthesis of cell-surface
      CSF-1 or by sequestration of the CSF-1 proteoglycan. The CSF-1R is a tyrosine
      kinase encoded by the c-fms proto-oncogene product. Studies by several groups
      have used cells expressing either the murine or human CSF-1R in fibroblasts to
      pinpoint the requirement of kinase activity and the importance of various
      receptor tyrosine phosphorylation sites for signaling pathways stimulated by CSF
      1. To investigate post-CSF-1R signaling in the macrophage, proteins that are
      rapidly phosphorylated on tyrosine in response to CSF-1 have been identified,
      together with proteins associated with them. Studies on several of these
      proteins, including protein tyrosine phosphates 1C, the c-cbl proto-oncogene
      product, and protein tyrosine phosphatase-phi are discussed.

PMID- 8981358
TI  - Regulation of cell cycle entry and G1 progression by CSF-1.
AB  - Proliferation, differentiation, and survival of monocytes, macrophages, and their
      immediate progenitors is regulated by the macrophage colony-stimulating factor
      (CSF-1). CSF-1 initiates a mitogenic response by binding to its receptor (CSF
      1R), thereby activating the receptor's intrinsic tyrosine kinase activity and
      initiating signaling via multiple effector-mediated pathways. CSF-1 is required
      throughout G1 to ensure entry of bone marrow-derived macrophages into S phase,
      and persistent CSF-1R kinase activity is necessary to the expression of both
      immediate early (e.g., c-fos, c-jun, and c-myc) and delayed early (e.g., D-type
      cyclins) response genes. Ectopic expression of human CSF-1R in different mouse
      cell lines, including fibroblasts, IL-3-dependent myeloid cells, and early pre-B
      cells, confers CSF-1 responsiveness by replacing the cells' requirements for
      other mitogenic growth factors. NIH-3T3 fibroblasts engineered to express a human
      CSF-1 receptor point mutant (CSF-1R [Y809F]) fail to proliferate in response to
      CSF-1 and remain arrested in the early G1 phase of the cell cycle. Despite CSF-1
      dependent transcription of fos and jun family members, c-myc, D-type, and E-type
      G1 cyclin mRNAs are not expressed in the latter cells in response to growth
      factor stimulation. However, enforced expression of c-myc or D-type cyclins, but
      not cyclin E, resensitizes cells bearing CSF-1R (Y809F) to the mitogenic effects
      of CSF-1, enabling them to proliferate continuously in liquid culture and to form
      colonies in agar in response to the growth factor. D-type cyclin mutants
      defective in binding to the retinoblastoma protein (pRB) were unable to rescue
      mutant receptor signaling, suggesting that the ability of D-type cyclin-dependent
      kinases to cancel pRB's growth-suppressive function is necessary for CSF-1
      induced G1 exit. By contrast, cyclin E must function in a different pathway.
      Cells rescued by c-myc were prevented from entering S phase by microinjection of
      antibodies to cyclin D1. Conversely, cyclin D1-rescued cells were inhibited from
      forming CSF-1-dependent colonies in agar when challenged with either a dominant
      negative c-myc mutant or mad, a transcription factor which competes with myc for
      max, its requisite heterodimeric partner. Thus, although the expression of c-myc
      and D-type cyclins is rate limiting for G1 phase progression, their functions are
      interdependent, with both activities being required for mitogenicity.

PMID- 8981359
TI  - CSF-1 and cell cycle control in macrophages.
AB  - Control of cell proliferation involves a finely interwoven network of positive
      and negative cell cycle regulators. Signal transduction pathways linking c-fms
      (CSF-1R) to cellular proliferation and differentiation are being explored. Part
      of the strategy is to use a series of G1 inhibitors to help pinpoint relevant
      targets. Several inhibitors-8Br-cAMP, interferon gamma (IFN gamma), INF
      alpha/beta, lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF alpha),
      and dimethylamiloride-suppress CSF-1-stimulated proliferation in murine bone
      marrow-derived macrophages (BMM) even when added in the mid- to late-G1 phase of
      the cell cycle. The down-modulating effects of the inhibitors on the expression
      of the following cell cycle regulators have been examined: c-myc, cyclin D1 and
      D2, cdk4, Rb phosphorylation, E2F binding activity, ribonucleotide reductase
      subunits, and PCNA. Some differences in the negative control of such regulators
      were found, for example, in the manner in which IFN gamma and cAMP down-regulate
      c-myc expression. Using blocking antibodies and BMM from type I IFN receptor
      knockout mice, it appears that one of these inhibitors, IFN alpha/beta, acts as
      an endogenous inhibitor in CSF-1-treated BMM and is also responsible, at least in
      part, for the inhibition of cell cycle progression by LPS and TNF alpha. Another
      strategy has been to attempt to relate early biochemical changes induced by CSF-1
      to later changes in the G1 phase, partly by studying cycling versus noncycling
      macrophages and partly by using cells expressing c-fms with tyrosine mutations in
      the intracytoplasmic region. CSF-1-mediated effects on the following signal
      transduction molecules in these systems will be described: PI3-kinase, myelin
      basic protein kinases, Erks, and STAT transcription factors.

PMID- 8981360
TI  - Phosphatidylcholine signaling in response to CSF-1.
AB  - The formation of cell membrane following CSF-1 stimulation of a macrophage cell
      line is coordinated with cell cycle progression. The majority of membrane
      phospholipid accumulates during the S phase and results from cell-cycle dependent
      oscillations in the rates of phosphatidylcholine biosynthesis and degradation.
      Both synthesis and degradation are enhanced during the G1 phase, resulting in a
      high rate of phosphatidylcholine turnover. Degradation of phosphatidylcholine
      after CSF-1 stimulation is mediated by a phospholipase C, and the release of
      diacylglycerol during G1 phase is biphasic. The degradation essentially stops
      during the S phase, thus allowing biosynthesis to supply the necessary membrane
      for cell division and doubling. The degradation of phosphatidylcholine during G1
      signals the downstream activation of c-fos and junB transcription and can be
      mimicked by incubation of the macrophage cells with exogenous bacterial
      phospholipase C. In contrast, the expression of c-myc transcripts normally
      associated with CSF-1 stimulation is severely compromised in phospholipase C
      treated cells, indicating that the diacylglycerol signals a pathway distinct from
      the pathway that governs c-myc activation. Constitutive expression of c-myc
      complements phospholipase C activity and permits the growth of cells in the
      presence of exogenous bacterial enzyme and the absence of CSF-1. Protein kinase C
      is not required to mediate the diacylglycerol signal that supports cell growth.
      GTP exchange on Ras is not enhanced, and MAP kinase activity is not stimulated in
      response to phosphatidylcholine degradation by exogenous phospholipase C. The 85
      kDa cytoplasmic phospholipase A2 is activated, however, as well as a novel
      protein we have called p96. Rapid serine phosphorylation of p96 follows
      stimulation of cells with either CSF-1 or exogenous phospholipase C. Analysis of
      the murine cDNA encoding p96 reveals an amino-terminal domain with significant
      similarity to the amino-terminal domain of the Drosophila-disabled gene product
      and a carboxy-terminal domain containing proline-rich sequences characteristic of
      SH3 binding regions. The sequence of p96 suggests an interactive role for this
      unique protein in the CSF-1 signal transduction cascade.

PMID- 8981361
TI  - Structure-function studies on human macrophage colony-stimulating factor (M-CSF).
AB  - M-CSF (CSF-1) can be produced in a variety of structural forms that may affect
      function in vivo. Truncated, nonglycosylated forms of recombinant M-CSF (rM-CSF)
      from E. coli have been refolded in vitro in high yield and shown to be
      functionally equivalent in vitro to glycosylated rM-CSF secreted from mammalian
      cells. An N-terminal domain of 149 amino acids is produced by all of the known M
      CSF mRNA splice variants and is the region responsible for bioactivity observed
      in vitro. Heterodimeric rM-CSFs from different splice variants containing this
      domain were produced in pure form by refolding in vitro, and are fully active,
      but have yet to be observed in vivo. The circulating half-life of truncated M-CSF
      forms injected intravenously into rats increased with the MW of the M-CSF used.
      Large increases in half-life in vivo were observed following chemical addition of
      a single molecule of 10 kD polyethylene glycol to rM-CSF in vitro. The crystal
      structure of rM-CSF revealed that M-CSF is a member of a family of molecules
      related by having a distinctive four-helical-bundle structural core. Site
      directed mutagenesis showed that residues in or near helix A and helix C are
      involved in receptor binding, as reflected by decreased bioactivity and receptor
      binding of certain mutants. A soluble form of the M-CSF receptor, c-fms, was
      produced in a baculovirus/Sf9 expression system and purified to homogeneity. The
      MW of rM-CSF saturated with this soluble receptor was determined by molecular
      sieve chromatography and light scattering. Each dimeric M-CSF molecule appears to
      bind two soluble receptor molecules in vitro, supporting the observation that M
      CSF signaling is linked to receptor dimerization.

PMID- 8981362
TI  - Transcriptional regulation of the mouse CSF-1 gene.
AB  - Research in our laboratory is aimed at understanding the cellular and molecular
      mechanisms that govern colony stimulating factor-1 (CSF-1) gene expression. Our
      hypothesis is that a basal set of trans-acting factors is bound to the CSF-1 gene
      during fibroblast proliferation, resulting in constitutive CSF-1 gene expression.
      Modulation of CSF-1 gene transcription by growth-arrest (decrease) or stimulation
      of growth-arrested fibroblasts (re-initiate) is mediated by changes in the basal
      set of factors bound and/or by the addition of stimulus-specific factors. We have
      extended our hypothesis to include other cell types (monocytes) to determine if
      mechanisms used to control CSF-1 gene expression in fibroblasts are unique or
      represent common nontissue-specific regulatory mechanisms. Analysis of CSF-1-CAT
      reporter constructs in transiently transfected fibroblasts and monocytes was used
      to identify CSF-1 genomic sequences that affect transcriptional activity. DNase I
      protection, electrophoretic mobility shift, and methylation interference assays
      were used to identify the putative cis-acting elements. Results of our study
      suggest multiple trans-acting factors may regulate CSF-1 gene expression; some
      may be tissue specific, while others, such as AP1, CTF/NF1, Sp1, and Sp3, are
      shared in common.

PMID- 8981363
TI  - Regulation of CSF-1 receptor expression.
AB  - Cells of the mononuclear phagocyte lineage possess receptors for macrophage
      colony-stimulating factor (CSF-1) encoded by the c-fms protooncogene and respond
      to CSF-1 with increased survival, growth, differentiation, and reversible changes
      in function. The c-fms gene is itself a macrophage differentiation marker. In
      whole mount analyses of mRNA expression in embryos, c-fms is expressed at very
      high levels on placental trophoblasts. It is detectable on individual cells in
      the yolk sac around 8.5 to 9 days postcoitus, appears on isolated cells in the
      head of the embryo around 9.5 dpc, and appears on numerous cells throughout the
      embryo by day 10.5. The extent of c-fms expression is much greater than for other
      macrophage-specific genes including lysozyme and a macrophage-specific protein
      tyrosine phosphatase. Our studies of the cis-acting elements of the c-fms
      promoter have indicated a key role for collaboration between the macrophage
      specific transcription factor, Pu.1, which functions in determining the site of
      transcription initiation, and other members of the Ets transcription factor
      family. This is emerging as a common pattern in macrophage-specific promoters. We
      have shown that two PU box elements alone can function as a macrophage-specific
      promoter. The activity of both the artificial promoter and the c-fms promoter is
      activated synergistically by coexpression of Pu.1 and another Ets factor, c-Ets
      2. A 3.5kb c-fms exon 2 promoter (but not the 300bp proximal promoter) is also
      active in a wide diversity of tumor cell lines. The interesting exception is the
      melanoma cell line K1735, in which the promoter is completely shut down and
      expression of c-fms causes growth arrest and cell death. The activity of the exon
      2 promoter in these nonmacrophages is at least as serum responsive as the classic
      serum-responsive promoter of the c-fos gene. It is further inducible in
      nonmacrophages by coexpression of the c-fms product. Unlike other CSF-1/c-fms
      responsive promoters, the c-fms promoter is not responsive to activated Ras even
      when c-Ets-2 is coexpressed. In most lines, production of full length c-fms is
      prevented by a downstream intronic terminator, but in Lewis lung carcinoma, read
      through does occur, and expression of both c-fms and other macrophage-specific
      genes such as lysozyme and urokinase becomes detectable in conditions of serum
      deprivation.

PMID- 8981364
TI  - Role of colony-stimulating factor-1 in reproduction and development.
AB  - The CSF-1 null mouse, osteopetrotic, has provided a powerful model in which to
      study the biological functions of CSF-1. In this review, I will describe our
      studies that have used this mouse model to determine the impact of a lack of CSF
      1 on developmental processes and in reproduction. A role for CSF-1 in
      reproduction was originally suggested by the sex steroid hormone-regulated
      uterine epithelial synthesis of CSF-1 and the expression of its receptor in
      trophoblast and decidual cells. Studies on the fertility of CSF-1 deficient
      osteopetrotic mice (csfmop/csfmop) mice confirmed this suggestion and in addition
      revealed an unexpected function for CSF-1 in male fertility. In both sexes, CSF-1
      appears to regulate gonadal steroidogenesis, probably through its action on
      macrophages that are abundant throughout the ovary and testis. In the female, CSF
      1 affects ovulation in vivo and in vitro, and impacts the preimplantation embryo,
      increasing both its rate of development and the number of trophectodermal cells
      in the blastocyst. CSF-1 also has a role in mammary gland development during
      pregnancy, since at mid-gestation in csfmop/csfmop mice, ductal branching is
      impaired, and after partiturition, there is a failure to switch to lactation. The
      relative failure of csfmop/csfmop mice to respond to external stimuli also
      suggested a role for CSF-1 in the brain. CSF-1 mRNA is expressed in a regional
      specific manner in the brain through development whilst the CSF-1 receptor is
      expressed throughout the brain in microglia. CSF-1 is neurotrophic in embryonic
      neuronal cultures and its absence in csfmop/csfmop mice results in severe electro
      physiological abnormalities in the cortex. This suggests that CSF-1 is a
      neurotrophic factor acting through the microglia. The pleiotropic roles for CSF-1
      in reproduction and in the brain suggest that CSF-1 exerts many of its action
      through the trophic activities of cells of the mononuclear phagocytic lineage.

PMID- 8981365
TI  - Relative role of CSF-1, MCP-1/JE, and RANTES in macrophage recruitment during
      successful pregnancy.
AB  - It has been previously demonstrated that macrophage colony stimulating factor
      (CSF-1) is produced by uterine epithelial cells in response to estrogen and
      progesterone. Studies in normal and op/op mice demonstrated that accumulation of
      a portion of the uterine macrophage population could be attributed to the
      chemotactic properties of CSF-1. Op/op mice exhibit greatly reduced rates of
      fertility, but successful pregnancy is not completely blocked. Also, uteri from
      op/op mice are not completely macrophage deficient. There are two possible
      explanations for this. One is that not all tissue macrophages are recruited from
      the bone marrow pool; some may be derived from primitive mesenchyme.
      Alternatively, tissue macrophages may be recruited from the bone marrow pool
      through expression of other type 1 chemokines such as JE, RANTES, MIP-1 alpha,
      MIP-1 beta, IP-10, and KC. Both RANTES and JE are expressed at higher levels than
      CSF-1 during early pregnancy. The variable expression and relative role of these
      various chemokines in pregnancy was addressed by measuring mRNA expression during
      the first 8 days of pregnancy and in a pseudopregnant model. The expression of
      these various genes relative to macrophage numbers and macrophage distribution
      will be discussed. The relative role of these various factors in preparing the
      uterus for blastocyst implantation will be discussed.

PMID- 8981366
TI  - CSF-1 and its receptor in breast carcinomas and neoplasms of the female
      reproductive tract.
AB  - The expression and function of CSF-1 and its receptor were studied in tumors of
      the human breast, ovary, and endometrium. CSF-1 and its receptor, initially
      implicated as essential to normal monocyte development and trophoblastic
      implantation, have been more recently shown to be expressed by carcinomas of the
      breast and other epithelia of the female reproductive tract where activation of
      the receptor by ligand produced either by the tumor cells or by stromal elements
      stimulates tumor cell invasion by a urokinase-dependent mechanism. Breast
      carcinomas express wild-type CSF-1 receptors (CSF-1R) at levels comparable to
      those observed in trophoblast and monocytes. Ovarian and endometrial carcinomas
      express significantly lower levels of wild-type, functional CSF-1Rs, while
      ovarian carcinomas also express unusual transcripts that diverge from the wild
      type CSF-1R transcript in their 5' extracellular domain sequences. Tumor cell
      expression of CSF-1R is under the control of several steroid hormones
      (glucocorticoids and progestins) and the binding of several bHLH transcription
      factors, while tumor cell expression of CSF-1 appears to be regulated by other
      hormones, some of which are involved in normal lactogenic differentiation. In
      addition, tumor cells often produce CSF-1 at such high levels that the cytokine
      spills into the extracellular fluid and circulation. Measurements of circulating
      levels of CSF-1 have proved useful in patients with ovarian, endometrial, and
      breast carcinoma both for disease detection and monitoring of response to
      therapy. CSF-1 and its receptor appear to be an important receptor/ligand pair in
      the biology of breast cancers and tumors of the female reproductive tract where
      they may regulate functions similar to those they control during macrophage
      activation and placental implantation.

PMID- 8981367
TI  - Role of CSF-1 in bone and bone marrow development.
AB  - There is a close interaction between the processes involved in osteogenesis and
      hemopoiesis. In developing bone, the osteoclasts, cells of hemopoietic origin,
      resorb and invade the calcified cartilage rudiment. As a result, the primitive
      marrow cavity is formed and hemopoiesis initiates. Osteogenic cells-osteoblasts
      and osteocytes-control the development and activity of the osteoclasts through
      the local release of factors. One factor responsible for this osteoblast
      osteoclast interaction is colony-stimulating factor-1 (CSF-1). Studies performed
      on the osteopetrotic op/op mouse mutant have established that this factor is
      essential for proliferation and differentiation of the osteoclasts. Expression of
      CSF-1 receptors by mature osteoclasts and osteoclast precursors strongly suggests
      that CSF-1 action is exerted directly on cells of this lineage. In vivo, CSF-1
      synthesis by osteoblasts is temporally and spatially related to sites of
      osteoclast development. Thus CSF-1 may represent one of the factors responsible
      for coupling hemopoiesis to osteogenesis. In vitro, osteoblasts express at least
      4 transcripts encoding either a secreted or a membrane-bound form of CSF-1. At
      the protein level, osteoblasts in vitro synthesize the membrane-bound form and
      secrete the majority of CSF-1 as a proteoglycan, a small fraction of which is
      integrated into the matrix. These different molecular forms may locally restrict
      the biological action of this cytokine. Indeed, injection of recombinant human
      CSF-1 in op/ op mutants does not correct the osteoclast deficiency in the
      metaphyseal spongiosa of long bones, and sclerosis persists at this site.
      Similarly, the deficiency of some tissue macrophage populations in op/op mice is
      only partially or not at all corrected by injection of CSF-1. The expression of
      CSF-1 receptors by mature osteoclasts may imply that CSF-1 also influences their
      bone resorbing activity. Indeed, CSF-1 has been shown to induce osteoclast
      fusion, spreading, and survival. These findings suggest that CSF-1 is essential
      for the proliferation, differentiation, activity, and survival of tissue
      macrophages and osteoclasts, cells involved in tissue turnover. Furthermore, they
      corroborate the view that both osteoclasts and tissue macrophages stem from a CSF
      1-dependent common precursor along the macrophage lineage.

PMID- 8981368
TI  - Macrophage differentiation and granulomatous inflammation in osteopetrotic mice
      (op/op) defective in the production of CSF-1.
AB  - Since the osteopetrotic (op/op) mouse was demonstrated to have a mutation within
      the coding region of the CSF-1 gene itself, it serves as a model for
      investigating the differentiation mechanism of macrophage populations in the
      absence of functional CSF-1. The op/op mice were severely monocytopenic and
      showed marked reduction and abnormal differentiation of tissue macrophages.
      Osteoclasts as well as marginal metallophilic macrophages and marginal zone
      macrophages in the spleen were absent. Most of the tissue macrophages were
      reduced in number and ultrastructurally immature. However, the degree of
      reduction in numbers of macrophages in the mutant mice was variable among
      tissues, suggesting that the heterogeneity of macrophages was generated by their
      different dependency on CSF-1. After daily CSF-1 injection, the numbers of
      monocytes, tissue macrophages, and osteoclasts were remarkably increased, and the
      macrophages showed morphological maturation. However, the numbers of macrophages
      in the ovary, uterus, and synovial membrane were not increased. In the bone
      marrow, macrophage precursors detected by monoclonal antibody ER-MP58
      proliferated and differentiated into preosteoclasts and osteoclasts. In the
      spleen, marginal metallophilic macrophages and marginal zone macrophages
      developed slowly. In this manner, CSF-1 plays an important role in the
      development, proliferation, and differentiation of certain tissue macrophage
      populations and osteoclasts. In the op/op mice, Kupffer cells proliferated,
      transformed into epithelioid cells and multinucleated giant cells, and
      participated in glucan-induced granuloma formation. In CSF-1-treated op/op mice,
      the process of granuloma formation was similar to that in normal littermates due
      to increased monocytopoiesis and monocyte influx into the granulomas. These
      results indicate that CSF-1 is a potent inducer of the development and
      differentiation of CSF-1-dependent monocyte/macrophages, and that CSF-1
      independent macrophages also play an important role in granuloma formation.

PMID- 8981369
TI  - Immunoreactive macrophage colony-stimulating factor is increased in
      atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits after
      recombinant human macrophage colony-stimulating factor therapy.
AB  - Infiltration of monocytes into arteries is an early event in the pathogenesis of
      atherosclerosis. This recruitment is interpreted as enhancing lesion development,
      but it could also be a host response limiting lipid accumulation. The ability of
      macrophages to limit cholesterol uptake, however, can be reduced by the impaired
      mobility and metabolic activity associated with foam cell development. As lesions
      enlarge, foam cells die and become the nidus for the necrotic core. Treatments to
      improve viability might improve foam cell function and promote regression.
      Macrophage colony-stimulating factor (M-CSF) is vital to monocyte/macrophage
      differentiation, proliferation, and activation. We found that foam cells of
      Watanabe heritable hyperlipidemic (WHHL) rabbits had faint staining for M-CSF.
      Treatment of rabbits with recombinant human M-CSF (rhM-CSF) increased M-CSF
      staining, which correlated with reduced cholesterol content of these foam cells.

PMID- 8981370
TI  - Growth and differentiation signals regulated by the M-CSF receptor.
AB  - The normal proto-oncogene c-fms encodes the macrophage growth factor (M-CSF)
      receptor involved in growth, survival, and differentiation along the monocyte
      macrophage lineage of hematopoietic cell development. A major portion of our
      research concerns unraveling the temporal, molecular, and structural features
      that determine and regulate these events. Previous results indicated that c-fms
      can transmit a growth signal as well as a signal for differentiation in the
      appropriate cells. To investigate the role of the Fms tyrosine
      autophosphorylation sites in proliferation vs. differentiation signaling, four of
      these sites were disrupted and the mutant receptors expressed in a clone derived
      from the myeloid FDC-P1 cell line. These analyses revealed that: (1) none of the
      four autophosphorylation sites studied (Y697, Y706, Y721, and Y807) are essential
      for M-CSF-dependent proliferation of the FDC-P1 clone; (2) Y697, Y706, and Y721
      sites, located in the kinase insert region of Fms, are not necessary for
      differentiation but their presence augments this process; and (3) the Y807 site
      is essential for the Fms differentiation signal: its mutation totally abrogates
      the differentiation of the FDC-P1 clone and conversely increases the rate of M
      CSF-dependent proliferation. This suggests that the Y807 site may control a
      switch between growth and differentiation. The assignment of Y807 as a critical
      site for the reciprocal regulation of growth and differentiation may provide a
      paradigm for Fms involvement in leukemogenesis, and we are currently
      investigating the downstream signals transmitted by the tyrosine-phosphorylated
      807 site. In Fms-expressing FDC-P1 cells, M-CSF stimulation results in the rapid
      (30 sec) tyrosine phosphorylation of Fms on the five cytoplasmic tyrosine
      autophosphorylation sites, and subsequent tyrosine phosphorylation of several
      host cell proteins occurs within 1-2 min. Complexes are formed between Fms and
      other signal transduction proteins such as Grb2, Shc, Sos1, and p85. In addition,
      a new signal transduction protein of 150 kDa is detectable in the FDC-P1 cells.
      The p150 is phosphorylated on tyrosine, and forms a complex with Shc and Grb2.
      The interaction with Shc occurs via a protein tyrosine binding (PTB) domain at
      the N-terminus of Shc. The p150 is not detectable in Fms signaling within
      fibroblasts, yet the PDGF receptor induces the tyrosine phosphorylation of a
      similarly sized protein. In hematopoietic cells, this protein is involved in
      signaling by receptors for GM-CSF, IL-3, KL, MPO, and EPO. We have now cloned a
      cDNA for this protein and found at least one related family member. The related
      family member is a Fanconia Anemia gene product, and this suggests potential ways
      the p150 protein may function in Fms signaling.

PMID- 8981371
TI  - Role of c-Src in cellular events associated with colony-stimulating factor-1
      induced spreading in osteoclasts.
AB  - We and others have observed that in response to treatment with Colony Stimulating
      Factor-1 (CSF-1) neonatal rat osteoclasts demonstrate rapid cytoplasmic
      spreading. The receptor for CSF-1, c-Fms, is expressed in osteoclasts, possesses
      intrinsic tyrosine-kinase activity, and signals via rapid phosphorylation of
      selected proteins. It has been reported previously that c-Src becomes tyrosine
      phosphorylated following CSF-1 treatment of fibroblasts overexpressing c-Fms. We
      therefore examined the cellular events associated with CSF-1-induced spreading in
      osteoclasts and what role, if any, c-Src played in these processes. Confocal
      microscopic studies using phosphotyrosine (P-tyr) monoclonal antibodies
      demonstrated that CSF-1 induced a significant dose- and time-dependent increase
      in P-tyr labeling of neonatal rat osteoclasts. Phalloidin staining was consistent
      with partial to complete disassembly of the actin attachment ring with
      redistribution of actin to the spreading cytoplasmic edge of the cell.
      Quantitation of cellular F-actin using NBD-phallicidin confirmed a decrease in
      polymerized actin following exposure to CSF-1. In contrast, CSF-1 failed to
      induce any cytoplasmic spreading in osteoclasts isolated from mice with targeted
      disruption of the src gene. Further, in src- osteoclasts no well defined
      attachment ring could be identified. To investigate cell-signaling events
      associated with osteoclast spreading, detergent lysates were made from purified
      multinucleated osteoclast-like cells (OCLs) obtained by coculturing murine bone
      marrow and osteoblasts with calcitriol. Western blot analyses of lysates from
      control and CSF-1-treated normal cells indicated that several proteins were
      specifically phosphorylated in response to CSF-1, most notably proteins of 165,
      60, and 85-90 kDa. Immunoprecipitation studies revealed that the 165 and 60 kDa
      proteins were, respectively, c-Fms and c-Src. The c-Src kinase activity was
      increased 2.9-fold following CSF-1 treatment. The 85-90 kDa protein is as yet
      unidentified. Since activated receptor tyrosine kinases may induce spreading in
      part by reducing phosphoinositol 4,5-bisphosphate (PIP2) binding to actin
      associated proteins, a monoclonal antibody to PIP2 was used to assess the nature
      of PIP2 binding proteins in OCLs. Proteins of 85-90 kDa, 43 kDa, and 30 kDa were
      consistently demonstrated to bind PIP2. Further, the PIP2 content of the 85-90
      kDa protein appeared to decrease with CSF-1 treatment. Whether this protein
      represents the phosphoprotein of the same M.W. is unclear. We also examined the
      effect of CSF-1 on the PIP2 content of alpha-actinin. Alpha-actinin showed low
      level PIP2 binding, which was demonstrable only after immuno-precipitation and
      did not change with CSF-1 treatment. However, CSF-1 did cause a significant
      decline in the phosphotyrosine content of alpha-actinin. In contrast, in src-
      OCLs, CSF-1 induced more prolonged phosphorylation of c-Fms, and the 85-90 kDa
      protein was markedly hypophosphorylated. Further, alpha-actinin did not
      dephosphorylate in src- cells. We conclude that CSF-1-induced osteoclast
      spreading is accompanied by rapid reorganization of the actin cytoskeleton and
      phosphorylation of several cellular substrates, including c-Fms and c-Src. PIP2
      binding to at least one protein appears to decrease with CSF-1 treatment, which
      may favor actin depolymerization. The reduced tyrosine phosphorylation of alpha
      actinin could effect its ability to bind to actin. Thus c-Src may play an
      important role in these cellular events since in its absence, osteoclasts do not
      spread and signaling events downstream are altered. Whether these changes relate
      in part to the basal abnormalities in the cytoskeletal organization of src-
      osteoclasts remains to be determined.

PMID- 8981372
TI  - Analogical transfer is effective in a serial reaction time task in Parkinson's
      disease: evidence for a dissociable form of sequence learning.
AB  - Several studies of procedural learning in Parkinson's disease (PD) have
      demonstrated that these patients are impaired with respect to age-matched control
      subjects. In order to examine more closely the specific impairment, we considered
      three dimensions along which a procedural learning task could vary. These are:
      (1) implicit vs explicit learning, (2) instance vs rule learning, and (3)
      learning with internal vs external error correction. We consider two hypotheses
      that could explain the impairments observed in PD for different types of explicit
      motor learning: (H1) an impairment related to the acquisition of rules vs
      specific instances, and (H2) an impairment in learning when no explicit error
      feedback is provided. In order to examine the condition of rule learning with
      external error feedback, we developed a modified version of the serial reaction
      time (SRT) protocol that tests analogical transfer in sequence learning (ATSL).
      Reaction times are measured for responses to visual stimuli that appear in
      several different repeating sequences. While these isomorphic sequences are
      different, they share a common rule. Verbatim learning of a sequence would result
      in negative transfer from one sequence to a different one, while rule learning
      would result in positive transfer. Parkinson's patients and age-matched controls
      demonstrate significant acquisition and positive transfer of the rule between
      sequences. Our results demonstrate that PD patients are capable of learning and
      transferring rule or schema-based representations in an explicit learning format,
      and that this form of learning may be functionally distinct from learning
      mechanisms that rely on representations of the verbatim or statistical structure
      of sequences.

PMID- 8981373
TI  - Spatial memory deficits in patients with unilateral damage to the right
      hippocampal formation.
AB  - Patients with unilateral temporal lobe damage resulting from intractable temporal
      lobe epilepsy (TLE, n = 30) or from temporal lobe resection (temporal lobectomy,
      TLR, n = 47) were investigated on the Nine-box Maze. The task, analogous to the
      radial arm maze, was designed to compare spatial mapping and working memory
      theories of the functions of the hippocampus. The task provides measures of
      spatial, object, working and reference memory, incorporated into a within
      subjects design. The spatial component was designed to encourage the formation of
      allocentric rather than egocentric spatial representations. Spatial memory
      deficits were found (across working and reference memory components) in both TLE
      and TLR patients with right temporal lobe damage, with intact spatial memory in
      patients with corresponding left temporal lobe damage. Performance on the matched
      non-spatial (object) working memory component was equal to healthy controls for
      all groups. However all patient groups showed a deficit on object reference
      memory. These findings are discussed in relation to the underlying temporal lobe
      pathology and particularly atrophy of the hippocampal formation. Overall, the
      results support the cognitive mapping theory of hippocampal function, with the
      demonstration of a selective (and probably allocentric) spatial memory deficit in
      patients with right hippocampal damage.

PMID- 8981374
TI  - Word-stem completion priming for perceptually and conceptually encoded words in
      patients with Alzheimer's disease.
AB  - This study examined whether the frequently reported word-stem completion priming
      deficit of Alzheimer's disease (AD) patients could be characterized as either a
      semantic encoding deficit or a conceptual priming deficit. AD patients and normal
      elderly control subjects studied words in two conditions: (1) reading visually
      presented words aloud, which maximizes perceptual encoding of seen words, and (2)
      generating words aloud from definitions, which maximizes conceptual encoding of
      words not seen but retrieved on the basis of semantic context. Recognition
      accuracy was greater for words that were generated at study, and word-stem
      completion priming was greater for words that were read at study. For the AD
      patients, recognition accuracy was impaired and word-stem completion priming was
      intact for words encoded in both conditions. The findings are discussed in terms
      of discrepant results about word-stem completion priming in AD.

PMID- 8981375
TI  - Interhemispheric relations in hierarchical perception: a second look.
AB  - This study reevaluates the role of interhemispheric interactions in the
      consistency effect (global interference with local decisions) in hierarchical
      perception. In an earlier study, Robertson et al. [22] (Neuropsychology, Vol. 7,
      pp. 325-342, 1993) tested three split-brain patients on a hierarchical perception
      task in which stimuli, consisting of large (global) letters made up of smaller
      (local) letters, were unilaterally or bilaterally presented for identification.
      They found that, in general, the consistency effect did not occur in split-brain
      patients and argued that the effect is interhemispheric and normally mediated by
      the corpus callosum. We repeated the experiment with new stimuli in two of the
      same split-brain patients. We found that both patients demonstrated evidence for
      global interference, implying that the neocortical commissures are not necessary
      for eliciting the consistency effect in hierarchical perception.

PMID- 8981376
TI  - Untroubled musical judgement of a performing organist during early epileptic
      seizure of the right temporal lobe.
AB  - The case of a professional musician with a right temporal lobe epilepsy is
      presented. Whilst playing an organ concert (John Stanley's Voluntary VIII, Op.
      5), he suffered a complex partial seizure. The recorded concert performance (with
      the seizure) was analysed and compared with other available exercise records and
      with the composition. The musical analysis of the seizure-induced variations
      reveals that at the beginning of the seizure, the left hand started to become
      unprecise in time and deviated from the score, whereas the right hand remained
      faultless at this time. With increasing duration of the seizure discharge, the
      dissociation of both hands from the score increased but the right hand
      compensated for the errors of the left hand in a musically meaningful way, i.e.
      with the aim to compensate for the seizure-induced errors of the left hand. The
      case illustrates untroubled musical judgement during epileptic activity in the
      right temporal lobe at the beginning of the seizure. Whereas the temporal
      formation of the performance was markedly impaired, the ability of improvisation
      in the sense of a 'perfect musical solution' to errors of the left hand-remained
      intact.

PMID- 8981377
TI  - Reaching with cerebral tunnel vision.
AB  - We studied reaching movements in a 48-year-old man with bilateral lesions of the
      calcarine cortex which spared the foveal representation and caused severe tunnel
      vision. Three-dimensional (3D) reconstruction of brain MR images showed no
      evidence of damage beyond area 18. The patient could not see his hand during
      reaching movements, providing a unique opportunity to test the role of peripheral
      visual cues in limb control. Optoelectronic recordings of upper limb movements
      showed normal hand paths and trajectories to fixated extrinsic targets. There was
      no slowing, tremor, or ataxia. Self-bound movements were also preserved. Analyses
      of limb orientation at the endpoints of reaches showed that the patient could
      transform an extrinsic target's visual coordinates to an appropriate upper limb
      configuration for target acquisition. There was no disadvantage created by
      blocking the view of the reaching arm. Moreover, the patient could not locate
      targets presented in the hemianopic fields by pointing. Thus, residual
      nonconscious vision or 'blindsight' in the aberrant fields was not a factor in
      our patient's reaching performance. The findings in this study show that
      peripheral visual cues on the position and velocity of the moving limb are not
      critical to the control of goal directed reaches, at least not until the hand is
      close to target. Other cues such as kinesthetic feedback can suffice. It also
      appears that the visuomotor transformations for reaching do not take place before
      area 19 in humans.

PMID- 8981378
TI  - Asperger's syndrome and memory: similarity to autism but not amnesia.
AB  - Two experiments are described in which the memory of adults with Asperger's
      syndrome is compared with that of verbal IQ controls. The results of the first
      experiment showed that the Asperger subjects resembled autistic adults and
      children in their failure to use category information to aid their free recall.
      In the second experiment, both groups of subjects showed similar priming effects
      in an implicit stem completion task and similar performance on an explicit cued
      recall task. Moreover, both groups also showed more priming for items that they
      had read at study and better recall for items that they had to generate at study,
      suggesting that the cued recall of the Asperger subjects did not result from
      contamination by automatic or involuntary processes.

PMID- 8981379
TI  - Long-term memory in mental retardation: evidence for a specific impairment in
      subjects with Down's syndrome.
AB  - This study aimed at investigating long-term memory functioning in Down's syndrome
      subjects (DS) as compared to individuals with mental retardation of different
      etiology (MR) and mental-age matched normal children (MA). For this purpose,
      tests of verbal and visuo-perceptual explicit memory and a verbal repetition
      priming task were administered to 15 DS, 15 MR and 30 MA subjects. Our results
      document comparable verbal priming in the three groups. As for explicit memory,
      normal children performed better than MR individuals, and these, in turn, better
      than DS subjects. Compared to MR subjects, DS subjects were particularly
      deficient in organizing verbal material according to its categorical structure
      and in actively retrieving stored information. These results support a view
      positing heterogeneity of neuropsychological deficits across distinct etiology MR
      groups.

PMID- 8981381
TI  - Electrophysiological responses from a temporal order continuum in the newborn
      infant.
AB  - Auditory Evoked Responses (AERs) were used to investigate discrimination of
      temporal order differences in eight male and eight female newborn infants. The
      temporal lags in two-tone non-speech stimuli-known as tone-onset time (TOT)
      modeled the temporal delay of voicing-onset time (VOT), an important cue for
      voicing contrasts. Analyses on peak amplitude measures and principal component
      scores indicated that the amplitude of the second negative AER deflection (N530)
      recorded from the left and right parietal leads changed abruptly as TOT values
      increased from +20 to +40 msec. However, no differences were noted between tokens
      that belonged in the same adult perceptual categories. A similar pattern of
      variability was observed for the amplitude of the first major negative peak
      (N200). Our findings indicate that the neurophysiological mechanisms underlying
      categorical-like distinctions of a temporal voicing cue used in speech perception
      may have an innate basis. Since both hemispheres produced similar responses at
      birth, the present data suggest that brain mechanisms involved in temporal order
      processing undergo significant reorganization during the first years of life.

PMID- 8981380
TI  - Does the previous trial affect lateralized lexical decision?
AB  - We investigated the effect of previous trial variables on performance in the
      current trial in a lexical decision task with unilateral presentation of one
      letter string or bilateral simultaneous presentation of two different letter
      strings, one cued to be processed (target) and the other uncued, to be ignored
      (distractor). The variables included correctness of the previous trial, visual
      hemifield and wordness of the previous trial, and presentation mode of the
      previous trial (unilateral or bilateral). An incorrect response on the previous
      trial enhanced the accuracy in the current trial only in the left visual field
      (LVF). A previous LVF target produced faster correct responses to LVF targets in
      the current trial and LVF word recognition was more accurate when the previous
      LVF target was a word rather than a nonword. Target processing in the current
      trial was not inhibited or facilitated if the target belonged to the same
      response category as the unattended stimulus in the previous trial (absence of
      "negative priming'). Taken together, our data suggest that previous trial effects
      in lateralized lexical decision are stronger for word decisions in the LVF, and
      may account for the inconsistency of the wordness effect in the LVF across
      different lateralized lexical decision experiments. Our data also suggest that
      behavioral laterality experiments are well advised to use random sequences that
      change across subjects in order to minimize previous trial effects.

PMID- 8981382
TI  - Visual scan paths are abnormal in deluded schizophrenics.
AB  - One explanation for delusion formation is that they result from distorted
      appreciation of complex stimuli. The study investigated delusions in
      schizophrenia using a physiological marker of visual attention and information
      processing, the visual scan path-a map tracing the direction and duration of gaze
      when an individual views a stimulus. The aim was to demonstrate the presence of a
      specific deficit in processing meaningful stimuli (e.g. human faces) in deluded
      schizophrenics (DS) by relating this to abnormal viewing strategies. Visual scan
      paths were measured in acutely-deluded (n = 7) and non-deluded (n = 7)
      schizophrenics matched for medication, illness duration and negative symptoms,
      plus 10 age-matched normal controls. DS employed abnormal strategies for viewing
      single faces and face pairs in a recognition task, staring at fewer points and
      fixating non-feature areas to a significantly greater extent than both control
      groups (P < 0.05). The results indicate that DS direct their attention to less
      salient visual information when viewing faces. Future paradigms employing more
      complex stimuli and testing DS when less-deluded will allow further clarification
      of the relationship between viewing strategies and delusions.

PMID- 8981383
TI  - A PET study of 5-HT2 and D2 dopamine receptor occupancy induced by olanzapine in
      healthy subjects.
AB  - Olanzapine is a new antipsychotic drug with affinity for 5-HT2, D2, D1, and
      muscarinic receptors. Positron emission tomography and the radioligands
      [11C]raclopride and [11C]NMSP were used to measure D2 and 5-HT2 receptor
      occupancy in three healthy subjects after 10 mg olanzapine orally. After seven
      hours D2 receptor occupancy was 63%, 62% and 59%, respectively. After 9.5 hours 5
      HT2 receptor occupancy was 74%, 86% and 92%. D2 and 5-HT2 receptor occupancy was
      comparable to that found in patients continuously treated with clozapine.
      Clinical efficacy has been demonstrated for olanzapine in the dose range 5 to 15
      mg per day. Extrapolation from our present observations after a 10 mg single-dose
      suggest, that at the lower end of the clinically examined dose range the D2 and 5
      HT2 receptor occupancy should be similar to that induced by standard doses of
      clozapine. Detailed evaluation of the dose-response characteristics of olanzapine
      and direct clinical comparison to clozapine will thus provide valuable leads to
      the clarification of atypical antipsychotic action.

PMID- 8981384
TI  - Effects of genetically determined S-mephenytoin 4-hydroxylation status and
      cigarette smoking on the single-dose pharmacokinetics of oral alprazolam.
AB  - This study examines the effects of genetically determined S-mephenytoin 4
      hydroxylation capacity and cigarette smoking on the single-dose pharmacokinetics
      of oral alprazolam in 12 healthy male volunteers. Six subjects each were
      extensive metabolizers (EMs) and poor metabolizers (PMs) of S-mephenytoin 4
      hydroxylation. Seven subjects were smokers (> 10 cigarettes/day), and five were
      nonsmokers, according to their self-reports. Each subject took a single oral dose
      of 0.8 mg of alprazolam, and blood samples were collected up to 48 hours
      postdose. Psychomotor function was assessed at times of blood samplings using the
      Digit Symbol Substitution Test (DSST), Visual Analog Scale (VAS), and UKU Side
      Effect Rating Scale. Plasma alprazolam concentrations were measured by a high
      performance liquid chromatography assay. None of the mean pharmacokinetic
      parameters was significantly different between the EM and PM phenotype groups.
      Although the mean elimination half-life was significantly shorter in the smoker
      group (p < .01) than in the nonsmoker group (13.1 +/- 2.9 vs. 20.0 +/- 2.7 hours,
      mean +/- SD), other pharmacokinetic parameters did not differ significantly
      between the two groups. Psychomotor function parameters did not differ
      significantly either between the EM and PM groups or between the nonsmoker and
      smoker groups. The present study thus suggests that neither S-mephenytoin 4
      hydroxylation status nor self-reports of extensive cigarette smoking has a major
      impact on the metabolism of alprazolam in humans.

PMID- 8981385
TI  - Cognitive and behavioral effects of cholinergic, dopaminergic, and serotonergic
      blockade in humans.
AB  - The purpose of this study was to investigate the cognitive and behavioral effects
      of anticholinergic, antidopaminergic, and antiserotonergic agents given alone and
      in combination to normal volunteers. Twelve young male volunteers took part in
      this double-blind, randomized, placebo-controlled, crossover study of six drug
      conditions, each administered on separate days [haloperidol (2 mg p.o.) +/
      scopolamine (0.5 mg i.v.), metergoline (4 mg p.o.) +/-scopolamine (0.5 mg i.v.),
      placebo, and scopolamine alone (0.5 mg i.v.)]. Scopolamine-induced sedation (p <
      .01), slowed information processing (p < .01) and impaired new learning and
      memory (p < .01), but did not affect attention or retrieval from semantic memory.
      Given alone, haloperidol selectively impaired the ability to rapidly switch
      cognitive sets (p < .05), and metergoline decreased pupil size (p < .01) but did
      not induce cognitive deficits. In combination with scopolamine, neither
      haloperidol nor metergoline produced a worsening of the subjects' cognitive
      performance above and beyond that seen with scopolamine alone. On the contrary, a
      trend (p < .10) for haloperidol to reverse some of the scopolamine-induced
      exacerbation of verbal short-term forgetting was observed. The data indicate that
      scopolamine and haloperidol can independently and selectively affect cognition
      and that at the doses tested in this study no synergistic exacerbation of
      cognitive functioning was found when cholinergic blockage was coupled with
      dopaminergic or serotonergic blockade.

PMID- 8981386
TI  - Effects of lithium and carbamazepine on thyroid hormone metabolism in rat brain.
AB  - The effects of lithium (LI) and carbamazepine (CBM) on thyroid hormone metabolism
      were investigated in 11 regions of the brain and three peripheral tissues in rats
      decapitated at three different times of day (4:00 A.M., 1:00 P.M., and 8:00
      P.M.). Interest was focused on the changes in the two enzymes that catalyze: (1)
      the 5'deiodination of T4 to the biologically active T3, i.e., type II
      5'deiodinase (5'D-II) and (2) the 5 (or inner-ring) deiodination of T3 to the
      biologically inactive 3'3-T2, i.e., type III 5 deiodinase (5D-III). A 14-day
      treatment with both LI and CBM induced significant reductions in 5D-III activity.
      However, 5'D-II activity was elevated by CBM and reduced by LI, both administered
      in concentrations leading to serum levels comparable with those seen in the
      prophylactic treatment of affective disorders. The effects were dose dependent,
      varied according to the region of the brain under investigation, and strongly
      depended on the time of death within the 24-hour rhythm. The consequences of
      these complex effects of LI and CBM on deiodinase activities for thyroid hormone
      function in the CNS and also their possible involvement in the mechanisms
      underlying the mood-stabilizing effects of both LI and CBM remain to be
      investigated.

PMID- 8981387
TI  - Haloperidol- and clozapine-induced enhancement of latent inhibition with extended
      conditioning: implications for the mechanism of action of neuroleptic drugs.
AB  - Latent inhibition (LI) refers to retarded conditioning to a stimulus as a
      consequence of its nonreinforced preexposure. LI is impaired in acute
      schizophrenic patients and in rats treated with amphetamine. Neuroleptic drugs
      enhance LI, and this effect is selective and specific for this class of drugs.
      The present experiments tested the proposition that neuroleptic-induced
      enhancement of LI stems from decreased capacity of stimulus-preexposed animals to
      switch responding according to the new stimulus-reinforcement contingency in the
      conditioning stage. LI was assessed using an off-baseline conditioned emotional
      response (CER) procedure in rats licking for water, consisting of three stages:
      preexposure to the-to-be conditioned stimulus, tone; conditioning, in which the
      preexposed stimulus was paired with a foot-shock; and test, in which LI was
      indexed by animals' degree of suppression of licking during tone presentation.
      Whereas in previous studies that demonstrated LI enhancement by neuroleptics,
      preexposure consisted of 10 to 40 tones, and conditioning included two tone-shock
      pairings, the present experiments used 40 tone preexposures, followed by an
      extended conditioning stage with five tone-shock pairings. It was expected that
      under these conditions no LI effect would be evident in untreated animals, but
      that animals treated with a neuroleptic drug, either during the entire LI
      procedure or only in conditioning, would show LI. Experiments 1 and 2 showed that
      LI was obtained in rats treated with haloperidol (0.1 mg/kg in experiment 1, 0.03
      and 0.2 mg/kg in experiment 2) but not in the untreated controls. Experiment 3
      showed that the same outcome was obtained when haloperidol (0.1 mg/kg)
      administration was confined to the conditioning stage. Experiment 4 showed that
      clozapine (5 mg/kg)-treated animals showed LI when the drug was confined to
      conditioning, but not to the preexposure stage. The implications of these results
      for the mechanism of action of neuroleptic drugs are discussed.

PMID- 8981388
TI  - Sleep in schizophrenia: a polysomnographic study on drug-naive patients.
AB  - A slow wave sleep (SWS) deficit and a shortened rapid eye movement (REM) sleep
      latency are commonly reported in schizophrenic patients. However, most of these
      patients have been off neuroleptic medication for only a short period of time.
      Therefore, the reported sleep alterations may be due to residual drug effects. We
      polysomnographically investigated 22 drug-naive patients with a schizophrenic
      disorder, paranoid type, and 20 normal controls. In addition, we assessed the
      ventricular brain ratio (VBR) by means of computed assisted tomography. Except
      for a prolonged sleep onset latency, increased wake time and decreased stage 2
      sleep, the patients showed a sleep pattern, i.e., of SWS and REM sleep,
      comparable with that of controls. The VBR was increased in 71% of the patients
      but was not associated with the patients' clinical characteristics or their SWS
      and REM sleep patterns. Our results indicate that the commonly reported SWS and
      REM sleep changes in schizophrenia reflect the remnant of prior neuroleptic
      treatment rather than the pathophysiology of the disorder itself.

PMID- 8981389
TI  - The behavioral effect of m-chlorophenylpiperazine (mCPP) and methylphenidate in
      first-episode schizophrenia and normal controls.
AB  - Although there has been renewed interest in the serotonin (5-HT) system in
      schizophrenia, direct evidence for 5-HT dysfunction is limited. This study
      compares the responses of m-chlorophenyl-piperazine (mCPP), a 5-HT agonist, in
      first-episode schizophrenia and a known psychotogenic dopamine agonist,
      methylphenidate. Eighteen patients experiencing their first episode of psychosis
      and eight healthy controls received methylphenidate (0.5 mg/kg) and mCPP (0.1
      mg/kg) intravenously. Behavioral assessments were done before and after the
      procedure, and a peak response to each agent was rated. Methylphenidate, but not
      mCPP, produced psychotic symptoms in patients. mCPP did decrease anxiety,
      hallucinations, and anger and increased agitation, somatic concern, and impaired
      understandability. Both agents had limited effects on controls. In conclusion,
      unlike methylphenidate, mCPP did not produce psychotic symptom activation in
      schizophrenic patients in, and its effects appeared to be nonspecific.

PMID- 8981390
TI  - Beta-adrenoreceptor coupling to GS protein in alcohol dependence, panic disorder,
      and patients with both conditions.
AB  - Ethanol may downregulate G-protein-coupled beta-adrenoreceptors (beta AR). beta
      AR may also be dysregulated in panic disorder (PD). In clinical samples, many
      patients have comorbid alcohol dependence (AD) and PD. Therefore, we investigated
      beta AR coupling in patients with these disorders. We harvested polymorphonuclear
      leukocytes from 24 healthy volunteers (Vs), and from 22 abstinent AD patients, 7
      PD patients, and 9 patients with comorbid AD/PD. beta AR were assayed using
      saturation and agonist-displacement experiments. Group differences were tested
      using one-way analysis of variance (ANOVA). All beta AR binding parameters were
      similar in AD patients and Vs. The ratio of the agonists' dissociation constant
      from the receptor in the low affinity state (KL) to that in the high affinity
      state (KH) was significantly higher in PD patients than in AD patients and Vs
      (930.97 +/- 440.80 vs. 226.2 +/- 94.47 vs. 197.05 +/- 61.03, respectively, p <
      .01). This finding suggests that beta AR are supercoupled to GS in patients with
      PD. There was a trend for higher total receptor density (RT) in AD/PD and PD
      patients (Vs = 39.06 +/- 42.57 vs. AD = 27.93 +/- 23.07 vs. AD/PD = 66.85 +/-
      79.02 vs. PD = 68.36 +/- 49.20, p < .08). There were no differences between AD/PD
      and PD patients, who combined had a significantly higher RT than Vs and AD
      patients (Vs = 38.95 +/- 8.81 vs. AD = 29.63 +/- 5.07 vs. AD/PD = 67.51 +/-
      17.00, fmol/mg protein, p < .04). Finally, AD/PD patients had a significantly
      higher receptor density in the low-affinity conformational state than Vs and AD
      patients, but not PD patients (25.96 +/- 11.59 vs. 10.69 +/- 1.53 vs. 7.62 +/-
      1.08 vs. 17.07 +/- 5.26 fmol/mg protein, respectively, p < .005). beta AR
      function in polymorphonuclear leukocytes is normal in abstinent alcoholics. The
      previously reported abnormal beta AR regulation in alcoholism may be state
      dependent. The higher RT and KL/KH ratio in AD/PD and PD, but not in AD patients,
      suggest that increased beta AR function may be important in the pathophysiology
      of PD.

PMID- 8981391
TI  - Selective sensitization to the psychosis-inducing effects of cocaine: a possible
      marker for addiction relapse vulnerability?
AB  - Patients in inpatient rehabilitation for uncomplicated cocaine dependence were
      asked whether, compared with the time of their first regular use, they could now
      identify changes in the effects of similar doses of cocaine. We asked about a
      spectrum of cocaine effects "then" and "now" and whether the same amount of drug
      caused effects to occur to about the same degree, less intensely (tolerance), or
      more intensely (sensitization). Nearly half our sample developed predominantly
      paranoid psychoses in the context of cocaine use. Sensitization was consistently
      linked only to psychosis-related cocaine effects. It has been proposed that
      mesolimbic dopaminergic sensitization might contribute to addiction severity. A
      preliminary followup of patients who were sensitized or nonsensitized to
      psychosis development suggests that rehospitalization for treatment of addiction
      may be more frequent in the sensitized group.

PMID- 8981392
TI  - Transforming growth factors beta 1 and beta 2 in the cerebrospinal fluid of
      chronic schizophrenic patients.
AB  - Transforming growth factor beta s (TGF beta s) are potent immunosuppressive
      molecules released in the brain after injury. We hypothesized that TGF beta
      levels in cerebrospinal fluid (CSF) of schizophrenic patients would be altered
      because TGF beta can influence neural cell adhesion molecule (N-CAM) expression
      in vitro. The levels of TGF beta 1 and beta 2 in CSF of patients with
      schizophrenia and normal controls measured by ELISA showed no differences. There
      was evidence that the stability of TGF beta in CSF may be altered in
      schizophrenia. For a limited sample, TGF beta 1 and N-CAM concentrations were
      significantly correlated in normal patients (r = 0.98) but not in schizophrenics.
      The results do not support an active neurodegeneration or anti-inflammatory
      response in the central nervous system, which is reflected in the CSF of chronic
      schizophrenics.

PMID- 8981393
TI  - Olanzapine motor side effect.

PMID- 8981394
TI  - Preattentive auditory change detection relies on unitary sensory memory
      representations.
AB  - Event-Related potentials (ERPs) were recorded to series of frequent (standard)
      and three types of rare (deviant) tones differing from the standard in frequency,
      duration, or in both features. All deviants elicited the mismatch negativity
      (MMN) ERP component, indexing the deviation of a sound from the transient
      auditory memory trace of the standard. Duration deviance could be detected only
      after the offset of the duration deviant delaying the MMN to this deviant by 70
      ms compared with the MMN of the frequency deviant. The MMN to the double deviant
      extended only to the latency range of the frequency MMN, revealing that feature
      MMNs were coordinated by a memory trace integrating the outcome of the various
      feature analysers.

PMID- 8981395
TI  - Calbindin-D28K in the nucleus of nerve growth factor-treated PC12 cells.
AB  - Calbindin-D28K (CB) is a calcium-binding protein found within a subset of
      neurons, which has been proposed to buffer intracellular calcium and to protect
      cells from calcium-induced neurodegeneration. The rat pheochromocytoma PC12 cell
      line has been an invaluable tool for studying neuronal development and
      characterizing the molecular actions of nerve growth factor (NGF). Using Western
      and RNAse protection analyses and immunocytochemical and cell fractionation
      techniques, we now report that NGF induces the expression of CB not only in the
      cytoplasm and neurites, but also within the nuclei of PC12 cells. These data
      indicate that PC12 cells can serve as a useful model system in which to study the
      functions of CB and the role of nuclear CB.

PMID- 8981396
TI  - Characterization and expression of presenilin 1 in mouse brain.
AB  - The expression pattern of presenilin 1 (PS-1) in adult mouse brain was
      investigated using antibodies to specific peptides of PS-1. One antibody, Alz14A,
      specifically detected a 53 kDa protein in retinoic acid-treated P19 cells and
      mouse brain protein extracts consistent with the predicted PS-1 molecular weight.
      Immunohistochemical staining revealed that PS-1 was localized predominantly in
      large neurons in areas that were known to be affected by Alzheimer disease (AD)
      such as the hippocampal formation, entorhinal cortex and the subiculum. Selected
      neurons in other regions not known to be directly affected by AD, such as
      thalamic nuclei, Purkinje cells, large neurons in the brainstem and the gray
      matter of the spinal cord, and the dorsal root ganglion, also expressed PS-1.
      These observations suggest that other as yet identified factors might interact
      with mutated presenilins to cause neurodegeneration in AD-affected areas.

PMID- 8981397
TI  - Kainic acid blocks a TTX-sensitive sodium channel in retinal horizontal cells of
      the turtle (Pseudemys scripta elegans).
AB  - The aim of this study was to investigate the effects of excitatory amino acids on
      channels found in horizontal cell membranes using patch-clamp techniques. We
      unexpectedly found that the excitatory amino acid receptor agonist, kainic acid,
      reversibly inhibited the transient tetrodotoxin (TTX)-sensitive Na+ current in
      isolated horizontal cell bodies and axons from the retina of the turtle
      (Pseudemys scripta elegans). The effect of kainic acid was antagonized by the
      glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Kainic acid
      activated a non-selective cation current, a finding that was consistent with
      previous reports, and which would account for the kainate induced depolarisation
      of these cells. The inhibition of the transient TTX-sensitive Na+ current by
      kainic acid might be important in the modification of the kinetics of responses
      to excitatory amino acid analogues often observed during intracellular recording
      from these cells.

PMID- 8981398
TI  - Prenatal lesioning of vestibular organ by aminoglycosides.
AB  - The effects of gentamicin administrated to gravid mice on the vestibular hair
      cells of their offspring were investigated. Scanning electron microscopy showed
      the effect to be dose-dependent and age-dependent, and there was a different
      sensitivity to toxicity for each of the three types of vestibular receptors. The
      destructive action of gentamicin on the vestibule before birth provides a
      mechanism to study the influence of the vestibular system on the central nervous
      system throughout its development.

PMID- 8981399
TI  - Brain processing of native and foreign languages.
AB  - We used positron emission tomography to study brain activity in adults while they
      were listening to stories in their native language, in a second language acquired
      after the age of seven, and in a third unknown language. Several areas, similar
      to those previously observed in monolinguals, were activated by the native but
      not by the second language. Both the second and the unknown language yielded
      distinct left-hemispheric activations in areas specialized for phonological
      processing, which were not engaged by a backward speech control task. These
      results indicate that some brain areas are shaped by early exposure to the
      maternal language, and are not necessarily activated by the processing of a
      second language to which they have been exposed for a limited time later in life.

PMID- 8981400
TI  - IL-1 beta, IL-1 receptor type I and iNOS gene expression in rat brain vasculature
      and perivascular areas.
AB  - The mechanism by which IL-1 beta exerts its actions in the brain during systemic
      inflammation is not fully understood, as neither IL-1 receptor gene expression
      nor IL-1 binding have been identified in significant levels in key areas that
      respond to IL-1 beta. Having hypothesized that perivascular nitric oxide (NO)
      might modulate the effects of systemic IL-1 beta in the brain, we studied the
      expression of the genes encoding for IL-1 beta, the signal-transducing IL-1
      receptor type I (IL-1RI) and inducible NO synthase (iNOS) constitutively and
      during systemic inflammation in vascular and perivascular regions of the rat
      brain. Our results show that IL-1RI is constitutively expressed at the interface
      of the vascular wall and perivascular glia. During systemic inflammation there is
      induction of IL-1 beta gene expression in the vascular wall, accompanied by
      perivascular induction of iNOS mRNA. We conclude that during systemic
      inflammation vascular IL-1 beta, binding to vascular and perivascular IL-1RI
      receptors, may induce perivascular iNOS gene expression, leading to the
      production of NO and modulation of the effects of IL-1 beta in the brain. We
      propose that the vascular and peri-vascular induction of iNOS mRNA by IL-1 beta
      might represent a mechanism for the modulation of the central nervous system
      effects of peripheral inflammatory mediators.

PMID- 8981401
TI  - Are there cholinergic and non-cholinergic paradoxical sleep-on neurones in the
      pons?
AB  - Using microiontophoresis on unanesthetized head-restrained cats, we have found
      two distinct groups of neurones exhibiting tonic discharge specific to
      paradoxical sleep (PS) (PS-on neurones) in the mesopontine tegmentum, which
      contains both cholinergic and non-cholinergic neurones. One group is
      characterized by a broad action potential, slow conduction velocity and an
      inhibitory response to a potent cholinergic agonist, carbachol, applied
      iontophoretically during PS. The other is characterized by a short action
      potential, fast conduction velocity and an excitatory response to applied
      carbachol. All PS-on neurones were excited by glutamate. The present findings
      demonstrate the existence of two types of PS-on neurones and suggest their
      cholinergic and noncholinergic neurochemical properties.

PMID- 8981402
TI  - Reduced survival of apolipoprotein E4 homozygotes in Down's syndrome?
AB  - An increased frequency of apolipoprotein E (ApoE) allele epsilon 4 has been
      established in Alzheimer's disease (AD) subjects. Based on the observation that
      all individuals with Down's syndrome (DS) develop the neuropathology of AD by the
      age of 40 years we sought to determine whether ApoE genotype affected the
      clinical symptoms of AD. Unexpectedly, we failed to find any epsilon 4
      homozygotes, as have other published studies: this is highly significant
      statistically. We suggest this is due to decreased survival or, less likely,
      embryonic lethality of epsilon 4 homozygotes in DS.

PMID- 8981404
TI  - Developmental changes in arachidonic acid potentiation of NMDA currents in
      cortical neurones.
AB  - Developmental changes in the effects of arachidonic acid (AA) on N-methyl-D
      aspartate (NMDA) receptor-mediated currents were investigated in acutely
      dissociated rat cortical neurones using a whole-cell patch-clamp method. AA
      potentiated peak NMDA currents (INMDA) in a concentration-dependent manner.
      Potentiation by AA was greater at 2-4 postnatal days (P2-4) than at P7-8 and P15
      18. Indomethacin reduced the potentiating effect of AA only at P2-4, while
      caffeic acid and baicalein showed no apparent effect, indicating that metabolites
      of the cyclooxygenase pathway contribute to INMDA potentiation at P2-4.
      Staurosporine diminished the potentiation of INMDA at P2-4, suggesting that
      protein kinase C might participate in the effect of AA. These findings suggest
      that the greater potentiation of INMDA by AA at P2-4 has a different underlying
      mechanism from effects seen at P7-8 or older.

PMID- 8981403
TI  - Chronic L-dopa alters striatal NMDA receptors in rats with dopaminergic injury.
AB  - To examine the effects of chronic L-dopa treatment on excitatory amino acid
      receptors, rats with unilateral nigrostriatal injury and intact controls were
      treated for 21 days with Sinemet (L-dopa+carbidopa) or vehicle followed by a 3
      day washout period. Nigrostriatal damage induced by unilateral injection of 6
      hydroxy-dopamine (6-OHDA) produced an extensive decline in [3H]mazindol binding
      in the ipsilateral caudate-putamen (CPu) and a small (7%) decline in
      [3H]glutamate binding to N-methyl-D-aspartate (NMDA) receptors in CPu. Sinemet
      treatment of 6-OHDA-injected rats further reduced the binding of [3H]glutamate to
      NMDA receptors. The greatest reductions (-34%) occurred in the denervated CPu,
      but moderate declines (-18% to -22%) were also observed in the CPu, nucleus
      accumbens and cingulate cortex of the intact hemisphere. Unexpectedly, chronic
      Sinemet treatment also caused a decrease in [3H]mazindol binding in both
      hemispheres of rats receiving unilateral 6-OHDA injections. L-Dopa/ carbidopa
      treatment did not affect [3H]glutamate or [3H]mazindol binding in neurologically
      intact rats.

PMID- 8981405
TI  - Developmental changes in the distribution of oestrogen receptor mRNA expressing
      cells in the forebrain of female, male and masculinized female zebra finches.
AB  - In female zebra finches, oestrogens induce a male-like development of forebrain
      song nuclei such as the hyperstriatalis ventrale, pars caudal (HVC) and robustus
      archistriatalis (RA) that are normally highly sexually dimorphic. The
      distribution of oestrogen receptor (ER) mRNA in the vocal control system of male,
      female and oestrogen-treated female zebra finches was assessed between the day of
      hatching and adulthood using in situ hybridizations with a zebra finch-specific
      ER probe. ER mRNA was first expressed in the caudal forebrain at posthatching (P)
      day P5 to P7. At this age, ER mRNA-expressing cells lined the lateral ventricle.
      This band of labelling extended into the medial portion of HVC from P15 onwards.
      ER mRNA was found in the shell of the RA from P20 onwards. ER were not expressed
      in other vocal control areas at any age. Thus oestrogens seem to induce ER
      mediated differentiation of the vocal control system via action in the medial
      HVC, in the area along the lateral ventricle and in the shell of the RA. This
      differentiation does not involve oestrogen-induced upregulation of ER in vocal
      control areas. Since the distribution of ER mRNA in the caudal forebrain was
      similar in juvenile males and females, ER pattern does not explain the sex
      specific differentiation of the song system.

PMID- 8981406
TI  - Injection of a GABA antagonist into the mesopontine reticular formation abolishes
      haloperidol-induced catalepsy in rats.
AB  - THE pedunculopontine nucleus and its adjacent structure of the mesopontine
      reticular formation are known as a mesencephalic locomotor region, since either
      electrical or chemical stimulation of these regions induces locomotion in
      decerebrate animals. In parkinsonism, it is presumed that the pedunculopontine
      nucleus is under GABAergic overinhibition from the basal ganglia. To reveal the
      behavioural effects of GABAergic disinhibition of the mesopontine reticular
      formation in parkinsonism, picrotoxin, a GABAA antagonist, (5 or 10 ng/ 0.25
      microliter) or vehicle was injected unilaterally into the mesopontine reticular
      formation of rats via implanted cannulae after induction of catalepsy using
      haloperidol (1.5 mg kg-1, i.p.). Injection of the larger dose of picrotoxin, but
      not the smaller dose nor the vehicle, abolished the catalepsy with or without
      spontaneous locomotor activity. The present result suggests that the
      disinhibition of the brainstem output structures contributes to the recovery of
      mobility in the cataleptic state induced by blocking the dopaminergic
      transmission of the basal ganglia.

PMID- 8981407
TI  - Optimal resource allocation for novelty detection in a human auditory memory.
AB  - A theory of resource allocation for neuronal low-level filtering is presented,
      based on an analysis of optimal resource allocation in simple environments. A
      quantitative prediction of the theory was verified in measurements of the
      magnetic mismatch response (MMR), an auditory event-related magnetic response of
      the human brain. The amplitude of the MMR was found to be directly proportional
      to the information conveyed by the stimulus. To the extent that the amplitude of
      the MMR can be used to measure resource usage by the auditory cortex, this
      finding supports our theory that, at least for early auditory processing, energy
      resources are used in proportion to the information content of incoming stimulus
      flow.

PMID- 8981408
TI  - Attention deficits in depression: an electrophysiological marker.
AB  - EVENT-RELATED POTENTIALS were recorded in young depressed subjects and compared
      with results from controls. Subjects were required to respond to targets (rare
      high-frequency sounds) presented to a designated ear, and to ignore targets
      presented to the non-designated ear as well as standards (frequent low-frequency
      sounds) presented to either ear. The results confirm those previously obtained
      with elderly depressed patients, showing the same general profile of
      electrophysiological and behavioural differences, and in particular a substantial
      reduction of the N200 amplitude in response to attended targets in depressed
      subjects. It is suggested that the N200 component could be a marker of
      depression.

PMID- 8981409
TI  - Cholesterol protects PC12 cells from beta-amyloid induced calcium disordering and
      cytotoxicity.
AB  - THE neurotoxic action of beta-amyloid seems to play an important role in the
      pathogenesis of Alzheimer's disease. The disruption of calcium homeostasis by
      beta-amyloid has been suspected to be the mechanism of its neurotoxicity. We
      found that beta-amyloid 25-35 induces a rapid increase in cytosolic calcium of
      PC12 cells, and subsequently, a dramatic decrease in cell viability. The increase
      in cytosolic calcium induced by beta-amyloid is effectively blocked by
      cholesterol in a dose-dependent manner. Furthermore, pretreatment of PC12 cells
      with cholesterol also significantly attenuates the neurotoxicity induced by beta
      amyloid. These findings suggest that extracellular free cholesterol can protect
      neurones from beta-amyloid neurotoxicity mediated by the disruption of calcium
      homeostasis.

PMID- 8981410
TI  - Co-alteration of dopamine D2 receptor and muscarinic acetylcholine receptor
      binding in rat striatum after circling training.
AB  - CIRCLING training (CT) decreases muscarinic acetyl-choline receptor (mAchR)
      binding in rat striatum. As cholinergic and dopaminergic systems interact
      strongly we evaluated the expression of D2-subtype dopamine receptor (DA D2) and
      mAchR together after CT. Animals trained from 30 to 37 days of age and sacrificed
      2 months later showed an enduring drop in Bmax of 40% in DA D2 and 34% in mAchR.
      Plotting the percentage of binding drop of both receptors for each animal showed
      that the reduction of one system correlates with the other (r2 = 0.71, p < 0.01;
      n = 8). Neither mAchR nor DA D2 were affected when training started at 20 or 60
      days. We conclude that the presence of a period where CT exerts long term
      alterations during development involves both cholinergic and dopaminergic
      systems.

PMID- 8981411
TI  - NT-3 has a tropic effect on process outgrowth by postnatal auditory neurones in
      vitro.
AB  - CONFOCAL analysis of early postnatal auditory neurones in a bicompartmental
      culture system was used to test for chemoattractant properties of NGF, BDNF and
      NT-3 on neuronal process outgrowth. NT-3 exerted a strong tropic effect on
      neuritic outgrowth from auditory neurones in this system. BDNF and NGF did not
      have any tropic activity that directed processes outgrowth from auditory
      neurones. However, BDNF was important for the support of neuronal survival in NGF
      treated cultures and for neuritogenesis in NT-3-treated cultures. Since NT-3 has
      been identified as both a survival factor and a chemotropic agent for auditory
      neurones, it is likely that this neurotrophin will be a useful therapeutic agent
      in the treatment of damaged cochleae for the recovery of hearing.

PMID- 8981412
TI  - Hypothalamic growth hormone-releasing hormone mRNA varies across the day in rats.
AB  - Experiments were performed to determine whether growth hormone-releasing hormone
      (GHRH) mRNA displays diurnal variations in the hypothalamus and cortex of the
      rat. Levels of GHRH and beta-actin mRNA were measured from hypothalamic and
      cortical extracts using the reverse transcriptase polymerase chain reaction
      method in rats sacrificed at 4 h intervals across a 12:12 h light:dark cycle.
      Hypothalamic GHRH mRNA peaked around the light onset, declined during the light
      period, and stayed low in the dark. Variations in hypothalamic beta-actin and
      cortical GHRH mRNA levels were not observed. beta-Actin mRNA expression in the
      cortex was higher in the dark than in the light period. The results demonstrate
      that hypothalamic GHRH mRNA displays diurnal variations.

PMID- 8981413
TI  - Analysis of AMPA receptor subunit mRNA expression in control and ALS spinal cord.
AB  - The distribution of glutamate receptor subunits in human spinal cord has yet to
      be fully elucidated. The aim of this study was to examine the distribution of
      mRNAs for the subunits of the AMPA type of glutamate receptor (GluR A, B, C and
      D) in control human spinal cord using in situ hybridization and to examine in
      parallel the expression of these mRNAs in patients with sporadic amyotrophic
      lateral sclerosis (ALS). We also quantitated mRNA levels for these subunits in
      spinal cord homogenates. The relative abundances of the receptor subunits were as
      follows: GluR A > GluR B > GluR D > GluR C with A, B and D expressed in foci
      corresponding to the medial, lateral and ventral clusters of motor neurones.
      Quantitation of homogenates revealed a significant decrease (38%) in GluR A mRNA
      in ALS spinal cord compared with controls, and a 67% decrease of GluR B mRNA
      compared with controls. Levels of GluR C and D were too low to analyse
      densitometrically.

PMID- 8981414
TI  - Sulphonylureas reverse hypoxia induced K(+)-conductance increase in substantia
      nigra pars reticulata neurones.
AB  - Membrane potentials were recorded from neuronal somata in the substantia nigra
      pars reticulata of the rat midbrain slice using the whole-cell patch-clamp
      technique. Hypoxia induced a consistent decrease in input resistance often
      accompanied by membrane hyperpolarization and cessation of firing. The membrane
      hyperpolarization was mediated by K+ as indicated by its reversal potential at 
      88 +/- 9 mV, which is close to the equilibrium potential of K+. The hypoxic
      response was not sensitive to 1 microM tetrodotoxin or superfusion with Ca2(+)
      free medium. While glibenclamide at 30 microM and tolbutamide at 300 microM had
      no effect on the resting membrane properties of the neurones, these
      sulphonylureas reversed the hypoxia-induced membrane hyperpolarization and
      restored firing. Inclusion of 2 mM of ATP in the recording pipette also prevented
      the hyperpolarization. These observations suggest that post-synaptic ATP
      sensitive potassium channels exist on the GABA neurones of SNR and that these
      channels are activated in energy-depleting conditions exemplified by hypoxia.

PMID- 8981415
TI  - Rapid uncoupling of oxidative phosphorylation accompanies glutamate toxicity in
      rat cerebellar granule cells.
AB  - A 100 microM glutamate pulse administered to rat cerebellar granule cells causes
      a very rapid and progressive decrease in both cell and mitochondrial oxygen
      consumption caused by glucose and succinate addition, respectively. The
      respiratory control ratio, which reflects the ability of mitochondria to produce
      ATP, is reduced by 50% within the first 30 min after glutamate addition.
      Subsequent to glutamate exposure, a progressive decrease of respiratory control
      ratio to almost 1 was found within the following 3-5 h. The addition of extra
      calcium had no effect per se on oxygen consumption by cell homogenate.

PMID- 8981416
TI  - The CaM-kinase II inhibitor KN-62 blocks NMDA but not kainate stimulation of NO
      synthesis.
AB  - We have studied the effect of CaM-kinase II inhibition induced by KN-62 on NO
      synthesis mediated by the activation of NMDA and kainate receptors in striatal
      neurones. KN-62 partially inhibited NMDA-mediated NO synthesis but the effect of
      kainate on NO production was unaffected by the specific CaM-kinase II inhibitor.
      Ionomycin-induced cGMP production and the NMDA-mediated superoxide generation by
      nNOS were also inhibited by KN-62. Since we determined the NO synthesis via its
      ability to increase intracellular cGMP, we checked that the kinase inhibitor was
      unable to block the cGMP production induced by a NO-donor like 3
      morpholinosydnonimine (SIN-1). In conclusion, these results indicate that,
      depending on the glutamatergic receptors involved, CaM-kinase II could
      participate in the regulation of NO synthesis in striatal neurones.

PMID- 8981417
TI  - A thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific
      neurotoxicity.
AB  - A 22 kDa fragment of apoE containing a putative cytotoxi domain was identified in
      postmortem human brain tissue and fresh CSF. This fragment is apparently
      equivalent to the major apoE thrombin cleavage product. In vitro toxicity assays
      demonstrate that the corresponding fragment derived from recombinantly expressed
      human apoE is toxic to primary neurons in culture and that the E4-derived
      fragment is significantly more toxic than the fragment derived from the E3
      isoform. These results suggest that proteolytic fragments of apoE may play a
      direct role in the pathology associated with AD and other diseases in which apoE
      has been implicated.

PMID- 8981418
TI  - Rat astroglial P2Z (P2X7) receptors regulate intracellular calcium and purine
      release.
AB  - Treatment of rat astrocyte cultures with 2'- and 3'-O-(4-benzoylbenzoyl)
      adenosine 5'-triphosphate (BzATP), a P2X7 agonist, but not with adenosine 5
      [alpha, beta methylene] triphosphate (alpha, beta meATP), a P2X agonist,
      increased influx of extracellular Ca2+ and [Ca2+]i. Lucifer yellow, a small
      molecule which permeates P2X7 receptor-induced pores, entered BzATP-treated but
      not control astrocytes. BzATP also stimulated efflux of [3H]purine from cultured
      astrocytes. The P2X7 receptor antagonist oxidized ATP abolished the effects of
      BzATP on [Ca2+]i, lucifer yellow permeation and [3H]purine release, indicating
      that these effects were due to P2X7 receptor activation. In neurological diseases
      or injuries extracellular ATP may activate P2X7 receptors further enhancing
      [3H]purine release, with important pathophysiological consequences.

PMID- 8981419
TI  - Cycloheximide inhibits kainic acid-induced GAP-43 mRNA in dentate granule cells
      in rats.
AB  - We have previously shown that kainic acid-induced seizures in adult rats caused
      an up-regulation of GAP-43 mRNA in the granule cells of the hippocampus,
      suggesting an involvement of this protein in the kainic acid-induced sprouting of
      mossy fibres. To determine whether this effect was dependent on the synthesis of
      proteins activated under these experimental conditions we examined the effect of
      cycloheximide, a protein synthesis inhibitor, on kainic acid-induced GAP-43 mRNA.
      Cycloheximide, injected s.c. 2 h but not 8 h after kainic acid, markedly reduced
      the increased expression of GAP-43 mRNA in granule cells. These results suggest
      that a rapid mechanism involving new protein synthesis is activated by kainic
      acid to induce GAP-43 in the granule cells and possibly trigger the structural
      remodeling of mossy fibres.

PMID- 8981420
TI  - YM-50001: a novel, potent and selective dopamine D4 receptor antagonist.
AB  - We investigated some in vitro pharmacological properties of a novel human
      dopamine D2-like receptor antagonist, YM-50001 [(R)-5-chloro-4
      cyclopropylacarbonylamino-2-methoxy-N-[1-(3-methox ybenzyl)- 3
      pyrrolidinyl]benzamide monooxalate]. Receptor binding studies revealed that YM
      50001 had a potent affinity for human D4 receptors (Ki = 5.62 nM). YM-50001
      displayed weak or negligible affinity for other neurotransmitter receptors
      including human D2 and D3 receptors. YM-50001 shifted the dopamine response curve
      on each human D2-like receptor subtype-mediated low-Km GTPase activity to the
      right. YM-50001 also exhibited good D4 selectivity with respect to D2-like
      receptor antagonism in the functional assay. These results indicate that YM-50001
      is a novel, potent and selective D4 receptor antagonist.

PMID- 8981421
TI  - GDNF enhances dopaminergic cell survival and fibre outgrowth in embryonic nigral
      grafts.
AB  - Two groups of rats with unilateral 6OHDA lesions received either intrastriatal
      suspension grafts of embryonic ventral mesencephalon or sham grafts. Three
      subgroups of each of these received intrastriatal infusions of 1000 ng or 500 ng
      glial cell-line derived trophic factor (GDNF) or vehicle alone for 10 consecutive
      days. There was a highly significant dose-dependent effect of GDNF both on the
      number of TH-positive cells surviving in the grafts and on the density of fibre
      outgrowth. All grafted rats showed rapid compensation of amphetamine-induced
      rotation compared with rats with sham grafts. GDNF may provide a powerful tool to
      enhance the survival and maturation of dopaminergic neurones within mesencephalic
      transplants.

PMID- 8981422
TI  - Role of GABAA receptors in the organization of brain and behavioural sex
      differences.
AB  - Sex differences in GABA neurotransmitter have been described. We have studied the
      involvement of the GABAA receptor in sex differences in the brain and
      reproductive behaviour. Neonatal administration of the GABAA agonist diazepam to
      male rats facilitated the induction of maternal behaviour in adults, while the
      antagonist picrotoxin disrupted it in females. Sex differences in the accessory
      olfactory bulb were also reversed, but gonadal function remained unaltered in
      both sexes. This suggests that neonatal changes in neuronal membrane permeability
      to Cl- ions may play a role in the organization of sex differences. Our study
      constitutes a new model for understanding the early neurobiological organization
      of sex differences.

PMID- 8981423
TI  - Ionizing radiation induces expression of immediate early genes in the rat brain.
AB  - In situ hybridization histochemistry and immunocytochemistry were used to examine
      whether therapeutic ionizing radiation induces expression of immediate early
      genes in the rat brain. One hour following a single dose of 2 or 15 Gy the
      expression of c-fos and zif-268 but not of c-jun mRNAs was induced in a scattered
      cell population in the lateral striatum, whereas in the piriform cortex the
      expression of zif-268 mRNA was decreased. Other brain regions did not show
      consistent changes in the mRNA levels. Three hours after radiation the mRNA
      levels had returned to normal. Immunocytochemistry showed the number of c-Fos and
      Jun-B-positive neurones to be increased in the striatum and slightly increased in
      the frontoparietal cortex 1 and 3 h after radiation. The results show that a
      subpopulation of neurones is sensitive to ionizing radiation at the clinically
      relevant dose of 2 Gy and that the neuronal response to this irradiation involves
      altered expression of genes encoding for transcription factors.

PMID- 8981424
TI  - GLAST mRNA expression in the periventricular area of experimental hydrocephalus.
AB  - Glutamate transporters play an important role in maintaining the extracellular
      glutamate concentration below the neurotoxic level. We investigated the
      expression of glutamate/aspartate transporter (GLAST) mRNA in the periventricular
      region of rats with kaolin-induced hydrocephalus by in situ hybridization (ISH).
      The density of GLAST mRNA-positive cells and the level of hybridization signals
      per positive cell significantly increased in the acute stage of hydrocephalus. We
      also demonstrated co-localization of GLAST mRNA and GFAP immunoreactivity in a
      single cell using the combined methods of ISH and immunohistochemistry. These
      findings suggest that GLAST is expressed in the reactive astrocytes of the
      periventricular area and regulates extracellular glutamate concentration after
      hydrocephalic brain injury.

PMID- 8981425
TI  - Nitrergic cerebral vasodilatation provoked by the periaqueductal grey.
AB  - The present study evaluated the contribution of nitric oxide to the increase in
      cerebral cortical blood flow that is provoked by chemical stimulation of the
      caudal third of the lateral periaqueductal grey (PAG), employing 48 anaesthetized
      rats with cervical cordotomy. Following topical application over the cortical
      surface, the inhibitor of nitric oxide synthase NG-nitro-L-arginine inhibited the
      response stereospecifically and achieved its maximal effect at 1 mM, when the
      response was reduced to 47 +/- 16% (n = 16). Since the PAG represents a principal
      site for the central organization of defence reactions, we suggest that nitric
      oxide may play a definitive role in the central regulation of the cerebral
      circulation, thereby participating in such important biological processes as the
      defensive reflex activity.

PMID- 8981426
TI  - A novel K+ channel blocker isolated from 'hiccup nut' toxin.
AB  - Combretastatin B1, a polyhydroxybibenzyl compound extracted from the fruit of
      Combretum kraussii, known to contain 'hiccup nut' toxin, reversibly increased the
      duration, but not the peak or the rate of rise, of the action potential in rat
      sensory neurones by approximately 300%. This effect was only seen when it was
      applied to the extracellular side of the membrane. No effects on the resting
      potential were observed. K+ delayed rectifier currents were inhibited in neurones
      and in human myotubes with an IC50 of about 300 microM; the HERG-type inward
      rectifier channels in tumour cells were inhibited to a greater degree. Due to its
      selective action and the similarity of its blockade to that produced by class III
      antiarrhythmic drugs, the toxin could be the origin of compounds of potentially
      significant pharmacological interest.

PMID- 8981427
TI  - Ultrastructural localization of glutamate receptor subunits (NMDAR1, AMPA GluR1
      and GluR2/3) and spinothalamic tract cells.
AB  - The associations of glutamate receptor subunits (NMDAR1, AMPA GluR1 and GluR2/3)
      and spinothalamic tract neurons in the rat lumbar spinal cord dorsal horn were
      investigated. Staining for NMDAR1 and AMPA GluR1 and GluR2/3 receptor subunits
      was observed throughout the spinothalamic tract soma and dendrites, particularly
      in association with the rough endoplasmic reticulum and some postsynaptic
      membrane sites. Immunostaining for NMDAR1 and AMPA GluR2/3 was also noted in
      presynaptic membrane sites. Localization of both NMDA and AMPA glutamate receptor
      subunits in association with spinothalamic tract neurons provides anatomical
      evidence in support of the various interactions reported for glutamate receptors
      in nociception. Presynaptic localization of the AMPA GluR2/3 receptor subunit
      suggests that spinothalamic tract cells may also be affected presynaptically by
      AMPA glutamate receptor interactions.

PMID- 8981428
TI  - Localization of presenilin-1 mRNA in rat brain.
AB  - We examined the regional and cellular distribution of presenilin-1 gene
      expression in the rat brain by in situ hybridization. Microscopic analysis
      demonstrated that presenilin-1 mRNA is predominantly expressed in areas such as
      the occipital cortex, the pyramidal layer of the hippocampus, thalamic nuclei and
      the cerebellar granular layer. The expression of presenilin-1 is mostly neuronal:
      only a weak hybridization signal was found in the corpus callosum and in the
      astrocytoma cell lines U373MG and U138MG.

PMID- 8981429
TI  - Apoptosis occurs independently of the release of interleukin-1 beta in the
      anterior pituitary of end-lactating rats.
AB  - The mechanism of Interleukin-1 beta (IL-1 beta) release remains unknown. Because
      of the absence of typical peptide signal on the precursor, IL-1 beta is not
      secreted through the classical pathway. The aim of this study was to determine
      whether IL-1 beta is released during apoptosis, as has been reported for
      activated macrophages. We chose anterior pituitary cells of end-lactating rats
      because of their capacity to produce IL-1 beta spontaneously and because this
      organ undergoes cellular degeneration. The combination of two techniques, reverse
      haemolytic plaque assay (RHPA) and terminal transferase dUTP nick end labelling
      (TUNEL), allowed us to observe simultaneously the release of IL-1 beta and
      apoptosis. Our results show that in these conditions apoptosis is not the
      mechanism of IL-1 beta release.

PMID- 8981430
TI  - A simulated actuator driven by motor cortical signals.
AB  - One problem in motor control concerns the mechanism whereby the central nervous
      system translates the motor cortical command encoded in cell activity into a
      coordinated contraction of limb muscles to generate a desired motor output. This
      problem is closely related to the design of adaptive systems that transform
      neuronal signals chronically recorded from the motor cortex into the
      physiologically appropriate motor output of multijoint prosthetic limbs. In this
      study we demonstrated how this transformation can be carried out by an artificial
      neural network using as command signals the actual impulse activity obtained from
      recordings in the motor cortex of monkeys during the performance of a task that
      required the exertion of force in different directions. The network receives
      experimentally measured brain signals and recodes them into motor actions of a
      simulated actuator that mimics the primate arm. The actuator responds to the
      motor cortical commands with surprising fidelity, generating forces in close
      quantitative agreement with those exerted by trained monkeys, in both the
      temporal and spatial domains. Moreover, we show that the time-varying motor
      output may be controlled by the impulse activity of as few as 15 motor cortical
      cells. These results outline a potentially implementable computation scheme that
      utilizes raw neuronal signals to drive artificial mechanical systems.

PMID- 8981431
TI  - Visualization of lCBF changes during cortical infarction using IR thermo
      encephaloscopy.
AB  - Infrared thermo-encephaloscopy (IR-TE) was used for two-dimensional imaging of
      local cortical blood flow (lCBF) with high spatio-temporal resolution. The basis
      of this method is the transfer of thermal energy from circulating blood to
      cortical tissue depending on local perfusion. Temperature fields that emerge from
      differences in lCBF can be measured with a high resolution thermo-scanner.
      Infarctions 2 mm in diameter were produced by photochemically induced thrombosis
      and IR-TE was used to visualize lCBF changes in and around the focal infarction.
      The infarcted region was characterized by a lower temperature (0.1-0.3 K) than
      that of the surrounding tissue. In addition to the visualization of persistent
      blood flow changes it was possible to detect dynamic lCBF changes that might
      correlate with long-lasting hyperaemia and episodes of cortical spreading
      depression (SD).

PMID- 8981432
TI  - Intra-arterial infusion of [125I]A beta 1-40 labels amyloid deposits in the aged
      primate brain in vivo.
AB  - Alzheimer's disease is characterized by extracellular amyloid deposits in the
      brain at both vascular sites (cerebrovascular amyloid, CVA) and within the
      neuropil (plaques). In the present study we demonstrated that brain amyloid of
      aged non-human primates is efficiently detected by [125I]A beta in vitro, and
      assessed the detection of that amyloid in vivo by intravascular infusion of
      [125I]A beta. Aged squirrel monkeys (Saimiri sciureus) were anesthetized and
      infused intra-arterially with [125I]A beta, and sacrificed 2 h later. Analysis of
      the anterior frontal and temporal cortices by autoradiography demonstrated that
      [125I]A beta was deposited on CVA and that essentially every amyloid deposit
      which could be detected with thioflavin S or anti-A beta antibodies was also
      labeled by [125I]A beta. These experiments suggest that intravascular infusion of
      radiolabeled A beta can be used to detect and image amyloid deposits in the human
      AD brain.

PMID- 8981433
TI  - Non-NMDA receptor-mediated modulation of voltage-activated outward currents in
      chick neurones.
AB  - The effect of kainate on the voltage-activated current of cultured embryonic
      chick telencephalic neurones was studied by whole-cell voltage clamp recording.
      In addition to opening non-NMDA receptor coupled ion channels, kainate produced
      additional effects, with a slower time course: it modulated voltage-activated
      currents. These effects were blocked by the non-NMDA receptor antagonists CNQX (6
      cyano-7-nitroquinoxaline-2,3-dione) and GYKI 53784 ((-)-1-(4-aminophenyl)-3-
      methylcarbamoyl-4-methyl-7,8-methylenedioxy-3,4- dihydro-5H-2,3-benzodiazepine),
      indicating that non NMDA receptors are involved. It has been shown that the
      reversible inhibition of outward potassium currents was partly due to a decrease
      of current amplitude and partly to a marked shift of the inactivation curve
      towards more negative potentials.

PMID- 8981434
TI  - Photochemically induced ischaemic lesion of the rat sciatic nerve. A novel method
      providing high incidence of mononeuropathy.
AB  - The incidence of behavioural signs of mononeuropathy in rats subjected to chronic
      constriction injury (CCI) of the sciatic nerve is unpredictable and often low. In
      the present study, an ischaemic lesion of the rat sciatic nerve was induced
      photochemically using a low power laser. In these rats tactile allodynia
      developed with a considerably greater incidence (95%) than in control rats
      subjected to CCI (45%). The allodynia lasted longer and was more prominent.
      Responses to thermal stimulation did not markedly differ between the two groups.
      The ischaemic lesions displayed marked degeneration, particularly of large
      myelinated fibres. The results suggest that laser irradiation of a peripheral
      nerve inducing a local photochemical reaction followed by Wallerian degeneration
      may be a convenient and reproducible experimental method of producing signs of
      peripheral mononeuropathy.

PMID- 8981435
TI  - Memory dysfunction of the frontal type in normal ageing.
AB  - In this study healthy subjects divided into five consecutive age groups (20-60
      years of age) completed a series of memory tasks which had previously been shown
      to reveal impairments in patients with frontal lobe lesions. Significant age
      differences were found for free recall, retention rates for material which
      required effortful encoding, memory for temporal order and prospective memory. In
      the tests addressing these memory functions, subjects of more than 60 years of
      age performed more poorly than the youngest group, and they also showed evidence
      of false recognition (increased false alarm rates and confabulatory responses).
      The general pattern suggests that inefficient frontal functioning might
      contribute to age-related memory problems.

PMID- 8981436
TI  - Reaching movements: programming time course is independent of choice number.
AB  - The present study was undertaken to assess the effect of varying the number of
      choices on the time needed by human subjects to program the correct direction of
      reaching arm movements. Subjects were required to reach for visual targets
      presented in two, four or eight different directions. In none of these subjects
      was the time needed to program response direction correctly prolonged by
      increasing the number of choices. In the present experimental situation, the time
      course of the process by which information derived from a visual target is used
      to accurately set the direction of reaching arm movements is uninfluenced by the
      number of possible targets.

PMID- 8981437
TI  - Localization of leptin receptor mRNA expression in mouse brain.
AB  - The distribution of the leptin receptor in the brain of C57 mice was investigated
      using a non-radioactive in situ hybridization method. Leptin receptor mRNA
      expression was highest in the arcuate nucleus and median eminence of the
      hypothalamus, but it was also abundant in hippocampus, primarily in the dentate
      gyrus and CA1, and was detected at low levels in piriform cortex and the medial
      margin of the medial habenular nucleus. The localization of leptin receptor
      containing neurones in the present study indicates the possibility that the
      leptin receptor is expressed on neuropeptide Y-containing neurones.

PMID- 8981438
TI  - NGF attenuates 3-nitrotyrosine formation in a 3-NP model of Huntington's disease.
AB  - Nerve growth factor (NGF)-secreting fibroblasts are able to protect against the
      Huntington-like striatal neurodegeneration induced by the mitochondrial toxin 3
      nitropropionic acid (3-NP). In the present study, we investigated whether the
      neuroprotective effects of NGF are mediated through antioxidative mechanisms.
      Rats were grafted in the corpus callosum with NGF[+] or NGF[-] fibroblasts 7 days
      before administration of 3-NP. The generation of peroxynitrite was evaluated by
      measuring the striatal levels of 3-nitrotyrosine. NGF significantly decreased the
      3-NP induced generation of 3-nitrotyrosine, presumably by decreasing
      peroxynitrite formation. These findings suggest that NGF might protect against
      neuronal death by inhibiting the production of nitric oxide or decreasing the
      levels of superoxide radicals, thereby decreasing the generation of oxidative
      agents such as peroxynitrite.

PMID- 8981439
TI  - Optical and FDG mapping of frequency-specific activity in auditory cortex.
AB  - With optical recording of intrinsic signals (ORIS) and tone stimulation, we
      analysed frequency- and intensity-dependent spatio-temporal activity in primary
      auditory cortex AE of awake Mongolian gerbils. We found a two-dimensional and
      assymetric propagation of ORIS activity (1) from ventral to dorsal along
      isofrequency contours at all frequencies and (2) from the low-frequency end
      across the complete tonotopic gradient at low frequencies. High-frequency
      representations remained tonotopic. Tonotopic asymmetries were independent of
      stimulus intensity. By contrast, in fluoro-2-deoxyglucose images from the same
      animals metabolic activity was tonotopically confined at high and low
      frequencies. The assymetric tonotopic propagation of ORIS activity suggests
      subthreshold directional interaction mechanisms in the cortical network which may
      serve to relate low- to high-frequency components of complex sounds.

PMID- 8981440
TI  - Ulcerogenic cinchophen induces c-Fos expression in CRH-secreting cells in the PVH
      of rat brain.
AB  - This study aimed at obtaining evidence that cinchophen, an ulcerogenic drug,
      stimulates the corticotropin-releasing hormone (CRH)-secreting cells in the
      paraventricular nucleus of the hypothalamus (PVH) to induce c-Fos expression.
      Without colchicine pretreatment, cinchophen was injected i.p. 60 min before the
      time of maximum CRH level in the hypothalamus, as decided by radioimmunoassay.
      Eighty percent of the c-Fos/CRH double-labelled cells were concentrated in the
      parvicellular subnuclei. In the medial and anterior parvicellular subnuclei, the
      double-labelled neurones of treated rats significantly outnumbered those of
      controls. The result shows that cinchophen induces excitation of the CRH
      secreting cells.

PMID- 8981441
TI  - Model of a thalamocortical neurone with dendritic voltage-gated ion channels.
AB  - To investigate the functional role of dendrites of thalamocortical neurones, we
      have used our one-compartmental model to construct a multi-compartmental model
      with dendritic regions chosen according to a representative soma-to-dendritic
      terminal path of an X cell of the cat dorsal lateral geniculate nucleus. The
      multi-compartmental model with dendritic low-threshold Ca2+ and delayed rectifier
      K+ channels yields more accurate results than the one-compartmental model when
      simulating tonic firing and oscillatory activities, and provides a useful means
      for the study of propagation of excitation on the dendrites.

PMID- 8981442
TI  - Lamin and beta-tubulin fragmentation precede chromatin degradation in glutamate
      induced neuronal apoptosis.
AB  - During ischaemic brain injury, glutamate accumulation with overstimulation of
      postsynaptic glutamate receptors and intracellular Ca2+ overload lead to neuronal
      death. We have shown previously that delayed neuronal death in cultures of
      cerebellar granule cells (CGCs) exposed to glutamate occurs by apoptosis. Here,
      we report that lamin cleavage and dissolution of the microtubule network precede
      chromatin fragmentation in glutamate-induced CGC apoptosis. Like other events
      that characterize excitotoxic cell death, degradation of lamins, beta-tubulin and
      disruption of microtubule architecture is inhibited by the NMDA-receptor
      antagonist MK-801. Our findings suggest that cleavage of key cytoskeletal
      elements is an important step in glutamate-induced neuronal apoptosis.

PMID- 8981443
TI  - Localization of ATP-gated ion channels in cerebellum using P2x2R subunit-specific
      antisera.
AB  - The distribution of the P2x2 purinoceptor subunit protein, which forms ATP-gated
      ion channels by homo- and hetero-multimeric assembly, was examined in the adult
      rat and guinea-pig cerebellum using two novel antisera generated against separate
      18 amino acid sequences located in the predicted extracellular domain of this
      subunit. These antisera, the first available for labelling the P2x2R subunit
      protein, were validated by selective labelling of a fusion protein containing the
      target amino acid sequences, and in cerebellum, by peptide specific block of
      immunoreactivity and by comparison with the distribution of P2x2R mRNA. P2x2R
      like immunoreactivity was seen in Purkinje cells, specifically the soma and
      dendrites, neurons in the granular and molecular layers and deep cerebellar
      nuclei. The identification of P2x2R-like immunoreactivity within the cerebellar
      neural circuitry is consistent with a role for extracellular ATP acting as a fast
      neurotransmitter in motor learning and coordination of movement. Additionally,
      labelling of neuroglia and fibre tracts supports a diverse role for extracellular
      ATP in CNS homeostasis.

PMID- 8981444
TI  - Characterization of cortical spreading depression by imaging of intrinsic optical
      signals.
AB  - The spatiotemporal progression of cortical spreading depression was investigated
      by imaging of activity-dependent intrinsic optical signals in rat sensorimotor
      cortex. In contrast to the traditional conception of a uniformly propagating
      event, the evolution of the spreading depression was characterized by an
      asymmetrical propagating wavefront and a non-uniform dispersion of optical
      signals behind the wavefront. As these optical signals are a reflection of
      underlying molecular and metabolic processes, the imaging approach to spreading
      depression might constitute a useful technique for investigating the functional
      organization as well the pathophysiology of the cerebral cortex.

PMID- 8981445
TI  - The neural adhesion molecule L1 is phosphorylated on tyrosine and serine
      residues.
AB  - The neural cell adhesion molecule L1 is highly homologous in its extracellular
      domain between species and completely identical in its cytoplasmic domain. We
      report here that tyrosine residues of L1 are phosphorylated in addition to serine
      residues, as determined by monoclonal phosphotyrosine antibodies and phosphoamino
      acid analysis. This result supports the suggestion that the cytoplasmic domain of
      L1 might be involved in signal transduction.

PMID- 8981446
TI  - NMDA receptor-mediated synapses between CA1 neurones: activation by ischaemia.
AB  - Using an in situ patch clamp in hippocampal CA1 mini-slices, we measured
      excitatory postsynaptic currents (EPSC) by varying the strength of the stimulus
      applied to the axons of CA3 neurones. The kinetics of the EPSC was initially
      independent of the stimulus strength. Post-ischaemic potentiation of the EPSC was
      observed 60-80 min after brief periods (10 min) of anoxia/aglycaemia. The decay
      of the EPSC slowed significantly in most of the examined neurones. In 11 of 17
      cells the EPSC kinetics became dependent on stimulus strength: a slower decay
      corresponded to a stronger stimulus. This effect was not abolished by N-methyl-D
      aspartate (NMDA) or a non-NMDA receptor blocker (D-2-amino-5-phosphonovaleric
      acid or 6-cyano-7-nitroquinoxaline-2,3-dione respectively) indicating the
      polysynaptic nature of the modified EPSC: transient ischaemia led to the long
      term recruitment of previously inactive, possibly latent NMDA synapses between
      CA1 neurones.

PMID- 8981447
TI  - GABA transamination regulates neuronal glutamate content in the retina.
AB  - We have used quantitative immunocytochemistry to examine the content of GABA and
      glutamate in rabbit retinae where the enzyme GABA transaminase has been
      selectively inhibited. Inhibition of GABA breakdown led not only to the expected
      rise in GABA levels in neurones and glial cells but also to a reduction in
      neuronal pools of glutamate, particularly in neuronal elements in the inner
      plexiform layer. We suggest that a significant proportion of the glutamate pool
      in nerve terminals is derived from GABA via the GABA shunt. This observation is
      of practical significance since GABA transaminase inhibitors are used in the
      treatment of epilepsy; accordingly GABA-transaminase inhibitors may modify
      uncontrolled excitatory episodes in the brain both by raising levels of GABA, and
      reducing levels of the excitatory transmitter, glutamate.

PMID- 8981448
TI  - Contribution of central 5-HT2 receptors in the occurrence of locomotor activity
      and myoclonia in freely moving rats exposed to high pressure.
AB  - Helium pressure of more than 20 bar is a well known cause of neuroexcitatory
      changes, referred to as the high pressure neurological syndrome. In rodents,
      symptoms include myoclonia and locomotor activity. In the present study, we used
      the 5-HT2A receptor antagonist ketanserin and the 5-HT2C receptor agonist m-CPP
      to investigate the role of central 5-HT2 receptors in the occurrence of these
      symptoms. Results suggest that 5-HT2A receptors and 5-HT2C receptors would play a
      crucial role in the development of myoclonia and locomotor activity,
      respectively. The selectivity of the drugs used, and the central origin of both
      myoclonia and locomotor activity are discussed.

PMID- 8981449
TI  - Microwave superheating enhances immunocytochemistry in the freshly frozen rat
      brain.
AB  - The goal of this study was to evaluate the effects of microwave irradiation on
      immunocytochemical staining in freshly frozen rat brain tissue using an antibody
      previously shown to successfully stain only formalin-fixed materials. GFAP
      immunoreactivity was markedly increased in sections exposed to microwave heating
      when compared with control tissue. Uniform staining enhancement was mainly a
      result of increased numbers of immunoreactive soma and large astrocytic
      processes. The integrity of the tissue was not affected by this treatment. Other
      antibodies need to be tested with this method, but our results suggest that
      microwave irradiation is useful for rapid antigen retrieval in freshly frozen
      central nervous system tissue.

PMID- 8981450
TI  - Imaging of Ca2+/calmodulin-dependent protein kinase II activity in hippocampal
      neurones.
AB  - Our aim was to visualize the dynamic features of Ca2+/calmodulin-dependent
      protein kinase II (CaMKII) activity. In order to do so, we synthesized a new
      reagent by conjugating a fluoroprobe, 6-acryloyl-2-dimethylaminonaphthalene
      (acrylodan), to syntide 2, a specific peptide substrate for CaMKII. In cell-free
      conditions, the conjugate was found to be an effective indicator of calmodulin
      activation by Ca2+ and the subsequent activation of CaMKII. The reagent is cell
      permeable and can stain living cells when bath-applied. Using this technique we
      were able to obtain fluorescence images of stained cells and analyse the dynamic
      features of CaMKII inside the cells by means of image processing. Regional
      heterogeneity of CaMKII activation in cultured hippocampal neurones was seen
      following L-glutamate administration.

PMID- 8981451
TI  - The non-peptide neuropeptide Y Y1 receptor antagonist BIBP3226 blocks the
      [Leu31,Pro34]neuropeptide Y-induced modulation of alpha 2-adrenoceptors in the
      nucleus tractus solitarii of the rat.
AB  - The potential blockade of the neuropeptide Y (NPY) Y1 receptor agonist
      [Leu31,Pro34]NPY-induced modulation of the characteristics of alpha 2
      adrenoceptor agonist [3H]p-aminoclonidine binding sites by a selective non
      peptide NPY Y1 receptor antagonist BIBP3226, was studied in the nucleus tractus
      solitarii of the rat by means of quantitative receptor autoradiography.
      [Leu31,Pro34]NPY at a concentration of 10 nM significantly increased the Kd value
      of [3H]p-aminoclonidine binding sites in the nucleus tractus solitarii without
      influencing the Bmax, suggesting the existence of an antagonistic modulation by
      NPY Y1 receptors of alpha 2-adrenoceptors in the nucleus tractus solitarii.
      BIBP3226 at 100 nM fully blocked the [Leu31,Pro34]NPY-induced increase in Kd of
      the [3H]p-aminoclonidine binding sites. The present results therefore provide
      evidence, by use of a NPY Y1 receptor antagonist, for the existence of a NPY
      Y1/alpha 2 receptor interaction in the nucleus tractus solitarii.

PMID- 8981452
TI  - Flip and flop isoforms of chick brain AMPA receptor subunits: cloning and
      analysis of expression patterns.
AB  - Using oligonucleotide primers, we have amplified and sequenced the alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors from the brain of 17
      day-old chick embryos. Both flip and flop isoforms of each of these glutamate
      receptors (GluR) were identified and cloned. Nucleotide comparisons showed that
      the two isoforms for each chick receptor subtype were 71-78% identical, whereas
      homologous chick and rat isoforms were 94-98% identical. Reverse transcriptase
      polymerase chain reaction and restriction enzyme analysis were employed to
      identify regional variation in flip and flop levels of each AMPA receptor. Flip
      isoforms of GluR 1-3 predominated in forebrain, while flop variants of GluR 1-4
      were more prevalent in the cerebellum. This differential regional expression
      suggests that alternative splicing of AMPA receptor subunits contributes
      importantly to synaptic diversity in chick central nervous systems.

PMID- 8981453
TI  - Saccade-related omnivectoral pause neurons in the primate zona incerta.
AB  - The zona incerta contains GABAergic neurons projecting directly on to collicular
      efferent neurons. This study examined the physiological characteristics of
      incertal neurons and their relationship to saccades. Cells in the zona incerta
      have moderate rates of activity and pause during saccades. These pauses begin
      prior to the start of saccades and activity resumes after the end of saccades in
      all directions and for all amplitudes. This perisaccadic pause is positively
      correlated with the duration of the saccade such that the longer the saccade is,
      the longer a pause is observed. These physiological data, in conjunction with
      anatomical observations, suggest that the zona incerta might normally function by
      inhibiting the superior colliculus and then by disinhibiting the superior
      colliculus for saccades.

PMID- 8981454
TI  - Region-specific serotonin1A receptor turnover following irreversible blockade
      with EEDQ.
AB  - The neurotoxicant N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)
      irreversibly inactivates serotonin1A (5-HT1A) receptors and is a useful tool to
      investigate the kinetics of receptor recovery following administration of the
      drug. Recovery characteristics were determined for 5-HT1A receptors located in
      the frontal cortex and hippocampus of male Sprague-Dawley rats treated with EEDQ
      (6.0 mgth kg-1, s.c.) or vehicle. Saturation binding assays using [3H]8-OH-DPAT
      were conducted, using frontal cortex and hippocampal membrane homogenates, at
      several time points following EEDQ treatment (1, 2, and 8 days post-injection).
      Scatchard analyses revealed region-specific differences in the recovery of these
      receptors. 5-HT1A receptors in the hippocampus degraded more quickly but
      recovered faster than those in the frontal cortex; receptor half-life was also
      shorter in the hippocampus than in frontal cortex. These regional variations are
      discussed in terms of differential receptor synthesis. The pathophysiological
      relevance of these findings to aging and disorders involving 5-HT1A receptor
      dysfunction, including depression and anxiety, is discussed.

PMID- 8981455
TI  - Susceptibility to drug-induced seizures of Fyn tyrosine kinase-deficient mice.
AB  - Mice deficient for the fyn gene were examined for their susceptibility to
      seizures induced by various convulsive drugs, including pentylenetetrazol,
      picrotoxin, bicuculline, kainic acid, N-methyl-D-aspartate (NMDA) and strychnine.
      Homozygous mutant (fynz/fynz) mice were significantly more likely to show
      myoclonic convulsions than were heterozygous mutants (+/fynz), when
      pentylenetetrazol, picrotoxin, bicuculline, kainic acid and NMDA were
      administered. On the other hand, no difference in seizure susceptibility was
      found between homozygous and heterozygous mutants when strychnine was
      administered. These results provide evidence of abnormal susceptibility to
      seizures induced by anti-GABAergic agents and agonists for central excitatory
      amino acids in Fyn-deficient mice.

PMID- 8981456
TI  - Expression of beta-amyloid precursor protein mRNAs following transient focal
      ischaemia.
AB  - beta-Amyloid precursor protein (beta APP) can be alternatively processed to
      result in release of either neurotoxic amyloid beta-peptide, or secreted forms of
      beta APP, which might have a role in neuronal plasticity and survival. Four
      different forms of beta APP mRNAs have been described in rodents: APP695, APP714,
      APP751 and APP770. The two larger forms contain a Kunitz-type serine protease
      inhibitor domain (KPI). Since previous studies have shown increased APP
      immunoreactivity following brain ischaemia, we used in situ hybridization
      histochemistry to determine whether induction of any APP mRNA transcripts take
      place following focal brain ischaemia. While the hybridization signal of all APP
      isoforms in the infarct was lost 4-24 h following the insult, APP770 mRNA was
      slightly upregulated in the ipsilateral cortex and striatum 3 days after 90 min
      ischaemia. At 7 days post-ischaemia APP770 and APP751 mRNAs were induced in the
      infarct core and in a thin perifocal zone. KPI-containing APP forms are
      differentially induced following focal brain ischaemia, possibly as a
      neuroprotective response to neuronal injury.

PMID- 8981457
TI  - Repetitive spreading depression causes selective suppression of GABAergic
      function.
AB  - Cortical spreading depression (SD) represents a pathophysiological signal that
      has been associated with the induction of migraine and ischaemic brain damage.
      The properties of repetitive SDs and their effects on excitatory and inhibitory
      synaptic transmission were analysed in neocortical slices obtained from adult
      rats. The SD showed only small variations in amplitude, duration and integral
      when elicited four times at intervals of 30 min. Extracellularly recorded paired
      pulse inhibition was, however, significantly reduced by approximately 10% with
      each SD episode. Since excitatory synaptic transmission was unaffected, our data
      indicate that repetitive SD causes a selective reduction of intracortical
      inhibition.

PMID- 8981458
TI  - Effects of in situ manipulation of nitric oxide on rat hippocampal CA3 neurone
      excitability.
AB  - THE response of hippocampal CA3 neurones to commissural stimulation, as expressed
      by the orthodromic population spike (PS2) recorded in anaesthetized rats, was
      increased when the recording micropipette contained the nitric oxide (NO)
      synthase inhibitor N omega-nitro-L-arginine methyl ester (20 mM). The increase
      was stable upon repeated stimulation. When the recording micropipette contained
      the NO donor sodium nitroprusside (SNP; 10 mM) the amplitude of PS2 elicited by
      low and middle stimulus strength (Istim) rapidly decreased, while remaining
      unchanged at higher Istim. When the SNP-containing microelectrode was maintained
      in place for longer, the depression of PS2 observed at low and medium Istim
      disappeared and PS2 increased at high Istim. This long-term SNP-induced increase
      in PS2 at high Istim was reduced by pretreatment with cycloheximide (5 mg kg-1,
      i.p.). These data, which provide the first demonstration that in situ
      manipulation of NO produces dual effects on neuronal responsiveness in a highly
      seizure-prone brain region, suggest that tonic levels of endogenous NO reduce the
      excitability of CA3 pyramidal neurones, whereas long-term overexposure to NO
      causes hyperexcitability possibly via genomic mechanisms.

PMID- 8981459
TI  - Comparison of nociceptive effects produced by intrathecal administration of mGluR
      agonists.
AB  - The present study examined the mGluR subtypes involved in (1S, 3R)-ACPD-induced
      spontaneous nociceptive behaviours (SNB) by administering the following selective
      agonists by the intrathecal (i.t.) route: (RS)-DHPG, trans-ADA (Group I; mGluR1/5
      and mGluR5, respectively), (1S, 3S)-ACPD, (2R, 4R)-APDC (Group II), and L-AP4
      (Group III). (RS)-DHPG administration induced SNB that were of significantly
      greater intensity and longer duration than those induced by an equal dose of (1S,
      3R)-ACPD. No other agonists produced SNB, except (1S, 3S)-ACPD, which may be
      attributable to a nonselective action at mGluR1. Intrathecal treatment with the
      mGluR antagonist (+)-MCPG or the NMDA antagonist D-AP5 prior to (RS)-DHPG
      administration dose-dependently reduced SNB. It is suggested that a possible
      interaction between NMDA and mGluR1 is a critical event in the maintenance of
      persistent nociception.

PMID- 8981460
TI  - Distribution of basal-expressed c-fos-like immunoreactive cells of the
      periaqueductal grey matter of the rat.
AB  - The distribution of c-fos proto-oncogene expression has been studied in the
      periaqueductal grey matter (PAG) of non-intentional-stimulated rats by
      immunohistochemistry. A mean number of 53 +/- 9 Fos-like immunoreactive cells per
      hemiPAG, distributed into three groups, dorsolateral, lateral and ventrolateral,
      was found. The dorsolateral and the lateral groups appeared along the entire
      rostrocaudal PAG, whereas the ventrolateral group appeared only in the caudal
      half. These results reveal new data on the number and extent of the longitudinal
      columns within the hypothetical organization of the PAG. They also indicate a
      continuous activation of a significant population of neurones in the PAG, in
      agreement with the suggested role of the PAG in the modulation of internal
      information.

PMID- 8981461
TI  - Associative learning down-regulates PKC beta 2- and gamma-immunoreactivity in
      astrocytes.
AB  - We showed previously that associative learning induced a twofold increase in
      protein kinase C gamma-immunoreactivity (PKC gamma-ir) in rabbit CA1 pyramidal
      neurons, whereas subicular neurons remained unchanged. Here, we investigated the
      effects of associative learning on PKC-positive astrocytes by determining their
      numerical density in the CA1 region and the subiculum of naive, pseudoconditioned
      and trace eyeblink conditioned rabbits. Associative learning induced a 70-80%
      reduction in the number of PKC beta 2- and gamma-positive astrocytes in the CA1
      region, but not in the subiculum. No changes were found in the number of PKC
      alpha- or beta 1-positive astrocytes in either hippocampal subregion. These
      results suggest a conditioning-specific downregulation of PKC beta 2 and gamma in
      a subset of astrocytes in a brain region where a simultaneous alteration in
      neuronal PKC gamma was evident.

PMID- 8981462
TI  - Rapid visual learning in neurones of the primate temporal visual cortex.
AB  - The human visual system can learn to recognize visual stimuli rapidly. For
      example, humans can accurately reconstruct meaningful objects out of fragmentary
      evidence, once they have seen the same object in its unambiguous form. The
      anterior temporal cortical areas of macaques contain some neurones with invariant
      visual responses which appear to provide a representation of complex patterns and
      objects, such as faces. Remarkably, these neurones show an enhancement of
      response after brief (e.g. 5 s) exposure to the unambiguous stimulus, an effect
      that appears to reflect the neural basis of the rapid perceptual learning seen in
      humans.

PMID- 8981463
TI  - The human cerebellum and temporal information processing--results from a PET
      experiment.
AB  - Changes of cerebellar blood flow were studied in normal humans using positron
      emission tomography (PET). A motor driven peg marked pairs of lines on subjects'
      right hands at different velocities. Subjects had to decide whether the second
      line was marked slower or faster than the first. Estimation of velocity (compared
      with control, i.e. presentation of lines at constant velocity) led to increases
      of regional cerebral blood flow (rCBF) in the left cerebellar hemisphere and
      vermis. Presentation of lines at constant velocity (compared with rest) activated
      the right cerebellar hemisphere. We conclude that the cerebellum is involved in
      temporal information processing even in the absence of motor output. This process
      can be separated from mere presentation of somatosensory stimuli.

PMID- 8981464
TI  - ERPs reveal deficits in automatic cerebral stimulus processing in patients with
      NIDDM.
AB  - We compared auditory event-related potentials (ERPs) and neuropsychological test
      scores in nine patients with non-insulin-dependent diabetes mellitus (NIDDM) and
      in nine control subjects. The measures of automatic stimulus processing,
      habituation of auditory N100 and mismatch negativity (MMN) were impaired in
      patients. No differences were observed in the N2b and P3 components, which
      presumably reflect conscious cognitive analysis of the stimuli. A trend towards
      impaired performance in the Digit Span backward was found in diabetic subjects,
      but in the tests of secondary or long-term memory the groups were comparable.
      Patients with NIDDM may have defects in arousal and in the automatic ability to
      redirect attention, which can affect their cognitive performance.

PMID- 8981465
TI  - Presynaptic NMDA receptors in the neocortex are both auto- and heteroreceptors.
AB  - We used electron microscopic immunocytochemistry with antibodies against NR1 and
      NR2A and B subunits to study the distribution of N-methyl-D-aspartate (NMDA)
      receptors in presynaptic axon terminals in the rat cerebral cortex. In all
      sections examined, NR1 and NR2A/B immunoreactivities were observed in axon
      terminals: NR1- and NR2A/B-positive axon terminals made both symmetrical and
      asymmetrical synapses on unlabelled dendritic profiles. Combined pre- and
      postembedding studies showed that all NR1 and NR2A/B-positive axon terminals
      making symmetrical synapses were gamma-aminobutyric acid (GABA)-positive. These
      observations show that both auto- and hetero- NMDA receptors do exist in the
      cerebral cortex, and indicate that part of the effects of NMDA receptor
      activation might be determined by modulating glutamate and GABA release.

PMID- 8981466
TI  - Oestradiol-induced taste avoidance is the result of a conditioned palatability
      shift.
AB  - Taste avoidances were conditioned in male rats by pairing ingestion of a novel
      sucrose (0.3 M solution) taste with injections of 17 beta oestradiol (100
      micrograms kg-1, s.c.). Following conditioning and prior to a two-bottle choice
      test (sucrose vs water), taste reactivity responses to three 30 s intraoral
      sucrose infusions were quantified. A robust conditioned shift in palatability,
      consisting of reduced ingestive and increased aversive taste reactivity
      responses, was obtained in the oestradiol group but not the vehicle control
      group. This conditioned palatability shift was also reflected in subsequent
      strong avoidance of the sucrose solution in the two-bottle choice test. The
      findings that oestradiol can condition taste aversions and shift food preferences
      support a role for oestrogens in the production of anorexia.

PMID- 8981467
TI  - NPY-Y1 receptor antisense injected centrally in rats causes hyperthermia and
      feeding.
AB  - The central actions of neuropeptide Y antisense oligodeoxynucleotide (aNPY) and
      NPY-Y1 receptor antisense (aNPY-Y1) on body temperature (Tb), feeding and body
      weight of unrestrained rats were determined by the repeated
      intracerebroventricular (i.c.v.) injection of 0.5 microgram doses. aNPY-Y1 caused
      intense phasic rises in Tb, lowered body weight and caused transient feeding.
      aNPY increased food intake paradoxically, accompanied by a gain in body weight
      but did not affect Tb. Circadian activity was unaffected by either antisense
      oligodeoxynucleotide, and the mismatched NPY (mNPY) was without effect. These
      results show that NPY-Y1 receptors underlie the central thermolytic action of
      NPY, since aNPY-Y1 induces hyperthermic responses. Overall, the functional
      reduction in NPY activity by aNPY might cause a compensatory de novo synthesis of
      NPY in structures remote from the ventricles to augment feeding behavior.

PMID- 8981469
TI  - Functional lateralization of speech production at primary motor cortex: a fMRI
      study.
AB  - To evaluate lateralization of speech production at the level of the Rolandic
      cortex, functional magnetic resonance imaging (1.5 Tesla, 27 parallel axial
      slices, EPI-technique) was performed during a speech task (continuous silent
      recitation of the names of the months of the year). As control conditions, non
      speech tongue movements and silent singing of a well-known melody with the
      syllable 'la' as its carrier were considered. Tongue movements produced
      symmetrical activation at the lower primary motor cortex. During automatic speech
      a strong functional lateralization to the left hemisphere emerged within the same
      area. In contrast, singing yielded a predominant right-sided activation of the
      Rolandic region. Functional lateralization of speech production therefore seems
      to include the precentral gyrus as well as Broca's area.

PMID- 8981468
TI  - Increased expression of cyclin D1 in the adult rat brain following kainic acid
      treatment.
AB  - Recent evidence has implicated aberrant cell cycle regulation as a possible
      mechanism of apoptosis in non-dividing cells. We previously demonstrated
      increased expression of the p53 tumor suppressor gene, a prominent cell cycle
      regulator, in apoptotic neurons. Here we investigated the potential involvement
      of cyclin D1, a G1 phase cell cycle protein under p53 regulation, in kainic acid
      mediated neuronal degeneration. Adult male Sprague-Dawley rats were treated
      systemically with kainic acid and sacrificed between 1 h and 5 days following
      seizure onset. Cyclin D1 expression was studied by Western blot analysis and
      immunohistochemistry using a rabbit polyclonal anti-cyclin D1 antibody. In
      untreated control rats low levels of cyclin D1 expression were detected in
      multiple brain regions. Between 8 and 16 h after the onset of kainic acid-induced
      seizures, increased cyclin D1 immunoreactivity was observed in vulnerable
      hippocampal pyramidal cells. Five days after seizure onset increased cyclin D1
      expression was evident in reactive astrocytes. These results support a role for
      cyclin D1 in certain neuronal death pathways, and suggest that cyclin D1 has
      multiple and cell type-specific functions in the central nervous system.

PMID- 8981470
TI  - PACAP immunoreactivity in the rat superior cervical ganglion in comparison to
      VIP.
AB  - The presence and regulation of pituitary adenylate cyclase activating peptide
      (PACAP) was investigated in the adult rat superior cervical ganglion. Double
      labelling immunofluorescence using specific antibodies against PACAP and
      vasoactive intestinal peptide (VIP) revealed a dense innervation of
      postganglionic sympathetic neurones by PACAP-immunoreactive but VIP-negative
      nerve endings that mainly were of preganglionic origin since they disappeared
      after transection of the cervical sympathetic trunk. Since PACAP regulates
      transmitter synthesis and release in sympathetic neurones in vitro, this finding
      provides a morphological correlate for modulatory effects of PACAP in vivo. Few
      neurones contained PACAP under normal conditions. However, the number of PACAP
      positive neurones increased in response to axotomy of the postganglionic nerves.
      Many of the newly PACAP-positive neurones also contained VIP, suggesting that
      both peptides are regulated by similar mechanisms.

PMID- 8981471
TI  - Activation of the prefrontal cortex during judgments of recency: a functional MRI
      study.
AB  - Animal and human lesion studies have consistently shown that damage to the
      prefrontal lobe disrupts performance on tasks requiring memory for temporal
      context. In this study, functional magnetic resonance imaging (fMRI) was used to
      explore the brain regions associated with judgements of relative recency in
      healthy humans. Bilateral dorsolateral prefrontal cortex (Brodmann's area [BA] 9)
      was more active during a verbal recency judgment task than during a non-mnemonic
      control task. Activation related to temporal context recognition was also
      observed in midline supplementary motor area (BA 6) and left precuneus (BA 7).
      This study provides further evidence that memory for temporal context requires
      the prefrontal cortex and is the first to demonstrate this association in healthy
      humans. The current findings also suggest the possibility that recognition of
      context and recognition of episodic content may involve similar brain systems.

PMID- 8981472
TI  - Spatial learning deficit in mice expressing human 751-amino acid beta-amyloid
      precursor protein.
AB  - Cognitive and other behavioural characteristics of 3-month-old heterozygous male
      transgenic mice expressing the 751-amino acid isoform of human amyloid precursor
      protein (hAPP751) under the control of a neurone-specific enolase promoter, were
      compared with those of age-matched non-transgenic control males. No difference
      was found between hAPP751 transgenics and non-transgenic controls in passive
      avoidance learning, or in motor coordination. Significantly decreased measures
      were found in the open field test and in cage activity indicative of general
      hypoactivity in hAPP751 transgenics. In water maze training, hAPP751 males
      required significantly longer to locate the hidden platform. This was not due to
      decreased swimming velocity in hAPP751 mice, but rather to increased path
      lengths. This suggests a purely spatial learning deficit in hAPP751 males even
      though their performance during a final spatial test, the probe trail that
      followed water maze training, was indistinguishable from that of controls.
      Decreased activity and impaired spatial learning were also reported in an
      independent study of hAPP751-expressing transgenics showing beta-amyloid
      immunoreactive deposits and altered tau protein. Since such histopathological
      alterations were not found in the transgenic model analysed in this study, our
      results indicate that beta-amyloid deposition is not required for the development
      of behavioural and/or cognitive deficits in hAPP751 transgenic mice.

PMID- 8981473
TI  - Basic fibroblast growth factor modulates in vitro differentiation of human fetal
      microglia.
AB  - The effects of basic fibroblast growth factor (bFGF) on differentiation of human
      fetal microglial cells were investigated. Human ramified microglial cells treated
      with human recombinant bFGF underwent a morphological change which resulted in a
      round-shape phenotype. bFGF was also able to induce a dose- and time-dependent
      increase in cell proliferation and enhanced phagocytic and non-specific esterase
      activity. These results indicate that ramified microglia, when properly
      stimulated, are regulated in their physiological and proliferative activities and
      are transformed into amoeboid forms. Growth factors, such as bFGF, are likely to
      play a key role in microglial transformation in both normal developing brain and
      in central nervous system injury.

PMID- 8981474
TI  - Regional and temporal modulation of brain glycoprotein synthesis by
      corticosterone.
AB  - Corticosterone has a biphasic effect on memory formation, short-term effects
      being facilitating and long-term effects resulting in cognitive impairments. The
      effects of different patterns of temporal exposure to corticosterone-previously
      shown to biphasically modulate water maze performance-on glycoprotein synthesis
      were evaluated in four rat brain regions: hippocampus, striatum, frontal cortex
      and hypothalamus. Acute corticosterone administration resulted in decreased
      glycoprotein synthesis in hippocampus and striatum, which might be related to the
      memory facilitating effects of the steroid. However, sustained exposure to
      corticosterone in a subchronic (7 days) or chronic (21 days) regimen indicated
      the hypothalamus as the only region displaying reduced fucosylation after chronic
      treatment. These findings suggest that detrimental effects of chronic
      corticosterone treatment on hippocampal neurones and memory might be not related
      to an initial steroid action on fucosyl-glycoprotein expression.

PMID- 8981475
TI  - Vagotomy blocks behavioural effects of interleukin-1 injected via the
      intraperitoneal route but not via other systemic routes.
AB  - To test specificity of the involvement of vagal afferents in the communication
      between the immune system and the brain, sham-operated and vagotomized mice were
      injected i.p., s.c. or i.v. with physiological saline or interleukin-1 beta (IL-1
      beta [symbol: see text] 4 weeks after surgery. Vagotomy attenuated the decrease
      in social exploration induced by i.p. injection of 300 ng recombinant human IL-1
      beta but had no effect when IL-1 beta was injected s.c. (300 ng) or i.v. (500
      ng). Vagotomy also attenuated the depression in social investigation induced by
      i.p. injection of recombinant rat IL-1 beta (IL-1 beta, 1 microgram) but was
      without effect when 1 microgram IL-1 beta was injected i.v. These results confirm
      the role of vagal afferent nerves in the transmission of an immune message from
      the periphery to the brain and show that the vagus nerve only conveys information
      concerning cytokines injected into the abdominal cavity.

PMID- 8981476
TI  - Pre- and peristroke treatment with the adenosine kinase inhibitor, 5'
      deoxyiodotubercidin, significantly reduces infarct volume after temporary
      occlusion of the middle cerebral artery in rats.
AB  - The adenosine kinase inhibitor, 5'-deoxyiodotubercidin (5dITU), was examined in a
      rat focal stoke model with temporary (105 min) middle cerebral artery occlusion
      (MCAO) followed by a 24 h recovery period. Inhibition of this adenosine
      metabolizing enzyme indirectly enhances the actions of endogenous adenosine
      without inducing cardiovascular side effects. Such effects could limit the
      potential clinical application of any approach targeting adenosine receptor
      activation. MCAO was accomplished with a transluminal 4-0 nylon suture inserted
      through the common carotid artery to block blood flow at the origin of the MCA.
      Treatment with 5dITU 30 min prior to and 5 h after MCAO resulted in a dose
      dependent (0.1-0.5 mg/kg, i.p.) reduction in infarct volume. A significant (P =
      0.02) 44% reduction (control, 265 +/- 35 mm3; treated, 149 +/- 30 mm3) was
      observed at 0.5 mg/kg. However, at the highest dose examined (1.0 mg/kg) infarct
      volume was unaffected. To assess the potential for acute (i.e. post-occlusion)
      treatment, 5dITU was administered (0.33 mg/kg, i.v.) successively at each of 0.5,
      1.75 and 3.5 h after MCAO. Post-occlusion treatment resulted in a significant (P
      = 0.037) 32% reduction in infarct volume (control, 314 +/- 34 mm3; treated, 212
      +/- 28 mm3). At this dose there were no apparent changes in a number of
      physiological parameters monitored over the period of MCAO. The present study
      shows that intervention with an adenosine kinase inhibitor in an ischemic brain
      injury model is neuroprotective whether treatment is begun prior to or just after
      MCAO.

PMID- 8981477
TI  - Accumulation of tyrosine hydroxylase messenger RNA molecules in the rat
      mesencephalon by chronic caffeine treatment.
AB  - In the present study we assessed the effect of chronic treatment with caffeine on
      the levels of the messenger RNA molecule encoding the enzyme tyrosine hydroxylase
      (TH) by in situ hybridization histochemistry in the ventral tegmental area (VTA)
      and the substantia nigra compacta (SNc) of the rat brain. Animals that received
      caffeine for nine consecutive days at doses of 20, 40 and 80 mg/kg of body weight
      displayed increased TH mRNA levels in the SNc (up to 64% above vehicle-injected
      controls) and the VTA (33% above controls). Moreover, the increases observed at
      80 mg/kg of caffeine were prevented by concurrent administration of the non
      competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (0.25 mg/kg).
      These results demonstrate that chronic exposure to caffeine, an adenosine A2
      receptor antagonist, alters the levels of expression of the mRNA encoding the
      rate limiting enzyme in catecholamine biosynthesis.

PMID- 8981478
TI  - Cell intrinsic mechanisms regulate mouse cerebellar granule neuron
      differentiation.
AB  - Cerebellar granule cells isolated from postnatal day 7 mice, and cultured in
      minimal medium containing only insulin-like growth factor-I (IGF-I), both survive
      and differentiate. This differentiation is marked by neurite growth and
      expression of genes associated with terminal differentiation, the myocyte
      specific enhancer factor 2A (MEF2A) and the alpha 6 subunit of the gamma
      aminobutyric acidA receptor (GABAA alpha 6). Percoll gradient purified granule
      cells maintained without IGF-I, in minimal medium alone or in medium containing
      the antioxidant N-acetylcysteine (NAC), also express MEF2A and GABAA alpha 6.
      Thus, cultured granule neurons can differentiate to some extent cell-autonomously
      and IGF-I may not be a critical factor for this process.

PMID- 8981479
TI  - Apoptotic neuron death in rat substantia nigra induced by striatal excitotoxic
      injury is developmentally dependent.
AB  - We have previously observed that an axon-sparing lesion of the striatum during
      development is associated with an induction of apoptotic cell death in the
      substantia nigra (SN). We have postulated that the induced death is due to a loss
      of striatum-derived trophic support. In other paradigms of neural development, it
      is often found that a need for trophic support is primarily observed only during
      a critical development period. We have therefore examined the time course for
      early striatal lesion to induce cell death in substantia nigra. We find that
      induction of apoptotic cell death is largely restricted to the first 2 postnatal
      weeks. After that time, induction of death in SN pars compacta abates. In SN pars
      reticulata, apoptotic death also abates, but by postnatal day 28, a non-apoptotic
      morphology of death appears. Thus, induced apoptotic death in SN is restricted to
      a critical developmental period.

PMID- 8981480
TI  - Antisense blockade of inducible nitric oxide synthase in glial cells derived from
      adult SJL mice.
AB  - Increasing evidence suggests a correlation between cytokine-induced nitric oxide
      synthase (iNOS) and demyelination in Multiple sclerosis (MS). Inhibition of iNOS
      may therefore be a novel therapeutic approach in MS. To test an antisense
      oligodeoxynucleotide (ODN) knockdown strategy for inhibiting iNOS, we used
      lipopolysaccharide (LPS) together with gamma-interferon (IFN-gamma) to induce
      iNOS in adult mouse mixed glial cell cultures. We administered an iNOS-derived
      antisense phosphorothiorate oligodeoxynucleotide (S-ODN) to block the induction.
      The antisense ODN treatment resulted in significant inhibition of LPS and IFN
      gamma induced iNOS mRNA and protein expression. It also inhibited nitric oxide
      (NO) and cyclic GMP (cGMP) production in a dose dependent fashion. Sense and
      random S-oligo had no effect in any of these studies. These data indicate the
      efficacy and specificity of the antisense oligodeoxynucleotide approach in
      inhibiting iNOS in glial cells.

PMID- 8981481
TI  - Thermal hyperalgesia in rat evoked by intrathecal substance P at multiple
      stimulus intensities reflects an increase in the gain of nociceptive processing.
AB  - Substance P (SP) is associated with primary afferent depolarization after a
      noxious or tissue-damaging peripheral stimulus and is proposed to be a "pain
      transmitter'. However, current work has shown that activation of spinal
      neurokinin receptors evokes few signs of "pain behavior', but rather decreases
      nociceptive thresholds, suggesting a modulatory role through additive or
      multiplicative mechanisms. The current study addressed this question by examining
      the change in nociceptive threshold under three different radiant thermal stimuli
      after intrathecal SP administration in unanesthetized rats. With increasing
      stimulus intensity, the numerical change in withdrawal latency after intrathecal
      SP decreased, but the fractional change from baseline latency did not change,
      suggesting that SP increases the gain of spinal nociceptive processing.

PMID- 8981482
TI  - Non-rapid eye movement sleep is suppressed in transgenic mice with a deficiency
      in the somatotropic system.
AB  - Sleep-wake activity was studied in a transgenic mouse model (TH-hGH) with a
      deficiency in the somatotropic axis (growth hormone (GH)-releasing hormone (GHRH)
      GH-insulin-like growth factor-I (IGF-I)). This dwarf transgenic mouse strain
      expresses a human GH (hGH) reporter gene linked to 4.8 kb of the rat tyrosine
      hydroxylase flanking sequence, targeting the production of hGH to sites of
      tyrosine hydroxylase synthesis in the brain. Endogenous GH and IGF-I are
      suppressed in these mice, as well as GHRH. Sleep-wake activity (EEG and EMG) was
      recorded for 2 to 3 days in nine transgenic mice and nine wild-type littermates.
      Non-rapid eye movement sleep (NREMS) was significantly suppressed during both the
      light and the dark period in the transgenic mice; rapid eye movement sleep (REMS)
      was not altered. The results provide evidence that the somatotropic axis
      contributes to normal sleep regulation.

PMID- 8981483
TI  - Characterisation of the rat cerebella CB1 receptor using SR141716A, a central
      cannabinoid receptor antagonist.
AB  - We describe the use of SR141716A, a central cannabinoid antagonist, in
      radioligand binding and adenylyl cyclase (AC) inhibition studies in rat cerebella
      membranes. The binding of [3H]SR141716A was dose-dependent and saturable, with Kd
      and Bmax of 0.61 +/- 0.12 nM and 1752 +/- 294 fmol/mg protein, respectively.
      Kinetic analysis of [3H]SR141716A binding afforded a Kd of 0.72 nM. In addition
      [3H]SR141716A was displaced dose-dependently by unlabelled SR141716A yielding a
      pKi of 8.37 +/- 0.07. Cannabinoid receptor agonists displaced [3H]SR141716A in a
      dose-dependent manner, (pKi) nabilone (8.29 +/- 0.08), WIN 55,212-2 (7.75 +/-
      0.15), delta 9-tetrahydrocannabinol (7.29 +/- 0.21), delta 8-tetrahydrocannabinol
      (6.53 +/- 0.09) and anandamide (5.92 +/- 0.04). The affinity of anandamide was
      increased (6.26 +/- 0.13) by co-incubation with a serine protease inhibitor. A
      range of 13 commonly used non-cannabinoid ligands included at 100 microM were
      unable to displace [3H]SR141716A. WIN 55,212-2 inhibited basal cAMP formation
      dose-dependently with a pIC50 of 7.61 +/- 0.12 (24.3 nM) in an SR141716A (1
      microM) reversible manner.

PMID- 8981484
TI  - Projections from the ventrolateral periaqueductal gray to endocrine regulatory
      subdivisions of the paraventricular nucleus of the hypothalamus in the rat.
AB  - The ventrolateral periaqueductal gray (vlPAG) mediates quiescence,
      hyporeactivity, hypotension and bradycardia, a pattern of response evoked by
      injury or social defeat. These stimuli also evoke increased levels of vasopressin
      (VP) and adrenocorticotrophic hormone (ACTH). A key central nervous system (CNS)
      locus mediating endocrine changes is the paraventricular nucleus of the
      hypothalamus (PVH). We investigated the extent of vlPAG projections to PVH.
      Anterograde tracer injections into the vlPAG, revealed 'terminal' label in: (1)
      the medial, dorsal, anterior and lateral parvicellular divisions, and (2) lateral
      and medial posterior magnocellular divisions of the PVH. Deposits of the
      retrograde tracer Fast Blue, verified the projection to the PVH arising from the
      vlPAG.

PMID- 8981485
TI  - Bulbar representation of the 'water-nose' during Xenopus ontogeny.
AB  - Olfactory epithelium that is specialized for the detection of water-borne odors
      is located in different cranial cavities in larval and postmetamorphic Xenopus.
      Soybean agglutinin histochemistry reveals that both "water-noses' innervate only
      the ventral olfactory bulb (OB). This is evidence for a parcellation of the OB
      into a ventral portion mediating information on water-soluble odorants and a
      dorsal part that processes information on volatile substances.

PMID- 8981486
TI  - Inhibition of calcium channels in rat hippocampal CA1 neurons by conantokin-T.
AB  - Effects of conantokin-T, a 21 amino acid peptide toxin isolated from the fish
      hunting cone snail Conus tulipa, on the high-voltage-activated Ca2+ channel
      currents were studied in acutely dissociated rat hippocampal CA1 neurons using
      whole-cell voltage clamp-recording technique with 5 mM Ba2+ as the charge
      carrier. Conantokin-T inhibited the whole-cell Ba2+ current (IBa) in a
      concentration-dependent manner. The nimodipine (20 microM) and omega-agatoxin-IVA
      (0.2 microM) block of IBa were abolished in the presence of conantokin-T (3
      microM); however, conantokin-T (3 microM) did not affect the block of IBa induced
      by 3 microM omega-conotoxin-GVIA. These results indicate that conantokin-T is a
      potent but wide-spectrum Ca2+ channel antagonist.

PMID- 8981487
TI  - Inhibition of synaptosomal veratridine-induced sodium influx by antidepressants
      and neuroleptics used in chronic pain.
AB  - Veratridine-induced (10 microM) increases in intracellular sodium ([Na+]int) or
      calcium ([Ca2+]int) in rat cortical synaptosomes, measured with the fluorescent
      dyes SBFI or FLUO-3 were blocked by tetrodotoxin (IC50 Na+ 14 nM; Ca2+ 20 nM) and
      by a series of reference sodium channel blockers with neuroprotective (riluzole,
      lifarizine IC50 approximately 1-5 microM), anticonvulsant (lamotrigine, phenytoin
      IC50 approximately 70-140 micro M), local anaesthetic (lidocaine, procaine IC50
      approximately 60-200 microM) or antiarrhythmic properties (quinidine,
      disopyramide, amiodarone, mexiletene, propafenone, fleicainide IC50,
      approximately 2-200 microM). Potencies for inhibition of veratridine-induced
      sodium and calcium entry were closely matched. These agents did not, or only
      weakly blocked, potassium evoked (50 mM) increases in [Ca2+]int. A number of
      antidepressant monoamine uptake inhibitors (amitriptyline, fluoxetine,
      clomipramine, desipramine, imipramine) or neuroleptics (pimozide, cinnarizine,
      haloperidol) were also potent inhibitors of veratridine-induced increases in
      [Na+]int or [Ca2+]int with affinities ranging from approximately 1-10 microM. A
      number of these drugs, from diverse chemical and pharmacological classes, are
      used for the treatment of chronic pain and their mechanism of action could
      perhaps be related to their common effects on a particular species of neuronal
      sodium channel.

PMID- 8981488
TI  - Involvement of sphingolipids in the endothelin-1 signal transduction mechanism in
      rat brain.
AB  - In cerebral cortex, endothelin-1 (ET-1) evoked a decrease of 40% in sphingomyelin
      (SM) levels together with an increase in both ceramide and glycosphingolipid
      (GSL) levels (100 and 56% respectively). These facts indicate that ET-1 increases
      sphingomyelinase activity and, possibly, activates the synthesis of GSL. By
      contrast, in cerebellum ET-1 seems to activate the hydrolysis of both SM and GSL,
      since the peptide evoked a decrease (near 30%) of their levels concomitantly with
      an increased production of ceramides (200%). These ceramides are clearly
      different from those produced in cerebral cortex which come from the SM
      hydrolysis only. It is suggested that ETB receptor subtype is involved in these
      responses.

PMID- 8981489
TI  - Serum growth factor regulation of the paired-box transcription factor Pax-3 in
      neuronal cells.
AB  - Mutations in the murine Pax (paired-box)-3 gene results in a number of
      developmental abnormalities including a deficiency in sensory neurons. To
      determine the role that Pax-3 plays in neuronal cell development, we have studied
      the expression of Pax-3 in the ND7 neuronal cell line. Upon serum starvation, Pax
      3 mRNA expression fell rapidly. Within 2 h of the removal of serum a 2-3-fold
      decrease in Pax-3 expression was observed and by 6 h Pax-3 mRNA expression was
      undetectable. Interestingly this decrease in Pax-3 expression could be reversed
      by the addition of serum growth factors. This rise in Pax-3 expression upon
      growth factor addition, was followed by an increase in cell proliferation and a
      reduction in neurite outgrowth, suggesting that Pax-3 may play a role in
      mediating cellular responses to these factors in neuronal cells.

PMID- 8981490
TI  - Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single
      bright light exposure in humans.
AB  - Eight young males were subjected to a single blind cross-over test to see the
      effects of vitamin B12 (methylcobalamin; VB12) on the phase-response of the
      circadian melatonin rhythm to a single bright light exposure. VB12 (0.5 mg/day)
      or vehicle was injected intravenously at 1230 h for 11 days, which was followed
      by oral administration (2 mg x 3/day) for 7 days. A serial blood sampling was
      performed under dim light condition (less than 200 lx) and plasma melatonin
      rhythm was determined before and after a single bright light exposure (2500 lx
      for 3 h) at 0700 h. The melatonin rhythm before the light exposure showed a
      smaller amplitude in the VB12 trial than in the placebo. The light exposure phase
      advanced the melatonin rhythm significantly in the VB12 trail, but not in the
      placebo. These findings indicate that VB12 enhances the light-induced phase-shift
      in the human circadian rhythm.

PMID- 8981492
TI  - Effects of indomethacin on cerebral blood flow and oxygen metabolism: a positron
      emission tomographic investigation in the anaesthetized baboon.
AB  - The aim of this study was to clarify the controversy about the effects of
      indomethacin on the coupling of cerebral blood flow (CBF) to cerebral oxygen
      metabolism (CMRO2). CBF, blood volume (CBV), oxygen extraction fraction (OEF) and
      CMRO2 were measured by positron emission tomography (PET) in five anaesthetized
      baboons before and during an i.v. administration of indomethacin (bolus 20 mg/kg
      followed by perfusion 10 mg/kg.h). Administration of indomethacin resulted in a
      marked and homogenous decrease of CBF in every region analysed (-28% to -40%) and
      a moderate reduction in CBV (-8% to -16%). In contrast, CMRO2 displayed a small
      increase in thalamus and pons (+10% and +13%, respectively). OEF increased
      greatly in all structures studied (+59% to +96%). These findings show that the
      potent cerebrovascular effects of indomethacin are not related to a decrease in
      CMRO2 as measured through the use of PET.

PMID- 8981491
TI  - Down-regulation of endogenous nitric oxide synthase in late-pregnancy and
      parturition in the rat hypothalamic magnocellular neurons and neurohypophysis.
AB  - Several recent lines of evidence suggest that nitric oxide (NO) may be an
      endogenous inhibitory regulator of the neurosecretory mechanism in magnocellular
      neurons of the paraventricular and the supraoptic nuclei in the hypothalamus. The
      NO synthase (NOS) system in the hypothalamo-neurohypophysial-axis is regulated in
      an activity-dependent manner. The present study examined NOS activity in the
      magnocellular neurons and neurohypophysis during pregnancy and parturition by
      using the nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase
      histochemistry and assay of the specific NOS enzyme activity, respectively. In
      the paraventricular and supraoptic nuclei, the density and number of NADPH
      diaphorase-positive cells decreased in late-pregnancy and parturition. The
      specific activity of NOS in the neurohypophysis also decreased in late-pregnancy
      through parturition, and increased shortly afterward. Together with the ability
      of a NO donor to significantly delay the progress of parturition when
      administered centrally in parturient rats, these observations suggest that this
      down-regulation of NOS activity in the hypothalamo-neurohypophysial axis in late
      pregnancy and parturition may be of physiological importance in the onset and/or
      progress of parturition.

PMID- 8981493
TI  - Nicotine increases [Ca2+]i and regulates electrical activity in insect
      neurosecretory cells (DUM neurons) via an acetylcholine receptor with 'mixed'
      nicotinic-muscarinic pharmacology.
AB  - An increase in intracellular free calcium concentration ([Ca2+]i) was observed
      following the application of nicotine to isolated adult dorsal unpaired median
      (DUM) neurons of the cockroach (Periplaneta americana) terminal abdominal
      ganglion (TAG) using Fura-2 fluorescence measurements. Bath-applied nicotine (1
      mM) induced a transient increase in [Ca2+]i. Calcium responses to bath-applied
      nicotine were blocked completely by alpha-bungarotoxin (100 nM) and were reduced
      by 50% in the presence of pirenzepine (1 microM). The sensitivity of the response
      to both nicotinic and muscarinic antagonists suggested that it was mediated by an
      acetylcholine receptor with 'mixed' pharmacology. In whole cell current-clamp
      experiments, nicotine reduced the frequency of evoked action potentials by
      decreasing the slope of the predepolarization in the last two-thirds of the
      pacemaker potential. Voltage-clamp studies revealed that nicotine modified the
      inactivation properties of the maintained low-voltage-activated (LVA) calcium
      current increasing the rate of relaxation of this current and transforming a U
      shaped voltage dependence of inactivation into a monotonic relationship to
      voltage. These effects were blocked when isolated DUM neurons were pretreated
      with 0.5 microM alpha-bungarotoxin. Our findings suggested a novel calcium
      dependent regulation of firing behavior in TAG DUM neurons following activation
      of an acetylcholine receptor with 'mixed' pharmacology, resulting in a rise in
      [Ca2+]i which reduces firing frequency by modulating a maintained LVA calcium
      current responsible for the action potential predepolarization.

PMID- 8981494
TI  - Teaching is not feeding.

PMID- 8981495
TI  - Stages of nursing's political development: where we've been and where we ought to
      go.

PMID- 8981496
TI  - Meta-analysis and public policy: opportunity for nursing impact.

PMID- 8981497
TI  - Highlighting the role of policy in nursing practice through a comparison of "DNR"
      policy influences and "no CPR" decision influences.

PMID- 8981498
TI  - An implicit world view in technology and its consequences for contemporary life.
AB  - To summarize, when the technological way of thinking is taken to the extreme it
      becomes a world view that is associated with a particular danger, in that it is
      not taken by its proponents as one of many competing world views but is
      considered uncritically to be a fact, not a hypothesis. Through a series of
      applications of the fallacy of hypothesis/fact confusion and through uncritical
      use of the technological frame of mind, one can inevitably become committed to an
      overarching physicalism, materialism, mechanicalism, and determinism, perhaps
      without even knowing that one has such afflictions. My own discipline,
      philosophy, which I regard as a science in the broad sense previously mentioned,
      has not escaped being captured by this technological mind-set, much to its
      detriment. I refer readers who are interested in the plight of philosophy in this
      age to the works of Hilary Putnam, Bruce Wilshire, Ludwig Wittgenstein, or
      Charles Peirce. I take this step because I am not a machine, and if I didn't stop
      now, I would feel guilty about taking too much of your time.

PMID- 8981499
TI  - Florence Nightingale's influence on the development and professionalization of
      modern nursing in Japan.
AB  - This article has summarized the overwhelming sociocultural and geopolitical
      forces that influenced the development of modern nursing in Japan. The irony of
      Japanese nursing is that modern nursing, first introduced by navy physicians,
      served the needs of Japanese military efforts and those of physicians who
      required others to perform menial hospital chores. Because of the harsh realities
      of nursing in the battlefields or in hospitals, working as a Kangofu was, and is,
      not compatible with a traditional family life. Like Nightingale, the majority of
      active Kangofus, especially the leaders in the profession, are unmarried. The
      major impact of Nightingale on Japanese nurses has been in her role as a
      spiritual icon, giving nurses the strength to survive in the face of enormous
      hardship. The true professionalization of nursing in Japan lies on the horizon,
      110 years after Nightingale's work was introduced in Japan and 50 years after
      Japan became a democratic country. Toward this new vision for nursing, I offer
      the Hokenfu model rather than the traditional Kangofu model, under which Japanese
      nurses have suffered oppression and discrimination for a century. In conclusion,
      Japanese nurses should expand their perspective on their profession and seize the
      opportunity for reform that now tantalizingly presents itself, not only to best
      serve their patients but also to fulfill their own potential as respected health
      professionals-potential that is, as of now, unrealized.

PMID- 8981500
TI  - Interleukin-6 is a useful marker for early prediction of the severity of acute
      pancreatitis.
AB  - Twelve patients with acute pancreatitis admitted to our department between
      January 1993 and December 1994 were studied prospectively and classified into two
      groups (severe group, five patients; mild group, seven patients), according to
      the criteria for grading severity of acute pancreatitis proposed by the Research
      Committee for Intractable Diseases of the Pancreas, Japanese Ministry of Health
      and Welfare (1990). To evaluate markers for early estimation of the severity of
      acute pancreatitis, we measured serum changes in various parameters. In the
      severe group interleukin-6 (IL-6) levels were increased significantly 5, 24, 72,
      and 120 h after the onset (p < 0.01), compared with the mild group. C-reactive
      protein (CRP), thrombin antithrombin III, and alpha 2-plasmin inhibitor plasmin
      complex levels were significantly increased only at the 72-h time point. Peak
      values of interleukin-8 (IL-8) and soluble human E selectin were observed at 5
      and 72 h, respectively, after the onset. There was a significant correlation
      between IL-6 at 5 h and both pancreatic secretory trypsin inhibitor (r = 0.85)
      and CRP (r = 0.94) at 72 h. We therefore conclude that IL-6 is a useful marker
      for assessment of the severity of acute pancreatitis in its early stages.

PMID- 8981501
TI  - Prognostic role of 99mTc-HM-PAO-leukocyte scintigraphy in acute pancreatitis and
      in patients with pancreatic pseudocysts.
AB  - Fifty-five leukocyte scintigraphies were performed. Thirty-five patients (group
      1) with acute pancreatitis in the early phase and 20 patients (group 2) with
      pancreatic chronic pseudocysts following acute pancreatitis were tested. The
      clinical features, laboratory parameters, and Ranson classifications were
      registered during hospitalization. In group 1, most of the cases with a severe
      clinical outcome gave positive leukocyte scintigraphic results (10/12). Leukocyte
      accumulation was also detected in patients with mild acute pancreatitis (4/23),
      but at a lower frequency. In the acute phase, significant differences in
      laboratory parameters (sedimentation rate and leukocyte count) were found in the
      leukocyte scintigraphy-positive versus-negative cases. The scintigraphic activity
      correlated with the sedimentation rate, leukocyte count, fever, and duration of
      hospitalization. In group 2 there were five cases with a positive leukocyte scan.
      A pancreatic abscess was found in four of them during surgery. In seven patients
      with a normal scintigram, surgery revealed a noninfected pancreatic pseudocyst.
      Leukocyte infiltration of the pancreas can be demonstrated by leukocyte
      scintigraphy. A positive leukocyte scan indicated a severe course of acute
      pancreatitis. The method also seems useful for differentiation between infected
      and noninfected chronic pancreatic pseudocysts.

PMID- 8981502
TI  - Common biliary-pancreatic conduit stenosis induces pancreobiliary reflux.
AB  - A striking pancreatic juice reflux toward the biliary tree (PR) has frequently
      been found in subjects with common bile-pancreatic conduit (CBPC) and gallstone
      induced acute pancreatitis (SAP). Our aim was to determine the role of the CBPC
      functional diameter as a potential trigger of PR. The CBPC was calibrated in
      three groups of patients: (A) patients with gallbladder stones using
      intraoperative direct cholangiometry (n = 24), (B) patients after surgical
      removal of common bile duct stones using postoperative cholangiometry via T-drain
      (n = 6), and (C) patients with SAP using the same procedures as in group B (n =
      6). In all patients in groups B and C, aliquots of bile were collected and
      assayed for pancreatic amylase content. The mean functional diameter of the CBPC
      varied from 0.80 mm in patients in groups A and B to 0.47 mm in group C (p <
      0.001). The bile samples of group B contained low concentrations of amylase,
      whereas high values could be found in all samples of group C. We conclude that PR
      is a frequent event occurring after bile duct revision concerning small amounts
      of pancreatic juice. However, CBPC functional stenosis as seen in patients with
      SAP obviously induces PR with high amounts of pancreatic juice.

PMID- 8981504
TI  - Endoscopic sphincterotomy and recurrence of acute pancreatitis in gallstone
      patients considered unfit for surgery.
AB  - The aim of the present prospective study was to investigate whether endoscopic
      sphincterotomy may be useful in preventing recurrence of acute pancreatitis in
      patients with gallstones and a high anesthesiological risk of cholecystectomy.
      Twenty-six elderly patients with severe cardiopulmonary, hepatic, and renal
      diseases were considered. Endoscopic sphincterotomy was successful in 19 cases
      (group A: mean age, 78.4 years; range, 71-87) and failed in 7 patients (group B:
      mean age, 79.8 years; range 73-85). In the follow-up period biliary pain without
      an increase in pancreatic serum enzymes occurred in six patients in group A and
      in all patients in group B (p = 0.002); recurrence of acute biliary pancreatitis
      with a need for hospitalization occurred in one patient in group A and in four
      patients in group B (p = 0.01). These results suggest that endoscopic
      sphincterotomy may be considered a very useful option in reducing the recurrence
      of acute biliary pancreatitis in elderly patients with gallstones and a high
      anesthesiological risk of cholecystectomy.

PMID- 8981503
TI  - Lysosomal aspartic and cysteine proteinases serum levels in patients with
      pancreatic cancer or pancreatitis.
AB  - Lysosomal cathepsins D (CD), B (CB), and L (CL) serum levels were determined by
      immunoassays in patients with chronic (CHP) or acute (AP) pancreatitis and in
      patients with ductal pancreatic carcinoma (DPC) and correlated with some
      biological and clinical parameters of this tumor. CB serum concentrations
      significantly higher than those measured in healthy subjects (NS) were observed
      in CHP, AP, and DPC patients (p < 0.01). However, no significant difference was
      noted among these groups. Increased CL serum levels were evident only in cancer
      patients compared to NS, AP, or CHP groups (p < 0.05), while no difference was
      observed among these groups. Elevated CD serum values were observed in CHP and AP
      patients compared to healthy subjects or cancer patients (p < 0.01). In cancer
      patients no correlation between CD, CB, and CL and clinical stage or tumor size
      was found. However, significant correlations were observed only between serum CD
      and CA50 (p < 0.02) and between CD and CL (p < 0.05). No further relationship
      among the biochemical parameters examined was observed. The present data suggest
      that the different serum patterns of CD, CB, and CL in patients with pancreatitis
      and pancreatic cancer may be of clinical interest as additional biochemical
      parameters for the differential diagnosis of these diseases. However, further
      prospective clinical studies are needed to assess better their potential value as
      prognostic parameters to identify patients with pancreatitis at increased risk to
      develop pancreatic cancer.

PMID- 8981505
TI  - Similar morphological and intracellular biochemical changes in alcoholic acute
      pancreatitis and ischemic acute pancreatitis in rats.
AB  - Pancreatic hyperstimulation with simultaneous duct obstruction does not cause the
      typical features of acute pancreatitis, therefore the role of an additional
      challenge, such as either ethanol intoxication or short-term ischemia, was
      studied. Alcoholic pancreatitis was induced in 28 rats by acute ethanol
      intoxication (0.25 LD50) and an obstruction/hyperstimulation mechanism (clip of
      the biliopancreatic duct for 20 min and intravenous stimulation with 5 U of
      cholecystokinin and secretin each). Ischemic pancreatitis was performed by
      obstruction/hyperstimulation and subsequent pancreatic ischemia by clamping the
      supplying arteries for 40 min. The macro- and microscopic alterations were
      evaluated and graded by a scoring system. Additionally, the pancreas was removed
      in 50% of the animals and the pancreatic acini were prepared. From those acini
      the intracellular enzymes trypsinogen, kallikreinogen, amylase, lipase,
      glucuronidase, and acidic phosphatases were determined. While
      obstruction/hyperstimulation, 40 min of ischemia, or ethanol alone did not induce
      acute pancreatitis, a combination of obstruction/hyperstimulation with either
      ethanol or ischemia resulted in acute pancreatitis in 68 and 60% of treated rats,
      respectively. Similarly, both models were characterized by extrapancreatic fat
      necrosis and acinar necrosis at the periphery of the lobules. Almost all
      intracellular enzymes were elevated in both pancreatitis models compared to sham
      operated controls. Both alcohol and ischemia were insults that sensitize the
      pancreas to develop acute pancreatitis after obstruction/hyperstimulation. Since
      the observed morphologic and enzymatic alterations in both models are very
      similar, alcohol and ischemia might have some common pathways by which they make
      the pancreas vulnerable to enzymatic attacks.

PMID- 8981506
TI  - Role of apoptosis in duct obstruction-induced pancreatic involution in rats.
AB  - It has been recognized in mammals that after pancreatic duct obstruction, acinar
      cells progressively disappear and pancreatic islets are preserved. Previous
      studies by electron microscopy have suggested the involvement of apoptosis in
      acinar cell deletion. In the present study, we employed molecular biological
      methods and investigated whether acinar cell deletion is due to apoptosis. In
      male Sprague-Dawley rats, pancreatic duct ligation was performed through a left
      paramedian incision. Pancreatic tissue was studied at each of the following
      intervals after ligation: 3, 6, 12, 18, and 24 h and 2, 3, 5, and 7 days. DNA
      fragmentation was determined by in situ labeling of DNA strand breaks on tissue
      sections [fluorescein-labeled terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labeling method (TUNEL)] and by electrophoretic detection of the
      fragments of extracted DNA. Tissue sections were also examined by
      hematoxylin/eosin staining and immunohistochemical staining of insulin.
      Pancreatic duct ligation induced acinar cell deletion by day 5. Pancreatic tissue
      from control rats demonstrated no TUNEL-positive nuclei. In contrast, acinar
      cells from rats 12 h to 5 days after duct ligation showed TUNEL-positive nuclei.
      The number of TUNEL-positive nuclei was maximum 2 days after duct ligation.
      Electrophoresis showed DNA fragmentation after duct ligation. Control rats showed
      a genomic DNA pattern. Islets were preserved throughout the experimental period
      in duct-ligated rats and control rats. The results suggest that apoptosis may be
      the dominant form of acinar cell death in the rat pancreatic duct ligation model.

PMID- 8981507
TI  - Modulation of pancreatic secretion of individual digestive enzymes in octreotide
      (SMS 201-995)-infused rats.
AB  - We demonstrated previously that pancreatic secretion of individual enzymes is
      specifically regulated (1). In the present study, we investigated and defined
      contributing roles of cholinergic and cholecystokinin tones to the specific
      regulation of rat pancreatic secretion of digestive enzymes. Animals were
      provided with pancreatic, biliary, duodenal, and jugular vein cannulas allowing
      separate drainage of bile and pure pancreatic juice, as well as intravenous
      infusions of MK329 or atropine sulfate along with SMS 201-995 (SMS). Rats kept in
      restraint cages were divided into four groups. The first rat group was infused
      with 5 micrograms kg-1 h-1 SMS alone; the second group was infused with a mixture
      of SMS and MK329 (5 micrograms kg-1 h-1:0.5 mg kg-1 h-1); the third group
      received a mixture of SMS and atropine (5 micrograms kg-1 h-1); and rats in the
      fourth group were administrated a mixture of SMS, MK329, and atropine (5
      micrograms kg-1 h-1:0.5 mg kg-1:100 micrograms kg-1 h-1). Food, but not water,
      was denied rats 10 h before the experiment and throughout the 6-h experimental
      period. During the experiment, pancreatic juice was continuously collected every
      15 min from each rat, and a 15-microliter aliquot of the pancreatic juice sample
      was removed for total protein, amylase, lipase, trypsinogen, chymotrypsinogen,
      and proelastase assays. Pancreatic juice previously collected from a donor rat
      was mixed with the fresh bile and the mixture was recirculated into the duodenum.
      The secretory patterns over the 6-h experimental period showed that during the
      first hour of drug infusion, MK329 alone did not alter the SMS-induced inhibitory
      process of total protein and amylase, trypsinogen, and proelastase secretion, and
      there was no marked change in total protein and enzyme outputs. Adding atropine
      to SMS did not alter the secretory pattern during the first hour of drug
      infusion, but a significantly greater decrease in protein and enzymes outputs
      occurred. Correlations between paired enzyme outputs greatly increased with SMS
      alone, but some changed when either MK329 or atropine was infused along with SMS.
      When all drugs were infused together, enzyme outputs became strongly correlated.
      These results suggest that under fasting conditions, somatostatin and atropine
      can neutralize basal pancreatic enzyme outputs, leading to a constitutive type of
      secretion characterized by parallel secretion of the digestive enzymes.
      Furthermore, it is proposed that under basal secretion conditions, acetylcholine
      and cholecystokinin reaching the pancreatic acinar cells may act to dissociate
      pancreatic secretion of individual digestive enzymes originating from
      heterogeneous secretory granules.

PMID- 8981508
TI  - Postnatal sequential changes in islet morphology and insulin secretion of normal
      hamsters.
AB  - We have studied the postnatal development of the endocrine pancreas from normal
      female Syrian golden hamsters 1, 8, and 24 weeks of age. The observations were
      made by (a) analysis of insulin secretion in response to glucose using isolated
      pancreatic islets and (b) identification and quantitation of insulin-, glucagon-,
      somatostatin-, and pancreatic polypeptide-secreting cells. Glucose-induced
      insulin secretion showed typical dose-response curves. However, whereas in 24
      week-old animals maximal secretion was already present with 8 mM glucose, in
      younger hamsters such a response was attained only with 20 mM glucose. The volume
      density of the endocrine pancreas and the number of islets were increased in 1
      week-old hamsters compared to the older animals. The islet volume average in 8
      week-old hamsters was almost three times higher than that measured in 1-week-old
      animals. However, the proportion and size of each cell type in the islets did not
      present significant differences among the groups studied. Our results show that,
      in hamsters, the endocrine pancreas reaches the adult general characteristics
      late after birth. Furthermore, the definite morphological pattern is attained far
      earlier than the secretory response. These observations provide basic information
      for further studies regarding the mechanisms and factors that control both the
      growth and the differentiation of endocrine cell populations as well as glucose
      induced insulin secretion in a simple experimental model.

PMID- 8981509
TI  - Induction of a glucose-dependent insulin secretory response by the
      nonmetabolizable amino acid alpha-aminoisobutyric acid.
AB  - The effects of the nonmetabolizable amino acid alpha-aminoisobutyric acid (AIB)
      on insulin release were evaluated using beta cell-rich pancreatic islets from
      ob/ob mice. Both AIB and L-alanine promptly induced transient insulin release
      during column perifusion of islet cells. The secretory response was dependent on
      an elevated level of glucose and effectively suppressed by removal of Na+. The
      insulin release elicited by AIB fulfilled the criteria of a physiological event
      in being suppressed by clonidine or lowering of the temperature to 22 degrees C.
      AIB effectively promoted the increase in sodium (total as well as ionized
      cytoplasmic) obtained with ouabain blockage of the Na/K pump. When added to a
      medium containing 11 mM glucose, AIB altered cytoplasmic Ca2+ in terms of both an
      initial transitory rise and transformation of existing oscillations into a
      sustained elevation. It is concluded that amino acids can stimulate insulin
      release from mature beta cells by virtue of being cotransported with Na+.

PMID- 8981510
TI  - Beta-cell function abnormalities in islets from an adult subject with
      nesidioblastosis and autoantibodies against the islet cells.
AB  - Human islets from an adult subject with nesidioblastosis were isolated and used
      to perform in vitro studies. Isolated nesidioblastotic islets showed an increased
      basal rate of insulin secretion (nesidioblastotic islets, 81.3 +/- 6.4 vs.
      control islets, from cadaveric organ normal donors, 10.2 +/- 0.9 microU/islet/90
      min) without any further release with increasing glucose concentration. In
      addition, islets isolated from the pancreas with nesidioblastosis contained more
      insulin than control islets, 1,547.0 +/- 128.7 vs. 935.0 +/- 51.7 microU/islet,
      and the levels of insulin mRNA were also higher than those measured in controls.
      Interestingly, the serum of the subject with nesidioblastosis contained
      autoantibodies that stained brightly and selectively a population of islet cells
      whose distribution coincided with that expected of alpha cells. In summary,
      pancreatic islets in nesidioblastosis display beta-cell functional abnormalities.
      Moreover, the finding of antibodies against islet cells is a common feature in
      the serum of nesidioblastotic subjects; nevertheless, their pathological
      significance warrants further investigation.

PMID- 8981511
TI  - Intraduodenal free fatty acids rather than triglycerides are responsible for the
      release of CCK in humans.
AB  - Exocrine pancreas from different species behaves differently in response to the
      presence of intact or digested nutrients in the duodenum. A failure of
      cholecystokinin (CCK) release after a meal has been shown among patients with
      exocrine pancreatic insufficiency. This abnormality could be restored by the
      administration of pancreatic extracts, suggesting that digested rather than
      intact nutrients are responsible for the release of CCK and subsequently
      gallbladder contraction in humans. The aim of this study was to determine the
      specific role of different lipidic stimuli in humans. Seven male patients (mean
      age, 52 years) with pancreatic insufficiency secondary to chronic pancreatitis
      were selected. Pancreatic insufficiency was considered severe in five of them
      (lipase output, < 1,000 IU/min) and moderate in another two (lipase output, >
      1,000 and < 2,300 IU/min). Plasma CCK (by bioassay), gallbladder contraction (by
      ultrasound), and enzyme output (chymotrypsin) in response to duodenal
      administration of either oleic acid as free fatty acids or 20% Intralipid as
      triglycerides were measured in each patient with at least a 48-h interval between
      each test. In all these patients with pancreatic insufficiency, duodenal
      perfusion of free fatty acids generated a more pronounced (91 +/- 11 vs. 49 +/-
      21 pM) and faster (15 vs. 30 min) (p < 0.05) CCK release than triglycerides.
      Furthermore, gallbladder contraction was more efficient when free fatty acids
      instead of triglycerides were administered in the duodenum (86 +/- 5 vs. 69 +/-
      4%) at 10 min (p < 0.05) and (73 +/- 8 vs. 51 +/- 5%) at 15 min (p < 0.03). Among
      patients with measurable residual pancreatic function, enzyme outputs were shown
      to be higher during free fatty acid than triglyceride perfusion. In humans, free
      fatty acids rather than triglycerides, when present in the duodenum, stimulate
      CCK release and gallbladder contraction. In patients with moderate pancreatic
      insufficiency this phenomenon may increase residual enzymatic secretion. These
      results allow us to encourage the development of enzymatic preparations as acid
      resistant lipases that cause a fast release of free fatty acids in the duodenum.

PMID- 8981512
TI  - Cholinergic transmission in pancreatic ganglia of the cat.
AB  - Although there is considerable evidence indicating the existence of important
      cholinergic neural regulation of pancreatic function, very little is known about
      the action of acetylcholine on pancreatic ganglion neurons. The present study was
      undertaken to determine the effect of pressure microejection of acetylcholine and
      muscarine on ganglion cell excitability of the cat pancreas. Recordings were made
      in vitro from ganglion neurons located in the head region of the pancreas.
      Acetylcholine evoked a fast- and a slow-developing membrane depolarization in the
      majority of neurons tested. A decrease in membrane input resistance accompanied
      the fast depolarizing response, whereas an increase in input resistance
      accompanied the slow depolarizing response. The fast response was mimicked by 1,1
      dimethyl-4-phenylpiperazinium iodide and nicotine and antagonized by
      hexamethonium. The slow depolarizing response was mimicked by muscarine and
      antagonized by atropine and pirenzepine. The dependence of the slow
      depolarization on extracellular K+ and the distinct voltage dependence of the
      slow depolarization suggest that activation of muscarinic receptors was due to
      inactivation of IM. The slow excitatory postsynaptic potential and associated
      increase in excitability evoked by repetitive nerve stimulation was partially
      cholinergic dependent in the majority of neurons tested. It was concluded that
      cholinergic transmission in cat pancreatic ganglia involves nicotinic and M1
      receptors that mediate fast and slow synaptic transmission, respectively, and
      that activation of M1 receptors modifies the output firing frequency.

PMID- 8981513
TI  - Epidermal growth factor induces cell proliferation in mouse pancreas and salivary
      glands.
AB  - Epidermal growth factor (EGF) is a mitogenic stimulus in many tissues and occurs
      in large amounts in the pancreas and salivary glands. Whether EGF is mitogenic in
      the pancreas is controversial, and the EGF effect has not been studied in the
      salivary glands. Therefore, the aim of the present study was to investigate the
      possible effects on the pancreas and parotid and submandibular glands at
      different time intervals after exogenous EGF administration. Human recombinant
      EGF was infused subcutaneously by osmotic minipumps in three groups of mice (for
      1, 3, and 7 days, respectively) at a dosage of 10 micrograms/kg/h (1.6
      mumol/kg/h). Tritiated thymidine was infused intraperitoneally by osmotic
      minipumps for the same time periods, but only for the last 3 days in the 7-day
      group. After 1 day the pancreas increased in weight and the increase persisted
      throughout the study. No effect was seen on the parotid or submandibular gland
      wet weight. A slight transient increase in pancreas protein content was observed,
      whereas amylase content was unaffected. The labeling index of serous and ductal
      cells in the parotid gland increased from the third day. After 7 days, all cell
      types studied in the pancreas and parotid and submandibular glands were in a
      hyperproliferative state. The results show that EGF evoked a strong proliferative
      response on all cell types studied in the pancreas and parotid and submandibular
      glands.

PMID- 8981514
TI  - Squamous cell carcinoma of the pancreas accompanied by mucinous
      cystadenocarcinoma: a case report of an unusual association.

PMID- 8981515
TI  - GP-2 is the major ATP-binding protein of pig pancreatic zymogen granule
      membranes.

PMID- 8981516
TI  - Role of the cholecystokinin (CCK)-A receptor in pancreatic growth in rats during
      the suckling period: a study in a naturally occurring CCK-A receptor gene
      "knockout" rat.

PMID- 8981517
TI  - Pancreatitis and the risk of pancreatic cancer.

PMID- 8981518
TI  - A large step in the treatment of peritonitis in peritoneal dialysis patients.

PMID- 8981520
TI  - Should growth hormone be used in dialysis-dependent children?

PMID- 8981521
TI  - Is long-term technique survival on continuous ambulatory peritoneal dialysis
      possible?

PMID- 8981522
TI  - A message to nurses from the nurse council member.

PMID- 8981523
TI  - Peritoneal dialysis-related peritonitis treatment recommendations: 1996 update.
AB  - The recommendations provided in this document represent a distillation of various
      experiences, as well as data obtained from published studies in the setting of
      substantial changes in antibiotic sensitivity. It is hoped that this revised
      compilation will provide a basis upon which future developments and advances can
      be made in the therapeutic approach to infectious complications of peritoneal
      dialysis.

PMID- 8981524
TI  - Surfactant protein A and lamellar bodies: a homologous secretory function of
      peritoneum, synovium, and lung.
AB  - OBJECTIVE: To review recent discoveries on the existence of lamellar body
      secreting cells in extrapulmonary sites with respect to their constitution as a
      previously unrecognized coherent biological system and to evaluate the role of
      mesothelial research in peritoneal dialysis in initiating this new field of
      medical research. DATA SOURCES: Studies in the literature on the production and
      metabolism of pulmonary surfactant with respect to lamellar bodies and surfactant
      protein A (SP-A). Published investigations on the identification of lamellar
      bodies and SP-A in extrapulmonary sites and their possible role in systemic
      expression of autoimmune disorders. RESULTS: It is now established that lamellar
      bodies of identical periodicity and ultrastructural geometry are present in lung
      (type II pneumocytes), serosal mesothelium (peritoneum, pleura, and pericardium),
      and joints (type A and type B synoviocytes). Not only pulmonary lamellar bodies
      but those at extrapulmonary sites are found in association with SP-A, while SP-A
      or SP-A-like proteins are present in measurable quantities in normal serosal
      fluids. These findings have disclosed totally new avenues of research into
      multisystem disorders, where for the first time an organelle and associated
      protein provide a link between diverse tissues affected by rheumatoid disease.
      Evidence of shared epitopes between SP-A and mycobacterial 65-kD heat shock
      protein indicates a possible etiologic mechanism. CONCLUSIONS: A hitherto
      ultrastructurally hidden system of lamellar body secretion is now being revealed
      as a major biological system which appears to subserve surfactant, lubricant,
      surface protection, and sealant functions in body surfaces and tissue interfaces.
      This new frontier was born out of investigations into the hitherto neglected
      biology of peritoneal mesothelium, research which was vital for advancing the
      therapy of peritoneal dialysis and for preservation of the dialyzing membrane.

PMID- 8981525
TI  - Long-term continuous ambulatory peritoneal dialysis reduces the expression of
      CD11b, CD14, CD16, and CD64 on peritoneal macrophages.
AB  - OBJECTIVE: To characterize phenotypically the macrophages from nocturnal
      peritoneal effluent (NPE) in patients on continuous ambulatory peritoneal
      dialysis (CAPD), and to determine the influence of the length of this therapy on
      macrophage (M phi) function. DESIGN: Cross-sectional descriptive study. PATIENTS:
      Fifty-five patients on CAPD who were classified into short-, medium-, and long
      term groups according to their time on CAPD. Peritoneal macrophages (PM phi) were
      also characterized in 7 patients at the time of catheter placement, and there
      were 13 normal controls. INTERVENTIONS: Macrophages were collected from NPE by
      centrifugation. MEASUREMENTS: Membrane receptor expression was evaluated by flow
      cytometry analysis. RESULTS: Flow cytometry analysis revealed that the expression
      of CD11b, CD16, CD64, and CD14 on NPE macrophages was reduced during the course
      of CAPD treatment, reaching levels which represented a 40%-50% reduction of the
      cell surface expression detected at the start of the treatment or on normal
      control macrophages. Both normal and CAPD PM phi expressed CD4, CD69, and CD71
      very weakly and lacked CD25. No changes in HLA-DR or in other adhesion protein
      (CD11a, CD11c, CD18, CD54) expression were detected, and levels were similar in
      both patients and normal controls. CONCLUSION: Our results show that long-term
      CAPD might affect Fc gamma receptor-mediated phagocytosis by reducing the
      expression of CD16, CD64, and CD11b. Lower CD11b and CD14 expression would also
      impair PM phi adhesion to mesothelial structures.

PMID- 8981526
TI  - 24-hour dialysate collection for determination of peritoneal membrane transport
      characteristics: longitudinal follow-up data for the dialysis adequacy and
      transport test (DATT).
AB  - OBJECTIVE: To determine the ability of the dialysis adequacy and transport test
      (DATT) to monitor changes in peritoneal transport characteristics over time.
      SETTING: University-based peritoneal dialysis program. PATIENTS: One hundred
      patients on continuous ambulatory peritoneal dialysis who underwent 226
      simultaneous DATTs and peritoneal equilibration tests (PET). METHODS:
      Retrospective analysis of DATT and PET data. RESULTS: The mean 24-hour dialysate
      to-plasma creatinine (cr) concentration ratio (D/P cr) from the DATT was 0.70 +/-
      0.10, and the mean four-hour D/P cr from the PET was 0.68 +/- 0.10. The
      correlation coefficient between the four-hour and 24-hour D/P cr was 0.81, and
      the standard error of estimate was 0.065. The mean (+/- SD) difference between
      the four-hour and 24-hour D/P cr was 0.023 +/- 0.061. Fifty-eight patients had
      two or more sequential DATTs and PETs. For these 94 sets of sequential DATTs and
      PETs, the mean (+/- SD) difference between the change in the four-hour D/P cr and
      the change in the 24-hour D/P cr was 0.020 +/- 0.024, and the standard error of
      estimate was 0.064. In 17 patients a change in dwell volume from 2.0 L to 2.5 L
      occurred between the first and second measures of peritoneal membrane transport
      characteristics. The mean (+/- SD) difference between the change in the four-hour
      D/P cr and the change in the 24-hour D/P cr was 0.036 +/- 0.055, and the standard
      error of estimate was 0.087. CONCLUSION: The DATT can be used to monitor for
      changes in peritoneal transport over time. It should not be used in patients
      receiving cycler therapy or in patients whose dwell times and dextrose
      concentrations vary markedly from day to day.

PMID- 8981527
TI  - Efficacy of recombinant human erythropoietin administered subcutaneously to CAPD
      patients once weekly.
AB  - OBJECTIVE: The purpose of the present study was to compare the dosage
      requirements of recombinant human erythropoletin (rHuEPO) administered
      subcutaneously (SC) either one or three times weekly. DESIGN: A randomized,
      prospective study. SETTING: The patients were recruited from two university
      hospitals and five county hospitals. PATIENTS: Thirty-three anemic patients on
      continuous ambulatory peritoneal dialysis (CAPD) treatment for end-stage renal
      failure completed the study. INTERVENTIONS: Initially, all were treated with
      rHuEPO SC three times a week until hemoglobin blood levels (Hb) remained constant
      between 105 and 121 g/L for three months. Following randomization, 17 patients
      continued the same treatment schedule (group A), while 16 patients received the
      same dose, but administered only once weekly for three months (group B). MAIN
      OUTCOME MEASURES: The Hb levels and rHuEPO doses at the start and at the end of
      the three-month study period. RESULTS: In group A the median Hb at randomization
      was 118 g/L (109-119) (25-75 percentiles) and, after three months, was 113 g/L
      (106-119) (p = 0.13), while in group B the median Hb was 114 g/L (108-119) and
      114 g/L (106-120), respectively (p = 0.50). In group A the weekly dose of rHuEPO
      remained virtually unchanged during the study period, 65 (55-86) and 66.3 (55-95)
      U/kg/week, respectively, while in group B it was increased from 60.2 (46-88) to
      77 (60-90) U/kg/week. The 22% increase (p = 0.03) took place during the last two
      weeks. CONCLUSIONS: Our findings indicate that a once-weekly SC dosing regimen of
      rHuEPO in anemic CAPD patients was equally effective in maintaining a stable
      hemoglobin level as a thrice-weekly dosing regimen.

PMID- 8981528
TI  - L-cysteine improves growth of human peritoneal mesothelial cells in vitro.
AB  - OBJECTIVE: To improve the growth characteristics of human peritoneal mesothelial
      cells (HPMC). DESIGN: The effect of commonly used agents, L-cysteine and
      epidermal growth factor (EGF), added individually ("single") or mixed with
      hydrocortisone and apo-transferrin ("admixture") in the culture medium (M199) on
      cultured HPMC, was investigated. METHODS: Growth agents were added to M199 medium
      along with 2% fetal bovine serum and L-glutamine. Growth was determined by the
      analysis of thymidine ([methyl-3H] thymidine) incorporation into deoxyribonucleic
      acid, total cell protein, and by cell counts. Morphology was assessed by phase
      contrast light microscopy and scanning electron microscopy. RESULTS: HPMC exposed
      to L-cysteine 0.25 x 10(-3) mol/L (30 micrograms/mL) exhibited significantly
      improved attachment and growth. Attached cells appeared flat and well spread out
      shortly after seeding, and produced a tight polygonal monolayer in 14 days, in
      contrast to the growth of HPMC in control M199 medium, which failed to reach
      confluence. After an initial lag period in cell growth, EGF (0.01 microgram/mL)
      produced a greater increase in cell growth than L-cysteine did; however, this was
      associated with changes in HPMC morphology. During the growth period (14 days),
      EGF-stimulated HPMC appeared distorted and irregular compared to L-cysteine
      treated cells, which had the characteristic tight "cobblestone" appearance.
      CONCLUSION: L-cysteine improved cell attachment with preservation of the
      characteristic morphology of HPMC. Epidermal growth factor improved cell growth
      but produced changes in morphology. The addition of L-cysteine to the culture
      medium has an important cell growth enhancement role due to the improved cell
      attachment and cell viability.

PMID- 8981529
TI  - Interleukin-10, interferon gamma, interleukin-2, and soluble interleukin-2
      receptor alpha detected during peritonitis in the dialysate and serum of patients
      on continuous ambulatory peritoneal dialysis.
AB  - OBJECTIVE: To analyze interleukin (IL)-10, interferon gamma (IFN-gamma), IL-2,
      and soluble IL-2 receptor alpha (sIL-2R alpha) in the dialysate and serum of
      patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN AND
      PATIENTS: Samples from dialysate bags were collected during the initial month of
      dialysis. During peritonitis, samples were collected from the first three bags on
      the day of admittance to the hospital and from the night bags on days 3 and 10.
      Serum samples were drawn on days 1 and 10. RESULTS: IL-10 was detected in all
      dialysate samples except one on the first day of infection, with a peak median
      level of 50 pg/mL and a slow decrease thereafter. In serum the median levels
      never exceeded detectable levels. Patients infected with Escherichia coli or
      Staphylococcus aureus had higher IL-10 levels in dialysate on day 3 as compared
      to the remaining patients (p < 0.05). If the catheter had to be drawn, because of
      persistent cloudy dialysate, the IL-10 levels remained elevated for a longer time
      (p < 0.05). IFN-gamma and IL-2 were detected only in the dialysate of patients
      infected with either S. aureus or S. epidermidis. Only one serum sample showed
      increased IFN-gamma. SIL-2R alpha was found in all the serum and dialysis samples
      from the first day of infection. Contrary to the analyzed cytokines, the receptor
      showed severalfold higher levels in serum as compared to the dialysate. During
      the infection the receptor levels in the dialysate increased, while they remained
      stationary in the serum, indicating a local production. CONCLUSION: This is the
      first time IL-10 has been demonstrated in the dialysate during peritonitis in
      CAPD patients. In view of its role as a suppressor of the immune and inflammatory
      responses, it is a potentially important observation, which might have clinical
      implications in the future.

PMID- 8981530
TI  - Abdominal cocoon: an animal model for a complication of peritoneal dialysis.
AB  - OBJECTIVE: The purpose of this work was to develop an animal model of sclerosing
      encapsulating peritonitis, a complication of continuous ambulatory peritoneal
      dialysis in which the intestines are conglomerated into an ovoid cocoonlike
      structure. DESIGN: Toward this end, rats were injected with a chemical irritant
      (household bleach) intraperitoneally. One week later, before the resultant
      peritonitis could cause adhesions, 10 or 25 mL of fresh whole rat blood was
      injected into the peritoneal cavity. Two weeks later, the effect of the
      treatments was evaluated by macroscopic and microscopic study. RESULTS: The
      irritant caused a chemical peritonitis. The subsequently injected blood clotted
      on the surfaces of the inflamed intestines, and contraction of the clot
      (syneresis) was responsible for bringing the intestinal loops together. This
      conglomeration was made permanent by the fibrosis evoked by the chemical
      peritonitis. The end result was an ovoid encapsulated mass of intestines and
      other viscera. CONCLUSION: An animal model for an abdominal cocoon has been
      produced. It can be used for studies of the pathogenesis and prevention of this
      complication of peritoneal dialysis.

PMID- 8981531
TI  - Body surface area limitations in achieving adequate therapy in peritoneal
      dialysis patients.
AB  - OBJECTIVE: To estimate the maximal body surface area (BSA) at which anuric
      chronic peritoneal dialysis patients can achieve adequate peritoneal dialysis
      using a variety of continuous ambulatory peritoneal dialysis (CAPD) and cycler
      regimens. Adequate dialysis was defined as a creatinine clearance of either 60
      L/week/1.73 m2 or 70 L/ week/1.73 m2. DESIGN: Calculation of daily peritoneal
      creatinine clearances using standard formulas. For CAPD patients, creatinine
      clearance was calculated using published values for dialysate-to-plasma ratios
      for creatinine (D/P cr) measured over a 24-hour period and assuming a daily
      ultrafiltration rate of 1.5 to 2.0 L/day. For cycler patients, creatinine
      clearance was calculated for both one- and two-hour dwell volumes, using
      published values for D/P cr from the peritoneal equilibration test and assuming a
      daily ultrafiltration rate of 2.0 L/day. All clearances were corrected to a
      normalized body surface area of 1.73 m2. RESULTS: For CAPD patients, 2-L dwell
      volumes can provide a weekly creatinine clearance of 60 L/week/1.73 m2 in
      patients with BSA < 1.45 m2 in the high transporter group and with BSA < 1.2 m2
      in the low-average transporter group. Increasing dwell volume from 2.0 to 2.5 L
      increases these BSA limits in the four transport groups by 0.2-0.3 m2. Cycler
      therapy is not a viable option for patients in the low transporter group, and
      this therapy can achieve adequate creatinine clearances in patients in the low
      average transport group only with large dwell volumes and in patients with BSA <
      1.55 m2. However, in the high-average and high transporter groups, cycler therapy
      provides for superior creatinine clearances compared to CAPD patients using
      similar dwell volumes. CONCLUSIONS: Adequate creatinine clearances in anuric
      patients are most likely to be achieved in patients with BSA > 2.0 m2 if they
      have high-average or high transport characteristics and are receiving cycler
      therapy with large dwell volumes and at least one daytime dwell. However,
      adequate creatinine clearances may be difficult to achieve in anuric patients who
      have a large BSA and a low or low-average transport type, regardless of
      peritoneal dialysis modality. These patients should be considered for either high
      dose peritoneal dialysis (multiple daytime and nighttime exchanges) or
      hemodialysis therapy.

PMID- 8981532
TI  - A new self-locating peritoneal catheter.
AB  - OBJECTIVE: Peritoneal catheters often become dislocated, and this may lead to
      malfunction. Since it is not usually possible to bring them back into their
      correct position, they must be replaced. With the aim of preventing this
      complication, we designed a new catheter. DESIGN: The new catheter has the same
      form as the Tenckhoff catheter except for a small increase in external diameter
      of the last 2 cm, made possible by the high specific weight of a small 12-g
      tungsten cylinder incorporated in the Silastic at the abdominal end. The new
      catheter may be inserted by a percutaneous technique. SETTING: University
      hospitals of Siena and Perugia, Italy. PATIENTS: In the last three years, 32 of
      these catheters have been implanted for a total experience of 468 patient-months.
      Their position was checked on insertion and every two months thereafter by
      radiography; 26 Tenckhoff catheters (415 patient-months) were studied at the same
      time. Insertion was performed surgically and by a percutaneous method. The
      frequency of cuff extrusion, exit-site infections, leakage, and peritoneal
      infection were noted, together with peritoneal function, which was evaluated by
      KT/V and weekly creatinine clearance one month after catheter insertion; the
      tests were repeated when dislocation occurred and at the end of the trial.
      RESULTS: No dislocations occurred with the self-locating catheters, whereas nine
      dislocations occurred in control patients (p = 0.0003). There were no significant
      differences with respect to controls for cuff extrusion, exit-site infections,
      leakage, peritoneal infection, and peritoneal function. CONCLUSIONS: The presence
      of a small weight at the catheter up prevents displacement completely, keeping
      the intraperitoneal part of the catheter in place.

PMID- 8981533
TI  - The study of outcomes for CAPD versus hemodialysis patients.
AB  - OBJECTIVE: To discuss potential reasons for reported differences in the results
      of several recent studies comparing mortality risk among continuous ambulatory
      peritoneal dialysis (CAPD) and hemodialysis patients, and to assess the role of
      statistical methods and study design. DATA SOURCES: Recent published reports
      comparing mortality risk among patients treated with CAPD and hemodialysis.
      CONCLUSIONS: Differences in study design, study populations, sample size, data
      collection, and availability of data likely account in part for the differences
      in available study results. The Cox model is a valuable tool, particularly for
      observational studies. Observed outcome differences for CAPD and hemodialysis
      patients may be due to either the dialytic modality itself or other factors such
      as differences in patient selection, practice patterns, dialysis dose, patient
      compliance, etc. Relative mortality rates for hemodialysis and CAPD patients may
      vary by country, as these factors may differ internationally. A randomized
      clinical trial is necessary to best determine the effect of the modality itself.

PMID- 8981534
TI  - Use of amino acid peritoneal dialysate for one year in a child on CCPD.

PMID- 8981535
TI  - A cluster of gram-negative peritonitis episodes associated with reuse of
      HomeChoice cycler cassettes and drain lines.

PMID- 8981536
TI  - Gram-negative peritonitis in peritoneal dialysis: improved outcome with
      intraperitoneal ceftazidime.

PMID- 8981537
TI  - Correction of outflow obstruction with the use of sennosides in CAPD patients.

PMID- 8981538
TI  - Hemoperitoneum in peritoneal dialysis secondary to retroperitoneal hematoma.

PMID- 8981539
TI  - IgM antibodies to hepatitis C virus.

PMID- 8981541
TI  - Peritoneal dialysis in the year 2010: we should begin to think in terms of the
      KT/V of the spiritual parts of technology.

PMID- 8981540
TI  - Intraperitoneal iron-dextran as a potential route of iron therapy in CAPD
      patients.

PMID- 8981542
TI  - Pasteurella multocida peritonitis: are peritoneal dialysis patients on cyclers at
      increased risk?

PMID- 8981543
TI  - The treatment of octogenarians.

PMID- 8981544
TI  - Hemoperitoneum occurs in over half of menstruating women on peritoneal dialysis.

PMID- 8981545
TI  - Low prevalence of vancomycin-resistant Enterococcus in dialysis outpatients with
      a history of vancomycin use.

PMID- 8981547
TI  - Literature. September-October 1996.

PMID- 8981546
TI  - Hypokalemia in peritoneal dialysis patients.

PMID- 8981548
TI  - Regulatory status of medicinal products for human beings in the European Union.
      The role of generic products.
AB  - In this paper the definition and classification of medicinal products are
      discussed. Medicinal products from a regulatory and administrative point of view
      can be classified as: proprietary medicinal products (copy and new drugs), other
      medicinal products of industrial origin and, magistral and officinal formulas
      prepared by pharmacies (also called 'generic products'). The term 'generic
      product' becomes relevant only when the economic impact of medicinal products is
      considered. The formal characteristics of medicaments, as well as the different
      possible producers (industry or pharmacy) will be considered also in relation to
      the interchangeability of medicaments and the role of generic products.

PMID- 8981549
TI  - Pharmacology of the hypoglycaemic sulphonylurea gliquidone. III. Conformational
      analysis.
AB  - The hypoglycaemic sulphonylurea gliquidone was found, by conformation analysis,
      to display a U-shaped configuration, with hydrophobic cycles placed at the
      extremity of each branch and a peptidic bond placed at the bottom of the U. This
      configuration is similar to that recently observed with the hypoglycaemic
      sulphonylureas glimepiride and glibenclamide and non-sulphonylurea hypoglycaemic
      agents of the meglitinide family, such as S3075, repaglinide, A-4166 and KAD
      1229. The identification of a conformation common to these various hypoglycaemic
      drugs may provide an imprint of their binding site at the level of the B-cell
      sulphonylurea receptor.

PMID- 8981550
TI  - Nadolol-glibenclamide interaction: relevance to carbohydrate metabolism in
      hyperglycaemic rats.
AB  - In the present study, hyperglycaemia was induced by intraperitoneal injection of
      streptozotocin (65 mg/kg). Treatment with glibenclamide (GB) in a dose of 0.45 or
      0.9 mg/kg significantly decreased plasma glucose level in a dose-related manner.
      Administration of nadolol (ND) in a dose of 5 or 10 mg/kg did not affect plasma
      glucose level. Combined administration of ND (10 mg/kg) with GB (0.45 or 0.9
      mg/kg) potentiated the hypoglycaemic effect of GB, an effect prominent 4 hours
      post-treatment. In relevance to the effect of ND and GB interactions towards
      other aspects of carbohydrate metabolism, co-administration of the two drugs [ND
      (10 mg/kg) + GB (0.9 mg/kg)] failed to alter the increase in plasma insulin level
      and the decrease in blood pyruvate and lactate levels induced by GB alone.
      Concerning liver glycogen, concurrent administration of the two drugs showed a
      synergistic effect upon its content (257%), while it was 186% for GB treatment,
      and 179% for ND alone compared to the hyperglycaemic control value. The data
      revealed that ND potentiates the hypoglycaemic effect of GB, so it is very
      important to consider this potentiation when the usage of the combined drug
      regimens is recommended.

PMID- 8981551
TI  - Thimerosal attenuates ischaemia-reperfusion arrhythmias in rats: no modification
      by anti-ischaemic agent trimetazidine or endothelin receptor antagonist bosentan.
AB  - The effects of acyl-coenzyme a: lysolecithin acyltransferase (LAT) inhibitor
      thimerosal (20, 30 and 40 mg kg-1), anti-ischaemic and free radical scavenging
      drug trimetazidine (10 mg kg-1) and endothelin ETA-ETB receptor blocker bosentan
      [30 mg kg-1) were investigated in an anaesthetized rat model of coronary artery
      ligation (7 min) and release (7 min) induced myocardial ischaemia-reperfusion
      arrhythmias. Neither of the drugs produced significant effects on blood pressure
      except thimerosal which induced a transient fall lasting 5-8 min. The total
      number of ectopic beats during occlusion (controls 141.8 +/- 73.5, n = 12) and
      reperfusion (controls 1151.1 +/- 199.1, n = 10) was not modified by either
      trimetazidine (occlusion 452.5 +/- 128.6, n = 10; reperfusion 1002.0 +/- 198.4, n
      = 6) or bosentan (occlusion 431.2 +/- 112.8, n = 10; reperfusion 1530.7 +/-
      296.8, n = 9) while thimerosal attenuated them (occlusion 50.2 +/- 14.9, n = 10,
      P < 0.01 vs controls; reperfusion 345.1 +/- 83.8, n = 8, P < 0.01 vs controls).
      The durations (in seconds) of ventricular tachycardia (occlusion 33.9 +/- 6.1, n
      = 12; reperfusion 94.2 +/- 18.1, n = 10) were also shortened by thimerosal
      (occlusion 2.6 +/- 1.0, n = 10, P < 0.01; reperfusion 28.5 +/- 7.8, n = 8, P <
      0.01) while trimetazidine or bosentan did not significantly modify them. The
      incidences of ventricular fibrillation or mortality were not significantly
      modified by either of the drugs. Besides the lack of any effect of trimetazidine,
      we conclude that endogenous endothelin has no pathophysiological significance in
      this experimental model while LAT inhibition does.

PMID- 8981553
TI  - Effect of 2-methyltaurine and its enantiomers on arterial blood pressure.
AB  - Taurine has been shown to exert many biological effects. Among them, the ability
      of this amino acid to induce a reduction of arterial blood pressure, when
      administered intracerebroventricularly (i.c.v.) to mammals, has been established
      since a long time ago. To gain further information on the structure-activity
      requirements for taurine's hypotensive effect, the synthesis of 2-methyltaurine
      (2-aminopropanesulphonic acid) and the asymmetric synthesis of its enantiomers
      were performed; the enantiomeric purity of (R)- and (S)-2-methyltaurine was
      assayed by differential scanning calorimetry (DSC) and HPLC. The findings here
      reported show that the hypotensive effect elicited by the i.c.v. administration
      of racemate is mainly due to the (S)-enantiomer. The specificity of this effect
      was proved by the ability of the taurine antagonist TAG (6-aminomethyl-4H-3
      methyl-1,2,4-benzothiadiazine 1,1-dioxide) to prevent it.

PMID- 8981552
TI  - Protection of rat heart from ischaemia-reperfusion injury by the 21-aminosteroid
      U-74389G.
AB  - In ischaemia-reperfusion syndromes lipid peroxidation appears an important factor
      contributing to tissue damage. The 21-aminosteroids (lazaroids) exhibit
      beneficial effects in various pathological conditions, especially in post
      traumatic lesions of the central nervous system, where a peroxidative injury
      seems to be involved. The aim of our study was to ascertain if one of these
      compounds, U-74389G, plays a significant role in protecting heart muscle from
      ischaemia-reperfusion damage. Rat hearts used for heterotopic transplantation
      represented the experimental model in this investigation. Animals (Wistar rats
      weighing 200-250 g) were divided into five groups: controls, untreated and
      treated donors, untreated and treated recipients. Donors were anaesthetized and
      heparinized, and the heart was excised through a bilateral thoracotomy, arrested
      with St Thomas solution and stored in cold saline for 2 hours. For the recipient
      preparation, a modified Ono's technique was used, and heart reimplantation was
      performed with a termino-lateral aorto-aortic anasthomosis and a termino-lateral
      pulmonary-cava anasthomosis. After the anasthomoses were completed hearts were
      reperfused for 30 min; then hearts were excised and specimens were taken for
      biochemical and morphological studies. These were conducted on three groups of
      hearts: (A) hearts reimplanted and reperfused without treatment of the donor or
      of the recipient animal; (B) hearts subjected to the same procedure but in the
      presence of U-74389G treatment of donors and recipient rats; (C) control hearts
      rapidly excised from normal, non-operated animals. Electron microscopy studies
      showed, in hearts transplanted without treatment, the typical morphological
      aspects of lipoperoxidative injury: swollen mitochondria with disrupted cristae,
      damaged endothelial cells with the nucleous bulging into the lumen and a
      discontinued endothelial lining with diffuse oedema among the fibers. Lazaroid
      treatment attenuated most of these damages in hearts of group B. As for the
      biochemical findings, the hearts transplanted in the presence of U-74389G
      treatment had significantly higher ATP and creatine phosphate levels (P < 0.01)
      and lower malondialdehyde concentrations (P < 0.05) with respect to the hearts
      transplanted without treatment. Furthermore, serum creatine kinase activity was
      lower in treated than in untreated recipient animals (P < 0.05). Taken together,
      all these results indicate that U-74389G treatment is effective in protecting
      cardiac muscle from structural and functional ischaemia-reperfusion injuries, at
      least from those arising during a heart transplantation procedure.

PMID- 8981554
TI  - Efficacy and pharmacokinetics of gallopamil in patients with coronary artery
      disease.
AB  - We prospectively studied 10 patients with stable exertional ischaemia, selected
      from a larger group of patients referred for suspected coronary artery disease or
      to detect residual ischaemia after myocardial infarction, to evaluate
      pharmacokinetic changes during chronic treatment with gallopamil and its
      correlation with clinical efficacy in patients with coronary artery disease. Our
      study consisted of a 1-week run-in single-blind placebo treatment and a 4-week
      single-blind gallopamil treatment. At the end of the run-in period patients
      underwent two different exercise tests, the first 2 hours and the second 7 hours
      after placebo administration. During active treatment all patients underwent two
      different exercise tests, the first 2 hours and the second 7 hours after
      gallopamil (50 mg) administration on the 1st and 28th days of gallopamil therapy.
      On the same days in eight of the patients we evaluated gallopamil pharmacokinetic
      changes. Our data revealed a rapid increase of unchanged gallopamil and its
      metabolite (norgallopamil) in the plasma, and a peak concentration of these
      substances about 2 hour after oral administration on both the 1st and 28th day of
      observation. Moreover, our results demonstrated an increase between the first and
      28th day of treatment in peak concentration of unchanged gallopamil in the
      plasma, and of AUC 0-infinity and AUC o-c values during chronic treatment with
      gallopamil. Our clinical data showed an improvement in exercise results during
      gallopamil therapy related to increased concentration of the drug.

PMID- 8981555
TI  - Characterization of alpha-difluoromethylornithine resistant Leishmania donovani
      and its susceptibility to other inhibitors of the polyamine biosynthetic pathway.
AB  - The promastigote form of Leishmania donovani is sensitive to growth inhibition by
      DL-alpha-difluoromethylornithine, an irreversible inhibitor of ornithine
      decarboxylase, exhibiting an IC50 of 125 microM. Exposure of a wild type cell
      population to gradually increasing concentrations of DL-alpha
      difluoromethylornithine resulted in the selection of a strain of Leishmania,
      which was capable of proliferating in 5 mM DFMO with an IC50 value of 10 mM. This
      resistant strain showed increased ornithine decarboxylase activity and higher
      levels of putrescine. It was sensitive to growth inhibition by bis (benzyl)
      analogs of spermine and a potent S-adenosylmethionine decarboxylase inhibitor,
      CGP 40215A. These results indicate the potential value of other inhibitors of the
      polyamine biosynthetic pathway as therapeutic agents in conditions where ODC
      inhibitors are ineffective.

PMID- 8981556
TI  - Prediction of blood cyclosporine concentrations in haematological patients with
      multidrug resistance by one-, two- and three-compartment models using Bayesian
      and non-linear least squares methods.
AB  - The blood cyclosporine (CsA) concentration-time profile in each of 24 adult
      haematological patients with multidrug resistance taking the first course of CsA
      treatment was fitted by one-, two- and three-compartment models to obtain
      relevant pharmacokinetic parameters. The pharmacokinetic parameters obtained were
      implemented into the PKS program (Abbottbase Pharmacokinetic System) as the
      population pharmacokinetic parameters used to predict blood CsA concentrations in
      adult haematological patients with multidrug resistance. The predictions of blood
      CsA concentrations by one-, two- and three-compartment models using the Bayesian
      method (BM) and the non-linear least squares method (NLLSM) were evaluated
      employing 11 patients who took the second course of CsA treatment. While the
      Akaike's information criterion (AIC) favoured the two-compartment model to
      describe CsA concentration-time profiles in patients taking the first and second
      courses of CsA treatment, the predictive performance analyses showed that both
      two- and three-compartment models were better than the one-compartment model for
      prediction, but the three-compartment model was slightly superior to the two
      compartment model. The results also show that the predictions using BM were
      slightly better than those using NLLSM. Several factors affecting BM predictions
      and the possible difference among AIC, BM and predictive performance analyses
      were also addressed.

PMID- 8981557
TI  - Neuroprotective effects of felbamate on global ischaemia in Mongolian gerbils.
AB  - Felbamate is an antiepileptic drug whose action appears to occur mainly through
      an interaction with neurotransmission mediated by excitatory amino acids. We
      assessed its effectiveness in a model of transient global ischaemia in Mongolian
      gerbils. Dizocilpine (MK 801) was used for comparison. Treatment was given 10 min
      after transient forebrain ischaemia which was performed by occluding both common
      carotid arteries for 10 min. Felbamate (300 mg/kg i.p.) increased the number of
      surviving neurons in the CA1, CA2 and CA3 hippocampal cells. In particular, the
      CA1 area had a significantly higher number of surviving pyramidal neurons than
      that of vehicle-treated animals (67 +/- 11 vs 33 +/- 6 surviving neurons/mm; P <
      0.05). No significant difference in density of surviving neurons was observed
      between dizocilpine (3 mg/kg i.p.) and vehicle (54 +/- 10 vs 33 +/- 6 surviving
      neurons/mm). The EEG results indicated that the effect of felbamate, used alone,
      is the same in the ischaemic-vehicle group as non-ischaemic group. Our results
      show that felbamate exerts neuroprotective effects in a model of severe cerebral
      ischaemia.

PMID- 8981558
TI  - Indirect parasympathomimetic activity of metoclopramide: reversible inhibition of
      cholinesterases from human central nervous system and blood.
AB  - Inhibitory effects of the dopamine D2-receptor antagonistic benzamide compound
      metoclopramide (MCP) on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes of
      both erythrocytes and human caudate nucleus and on human serum cholinesterase
      (ChE; EC 3.1.1.8) were studied in vitro using a spectrophotometric assay with
      acetylthiocholine (ASCh) as substrate. MCP concentrations in the assays varied
      from 0.30 microM to 0.15 mM. All isoenzymes studied were inhibited by
      metoclopramide in a concentration-dependent manner. MCP inhibition of AChE and
      ChE isoenzymes was not time-dependent and of the reversible type. Double
      reciprocal plots of the reaction velocity against varying ASCh concentrations
      revealed that, for AChE isoenzymes of erythrocytes and of the caudate nucleus,
      MCP reduced both maximal reaction velocity (Vmax) and substrate affinity
      (apparent Michaelis constant, KM, increased). Thus, MCP inhibition of both AChE
      isoenzymes was of mixed competitive/non-competitive type. MCP constants for
      reversible competitive (Ki) and non-competitive (Ki) inhibition could be
      determined for erythrocyte AChE (Ki = 10 microM; Ki = 70 microM) and caudate
      nucleus AChE (Ki = 9.3 microM; Ki = 82 microM). In contrast to MCP inhibition of
      AChE isoenzymes, the type of reversible MCP inhibition of human serum ChE
      depended on substrate concentration. If substrate concentration exceeded 0.2 mM,
      MCP inhibition was of mixed competitive/non-competitive type (Ki = 0.19 microM;
      Ki = 1.4 microM). MCP inhibition was of uncompetitive type, if substrate
      concentration was below 0.2 mM (Ki(u) = 1.0 microM). The mixed-type MCP
      inhibition of cholinesterase isoenzymes, because of its non-competitive
      component, can only partially be overcome by increased concentrations of the
      cholinergic transmitter acetylcholine (ACh). Since, with intravenous infusions,
      peak MCP plasma concentrations in humans reach 4 microM, MCP inhibition of ACh
      hydrolysis in vivo may contribute both to prokinetic and anti-emetic actions of
      the substance and to its extrapyramidal side effects.

PMID- 8981559
TI  - Behavioural effects of pinoline in the rat forced swimming, open field and
      elevated plus-maze tests.
AB  - Pinoline (6-methoxy-1,2,3,4-tetrahydro-beta-carboline) is a naturally occurring
      compound in the mammalian body which inhibits serotonin (5-hydroxytryptamine)
      uptake and monoamine oxidase-A activity. The present study was designed to assess
      potential antidepressant- or anxiolytic-like behavioural effects of pinoline in
      rat forced swimming, open field and elevated plus-maze tests. In the forced
      swimming test pinoline dose-dependently reduced the immobility time, starting
      from a dose of 8 mg kg-1. In the open field test pinoline reduced the total open
      field activity. This effect was significant at 20 mg kg-1, whereas the dose of 15
      mg kg-1 only significantly reduced the number of rearings. In the plus-maze test
      pinoline decreased the total number of arm entries, the number of line crossings
      and time spent in the open part of the apparatus, but increased the number of
      approaches to the open part of the maze. The effects of pinoline were dose
      dependent in all three behavioural tests used. Since antidepressant drugs reduce
      the immobility time in the forced swimming test but typically inhibit activity in
      open field and elevated plus-maze tests, the behavioural effects of pinoline
      resemble those of drugs with an antidepressant profile.

PMID- 8981560
TI  - Pharmacological studies of cardamom oil in animals.
AB  - Cardamom seeds are widely used for flavouring purposes in food and as
      carminative. Little information has been reported on their pharmacological and
      toxicological properties or, for their volatile oil which constitutes about 5% of
      the seed's total weight. A comparative study of the anti-inflammatory activity of
      the oil extracted from commercial Elettaria cardamomum seeds, in doses of 175 and
      280 microliters/kg and indomethacin in a dose of 30 mg/kg against acute
      carrageenan-induced planter oedema in male albino rats was performed, which
      proved to be marked. Moreover, investigation of the analgesic activity using p
      benzoquinone as a chemical stimulus proved that a dose of 233 microliters/kg of
      the oil produced 50% protection against the writhing (stretching syndrome)
      induced by intraperitoneal administration of a 0.02% solution of p-benzoquinone
      in mice. In addition the antispasmodic activity was determined on a rabbit
      intestine preparation using acetylcholine as agonist, the results proving that
      cardamom oil exerts its antispasmodic action through muscarinic receptor
      blockage.

PMID- 8981561
TI  - Repaglinide preserves nutrient-stimulated biosynthetic activity in rat pancreatic
      islets.
AB  - The meglitinide analogue repaglinide is a novel non-sulphonylurea insulinotropic
      agent which, like hypoglycaemic sulphonylureas, causes the closing of ATP
      sensitive K+ channels in islet cells. We have now explored the effect of
      repaglinide upon proinsulin biosynthesis in rat pancreatic islets. Groups of
      eight islets each were incubated for 90 min in the presence of L-[4
      (3)H]phenylalanine (4 microM) and glucose (2.8 or 16.7 mM), in the absence or
      presence of repaglinide (10 microM). A rise in glucose concentration caused a
      four-fold increase of the incorporation of L-[4-(3)H]phenylalanine into TCA
      precipitable material. Repaglinide failed to adversely affect protein
      biosynthesis, whether at low or high glucose concentrations. Further
      characterization of the biosynthetic response was achieved by separation of the
      tritiated peptides by gel filtration. In the absence of repaglinide, the
      (pro)insulin/total ratio of tritiated peptides averaged 33.3 +/- 10.2 and 58.7 +/
      1.7% (n = 6 in both cases) at 2.8 and 16.7 mM D-glucose, respectively.
      Repaglinide again failed to significantly affect such ratios. In conclusion,
      repaglinide may offer the advantage over hypoglycaemic sulphonylureas of
      preserving nutrient-stimulated biosynthetic activity in pancreatic islet cells.

PMID- 8981562
TI  - Climatotherapy of psoriasis and hypertension in elderly patients at the Dead-Sea.
AB  - The responses of various age-groups of psoriatic patients to a four-week period
      of climatotherapy at the Dead-Sea was compared in three separate studies. In the
      first study, plaque clearance following climatotherapy was evaluated in a group
      of 688 psoriatics, as a function of age, sex and duration of the disease. Neither
      the age of the patient when treated, nor the duration of the disease, appeared to
      influence the degree of plaque clearance. However, when the age at onset of the
      disease was evaluated as the comparative parameter-a decrease in the rate of
      response with increasing patients' age was recorded. In the second study, the
      type and incidence of side effects after climatotherapy was studied in 502
      patients aged over 65, and in more than 4,500 younger psoriatics. There was no
      difference in the type and frequency of side effects between the two age-groups.
      The most frequent side effects were: slight sun burn (8.2%), sun allergy (5.0%),
      common cold (3.4%), leg oedema (2.0%), diarrhea (1.4%) and herpes simplex (0.8%).
      In all cases the side-effects disappeared within a few days. In the third study,
      the reduction in the diastolic and systolic blood pressures in a group of 1,142
      hypertensive psoriatics was evaluated as a function of time. It was demonstrated
      that while there was no significant age-dependent difference in lowering their
      diastolic blood pressure throughout the study, differences in lowering systolic
      measurements between the younger (< 40 y) and older (> 65 y) hypertensive
      patients were highly significant. On the basis of these studies we conclude that
      psoriatics aged 65 and over benefit from climatotherapy at the Dead-Sea no less
      than younger patients, and that, irrespective of age, high blood pressure is not
      a contraindication for this treatment in psoriatic patients at the Dead-Sea.

PMID- 8981563
TI  - Pharmacology of reticulospinal vasomotor neurons in cardiovascular regulation.

PMID- 8981564
TI  - Paracrine control of adrenal cortical function by medullary chromaffin cells.

PMID- 8981565
TI  - Muscarinic receptor subtypes and smooth muscle function.

PMID- 8981566
TI  - International Union of Pharmacology. XII. Classification of opioid receptors.

PMID- 8981567
TI  - Neutrophils and myocardial reperfusion injury.
AB  - Ischaemia induces an acute inflammatory response in myocardial tissue with an
      early phase of neutrophil accumulation, which is accelerated by reperfusion. In
      experimental models, interventions that deplete neutrophils or inhibit their
      function cause a significant reduction in myocardial infarct size. These cells,
      therefore, may exacerbate tissue injury through the release of free radicals and
      proteolytic enzymes. Neutrophil recruitment depends on the presence of
      inflammatory mediators. Leukotriene B4, interleukin 8 and the complement fragment
      C5a have been implicated in this process. Studies using antibodies to the
      selectin, integrin and immunoglobulin superfamily adhesion molecules indicate
      that they also have a crucial role in myocardial neutrophil recruitment.

PMID- 8981568
TI  - Botulinum toxin as a therapeutic agent.
AB  - Botulinum toxin is a presynaptic neuromuscular blocking agent that, when injected
      intramuscularly in minute quantities, can produce selective muscle weakness. This
      property is employed therapeutically to provide symptomatic relief in conditions
      related to excessive muscle activities in strabismus, blepharospasm, hemifacial
      spasm, cervical dystonia, spasmodic dysphonia (adductor type), and jaw closing
      dystonia. It is investigational for a long list of medical conditions. It is a
      marketed drug in a number of countries in the world, but its use has only been
      approved by different regulatory agencies for use in a limited number of
      conditions. The long-term effects, appropriate dose for children, and in
      pregnancy, and maximum dose without causing toxicity remain unclear.

PMID- 8981569
TI  - The neurotransmitter candidature of sulphur-containing excitatory amino acids in
      the mammalian central nervous system.
AB  - While L-glutamate (L-Glu) is considered to be the predominant excitatory amino
      acid transmitter in the mammalian CNS, other amino acids have come under scrutiny
      as possible rivals for such a role. These include four sulphur-containing
      analogues of L-Glu and L-aspartate known as the SAAs. The L-Glu analogues are L
      homocysteic acid and L-homocysteine sulphinic acid, while the L-aspartate
      analogues are L-cysteic acid and L-cysteine sulphinic acid. They are mixed
      agonists of excitatory amino acid receptors on a variety of neurones and are
      reported to be present in and released from mammalian CNS tissue. This review
      serves to summarize the current state of research into the possibility that one
      or more of these compounds is indeed a transmitter within the mammalian CNS.

PMID- 8981570
TI  - Molecular and clinical aspects of apoptosis.
AB  - Unwanted cells are removed by physiological cell death processes that are highly
      conserved throughout the animal kingdom. Physiological cell death plays an
      important role in development, tissue homeostasis and defence against viral
      infection and mutation. This review describes the molecular components that
      implement this process, the relevance of these to a variety of human diseases,
      and discusses the potential for novel therapies based on our understanding of
      them.

PMID- 8981571
TI  - Pharmacology of nicotine and its therapeutic use in smoking cessation and
      neurodegenerative disorders.
AB  - During the last decade, nicotine has been used increasingly as an aid to smoking
      cessation and has been found to be a safe and efficacious treatment for the
      symptoms of nicotine withdrawal. This period has also seen significant advances
      in our understanding of the mechanisms underlying the psychopharmacological
      responses to nicotine, including, particularly, those that have been implicated
      in nicotine addiction. This paper reviews this decade of progress in the specific
      context of the therapeutic application of nicotine to the treatment of smoking
      cessation. Other putative future applications, particularly in the treatment of
      neurodegenerative disorders, are also reviewed.

PMID- 8981572
TI  - Platelet activation during myocardial ischaemia: a contributory arrhythmogenic
      mechanism.
AB  - Experimental and clinical observations of the involvement of platelets in the
      pathophysiology of myocardial ischaemia indicate the importance of interactions
      between these formed elements and the heart. The aim of this review is to outline
      evidence linking platelet activation, myocardial ischaemia and infarction, and to
      present evidence for a link between platelet activation, arrhythmogenesis and
      sudden death. A brief review of platelet physiology and pharmacology is provided,
      with a review of the cardiac electrophysiological effects of ischaemia and the
      electrophysiological effects of platelet-derived substances. The concept that
      platelet activation during myocardial ischaemia is a contributory arrhythmogenic
      mechanism is discussed.

PMID- 8981573
TI  - The endothelin system and its potential as a therapeutic target in cardiovascular
      disease.
AB  - Endothelin (ET)-1, an endothelium-derived peptide, is the most potent
      vasoconstrictor agent described to date. ET-1 also has positive inotropic and
      chronotropic effects in the heart and is a co-mitogen in both cardiac and
      vascular myocytes. The major elements of the system involved in formation of ET-1
      and its isopeptides, as well as the receptors mediating their effects, have been
      cloned and characterised. Antagonists of the ET receptors are now available, and
      selective inhibitors of the ET-converting enzymes are being developed. Early
      studies using receptor antagonists support the involvement of ET-1 in the
      pathophysiology of several cardiovascular diseases. The relative merits of ET
      converting enzyme inhibitors and receptor antagonists for the treatment of
      cardiovascular disease are discussed.

PMID- 8981574
TI  - Apoptosis and gastrointestinal pharmacology.
AB  - Apoptosis is a fundamental biological process that regulates cell number and
      removes cells that are neoplastic or infected by viruses. This review summarises
      present knowledge of the mechanisms and genetic regulation of apoptosis in the
      gastrointestinal tract and highlights areas of pharmacological relevance. In the
      intestine, apoptosis occurs in the crypt and possibly at the villus tip. Abnormal
      apoptosis plays a role in a number of gastrointestinal disease including
      colorectal cancer. The effects of cytotoxic drugs, chemical carcinogens,
      nonsteroidal anti-inflammatory drugs, short-chain fatty acids, bile salts and
      anthraquinolones on apoptosis in the gastrointestinal tract are reviewed.

PMID- 8981575
TI  - Methodological considerations in neurobehavioral teratology.
AB  - Neurobehavioral teratology is a rapidly expanding field benefitting from recent
      advances in neurobiology and behavior and from the increasing availability of
      compounds with specific pharmacological actions. There is evidence that data
      derived from animal studies are clinically pertinent and hence animal studies are
      useful in extending clinical findings, in anticipating consequences of early drug
      exposure and, by determining the underlying neural mechanisms, in developing
      therapeutic approaches. However, the usefulness of animal studies crucially
      depends on the reliability and sensitivity of the methods used. We highlight the
      importance of appropriate selection of the route, dose, frequency, duration and
      timing of drug administration. We also emphasize the importance of not
      confounding treatment with litter effects and suggest that either the litter be
      used as the unit of analysis, or that each litter contribute only one pup to each
      test condition. We discuss the question of the time of testing and of testing,
      not only under baseline conditions, but also in conditions in which the offspring
      are exposed to stressful, pharmacological or cognitive challenges. We hope that
      future studies will benefit from these considerations and avoid the
      methodological weaknesses that beset some of the early studies in this field.

PMID- 8981576
TI  - On mouse pups and their lactating dams: behavioral consequences of early exposure
      to oxazepam and interacting factors.
AB  - Behavioral analysis in animal models appears to be a valuable and sensitive tool
      for detecting subtle alterations in CNS function, which can be produced by early
      exposure to small perturbations of sensory experience, hormonal milieu, or
      exposure to psychotropic agents devoid of major teratogenic potential. Concerning
      anxiolytics, the more recent work in mice, which is here summarized, was carried
      out by putting the emphasis on changes in naturally occurring species-typical
      social responses as a function of early exposure to benzodiazepines. For adult
      females, on the behavior expressed during the early postpartum period, whereas
      for infant subjects, on the ontogenetic stage of the establishment of social
      bonding. Critical issues such as the choice of fostering procedure and rearing
      conditions are also addressed. Evidences of relationships between changes in
      social milieu taking place during early rearing-i.e., when dramatic transitions
      in the neurochemical target system occur- and the adult behavioral response to
      challenges with BDZ agents are presented. These data strengthen the notion that
      the modes of reaction of adult animals to the joint influence of physiological
      and environmental (stimulus) variables are under the influence of events in early
      ontogenesis. Therefore, a better understanding of the mechanisms-as unveiled by
      an appropriate use of drug tools-that mediate such a plasticity might have
      considerable psychobiological and clinical-therapeutical relevance.

PMID- 8981577
TI  - Evaluation of perinatal flumazenil effects on the behavior of female RLA/Verh
      rats in anxiety tests and shuttle box avoidance.
AB  - The present study investigated the effects of perinatal flumazenil (Ro 15-1788, a
      benzodiazepine receptor antagonist), given from gestational day 15 to the 14th
      day after giving birth, at two doses (3.5 and 6.3 mg/kg/ day) on the behavior of
      female RLA/Verh rats. This rat line has been selectively bred for non-acquisition
      of two-way active avoidance. Offspring of treated/non-treated dams were tested
      when adults for two-way active (shuttle box) avoidance acquisition. For
      comparison reasons additional offspring coming from the same treatments were used
      in an hyponeophagia test and in both an open field and a plus maze tests. The
      results show that perinatal flumazenil, specially the lower dose (and also the
      highest dose, although only in the final phases of the shuttle box training) was
      able to improve two-way active avoidance acquisition, as it has been previously
      found with males, whereas it failed to show any effect in the hyponeophagia task,
      the open field and the plus-maze tests. As two-way active avoidance acquisition
      can be enhanced both by reducing emotionality/anxiety or by improving memory, it
      is suggested that flumazenil treatment could have affected either one or both
      processes.

PMID- 8981578
TI  - Developmental and behavioral effects of prenatal primidone exposure in the rat.
AB  - Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on
      gestation days 8-17 in doses of 0.40, and 80 mg/kg. Although these doses of PRM
      did not produce significant differences in litter size, birth weight, mortality,
      date of attainment of developmental landmarks or measures of preweaning reflex
      and motor development, there were a number of significant differences that
      developed as the animals approached and entered adulthood. When tested as adults,
      the 80 mg/kg male rats showed a deficit in the performance of an eight-arm radial
      maze task. These same animals showed a significant reduction in open field
      activity when tested as adults. In addition, both male and female PRM-treated
      animals showed reduced body weights at different periods corresponding to onset
      of sexual maturation during development. These findings are consistent with the
      larger body of literature reporting on the neurobehavioral teratology of
      phenobarbital, including its ability to produce lesions in the hippocampus and
      endocrine dysfunction resulting in reproductive deficits. These results suggest
      that PRM produces its adverse effects as a result of its metabolism to
      phenobarbital, which in turn affects the limbic system.

PMID- 8981579
TI  - What research with animals is telling us about alcohol-related neurodevelopmental
      disorder.
AB  - The substantial advances in understanding fetal alcohol syndrome over the past 20
      years were made in large part because of research with animals. This review
      illustrates recent progress in animal research by focusing primarily on the
      central nervous system effects of prenatal alcohol exposure. Current findings
      suggest further progress in understanding consequences, risk factors, mechanisms,
      prevention and treatment will depend on continued research with animals.

PMID- 8981580
TI  - Teratogenic actions of ethanol in the mouse: a minireview.
AB  - The deleterious effects of prenatal ethanol exposure have been extensively
      documented in clinical and experimental studies. This paper provides an overview
      of work conducted with mice to examine the myriad of adverse consequences that
      result from embryonic/fetal exposure to ethanol. All of the hallmark features of
      the clinical fetal alcohol syndrome have been demonstrated in mice, including
      prenatal and postnatal growth retardation, structural malformations and
      behavioral abnormalities associated with central nervous system dysfunction. As
      expected, the severity and profile of effects is related to both dosage level and
      timing of exposure. In addition, these effects have been demonstrated following
      acute and chronic exposure, with a variety of routes of administration employed.
      Furthermore, a number of strains have been used in these studies and the variant
      response (susceptibility) to the teratogenic actions of ethanol exhibited among
      different mouse strains support the notion that genetic factors govern, at least
      in part, vulnerability to these effects of ethanol. More recent studies using
      mouse models have focused on examining potential mechanisms underlying the full
      spectrum of ethanol's teratogenic actions.

PMID- 8981581
TI  - Effects of prenatal alcohol exposure on activity and learning in Sprague-Dawley
      rats.
AB  - Nulliparous pregnant Sprague-Dawley rats were exposed to ethanol via a liquid
      diet technique (FAE, fetal alcohol exposure) or administered a fixed amount of
      control diet from gestational day 11 to day 21. The offspring, at 2-3 months of
      age, were studied in tests of mechanically monitored motor activity and learning
      acquisition in an automatized testing cage requiring an instrumental
      discriminative response, where the ability to learn and relearn correlations of a
      light signal to water presentation was monitored. A significantly reduced
      activity (i.e. ramp mounting behaviour) in a novel situation was obtained in the
      FAE group compared to controls. The initial disruption of ramp mounting behaviour
      could reflect alterations in either habituation to a novel test situation,
      altered neophobia, or some retardation in associating these responses with the
      outcome of water-availability. Adult FAE rats (six months of age) showed a
      tendency towards a lowered acquisition performance (p = 0.06) when tested in a
      circular Morris-type swim maze, but no detectable differences were shown in a
      motor activity test chamber situation.

PMID- 8981582
TI  - Prenatal binge-like alcohol exposure alters neurochemical profiles in fetal rat
      brain.
AB  - The majority of studies examining the effects of prenatal exposure to alcohol on
      neurotransmitter levels have furnished results that are divergent (increase,
      decrease or no change). The present study assessed six neurochemical compounds
      [norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC),
      serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), gamma-aminobutyric acid
      (GABA)] from the same brain tissue. Pregnant Sprague-Dawley rats were given 5.1
      g/kg alcohol (by gavage) either daily from embryonic day 1 (E1) through E20 or
      E20 only. In addition, pairfed/intubated (PF/INT) and ad lib chow (Chow) groups
      were included as controls. The dams were sacrificed and the fetuses were removed
      on E20. Binge-like alcohol exposure throughout gestation (E1-E20) produced
      significantly higher brain to body weight ratios compared with all other groups.
      Alcohol exposure did not produce changes in NE levels, although the E1-E20
      exposure to alcohol reduced the contents of DA and 5-HT compared with the PF/INT
      and Chow controls. In addition, the E20 alcohol treatment reduced both DA and 5
      HT levels compared with the E1-E20 alcohol treatment. DOPAC and 5-HIAA contents
      were affected by the prenatal treatments insofar as the 5-HIAA levels were
      decreased in E/1-20 and E20 animals relative to both controls, while the DOPAC
      levels were decreased in E/1-20, E20 and PF/INT groups compared to the Chow
      group; however, both metabolites were unaffected by the difference in alcohol
      treatment duration. Moreover, GABA levels were increased in fetuses exposed to
      alcohol from E1-E20 compared with all other groups. Collectively, these findings
      suggest that binge-like alcohol exposure prior to and during neurotransmitter
      development affects the baseline content of several neurotransmitters.

PMID- 8981583
TI  - Temporal determinants of neonatal alcohol-induced cerebellar damage and motor
      performance deficits.
AB  - The timing and duration of alcohol exposure was manipulated in neonatal rats by
      using a "binge" model of alcohol exposure during the "third trimester
      equivalent." Groups of Sprague-Dawley rats were exposed to binges via artificial
      rearing on postnatal days (PD) 4-9, on PD 4-6 or on PD 7-9, which produced peak
      blood alcohol concentrations representative of human alcohol abusers
      (approximately 250 mg/dl). Motor performance was assessed using parallel bar
      traversal on PD 42-44, and total Purkinje cell numbers were determined by using
      the 3-dimensional stereological optical fractionator method. PD 4-9 binge
      exposure induced the most severe Purkinje cell loss (to 68% of controls) and PD 4
      6 binge exposure also produced significant loss (to 86% of controls), whereas PD
      7-9 binge exposure had no significant effect (98% of controls). Unexpectedly, all
      three alcohol treatments resulted in significant impairments on the parallel bar
      task. The time of exposure during the early neonatal period in rats strongly
      influences the degree of Purkinje cell loss, but Purkinje cell loss is not
      necessary for the alcohol-induced motor performance deficits. Both
      neuromorphological and neurobehavioral assessments are needed for a full
      description of alcohol-related neurodevelopmental disorders.

PMID- 8981584
TI  - Prenatal alcohol exposure influences the effects of neuroactive steroids on
      separation-induced ultrasonic vocalizations in rat pups.
AB  - Fetal alcohol exposure has been reported to be associated with hyper
      responsiveness to stress. Using a maternal separation paradigm, this study
      examined whether prenatal alcohol exposure affected sensitivity to neurosteroid
      modulation of stress. We have shown that the neuroactive steroid allopregnanolone
      reduces ultrasonic vocalizations (USVs) after brief maternal separation in week
      old rat pups. Prenatal alcohol exposure, however, resulted in reduced sensitivity
      to this neurosteroid. In this study's first experiment, the behavioral effects of
      pregnenolone sulfate, a neurosteroid with reportedly opposite modulatory effects
      on the GABAA receptor, were characterized. Pregnenolone sulfate had a triphasic
      effect on the production of ultrasonic vocalizations and on open field activity.
      Blockade of conversion of pregnenolone sulfate to allopregnanolone via the 5
      alpha-reductase inhibitor 4-MA also blocked the drug-related reduction in USVs,
      but not the higher-dose augmentation. The enzyme inhibitor alone had no
      significant effects on USV production, nor did progesterone. These results
      suggest that the neuroactive steroid pregnenolone sulfate may play an independent
      role in the stress response after maternal separation as well as being a
      precursor for the anxiolytic neurosteroid allopregnanolone. In the second
      experiment, prenatal alcohol exposure was found to eliminate both the low dose
      USV-reducing effect and the higher dose USV-increasing effect. These results
      support previous results demonstrating that prenatal alcohol exposure may cause
      an altered sensitivity to the neuromodulatory effects of neurosteroids.

PMID- 8981585
TI  - Androstenedione synergizes with stress or prenatal drug exposure to retard fetal
      growth: role of IGF.
AB  - Pregnant Sprague-Dawley dams were implanted with a Silastic capsule (3 or 10 mm)
      containing androstenedione (AN) or cholesterol prior to being administered one of
      several treatments that create an endocrine profile of stress: maternal exposure
      to alcohol, pair feeding (PF), cocaine (COC), or restraint stress (RS). Controls
      (chow fed, CF) were left undisturbed during pregnancy. Treatments were
      administered from day 14 to day 22 of gestation. Fetuses were delivered by
      cesarean section on day 22. Results revealed that administration of AN to
      pregnant dams at a dose that does not influence fetal growth by itself can retard
      fetal growth in the presence of alcohol, PF, COC or RS. Data indicate that these
      effects are not directly attributable to changes in adrenocorticotropin (ACTH) or
      corticosterone levels. Preliminary results suggest a role for insulinlike growth
      factor (IGF) binding proteins (IGFBPs). Overall, these data demonstrate that AN
      can synergize with drugs and/or stress to enhance intrauterine growth retardation
      (IUGR). One underlying cause of this synergism between stress-related
      environmental events and androgenic actions on fetal growth may be increased
      expression of IGFBPs, which can sequester IGFs, thereby inhibiting their trophic
      actions on fetal and/or placental tissue.

PMID- 8981586
TI  - Gestational cocaine and ethanol exposure alter spontaneous and cocaine-induced
      behavior in weanling rats.
AB  - The developmental and behavioral effects of prenatal exposure to cocaine and/or
      ethanol were examined in rats. Pregnant rats received ethanol (E; 2 g/kg, b.i.d.)
      orally, cocaine (C; 6 mg/kg/day, IV), or both (C/E) on gestational days 8-20.
      Controls consisted of pair-fed (PF) and untreated (UNT) groups. Offspring were
      weighed and examined for developmental markers beginning postnatal day one (PD1).
      On PD21 pups were individually observed in an open-field following either an
      injection of cocaine (10 mg/kg, IP), an injection of saline, or no treatment.
      Drug-treated and PF dams ate less food and gained less weight than the UNT dams.
      C and E litters had slightly increased mortality rates. Pups from both the C and
      E groups appeared less sensitive to the locomotor stimulant effect of cocaine.
      Pups from the E group engaged in significantly less spontaneous stereotypic
      locomotion than UNT and PF pups, while male pups from the C group exhibited a
      decrease in spontaneous exploratory behavior. Thus, prenatal exposure to C or E
      altered spontaneous and/or cocaine-induced behavior in weanling-aged rats, while
      the C/E combination did not augment either effect.

PMID- 8981587
TI  - A murine model of prenatal cocaine exposure: effects on the mother and the fetus.
AB  - To develop and characterize a murine model for investigating the long-term
      effects of prenatal cocaine exposure, the present study established the route of
      drug administration and the doses to be used for pregnant C57BL/6 mice.
      Comparison of the effects of a high dose of cocaine (60 mg/kg) when gavaged or
      injected subcutaneously (SC) established patterns of pathology characteristic of
      administration route but no dominating logic for selecting one over the other
      route for prenatal studies; however, because of the fourfold greater brain
      levels, with no evidence of greater pathology, the SC route was selected. When
      injected daily during gestation days 12-18, the period of prenatal development of
      dopamine systems, cocaine at doses producing plasma concentrations consistent
      with its stimulatory effects reduced food ingestion and weight gains during
      pregnancy and fetal body and brain weights at term. The extent of these
      reductions was comparable to reports on babies exposed to cocaine prenatally.
      Furthermore, the present study suggests that maternal undernutrition is not a
      likely mediator of these perinatal effects and that differences in the amount of
      cocaine exposure may cause the contrasting effects of maternal cocaine noted in
      the human literature.

PMID- 8981588
TI  - Ethanol self-administration and motor deficits in adults C57BL/6J mice exposed
      prenatally to cocaine.
AB  - Daily injections of 10 mg/kg cocaine on gestation days 12-18 did not alter
      maternal weight gain or offspring birth weight, viability, growth, or adult
      weight compared to saline controls. Adult male and female offspring were food
      deprived and trained to lever press for ethanol. Responding on an FR2 schedule
      and ethanol intake (g/kg) were recorded as measures of the reinforcing effects of
      ethanol. Lever press duration was used to assess motor performance. Results
      demonstrate that C57 mice will work for and consume large quantities of ethanol
      and that prenatal cocaine exposure increased the amounts ingested by both male
      and female mice. Prenatal-cocaine-exposed males also exhibited motor deficits as
      indicated by longer response duration times compared to controls. The consumption
      of large amounts of ethanol exacerbated the motor impairment in prenatal-cocaine
      males and revealed such deficits in cocaine females. The present results
      demonstrate that maternal cocaine exposure, at doses having no observable effect
      upon pregnancy, birth, or offspring growth, can increase the consumption of
      ethanol and enhance its motor impairing effects on fully mature offspring.

PMID- 8981589
TI  - Monoamine transporters and the neurobehavioral teratology of cocaine.
AB  - Prenatal cocaine exposure has been associated with various postnatal behavioral
      abnormalities in human infants, and also with changes in locomotor activity,
      learning deficits, and altered responses to drug challenge in nonhuman offspring.
      Several studies have further demonstrated that cocaine exerts an activating
      effect on fetal behavior. A variety of mechanisms have been proposed to account
      for the neurobehavioral teratogenic effects of developmental cocaine treatment,
      including inhibition of fetal brain neurotransmitter uptake and fetal hypoxemia
      secondary to constriction of the uteroplacental vascular bed. In support of the
      hypothesis that cocaine effects may be mediated partly by monoamine uptake
      inhibition, we and other investigators have recently demonstrated the presence of
      functional dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporters
      in the fetal rat brain. Transporter-related cocaine recognition sites are found
      in a number of fetal brain areas and could mediate the acute effects of cocaine
      on these areas as well as developmental changes that are manifested postnatally.
      For example, DA transporter blockade may underlie the above-mentioned
      activational effects of cocaine on fetal behavior. Time-dependent changes in DA
      or 5-HT transporter expression produced by prenatal cocaine exposure could
      likewise play an important role in some of the behavioral effects observed when
      offspring are tested postnatally.

PMID- 8981590
TI  - Differential effects of prenatal cocaine and retinoic acid on activity level
      throughout day and night.
AB  - Prenatal cocaine exposure is associated with disrupted state control and lowered
      activity levels. Prenatal retinoic acid excess also influences activity levels in
      laboratory rats. Activity level is usually monitored during a brief period in
      young offspring. The effects of these drugs on pup activity levels throughout the
      day is unknown. There is also little information on the long-lasting effects of
      these teratogens in adult animals. We compared the daily activity of rats which
      were prenatally exposed to cocaine or retinoic acid (RA). Appropriate control
      groups were also used. The offspring were evaluated for activity levels in a
      neophobic situation and for a 22-h period in same-sex groups of 3 littermates. As
      both pups and adults, the cocaine groups were hypoactive while the RA group was
      hyperactive when first placed into the testing cage (neophobic situation).
      Similarly, during the remainder of the 22-h testing period, the pup and adult
      cocaine animals exhibited reduced activity levels while the RA animals exhibited
      elevated activity levels. Thus, prenatal cocaine and retinoic acid exposures
      affected offspring activity levels differently, both drugs have long-lasting
      neurobehavioral effects that persist into adulthood, and effects are influenced
      by time-of-day. Strain-dependent differences and mechanisms of action are
      discussed.

PMID- 8981591
TI  - Prenatal administration of buprenorphine in the rat: effects on the rest-activity
      cycle at 22 and 30 days of age.
AB  - Three doses of buprenorphine (BUP) were administered by osmotic minipump from day
      8 of gestation through parturition. In addition to 0.3, 1.0, and 3.0 mg/kg/day of
      BUP, a vehicle control group received sterile water via minipump and a nontreated
      control group was left undisturbed during pregnancy. All treated and control
      litters were fostered at birth to untreated dams. BUP produced a dose response
      reduction in maternal water intake and reduced maternal weight gain among the two
      high dose groups; resorptions and birthweight were unaffected. BUP increased
      perinatal mortality in the two high dose groups compared with the vehicle
      controls and produced inconsistent effects on postnatal growth. To examine the
      effects of BUP on the rest-activity cycle of the offspring, groups of 3
      littermates from each of the treated and control groups were tested for an 8 h
      observation period on electronic activity monitors at 22 and 30 days of age.
      Unlike previous effects described for prenatally administered methadone, a
      disruption in the rest-activity cycle was not observed for any of the BUP treated
      groups.

PMID- 8981592
TI  - Prenatal exposure to morphine affects juvenile play behavior and adult social
      behavior in rats.
AB  - The effects of morphine exposure in utero on play behavior and social behavior
      were investigated in a longitudinal study. Wistar rat dams were SC injected daily
      with saline (control) or 10 mg/kg morphine from day 8 to day 21 of gestation.
      Play behavior of the offspring was measured at 3 and 4 weeks of age and social
      behavior at 3 months of age. Pinning, a measure for play behavior and social
      grooming of the morphine-treated offspring were significantly elevated compared
      to saline controls, especially on day 21. The onset-latency of pinning behavior
      was not changed. Furthermore, prenatal morphine treatment resulted in more social
      approach and less social avoidance behavior in adulthood, whereas changes in
      general locomotor activity were not observed. The results are discussed in
      relation to the effects of in utero exposure of morphine on the development of
      incentive aspects of play and social behavior.

PMID- 8981593
TI  - Labor analgesia and infant brain development.
AB  - A large percentage of newborns are exposed to pharmacological agents that affect
      the brain in connection with pain management during labor. The two most commonly
      used agents are meperidine, administered intravenously or intramuscularly, and
      bupivacaine, administered by the epidural route. Over the years, infant
      behavioral assessments have been used in the neonatal nursery to identify labor
      analgesia regimens with minimal impact on neonatal status. However, considerable
      controversy has centered on the general issue of possible harm to the neonate
      from use of analgesia and anesthesia in obstetrics. Due to limitations on
      experiments in the obstetric situation and a lack of suitable animal models, the
      broader issues concerning the effects of these agents on the developing brain and
      possible long-term consequences for infant adaptive functioning have received
      little attention. A series of studies has recently been completed using a rhesus
      monkey model for administration of labor analgesia under controlled experimental
      conditions and long-term behavioral evaluation of infants. Most of the
      assessments, including those of cognitive function, were not influenced by
      perinatal analgesia. However, these studies have confirmed the neonatal
      depressant effects of meperidine and have suggested that the course of behavioral
      maturation during certain periods of infancy is influenced by both meperidine and
      bupivacaine administration at birth. These effects could occur as a result of
      effects on vulnerable brain processes during a sensitive period, interference
      with programming of brain development by endogenous agents, or alteration in
      early experiences.

PMID- 8981594
TI  - Prenatal exposure to morphine alters analgesic responses and preference for sweet
      solutions in adult rats.
AB  - In the present study, we examined long-term effects of prenatal morphine on pain
      response and on preference for sweet solutions. Pregnant Fischer 344 rats were
      given increasing doses of morphine (0.75-12.0 mg/day) in slow-release emulsion,
      during gestational days 12-18. Control rats were injected with vehicle and were
      either pair-fed to morphine rats, or ad libitum fed. At birth, all litters were
      culled to 8-10 pups (half males and half females) and cross-fostered to naive,
      surrogate dams. Testing began when rats were 10-12 week old. Rats prenatally
      exposed to morphine exhibited higher analgesia in response to a morphine
      challenge, and a greater preference for saccharin solution as compared with both
      control groups. These findings indicate that prenatal morphine induces long
      lasting alterations of systems involved in reward processes and in opiate
      analgesia, perhaps by modulating endogenous opiate systems.

PMID- 8981595
TI  - Developmental consequences of intermittent and continuous prenatal exposure to
      1,1,1-trichloroethane in mice.
AB  - The effects of 1,1,1-trichloroethane (TCE) on physical and behavioral development
      were examined in CD-1 mice prenatally exposed under two regimens. In the first
      study, pregnant mice were exposed to either 2,000 ppm TCE or filtered air for 17
      hrs. during gestational days (GD) 12-17. A third group remained untreated. The
      results revealed no differences on pregnancy outcome. TCE-exposed pups gained
      less weight, exhibited delays in developmental landmarks and acquisition of the
      righting reflex, had poorer performance on tests of motor coordination and
      exhibited delays in negative geotaxis relative to sham or untreated pups. A
      second experiment was designed to more closely parallel the intermittent, acute,
      high-concentration pattern of solvent abuse. Pregnant mice were exposed for 60
      min. to 8,000 ppm TCE or sham placement in exposure chambers three times/day
      during GD's 12-17. The results were very similar to what were obtained in the
      more continuous exposure study. TCE-exposed pups gained less weight, had delays
      in developmental landmarks and acquisition of the righting reflex and exhibited
      weaker grip strength, poorer negative geotaxis and less rooting intensity in
      comparison to sham pups. These data provide evidence for the behavioral and
      developmental teratogenicity of prenatal TCE exposure late in gestation.

PMID- 8981596
TI  - Decreased hypothalamic serotonin levels in adult rats treated neonatally with
      clomipramine.
AB  - Early postnatal treatment with the antidepressant drug clomipramine has
      repeatedly been shown to lead to behavioural and physiological changes in adult
      rats. To provide some neurochemical correlates to these studies we have measured
      a number of monoaminergic parameters in the brains of adult (one year old) rats
      that were treated twice daily with 15 mg/kg clomipramine from postnatal day 2-14.
      The most consistent finding was that the hypothalamic levels of serotonin (5-HT)
      were decreased and those of the dopamine metabolite dihydroxyphenylacetic acid
      (DOPAC) were increased in rats irrespectively whether they went through a range
      of behavioural and physiological tests or not. The numbers of beta-adrenoceptors
      in the frontal cortex and of alpha 2-adrenoceptors in the amygdala/piriform
      cortex were not changed. The decrease in hypothalamic 5-HT concentrations appears
      to be up to now the most consistent neurochemical alteration in adult rats that
      were neonatally treated with antidepressant drugs. It is, however, not clear what
      the relation is with the functional changes in these rats, that are proposed by
      some authors as an animal model for depression.

PMID- 8981597
TI  - Neurotoxicology and amino acid intake during development: the case of threonine.
AB  - The development of the central nervous system is highly dependent on an adequate
      supply of nutrients. In particular, protein and amino acid availability is of
      major concern during gestation and in early postnatal life. Numerous data have
      been published on some amino acids directly involved in brain functions as
      neurotransmitters or indirectly as precursors of neurotransmitters, but scant
      information is available on the possible consequences of hyperthreoninemia, a
      phenomenon repeatedly noted in clinical reports. The results of neurochemical and
      behavioral studies in the developing rat suggest that despite numerous possible
      effects of threonine on brain constituents, moderate hyperthreoninemia does not
      impair markedly the development of the central nervous system.

PMID- 8981598
TI  - Neuroanatomical and functional alterations resulting from early postnatal
      cerebellar insults in rodents.
AB  - This review examines neuroanatomical and functional alterations in rodents
      resulting from postnatal insults during cerebellar development. Treatments such
      as irradiation and methylazoxymethanol (MAM) administration produced near birth
      (< postnatal day 8 for irradiation treatment and < postnatal day 4 for MAM
      administration) result in more severe cerebellar damage than do similar
      treatments administered several days after birth. Prominent among the more severe
      alterations are foliation abnormalities, misalignment of Purkinje cells and
      continued multiple innervation of climbing fibers; few or none of these occur as
      a result of later treatments (> postnatal day 8 for irradiation treatment and >
      postnatal day 4 for MAM treatment). The functional alterations also differ:
      insults produced near birth result in hypoactivity, ataxia, tremor and
      accompanying learning deficits, whereas those produced later result in
      hyperactivity and few learning deficits. This hyperactivity may have relevance to
      human disorders. Brief discussions of cerebellar and functional alterations
      (e.g., hyperactivity) resulting from neonatal infection with the Borna disease
      virus and induction of hypo- and hyperthyroidism during the preweaning period are
      also presented.

PMID- 8981599
TI  - Neural grafting as a tool for the study and reversal of neurobehavioral birth
      defects.
AB  - The transplantation of fetal neurons has gained notoriety in recent years for its
      perceived potential to reverse neurological deficits caused by loss of one or
      another neuronal population. The present paper describes a neural grafting
      approach employed by our laboratory to gain more insight into the drug-induced
      neurobehavioral teratogenicity. Mice were exposed prenatally to phenobarbital by
      feeding the barbiturate to the pregnant dam on gestation days 9-18. Heroin
      exposure was accomplished by injecting dams during the same gestational period.
      At maturity, the drug-exposed offspring displayed profound deficits in specific
      behavioral tasks, suggesting alterations in the septohippocampal cholinergic
      pathway. Biochemically, we observed increased presynaptic activity in the
      pathway, which was not accompanied by a corresponding reduction in postsynaptic
      activity. Rather, there was a general hyperactivation along the different
      postsynaptic phases. In contrast, we noted a desensitization of protein kinase C
      activity in response to the exposure of a cholinergic agonist to the drug-exposed
      offspring. Subsequent transplantation of embryonic cholinergic cells from normal
      mice to the impaired hippocampus reversed the behavioral deficits, whereas sham
      operated controls exhibited no improvement. Concomitantly, all the biochemical
      alterations studied, both presynaptic and postsynaptic, were either partially or
      completely reversed following grafting.

PMID- 8981600
TI  - Similarities in genetic mental retardation and neuroteratogenic syndromes.
AB  - Principles and mechanisms of neurobehavioral teratogenesis are used to show
      commonalities between manifestations of abnormal development consequent to
      genetic abnormality or teratogenic exposure. A comparison and contrast of both
      the neuropathological and neuropsychological characteristics of children with
      early embryonic exposure to isotretinoin (Accutane) or with selected mental
      retardation syndromes is presented. Putative mechanisms of retinoid teratogenesis
      through the disruption of normal retinoid-triggered embryogenesis and the
      alteration of homeobox gene expression are discussed. Interference with homeobox
      gene expression as an avenue to the perturbation of early developmental processes
      and the production of hindbrain and craniofacial abnormalities is then proposed
      as a common basis for the translation and expression of several genetic mental
      retardation syndromes. Finally, dose-response effects and other modulators of
      vulnerability to abnormal development are used to provide a conceptual framework
      for the understanding of variability in the expression of genetically caused
      abnormalities.

PMID- 8981601
TI  - Paternal exposures: impact on reproductive and developmental outcome. An
      overview.
AB  - Experimental and epidemiologic investigations document the adverse consequences
      of an array of paternal exposures on the development of subsequent offspring.
      Male-mediated abnormalities have been reported after exposure to therapeutic and
      recreational drugs, to chemicals in the workplace and environment and to ionizing
      radiation. The impact on progeny outcome includes: an increase in congenital
      malformations, spontaneous abortions, fetal resorptions; low birth weight;
      increase in childhood cancers; developmental, neurobehavioral, neuroendocrine,
      neurochemical abnormalities; effects in F2 generation progeny. Fertility is often
      unaffected. The comparative influence of genetic, epigenetic and nongenetic
      mechanisms in the etiology of paternally-mediated adverse outcomes is unknown.
      There is no a priori reason to assume that male-mediated effects are limited to
      the agents studied to date. The broad spectrum of alterations recorded after
      exposure to a variety of unrelated agents suggests the need for a more focused
      effort and multidisciplinary exploration of the potential impact of the male
      parent on reproductive outcome.

PMID- 8981602
TI  - Blockade of behavioral effects of bretazenil by flumazenil and ZK 93,426 in
      pigeons.
AB  - Benzodiazepine receptor partial agonists manifest full efficacy in preclinical
      tests of anxiolytic drug action but do not fully reproduce the discriminative
      stimulus effects of benzodiazepine receptor full agonists in pigeons. The partial
      agonist, bretazenil, binds to both diazepam-sensitive and diazepam-insensitive
      GABAA receptors. Previous studies have suggested a role for each of these
      receptor populations in some behavioral effects of bretazenil in pigeons. A
      possible role for these receptor subtypes in the behavioral effects of bretazenil
      was further investigated through drug interaction studies with the benzodiazepine
      receptor antagonists, flumazenil and ZK 93,426. Whereas flumazenil binds with
      high affinity to both receptor isoforms, ZK 93,426 binds preferentially to
      diazepam-sensitive binding sites. Bretazenil markedly increased punished
      responding of pigeons without significantly affecting nonpunished responding. In
      pigeons discriminating the full benzodiazepine receptor agonist, midazolam, from
      saline, bretazenil produced only 60-75% maximal effect. Flumazenil and ZK 93,426
      neither increased punished responding nor substituted for midazolam, but dose
      dependently blocked the effects of bretazenil on punished responding. Flumazenil
      also dose-dependently blocked the effects of bretazenil in midazolam
      discriminating pigeons, whereas ZK 93,426 only attenuated this effect. These
      results indicate that bretazenil's actions as a partial agonist at diazepam
      sensitive benzodiazepine receptors mediate increases in punished responding and
      substitution for the discriminative stimulus effects of midazolam in pigeons. The
      differences in the effects of flumazenil and ZK 93,426 on the discriminative
      stimulus effects of bretazenil suggest a potential contribution of diazepam
      insensitive sites to this behavioral effect.

PMID- 8981603
TI  - Effects of tetrabenazine on methamphetamine-induced hyperactivity in mice are
      dependent on order and time-course of administration.
AB  - The ambulation-increasing effect of methamphetamine (MAP: 2 mg/kg s.c.) in mice
      persisted for about 3 h. Tetrabenazine (TBZ: 4 mg/kg s.c.), a depleter of
      monoamines from the cytoplasmic pool did not increase ambulation on its own.
      Pretreatment with TBZ at 1.5 h before administration of MAP inhibited the
      stimulant effect of MAP. In contrast, combined administration of two drugs
      resulted in a transient but considerable enhancement of MAPs stimulant effect.
      Post-MAP treatment with TBZ at 0.5-2 h hardly modified MAPs behavioral effects.
      In contrast, 3-6 h post-MAP treatment with TBZ induced a transient increase in
      activity, although the stimulant effect of MAP had already disappeared. The
      maximum increase in ambulatory stimulation was produced by 4-h post-MAP treatment
      with TBZ. The inhibitory effect of TBZ pretreatment on MAP-induced hyperactivity,
      as well as the transient hyperactivity elicited by TBZ when administered along
      with MAP, or 4 h after MAP, was dose-dependent. Preliminary studies revealed that
      transient hyperactivity was never produced by combination of GBR-12909 (a
      selective dopamine reuptake inhibitor) with TBZ or MAP with oxypertine (a
      selective norepinephrine releaser/depleter), but produced by combination of
      nialamide (a monoamine oxidase inhibitor) with TBZ. Inhibition of MAPs effects by
      TBZ pretreatment suggests that enhancement of dopamine release from cytoplasmic
      pool, and inhibition of dopamine reuptake by MAP, are involved in MAPs acute
      behavioral effects. Further, the fact that neither TBZ administration following
      GBR-12909 pretreatment, nor oxypertine treatment following MAP pretreatment,
      elicited transient hyperactivity suggests that dopamine is involved in
      hyperactivity elicited by post-MAP treatment with TBZ. It is also suggested that
      inhibition of monoamine oxidase (MAO) by MAP and dopamine displacement by TBZ may
      be responsible for the transient stimulation produced by 3-6 h post-MAP treatment
      with TBZ. It is hypothesized that the MAO inhibitory action of MAP persists after
      cessation of its acute stimulant effect, possibly up to 6 h after administration.

PMID- 8981604
TI  - Insulin-dependent attenuation in alpha 2-adrenoreceptor-mediated nociception in
      experimental diabetes.
AB  - Diabetes mellitus is associated with abnormalities in central noradrenergic
      dynamics, a system that appears to be involved in the regulation of nociception
      in both humans and experimental animals. To this end, we investigated the
      responsiveness of nociceptive threshold to the actions of clonidine (an alpha 2
      adrenoreceptor agonist) and yohimbine (an alpha 2-adrenoreceptor antagonist)
      during diabetes. The induction of diabetes was achieved by the administration of
      streptozotocin (STZ) (55 mg/kg, intravenously). Nociceptive threshold, as
      indicated by the tail-flick latency of the tail immersion test, was progressively
      elevated as a function of the duration of diabetes. Systemic administration of
      clonidine and yohimbine respectively produced dose-dependent analgesic and
      hyperalgesic effects in control animals. Both of these phenomena were impaired in
      chronically diabetic animals. In contrast, insulin-treated diabetics displayed
      supersensitivity to clonidine's antinociceptive effect, especially at low doses.
      Acute hyperglycemia did not interfere with the alpha 2-agonist-mediated elevation
      in nociceptive threshold. Attenuation in clonidine antinociceptive effect was
      also observed following its intrathecal administration to diabetic animals.
      Overall, these data suggest that the impaired responsiveness of diabetic rats
      might be due to a central alpha 2-adrenoreceptor desensitization and/or
      biochemical defect in the postreceptor events.

PMID- 8981605
TI  - Effects of D-cycloserine and aniracetam on spatial learning in rats with
      entorhinal cortex lesions.
AB  - A great body of behavioural and neurophysiological evidence suggests that
      excitatory amino acids are involved in mechanisms of learning and memory.
      Moreover, degeneration of glutamatergic pathways may underlie the cognitive
      deficits seen in various disorders such as Alzheimer's dementia. As direct
      stimulation of glutamatergic receptors with agonists may increase the risk of
      toxicity and accelerate neuropathological changes, a more valid approach seems to
      be positive modulation of glutamatergic receptors that may reverse the symptoms
      with a lower risk of excitotoxic effects. Such a possibility offered by partial
      agonists of the strychnine-insensitive glycine site of the NMDA receptor (Gly-B
      site) or positive modulators of AMPA receptors, such as aniracetam. In the
      present study, the effects of d-cycloserine and aniracetam were tested in two
      animal models of cognitive deficits (entorhinal cortex lesion-induced deficits
      evaluated in the radial maze and scopolamine-induced amnesia evaluated in passive
      avoidance test). D-cycloserine (6 mg/kg, for 10 days) had no effect on spatial
      working memory deficit induced by entorhinal cortex lesions. It did, however,
      reverse scopolamine-induced deficits in the passive avoidance test when given
      acutely at the same dose. In contrast, aniracetam (50 mg/kg, for 10 days)
      produced beneficial effects in the radial maze test in rats with entorhinal
      cortex lesions, but given at the same dose acutely did not influence scopolamine
      induced amnesia. The positive effect of d-cycloserine against scopolamine-induced
      amnesia may be probably related to the cholinergic-glutamatergic interaction in
      the hippocampus. The negative data obtained with d-cycloserine in the model of
      entorhinal cortex lesions-induced cognitive deficits could be taken as a hint
      that it is probably not suitable for the symptomatological therapy of Alzheimer's
      disease. The mechanism of positive action of aniracetam cannot be explained on
      the basis of AMPA receptor modulation, as the dose used (50 mg/kg) is well below
      that required for the effect at AMPA receptors. Other actions such as peripheral
      effects or modulation of metabotropic receptors seem more likely.

PMID- 8981607
TI  - The 5-HT2 receptor agonist MK-212 reduces food intake and increases resting but
      prevents the behavioural satiety sequence.
AB  - The 5-HT2c receptor is implicated in the relationship between serotonin and
      satiety. However, anorexia induced by the 5-HT2 receptor agonist 1-(2,5-dimethoxy
      4-iodophenyl)-2-aminopropane (DOI) has been shown to delay, not advance
      behaviours associated with the onset of satiety, fragmenting eating behaviour, 6
      chloro-2-(1-piperazinyl)pryazine (MK-212) is also a selective agonist at the 5
      HT2 receptor sites. MK-212 has greater affinity for 5-HT2c receptor sites than
      DOI. The effects of an ED50 dose of MK-212 (5.0 mg/kg i.p.) on the eating and
      other behaviours of the fasted rat were continuously monitored following the
      presentation of food. Continuous monitoring provides the most powerful and valid
      form of behavioural analysis. Temporal profiles of behaviour duration (dur) and
      frequency (frq) were generated. Food intake was reduced 54% by MK-212 (p < .001).
      The frequency of grooming was reduced (p < .01). Locomotion (dur p < .001, frq p
      < .001), rearing (dur p < .0005, frq p < .005) and sniffing (dur p < .05, frq p <
      .0001) were all reduced. The duration of resting increased (p < 0.01). This is
      consistent with enhanced satiety. However, the Behavioural Satiety Sequence was
      not present after the administration of MK-212 (5.0 mg/kg). The temporal
      structure of behaviour produced by MK-212 was quite different from that produced
      by pre-feeding. Initially resting dominated the behavioural profile. Eating
      increased over time from a suppressed state in the initial stages of the
      observation period. This lack of appearance of the Behavioural Satiety Sequence
      is more similar to a state of hyper-sedation than to DOI induced hyper-activity.
      The time course of this sedation would not have been picked up by a simple
      categorical analysis of behaviour. Hence, temporal analysis is an essential tool
      in understanding of drug induced anorexia.

PMID- 8981606
TI  - Dexmedetomidine reduces response tendency, but not accuracy of rats in attention
      and short-term memory tasks.
AB  - The present study investigated the role of alpha 2-adrenergic mechanisms in the
      performance of motor responses, attention and short-term memory in rats. A low
      dose (3.0 micrograms/kg, s.c.) of dexmedetomidine, an alpha 2-adrenoceptor
      agonist, reduced response tendency in an attentional task and a working memory
      task, but it did not affect the choice accuracy of rats. Atipamezole (300
      micrograms/kg), an alpha 2-adrenoceptor antagonist, increased anticipatory
      responding. Although atipamezole did not affect the number of omissions, it
      reversed the effects of dexmedetomidine on that parameter. We also investigated
      the effects of dexmedetomidine in rats with partial destruction of noradrenergic
      nerves induced by the neurotoxin DSP-4 (N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine hydrochloride). On its own, DSP-4 treatment did not affect
      choice accuracy or behavioural activity of rats in the attentional task. The
      effects of dexmedetomidine (0.3-3.0 micrograms/kg) on anticipatory responses did
      not differ between controls and DSP-4 group. Furthermore, the effect on omissions
      was not consistently diminished in DSP-4 treated rats. These results suggest that
      the activation of postsynaptic alpha 2-adrenoreceptors may be responsible for
      dexmedetomidine-induced reduction of response tendency while attention and short
      term memory are not markedly affected.

PMID- 8981608
TI  - Changes in the structure of the agonistic behavior of mice produced by D
      amphetamine.
AB  - The effects of three acute doses of D-amphetamine (0.25, 1.5 and 3 mg/kg) were
      studied in a model of isolation-induced aggression in male mice. An
      ethopharmacological analysis of the encounters was carried out, which studied the
      frequency, total and mean duration of different behavioral categories, including
      the temporal distribution of attacks and the duration of inter-attack intervals.
      The results show a reduction in the total and mean duration of the Attack
      category and an increase in motor activity manifested by longer durations, both
      total and mean, of Non Social Exploration and shorter Immobility. The temporal
      analysis of Attack revealed an increase in the number of very short (< 15 s)
      inter-attack intervals and a temporal redistribution of the attacks to later in
      the course of the social encounters. These results confirm for a complex behavior
      such as aggression, that D-amphetamine, even at low doses, favors a fragmentation
      and repetition of motor routines with a simultaneous reduction in the influence
      of environmental cues on the control of behavior.

PMID- 8981609
TI  - Effects of L-NOARG on plus-maze performance in rats.
AB  - Nitric oxide (NO) synthase, the enzyme responsible for NO formation, is located
      in brain regions such as amygdala and dorsolateral central grey, regions which
      are known to be involved in anxiety. To investigate the possible role of NO in
      anxiety, rats received acute i.p. injections of NG-nitro-l-arginine (L-NOARG, 7.5
      120 mg kg-1), an inhibitor of NO synthase, and were tested in the elevated plus
      maze, an animal model of anxiety. The drug, at doses of 30-120 mg kg-1, decreased
      the percentage of entries and time spent on the open arms of the maze, but these
      doses, with exception of 30 mg, also decreased the number of entries into
      enclosed arms. These effects disappeared when the animals were tested after
      chronic L-NOARG treatment (3.75 to 60 mg kg-1 i.p., twice a day for four days).
      The effects of acute i.p. injection of 30 mg kg-1 of L-NOARG were blocked by
      i.c.v. pretreatment with 1000 nmol of l-arginine (but not 500 nmol). Thus,
      inhibition of NO formation in the central nervous system seems to decrease
      exploration of the elevated plus maze, an effect that disappears after four days
      of chronic (twice a day) L-NOARG administration.

PMID- 8981610
TI  - Sex and genotype determine the selective activation of neurochemically-distinct
      mechanisms of swim stress-induced analgesia.
AB  - A growing literature documents the important influence of organismic factors such
      as sex and genotype on pain sensitivity and pain modulation. We recently
      determined that 3-min forced swims in 15 degrees C water produce non-opioid
      (i.e., naloxone-insensitive) analgesia in outbred Swiss-Webster mice of both
      sexes; this form of stress-induced analgesia (SIA) is significantly attenuated by
      the N-methyl-D-aspartate (NMDA) antagonist, dizocilpine (MK-801) in males, but
      not females. A pilot study designed to confirm the non-opioid and (in male mice)
      NMDAergic nature of 15 degrees C swim SIA in the C57BL/6J and DBA/2J inbred
      strains used widely in gene mapping was conducted, using the hot-plate (54
      degrees C) assay of nociception. In female mice of both strains, 15 degrees C
      swim SIA was insensitive to antagonism by either naloxone (10 mg/kg, i.p.) or
      dizocilpine (0.1 mg/kg. i.p.). In male C57BL/ 6J mice, the observed SIA was
      naloxone-insensitive, but was attenuated by dizocilpine. This pattern of results
      is virtually identical to that obtained using Swiss-Webster mice in this and
      previous studies. However, male DBA/2J mice displayed SIA that was significantly
      attenuated by naloxone, but insensitive to dizocilpine antagonism. These findings
      support the hypothesis that genetic factors and sex, in addition to stressor
      parameters, can determine the selective recruitment of alternative central
      mechanisms of pain inhibition.

PMID- 8981611
TI  - Effects of sodium azide on motor activity, motor coordination, and learning.
AB  - Because of the proposed importance of cytochrome oxidase in some neurological
      disorders, an inhibitor of this enzyme was evaluated in a battery of tests
      measuring exploration, motor coordination, and learning. Mice injected with
      sodium azide (6 or 12 mg/kg) were slower to initiate a response in a T maze and
      had less rears in a small chamber than mice injected with placebo. Drugged mice
      did not alternate spontaneously even at a minimal retention interval (0 min), but
      were not impaired in water maze spatial and visual discrimination learning tasks.
      No group differences emerged in terms of horizontal motor activity and its
      habituation, number of grooming episodes, and motor coordination. These results
      indicate that azide-induced slowing of motor activity is situation-specific and
      is accompanied by abnormalities in choice behavior in a T maze.

PMID- 8981613
TI  - Nitric oxide synthase inhibition impairs delayed recall in mature monkeys.
AB  - The gaseous neuromodulator nitric oxide (NO) is formed in brain regions known to
      mediate learning and memory processes. In rodent models, pharmacologic inhibition
      of NO synthesis impairs such processes. In the present study, N omega-nitro-L
      arginine methyl ester (L-Name), an inhibitor of the constitutive form of the NO
      synthetic enzyme, was administered to seven non-aged, mature monkeys (Macaca
      Fascicularis, Macaca Mulatta, and Macaca Nemestrima) trained to perform a delayed
      matching-to-sample task (DMTS). L-Name (1.5, 25, and 50 mg/kg) produced marked
      decrements in task performance, as well as a reduction in the number of trials
      completed at the highest dose. This impairment of DMTS accuracy by the 50 mg/kg
      doses of L-Name appears to be associated with an aversive state marked by
      gastrointestinal disturbance and lethargy. The detrimental effects of the 25
      mg/kg dose of L-Name on DMTS accuracy were completely blocked by concurrent
      administration of a mole-equivalent dose of the NO amino acid precursor L
      arginine. As a whole, these data suggest that L-Name impairs processes involved
      in delayed recall in monkeys and that this impairment is associated with
      attenuated synthesis of NO. However, at higher doses (> or = 25 mg/kg) this
      impairment is associated with aversive effects of L-Name, possibly at both
      central and peripheral sites.

PMID- 8981612
TI  - Effects of dynorphin A (1-13) on carbon monoxide-induced delayed amnesia in mice.
AB  - The effects of dynorphin A (1-13) on carbon monoxide (CO)-induced amnesia in mice
      were investigated. Memory deficiency was apparent during Y-maze testing 5 days
      after CO exposure (delayed amnesia). Percent alternation in the CO-exposed group
      was significantly lower than that in the control group. Administration of
      dynorphin A (1-13) (1.5 nmol, i.c.v.) 15 min before the Y-maze test session
      reversed the impairment of spontaneous alternation performance in the CO-exposed
      group. To determine whether this effect was mediated via kappa opioid receptors,
      we attempted to block the effect of dynorphin A using the kappa opioid receptor
      antagonist nor-binaltorphimine. Nor-binaltorphimine (5.44 nmol, i.c.v.) blocked
      the effect of dynorphin A (1-13) on delayed amnesia. Dynorphin A (1-13) did not
      affect the impairment of alternation induced by the blockade of NMDA-receptors by
      dizocilpine (MK-801), but significantly prevented the impairment induced by
      mecamylamine. These results suggest that dynorphin A (1-13) modulates the kappa
      receptor-mediated opioid neuronal system, and reverses the impairment of
      spontaneous alternation performance induced by CO exposure.

PMID- 8981614
TI  - Drug-drug discrimination: stimulus properties of drugs of abuse upon a
      serotonergic-dopaminergic continuum.
AB  - Ten male N/Nih rats were trained to discriminate between the interoceptive cues
      produced by the purportedly dopaminergically-mediated drug d-amphetamine at 0.4
      mg/kg intraperitoneally administered 20 min prior to training and those produced
      by the purportedly serotonergically-active agent norfenfluramine at 0.7 mg/kg.
      Once this discrimination was successfully acquired, the rats were tested with
      saline and with both drugs administered simultaneously and these manipulations
      were seen to produce random responding; indicating roughly equivalent cueing
      strength. Subsequently, various drugs thought to act upon serotonergic neurons,
      i.e., LSD and MDMA, were tested and shown to generalize in a dose-responsive
      manner to the norfenfluramine-appropriate lever. In contrast, the
      dopaminergically-active agent methcathinone and the D3 agonist 7-OH-DPAT produced
      generalization on the amphetamine-appropriate lever. Results are discussed in
      light of the increased specificity of behavioral testing available in a drug vs.
      drug discriminative paradigm using two drugs with different mechanisms of action.

PMID- 8981615
TI  - Intrahippocampal injections of phencyclidine but not naloxone disrupt acquisition
      of a spatial continuous recognition memory task.
AB  - Rats with 36 nM or 54 nM of phencyclidine (PCP), 36 nM of naloxone or saline
      injected into the dentate gyrus of the hippocampus were tested for acquisition of
      a spatial continuous recognition memory task. Results indicate that relative to
      controls and rats with 36 nM of PCP or 36 nM of naloxone injections, rats with 54
      nM of PCP injections were impaired in acquisition of the task across all lags as
      measured by increased in latency for repeated items. Since it is assumed that
      successful learning of this continuous recognition memory task depends upon
      processes associated with consolidation of new learning into long term memory, it
      appears that high doses of PCP, but not naloxone are sufficient to impair this
      process.

PMID- 8981616
TI  - Metrifonate treatment enhances acquisition of eyeblink conditioning in aging
      rabbits.
AB  - The cholinergic system is known to show deterioration during aging and
      Alzheimer's disease. In response, a therapeutic approach to Alzheimer's disease
      has been to attempt to compensate for the decrease in central cholinergic
      function by potentiating the activity of the remaining intact cholinergic cells
      with cholinesterase inhibitors. In this study treatment with the long-lasting
      cholinesterase inhibitor metrifonate enhanced acquisition of eyeblink
      conditioning in aging rabbits without producing interfering side effects. The
      effects of metrifonate on central and peripheral cholinesterase activity were
      evaluated, as was the involvement of plasma atropine esterase activity on the
      central and peripheral response to metrifonate. Results demonstrate that
      metrifonate can produce predictable, dose-dependent ChE inhibition. Associative
      learning in the aging rabbit was improved by metrifonate-induced steady state ChE
      inhibition within a range of 30-80%. Metrifonate was behaviorally effective in
      the absence of the severe side effects which typically plague cholinesterase
      inhibitors, suggesting that metrifonate is a possible treatment for the cognitive
      deficits resulting from normal aging and Alzheimer's disease.

PMID- 8981617
TI  - 8-OH-DPAT and male rat sexual behavior: partial blockade by noradrenergic lesion
      and sexual exhaustion.
AB  - As previously shown, the 5-HT1A agonist 8-OH-DPAT is a potent facilitator of male
      rat copulatory behavior in both sexually experienced and sexually exhausted male
      rats. The basis of this facilitation is still not clear. Therefore, the purpose
      of the present study was to determine whether 8-OH-DPAT-induced sexual-behavior
      facilitation could be counteracted by lesioning the NA system with the
      noradrenergic neurotoxin DSP4. In NA-lesioned, sexually experienced, non
      exhausted rats, the facilitatory effects of 8-OH-DPAT on the number of mounts and
      the postejaculatory interval were reduced, the effect on the intromission latency
      disappeared, while the percentage of copulating rats was not significantly
      altered. In sexually exhausted rats bearing a lesion of the NA system, the
      facilitatory effects of 8-OH-DPAT on the percentage of copulating rats was
      blocked. Data are discussed on the basis of the interactions between the
      noradrenergic and serotonergic systems in the mediation of the facilitatory
      effect of 8-OH-DPAT in sexually exhausted and non-exhausted rats.

PMID- 8981618
TI  - Effects of chronic lead exposure on cocaine-induced disturbance of fixed-interval
      behavior.
AB  - Chronic lead exposure has been shown to attenuate cocaine-induced increases in
      extracellular dopamine levels in the region of the nucleus accumbens, and
      antagonize the locomotor stimulating effects of the drug. The purpose of this
      study was to determine if similar lead-induced disturbances in the effects of
      cocaine include the impact of the drug on schedule-controlled responding. Adult
      male rats exposed ad libitum to water containing 500 ppm lead acetate (Group
      Lead), or a comparable concentration of sodium acetate (Group Control), were
      placed on a restricted diet (12-15 g food/day) prior to commencing fixed-interval
      (F1-5 min) schedule training on Day 33 of exposure. After 27 days of operant
      training, animals received a sequence of no injection, saline injection, and
      cocaine injection tests, repeating the sequence for 3, 10, 20 and 40 mg/kg
      cocaine HCl (i.p.). Local rates were determined for successive 30 s segments of
      the interval and the pattern of responding was compared under conditions of
      saline and cocaine injection. For both groups, cocaine increased responding,
      especially early in the interval. However, the rate enhancing effects of cocaine
      were less pronounced in lead-exposed animals than controls, at least at the 20
      mg/kg dose. These data extend earlier findings and accent the need to examine
      further the interactive relations between the external chemical environment and
      drug sensitivity.

PMID- 8981619
TI  - Amylin and food intake in mice: effects on motivation to eat and mechanism of
      action.
AB  - Amylin is a hormone produced by the pancreatic islets of Langerhans. Amylin
      decreased food pellet consumption. Amylin also decreased lever pressing for milk
      solution whether or not the mice were prefed. Amylin did not produce a
      conditioned taste aversion in a two bottle test, whereas lithium chloride did. In
      addition, L-arginine, a precursor for nitric oxide synthesis, was demonstrated to
      inhibit the ability of amylin to decrease food intake. Amylin did not alter
      nitric oxide synthase activity in the fundus of the stomach. These studies
      demonstrated that amylin inhibits food intake at a higher range of doses than is
      typical of anorectic agents such as cholecystokinin. Amylin does not appear to
      decrease food intake by reducing the release of nitric oxide but may affect
      appetite by modulating serum glucose levels when co-released with insulin.

PMID- 8981621
TI  - Behavioral comparison of the oximes TMB-4, 2-PAM, and HI-6 in rats using operant
      conditioning.
AB  - It has recently been shown that oximes can amplify the ability of cholinesterases
      to scavenge organophosphorus (OP) agents. Since both OP agents and oximes can
      disrupt performance, behavioral evaluation of bioscavenger therapies using oximes
      can be hindered. Therefore, we investigated the ability of three oximes,
      administered alone, to disrupt performance. The effects of trimedoxime bromide
      (TMB-4) (3.16-56.2 mg/kg), pralidoxime chloride (2-PAM) (10.0-237.1 mg/kg), and,
      1-([[4-amincarbonyl)pyridino]-methoxy]-methyl)-2, 4-bis[(hydroxyimino)methyl]
      pyridinium dichloride monohydrate (HI-6) (10.0-237.1 mg/kg) were evaluated in
      rats using a variable-interval 56 (VI 56) s schedule of food reinforcement. Under
      control conditions, the VI 56 s schedule produced a constant rate of responding
      (i.e., lever-pressing). All three oximes produced dose-dependent decreases in
      responding, and the largest doses of TMB-4 and 2-PAM produced complete or nearly
      complete suppression of responding in all rats. Only the largest dose of HI-6
      suppressed responding. Analysis of the dose-effect functions demonstrated that
      TMB-4 was substantially more potent than 2-PAM, which was slightly more potent
      than HI-6, for producing response suppression. These results establish doses of
      each oxime that will not contribute to disruption of responding, and thus,
      facilitate future evaluation of bioscavenger therapies against OP toxicity.

PMID- 8981620
TI  - Antidepressant-like effect of brain-derived neurotrophic factor (BDNF).
AB  - Previous studies have shown that infusion of brain-derived neurotrophic factor
      (BDNF) into the midbrain, near the PAG and dorsal/median raphe nuclei, produced
      analgesia and increased activity in monoaminergic systems. Alterations in
      monoaminergic activity have also been implicated in the pathogenesis and
      treatment of depression. The present studies examined the ability of centrally
      administered BDNF to produce antidepressant-like activity in two animal models of
      depression, learned helplessness following exposure to inescapable shock and the
      forced swim test. In the learned helplessness paradigm, vehicle-infused rats pre
      exposed to inescapable shock (veh/shock) showed severe impairments in escape
      behavior during subsequent conditioned avoidance trials, including a 47% decrease
      in the number of escapes and a 5 fold increase in escape latency, as compared to
      vehicle-infused rats which received no pre-shock treatment (veh/no shock).
      Midbrain BDNF infusion (12-24 micrograms/day) reversed these deficits, and in
      fact, BDNF-infused rats pre-exposed to inescapable shock (BDNF/shock) showed
      escape latencies similar to veh/no shock and BDNF/no shock rats. In the forced
      swim test, BDNF infusion decreased the immobility time by 70% as compared to
      vehicle-infused controls. Non-specific increases in activity could not account
      for these effects since general locomotor activity of BDNF- and vehicle-infused
      animals was not different. These findings demonstrate an antidepressant-like
      property of BDNF in two animal models of depression, which may be mediated by
      increased activity in monoaminergic systems.

PMID- 8981622
TI  - The non-competitive NMDA antagonist MK-801 increases food intake in rats.
AB  - A role for excitatory amino acids in the control of feeding behavior has not been
      extensively investigated. Nevertheless, there is direct and circumstantial
      evidence to indicate that some circuits involved with feeding behavior include
      glutamatergic elements. To test the hypothesis that endogenous glutamate
      participates in the control of food intake, we performed experiments to determine
      whether MK-801, a non-competitive N-methyl-D-aspartate (NMDA) ion channel
      antagonist, is capable of altering intake of liquid and solid foods in hungry or
      satiated rats. Following a 16 h fast, intake of 15% sucrose was significantly
      enhanced by systemic treatment with MK-801. Water intake was not altered by the
      NMDA antagonist. Rats did not ingest more rat chow after MK-801, unless they had
      been fasted. When a more palatable food (cookies) was offered, MK-801 did
      increase intake. Thus MK-801 enhanced food intake only when feeding was initiated
      by food-deprivation or increased palatability. In conclusion, our results support
      the hypothesis that endogenous glutamate plays a role in the control of food
      intake. Blockade of NMDA receptor function by MK-801 may diminish or delay
      satiety signals, rather than initiate feeding behavior per se.

PMID- 8981623
TI  - Serum anticholinergic activity and behavior following atropine sulfate
      administration in the rat.
AB  - Anticholinergic agents such as atropine and scopolamine have long been suggested
      to produce delirium-like states in humans and experimental animals. Evidence for
      an anticholinergic mechanism in the pathogenesis of human delirium has
      accumulated, leading to studies of the behavioral effects of the anticholinergic
      drug atropine in animals. The current study addresses the adequacy of animal
      models of delirium in terms of sensitivity, specificity and pharmacological
      relevance. A multiple fixed-ratio fixed-interval reinforcement schedule was used
      to test the effects of relatively low doses of atropine on behavior in rats.
      Additionally, total serum anticholinergic activity (SAA) was measured under dose
      and time course conditions identical to those used in the behavioral study.
      Atropine reduced high and low rates of responding in a dose-dependent manner, and
      SAA increased in a dose dependent manner. SAA at atropine doses of 0.1 mg/kg to
      1.0 mg/kg was similar to that found in delirious humans. These behavioral and
      serum level data suggest that relatively low doses of atropine, substantially
      below those used in previous attempts to model delirium using rats, may be more
      pharmacologically relevant to delirium and may minimize non-specific peripheral
      effects of this drug.

PMID- 8981624
TI  - Growth and behavioral effects of early postnatal chromium and manganese exposure
      in herring gull (larus argentatus) chicks.

PMID- 8981625
TI  - Effect of membrane lipid alteration on the growth, phospholipase C activity and G
      protein of HT-29 tumor cells.
AB  - The objective of the present study was to examine the effect of modifying the
      fatty acid composition of membranes on cell growth and phosphoinositide specific
      phospholipase C (PLC) activity in HT-29 colon cancer cells. Cells were seeded at
      a density of 12 x 10(3) cells/cm2 and supplemented with 30 microM of either 18:0,
      18:2 (n6) or 18:3 (n3) complexed to bovine serum albumin (BSA) in DMEM medium.
      Cell growth was followed for 12 days. The 18:0 supplemented cells (control)
      reached maximum growth at day nine which was greater than either 18:2 (n6) or
      18:3 (n3) supplemented cells. There was no difference between the latter two
      groups in their growth. To investigate the fatty acid incorporation of the
      supplemented fatty acid and how they may influence composition in the cell
      membrane, we examined the fatty acid composition of each phospholipid (PL)
      species. Both phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were
      significantly influenced by the type of fatty acid supplemented. Supplementation
      with 18:0 resulted in HT-29 cell membranes having more monounsaturated fatty
      acids than the cells grown in the other fatty acids. Polyunsaturated fatty acid
      (PUFA) supplementation (both 18:2 and 18:3) resulted in the enrichment of PUFA in
      the PL fractions. Cells supplemented with 18:3 (n3) had the highest unsaturation
      index in membrane PE as compared to the other phospholipid species. PLC activity
      of the membranes was measured using PIP2 as a substrate in the presence of 15
      micrograms alamethicin and 42 microM free calcium. The contribution of G protein
      to the activity of the enzyme was assessed using GTP gamma(S). PLC activity of HT
      29 cells was 16% higher in the presence of GTP gamma(S) response. GTP gamma(S)
      activated PLC activity of 18:3 (n3) supplemented cells was 81% of those
      supplemented with either 18:0 or 18:2 (n6) cells. It is concluded that the
      decrease in cell proliferation with supplementation with 18:3 (n3) may be
      mediated through its inhibitory effect on PLC, which provides the second
      messengers for protein kinase C (PKC) activation. PLC may be influenced by an
      increased unsaturation index of the PE fraction of the HT-29 tumor cell
      membranes.

PMID- 8981626
TI  - Prostaglandins in selected reproductive tissues in preterm and full-term
      gestations.
AB  - We investigated differences in maternal plasma and trophoblast prostaglandin
      metabolism associated with preterm births. Tissue prostaglandins (PGs) E2 and F2
      alpha and the stable plasma PGF2 alpha metabolite, 13,14-dihydro-15-keto-PGF2
      alpha, were measured in preterm (< 37 weeks) and term (< or = 37 weeks) births.
      Amnion PGE2 in preterm (106.1 +/- 15.7 ng/g wet weight tissue; x +/- SEM; n = 37)
      was lower than in term (176.6 +/- 22.7 ng/g wet weight; x +/- SEM; n = 34, P <
      0.02). Placenta PGE2 was lower in preterm (34.7 +/- 19.7 ng/g wet weight; x +/-
      SEM) than in term (103.3 +/- 28.0 ng/g wet weight; x +/- SEM, P < 0.04). Preterm
      PGF2 alpha was consistently lower in the amnion (106.8 +/- 17.5 ng/g wet weight)
      and placenta (102.5 +/- 8.7 ng/g wet weight) than in term amnion (188.2 +/- 24.8
      ng/g wet weight; P < 0.01) and placenta (128.9 +/- 7.8 ng/g wet weight; P <
      0.03). Chorionic PGE2 and plasma PGF2 alpha metabolite followed this trend but
      did not reach significance. These findings suggest qualitative and quantitative
      differences in maternal and trophoblast eicosanoid metabolism between term and
      preterm parturition.

PMID- 8981627
TI  - Endothelin-induced prostacyclin production in rat aortic rings is mediated by
      protein kinase C.
AB  - Endothelin (ET) is a vasoconstrictor peptide released from endothelial cells that
      is known to cause prostaglandin release. The mechanism remains unclear. To
      determine whether the protein kinase C (PKC) signaling pathway is stimulated by
      endothelin, we pretreated rat aortic rings with either PKC activator or
      inhibitors and measured the release of prostacyclin (PGI2) by radioimmunoassay.
      ET (10(-9) M) produced a 10-fold increase in PGI2 release. Pretreatment with 10(
      9) M of three different PKC inhibitors, 1-(5-isoquinolinesulfonyl)piperazine(CL),
      staurosporine, and 1-(5-isoquinolinesulfonyltmethyl)piperazine (H7), blocked ET
      induced PGI2 release. ET-induced PGI2 release was also blocked by pretreatment
      with inhibitors of either phospholipase A2 7,7-dimethyleicosadienoic acid or
      trifluoromethyl ketone analogue) (10(-9) M) or cyclooxygenase (indomethacin) (10(
      9) M). We conclude that ET activates PKC, which activates phospholipase A2, which
      liberates arachidonic acid, which increases PGI2 production and release.

PMID- 8981628
TI  - Metabolism of [3H]arachidonic acid by n-3 polyunsaturated fatty acid-enriched
      piglet alveolar macrophages.
AB  - The metabolism of [3H]arachidonic acid (3H-AA) by control and omega-3
      polyunsaturated fatty acid (n-3 PUFA)-enriched piglet alveolar macrophages (AM)
      was studied after a 4 and 24 h labeling period. 3H-AA metabolites were separated
      by gradient HPLC. Incorporation of exogenous 3H-AA for either 4 or 24 h was
      similar for n-3 PUFA-enriched AM compared with control AM. Calcium ionophore
      (A23187, 10 microM) stimulated a greater release of 3H-AA from n-3 PUFA-enriched
      AM compared with control AM. Furthermore, AM labeled for 24 h had a lower
      spontaneous release and higher stimulated release than those labeled for only 4
      h. The major 3H-AA metabolites detected in AM supernatants were PGF2 alpha, LTB4,
      and 5-HETE. Significant amounts of 3H-PGE2 were observed in the supernatants of
      those cells labeled for 24 h, but not 4 h. The absence of 3H-TXB2 was notable,
      since enzyme immunoassay detected significant quantities of this AA metabolite in
      all of the stimulated cell supernatants. From these data we conclude that n-3
      PUFA enrichment of piglet AM alters the metabolism of recently incorporated 3H-AA
      and that the metabolism of labeled AA may not parallel endogenous AA.

PMID- 8981629
TI  - Effect of diets containing different amounts of precursor and derivative fatty
      acids on serum TXB2.
AB  - Dietary precursor and derivative polyunsaturated fatty acids influence metabolic
      parameters, such as eicosanoid synthesis. We have studied the effect of dietary
      intakes of lipids containing different amounts of precursor and derivative fatty
      acids (olive oil, olive-blackcurrant-fish oil mixture, blackcurrant-fish oil
      mixture, MCT (medium chain triglycerides)-soyabean oil mixture) on serum
      thromboxane B2 (TXB2) in four groups of rats. Plasma fatty acid composition
      showed differences related to dietary intakes. TXB2 levels were similar in all
      conditions except in the group receiving the mixture of olive-blackcurrant-fish
      oils which showed lower values.

PMID- 8981630
TI  - Regulatory effects of dietary n-3 and n-6 lipids on plasma and hepatic lipid
      levels, liver cell number and microsomal protein content in spontaneously
      hypertensive rats.
AB  - Weanling male spontaneously hypertensive rats were fed semipurified diets
      containing either corn or fish oil for 8 weeks. Rats fed on fish oil diet had
      significantly lower plasma triglyceride, total cholesterol and HDL-cholesterol
      levels than rats fed on corn oil diet (P < 0.05). Moreover, rats fed on fish oil
      diet had significantly lower liver total lipid and triglyceride concentrations
      than rats fed on corn oil diet (P < 0.05). Dietary lipids were reflected in
      plasma fatty acid composition. Rats fed on fish oil diet had significantly
      greater plasma eicosapentaenoate (EPA) and docosahexaenoate (DHA) (n-3 PUFAs)
      with an accompanying decrease in plasma linoleate (LA) and arachidonate (AA) (n-6
      PUFAs), in comparison with the rats fed corn oil (P < 0.05). Those results would
      suggest that the n-3 PUFAs were incorporated into plasma lipids at the expense of
      the n-6 PUFAs. Rats fed on corn oil diet had significantly greater liver DNA
      content than rats fed on fish oil diet (P < 0.05), thereby implying that the n-3
      PUFAs in fish oil had an inhibitory effect on liver cell proliferation.
      Furthermore, rats fed on fish oil diet had significantly greater hepatic
      microsomal protein content than rats fed on corn oil diet (P < 0.05), indicating
      that fish oil exerted a stimulatory effect on hepatic microsomal enzymes.

PMID- 8981631
TI  - Bile but not chyle lipoprotein is an important source of arachidonic acid for the
      rat small intestine.
AB  - Arachidonic acid (AA) functions as a structural component, eicosanoid precursor
      and surface material for chylomicron production in the gastrointestinal tract.
      The origin of this AA is poorly characterized. [3H]AA labelled chylomicrons and
      [14C]AA albumin-FFA were injected intravenously into biliary diverted rats and
      controls. Radioactivity in tissue lipids was measured after different time
      intervals. Output of 3H and 14C in bile was 8% of the injected dose during 24 h.
      Radioactivity of the upper small intestine but not of colon and stomach increased
      with time. Bile drain reduced the recovered amounts of radioactivity in upper
      small intestine by 75% after 24 h. In stomach and colon 3H/g tissue was 16-20
      fold lower than in liver after 24 h. Recovery of 3H in liver was higher than of
      14C. In liver 3H/g tissue was 15-40 fold higher than in stomach and colon after
      10-60 min. Equilibration between AA pools of liver and other organs was not
      complete after 96 h. Biliary phospholipid is an important source of AA for the
      small intestine.

PMID- 8981632
TI  - Stimulation of proliferation of an essential fatty acid-deficient fish cell line
      by C20 and C22 polyunsaturated fatty acids and effects on fatty acid composition.
AB  - Recently we reported the development of a fish cell line, EPC-EFAD, derived from
      the carp (Cyprinus carpio) epithelial papilloma line, EPC, that could survive and
      proliferate in essential fatty acid-deficient (EFAD) medium. The EPC-EFAD cell
      line may be a useful model system in which to study the cellular biochemical
      effects of EFA deficiency and has advantages in studies of polyunsaturated fatty
      acid (PUFA) and eicosanoid metabolism in fish in that the complications
      introduced by culture in relatively n-6 PUFA-rich mammalian sera are removed. In
      the present study, the effects on cell proliferation rate of supplementing EPC
      EFAD cells with various n-3 and n-6 PUFA were investigated to determine the
      possible role(s) of PUFA in cell growth and division. The selectivity of
      incorporation of specific PUFA into individual glycerophospholipid classes and
      the feasibility of reproducing in vivo fatty acid compositions in vitro were also
      investigated. Proliferation of the EPC-EFAD cell line was stimulated by
      arachidonic (20:4 n-6), eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n
      3) fatty acids but not by 18:2 n-6 or 18:3 n-3. The differential effects of PUFA
      on cellular proliferation may be related to the lack of significant delta 5
      desaturase activity in the cells at 22 degrees C and may implicate a role for
      eicosanoids in the mechanism of stimulation of proliferation. PUFA
      supplementation increased the cytotoxic effects of longer term culture, an effect
      that was partly alleviated by inclusion of vitamin E in the culture medium. The
      cells could generally be supplemented with PUFA to produce cellular fatty acid
      compositions in vitro that were similar to in vivo compositions.

PMID- 8981633
TI  - Okadaic acid enhances prostaglandin E1-induced alkaline phosphatase activity in
      osteoblast-like cells: regulation at a point downstream from protein kinase A.
AB  - We examined the effect of okadaic acid, an inhibitor of protein phosphatase type
      1 and 2A, on prostaglandin E1 (PGE1)-induced alkaline phosphatase (ALP) activity
      in osteoblast-like MC3T3-E1 cells. PGE1 increased ALP activity dose dependently
      in the range between 10 nM and 0.3 microM in these cells. The pretreatment with
      okadaic acid enhanced the PGE1-induced ALP activity in a dose-dependent manner in
      the range between 0.1 and 5 nM. On the other hand, 1-norokadaone, a less potent
      analogue of okadaic acid, had no effect on the PGE1-induced ALP activity.
      Tautomycin, an another inhibitor of protein phosphatase type 1 and 2A, also
      enhanced the PGE1-induced ALP activity. PGE1 stimulated cAMP accumulation dose
      dependently in the range between 10 nM and 0.3 microM. However, PGE1 had no
      effect on the formation of inositol phosphates. Okadaic acid did not affect the
      PGE1-induced cAMP accumulation. Okadaic acid dose dependently enhanced the
      dibutyryl cAMP-induced ALP activity. These results strongly suggest that protein
      phosphatase type 1 and/or 2A act as a regulator of ALP activity at a point
      downstream from protein kinase A in osteoblast-like cells.

PMID- 8981634
TI  - Is a (n inborn) deficiency of prostacyclin synthesis stimulating plasma factor
      associated with increased lipoprotein(a)?
AB  - Patients with the antiphospholipid syndrome as well as those with a lack in the
      prostacyclin synthesis stimulating plasma factor (PF) are prone to develop
      thrombophilia and are at a higher clinical risk for vascular disease. As patients
      with the antiphospholipid syndrome have been reported to show elevated
      lipoprotein (Lp)(a) levels, we re-examined all our patients known to have an
      inborn or an acquired persistent deficiency of PF. Their non-affected relatives
      served as controls. In addition, 36 patients suffering from clinically manifested
      atherosclerosis as well as 16 healthy adults, all of them having elevated Lp(a)
      levels (> 30 mg/dl), were screened for a PF deficiency. In fact, all the patients
      with a deficient PF activity showed elevated Lp(a) values. While the prevalence
      of PF deficiency ranges about 1-2%, in 7 (19%) patients with clinically
      manifested atherosclerosis and 3 (19%) healthy adults with elevated Lp(a) this
      defect was found. The findings demonstrate an association between PF deficiency
      and Lp(a), indicating a biochemical interaction which needs to be further
      elucidated.

PMID- 8981635
TI  - Effect of ewe and lamb genotype on gestation length, lambing ease and neonatal
      behaviour of lambs.
AB  - To distinguish between ewe and lamb breed effects on prenatal growth, ease of
      parturition and early lamb behaviour, an embryo-transfer study was carried out
      using a hill breed (Scottish Blackface; liveweight: 54.25 +/- 1.03 kg, mean +/-
      s.e.m.) and a lowland breed (Suffolk; 80.33 +/- 1.52 kg) to obtain the four
      possible combinations of ewe and lamb. Data were collected from 38 Blackface ewes
      (18 with Blackface lambs and 20 with Suffolk lambs) and 41 Suffolk ewes (20 with
      Blackface lambs and 21 with Suffolk lambs); all ewes were given single embryos.
      Suffolk lambs had a significantly longer gestation than Blackface lambs (1.5
      days, P < 0.01), regardless of ewe breed. Suffolk lambs also had a longer labour
      (20 min, P < 0.05) and were significantly more likely to require birth assistance
      (17/21, 81% of all assisted deliveries; P < 0.001), as were male lambs (19/21,
      90%; P < 0.01). These variables were independent of ewe breed. Blackface lambs
      were significantly more active than Suffolk lambs in the first 2 h after birth;
      ewe breed had little effect on lamb behaviour. Blackface lambs stood twice as
      quickly as Suffolk lambs after birth (13 min v. 24 min; P < 0.001), and were
      significantly more likely to suckle within the first 2 h after birth (92% v. 66%;
      P < 0.05). The behavioural retardation of Suffolk lambs may be a consequence of
      their birth difficulty which increases their likelihood of suffering birth trauma
      and hypoxia at parturition. Together, these factors may increase the probability
      of neonatal death in these lambs.

PMID- 8981636
TI  - Aldosterone release from adrenal cells is inhibited by reduced oxygen levels in
      vitro during maturation in rabbits.
AB  - Hypoxia in vivo leads to a decrease in aldosterone not completely explained by
      extrinsic controllers of adrenal function including adrenocorticotrophic hormone,
      renin-angiotensin II, and K+. The dissociation of renin and aldosterone during
      acute hypoxia in vivo may be explained by the finding that aldosterone synthesis
      in adrenal cells is reversibly and specifically inhibited by decreases in O2
      levels within the physiological range. The present study investigated whether the
      direct effect of acute decreases in O2 levels on aldosteronogenic pathway is
      altered during maturation. Adrenal cells (whole adrenals) were prepared from
      fetal (27 days gestation), neonatal (1 day), and infant (10 days) New Zealand
      White rabbits, and capsular cells were prepared from young (21 days) and adult (3
      months) rabbits. All cells were dispersed with collagenase. Basal and cAMP
      stimulated aldosterone production were assessed under two different levels of O2
      (pO2 = 20.0 kPa or pO2 = 8.7 kPa). Decreased O2 levels significantly inhibited
      cAMP-stimulated aldosterone production in cells obtained from rabbits of all ages
      by 60 +/- 5% cAMP-stimulated aldosterone production was significantly lower in
      cells obtained from neonates and premature animals under both normoxic and
      reduced O2 conditions as compared with animals > or = 10 days old. Corticosterone
      production by cells obtained from adults and 21-day-old rabbits was unaffected by
      reduced O2 conditions suggesting a specific effect on the aldosterone pathway.
      The data demonstrate that the O2 sensitivity of the aldosterone pathway is
      present throughout development.

PMID- 8981637
TI  - High concentrations of immunoreactive inhibin in the plasma of mares and fetal
      gonads during the second half of pregnancy.
AB  - Plasma concentrations of immunoreactive (ir)-inhibin were measured in seven
      pregnant mares from around Day 140 of gestation to Day 2 after parturition using
      a heterologous bovine-based radioimmunoassay (RIA). Concentrations of luteinizing
      hormone (LH), follicle-stimulating hormone (FSH), oestradiol-17 beta,
      progesterone and relaxin were also measured in the same samples. A marked
      increase in plasma concentrations of ir-inhibin, FSH and LH occurred between Day
      220 and Day 300 of gestation but the concentrations of all three hormones
      returned to baseline by about Day 320 (three weeks before parturition). In
      contrast, circulating concentrations of the three placental hormones, oestradiol
      17 beta, progesterone and relaxin, increased during the final weeks of pregnancy
      and then decreased markedly to basal values within two days of parturition. There
      was a positive correlation between circulating concentrations of ir-inhibin and
      FSH (r = 0.75, P < 0.01) rather than the expected negative correlation. ir
      inhibin was not detected in homogenates obtained at Day 190 of pregnancy and form
      term placenta, but high concentrations of ir-inhibin were present in homogenates
      of fetal and newborn gonads. Despite the high concentrations of ir-inhibin in
      these homogenates, they failed to exert any suppressive bioactivity on FSH
      secretion by rat pituitary cells cultured in vitro. Furthermore,
      immunohistochemical staining revealed the presence of inhibin in the interstitial
      cells of equine fetal gonads at Day 190 of gestation. These findings demonstrate
      for the first time that high concentrations of ir-inhibin, LH and FSH are
      secreted into the peripheral circulation of the mare during the second half of
      pregnancy. However, ir-inhibin present in the plasma of pregnant mares appears to
      be biologically inactive. This hormone is not presumed to be of placental origin
      but it is proposed that either the enlarged fetal gonads or the maternal ovaries,
      or both of these organs, may be a source of inhibin in response to the coincident
      increase in circulating concentrations of LH and FSH.

PMID- 8981638
TI  - Stimulation of Ca2+ current by phorbol esters in rat myometrial cells is
      dependent on intracellular Ca2+ concentration.
AB  - The effects of phorbol esters on the L-type Ca2+ current (ICa(L)) were
      investigated using nystatin-perforated patch and standard whole-cell voltage
      clamp in uterine smooth muscle cells isolated from late-pregnant rats. Using
      nystatin-perforated patch to maintain the integrity of the cytosol components,
      phorbol 12-myristate 13-acetate (PMA, 300 nM) increased ICa(L). When the standard
      whole-cell voltage clamp was used, the effect of PMA was dependent on the Ca2+
      concentration in the pipette solution: PMA enhanced ICa(L) at pCa 6 and pCa 7 but
      not at pCa 10 or pCa 8. The effect of PMA was reversed by a selective inhibitor
      of protein kinase C, calphostin-C (500 nM). It is concluded that phorbol esters
      stimulate ICa(L) in uterine muscle cells and that the isoform of protein kinase C
      involved in this effect is Ca2+ dependent. This mechanism may be involved in the
      regulation of uterine contraction during pregnancy.

PMID- 8981639
TI  - Effect of culture conditions on artificial activation of porcine oocytes matured
      in vitro.
AB  - The effects of culture media used and culture period for in vitro maturation of
      porcine oocytes on their subsequent response to chemical and electrical
      activation, were investigated. Activated oocytes were identified by the presence
      of a pronucleus(ei) or cleavage. Porcine oocytes were cultured for 24, 30, 36, 42
      and 48 h in TCM199 with Earle's salts (199) supplemented with 10% fetal calf
      serum (199-FCS) before electrical stimulation. Although few oocytes were
      activated after 24 h and 30 h of culture (5.4% and 6.1% respectively), the
      percentage of activated oocytes increased significantly to 93.2% after 42 h in
      culture (P < 0.05); however, when the culture period was extended to 48 h, there
      was a significant decrease to 56.7% (P < 0.05). Oocytes were also cultured in
      four types of media: (1) 199-FCS; (2) 199 supplemented with 5 mg mL-1 bovine
      serum albumin (199-BSA); (3) Kreb's-Ringer bicarbonate solution supplemented with
      10% FCS (KRB-FCS); and (4) KRB supplemented with BSA (KRB-BSA). After 42 h of
      culture in each medium, the oocytes were electrically activated. Although rates
      of maturation of oocytes cultured in the four media were similar (74.0-80.8%),
      all oocytes except those cultured in 199-FCS failed to be activated. In addition,
      oocytes were cultured for 36, 42 and 48 h in 199-FCS and then stimulated by
      treatment with ethanol. Significantly fewer oocytes were activated in the
      chemically-treated group than in the electrically-treated group. These results
      indicate that culture conditions used for the culture of porcine oocytes in vitro
      are important with respect to their subsequent response to artificial activation.

PMID- 8981640
TI  - Evidence against a significant role for mast cells in blastocyst implantation in
      the rat and mouse.
AB  - Rats were treated with the highly potent stabilizer of mast cells, FPL 55618,
      before and during the first seven days of pregnancy to establish whether
      stabilization of mast cells resulted in impaired blastocyst implantation. There
      was no significant reduction in either the number of ovulations or the number of
      implantation sites in treated rats compared with controls; 11 of 15 treated rats
      were pregnant compared with 5 of 6 control rats. The distribution of mast cells
      was examined in uterine tissues, implantation sites and interimplantation sites
      in both rats and mice using highly sensitive immunohistochemical techniques.
      Virtually all of the mast cells in rat uterine tissue stained for rat mast cell
      protease-I (RMCP-I; connective tissue type), whereas few stained for RMCP-II
      (mucosal type). Most of the mast cells were present in the myometrium with very
      sparse distribution in the endometrium and there were no differences in numbers
      of mast cells between implantation and inter-implantation sites on Day 7 of
      pregnancy. In tissue sections of mouse uteri sampled from Day 1 to Day 8 of
      pregnancy there were virtually no mast cells in the endometrium or deciduum
      adjacent to implantation sites. Mouse uterine mast cells also stained
      predominantly for the connective tissue-type mast cell protease MMCP-4, the
      murine equivalent of RMCP-I. Thus, mast cells and their products appear to play
      little, if any, role in blastocyst implantation in murid rodents. Since mast
      cells are a prominent feature of human endometrium, this study emphasizes the
      important consideration of species differences when choosing animal models for
      implantation studies.

PMID- 8981641
TI  - Viability and membrane integrity of spermatozoa after dilution and flow
      cytometric sorting in the presence or absence of seminal plasma.
AB  - Boar, bull and ram spermatozoa were examined after staining with the DNA-permeant
      Hoechst 33342 fluorochrome and flow cytometric sorting in the presence or absence
      of seminal plasma. Spermatozoa were assessed for viability with flow cytometry
      using the live cell nucleic acid stain SYBR-14 and propidium iodide (PI), and for
      membrane integrity using fluorescein isothiocyanate-conjugated Pisum sativum
      (FITC-PSA) and PI; motility and acrosome integrity were estimated by microscopy.
      Flow cytometric sorting was compared with pipette dilution of boar and bull
      spermatozoa into: (1) medium [boar: Test buffer containing 2% yolk (TY) or
      Beltsville thawing solution (BTS); bull: TY or HEPES buffer containing 0.1%
      bovine serum albumin (HEPES-BSA)] with or without 10% (v/v) seminal plasma; or
      (2) an empty tube containing no medium. Sorted spermatozoa were either not
      centrifuged or centrifuged before assessment during a 4-h holding period. The
      viability, motility and membrane integrity of boar, bull and ram spermatozoa
      centrifuged after sorting were also examined when seminal plasma was present or
      absent from the staining extender and/or the TY collection medium. The results
      indicate that the viability and membrane integrity of spermatozoa in vitro would
      be improved if: (1) seminal plasma (10%) was routinely included in the BTS and
      HEPES-BSA staining extenders for boar spermatozoa and ram spermatozoa,
      respectively, when used in preparation for flow cytometric sorting; and (2) 10%
      and 50% seminal plasma were included in the TY collection medium for boar or bull
      spermatozoa and ram spermatozoa respectively.

PMID- 8981642
TI  - Activity of aspartate aminotransferase and acid phosphatase in cryopreserved
      trout sperm.
AB  - Milt of brown, rainbow and brook trout was cryopreserved. Activity of aspartate
      aminotransferase (AspAT) and acid phosphatase was assayed both in supernatants
      and in spermatozoa obtained from thawed sperm samples; additionally, post-thaw
      motility was evaluated. Enzyme activities differed according to fish species and
      were strongly affected by the type of cryoprotectant used. The activity in
      supernatants was usually higher than that in spermatozoa because of protein
      leakage from injured cells. AspAT activity in cryopreserved spermatozoa
      correlated positively with fertilization success in all three species. There was
      a negative correlation between activity of extracellular (supernatant) AspAT and
      fertilization rates in variants with dimethyl sulfoxide and dimethylacetamide
      based extenders. The motility of thawed sperm, determined microscopically,
      provided some information on the cryopreservation efficiency of trout milt.

PMID- 8981643
TI  - Anti-fertility effects of oral medroxyprogesterone acetate in rabbits.
AB  - Studies on the anti-fertility effects of medroxyprogesterone acetate (MPA) were
      conducted in rabbits. The bioavailability of MPA and plasma concentrations of
      progesterone and luteinizing hormone (LH) after mating were monitored following a
      single meal containing MPA (1000 mg) in entire does (n = 4); the response to
      gonadotrophin-releasing hormone (GnRH; 250 ng) was also observed in MPA-treated,
      ovariectomized does (n = 6). The reproductive tracts of rabbits mated following
      MPA treatment were examined 28-30 h after mating. Another group of rabbits (n =
      4) received a single dose of MPA on Days 1, 10 or 19 after mating or daily for
      five days from Day 24. After dosage with 1000 mg MPA, plasma concentrations of
      MPA were detectable for eight days. However, following multiple dosing (10 mg, 5
      days) MPA was detectable in the plasma for two days. MPA reduced the rate of
      ovulation and suppressed the increase in plasma concentrations of progesterone
      and LH observed after mating for four days, but had no effect on the response to
      GnRH. When administered late in gestation, MPA caused the death of fetuses. These
      results demonstrate an inhibitory effect of MPA on ovulation, probably at the
      hypothalamic level, and impairment of gestation or parturition.

PMID- 8981644
TI  - Defects in the allocation of cells to the inner cell mass and trophectoderm of
      parthenogenetic mouse blastocysts.
AB  - Diploid parthenogenetic mouse embryos (which possess two maternally-derived
      genomes) can develop only as far as the 25-somite stage when transferred in utero
      and exhibit a substantial reduction in trophoblast tissue. The loss of cultured
      parthenogenetic embryos during postimplantation indicates that a defect in cell
      lineage may be evident as early as the blastocyst stage. The possibility that a
      defect may already be reflected at the preimplantation stage was investigated by
      examining the allocation of cells to the trophectoderm (trophoblast progenitor
      cells) and the inner cell mass of haploid and diploid parthenogenetic mouse
      blastocysts. Utilizing a differential labelling technique for counting cells,
      diploid parthenogenetic blastocysts were found to have fewer inner cell mass
      cells and trophectoderm cells than their haploid counterparts and normal
      blastocysts. In addition, both haploid and diploid parthenogenetic blastocysts
      had a lower inner cell mass: trophectoderm ratio than normal blastocysts. Thus,
      the relatively poor development of the trophectoderm lineage at the
      postimplantation stage is not reflected by a reduction in its allotment of cells
      at its first appearance. Nevertheless, the findings indicate that parthenogenetic
      development is already compromised at the blastocyst stage, and provide evidence
      that the expression of imprinted genes has significance for the development of
      the embryo at the preimplantation stage.

PMID- 8981645
TI  - Roles of growth factors in the development of bovine embryos fertilized in vitro
      and cultured singly in a defined medium.
AB  - Bovine embryos at the 8- or 16-cell stage were cultured singly, or in groups (10
      12 embryos), in the presence or absence of bovine oviduct epithelial cells (BOEC)
      in a defined medium which was used as a basic culture medium. A higher (P < 0.05)
      proportion of 8-cell embryos (48.3-50.8%) cultured singly developed beyond the 8
      cell stage after the addition of platelet-derived growth factor (PDGF)-AB (1 ng
      mL-1) only, or with PDGF-AB + basic fibroblast growth factor (bFGF; 1 ng ml-1) +
      transforming growth factor (TGF)-beta 1 beta 2 (1 ng mL-1) than in basic medium
      alone (30.3%). In contrast, a significantly (P < 0.02) higher percentage (62.6
      65.8%) of 16-cell embryos developed to the morula stage after the addition of TGF
      beta 1 beta 2 only, or the addition of TGF-beta 1 beta 2 + bFGF + PDGF-AB than in
      basic medium alone (30.2%). These proportions were not significantly (P > 0.05)
      different from the proportions obtained when embryos were cultured in groups, but
      were significantly (P < 0.005) lower than the proportions obtained when embryos
      were cultured in groups on BOEC monolayers. Arachidonic acid (50 ng mL-1), beta
      mercaptoethanol (10 microM) and glutathione (10-1000 microM) stimulated the
      development of 8-cell embryos in the presence of PDGF and TGF-beta 1 beta 2;
      blastocyst formation was observed for the first time in 8-cell embryos cultured
      singly in the presence of these embryotrophic substances (2.2-6.2%).

PMID- 8981647
TI  - Oestrous synchronization, semen preservation and artificial insemination in the
      Mohor gazelle (Gazella dama mhorr) for the establishment of a genome resource
      bank programme.
AB  - Gazella dama mhorr is an endangered species with an extant population of about
      190 animals distributed between several zoos. Semen was collected by electro
      ejaculation from 12 adult males, and cryopreserved in TEST-yolk diluent
      containing 6% glycerol. The effects of the concentration of egg yolk (5%, 10% and
      20%) and the presence or absence of sodium triethanolamine lauryl sulfate (equex)
      on sperm motion and acrosomal integrity after thawing were examined. Increasing
      concentrations of egg yolk resulted in more acrosomal damage and poorer motility
      after thawing. The presence or absence of equex had no effect on either
      parameter. The frozen spermatozoa were used in an insemination trial, in which 13
      females were treated with intravaginal progesterone-releasing devices to
      synchronize oestrus. Seven females were inseminated with frozen-thawed semen 48 h
      after removal of the devices, and six were inseminated after 60 h. Three females
      in the first group and one in the second group became pregnant. However, only one
      pregnancy (from the 48-h group) was carried to term. The study demonstrated the
      feasibility of applying artificial insemination in this species, but revealed
      that a number of outstanding technical problems remain to be solved.

PMID- 8981646
TI  - Expression of oncofetal fibronectin in porcine conceptuses and uterus throughout
      gestation.
AB  - Oncofetal fibronectin is reportedly expressed specifically by trophoblast tissue
      and some tumours and speculated to mediate placental attachment. In the present
      study, a monoclonal antibody (FDC-6) to human oncofetal fibronectin was used to
      characterize temporal and spatial changes in the expression of oncofetal
      fibronectin at the fetal-maternal interface of pigs. Conceptus and uterine
      tissues were collected from gilts throughout normal pregnancy and processed for
      immunohistochemical characterization. Results indicated that oncofetal
      fibronectin was constitutively expressed by both porcine conceptus and uterus
      throughout gestation. The most abundant staining for oncofetal fibronectin was
      found in the allantochorion and detectable levels of oncofetal fibronectin were
      also detected in luminal and glandular epithelial cells in the uterus. During the
      second-half of pregnancy, oncofetal fibronectin was also detected in fibroblast
      like cells in the uterine stroma, but not in the stroma of the allantochorion.
      Owing to the non-invasive nature of the porcine placenta, the abundant expression
      of oncofetal fibronectin by the trophoblast and uterus may influence attachment
      between chorion and endometrium during pregnancy. Since attachment is the first
      step in implantation and placentation in all mammalian species, the pig may
      represent an excellent animal model to study interactions between trophoblast and
      endometrium mediated by oncofetal fibronectin.

PMID- 8981648
TI  - [Clinical study of occupational uroepithelial cancer].
AB  - We studied 438 persons who were engaged in the production and use of aromatic
      amines (benzidine sulfate, beta-naphthylamine, alpha-naphthylamine and
      dianisidine). Among these 438 persons, 88 new cases of occupational uroepithelial
      cancer had occurred from 1949 to 1995. The incident rate of occupational
      uroepithelial cancer was 20.1%. The average exposure period of these 88 cases to
      the aromatic amines was 7.40 years (range, 0.75-26.75), and the incidence rate of
      tumors increased with the length of exposure to aromatic amines. The average
      latent period was 26.79 years (range, 1.33-48.50), and the average age of first
      onset was 52.59 (range, 24-79). Recently it has been determined that the longer
      the latent period, the older the age of first onset. Of these 88 cases, the tumor
      sites were bladder in 67 cases (76.1%) and upper urinary tract (renal pelvis
      and/or ureter) in 5 cases (5.7%). The other 16 cases (18.2%) were the bladder and
      upper urinary tract. The screening examination for chemical workers using urinary
      cytology was begun in 1962. In our cases, urine cytology was a useful method for
      diagnosing occupational uroepithelial cancer. As for initial treatment of the 88
      cases, transurethral surgery was most frequently performed, that is on 58 cases
      (65.9%). However, eight cases (9.1%) had to undergo a total nephroureterectomy,
      and six cases (6.8%) had a total cystectomy. Recurrence was observed in 61 cases
      (69.3%) out of the 88 patients with an average of 1.81 times. The other organic
      cancers developed in 39 cases (8.9%) out of 438 workers who were exposed to
      aromatic amines and in 8 cases out of 88 patients (9.1%). Prognosis of the 88
      patients is that, the number of alive and dead is 51 (58.0%) and 37 (42.0%)
      respectively on December 31, 1995. Twenty-eight patients (31.8%) died of
      uroepithelial cancer, and five patients (5.7%) died of other organic cancers. The
      survival rates of 5, 10, 15 and 20 years was 87.9%, 74.0%, 65.9% and 56.3%,
      respectively. From these results, patients with occupational uroepithelial cancer
      and workers who are exposed to aromatic amines should undergo long term
      observation.

PMID- 8981650
TI  - [Estimation and control measures for environmental tobacco smoke in an office].
AB  - The aim of this study is to evaluate the air pollution due to smoking in an
      office where no smoking control measures have been adopted. The concentration of
      suspended particulates (SP) at 8 points in this office were measured and the
      change of SP concentrations at 3 points were recorded for 24 hours. The results
      show that the main source of SP is tobacco smoke in the office. Smoking control
      measures should be promoted in such offices where smokers and non-smokers work
      together. The effectiveness of a ventilation system and practical smoking control
      measures are discussed.

PMID- 8981651
TI  - [Isolation of endothelial cells from human umbilical cords and development of low
      cost culture medium].
AB  - To study the role of endothelial cells in important biological phenomena such as
      thrombosis and atherosclerosis, it is necessary to have a sufficient amount of
      endothelial cells. This report shows modified methods to isolate endothelial
      cells from the human umbilical vein and the components of potent and low-cost
      culture medium for the cells.

PMID- 8981649
TI  - [The effect of brain-derived neurotrophic factor on regeneration of nerve fibers
      after crush injury--morphometric evaluation].
AB  - Brain-derived neurotrophic factor (BDNF) is produced in Schwann cells and
      fibroblasts in the peripheral nerve, and is considered to play an important role
      in survival, maintenance, development and repair of the peripheral neuron. In
      this study, the effect of human recombinant BDNF on the regeneration of nerve
      fibers following a crush injury to the sciatic nerves of Sprague-Dawley rats was
      evaluated. In the experimental group, 20 mg/kg of BDNF was injected
      subcutaneously three times a week for 4 weeks in seven rats. In the control
      group, only the dissolving solution used in the experimental group was injected
      similarly in seven rats as in the experimental group. The various morphometric
      parameters were evaluated in the peroneal, sural and tibial nerves and the nerve
      to soleus muscle distal to the crush site. There were no statistically
      significant differences in the change of body weight, the improvement of the
      width between the first and fifth toes on the side of the crush, the density of
      total myelinated fibers (numbers per mm2), the total number of myelinated fibers
      (number per nerve), maximum and median diameters of myelinated fibers, the
      density of unmyelinated fibers, and the electron microscopic parameters of axon
      and myelin sheath. On the other hand, the number of myelin lamellae in relation
      to the transverse axonal area was significantly greater in the experimental group
      than in the control group. Therefore, BDNF may promote the myelination. However,
      such an effect on myelination seems not to be clinically significant, because
      such an effect was not demonstrated in other morphometric evaluations reflecting
      the myelination condition. Therefore, taking all the data obtained in this study
      into consideration, we concluded that there was no definite evidence that BDNF
      promoted the regeneration of nerve fibers at least under these experimental
      conditions.

PMID- 8981652
TI  - Nitric oxide as a challenge for the clinical chemistry laboratory.
AB  - Nitric oxide (NO) is an important intra- and intercellular mediator. Although NO
      can be measured using many different chemical methods, the compound is
      challenging for a clinical chemistry laboratory, since its half-life in vivo in
      humans is only a few seconds. Most of the NO is oxidized to nitrite/nitrate, and
      the concentrations of these anions have been used as quantitative indices of NO
      production. The simplest and most widely used technique is spectrophotometric
      measurement of nitrite using the Griess reaction. Nitrate, the main metabolite of
      NO in blood and urine, must be reduced to nitrite before the colour reaction.
      Other methods used for measuring nitrite/nitrate in human blood or urine include
      high-performance liquid chromatography, gas chromatography-mass spectrometry,
      chemiluminescence, enzymatic assay with nitrate reductase and electron
      paramagnetic resonance. The reported mean concentrations of nitrite in the blood
      of healthy adults have varied from non-existent to 4.2 mumol l-1, and those of
      nitrate from 19.7 to 44 mumol l-1. The technical measurement of nitrite/nitrate
      is obviously reliable, but there are problematic preanalytical factors. Normal
      daily food contains more nitrate than that formed from NO, and thus diet-derived
      nitrate may contribute considerably to the concentration in blood. The problem
      may to some extent be solved with dietary restrictions, but it is questionable
      whether the confounding effect of diet-derived nitrate can be totally avoided.
      Therefore, better methods for measuring the production of NO in vivo would be
      very welcome.

PMID- 8981653
TI  - The effect of brief illumination on intracellular free calcium concentration in
      cells with 5-aminolevulinic acid-induced protoporphyrin IX synthesis.
AB  - The effect of illumination on intracellular free calcium concentration, [Ca2+]i,
      was studied in a cell line (WiDr cells) derived from a primary adenocarcinoma of
      the rectosigmoid colon. In these cells the biosynthesis of protoporphyrin IX was
      stimulated by 5-aminolevulinic acid to reach levels of 600-700 pmol of
      protoporphyrin IX per mg cell protein. A brief (1-min) exposure of the cells to
      light (70% of light energy at 340-380 nm) resulted in an increase in [Ca2+]i.
      This increase was not reversible over a period of at least 20 min following
      illumination. Elevation of [Ca2+]i most probably represented an influx of calcium
      ions from the medium to the cell, since it was completely abolished in the
      presence of extracellular EGTA. The increased [Ca2+]i did not reflect general
      membrane damage, as determined by trypan blue staining as well as measurement of
      the intercalation of ethidium bromide into cellular DNA, and neither did the
      sustained elevation of [Ca2+]i lead to any substantial loss of clonogenicity
      following illumination of protoporphyrin-containing cells. Together these results
      indicate that an increased [Ca2+]i level is not per se a cause of cell death
      during photodynamic therapy.

PMID- 8981654
TI  - An evaluation of the Ektachem serum lithium method and comparison with flame
      emission spectrometry.
AB  - We evaluated the performance of a new colorimetric method in dry chemistry for
      serum lithium (Li) assay using an Ektachem E500 analyser. Imprecision results
      were acceptable and the linearity was verified for concentrations within the
      range of 0.2-3.9 mmol l-1, i.e. y(measured) = 1.02x(calculated) + 0.07, r = 0.99.
      The Ektachem Li assay was unaffected by potassium (K), calcium (Ca) and magnesium
      (Mg) at all concentrations tested. Significant interference was caused by sodium
      (Na) and haemoglobin. Statistically and clinically significant interference was
      caused by high concentrations of Na (213 mmol l-1) with a bias of 0.20 mmol l-1
      (p = 0.02) and by high levels of haemoglobin (280 mumol l-1) with a bias of 0.20
      mmol l-1 (p = 0.01). Comparison of serum Li results from 80 patient samples
      assayed using the Ektachem method with those obtained using the IL943, a flame
      atomic emission spectrometry (FAES)-based method, gave a regression line
      equation: Ektachem = 0.95xFAES + 0.13, r = 0.96. The data revealed a mean
      difference of 0.10 mmol l-1 between the Ektachem and FAES results that was
      statistically significant (p = 0.01), but clinically negligible. We conclude that
      the Kodak method provides reliable Li serum results and represents a valid
      alternative to the FAES method.

PMID- 8981655
TI  - Immunochemical and functional properties of biliary alpha-1-antitrypsin.
AB  - Alpha-1-antitrypsin (AAT), the archetype of the serpin (serine proteinase
      inhibitor) superfamily, is synthesized by hepatocytes and excreted to some extent
      into bile. The role of intact biliary AAT in gallstone pathogenesis is unsettled,
      but its 36-residue C-terminal peptide was found to promote cholesterol
      crystallization in a bile model. The present study showed biliary AAT to have
      specific properties that differ from serum AAT regarding immunoreactivity, heat
      stability and antiproteolytical activity. Electrophoretical and immunochemical
      methods were used to characterize biliary AAT. The level of its inhibitory
      activity was determined spectrophotometrically. In 18 samples from common bile
      duct and 12 samples from gallbladder bile, AAT was found to be heat-stable and
      functionally inactive. Added to the untreated, temperature-inactivated or
      protease inhibitors containing bile, native AAT became functionally inactive,
      heat-stable and lost its immunoreactivity. In contrast, heat-inactivated AAT,
      native albumin, transferrin, alpha-1-antichymotrypsin and IgG were unaffected on
      being added to bile. AAT in human bile manifests specific biochemical properties,
      such as functional inactivity and heat stability, that may be consistent with a
      conformational transition of the serpin molecule induced by the hydrophobic
      environment, and which must be considered when evaluating its role in gallstone
      pathogenesis.

PMID- 8981656
TI  - Analysis of clobazam and its active metabolite norclobazam in plasma and serum
      using HPLC/DAD.
AB  - This report describes a simple reversed-phase high-performance liquid
      chromatographic (HPLC) method with automated solid-phase extraction (SPE) for
      analysing clobazam and norclobazam concentrations in human serum or plasma. For
      the HPLC analysis the samples and standards are prepared with an ASPEC automatic
      sample preparer using 100-mg Bond-Elut C-18 solid-phase extraction columns. The
      HPLC method is an isocratic method with a mobile phase of
      acetonitrile:methanol:10 mmol l-1 dipotassium hydrogen phosphate, pH 3.7
      (30:2:100), at a flow rate of 1.5 ml min-1. The benzodiazepines are detected with
      a diode array detector (DAD) at 240 nm and the peak purity analyses are performed
      at 210-365 nm. The recovery is over 97% for both analytes, and it is independent
      of the drug concentration. The intra-assay CVs vary between 0.7 and 2.2% and
      inter-assay CVs between 3.8 and 4.6% at therapeutic drug concentrations. The
      detection limit is 15 nmol l-1. The assay is linear from 30 to 20,000 nmol l-1
      (clobazam) and from 170 to 105,000 nmol l-1 (norclobazam). This method leads to a
      very good separation of norclobazam from carbamazepine and phenytoin. None of the
      anti-epileptic or antidepressant drugs tested interfere with the assay.

PMID- 8981657
TI  - Comparison of body composition by dual energy X-ray absorptiometry to other
      estimates of body composition during weight loss in obese patients with
      rheumatoid arthritis.
AB  - Body composition was determined by dual energy X-ray absorptiometry (DXA)
      scanning and classical reference methods (40K, 3H2O, and a combination of these
      in a four-compartment model) in 19 overweight patients with rheumatoid arthritis
      who underwent a 12-week weight-reducing regimen. The aim of the study was to
      investigate whether DXA provides a valid estimate of body composition. The
      results showed that weight as determined by DXA was highly significantly
      correlated to weight determined by scales. Furthermore, significant correlations
      were found in the body components (fat-free mass, fat mass) determined by DXA,
      40K, 3H2O and the four-compartment model. Mean values differed slightly but
      significantly. With respect to changes in body composition, no significant
      correlations were found between any of the methods, except for the weight loss
      recorded by DXA and scales, and loss of fat mass (and fat free mass) estimated by
      3H2O and the four-compartment model. The sparseness of correlations reflected the
      small changes in fat-free mass and fat mass (2.6 and 1.7 kg respectively), and
      the fact that changes were comparable to measurement errors of the various
      methods. We suggest that DXA scanning is a valid supplement for determination of
      body composition. Validation of DXA scanning requires new experimental in vitro
      investigations, which, incidentally, also applies to the classical reference
      methods.

PMID- 8981658
TI  - Implications of automated creatine kinase (CK)-MM1,2,3/CK-MB1,2 isoform analysis
      as an early marker for the detection of myocardial tissue damage.
AB  - Measurement of creatine kinase (CK) isoforms enables the clinician to detect
      myocardial tissue damage at an early stage after myocardial infarction. According
      to the manufacturer's specifications, it should be possible to perform CK isoform
      analysis automatically using the new Cardio Rep analyser. In order to investigate
      the suitability of this new analyser we measured the CK MM1-3, and CK MB1 and 2
      isoform patterns, firstly in 30 patients with acute myocardial infarction (AMI),
      for whom total CK and CK-MB levels were ordered, and secondly in 23 patients with
      chest pain suspected as having AMI (n = 11) or with unstable angina pectoris
      (UAP) (n = 12). The total time for analysis, including 5 min pre- and 10 min post
      analyser run time, was found to be 40 min. For elevated MB2/MB1 ratios there is a
      discrepancy between the MB2/MB1 ratios determined from the densitometric scans
      concerning the surface and the peak height ratios. The MB2/MB1 ratios of the
      studied AMI patients exceeded the upper reference limits approximately 2 h after
      the onset of symptoms, whereas the CK-MB and total CK levels increased after
      about 6 h. The MB2/MB1 ratios from the patients with UAP were either below the
      detection limit or these patients could be discriminated from patients with AMI
      when low CK-MB and total CK levels were considered in conjunction. From our
      results we conclude that assessment of CK isoforms can be performed relatively
      simply with the new analyser within 40 min. However, for reliable calculation of
      the MB2/MB1 ratios, the curve monitoring of the MB2-MB1 densitometric scans
      should be improved. The CK isoforms are useful as an early marker for AMI as
      their reference interval is already exceeded approximately 2 h after an AMI.
      Moreover, CK isoform analysis might prove to be useful in discriminating at an
      early stage between AMI and other causes of chest pain. This could decrease the
      number of patients with a false-positive diagnosis admitted to coronary care
      units, resulting in a reduction of costs.

PMID- 8981659
TI  - Sex hormone responses in healthy men and male patients with chronic obstructive
      pulmonary disease during an oral glucose load.
AB  - The responses of serum testosterone, sex hormone-binding globulin (SHBG) and
      luteinizing hormone (LH) to an oral glucose tolerance test (OGTT) were
      investigated in 16 healthy subjects as well as in 11 normoxaemic and 10
      hypoxaemic chronic obstructive pulmonary disease (COPD) patients. The latter
      group were investigated on two occasions, with and without oxygen therapy.
      Testosterone and apparent free testosterone concentration (AFTC) fell
      significantly in the healthy subjects as well as in the hypoxaemic patients on
      oxygen therapy (p < 0.01), whereas LH increased in all groups during the OGTT (p
      < 0.05). There were significantly higher SHBG levels (p < 0.01), and lower AFTC
      levels (p < 0.05) in the hypoxaemic group compared to the healthy subjects. In
      the hypoxaemic group short-term oxygen therapy increased basal AFTC significantly
      (p < 0.05). With oxygen therapy, the 120-min glucose levels fell significantly
      from 9.1 +/- 3.2 to 7.6 +/- 2.7 mmol l-1 (mean +/- SD) in the hypoxaemic group (p
      < 0.05). In conclusion, we have found the serum testosterone and AFTC levels to
      decrease after an oral glucose load in healthy subjects, together with a
      compensatory increase in LH. The same pattern is seen in COPD patients. The
      hypoxaemic patients have a reduced AFTC which is partly reversed by oxygen
      therapy.

PMID- 8981661
TI  - Activation of FXII during haemodialysis.
AB  - This study was designed to provide information on the kinetics of FXIIa activity
      and C3d release during haemodialysis. Dialysis was performed twice in 9 stable
      patient for 240 min with the same conditions except for a change in dialysate
      sodium profile (using a linear sodium programme starting at 138 and ending at 148
      mmol/l or vice versa). Using paired statistics there was a significant (p < 0.02)
      increase in both C3d release and the FXIIa activity. The sodium profiles did not
      alter the outcome. The increase in FXIIa activity, which is maximal at the end of
      dialysis, is continuous, unlike the C3d release, which is maximal within 15 min
      of dialysis and then levels off. Both interactions are induced by the blood
      membrane contact. These results indicate that the FXIIa activation is not
      strictly coupled to the activation of the complement system.

PMID- 8981660
TI  - Clinical application of a novel DNA fluorescence intercalator, pyrylium dye, for
      the quantification of PCR products.
AB  - Polymerase chain reaction (PCR) is a powerful tool for clinical diagnosis in the
      field of oncology, infection, and allergy. However, a simple and sensitive method
      for quantifying PCR products has not been established. We therefore used a novel
      fluorescence DNA intercalator, pyrylium iodide (P2) to quantify PCR products. A
      838-bp fragment of the human beta-actin gene and a 374-bp fragment of the gene
      for ornithine decarboxylase (ODC) and ODC primer dimers were generated by PCR and
      quantified using either P2 or another fluorescence DNA intercalator, YOYO-1. In
      addition, utilizing RT-PCR and the P2 method, the ODC mRNA expression from 10
      colonic cancers was quantified. Serially diluted beta-actin and ODC PCR products
      could be quantified using P2 without having to separate them from primer dimers
      and other components of the reaction mixture. However, YOYO-1 could not be used
      to quantify the PCR products because of high background fluorescence from the
      primer dimers. In the clinical study, ODC mRNA expression as quantified by P2 was
      significantly higher in cancerous tissue (113.8 +/- 4.1; mean +/- SEM; plate
      reader units) than in mucosa of normal appearance (68.4 +/- 4.8). P2 is a
      promising tool for quantifying PCR products.

PMID- 8981662
TI  - Serum tumour-associated trypsin inhibitor (TATI) and renal function.
AB  - Tumour-associated trypsin inhibitor (TATI) is a low molecular weight (MW) protein
      employed as a tumour marker. The blood levels of some low MW proteins increase in
      renal insufficiency. The aim of this study is to evaluate the relationship
      between serum TATI and glomerular filtration rate (GFR). Serum beta 2
      microglobulin (beta 2M) and plasma creatinine were also determined. The decrease
      of GFR was accompanied by an increase in the other parameters. The maximum
      increase of TATI was from a mean basal value of 8.51 +/- 5.58 micrograms l-1 in
      subjects with normal renal function to 107.27 +/- 63.34 micrograms l-1 in
      patients with renal failure; beta 2M increased from 1.45 +/- 0.38 to 11.16 +/-
      5.73 mg l-1 and creatinine from 1.05 +/- 0.17 to 5.07 +/- 1.93 mg dl-1. The
      increase in TATI occurs sooner and is greater than that of beta 2M and of
      creatinine. These results suggest that TATI is handled by the kidney. It is
      sensitive marker of reduction in renal function. When TATI is used as a tumour
      marker, renal function must be taken into account in the evaluation of the
      results.

PMID- 8981663
TI  - Is nitric oxide and heparin treatment justified in inflammatory bowel disease? An
      experimental study.
AB  - Microcirculatory disturbances of the colon may contribute to the pathogenesis of
      inflammatory bowel disease. The aim of the study was to investigate the
      alterations of rectal blood perfusion in experimental colitis with reference to
      nitric oxide and heparin treatment. The study was carried out on 36 rats, divided
      into six groups: group I, control; group II, control + NG-nitro-L-arginine (L
      NNA); group III, colitis without treatment; group IV, colitis + L-arginine; group
      V, colitis + L-NNA; group VI, colitis + heparin treatment. Experimental colitis
      was induced by 4% acetic acid enema, and 48 h after the enema, besides the
      measurement of rectal capillary blood flow by means of laser Doppler flowmetry,
      the serum interleukin-6 (IL-6) level and histopathological alterations within the
      rectal mucosa were examined. Experimental colitis resulted in a drop in rectal
      wall perfusion. L-Arginine and heparin treatment improved the microcirculatory
      values. The highest IL-6 level and the most advanced histopathological
      alterations were observed in the rats treated with L-NNA. L-Arginine treatment
      had no influence on IL-6 concentration, however it aggravated the inflammatory
      changes within the rectal mucosa. Heparin administration reduced the IL-6 values
      and also had a positive impact on the microscopic alterations within the rectal
      wall. It is concluded that heparin treatment has a beneficial effect on the
      microcirculatory disturbances and inflammatory changes observed in experimental
      colitis. The inhibition of nitric oxide-synthase aggravated the course of
      experimental colitis. L-Arginine administration improves the rectal blood flow
      but aggravates the histopathological alterations within the rectal wall.

PMID- 8981664
TI  - Lack of inhibitory effect of atrial natriuretic factor on renin release induced
      by renal hypotension.
AB  - To examine the effect of atrial natriuretic factor (ANF) on renin release induced
      by renal hypotension, experiments were performed in seven
      barbiturateanaesthetized dogs with denervated kidneys. Renin release induced by
      renal arterial constriction to 55 mmHg was measured before and during intrarenal
      infusion of ANF (200 ng min-1 kg-1 body weight). Before ANF infusion, renal
      arterial constriction increased renin release from 0.2 +/- 0.1 to 21.8 +/- 3.3
      micrograms angiotensin I min-1 (p < 0.05). During ANF infusion renal arterial
      constriction increased renin release as much as before from 0.8 +/- 0.6 to 23.7
      +/- 4.6 micrograms angiotensin I min-1 (p < 0.05). Although ANF increased
      glomerular filtration rate from 33.9 +/- 4.2 to 43.4 +/- 5.6 ml min-1 (p < 0.05)
      and sodium excretion from 72 +/- 22 to 567 +/- 112 mumol min-1 (p < 0.05) at
      normal renal perfusion pressure, ANF was without effect on glomerular filtration
      rate and sodium excretion during renal arterial constriction. The present study
      shows that ANF is not an inhibitor of renin release induced by renal arterial
      constriction in anaesthetized dogs with denervated kidneys. Our findings indicate
      that ANF does not influence renin release induced by the haemodynamic mechanism.

PMID- 8981665
TI  - Novel pathways for elimination of cholesterol by extrahepatic formation of side
      chain oxidized oxysterols.
AB  - Recently, we described a new pathway whereby peripheral cells can eliminate
      intracellular cholesterol by conversion into the more polar oxysterols 27
      hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid. The latter steroids
      are easily excreted from the cells and transported to the liver for conversion
      into bile acids. Our attempts to evaluate the importance of this new mechanism
      are reviewed here and also our investigations on the possible presence of
      additional similar pathways for removal of extrahepatic cholesterol. Human
      alveolar macrophages in culture were shown to have a high capacity to convert
      cholesterol into 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid and
      to excrete these steroids into the culture medium. Treatment of the macrophages
      with cyclosporin A, an inhibitor of sterol 27-hydroxylase, reduced the excretion
      of the 27-hydroxylated products by more than 90%, with a concomitant accumulation
      of intracellular cholesterol. The quantitative importance of the mechanism in
      relation to reverse cholesterol transport was investigated in 14C-cholesterol
      labelled macrophages exposed to HDL. At very low concentrations of HDL, possibly
      similar to those present in tissues, the two pathways were about equally
      effective. At optimal concentrations of HDL, however, reverse cholesterol
      transport was about 10-fold more effective than the sterol 27-hydroxylase
      pathway. The net uptake of 27-oxygenated steroids by the liver was measured in
      volunteers by comparison of the levels in the hepatic vein with those in a
      peripheral artery. Approximately 20 mg of 27-oxygenated oxysterols was taken up
      by the liver during 24 hours. Quantitative conversion of these oxysterols into
      bile acids would correspond to 4% of the total bile acid formation. It is evident
      that this new pathway contributes significantly to cholesterol elimination. The
      possibility that the sterol 27-hydroxylase pathway is of importance for
      cholesterol homeostasis in the brain was investigated by measuring oxysterols in
      the internal jugular vein and in an artery of healthy volunteers. There was no
      net flux of 27-hydroxycholesterol from the brain into the circulation. There was,
      however, a significant flux of 24-hydroxycholesterol, corresponding to
      elimination of about 4 mg cholesterol/24 hours. This flux is higher than the
      estimated rate of synthesis of cholesterol in the human brain. To summarize, we
      have demonstrated two mechanisms for cholesterol elimination from extrahepatic
      cells by specific oxygenases capable of oxidizing the steroid side-chain. The
      efficiency of these mechanisms is based on the fact that side-chain hydroxylated
      cholesterol species are both translocated through lipophilic membranes and
      converted into bile acids at a much faster rate than cholesterol itself. The
      importance of the sterol 27-hydroxylase-mediated mechanism is illustrated by the
      fact that patients who lack this enzyme develop xanthomas and premature
      atherosclerosis in spite of normal levels of circulating cholesterol.

PMID- 8981666
TI  - Familial thrombophilia: clinical and molecular analysis of Swedish families with
      inherited resistance to activated protein C or protein S deficiency.
AB  - This report describes the characterization of Swedish families with inherited
      resistance to activated protein C (APC resistance) and/or protein S deficiency,
      two genetic disorders associated with functional impairment of the protein C
      anticoagulant pathway. The APC resistance phenotype was linked to the factor V
      gene locus in a kindred with independent inheritance of APC resistance and
      protein S deficiency. A point mutation changing Arg506 to a Gln (FV:Q506) in the
      factor V gene was the cause of APC resistance. In studies of 50 families with
      hereditary APC resistance, the FV:Q506 mutation was identified in 94% (47/50) of
      the families, and the thrombotic risk was found to be dependent on the factor V
      genotype. Moreover, 18 families with hereditary deficiency of free protein S were
      investigated. Type I protein S deficiency (low free and total protein S) and type
      III deficiency (low free but normal total protein S) coexisted in 78% (14/18) of
      the families, suggesting the two types to be phenotypic variants of the same
      genetic disorder. Deficiency of free protein S was caused by equimolar
      relationship between protein S and beta-chain containing isoforms of C4BP. Though
      protein S deficiency was a strong risk factor for thrombosis, the FV:Q506
      mutation was identified as an additional genetic risk factor in 39% of the
      families. Thus, familial thrombophilia is a multiple gene disorder. The
      thrombophilic tendency associated with APC resistance or protein S deficiency was
      related to increased levels of prothrombin fragment 1 + 2, reflecting increased
      activation of the common coagulation pathway.

PMID- 8981667
TI  - Molecular basis for amyloidosis related to hereditary brain hemorrhage.
AB  - The aim of the project has been to elucidate molecular events leading to
      amyloidosis in Hereditary Cystatin C Amyloid Angiopathy (HCCAA) patients, to
      enable simple diagnosis of the disease and with the ultimate goal to understand
      the amyloid formation process in detail, in order to develop inhibitors to the
      process. At the DNA level, a point mutation segregating with HCCAA was identified
      in the cystatin C gene on chromosome 20, after basic characterization of cDNA and
      gene for the wildtype protein. The mutation results in the amino acid
      substitution Leu-68-Gin (L68Q) and abolishes a recognition site for Alu I. This
      information was used to design a PCR based assay for simple and rapid mutation
      detection in DNA from blood samples to allow routine diagnosis of HCCAA. Studies
      at the protein level, allowed through E. coli expression of wildtype and L68Q
      mutated cystatin C genes, revealed that both protein variants effectively inhibit
      the cysteine proteinase cathepsin B (equilibrium constants for dissociation: 0.4
      and 0.3 nM, respectively), but differ considerably in their tendency to dimerize
      and form aggregates. The initial dimerization of L68Q-cystatin C results in
      complete loss of biological activity and is highly temperature-dependent, with a
      rise in incubation temperature from 37 to 40 degrees C resulting in a 150%
      increase in dimerization rate. This result might be of clinical relevance, since
      medical intervention to abort febrile periods of carriers of the disease trait
      may reduce the in vivo formation of L68Q-cystatin C aggregates. The three
      dimensional structure of normal cystatin C, crystallized in a complex with
      cathepsin B, was elucidated by X-ray analysis and subsequent refinement of the
      structure to 3.0 A resolution. Besides pinpointing the cystatin C structures
      resulting in efficient target enzyme inhibition, the results demonstrated that
      the Leu-68 residue is buried in the hydrophobic core of the protein. Studies of
      the three-dimensional solution structure of wildtype cystatin C by NMR
      spectroscopy revealed that cystatin C dimers can be formed as a result of slight,
      localized structural changes under conditions preceding complete defolding and
      denaturation of the protein. Dimers of L68Q-cystatin C are likely similar but are
      formed at temperatures nearly 30 degrees C lower than needed for the wildtype
      protein, indicating that the Leu-68-Gln substitution lowers the transition
      temperature for unfolding. Thus, the results presented suggest that cystatin C
      provides a system where decreased stability of a mutant protein correlates with
      its amyloidogenic nature. The NMR results furthermore imply that the hydrophobic
      proteinase-binding region of cystatin C is directly involved in dimer formation
      and that compounds designed to interact with this region could serve as
      inhibitors to the dimerization, and likely also the subsequent amyloid formation
      process, of cystatin C in HCCAA patients.

PMID- 8981668
TI  - Androgen receptor gene amplification: a novel molecular mechanism for endocrine
      therapy resistance in human prostate cancer.
AB  - Since the development and growth of the prostate cancer is highly dependent on
      androgens, androgen deprivation therapy continues to be the treatment of choice
      for patients with advanced prostate cancer. The therapy is very effective, but
      responses are often short-lived. We describe here a novel molecular mechanism
      that may explain why prostate cancer cells become resistant to hormonal therapy.
      Amplification of the androgen receptor (AR) gene was found to be selected for
      during androgen deprivation therapy in 23% of prostate cancer patients who
      experienced local tumor recurrence. Amplification leads to increased expression
      of the AR gene, which enables the cancer cells to more effectively utilize the
      residual low levels of androgens for sustaining cell growth. Discovery of AR
      amplification as a possible molecular mechanism of therapy resistance in prostate
      cancer should prove useful for development of more effective endocrine therapy
      regimens as well as diagnostic and predictive tests for therapy failure.

PMID- 8981669
TI  - A prospective cardiovascular population study used in genetic epidemiology. The
      Copenhagen City Heart Study.
AB  - Rapid advances in molecular biology will in the near future allow insight into
      which mutations are important for determining an individual's susceptibility to
      cardiovascular disease, as well as to other multifactorial diseases. Methods for
      diagnosing mutations are today easy to use; however, strategies for determining
      the effect of a given mutation on phenotype, as well as on the susceptibility of
      carriers to disease, are less well established. In the present paper, we describe
      a DNA bank, consisting of more than 10,000 individuals, which--for a given
      mutation--will allow us to determine its frequency in the general population, the
      effect of the mutation on phenotype, and its influence on the development of
      cardiovascular as well as other diseases.

PMID- 8981670
TI  - [The effect of interdependency on the levels of self and other perception].
AB  - This study investigated the possibility that different levels of self-other
      interdependency lead to different levels of self and other perception. Forty-six
      undergraduates were randomly assigned and were told descriptions of everyday
      relations that were either high or low in interdependency. They were asked
      whether they experienced each type of the relations, and if they did, what they
      thought for each at the time. Content analysis of their statements indicated that
      statements about intention, attitude, and emotion of self and other were more
      frequent when the interdependency was high than low, whereas statements
      disregarding intention and thought of self and other were more numerous at low
      interdependency. It is suggested that the levels of self and other perception are
      interrelated, and that the degree of interdependency between self and the other
      determines the salient level of self and other perception.

PMID- 8981671
TI  - [Reading ability of elementary school children: a componential analysis].
AB  - It was hypothesized that there are three independent levels of reading
      processing: Letter and word level, sentence level, and discourse level. Reading
      speed of 117 fifth-grade children were assessed, and clause length, position in
      each sentence, and position in passage were found to affect the speed
      independently. These features therefore must correspond respectively to the
      levels mentioned above. Since working memory capacity possibly determined the
      functioning of the three levels, reading span as the capacity was assessed in the
      study and incorporated into a multivariate path model, in order to predict
      ability in reading comprehension. The span and vocabulary explained the child's
      general reading ability. The ability together with domain specific knowledge
      explained the child's domain specific reading comprehension. Finally, the
      applicability of those findings to the programs to assist children who have
      difficulty in reading comprehension was discussed.

PMID- 8981672
TI  - [The availability of personality traits in the hierarchical structure: an
      exploration of the "basic level"].
AB  - Personality traits have a structure that is hierarchically organized in terms of
      trait abstractness. Which level of the hierarchy is most available to the person
      perceiver? We started out with four levels, and tried to determine which was most
      available and therefore became the "basic level", as in the Rosch, Mervis, Gray,
      Johnson, and Boyes-Braem's natural categories (1976). Two methods were employed.
      First, rating of trait descriptiveness showed that information effectiveness was
      relatively high at the second level from the top. Second, subjects preferred the
      same level when they described target persons. These results suggested that a
      "basic level" indeed existed in the hierarchy of personality traits. However,
      social desirability of traits and who the target person was also affected the
      results. Implications are discussed about theories of cognitive style, especially
      cognitive complexity, which assume the generality of our cognitive system and
      have been in confusion with contradictory findings.

PMID- 8981673
TI  - [Velocity perception for curved motion].
AB  - This study examined the effect of direction change of tangential velocity on
      speed perception using a dot in curved motion. The PSE values were measured for
      four standard stimuli of different motion curvature. In Experiment 1,
      semicircular motion was a comparison stimulus. The result showed that the PSE
      values increased with increasing motion curvature. This implies that direction
      change of tangential velocity can affect its speed perception. However, in
      Experiment 2, the effect of direction change of tangential velocity was not clear
      when a comparison stimulus was replaced with linear motion. In Experiment 3, the
      motion curvature as a comparison stimulus was set near the threshold level of
      curvature detection. As the result, the similar trend to Experiment 1 was
      observed. However, the effect of direction change of tangential velocity remained
      the same as Experiment 2. These results suggests that direction change of
      tangential velocity can affect its speed perception, while the effect depends on
      how much direction change of tangential velocity could be detected for a
      comparison stimulus.

PMID- 8981674
TI  - [Effects of the peripheral vision on visually induced vertigo].
AB  - Visually induced vertigo, or motion sickness, is thought to be mainly influenced
      by motion perception, not by shape perception. We examined this point by
      comparing the effect of the foveal vision on the visually induced vertigo with
      that of the peripheral vision. We set up three kinds of display conditions:
      Foveal vision (F), peripheral vision (P), and foveal + peripheral vision (F + P).
      Videotaped motion was presented on the display. The results showed that a
      drifting eye movement was larger after the experiment than before the experiment
      in the (P) and the (F + P) conditions, but not in the (F) condition. In addition,
      the mirror drawing was improved only in the (F) condition. Subjective ratings for
      the vertigo were higher in both the (P) and the (F + P) conditions than in the
      (F) condition. These results indicate that some visual units concerning low
      spatial frequencies participate in the visually induced vertigo.

PMID- 8981675
TI  - [Delays produced by prolonged viewing in the recognition of Kanji characters:
      analysis of the "Gestaltzerfall" phenomenon].
AB  - It is a well-known observation that when a Kanji character is viewed steadily and
      continuously, the viewer often becomes unable to recognize the Kanji as a whole
      pattern and it becomes difficult to judge whether or not the Kanji is
      orthographically correct. Such a phenomenon is called the "Gestaltzerfall" of
      Kanji characters. In the present study, two experiments were carried out to
      examine delays in the recognition of test Kanji following 25 s of prolonged
      viewing of adaptation Kanji, which were comprised of either the same or different
      parts and structures. When the size of the adaptation Kanji was equal to that of
      the test Kanji, there were significant delays of more than 50 ms, both when the
      stimuli were of the same pattern, and when they had the same structure but
      different components. However, when their sizes were different, delays were found
      only when the test and the adaptation Kanji were of the same pattern. These
      results suggest that a Kanji pattern may be internally represented as a whole,
      independent of its size, while the processing of Kanji structure may be dependent
      upon its size. Prolonged viewing may produce an adaptation effect specific to
      such representations.

PMID- 8981676
TI  - [The relation of age, gender and sex-role identity to role expectation in same
      sex friends].
AB  - The purpose of this study was to examine the relation of age, gender, and sex
      role identity to role expectation in same-sex friends (SSF). Role expectation in
      SSF consisted of ten categories (Wada, 1993): Cooperation, information,
      similarity, self-enhancement, sensitivity, companionship, authenticity, self
      disclosure, respect, and interdependence. Subjects were 129 (67 male and 62
      female) junior high school, 243 (118 male and 125 female) senior high school, and
      168 (88 male and 80 female) college students. Major findings were as follows:
      Senior high school and undergraduate students expected more self-enhancement from
      SSF than junior high students. Junior and senior high school students expected
      more companionship than undergraduates. Undergraduates expected more authenticity
      and less self-disclosure than junior high school students. And male students
      expected more companionship, information, and similarity, but less self
      disclosure, self-enhancement, and respect from SSF than female. Clear results of
      the relationship between sex-role identity and role expectation in SSF weren't
      found.

PMID- 8981677
TI  - A three-step procedure for assessing bioequivalence in the general mixed model
      framework.
AB  - Bioavailability data arising from a standard two-period cross-over study are
      routinely analysed to establish bioequivalence between test and reference
      formulations. Current regulatory guidelines only require evidence of equivalence
      in average bioavailability for the assessment of bioequivalence. Under normality
      assumptions, this is achieved by demonstrating equivalence between the
      formulation means (step 1). However, the equivalence of formulation variances
      should also be assessed to get evidence of population bioequivalence (step 2),
      since a difference in variability of bioavailability may also pose significant
      problems in drug safety and efficacy. On the other hand, even population
      bioequivalence does not ensure that an individual subject could be expected to
      respond similarly to the two formulations. Therefore, whenever individual
      bioequivalence is the ultimate goal, the magnitude of intra-subject correlation
      should always be examined as the final stage (step 3). In this paper, these three
      successive concepts of bioequivalence are cast into the general mixed model
      framework and a stepwise testing procedure for the global assessment of
      bioequivalence is proposed. In addition to this, important issues addressed in
      the regulatory guidelines, such as verification of the model assumptions and
      application of the log-transformation, are discussed. Lastly, an example is
      presented to illustrate the proposed three-step procedure on the original and log
      transformed scale of measurement.

PMID- 8981678
TI  - A comparison of different approaches for fitting centile curves to birthweight
      data.
AB  - Centile charts, plotted by week of gestational age, are widely used clinically to
      decide whether a child is 'small-for-dates', indicating that there may have been
      some cause of intra-uterine growth retardation. A variety of different
      statistical techniques have been proposed for constructing centile charts. Some
      methods are distribution free and work on the basis of obtaining and then
      smoothing the empirical centiles. In others the centiles are calculated assuming
      a Normal distribution either of the raw data or of transformed data. In Scotland
      the details of each maternity admission are entered onto an SMR2 form and these
      records are stored centrally by the Scottish Health Service. A data set
      consisting of all live births occurring in Scottish hospitals between 1980 and
      1992 is used to compare different approaches to constructing centile charts.

PMID- 8981679
TI  - Sources of uncertainty in estimating HIV infection rates by back-calculation: an
      application to Italian data.
AB  - The effects on back-calculated HIV diffusion estimates of the uncertainties in a
      number of factors that may potentially influence the estimation process are
      examined and compared. More specifically, the effect on HIV infection estimates
      of uncertainties in: (i) the sequence of periodical AIDS incidence cases; (ii)
      the estimation of the AIDS incubation period, including the influence of
      therapeutic treatment on the same; and (iii) the choice of a particular back
      calculation method, including the stochastic uncertainty associated with each
      method, are examined. The choice of one particular back-calculation model over
      another, among three different methods considered, seems to be a minor component
      of the uncertainty, when compared to the uncertainty, due to all other sources.
      HIV incidence and prevalence in Italy for different risk categories are
      estimated.

PMID- 8981680
TI  - Some statistical issues in project prioritization in the pharmaceutical industry.
AB  - Various aspects of portfolio management and project prioritization within the
      pharmaceutical industry are examined. It is shown that the cost and probability
      architecture of a project is a crucial aspect of its value. An appropriate simple
      tool for ranking projects is the Pearson index. Various difficulties are
      considered.

PMID- 8981681
TI  - Sequential designs for equivalence studies.
AB  - Sequential designs are increasingly being used in major clinical trials
      concerning life-threatening diseases. So far most applications have concerned
      trials designed to establish whether an experimental treatment is superior to a
      control. However, many trials are conducted with the objective of showing that an
      experimental treatment is equivalent to a control. This paper concerns the
      application of sequential designs to equivalence trials. Criteria for claiming
      equivalence are reviewed and compared, and methods first developed in the context
      of bioequivalence are described. Appropriate sequential procedures are
      identified. A simulated example, based on a clinical comparison of
      bronchodilators, is used to illustrate both the double triangular test and a
      comparable procedure constructed from alpha-spending functions.

PMID- 8981682
TI  - Multi-level models for repeated measurement data: application to quality of life
      data in clinical trials.
AB  - Quality of life data present considerable statistical challenges because of their
      longitudinal and multidimensional nature, and also because the available data are
      often very unbalanced through missing values. Here we exemplify the potential of
      multi-level models, that is, hierarchical random coefficient models, for such
      data. The discussion is developed in the context of analysing the quality of life
      data from a trial of palliative treatment in non-small-cell lung cancer. Not only
      do multi-level models provide a flexible modelling framework for the
      investigation of the underlying behaviour of response, for example, giving simple
      estimates of treatment effects, but they also permit a description of the
      differences between subjects and allow the analysis of multi-dimensional
      outcomes. The assumptions of Normality, homogeneity, and independence of the
      within- and between-subject variance components can be investigated and the
      models can be extended to provide explicit modelling of variance heterogeneity.
      It is concluded that multi-level models, for which software is now available,
      provide a natural and powerful approach to the analysis of longitudinal data in
      general, and multi-dimensional quality of life data in particular.

PMID- 8981683
TI  - Borrowing strength from external trials in a meta-analysis.
AB  - There exists a variety of situations in which a random effects meta-analysis
      might be undertaken using a small number of clinical trials. A problem associated
      with small meta-analyses is estimating the heterogeneity between trials. To
      overcome this problem, information from other related studies may be incorporated
      into the meta-analysis. A Bayesian approach to this problem is presented using
      data from previous meta-analyses in the same therapeutic area to formulate a
      prior distribution for the heterogeneity. The treatment difference parameters are
      given non-informative priors. Further, related trials which compare one or other
      of the treatments of interest with a common third treatment are included in the
      model to improve inference on both the heterogeneity and the treatment
      difference. Two approaches to estimating relative efficacy are considered, namely
      a general parametric approach and a method explicit to binary data. The
      methodology is illustrated using data from 26 clinical trials which investigate
      the prevention of cirrhosis using beta-blockers and sclerotherapy. Both sources
      of external information lead to more precise posterior distributions for all
      parameters, in particular that representing heterogeneity.

PMID- 8981684
TI  - An application of a marked point process in pre-clinical medicine.
AB  - Several authors have employed marked point processes to model complex survival
      time data. In this paper it is proposed to illustrate further the flexibility of
      marked point processes by using such a framework to model pre-clinical data which
      comprise survival times accompanied by ordinal outcomes.

PMID- 8981685
TI  - Evaluation of long-term survival: use of diagnostics and robust estimators with
      Cox's proportional hazards model.
AB  - We consider methodological problems in evaluating long-term survival in clinical
      trials. In particular we examine the use of several methods that extend the basic
      Cox regression analysis. In the presence of a long term observation, the
      proportional hazard (PH) assumption may easily be violated and a few long term
      survivors may have a large effect on parameter estimates. We consider both model
      selection and robust estimation in a data set of 474 ovarian cancer patients
      enrolled in a clinical trial and followed for between 7 and 12 years after
      randomization. Two diagnostic plots for assessing goodness-of-fit are introduced.
      One shows the variation in time of parameter estimates and is an alternative to
      PH checking based on time-dependent covariates. The other takes advantage of the
      martingale residual process in time to represent the lack of fit with a metric of
      the type 'observed minus expected' number of events. Robust estimation is carried
      out by maximizing a weighted partial likelihood which downweights the
      contribution to estimation of influential observations. This type of
      complementary analysis of long-term results of clinical studies is useful in
      assessing the soundness of the conclusions on treatment effect. In the example
      analysed here, the difference in survival between treatments was mostly confined
      to those individuals who survived at least two years beyond randomization.

PMID- 8981686
TI  - Comparison of one-sample two-sided sequential t-tests for application in
      epidemiological studies.
AB  - In epidemiological prospective cohort studies, exposure levels of cases with
      disease and disease-free control subjects can be measured by laboratory analysis
      of previously stored biological specimens. In such studies, a sequential t-test
      can be used for preliminary evaluations, at the expense of the smallest possible
      number of specimens, of whether a new aetiological hypothesis is worth further
      investigation or whether specimens should rather be spared to test other, more
      fruitful, hypotheses. For this purpose, we recently compared two sequential
      probability ratio tests (SPRTs), in which the log-likelihood ratio was either
      based on an approximation, or computed exactly, and which were adapted to account
      for various control-to-case matching ratios. The tests turned out relatively
      conservative, particularly in terms of the significance level achieved. In the
      present paper, we compare an SPRT for matched or paired data based on Rushton's
      approximation to the log-likelihood ratio with a profile log-likelihood method
      developed by Whitehead. The comparison is partly mathematical, and partly based
      on computerized simulations. Average sample size for a sequential test is already
      smaller than for the equivalent fixed sample test. Increasing the number of
      controls matched per case further reduces the average sample size necessary to
      come to a decision. We show that, irrespective of the number of controls per
      case, pre-specified levels of statistical power and significance are respected
      closely by Whitehead's method, but not by Rushton's SPRT. This last procedure can
      lead to a significant loss in power. Since, in addition, Whitehead's method has
      been implemented in a commercially available computer program (PEST), we conclude
      that this method can be preferred to the methods we described earlier. Moreover,
      compared with the method of Rushton, Whitehead's method has the advantage that it
      can also be applied to groupwise inspection of the data and that it can also be
      converted easily into a truncated procedure.

PMID- 8981688
TI  - Analysing non-compliance in clinical trials: ethical imperative or mission
      impossible?
AB  - Assuming that a drug is active and different from placebo, a patient's gain or
      loss is likely to depend on how much of the drug is taken and when. The present
      paper motivates the ethical imperative of statistical compliance analysis by
      considering important clinical questions, the advent of more precise compliance
      measuring instruments and new statistical efforts towards well understood
      analyses that seek to preserve scientific integrity. An extension of Efron and
      Feldman's approach is developed which exploits the randomization assumption in
      combination with structural models. It also generates more promising designs and
      alternative statistical approaches.

PMID- 8981687
TI  - On the relationship between response to treatment and survival time.
AB  - In this paper we review several approaches which have been used to investigate
      the relationship between survival time and response to treatment. We show that
      the approaches based on summary data are subjected to various types of biases
      (publication bias, confounding by prognostic features, ecologic bias) and are
      therefore of doubtful value. We also discuss several approaches based on
      individual patient data. Comparisons of survival by response are generally
      subject to length-biased sampling, and are therefore inadequate. The landmark
      method is adequate when responses occur soon after starting treatment, but not
      when responses may appear later in the course of the disease. For responses which
      can occur over extended periods of time, response must be considered as a time
      dependent covariate. Using data from randomized trials in advanced colorectal
      cancer, we show that response is a potent and independent prognostic factor for
      survival in this disease. Analyses using the landmark method yield results
      essentially equivalent to those in which response is considered as a time
      dependent covariate. The hazard rate of responders is about half that of non
      responders, after taking the patient's performance status into account. The issue
      of response as a surrogate marker for survival is taken up further in a separate
      paper.

PMID- 8981689
TI  - Members. American Ophthalmological Society.

PMID- 8981690
TI  - Ophthalmic features of the organoid nevus syndrome.
AB  - BACKGROUND/PURPOSE: The organoid nevus (sebaceous nevus) syndrome is
      characterized primarily by cutaneous sebaceous nevus, seizures, and epibulbar
      choristomas. On the basis of ophthalmoscopic and computed tomographic studies, a
      yellow fundus lesion recently observed in this syndrome has been called a
      coloboma by some investigators and a choroidal osteoma by others. This study was
      undertaken to review our personal experience with the organoid nevus syndrome, to
      review the English language literature on the subject, and to address some
      misconceptions regarding its ocular manifestations. METHODS: We reviewed the
      records of patients with the organoid nevus syndrome who were personally
      evaluated by the investigators. The ocular findings were studied in more detail,
      with emphasis on the epibulbar and fundus lesions. RESULTS: We identified five
      patients with the organoid nevus syndrome. Four had a classic sebaceous nevus in
      the facial and scalp area, and 2 had seizures and arachnoid cysts. All 5 patients
      had an epibulbar tumor, which proved to be a complex choristoma in one case that
      was studied histopathologically. A characteristic ophthalmoscopic feature,
      observed in the 4 patients with clear ocular media, was a flat yellow
      discoloration of the posterior fundus, of variable size and shape, which appeared
      to correlate with a dense plaque noted on ultrasonography and computed
      tomography. In 1 case, histopathologic examination showed that this posterior
      lesion contained intrascleral cartilage. CONCLUSIONS: Our observations and a
      review of the literature indicated that the organoid nevus syndrome has varied
      manifestations. Like the closely related phakomatoses, it often occurs as a forme
      fruste, without full expression of the syndrome. The most important ocular
      manifestations are an epibulbar mass, compatible with a complex choristoma, and
      focal yellow discoloration in the fundus, probably related to intrascleral
      cartilage.

PMID- 8981692
TI  - Ocular and orbital trauma from water balloon slingshots: a clinical,
      epidemiological, experimental, and theoretical study.
AB  - PURPOSE: To report the clinical findings of 17 patients with ocular/orbital
      injuries produced by launched water balloons; to determine water balloon kinetic
      energies in experimental and theoretical studies. METHODS: Six case histories are
      presented, 1 case was retrieved from the medical literature, and 10 cases were
      reported to the National Injury Information Clearinghouse of the United States
      Consumer Product Safety Commission. The energies were determined by field trials
      and calculations. RESULTS: Injuries included orbital contusions and hematomas,
      facial hypesthesia, eyelid lacerations, subconjunctival hemorrhages, corneal
      edema and abrasion, hyphemas, traumatic iritis, iris sphincter ruptures, iris
      atrophy, angle recession, iridodialyses, traumatic cataract, vitreous
      hemorrhages, retinal hemorrhages, macular hole formation, optic atrophy, and bony
      orbital wall fractures. Epidemiological analysis revealed that children and young
      adults, more often males, were injured, most commonly in the warm weather months
      (May through September). In field trials, maximum water balloon velocities ranged
      from 38 to 41 m/sec (85 to 92 mph) with kinetic energies from 176 to 245 J; by
      calculation, maximum velocities ranged from 42 to 54 m/sec (95 to 121 mph) with
      kinetic energies from 141 to 232 J. In a field demonstration a 300-g water
      balloon launched horizontally from a distance of 20 ft exploded a 12-kg
      watermelon. Classic physics calculations are presented to explain the complex bio
      mechanical interactions between the water balloon and the eye. CONCLUSION:
      Kinetic energies of launched water balloons are comparable to or greater than
      kinetic energies experienced with a variety of common objects, including file
      bullets, which are well known to cause serious ocular and orbital injuries. In
      addition, these energies are far in excess of those required to perforate a
      cornea (0.7 to 1.7 J), rupture a globe (1 to 5.3 J), or fracture the bony orbit
      (1.8 to 14.7 j). Thus, this study demonstrates the serious and potentially vision
      and life-threatening injuries inflicted by these "toys."

PMID- 8981693
TI  - The use of computerized videokeratography as an aid in fitting rigid gas
      permeable contact lenses.
AB  - PURPOSE: To assess the efficacy of computerized corneal topography in (1) fitting
      cosmetic rigid gas permeable contact lenses on normal corneas and (2) patients
      who have keratoconus. METHODS: In study 1, 26 patients were fitted with cosmetic
      contact lenses. In 13 patients, the first rigid gas permeable lens was chosen on
      the basis of corneal topography using the EyeSys videokeratoscope and contact
      lens software version 2.11w. Thirteen control patients were fitted with rigid gas
      permeable contact lenses by means of diagnostic contact lenses. The number of
      parameter changes required in each group to reach the best fit were compared. In
      study 2, the records of 28 patients (41 eyes) with keratoconus who had been
      successfully fit with rigid gas permeable lenses were reviewed. Topographic
      analysis using the EyeSys videokeratoscope was conducted. The following 8 data
      points were analyzed: maximum dioptric curvature with respect to the central
      visual axis, the power at the visual axis (VK), the average keratometry readings
      within the 3-mm zone, the average flat K at 3-mm central and 5-mm paracentral
      regions, and the K reading at 1.5, 2.0, and 2.5 mm superior to the visual axis.
      RESULTS: Study 1: In 10 eyes (38%) fitted with cosmetic contact lenses utilizing
      corneal topography and the EyeSys contact lens program, the first lens chosen by
      the computer program was correct with no additional changes in lens parameters
      required. In the other 16 eyes, 21 parameter changes were required. In the
      control group, 14 eyes (53%) required no additional change in parameters from the
      original contact lens that was fitted using diagnostic lenses. In the other 12
      eyes, 12 parameter changes were required. Study 2: In the keratoconus group, of
      the 9 measurements analyzed, the final base curve of patients' rigid gas
      permeable lenses was correlated most closely with the average flat corneal
      curvature at the 3-mm central zone. CONCLUSION: Study 1: In fitting cosmetic
      rigid gas permeable contact lenses, the videokeratoscope with the EyeSys software
      2.11w contact lens program proved to be inferior to diagnostic lenses in
      selecting the final correct contact lens parameters. However, it may be useful in
      selecting an initial diagnostic lens with which to begin rigid gas permeable
      fitting. Study 2: In patients with irregular corneas such as keratoconus, corneal
      topography is helpful in determining the initial base curve of the contact lens.
      In patients with keratoconus, it appears to be the average flat corneal curvature
      at the 3.0-mm zone.

PMID- 8981691
TI  - Ocular hypotensive efficacy and safety of a combined formulation of betaxolol and
      pilocarpine.
AB  - PURPOSE: To evaluate the ocular hypotensive efficacy and safety of a fixed
      combination of betaxolol (0.25%) and pilocarpine (1.75%). METHODS: Three
      multicenter, double-masked, parallel trials were completed in patients with
      primary open-angle glaucoma or ocular hypertension of 3 months' treatment
      duration. Studies 1 and 2 were three-arm comparisons of betaxolol, pilocarpine,
      and a fixed combination, each used 3 times daily. Study 3 was a two-arm study of
      the fixed combination with and without a surfactant, used twice daily. In all
      studies, there was a 1-month runin period with betaxolol 0.25% suspension given
      twice daily. There were 182 patients in Study 1, 186 patients in Study 2, and 166
      patients in Study 3. RESULTS: In all 3 studies, approximately 10% to 15% of
      patients treated with pilocarpine or the combination therapy were terminated from
      further participation because of typical pilocarpine side effects (eg, blurred
      vision, headache). In studies 1 and 2, there was a mean reduction in intraocular
      pressure from a betaxolol baseline of approximately 3 to 4 mmHg. Patients
      continuing on betaxolol alone or randomly assigned to pilocarpine alone
      experienced a mean reduction of 1 to 2 mm Hg. Overall, the combination was
      approximately 2 mmHg more effective than either betaxolol or pilocarpine alone.
      In Study 3, the two betaxolol combinations had equivalent efficacy. CONCLUSION:
      In patients requiring more than one ocular hypotensive agent, the combination of
      betaxolol and pilocarpine in a single formulation appears to be an effective and
      relatively safe agent. The use of this combination agent promises the potential
      for enhanced patient convenience.

PMID- 8981694
TI  - Long-term results of trabeculectomy in eyes that were initially successful.
AB  - A number of published case series provide short-term and intermediate success
      rates for the surgical treatment of glaucoma with trabeculectomy. There is little
      information, however, regarding long-term outcomes that extend beyond 10 years.
      Therefore, we conducted a retrospective study to determine the long-term outcome
      of eyes that had successful trabeculectomy surgery at 1 year (IOP < 21 mmHg, or
      lowering by 33% if preoperative IOP was < 21 mm Hg) and had been followed up for
      at least 10 years. We found 40 such eyes. With respect to IOP control, 83% were
      still considered to be successful at 5 years, 73% at 10 years, but only 42% at 15
      years. Ten percent required additional glaucoma surgery by 5 years, 25% by 10
      years, and 58% by 15 years. Forty percent of the eyes had cataract surgery by the
      time of the last follow-up examination. It appears that there is a significant
      late failure rate of trabeculectomy in eyes that were initially successful.

PMID- 8981695
TI  - Results of levator-advancement blepharoptosis repair using a standard protocol:
      effect of epinephrine-induced eyelid position change.
AB  - PURPOSE: Blepharoptosis repair by levator advancement is successful in most
      instances, but the postoperative eyelid level is not uniformly predictable. This
      study was undertaken to evaluate the possible effect of epinephrine (from local
      anesthetic) on eyelid position. METHODS: Seventeen adults with acquired
      unilateral ptosis as a result of levator aponeurosis dehiscence underwent levator
      aponeurosis advancement. The distance between the upper eyelid margin and the
      central corneal light reflex was measured preoperatively with the patient in both
      the upright and the supine position, 10 minutes after injection of 1.0 mL of
      anesthetic solution (2% lidocaine with 1:100,000 epinephrine and 12 U
      hyaluronidase per mL) in the supine position, intraoperatively after skin closure
      in the supine position, and 1 week or more postoperatively in the upright
      position. The ptotic lid was positioned intraoperatively in relation to the
      contralateral unoperated lid according to the change (presumably) induced by
      epinephrine stimulation of Muller's muscle. RESULTS: Eleven (65%) of the 17
      patients had final postoperative lid positions within 1 mm between eyes. Two
      patients (12%) had undercorrection. Four patients (24%) had overcorrection by > 1
      mm. The overcorrected lids were satisfactorily positioned, however, and none
      required further surgery; in 3 of these 4 patients, the unoperated lid had become
      ptotic, probably as a result of Hering's law. Differences between operated and
      unoperated lids and between the different times of measurement were analyzed.
      Significant changes in lid position occurred in the ptotic lids after injection
      (mean, +1.1 +/- 1.5 mm; median, +1.0 mm; P = .004) and in the final
      intraoperative difference between operated and unoperated lids (mean, +0.8 +/-
      0.9 mm; median, +1.0 mm; P = .003). The change in the unoperated lid from
      preoperative upright to preoperative supine was significantly greater in the 6
      failures (mean, -0.8 +/- 0.6 mm; median, -1.0 mm) than in the 11 successful
      outcomes (mean, +0.1 +/- 0.8 mm; median, 0.0 mm; P = .03). The change in
      unoperated lid position after injection of the ptotic lid was significantly
      greater in the failures (mean, +0.4 +/- 0.5 mm; median, +0.3 mm) than in the
      successful cases (mean, -0.2 +/- 0.4 mm; median, 0.0 mm; P = .02). CONCLUSION:
      Although it seems intuitively reasonable and clinically appropriate to account
      for the stimulatory effect of epinephrine during ptosis surgery, such
      intraoperative compensation alone did not yield a universally successful outcome
      in this study.

PMID- 8981696
TI  - Investigations of antiretinal antibodies in pigmentary retinopathy and other
      retinal degenerations.

PMID- 8981698
TI  - Ipsilateral facial and uveal arteriovenous and capillary angioma, microphthalmos,
      heterochromia of the iris, and hypotony: an oculocutaneous syndrome simulating
      Sturge-Weber syndrome.
AB  - Sturge-Weber syndrome is a disorder characterized by ipsilateral cavernous
      hemangioma of the face, uvea, and brain in patients who may present with an
      enlarged eye, exudative retinal detachment, glaucoma, and seizures. This report
      presents the clinicopathologic findings of an otherwise healthy infant with
      ipsilateral arteriovenous and capillary hemangiomas of the face and uveal tract,
      microphthalmos, iris heterochromia, hypotony, and absence of central nervous
      system involvement. The association of an arteriovenous-capillary angioma of the
      ocular adnexa and ipsilateral uveal tract is a syndrome that is distinct from
      Sturge-Weber syndrome.

PMID- 8981697
TI  - Intermittent diplopia and strabismus caused by ocular neuromyotonia.
AB  - PURPOSE: Two cases illustrate the symptoms, signs, etiologies, and treatment of
      ocular neuromyotonia (ONM). METHODS: The histories, neuroradiologic tests, and/or
      biopsy revealed the etiologies of ONM in both patients. Clinical observations,
      videotaping, and electronic eye movement recordings documented the eye movements.
      RESULTS: A 72-year-old man with chronic arachnoiditis following myelography with
      thorium dioxide (Thorotrast) developed intermittent diplopia and a partial right
      third nerve palsy. Left gaze induced spasm of the right medial rectus. Right gaze
      produced right lateral rectus spasm. A 66-year-old woman, who had radiation
      treatment for a pituitary tumor and acromegaly, had intermittent spasm of the
      left medial rectus muscle and left esotropia. The episodes occurred spontaneously
      and were induced by right gaze. A left internuclear ophthalmoplegia was also
      found. Carbamazepine (Tegretol) abolished the ONM in both patients. CONCLUSIONS:
      Although ONM is an unusual cause of intermittent diplopia and strabismus, its
      distinctive clinical features identify it. Injury to the peripheral cranial
      nerves probably leads to segmental demyelination, axonal hyperexcitability, and a
      self-perpetuating, reverberating circuit, which causes spasms of the extraocular
      muscles.

PMID- 8981700
TI  - Ultrasound biomicroscopy of cystic lesions of the iris and ciliary body.
AB  - OBJECTIVES: To describe and illustrate the ultrasound biomicroscopic findings in
      patients with one or more cystic lesions of the iris, ciliary body, or both.
      METHODS: Retrospective study of 263 ultrasound biomicroscopic studies performed
      at one institution during a 20-month period, May 1994 through December 1995. All
      studies were performed using the Humphrey ultrasound biomicroscope model 840.
      RESULTS: Thirty-nine of the 263 evaluated patients had one or more cystic
      lesions. Four different types of cysts were detected. Twenty-seven patients had
      one or more primary neuroepithelial cysts of the iris or ciliary body. These
      cysts were frequently multifocal and bilateral. All contained clear fluid and had
      a thin but highly reflective wall. Three patients had a stratified squamous
      epithelial implantation cyst. These cysts were all unifocal and unilateral. The
      intracavitary fluid contained multiple suspended particles (presumably
      desquamated epithelial cells), and the walls were relatively thick. Six patients
      had a neuroepithelial cyst associated with a solid tumor. Each of these cysts
      resembled the primary neuroepithelial cysts. Three patients had focal
      intratumoral cavitation. The cavity in each case contained clear fluid. The
      surrounding tumor tissue in each case appeared homogeneous. CONCLUSIONS:
      Ultrasound biomicroscopy appears to be a valuable clinical tool for evaluating
      and differentiating cystic lesions of the iris and ciliary body.

PMID- 8981699
TI  - Intraocular dexamethasone produces a harmful effect on treatment of experimental
      Staphylococcus aureus endophthalmitis.
AB  - BACKGROUND: We created a standardized model of severe Staphylococcus aureus
      endophthalmitis in the aphakic rabbit eye to test various treatment strategies
      involving corticosteroid administration in addition to vitrectomy and antibiotic
      treatment. MATERIALS AND METHODS: In 71 aphakic New Zealand albino rabbit eyes,
      experimental endophthalmitis was created by injecting 10(5) colony-forming units
      of Staphylococcal aureus. The animals were divided into 5 groups. One control
      group was followed up without treatment, while 4 groups were treated with
      vitrectomy and intraocular cefazolin injection. Two groups were also treated with
      intramuscular methylprednisolone, 1 group beginning on the day of surgery and 1
      group beginning on the following day. In the final group, dexamethasone, 400
      micrograms, was injected into the vitreous cavity at the close of surgery.
      Culture results were compared on the first 2 days after surgery. Inflammatory
      scores, including development of total corneal opacity, were assessed over a 21
      day follow-up period, and histopathologic grading was carried out at the
      conclusion of the clinical observations. RESULTS: Simultaneous administration of
      systemic corticosteroids beginning on the day of vitrectomy decreased
      inflammatory scores 1 week after institution of therapy but did not affect final
      scores. Delay of initiation of intramuscular corticosteroid until the first
      postoperative day negated the positive effects. Administration of intraocular
      corticosteroids was associated with an increase in inflammatory scores throughout
      the period of observation, an increase in percentage of eyes that developed
      opaque corneas, an increase in choroidal inflammation graded moderate or severe,
      and an increase in retinal necrosis compared with vitrectomy and cefazolin
      injection alone. CONCLUSIONS: This data suggest caution in the use of intraocular
      corticosteroids in treatment of severe endophthalmitis.

PMID- 8981701
TI  - Sorsby's fundus dystrophy in a family with a Ser-181-CVS mutation in the TIMP-3
      gene: poor outcome after laser photocoagulation.
AB  - PURPOSE: Mutations in the TIMP-3 (tissue inhibitor of metalloproteinase-3) gene
      can cause Sorsby's fundus dystrophy (SFD) and lead to choroidal neovascular
      membrane (CNV) formation. We studied a large American family of Irish Protestant
      descent with CNV inherited as an autosomal dominant trait, to determine the
      phenoptype and to learn whether a mutation was present in TIMP-3. METHODS: Twelve
      members of 5 generations were evaluated clinically, with psychophysical and
      electroretinographic testing, and by fluorescein angiography. Blood samples for
      DNA extraction were obtained from 21 affected and unaffected family members and
      from 1 unrelated spouse. DNA sequence was determined, and affected individuals
      showed a Ser-181-Cys mutation in TIMP-3 exon 5. RESULTS: Observable pathology
      involved primarily the macula, and both the full-field ERG and visual fields were
      normal. Acute CNV occurred during the third through fifth decades, with second
      eyes typically also affected during the subsequent year. Three affected members
      complained of nyctalopia prior to developing CNV. A Ser-181-Cys mutation in the
      TIMP-3 gene cosegregated with CNV in 10 affected subjects but was absent in 3
      relatives at risk and sufficiently old to trust the clinical designation of
      normalcy. Nine eyes of 6 family members were treated by laser photocoagulation by
      5 different ophthalmologists for foveal and juxtafoveal CNV. All eyes had
      recurrent CNV and lost acuity to 20/300 or less within several months.
      CONCLUSIONS: Laser photocoagulation of CNV did not stem vision loss in this SFD
      family. Although possible benefits of laser treatment were not put to formal
      clinical trial owing to the limited number of Sorsby's cases, it appears that
      photocoagulation is not of long-term benefit for preserving vision loss from the
      TIMP-3 Ser-181-Cys mutation. Several younger family members with the mutation are
      thus far not clinically affected and are being followed up.

PMID- 8981702
TI  - Multiple changes in oncogenes and tumor suppressor genes in human retinoblastoma.
AB  - PURPOSE: To present data to support the hypothesis that human retinoblastoma
      tumors form by a multistep process. METHODS: Survey of the karyotype of 90 human
      retinoblastomas, with emphasis on changes in chromosomal regions known to contain
      oncogenes and tumor suppressor genes. CONCLUSION: The data support the hypothesis
      that retinoblastoma occurs after multiple and often varied steps, similar to
      other human malignancies.

PMID- 8981703
TI  - Surgical treatment of superior oblique palsy.
AB  - Reports of several large series of patients with superior oblique palsy (SOP)
      published in 1986 or before set forth important guidelines for both diagnosis and
      treatment of this condition. Newer information about the anatomy, physiology, and
      pathophysiology of the superior oblique has accrued over the past decade. This
      paper reviews our experience with diagnosis and treatment of SOP over the past 5
      years in light of this new information. Charts of patients treated for SOP over 5
      year (1990 to 1995) were reviewed for male or female sex, age, symptoms,
      refraction, vision, stereo acuity, head posture, facial asymmetry, intraoperative
      superior oblique traction test, diagnostic position prism and cover test,
      torsion, surgery performed, and results of treatment. The charts of 190 patients
      were reviewed. In 181, postoperative examinations were performed by us. The
      etiology of the SOP was congenital in 137 and acquired in 53. Twenty-nine
      acquired cases were due to trauma and 24 arose from other causes. Fifty-six
      patients had facial asymmetry, 51 of whom had congenital SOP. Ninety-five had a
      lax tendon, 83 (87%) of whom had congenital SOP. Sixty-six had a normal tendon,
      29 (44%) of whom had acquired SOP. Seventy-seven percent of patients had Knapp
      class I, III, or IV palsy. An average of 1.26 surgeries was performed per
      patient. Inferior oblique weakening was performed in 177 (93%), while 68 vertical
      rectus recessions were done. Thirty-five patients had superior oblique tuck or
      resection, all on lax tendons, and 15 had Harada Ito procedures for torsion. Six
      patients had mild Brown syndrome postoperatively, none of which required a
      takedown. A cure, defined as relief of symptoms or elimination of strabismus and
      head tilt, was achieved in 166 of 181 (92%) of patients. Successful treatment of
      SOP can be accomplished in the majority of cases by selective surgery usually
      beginning with inferior oblique weakening plus additional vertical rectus and
      horizontal surgery as needed, with superior oblique strengthening used only for
      lax tendons or when torsion is the main problem.

PMID- 8981705
TI  - Results following secondary intraocular lens implantation in children.
AB  - BACKGROUND: Placement of a secondary intraocular lens (IOL) in a child may be
      considered in children with congenital monocular cataracts who have had complete
      opacities removed early in life and who later become contact lens intolerant, in
      eyes that have received trauma which precluded placement of a primary IOL, and in
      young adults who have bilateral aphakia who become resistant to use of contact
      lenses or spectacles. METHODS: Clinical records of all children in our practice
      who received a secondary IOL between January 1988 and December 1994 were
      reviewed. Indications, biometry, type of procedures, preoperative and
      postoperative acuity, refractive error, binocular status, and complications were
      studied. RESULTS: During the 7-year period, 242 cataract operations were
      performed. Fifty-nine eyes received a lens implant, and 28 of these were
      secondary implants. There was a mean interval between the initial cataract
      operation and the procedure for the secondary implant of 77 months. The mean
      follow-up was 35 months (range, 3 to 71) for the 28 eyes that received a
      secondary implant. Two received anterior chamber implants. Eight eyes had
      insufficient capsular support for an IOL. Six implants were placed in the
      posterior chamber and required suture fixation to the sclera. Twenty of 28 eyes
      had a measurable improvement in visual acuity. Only 1 eye had a decrease in
      visual acuity of 2 lines. Fifteen patients (54%) had a final refraction within
      1.50 diopters of the fellow eye, and 75% were within 3.00 diopters. During the
      follow-up period, 2 eyes developed glaucoma. One had a transient pressure
      elevation, and the second has required 2 filtration procedures. Three patients
      required a Nd: YAG capsulotomy. Six patients demonstrated Worth fusion at
      distance and near, but only 3 patients demonstrated 200 seconds of arc or better
      stereo acuity. CONCLUSION: Placement of contemporary-style, secondary intraocular
      lenses in children and young adults appears to provide a safe and effective
      alternative for correction of aphakia in children who become contact lens or
      spectacle-intolerant.

PMID- 8981704
TI  - Juvenile glaucoma linked to GLCIA in a Panamanian family.
AB  - PURPOSE: To carry out clinical and genetic characterization of juvenile-onset
      primary open-angle glaucoma (POAG) inherited as an autosomal dominant trait in a
      Panamanian family. METHODS: Twenty-two members of a six-generation Panamanian
      family underwent an ophthalmologic evaluation. Blood samples were collected from
      20 of these individuals for preparation of DNA for use in screening of
      microsatellite repeat genetic markers via polymerase chain reaction. RESULTS:
      Eleven living family members covering 4 generations were diagnosed as affected
      with open-angle glaucoma of primarily juvenile onset. Four of 6 other at-risk
      individuals examined and enrolled were characterized as unaffected and two as
      indeterminate. Two additional individuals were not included in this study because
      they were too young to characterize or to provide a blood sample. Three spouses
      of affected family members were also examined and found not to have glaucoma. Of
      clinical importance was the finding of markedly elevated intraocular pressure
      (IOP) in 2 affected brothers, both of whom were advised to have urgent filtration
      surgery; the finding of elevated IOP in the only seeing eye of the mother of
      these brothers, causing us to advise her to pursue more aggressive treatment; and
      the finding of early signs of glaucoma in a previously undiagnosed 9-year-old
      family member. Linkage analysis using selected microsatellite repeat markers in
      the 1q21-q31 region revealed strong evidence for linkage to the GLC1A gene with a
      maximum lod score of 3.75 for marker D1S431 at a recombination fraction of 0.00.
      CONCLUSIONS: The most likely interpretation of our data is that a mutation in the
      GLC1A gene is responsible for juvenile-onset POAG in this Panamanian family, thus
      expanding the countries of origin where this gene has been found to exist. The
      numbers of families with GLC1A glaucoma now reported from only a few centers
      worldwide raise questions about whether this disease may be more common than once
      thought. Evaluation of treatment histories and clinical outcomes in members of
      this and other previously reported families indicates that ophthalmologists need
      to understand the necessity for urgent filtration surgery in most cases of GLC1A
      glaucoma if vision is to be preserved.

PMID- 8981707
TI  - Apoptosis in human retinal degenerations.
AB  - PURPOSE: This paper examined the role of apoptosis in human retinal degenerations
      including pathologic myopia, age-related macular degeneration, serous retinal
      detachment, retinal lattice, and paving stone degenerations. METHOD: Thirty-seven
      enucleated human eyes with 1 of the above-mentioned retinal degenerations were
      studied by histopathology and by TdT-mediated biotin-dUTP nicked-end labelling
      (TUNEL) technique. RESULTS: Tunnel labelling characteristic DNA fragmentation of
      apoptosis was observed in photoreceptor cells in 2 of the 4 eyes with pathologic
      myopia and in 4 of 16 eyes with age-related macular degeneration, 2 of which were
      exudative and 2 of which were atrophic. However, only a few scattered
      photoreceptor cells were labelled in 4 of 8 eyes with serous retinal detachment
      secondary to malignant melanoma of the choroid. Moreover, none of the
      photoreceptors cells in the 4 eyes with retinal lattice degeneration and 6 eyes
      with retinal paving stone degeneration were labelled. CONCLUSIONS: Apoptosis is 1
      of the important pathways of photoreceptor cell degeneration in pathologic myopia
      and age-related macular degeneration.

PMID- 8981706
TI  - A unification hypothesis of pigment dispersion syndrome.
AB  - PURPOSE: To synthesize recent findings regarding pigment dispersion syndrome in
      order to arrive at a hypothesis concerning the nature of an underlying genetic
      predisposition. METHODS: The literature on the subject was reviewed and analyzed.
      RESULTS: Eyes with pigment dispersion syndrome differ from normal in that they
      have a larger iris, a midperipheral posterior iris concavity that increases with
      accommodation, a more posterior iris insertion, increased iridolenticular contact
      that is reversed by inhibition of blinking, possibly an inherent weakness of the
      iris pigment epithelium, and an increased incidence of lattice degeneration of
      the retina. CONCLUSION: A gene affecting some aspect of the development of the
      middle third of the eye early in the third trimester appears at the present time
      to be the most likely cause.

PMID- 8981708
TI  - The Vanderbilt Classification System in the evaluation of diabetic retinopathy
      patients treated with Alredase.
AB  - BACKGROUND: The Vanderbilt Classification System is a quantitative method of
      measuring features detected in diabetic retinopathy photographs. It does not
      require comparisons to preexisting standard photographs. This is the first report
      of the application of this system to a large-scale, multiple-medical-center drug
      trial. METHODS: This was a prospective, randomized, double-masked, placebo
      controlled study that involved 74 medical centers. There were 3,679 out-patients
      followed for more that 4 years, with some observed for over 9 years. The
      Vanderbilt Classification System generated patient data for the Early Treatment
      Diabetic Retinopathy Study (ETDRS) and the Diabetes Control and Complication
      Trial (DCCT) scales. The deterioration rate was one variable used to assess drug
      effect. A comprehensive Quality Assurance Program evaluated intergrader and
      intragrader reliability. RESULTS: Target values for reliability and
      reproducibility were met or exceeded on all measures of agreement between photo
      readers and over time. Kappa statistics were 0.610 or greater, with most weighted
      kappa values greater than 0.810. This represents "almost perfect agreement" and
      compares favorably with previous reports from the ETDRS and DCCT. CONCLUSION:
      Diabetic retinopathy can be evaluated in a reliable and reproducible manner with
      the VCS. The VCS is unique in that it produces a quantitative analysis of retinal
      lesions. Subtle variations that might be influenced by systemic medications can
      be measured accurately with this technique.

PMID- 8981709
TI  - Temporal corneal phacoemulsification combined with superior trabeculectomy: a
      controlled study.
AB  - OBJECTIVE: To determine the intraocular pressure (IOP)-lowering effects of
      combined temporal corneal phacoemulsification and separate incision superior
      trabeculectomy with those of trabeculectomy alone. METHODS: This is a
      retrospective case-control study of 40 consecutive patients who underwent
      combined temporal corneal phacoemulsification and superior trabeculectomy with
      low-dose 5-fluorouracil (5-FU) (cases), and 40 eyes matched with respect to age,
      race, preoperative medications, and preoperative IOP that had trabeculectomy
      alone with low dose 5-FU (controls). Survival analyses for IOP were performed for
      the cases and controls. We reviewed the charts of 40 consecutive patients who
      underwent combined temporal corneal phacoemulsification and superior
      trabeculectomy with low dose 5-FU to determine the effect on IOP, visual acuity,
      and requirement for glaucoma medications. For controls, we chose 40 eyes matched
      with respect to age, race, preoperative medications, and preoperative IOP who had
      trabeculectomy alone with low dose 5-FU. In both groups, trabeculectomy was
      performed with the same technique, was located superiorly, and employed a limbus
      based conjunctival flap. In the combined surgery group, temporal corneal
      phacoemulsification immediately preceded trabeculectomy and employed a 3.5-mm
      incision and a one-piece silicone intraocular lens. All patients received 3 or 4
      subconjunctival 5-FU injections of 5 mg each over the first 11 postoperative
      days. Patients were followed up for at least 1 year. Success of trabeculectomy
      was defined as an IOP less than 22 mmHg and 20% or more reduction from the
      preoperative level on 2 consecutive follow-up visits, regardless of the use of
      antiglaucoma medications. RESULTS: The mean postoperative intraocular pressure
      was higher in the combined surgery group than in the control group at each follow
      up interval (P < 0.05). The mean (+/- SD) IOP reduction was 6.8 (+/- 5.5) mmHg in
      the combined surgery group, and 10.3 (+/- 7.6) mmHg in the trabeculectomy group
      at 1 year. The reduction in the number of antiglaucoma medications was 1.6 (+/-
      0.9) in the combined surgery group and 2.0 (+/- 1.0) in the control group at 1
      year. In the combined surgery group, the mean visual acuity beyond the first
      postoperative month was significantly better than at baseline (P < 0.001). Kaplan
      Meier survival analysis showed that the cumulative success rate at 2 years was
      62% in the combined surgery group and 86% in the trabeculectomy group. The time
      to failure was significantly shorter (P = 0.04) in the combined surgery group.
      CONCLUSIONS: Combined surgery for cataract and glaucoma is associated with less
      long-term IOP reduction compared with trabeculectomy alone, despite identical
      trabeculectomy techniques in both groups. Nevertheless, combined surgery
      effectively lowers IOP and reduces the long-term requirement for antiglaucoma
      medications without additional complications. This technique is appropriate in
      selected patients with coexisting cataract and glaucoma.

PMID- 8981710
TI  - Thrombolytic therapy for central retinal vein occlusion: results of a pilot
      study.
AB  - OBJECTIVE: To evaluate the feasibility of conducting a randomized, controlled
      trial of thrombolytic therapy for central retinal vein occlusion (CRVO) using
      tissue plasminogen activator (TPA); to establish relative efficacy and safety of
      various dosing regimens. DESIGN AND PATIENTS: Ninety-six patients with CRVO were
      treated with TPA between May 1986 and December 1992. Prior to patient enrollment,
      a standardized, detailed protocol was developed for evaluation and treatment of
      all patients. This included standard protocols for determining eligibility,
      reporting complications, performing photography and electroretinography, and
      measuring visual acuity. MAIN OUTCOME MEASURES: Best corrected visual acuity at 6
      months, systemic and ophthalmic treatment complications. RESULTS: At 6 months'
      follow-up, 42% (n = 89) of eyes gained three or more lines of vision from
      pretreatment levels (average gain, 5.1 lines), 37% remained stable, and 21% lost
      three or more lines. Of eyes with 20/100 or worse pretreatment vision (n = 32),
      59% gained three or more lines vision (average gain, 6.4 lines), 31% remained
      stable, and 9% lost three or more lines. One patient suffered a fatal stroke.
      Three patients developed intraocular bleeding during TPA administration.
      CONCLUSION: Thromobolytic therapy with TPA appears to be a promising, albeit
      risky, new treatment; conclusive evaluation of safety and efficacy awaits a
      multicenter, randomized, clinical trial; feasibility of such a trial has been
      established by this study.

PMID- 8981711
TI  - Early photocoagulation in patients with either type I or type II diabetes.
AB  - OBJECTIVE: To determine the benefits of early photocoagulation in patients with
      type I versus type II diabetes. DESIGN: One eye of each of 3,711 patients was
      randomly assigned to early photocoagulation; the other was assigned to deferral
      of photocoagulation, with follow-up visits scheduled every 4 months and
      photocoagulation to be carried out promptly if high-risk proliferative
      retinopathy developed. Patients were categorized by age and type of diabetes.
      MAIN OUTCOME MEASURES: Best corrected visual acuity was measured at each study
      visit scheduled at 4-month intervals. Stereoscopic fundus photographs were taken
      and evaluated at baseline, 4 months, and yearly thereafter. Retinopathy severity
      was assessed from fundus photographs. Severe visual loss was defined as visual
      acuity of worse than 5/200 for at least two consecutive study visits. RESULTS:
      Previously published results of the Early Treatment Diabetic Retinopathy Study
      (ETDRS) demonstrated a statistically significant benefit of early
      photocoagulation in preventing severe vision loss. Further analyses demonstrate
      that this benefit of early photocoagulation is greater in patients with type II
      diabetes than in those with type I. The relative benefit of early
      photocoagulation in patients with type II diabetes is also seen for other
      outcomes (development of high-risk proliferative retinopathy, development of the
      combined end point [severe visual loss or vitrectomy], development of moderate
      visual loss, or development of legal blindness). The patients most likely to
      benefit from early photocoagulation had severe nonproliferative retinopathy or
      early proliferative retinopathy. Analyses from the Diabetic Retinopathy Study
      confirm the relative benefit of scatter photocoagulation for type II patients.
      Because of the high correlation between age and type of diabetes, analyses sub
      grouped by age show similar results. CONCLUSION: These analyses suggest that
      patients with type II diabetes, or older patients with diabetes, are more likely
      to benefit from early scatter photocoagulation than patients with type I
      diabetes. The current standard of care is to initiate scatter photocoagulation as
      the severity of retinopathy approaches or reaches the high-risk stage, Provided
      careful follow-up is possible, ETDRS data do not show that initiating scatter
      photocoagulation prior to the development of high-risk proliferative diabetic
      retinopathy in patients with type I diabetes will reduce the risk of severe
      visual loss. ETDRS analyses do indicate that for patients with type II diabetes,
      it is especially important to consider scatter photocoagulation at the time of
      the development of severe nonproliferative or early proliferative retinopathy.

PMID- 8981712
TI  - Surveillance and control of epidemic keratoconjunctivitis.
AB  - PURPOSE: The purpose of this study was to determine if the implementation of a
      formal set of infection-control policy and procedures (ICPPs) can reduce the
      number of outbreaks of epidemic keratoconjunctivitis (EKC) and the number of
      nosocomially infected patients in a large teaching eye institute. METHODS: A
      retrospective and prospective study of the incidence of EKC and the number of
      affected patients was performed for the years 1984 through 1991. Infection
      control measures (ICPPs) were formulated in 1992 with regulations implemented for
      patient control and management, hand washing, instrument disinfection, medication
      distribution, and employee furloughs. Two levels of ICPPs were established on the
      basis of nonepidemic or epidemic conditions. After implementation of ICPPs, a
      prospective 4-year study (1992 through 1995) and statistical analysis were
      performed to determine whether the number of outbreaks of EKC and affected
      patients significantly decreased. RESULTS: The incidence of institutional EKC
      epidemics per year was at least one and as many as three from 1984 through 1991.
      After implementation of a formal set of ICPPs, no epidemics occurred in 2 of 4
      years studied. The number of epidemics and affected patients was significantly
      less when the years before and after implementation of ICPPs were compared by chi
      square analysis (P < .01 and P <. 01, respectively). CONCLUSIONS: In this first
      prospective study of institutional outbreaks of EKC, the implementation of ICPPs
      was demonstrated to be an effective means to decrease the number of EKC outbreaks
      and nosocomially infected patients for this particular institution. Although
      several reports of institutional outbreaks of EKC have described infection
      control measures that eventually controlled an outbreak well under way, this
      study provides policies and procedures that may effectively decrease the number
      and size of nosocomial epidemics of adenoviral conjunctivitis in large teaching
      eye institutions.

PMID- 8981714
TI  - Epithelial transplantation for the management of severe ocular surface disease.
AB  - PURPOSE: First, to present a new classification of epithelial transplantation
      procedures for ocular surface disease; second, to present our experience with a
      keratolimbal allograft procedure for limbal stem cell deficiency; and third, to
      make recommendations for the indications and postoperative management of
      epithelial transplantation procedures. METHODS: A review of all epithelial
      transplantation procedures was performed. A classification of these procedures
      based on the source of donor tissue and the tissue transplanted was proposed. In
      addition, a review of 25 eyes of 21 patients who underwent a keratolimbal
      allograft was completed. Ocular surface stability, improvement of visual acuity,
      success of subsequent keratoplasties, and preoperative risk factors were
      evaluated. Results were compared with those of other epithelial transplantation
      procedures for ocular surface disease. On the basis of the results of published
      studies, as well as ours, a recommendation for the indication of the various
      procedures was made. RESULTS: Epithelial transplantation for ocular surface
      disease can be classified as one of the following procedures: conjunctival
      autograft (CAU), conjunctival allograft (CAL), conjunctival limbal autograft
      (CLAU), cadaveric conjunctival limbal allograft (c-CLAL), living related
      conjunctival limbal allograft (lr-CLAL), or keratolimbal allograft (KLAL).
      Evaluation of our keratolimbal allograft patients revealed that 18 of 25 eyes
      (72%) developed a stable ocular surface. Fifteen eyes (60%) demonstrated a
      significant improvement in visual acuity. Persistent epithelial defects and
      symblephara were successfully managed with this procedure. Six of 13 (46%)
      subsequent keratoplasties were successful. Patients with limbal deficiency due to
      Stevens-Johnson syndrome had a significantly worse outcome. Patients with
      preoperative conjunctival keratinization also had a significantly worse outcome.
      Indications for epithelial transplantation are as follows: For patients with
      unilateral cicatrizing conjunctival disease, the first option should be CAU. For
      patients with unilateral limbal deficiency, CLAU is the procedure of choice. For
      patients with bilateral disease Ir-CLAL should be considered first. If this
      procedure is not available, then consideration of KLAL is warranted. CONCLUSIONS:
      Classification of the various epithelial transplantation procedures based on
      anatomy is useful for an accurate comparison and discussion of the procedures.
      KLAL is a useful technique in the management of severe ocular surface disease due
      to limbal deficiency. However, patients with preoperative conjunctival
      keratinization have a poor prognosis. Consideration of a CLAU or a Ir-CLAL should
      be made for ocular surface disease on the basis of whether the disease is
      unilateral or bilateral. The importance of HLA and ABO typing, as well as the
      protocol for immunosuppression in the allograft procedures for limbal deficiency,
      needs further study.

PMID- 8981713
TI  - Transvitreal endocyclophotocoagulation.
AB  - PURPOSE: Transvitreal endophotocoagulation of the ciliary processes is a little
      used option for eyes with refractory glaucoma. No histopathologic studies of
      animals or humans have described its effects. We sought to characterize this
      cilioablative procedure in an animal model, examine its effects in human eyes
      histopathologically, and evaluate its clinical safety and efficacy in a large
      series of patients with long-term follow-up. METHODS: ANIMAL MODEL: Rabbit eyes
      were treated with lensectomy, vitrectomy, and transvitreal photocoagulation of
      the ciliary processes. Eyes were enucleated immediately after surgery and at
      weekly intervals up to 1 month. Light and electron microscopic evaluation of
      histopathologic changes was performed. Human Eyes: The pathology laboratory files
      were searched for cases with a history of endocyclophotocoagulation prior to
      enucleation, and three eyes were identified. Histopathologic sections were
      retrieved and examined. Clinical Series: A retrospective clinical review was
      performed of a single surgeon's experience with endolaser to the ciliary
      processes, including all cases with adequate data on ocular history, preoperative
      and postoperative visual acuity, intraocular pressure (IOP), and glaucoma
      medications, and details of surgery. Only eyes with at least 6 months' follow-up
      were included. RESULTS: ANIMAL MODEL: Histopathologic examination of rabbit eyes
      treated with endocyclophotocoagulation demonstrated acute changes of ciliary
      process destruction, proteinaceous exudate, stromal edema, nuclear pyknosis, and
      pigment dispersion. Vascular congestion was seen with some hemorrhage. Later,
      replacement by fibrous or fibrovascular scar developed with loss of the pigmented
      and nonpigmented ciliary epithelia, absence of ciliary architectural elements,
      and pigment rounding and clumping. Human Eyes: Histopathologic examination of
      enucleated human eyes revealed total ablation of the ciliary processes with
      fibrosis and pigment clumping in areas of treatment. Abrupt transitions between
      treated and untreated regions could be identified. In some areas fibrocellular
      membrane proliferation was found extending over the scars that replaced the
      ciliary processes. Clinical series: Seventy-three patients were identified
      ranging in age from 2 to 85 years (mean, 57.7), with follow-up of 6 to 130 months
      (mean, 28.6). Mean number of previous operations was 3.5; mean number of previous
      glaucoma operations was 1.3. Preoperative mean IOP was 38 mmHg (range, 19 to 75),
      postoperative mean IOP was 16 mmHg (range, 1 to 50). At 6 months, 58 of 72 eyes
      (81%) with available IOP data had IOP greater than 5 mmHg and less than 22. At 12
      months 48 of 55 (87.3%) were successfully controlled by these criteria, and at
      last follow-up 50 of 73 (68%). Fifty-six of 73 eyes (77%) were considered
      clinically stable at the last follow-up in terms of visual acuity, anatomic
      integrity, and IOP < or = 23 off all glaucoma medications. Visual acuity was
      stable or improved in 53 of 73 eyes (73%). Complications developed in 9 eyes
      (12%), including IOP < or = 6 mmHg in 6 eyes (8.2%), peripheral choroidal
      effusion in 4 (5.5%), fibrinous anterior chamber reaction in 3 (4.1%), phthisis
      in 2 (2.7%), and choroidal hemorrhage in 1. Thirty-five eyes had penetrating
      keratoplasty performed before or at the same time as endolaser (an average of
      2.14 grafts each), Graft rejection occurred in 4 eyes (11%), and long-term
      failure of grafts occurred in 11 of 35 (31%). In 31 eyes, additional surgical
      procedures were performed at the time of endocyclophotocoagulation. CONCLUSIONS:
      Endocyclophotocoagulation successfully ablates the ciliary processes, which are
      replaced with fibrous scar. Surgical results compare favorably with other methods
      of glaucoma therapy in complicated eyes in terms of IOP control, visual
      preservation, and complication rate. Endolaser to the ciliary body was especially
      successful in glaucomatous eyes after keratoplasty, although corneal graft
      prognosis

PMID- 8981715
TI  - Histological changes and wound healing response following noncontact holmium: YAG
      laser thermal keratoplasty.
AB  - PURPOSE: To evaluate acute histological changes and the induced wound healing
      response in corneal tissue following noncontact holmium:YAG laser thermal
      keratoplasty (LTK). METHODS: LTK using 10 pulses and a range of radiant energies
      was performed on 3 human corneas one day prior ro their removal at penetrating
      keratoplasty. Rabbit corneas were treated with 10-pulse and 5-pulse LTK and
      followed for up to 3 months. Tissues were studies with light and transmission
      electron microscopy and immunohistochemistry. RESULTS: The amount of acute tissue
      injury increased with increasing pulse radiant energy. In human corneas, changes
      in the irradiated zones included epithelial cell injury and death loss of fine
      filamentous structure in Bowman's layer, disruption of stromal lamallae, and
      keratocyte injury and death. In the rabbit corneas, similar acute changes were
      noted. By 3 weeks, epithelial hyperplasia and stromal contraction were present.
      Wound healing in the rabbit corneas included repair of the epithelial attachment
      complex, keratocyte activation, synthesis of type I collagen, partial restoration
      of stromal keratan sulfate and type VI collagen, and retrocorneal membrane
      formation. Compared to 10-pulse treatments, 5-pulse treatments produced less
      acute tissue injury and had more rapid restoration of normal stromal
      architecture. CONCLUSION: Noncontact LTK produces acute epithelial and stromal
      tissue changes and in rabbit corneas stimulates a brisk wound healing response.
      These changes could contribute to postoperative regression of induced refractive
      correction. Further work is required to determine if reductions in the magnitude
      of acute tissue injury and induced wound healing response will enhance the
      efficacy and stability of LTK.

PMID- 8981716
TI  - The concentration of light in the human lens.
AB  - PURPOSE: This thesis explores the idea that light energy, especially ultraviolet
      light, contributes to the unequal distribution of cataract around the world and
      to the development of cortical opacities. METHODS: In the first section, the
      thesis reviews historical concepts of the function of the lens and the nature of
      cataract, epidemiologic data on the global distribution of cataract, and clinical
      observations of the predominant location of cortical opacification. Second,
      computer ray tracings and geometric optics demonstrate the passage of light of
      varying angle of incidence within the lens. Third, two models of the human eye
      are used to study the refraction of light by the cornea and lens and illustrate
      the concentration of energy at the equatorial plane of the lens. RESULTS:
      Cataract prevalence increases with proximity to the earth's equator, and cortical
      cataract is most common in the inferior and inferonasal lens. Theoretical studies
      and the eye models both demonstrate that the concentration of light within the
      lens increases with angle of incidence, and the eye models suggest that the
      inferior and inferonasal lens receives significantly more energy than other
      sections of the lens. CONCLUSION: The prevalence of cataract and exposure to
      ultraviolet energy both increase with decreasing latitude. The most common
      location of cortical cataract in the inferonasal lens is consistent with the
      greater dose of light energy received by this portion of the lens. These studies
      suggest that the global distribution of cataract and the development of cortical
      cataract are at least in part dependent on the dose of ultraviolet light received
      by the lens.

PMID- 8981717
TI  - Visual impairment, visual functioning, and quality of life assessments in
      patients with glaucoma.
AB  - BACKGROUND/PURPOSE: To determine the relation between visual impairment, visual
      functioning, and the global quality of life in patients with glaucoma. METHODS:
      Visual impairment, defined with the American Medical Association Guides to the
      Evaluation of Permanent Impairment; visual functioning, measured with the VF-14
      and the Field Test Version of the National Eye Institute-Visual Functioning
      Questionnaire (NEI-VFQ); and the global quality of life, assessed with the
      Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), were determined
      in 147 consecutive patients with glaucoma. RESULTS: None of the SF-36 domains
      demonstrated more than a weak correlation with visual impairment. The VF-14
      scores were moderately correlated with visual impairment. Of the twelve NEI-VFQ
      scales, distance activities and vision specific dependency were moderately
      correlated with visual impairment. Of the twelve NEI-VFQ scales, distance
      activities and vision specific dependency were moderately correlated with visual
      field impairment; vision specific social functioning, near activities, vision
      specific role difficulties, general vision, vision specific mental health, color
      vision, and driving were modestly correlated; visual pain was weakly correlated;
      and two were not significantly correlated. Correcting for visual actuity weakened
      the strength of the correlation coefficients. CONCLUSIONS: The SF-36 is unlikely
      to be useful in determining visual impairment in patients with glaucoma. Based on
      the moderate correlation between visual field impairment and the VF-14 score,
      this questionnaire may be generalizable to patients with glaucoma. Several of the
      NEI-VFQ scales correlate with visual field impairment scores in patients with a
      wide range of glaucomatous damage.

PMID- 8981719
TI  - The neurofibrovascular bundle of the inferior oblique muscle as its ancillary
      origin.
AB  - PURPOSE: To establish that the neurofibrovascular bundle (NFVB) of the inferior
      oblique muscle (IO) has ligamentous qualities that enable it to function as an
      ancillary origin to the muscle. Also, to show that the NFVB does function as the
      ancillary origin for the IO muscle, particularly when recessing and anteriorly
      transposing its insertion. METHODS: Fresh (no formaldehyde preservative) cadaver
      and patient eyes were studied anatomically, histologically, and physiologically.
      Eighteen orbits were dissected to isolate the IO, the inferior rectus (IR), and
      the NFVB to demonstrate the linear course of the NFVB and its adjacent fibrous
      bands. The shape of the muscle was documented. Coronal sections of the two whole,
      intact orbits were analyzed histologically. Light and electron microscopic
      sections of an autopsy specimen and a surgical specimen were used to evaluate the
      capsule of the NFVB and the adjacent fibrous bands near the anterior portion of
      the NFVB and their attachment to the IR and IO muscle capsules. The elastic
      modulus was measured in six in situ and six in vitro cadaver NFVB specimens and
      in six in vivo surgical cases at the time of denervation of the NFVB. For
      additional comparison, four in vitro cadaver superior oblique tendons were
      similarly tested. Six eyes that developed recurrent IO overaction following an
      anterior transposition procedure were surgically explored to determine what
      structure was serving as its ancillary origin. RESULTS: Gross anatomic and
      microscopic studies showed a linear orientation of the NFVB with adjacent fibrous
      bands anteriorly joining the IO and IR muscle capsules. The surgical specimens of
      the anterior portion of the NFVB show about 50% nerve and 50% fibrocollagenous
      capsule with the collagen fibers aligned parallel to the NFVB. The elastic
      modulus was highest (stiffest) in surgical specimens of the NFVB and in situ
      cadaver NFVB, followed by in vitro cadaver NFVB and, finally, in vitro cadaver
      superior oblique tendon. In patients who have undergone anterior transposition
      surgery, the NFVB served as the ancillary origin of the IO. CONCLUSIONS: The name
      of the neurovascular bundle should be changed to the NFVB, since it has a
      prominent fibrocollagenous capsule and it is encased in fibrous tissue bands
      anteriorly. The NFVB has a linear course in the orbit from the apex to the IO
      muscle and is relatively stiff. The associated fibrous band extends posteriorly
      from the IO muscle capsule, encasing the nerve anteriorly and attaching 3 to 7 mm
      posteriorly into the capsule of the IR. The NFVB binds the mid posterior portion
      of the IO posteriorly. Its ligamentous qualities enable the NFVB to function as
      an ancillary origin for the IO.

PMID- 8981718
TI  - Experimental nonenzymatic glycosylation of vitreous collagens occurs by two
      pathways.
AB  - PURPOSE: To study the process of nonenzymatic glycosolation of vitreous collagen
      in vitro to determine the contributions of the classic Maillard pathway and the
      oxidative pathway, as well as to evaluate possible inhibitors of both pathways.
      METHODS: Bovine vitreous collagen was extracted and then incubated with hexoses
      in vitro. The amount of advanced glycosylation end (AGE) products was measured by
      fluorometry under varying conditions in the presence and absence of glycosolation
      inhibitors. Oxygen consumption studies and electron spin resonance spectroscopy
      with and without free-radical inhibitors were performed to differentiate
      oxidative from nonoxidative glycosolation. RESULTS: Vitreous collagen undergoes
      nonenzymatic glycosolation in the presence of glucose or galactose in vitro.
      Oxygen consumption data show that oxygen is consumed in glucose and galactose
      solutions. Oxygen consumption is decreased by known free-radical inhibitors and
      rutin but not aminoguanidine. Electron spin resonance spectroscopy demonstrated
      the presence of a carbon-centered radical, and known free-radical inhibitors
      decreased the carbon-centered signal. CONCLUSIONS: Nonenzymatic glycosolation of
      vitreous collagen can occur not only by the classic nonoxidative pathway, but
      also by a second oxidative pathway that is susceptible to a number of inhibitors.

PMID- 8981721
TI  - The efficacy of a single continuous nylon suture for control of post keratoplasty
      astigmatism.
AB  - PURPOSE: Post operative adjustment of a single continuous suture is an effective
      means of reducing post keratoplasty astigmatism. This study evaluates post
      keratoplasty keratometry following suture adjustment with an adjusted suture in
      place and after the suture is removed. METHODS: Average keratometric astigmatism
      was measured over 24 months time in 26 patients with an adjusted continuous
      suture and 24 patients with a continuous suture that was not adjusted. Average
      keratometry in 43 patients with an adjusted continuous suture was compared with
      37 patients with combined continuous and interrupted sutures. Finally, suture out
      astigmatism in 19 adjusted patients was compared to six patients with no
      adjustment. RESULTS: There was an increase in average corneal astigmatism over
      two years of 2.2 diopters in the adjusted group and 1.7 diopters in the non
      adjusted group with sutures in place. One year following surgery, average
      keratometry flattened from 47.5 to 42.9 diopters in the adjusted continuous group
      and from 47.0 to 46.0 diopters in the group with combined continuous and
      interrupted sutures. Following suture removal, average astigmatism in patients
      who had suture adjustment was 4.4 diopters +/- 2.5 diopters (range 1-10
      diopters), and 6.01 diopters (range 4-7) in the non-adjusted group. CONCLUSIONS:
      Average post keratoplasty astigmatism increases after a continuous suture is
      adjusted but the increase is comparable to patients with acceptable astigmatism
      who do not require adjustment. More progressive corneal flattening over 12 months
      time is seen with a continuous suture than which combined sutures. Average suture
      out astigmatism was 4.0 diopters following suture adjustment, compared to an
      average of 8.4 diopters prior to adjustment.

PMID- 8981722
TI  - ISBT Code 128 and code changes as part of the implementation of a national IT
      system for the English National Blood Service.
AB  - The implementation of PULSE within the NBS will bring considerable advantages to
      the Service and to hospitals. A system of dual labelling has been developed to
      overcome intrinsic constraints identified with the ABC Codabar system. This
      should not, however, impact directly on hospitals which will be able to continue
      to utilize the ABC Codabar system. The dual labelling system incorporates the use
      of the ISBT Code 128 barcode system for transfusion centre use. This must be
      clearly differentiated from the implementation of ISBT code 128 within the UK.
      This latter development would bring considerable benefit to transfusion practice,
      increasing the overall safety of blood transfusion. It is, however, recognized
      that extensive discussion with appropriate stakeholders will be necessary before
      any implementation date can be determined for this initiative, particularly so
      given the significant logistical and financial implications inherent in such a
      change.

PMID- 8981723
TI  - Allogeneic vs. autologous blood transfusion: can a meta-analysis shed any light?

PMID- 8981724
TI  - Can pooled red cells be used for antibody screening of patients' specimens?

PMID- 8981725
TI  - Variation in the sensitivity of HBsAg screening kits.
AB  - Fifteen HBsAg kits from 14 manufacturers were assessed. Their sensitivity was
      evaluated by testing 150 HBsAg-positive sera, sera from four donors who were low
      level HBsAg carriers, and sequential specimens from 22 seroconverting individuals
      together with dilutions of six of these specimens. The British HBsAg Working
      Standard (0.5 IU mL-1) and the NIBSC/UKBTS HBsAg Monitor Sample (0.125 IU mL-1)
      were also tested. Five assays failed to detect one of the 150 routine HBsAg
      positive sera. Four assays (Auszyme Monoclonal; Monolisa Ag HBs 2nd generation;
      Murex HBsAg; Ortho HBsAg Test Systems 3) were able to detect HBsAg in all but one
      of the six sera from low-level carriers, whereas one assay (MicroTrak II HBsAg)
      detected only one of the six. The most sensitive kit (Monolisa Ag HBs 2nd
      generation) detected HBsAg in 79 specimens from the seroconversion panels; four
      other kits detected HBsAg in at least 70 specimens, seven in 60-69, two in 50-59
      and the least sensitive in 31. Further analysis of the findings on seroconverters
      indicated a median reduction in the duration of HBsAg detection of 5 days or more
      for four assays when compared with the most sensitive assay. One kit (Auszyme
      Monoclonal) detected HBsAg in 15 of the 18 dilutions prepared from the
      seroconversion specimens, whereas three kits detected HBsAg in fewer than 10
      dilutions. Two kits gave negative reactions with the British HBsAg Working
      Standard on all of five occasions and six were consistently unreactive with the
      NIBSC/UKBTS HBsAg Monitor Sample; only three kits (Bioelisa, Enzygnost, Murex)
      were always reactive. There is therefore substantial variation in sensitivity
      among the HBsAg kits currently available.

PMID- 8981726
TI  - Dried sera for confirming blood-borne virus infections (HCV, HTLV-I, HIV &
      HBsAg).
AB  - For safe blood transfusion, developing countries face considerable problems
      including serological screening and confirmation of blood-borne virus infections
      (HCV, HTLV-I, HIV and HBsAg). Confirmation tests are not only costly but also
      require sophisticated techniques and expertise. In order to provide this support
      we have attempted to perform a virus antibody confirmation test on samples dried
      on blotting paper (BP). Forty-nine sera derived from selected patients and donors
      from Bombay, and nine donors' sera from Bellarussia were transported on BP. In
      control experiments, dilutions of antibody-positive sera (HIV, HTLV-I & HCV) and
      'blinded' HTLV-I antibody-positive and antibody-negative donors were applied on
      BP. Eluates from snipped BP were tested initially by screening tests, and the
      reactives were subjected to confirmatory tests for three types of virus antibody
      tests (HCV, HTLV-I & HIV) by blotting methods and neutralisation tests for HBsAg.
      There was considerable reduction of titres in dry sera but all BP-derived dry
      specimens gave excellent qualitative concordance with their liquid-equivalent
      sera, and the HTLV-I-positive donor was identified and reconfirmed correctly.
      Presence of only HCV antibody was confirmed in all the nine selected Bellarussian
      donors. Blood donors in Bombay had 3% HIV antibody, 6% HBsAg and none had HCV
      antibody, while selected patients showed substantially higher levels of these
      markers: HIV-antibody 64%, HBsAg 57% and HCV-antibody 17% confirmed positive. The
      cause of this high level remains to be established. Dry samples received by post
      seem to be an economical approach to a first step in providing some levels of
      independent confirmation of reactives in developing countries.

PMID- 8981727
TI  - Differences in post-operative infection rates between patients receiving
      autologous and allogeneic blood transfusion: a meta-analysis of published
      randomized and nonrandomized studies.
AB  - We have undertaken a meta-analysis of the post-operative infection rates in
      patients who received autologous blood compared with allogeneic blood. Nine
      studies published after 1989 were identified, of which seven had sufficient data
      on transfusion given in the paper to be included, giving a total of 1060
      patients. The risk of post-operative infection was greater in the allogeneic
      group, odds ratio 2.37 (95% confidence interval (CI) 1.6-3.6, P < 0.0001)
      compared with the autologous group. Allogeneic and autologous blood transfusion
      should be compared in a large multicentre randomized control trial.

PMID- 8981720
TI  - Vision in albinism.
AB  - PURPOSE: The purpose of this investigation was to study vision in albinism from 3
      perspectives: first, to determine the characteristics of grating acuity
      development in children with albinism; second, to study the effect of
      illumination on grating acuity; and third, to define the effect of melanin
      pigment in the macula on visual acuity. METHODS: I. Binocular and monocular
      grating acuity was measured with the acuity card procedure in 40 children with
      albinism during the first 3 years of life. Recognition acuity was eventually
      measured in 27 of these patients. Ocular pigment was documented by a previously
      established method of grading iris transillumination and macular transparency.
      II. Grating acuity under standard and increased illumination levels was measured
      in 20 adults with albinism (group I) compared with that in 20 adults with
      nystagmus due to conditions other than albinism (group II) and 20 adults without
      ocular abnormalities (group III). Recognition acuity measured with the ETDRS
      charts was also recorded for each group. III. Best-corrected binocular acuity was
      measured in 29 patients with albinism who were identified with melanin pigment in
      their maculas by direct ophthalmoscopy. RESULTS: I. Both binocular and monocular
      grating acuity was reduced 2 to 3 octaves below the norm for ages 6 months to 3
      years. Limited data available in the first 6 months of life did not show failure
      of vision to develop. Grating acuity measurements overestimated eventual
      recognition acuity. Mean recognition acuity was 20/111. A relationship between
      grating acuity development and presence or absence of ocular pigment was not
      found. II. Grating acuity was significantly better for groups I and II under the
      condition of increased illumination (P < .03). For patients with albinism,
      grating acuity under standard illumination was significantly better than
      recognition acuity (P < .001). For all groups, grating acuity under increased
      illumination was significantly better than recognition acuity (P < .01). III.
      Mean recognition acuity in patients with albinism and melanin pigment in their
      maculas (20/47) was significantly better than measured recognition acuity in
      Project I (P < .001). All had foveal hypoplasia, but 8 patients had an
      incompletely developed annular reflex in the macula, 6 patients showed
      stereoacuity, and 3 patients had no nystagmus. CONCLUSIONS: I. Grating acuity
      development in albinism seems to progress along a curve that is asymptotic to
      visual development in a normal population. II. Increasing illumination does not
      reduce grating acuity in patients with albinism. Grating acuity overestimates
      recognition acuity in these patients. III. Ophthalmoscopic detection of melanin
      pigment in the macula in patients with albinism is associated with better vision.

PMID- 8981728
TI  - Lymphocyte phenotypes and infection incidence in transfused preterm neonates.
AB  - The immunomodulating effects of repeated exposure to blood from multiple donors
      coupled with an immature immune system may predispose the preterm neonate to an
      increased incidence of infection in his first few months of life. To test this
      hypothesis, we compared lymphocyte phenotypes, serum IgG concentrations, and
      histories of infection and rehospitalization in neonates at 4 months corrected
      age. Two of the study groups were preterm infants who had been transfused with
      either frozen, deglycerolized or CMV-negative, gamma-irradiated blood. Control
      groups consisted of nontransfused term and preterm infants. There were no
      differences found in lymphocyte phenotypes or serum IgG concentrations of
      controls or transfused infants. No differences were found in the infection or
      rehospitalization incidence in the transfused infants as compared with
      nontransfused preterm neonates. We failed to show differences in immune
      parameters or in infection and rehospitalization rates of the preterm infants
      analysed. Alongside previously published reports, our data suggest that red cell
      transfusions have a minimal impact on the immature immune system of the neonate.

PMID- 8981729
TI  - Rapid detection of the cisAB allele consisting of a chimera of normal A and B
      alleles by PCR-RFLPs.
AB  - DNA samples were analysed from Japanese individuals with the very rare ABO
      variant phenotype, cisAB (A2B3), which is characterized by the apparent
      inheritance of both A and B genes on one chromosome. The nature of the bases
      present at nucleotide positions (nps) 261, 526, 703, 796 and 803 is important for
      the specificity of the alleles at the ABO locus and the DNA from the cis AB
      donors was analysed by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) to determine which nucleotides are present at these
      positions. The results indicated that the cisAB allele had the AAAB-structure,
      which was a chimera of normal A and B alleles, when the expression 'AAAA' and
      'BBBB' indicated the nucleotides of normal A (C, G, C and G) and B (G, A, A and
      C) genes at nps 526, 703, 796 and 803, respectively. The AAAB allele was found in
      all 27 individuals (17 families) with the cisAB including three phenotypes A2B3,
      A1B3 and A2B and no other chimeric gene was found. The causative gene of cisAB
      was the AAAB allele, and the A and B alleles were not on one chromosome. The
      cisAB allele appeared to be a product of the normal A allele due to a point
      mutation at nucleotide position 803, from G to C. The AAAB allele is thought to
      be normally transcribed and translated to produce an unusual transferase
      polypeptide, which has weak A- and weaker B-specific activity. PCR-RFLP is a
      rapid and useful means of detecting the cisAB allele (the AAAB allele) without a
      family study, even when they have A1B3 and A2B phenotypes, because trans-type
      A1B3 and A2B samples have obviously different PCR-RFLP profiles.

PMID- 8981730
TI  - The use of pooled red cells and column techniques for routine red cell antibody
      detection.
AB  - The object of antibody screening is to detect all clinically relevant antibodies.
      In order to do this effectively red cells are selected with an appropriate
      antigen profile. The introduction of column techniques for antibody screening by
      indirect antiglobulin testing (IAT) and two-stage enzyme testing (ETC) is
      perceived to lead to an increased sensitivity and an ability to detect red cell
      antibodies more easily than by traditional tube techniques because reactions in
      columns are more easily read and are stable. We evaluated the use of a column
      technology with pooled red cells for routine antenatal screening. The pooled
      cells used contained at least one cell with homozygous antigen expression for the
      majority of clinically significant antibodies known to be present, except for
      Kell. Pooled cell results were not as easy to read in gel columns when compared
      with single cell results due to weaker reactions which were often diffused
      throughout the gel in the column. We concluded that the use of pooled cells led
      to a decreased sensitivity which proved problematic for the interpretation of
      results. We used a two-cell and a three-cell pool and found that detection of
      known antibodies was reduced in IAT and ETC methods.

PMID- 8981731
TI  - The incidence of anti-Wra and Wra antigen in blood donors and hospital patients.
AB  - A retrospective study of positive 37 degrees C indirect antiglobulin test (IAT)
      for compatibility following negative antibody screens in a hospital laboratory
      revealed an unexpectedly high incidence of Wra-incompatible units. Over the
      course of 1 month 1112 routine patients' samples containing no other atypical
      antibodies were tested for the presence of anti-Wra. Anti-Wra was found in 88
      patients, an incidence of 7.9%. Testing of 5098 healthy blood donor samples found
      54 donors positive for anti-Wra, an incidence of 1.06%. A survey of 5253 healthy
      blood donor samples for Wra antigen found only two Wra-positive samples,
      suggesting an incidence between 1 in 1000 and < 1 in 10,000. The significance of
      this finding is discussed in relation to the continuing use of an IAT
      compatibility test.

PMID- 8981732
TI  - Wooldridge Memorial Lecture. Structure and function in veterinary education: can
      what we have deliver what we want?

PMID- 8981733
TI  - Relevance of abattoir hygiene assessment to microbial contamination of British
      beef carcases.
AB  - Eleven beef abattoirs were visited, each on five separate occasions. On each
      occasion, an audit was carried out according to the official Hygiene Assessment
      System (HAS) and 10 carcases were sampled at four different sites to assess total
      viable counts and counts of presumptive coliform bacteria. The HAS scores ranged
      from 11 to 84 (maximum 100), and the logarithmic mean total viable counts for all
      sampling sites on each batch of carcases varied between 1.98 and 4.14 colony
      forming units/cm2. The mean prevalence of coliform contamination ranged from 0 to
      85 per cent. There was a significant negative correlation (P < 0.001) between the
      mean HAS scores and the mean total viable count for each abattoir, but not
      between the HAS scores and the numbers of coliforms. Within the HAS, the mean
      scores for all five categories, before weighting, showed a significant
      correlation with the mean total viable count (P < 0.001); however, the categories
      concerned with slaughter and dressing, and personnel and practices were of most
      value in determining trends in carcase contamination. A new advisory
      classification is proposed for levels of microbial contamination on beef
      carcases.

PMID- 8981734
TI  - Survey of feather diseases of exhibition budgerigars in the United Kingdom.
AB  - Breeders of exhibition budgerigars have commented for some years on an increasing
      prevalence of feather diseases in their birds. A survey of these diseases
      identified 37 different conditions, but three-quarters of the cases were due to
      only four conditions: psittacine beak and feather disease, pulpitis, feather
      mites and feather cysts.

PMID- 8981735
TI  - Reproductive and financial impact of a do-it-yourself artificial insemination
      programme compared with keeping a bull.
AB  - The fertility of five dairy herds was studied for three years while they
      initiated a programme of do-it-yourself artificial insemination (DIY AI) and kept
      a herd bull, and the financial impact of the new programme was assessed. The
      herds of approximately 100 cows were all Friesian pedigree, changing to
      Friesian/Holstein. The DIY inseminators each operated within one herd and were
      all trained at the same centre. Within a herd, each cow inseminated by a bull was
      paired with a cow inseminated by AI. The paired cows calved during the same week
      and were of the same lactation number and genetic type. Each year 20 matched
      pairs, that is 40 cows per herd, were used, giving a total of 600 cow records.
      During the first two years, in the majority of herds the calving interval
      decreased in both the cows inseminated by DIY AI and by the bull. There was a
      higher culling rate for all cows in the first year, resulting in an improved
      Fertex score and improved profitability in the second year compared with the
      first. However, in the five herds combined it was only by the third year that the
      calving interval for the DIY AI cows was shorter (by 17.9 days) than for cows
      inseminated by the bull (P < 0.05). The first year of the DIY AI programme was a
      financial strain for the farmers, but the second and third years showed enough
      improvement to recover the losses incurred in initiating DIY AI, that is, the
      capital investment and learning period.

PMID- 8981736
TI  - Control of sheep scab (Psoroptes ovis) by a single prophylactic injection of
      moxidectin.

PMID- 8981737
TI  - Stillbirth/perinatal weak calf syndrome: radiographic examination for growth
      retardation lines.

PMID- 8981738
TI  - Hepatitis in a European brown bear with canine infectious hepatitis-like lesions.

PMID- 8981740
TI  - Teeth trimming in rabbits and rodents.

PMID- 8981739
TI  - Teeth trimming in rabbits and rodents.

PMID- 8981741
TI  - Teeth trimming in rabbits and rodents.

PMID- 8981742
TI  - Rabies and quarantine.

PMID- 8981743
TI  - Rabies and quarantine.

PMID- 8981744
TI  - Rabies and quarantine.

PMID- 8981745
TI  - Casein kinase II activity in the brain of an insect, Acheta domesticus:
      characterization and hormonal regulation.
AB  - This study documented casein kinase II (CK II) activity in Acheta domesticus
      brain using specific antibodies and its regulation by polyamines. In control
      animals a transient decrease in CK II activity at day 3 after imaginal moult was
      observed in the brain but not in the fat body. If deprived of ecdysone by
      ovariectomy a different pattern was observed, with CK II activity being
      significantly higher on days 3 and 4 after emergence. After ecdysone injection in
      ovariectomized females, CK II activity decreased to levels similar to those in
      controls. The implications of ecdysone regulation of brain CK II activity are
      discussed.

PMID- 8981746
TI  - Prionics or the kinetic basis of prion diseases.
AB  - A comparative kinetic analysis of mechanisms of prion diseases based on the
      "protein only" hypothesis is presented. The Prusiner mechanism of autocatalytic
      conversion of a host protein into a genetically identical, but conformationally
      different, prion state requires cooperativity in order to work, given realistic
      values of rate parameters. It then becomes phenomenologically indistinguishable
      from the Lansbury mechanism of plaque formation which is also a form of (passive)
      autocatalysis. Though the two kinds of mechanisms still may differ on the
      question which of the two monomeric protein conformations is the favoured
      equilibrium state they both require an aggregated state as the form that is
      eventually favored at equilibrium. While these considerations allow for a
      critical comparison of the mechanisms they do not yet tell us what the actual
      mechanism of infection is. Experiments rather indicate that the infectious unit
      in vivo may still differ from an in vitro form of aggregated prion proteins.
      Hence aggregation of the prionic form is most probably a necessary, but possibly
      not sufficient, prerequisite of infection. Be that as it may, the premise of a
      linkage between prion aggregation and infection offers a very sensitive method
      for diagnosing the disease at a very early stage, using fluorescence cross
      correlation analysis. The possible analogies to Alzheimer's disease make such a
      prospect a "hot topic".

PMID- 8981747
TI  - Characterization of Eu(III) binding to a series of calmodulin binding site
      mutants using laser-induced Eu(III) luminescence spectroscopy.
AB  - Laser-induced luminescence techniques were used in a rigorous evaluation of the
      Eu(3+)-binding behavior of a recombinant (Drosophila melanogaster) calmodulin and
      a series of calmodulin binding site mutants in which the bidentate glutamic acid
      residue in position 12 of each metal ion binding loop is systematically replaced
      with lysine. For the range of Ca2+ concentrations at which calmodulin functions
      (10(-5)-10(-6) M), Ca2+ binding is effectively eliminated at the mutated site;
      however, the luminescence studies show that the Eu3+ ion binds to the modified
      site with reduced affinity. The mutations do not significantly change the
      intermetal ion distances from their wild type values. These were determined by
      Eu3+-->Nd3+ Forster-type non-radiative energy transfer experiments. Consistent
      with the results of Ca(2+)-binding studies, mutation of sites II and IV in the N-
      and C-terminal domains, respectively, produces a larger alteration in the Eu(3+)
      luminescence and Eu(3+)-binding behavior than does mutation of sites I and III.
      Modification of either of the sites in the C-terminus (III or IV, numbered from
      the amino terminus) causes two additional H2O molecules (four H2O molecules
      total) to bind to the Eu3+ ion in order to compensate for the loss of the
      bidentate glutamic acid residue. Consequently, the partner site in the domain
      loses an H2O molecule, thereby coordinating another ligand from the protein.
      Mutation of either of the high-affinity Ln(3+)-binding sites (I or II) has global
      effects on the Eu(3+)-binding behavior of the protein molecule.

PMID- 8981748
TI  - Histidine-tryptophan interactions in T4 lysozyme: 'anomalous' pH dependence of
      fluorescence.
AB  - A variant of T4 lysozyme which contains only a single tryptophan residue (at
      position 138) has been prepared (W126Y/W158Y designated 'YWY'). Two additional
      mutations to YWY have been prepared involving replacement of glutamine 105, which
      hydrogen bonds to the indole N-H of trp 138 in wild type, with either a histidine
      (YWY/Q105H) or an alanine (YWY/Q105A). The fluorescence properties of these two
      species are investigated as a function of pH. YWY/Q105A exhibits essentially a
      single exponential fluorescence decay (5% tau = 0.35 ns 95% tau = 5 ns) and
      almost no pH dependence in steady state or time resolved fluorescence behavior.
      In contrast, YWY/Q105H exhibits complex fluorescence decay over the entire pH
      range used in these experiments. As the pH is lowered from 8 to 4, there is an
      increase in the quantum yield and a change in the average lifetime (from 2.0 to
      3.1 ns). Using this data, the pKa of histidine 105 has been determined to be 5.9.
      These results are contrasted to those from other proteins which show a pH
      dependent tryptophan fluorescence associated with a neighboring histidine or
      other residue. Quenching behavior in terms of the stereochemistry of the
      tryptophan-histidine interaction and implications of these results for current
      models of complex fluorescence behavior of single tryptophan proteins are also
      discussed.

PMID- 8981749
TI  - The existence of a hexameric intermediate with molten-globule-like properties in
      the thermal denaturation of bovine-liver glutamate dehydrogenase.
AB  - We have studied the thermal denaturation of hexameric beef-liver glutamate
      dehydrogenase by itself and in the presence of ADP and guanidine-HCl by a variety
      of techniques. In differential scanning calorimetry studies, the observed melting
      temperature and total enthalpy of denaturation show no dependence on protein
      concentration, but do show significant dependence on the scan rate. This suggests
      that the overall denaturation process is irreversible and kinetically controlled.
      Isothermal unfolding kinetics from spectrophotometry confirm this result. The
      size of the protein, as shown by quasi-elastic light scattering measurements,
      does not change during the denaturation process. We interpret these results in
      terms of the following model: N6 reversible N'6-->6U(-->F) where N6 and N'6 are,
      respectively, the native hexamer and a hexameric, highly folded high-enthalpy
      species, U is the unfolded monomer and F is some final aggregated state. The
      kinetic intermediate, N'6, possesses the properties of one definition of a molten
      globule, having a very high enthalpy and a hexameric compact structured form.
      This "molten globule" is an obligatory intermediate in the unfolding pathway of
      the protein. The stabilization of the protein by ADP is due to the modulation of
      the high-enthalpy two-state predenaturational E reversible E' transition,
      resulting in the lowering of the energy of the native state of the protein.

PMID- 8981750
TI  - The binding of Violamycin BI to poly-C.
AB  - The binding constant Kst of Violamycin BI (VBI) to poly-C at small and medium
      values of the concentration ratio p (0-12) is determined using the procedure of
      Schwarz under two different conditions: at constant C(VBIo) and variable C(po),
      and at p = C(po)/C(VBIo) = const. The average value obtained for Kst is 3.3 +/-
      0.1 x 10(4) M-1, whereas the cooperativity parameter q of 13 characterizes a
      moderate cooperative interaction between adjacent bound ligands. In contrast, at
      large values of p (12-355) the formation of isolated bound dimers on the poly-C
      chain is observed. At pH 7, VBI dimerizes in solution with a dimerization
      constant strongly dependent on ionic strength: Kd = 732 +/- 20 M-1 and (9.3 +/-
      0.2) x 10(3) M-1 at I = 0.02 M and 0.2 M respectively. The lower and upper
      boundaries for the binding constant of the dimer to the polynucleotide at large
      values of p are 1.0 x 10(-5) M-1 and 6.25 x 10(-6) M-1 respectively.

PMID- 8981751
TI  - Optical activity of a nucleotide-sensitive tryptophan in myosin subfragment 1
      during ATP hydrolysis.
AB  - The xanthene probes 5'-iodoacetamido-fluorescein and -tetramethylrhodamine
      specifically modify skeletal muscle myosin subfragment 1 (S1) at the reactive
      thiol residue (SH1) and fully quench the fluorescence emission from tryptophan
      residue 510 (Trp510) in S1 (T.P. Burghardt and K. Ajtai, Biophys. Chem., 60
      (1996) 119; K. Ajtai and T.P. Burghardt, Biochemistry, 34 (1995) 15943). The
      difference between the fluorescence intensity obtained from S1 and probe-modified
      S1 comes solely from Trp510 in chymotryptic S1, a protein fragment that contains
      five tryptophan residues. The rotary strength and quantum efficiency of Trp510
      were measured using difference signals from fluorescence detected circular
      dichroism (FDCD) and fluorescence emission spectroscopy. These structure
      sensitive signals indicate that the binding of nucleotide or nucleotide analogs
      to the active site of S1 causes structural changes in S1 at Trp510 and that a one
      to-one correspondence exists between Trp510 conformation and transient states of
      myosin during contraction. The Trp510 rotary strength and quantum efficiency were
      interpreted structurally in terms of the indole side-chain conformation using
      model structures and established computational methods.

PMID- 8981752
TI  - No-donors: an emerging class of compounds in medicinal chemistry.

PMID- 8981753
TI  - 7-(N-substituted)amino-2,3-polymethylene benzofurane derivatives with tracheal
      relaxant activity.
AB  - A set of twelve 7-(N-substituted)amino-2,3-polymethylenebenzofuranes (1-12)
      together with three related compounds (13-15) was prepared. Ten selected
      compounds were tested for tracheal relaxant activity in vitro and two of them
      (6,7) were also subjected to a broad pharmacological screening. Five compounds
      (2,7,9,12,14) at the concentration of 30 micrograms/ml exhibited high tracheal
      relaxant activity (73-94% tone reduction) that was superior than that of
      theophylline at the same concentration. The 7-(N-trifluoromethylsulfonyl)amino
      2,3-tetramethylenebenzofuran e (9) was highly active till the concentration of 1
      microgram/ml giving a stronger tracheal relaxation than amrinone at 3
      micrograms/ml. On the other hand the general screening did not show any other
      major activity. The benzofurane derivatives 1-13 were obtained through obvious
      steps from the corresponding 7-nitrobenzofuranes, which were prepared by a
      Fischer indole-like cyclization of O-[(2-nitro)phenyl] ketone oximes. In one case
      two peculiar side products were isolated.

PMID- 8981754
TI  - Synthesis and microbiological evaluations of (N-heteroaryl) arylmethanamines and
      their Schiff bases.
AB  - The synthesis as well as the antimicrobial and antiviral activities of new (N
      heteroaryl)arylmethanamines and their Schiff bases are reported. None of the
      tested compounds shown activity against Herpes simplex virus type 2 and against
      Gram positive and Gram negative bacteria. Weak or moderate activity on poliovirus
      Sabin type 1, on reverse transcriptase and against Cryptococcus neoformans was
      shown by some of the tested compounds. Viceversa several synthesized compounds
      exhibited a moderate or good activity against strains of Candida albicans, while
      only some of the tested compounds were found moderately active against strains of
      Candida sp. Instead numerous new compounds 3 or 4 were active as control against
      isolates of plant pathogenic fungi. The obtained results are discussed on the
      basis of structure-activity relationships.

PMID- 8981755
TI  - Synthesis and pharmacological evaluation of 5,6-dihydrobenzo[f] cinnolin
      2(3H)ones analogues of antihypertensive and antiaggregating benzo[h]cinnolinones.
AB  - Two new dihydrobenzo[f]cinnolin-2(3H)ones (4a,b) have been synthesized and tested
      for their hypotensive, antihypertensive and antiaggregating activities in
      comparison with the lead 8-acetylamino-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)
      one 1. In vivo tests indicated that 4a,b displayed hypotensive and
      antihypertensive properties weaker than the model compound. On the contrary both
      compounds were more potent than 1 in inhibiting collagen-induced platelet
      aggregation.

PMID- 8981756
TI  - 3,6-Disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles: synthesis,
      antimicrobial and antiviral activity. II.
AB  - A series of novel 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4] thiadiazole
      derivatives was prepared and tested to evaluate their antimycotic and
      antibacterial activities. Anti-HIV-1 activity has also been investigated. Among
      the test compounds, derivatives 10a-14a and 16c showed anti-HIV-1 activity at
      concentrations slightly below those cytotoxic. Substitutions at 3 and 6 positions
      seems to be important in lowering the cytotoxicity of compounds.

PMID- 8981757
TI  - Synthesis and pharmacological activity of some N,N-disubstituted 1-amino-2-phenyl
      3H,12H-naphtho[1,2-b]pyrano[2,3-d]pyran-3-ones.
AB  - The synthesis of some N,N-disubstituted 1-amino-2-phenyl-3H,12H-naphtho[1,2
      b]pyrano[2,3-d]pyran-3-ones 4, by reaction of phenylchloroketene with a series of
      N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-naphtho[1,2-b]pyran-4-ones,
      followed by dehydrochlorination in situ of the primary adducts with DBN, is
      described. Some compounds 4 showed antiarrhythmic and analgesic activities.

PMID- 8981758
TI  - Synthesis and local anesthetic activity--lipophilicity relationships for a
      homological series of phenylcarbamic acid esters. Note II.
AB  - A homological series of new esters of 2-alkoxyphenylcarbamic acid and one ester
      of 2,6-dimethylphenylcarbamic acid were synthesized and assayed for surface local
      anesthetic activity. All compounds were isolated as hydrochlorides and their
      structure proved by IR and for one homologue also by 1H and 13C NMR spectroscopy.
      A parabolic relationship was found between log activity and molecular
      lipophilicity (as measured by RM) and the number of carbons in the alkoxy group,
      thus confirming the results obtained in previous works.

PMID- 8981759
TI  - Heart rate during development in the turtle embryo: effect of temperature.
AB  - Growth and development can occur over a wide range of physical conditions in
      reptiles. Cardiovascular function must be critical to this ability. However,
      information on cardiovascular function in developing reptiles is lacking.
      Previous work indicated that in reptiles the effects of temperature on growth and
      metabolism are largely restricted to early development. This study examined
      whether the previously observed effects of temperature and different perinatal
      patterns of metabolism observed in amniotic vertebrates are correlated with
      cardiovascular function. Embryonic and hatchling carcass mass, heart mass and
      heart rate (HR) were compared for snapping turtle eggs (Chelydra serpentina)
      incubated at 24 degrees and 29 degrees C. Incubation time was shorter at 29
      degrees C (56.2 days) than at 24 degrees C (71.1 days). Carcass and heart growth
      showed a sigmoidal pattern at both temperatures. However, cardiac growth showed a
      relative decrease as incubation proceeded. Incubation temperature significantly
      affected the HR pattern during development. The HR of embryos incubated at 24
      degrees C was constant for most of incubation (51.8 +/- 4.8 min-1). A small
      decrease was observed just prior to and a large decrease immediately following
      hatching (posthatch, 22.3 +/- 4.1 min-1). At 29 degrees C embryonic HR was
      greater than at 24 degrees C early in development (72.3 +/- 3 min-1). The HR
      steadily decreased to values equivalent to those at 24 degrees C. The HRs of 24
      degrees C and 29 degrees C hatchlings were not different. Cardiac output
      (estimated as the product of heart mass and HR) increased rapidly during early
      development and then slowed dramatically at both temperatures. These data are
      consistent with the suggestion that temperature exerts its effects primarily
      early in development. Furthermore, the changes in cardiovascular function are
      correlated with metabolic changes in hatching vertebrates.

PMID- 8981760
TI  - Inhibition of goby posterior intestinal NaCl absorption by natriuretic peptides
      and by cardiac extracts.
AB  - Natriuretic peptides abolish active Na+ and Cl- absorption across the posterior
      intestine of the euryhaline goby Gillichthys mirabilis. Inhibition by eel and
      human natriuretic peptides is dose-dependent with the following sequence of
      potencies based on experimentally determined ID50 values for inhibition of short
      circuit current: eel ventricular natriuretic peptide (78 nmol.l-1), eel atrial
      natriuretic peptide (156 nmol.l-1), human brain natriuretic peptide (326 nmol.l
      1), human alpha atrial natriuretic peptide (1.05 mumol.l-1), and eel C-type
      natriuretic peptide (75 mumol.l-1). Natriuretic peptides also significantly
      increase transcellular conductance. The observed sequence of natriuretic peptide
      potencies is suggestive of cellular mediation by GC-A-type NP-R1 receptors in
      this tissue; as expected for guanylyl-cyclase-coupled NP-R1 receptors, cyclic GMP
      mimics the action of natriuretic peptides on the goby intestine. Crude aqueous
      extracts of goby atrium and ventricle inhibited short circuit current and
      increased tissue conductance in a dose-dependent manner. Ventricular extract was
      more potent than atrial extract on both a per organ and per milligram basis.

PMID- 8981761
TI  - The supercooling ability of ticks (Acari, Ixodoidea).
AB  - The supercooling capacity of nine laboratory-held species of ticks originating
      from different geographical areas, as well as five field-collected species from
      Germany, was investigated. All but one tick species showed mean supercooling
      points between about -17 and -23 degrees C, suggesting that the capacity to
      supercool to temperatures of < or = -17 degrees C might be an inherent property
      of many tick species unrelated to their geographic origin. Photoperiod did not
      influence the mean supercooling point in any of the species and there was also no
      distinct seasonal pattern of supercooling in seasonally acclimatized Dermacentor
      marginatus. Thus, the supercooling ability was independent of the
      presence/absence of diapause. The finding of thermal hysteresis in D. marginatus
      hemolymph raises the question of whether or not anti-freeze proteins are involved
      in the supercooling capacity of that species. An interspecies comparison revealed
      a weak negative correlation between relative water content and supercooling point
      of the ticks and an even weaker correlation between body mass or body water mass
      and the supercooling point. Since the ticks exhibited low supercooling points
      both before and shortly after feeding, the blood used as food should lack potent
      ice nucleators.

PMID- 8981762
TI  - Insecticide resistance genes in mosquitoes: their mutations, migration, and
      selection in field populations.
AB  - Insecticides have been used intensively to control insect populations over the
      last 50 years and many species of insects have developed resistance to several
      families of insecticides. These resistances are mainly due to two mechanisms:
      mutation of the insecticide target protein (leading to a decrease in its affinity
      for the concerned insecticide family), and increased detoxification. Recent
      molecular studies suggest that the mutations conferring resistance are rare and
      sometimes unique events in any given species. The wide geographic distribution of
      some of these genes can then only be explained by the balance between migration
      and selection at the population level.

PMID- 8981763
TI  - Arbitrary primer PCR of dog DNA with estimates of average heterozygosity.
AB  - Arbitrary primer polymerase chain reaction (AP-PCR) detected anonymous DNA
      polymorphisms between individual representatives of seven breeds of dogs, between
      members of a single breed, and between members of a single family of dogs. Short
      arbitrary sequence PCR primers and promoter/protein motif sequence primers
      typically amplified 15-30 bands ranging from 200-2000 bp in length. The average
      heterozygosity of 10 line bred Belgian sheepdogs (H = 0.024 +/- 0.011, mean +/-
      95% CI) was significantly lower than that of a panel of unrelated beagles (H =
      0.057 +/- 0.018, mean +/- 95% CI, P < .01). The average heterozygosity of a seven
      breed panel was intermediate between the two (H = 0.043 +/- 0.011, mean +/- 95%
      CI) and not significantly different than either panel. One motif sequence PCR
      primer pair yielded products that strongly differentiated between Belgian
      sheepdogs, beagles, and members of five other breeds. AP-PCR could be used to
      generate DNA fingerprints that distinguish between dog breeds, as well as to
      provide markers in this sparsely mapped genome.

PMID- 8981764
TI  - Heteroduplex mobility assays (HMAs) and analogous sequence analysis of a
      cytochrome b region indicate phylogenetic relationships of selected
      callitrichids.
AB  - Heteroduplex mobility assays (HMAs) of a cytochrome b region were used for
      estimating genetic distances and phylogenetic relationships between some selected
      neotropical primates of the families Callitrichidae (marmosets and tamarins) and
      Cebidae [capuchin monkey, (Cebus apella)], and man (Homo sapiens). HMA distances
      were found to be strongly correlated to analogous estimates derived from DNA
      sequence data. Phylogenetic trees obtained by HMAs and sequence analyses showed
      similar topologies with almost identical intraspecific, intrageneric, and
      intergeneric relationships. The applicability of HMAs is assessed relative to
      different levels of molecular and organismal diversity.

PMID- 8981765
TI  - Coat color alleles in the domestic cat populations at the Adriatic Coast.

PMID- 8981766
TI  - An analysis of genetic variation in Astragalus cremnophylax var. cremnophylax, a
      critically endangered plant, using AFLP markers.
AB  - A recently developed molecular technique (amplified fragment length
      polymorphisms, AFLP) was used for characterizing genetic heterogeneity within and
      among populations of a critically endangered species of plant, Astragalus
      cremnophylax var. cremnophylax. Using AFLP, up to 50 polymorphic genetic markers
      per AFLP-PCR amplification were generated, and a total of 220 variable markers
      overall. This information was used first to assess genetic diversity within each
      of the three known populations of Astragalus cremnophylax var. cremnophylax from
      Grand Canyon National Park in Arizona, USA: North Rim (NR; n = 970), South Rim
      Site 1 (SR1; n = 500), and South Rim Site 2 (SR2; n = 2). Diversity in the form
      of average heterozygosity [symbol: see text] H [symbol: see text] and the
      proportion of polymorphic genes [symbol: see text] P [symbol: see text] was
      greatest in the NR population ([symbol: see text] H [symbol: see text] = 0.13 and
      [symbol: see text] P [symbol: see text] = 0.38) and least in the SR2 population
      ([symbol: see text] H [symbol: see text] = 0.02 and [symbol: see text] P [symbol:
      see text] = 0.04). Diversity was also quite low for the SR1 population ([symbol:
      see text] H [symbol: see text] = 0.04 and [symbol: see text] P [symbol: see text]
      = 0.10). In addition, substantial genetic differentiation among populations was
      indicated by both phenetic (AMOVA) and genetic analyses (overall corrected FST =
      0.41). This finding was corroborated by the results of several multivariate
      analyses which utilized the genetic data, including a UPGMA cluster analysis and
      a principal coordinate analysis which revealed the existence of discrete groups
      corresponding to the populations. Population structure was further revealed
      within the NR population which was known to consist of four spatially separated
      groups of plants. Several recommendations for the future management of the
      species are discussed.

PMID- 8981767
TI  - Molecular genetic examination of the polymorphic Arctic charr Salvelinus alpinus
      of Thingvallavatn, Iceland.
AB  - Thingvallavatn, Iceland contains two sympatric morphotypes (benthic and limnetic)
      of Arctic charr Salvelinus alpinus. Each morphotype is composed of two morphs and
      these differ markedly in ecology, behaviour and life history. We used molecular
      genetic approaches to test whether (i) genetic heterogeneity exists among morphs
      and (ii) if morphs arose in allopatry and came into secondary contact or arose
      sympatrically within the lake through genetic segregation and/or phenotypic
      plasticity. Direct sequencing of 275 bp of the mitochondrial DNA (mtDNA) control
      region, mtDNA restriction fragment length polymorphisms and single locus
      minisatellite analyses detected insufficient variation to test our hypotheses.
      Analysis of multilocus minisatellite band sharing detected no significant
      differences between morphs within the same morphotype. However, significant
      differences among morphs belonging to different morphotypes suggest some genetic
      heterogeneity in Thingvallavatn charr. Limnetic charr from Thingvallavatn were
      more similar to sympatric benthic charr than to allopatric limnetics from two
      other Icelandic lakes. This suggests that the Thingvallavatn morphs arose
      sympatrically within the lake rather than in allopatry followed by secondary
      contact.

PMID- 8981768
TI  - Population and colony structure of the carpenter ant Camponotus floridanus.
AB  - The colony and population structure of the carpenter ant, Camponotus floridanus,
      were investigated by multilocus DNA fingerprinting using simple repeat motifs as
      probes [e.g. (GATA)4]. The mating frequency of 15 queens was determined by
      comparing the fingerprint patterns of the queen and 17-33 of her progeny workers.
      C. floridanus queens are most probably singly mated, i.e. this species is
      monandrous and monogynous (one queen per colony). C. floridanus occurs in all
      counties of mainland Florida and also inhabits most of the Key islands in the
      southern part of Florida. We tested whether the two mainland populations and the
      island populations are genetically isolated. Wright's FST and Nei's D-value of
      genetic distance were calculated from intercolonial bandsharing-coefficients. The
      population of C. floridanus is substructured (FST = 0.19 +/- 0.09) and the
      highest degree of genetic distance was found between one of the mainland
      populations and the island populations (D = 0.35). Our fingerprinting technique
      could successfully be transferred to 12 other Camponotus species and here also
      revealed sufficient variability to analyse the genetic structure. In three of
      these species (C. ligniperdus, C. herculeanus and C. gigas) we could determine
      the mating frequency of the queen in one or two colonies, respectively.

PMID- 8981769
TI  - Population differentiation and evolution in the common guillemot Uria aalge.
AB  - Common (Uria aalge) and Brunnich's guillemots (U. lomvia) are colonial seabirds
      that nest in temperate to arctic oceans throughout the Northern hemisphere. They
      are very similar in the characteristics of ecology, demography and life history
      that are thought to determine the extent of differentiation among populations,
      yet geographic variation in morphology is notably greater in common guillemots.
      Despite evidence of strong natal philopatry, previous analyses of allozymes and
      the mitochondrial cytochrome b gene revealed little genetic differentiation among
      North Atlantic colonies of Brunnich's guillemots. To determine if the more
      extensive morphological variability in common guillemots reflects greater genetic
      variability, we sequenced part of the cytochrome b gene for 160 common guillemots
      from 10 colonies distributed throughout the Northern hemisphere. Genotype
      frequencies and phylogenetic relationships among genotypes both indicated that
      Atlantic and Pacific populations are genetically distinct. Genetic divergence
      among genotypes suggested that differentiation of these populations has resulted
      from separation by Pleistocene glaciers and the Bering Landbridge, as well as by
      currently unsuitable breeding habitat in the Arctic Ocean. Cytochrome b genotype
      frequencies also differed among Atlantic colonies, and appeared to define a cline
      similar to that described for morphological characters. Analyses of sequence
      variation suggested that this variation probably results from secondary contact
      between two refugial populations from the Pleistocene glaciations, rather than
      from isolation by distance or selection. In contrast, the Atlantic population of
      Brunnich's guillemots appears to have arisen through recent expansion of a single
      homogeneous refugial population.

PMID- 8981770
TI  - Development and application of long-PCR for the assay of full-length animal
      mitochondrial DNA.

PMID- 8981771
TI  - Polymorphic microsatellite markers in the loggerhead shrike Lanius ludovicianus
      isolated from a library enriched for CA repeats.

PMID- 8981772
TI  - Cryptococcus neoformans var. gattii among patients with cryptococcal meningitis
      in Mexico. First observations.
AB  - A retrospective study of 20 patients with cryptococcal meningitis and their
      isolated strains was performed. Cryptococcus neoformans var. neoformans was
      recovered from 14 (70%) cases, and var. gattii was recovered from six (30%)
      patients. Twelve patients had AIDS (all carrying var. neoformans), two had other
      diseases (one with var. neoformans and one var. gattii) and there was no
      identifiable underlying disease in six (one var. neoformans and five var.
      gattii). Fourteen patients (11 var. neoformans and three var. gattii) resided in
      the Mexico City area, where a temperate climate is prevalent, and there were six
      cases (three var. neoformans and three var. gattii) from states with a
      tropical/subtropical climate. Although there was no significant statistical
      difference between the two varieties, the fatal outcome was higher in patients
      with var. neoformans. The disease caused by var. gattii strains was characterized
      by a higher opening pressure, more inflamatory changes of CSF and a longer
      clinical course (delayed clinical and mycological cure). Cryptococcus neoformans
      var. gattii is a significant cause of cryptococcal meningitis in patients without
      underlying diseases in Mexico.

PMID- 8981773
TI  - Candida biotypes in patients with oral leukoplakia and lichen planus. Candida
      biotypes in leukoplakia and lichen planus.
AB  - Prevalence of yeasts in 35 leukoplakia and 34 oral lichen planus patients was
      compared with that observed in persons without oral diseases. Serotype and
      morphotype were determined on Candida albicans isolates. Yeasts were isolated
      from the oral cavity specimens of 43.7% of the patients. C. albicans (serotype A)
      was the predominant species (76% in leukoplakia, 88.2% in lichen planus and 60.8%
      in healthy persons). Sixteen morphotypes were encountered on malt extract agar,
      being 732, 733, 734, 753 and 754 the most frequently found. Morphotypes SP1N and
      SP1Y were the most common on Sabouraud-trypheniltetrazolium agar (68.4% of the
      isolates from leukoplakia and 73.3% from lichen planus, but only 46.6% of the
      isolates from healthy oral mucosa showed SP1N morphotype). Presence of oral
      lesions was associated with a marked reduction in the yeast species and C.
      albicans biotypes, suggesting that C. albicans and particularly some of its
      biotypes, show a high potential of adaptation to the changes associated with the
      development of oral leukoplakia and lichen planus.

PMID- 8981774
TI  - Filamentous microfungi in raw flax and cotton for textile industry and their
      ciliostatic activity on tracheal organ cultures in vitro.
AB  - In a three-year experiment we studied mycobiota of 24 samples of flax and 45
      samples of cotton processed in Slovak textile factories. We isolated 12.2 x 10(6)
      (on average) cfu of microfungi per 1 g of flax samples and 3.3 x 10(5) (on
      average) cfu of micromycetes per 1 g of cotton samples. We also studied the
      ciliostatic activity of metabolites of isolated filamentous fungi on tracheal
      cultures of 1-day-old chicks in vitro. Twenty-nine percent of 116 investigated
      chloroform extracts of metabolites of microfungi isolated from flax samples
      stopped the cilia movement and 25% of 195 had ciliostatic activity during 72 h of
      experiment.

PMID- 8981775
TI  - Citrinin, ochratoxin A and iron. Possible implications for their biological
      function and induction of nephropathy.
AB  - Experiments with Neisseria meningitidis have shown that Fe3+ to some extent can
      reverse the toxicity of ochratoxin A and citrinin, as measured by inhibition
      zones around impregnated paper discs. Similar phenomena were observed with the
      less toxic ochratoxin B. Zearalenone also inhibited growth, but its effect was
      not counteracted by iron. The mycotoxins aflatoxin B1 and deoxynivalenol did not
      inhibit bacterial growth at all. Desferal (deferoxamine) also inhibited growth of
      meningococci, but iron totally abolished this inhibition. The results indicate
      that ochratoxin A and citrinin interfere with iron metabolism in this organism
      but that other additional toxic mechanisms are involved as well since a marked
      growth inhibition by both toxins was also observed in the presence of iron. One
      function of ochratoxin A and citrinin in nature could consequently be to affect
      the iron uptake of other competing microorganisms. Since both toxins interfere
      with iron and both cause nephropathy, a possible connection between these
      properties and lipid peroxidation is also briefly discussed.

PMID- 8981776
TI  - High incidence of Aspergillus flavus and aflatoxins in stored groundnut in Ghana
      and the use of a microbial assay to assess the inhibitory effects of plant
      extracts on aflatoxin synthesis.
AB  - Groundnut samples from 21 selected markets in the 10 regions of Ghana yielded
      high levels of the aflatoxigenic fungus Aspergillus flavus on half-strength
      potato dextrose agar. The fungus was associated with 31.7 and 12.8%,
      respectively, of all damaged and undamaged kernels assayed. Only 0.24% of total
      kernels assayed yielded A. parasiticus. Other fungi detected from total kernels
      assayed were A. niger (34%), A. candidus (1.45%), A. tamarii (3.93%), A.
      ochraceous (5.26%), Fusarium spp. (1.7%) Penicillium spp. (5.19%), a Mucor sp.
      (2.3%), a Trichoderma sp. (0.2%), Rhizopus stolonifer (12%) and certain
      unidentifiable fungi (11.72%). Total aflatoxin levels ranging from 5.7 to 22, 168
      ppb were identified with damaged kernel samples. The mycotoxin was not detected
      in 50% of undamaged kernel samples tested and very low levels mostly ranging from
      0.1 to 12.2 ppb were associated with the undamaged samples that tested positive
      for aflatoxins. In a novel in vitro microbial assay to determine the
      effectiveness of certain plant extracts against aflatoxin synthesis, extracts
      from Xylopia aethiopica, Monodera myristica, Cinnamomum verum and Piper nigrum
      permitted fungal growth in 1.5% potato-dextrose broth while completely
      suppressing NOR formation. These extracts, however, could not suppress NOR
      formation in a yeast extract sucrose medium.

PMID- 8981777
TI  - Synergy of human neutrophils with fluconazole in killing Candida species.
AB  - The killing of Candida species by human neutrophils in a long-term 24-h assay and
      possible synergy with fluconazole (FCZ) for killing was investigated. The test
      medium (TM) consisted of RPMI-1640, penicillin and streptomycin (P/S), and 10%
      fresh autologous serum. TM alone was highly fungistatic for Candida species
      compared to TM without serum. When neutrophils were cocultured in TM with Candida
      species for 24 h the inoculum colony-forming units (CFU) were always
      significantly reduced (killing) by 58 to 99%. FCZ was tested over a range of 1
      500 micrograms/ml, and though almost always fungistatic itself, it synergized
      with neutrophils for significantly increased killing of C. albicans (isolate
      Sh27) (P < 0.01) and C. albicans (isolate 94-20) (P < 0.05). Killing of non
      albicans Candida species was so efficient in the absence of FCZ that
      demonstration of synergy with FCZ was difficult.

PMID- 8981778
TI  - Phylogeny of Epidermophyton floccosum and other dermatophytes.
AB  - Eleven strains of Epidermophyton floccosum were compared with 5 Microsporum and 5
      Trichophyton species with respect to the restriction fragment length polymorphism
      (RFLP) of the mitochondrial DNA to reveal their phylogenetic relationships. The
      phylogeny of 11 species showed that the three dermatophyte genera could not be
      separated from each other and could be considered to be congeneric. This result
      is not inconsistent with the results from ribosomal RNA sequences.

PMID- 8981779
TI  - Isolation of fungi from the pelage of cats and dogs using the hairbrush
      technique.
AB  - A total of 178 cats and 59 dogs in Palmerston North, New Zealand were sampled for
      the presence of keratinophilic fungi on their pelage; 57.8% had fungi. The fungi
      were classified in 20 genera with the predominant species being members of the
      genera; Chrysosporium, Microsporum and Trichophyton. Cats were the major carriers
      of keratinolytic fungi. 18.5% of the cats and 5.1% of the dogs were either
      carriers or infected with M. canis. Microsporum canis was a frequent isolate and
      its distribution had a seasonal variation, with a peak appearing in May-June.

PMID- 8981780
TI  - Pseudotumoral presentation of chronic pulmonary paracoccidioidomycosis: report of
      a case.

PMID- 8981781
TI  - Developmental effects of fumonisin B1 in mice.
AB  - Developmental and toxic effects of aqueous extracts of F. moniliforme culture
      material containing known levels of fumonisin B1 were recently reported in mice
      and included maternal hepatotoxicity and lethality, maternal body weight gain
      reduction, increased embryonic resorptions, reduced offspring body weights, and
      fetal malformations including cleft palate, hydrocephalus, malformed ribs and
      incomplete digital and sternal ossification. These studies also suggested that
      the effects of the fungal extract on the mouse offspring may be mediated via
      maternal effects. The contribution of fumonisin B1 (FB1), a major toxic
      metabolite of F. moniliforme, in the induction of these effects was evaluated in
      this study by administering 0 to 100 mg pure FB1/kg of body weight on gestational
      days (GD) 7 through 15 to pregnant Charles River CD1 mice and assessing maternal
      health and fetal development till the end of gestation. Doses of 25 mg/kg or
      higher of pure FB1 induced maternal liver lesions (mostly necrotic changes),
      associated with ascites and increased hepatocytic nuclear diameter. Fumonisin
      doses of 50 mg/kg or higher also resulted in significantly increased maternal ALT
      on GD12, and reduced offspring bodyweights on GD18. Increased resorptions and
      decreased numbers of live offspring were only evident at 100 mg FB1/kg body
      weight. Offspring exhibited dose-dependent increase in the incidence and severity
      of hydrocephalus of both the lateral and third ventricles at doses of 25 mg/kg or
      higher. Doses of 25 mg/kg or higher also increased the sphinganine/sphingosine
      (Sa/So) ratios in maternal but not fetal livers. These results suggest that FB1
      may be a developmental toxicant accounting for most but not all earlier reported
      effects of F. moniliforme culture extract. Association of FB1 effects on the
      offspring with maternal hepatoxicity and with alteration of Sa/So ratio in
      maternal but not fetal liver supported the earlier claim that FB1 effects on the
      mouse offspring are mediated by maternal hepatotoxicity.

PMID- 8981782
TI  - Natural occurrence of gliotoxin in turkeys infected with Aspergillus fumigatus,
      Fresenius.
AB  - Thirteen samples of infected turkey lung tissue from cases of 'airsacculitis'
      were collected either at the processing plant or from a local turkey farm and
      subjected to cultural and gliotoxin analysis. Aspergillus fumigatus was isolated
      from 6 of the 13 samples; all isolates were determined to be gliotoxin producers
      when grown in laboratory culture and assayed by HPLC procedures. Gliotoxin was
      isolated from 5 of the 13 tissue but was not isolated from all tissues that were
      infected with A. fumigatus. Gliotoxin was isolated from which no A. fumigatus was
      isolated and it was not detected in three tissues from which gliotoxin-producing
      isolates of A. fumigatus were obtained. The ability of this pathogenic fungs to
      produce this immunomodulating compound in naturally infected turkeys provides
      further evidence that gliotoxin may be involved in the pathogenesis of the
      disease, aspergillosis of turkeys.

PMID- 8981783
TI  - Immunochemical detection of ochratoxin A in black Aspergillus strains.
AB  - One hundred and fifty-seven strains belonging to Aspergillus section Nigri were
      tested for ochratoxin A production using three different methods: a relatively
      new immunochemical method based on an enzyme-linked immunosorbent assay (ELISA),
      thin-layer chromatography (TLC) and high-performance liquid chromatography
      (HPLC). The monoclonal antibody-based ELISA technique was successfully used to
      screen for low levels of ochratoxin A in the black Aspergilli without
      concentrating the culture filtrates. The results were confirmed by TLC and HPLC
      analysis and chemical derivatization. These latter methods required concentrated
      filtrates. Ochratoxin A was detected in the culture filtrates of five of the 12
      A. carbonarius strains, none of the 45 A. japonicus strains and three of the 100
      isolates in the A. niger aggregate (A. foetidus, A. awamori and A. niger.

PMID- 8981785
TI  - The case against an emergency medicine residency in Kansas.

PMID- 8981784
TI  - New CDC guidelines for HIV testing.

PMID- 8981787
TI  - Information technologies in healthcare.

PMID- 8981786
TI  - A general practitioner in turn-of-the-century Kansas: W.A. Carr, M.D. (1877
      1975).

PMID- 8981789
TI  - Hemophilia and AIDS in Kansas.

PMID- 8981788
TI  - Primary care specialty choices of University of Kansas medical students, 1982
      1991.

PMID- 8981790
TI  - Does iron cause atherosclerosis?

PMID- 8981791
TI  - Gastric duplication cysts.

PMID- 8981792
TI  - Malnutrition in the elderly.
AB  - Several factors place older patients at risk for malnutrition, including
      physiologic effects of aging, chronic medical disease, psychiatric disease,
      various psychosocial problems, and effects of medication. Many of these factors
      are reversible but require early recognition and assessment. Cholesterol and
      albumin measurements may help confirm a diagnosis of malnutrition, but the most
      important indicator is weight loss. The primary interventions for nutritional
      compromise are increasing caloric, protein, and fluid intakes. Nutritional
      supplements may need to be prescribed for repletion and maintenance. Other
      nutrition-promoting interventions include exercise, avoiding constipation, and
      dental care.

PMID- 8981793
TI  - [Chorionic villus sampling in multiple pregnancies].
AB  - Prenatal genetic diagnosis is recommended in multiple pregnancies because of the
      increased prevalence of genetic abnormalities in such fetuses. It can be done
      early by chorionic villus sampling or later by amniocentesis. Several studies
      have demonstrated the efficacy and safety of chorionic villus sampling in
      multiple pregnancies. Our study describes the results of this method in a twin
      pregnancy and in 3 triplet pregnancies, which represent 3% of the chorionic
      villus samplings performed in our ultrasound unit during 1989-95. All genetically
      deformed fetuses in these pregnancies were identified by chorionic villus
      sampling and the method was not associated with fetal loss. Our results confirm
      the safety and efficacy of chorionic villus sampling as expressed in the world
      literature.

PMID- 8981794
TI  - [Anterior vaginal wall and pelvic floor sling for stress incontinence].
AB  - There is considerable doubt as to whether the intra-abdominal position of the
      urethra is the critical factor in maintenance of continence. Recent studies have
      suggested that a firm, supportive, suburethral layer is required for urethral
      closure during effort. The surgical procedure we describe is performed by vaginal
      approach and involves creation of a sling from the vaginal wall and underlying
      musculofascial layer, that provides compression and support for the urethra and
      resuspends the bladder neck. 20 women (37-70 years, mean 48.4) with severe stress
      incontinence (average of 5 wet pads per day) underwent the sling procedure
      between October 1994 and July 1995. 10/20 had had previous pelvic surgery (6 anti
      incontinence procedures and 4 hysterectomies). 3/20 had intrinsic sphincter
      dysfunction and the rest a hypermobile urethra. The surgical technique was easily
      performed. Postoperative complications were minimal, and included blood
      transfusion in 3 and in 5 suprapubic pain which subsided spontaneously or after
      oral diclofenac. The cystostomy was closed after 10.5 days (range 3-49) when
      voiding resumed and urine residual became less than 60 ml. The median follow-up
      was 9.4 months (range 3-12). All patients were cured and satisfied. 2/20 reported
      onset of urge incontinence which was found urodynamically to be de-novo detrusor
      instability due to urethral obstruction. On the other hand, all 3 patients with
      associated urge incontinence reported its disappearance postoperatively. These
      results are encouraging and this surgical procedure seems to provide a good
      solution for all types and grades of stress incontinence. Long-term follow-up is
      required to determine persistence of the good results.

PMID- 8981795
TI  - [Thoracoscopic upper thoracic sympathectomy for primary palmar hyperhidrosis].
AB  - We report our initial experience, over the past 3 years, with thoracoscopic
      sympathectomy for severe, primary, palmar hyperhidrosis in children and
      adolescents. From 1992-1995, 179 thoracoscopic sympathectomies were performed in
      61 girls and 35 boys, 5.5 to 18 years old (mean 14.8). During the first 2 years
      the procedures were performed bilaterally but not simultaneously. During the past
      years, 65 underwent bilateral, simultaneous sympathectomy, using a single 10 mm
      subaxillary port of entry. 94 (98%) had immediate and permanent relief of palmar
      sweating. The immediate postoperative course was uneventful in all except 2 who
      had residual pneumothorax that required 24-hour intercostal drainage. These
      results compare favorably with the open method and are actually better in terms
      of less pain, early discharge, quicker return to normal activity and a smaller
      and less conspicuous scar. We emphasize the benefits of early surgery in children
      with severe, palmer hyperhidrosis, to avoid the many years of psychological,
      social and physical discomfort during adolescent growth and development.

PMID- 8981796
TI  - [Post-shock optic neuropathy].
AB  - A case of rare, post-shock optic neuropathy is presented. In most cases, it
      occurs after blood loss or decrease in blood pressure. We present a woman, aged
      47, with this condition in whom 3 possible causes, hypoxia, hypercoagulability
      and vasodilatation, coexisted. Neurologists and ophthalmologists should be aware
      of this rare condition, because prompt treatment with steroids and hemodynamic
      stabilization may significantly improve outcome.

PMID- 8981797
TI  - [Fracture of the humerus after hemiarthroplasty of the shoulder].
AB  - Fracture of the humeral shaft as a complication of total shoulder replacement or
      shoulder hemiarthroplasty is infrequent, but has serious consequences. Traumatic
      injury is the most common reason for humeral fracture. The prosthesis causes
      corticolysis as a result of aseptic and septic loosening. Concomitant with
      increasing use of total and hemiarthroplasty of the shoulder, is an increase in
      aseptic loosening of the prosthesis. This increases the frequency of humeral
      fracture after the procedures. We reviewed the results of 3 patients, women aged
      54 and 68 years, respectively, and a man of 65, who were treated for humeral
      fracture as a complication of hemiarthroplasty of the shoulder. We recommend
      surgical treatment for fracture around the tip of the prosthesis. Humeral
      fracture below the tip of the prosthesis should be treated individually,
      depending on the surgeon's experience.

PMID- 8981798
TI  - [External humeral fixation in war injuries].
AB  - Type III open fractures of the humerus caused by high energy missiles or shrapnel
      in 26 male soldiers were treated by external fixation. 12 suffered from
      associated injuries involving the head and chest, 12 had 14 nerve injuries, and 4
      required simultaneous repair of the brachial artery. Results in 19 examined after
      an average of 6.5 years were excellent in 22%, good in 52%, fair in 16%, and poor
      in 10%. The aim of external fixation is functional limb salvage. We think high
      energy gunshot fractures should be classified as III-d because of the severe
      damage to the soft tissue, which differs from that of low-velocity, gunshot
      fractures or farm injuries. We conclude that external fixation is the preferred
      form of primary stabilization of severe open fractures of the humerus. It has
      reduced the incidence of chronic infection and has improved the prognosis of
      vascular repairs. The treatment of the soft tissues, skin coverage, and
      ultimately reconstructive surgery are facilitated. Early limb function allows for
      a better final result. For delayed union and pin-tract infection a different
      definitive method, such as internal fixation or a plaster case, is required.

PMID- 8981799
TI  - [Juvenile myoclonic epilepsy--an underdiagnosed epileptic syndrome].
AB  - Clinical and electroencephalographic data and response to drug therapy of 3 boys
      and 3 girls aged 14-19 years, mean 16, with juvenile myoclonic epilepsy (JME) are
      described. All presented with violent myoclonic jerks upon awakening, prompted by
      sleep deprivation and precipitated by deliberate awakening. Following onset of
      myoclonic jerks, generalized tonic-clonic seizures (GCTS) and absences occurred
      after 6-18 months (mean 11). The EEG revealed normal background activity in all,
      along with generalized epileptiform activity in the form of 3-4 Hz polyspike/slow
      wave or spike/slow wave, commonly induced by hyperventilation. Valproic acid
      (VPA), 12 mg/kg/day (range 10-15), resulted in complete and rapid cessation of
      myoclonic jerks, of absences and recurrent GTCS. Discontinuation of VPA resulted
      in recurrence of myoclonic jerks and then GTCS, but were completely controlled by
      reinstitution of VPA. All have remained asymptomatic on VPA, with cognition
      preserved, during a follow-up of up to 6 years. JME is a unique, benign,
      epileptic syndrome easily and rapidly controlled by rather small doses of
      valproic acid given on a long-term basis. Myoclonic jerks may serve as a reliable
      indicator of JME and therefore should be screened for in any case of unprovoked
      generalized seizures. The smallness of the doses of the drug used suggests that
      the dose prescribed should be "syndrome" related rather than weight related, as
      is usually prescribed in children.

PMID- 8981800
TI  - [Spontaneous pneumomediastinum in a child].
AB  - Spontaneous pneumomediastinum results from nontraumatic, mediastinal air leakage,
      without underlying lung disease. It is an uncommon, but important condition found
      in healthy young adults and children presenting with chest pain and shortness of
      breath. It should be considered in the differential diagnosis of chest pain. We
      present a 12-year-old boy who complained of chest pain and was found to have a
      spontaneous pneumomediastinum. We suggest that spontaneous pneumomediastinum is
      underdiagnosed in children.

PMID- 8981801
TI  - [Cellular immune responses in rheumatic fever].

PMID- 8981802
TI  - [Stereotactic pallidotomy--effective surgery for Parkinson's disease].

PMID- 8981803
TI  - [Testicular varicocele in adolescence--a complicated and unsolved enigma].

PMID- 8981805
TI  - [The shaken baby syndrome].

PMID- 8981804
TI  - [Creatine kinase MM and MB isoforms and their potential in the diagnosis of acute
      myocardial infarction].

PMID- 8981806
TI  - [Female sexual abuse of children].

PMID- 8981807
TI  - [Fish oil as prevention and treatment for hypertension--to be recommended and to
      whom?].

PMID- 8981808
TI  - [The holy cows of pregnancy and puerperium mental syndrome].

PMID- 8981809
TI  - [Clinical use of human chorionic gonadotropin in the treatment of trophoblastic
      neoplasia].

PMID- 8981810
TI  - [Gastro-esophageal reflux, sleep apnea syndrome, and their association].

PMID- 8981811
TI  - [Epidemiology of AIDS--discrimination, ethics and social policy].

PMID- 8981812
TI  - [Severe fatal shock after syncope in an old man].

PMID- 8981813
TI  - [Cranial base surgery].
AB  - A review of 172 consecutive patients who underwent surgery for cranial base
      tumors was undertaken to determine efficacy and complication rate. 95% of the
      tumors were benign or of low grade malignancy; 24% were greater than 4.5 cm in
      diameter and 34% were 3-4.5 cm; 32 were petro/clival and 17 cavernous sinus
      tumors. Radical tumor resection was attained in 60% and subtotal (> 90% of
      volume) in 35%. The mean preoperative Karnofsky functional score was 72, which
      postoperatively had improved significantly to 83.5 patients (2.9%) died
      perioperatively, and later an additional 3 died of their disease; 3/5 died
      following reoperation at other hospitals. 3 (1.7%) had major, prolonged
      deterioration following surgery. This series presents experience with, and
      demonstrates overall high quality outcome, in patients with cranial base tumors
      at a center with special interest in and facilities for cranial base surgery.

PMID- 8981814
TI  - [Occupation and bladder cancer].
AB  - The proportion of all cancers attributed to occupational environment has been
      estimated at only 4% (range 2-8%), although 20% of bladder carcinoma is
      occupationally related. In Israel, 7 substances have been established as bladder
      carcinogens and another 2 are suspected. The linkage between bladder cancer and
      occupation was examined according to occupational history and work-place
      exposure; smoking habits were also noted. The study population consisted of 1230
      patients diagnosed as suffering from bladder cancer in 1988-1993 in 5 central
      hospitals; 80% were men, mean age 68.9 +/- 10.8 years. Only 41% of the files
      (mean 45%, range 13-69%) had information about last job, but no information on
      exposure. The information in 226 files out of 500 (45%) about previous
      occupations indicated potential association with bladder cancer in 68%. These
      occupational fields were: medicine (doctors, nurses), building and agriculture,
      and comprised 27.6% of all jobs reported. Other occupations connected with
      bladder cancer reported with lesser frequency were in the paint, rubber, textile
      and leather industries. There was information about smoking, a known carcinogen
      for bladder cancer, in only 59% of the files. Our findings indicate that the
      overall situation in Israel is similar to that in other countries. There is a
      connection between bladder cancer and exposure to carcinogens at work, but the
      medical files were not a good source of information regarding the precise extent
      of this problem. Recording occupational history is important for proper medical
      surveillance of high risk populations, for early detection of bladder cancer, and
      for prevention of further exposure.

PMID- 8981816
TI  - [Follow-up of intrauterine contraceptive devices].
AB  - The intrauterine contraceptive device (IUCD) is the most popular, reversible
      contraceptive method, worldwide. Leaving an IUCD in-utero even beyond the time
      recommended by the manufacturer has been found both safe, and effective in terms
      of contraceptive ability. In 1995 we screened the medical records of the
      gynecologic infirmaries of 4 agricultural settlements (kibbutzim) and found 78
      women who had worn an IUCD continuously for more than 5 years. All had been
      regularly examined every 6 months. Most of the IUCDs (63, 80.7%) were copper
      containing. Mean IUCD wear was 7.9+/- 2.6 years (range, 5-17 years). At the time
      of the study, 38 (48.7%) of the IUCDs were still in utero. Related complications
      were 3 cases of dysmenorrhea (3.8%) and 20 of metrorrhagia. No pregnancies or
      pelvic infections were recorded. This study also shows that wearing an IUCD
      beyond the time recommended by the manufacturer is not associated with loss of
      contraceptive effectiveness. Furthermore, the rate of IUCD-related complications
      after 5 years of wear was not higher than during the first 5 years. To support
      these findings further studies with larger samples are needed.

PMID- 8981815
TI  - [Primary brain tumors].
AB  - In our retrospective analysis of 305 patients with primary brain tumors, treated
      and followed at Rambam Medical Center between 1983-1990, 56% were males; mean age
      was 43; 47% were Ashkenazi Jews, 22% Sephardi Jews, 22% Arabs and 9% were Jews of
      unspecified origin. 3-year actuarial survival for all patients was 33.5%, Arabs
      51%, Sephardi Jews 40%, Ashkenazi Jews 20%; for those younger than 20, it was
      57%, and older than 20, 26%. Diagnoses were: astrocytoma grades I-II, 68%;
      astrocytoma grade III, 24%; glioblastoma multiforme, 5.5%; medulloblastoma 73%;
      ependymoma, 75%; oligodendroglioma, 85%; meningioma, 100%; pituitary adenoma,
      100%. Survival probability of those with glioblastoma multiforme treated by
      combined surgery and radiotherapy was superior to that of those treated by
      surgery alone. In low-grade astrocytoma there was no difference in survival
      probability between those with combined therapy and those treated by surgery
      alone. Survival when the diagnosis was based on imaging studies alone without
      histological confirmation of malignancy, was similar to that of those with
      glioblastoma: only 3.0% at 3 years. Prognostic factors identified by univariate
      analysis were histology, age of patient and ethnic origin, and type of treatment.

PMID- 8981817
TI  - [Geriatric consultations in a general hospital].
AB  - The increasing numbers of the elderly admitted to general hospitals, and the
      complexity of their problems, has increased the need for geriatric consultations.
      We evaluated geriatric consultations given at the Wolfson Medical Center by the
      geriatricians of Shmuel Harofeh Hospital. Data on 6-months of consultations in
      medical, surgical, urologic, neurologic, orthopedic and intensive care
      departments were evaluated. 7,910 elderly (65 years and over) were admitted
      during this period, representing 58% of all admissions; 742 (9.4%) were targeted
      for geriatric consultation. The largest number of consultations (525) were in the
      medical wards, but the highest rate of consultations was in the orthopedic ward
      for rehabilitation after operations for hip fractures. The selection of patients
      for geriatric consultation at Wolfson Hospital was done by the staff of each
      ward. This method differs from that in most general hospitals abroad, where
      selection is by geriatric teams. Despite this difference, our data show that the
      rates of consultations were similar. Also, the multidisciplinary teams consisted
      of members of the staff of each ward and the geriatric consultant. The method of
      geriatric consultations presented is easy to set up, simple to operate, efficient
      and appreciated by the medical staff of the departments.

PMID- 8981818
TI  - [Pseudotumor cerebri during pregnancy].
AB  - Pseudotumor cerebri (PTC) is a syndrome characterized by intracranial
      hypertension and associated with headaches, visual disturbances and papilledema,
      but without any identifiable intracranial pathology. PTC during pregnancy is
      uncommon; we report 2 such cases. Neither patient had specific complications
      associated with PTC. In 1 case, US of the optic nerve was used in the management.
      Both delivered vaginally and each had a normal puerperium. We conclude that PTC
      during pregnancy has no adverse effect on outcome.

PMID- 8981819
TI  - [Psoas abscess: diagnostic dilemma in childhood].
AB  - A series of 16 children diagnosed as having a psoas abscess or deep iliac
      lymphadenitis seen over a 25-year period (1970-1994) is presented. 10 were
      treated conservatively while 5 were drained surgically and 1 percutaneously under
      imaging guidance. The presenting signs and symptoms may mimic the frequently seen
      entities, acute appendicitis and acute hip arthritis. Lower abdominal and
      inguinal pain, limp, fever and increased white count are common in all of these
      conditions. Accurate differential diagnosis is necessary to avoid unnecessary
      surgery due to a wrong diagnosis. Ultrasonography is preferred for diagnosis.
      Antibiotic therapy should be instituted immediately, aimed primarily at
      Staphylococcus aureus, the most common causative agent, although other organisms
      may be implicated. When a psoas abscess has been diagnosed, surgery and drainage
      are indicated. One of the preferred approaches is percutaneous drainage under
      imaging guidance. Convalescence is usually rapid and without late sequelae.

PMID- 8981820
TI  - [Treatment of Helicobacter pylori positive ulcer--the search for simple and
      effective therapy].

PMID- 8981821
TI  - [Inherited breast cancer].

PMID- 8981823
TI  - [Bone grafts in orthopedic surgery].

PMID- 8981822
TI  - [Brain MRI in multiple sclerosis].

PMID- 8981824
TI  - [Treatment and follow-up by primary care physicians of patients after coronary
      bypass surgery].

PMID- 8981825
TI  - [Anesthesia and postoperative management management of patients with Duchenne's
      dystrophy].

PMID- 8981826
TI  - [Nephron sparing surgery for renal cell carcinoma].

PMID- 8981827
TI  - [Tuberculosis in Palestine].

PMID- 8981828
TI  - [Aspect of patho-receptor in the modern pharmacology for drug design developing
      from Japanese traditional sino-medicines systems].
AB  - This article is a summary of the molecular patho-pharmacological studies
      continuously investigated for more than 30 years in Toyama Medical &
      Pharmaceutical University. The aim of this study was to develop the motivation
      and the strategy for the original drug-design by targeting the pharmacological
      mechanism of receptor modified by the pathological state in the animal models for
      the diseases, followed by searching the pathoreceptor-sensitive drugs as a probe
      of new medicines. The drug activity consists of two factors, affinity and
      intrinsic activity to the receptor, depend on their chemical structures of
      supporting moiety and radical moiety, respectively. The former can be discovered
      from the natural products, composing Japanese traditional Sino-medicines, and the
      later can be modified by chemical synthesis. By using this strategy, several new
      findings, a large number of new compounds and/or new pharmacological activity,
      were obtained as follows: I. On the molecular pharmacology of nicotinic ACh
      receptor. II. On the development of new drugs affecting on smooth muscle. III. On
      the pathopharmacological investigation with a model of diabetic mice. IV. On the
      applied pharmacology of Japanese traditional Sino-medicines.

PMID- 8981829
TI  - [Chemical constituents of original plants of Cimicifugae rhizoma in Chinese
      medicine].
AB  - Cimicifugae Rhizoma have been used as an anti-inflammatory, analgesic and
      antipyretic remedy in the traditional Chinese medicines. Many 9,19-cyclolanostane
      glycosides have been isolated from Cimicifuga and related genera. Two
      biogenetically key compounds, acetylshengmanol xyloside and cimicifugoside H-1,
      were isolated and their chemical structures were elucidated by our group. The
      former compound seems to be the parent component of the other glycosides such as
      cimigenol xyloside from C. dahurica, C. iaponica and C. acerina. The latter
      glycoside, cimicifugoside H-1 was isolated together with cimicifugosides H-2-H-6
      from commercial Cimicifugae Rhizoma. They are novel glycosides having a hydroxyl
      group ay C-11, and cimicifugosides H-3, H-4 and H-6 were trinor-triterpenol
      glycosides. Cimicifugoside H-1 changed into H-2, H-3 and H-4 under acidic or
      alkaline conditions. In this review, the structure elucidation of the above
      glycosides and their chemical transformation into other Cimicifuga glycosides are
      described.

PMID- 8981830
TI  - [Physicochemical properties of suplatast tosilate racemate and enantiomers].
AB  - The physicochemical properties of the enantiomer and racemates of suplatast
      tosilate (ST) were investigated by means of infrared spectroscopy, solid-state
      13C CP/MAS NMR spectroscopy, thermal analysis, and X-ray diffraction analysis,
      and by measuring the solubility and hygroscopy. The infrared and NMR spectra and
      X-ray diffraction pattern of the enantiomer were distinctly different from those
      of the racemate. The melting point of the enantiomer was lower than that of the
      racemate by 5 degrees C, while the solubility of the enantiomer was 1.3 times
      higher than that of the racemate. The hygroscopic rate of the enantiomer was
      greater than that of the racemate. These results suggested that ST was classified
      into a racemic compound crystal. Furthermore, by comparing the relative peak
      intensity ratios on X-ray diffraction patterns of the crystals with various
      optical purities prepared by recrystallization, it was found that a mixture of
      racemic compound crystals and either of racemic mixture crystals or racemic solid
      solutions was obtained by recrystallization of ST in the content of 0 to 64%ee,
      while the recrystallization of ST in the content of more than 64%ee led to the
      formation of racemic mixture crystals or racemic solid solutions.

PMID- 8981831
TI  - [Bayesian forecasting of plasma vancomycin concentration using time-dependent
      pharmacokinetics].
AB  - A new prediction method of vancomycin (VCM) pharmacokinetics has been developed
      using the modified Bayesian forecasting method involved in time-dependent
      pharmacokinetics in clearance. We investigated to evaluate the usefulness of this
      new prediction method compared with that of the ordinary Bayesian forecasting
      method. Serum samples, obtained from 4 patients at least 3 different days during
      the period for the VCM treatment were assayed by fluorescence polarization
      immunoassay. VCM pharmacokinetic parameters and predicted serum VCM
      concentrations were calculated using this new method and the ordinary one
      according to the one-compartment model. The precision of the predicted serum VCM
      concentrations by these two methods at the third experimental day were evaluated
      with the mean prediction error (ME), mean absolute prediction error (MAE) and
      root mean squared error (RMSE). The most precise and least-bias prediction of
      serum VCM concentrations were observed using this new prediction method (ME: 
      0.36 +/- 1.40, MAE: 1.13 +/- 0.82 and RSME: 1.37). The time-dependent decrease of
      VCM clearance was observed in all patients. Therefore, the fitting of the actual
      serum VCM concentrations obtained using the ordinary method produced less precise
      results than that using this new method. These results suggest the usefulness of
      this new prediction method considering time-dependent changes in VCM clearance.

PMID- 8981832
TI  - [Pharmacological profiles of a novel tachykinin NK-2 receptor antagonist, TAC
      363].
AB  - We examined the pharmacological profiles of a novel tachykinin NK-2 receptor
      antagonist, Na-(tert-butylcarbamoyl)-L-glutaminyl-L-tryptophyl-alpha-azap++ +
      henylalanine 2-benzyloxyethylamide (TAC-363). In vitro studies showed that TAC
      363 caused a rightward shift of the contraction response curve with a slight
      inhibition of maximal response for the neurokinin A (NKA)-induced contraction of
      the hamster trachea and parallel rightward shift of the curve for the substance P
      (SP)-induced contraction of the guinea-pig ileum. The pA2 values were 9.82 and
      8.42 on the contraction by NKA and SP, respectively. The selectivity of TAC-363
      to NK-2 receptor was 25 times higher than that to NK-1 receptor. The compound did
      not affect the histamine and acetylcholine-induced bronchoconstriction in guinea
      pig ileum. Intravenous administration (0.1-1 mg/kg) of the compound inhibited
      dose-dependently both NKA- and capsaicin-induced bronchoconstriction in guinea
      pigs. The inhibitory effect of the compound lasted up to 60 min on NKA-induced
      bronchoconstriction in guinea-pigs. These results suggest that TAC-363 is a
      potent and selective NK-2 receptor antagonist, which is effective in vitro and in
      vivo. It may be useful in the treatment of NKA-dependent pathology, especially
      bronchial asthma.

PMID- 8981833
TI  - [Effect of formation of surface complex between hydroxypropylcellulose and sodium
      dodecylsulfate on dispersion/flocculation of O/W-type emulsion of soybean oil].
AB  - An O/W-type emulsion of soybean oil (theta v = 0.05) was prepared in the presence
      of various concentrations of hydroxypropylcellulose (HPC) and sodium
      dodecylsulfate (SDS). The mean diameter (d) of secondary particles of the oil
      droplets decreased with concentrations of SDS and HPC after attaining a maximum
      at [SDS] = 5 mmol/dm3 and [HPC] = 10(-3) g/dl, while the relative viscosity (eta
      rel) of the emulsion increased with an SDS concentration after attaining a
      minimum around 5 mmol/dl3 when the HPC concentration was kept constant. These
      facts were explained in terms of the formulation of a surface complex by
      hydrophobic interaction between SDS and HPC adsorbed on the surface of the
      droplets. When the concentration of SDS is low, it bridges between the HPC
      segments intra- and intermolecularly on and between the particles, resulting in
      shrinking of the HPC surface layers as well as in bridging among the particles.
      Therefore, the total volume of the secondary particles effective on eta rel
      decreases while the d-value increases with the SDS concentration. When the
      concentration becomes high, binding ratio of SDS to HPC also increases and the
      segments are repulsive each other owing to the negative charges given by the
      bound SDS. As a result, the adsorption layer swells and the secondary particles
      are redispersed. This fact causes an increase in eta rel and a decrease in d
      value with a concentration of added SDS.

PMID- 8981834
TI  - Cardiac glycosides.

PMID- 8981835
TI  - As others see us.

PMID- 8981836
TI  - Paediatric calls to an inner city accident and emergency department: service
      demand and advice given.
AB  - Patients routinely call both Accident and Emergency (A & E) departments and
      General Practice for advice. Many of these calls concern children. In the UK,
      telephone calls for advise made to A & E departments are usually dealt with by
      nursing staff in an informal manner. This paper focuses on telephone calls
      concerning children received in a busy inner city department. Data were collected
      using a Telephone Consultation Record proforma (TCR) developed to document all
      calls to the A & E department. There were a total of 597 calls to the A & E
      department documented during the study period of which 218 (37%) concerned
      paediatric patients. The majority of calls were concerning children under the age
      of 5. One-third of callers were given self-care advice. This paper reports on the
      volume of calls, the nature of patients' problems and the outcome in terms of the
      advice given to the caller. The implications of the findings are discussed. Given
      the current demand for telephone advice, A & E departments should examine the
      nature and demand for telephone advice and explore methods of providing training
      and support to staff carrying out this role.

PMID- 8981837
TI  - The laryngeal mask: an essential part of emergency airway management.
AB  - In this article I have endeavoured to introduce the laryngeal mask airway to
      those who have not come in contact with it in their clinical experience. Those
      who have and want to know more will, after reading it, form a knowledge base
      which, I hope, will encourage the acquisition of the skill of insertion. The
      background and development of the mask are described along with a description of
      the mask's insertion into the airway and its positioning. I have also included
      our experience gained whilst introducing the mask into our Hospital Trust, the
      Royal Berkshire & Battle Hospital NHS Trust (UK), and the training programme
      which we set up to train an retrain necessary personnel. The aim of the article
      is not to usurp the endotracheal tube's position in emergency airway management,
      but to enlighten the reader as to how the mask can dovetail in with its use. The
      endotracheal tube, of course, remains the gold standard in the isolation of the
      adult patient's airway in cardiopulmonary arrest.

PMID- 8981838
TI  - Accuracy and efficiency of X-ray requests initiated by triage nurses in an
      accident and emergency department.
AB  - A study was carried out from 1 March 1995 to 31 March 1995 in the Accident &
      Emergency department, Pamela Youde Nethersole Eastern Hospital, Hong Kong. The
      aim was to assess the feasibility of requesting X-rays by triage nurses based on
      a pre-set protocol prior to patients being seen by a doctor. Judgement of the
      attending physician was used as the gold standard by which to judge the need for
      radiographs requested by the triage nurse. In addition, the senior medical
      officer or consultant would judge whether the triage nurse had applied the
      protocol correctly. A total of 934 patients were included in the study and 883
      (94.54%) patients had X-rays requested by the triage nurse. Only 5.44% of the
      radiographs requested by nurses were considered to haven been unnecessary by the
      doctor. There was no statistically significant difference in agreement for the
      child and adult groups. In 917 (98%) of cases, nurses had adhered to the
      protocol. A saving of an average of 18.59 minutes of total service time was
      obtained during the study. Requesting of X-ray by triage nurse was feasible

PMID- 8981839
TI  - Nursing management in the accident and emergency department of women undergoing a
      miscarriage.
AB  - Women experiencing a miscarriage are a regular daily occurrence in some Accident
      and Emergency (A & E) departments. Each woman's miscarriage experience is unique
      and individual and women deserve an individual response to their problems, one
      that is built on trust and communication. Therefore, emergency nurses must
      appreciate that each woman is an individual and must explore the history she
      brings to the current event, the meaning she attributes to the miscarriage, and
      its impact on her life. These women need to be cared for in an environment that
      not only allows privacy but also respect and dignity. Nurses need to be able to
      communicate effectively, to give good physical care and be willing to take on the
      emotional significance that miscarriage can have. This paper aims to explore the
      needs of the woman experiencing a miscarriage. It attempts to look at what
      emergency nurses can do to meet those needs, and what can be done to make this
      difficult time as tolerable as possible for the woman or couple, when they
      present to the A & E department.

PMID- 8981840
TI  - The battered woman in the accident and emergency department.
AB  - In today's society one of the most pressing health care problems is family
      violence. This article focuses on female abuse and how critical care nurses need
      to gain awareness of their attitudes about battered women, educate themselves
      about the dynamics of battering and obtain the knowledge and skills needed for
      effective assessment and nursing intervention.

PMID- 8981841
TI  - The tympanic membrane thermometer in paediatrics: a review of the literature.
AB  - This literature review looks at published works on the accuracy, reliability and
      sensitivity of the tympanic membrane thermometer in the paediatric population,
      particularly in relation to those who present in the Accident and Emergency
      department. Decisions that influence patient care outcomes are often based on
      information obtained from taking the child's temperature. Numerous studies have
      been conducted to examine temperature sites and instruments used. The most recent
      temperature measuring device to be used by nurses in assessing their patients is
      the tympanic membrane thermometer. The advantages of tympanic membrane
      temperature measurement include ease of use, rapid results and convenience for
      both nurse and child. However, inconsistent study reports have revealed some
      concerns about the use of the tympanic membrane thermometer as a routine
      measurement tool of body temperature in children. To meet the goal of accurate
      assessment of body temperature the practitioner must understand the principles
      behind the use of the tympanic membrane thermometer and thus use it
      appropriately.

PMID- 8981842
TI  - Working for Medecins sans Frontieres.
AB  - Medecins sans Frontieres (MSF), the world's largest independent organization for
      emergency medical relief, needs nurses willing to volunteer their skills and
      their time to work in the field. Trevor Lines, RGN, a veteran of five MSF
      missions, explains what the work involves, why he does it and what you need to do
      if you want to apply.

PMID- 8981843
TI  - Physiotherapy in an accident and emergency department.
AB  - This paper examines the role of a full-time physiotherapist in a busy Accident
      and Emergency department. It describes the service offered and concludes with an
      example of the management of a patient with an RTA related neck sprain.

PMID- 8981844
TI  - Dilemma: three patients were brought into Accident and Emergency from a road
      traffic accident.

PMID- 8981845
TI  - Are we giving away nursing?

PMID- 8981846
TI  - Concepts related to Chinese patients' perceptions of health, illness and person:
      issues of conceptual clarity.
AB  - Since most health professionals who care for Chinese patients are trained using
      Western medical educational systems, they are often unaware of the complex
      Chinese culture that influences their patients' responses to care. Discrepancies
      often exist between health professionals' and Chinese patients' perceptions of
      health and evaluations of the quality of care. In order to provide culturally
      sensitive care for this population, the complex Chinese traditional philosophies,
      such as the theory of yin and yang and the five phases, as well as the
      philosophies related to the concept of personhood including Confucianism, Taoism
      and Buddhism are examined first. This is because these theories and philosophies
      not only influence Chinese patients' values and beliefs, but also determine their
      perceptions of health, illness and nursing care. The discussion of implications
      for surgical cardiovascular nursing practice for this particular population are
      followed.

PMID- 8981847
TI  - Developments in nursing in accident and emergency services: providing nursing
      advice to the Scottish Office Department of Health.

PMID- 8981848
TI  - New ventilatory strategies in acute respiratory failure.
AB  - New management options for acute respiratory failure aim at avoiding ventilator
      induced lung injury while maintaining adequate gas exchange. Selected approaches
      examined in this article include methods to augment carbon dioxide elimination
      with tracheal gas insufflation, venovenous extracorporeal carbon dioxide removal,
      and intravascular oxygenation. Improving oxygenation can be accomplished by
      judicious use of positive end-expiratory pressure, venoarterial extracorporeal
      membrane oxygenation, and pharmacologic intervention with inhaled nitric oxide.

PMID- 8981849
TI  - Pressure controlled-inverse ratio ventilation.
AB  - One of the many challenges in the management of the patient with adult
      respiratory distress syndrome is optimal application of mechanical ventilation.
      Pressure controlled-inverse ratio ventilation has surfaced as a possible
      alternative to conventional ventilation for patients affected by this condition.
      In pressure controlled-inverse ratio ventilation, the conventional inspiratory-to
      expiratory ratio is reversed, allowing the inspiratory phase to lengthen with an
      accompanying increase in mean airway pressure. When carefully applied, mean
      airway pressure adjustments can be manipulated without increases in positive end
      expiratory pressure and peak airway pressure, thus minimizing the risk of
      alveolar rupture and worsening of lung injury.

PMID- 8981850
TI  - Terminal weaning from mechanical ventilation: planning and process.
AB  - There are two major goals of critical care: (1) to save those with a chance to
      live and (2) to help patients who are dying have a peaceful and dignified death.
      If reversal of the disease process is not possible and the patient is
      experiencing substantial pain and suffering, goals need to be reviewed and
      potentially redefined. These new goals may be to remove unwanted or nonbeneficial
      therapy, to provide death with dignity, and to support the family. This article
      details aspects of the decision-making process regarding withdrawal of mechanical
      ventilation, including ethical principles; decision-making for autonomous
      patients and non-autonomous patients; advance directives; planning withdrawal of
      support; terminal weaning methods; patient comfort; family support; and future
      directions for research, practice, and education.

PMID- 8981851
TI  - Using drug chronotherapy to wean patients from mechanical ventilation.
AB  - Discontinuation of positive pressure mechanical ventilation results in decreased
      intrathoracic pressure. Although there has been extensive research into factors
      associated with weaning adults from mechanical ventilatory support, little
      attention has been paid to the role of left ventricular performance. Research
      also has not focused on interventions that might optimize ventricular
      performance. The purpose of this article is to explore the potential effect of
      cardiac dysfunction in weaning and the role of drug chronotherapy as a strategy
      to modify patients' responses to weaning from mechanical ventilatory support.
      Biophysical principles involved are reviewed, and the development of a
      chronotherapeutic intervention is described. Two case examples illustrate the use
      of drug chronotherapy during the weaning process.

PMID- 8981852
TI  - Respiratory care of the postoperative lung transplantation patient.
AB  - The management of patients receiving lung transplantation has been evolving
      during the last thirty years. Transplant programs have continued to develop both
      in United States and internationally. Patient evaluations and experiences with
      procedures help guide the decision as to which type of transplant would best
      benefit the patient. To care for lung transplantation patients, nurses need an
      understanding of the alterations in physiology from the procedure. An
      understanding of the clinical experiences in the areas of immunosuppression,
      preoperative conditioning, surgical techniques, preservation techniques,
      ventilatory management, and nursing care have made significant contributions to
      patient survival.

PMID- 8981853
TI  - High-altitude pulmonary edema: a clinical crisis.
AB  - High-altitude pulmonary edema is a serious clinical condition observed in
      individuals participating in mountain climbing and skiing at high altitudes. High
      altitude pulmonary edema is an oncardiogenic form of pulmonary edema. Atrial
      natriuretic factor and endothelin are implicated and ventilatory support is
      important in preventing fatalities.

PMID- 8981855
TI  - Developing practice: the contribution of the master's prepared nurse.

PMID- 8981854
TI  - Optimizing outcomes in ventilator-dependent patients: challenging critical care
      practice.
AB  - This article examines the structure and process of a collaborative practice team
      established specifically to improve the quality and financial outcomes of
      ventilator-dependent patients in a tertiary care teaching hospital. A brief
      overview of descriptors regarding ventilator-dependent patients is synthesized
      from the literature and compared with the population at St. Luke's Episcopal
      Hospital in Houston, Tex. An analysis of statistically significant physiologic
      variances that have been found to increase mechanical ventilation time or length
      of stay is detailed. Focused quality initiatives are discussed. Specific criteria
      indicative of improved outcomes are presented along with recommendations for
      future improvements.

PMID- 8981857
TI  - Introducing primary nursing: nurses' opinions.
AB  - This article reports on one aspect of a research project carried out to monitor
      and evaluate the introduction of primary nursing on four demonstration wards in
      one health authority. Nursing staff working on the wards were interviewed to
      identify how the changes were affecting them and their work. Stress
      questionnaires were also completed by a sample of nurses on the wards.
      Responsibility and communication--key concepts emerging from the data--are
      discussed and related to the literature on primary nursing.

PMID- 8981856
TI  - The evolving role of the clinical nurse specialist within the comprehensive
      breast cancer centre.
AB  - The collaborative functioning of a specialist multidisciplinary team is a
      fundamental prerequisite in the establishment of designated breast cancer units
      throughout the U.K. It is, therefore, opportune for clinical nurse specialists to
      examine carefully their unique contribution to the care of women with breast
      disease. This article explores the contemporary developments in service provision
      and identifies potential areas for nursing development. It is only when the role
      of the breast care nurse is explicitly defined can research begin to determine
      the effectiveness of nursing practice in terms of women's health.

PMID- 8981858
TI  - Readability of printed educational materials used to inform potential and actual
      ostomates.
AB  - This paper is primarily concerned with the use of readability formulas to
      determine the reading ease of printed education materials (PEMs) given to ostomy
      patients. Whilst the particular clinical focus is stoma care nursing, the content
      is relevant to all nurses who use printed text to inform their patients. PEMs
      have significant advantages in conveying information compared with verbal
      presentations alone. Methods to calculate readability using the Flesch, FOG and
      SMOG readability formulas are described. Presentation factors that affect
      readability are briefly reviewed, including use of 'white space', font size and
      paper colour. The problem of functional illiteracy and the need for indirect
      assessment of patient literacy are discussed. PEMs in use are often found to be
      difficult to read. Stress is identified as a potential factor in further reducing
      a patient's ability to deal with information. Three commercially available PEMs
      are evaluated for ease of reading and their score on the FOG index indicates that
      only about 40% of the UK population would understand them. Nurses are advised to
      evaluate the readability of their PEMs and to assess indirectly the literacy of
      their patients, so that they can more sensitively match PEMs to patient ability
      and need.

PMID- 8981859
TI  - Paediatric nursing and children's autonomy.
AB  - The topic of children's rights is a wide-ranging and complex subject, and in
      recognition of this fact this paper specifically addresses the concept of the
      right of children to make decisions about their own health-care. This paper
      explores the many factors which may influence a child's right to autonomy,
      including family relationships and the broader external influences exerted by
      health-care workers. The discussion highlights the dilemmas which may be faced by
      nurses when their values and beliefs, or hierarchical position within the health
      care structure, inhibit their ability to promote children's autonomy.

PMID- 8981860
TI  - Coping with rheumatoid arthritis. How can specialist nurses influence it and
      promote better outcomes?
AB  - Psychological stressors are said to be an important influence on the outcome of
      chronic illness such as rheumatoid arthritis (Engel, 1977). Helping patients to
      cope with stressors is identified as a central concept in the delivery of nursing
      care (Khan et al., 1994). It is thus reasonable to suggest that rheumatology
      nurses may be key players in the process of coping with rheumatoid arthritis. But
      in order for rheumatology nurses to be effective players in this process, they
      need to discourage coping behaviour(s) linked to poor outcomes, and/or promote an
      overall behaviour pattern linked to a better outcome. Literature showing the link
      between different coping behaviours and outcome is examined, and cognitive
      restructuring is emphasized as one method nurses could use. Having identified
      coping behaviour which is optimal in terms of future outcome, further study of
      different forms of coping-based educational intervention is suggested, to reveal
      how such patterns of behaviour can be taught by nurses in the most effective way.

PMID- 8981861
TI  - Residents' perspectives of their first 2 weeks in a long-term care facility.
AB  - This study investigated residents' perspectives of their first 2 weeks in a long
      term care facility (LTCF). Twelve residents were interviewed to determine their
      experiences during the first 2 weeks, their needs, priorities and expectations,
      and their views about how relocation from home could be facilitated. The constant
      comparative method of qualitative analysis (Glaser & Strauss, 1967) was used.
      Qualitative analysis of the audiotaped interviews revealed four main categories:
      emotional reactions, transition activities, reflecting on their situation, and
      connecting with a personal philosophy. Residents' responses indicated that if
      they had actively participated in the decision to be admitted, the adjustments to
      the LTCF was easier. Connecting with a personal philosophy was also a significant
      factor. Nursing implications include recognition of the importance of preparing
      residents for admission, involving them in the decision, and listening to their
      perspectives throughout the relocation experience.

PMID- 8981862
TI  - Endotracheal suctioning: an example of the problems of relevance and rigour in
      clinical research.
AB  - Endotracheal suctioning is a routine but potentially dangerous procedure. The
      literature documenting approaches to minimizing the cardiopulmonary complications
      of endotracheal suctioning is reviewed. Hyperoxygenation, hyperventilation,
      hyperinflation and the use of adaptors are all evaluated. The effects of
      endotracheal suctioning on haemodynamics and oxygen transport are also examined.
      The traditional dualist approach to the respiratory and cardiovascular systems is
      contrasted with the recent emphasis on oxygen transport by the cardiopulmonary
      system. The trade-off between the rigour of laboratory studies (which can be well
      controlled but are difficult to generalize) and the relevance of clinical
      research (which is more easily generalized but which often lacks internal
      validity) is discussed. Although research studies have become both more
      methodologically and conceptually sophisticated, definitive recommendations for a
      safe and effective suctioning procedure still remain elusive.

PMID- 8981863
TI  - The management of clinician nutrition in NHS hospitals.

PMID- 8981864
TI  - Positioning adult health nursing for the future.

PMID- 8981865
TI  - Tubes: a nurse's guide to enteral feeding devices.
AB  - Nurses use a variety of sophisticated enteral feeding devices to provide
      nutritional feedings directly into the gastrointestinal tract. Nurses must be
      familiar with all aspects of enteral nutrition support to safely provide care.
      Appropriate care includes identifying high-risk patients, observing for symptoms
      of malnutrition, administering enteral feedings safely, assessing for possible
      complications, and monitoring the effectiveness of nutritional care.

PMID- 8981866
TI  - Rehabilitating stroke patients in the acute care setting.
AB  - The 1990s has been heralded as the Decade of the Brain. The National Stroke
      Association refers to stroke as a brain attack. Medical and nursing interventions
      are aimed at limiting the extent of brain injury, promoting early reperfusion,
      and preventing complications as a result of secondary injury or hazards of
      immobility. Medical-surgical nurses play a key role in facilitating collaborative
      rehabilitation in the acute care setting to achieve expected outcomes for the
      patient and family.

PMID- 8981867
TI  - Patient and family education: an interdisciplinary process.
AB  - An interdisciplinary education and discharge plan was developed in a 404-bed
      teaching hospital to coordinate and integrate the function of patient and family
      education across disciplines using one common form. This education plan was
      instrumental in providing improved documentation of patient and family education
      in both inpatient and outpatient departments.

PMID- 8981868
TI  - The nurse's role in facilitating compliance in clients with hypertension.
AB  - Afflicting approximately 50 million people, hypertension costs over $500 million
      per year and accounts for the largest number of physician office visits per year
      and the greatest use of prescription drugs. Nurses play a vital role in assessing
      and managing hypertensive clients' and promoting clients' compliance with
      treatment regimens.

PMID- 8981869
TI  - Assessing symptom distress in ambulatory surgery patients.
AB  - Symptom distress constitutes a major problem for patients and their families
      following ambulatory surgery, because managing symptom distress is their
      responsibility. It is essential that the assessment of symptom distress be an
      integral part of ambulatory surgery patient care delivery to decrease
      complications that occur when patients are sent home with unmet care needs.

PMID- 8981870
TI  - Oral nutritional supplements.

PMID- 8981871
TI  - New treatment for obesity: dexfenfluramine (Redux).

PMID- 8981872
TI  - Preferring not-for-profit managed care.

PMID- 8981874
TI  - Hormone replacement therapy: helping your patient decide.

PMID- 8981873
TI  - Assisted suicide and terminating life support: the state of the law.

PMID- 8981876
TI  - Case management in acute care.

PMID- 8981875
TI  - Integrating guidelines into nursing practice.

PMID- 8981877
TI  - Moving research-based practice throughout the health care system.

PMID- 8981878
TI  - Tissue reactions to plastic and metallic wear products of joint endoprostheses.

PMID- 8981879
TI  - The Otto Aufranc Award. Skeletal response to well fixed femoral components
      inserted with and without cement.
AB  - Previous studies evaluating femoral remodeling after total hip arthroplasty have
      used clinical radiographs and dual energy xray absorptiometry. Limitation of
      these techniques make it impossible to quantify the magnitude of bone loss in
      terms of cortical thinning and cortical bone area and bone mineral density
      changes. Femoral cortical bone remodeling after cemented and cementless
      replacement was quantified and possible determinants of bone remodeling in terms
      of clinical and radiographic variables were evaluated. Forty-eight anatomic
      specimen femora from 24 patients with unilateral cemented and cementless hip
      replacements were analyzed. Cortical thickness, cortical bone area, and bone
      mineral density was assessed in 4 quadrants at 5 discrete levels. The maximum
      cortical bone loss by level was at the middle section for the cemented femurs and
      at the midproximal and middle sections for the cementless femurs. However, if one
      examines individual quadrants, the proximal medial cortex still represents the
      specific region of maximal bone loss for both types of implant fixation. The
      posterior cortex had substantially more bone loss, even in the diaphyseal levels,
      than had been previously appreciated. A strong correlation was noted between the
      bone mineral density of the control femur and the percentage decrease of bone
      mineral density in the remodeled femur. Based on this data, it seems that the
      less dense the bone is before hip replacement surgery, the greater the extent of
      bone loss after total hip arthroplasty regardless of the fixation type.

PMID- 8981880
TI  - The John Charnley Award. Natural history of thromboembolic disease after total
      hip arthroplasty.
AB  - In 1079 consecutive patients undergoing total hip arthroplasty between 1984 and
      1992, complications of thromboembolic disease and related anticoagulation were
      reviewed for 6 months after hospital discharge, including cost data. Of 347
      patients having venograms, 78 (22.5%) had positive results and 269 (77.5%) had
      negative results for deep venous thrombosis. In patients with negative venograms,
      3 (1.1%) were readmitted with 2 symptomatic deep venous thromboses and nonfatal
      pulmonary embolism. There were no readmissions among the 55 patients who had
      venographically evident deep venous thrombosis diagnosed and treated with
      outpatient warfarin. Overall, 3 of 324 (0.9%) patients with true positive or
      negative venograms were readmitted for complications of thromboembolic disease.
      In contrast, 12 of 732 (1.6%) patients not receiving contrast venography were
      readmitted, including 9 (1.2%) deep venous thromboses and 3 (0.4%) nonfatal
      pulmonary embolisms. Four of 23 patients (17.4%) with untreated calf deep venous
      thrombosis suffered 2 nonfatal pulmonary embolisms resulting in readmission and 2
      fatal pulmonary embolisms outside the hospital. Untreated calf deep venous
      thrombosis after total hip arthroplasty represents a significant threat of
      extension to more proximal veins and distant embolization. Routine thromboembolic
      disease prophylaxis combined with screening contrast venography and selective
      therapeutic anticoagulation is effective in preventing late thromboembolic
      disease complications and, compared with a strategy of extended prophylaxis for
      all, is cost effective management by reducing exposure of the elderly population
      to outpatient anticoagulant therapy.

PMID- 8981881
TI  - The Frank Stinchfield Award. 3-Dimensional sliding/contact computational
      simulation of total hip wear.
AB  - Polyethylene wear in total hip replacements is a complex, multifactorial process.
      A tribologically grounded finite element formulation was developed to make
      quantitative estimates of polyethylene wear in total hip arthroplasty,
      incorporating the combined influences of contact stress, sliding distance, and a
      surface specific wear coefficient. For loading and sliding distance inputs taken
      directly from human gait data, the computational model showed a strong direct
      proportionality between femoral head size and volumetric wear rate. Other factors
      being equal, reducing the thickness of the polyethylene liner led to increases in
      the computed wear rates, but the effect was far less pronounced than the strong
      increases in wear rate that accompanied head size increases. Compared with human
      gait inputs, the load and sliding distance inputs for a 23 degrees biaxial
      rocking hip simulator led to computed wear rates that were 1.7 times as large,
      and in which the direction of wear was near the cup apex rather than within the
      posterosuperolateral quadrant. In general, the finite element model's results
      emphasize the importance of articulation kinematics, especially sliding distance,
      in the complex process of polyethylene wear in total hip arthroplasty.

PMID- 8981883
TI  - Overview of polyethylene as a bearing material: comparison of sterilization
      methods.
AB  - Polyethylene has been used for more than 30 years as an orthopaedic bearing
      material; however, there has been recent concern regarding the early failure of a
      small percentage of the polyethylene bearings. The damage seen in some retrieved
      polyethylene components has been linked to gamma radiation sterilization in air,
      which was widely used by the industry for years. Gamma radiation in air has been
      documented to cause an increase in oxidation and degradation of mechanical
      properties with time. The degradation of polyethylene initiated by gamma
      sterilization in air has led the orthopaedic industry toward alternative
      sterilization methods, including gamma radiation in an inert gas or vacuum
      environment, ethylene oxide gas sterilization, and gas plasma sterilization. For
      many of these alternative techniques, little clinical performance data exist.
      This study is a comparative evaluation of sterilization methods using the same
      analytic techniques that have been used to document the effects of gamma
      sterilization in air on polyethylene. Fourier transform infrared spectroscopy,
      electron spin resonance, and uniaxial tensile testing are used to compare,
      respectively, the oxidation levels, free radical concentration, and mechanical
      properties of material sterilized by each method. The polyethylene is evaluated
      before sterilization, poststerilization, and postartificial aging. All examined
      alternative sterilization methods, when compared with gamma sterilization in air,
      caused less material degradation during a component's preimplantation shelf life.

PMID- 8981882
TI  - Crevice corrosion of cemented titanium alloy stems in total hip replacements.
AB  - Twenty-eight cemented Muller straight femoral stems of titanium forged alloys
      were mainly revised for causing pain in the patient. The pain pattern differed
      from aseptic loosening and pain recurred only 14.5 months on average after
      implantation. The character of pain was dull, permanent, and increased at rest.
      Some patients reported pain relief while walking. Revisions were performed on
      average 25.5 months after primary implantation. Data from medical records,
      radiographs, histology of tissues taken at revision surgery, intraoperative pH
      measurements, examination of retrieved stems and bone cement fragments were
      gathered. In the radiographs debonding was visible only in 3 cases; a spindle
      shaped thickening of the femora occurred 9 months on average after recurrence of
      pain. After a further 11 months (average), scalloping osteolyses appeared.
      Abraded particles like metallic titanium alloy, titanium corrosion products,
      polymethylmethacrylate, xray contrast medium, and polyethylene were detected.
      Metallic particles dominated in the joint capsule whereas more corrosion products
      impregnated the cement to bone interface. The distal surfaces of the stems were
      corroded at a higher rate, whereas the proximal regions more often were subject
      to abrasion. Measurements of the pH of the corroded stems revealed values of high
      acidity. Recurrence of pain and subperiosteal apposition of bone are due to
      diffusion of acid; subsequent scalloping osteolyses develop due to particle
      induced foreign body granulomas. The mechanism of crevice corrosion of cemented
      titanium based alloys does not seem applicable to cobalt and iron based implant
      alloys. Titanium alloys can no longer be recommended for cementation, but are as
      safe as ever for anchorage without cement.

PMID- 8981884
TI  - Fatigue strength of polyethylene after sterilization by gamma irradiation or
      ethylene oxide.
AB  - The oxidation level of ultrahigh molecular weight polyethylene specimens
      sterilized by gamma irradiation in either air or Ar gas was compared with that of
      unsterilized and ethylene oxide sterilized ultrahigh molecular weight
      polyethylene. The fatigue strength of ultrahigh molecular weight polyethylene
      specimens sterilized by gamma irradiation in air was compared with that of
      unsterilized and ethylene oxide sterilized ultrahigh molecular weight
      polyethylene. At the specimen surface, oxidation was highest for ultrahigh
      molecular weight polyethylene gamma irradiated in air, lower for ultrahigh
      molecular weight polyethylene gamma irradiated in Ar gas, and absent in
      unsterilized and ethylene oxide sterilized ultrahigh molecular weight
      polyethylene. At a depth of 3.5 mm below the specimen surface, oxidation levels
      were equivalent for ultrahigh molecular weight polyethylene gamma irradiated in
      either air or Ar gas whereas unsterilized and ethylene oxide sterilized specimens
      were again unoxidized. Thus, even in an inert atmosphere, oxidative degradation
      of gamma irradiated ultrahigh molecular weight polyethylene occurs. The 10
      million cycle fatigue strength was similar for unsterilized and ethylene oxide
      sterilized ultrahigh molecular weight polyethylene whereas the fatigue strength
      of gamma irradiated in air ultrahigh molecular weight polyethylene was lower.
      Results of this study show that ethylene oxide gas does not degrade ultrahigh
      molecular weight polyethylene whereas gamma radiation in air causes changes in
      the polymer that adversely affect its mechanical properties. Ethylene oxide gas
      is a viable alternative to gamma radiation in air that avoids oxidation and
      fatigue strength degradation known to accompany irradiation of ultrahigh
      molecular weight polyethylene polymer bearing surfaces in total joint implants.

PMID- 8981885
TI  - Engineering issues and wear performance of metal on metal hip implants.
AB  - A major concern in total hip arthroplasty is the generation of polyethylene wear
      particles at the articulating surfaces and resulting macrophage mediated
      periimplant osteolysis. There is renewed interest in metal on metal bearings as a
      solution to this problem in view of their potential for greatly improved wear
      performance. Using a commercially available hip simulator, the wear performance
      of metal on metal femoral head and acetabular cup combinations was evaluated and
      various parameters affecting metal on metal implant wear were identified. Nine
      implants custom manufactured from 2 medical grades of CoCrMo alloy (ASTM F1537-95
      and F75-92) were tested within bovine serum as the lubricant to 3 million cycles
      (equivalent to approximately 3 years of service in vivo). The progressive wear of
      the components was determined by gravimetric methods at approximately every
      300,000 cycles. The wear rates were characterized by an initial period of
      accelerated wear after which a lower steady state wear rate was observed for
      subsequent cycles. The presence of calcium phosphate films on the component
      surfaces, the microstructure of the lower carbon, wrought alloy, and increased
      effective radii (decreased diametral clearances) were identified as factors that
      may be favorable to improved wear performance. The extent of the effect on wear
      of each parameter, however, cannot be discerned at this point and necessitates a
      study in which parametric changes are more tightly controlled. The present study
      suggests that the use of metal on metal articulating surfaces may mitigate the
      problem of osteolysis by offering improved wear performance.

PMID- 8981886
TI  - Modern metal on metal articulation for total hip replacements.
AB  - Between 1991 and 1994, 70 patients received total hip replacements with metal on
      metal articulation. The results of 54 of these patients with 54 hips who have a 2
      to 4-year (2.7-year average) followup are reported. Patients were prospectively
      evaluated using the Harris hip score, a patient self assessment form, and
      radiographs. Hip aspiration was performed preoperatively and 6 to 24 months
      postoperatively in 24 hips with metal on metal articulations. Implant retrieval
      was obtained from 2 patients. Harris hip score averages increased from 49 to 93.
      No patient had revision surgery for loosening, but 1 had revision surgery for
      dislocation. Patient self assessment forms showed 51 of 54 patients scored their
      results as good or excellent. Serial radiographs did not show loosening or
      osteolysis. Wear could not be measured radiographically. Synovial fluid samples
      had metal particles of 1 to 10 microm in 10 hips. Twenty patients had bilateral
      total hip replacements with 1 hip metal on polyethylene articulation, and
      patients could not determine any difference between the hips. Compared with
      historic results of previous metal on metal prostheses, the modern metal on metal
      articulation investigated in this study did not have early acetabular loosening
      or clinical symptoms of component impaction. Retrieval implants and synovial
      fluid analysis suggest early wear was minimal.

PMID- 8981887
TI  - Primary hybrid total hip arthroplasty: an interim followup.
AB  - The senior authors' initial experience with primary hybrid hip replacement in
      patients with osteoarthritis was studied to evaluate the efficacy of the
      procedure. Hybrid total hip arthroplasty (uncemented Harris-Galante acetabular
      component and cemented Iowa precoated femoral component) was performed in 131
      consecutive, nonselected hips in 118 patients with the diagnosis of primary
      osteoarthritis. Followup was performed at 8 to 9 years after the procedure. The
      average age at the time of the procedure was 68 years (range, 45-87 years). There
      were 50 men (55 hips) and 68 women (76 hips). At final followup 19 patients (22
      hips) had died. The femoral component had been revised for aseptic loosening in 8
      hips (6.1%). One additional hip showed definite radiographic loosening. Hence,
      the prevalence of radiographic femoral failure was 6.9% (9 hips). No acetabular
      component had been revised for aseptic loosening and no acetabular component had
      migrated. The senior author continues to perform hybrid total hip arthroplasty in
      all patients with primary osteoarthritis. However, design modifications have been
      made in the femoral component that is used.

PMID- 8981888
TI  - Hybrid primary total hip arthroplasty: a 5- to 9-year followup study.
AB  - One hundred fifty-two hips were reviewed at a minimum of 5 years after hybrid
      primary total hip arthroplasty using uncemented porous coated acetabular
      components and cemented femoral stems to determine the intermediate term
      durability of this method of fixation. Five hips (3.6%) have been revised: 1 for
      dislocation (0.7%), 1 for cup loosening (0.7%), and 3 for femoral loosening
      (2.2%). Clinical results proved to be extremely reliable in this series with 78%
      of the patients reporting no pain and 19.7% reporting slight or occasional pain.
      Radiographic evidence of polyethylene wear was evident in more than 1/2 of cups,
      but significant osteolysis or component loosening was not commonly seen on the
      cup side. On the femoral side incomplete radiolucencies were present in 31%, and
      focal osteolysis in 12.2%, nearly always proximally in Zones 1 and 7. These
      intermediate term results compare favorably on the femoral side and very
      favorably on the acetabular side to prior reported series. These results support
      the continued use of this combination of fixation methods for primary
      arthroplasty, but polyethylene wear and its effects remain a concern regarding
      the long term performance of these arthroplasties.

PMID- 8981889
TI  - Hybrid total hip arthroplasty: 7- to 10-year results.
AB  - One hundred fifty consecutive hybrid total hip arthroplasties in 139 patients
      were performed using an uncemented hemispheric porous coated acetabular component
      (HGP-I) with screws and a femoral component (Precoat) cemented with contemporary
      cementing technique. The average patient age was 67 years (range, 39-85 years).
      No patients were lost to followup. Eighty-six patients (91 hips) were alive for
      an average clinical followup of 103 months (range, 84-127 months); 81 hips had
      corresponding radiographic analysis. The average Harris hip score preoperatively
      was 47 points and increased to 88 points at followup. Ninety-five percent of
      patients had absent or slight pain. Aseptic loosening occurred in 2 femoral
      components (1.3%), 1 of which was revised for secondary osteolysis. Both hips had
      suboptimal cement mantles (C-2 or D grades). No femoral osteolysis was seen in
      stable components. Two acetabular components migrated; 1 secondary to
      preoperative irradiation osteonecrosis and 1 secondary to a bulk autogenous
      graft. Acetabular osteolysis without loosening developed in 2 patients (1.3%).
      Using revision and radiographic loosening as the end point, the probability of
      both components surviving 10 years was 96.9%, 98.6% for the acetabular component,
      and 98.4% for the femoral component. These results show that hybrid total hip
      arthroplasty offers excellent clinical function and exceptional 10-year
      survivorship.

PMID- 8981890
TI  - Hybrid total hip arthroplasty: a 7- to 11-year followup.
AB  - A consecutive series of 125 hybrid total hip arthroplasties were performed in 120
      patients by a single surgeon and were observed for an average of 8.6 years
      (range, 7-11 years). There were 38 men and 82 women with an average age of 71
      years (range, 25-87 years) at the time of surgery. The diagnoses included primary
      and secondary osteoarthritis in 112 patients, osteonecrosis in 5 patients, and
      rheumatoid arthritis in 3 patients. All acetabular components were modular and
      had a Ti shell fixed with an average of 3 screws. The cemented femoral component
      was either Precoat or Precoat Plus with a 28-mm modular CoCr femoral head. The
      patients were prospectively observed clinically using the Harris hip score and
      radiographically using the Hip Society methods. Of the 125 total hip
      arthroplasties, 123 were followed for the entire observation period. The average
      preoperative Harris Hip Score was 37 (range, 15-55) and at the latest followup
      was 92 (range, 65-100). One acetabular component was revised for recurrent
      dislocations 3 years after surgery, and 1 stem was revised for mechanical
      loosening and 1 stem was radiographically loose. There was no evidence of cup
      migration of more than 1 mm. There were no radiolucencies around any of the
      screws. Two sockets had polyethylene wear of 2 mm. Localized pelvic osteolysis
      was noted in 5 hips (4%). The results of this study suggested that hybrid total
      hip replacement is an excellent procedure for reconstruction of the arthritic hip
      with minimal evidence of polyethylene wear and pelvic osteolysis.

PMID- 8981891
TI  - Hybrid total hip replacement: rationale and intermediate clinical results.
AB  - The decade of the 1980s was considered by many hip surgeons to be the decade of
      cement versus cementless. An alternate approach was introduced in which the
      acetabular component used was cementless and the femoral component was fixed with
      cement. This has been called the hybrid total hip replacement. The rationale for
      this approach is presented and intermediate term results (average, 6.6-year
      followup) showed that among 65 consecutive standard hybrid total hip replacements
      in patients who had an average age of 61 years (range, 23-83 years) at the time
      of surgery, no femoral component was revised for aseptic loosening and no
      acetabular component was revised for aseptic loosening. Of the 130 components, 3
      were removed in 2 patients. One patient had both components removed because of
      recurrent dislocation and 1 patient had the acetabular component revised because
      of failure of fixation of the polyethylene liner. The clinical results of this
      approach were excellent in the intermediate term and may have promise for the
      long term.

PMID- 8981892
TI  - Management of limb length inequality during total hip replacement.
AB  - Significant limb length inequality is not an uncommon problem after total hip
      replacement. Preoperative measurement of limb length inequality, preoperative
      planning with radiographic templates, and intraoperative correction with
      measurements of limb lengths before and after the insertion of the trial
      components using special calipers can reduce the incidence and magnitude of this
      problem. A review of 85 consecutive patients who had primary total hip
      arthroplasty in which these techniques were used by a single surgeon, showed that
      43 had limb inequality preoperatively ranging from 0.5 to 7.25 cm, but only 14
      (16%) had limb length inequality after surgery. Eleven limbs (13%) had been
      lengthened 0.5 to 1 cm compared with the contralateral limb. Of the 42 patients
      with equal limb lengths preoperatively, 3 had a lengthened limb postoperatively
      compared with their contralateral limb. Four patients were using lifts on the
      same side because the limb was too short, and 2 were using lifts on the other
      side because the limb was too long. None of the other patients complained about
      limb length inequality. The techniques described above are helpful in minimizing
      limb length inequality during total hip replacements.

PMID- 8981893
TI  - Effects of leg length discrepancies on the forces at the hip joint.
AB  - The authors questioned whether leg length discrepancies of the magnitude
      ordinarily seen after total hip reconstruction (<2 cm) would substantially alter
      hip joint forces. Using conventional gait analysis techniques to ascertain
      intersegmental resultant hip forces and moments, the authors used lifts to
      simulate leg length discrepancies of 2.3, 3.5, and 6.5 cm in 7 normal subjects.
      The 2.3-cm lift produced no changes. On the side of the lift (long limb), the 3.5
      and 6.5-cm lifts modestly decreased mean peak intersegmental resultant hip
      forces by 6% and 12%, respectively, but not moments. The changes were, however,
      variable, with a few subjects showing increases and the rest showing decreases in
      selected forces or moments. On the side opposite to the lift (short limb), the
      3.5- and 6.5-cm lifts increased mean peak intersegmental resultant hip forces by
      2% to 12%, but not moments except in 1 case (8%). It is concluded that leg length
      discrepancies of the sort commonly seen after total hip reconstruction would
      likely cause no substantial changes in hip forces.

PMID- 8981894
TI  - Fixation stability of olecranon osteotomies.
AB  - Eighteen pairs of fresh frozen human upper extremities were selected and each
      randomized to 2 of 3 olecranon osteotomy and fixation technique groups: (1)
      transverse osteotomy with 0.062 Kirschner wire and tension band fixation; (2)
      chevron osteotomy with 6.5-mm cancellous lag screw and tension band fixation; and
      (3) oblique intraarticular osteotomy with 3.5-mm cortical lag screw and tension
      band fixation. The arms were mounted with the elbow at 90 degrees flexion and the
      wrist constrained; a dual linear displacement transducer across the osteotomy was
      used to determine angulation, translational displacement, and the total gap size.
      First the brachialis and then the triceps were incrementally loaded to 10 kg
      using a pulley and cable system to control force direction; the muscle load
      versus osteotomy displacement was recorded. Cycling with 10 kg was repeated 20
      times with the brachialis and triceps alternately loaded and the osteotomy
      displacement remeasured. There were no statistically significant differences
      between the amounts of displacement for the 3 osteotomy and fixation techniques
      caused by either muscle action. The total displacement caused by the brachialis
      load for all techniques was appreciably greater than that of the triceps load. No
      significant increase in displacements occurred after 20 load cycles. These
      results suggest all 3 olecranon osteotomy and fixation techniques offer
      comparable stability, so the choice of technique should be left to the surgeon's
      preference.

PMID- 8981895
TI  - Long term evaluation of repaired distal biceps brachii tendon ruptures.
AB  - A long term evaluation was performed on 8 patients who had rupture of the distal
      biceps tendon repaired using the 2-incision technique. The length of followup
      ranged from 1 to 11 years with an average of 6 years. Goniometric range of motion
      and isokinetic strength testing were performed on all patients. All patients
      attained a full arc of elbow flexion and extension. Supination was diminished
      more than 30 degrees in 3 patients and pronation was diminished more than 30
      degrees in 1 patient. Subjectively, 6 of 8 patients were completely satisfied
      with the function of their involved arm. Strength and work performed during
      repetitive exercise were regained to the expected normal levels in elbow flexion.
      Six of 8 patients continued to have less strength in supination of the injured
      arm than the uninjured arm. All 8 patients performed less total work with
      repetitive supination of the injured arm than the uninjured arm.

PMID- 8981896
TI  - Physical signs in lumbar disc hernia.
AB  - In a prospective study of 163 consecutive patients operated on because they were
      thought to have lumbar disc hernia, the authors investigated whether physical
      signs could predict the degree of hernia (complete hernia, incomplete hernia,
      protruded disc, and normal disc) found at surgery. Stepwise discriminant analysis
      showed that there were only 2 physical signs of diagnostic value: lumbar range of
      motion and crossed Lasegue sign. By these signs, 74% of the uncontained hernias
      and 68% of the contained hernias could be correctly classified. Discrimination
      also was made between intact annuli (negative exploration and protruded disc)
      versus ruptured annuli (incomplete hernias and complete hernias). Again, lumbar
      range of motion and crossed Lasegue sign were the only significant parameters,
      predicting 71% of the ruptured annuli and 80% of the intact annuli. These 2
      physical signs are important because the degree of the hernia is the most
      important prognostic factor for the outcome of lumbar disc surgery. The degree of
      the hernia also has an impact on the choice of invasive therapy: open surgery,
      percutaneous surgery, or enzymatic nucleolysis. Neurologic signs often were
      absent, showed low correlation to the degree of the hernia, and had a limited
      value for predicting the level of the hernia. However, they are important for the
      differential diagnosis in distinguishing between radicular and referred pain.

PMID- 8981897
TI  - Dysplasia epiphysealis hemimelica of the sacroiliac joint: a case report.
AB  - Dysplasia epiphysealis hemimelica is a rare developmental abnormality involving
      aberrant epiphyseal cartilage growth. This is the first known case report
      describing dysplasia epiphysealis hemimelica arising from the sacroiliac joint.
      The operative technique described through an indirect computed tomography guided
      approach limited the exposure and potential morbidity involving the sacroiliac
      joint.

PMID- 8981898
TI  - Trochanteric osteotomy and wire fixation: a comparison of 2 techniques.
AB  - Between 1986 and 1989, 190 patients (214 hips) with the diagnosis of
      osteoarthritis or posttraumatic arthritis underwent cemented Charnley total hip
      replacement surgeries via the biplane or single plane transtrochanteric approach.
      The technique of surgery was identical in every aspect except for the technique
      of the trochanteric osteotomy and reattachment. The results indicate that there
      was no significant difference in union rates between the 2 groups. Six (6.4%)
      patients in the biplane group and 7 (6.2%) patients in the single plane group had
      obvious evidence of nonunion at the 1-year evaluation. This study suggests no
      significant difference in union rate between a group of patients with biplane
      osteotomy and a closely paired group of patients with single plane osteotomy.
      Other equally important factors also may influence the rate of union of the
      trochanter in total hip arthroplasty.

PMID- 8981899
TI  - Primary cementless hip arthroplasty with a titanium plasma sprayed prosthesis.
AB  - One hundred two patients underwent 105 primary uncemented total hip
      arthroplasties and were reviewed at a minimum of 5 years after operation (mean,
      6.1 years). The components were titanium alloy with a titanium plasma spray
      coating. The acetabular revision rate was 11.4%. Acetabular cavitary lytic
      lesions were identified in 25.5% at 5 years. All acetabular revisions were
      performed for a combination of wear and osteolysis. One femoral revision was
      performed to facilitate an acetabular revision, but the femoral revision rate for
      aseptic loosening was 0%. In addition, no femoral components had subsided or were
      thought to be loose radiographically. Thigh pain was present in 4% at 5 years.
      Despite the 25.5% incidence of acetabular osteolysis, distal femoral lysis was
      not seen and only 5% showed focal osteolysis in the trochanteric region proximal
      to the circumferential porous coating of the femoral component. Component design
      features were thought to be critical to the excellent performance of the femoral
      component and to the poor performance of the acetabular component.

PMID- 8981901
TI  - Catastrophic failure of a conforming type of total knee replacement: a case
      report.
AB  - A case study is presented to illustrate the concept of femoral component failure
      secondary to polyethylene wear in a 67 year old man, 13 years after he had
      conforming type total knee replacements. This case illustrates the theory that
      this observed problem may be a leading cause of failure in conforming and
      nonconforming total knee replacements in the future.

PMID- 8981900
TI  - Dislocations and the femoral head size in primary total hip arthroplasty.
AB  - The dislocation rate of 3197 Charnley prostheses with 22 mm head in which the
      surgery was done between 1979 and 1991 in 2 orthopaedic centers was compared with
      that of 2875 Lubinus prostheses with 32 mm head in which the surgery was done
      between 1980 to 1991 in 3 other centers. A 1-year followup showed an equal rate
      of dislocation (2.4%-2.5%) in the 2 groups and included 75% of the 201 dislocated
      hips. Almost all of the late dislocations occurred with the Charnley prosthesis,
      resulting in a total dislocation rate of 3.7% compared with 2.9% with the Lubinus
      prosthesis. Regardless of the type of prosthesis used, there was a higher risk of
      dislocation in patients with nonhealed hip fractures and in arthroplasties
      performed by less experienced surgeons. When these 2 variables were removed, the
      small femoral head was not associated with an increased risk of dislocation.
      However, there were 77 of 118 (65%) recurrent dislocations in the Charnley group,
      compared with 37 of 83 (45%) in the Lubinus group, and the relative risk of a
      dislocated hip arthroplasty becoming recurrent increased by 2.3 times if the
      small femoral head was used. The number of reoperations also were doubled in this
      group. Almost 4 times as many dislocations were documented within 2 weeks after
      surgery after any type of prosthesis inserted through a posterior approach
      compared with the transtrochanteric approach, but there was no increase in rate
      of recurrence or revision.

PMID- 8981902
TI  - Fibrosarcoma of the toe: a destructive lesion of the distal phalanx.
AB  - A rare case of well differentiated fibrosarcoma occurring in the left second toe
      is described in a 12-year-old boy who presented with a destructive lesion that
      had almost totally destroyed the distal phalanx, except for the epiphysis.
      Amputated specimens showed microscopic evidence of proliferation of uniform
      spindle cells arranged in both fascicles and a characteristic herringbone pattern
      with a small number of mitotic figures. This tumor did not show any specific
      immunoreactivity except for vimentin and had basic ultrastructural
      characteristics of fibroblasts and myofibroblasts. The tumor was treated by
      amputation at the middle phalanx level and had not recurred 3 years later. From
      the presenting radiographic features, some benign neoplasms and reactive lesions
      were considered in the differential diagnosis. Only results from the pathologic
      examination were useful in reaching a correct diagnosis.

PMID- 8981903
TI  - Effect of cefazolin and vancomycin on osteoblasts in vitro.
AB  - The effect of cefazolin and vancomycin on osteoblast-like cells was studied.
      Cells from the MG-63 human osteosarcoma cell line were grown in antibiotic free
      media and exposed to concentrations of cefazolin and vancomycin at order of
      magnitude intervals between 0 and 10,000 microg/ml. For cefazolin, a second
      interval was performed between 100 and 1000 microg/ml to define toxic levels more
      accurately. Cell number and 3H-thymidine incorporation at 0, 24, and 72 hours
      were determined. The results of this study show that local levels of vancomycin
      of 1000 microg/ml and less have little or no effect on osteoblast replication,
      and concentrations of 10,000 microg/ml cause cell death. Concentrations of
      cefazolin of 100 microg/ml and less have little or no effect on osteoblast
      replication, 200 microg/ml significantly decrease cell replication, and 10,000
      microg/ml cause cell death. The authors conclude that vancomycin is less toxic
      than is cefazolin to osteoblasts at higher concentrations and may be a better
      antibiotic for local administration in the treatment of similarly sensitive
      bacterial infections.

PMID- 8981904
TI  - Basic fibroblast growth factor promotes bone ingrowth in porous hydroxyapatite.
AB  - The effect of basic fibroblast growth factor on tissue ingrowth and
      differentiation in porous hydroxyapatite of coralline origin was studied in a
      bone chamber model. The hydroxyapatite with or without basic fibroblast growth
      factor was placed in 22 mm3 titanium bone conduction chambers implanted
      bilaterally in rat tibiae. Ingrowing bone could enter the cylindrical interior of
      the chamber only at 1 end. It then penetrated the porous hydroxyapatite inside
      the chamber. The distance that the ingrown tissue had reached into the material
      then was measured on histologic slides. Because fibrous tissue always reached
      further into the material than did bone, both total tissue ingrowth and bone
      ingrowth distances were measured. In implants supplemented with 0.04 microg basic
      fibroblast growth factor in a hyaluronate gel carrier, the bone ingrowth distance
      was increased by 70% at 6 weeks, as compared with paired controls in the
      contralateral leg. The total tissue ingrowth distance also was increased by 58%.
      When the dose of basic fibroblast growth factor was increased to 1.0 microg,
      still using the hyaluronate carrier, there was no difference in bone ingrowth
      compared with controls, but this dose still increased the total tissue ingrowth.
      In hydroxyapatite with 1.5 microg basic fibroblast growth factor without
      hyaluronate gel at 4 weeks, no increase in bone ingrowth was shown, but total
      tissue ingrowth was increased. At 6 weeks, bone ingrowth and total tissue
      ingrowth were increased by 41% and 33%, respectively. With a lower dose of 0.15
      microg without carrier, only the total ingrowth distance was increased. The
      results suggest that basic fibroblast growth factor may promote tissue ingrowth
      into porous hydroxyapatite and that bone ingrowth may be increased by appropriate
      doses. The hyaluronate gel carrier reduced the optimal dose.

PMID- 8981905
TI  - Congenital metatarsus adductus in early human fetal development: a histologic
      study.
AB  - Two feet with congenital metatarsus adductus from fetuses at early development
      (16 and 19 weeks of gestation) were studied by making serial histologic sections
      in the horizontal plane of the foot. It was observed that the shape of the medial
      cuneiform was altered and the first cuneometatarsal joint tilted toward the
      medial and dorsal directions. The first metatarsal appeared normal, whereas the
      other metatarsals were deformed in slight adduction at the metaphyseal level.
      Subluxation at the other cuneometatarsal joints and naviculocuneiform joint was
      not observed, and the navicular showed no signs of medial or lateral displacement
      in relation to the head of the talus. No histologic abnormalities of the joint
      capsules, ligaments, or tendons were observed. On the basis of these pathologic
      findings, the possibility of a developmental abnormality of the medial cuneiform
      as a pathogenic factor for the congenital metatarsus adductus deformity should be
      considered.

PMID- 8981906
TI  - Incidental cartilage lesion in a 71-year-old man.

PMID- 8981907
TI  - Surprise? Bacteria glycosylate proteins too.

PMID- 8981908
TI  - Effects of fluid dynamic forces on vascular cell adhesion.

PMID- 8981909
TI  - Plasminogen activator inhibitor-1 in acute hyperoxic mouse lung injury.
AB  - Hyperoxia-induced lung disease is associated with prominent intraalveolar fibrin
      deposition. Fibrin turnover is tightly regulated by the concerted action of
      proteases and antiproteases, and inhibition of plasmin-mediated proteolysis could
      account for fibrin accumulation in lung alveoli. We show here that lungs of mice
      exposed to hyperoxia overproduce plasminogen activator inhibitor-1 (PAI-1), and
      that PAI-1 upregulation impairs fibrinolytic activity in the alveolar
      compartment. To explore whether increased PAI-1 production is a causal or only a
      correlative event for impaired intraalveolar fibrinolysis and the development of
      hyaline membrane disease, we studied mice genetically deficient in PAI-1. We
      found that these mice fail to develop intraalveolar fibrin deposits in response
      to hyperoxia and that they are more resistant to the lethal effects of hyperoxic
      stress. These observations provide clear and novel evidence for the pathogenic
      contribution of PAI-1 in the development of hyaline membrane disease. They
      identify PAI-1 as a major deleterious mediator of hyperoxic lung injury.

PMID- 8981910
TI  - Identification and localization of polycystin, the PKD1 gene product.
AB  - Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1
      gene (PKD1) is the cardinal member of a novel class of proteins. As a first step
      towards elucidating the function of polycystin and the pathogenesis of ADPKD,
      three types of information were collected in the current study: the subcellular
      localization of polycystin, the spatial and temporal distribution of the protein
      within normal tissues and the effects of ADPKD mutations on the pattern of
      expression in affected tissues. Antisera directed against a synthetic peptide and
      two recombinant proteins of different domains of polycystin revealed the presence
      of an approximately 400-kD protein (polycystin) in the membrane fractions of
      normal fetal, adult, and ADPKD kidneys. Immunohistological studies localized
      polycystin to renal tubular epithelia, hepatic bile ductules, and pancreatic
      ducts, all sites of cystic changes in ADPKD, as well as in tissues such as skin
      that are not known to be affected in ADPKD. By electron microscopy, polycystin
      was predominantly associated with plasma membranes. Polycystin was significantly
      less abundant in adult than in fetal epithelia. In contrast, polycystin was
      overexpressed in most, but not all, cysts in ADPKD kidneys.

PMID- 8981911
TI  - Proliferation induced by keratinocyte growth factor enhances in vivo retroviral
      mediated gene transfer to mouse hepatocytes.
AB  - Retroviral gene transfer to liver without prior injury has not yet been
      accomplished. We hypothesized that recombinant human keratinocyte growth factor
      would stimulate proliferation of hepatocytes and allow for efficient in vivo gene
      transfer with high titer murine Moloney retroviral vectors. This report shows
      that 48 h after intravenous injection of keratinocyte growth factor, hepatocyte
      proliferation increased approximately 40-fold compared to non-stimulated livers.
      When keratinocyte growth factor treatment was followed by intravenous injection
      of high titer (1 x 10(8) colony forming units/ml) retrovirus coding for the
      Escherichia Coli beta-galactosidase gene, there was a 600-fold increase in beta
      galactosidase expression, with 2% of hepatocytes transduced. Thus, by exploiting
      the mitogenic properties of keratinocyte growth factor, retrovirus-mediated gene
      transfer to liver may be accomplished in vivo without the use of partial
      hepatectomy or pretreatment with other toxins to induce hepatocyte cell division.

PMID- 8981912
TI  - DNA aptamers block L-selectin function in vivo. Inhibition of human lymphocyte
      trafficking in SCID mice.
AB  - Selectins participate in the initial events leading to leukocyte extravasation
      from the blood into tissues. Thus the selectins have generated much interest as
      targets for antiinflammatory agents. Therapeutic molecules based on the monomeric
      carbohydrate ligand sialyl Lewis X (SLe(X)) have low affinities and are not
      specific for a given selectin. Using SELEX (Systematic Evolution of Ligands by
      EXponential Enrichment) technology, we have generated aptamers specific for L
      selectin that require divalent cations for binding and have low nanomolar
      affinity. In vitro, the deoxyoligonucleotides inhibit L-selectin binding to
      immobilized SLe(X) in static assays and inhibit L-selectin-mediated rolling of
      human lymphocytes and neutrophils on cytokine-activated endothelial cells in flow
      based assays. These aptamers also block L-selectin-dependent lymphocyte
      trafficking in vivo, indicating their potential utility as therapeutics.

PMID- 8981913
TI  - Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a
      murine model.
AB  - Activation of naive T cells requires at least two signals. In addition to the
      well characterized interaction of the T cell antigen receptor with the
      antigen/MHC expressed on an antigen-presenting cell, T cell activation also
      requires costimulation by a second set of signals. The best characterized
      costimulatory receptor is CD28, which binds to a family of B7 ligands expressed
      on antigen-presenting cells. In asthma, although activated T cells play a role in
      the initiation and maintenance of airway inflammation, the importance of T cell
      costimulation in bronchial hyperresponsiveness had not been characterized.
      Therefore, we tested the hypothesis that inhibition of the CD28:B7 costimulatory
      pathway would abrogate airway hyperresponsiveness. Our results show that blockade
      of costimulation with CTLA4-Ig, a fusion protein known to prevent costimulation
      by blocking CD28:B7 interactions, inhibits airway hyperresponsiveness,
      inflammatory infiltration, expansion of thoracic lymphocytes, and allergen
      specific responsiveness of thoracic T cells in this murine model of allergic
      asthma.

PMID- 8981914
TI  - Induction of neonatal tolerance by plasmid DNA vaccination of mice.
AB  - Plasmid DNA vaccines capable of preventing viral, bacterial, and parasitic
      infections are currently under development. Our labs have shown that a plasmid
      DNA vaccine encoding the circumsporozoite protein of the malaria parasite elicits
      protective immunity against live sporozoite challenge in adult BALB/c mice. We
      now find that the same DNA vaccine induces tolerance rather than immunity when
      administered to 2-5 d-old mice. Neonatally tolerized animals were unable to mount
      antibody, cytokine or cytotoxic responses when rechallenged with DNA vaccine in
      vitro or in vivo. Tolerance was specific for immunogenic epitopes expressed by
      the vaccine-encoded, endogenously produced antigen. Mice challenged with
      exogenous circumsporozoite protein produced antibodies against a different set of
      epitopes, and were not tolerized. These findings demonstrate important
      differences in the nature and specificity of the immune response elicited by DNA
      vaccines versus conventional protein immunogens.

PMID- 8981915
TI  - Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in
      patients with acquired growth hormone deficiency. A double-blind, placebo
      controlled study.
AB  - We studied the effects of recombinant growth hormone on systemic nitric oxide
      (NO) formation and hemodynamics in a double-blind, placebo-controlled trial in
      adult patients with acquired growth hormone deficiency. 30 patients were randomly
      allocated to either recombinant human growth hormone (r-hGH; 2.0 IU/d) or placebo
      for 12 mo. In the subsequent 12 mo, the study was continued with both groups of
      patients receiving r-hGH. In months 1, 3, 6, 9, and 12 of each year, urine and
      plasma samples were collected for the determination of urinary nitrate and cyclic
      GMP as indices of systemic NO production, and of plasma IGF-1 levels. Cardiac
      output was measured in months 1, 12, and 24 by echocardiography. r-hGH induced a
      fourfold increase in plasma IGF-1 concentrations within the first month of
      treatment. Urinary nitrate and cyclic GMP excretion rates were low at baseline in
      growth hormone-deficient patients (nitrate, 96.8+/-7.4 micromol/mmol creatinine;
      cyclic GMP, 63.6+/-7.1 nmol/mmol creatinine) as compared with healthy controls
      (nitrate, 167.3+/-7.5 micromol/mmol creatinine; cyclic GMP, 155.2+/-6.9 nmol/mmol
      creatinine). These indices of NO production were significantly increased by r
      hGH, within the first 12 mo in the GH group, and within the second 12 mo in the
      placebo group. While systolic and diastolic blood pressure were not significantly
      altered by r-hGH, cardiac output significantly increased by 30-40%, and total
      peripheral resistance decreased by approximately 30% in both groups when they
      were assigned to r-hGH treatment. In the second study year, when both groups were
      given r-hGH, there were no significant differences in plasma IGF-1, urinary
      nitrate, or cyclic GMP excretion, or hemodynamic parameters between both groups.
      In conclusion, systemic NO formation is decreased in untreated growth hormone
      deficient patients. Treatment with recombinant human growth hormone normalizes
      urinary nitrate and cyclic GMP excretion, possibly via IGF-1 stimulation of
      endothelial NO formation, and concomitantly decreases peripheral arterial
      resistance. Increased NO formation may be one reason for improved cardiovascular
      performance of patients with acquired hypopituitarism during growth hormone
      therapy.

PMID- 8981916
TI  - Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome.
AB  - Neutrophil (PMNL) function defects occur as a consequence of HIV infection. This
      study examined PMNL apoptosis in patients with the acquired immunodeficiency
      syndrome (AIDS) to determine if accelerated apoptosis contributes to impaired
      function. PMNL were isolated from 10 HIV-infected patients with CD4+ lymphocyte
      counts < 200/mm3 without signs of active infection and 7 healthy volunteers. PMNL
      were stained with acridine orange and ethidium bromide after 0, 3, 6, and 18 h in
      culture, and examined for the morphologic changes of apoptosis and viability by
      fluorescent microscopy. Apoptosis was also demonstrated by electron microscopy,
      flow cytometry, and DNA gel electrophoresis. Apoptosis was minimal at 0 h, but
      PMNL from AIDS patients exhibited significantly greater apoptosis than controls
      at 3 h (22.5+/-11.5 vs. 8.9+/-6.9%, P = 0.015), 6 h (38.1+/-14.2 vs. 18.1+/-4.5%,
      P = 0.003), and 18 h (71.3+/-19.0 vs. 38.8+/-16.7%, P = 0.002). Viabilities were
      > or = 88.0% for both groups from 0-6 h, but by 18 h viability was significantly
      decreased for the HIV group (58.8+/-12.4 vs. 83.5+/-10.4%, P = 0.001) due to an
      increase in non-viable apoptotic cells. Incubation with serum from AIDS patients
      had no effect on control PMNL, and incubation with control serum did not reduce
      the rate of apoptosis of PMNL from AIDS patients. Incubation with granulocyte
      colony-stimulating factor (G-CSF) in vitro significantly decreased apoptosis for
      PMNL from AIDS patients. PMNL from patients with AIDS exhibit markedly
      accelerated apoptosis ex vivo. In vivo, apoptosis and functional impairment of
      PMNL may contribute to the risk of secondary infections, and cytokine therapy may
      be of potential clinical benefit in this circumstance.

PMID- 8981917
TI  - Intracellular cleavage of hepatitis C virus RNA and inhibition of viral protein
      translation by hammerhead ribozymes.
AB  - To determine the effects of hammerhead ribozymes against hepatitis C virus (HCV)
      RNA on viral protein translation, a luciferase reporter gene vector, pCMV/T7
      NCRCdelta-luc, was constructed containing the 5'-noncoding region (5'-NCR) and
      part of the core region of HCV. Four ribozymes, Rz1-Rz4, were designed to cleave
      at nucleotide positions 136-160, 313-337, 496-520, and 373-388, respectively.
      Each ribozyme cleaved the target RNA at expected positions under cell-free
      conditions. Rz2 and Rz4 significantly suppressed translation of NCRCdelta-luc RNA
      by 71 and 49%, respectively. Translation of control luciferase mRNA lacking viral
      elements was not affected by the ribozymes. Furthermore, when NCRCdelta-luc RNA
      and ribozymes were cotransfected into cells, Rz2 and Rz4 significantly suppressed
      expression by 73 and 56%, respectively. In contrast, cleavage-deficient ribozymes
      with a point mutation in the hammerhead domain had no significant effect. To
      determine the effects of endogenously produced ribozymes, eukaryotic expression
      vectors for Rz2 and Rz4 were constructed. Cotransfection of the vectors with
      CMV/T7-NCRCdelta-luc showed suppression of luciferase activities to 50 and 61%,
      respectively. Moreover, transfection of pCMV/T7-NCRCdelta-luc into stable Rz2 and
      Rz4 producer cells also showed substantial inhibition of luciferase activity.
      Ribozymes directed against the HCV genome can substantially and specifically
      inhibit viral gene expression under intracellular conditions.

PMID- 8981918
TI  - Characterization of SR 121463A, a highly potent and selective, orally active
      vasopressin V2 receptor antagonist.
AB  - SR 121463A, a potent and selective, orally active, nonpeptide vasopressin V2
      receptor antagonist, has been characterized in several in vitro and in vivo
      models. This compound displayed highly competitive and selective affinity for V2
      receptors in rat, bovine and human kidney (0.6 < or = Ki [nM] < or = 4.1). In
      this latter preparation, SR 121463A potently antagonized arginine vasopressin
      (AVP)-stimulated adenylyl cyclase activity (Ki = 0.26+/-0.04 nM) without any
      intrinsic agonistic effect. In autoradiographic experiments performed in rat
      kidney sections, SR 121463A displaced [3H]AVP labeling especially in the medullo
      papillary region and confirmed that it is a suitable tool for mapping V2
      receptors. In comparison, the nonpeptide V2 antagonist, OPC-31260, showed much
      lower affinity for animal and human renal V2 receptors and lower efficacy to
      inhibit vasopressin-stimulated adenylyl cyclase (Ki in the 10 nanomolar range).
      Moreover, OPC-31260 exhibited a poor V2 selectivity profile and can be considered
      as a V2/V1a ligand. In normally hydrated conscious rats, SR 121463A induced
      powerful aquaresis after intravenous (0.003-0.3 mg/kg) or oral (0.03-10 mg/kg)
      administration. The effect was dose-dependent and lasted about 6 hours at the
      dose of 3 mg/kg p.o. OPC-31260 had a similar aquaretic profile but with markedly
      lower oral efficacy. The action of SR 121463A was purely aquaretic with no
      changes in urine Na+ and K+ excretions unlike that of known diuretic agents such
      as furosemide or hydrochlorothiazide. In addition, no antidiuretic properties
      have been detected with SR 121463A in vasopressin-deficient Brattleboro rats.
      Thus, SR 121463A is the most potent and selective, orally active V2 antagonist
      yet described and could be a powerful tool for exploring V2 receptors and the
      therapeutical usefulness of V2 blocker aquaretic agents in water-retaining
      diseases.

PMID- 8981919
TI  - Relaxin induces an extracellular matrix-degrading phenotype in human lung
      fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo.
AB  - Pulmonary fibrosis is the common end stage of a number of pneumopathies. In this
      study, we examined the ability of the human cytokine, relaxin, to block
      extracellular matrix deposition by human lung fibroblasts in vitro, and to
      inhibit lung fibrosis in a bleomycin-induced murine model. In vitro, relaxin (1
      100 ng/ml) inhibited the transforming growth factor-beta-mediated over-expression
      of interstitial collagen types I and III by human lung fibroblasts by up to 45%
      in a dose-dependent manner. Relaxin did not affect basal levels of collagen
      expression in the absence of TGF-beta-induced stimulation. Relaxin also blocked
      transforming growth factor-beta-induced upregulation of fibronectin by 80% at the
      highest relaxin dose tested (100 ng/ml). The expression of matrix
      metalloproteinase-1, or procollagenase, was stimulated in a biphasic, dose
      dependent manner by relaxin. In vivo, relaxin, at a steady state circulating
      concentration of approximately 50 ng/ml, inhibited bleomycin-mediated alveolar
      thickening compared with the vehicle only control group (P < 0.05). Relaxin also
      restored bleomycin-induced collagen accumulation, as measured by lung
      hydroxyproline content, to normal levels (P < 0.05). In summary, relaxin induced
      a matrix degradative phenotype in human lung fibroblasts in vitro and inhibited
      bleomycin-induced fibrosis in a murine model in vivo. These data indicate that
      relaxin may be efficacious in the treatment of pathologies characterized by lung
      fibrosis.

PMID- 8981920
TI  - HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human
      beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m.
AB  - MHC class I allele, HLA-B27, is strongly associated with a group of human
      diseases called spondyloarthropathies. Some of these diseases have an onset after
      an enteric or genitourinary infection. In the present study, we describe
      spontaneous disease in HLA-B27 transgenic mice where endogenous beta2
      microglobulin (beta2m) gene was replaced with transgenic human beta2m gene. These
      mice showed cell surface expression of HLA-B27 similar to that of human
      peripheral blood mononuclear cells. In addition, free heavy chains (HCs) of HLA
      B27 were also expressed on thymic epithelium and on a subpopulation of B27
      expressing PBLs. These mice developed spontaneous arthritis and nail changes in
      the rear paws. Arthritis occurred primarily in male animals and only when mice
      were transferred from the pathogen-free barrier facility to the conventional
      area. Transgenic mice expressing HLA-B27 with mouse beta2m have undetectable
      levels of free HCs on the cell surface and do not develop arthritis. In vivo
      treatment with anti-HC-specific antibody delayed the onset of disease. Our data
      demonstrate specific involvement of HLA-B27 'free' HCs in the disease process.

PMID- 8981921
TI  - Muscarinic receptor modulation of basal and beta-adrenergic stimulated function
      of the failing human left ventricle.
AB  - The objective of this study was to evaluate the effect of muscarinic receptor
      modulation on basal and beta-adrenergic stimulated left ventricular function in
      patients with heart failure. 21 heart failure patients and 14 subjects with
      normal ventricular function were studied. In Protocol 1 intracoronary
      acetylcholine resulted in a 60+/-8% inhibition of the left ventricular +dP/dt
      response to intracoronary dobutamine in the normal group, and a similar 70+/-13%
      inhibition in the heart failure group. Acetylcholine also attenuated the
      dobutamine-mediated acceleration of isovolumic relaxation (Tau) in both groups.
      Acetylcholine alone had no effect on Tau in the normal group, while it prolonged
      Tau in the heart failure group. In Protocol 2 intracoronary atropine resulted in
      a 35+/-10% augmentation of the inotropic response to dobutamine in the normal
      group, versus a non-significant 12+/-15% augmentation of the dobutamine response
      in the heart failure group. In Protocol 3, in 6 heart failure patients, both
      effects of acetylcholine, the slowing of ventricular relaxation and the
      inhibition of beta-adrenergic responses, were reversed by the addition of
      atropine. Therefore, in the failing human left ventricle muscarinic stimulation
      has an independent negative lusitropic effect and antagonizes the effects of beta
      adrenergic stimulation.

PMID- 8981922
TI  - Differences in endogenous peptides presented by HLA-B*2705 and B*2703 allelic
      variants. Implications for susceptibility to spondylarthropathies.
AB  - The association between HLA-B27 and spondylarthropathies is currently being
      reinvestigated in the light of HLA-B27 subtyping. At least 11 different subtypes
      have been described among which B*2703, B*2706, and B*2709 could be less closely
      associated with disease at the population level. Differences in the presentation
      of antigenic peptides by these subtypes could be related to differences in
      disease susceptibility. We focused our work on the comparison of B*2705 and
      B*2703 which differ at a single position at residue 59 in pocket A of the peptide
      binding groove. Endogenous peptides from the human C1R line transfected by B*2705
      or B*2703 were acid-eluted and separated by HPLC. Major individual fractions were
      sequenced by Edman NH2-terminal degradation. Differences observed between B*2705
      versus B*2703 individual ligands were confirmed in an in vitro stabilization
      assay with T2-B*2705 or B*2703 transfected cells in the presence of synthetic
      peptides. One B*2705 associated peptide is derived from the sequence 169-179 in
      the second extracellular domain of several HLA class I molecules including HLA
      B27. This sequence (RRYLENGKETL) is highly homologous to a previously reported
      sequence (LRRYLENGK) sharing similarities with proteins from enteric bacteria. We
      show here that it is naturally presented as a major endogenous peptide by B*2705
      and B*2702 disease-associated subtypes and not by B*2703.

PMID- 8981923
TI  - Growth inhibitory properties of endothelin-1 in activated human hepatic stellate
      cells: a cyclic adenosine monophosphate-mediated pathway. Inhibition of both
      extracellular signal-regulated kinase and c-Jun kinase and upregulation of
      endothelin B receptors.
AB  - During chronic liver diseases, hepatic stellate cells (HSC) acquire an activated
      myofibroblast-like phenotype, proliferate, and synthetize fibrosis components. We
      have shown that endothelin-1 (ET-1) inhibits the proliferation of activated human
      HSC via endothelin B (ETB) receptors. We now investigate the transduction pathway
      involved in the growth inhibitory effect of ET-1 in activated HSC. Endothelin-1
      and the ETB receptor agonist, sarafotoxin-S6C, increased synthesis of PGI2 and
      PGE2, leading to elevation of cAMP. The cyclooxygenase inhibitor ibuprofen and
      the adenylyl cyclase inhibitor SQ22536 both blunted the growth inhibitory effect
      of ET-1. Analysis of early steps associated with growth inhibition indicated
      that: (a) similar to ET-1, forskolin decreased c-jun mRNA induction without
      affecting c-fos and krox 24 mRNA expression; (b) ET-1, sarafotoxin-S6C, as well
      as forskolin, reduced activation of both c-Jun kinase and extracellular signal
      regulated kinase. Finally, forskolin, PGI2, and PGE2 raised by fivefold the
      number of ET binding sites after 6 h, and increased the proportion of ETB
      receptors from 50% in control cells to 80% in treated cells. In conclusion, ET-1
      inhibits proliferation of activated HSC via ETB receptors, through a
      prostaglandin/cAMP pathway that leads to inhibition of both extracellular signal
      regulated kinase and c-Jun kinase activities. Upregulation of ETB receptors by
      prostaglandin/cAMP raises the possibility of a positive feedback loop that would
      amplify the growth inhibitory response. These results suggest that ET-1 and
      agents that increase cAMP might be of interest to limit proliferation of
      activated HSC during chronic liver diseases.

PMID- 8981924
TI  - Spinal cord adenosine receptor stimulation in rats inhibits peripheral neutrophil
      accumulation. The role of N-methyl-D-aspartate receptors.
AB  - The effect of spinal adenosine receptor ligation on peripheral leukocyte
      accumulation was studied in two rat models of inflammation. Neutrophil
      infiltration into dermal inflammatory sites was signficantly reduced by adenosine
      A1 receptor agonists injected through intrathecal catheters. These effects were
      reversed by N-methyl-D-aspartate (NMDA), and were mimicked by (+/-)-2-amino-5
      phosphonopentanoic acid (AP-5), a glutamate NMDA receptor antagonist. Peripheral
      adenosine levels, as measured in air pouch exudates, decreased markedly in
      inflamed pouches but remained near normal after intrathecal treatment with AP-5.
      Moreover, the antiinflammatory effects of intrathecal A1 receptor agonists and AP
      5 were reversed by an adenosine A2 receptor antagonist administered
      intraperitoneally. Hence, central NMDA receptor activity can regulate neutrophil
      accumulation in peripheral inflammatory sites by reducing local levels of
      adenosine, an antiinflammatory autacoid which inhibits neutrophil function
      through A2 receptor activation. This represents a previously unknown pathway by
      which the central nervous system influences inflammatory responses.

PMID- 8981926
TI  - The human immunoglobulin V(H) gene repertoire is genetically controlled and
      unaltered by chronic autoimmune stimulation.
AB  - The factors controlling immunoglobulin (Ig) gene repertoire formation are poorly
      understood. Studies on monozygotic twins have helped discern the contributions of
      genetic versus environmental factors on expressed traits. In the present
      experiments, we applied a novel anchored PCR-ELISA system to compare the heavy
      chain V gene (V(H)) subgroup repertoires of mu and gamma expressing B lymphocytes
      from ten pairs of adult monozygotic twins, including eight pairs who are
      concordant or discordant for rheumatoid arthritis. The results disclosed that the
      relative expression of each Ig V(H) gene subgroup is not precisely proportional
      to its relative genomic size. The monozygotic twins had more similar IgM V(H)
      gene repertoires than did unrelated subjects. Moreover, monozygotic twins who are
      discordant for RA also use highly similar IgM V(H) gene-subgroup repertoires.
      Finally, the V(H) gene repertoire remained stable over time. Collectively, these
      data reveal that genetic factors predominantly control V(H) gene repertoire
      formation.

PMID- 8981925
TI  - Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA
      levels, and insulin secretion in HIT-T15 cells.
AB  - FK506 (tacrolimus) is an immunosuppressive drug which interrupts Ca2+-calmodulin
      calcineurin signaling pathways in T lymphocytes, thereby blocking antigen
      activation of T cell early activation genes. Regulation of insulin gene
      expression in the beta cell may also involve Ca2+-signaling pathways and FK506
      has been associated with insulin-requiring diabetes mellitus during clinical use.
      The purpose of this study was to characterize the effects of FK506 on human
      insulin gene transcription, insulin mRNA levels, and insulin secretion using as a
      model the HIT-T15 beta cell line. FK506 had no acute effect on insulin secretion
      in the HIT cell, but caused a reversible time- and dose-dependent (10(-9)-10(-6)
      M) decrease in HIT cell insulin secretion. Decreased insulin secretion in the
      presence of FK506 was also accompanied by a dose-dependent decrease in HIT cell
      insulin content, insulin mRNA levels, and expression of a human insulin promoter
      chloramphenicol acetyl transferase (CAT) reporter gene. FK506 decreased HIT cell
      expression of the human insulin promoter-CAT reporter gene by 40% in the presence
      of both low (0.4 mM) at high (20 mM) glucose concentrations. Western blot
      analysis of HIT cell proteins gave evidence for the presence of calcineurin in
      the HIT cell. These findings suggest that FK506 may have direct effects to
      reversibly inhibit insulin gene transcription, leading to a decline in insulin
      mRNA levels, insulin synthesis, and ultimately insulin secretion.

PMID- 8981927
TI  - Long-lived and transferable tumor immunity in mice after targeted interleukin-2
      therapy.
AB  - A major goal of tumor immunotherapy is the induction of tumor-specific T cell
      responses that are effective in eradicating disseminated tumor, as well as
      mounting a persistent tumor-protective immunity. We demonstrate here that a
      genetically engineered fusion protein consisting of human/mouse chimeric anti
      ganglioside GD2 antibody and human interleukin-2 is able to induce eradication of
      established B78-D14 melanoma metastases in immunocompetent syngeneic C57BL/6J
      mice. This therapeutic effect is mediated by host immune cells, particularly CD8+
      T cells and is associated with the induction of a long-lived immunity preventing
      tumor growth in the majority of animals when challenged up to four months later
      with B78-D14 cells. This effect was tumor-specific, since no cross-protection
      against syngeneic, ganglioside GD2+ EL-4 thymoma cells was observed. Furthermore,
      this tumor-specific protection can be transmitted horizontally to naive,
      syngeneic SCID mice by passive transfer of CD8+ T lymphocytes derived from immune
      animals. These results suggest that antibody-targeted delivery of cytokines
      provides a means to elicit effective immune responses against established tumors
      in the immunotherapy of neoplastic disease.

PMID- 8981928
TI  - Prolonged exposure of human beta cells to elevated glucose levels results in
      sustained cellular activation leading to a loss of glucose regulation.
AB  - Human beta cells can be maintained in serum-free culture at 6 mmol/liter glucose,
      with 80% cell recovery and preserved glucose-inducible functions after 1 wk.
      Between 0 and 10 mmol/liter, glucose dose-dependently increases the number of
      beta cells in active protein synthesis (15% at 0 mmol/liter glucose, 60% at 5
      mmol/liter, and 82% at 10 mmol/liter), while lacking such an effect in islet non
      beta cells (> 75% activated irrespective of glucose concentrations). As in rat
      beta cells, this intercellular difference in glucose sensitivity determines the
      dose-response curves during acute glucose stimulation of human beta cells. During
      2-h incubations, human beta cells synthesize 7 fmol insulin/10(3) cells at 0
      mmol/liter glucose, 20 fmol at 5 mmol/liter, and 31 fmol at 10 mmol/liter.
      Culture at higher (10 or 20 mmol/liter) glucose does not affect beta cell
      recovery but decreases by 50-85% the net effect of glucose upon insulin synthesis
      and release. These reduced responses to glucose are not caused by diminished
      cellular activities but are the consequence of a shift of beta cells to a state
      of sustained activation. The presence of more activated cells at low glucose
      eliminates glucose-dependent cell recruitment as a mechanism for adjusting beta
      cell responses to acute variations in glucose concentration. It leads to elevated
      basal biosynthetic (3-fold) and secretory (10-fold) activities, and, hence, to a
      4-fold reduction in the beta cell insulin content and the amount of insulin
      released at maximal glucose stimulation. Prolonged exposure of human beta cells
      to high glucose can thus lead to a loss of their glucose regulation as a
      consequence of sustained cellular activation, without signs of glucose-induced
      toxicity or desensitization.

PMID- 8981929
TI  - An N-linked high-mannose type oligosaccharide, expressed at the major outer
      membrane protein of Chlamydia trachomatis, mediates attachment and infectivity of
      the microorganism to HeLa cells.
AB  - The structure of the carbohydrate of the 40-kD major outer membrane component of
      Chlamydia trachomatis and its role in defining infectivity of the organism were
      investigated. The oligosaccharides were released from the glycoprotein by N
      glycanase digestion, coupled to a 2-aminopyridyl residue, and subjected to two
      dimensional sugar mapping technique. The major fractions consisted of "high
      mannose type" oligosaccharides containing 8-9 mannose residues. Bi- and tri
      antennary "complex type" oligosaccharides having terminal galactose were detected
      as minor components. These oligosaccharides were N-linked and contained no sialic
      acid. This structural profile is consistent with our previous characterization
      based on lectin-binding and glycosidase digestion. Functional specificity of
      identified chlamydial oligosaccharides was analyzed using glycopeptides
      fractionated from ovalbumin and structurally defined oligosaccharides from other
      sources. The glycopeptide fraction having high-mannose type oligosaccharide, as
      compared to those having complex or hybrid-type, showed a stronger inhibitory
      effect on attachment and infectivity of chlamydial organisms to HeLa cells. Among
      high-mannose type oligosaccharides, the strongest inhibition was observed with
      mannose 8 as compared with mannose 6, 7, or 9. These results indicate that a
      specific high-mannose type oligosaccharide linked to the major outer membrane
      protein of C. trachomatis mediates attachment and infectivity of the organism to
      HeLa cells.

PMID- 8981930
TI  - Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of
      CD16 (FcgammaRIII) and CD11a/CD18 (LFA-1) on NK cells.
AB  - The administration of the immunosuppressive humanized monoclonal antibody CAMPATH
      1-H, which recognizes CD52 on lymphocytes and monocytes, is associated with a
      first-dose cytokine-release syndrome involving TNFalpha, IFNgamma, and IL-6
      clinically. In vitro models have been used to establish the cellular source and
      mechanism responsible for cytokine release, demonstrating that cytokine release
      is isotype dependent, with the rat IgG2b and human IgG1 isotype inducing the
      highest levels of cytokine release, which was inhibited with antibody to CD16,
      the low affinity Fc-receptor for IgG (FcgammaR). Cross-linking antibody opsonized
      CD4 T lymphocytes failed to stimulate TNFalpha release, which together with the
      observation that TNFalpha release by purified natural killer (NK) cells
      stimulated by fixed autologous CAMPATH 1-H-opsonized targets was inhibited with
      anti-CD16, indicates that cytokine release results from ligation of CD16 on the
      NK cells, rather than Fc-receptor (FcR)-dependent cross-linking of CD52 on the
      targeted cell. Since the hierarchy of isotypes inducing cytokine release in these
      cultures matches that seen clinically, we conclude that ligation of CD16 on NK
      cells is also responsible for cytokine release after injection of CAMPATH 1-H in
      vivo.

PMID- 8981931
TI  - Repertoire cloning of lupus anti-DNA autoantibodies.
AB  - To investigate the autoantibody repertoire associated with SLE, we have created
      phage display IgG Fab libraries from two clinically active SLE patients and from
      the healthy identical twin of one of these patients. The libraries from the lupus
      discordant twins were found to both include unusually large representations of
      the V(H)5 gene family. By panning with DNA, the SLE libraries each yielded IgG
      anti-double-stranded (ds) DNA autoantibodies, which are characteristic of lupus
      disease. These included a V(H)5 autoantibody from the affected twin, that has a
      targeted cluster of mutations that potentially improves binding affinity. The
      recovered IgG anti-dsDNA autoantibodies expressed the same idiotypes associated
      with the in vivo IgG anti-dsDNA response of the respective SLE donor. Heavy-light
      chain shuffling experiments demonstrated a case in which the in vitro creation of
      anti-dsDNA binding activity required restrictive pairing of a heavy chain with
      Vlambda light chains similar to those in circulating anti-dsDNA autoantibodies.
      By contrast, IgG anti-ds autoantibodies could not be recovered from the library
      from the healthy twin, or from shuffled libraries with heavy chains from the
      healthy twin. These repertoire analyses illustrate how inheritance and somatic
      processes interplay to produce lupus-associated IgG autoantibodies.

PMID- 8981932
TI  - Congenital hypothyroid goiter with deficient thyroglobulin. Identification of an
      endoplasmic reticulum storage disease with induction of molecular chaperones.
AB  - Recent advances in understanding the molecular pathogenesis of congenital
      hypothyroid goiter in cog/cog mice, have raised important questions concerning
      the maturation of thyroglobulin (the thyroid prohormone) in certain human
      kindreds with congenital goiter. We have now examined affected siblings from two
      unrelated families that synthesize an apparently normally glycosylated, > 300 kD
      immunoreactive thyroglobulin, yet have a reduced quantity of intraglandular
      thyroglobulin and that secreted into the circulation. From thyroid tissues of the
      four patients, light microscopic approaches demonstrated presence of
      intracellular thyroglobulin despite its absence in thyroid follicle lumina, while
      electron microscopy indicated abnormal distention of the endoplasmic reticulum
      (ER). We have confirmed biochemically that most intrathyroidal thyroglobulin
      fails to reach the (Golgi) compartment where complex carbohydrate modification
      takes place. Moreover, the disease in the affected patients is associated with
      massive induction of specific ER molecular chaperones including the hsp90
      homolog, GRP94, and the hsp70 homolog, BiP. The data suggest that these patients
      synthesize a mutant thyroglobulin which is defective for folding/assembly,
      leading to a markedly reduced ability to export the protein from the ER. Thus,
      these kindreds suffer from a thyroid ER storage disease, a cell biological defect
      phenotypically indistinguishable from that found in cog/cog mice.

PMID- 8981933
TI  - Targeted expression of IL-11 in the murine airway causes lymphocytic
      inflammation, bronchial remodeling, and airways obstruction.
AB  - Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in
      response to respiratory viruses, cytokines, and histamine. To further define its
      potential effector functions, the Clara cell 10-kD protein promoter was used to
      express IL-11 and the airways of the resulting transgene mice were characterized.
      In contrast to transgene (-) littermates, the airways of IL-11 transgene (+)
      animals manifest nodular peribronchiolar mononuclear cell infiltrates and
      impressive airways remodeling with subepithelial fibrosis. The inflammatory foci
      contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers
      of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased
      amounts of types III and I collagen, increased numbers of alpha smooth muscle
      actin and desmin-containing cells and a spectrum of stromal elements including
      fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also
      demonstrated that 2-mo-old transgene (+) mice had increased airways resistance
      and non-specific airways hyperresponsiveness to methacholine when compared with
      their transgene (-) littermates. These studies demonstrate that the targeted
      expression of IL-11 in the mouse airway causes a B and T cell-predominant
      inflammatory response, airway remodeling with increased types III and I collagen,
      the local accumulation of fibroblasts, myofibroblasts, and myocytes, and
      obstructive physiologic dysregulation. IL-11 may play an important role in the
      inflammatory and fibrotic responses in viral and/or nonviral human airway
      disorders.

PMID- 8981934
TI  - Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of
      the sphingolipid signaling cascade in cardiac cell death.
AB  - In the present study, it was shown that physiologically relevant levels of the
      proinflammatory cytokine TNFalpha induced apoptosis in rat cardiomyocytes in
      vitro, as quantified by single cell microgel electrophoresis of nuclei ("cardiac
      comets") as well as by morphological and biochemical criteria. It was also shown
      that TNFalpha stimulated production of the endogenous second messenger,
      sphingosine, suggesting sphingolipid involvement in TNFalpha-mediated
      cardiomyocyte apoptosis. Consistent with this hypothesis, sphingosine strongly
      induced cardiomyocyte apoptosis. The ability of the appropriate stimulus to drive
      cardiomyocytes into apoptosis indicated that these cells were primed for
      apoptosis and were susceptible to clinically relevant apoptotic triggers, such as
      TNFalpha. These findings suggest that the elevated TNFalpha levels seen in a
      variety of clinical conditions, including sepsis and ischemic myocardial
      disorders, may contribute to TNFalpha-induced cardiac cell death. Cardiomyocyte
      apoptosis is also discussed in terms of its potential beneficial role in limiting
      the area of cardiac cell involvement as a consequence of myocardial infarction,
      viral infection, and primary cardiac tumors.

PMID- 8981935
TI  - Functional analysis of the mutations in the human cardiac beta-myosin that are
      responsible for familial hypertrophic cardiomyopathy. Implication for the
      clinical outcome.
AB  - More than 30 missense mutations in the beta-cardiac myosin heavy chain gene have
      been shown to be responsible for familial hypertrophic cardiomyopathy. To clarify
      the effects of these point mutations on myosin motor function, we expressed wild
      type and mutant human beta-cardiac myosin heavy chains in insect cells with human
      cardiac light chains. The wild-type myosin was well purified with similar
      enzymatic and motor activities to those of the naturally isolated V3 cardiac
      myosin. Arg249-->Gln and Arg453-->Cys mutations resulted in decreased actin
      translocating activity (61 and 23% of the wild-type, respectively) with decreased
      intrinsic ATPase activity. Arg403-->Gln mutation greatly decreased actin
      translocating activity (27% of wild type) with a 3.3-fold increased dissociation
      constant for actin, while intrinsic ATPase activity was unchanged. Val606-->Met
      mutation only mildly affected the actin translocating activity as well as ATPase
      activity of myosin. The degree of deterioration by each mutation was closely
      correlated with the prognosis of the affected kindreds, indicating that myosin
      dysfunction caused by the point mutations is responsible for the pathogenesis of
      the disease. Structure/function relationship of myosin is discussed.

PMID- 8981936
TI  - Local anesthetics as effectors of allosteric gating. Lidocaine effects on
      inactivation-deficient rat skeletal muscle Na channels.
AB  - Time- and voltage-dependent local anesthetic effects on sodium (Na) currents are
      generally interpreted using modulated receptor models that require formation of
      drug-associated nonconducting states with high affinity for the inactivated
      channel. The availability of inactivation-deficient Na channels has enabled us to
      test this traditional view of the drug-channel interaction. Rat skeletal muscle
      Na channels were mutated in the III-IV linker to disable fast inactivation
      (F1304Q: FQ). Lidocaine accelerated the decay of whole-cell FQ currents in
      Xenopus oocytes, reestablishing the wild-type phenotype; peak inward current at 
      20 mV was blocked with an IC50 of 513 microM, while plateau current was blocked
      with an IC50 of only 74 microM (P < 0.005 vs. peak). In single-channel
      experiments, mean open time was unaltered and unitary current was only reduced at
      higher drug concentrations, suggesting that open-channel block does not explain
      the effect of lidocaine on FQ plateau current. We considered a simple model in
      which lidocaine reduced the free energy for inactivation, causing altered
      coupling between activation and inactivation. This model readily simulated
      macroscopic Na current kinetics over a range of lidocaine concentrations.
      Traditional modulated receptor models which did not modify coupling between
      gating processes could not reproduce the effects of lidocaine with rate constants
      constrained by single-channel data. Our results support a reinterpretation of
      local anesthetic action whereby lidocaine functions as an allosteric effector to
      enhance Na channel inactivation.

PMID- 8981938
TI  - Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs
      enhances wound repair in rat skin.
AB  - Based on preliminary but variable results with direct DNA transfer into wounds,
      we evaluated in vivo gene transfer by particle-mediated DNA delivery to rat skin
      to determine whether overexpression of TGF-beta1 at the site of skin incisions
      would result in a significant improvement in repair. Optimization of the method
      with viral promoter-luciferase reporter constructs indicated that expression of
      luciferase activity persisted up to 5 d and was promoter, pressure, and site
      dependent (ventral > dorsal). Using cytomegalovirus (CMV)-driven human alpha1
      antitrypsin, transgene expression was immunolocalized within keratinocytes of the
      stratum granulosum at 24 h. We measured tensile strength of skin incisions at 11
      21 d in both normal and diabetic rats transfected with TGF-beta1 expression
      vectors at surgery. Native murine TGF-beta1 under an SV40 promoter produced
      positive effects, while wound strengthening was more pronounced in diabetic
      animals using a CMV-driven construct. Transfection of rat skin with
      constitutively active, mutant porcine TGF-beta1 under the control of the CMV and
      Moloney murine leukemia virus promoters significantly increased tensile strength
      up to 80% for 14-21 d after surgery. Transfection 24 h before surgery was more
      effective. Particle-mediated gene delivery can be used to deliver viral promoter
      cytokine expression constructs into rat skin in a safe, efficient, and
      reproducible fashion. The extent of wound repair, as evidenced by enhanced
      tensile strength, can be markedly improved in tissues transfected with TGF-beta1
      expression constructs.

PMID- 8981939
TI  - 1996 ASHG Presidential Address. Toward the 21st century.

PMID- 8981937
TI  - Increased expression of insulin/insulin-like growth factor-I hybrid receptors in
      skeletal muscle of noninsulin-dependent diabetes mellitus subjects.
AB  - Insulin receptors (IR) and IGF-I receptors (IGF-IR) have been shown to form
      hybrid receptors in tissues coexpressing both molecules. To date there is no
      information about the distribution of hybrids in tissues of normal or diabetic
      subjects. We developed a microwell-based immunoassay to quantitate hybrids in
      small human tissues samples. Microwells were coated with MA-20 anti-IR antibody
      or alpha-IGF-IR-PA antibody directed against the IGF-IR alpha-subunit, and
      incubated with skeletal muscle extracts of patients with noninsulin-dependent
      diabetes mellitus (NIDDM) and normal controls. Immobilized receptors were
      incubated with 125I-insulin or 125I-IGF-I in the presence or absence of the two
      unlabeled ligands. Hybrids were quantified as the fraction of 125I-IGF-I binding
      immunoadsorbed with MA-20 and expressed as percentage of total IGF-IR (type
      I+hybrids) immobilized with alpha-IGF-IR-PA. The immunoassay was validated using
      Western blotting analysis. Relative abundance of hybrids detected in NIDDM
      patients was higher than in controls. The percentage of hybrids was negatively
      correlated with IR number and in vivo insulin sensitivity measured by an insulin
      tolerance test, whereas the percentage was positively correlated with
      insulinemia. Insulin binding affinity was lower in NIDDM patients than in
      controls, and was correlated with the percentage of hybrids. Maximal IGF-I
      binding was significantly higher in muscle from NIDDM patients compared to
      controls and was positively correlated with the percentage of hybrid receptors
      whereas IGF-I binding affinity did not differ between the two groups. These
      results raise the possibility that alterations in expression of hybrid receptors
      may contribute to decreased insulin sensitivity, and to increased sensitivity to
      IGF-I. Because IGF-I has been proposed as a hypoglycemic agent in NIDDM, these
      results are relevant to the development of new approaches to the treatment of
      insulin resistance of NIDDM.

PMID- 8981940
TI  - Variable expressivity of patched mutations in flies and humans.

PMID- 8981941
TI  - Using genetics to dissect cognition.

PMID- 8981942
TI  - Empirical evidence that genetic counseling is directive: where do we go from
      here?

PMID- 8981943
TI  - Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a
      premature termination of the PATCHED protein, and no genotype-phenotype
      correlations are evident.
AB  - The human homologue of the Drosophila segment polarity gene patched is implicated
      in the development of nevoid basal cell carcinoma syndrome (NBCCS) and in the
      genesis of sporadic basal cell carcinomas. In order to examine the phenotypic
      variability in NBCCS and to highlight functionally important domains of the PTCH
      protein, we have now screened 71 unrelated NBCCS individuals for mutations in the
      PTCH exons. We identified 28 mutations that are distributed throughout the entire
      gene, and most (86%) cause protein truncation. As part of this analysis, we
      demonstrate that failure of one NBCCS family to show clear linkage to chromosome
      9q22.3-31 is most likely due to germinal mosaicism. We have identified three
      families bearing identical mutations with variable phenotypes, suggesting
      phenotypic variability in NBCCS is a complex genetic event. No phenotype genotype
      correlation between the position of truncation mutations and major clinical
      features was evident. Two missense mutations have been identified, and their
      location within transmembrane domains supports the notion that PTCH may have a
      transport function. The preponderance of truncation mutants in the germ line of
      NBCCS patients suggests that the developmental defects associated with the
      disorder are most likely due to haploinsufficiency.

PMID- 8981944
TI  - Susceptibility loci for distinct components of developmental dyslexia on
      chromosomes 6 and 15.
AB  - Six extended dyslexic families with at least four affected individuals were
      genotyped with markers in three chromosomal regions: 6p23-p21.3, 15pter-qter, and
      16pter-qter. Five theoretically derived phenotypes were used in the linkage
      analyses: (1) phonological awareness; (2) phonological decoding; (3) rapid
      automatized naming; (4) single-word reading; and (5) discrepancy between
      intelligence and reading performance, an empirically derived, commonly used
      phenotype. Two-point and multipoint allele-sharing analyses of chromosome 6
      markers revealed significant evidence (P < 10(-6)) for linkage of the
      phonological awareness phenotype to five adjacent markers (D6S109, D6S461,
      D6S299, D6S464, and D6S306). The least compelling results were obtained with
      single-word reading. In contrast, with chromosome 15 markers, a LOD score of 3.15
      was obtained for marker D15S143 at theta = 0.0 with single-word reading.
      Multipoint analyses with markers adjacent to D15S143 (D15S126, D15S132, D15S214,
      and D15S128) were positive, but none reached acceptable significance levels.
      Chromosome 15 analyses with the phonological awareness phenotype were negative.
      Parametric and nonparametric linkage analyses with chromosome 16 markers were
      negative. The most intriguing aspect of the current findings is that two very
      distinct reading-related phenotypes, reflecting different levels in the hierarchy
      of reading-related skills, each contributing to different processes, appear to be
      linked to two different chromosomal regions.

PMID- 8981945
TI  - Nondirectiveness in genetic counseling: an empirical study.
AB  - Nondirectiveness is considered an essential part of genetic counseling, yet there
      is no generally accepted definition nor data documenting its impact on
      counselees. This study is an empirical investigation of directiveness, using
      ratings from transcripts of consultations and comparing these with counselor
      reported and counselee-reported directiveness. Rated directiveness was defined as
      advice, expressed views about or selective reinforcement of counselees' behavior,
      thoughts, or emotions (advice, evaluation, and reinforcement). Analysis of 131
      transcripts revealed a mean of 5.8 advice statements per consultation, 5.8
      evaluative statements, and 1.7 reinforcing statements. When asked to describe
      their counseling style, none of the 11 counselors rated it as "not at all"
      directive. Half the counselees who faced a decision felt steered by the
      counselor. Items of rated directiveness showed satisfactory interrater
      reliability (kappa = .63). Factor analysis revealed that they formed one factor
      (eigenvalue 1.72). There were no associations either between counselor-reported,
      counselee-reported, and rated directiveness or between these measures and
      counselee anxiety and concern, satisfaction with information, or the meeting of
      counselees' expectations. Rated directiveness was the only measure to be
      associated with other process measures of the consultation, being associated with
      longer consultations, more blocks of speech, more social and emotional issues
      being raised, and fewer concerns being followed up. Advice was more likely to be
      given to counselees of lower socioeconomic status and to counselees judged by
      counselors to be highly concerned. Evaluative statements were more likely to be
      made by counselors who had received counseling training. These results show that
      genetic counseling was not characterized--by counselors, counselees, or a
      standardized rating scale--as uniformly nondirective.

PMID- 8981946
TI  - Duplication of seven exons in the lysyl hydroxylase gene is associated with
      longer forms of a repetitive sequence within the gene and is a common cause for
      the type VI variant of Ehlers-Danlos syndrome.
AB  - The type VI variant of the Ehlers-Danlos syndrome (EDS) is a recessively
      inherited connective tissue disorder which, in most families, is due to a
      deficiency in lysyl hydroxylase activity. We have recently characterized a
      homozygous duplication of 8.9 kb in the lysyl hydroxylase gene (PLOD) in two EDS
      VI families. The duplication is caused by a homologous recombination of Alu
      sequences in introns 9 and 16. Using PCR, we have analyzed 26 additional EDS VI
      families from various countries and found that 7 of them have this duplication.
      Our data has shown a frequency of 19.1% for this mutant allele among 35 EDS VI
      families studied by us so far. Our haplotype analysis shows a variation in the
      sequence of DNA region surrounding the duplication. There is an association
      between a particular allele size class, the long form, at the dinucleotide repeat
      within intron 16 and the duplication mutation in PLOD. Screening of a general
      population revealed one positive finding among 582 alleles tested. An abnormal
      sequence in exon 17 of the gene, which generated a stop codon in the exon
      sequence and aberrant mRNA processing, was responsible for the nonfunctionality
      of the other allele in one of the compound heterozygous patients.

PMID- 8981947
TI  - Autosomal recessive Sorsby fundus dystrophy revisited: molecular evidence for
      dominant inheritance.
AB  - Sorsby fundus dystrophy (SFD) originally was characterized as an autosomal
      dominant disorder in which patients lose central vision during the 4th or 5th
      decade of life. Since Sorsby's initial description, interfamilial phenotypic
      variations have been noted and have given rise to controversy as to whether SFD
      constitutes more than one nosologic entity. In addition, several reports have
      proposed the existence of a recessively inherited form of SFD. The recent
      identification of the tissue inhibitor of metalloproteinases-3 (TIMP3) as the
      disease-causing gene in SFD has made it possible to address the questions of
      clinical and genetic heterogeneity. In this study, we reinvestigated a large,
      highly consanguineous Finnish family previously diagnosed as having early-onset
      autosomal recessive SFD. We identified a novel heterozygous Gly166Cys mutation in
      TIMP3 in all affected individuals and provide strong evidence for an autosomal
      dominant inheritance of the SFD phenotype in this family. Our results, in
      conjunction with a critical review of the reported cases, render the existence of
      a recessive mode of inheritance in SFD questionable. Considering all available
      data, we suggest that SFD is a genetically homogeneous, autosomal dominant
      condition.

PMID- 8981948
TI  - Identification of point mutations in 41 unrelated patients affected with Menkes
      disease.
AB  - Genomic DNA of 41 unrelated patients affected with the classical severe form of
      Menkes disease was investigated for point mutations in the ATP7A gene (previously
      designated as the "MNK" gene). Using SSCP analysis and direct sequencing of the
      exons amplified by PCR, we identified 41 different mutations, including 19
      insertions/deletions, 10 nonsense mutations, 4 missense mutations, and 8 splice
      site alterations. Approximately 90% of the mutations were predicted to result in
      the truncation of the protein (ATP7A). In 20 patients the mutations were within
      exons 7-10, and half of these mutations affected exon 8. Furthermore, five
      alterations were observed within the 6-bp sequence at the splice-donor site of
      intron 8, which would be predicted to affect the efficiency of splicing of exon
      8. Although a specific function has not been attributed to the protein region
      encoded by this exon, this region may be important in serving as a "stalk"
      joining the metal-binding domains and the ATPase core. The present findings not
      only help us in understanding the underlying genetic defect but are invaluable
      data especially for carrier detection and prenatal diagnosis of this lethal
      disorder.

PMID- 8981949
TI  - The gene encoding p44, a subunit of the transcription factor TFIIH, is involved
      in large-scale deletions associated with Werdnig-Hoffmann disease.
AB  - Mutations of the survival motor neurone gene (SMN) are associated with spinal
      muscular atrophy (SMA), a frequent lethal autosomal recessive disorder. In spite
      of this, no phenotype-genotype correlation was observed, since the SMN gene is
      lacking in the majority of patients affected with either the severe form (type I)
      or the milder forms (types II and III). Here, we show that the gene encoding p44,
      a subunit of the basal transcription factor TFIIH, is duplicated in the SMA
      region and that the p44 gene products (p44t and p44c) differ by three amino acid
      changes. Gene analysis of a total of 94 unrelated SMA patients revealed that the
      p44t gene is involved in large-scale deletions associated with Werdnig-Hoffmann
      disease (type I). The TFIIH polypeptide composition as well as transcription and
      DNA repair activities are normal in patients lacking the p44t gene on both mutant
      chromosomes, suggesting that the p44t gene is not critical for the development of
      SMA.

PMID- 8981950
TI  - Hereditary multiple exostoses (EXT): mutational studies of familial EXT1 cases
      and EXT-associated malignancies.
AB  - Hereditary multiple exostoses (EXT) is an autosomal dominant disorder
      characterized by the formation of cartilage-capped prominences that develop from
      the growth centers of the long bones. EXT is genetically heterogeneous, with
      three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1
      gene, located on chromosome 8q24.1, has been cloned and is encoded by a 3.4-kb
      cDNA. Five mutations in the EXT1 gene have been identified--four germ-line
      mutations, including two unrelated families with the same mutation, and one
      somatic mutation in a patient with chondrosarcoma. Four of the mutations
      identified resulted in frameshifts and premature termination codons, while the
      fifth mutation resulted in a substitution of leucine for arginine. Loss of
      heterozygosity (LOH) analysis of chondrosarcomas and chondroblastomas revealed
      multiple LOH events at loci on chromosomes 3q, 8q, 10q, and 19q. One sporadic
      chondrosarcoma demonstrated LOH for EXT1 and EXT3, while a second underwent LOH
      for EXT2 and chromosome 10. A third chondrosarcoma underwent LOH for EXT1 and
      chromosome 3q. These results agree with previous findings that mutations at EXT1
      and multiple genetic events that include LOH at other loci may be required for
      the development of chondrosarcoma.

PMID- 8981951
TI  - The molecular basis of partial penetrance of splicing mutations in cystic
      fibrosis.
AB  - The splicing variant, 5T allele, in intron 8 of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene was shown to be associated with partial
      penetrance of the clinical expression. This splicing variant leads to two
      possible transcripts: one normal and the other aberrantly spliced that lacks exon
      9. The aim of this study was to analyze the molecular basis of the partial
      penetrance in individuals carrying the 5T allele. We analyzed the level of the
      correctly spliced RNA transcribed from the 5T allele in nasal and epididymal
      epithelium and correlated it with disease expression. Semiquantitative
      nondifferential reverse-transcriptase-PCR showed a considerable variability (6%
      37%) in the total level of correctly spliced RNA transcribed from the 5T allele
      in nasal epithelium from 11 patients. A significant nonlinear correlation (r =
      .82, P = .002) between the level of the normal CFTR transcripts and the severity
      of lung disease was shown. No individuals with normal lung function and minimal
      or no lung disease (FEV1 >80% predicted) had <25% of normal transcripts, and
      individuals with <15% of normal transcripts did not have FEV1 >80%. The level of
      normal transcripts in epididymal epithelial cells from four infertile males with
      congenital bilateral absence of the vas deferens was low (6%-24%). In infertile
      males with normal lung function the level of correctly spliced transcripts in the
      nasal epithelium was higher than the level in the epididymal epithelium. These
      results indicate that there is variability in the efficiency of the splicing
      mechanism, among different individuals and between different organs of the same
      individual. This variability provides the molecular basis of the partial
      penetrance of cystic fibrosis disease in patients carrying the 5T allele.

PMID- 8981952
TI  - Analysis of the phenylalanine hydroxylase gene in the Spanish population:
      mutation profile and association with intragenic polymorphic markers.
AB  - The aim of this study was to characterize the phenylketonuria (PKU) alleles in
      the Spanish population, by both identifying the causative mutations and analyzing
      the RFLP haplotypes and the VNTR and short-tandem-repeat alleles associated with
      the phenylalanine hydroxylase (PAH) gene. We have investigated 129 independent
      mutant chromosomes, using denaturing gradient gel electrophoresis (DGGE) and
      direct sequencing. Ninety percent of the alleles were identified, and a total of
      40 different mutations were detected. The mutational spectrum includes seven
      previously unreported mutations: P122Q, D129G, P147S, D151G, A165T, S196fs, and
      P407S. Seven mutations represent 43% of the Spanish PKU alleles, the most common
      being IVS10nt-11g-->a (14.7%), I65T (8.5%), and V388M (6.2%). The remaining 33
      mutations are rare. The mutation profile and relative frequencies are markedly
      different from those in northern Europe, also showing unique features compared
      with those in other, southern European populations. The association analysis with
      polymorphic markers in the PAH gene provides valuable information for population
      genetic studies and investigation of the origins of the mutations. This study may
      serve as reference in the analysis of the contemporary distributions and
      frequencies of the PKU mutations in related populations, with particular
      relevance in Latin American countries.

PMID- 8981953
TI  - Predisposition to the fragile X syndrome in Jews of Tunisian descent is due to
      the absence of AGG interruptions on a rare Mediterranean haplotype.
AB  - We have studied the ethnic distribution of the fragile X syndrome in Israel and
      have found that 36/136 (26.5%) of apparently unrelated pedigrees were of Tunisian
      Jewish descent. The Tunisian Jews, however, constitute only 2%-3% of the general
      Israeli population, identifying the first ethnic group significantly (P < .001)
      predisposed to the development of this disease. Associated with this increase in
      disease prevalence, we have found an unusually high incidence of FMR1 CGG repeats
      devoid of AGG interruptions among the normal Tunisian Jewish population (30/150,
      or 20.0%). Furthermore, the proportion of these alleles beyond the FMR1 CGG
      repeat instability threshold (>35 repeats) (8/150, or 5.3%) was significantly
      greater (P < .04) than that proportion found among non-Tunisian Jewish controls
      in Israel (1/136). Haplotype analysis has indicated that these large
      uninterrupted CGG repeat alleles are present on a previously unreported (DXS548
      FRAXAC1-FRAXAC2) haplotype that accounts for all observed cases of disease among
      Tunisian Jewish X chromosomes. The high prevalence of disease among Tunisian
      Jews, we suggest, is due to a founder effect of this rare haplotype, which is
      completely devoid of AGG interruptions in the Jewish population of Tunisia.

PMID- 8981954
TI  - Molecular characterization of a 130-kb terminal microdeletion at 22q in a child
      with mild mental retardation.
AB  - We have analyzed a recently described 22q13.3 microdeletion in a child with some
      overlapping features of the cytologically visible 22q13.3 deletion syndrome.
      Patient NT, who shows mild mental retardation and delay of expressive speech, was
      previously found to have a paternal microdeletion in the subtelomeric region of
      22q. In order to characterize this abnormality further, we have constructed a
      cosmid/P1 contig covering the terminal 150 kb of 22q, which encompasses the 130
      kb microdeletion. The microdeletion breakpoint is within the VNTR locus D22S163.
      The cloning of the breakpoint sequence revealed that the broken chromosome end
      was healed by the addition of telomeric repeats, indicating that the
      microdeletion is terminal. This is the first cloned terminal deletion breakpoint
      on a human chromosome other than 16p. The cosmid/P1 contig was mapped by pulsed
      field gel electrophoresis analysis to within 120 kb of the arylsulfatase A gene,
      which places the contig in relation to genetic and physical maps of the
      chromosome. The acrosin gene maps within the microdeletion, approximately 70 kb
      from the telomere. With the distal end of chromosome 22q cloned, it is now
      possible to isolate genes that may be involved in the overlapping phenotype of
      this microdeletion and 22q13.3 deletion syndrome.

PMID- 8981956
TI  - Fine mapping of the nail-patella syndrome locus at 9q34.
AB  - Nail-patella syndrome (NPS), or onychoosteodysplasia, is an autosomal dominant,
      pleiotropic disorder characterized by nail dysplasia, absent or hypoplastic
      patellae, iliac horns, and nephropathy. Previous studies have demonstrated
      linkage of the nail-patella locus to the ABO and adenylate kinase loci on human
      chromosome 9q34. As a first step toward isolating the NPS gene, we present
      linkage analysis with 13 polymorphic markers in five families with a total of 69
      affected persons. Two-point linkage analysis with the program MLINK showed tight
      linkage of NPS and the anonymous markers D9S112 (LOD = 27.0; theta = .00) and
      D9S315 (LOD = 22.0; theta = .00). Informative recombination events place the NPS
      locus within a 1-2-cM interval between D9S60 and the adenylate kinase gene (AK1).

PMID- 8981957
TI  - Genetic and environmental architecture of the features of the insulin-resistance
      syndrome.
AB  - The contribution of genetic and environmental effects to the clustering of
      metabolic factors contained in insulin-resistance syndrome (IRS) is still
      unclear. To explore the genetic architecture of IRS, we examined a population of
      elderly twins from the Swedish Adoption/Twin Study of Aging. A sample of 289
      pairs of twins (mean age 65.5 years; range 52-86 years), of whom 140 pairs had
      been reared apart, was studied. The features contained in the IRS consisted of
      body-mass index (BMI), insulin resistance, triglycerides, HDL cholesterol, and
      systolic blood pressure. Intraclass correlations, cross-twin correlations, and
      model-fitting analyses were used to evaluate the relative importance of genetic
      and environmental influences for variation in and covariation among the
      components of the syndrome. All of the five principal metabolic components
      contained in IRS are more or less influenced by a single latent genetic factor,
      whereas only three of the components (triglycerides, insulin resistance, and HDL
      cholesterol) are influenced by a latent individual-specific environmental factor.
      The genetic factor reflected influences of importance to BMI and insulin
      resistance and to a lesser degree to triglycerides, HDL cholesterol, and systolic
      blood pressure, whereas the individual-specific environmental factor reflected
      influences in common to triglycerides and HDL cholesterol and to a lesser degree
      to insulin resistance. Systolic blood pressure was related to IRS, albeit weakly,
      only through genetic effects. In conclusion, IRS appears to be influenced by
      different sets of genetic and environmental mechanisms. The set of genetic
      influences in common to all the components may initiate the abnormalities
      underlying IRS.

PMID- 8981958
TI  - mtDNA analysis shows common ancestry in two kindreds with X-linked recessive
      hypoparathyroidism and reveals a heteroplasmic silent mutation.
AB  - Two kindreds residing in eastern Missouri and exhibiting X-linked recessive
      idiopathic hypoparathyroidism have been described. Genealogical records extending
      back five generations revealed no common ancestor. To investigate the possibility
      of relatedness, the DNA sequence of the mitochondrial D-loop was compared among
      several individuals in both kindreds. The mtDNA D-loop was amplified from the
      total DNA of individuals by use of nested PCR reactions, and the resulting 430-bp
      fragment was sequenced. The mtDNA sequence was identical among affected males and
      their maternal lineage for individuals in both kindreds. Conversely, the mtDNA
      sequence of the fathers of the affected males differed from that of the maternal
      lineage at three to six positions. These results demonstrate that the two
      kindreds exhibiting X-linked recessive hypoparathyroidism are indeed related and
      that an identical gene defect is responsible for the disease. A further feature
      of the inheritance pattern was examined when a unique point mutation was
      identified in the mtDNA of one branch of one of the kindreds. This mutation
      appears to be de novo and segregates in subsequent generations without obscuring
      relatedness. In addition, the results of our study of mtDNA analysis indicate
      that this approach may be of importance in investigating common ancestry in other
      X-linked disorders.

PMID- 8981955
TI  - Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on
      chromosome 11q23.
AB  - Hereditary nonchromaffin paragangliomas (PGL; glomus tumors; MIM 168000) are
      mostly benign, slow-growing tumors of the head and neck region, inherited from
      carrier fathers in an autosomal dominant fashion subject to genomic imprinting.
      Genetic linkage analysis in two large, unrelated Dutch families assigned PGL loci
      to two regions of chromosome 11, at 11q23 (PGL1) and 11q13.1 (PGL2). We
      ascertained a total of 11 North American PGL families and confirmed maternal
      imprinting (inactivation). In three of six families, linkage analysis provided
      evidence of linkage to the PGL1 locus at 11q23. Recombinants narrowed the
      critical region to an approximately 4.5-Mb interval flanked by markers D11S1647
      and D11S622. Partial allelic loss of strictly maternal origin was detected in 5
      of 19 tumors. The greatest degree of imbalance was detected at 11q23, distal to
      D11S1327 and proximal to CD3D. Age at onset of symptoms was significantly
      different between fathers and children (Wilcoxon rank-sum test, P < .002).
      Affected children had an earlier age at onset of symptoms in 39 of 57 father
      child pairs (chi2 = 7.74, P < .006). However, a more conservative comparison of
      the number of pairs in which a child had > or = 5 years earlier age at onset (n =
      33) vis-a-vis that of complementary pairs (n = 24) revealed no significant
      difference (chi2 = 1.42, P > .2). Whether these data represent genetic
      anticipation or ascertainment bias can be addressed only by analysis of a larger
      number of father-child pairs.

PMID- 8981959
TI  - Uniparental disomy of the entire X chromosome in a female with Duchenne muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a severe, progressive, X-linked muscle
      wasting disorder with an incidence of approximately 1/3,500 male births. Females
      are also affected, in rare instances. The manifestation of mild to severe
      symptoms in female carriers of dystrophin mutations is often the result of the
      preferential inactivation of the X chromosome carrying the normal dystrophin
      gene. The severity of the symptoms is dependent on the proportion of cells that
      have inactivated the normal X chromosome. A skewed pattern of X inactivation is
      also responsible for the clinical manifestation of DMD in females carrying
      X;autosome translocations, which disrupt the dystrophin gene. DMD may also be
      observed in females with Turner syndrome (45,X), if the remaining X chromosome
      carries a DMD mutation. We report here the case of a karyotypically normal female
      affected with DMD as a result of homozygosity for a deletion of exon 50 of the
      dystrophin gene. PCR analysis of microsatellite markers spanning the length of
      the X chromosome demonstrated that homozygosity for the dystrophin gene mutation
      was caused by maternal isodisomy for the entire X chromosome. This finding
      demonstrates that uniparental isodisomy of the X chromosome is an additional
      mechanism for the expression of X-linked recessive disorders. The proband's
      clinical presentation is consistent with the absence of imprinted genes (i.e.,
      genes that are selectively expressed based on the parent of origin) on the X
      chromosome.

PMID- 8981962
TI  - Mapping genes underlying ethnic differences in disease risk by linkage
      disequilibrium in recently admixed populations.
AB  - Where recent admixture has occurred between two populations that have different
      disease rates for genetic reasons, family-based association studies can be used
      to map the genes underlying these differences, if the ancestry of the alleles at
      each locus examined can be assigned to one of the two founding populations. This
      article explores the statistical power and design requirements of this approach.
      Markers suitable for assigning the ancestry of genomic regions could be defined
      by grouping alleles at closely spaced microsatellite loci into haplotypes, or
      generated by representational difference analysis. For a given relative risk
      between populations, the sample size required to detect a disease locus that
      accounts for this relative risk by linkage-disequilibrium mapping in an admixed
      population is not critically dependent on assumptions about genotype penetrances
      or allele frequencies. Using the transmission-disequilibrium test to search the
      genome for a locus that accounts for a relative risk of between 2 and 3 in a high
      risk population, compared with a low-risk population, generally requires between
      150 and 800 case-parent pairs of mixed descent. The optimal strategy is to
      conduct an initial study using markers spaced at < or = 10 cM with cases from the
      second and third generations of mixed descent, and then to map the disease loci
      more accurately in a subsequent study of a population with a longer history of
      admixture. This approach has greater statistical power than allele-sharing
      designs and has obvious applications to the genetics of hypertension, non-insulin
      dependent diabetes, and obesity.

PMID- 8981960
TI  - Genomewide search for genes influencing percent body fat in Pima Indians:
      suggestive linkage at chromosome 11q21-q22. Pima Diabetes Gene Group.
AB  - On the basis of accumulating evidence that obesity has a substantial genetic
      component, a genomewide search for linkages of DNA markers to percent body fat is
      ongoing in Pima Indians, a population with a very high prevalence of obesity. An
      initial screen of the genome (>600 markers in 874 individuals) has been completed
      using highly polymorphic markers (mean heterozygosity = .67). Reported here are
      the sib-pair linkage results for percent body fat (277 siblings), the best
      available indicator of overall obesity. Single-marker linkages to percent body
      fat were evaluated by sib-pair analysis for quantitative traits. From these
      analyses, the best evidence of genes influencing body fat came from markers at
      chromosome 11q21-q22 and 3p24.2-p22 (P = .001; LOD = 2.0). Regions flanking these
      markers were further investigated by multipoint linkage. The evidence for linkage
      at 11q21-q22 increased to P = .0002 (LOD = 2.8), peaking between markers D11S2000
      and D11S2366. Evidence for linkage at 3p24.2-p22 did not change. No association
      was detected for any marker in the region. Although several genes are known in
      the 11q21-q22 region, none have been implicated as candidate genes for obesity.

PMID- 8981963
TI  - Allelic disequilibrium and allele frequency distribution as a function of social
      and demographic history.
AB  - Allelic disequilibrium between closely linked genes is a common observation in
      human populations and often gives rise to speculation concerning the role of
      selective forces. In a previous treatment, we have developed a population model
      of the expected distribution of rare variants (including private polymorphisms)
      in Amerindians and have argued that, because of the great expansion of Amerindian
      numbers with the advent of agriculture, most of these rare variants are of
      relatively recent origin. Many other populations have similar histories of
      striking recent expansions. In this treatment, we demonstrate that, in
      consequence of this fact, a high degree of linkage disequilibrium between two
      nonhomologous alleles <0.5 cM apart is the "normal" expectation, even in the
      absence of selection. This expectation is enhanced by the previous subdivision of
      human populations into relatively isolated tribes characterized by a high level
      of endogamy and inbreeding. We also demonstrate that the alleles associated with
      a recessive disease phenotype are expected to exist in a population in very
      variable frequencies: there is no need to postulate positive selection with
      respect to the more common disease-associated alleles for such entities as
      phenylketonuria or cystic fibrosis.

PMID- 8981961
TI  - Evidence of a non-MHC susceptibility locus in type I diabetes linked to HLA on
      chromosome 6.
AB  - Linkage studies have led to the identification of several chromosome regions that
      may contain susceptibility loci to type I diabetes (IDDM), in addition to the HLA
      and INS loci. These include two on chromosome 6q, denoted IDDM5 and IDDM8, that
      are not linked to HLA. In a previous study, we noticed that the evidence for
      linkage to IDDM susceptibility around the HLA locus extended over a total
      distance of 100 cM, which suggested to us that another susceptibility locus could
      reside near HLA. We developed a statistical method to test this hypothesis in a
      panel of 523 multiplex families from France, the United States, and Denmark (a
      total of 667 affected sib pairs, 536 with both parents genotyped), and here
      present evidence (P = .00003) of a susceptibility locus for IDDM located 32 cM
      from HLA in males but not linked to HLA in females and distinct from IDDM5 and
      IDDM8. A new statistical method to test for the presence of a second
      susceptibility locus linked to a known first susceptibility locus (here HLA) is
      presented. In addition, we analyzed our current family panel with markers for
      IDDM5 and IDDM8 on chromosome 6 and found suggestions of linkage for both of
      these loci (P = .002 and .004, respectively, on the complete family panel). When
      cumulated with previously published results, with overlapping families removed,
      the affected-sib-pair tests had a significance of P = .0001 for IDDM5 and P =
      .00004 for IDDM8.

PMID- 8981964
TI  - Insurance underwriting in the genetic era.
AB  - Genetic technology is assuming a greater role in the practice of medicine.
      Insurers have a vested interest because individually underwritten insurance
      cannot be sold without risk classification, and much of the medical information
      needed to classify risks will have a genetic component. This paper reviews recent
      genetic advances and their potential impact on life, disability income, long-term
      care, and critical illness insurance. Alzheimer disease is chosen to illustrate
      the effect of an organized effort to withhold medical information from insurance
      companies. Consumers will not support a private insurance mechanism with
      extensive cross-subsidization among policyholders and where medical information
      becomes inviolate simply because it is genetic. A framework for deliberations
      with the medical community is proposed.

PMID- 8981965
TI  - Magnitude of type I error when single-locus linkage analysis is maximized over
      models: a simulation study.
AB  - It is well known that maximizing the maximum LOD score over multiple parameter
      values or models (i.e., the method of mod scores, or MMLS), will inflate type I
      error, compared with assuming only one parameter value/model in the linkage
      analysis. On the other hand, a mod score often has greater power to detect
      linkage than does a LOD score (Z) calculated under a wrong genetic model.
      Therefore, it is of interest to determine the actual magnitude of type I error in
      realistic genetic situations. Simulated data sets with no linkage were generated
      under three dominant and three recessive single-locus models, with reduced
      penetrance (f = .8, .5, and .2). Data sets were analyzed for linkage by (1)
      maximizing over penetrance only, (2) maximizing over "dominance model" (i.e.,
      dominant versus recessive), and (3) maximizing over both penetrance and dominance
      model simultaneously. In (1), the resultant significance levels were
      approximately doubled, compared with baseline values if one had not maximized
      over penetrances (i.e., compared with a one-sided chi2(1)). In (2), significance
      levels were increased somewhat less, and, in (3), they were increased by
      approximately two to three times (but not more than four times) over those of the
      one-sided chi2(1). This means that, for a given size of test alpha, an
      investigator would need to increase the Z used as a test criterion, by
      approximately 0.30 LOD units for analyses as in (1) or (2) and by 0.60 Z units
      for analyses as in (3). These guidelines, which are valid up to approximately Z =
      3.0, are conservative for (1) and are very conservative for (2) and (3). By
      quantifying the increase in significance level (or, correspondingly, the increase
      in Z), our findings will enable users to rationally assess the advantages versus
      the disadvantages of mod scores.

PMID- 8981966
TI  - The (Ala-Val) mutation of methylenetetrahydrofolate reductase as a genetic risk
      factor for vascular disease in non-insulin-dependent diabetic patients.

PMID- 8981967
TI  - Differences in methylenetetrahydrofolate reductase genotype frequencies, between
      Whites and Blacks.

PMID- 8981968
TI  - Prevalence and parental origin of de novo 1.5-Mb duplication in Charcot-Marie
      Tooth disease type 1A.

PMID- 8981969
TI  - Prevalence and parental origin of de novo RET mutations in multiple endocrine
      neoplasia type 2A and familial medullary thyroid carcinoma. Le Groupe d'Etude des
      Tumeurs a Calcitonine.

PMID- 8981970
TI  - Expression of DAZ, an azoospermia factor candidate, in human spermatogonia.

PMID- 8981971
TI  - mtDNA and Y chromosome-specific polymorphisms in modern Ojibwa: implications
      about the origin of their gene pool.

PMID- 8981972
TI  - Diagnostic testing: a cost analysis for Prader-Willi and Angelman syndromes.

PMID- 8981973
TI  - Transcriptional regulation and locations of Agrobacterium tumefaciens genes
      required for complete catabolism of octopine.
AB  - By screening for octopine-inducible gene expression, we previously identified all
      the genes required for utilization of octopine as a source of carbon, nitrogen,
      and energy. They are (i) octopine oxidase, which converts octopine to arginine
      and pyruvate and is encoded by the ooxAB operon, (ii) arginase, which converts
      arginine to ornithine and urea and is encoded by arcA, (iii) ornithine
      cyclodeaminase, which converts ornithine to proline and ammonia and is encoded by
      the homologous arcB and ocd genes, and (iv) proline dehydrogenase, which converts
      proline to glutamate and is encoded by putA. Here we describe the regulation and
      localization of each of these genes. The ooxA-ooxB-ocd operon was previously
      shown to reside on the Ti plasmid and to be directly inducible by octopine. The
      arcAB operon is directly inducible by arginine, while it is induced by octopine
      only in strains that can convert octopine to arginine. Ornithine may also be a
      direct inducer of arcAB. putA is directly inducible by proline, while induction
      by octopine and by arginine (and probably by ornithine) requires their conversion
      to proline. Genetic studies indicate that arcAB and putA are localized on a
      conjugal genetic element. This element can be transferred to other Agrobacterium
      tumefaciens strains by a mechanism that does not require recA-dependent
      homologous recombination. Transfer of this genetic element from A. tumefaciens
      R10 requires at least one tra gene found on its Ti plasmid, indicating that this
      element is not self-transmissible but is mobilizable by the Ti plasmid. The DNA
      containing the arcAB and putA genes comigrates with a 243-kb linear molecular
      weight standard on field inversion electrophoretic gels.

PMID- 8981974
TI  - Cell wall monoglycine cross-bridges and methicillin hypersusceptibility in a
      femAB null mutant of methicillin-resistant Staphylococcus aureus.
AB  - The femAB operon is involved in the formation of the characteristic pentaglycine
      side chain of the staphylococcal peptidoglycan. Allele replacement of the femAB
      operon with the tetracycline resistance determinant tetK in a methicillin
      resistant Staphylococcus aureus strain resulted in impaired growth, methicillin
      hypersusceptibility, and lysostaphin resistance. The usual pentaglycine cross
      bridges were replaced by monoglycine bridges exclusively, and cross-linking of
      the peptidoglycan strands was drastically reduced. Complementation of the femAB
      null mutant by either femA or femAB resulted in the extension of the cross
      bridges to a triglycine or a pentaglycine, respectively. This finding suggests
      that FemA is responsible for the formation of glycines 2 and 3, and FemB is
      responsible for formation of glycines 4 and 5, of the pentaglycine side chain of
      the peptidoglycan precursor. Moreover, it can be deduced that addition of the
      first glycine must occur by a femAB-independent mechanism.

PMID- 8981976
TI  - Photoresponses in Rhodobacter sphaeroides: role of photosynthetic electron
      transport.
AB  - Rhodobacter sphaeroides responds to a decrease in light intensity by a transient
      stop followed by adaptation. There is no measurable response to increases in
      light intensity. We confirmed that photosynthetic electron transport is essential
      for a photoresponse, as (i) inhibitors of photosynthetic electron transport
      inhibit photoresponses, (ii) electron transport to oxidases in the presence of
      oxygen reduces the photoresponse, and (iii) the magnitude of the response is
      dependent on the photopigment content of the cells. The photoresponses of cells
      grown in high light, which have lower concentrations of light-harvesting
      photopigment and reaction centers, saturated at much higher light intensities
      than the photoresponses of cells grown in low light, which have high
      concentrations of light-harvesting pigments and reaction centers. We examined
      whether the primary sensory signal from the photosynthetic electron transport
      chain was a change in the electrochemical proton gradient or a change in the rate
      of electron transport itself (probably reflecting redox sensing). R. sphaeroides
      showed no response to the addition of the proton ionophore carbonyl cyanide 4
      trifluoromethoxyphenylhydrazone, which decreased the electrochemical proton
      gradient, although a behavioral response was seen to a reduction in light
      intensity that caused an equivalent reduction in proton gradient. These results
      strongly suggest that (i) the photosynthetic apparatus is the primary
      photoreceptor, (ii) the primary signal is generated by a change in the rate of
      electron transport, (iii) the change in the electrochemical proton gradient is
      not the primary photosensory signal, and (iv) stimuli affecting electron
      transport rates integrate via the electron transport chain.

PMID- 8981977
TI  - Metal selectivity of in situ microcolonies in biofilms of the Elbe river.
AB  - The ultrastructure of natural complex biofilm communities of the Elbe river grown
      in situ on microscopic glass coverslips was studied by using transmission
      electron microscopy and energy-dispersive x-ray (EDX) analysis. Characteristic
      microcolonies which measured between 3.3 and 9.3 microm in diameter were
      frequently observed. They had an outer envelope and harbored 6 to 30 cells. The
      cells formed short rods measuring 1.09 +/- 0.28 microm (n = 10) in length and
      0.55 + 0.07 microm (n = 21) in width. They were surrounded by a thick layer of
      electron-transparent, nonosmicated matter, 120 to 300 nm thick. Individual cells
      exhibited a unique ultrastructural trait, namely, a concentric membrane stack
      which completely surrounded the cytoplasm. It consisted of three membrane
      doublets, which showed an overall thickness of 57 to 66 nm. The center-to-center
      spacing between two membrane doublets was 22.2 +/- 1.0 nm (n = 12). The bacterial
      cell wall seemed to be of the gram-negative type. The fact that upon shrinkage
      hexagonal clefts appeared proved the cells to be tightly packed, and septum
      formation by binary fissions was observed. All of these morphological details
      indicate that the cells within these microcolonies were actively growing and did
      not represent spore-like states. EDX analysis showed that only the electron-dense
      surface deposit of the microcolonies contained Mn and Fe in significant amounts,
      while these two elements were absent from the intercellular space and the
      cytoplasm of the microorganisms. In contrast, aluminum ions were able to
      penetrate the outer envelope of the microcolonies and were detected in the
      intercellular space. They were, however, completely absent from the microbial
      cytoplasm, indicating a filter cascade with respect to aluminum. From the
      ultrastructural data together with the deposition of iron and manganese on the
      microcolony surface, it appears that these organisms may belong to the genus
      Siderocapsa or Nitrosomonas. They do not precisely match any of the described
      species and may therefore represent a new species.

PMID- 8981975
TI  - The alternative sigma factor sigma28 of Legionella pneumophila restores
      flagellation and motility to an Escherichia coli fliA mutant.
AB  - Gene expression in Legionella pneumophila, the etiological agent of Legionnaires'
      disease, can be controlled by alternative forms of RNA polymerase programmed by
      distinct sigma factors. To understand the regulation of L. pneumophila flagellin
      expression, we cloned the sigma factor (FliA) of RNA polymerase responsible for
      the transcription of the flagellin gene, flaA. FliA is a member of the sigma28
      class of alternative sigma factors identified in several bacterial genera. The
      gene fliA has been isolated from an expression library of L. pneumophila isolate
      Corby in Escherichia coli K-12. This library was transformed into a fliA mutant
      of E. coli K-12 containing a plasmid carrying the L. pneumophila-specific flaA
      promoter fused to the reporter gene luxAB. Screening the obtained transformants
      for luciferase activity, we isolated the major part of the fliA gene on a 1.64-kb
      fragment. This fragment was sequenced and used for reverse PCR in order to
      recover the complete fliA gene. The resulting 1.03-kb fragment was shown to
      contain the entire fliA gene. L. pneumophila FliA has 55 and 43% amino acid
      identity with the homologous sequences of Pseudomonas aeruginosa and E. coli.
      Furthermore, the L. pneumophila fliA gene was able to restore the flagellation
      and the motility defect of an E. coli fliA mutant. This result suggests that the
      L. pneumophila sigma28 protein can bind to the E. coli core RNA polymerase to
      direct transcription initiation from the flaA-specific promoter.

PMID- 8981978
TI  - Characterization of fhlA mutations resulting in ligand-independent
      transcriptional activation and ATP hydrolysis.
AB  - The FhlA protein belongs to the NtrC family of transcriptional regulators. It
      induces transcription from the -12/-24 promoters of the genes of the formate
      regulon by sigma54 RNA polymerase. FhlA is activated by binding of the ligand
      formate and does not require phosphorylation. A mutational analysis of the fhLA
      gene portion coding for the A and C domains was conducted with the aim of gaining
      information on the interaction between formate binding and ATP hydrolysis plus
      transcription activation. Four mutations were identified, all located in the A
      domain; one of them rendered transcription completely independent from the
      presence of formate, and the others conferred a semiconstitutive phenotype. The
      FhlA protein of one of the semiconstitutive variants was purified. Catalytic
      efficiency of ATP hydrolysis of the mutant FhlA was increased in the absence of
      formate in the same manner as formate influences the activity of wild-type FhlA.
      Moreover, in vitro transcription occurred at much lower threshold concentrations
      of the mutant protein and of nucleoside triphosphates than with the wild-type
      FhlA.

PMID- 8981979
TI  - The processive endocellulase CelF, a major component of the Clostridium
      cellulolyticum cellulosome: purification and characterization of the recombinant
      form.
AB  - The recombinant form of the cellulase CelF of Clostridium cellulolyticum, tagged
      by a C-terminal histine tail, was overproduced in Escherichia coli. The fusion
      protein was purified by affinity chromatography on a Ni-nitrilotriacetic acid
      column. The intact form of CelF (Mr, 79,000) was rapidly degraded at the C
      terminus, giving a shorter stable form, called truncated CelF (Mr, 71,000). Both
      the entire and the truncated purified forms degraded amorphous cellulose (kcat =
      42 and 30 min(-1), respectively) and microcrystalline cellulose (kcat = 13 and 10
      min(-1), respectively). The high ratio of soluble reducing ends to insoluble
      reducing ends released by truncated CelF from amorphous cellulose showed that
      CelF is a processive enzyme. Nevertheless, the diversity of the cellodextrins
      released by truncated CelF from phosphoric acid-swollen cellulose at the
      beginning of the reaction indicated that the enzyme might randomly hydrolyze beta
      1,4 bonds. This hypothesis was supported by viscosimetric measurements and by the
      finding that CelF and the endoglucanase CelA are able to degrade some of the same
      cellulose sites. CelF was therefore called a processive endocellulase. The
      results of immunoblotting analysis showed that CelF was associated with the
      cellulosome of C. cellulolyticum. It was identified as one of the three major
      components of cellulosomes. The ability of the entire form of CelF to interact
      with CipC, the cellulosome integrating protein, or mini-CipC1, a recombinant
      truncated form of CipC, was monitored by interaction Western blotting
      (immunoblotting) and by binding assays using a BIAcore biosensor-based analytical
      system.

PMID- 8981981
TI  - Characterization of a region of the IncHI2 plasmid R478 which protects
      Escherichia coli from toxic effects specified by components of the tellurite,
      phage, and colicin resistance cluster.
AB  - The IncHI2 plasmid R478 specifies resistance to potassium tellurite (Te(r)), to
      some bacteriophages (Phi), and to pore-forming colicins (PacB). The genes
      encoding the three phenotypes are linked, and an 8.4-kb fragment of R478 DNA
      encoding them cannot be subcloned unless cocloned with a second section of the
      plasmid. Subclone pKFW4A contains a 5.9-kb BamHI-EcoRI fragment which caused some
      toxicity when present in Escherichia coli cells. Bacterial cells containing
      freshly transformed pKFW4A, examined by light microscopy and electron microscopy,
      had a filamentous morphology consistent with a block in septation. Insertion of
      transposon Tn1000 into terZ, -A, -B, and -C genes of pKFW4A resulted in the loss
      of the filamentation phenotype. Deletion of several regions of the clone
      confirmed that these latter components are involved in the filamentation
      phenotype. The region specifying protection from toxicity caused by the larger
      8.4-kb fragment (encompassing this cluster and the entire 5.9-kb section of
      pKFW4A) was sequenced and analyzed by T7 polymerase expression and Tn1000
      mutagenesis. Three open reading frames, terW, terY, and terX, were identified in
      a 2.6-kb region. Two polypeptides with approximate molecular masses of 18 and 28
      kDa were expressed in CSRDE3 cells and were consistent with TerW (17.1 kDa; 155
      amino acids [aa]) and TerY (26.9 kDa; 248 aa), whereas a protein of 213 aa
      deduced from terX was not observed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The terX gene product shows strong identity with the previously
      identified TerE, TerD, and TerZ polypeptides, and there is a conserved motif of
      13 residues, GDN(R/L)TG(E/A)GDGDDE, within this group of polypeptides.
      Complementation analysis indicated that terW, located approximately 6.0 kb
      upstream of terZ, brings about protection of cells from toxic effects of
      components of the Te(r), Phi, and PacB cluster.

PMID- 8981980
TI  - Characterization of three distinct extradiol dioxygenases involved in
      mineralization of dibenzofuran by Terrabacter sp. strain DPO360.
AB  - The dibenzofuran-degrading bacterial strain DPO360 represents a new species of
      the genus Terrabacter together with the previously described dibenzofuran
      mineralizing bacterial strain DPO1361 (K.-H. Engesser, V. Strubel, K.
      Christoglou, P. Fischer, and H. G. Rast, FEMS Microbiol. Lett. 65:205-210, 1989;
      V. Strubel, Ph.D. thesis, University of Stuttgart, Stuttgart, Germany, 1991; V.
      Strubel, H. G. Rast, W. Fietz, H.-J. Knackmuss, and K.-H. Engesser, FEMS
      Microbiol. Lett. 58:233-238, 1989). Two 2,3-dihydroxybiphenyl-1,2-dioxygenases
      (BphC1 and BphC2) and one catechol-2,3-dioxygenase (C23O) were shown to be
      expressed in Terrabacter sp. strain DPO360 growing with dibenzofuran as a sole
      source of carbon and energy. These enzymes exhibited strong sensitivity to
      oxygen. They were purified to apparent homogeneity as homodimers (BphC and BphC2)
      and as a homotetrameric catechol-2,3-dioxygenase (C23O). According to their
      specificity constants kcat/Km, both BphC1 and BphC2 were shown to be responsible
      for the cleavage of 2,2',3-trihydroxybiphenyl, the first metabolite in
      dibenzofuran mineralization along the angular dioxygenation pathway. With this
      substrate, BphC2 exhibited a considerably higher kcat/Km, value (183 microM/min)
      than BphC1 (29 microM/min). Catechol-2,3-dioxygenase was recognized to be not
      involved in the ring cleavage of 2,2',3-trihydroxybiphenyl (kcat/Km, 1
      microM/min). Analysis of deduced amino acid sequence data of bphC1 revealed 36%
      sequence identity to nahC from Pseudomonas putida PpG7 (S. Harayama and M. Rekik,
      J. Biol. Chem. 264:15328-15333, 1989) and about 40% sequence identity to various
      bphC genes from different Pseudomonas and Rhodococcus strains. In addition,
      another 2,3-dihydroxybiphenyl-1,2-dioxygenase gene (bphC3) was cloned from the
      genome of Terrabacter sp. strain DPO360. Expression of this gene, however, could
      not be detected in Terrabacter sp. strain DPO360 after growth with dibenzofuran.

PMID- 8981982
TI  - Purification of an extracellular D-(-)-3-hydroxybutyrate oligomer hydrolase from
      Pseudomonas sp. strain A1 and cloning and sequencing of its gene.
AB  - An extracellular D-(-)-3-hydroxybutyrate oligomer hydrolase was purified from a
      poly(3-hydroxybutyrate)-degrading bacterium, Pseudomonas sp. strain A1. The
      purified enzyme hydrolyzed the D-(-)-3-hydroxybutyrate dimer and trimer at
      similar rates. The enzyme activity was inhibited by a low concentration of
      diisopropylfluorophosphate. The molecular weight of the hydrolase was estimated
      to be about 70,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      A 10-kbp DNA fragment of A1 was detected by hybridization with the gene (2 kbp)
      of an extracellular poly(3-hydroxybutyrate) depolymerase from Alcaligenes
      faecalis. Subsequent subcloning showed that a SmaI-KpnI fragment (2.8 kbp) was
      responsible for expression of the hydrolase in Escherichia coli and an in vitro
      transcription-translation system. The expressed protein detected by
      immunostaining had the same molecular weight as the purified enzyme from A1. The
      protein band detected in the in vitro transcription-translation system had a
      molecular size of 72 kDa. The nucleotide sequence of the SmaI-KpnI fragment was
      determined, and one open reading frame (2,112 nucleotides) was found. It
      specifies a protein with a deduced molecular weight of 72,876 (704 amino acids).
      In this sequence, the consensus sequence of serine-dependent hydrolysis, G-X-S-X
      G, did not exist.

PMID- 8981983
TI  - Interactions between VirB9 and VirB10 membrane proteins involved in movement of
      DNA from Agrobacterium tumefaciens into plant cells.
AB  - The 11 VirB proteins from Agrobacterium tumefaciens are predicted to form a
      membrane-bound complex that mediates the movement of DNA from the bacterium into
      plant cells. The studies reported here on the possible VirB protein interactions
      in such a complex demonstrate that VirB9 and VirB10 can each form high-molecular
      weight complexes after treatment with a chemical cross-linker. Analysis of
      nonpolar virB mutants showed that the formation of the VirB10 complexes does not
      occur in a virB9 mutant and that VirB9 and VirB10 are not components of the same
      cross-linked complex. VirB9, when stabilized by the concurrent expression of
      VirB7, was shown to be sufficient to permit VirB10 to cross-link into its usual
      high-molecular-weight forms in the absence of other Vir proteins. Randomly
      introduced single point mutations in virB9 resulted in Agrobacterium strains with
      severely attenuated virulence. Although some of the mutants contained wild-type
      levels of VirB9 and displayed an unaltered VirB9 cross-linking pattern, VirB10
      cross-linking was drastically reduced. We conclude that specific amino acid
      residues in VirB9 are necessary for interaction with VirB10 resulting in the
      capacity of VirB10 to participate in high-molecular-weight complexes that can be
      visualized by chemical cross-linking.

PMID- 8981984
TI  - Trichloroethylene oxidation by purified toluene 2-monooxygenase: products,
      kinetics, and turnover-dependent inactivation.
AB  - Trichloroethylene is oxidized by several types of nonspecific bacterial
      oxygenases. Toluene 2-monooxygenase from Burkholderia cepacia G4 is implicated in
      trichloroethylene oxidation and is uniquely suggested to be resistant to turnover
      dependent inactivation in vivo. In this work, the oxidation of trichloroethylene
      was studied with purified toluene 2-monooxygenase. All three purified toluene 2
      monooxygenase protein components and NADH were required to reconstitute full
      trichloroethylene oxidation activity in vitro. The apparent Km and Vmax were 12
      microM and 37 nmol per min per mg of hydroxylase component, respectively. Ten
      percent of the full activity was obtained when the small-molecular-weight enzyme
      component was omitted. The stable oxidation products, accounting for 84% of the
      trichloroethylene oxidized, were carbon monoxide, formic acid, glyoxylic acid,
      and covalently modified oxygenase proteins that constituted 12% of the reacted
      [14C]trichloroethylene. The stable oxidation products may all derive from the
      unstable intermediate trichloroethylene epoxide that was trapped by reaction with
      4-(p-nitrobenzyl)pyridine. Chloral hydrate and dichloroacetic acid were not
      detected. This finding differs from that with soluble methane monooxygenase and
      cytochrome P-450 monooxygenase, which produce chloral hydrate. Trichloroethylene
      dependent inactivation of toluene 2-monooxygenase activity was observed. All of
      the protein components were covalently modified during the oxidation of
      trichloroethylene. The addition of cysteine to reaction mixtures partially
      protected the enzyme system against inactivation, most notably protecting the
      NADH-oxidoreductase component. This suggested the participation of diffusible
      intermediates in the inactivation of the oxidoreductase.

PMID- 8981985
TI  - The VanS sensor negatively controls VanR-mediated transcriptional activation of
      glycopeptide resistance genes of Tn1546 and related elements in the absence of
      induction.
AB  - Transposon Tn1546 from Enterococcus faecium BM4147 encodes a histidine protein
      kinase (VanS) and a response regulator (VanR) that regulate transcription of the
      vanHAX operon encoding a dehydrogenase (VanH), a ligase (VanA), and a D,D
      dipeptidase (VanX). These last three enzymes confer resistance to glycopeptide
      antibiotics by production of peptidoglycan precursors ending in the depsipeptide
      D-alanyl-D-lactate. Transcription of vanS and the role of VanS in the regulation
      of the vanHAX operon were analyzed by inserting a cat reporter gene into vanS.
      Transcription of cat and vanX was inducible by glycopeptides in partial diploids
      harboring vanS and vanS(omega)cat but was constitutive in strains containing only
      vanS(omega)cat. Promoters P(R) and P(H), located upstream from vanR and vanH,
      respectively, were cloned into a promoter probing vector to study transactivation
      by chromosomally encoded VanR and VanS. The promoters were inactive in the
      absence of vanR and vanS, inducible by glycopeptides in the presence of both
      genes, and constitutively activated by VanR in the absence of VanS. Thus,
      induction of the vanHAX operon involves an amplification loop resulting from
      binding of phospho-VanR to the P(R) promoter and increased transcription of the
      vanR and vanS genes. Full activation of P(R) and P(H) by VanR was observed in the
      absence of VanS, indicating that the sensor negatively controls VanR in the
      absence of glycopeptides, presumably by dephosphorylation. Activation of the VanR
      response regulator in the absence of VanS may involve autophosphorylation of VanR
      with acetyl phosphate or phosphorylation by a heterologous histidine protein
      kinase.

PMID- 8981987
TI  - 2-Naphthoate catabolic pathway in Burkholderia strain JT 1500.
AB  - Burkholderia strain (JT 1500), able to use 2-naphthoate as the sole source of
      carbon, was isolated from soil. On the basis of growth characteristics, oxygen
      uptake experiments, enzyme assays, and detection of intermediates, a degradation
      pathway of 2-naphthoate is proposed. The features of this pathway are convergent
      with those for phenanthrene. We propose a pathway for the conversion of 2
      naphthoate to 1 mol (each) of pyruvate, succinate, and acetyl coenzyme A and 2
      mol of CO2. During growth in the presence of 2-naphthoate, six metabolites were
      detected by thin-layer chromatography, high-performance liquid chromatography,
      and spectroscopy. 1-Hydroxy-2-naphthoate accumulated in the culture broth during
      growth on 2-naphthoate. Also, the formation of 2'-carboxybenzalpyruvate,
      phthalaldehydate, phthalate, protocatechuate, and beta-carboxy-cis,cis-muconic
      acid was demonstrated. (1R,2S)-cis-1,2-Dihydro-1,2-dihydroxy-2-naphthoate was
      thus considered an intermediate between 2-naphthoate and 1-hydroxy-2-naphthoate,
      but it was not transformed by whole cells or their extracts. We conclude that
      this diol is not responsible for the formation of 1-hydroxy-2-naphthoate from 2
      naphthoate but that one of the other three diastereomers is not eliminated as a
      potential intermediate for a dehydration reaction.

PMID- 8981986
TI  - The lonS gene regulates swarmer cell differentiation of Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus differentiates from a polarly flagellated, short, rod
      shaped cell known as the swimmer to the elongated, hyperflagellated, and
      multinucleated swarmer cell type when it is grown on a surface. The swarmer is
      adapted to movement over and colonization of surfaces. To understand the signal
      transduction mechanism by which the bacterium recognizes surfaces and reprograms
      gene expression, we isolated a new class of mutants defective in surface sensing.
      These mutants were constitutive for swarmer cell gene expression, inappropriately
      expressing high levels of a swarmer cell gene fusion product when grown in
      liquid. They showed no defect in the swimming motility system, unlike all
      previously isolated constitutive mutants which have defects in the alternate,
      polar motility system. The lesions in the majority of the newly isolated mutants
      were found to be in a gene, lonS, which encodes a polypeptide exhibiting 81%
      sequence identity to the Escherichia coli Lon protein, an ATP-dependent protease.
      Upstream sequences preceding the lonS coding region resemble a heat shock
      promoter, and the homology extends to sequences flanking lonS. The gene order
      appears to be clpX lonS hupB, like the organization of the E. coli locus. V.
      parahaemolyticus lonS complemented E. coli lon mutants to restore UV resistance
      and capsular polysaccharide regulation to that of the wild type. Vibrio lonS
      mutants were UV sensitive. In addition, when grown in liquid and examined in a
      light microscope, lonS mutant cells were extremely long and thus resembled
      swarmer cells harvested from a surface.

PMID- 8981988
TI  - Denaturation of circular or linear DNA facilitates targeted integrative
      transformation of Streptomyces coelicolor A3(2): possible relevance to other
      organisms.
AB  - Using Streptomyces coelicolor A3(2) protoplasts, the number of transformants
      obtained by homologous recombination of incoming double-stranded circular DNA
      with the recipient chromosome was greatly stimulated by simple denaturation of
      the donor DNA. This procedure was very effective with inserts over a ca. 100-fold
      size range, the largest tested being ca. 40-kb inserts in cosmids. These
      observations led to transformation experiments with linearized cloned DNA and
      randomly sheared genomic DNA. In both cases, DNA denaturation led to significant
      levels of transformation. Most of the transformants had resulted from the
      predicted homologous recombination events. A number of genetic manipulations will
      be made easier or possible by these procedures.

PMID- 8981989
TI  - Molecular genetic analysis suggesting interactions between AppA and PpsR in
      regulation of photosynthesis gene expression in Rhodobacter sphaeroides 2.4.1.
AB  - The AppA protein plays an essential regulatory role in development of the
      photosynthetic apparatus in the anoxygenic phototrophic bacterium Rhodobacter
      sphaeroides 2.4.1 (M. Gomelsky and S. Kaplan, J. Bacteriol. 177:4609-4618, 1995).
      To gain additional insight into both the role and site of action of AppA in the
      regulatory network governing photosynthesis gene expression, we investigated the
      relationships between AppA and other known regulators of photosynthesis gene
      expression. We determined that AppA is dispensable for development of the
      photosynthetic apparatus in a ppsR null background, where PpsR is an aerobic
      repressor of genes involved in photopigment biosynthesis and puc operon
      expression. Moreover, all suppressors of an appA null mutation thus far isolated,
      showing improved photosynthetic growth, were found to contain mutations in the
      ppsR gene. Because ppsR gene expression in R. sphaeroides 2.4.1 appears to be
      largely independent of growth conditions, we suggest that regulation of repressor
      activity occurs predominately at the protein level. We have also found that PpsR
      functions as a repressor not only under aerobic but under anaerobic
      photosynthetic conditions and thereby is involved in regulating the abundance of
      the light harvesting complex II, depending on light intensity. It seems likely
      therefore, that PpsR responds to an integral signal (e.g., changes in redox
      potential) produced either by changes in oxygen tension or light intensity. The
      profile of the isolated suppressor mutations in PpsR is in accord with this
      proposition. We propose that AppA may be involved in a redox-dependent modulation
      of PpsR repressor activity.

PMID- 8981990
TI  - Role of transmembrane pH gradient and membrane binding in nisin pore formation.
AB  - Nisin is a cationic antimicrobial peptide that belongs to the group of
      lantibiotics. It is thought to form oligomeric pores in the target membrane by a
      mechanism that requires the transmembrane electrical potential delta psi and that
      involves local pertubation of the lipid bilayer structure. Here we show that
      nisin does not form exclusively voltage-dependent pores: even in the absence of a
      delta psi, nisin is able to dissipate the transmembrane pH gradient (delta pH) in
      sensitive Lactococcus lactis cells and proteoliposomes. The rate of dissipation
      increases with the magnitude of the delta pH. Nisin forms pores only when the
      delta pH is inside alkaline. The efficiency of delta psi-induced pore formation
      is strongly affected by the external pH, whereas delta pH-induced pore formation
      is rather insensitive to the external pH. Nisin(1-12), an amino-terminal fragment
      of nisin, and (des-deltaAla5)-(nisin(1-32) amide have a strongly reduced capacity
      to dissipate the delta psi and delta pH in cytochrome c oxidase proteoliposomes
      and L. lactis cells. Both variants bind with reduced efficiency to liposomes
      containing negatively charged phospholipids, suggesting that both ring A and
      rings C to E play a role in membrane binding. Nisin(1-12) competes with nisin for
      membrane binding and antagonizes pore formation. These findings are consistent
      with the wedge model of nisin-induced pore formation.

PMID- 8981991
TI  - In vitro inhibitory activity of RepC/C*, the inactivated form of the pT181
      plasmid initiation protein, RepC.
AB  - pT181 is a Staphylococcus aureus rolling circle plasmid that regulates its
      replication by controlling the synthesis of its dimeric initiator protein RepC/C
      and by inactivating the protein following its use in replication (A. Rasooly and
      R. P. Novick, Science 262:1048-1050, 1993). This inactivation consists of the
      addition of an oligonucleotide, representing several nucleotides immediately 3'
      to the initiation nick site, to the active site tyrosine of one of the two
      subunits, generating a heterodimer, RepC/C*. Previous results suggested that the
      inactive form was metabolically stable and was present at a much higher level
      than the active form (A. Rasooly and R. P. Novick, Science 262:1048-1050, 1993).
      In the present study we have measured total RepC antigen as a function of plasmid
      copy number and have analyzed the interaction of the two forms. We find that
      pT181-containing staphylococci contain approximately one RepC dimer per plasmid
      copy over a 50-fold range of copy numbers. This is consistent with previous
      measurements of the rate of RepC synthesis, which suggested that one RepC dimer
      is synthesized per replication event (J. Bargonetti, P.-Z. Wang and R. P. Novick,
      EMBO J. 12:3659-3667, 1993). The RepC/C* heterodimer, which is inactive for
      replication, is a competitive inhibitor of the replication and the topoisomerase
      like and cruciform-enhancing activities of the native protein. These results
      suggest that the inactive form may have a specific regulatory role in vivo. Since
      the known plasmid-determined controls, which maintain a constant plasmid copy
      number, are designed to ensure the synthesis of one RepC/C dimer per plasmid
      replication event, it is difficult to envision any role for yet another negative
      regulator of replication. Conceivably, under conditions where the initiator is
      overproduced, such as in the absence of the normal antisense regulation of
      initiator production, RepC/C* could serve as a fail-safe means of preventing
      autocatalytic replication.

PMID- 8981992
TI  - Fine-structure evidence for cell membrane partitioning of the nucleoid and
      cytoplasm during bud formation in Hyphomonas species.
AB  - Hyphomonas spp. reproduce by budding from the tip of the prosthecum, distal to
      the main body of the reproductive cell; thus, the chromosome must travel through
      the prosthecum to enter the progeny, the swarm cell. When viewed by electron
      microscopy, negatively stained whole cells, ultrathin-sectioned cells, and freeze
      etched and frozen hydrated cells all had marked swellings of the cytoplasmic
      membrane (CM) in the prosthecum which are termed pseudovesicles (PV). PV were
      separated by constrictions in the contiguous CM. In replicating cells, PV housed
      ribosomes and DNA, which was identified by its fibrillar appearance and by
      lactoferrin-gold labeling. The micrographs also revealed that the CM bifurcates
      at the origin of the prosthecum so that one branch partitions the main body of
      the reproductive cell from the prosthecum and swarm cell. The results of this
      fine-structure analysis suggest models explaining DNA segregation and the marked
      asymmetric polarity of the budding reproductive cell.

PMID- 8981993
TI  - Expression of bacterial mtlD in Saccharomyces cerevisiae results in mannitol
      synthesis and protects a glycerol-defective mutant from high-salt and oxidative
      stress.
AB  - Polyols, or polyhydroxy alcohols, are produced by many fungi. Saccharomyces
      cerevisiae produces large amounts of glycerol, and several fungi that cause
      serious human infections produce D-arabinitol and mannitol. Glycerol functions as
      an intracellular osmolyte in S. cerevisiae, but the functions of D-arabinitol and
      mannitol in pathogenic fungi are not yet known. To investigate the functions of
      mannitol, we constructed a new mannitol biosynthetic pathway in S. cerevisiae. S.
      cerevisiae transformed with multicopy plasmids encoding the mannitol-1-phosphate
      dehydrogenase of Escherichia coli produced mannitol, whereas S. cerevisiae
      transformed with control plasmids did not. Although mannitol production had no
      obvious phenotypic effects in wild-type S. cerevisiae, it restored the ability of
      a glycerol-defective, osmosensitive osg1-1 mutant to grow in the presence of high
      NaCl concentrations. Moreover, osg1-1 mutants producing mannitol were more
      resistant to killing by oxidants produced by a cell-free H2O2-FeSO4-NaI system
      than were controls. These results indicate that mannitol can (i) function as an
      intracellular osmolyte in S. cerevisiae, (ii) substitute for glycerol as the
      principal intracellular osmolyte in S. cerevisiae, and (iii) protect S.
      cerevisiae from oxidative damage by scavenging toxic oxygen intermediates.

PMID- 8981994
TI  - Gene transcription and chromosome replication in Escherichia coli.
AB  - Transcript levels of several Escherichia coli genes involved in chromosome
      replication and cell division were measured in dnaC2(Ts) mutants synchronized for
      chromosome replication by temperature shifts. Levels of transcripts from four of
      the genes, dam, nrdA, mukB, and seqA, were reduced at a certain stage during
      chromosome replication. The magnitudes of the decreases were similar to those
      reported previously ftsQ and ftsZ (P. Zhou and C. E. Helmstetter, J. Bacteriol.
      176:6100-6106, 1994) but considerably less than those seen with dnaA, gidA, and
      mioC (P. W. Theisen, J. E. Grimwade, A. C. Leonard, J. A. Bogan, and C. E.
      Helmstetter, Mol. Microbiol. 10:575-584, 1993). The decreases in transcripts
      appeared to correlate with the estimated time at which the genes replicated. This
      same conclusion was reached in studies with synchronous cultures obtained with
      the baby machine in those instances in which periodicities in transcript levels
      were clearly evident. The transcriptional levels for two genes, minE and tus, did
      not fluctuate significantly, whereas the transcripts for one gene, iciA, appeared
      to increase transiently. The results support the idea that cell cycle timing in
      E. coli is not governed by timed bursts of gene expression, since the overall
      findings summarized in this report are generally consistent with cell cycle
      dependent transient inhibitions of transcription rather than stimulations.

PMID- 8981995
TI  - Molecular cloning and characterization of the obg gene of Streptomyces griseus in
      relation to the onset of morphological differentiation.
AB  - Morphological differentiation in microorganisms is usually accompanied by a
      decrease in intracellular GTP pool size, as has been demonstrated in bacillaceae,
      streptomycetaceae, and yeasts. The obg gene, which codes for a GTP-binding
      protein belonging to the GTPase superfamily of proteins, was cloned from
      Streptomyces griseus IFO13189. The gene is located just downstream of the genes
      for ribosomal proteins L21 and L27, encoded a protein of 478 amino acids (51
      kDa), and possessed three consensus motifs which confer GTP-binding ability; Obg
      protein expressed in Escherichia coli bound GTP, as demonstrated using a UV cross
      linking method. Introduction of multiple copies of obg into wild-type S. griseus
      suppressed aerial mycelium development in cells on solid media. However, no
      effect on streptomycin production was detected, indicating that Obg is involved
      in the regulation of the onset of morphological but not physiological
      differentiation. Multiple copies of obg also suppressed submerged spore formation
      in liquid culture. Southern hybridization studies indicated that genes homologous
      to obg exist widely in streptomycetes, and an obg homolog was successfully cloned
      from S. coelicolor A3(2). We propose that by monitoring the intracellular GTP
      pool size, the Obg protein is involved in sensing changes in the nutritional
      environment leading ultimately to morphological differentiation.

PMID- 8981996
TI  - Use of rpsL for dominance selection and gene replacement in Streptomyces
      roseosporus.
AB  - We developed a gene replacement system using the rpsL gene of Streptomyces
      roseosporus and demonstrated its utility by constructing a deletion in the S.
      roseosporus glnA gene. A 1.3-kb BamHI fragment that hybridized to the
      Mycobacterium smegmatis rpsL gene was subcloned from an S. roseosporus cosmid
      library and sequenced. Plasmid pRHB514 containing the rpsL gene conferred
      streptomycin sensitivity (Sm(S)) to the Sm(r) S. roseosporus TH149. The
      temperature-sensitive plasmid pRHB543 containing rpsL and the S. roseosporus glnA
      gene disrupted with a hygromycin resistance (Hm(r)) gene was introduced into S.
      roseosporus TH149, and recombinants containing single and double crossovers were
      obtained after a temperature increase. Southern hybridization analysis revealed
      that single crossovers occurred in the glnA or rpsL genes and that double
      crossovers resulted in replacement of the chromosomal glnA gene with the
      disrupted glnA. Glutamine synthetase activity was undetectable in the recombinant
      containing the disrupted glnA gene.

PMID- 8981997
TI  - Identification of the algZ gene upstream of the response regulator algR and its
      participation in control of alginate production in Pseudomonas aeruginosa.
AB  - Alginate production in mucoid Pseudomonas aeruginosa isolates from cystic
      fibrosis patients is under direct control by AlgU, the P. aeruginosa equivalent
      of the extreme heat shock sigma factor sigma(E) in gram-negative bacteria, and
      AlgR, a response regulator from the superfamily of two-component signal
      transduction systems. In this report, we describe the identification of the algZ
      gene, located immediately upstream of algR, which is involved in the control of
      alginate production. The predicted product of the algZ gene showed similarity to
      a subset of sensory components from the superfamily of signal transduction
      systems but lacked several of the highly conserved motifs typical of histidine
      protein kinases. Inactivation of algZ in the wild-type standard genetic strain
      PAO1 did not affect its nonmucoid morphology. However, inactivation of algZ in a
      mucoid mutant P. aeruginosa strain, which had AlgU freed from control by the anti
      sigma factor MucA, resulted in increased alginate production under growth
      conditions which did not permit expression of mucoidy in the parental algZ+
      strain. The observed effects were abrogated when algR was inactivated in the
      algZ::Tc(r) background. These findings indicate that algZ plays a regulatory role
      in alginate production, possibly interacting with AlgR, and that it may have
      negative effects on expression of the mucoid phenotype under the conditions
      tested. The presented results suggest that elements of negative regulation exist
      at the levels of both the alternative sigma factor AlgU and the transcriptional
      activator AlgR which, once relieved from that suppression, cooperate to bring
      about the expression of the alginate system.

PMID- 8981998
TI  - Bradyrhizobium japonicum does not require alpha-ketoglutarate dehydrogenase for
      growth on succinate or malate.
AB  - The sucA gene, encoding the E1 component of alpha-ketoglutarate dehydrogenase,
      was cloned from Bradyrhizobium japonicum USDA110, and its nucleotide sequence was
      determined. The gene shows a codon usage bias typical of non-nif and non-fix
      genes from this bacterium, with 89.1% of the codons being G or C in the third
      position. A mutant strain of B. japonicum, LSG184, was constructed with the sucA
      gene interrupted by a kanamycin resistance marker. LSG184 is devoid of alpha
      ketoglutarate dehydrogenase activity, indicating that there is only one copy of
      sucA in B. japonicum and that it is completely inactivated in the mutant. Batch
      culture experiments on minimal medium revealed that LSG184 grows well on a
      variety of carbon substrates, including arabinose, malate, succinate, beta
      hydroxybutyrate, glycerol, formate, and galactose. The sucA mutant is not a
      succinate auxotroph but has a reduced ability to use glutamate as a carbon or
      nitrogen source and an increased sensitivity to growth inhibition by acetate,
      relative to the parental strain. Because LSG184 grows well on malate or succinate
      as its sole carbon source, we conclude that B. japonicum, unlike most other
      bacteria, does not require an intact tricarboxylic acid (TCA) cycle to meet its
      energy needs when growing on the four-carbon TCA cycle intermediates. Our data
      support the idea that B. japonicum has alternate energy-yielding pathways that
      could potentially compensate for inhibition of alpha-ketoglutarate dehydrogenase
      during symbiotic nitrogen fixation under oxygen-limiting conditions.

PMID- 8981999
TI  - Purification and characterization of 2,4,6-trichlorophenol-4-monooxygenase, a
      dehalogenating enzyme from Azotobacter sp. strain GP1.
AB  - The enzyme which catalyzes the dehalogenation of 2,4,6-trichlorophenol (TCP) was
      purified to apparent homogeneity from an extract of TCP-induced cells of
      Azotobacter sp. strain GP1. The initial step of TCP degradation in this bacterium
      is inducible by TCP; no activity was found in succinate-grown cells or in phenol
      induced cells. NADH, flavin adenine dinucleotide, and O2 are required as
      cofactors. As reaction products, 2,6-dichlorohydroquinone and Cl- ions were
      identified. Studies of the stoichiometry revealed the consumption of 2 mol of
      NADH plus 1 mol of O2 per mol of TCP and the formation of 1 mol of Cl- ions. No
      evidence for membrane association or for a multicomponent system was obtained.
      Molecular masses of 240 kDa for the native enzyme and 60 kDa for the subunit were
      determined, indicating a homotetrameric structure. Cross-linking studies with
      dimethylsuberimidate were consistent with this finding. TCP was the best
      substrate for 2,4,6-trichlorophenol-4-monooxygenase (TCP-4-monooxygenase). The
      majority of other chlorophenols converted by the enzyme bear a chloro substituent
      in the 4-position. 2,6-Dichlorophenol, also accepted as a substrate, was
      hydroxylated in the 4-position to 2,6-dichlorohydroquinone in a nondehalogenating
      reaction. NADH and O2 were consumed by the pure enzyme also in the absence of TCP
      with simultaneous production of H2O2. The NH2-terminal amino acid sequence of TCP
      4-monooxygenase from Azotobacter sp. strain GP1 revealed complete identity with
      the nucleotide-derived sequence from the analogous enzyme from Pseudomonas
      pickettii and a high degree of homology with two nondehalogenating
      monooxygenases. The similarity in enzyme properties and the possible evolutionary
      relatedness of dehalogenating and nondehalogenating monooxygenases are discussed.

PMID- 8982000
TI  - Genetic analysis of the Rhizobium meliloti bacA gene: functional
      interchangeability with the Escherichia coli sbmA gene and phenotypes of mutants.
AB  - The Rhizobium meliloti bacA gene encodes a function that is essential for
      bacterial differentiation into bacteroids within plant cells in the symbiosis
      between R. meliloti and alfalfa. An Escherichia coli homolog of BacA, SbmA, is
      implicated in the uptake of microcin B17, microcin J25 (formerly microcin 25),
      and bleomycin. When expressed in E. coli with the lacZ promoter, the R. meliloti
      bacA gene was found to suppress all the known defects of E. coli sbmA mutants,
      namely, increased resistance to microcin B17, microcin J25, and bleomycin,
      demonstrating the functional similarity between the two proteins. The R. meliloti
      bacA386::Tn(pho)A mutant, as well as a newly constructed bacA deletion mutant,
      was found to show increased resistance to bleomycin. However, it also showed
      increased resistance to certain aminoglycosides and increased sensitivity to
      ethanol and detergents, suggesting that the loss of bacA function causes some
      defect in membrane integrity. The E. coli sbmA gene suppressed all these bacA
      mutant phenotypes as well as the Fix- phenotype when placed under control of the
      bacA promoter. Taken together, these results strongly suggest that the BacA and
      SbmA proteins are functionally similar and thus provide support for our previous
      hypothesis that BacA may be required for uptake of some compound that plays an
      important role in bacteroid development. However, the additional phenotypes of
      bacA mutants identified in this study suggest the alternative possibility that
      BacA may be needed for membrane integrity, which is likely to be critically
      important during the early stages of bacterial differentiation within plant
      cells.

PMID- 8982002
TI  - Functional characterization of roles of GalR and GalS as regulators of the gal
      regulon.
AB  - An isorepressor of the gal regulon in Escherichia coli, GalS, has been purified
      to homogeneity. In vitro DNase I protection experiments indicated that among
      operators of the gal regulon, GalS binds most strongly to the external operator
      of the mgl operon, which encodes the high-affinity beta-methylgalactoside
      galactose transport system, and with less affinity to the operators controlling
      expression of the gal operon, which codes for enzymes of galactose metabolism.
      GalS has even less affinity for the external operator of galP, which codes for
      galactose permease, the major low-affinity galactose transporter in the cell.
      This order of affinities is the reverse of that of GalR, which binds most
      strongly to the operator of galP and most weakly to that of mgl. Our results also
      show that GalS, like its homolog, GalR, is a dimeric protein which in binding to
      the bipartite operators of the gal operon selectively represses its P1 promoter.
      Consistent with the fact that GalR is the exclusive regulator of the low-affinity
      galactose transporter, galactose permease, and that the major role of GalS is in
      regulating expression of the high-affinity galactose transporter encoded by the
      mgl operon, we found that the DNA binding of GalS is 15-fold more sensitive than
      that of GalR to galactose.

PMID- 8982001
TI  - Homology throughout the multiple 32-kilobase circular plasmids present in Lyme
      disease spirochetes.
AB  - We have characterized seven different 32-kb circular plasmids carried by Borrelia
      burgdorferi isolate B31. Restriction endonuclease recognition site mapping and
      partial sequencing of these plasmids indicated that all seven are probably
      closely related to each other throughout their lengths and have substantial
      relationships to cp8.3, an 8.3-kb circular plasmid of B. burgdorferi sensu lato
      isolate Ip21. With the addition of the seven 32-kb plasmids, this bacterial
      strain is known to carry at least 10 linear and 9 circular plasmids. Variant
      cultures of B. burgdorferi B31 lacking one or more of the 32-kb circular plasmids
      are viable and, at least in some cases, infectious. We have examined a number of
      different natural isolates of Lyme disease borreliae and found that all of the B.
      burgdorferi sensu stricto isolates and most of the B. burgdorferi sensu lato
      isolates tested appear to carry multiple 32-kb circular plasmids related to those
      of B. burgdorferi B31. The ubiquity of these plasmids suggests that they may be
      important in the natural life cycle of these organisms. They may be highly
      conjugative plasmids or prophage genomes, which could prove to be useful in
      genetically manipulating B. burgdorferi.

PMID- 8982004
TI  - Purification of Vibrio cholerae fur and estimation of its intracellular abundance
      by antibody sandwich enzyme-linked immunosorbent assay.
AB  - The Vibrio cholerae fur gene was previously cloned and sequenced. A putative Fur
      box was identified in the divergent promoters of irgA, a virulence factor of V.
      cholerae, and irgB, a transcriptional activator of irgA. In this work, V.
      cholerae Fur was overexpressed in Escherichia coli and purified to approximately
      95% homogeneity. The purified protein bound a DNA fragment containing the irgA
      irgB promoter in a gel shift assay. The purified protein was used to raise
      monoclonal and polyclonal antibodies to V. cholerae Fur, and a Fur sandwich
      enzyme-linked immunosorbent assay was developed to estimate the intracellular
      abundance of Fur under a variety of growth conditions. The number of Fur
      molecules per cell during exponential growth was approximately 2,500, which is
      higher than most measurements for other bacterial repressors but comparable to
      the intracellular concentration of the leucine-responsive regulatory protein. The
      number of Fur molecules per cell increased in the late logarithmic and stationary
      phases. Growth of V. cholerae in low-iron medium did not alter the intracellular
      abundance of Fur significantly. Growth under microaerophilic conditions resulted
      in a significant, approximately twofold decrease in the intracellular levels of
      Fur. The measurements of intracellular Fur abundance indicate that a large amount
      of this repressor is produced constitutively and that the concentration of Fur in
      the cell varies by less than a factor of 2 under the conditions studied. We
      hypothesize that the high constitutive expression of Fur is necessary for its
      role as an iron-responsive regulator.

PMID- 8982003
TI  - Gene cluster for dissimilatory nitrite reductase (nir) from Pseudomonas
      aeruginosa: sequencing and identification of a locus for heme d1 biosynthesis.
AB  - The primary structure of an nir gene cluster necessary for production of active
      dissimilatory nitrite reductase was determined from Pseudomonas aeruginosa. Seven
      open reading frames, designated nirDLGHJEN, were identified downstream of the
      previously reported nirSMCF genes. From nirS through nirN, the stop codon of one
      gene and the start codon of the next gene were closely linked, suggesting that
      nirSMCFDLGHJEN are expressed from a promoter which regulates the transcription of
      nirSM. The amino acid sequences deduced from the nirDLGH genes were homologous to
      each other. A gene, designated nirJ, which encodes a protein of 387 amino acids,
      showed partial identity with each of the nirDLGH genes. The nirE gene encodes a
      protein of 279 amino acids homologous to S-adenosyl-L-methionine:uroporphyrinogen
      III methyltransferase from other bacterial strains. In addition, NirE shows 21.0%
      identity with NirF in the N-terminal 100-amino-acid residues. A gene, designated
      nirN, encodes a protein of 493 amino acids with a conserved binding motif for
      heme c (CXXCH) and a typical N-terminal signal sequence for membrane
      translocation. The derived NirN protein shows 23.9% identity with nitrite
      reductase (NirS). Insertional mutation and complementation analyses showed that
      all of the nirFDLGHJE genes were necessary for the biosynthesis of heme d1.

PMID- 8982005
TI  - Biosynthesis of pyochelin and dihydroaeruginoic acid requires the iron-regulated
      pchDCBA operon in Pseudomonas aeruginosa.
AB  - The high-affinity siderophore salicylate is an intermediate in the biosynthetic
      pathway of pyochelin, another siderophore and chelator of transition metal ions,
      in Pseudomonas aeruginosa. The 2.5-kb region upstream of the salicylate
      biosynthetic genes pchBA was sequenced and found to contain two additional,
      contiguous genes, pchD and pchC, having the same orientation. The deduced amino
      acid sequence of the 60-kDa PchD protein was similar to those of the EntE protein
      (2,3-dihydroxybenzoate-AMP ligase) of Escherichia coli and other adenylate
      forming enzymes, suggesting that salicylate might be adenylated at the carboxyl
      group by PchD. The 28-kDa PchC protein showed similarities to thioesterases of
      prokaryotic and eukaryotic origin and might participate in the release of the
      product(s) formed from activated salicylate. One potential product,
      dihydroaeruginoate (Dha), was identified in culture supernatants of iron-limited
      P. aeruginosa cells. The antifungal antibiotic Dha is thought to arise from the
      reaction of salicylate with cysteine, followed by cyclization of cysteine.
      Inactivation of the chromosomal pchD gene by insertion of the transcription and
      translation stop element omega Sm/Sp abolished the production of Dha and
      pyochelin, implying that PchD-mediated activation of salicylate may be a common
      first step in the synthesis of both metabolites. Furthermore, the pchD::omega
      Sm/Sp mutation had a strong polar effect on the expression of the pchBA genes,
      i.e., on salicylate synthesis, indicating that the pchDCBA genes constitute a
      transcriptional unit. A full-length pchDCBA transcript of ca. 4.4 kb could be
      detected in iron-deprived, growing cells of P. aeruginosa. Transcription of pchD
      started at tandemly arranged promoters, which overlapped with two Fur boxes
      (binding sites for the ferric uptake regulator) and the promoter of the
      divergently transcribed pchR gene encoding an activator of pyochelin
      biosynthesis. This promoter arrangement allows tight iron-mediated repression of
      the pchDCBA operon.

PMID- 8982006
TI  - Nitrogen deprivation of Anabaena sp. strain PCC 7120 elicits rapid activation of
      a gene cluster that is essential for uptake and utilization of nitrate.
AB  - A transposon bearing luxAB, encoding luciferase, as a reporter of transcription
      was used to identify genes that are activated rapidly upon deprivation of
      Anabaena sp. strain PCC 7120 of fixed nitrogen. The three transposon-marked loci
      that were identified as responding most rapidly and strongly are closely linked
      and situated within nirA and nrtC and between nrtD and narB, genes whose products
      are responsible for uptake and reduction of NO2- and NO3-. A strain bearing a
      transcriptional fusion of narB to luxAB was constructed. Luminescence catalyzed
      by LuxAB was used to report on the expression of the interrupted genes. Whether
      these genes are regulated only coordinately is discussed.

PMID- 8982007
TI  - Anabaena sp. strain PCC 7120 responds to nitrogen deprivation with a cascade-like
      sequence of transcriptional activations.
AB  - Anabaena sp. strain PCC 7120 adapts to deprivation of fixed nitrogen by
      undergoing physiological and genetic changes that include formation of N2-fixing
      heterocysts. Whether or not certain of the genes involved are interdependently
      expressed has been studied.

PMID- 8982008
TI  - Effects of inactivation or overexpression of the sspF gene on properties of
      Bacillus subtilis spores.
AB  - Inactivation of the Bacillus subtilis sspF gene had no effect on sporulation,
      spore resistance, or germination in a wild-type strain or one lacking DNA
      protective alpha/beta-type small, acid-soluble proteins (SASP). Overexpression of
      SspF in wild-type spores or in spores lacking major alpha/beta-type SASP (alpha-
      beta- spores) had no effect on sporulation but slowed spore outgrowth and
      restored a small amount of UV and heat resistance to alpha- beta- spores. In
      vitro analyses showed that SspF is a DNA binding protein and is cleaved by the
      SASP-specific protease (GPR) at a site similar to that cleaved in alpha/beta-type
      SASP. SspF was also degraded during spore germination and outgrowth, and this
      degradation was initiated by GPR.

PMID- 8982011
TI  - In vivo expression of the Lactobacillus brevis S-layer gene.
AB  - Lactobacillus brevis possesses a surface layer protein (SlpA) with tightly
      regulated synthesis. The slpA gene is expressed by two adjacent promoters, P1 and
      P2. The level of P2-derived transcripts was approximately 10 times higher than
      that of P1-derived transcripts throughout the entire growth of L. brevis. The
      half-lives of slpA transcripts were shown to be exceptionally long (14 min).

PMID- 8982010
TI  - A 53-base-pair inverted repeat negatively regulates expression of the adjacent
      and divergently oriented cytochrome P450(BM-1) gene and its regulatory gene,
      bm1P1, in Bacillus megaterium.
AB  - To study the role of the cis-acting element(s) in controlling the expression of
      the cytochrome P450(BM-1) gene and its upstream regulatory gene, bm1P1, in
      Bacillus megaterium, various deletion derivatives were constructed. A 53-bp
      inverted repeat located midway between the P450(BM-1) gene and bm1P1 gene was
      found in vivo to negatively regulate the expression of both genes, the regulation
      of which may occur at the transcriptional level. The promoter of the P450(BM-1),
      gene was also identified and found to be similar to those recognized by the
      sigmaA RNA polymerase of Bacillus subtilis. Possible mechanisms by which the 53
      bp inverted repeat regulates the gene expression are discussed.

PMID- 8982009
TI  - Binding of L-branched-chain amino acids causes a conformational change in BkdR.
AB  - BkdR is the positive transcriptional activator of the inducible bkd operon of
      Pseudomonas putida. Evidence is accumulating that L-branched-chain amino acids
      are the inducers of the operon, and the data obtained in this study show that
      they induce a conformational change in BkdR. Addition of L-branched-chain amino
      acids increased the susceptibility of BkdR to trypsin with the cleavage between
      Arg-51 and Gln-52 on the C-terminal side of the DNA-binding domain. L-Valine also
      caused an increased fluorescence emission intensity and produced significant
      changes in the circular dichroism spectrum of BkdR. Analytical
      ultracentrifugation confirmed earlier data obtained from gel filtration that BkdR
      was a tetramer with a Stokes radius of 32 +/- 3 A and an axial ratio of 2:1.

PMID- 8982012
TI  - Phosphorylating and dephosphorylating protein complexes in bacterial chemotaxis.
AB  - During optimal motility conditions, a 1:1 stoichiometry of CheA(L) (654 amino
      acids) to CheA(S) (557 amino acids) was determined. It was also found that CheZ
      binding to CheA(S) was inhibited by CheA(L)-CheA(S)-CheW interaction. This
      suggests that CheA(S) has different functions in the phosphorylating complex
      (CheA(L)-CheA(S)-CheW) and in the dephosphorylating complex (CheA(S)-CheZ).

PMID- 8982013
TI  - HupUV proteins of Rhodobacter capsulatus can bind H2: evidence from the H-D
      exchange reaction.
AB  - The H-D exchange reaction has been measured with the D2-H2O system, for
      Rhodobacter capsulatus JP91, which lacks the hupSL-encoded hydrogenase, and R.
      capsulatus BSE16, which lacks the HupUV proteins. The hupUV gene products,
      expressed from plasmid pAC206, are shown to catalyze an H-D exchange reaction
      distinguishable from the H-D exchange due to the membrane-bound, hupSL-encoded
      hydrogenase. In the presence of O2, the uptake hydrogenase of BSE16 cells
      catalyzed a rapid uptake and oxidation of H2, D2, and HD present in the system,
      and its activity (H-D exchange, H2 evolution in presence of reduced methyl
      viologen [MV+]) depended on the external pH, while the H-D exchange due to HupUV
      remained insensitive to external pH and O2. These data suggest that the HupSL
      dimer is periplasmically oriented, while the HupUV proteins are in the
      cytoplasmic compartment.

PMID- 8982014
TI  - Identification, sequencing, and enzymatic activity of the erythrose-4-phosphate
      dehydrogenase gene of Vibrio cholerae.
AB  - We have identified a gene in Vibrio cholerae (epd) which encodes an erythrose-4
      phosphate dehydrogenase activity and is located immediately downstream of an iron
      regulated virulence gene, irgA, and immediately upstream of a gene encoding
      phosphoglycerate kinase (pgk). Expression of epd in V. cholerae is not regulated
      by iron, nor is it required for virulence in an infant mouse model.

PMID- 8982015
TI  - The RNA-binding protein HF-I plays a global regulatory role which is largely, but
      not exclusively, due to its role in expression of the sigmaS subunit of RNA
      polymerase in Escherichia coli.
AB  - The hfq-encoded RNA-binding protein HF-I has long been known as a host factor for
      phage Qbeta RNA replication and has recently been shown to be essential for
      translation of rpoS, which encodes the sigmaS subunit of RNA polymerase. Here we
      demonstrate that an hfq null mutant does not synthesize glycogen, is starvation
      and multiple stress sensitive, and exhibits strongly reduced expression of
      representative sigmaS-regulated genes. These phenotypes are consistent with
      strongly reduced sigmaS levels in the hfq mutant. However, the analysis of global
      protein synthesis patterns on two-dimensional O'Farrell gels indicates that
      approximately 40% of the more than 30 proteins whose syntheses are altered in the
      hfq null mutant are not affected by an rpoS mutation. We conclude that HF-I is a
      global regulator involved in the regulation of expression of sigmaS and sigmaS
      independent genes.

PMID- 8982016
TI  - Cancer incidence near radio and television transmitters in Great Britain. I.
      Sutton Coldfield transmitter.
AB  - A small area study of cancer incidence in 1974-1986 was carried out to
      investigate an unconfirmed report of a "cluster" of leukemias and lymphomas near
      the Sutton Coldfield television (TV) and frequency modulation (FM) radio
      transmitter in the West Midlands, England. The study used a national database of
      postcoded cancer registrations, and population and socioeconomic data from the
      1981 census. Selected cancers were hematopoietic and lymphatic, brain, skin, eye,
      male breast, female breast, lung, colorectal, stomach, prostate, and bladder.
      Expected numbers of cancers in small areas were calculated by indirect
      standardization, with stratification for a small area socioeconomic index. The
      study area was defined as a 10 km radius circle around the transmitter, within
      which 10 bands of increasing distance from the transmitter were defined as a
      basis for testing for a decline in risk with distance, and an inner area was
      arbitrarily defined for descriptive purposes as a 2 km radius circle. The risk of
      adult leukemia within 2 km was 1.83 (95% confidence interval 1.22-2.74), and
      there was a significant decline in risk with distance from the transmitter (p =
      0.001). These findings appeared to be consistent over the periods 1974-1980, 1981
      1986, and were probably largely independent of the initially reported cluster,
      which appeared to concern mainly a later period. In the context of variability of
      leukemia risk across census wards in the West Midlands as a whole, the Sutton
      Coldfield findings were unusual. A significant decline in risk with distance was
      also found for skin cancer, possibly related to residual socioeconomic
      confounding, and for bladder cancer. Study of other radio and TV transmitters in
      Great Britain is required to put the present results in wider context. No causal
      implications can be made from a single cluster investigation of this kind.

PMID- 8982017
TI  - Cancer incidence near radio and television transmitters in Great Britain. II. All
      high power transmitters.
AB  - A small area study of cancer incidence, 1974-1986, near 20 high power television
      (TV) and frequency modulation (FM) radio transmitters in Great Britain was
      carried out to place in context the findings of an earlier study around the
      Sutton Coldfield transmitter. The national database of postcoded cancer
      registrations was used with population and socioeconomic data from the 1981
      census. Cancers examined were adult leukemias, skin melanoma, and bladder cancer,
      following the findings in the earlier study of significant declines in risk of
      these cancers with distance from the Sutton Coldfield transmitter. Childhood
      leukemia and brain cancer were also examined. Statistical analysis was performed
      for all transmitters combined, four overlapping groups of transmitters defined by
      their transmission characteristics, and for all transmitters separately. There
      were 3,305 adult leukemia cases from 0-10 km (observed/expected (O/E) ratio =
      1.03, 95% confidence interval (CI) 1.00-1.07). A decline in risk of adult
      leukemia was found for all transmitters combined (p = 0.05), two of the
      transmitter groups, and three of the single transmitters; for all transmitters
      combined, observed excess risk was no more than 15% at any distance up to 10 km,
      and there was no observed excess within 2 km of transmitters (O/E ratio = 0.97,
      95% CI 0.78-1.21). For childhood leukemia and brain cancer, and adult skin
      melanoma and bladder cancer, results were not indicative of a decline in risk
      with distance from transmitters. The magnitude and pattern of risk found in the
      Sutton Coldfield study did not appear to be replicated. The authors conclude that
      the results at most give no more than very weak support to the Sutton Coldfield
      findings.

PMID- 8982018
TI  - Fasting insulin level underestimates risk of non-insulin-dependent diabetes
      mellitus due to confounding by insulin secretion.
AB  - Fasting insulin has been used as a surrogate measure of insulin sensitivity in
      studies of non-insulin-dependent diabetes mellitus (NIDDM) risk, but the fasting
      insulin-NIDDM association may be confounded by insulin secretion, which
      correlates negatively with NIDDM risk and positively with fasting insulin level.
      In a prospective 5-year study of 137 nondiabetic Japanese-American men in King
      County, Washington State, higher fasting insulin was not strongly related to
      NIDDM (odds ratio (OR) = 1.37, 95% confidence interval (CI) 0.80-2.34), but this
      odds ratio increased substantially after adjustment for insulin secretion (OR =
      2.92, 95% CI 1.41-6.06). Research on NIDDM risk in relation to fasting insulin
      may yield biased effect measures unless adjusted for insulin secretion.

PMID- 8982019
TI  - Diabetes mellitus, impaired glucose tolerance, and hyperinsulinemia in an elderly
      population. The Rotterdam Study.
AB  - To estimate the prevalence of glucose intolerance in the elderly, oral glucose
      tolerance tests were performed as part of the Rotterdam Study, a population-based
      study in subjects aged 55 years and over. The study population consisted of 2,668
      men and 3,950 women. Diabetes mellitus was defined as the use of antidiabetes
      medication, or a random or post-load serum glucose level of > or = 11.1
      mmol/liter. Impaired glucose tolerance was defined as a post-load serum glucose
      between 7.8 and 11.1 mmol/liter. In men, the frequency of diabetes mellitus
      ranged from 5.9% in ages < 60 years to 19.8% in ages > 85 years, and in women
      from 3.8% in ages < 60 years to 18.9% in ages > 85 years; more than half of the
      subjects with diabetes were newly diagnosed. The prevalence of impaired glucose
      tolerance ranged from 8.8% and 11.0% in men and women aged < 60 years to 24.3%
      and 34.7% in men and women aged > 85 years. The prevalence of diabetes mellitus
      in the total Rotterdam Study population of 7,439 elderly men and women was
      estimated to be 11.3% (95% confidence interval (CI) 10.5-12.0). Waist/hip ratio,
      systolic blood pressure, hypertension, and number of cigarettes smoked increased
      with a worsening of the glucose tolerance from normal, hyperinsulinemia, impaired
      glucose tolerance to diabetes in both men and women (p < 0.01, adjusted for age).
      Body mass index was higher in subjects with glucose intolerance, but the
      frequency of obesity showed a relative decrease with worsening of glucose
      tolerance. These results show that glucose intolerance, especially impaired
      glucose tolerance and undetected diabetes mellitus, is common in the elderly.
      Moreover, not only subjects with diabetes mellitus but also subjects with
      hyperinsulinemia and impaired glucose tolerance have an increase of
      cardiovascular risk factors.

PMID- 8982020
TI  - Polyunsaturated fatty acids, antioxidants, and cognitive function in very old
      men.
AB  - Atherosclerosis and thrombosis may lead to cognitive impairment through cerebral
      infarcts or white matter hyperintensities. Oxidative stress is now seen as a
      major contributor to the process of atherogenesis. High intake of polyunsaturated
      fatty acids, e.g., linoleic acid, or low intake of antioxidants can increase
      oxidative stress. High intake of n-3 polyunsaturated fatty acids and its main
      source, fish, may reduce the risk of thrombosis. Little is known, however, about
      the relation between these dietary factors and cognitive function. The authors
      investigated this relation with data derived from a cohort of men, aged 69-89
      years, who were participants in the Zutphen Elderly Study. The 30-point Mini
      Mental State Examination was used to assess cognitive impairment in 1990 (score <
      or = 25 in 153/476 men, 32%) and cognitive decline from 1990 to 1993 (drop > 2
      points in 51/342 men, 15%). Food intake was estimated in 1985 and 1990 by the
      cross-check dietary history method. High linoleic acid intake was associated with
      cognitive impairment after adjustment for age, education, cigarette smoking,
      alcohol consumption, and energy intake (odds ratio (OR) for highest vs. lowest
      tertile = 1.76, 95% confidence interval (CI) 1.04-3.01). Intake of n-3
      polyunsaturated fatty acids was not associated with cognitive impairment, whereas
      high fish consumption tended to be inversely associated with cognitive impairment
      (OR = 0.63, 95% CI 0.33-1.21) and cognitive decline (OR = 0.45, 95% CI 0.17
      1.16). Intakes of beta-carotene, vitamins C and E, and flavonoids were not
      inversely associated with cognitive impairment or decline. This study raises the
      possibility that high linoleic acid intake is positively associated with
      cognitive impairment and high fish consumption inversely associated with
      cognitive impairment.

PMID- 8982021
TI  - Prospective study of diet and the risk of duodenal ulcer in men.
AB  - The authors examined the associations between dietary factors and the risk of
      duodenal ulcer in a prospective cohort of 47,806 men, aged 40-75 years, who were
      free of diagnosed gastric or duodenal ulcer or cancer. During 6 years of follow
      up, they documented 138 newly diagnosed cases of duodenal ulcer. They found
      little evidence for an important effect of fat, type of fat, or protein intake.
      Higher consumption of fruits and vegetables was associated with lower risk of
      duodenal ulcer (relative risk (RR) = 0.67, 95% confidence interval (CI) 0.39-1.15
      for > or = 7 servings per day vs. < 3 servings per day) after adjustment for age,
      body mass index, smoking, and use of aspirin or other nonsteroidal anti
      inflammatory drugs. Total dietary fiber intake was inversely associated with the
      risk of duodenal ulcer (RR = 0.55, 95% CI 0.31-0.96 for men in the highest vs.
      the lowest quintile of dietary fiber). The soluble component of fiber was
      strongly associated with a decreased risk of duodenal ulcer (RR = 0.40, 95% CI
      0.22-0.74 for the highest quintile). Several age- and energy-adjusted nutrients
      correlated with dietary fiber were also inversely related to the risk of duodenal
      ulcer, but vitamin A from all sources combined (including supplements and
      multivitamins) was the only nutrient that was statistically significant after
      adjustment for other risk factors (RR = 0.46, 95% CI 0.23-0.91 for men in the
      highest vs. the lowest quintile of vitamin A intake). These findings provide
      evidence that vitamin A from all sources, as well as diets high in fruits and
      vegetables, may reduce the development of duodenal ulcer, possibly due to their
      fiber content. Although the associations appeared stronger for dietary fiber and
      vitamin A, the authors can not exclude the possibility that other closely
      correlated dietary factors may be the true protective factors.

PMID- 8982022
TI  - Decline in measles case fatality ratio after the introduction of measles
      immunization in rural Senegal.
AB  - The epidemiology of measles has been investigated in Niakhar, a rural area of
      Senegal, during two periods, 1983-1986 and 1987-1990. Following a major increase
      in immunization coverage beginning in 1987, the case fatality ratio for all ages
      declined fourfold from the first to the second period (relative risk (RR) = 0.24,
      95% confidence interval (CI) 0.13-0.46). The measles incidence for children under
      10 years of age declined by 69% (95% CI 65-72) and the risk of dying of measles
      by 91% (95% CI 82-95). Vaccinated children who contracted measles had
      significantly lower case fatality ratio than unvaccinated children with measles
      (p = 0.038). Children infected by an immunized case tended to have lower case
      fatality ratio than those infected by an unimmunized index case (p = 0.104) and
      immunized index cases generated fewer secondary cases than unimmunized index
      cases (p < 0.001). Respiratory complications were more common in secondary cases
      infected by an index case with respiratory complications than by an index case
      without such complications (RR = 1.60, 95% CI 1.08-2.37), which suggests that
      severe cases give rise to further severe cases. As expected, there was a
      significant increase in the proportion of vaccinated cases in the second period
      (RR = 1.41, 95% CI 1.00-1.98). Mean age at infection increased from 4 to 7 years
      between the two periods and the change in age structure accounted for 20% of the
      decline in case fatality ratio. Measles immunization may contribute to lower
      mortality directly through reduced incidence and indirectly through increases in
      age at infection, less severe infection for immunized cases and changes in
      transmission patterns leading to reduced severity of measles.

PMID- 8982023
TI  - Medical record validation of maternally reported birth characteristics and
      pregnancy-related events: a report from the Children's Cancer Group.
AB  - Epidemiologic studies frequently obtain exposure information through subjects'
      self-report (personal interview or mailed questionnaire). The authors used data
      from a case-control study of infant leukemia, to assess the validity and
      reliability of maternally reported information on birth characteristics such as
      birth weight, reproductive history, and medical procedures. Cases were gathered
      from the Children's Cancer Group, a United States and Canadian cooperative
      clinical trails group with approximately 100 member and affiliate institutions,
      during 1983-1988. Telephone interviews were completed for 302 cases and 558
      matched controls. Medical records of the index pregnancy were obtained for 287
      cases and 467 controls. Correlations between medical charts and maternal
      interview were high for birth weight (r = 0.98, kappa = 0.9) and gestational age
      (r = 0.86, kappa = 0.6). Mean differences between the two sources were small, 
      10.5 g for birth weight and -0.36 weeks for gestational age. Reproductive history
      and medical procedures had high to moderate reliability. Problems after delivery
      and pregnancy complications generally had low validity and reliability. Little
      evidence of differential misclassification was found. Time between delivery and
      interview ranged from zero to 8 years and did not greatly affect reliability.
      This study suggests that validity and reliability of maternally reported
      pregnancy and delivery information may differ with the nature of the factor of
      interest, but is affected little by time from birth or case-control status.

PMID- 8982024
TI  - Accuracy of birth certificate data regarding the amount, timing, and adequacy of
      prenatal care using prenatal clinic medical records as referents.
AB  - This study compared birth certificate data on the amount, timing, and adequacy of
      prenatal care with the same data abstracted from the prenatal clinic records of
      2,032 women who attended a health department prenatal clinic in northeast Georgia
      from 1980 to 1988. Overall accuracy was poor. Only 14.3% (n = 291) of the records
      completely agreed on the total number of visits, while approximately 36% (n =
      738) and 53% (n = 1,081) agreed within one visit and two visits, respectively.
      Complete agreement for month and trimester prenatal care began was 31.1% (n =
      632) and 50.6% (n = 1,202), respectively. Because of the small geographic region
      included in the current study, the generalizability of these findings to other
      populations may be limited.

PMID- 8982025
TI  - Time-to-event analysis of longitudinal follow-up of a survey: choice of the time
      scale.
AB  - Following individuals sampled in a large-scale health survey for the development
      of diseases and/or death offers the opportunity to assess the prognostic
      significance of various risk factors. The proportional hazards regression model,
      which allows for the control of covariates, is frequently used for the analysis
      of such data. The authors discuss the appropriate time-scale for such regression
      models, and they recommend that age rather than time since the baseline survey
      (time-on-study) be used. Additionally, with age as the time-scale, control for
      calendar-period and/or birth cohort effects can be achieved by stratifying the
      model on birth cohort. Because, as discussed by the authors, many published
      analyses have used regression models with time-on-study as the time-scale, it is
      important to assess the magnitude of the error incurred from this type of
      incorrect modeling. The authors provide simple conditions for when incorrect use
      of time-on-study as the time-scale will nevertheless yield approximately unbiased
      proportional hazards regression coefficients. Examples are given using data from
      the first National Health and Nutrition Examination Survey (NHANES I)
      Epidemiologic Followup Study. Additional issues concerning the analysis of
      longitudinal follow-up of survey data are briefly discussed.

PMID- 8982026
TI  - Re: "Smoking reduces fecundity: a European multicenter study on infertility and
      subfecundity".

PMID- 8982027
TI  - Re: "How useful is body mass index for comparison of body fatness across age,
      sex, and ethnic groups?".

PMID- 8982028
TI  - Re: "Sex-specific associations of magnetic resonance imaging-derived intra
      abdominal and subcutaneous fat areas with conventional anthropometric indices:
      the Atherosclerosis in Communities Study".

PMID- 8982029
TI  - Re: "Multiple comparisons and related issues in the interpretation of
      epidemiologic data".

PMID- 8982030
TI  - The population genetics of factor V Leiden (Arg506Gln)

PMID- 8982031
TI  - Extended multidrug resistance in haemopoietic cells.
AB  - The development of drug resistance was studied in a series of haemopoietic cells
      to determine its relationship to cell lineage. Treatment of the U937 monocytic
      cell line with epirubicin (15 ng/ml) or vinblastine (8 ng/ml) induced drug
      resistant sublines with cross-resistance to epirubicin (8- and 16-fold
      respectively), vinblastine (5- and 20-fold), paclitaxel (15- and 42-fold) and
      etoposide (19- and 13-fold). However, sublines were also 3-5-fold resistant to
      the alkylating agent chlorambucil, cis-platinum and methotrexate, demonstrating
      an extended multidrug resistance (MDR) phenotype. These cells over-expressed P
      glycoprotein, but decreased drug accumulation was not restored in the presence of
      verapamil, suggesting that the P-glycoprotein was not functional. Similar drug
      treatment of the HL60 promyelocytic cell line also produced sublines exhibiting
      an extended MDR phenotype. The KG1a and the HEL cell lines expressed functional P
      glycoprotein and were resistant to the drug concentrations used for treatment.
      Multidrug resistance as mediated by P-glycoprotein cannot explain the resistance
      of CML patients to chemotherapy, especially in blast crisis. The induction of an
      extended MDR phenotype specifically in myeloid cells in response to drug
      treatment may explain the resistance observed in the treatment of CMI.

PMID- 8982032
TI  - Murine marrow stromal response to myelotoxic agents in vitro.
AB  - Previous studies have shown that the haemopoietically active murine long-term
      bone marrow culture (LTBMC) is a useful model for studying drug-induced
      suppression and recovery of myelopoiesis. We studied the effects on stromal
      morphology and stromal progenitors, assessed as colony forming unit-fibroblasts
      (CFU-F), of the addition of either the antimetabolite methotrexate (MTX) or the
      betalactam ceftazidime (CEF) to LTBMC. The examination of 500 micrograms/ml CEF
      treated cultures revealed a stroma that appeared empty, with modest reduction in
      total stromal counts, and significant decreases in fat-containing and endothelial
      cells. In contrast, treatment with 1 microM MTX for 1 week initially caused
      minimal morphologic stromal changes, thereafter total stromal cell count as well
      as fibroblastoid, endothelial, fat containing and macrophage cells significantly
      increased. Haemopoiesis and the stroma recovered. Both CEF and MTX reversibly
      suppressed stromal progenitor cells in LTBMC. When added directly to CFU-F
      cultures, the concentrations resulting in a 50% colony growth inhibition were 214
      micrograms/ml for CEF and 375 nM for MTX. These results suggest that CEF, but not
      MTX, has direct toxic effects on the stroma of established LTBMC. Stromal cell
      increase following MTX treatment probably indicates a stromal response that may
      contribute to haemopoietic cell recovery.

PMID- 8982033
TI  - Serum thrombopoietin levels in patients with aplastic anaemia.
AB  - Endogenous serum thrombopoietin (TPO) levels were measured in 31 patients with
      aplastic anaemia (AA) using an enzyme immunoassay with a sensitivity of 20 pg/
      ml. The median platelet count for all AA patients was 30 +/- 29 x 10(9)/l (range
      5-102) compared with a median of 284 +/- 59 x 10(9)/l (range 148-538) for normal
      controls. Serum TPO levels were significantly elevated in all patients compared
      with normals (1706 +/- 1114.2, range 375-5000 v 78 +/- 54, range 16.5-312.9, P <
      0.0001). There was no correlation between serum TPO levels and the degree of
      thrombocytopenia in AA patients, but TPO levels were significantly higher in
      patients who were platelet transfusion dependent than in patients who were
      transfusion independent (P < 0.01). There was a trend for higher TPO levels in
      patients with severe AA compared with non-severe AA patients. Clinical trials of
      TPO and a related truncated, pegylated molecule, megakaryocyte growth and
      development factor (PEG-rHuMGDF), are awaited to determine whether treatment with
      these drugs will result in increased platelet counts in patients with AA.

PMID- 8982034
TI  - Reversible bone marrow depression by high-dose piperacillin/tazobactam.
AB  - Bone marrow toxicity, mainly neutropenia, has been described as an uncommon
      secondary effect of most beta-lactams, and it is usually related to large
      cumulative doses. Although previously described for piperacillin, no cases of
      marrow depression caused by piperacillin/tazobactam have been reported to date.
      We report a case of reversible pancytopenia, with evidence of bone marrow
      depression, which occurred after a 17 d course of piperacillin/tazobactam. The
      drug was given to an underweight 18-year-old woman, at the usual dosage of 4/0.5
      g three times a day. We stress the need for reducing the recommended dosage when
      treating underweight adult patients, and also of monitoring haematological
      parameters during prolonged treatments.

PMID- 8982035
TI  - Elevated serum interferon gamma and interleukin-6 in patients with necrotizing
      lymphadenitis (Kikuchi's disease).
AB  - We investigated serum levels of interferon alpha, interferon gamma, tumour
      necrosis factor alpha, interleukin-2 (IL-2) and interleukin-6 (IL-6) in patients
      with necrotizing lymphadenitis (Kikuchi's disease) (NL). Four male patients,
      diagnosed as having NL following biopsy of the affected lymph nodes and by the
      clinical course, were included in this study. All four patients had higher than
      normal serum interferon gamma and IL-6 levels during the acute phase, which
      returned to normal levels during the convalescent phase. Interferon alpha, tumour
      necrosis factor alpha and IL-2 were, however, within the normal ranges. Our
      findings indicate the possibility that interferon gamma and IL-6 may play an
      important role in the pathogenesis of NL.

PMID- 8982037
TI  - Pathogenesis of chronic Epstein-Barr virus infection: detection of a virus strain
      with a high rate of lytic replication.
AB  - In rare cases Epstein-Barr virus (EBV) leads to chronic active infection (CAEBV)
      which is characterized by persistant symptoms of infectious mononucleosis.
      Previously we described a case of persisting polyclonal B-cell lymphocytosis
      (PPBL) that was associated with CAEBV. Using reverse transcription and polymerase
      chain reaction we showed that in late passages of a spontaneous cell line, SM,
      latent EB viral genes such as EBNA1, EBNA2, EBNA3A/3B/ 3C, LMP1 and LMP2A were
      active. The master gene of the lytic cycle, BZLF1, was silent. This indicated
      that there was no general defect in immortalization and establishing latency by
      this CAEBV isolate SM. We obtained virus from the standard immortalizing strain
      B95-8 and the CAEBV strain SM from latently infected LCL quantified the number of
      virus particles by competitive PCR and demonstrated that the impaired capacity to
      immortalize umbilical cord blood lymphocytes was a virus strain-specific
      property, and was not due to an incapability to infect purified CD19+ B
      lymphocytes. Transcription of latency- and immortalization-associated genes such
      as EBNA1, EBNA2 and LMP2A was reduced, in contrast to a strongly enhanced
      activity of the master gene of the lytic cycle, BZLF1. A scenario for an
      antagonistic regulation of lytic and latent cycle genes is presented and a role
      for the pathogenesis of CAEBV is discussed.

PMID- 8982036
TI  - Model analysis of the contrasting effects of GM-CSF and G-CSF treatment on
      peripheral blood neutrophils observed in three patients with childhood-onset
      cyclic neutropenia.
AB  - Human cyclic neutropenia (CN) is a rare haematological disorder characterized by
      regular fluctuation in the serial count of blood neutrophils. The oscillations
      occur at subnormal levels with a stable 3-week period. To reduce the risk of
      serious infections during the severe neutropenic nadir phases (< 0.25 x 10(9)
      neutrophils/l) patients are usually treated with recombinant growth factors.
      Compared with G-CSF, which has been shown to enhance the amplitudes
      substantially, the response to GM-CSF is poor: neutrophil numbers are not
      amplified, the cycles remain unchanged or are dampened. However, two cases with a
      modest neutrophil increase have been reported in the literature. In a recently
      published clinical study the different effects of GM-CSF and G-CSF application
      have been investigated in the same patients. Based on a mathematical model of CN
      we previously proposed, the detailed neutrophil data measured in this study are
      analysed by simulation. The contrasting clinical results can be quantitatively
      explained by the model concept of regulatory control together with possible
      individual feedback defects, i.e. abnormally reduced mitotic responsiveness of
      granulopoietic progenitor cells to GM-CSF and G-CSF.

PMID- 8982038
TI  - Neutrophil apoptosis is delayed by the diadenosine polyphosphates, Ap5A and Ap6A:
      synergism with granulocyte-macrophage colony-stimulating factor.
AB  - In addition to ATP, platelets and other cell types can secrete high quantities of
      diadenosine polyphosphates Ap3A, Ap4A, Ap5A and Ap6A. There is increasing
      evidence to show that these molecules can function as novel modulators of cell
      function. For this report we have measured the effects of the diadenosine
      polyphosphates Ap5A and Ap6A on neutrophil apoptosis. These molecules can
      themselves delay neutrophil apoptosis (as assessed by morphology, function. CD16
      expression and chromatin integrity), and are as effective on a molar basis as
      ATP, Ap3A and Ap4A. Moreover, these dinucleotides act synergistically with
      granulocyte-macrophage colony-stimulating factor (GM-CSF) to delay neutrophil
      apoptosis. Thus, diadenosine polyphosphates may act, in concert with cytokines,
      as novel modulators of neutrophil function and survival in certain types of
      inflammatory conditions.

PMID- 8982039
TI  - Diclofenac-induced immune haemolytic anaemia: simultaneous occurrence of red
      blood cell autoantibodies and drug-dependent antibodies.
AB  - During the last 5 years we have identified a total of 17 patients (nine females
      and eight males aged between 53 and 85 years) with immune haemolytic anaemia
      related to diclofenac (a nonsteroidal anti-inflammatory drug). All patients
      developed acute intravascular haemolysis. Two patients died, and eight patients
      developed temporary renal failure that required haemodialysis. The direct
      antiglobulin test was positive with anti-IgG and anti-C3d in all cases, with anti
      IgA in 4/10 cases tested, and negative with anti-IgM. The indirect antiglobulin
      test was moderately or weakly positive in 11 cases, and IgG autoantibodies could
      be eluted from the red blood cells (RBCs) of all patients. Initially, the
      diagnosis of autoimmune haemolytic anaemia of warm type was suggested in all
      cases. All patients had simultaneously developed autoantibodies and drug
      dependent antibodies. The majority of drug-dependent antibodies (n = 13) reacted
      with urine containing the drug and its metabolites (ex vivo antigen), the native
      drug, and diclofenac-treated RBCs. The antibodies in the remaining four cases
      were detectable only in the presence of ex vivo antigen. Diclofenac appears to
      bind only weakly to RBCs in the absence of the drug-dependent antibodies. We
      conclude that diclofenac forms neoantigens with RBCs that may stimulate the
      production of autoantibodies and drug-dependent antibodies. The resulting
      haemolytic syndrome is very similar to autoimmune haemolytic anaemia of warm
      type.

PMID- 8982041
TI  - An improved animal model for studying desferrioxamine.
AB  - A hamster model has been developed for studying desferrioxamine. The hamster
      shows many similarities to man in terms of plasma stability and metabolites
      formed from desferrioxamine. The [59Fe]ferritin derived from rats has been shown
      to be sequestered into liver parenchymal cells when injected intravenously into
      hamsters. The technique has proved sufficiently sensitive to enable detection of
      differences of < 1% of the radioactivity administered in the elimination of iron.
      Alterations in iron excretion were seen when dosing desferrioxamine via different
      routes. The principal route of iron excretion was into the intestines. The
      effectiveness of the dosing routes for desferrioxamine in removing iron were
      subcutaneous (10.5%) > intravenous (6.25%) > oral (3.66%) > control (2.19%). A
      dose-response relationship was demonstrated using the intravenous dose route. The
      model offers a simple method for comparing the efficacy of administration routes
      for determining the optimal use of desferrioxamine.

PMID- 8982040
TI  - N-acetylglucosamine kinase and N-acetylglucosamine 6-phosphate deacetylase in
      normal human erythrocytes and Plasmodium falciparum.
AB  - The major pathways of glucose metabolism in the malaria parasite, Plasmodium
      falciparum, have now been elucidated, and the structures and properties of
      parasite-specific enzymes are presently being investigated. Little is known,
      however, about the enzymes catalysing monosaccharide interconversions in the
      parasite. In the present investigation we have examined the pathway of N
      acetylglucosamine catabolism which, in higher organisms, involves the following
      reaction sequence: N-acetylglucosamine -->N-acetylglucosamine 6-phosphate-
      >glucosamine 6-phosphate-->fructose 6-phosphate. Assay of the specific kinase
      (E.C. 2.7.1.59) catalysing the phosphorylation of the sugar showed that the
      enzyme is present in Plasmodium extracts as well as in normal human erythrocytes;
      specific activities of 7.2 and 5.3 nmol/h/mg protein were measured for the
      parasite and erythrocyte extracts, respectively, N-Acetylglucosamine 6-phosphate
      deacetylase (E.C. 3.5.1.25), catalysing the second reaction, was also detected in
      both normal and Plasmodium-infected erythrocytes. At 75% parasitaemia, the
      deacetylase activity was close to 3 times higher than that of normal control
      cells. The erythrocyte deacetylase was purified approximately 16,000-fold by
      chromatography on DE52 cellulose, chromatofocusing, and size exclusion
      chromatography. Attempts to purify the parasite enzyme by the same procedures
      were unsuccessful due to loss of activity. A partially purified erythrocyte
      deacetylase preparation (eluted from DE52 cellulose) had a pH optimum of 7.5, a
      pI of 6.0, as indicated by chromatofocusing, and a K(m) of 29 microM. In
      conjunction with previous investigations, the present study indicated that all
      three enzymes required for N-acetylglucosamine utilization are present in
      Plasmodium parasites as well as in normal erythrocytes.

PMID- 8982042
TI  - Soluble CD16 (sCD16), a marker of malignancy in individuals with monoclonal
      gammopathy of undetermined significance (MGUS).
AB  - There are no well-defined host markers to determine which patients with a
      diagnosis of monoclonal gammopathy of undetermined significance (MGUS) will
      progress to multiple myeloma (MM). In this preliminary study we measured
      plasmatic soluble Fe gamma receptor type III (sFe gamma RIII or sCD16) in 54
      individuals with MGUS. 35 patients with multiple myeloma (MM) and 29 healthy
      controls. We confirmed, through receiver operating characteristic (ROC) curve
      analysis, that a low level of sCD16 discriminates MM patients from controls.
      Indeed, for a sCD16 value of 1.3 micrograms/ml, the sensitivity, as well as the
      specificity, of this discrimination were both equal to 83%, i.e. 83% of MM
      patients had a plasmatic sCD16 value < 1.3 micrograms/ml compared with only 17%
      of controls. Moreover, ROC curve analysis showed that a low sCD16 level also
      identifies among MGUS patients a subgroup of patients who rapidly progress
      towards multiple myeloma: in this comparison, for a sCD16 level of 1.3
      micrograms/ml. sensitivity and specificity were 70% and 79% respectively.
      Therefore a low sCD16 level in MGUS indicated a high likelihood of rapid
      evolution of MM. In contrast to sCD16, soluble IL-6R did not appear to be
      discriminant in this study.

PMID- 8982043
TI  - Fluorescence in situ hybridization in combination with morphology detects minimal
      residual disease in remission and heralds relapse in acute leukaemia.
AB  - Fluorescence in situ hybridization in combination with morphology (MGG/FISH) was
      used to detect minimal residual disease (MRD) in complete remission (CR) in 12
      cases of acute leukaemia (six MDS-AML, five de novo AML, one pre-B ALL) with
      numerical chromosomal aberrations at diagnosis. Residual leukaemic cells could be
      detected in the remission bone marrows by MGG/FISH in five patients, whereas the
      other seven showed no abnormalities. All five patients with signs of MRD at CR
      relapsed in the bone marrow with 2-9 months, in contrast to two of seven with a
      normal finding by MGG/FISH at CR. In both these patients a second MGG/FISH
      analysis showed that a subpopulation of leukaemic blasts had reappeared, 4 and 5
      months prior to the leukaemia becoming clinically overt. One patient suffered a
      CNS relapse, but without any evidence of bone marrow involvement. The remaining
      four patients with no evidence of MRD at CR were still in haematological
      remission at follow-up after 4, 11, 12 and 13 months, respectively. We conclude
      that MGG/FISH seems to be a clinically useful method to detect MRD in acute
      leukaemia and to predict relapses, particularly when repeat studies are performed
      during CR.

PMID- 8982044
TI  - TEL-AML1 fusion in acute lymphoblastic leukaemia of adults. M.R.C. Adult
      Leukaemia Working Party.
AB  - A number of fusion genes have been identified by study of acquired chromosomal
      translocations. Their detailed characterization has provided insights into
      mechanisms of leukaemogenesis and has enabled the development of molecular
      methods to assist in the diagnosis and monitoring of residual disease after
      treatment. The TEL-AML1 fusion gene is associated with a cryptic
      t(12:21)(p12:q22) translocation, and is the commonest known genetic abnormality
      in childhood B-cell precursor acute lymphoblastic leukaemia (ALL), occurring in
      about 25% of cases. We have used RT-PCR, followed by Southern blotting and direct
      sequencing, to establish the incidence of TEL-AML1 rearrangement in 131 adults
      with acute leukaemia (101 with ALL and 30 with chronic myeloid leukaemia in
      blastic crisis). Three patients were positive for TEL-AML1 transcripts. All three
      had common-ALL. All other patients were negative for TEL-AML1. We conclude that
      the TEL-AML1 fusion gene is found in adult ALL, though less commonly than in
      children.

PMID- 8982045
TI  - Prognostic significance of additional chromosome abnormalities in adult patients
      with Philadelphia chromosome positive acute lymphoblastic leukaemia.
AB  - The clinical and biological significance of additional chromosome aberrations was
      investigated in a large series of 66 adult patients with Philadelphia (Ph)
      chromosome positive acute lymphoblastic leukaemia (ALL). Additional chromosome
      changes were observed in 71% of the cases. 9p abnormalities were identified in
      26%, and monosomy 7 as well as hyperdiploid karyotypes 50 were both found in 17%
      of cases. 9p anomalies were characterized by a low complete remission (CR) rate
      (58%) and an extremely short median remission duration (MRD: 100 d). In patients
      with monosomy 7, the poor treatment outcome was confirmed (CR rate 55%: MRD 113
      d). In contrast, all patients with hyperdiploid karyotypes 50 achieved CR, and
      the overall survival was superior to all other Ph-positive ALL patients except
      those without additional chromosome aberrations. Exclusive rearrangement of the
      minor breakpoint cluster region of the BCR gene and lack of coexpression of
      myeloid-associated antigens in cases with 9p anomalies as well as a high
      frequency of rearrangements of the major breakpoint cluster region of the BCR
      gene in patients with monosomy 7 (89%) further substantiated that additional
      chromosome aberrations may characterize distinct subgroups of Ph-positive ALL.
      Moreover, the necessity of the complementing use of chromosome banding analyses,
      polymerase chain reaction (PCR) assays, and fluorescence in situ hybridizations
      in the accurate identification of Ph-positive patients has become evident due to
      variant Ph translocations in 3%, and negative PCR assays in 4% of the cases.

PMID- 8982046
TI  - Pitfalls in the immunophenotyping of leukaemia and leukaemic lymphomas: survey of
      9 years of quality control in The Netherlands. Dutch Cooperative Study Group on
      Immunophenotyping of Haematological Malignancies (SIHON).
AB  - During the last decade, biannual quality controls were performed in the
      Netherlands focusing on the immunophenotyping of leukaemic haematological
      malignancies. All results on 48 specimens obtained by 18-34 laboratories were
      analysed. The interlaboratory variability and percentages of discordant results
      from 30 markers were measured by assessing false positive or negative (cut-off
      10%) results in comparison with median results of the group. The quality of the
      immunophenotypic diagnoses obtained from the interpretation of these markers in
      relation to clinical data was evaluated by scoring them as 'correct', 'minor
      fault', 'major fault', 'not based upon the markers used', and 'no diagnosis',
      CD3, CD8, CD19, CD61 and Sm lambda had the lowest percentage discordancy (sum of
      total negative and positive discordant values 5-7.5% of assays): CD13, CD15,
      cyCD22, CD33 and TdT scored worst with 14-20% cumulative discordancy. The
      analysis of each diagnosis yielded 78% acceptable immunophenotypic conclusions
      (correct 54% and minor fault 24%). It appeared that the major faults in
      immunophenotyping were caused by suboptimal antibody selection and erroneous
      interpretation of the results obtained, rather than by technical errors. Large
      differences per diagnostic category were observed, with the best scores for
      mature B-cell leukaemias, AMLs and common-ALL, and the poorest scores for T-cell
      malignancies which were correctly diagnosed in only 24-60% of specimens. Mature T
      NHL and T-PLL were mistakenly diagnosed as T-ALL by 40% of the centres.
      Misinterpretation of TdT immunofluorescence or omitting this marker contributed
      significantly to these wrong diagnoses. A median of 4% of immunophenotypic
      diagnoses were not based on a correct panel of antibodies, but upon the
      morphology of the accompanying blood smear, and was often flawed by
      overinterpretation. In conclusion, both the technical performance of
      immunophenotyping of haematological malignancies in The Netherlands and the
      procedure by which a final diagnosis is obtained needs improvement, especially
      for T-cell malignancies.

PMID- 8982047
TI  - Quantitative PCR of the immunoglobulin heavy chain gene using genomic DNA.
AB  - Techniques currently available enable the detection of clonal rearrangements of
      the immunoglobulin heavy chain gene using fluorescent PCR technology. It is
      possible to use this technique to analyse minimal residual disease throughout
      patient treatment: however, without the development of a quantitative assay, only
      the presence or absence of a clonal population can be determined. We describe
      here the development of a quantitative competitive PCR technique using genomic
      DNA which enables the rate of clearance of disease to be measured. In future, the
      ability to detect and also quantitate minimal residual disease may enhance the
      application of molecular investigations in the clinical management of patients.

PMID- 8982048
TI  - Thrombocytosis in patients with acute promyelocytic leukaemia during all-trans
      retinoic acid treatment.
AB  - In 26 acute promyelocytic leukaemia (APL) patients treated with all-trans
      retinoic acid (ATRA), 23% had platelet counts between 459 and 800 x 10(9)/I
      during treatment. These values, observed between days 28 and 45 of ATRA
      treatment, were transient and asymptomatic. We report two APL cases with platelet
      counts > 1000 x 10(9)/I during ATRA therapy who were treated with recombinant
      interferon alpha. In both cases ATRA doses were not modified, no complications
      secondary to thrombocytosis were seen, and they subsequently achieved complete
      remission. It is suggested that IL-6 may play an important role in the
      pathogenesis of the thrombocytosis induced by ATRA. To our knowledge, this is the
      first report of thrombocytosis occurring during ATRA treatment.

PMID- 8982049
TI  - A (15;17) translocation not associated with acute promyelocytic leukaemia.
AB  - We report a woman with acute myeloid leukaemia (AML) type M2 according to FAB
      classification, showing a t(15;17) apparently identical to that of acute
      promyelocytic leukaemia (APL) on conventional cytogenetic analysis. Fluorescence
      in situ hybridization (FISH) using cosmidic probes specific for RAR alpha and
      PML, regions did not show a fusion signal as in APL. The breakpoints were
      assigned to 15q24.3 and 17q21.1. Detailed molecular analyses did not reveal any
      involvement of RAR alpha and PML genes. The patient was resistant to several
      front-line AMI treatments and to all-trans retinoic acid (ATRA). These findings
      reinforce FISH and RT-PCR as useful tools for the characterization of a t(15;17)
      as the translocation specifically associated with APL.

PMID- 8982050
TI  - Clonal involvement of eosinophils in therapy-related myelodysplastic syndrome
      with eosinophilia, translocation t(1;7) and lung cancer.
AB  - We report a therapy-related MDS (RAEB) patient with eosinophilia, unbalanced
      translocation der(7)t(1;7) (q12;q22) and lung cancer. We observed no increase in
      cytokine levels in serum or in the conditioned medium (CM) of peripheral T cells
      cultured with or without IL-2. When bone marrow (BM) cells were cultured with GM
      CSF, IL-3 and SCF in a semisolid system, the colonies were exclusively
      eosinophilic. Cytogenetic analysis of the colony cells identified the same
      chromosome abnormality in all metaphases to that of BM cells. Suspension and
      clonogenic colony assay of BM cells cultured with various cytokines showed
      predominant eosinophilic growth and differentiation with GM-CSF, but not with the
      other cytokines examined. These findings, together with mild morphological
      abnormalities of eosinophils, indicate clonal involvement of eosinophils in the
      myelodysplastic syndrome (MDS) clone, and that the eosinophilia was derived from
      the neoplastic clone with the translocation and was not associated with the
      patient's lung cancer.

PMID- 8982051
TI  - Transplantation of peripheral blood progenitor cells from HLA-identical sibling
      donors. European Group for Blood and Marrow Transplantation (EBMT).
AB  - Transplantation of peripheral blood progenitor cells (PBPCs) has largely replaced
      autologous bone marrow transplantation. The same might occur in the allogeneic
      setting if the favourable initial experience with allogeneic PBPCT is confirmed.
      We analysed all primary transplants utilizing unmodified PBPC from HLA-identical
      sibling donors reported to the European Group for Blood and Marrow
      Transplantation (EBMT) for 1994. 59 patients with a median age of 39 years
      received myeloablative therapy for acute myelogenous leukaemia (23 patients,
      acute lymphoblastic leukaemia (13), chronic myelogenous leukaemia (nine),
      lymphoma (seven), or other diagnoses (seven) mostly of advanced stages followed
      by transplantation of allogeneic PBPC. Three patients died soon after grafting,
      the others showed prompt haemopoietic recovery with median times to recover an
      absolute neutrophil count (ANC) above 0.5 and 1.0 x 10(9)/I of 15 (range 9-27)
      and 17d (range 10-28) respectively. Time to platelet recovery above 20 or 50 x
      10(9)/I was 16 (range 9-76) and 18d (range 12-100) respectively. 27 patients
      (46%) developed no or mild acute graft-versus-host disease (GVIID). The incidence
      of moderate (grade II) disease was 27%; 24% of the patients developed severe
      acute GVHD (grades III or IV), 55% of patients who were alive 90d after
      transplantation developed chronic GVHD, the probability to develop extensive
      chronic GVHD was 32% (95% confidence interval 22-42) with a median follow-up of
      14 months. Overall and event-free survival (EFS) at 1 year were 54% (CI 48-60)
      and 50% (CI 43-57), respectively, the relapse incidence was 23% (CI 17-29). EFS
      was 67% (CI 55-79) in patients transplanted for acute leukaemias in first
      complete remission, chronic myelogenous leukaemia in first chronic phase, or
      severe aplastic anaemia. Transplantation of allogeneic PBPC resulted in prompt
      and durable engraftment. The incidence and severity of acute and chronic GVHD
      seemed comparable to that observed after allogeneic BMT. Overall and event-free
      survival in this cohort of patients, most of whom suffered from advanced
      leukaemia or lymphoma, is encouraging, suggesting that the high numbers of T
      lymphocytes and/or natural killer cells contained in a typical PBPC collection
      product exert a vigorous graft-versus-leukaemia effect. Further evaluation of
      allogeneic PBPCT is highly desirable.

PMID- 8982052
TI  - A diagnostic test for heparin-induced thrombocytopenia: detection of platelet
      microparticles using flow cytometry.
AB  - Based on our previous observation that heparin-induced thrombocytopenia (HIT)
      sera can generate platelet microparticles from washed platelets in a heparin
      dependent fashion, we developed a test for HIT using flow-cytometry to measure
      heparin-dependent platelet microparticle formation. During the developmental
      phase of the assay the optimal physical conditions for microparticle generation
      were defined. 133 sera were then evaluated using the microparticle assay and the
      serotonin release assay to determine the threshold for defining a positive result
      that gave optimal sensitivity and specificity. The microparticle assay was then
      prospectively evaluated against the serotonin release assay in 202 sera referred
      to our laboratory for HIT testing. Overall agreement between the two assays was
      96% (Cohen's kappa = 0.91). When the clinical data were reviewed on patients
      whose sera gave discrepant results between the two assays, no case of HIT was
      detected by one assay and missed by the other. The platelet microparticle assay
      is as accurate as the serotonin release assay and may be a useful non-radioactive
      test for HIT.

PMID- 8982053
TI  - Oligoclonal accumulation of T cells in peripheral blood from patients with
      idiopathic thrombocytopenic purpura.
AB  - To determine whether clonal T cells accumulate in idiopathic thrombocytopenic
      purpura (ITP), we performed single-strand conformation polymorphism (SSCP)
      analysis to detect T-cell receptor (TCR) beta-chain usage of peripheral T cells.
      We detected significantly more oligoclonal T cells (15.5 +/- 8.9 bands
      representative for clonal T-cell expansions) in peripheral blood from ITP
      patients than from healthy donors (2.8 +/- 2.6 bands). Frequently used V beta
      genes in these accumulated T cells in ITP were V beta 3, 6, 10, 13.1 and 14. To
      determine whether these bands were derived from clonal T cells, presumably in a
      preactivated state, we established some T-cell clones (expressing CD4 and TCR V
      beta 6. 13.1. or 14) by nonspecific stimulation from patients peripheral
      mononuclear cells, and examined their clonotypes. Clonal identities for three out
      of seven clones tested were confirmed using SSCP analyses to compare the
      migration of their beta-chain complementarity determining region 3 (CDR3) cDNAs,
      expanded by polymerase chain reaction (PCR) with those from peripheral blood.
      Therefore, distinctive T-cell clones accumulated in the periphery in ITP and they
      may be related to the autoimmune-mediated destruction of platelets.

PMID- 8982054
TI  - Probable regulation of factor VIIa-tissue factor and prothrombinase by factor Xa
      TFPI and TFPI in vivo.
AB  - Given that factor VIIa-tissue factor (TF) probably initiates coagulation in vivo,
      this study investigated the relationship between plasma concentrations of factor
      VIIa and prothrombin fragment 1 + 2 in plasma (the latter as an index of
      prothrombinase activity in vivo). The relationships between these two parameters
      and the concentrations of tissue factor pathway inhibitor (TFPI) and factor Xa
      TFPI in plasma were also investigated. TFPI inactivates factor Xa in a reaction
      accelerated by heparin, whereas factor Xa-TFPI inactivates factor VIIa-TF and
      prothrombinase. Established enzyme-linked immunosorbent assays (ELISAs) were used
      to quantify TFPI and prothrombin fragment 1 + 2, whereas we developed an ELISA to
      quantify factor Xa-TFPI using affinity purified rabbit (anti-human TFPI)-IgG and
      chicken anti-(human factor Xa-TFPI)-IgY as the capture and detector antibodies,
      respectively. Plasma factor VIIa was quantified using truncated tissue factor.
      The concentrations of factor VIIa and prothrombin fragment 1 + 2 increased in
      parallel in the plasmas of up to 145 healthy adults assayed (P = 0.007), as did
      the concentrations of factor VIIa and TFPI (P = 0.0039), and prothrombin fragment
      1 + 2 and TFPI (P = 0.013). In contrast, there was an inverse relationship
      between the concentrations of free factor Xa-TFPI and factor VIIa (P < 0.0001)
      and free factor Xa-TFPI and prothrombin fragment 1 + 2 (P = 0.0095). These
      results are consistent with factor Xa-TFPI regulating factor VIIa-tissue factor
      and prothrombinase in vivo.

PMID- 8982055
TI  - A non-thrombocytopenic bleeding disorder due to an IgG4-kappa anti-GPIIb/IIIa
      autoantibody.
AB  - Autoantibodies in chronic immune thrombocytopenic purpura occasionally interfere
      with platelet function. We describe a patient with a normal platelet count who
      had clinically significant mucosal bleeding, a prolonged bleeding time and
      abnormal platelet aggregation. The patient had high titres of an IgG4 kappa
      autoantibody, directed to a cation-dependent epitope on platelet glycoprotein
      IIb/IIIa, which blocked the binding of fibrinogen and fibronectin to this
      complex. Corticosteroid treatment resulted in clinical improvement and a marked
      drop in autoantibody concentration. The lack of thrombocytopenia in this patient,
      despite high autoantibody levels, is best explained by the poor recognition of
      IgG4 antibodies by phagocytic cells.

PMID- 8982056
TI  - Low response to high-dose intravenous immunoglobulin in the treatment of acquired
      factor VIII inhibitor.
AB  - Prednisone is the classic first-line therapy to suppress an acquired factor VIII
      inhibitor and may achieve complete remission in about 30% of patients. More
      recently, promising results have been reported with high-dose intravenous
      immunoglobulin (IVIg). However, after an extensive review of the literature, we
      found only three complete remissions (12%) among the 26 assessable patients
      treated by IVIg. These data are in agreement with the low response to IVIg that
      we experienced in our series of patients. This study suggests that steroids
      should still be preferred to IVIg, an expansive therapy, to suppress an acquired
      factor VIII inhibitor.

PMID- 8982057
TI  - Bone marrow assessment in B-cell chronic lymphocytic leukaemia: aspirate or
      biopsy?

PMID- 8982058
TI  - Cytokines and platelet activation in stored pooled buffy-coat-derived platelet
      concentrates: the issue of transfusional reactions.

PMID- 8982059
TI  - Obesity: evaluation and treatment.
AB  - Obesity as a chronic condition among large numbers of people is a disease of
      recent origin, often but by no means always associated with dietary habits and
      sedentary lifestyle. Many obese people want to lose weight, and may have tried to
      do so numerous times with self-help or proprietary weight-loss programs. When
      they seek a physician for help in losing weight-or when a physician advises an
      obese patient to lose weight as part of a clinical strategy-care must be taken to
      "match" the patient to an appropriate therapeutic program with appropriate
      therapeutic goals. History and physical examination and psychologic evaluation
      are essential elements of patient screening. Complications of obesity must be
      taken into account in any treatment plan. The multidisciplinary management
      strategy is most likely to succeed in helping the patient lose weight. It also
      avoids untoward events associated with complications or concomitant disease. The
      multidisciplinary approach is especially important when the patient does not lose
      weight, and alternative strategies must be considered, such as surgical
      approaches.

PMID- 8982060
TI  - Sequence and functional analysis of an upstream regulatory region of human HOXA7
      gene.
AB  - The Hox genes have been known to be involved in pattern formation during
      vertebrate development through differential expression along the anteroposterior
      body axis. Human homologue of position-specific regulatory region of murine Hoxa
      7 was cloned from human genomic library. The restriction map of the 18-kb insert
      was determined, of which a 3.9-kb region was sequenced. Homology plot between the
      murine and the corresponding human sequence showed high sequence conservation
      over 70% in several regions. The homologous region has been reduced to about 1.1
      kb (HCR: human control region), which contained several putative factor binding
      sites. The function of HCR was analyzed in transgenic mice and turned out to be a
      position-specific regulatory element of human, setting the precise anterior
      boundary of expression in transgenic embryos; at day 12.5 post-coitum a distinct
      anterior limit of expression was noted at the level of C5 in neural tube and
      spinal ganglia in transgenic embryos. These results indicate that the regulatory
      sequences as well as the molecular mechanism for Hox gene expression are highly
      conserved among vertebrates.

PMID- 8982061
TI  - Cloning and functional analysis of a beta-tubulin gene from a benomyl resistant
      mutant of Aspergillus parasiticus.
AB  - A genomic DNA library prepared from a benomyl resistant strain of Aspergillus
      parasiticus was screened with a Neurospora crassa beta-tubulin gene probe. A
      unique A. parasiticus genomic DNA fragment, thought to carry a mutant beta
      tubulin gene (benr), was isolated. Two plasmids, pYT1 and pYTPYRG, carrying the
      putative benr gene or benr plus a second selectable marker (pyrG), respectively,
      were used to transform a benomyl sensitive strain of A. parasiticus (CS10) to
      determine if benr conferred benomyl resistance (BenR). BenR colonies were
      obtained with pYTPYRG, pYT1 or pYT1 cotransformed with pPG3J which carries a
      functional pyrG gene. No BenR colonies were obtained without added DNA or with
      pPG3J only (controls). Southern hybridization analysis of BenR and BenS
      transformants suggested that plasmid integration occurred most frequently at the
      chromosomal bens locus, however evidence for gene conversion and heterologous
      recombination was also observed. The predicted amino acid sequence of benr
      displayed a high degree of identity (> 93%) with other fungal beta-tubulin genes
      which confer benomyl resistance. Sequence analysis together with the genetic data
      suggested that benr encodes a functional mutant beta-tubulin.

PMID- 8982062
TI  - Generality of a functional initiator consensus sequence.
AB  - Transcriptional initiator (Inr) elements, like TATA boxes, are found in the core
      promoters of many eukaryotic protein-coding genes. To facilitate the dissection
      of transcription initiation mechanisms, and to identify Inr elements within known
      and newly-discovered genes, the precise DNA sequence requirements for Inr
      activity must be defined. Previously, we reported a preliminary Inr consensus
      sequence based on an extensive mutant analysis carried out in HeLa cell extracts.
      This analysis was limited, however, because it was performed only with an in
      vitro transcription assay and with the mutants in only one promoter context. In
      this study, we have assessed the general validity of the functional Inr consensus
      sequence by analyzing a selected set of mutants in additional promoter contexts
      and with both in vivo and in vitro assays. In addition, we analyzed the
      evolutionary conservation of the Inr consensus sequence by determining the
      sequence requirements for Inr function in Drosophila embryo extracts. The results
      demonstrate the generality and strict conservation among vertebrates and
      invertebrates of the Inr consensus sequence, Py Py A+1 N T/A Py Py.

PMID- 8982063
TI  - Cloning and sequencing of a gene coding for a novel dextransucrase from
      Leuconostoc mesenteroides NRRL B-1299 synthesizing only alpha (1-6) and alpha (1
      3) linkages.
AB  - The coding region for a Leuconostoc mesenteroides NRRL B-1299 dextransucrase gene
      (dsrA) was isolated and sequenced. Using a pair of primers designed on the basis
      of two highly conserved amino-acid (aa) sequences in L. mesenteroides NRRL B-512F
      dextransucrase and streptococcal glucosyltransferases (GTFs), a fragment of dsrA
      was amplified by the polymerase chain reaction (PCR). This PCR product was used
      as an hybridization probe to isolate a 1.8-kb fragment identified as the central
      region of dsrA. Cleavage by Sac I of this fragment allowed two probes to be
      obtained to isolate the 5' and the 3' ends of dsrA. The nucleotide sequence of
      the dsrA gene was determined and found to consist of an open reading frame (ORF)
      of 4870 base pairs (bp) coding for a 1290-aa protein with an M(r) of 145590. The
      aa sequence exhibited a high similarity with other GTFs. The two domains
      previously described in GTFs are conserved in DSRA: an N-terminal conserved
      domain and a C-terminal domain composed of a series of repeats. Surprisingly, the
      expected signal peptide was not detected. The entire gene was reconstructed and
      the activity of DSRA was investigated. The dextran produced appeared to be
      composed of 85% alpha (1-6) and 15% alpha (1-3) linkages and the oligosaccharides
      synthesized in the presence of maltose were mainly composed of alpha (1-6)
      linkages. This enzyme is a novel dextransucrase from L. mesenteroides NRRL B-1299
      producing no alpha (1-2) linkages and is the first glucosyltransferase having no
      signal peptide described.

PMID- 8982064
TI  - Integrative vectors for constructing single-copy transcriptional fusions between
      Bacillus subtilis promoters and various reporter genes encoding heat-stable
      enzymes.
AB  - Here, we report on the construction of three integrative plasmids for Bacillus
      subtilis (Bs) allowing in vitro construction of transcriptional fusions. These
      plasmids contain a neomycin- or tetracycline-resistance cassette and one of three
      promoterless genes: bgaB (encoding beta-galactosidase), cat (chloramphenicol
      acetyltransferase), or xylE (catechol 2,3-dioxygenase). All cassettes are flanked
      by the 3'- and 5'-ends of the amyE gene (encoding alpha-amylase) allowing
      integration of these cassettes at the amyE locus of the Bs chromosome. For
      propagation and selection in Escherichia coli, the plasmids contain the pBR322
      origin of DNA replication and the beta-lactamase-encoding bla gene. Four unique
      restriction sites can be used for insertion of restriction fragments carrying
      promoter fragments. All three reporter genes express heat-stable enzymes (stable
      up to at least 50 degrees C for 30 min) as shown here. We would like to point to
      the modular nature of these plasmids where the three reporter genes and the two
      resistance cassettes can be combined in any permutation. The versatility of the
      promoter-probe vectors was demonstrated by the integration of the promoters of
      the dnaK and groE operons of Bs and following their heat-inducible expression.

PMID- 8982066
TI  - Molecular cloning of a cDNA encoding 3-ketoacyl-acyl carrier protein synthase III
      from leek.
AB  - 3-Ketoacyl-acyl carrier protein synthase III (KAS III) catalyzes the initial
      condensation of malonyl-acyl carrier protein (ACP) with acetyl-CoA in plant and
      bacterial fatty acid biosynthesis. The first cDNA clone encoding KAS III from a
      monocot is reported here. A cDNA clone was isolated from a leek epidermal cDNA
      library by screening with spinach and Arabidopsis heterologous probes from KAS
      III cDNA clones. When expressed in Escherichia coli, the cloned enzyme was able
      to catalyze the expected condensation reaction, was insensitive to cerulenin (100
      microM) and cross-reacted with spinach KAS III antibody. The 1476-bp cDNA clone
      contained a 1206-bp open reading frame which encoded a 402-amino acid
      polypeptide. The deduced amino acid sequence showed significant similarities to
      other KAS IIIs although the leek sequence had some notable differences in regions
      otherwise completely conserved in dicots. Northern blot analyses indicated that
      KAS III transcript levels were similar in leaf epidermis and parenchyma, although
      developmental changes in transcript levels differed between these two tissues. In
      addition, leek KAS III was expressed in a manner comparable to leek oleoyl-ACP
      thioesterase (OTE), another enzyme of fatty acid biosynthesis, in both tissues.

PMID- 8982065
TI  - Structure and organisation of the pyrimidine biosynthesis pathway genes in
      Lactobacillus plantarum: a PCR strategy for sequencing without cloning.
AB  - This report describes the sequence and structural organisation of the pyrimidine
      biosynthesis pathway genes of Lactobacillus plantarum CCM 1904. It also describes
      an in vitro technique based on PCR for sequencing without cloning. This new
      technique was developed because it was impossible to clone certain parts of the
      L. plantarum genomic DNA in the Escherichia coli host. L. plantarum pyr genes are
      organised as a 9.8-kb operon with the following order: pyrR, pyrB, pyrC, pyrAA,
      pyrAB, pyrD, pyrF and pyrE. There are two major differences from the pyrimidine
      operons of Bacillus subtilis (Quinn et al., J. Bacteriol. 266 (1991) 9113-9127;
      Turner et al., J. Bacteriol, 176 (1994) 3708-3722) and Bacillus caldolyticus
      (Ghim et al., Microbiology 140 (1994) 479-491): the absence of pyrP encoding for
      uracil permease, and the absence of an open reading frame named orf2, whose
      function is unknown. Two mutually exclusive stem-loop structures were predicted
      at the 5'-end of L. plantarum pyr mRNA; this operon could be regulated by
      transcriptional attenuation under the control of PyrR. Complementation of E. coli
      pyrD, pyrF and pyrE mutants was obtained with a L. plantarum genomic DNA library.
      Alignment of the L. plantarum Pyr proteins with other known procaryotic Pyr
      proteins indicates that they display highly conserved regions in Gram-positive
      and Gram-negative bacteria.

PMID- 8982067
TI  - Cloning and expression pattern of Hor v 9, the group 9 pollen isoallergen from
      barley.
AB  - In this study we report the cloning, sequence, and characterization of Hor v 9
      allergen cDNAs from barley (Hordeum vulgare) pollen. Structural homologues of
      Kentucky bluegrass (Poa pratensis) group 9 pollen allergens were identified in a
      cDNA library of barley pollen expressed mRNAs. The Hor v 9 cDNA clone (hvp9742)
      contained an open reading frame encoding 313 amino acids which included a
      putative 27-residue signal peptide and one asparagine sequon for glycosylation.
      The mRNA corresponding to clone hvp9742 was produced abundantly in pollen during
      the late stages of anther development. The protein encoded by clone hvp974 was
      synthesized as a fusion protein in the E. coli expression vector pMAL.
      Immunoblots using antibodies to this recombinant allergen, rHor v 9, showed that
      Hor v 9 protein accumulated during pollen development and was produced maximally
      at pollen maturity. Using these antibodies, we also provide evidence that Hor v 9
      protein localized to the extracellular matrix of mature pollen. Southern blots
      suggested that Hor v 9 allergens exist as multiple isoforms in barley. Sequence
      comparisons showed that the Hor v 9 cDNA clones were also homologous to group 5
      allergens of Timothy grass (Phleum pratense) pollen and canary grass (Phalaris
      aquatica) pollen, and the group 9 allergen of ryegrass (Lolium perenne) pollen.

PMID- 8982068
TI  - Molecular analysis of the Pseudomonas aeruginosa genes, ruvA, ruvB and ruvC,
      involved in processing of homologous recombination intermediates.
AB  - In Escherichia coli, the products of the ruvA, ruvB and ruvC genes are all
      involved in the processing of recombination intermediates (Holliday structures)
      into recombinant molecules. We cloned a 9.4-kb DNA fragment from Pscudomonas
      aeruginosa PAO1 in a plasmid by functional complementation of the UV sensitivity
      of an E. coli strain with ruvABC deleted. In P. aeruginosa, the ruv region seemed
      to form a non-SOS regulated single operon consisting of orf26-ruvC-ruvA-ruvB,
      while in this region of E. coli, ruvA and ruvB form an SOS-regulated operon,
      orf26 and ruvC form a non-SOS operon, and these two operons are split by orf23.
      The deduced amino acid sequences of P. aeruginosa RuvA, RuvB and RuvC proteins
      were 55, 72 and 55% identical to those of the corresponding E. coli Ruv proteins.
      The individual ruv genes of P. aeruginosa complemented the corresponding single
      ruv mutations of E. coli, suggesting that the P. aeruginosa Ruv proteins can
      interact functionally with their E. coli Ruv partners in forming heterologous
      complexes. The sequence alignments of the Ruv proteins were extended by
      incorporation of data about the putative ruv genes obtained from data banks, and
      the RuvB sequences were conspicuously more conserved than the RuvA and RuvC
      sequences.

PMID- 8982069
TI  - Molecular cloning and characterisation of the mouse preprogalanin gene.
AB  - Using a probe obtained by PCR amplification from mouse genomic DNA, a genomic
      clone was isolated covering the entire mouse preprogalanin gene. The mouse gene
      has an exon:intron organisation very similar to that of the rat and human genes.
      The first exon is noncoding while exons 2-5 carry the coding region. Exon 6 also
      encodes the stop codon and a polyadenylation signal. The deduced amino-acid
      sequence of mouse preprogalanin is 94% and 68% identical to the rat and human
      peptide, respectively. The amino-acid sequence of mouse galanin was confirmed by
      RT-PCR amplification of mouse brain RNA. The cloning of the mouse galanin gene
      should allow elucidation of the regulatory characteristics of its promoter and
      facilitate transgenic approaches to the analysis of galanin gene function in this
      species.

PMID- 8982070
TI  - Reexamining interaction of the SH2 domains of SYP and GAP with insulin and IGF-1
      receptors in the two-hybrid system.
AB  - Direct interaction of effector proteins such as the p85 regulatory subunit of
      phosphatidylinositol 3-kinase (PI 3-kinase), SYP (SH2-domain-containing tyrosine
      phosphatase) and GAP (Ras-GTPase activating protein) with the insulin receptor
      (IR) and insulin-like growth factor-1 (IGF-1) type 1 receptor (IGF-1R) has been
      reported in some studies. Interaction of SYP and GAP with IR and IGF-1R was re
      investigated here in the two-hybrid system by assessing his3/lacZ activation in
      S. cerevisiae. The experiments were performed with the cytoplasmic beta domain of
      IR and IGF-1R and various SH2-subdomains of SYP and GAP. None of the subdomains
      of SYP and GAP tested were able to activate his3/lacZ, whereas these reporter
      genes were strongly activated when p85 was used as we have recently shown. Thus,
      interaction of SYP and GAP with IR and IGF-1R, if any, would be weak and/or
      transient as compared to that of p85.

PMID- 8982071
TI  - Characterization of the DNA-binding domain of beta protein, a component of phage
      lambda red-pathway, by UV catalyzed cross-linking.
AB  - beta protein, a key component of Red-pathway of phage lambda is necessary for its
      growth and general genetic recombination in recombination-deficient mutants of
      Escherichia coli. To facilitate studies on structure-function relationships, we
      overexpressed beta protein and purified it to homogeneity. A chemical cross
      linking reagent, glutaraldehyde, was used to stabilize the physical association
      of beta protein in solution. A 67-kDa band, corresponding to homodimer, was
      identified after separation by SDS-polyacrylamide gel electrophoresis.
      Stoichiometric measurements indicated a site-size of 1 monomer of beta protein/5
      nucleotide residues. Electrophoretic gel mobility shift assays suggested that
      beta protein formed stable nucleoprotein complexes with 36-mer, but not with 27-
      or 17-mer DNA. Interestingly, the interaction of beta protein with DNA and the
      stability of nucleoprotein complexes was dependent on the presence of MgCl2, and
      the binding was abolished by 250 mM NaCl. The Kd of beta protein binding to 36
      mer DNA was on the order of 1.8 x 10(-6) M. Photochemical cross-linking of native
      beta protein or its fragments, generated by chymotrypsin, to 36-mer DNA was
      performed to identify its DNA-binding domain. Characterization of the cross
      linked peptide disclosed that amino acids required for DNA-binding specificity
      resided within a 20-kDa peptide at the N-terminal end. These findings provide a
      basis for further understanding of the structure and function of beta protein.

PMID- 8982072
TI  - Analysis of yeast trimethylguanosine-capped RNAs by midwestern blotting.
AB  - Immuno-detection by 'Midwestern' blotting provides a simple way to identify
      trimethylguanosine (TMG) capped RNAs. With this technique, over 20 bands are
      observed when total cellular RNA from Saccharomyces cerevisiae is transferred to
      a nylon membrane and probed with anti-TMG antibodies. Most, if not all, species
      known to contain a TMG cap are detected by this method. Only TMG-capped RNAs are
      detected on Midwestern blots unlike anti-TMG immunoprecipitates. Midwestern
      blotting is a useful alternative to immunoprecipitation and Northern analysis and
      may prove to be a better method for determining the relative abundance of capped
      RNAs. The blots can be reprobed multiple times with labeled antisense
      oligonucleotides to determine the identity of any TMG-capped species for which
      the primary sequence or a clone is available. This dual detection capability
      provides a powerful tool for the analysis of TMG-capped snRNAs and snoRNAs.

PMID- 8982073
TI  - Cloning and sequence analysis of the candidate nicotinic acetylcholine receptor
      alpha subunit gene tar-1 from Trichostrongylus colubriformis.
AB  - A T. colubriformis genomic library in lambda EMBL3 was screened for sequences
      homologous to the Caenorhabditis elegans unc-38 nicotinic acetylcholine receptor
      (nAChR) alpha-subunit gene. The candidate gene tar-1 (for Trichostrongylus
      acetylcholine receptor subunit gene 1) comprising 13704 base pairs was thus
      identified. BLAST comparison of the sequenced clone with GenBank, followed by
      comparison of translated regions in six reading frames with protein databases,
      identified clearly defined tracts corresponding to 12 putative exons sharing high
      sequence homology to other nAChR genes and able to code for sequential regions of
      a putative nAChR alpha-subunit protein (tar-1). Tar-1 shares sequence
      similarities with over 40 nAChR subunit proteins. The highest similarity (91.6%)
      is with unc-38, suggesting that nAChR sequences from nematodes are closely
      related. The sequence includes motifs typical of these molecules including
      adjacent cysteine residues at the ACh binding site and four transmembrane
      regions. The DNA sequence presents the longest genomic tract described for this
      organism and should prove useful as a probe source in the search for nAChR genes
      from this and other nematodes and for studying the molecular mechanism of
      resistance to levamisole, a drug which is known to act on nAChRs of worms and
      which is widely used for parasite control.

PMID- 8982074
TI  - A tightly regulated high level expression vector that utilizes a thermosensitive
      lac repressor: production of the human T cell receptor V beta 5.3 in Escherichia
      coli.
AB  - A series of vectors has been constructed to express the human T cell receptor V
      beta 5.3 under the control of the hybrid trc promoter in Escherichia coli.
      Transcriptional induction of the trc promoter was achieved chemically by using
      isopropyl beta-D-thiogalactopyranoside (IPTG) in a bacterial strain that harbors
      the lacIq gene, or thermally by using the mutant lacIts gene that encodes a
      temperature-sensitive lac repressor [Bukrinsky et al. (1988) Multicopy expression
      vector based on temperature-regulated lac repressor: expression of human
      immunodeficiency virus env gene in Escherichia coli. Gene 70, 415-417]. Several
      of the plasmids tested also contain the E. coli heat-stable enterotoxin II (STII)
      signal sequence for protein secretion. In addition, the gene 10 leader sequence
      from bacteriophage T7 and a minicistron localized upstream of the V beta 5.3
      coding sequence were tested for their potential effect on protein production.
      These elements increased protein yield two-fold when transcription was induced by
      IPTG, but had no detectable effect on protein yield when transcription was
      induced thermally. The highest protein yield was obtained when V beta 5.3 was
      expressed either from plasmid pKB containing the STII signal in strain LJ24, or
      from plasmid pKBi that lacks the signal sequence, in the protease deficient
      strain SG21173 (lon, htpR. clp). Both plasmids contain the lacIts gene, the trc
      promoter, the two transcription terminators of the rrnB operon, and a
      tetracycline selection marker. Production of V beta 5.3 using pKBi-V beta 5.3 in
      strain SG21173 in a 5-liter fermenter under controlled growth conditions yielded
      over 25 mg V beta 5.3/liter culture. Conversion of the lacIts to the lacIqts gene
      yielded vector pKBiq-V beta 5.3 which exhibits complete repression of the trc
      promoter at 30 degrees C. This stringent regulation of the thermally inducible
      trc promoter, the elimination of IPTG, the inclusion of the tetracycline
      resistance gene, and the high level of protein yield should render this
      expression system broadly useful for the high level production of heterologous
      proteins in E. coli, for both basic research and human therapeutic applications.

PMID- 8982075
TI  - Elevated levels of cyclin D1 mRNA in the undifferentiated chick retina.
AB  - The retina is derived from precursor neuroectodermal cells that differentiate
      into six classes of neuronal cells and one class of glial cells (Muller). To gain
      insight into the molecular events underlying retinal differentiation, we used the
      differential display polymerase chain reaction (DD-PCR) technique to identify
      transcripts preferentially expressed in precursor retinal cells prior to their
      differentiation. One of the cDNAs that we selected using this technique encoded
      cyclin D1, a G1 cyclin shown to bind to the retinoblastoma protein (pRB) and
      which is involved in the phosphorylation of pRB during mid to late G1. Similar to
      what has been reported recently in the mouse retina, we found cyclin D1 mRNA to
      be highly expressed in the undifferentiated chick retina. Tissue maturation was
      accompanied by a substantial reduction in cyclin D1 mRNA levels. A similar
      temporal pattern of expression was observed in the developing brain although
      transcript levels were lower than in the retina. In contrast, cyclin D1 mRNA
      levels increased with differentiation in the kidney. These results suggest that
      the proliferating cells of the developing chick retina require exceptionally high
      levels of cyclin D1 mRNA, perhaps to promote progression through the cell cycle
      by countering the effect of molecules with a negative role in the cell cycle such
      as pRB.

PMID- 8982076
TI  - Sequence and analysis of the replication region of the Staphylococcus xylosus
      plasmid pSX267.
AB  - The region of the 29.5-kb plasmid pSX267 from Staphylococcus xylosus DSM 20267
      that is required for autonomous replication in staphylococci was isolated on a
      1.8-kb DNA fragment. The sequence analysis of the fragment yielded two open
      reading frames, repA and orf2, encoding proteins of 37.2 and 13.2 kDa,
      respectively. The deduced amino acid sequence of repA showed similarity to the
      replication initiator protein of plasmid pAD1 from Enterococcus faecalis, to two
      proteins of unknown function encoded by the E. faecalis plasmid pCF10 and the
      lactobacillus helveticus plasmid pLJ1, and surprisingly to the mouse interferon
      response element binding factor 1. The repA gene of pSX267 is indispensable for
      replication suggesting that it encodes the replication initiator protein of
      pSX267. Introduction of a frameshift mutation into repA or deletion of 26 codons
      at its 3'-end resulted in nonreplicative plasmids. Removal of sequences required
      for repA expression also abolished replication. Complementation experiments with
      repA in trans identified the ori of pSX267 within the repA coding region. The
      second orf, which is located downstream of repA, could be deleted without
      affecting plasmid replication. It seems to be a nonfunctional remainder of a
      rolling circle plasmid of the pC194/pUB110 family, since its deduced amino acid
      sequence resembles the pC194/pUB110-type replication proteins. The minimal
      replicon of pSX267 defined so far comprises 1255 bp. Besides repA, no other
      plasmid-encoded gene is required to mediate replication in staphylococci.

PMID- 8982077
TI  - Interference of Myb transactivation activity by a conditional dominant negative
      protein: functional interference in a cytotoxic T-cell line results in G1 arrest.
AB  - The ability to ablate the activity of specific transcription factors in vivo is a
      potentially important tool to study their roles in cellular processes such as the
      cell cycle. Previously, production of a dominant interfering c-Myb protein
      (comprising a fusion of the c-Myb DNA binding domain with the Drosophila
      Engrailed transrepressor) was found to inhibit the proliferation of immature
      thymocytes in the developing thymus of transgenic mice. We report here the
      further development of this stratagem by rendering the c-Myb/Engrailed protein
      conditionally active by fusion to a modified estrogen receptor hormone binding
      domain, ER. Co-transfection experiments in NIH 3T3 fibroblasts showed that the
      resulting chimeric protein, Myb/En/ER, repressed transactivation of a c-Myb
      responsive reporter only in the presence of the synthetic steroid, 4
      hydroxytamoxifen (OHT). Additionally, we found that Myb/En/ER could counteract
      transactivation by C/EBP-beta of the mim-1 promoter, which contains juxtaposed
      Myb and C/EBP binding sites. Cytotoxic T-cells stably producing the inactive
      Myb/En/ER protein were readily obtained by gene transfection. The addition of OHT
      to these cells resulted in inhibition of proliferation and arrest in G1. The
      utility of this experimental system to study Myb and other transcription factors
      is discussed.

PMID- 8982078
TI  - Cloning and sequence analysis of the Rhizobium etli ccmA and ccmB genes involved
      in c-type cytochrome biogenesis.
AB  - In this paper we describe the sequence analysis of two Rhizobium etli genes (ccmA
      and ccmB) which are believed to participate in the transport of the haem moiety
      to the periplasm in other bacterial species. The characterized DNA region was
      isolated by complementation of a R. etli Tn5mob induced mutant (CFN4201) which
      was affected in the production of c-type cytochromes. Sequence analysis of this
      region identified three open reading frames, two were identified as the ccmA and
      ccmB genes. The predicted protein sequence of ccmA showed significant homology
      with ATP binding proteins of the ABC-type transporter systems, while ccmB encodes
      for a hydrophobic protein probably associated with the ccmA gene product. The
      Tn5mob insertion in CFN4201 strain was located in the carboxy terminus of CcmB.
      Restriction mapping of the EcoRI fragment containing the Tn5mob insertion showed
      that it involved a deletion of approximately 1.5 kb. Mutagenesis of the wild-type
      region with a miniMu transposon and complementation analysis showed that the
      mutation in ccmB, and not the deletion, was responsible for the phenotype of
      CFN4201 strain and that ccmA and ccmB are independent transcription units. We
      found that a region located downstream of ccmB is reiterated twice, one near the
      chromosomal ccmA-ccmB locus while the second in plasmid e. Finally, CFN4201
      membranes had detectable levels of C1 apoprotein which did not contain bound
      haem. This data could suggest that haem binding to the apoprotein occurs after
      the translocation of the apo form of c1 to the membrane.

PMID- 8982079
TI  - Isolation, sequencing and overproduction of the single-stranded DNA binding
      protein from Pseudomonas aeruginosa PAO.
AB  - The gene (ssb) encoding the single-stranded DNA binding (SSB) protein from
      Pseudomonas aeruginosa PAO was detected on a 2.1 kbp PstI-fragment of chromosomal
      DNA. The protein (PaeSSB) encoded by this gene consists of 165 aa and has a M(r)
      of 18549. The genomic sequence was confirmed by amino acid sequencing of the
      amino terminus of SSB protein isolated from P. aeruginosa PAO. PaeSSB shows 68%
      homology to the respective protein of E. coli. The nucleotide sequence upstream
      of the P. aeruginosa ssb gene shows little homology to the regulatory region
      upstream of the ssb gene of E. coli. The ssb gene was located at a distance of
      690-870 kbp from the origin of replication on a physical map of P. aeruginosa
      PAO. In vivo PaeSSB could replace the SSB protein of E. coli (EcoSSB) if its
      production was controlled by the lac promoter on a high-copy vector. PaeSSB was
      overproduced in E. coli. Both the overproduced protein and PaeSSB isolated from
      Pseudomonas aeruginosa PAO are post-translationally modified by cleavage of the
      first methionine. Analytical ultracentrifugation shows that PaeSSB is a stable
      homotetramer. The copy number of PaeSSB in P. aeruginosa is 1200 +/- 250
      tetramers per cell. Preliminary characterization of the DNA binding properties
      shows PaeSSB to have a lower affinity for single-stranded DNA than EcoSSB.

PMID- 8982080
TI  - Development of a VSV-G protein pseudotyped retroviral vector system expressing
      dominant oncogenes from a lacO-modified inducible LTR promoter.
AB  - We report the development of a retroviral vector system in which two dominant
      oncogenes are expressed inducibly in human cells using the lac repressor/lac
      operator regulatable promoter system. First, the parent vector, pLoCRNLo, was
      constructed to contain a retroviral long terminal repeat (LTR) promoter that has
      been modified by incorporation of a lac operator sequence (lacO). This promoter,
      LTRo, was shown to mediate IPTG-inducible cat expression in rat cells expressing
      the lac repressor. The pLoCRNLo backbone was used to develop the retroviral
      vector LoTPRRNLo which expresses SV40 T antigen and H-ras val12 oncogenes as a
      dicistronic unit separated by a poliovirus internal ribosome entry sequence (PO
      IRES). LoPRRNLo retrovirus was produced as a VSV-G protein pseudotype and used to
      infect primary human cells, resulting in the efficient formation of transformed
      cell lines. Subsequent introduction into the transformed cells of the lac
      repressor, expressed from a second retroviral vector, MSCV-In(S), resulted in
      IPTG-responsive oncogene expression and cell growth. This vector system is useful
      for introducing multiple genes under inducible control into mammalian cells.

PMID- 8982081
TI  - Sequence variation of a hypervariable short tandem repeat at the D12S391 locus.
AB  - A short tandem repeat (STR) in the D12S391 locus was sequenced in more than 40
      individuals. Twenty different alleles were found and these could be grouped into
      12 allelic classes in accordance with the total number of repeats. This is a
      compound STR consisting of blocks of (AGAT) and (AGAC) repeats with basic
      sequence structure (AGAT)8-17(AGAC)6-10(AGAT)0-1. Whereas smaller alleles (15-18)
      have variation limited to the (AGAT) unit, in larger alleles the complexity is
      greater with variation in the number of tandem arrays in the two motifs (AGAT)
      and (AGAC). Population data showed that this is a highly polymorphic STR with a
      heterozygosity of more than 0.9. This fact, together with its simple structure,
      makes this STR an interesting DNA polymorphism for forensic and genetic purposes.

PMID- 8982082
TI  - Cloning and characterization of a cDNA for rat CD30 homolog and chromosomal
      assignment of the genomic gene.
AB  - CD30 is a member of the tumor necrosis factor receptor superfamily, which is
      expressed on some activated lymphocytes, virus-infected cells and transformed
      lymphocytes. To facilitate our understanding of biological functions and
      functional domains, we isolated rat cDNA clones encoding the rat homolog of human
      CD30 from a cDNA library of a rat T-cell line, TARL-2. The nucleotide sequence of
      the cDNA showed 73% homology with that of human CD30. The deduced rat CD30
      protein consisted of 493 amino acids with an M(r) of 59 160 and contained a
      single transmembrane domain. It lacked the second repeat of the cysteine-rich
      motif in the extracellular domain found in human CD30. The amino acid sequence
      showed 51.8 and 61.2% identity with the cysteine-rich and the cytoplasmic
      domains, respectively. In the cytoplasmic domain, however, the amino acid
      sequence was highly conserved in about 100 residues near the C-terminus showing
      77.7% identity, whereas the rest of the cytoplasmic domain showed 45.2% identity.
      This conservation suggests the functional importance of this region. Comparison
      with the recently reported mouse CD30 revealed 83.7% conservation of the amino
      acid sequence and a common structure of the extracellular domain which lacks the
      second cysteine-rich motif. Northern blots revealed a 3.4-kb mRNA in the PHA
      activated spleen cells and human T-cell leukemia virus type 1 (HTLV-1)-infected
      rat T-cell lines, whereas smaller transcripts of 2.3 kb were found in the lung. A
      rabbit polyclonal antibody raised against GST-fusion protein of the cytoplasmic
      domain detected bands with an apparent M(r) of 80 kDa and 100- 110 kDa expressed
      in TARL-2 and spleen cells. Transient overexpression of rat CD30 in TARL-2 cells
      activated HIV LTR in a NF-kappa B site-dependent manner, indicating that CD30
      signals activate NF-kappa B. The chromosomal location of the gene was identified
      by fluorescence in situ hybridisation at 5q36.2, and appeared to correspond to
      human 1p36, where human CD30 has been mapped. The identification and
      characterization of the rat counterpart of human CD30 will facilitate studies of
      the biological function of this molecule.

PMID- 8982083
TI  - Characterization of engF, a gene for a non-cellulosomal Clostridium cellulovorans
      endoglucanase.
AB  - A new Clostridium cellulovorans (strain ATCC 35296) endoglucanase gene engF has
      been isolated and sequenced. The gene contains 1671 bp and codes for a protein
      containing 557 amino acids and a mass of 60.1 kDa. A putative signal peptide of
      29 amino acids is present and the mature protein has a mass of 57.1 kDa. EngF
      does not have amino acid sequence homology to previously isolated EngB and EngD,
      but does show sequence homology to family 5 glycosyl hydrolases from Bacillus,
      Erwinia carotovora, and C. acetobutylicum species. EngF is not a component of the
      cellulosome and does not contain a duplicated sequence (DS) at its C-terminal
      region. EngF is capable of binding to cellulose and hydrolyzing
      carboxymethylcellulose but not xylan. The cellulose binding domain (CBD) differs
      from types I, II and III CBDs and no obvious homology has been found to other CBD
      types. The maximum activity of EngF occurs at pH 5.5 and at 47 degrees C. Its
      properties suggest that EngF plays an ancillary role in the degradation of
      cellulosic materials.

PMID- 8982084
TI  - Molecular cloning and characterization of a cDNA that encodes protoporphyrinogen
      oxidase of Arabidopsis thaliana.
AB  - A cDNA encoding protoporphyrinogen oxidase (PPOX), the last enzyme common to the
      biosynthetic pathways for chlorophylls and hemes, was obtained from a library of
      Arabidopsis thaliana cDNA constructed in a lambda vector by screening for
      complementation of a hemG mutant of Escherichia coli. Extracts of E. coli cells
      transformed with the Arabidopsis PPOX cDNA had high PPOX activity, and this
      activity was markedly inhibited by acifluorfen, a specific inhibitor of PPOX.
      Sequence analysis revealed that the cDNA for Arabidopsis PPOX encodes a protein
      of 537 amino acids (aa) with a calculated molecular mass of 57.7 kDa. The deduced
      aa sequence exhibited similarity to sequences of PPOX from Bacillus subtilis,
      mouse, and human. However, the PPOX of Arabidopsis contained a putative leader
      peptide for import into mitochondria (mt). southern analysis indicated that the
      PPOX whose cDNA we cloned is encoded by a single gene in Arabidopsis. Northern
      blot analysis showed that the level of expression of the gene in Arabidopsis
      leaves was high. whereas it was low in roots and floral buds. To our knowledge,
      this is the first report for the cloning of a cDNA for a plant PPOX.

PMID- 8982085
TI  - Insertion of metal-responsive elements increases the inducibility of the mouse
      mammary tumor virus promoter.
AB  - The promoter of the mouse mammary tumor virus (MMTV) is commonly used in
      inducible mammalian expression vectors. We have modified this promoter by
      inserting metal-responsive elements (MRE) at different sites. Surprisingly, MMTV
      promoters containing MRE 5' with respect to the glucocorticoid responsive
      elements (GRE), were not induced by metal ions. However, in the simultaneous
      presence of dexamethasone and metal ions, the modified promoters displayed a
      significantly increased transcriptional strength [up to sevenfold more than wild
      type (wt) MMTV] in transiently transfected cells and permanent cell lines. This
      increment in the inducible expression was achieved without a concomitant increase
      in the basal level of expression. These modified MMTV promoters will offer the
      opportunity to develop tightly regulated inducible mammalian expression systems
      that are significantly more potent than the ones based on the wt MMTV promoter.

PMID- 8982086
TI  - Characterization of a polyubiquitin gene in T. thermophila and of ubiquitin gene
      expression during sexual reproduction and under stress conditions.
AB  - A 5-unit polyubiquitin gene, TTU3, was isolated from a T. thermophila genomic
      library and sequenced. This gene presents an extra triplet coding for Phe, a
      AGAGA motif and a putative HSE element in its 5'-non-coding region. The ubiquitin
      gene expression in this ciliate was investigated by Northern blot hybridization
      in conjugating cells or cells under stress conditions. Exponentially growing
      cells express two ubiquitin mRNAs of 0.75 and 1.8 kb and a new species of 1.4 kb
      is induced under hyperthermic stress. During sexual reproduction of the cells
      (conjugation) the 1.8-kb mRNA is still transcribed whereas the steady-state
      population of the 0.75 mRNA transcripts is strongly diminished. Southern blot
      analysis suggests that ubiquitin in T. thermophila constitutes a large family of
      about ten members.

PMID- 8982087
TI  - Organisation of the tmb catabolic operons of Pseudomonas putida TMB and
      evolutionary relationship with the xyl operons of the TOL plasmid pWW0.
AB  - In Pseudomonas putida (Pp) TMB the genes involved in the catabolism of methyl
      substituted aromatic hydrocarbons 1,2,4-trimethylbenzene, m- and p-xylene (tmb
      operon), are functionally and genetically homologous to the xyl genes of the
      plasmid pWW0, but are chromosomally encoded. We have analysed by cloning.
      Southern blotting and sequencing of selected regions the organisation of the tmb
      cluster. This analysis shows that the structural and regulatory genes of the tmb
      and xyl systems exhibit a high degree of homology and are similarly organised in
      operons. However the operons are differently arranged on the Pp TMB chromosome
      and on the pWW0 plasmid. Comparison of the two systems suggests that the operon
      arrangement found in pWW0 may have originated from that found in Pp TMB via
      cointegration mediated by replicative transposition or by intermolecular
      recombination between two copies of the insertion element IS1246.

PMID- 8982088
TI  - Characterization of a tRNA(Lys)(CUU) gene located in the opposite orientation
      upstream of a ZmFer2 ferritin gene in the maize nuclear genome.
AB  - The first evidence for a plant tRNA(Lys)(CUU) gene is reported. This gene is
      found closely linked 400 bp upstream, and on the complementary strand, of a
      ZmFer2 ferritin gene in the maize nuclear genome. Southern blot analysis
      indicates that this tRNA(Lys) is a member of a multigene family. This gene does
      not contain any intron, and exhibits classical intragenic regulatory elements
      found in eukaryotic tRNA genes (A and B boxes). Moreover, 5' and 3'-flanking
      sequences display typical features found in nuclear encoded tRNAs. The deduced
      mature tRNA sequence is almost identical to the sequence of a cytoplasmic
      tRNA(Lys)(CUU) from wheat germ. The maize tRNA(Lys) gene is expressed in vivo in
      maize and in transgenic tobacco, as shown by RT-PCR analysis.

PMID- 8982089
TI  - Characterization of the nuclear localization signal and subcellular distribution
      of hepatitis C virus nonstructural protein NS5A.
AB  - Hepatitis C virus (HCV) has a positive strand RNA genome that codes for a
      polyprotein that is processed co-translationally and post-translationally into
      three structural and at least seven nonstructural (NS) proteins. To investigate
      the function of NS5A, a recombinant vaccinia virus was constructed in which the
      NS5A gene was cloned under the control of T7 promoter and encephalomyocarditis
      virus 5'-untranslated region (EMCV-UTR) for cap-independent translation in
      mammalian cells. In addition, the NS5A gene was also cloned under the control of
      cytomegalovirus (CMV) early promoter. The NS5A expressed in monkey kidney (CV-1)
      cells was located predominantly in the cytoplasm. Using immunohistochemical
      analysis, the subcellular distribution of NS5A in liver biopsy samples from
      chronic HCV-infected patients was also found to be in the cytoplasm. However, the
      NS5A protein has a stretch of positively charged domain in the vicinity of
      proline and valine residues, (PPRKKRTVV), characteristic of a nuclear
      localization signal (NLS), in the COOH-terminal half of the protein. To
      investigate whether the putative NLS of NS5A is functional, chimeric expression
      plasmids were constructed in which regions containing the NLS were fused to the N
      terminus of the E. coli beta-galactosidase (E. coli beta-Gal). The expression of
      the fusion proteins in CV-1 cells resulted in their nuclear localization,
      indicating that the putative NLS is functional in targeting the heterologous
      protein, E. coli beta-Gal, to the nucleus, although the native NS5A is retained
      in the cytoplasm.

PMID- 8982090
TI  - Molecular characterization of the pigeon P-opsin gene.
AB  - The chicken gene encoding pineal gland-specific opsin (P-opsin) has been
      previously characterized. We report here the orthologous pigeon (Columba livia) P
      opsin gene. The deduced pigeon P-opsin lacks a potential N-glycosylation site in
      the N-terminus, but has multiple phosphorylation sites in the C-terminus, which
      are opposite from the characteristics of the chicken P-opsin.

PMID- 8982091
TI  - Amide metabolism: a putative ABC transporter in Rhodococcus sp. R312.
AB  - The DNA sequence has been determined upstream of the amiE structural gene in the
      amidase operon of Rhodococcus sp. R312 and a new ORF (amiS2) identified. The
      amiS2 gene encodes a potential 206 amino acid (aa) protein containing a high
      proportion of hydrophobic residues. The AmiS2 protein possesses high homology to
      the ORFP3, amiS and ureI gene products from the Mycobacterium smegmatis (Ms)
      acetamidase operon, Pseudomonas aeruginosa (Pa) amidase operon and Helicobacter
      pylori (Hp) urease operon, respectively. Hydropathic analysis and secondary
      structure prediction of AmiS2 suggested the presence of seven potential
      transmembrane (TM) alpha-helices. Sequence analysis of the amiB2 gene, located
      downstream of the Rhodococcus sp. R312 amiE gene, showed that it encoded a 351-aa
      protein containing a potential ATP-binding motif. AmiB2 showed significant
      homology with the ATP-binding subunit of the bacterial Clp protease and high
      homology with the amiB product located within the Pa amidase operon. AmiB2 and
      AmiS2 appear to be two components of a recently identified novel family of ABC
      transporters (Wilson et al., 1995) and might be responsible for the adsorption of
      amidase substrates or release of their hydrolysis products.

PMID- 8982092
TI  - Revised nucleotide sequence of an archaeal insertion element (ISH28) reveals a
      putative transposase gene.
AB  - The published sequence of the insertion element ISH28 contained many small ORFs
      that were difficult to interpret. We resequenced the entire element and found
      seven nucleotide differences. The corrected sequence of ISH28 is 938 bp long, and
      now reveals a single open reading frame of 828 bp. The putative protein is highly
      similar (49% aa identity) to the predicted transposase of ISH1.

PMID- 8982093
TI  - Phylogenetic distribution of the global regulatory gene csrA among eubacteria.
AB  - The gene csrA encodes a unique kind of global regulator, CsrA, which modulates
      glycolysis, gluconeogenesis, glycogen biosynthesis and glycogen catabolism in
      Escherichia coli. Southern hybridization and nucleotide sequencing data have
      revealed apparent csrA homologs within several families of the alpha and gamma
      subdivisions of the proteobacteria (purple bacteria) and in the Gram-positive
      bacterium Bacillus subtilis. Thus, the CsrA regulatory system appears widely
      distributed among eubacteria.

PMID- 8982094
TI  - Analysis of the urease gene complex of members of the genus Yersinia.
AB  - The urease gene complex of Yersinia enterocolitica is relatively conserved within
      the species, although this conservation may not extend to other members of the
      genus. Spontaneous urease-negative isolates of Y. enterocolitica appear to have
      arisen as a result of large deletions within this complex, while Y. pestis shows
      no significant deletions within the complex, despite being urease negative.

PMID- 8982095
TI  - A novel plasmid vector that uses the glucose kinase gene (glkA) for the positive
      selection of stable gene disruptants in Streptomyces.
AB  - We describe an Escherichia coli plasmid, pIJ2581, that can be used for the
      efficient construction of stable gene disruptants and of gene deletions in
      Streptomyces. Integration of pIJ2581 derivatives carrying chromosomal sequences
      is achieved by selecting for plasmid-encoded thiostrepton resistance, while
      plasmid excision is secured by counter-selection of the pIJ2581 glkA gene, which
      confers sensitivity to 2-deoxyglucose.

PMID- 8982096
TI  - Prior exposure to superantigen can inhibit or exacerbate autoimmune
      encephalomyelitis: T-cell repertoire engaged by the autoantigen determines
      clinical outcome.
AB  - Experimental allergic encephalomyelitis (EAE) is inducible in experimental
      animals immunized with myelin basic protein (MBP), proteolipid protein (PLP) or
      their peptides. We compared T-cell responses to encephalitogenic epitopes of
      PLP(43-64) and MBP(Ac1-11) in a single mouse strain, (PL/J x SJL)F1. MBP(1-11)
      specific T-cell hybridomas expressed predominantly TCR V beta 8 or V beta 4,
      while PLP(43-64)-specific hybridomas expressed a diverse TCR repertoire. To
      analyze the biologic significance of the TCR repertoire (limited vs. diverse) to
      disease susceptibility, we pretreated mice with a superantigen (SEB), and then
      induced disease with these autoantigens. Mice injected with SEB and immunized
      with MBP(Ac1-11) showed significant inhibition of EAE, whereas SEB-pretreated
      mice immunized with PLP(43-64) had an increased severity of EAE and developed a
      chronic disease. These data demonstrate that prior exposure to microbial
      superantigens can significantly alter the autoimmune disease course depending
      upon the TCR repertoire used by the autoantigen.

PMID- 8982097
TI  - Recombinant human interleukin 1 beta induces production of prostaglandins in
      primary human fetal astrocytes and immortalized human fetal astrocyte cultures.
AB  - Astrocytes play an important role in initiating and modulating inflammatory
      responses within the central nervous system. Extensive studies in rodents have
      shown that TPA, substance P, calcium ionophore A21387, and lipopolysaccharide
      (LPS) induce formation and release of arachidonic acid metabolites which have
      immunoregulatory properties. To better understand the immunopathology of brain
      injury, we studied the role of inflammatory cytokines such as tumor necrosis
      factor alpha, interleukin (IL) 6, IL-2, interferon gamma and IL-1 beta in the
      production of arachidonic acid metabolites in cells from fetal human brain. Among
      these cytokines, only IL-1 beta significantly stimulated production of
      prostaglandins E2 and F2 alpha but not PGD2, thromboxane B2 and 6-keto-PGF1
      alpha. Under our experimental conditions, these astrocyte cultures did not
      produce metabolites in the lipoxygenase pathway such as leukotrienes B4 and C4
      upon IL-1 beta stimulation. The stimulatory effects of IL-1 beta on the induction
      of arachidonic acid metabolites have been studied in various human cell types but
      not in astrocytes. Human astrocyte production of PGF2 alpha and PGE2 but not
      PGD2, 6-keto-PGF1 alpha and TXB2 when stimulated by IL-1 beta, is thus a novel
      finding. This observation should initiate investigations into the mechanism of
      arachidonic acid metabolism and the role of its metabolites in inflammation in
      the human nervous system.

PMID- 8982098
TI  - Binding of alpha-adrenergic receptors stimulates the anti-mycobacterial activity
      of murine peritoneal macrophages.
AB  - The effects of adrenergic stimulation of the anti-mycobacterial activity of
      peritoneal macrophages was investigated. We found that epinephrine and
      norepinephrine stimulated macrophages to suppress the growth of Mycobacterium
      avium. Stimulation was mediated by binding to the alpha 2 adrenergic receptor.
      The addition of the alpha 2 agonist clonidine to cultures resulted in an
      inhibition of mycobacterial growth and the effect of epinephrine was blocked by
      the alpha-antagonist phentolamine. Treatment of the macrophages with propranolol,
      a beta-antagonist, potentiated the effect of epinephrine. Epinephrine mediates
      its effect by stimulating the expression of macrophage activation genes.

PMID- 8982099
TI  - Differential effects of gastrin-releasing peptide, neuropeptide Y, somatostatin
      and vasoactive intestinal peptide on interleukin-1 beta, interleukin-6 and tumor
      necrosis factor-alpha production by whole blood cells from healthy young and old
      subjects.
AB  - In the present study, we have investigated the effect in vitro of gastrin
      releasing peptide (GRP, 10(-10) M), neuropeptide Y (NPY, 10(-10) M), somatostatin
      (10(-10) M) and vasoactive intestinal peptide (VIP, 10(-9) M) on the production
      of IL-1 beta, IL-6 and TNF alpha by peripheral whole blood cells from healthy
      young and old people. We have found that GRP, NPY, somatostatin and VIP
      stimulated the production of IL-1 beta in old subjects, and NPY, somatostatin and
      VIP in young ones. In addition, the production of IL-6 was enhanced by GRP, NPY
      and VIP in young and old people. The TNF alpha production was stimulated by NPY
      and somatostatin in young subjects, and by NPY, somatostatin and VIP in old ones,
      whereas GRP produced a decrease of TNF alpha in young persons. GRP in old
      subjects and VIP in young and old subjects stimulated in a great degree the LPS
      induced IL-6 production by whole blood cells. On the contrary, GRP and VIP
      inhibited highly the LPS-induced TNF alpha production in young controls. Our
      results show that these neuropeptides, when added to whole blood cells at
      physiological concentrations, are able to stimulate the production of IL-1 beta,
      IL-6 and TNF alpha in a differential way according to the subject age.

PMID- 8982100
TI  - Exacerbation of lymphocytic choriomeningitis in mice treated with the inducible
      nitric oxide synthase inhibitor aminoguanidine.
AB  - To elucidate the possible involvement of the inducible nitric oxide synthase
      (iNOS) and NO in the development of lymphocytic choriomeningitis (LCM), the
      consequences of inhibition of iNOS by the inhibitor aminoguanidine was examined
      in mice following intracerebral infection with LCM virus (LCMV). Aminoguanidine
      administration to mice infected with LCMV completely blocked increased plasma
      nitrate/nitrite levels and led to increased proinflammatory cytokine gene
      expression at early stages of lesion development in the brain, enhanced clinical
      severity and decreased survival time. The levels of LCMV recovered from the brain
      of aminoguanidine treated mice did not differ from those in infected control
      mice. These findings argue against either an anti-viral or pathogenic role of NO
      in LCM but rather suggest a possible protective action of this mediator.

PMID- 8982101
TI  - Neuroimmune control of interleukin-6 secretion in the murine spleen. Differential
      beta-adrenergic effects of electrically released endogenous norepinephrine under
      various endotoxin conditions.
AB  - In a previous study we demonstrated a superfusion technique which allows for
      investigation of nerve-immune cell interaction in murine spleen. We demonstrated
      that under septic-like conditions in the presence of bacteria and
      lipopolysaccharide (LPS), electrically induced inhibition of interleukin 6 (IL-6)
      secretion was attenuated by the beta-adrenergic antagonist propranolol. This
      effect was now investigated more closely under various endotoxin conditions in
      order to dissect effects of bacteria and endotoxin: (A) bacteria-rich conditions
      (without penicillin/streptomycin [P/S] and without LPS), (B) LPS-enriched
      conditions (with P/S and with LPS), and (C) bacteria-free conditions (with P/S
      and without LPS). Under bacteria-rich conditions, norepinephrine (Emax = 10(-6)
      M, p = 0.012) and isoproterenol (Emax = 10(-6) M, p = 0.048) concentration
      dependently inhibited IL-6 secretion from murine spleen slices in contrast to
      bacteria-free conditions. In a bacteria-free environment the beta-adrenergic
      antagonist propranolol did not attenuate the electrically induced inhibition of
      splenic IL-6 secretion. The insertion of bacterial filters in front of the
      superfusion chambers to avoid direct contact between bacteria and cells increased
      the electrically-induced inhibition of IL-6 secretion (p = 0.0036). Added LPS did
      not change the electrically-induced release of norepinephrine from presynaptic
      nerve terminals in murine spleen. The study demonstrates two different beta
      adrenergic effects on IL-6 secretion of murine spleen slices under bacteria-rich
      or bacteria-free conditions.

PMID- 8982102
TI  - Age-dependent changes in the expression of dopamine receptor subtypes in human
      peripheral blood lymphocytes.
AB  - The pharmacological profile and the density of dopamine D3 and D5 receptor
      subtypes expressed by human peripheral blood lymphocytes of subjects of different
      ages (ranging from 20 to 75 years) were assessed using radioligand binding
      techniques. Dopamine D3 receptor was assayed with [3H]7-hydroxy-N,N-di-n-propyl-2
      aminotetraline ([3H]7-OH-DPAT) as a ligand. Dopamine D5 receptor was assayed
      using [3HIR]-(+)-(-chloro-2,3,4,5, tetrahydro-5-phenyl-1H-3-benzazepin-al
      hemimaleate) ([3H]SCH 23390) as a ligand. The affinity and the pharmacological
      profile of [3H]7-OH-DPAT and [3H]SCH 23390 at dopamine D3 and D5 receptor,
      respectively, were similar in subjects of different ages. The density of dopamine
      D3 receptor binding sites was slightly decreased in subjects of 30-39 years in
      comparison with younger individuals. A remarkable loss of dopamine D3 receptor
      was then found between 40 and 49 years of age in comparison with younger
      subjects. A further slight decrease was noticeable between 50 and 59 years of
      age. The number of [3H]7-OH-DPAT binding sites was then stabilized after 60 years
      of age. The density of dopamine D5 receptor binding sites did not show age
      dependent changes. The above findings indicate the occurrence of a decline in the
      density of lymphocyte dopamine D3 but not D5 receptor between adult and mature
      subjects. The possibility that dopamine D3 receptor assay in peripheral blood
      lymphocytes may represent a tool for investigating dopamine receptor function in
      aging and age-related neurological disorders is discussed.

PMID- 8982103
TI  - SV40 large T immortalised cell lines of the rat blood-brain and blood-retinal
      barriers retain their phenotypic and immunological characteristics.
AB  - In the central nervous system the blood-brain and blood-retinal barriers (BBB and
      BRB respectively) are instrumental in maintaining homeostasis of the neural
      parenchyma and controlling leucocyte traffic. These cellular barriers are formed
      primarily by the vascular endothelium of the brain and retina although in the
      latter the pigmented epithelial cells also form part of the barrier. From primary
      cultures of rat brain endothelium, retinal endothelium and retinal pigment
      epithelium (RPE) we have generated temperature sensitive SV40 large T
      immortalised cell lines. Clones of brain (GP8.3) and retinal (JG2.1) endothelia
      and RPE (LD7.4) have been derived from parent lines that express the large T
      antigen at the permissive temperature. The endothelial cell (EC) lines expressed
      P-glycoprotein, GLUT-1, the transferrin receptor, von Willebrand factor and the
      RECA-1 antigen and exhibited high affinity uptake of acetylated LDL and stained
      positive with the lectin Griffonia simplicifolia. The RPE cell line was positive
      for cytokeratins and for the rat RPE antigen RET-PE2. All the cell lines
      expressed major histocompatibility complex (MHC) class 1 and intercellular
      adhesion molecule (ICAM)-1 constitutively and could be induced to express MHC
      class II and vascular cell adhesion molecule (VCAM)-1 following cytokine
      activation. The EC also expressed platelet endothelial cell adhesion molecule
      (PECAM)-1. Monolayers of these cells could support the migration of antigen
      specific T cell lines. The generation of immortalised cell lines derived from the
      rat BBB and BRB should prove to be useful tools for the study of these
      specialised cellular barriers.

PMID- 8982104
TI  - Tumor necrosis factor alpha and interleukin-6 mRNA expression in neonatal Lewis
      rat Schwann cells and a neonatal rat Schwann cell line following interferon gamma
      stimulation.
AB  - There is increasing evidence that Schwann cells play an important role in the
      pathogenesis of autoimmune inflammatory peripheral nerve disease. Schwann cells
      have been reported to express major histocompatibility complex class I and II
      (MHC I and II) and intercellular adhesion molecule-1 (ICAM-1), and to produce
      interleukin-1 (IL-1), prostaglandin E2 and thromboxane A2. In this study we
      investigated freshly dissociated neonatal Lewis rat Schwann cells and a SV40
      transfected neonatal rat Schwann cell line (Schwann cell line) for production of
      mRNA for the immunomodulatory cytokines IL-2, IL-4, IL-6, IL-10, interferon-gamma
      (IFN gamma), and tumor necrosis factor-alpha (TNF alpha) employing RT-PCR.
      Primary Schwann cells and Schwann cell line were examined following IFN gamma
      stimulation and were found to express TNF alpha and IL-6 mRNA. These results
      further support a role for Schwann cell participation in inflammatory responses
      within the peripheral nervous system (PNS).

PMID- 8982105
TI  - Substance P augments interleukin-10 and tumor necrosis factor-alpha release by
      human cord blood monocytes and macrophages.
AB  - We have investigated the effects of SP on the constitutive and/or
      lipopolysaccharide (LPS)-induced expression of interleukin-10 (IL-10) and tumor
      necrosis factor (TNF-alpha) in both freshly isolated cord blood monocytes (FICBM)
      and cord blood monocyte-derived macrophages (CBMDM). The cells were treated with
      SP at various concentrations (10(-14) to 10(-6) M) in the presence or absence of
      LPS and culture supernatants were analyzed for IL-10 and TNF-alpha as measured by
      an enzyme immunosorbent assay (ELISA). FICBM and CBMDM treated with SP alone
      increased TNF-alpha secretion. The stimulatory effects of SP on TNF-alpha
      secretion are inhibited by a anti-SP polyclonal antibody and SP antagonists,
      spantide ([D-Arg-1-D-Trp-7-D-Trp-9-Leu-11]-SP) and CP-96,345 (a nonpeptide
      antagonist of the SP receptor). Although the treatment with SP alone did not
      enhance IL-10 secretion by both freshly isolated and cultured cord monocytes,
      treatment with SP in combination with LPS leads to a synergistic interaction in
      upregulation of IL-10 secretion. Fragments of SP (SP1-4 and SP5-11) in the
      presence or absence of LPS show little effects on IL-10 secretion by FICBM. SP
      reverses the inhibitory effect of IFN-gamma on LPS-induced IL-10 secretion by
      FICBM. In addition, the two SP antagonists and the anti-SP polyclonal antibody
      blocked the SP effect on IL-10 secretion by FICBM, indicating that these effects
      are specific and SP receptor mediated. Thus, SP is likely to play an important
      role in certain inflammatory conditions in the immune and nervous systems.

PMID- 8982106
TI  - Expression of CD43 in human microglia and its downregulation in Alzheimer's
      disease.
AB  - CD43 (leukosialin, sialophorin) expression in brain tissue of neurologically
      normal and Alzheimer disease (AD) cases was studied immunohistochemically.
      Abundant CD43-like immunoreactivity was detected in ramified microglia of normal
      brain. It was also seen in residual leukocytes in capillaries and was faintly
      detectable on the surface of some normal appearing neurons. In AD brains, the
      overall expression of CD43 by microglia was markedly lower than in control
      brains. This was in contrast to HLA-DR which was sharply upregulated due to the
      activated state of the microglia. This is the first report of a microglial marker
      which is more highly expressed in the resting or ramified state. Such expression
      is consistent with theories that CD43 plays an anti-adhesional role, and that
      cleavage occurs during cellular activation.

PMID- 8982107
TI  - Restricted T cell receptor repertoire for acetylcholine receptor in murine
      myasthenia gravis.
AB  - Immunization of C57BL/6 mice with AChR provokes symptoms similar to those seen in
      the disease myasthenia gravis. To elucidate the structural requirements for T
      cell recognition of AChR and to identify TcR features which might provide targets
      for immunotherapy, a panel of T cell hybridomas was generated after immunization
      of mice with the immunodominant peptide of the AChR alpha chain. The TcR genes
      expressed by these hybridomas were sequenced. TcR-V beta 6 was preferentially
      employed, but other V beta genes were also observed. A conserved acidic residue
      was present in all CDR3 regions, regardless of the V beta. The TcR-V alpha
      repertoire was somewhat skewed with three V alpha families accounting for 82% of
      the sequences. The utilization of multiple T cell receptor V beta genes may
      contribute to the inability to inhibit EAMG by elimination of V beta 6+ T cells.

PMID- 8982108
TI  - Complement expression on astrocytes and astrocytoma cell lines: failure of
      complement regulation at the C3 level correlates with very low CD55 expression.
AB  - Primary fetal human astrocytes and an astrocytoma cell line, U373-MG, expressed
      membrane cofactor protein (CD46), CD59, and low levels of decay-accelerating
      factor (CD55). Astrocyte CD55 was capable of regulating C3 deposition on the cell
      surface; albeit at a lower level than primary human fibroblasts. Negligible
      complement-mediated lysis of primary astrocytes and the U373-MG cell line was
      observed, even when large amount of astrocyte-specific, complement-activating
      antibodies were bound to the cells. Blocking the function of CD59 on astrocytes
      resulted in a > 90% cell lysis, while equivalent lysis of fibroblasts could only
      be achieved with additional blocking of CD55.

PMID- 8982109
TI  - Myocardial ischemia alters immunoregulatory cell traffic and function in the rat
      independent of exogenous catecholamine administration.
AB  - Recent investigation has suggested there is an adrenergically-driven efflux of
      beta 2-receptor rich lymphocyte subsets into the circulation with altered
      function following either exercise or infusion of exogenous catecholamines.
      Myocardial ischemia, like exercise, is associated with generalized
      sympathoadrenal activation. To determine whether ischemia influences
      immunoregulatory cell traffic and function in a manner comparable to beta 2
      adrenergic stimulation via isoproterenol, rats underwent thoracotomy with or
      without coronary ligation. Another group of rats received either isoproterenol (1
      mg/kg) or vehicle (10 mM HCl) intraperitoneally. Thoracotomy, regardless of
      whether or not myocardial ischemia was induced, led to lymphocytosis, reflected
      primarily by an increase in Thelper (Th) cells and, to a lesser degree, in
      Tsuppressor/cytotoxic (Ts/c) and natural killer (NK) cells, with a tendency
      toward an increased Th/Ts/c ratio. To the contrary, isoproterenol injection
      resulted in a relative lymphopenia characterized by diminished B and Th cell
      numbers, preserved Ts/c and increased NK cell numbers leading to a significant
      decrease in the Th/Ts/c ratio. With respect to splenic composition, 60 but not 15
      min of myocardial ischemia led to diminished Th and B cell numbers compared to
      sham operated controls, whereas isoproterenol appeared to stimulate an efflux of
      only NK cells. Both ischemia and isoproterenol enhanced basal splenocyte
      function; however, only ischemia significantly boosted splenocyte responsiveness
      to the mitogen Concanavalin A. Surgically induced myocardial ischemia leads to
      alterations in immunoregulatory cell migration and function which are distinct
      from those found with beta 2-adrenergic stimulation via isoproterenol.

PMID- 8982110
TI  - Glial transforming growth factor (TGF)-beta isotypes in multiple sclerosis:
      differential glial expression of TGF-beta 1, 2 and 3 isotypes in multiple
      sclerosis.
AB  - We studied glial transforming growth factor (TGF)-beta isotype expression in 14
      cases of multiple sclerosis. Acute active lesions exhibited selective TGF-beta 2
      immunoreactivity of lesion encircling ramified microglia. In contrast, astrocytes
      within chronic active white matter lesions expressed all three isotypes. Chronic
      active lesions which extended into cortex exhibited selective cortical astrocyte
      TGF-beta 2 expression. This isotype was also selectively expressed by astrocytes
      in apparently normal white matter. A similar pattern of glial TGF-beta expression
      was seen in the pathological control, progressive multifocal leukoencephalopathy.
      The results suggest that TGF-beta cytokines are locally expressed in
      demyelination and that the beta 2 isotype may be uniquely regulated.

PMID- 8982111
TI  - Increased Fas antigen on T cells in multiple sclerosis.
AB  - Programmed cell death of antigen specific T cells (apoptosis) may be an important
      process in the pathogenesis of autoimmune diseases such as multiple sclerosis
      (MS). Fas antigen was recognized as an apoptosis-related antigen. To investigate
      Fas antigen in multiple sclerosis (MS), we measured the expression rate of Fas
      antigen and activation markers on T cells in peripheral blood (PB) of 19 MS
      patients, 18 controls and in cerebrospinal fluid (CSF) of nine MS patients by
      flow cytometry. The positive rate of Fas antigen in MS patients was higher than
      that of healthy controls in PB. In patients with MS, the expression rates of Fas
      antigen and activation markers were higher in CSF than in PB. The above findings
      suggest that there is acceleration or impairment of apoptosis on activated T
      cells in MS.

PMID- 8982112
TI  - Suppression of cell-transferred experimental autoimmune encephalomyelitis in
      defibrinated Lewis rats.
AB  - The role of coagulation-fibrinolysis system in experimental autoimmune
      encephalomyelitis (EAE) was studied by using batroxobin, derived from the venom
      of the South American pit viper Bothrops atrox moojeni. Batroxobin converts
      circulating fibrinogen into an insoluble form and causes a profound degree of
      afibrinogenemia. Batroxobin treatment (30 BU/kg/day) suppressed clinical signs of
      cell transferred EAE; the mean cumulative clinical score for batroxobin treated
      rats was 3.97, while saline treated controls scored 6.9 (P < 0.01). Plasma
      fibrinogen concentration decreased significantly in batroxobin-treated rats.
      Histologically, the degree of perivascular mononuclear cell infiltration in the
      spinal cord was not suppressed in batroxobin-treated rats compared to saline
      treated control rats, however, deposition of fibrin around the vessels in the
      spinal cord was markedly suppressed in batroxobin-treated rats. These findings
      suggest that batroxobin suppresses EAE by preventing fibrin deposition, and
      provide evidence that CNS-associated deposition of fibrin and ensuing
      fibrinolysis, together with increased permeability of blood brain barrier (BBB),
      are related prerequisites for the clinical manifestation of EAE.

PMID- 8982113
TI  - Identification of dopamine D4 receptor mRNA in circulating human lymphocytes
      using nested polymerase chain reaction.
AB  - There is a long standing controversy if dopamine receptors are present on human
      lymphocytes. In recent years the expression of dopamine D3 and D5 receptors was
      demonstrated with molecular biological methods. Using reverse transcription and
      polymerase chain reaction (RT-PCR) we were able to demonstrate the expression of
      the dopamine D4 receptor (DRD4) mRNA in human circulating lymphocytes. Direct
      sequencing of the RT-PCR product assured that it corresponds to the human DRD4
      sequence. However, because of the unusual high G/C content of the DRD4, several
      precautions have to be applied for reliable results.

PMID- 8982114
TI  - Inducible nitric oxide synthase gene expression and enzyme activity correlate
      with disease activity in murine experimental autoimmune encephalomyelitis.
AB  - Messenger RNA encoding inducible NO synthase (iNOS) was measured by competitive
      reverse transcriptase polymerase chain reaction (cRT-PCR) and ribonuclease
      protection assays in spinal cords from mice at varying stages of experimental
      allergic encephalomyelitis (EAE) and from control mice. iNOS mRNA was increased
      in spinal cords from mice with acute EAE. cRT-PCR assays revealed a 10-20-fold
      increase in iNOS mRNA in spinal cords during acute EAE compared with the level
      observed in normal mouse spinal cords. Functional iNOS activity, as assessed by
      assay of calcium-independent citrulline production, was also significantly
      increased in spinal cords from mice with acute EAE in comparison to normal
      controls. The correlation of functional iNOS expression with active disease in
      EAE in consistent with a pathogenic role for excess NO in this model of cell
      mediated central nervous system autoimmunity.

PMID- 8982115
TI  - Antibody to GalNAc-GD1a and GalNAc-GM1b in Guillain-Barre syndrome subsequent to
      Campylobacter jejuni enteritis.
AB  - N-Acetylgalactosaminyl GD1a (GalNAc-GD1a) is a proposed target molecule for serum
      antibody in some patients with Guillain-Barre syndrome (GBS) (Kusunoki et al.,
      1994). We examined autoantibody to GalNAc-GD1a in sera from 58 GBS patients.
      Eight GBS patients had high IgG anti-GalNAc-GD1a antibody titers, 3 of whom also
      had high IgM anti-GalNAc-GD1a antibody titers. These 8 patients had experienced
      gastrointestinal infection before the onset of their neurological symptoms.
      Campylobacter jejuni was isolated from 4 of them. An absorption test indicated
      the presence of the GalNAc-GD1a epitope in lipopolysaccharides of C. jejuni. Sera
      that had anti-GalNAc-GD1a antibody reacted with several acidic glycolipids in
      bovine peripheral nerve, one of which was identified as N-acetylgalactosaminyl
      GM1b (GalNAc-GM1b). Serum binding to GalNAc-GM1b was decreased by absorption with
      GalNAc-GD1a. The presence of GalNAc-GM1b as well as GalNAc-GD1a has been reported
      in human peripheral nerves. We assume that C. jejuni, which bears the [GalNAc
      beta 1-4 (NeuAc alpha 2-3) Gal beta 1-3 GalNAc beta 1-] epitope, is the immunogen
      and that the glycoconjugates with the epitope are target molecules for the
      autoantibody in peripheral nerves of some GBS patients.

PMID- 8982116
TI  - Substance P promotes lymphocyte-endothelial cell adhesion preferentially via LFA
      1/ICAM-1 interactions.
AB  - Substance P (SP), an 11 amino acid peptide, is released by C and A delta sensory
      nerve fibers during tissue insult and inflammation. We investigated the effect of
      SP on the expression and avidity of adhesion molecules, on lymphocytes and
      endothelial cells, which are central to the inflammatory cascade. Using in vitro
      adhesion assays we found that pretreatment of murine endothelial cells with SP
      enhanced their adhesiveness to splenocytes, the murine T cell hybridoma EL4 and
      nylon-enriched primary murine T cells in a dose and time dependent manner, the
      optimum dose being 10(-10) M and the optimum time 6 h. SP at 10(-10) M was also
      able to stimulate the splenocytes, EL4 T cells and primary T cells to enhance
      their adhesiveness for endothelial cells. The increased adhesiveness was
      associated with enhanced expression of ICAM-1 on endothelial cells and increased
      avidity of LFA-1 on lymphocytes. Further SP was chemotactic for T cells. These
      data suggest that SP modulates lymphocyte-endothelial cell interactions by
      preferentially upregulating LFA-1 and ICAM-1 interactions.

PMID- 8982117
TI  - Soluble complement receptor 1 (sCR1) protects against experimental autoimmune
      myasthenia gravis.
AB  - The loss of muscle function seen in myasthenia gravis and in the animal model of
      the disease, experimental autoimmune myasthenia gravis (EAMG) is in part due to
      the activation of complement by anti-acetylcholine receptor (AChR) antibodies at
      the motor end-plate. In this study we describe the effects of a soluble
      recombinant form of human complement receptor 1 (sCR1) on the development of
      clinical disease and receptor loss in EAMG induced passively by administration of
      anti-AChR antibodies. Daily intraperitoneal injection of sCR1 significantly
      reduced the weight loss and severity of clinical symptoms seen and allowed
      treated animals to recover normal muscle function. These data suggest that sCR1
      could provide a useful additional therapeutic agent in myasthenia.

PMID- 8982118
TI  - The antibody repertoire in experimental allergic neuritis: evidence for PMP-22 as
      a novel neuritogen.
AB  - Experimental allergic neuritis (EAN) is an autoimmune disease that serves as an
      animal model for the Guillain-Barre syndrome (GBS). In both disorders there is
      still great uncertainty as to the significance and diversity of autoantibodies
      involved. We focused on the characterization of serum antibody production in
      response to various peripheral nervous system (PNS) myelin proteins during the
      course of actively induced EAN in Lewis rats. These data were compared with EAN
      induced by adoptive transfer of P2-specific CD4+ T cells (AT-EAN) and with
      inoculation with complete Freund's adjuvant (CFA) alone. Semiquantitative Western
      blotting was applied to measure serum IgM and IgG titers against specific myelin
      proteins, including P2, P0, myelin basic protein (MBP), myelin-associated
      glycoprotein (MAG) and PMP-22. Considerable differences in the dynamics of
      antibody titers against individual myelin proteins were observed in active EAN
      and after inoculation with CFA alone. Our data suggest a pathogenic role of IgM
      antibodies against HNK adhesion carbohydrate epitope expressing PNS proteins P0,
      MAG and PMP-22. Among these, PMP-22, a novel candidate neuritogen may be of
      particular relevance. Thus, we provide evidence for the involvement of antibody
      mediated immune response in actively induced EAN and a basis for similar studies
      on related human disorders such as GBS or other demyelinating neuropathies.

PMID- 8982119
TI  - Tumor necrosis factor-alpha, lymphotoxin, interleukin (IL)-6, IL-10, IL-12 and
      perforin mRNA expression in mononuclear cells in response to acetylcholine
      receptor is augmented in myasthenia gravis.
AB  - Myasthenia gravis (MG) is a neuromuscular disorder mediated by autoantibodies
      against the nicotinic acetylcholine receptor (AChR) on the postsynaptic membrane
      of the neuromuscular junction. The production of antibodies is regulated by T
      cells by means of immunoregulatory cytokines. To investigate the involvement of
      TNF-alpha, lymphotoxin (LT), IL-6, IL-10, IL-12 and perforin in MG, numbers of
      cytokine mRNA expressing blood mononuclear cells (MNC) were examined in patients
      with MG and controls. LT belongs to the Th1 cell related cytokines, IL-6 and IL
      10 to the Th2 type, TNF-alpha is produced by both Th1 and Th2 cells, IL-12
      induces T cell switch towards the Th1 type and perforin is an effector molecule
      inducing cell lysis. Short term culture of MNC with AChR revealed augmented
      levels of AChR-reactive TNF-alpha, LT, IL-6, IL-10, IL-12 and perforin mRNA
      expressing cells in MG compared to levels obtained without AChR or in presence of
      control antigen. AChR-reactive TNF-alpha, IL-6, IL-10, IL-12 and perforin mRNA
      expressing cells were higher in MG than controls. These findings suggest that the
      cytokines TNF-alpha, LT, IL-6, IL-10 and IL-12, and the cytolytic effector
      molecule perforin are also involved in MG.

PMID- 8982120
TI  - The HuD paraneoplastic protein shares immunogenic regions between PEM/PSN
      patients and several strains and species of experimental animals.
AB  - Patients with small-cell carcinoma of the lung and paraneoplastic
      encephalomyelitis develop antibodies (anti-Hu) against HuD, a member of a family
      of neuronal specific RNA-binding proteins, which are also expressed by the tumor.
      In order to determine if the human HuD paraneoplastic antigen shares immunogenic
      regions between patients and several strains and species of animals, we immunized
      animals with HuD and several deletion constructs of this protein. All immunized
      animals developed high titers of anti-HuD antibodies, comparable to the antibody
      titers found in paraneoplastic patients. Using immunohistochemistry and Western
      blot analysis of human and mouse cerebral cortex, the pattern of reactivity of
      these antibodies could not be differentiated from the human paraneoplastic anti
      Hu antibodies. None of the immunized animals developed neurologic symptoms.
      Western blot analysis of HuD deletion constructs demonstrated that the first and
      second RNA binding domains were the main immunodominant regions, and that the
      animal immune response was both strain and species dependent.

PMID- 8982121
TI  - Induction of RANTES expression by astrocytes and astrocytoma cell lines.
AB  - The cellular infiltrate found during the acute phase of multiple sclerosis (MS)
      consists of monocytes and activated T cells, suggesting the presence of cell
      specific chemotactic signals during the inflammatory response. We examined the
      ability of human astrocytoma cell lines, as well as primary human and rat
      astrocytes, to generate a specific member of the intercrine/chemokine family of
      cytokines, RANTES, when exposed to TNF-alpha, IL-1 beta and IFN-gamma.
      Astrocytoma cells as well as primary astrocytes produced RANTES upon incubation
      with TNF-alpha or IL-1 beta. IFN-gamma alone did not induce RANTES production by
      astrocytes, but it potentiated the effects of either TNF-alpha or IL-1 beta.
      Induction of RANTES by TNF-alpha was mediated by the p55 receptor since a
      specific anti-p55 antiserum mimicked the effect of TNF-alpha. These results
      indicate that human astrocytes are capable of generating a cell-specific
      chemokine that can account for the inflammatory cellular infiltrate observed
      during the acute phase of MS, in a process that is regulated by cytokines.

PMID- 8982123
TI  - Functional alpha 1-adrenergic receptors on leukocytes of patients with
      polyarticular juvenile rheumatoid arthritis.
AB  - During the last decade it has been shown that the central nervous system can
      influence the immune system. In healthy individuals, catecholamines can inhibit
      the production of pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor
      necrosis factor alpha (TNF-alpha) via interaction with beta 2-adrenergic
      receptors. In contrast, we show here that catecholamines can stimulate the
      production of the interleukin-6 (IL-6) in children with the chronic inflammatory
      disease polyarticular juvenile rheumatoid arthritis (JRA). The induction of IL-6
      is mediated by triggering of alpha 1-adrenergic receptors on peripheral blood
      leucocytes of the patients with polyarticular JRA. Functional alpha 1-adrenergic
      receptors are absent on leukocytes of normal donors and on leukocytes of patients
      with the oligoarticular form of the disease.

PMID- 8982122
TI  - The effect of interferon beta-1b on lymphocyte-endothelial cell adhesion.
AB  - Interferon beta-1b (IFN beta-1b) (Betaseron) has been recently approved for
      treatment of multiple sclerosis (MS), an inflammatory demyelinating disease of
      the central nervous system (CNS). The mechanism of action of IFN beta-1b is not
      understood, but its effect in reducing gadolinium enhanced MRI lesions suggest an
      effect at the blood brain barrier (BBB). Thus the objective of this study is to
      examine the effect of IFN beta-1b treatment of endothelial cells (EC) on
      lymphocyte-EC adhesion, and on the expression of the adhesion molecules (AM) ICAM
      1, VCAM and E-selectin induced by IFN-gamma, TNF-alpha, or IL-1 beta. Primary
      cultures of human umbilical vein EC (HUVEC) were used which under basal
      conditions expressed low levels of ICAM-1 but not VCAM or E-selectin. IFN beta-1b
      (1-1000 IU/ml) had minimal effect on basal expression of AM on HUVEC, but AM
      could be substantially upregulated by IFN-gamma, IL-1 beta or TNF-alpha which was
      associated with a parallel increase in lymphocyte-EC adhesion. The effect of IFN
      beta-1b on AM expression induced by IFN-gamma, IL-1 beta or TNF-alpha was
      slightly additive, and was associated with a modest increase in lymphocyte-EC
      adhesion. In contrast TGF-beta, shown previously to downregulate lymphocyte-EC
      adhesion, inhibited this adhesion in our experiments. It is concluded that IFN
      beta does not downregulate the inducible expression of ICAM-1, VCAM or E-selectin
      on HUVEC and does not inhibit the adhesion of lymphocytes to HUVEC. These
      findings have implications on the mechanism of action of IFN beta-1b in MS.

PMID- 8982124
TI  - Increased in vitro uptake of the complement C3b in the serum of patients with
      Guillain-Barre syndrome, myasthenia gravis and dermatomyositis.
AB  - To examine the role of complement in certain autoimmune neuromuscular diseases,
      we used an in-vitro quantitative complement uptake assay that allows measurement
      of the capacity of patients' sera to deposit fragments of the third complement
      component onto sensitized targets. C3 uptake was significantly higher in patients
      with active dermatomyositis, Guillain-Barre syndrome and myasthenia gravis,
      compared to inclusion body myositis and controls. The in-vitro C3 uptake assay
      supports the role of C3b neoantigen and Membranolytic Attack Complex deposition
      in the target tissues and may be a useful tool to monitor disease activity in
      patients with complement-mediated neurological disorders.

PMID- 8982125
TI  - Long-term study of the biochemistry and biomechanics of anterior cruciate
      ligament-patellar tendon autografts in goats.
AB  - This study examined the change in type-III collagen concentration and
      hydroxypyridinium crosslink density of anterior cruciate ligament-patellar tendon
      autografts and their correlations with Young's modulus of the anterior cruciate
      autografts and anterior cruciate controls for as long as 3 years after surgery.
      Fifteen adult female goats (two control and 13 experimental) were tested. Each
      experimental animal received an anterior cruciate ligament-patellar tendon
      autograft to the right knee. These animals were tested at 0 (n = 2), 6 (n = 2),
      12 (n = 2), and 24 (n = 1) weeks and 1 (n = 3) and 3 (n = 3) years after surgery.
      After mechanical testing, the anterior cruciate autograft and control tissues
      were analysed for type-III collagen concentration and hydroxypyridinium crosslink
      density. The results of sodium dodecyl sulfate gel electrophoresis showed a trend
      of initial increase in the percentage of type-III collagen in the anterior
      cruciate ligament autografts and a subsequent decrease after 24 weeks following
      surgery. There was a nonsignificant (p > 0.05) negative correlation between type
      III collagen concentration and Young's modulus. The hydroxypyridinium crosslink
      density was highest at 1 year after surgery. There was a significant (p < 0.05)
      positive correlation between hydroxypyridinium crosslink density and Young's
      modulus in the anterior cruciate autografts and controls. This suggests that
      hydroxypyridinium crosslink density has a good linear relationship with the
      material strength of the anterior cruciate ligament autograft and hence could be
      used as an objective guide for rehabilitation with anterior cruciate autografts.

PMID- 8982126
TI  - Expression of collagen and matrix metalloproteinases in ruptured human anterior
      cruciate ligament: an in situ hybridization study.
AB  - The biological basis for failure of the human anterior cruciate ligament to heal
      after rupture is unknown. Since this failure could be influenced by abnormalities
      in matrix protein production or degradation, or both, several diverse matrix
      protein markers were utilized to survey the state of these extracellular proteins
      in intrinsic anterior cruciate ligament fibroblasts. Matrix gene expression was
      visualized by in situ hybridization 9 to 365 days after rupture using probes for
      type-I collagen, collagenase, 72kDa-gelatinase, and tissue inhibitor of
      metalloproteinase. Remnants of anterior cruciate ligament were biopsied
      arthroscopically from 20 patients at reconstruction, fixed in 4%
      paraformaldehyde, and processed with cDNA probes for the aforementioned mRNAs.
      mRNA expression of type-I collagen was detected in all specimens, was equally
      distributed throughout the remnants, and remained evident even at 1 year after
      injury. Neither of the matrix-degrading enzymes nor their inhibitor (tissue
      inhibitor of metalloproteinase) was expressed at substantial levels at any time
      point. Collagen expression within the anterior cruciate ligament confirmed the
      viability of the ligament remnants for as long as 1 year after rupture. The lack
      of significant expression of the two matrix-degrading metalloproteinases by the
      fibroblasts is not consistent with an autodegradation of the remaining ruptured
      ligament tissue, and whether the lack of matrix remodelling may account, at least
      in part, for the poor healing response of the anterior cruciate ligament remains
      to be determined. This initial investigation by in situ hybridization techniques
      provides a descriptive profile of matrix gene expression in the damaged human
      anterior cruciate ligament.

PMID- 8982127
TI  - Correlation of bony ingrowth to the distribution of stress and strain parameters
      surrounding a porous-coated implant.
AB  - The ability of shear strains to inhibit bony ingrowth was investigated by use of
      a transcortical porous-coated cylindrical plug implant in a functionally isolated
      turkey ulna model in which the mechanical loading environment could be accurately
      controlled and rigorously defined. The distribution of ingrowth at the bone
      implant interface was quantified following 8 weeks of in vivo loading consisting
      of 100 seconds per day of a 20 Hz sinusoidal stimulus sufficient to cause a local
      peak strain of approximately 100 microstrain in the cortex at the bone-implant
      interface in four turkeys. A nonuniform but repeatable pattern of bony ingrowth,
      from 33 +/- 6 to 72 +/- 6% (mean +/- SE), was observed. The mechanical
      environment in the vicinity of the bone-implant interface was calculated using a
      three-dimensional elastic orthotropic finite element model. The general stress
      strain state of the bone as predicted by the finite element model was validated
      in two additional turkeys using four three-element rosette strain gauges, while
      high resolution moire interferometry was used to determine the mechanical state
      of the region immediately adjacent to the implant itself. Shear strains and
      stresses were evaluated at the interface and correlated to the pattern of bony
      ingrowth circumscribing the implant interface. Linear regressions between
      ingrowth and both shear strain and shear stress were negative, with the values of
      R = -0.75 and R = -0.78 (p < 0.001), respectively, indicating significant
      inhibition of ingrowth where shear components were maximal. These results suggest
      that the minimization of shear stress and strain components is a major
      determinant in achieving successful ingrowth of bone into a prosthesis.

PMID- 8982128
TI  - Osteoblast adhesion to orthopaedic implant alloys: effects of cell adhesion
      molecules and diamond-like carbon coating.
AB  - In total joint arthroplasty, long-term outcomes depend in part on the
      biocompatibility of implant alloys. This study analyzed effects of surface finish
      and diamond-like carbon coating on osteoblast cell adhesion to polished titanium
      aluminum-vanadium and polished or grit-blasted cobalt-chromium-molybdenum alloys.
      Osteoblast binding was tested in the presence and absence of the cell adhesion
      proteins fibronectin, laminin, fibrinogen, and vitronectin and was quantified by
      measurement of DNA content. Although adherence occurred in serum-free medium,
      maximal osteoblast binding required serum and was similar for titanium and cobalt
      alloys at 2 and 12 hours. With the grit-blasted cobalt alloy, cell binding was
      reduced 48% (p < 0.05) by 24 hours. Coating the alloys with diamond-like carbon
      did not alter osteoblast adhesion, whereas fibronectin pretreatment increased
      cell binding 2.6-fold (p < 0.05). In contrast, fibrinogen, vitronectin, and
      laminin did not enhance cell adhesion. These results support the hypothesis that
      cell adhesion proteins can modify cell binding to orthopaedic alloys. Although
      osteoblast binding was not affected by the presence of diamond-like carbon, this
      coating substance may influence other longer term processes, such as bone
      formation, and deserves further study.

PMID- 8982130
TI  - Role of different loading conditions on resorption of hydroxyapatite coating
      evaluated by histomorphometric and stereological methods.
AB  - The role of different loading conditions on resorption of plasma-sprayed
      hydroxyapatite coating was investigated in an experimental study. Resorption of
      hydroxyapatite was quantified by histomorphometric and stereological methods on
      backscattered scanning electron images. Hydroxyapatite-coated titanium implants
      were inserted unilaterally into the medial femoral condyle of the knee in 14
      mature dogs. Initially, all implants were subjected to controlled micromotion of
      150 microns. After 4 weeks, the dogs were randomly assigned either to have the
      implant surgically immobilized to prevent further micromovement or to have a sham
      operation. Sixteen weeks after the first operation, the implants were analyzed.
      Six noninserted implants served as controls. The surface area and volume of the
      hydroxyapatite coating were reduced on the immobilized implants by 53 and 67% (p
      < 0.05), respectively, and were further significantly reduced on the continuously
      loaded implants by 83 and 87%, respectively, compared with the control implants.
      The hydroxyapatite coating was significantly thinner on immobilized (15 microns)
      and continuously loaded (15 microns) implants as compared with control implants
      (23 microns), but no difference between the inserted implants was found. Areas
      not covered with hydroxyapatite had 29 and 24% bone coverage on the immobilized
      and continuously loaded implants (not significant). Resorption of hydroxyapatite
      coating did occur in vivo. Continuous loading of the implants accelerated
      resorption significantly compared with immobilization of the implants. It is
      suggested that completely resorbed hydroxyapatite was partly replaced by bone in
      direct contact with the metal implant surface.

PMID- 8982129
TI  - Response of human osteoblasts to implant materials: integrin-mediated adhesion.
AB  - The initial interaction of the human osteoblast-like cell line Saos-2 with
      orthopaedic implant materials was analyzed to determine the mechanism by which
      these cells adhere to implant surfaces. Saos-2 cells were allowed to attach to
      disks composed of the orthopaedic implant materials Tivanium (Ti6A14V) and
      Zimaloy (CoCrMo) and to control disks of glass and plastic. Serum had no effect
      on the number of cells that attached to Tivanium and Zimaloy at 4 or 24 hours but
      did increase the number of cells that attached to glass at 24 hours. Collagen
      synthesis was determined by [3H]proline incorporation into collagenase-digestible
      protein and noncollagen protein. A significant increase of 19% was found for
      collagen synthesized in cells cultured on Zimaloy for 24 hours compared with
      glass, with no differences on Tivanium and plastic. However, collagenase
      digestible protein and noncollagen protein were increased the most (204 and 198%,
      respectively) on Tivanium compared with glass. To determine if integrins were
      involved in cell attachment to implant materials, the peptide GRGDSP (Gly-Arg-Gly
      Asp-Ser-Pro), which blocks integrin receptors through the Arg-Gly-Asp sequence,
      was added to the cells in serum-free medium. This peptide inhibited cell adhesion
      by 28% on Tivanium and 40% on Zimaloy but had no effect on glass and plastic. The
      control peptide GRADSP (Gly-Arg-Ala-Asp-Ser-Pro) had no effect on adhesion.
      Inhibition of protein synthesis and enzymatic removal of surface proteins did not
      affect the ability of Arg-Gly-Asp peptides to inhibit cell attachment to the
      implant materials. These results suggest that integrins are able to bind directly
      to Tivanium and Zimaloy. Western blot analysis of integrin protein demonstrated
      changes in many integrin subunits, depending on the substrate to which cells
      attached. In particular, the beta 1 integrin subunit was increased 3.8 to 9.5
      fold at 24 hours. To determine specifically which integrins may be involved in
      adhesion, antibodies to integrins were added. An antibody to the fibronectin
      receptor, alpha 5 beta 1, significantly inhibited binding of cells to Tivanium by
      63% and to Zimaloy by 49% and had no effect on glass. The vitronectin receptor
      antibody, alpha v beta 3/beta 5, did not alter cell adhesion. In conclusion,
      osteoblast-like cells appear to be capable of attaching directly to implant
      materials through integrins. The type of substrate determines which integrins and
      extracellular matrix proteins are expressed by osteoblasts. These data provide
      information on how implant materials may affect osteoblast differentiation and
      bone growth.

PMID- 8982131
TI  - Migration of press-fit cups fixed with poly-L-lactic acid or titanium screws: a
      randomized study using radiostereometry.
AB  - The early migration of porous acetabular cups was studied in 43 patients with
      osteoarthrosis. The patients were randomly allocated to additional fixation of
      the cup with either biodegradable poly-L-lactic acid screws or titanium screws.
      Radiostereometric evaluation was done during the first 2 years after the
      procedure in 43 hips (23 with poly-L-lactic acid screws and 20 with titanium
      screws). At the 2-year follow-up, cups fixed with poly-L-lactic acid screws had
      migrated significantly more in the proximal-distal (p < 0.05) and medial-lateral
      (p < 0.05) directions. Cups with titanium screws displayed more pronounced
      rotations around the longitudinal axis (p < 0.05). Postoperatively, on the
      lateral view, there was an increased occurrence of radiolucencies at the dome of
      the cups fixed with poly-L-lactic acid screws (p < 0.05). The clinical result did
      not differ between the two groups. Inferior implant-bone contact in the poly-L
      lactic acid group, local changes of the bone quality, and diminishing support of
      the poly-L-lactic acid screws caused by their degradation with time could be
      reasons for the different pattern of migration observed.

PMID- 8982132
TI  - Effect of noninvasive low intensity ultrasound on bone growth into porous-coated
      implants.
AB  - Noninvasive low intensity ultrasound has been shown to be an effective means of
      accelerating bone fracture healing in both animal and clinical studies. An in
      vivo canine study was designed to determine if noninvasive low intensity
      ultrasound could influence the rate and extent of bone growth into porous-coated
      implants. Twenty-two pairs of fully porous transcortical implants were inserted
      bilaterally into the femora of 12 dogs. In each dog, one femur served as a
      control and the other was subjected to daily ultrasound stimulation for 2, 3, or
      4 weeks. Overall, the ultrasound-stimulated implants demonstrated an 18% increase
      in bone ingrowth compared with their contralateral controls (p = 0.02).
      Noninvasive low intensity ultrasound had its greatest effect in the first 2-3
      weeks of stimulation. At 2 and 3 weeks, the ultrasound-stimulated implants showed
      21 and 16% more ingrowth than their respective contralateral controls. Because
      noninvasive low intensity ultrasound had a positive effect on bone ingrowth in
      this experimental investigation, further research is suggested to assess the
      clinical potential for application to noncemented porous-coated total joint
      replacements.

PMID- 8982133
TI  - Osteogenic potential of allogeneic rat marrow cells in porous hydroxyapatite
      ceramics: a histological study.
AB  - Hydroxyapatite ceramics facilitate osteogenesis but cannot induce bone formation
      by themselves. We studied the feasibility of bone formation supported by
      allogeneic bone marrow cells in porous hydroxyapatite ceramics. Coralline
      hydroxyapatite discs were soaked in a marrow cell suspension harvested from
      either ACI (RT1a), Lewis (RT1(1)), or Fischer 344 (RT1(1v)) male rats, and these
      discs were implanted subcutaneously into 56 male Fischer 344 rats. FK-506
      (tacrolimus hydrate), an immunosuppressant, or saline was injected
      intramuscularly into the recipients every day for 2 weeks after surgery, and
      additional injections were given to 19 of the rats every 2 days for 2 more weeks.
      Neither of the mismatched major (ACI rat) or minor (Lewis rat) marrow cell
      transplants showed any bone formation without administration of FK-506. However,
      in rats treated with FK-506, bone formed in the pores of all the three types of
      ceramics implanted, which each contained the marrow cells from one of the three
      kinds of rats used. There were no differences among the three groups of donors
      with regard to the bone formation ratio. We previously reported that subcutaneous
      implantation of porous hydroxyapatite combined with isogeneic marrow cells
      resulted in consistent bone formation, even at ectopic sites. Since it would be
      difficult to harvest a large number of autologous marrow cells in clinical cases,
      we attempted to use allogeneic marrow cells and have shown the allogeneic murine
      marrow cells to have osteogenic potential.

PMID- 8982134
TI  - Novel animal model for studying the molecular mechanisms of bacterial adhesion to
      bone-implanted metallic devices: role of fibronectin in Staphylococcus aureus
      adhesion.
AB  - Infection around metallic implants is a rare but severe complication of
      orthopaedic surgery. A novel animal model mimicking conditions of internal
      fixation devices was developed to evaluate the role of host proteins adsorbed on
      metallic devices in promoting adhesion and colonization of the material surfaces
      by Staphylococcus aureus. Small plates made of pure titanium were either fixed
      (three screws per plate) onto the iliac bones of guinea pigs or implanted into
      their subcutaneous space as controls. Five to 6 weeks after surgery, the plates
      and screws were removed from the previously killed animals, carefully rinsed in
      buffer, and tested in an in vitro assay of S. aureus adhesion to metallic
      surfaces. To evaluate the role of fibronectin in staphylococcal adhesion to
      explanted plates and screws, a mutant of S. aureus that is specifically defictive
      in fibronectin adhesion due to decreased expression of the fibronectin adhesin
      was compared with its isogenic parental strain. A significant reduction in
      adhesion of the fibronectin adhesin-defective mutant compared with the parental
      strain occurred on both the subcutaneously implanted and bone-implanted metallic
      plates. The results of this specific biological assay suggest that fibronectin is
      present on bone-implanted metallic devices and promotes attachment of S. aureus
      to their surfaces. This novel experimental model should help, to characterize
      several parameters of bacterial adhesion to metallic orthopaedic devices and to
      develop novel anti-adhesive strategies for preventing such infections.

PMID- 8982135
TI  - Bone growth after osteotomy and internal fixation in young rabbits.
AB  - The factors leading to overgrowth following fixation of long-bone fractures in
      children have never been clearly understood. The amount of trauma and the type of
      fixation may play a role. A rabbit model was used to investigate the influence of
      a femoral osteotomy and plate fixation on subsequent growth. Unilateral midshaft
      femoral osteotomy was performed in 6-week-old rabbits, and the bone was fixed
      internally with a plate and screws. End-to-end reduction was performed either at
      full length or with a segment removed. Bone length measurements at the end of
      growth revealed no significant difference in growth between the control femur and
      the femur that had undergone osteotomy and plate fixation. Shortened plated
      femora also showed no tendency to grow longer or faster than full-length fixed
      femora or controls. Interestingly, in the ipsilateral tibia a small but
      statistically significant length increase, equivalent to about 2% increase in
      additional growth, was observed, whereas technetium-99 methylene diphosphonate
      uptake was reduced in the tibial physes. In the context of the rabbit
      experimental model chosen, these results suggest that significant femoral over
      growth does not occur following femoral osteotomy and plate fixation.

PMID- 8982136
TI  - Differential growth by growth plates as a function of multiple parameters of
      chondrocytic kinetics.
AB  - Differential elongation of growth plates is the process by which growth-plate
      chondrocytes translate the same sequence of gene regulation into the appropriate
      timing pattern for a given rate of elongation. While some of the parameters
      associated with differential growth are known, the purpose of this study was to
      test the hypothesis that eight independent variables are involved. We tested this
      hypothesis by considering four different growth plates in 28-day-old Long-Evans
      rats. Temporal parameters were provided by means of oxytetracycline and
      bromodeoxyuridine labeling techniques. Stereological parameters were measured
      with standard techniques. For all four growth plates, the calculated number of
      new chondrocytes produced per day approximated the number of chondrocytes lost
      per day at the chondro-osseous junction. This suggests that the proposed
      equations and associated variables represent a comprehensive set of variables
      defining differential growth. In absolute numbers, the proximal tibial growth
      plate produced about four times as many chondrocytes per day as the proximal
      radial growth plate (16,400 compared with 3,700). In the proximal tibia, 9% of
      growth is contributed by cellular division; 32%, by matrix synthesis throughout
      the growth plate; and 59%, by chondrocytic enlargement during hypertrophy. In the
      more slowly elongating growth plates, the relative contribution to elongation
      from cellular enlargement decreases from 59 to 44%, with a relative increase in
      contribution from matrix synthesis ranging from 32% in the proximal tibia 49% in
      the proximal radius. This study suggests that differential growth is best
      depicted as a complex interplay among cellular division, matrix synthesis, and
      cellular enlargement during hypertrophy. Differential growth is best explained by
      considering a set of eight independent variables, seven of which vary from growth
      plate to growth plate. Thus, this study confirms the importance of cellular
      hypertrophy during elongation and adds to our understanding of the importance of
      locally mediated regulatory systems controlling growth-plate activity.

PMID- 8982137
TI  - Recombinant human bone morphogenetic protein-2 maintains the articular
      chondrocyte phenotype in long-term culture.
AB  - Bone morphogenetic proteins have been shown to increase matrix synthesis by
      articular chondrocytes in short-term cultures. Members of this family of proteins
      have also been shown to induce endochondral ossification in vivo. The present
      study was performed to determine if the addition of human recombinant bone
      morphogenetic protein-2 to a long-term monolayer articular chondrocyte cell
      culture system affected the ability of the chondrocytes to divide in vitro,
      whether the cytokine altered expression of the articular chondrocyte phenotype
      and synthesis of matrix proteoglycans, and whether the cytokine was capable of
      inducing differentiation to a hypertrophic chondrocyte. Human recombinant bone
      morphogenetic protein-2 did not alter cell proliferation. It caused 3.5-6.2 times
      more proteoglycan synthesis by articular chondrocytes during each of the time
      points tested after 4 days in culture. Total proteoglycan accumulation in the
      extracellular matrix after 28 days in culture was 6.7 times as great in the
      treated cultures as in the control. Treatment with human recombinant bone
      morphogenetic protein-2 maintained the articular chondrocyte phenotype of cells
      in culture as demonstrated by Northern blot analysis: the expression of type-I
      collagen genes was increased and that of type-II collagen and aggrecan mRNA was
      lost in untreated chondrocyte cultures after 14-21 days in culture. In contrast,
      exposure to 100 ng/ml human recombinant bone morphogenetic protein-2 maintained
      expression of type-II collagen and increased expression of aggrecan compared with
      controls during the 28-day culture period. Northern blot analysis of the
      expression of type-X collagen and osteocalcin by chondrocytes treated with human
      recombinant bone morphogenetic protein-2 showed a lack of expression of these
      genes, indicating no alteration in phenotype. These experiments demonstrated the
      ability of human recombinant bone morphogenetic protein-2 to promote the
      articular chondrocyte phenotype and matrix synthesis in long-term culture.
      Characteristics of cell growth were not affected, and the cytokine did not induce
      differentiation to a hypertrophic chondrocyte.

PMID- 8982138
TI  - Increased degradation and altered tissue distribution of cartilage oligomeric
      matrix protein in human rheumatoid and osteoarthritic cartilage.
AB  - We investigated the degradation and tissue distribution of cartilage oligomeric
      matrix protein in normal, osteoarthritic, and rheumatoid arthritic articular
      cartilage of the human knee. Cartilage was subjected to sequential extractions
      with buffers containing neutral salt, with EDTA, and finally with guanidine/HCl
      and then was analyzed by Western blotting with a polyclonal antiserum to human
      cartilage oligomeric matrix protein. Western blots of the nine neutral salt
      extracts from normal cartilage revealed mostly intact pentameric molecules of
      cartilage oligomeric matrix protein, in contrast to the 13 osteoarthritic and
      five rheumatoid arthritic cartilage samples that demonstrated marked degradation
      of cartilage oligomeric matrix protein as noted by a predominance of reduction
      sensitive bands at approximately 150 kDa and nonreduction-sensitive bands in the
      67-94 kDa range. The EDTA and guanidine/HCl extracts from all groups were similar
      and showed mostly intact molecules of cartilage oligomeric matrix protein, with
      smaller amounts of degraded cartilage oligomeric matrix protein identical to
      those resolved by the Western blots of the neutral salt extracts. Western blots
      of matched pairs of synovial fluid and cartilage extracts demonstrated cartilage
      oligomeric matrix protein fragments of the same molecular mass. Competitive
      enzyme-linked immunosorbent assay revealed significantly less cartilage
      oligomeric matrix protein in rheumatoid articular cartilage than in either normal
      or osteoarthritic cartilage. In contrast to normal cartilage, where cartilage
      oligomeric matrix protein was predominantly localized to the interterritorial
      matrix throughout all zones of the matrix, with increased staining in the deeper
      cartilaginous zones, the most intense staining in osteoarthritic cartilage was in
      the superficial zones of fibrillated cartilage, with little to no immunostaining
      in the midzones and relatively poor staining in the deeper cartilaginous zones.
      This distribution was the inverse of that for proteoglycans, as demonstrated by
      toluidine blue staining, where proteoglycans were depleted primarily from the
      superficial fibrillated cartilage. In mild to moderately affected rheumatoid
      cartilage, the tissue distribution of cartilage oligomeric matrix protein was
      similar to the distribution of proteoglycans, with relatively uniform staining of
      the interterritorial and territorial matrics. In more severely affected
      rheumatoid cartilage, the superficial zones demonstrated punctate immunostaining
      for cartilage oligomeric matrix protein in the interterritorial and territorial
      matrics, and staining was restricted to the territorial matrix in the deep
      cartilaginous zones. It is evident from this study that (a) noncollagenous
      proteins such as cartilage oligomeric matrix protein are greatly affected in
      arthritis, (b) degradation fragments released from the matrix into the synovial
      fluid reflect the processes occurring within the matrix, and (c) different zones
      of the articular cartilage are susceptible to degradation of cartilage oligomeric
      matrix protein in the different disease processes.

PMID- 8982140
TI  - Method for assessment of vascular reactivity in bone: in vitro studies on
      resistance arteries isolated from porcine cancellous bone.
AB  - Knowledge about vascular regulation in bone is central to the understanding of
      both normal and pathological bone physiology. This article describes a new method
      for direct assessment of the reactivity of bone blood vessels. Resistance
      arteries (diameter approximately 250 microns) were isolated from epiphyseal
      cancellous bone (porcine femoral condyle). Arterial segments (2 mm long) were
      mounted as ring preparations on a myograph, and isometric force development was
      measured continuously. Fifty-nine vessels from 31 pigs were investigated. The
      active force development was maximal at 0.9 x L100 in nine of 12 investigated
      arteries (L100 corresponds to the circumference the vessel would have if relaxed
      and exposed to a luminal pressure of 100 mm Hg [13.3 kPa]). In all subsequent
      experiments, the vessels were stretched to 0.9 x L100. Noradrenaline (2 x 10(-8)
      to 10(-5) M) induced a concentration-dependent vasoconstriction; mean maximal
      tension development was 3.69 N/m. This force development would enable the
      arteries to contract against a pressure of more than 22 kPa (165 mm Hg),
      indicating preserved function of the media smooth muscle. Response to
      acetylcholine (10(-7) to 10(-5) M) was observed in only two of 12 arteries.
      Bradykinin (10(-11) to 10(-6) M) induced a concentration-dependent and
      reproducible relaxation in all vessels; the relaxation was endothelium-dependent,
      since no effect of bradykinin was detected after mechanical removal of the
      endothelium. Sodium nitroprusside (10(-4) M) induced a reproducible and
      endothelium-independent vasorelaxation. The results demonstrate preserved
      function of both smooth muscle and endothelium in this preparation. The model
      allows pharmacological investigations of bone arteries under well defined
      conditions and enables studies on focal bone lesions and human bone tissue.

PMID- 8982139
TI  - Effect of human adrenomedullin on a canine tibial perfusion model in the absence
      of vascular endothelium.
AB  - The effect of human adrenomedullin was investigated using an ex vivo perfused
      canine tibial model in the absence of vascular endothelium. Adrenomedullin is a
      novel peptide with known vasodilator properties. In this model, a 0.1 ml bolus
      injection of 10(-5) M of either acetylcholine or adrenomedullin decreased
      vascular resistance in tibial preparations precontracted with prostaglandin F2
      alpha by 88.3 +/- 3.0% and 92.8 +/- 2.8%, respectively, in the presence of
      vascular endothelium. Conversely, a 0.1 ml bolus injection of 10(-5) M
      acetylcholine produced a constrictor response after removal of vascular
      endothelium. A 0.1 ml bolus injection of 10(-5) M adrenomedullin decreased the
      baseline perfusion pressure in a dose-dependent manner for a duration of 20
      minutes and also attenuated the pressor response to exogenous norepinephrine
      injection for at least 10 minutes compared with the control study (p < 0.05) in
      the absence of vascular endothelium. These data suggest that human adrenomedullin
      relaxes blood vessels in bone by a direct action on vascular smooth-muscle cells.
      In addition, the attenuation effect of human adrenomedullin on pressor responses
      to exogenous norepinephrine injection is independent of vascular endothelium.

PMID- 8982141
TI  - Osteocyte density and histomorphometric parameters in cancellous bone of the
      proximal femur in five mammalian species.
AB  - The species-specific relationships between trabecular morphology and osteocyte
      density were investigated in the femoral heads of 30 adult animals of five
      mammalian species (rat, rabbit, Rhesus monkey, pig, and cow). Our hypothesis is
      that osteocytes are mechanosensory cells and are involved in the regulation of
      bone remodeling. According to the predictions from a simulation model, this
      hypothesis implies that the influencing distance of osteocytes, together with the
      magnitude of the mechanical loads, determines the thickness of trabeculae and
      that the number of osteocytes primarily affects the rate of bone remodeling. The
      number of osteocytes per bone volume ranged from 93,200 mm-3 in rat to 31,900 mm
      3 in bovine cancellous bone. Osteocyte density was inversely related to the size
      of the species. Since basal metabolic output is related to body mass, we
      speculate that osteocyte density may be related to metabolic rates. Trabecular
      thickness was larger in the cow than in the other species, but the range of
      variation between species was relatively small. This agrees with the hypothesis
      that trabecular thickness is limited by the domain that can be regulated by an
      osteocyte and that this domain is of similar size regardless of the species. Only
      in the rat was trabecular thickness considerably smaller than in the other
      species. This is probably due to the presence of the cartilaginous growth plate
      in the femoral head of the rat. The relationships with species are different for
      osteocyte density than for morphometric parameters. Hence, our data support our
      hypothesis that osteocyte density is not directly associated with the macroscopic
      trabecular architecture.

PMID- 8982142
TI  - Effects of medial and lateral displacement calcaneal osteotomies on tibiotalar
      joint contact stresses.
AB  - Translational calcaneal osteotomies are used clinically to realign the mechanical
      axis of the lower limb. In this study, the effects of medial and lateral
      displacements of the posteroinferior fragment on tibiotalar joint contact
      mechanics were assessed using pressure-sensitive film. Eight osteotomized fresh
      frozen cadaver specimens were loaded in each of three testing positions: neutral
      position (no shift), 1 cm of lateral displacement of the inferior fragment with
      respect to the superior fragment, and 1 cm of medial displacement of the inferior
      fragment. For an applied load of 1,330 N, two times body weight, a 1 cm lateral
      displacement shifted the center of pressure an average of 1.06 mm laterally,
      whereas a 1 cm medial displacement shifted the center of pressure an average of
      1.58 mm medially. While global contact parameters (contact area, spatial mean
      contact stress, and peak local contact stress) were not appreciably altered by
      osteotomy, regional contact parameters changed in a reproducible and
      statistically significant manner. Among four nominally equal-sized,
      parasagittally bounded cartilage zones, lateral displacements consistently
      unloaded the most medial zone and increased loading of the most lateral zone;
      medial calcaneal displacements had the converse effect. These cadaver results
      suggest that translational calcaneal osteotomies may be used clinically to
      partially offload focal areas of cartilage along the medial and lateral borders
      of the tibiotalar joint.

PMID- 8982143
TI  - Kinematics of the glenohumeral joint: influences of muscle forces, ligamentous
      constraints, and articular geometry.
AB  - Despite recent interest in the study of shoulder kinematics, there is
      considerable controversy in the literature regarding translations at the
      glenohumeral joint. The purpose of this study was to investigate the key factors
      that control shoulder motions, thus leading to a better understanding of joint
      function. Translation and rotation patterns were studied in fresh-frozen
      glenohumeral joints of human cadavers with a six-degrees-of-freedom magnetic
      tracking device. Shoulders were positioned from maximal internal to external
      rotation at several arm positions (various elevations and planes of motion). In
      order to determine the effect of muscle forces, joints were positioned both
      actively and passively. Additionally, articular surface geometry and ligament
      origin-insertion wrap lengths were measured to assess their influences on joint
      kinematics. When joints were positioned passively, large translations were
      observed at the extremes of motion. With active positioning, muscle forces tended
      to limit humeral head translations, principally by restricting rotational ranges
      of motion. However, when data from the passive model were reanalyzed by
      considering only the rotational ranges of motion seen actively, no significant
      differences in translation were found between the two models. Joint conformity
      was found to have a significant influence on translations during active
      positioning but not during passive positioning. Glenohumeral ligament wrap
      lengths, however, correlated with translations when joints were positioned
      passively but not when positioned actively. Findings from this study emphasize
      the importance of muscle forces in keeping the humeral head centered in the
      glenoid. Although large translations are possible, they can be achieved only with
      increases in rotational ranges of motion associated with the removal of muscle
      force. Additionally, joint conformity appears to play a role in controlling
      translations during active motions, whereas capsular constraints become more
      important during passive motions.

PMID- 8982144
TI  - Genetic analysis of structural elastic fiber and collagen genes in familial
      adolescent idiopathic scoliosis.
AB  - Adolescent idiopathic scoliosis is a genetic disorder of unknown etiology.
      Scoliosis is a clinical feature of inherited connective-tissue disorders
      including Marfan syndrome. Mutations within the gene of FBN1 (fibrillin 15), a
      component of the extracellular matrix, are now linked to Marfan syndrome and
      similar clinical phenotypes. This study investigated the potential association of
      structural genes encoding for extracellular matrix components of FBN1, elastin,
      and one of the polypeptides of type-I collagen (COL1A2) with familial adolescent
      idiopathic scoliosis. Eleven pedigrees, including 96 individuals, were identified
      in which adolescent idiopathic scoliosis segregated in an apparent autosomal
      dominant pattern. Fifty-two individuals were determined to be affected with
      scoliosis. Genomic DNA was analyzed by genetic linkage utilizing four intragenic
      markers for the structural genes of FBN1, elastin, and COL1A2. Collectively, our
      results exclude the structural genes of FBN1, elastin, and COL1A2 as candidate
      genes within these families. However, when viewed individually, specific markers
      cannot be excluded within all of the families. This information complements
      previously reported data that fibrillin production and matrix incorporation from
      scoliotic fibroblasts in vitro are normal in more than 80% of patients studied.

PMID- 8982145
TI  - Technique for generating submicrometer ultra high molecular weight polyethylene
      particles.
AB  - Ultra high molecular weight polyethylene wear debris is believed to have a major
      role in aseptic loosening of prosthetic joints. In order to study the cellular
      and host response to this and other such particulate debris, a source of fine
      ultra high molecular weight polyethylene debris is needed. We have described a
      technique to fracture the GUR 4150 primary ultra high molecular weight
      polyethylene grain, which reproducibly generated particles less than 1 micron in
      size. Furthermore, the particle morphology was similar to that of ultra high
      molecular weight polyethylene particles generated in vivo and retrieved from
      interfacial tissues. The fabricated polyethylene particles ranged from 0.1 to 33
      microns in diameter, with a mean of 2.3 +/- 0.2 micron. Sixty percent of the
      particles were smaller than 1 micron and 90% were smaller than 7 microns. Using
      filtration and sedimentation, it is possible to acquire finer particle fractions.
      These particles are currently being used for biological response studies.

PMID- 8982146
TI  - Human anterior and posterior cervical longitudinal ligaments possess similar
      tensile properties.
AB  - One hundred bone-ligament-bone complexes were isolated from the cervical spines
      of 20 fresh-frozen human cadavers and mechanically tested in uniaxial tension.
      Load-elongation curves representing the structural properties of the complex were
      obtained, and stiffness, ultimate load, energy at failure, and elongation were
      determined from the curves. Stress-strain curves representing the mechanical
      properties of the ligament substance were also obtained, and elastic modulus was
      determined from these curves. Comparisons were made between anterior and
      posterior longitudinal ligaments and among cervical levels. The cross-sectional
      area of the anterior ligament was smaller at the C2-C3 level than at subaxial
      levels. There was a trend toward less stiffness but more energy at failure and
      greater elastic modulus for the anterior compared with the posterior ligaments at
      subaxial levels, although the differences were not statistically significant (p >
      0.05).

PMID- 8982147
TI  - X-linked agammaglobulinemia. A clinical and molecular analysis.
AB  - X-linked agammaglobulinemia (XLA), characterized by a profound deficiency of B
      lymphocytes due to an arrest in B lymphocyte development, is caused by mutations
      in the gene encoding Btk (Bruton tyrosine kinase). The BTK gene has been cloned
      and the genomic organization determined. BTK codes for 19 exons and is expressed
      in all hematopoietic cell lineages but is selectively down-regulated in T
      lymphocytes and plasma cells. The different Btk domains include PH, TH, SH3, SH2,
      and the kinase (SH1) domains. Btk, a cytoplasmic protein tyrosine kinase, is
      involved in cell signaling, although the precise pathway remains elusive.
      Mutation analysis has been performed in 236 families representing 282 patients.
      Mutations are scattered throughout the gene and consist of missense, nonsense,
      and splice site mutations as well as deletions and insertions. The major
      consequence of nonfunctional Btk appears to be a delay or block of the
      development of pro-B cells to pre-B cells and then to mature lymphocytes. Because
      IgG is actively transported across the placenta, affected newborns have normal
      levels of serum IgG at birth followed by gradually decreasing IgG levels and
      development of hypogammaglobulinemia and increased susceptibility to infections.
      Bacterial infections are the most common clinical manifestation. Resistance to
      viral infection is intact, except for an unusual susceptibility to infections
      with enteroviruses that may result in vaccine-related paralytic poliomyelitis or
      a dermatomyositis-meningoencephalitis syndrome. The diagnosis of XLA is based on
      the presence of lymphoid hypoplasia, markedly reduced serum levels of all 3 major
      classes of immunoglobulins, failure to make antibody to antigenic stimulation,
      and almost complete absence of B lymphocytes in the peripheral blood. Carrier
      detection and prenatal diagnosis are possible. The prophylactic infusion of high
      dose intravenous immunoglobulin (IVIG) and the use of antibiotics have markedly
      improved the long-term prognosis of patients with XLA.

PMID- 8982148
TI  - Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive
      "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia.
AB  - Painful crises in patients with sickle cell anemia are caused by vaso-occlusion
      and infarction. Occlusion of blood vessels depends on (at least) their diameter,
      the deformability of red cells, and the adhesion of blood cells to endothelium.
      Deoxygenated sickle cells are rigid because they contain linear polymers of
      hemoglobin S (Hb S); polymerization is highly concentration dependent, and
      dilution of Hb S by a nonsickling hemoglobin such as fetal hemoglobin (Hb F)
      would be expected to lead ultimately to a decrease in the frequency of painful
      crises. It might also be expected to decrease the severity of anemia, although
      the pathogenesis of anemia in sickle cell anemia (SS disease) is not clearly
      understood. Reversion to production of fetal rather than adult hemoglobin became
      practical with the discovery that HU was an orally effective and relatively safe
      "switching agent." Preliminary dose-ranging studies led to a double-blind
      randomized controlled clinical trial, the Multicenter Study of Hydroxyurea in
      Sickle Cell Anemia (MSH), designed to test whether patients treated with HU would
      have fewer crises than patients treated with placebo. The MSH was not designed to
      assess the mechanism(s) by which a beneficial effect might be achieved, but it
      was hoped that observations made during the study might illuminate that question.
      The 2 MSH treatment groups were similar to each other and were representative of
      African-American patients with relatively severe disease. The trial was closed
      earlier than expected, after demonstration that median crisis rate was reduced by
      almost 50% (2.5 versus 4.5 crises per year) in patients assigned to HU therapy.
      Hospitalizations, episodes of chest syndrome, and numbers of transfusions were
      also lower in patients treated with HU. Eight patients died during the trial, and
      treatment was stopped in 53. There were no instances of alarming toxicity.
      Patients varied widely in their maximum tolerated doses, but it was not clear
      that all were taking their prescribed treatments. When crisis frequency was
      compared with various clinical and laboratory measurements, pretreatment crisis
      rate and treatment with HU were clearly related to crisis rate during treatment.
      Pretreatment laboratory measurements were not associated with crisis rates during
      the study in either treatment group. It was not clear that clinical improvement
      was associated with an increase in Hb F. Crisis rates of the 2 treatment groups
      became different within 3 months. Mean corpuscular volumes (MCVs) and the
      proportion of Hb F containing red cells (F cells) rose, and neutrophil and
      reticulocyte counts fell, within 7 weeks. When patients were compared on the
      basis of 2-year crisis rates, those with lower crisis rates had higher F-cell
      counts and MCVs and lower neutrophil counts. Neutrophil, monocyte, reticulocyte,
      and platelet counts were directly associated, and F cells and MCV were inversely
      associated, with crisis rates in 3-month periods. In multivariable analyses,
      there was strong evidence of independent association of lower neutrophil counts
      with lower crisis rates. F-cell counts were associated with crisis rate only in
      the first 3 months of treatment; MCV showed an association over longer periods of
      time. Overall, the evidence that decreased neutrophil counts played a role in
      reducing crisis rates was strong. Increased F cells or MCV and evidence of
      cytoreduction by HU were also associated with decreased crisis rates, but no
      definitive statement can be made regarding the mechanism of action of HU because
      the study was not designed to address that question. Future studies should be
      designed to explore the mechanism of action of HU, to identify the optimal dosage
      regimen, and to study the effect of HU when combined with other antisickling
      agents.

PMID- 8982149
TI  - Hepatomegaly and abnormal liver tests due to glycogenosis in adults with
      diabetes.
AB  - In adults with diabetes mellitus, hepatomegaly and abnormalities of liver enzymes
      occur as a consequence of hepatocellular glycogen accumulation, as has been well
      described in children. During periods of hyperglycemia glucose freely enters the
      hepatocytes driving glycogen synthesis, which is augmented further by
      administration of insulin to supraphysiologic levels. The accumulation of
      excessive amounts of glycogen in the hepatocytes is a function of intermittent
      episodes of hyperglycemia and hypoglycemia and the use of excessive insulin.
      Hepatic glycogenosis occurs in patients with poorly controlled insulin-dependent
      type I or type II diabetes. The clinical manifestations of this phenomenon may
      include abdominal pain and obstructive symptoms such as early satiety, nausea,
      and vomiting. Ascites has rarely been reported. The typical biochemical findings
      are mildly to moderately elevated aminotransferases, with or without mild
      elevations of alkaline phosphatase. Liver synthetic function is usually normal.
      All these abnormalities, including the hepatomegaly, are readily reversible with
      sustained euglycemic control. The other major cause of hepatomegaly in patients
      with diabetes is steatosis. This is a function of the body habitus and state of
      insulin resistance rather than glycemic control. However, the distinction between
      steatosis and glycogenosis is important: whereas steatosis may progress to
      fibrosis and cirrhosis, glycogenosis does not, but reflects the need for better
      diabetic control. Glycogenosis and steatosis cannot be distinguished reliably on
      ultrasound examination. The histology, however, is definitive. In glycogenosis,
      as in primary glycogen storage diseases, there is excess glycogen in the
      cytoplasm, and often also in the nucleus, of hepatocytes. The hepatocytes
      throughout the lobule appear pale and swollen with clearly defined cell
      boundaries. Ultrastructural examination reveals cytoplasmic glycogen in clumps
      displacing organelles to the periphery of the cell, and there is little if any
      steatosis. We have shown that hepatomegaly due to glycogenosis in adults with
      diabetes is similar in all respects to the condition seen in children. As in
      children, liver enzyme abnormalities are unreliable in predicting the presence or
      the extent of glycogenosis. Hepatic glycogenosis can occur at any age, and
      therefore should be included in the differential diagnosis of hepatomegaly in all
      insulin-requiring diabetics.

PMID- 8982150
TI  - Acute eosinophilic pneumonia. A summary of 15 cases and review of the literature.
AB  - Idiopathic acute eosinophilic pneumonia (AEP) is an acute febrile illness that
      may be mistaken for an infectious pneumonia. Patients are often young and
      otherwise healthy. Clues to considering this disorder in a differential diagnosis
      include the acuity and severity of the clinical presentation and an initial chest
      X-ray with diffuse infiltrates, often interstitial, and the presence of Kerley B
      lines and/or evidence of pleural fluid. The diagnosis can be made through
      examination of bronchoalveolar lavage fluid in most cases, with careful exclusion
      of other similar eosinophilic lung disease. Although it can lead to life
      threatening respiratory failure, AEP is easily treatable with corticosteroids.
      This disease has not been reported to recur in any patients to this point.

PMID- 8982151
TI  - Axons turn as netrins find their receptor.

PMID- 8982152
TI  - Endocytosis at nerve terminals: timing is everything.

PMID- 8982153
TI  - Molecular biology of axon guidance.

PMID- 8982154
TI  - Exocytosis: a molecular and physiological perspective.

PMID- 8982155
TI  - Neurotrophin regulation of cortical dendritic growth requires activity.
AB  - Neurotrophins have been proposed to mediate several forms of activity-dependent
      competition in the central nervous system. A key element of such hypotheses is
      that neurotrophins act preferentially on active neurons; however, little direct
      evidence supports this postulate. We therefore examined, in ferret cortical brain
      slices, the interactions between activity and neurotrophins in regulating
      dendritic growth of layer 4 pyramidal neurons. Inhibition of spontaneous
      electrical activity, synaptic transmission, or L-type calcium channels each
      prevented the otherwise dramatic increase in dendritic arborizations elicited by
      brain-derived neurotrophic factor. In developing cortex, this requirement for
      conjoint neurotrophin signaling and activity provides a mechanism for selectively
      enhancing the growth and connectivity of active neurons.

PMID- 8982157
TI  - Guidance of circumferentially growing axons by netrin-dependent and -independent
      floor plate chemotropism in the vertebrate brain.
AB  - Netrin-1, a diffusible signal secreted by floor plate cells at the ventral
      midline of the vertebrate CNS, can attract ventrally migrating axons and repel a
      subset of dorsally migrating axons in the spinal cord and rostral hindbrain in
      vitro. Whether netrin-1 can act as a global cue to guide all circumferentially
      migrating axons is, however, unknown. Here, we show that netrin-1 can attract
      alar plate axons that cross the floor plate along its entire rostrocaudal axis.
      Dorsally directed axons forming the posterior commissure are, however, repelled
      by the floor plate by a netrin-independent mechanism. These results suggest that
      netrin-1 functions as a global guidance cue for attraction to the midline.
      Moreover, floor plate-mediated chemorepulsion may also operate generally to
      direct dorsal migrations, but its molecular basis may involve both netrin
      dependent and -independent mechanisms.

PMID- 8982158
TI  - Inhibitors and promoters of thalamic neuron adhesion and outgrowth in embryonic
      neocortex: functional association with chondroitin sulfate.
AB  - When embryonic thalamic neurons are plated onto living slices of mouse forebrain,
      cell attachment and neurite outgrowth on different layers of the developing
      cerebral cortex vary dramatically, in ways that correlate with the timing and
      pattern of thalamocortical innervation. These layer-specific differences can be
      eliminated from embryonic day 16 slices by enzymatic removal of chondroitin
      sulfate (CS). The cortical plate (a zone avoided by thalamic axons in vivo)
      possesses inhibitory activity (anti-adhesive, neurite repelling) and the
      intermediate zone and subplate (in which thalamic axons normally grow) possess
      stimulatory activity (adhesive, neurite promoting), both of which are
      chondroitinase sensitive. These opposing activities appear not to reflect the
      presence of different CS proteoglycans (CSPGs) in different zones, but rather the
      presence of differentially localized CS-binding molecules, which can be competed
      away by soluble CS. This model reconciles conflicting reports on the actions of
      CSPGs in neural development, and suggests a role for CSPGs in the organization of
      matrix-bound cues in the brain.

PMID- 8982156
TI  - Lack of neurotrophin-3 results in death of spinal sensory neurons and premature
      differentiation of their precursors.
AB  - To understand mechanisms resulting in the absence of two-thirds of spinal sensory
      neurons in mice lacking NT-3, we have compared dorsal root ganglia development in
      normal and mutant embryos. The reduction in neurons, achieved by E13, results
      from several deficits: first, elevated neuronal apoptosis significantly reduces
      neuronal numbers; second, elevated neurogenesis between E11 and E12, without
      changes in rates of precursor proliferation or apoptosis, depletes the precursor
      pool; consequently, the reduced precursor pool prevents increases in neuronal
      numbers between E12 and E13, when most neurons are born in normal animals.
      Although deficits occur before final target innervation, we show that NT-3 is
      expressed at all stages in regions accessible to these neurons or their axons and
      is only restricted to final targets after innervation.

PMID- 8982159
TI  - Identification of a novel Drosophila opsin reveals specific patterning of the R7
      and R8 photoreceptor cells.
AB  - The function of the compound eye is dependent upon a developmental program that
      specifies different cell fates and directs the expression of spectrally distinct
      opsins in different photoreceptor cells. Rh5 is a novel Drosophila opsin gene
      that encodes a biologically active visual pigment that is expressed in a subset
      of R8 photoreceptor cells. Rh5 expression in the R8 cell of an individual
      ommatidium is strictly coordinated with the expression of Rh3, in the overlying
      R7 cell. In sevenless mutant files, which lack R7 photoreceptor cells, the
      expression of the Rh5 protein in R8 cells is disrupted, providing evidence for a
      specific developmental signal between the R7 and R8 cells that is responsible for
      the paired expression of opsin genes.

PMID- 8982160
TI  - PDGF mediates a neuron-astrocyte interaction in the developing retina.
AB  - Astrocytes invade the developing retina from the optic nerve head, over the axons
      of retinal ganglion cells (RGCs). RGCs express the platelet-derived growth factor
      A-chain (PDGF-A) and retinal astrocytes the PDGF alpha-receptor (PDGFR alpha),
      suggesting that PDGF mediates a paracrine interaction between these cells. To
      test this, we inhibited PDGF signaling in the eye with a neutralizing anti-PDGFR
      alpha antibody or a soluble extracellular fragment of PDGFR alpha. These
      treatments inhibited development of the astrocyte network. We also generated
      transgenic mice that overexpress PDGF-A in RGCs. This resulted in
      hyperproliferation of astrocytes, which in turn induced excessive vasculogenesis.
      Thus, PDGF appears to be a link in the chain of cell-cell interactions
      responsible for matching numbers of neurons, astrocytes, and blood vessels during
      retinal development.

PMID- 8982161
TI  - Spatiotemporal dynamics of CREB phosphorylation: transient versus sustained
      phosphorylation in the developing striatum.
AB  - The cAMP response element-binding protein (CREB) is a plasticity-associated
      transcription factor that can potentially integrate cAMP and calcium signals at
      the gene activation level. We tested for convergent Ser-133 phosphorylation of
      CREB via dopamine D1/D5 receptors and L-type calcium channels in organotypic
      cultures of neonatal striatum. We found such convergence only transiently.
      Sustained CREB phosphorylation by D1/D5 receptor and L-type channel agonists was
      targeted to opposite (striosome and matrix) cellular phenotypes. Subsequent
      expression of the CRE-containing gene, c-fos, matched the divergent patterns of
      sustained CREB phosphorylation, and both divergent patterns could be switched by
      inhibition of phosphatases, including calcineurin. Control of the duration of
      CREB phosphorylation may be a critical regulator of CRE-mediated gene expression
      by dopamine and calcium.

PMID- 8982162
TI  - Imaging the functional organization of zebrafish hindbrain segments during escape
      behaviors.
AB  - Although vertebrate hindbrains are segmented structures, the functional
      significance of the segmentation is unknown. In zebrafish, the hindbrain segments
      contain serially repeated classes of individually identifiable neurons. We took
      advantage of the transparency of larval zebrafish and used confocal calcium
      imaging in the intact fish to study the activity of one set of individually
      identified, serially homologous reticulospinal cells (the Mauthner cell, MID2cm,
      and MID3cm) during behavior. Behavioral studies predicted that differential
      activity in this set of serially homologous neurons might serve to control the
      directionality of the escape behavior that fish use to avoid predators. We found
      that the serially homologous cells are indeed activated during escapes and that
      the combination of cells activated depends upon the location of the sensory
      stimulus used to elicit the escape. The patterns of activation we observed were
      exactly those predicted by behavioral studies. The data suggest that duplication
      of ancestral hindbrain segments, and subsequent functional diversification,
      resulted in sets of related neurons whose activity patterns create behavioral
      variability.

PMID- 8982163
TI  - Hepatocyte growth factor/scatter factor is an axonal chemoattractant and a
      neurotrophic factor for spinal motor neurons.
AB  - In the embryonic nervous system, developing axons can be guided to their targets
      by diffusible factors secreted by their intermediate and final cellular targets.
      To date only one family of chemoattractants for developing axons has been
      identified. Grafting and ablation experiments in fish, amphibians, and birds have
      suggested that spinal motor axons are guided to their targets in the limb in part
      by a succession of chemoattractants made by the sclerotome and by the limb
      mesenchyme, two intermediate targets that these axons encounter en route to their
      target muscles. Here we identify the limb mesenchyme-derived chemoattractant as
      hepatocyte growth factor/scatter factor (HGF/SF), a diffusible ligand for the c
      Met receptor tyrosine kinase, and we also implicate HGF/SF at later stages as a
      muscle-derived survival factor for motoneurons. These results indicate that, in
      addition to functioning as a mitogen, a motogen, and a morphogen in nonneural
      systems, HGF/SF can function as a guidance and survival factor in the developing
      nervous system.

PMID- 8982164
TI  - Molecular characterization of the dendritic growth cone: regulated mRNA transport
      and local protein synthesis.
AB  - The molecular mechanisms that regulate growth cone guidance of dendrite outgrowth
      remain to be elucidated. We hypothesized that mRNA localization in dendritic
      growth cones and their local protein synthesis may be important for growth cone
      functioning. The appearance of 23 of 31 growth cone mRNAs was developmentally
      regulated. Also, alteration of growth cone morphology affected the relative
      levels of three mRNAs. Finally, using single dendrite transfection, it was shown
      that local protein synthesis occurs in dendrites and growth cones. A
      heterogeneous population of mRNAs exists in dendritic growth cones of cultured
      hippocampal neurons whose relative abundances are developmentally regulated and
      can vary with changes in growth cone physiology. The demonstration of protein
      synthesis in growth cones suggests that translation of the localized mRNAs may
      contribute to regulation of growth cone motility and dendrite outgrowth.

PMID- 8982165
TI  - Cytoskeletal plasticity in cells expressing neuronal microtubule-associated
      proteins.
AB  - MAP2 and tau are the two most prominent neuron-specific microtubule-associated
      proteins. They have been implicated in the stabilization of microtubules and
      consequently of neurite morphology. To investigate their influence on microtubule
      dynamics, we have tagged both proteins with green fluorescent protein and
      expressed them in non-neuronal cells. Time-lapse recordings of living cells
      showed that MAP2 and tau did not significantly affect the rates of microtubule
      growth and shrinkage. Longer recordings revealed the growth and disappearance of
      MAP-induced microtubule bundles coinciding with changes in cell shape. This
      supports the idea that microtubule dynamics are influenced by the cortical
      cytoskeleton. The dynamics-preserving stabilization of microtubules by MAP2 and
      tau thus provides a molecular basis for the morphological plasticity reported to
      exist in established neurites.

PMID- 8982166
TI  - Regulation of the phosphorylation state and microtubule-binding activity of Tau
      by protein phosphatase 2A.
AB  - Recently, we reported that a pool of protein phosphatase 2A (PP2A) is associated
      with microtubules. Here, we demonstrate that specific isoforms of PP2A bind and
      dephosphorylate the neuronal microtubule-associated protein tau. Coexpression of
      tau and SV40 small t, a specific inhibitor of PP2A, in CV-1, NIH 3T3, or NT2
      cells induced the phosphorylation of tau at multiple sites, including Ser-199,
      Ser-202, Thr-205, Ser-396, and Ser-404. Immunofluorescent and biochemical
      analyses revealed that hyperphosphorylation correlated with dissociation of tau
      from microtubules and a loss of tau-induced microtubule stabilization. Taken
      together, these results support the hypothesis that PP2A controls the
      phosphorylation state of tau in vivo.

PMID- 8982167
TI  - The mammalian brain rsec6/8 complex.
AB  - rsec6 and rsec8 are two components of a 17S complex in mammalian brain that is
      homologous to the yeast 834 kDa Sec6/8/15 complex which is essential for
      exocytosis. Purification and partial amino acid sequencing of the mammalian
      rsec6/8 complex reveals that it is composed of eight novel proteins with a
      combined molecular weight of 743 kDa. The complex is broadly expressed in brain
      and displays a plasma membrane localization in nerve terminals. Membrane
      associated rsec6/8 complex coimmunoprecipitates with syntaxin, a plasma membrane
      protein critical for neurotransmission. These data suggest a role for the
      mammalian rsec6/8 complex in neurotransmitter release via interactions with the
      core vesicle docking and fusion apparatus.

PMID- 8982168
TI  - Determinants of nicotinic receptor gating in natural and unnatural side chain
      structures at the M2 9' position.
AB  - A nonsense suppression method was employed to incorporate a total of four natural
      and six unnatural residues at the 9' position of the M2 region in the beta,
      gamma, and delta subunits of muscle nicotinic receptors. In 33 pairwise
      comparisons of functional properties as influenced by structural features
      including side chain length, branching, and substitution of oxygen for methylene
      carbons, it is concluded that increased polarity in the side chains at the 9'
      position consistently increases the sensitivity to acetylcholine. In addition,
      the stereochemistry of the side chain can have marked influences on the EC50,
      primarily because of changes in the single-channel open time. For the case of
      isoleucine versus allo-isoleucine in the delta subunit, these changes are
      themselves modified by mutations at the 9' position in other subunits. The data
      suggest an especially strong interaction between the beta and delta subunits in
      the pore region, leading in turn to a suggested arrangement of subunits within
      the pentamer.

PMID- 8982169
TI  - Synaptic currents generated by neuronal acetylcholine receptors sensitive to
      alpha-bungarotoxin.
AB  - Nicotinic acetylcholine receptors are widely distributed throughout the nervous
      system, but their functions remain largely unknown. One of the most abundant is a
      class of receptors that contains the alpha 7 gene product, has a high relative
      permeability to calcium, and binds alpha-bungarotoxin. Here, we report that
      receptors sensitive to alpha-bungarotoxin, though concentrated in perisynaptic
      clusters on neurons, can generate a large amount of the synaptic current.
      Residual currents through other nicotinic receptors are sufficient to elicit
      action potentials, but with slower rise times. This demonstrates a postsynaptic
      response for alpha-bungarotoxin-sensitive receptors on neurons and suggests that
      the functional domain of the postsynaptic membrane is broader than previously
      recognized.

PMID- 8982170
TI  - Ultrafast exocytosis elicited by calcium current in synaptic terminals of retinal
      bipolar neurons.
AB  - Using high resolution capacitance measurements, we have characterized an
      ultrafast component of transmitter release in ribbon-type synaptic terminals of
      retinal bipolar neurons. During depolarization, capacitance increases to a
      plateau of approximately 30 fF with a time constant of approximately 1.5 ms. When
      not limited by activation kinetics of calcium current, the small pool is depleted
      even faster, with a time constant of 0.5 ms. After the ultrafast pool is
      depleted, capacitance rises with a slower time constant of approximately 300 ms.
      EGTA (5 mM) depresses the slower capacitance rise but leaves the ultrafast phase
      intact. BAPTA (5 mM) depresses both components of exocytosis. With paired-pulse
      stimulation, the ultrafast pool recovers from depletion with a time constant of
      approximately 4 s. The ultrafast component may represent fusion of docked
      vesicles at the base of the synaptic ribbon, while the slower component
      represents more distal vesicles on the ribbon.

PMID- 8982171
TI  - Inner ear defects induced by null mutation of the isk gene.
AB  - The isk gene is expressed in many tissues. Pharmacological evidence from the
      inner ear suggests that isk mediates potassium secretion into the endolymph. To
      examine the consequences of IsK null mutation on inner ear function, and to
      produce a system useful for examining the role(s) IsK plays elsewhere, we have
      produced a mouse strain that carries a disrupted isk locus. Knockout mice exhibit
      classic shaker/waltzer behavior. Hair cells degenerate, but those of different
      inner ear organs degenerate at different times. Functionally, we show that in
      mice lacking isk, the strial marginal cells and the vestibular dark cells of the
      inner ear are unable to generate an equivalent short circuit current in vitro,
      indicating a lack of transepithelial potassium secretion.

PMID- 8982172
TI  - The Cochrane Collaboration: New Zealand gets involved.

PMID- 8982173
TI  - Nutrient intakes of Tongan and Tokelauan children living in New Zealand.
AB  - AIMS: To assess the adequacy of nutrient intakes of 10- to 13-year-old Tongan and
      Tokelauan children living in New Zealand and to compare these data with data from
      nonPacific Islands children of the same age. METHODS: A 24-hour diet record was
      used to assess the nutrient intakes of Tongan and Tokelauan school children (n =
      162), aged 10- to 13-years, living in Auckland and Wellington. Nutrient intakes
      using the same methodology were compared with those from a nationally
      representative sample of nonPacific Islands, Form 1 children and also with
      Australian recommended dietary intakes for children aged 12- to 15-years.
      RESULTS: Data were collected from 162 (68 boys and 94 girls) of 220 children
      eligible to participate in the study (74%). Mean energy intakes for both the
      Tongan (8855 kJ for boys, 8610 kJ for girls) and the Tokelauan (9872 kJ for boys,
      8826 kJ for girls) children were above the range of intake recommended by the
      World Health Organisation. The combined average energy intake of the two groups
      was higher than that of nonPacific Islands children for both boys and girls
      although not statistically significantly. Total fat intake was significantly
      higher (p < 0.05) for Tongan and Tokelauan boys, protein intake significantly
      higher for Tongan and Tokelauan boys (p < 0.01) and girls (p < 0.01), and
      carbohydrate intake significantly lower (p < 0.01) for Tongan and Tokelauan girls
      than for nonPacific Islands children. Compared with nonPacific Islands children
      micronutrient intakes were generally lower for Tongan and Tokelauan children with
      intakes of calcium, riboflavin, thiamin, niacin, folate and vitamin A being
      significantly lower for both sexes. Vitamin C was also significantly lower for
      girls (p < 0.05). Tongan and Tokelauan children obtain most of their nutrients
      from meat, bakery products, fast foods and dairy products. Fruit and vegetables
      were not significant contributors to nutrient intakes. CONCLUSIONS: Tongan and
      Tokelauan children living in New Zealand consume a diet that is larger in amount
      but lower in nutrient density compared to that of nonPacific Islands New Zealand
      children. Their relatively high dietary energy intakes allow them to meet the
      recommended intake requirements for most nutrients although if current intakes of
      fat and energy are maintained this may put them at risk of heart disease and
      other diseases later in life.

PMID- 8982174
TI  - The prescription of domicilary long-term oxygen therapy in Auckland.
AB  - AIMS: (a) To assess the mode of referral and the demographic and clinical
      characteristics of patients prescribed oxygen between 1 January and 31 December
      1994. (b) To assess whether international guidelines for prescribing oxygen were
      adhered to. (c) To assess the rate and pattern of prescription of oxygen in
      Auckland compared with other developed countries, and (d) based on these
      findings, to ascertain whether changes need to be made to our practise. METHOD:
      Notes of all patients referred to the oxygen service in 1994 were reviewed.
      RESULTS: The oxygen service received 304 referrals in 1994 and 196 (including 23
      infants), were commenced on long-term oxygen therapy. The primary diagnosis was
      chronic obstructive pulmonary disease (COPD) in 90 (52%), other chronic
      respiratory diseases 25 (14%) and terminal malignancy in 48(28%). Of the 173
      adult patients prescribed oxygen 79% of patients were referred as a result of
      hospital admission. Thirty three percent of chronic obstructive pulmonary disease
      patients died within 6 months of receiving domiciliary oxygen which is higher
      than any previously published report. Mortality rates were no different between
      patients with chronic obstructive pulmonary disease and other respiratory
      disorders. CONCLUSIONS: International guidelines for oxygen therapy were
      generally adhered to in Auckland though improvements could be made to ensure
      better quality information on referral and by use of blood gas analysis rather
      than oximetry. Fewer chronic obstructive pulmonary disease patients are receiving
      oxygen therapy in Auckland than expected and it is often prescribed late and as a
      result of hospital admission. Closer adherence to more recently published
      international guidelines and better targeting of patients with respiratory
      failure will impose a greater financial burden on the oxygen service, but may
      result in improved survival and reduced need of hospital admission. These
      findings have important resource implications, for oxygen services in New Zealand
      if they are to comply with International Guidelines for Domiciliary Oxygen
      Therapy.

PMID- 8982175
TI  - A comparison between colorectal surgical admissions in Maori and nonMaori.
AB  - AIMS: To compare Maori with nonMaori colorectal surgical admissions to a
      specialised colorectal unit in a teaching hospital. METHODS: All patients
      admitted to the colorectal service of the university department of surgery,
      Wellington, New Zealand between April 1975 and March 1990 have been entered into
      a computerised data base. Patients claiming to be Maori or of Maori descent were
      compared, in relation to colorectal diagnosis, type of admission and surgery and
      surgical complications, with those designated European or other. RESULTS: There
      were 90 Maori admissions (47 male, 43 female) and 1842 nonMaori admissions (1007
      male, 835 female). The urgency of admission was similar in both groups. There
      were no significant differences in admission rates for obstruction, perforation,
      bleeding, diverticular disease, or anorectal abscess but more Maori seemed to
      have problems with haemorrhoids and perineal condylomata acuminata. More nonMaori
      were admitted with colorectal cancer. The frequencies of most major operations
      were similar in the two groups studied, although haemorrhoidectomy was more
      common in the Maori. A higher proportion of nonMaori patients had a consultant
      surgeon as the primary operator. The overall complication rates, with the
      exception of urinary tract infections were similar in both groups. One Maori
      patient died and there were 31 nonMaori deaths. CONCLUSION: There was no evidence
      that Maori had either less access to the public hospital system or that surgical
      colorectal diseases were more neglected. In general hospital admission rates for
      colorectal diseases in Maori and nonMaori were remarkably similar.

PMID- 8982177
TI  - Screening for colorectal cancer: a survey of New Zealand general practitioners.
AB  - AIM: To determine the attitudes and reported behaviours of New Zealand general
      practitioners concerning colorectal cancer screening and diagnosis with special
      consideration of the use of faecal occult blood tests. METHOD: A postal survey of
      a random sample of 400 New Zealand general practitioners. RESULTS: The response
      rate to the survey was 63%. Most of the respondents did not support a screening
      programme for average risk patients but did support screening in high risk
      groups. General practitioners favoured a screening programme offered by
      themselves rather than a centrally organised screening programme. A majority of
      respondents agreed that there was a lack of clear guidelines and a need for
      education regarding screening for bowel cancer. CONCLUSION: Guidelines for
      colorectal cancer screening are required for New Zealand general practitioners.
      There appears to be a need for medical education concerning screening for
      colorectal cancer in particular and screening and prevention in general.

PMID- 8982176
TI  - Survey of Waikato medical practitioners concerning cardiac pacing.
AB  - AIM: To assess the knowledge of Waikato medical practitioners concerning cardiac
      pacing and its indications. METHOD: Anonymous postal questionnaire. The responses
      received were compared with those of four New Zealand experts on cardiac pacing.
      RESULTS: 404 questionnaires were administered of which 204 (50%) were returned,
      (16.3% physicians, 22.7% JRMO's 61% general practitioners). Virtually all had
      ready access to diagnostic facilities and were satisfied with the service
      offered. Physicians were more likely to have referred patients and to have had
      personal experience with pacing. Practical matters, such as costs and length of
      the procedure were reasonably well appreciated. The complexity of the procedure,
      however, was overestimated. Pacemaker function was poorly understood. All
      practitioner groups were less likely to refer for pacing compared with the
      experts, but were more likely to refer in the presence of recurrent symptoms,
      particularly if the patient was elderly. CONCLUSION: A conservative approach to
      referral for permanent pacing exists in the Waikato region and this is unrelated
      to access to diagnostic facilities or referral difficulties.

PMID- 8982178
TI  - Hearing aid use and benefit and uptake of aural rehabilitation services by New
      Zealand hearing aid wearers.
AB  - AIM: To provide the first extensive survey in New Zealand of hearing aid use and
      benefit and the accessibility of Hearing Association services. METHOD: A mail-out
      questionnaire was used to survey 197 Auckland adult hearing aid wearers regarding
      patterns of hearing aid use and benefit and the accessibility of Hearing
      Association aural rehabilitation services. RESULTS: Hearing aid benefit was
      moderate and was not related to age or hearing aid use variables. Knowledge and
      usage of local rehabilitation services was limited. Perceived functions of the
      Hearing Association included adult audiometry and counselling. Respondents wanted
      assistance with hearing aid management and assistive listening devices. Physical
      access, financial and time constraints were seen as barriers to using
      rehabilitative services. DISCUSSION: It appears that there is not a simple
      relationship between perceived benefit or satisfaction and the amount of time
      people wear their hearing aids. The low level of awareness and participation in
      Hearing Association services is consistent with the underutilisation of such
      services found previously.

PMID- 8982179
TI  - Thrombosis and protein S deficiency in HIV infection.

PMID- 8982180
TI  - An economic analysis of health care reform and its implications for plastic
      surgery.

PMID- 8982181
TI  - A comparison between parallel hairline incisions and perpendicular incisions when
      performing a face lift.
AB  - Our profession has not decided if it is better to incise parallel or
      perpendicular (at an angle) to hair follicles when performing a brow lift or a
      face lift. Thirty patients had one side incised parallel and the other side
      incised perpendicular to hair follicles. Neither the patients nor the examiners
      knew how each side was incised. By comparing the invisibility, the nonlinearity,
      the absence of hypopigmentation, and the abundance of hair into and in front of
      the scar, we obtained statistical proof that if we incised perpendicular to hair
      follicles (to preserve the deep follicles in the proximal flap), scars were
      better in 95 percent of patients.

PMID- 8982182
TI  - Deep-plane cervicofacial "hike": anatomic basis with dog-ear blepharoplasty.
AB  - The temporal and cheek areas are particularly vulnerable to sun damage and
      therefore to skin cancers. Rotation-advancement flaps are used commonly in the
      reconstruction of these regions following resection of skin cancers. Such flaps
      usually are modifications of the Mustarde, cervicofacial, and Juri flaps. The
      drawbacks to these flaps relate to a random, unpredictable perfusion with skin
      loss at the distal flap tip, a vertically oriented dog-ear that predictably is
      located on the cheek, and the risk of gravitational and cicatricial forces acting
      on the lower eyelid causing ectropion. The deep-plane technique for raising cheek
      flaps, as has been described recently for use in rhytidectomy, allows the plastic
      surgeon to address both drawbacks of the standard cervicofacial flaps. The
      vertical "hike" deep-plane approach addresses both drawbacks of the rotation
      advancement flaps by including better perfusion and superior mobility after
      release of restraining ligaments. We describe the anatomic rationale for the deep
      plane dissection of the cheek in cadaver studies and present our clinical
      technique with a vertical "hike" cheek advancement with removal of the
      horizontally oriented dog-ear as in a blepharoplasty. This single-stage technique
      will be called the deep-plane "hike" flap. The vertically advanced flap must be
      slightly overcorrected by anchoring the flap to the periosteum just above the
      recipient defect. This deep fixation removes all tension from the skin and
      prevents ectropion. This single-stage reconstruction affords excellent cosmetic
      results without compromising any future reconstructive efforts.

PMID- 8982183
TI  - Optic nerve decompression in fibrous dysplasia: indications, efficacy, and
      safety.
AB  - Optic nerve decompression is controversial in posttraumatic visual loss and as a
      prophylactic therapy in fibrous dysplasia involving the optic canal. It is less
      controversial for the treatment of optic nerve compression in fibrous dysplasia.
      Thirteen patients with craniomaxillofacial fibrous dysplasia who underwent 16
      optic nerve decompressions at the Chang Gung Craniofacial Centre for both
      therapeutic (10) and prophylactic (6) indications are reported. One patient
      sustained a clinically useful improvement in vision in response to two
      therapeutic decompressions, and another demonstrated marked improvement after
      therapeutic decompression, with visual acuity improving from 0.4 to 1.0 in the
      affected eye. No patient underwent a permanent deterioration of vision as a
      result of either therapeutic or prophylactic decompression. One patient suffered
      extraocular muscle dysfunction that was corrected with strabismus surgery. A
      review of the literature clarifies the controversies and allows establishment of
      indications for optic nerve decompression.

PMID- 8982184
TI  - Refined frontalis fascial sling with proper lid crease formation for
      blepharoptosis.
AB  - Ptosis of the upper eyelid is a complicated problem, and many surgical techniques
      have been developed for the treatment of ptosis. Frontalis sling with autogenous
      fascial strip for the correction of severe ptosis with poor levator function is
      still well accepted. The treatment necessitates an understanding of the etiology
      of ptosis, detailed history taking, degree of ptosis, the levator function, the
      anatomic basis of the ptosis and lid crease, and a historic review of surgical
      procedures. The refinement of our procedure consists of a circular type of
      frontalis sling with an autogenous fascial strip, harvested from fasciae latae or
      temporalis fascia, with evenly balanced strength and partial lid resection,
      including a semilunar segment of skin flap and orbicularis muscle and moderate
      amount of protruded orbital fat from the orbital septum. The fascial strip is
      anchored simultaneously to the upper margin of the tarsal plate and incision
      margin of the pretarsal lid to produce a proper lid crease. This procedure has
      been successful in the management of 64 lids (46 patients) with a severe degree
      of ptosis and poor levator function. Satisfactory results have been achieved in
      57 lids (89 percent) according to the modified criteria of Berke after an average
      follow-up period of 18.5 months. Most patients (87.5 percent) have mild lid lag
      (1 to 3 mm) after the operation, but 58 lids (90.6 percent) achieved a proper lid
      crease height of 3 to 6 mm.

PMID- 8982185
TI  - Clinical and histologic behavior of exposed porous high-density polyethylene
      implants.
AB  - Reconstruction in the head and neck is difficult and often requires complex
      solutions to restore functional and aesthetic form. While autogenous tissue is
      preferred, many alloplasts have been investigated. These materials, however, are
      foreign bodies, and most alloplasts tolerate exposure and infection poorly. An
      alloplast's in vivo behavior is a function not only of its composition but also
      of its form and macrostructure, as well as the interaction at the host-implant
      interface. Porous high-density polyethylene is well tolerated by surrounding
      tissue, and its porous core is rapidly infiltrated by host tissue. In order to
      further investigate the response of porous high-density polyethylene under
      adverse conditions, we implanted three porous high-density polyethylene disks and
      one silicone disk underneath the dorsal skin in each of 12 rats. The implants
      were exposed at differing times after implantation. After 7 days, the exposed
      areas were either skin grafted or allowed to close by secondary intention.
      Silicone implants all tolerated exposure poorly. Porous high-density polyethylene
      implants exposed soon after implantation also tolerated exposure poorly; however,
      none of these extruded. Porous high-density polyethylene implants exposed after
      the host tissue had invaded the pores tolerated exposure well, healing either by
      secondary intention or by skin grafting. Porous high-density polyethylene is a
      safe and reliable material for use in aesthetic and functional reconstruction of
      the head and neck. Porous high-density polyethylene and possibly other porous
      alloplasts tolerate exposure well once host fibrovascular tissue has invaded the
      implant pores. Further investigation of differing clinical settings and implant
      behavior is currently in progress.

PMID- 8982186
TI  - Masseter muscle atrophy after ostectomy of the mandibular angle in rabbits.
AB  - In order to get information about changes in the masseter muscle when operations
      are performed on the mandibular angle area, we classified 70 New Zealand White
      rabbits into group O (ostectomy) and group D (dissection). In group O we
      performed unilateral ostectomy of the mandibular angle, while in group D we
      performed unilateral dissection of the masseter muscle limited to the mandibular
      angle area. Then we compared morphologic, histologic, and histochemical changes
      in experimental masseter muscles with those in normal control masseter muscles.
      We examined 5 rabbits in each group at the following intervals: 1, 2, 4, 6, 8,
      12, and 24 weeks. In group D (dissection), there were no remarkable changes at
      all examinations. In group O (ostectomy), there was a 30 percent decrease in
      experimental muscle mass compared with control muscle. On examination of muscle
      fiber types, a decrease in type I fibers and an increase in type IIA and IIB
      fibers were noticed (p < 0.05). Each experimental muscle fiber became more
      irregularly and angularly shaped, and mean fiber area also was reduced. Sarcomere
      lengths of experimental muscle fibers were significantly reduced to 80 percent of
      control values (p < 0.05) during the first 4 weeks, but after 6 weeks they were
      lengthened to control values. Collagen and fibrin did not show much difference
      between experimental and control muscles. All these findings imply that masseter
      muscle atrophy after ostectomy of the mandibular angle is not due to connective
      tissue changes but to individual muscle fiber atrophy accompanied by functional
      adaptation of sarcomeres and changes in muscle fiber types.

PMID- 8982187
TI  - Further experiences with the sternocleidomastoid myocutaneous flap: a clinical
      appraisal of 31 cases.
AB  - This paper evaluates the experience of one surgeon with use of the
      sternocleidomastoid myocutaneous flap in 31 consecutive reconstructions in the
      oropharyngeal area. While the complication rate was 52 percent, essentially all
      were due to partial epidermal losses. All flaps healed without requiring
      additional surgery. A review of each of the cases to evaluate the impact of
      previous radiation therapy, location of the blood supply, or concomitant neck
      dissection did not identify any differences in the groups. I conclude that this
      regional flap is readily available and is still useful in selected patients
      needing reconstruction of small wounds in the oropharyngeal area.

PMID- 8982188
TI  - The inframammary extended circumflex scapular flap: an aesthetic improvement of
      the parascapular flap.
AB  - Parascapular free flaps traditionally have been designed obliquely across the
      back, corresponding to the descending branch of the circumflex scapular artery.
      The donor site of this workhorse flap has the drawback of a widened and
      frequently hypertrophic scar. In searching for aesthetic improvements in the
      donor site, we have progressively rotated the axis of this flap in an anterior
      direction. The end result of this modification is the flap we report here: the
      inframammary extended circumflex scapular flap. This flap has a longitudinal axis
      of rotation lying curvilinearly from the inframammary fold to the circumflex
      scapular artery within the triangular anatomic space. We have used this flap in
      20 patients over the past 2 years. The vast majority of these cases were
      deepithelialized flaps with customized extensions of dorsal thoracic fascia to
      correct facial asymmetry. We feel that the inframammary extended circumflex
      scapular artery flap donor-site scar is well hidden within the inframammary fold,
      and that the unavoidable widening and hypertrophy of parascapular and scapular
      flap donor-site scars were minimized compared with traditional flap designs.

PMID- 8982189
TI  - The microvenous valvular anatomy of the human dorsal thoracic fascia.
AB  - The use of free scapular fasciocutaneous flaps for reconstruction of recalcitrant
      grade 6 venous stasis ulcers has shown excellent early success rates. Venous
      refilling times measured postoperatively over the flaps by photoplethysmography
      have noted improvements to normal levels. Preliminary anatomic studies have
      demonstrated valves in the circumflex scapular veins of flaps used in
      reconstruction. The purpose of this study was to investigate and document the
      number, morphology, size, and location of valves in the human dorsal thoracic
      fascia. Ten scapular flaps were obtained from unembalmed cadavers and injected
      with methyl methacrylate. Each flap cast was divided into four parts: proximal,
      right and left, and distal, right and left. We reduced the size of specimens (the
      largest being 24 x 11 mm) and studied them in a scanning electron microscope. We
      identified all valves, estimated the diameter of the corresponding vein,
      calculated the depth of the valvular sinus, and related it to the corresponding
      venous size. Light microscopy and transmission electron microscopy were used as
      assisting tools applied to glutaraldehyde-fixed specimens. Analysis of injected
      specimens showed that valves were most abundant in veins with a luminal diameter
      of 30 to 120 microns (59.3 percent of 905 valves). The depth of valves became
      larger with increasing venous diameter. The sizes of valve sinuses were not
      different for individual valves. Except for veins larger than 1000 microns in
      diameter, there was no significant difference between the number of valves in
      different parts of an individual flap, nor were there significant differences
      between the valve numbers in different flaps. Most valves were bicuspid; only in
      the vein category of 30 to 120 microns were unicuspid valves encountered. Valves
      sometimes were located in series in a short segment of a vein; occasionally, they
      were found at the merging site of two veins. Transmission electron microscopy
      showed that valve leaflets had collagen fibers that ascended toward the tip of
      the leaflet and occasionally were accompanied by elastic fibers. Myofibroblasts
      were regularly present in the valve leaflets. These data show that
      fasciocutaneous flaps from the scapular region have numerous valves (90 valves on
      average in each flap) in the venous microcirculation. The microvenous valves in
      the dorsal thoracic fascia appear to be structurally similar to valves in larger
      veins. These valves may play a role in the improved hemodynamics and promising
      clinical outcome of patients with chronic venous insufficiency who have undergone
      free scapular flap reconstruction.

PMID- 8982190
TI  - Cheng's method for reconstruction of a functionally sensitive penis.
AB  - This article introduces a new surgical method for one-stage reconstruction of the
      penis. It is applied to the reconstruction of the microphallus as well as to
      traumatic cases with the residual stump of the amputated penis not less than 3 cm
      long. By transferring the original glans or the residual penile stump to the
      anterior portion of the newly reconstructed penile body with microsurgical
      techniques, we have thus rebuilt a penis with more satisfactory results in both
      appearance and erotic sensation. Seven patients are reported here who were
      operated on by this method and who have been followed up for 18 months to 10
      years. The good results achieved and the method's advantages over other methods
      are demonstrated and discussed.

PMID- 8982191
TI  - A new technique for distal hypospadias repair: advancement of a distally
      deepithelialized urethrocutaneous flap.
AB  - We report on a new modification technique and the latest results of a procedure
      for treating cases of distal hypospadias with minimal or no chordee called
      advancement of a distally deepithelialized urethrocutaneous flap. This procedure
      incorporates correction of chordee, mobilization of the urethrocutaneous flap,
      and advancement of the flap through a tunnel until it reaches the tip of the
      glans. A total of 30 children underwent treatment using this procedure in our
      clinic. Follow-up of the patients ranged from 2 months to 3 years. Cosmetic
      results were excellent in all the patients. Fistula formation has been observed
      in only one patient, possibly due to a surgical accident. This technique may only
      be applied in distal hypospadias patients with minimal or no chordee in whom the
      meatus is localized to the coronal level or 0.5 cm proximal to it. Patients with
      a short urethra or in whom the meatus is distally localized but with severe
      chordee are not candidates for this technique. In general, this technique is not
      applicable in patients with ventral penile curvature. We would like to emphasize
      that this repair technique allows for simple and safe dissection of the distal
      urethra composed of only mucosa without corpus spongiosum around it. This kind of
      distal urethra can be advanced easily to the tip of the glans penis with the help
      of the dermal component.

PMID- 8982192
TI  - Anatomic study of the superficial perineal neurovascular pedicle: implications in
      vulvoperineal flap design.
AB  - Thirty superficial perineal neurovascular pedicles from 15 formaldehyde-fixed
      female cadavers were dissected and analyzed with the purpose of establishing the
      anatomic basis for the design and elevation of vulvoperineal fasciocutaneous
      flaps based on their anatomic elements. The average internal diameter of the
      superficial perineal artery was 0.53 +/- 0.2 mm, determined by means of an image
      analysis system. Three distinct anatomic patterns of cutaneous arterial
      vascularization were seen bilaterally, and two types of vulvoperineal
      fasciocutaneous flaps are described.

PMID- 8982193
TI  - Radial forearm flap donor-site complications and morbidity: a prospective study.
AB  - One-hundred patients undergoing radial forearm flap reconstruction in the head
      and neck over a 2-year period were followed prospectively to assess complications
      and morbidity associated with the radial flap donor site. Eighty-six patients
      were available follow-up at 3 months and 74 at 1 year (49 fasciocutaneous, 25
      composite). Partial loss of the donor-site skin graft occurred in 14 patients (16
      percent), with exposure of tendons in 11 patients (13 percent). Delay in healing
      of the split-thickness skin graft at the donor site occurred in 19 patients (22
      percent). Fracture of the radius occurred in 6 of 35 patients with composite
      flaps (17 percent). Superficial radial nerve sensation was reduced in 24 patients
      (32 percent) at 1 year. Ten patients (14 percent) reported cold intolerance, and
      21 patients (28 percent) complained of poor aesthetic result. Function of the
      donor arm was restricted in 8 patients (16 percent) in the fasciocutaneous group,
      in 7 patients (36 percent) in the composite group without fracture, and in all
      patients who had a fracture of the radius following harvesting of composite
      flaps. Detailed measurements of forearm circumference, grip strength, pinch
      strength, and wrist movements showed greater reduction in these parameters in
      patients reporting restricted function compared with those reporting normal
      function. It is concluded that there is a low incidence of long-term morbidity
      associated with fasciocutaneous flaps and a higher incidence with composite
      flaps. Fracture of the radius results in reduced function in all cases.

PMID- 8982194
TI  - Vascular and neural anatomy of the thenar area of the hand: its surgical
      applications.
AB  - Thirty fresh cadaver hands were injected with a silicone rubber compound
      (Microfil) and dissected to examine the vascular and neural supplies of the
      thenar area. In 10 specimens, a selective injection technique was used to
      determine the extent of skin territory nourished by the superficial palmar branch
      of the radial artery. The purpose of this study was to clarify the anatomic basis
      for clinical applications of vascularized free- or island-flap transfers from the
      thenar area. The superficial palmar branch of the radial artery was found in all
      hands; the average diameter of the branch measured at its bifurcation site was
      1.4 mm (0.8 to 3.0 mm). The constant area nourished by the superficial palmar
      branch was an area approximately 4 x 3 cm located over the proximal parts of the
      abductor pollicis brevis and opponens pollicis muscles. These results indicate
      that a fasciocutaneous flap from the radial thenar region can be raised based on
      the superficial palmar branch and consistently transferred as a free flap. In 63
      percent of the hands dissected, the superficial palmar branch was connected to
      other arteries in the palm, suggesting that the flap can be transferred as a
      reverse-pedicle island flap in such hands. Innervation of the flap was provided
      chiefly by a branch of the superficial radial nerve. The radial aspect of the
      thenar eminence can provide a new and useful donor source for an innervated and
      vascularized free- or island-flap transfer for reconstruction of various skin
      defects of the volar side of the fingers.

PMID- 8982195
TI  - Metacarpal hand: classification and guidelines for microsurgical reconstruction
      with toe transfers.
AB  - Metacarpal hand refers to the hand that has lost its prehensile ability through
      amputation of all fingers with or without amputation of the thumb. Functional
      restoration can be achieved by a wide variety of microvascular toe transfer
      techniques. When deciding which procedure should be used, careful consideration
      must be given to the level of amputation of the fingers as well as the functional
      status of the remaining thumb. In this article we propose a classification for
      the various patterns of the metacarpal hand along with guidelines for selection
      of the proper toe transfer procedure.

PMID- 8982196
TI  - Carpal tunnel release with short incision.
AB  - A new approach for carpal tunnel release is presented. By means of a specially
      designed guide, it is possible to completely section the carpal ligament with a
      short incision without damaging the carpal contents. When the retinaculum has
      been sectioned and the guide removed by means of three Senn-Miller retractors,
      one proximally and two laterally, the median nerve is seen perfectly. We
      performed an anatomic study to determine where the incision should be made to
      avoid injuring the vascular arch, the cutaneous palmar branch of the median
      nerve, and the ulnar nerve. We present the results obtained in 112 patients
      followed up for 1 year. Complaints about tenderness of the scar disappeared, and
      by the end of the study, patients had regained 126 percent of their preoperative
      grip strength. All patients were able to use their hands shortly after the
      operation, and after 3 weeks, all of them returned to work. We think that by
      using this approach we combine the advantages of the "endoscopic" technique
      (minimal scar, no tenderness, and early recovery) with those of the classic open
      technique (exploration of the carpal contents).

PMID- 8982197
TI  - Efficacy of magnetic resonance angiography in the evaluation of vascular
      malformations of the hand.
AB  - Conventional arteriography has been the accepted standard technique for
      demonstrating the anatomic details in vascular malformations of the hand. The
      technique of magnetic resonance angiography provides detailed anatomy for
      vascular anomalies of the hand without the use of an invasive technique or
      contrast enhancement. When magnetic resonance angiography is combined with
      magnetic resonance imaging, the extent of the lesion with respect to the
      surrounding tissues and the flow characteristics of the lesion can be determined
      noninvasively. In our institution, magnetic resonance angiography has replaced
      conventional arteriography as the technique of choice for the evaluation of these
      lesions. This report evaluates the efficacy of magnetic resonance imaging/
      magnetic resonance angiography in the management of vascular malformations of the
      hand. Ten consecutive patients over 30 months (median age 37 years) underwent
      magnetic resonance imaging/magnetic resonance angiography evaluation after the
      clinical diagnosis of a vascular malformation of the hand was made. Four patients
      in the group had conventional arteriography performed before referral. Magnetic
      resonance imaging/magnetic resonance angiography clearly defined the anatomic
      extent of the lesion, its relationship to surrounding tissues, and the flow
      characteristics in each patient. In the four patients in whom conventional
      arteriography had been performed, the magnetic resonance angiography findings
      matched the arteriographic findings. On the basis of the magnetic resonance
      imaging/magnetic resonance angiography findings, six patients were treated
      nonoperatively with compressive garments and four patients had operative
      treatment (resection of lesion n = 2, digital ray resection n = 2). In this
      series, magnetic resonance imaging/magnetic resonance angiography was efficacious
      in the management of vascular malformations of the hand. This technique provides
      detailed images of both the arterial and venous components of the lesions without
      the requirements of contrast enhancement, ionizing radiation, or an invasive
      procedure. Furthermore, the resectability can be determined based on the extent
      of involvement and the flow characteristics.

PMID- 8982198
TI  - Ischemic tissue oxygen capacitance after hyperbaric oxygen therapy: a new
      physiologic concept.
AB  - In an effort to better understand the effects of hyperbaric oxygen therapy on
      ischemic tissue, we monitored the real-time changes in subcutaneous tissue oxygen
      tension before, during, and after exposure to hyperbaric oxygen treatments. We
      identified an elevation of the tissue oxygen partial pressure to over 300 mmHg
      during the treatment period (up from a baseline mean of 24 mmHg) in a sustained
      ischemia rabbit ear model (n = 22 rabbits). There was no sustained change in
      tissue oxygen tension beyond the period of treatment. This manner of response is
      consistent with several current theories used to explain the mechanism of action
      of hyperbaric oxygen therapy. It is also consonant with our opinion that
      molecular oxygen, when delivered at high pressure, can function both as a
      respiratory metabolite and as a signal transducer. We also studied the impact of
      nontherapeutic 100% oxygen at 1 atm on tissue. The sustained peak tissue oxygen
      tension during such challenges increased in direct proportion to the number of
      hyperbaric oxygen treatments given. The clinical relevance and extension of these
      findings are discussed.

PMID- 8982199
TI  - Microvascular anastomotic thrombosis in experimental diabetes mellitus.
AB  - An experimental model was developed to investigate the effects of glycemic
      control and pentoxifylline administration on microvascular anastomotic patency
      rates in streptozotocin-induced diabetic rats. Diabetes was confirmed by blood
      glucose levels of more than 300 mg/dl prior to administering insulin and/or
      pentoxifylline. Microvascular anastomoses of the femoral artery and vein were
      performed 4 weeks after induction of diabetes. Subsequently, the comparative
      rates of anastomotic thrombosis in diabetic and nondiabetic groups with or
      without insulin or pentoxifylline administration were assessed by direct
      visualization of the anastomotic sites after 4 days. The results suggest that
      hyperglycemia impairs the post-operative patency of microvascular venous
      anastomoses. The diabetic animals maintained under insulin regimens that tightly
      controlled their serum glucose levels (100 to 200 mg/dl) experienced patency
      rates similar to those of nondiabetic controls (p < 0.05). Pentoxifylline
      improved microvenous patency at all levels of hyperglycemia studied, suggesting a
      possible hemorrheologic mechanism for microvascular venous anastomotic thrombus
      formation in diabetic animals.

PMID- 8982200
TI  - Metabolic and contractile responses of fast and slow twitch rat skeletal muscles
      to ischemia and reperfusion.
AB  - The purpose of this study was to investigate the significance of fiber type and
      the effects of the duration of ischemia on metabolic and contractile function of
      skeletal muscle. Under anesthesia, the distal tendons of the fast twitch extensor
      digitorum longus (EDL) and slow twitch soleus (SOL) muscles of the right hindlimb
      of female Wistar rats (250 to 300 gm) were connected to force transducers. Rats
      were assigned to group 1, 1 hour of ischemia; group 2, 2 hours of ischemia; or
      group 3, 3 hours of ischemia (n = 10 for each group). After ischemia, muscles
      were assessed for 2 hours of reperfusion. In both muscles, isometric twitch (Pt)
      and tetanus (Po) and 11 metabolic parameters were measured and compared with
      controls. After 1, 2, or 3 hours of ischemia Pt and Po were significantly (p <
      0.05) lower than preischemic values. After 2 hours of reperfusion, forces and
      metabolic parameters of group 1 recovered to preischemic levels. However,
      contractile function of either muscle failed to recover fully after 2 hours of
      ischemia and 2 hours of reperfusion (SOL: Pt = 43.7 +/- 12 percent of initial;
      EDL: Pt = 32.2 +/- 9.2 percent) or after 3 hours of ischemia and 2 hours of
      reperfusion (SOL: Pt = 26.8 +/- 11 percent of initial; EDL: Pt = 19.3 +/- 6.8
      percent). Although ADP and AMP recovered to preischemic levels in both muscles
      after 2 hours of ischemia and 2 hours of reperfusion, ATP recovered to just 70
      percent in the soleus muscles (13.4 +/- 1.7 mmol/kg dry weight) and 60 percent in
      the extensor digitorum longus muscles (17.93 +/- 4.1 mmol/kg dry weight). After 3
      hours of ischemia and 2 hours of reperfusion, ATP was further significantly (p <
      0.05) decreased in the soleus muscles (48 percent initial) but not in the
      extensor digitorum longus muscles. Significant partial correlation coefficients
      (p < 0.005) were obtained between ATP levels and Pt (SOL: r = 0.757; EDL: r =
      0.619) or Po (SOL: r = 0.810; EDL: r = 0.759). For this rat hindlimb model, we
      conclude that both fiber type and the duration of ischemia significantly affect
      metabolic and contractile function.

PMID- 8982201
TI  - Acute adenosine treatment is effective in augmentation of ischemic tolerance in
      muscle flaps in the pig.
AB  - The objective of the present project was to investigate the efficacy and
      mechanism of acute (10-minute) adenosine treatment for augmentation of ischemic
      tolerance in muscle flaps in pigs. Varying doses of adenosine were infused into
      28 latissimus dorsi muscle flaps through the axillary artery (0, 0.5, or 2.0 mg
      per flap) and 22 gracilis muscle flaps through the medial circumflex femoral
      artery (0, 10, or 20 mg per flap) over 10 minutes. Ten minutes after adenosine
      infusion, these muscle flaps were subjected to 4 hours of sustained warm global
      ischemia. In addition, one group of latissimus dorsi muscle flaps (n = 6)
      received a 10-minute intraarterial adenosine infusion (0.5 mg) at the beginning
      of reperfusion. Muscle biopsies (n = 4 or 5) for adenosine triphosphate (ATP)
      analysis were obtained before and after adenosine infusion and at the end of 4
      hours of ischemia. The extent of muscle infarction was assessed at 48 hours of
      reperfusion by the tetrazolium dye staining technique. Muscle blood flow in
      latissimus dorsi muscle flaps was measured at the end of adenosine infusion (0 or
      0.5 mg per flap, n = 8) by the radioactive microsphere (15-microns) technique. It
      was observed that adenosine, at all doses tested, significantly (p < 0.05)
      reduced the extent of muscle infarction in latissimus dorsi muscle flaps
      (control, 40.3 +/- 2.2 percent; 0.5 mg, 20.6 +/- 1.6 percent; 2.0 mg, 18.2 +/- 1
      percent) and gracilis muscle flaps (control, 31.0 +/- 1.5 percent; 10 mg, 14.3 +/
      3 percent; 20 mg, 11.6 +/- 1.2 percent). Preischemic adenosine treatment (0.5 mg
      per flap) was associated with maintenance of a significantly (p < 0.05) higher
      muscle content of ATP in latissimus dorsi muscle flaps at the end of 4 hours of
      ischemia compared with saline-treated ischemic controls. Postischemic adenosine
      treatment did not protect latissimus dorsi muscle flaps against infarction.
      Furthermore, adenosine treatment did not have any significant effect on mean
      systemic arterial blood pressure or muscle blood flow in latissimus dorsi muscle
      flaps. It is concluded that acute (10-minute) preischemic adenosine treatment is
      effective in augmentation of ischemic tolerance in muscle flaps and that this
      protective effect of adenosine may be, at least in part, the result of slowing
      muscle ATP depletion during sustained ischemia. The possible mechanisms of this
      adenosine-induced energysparing effect are discussed.

PMID- 8982202
TI  - The effect of the delay phenomenon on the vascularity of rabbit abdominal
      cutaneous island flaps.
AB  - The beneficial effects of the delay phenomenon have been evaluated extensively
      and are widely known. However, no study has quantified the vascular changes seen
      in an abdominal cutaneous island flap following a surgical delay by vascular
      pedicle ligation. We evaluated the effect of unilateral superficial inferior
      epigastric and deep inferior epigastric pedicle ligation on the vascularity of a
      rabbit abdominal cutaneous island flap. Thirty rabbits underwent a left
      superficial inferior epigastric and deep inferior epigastric pedicle ligation as
      a delay procedure. A 19 x 15 cm abdominal cutaneous island flap was elevated at
      the time of sacrifice, based solely on the right superficial inferior epigastric
      pedicle. The flap vasculature was then evaluated by methylene blue injection and
      lead oxide microangiography at 0, 5, 10, 15, 21, and 27 days following the delay
      procedure. Methylene blue studies revealed perfusion of only the right
      (nonligated) side of the flap on day 0 and perfusion of the entire flap by day
      15. This "capture" of the left (ligated) superficial inferior epigastric artery
      angiosome by day 15 could only have been achieved through enhanced cross-midline
      perfusion. Lead oxide microangiography revealed an increase in the number of
      vessels from day 0 to day 27 on both the ligated and nonligated sides in all the
      following: the number of large "choke" vessels (> 0.5 mm) crossing the flap
      midline, total number of vessels (all sizes) crossing the flap midline, and total
      number of vessels (all sizes) at the medial aspect of the right and left
      superficial inferior epigastric artery angiosomes. A statistically significant
      increase in these vessels was not seen until day 21. The effect of the delay
      phenomenon was significantly greater on the ligated side compared with the
      nonligated side. The areas of the flap that were relatively more ischemic
      following left superficial inferior epigastric pedicle ligation (medial aspect of
      the caudad half of the left superficial inferior epigastric artery angiosome)
      showed greater increases in vascularity with the delay procedure than did areas
      of lesser ischemia (medial aspect of the cephalad half of the right superficial
      inferior epigastric artery angiosome).

PMID- 8982203
TI  - The effect of the delay phenomenon on the vascularity of rabbit rectus abdominis
      muscles.
AB  - The transverse rectus abdominis muscle (TRAM) flap has become the "gold standard"
      for autogenous breast tissue reconstruction. Complications are reported in 10 to
      40 percent of patients undergoing this procedure, and many are related to soft
      tissue necrosis secondary to ischemia. Various methods have been proposed to
      improve TRAM flap survival, including surgical delay of the flap. The beneficial
      effects of the delay phenomenon have been well established in laboratory studies
      and clinical evaluations. Many investigators agree that the delay phenomenon will
      enhance arterial inflow and venous outflow from the TRAM flap. No study has
      quantified the changes seen in the rectus abdominis muscle following a delay
      procedure. In this prospective, controlled, and blinded experiment, we evaluate
      the effect of a unilateral superficial inferior epigastric and deep inferior
      epigastric artery and vein ligation on the vascularity of the rectus abdominis
      muscles in rabbits. Thirty-eight rabbits underwent a left superficial inferior
      epigastric and deep inferior epigastric pedicle ligation as a delay procedure.
      The rectus abdominis muscle vasculature was then evaluated by lead oxide
      microangiography at 0, 5, 10, 15, 21, and 27 days following the delay procedure.
      Magnification (x 2) was used to count the number of vessels at the periphery of
      the deep inferior epigastric artery angiosomes in the microangiograms. An
      increase in the number of vessels from day 0 to day 27 was seen on both the
      ligated and nonligated sides in all the following: the number of large (> 0.5 mm)
      "choke" vessels and total number of vessels (all sizes) crossing the abdominal
      wall midline and the total number of vessels (all sizes) at the medial, superior,
      and lateral aspects of the right and left deep inferior epigastric artery
      angiosomes. A statistically significant increase in these vessels was not seen
      until day 21. The effect of the delay phenomenon was significantly greater on the
      ligated side compared with the nonligated side. The areas of the rectus abdominis
      muscles that were relatively more ischemic following left deep inferior
      epigastric pedicle ligation (medial aspect of the left deep inferior epigastric
      artery angiosome) showed greater increases in vascularity with the delay
      procedure than did areas of lesser ischemia (lateral aspect of the right deep
      inferior epigastric artery angiosome).

PMID- 8982204
TI  - Two trains, one track.

PMID- 8982205
TI  - Plastic and reconstructive surgery of the craniomaxillofacial and head and neck
      region: an interdisciplinary field.

PMID- 8982206
TI  - The 1996 clinician of the year address.

PMID- 8982208
TI  - A new flap for nasal tip reconstruction.
AB  - Aesthetic reconstruction of tumor defects of the nasal tip and supratip areas
      remains a challenge. Because of our dissatisfaction with the current
      reconstructive options, we have developed a modification of the nasalis flap
      based on the angular artery for the management of nasal tip defects. This is an
      axial flap-pattern that rotates toward the midline and nasal tip, leaving donor
      scars in the nasojugal and alar creases. A second rotation flap from the alar
      groove fills the donor defect in the nasojugal region to minimize scarring. We
      have utilized this flap 19 times in 18 consecutive patients with nasal tip and
      supratip tumor defects with follow-up ranging from 10 to 72 months. Donor scars
      are well concealed and nasal contour is minimally altered. Color and texture
      matches are excellent, and the pincushion deformity has been eliminated. On the
      basis of these results, we believe the modified nasalis flap is ideally suited
      for nasal tip reconstruction.

PMID- 8982207
TI  - Tumescent liposuction complicated by pulmonary edema.
AB  - In tumescent liposuction, large volumes of dilute lidocaine and epinephrine are
      infused subcutaneously to prepare fat for extraction. Reported cardiopulmonary
      complications of tumescent liposuction have been few, and the anesthetic and
      hemodynamic advantages are several. We report an instance of pulmonary edema in a
      healthy 55-year-old male body-builder who received 7900 cc subcutaneous and 2200
      cc intravenous fluid. With normal cardiopulmonary and renal function, the patient
      responded promptly to intravenous diuretics without sequelae. Out of over 900
      patients who have had tumescent liposuction with up to 15 liters infused
      parenterally, this is the first case of pulmonary edema.

PMID- 8982209
TI  - Internal mammary silicone lymphadenopathy mimicking recurrent breast cancer.
AB  - This case describes a unique complication of silicone breast implantation that is
      previously undocumented. Internal mammary silicone lymphadenopathy mimicking
      breast cancer recurrence represents an important new clinical entity. The
      diagnosis and management of this clinical enigma are challenging. In our patient,
      videothoracoscopy proved to be minimally invasive and allowed complete resection
      of the entire chain of pathologic nodes. Explantation of the silicone prostheses
      and complete capsulectomy are indicated. Light microscopy alone can suggest the
      diagnosis of silicone lymphadenopathy. Infrared spectral analysis can be a
      helpful adjunct to allow an unequivocal diagnosis.

PMID- 8982210
TI  - Unilateral cleft lip repair in the presence of a vermilion hemangioma.
AB  - This case describes a repair of a unilateral cleft lip complicated by a lip
      hemangioma. The relevant issues regarding timing of the repair include safety of
      the procedure by minimizing blood loss during excision of the hemangioma and
      minimizing anesthesia risk. In obtaining a lasting cosmetic result, excision of
      the hemangioma would need to be done when the potential for residual tumor growth
      would be least likely (during tumor involution). Finally, the difficult issue of
      psychosocial concerns would balance the need for traditional early cleft repair
      with a definitive repair prior to increased social interaction in school. All
      these concerns were met with a delayed single-stage repair after partial
      involution of the hemangioma. We feel that a single-stage excision and lip repair
      is an acceptable option. It is reasonable to delay the cleft lip repair until
      significant involution of the hemangioma has occurred. An acceptable aesthetic
      result is obtainable.

PMID- 8982211
TI  - One-stage reconstruction of established facial paralysis using a rectus abdominis
      muscle transfer.
AB  - A free vascularized rectus abdominis muscle graft with a long motor nerve was
      used for reconstruction of unilateral established facial paralysis in one stage.
      Regarding the procedure, the pedicle vessels were anastomosed to the recipient
      vessels in the ipsilateral face, and the motor nerve of the muscle was sutured to
      the contralateral facial nerve. The advantages of using the rectus abdominis
      muscle are as follows: (1) the muscle is very thin, not bulky, (2) the muscle can
      be split easily to reduce the volume, (3) the intercostal nerve is long enough
      (more than 20 cm) to reach the contralateral facial nerve for suturing, (4) the
      pedicle vessels are large and long, (5) it is possible to carry out simultaneous
      operations with two teams, and (6) the donor-site morbidity is minimal. The
      disadvantages of this method are that complicated surgical dissection is required
      to obtain a motor nerve and that a postoperative abdominal hernia may occur.

PMID- 8982212
TI  - Transverse lag screw fixation of the midline mandibulotomy.
AB  - Transverse lag screw osteosynthesis of the midline mandibulotomy is a rapidly
      performed technique that results in reestablishment of mandibular integrity and
      avoids placement of hardware directly beneath a suture line. We have performed
      transverse lag screw osteosynthesis in four patients over the past 14 months. All
      patients received postoperative radiotherapy. Soft-tissue and bone healing have
      been uneventful.

PMID- 8982213
TI  - Single-anastomosis femoral arteriovenous shunt as recipient vessels for free-flap
      reconstruction of a massive lumbosacral wound.
AB  - In any reconstructive microsurgical procedure, an adequate recipient circulation
      is required. None is readily available when reconstructing problem wounds of the
      lumbosacral spine, leading in some cases to the use of long vein grafts to the
      axilla to provide vascular access. A case of a massive back wound that was
      reconstructed microsurgically with a prefabricated preliminary arteriovenous
      shunt, based on the femoral vessels, is presented. This method takes advantage of
      the normal anatomic arrangement of the saphenous venous system, requires only one
      anastomosis, and provides an accessible vascular supply. The technical advantages
      of the procedure are discussed.

PMID- 8982214
TI  - Synovitis and silicone joint implants: a summary of reported cases.

PMID- 8982215
TI  - TRAM flap breast reconstruction and adriamycin therapy.

PMID- 8982216
TI  - Breast reduction under local anesthesia with intravenous sedation.

PMID- 8982217
TI  - Transaxillary submuscular breast augmentation and subcutaneous fibrous bands.

PMID- 8982218
TI  - Fibrous bands following subpectoral endoscopic breast augmentation.

PMID- 8982219
TI  - Subcutaneous fibrous banding after transaxillary subpectoral endoscopic breast
      augmentation.

PMID- 8982220
TI  - Scars at cannula sites for liposuction.

PMID- 8982221
TI  - Silicone breast implant safety: physical, chemical, and biologic problems.

PMID- 8982222
TI  - Reinsertion of the pectoralis minor into the gracilis free transfer in brachial
      plexus reconstruction.

PMID- 8982223
TI  - Clinical evaluation of facial morphology in cleft lip palate patients.

PMID- 8982224
TI  - An economical axial-pattern flap necrosis model.

PMID- 8982225
TI  - Emergency text slide production.

PMID- 8982226
TI  - Reverse temporalis muscle flap: treatment of large anterior cranial base defect
      with direct intracranial nasopharyngeal communication.

PMID- 8982227
TI  - Hyperpigmented burn injuries of the face: treatment with the Q-switched ruby
      laser.

PMID- 8982228
TI  - Coral in malar augmentation: complications in our experience.

PMID- 8982229
TI  - Random-pattern lower leg fasciocutaneous flap.

PMID- 8982230
TI  - Dental alginate for taking impressions of the nose prior to rhinoplasty.

PMID- 8982231
TI  - Absence of hernia after removal of Gore-Tex.

PMID- 8982232
TI  - The first description of the free vascularized bone transplant.

PMID- 8982233
TI  - Simple appliance for reduction of facial skeletal fractures.

PMID- 8982234
TI  - Breast reconstruction in patients after chest-wall irradiation.

PMID- 8982235
TI  - Should we ban the use of powder-coated gloves in operations involving prosthetic
      devices?

PMID- 8982236
TI  - Case report of asymmetrical striae following breast augmentation.

PMID- 8982237
TI  - Mnemonics in plastic surgery.

PMID- 8982238
TI  - Precautions in the use of the laser for blepharoplasty.

PMID- 8982239
TI  - Antigenic determinants in type 1 diabetes mellitus. Review article.
AB  - Type 1 diabetes mellitus (IDDM) is a disease caused by the autoimmune destruction
      of insulin-producing pancreatic beta cells that takes place in genetically
      predisposed individuals. The results of the studies performed so far during the
      search for "the target antigen" in beta cell autoimmunity have indicated that,
      unlike many autoimmune disorders, type 1 diabetes appears to be the result of an
      autoimmune response to a multiplicity of autoantigens. Autoantibodies and
      autoreactive T lymphocytes reacting with islet target molecules of protein or
      glycolipid nature have been shown in the circulation of individuals and of animal
      models of type 1 diabetes (NOD mouse and BB rat) before and at the onset of the
      disease. In the present article we have reviewed the data available on the
      antigenic determinants in type 1 diabetes, with particular reference to those
      recognized by autoantibodies which represent the best available predictive marker
      of future disease development in large scale screening studies.

PMID- 8982240
TI  - Structure, growth and cell proliferation of human osteosarcoma and malignant
      fibrous histiocytoma xenografts in serial transplantation in nude mice.
AB  - Tumour specimens from one patient with osteosarcoma and one with malignant
      fibrous histiocytoma were transplanted in serial passages in nude mice.
      Structure, growth and cell kinetics of the xenografts were studied in order to
      assess the validity of the two tumour models. Cell proliferation was analysed
      using in vivo labelling with the thymidine analogue iododeoxyuridine (IdUrd) and
      the IdUrd labelling index (LI) was determined by immunohistochemistry. The DNA
      index (DI) was examined by flow cytometry. The c-myc oncoprotein expression was
      studied by immunohistochemistry. More intense proliferation was observed in the
      peripheral parts of the tumours. There was no correlation between tumour growth
      and cell proliferation in the two tumour groups. Stability of the tumour models
      was indicated by low intrapassage and interpassage variations of DI, LI, and
      volume doubling time, and also by retained histopathological characteristics and
      c-myc staining patterns of donor patients' tumours during serial transplantation.

PMID- 8982241
TI  - Expression of tumor-related antigens Lewis(a) Lewis(b), X, Y, Span-1 and CEA in
      relation to differentiation and prognosis in rectal adenocarcinomas.
AB  - Expression of Le(a) (Lewis(a)), Le(b) (Lewis(b)), X (Lewis X), Y (Lewis Y), SPan
      1 and CEA was detected by an immunohistochemical method using a panel of
      antibodies in paraffin-embedded materials from 45 rectal adenocarcinomas and the
      corresponding normal mucosa. The relationships between antigen expression and
      grade of differentiation and survival were analyzed. Compared to the expression
      in normal mucosa, the expression of Le(a) was decreased in tumors while the
      expression of Le(b), X, Y. SPan-1 and CEA was increased. The expression of Le(a)
      and SPan-1 was associated with the grade of differentiation (p = 0.0001 and p =
      0.02, respectively). Positive expression of Le(a) and SPan-1 correlated with poor
      prognosis (p = 0.0001 and p = 0.002, respectively), but positive expression of Y
      predicated favorable prognosis (p = 0.01). Our findings indicate that some of the
      tumor-related antigens might provide information important for the diagnosis,
      determining histologic differentiation and prognosis in rectal adenocarcinomas.

PMID- 8982242
TI  - Detection of apoptotic cells and expression of Ki-67 antigen, Bcl-2, p53
      oncoproteins in human parathyroid adenoma.
AB  - Presence of apoptotic cells and immunoreactivity to Ki-67, bcl-2 and p53 were
      studied in 20 cases of parathyroid adenoma. To determine apoptosis, the DNA nick
      end labeling method was used. 85% of the parathyroid adenomas were found to
      harbor apoptotic cells. All of the 20 adenomas contained Ki-67 immunoreactive
      cells. Proliferative activity was not more confined to nodular than to diffuse
      areas, but there was a highly significant difference in Ki-67 immunoreactivity
      between adenomatous tissue and the residual rim of normal tissue outside the
      adenoma. No Ki-67 immunoreactive cells were found in two normal parathyroid
      glands used as controls. All but one of the adenomas (95%) demonstrated
      immunoreactivity to bcl-2, but expression of p53 was detected in only a few
      adenomas (15%). There was a significant relationship between the adenoma weights
      and both Ki-67 and bcl-2. This study suggests that parathyroid adenomas contain
      cell populations with proliferative activity (clonal proliferation), but the weak
      immunoreactive expression of p53 combined with the relatively strong expression
      of bcl-2 might contribute to a slow glandular growth.

PMID- 8982243
TI  - Recovery of skeletal muscle after immobilization of rabbit hindlimb. A light
      microscopic study.
AB  - The histopathology of the deep portion of the vastus intermedius (VIP) muscle
      from 13 rabbit hindlimbs immobilized in shortened position for 2-2.5 (n = 4), 3
      (n = 3), 14 (n = 3) and 28 (n = 3) days and VIP muscles from 13 rabbit hindlimbs
      immobilized for the same time periods and subsequently remobilized for 4 weeks
      were compared. After 3 days of immobilization the VIP muscles displayed a 15% (p
      < 0.004) decline in muscle fibre diameter. By 2 weeks of immobilization fatty
      change was prominent and muscle fibre diameters had decreased to 56% (p < 0.0001)
      of control values. By 4 weeks of immobilization severe fibrotic damage of
      myofibres was observed and fibre diameters had decreased to 47% (p < 0.0001) of
      control values. Three days of immobilization followed by 4 weeks of
      remobilization led to marked fatty change as well as an increase in connective
      tissue in the affected VIP muscles. The muscle fibre diameter in these muscles
      was 71% (p < 0.0001) compared to the VIP immobilized for 3 days and 61% (p <
      0.0001) compared to the control muscles. By 2-4 weeks of immobilization the
      subsequent remobilization did not aggravate the initial damage. We conclude that
      the morphology of VIP muscle immobilized for 3 days suffers more during a
      subsequent remobilization period than those immobilized for 14-28 days. These
      findings focus attention on the mechanisms operating at the onset of disuse
      muscle atrophy.

PMID- 8982244
TI  - An experimental model for acute poststreptococcal glomerulonephritis in mice.
AB  - A number of factors have been implicated in the pathogenesis of acute
      poststreptococcal glomerulonephritis (APSGN). The lack of a reliable animal model
      has made it difficult to further examine the role of these factors in the
      pathogenetic process. In this report, we present a tissue cage model in mice for
      the study of APSGN. Morphological and immunohistological changes in the kidney,
      resembling those of APSGN in man, were induced at high frequency in the
      experimental model after infection with group A streptococcal nephritis isolates.
      Nephritis-associated strain induced hypercellularity, occlusion of capillaries,
      and C3 deposition at high frequencies compared to the changes induced in animals
      infected with a non-nephritis-associated strain and non-infected controls. In
      animals infected with a nephritis isolate, hematuria and proteinuria were also
      detected. If penicillin treatment was initiated on the third day of infection,
      the development of the nephritis process was prevented. Streptokinase, as well as
      preabsorbing antigen and streptococcal pyrogenic exotoxin B (SpeB), have been
      implicated in the pathogenesis of APSGN. These proteins, as well as SpeA and
      SpeF, were detected in the fluids of the infectious focus, regardless of the
      origin of the strains and whether or not glomerulonephritis was seen. Antibodies
      to streptokinase were evoked in the majority of the infected animals. This immune
      response did not correlate with the nephritic process since hypercellularity was
      also seen in animals which lacked detectable streptokinase antibodies. The
      results show that the mouse tissue cage model can be used to study APSGN and to
      evaluate factors involved in the pathogenesis of the disease.

PMID- 8982245
TI  - Sertoli cells, but not tumor cells, of seminoma in situ express ICAM-1.
AB  - Tumor and surrounding testicular tissue from six seminomas and one combined
      seminoma/embryonal carcinoma were examined for the expression of ICAM-1, VCAM-1
      and ELAM-1. This was done by immunohistochemical staining of frozen samples using
      monoclonal antibodies and the avidin-biotin/ peroxidase or alkaline phosphatase
      staining method. ICAM-1 was expressed by Sertoli cells of intratubular germ cell
      neoplasia, but not by any of the cells in normal seminiferous epithelium, or by
      neoplastic germ cells whether invading or not. In addition inflammatory cells and
      endothelium expressed ICAM-1. VCAM-1, and also occasionally ELAM-1, was expressed
      only on endothelial cells in and outside the tumors. These results are discussed
      in relation to lymphocytic infiltration and immune surveillance of seminomas and
      T-cell tolerance to the antigens of the immunologically privileged seminiferous
      epithelium.

PMID- 8982247
TI  - Mast cells in human coronary arteries; is there any correlation with luminal
      narrowing?
AB  - Histamine in the human coronary arteries is harboured in mast cells and possibly
      in a non-mast cell store. Upon histamine exposure atherosclerotic coronary
      arteries react differently than normal coronary arteries, and histamine has been
      proposed to provoke vasospasms, ischaemia and sudden cardiac death. Previous
      reports have indicated a correlation between the mast cell density and the
      histamine content on the one hand and the degree of atherosclerosis on the other
      hand. Since previous reports applied visual assessment of the luminal narrowing
      only, we reexamined these results utilising planimetric methods. The study was
      accomplished by examining coronary arteries from autopsy cases (50-70 years, N =
      29) with a diagnosis of sudden death, myocardial infarction or a non-cardiac
      cause. The mast cell density was calculated as the ratio between the mast cell
      count and the adventitial area as seen by light microscopy, and was compared to
      the degree of luminal narrowing. We were not able to find any correlation between
      the mast cell density and the luminal narrowing. The myocardial infarction group
      had the most severe degree of luminal narrowing, but there was no significant
      difference in mast cell density between the groups. We therefore question the
      previous notion that there is a correlation between the adventitial mast cell
      density in the coronary arteries and the luminal narrowing. Earlier reports may
      have been biased by visual assessment and by erroneously treating several
      measurements from the same person as independent samples.

PMID- 8982246
TI  - The role of the Lps gene in experimental ulcerative colitis in mice.
AB  - The effects of the Lps gene on the development of experimental ulcerative colitis
      were studied in two genetically different mouse strains: C57B1 and C3H. Acute
      colitis was induced by adding 3% dextran sulfate sodium (DSS) to the drinking
      water for a 7-day (C57B1 and C3H) or a 10-day (C57B1) experimental period.
      Although the DSS treatment initiated the same type of morphological changes in
      the colon in all groups of mice, an earlier onset and persistent intestinal
      bleeding occurred in the Lpsn mice (sensitive to lipopolysaccharide, LPS) in
      comparison with the Lpsd mice (hyporesponsive to LPS). Rectal bleeding appeared
      on day 7 in 90% of the Lpsn compared to 13% of the Lpsd mice (p < 0.0001). In
      C57B1 mice, followed for three additional days, 50% of the Lpsn mice died and the
      surviving animals showed as well as rectal bleeding a large number of Gram
      negative bacteria in the liver and spleen. In contrast, the Lpsd mice of the
      C57B1 strain appeared unaffected by the treatment, although a transient rectal
      bleeding occurred in 90% on day 8. Also, significantly fewer Gram-negative
      bacteria were found in the liver and spleen. Even though significantly increased
      serum endotoxin levels were seen in all DSS-treated groups compared to controls
      on day 7, the serum levels of TNF alpha were significantly increased only in the
      Lpsn mice. In DSS-induced colitis the Lpsn genotype conferred on the mice an
      increased LPS susceptibility, resulting in an augmentation of the inflammatory
      response to Gram-negative bacteria and their endotoxins. The results suggest that
      LPS-induced host effector mechanisms significantly enhanced the intestinal
      bleeding, systemic inflammatory response, and mortality in mice with DSS-induced
      colitis. In addition, the host defense against the invading and systemically
      spread bacteria most probably involved additional genes.

PMID- 8982248
TI  - Migration of IL-2-activated natural killer cells in vitro: influence of
      extracellular matrix proteins.
AB  - An experimental set-up for estimating a) cellular migration under agarose and b)
      response to chemoattractant gradients built up in the agarose was used in order
      to explore the behavior of adherent interleukin-2 (IL-2)-activated natural killer
      (A-NK) cells on cell culture plastic and after coating with extracellular matrix
      (ECM) constituents. A-NK cells were deposited in wells in the agarose and
      directed migration, chemotaxis, towards aggregates and suspensions of B16F10
      melanoma cells, suspensions of YAC-1 cells, and tumor-conditioned media, all
      deposited in wells at a 2.5 mm distance, was tested. A-NK cell chemotaxis was
      exclusively observed when B16F10 aggregates were used as attractants. The
      substrate influenced chemotaxis considerably, untreated plastic surface being
      most favorable for a chemotactic response, followed by laminin, fibronectin, and
      collagen IV pretreatments. Coating with reconstituted basement membrane matrix
      (Matrigel) gave lesser random movements, chemokinesis, of A-NK cells than coating
      with the purified components laminin and collagen IV, and the least motile
      response was obtained after collagen I pretreatment. These in vitro observations
      indicate that melanoma cell aggregates release humoral factors of a probably
      short-lived nature with a chemoattractant effect on A-NK cells, and that ECM
      composition influences migratory response, both conclusions with a bearing on the
      understanding of A-NK cell infiltration into tumors in vivo.

PMID- 8982251
TI  - Characterization of the human germ cell nuclear factor gene.
AB  - A cDNA clone encoding the germ cell nuclear factor, GCNF, a member of the nuclear
      receptor superfamily has been isolated from the human embryonal carcinoma cell
      line NT2/D1. Sequencing of this clone reveals an open reading frame encoding a
      476 amino acid protein. A comparison of the amino acid sequence of the human GCNF
      with its mouse homologue shows only six amino acid exchanges in the whole protein
      and a deletion in the amino-terminal region. Northern blot analysis demonstrates
      that the expression in the testis is conserved.

PMID- 8982250
TI  - Molecular cloning of a cDNA encoding a Xenopus laevis 70-kDa heat shock cognate
      protein, hsc70.II.
AB  - We have isolated and sequenced a full-length cDNA clone encoding a Xenopus laevis
      70 kDa heat shock cognate protein, hsc70.II. The protein coding region exhibited
      high identity with Xenopus hsc70.I (94%), suggesting that the two genes are the
      result of a genomic tetraploidization event which occurred in Xenopus over 30
      million years ago. Also, hsc70.II displayed a high level of identity with
      mammalian hsc70. However, the identity of Xenopus hsc70.II cDNA with Xenopus
      hsp70 was only 82%. At the carboxyl end of the hsc70.II protein, the identity
      with hsc70.I was 85%, while the identity for hsp70 was only 58%. These data
      support the theory that the inducible and constitutive members of the hsp70
      family diverged well before the emergence of amphibians. Also, hsc70.II contains
      a number of conserved elements including an ATP-binding domain, a nuclear
      localization signal and the carboxyl terminal motif, EEVD, which may have a role
      in chaperone function.

PMID- 8982249
TI  - Sequence specific binding of cytosolic proteins to a 12 nucleotide sequence in
      the 5' untranslated region of FMR1 mRNA.
AB  - The 5' untranslated region of human FMR1 mRNA is highly conserved, including a 26
      nucleotide sequence containing a tandem 12 nucleotide repeat of
      (G/C)CU(C/G)CCGG(G/A)G(G/C)(G/C) which predates the evolutionary divergence
      between birds and mammals. We show here that this 12 nucleotide sequence in FMR1
      mRNA is a specific binding site for small (< 20 kDa) cytosolic proteins of rat
      brain. Point mutation analysis identified two guanine residues in this 12
      nucleotide repeat which are essential for protein binding. The 12 nucleotide
      motif sequence was found in the 5'UTR of at least 15 other genes and could be a
      common target site for these cytosolic RNA-binding proteins.

PMID- 8982252
TI  - A cDNA encoding a putative 37 kDa leucine-rich repeat (LRR) protein, p37NB,
      isolated from S-type neuroblastoma cell has a differential tissue distribution.
AB  - In human neuroblastoma cells in culture, three morphologically distinct types of
      cells are observed: neuroblastic N-type cells, Schwannian S-type cells, and
      intermediate I-type cells. To investigate the differences in gene expression
      between N-type LA1-55N and S-type LA1-5S cells of the human neuroblastoma cell
      line LA-N-1, we constructed a subtractive cDNA library from LA1-5S cells. One of
      the genes that are expressed more in S-type cells than in N-type cells was
      identified as previously undescribed and is the focus of this report. We cloned a
      full-length cDNA of this gene, p37NB, and determined its sequence. A homology
      search against the GenBank database showed that this was from a novel gene
      encoding a putative 37 kDa leucine-rich repeat (LRR) protein. Northern blot
      hybridization and RT-PCR showed that the p37NB gene was differentially expressed
      in S-type compared to N-type cells of a few neuroblastoma cell lines.

PMID- 8982253
TI  - Cotranscription of a GTPase gene from the cyanobacterium Synechocystis PCC 6803
      and a P-type Ca(2+)-ATPase gene.
AB  - A GTPase gene adjacent to the Ca(2+)-ATPase gene from Synechocystis PCC 6803 has
      been sequenced. It encodes for a protein of 456 amino acids revealing high
      homology to so-called 50K proteins of Bacillus subtilis and Pseudomonas putida.
      Cotranscription of GTPase and Ca(2+)-ATPase genes has been shown by reverse
      transcription PCR.

PMID- 8982254
TI  - Molecular cloning of a cDNA encoding an antigen which is salt-stably attached to
      centrosomes.
AB  - A monoclonal antibody (MAB 2A8) was used for expression-cloning of a complete
      cDNA (1133/5) to a mRNA (3 kb) encoding a murine 76 kDa polypeptide. The N
      terminal section of the polypeptide is composed of domains capable to form alpha
      helical coiled-coils. Its C-terminus is proline-rich and has characteristics of
      the Src homology region 3 (SH3). Affinity-purified antibodies to a recombinant
      section of the protein show that the antigen is salt-stably associated with the
      centrosome throughout the cell cycle.

PMID- 8982255
TI  - Cloning and functional characterization of a rat urea transporter: expression in
      the brain.
AB  - A cDNA coding for a rat urea transporter is described. The 1242 bp open reading
      frame codes for a 414 amino acids protein with 77.0% and 60.7% identity with the
      human UT11 and the rat UT2, respectively. When expressed in Xenopus oocytes, the
      protein induces a 10-fold rise in urea permeability, inhibited by mercurial
      reagents and phloretin. The rUT11 mRNA is massively expressed in the brain.

PMID- 8982256
TI  - hDIP--a potential transcriptional regulator related to murine TSC-22 and
      Drosophila shortsighted (shs)--is expressed in a large number of human tissues.
AB  - We have cloned a 420 bp cDNA from a human fetal brain cDNA library in lambda
      encoding the human homologue of a DSIP-immunoreactive leucine zipper protein
      (DIP) isolated from porcine brain. The derived human protein (hDIP) shares a
      significant sequence identity with parts of the murine TSC-22 and Drosophila shs,
      both proteins which are discussed as functioning as transcriptional regulators. A
      similar role of hDIP is partially confirmed by the results of an RT-PCR analysis,
      demonstrating the widespread distribution of the protein among different human
      tissues.

PMID- 8982258
TI  - Promoter of the gene encoding the bovine catalytic subunit of cAMP-dependent
      protein kinase isoform C beta 2.
AB  - Genomic sequences flanking the 5' end of the cDNA encoding isoform C beta 2 of
      the catalytic subunit of bovine cAMP-dependent protein kinase were cloned,
      sequenced and analyzed for promoter activity and transcription initiation sites.
      A region of 913 bp upstream the translation initiator ATG was amplified from
      genomic DNA by vectorette polymerase chain reaction. In primer extension
      reactions and RNase protection assays, residues C (at position -91), T (-71) and
      G (-70) were found to serve as transcription initiation sites of the gene.
      Amplification products and sub-fragments thereof were ligated upstream of the
      reporter gene chloramphenicol acetyltransferase to test for promoter activity.
      Constructs were transiently transfected into a Chinese hamster ovary cell line
      which was shown to express endogenous C beta 2 mRNA. The genomic sequence
      upstream the C beta 2 cDNA does have promoter activity. The region from position 
      51 to -292 proved sufficient to drive efficient transcription of the reporter
      gene. The promoter is AT rich (68%), does not contain a TATA box within 50 bp
      upstream of the first initiation site and possesses putative binding sites for
      several transcription factors such as PEA-3 and a glucocorticoid receptor.

PMID- 8982257
TI  - Molecular cloning of a novel ADP-ribosylation factor (ARF) expressed in
      planarians.

PMID- 8982259
TI  - Molecular cloning and analysis of the 5'-flanking region of the rat PP1 alpha
      gene.
AB  - We have cloned an 8 kbp genomic fragment of 5'-flanking region of the gene
      encoding the catalytic subunit of rat protein phosphatase 1 alpha. Neither CAAT
      box nor TATA box was detected but a 300 bp high GC region containing nine Sp1
      transcription factor binding sites is present immediately upstream of the
      translation start site, demonstrating that PP1 alpha is a housekeeping gene.
      Luciferase reporter assay showed that transcription of PP1 alpha is controlled at
      the high GC region.

PMID- 8982260
TI  - Peptide nucleic acids directed to the promoter of the alpha-chain of the
      interleukin-2 receptor.
AB  - Two 10-mer oligopyrimidine peptide nucleic acids (PNAs) were designed to
      interfere with IL-2R alpha promoter expression by binding to the regulatory
      sequences overlapping SRF and NF-kappa B transcription factor sites. Specific
      complexes were formed on each target sequence, and clearly involved (1) Hoogsteen
      hydrogen bonds as shown by experiments in which the purine strand of a single or
      double-stranded target was substituted with 7-deazadeoxyguanosine, (2) P-loop
      formation on double-helical DNA as evidenced by susceptibility to a single-strand
      specific nuclease. When formed on a single-stranded DNA target, these highly
      stable complexes were responsible for efficient physical blockage of T7 DNA
      polymerase elongation on the template DNA containing the target oligopurine
      sequence. On a double-stranded target, these complexes only formed at low ionic
      strength and were slowly dissociated at physiological ionic strength (pH 6.5)
      with a t1/2 of 6.5-7 h. The salt-dependent instability of preformed complexes on
      a plasmid target was probably the critical factor responsible for their lack of
      significant sequence-specific effect on IL-2R alpha promoter activity inside
      living cells.

PMID- 8982261
TI  - Negative transcriptional regulation of the chicken Na+/K(+)-ATPase alpha 1
      subunit gene.
AB  - Although the Na+/K(+)-ATPase alpha 1-subunit gene is ubiquitously expressed in
      vertebrates, its level of expression varies among tissue and cell types. In spite
      of similar mRNA distribution in tissues of mammals and birds, the 5'-flanking
      regions of alpha 1-subunit genes exhibit remarkable diversity; i.e., the core
      promoter activity of the TATA-less chicken alpha 1 gene strongly depends upon
      multiple Sp1-based regulation (six Sp1 sites), whereas the promoter activity of
      the TATA-like rat alpha 1-subunit gene relies on the two Sp1 and additional
      positive regulatory factors. Further analysis of the regulatory regions of the
      Na+/K(+)-ATPase alpha 1-subunit genes revealed that the vertebrate alpha 1
      subunit genes may share common inhibitory mechanisms for subtle transcriptional
      regulation; the core promoter activities can be either enhanced or repressed
      depending on the availability of inhibitory factors. Two potential candidates for
      such inhibitory elements in both avian and mammalian Na+/K(+)-ATPase alpha 1
      subunit genes are (1) a newly identified element, GCCCTC, and (2) a GCF-binding
      sequence, NN[G/c]CG[G/c][G/c][G/c]CN, or its reverse complement. Gel retardation
      assays using the inhibitory region of the chicken gene and crude nuclear extracts
      from tissue-cultured chicken and mouse cells showed the existence of a set of
      proteins that bind to this region. The amounts of individual regulatory proteins
      in different cell types seem to vary, resulting in differential formation of
      DNA/protein complexes in different cell types. Thus, the regulation of Na+/K(+)
      ATPase alpha 1-subunit gene expression under different cellular environment as
      well as in different cell types can be achieved by a shared mechanism; modulation
      of the ratio of the abundance of individual inhibitory factors.

PMID- 8982262
TI  - Tissue distribution of three members of the murine protein disulfide isomerase
      (PDI) family.
AB  - The distribution of PDI, ERp61 and ERp72, members of the protein disulfide
      isomerase (PDI) family of endoplasmic reticulum (ER) proteins, was determined in
      various murine tissues. Relative amounts of mRNA were measured using a
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) method.
      Protein levels were determined from Western blots. In most tissues, protein
      levels paralleled the amount of mRNA for each PDI family member. The tissue
      distribution of the PDI and ERp72 mRNAs was similar, although ERp72 was not as
      abundant as PDI in the tissues. The tissue distribution of the ERp61 mRNA was
      significantly different from the two other family members. To help define
      potential hormonal or maturational differences in the regulation of expression of
      PDI family members, mRNA was measured in the frontal cortex, liver, pituitary
      gland and uterus at timed intervals during postnatal maturation. Except in the
      pituitary gland, the mRNA levels at 10 days and 22 days after birth were
      essentially identical to those in the adult. The ERp61 and ERp72 mRNAs were
      present at 2- to 3-fold higher levels in the pituitary glands of the 10- and 22
      day-old mice, than in the adult mice. In addition, the pituitary gland PDI mRNA
      was 2- to 3-fold higher in 10-day-old mice than in adults. In general, levels of
      PDI family members were higher in secretory tissues than in other tissues in both
      immature and adult mice.

PMID- 8982263
TI  - Apoptosis is associated with an increase in saturated fatty acid containing
      phospholipids in the neuronal cell line, HN2-5.
AB  - Two widely different paradigms of stress, hypoxia and nutrient deprivation, were
      observed to trigger apoptosis in a clonal neuronal (hippocampal) cell line (HN2
      5) as judged by DNA laddering analysis and chromatin condensation. Since
      according to its original definition, apoptosis is concomitant with a dramatic
      change in cell morphology, the composition of major phospholipids that determine
      morphological properties of cells was analyzed in this study. We observed a
      significant increase (10-20%) in the proportion of saturated fatty acid side
      chains only in phosphatidylethanolamine (PE), phosphatidylserine (PS) and
      phosphatidylinositol (PI) but not in phosphatidylcholine (PC). This increase was
      independent of the paradigm of stress used (hypoxia or nutrient deprivation) to
      initiate apoptosis. Since phospholipids constitute the fabric of both plasma
      membranes as well as the membranes surrounding the intracellular organelles such
      as the lysosomes, endoplasmic reticulum and the nuclei, such an apoptosis
      associated, selective change in phospholipid composition could cause a dramatic
      and overall change in membrane fluidity, thus producing the typical shrinking,
      deformation and porosity of both nuclear as well as plasma and lysosomal
      membranes as observed in apoptotic cells. Leakiness of lysosomal and nuclear
      membranes could cause diffusion of deoxyribonucleases into cell nuclei, thus
      resulting in the characteristic cleavage and laddering of chromosomal DNA which
      accompany apoptosis.

PMID- 8982264
TI  - Interaction of liposomes with human skin in vitro--the influence of lipid
      composition and structure.
AB  - Liposomes have been suggested as a vehicle for dermal and transdermal drug
      delivery, but the knowledge about the interaction between lipid vesicles and
      human skin is poor. Therefore, we visualized liposome penetration into the human
      skin by confocal laser scanning microscopy (CLSM) in vitro. Liposomes were
      prepared from phospholipids in different compositions and labeled with a
      fluorescent lipid bilayer marker, N-Rh-PE (L-alpha-phosphatidylethanolamine-N
      lissamine rhodamine B sulfonyl). Fluorescently labelled liposomes were not able
      to penetrate into the granular layers of epidermis. However, the fluorescence
      from liposome compositions containing DOPE (dioleylphosphatidyl ethanolamine) was
      able to penetrate deeper into the stratum corneum than that from liposomes
      without DOPE. Pretreatment of skin with unlabeled liposomes containing DOPE or
      lyso-phosphatidyl choline (lyso-PC) enhanced the subsequent penetration of the
      fluorescent markers, N-Rh-PE and sulforhodamine B into the skin, suggesting
      possible enhancer activity, while most liposomes did not show such enhancement.
      Resonance energy transfer (RET) and calcein release assay between stratum corneum
      lipid liposomes (SCLLs) and the phospholipid vesicles suggested that the
      liposomes containing DOPE may fuse or mix with skin lipids in vitro and loosen
      the SCLL bilayers, respectively. Among the factors not affecting stratum corneum
      penetration were: negative charge, cholesterol inclusion and acyl chain length of
      the phospholipids. In conclusion, fusogenicity of the liposome composition
      appears to be a prerequisite for the skin penetration.

PMID- 8982265
TI  - Effect of fumonisin B1 on phosphatidylethanolamine biosynthesis in Chinese
      hamster ovary cells.
AB  - Fumonisin B1 has been shown to inhibit dihydroceramide synthesis and elevate
      cellular sphinganine levels in several cultured cell lines. In Chinese hamster
      ovary (CHO)-K1 cells, 20 microM fumonisin B1 inhibited sphingomyelin synthesis by
      75% after 5 h, but stimulated [3H]serine incorporation into PtdEtn by 5- to 7
      fold. Fumonisin caused a 10-20% increase in [3H]serine labelling of PtdSer. While
      fumonisin (20 microM) caused sustained inhibition of sphingomyelin synthesis,
      PtdEtn labelling peaked at 7-fold above controls at 12 h and declined to 4-fold
      by 24 h. Fumonisin treatment for 12 h increased the in vitro activity of PtdSer
      synthase by 62% and inhibited PtdSer decarboxylase by 35%, suggesting that
      increased PtdEtn labelling by [3H]serine is not by this pathway. An ethanolamine
      'trap' experiment was performed to assess the contribution of phosphoethanolamine
      from sphinganine degradation for PtdEtn labelling. Stimulation of [3H]serine
      incorporation into PtdEtn by fumonisin could be reduced by 60% with the inclusion
      of 50 microM unlabelled ethanolamine in the culture medium. The ethanolamine
      mediated reduction in [3H]serine incorporation into PtdEtn was accompanied by 4
      fold increase in cellular [3H]phosphoethanolamine. In control cells labelled with
      [3H]serine, 50 microM ethanolamine did not cause [3H]phosphoethanolamine to
      accumulate. Consistent with elevated phosphoethanolamine production in fumonisin
      treated cells, [3H]ethanolamine incorporation into PtdEtn was inhibited by 75%
      after 12 h. The degradation of endogenous long-chain bases to phosphoethanolamine
      and entry into the CDP-ethanolamine pathway appears to be a major pathway for
      PtdEtn synthesis in fumonisin-treated CHO-K1 cells.

PMID- 8982266
TI  - Bilirubin sensitized photooxidation of human plasma low density lipoprotein.
AB  - Previous investigations have shown that the bile pigment bilirubin can act as
      peroxyl radicals scavenger and transition metals trap, but also as a peroxidant,
      to erythrocyte ghost membranes through 1O2-driven photooxidation. In the present
      study we examined the changes occurring in the lipoprotein particle following
      bilirubin-sensitized photooxidation of isolated plasma LDL. The oxidative stress
      resulted in increased TBA reactivity, diene formation, free cholesterol
      oxidation, apo B fragmentation and enhanced uptake of the modified particle by
      the mouse macrophage scavenger receptors as well as the decrease binding to the
      native B, E-receptor on fibroblasts. The marked increase in TBARS production in
      D2O-enriched medium and the inhibition of lipid peroxidation of azide is
      consistent with singlet oxygen involvement in the oxidation process. The apo B
      bound Cu2+ appears to become redox active during photooxidation since the
      presence of EDTA in the reaction mixture greatly reduced protein fragmentation.
      It was also found that BHT inhibited almost completely the lipid peroxidation, as
      determined by the TBA reaction but could not totally abolish the formation of 5
      alpha-hydroxycholesterol, which is the main product formed by the direct attack
      of 1O2 on cholesterol. The results of this work strongly suggest that, through
      photooxidation by light-activated bilirubin, the lipoprotein particle may be
      modified in the blood stream as well, besides being modified in the well known
      oxidation site within the arterial wall. Our findings provide the rationale for
      extending these studies to clinical investigations, which aim at developing
      strategies for minimizing damage to arterial tissue following phototherapy of
      hyperbilirubinemic newborns or cancer patients after systemic administration of
      photosensitizers.

PMID- 8982267
TI  - Studies on protective mechanisms of four components of green tea polyphenols
      against lipid peroxidation in synaptosomes.
AB  - The comparison of the protective effects of four components of "green tea
      polyphenols' (GTP) - (-)-epigallocatechin gallate, EGCG; (-)-epicatechin gallate,
      ECG; (-)epigallocatechin, EGC; and (-)epicatechin, EC - against iron-induced
      lipid peroxidation in synaptosomes showed that: (1) the inhibitory effects of
      those compounds on TBA reactive materials from lipid peroxidation decreased in
      the order of EGCG > ECG > EGC > EC; (2) the scavenging effects of those compounds
      on lipid free radicals produced by lipid peroxidation could be classified as
      follows: ECG > EGCG > EC > EGC. Furthermore, we investigated the iron-chelating
      activity and the free radical scavenging activity of those compounds as their
      protective mechanisms against lipid peroxidation in synaptosomes. As for the iron
      chelating activity, the ratio of EGC, EGCG, ECG or EC to iron(III) was 3:2, 2:1,
      2:1 and 3:1, respectively. The hydroxyl radical (HO) scavenging activity of those
      compounds was investigated in a photolysis of the H2O2 system. It was found that
      their ability to scavenge hydroxyl radicals decreased in the order of ECG > EC >
      EGCG >> EGC. It was also found that they could scavenge lipid free radicals in
      the lecithin/lipoxidase system and their scavenging activity was classified as
      follows: ECG > EGCG >> EGC > EC. Moreover, we found that their antioxidant active
      positions were different from each other and the stability of the semiquinone
      free radicals produced by those compounds in NaOH solution decreased in the order
      of EGCG > ECG >> EC. The results indicated that the ability of those compounds to
      protect synaptosomes from the damage of lipid peroxidation initiated by Fe2+/Fe3+
      was dependent not only on their iron-chelating activity and free-radical
      scavenging activity, but also on the stability of their semiquinone free
      radicals.

PMID- 8982268
TI  - Ascorbate promotes low density lipoprotein oxidation in the presence of ferritin.
AB  - Whilst catalytic iron has been implicated in the development of atherosclerosis
      by initiating low density lipoprotein (LDL) oxidation, the source of such iron
      remains uncertain. Here, we show that LDL oxidation in the presence of ferritin
      was stimulated by ascorbate (15-60 microM), whilst this effect was inhibited by
      the iron chelator desferrioxamine. Ascorbate also showed an antioxidant activity
      at high concentrations (125-250 microM). Our results suggest that the combination
      of ascorbate with ferritin may supply free iron for LDL oxidation in vivo.

PMID- 8982269
TI  - Inhibition of microbial lipases with stereoisomeric triradylglycerol analog
      phosphonates.
AB  - 1,2(2,3)-Diradylglycero O-(p-nitrophenyl) n-hexylphosphonates were synthesized,
      with the diradylglycerol moiety being di-O-octylglycerol, 1-O-hexadecyl-2-O
      pyrenedecanylglycerol, or 1-O-octyl-2-oleoyl-glycerol, and tested for their
      ability to inactivate lipases from Chromobacterium viscosum (CVL) and Rhizopus
      oryzae (ROL). The experimental data indicate the formation of stable, covalent
      1:1 enzyme-inhibitor adducts with the di-O-alkylglycero phosphonates. The
      differences in reactivity of diastereomeric phosphonates with opposite
      configuration at the glycerol backbone was less expressed with both enzymes
      tested as compared to the influence of the stereochemistry at the phosphorus.
      Both lipases exhibited the same preference for the chirality at the phosphorus
      that was independent from the absolute configuration at the glycerol backbone.
      However, with CVL and ROL the inhibitors with the active site serine-directed
      phosphonate linked at position sn-1 of the glycerol moiety reacted significantly
      faster than the corresponding sn-3 analogs, reflecting the sn-1 stereopreference
      of the enzymes towards triacylglycerol analogs with a sn-2 O-alkyl substituent.
      In contrast, the phosphonates based on the 1-O-octyl-2-oleoylglycerol did not
      significantly inactivate CVL. Unexpectedly, these substances were hydrolyzed in
      the presence of lipase.

PMID- 8982270
TI  - Association of lipid A disaccharide synthase with aerobic glycerol-3-phosphate
      dehydrogenase in extracts of Escherichia coli.
AB  - Variants of the Escherichia coli UDP-GlcNAc O-acyltransferase (LpxA) and of the
      lipid A disaccharide synthase (LpxB) containing affinity chromatography tags (C
      terminal histidine 8 [H8] tails) were constructed in order to investigate whether
      or not these enzymes interact with other E. coli proteins. These variants (LpxA
      H8 and LpxB-H8) had specific activities in vitro that were similar to wild-type
      enzymes. Crude extracts made from E. coli cells expressing LpxA-H8 or LpxB-H8
      were chromatographed over Ni(2+)-NTA-Agarose, and proteins purifying with the
      tagged proteins were identified by SDS-PAGE, followed by blotting and N-terminal
      microsequencing. At high levels of LpxB-H8 expression, two heat-shock proteins
      (DnaK and GroEL) were associated with the disaccharide synthase, but not with the
      acyltransferase. Another major protein recovered with LpxB-H8 (both at low and
      high levels of expression) was the aerobic glycerol-3-phosphate dehydrogenase
      (GlpD). The latter interaction was specific, since GlpD did not bind the affinity
      resin when the affinity tag was present on the UDP-GlcNAc O-acyltransferase (LpxA
      H8). Velocity centrifugation experiments indicated that both wild-type LpxB and
      GlpD sedimented together under some conditions, but these aggregates were smaller
      than and distinct from inner membranes. Our findings suggest a possible new
      mechanism by which the biosynthetic pathways for lipid A and glycerophospholipids
      may be coordinated.

PMID- 8982271
TI  - Sulfatide is expressed in both erythrocytes and platelets of bovine origin.
AB  - A novel sulfated glycosphingolipid containing a sulfated galactosyl residue was
      isolated from bovine erythrocyte ghosts, and purified to homogeneity by column
      chromatography on DEAE-Sephadex and silica beads. Structural characterization
      included compositional analyses, permethylation studies, proton nuclear magnetic
      resonance (NMR) spectroscopy, negative secondary ion mass spectrometry (SIMS),
      solvolysis and immunostaining on thin-layer chromatogram. As a result, the
      structure of this glycolipid is proposed as HSO3-Gal beta 1-1 Cer. The ceramide
      portion contained d18:1, d18:0 and t18:0, and the predominant fatty acid
      consisted of palmitate and palmitate with a hydroxy group, as deduced by both
      compositional analysis and negative SIMS mass spectrometry. The component of this
      glycosphingolipid probably originates from erythrocytes and platelets as
      indicated by the results of flow cytometry analysis using Sulph I monoclonal
      antibody. The yield of galactosyl sulfatide was about 0.37 mg/kg wet bovine
      erythrocyte membranes, about three times that of human kidney. Our results
      strongly suggest that galactosylceramide sulfate on erythroid cells may play an
      important biological role in cell to cell interaction and recognition.

PMID- 8982272
TI  - Progesterone triggers the rapid activation of phospholipase D in the amphibian
      oocyte plasma membrane when initiating the G2/M transition.
AB  - Previous reports indicate that, in the Rana pipiens oocyte, progesterone triggers
      a rapid rise in 1,2-diacylglycerol (DAG) derived from phosphatidylcholine (PC) in
      the plasma membranes. This DAG transient, which appears and is terminated within
      60-90 s, is derived both from a phospholipase which we assumed to be
      phospholipase C and from sphingomyelin (SM) synthase. We now find that
      progesterone stimulates PC and DAG turnover primarily via the phospholipase D
      (PLD) and phosphatidic acid phosphohydrolase (PAP) pathways as well as via the SM
      ceramide pathway. Rana oocytes were prelabeled with [3H]choline chloride under
      conditions in which about 70% is incorporated into PC of the plasma membrane of
      the intact oocyte or with [3H]lysoplatelet activating factor (1-O-octadecyl-sn
      glycero-3-phosphocholine, lysoPAF) which is selectively incorporated into plasma
      membrane PC. Progesterone induced the release of [3H]choline from intact oocytes
      into the medium within 60-90 s. This choline release was dose-dependent and was
      not inhibited by a putative PC-specific phospholipase C inhibitor, D609.
      Progesterone also induced a transient rise in [3H]lysoPAF-derived [3H]DAG within
      1-2 min followed by a rise in [3H]PA. In the presence of 20 mM ethanol,
      progesterone stimulated formation of [3H]lysoPAF-derived phosphatidylethanol,
      indicating progesterone activation of PC-specific PLD and concomitant formation
      of PA. A DGK inhibitor (D102) reduced the level of [3H]PA, produced a sustained
      rise in [3H]DAG and was a weak inducer of meiosis in oocytes not exposed to
      progesterone. A PA phosphohydrolase inhibitor (propranolol) elevated [3H]PA and
      completely inhibited the progesterone-induced rise in DAG. Progesterone thus acts
      at oocyte plasma membrane receptors to release PC-derived DAG via both SM
      synthase and PC-PLD. The duration of the DAG signal is regulated by the
      coordinate action of DGK and PAP.

PMID- 8982273
TI  - Airway epithelial cells produce stem cell factor.
AB  - Airway epithelial cells modulate the inflammatory response in asthmatic, allergic
      and fibrotic lung diseases through the secretion of cytokines that regulate the
      movement and activation of inflammatory cells. Mast cells play an important role
      in the pathogenesis of these lung diseases. In this study we report that normal
      airway epithelial cells express stem cell factor which is a critical mediator of
      mast cell growth and differentiation and that transforming growth factor-beta
      inhibits secretion of stem cell factor by airway epithelial cells.

PMID- 8982274
TI  - A rab11-like gene is developmentally regulated in ripening mango (Mangifera
      indica L.) fruit.
AB  - A full-length cDNA clone from mango (Mangifera indica L.) fruit has homology to
      the rab11/YPT3 class of small GTPases. The corresponding mRNA is expressed in
      fruit, only during ripening. The likely involvement of this RabX protein in
      trafficking cell-wall modifying enzymes through the trans-Golgi network is
      discussed.

PMID- 8982275
TI  - How do protein kinases recognize their substrates?

PMID- 8982276
TI  - Interleukin-4 blocks the release of collagen fragments from bovine nasal
      cartilage treated with cytokines.
AB  - Interleukin-1 (IL-1) in combination with other cytokines can induce a
      reproducible release of collagen fragments from bovine nasal cartilage in
      culture. Over 70% of the total collagen is released by day 14 and this release is
      accompanied by the appearance of collagenolytic activity in the medium that
      cleaves collagen specifically at the one quarter/three quarter position.
      Interleukin-4 is able to prevent the release of collagen fragments from the
      tissue and this is accompanied by a reduced secretion and activation of
      collagenase (MMP-1) with an increase in tissue inhibitor of metalloproteinases-1
      (TIMP-1). IL-4, especially in the presence of IL-1, increased TIMP secretion by
      bovine nasal cartilage in culture. These results suggest that IL-4 is able to
      specifically block cartilage collagen resorption by down-regulating the
      production of collagenase (MMP-1) and up-regulating TIMP-1 by chondrocytes within
      the cartilage.

PMID- 8982277
TI  - A site of interaction between pleckstrin's PH domains and G beta gamma.
AB  - Pleckstrin is a 40 kDa substrate for protein kinase C found in platelets and
      neutrophils. Based upon its sequence, pleckstrin contains two of the recently
      described PH domains that are thought to be binding motifs for phosphatidyl 4,5
      bisphosphate (PIP2) and/or G protein beta gamma heterodimers (G beta gamma). In
      the present studies we have examined the interaction between pleckstrin and G
      beta gamma by incubating pleckstrin fusion proteins with lysates from human
      platelets. In this analysis, both the N-terminal and C-terminal PH domains from
      pleckstrin bound G beta gamma in vitro, as did peptides containing as little as
      the first 30 residues of the C-terminal pleckstrin PH domain. Introduction of a
      point mutation into this region, analogous to the mutation in the Btk PH domain
      that causes X-linked immunodeficiency disease (XID) in mice, dramatically
      disrupted this interaction. We propose that pleckstrin may interact with G beta
      gamma, and that one potential site for this interaction involves the first 30
      residues of pleckstrin's C-terminal PH domain.

PMID- 8982278
TI  - Modulation of degranulation and superoxide generation in human neutrophils by
      unsaturated fatty acids of odd carbon numbers.
AB  - Unsaturated fatty acids of odd carbons, 13:1(12), 17:1(10trans), 19:1(7) and
      19:1(10) inhibited release of myeloperoxidase (MPO) from fMet-Leu-Phe
      cytochalasin B-treated neutrophils. The inhibitory effect was smaller than that
      of aseanostatins which have been isolated as microbial-derived free fatty acids
      with a methyl blanch (i-14:0 and ai-15:0) (Journal of Antibiotics (1991) 44, 524
      532). These unsaturated fatty acids also inhibited lactoferrin release by the
      same treatment. On the other hand, 13:1(12), 15:1(10) and 19:1(10) inhibited fMet
      Leu-Phe-stimulated superoxide generation of neutrophils, and the fatty acids
      15:1(10), 17:(10) and 19:2(10,13) induced superoxide generation in both
      unstimulated cells and the cell-free system. However, none of unsaturated fatty
      acids of odd carbons tested inhibited beta-glucuronidase release, whereas
      15:1(10), 17:1(10), 19:1(10) and 19:2(10,13) rather enhanced an increase in beta
      glucuronidase activity liberated from cells at high concentrations over 35
      microM, indicating cellular damages by these fatty acids. These observations
      suggest that unsaturated free fatty acids having odd carbons such as 13, 15, 17
      and 19 may act as modulators of neutrophil functions including degranulation and
      superoxide generation.

PMID- 8982279
TI  - A major agonist-regulated capping activity in Dictyostelium is due to the capping
      protein, cap32/34.
AB  - Stimulation of starved Dictyostelium amoebae with the chemoattractant cAMP
      produces a rapid increase in actin nucleation activity at 5 seconds which is
      cotemporal with an increase in actin assembly and a decrease in Ca(2+)
      insensitive capping activity [1]. Further characterization of this capping
      activity, called aginactin, led to the isolation of an Hsc70 [2]. Here, we
      demonstrate that purified aginactin contains both Hsc70 and the heterodimeric
      barbed-end capping protein, cap32/34. Immunoprecipitation of cap32/34 from
      purified aginactin removes all capping activity while immunoprecipitation of
      Hsc70 does not, indicating that the capping activity of aginactin is an intrinsic
      property of cap32/34. Gel filtration and immunoprecipitation assays fail to
      demonstrate the existence of a stable, high affinity complex between Hsc70 and
      cap32/34 in either lysate supernatants or aginactin pools but indicate the
      presence of a transient, ATP-sensitive interaction in cell lysates.
      Reconstitution experiments with purified Hsc70 and cap32/34 demonstrate that
      Hsc70 neither stimulates nor inhibits the capping activity of native cap32/34.
      Furthermore, we measured a Kd of approx. 0.8 nM for the binding of cap32/34 to
      barbed ends of actin filaments in the absence or presence of Hsc70, in agreement
      with Kd values measured for purified capping protein from other sources. We
      conclude, therefore, that cap32/34 is responsible for the capping activity called
      aginactin and that Hsc70 is not a regulatory cofactor for cap32/34 in
      Dictyostelium but may function as a chaperone during assembly of the cap32/34
      heterodimer.

PMID- 8982280
TI  - Up-regulation of telomerase activity in human lymphocytes.
AB  - We detected telomerase activity in human lymphocytes obtained from normal donors.
      Telomerase was up-regulated within 24 h when peripheral blood mononuclear cells
      were cultured in the presence of phytohemagglutinin. The activity increased
      gradually over 72 h, then remained stable for 96 h. During this period, cell
      number and the length of telomeric DNA remained constant. Anti-CD3 monoclonal
      antibody and Pansolbin also induced telomerase activity. These results
      demonstrate that telomerase is regulated during lymphocyte activation as cells
      progress from G0 to S phase. This system is useful for the study of telomerase
      during carcinogenesis, and in the testing of telomerase-inhibitory drugs.

PMID- 8982281
TI  - Effect of introduction of an arginine16 in VIP, PACAP and secretin on ligand
      affinity for the receptors.
AB  - Rabbit secretin, which differs from all other mammalian secretins in having a Leu
      residue in position 6 (instead of Phe) and a basic residue (Arg) in position 16,
      had a lower affinity than porcine secretion on recombinant rat secretin receptors
      but had a greater affinity than porcine secretin on recombinant rat VIP1 and
      PACAP I receptors. Synthetic [L6] porcine secretin had a reduced potency on
      secretin and VIP1 receptors whereas [R16] porcine secretin had a similar binding
      profile as rabbit secretin. Thus, an arginine residue in position 16 reduced 3
      fold the affinity of secretin for secretin receptors but increased 30-fold its
      affinity for the VIP1 and PACAP I receptors. The introduction of an arginine
      residue in position 16, instead of glutamine, in VIP and PACAP had a similar
      effect: [R16] VIP and [R16] PACAP had 3- to 10-fold higher affinities than VIP
      and PACAP for VIP1 and PACAP I receptors, and 3-fold lower affinities for the
      secretin receptors. The three [R16] peptides also had a reduced potency on the
      chimeric receptor consisting of the N-terminal part of the secretin receptor
      grafted on the VIP1 receptor, and an enhanced potency on the chimeric receptor
      consisting of the N-terminal part of VIP1 receptor grafted on the secretin
      receptor, indicating that position 16 of each ligand interacted with the N
      terminal extracellular domain of the receptors.

PMID- 8982282
TI  - Nucleoside and nucleobase transport systems of mammalian cells.

PMID- 8982283
TI  - Lateral pressure in membranes.

PMID- 8982285
TI  - The localization of gangliosides in neurons of the central nervous system: the
      use of anti-ganglioside antibodies.

PMID- 8982286
TI  - Proteins involved in peroxisome biogenesis and functioning.

PMID- 8982284
TI  - Adaptation mechanisms of microorganisms to the toxic effects of organic solvents
      on membranes.

PMID- 8982287
TI  - Structure and function of proteins in G-protein-coupled signal transfer.

PMID- 8982288
TI  - "Benign erythrocytosis" and other familial and congenital polycythemias.
AB  - The term familial and congenital polycythemia encompasses a heterogeneous group
      of disorders with the common characteristic of an absolute increased red cell
      mass since birth and/or similar phenotype also present in relatives. In the last
      2 decades the differential diagnosis between primary and secondary familial
      polycythemias became more physiologically relevant as new sensitive techniques,
      such as accurate measurements of serum erythropoietin (S-EPO) concentration by
      radioimmunoassay (RIA) or ELISA, and assessment of growth of erythroid progenitor
      cells in vitro became available. Consequently, correct classification of many
      older previous reports of familial polycythemias is difficult. While familial
      secondary polycythemias due to high oxygen affinity hemoglobin mutants are not
      infrequent and have been well delineated in terms of molecular pathophysiology
      and phenotype during the last 3 decades, those secondary familial polycythemias
      due to 2,3 DPG deficiency are very rare. Familial and congenital polycythemias
      with increased EPO concentration and normal arterial oxygen saturation and oxygen
      dissociation kinetics represent an intriguing group of disorders wherein the
      molecular lesions remain obscure; however, in some instances a possibility of
      abnormal oxygen sensing pathway involving hypoxia inducible factor-1 (HIF-1) open
      an intriguing yet unexplored area of hematology and biology. In contrast the
      primary familial and congenital polycythemia (PFCP) has been only recently
      recognized (the first report published in 1977). Various designations have been
      used in the past to describe PFCP, a rare clinical syndrome, including: benign
      familial erythrocytosis, polycythemia vera of childhood, primary polycythemia,
      pure erythrocytosis, etc. Some of these terms stressed the relatively benign, non
      progressive course of the disease with a normal lifespan of affected subjects;
      however, the apparent benignity of some of these disorders has been questioned.
      These disorders are familial and/or congenital, and the clinical and laboratory
      evidence of secondary polycythemias must be excluded. Only about 2 dozen familial
      and sporadic cases with PFCP have been reported. However, the mutations of
      erythropoietin receptor (EPOR) found in some of families with PFCP represent the
      only defined molecular defect of primary polycythemic phenotypes. All reported
      PFCP associated EPOR mutations result in truncation of its intracytoplasmic C
      terminal domain which negatively regulates the EPO/EPOR signal transduction
      pathway. Subjects with these mutations have decreased or normal S-EPO and
      increased sensitivity of erythroid progenitor cells to low EPO concentrations in
      in vitro assays. Mutations of other genes involved in post EPOR signaling pathway
      such as JAK-2, HCP and STAT 5 may also play a causative role in pathogenesis of
      some of PFCP families where mutation of EPOR was not found.

PMID- 8982289
TI  - Peripheral blood progenitor cell (PBPC) transplantation with a single apheresis
      in patients with lymphoma, myeloma and solid tumors.
AB  - The aim of this study was to investigate if a single apheresis after peripheral
      blood progenitor cell (PBPC) mobilization can be used to rescue patients
      receiving high dose chemotherapy (HD.CHE) as treatment for an underlying
      malignancy. Eighteen consecutive patients who were admitted to the transplant
      unit for treatment were leukapheresed following mobilization with one of the
      following protocols: group I: rHuG-CSF alone, group II: conventional chemotherapy
      (C.CHE) + rHuG-CSF or rHuGM-CSF and group III: high dose cytoxan (HD.CTX) + rHuG
      CSF. The optimal day for leukapheresis was determined by following white blood
      cell counts (WBC), mononuclear cell counts (MNC) and CD34+ cell counts daily.
      Granulocyte-macrophage colony-forming cells (GM-CFC) assay was performed at the
      leukapheresis product and prior to reinfusion. All patients proceeded directly to
      ablative therapy according to their underlying malignancy. PBPC from single
      apheresis were reinfused to all patients and cytokines started 24 h after
      infusion. Hematologic recovery after HD.CHE was the parameter used to ensure
      successful engraftment. We have been able to recover adequate number of PBPC for
      transplantation with a single apheresis in all patients. The number of infused
      cells were for groups I, II and III: (1) median number of MNC 4.7, 3.58 and 2.79
      x 10(8)/kg, respectively (2); median number of CD34+ cells 4.4, 2.8, 2.7 x
      10(6)/kg, respectively. The median apheresis day was 6, 16 and 16, respectively.
      Recovery times to granulocyte count > 0.5 x 10(9)/ L was 9 d (range 9-12) and to
      platelets > 20 x 10(9)/L was 12 d (range 1-135); 17/18 patients have engrafted
      successfully independent of the mobilization method used. These data suggest that
      sufficient PBPC can be harvested at a single leukapheresis for hemopoietic rescue
      after myeloablative therapy. Rapid hematologic recovery occurs when cytokines
      alone after conventional or HD.CHE are used for mobilization. Results of
      collection products and hematopoietic recovery are independent of the
      mobilization technique used.

PMID- 8982290
TI  - Gene transduction into murine primitive hematopoietic cells with 2-gene
      retroviral vectors using a Transwell coculture system.
AB  - The present study aims at expressing a reporter gene in hematopoietic cells in
      vivo by introducing it into primitive hematopoietic cells with a 2-gene
      retroviral vector. Various constructs of retroviral vectors containing the human
      IL-2 receptor alpha chain gene (TAC) as the reporter and the neomycin
      phosphotransferase gene (neo) as a selectable marker were engineered, and the
      effectiveness of these vectors for expression of the reporter gene was evaluated
      after transfection into the packaging cell line GP + E86. It was found that the
      highest levels of reporter gene expression were attained with constructs ordered
      5' long terminal repeat (LTR)-TAC-internal promoter-neo-3' LTR. In experiments
      investigating the expression of a reporter gene in hematopoietic cells, we used
      the Escherichia coli beta-galactosidase gene (lacZ) instead of TAC, because a
      very sensitive detection method was available for lacZ. For transduction of
      hematopoietic progenitors, packaging cell lines producing recombinant viruses
      were cultured in a Transwell hung into a Dexter-type bone marrow (BM) culture.
      The BM cells were selected with G418, and transferred into irradiated recipient
      mice. LacZ enzyme activity was detectable in the peripheral blood lymphocytes
      (PBL) of recipients taken 8 wk after reconstitution.

PMID- 8982291
TI  - An assessment of the clinicohematological criteria for the accelerated phase of
      chronic myeloid leukemia.
AB  - In order to assess the relative importance of the clinicohematological features
      most commonly associated with the accelerated phase (AP) of chronic myeloid
      leukemia (CML) in 175 consecutive patients, 12 variables generally considered as
      indicating AP were analyzed for their predictive value for blast crisis (BC)
      appearance in less than 1 yr. At the time of analysis, 118 patients had died and
      104 had developed BC. At univariate study, 6 features were associated with a
      significantly higher BC-probability: poor performance status (ECOG score > or =
      2), unexplained fever/sweats, severe bone pain, progressive splenomegaly despite
      adequate therapy, blood basophils (> or = 20%) and peripheral blasts (6-12%). At
      logistic regression, only bone pain and blood blasts (6-12%) retained their
      prognostic importance; the relative risk of unexplained fever/sweats and
      progressive splenomegaly was also clinically relevant. One-year BC-probability
      from the appearance of 1 or more of the above features was 77.3% (95% CI: 66
      86.6) and 100% since all 4 were observed. Finally, at least 1 of the 4 features
      was present prior to death in 6 of 7 patients dying from CML-related causes while
      not in BC. AP can be defined by the appearance along CML evolution of 1 or more
      of the 4 above-mentioned clinicohematological features.

PMID- 8982292
TI  - The bone-marrow infiltration pattern in B-cell chronic lymphocytic leukemia is
      not an important prognostic factor. Danish CLL Study Group.
AB  - In a multicentre study of 635 consecutive newly diagnosed patients with B-CLL,
      the histological bone marrow (BM) specimens were reviewed independently by each
      of 3 pathologists and found evaluable for BM infiltration pattern in 575
      patients, 404 of whom had a CD5+, mainly FMC7-, faint surface-membrane
      immunoglobulin (SIg) fluorescence-intensity ppenotype. In these 404 patients the
      following BM infiltration patterns were found: mixed nodular-interstitial (30%),
      moderate interstitial (44%), heavy interstitial (20%) and diffuse packed (6%). In
      univariate survival analysis, significant differences were found according to BM
      pattern (p < 0.05), the presence of nodules being a favorable prognostic sign. In
      multivariate survival analysis in a model including age, clinical stage, BM
      pattern, BM lymphocytosis, WBC and sex, only age and stage but not BM pattern or
      BM lymphocytosis had independent prognostic significance. In stage A, progression
      free survival was significantly longer in patients with nodular than in patients
      with non-nodular bone-marrow pattern. The overall survival of these patients,
      however, did not differ, possibly owing to the prompt and prolonged treatment
      given to most patients at the time of progression to stage B or C. We conclude
      that in CD5+, SIg(faint), mainly FMC7-B-CLL, bone-marrow histology may predict
      unstable disease in early clinical stage but is not important for treatment
      decisions, when these are based on clinical stage.

PMID- 8982293
TI  - All-trans retinoic acid and in vitro cytokine production by acute promyelocytic
      leukemia cells.
AB  - Leukemic cells spontaneously secrete cytokines involved in the proliferation of
      the clone; in this study we evaluated the effects of all-trans retinoic acid
      (ATRA) on the in vitro autocrine production of cytokines by acute myeloid
      leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20
      ANLL of other cytotypes than APL) were studied; the in vitro secretions of IL-1
      alpha, IL-3, IL-4, IL-6, IL-10, G-CSF, GM-CSF, TNF-alpha were tested with and
      without ATRA addition. After 5 d exposure to ATRA 10(-6) M APL-treated samples
      showed a significant reduction of IL-6 (p = 0.008) and GM-CSF (p = 0.03) and a
      significant increase of IL-1 alpha (p = 0.01) production, if compared to
      untreated APL samples. No difference was seen in IL-3, IL-10 and IL-4
      productions; G-CSF production resulted absent in all but 3 APL cases, in which
      addition of ATRA determined increase in the production. Interestingly, the 3 G
      CSF-producing cases did not obtain clinical remission with ATRA; GM-CSF and IL-6
      were spontaneously produced by all the cases, and 7 of 10 APL patients
      subsequently obtained complete remission after induction. TNF-alpha was produced
      only in 1 case. No statistical difference was seen in all the productions
      obtained from other than promyelocytic acute leukemic cells, both with and
      without ATRA addition. However, it is noteworthy that the production of IL-6 was
      more than twice as high in ANLL non-APL than in APL cases. In conclusion, these
      data could thus suggest possible complementary mechanisms of the exhaustion of
      the leukemic clone upon treatment with ATRA.

PMID- 8982294
TI  - Transfusion of platelet concentrates--clinical evaluation of two preparations.
AB  - The aim of this study was to compare the clinical effect of transfusion of
      platelet concentrates (PC) prepared from pooled buffy coats (BC) and PCs
      collected from a single donor (SD) by an apheresis technique. The influence of
      storage time and various clinical conditions was also studied. Thirty-two
      patients suffering from haematological malignancies were given a total of 326
      platelet concentrates; 180 BC-PCs and 146 SD-PCs, median 7 transfusions per
      patient. BC-PCs contained 312 +/- 52 x 10(9) and SD-PCs 383 +/- 133 x 10(9)
      platelets/unit (mean +/- SD). The mean storage time of BC-PC was 3 d and that of
      SD-PC 1 d. The mean platelet count of the patients before transfusion was 11 +/-
      8 x 10(9)/L. Regression analysis showed a significant decrease of the post
      transfusion platelet corrected count increment (CCI) during storage of PCs for 1
      5 d (BC-PC: p < 0.01; SD-PC: p < 0.05). There was no difference in platelet
      increment between BC-PC and SD-PC. Human leukocyte antigen (HLA) alloimmunization
      was the major cause of clinical refractoriness to random donor platelet
      transfusions but splenomegaly also caused low CCI values.

PMID- 8982295
TI  - NK cell-mediated killing of AML blasts: role of histamine, monocytes and reactive
      oxygen metabolites.
AB  - Blasts recovered from patients with acute myelogenous leukaemia (AML) were lysed
      by heterologous natural killer (NK) cells treated with NK cell-activating
      cytokines such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha). The
      cytokine-induced killing of AML blasts was inhibited by monocytes, recovered from
      peripheral blood by counterflow centrifugal elutriation. Histamine, at
      concentrations exceeding 0.1 microM, abrogated the monocyte-induced inhibition of
      NK cells; thereby, histamine and IL-2 or histamine and IFN-alpha synergistically
      induced NK cell-mediated destruction of AML blasts. The effect of histamine was
      completely blocked by the histamine H2-receptor (H2R) antagonist ranitidine but
      not by its chemical control AH20399AA. Catalase, a scavenger of reactive oxygen
      metabolites (ROM), reversed the monocyte-induced inhibition of NK cell-mediated
      killing of blast cells, indicating that the inhibitory signal was mediated by
      products of the respiratory burst of monocytes. It is concluded that (i)
      monocytes inhibit anti-leukemic properties of NK cells, (ii) the inhibition is
      conveyed by monocyte-derived ROM, and (iii) histamine reverses the inhibitory
      signal and, thereby, synergizes with NK cell-activating cytokines to induce
      killing of AML blasts.

PMID- 8982296
TI  - Salvage chemotherapy for relapsed or refractory non-Hodgkin's lymphoma with a
      combination of ACES (high-dose Ara C, carboplatin, etoposide and steroids)
      therapy.
AB  - ACES (Ara-C, carboplatin, etoposide, steroids) therapy using granulocyte-colony
      stimulating factor (G-CSF) was designed for relapsed or refractory non-Hodgkin's
      lymphoma (NHL), and the therapeutic effects and adverse reactions were studied.
      The subjects were 40 patients, including 19 relapsed cases and 21 refractory
      cases, subjected to chemotherapy using anthracycline type agents. The ACES
      therapy consisted of carboplatin at 100 mg/m2 and etoposide at 80 mg/m2 for 4 d
      from the first day, Ara-C at 2 g/m2 on the fifth day, solumedrol at 500 mg for 5
      d from the first day and G-CSF at 2 micrograms/kg from the seventh day. This
      therapy was performed every 3 weeks, in principle. The doses were reduced to 70%
      of the above values for patients aged 70 yr or older. Among the 40 patients,
      complete remission (CR) was achieved in 14 (35%) and partial remission (PR) in 14
      (35%) for a response of 70%. The 50% survival period was 526 d, and the 2-yr
      disease-free survival rate was 58.3%. Adverse reactions of grade 3 or higher
      included granulocytopenia in 62.5%, anemia in 17.5% and thrombocytopenia in 50%,
      but there was no death related to treatment. Four patients underwent
      transplantation of hematopoietic stem cells and have survived for long periods.
      This treatment was effective against relapsed NHL and could be performed safely
      with few adverse reactions.

PMID- 8982297
TI  - Pulmonary fibrosis with megakaryocyte infiltration in agnogenic myeloid
      metaplasia with thrombocytosis.

PMID- 8982298
TI  - Increased ratio of thromboxane B2 and 6-keto PGF1 alpha in patients of hepatic
      venous outflow obstruction.

PMID- 8982299
TI  - Acquired and transient factor X deficiency associated with sodium valproate
      treatment.

PMID- 8982300
TI  - A low serum beta 2-microglobulin level despite bulky tumor is a characteristic
      feature of primary mediastinal (thymic) large B-cell lymphoma: implications for
      serologic staging.

PMID- 8982301
TI  - [The outlook for home care--from the standpoint of Doctors' association].

PMID- 8982302
TI  - [Narcotics control to support appropriate use of morphine for pain alleviation].

PMID- 8982303
TI  - [What terminal cancer patients seek from nurses in treatment at home].
AB  - We have provided care at home for 29 patients who were terminally ill, and from
      the fact that 3 of them needed excretion care, we learned something important for
      successful nursing care. The first necessity is the technical skill and knowledge
      of nursing care for the terminal cancer patients. We need to be able to provide
      guidance for the patient or family. The second is prompt consultation anytime
      when the patient or family needs it. The key to success is to create a medical
      network system for terminal cancer patients. The third is to provide support for
      the patient and family so that they pass the time without pain and meaningfully.

PMID- 8982304
TI  - [The present state of the 24-hour care system of our hospital and the examination
      of the significance and problems of the system].
AB  - The wishes of patients with terminal cancer are often not realized even if they
      indicate they want to die at home. We introduced a 24-hour visiting care system
      from November, 1994, with a view to making it possible for the patient who wants
      to to stay at home. As a result, the rate of the death at home increased; thus,
      the 24-hour visiting care system was significant for terminal care at home. On
      the other hand, from the viewpoint of a medical institution, the lack of
      sufficient cooperation with doctors and the increase of the burden on the staff
      were pointed out as problems to be resolved.

PMID- 8982305
TI  - [Home care that meets the wishes of patients with terminal stage cancer and their
      families].
AB  - As our ward is a general surgical ward, we formerly had difficulties providing
      appropriate care for patients with terminal cancer. To solve the problem, we have
      formed a nursing study group in order to provide home care that would meet the
      wishes of such patients and their families. Our specific approach was as follows:
      1) preparation of a form on which patient information is collected; 2) a support
      system for home care (such as pain control and home parenteral nutrition; and 3)
      a solid collaboration system between ward nurses and visiting nurses. Such a
      program enables us to understand the wishes of patients and families and to
      provide various support where needed. The project helps to lessen the anxiety and
      the burden that patients and families feel in home care, and improve the quality
      of life (QOL).

PMID- 8982306
TI  - [Assistance to enhance the use of home helper services for the cancer patient].
AB  - For the end-stage cancer patient to live at home with his or her quality of life
      (QOL) sustained, Home Helper Services are considered effective. In fact, however,
      many do not avail themselves of such services. Since the disease situation is apt
      to change dramatically, it is difficult to predict the length of time of care at
      home, and the patient's family does not tend to utilize such services unless the
      patient is completely bedridden. Short-term use or the difficulty or rapid
      response of such services has been among the reasons given of this. Given this
      background, there appears to be a need for suitable assessment in dealing quickly
      with possible disabilities which might occur and a number of occupations. Also,
      when considering home medical care for the cancer patient, an administrative
      system capable of a rapid response when problems of this kind occur is
      indispensable. Working on the administration to fulfill this need is also the
      task of the professionals in this field.

PMID- 8982307
TI  - [Attempt to create a HPN database].
AB  - We experienced fifty cases of HPN (home parenteral nutrition) from January 1987
      to May 1994. Using effectively these important data, we attempted to make a
      database for these fifty cases of HPN. We constructed a database based on Windows
      3.1-J and Access 2.0-J produced by Microsoft company. At this time, we introduce
      a part of the database, which must be completed in terms of input items and
      simplicity.

PMID- 8982308
TI  - [Enteral alimentation at home: why PEG now?].
AB  - The history of percutaneous endoscopic gastrostomy (PEG) is relatively short. In
      1980, a report entitled "Gastrostomy without laparotomy: A percutaneous
      endoscopic technique" by Ponsky and Gaudere was first published in the Journal of
      Pediatric Surgery. Thereafter, PEG soon saw widespread use in Western countries
      because of its clinical efficacy and economy. It has been performed in about
      170,000 cases annually in the US. In contrast, its spread in Japan has been
      extremely slow: only about 10,000 cases have undergone this procedure annually,
      and this number accounted for less than 5% of patients receiving enteral
      alimentation. The reason why PEG has not spread may be the medical insurance
      system in Japan and the local distaste for operation scarring. However, in
      consideration of the unprecedented ageing of society that is surely coming in the
      near future, the role of PEG in Japan must be reexamined. In this report, we
      presented the methodology of enteral alimentation at home by means of PEG, giving
      special consideration to: (1) "What points are improved by using enteral
      alimentation at home by means of PEG in various diseases; (2) dysphagia due to
      cerebral angiopathy; (3) terminal cancer; (4) otolaryngological diseases; and (5)
      Crohn disease. We also discussed "Why PEG is important now?" in performing
      enteral alimentation at home.

PMID- 8982309
TI  - [Trial of home anti-cancer chemotherapy with infusion of 5-FU and low-dose
      cisplatin].
AB  - We tried home anti-cancer chemotherapy for patients with advanced or recurrent
      cancer of the digestive system, using two disposable balloon pumps connected to
      an implantable drug delivery system via central venous line. There were 33
      patients under 75 years old, including 20 cases of gastric cancer, 9 cases of
      colorectal cancer, 2 cases of cholangiocarcinoma and 2 cases of esophageal cancer
      enrolled in this study. The protocol was combined chemotherapy with continuous
      intravenous infusion of 5-FU (300 mg/body/day) and low-dose intravenous injection
      of cisplatin (5 mg/body/day) in 10-day courses for two weeks, and it was repeated
      3 times for 6 weeks. Because of side effects such as nausea, vomiting and bone
      marrow suppression, treatment was discontinued in 12 cases with peritoneal cancer
      infiltration. In two of 10 with estimable disease, the reduction of the
      metastatic lymph node was observed, but no effect was shown in the colorectal
      metastatic liver tumor. Thanks to the portability of the pump with this method,
      the patient need not undergo hospitalization. Moreover, there is no renal
      dysfunction or other major side effects, quality of life is not compromised and a
      return to family and social life is possible. Thus, if the patient cannot take
      the oral nutrition, it is easy to start home hyper-alimentation.

PMID- 8982310
TI  - [Clinical study of home hepatic arterial infusion chemotherapy for liver
      metastasis from colorectal cancer].
AB  - The clinical response and QOL were examined with 16 outpatients treated with home
      hepatic arterial infusion chemotherapy for liver metastasis from colorectal
      cancer. Fluorouracil 1,000 mg/body/week was administered by 5-hour intra-arterial
      infusion with a portable disposable pump. Six out of 8 who replied to a
      questionnaire survey led a their usual life during the treatment, and the average
      hospitalization period was only 7 days (including mortal cases). The clinical
      response was evaluated with 13 patients; 3 prophylactic treatment cases were
      excluded from the original 16 cases. The number of partial responses and no
      change were 3 and 7, respectively, and the overall response rate was 23.1%. These
      studies suggest that home hepatic arterial infusion chemotherapy is beneficial
      for patients with liver metastasis by improving their QOL.

PMID- 8982311
TI  - [Questionnaire survey of families who lost a member regarding the home care
      received--mostly of families whose member had terminal cancer].
AB  - We conducted a questionnaire survey of 14 families who each had lost a member
      regarding the home care they received. Thirteen of the families surveyed had a
      member who had suffered from terminal cancer. This was thus a survey of "Home
      Care of Terminal Cancer Patients." In home care for patients with terminal
      cancer, one should realize they do not have much time, so to improve the balance
      of supply and demand, we urgently need to build a better system of cooperation
      with public officials to provide aggressive and prompt home care simulating
      welfare service.

PMID- 8982312
TI  - [Visiting nurse support for patients wishing to die at home].
AB  - Thirty-two (1994) and 55 (1995) patients in the terminal stage of many kinds of
      cancer were cared for satisfactorily at home by a visiting team of nurses from
      Niigata Cancer Center Hospital. A prostate cancer patient with multiple bone
      metastasis was suffering from morphine-resistant intractable pain, and highly
      dependent on medical care. We continued to take care of him by frequent
      visitation and psychological assist until he eventually died at home according to
      his wishes. It is important to create a suitable support team for the continual
      difficult home care of each terminal patient.

PMID- 8982313
TI  - [Factors promoting acceptance of death at home].
AB  - We have provided home treatment mainly for cancer patients since June 1995 and
      had 7 such patients until March 1996. Among them two patients died not at home
      but in the hospital, although the patients and their family understood that the
      patients were in the terminal stage of illness. It home was thought to be
      difficult that they accept death at their homes. From the standpoint of physical
      and mental conditions, social status and actual medical care, the factors to
      promote death at home were examined. The two cases mentioned above and their
      families wished to have treatment at home. The reasons why we decided to
      discontinue medical care at their homes were twofold: 1) the difficulty of
      palliating patients' symptoms and anxiety; and 2) the uneasiness of the family in
      caring for patients at home. Therefore sufficient palliation of symptoms and
      "death education" for patients and families are required to encourage death at
      home.

PMID- 8982314
TI  - [The possibilities and problems of a home setting hospice service for a patient
      living alone].
AB  - We provided home care service for a patient in the terminal stage of lung cancer.
      This patient had some difficulties, such as living by himself, having little
      financial means, and unable to use welfare programs because of the age
      restrictions of certain institutions. We, however, arranged the home care the
      patient wanted by carefully making contact with the health and welfare
      institutions involved. Through this case, we reported the possibilities and
      problems of a home setting hospice service for a patient living alone.

PMID- 8982315
TI  - [Suitable measure for medicines resulting from pharmacist-visit and assistance
      for a good treatment].
AB  - Our medication team, consists doctors, nurses, pharmacists, and other staffs,
      made an effort to satisfy our patients with medical treatment. We especially
      tried to guarantee patient rights. Pharmacists visited patients in September
      1995, seeking to inform every patient about effects and side effects of medicines
      using the "Medicine Information Sheet" with samples. As a result, in one case now
      under treatment by medicine, he no longer needs it. Then, our medication team had
      a conference and his doctor changed his prescription. In another case, we found a
      symptom suspected to be a side effect of a medicine. We asked his doctor about
      it, and he stopped the medicine in question. His medical condition then became
      better. This resulted in a "suitable amount" of medicine. We are confident that
      this is also necessary for every patient under treatment at home, when a
      pharmacist visits his or her home and informs them about the effects and side
      effects of medicines, and assists them to assure good treatment.

PMID- 8982316
TI  - [What can we do for cancer patients with pain to go home].
AB  - When patients suffering from cancer pain wish to stay at home, the most important
      condition is to relieve the cancer pain. But it is not enough; decreasing the
      fear of pain is another important problem. From these viewpoints, we have tried
      to assist these patients to go home. In this paper we report two cases of 61-year
      old and 57-year-old women with severe leg pain caused by pelvic recurrence of
      cancer of the uterus and rectum. At first, we needed high doses of morphine by
      intravenous administration all day long. To control their mental condition, we
      talked personally with them to understand their distress and asked them to put in
      writing anything about their anxiety in a special notebook. After that, we
      advised them on how to use anodyne, how to deal with side effects of the drugs
      and how to use various social services in their home. Then, after their cancer
      pain was controlled by radiotherapy and appropriate anodyne, they overcame their
      anxiety and at last they could go home.

PMID- 8982317
TI  - [Home terminal care for lung cancer--subcutaneous injection with morphine
      hydrochloride for cancer related pain from metastatic bone cancer in a terminal
      lung cancer patient].
AB  - Home management for cancer-related pain in a terminal cancer patient is usually
      performed by oral or intrarectal administration with analgesics. If such
      treatment fails to reduce cancer-related pain, we have to treat them with
      epidural, intravenous or subcutaneous injection of these agents in some cases. We
      encountered a terminal lung cancer patient with metastatic bone cancer who was
      treated with continuous subcutaneous injection of morphine hydrochloride at home.
      As a result, the patient's quality of life has been remarkably improved. The
      management of cancer-related pain with analgesics and terminal care at home are
      discussed.

PMID- 8982319
TI  - [How to palliate the symptoms of terminally ill patients at home].
AB  - We reported the kind of symptoms and how they could be palliated in terminally
      ill patients at home based on our experience of about 9 years. Cancer pain, which
      was the most frequent symptom, appeared in 67 among 126 patients receiving home
      care, and it could be effectively controlled with morphine; no patient returned
      to the hospital because of aggravation of pain. Very few patients stayed in the
      hospital and never returned home due to uncontrollable pain. Home parenteral
      infusion was done for 63 patients who were unable to eat or drink because of
      peritonitis carcinomatosa or cancer cachexia. High fever in the tumor mass was
      controlled by glucocorticoid hormone, and ascites was drained continuously when
      the patients suffered from abdominal distension. From analysis of the cases in
      which home care was interrupted or those in which patients were unable to
      transfer to home care, symptoms that were difficult to palliate at home were
      nausea caused by bowel obstruction, acute symptoms (bleeding, disturbance of
      consciousness, and so on), and dyspnea. But if the patients and family are eager
      for home care and an adequate medical support system is in place, home care may
      be possible despite these symptoms.

PMID- 8982320
TI  - [Trial of home infusion therapy for near-terminal stage patients with lung
      cancer].
AB  - To improve the quality of life in patients with malignant diseases at the near
      terminal stage, we established a system for home infusion therapy (HIT) in Osaka
      Prefectural Habikino Hospital in 1994. Thirty-three patients were taken care of
      at home using the HIT system from January, 1995 to May, 1996. Their average age
      was 70 years old. The duration of HIT varied from 1 to 105 days (mean:25.5 days).
      Twenty-four cases received parenteral nutrition. The others received agents for
      brain edema (4 cases), morphine hydrochloride (2 cases), and anti-fungal agents
      (3 case). Additionally, 63% of these patients required home oxygen therapy (HOT)
      with HIT. Questionnaires to their families revealed that they were afraid of the
      progress of the disease in patients and their physical burden became heavier
      after the start of HIT. However, they were quite satisfied with the results of
      HIT.

PMID- 8982318
TI  - [Effectiveness of Ge-132 to relieve pain and smooth home care administration for
      the terminal cancer patient].
AB  - Measures to alleviate pain are the most important issue in care of the cancer
      patient. In the present study, we investigated whether the use of narcotics could
      be reduced in the use of Ge-132 (Repargermanium) when used alone or together with
      a narcotic as a means to facilitate pain management in home care. The patients
      have died at home over the past 2 years with various types of cancer under our
      hospital supervision. Five were cases of bone metastasis, 6 of ascites. All cases
      had been given Ge-132, 750 approximately 2,500 mg/day (mean 1,000 mg) either
      orally or by IV. For pain control the first choice was MS Contin, and when the
      need arose the route used was intravenous or by suppository. We investigated the
      rate of narcotic usage and the dosage of same. Narcotics were used in 7 of the 16
      patients (44%) who died at home, and the daily dose was 20 approximately 240 mg
      (mean 60 mg). By using Ge-132 as a pain killer the rate of narcotics use and the
      dosage were decreased, resulting in less side effects from the narcotics. Thus,
      Ge-132 proved effective in relieving the pain of the terminal cancer patient
      receiving home care, and since it has no side effects it assures smooth home
      treatment.

PMID- 8982321
TI  - [Importance of oral and dental care in home medical care].
AB  - Recently, the importance of home medical care has been stressed. But patients,
      those assisting them and home care nurses do not attach much importance to oral
      and dental care in home medical care. When we visit patients who have asked for
      dental treatment through home care nurses, they appeared to have very poor oral
      hygiene; cavities were uncared for, dental plaque and dental calculus built up,
      and they used ill-fitting dentures. Through home dental care visits, it was not
      just the dental treatment but advice on dental hygiene management and diet that
      helped patients regain their appetite and bring back a smile to their face, while
      giving a rhythm to their life. This created a certain human feeling and brought
      about better patient quality of life (QOL), while at the same time helping to
      improve the QOL of the family as well.

PMID- 8982323
TI  - Mass screening for prostate cancer. The Swedish Council on Technology Assessment
      in Health Care.

PMID- 8982322
TI  - [Psychosocial support to improve quality of life (QOL) in home terminal carcinoma
      patients].
AB  - There are numerous psychosocial problems with home care for terminal cancer
      patients. We studied one case from the viewpoint of providing support for cancer
      patients and their families. Psychosocial problems are important for the life of
      cancer patients and their families. The cancer diagnosis and the terminal stage
      have different levels of psychosocial concerns. We must consider effective
      intervention with such psychosocial support. (1) The team delivery of health care
      in oncology is more crucial than ever. (2) Social work plays a key role. (3) We
      should strive to understand the roles of other members of teams. (4) Members of a
      support team should take turns in providing care according to the psychosocial
      conditions of the patients. (5) Sympathy and a broad social outlook are required
      of medical staff members.

PMID- 8982333
TI  - EI-1511-3, -5 and EI-1625-2, novel interleukin-1 beta converting enzyme
      inhibitors produced by Streptomyces sp. E-1511 and E-1625. I. Taxonomy of
      producing strain, fermentation and isolation.
AB  - EI-1511-3, -5 and EI-1625-2, novel interleukin-1 beta converting enzyme (ICE)
      inhibitors, were isolated from the culture broths of Streptomyces sp. E-1511 and
      E-1625. EI-1511-3, -5 and EI-1625-2 selectively inhibited the recombinant human
      ICE activity with IC50 values of 0.09, 0.38 and 0.2 microM, respectively.
      Taxonomy, fermentation of the producing strain and isolation of EI-1511-3, -5 and
      EI-1625-2 are described.

PMID- 8982334
TI  - EI-1511-3, -5 and EI-1625-2, novel interleukin-1 beta converting enzyme
      inhibitors produced by Streptomyces sp. E-1511 and E-1625. II. Structure
      determination.
AB  - The structures of three novel interleukin-1 beta converting enzyme inhibitors, EI
      1511-3, -5 and EI-1625-2 were determined by spectroscopic methods. Their absolute
      configurations were also determined by analyses of the CD spectra of the
      inhibitors and their oxidation products with chromium trioxide.

PMID- 8982335
TI  - EI-1511-3, -5 and EI-1625-2, novel interleukin-1 beta converting enzyme
      inhibitors produced by Streptomyces sp. E-1511 and E-1625. III. Biochemical
      properties of EI-1511-3, -5 and EI-1625-2.
AB  - EI-1511-3, -5 and EI-1625-2, novel interleukin-1 beta converting enzyme (ICE)
      inhibitors from the culture broths of Streptomyces sp. selectively inhibited the
      recombinant human ICE activity with IC50 values of 0.09, 0.38 and 0.2 microM,
      respectively, without inhibiting elastase and cathepsin B. Manumycin G, ent
      alisamycin, U-56,407, and manumycin A and B isolated simultaneously from the same
      strains also inhibited ICE. EI-1511-3, -5 and EI-1625-2 also inhibited mature
      interleukin-1 beta secretion from THP-1 cells with IC50 values of 5.4, 3.6 and
      2.2 microM, respectively. In this article, biological properties of EI-1511-3, -5
      and EI-1625-2 and, in addition, properties of manumycin-related compound are
      described.

PMID- 8982336
TI  - Madindoline, a novel inhibitor of IL-6 activity from Streptomyces sp. K93-0711.
      I. Taxonomy, fermentation, isolation and biological activities.
AB  - Selective growth inhibition against IL-6-dependent cells was detected in
      fermentation extracts of a microbial strain, K93-0711, which was characterized as
      Streptomyces species. Active metabolite, termed madindoline A and B, were
      isolated, and the structure was determined to be 3a-hydroxy-indoline with
      diketocyclopentene at the N position. Madindoline A and B displayed dose
      dependent inhibition of MH60 cells, an IL-6-dependent cell line, in presence of
      0.1 U/ml IL-6. The IC50 for madindoline A and B against this cell line was 8
      microM and 30 microM, respectively. These compounds did not inhibit the growth of
      cell lines which are not IL-6 dependent and the growth inhibition of the MH60
      cell line was reversed by addition of excess, 0.4 U/ml, of IL-6 to the culture
      media. These compounds did not show any antimicrobial activity at a concentration
      of 1,000 micrograms/ml.

PMID- 8982337
TI  - Sparoxomycins A1 and A2, new inducers of the flat reversion of NRK cells
      transformed by temperature sensitive Rous sarcoma virus. I. Taxonomy of the
      producing organism, fermentation and biological activity.
AB  - Streptomyces sparsogenes SN-2325 isolated from a soil sample collected in
      Hokkaido, was found to produce sparoxomycins A1 and A2, new modulators of
      proliferation of mammalian cells. Sparoxomycins A1 and A2 reverse the morphology
      of temperature-sensitive mutant Rous sarcoma virus-infected NRK cells (src(ts)
      NRK cells) from the transformed phenotype to the normal phenotype at the
      permissive temperature.

PMID- 8982338
TI  - Maltophilin: a new antifungal compound produced by Stenotrophomonas maltophilia
      R3089.
AB  - Strains of Stenotrophomonas maltophilia R3089, isolated from the rhizosphere of
      rape plants (Brassica napus L.), produced a novel antifungal compound, named
      maltophilin, which inhibited the growth of various saprophytic, human-pathogenic
      and phytopathogenic fungi but was inactive against Gram-positive and Gram
      negative bacteria. Maltophilin is a novel macrocyclic lactam antibiotic with a
      molecular mass of 510 mu. The compound was isolated from the culture filtrate by
      ethyl acetate extraction and gel filtration on Sephadex LH20 and purified by
      preparative HPLC on reversed phase. The structure of maltophilin was elucidated
      by electrospray mass spectrometry and 1H and 13C NMR spectroscopy.

PMID- 8982339
TI  - Exophilin A, a new antibiotic from a marine microorganism Exophiala pisciphila.
AB  - Exophilin A, a new antibacterial compound, was discovered in the culture of the
      marine microorganism Exophiala pisciphila NI10102, which was isolated from a
      marine sponge Mycale adhaerens. The absolute chemical structure of exophilin A
      was elucidated as a trimer of (3R,5R)-3,5-dihydroxydecanoic acid by spectroscopic
      methods and analyses of a degradative product. Exophilin A showed antimicrobial
      activity against Gram-positive bacteria.

PMID- 8982340
TI  - Microbial glycosylation of macrolide antibiotics by Streptomyces hygroscopicus
      ATCC 31080 and distribution of a macrolide glycosyl transferase in several
      Streptomyces strains.
AB  - In the course of our microbial transformation study on erythromycin derivatives,
      Streptomyces hygroscopicus ATCC 31080, which produces a polyether antibiotic
      carriomycin, was found to transform erythromycin derivatives to their inactivated
      derivatives. The structures of inactivated derivatives prepared by enzyme
      reaction using the cell extract, UDP-glucose (or UDP-galactose) and Mg2+ (or
      Mn2+) were elucidated on the basis of analysis of thei spectral data to be the
      compounds glycosylated at C-2' of a desosamine moiety, indicating that the enzyme
      is a macrolide glycosyl transferase (MGT). The MGT activity of cell extract from
      S. antibioticus ATCC 11891, a producing organism of oleandomycin, could be
      distinguished from that of ATCC 31080, based on the ability to glycosylate
      tylosin. We examined 32 actinomycete strains producing such polyketides as
      macrolide and polyether antibiotics, and found that 15 strains of Streptomyces
      have macrolide glycosyl transferase activity. It suggests that the MGTs have been
      distributed among at least polyketide producing Streptomyces strains.

PMID- 8982341
TI  - Novel blockade of cell surface expression of virus glycoproteins by leucinostatin
      A.
AB  - The nonapeptide leucinostatin A (LSA) inhibited syncytium formation without
      profoundly affecting HN glycoprotein synthesis in Newcastle disease virus (NDV)
      infected BHK cells. At similar doses of LSA, cytopathic effect and infectious
      virus production were suppressed in vesicular stomatitis virus (VSV)-infected BHK
      cells. Blockade by LSA of cell surface expression of NDV-HN and VSV-G
      glycoproteins was demonstrated, accompanied by intracellular accumulation of
      these virus glycoproteins. LSA acts as an inhibitor of mitochondrial F-type H(+)
      translocating ATPase, a key enzyme in the generation of ATP, but its action
      against cell surface expression of virus glycoproteins was independent of the
      depletion of intracellular ATP. LSA also acts as an ionophore, but its action on
      intoxication by ricin and diphtheria toxin was different from that of monensin.
      This novel action of LSA is expected to be useful in investigation of the
      mechanism of intracellular trafficking of proteins.

PMID- 8982342
TI  - Detection of tet(K) and tet(M) in Staphylococcus aureus of Asian countries by the
      polymerase chain reaction.
AB  - This study describes the use of the polymerase chain reaction (PCR) to detect the
      tet(K) and tet(M) tetracycline resistance genes in Staphylococcus aureus. Primers
      based on the DNA sequence of the tet(K) and tet(M) genes from S. aureus were used
      as primers in the PCR assay to detect the presence of genes for resistance to
      tetracycline and minocycline. Two-hundred and fifteen isolates of S. aureus from
      Asian countries as Japan, Indonesia, China, Korea and Thailand were examined, and
      the results confirm that tet(K) specifies resistance to tetracycline but not to
      minocycline and tet(M) specifies resistance to both tetracycline and minocycline.
      We observed two different types of clinical isolates of S. aureus strains
      resistant to minocycline and tetracycline: the first carried only the tet(M)
      gene, while the second carried both the tet(M) and the tet(K) genes. Almost all
      of the clinical isolates of S. aureus resistant to minocycline and tetracycline
      from Indonesia, China and Thailand carried both tet(M) and tet(K) genes, while
      most of clinical isolates of S. aureuss from Japan and Korea carried only tet(M)
      gene.

PMID- 8982344
TI  - Chemical modification and structure-activity relationships of pyripyropenes. 2.
      1,11-Cyclic analogs.
AB  - A series of 1,11-cyclic analogs of pyripyropene A were prepared. Replacement of
      the 1,11-acyl groups of pyripyropenes with 1,11-cyclic acetals effectively
      improved in vitro acyl CoA:cholesterol acyltransferase (ACAT) inhibitory
      activity. Especially noteworthy is benzylidene acetal analog 35, the most potent
      inhibitor (IC50 = 5.6 nM) among the derivatives prepared so far, which showed 16
      times more potent inhibitory activity than pyripyropene A.

PMID- 8982343
TI  - Chemical modification and structure-activity relationships of pyripyropenes. 1.
      Modification at the four hydroxyl groups.
AB  - Four hydroxyl groups of pyripyropenes have been modified and evaluated for their
      ability to inhibit microsomal acyl-CoA:cholesterol acyltransferase (ACAT)
      activity in vitro and to lower cholesterol absorption in vivo in a cholesterol
      fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory
      activity (IC50 = 13 nM) about 7 times better than pyripyropene A. Introduction of
      methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity
      (IC50 = 19 nM) and in vivo efficacy (ED50 = 10 mg/kg).

PMID- 8982345
TI  - A modification of the N-terminal amino acid in the eremomycin aglycone.
AB  - An Edman degradation of the antibiotic eremomycin aglycone produced the
      corresponding hexapeptide, which was aminoacylated with D-lysine, D-histidine or
      D-tryptophan derivatives to give new heptapeptide analogs of the eremomycin
      aglycone. The aminoacylation of the eremomycin aglycone produced an octapeptide
      analog. The substitution of D-lysine for the N-terminal N-methyl-D-leucine does
      not seriously affect the in vitro antibacterial properties of the eremomycin
      aglycone whereas the heptapeptides with the N-terminal D-tryptophan or D
      histidine moieties and the octapeptide with the N-terminal D-lysine are
      practically devoid of the antibacterial properties.

PMID- 8982346
TI  - Structure-activity relationships of cephalosporins having a
      (dimethylisoxazolidinio)vinyl moiety at their 3-position.
AB  - A series of cephalosporins having a (dimethylisoxazolidinio)vinyl group at their
      3-position were synthesized to investigate their structure-activity
      relationships. With regard to the olefin geometry, the (E)-vinyl compound
      exhibited higher in vitro activity than the (Z)-compound. Regarding the C-7
      substituents, the replacement of 2-aminothiazole with 5-amino-1,2,4-thiadiazole
      increased the anti-pseudomonal activity. Determination of the absolute
      configuration of the C-3 substituent is also presented. Among the compounds
      synthesized, we selected 7 beta-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2
      (fluoromethoxyimi no)acetamido]-3-[(E)-2-((S)-2,2-dimethyl-5-isoxazolidinio)vinyl
      ]-3-cephem-4-carboxylate (YM-40220), which showed well-balanced in vitro activity
      and an excellent in vivo efficacy against Staphylococcus aureus Smith, as a
      candidate for further development.

PMID- 8982348
TI  - Structure-activity relationship of 1 beta-methyl-carbapenem to its antibacterial
      activity: effect of the C-2 side chain and the 1 beta-methyl group.

PMID- 8982347
TI  - A novel neuronal cell protecting substance, naphthomycinol, produced by
      Streptomyces sp. PF7.

PMID- 8982349
TI  - Synthesis and biological activity of new cephem compounds with a 3-(2-butenyl)-
      and a 3-(1,3-butadienyl)group at their 3-position.

PMID- 8982351
TI  - Orbuticin, a new secondary metabolite from Acremonium butyri.

PMID- 8982350
TI  - Cycloaddition reactions of a 3-(1,3-butadienyl)cephalosporin and antibacterial
      activity of new cephem derivatives.

PMID- 8982352
TI  - Induction of antibodies against human prion proteins (PrP) by DNA-mediated
      immunization of PrP0/0 mice.
AB  - Prion diseases are neurodegenerative disorders, affecting humans and animals. The
      human diseases include kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann
      Straussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). To
      generate monospecific antisera against human prion proteins we have immunized
      mice with DNA coding for different human prion proteins. We constructed
      immunization vectors expressing individual genotypes of either the cellular prion
      gene (PRNP) or mutant forms under appropriate promoters. This approach avoids the
      preparation of infectious material for immunization. To circumvent immunological
      tolerance prion protein-deficient PrP0/0 mice were used for the DNA-mediated
      immunization. Thereby monospecific sera were raised capable of specifically
      precipitating in vitro synthesized human prion proteins. With prion protein
      specific peptide ELISAs, we found that antibodies are predominantly directed
      against the octapeptide repeat region and to a lesser extent to regions
      comprising the signal peptide, the neurotoxic domain or the GPI anchor. In
      contrast, prion gene-positive (PrP+/+) BALB/c mice immunized under the same
      experimental conditions as the PrP0/0 mice did not respond with antibody
      formation against the human prion protein. This is the first report clearly
      showing that immune competent prion protein-deficient mice react with a vigorous
      polyclonal immune response after DNA-mediated immunization with human prion gene
      sequences.

PMID- 8982353
TI  - Quantitation of the cytosolic phospholipase A2 (type IV) in isolated human
      peripheral blood eosinophils by sandwich-ELISA.
AB  - Sandwich enzyme-linked immunosorbent assay (sELISA) was developed for precise
      quantitation of cytosolic phospholipase A2 (cPLA2 type IV) concentration in
      isolated human peripheral blood eosinophils as an alternative to semiquantitative
      chemiluminescent assay employing immunoprecipitation/Western blot analysis. In
      this assay, monoclonal mouse anti-human cPLA2 antiserum was used as the capture
      antibody, polyclonal rabbit anti-human cPLA2 antiserum as the secondary antibody,
      and alkaline phosphatase-conjugated goat anti-rabbit IgG as the tertiary,
      reporter antibody. Purified human cPLA2 (0-1000 ng/ml) dissolved in Tris-HCl
      buffered saline was used as the standard protein. The detection limit for cPLA2
      in 10(6) eosinophils was 0.109 ng/ml, and coefficients of inter- and intra-assay
      variation were 4.23% and 7.07%, respectively. There was no cross-reactivity with
      other (secretory) isoforms of PLA2 (sPLA2 types I-III) either from porcine
      pancreas, human synovial fluid, or bee venom. In separate studies, the recovery
      of cPLA2 was > 83% when eosinophil lysate was supplemented exogenously with two
      different concentrations of cPLA2. From a total protein content of 22.3 +/- 1.7
      micrograms/10(6) cells, the baseline concentration of cPLA2 was 0.38 +/- 0.18
      ng/10(6) cells in eosinophils obtained from mildly atopic donors. Immunoblotting
      studies confirmed the complete specificity for the type IV isoform as detected by
      sELISA. This sELISA method permits the precise quantitative assessment of cPLA2
      in nanogram quantities per million cells, which has not previously been possible
      by immunoblotting analysis.

PMID- 8982354
TI  - Preferential labeling of alpha-amino N-terminal groups in peptides by biotin:
      application to the detection of specific anti-peptide antibodies by enzyme
      immunoassays.
AB  - Experimental conditions (pH 6.5, 24 h reaction, peptide:biotin ratio 1:5) were
      defined for preferential incorporation of the biotin molecule in the N-terminal
      alpha-amino group of peptides. This strategy could be helpful in numerous
      applications when an entire peptide chain must remain accessible for antibody or
      receptor binding. We illustrate this advantage in a solid-phase enzyme
      immunoassay designed to detect antibodies specific for bovine beta-lactoglobulin
      present in rabbit or human sera. This test involves synthetic peptides
      biotinylated in different positions and immobilized on a solid phase. The use of
      biotin/streptavidin interactions permitted more efficient detection of specific
      anti-peptide antibodies than solid phases prepared using conventional passive
      adsorption techniques. The highest levels of antibody binding were measured when
      biotinylation occurred at the N-terminal extremity of immobilized peptides.

PMID- 8982355
TI  - Quantitation of RT-PCR amplified cytokine mRNA by aequorin-based bioluminescence
      immunoassay.
AB  - We described here a bioluminescence-based immunoassay for the quantitation of RT
      PCR amplified cytokine mRNA. This technique uses a standard RT-PCR procedure,
      with the following modifications. The forward primer in the PCR reaction is
      labeled with a 5' biotin molecule. Following PCR, a digoxigenin-conjugated
      oligonucleotide probe is hybridized to the target biotin-labeled DNA template.
      The hybridized duplex is captured onto a streptavidin-coated microtiter plate.
      The bound product is quantitated by adding digoxigenin-specific antibodies
      conjugated with the photoprotein aequorin. The amount of specific DNA captured
      onto the plate is quantitated by triggering the bioluminescence reaction through
      the addition of calcium ions. This technique detected as low as 40 amol of
      amplified cytokine products, or 500 copies of templates when 27 PCR cycles were
      used. The high sensitivity of this technique enables the quantitation of target
      DNA during the exponential phase of the PCR reaction. The aequorin
      bioluminescence assay is an alterative non-radioactive method for the
      quantitation of PCR products.

PMID- 8982356
TI  - A comparison of efficacy and specificity of three NK depleting antibodies.
AB  - This study compares in vivo efficacy and specificity of the three NK cell
      depleting antibodies anti-asialo GM1, anti-NK 1.1 and the recently described TM
      beta 1, which is directed against the interleukin-2 receptor beta chain. All
      three antibodies are equally efficacious as assessed by abolishing NK mediated
      cytolytic activity induced by a high dose virus infection or Poly IC against YAC
      1 targets. Similarly, the generation of virus-specific cytotoxic T cells (CTL)
      was unimpaired after NK depletion in two different virus infections. However, if
      mice are treated with the antibodies several days after virus infection, when
      strong CTL responses have already been generated, anti-asialo GM1 and-to a lesser
      extent-also TM beta 1 have a significant effect on CTL activity. Only after
      treatment with anti-NK 1.1 antibody, CTL activity was not significantly impaired.
      We conclude, that of the NK depleting antibodies currently available, anti-NK 1.1
      allows the best differentiation of activated CTL and NK cells in vivo.

PMID- 8982357
TI  - On the masking of signals on immunoblots by cellular proteins.
AB  - When determining the concentration of a particular protein in a cell extract, or
      when comparing the amount of a protein in different samples, it is a common
      practice to use specific antibodies in immunoblotting to compare the samples side
      by side with known amounts of purified protein. Here we show that with many
      antibodies, in particular monoclonal antibodies, the sensitivity of detecting the
      cognate antigen on immunoblots can be significantly reduced when the antigen is
      in a mixture with other cellular proteins. The signals on the immunoblots are
      masked by other endogenous proteins in the cell lysate, making the amount of the
      protein on the immunoblot appear to be less than the actual amount, thus
      invalidating direct comparison with purified protein.

PMID- 8982358
TI  - Optimization of lymphocyte proliferation assay for cells with high spontaneous
      proliferation in vitro: CD4+ T cell proliferation in bovine leukemia virus
      infected animals with persistent lymphocytosis.
AB  - Evaluation of antigen specific lymphocyte proliferation is extremely difficult
      with cells displaying high spontaneous proliferation in vitro, such as bovine
      leukemia virus (BLV) and T cell leukemia virus type I (HTLV-I) infected cells. We
      introduced modifications to a standard proliferation protocol, and for the first
      time report antigen specific proliferation in BLV infected animals with
      persistent lymphocytosis (a benign proliferation of B lymphocytes). Serum
      (autologous, heterologous or fetal) but not medium was a major factor
      contributing to spontaneous proliferation. Spontaneous proliferation was strongly
      serum concentration dependent and reducing serum to 0.5-1% resulted in decreased
      background proliferation and development of a functional assay. Addition of
      indomethacin (3-6 micrograms/ml) further increased antigen specific responses not
      only from persistently lymphocytotic but also from lymphosarcoma animals. Thus,
      this modified proliferation protocol can be used in infections where background
      proliferation hinders evaluation of antigen-specific CD4+ T cells.

PMID- 8982359
TI  - Dissociation of monoclonal antibody-antigen complexes: implications for ELISA
      procedures.
AB  - A single step solid phase radioimmunoassay (SS-SPRIA) has been developed for
      human chorionic gonadotropin (hCG) using monoclonal antibodies (MAb) from culture
      media adsorbed immunochemically on plastic tubes. The assays have been found to
      be very simple in terms of operation and do not demand purification of MAbs.
      Several MAbs which do not show any displacement in liquid phase RIA and ELISA
      provide a satisfactory SS-SPRIA. Our investigations revealed that the assumption
      regarding the stability of the primary Mab-Ag complex during incubation and
      washing steps in ELISAs is not strictly valid for dissociable MAbs. A comparison
      of different assay systems suggests that the single step SPRIA offers additional
      advantages over conventionally used multistep ELISA procedures and provides a
      quantitative probe for the analysis of epitope-paratope interactions.

PMID- 8982360
TI  - Human antibodies responsible for binding inhibition and polymerization inhibition
      of human immunodeficiency virus type 1 reverse transcriptase.
AB  - Using a solid-phase non-radioisotopic (non-RI) reverse transcriptase (RT) assay,
      antibodies inhibiting human immunodeficiency virus type 1 (HIV-1) RT activity
      (RTI antibody) were investigated for their ability to inhibit binding of RT to a
      template-primer and DNA polymerization. The RTI antibody inhibited the binding of
      RT to the template-primer (BI antibody), and directly reacted with the RT
      template-primer complex and inhibited enzymatic activity (PI antibody). The RTI
      antibody interfered with formation of the RT-template-primer complex suggesting
      that it recognized the antigenic site involved in template-primer binding of RT
      molecules. Since deoxynucleotide triphosphates (dNTPs) blocked inhibition of the
      RT activity by the PI antibody, the antigenic site recognized by the PI antibody
      may be closely related to the dNTP binding site. The seropositivities of the BI
      and PI antibodies were 84.6% and 91.2%, respectively, in HIV-1-infected
      individuals; healthy individuals, HTLV-I-positive individuals, autoimmune disease
      patients and leukemia patients were all seronegative. No significant correlation
      of residual RT activities was observed when BI and PI antibodies were compared (r
      = 0.688). It is possible that the epitopes recognized by the BI antibody differs
      from those recognized by the PI antibody. The assays described are able to detect
      BI and PI antibodies in the sera of HIV-1-infected individuals.

PMID- 8982361
TI  - Enhanced specificity for small molecules in a convenient format which removes a
      limitation of competitive immunoassay.
AB  - Anti-complex immunoassay systems for small molecules permit the exquisite
      specificity achievable with monoclonal antibodies to be expressed to an extent
      which is not possible with competitive format immunoassay. While our previously
      reported anti-complex system is superior to competitive systems in terms of
      sensitivity, precision and specificity we have found that this specificity may be
      enhanced dramatically by simply interposing a wash step between the addition of
      sample and that of the labelled anti-complex antibody. When such a wash step was
      attempted with the competitive format system, after addition of sample but before
      addition of the labelled component, assay performance was degraded to the extent
      of making it unusable. We suggest, therefore, that the inherent flexibility of
      the anti-complex approach for small molecule assay creates an opportunity for
      remarkable enhancement of the functional specificity of primary antibody.

PMID- 8982362
TI  - A simple nested RT-PCR method for quantitation of the relative amounts of
      multiple cytokine mRNAs in small tissue samples.
AB  - It is difficult to quantitate cytokine mRNA profiles in small human tissue
      specimens obtained by a needle biopsy, even using standard RT-PCR methods,
      because the amount of mRNA in the specimens is very small. To address this
      problem, we developed highly sensitive, quantitative, nested RT-PCR techniques to
      evaluate the expression of multiple cytokine mRNAs in synovial specimens obtained
      by needle biopsy. To reduce effects of variation of initial RNA concentrations,
      cDNA from each target RNA sample was normalized, using a simplified competitive
      PCR method, to the levels of beta-actin cDNA. The first and the second (nested)
      PCR were performed in the same tube to prevent contamination. The number of PCR
      product bands, evident on polyacrylamide gel electrophoresis, was used to
      quantitate the relative amounts of target cDNA. Using our methods, it was
      possible to evaluate, in a single synovial tissue specimen obtained by needle
      biopsy, the relative amounts of mRNAs for 10 cytokines (TNF-alpha, IL-1 beta, IL
      2, IL-4, IL-6, IL-10, IL-12 p40, IL-13, IL-15, IFN-gamma) and CD3 delta chain.
      Our methods are particularly valuable if there are multiple target mRNAs,
      numerous samples, or if the amounts of mRNAs are limited. The methods are
      applicable to a wide variety of tissues and target mRNAs.

PMID- 8982363
TI  - MTS/PMS colorimetric assay is unsuitable for measuring mitogenic responses in
      porcine blood lymphocytes.

PMID- 8982364
TI  - Reconstruction after total gastrectomy: what is preferred technique?

PMID- 8982365
TI  - Calcification in colorectal hepatic metastases correlates with longer survival.
AB  - BACKGROUND: Calcification occurs in 12-27% of hepatic colorectal metastases, but
      its clinical significance and its influence on prognosis are unknown. METHODS:
      All patients diagnosed with colorectal liver metastases at the Ottawa Regional
      Cancer Center in 1991 (n = 97), as well as those enrolled in chemotherapy trials
      in 1990-1992 (n = 51), were entered into a retrospective cohort study. Thirty-six
      patients were excluded due to inadequate follow-up. In the remaining 112,
      abdominal CT scans and/or ultrasound examinations were used to determine the
      presence of calcification. Charts were reviewed for variables, including primary
      tumour pathology, amount of liver involvement by tumour (< 25%, 25-50%, > 50%),
      and the chemotherapeutic agents received, and were subjected to multivariate and
      regression analysis. End point was survival in months or to December 1993 (median
      follow up 24 months). RESULTS: Patients with calcification (n = 31) (28%) were
      compared to those who did not have calcifications (n = 81). The groups were
      comparable with respect to sex, age, time to calcification, time to metastases,
      and treatment type. Calcification occurred independent of the degree of tumour
      differentiation, the presence of mucinous adenocarcinoma, or the hepatic tumour
      burden. Nine patients with calcified metastases (30%) had calcification at
      presentation. Biopsies showed calcification next to viable tumour cells with an
      absence of an inflammatory reaction. Survival was improved with better primary
      tumour differentiation and less tumour burden. The presence of calcification had
      a statistically highly significant improvement in survival (P < 10(-6), relative
      risk = .19) independent of other variables. CONCLUSIONS: The presence of
      calcification within a colorectal liver metastasis appears to imply a
      significantly better prognosis.

PMID- 8982366
TI  - N-nitroso compounds in the gastric juice of normal controls, patients with
      partial gastrectomies, and gastric cancer patients.
AB  - BACKGROUND: It has been suggested that the variation of biochemical and
      microbiological parameters in the gastric juice may play a role in the
      development of gastric cancer. In the present study we concurrently assessed the
      presence of N-Nitroso compounds (NOC) and their precursors, bacteria and
      carcinoembryonic antigen (CEA) in the gastric juice of normal controls, patients
      with gastric resection, and advanced gastric cancer. METHODS: Detailed analyses
      of biochemical and microbiological parameters such as pH, nitrite (NO2)
      concentration, N-nitroso compounds (NOC) concentration, carcino-embryonic antigen
      (CEA) level, total viable counts (TVC), nitrate-reductase positive bacterial
      counts (NRPBC), and identification of micro-organisms were carried out. RESULTS:
      Significantly higher mean pH values, NO2, NOC and CEA concentrations, TVC, and
      NRPBC were found in partial gastrectomies compared with normal controls, and all
      these intragastric parameters were significantly higher in patients with gastric
      cancer than in those with partial gastrectomies. As far as surgical methods are
      concerned, higher mean pH values, NO2 and NOC concentrations, TVC, NRPBC, and
      anaerobic bacterial counts were observed in the juice of patients with Billroth
      II compared with Billroth I gastrectomies. Apart from the type of surgical
      reconstruction, higher mean NOC levels were recorded in patients with more severe
      histological changes and H. pylori infection. CONCLUSIONS: All these data suggest
      that the presence of high levels of NOC in the gastric juice of gastroresected
      patients can be considered a risk factor of gastric stump cancer.

PMID- 8982367
TI  - Immunosuppressive cytokines (IL-10, TGF-beta) genes expression in human gastric
      carcinoma tissues.
AB  - BACKGROUND: Contribution of immunosuppressive cytokines to tumor progression in
      many types of cancers has been suggested. To characterize the in vivo expression
      of immunosuppressive cytokines in gastric cancer, we analyzed the messenger RNA
      (mRNA) expression of transforming growth factor-beta (TGF-beta) and interleukin
      10 (IL-10) in human gastric carcinoma tissues. METHODS: Both tumor tissues and
      nontumor tissues from each resected specimen of 29 primary gastric carcinomas
      were tested for IL-10 and TGF-beta mRNA expression by the reverse transcriptase
      polymerase chain reaction (RT-PCR), and the mRNA expression was correlated with
      various pathological parameters of the tumors. RESULTS: Among the 29 tumors,
      mRNAs of TGF-beta and IL-10 were detected in 79% and 62% of tumor samples,
      respectively. These cytokines were detected only in 31% for TGF-beta and 17% for
      IL-10 in nontumor samples. Both mRNAs were frequently expressed in the poorly
      differentiated adenocarcinomas and the tumor tissues with high degree of stage or
      lymph node metastasis. CONCLUSIONS: Local expression of immunosuppressive
      cytokines may contribute to the progression of primary gastric carcinomas
      possibly through immunosuppression.

PMID- 8982368
TI  - Preoperative simultaneous cisplatin- or carboplatin-based chemotherapy and
      radiotherapy for squamous cell carcinoma of the oral cavity.
AB  - BACKGROUND: Encouraging results have been reported with cisplatin- or carboplatin
      based chemotherapy regimens and simultaneous irradiation treatment in advanced
      and unresectable head and neck head and neck cancer. We have therefore examined
      the effectiveness of such therapy on tumor control, survival, and toxicity in
      patients with advanced oral squamous cell carcinoma. METHODS: Forty-one patients
      with squamous cell carcinoma of the oral cavity (including soft palate) were
      treated preoperatively with cisplatin or carboplatin, and 5-fluorouracil or
      peplomycin in combination with simultaneous irradiation to a target volume of
      40Gy, and 2-6 weeks later, curative surgery was performed. RESULTS: Thirty-eight
      patients (91.7%) had Stage III or IV disease, and three patients had Stage II
      lesions. The preoperative clinical responses of the primary tumor were: 25
      patients (61.0%) achieved a complete response (CR), 15 (36.6%) a partial response
      (PR), only 1 patient (2.4%) had stable disease or no change (NC). The overall
      response rate was 97.6%. Histological effects according to the grading system of
      Shimosato and coworkers [Jpn J Clin Oncol 1:19-35, 1971] were seen in 38/41
      (92.7%). Of clinical CR patients, 73.9% were also histologic negative for tumor.
      Side effects of this therapy were relatively low and reversible. With a median
      follow-up of 52.8 months (range 17-92 months), 5-year cumulative survival rates
      were 81.5% for all patients, 100% for Stage II, 88.6% for Stage III, and 76.4%
      for Stage IV patients, respectively. There was no significant postoperative
      morbidity. CONCLUSIONS: This preoperative chemoradiotherapy regimen was highly
      active, well tolerated, and appeared to have a survival benefit even for advanced
      carcinomas of the oral cavity.

PMID- 8982369
TI  - Comparison of anastomotic suturing techniques in the rat trachea.
AB  - BACKGROUND: Tracheal resection is the preferred treatment for primary tracheal
      tumors. Anastomotic tension can be a problem, even when various tension-relieving
      release maneuvers are employed. Excessive tension can cause anastomotic sutures
      to pull through the tracheal tissue, with resultant early tracheal anastomotic
      dehiscence. To test the hypothesis that interrupted horizontal mattress sutures
      would withstand the forces of tension better than interrupted simple sutures, an
      experimental study of rat tracheal anastomoses was done. METHODS: Twenty rats
      were killed and their tracheas excised. The tracheas were divided in the mid
      portion and end to end anastomoses were done using interrupted 7-0 polypropylene
      sutures. Ten tracheas had anastomoses done with interrupted simple sutures, and
      10 had interrupted horizontal mattress suturing. RESULTS: Anastomotic breaking
      strength was 2.30 +/- 0.57 N for the interrupted simple sutured anastomoses and
      2.15 +/- 0.48 N for the interrupted horizontal mattress group (P = 0.54). The
      difference was not significant. CONCLUSIONS: In this animal study, interrupted
      simple and horizontal mattress suturing withstood the disruptive forces of
      anastomotic tension equally well.

PMID- 8982370
TI  - Histologic trends in thyroid cancer 1969-1993: a clinico-pathologic analysis of
      the relative proportion of anaplastic carcinoma of the thyroid.
AB  - BACKGROUND: It was observed that new presentations of anaplastic carcinoma of the
      thyroid had become infrequent in the last two decades. METHODS: All cases of
      thyroid cancer seen at our centre between 1969-1993 (n = 2921) were classified as
      papillary 49%, follicular 34%, medullary 7.5%, anaplastic 4.7%, and other 4.8%.
      The total number of thyroid cancers show a 3.5-fold rise. RESULTS: The
      differentiated thyroid cancers show a significant rising trend as against the
      relative proportion of anaplastic carcinoma, which shows a significant decline (P
      = 0.002). Clinicopathologic data on 124 patients of anaplastic carcinoma revealed
      50% patients had either long-standing goitres, previous thyroid abnormalities, or
      associated differentiated thyroid carcinoma on histology. CONCLUSIONS: The
      decline in the relative proportion of anaplastic carcinoma may in part be
      explained by the clinicopathologic findings or it may be attributed to
      histological reclassification.

PMID- 8982371
TI  - Cryoablation for carcinoma of the prostate.
AB  - Percutaneous transperineal cryoablation of the prostate is now available in the
      armamentarium for treatment of prostate cancer. Technical advances in real-time
      transrectal imaging of the prostate and improvements in cryosurgical equipment
      have brought this modality into the limelight of available prostate cancer
      management. Cryosurgery can be offered to many patients with prostate cancer.
      However, the main indications for its use include primary treatment for localized
      disease, salvage therapy after failure of traditional methods, and relief of
      local symptoms. A historical background, description of the technique, and
      clinical experience at several medical centers including the University of
      California San Diego, Allegheny General Hospital, University of Texas M.D.
      Anderson Cancer Center, and Crittenton Hospital, are presented.

PMID- 8982372
TI  - Tracheoesophageal fistula developing during chemotherapy for non-Hodgkins
      lymphoma.
AB  - Lymphoma is an unusual cause of tracheoesophageal fistula (TEF). Most fistulas
      develop after radiation therapy and are a rare occurrence in patients treated
      with chemotherapy alone. The presence of a TEF is usually indicative of active
      lymphoma. This report describes a tracheoesophageal fistula that developed during
      chemotherapy for diffuse large cell lymphoma.

PMID- 8982373
TI  - Spleen- and pancreas-preserving total gastrectomy with superextended
      lymphadenectomy including dissection of the para-aortic lymph nodes for gastric
      cancer.

PMID- 8982374
TI  - Management of soft tissue sarcomas of the extremity in adults.
AB  - Concepts of the current management of soft tissue sarcomas (STS) of the
      extremities in adults are presented. The role of surgery, radiation, and
      chemotherapy as well as the combination of these modalities are reviewed. The
      addition of radiation therapy to less than radical surgery has resulted in higher
      rates of limb preservation and acceptable local control. A multidisciplinary
      approach will help achieve optimal functional results with less morbidity.
      Treatment of systemic disease is poor with current methods. Innovative uses of
      existing systemic modalities or new modalities will be important to improve
      results in the management of these difficult tumors.

PMID- 8982377
TI  - Histology of intestinal Whipple's disease revisited. A study of 48 patients.
AB  - Whipple's disease is an infectious disorder with intestinal and extra-intestinal
      manifestations. We reinvestigated the intestinal histology in a series of 48
      patients (10 females, 38 males; mean age 56.5 years, standard deviation of the
      mean +/- 11.2 years). A total of 126 biopsy samples, obtained prior to, during,
      and after therapy, were evaluated by light microscopy. In 43 patients (90%),
      histology was consistent with common descriptions, while it was uncommon in 3
      patients (6%), and non-diagnostic in 2 patients (4%). During treatment, several
      alterations occurred. Apart from a continuous decrease in PAS-positive
      macrophages, the pattern of mucosal infiltration changed from diffuse to patchy.
      Moreover, the cytological aspects of PAS-positive macrophages changed
      substantially, and this change was used to propose four different subtypes.
      Initially, subtype 1 macrophages predominated (74%), but showed a gradual
      decrease within a few months of therapy. After 15 months, subtype 3 and subtype 4
      macrophages predominated (< 80%). In 7 of 9 patients followed over long periods
      some subtype 3 or subtype 4 macrophages persisted. It is concluded that at
      diagnosis and during treatment the intestinal histology of Whipple's disease is
      heterogeneous. A few PAS-positive macrophages commonly persist at long-term
      follow-up. This and other features suggest the presence of a persistent immune
      defect.

PMID- 8982376
TI  - Prognostic criteria in nonfunctioning pancreatic endocrine tumours.
AB  - To identify prognostic subgroups among non-functioning (nonsyndromic) pancreatic
      endocrine tumours, a series of 61 tumours were analysed systematically for
      macroscopic, histopathological and immunohistochemical variables potentially
      predictive of malignancy. High-grade nuclear atypia, elevated mitotic rate and
      multifocal necrosis allowed us to separate 5 poorly differentiated carcinomas
      from 56 well differentiated tumours. Among the latter, 29 well-differentiated
      carcinomas showing gross local invasion or metastases were identified. Vascular
      or perineural microinvasion, Ki67 proliferative index > 2%, mitotic rate > or =
      2, size > or = 4 cm, capsular penetration, nuclear atypia, lack of progesterone
      receptors and presence of calcitonin were among the variables correlated with
      malignancy. The first two were the most sensitive and specific. Their presence or
      absence was used in the 27 tumours lacking evidence of malignancy at the time of
      surgery to separate 11 cases with increased risk of malignancy (in 2 of which
      metastases developed during follow-up) from 16 cases with limited risk. The
      resulting four prognostic groups of non-functioning pancreatic endocrine tumours
      (limited- and increased-risk tumours, well-differentiated carcinomas and poorly
      differentiated carcinomas) showed distinct survival curves, which were
      significantly affected by vascular microinvasion, Ki67 proliferative index and
      metastases.

PMID- 8982378
TI  - Detection of Tn, sialosyl-Tn and T antigens in hereditary nonpolyposis colorectal
      cancer.
AB  - The simple mucin-type carbohydrate antigens Tn, sialosyl-Tn, T and the 'cryptic'
      sialylated variant of the last represent the mucin core oligosaccharide
      structures that are produced in the initial steps of the mucin biosynthetic
      pathway. Utilizing monoclonal antibodies anti-Tn antigen (HB-Tn1), anti-sialosyl
      Tn antigen (HB-STn1), anti-T antigen (HB-T1) and the biotinylated Amaranthus
      caudatus agglutinin (ACA), we have investigated the expression of the simple
      mucin-type carbohydrate antigens in hereditary nonpolyposis colorectal cancer
      (HNPCC; 15 cases) compared with sporadic colorectal cancer (CRC; 60 cases) and
      normal colonic mucosa (30 cases). A variable positivity of Tn, sialosyl-Tn, T and
      the cryptic sialylated form of this latter antigen was encountered in both HNPCC
      and sporadic CRC cases; in addition, in normal colonic mucosa a constant
      reactivity was encountered only for Tn and the cryptic sialylated form of T,
      while negative results were always obtained for sialosyl-Tn and T antigens.
      Statistical analysis, performed using a Chi-square test, showed significantly
      lower (P = 0.037) expression of sialosyl-Tn and higher (P = 0.022) expression of
      T in HNPCC than in sporadic CRC, suggesting a greater presence of beta 1,3
      galactosyltransferase activity in HNPCC than in sporadic CRC. We were unable to
      identify a peculiar phenotype for HNPCC with simultaneous evaluation of
      reactivity for HB-Tn1, HB-STn1, HB-T1 and ACA; the biological significance of the
      preferential expression of T antigen in HNPCC remains to be investigated.

PMID- 8982375
TI  - Molecular variants of fibronectin and laminin: structure, physiological
      occurrence and histopathological aspects.
AB  - This review deals with biological and pathological aspects of various isoforms of
      the matrix molecules fibronectin and laminin. They are generated by different
      molecular mechanisms: ED-A+ and ED-B+ fibronectin by alternative splicing of pre
      mRNA, de novo-glycosylated fibronectin by alternative post-translational O-linked
      glycosylation of the IIICS region, and the laminin isoforms by exchange of single
      chains of the heterotrimeric molecule. In contrast to the "common" fibronectin,
      the distribution of ED-B+ and de novo-glycosylated fibronectin is restricted to
      embryonic tissues; they subsequently reappear in granulation tissue, in fibrosing
      processes and in tumour stroma. The expression of these so-called oncofetal
      fibronectins is stimulated by growth factors (TGF beta). The association of the
      ED-B+ fibronectin with proliferative activity and newly formed vessels identifies
      this fibronectin variant as a marker of cellular activity in the process of
      fibrosis and as a suitable agent for the evaluation of tumour angioneogenesis.
      Initial results suggest a correlation between the amount of ED-B+ and de novo
      glycosylated fibronectin in tumour stroma and the behaviour of carcinomas with
      regard to their invasiveness and propensity for metastatic dissemination. The
      current nomenclature of the laminin molecule family is presented. The laminin
      chain constitution of basement membranes switches from embryonic or
      proliferatively active to adult terminally differentiated tissues [disappearance
      of the laminin beta 2 (s) chain] and depends on the tissue type. The discrepancy
      between the loss of basement membranes (multiple basement membrane defects) in
      carcinomas and the recently reported increased laminin chain synthesis in these
      tumours may be explained by abundant laminin chain deposition outside the
      basement membrane in the carcinoma invasion front, possibly associated with
      enhanced adhesion of budding tumour cells.

PMID- 8982380
TI  - Is the incidence of primary adenocarcinoma of the lung increasing?
AB  - Primary carcinoma of the bronchus is a major cause of death in males and females.
      Several studies report an increase in the incidence of adenocarcinoma and have
      suggested that this reflects changes in smoking habits or, alternatively, that it
      is a spurious rise due to changes in diagnostic criteria. To examine the latter
      suggestion we reviewed three cohorts of bronchial carcinoma from 1970, 1980 and
      1990, using immunocytochemical techniques to refine diagnosis. We found that
      squamous cell carcinoma had been consistently overdiagnosed and adenocarcinoma
      and adenosquamous carcinoma consistently underdiagnosed in all groups. Also, many
      tumours showed evidence of divergent differentiation with both squamous and
      glandular components present. There was a small, but real temporal increase in
      the proportion of adenocarcinoma over the 10 years between 1970 and 1980, but
      this was not sustained between 1980 and 1990.

PMID- 8982379
TI  - Detection and typing of hepatitis C RNA in liver biopsies and its relation to
      histopathology.
AB  - This paper describes the correlation of hepatitis C genotypes detected in liver
      tissue with histological grading (inflammatory activity) and staging (degree of
      fibrosis/cirrhosis). The viral genotype was analysed by type-specific polymerase
      chain reaction (PCR) and correlated with histology and age of patients. In 69
      patients with chronic hepatitis C (HCV) infection, genotypes 1a and 1b were
      detected in 13 (18.8%) and 31 (44.9%) liver biopsies, respectively. Genotypes 2a
      and 2b were each detected once (1.5%) and 12 (17.4%) tissue samples showed a
      mixed infection with two genotypes. In 11 (15.9%) biopsies, no genotype could be
      established. The liver specimens were grouped according to the presence or
      absence of genotype 1b: group A consisted of specimens infected with genotypes
      1a, 2a, and 2b (n = 16), Group B contained biopsies infected with genotype 1b (n
      = 42), and group C were biopsies with no detectable genotype (n = 11). Activity
      (grade) of chronic hepatitis was not different in these three groups. However,
      advanced fibrosis/cirrhosis was observed in 16 (38.1%) biopsies in group B
      (containing genotype 1b), compared with none in group A (P = 0.01). The mean age
      of patients in group B was significantly higher than that in group A (P = 0.038),
      and the mean age of patients with advanced fibrosis was higher than that of
      patients with low fibrosis scores within these two groups (P = 0.004). Stepwise
      logistic regression revealed an independent association of age and genotype 1b
      (group B) with advanced fibrosis/cirrhosis. These data indicate that patients
      infected with genotype 1b have an higher risk of developing cirrhosis than do
      patients with other genotypes.

PMID- 8982381
TI  - Expression of the PIP/GCDFP-15 gene and survival in breast cancer.
AB  - Expression of the PIP/GCDFP-15 gene was determined by measuring PIP/GCDFP-15-mRNA
      in breast carcinomas of 91 patients. The patients were followed-up for an average
      of 47 months after initial diagnosis and treatment of the disease. There were no
      deaths in the group of 14 patients with tumours of high PIP/GCDFP-15-mRNA levels,
      while 16 of 77 patients of the group with low PIP/GCDFP-15-mRNA tumour levels
      died. A similar advantage for high PIP/GCDFP-mRNA expression was observed with
      regard to disease free survival.

PMID- 8982382
TI  - A comparative immunohistochemical study of mammary and extramammary Paget's
      disease and superficial spreading melanoma, with particular emphasis on
      melanocytic markers.
AB  - A comparative immunohistochemical study was performed on Paget's disease of the
      nipple (PDN), extramammary Paget's disease (EMPD) and cutaneous superficial
      spreading melanoma (SSM) using antibodies to S100, NK1-C3 and HMB45, cytokeratin
      (CAM 5.2) and c-erb B2 oncoprotein (21N). Conventional histochemical stains for
      intracytoplasmic mucin and melanin were also done. Of the 20 cases of PDN,
      positivity was seen in 12 with S100, 16 with NK1-C3, none with HMB45, 20 with CAM
      5.2 and 19 with 21N. All 5 cases of EMPD were CAM 5.2 positive and HMB45, S100
      and 21N negative. Three EMPD were NK1-C3 positive. All 10 cases of SSM were S100,
      NK1-C3 and HMB45 positive and all were CAM5.2 and 21N negative. Mucin was
      demonstrable in 11 cases of PDN and all of EMPD but none of SSM. Melanin was seen
      in 2 PDN, 3 EMPD and all SSM cases. Identification of mucin and melanin,
      therefore, proved an unreliable means of distinguishing these diseases.
      Immunohistochemistry for cytokeratin and HMB45 appear to be the most specific
      markers in differentiating Paget's disease and SSM. Antibodies to c-erb B2 may
      also be valuable in this situation.

PMID- 8982383
TI  - Expression of adhesion molecules in primary B-cell gastric lymphoma and lymphoid
      follicles.
AB  - To determine whether primary B-cell gastric lymphoma (GL) is one entity, we
      examined the expression of three adhesion molecules in the microvasculature of
      lymphomas. Stromal cells, including vascular endothelial cells, within lymphoid
      follicies of the gastric mucosa were also investigated. Twenty-two surgical
      specimens of GL were classified into low-grade malignant lymphoma arising from
      mucosa-associated lymphoid tissue (low-grade lymphoma, n = 9), and high-grade
      malignant lymphoma with (secondary high-grade lymphoma, n = 6) or without
      (primary high-grade lymphoma, n = 7) a low-grade component. The proportion of
      venules positive for ELAM-1 or VCAM-1 was significantly higher (P < 0.001) in
      primary high-grade lymphoma than in low-grade and secondary high-grade lymphomas.
      In gastric lymphoid follicles, the stromal cells of the germinal centre (GC) were
      positive for ICAM-1, ELAM-1, and VCAM-1, but the stromal cells of the marginal
      zone (MZ) were positive only for ICAM-1. We found two patterns of adhesion
      molecule expression in gastric lymphoid follicles, the MZ pattern and the GC
      pattern. Low-grade and secondary high-grade lymphomas, which had the MZ pattern,
      might be of MZ-cell lineage, but most primary high-grade lymphomas, which had the
      GC pattern, might be of follicular centre cell lineage.

PMID- 8982384
TI  - Ultrastructural evidence for colocalization of kappa light chain- and beta 2
      microglobulin-derived amyloids using double labelling immunogold electron
      microscopy.
AB  - In systemic amyloidosis, it is essential to decide what type of amyloid protein
      is deposited in tissues before the therapy can be selected and the prognosis
      assessed in each patient. We examined tissues affected by amyloid deposition from
      a patient with multiple myeloma by immunohistochemistry and double labelling
      immunogold electron microscopy and demonstrated colocalization of kappa light
      chain- and beta 2-microglobulin-derived amyloids in the same tissue. beta 2
      Microglobulin-derived amyloid had ultrastructurally characteristic features that
      distinguished it from kappa light chain-derived amyloid. This is the first report
      of the colocalization of two different amyloids by immunoelectron microscopy.

PMID- 8982385
TI  - Bioenergetics of the archaebacterium Sulfolobus.
AB  - Archaea are forming one of the three kingdoms defining the universal phylogenetic
      tree of living organisms. Within itself this kingdom is heterogenous regarding
      the mechanisms for deriving energy from the environment for support of cellular
      functions. These comprise fermentative and chemolithotrophic pathways as well as
      light driven and respiratory energy conservation. Due to their extreme growth
      conditions access to the molecular machineries of energy transduction in archaea
      can be experimentally limited. Among the aerobic, extreme thermoacidophilic
      archaea, the genus Sulfolobus has been studied in greater detail than many others
      and provides a comprehensive picture of bioenergetics on the level of substrate
      metabolism, formation and utilization of high energy phosphate bonds, and primary
      energy conservation in respiratory electron transport. A number of novel
      metabolic reactions as well as unusual structures of respiratory enzyme complexes
      have been detected. Since their genomic organization and many other primary
      structures could be determined, these studies shed light on the evolution of
      various bioenergetic modules. It is the aim of this comprehensive review to bring
      the different aspects of Sulfolobus bioenergetics into focus as a representative
      example of, and point of comparison for closely related, aerobic archaea.

PMID- 8982386
TI  - Cloning and sequencing of novel genes from Vibrio alginolyticus that support the
      growth of K+ uptake-deficient mutant of Escherichia coli.
AB  - Novel genes that functionally complement the growth of K+ uptake-deficient mutant
      strain of Escherichia coli TK420 have been cloned from the marine bacterium
      Vibrio alginolyticus. The nucleotide sequence revealed three open reading frames.
      The second gene was homologous to proC gene and allowed the growth of proC
      defective mutant strain of E. coli chi 342 in the absence of proline. The first
      and third genes, but not proC, were required for the growth of TK420 in a
      synthetic medium containing 10 mM K+ and 100 mM Na+. Since K+ uptake activity of
      TK420 was restored by the introduction of these genes, these two genes were
      considered to be directly related to K+ transport. Homologous genes were found in
      E. coli, but their functions have not been reported.

PMID- 8982387
TI  - Kinetic analysis of hexose uptake in Saccharomyces cerevisiae cultivated in
      continuous culture.
AB  - As the expression of the hexose transporters in Saccharomyces cerevisiae is
      regulated by the external fructose concentration, in vivo fructose transport was
      investigated at a number of different but constant fructose concentrations in a
      continuous culture. The in vitro uptake rate and kinetic parameters were studied
      by uptake of 14C-labelled fructose. From Eadie-Hofstee plots, based on the
      results of the in vitro uptake experiment, K(m) and Vmax for the different steady
      state conditions were determined. These results demonstrate that as fructose
      concentrations increase, fructose consumption rates and K(m) increase and Vmax
      slightly decreases. However, remarkably a large discrepancy was observed between
      in vivo determined consumption rates in the continuous culture and the in vitro
      uptake rates from the 14C-labelled fructose uptake experiment on cells from an
      identical steady-state condition. In every condition the in vivo consumption rate
      was approx. 2-3 times higher than the in vitro uptake rate. A comparable
      discrepancy was observed for glucose uptake rates; however, in vivo and in vitro
      galactose uptake rates were identical. These observations imply that kinetic
      analyses of sugar transport mechanisms can only be performed correctly when
      accompanied by a comparison with in vivo determined consumption rates.

PMID- 8982389
TI  - Formate bound to cytochrome oxidase can be removed by cyanide and by reduction.
AB  - Using 14C-radiolabeled formate we have found that the rapid form of oxidized
      cytochrome oxidase can bind up to 1 mol of formate. Treatment of this formate
      ligated enzyme with excess cyanide releases 97% of the radiolabel while reduction
      of formate-labeled enzyme with NADH+ruthenium releases 80-85% of the
      radioactivity. These data are most simply interpreted by assuming that formate
      binds to the heme iron of cytochrome a3.

PMID- 8982388
TI  - Translocation of guinea pig p40-phox during activation of NADPH oxidase.
AB  - The superoxide-producing NADPH oxidase consists of membrane-associated cytochrome
      b558 and cytosolic components, p47-phox and p67-phox. Recently, we have found a
      novel cytosolic component, p40-phox, which is tightly associated with p67-phox.
      In this study, we examined the translocation of p40-phox during activation of
      NADPH oxidase in a cell-free system using the membrane and the purified p47
      phox/p67-phox/p40-phox complex. p40-phox was translocated to the membrane by
      arachidonic acid in a dose-dependent manner. The translocation pattern of p40
      phox was similar to those of p47-phox and p67-phox. However, immunoprecipitation
      assay revealed that p40-phox was dissociated from p47-phox and p67-phox during
      activation. The translocation of three cytosolic components was not affected by
      the deletion of GTP-gamma-s from the reaction mixture. Interestingly, a synthetic
      peptide corresponding to carboxyl-terminus of p40-phox inhibited the activation
      of NADPH oxidase and translocation of p40-phox, p47-phox, and p67-phox,
      suggesting that p40-phox might play a role in the activation of NADPH oxidase.
      These observations suggest that p40-phox is dissociated from p67-phox during
      activation, and translocates to the membrane by GTP-gamma-s-independent
      mechanism.

PMID- 8982391
TI  - 21st Congress of the European Society for Medical Oncology. Vienna, Austria,
      November 1-5, 1996. Abstracts.

PMID- 8982390
TI  - The lifetimes and energies of the first excited singlet states of diadinoxanthin
      and diatoxanthin: the role of these molecules in excess energy dissipation in
      algae.
AB  - The lifetimes of the first excited singlet states (2(1)A(g)) of diadinoxanthin
      and diatoxanthin, carotenoids involved in the xanthophyll cycle in some genera of
      algae, have been measured by femtosecond time-resolved optical spectroscopy to be
      22.8 +/- 0.1 ps and 13.3 +/- 0.1 ps, respectively. Using the energy gap law for
      radiationless transitions set forth by Englman and Jortner (Mol. Phys. 18 (1970)
      145-164), these lifetimes correspond to S1 excited state energies of 15210 cm-1
      for diadinoxanthin and 14620 cm-1 for diatoxanthin. The lowest excited singlet
      state energy of Chl a has an energy of 14700 cm-1. The fact that the S1 state
      energy of diadinoxanthin lies above that of Chl a, whereas the S1 state energy of
      diatoxanthin lies below that of Chl a, suggests that the xanthophyll cycle
      involving the enzymatic interconversion of diadinoxanthin and diatoxanthin may
      play a role in regulating energy flow between these molecules and Chl a in many
      species of algae, essentially fulfilling a role identical to that proposed for
      violaxanthin and zeaxanthin in higher plants and green algae (Frank et al. (1994)
      Photosyn. Res. 41, 389-395).

PMID- 8982392
TI  - 35th Annual scientific meeting of the British Society for Clinical Cytology.
      Liverpool, United Kingdom, 15-18 September 1996. Abstracts.

PMID- 8982393
TI  - 5th International Conference on Human Antibodies and Hybridomas. Jerusalem,
      Israel, 14-16 October 1996. Abstracts.

PMID- 8982394
TI  - [JFR'96 book of abstracts].

PMID- 8982395
TI  - [The 96th annual meeting of the Japan Surgical Society. Chiba, Japan. April 10
      12, 1996. Abstracts].

PMID- 8982396
TI  - [The 48th Congress of the Japan Society of Obstetrics and Gynecology, Yokohama
      City, Japan. April 6-9, 1996. Abstracts].

PMID- 8982397
TI  - [The 69th Annual Meeting of Japan Society for Occupational Health. Asahikawa,
      Japan. June 2-5, 1996. Abstracts].

PMID- 8982398
TI  - 6th International Workshop and Conference on Human Leukocyte Differentiation
      Antigens. Kobe, Japan, November 10-14, 1996. Abstracts.

PMID- 8982399
TI  - JERMOV 96. Joint European Research Meetings in Ophthalmology and Vision.
      Montpellier, France, 9-13 October 1996. Abstracts.

PMID- 8982400
TI  - Abnormal desmoglein expression by squamous cell carcinoma cells.
AB  - Abnormal expression of cell adhesion molecules and related proteins has been
      observed in various carcinoma cells. We compared expression patterns of
      desmosomal cadherins, E-cadherin, and cytoplasmic plaque proteins of four
      different human squamous cell carcinoma cell lines and in vivo squamous cell
      carcinoma cells with those of normal human keratinocytes. Unlike normal human
      keratinocytes, the squamous cell carcinoma cells, both in culture and in vivo,
      exhibited diminished or unusual expression of desmoglein 3 and desmoglein 1,
      which bear pemphigus vulgaris and pemphigus foliaceus antigens, respectively.
      Abnormal expression of E-cadherin and cytoplasmic plaque proteins such as
      desmoplakin and plakoglobin was also observed. Western blotting study
      demonstrated that three squamous cell carcinoma cell lines expressed two
      desmogleins with a predominant 150 kDa molecule, and a minor 130 kDa one.
      Although these molecular sizes were similar to those of cultured normal human
      keratinocytes, the 130 kDa desmoglein, which usually carries pemphigus antigenic
      epitopes, was weakly or negatively reactive with pemphigus vulgaris serum. One
      squamous cell carcinoma cell line showed a doublet of 140 and 145 kDa bands in
      addition to the 130 kDa band. All the carcinoma cell lines constantly expressed
      desmoglein 2 and desmoglein 3 mRNA, whereas cultured normal human keratinocytes
      always expressed desmoglein 1 and desmoglein 3 mRNA, with or without desmoglein 2
      mRNA. These findings indicate that the squamous cell carcinoma cells revealed
      abnormal expression of desmoglein isoforms, which may be related to tumor cell
      kinetics such as cell invasion and metastasis.

PMID- 8982401
TI  - Cytokines in alopecia areata: contrasting cytokine profiles in localized form and
      extensive form (alopecia universalis).
AB  - Recent studies have suggested that cytokines play a critical role in the
      pathophysiology of alopecia areata; however, no information is available
      regarding the difference in cytokine profiles in these patients. Serum levels of
      cytokines, including interferon gamma (IFN-gamma), tumor necrosis factor alpha,
      interleukin 1 alpha (IL-1 alpha), IL-2, IL-4, and IL-6, were measured using
      radioimmunoassay or enzyme-linked immunosorbent assay techniques in patients with
      the localized form and the extensive form (alopecia universalis). The serum
      levels of IL-1 alpha and IL-4 were significantly elevated in patients with the
      localized form. In contrast, the serum levels of IFN-gamma and IL-2 were
      significantly elevated in patients with the extensive form. These results
      indicate that immune responses in the localized form and the extensive form of
      alopecia areata are regulated by Th2 cytokines and Th1 cytokines, respectively.

PMID- 8982402
TI  - Cyclosporin A down-regulates the LTA4 hydrolase level in human keratinocyte
      cultures.
AB  - Leukotriene A4 hydrolase is a key enzyme in the biosynthesis of leukotriene B4, a
      potent pro-inflammatory compound. The purpose of this study was to determine the
      capacity of antiinflammatory and anti-proliferative compounds to regulate the
      levels and activity of leukotriene A4 hydrolase in cultured human keratinocytes.
      The content of leukotriene A4 hydrolase was determined by Western blot analysis,
      and the activity of leukotriene A4 hydrolase was expressed as the leukotriene B4
      formation after incubation of keratinocyte cultures with leukotriene A4.
      Leukotriene B4 was measured by revered-phase high performance liquid
      chromatography. Preincubation for 10 min of the cultured keratinocytes with the
      leukotriene A4 hydrolase inhibitor RP 64699 (0.1-10 microM) caused a significant
      dose-dependent inhibition of leukotriene B4 formation (IC50 = 0.7 microM).
      Cyclosporin A (0.1 micrograms/ml and 1.0 micrograms/ml) had no direct effect on
      leukotriene A4 hydrolase activity, but after incubation for 72 h there was a
      decrease in the mean leukotriene B4 formation per culture dish (35% and 48%,
      respectively). The decreased leukotriene B4 formation was caused mainly by a
      decrease in the mean leukotriene A4 hydrolase content per mg protein (30.1% at
      0.1 micrograms/ml cyclosporin A and 40.0% at 1.0 micrograms/ml cyclosporin A),
      although keratinocyte proliferation was also slightly decreased. Incubations with
      1.25-dihydroxyvitamin D3 (10(-7)-10(-10) M), all-trans retinoic acid (10(-6)-10(
      10) M), eicosartienoic acid (10(-6)-10(-8) M), dexamethasone (10(-5)-10(-7) M),
      interferon-gamma (10 and 100 units/ml) or methotrexate (0.1-10 micrograms/ml) had
      no effect on either the leukotriene B4 formation or the amount of leukotriene A4
      hydrolase in keratinocyte cultures. These results show that cyclosporin A, in
      contrast to other anti-inflammatory and anti-proliferative compounds, inhibits
      the level of leukotriene A4 hydrolase in keratinocyte cultures. Since similar
      cyclosporin A concentrations are obtained during treatment of psoriasis with
      cyclosporin A, the effect on leukotriene A4 hydrolase may play a role in the anti
      inflammatory action of cyclosporin A.

PMID- 8982403
TI  - Photoprotection in vitiligo and normal skin. A quantitative assessment of the
      role of stratum corneum, viable epidermis and pigmentation.
AB  - Pigmentation, stratum corneum and viable epidermis are considered to be the main
      factors protecting against ultraviolet radiation. We quantitatively investigated
      the degree of photoprotection provided by these structures in vitiligo and
      adjacent normally pigmented skin. In 14 patients 61 MED tests were performed in
      vitiligo and adjacent normally pigmented skin using a solar simulator. The
      thickness of stratum corneum and viable epidermis was determined from frozen skin
      sections, and pigmentation was calculated by measuring skin reflectance at 555 nm
      and 660 nm. To analyse photoprotection, the UV dose necessary to evoke erythema
      was regressed against the thickness of stratum corneum and viable epidermis,
      pigmentation and the erythema grade in the MED test. By analysing regression
      coefficients we found that stratum corneum was the main photoprotective factor
      not only in vitiligo but also in normally pigmented skin. The effect of
      pigmentation in normal skin was slightly less prominent. Stratum corneum was
      thicker in vitiligo than in normally pigmented skin. However, the photoprotection
      due to stratum corneum was similar in both groups because significantly less
      photoprotection was achieved per thickness unit of stratum corneum in vitiligo
      than in normal skin. Neither in vitiligo nor in normally pigmented skin did the
      photoprotection depend on viable epidermis. Our data quantitatively document the
      importance of stratum corneum and pigmentation. Hyperkeratosis in vitiligo offers
      just as efficient photoprotection as does the normal stratum corneum in pigmented
      skin.

PMID- 8982404
TI  - Clinical histochemical and immunohistochemical investigation of the capillary
      basal membrane in chronic venous insufficiency.
AB  - Present investigations regarding the pathogenesis of chronic venous insufficiency
      (CVI) are focusing on microvascular changes. The aim of our investigation was to
      examine the correlation between the thickness of pericapillary type IV collagen
      depositions, basal membrane alterations and transcutaneous oxygen tension (TcPO2)
      in CVI-patients. Histochemical and immunohistochemical investigation of the
      capillary basal membrane was performed on 15 biopsies from normal controls, as
      well as 30 patients with CVI stage I and III (classification by Widmer &
      Stahelin). In all subjects TcPO2 was measured just prior to biopsy procedures in
      exactly the same area where the specimen was subsequently excised. The
      microscopically measured thickness of the collagen IV layer and the basal
      membrane was increased significantly in patients with CVI. Specimens from normal
      controls showed a collagen IV layer thinner than 0.1 micron. Patients with CVI
      stage III revealed strong collagen IV depositions between 0.2 and 0.3 microns.
      Comparison between TcPO2 and histological findings in the measured ares showed
      oxygen pressure varying from 62 mmHg (SEM 4.94 mmHg) in normal controls, down to
      13 mmHg (SEM 3.39 mmHg) in patients with thick collagen IV layers. Besides an
      increased collagen IV layer, microvascular thrombosis and a thickened basal
      membrane have to be considered for impaired capillary perfusion.

PMID- 8982407
TI  - The in vitro effect of fluconazole on the filamentous form of Pityrosporum ovale.
AB  - The antimycotic activity of fluconazole against the filamentous form of
      Pityrosporum ovale was studied in vitro. P. ovale was grown on human stratum
      corneum in vitro with and without the addition of different concentrations of
      fluconazole. In control cultures hyphae were produced in 25% of the cells
      compared to only 4% after exposure to fluconazole 1 microgram/ml. In control
      cultures 16% of the fungal cells showed signs of necrosis, due to the normal
      turnover rate of the cells, compared to 65% of the fungal cells exposed to 1
      microgram/ml of fluconazole. In the transmission electron microscope the typical
      thick-walled fungal cells with their characteristic budding were observed in
      control cultures. However, after exposure to 1 microgram/ml of fluconazole that
      P. ovale cells showed extensive signs of necrosis, with loss of internal
      organelles and disinterruption of the cell wall. The results obtained in this in
      vitro model mimic the in vivo situation in pityriasis versicolor. There is a
      parallel between the good results obtained in this system and the good clinical
      effect of fluconazole in Pityrosporum-related diseases.

PMID- 8982405
TI  - Antiproliferative effect of pentoxifylline on psoriatic and normal epidermis. In
      vitro and in vivo studies.
AB  - Psoriasis is characterized by abnormal cell proliferation, inflammation and
      increased biosynthesis of various cytokines. The inhibitory effect of
      pentoxifylline on some cell functions has been reported widely. This property of
      pentoxifylline prompted an investigation of its possible role in controlling
      psoriasis. In the in vitro study normal human keratinocytes proliferation was
      determined and formation of cornified envelopes was assayed following treatment
      with pentoxifylline. The in vivo experiment consisted of nude mice grafted with
      psoriatic or normal skin treated with tetradecanyl phorbol 13 acetate. At the end
      of the treatment period, the grafts were excised and assessed for acanthosis and
      labelling index. The in vitro study showed that continuous exposure of normal
      human keratinocyte cultures to pentoxifylline resulted in a significant dose
      dependent inhibition of proliferation, and in induction of cornified envelope
      formation. The in vivo experiments showed a significant reduction of epidermal
      thickness and of labeling index in psoriatic and tetradecanyl phorbol 13 acetate
      treated normal skin, as compared to the initial values.

PMID- 8982406
TI  - Plasma endothelin in psoriasis: possible relations to therapy and toxicity.
AB  - Plasma endothelin levels were studied in 71 patients suffering from severe
      psoriasis. The psoriatics were treated either with topical therapy alone (n = 18)
      or with cyclosporin A (n = 26), methotrexate (n = 21), or with hydroxyurea,
      acitretin or ranitidin (n = 6) with or without topical therapy. The psoriatics
      had a significantly higher average plasma endothelin than 40 healthy controls.
      The patients treated with cyclosporin A had the highest values and these were in
      contrast to patients on methotrexate and other systemic therapy higher than
      patients treated with topical therapy alone. There was not significant difference
      between endothelin levels in patients treated with methotrexate compared to those
      in patients only receiving topical treatment. Whether the increased endothelin
      levels in plasma are derived from keratinocytes or enlarged vessels need to be
      investigated. An increased plasma endothelin level could be related to therapy
      and for patients on cyclosporin A be of importance for toxicity.

PMID- 8982408
TI  - Change of skin roughness due to lowering air humidity in climate chamber.
AB  - Rough skin ("dry skin") is characteristic of atopy and thought to be a pre-stage
      of atopic eczema. Atopic eczema frequently deteriorates in winter, which may be
      related to low air humidity during the heating period. We have assessed skin
      roughness before and after decreasing air humidity to 30% in a climatic chamber.
      Replicas of clinically non-inflamed and not scaling skin from 10 patients with
      atopic eczema and 10 controls were taken before and after lowering air humidity
      for 3 h and were analyzed for the roughness parameters Ra, RZ(DIN) and RZ(ISO).
      After exposure to low air humidity there was a significant increase of RZ(DIN)
      from 61.5 microns to 66.9 microns (p < 0.05) and of RZ(ISO) from 63.8 microns to
      66.4 microns (p < 0.05) in patients with atopic eczema, whereas no significant
      change occurred in controls. Development of skin roughness over 3 h under natural
      indoor environmental conditions did not indicate spontaneous variations. These
      quantitative data show that a short period of exposure to low air humidity
      increases skin roughness and may particularly influence the condition of patients
      with atopic eczema.

PMID- 8982410
TI  - Erythropoietic protoporphyria and terminal hepatic failure.
AB  - We report on a 44-year-old patient with erythropoietic protoporphyria who could
      effectively control his photosensitivity for 22 years with oral carotinoids. The
      clinical course of his disorder was complicated by liver involvement, initially
      expressed as marginally raised serum transaminase levels for several years.
      Terminal hepatic failure with fatal outcome developed 22 years after
      manifestation of his liver function abnormalities. Hepatic involvement represents
      an inconstant and unpredictable feature of erythropoietic protoporphyria,
      determining the prognosis of an otherwise clinically benign disorder.

PMID- 8982409
TI  - Irritancy testing in occupational dermatology: comparison between two quick tests
      and the acute irritation induced by sodium lauryl sulphate.
AB  - To reduce the incidence of irritant contact dermatitis, the development of
      screening methods to identify subjects with increased susceptibility to irritants
      is essential. In a pilot study on the comparison between two quick, non-invasive
      irritancy tests (dimethyl sulfoxide (DMSO) and sodium hydroxide (NaOH) with the
      time-consuming patch testing with sodium lauryl sulphate (SLS), no correlation
      between the "quick tests" and SLS patch testing was observed. In the present
      paper the results of irritancy testing in 181 metal worker trainees are
      presented. Experimental irritant contact dermatitis reactions were induced on the
      medial third of the volar forearm using SLS 0.5%, applied for 23 h and as "quick
      tests" DMSO 90% and 95% and a solution of 0.2% mol/l NaOH applied for 5 min.
      Assessment of skin irritability was made by visual scoring and measurement of
      transepidermal water loss. Except for a statistically significant relationship
      between the irritations by DMSO 90% and 95%, correlations between the different
      techniques were weak or non-existent. This is most probably due to different
      pathophysiological pathways for the irritant reactions. We therefore propose to
      use a spectrum of different tests in occupational dermatology for predicting the
      individual's risk of irritant contact dermatitis.

PMID- 8982411
TI  - Atopic dermatitis may be linked to whether a child is first- or second-born
      and/or the age of the mother.
AB  - Five hundred and thirty families with at least 1 child who had been referred to a
      dermatologist with atopic dermatitis were interviewed in an effort to determine
      whether factors such as the age of the mother when a child is born and/or birth
      rank can contribute to the development of atopic dermatitis. The families
      interviewed had a total of 1,084 children, or an average of 2 children per
      family. Sixty per cent of the children with atopic dermatitis were under 5 years
      of age. Ninety-one per cent of them had developed the disease before the age of
      3; those most severely affected had developed the disease during the first year
      of life. In families with 2 children, but only 1 child with atopic dermatitis,
      the odds ratio for the second child to develop atopic dermatitis was 1.379 (0.025
      < p < 0.05). The average maternal age was 24.8 to 25.2 years when giving birth to
      the first child and 28 years when giving birth to the second child, irrespective
      of the status of the child. Thus, atopic dermatitis can be related to birth rank
      or to the age of the mother.

PMID- 8982412
TI  - Q-switched ruby laser application is safe and effective for the management of
      actinic lentigo (topical glycolic acid is not).
AB  - A study was designed to evaluate the effectiveness of single q-switched ruby
      laser exposure to erase actinic lentigo. A peeling fluid containing glycolic acid
      designed to treat lentigines was evaluated comparatively. Ten female patients
      presenting with actinic lentigines on the forearms and dorsal aspects of their
      hands were treated with the q-switched ruby laser on the right side. Single ruby
      laser irradiation of actinic lentigines on the dorsal aspects of forearms and
      hands caused transient crusting due to exfoliation of the epidermal surface,
      which generally lasted for 2 weeks. Four weeks after treatment total fading of
      the lesions was evident. Topical application of peeling fluid applied on the left
      forearms caused burning sensations, local irritation and superficial scaling but
      could not clear the lentigines. A single course of q-switched ruby laser exposure
      is safe and efficient for the management of actinic lentigines, as it completely
      clears these obvious signs of aging. Topical treatment of lentigines using a
      commercial peeling solution leads to moderate or severe irritation and is
      ineffective.

PMID- 8982413
TI  - Early onset (< 40 years age) psoriasis is comorbid with greater psychopathology
      than late onset psoriasis: a study of 137 patients.
AB  - Early onset (< age 40 years) psoriasis has been reported to be more readily
      triggered by environmental factors such as stress, in contrast to late onset (>
      or = age 40 years) psoriasis. We examined whether certain psychopathologic
      factors differentiated the psoriasis patient with early onset versus late onset
      disease. One hundred and thirty-seven psoriasis inpatients completed a battery of
      psychosocial questionnaires. Logistics regression analysis, using the psychologic
      measures, age and TBSA affected as independent variables, revealed that higher
      Anger-in (Anger Expression Scale) scores significantly (p < 0.05) increased the
      odds or probability of having early versus late onset psoriasis. Psoriasis with
      onset prior to age 40 is comorbid with greater difficulties with assertion and
      expression of anger, a personality trait that may adversely affect the patient's
      capacity to cope with stress.

PMID- 8982414
TI  - Association of psychic stress with clinical severity and symptoms of psoriatic
      patients.
AB  - The association of stress with psoriatic skin and joint symptoms was studied in
      38 patients with psoriasis by dividing the patients into low-stress and high
      stress groups based on their answers to four questionnaires (General health
      questionnaire, Somatization questionnaire, Depression questionnaire, and Life
      change questionnaire), measuring minor psychiatric disorder, psychosomatic
      reactivity, depression and life changes, respectively. Compared to the low-stress
      group (n = 21), the patients in the high-stress group (n = 17) had more severe
      skin and joint symptoms and a higher score, which in established psoriatic
      General severity score that was calculated by judging Psoriasis Area and Severity
      Index, activity of psoriasis and the presence of joint symptoms. All the four
      questionnaires showed higher morbidity frequency and higher score points.
      Actively spreading psoriasis was significantly associated with stressful life
      events for men but not for women. However, in the low-stress group, men had
      experienced significantly fewer stressful events than women. Psoriasis Area and
      Severity Index showed strong correlation with the Somatization score, but no
      differences between men and women. The General severity score correlated with the
      Somatization score, and the higher the General severity score (score > or = 6)
      the higher were all the four questionnaire scores. Also, patients having joint
      symptoms had higher scores in all of the four psychic questionnaires than
      patients without joint symptoms. By the chi-test, female patients with joint
      symptoms showed a significant correlation with the high General health
      questionnaire. The presence of joint symptoms showed a tendency for correlation
      in women with high depression level and in men with high somatization level. This
      study suggests that psychic stress is associated with exacerbation of psoriasis,
      and more attention to mental well-being should be paid at least in the case of
      those psoriatic patients seeking actively for medical care.

PMID- 8982415
TI  - Successful treatment of dyshidrotic hand eczema using tap water iontophoresis
      with pulsed direct current.
AB  - The efficacy of tap water iontophoresis in treating palmoplantar hyperhidrosis
      has been sufficiently documented and has led to its extensive use in clinical
      practice. In order to test the efficacy of this treatment modality in cases of
      dyshidrotic hand eczema, 20 patients were treated with tap water iontophoresis in
      addition to two-sided steroid-free topical therapy in a randomized half-side
      study. A special score for dyshidrotic eczema including objective and subjective
      criteria was developed to document the success of the therapy. Only those sides
      treated with tap water iontophoresis showed significant improvement. This
      significant effect of iontophoresis indicates the efficacy of this treatment in
      cases of dyshidrotic hand eczema.

PMID- 8982416
TI  - PUVA in early mycosis fungoides may give long-term remission and delay
      extracutaneous spread.
AB  - We report a follow-up for 3-18 years of 24 patients with the non-infiltrated
      patch and infiltrated plaque stage of mycosis fungoides, treated with psoralen
      photochemotherapy (PUVA) and on resistant infiltration or development of tumours
      also with fractionated radiation therapy. All patients with patch and limited
      plaques showed complete remission after initial PUVA therapy. Half of the
      patients with patch stage mycosis fungoides and also half of the patients with
      plaque stage mycosis fungoides were in complete remission when the study ended.
      Most of them had remission periods for years after early PUVA treatment. Patients
      with more advanced mycosis fungoides needed repeated periods of PUVA therapy. Two
      patients with extensive infiltrated plaques did not reach complete remission at
      all during the study but progressed and finally died of their T-cell lymphoma.
      Another 4 patients with extensive plaque stage mycosis fungoides died after
      initial complete remission for a maximum of 3 years. In this investigation the
      clinical evaluation was made by one dermatologist and the histopathological
      evaluation by one pathologist. This is of importance since in the early stages of
      mycosis fungoides the diagnosis is challenging and may require a combination of
      clinical, histopathological and molecular evaluations. The identification of
      early disease is crucial for the rapid implementation of adequate treatment. The
      study shows that early PUVA therapy may delay extracutaneous spread and possibly
      also in some cases be curative.

PMID- 8982417
TI  - n-Docosanol 10% cream in the treatment of recurrent herpes labialis: a
      randomised, double-blind, placebo-controlled study.
AB  - n-Docosanol has been shown to have antiviral activity. To demonstrate the
      efficacy of n-docosanol 10% cream in the treatment of recurrent herpes labialis,
      a randomised, double-blind, parallel group, placebo-controlled study was
      undertaken in 63 patients. In a crossover extension, 22 of the patients used the
      alternative treatment for a further episode. A total of 98 episodes were
      evaluated. Application of n-docosanol 10% cream early in the prodromal or
      erythema stage of a recurrent episode of herpes labialis shortened mean healing
      time by approximately 3 days, as compared to late treatment with n-docosanol 10%
      cream and early or late treatment with the placebo. The crossover study revealed
      that late treatment with n-docosanol 10% cream significantly reduced mean healing
      time compared to placebo. Treatments were well tolerated.

PMID- 8982418
TI  - A case-control study of hidradenitis suppurativa in an STD population.
AB  - The prevalence of hidradenitis suppurativa has been found to be higher among
      patients attending an STD clinic than in an unselected general population sample.
      The aetiology of hidradenitis in unknown, but an association with chlamydial
      infections has been suggested for perineal lesions. Our aim was to describe the
      history of STD, STD risk factors and possible current STD in patients with
      hidradenitis. A case-control study comparing patients with hidradenitis (20) and
      controls (60) was therefore made in patients attending an STD clinic. Genital HPV
      infection was found to be more common in patients with hidradenitis (p = 0.036),
      but no differences were seen in the history of STD, STD risk behaviour or other
      current STD between the two groups studied. HPV infection appears to be the only
      STD which is more common in hidradenitis patients, but the biological
      significance of this finding is not clear. It is speculated that common
      predisposing factors may be responsible. We were unable to support the previously
      postulated association between Chlamydia trachomatis infection and hidradenitis.

PMID- 8982419
TI  - Nail surgery: an assessment of indications and outcome.
AB  - To examine the merits of nail surgery, we studied the surgical investigation,
      treatment and the outcome of 78 consecutive patients with nail pathology in the
      context of their complaint. A diagnosis was reached in 74/78 patients. Thirty-six
      out of seventy-eight (46%) of patients had tumours, 17/78 (22%) had a dermatosis,
      21/78 (27%) had infection or trauma and 4/78 (5%) remained undiagnosed. The
      presenting complaint was treated with substantial or complete resolution in 66/78
      (87%) patients. Ninety-seven per cent (35/36) of those with tumours were cured,
      including all 5/36 with malignant and dysplastic tumours. Post-operative
      splitting of the nail was seen in only one patient due to secondary infection of
      a longitudinal nail unit biopsy. Information from this study demonstrates the
      diagnostic and therapeutic value of nail surgery within dermatology.

PMID- 8982420
TI  - Burning mouth syndrome: the role of contact hypersensitivity.
AB  - The burning mouth syndrome is characterized by an unpleasant sensation of burning
      in the oral cavity, without clinical signs. Causal factors may be psychogenic,
      systemic or local. The aim of the study was to determine the significance of
      contact allergy in the pathogenesis of burning mouth syndrome. Fifteen patients
      with burning mouth syndrome were studied through anamnesis and laboratory
      analysis. Epicutaneous patch tests were performed with the Italian standard
      series (GIRDCA - Gruppo Italiano di Ricerca Dermatiti da Contatto ed Ambientali),
      preservative and dental series. The same tests were carried out in 12 healthy age
      and sex-matched subjects. The number of patients affected by burning mouth
      syndrome with a positive reaction to patchtesting was 6 out of 15, while the
      number of allergic patients in the control group was 3 out of 12. No association
      could be found between positive reaction at patchtesting and exposure to
      allergens. Contact allergy in burning mouth syndrome seems not to play a primary
      role; nevertheless, it is advisable to perform patch tests in selected patients
      to identify a possible aetiological agent.

PMID- 8982421
TI  - PUVASOL therapy in palmoplantar psoriasis.

PMID- 8982422
TI  - Increased urinary excretion of N-acetyl-beta-D-glucosaminidase in patients
      affected with psoriasis.

PMID- 8982423
TI  - Langerhans' cells in cervical condyloma and intraepithelial neoplasia in smoking
      and non-smoking adolescents.

PMID- 8982424
TI  - Serum levels of soluble CD14 in scleroderma.

PMID- 8982425
TI  - Tungiasis presenting with sterile pustular lesions on the hand.

PMID- 8982426
TI  - Cutaneous manifestations of Takayasu arteritis.

PMID- 8982429
TI  - Coexistence of subcutaneous sarcoidosis of the sole and scar sarcoidosis.

PMID- 8982428
TI  - Pseudoallergen-free diet in the treatment of chronic urticaria.

PMID- 8982427
TI  - Bullous pemphigoid and diabetes mellitus.

PMID- 8982431
TI  - Gianotti-Crosti syndrome in an adult patient following a recently acquired
      Epstein-Barr virus infection.

PMID- 8982430
TI  - Effectiveness of 4% disodium cromoglycate in the treatment of disseminated
      pyoderma gangrenosum.

PMID- 8982432
TI  - Cutaneous microdialysis. Methodology and validation.
AB  - This thesis describes the methodology and validation of cutaneous microdialysis
      for the study of skin penetration of various topically applied substances in
      experimental dermatological research. Microdialysis is a sampling technique which
      makes it possible to measure substances in the extracellular water space in human
      and animal skin in vivo. A microdialysis probe, i.e. a tubular semipermeable
      membrane connected to afferent and efferent tubings, is placed in the dermis and
      perfused. Substances from extracellular space may diffuse through the pores of
      the membrane and be collected in the dialysate for further analysis. Glucose,
      sodium fusidate, betamethasone 17,21-dipropionate and calcipotriol were chosen as
      model substances and were investigated by in vitro microdialysis. The perfusion
      rate, the length of the membrane, stirring rate and temperature influenced
      recovery of the substances. Lipophilic compounds tend to have low recoveries and
      differ in recovery and loss. Insertion of the microdialysis probe causes a trauma
      in the skin. Rat and human skin were studied in vivo. Increase in skin blood
      flow, erythema and skin thickness were demonstrated by laser Doppler perfusion
      imaging, Dermaspectrometer colorimetry, Minolta Chromameter colorimetry and
      ultrasound imaging of cross-sectional skin structure. In addition histamine was
      released in rat skin due to the needle insertion. An equilibration period of
      minimum 90 min in human skin and 30 min in rat skin after the insertion is
      necessary to allow the effects of trauma to diminish. To obtain measurable
      concentrations in the dialysate in rats treated topically with the lipophilic
      drug betamethasone 17-valerate, unrealistic high doses and penetration
      enhancement were required. The highly protein-bound drug fusidic acid was not
      measurable in the dialysate after topical application, probably due to very low
      concentrations of free diffusible drug. Measurable concentrations were only
      observed after high doses of oral administrations of fusidic acid. Calcipotriol
      could not be detected in the dialysate. The microdialysis technique is probably
      primarily useful for the study of hydrophilic substances and substances with low
      protein binding and low molecular weight. However, application of cutaneous
      microdialysis for the study of lipophilic substances need further
      methodologically development.

PMID- 8982433
TI  - Regulatory effect of danggui-shaoyao-san on central cholinergic nervous system
      dysfunction in mice.
AB  - Since administration of a powdered extract (TSS) of Danggui-Shaoyao-San (Toki
      shakuyaku-san in Japanese) alone to naive mice had no influence on ACh levels in
      the brain, the present study examined the effect of TSS on the central
      cholinergic nervous system using mice treated with scopolamine (0.5 mg/kg) or
      mecamylamine (0.05 mg/kg), which affects the cholinergic nervous system. TSS was
      suspended in a 5% carboxymethylcellulose solution and mice were orally given
      single or repeated (twice a day, for 14 days) administration of TSS at 50 or 500
      mg/kg. Results on spontaneous locomotor activity showed that (1) single
      administration of TSS at 50 or 500 mg/kg to naive mice significantly inhibited
      vertical and horizontal locomotor activities, while repeated administration of
      TSS at 50 mg/kg significantly stimulated both activities; (2) in mice treated
      with scopolamine, repeated administration of TSS at 500 mg/kg significantly
      inhibited the scopolamine-induced increase in locomotor activities, whereas in
      mice treated with mecamylamine, single or repeated administration of TSS at 50
      and 500 mg/kg did not show any influence on the mecamylamine-induced decrease in
      locomotor activities. Regarding the step-down passive avoidance responses; single
      administration, but not repeated administration, of TSS at 50 and 500 mg/kg
      significantly inhibited scopolamine-induced shortening of step-down latency. In
      mice treated with mecamylamine, TSS did not exert any influence on the step-down
      latency. As for ACh contents, single or repeated administration of TSS at 50 or
      500 mg/kg to naive mice had no influence on the levels of ACh in the cerebral
      cortex, corpus striatum or hippocampus. However, the levels of brain ACh in mice
      treated with scopolamine showed a decrease and a single administration of TSS at
      500 mg/kg significantly inhibited this scopolamine-induced decrease in ACh
      levels. These results indicate that TSS ameliorates dysfunction of the central
      cholinergic nervous system and scopolamine-induced decrease in ACh levels in
      mouse brain, but has no influence on ACh levels in naive mice. Thus, it suggests
      that TSS may be a useful therapeutic agent in Alzheimer's disease and senile
      dementia.

PMID- 8982434
TI  - Protective and therapeutic effects of huanglian-jie-du-tang on hepatotoxin
      induced liver injuries.
AB  - The hepatoprotective effect of Huanglian-Jie-Du-Tang (HLJDT), a Chinese medicinal
      prescription, was investigated in three kinds of experimental models. The animals
      were treated with HLJDT (300 mg/kg, p.o.) thrice at 2, 4 and 10 hours after
      administration with carbon tetrachloride (32 microliters/kg, i.p.), acetaminophen
      (600 mg/kg, i.p.) and beta-D-galactosamine (188 mg/kg, i.p.). Significant
      hepatoprotective effects on carbon tetrachloride and acetaminophen induced liver
      injuries were noted, but no significant effect on beta-D-galactosamine induced
      liver injury was observed. These hepatoprotective effects were evidenced by
      comparing the serum glutamate oxaloacetate transaminase (SGOT) and serum
      glutamate pyruvate transaminase (SGPT) levels in HLJDT treated and untreated
      groups. Serum enzyme activities in the carbon tetrachloride and acetaminophen
      experiments were significantly lower in the treated groups while the herbal
      prescription has no effect on the beta-D-galactosamine experiment. These results
      demonstrated that Huanglian-Jie-Du-Tang has a hepatoprotective effect against
      experimental liver injuries induced by specific hepatotoxins, and therefore may
      be useful in treating some, but not all, liver injuries.

PMID- 8982435
TI  - The hepatoprotective effects of Taiwan folk medicine ham-hong-chho in rats.
AB  - Bidens pilosa L. var minor (Blume) Sherff, B. pilosa L. and B. chilensis DC
      (compositae), commonly known as "Ham-hong-chho" in Taiwan, have been
      traditionally used for medicinal purposes. To clarify and compare the
      hepatoprotective effects of these three plants, we evaluated their potential
      effectiveness on CCl4- and acetaminophen-induced acute hepatic lesions in rats.
      The results indicated that the increase in SGOT and SGPT activities caused by
      CCl4 (3.0 ml/kg, s.c.) and acetaminophen administration (600 mg/kg, i.p.) could
      be significantly reduced by treating with the extracts of all the three kinds of
      "Ham-hong-chho" and the extract of B. chilensis exhibited the greatest
      hepatoprotective effects. These phenomena were also confirmed by histological
      observation. Liver damage induced by CCl4 and acetaminophen was markedly improved
      in the extract of B. chilensis treated groups, while groups treated with the
      extracts of B. pilosa var minor and B. pilosa demonstrated only moderate
      protective effects. The pharmacological and pathological effects of these three
      crude groups were compared with Bupleurum chinense, which has been reported
      previously as a treatment criteria in the CCl4 model, and with silymarin as a
      standard reference medicine in the acetaminophen model. The results suggest that
      B. pilosa var minor, B. pilosa and B. chilensis can protect liver injuries from
      various hepatotoxins and have potential as broad spectrum antihepatic agents.

PMID- 8982436
TI  - Hachimi-jio-gan extract protects the kidney from hypertensive injury in Dahl salt
      sensitive rat.
AB  - We investigated whether the Chinese herbal remedy, Hachimi-jio-gan extract,
      attenuates the renal injury seen in salt-induced hypertension in Dahl salt
      sensitive (Dahl S) rats. Administration of this extract for 5 weeks dose
      dependently decreased systolic blood pressure in Dahl S rats fed with a high-salt
      (2% NaCl) diet. This blood pressure reduction was associated with a decrease in
      cardiac mass and in thickness of the aortic wall. Urinary excretion of
      prostaglandin E2 was increased and glomerular filtration rate was improved with
      this treatment. Glomerulosclerosis and arterial injury in the kidney were
      morphologically improved. These data suggest that Hachimi-jio-gan extract
      exhibits an antihypertensive effect, which is associated with partial resolution
      of renal injury in salt-induced hypertension.

PMID- 8982438
TI  - Investigation of the anti-inflammatory activity of Acacia nilotica and Hibiscus
      sabdariffa.
AB  - The aqueous extracts of Acacia nilotica and Hibiscus sabdariffa were tested for
      anti-inflammatory, analgesic and antipyretic activities in animal models. Acacia
      nilotica extract had an inhibitory effect on carrageenan induced paw edema and
      yeast-induced pyrexia in rats. It also produced a significant increase in the hot
      plate reaction time in mice. Hibiscus sabdariffa extract had no effect on paw
      edema but had an inhibitory effect on yeast induced pyrexia and a significant
      effect on the hot plate reaction time. Among the phytoconstituents found in both
      plants, flavanoids, polysaccharides and organic acids may be mainly responsible
      for their pharmacological activities.

PMID- 8982437
TI  - Schisandra chinensis-dependent myocardial protective action of sheng-mai-san in
      rats.
AB  - Sheng-Mai-San (SMS), a traditional Chinese formulation used for the treatment of
      coronary heart disease, is comprised of Radix Ginseng, Fructus Schisandrae and
      Radix Ophiopogonis. Pretreatment with a lignan-enriched SMS (17 g/kg/day x 3,
      p.o.) was found effective in protection against isoproterenol-induced myocardial
      injury in rats, and in ischemia-reperfusion injury in isolated perfused hearts
      prepared from pretreated animals. Results obtained from pretreatment studies
      using extracts prepared by mixing various combinations of the three component
      herbs indicate that the major myocardial protective component in SMS is the
      lignan-enriched extract of Fructus Schisandrae.

PMID- 8982439
TI  - Enhancement of nitric oxide production from activated macrophages by
      glycyrrhizin.
AB  - We studied the actions of glycyrrhizin on nitric oxide production from
      macrophages and a macrophage cell line RAW264-7. Although glycyrrhizin did not
      induce nitric oxide from resting macrophages, it enhanced the production of
      nitric oxide from IFN-gamma activated-macrophages or RAW cells. Glycyrrhizin also
      enhanced the production of nitric oxide from macrophages stimulated with the
      supernatant of con A-activated spleen cells. Further, glycyrrhizin enhanced tumor
      cell killing by macrophages activated with IFN-gamma. This tumor cell killing was
      mainly by nitric oxide.

PMID- 8982440
TI  - Effects of Glycyrrhizae and Glycyrrhizic acid on radiation injury in mice.
AB  - The effects of Glycyrrhizae (GL) and Glycyrrhizic acid (GA) on promoting the
      recovery of mice from radiation injury were investigated. Two hundred ICR strain
      male mice, 6-8 weeks old, were randomly divided into four groups. Group A was the
      normal control. Group B, the experimental control, was treated with 4 Gy gamma
      ray irradiation. Groups C and D, the experimental groups, were treated with 500
      mg/kg of GL (oral administration) and 5 mg/kg body weight of GA (i.p.),
      respectively, for ten days after gamma-ray irradiation. Eight mice in each group
      were sacrificed on days 5, 12, 26 and 33 post irradiation to measure the weights
      of spleen, thymus and testes, and the biosynthetic rates of DNA in these organs.
      The results revealed that 4 Gy gamma-ray irradiation evidently inhibited the
      weights of spleen, thymus and testes, and their DNA biosynthetic rates. GL and GA
      enhanced the recovery of these organs in mice from the injury of gamma-ray
      irradiation.

PMID- 8982441
TI  - Metabolism and disposition of kyushin, a drug containing senso (ch'an su).
AB  - The method of enzyme immunoassay (EIA) was developed for measurement of anti
      resibufogenin IgG reactive substance (RRS) in plasma and urine of healthy
      volunteers receiving a Senso containing drug, Kyushin (KY). Unchanged bufalin
      (BF), cinobufagin (CB), and resibufogenin (RB) and their metabolites in plasma
      and urine were also measured by EIA after the separation of these compounds by
      high performance liquid chromatography. In a single dosing study, the
      concentration of BF, CB and RB in plasma reached maximum at 1-2 hr after drug
      administration, and the half-lives (T1/2 of these were 15.8, 8.94 and 11.5 hr,
      respectively. In a multiple dosing study, the concentration of BF, CB and RB
      measured fitted on the estimated curve calculated from data of the single dosing
      study. These results suggest that BF, CB and RB, important components of Senso,
      do not have a cumulative nature.

PMID- 8982442
TI  - Effect of acupuncture at tai-tsih (K-3) on the pulse spectrum.
AB  - The frequency specific acupuncture effect on Tai-Tsih (K-3) was examined by
      investigating pulse variations at the radial artery. The harmonic proportions of
      the 2nd, 3rd, and the 4th harmonics were increased but the 5th, 6th and 9th
      harmonics were decreased significantly. The phase angles of all except the 2nd
      harmonic were increased (wave propagated slower). These results are compared with
      the frequency specific acupuncture effect on Tsu-San-Li (St-36) which we reported
      previously (Wang et al., 1995a). This study solidified the weak coupling
      resonance theory, which successfully explains these frequency specific effects as
      well as the acupuncture mechanism.

PMID- 8982443
TI  - Pulse spectrum analysis of hospital patients with possible liver problems.
AB  - Pulse diagnosis were performed on 85 patients who came to the hospital for liver
      and gall-bladder problems. Correlation between liver tests, which include T-Bil,
      D-Bil, SGOT, SGPT, ZTT, Alp, gamma-GT, Cho, Alb, and ultra sound scanning, and
      pulse diagnosis were analyzed. 77 out of 85 subjects showed abnormal liver tests.
      We used the following 5 criteria for pulse diagnosis as liver abnormality to test
      the correlation: (1) C1 > or = 3+ and C1 + C4 > or = 4+ or C1 + C6 > or = 4 (in
      intensity); (2) C1 < or = 3 (in intensity); (3) C6 > or = 3 and C1 + C6 > or = 4
      (in intensity); (4) C6 < or = -2 (in intensity) and C6 < or = -2 (in the phase)
      and (5) C1 > or = 2 C3 < or = -2 (in intensity) or C3 < or = -2 (in the phase).
      For C1 (liver) every 5% above normal was given one "+," every 5% below normal was
      given one "-." For C3 (spleen), C4 (lung), C6 (gall-bladder), every 10% above
      normal was given one "+,", every 10% below normal was given one "-." For the
      phase, every 10% delay in the traveling speed was given one "-." When considering
      only the "+" and "-" states and neglecting the quantity of "+" and "-," there are
      2(11) (from intensity) x 2(11) (from phase), which equal 2048 x 2048 possible
      states in the pulse analysis. We considered only 5 criteria for liver
      abnormality; the correlation was still very high, p < 0.0002, kappa = 0.64. It
      strongly suggests that meridian theory and pulse diagnosis have physiological and
      pathological importance.

PMID- 8982444
TI  - Antitussive effect of herbal medicine bakumondo-to: a case report.
AB  - A 50 year-old woman with progressive systemic sclerosis accompanied by
      interstitial pneumonia complained of a dry cough. A variety of antitussive agents
      were given for the dry cough over a one year period, but her symptoms continued.
      However, when a herbal medicine Bakumondo-to was administered, her intractable
      dry cough subsided dramatically within 10 days. Bakumondo-to may be a good
      antitussive agent for interstitial pneumonia associated with a dry cough that is
      resistant to other antitussives.

PMID- 8982445
TI  - Effects of guizhi-fuling-wan on male infertility with varicocele.
AB  - Thirty-seven infertile patients with varicocele were treated with Guizhi-Fuling
      Wan (7.5 g/day) for at least 3 months. Before and after the administration, semen
      qualities such as sperm concentration and motility were examined, and the
      varicocele was graded. A varicocele disappearance rate of 80% was obtained with
      40 out of 50 varicocele, and improvement of sperm concentration and motility were
      found in 71.4% and 62.1% of patients, respectively. From these results, Guizhi
      Fuling-Wan is considered to be effective for circulation disorders in varicocele
      as well as semen quality.

PMID- 8982446
TI  - Motoo Kimura.

PMID- 8982447
TI  - Genetic analysis of the mitotic spindle.
AB  - Much of our understanding of the molecular basis of mitotic spindle function has
      been achieved within the past decade. Studies utilizing genetically tractable
      organisms have made important contributions to this field and these studies form
      the basis of this review. We focus upon three areas of spindle research: spindle
      poles, centromeres, and spindle motors. The structure and duplication mechanisms
      of spindle poles are considered as well as their roles in organizing spindle
      microtubules. Centromeres vary considerably in their size and complexity. We
      describe recent progress in our understanding of the relatively simple
      centromeres of the yeast Saccharomyces cerevisiae and the complex centromeres
      that are more typical of eukaryotic cells. Microtubule-based motor proteins that
      generate the characteristic spindle movements have been identified in recent
      years and can be grouped into families defined by conserved primary sequence and
      mitotic function.

PMID- 8982448
TI  - Control of transcription termination in prokaryotes.
AB  - A growing number of genetic systems have been shown to be controlled at the level
      of premature termination of transcription. Genes in this class contain
      transcription termination signals in the region upstream of the coding sequence.
      The activity of these regulatory termination signals is controlled through a
      variety of mechanisms. These include modification of RNA polymerase to a
      terminator-resistant, or terminator-prone form, and alterations in the structure
      of the nascent transcript, to determine whether the stem-loop structure of an
      intrinsic terminator or an alternate antiterminator is formed. Structural
      alterations in the transcript can be controlled by the kinetics of translation of
      the RNA, by binding of specific regulatory proteins, and by mRNA-tRNA
      interactions. This review describes a number of variations on the termination
      control theme that have been uncovered in prokaryotes.

PMID- 8982449
TI  - Heterocyst formation.
AB  - Heterocysts are microaerobic, N2-fixing cells that form in a patterned array
      within O2-producing filamentous cyanobacteria. Structural features of heterocysts
      can be predicted from consideration of their physiology. This review focuses on
      the spacing mechanism that determines which cells will differentiate, and on the
      regulation of the progression of the differentiation process. Applicable genetic
      tools, developed primarily using Anabaena PCC 7120, but employed also with Nostoc
      spp., are reviewed. These tools include localization of transcription using
      fusions to lux, lac, and gfp, and mutagenesis with oriV-containing derivatives of
      transposon Tn5. Mature and developing heterocysts inhibit nearby vegetative cells
      from differentiating; genes patA, devA, hetC, and the hetMNI locus may hold keys
      to understanding intercellular interactions that influence heterocyst formation.
      Regulatory and other genes that are transcriptionally activated at different
      times after nitrogen stepdown have been identified, and should permit analysis of
      mechanisms that underlie the progression of heterocyst differentiation.

PMID- 8982450
TI  - Bacterial diversity based on type II DNA topoisomerase genes.
AB  - Type II DNA topoisomerases are essential and ubiquitous DNA metabolic enzymes
      that alter DNA topology. Eubacteria have two indispensable type II DNA
      topoisomerases, DNA gyrase encoded by gyrB and gyrA and topoisomerase IV encoded
      by parE and parC. These genes belong to a single family whose members span both
      eukaryotes and prokaryotes. The highly conserved motifs in these genes provide a
      rationale for the design of universal primers used in the polymerase chain
      reaction in order to systematically generate a data set suitable for bacterial
      diversity studies at the macro-diversity level, as well as at the micro-diversity
      level displaying individual species and isolates. This family of genes is the
      subject of intensive biochemical and genetic analyses, which provide an
      opportunity for comprehensive understanding of sequence conservation and
      variability and their relationship to function. These genes are ideally suited
      for microbial identification and biodiversity analyses.

PMID- 8982451
TI  - Prions and RNA viruses of Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae is host to the dsRNA viruses L-A (including its killer
      toxin-encoding satellite, M) and L-BC, the 20S and 23S ssRNA replicons, and the
      putative prions, [URE3] and [PSI]. review the genetic and biochemical evidence
      indicating that [URE3] and [PSI] are prion forms of Ure2p and Sup35p,
      respectively. Each has an N-terminal domain involved in propagation or generation
      of the prion state and a C-terminal domain responsible for the protein's normal
      function, nitrogen regulation, or translation termination, respectively. The L-A
      dsRNA virus expression, replication, and RNA packaging are reviewed. L-A uses a 
      1 ribosomal frameshift to produce a Gag-Pol fusion protein. The host SK12, SK13
      and SK18 proteins block translation of nonpoly(A) mRNAs (such as viral mRNA).
      Mutants deficient in 60S ribosomal subunits replicate L-A poorly, but not if
      cells are also ski-. Interaction of 60S subunits with the 3' polyA is suggested.
      SKI1/XRN1 is a 5'--> 3' exoribonuclease that degrades uncapped mRNAs. The viral
      Gag protein decapitates cellular mRNAs apparently to decoy this enzyme from
      working on viral mRNA.

PMID- 8982452
TI  - Structure, function, and replication of Saccharomyces cerevisiae telomeres.
AB  - A combination of classical genetic, biochemical, and molecular biological
      approaches have generated a rather detailed understanding of the structure and
      function of Saccharomyces telomeres. Yeast telomeres are essential to allow the
      cell to distinguish intact from broken chromosomes, to protect the end of the
      chromosome from degradation, and to facilitate the replication of the very end of
      the chromosome. In addition, yeast telomeres are a specialized site for gene
      expression in that the transcription of genes placed near them is reversibly
      repressed. A surprisingly large number of genes have been identified that
      influence either telomere structure or telomere function (or both), although in
      many cases the mechanism of action of these genes is poorly understood. This
      article reviews the recent literature on telomere biology and highlights areas
      for future research.

PMID- 8982453
TI  - Parental imprinting and human disease.
AB  - Parental imprinting is a process that results in allele-specific differences in
      transcription, DNA methylation, and DNA replication timing. Imprinting plays an
      important role in development, and its deregulation can cause certain defined
      disease states. Absence of a paternal contribution to chromosome 15q11-q13, due
      to hemizygous deletion or uniparental disomy, results in the Prader-Willi
      syndrome. The absence of a normal maternal copy of the same region causes
      Angelman syndrome. The Beckwith-Wiedemann syndrome is associated with the failure
      of normal biparental inheritance of chromosome 11p15, and loss of imprinting is
      observed in several cancers including Wilms' tumor. The study of the molecular
      basis of abnormal imprinting in these disorders will facilitate the
      identification and characterization of other imprinted human disease loci.

PMID- 8982454
TI  - The cytoskeleton and disease: genetic disorders of intermediate filaments.
AB  - Specialized cytoskeletons play many fascinating roles, including mechanical
      integrity and wound-healing in epidermal cells, cell polarity in simple
      epithelia, contraction in muscle cells, hearing and balance in the inner ear
      cells, axonal transport in neurons, and neuromuscular junction formation between
      muscle cells and motor neurons. These varied functions are dependent upon
      cytoplasmic networks of actin microfilaments (6 nm), intermediate filaments (10
      nm) and microtubules (23 nm), and their many associated proteins. In this
      chapter, I review what is known about the cytoskeletons of intermediate filaments
      and their associated proteins. I focus largely on epidermal cells, which devote
      most of their protein-synthesizing machinery to producing an extensive
      intermediate filament network composed of keratin. Recent studies have shown that
      many of the devastating human disorders that arise from degeneration of this cell
      type have as their underlying basis either defects in the genes encoding keratins
      or abnormalities in keratin IF networks. I discuss what we know about the
      functions of IFs, and how the link to genetic disease has enhanced this
      understanding.

PMID- 8982455
TI  - Mammals that break the rules: genetics of marsupials and monotremes.
AB  - Marsupials and monotremes, the mammals most distantly related to placental
      mammals, share essentially the same genome but show major variations in
      chromosome organization and function. Rules established for the mammalian genome
      by studies of human and mouse do not always apply to these distantly related
      mammals, and we must make new and more general laws. Some examples are
      contradictions to our assumption of frequent genome reshuffling in vertebrate
      evolution, Ohno's Law of X chromosome conservation, the Lyon Hypothesis of X
      chromosome inactivation, sex chromosome pairing, several explanations of
      Haldane's Rule, and the theory that mammalian Y chromosome contains a male
      specific gene with a direct dominant action on sex determination. Significantly,
      it is not always the marsupials and monotremes (usually considered the weird
      mammals) that are exceptional. In many features, it appears that humans and,
      particularly, mice are the weird mammals that break more general mammalian, or
      even vertebrate rules.

PMID- 8982456
TI  - Population genetic perspectives on the evolution of recombination.
AB  - Optimality arguments and modifier theory are reviewed as paradigms for the study
      of the evolution of recombination. Optimality criteria (such as maximization of
      mean fitness) may agree with results from models developed in terms of the
      evolution of recombination at modifier loci. Modifier models demonstrate,
      however, that equilibrium mean fitness can decrease during the evolution of
      recombination rates and is not always maximized. Therefore, optimality arguments
      do not successfully predict the conditions under which increased or decreased
      recombination will evolve. The results from modifier models indicate that
      decreased recombination rates are usually favored when the population is
      initially near a polymorphic equilibrium with linkage disequilibrium. When the
      population is subject to directional selection or to deleterious mutations,
      increased recombination may be favored under certain conditions, provided that
      there is negative epistasis among alleles.

PMID- 8982457
TI  - Molecular genetics of sporulation in Bacillus subtilis.
AB  - The process of sporulation in the bacterium Bacillus subtilis proceeds through a
      well-defined series of morphological stages that involve the conversion of a
      growing cell into a two-cell-chamber sporangium within which a spore is produced.
      Over 125 genes are involved in this process, the transcription of which is
      temporally and spatially controlled by four DNA-binding proteins and five RNA
      polymerase sigma factors. Through a combination of genetic, biochemical, and cell
      biological approaches, regulatory networks have been elucidated that explicitly
      link the activation of these sigma factors to landmark events in the course of
      morphogenesis and to each other through pathways of intercellular communication.
      Signals targeting proteins to specific subcellular localizations and governing
      the assembly of macromolecular structures have been uncovered but their nature
      remains to be determined.

PMID- 8982458
TI  - Human type 1 diabetes and the insulin gene: principles of mapping polygenes.
AB  - We review the strategy used to identify a susceptibility locus (IDDM2) for type 1
      (insulin dependent) diabetes mellitus. As type 1 diabetes is becoming the
      paradigm for dissecting multifactorial disease genetics, the approach described
      provides important general guidelines for positional cloning of human disease
      polygenes. Main topics include: (a) historical conspectus of the mapping and
      identification of IDDM2--a critical survey of the work leading up to the
      conclusion that IDDM2 most likely corresponds to allelic variation at the insulin
      gene minisatellite (VNTR) locus; (b) the nature of allelic (length and sequence)
      variation at the VNTR locus; (c) gene interactions and disease pathogenesis; (d)
      mechanism of action of the INS VNTR in type 1 diabetes--insulin gene expression,
      parent-of-origin effects (genomic imprinting); and (e) summary and future
      prospects--alleles of the insulin VNTR that are protective for type 1 diabetes
      appear to encode susceptibility to type 2 diabetes.

PMID- 8982459
TI  - Phylogenetic analysis in molecular evolutionary genetics.
AB  - Recent developments of statistical methods in molecular phylogenetics are
      reviewed. It is shown that the mathematical foundations of these methods are not
      well established, but computer simulations and empirical data indicate that
      currently used methods such as neighbor joining, minimum evolution, likelihood,
      and parsimony methods produce reasonably good phylogenetic trees when a
      sufficiently large number of nucleotides or amino acids are used. However, when
      the rate of evolution varies extensively from branch to branch, many methods may
      fail to recover the true topology. Solid statistical tests for examining the
      accuracy of trees obtained by neighbor joining, minimum evolution, and least
      squares method are available, but the methods for likelihood and parsimony trees
      are yet to be refined. Parsimony, likelihood, and distance methods can all be
      used for inferring amino acid sequences of the proteins of ancestral organisms
      that have become extinct.

PMID- 8982460
TI  - Ubiquitin-dependent protein degradation.
AB  - A growing number of cellular regulatory mechanisms are being linked to protein
      modification by the polypeptide ubiquitin. These include key transitions in the
      cell cycle, class I antigen processing, signal transduction pathways, and
      receptor-mediated endocytosis. In most, but not all, of these examples,
      ubiquitination of a protein leads to its degradation by the 26S proteasome.
      Following attachment of ubiquitin to a substrate and binding of the ubiquitinated
      protein to the proteasome, the bound substrate must be unfolded (and eventually
      deubiquitinated) and translocated through a narrow set of channels that leads to
      the proteasome interior, where the polypeptide is cleaved into short peptides.
      Protein ubiquitination and deubiquitination are both mediated by large enzyme
      families, and the proteasome itself comprises a family of related but
      functionally distinct particles. This diversity underlies both the high substrate
      specificity of the ubiquitin system and the variety of regulatory mechanisms that
      it serves.

PMID- 8982461
TI  - The role of DNA methylation in cancer genetic and epigenetics.
AB  - The past few years have seen a wider acceptance of a role for DNA methylation in
      cancer. This can be attributed to three developments. First, the documentation of
      the over-representation of mutations at CpG dinucleotides has convincingly
      implicated DNA methylation in the generation of oncogenic point mutations. The
      second important advance has been the demonstration of epigenetic silencing of
      tumor suppressor genes by DNA methylation. The third development has been the
      utilization of experimental methods to manipulate DNA methylation levels. These
      studies demonstrate that DNA methylation changes in cancer cells are not mere by
      products of malignant transformation, but can play an instrumental role in the
      cancer process. It seems clear that DNA methylation plays a variety of roles in
      different cancer types and probably at different stages of oncogenesis. DNA
      methylation is intricately involved in a wide diversity of cellular processes.
      Likewise, it appears to exert its influence on the cancer process through a
      diverse array of mechanisms. It is our task not only to identify these
      mechanisms, but to determine their relative importance for each stage and type of
      cancer. Our hope then will be to translate that knowledge into clinical
      applications.

PMID- 8982462
TI  - Proteases and their targets in Escherichia coli.
AB  - Proteolysis in Escherichia coli serves to rid the cell of abnormal and misfolded
      proteins and to limit the time and amounts of availability of critical regulatory
      proteins. Most intracellular proteolysis is initiated by energy-dependent
      proteases, including Lon, ClpXP, and HflB; HflB is the only essential E. coli
      protease. The ATPase domains of these proteases mediate substrate recognition.
      Recognition elements in target are not well defined, but are probably not
      specific amino acid sequences. Naturally unstable protein substrates include the
      regulatory sigma factors for heat shock and stationary phase gene expression,
      sigma 32 and RpoS. Other cellular proteins serve as environmental sensors that
      modulate the availability of the unstable proteins to the proteases, resulting in
      rapid changes in sigma factor levels and therefore in gene transcription. Many of
      the specific proteases found in E. coli are well-conserved in both prokaryotes
      and eukaryotes, and serve critical functions in developmental systems.

PMID- 8982463
TI  - Programmed translational frameshifting.
AB  - Errors that alter the reading frame occur extremely rarely during translation,
      yet some genes have evolved sequences that efficiently induce frameshifting.
      These sequences, termed programmed frameshift sites, manipulate the translational
      apparatus to promote non-canonical decoding. Frameshifts are mechanistically
      diverse. Most cause a -1 shift of frames; the first such site was discovered in a
      metazoan retrovirus, but they are now known to be dispersed quite widely among
      evolutionarily diverse species. +1 frameshift sites are much less common, but
      again dispersed widely. The rarest form are the translational hop sites which
      program the ribosome to bypass a region of several dozen nucleotides. Each of
      these types of events are stimulated by distinct mechanisms. All of the events
      share a common phenomenology in which the programmed frameshift site causes the
      ribosome to pause during elongation so that the kinetically unfavorable
      alternative decoding event can occur. During this pause most frameshifts occur
      because one or more ribosome-bound tRNAs slip between cognate or near-cognate
      codons. However, even this generalization is not entirely consistent, since some
      frameshifts occur without slippage. Because of their similarity to rarer
      translational errors, programmed frameshift sites provide a tool with which to
      probe the mechanism of frame maintenance.

PMID- 8982464
TI  - Paralogous Hox genes: function and regulation.
AB  - The Hox homeobox gene family plays a pivotal role in regulating patterning and
      axial morphogenesis in vertebrates. Molecular characterization of the four Hox
      clusters has shown that they are evolutionarily related with respect to sequence,
      organization, and expression, suggesting they arose by duplication and
      divergence. Transgenic analysis has clearly demonstrated the functional roles of
      individual genes in a broad range of embryonic tissues, and in compound mutants
      has addressed the issues of cooperativity and redundancy. There is an emerging
      picture of the cis-regulatory elements underlying Hox expression, and for the 3'
      members of the clusters there is a considerable degree of conservation between
      paralogous genes with respect to their functional roles and regulatory control.

PMID- 8982465
TI  - Genome downsizing during ciliate development: nuclear division of labor through
      chromosome restructuring.
AB  - The ciliated protozoa divide the labor of germline and somatic genetic functions
      between two distinct nuclei. The development of the somatic (macro-) nucleus from
      the germinal (micro-) nucleus occurs during sexual reproduction and involves
      large-scale, genetic reorganization including site-specific chromosome breakage
      and DNA deletion. This intriguing process has been extensively studied in
      Tetrahymena thermophila. Characterization of cis-acting sequences, putative
      protein factors, and possible reaction intermediates has begun to shed light on
      the underlying mechanisms of genome rearrangement. This article summarizes the
      current understanding of this phenomenon and discusses its origin and biological
      function. We postulate that ciliate nuclear restructuring serves to segregate the
      two essential functions of chromosomes: the transmission and expression of
      genetic information.

PMID- 8982466
TI  - Genetics and molecular analysis of circadian rhythms.
AB  - The first part of this review summarizes the two best understood aspects of the
      two best understood circadian systems, the feedback oscillators of Neurospora and
      Drosophila, concentrating on what we know about the frequency (frq), period (per)
      and timeless (tim) genes. In the second part, the general circadian genetic and
      molecular literature is surveyed, with an eye to describing what is known from a
      variety of systems about input to the oscillator (entrainment), and how the
      oscillator might work and be temperature compensated, in emerging systems
      including Synechococcus, Gonyaulax, Arabidopsis, hamsters, and mice. Finally, the
      conversation of the molecular components of clocks is analyzed: both frq and per
      are widely conserved in their respective phylogenetic classes. Pharmacological
      data suggests that most other organisms use a day-phased oscillator of the type
      seen in Neurospora rather than a night-phased oscillator such as in Drosophila.

PMID- 8982467
TI  - Tumor suppressor gene mutations in mice.
AB  - Over the past several years, a number of human tumor suppressor genes have been
      cloned and characterized. Germline mutations in tumor suppressor genes strongly
      predispose to cancer, and they are also mutated somatically in sporadic forms of
      the disease. In order to create animal models for the familial cancer syndromes
      caused by inherited mutations in these genes as well as to determine their role
      in embryogenesis, the homologues of several members of this class have been
      mutated in the mouse. The initial characterization of the heterozygous and
      homozygous phenotypes caused by these mutations has led to important insights
      into the mechanisms by which tumor suppressor genes participate in normal
      development and how their loss contributes to tumorigenesis.

PMID- 8982468
TI  - Vive la difference: males vs females in flies vs worms.
AB  - For 600 million years, the two best-understood metazoan species, the nematode
      Caenorhabditis elegans and fruit fly Drosophila melanogaster, have developed
      independent strategies for solving a biological problem faced by essentially all
      metazoans: how to generate two sexes in the proper proportions. The genetic
      program for sexual dimorphism has been a major focus of research in these two
      organisms almost from the moment they were chosen for study, and it may now be
      the best-understood general aspect of their development. In this review, we
      compare and contrast the strategies used for sex determination (including dosage
      compensation) between "the fly" and "the worm" and the way this understanding has
      come about. Although no overlap has been found among the molecules used by flies
      and worms to achieve sex determination, striking similarities have been found in
      the genetic strategies used by these two species to differentiate their sexes.

PMID- 8982469
TI  - Factors contributing to the temperature rise during polymerization of resin
      modified glass-ionomer cements.
AB  - Part of the setting reaction of a resin-modified glass-ionomer cement (RMGIC) is
      a photoinitiated polymerization. As a result of the polymerization exotherm, the
      temperature of the cement may rise during setting. This study investigated the
      temperature rise for two liner/base- and two restorative-type RMGICs. The effects
      of factors such as specimen thickness, exposure time and environment temperature
      were investigated. The thermal diffusivity of the cements was also evaluated.
      Temperatures were measured using a thermocouple embedded in the centre of 6-mm
      diameter specimen discs of 1, 2, or 3 mm thickness. The exposure times used to
      cure the specimens varied from 15 to 60 s. The test were carried out at either 25
      or 37 degrees C. The temperature rises attributable to the polymerization
      reaction ranged from 11 to 26 degrees C for the liner/base cements and from 8 to
      17 degrees C for the restorative cements. Increasing the specimen thickness
      reduced the temperature rise only when inadequate exposure times were used.
      Raising the environmental temperature resulted in a smaller temperature rise. The
      thermal diffusivities were determined from cylindrical specimens. These ranged
      from 1.9 x 10(-3) to 2.5 x 10(-3) cm2 s-1, the lining cements showing lower
      values than the restorative materials.

PMID- 8982470
TI  - Light initiation of dental resins: dynamics of the polymerization.
AB  - Literature has shown that slowing down the curing rate of light-initiated resin
      composites by lowering the light intensity of the light source improved the
      integrity of the adhesive composite-cavity interface as a result of a more
      gradual contraction stress development. This study investigated how the curing
      rate could be controlled by varying the concentrations of the photoinitiator
      components in BisGMA-TEGDMA resin. Conversions and curing rates were evaluated by
      linear contraction experiments and Fourier transform infrared spectroscopy.
      Curing rates could be moderated significantly be reducing the concentrations of
      both photoinitiator and reducing agent without affecting the conversion, provided
      that the light exposure with a standard dental light curing unit lasts for 60 s.

PMID- 8982471
TI  - Histological evaluation of freeze-dried dura mater (FDDMA) used in guided bone
      regeneration (GBR): a time course study in man.
AB  - In 26 patients freeze-dried dura mater (FDDMA) membranes were used in
      fenestrations and dehiscences around dental implants, in implants inserted into
      postextraction sockets, in vertical ridge augmentation and in sinus lifting
      procedures. A re-entry procedure was carried out after 6, 9 and 12 months. In all
      patients a small portion of the membrane was removed and examined. No
      inflammatory infiltrate was present in the tissues around the membranes. No cells
      were present inside the membranes and only in the most peripheral portions was it
      possible to observe a few cells positive to acid phosphatase. The FDDMA membranes
      appeared to resorb slowly, did not seem to elicit an inflammatory reaction, and
      at 12 months they still appeared to play a role in cell occlusion.

PMID- 8982472
TI  - Morphology of rod stock and compression-moulded sheets of ultra-high-molecular
      weight polyethylene used in orthopaedic implants.
AB  - Compression-moulded sheets and extruded rods of ultra-high-molecular-weight
      polyethylene (UHMWPE) are currently used in the production of joint replacement
      prostheses. Crystallographic texture present in rods and sheets of UHMWPE was
      measured using a combination of small-angle X-ray scattering and wide-angle X-ray
      diffraction. Crystallographic texture can induce anisotropy in macroscopic
      properties of polymers, such as modulus and yield stress. Both rods and sheets of
      UHMWPE revealed a low but discernible degree of preferred orientation of
      polyethylene chains within crystallites. There was a spatial variation in
      crystallographic orientation in extruded rods. The direction of chain alignment
      within crystallites located near the outer surface of rods was orthogonal to the
      radial direction, whereas the chain direction was orthogonal to the axial or
      extrusion direction in crystallites located near the centreline of extruded rods.
      Crystallographic texture was spatially uniform in compression-moulded sheets with
      the chain direction within crystallites aligned orthogonal to the moulding
      direction. In both cases the induced crystallographic texture can be explained in
      terms of crystallization from an oriented melt.

PMID- 8982473
TI  - Influence of intraperitoneal injection of three types of hydrogel beads on
      expression of carbohydrate-binding sites in spleen macrophages.
AB  - The influence of the chemical structure of polymer implants on selected
      characteristics of macrophages was studied to improve our understanding of the
      mechanisms of non-self recognition of synthetic materials. Three types of
      polymers differing in net charge were prepared to compare in vivo responses.
      Beads from preparation of poly(2-hydroxyethyl methacrylate), a copolymer of 2
      hydroxyethyl methacrylate with sodium methacrylate, and a copolymer of 2
      hydroxyethyl methacrylate and dimethylaminoethyl methacrylate were injected
      intraperitoneally into rats and harvested 48 h later. The effects of these
      polymers on the presence of inflammatory cells in the peritoneal exudate, on the
      adhesion of macrophages to individual batches of the different types of beads and
      on distinct molecular aspects of macrophages in the red pulp of spleen were
      evaluated. Beads from both types of copolymer caused an elevation in the number
      of macrophages in the exudate, in contrast to the situation in rats treated with
      poly(2-hydroxyethyl methacrylate) beads and physiological saline solution as
      control. The molecular design of the implant had no significant influence on the
      extent of macrophage adhesion to beads or on the expression of selected
      carbohydrate-binding sites. Since important cellular functions such as cell
      adhesion and glycoprotein routing depend on the sugar part of glycoconjugates,
      labelled neoglycoproteins were employed to analyse this aspect of macrophages in
      the tested animals. The beads of the copolymer of 2-hydroxyethyl methacrylate
      with dimethylaminoethyl methacrylate clearly led to an elevation of the
      expression of specific binding sites for beta-galactoside-terminating structures
      which are presented by asialofetuin, for mannose, fucose, sialic acid and N
      acetylgalactosamine, which had been used as the ligand parts of biotinylated
      neoglycoproteins, in spleen macrophages whereas the levels of sites which
      recognize mannose-6-phosphate were unaffected. Expression of sites with
      specificity to N-acetylglucosamine was lessened. The effect of beads from the
      copolymer of 2-hydroxyethyl methacrylate with sodium methacrylate on the measured
      glycobiological features in the splenic macrophages was only negligible. These
      results suggest the possibility of systemic effects of implanted polymers on the
      distinct recognitive functions of macrophages.

PMID- 8982474
TI  - Macroporous poly(sucrose acrylate) hydrogel for controlled release of
      macromolecules.
AB  - We have studied the controlled release of proteins from poly(sucrose acrylate)
      hydrogels. The hydrogels were prepared by a two-step procedure in which sucrose
      was first acylated to sucrose-1'-acrylate followed by free radical
      polymerization. By adjusting the cross-link ratio and initial monomer
      concentration, the swelling ratio of the hydrogel was varied from five to 28. The
      mechanical strength of these hydrogels was comparable to that of the hydrogels
      with approximately the same swelling ratio. Scanning electron micrographs and
      mesh size calculations indicate that the hydrogel is macroporous, suggesting it
      may be suitable for a variety of biomedical applications. The release kinetics of
      beta-lactoglobulin, bovine serum albumin and gamma-globulin were studied as a
      function of initial monomer concentrations for the sucrose-based hydrogel. All of
      the release profiles were characterized by an initial burst of protein in the
      first 25 h followed by a long period of sustained release (> 500 h). The
      magnitude of the initial burst was reduced by increasing the initial monomer
      concentration and by increasing the molecular weight of the protein. A
      quantitative model based on the heterogeneous nature of hydrogel was developed to
      explain the observed release kinetics.

PMID- 8982475
TI  - Long-term in vivo performance and biocompatibility of poly(vinyl alcohol)
      hydrogel macrocapsules for hybrid-type artificial pancreas.
AB  - A bag-shaped macrocapsule suitable for Langerhans islets entrapment and
      immunoisolation was constructed using a semipermeable hydrogel membrane of
      poly(vinyl alcohol)(PVA) cross-linked chemically and sterilized by a radiation
      method. Empty (not seeded with Langerhans islets), sealed, sterile macrocapsules
      were implanted into the intraperitoneal cavity of adult female Buffalo rats for
      periods of up to 6.5 months. Long-term in vivo performance of the macrocapsule
      membrane was evaluated on the basis of the permeability measurements of glucose
      and albumin. The results of experiments revealed the progressive, disadvantageous
      alterations of the PVA hydrogel membrane resulting in a decrease in the
      permeability of solutes. Histochemical examinations of the cellular enzyme
      activities in the implant-encapsulating tissue, regarding the acid and alkaline
      phosphatases, were performed to evaluate the activity of cells involved in the
      inflammatory response to the long-term macrocapsule implantation.

PMID- 8982476
TI  - Physical properties of a porcine internal thoracic artery fixed with an epoxy
      compound.
AB  - This study aimed to investigate the physical properties of a porcine internal
      thoracic artery fixed with an epoxy compound. Fresh and glutaraldehyde-fixed
      porcine arteries were used as controls. Both the epoxy-fixed and glutaraldehyde
      fixed porcine arteries showed significant increases in fixation index and
      denaturation temperature as compared to the fresh one. Additionally, the
      resistance of porcine arteries against bacterial collagenase in vitro degradation
      increased significantly after cross-linking with the epoxy compound of
      glutaraldehyde. The reduction of the tensile strength of the epoxy-fixed artery
      after bacterial collagenase degradation was more severe than in its
      glutaraldehyde-fixed counterpart. Generally, with increasing pH, temperature or
      fixative concentration, the fixation indices and denaturation temperatures of the
      epoxy-fixed porcine arteries increased. The results obtained in this study may be
      used to optimize the fixation process for developing a small-diameter biological
      vascular graft fixed by an epoxy compound.

PMID- 8982477
TI  - Experimental assay of a Dual Mesh polytetrafluoroethylene prosthesis (non-porous
      on one side) in the repair of abdominal wall defects.
AB  - The porosity of the prosthetic biomaterials used to repair defects in the
      abdominal wall seems to influence the tissue repair process insofar as tissue
      integration of the prosthetic material and the formation of adhesions with
      abdominal viscera are concerned. We studied the behaviour of a new type of
      polytetrafluoroethylene prosthesis used for the repair of abdominal wall defects.
      Dual Mesh (DM), which has two different faces; one face has a porosity between 30
      and 60 microns, while the other is non-porous. In 20 New Zealand White rabbits, a
      full-thickness (except skin) 7 cm x 5 cm defect was created in the anterior
      abdominal wall that was repaired with DM. At 14, 30, 60 and 90 days, samples were
      obtained and studied by light and scanning electron microscopy. An
      immunohistochemical study was made with antibody anti-rabbit macrophages (RAM
      11). Tensile strength was measured with an Instron tensiometer using 2-cm-wide
      strips obtained parallel to the shorter axis of the implant. DM induced little
      tissue adhesion to the material on the visceral peritoneum interface and was
      surrounded by organized repair tissue. The biomaterial was integrated in the
      repair tissue on the subcutaneous interface, but not on the peritoneal interface.
      The macrophage response decreased between days 14 and 90 (P < 0.001). Tensile
      strength increased significantly (P < 0.05) at every study period. We conclude
      that the DM prosthesis has little tendency to formation of visceral adhesions,
      the DM prosthesis was well tolerated by the receptor organism and the tensile
      strength of the prosthesis/receptor tissue interface increased with time.

PMID- 8982478
TI  - Acidity near eroding polylactide-polyglycolide in vitro and in vivo in rabbit
      tibial bone chambers.
AB  - Eroding poly(DL-lactide-co-glycolide)(PDLLG) washers were observed chronically in
      vitro and in vivo following loading in a bone chamber tibial implant (BCI).
      Images were recorded using intravital microscopy of the implanted rabbit and
      direct pH measurements were obtained of the tissue in the bone chamber using a
      combination probe-reference microelectrode. While statistically significant pH
      differences were found between the control (unloaded) and experimental (PDLLG
      bearing) BCIs, they were only of the order of 0.2 pH units. This value proved to
      be physiologically insignificant as no statistically significant difference in
      bone defect healing, as indicated by angiogenesis, was detected. It was shown
      that the measured small pH changes during PDLLG washers erosion would result
      whether the buffer was phosphate-buffered saline replaced weekly or interstitial
      fluid subject to vascular exchanges.

PMID- 8982479
TI  - Elastase-induced hydrolysis of synthetic solid substrates: poly(ester-urea
      urethane) and poly(ether-urea-urethane).
AB  - Human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE) were
      incubated with two radiolabelled model poly(urethane), a poly(ester-urea
      urethane) containing [14C]toluene diisocyanate ([14C]TDI),
      poly(caprolactone)(PCL) and ethylenediamine (ED), and a poly(ether-urea-urethane)
      containing [14C]TDI, poly(tetramethylene oxide) (PTMO) and ED. Ten-fold more
      radioactive carbon was released when PPE was incubated with [14C]TDI/PCL/ED than
      when HNE was used. The PPE-induced radioactive carbon release was significantly
      reduced by a specific elastase inhibitor. Ten-fold less radioactive carbon was
      released when [14C]TDI/PTMO/ED was incubated with PPE as compared to
      [14C]TDI/PCL/ED. Since neutrophils, which contain elastolytic activity, are
      present during the inflammatory response, the stability of biomaterials used in
      implanted devices may be affected.

PMID- 8982480
TI  - Controversies in hyperlipidaemia: issues resolved?

PMID- 8982481
TI  - Post-traumatic stress counselling: benefit or indulgence?

PMID- 8982482
TI  - Investigation and management of acute diarrhoea.
AB  - Acute diarrhoea is a common but debilitating symptom with diverse aetiology. The
      aim of this review is to consider the important pathogens, diagnostic approaches
      and management of acute diarrhoea.

PMID- 8982483
TI  - Treatment of schizophrenia: advances during the decade of the brain.
AB  - In conferring the 1990s as the decade of the brain, clinicians and scientists
      have recognized schizophrenia as a priority disorder for the development of
      innovative therapies and the deployment of research resources. This article
      reviews the progress gained so far during this period which gives cause for
      optimism for better understanding and treatment of schizophrenia.

PMID- 8982484
TI  - Lyme borreliosis: an update.
AB  - Lyme borreliosis is now known to be associated with a variety of different
      genospecies of spirochaetes. The resulting clinical picture may vary according to
      which genospecies is causing the infection. Multiple infection with other agents
      may complicate the diagnosis.

PMID- 8982485
TI  - How to be an effective educational supervisor.

PMID- 8982486
TI  - Assessment of competence of trainees in the medical specialties.

PMID- 8982487
TI  - So you want to train in histopathology.

PMID- 8982488
TI  - So you want to train in anaesthetics.

PMID- 8982489
TI  - So you want to train in vascular surgery.

PMID- 8982491
TI  - Ageing in black and ethnic minorities: a challenge to service provision.
AB  - Health services should not be colour-blind or ethnicity-blind. Service providers
      need to be aware of any differences in need between ethnic groups as well as
      between genders, age groups, and so on. There will be a greatly increased number
      of older people among minority ethnic groups in Britain in the next 10-20 years.
      This article reviews some of the reasons why this is a challenge to the health
      and care services.

PMID- 8982490
TI  - Modern management of ectopic pregnancy.

PMID- 8982492
TI  - Methods for separation, electrophoresis and probing DNA and RNA.

PMID- 8982493
TI  - Research and development in the NHS.
AB  - Research and development is now a core function within the NHS. New funding
      arrangements are being introduced which will both broaden the providers involved
      but also make the whole process more explicit and accountable. These changes are
      likely to impact on all doctors.

PMID- 8982494
TI  - Interaction of biphenylimidazole and imidazoleacrylic acid nonpeptide antagonists
      with valine 108 in TM III of the AT1 angiotensin receptor.
AB  - Interspecies amino acid exchange, based on pharmacological differences between
      mammalian AT1 and amphibian xAT angiotensin II receptors, previously demonstrated
      that Val108 in transmembrane III (ValIII:08) is a critical structural requirement
      for binding the biphenylimidazole, losartan. Here, we investigated a series of
      biphenylimidazole and imidazoleacrylic acid nonpeptides to determine the general
      role of Val108 in nonpeptide recognition. Substitution of Val108 in the rAT1b
      receptor with Ile, the corresponding residue in xATa, significantly reduced
      ligand affinities from both nonpeptide classes (Fmut values (mutant
      IC50/rAT1bIC50): losartan > L-162,389 > L-16,313 > L-162,017 = L-163,491 > SB
      203,220 > SK&F-108,566). While distinct molecular requirements exist for
      biphenylimidazole and imidazoleacrylic acid binding, these results suggest that
      Val108 is a common structural determinant of nonpeptide recognition on the AT1
      receptor.

PMID- 8982495
TI  - Pharmacological characterization of the inwardly-rectifying current in the smooth
      muscle cells of the rat bladder.
AB  - 1. In freshly-isolated single cells of the rat bladder detrusor, outwardly
      rectifying and inwardly-rectifying membrane currents were identified by the whole
      cell voltage-clamp technique. 2. The inwardly-rectifying current (IIR) exhibited
      features of a cation current permeable to both K+ and Na+ but it was unaffected
      by changes in extracellular Ca2+. It had an activation threshold close to -60 mV
      and an estimated reversal potential of -29 mV. 3. IIR activated slowly with a
      voltage-sensitive time-constant of 69 ms at -140 mV and 209 ms at -100 mV but did
      not exhibit time-dependent inactivation. 4. IIR was unaffected by
      tetraethylammonium (up to 20 mM) but it was reduced by extracellular Ba2+ (1 mM)
      and by extracellular Cs+ (1 mM). 5. IIR was reduced by terikalant (100 microM)
      and markedly inhibited by ciclazindol (100 microM) although at these
      concentrations, both agents also reduced outward currents. 6. IIR was inhibited
      by ZD7288 (10-100 microM) in a concentration-dependent manner. At concentrations
      up to 30 microM, ZD7288 did not reduce the magnitude of outward currents but
      these were inhibited by 100 microM ZD7288. 7. In strips of bladder detrusor,
      spontaneous mechanical activity was increased by ZD7288 (0.3-100 microM) and by
      ciclazindol (0.3-100 microM) but was unaffected by glibenclamide (1-10 microM).
      8. It is concluded that IIR closely resembles the hyperpolarization-activated
      current Ih, previously described in the smooth muscle of rabbit jejunum and in a
      variety of other cell types. This current may play an important role in
      modulating detrusor excitability but this could not be confirmed using the
      inhibitors ZD7288 and ciclazindol.

PMID- 8982496
TI  - Inward transport of [3H]-1-methyl-4-phenylpyridinium in rat isolated hepatocytes:
      putative involvement of a P-glycoprotein transporter.
AB  - 1. The liver has an important role in the detoxification of organic cations from
      the circulation. [3H]-1-methyl-4-phenylpyridinium ([3H]-MPP+), a low molecular
      weight organic cation, is efficiently taken up and accumulated by rat hepatocytes
      through mechanisms partially unknown. 2. The aim of the present work was to
      characterize further the uptake of MPP+ by rat isolated hepatocytes. The putative
      interactions of a wide range of drugs, including inhibitors/substrates of P
      glycoprotein, were studied. 3. The uptake of MPP+ was investigated in rat freshly
      isolated hepatocytes (incubated in Krebs-Henseleit medium with 200 nM [3H]-MPP+
      for 5 min) and in the rat liver in situ (perfused with Krebs-Henseleit/BSA medium
      with 200 nM [3H]-MPP+ for 30 min). [3H]-MPP+ accumulation in the cells and in
      tissue was determined by liquid scintillation counting. 4. Verapamil (100
      microM), quinidine (100 microM), amiloride (1 mM), (+)-tubocurarine (100 microM),
      vecuronium (45 microM), bilirubin (200 microM), progesterone (200 microM),
      daunomycin (100 microM), vinblastine (100 microM), cyclosporin A (100 microM) and
      cimetidine (100 microM) had a significant inhibitory effect on the accumulation
      of [3H]-MPP+ in isolated hepatocytes. Tetraethylammonium (100 microM) had no
      effect. 5. In the rat perfused liver, both cyclosporin A (100 microM) and
      verapamil (100 microM) had much less marked inhibitory effects as compared to
      their effects on isolated hepatocytes (0% against 35% and 45% against 96% of
      inhibition, respectively). 6. Inhibition of alkaline phosphatase activity by
      increasing or decreasing the pH of the incubation medium or by the presence of
      vanadate (1 mM) or homoarginine (500 microM) led to a significant increase in the
      accumulation of [3H]-MPP+ in isolated hepatocytes. 7. It was concluded that, in
      addition to the type I organic cation hepatic transporter, [3H]-MPP+ is taken up
      by rat hepatocytes through P-glycoprotein, a canalicular transport system that
      usually excretes endobiotics and xenobiotics. We proposed that the reversal of
      transport through P-glycoprotein may be related to the loss of efficacy of
      alkaline in isolated hepatocytes.

PMID- 8982498
TI  - Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase.
AB  - 1. Dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes the
      endogenous nitric oxide synthase inhibitors NG-monomethyl-arginine and NG,NG
      dimethy-L-arginine to citrulline, was identified by Western blotting in rat and
      human tissue homogenates. 2. S-2-amino-4(3-methylguanidino)butanoic acid (4124W)
      inhibited the metabolism of [14C]-NG-monomethyl-L-arginine to [14C]-citrulline by
      rat liver homogenates (IC50 416 +/- 66 microM; n = 9), human cultured endothelial
      cells (IC50 250 +/- 34 microM; n = 9) and isolated purified dimethylarginine
      dimethylaminohydrolase. 3. Addition of 4124W to culture medium increased the
      accumulation of endogenously-generated NG,NG-dimethy-L-arginine in the
      supernatant of human cultured endothelial cells from 3.1 +/- 0.3 to 5 +/- 0.7
      microM (n = 15; P < 0.005). 4. 4124W (1 microM - 1 mM) had no direct effect on
      endothelial nitric oxide synthase activity but caused endothelium-dependent
      contraction of rat aortic rings (1 mM 4124W increased tone by 81.5 +/- 9.6% of
      that caused by phenylephrine 100 nM). This effect was reversed by L-arginine (100
      microM). 4124W reversed endothelium-dependent relaxation of human saphenous vein
      (19.2 +/- 6.7% reversal of bradykinin-induced relaxation at 1 mM 4124W). 5. These
      data suggest that inhibition of dimethylarginine dimethylaminohydrolase increases
      the intracellular contraction of NG,NG-dimethyl-L-arginine sufficiently to
      inhibit nitric oxide synthesis. Inhibiting the activity of DDAH may provide an
      alternative mechanism for inhibition of nitric oxide synthases and changes in the
      activity of DDAH could contribute to pathophysiological alterations in NO
      generation.

PMID- 8982497
TI  - Tachykinin inhibition of acid-induced gastric hyperaemia in the rat.
AB  - 1. Primary afferent neurones releasing the vasodilator, calcitonin gene-related
      peptide, mediate the gastric hyperaemic response to acid back-diffusion. The
      tachykinins neurokinin A (NKA) and substance P (SP) are located in the same
      neurones and are co-released with calcitonin gene-related peptide. In this study
      we investigated the effect and possible role of tachykinins in the acid-evoked
      gastric vasodilatation in urethane-anaesthetized rats. 2. Gastric acid back
      diffusion, induced by perfusing the stomach with 15% ethanol in the presence of
      0.05 M HCl, increased gastric mucosal blood flow by 60-90%, as determined by the
      hydrogen clearance technique. NKA and SP (0.14-3.78 nmol min-1 kg-1, infused
      intra-aortically) inhibited the gastric mucosal hyperaemic response to acid back
      diffusion in a dose-dependent manner, an effect that was accompanied by
      aggravation of ethanol/acid-induced macroscopic haemorrhagic lesions. 3. The
      inhibitory effect of NKA (1.26 nmol min-1 kg-1) on the acid-induced gastric
      mucosal vasodilatation was prevented by the tachykinin NK2 receptor antagonists,
      MEN 10,627 (200 nmol kg-1) but left unaltered by the NK1 receptor antagonist, SR
      140,333 (300 nmol kg-1) and the mast-cell stabilizer, ketotifen (4.6 mumol kg-1).
      4. Under basal conditions, with 0.05 M HCl being perfused through the stomach,
      NKA (1.26 nmol min-1 kg-1) reduced gastric mucosal blood flow by about 25%, an
      effect that was abolished by SR 140,333 but not MEN 10,627 or ketotifen. 5. SR
      140,333, MEN 10,627 or ketotifen had no significant effect on basal gastric
      mucosal blood flow nor did they modify the gastric mucosal hyperaemic reaction to
      acid back-diffusion. 6. The effect of NKA (1.26 nmol min-1 kg-1) in causing
      vasoconstriction and inhibiting the vasodilator response to acid back-diffusion
      was also seen when blood flow in the left gastric artery was measured with the
      ultrasonic transit time shift technique. 7. Arginine vasopressin (AVP, 0.1 nmol
      min-1 kg-1) induced gastric mucosal vasoconstriction under basal conditions but
      was unable to inhibit the dilator response to acid back-diffusion. 8. These data
      show that NKA has two fundamentally different effects on the gastric circulation.
      Firstly, NKA reduces gastric blood flow by activation of NK1 receptors. Secondly,
      NKA inhibits the gastric hyperaemic response to acid back-diffusion through an
      NK2 receptor-mediated mechanism. These two tachykinin effects appear to take
      place independently of each other since they are mediated by different receptors.
      This concept is further supported by the inability of AVP to mimic tachykinin
      inhibition of the gastric vasodilator response to acid back-diffusion.

PMID- 8982499
TI  - P2x-purinoceptors of myenteric neurones from the guinea-pig ileum and their
      unusual pharmacological properties.
AB  - 1. Whole-cell and outside-out patch clamp recordings were used to characterize
      the physiological and pharmacological properties of the P2x-purinoceptors of
      myenteric neurones from the guinea-pig ileum. 2. Adenosine 5'-triphosphate (ATP)
      and analogues (1-3000 microM) evoked a rapid inward current in > 90% of all
      recorded neurones. The reversal potential of this current was dependent on the
      extracellular sodium concentration, at +14 +/- 1.9, 0 +/- 1.6 and -12 +/- 1 mV
      for 166, 83 and 42 mM of sodium, respectively. The fast activation and
      inactivation of this current occurred even when guanosine 5'-triphosphate (GTP)
      was omitted from the pipette solution or substituted with an equimolar
      concentration of guanosine 5'-o-[2-thiotriphosphate] (GTP-gamma-S). Single
      channel currents were observed when these outside-out membrane patches were
      exposed to ATP (10-30 microM). These channels have a unitary conductance of about
      17 picosiemens. 3. The rank-order of potency of the agonists used to induce the
      whole-cell currents was: ATP-gamma-S = ATP = 2-methylthio-ATP (2-Me-S-ATP) > >
      alpha, beta-methylene ATP = beta, gamma-methylene ATP; adenosine and uridine 5'
      triphosphate (UTP) (up to 1 mM) were inactive. 4. Pyridoxalphosphate-6-azophenyl
      2',4'-disulphonic acid (PPADS) (1-30 microM) antagonized the effects of ATP (1
      mM) with an IC50 of 4 microM. alpha, beta-Methylene ATP (100 microM) did not
      affect the ATP (30 microM)-induced current. Cibacron Blue 3GA increased the ATP
      activated cationic current whereas Basilen Blue E-3G had a very weak antagonistic
      effect (IC50 > or = 3 mM). Suramin potentiated the currents induced by ATP
      through a mechanism that was independent of its inhibitory effect on
      ectonucleotidase activity, as suramin also potentiated the effect of alpha, beta
      methylene ATP (an ATP analogue that is resistant to nucleotidases). 5. In
      conclusion, the myenteric P2x-purinoceptor shares some properties with other
      purinoceptors in particular with the P2x4- and P2x6-purinoceptors. This receptor
      has also some unusual pharmacological properties suggesting that myenteric
      neurones express a novel subtype of P2x-purinoceptors. The properties of this
      receptor, however, might be a result of the combination of two or more of the
      homomeric purinoceptors so far characterized.

PMID- 8982500
TI  - Analysis of relaxation and repolarization mechanisms of nicorandil in rat
      mesenteric artery.
AB  - 1. The mechanisms by which nicorandil causes relaxation of rat isolated small
      mesenteric arteries mounted on a Mulvany myograph was investigated by use of a
      combination of putatively mechanism-specific antagonists. 2. In arteries
      precontracted by the thromboxane-mimetic, U46619, the EC50 for cromakalim and
      levcromakalim-induced relaxation curves were raised by 36 and 17 fold by
      glibenclamide (3 microM) while the EC50 for nicorandil-induced relaxation was
      unaffected by either glibenclamide or methylene blue (10 microM). A combination
      of these antagonists raised the EC50 for nicorandil by 8 fold. 3. In U46619
      contracted arteries, nifedipine (100 nM) did not affect the cromakalim relaxation
      curve but it raised the EC50 for nicorandil by 5 fold. The combination of
      methylene blue, glibenclamide and nifedipine further inhibited the maximum
      relaxation to nicorandil. 4. In separate experiments, membrane potential (Em) and
      force responses were measured simultaneously. In arteries depolarized and
      contracted by U46619 both nicorandil and cromakalim repolarized (delta Em, 35 mV)
      and relaxed (100%) the vessels. Glibenclamide (3 microM) did not alter the
      relaxation-concentration curve to nicorandil but reduced the maximum
      repolarization to delta 10.8 mV. In contrast to Em and relaxation-response curves
      to cromakalim were shifted to the right by glibenclamide by 30-100 fold. 5. In
      unstimulated arteries, nicorandil (but not cromakalim) -induced hyperpolarization
      was significantly antagonized by methylene blue (10 microM) (6.6 fold rightward
      shift) or nifedipine (100 nM) (2.6 fold). In depolarized arteries (U46619),
      nifedipine but not methylene blue inhibited the nicorandil-induced
      hyperpolarization. 6. In arteries precontracted to 50% tissue maximum by either
      KCl or U46619, nifedipine (100 nM) relaxed the artery but failed to repolarize
      the Em. Presumably voltage-operated calcium channels (VOCC) were blocked
      preventing contraction but the artery remained depolarized, presumably through
      non VOCC mechanisms. 7. These data suggest that nicorandil may relax small
      arteries through 3 parallel pathways, (i) NO-donor mediated stimulation of
      guanylate cyclase and increase in cyclic GMP, (ii) K+ATP channel opening, and
      (iii) nifedipine-sensitive VOCC inhibition. Em data suggest that nicorandil
      induced repolarization is caused principally through opening K+ATP channels.
      Blockade of this hyperpolarization by glibenclamide is not sufficient to alter
      the relaxation, indicating dissociation of nicorandil-induced changes in membrane
      potential and relaxation. 8. These results highlight the 'chameleon' actions of
      nicorandil where there is no apparent association of Em repolarization with
      relaxation, in contrast to the parallel responses for cromakalim.

PMID- 8982501
TI  - Evidence that potassium channels make a major contribution to SIN-1-evoked
      relaxation of rat isolated mesenteric artery.
AB  - 1. The NO donor 3-morpholino-sydnonimine (SIN-1; 0.01-10 microM) evoked
      concentration-dependent relaxation of rat isolated mesenteric arteries pre
      constricted with phenylephrine (1-3 microM). The relaxation to SIN-1 was not
      significantly different between endothelium-intact or denuded arterial segments
      or segments in which basal nitric oxide (NO) synthesis was inhibited (n = 8; P >
      0.05). In contrast, the membrane permeable analogue of guanosine 3':5'-cyclic
      monophosphate (cyclic GMP), 8-Br-cyclic GMP (0.01-1 mM), was much less effective
      in relaxing intact than denuded arterial segments or intact arterial segments pre
      incubated with NO synthase blockers (n = 4; P < 0.01). 2. 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM; 10 min) alone, did not
      alter SIN-1-evoked relaxation in any tissues (n = 5; P > 0.05). However, in
      parallel experiments, ODQ almost completely inhibited both basal and SIN-1
      stimulated production of cyclic GMP in both the presence and absence of NO
      synthase blockers (n = 6; P < 0.01) indicating that full relaxation to SIN-1 can
      be achieved in the absence of an increase in cyclic GMP. 3. Exposure of
      endothelium-intact arterial segments to the potassium channel blocker
      charybdotoxin (50 nM; 10 min), significantly inhibited SIN-1-evoked relaxation,
      reducing the maximum response by around 90% (n = 5; P < 0.01). In contrast, in
      arterial segments in which either the endothelial cell layer had been removed or
      basal NO synthesis inhibited, relaxation to SIN-1 was not reduced in the presence
      of charybdotoxin (n = 6; P > 0.05). However, in the presence of NO synthase
      blockers and L-arginine (300 microM) together, charybdotoxin did significantly
      inhibit SIN-1-evoked relaxation to a similar extent as intact tissues (maximum
      response induced by around 80%; n = 4; P < 0.01). 4. Pre-incubation with apamin
      (30 nM; 10 min) or glibenclamide (10 microM; 10 min) did not alter SIN-1-evoked
      relaxation of phenylephrine-induced tone in any tissues (n = 4 and n = 6,
      respectively; P > 0.05). However, in the presence of either ODQ and apamin, or
      ODQ and glibenclamide, SIN-1-evoked relaxation was significantly attenuated in
      intact arterial segments and segments in which NO synthesis was blocked. 5.
      Exposure of intact arterial segments to charybdotoxin and apamin, in the presence
      of NO synthase blockers, also significantly inhibited SIN-1-evoked relaxation,
      reducing the maximum response by around 80% (n = 4; P < 0.01). 6. Addition of
      superoxide dismutase (SOD; 30 u ml-1), potentiated relaxations to SIN-1 in all
      tissues, but did not alter the effects of charybdotoxin and ODQ and SIN-1-evoked
      relaxation. 7. These data show that although relaxation to the NO-donor SIN-1 is
      not significantly different between endothelium-intact and denuded arterial
      segments, the mechanisms which mediate SIN-1-evoked relaxation in the rat
      isolated mesenteric artery appear to be modulated by the basal release of
      endothelium-derived NO. In the presence of an intact endothelial cell layer, the
      major mechanism for SIN-1-evoked relaxation appears to be the activation of
      charybdotoxin-sensitive potassium channels. In contrast, when basal NO synthesis
      is inhibited, SIN-1 appears to cause full relaxation by both the activation of a
      charybdotoxin-sensitive pathway and the stimulation of soluble guanylyl cyclase.

PMID- 8982502
TI  - A possible structural determinant of selectivity of boldine and derivatives for
      the alpha 1A-adrenoceptor subtype.
AB  - 1. The selectivity of action of boldine and the related aporphine alkaloids,
      predicentrine (9-O-methylboldine) and glaucine (2,9-O-dimethylboldine) and alpha
      1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition
      binding in rat cerebral cortex. WB 4101 and benoxathian were used as selective
      alpha 1A-adrenoceptor antagonists. 2. In the competition experiments [3H]
      prazosin (0.2 nM) binding was inhibited by WB 4101 and benoxathian. The
      inhibition curves displayed shallow slopes which could be subdivided into high
      and low affinity components (pKi = 9.92 and 8.29 for WB 4101, 9.35 and 7.94 for
      benoxathian). The two antagonists recognized approximately 37% of the sites with
      high affinity from among the total [3H]-prazosin specific binding sites. 3.
      Boldine, predicentrine and glaucine also competed for [3H]-prazosin (0.2 nM)
      binding with shallow and biphasic curves recognizing 30-40% of the sites with
      high affinity. Drug affinities (pKi) at the high and low affinity sites were,
      8.31 and 6.50, respectively, for boldine, 8.13 and 6.39 for predicentrine, and
      7.12 and 5.92 for glaucine. The relative order of selectivity for alpha 1A
      adrenoceptors was boldine (70 fold alpha 1A-selective) = predicentrine (60 fold,
      alpha 1A-selective) > glaucine (15 fold, alpha 1A-selective). 4. Pretreatment of
      rat cerebral cortex membranes with chloroethylclonidine (CEC, 10 microM) for 30
      min at 37 degrees C followed by thorough washing out reduced specific [3H]
      prazosin binding by approximately 70%. The CEC-insensitive [3H]-prazosin binding
      was inhibited by boldine monophasically (Hill slope = 0.93) with a single pKi
      value (7.76). 5. These results suggest that whereas the aporphine structure
      shared by these alkaloids is responsible for their selectively of action for the
      alpha 1A-adrenoceptor subtype in rat cerebral cortex, defined functional groups,
      namely the 2-hydroxy function, induces a significant increase in alpha 1A-subtype
      selectivity and affinity.

PMID- 8982503
TI  - Actions of picrodendrin antagonists on dieldrin-sensitive and -resistant
      Drosophila GABA receptors.
AB  - 1. A series of terpenoid compounds, recently isolated from Picrodendron baccatum,
      share a picrotoxane skeleton with picrotoxinin, an antagonist of ionotropic GABA
      receptors. Referred to as picrodendrins, they inhibit the binding of [35S]-tert
      butylbicyclophosphorothionate (TBPS) to rat GABAA receptors. Hitherto, their
      effects on GABA receptors have not been investigated electrophysiologically.
      Under two-electrode voltage-clamp, the actions of picrodendrins and related
      terpenoids have been assayed on homooligomeric GABA receptors formed by the
      expression of a Drosophila GABA receptor subunit (RDLac) in Xenopus oocytes. 2.
      All the terpenoids tested, dose-dependently antagonized currents induced by 30
      microM (EC50) GABA. 3. Tutin and its analogues (dihydrotutin and isohyenanchin)
      differ in the structure of their axial C4 substituents. Of these compounds,
      tutin, which bears an isopropenyl group at this carbon atom, was the most potent
      antagonist of RDLac homo-oligomers, whereas isohyenanchin, which bears a
      hydroxyisopropyl group, was the least potent antagonist tested. 4. Picrodendrins
      differ mainly in the structure of their C9 substituents. The IC50s of
      picrodendrins ranged from 17 +/- 1.3 nM (picrodendrin-Q) to 1006 +/- 1.3 nM
      (picrodendrin-O). As such, the most potent picrodendrins (Q, A and B) were
      approximately equipotent with picrotoxinin as antagonists of RDLac homo
      oligomers. 5. Certain picrodendrin compounds effected a use-dependent blockade of
      RDLac homo-oligomers. Such a biphasic block was not observed with tutin
      analogues. 6. Picrotoxin-resistant RDLacA3025 homo-oligomers, which have a single
      amino acid substitution (A302S) in the 2nd transmembrane region, were markedly
      less sensitive to picrodendrin-O than the wild-type, dieldrin-sensitive, homo
      oligomers. 7. The relative potency of tutin analogues demonstrates that the
      structure-activity relationship of the C4 substituent of picrotoxane-based
      compounds is conserved in vertebrates and insects. However, the relative order of
      potency of picrodendrins on RDLac homo-oligomers is distinctly different from
      that observed in previous radioligand binding studies performed on vertebrate
      GABAA receptors. As picrodendrin compounds differ in the structure of their C9
      substituents, these data suggest that the optimal convulsant pharmacophores of
      vertebrate GABAA receptors and RDLac homo-oligomers differ with respect to this
      substituent.

PMID- 8982504
TI  - Agonist pharmacology of two Drosophila GABA receptor splice variants.
AB  - 1. The Drosophila melanogaster gamma-aminobutyric acid (GABA) receptor subunits,
      RDLac and DRC 17-1-2, form functional homo-oligomeric receptors when
      heterologously expressed in Xenopus laevis oocytes. The subunits differ in only
      17 amino acids, principally in regions of the N-terminal domain which determine
      agonist pharmacology in vertebrate ionotropic neurotransmitter receptors. A range
      of conformationally restricted GABA analogues were tested on the two homo
      oligomers and their agonists pharmacology compared with that of insect and
      vertebrate iontropic GABA receptors. 2. The actions of GABA, isoguvacine and
      isonipecotic acid on RDLac and DRC 17-1-2 homo-oligomers were compared, by use of
      two-electrode voltage-clamp. All three compounds were full agonists of both
      receptors, but were 4-6 fold less potent agonists of DRC 17-1-2 homo-oligomers
      than of RDLac. However, the relative potencies of these agonists on each receptor
      were very similar. 3. A more complete agonist profile was established for RDLac
      homo-oligomers. The most potent agonists of these receptors were GABA, muscimol
      and trans-aminocrotonic acid (TACA), which were approximately equipotent. RDLac
      homo-oligomers were fully activated by a range of GABA analogues, with the order
      of potency: GABA > ZAPA ((Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid) >
      isoguvacine > imidazole-4-acetic acid > or = isonipecotic acid > or = cis
      aminocrotonic acid (CACA) > beta-alanine. 3-Aminopropane sulphonic acid (3-APS),
      a partial agonist of RDLac homo-oligomers, was the weakest agonist tested and 100
      fold less potent than GABA. 4. SR95531, an antagonist of vertebrate GABAA
      receptors, competitively inhibited the GABA responses of RDLac homo-oligomers,
      which have previously been found to insensitive to bicuculline. However, its
      potency (IC50 500 microM) was much reduced when compared to GABAA receptors. 5.
      The agonist pharmacology of Drosophila RDLac homo-oligomers exhibits aspects of
      the characteristic pharmacology of certain native insect GABA receptors which
      distinguish them from vertebrate GABA receptors. The high potency and efficacy of
      isoguvacine and ZAPA distinguishes RDLac homo-oligomers from bicuculline
      insensitive vertebrate GABAC receptors, while the low potency of SR95531 and 3
      APS distinguishes them from GABAA receptors. The differences in the potency of
      agonists on RDLac and DRC 17-1-2 homo-oligomers observed in the present study may
      assist in identification of further molecular determinants of GABA receptor
      function.

PMID- 8982505
TI  - Effects of competitive and noncompetitive antagonists of the N-methyl-D-aspartate
      receptor on the analgesic action of delta 1- and delta 2-opioid receptor agonists
      in mice.
AB  - 1. The effects of MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate
      (NMDA) receptor and LY 235959, a competitive antagonists of the NMDA receptor on
      the analgesic actions of [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2, Glu4]
      deltorphin II (deltorphin II), the putative delta 1- and delta 2-opioid receptor
      agonists, respectively, were determined in the male Swiss-Webster mice. 2.
      Intracerebroventricular administration of DPDPE or deltorphin II produced
      analgesia. MK-801 administered intraperitoneally 10 min before the injection of
      DPDPE or deltorphin II, dose-dependently antagonized the analgesic actions of
      both drugs. 3. LY 235959 also dose-dependently antagonized the analgesic actions
      of DPDPE and deltorphin II. 4. The effects of MK-801 and LY 235959 on the binding
      of [3H]-DPDPE to mouse brain membranes were also determined. Neither of the NMDA
      receptor antagonists had any effect on the binding of [3H]-DPDPE. 5. It is
      concluded that competitive and noncompetitive antagonists of the NMDA receptor
      antagonize the analgesic action of delta 1- and delta 2-opioid receptor agonists
      and that such effects are not mediated via a direct interaction with brain delta
      opioid receptors.

PMID- 8982506
TI  - A cyclic GMP-dependent housekeeping Cl- channel in rabbit gastric parietal cells
      activated by a vasodilator ecabapide.
AB  - 1. The membrane potential of rabbit gastric parietal cells is dominated by a Cl-
      channel with a subpicosiemens single channel conductance in the basolateral
      membrane. The effects of 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]amino-N
      methylbenzamide++ + (DQ-2511: ecabapide), a vasodilator, on the opening of this
      Cl-1 channel, the cyclic GMP content and the intracellular free Ca2+
      concentration ([Ca2+]i) of parietal cells were investigated by whole-cell patch
      clamp technique, enzyme immunoassay and Fura 2-fluorescence measurement. 2.
      Ecabapide stimulated the opening of the Cl-1 channel as determined by the
      reversal potential. This stimulation was concentration-dependent, and its EC50
      value was 0.2 microM. Both the basal and ecabapide-induced openings of the
      channel were inhibited by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB, 500
      microM), a Cl- channel blocker. Another Cl- channel blocker, niflumic acid (500
      microM) was much less effective. 3. The power spectra of the currents before and
      after the addition of ecabapide (10 microM) were analysed. Both spectra contained
      only one Lorentzian (1/f2) component. 4. 6-Anilino-5,8-quinolinedione (LY83583; 5
      microM) which prevents activation of soluble guanylate cyclase, significantly
      inhibited both the basal and ecabapide (10 microM)-induced openings of the Cl-
      channel. 5. Ecabapide (0.01-100 microM) concentration-dependently elevated the
      cyclic GMP content in the parietal cell-rich suspension. The EC50 value was 0.2
      microM. 6. In single Fura 2-loaded parietal cells, ecabapide (10-100 microM) did
      not increase [Ca2+]i. 7. These results indicate that ecabapide stimulates an
      intracellular production of cyclic GMP in the parietal cell without increasing
      [Ca2+]i, and leads to an activation of the housekeeping Cl- channel.

PMID- 8982507
TI  - Characterization of endothelin receptors in the human umbilical artery and vein.
AB  - The aim of the present study was to characterize pharmacologically endothelin
      receptors that are present in human umbilical vessels. 2. Endothelin-1 (ET-1) and
      endothelin-2 (ET-2) are potent stimulants of both the human umbilical artery
      (pEC50 7.9 and 7.5) and vein (pEC50 8.1 and 8.0). Endothelin-3 (ET-3) is inactive
      on the artery but contracts the vein (pEC50 7.6). IRL1620 is inactive in both
      vessels. The order of potency of agonists is suggestive of a typical ET(A)
      receptor in the artery (ET-1 = ET-2 > > ET-3) and a mixture of ET(A) and ET(B)
      receptors in the vein (ET-1 = ET-2 > or = ET-3). 3. The selective ET(A) receptor
      antagonist, BQ123, competitively inhibits the effect of ET-1 in the human
      umbilical artery (pA2 6.9), while in the vein, only a mixture of BQ123 and BQ788
      (a selective ET(B) antagonist) weakly displaces to the right of the cumulative
      concentration-response curve to ET-1. Contractions induced by ET-3 in the vein
      are inhibited by BQ788 (pA2 7.6), but not by BQ123. 4. Inhibition of Ca2+
      channels by nifedipine (0.1 microM) is accompanied by a significant decrease of
      the maximal response to ET-1 by 40% in the artery and by 30% in the vein. The
      response of the vein to ET-3 is almost abolished by nifedipine. 5. The results
      indicate that: (i) endothelins contract the human isolated umbilical artery via
      stimulation of an ET(A) receptor type; (ii) the contraction induced by ET-1 in
      the vein is mediated by both ET(A) and ET(B) receptors, while ET-3 stimulates the
      ET(B) receptor; (iii) the contribution of Ca2+ channels to the contraction
      mediated by the ET(B) receptor appears to be more important than to that mediated
      by the ET(A) receptor.

PMID- 8982508
TI  - Noradrenaline synthesis after sympathetic nerve activation in rat atria and its
      dependence on calcium but not CAM kinase II and protein kinases A or C.
AB  - 1. The biosynthesis of noradrenaline following sympathetic nerve activation was
      investigated in rat atria. In particular the time course of noradrenaline
      synthesis changes, the relationship of changes in synthesis to transmitter
      release and the possible roles of second messengers and protein kinases were
      examined. 2. Rat atria incubated with the precursor [3H]-tyrosine synthesized
      [3H]-noradrenaline. Synthesis was enhanced following pulsatile electrical field
      stimulation (3 Hz for 5 min) with the bulk of the increase occurring in the first
      45 min after the commencement of electrical stimulation. In separate experiments
      rat atria were pre-incubated with [3H]-noradrenaline and the radioactive outflow
      in response to electrical field stimulation (3 Hz for 5 min) was taken as an
      index of noradrenaline release. 3. Stimulation-induced (S-I) noradrenaline
      synthesis was significantly correlated to S-I noradrenaline release for a variety
      of procedures which modulate noradrenaline release by mechanisms altering Ca2+
      entry into the neurone (r2 = 0.99): those which decreased release: tetrodotoxin
      (0.3 microM), Ca(2+)-free medium, lowering the frequency of nerve activation to 1
      Hz, and those which increased release, tetraethylammonium (0.3 mM), phentolamine
      (1 microM) and the combination of phentolamine (1 microM) and adenosine (10
      microM). On the strength of this relationship we suggest that Ca2+ entry is a
      determining factor in S-I synthesis changes rather than the amount of
      noradrenaline released. Indeed the reduction in noradrenaline release with the
      calmodulin-dependent protein (CAM) kinase II inhibitor KN-62 (10 microM) which
      acts subsequent to Ca2+ entry, did not affect S-I synthesis. 4. The cell
      permeable cyclic AMP analogue, 8-bromoadenosine 3',5'-monophosphate (BrcAMP, 90
      and 270 microM), dose-dependently increased basal [3H]-noradrenaline synthesis in
      unstimulated rat atria. This effect was antagonized by the selective protein
      kinase A (PKA) antagonist, Rp-8-chloroadenosine 3',5'-cyclic monophosphorothioate
      (RClcAMPS, 300 microM), suggesting that PKA activation enhances basal
      noradrenaline biosynthesis in sympathetic nerve terminals. 5. The protein kinase
      inhibitors, KN-62 (CAM kinase II, 10 microM), RClcAMPS (PKA, 300 microM),
      polymyxin B (protein kinase C (PKC), 21 microM) and staurosporine (PKC, PKA and
      CAM kinase II, (0.1 microM) did not affect S-I synthesis, although KN-62,
      polymyxin B and staurosporine decreased S-I release. We conclude that S-I
      synthesis is triggered by Ca2+ entering the neurone but that the signalling
      pathway does not involve classical protein kinases and appears distinct from the
      steps involved in transmitter release.

PMID- 8982509
TI  - Nociceptin receptor coupling to a potassium conductance in rat locus coeruleus
      neurones in vitro.
AB  - 1. In this study we have examined the effects of nociceptin, an endogenous ligand
      for the opioid-like receptor ORL1 on the membrane properties of rat locus
      coeruleus (LC) neurones in vitro, using intracellular and whole cell patch clamp
      recording. 2. When locus coeruleus neurones were voltage clamped to -60 mV,
      application to nociceptin caused an outward current in all cells examined (n =
      49), with an EC50 of 90 nM. Neither the potency nor the maximal effect of
      nociceptin was altered in the presence of the peptidase inhibitors, bestatin (20
      microM) or thiorphan (2 microM). 3. The outward currents caused by nociceptin in
      2.5 mM extracellular K+ reversed polarity at -123 mV, more negative than the
      predicted K+ reversal potential of -105 mV. Increasing extracellular K+ to 6.5 mM
      resulted in a shift of the reversal potential of +25 mV, a shift consistent with
      a K+ conductance. The conductance activated by nociceptin showed mild inward
      rectification. 4. Application of a high concentration of nociceptin (3 microM)
      occluded the current produced by simultaneous application of high concentrations
      of Met-enkephalin (10 microM), (3 microM) somatostatin and UK 14304 (3 microM),
      indicating that nociceptin activated the same conductance as mu-opioid and
      somatostatin receptors and alpha 2-adrenoceptors. 5. The actions of nociceptin
      were weakly antagonized by the opioid antagonist, naloxone, with pKb's estimated
      from 2 cells of -4.23 and -4.33. The mu-opioid antagonist, CTAP (D-Phe-Cys-Tyr-D
      Trp-Arg-Pen-Thr-NH2, 1 microM), the opioid antagonist, nalorphine (30 microM) or
      the somatostatin antagonist, CPP (cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bz1])
      3 microM) did not affect the nociceptin-induced current. 6. Dynorphin A (microM),
      another putative endogenous ligand for ORL1, caused a robust outward current in
      locus coeruleus neurones that was, however, completely antagonized by moderate
      concentrations of naloxone (300 nM-1 microM). 7. Continuous application of
      nociceptin (3 microM) resulted in a decrease of the outward current to a steady
      level of 70% of the maximum response with a t1/2 of 120s. Desensitization was
      largely homologous because simultaneous application of Met-enkephalin (30 microM)
      during the desensitized period of the nociceptin response resulted in an outward
      current that was 92% of control responses to Met-enkephalin in the same cells.
      Conversely, continuous application of Met-enkephalin (30 microM) resulted in a
      decrease of Met-enkephalin current to a steady level that was 54% of the initial
      current. During this desensitized period application of nociceptin (3 microM)
      resulted in a current that was 78% of the control responses to nociceptin in the
      same cells. 8. Thus nociceptin potently activates an inwardly rectifying K+
      conductance in locus coeruleus neurones, with a pharmacological profile
      consistent with activation of the ORL1 receptor. Dynorphin A does not appear to
      be a ligand for ORL1 in rat locus coeruleus neurones.

PMID- 8982510
TI  - Temporal differences between the involvement of angiotensin II and endothelin in
      the cardiovascular responses to endotoxaemia in conscious rats.
AB  - 1. Male, Long Evans rats were instrumented chronically with pulsed Doppler probes
      and intravascular catheters to allow assessment of regional haemodynamic changes
      during i.v. infusion of lipopolysaccharide (LPS, 150 micrograms kg-1 h-1). 2. In
      the presence of the AT1-receptor antagonists, losartan (10 mg kg-1 + 10 kg-1 h
      1), the initial (1-2 h) hypotensive and renal, mesenteric and hindquarters
      vasodilator responses to LPS were enhanced significantly. Thereafter these
      effects waned, but between 8-23 h after the onset of LPS infusion, a further fall
      in mean atrial blood pressure (MAP) and increases in renal and hindquarters flows
      and conductances occurred. All these changes were significantly greater than seen
      with losartan or LPS alone, and exceeded the sum of their effects. 3. In the
      presence of captopril (2 mg kg-1 + 2 mg kg-1 h-1), the initial hypotensive and
      renal vasodilator responses to LPS were enhanced, but less so than in the
      presence of losartan. However, the effects of LPS in the presence of losartan and
      captopril together were not different from those in the presence of losartan
      alone. These observations indicate that the ability of captopril to inhibit the
      degradation of bradykinin had no additional influence, and the differences
      between the effect of captopril and losartan on the initial effects of LPS were
      probably due to more effective suppression of the action of angiotensin II by
      losartan. 4. In the absence of LPS, co-infusion of losartan and the non-selective
      endothelin antagonist, SB 209670 (600 micrograms kg-1 + 600 micrograms kg-1 h-1),
      caused a substantial, progressive hypotension (-25 +/- 2 mmHg at 24 h)
      accompanied by increases in renal, mesenteric and hindquarters vascular
      conductances (31 +/- 13, 44 +/- 9 and 45 +/- 12%, respectively), indicating an
      involvement of angiotensin II and endothelin in the maintenance of normal
      cardiovascular status in conscious, Long Evans rats. 5. In the presence of
      losartan and SB 209670, the initial, LPS-induced fall in MAP (-42 +/- 2 mmHg) was
      not different from that in the presence of losartan (-39 +/- 4 mmHg), and the
      increases in renal, in mesenteric, and in hindquarters vascular conductances were
      similar in the two conditions. However, there was no recovery in MAP, and there
      were persistent renal, mesenteric and hindquarter vasodilatations. 6. In all
      experiments involving LPS, administration of the V1- receptor antagonist, d(CH2)5
      O-Me-Tyr-AVP (10 micrograms kg-1), 23 h after the start of LPS infusion caused
      additional hypotension and mesenteric vasodilatation, particularly. This effect
      was most marked in animals pretreated with losartan and SB 209670. 7. The results
      indicate that the initial (1-2 h) depressor and dilator effects of LPS infusion
      in conscious Long Evans rats are opposed by the actions of angiotensins II,
      rather than endothelin. However, between 2-8 h after the onset of LPS infusion
      the involvement of endothelin develops and that of angiotensin II fades. By 24 h
      after the start of infusion of LPS, the pressor and vasoconstrictor actions of
      endothelin wane, and a role of vasopressin is apparent. At no stage is there
      clear evidence for an involvement of bradykinin in the haemodynamic sequelae of
      endotoxaemia in this model.

PMID- 8982511
TI  - Inhibition of ecto-ATPase by PPADS, suramin and reactive blue in endothelial
      cells, C6 glioma cells and RAW 264.7 macrophages.
AB  - 1. Previous studies have shown that bovine pulmonary artery endothelium (CPAE)
      has P2Y and P2U purinoceptors, rat C6 glioma cells have P2U purinoceptors and
      mouse RAW 264.7 cells have pyrimidinoceptors, all of which are coupled to
      phosphoinositide-specific phospholipase C (PI-PLC). The dual actions of PPADS,
      suramin and reactive blue as antagonists of receptor subtypes and ecto-ATPase
      inhibitors were studied in these three cell types. 2. In CPAE, suramin, at 3-100
      microM, competitively inhibited the PI responses induced by 2MeSATP and UTP, with
      pA2 values of 5.5 +/- 0.3 and 4.4 +/- 0.4, respectively. Reactive blue, at 1-3
      microM, produced shifts to the right of the 2MeSATP and UTP curves, but no
      further right shift at 10 microM. PPADS, at 10 microM, caused a 3 fold right
      shift of the 2MeSATP curve, but no further shift at concentrations up to 100
      microM. In contrast, a dose-dependent shift to the left of the UTP curve and a
      weak inhibition of the ATP response were seen with PPADS. 3. In RAW 264.7 cells,
      suramin and reactive blue, but not PPADS, competitively inhibited the UTP
      response, with pA2 values of 4.8 +/- 0.5 and 5.8 +/- 0.7, respectively. 4. In C6
      glioma cells, although suramin and reactive blue inhibited the ATP response, a
      potentiation effect on ATP and UTP responses was seen with PPADS. 5. The ecto
      ATPase inhibitory activity of these three receptor antagonists were determined.
      All three inhibited ecto-ATPase present in CPAE, C6 and RAW 264.7 cells, with
      IC50 values of 4, 4.8 and 4.7 for PPADS, 4, 4.4 and > > 4 for suramin, and 4.5,
      4.7 and 4.7 for reactive blue. 6. This study indicates that PPADS, suramin and
      reactive blue ar ecto-ATPase inhibitors. This property, combined with their
      antagonistic selectivity for receptor subtypes, can result in inhibition of,
      potentiation of, or lack of effect on agonist-mediated PI responses. Reactive
      blue is a more potent antagonist than suramin on P2Y, P2U and pyrimidinoceptors,
      and PPADS is a weak antagonist for P2Y receptors.

PMID- 8982512
TI  - Alterations of cyclo-oxygenase products and NO in responses to angiotensin II of
      resistance arteries from the spontaneously hypertensive rat.
AB  - 1. The involvement of cyclo-oxygenase (COX) products and nitric oxide (NO) in
      contractile responses of resistance arteries to angiotensin II (AII) were
      investigated in small mesenteric arteries from spontaneously hypertensive rats
      (SHR) and Wistar Kyoto (WKY) rats. 2. In endothelium intact vessels, AII induced
      concentration-dependent responses without any significant difference between the
      two strains. However, removal of functional endothelium resulted in enhanced
      sensitivity to AII, the pD2 value increasing from 8.4 +/- 0.2 to 8.9 +/- 0.2 (P <
      0.05) in WKY and from 8.2 +/- 0.1 to 8.6 +/- 0.1 (P < 0.05) in SHR (not
      significantly different between strains, n = 9 - 12). In addition, endothelium
      removal enhanced maximal contractions elicited by AII in SHR (1.4 +/- 0.1 to 2.1
      +/- 0.2 mN mm-1, n = 5; P < 0.05) but not in WKY (1.0 +/- 0.1 to 1.2 +/- 0.1 mN
      mm-1, n = 5) vessels. 3. In the absence of functional endothelium, the COX
      inhibitor indomethacin (10(-5) M) reduced contractile responses elicited by AII
      in SHR arteries, resulting in 33 +/- 5% (n = 5) decrease in maximal contraction.
      However, it produced minimal if any, effect on responses of WKY vessels. In both
      strains, the TP receptor antagonist GR32191 B (3 x 10(-6) M) did not modify
      contractions elicited by AII in these conditions. 4. In the presence of
      functional endothelium, indomethacin (10(-5) M) almost abolished the responses to
      AII in both strains. GR32191 B (3 x 10(-6) M) reduced the sensitivity of WKY
      arteries to AII (pD2 = 8.1 +/- 0.1, P < 0.01) without any effect on maximal
      contraction. In SHR arteries, it markedly reduced maximal contraction (47 +/-
      3.5%). 5. In both strains, the NO synthase inhibitor NG-nitro-L-arginine methy
      lester (L-NAME; 10(-4) M) had no effect in the absence of functional endothelium
      but it markedly reduced the inhibitory influence of endothelium on contractile
      responses to AII. Furthermore, in arteries with endothelium, it reduced the
      effect of both indomethacin and GR32191 B to the same level as observed in
      vessels without functional endothelium. 6. The results suggest that enhanced
      contraction caused by COX products was counteracted by enhanced relaxation caused
      by endothelium-derived NO in resistance mesenteric arteries of the SHR exposed to
      AII, compared to WKY arteries. The COX products involved in alterations of SHR
      responses comprised an endothelium-derived prostaglandin activating TP receptors
      and another nonendothelial unidentified vasoconstrictor compound which did not
      activate these receptors.

PMID- 8982513
TI  - Lack of beneficial effects on the NO-donor, molsidomine, in the L-NAME-induced
      pre-eclamptic syndrome in pregnant rats.
AB  - 1. In pregnant rats, chronic NO-synthase inhibition induces the development of a
      pre-eclamptic syndrome, characterized by an increase in maternal blood pressure,
      a loss of vascular refractoriness to pressor stimuli, a reduction in litter size
      and a decrease in pups (and maternal) weight. We investigated whether a NO-donor,
      molsidomine, administered during NO synthase inhibition, could restore a normal
      pregnancy. 2. Pregnant rats were given daily, starting from day 14 of gestation,
      saline (controls), or L-NAME (50 mg kg-1 d-1), or molsidomine (15 or 30 mg kg-1 d
      1), or the L-NAME + molsidomine combinations. Maternal blood pressure and body
      weight, litter size, pups weight and vascular reactivity to pressor stimuli
      (angiotensin II, noradrenaline, electrical stimulation of the spinal cord) were
      investigated. 3. L-NAME alone, as compared to controls, increased maternal blood
      pressure, reduced litter size (-59%), increased foetal reabsorptions (+ 625%) and
      decreased foetal weight (-10%). Vascular reactivity to pressor stimuli was
      enhanced. 4. Molsidomine alone, as compared to controls, dose-dependently
      decreased maternal blood pressure but had no effect vascular reactivity and,
      whatever the dose, on foetal outcome. 5. The L-NAME-molsidomine combinations dose
      (of molsidomine)-dependently limited the rise in maternal blood pressure induced
      by L-NAME alone but unexpectedly, dose-dependently and significantly worsened
      pregnancy evolution, e.g., at 30 mg kg-1 d-1: litter size (-80%), foetal
      reabsorptions (+ 1025%), foetal weight (-24%). Vascular reactivity to pressor
      stimuli was paradoxically further enhanced. 6. Thus, in a chronic NO deprivation
      induced model of pre-eclampsia in rats, molsidomine, possibly because of its
      hypotensive action, worsens the foetal outcome, which questions the usefulness of
      NO-donors in pre-eclamptic women.

PMID- 8982514
TI  - The inhibitory effects of alpha(2)-adrenoceptor agonists on gastrointestinal
      transit during croton oil-induced intestinal inflammation.
AB  - 1. The peripheral effects of alpha(2)-adrenoceptor agonists were investigated in
      a model of intestinal inflammation induced by intragastric administration of
      croton oil (CO). Our hypothesis was that inflammation would 'sensitize'
      adrenoceptors in peripheral and/or central terminals of myenteric and submucous
      plexus neurones, and enhance systemic effects of alpha(2)-adrenoceptor agonists.
      2. Male swiss CD-1 mice, received intragastrically CO (0.05 ml), castor oil (CA,
      0.1 ml) or saline (SS) 3 h before the study: gastrointestinal transit (GIT) was
      evaluated 20 min afterwards with a charcoal meal. The presence of inflammation
      was assessed by electron microscopy. 3. The intragastric administration of CA or
      CO caused an increase in GIT and weight loss, but only CO induced an inflammatory
      response. Both clonidine (imidazoline1/alpha(2)-agonist) and UK-14304 (alpha(2)
      agonist) produced dose-related inhibitions of GIT in all groups. During
      inflammatory diarrhoea (CO), potencies of systemic (s.c.) clonidine and UK-14304
      were significantly increased 3.5 and 2.1 times, respectively, while potencies
      remained unaltered in the presence of diarrhoea without inflammation (CA). The
      effects were reversed by administration (s.c.) of receptor-specific adrenoceptor
      antagonists, but not by naloxone. 4. Clonidine was 8.3 (SS) and 2.8 (CO) times
      more potent when administered intracerebroventricularly (i.c.v.), than when
      administered s.c. Inflammation of the gut did not alter the potency of i.c.v.
      clonidine, demonstrating that enhanced effects of s.c. clonidine are mediated by
      peripheral receptors. During inflammation, i.c.v. efaroxan did not antagonize low
      doses of s.c. clonidine (ED20 and ED50S), but partially reversed ED80S, further
      supporting the peripheral effects of the agonists in CO treated animals. 5. The
      results demonstrate that inflammation of the gut enhances the potency of alpha(2)
      adrenoceptor agonists by a peripheral mechanism. The results also suggest that
      the inflammatory response induces an up-regulation or sensitization of alpha(2)
      adrenoceptors and/or imidazoline receptors.

PMID- 8982516
TI  - The involvement of sensory neuropeptides in toluene diisocyanate-induced tracheal
      hyperreactivity in the mouse airways.
AB  - 1. Recently, we developed a murine model to investigate toluene diisocyanate
      (%DI)-induced occupational asthma. After skin-sensitization and intranasal
      challenge with TDI (1%) mice exhibited tracheal hyperreactivity 24 h after the
      challenge. 2. The aim of the present study was to investigate the possible role
      for sensory neuropeptides in the development of this tracheal hyperreactivity. 3.
      First, we demonstrated that direct application of TDI in vitro induced the
      release of tachykinins from the sensory nerves in the mouse isolated trachea.
      Second, capsaicin pretreatment, resulting in the depletion of sensory
      neuropeptides, completely abolished the TDI-induced tracheal hyperreactivity 24 h
      after the challenge. Third, the selective neurokinin1 (NK1)-receptor antagonist
      RP 67580 (0.2 mumol kg-1) also inhibited tracheal hyperreactivity when it was
      administered before the challenge. However, administration of RP 67580 during the
      sensitization phase did not result in a suppression of the TDI-induced tracheal
      hyperreactivity 24 after the challenge. 4. When TDI-sensitized mice were
      topically challenged with TDI a marked ear swelling response was observed. The
      cutaneous response after TDI application was not affected by capsaicin
      pretreatment or RP 67580 administration. 5. These results clearly show that
      sensory neuropeptides, particularly tachykinins, are essential for the
      development of TDI-induced tracheal hyperreactivity during the effector phase.
      The differences between the airways and skin with respect to the sensory
      neuropeptides is intriguing and could suggest a local action for the tachykinins
      in the airways.

PMID- 8982518
TI  - The potential and limits of competition in health care.

PMID- 8982515
TI  - Inhibition of cortical acetylcholine release and cognitive performance by
      histamine H3 receptor activation in rats.
AB  - 1. The effects of histamine and agents at histamine receptors on spontaneous and
      100 mM K(+)-evoked release of acetylcholine, measured by microdialysis from the
      cortex of freely moving, rats, and on cognitive tests are described. 2. Local
      administration of histamine (0.1-100 microM) failed to affect spontaneous but
      inhibited 100 mM K(+)-stimulated release of acetylcholine up to about 50%. The H3
      receptor agonists (R)-alpha-methylhistamine (RAMH) (0.1-10 microM), imetit (0.01
      10 microM) and immepip (0.01-10 microM) mimicked the effect of histamine. 3.
      Neither 2-thiazolylethylamine (TEA), an agonist showing some selectivity for H1
      receptors, nor the H2 receptor agonist, dimaprit, modified 100 mM K(+)-evoked
      release of acetylcholine. 4. The inhibitory effect of 100 microM histamine was
      completely prevented by the highly selective histamine H3 receptor antagonist,
      clobenpropit but was resistant to antagonism by triprolidine and cimetidine,
      antagonists at histamine H1 and H2 but not H3 receptors. 5. The H3 receptor
      induced inhibition of K(+)-evoked release of acetylcholine was fully sensitive to
      tetrodotoxin (TTX). 6. The effects of intraperitoneal (i.p.) injection of imetit
      (5 mg kg-1) and RAMH (5 mg kg-1) were tested on acetylcholine release and short
      term memory paradigms. Both drugs reduced 100 mM K(+)-evoked release of cortical
      acetylcholine, and impaired object recognition and a passive avoidance response.
      7. These observations provide the first evidence of a regulatory role of
      histamine H3 receptors on cortical acetylcholine release in vivo. Moreover, they
      suggest a role for histamine in learning and memory and may have implications for
      the treatment of degenerative disorders associated with impaired cholinergic
      function.

PMID- 8982519
TI  - Improving children's access to health care: the role of decategorization.
AB  - Far too many children in this country are unable to obtain the health care they
      need because of barriers that prohibit easy access. Among the most significant
      obstacles are financial barriers, including lack of adequate health insurance and
      inadequate funding of programs for low-income children and those with special
      health-care needs. Another set of "non-financial" barriers are related to the
      categorical nature of addressing children's health-care needs, which impedes
      access by increasing the complexity and burden of seeking care and discourages
      providers from providing care. Decategorization represents an appealing partial
      remedy to these problems because it can lead to fundamental and lasting changes
      in financing and delivering health services. The greatest appeal of
      decategorization is its potential to improve access to care with the expenditure
      of little or no new funds. Decategorization also holds considerable risk.
      Depending on how it is designed and implemented, decategorization may lead to
      diminished access to care by serving as a foil for budget cuts or by undermining
      essential standards of care. However, these risks do not negate the value of
      exploring decategorization as an approach that can be taken today to better
      organize services and ensure that existing resources adequately meet children's
      needs. In this report we examine the role of decategorization as a mechanism for
      removing the barriers to care that are created by categorical funding of health
      programs.

PMID- 8982520
TI  - School attendance, health-risk behaviors, and self-esteem in adolescents applying
      for working papers.
AB  - Since health-risk behaviors are often encountered in clusters among adolescents,
      it was hypothesized that adolescents with poor school attendance would be
      associated with more health-risk behaviors (e.g., substance use, violence) than
      those who attend school regularly. This study assessed the relationship between
      poor school attendance and health-risk behaviors, and described health-risk
      behaviors and self-esteem among adolescents seeking employment. In this cross
      sectional study, school attendance (poor vs. regular attendance) was related to
      health-risk behaviors by asking 122 subjects seen at a New York City Working
      Papers Clinic to complete both a 72-item questionnaire about their health-risk
      behaviors and the 58-item Coopersmith Self-Esteem School Form Inventory. Chi
      square and Fisher's Exact Tests were performed. The poor and regular attenders of
      school differed significantly in only 5 out of 44 items pertaining to health-risk
      behaviors. Self-esteem measures for the two groups did not differ from one
      another or from national norms. In this sample, depression "in general" (global)
      and "at home," but not "at school," were associated significantly with suicidal
      thoughts/attempts and serious past life events (e.g. family conflict, sexual
      abuse). There were no significant associations between depression or self-esteem
      and illicit substance or alcohol use. We found few associations between poor
      school attendance and health-risk behaviors in this sample of employment-seeking
      adolescents. The poor and regular attenders of school were similar in most
      aspects of their health-risk behaviors and self-esteem.

PMID- 8982521
TI  - Resilience in highly stressed urban children: concepts and findings.
AB  - The Rochester Child Resilience Project is a coordinated set of studies of the
      correlates and antecedents of outcomes relating to resilience among profoundly
      stressed urban children. The studies have been conducted over the course of the
      past decade. Based on child test data, parent, teacher, and self ratings of child
      adjustment, and in-depth individual interviews with parents and children, a
      cohesive picture has developed of child and family milieu variables that
      consistently differentiate children with resilient versus stress-affected
      outcomes within this highly stressed sample. Resilient children are characterized
      by an easy temperament and higher IQ; sound parent/child relationships; a
      parent's sense of efficacy; the parent's own wellness, especially mental health;
      and the child's perceived competence, realistic control, empathy, and social
      problem-solving.

PMID- 8982522
TI  - Similarity of risk and protective behaviors among African-American pre- and early
      adolescent members of naturally occurring friendship groups.
AB  - To determine whether self-reported risk and protective behaviors, expectations,
      and attitudes are more similar among African-American early adolescents within a
      community-based friendship group than across groups, a cross-sectional study was
      conducted among 382 African-American youth 9 through 15 years of age forming 76
      community-based groups of 3 through 10 same-gender friends. Each member of the
      friendship group reported his/her own past involvement in nine risk behaviors
      (sexual intercourse, substance abuse, drug-trafficking, and other delinquent
      activities) and two protective behaviors (high academic performance and regular
      church attendance) and their expectations and feelings regarding several of these
      behaviors. Intraclass correlation coefficients were calculated overall and by
      gender and age. Members were generally more similar within friendship groups than
      across groups with regard to several risk behaviors and expectations including
      sexual intercourse and drug-trafficking. Particularly striking was the similarity
      among members of "junior" friendship groups (e.g., median age of youth < 11
      years) of both risk and protective behaviors and expectations. The finding of
      enhanced similarity of risk behaviors and expectations among members within
      groups suggests that intervention delivery through community-based friendship
      groups may be a useful approach for risk prevention efforts targeting pre
      adolescent African-American youth living in low-income settings.

PMID- 8982523
TI  - One approach to care for patients infected with human immunodeficiency virus in
      an academic medical center.
AB  - The human immunodeficiency virus (HIV) epidemic poses unprecedented challenges to
      the health-care system. Caregivers must contend both with the complicated
      clinical syndromes associated with HIV infection and with issues that are central
      to the epidemic, such as discrimination, isolation, poverty, and substance abuse.
      Our HIV treatment program combines and enhances the resources of an academic
      medical center in a multidisciplinary care model. All patients, regardless of
      payor class, are offered services from 10 different disciplines. The same team of
      clinicians follows patients in the clinic and hospital. The program is flexible,
      non-hierarchical, and open to community participation. This approach may be a
      useful model for other institutions.

PMID- 8982524
TI  - Variability in patient experiences at 15 New York City hospitals.
AB  - To examine how patient experiences of the interpersonal aspects of quality of
      care varied among a group of 15 New York City hospitals, and the extent to which
      hospital and patient characteristics explained interhospital variability, a
      telephone survey was conducted with 3,423 randomly selected patients discharged
      from 15 New York City hospitals. Bivariate analysis, multiple linear regression,
      and least square means were used to assess the effects of 5 hospital
      characteristics and 15 patient characteristics on reports about problems with
      care. Outcome measures included patients' reported problems with selected aspects
      of care, patients' ratings of care, and patients' willingness to recommend the
      hospitals from which they had been discharged. The 15 hospitals varied widely in
      the rates at which patients reported problems with their care (10.7-21.7, mean =
      14.8, p < 0.001). A multivariate model showed that patients in fair or poor
      health, those without a regular doctor, younger patients, and minorities other
      than black and Hispanic were more likely to report problems with aspects of their
      care. Medicaid volume was also a strong, significant predictor of problem scores.
      Patient reports can be used to measure differences in quality of interpersonal
      care among hospitals. Only some of these differences are explained by patient and
      hospital characteristics, indicating that other factors facilitate or inhibit the
      delivery of high-quality interpersonal care.

PMID- 8982526
TI  - Re-engineering the public hospital system: saving the safety net.
AB  - Cities across America are grappling with the problem of how to provide care for
      the indigent and those on Medicaid. All levels of government are reducing their
      public funding for health care of indigent persons, and the rapid growth of
      managed care is making traditional cost-shifting more difficult as it transforms
      the practice of medicine itself. These issues are most acute in cities like Los
      Angeles and New York, which traditionally have relied on public hospital systems
      to serve as a safety net. This article focuses on the changes being wrought at
      the largest health-care system in the country for indigents, the New York City
      Health and Hospitals Corporation (HHC), on the progress it made during the first
      18 months of a major re-engineering process, and on potential options for its
      future reform.

PMID- 8982525
TI  - Adolescent alcohol use: social determinants and the case for early family
      centered prevention. Family-focused prevention of adolescent drinking.
AB  - The family plays a central role in the use of alcohol by children and
      adolescents, yet preventive interventions rarely focus on the family. Early
      drinking and much subsequent use of alcohol by children and adolescents is
      sanctioned and sometimes encouraged by their families. Unlike experimentation
      with alcohol, problem drinking is associated with low levels of family social
      support and with dysfunctional coping strategies of families that may lead
      children to use drinking as an adaptive behavior. While risk-factor research has
      advanced understanding of alcohol use by children and youth, the poor predictive
      power of individual risks has limited its contribution to successful
      interventions. On the other hand, protective factors, provided by relationships
      within and outside the family, can be preventive and health promoting. Parents
      influence their children's drinking through family interactions, modeling and
      reinforcing standards, and attitudes that children learn and use to guide their
      behavior in new situations. Thus, parental influences endure. This article argues
      that interventions to prevent alcohol abuse should be designed to help parents to
      carry out their parental functions. This can be accomplished by providing social
      support, resources, and education for parents, as well as developing extra
      familial sources of social support and socialization for children and
      adolescents.

PMID- 8982528
TI  - Efforts by the American Academy of Pediatrics to prevent and reduce violence and
      its effects on children and adolescents.
AB  - The American Academy of Pediatrics (AAP) is an organization of 53,000
      pediatricians committed to the attainment of optimal physical, mental, and social
      health for all infants, children, adolescents, and young adults. Recognizing the
      major impact that violence has on children and youth, the AAP has been working to
      prevent and reduce violence and its effects on the pediatric population. This
      article will describe AAP efforts intended to help pediatricians, other
      professionals, and the public to combat the problem.

PMID- 8982529
TI  - Breaking the mold: organizing medical care for New York City.

PMID- 8982527
TI  - Occupations, cigarette smoking, and lung cancer in the epidemiological follow-up
      to the NHANES I and the California Occupational Mortality Study.
AB  - What jobs are associated with the highest and lowest levels of cigarette use and
      of lung cancer? Are there gender differences in these jobs? Two data sets-the
      Epidemiological Follow-up to the National Health and Nutrition Examination Survey
      (NHEFS) and the California Occupational Mortality Study (COMS) were analyzed to
      answer these questions. For females, the broad occupations ranking from highest
      to lowest cigarette use in the NHEFS was: transportation operators, managers,
      craft workers, service workers, operatives, laborers, technicians, administrative
      workers, farm owners and workers, sales workers, no occupation, and
      professionals. The corresponding ranking for males was: transportation operators,
      no occupation, laborers, craft workers, service workers, technicians, and
      professionals. The highest-ranking jobs in the COMS were waitresses, telephone
      operators, and cosmetologists for women, and water-transportation workers,
      roofers, foresters and loggers for men. Teachers were especially low on all four
      lists. This study could not determine whether employment within any occupation
      encouraged smoking or if smokers selected certain occupations.

PMID- 8982530
TI  - The hospital as a human system. Reprinted from Physics in Medicine and Biology,
      Vol. 7, No. 2, pp. 147-155, October 1962.

PMID- 8982531
TI  - Hospitals and health services enterprises as social systems.

PMID- 8982532
TI  - 150 years of the New York Academy of Medicine: a series of exhibitions.
AB  - As the New York Academy of Medicine celebrates its 150th year as a leader in the
      field of urban health, it is instructive to review the events and decisions that
      influenced and shaped it. Since its inception, the Academy has taken an active
      role in lobbying state and local governments to enact more-effective public
      health laws and in educating the public about improving health conditions. During
      1996 and 1997, the Academy Library's Historical Collections is mounting a series
      of six exhibitions that are intended to tell the story of public health in New
      York as influenced by the New York Academy of Medicine. The story will be told
      using printed books, pamphlets, posters, photographs, and manuscripts drawn from
      the Library's collections, as well as the Academy's archives. Each exhibition
      will highlight the Academy's accomplishments in the subject areas presented. In
      this article, we summarize all six of the exhibitions and offer an in-depth look
      at the first two exhibitions.

PMID- 8982533
TI  - Malaria in New York City.

PMID- 8982534
TI  - Plasma cytokine levels in patients with severe burn injury--with reference to the
      relationship between infection and prognosis.
AB  - Blood levels of various cytokines were determined in patients with burn injury
      immediately after the accident, and the relationship between cytokines and morbid
      condition was investigated. There was almost no marked elevation of cytokines in
      the early stage of burn injury. Throughout the entire course, tumour necrosis
      factor alpha, interleukin 6 and interleukin 8, as cytokines, showed high levels
      in patients with burn injury associated with sepsis and those who died. These
      levels well reflected the severity in the phase complicated with sepsis.

PMID- 8982535
TI  - Plasma levels of endothelin-1 and thrombomodulin in burn patients.
AB  - Plasma concentrations of endothelin-1 (ET-1) and thrombomodulin (TM) were
      determined in patients with burns to examine their relation to the severity of
      illness. Tumor necrosis factor-alpha (TNF-alpha) was also measured, and its
      relationship to ET-1 and TM determined. Twenty-three burn patients were
      evaluated, who had a total burn surface area (TBSA) of at least 20 per cent. ET-1
      was measured by radioimmunoassay (RIA). TM and TNF-alpha were measured by enzyme
      linked immunosorbent assay (ELISA). Both the ET-1 and TM concentrations were
      significantly higher in the patients who developed sepsis than in those who did
      not and in the patients who eventually died than in those who survived. Maximum
      plasma concentrations of ET-1 and TM were significantly correlated with the acute
      physiological and chronic health evaluation II score. There was also a
      significant correlation between the plasma levels of TNF-alpha and both ET-1 and
      TM. ET-1 and TM closely reflect the severity of illness in patients with burns in
      the infectious stage; TNF-alpha may be involved in the production of ET-1 and TM.

PMID- 8982536
TI  - Colonic pseudo-obstruction in burns patients.
AB  - Acute pseudo-obstruction is a rare complication in burns patients. An awareness
      of the factors implicated in its pathogenesis such as prolonged bed rest,
      narcotic medications, hypokalaemia, sepsis and surgery (all commonly associated
      with burns patients) is essential if this condition is to be avoided. Early
      diagnosis, prokinetic and cathartic agents, and aggressive endoscopic
      intervention are essential to halt the progression of caecal dilatation.
      Excisional surgery and stoma formation are necessary for salvage of complicated
      colonic pseudo-obstruction.

PMID- 8982537
TI  - Alteration in sensory nerve function following electrical shock.
AB  - A study of the effects of electrical shock on peripheral nerve fibres is
      presented. Strength and duration of the applied shocks were similar to those
      encountered in a typical industrial electrical accident. The purpose of this
      study is: (i) to identify the electrophysiological and morphological change in
      nerve fibres after the application of electrical current shocks; (ii) to examine
      the ability of the peripheral nerve fibres to spontaneously regain function and;
      (iii) to demonstrate the usefulness of the sensory refractory spectrum as an
      additional technique in assessing the damage. Three groups of animals received
      twelve 4-ms electric field pulses of approximately 37 V/cm (n = 5), 75 V/cm (n =
      9) and 150 V/cm (n = 6), respectively. Group 4 was a control group and received a
      direct application of 2 per cent lidocaine over the sciatic nerve for 30 min.
      Thermal effects of the shocks were negligible. The sensory refractory spectrum
      shows that electrical shock damage was mainly to the large, fast myelinated
      fibres and that higher field strengths do more damage. Also in a histological
      examination it was found that the more heavily shocked myelinated fibres had
      sustained more damage.

PMID- 8982538
TI  - Calculation of a new Meeh constant and experimental determination of burn size.
AB  - With advances in research techniques involving molecular biology, the need for
      precision in the determination of surface area is even greater than previously.
      This study sets out to determine the most accurate Meeh constant, k, for a
      commonly used weight range of experimental rats. The importance of a narrow
      weight range is appreciated and planometric data is presented from a series of
      adolescent rats that allow a new k value to be calculated. The figures presented
      here represent the largest number of animals, of a commonly used rat strain, in
      the most widely used weight range yet described. Pelts were removed from 16
      anaesthetized male Sprague-Dawley rats after cervical dislocation. For each
      animal total body surface area (TBSA) was determined planometrically, along with
      premarked areas on the dorsal and ventral surfaces. Entering the planometrically
      measured data along with the animal's weight into the Meeh formula, a k value was
      obtained for each rat. Surface areas were then calculated for each animal using
      the mean k, 9.46, and compared against figures obtained by using historical
      values for the Meeh constant. Using the new k value a method is described for the
      accurate determination of total body surface area and premarked surface areas, in
      experimental rats of a specific weight range.

PMID- 8982540
TI  - Emotional and psychosocial factors in burn patients during hospitalization.
AB  - This is a preliminary study of psychological symptoms, prior psychosocial
      adjustment and severity of injury in 25 consecutive burn patients. All had
      suffered burns in work-related accidents and were evaluated by the psychiatric
      consulation-liaison team during their initial hospitalization in the Burn Unit of
      the Hospital del Trabajador, Santiago. All patients were clinically evaluated and
      the following instruments were applied: Hamilton Scales of Anxiety (HAM-A) and
      Depression (HAM-D), Goldberg's General Health Questionnaire (GHQ-28), Cloninger's
      Tridimensional Personality Questionnaire (TPQ) and a modified version of a
      Schooler's Adjustment Scale. No significant correlation was found between extent
      and severity of burns and anxious or depressive symptoms. However, all patients
      had burns that varied from mild to moderate; there were no severe and extensive
      injuries. A significant correlation was found between anxiety and the harm
      avoidance dimension in the TPQ, as would be expected. Patients with poor
      psychosocial adjustment presented with greater anxiety symptoms. A significant
      negative correlation was also found between degree of anxiety symptoms and income
      level. The main findings are in agreement with current literature. They emphasize
      the relevance of prior psychosocial adjustment and personality as probable
      factors of psychological symptoms. The need to control pain as a variable is also
      pointed out.

PMID- 8982539
TI  - In vitro induction of anti-type 2 T cells by glycyrrhizin.
AB  - Glycyrrhizin (GR), an active component of licorice roots, has been previously
      shown to induce the generation of anti-type 2 T cells (anti-BI2T cells), which
      are able to counteract the activity of burn-induced CD8+ type 2 T cells (BI2T
      cells), in thermally injured and normal mice. In the present study, anti-BI2T
      cells were generated in vitro in cultures of spleen cells stimulated with GR.
      Anti-BI2T cells were induced in vitro when splenic mononuclear cells (SMNC) were
      stimulated in vitro for 24 to 72 h with 0.1-10 micrograms/ml of GR. Anti-BI2T
      cell activity was detected when suppressor macrophages (M phi) were depleted from
      SMNC after stimulation with GR. However, the GR-stimulated generation of anti
      BI2T cells required the participation of M phi or their sonicated fractions. Anti
      BI2T cells induced in vitro by GR were identified as Vicia villosa lectin
      adherent IFN7 producing-CD4+ T cells lacking the ability to produce IL-2, IL-4 or
      IL-10. These results indicate that anti-BI2T cells are generated by GR in vitro.
      M phi are not only necessary for the generation of anti-BI2T cells induced by GR
      but also inhibit their activity.

PMID- 8982541
TI  - Outcome studies for burn patients in Hong Kong: patients' satisfaction.
AB  - With the recent advances in burns treatment, many more survive the burn to
      experience pain, scarring, physical deformity, loss of function and psychological
      trauma. Pressure therapy prescribed by occupational therapists for more than 20
      years in Hong Kong has proved its effectiveness in treating the visible scars.
      However, the inconvenience and impaired appearance that is brought about by these
      garments during the long phase of therapy bears some weight in worsening
      patients' social acceptance and happiness in life, also their families especially
      in children. The objects of the studies were to measure the subjective rating of
      the effectiveness of pressure therapy through patients' satisfaction towards
      treatment effectiveness and its effect on daily life. Seventy cases with burn
      injuries over 1 year previously were selected randomly among the centres for the
      survey. The scale used was ordinal from 1 to 6. Eleven items concerning treatment
      effectiveness, life at home, work and leisure aspects were questioned. Results
      were analysed into two streams-satisfaction towards pressure therapy and change
      of life satisfaction pre- and post-injury. Non-parametric tests were used for
      data analysis. Through the Wilcoxon Sign Rank Test and Cluster analysis, major
      determinants were identified. These factors also showed significant correlation
      with this demographic data. The conclusions helped to evaluate and improve the
      existing service in both the garment properties and our scope of therapy for
      these patients, especially in work rehabilitation and finally (sexual)
      counselling which should be addressed by a team with interdepartmental support.

PMID- 8982542
TI  - Management of hypopigmentation following burn injury.
AB  - Hypopigmentation is a troublesome often permanent sequelae following burn injury,
      particularly in dark races. A number of methods have been described to treat this
      phenomenon ranging from primary closure, split skin and particulate grafting as
      well as semipermanent and permanent camouflage. This article reviews the
      pathophysiology of this condition and discusses the indications for using each
      technique as well as the potential for future developments in melanocyte culture.

PMID- 8982543
TI  - Effect of facial burns on the nasal mucosa.
AB  - In this study the nasal mucosa of patients who had recently sustained facial
      burns was examined endoscopically. The saccharin clearance test was performed as
      a measure of nasal mucociliary transport. All the patients had singed nasal
      hairs, but none had inflammatory changes extending beyond the nasal valve. In
      only one patient was the saccharin clearance prolonged beyond 20 min, and only
      one patient developed nasal obstruction postburn. This study shows that the nasal
      mucosa is resistant to damage when the face is burned, suggesting the nose is an
      efficient heat exchanger, and the nasal mucosa should preserve its capacity to
      absorb drugs.

PMID- 8982544
TI  - Psoralens used for cosmetic sun tanning: an unusual cause of extensive burn
      injury.
AB  - Psoralen combined with long-wave ultraviolt radiation (UV-A) has become a
      standard method of psoriasis treatment. A well-known and often appreciated 'side
      effect' is the hyperpigmentation caused by this treatment. Three patients
      demonstrating a novel cause of severe skin loss, 'psoralen burn', are presented.
      No patient was afflicted by psoriasis and all three had used psoralen and
      ultraviolet exposure with the intent to enhance sun tanning. In the case
      histories presented, it is notable that two of the patients share an alarmingly
      extensive skin injury (90-95 per cent body surface area), while the third had an
      extensive but rather superficial injury. In addition, a very similar time-table
      for the development of the injury could be observed, with a maximum distribution
      of skin loss not reached until 7 or 8 days after exposure. Psorelen-UV-A can
      cause life-threatening skin losses when used in an erratic manner. Early
      recognition of the nature and knowledge of the time-course in the development of
      these lesions is necessary for optimal treatment. Some principles of treatment
      are discussed. Dermatologists prescribing PUVA treatment should further increase
      their warnings of uncontrolled use of psoralens in non-psoriatrics.

PMID- 8982545
TI  - Burns related to the use of psoralens as a tanning agent.

PMID- 8982546
TI  - Electrical injuries from graphite fishing rods.
AB  - High tension electrical injuries have a high morbidity and mortality. Carbon
      fibre and graphite used in the manufacture of fishing rods gives them
      superconductor qualities. The resistance of a fishing rod with a carbon content
      of more than 70 per cent is very low, ranging from 0.9 to 10.5 k omega. Nine
      cases are reported, which teach an important lesson not only in the management of
      those severe injuries, but also in their prevention.

PMID- 8982547
TI  - Distally based dorsalis pedis island flap for a distal lateral electric burn of
      the big toe.
AB  - Reconstruction of the small defects in the distal portion of the foot has always
      represented a difficult problem. A case of a young man with a deep electric burn
      of the distal lateral side of the big toe successfully treated with a distally
      based dorsalis pedis island flap based on the first dorsal metatarsal artery
      (FDMA) is presented. The donor site area of the dorsum of the foot was grafted,
      and deambulation was reassumed 3 weeks later. Advantages; limits and anatomical
      consideration regarding the viability of the flap are also discussed.

PMID- 8982549
TI  - Cement-related burns.
AB  - Burns caused by prolonged contact of wet cement with skin are common in this
      country. Recent literature has highlighted other ways in which the use and
      manufacture of cement can lead to burn injuries, notably through explosion and
      contact with hot powder during manufacturing. These injuries are uncommon in this
      country and potentially very serious. Case studies are presented of two men
      injured in such a way in the same incident at a cement-manufacturing plant.

PMID- 8982548
TI  - Full-thickness foot burn of a pilgrim to Mecca.
AB  - This report relates to burns of the feet suffered by a pilgrim to Mecca who
      walked barefoot in the hot desert sun. He subsequently presented with full
      thickness burn injuries to the soles of his feet. When the patient developed
      acute coronary insufficiency, immediate surgery could not be performed. He was
      therefore treated conservatively with salicylic acid and Silverol cream.
      Spontaneous closure of the wounds was achieved in the course of 2 months.

PMID- 8982550
TI  - Proteinuria as a consequence of altered glomerular permselectivity--clinical
      implications.

PMID- 8982551
TI  - Clinical and morphological predictors of renal outcome in adult patients with
      focal and segmental glomerulosclerosis (FSGS).
AB  - In this retrospective study, we examined 35 adult patients with biopsy-proven,
      primary focal and segmental glomerulosclerosis (FSGS) and nephrotic syndrome to
      determine whether any of the clinical and morphological features of FSGS were
      associated with a higher risk of a poor renal outcome. Clinical factors assessed
      were the age, sex, amount of urinary protein, and presence of microscopic
      hematuria, hypertension and renal dysfunction at onset in each patient.
      Morphological parameters included the number of segmental sclerosis and global
      sclerosis, sclerosis score, location of segmental sclerosis, mean glomerular
      diameter, grade of tubulo-interstitial changes, and presence of vascular lesions.
      Twenty-three patients (66%) were in complete or incomplete (partial) remission,
      and 12 (34%) were non-responders at the end of follow-up. On univariate analysis,
      the age at onset, sclerosis score, mean glomerular diameter, and grade of tubulo
      interstitial changes in no response were significantly greater than those
      parameters in remission. Multivariate logistic regression analysis revealed that
      the degree of tubulo-interstitial changes and mean glomerular diameter were
      independent risk factors for a poor renal outcome. These findings suggest that
      the estimation of these latter two parameters allows the nephrologist to predict
      the probable course and prognosis of an adult with FSGS. Intensive and prolonged
      therapy is recommended for patients without these two morphological features.

PMID- 8982552
TI  - Pulmonary involvement in nephropathia epidemica: radiological findings and their
      clinical correlations.
AB  - Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome (HFRS)
      normally taking a benign clinical course. The etiologic agent, Puumala hantavirus
      is genetically closely related to Sin Nombre virus, which causes a frequently
      lethal febrile syndrome with pulmonary involvement (hantavirus pulmonary
      syndrome, HPS). HPS is characterized by acute respiratory distress, non
      cardiogenic pulmonary edema and severe and hypotension, but usually no
      significant renal involvement. Pulmonary involvement and respiratory symptoms
      also occur in NE. To understand the mechanisms of pulmonary involvement in NE, we
      studied the clinical records and chest X-rays of 125 hospital-treated acutely ill
      NE patients. Twenty-eight percent of the patients had disease-related changes in
      their chest radiographs. Pleural effusion and atelectasis were the most common X
      ray findings, whereas frank pulmonary edema was rare. The patients with
      pathologic X-ray findings had a more marked hypoproteinemia (lowest measured
      serum protein concentration 54 +/- 1 g/l) than those with normal X-ray (62.1 +/-
      0.9 g/l, p < 0.001) and leukocytosis (highest measured blood leukocyte count 14.1
      +/- 0.9 x 10(9)/l vs. 10.6 +/- 0.6 x 10(9)/l, p < 0.001) and more severe renal
      insufficiency (highest measured serum creatinine 590 +/- 60 mumol/l vs. 356 +/-
      29 mumol/l, p < 0.05). Hypoproteinemia best predicted the occurrence of abnormal
      chest X-ray findings in NE. This suggests, that capillary leakage and
      inflammation may play a role in the pathogenesis of NE lung involvement,
      similarly as in HPS. Differently from HPS, the fluid volume overload associated
      with renal insufficiency seemed to contribute strongly to the chest X-ray changes
      in NE.

PMID- 8982553
TI  - Hantavirus antigen detection in kidney biopsies from patients with nephropathia
      epidemica.
AB  - Renal biopsies collected from ten patients with serologically confirmed
      Puumalavirus (PUUV) infection in the acute stage with renal dysfunction who lived
      in the same PUUV endemic area in The Netherlands, were studied histologically,
      immuno-histochemically and subsequently examined for the presence of viral
      antigen by immunoperoxidase staining. Interstitial hemorrhages and deposition of
      IgM, complement component C3 and fibrin along the basal side of the tubular
      epithelial cells, were found in PUUV seropositive patients. In six of these
      patients viral antigen was detected in the cytoplasm of renal tubular epithelial
      cells with focal distribution in the cortical and medullary areas of the kidneys.
      Surprisingly, also in two of the ten renal biopsies from PUUV seronegative
      patients, PUUV antigen was demonstrated, with essentially the same localization.
      Comparison of severity and extent of the lesions in the seropositive group with
      those of these two patients showed no significant differences between tubular and
      interstitial abnormalities. These findings indicate that the demonstration of
      certain histopathological alterations and the detection of viral antigen by
      immunoperoxidase techniques in kidney biopsies, may be useful as additional tools
      for the diagnosis of PUUV infection.

PMID- 8982555
TI  - The effect of oral 1 alpha-hydroxycalciferol treatment on bone mineral density in
      hemodialysis patients.
AB  - We have studied the effect of different doses of 1 alpha-hydroxycalciferol (1
      alpha [OH]D3) on bone mineral density (BMD) of 165 male hemodialysis patients
      (ages from 24 to 71 years) using dual X-ray absorptiometry (DXA) in a one-year
      follow-up study. There were no fractures in their lumbar spine participated in
      the study. 1 alpha (OH)D3 was administered orally at a low dose (0.25
      microgram/day, n = 56, Group L) or at a higher dose (0.5 to 1.0 microgram/day,
      average 0.58 +/- 0.02 microgram/day, n = 65, Group H), and the absolute BMD
      values and the percent annual changes of BMD were compared with those who took no
      1 alpha (OH)D3 (n = 44, Group N). BMD was measured three ways at the start and
      the end of the study; 1) lumbar spine BMD at anterior-posterior view (AP-BMD), 2)
      lumbar spine BMD at lateral view (Lat-BMD), and 3) 1/3 distal radius BMD. Plain
      spinal radiographs indicated no bone fracture before nor during the study.
      Although there were no detectable changes in the absolute values of BMD during
      the one-year period, significant differences were observed in the percent annual
      changes of lumbar spine BMD among the three groups. The annual changes of lumbar
      spine BMD among the three groups. The annual changes of AP-BMD were -0.4 +/-
      0.7%, +0.1 +/- 0.6%, and +2.4 +/- 0.8% in Group N, Group L and Group H,
      respectively. These changes were statistically significant (p = 0.011 by one-way
      ANOVA). The positive effect of 1 alpha (OH)D3 on Lat-BMD was also significant (p
      = 0.028 by one-way ANOVA), while the treatment did not affect the change of BMD
      at 1/3 distal radius. There was no significant difference among the three groups
      in the initial or final levels of biochemical parameters including serum calcium,
      phosphorus, alkaline phosphatase, osteocalcin and parathyroid hormone. These
      results indicate, in male hemodialysis patients, that oral 1 alpha (OH)D3
      treatment is effective in the prevention of lumbar spine BMD loss which is
      frequently observed in hemodialysis patients.

PMID- 8982554
TI  - Renal length in sickle cell disease: observations from a cohort study.
AB  - Renal length has been measured by ultrasound in 237 subjects with homozygous
      sickle cell (SS) disease, 147 with sickle cell-hemoglobin C (SC) disease, and in
      78 age-matched controls with a normal hemoglobin (AA) genotype. As expected,
      renal length increased with age in all genotypes but mean length was
      significantly greater in SS disease compared with SC disease (mean difference 4.3
      mm after adjustment for height) and significantly greater in both genotypes than
      in AA controls (SS/AA difference 9.2 mm, SC/AA difference 5.0 mm after adjustment
      for height). Examination of relationships between renal length and some
      hematological indices (hemoglobin, fetal hemoglobin, reticulocyte counts, alpha
      thalassemia status) in SS or SC disease showed only a significant negative
      correlation with hemoglobin and positive correlation with reticulocyte count in
      SS disease. Further analysis suggested that the stronger relationship was between
      renal length and high reticulocyte count. The mechanism of renal enlargement is
      unknown although glomerular hypertrophy and increased renal blood volume are
      likely contributors.

PMID- 8982556
TI  - Transfer of cytokine-inducing bacterial products across hemodialyzer membranes in
      the presence of plasma or whole blood.
AB  - Cytokine production by peripheral blood mononuclear cells (PBMC) is a sensitive
      indicator of cytokine-inducing substances which may cross from contaminated
      dialysate into the blood compartment. The objective of this study was to compare
      the transfer of cytokine-inducing substances from dialysate contaminated with a
      culture filtrate from Pseudomonas aeruginosa across dialyzers with low (hemophan)
      or intermediate ultrafiltration coefficients (modified cellulose triacetate,
      CTA), under conditions where either 10% plasma or whole blood was circulated in
      the blood compartment. Eight paired experiments of in vitro dialysis were carried
      out at 37 degrees C using a countercurrent recirculating loop dialysis circuit
      with either a new CTA or hemophan dialyzer. 10% plasma in standard tissue culture
      medium was circulated through the blood compartment and bicarbonate dialysate was
      circulated in the dialysate compartment. The dialysate was challenged
      sequentially by log-fold dilutions (10(2), 10(3) or 10(4)) of a Ps. aeruginosa
      culture filtrate. Samples were drawn from the blood compartment 5 and 15 minutes
      after each challenge and incubated with suspensions of PBMC in the absence or
      presence of polymyxin B, in order to block endotoxin. After 24 h at 37 degrees C,
      total interleukin-1 alpha (IL-1 alpha) was measured by RIA. Although the
      dialysate contained potent cytokine-inducing substances, there was no significant
      IL-1 alpha production by PBMC incubated with the plasma mixture from the blood
      compartment in the majority of experiments with both dialyzers and with each of
      the three dilutions of the bacterial challenge. Eight experiments were also
      performed with CTA dialzyers using heparinized whole blood in the blood
      compartment. Samples of whole blood and dialysate were drawn at baseline, after
      one hour of dialysis with uncontaminated dialysate and 15 minutes and three hours
      after dialysis with dialysate contaminated with Ps. aeruginosa filtrate. There
      was no significant IL-1 alpha production by PBMC isolated from the whole blood 1
      h after dialysis with uncontaminated dialysate, and 15 min and 2 h after adding
      the Ps. aeruginosa filtrate to the dialysate side. In contrast, production of IL
      1 alpha by PBMC from the same donors incubated with samples from the dialysate
      were 263 +/- 50, 1074 +/- 306, 2333 +/- 774 and 2602 +/- 702 pg/2.5 x 10(6) PBMC,
      respectively at the same four time points. These data suggest that although the
      Ps. aeruginosa culture filtrate present in the dialysate was a potent inducer of
      IL-1 alpha, neither dialyzer permitted transfer of cytokine inducing substances
      from the dialysate into the blood compartment.

PMID- 8982557
TI  - Biocompatible dialysis membranes and acute renal failure: a study in post
      operative acute tubular necrosis in cadaveric renal transplant recipients.
AB  - Previous experimental and human data suggests a detrimental effect on the course
      of acute renal failure related to exposure of blood to artificial dialysis
      membranes of poor biocompatibility. We performed a 2.5-year prospective
      randomized trial to compare the clinical course of acute renal failure (post
      operative ischemic acute tubular necrosis, ATN) in patients receiving a cadaveric
      renal transplant requiring supportive hemodialysis in the immediate post
      transplant setting. Patients were randomized to either a cuprophane or
      polymethylmethacrylate (PMMA) conventional hollow fiber dialyzer. All patients
      received a standard immunosuppressive regimen which included induction therapy
      with either horse anti-thymocyte gamma globulin (ATGAM) or the murine anti-CD3
      monoclonal antibody (OKT3). Of 53 patients randomized, 17 were excluded (2 for
      intervening biopsy-proven rejection prior to recovery from ATN, 10 for primary
      graft nonfunction and 5 for other reasons), leaving 36 evaluable cases of
      uncomplicated ATN, 18 in each group. There was no difference by age, race,
      gender, cause of ESRD, immunosuppressive regimen, cold or warm ischemia time, use
      of pre-transplant dialysis, percent oliguria or the incidence of intra-dialytic
      hypotension between the 2 groups. There was no difference in the mean time to
      recovery from ATN posttransplant (8.9 days in the cuprophane group vs 9.5 days in
      the PMMA group, p = NS) or in the average number of hemodialysis treatments
      required (3.6 in both groups, p = NS). There was also no difference in long term
      allograft outcome in terms of the nadir serum creatinine, the number of episodes
      of subsequent acute rejection or in the development of chronic rejection. An
      intent-to-treat analysis of all 53 originally randomized patients similarly
      yielded no significant differences. A subsequent, non-randomized study using a
      membrane of intermediate biocompatibility (Hemophan) also showed no difference in
      recovery time from ATN. Bioincompatible membranes do not seem to have a
      significant clinical impact on the course of recovery of this form of acute renal
      failure. The striking benefits of biocompatibility in the course of ARF seen in
      other human trials may relate more to the non-renal systemic toxic effects of
      bioincompatibility.

PMID- 8982559
TI  - Alterations of HDL subfractions in patients with Balkan endemic nephropathy and
      in healthy family members.

PMID- 8982558
TI  - Erythropoiesis following renal transplantation; a reply to Jeffrey et al.

PMID- 8982560
TI  - Garland pattern post-streptococcal glomerulonephritis (PSGN, clinical
      characteristics and follow-up.

PMID- 8982561
TI  - Congenital diaphragmatic hernia. A historical review.
AB  - Congenital diaphragmatic hernia (CDH) has been described, studied, and treated
      for over 400 years. A historical perspective is given. Great strides have been
      made in the care of patients with CDH; however, the mortality rate remains 30% to
      60%. Consideration of historical references, observations, and achievements in
      the study of CDH is important for the continued advancement and improvement in
      our understanding of and future success in treating infants and children with
      CDH.

PMID- 8982562
TI  - Toward understanding the developmental anatomy of congenital diaphragmatic
      hernia.
AB  - The pathway of abnormal embryonic development leading to congenital diaphragmatic
      hernia (CDH) is incompletely understood. Using a nitrofen-induced model of left
      CDH in rats, sequential stages of development were analyzed by scanning electron
      microscopy. Abnormal development patterns were observed in the cells comprising
      the posthepatic mesenchymal plate and the adjacent liver. The septum transversum
      did not appear to be involved. In this article, the authors theorize that a
      disturbed "balance of cell growth" is responsible for the creation of the
      diaphragmatic defect.

PMID- 8982563
TI  - Congenital diaphragmatic hernia. Epidemiology and outcome.
AB  - Congenital diaphragmatic hernia is a relatively common birth defect. It affects
      about 1114 babies a year in the United States. Reported survival averages 60% but
      may be significantly lower. We do not understand the etiology of CDH. Its
      association with other anomalies and several distinct patterns of presentation
      suggest that more than one cause may exist. There is a high degree of variability
      in both treatment and outcomes, but no data exist to allow a rigorous comparison
      of the efficacy of various treatment strategies. Stratification of patients into
      more homogeneous groups will be a necessary prerequisite for the design of
      meaningful comparative trials. The incidence of the lesion prevents any single
      institution from accruing sufficient patients to conduct such a trial. An ad hoc
      multicenter study group (the Congenital Diaphragmatic Hernia Study Group) has
      been formed for this purpose. This organization has begun collecting data with an
      initial goal of developing a stratification scheme. Prospective data collection
      should allow verification of several of the estimates made in this article.
      Current data make it clear that CDH represents a major cause of perinatal
      morbidity and mortality.

PMID- 8982564
TI  - Etiologic and genetic factors in congenital diaphragmatic hernia.
AB  - The cause of CDH remains largely unknown. Although teratogenic factors have been
      described, no single gene mutation can be held responsible for this major
      congenital anomaly. The genetic background of familiar occurrence is variable.
      Careful documentation of both isolated and familiar cases, and the application of
      new techniques such as fluorescent in situ hybridization (FISH) and differential
      display in selected cases, might result in new explanations for possible genetic
      inheritance. Clinical evaluation of associated anomalies, together with
      increasing awareness of the genes involved in lung development, especially those
      guiding mesenchymal growth, will have great impact on increasing knowledge of the
      cause of this devastating anomaly.

PMID- 8982565
TI  - Prenatal diagnosis of congenital diaphragmatic hernia with predictors of
      mortality.
AB  - Since the late 1970s, congenital diaphragmatic hernia (CDH) has been diagnosed
      antenatally by ultrasound. With improvements in ultrasound resolution, CDH is
      being diagnosed more frequently and at an earlier stage in gestation. This
      provides an opportunity to administer in utero therapy to the fetus. As 50% of
      babies born with CDH survive, it is imperative that accurate prognostic
      indicators are available to guide antenatal therapy. Antenatal diagnosis and
      prognostic indicators are discussed.

PMID- 8982566
TI  - The normal pulmonary vascular transition at birth.
AB  - Although the normal pulmonary vascular transition at birth takes place quickly in
      the delivery room, it has its basis in the complex structural and biochemical
      development of the lung. We are only beginning to understand the stimuli that
      initiate and mediate the transition, as well as their interrelationships.
      Comprehension of normal structure and function is the foundation that will enable
      us to understand how this process is impaired in the baby born with congenital
      diaphragmatic hernia.

PMID- 8982567
TI  - The effects of mechanical forces on fetal lung growth.
AB  - Abnormalities of fetal lung growth, especially pulmonary hypoplasia, are
      important causes of neonatal morbidity and mortality. For most clinical
      conditions associated with abnormal lung growth, studies in experimental animals
      indicate that these conditions affect the mechanical forces acting on the fetal
      lung. The major stimulus to growth in the fetal lung is stretch, which is due
      either to (1) to the constant distending pressure during periods when fetal
      breathing movements are absent, or (2) the intermittent, repetitive stretch
      induced by changes in thoracic shape during fetal breathing movements. The
      mechanisms by which stretch is transduced to a biochemical signal stimulating
      cell division have not been defined. There are some indications that the
      mechanical forces that influence lung growth may also affect surfactant, but
      further studies are needed to define these effects and their possible clinical
      significance.

PMID- 8982568
TI  - The effect of mechanical forces on in utero lung growth in congenital
      diaphragmatic hernia.
AB  - Lung development is a complex process of lung growth and maturation. Although
      lung maturation appears to be principally regulated by hormonal and biochemical
      factors, lung growth appears to depend more on physical factors such as lung
      liquid volume, fetal breathing movements, the size of the intrathoracic space,
      and the amniotic fluid volume. This article focuses on these physical factors.
      Specific emphasis is given to the normal mechanisms responsible for lung growth,
      as well as the consequences of disruption of these normal mechanisms.

PMID- 8982569
TI  - Use of transgenic mice to study autocrine-paracrine signaling in lung
      morphogenesis and differentiation.
AB  - Transgenic mice have been useful in demonstrating critical autocrine-paracrine
      interactions that are mediated by polypeptide hormones and associated receptors.
      These systems control interactions between the pulmonary mesenchyme and
      epithelium that have profound influences on lung morphogenesis, cell
      proliferation, and differentiation and include both inhibitory and stimulatory
      pathways. These pathways underlie the process of branching, sacculation, and
      alveolar development and may be served by several redundant polypeptides and
      receptors that work in concert to ensure normal pulmonary development. It is also
      likely that the same systems are involved in the proliferation and
      differentiation that accompany repair following injury. It is hoped that these
      transgenic models will provide insight into growth factors and receptors involved
      in cell proliferation, differentiation, and function during pulmonary
      organogenesis and also will serve to clarify the role of growth factors that may
      influence repair following lung injury, as seen in bronchopulmonary dysplasia and
      pulmonary fibrosis following severe lung injury in clinical settings.

PMID- 8982570
TI  - Pulmonary parenchymal abnormalities in congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia results in abnormal lung development. There is a
      global hypoplasia with both lungs affected, the ipsilateral lung more severely.
      This results in a reduction in the number of bronchial divisions and a decrease
      in the quantity and maturity of the alveoli. The pneumocytes are dysfunctional,
      resulting in a total quantitative and qualitative reduction in surfactant and a
      decrease in antioxidant enzyme activity.

PMID- 8982571
TI  - Pulmonary vascular abnormalities in congenital diaphragmatic hernia.
AB  - Persistent pulmonary hypertension poses a significant problem to the surgeon
      managing an infant with congenital diaphragmatic hernia. It is likely that a
      number of abnormalities contribute to this pathophysiologic entity. These
      include: (1) in the hypoplastic lung the overall cross-sectional area of the
      pulmonary vascular bed is reduced, (2) the muscular arteries are hypertrophied
      and extend more peripherally than normal, (3) the pulmonary vessels are more
      labile than normal and are overly sensitive to the normal stimuli of
      vasoconstriction, and (4) the immature surfactant-deficient lung is predisposed
      to barotrauma and atelectasis, resulting in alveolar hypoxemia which contributes
      to pulmonary hypertension. All of these interfere with the ability of the lung to
      accept the increase in pulmonary blood flow required by the transitional
      circulation. If this impairment reaches a level such that the lung cannot accept
      the right ventricular output then pulmonary hypertension will ensue and a poor
      outcome can be anticipated.

PMID- 8982572
TI  - The fetal heart in diaphragmatic hernia.
AB  - Cardiac evaluation is an important part of the investigation of a fetus with a
      diaphragmatic hernia. The heart is displaced by the physical presence of the
      abdominal contents in the chest, and the flow dynamics within the heart are
      altered. This can produce secondary diminution of chamber growth, particularly of
      the left heart. Structural heart malformation is also a frequently associated
      finding. Evaluation of cardiovascular flow profiles may give us further
      understanding of the pathophysiology of this lesion and may help to predict those
      fetuses that might benefit from intrauterine therapy.

PMID- 8982573
TI  - Animal models in congenital diaphragmatic hernia.
AB  - The first animal model of congenital diaphragmatic hernia (CDH) was described in
      1967. This was a late-gestational, surgically-created lamb model. Since then,
      animal modeling has become more sophisticated. Using a variety of techniques and
      laboratory species, animal models have been produced to investigate the
      pathophysiology of CDH, from whole animal physiology studies to lung molecular
      changes. To provide the animal tissue required, three different approaches have
      been used: (1) a surgically-created model which has been reported in lambs and
      rabbits, (2) a teratogen-induced model which to date has been described in rats
      and mice, and (3) a congenital model which is present in a specific pig herd. All
      animal models are discussed in this article.

PMID- 8982574
TI  - In utero management of congenital diaphragmatic hernia.
AB  - Fetal surgery offers the possibility of prenatal treatment of congenital
      diaphragmatic hernia (CDH). The in utero management of CDH has evolved with
      continued experimental and clinical experience. Topics covered include the
      experimental rationale and techniques of in utero repair of CDH, methods of
      accurate diagnosis, criteria for patient selection, approaches to ethical
      concerns, operative techniques, and a review of the clinical experience.

PMID- 8982575
TI  - Postnatal management of congenital diaphragmatic hernia.
AB  - The emphasis in postnatal management has shifted from the neonatal surgical
      emergency approach to strategies designed to deal with pulmonary hypoplasia and
      the pulmonary vascular abnormalities. There has been extensive experience with
      alternative ventilation strategies such as ECMO and high frequency ventilation,
      without there being convincing evidence that these have had a major impact on
      mortality. Strategies that emphasize the importance of minimizing ongoing lung
      injury, such as pressure limited (permissive hypercapnia) ventilation and the use
      of surfactant replacement therapy, are beginning to show some encouraging
      results.

PMID- 8982576
TI  - Long-term outlook for survivors of congenital diaphragmatic hernia.
AB  - CDH patients are critically ill but can expect excellent survival if other
      serious anomalies are not present; however, significant long-term morbidities
      exist in the survivors. The most notable of these are developmental delay, poor
      growth, gastroesophageal reflux disease, hearing loss, and musculoskeletal
      abnormalities. Patients require careful long-term follow-up for these problems,
      and caregivers must continue to critically evaluate their medical interventions
      in the neonatal period to try to minimize these morbidities.

PMID- 8982577
TI  - Lessons learned: an editorial from Newport Hospital.

PMID- 8982578
TI  - Atypical cells in effusions: diagnostic value of cell image analysis combined
      with immunocytochemistry.
AB  - The reliable identification of tumor cells in populations of atypical cells
      occurring in body cavity effusions is a well-known diagnostic problem. In order
      to improve tumor cell detection and to predict disease progression, we developed
      a cell scoring strategy based on a combination of DNA cytophotometry and
      immunocytochemistry. For this purpose, morphologically atypical cells obtained
      from 33 effusion samples were submitted to DNA content analysis and tested for
      Ber-EP4 immunoreactivity. It turned out that elevated DNA content alone has a low
      specificity (true negative ratio) and sensitivity (true positive ratio) in
      predicting disease outcome, whereas Ber-EP4 immunoreactivity alone has a high
      specificity (100%) but a low sensitivity (56%). In contrast, the use of a scoring
      system combining the two techniques and relating scores to the previous disease
      state and the cytomorphology of the atypical cells results in highly specific and
      sensitive prediction of the disease outcome. We therefore suggest that this
      approach is a valuable tool for reliably identifying tumor cells in effusions
      containing populations of cytologically suspect cells.

PMID- 8982579
TI  - Upgrading unsatisfactory cervical smears with the MiB-1 method.
AB  - When an unsatisfactory smear (thick inflammatory infiltrate or blood influencing
      the staining characteristics of the epithelial cells) is restained for MiB-1, the
      diagnostic proliferating cells are visualized, and the MiB-1-positive smears can
      be thus upgraded as borderline, grade I, II, and III, corresponding with the
      cytologic diagnoses of, respectively, ASCUS, CIN I, II, and > or = III. In a
      period of 18 months, 2,068 unsatisfactory smears out of a material of 84,817
      smears were restained for MiB-1. In the unsatisfactory group, significantly more
      abnormal smears were detected than in the satisfactory group. Seventy-five of the
      unsatisfactory group were biopsied because of the MiB-1 findings: Three women
      proved to have severe dysplasia, four had carcinoma in situ, and three had
      invasive carcinoma. The per mileage for invasive cervical carcinoma was ten times
      larger in the unsatisfactory group than in the satisfactory group; thus the MiB-1
      method has further enhanced our diagnostic acumen in this difficult type of
      smears.

PMID- 8982580
TI  - Localization of p53 and proliferating cell nuclear antigen in fine-needle
      aspirates of benign and primary malignant tumors of the human breast: an
      immunocytochemical study using supersensitive monoclonal antibodies and the
      biotin-streptavidin-amplified method.
AB  - p53 and proliferating cell nuclear antigen (PCNA) status was determined in fine
      needle aspirates (FNAs) and methacarn-fixed paraffin-embedded tissue sections of
      six fibroadenomas and 50 primary breast carcinomas using supersensitive
      monoclonal antibodies and the biotin-streptavidin-amplified method. Nuclear
      accumulation of p53 was identified in 28% of carcinomas, while a heterogeneous
      immunostaining for PCNA was seen in all benign and malignant tumors examined. p53
      expression in relation to nuclear plemorphism and lymph-node status showed weak
      correlation only as to nuclear grade (r = 0.28; P < 0.01). No direct or inverse
      correlation was found to exist between PCNA score and the evaluated prognostic
      parameters. In conclusion, although the identification of p53 in FNAs of breast
      tumors may assist in the diagnosis of malignancy, its application in the
      laboratory practice of cytopathology appears to be limited, since only 28% of
      primary breast carcinomas accumulate p53. Moreover, PCNA immunocytochemistry can
      be used as an alternative to traditional methods of evaluating the proliferative
      rate of tumors in FNAs.

PMID- 8982581
TI  - Contribution of transmission electron microscopy to fine-needle aspiration biopsy
      diagnosis: comparison of cytology and combined cytology and transmission electron
      microscopy with final histological diagnosis.
AB  - This report evaluates 74 fine-needle aspiration biopsies processed for
      transmission electron microscopy with subsequent surgical procedure. The
      specificity of diagnosis obtained by cytology alone was compared to that obtained
      by cytology and electro microscopy, using histologic diagnosis as the gold
      standard. When cytology gave a diagnosis of malignancy but could not give tumor
      category or type, electron microscopy could correctly give both. When cytology
      could give tumor category but not type, electron microscopy correctly identified
      type in the majority of cases. When cytology gave tumor category and type,
      electron microscopy confirmed the diagnosis. Transmission electron microscopy is
      very helpful when the cytopathologist can diagnose malignancy but cannot give
      tumor category and/or type. When the cytopathologist is specific in his/her
      diagnosis, TEM is not as helpful.

PMID- 8982582
TI  - Atypical parakeratosis: a marker of dysplasia?
AB  - The Bethesda System categorizes atypical parakeratosis (APK) as "ASCUS or SIL
      depending on the degree of cellular abnormalities." APK, however, is not well
      defined. We retrospectively reviewed 68 cervicovaginal specimens with follow-up
      material to identify specific criteria and clinical significance of APK. APK
      cells were small cells, 2-3 times the diameter of neutrophil, with dense,
      orangeophilic cytoplasm, high nuclear cytoplasmic ratio, dense, often uneven
      chromatin, and irregular nuclear contour. Of 62 cases with APK, 37 had
      accompanying dysplastic cells. Of 25 cases with APK alone, follow-up revealed 12
      with squamous intraepithelial lesion (5 HSIL and 7 LSIL) and 13 with benign
      changes. A major diagnostic pitfall of APK was inflammation with degeneration.
      Abundant APK cells, minimal inflammation and degeneration, and previous history
      of dysplasia frequently were associated with follow-up SIL. The findings of this
      study identify APK as an important marker for dysplasia that warrants careful
      evaluation and follow-up.

PMID- 8982583
TI  - Cytopathology of serous neoplasia of the ovary and the peritoneum: differential
      diagnosis from mesothelial proliferations.
AB  - Serous neoplasia of the ovary ranges from benign adenomas through serous
      borderline tumors to invasive serous adenocarcinoma. This spectrum of neoplasia
      is at least partially reflected in the cytomorphologic features of the lesions.
      The objective of this study is to review the cytopathology of serous neoplasia of
      the ovary. In addition, cytologic features of serous surface papillary carcinoma
      and its distinction from peritoneal mesothelial proliferations are discussed.

PMID- 8982584
TI  - Poorly-differentiated adenoid cystic carcinoma: cytologic appearance in fine
      needle aspirates of distant metastases.
AB  - Adenoid cystic carcinoma (ACC) is a primary salivary-gland neoplasm which
      typically yields characteristic cytomorphology upon fine-needle aspiration (FNA).
      We report on the FNA findings of a case of ACC metastatic to the liver which
      demonstrated a predominantly solid, poorly-differentiated pattern, an unusual but
      well-recognized subtype associated with a poor clinical outcome. The FNA findings
      in 7 additional cases of ACC metastatic to distant sites were also reviewed, with
      4 cases displaying a prominent poorly-differentiated component. These findings
      suggest that, although not commonly recognized in salivary-gland FNAs, the poorly
      differentiated pattern of ACC does occur in metastatic deposits and should be
      recognized as such, thereby preventing a needless search for a second primary
      malignancy.

PMID- 8982585
TI  - Cytologic features in fine-needle aspirates from a sclerosing mucoepidermoid
      thyroid carcinoma with eosinophilia.
AB  - Fine-needle aspirates from a sclerosing mucoepidermoid thyroid carcinoma with
      eosinophilia showed peculiar but nonspecific features. The overall picture seems
      more important than individual elements in recognizing this rare entity
      cytologically, since the predominant type of malignant cells has a deceptively
      bland appearance. The differential diagnoses include other primary thyroid
      malignancies, as well as metastatic growth and Hashimoto's thyroiditis.

PMID- 8982586
TI  - Cytomorphology of cystic parathyroid lesions: report of four cases evaluated
      preoperatively by fine-needle aspiration.
AB  - Cystic parathyroid lesions (CPL) account for 1-5% of neck cysts. They are seldom
      palpable; however, they may present as neck swellings that are mistaken both
      clinically and cytologically for thyroid nodules and subsequently referred for
      evaluation by fine-needle aspiration. We present 4 cases of histologically
      confirmed CPL (one simple cyst, one hyperplasia, and two adenomas), 2 of which
      were misdiagnosed as adenomatoid thyroid nodules by fine-needle aspiration.
      Aspirated fluid from one patient was clear and colorless, a classic finding for
      parathyroid cysts, and contained high levels of C-terminal/midmolecule
      parathyroid hormone (CMPH). Fluids obtained from the remaining 3 patients were
      bloody to brown, resembling thyroid cyst fluid. In only 1 of the 3 patients, the
      fluid was analyzed and contained high levels of CMPH. Though cytologic features
      of parathyroid epithelium overlap with those of thyroid epithelium,
      distinguishing features such as unusual cytoplasmic vacuolization and
      granularity, and the absence of colloid, should raise suspicions of a parathyroid
      lesion. Fluid from CPL may not possess the classic appearance; however,
      identification of the subtler cytologic features with knowledge of relevant
      clinical data should prompt analysis of cyst fluid for CMPH, thus confirming the
      diagnosis and avoiding inappropriate therapy.

PMID- 8982587
TI  - Cytopathology of retrograde renal pelvis brush specimens: an analysis of 40 cases
      with emphasis on collecting duct carcinoma and low-intermediate grade
      transitional cell carcinoma.
AB  - We report our experience with 40 retrograde renal brush samples of pelvic
      calyceal lesions with confirmatory tissue studies. On-site cytopathologic
      evaluation was performed in 38 of these specimens. The final histologic diagnoses
      included 24 cases of transitional cell carcinoma (TCC), 17 of which were low
      intermediate grade tumors. All 24 cases were diagnosed cytologically as TCC (22),
      or as suspicious for TCC (2). Three cases classified as collecting duct
      carcinomas were resected; the cytologic specimens in 2 of these cases were
      interpreted as TCC, and one as reactive change. There were three renal cell
      carcinomas (RCC); cytologically, one was considered a papillary neoplasm, one
      suspicious for malignancy, and one as reactive. Two cases of atypical renal cysts
      were reported as suspicious for malignancy in both cytologic and histologic
      material. There was one case of metastatic colon carcinoma identified in the
      brush specimen. Finally, tissue studies in the remaining 7 cases showed
      reactive/inflammatory changes; however, four of the corresponding pelvic brush
      specimens were considered abnormal. A review of the above cases is reported with
      the objective of presenting the cytologic features seen in collecting duct
      carcinoma, low-intermediate grade TCC, and diagnostically difficult cases with
      cyto/histomorphologic discrepancies. The contribution of on-site assessment to
      diagnostic accuracy is also discussed.

PMID- 8982588
TI  - Adenosquamous carcinoma of the bile duct: cytologic features of brush specimens
      from two cases.
AB  - Cytologic brushing is a safe and specific procedure for diagnosing carcinoma of
      the distal bile duct and proximal pancreatic duct. The vast majority of these
      lesions are pure adenocarcinomas. Occasionally, however, other morphologic
      subtypes may be encountered. We report our experience with two adenosquamous
      carcinomas of the bile duct diagnosed by cytologic brushing. Both patients
      presented clinically with jaundice and were found to have mass lesions
      obstructing the bile duct. The brush specimens were cellular and contained a
      mixture of glandular and squamous elements. The glandular component was
      characterized by cohesive aggregates of cells with hyperchromatic, overlapping
      nuclei. The squamous component contained clusters and individual cells with
      hyperchromatic oval-to-spindled nuclei and orangeophilic cytoplasm. Focally, the
      squamous elements appeared to gradually merge into the glandular component, and
      there were clusters of hybrid cells which were difficult to classify as squamous
      or glandular. Although uncommon, these 2 cases demonstrate that the cytologic
      features of adenosquamous carcinoma can be appreciated on cytologic brushing
      specimens.

PMID- 8982589
TI  - Cytologic features of pulmonary malakoplakia related to Rhodococcus equi in an
      immunocompromised host.
AB  - Cytologic features are described in bronchial brushings of a large cavitary lung
      mass from an immunosuppressed patient who had undergone liver transplantation.
      Scattered histiocytes with abundant eosinophilic, vacuolated cytoplasm were noted
      in a background of bronchial cells. Within approximately one fourth of the
      histiocytes, targetoid intracytoplasmic inclusions were present, consistent with
      Michaelis-Gutmann bodies. They were diffusely positive by histo-chemical staining
      with von Kossa, Gomori methenamine silver, and periodic acid-Schiff stains, and
      focally positive with Prussian blue stain. Cultures of the abscess yielded
      Rhodococcus equi. The characteristic microscopic features of pulmonary
      malakoplakia can be discerned in bronchial brushings, and should be sought,
      particularly in immunocompromised patients.

PMID- 8982590
TI  - Cytologic features of deep juvenile xanthogranuloma.
AB  - Juvenile xanthogranuloma (JXG) is a rare lesion of the skin and deep tissues
      whose cytologic features have not previously been published. We report on 2 cases
      of JXG in patients aged 5 days and 5 yr who presented with an axillary mass and
      enlarged supraclavicular lymph node, respectively. Fine-needle aspiration and
      touch imprints made from the surgical biopsies yielded cellular specimens
      composed of histiocytes, multinucleated Touton-type giant cells, and variable
      admixtures of lymphocytes and eosinophils. One lesion was composed primarily of
      benign-appearing histiocytes with admixed multinucleated giant cells and a few
      lymphocytes. The second lesion consisted of a few histiocytes, occasional Touton
      giant cells, many lymphocytes, and scattered fibroblasts. The histiocytes were
      CD68-positive and S100-negative. Histologic follow-up confirmed the diagnosis of
      juvenile xanthogranuloma. One patient was lost to follow-up; the other is alive
      without evidence of recurrence 1 yr after surgery. We conclude that deep JXG has
      characteristic and diagnostic cytologic features.

PMID- 8982592
TI  - Transitional-cell carcinoma metastatic to cerebrospinal fluid: presentation of
      two cases.
AB  - We present 11 specimens from 2 patients with transitional cell carcinoma
      metastatic to the cerebrospinal fluid. This is a rare occurrence documented in
      one previous report in which 5 patients had 28 specimens reviewed (Ehya et al.,
      Acta Cytol 1981;25:599-610). Cytologic features that most likely indicate a
      bladder origin are the cytoplasmic tails and cytoplasmic pseudopod formation.

PMID- 8982591
TI  - Synovial metastasis: diagnosis by fine-needle aspiration cytologic investigation.
AB  - Synovial metastases are a rare occurrence. Only 28 cases have been reported in
      the literature, 10 of which were diagnosed by fluid cytologic evaluation. We
      discuss 2 additional cases in which the diagnosis was made by fine-needle
      aspiration cytologic investigation. The first case is of a 47-yr-old man with
      small-cell carcinoma of the lung metastatic to the right knee joint; the second
      is of a 71-yr-old man with non-Hodgkin's mixed-cell nodular lymphoma also
      involving the right knee joint. The clinical features of these cases are similar
      to previously published instances of secondary synovial tumor, namely in regard
      to sex distribution (14 male and 16 female patients), age range (13-96 yr, mean
      59 yr), and histologic types (adenocarcinoma, 13 cases; squamous-cell carcinoma,
      4; lymphoma, 3; renal clear-cell carcinoma, 3; unknown origin, 2;
      rhabdomyosarcoma, 1; melanoma, 1; chordoma, 1; pulmonary clear-cell carcinoma, 1;
      and Ewing's sarcoma, 1). The condition usually has poor prognosis, with average
      patient survival of < 5 mo.

PMID- 8982593
TI  - Fine-needle aspiration cytology of ovarian cysts in in vitro fertilization
      patients: a study of 125 cases.
AB  - Fine-needle aspiration (FNA) cytology of ovarian cysts, especially in in vitro
      fertilization (IVF) patients, has been only rarely reported. The aim of this
      study was to describe the spectrum of cytological findings seen in FNA specimens
      of 125 ovarian cysts obtained from 84 IVF patients at our institution from 1989
      1993. The Papanicolaou-stained slides made following cytocentrifuge or membrane
      filter preparation were reviewed blindly by two independent pathologists, and the
      consensus diagnoses were compiled and correlated with clinical and radiological
      findings as well as surgical pathology when available. Eight aspirates derived
      from 4 different patients contained neoplastic cells and, of these, one patient
      was later found to have a serous cystadenocarcinoma of low malignant potential,
      while another had a serous cystadenoma. The other 2 patients with neoplastic
      cells in their ovarian aspirates have persistent ovarian cysts that are being
      followed clinically for preservation of fertility. The breakdown of the
      cytological diagnoses of the other aspirates is as follows: 30 follicular cysts,
      5 corpus luteum cysts, and 16 endometriotic cysts. The exact underlying nature of
      66 cysts could not be determined as the aspirates consisted of foamy macrophages
      only. This study demonstrates that the nature of ovarian cysts in IVF patients
      can be determined in many cases by their cytological features, information that
      may help in defining an unsuspected cause for infertility (such as
      endometriosis), and in choosing the most appropriate therapy. This study also
      illustrates that FNA cytology of ovarian cysts can play a role in the detection
      of occult ovarian neoplasms in the IVF patients population.

PMID- 8982594
TI  - Mollaret's meningitis: case report with immunocytochemical and polymerase chain
      reaction amplification studies.
AB  - Mollaret's meningitis is a rare disease with a characteristic clinical course and
      distinctive cerebrospinal fluid (CSF) cytology. Although Mollaret originally
      described the large mononuclear cells seen in the CSF as endothelial, subsequent
      ultrastructural and immunocytochemical studies support a monocyte/macrophage
      lineage for these cells. To data, the pathogenesis of this entity remains
      uncertain, although an association with herpes simplex virus (HSV) has been
      reported in rare cases. In the current case study, immunocytochemistry for factor
      VIII-related antigen, leukocyte common antigen, and macrophage-specific antigen
      were performed and provide additional evidence of a monocyte/macrophage lineage
      for Mollaret cells. Polymerase chain reaction amplification for HSV DNA was done
      to further explore one possible etiology for this disease, but was negative.

PMID- 8982595
TI  - Tumoral calcium pyrophosphate dihydrate deposition disease: cytopathologic
      findings on fine-needle aspiration.
AB  - Tumoral calcium pyrophosphate dihydrate deposition disease (CPPD) is a rare non
      neoplastic entity which mimics primary or metastatic soft-tissue or skeletal
      malignancy. Fewer than a dozen cases have been reported in the literature with
      only histologic descriptions. We present cytologic findings of a unique case of
      CPPD in a 73-year-old black female with a history of end-stage renal disease. A
      fine-needle aspiration (FNA) was done on a 4 x 4-cm neck mass which was
      clinically thought to be malignant. Cytopathologic examination showed numerous
      macrophages with markedly distended cytoplasm and containing multiple yellowish
      orange, short rhomboid crystals. These were strongly birefringent on polarized
      microscopy, consistent with CPPD crystals.

PMID- 8982596
TI  - Fine-needle aspiration biopsy for the diagnosis of lymphoma: a perspective.
AB  - Fine-needle aspiration (FNA) has become a widely used diagnostic tool and it
      remains one of the most rapid and cost-effective methods of assessing a variety
      of pathologic conditions. However, FNA as a method of evaluation of enlarged
      lymph nodes has been approached with a greater degree of caution and reservation,
      largely because Hodgkin's disease and the non-Hodgkin's lymphomas represent a
      diverse group of neoplasms, which is mirrored by a large range of histopathologic
      and cytologic appearances. For these reasons, adjunctive techniques such as
      immunohistochemical staining, cytogenetics, and molecular techniques have been
      introduced to improve the diagnostic accuracy. While such procedures have made
      significant contributions to the identification and typing of lymphomas, there is
      still a requirement for a simple and rapid diagnostic procedure for the patient
      who presents with persistent lymphadenopathy. Light microscopic examination of
      FNA smears fulfills this role, provided its limitations and pitfalls are
      recognised.

PMID- 8982597
TI  - Are eosinophilic structures really a diagnostic cytomorphologic criterion for
      tuberculosis?

PMID- 8982599
TI  - Two-dimensional gel analysis of glandular keratin intermediate filament
      phosphorylation.

PMID- 8982598
TI  - Identification of cytokine-regulated proteins in normal and malignant cells by
      the combination of two-dimensional polyacrylamide gel electrophoresis, mass
      spectrometry, Edman degradation and immunoblotting and approaches to the analysis
      of their functional roles.

PMID- 8982600
TI  - Changes in protein expression during neural development analyzed by two
      dimensional gel electrophoresis.

PMID- 8982601
TI  - Two-dimensional gel protein database of Saccharomyces cerevisiae.
AB  - With the systematic sequencing of the yeast genome, yeast biology has entered a
      new era where novel challenges have to be faced. One challenge is the
      identification of the function of the several hundred novel genes discovered by
      genome sequencing. Another is to understand how all yeast genes act in concert to
      ensure and maintain cell organization. Two-dimensional (2-D) gel electrophoresis
      is the technique of choice to take up these challenges because it provides the
      opportunity of obtaining an overall view of genome expression. In prospect of
      these studies we have undertaken the construction of a yeast 2-D gel protein
      database that contains information on polypeptides of the yeast protein map. In
      this paper we report the information presently contained in this database. The
      reported information includes the identification of 250 protein spots and the
      characterization of polypeptides corresponding to N-terminal acetylated proteins,
      mitochondrial proteins, glucose-repressed proteins, heat shock induced proteins
      and proteins encoded by intron-containing genes. In all, 600 spots are annotated.
      These data can be accessed on the Yeast Protein Map server through the World Wide
      Web network.

PMID- 8982603
TI  - cDNA expression and human two-dimensional gel protein databases: towards
      integrating DNA and protein information.
AB  - The rapid progress in characterizing genes and mRNAs (expressed sequence tags,
      ESTs) as a result of the Human Genome Project makes it imperative to develop
      strategies to interface DNA mapping and sequencing data with protein information,
      as the latter orchestrate most cellular functions. Presently, the only technique
      able to resolve and record the thousands of proteins present in cells and tissues
      is two-dimensional (2-D) gel electrophoresis in combination with computer-aided
      technology to scan the gels, make synthetic images, assign numbers to individual
      spots as well as to enter qualitative and quantitative information. To date,
      comprehensive 2-D gel databases containing information about various properties
      of proteins (cellular localization, identification, regulatory properties,
      partial amino acid sequences, etc.) have been established (available on the
      internet: http:@biobase.dk/cgi-bin/celis). What remains is to provide a link
      between these data and the forthcoming information from the Human Genome Project.
      We are pursuing two approaches to achieve this goal: (i) microsequencing and mass
      spectrometry analysis of proteins resolved from 2-D gels and (ii) expression of
      cDNAs in the vaccinia virus expression system. Using the latter approach we have
      expressed about 60 cDNAs in human cells under conditions that faithfully
      reproduce post-translational trimmings and modifications of the proteins. The
      method, in combination with 2-D gel electrophoresis, allows precise matching of
      almost any cDNA to its protein product, irrespective of the protein abundance.

PMID- 8982602
TI  - High-performance human myocardial two-dimensional electrophoresis database:
      edition 1996.
AB  - The master gel of the human myocardial two-dimensional electrophoresis (2-DE) gel
      database contains about 3300 protein spots characterized in terms of isoelectric
      point (pI) and molecular mass. A high-performance technique was applied, using
      large gels (23 x 30 cm). Isoelectric focusing with anodic sample preparation and
      nonequilibrium running conditions (NEPHGE) was combined with sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in 15% acrylamide gels in
      the second dimension. The range of pI extends from pH 4.5 to 9.6. Seventy
      proteins were identified by combinations of amino acid analysis, N-terminal and
      internal sequencing, immunostaining, matrix assisted laser desorption/ionization
      mass spectrometry (MALDI-MS) peptide mass fingerprinting, post-source decay MALDI
      MS and ladder sequencing by carboxypeptidase P. The identification of additional
      proteins, not found in the master gel, was achieved by immunoblotting.
      Unequivocal identification with high sensitivity and good yield was obtained by
      combining internal sequencing and MALDI-MS. In-gel digestion, the concentration
      and purification of peptides in a peptide collecting device, and the improved
      FRAGMOD program for peptide mass fingerprinting have added to the security and
      sensitivity of identification. The high-performance human myocardial 2-DE
      database was built up with proteins detected by the TOPSPOT program. Spots within
      six sections of the whole pattern are clickable. Protein description includes
      detailed information about identification, characterization, and links to the
      related SWISS-PROT, other 2-DE databases and Medline entries. The database is
      constructed in accordance with four of the rules for a federated database.

PMID- 8982604
TI  - Analysis of chaperonin-containing TCP-1 subunits in the human keratinocyte two
      dimensional protein database: further characterisation of antibodies to
      individual subunits.
AB  - The chaperonin-containing TCP-1 (CCT), found in the eukaryotic cytosol, is
      currently the focus of extensive research. CCT consists of at least eight
      different subunit types encoded by independent but related genes, and a set of
      antibodies that recognise individual subunits has proved useful in the
      characterisation and functional analysis of CCT. These antibodies were used to
      identify subunits of CCT in the human keratinocyte two-dimensional protein
      database. Accurate values for the pI and molecular mass of human CCT subunits
      were determined from the database, and biological data was obtained regarding
      changes in subunit levels in response to extracellular agents and growth
      conditions. The second part of the study describes the characterisation of seven
      monoclonal antibodies raised against mouse TCP-1, also known as CCT alpha, using
      a combination of epitope mapping and immunoblot analysis of protein extracts from
      different species and tissue types. Some antibodies were not monospecific for TCP
      1, and a number of epitope-related proteins were identified.

PMID- 8982606
TI  - Endosomal fractions from viral K-ras-transformed MDCK cells reveal transformation
      specific changes on two-dimensional gel maps.
AB  - We have investigated the effects of viral Kirsten ras oncogene expression in
      Madin-Darby canine kidney (MDCK) II epithelial cell on the differential protein
      expression of organelle proteins. MDCK cells, stably transformed via infection
      with a helper-independent retroviral vector construct, were grown on permeable
      filter supports. Whereas normal cells form highly polarized monolayers, ras
      transformed cells display an unpolarized phenotype, detaching from the substratum
      and developing multilayers (Schoenenberger, C.-A. et al., J. Cell Biol. 1991,
      112, 873-889). We postulate that this breakdown of epithelial polarity reflects
      disturbed intracellular protein transport and sorting, namely, proteins will no
      longer be sorted correctly in intracellular organelles and will therefore not
      reach their appropriate target membrane. Here we emphasize the role of endosomes
      as sorting platform in epithelial cells. We found significant differences in the
      molecular composition of endosomes from normal vs. oncogenic transformed
      epithelial cells, strengthening previous evidence indicating that oncogenic
      transformation results in abnormal expression of normal genes (Celis, J. E.,
      Olsen, E., Electrophoresis 1994, 15, 309-344) as well as the expression of new
      ones (Huber, L. A. et al., Electrophoresis 1994, 15, 468-473).

PMID- 8982605
TI  - Identification of isoprenyl modified proteins metabolically labeled with
      [3H]farnesyl- and [3H]geranylgeranyl-pyrophosphate.
AB  - Here we describe a direct approach for two-dimensional (2-D) gel mapping of
      proteins that are modified by post-translational isoprenylation in mammalian
      cells. Briefly, transformed human amnion cells (AMA) and transfected COS-1 cells
      were metabolically labeled with either [3H]farnesyl-pyrophosphate or
      [3H]geranylgeranyl-pyrophosphate following treatment with lovastatin, which
      blocks the synthesis of mevalonic acid. The proteins were then separated by 2-D
      gel electrophoresis and electrotransferred to nitrocellulose filters. The
      membranes were immersed in dimethyl ether, containing 10% of 2,5-diphenyloxazole
      prior to fluorography. Over 40 [3H]farnesyl-labeled proteins and over 25
      [3H]geranylgeranylated proteins were identified on the 2-D autoradiograms.
      Several [3H]farnesyl-labeled proteins exhibited the same coordinates (M(r) and
      pI) as their [3H]geranylgeranylated counterparts, raising the possibility that
      they may be substrates for both farnesyl and geranylgeranyl transferase(s). The
      approach offers high resolution of both farnesylated and geranylgeranylated
      proteins and it may serve as a powerful tool for the identification of hitherto
      unknown prenylated proteins as well as for the determination of prenylated
      protein levels, type of isoprenoid modification, and possible changes in protein
      prenyltransferase activity.

PMID- 8982607
TI  - Two-dimensional separations of the genome and proteome of neuroblastoma cells.
AB  - Two-dimensional (2-D) electrophoretic methods have been available that allow
      separation of the protein constituents of a cell population. It has also become
      feasible to electrophoretically separate in two dimensions and to display DNA
      fragments derived from genomic digests. Through the appropriate choice of
      restriction enzymes, the functional component of the genome that encompasses CpG
      islands can be preferentially visualized in 2-D gels. The same computerized
      approach for the analysis of 2-D patterns can be applied to investigations at
      either the protein or DNA levels. Our group has utilized 2-D electrophoresis to
      investigate both protein and DNA changes in cancer. The emphasis to date has been
      on the identification of proteins, the abundance of which is related to specific
      biological features of the tumors analyzed and of DNA fragments encompassed in
      genomic amplifications, as the latter commonly contain growth-related genes.
      Findings derived from our analysis of neuroblastoma tumors and cell lines using 2
      D approaches are reviewed. Data for four proteins observed in 2-D gels are
      presented because of our demonstrated association of these proteins with
      differentiation and proliferation properties of neuroblastoma. At the genomic
      level, the detection of amplifications using 2-D gels has necessitated an
      understanding of the variability displayed by multi-copy genomic fragments, which
      we have accomplished to a large part and which we present. An important benefit
      of 2-D approaches is the efficiency of scale and the ease with which abundant
      proteins or multicopy genomic fragments can be detected, identified and
      quantitatively analyzed.

PMID- 8982608
TI  - The use of two-dimensional gel electrophoresis in studies on the role of
      cytoskeletal plaque proteins as tumor suppressors.
AB  - The morphology and functions of cells and tissues are determined, in a large
      part, by mechanical forces generated at cell-cell and cell-extracellular matrix
      (ECM) contacts. At these sites, transmembrane adhesion receptors of the integrin
      and cadherin families are linked, via their cytoplasmic domain, to the
      cytoskeleton by submembranal plaque proteins such as vinculin, alpha-actinin and
      the cell-cell junctional plaque proteins alpha- and beta-catenin and plakoglobin
      (or gamma-catenin). Recent studies have implicated this link of structural
      molecules between the outside and inside of the cell in signal transduction. We
      have shown that the expression of junctional plaque proteins is modulated during
      growth stimulation and differentiation, and is dramatically reduced in certain
      tumor cells. To study the functional significance of these changes in expression,
      we have used recombinant DNA technologies to overexpress or suppress the levels
      of junctional plaque proteins. In addition, we eliminated the expression of
      vinculin in embryonal stem (ES) cells and in the embryonal carcinoma F9 line by
      gene disruption employing homologous recombination. The results have indicated
      that moderate overexpression of cell-ECM plaque proteins results in reduced cell
      motility. In contrast, suppression of their expression, by antisense
      transfection, led to enhanced motility and conferred anchorage independent growth
      and tumorigenicity, upon injection into nude mice. These findings suggest that
      submembranal plaque proteins can act as effective tumor suppressors. In agreement
      with this notion, we found in several tumor cell lines diminished levels of
      junctional plaque proteins. Restoration of their level to that found in normal
      cells resulted in tumor suppression after their injection into experimental
      animals. Here we demonstrate the usefulness of the application of two dimensional
      (2-D) gel electrophoresis in these studies.

PMID- 8982610
TI  - Analysis of phosphorylated isoforms of the p53 tumor suppressor protein in human
      lung carcinoma cells undergoing apoptosis.
AB  - The expression of p53 tumor suppressor protein isoforms in H460a cells induced to
      undergo apoptosis by 2-methoxyestradiol was investigated by two-dimensional gel
      electrophoresis. Whole-cell proteins from control and apoptotic H460a cells were
      separated by two-dimensional electrophoresis and were transferred to
      nitrocellulose. The p53 isoforms were detected by immunoblotting using p53
      monoclonal antibody Bp53-12. Four isoforms of p53 (2, 3, 5, and 6) differing in
      phosphorylation state were detected in control cells. Three additional isoforms
      (1, 4, and 7) were observed to be expressed at significant levels only in
      apoptotic cells. The differential expression of isoforms 1, 4, and 7 in apoptotic
      cells suggests that one or more specific phosphorylation events generating these
      forms of p53 could play a role in regulating the function of p53 in apoptosis.

PMID- 8982609
TI  - Tumor suppressor p53 gene forms multiple isoforms: evidence for single locus
      origin and cytoplasmic complex formation with heat shock proteins.
AB  - The tumor suppressor protein p53 is a major cell cycle control factor, and
      mutations in p53 are the most common genetic lesion found in human tumors,
      resulting in loss of function and contributing to malignant transformation. This
      report reviews several studies which show that p53 protein appears as at least
      eleven isoforms having the same amino acid backbone but varying in charge by
      level of phosphorylation. All isoforms are derived from a single locus, which
      indicates that p53 activity is modulated by post-translational modification. In
      addition, mutant p53 forms hetero-oligomers with two families of proteins: HSP70
      and a 90 kDa group similar to HSP90. Cytoplasmic complexes are most likely formed
      to protect p53 from proteolysis and are probably involved in translocation of
      activated p53 from the cytoplasm to the nucleus for transactivation of other cell
      cycle control genes.

PMID- 8982611
TI  - ADP-ribosylation of actins in fibroblasts and myofibroblasts by botulinum C2
      toxin: influence on microfilament morphology and migratory behavior.
AB  - Actins comprise six isoforms of which the nonmuscle isoforms beta-/gamma-actins
      are expressed by all eukaryotic cells. The expression pattern of one of the
      muscle actin isoforms, alpha-sm actin, previously believed to be restricted to
      smooth muscle, has been broadened to encompass activated fibroblasts
      (myofibroblasts) as well. The significance of this molecular conversion has
      remained largely unknown. We have recently shown that a reduction in filamentous
      alpha-sm actin by electroinjected specific antibodies or antisense
      oligodeoxynucleotides leads to increased motility in breast myofibroblasts
      (Ronnov-Jessen, L., Petersen, O. W. J. Cell Biol. 1996, 134, 67-80). In the
      present study we have expanded on the functional significance of actin isotypes
      in fibroblasts from the opposite point of view, namely filamentous nonmuscle
      actin. Nonmuscle actins in fibroblasts and myofibroblasts were ADP-ribosylated by
      Clostridium botulinum C2 toxin. The substrate for C2 toxin is globular actin,
      which upon ribosylation cannot incorporate into microfilaments. The pattern of
      actin ADP-ribosylation in (myo)fibroblasts in the presence of [32P]NAD was
      analyzed by isoelectric focusing, fluorography and immunoblotting. The influence
      of C2 toxin on microfilaments in intact cells was further assessed by
      immunofluorescence, and motility was measured in a mass migration assay and by
      computerized video time-lapse microscopy. We show here that C2 toxin specifically
      ribosylates beta- and gamma-actin in both fibroblasts and myofibroblasts. Whereas
      fibroblasts rapidly round up and stop migrating when filamentous beta-/gamma
      actin is reduced by short-term ADP-ribosylation, myofibroblasts maintain their
      flattened morphology and a basic low motility.

PMID- 8982612
TI  - Use of two-dimensional gel electrophoresis to characterize protein synthesis
      during neuronal death in cerebellar culture.
AB  - Two-dimensional gel electrophoresis was performed to further investigate the
      biochemical changes in protein synthesis observed in two neuronal death models,
      induced respectively by cytosine arabinoside and glutamate. These drugs induced,
      respectively, apoptotic and necrotic types of cell death in cerebellar cultures,
      as previously reported. Most of the proteins showed decreased labeling after
      toxic exposure, as expected, but some polypeptides showed increased labeling or
      appeared to be newly synthesized. The identification of these polypeptides and
      their implication in neuronal death are discussed.

PMID- 8982613
TI  - Expression and divalent cation binding properties of the novel chemotactic
      inflammatory protein psoriasin.
AB  - Psoriasin is a novel chemotactic inflammatory protein that possesses weak
      similarity to the S100 family members of Ca(2+)-binding proteins, and that is
      highly up-regulated in hyperproliferative psoriatic keratinocytes. Here we have
      used the psoriasin cDNA to express recombinant human (rh) psoriasin in
      Escherichia coli as a fusion protein containing a hexa His tag and a factor Xa
      cleavage site in the NH2-terminus. The protein was purified by affinity
      chromatography on Ni(2+)-nitrilotriacetic acid agarose, digested with factor Xa,
      further purified by ion-exchange chromatography and characterized by two
      dimensional (2-D) gel electrophoresis and NH2-terminal sequencing. The ability of
      rh psoriasin to bind Ca2+, Zn2+, and Mg2+ was determined by dialysis experiments.
      We found that rh psoriasin may bind at least seven molecules of Ca2+ in KCl and
      several molecules in NaCl, with an affinity for the first bound molecule of 1.3
      1.6 x 10(4) M-1. This indicates that psoriasin may cooperatively bind several
      molecules of Ca2+ when present in the extracellular space, or putatively, if
      localized in subcellular compartments where the concentration of Ca2+ is
      relatively high. At least eight molecules of Zn2+ were bound in KCl and four in
      NaCl, with an affinity just below 1 x 10(4) M-1 for the first molecule. Thus
      psoriasin does not bind significant amounts of Zn2+ at physiological
      concentrations. Mg2+ and Ca2+ are bound anti-cooperatively and binding of each of
      the ions (Ca2+, Zn2+, or Mg2+), is accompanied by conformational changes that
      move tyrosine residues to more hydrophobic areas.

PMID- 8982615
TI  - Trends of the characteristics and appropriateness of admissions to acute
      geriatric and medical wards in Italy from 1988 through 1993. Gruppo Italiano di
      Farmacovigilanza nell'Anziano--GIFA.
AB  - Recent modifications in the health care system in Italy reduced the number of
      inpatient care beds and limited the access to outpatient services while the
      proportion of older persons increased. To assess the burden of these changes on
      hospital care the characteristics of admissions to 35 acute geriatric wards and
      31 internal medicine wards in Italy were studied between 1988 and 1993. All
      patients admitted during 4 months in 1988, 1 month in 1991 and 4 months in 1993
      were enrolled in the study. The appropriateness of admission was assessed by
      means of the Appropriateness Evaluation Protocol criteria. The Charlson
      comorbidity index score was used to quantify comorbidity. Between 1988 and 1993,
      18,790 patients were studied. The mean age increased from 67.9 +/- 0.2 to 71.7 +/
      0.2 years (p < 0.0001), the mean number of drugs taken during hospital stay
      increased from 5.2 +/- 0.0 to 5.5 +/- 0.0 drugs (p < 0.0001), the mean Charlson
      comorbidity index score increased from 1.33 +/- 0.02 to 1.50 +/- 0.03 (p <
      0.0001) and the mean length of stay decreased from 17.6 +/- 0.2 to 16.1 +/- 0.2
      days (p < 0.0001). The rate of appropriate admissions increased from 68.6% to
      85.5% (p < 0.0001). Consistent results were found when the data were stratified
      according to gender and type of ward. It was concluded that in Italy,
      concurrently to an increased load of hospital care, inappropriate admissions
      diminished over time. These data show that the need for geriatric care is
      increasing.

PMID- 8982614
TI  - Do we believe what patients say about their neoplastic symptoms? An analysis of
      factors that influence the interviewer's judgement.
AB  - In order to analyze factors that influence an interviewer's judgement of the
      validity of responses given by patients on the duration of their neoplastic signs
      and symptoms, 183 consecutive symptomatic patients hospitalized for a digestive
      tract neoplasm were personally interviewed. The validity of the answers was
      judged by the interviewers to be high in 156 cases (85%), and low in 27 (15%).
      The subjective validity of the interview (SVI) was inversely related to the time
      elapsed from first medical symptom to interview (TFMSI), even after adjusting for
      the duration of the interview (p < 0.05). SVI was not influenced by whether
      patient and interviewer agreed on the first symptom. SVI was inversely related to
      educational level (p < 0.01) and to occupational class (p = 0.04). Patients whose
      Karnofsky's Index (KI) was > or = 80 were over twice as likely to yield valid
      responses (TFMSI-adjusted odds ratio [OR] = 2.82, p = 0.037). Multivariate
      analyses selected education, TFMSI and KI as independent predictors of the
      interviewer assessment. The SVI of patients admitted to the hospital through the
      Emergency Department was lower than that of subjects whose admission was planned
      (OR = 6.49, p = 0.005). In this study SVI related in a logical manner to the
      characteristics of the interview, of the subjects and of their clinical course.
      It hence appeared to reasonably estimate the validity of data collected.
      Identifying factors that affect the reliability of patients' responses would help
      increase the validity of studies on the duration of cancer symptoms.

PMID- 8982616
TI  - Marital status as a predictor of survival in idiopathic dilated cardiomyopathy:
      the Washington, DC dilated cardiomyopathy study.
AB  - Marital status and other socioeconomic and clinical factors were examined as
      predictors of survival in idiopathic dilated cardiomyopathy using data from a
      hospital-based study in Washington, DC. Twenty-five (18.1%) of the cases (n =
      138) were single, 66 (47.8%) were married, 25 (18.1%) were divorced or separated,
      and 22 (15.9%) were widowed. Married patients were more likely to be male, to
      have an annual household income greater than $15,000, and to live with another
      person (p < or = 0.01) as compared with those who were single, widowed, divorced
      or separated. Widowed patients were older on average and more likely to abstain
      from drinking alcohol. The cumulative survival among widowed patients at 12 and
      24 months was 54.6 and 48.5%, respectively, as compared with 75.8 and 59.0% among
      single patients and 80.0 and 71.2% among married patients. The survival of
      divorced or separated patients was relatively good with a cumulative survival of
      84.0% at both 12 and 24 months. Older age, lower ejection fraction, ventricular
      arrhythmias, bundle branch block, and marital status were significant predictors
      of survival in univariate analysis using the proportional hazards model. In
      multivariable analysis, age, race, ejection fraction, and marital status were
      statistically significant independent predictors of survival, with single
      patients with idiopathic dilated cardiomyopathy having a poorer survival than
      those who were married (adjusted RR = 2.5, 95% CI 1.1-6.2, p < 0.05). The
      observed association with marital status may be explained by psychosocial factors
      not examined in the present study such as quality of social network or
      psychological stress.

PMID- 8982617
TI  - Factors associated with asthma in school children.
AB  - To investigate the factors associated with asthma in school children, a case
      control study of 203 asthmatic and 203 non-asthmatic children (103 males and 100
      females in each group) aged 6 to 18 years, was organized during the period
      September 1992 to May 1993 in Al Ain city, United Arab Emirates. Cases comprised
      known asthmatic children who were regularly receiving medication for asthma and
      were confirmed as asthmatics by a physician. Cases and controls were matched by
      age and sex. A questionnaire was used to obtain information about respiratory
      illnesses (pneumonia, bronchitis, bronchiolitis, sinusitis and croup); atopy
      (allergic rhinitis and atopic dermatitis) and familial allergic diseases
      (parental asthma and atopy). Information about socioeconomic status and
      limitations to children as a result of asthma were also obtained. Logistic
      regression analysis showed that bronchitis, atopy (allergic rhinitis and atopic
      dermatitis), croup, parental asthma and parental atopic dermatitis were
      significant risk factors for childhood asthma after adjusting for other
      confounding covariates. The model also showed that parental asthma (p < 0.0001)
      is much more influential than parental atopic dermatitis (p = 0.01) as a risk
      factor for asthma. Although pneumonia and sinusitis were significant risk factors
      when analyzed univariately, they were not significant after adjusting for other
      covariates. Bronchiolitis, smoking and socioeconomic status were beyond the reach
      of statistical significance as risk factors to asthma in our sample.

PMID- 8982618
TI  - Possible correlation between low antigenic drift of A(H1N1) influenza viruses and
      induction of HI antibodies.
AB  - This study examined whether, during a seven-year period of low A(H1N1) influenza
      virus antigenic drift (1988-1989 and 1994-1995, winters), humoral antibody
      response of elderly volunteers to influenza vaccines could suggest a lack of
      antibody pressure for drift. In all the years studied A/Taiwan/1/86, the A(H1N1)
      vaccine component, had a low ability to induce protective hemagglutination
      inhibiting (HI) antibody titres (> or = 1:40). However a similar low
      immunogenicity was found for some of the different A(H3N2) strain variants of
      influenza virus, co-circulating in the same period and showing a regular extent
      of antigenic variations. Although our data could be at least in part explained by
      the type of study population (elderly and repeatedly vaccinated), postepidemic
      serological studies did not evidence a consistently lower ability in mounting
      protective immune response in elderly people as compared with younger against the
      influenza strains studied. Therefore, our present results did not exclude a true
      low immunogenicity of A/Taiwan and of some A(H3N2) influenza strains, circulating
      in the winters examined. This suggests that, besides the necessity to evade prior
      immunity, additional factors could influence the frequency of influenza viruses
      antigenic drifts.

PMID- 8982619
TI  - Prevalence of dementia among elderly people in Troina, Sicily.
AB  - We performed a two-stage survey on the prevalence of dementia among people aged
      over 74 in Troina, northern Sicily, Italy. During the first stage people were
      screened by the Mini Mental Status Examination (MMSE), previously validated in
      our population for the cut-off score with 100% sensitivity and the best
      specificity to diagnose dementia. During the second stage people scoring 19 or
      less at the MMSE test were invited to be examined by a neurologist who diagnosed
      dementia according to DSM-III R. Out of 365 subjects of the initial sample 347
      were screened by MMSE test and 163 scored 19 or less. Of these, 135 were
      neurologically and neuropsychologically examined in the second stage, and 80
      proved to be demented. The minimal estimate of prevalence of dementia in our
      sample was 21.9% (21.9% men, 21.8% women). The poor education and psychosocial
      life may be the underlying condition favoring dementia in this sample of elderly
      people.

PMID- 8982620
TI  - Population-based study of emergency department admissions and deaths from
      injuries in Barcelona, Spain: incidence, causes and severity.
AB  - The aim of this study was to estimate the incidence of morbidity and mortality
      due to injuries in the population over the age of 14 years in Barcelona, Spain.
      Injury distribution according to sex, age, external cause, place of occurrence of
      the injury and severity was also obtained. A one-year survey was conducted in the
      emergency departments of the six main hospitals in Barcelona, based on a
      multistage sampling. Information was collected prospectively in emergency
      services by specially trained non-staff interviewers. Mortality data were drawn
      from death certificates. The incidence rate was 74.7 injury cases per 1,000
      person-years over 14 years of age, higher in males than in females. Injury rates
      were highest in the youngest age-group and progressively lower until people over
      75 years of age. Main external causes of injury were falls, being struck or
      caught by objects, and traffic-related injuries. The leading specific causes of
      injury mortality were traffic injuries, suicides and poisonings. While the
      overall admission incidence was 3.34 cases per 1,000 inhabitants, the proportion
      of hospitalized cases was 45.0 per 1,000 injury cases admitted to emergency
      rooms, higher for females, for traffic injuries and in the elderly population.
      Ninety-six percent of injury cases had an ISS value of 8 or less, mean ISS being
      highest for traffic injuries and falls. Injury morbidity and mortality amongst
      residents of Barcelona follow sex, age and cause of injury patterns which are,
      overall, comparable to those observed in other industrialized countries,
      suggesting that similar etiologic factors might be operating in those areas. The
      results should enable the orientation of injury prevention policies in the urban
      environment targeted on the young and the elderly population.

PMID- 8982621
TI  - Evaluation of prenatal diagnosis of congenital gastro-intestinal atresias.
AB  - Prenatal diagnosis performed by fetal ultrasound scan is now a routine part of
      antenatal care in many countries. That an increasing number of fetal anomalies
      may be detected on prenatal ultrasound is beyond doubt. However what is
      theoretically possible is not, always done in practice specially when
      gastrointestinal atresias (GIA) are concerned and when whole antenatal
      populations are screened rather than high risk groups. Thanks to our registry of
      congenital anomalies a retrospective study was undertaken to evaluate the
      prenatal detection of GIA by ultrasound scan in 118,265 consecutive pregnancies
      of known outcome. Only 31 out of 129 malformed fetuses with GIA were detected
      (24.0%). The sensitivity of detection varied from 51.4% for atresia of the small
      intestine to 24.2% for esophageal atresia and 8.2% for ano-rectal atresia. No
      isolated case with esophageal atresia and ano-rectal atresia were diagnosed. Our
      results stress the need to perform scans at > or = 18 weeks gestation and to
      train sonographers in order to improve prenatal detection of GIA.

PMID- 8982622
TI  - Subjectively experienced symptoms in relation to socio-economic factors in women.
AB  - As observed in a cross-sectional population study of 1,302 women, aged 44-66
      years and representative of middle-aged women living in a Swedish city, symptoms
      and complaints were found to be unevenly distributed in the female population.
      Factors such as foreign origin, low education, different kinds of isolation such
      as not working outside of the home, being divorced or widowed seemed to be
      factors which increased the risk of experiencing different symptoms and
      complaints. When meeting a patient with a complaint it is important to take all
      possible causes into consideration including socio-economic factors.

PMID- 8982623
TI  - Epidemiology of human T-lymphotropic virus type II (HTLV-II) infection in Spain.
      HTLV Spanish Study Group.
AB  - The human T-lymphotropic virus type II (HTLV-II) has recently been associated
      with the genesis of some subacute neurological syndromes and, rarely, with
      atypical T-lymphoid malignancies. The virus is endemic in some Amerindian and
      African tribes, and among intravenous drug users (IDUs) in North America and
      Europe. Given that HTLV-II is transmitted by the same routes as other human
      retroviruses, the screening of antibodies to HTLV-II in blood donors has became a
      matter of controversy in some countries. Herein, we describe the clinical,
      epidemiological and virological features of 113 individuals with HTLV-II
      infection identified in Spain up to September 1995. Most of them (94/113; 83%)
      were male, and all but seven were natives. Four were African immigrants living in
      Madrid and 3 had been born in other European countries. All but six subjects were
      IDUs, and sexual transmission of HTLV-II and transfusion were involved in five
      and one individual, respectively. Eighty-four percent of the IDUs infected with
      HTLV-II were co-infected by HIV-I (93/107). Clinical manifestations potentially
      linked to HTLV-II were absent, although an IDU male co-infected by HIV-1 and HTLV
      II developed a severe non-inflammatory proximal myopathy. In conclusion, HTLV-II
      infection is present in Spain, mainly among IDUs, with a growing incidence and a
      current overall prevalence of 2.0 percent.

PMID- 8982624
TI  - Periodontal disease, oral microbial flora and salivary antibacterial factors in
      diabetes mellitus type 1 patients.
AB  - One hundred and thirty-one patients with diabetes mellitus type 1 (IDDM) and 20
      healthy controls were checked for the presence of periodontal diseases and for
      some oral microbiological parameters. Results demonstrated that IDDM patients,
      who were well compensated from both the metabolic and clinical point of view,
      showed a prevalence for periodontopathies, which only differed slightly from
      controls. Only the presence of gingivitis was significantly higher in IDDM
      patients than in healthy subjects. Both anaerobic and aerobic microbial flora did
      not show substantial differences for either group. Among the salivary
      antibacterial factors studied, lysozyme was significantly decreased in diabetic
      patients compared to controls. It is concluded that IDDM patients undergo
      periodontal complications with a frequency quite close to that of non-diabetic
      healthy subjects, when the disease is under strict metabolic and clinical
      control.

PMID- 8982626
TI  - Evaluation of penicillin susceptibility in clinical isolates of Streptococcus
      pneumoniae oxacillin resistant.
AB  - Antibiotic resistant pneumococci have been reported from all continents. Because
      of the importance of pneumococci in the aetiology of life-threatening diseases,
      the screening for penicillin resistance with oxacillin disc on all clinically
      significant isolates is suggested. However, discrepancy between the determination
      of penicillin resistance by oxacillin disc diffusion and the determination of
      penicillin minimum inhibitory concentration (MIC) has been reported. On this
      basis we have examined seven strains of Streptococcus pneumoniae isolated from
      patients recovered for the exacerbation of chronic bronchitis which were
      oxacillin-resistant. The assay of penicillin MICs showed that three isolates were
      moderately resistant to this agent, while four isolates resulted sensitive to
      penicillin as well as to cefotaxime. These results suggest that a further
      evaluation of penicillin MIC should be performed on those strains of S.
      pneumoniae resulting oxacillin-resistant.

PMID- 8982627
TI  - The modification in measles vaccination age as a consequence of the earlier
      decline of transplacentally transferred antimeasles antibodies in Turkish
      infants.
AB  - The maternal antibodies are gradually decreased at 9 to 12 months in infants. We
      determined the elimination period of maternal measles antibodies in 34 infants
      whose mothers had had a history of natural measles previously. Seropositivity
      rates at sixth and nine months of age were found to be 61.8% and 3.4%,
      respectively. The very low passive antibody at nine months of age may suggest the
      measles vaccination could be carried out earlier than just before the critical
      age of antibody level.

PMID- 8982625
TI  - Molecular and phage typing of Staphylococcus aureus harbouring cryptic
      conjugative plasmids.
AB  - The spread of antibiotic resistant-bacterial pathogens in a hospital could be due
      to the spread of a resistant strain or the spread of a resistance plasmid among
      unrelated strains. In this study the relatedness of Staphylococcus aureus
      isolates carrying identical cryptic conjugative plasmids was determined by a
      combination of resistance profiles, plasmid patterns, pulsed field gel
      electrophoresis of SmaI digested chromosomal DNA and phage typing. Results of the
      different typing techniques were in agreement to one another and demonstrated
      that the isolates were of three different types. The results suggested that a
      cryptic conjugative plasmid had spread to different S. aureus isolates in the
      hospital. This is an example of plasmid spread as opposed to strain spread.

PMID- 8982628
TI  - Detection of Brucella melitensis by BACTEC NR 730 and BACTEC 9120 systems.
AB  - In many parts of the world, brucellosis has significantly decreased, but it is
      still a problem in some regions of Turkey. In our laboratory we have isolated 58
      Brucella spp. through BACTEC NR 730 and 30 Brucella spp. through BACTEC 9120
      systems. 31 of the 58 isolates were detected by BACTEC NR 730 system in 72 hours.
      The majority of the growth values were between 45-65. BACTEC 9120 system detected
      all the isolates in 84 hours.

PMID- 8982629
TI  - Neisseria gonorrhoeae RNA/DNA hybridization and culture for screening of
      gonococcal infections in a low-prevalence population.
AB  - Gonorrhea is still a major sexually transmitted disease (STD) worldwide. Its
      etiologic diagnosis is based on identification of the causative agent, Neisseria
      gonorrhoeae, by culture of genital secretions, which is often hampered by
      difficulties of sample collection and transport. Alternatively, nucleic acid
      hybridization techniques for routine diagnosis of N. gonorrhoeae appear to be
      useful by eliminating problems associated with bacterial viability, particularly
      for surveillance of low-prevalence populations. Our study among 1,508 outpatients
      undergoing routine examination for common STDs used RNA/DNA hybridization with a
      DNA probe specific for N. gonorrhoeae (Gen Probe Pace 2) and classical culture.
      Of the 1,750 specimens tested, 12 were positive by DNA probe and culture. In 8
      cases, only DNA probe was positive while culture was negative. In 3 of these
      discrepant cases clinical and epidemiological data suggested true N. gonorrhoeae
      infection. Thus, DNA probe assay for N. gonorrhoeae may greatly improve screening
      of N. gonorrhoeae among low-prevalence populations. However, culture remains
      mandatory for testing antimicrobial resistance of these highly communicable
      infectious agents.

PMID- 8982630
TI  - Tetanus and injections drug use: rediscovery of a neglected problem?

PMID- 8982631
TI  - Changing incidence of peptic ulcer in Germany.

PMID- 8982632
TI  - A cluster of cancer deaths among wastewater treatment workers.

PMID- 8982633
TI  - Establishment of an embryonic stem cell line from 8-cell stage mouse embryos.
AB  - The aim of this study was to try establishing mouse ES cell lines from the early
      developmental stage. Fifty-two uncompacted 8-cell stage embryos were dissociated
      and single blastomeres were seeded on primary embryonic fibroblasts in DMEM/F12
      completed with 10% foetal calf serum, 10% new born calf serum. 10(-4) M beta
      mercaptoethanol. After approximately 5 days of culture, multiple cell clones
      exhibiting stem cell morphology grew out and were dissociated. One cell line was
      established (MSB1) and characterised. The karyotype and the G-banding revealed a
      male diploid cell line. MSB1 cells were injected into syngenic mice and produced
      teratocarcinomas. Detailed histological examination of the tumours showed a great
      variety of cell types including representatives of all three primary germ layers.
      Several nests of undifferentiated stem cells were also present. Microinjections
      of MSB1 cells into 52 blastocysts produced 2 chimeras, 1 male and 1 female. These
      results demonstrate that a highly pluripotents ES cell line can be derived from 8
      cell stage mouse embryos. However, the male chimera appeared sterile. More
      experiments would thus be necessary to prove that the cell line obtained is
      capable to colonise the germ line.

PMID- 8982634
TI  - Is the subzonal-insemination procedure an efficient technique in the treatment of
      extreme oligoasthenoteratozoospermia?
AB  - OBJECTIVES: The present study evaluates the usefulness of the sub-zonal
      insemination (SUZI) for patients with previous IVF failures or affected by severe
      oligoasthenoteratozoospermia and the necessity of pre-treatment semen analysis.
      DESIGN: Twenty-five patients underwent 43 cycles of either SUZI or alternate
      SUZI/IVF procedures according to semen characteristics. RESULTS: Among the 571
      retrieved oocytes, 398 were microinjected and 173 were treated by IVF. Among the
      microinjected oocytes, 19% fertilized (12% 2PN: 7% 3PN) and 96% of the 2PN
      oocytes developed into embryos. Thirty-one embryo transfers were performed, 8
      pregnancies were obtained and 7 embryos were cryopreserved. The 2 PN rates in
      SUZI and IVF procedures in the same cycle were not significantly different. The
      analysis of the different semen samples obtained before and during the treatment
      reveals that the semen quality varies in such a way that the decision of the
      adequate microinjection strategy to follow should only be taken according to the
      semen quality at the day of treatment. CONCLUSION: SUZI is not a satisfactory
      technique for treatment neither in case of previous IVF failures nor for severe
      oligoasthenoteratozoospermia.

PMID- 8982635
TI  - Further analysis of developmental potentialities expressed by the footplate of 11
      day mouse embryo hindlimb buds explanted in organ culture.
AB  - The developmental potentialities expressed in vitro by hindlimb buds or excised
      footplates of 11-day mouse embryos have been analyzed using different kinds of
      organ culture procedures. As compared with unsatisfactory results obtained with
      explants transferred in submerged culture, others cultured on Nuclepore membranes
      following the Trowell technique exhibited growth and pattern formation
      performances which could be correlated with the CR length of their donor embryos.
      According to the case, their distal segment appeared hypotrophic and strongly
      necrotic, triangular shaped with 2 or 3 converging digital rays, four toed shaped
      with 3 or 4 digital rays, and pentadactylous. Insufficient distal morphogenesis
      observed in younger limb buds could be related to selective cell death in the
      A.E.R. and subridge mesoderm, as well as to early dilation of the marginal vein.
      Prospective area of digit 1 proved to be particularly sensitive to culture
      conditions. However, observations made in explants excised from potentially
      polydactylous embryos showed that the X-linked polydactyly (Xpl) phenotype can be
      expressed in vitro. Three technical variants contributed to improve the quality
      of pattern formation in the distal segment: the use of collagen-coated nuclepore
      membranes and the addition of bFGF or TGF-beta in the culture medium. The
      presence of bFGF seems to provide a protection against mesodermal cell death;
      that of TGF-beta appeared to promote digital outgrowth. The preskeletal pattern
      achieved in cultured footplates was in good agreement with maps of prospective
      areas previously established for the mouse hindlimb bud.

PMID- 8982636
TI  - Ultrastructural and histochemical characteristics of the lateral oviducts of
      Baculum thaii Haus. (Phasm.).
AB  - The wall of the lateral oviducts of baculum thaii is composed of a monolayered
      epithelium, lacking a cuticular intima, which lies on a sheath of striated
      muscular fibres. Untreated oviductal specimens exhibit two distinct regions. The
      anterior region, into which the various ovarioles emerge, is opalescent. The
      posterior region is more dilated and darker in colour. On the basis of the
      ultrastructural characteristics of the epithelial cells, four successive zones
      are definable for each oviduct. The first two zones comprise the most anterior
      oviductal area while the third and fourth comprise the posterior region. In zone
      1 only is the oviductal wall composed of a single cell type. In addition,
      differences in structural organization between mated and virgin females were
      observed in this zone alone. In the three remaining zones, two distinct cell
      types were distinguishable according to two models of fundamental organization:
      cells having numerous apical microvilli and dome-shaped cells. The results of
      histochemical analyses established that the abundant secretory product elaborated
      by the epithelial cells is rich in both proteins and predominantly acidic
      mucosubstances. The histochemical characteristics of the secretory product
      differentiate significantly not only between the four zones in the same
      individual but also when the corresponding zones are compared in the mated and
      virgin females.

PMID- 8982637
TI  - Atrial natriuretic factor (ANF)-like immunoreactivity and secretory granules in
      internal gills tadpoles of South American toad Bufo arenarum (Hensel).
AB  - In this study, an ultrastructural and immunohistochemical analysis was carried
      out on the presence of Atrial Natriuretic Factor-like substance in the internal
      gills of premetamorphic larval stages of the South American toad. The results of
      immunohistochemical study indicate that, at larval 27 and following stages, ANF
      like immunoreactive cells are seen in internal gills. At electron-microscopy
      level "secretory granules" similar to those ANF-immunoreactives granules of
      myoendocrine cells of the same species are seen only in clear cells of gill
      rakers. Our results reveal the occurrence of ANF-like substance in Bufo arenarum
      gills and may suggest that "cardiac hormones" might play a paracrine and/or
      autocrine role in the water and electrolyte balance at internal gills level.

PMID- 8982639
TI  - Abnormal cutaneous nerve outgrowth: a secondary effect of methyl triazene
      teratology in developing mouse limb buds.
AB  - The cutaneous branches originating from the superficial distal division of the
      ulnar nerve exhibit abnormal developmental features in 70.2% of the forelimb buds
      from embryos submitted 2 or 3 days earlier to methyl triazene administered to
      their pregnant mother. Similar abnormalities characterize the preaxial ventral
      cutaneous nerve of the thumb in 17.8% of forelimb primordia. The affected nerves
      undergo anticipated growth with respect to the normal schedule, follow abnormal
      pathways through areas of extensive cell death, and finally reach the apical
      ectoderm where they run in close contact with the basement membrane without
      forming a plexus. Histological observations gathered in pyronin-methyl green
      stained serial sections as well as in whole limb buds after cholinesterase method
      suggest that three factors probably contribute to modify nerve outgrowth: (1) a
      discrepancy between the rate of nerve progression and that of mesodermal growth
      in the prospective zeugopod territory which is preferentially affected by the
      teratogen; (2) facilitated nerve pathfinding into areas strongly hit by triazene
      induced mesodermal cell death; and (3) alteration or abolition of some unknown
      ectodermal influence necessary to stimulate selective guidance of terminal
      sensory afferents and to maintain them transiently at some distance from the
      epidermis.

PMID- 8982638
TI  - Comparison between two HNK-1-related antibodies immunoreactivity (HNK-1-anti-leu
      7 and anti-HNK-1/N-CAM) during rat cephalogenesis.
AB  - The fixation sites of two antibodies, HNK-1-anti-leu 7 and anti- HNK-1/N-CAM,
      were studied during visceral cephalogenesis in the rat. The labelling patterns of
      both antibodies were different. Anti-leu 7 staining was restricted to trunk
      neural crest cells, the peripheral nervous system, myotomes and premuscular
      cells, the eye rudiment and the olfactory vesicle. On the other hand, anti- HNK
      1/N-CAM extended to the otocyst, several epithelia (including tooth germs) and
      precartilages. Anti-HNK-1/N-CAM staining of somites and cranial nerve ganglia was
      more precocious than anti-leu 7 labelling. We conclude that both antibodies,
      despite several common sites labelling, display quite different immunological
      properties, and that the expression "HNK-1" positive has no absolute
      significance.

PMID- 8982641
TI  - Changes in thyroid activity during the annual sexual cycle of a wild avian
      species, the tree pie Dendrocitta vagabunda.
AB  - Thyroid activity was studied during the annual gonadal cycle in both sexes of the
      tree pie (Dendrocitta vagabunda). The study was conducted once a month throughout
      the year by evaluating thyroid weight, epithelial height and peroxidase activity.
      The values of these parameters moderately increased during the progressive phase,
      maximally increased during breeding, decreased in the regression phase and
      decreased further during the non-breeding phase in both sexes of birds. The
      findings indicate that thyroid activity, probably including thyroxine synthesis,
      varies annually, being highest during breeding compared to other phases of the
      gonadal cycle and that, there may be a progonadal relationship of the thyroid
      gland in both sexes of the tree pie.

PMID- 8982640
TI  - Ultrastructural study of the Pacinian corpuscles in the newborn and adult dog
      forefoot.
AB  - Pacinian corpuscles (PC) of the newborn and adult dog forefoot were studied by
      electron microscopy. The PC of newborn dog forefoot show a rare development: they
      exhibit a lamellar arrangement, although the lamellar compartments do not
      surround completely the fiber. The outer core cells show a well-developed
      perinuclear endoplasmic reticulum. They are surrounded by a discontinuous basal
      lamina. Mast cells between the lamellae of the outer core are observed. Desmosome
      like and zonula adherens junctions, as well as pinocytotic vesicles, are shown in
      the inner core cells. Intermediate filaments are also observed in the glial cells
      of the inner core. In PC of adult dog forefoot a general organization of a
      concentrically arranged capsule, outer core, intermediate layer and inner core
      around a nerve ending is always present. In the intermediate layer, lamellar
      cells (specialized fibroblast) do not surround completely the inner core. The
      inner core lamellae possess numerous pinocytotic vesicles, an extensive network
      of filaments, special cell junctions (gap, desmosome) and a discontinuous basal
      lamina. The present results show a conservative structural organization in PC,
      although differences among species are discussed.

PMID- 8982642
TI  - Effects of interdose interval on ambulatory sensitization to methamphetamine,
      cocaine and morphine in mice.
AB  - To determine the minimum interdose interval for induction of ambulatory
      sensitization to methamphetamine, cocaine and morphine, 3 sets of 5 groups of
      mice were treated with either methamphetamine (2 mg/kg s.c.), cocaine (10 mg/kg
      s.c.) or morphine (10 mg/kg s.c.) 3 times at intervals of 3, 6, 12, 24 or 48 h,
      and then 2 times at intervals of 3 days in all groups. During the first 3
      administrations of both methamphetamine and cocaine, interdose intervals of 3-12
      h did not produce a significant change in the ambulatory stimulation. However, 3
      repeated administrations of morphine with interdose intervals of 3 and 6 h, but
      not 12 h, caused tolerance to the ambulatory stimulant effect. The administration
      of all drugs with interdose intervals of 24 and 48 h produced ambulatory
      sensitization. Furthermore, following the fourth and fifth administrations of
      each drug, all groups of mice demonstrated sensitization. These results indicate
      that an interdose interval of 24 h or longer is required for induction of
      ambulatory sensitization to methamphetamine, cocaine and morphine.

PMID- 8982643
TI  - Diltiazem inhibits naloxone-precipitated and spontaneous morphine withdrawal in
      rats.
AB  - The effects of diltiazem, a Ca2+ channel blocker, on naloxone-precipitated and
      spontaneous morphine withdrawal were studied in male Sprague-Dawley rats. In
      naloxone-precipitated withdrawal, body weight loss and plasma corticosterone
      elevation were dose dependently inhibited by diltiazem injected 4 or 2 and 4 h
      before naloxone, respectively. Three administrations of diltiazem (17, 11 and 5 h
      before naloxone) did not reduce the above withdrawal signs. Diarrhea was dose
      dependently inhibited by all schedule of diltiazem treatments. In spontaneous
      withdrawal, body weight loss and plasma corticosterone elevation were dose
      dependently inhibited by two (6 and 12 h) or three (6, 12 and 18 h after the last
      morphine) treatments with diltiazem at 6-h intervals after the last morphine, but
      not by a single diltiazem injected 18 h after the last morphine.

PMID- 8982644
TI  - Effects of peripheral 5-HT2 and 5-HT3 receptor agonists on food intake in food
      deprived and 2-deoxy-D-glucose-treated rats.
AB  - Peripherally administered, the 5-HT2 receptor agonist, alpha-methyl-5
      hydroxytryptamine (alpha-methyl-5-HT), significantly suppressed the food intake
      of food-deprived rats. alpha-Methyl-5-HT also inhibited 2-deoxy-D-glucose-induced
      hyperphagia in rats. The alpha-methyl-5-HT-induced hypophagia was antagonized by
      the 5-HT2A receptor antagonist, ketanserin. The alpha-methyl-5-HT-induced
      decrease in food intake of food-deprived rats was not inhibited by prior
      adrenodemedullation. The peripheral 5-HT3 receptor agonist, 2-methyl-5-HT, did
      not affect food intake in food-deprived or 2-deoxy-D-glucose-treated rats. These
      results suggest that the peripheral 5-HT2A receptor may participate in the
      regulation of food intake and that its hypophagic effects are not associated with
      its adrenaline-releasing effects from the adrenal gland. Lastly, the peripheral 5
      HT3 receptor did not participate in feeding control.

PMID- 8982645
TI  - Effects of a nitric oxide synthase inhibitor on 5-HT1A receptor agonist 8-OH-DPAT
      induced hyperphagia in rats.
AB  - We investigated nitric oxide (NO) involvement in the hyperphagia induced by the 5
      HT1A receptor agonist 8-hydroxy-2-di-n-(propylamino)tetralin (8-OH-DPAT). A NO
      synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), dose dependently
      inhibited 8-OH-DPAT-induced eating in freely feeding rats. However, the inactive
      isomer D-NAME was without effect. The inhibitory effects of L-NAME on 8-OH-DPAT
      induced hyperphagia were reversed by simultaneous administration of L-arginine.
      These results suggest that NO participates in the 8-OH-DPAT-induced hyperphagia
      which is elicited by activation of the 5-HT1A receptor.

PMID- 8982646
TI  - Interactions of agonists with an allosteric antagonist at muscarinic
      acetylcholine M2 receptors.
AB  - The interaction of heptane-1,7-bis(dimethyl-3'-phthalimidopropylammonium bromide)
      (C7/3'-phth), with several agonists, was investigated at the muscarinic M2
      receptor in guinea-pig left atria. C7/3'-phth shifted concentration-response
      curves for the agonists, carbachol, oxotremorine-M and (+)-cis-dioxolane, to the
      right in a parallel fashion. Arunlakshana-Schild regressions of the data yielded
      slopes significantly different to unity, suggesting non-competitive antagonism.
      Non-linear regression analysis, using an equation based on allosteric modulation,
      gave quantitative estimates of co-operativity (alpha values) and the dissociation
      constant of C7/3'-phth (KB). In all cases, the KB estimates for C7/3'-phth were
      not significantly different. Increasing the carbachol contact time 10-fold did
      not significantly influence the KB or the alpha value obtained with C7/3'-phth.
      Changing from Krebs to Tyrode solution did not significantly alter the KB for
      C7/3'-phth, although alpha values obtained were consistently lower in Tyrode
      solution, suggesting that the allosteric action may be sensitive to buffer
      composition. A 4-fold higher degree of negative, heterotropic co-operativity
      between C7/3'-phth and agonists than between C7/3'-phth and competitive
      antagonists was also found.

PMID- 8982647
TI  - Analgesic effects of Tyr-W-MIF-1: a mixed mu2-opioid receptor agonist/mu1-opioid
      receptor antagonist.
AB  - Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) is a naturally occurring neuropeptide that
      displays high selectivity for mu-opioid receptors. Recently, intrathecal (i.t.)
      Tyr-W-MIF-1 was shown to induce potent analgesia mediated through spinal mu2
      opioid receptors in mice. In the current study, we investigated the supraspinal
      analgesic effects of Tyr-W-MIF-1 using intracerebroventricular (i.c.v.)
      administration in mice. I.c.v. Tyr-W-MIF-1 induced a dose-dependent analgesic
      response with an ED50 of 31.4 micrograms that was antagonized by i.c.v. naloxone
      (ED50 = 4.46 nmol) and the mu-opioid receptor antagonist beta-funaltrexamine but
      not by the mu1-opioid receptor-selective antagonist naloxonazine. I.t. naloxone
      (ED50 = 0.12 nmol), however, was nearly 40-fold more potent than i.c.v. naloxone
      at antagonizing i.c.v. Tyr-W-MIF-1-induced analgesia. Tyr-W-MIF-1 also possesses
      antagonist activity at mu1-opioid receptors in brain. Coadministration of i.c.v.
      Tyr-W-MIF-1 with i.c.v. morphine or i.c.v. [D-Ala2, MePhe4, Gly(ol)5]enkephalin
      (DAMGO) significantly decreased the analgesic response to either drug
      administered alone. Thus, Tyr-W-MIF-1 functions as a mixed mu2-opioid receptor
      agonist/mu1-opioid receptor antagonist after i.c.v. administration in mice.

PMID- 8982648
TI  - Effect of maternal delta 9-tetrahydrocannabinol on developing serotonergic
      system.
AB  - In this study we investigated the effects of maternal delta 9
      tetrahydrocannabinol on the developing serotonergic system. A daily dose of delta
      9-tetrahydrocannabinol (5 mg/kg body weight) was administered p.o. to pregnant
      rats from gestational day 5 to postnatal day 1. Levels of indolamines were
      measured in four brain areas of the offspring on the day before or after birth.
      Levels of indolamines depended on the cerebral area, sex and pre- or postnatal
      age. Maternal exposure to delta 9-tetrahydrocannabinol decreased diencephalic
      levels of 5-hydroxytryptamine (5-HT), males being more susceptible than females.
      These perinatal changes could be responsible for the long-term neurophysiological
      alterations produced by cannabinoids.

PMID- 8982649
TI  - Raphe 5-HT1A autoreceptors, but not postsynaptic 5-HT1A receptors or beta
      adrenoceptors, restrain the citalopram-induced increase in extracellular 5
      hydroxytryptamine in vivo.
AB  - In vivo microdialysis in rat ventral hippocampus was used (i) to verify the
      importance of 5-HT1A autoreceptors in the raphe as targets for drugs that enhance
      the citalopram-induced elevation of forebrain 5-hydroxytryptamine (5-HT), and
      (ii) to further examine the specificity of (-)-penbutolol in this regard. The
      selective 5-HT1A receptor antagonist WAY100635 (s.c., or intra-raphe) or the
      mixed 5-HT1A/1B/beta-adrenoceptor antagonist (-)-penbutolol (s.c.), potentiated
      the citalopram-induced 5-HT rise, whereas local "reverse' dialysis of WAY100635
      into the ventral hippocampus did not. Furthermore, the (-)-penbutolol-induced
      augmentation proved stereoselective and not mediated by beta-adrenoceptors (no
      effect of s.c. (+)-penbutolol, or beta 1- and beta 2-adrenoceptor blockers
      (betaxolol, ICI118.551)). These data provide direct evidence that increased
      stimulation of 5-HT1A autoreceptors in the midbrain raphe impedes the effect of
      citalopram on forebrain extracellular 5-HT, whereas neither postsynaptic 5-HT1A
      receptors nor beta-adrenoceptors appear to be involved.

PMID- 8982650
TI  - Effect of chronic moderate ethanol consumption on heart brain natriuretic
      peptide.
AB  - There is experimental evidence indicating that chronic moderate ethanol
      consumption delays the age-dependent increase in blood pressure. Since the brain
      natriuretic peptide (BNP) is a potent hypotensive hormone, the effect of chronic
      ethanol treatment on the heart BNP system was investigated, using spontaneously
      hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Chronic moderate ethanol
      consumption resulted in significantly lower circulating BNP levels for both SHR
      (206.9 +/- 18.5 vs. 306.9 +/- 28.1 pg/ml, n = 12, P < or = 0.05) and WKY rats
      (131.3 +/- 20.7 vs. 220.6 +/- 25.0 pg/ml, n = 12, P < or = 0.05). Left and right
      atrial BNP content and concentration in WKY rats and left atrial BNP content and
      concentration in SHR rats were augmented by the ethanol treatment, but not atrial
      BNP mRNA. In ventricular tissue, alcohol had no effect on total BNP content of
      either SHR or WKY rats, but it induced a significant elevation in ventricular BNP
      concentration (microgram/mg protein) and BNP mRNA in SHR, but not WKY rats. Thus,
      chronic ethanol treatment resulted in specific alterations in the activity of the
      heart BNP system.

PMID- 8982651
TI  - Neuropeptide Y potentiates noradrenaline-induced contraction through the
      neuropeptide Y Y1 receptor.
AB  - To elucidate which neuropeptide Y receptor subtype is responsible for the
      neuropeptide Y-induced potentiation of the noradrenaline-evoked contraction in
      human omental arteries we used antisense oligodeoxynucleotide (Antisense), the
      new selective neuropeptide Y Y1 receptor antagonist, BIBP3226 {(R)-N2
      (diphenylacetyl)-N-[(4-hydroxyphenyl) methyl]-D-arginine-amide} and the reverse
      transcriptase-polymerase chain reaction (RT-PCR). Neuropeptide Y significantly
      potentiated the noradrenaline-induced contraction in non-incubated vessels (pEC50
      6.4 +/- 0.2 vs. 5.9 +/- 0.2) and in vessels incubated with 1 microM Sense
      oligodeoxynucleotide (Sense) (pEC50 6.0 +/- 0.1 vs. 5.6 +/- 0.2). In vessels
      incubated with 1 microM Antisense the potentiating effect of neuropeptide Y was
      completely abolished. BIBP3226 (1 microM) inhibited the neuropeptide Y-induced
      potentiation in human omental arteries (pEC50 5.8 +/- 0.3 vs. 6.4 +/- 0.2).
      Finally, messenger RNA for the neuropeptide Y Y1 receptor was detected using RT
      PCR. On the basis of our results we conclude that the neuropeptide Y-induced
      potentiation of the noradrenaline-induced contraction is mediated by the
      neuropeptide Y Y1 receptor.

PMID- 8982652
TI  - Effects of flurbiprofen and flurbinitroxybutylester on prostaglandin endoperoxide
      synthases.
AB  - The aim of our study was to evaluate the selectivity of flurbiprofen and
      flurbinitroxybutylester for inhibition of the cyclooxygenase activity of
      prostaglandin endoperoxide synthase-2 vs. prostaglandin endoperoxide synthase-1
      in human blood monocytes and platelets, respectively. In whole blood,
      flurbiprofen was approximately 10-fold more potent that flurbinitroxybutylester
      to inhibit the cyclooxygenase activity of platelet prostaglandin endoperoxide
      synthase-1 (IC50 microM: 0.90 +/- 0.27 vs. 10.70 +/- 5, mean +/- S.D., P < 0.05).
      In contrast, the 2 compounds were equipotent to inhibit prostaglandin
      endoperoxide synthase-2 cyclooxygenase activity in whole blood (IC50 microM: 0.90
      +/- 0.25 vs. 0.80 +/- 0.35) or isolated monocytes (IC50 microM: 0.03 +/- 0.02).
      Neither flurbiprofen nor flubinitroxybutylester (0.28-112 microM) affected
      prostaglandin endoperoxide synthase isozyme expression by lypopolysaccharide
      stimulated monocytes. In whole blood, flurbinitroxybutylester was slowly
      converted to flubiprofen and this in turn could influence the extent of
      inhibition of the cyclooxygenase activity of prostaglandin endoperoxide synthase
      1. In conclusion, the addition of a nitroxybutyl moiety to flurbiprofen seems to
      reduce its capacity to inhibit the cyclooxygenase activity of prostaglandin
      endoperoxide synthase-1. Whether this effect will result in a reduced risk of
      gastrointestinal toxicity remains to be studied in man.

PMID- 8982653
TI  - Effect of DP-1904, a thromboxane A2 synthase inhibitor, on passive Heymann
      nephritis in rats.
AB  - The antinephritic effect of DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8
      tetrahydronaphthalene-2-carboxylic acid hydrochloride], a thromboxane A2 synthase
      inhibitor, was evaluated using an experimental model of membranous nephropathy,
      viz. accelerated passive Heymann nephritis in which the glomerular injury is
      mediated by immune complexes. DP-1904 markedly inhibited the develop-ent of
      glomerular alteration as well as the elevation of proteinuria and plasma
      creatinine. When the treatment was started from the 22nd day, at which time
      proteinuria is fully developed, DP-1904 showed beneficial effects on proteinuria
      and glomerular histopathological changes. DP-1904 apparently decreased the
      deposition of both rabbit immunoglobulin G and rat immunoglobulin G on glomerular
      basement membrane in nephritic rats. A single administration of DP-1904 restored
      the decreased renal tissue blood flow, inhibited glomerular thromboxane B2
      production and increased glomerular prostaglandin E2 and 6-keto prostaglandin F1
      alpha production in nephritic rats. These results suggest that DP-1904 may be an
      effective agent for the treatment of idiopathic membranous nephropathy and that
      the beneficial effect of this drug may be due to the elimination of glomerular
      immune deposits and to an increase in renal tissue blood flow related to
      amelioration of the abnormal metabolism of arachidonic acid.

PMID- 8982655
TI  - The local anesthetic, n-butyl-p-aminobenzoate, reduces rat sensory neuron
      excitability by differential actions on fast and slow Na+ current components.
AB  - Effects of the local anesthetic, n-butyl-p-aminobenzoate, at a concentration of
      100 microM, were investigated using the whole-cell voltage clamp on dorsal root
      ganglion neurons cultured from neonatal rat in a serum-enriched medium. During
      current clamp conditions, the drug either increased the firing threshold or
      blocked tetrodotoxin-sensitive and tetrodotoxin-resistant Na+ action potentials.
      These actions were reversible. Under voltage clamp conditions, inactivation of
      the Na+ current revealed the existence of 3 fast Na+ current components, termed
      F1, F2 and F3 (tetrodotoxin-sensitive) and 2 slow ones, termed S1 and S2
      (tetrodotoxin-resistant). The local anesthetic shifted the midpoint potentials of
      Na+ inactivation curves for F1, F2 and F3 currents by 7, 21 and 6 mV,
      respectively, towards hyperpolarizing membrane voltages whereas it did not
      influence these potentials for the slow currents. The amplitudes of only F3 and
      S2 currents were reduced by n-butyl-p-aminobenzoate to 24 and 11%, respectively,
      of their control values. These results show that the local anesthetic has a
      differential mode of action on the 5 types of Na+ currents, which are apparently
      present in cultured sensory neurons. This differential action can play an
      important role in the selective analgesic effect observed after epidural
      administration of a 10% n-butyl-p-amino-benzoate suspension.

PMID- 8982654
TI  - Stimulation of formation of adenosine 3',5'-phosphate by histamine in myenteric
      ganglia isolated from guinea-pig small intestine.
AB  - Effects of histamine and related agonists and antagonists on formation of cAMP
      were determined for enzymatically dissociated ganglia from the myenteric plexus
      of the guinea-pig small intestine. Formation of cAMP was stimulated by histamine
      in both dose- and time-dependent manners. The stimulatory action of histamine was
      suppressed by the histamine H2 receptor antagonist, cimetidine. The histamine H1
      receptor antagonists, tripelennamine or pyrilamine also suppressed the
      stimulatory action of histamine, but only at concentrations 3-4 orders higher
      than required for cimetidine. Formation of cAMP was stimulated dose-dependently
      by the histamine H2 receptor agonist, dimaprit. The histamine H1 receptor
      agonist, 2-methyl-histamine, also stimulated cAMP production, but required a
      threshold concentration 4-5 orders higher than dimaprit. We conclude that
      histamine acts at the histamine H2 receptor subtype to stimulate adenylate
      cyclase and the formation of cAMP in myenteric ganglia of the guinea-pig small
      bowel.

PMID- 8982656
TI  - Na+/Ca2+ exchange current: lack of effect of taurine.
AB  - The intracellular taurine content is very high in some types of cells, including
      myocardial cells, and taurine becomes depleted in failing hearts. The effect of
      taurine on inward (forward) and outward (reversal) Na+/Ca2+ exchange current
      (INa/Ca) was examined in freshly isolated rat (11-20-day-old) ventricular cells
      using whole-cell voltage clamp. INa/Ca was evoked by a 300 ms ramp
      hyperpolarizing pulse at a rate of 0.67 V/s (from +60 to -140 mV) from a holding
      potential of -40 mV. Under the condition of 500 nM Ca2+ in the pipette, when the
      bath solution was changed from 150 mM Li+ to 150 mM Na+, an inward INa/Ca was
      initiated. On the other hand, under the condition of 50 mM Na+ and 56 nM Ca2+ in
      the pipette, when the bath solution was changed from Na(+)-free, Ca(2+)-free
      solution to Na(+)-free, 2 mM Ca2+, an outward INa/Ca was initiated. Both inward
      and outward INa/Ca were completely blocked by 5 mM Ni2+, helping to identify the
      current as INa/Ca. Forward and reversal INa/Ca was measured in the absence
      (control) and presence of 30 mM taurine added to the bath. The current densities
      (pA/pF) of inward INa/Ca at -50 mV were 0.75 +/- 0.12 in control and 0.73 +/-
      0.11 in presence of 30 mM taurine. Outward INa/Ca at +50 mV were 0.73 +/- 0.08 in
      control and 0.65 +/- 0.02 in 30 mM taurine. There were no significant differences
      between control and taurine for both inward and outward INa/Ca. Therefore, the
      various effects of taurine reported on the heart are not caused by a direct
      effect of taurine on Na/Ca exchange.

PMID- 8982657
TI  - Direct evidence for two distinct G proteins coupling with thrombin receptors in
      human neuroblastoma SH-EP cells.
AB  - Thrombin receptor-G protein coupling was investigated in the human epithelial
      neuroblastoma cell line, SH-EP. In these cells, both alpha-thrombin and thrombin
      receptor peptides, SFLLRNP (one-letter amino-acid code), which are newly exposed
      following cleavage by alpha-thrombin, stimulated GTPase activity about 2-fold
      over basal activity. Pertussis toxin treatment only partially attenuated alpha
      thrombin- and SFLLRNP-stimulated GTPase activity by 50%, whereas antibody raised
      against synthetic heptapeptide SFLLRNP blocked alpha-thrombin-stimulated
      phosphoinositide hydrolysis more than 80%. Immunoprecipitation studies using this
      antibody showed that both Gi2, a subtype of guanine nucleotide-binding regulatory
      proteins (G proteins) mediating inhibition of adenylyl cyclase, and Gq/G11, a G
      protein mediating stimulation of phospholipase C, were activated by alpha
      thrombin. These data suggest that in these cells the thrombin receptor activates
      pertussis toxin-sensitive and pertussis toxin-insensitive G proteins
      simultaneously and directly couples to Gi2 and Gq/G11, which mediate different
      signaling pathways.

PMID- 8982658
TI  - Probing human beta 1- and beta 2-adrenoceptors with domain-specific fusion
      protein antibodies.
AB  - In order to generate antibodies suitable for immunological studies on beta
      adrenoceptors constitutively expressed at low levels in cells or tissues we have
      produced fusion proteins of the amino- and carboxy-terminus, and the second
      extracellular loop of the human beta 1- or beta 2-adrenoceptors with bacterial
      glutathione-S-transferase in E. coli. Rabbit antibodies raised against these
      fusion proteins strongly reacted with intact human beta 1- or beta 2
      adrenoceptors in a subtype- and domain-specific manner. Antibodies directed
      against the second extracellular loop of the beta 1-adrenoceptor reacted stronger
      with non-denatured receptors and decreased the affinity of the 3H-labelled
      antagonist (-)-4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one
      ([3H]CGP 12 177), indicating a specific interaction with the native receptor. In
      contrast, antibodies directed against carboxy- and amino-terminal receptor
      domains reacted strongly both with denatured and non-denatured receptors but did
      not interfere with binding of [3H]CGP 12 177. Affinity purified antibodies were
      used for detecting the beta 1- or the beta 2-adrenoceptor subtype heterologously
      produced in Sf9 cells by enzyme-linked immunosorbent assay, Western blotting,
      immunoprecipitation, and indirect immunofluorescence microscopy. Moreover, we
      could demonstrate that avidity, titers, and specificity of these antibodies were
      high enough for studying beta-adrenoceptors constitutively expressed in human
      A431 cells, where we observed a patched membrane distribution of the receptors.

PMID- 8982659
TI  - Influence of nitric oxide on transepithelial transport in toad skin: effects of
      cholinergic agents and morphine.
AB  - The effects induced by L-arginine (L-Arg) on the short-circuit current and
      potential difference of Pleurodema thaul skin were investigated. L-Arg, but not D
      Arg significantly increased the short-circuit current and potential difference
      when applied to the serosal surface. The effects of L-Arg were antagonized by
      amiloride, NG-nitro-methyl-L-arginine (L-NAME) and by methylene blue. Carbachol
      and acetylcholine induced significant increases of both electrical parameters of
      the toad skin. These effects of the muscarinic cholinergic drugs were potentiated
      by a low concentration of L-Arg and antagonized by L-NAME or methylene blue.
      Carbachol and acetylcholine induced significant increases of both electrical
      parameters of the toad skin. These effects of the muscarinic cholinergic drugs
      were potentiated by a low concentration of L-Arg and antagonized by L-NAME or
      methylene blue. Addition of dibutyryl cyclic guanosyl monophosphate (db cGMP) or
      dibutyryl cyclic adenosine monophosphate (db cAMP) increased short-circuit
      current and potential difference. The effects of db cGMP, but not those of db
      cAMP were antagonized by L-NAME. The consecutive application of db cGMP and db
      cAMP induced additive effects. These results suggest that L-Arg increases
      transport in toad skin presumably acting through the formation of nitric oxide,
      which then stimulates cytoplasmic guanylate cyclase and leads to increased Na+
      and K+ transport. The effects of L-Arg and carbachol were antagonized by acute
      application of morphine; however, a rebound response was observed when carbachol
      or noradrenaline were given after prolonged exposure of the skin to morphine,
      which suggests an adaptive response of the skin involving both cGMP and cAMP.
      Responses to both nucleotides were unchanged by morphine.

PMID- 8982660
TI  - Neuropharmacological profile of EMD 57445, a sigma receptor ligand with potential
      antipsychotic activity.
AB  - EMD 57445 ((S)-(-)-[4-hydroxy-4-(3,4-benzodioxol-5-yl) -piperidin-1-ylmethyl]-3
      (4-methoxyphenyl)-oxazolidin- 2-one) is a new sigma receptor ligand with only
      marginal affinity for many other (including dopamine) receptors. In the present
      study, central, particularly neuroleptic-like, effects of this compound were
      evaluated and compared with those of another sigma receptor ligand, rimcazole.
      EMD 57445 decreased locomotor activity in rats and mice. The amphetamine-induced
      locomotor hyperactivity and stereotypy were reduced by EMD 57445. The drug was
      able to inhibit the behavioural effects induced by apomorphine, i.e., the
      locomotor hyperactivity, stereotypy and aggression in rats, as well as climbing
      in mice. The hyperlocomotion induced by quinpirole (a dopamine D2/3 receptor
      agonist) and the grooming induced by SKF 38393 (a dopamine D1 receptor agonist)
      were decreased by EMD 57445. The behavioural stimulation evoked in rats by non
      competitive (MK-801, (+)-5-methyl-10,11-dihydroxy-5H-dibenzo (a,b)-cyclohepten
      5,10-imine hydrogen maleate) or competitive (CGP 37849, D,L-E-amino-4-methyl-5
      phosphono-3-pentenoic acid) NMDA receptor antagonists was also inhibited. EMD
      57445 decreased the cocaine-, morphine- or caffeine-induced locomotor
      hyperactivity in rats or mice. It neither induced catalepsy nor increased muscle
      tone in rats. Rimcazole had somewhat different effects: it increased the
      amphetamine stereotypy as well as the amphetamine-, quinpirole- and cocaine
      induced locomotor hyperactivity in rats. The results indicate that EMD 57445
      shows functional antidopaminergic activity and may be useful as an antipsychotic
      drug devoid of extrapyramidal side-effects.

PMID- 8982661
TI  - Assessment of relative efficacies of 5-HT1A receptor ligands by means of in vivo
      animal models.
AB  - We have evaluated the effects of ligands with varying efficacies at beta
      adrenoceptors and 5-HT1A receptors in three in vivo models reflecting pre- and/or
      postsynaptic 5-HT1A receptor activation. Forepaw treading in rats is mediated by
      postsynaptic 5-HT1A receptors, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamin)tetralin)
      induced discriminative stimulus is predominantly mediated by postsynaptic, but
      presynaptic 5-HT1A receptors might also be involved, and footshock-induced
      ultrasonic vocalization involves predominantly presynaptic 5-HT1A receptors. In
      vitro receptor binding studies demonstrated high beta-adrenoceptor and 5-HT1A
      receptor affinity of (-)-penbutolol, high beta-adrenoceptor and 60 times lower 5
      HT1A receptor affinity of (+)-penbutolol, high beta-adrenoceptor affinity and
      about 100 times lower 5-HT1A receptor affinity of pindolol and (-)-tertatolol,
      only affinity for beta-adrenoceptors of metoprolol and ICI 118,551 (erythro-D,L-1
      (7-methylindan-4-yloxy)-3-isopropylamine-b utan-2-ol, and only affinity for 5
      HT1A receptors of WAY 100.635 ((N-[2-[4- (2-methoxyphenyl)-1-piperazinyl]ethyl]-N
      (2-pyridinyl) cyclo-hexane-carboxamide). (-)-Penbutolol, (-)-tertatolol, pindolol
      and WAY 100.635 antagonized 5-MeODMT-induced (5-methoxy-N, N-dimethyltryptamine)
      forepaw treading in rats, and (+)-penbutolol, ICI 118,551 and metoprolol were
      inactive. (-)-Penbutolol, WAY 100.635 and (-)-tertatolol antagonized 8-OH-DPAT
      induced discriminative stimulus in rats, pindolol and metoprolol showed a mixed
      antagonistic and agonistic profile. Pindolol antagonized footshock-induced
      ultrasonic vocalization in rats, tertatolol inhibited maximum 36% and WAY
      100.635, (-)-penbutolol, (+)-penbutolol, metroprolol and ICI 118,551 were
      inactive. (-)-Penbutolol and WAY 100.635 reversed 8-OH-DPAT-induced inhibition of
      ultrasonic vocalization completely, (-)-tertatolol reversed maximum 52% and (+)
      penbutolol and pindolol were inactive. It is concluded, that efficacies at 5-HT1A
      receptors can be estimated by applying a battery of in vivo test models that
      involve post- and presynaptic receptors to a variable degree. The in vivo ranking
      order of efficacy at 5-HT1A receptors was: WAY 100.635 = (-)-penbutolol < (-)
      tertatolol < pindolol.

PMID- 8982662
TI  - Pharmacological characterization of P2 purinoceptor types in rat locus coeruleus
      neurons.
AB  - The frequency of spontaneous action potentials of locus coeruleus neurons was
      recorded extracellularly in pontine slices of the rat brain. The adenosine 5'
      triphosphate (ATP) analogues alpha,beta-methylene ATP (alpha,beta-meATP) and 2
      methylthio ATP increased the firing rate with a similar potency, while uridine 5'
      triphosphate (UTP) was inactive. Diadenosine 5'-pentaphosphate (Ap5A),
      diadenosine 5'-tetraphosphate (Ap4A) and diadenosine 5'-triphosphate (Ap3A) all
      facilitated the firing. When equimolar concentrations were compared, Ap5A had the
      largest effect followed by Ap4A and Ap3A. Suramin markedly inhibited responses to
      alpha,beta-meATP and 2-methylthio ATP; the effect of Ap4A was only slightly
      depressed by suramin. Pyridoxalphosphate-6-azophenyl-2,4-disulfonic acid (PPADS)
      strongly antagonized alpha, beta-meATP, but failed to alter the effects of 2
      methylthio ATP and Ap4A. Reactive blue 2 weakly antagonized alpha,beta-meATP and
      did not interfere with 2-methylthio ATP and Ap4A. Moreover, suramin depressed
      responses to (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      and N-methyl-D-aspartic acid (NMDA), but not to substance P. PPADS failed to
      affect the AMPA- and NMDA-induced increases in firing. Hence, locus coeruleus
      neurons may possess receptors for adenosine nucleotides (P2X and P2Y
      purinoceptors) and dinucleotides (P2D purinoceptors); receptors for uridine
      nucleotides (P2U purinoceptors or pyrimidinoceptors) are probably absent.

PMID- 8982663
TI  - (R,S)-3,4-dichlorobenzoylalanine (FCE 28833A) causes a large and persistent
      increase in brain kynurenic acid levels in rats.
AB  - Kynurenic acid is an endogenous excitatory amino-acid receptor antagonist with
      neuroprotective and anticonvulsant properties. We demonstrate here that systemic
      administration of the new and potent kynurenine 3-hydroxylase inhibitor (R,S)-3,4
      dichlorobenzoylalanine (FCE 28833A) causes a dose-dependent elevation in
      endogenous kynurenine and kynurenic acid levels in rat brain tissue. In
      hippocampal microdialysates, peak increases of 10- and 80-fold above basal
      kynurenic acid concentrations, respectively, were obtained after a single oral or
      intraperitoneal administration of 400 mg/kg FCE 28833A. After intraperitoneal
      treatment with FCE 28833A, extracellular brain kynurenic acid levels remained
      significantly elevated for at least 22 h, rendering this compound a far more
      effective enhancer of kynurenic acid levels than the previously described
      kynurenine 3-hydroxylase blocker m-nitrobenzoylalanine. FCE 28833A and similar
      molecules may have therapeutic value in diseases which are linked to a
      hyperfunction of excitatory amino-acid receptors.

PMID- 8982664
TI  - Lack of cross-tolerance between haloperidol and clozapine towards Fos-protein
      induction in rat forebrain regions.
AB  - We investigated whether the acute effects of haloperidol and clozapine on Fos
      expression in the rat forebrain are mediated by the same receptors through
      evaluation of cross-tolerance, particularly in the commonly affected areas.
      Acutely administered haloperidol (1 mg/kg. i.p.) and clozapine (20 mg/kg, i.p.)
      induce regionally different (e.g., the striatum, the hypothalamic paraventricular
      and supraoptic nuclei, and the central amygdala) and overlapping (e.g., the
      nucleus accumbens and the lateral septum) patterns of Fos-protein distribution in
      the rat forebrain. After long-term treatment, part of the acute effects of these
      drugs disappears in most brain areas, except in the lateral septum, the
      hypothalamic paraventricular and supraoptic nuclei and the amygdala following
      haloperidol administration. Cross-tolerance between haloperidol and clozapine was
      determined by administering a challenge dose of the one antipsychotic, following
      a 21-day pretreatment with the same or the other drug or saline. In none of the
      investigated brain regions was cross-tolerance towards Fos-protein induction
      found after haloperidol challenge in the clozapine-treated rats. Conversely, a
      competitive dose of clozapine in long-term haloperidol-treated rats showed cross
      tolerance in the lateral septum, while the common effect of the drugs in both the
      dorsomedial and the dorsolateral parts of the striatum was very small. These
      findings indicate that, for the major part, the responses to haloperidol and
      clozapine are mediated by different receptors, even in brain areas that are
      affected by both drugs.

PMID- 8982665
TI  - Effect of prior ethanol experience on dopamine overflow in accumbens of AA and
      ANA rats.
AB  - The purpose of this study was to investigate the effect of repeated ethanol
      administration on dopamine overflow in the nucleus accumbens of alcohol
      preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko Nonalcohol) rats.
      Dopamine is a possible mediator of the reinforcing effects of ethanol, but it has
      previously been shown that ethanol-naive alcohol-preferring AA and alcohol
      nonpreferring ANA rats do not differ in their dopaminergic reaction to an
      intraperitoneal ethanol injection (0.5-2.0 g/kg), as assessed by measuring
      extracellular dopamine in the nucleus accumbens with in vivo microdialysis. Here
      a group of AA rats drank 10% (v/v) ethanol voluntarily-continual access for 5-15
      days, limited access for 3 weeks-while a yoked group of AA rats and a yoked group
      of ANA rats received the same amount intragastrically by intubation. The rats
      were implanted with guide cannulas on the fourth week of limited access. Dopamine
      overflow was monitored in the microdialysis perfusate after 1 g/kg i.p. ethanol.
      The AA and the ANA rats that received ethanol non-contingently showed the same
      dopaminergic response to this as naive animals have before. The group that had
      ingested the ethanol voluntarily showed, however, a significantly smaller
      increase in dopamine after 1 g/kg ethanol i.p. This suggests that the active
      behavior associated with obtaining the contingent drug may have an important
      impact on the reactions of the dopamine system to the drug, producing different
      results than when the same drug is administered by other routes. The hypothesis
      that dopamine mediates ethanol reinforcement in AA rats is not supported by the
      results.

PMID- 8982667
TI  - PACAP-38 activates parasympathetic nerves in isolated, blood-perfused dog atria.
AB  - A pituitary adenylate cyclase-activating polypeptide (PACAP) activates PACAP and
      vasoactive intestinal peptide (VIP) receptors. We investigated the effects of
      PACAP-38 on the sinus rate and atrial contractile force in isolated, blood
      perfused dog heart preparations and the stimulation by PACAP-38 of the
      parasympathetic nerve fibers. PACAP-38 (3-1000 pmol) caused positive and/or
      negative chronotropic responses and it dose dependently increased atrial and
      ventricular contractile force. The positive cardiac responses to PACAP-38 unlike
      those to VIP were much less than the positive responses to norepinephrine.
      Atropine inhibited the negative chronotropic responses to PACAP-38 and augmented
      the positive chronotropic and inotropic responses. Physostigmine potentiated the
      negative cardiac responses to PACAP-38 and acetylcholine. After physostigmine
      treatment, additionally, tetrodotoxin blocked the negative cardiac responses to
      PACAP-38 and intracardiac parasympathetic nerve stimulation. Propranolol did not
      inhibit the positive cardiac responses to PACAP-38 in atropine-treated atria.
      PACAP-(6-38) (1 and 3 nmol), an antagonist of PACAP-38, did not affect the
      cardiac responses to 100 pmol of PACAP-38. These results suggest that (1) PACAP
      38 directly increases sinus rate and atrial contractile force and (2) PACAP-38
      activates parasympathetic nerves and causes negative chronotropic and inotropic
      responses in the dog heart.

PMID- 8982666
TI  - Effects of felbamate on veratridine- and K(+)-stimulated release of glutamate
      from mouse cortex.
AB  - Felbamate is a novel anticonvulsant which may modulate the strychnine-insensitive
      glycine site of the N-methyl-D-aspartate (NMDA) receptor complex. This study
      examined the effect of felbamate and 5,7-dichlorokynurenic acid on veratridine
      (20 microM)- and K+ (60 mM)-stimulated release of amino acids in mouse cortical
      slices. Felbamate significantly decreased veratridine-induced release of
      glutamate at 400 microM and 800 microM but had no effect on K(+)-stimulated
      release. 5,7-Dichlorokynurenic acid had no effect on amino-acid release in
      concentrations up to 200 microM. The inhibitory effect of felbamate on
      veratridine-induced release of glutamate may be due to inactivation of voltage
      sensitive Na+ channels.

PMID- 8982668
TI  - Prevention by the new Ca2+ channel antagonist, AJ-3941, of loss of endothelium
      dependent relaxation after subarachnoid hemorrhage in rats.
AB  - AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11-yl ) -4-(3
      phenyl-2-propenyl)-piperazine dimaleate; CAS No. 143110-70-7), a cerebrovascular
      selective Ca2+ channel antagonist having anti-lipid peroxidative action, was
      reported to prevent cerebral vasospasm following subarachnoid hemorrhage in rats.
      The present study was undertaken to determine whether AJ-3941 protects the
      impairment of cerebroarterial endothelium-dependent relaxation which is
      concomitantly induced with cerebral vasospasm. Subarachnoid hemorrhage
      biphasically suppressed the response to acetylcholine in rat basilar artery, at
      0.5 h (n = 4; P < 0.06) and 1 day (n = 5; P < 0.05) after subarachnoid
      hemorrhage. The reduction of the responses was correlated significantly to the
      degree of vasospasm determined angiographically. This reduction was accompanied
      by a 49% increase of arterial lipid peroxide contents. Endothelium-independent
      relaxation in subarachnoid hemorrhage rats was preserved in response to 3
      morpholinosydnonimine, sodium nitroprusside and papaverine. AJ-3941 prevented (n
      = 6-8, P < 0.05) the suppression of the acetylcholine-induced response and the
      increase in lipid peroxide content in subarachnoid hemorrhage rats. These results
      suggest that AJ-3941 could exert its vasospasmolytic effect by preserving
      endothelial function through its anti-lipid peroxidative action, in addition to
      its inhibition of vasospasmogen-induced vasoconstriction related to intracellular
      Ca2+ mobilization.

PMID- 8982669
TI  - Effect of pentacaine and its derivatives on the contractile responses of smooth
      muscle in the guinea-pig stomach.
AB  - The effect of a carbanilic local anesthetic pentacaine [(+/-)-trans-2- (1
      pyrrolidinyl)cyclohexyl ester of 3(n)-pentyloxyphenyl-carbanilic acid] and some
      of its derivatives [K-1905 [(+/-)-trans-2-diethylaminocyclopentyl ester of 3(n)
      pentyloxyphenyl-carbanilic acid], K-2002 [(+/-)-trans-2-(1
      pyrrolidinyl)cyclohexyl ester of 4(n)-pentyloxyphenyl-carbanilic acid], K-2006
      [(+/-)-trans-2-(1-pyrrolidinyl)cyclopentyl ester of 4(n)-pentyloxyphenyl
      carbanilic acid], and carbanilates P2 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl
      ester of 4-methoxy-carbonylphenyl-carbanilic acid], P3 [(+/-)-trans-2-(1
      pyrrolidinyl)cyclohexyl ester of 3-methoxy-phenyl-carbanilic acid], and PeJ, the
      quaternized derivative of pentacaine), as well as that of oxethazaine was studied
      on longitudinal antral and circular fundic smooth muscle strips of the guinea-pig
      stomach. All the carbanilates studied relaxed the smooth muscle, attenuated the
      spontaneous smooth muscle contractions and shifted the acetylcholine, histamine,
      and BaCl2 cumulative concentration effect curves to the right, reducing their
      maximum. There was no direct relationship between their relaxing potency and the
      ability to reduce the action of different stimulants. For the effectiveness of
      the carbanilates studied, substitution in the lipophilic part of the molecule was
      more important than in the hydrophilic part and the meta position was more
      advantageous than the para position. Pentyloxy-derivatives (pentacaine, K-1905, K
      2002 and K-2006) were more active than the methylcarbonyloxy (P2)- and methoxy
      (P3)-derivatives. Opening of the heterocyclic ring (K-1905) in the hydrophilic
      part of the molecule did not affect significantly the potency of the derivative
      studied, while quaternization (PeJ) significantly reduced the potency. It is
      suggested that the carbanilates studied may affect the smooth muscle responses
      via changes in the membrane fluidity and Ca2+ availability, and that these
      effects might be partly responsible also for their antiulcer activity.

PMID- 8982670
TI  - Halothane counteracts acetylcholine-induced increase in Ca2+ sensitivity of the
      contractile apparatus in airway smooth muscle.
AB  - The direct relaxing effect of halothane on airway smooth muscle has been reported
      to involve the reduction of the cytosolic Ca2+ concentration ([Ca2+]i) and the
      [Ca2+]i-independent inhibitory mechanism. To clarify the extent of the
      contribution of these mechanisms, the effect of halothane on the [Ca2+]i-tension
      relationship in porcine tracheal smooth muscle strips was evaluated, using fura-2
      fluorometry. The control [Ca2+]i-tension relationship was constructed from data
      of [Ca2+]i and tension during the contractions induced by the stepwise increment
      of extracellular Ca2+ concentrations under high K+ depolarization. In the
      presence of acetylcholine (1 microM), the [Ca2+]i-tension relationship shifted
      upward, which indicated the acetylcholine-induced increase in the Ca2+
      sensitivity of the contractile apparatus. Halothane (0.034 mM), in the absence of
      acetylcholine, did not alter the increases in either [Ca2+]i or tension, hence no
      change in the [Ca2+]i-tension relationship. However, in the presence of
      acetylcholine, halothane did attenuate the acetylcholine-induced upward shift of
      the [Ca2+]i-tension relationship. Halothane proved to have a potent attenuating
      effect on the acetylcholine-induced increase in Ca2+ sensitivity of the
      contractile apparatus with little influence on [Ca2+]i. This desensitization of
      the contractile apparatus to [Ca2+]i may play a major role in the direct airway
      relaxing effect of halothane.

PMID- 8982671
TI  - Adrenomedullin-sensitive receptors are preferentially expressed in cultured rat
      mesangial cells.
AB  - By using cultured rat mesangial cells, we compared the effects on cyclic
      nucleotide levels of adrenomedullin with those of the structurally related
      peptides, calcitonin gene-related peptide (CGRP) and amylin. Adrenomedullin
      potently increased cAMP levels 7-fold in a time- and concentration-dependent
      manner. Its EC50 was 3 x 10(-9) M. CGRP was less potent (2-fold) with an EC50 of
      10(-7) M, and amylin had no effect on cAMP levels. All three peptides failed to
      increase cGMP levels. Treatment of cells with near maximal concentrations of
      adrenomedullin (10(-7) M) and CGRP (10(-6) M) had no additive effect on cAMP
      levels. Human adrenomedullin-(22-52)-NH2, a putative adrenomedullin receptor
      antagonist, inhibited the production of cAMP elicited by adrenomedullin (IC50: 7
      x 10(-8) M) and CGRP (IC50: 5 x 10(-8) M). Human CGRP-(8-37), a CGRP receptor
      antagonist, conversely, reduced the cAMP elevation caused by these peptides with
      a lower potency (IC50: 10(-6) M for both peptides). This demonstrated that human
      adrenomedullin-(22-52)-NH2 was a more effective antagonist for adrenomedullin-
      and CGRP-specific receptors than human CGRP-(8-37). Results suggest that
      receptors sensitive to adrenomedullin are preferentially expressed in cultured
      rat mesangial cells. Immunohistochemical study showed almost no immunoreactive
      adrenomedullin and CGRP, if any, in the cells. Adrenomedullin may regulate
      mesangial function as either a paracrine or circulating hormone via a cAMP- but
      not a cGMP-dependent mechanism.

PMID- 8982672
TI  - Receptor and mechanism that mediate endothelin- and big endothelin-1-induced
      phosphoinositide hydrolysis in the rat spinal cord.
AB  - In rat spinal cord slices, endothelin-1 and endothelin-3 enhanced [3H]inositol
      phosphate production between 1 nM and 10 microM (endothelin-1 > endothelin-3)
      while sarafotoxin 6c and the endothelin ETB receptor agonist IRL-1620 (Suc
      [Glu9,Ala11,15]endothelin-1-(8-21)) were almost ineffective. BQ-123 (cyclo(D
      Trp,D-Asp,L-Pro,D-Val,L-Leu), a selective endothelin ETA receptor antagonist,
      reduced the endothelin-1- and endothelin-3-induced [3H]inositol phosphate
      production, with similar inhibition constants (IC50: 16.7 +/- 3.4 and 8.0 +/- 1.6
      microM, respectively). The inhibition of endothelin-1 was enhanced when BQ-123
      was preincubated for 30 min instead of 15 min. BQ-788 (N-cis-2,6
      dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D -1-methoxy-
      carbonyltryptophanyl-D-Nle), a selective ETB receptor antagonist, did not modify
      the endothelin-1-induced [3H]inositol phosphate production. Big endothelin-1 (1
      nM to 1 microM) was slightly less potent than endothelin-1 in enhancing
      [3H]inositol phosphate production. This response was sensitive to phosphoramidon
      and [Phe22]big endothelin-1-(19-37), two inhibitors of endothelin-converting
      enzyme. Pretreatment of slices with pertussis toxin, indomethacin or PN 200-110
      ((-)-isradipine, a dual inhibitor of L- and R-type Ca2+ channels) did not alter
      the response to 1 microM endothelin-1 while this response was abolished by
      tetrodotoxin. Finally, endothelin-1 enhanced [3H]inositol phosphate production
      with an identical EC50 (2.1 nM) in spinal cord slices of Wistar-Kyoto rats (WKY)
      and spontaneously hypertensive rats (SHR) although the maximal response was
      reduced in SHR. These data indicate that endothelins stimulated [3H]inositol
      phosphate production in the rat spinal cord through the activation of an
      endothelin ETA receptor that trigger the release of an unidentified
      neurotransmitter. This effect does not appear to be associated to activation of a
      Gi/G(o)-type of G-protein, dihydropyridine-sensitive L-type Ca2+ channels or to
      the production of prostaglandins. Furthermore, the findings support the presence
      of a phosphoramidon-sensitive endothelin-converting enzyme in the spinal cord.

PMID- 8982673
TI  - Interaction of propranolol with S100 proteins of the cardiac muscle.
AB  - The cardioprotective activity of propranolol is believed to be independent of its
      beta-adrenoceptor antagonistic effect. Propranolol exerts this effect through a
      direct effect on the cardiac muscle, but the precise mechanism remains unclear.
      In this work, we demonstrated that propranolol binds to S100ao and S100L proteins
      with ED50 of approximately 1.0 microM without cation dependency and that this
      binding changes the conformation of these S100 proteins. Propranolol, however,
      was found to bind to and to change the conformation of S100C protein in the
      presence of Mg2+ or Zn2+ with ED50 of approximately 1.0 microM. No change was
      observed in the presence of Ca2+. Moreover, in the presence of Mg2+, the ED50 of
      L- and D- propranolol were approximately 0.8 and 2.0 microM, respectively. This
      study demonstrated for the first time, that the S100 proteins of the cardiac
      muscle are intracellular targets of propranolol, and that Mg2+ is a modulator of
      the cardioprotective activity of S100C protein.

PMID- 8982674
TI  - Competitive inhibition of photoaffinity labelling of P-glycoprotein by anticancer
      drugs and modulators including S9788.
AB  - The affinity of the multidrug resistance modulator S9788 to interact with P
      glycoprotein was characterized by its ability to inhibit the photoaffinity
      labelling of plasma membranes of multidrug resistant chinese hamster ovary B30
      cells by iodomycin. This iodinated analogue of daunomycin specifically
      photolabels P-glycoprotein in membrane vesicles as well as in intact cells. The
      multidrug resistance reversing agents verapamil and cyclosporin and the cytotoxic
      drugs vinblastine and daunomycin which are known to be recognized by P
      glycoprotein competed with iodomycin for its binding site on P-glycoprotein.
      Vinblastine and cyclosporin bound with high affinity, S9788 and verapamil with
      medium affinity to P-glycoprotein.

PMID- 8982675
TI  - Regulation of the functional activity of the human dopamine transporter by the
      arachidonic acid pathway.
AB  - The role of arachidonic acid was examined in the regulation of dopamine transport
      in C6 glioma cells stably expressing the human dopamine transporter. Exogenously
      added arachidonic acid (20-160 microM) stimulated [3H]dopamine uptake when pre
      incubated for short times (15-30 min); 160 microM arachidonic acid inhibited
      following longer pre-exposures (45-60 min). Under the same conditions, only
      decreases were observed in the binding of the cocaine analog [3H]2 beta
      carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]WIN 35,428). The reduction in
      dopamine transporter activity by arachidonic acid (at 160 microM for 60 min) was
      caused by a decrease in the Vmax (from 202 to 44 pmol/mg/min) opposed by a
      smaller reduction in K(m) (from 1.2 to 0.8 microM), whereas the effect of
      arachidonic acid (at 160 microM for 15 min) on [3H]WIN 35,428 binding was caused
      by a reduction in the Bmax (from 1.8 to 1.3 pmol/mg) without a change in Kd (7.2
      nM). Upon 15-min exposure, melittin, an activator of phospholipase A2, and
      nordihydroguaiaretic acid, a lipooxygenase inhibitor, both expected to cause
      enhanced endogenous arachidonic acid, inhibited [3H]dopamine uptake and [3H]WIN
      35,428 binding with an IC50 value close to 1 microM, whereas thimerosal, which
      raises arachidonic acid by inhibiting lipid reacylation, caused similar
      reductions at the sub-millimolar level. Co-presence of stauroporine (0.3-2
      microM), an inhibitor of protein kinase C, had little or no effect on the
      melittin- or arachidonic acid-induced inhibition of [3H]dopamine uptake. Both the
      melittin- and arachidonic acid-, but not phorbol 12-myristate 13-acetate-induced
      inhibition of uptake were counteracted by bovine serum albumin (0.1 and 1 mg/ml)
      which binds arachidonic acid. The data taken together suggest that the inhibitory
      effects of arachidonic acid activators and those of protein kinase C activators
      on dopamine uptake are mediated by separate mechanisms.

PMID- 8982676
TI  - High-affinity binding of [3H]neuropeptide Y to a polypeptide from the venom of
      Conus anemone.
AB  - Venom preparation from Conus anemone contains a component that binds radiolabeled
      neuropeptide Y ([3H]neuropeptide Y) with high affinity (KD = 2.9 nM +/- 0.2 nM,
      Bmax = 15.2 +/- 0.5 pmol/mg protein). Binding of [3H]neuropeptide Y to the venom
      component is displaced with nanomolar affinity of unlabeled human and porcine
      neuropeptide Y, porcine [Leu31-Pro34]neuropeptide Y, peptide YY, avian and bovine
      pancreatic polypeptide, and the (18-36) and (25-36) C-terminal fragments from
      neuropeptide Y. No displacement is found with the (1-24) N-terminal neuropeptide
      Y fragment, human secretin, porcine dynorphin A and Boc-DAKLI (bolton Hunter
      coupled dynorphin A analog kappa ligand) nor with the non-peptide neuropeptide Y
      receptor antagonist BIBP3266. Gel filtration chromatography and denaturing
      (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) show that the
      [3H]neuropeptide Y-binding component is very likely a single-chain polypeptide
      with a molecular mass of 18.5 kDa.

PMID- 8982677
TI  - Molecular characterization of pharmacological properties of T-0509 for beta
      adrenoceptors.
AB  - The pharmacological properties of T-0509, (-)-(R)-1-(3,4-dihydroxyphenyl)-2-[(3,4
      dimethoxyphenethyl)amino]ethanol, were compared with those of isoproterenol. In
      the radioligand binding studies of [125I]iodocyanopindolol with COS-7 cell
      membranes that transiently expressed beta-adrenoceptor subtypes, T-0509 exhibited
      11- and 97-fold greater Ki values for beta 2- and beta 3-adrenoceptors,
      respectively, compared with beta 1-adrenoceptors. Affinities of beta 2- and beta
      3-adrenoceptors to isoproterenol were 1.4- and 28-fold lower than that of beta 1
      adrenoceptors, respectively. The maximal stimulatory effects of T-0509 on
      adenylyl cyclase of CHO-K1 (chinese hamster ovary K1) cell membranes expressing
      beta 1- or beta 2-adrenoceptors were 85% or 96% of those produced by
      isoproterenol, respectively. These results indicate that T-0509 is a relatively
      specific beta 1-adrenoceptor agonist with a high intrinsic activity as compared
      with isoproterenol.

PMID- 8982678
TI  - 1S,3R-ACPD has cataleptogenic effects and reverses MK-801-, and less pronounced,
      D,L-amphetamine-induced locomotion.
AB  - The purpose of this study was to examine the motor effects of (1S,3R)-1-amino
      cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), an agonist at metabotropic
      glutamate receptors, its interaction with dizocilpine (MK-801), a NMDA receptor
      antagonist, and with D,L-amphetamine, an indirect dopamine receptor agonist.
      1S,3R-ACPD (20, 30, 40, 80 micrograms) evoked prominent locomotor and exploratory
      deficits in an open-field hole-board test and a moderate akinesia and rigidity in
      a catalepsy test (30, 40, 80 micrograms). MK-801 (0.08, 0.16, 0.32 mg/kg i.p.) as
      well as D,L-amphetamine (1.0, 2.0, 3.0 mg/kg i.p.) potently reversed 1S,3R-ACPD
      induced (80 micrograms) catalepsy. MK-801 and D,L-amphetamine, administered
      alone, induced motor stimulation. 1S,3R-ACPD (80 micrograms) reversed the effects
      of the two lower doses of MK-801. 1S,3R-ACPD reversed D,L-amphetamine-induced
      motor stimulation to a minor extent than that of MK-801. Thus motor deficits
      induced by 1S,3R-ACPD were reversed by both, NMDA receptor blockade and dopamine
      receptor activation. 1S,3R-ACPD reversed motor stimulation, induced by NMDA
      receptor blockade and, however less pronounced, that by dopamine receptor
      activation.

PMID- 8982679
TI  - Involvement of delta- and mu-opioid receptors in the potentiation of brain
      stimulation reward.
AB  - A rate-free method of determining brain-stimulation reward thresholds was used to
      identify the rewarding effects of the delta-opioid receptor and mu-opioid
      receptor agonist peptides, [D-Pen2, D-Pen5]enkephalin (DPDPE) and [D-Ala2-MePhe4
      Gly(o1)5]enkephalin (DAMGO). The nucleus accumbens-delivered opioid receptor
      agonists produced marked lowering of the threshold for ventral tegmental area
      brain-stimulation reward. No change in baseline thresholds was seen after
      peripheral administration of the nonpeptide delta-opioid receptor antagonist,
      naltrindole. However, an unexpected finding was that naltrindole blocked the
      threshold-lowering effects of both DPDPE and DAMGO. These data demonstrate
      nucleus accumbens activation of delta- and mu-opioid receptors and ventral
      tegmental area brain-stimulation reward share common brain substrates. In
      addition, the interference of both delta- and mu-opioid receptor mediated reward
      by naltrindole may have implications for therapeutic use.

PMID- 8982680
TI  - Antidepressant-like effects of 1-aminocyclopropanecarboxylic acid and D
      cycloserine in an animal model of depression.
AB  - Antidepressant activity of partial agonists at strychnine-insensitive glycine
      receptors, 1-aminocyclopropanecarboxylic acid (ACPC) and D-cycloserine, was
      studied in a chronic mild stress model of depression. In this model, a
      substantial decrease in consumption of a palatable sucrose solution is observed
      over time in rats subjected to a variety of mild stressors. This decrement can be
      reversed by chronic administration of antidepressant drugs. Chronic (5 weeks)
      treatment with ACPC gradually reversed chronic mild stress-induced reductions in
      sucrose consumption, and the magnitude of this effect was comparable to that
      observed following similar administration of imipramine (10 mg/kg). The time
      course for reversal of chronic mild stress-induced deficits in sucrose
      consumption by ACPC was dose-dependent. Thus, the first statistically significant
      effect of the low dose of ACPC (100 mg/kg) was observed after four weeks of
      treatment (comparable to the 3-5 weeks required for imipramine), while only two
      weeks of treatment was required in the group receiving a higher dose (200 mg/kg)
      of ACPC. Like imipramine, reversal of chronic mild stress-induced deficits in
      sucrose consumption by ACPC persisted for at least one week following cessation
      of treatment. The effects of chronic D-cycloserine were variable, and apparently
      not dose-related in the chronic mild stress model. D-cycloserine (10 mg/kg)
      increased sucrose intake in stressed animals, but the magnitude of this effect
      was smaller than in either imipramine or ACPC treated animals. Lower (2.5 mg/kg)
      and higher (40, 100 mg/kg) doses of D-cycloserine were ineffective. These results
      suggest that ACPC may have antidepressant properties comparable to conventional
      drugs, but with a faster onset of action.

PMID- 8982682
TI  - Involvement of glutamate and gamma-aminobutyric acid (GABA)-ergic systems in
      thyrotropin-releasing hormone-induced rat cerebellar cGMP formation.
AB  - The increase in cyclic guanosine 3',5'-monophosphate (cGMP) caused by
      subcutaneous injection of thyrotropin-releasing hormone (TRH) tartrate was
      observed in a region-specific manner in the rat cerebellum. TRH tartrate (TRH-T)
      (2.8, 7.0 and 17 mg/kg as free TRH, s.c.) produced dose-dependent increases in
      cGMP levels markedly in the cerebellar superior and inferior vermis, and a
      smaller but still significant increase in the cerebellar hemispheres and
      brainstem but no significant increases in other brain regions. The TRH-induced
      increase in the cGMP level in the cerebellum was suppressed by pretreatment with
      muscimol, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one) or MK-801
      (dizocilpine maleate) and partially suppressed by atropine but was not suppressed
      by chlordiazepoxide, oxazepam, phentolamine, propranolol, cyproheptadine,
      haloperidol, baclofen or DNQX (6,7-dinitroquinoxaline-2,3-dione), suggesting the
      possible involvement of GABA (gamma-aminobutyric acid)(A)-ergic, N-methyl-D
      aspartate (NMDA)-type glutamatergic and cholinergic systems. These results
      suggest that excitatory amino acids may be involved in the cGMP formation caused
      by TRH in the cerebellar areas, and that cGMP formation is inhibited by
      enhancement of GABAA receptor function.

PMID- 8982681
TI  - Effects of acute D-CPPene on mesoaccumbens dopamine responses to nicotine in the
      rat.
AB  - Acute administration of the NMDA receptor antagonist, D-CPPene (SDZ EAA 494; 3-(2
      carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid; 2 mg/kg), abolished (P <
      0.01) the sensitised mesoaccumbens dopamine response to nicotine (0.4 mg/kg)
      measured using in vivo microdialysis, but not the increased locomotor activity,
      observed in rats pretreated with nicotine prior to the test day. D-CPPene
      enhanced (P < 0.01) the mesoaccumbens dopamine response, but not the locomotor
      response, to acute nicotine given to drug-naive rats. The data suggest that
      sensitised mesoaccumbens dopamine responses to nicotine involve co-stimulation of
      NMDA receptors but that this effect is not closely related to sensitisation of
      the locomotor response to the drug.

PMID- 8982683
TI  - Involvement of NMDA receptor in the regulation of plasma interleukin-6 levels in
      mice.
AB  - MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclopepten-5,10-imine
      maleate), a non-competitive NMDA receptor antagonist (0.01-1 micrograms),
      injected intracerebroventricularly (i.c.v.) dose dependently increased the
      baseline levels of plasma interleukin-6 in mice. In the 1-h immobilization
      stressed animals, MK-801 (1 micrograms) administered i.c.v. produced an additive
      increase of plasma interleukin-6. NMDA (N-methyl-D-aspartate) (3, 10 ng)
      administered i.c.v. attenuated dose dependently the 1-h immobilization stress
      induced rise in plasma interleukin-6 level. Neither 6-cyano-7-nitro-quinoxaline
      2,3-dione (CNQX) (0.01-0.5 micrograms) nor alpha-methyl-4-carboxyphenylglycine
      (MCPG) (1-20 micrograms), antagonists of non-NMDA and metabotropic glutamate
      receptors, respectively, i.c.v. administered, affected the basal and stress
      induced plasma interleukin-6 levels. These data indicate that NMDA receptors may
      be involved in the suppressive regulation of the plasma interleukin-6 levels.

PMID- 8982685
TI  - The effects of cholinergic drugs on rat neocortical high-voltage spindles in
      ketanserin-treated rats.
AB  - To investigate the roles of the cholinergic system and 5-HT2 receptors in the
      modulation of thalamocortical oscillations, we studied the effects of systemic
      (s.c.) administration of anticholinesterases (physostigmine,
      tetrahydroaminoacridine) and muscarinic acetylcholine receptor agonists
      (pilocarpine, oxotremorine) on spontaneous thalamically generated rhythmic
      neocortical high-voltage spindles in adult rats pretreated with either saline or
      ketanserin, a 5-HT2 receptor antagonist. Ketanserin at 20.0 mg/kg increased the
      number of high-voltage spindles. In saline-treated rats, tetrahydroaminoacridine
      3.0 and 9.0 mg/kg was able to decrease high-voltage spindles, whereas in
      ketanserin 20.0 mg/kg-treated rats only the highest dose of
      tetrahydroaminoacridine (9.0 mg/kg) decreased high-voltage spindles. Both doses
      of physostigmine, 0.12 and 0.36 mg/kg, decreased high-voltage spindles in both
      saline and ketanserin 20.0 mg/kg-treated rats. Lower doses of
      tetrahydroaminoacridine (1.0 mg/kg) and physostigmine (0.06 mg/kg) were
      ineffective in both saline- and ketanserin 20.0 mg/kg-treated rats. Pilocarpine
      3.0 mg/kg and oxotremorine 0.1 and 0.9 mg/kg decreased high-voltage spindles in
      saline-treated rats. However, in rats treated with ketanserin 20.0 mg/kg, only
      the lower doses of pilocarpine (0.3 and 1.0 mg/kg) and oxotremorine (0.03 mg/kg)
      were able to decrease the high-voltage spindles. The results suggest that
      activation of the cholinergic system and activation of 5-HT2 receptors have
      additive effects in the suppression of thalamocortical oscillations and related
      neocortical high-voltage spindles in rats, thus maintaining effective information
      processing in thalamocortical networks.

PMID- 8982684
TI  - Postischemic administration of adenosine amine congener (ADAC): analysis of
      recovery in gerbils.
AB  - Although adenosine receptor-based treatment of cerebral ischemia and other
      neurodegenerative disorders has been frequently advocated, cardiovascular side
      effects and an uncertain therapeutic time window of such treatment have
      constituted major obstacles to clinical implementation. Therefore, we have
      investigated the neuroprotective effects of the adenosine A1 receptor agonist
      adenosine amine congener (ADAC) injected after either 5 or 10 min ischemia at 100
      micrograms/kg. When the drug was administered at either 6 or 12 h following 5 min
      forebrain ischemia, all animals were still alive on the 14th day after the
      occlusion. In both ADAC treated groups neuronal survival was approximately 85%
      vs. 50% in controls. Administration of a single dose of ADAC at times 15 min to
      12 h after 10 min ischemia resulted in a significant improvement of survival in
      animals injected either at 15 or 30 min, or at 1, 2, or 3 h after the insult. In
      all 10 min ischemia groups, administration of ADAC resulted in a significant
      protection of neuronal morphology and preservation of microtubule associated
      protein 2 (MAP-2). However, postischemic Morris' water maze tests revealed full
      preservation of spatial memory and learning ability in animals injected at 6 h.
      On the other hand, the performance of gerbils treated at 12 h postischemia was
      indistinguishable from that of the controls. Administration of ADAC at 100
      micrograms/kg in non-ischemic animals did not result in bradycardia, hypotension,
      or hypothermia. The data indicate that when ADAC is used postischemically, the
      most optimal level of protection is obtained when drugs are given at 30 min to 6
      h after the insult. Although the mechanisms involved in neuroprotective effects
      of adenosine A1 receptor agonists require further studies, the present results
      demonstrate the feasibility of their clinical applications.

PMID- 8982686
TI  - Interaction of S 21007 with 5-HT3 receptors. In vitro and in vivo
      characterization.
AB  - The interaction of S 21007 [5-(4-benzyl piperazin-1-yl)4H pyrrolo [1,2
      a]thieno[3,2-e]pyrazine] with serotonin 5-HT3 receptors was investigated using
      biochemical, electrophysiological and functional assays. Binding studies using
      membranes from N1E-115 neuroblastoma cells showed that S 21007 is a selective
      high affinity (IC50 = 2.8 nM) 5-HT3 receptor ligand. As expected of an agonist, S
      21007 stimulated the uptake of [14C]guanidinium (EC50 approximately 10 nM) in NG
      108-15 cells exposed to substance P, and this effect could be prevented by the
      potent 5-HT3 receptor antagonist ondansetron. In addition, like 5-HT and other 5
      HT3 receptor agonists (phenylbiguanide and 3-chloro-phenylbiguanide), S 21007
      (EC50 = 27 microM) produced a rapid inward current in N1E-115 cells. The 5-HT3
      receptor agonist action of S 21007 was also demonstrated in urethane
      anaesthetized rats as this drug (120 micrograms/kg i.v.) triggered the Bezold
      Jarisch reflex (rapid fall in heart rate), and this action could be prevented by
      pretreatment with the potent 5-HT3 receptor antagonist zacopride. Finally, in
      line with its 5-HT3 receptor agonist properties, S 21007 also triggered emesis in
      the ferret. Evidence for 5-HT3 receptor antagonist-like properties of S 21007 was
      also obtained in some of these experiments since previous exposure to this
      compound prevented both the 5-HT-induced current in N1E-115 cells and the Bezold
      Jarisch reflex elicited by an i.v. bolus of 5-HT (30 micrograms/kg) in urethane
      anaesthetized rats. These data suggest that S 21007 is a selective 5-HT3 receptor
      agonist which can exhibit antagonist-like properties either by triggering a long
      lasting receptor desensitization or by a partial agonist activity at 5-HT3
      receptors in some tissues.

PMID- 8982687
TI  - Spinal administration of adrenergic agents produces analgesia in amphibians.
AB  - Direct intraspinal injection of the catecholamines epinephrine and
      norepinephrine, and the alpha-adrenergic agents dexmedetomidine and clonidine,
      produced a dose-dependent elevation of pain thresholds in the Northern grass
      frog, Rana pipiens. Significant analgesic effects were noted for at least 4 h.
      The analgesic effect of intraspinal dexmedetomidine or epinephrine was blocked by
      systemic pretreatment with the alpha 2-adrenoceptor antagonists, yohimbine and
      atipamezole, but not with the alpha 1-adrenoceptor antagonist, prazosin. Dose
      response analyses showed that dexmedetomidine, epinephrine, norepinephrine had
      similar analgesic potencies, but clonidine was significantly less potent.
      Analgesia was observed without accompanying motor or sedative effects. These
      results suggest that alpha 2-adrenoceptor mechanisms which mediate analgesia may
      have evolved early in vertebrate evolution and that descending epinephrine
      containing fibers in the amphibian nervous system may be the source of endogenous
      catecholamines regulating nociceptive sensitivity in the amphibian spinal cord.

PMID- 8982689
TI  - Nitroprusside decreases the early post-denervation depolarization of diaphragm
      muscle fibres of the rat.
AB  - The application of sodium nitroprusside, which degrades to nitric oxide (NO) in
      solution, inhibits early post-denervation depolarization of isolated rat
      diaphragm fibres. The observation that "old' solutions of sodium nitroprusside
      (that have been allowed to decompose) are without effect and that haemoglobin,
      oxadiazolo quinoxalinone (ODQ) and methylene blue can antagonize the inhibition
      normally produced by sodium nitroprusside suggests that the inhibitory effects of
      sodium nitroprusside on early post-denervation depolarization are mediated by NO
      and guanylyl cyclase. This is in accord with our recent observations with NO
      synthase activation and inhibition in the diaphragm.

PMID- 8982688
TI  - The anticonvulsant gabapentin decreases firing rates of substantia nigra pars
      reticulata neurons.
AB  - Gabapentin is a novel anti-epileptic drug which enhances GABA (gamma-aminobutyric
      acid) turnover in certain brain regions, including substantia nigra. However, the
      functional consequences of GABA turnover increases in response to gabapentin and
      their potential involvement in the anticonvulsant action of this drug are not
      known. In the present study, we examined the effects of gabapentin on the
      extracellular, single unit activity of nondopaminergic (presumably GABAergic)
      neurons of the substantia nigra pars reticulata in rats. During the recordings,
      the animals were infused with the narcotic opioid analgesic fentanyl, associated
      with a skeletal muscle relaxant and artificial ventilation. The spontaneous
      firing of substantia nigra pars reticulata neurons was determined up to about 2 h
      after i.v. or i.p. administration of gabapentin at doses of 15-30 mg/kg. After
      both routes of administration, gabapentin markedly reduced neuronal firing when
      administered at a dose of 20-30 mg/kg, while 15 mg/kg were ineffective in this
      regard. The suppressive effect of gabapentin was rapid in onset (2 min after i.v.
      and about 20 min after i.p. injection), reached peak values of about 70% below
      predrug baseline after about 45-60 min, and remained at this level for at least 2
      h. Vehicle administration had no effect on substantia nigra pars reticulata
      neurons. The ability of gabapentin to alter substantia nigra pars reticulata
      firing does correlate with its known ability to increase nigral GABA turnover.
      Since a substantial body of evidence suggests that the substantia nigra pars
      reticulata is a critical site at which decrease of neuronal firing by
      potentiation of GABAergic influences results in protection against various
      seizure types, the suppressive effect of gabapentin on substantia nigra pars
      reticulata activity may contribute to the anticonvulsant action of this drug.

PMID- 8982690
TI  - Extracellular K+ and protection against cellular damage in the rat heart.
AB  - Rat hearts were perfused at 37 degrees C with three clearly-defined protocols:
      the Ca2+ paradox, the O2 paradox and with 20 mM caffeine. Each protocol involved
      an initial priming (stage 1) and a subsequent full activation (stage 2) of the
      damage system of the sarcolemma. Raising [K+]o from 5.4 to 6.5 mM in the Ca2+
      paradox had no significant effect, but creatine kinase release was significantly
      inhibited (P < 0.001) at 7.5, 10.8 or 16.2 mM. Raising [K+]o to 16.2 mM only
      during stage 1 or only during stage 2 also inhibited creatine kinase release (P <
      0.001); protection was greater than when 16.2 mM [K+]o was present throughout.
      [K+]o at 10.8 mM exacerbated creatine kinase release in the O2 paradox (P <
      0.001) and also when present only during stage 1. However, significant protection
      was provided when [K+]o was raised only during stage 2 (P < 0.001). Creatine
      kinase release in the caffeine protocol was significantly inhibited (P < 0.001)
      at 10.8 mM [K+]o and when [K+]o was raised only during stage 1 or stage 2. It is
      concluded that raised [K+]o has two opposing effects: prevention of the
      activation of the membrane damage system and an exacerbation of damage via an
      increased Ca2+ influx.

PMID- 8982691
TI  - The effects of P2 purinoceptor agonists on the isolated portal vein of the guinea
      pig.
AB  - UTP, ATP and several of its analogues enhanced contractions of the longitudinal
      smooth muscle layer of the guinea-pig portal vein. The rank order of potency was
      2-methylthioATP > alpha, beta-methyleneATP > adenosine tetraphosphate > or =
      beta, gamma-methyleneATP > or = ATP = UTP > > adenosine. Suramin (100 microM)
      blocked the contractile effects of 2-methylthioATP and alpha,beta-methyleneATP,
      but not those of ATP and adenosine tetraphosphate. The P1 purinoceptor
      antagonist, 8-phenyltheophylline (10 microM), was without effect on the response
      to ATP. Field stimulation (5 s trains every 100 s, 1 ms, 55 V) caused frequency
      dependent contractions that were partially reduced by the noradrenergic neurone
      blocking drug; BW 172C58 (4-benzoyl-xylocholine, 10 microM), but not by suramin.
      alpha,beta-MethyleneATP was more potent than beta,gamma-methyleneATP, UTP and
      adenosine tetraphosphate in partially inhibiting field stimulation-induced
      contractions of the portal vein; its effects, but not those of adenosine
      tetraphosphate, were reduced by suramin. These results indicate that the guinea
      pig portal vein contains P2 purinoceptors; these include a P2x subtype, mediating
      contraction.

PMID- 8982692
TI  - Increases in inotropic state without change in heart rate: combined use of
      dobutamine and zatebradine in conscious dogs.
AB  - The cardiovascular and left ventricular functional effects of dobutamine (5, 10
      and 20 micrograms kg-1 min-1) were examined in conscious, chronically
      instrumented dogs in the presence and absence of control of heart rate with the
      specific bradycardic agent, zatebradine. Dobutamine increased heart rate, cardiac
      output, stroke volume, diastolic coronary blood flow velocity and pressure-work
      index (calculated myocardial oxygen consumption) and decreased systemic vascular
      resistance and diastolic coronary vascular resistance. Mean arterial pressure and
      left ventricular systolic and end-diastolic pressures were unchanged. Dobutamine
      induced increases in heart rate and pressure-work index were attenuated by
      zatebradine. Dobutamine alone increased preload recruitable stroke work slope (63
      +/- 6 to 116 +/- 11 mmHg) and +dP/dt. These positive inotropic effects were
      unaffected by zatebradine. Dobutamine decreased the time constant of isovolumic
      relaxation (30 +/- 3 to 25 +/- 2 ms). Dobutamine-induced decreases in the time
      constant of isovolumic relaxation were not altered by zatebradine, indicating
      that changes in the time constant occurred independent of heart rate. Dobutamine
      also increased the maximal segment lengthening velocity to a similar degree in
      zatebradine-treated versus untreated dogs. Control of dobutamine-induced
      tachycardia by zatebradine decreases myocardial oxygen consumption but does not
      alter the positive inotropic and lusitropic effects of dobutamine.

PMID- 8982693
TI  - Cardiovascular responses induced by injection of endothelin-1 into the superior
      colliculus of rats.
AB  - Microinjection of endothelin-1 (1-10-100 pmol) into the superficial layer of the
      superior colliculus of anaesthetised rats caused dose-dependent decreases in
      blood pressure. This is unlikely to be a non-specific effect, for angiotensin II
      (1 nmol) caused increases in blood pressure. Injection of endothelin-1 (10 pmol)
      into the superior colliculus also caused falls in renal blood flow as measured by
      an ultrasonic flow probe. Decreases in blood pressure and falls in renal blood
      flow induced by injection of endothelin-1 into the superior colliculus were
      unaffected by bilateral vagotomy suggesting that attenuations in the activity of
      the sympathetic nervous system were involved in these events.

PMID- 8982694
TI  - Mivazerol, a selective alpha 2-adrenoceptor agonist, attenuates tachycardia by
      intrathecal injection of N-methyl-D-aspartate in the rat.
AB  - The intravenous (i.v.) infusion of mivazerol, a new selective alpha 2
      adrenoceptor agonist, produced a significant decrease in heart rate but not in
      blood pressure in pentobarbital-anesthetized Sprague-Dawley rats. The tachycardic
      response to intrathecal (i.t.) injection of N-methyl-D-aspartic acid (NMDA) was
      significantly attenuated by the i.v. infusion of mivazerol. The i.t. pretreatment
      with yohimbine significantly attenuated the bradycardic response to i.v.
      mivazerol and blocked the effect of mivazerol on the tachycardic response to i.t.
      NMDA. These results suggest that (1) the bradycardic effect of mivazerol is
      mediated, at least partly, by spinal alpha 2-adrenoceptors; and (2) there is a
      possibility of functional antagonism between spinal alpha 2-adrenoceptors and
      NMDA receptors in the regulation of heart rate.

PMID- 8982696
TI  - Involvement of K+ channel modulation in the proabsorptive effect of nitric oxide
      in the rat jejunum in vivo.
AB  - The role of K+ channels in the mediation of the nitric oxide(NO)-induced
      proabsorptive effect in intestinal fluid transport was investigated in a
      functional study, using a model of ligated jejunal loops of anaesthetized rats in
      vivo. The K+ channel opener cromakalim and the K+ channel blocker glibenclamide
      were administered under basal conditions as well as under conditions, when fluid
      secretion was influenced by N omega-nitro-L-arginine methyl ester (L-NAME),
      prostaglandin E2, Escherichia coli heat stable enterotoxin a (E. coli STa) or L
      arginine. Intravenous infusion of cromakalim (63.5 micrograms/kg per min)
      significantly enhanced net fluid absorption compared to controls, totally
      abolished net fluid secretion induced by L-NAME (0.55 mg/kg per min), reversed
      net fluid secretion induced by intraluminal instillation of E. coli STa (10
      units/ml) to absorption, but did not influence fluid secretion elicited by close
      i.a. infusion of prostaglandin E2 (79 ng/min). Close i.a. infusion of
      glibenclamide (0.16 mg/kg per min) reversed net fluid absorption to net
      secretion, blocked the absorptive effect of L-arginine (8.88 mg/kg per min) and
      reduced the proabsorptive effect of cromakalim. The secretory effect of L-NAME
      was not further enhanced by glibenclamide. These results suggest that modulation
      of basolateral K+ channels by NO is involved in the mediation of its
      proabsorptive effect, since opening and closure of K+ channels mimicked,
      respectively counteracted, the action of NO-donors and inhibitors of NO-synthesis
      on intestinal fluid transport. The role of prostaglandins in the proabsorptive
      effect of NO remains to be elucidated. These results furthermore support the role
      of K+ channel openers as potential new antidiarrheal drugs.

PMID- 8982695
TI  - Gastrointestinal actions of buprenorphine: are different receptors involved?
AB  - The effects of buprenorphine on castor-oil-induced diarrhoea, gastrointestinal
      transit and ethanol-induced gastric lesions in rats were compared to the same
      effects of morphine. Like morphine, buprenorphine prevented castor-oil-induced
      diarrhoea. However, it has no effect on gastrointestinal transit per se but
      prevented the inhibitory action of morphine. While morphine protected against
      ethanol-induced gastric lesions, buprenorphine aggravated them. It is suggested
      that different types/subtypes of opioid receptors may be involved in the
      gastrointestinal actions of buprenorphine.

PMID- 8982697
TI  - Analysis of the bronchoconstrictor responses to adenosine receptor agonists in
      sensitized guinea-pig lungs and trachea.
AB  - Airway perfused lungs and half-lungs and superfused tracheal spirals from
      ovalbumin-sensitized guinea pigs were set up. Adenosine and the analogues, 5'-(N
      ethylcarboxamido)adenosine (NECA), R-N6-phenylisopropyladenosine (R-PIA), 2
      chloroadenosine, N6-2-(4-aminophenyl)ethyladenosine (APNEA) and 5'-AMP yielded
      bronchoconstrictor responses as increases in perfusion pressure or of tension,
      respectively, of these two preparations. These responses were greater in tissues
      from sensitized compared with un-sensitized guinea pigs. Cross-tachyphylaxis
      occurred between the constrictor responses to adenosine and the other constrictor
      adenosine agonists which indicated a common site of action. The adenosine
      transport inhibitors, dipyridamole and S-(p-nitrobenzyl)-6-thioinosine (NBTI),
      inhibited the constrictor responses to adenosine and the analogues, except 2
      chloroadenosine. This was attributed to a potentiation of the opposing relaxant
      effects which generally occurred at higher concentrations of the agonists. The P1
      purinoceptor antagonists 8-phenyltheophylline and 8-cyclopentyltheophylline (A1
      receptor selective) failed to remove the constrictor responses to adenosine
      either alone or in the presence of dipyridamole. This suggests that the
      bronchoconstrictor response of sensitized airways tissues is mediated via the
      novel xanthine-resistant A3 receptor.

PMID- 8982698
TI  - Melatonin together with noradrenaline augments contractions of human myometrium.
AB  - The hormone melatonin is known to influence the circadian rhythm, and it probably
      also mediates some of the physiological changes that occur in the body at night.
      Inasmuch as uterine activity is greater during darkness, we investigated whether
      melatonin could modulate uterine contractility. Biopsies were performed during
      caesarean sections to obtain uterine tissue from women who had reached full term.
      The obtained samples were mounted in organ baths, and spontaneous contractions
      were recorded. Melatonin alone did not change myometrial contractility, whereas
      melatonin in combination with noradrenaline potentiated contractions. These
      results may indicate that melatonin plays a role in the timing of labour, since
      labour often begins late in the evening.

PMID- 8982699
TI  - Antioedematogenic and antinociceptive actions of NPC 18521, a novel bradykinin B2
      receptor antagonist.
AB  - The novel pseudopeptide bradykinin B2 receptor antagonist containing the 1,3,8
      triazaspiro[4,5]decan-4-one ring system, NPC 18521 (D-Arg-Arg-[1,3-phenyl,8
      triazaspiro[4,5]-decane-4-one-3-acetyl]-S er-D -tetrahydroisoquinolinyl
      octahydroindolinyl-Arg) (10 and 30 nmol/kg, i.p.), given 30 min prior, produced
      significant and long-lasting inhibition of rat paw oedema induced by bradykinin
      (3 nmol/paw) and carrageenan (300 micrograms/paw), without affecting the oedema
      induced by the selective bradykinin B1 receptor agonist, des-Arg9-bradykinin, in
      rats pretreated with Escherichia coli endotoxin. In contrast, when injected
      locally into the rat or mouse hindpaw, NPC 18521 (1-100 nmol) elicited dose
      related oedema formation. This effect was almost completely blocked by
      cyproheptadine (20 mg/kg, i.p.) or by compound 48/80 (12 micrograms/paw), but was
      unaffected by Hoe 140 (D-Arg-[Hyp5,Thi5,Tic7,Oic8]bradykinin). NPC 18521 (0.3-10
      nmol/kg, i.p.) produced significant inhibition of acetic acid, acetylcholine and
      kaolin- but not zymosan-induced abdominal constrictions in mice. The calculated
      mean ID50 values for these effects were 0.84, 0.46 and 0.55 nmol/kg,
      respectively. The antinociceptive action of NPC 18521 (3 nmol/kg, i.p.) had a
      rapid onset (15 min) and lasted for up to 120 min. Given topically (0.01-0.3
      nmol), NPC 18521 produced significant attenuation of both the early and the late
      phase of the formalin-induced licking, as well as formalin-induced oedema
      formation. In addition, NPC 18521 given both systemically or topically, produced
      significant inhibition of the neurogenic nociception caused by topical injection
      of capsaicin. Given topically in the rat paw, NPC 18521 (10 nmol) caused marked
      hyperalgesia, an effect which was completely prevented by cyproheptadine (20
      mg/kg, i.p.), but was unaffected by Hoe 140 (3 nmol/kg, i.p.). Given
      intraperitoneally, 30 min prior, NPC 18521 (3-30 nmol/kg) like Hoe 140 (1-10
      nmol/kg) prevented, in a dose-dependent manner, bradykinin (3 nmol/paw)-induced
      hyperalgesia with mean ID50 values of 13.16 and 1.36 nmol/kg, respectively. Thus,
      the novel pseudopeptide bradykinin B2 receptor antagonist, NPC 18521, has an
      effect with rapid onset, and produces potent and relatively long-lasting
      antioedematogenic and antinociceptive properties. However, in contrast to Hoe
      140, given locally into the hindpaw, NPC 18521 elicited marked oedema formation
      and hyperalgesia, an effect which seems to be secondary to mast cell
      degranulation and histamine and/or serotonin release. Finally, the anti
      bradykinin actions of NPC 18521 are quite selective towards the bradykinin B2
      receptor-mediated responses.

PMID- 8982700
TI  - Expression of inducible nitric oxide synthase in mice: pharmacological evaluation
      of adenosine receptor agonists.
AB  - Inhibition of inducible nitric oxide (NO) synthase during endotoxaemia may be of
      therapeutic value. We have previously shown that pretreatment of mice with
      adenosine receptor agonists 1 h before lipopolysaccharide administration results
      in a dose-dependent reduction of plasma nitrite and nitrate (NOx-) levels. This
      report examines the effects of adenosine receptor agonists, 5'-N
      ethylcarboxamidoadenosine (NECA), N6-cyclohexyladenosine (CHA), R-phenylisopropyl
      adenosine (R-PIA) and 5'-(N-cyclopropyl)carboxamidoadenosine (CPCA), on the level
      of inducible NO synthase expression in a model of liver inflammation induced by
      lipopolysaccharide. Following lipopolysaccharide administration (10 mg/kg, i.p.),
      liver mRNA expression peaked at 3 h and declined to 35% of maximal level after 24
      h. Pretreatment with adenosine receptor agonists (0.001 mg/kg to 5 mg/kg, i.p.)
      depressed inducible NO synthase mRNA expression significantly. Down-regulation of
      inducible NO synthase mRNA expression corresponded with changes in plasma NOx-
      level as well as activity of NO synthase in the liver. Administration of R-PIA (5
      mg/kg, i.p.) increased the survival of animals injected with a lethal dose of
      lipopolysaccharide. Thus adenosine receptor agonists may useful as anti
      inflammatory agents in the treatment of endotoxaemia.

PMID- 8982701
TI  - Butein (3,4,2',4'-tetrahydroxychalcone) ameliorates experimental anti-glomerular
      basement membrane antibody-associated glomerulonephritis (3).
AB  - The antinephritic effects of butein (3,4,2',4'-tetrahydroxychalcone) on original
      type anti-glomerular basement membrane antibody-associated glomerulonephritis in
      rats were investigated. Butein was given to anti-glomerular basement membrane
      antibody-associated glomerulonephritic rats for 15 days after the induction of
      nephritis. Butein prevented proteinuria and histological alterations. The up
      regulation of intercellular adhesion molecule-1 (ICAM-1) expression and increase
      in leukocyte function-associated antigen-1 (LFA-1) positive cells in nephritic
      glomeruli significantly declined with butein treatment. In the further
      investigation to clarify the effects of butein on ICAM-1 expression, human
      umbilical vein endothelial cells were treated with butein in the presence of
      tumor necrosis factor-alpha (TNF-alpha) or phorbol 12-myristate 13-acetate (PMA).
      Butein prevented the up-regulation of ICAM-1 expression mediated by TNF-alpha or
      PMA on human umbilical vein endothelial cells in a dose-dependent manner. When
      human umbilical vein endothelial cells or neutrophils were treated with butein,
      the adhesion of neutrophils to human umbilical vein endothelial cells was
      suppressed. These data suggest that the antinephritic action of butein is due to
      inhibition of intraglomerular accumulation of leukocytes through the prevention
      of the up-regulation of ICAM-1 and the inhibition of a function of adhesion
      molecules on the surface of leukocytes.

PMID- 8982702
TI  - Inhibitory effects of berberine on ATP-sensitive K+ channels in cardiac myocytes.
AB  - The effects of berberine on cardiac action potentials were measured in isolated
      guinea-pig papillary muscles exposed to hypoxia and cromakalim using the standard
      microelectrode technique. In addition, the patch clamp technique was used to
      determine the effects of berberine on cromakalim-induced outward currents in
      isolated ventricular myocytes and on ATP-sensitive K+ (KATP) channels in inside
      out membrane patches. Berberine, at 3 microM significantly inhibited, while at
      100 microM completely blocked the shortening of action potential duration and
      effective refractory period induced by hypoxia or cromakalim (100 microM). Under
      the whole-cell voltage clamp conditions, berberine (3-100 microM) attenuated or
      even abolished the cromakalim-elicited outward K+ currents. Berberine (3-100
      microM) inhibited KATP channel activity in a concentration-dependent fashion in
      inside-out membrane patches exposed to 0.1 mM ATP. This inhibition appeared to be
      mainly due to a decrease in the open channel probability without affecting
      unitary conductance or the time constants for open and closed channel times.
      Glibenclamide (10 microM) partially blocked the hypoxia-evoked but fully reversed
      the cromakalim-evoked abbreviation of action potential duration and effective
      refractory period. Both the whole-cell outward K+ currents induced by cromakalim
      and the opening of single KATP channels induced by the low intracellular ATP
      concentration were also completely abolished by 10 microM glibenclamide. We
      conclude that berberine is a blocker of the cardiac KATP channel. The reported
      beneficial effect of berberine on ischemia-induced arrhythmias is likely
      attributed to its inhibition of KATP channel activation and subsequent shortening
      of action potential duration and effective refractory period during ischemia.

PMID- 8982703
TI  - 90-kDa S6 kinase is insufficient or not involved in the activation of glycogen
      synthase induced by insulin.
AB  - Insulin and growth factors increase glycogen synthesis via complex pathways
      including protein phosphorylation/dephosphorylation processes. We investigated
      the involvement of 90-kDa S6 kinase in the control of insulin- or epidermal
      growth factor (EGF)-stimulated glycogen synthase activation using newly
      synthesized compounds which selectively inhibit 90-kDa S6 kinase. HH-5709 (1-(5
      hydroxynaphthalenesulfonyl)-1H-hexahydro-1,4-diazepine) inhibited 90-kDa S6
      kinase at lower concentrations than observed for protein kinases A or C. The
      inhibition by HH-5709 was competitive with respect to ATP with a Ki value of 1.3
      microM. H-7, an inhibitor of protein kinases A and C, and HA-1077 (1-(5
      isoquinolinesulfonyl)-homopiperazine), where the naphthalene ring of HH-5709 was
      replaced with isoquinoline, also inhibited 90-kDa S6 kinase to a similar extent
      as HH-5709. In 3Y1 fibroblasts, H-7 and HA-1077 attenuated the activation of
      glycogen synthase. HH-5709, however, failed to affect the glycogen synthase
      activation by either insulin or EGF. These findings suggest that 90-kDa S6 kinase
      is unrelated or insufficient to mediate activation of glycogen synthase and that
      unidentified pathway(s) sensitive to H-7 or HA-1077 would be involved in the
      activation of glycogen synthase by insulin or EGF in 3Y1 fibroblasts.

PMID- 8982704
TI  - Adenosine A2A receptors modulate the binding characteristics of dopamine D2
      receptors in stably cotransfected fibroblast cells.
AB  - In membrane preparations from rat striatum, where adenosine A2A and dopamine D2
      receptors are coexpressed, stimulation of adenosine A2A receptors was found to
      decrease the affinity of dopamine D2 receptors for dopamine agonists. We now
      demonstrate the existence of this antagonistic interaction in a fibroblast cell
      line (Ltk-) stably transfected with the human dopamine D2 (long-form) receptor
      and the dog adenosine A2A receptor cDNAs (A2A-D2 cells). In A2A-D2 cells, but not
      in control cells only containing dopamine D2 receptors (D2 cells), the selective
      adenosine A2A agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethyl
      carboxamido adenosine (CGS 21680) induced a 2-3-fold decrease in the affinity of
      dopamine D2 receptors for dopamine, as shown in competition experiments with
      dopamine versus the selective dopamine D2 antagonist [3H]raclopride. By contrast,
      activation of the constitutively expressed adenosine A2B receptors with 5'-N
      ethyl-carboxamidoadenosine (NECA) did not modify dopamine D2 receptor binding. In
      A2A-D2 cells CGS 21680 failed to induce or induced only a small increase in
      adenosine-3',5'-cyclic-monophosphate (cAMP) accumulation. In D2 cells NECA- or
      forskolin-induced adenylyl cyclase activation was not associated with any change
      in dopamine D2 receptor binding. These results indicate that adenylyl cyclase
      activation is not involved in the adenosine A2A receptor-mediated modulation of
      the binding characteristics of the dopamine D2 (long-form) receptor.

PMID- 8982705
TI  - Effects of dantrolene sodium on intracellular Ca2(+)-handling in normal and
      Ca2(+)-overloaded cardiac muscle.
AB  - We investigated the effects of dantrolene sodium on intracellular Ca2+
      homeostasis in normal and Ca2+ overloaded rat cardiac muscle. In isometrically
      contracting rat papillary muscles loaded with the Ca2+ indicator aequorin,
      dantrolene (50 microM) produced a mild negative inotropic effect (28 +/- 1.8 to
      21 +/- 1.1 mN/mm2; mean +/- S.E.; n = 6; P < 0.01), which was paralleled by a
      decrease in peak systolic [Ca2+]i (0.81 +/- 0.04 to 0.67 +/- 0.04 microM; P <
      0.01). In isolated cardiac sarcoplasmic reticulum, dantrolene (50 microM)
      increased the initial Ca2+ uptake rate by 23% as compared to control preparations
      (at pCa 6.2: 46.9 +/- 1.6 to 61.1 +/- 2.2 nmol/mg per min; n = 4; P < 0.001).
      Intracellular Ca2+ overload was provoked in isoproterenol-pretreated (100 microM)
      preparations with [Ca2+]o = 5.0 mM at a stimulation rate of 1.0 Hz (n = 12).
      Diastolic Ca2+ oscillations and aftercontractions increased mean diastolic
      [Ca2+]i (0.33 +/- 0.1 to 0.56 +/- 0.1 microM) and tension (9.5 +/- 1.8 to 15.3 +/
      2.1 mN/mm2), respectively. Addition of dantrolene (50 microM) reduced the
      amplitude of Ca2+ oscillations and aftercontractions; mean diastolic [Ca2+]i
      decreased to 0.44 +/- 0.1 microM and diastolic tension to 13.5 +/- 2.2 mN/mm2. We
      conclude, therefore, that dantrolene sodium modifies Ca2+ handling by the
      myocardial sarcoplasmic reticulum, an effect that might be useful in cardiac
      disorders with impaired [Ca2+]i homeostasis.

PMID- 8982706
TI  - Ibogaine and noribogaine potentiate the inhibition of adenylyl cyclase activity
      by opioid and 5-HT receptors.
AB  - The effects of the putative anti-addictive compound ibogaine and its principal
      metabolite, noribogaine, on adenylyl cyclase activity were determined in various
      areas of the rat brain. Neither compound altered either basal or forskolin
      stimulated adenylyl cyclase activities in the frontal cortex, midbrain or
      striatum. However, in all three brain areas the addition of ibogaine and
      noribogaine significantly enhanced inhibition of adenylyl cyclase activity by a
      maximally effective concentration of morphine. Similarly, both compounds also
      potentiated the inhibition of hippocampal adenylyl cyclase activity by a
      maximally effective concentration of 5-hydroxytryptamine (5-HT). Although
      ibogaine appears to be more potent than noribogaine in augmenting opioid- and 5
      HT-mediated inhibition of adenylyl cyclase activity, both compounds appear to be
      of comparable efficacy. Neither compound, however, modified the inhibitory action
      of the muscarinic acetylcholine agonist, carbachol, on adenylyl cyclase activity.
      The present data indicate that ibogaine and noribogaine cause a selective
      increase in receptor-mediated inhibition of adenylyl cyclase activity. This
      potentiation may be involved in the pharmacological actions of these compounds.

PMID- 8982707
TI  - Eicosanoid inhibitors enhance synergistically the effect of transforming growth
      factor beta 1 on CCL 64 cell proliferation.
AB  - The interactions between drugs suppressing the production of arachidonic acid
      metabolites-eicosanoids and transforming growth factor beta 1 (TGF-beta 1) were
      investigated using CCL64 cells. These experiments, designed as complete factorial
      combination of treatments, demonstrated that both esculetin and eicosatetraynoic
      acid significantly potentiated the inhibitory effect of TGF-beta 1 on
      [3H]thymidine incorporation. The expression of overadditive effects depended both
      on the type and concentration of combined factors. These results corresponded
      with cell cycle analysis data (increased cell number in G1 and decreased cell
      number in S and G2/M phases) and with the results monitoring cell number
      following treatment with eicosatetraynoic acid, esculetin, 3-[1-(4-chlorobenzyl)
      3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-di methyl propanoic acid (MK-886) and
      indomethacin. Summarizing, the degree of significance of combined effects
      supports the hypothesis of synergistic potentiation of TGF-beta 1 effects caused
      by eicosanoid inhibitors. The results indicate that either the lack of some
      eicosanoids or a certain type of misbalance in the metabolism of arachidonic acid
      leading to its abundance might modulate TGF-beta 1 effects on the cell cycle and
      proliferation in CCL64 cells.

PMID- 8982708
TI  - [3H]RX821002 (2-methoxyidazoxan) binds to alpha 2-adrenoceptor subtypes and a non
      adrenoceptor imidazoline binding site in rat kidney.
AB  - The binding of [3H]RX821002 (2-methoxyidazoxan) was evaluated in rat kidney
      membranes. [3H]RX821002 (0.13-16 nM) recognized a single, saturable binding site
      with high affinity. Different binding site densities were calculated depending on
      non-specific binding as defined by (-)-adrenaline or RX821002 (10 microM).
      Competition assays using (-)-adrenaline and the subtype-selective drugs ARC 239
      (2-[2-[4-(o-methoxyphenyl)-piperazin-1-yl]-ethyl]-4,4-dimethyl-1,3 (2H,4H)
      isoquinolindione), BRL 44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5
      dihydroimidaz ole), oxymetazoline or prazosin for [3H]RX821002 binding sites
      revealed the presence of alpha 2B-adrenoceptors (33-51%), alpha 2D-adrenoceptors
      (15-28%) and an adrenaline-insensitive population (34-40%), sensitive to
      imidazolines. After the addition of (-)-adrenaline (3 microM) to mask alpha 2
      adrenoceptors, [3H]RX821002 specifically identified a saturable binding site with
      high affinity (Kd = 4.9 +/- 1.5 nM). The pharmacological profile of this non
      adrenoceptor, [3H]RX821002 binding site (potencies: efaroxan > clonidine >
      guanabenz > BRL 44408 > ARC 239 > BU 224 (2-(4,5-dihydroimidaz-2-yl)quinoline) >
      moxonidine > (-)-nor-adrenaline > cimetidine) is different to that of imidazoline
      I1 or imidazoline I2 binding sites. Alternative incubation in the presence of ARC
      239 (50 nM) to mask alpha 2B-adrenoceptors or BRL 44408 (100 nM) to mask alpha 2D
      adrenoceptors confirmed the existence of both alpha 2-adrenoceptor subtypes and a
      non-adrenoceptor imidazoline binding site.

PMID- 8982709
TI  - Tramadol, M1 metabolite and enantiomer affinities for cloned human opioid
      receptors expressed in transfected HN9.10 neuroblastoma cells.
AB  - Tramadol hydrochloride is a centrally acting synthetic analgesic in widespread
      clinical use. Despite different degrees of opioid-like characteristics in
      preclinical tests, it is characterized by lack of full naloxone reversibility or
      naloxone-precipitated withdrawal in humans. To investigate this apparent
      discrepancy, the present study measured the affinity of tramadol (and its
      enantiomers) and an active O-desmethyl metabolite (M1) (and its enantiomers) to
      cloned human opioid receptors of the mu, delta and kappa type stably expressed in
      HN9.10 neuroblastoma cells. At mu sites, the Ki values for tramadol, its (+) and
      (-) enantiomers, M1, and its (+) and (-) enantiomers were 17000, 15700, 28800,
      3190, 153 and 9680 nM, respectively, compared to 7.1 nM for morphine. These
      results are consistent with the suggestion of a non-opioid contribution to the
      clinical profile of tramadol.

PMID- 8982710
TI  - Felbamate inhibits cloned voltage-dependent Na+ channels from human and rat
      brain.
AB  - The novel antiepileptic and neuroprotective drug felbamate (1 mM) caused a marked
      inhibition of voltage-dependent Na+ currents expressed in Xenopus oocytes upon
      injection of the cRNA encoding alpha-subunits from rat and human brain. This
      inhibition was present only if felbamate was perfused on the intracellular side
      of the membrane. In addition, felbamate seems to preferentially bind to and
      stabilize the inactivated state of the channel, resembling the action of local
      anesthetics. This study provides an additional mechanism by which felbamate might
      exert its wide-spectrum anticonvulsant and neuroprotective action.

PMID- 8982711
TI  - A genetic mouse model of helplessness sensitive to imipramine.
AB  - Lines of mice were selectively bred to diverge in their spontaneous helplessness
      in the tail suspension test. By the second generation of selection, only mice of
      the helpless line were sensitive to the antidepressant imipramine. Genetic
      factors substantially contribute to the susceptibility to helplessness in this
      mouse model. These selectively bred lines may represent potentially useful animal
      models to investigate behavioural, neurochemical and neuroendocrine correlates of
      antidepressant action.

PMID- 8982712
TI  - Effects of the kappa-opioid receptor agonist U-50,488 on morphine-induced place
      preference conditioning in the developing rat.
AB  - The ability of the kappa-opioid receptor agonist trans-(+/-)- 3,4-dichloro-N
      methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methanesulfonate (U
      50,488) to modulate morphine-induced reward was assessed in preweanling (10- and
      17-day-old) and periadolescent (35-day-old) rats using the conditioned place
      preference paradigm. Conditioning and testing were conducted in a three
      compartment chamber, with each end compartment having its own distinct tactile
      and odor cues (almond or lemon). An abbreviated conditioned place preference
      procedure was used in which rats received two saline-odor pairings on the first
      conditioning day, and two saline- or morphine-odor pairings on the second day. In
      some experiments, rats were given U-50,488 (2-10 mg/kg, s.c.) 30 min prior to
      being conditioned with morphine (0.1-8 mg/kg, i.p.). On the third day, rats were
      allowed free access to the entire chamber for 900 s and compartment preferences
      were determined. Similar to adult rats, morphine (0.5 mg/kg) was consistently
      able to induce conditioned place preferences in the two preweanling age groups.
      This effect was attenuated by kappa-opioid receptor agonist pretreatment, as U
      50,488 not only enhanced the locomotor activity of 10- and 17-day-old rats, but
      it blocked the morphine-induced place preference conditioning of these younger
      animals. In contrast, periadolescent (35-day-old) rats did not exhibit morphine
      induced place preferences, nor did they show enhanced locomotor activity after U
      50,488 treatment; however, using the same procedure, a different group of
      similarly aged rats showed conditioned preference produced by 20 mg/kg cocaine
      (i.p.). Therefore, these results suggest that reward processes are functionally
      mature in the preweanling rat (at least by 10 days of age), but that
      periadolescent rats are generally unresponsive to mu- and kappa-opioid drugs.

PMID- 8982713
TI  - Nociceptin stimulates locomotion and exploratory behaviour in mice.
AB  - The recently characterized heptadecapeptide nociceptin, the endogenous agonist of
      the orphan opioid receptor-like 1 (ORL1 receptor), has been tested for its
      effects on locomotion and exploratory behaviour in mice. I.c.v. administration of
      as little as 10 ng of nociceptin/animal stimulated locomotor activity. This
      effect was dose-dependent, increasing in intensity up to 100 ng and in duration
      for doses in the range of 1000-10000 ng. The stimulation of horizontal locomotion
      elicited by 100 ng nociceptin was accompanied by a stimulation of the vertical
      component of locomotion. These effects were not reversed by high doses (1.5 and
      4.5 mg/kg s.c.) of the opioid receptor antagonist naloxone. Increasing doses of
      the dopamine D2 receptor antagonist haloperidol (0.1-0.5 mg/kg i.p.) as well as
      of the dopamine D1 receptor antagonist SCH 23390 [R(+)-7-chloro-8-hydroxy-3
      methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride] (0.0075-0.03
      mg/kg s.c.) reversed this effect, suggesting that nociceptin exerts its motor
      stimulant actions by increasing central dopaminergic transmission. Nociceptin was
      also found to increase the number of head dips in the hole-board test, indicating
      that the peptide stimulates exploratory behaviour.

PMID- 8982714
TI  - Ro 15-4513 potentiates, instead of antagonizes, ethanol-induced sleep in mice
      exposed to small platform stress.
AB  - The effects of ethanol and the benzodiazepine receptor ligand ethyl-8-azido-5,6
      dihydro-5-methyl-6-oxo-4H-imidazo-[1,5a] [1,4] benzodiazepine-3-carboxylate (Ro
      15-4513), were examined in NMRI mice exposed to small platform stress. This model
      contains several factors of stress, like rapid eye movement (REM) sleep
      deprivation, isolation, immobilization, falling into water and soaking. In
      control mice, ethanol exerted an anxiolytic effect in the plus-maze, but did not
      further enhance the anxiolytic-like effects induced by small platform stress. Ro
      15-4513 antagonized ethanol-induced sleep in control animals, but enhanced the
      hypnotic and lethal actions of ethanol in small platform stressed mice. Small
      platform stress did not alter the characteristics (KD and Bmax) of [3H]Ro 15-4513
      binding to cerebellar membranes. Muscimol-stimulated 36Cl- uptake into brain
      microsacs was significantly reduced in cortex from small platform stressed
      animals. Ethanol had no effect on 36Cl- uptake into brain microsacs from cortex
      or cerebellum. It is proposed that small platform stress alters the activity of
      the gamma-aminobutyric acid (GABA)A receptor-chloride ionophore complex, causing
      changes in the interaction between ethanol and Ro 15-4513.

PMID- 8982715
TI  - 8-OH-DPAT-induced mydriasis in mice: a pharmacological characterisation.
AB  - 8-Hydroxy(di-n-propylamino)tetralin (8-OH-DPAT; 0.1-50 mg/kg i.p.) evoked a dose
      dependent mydriatic response in conscious mice (ED50 = 5.8 mg/kg i.p.) which was
      maximal after 10 min. 8-OH-DPAT (2 mg/kg i.p.)-induced mydriasis was attenuated
      by the alpha 2-adrenoceptor antagonists, idazoxan (1 and 3 mg/kg i.p.) and
      yohimbine (1 and 3 mg/kg i.p.), by the 5-HT1 receptor antagonists, pindolol (10
      mg/kg i.p.) and quipazine (2 mg/kg i.p.), and by the selective 5-HT1A receptor
      antagonist, (-)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenyl
      propionamide ((-)-WAY 100135; 1-10 mg/kg s.c.). These data argue that both
      central alpha 2-adrenoceptors and 5-HT1A receptors are involved in the mediation
      of mydriasis induced by 8-OH-DPAT. The synaptic location of these receptors was
      determined using either N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 100
      mg/kg i.p.) or 5,7-dihydroxytryptamine (5,7-DHT; 75 micrograms i.c.v.)+p
      chlorophenylalanine (PCPA; 200 mg/kg i.p.); these lesioning procedures
      respectively produced highly significant losses of whole brain noradrenaline (72%
      depletion) and 5-HT (78% depletion). The former abolished 8-OH-DPAT (5 mg/kg i.p.
      (ED50)) mydriasis, whereas the latter was without effect. 8-OH-DPAT (0.5-5 mg/kg
      i.p.) also dose-dependently increased the noradrenaline metabolite, 3-methoxy-4
      hydroxy-phenylglycol (MHPG), in mouse whole brain minus cerebellum. Taken
      together these results show that 8-OH-DPAT initially stimulates 5-HT1A receptors,
      and it is likely that this is followed by release of noradrenaline onto
      postsynaptic alpha 2-adrenoceptors, the latter effect being responsible for the
      mydriatic response.

PMID- 8982716
TI  - Pharmacology of U-91356A, an agonist for the dopamine D2 receptor subtype.
AB  - U-91356A [(R)-5,6-dihydro-5-(propylamino)4H-imidazo[4,5,1-ij]quinolin -2-(1H)
      one, monohydrochloride], bound with highest affinity to the dopamine D2 receptor
      subtype, although it also bound with somewhat lower affinities to the dopamine D3
      and D4, as well as the 5-HT1A receptor subtypes. In addition to depressing
      dopamine synthesis and turnover, injection of U-91356A increased striatal
      acetylcholine concentrations. U-91356A also depressed firing rates of dopamine
      neurons. In mice, this compound stimulated cage climbing and locomotor activity
      in reserpinized animals; it also antagonized D-amphetamine-stimulated locomotor
      activity. It produced contralateral turning in rats with unilateral lesions of
      the substantia nigra. These data are consistent with roles for the dopamine D2
      receptor subtype as a dopamine autoreceptor and as a stimulatory, postsynaptic
      dopamine receptor.

PMID- 8982717
TI  - The anti-craving drug acamprosate reduces c-fos expression in rats undergoing
      ethanol withdrawal.
AB  - Acamprosate (Ca salt of N-acetylhomotaurine) is a novel anti-craving substance
      which a double-blind placebo-controlled study has proven to be therapeutically
      useful in the prevention of relapses in weaned alcoholics. In the present study
      the expression of the immediate-early gene c-fos in rat hippocampal and
      cerebellar neurons was used to monitor the modulatory effect of acamprosate on
      neuronal excitability during ethanol withdrawal. Several hybridization techniques
      were employed to investigate the effect of acamprosate on c-fos expression.
      Acamprosate (200 mg/kg; intraperitoneally) reduced the elevated c-fos mRNA levels
      in the hippocampus and the cerebellum following 24 h of ethanol withdrawal, or
      the application of the convulsant pentylenetetrazole. The effect of ethanol
      withdrawal on c-fos expression was more pronounced in the cerebellum than in the
      hippocampus. In the hippocampus (CA1) and the cerebellum acamprosate alone
      induced a significant increase in c-fos expression in drug-naive animals. Only in
      the hippocampus did co-administration of pentylenetetrazole during ethanol
      withdrawal induce a further increase in c-fos expression. The present findings
      support the notion that acamprosate elicits its preventive effect on relapse by
      reducing the hyperexcitability of central neurons during withdrawal, following
      long-term ethanol consumption.

PMID- 8982718
TI  - 5-HT1A receptor agonist effects of BMY-14802 on serotonin release in dorsal raphe
      and hippocampus.
AB  - BMY-14802 (BMS-181100; alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1
      piperazine butanol monohydrochloride) is a sigma receptor antagonist with
      potential antipsychotic activity. BMY-14802 also binds to 5-HT1A receptors and is
      able to inhibit the firing of dorsal raphe serotonergic neurons, suggesting that
      this compound has 5-HT1A receptor agonist properties in vivo. In the present
      study, we used in vivo microdialysis to study the effects of BMY-14802 on
      extracellular serotonin (5-hydroxytryptamine), 5-hydroxyindole-3-acetic acid (5
      HIAA) and homovanillic acid (HVA) in the dorsal raphe and ventral hippocampus in
      the awake rat. Systemic injections of 5-20 mg/kg BMY-14802 induced a simultaneous
      dose-dependent decrease in 5-HT and markedly increased the dopamine metabolite,
      HVA concentrations in dialysates from dorsal raphe and hippocampus. Extracellular
      concentrations of the 5-HT metabolite, 5-HIAA decreased only after 20 mg/kg BMY
      14802. The 5-HT decreases in dorsal raphe and hippocampus produced by BMY-14802
      were completely antagonized by pretreatment with 1.0 mg/kg of the specific 5-HT1A
      antagonist, WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridinyl) cyclohexanecarboxamide trihydrochloride). These data indicate that BMY
      14802 decreases dorsal raphe and hippocampal release of 5-HT by interaction with
      somatodendritic 5-HT1A receptors in the raphe nuclei and suggest that this
      compound is a potential anxiolytic.

PMID- 8982719
TI  - Turnover rate and stimulus-evoked release of dopamine by progesterone and N
      methyl-D-aspartic acid in rat striatum during pregnancy.
AB  - The proposed modulatory role of progesterone on dopaminergic nerve terminal
      activity in the striatum was examined in pregnant rats. Endogenous dopamine
      concentration and the in vitro effect of exogenous progesterone in association
      with N-methyl-D-aspartic acid (NMDA) upon [3H]dopamine release from striatal
      slices were determined. Striatal dopamine and 3,4-dihidroxyphenylacetic acid
      (Dopac) contents on day 5 of pregnancy were significantly higher than those found
      at the other stages of pregnancy and proestrus. On days 5 and 15 of pregnancy,
      progesterone (400 nM) was able to enhance [3H]dopamine release stimulated by NMDA
      (50 microM). A similar effect was found in striatal slices from proestrus rats.
      In contrast, progesterone was without an effect on days 1, 10 and 20 of pregnancy
      and postpartum. The results suggest that an increased synthesis and/or release of
      dopamine takes place on certain days of pregnancy and, simultaneously, that there
      is a significant increase in the responsiveness of striatal dopaminergic nerve
      terminals to excitatory inputs. They provide further support for a modulatory
      role of progesterone in relation with a glutamatergic action on dopaminergic
      activity in the corpus striatum.

PMID- 8982720
TI  - Nitric oxide mediates central activation of sympathetic outflow induced by
      interleukin-1 beta in rats.
AB  - The excitatory mechanism of central sympathetic outflow induced by interleukin-1
      beta was investigated in urethane-anesthetized rats. Intracerebroventricular
      administration of interleukin-1 beta induced a gradually developing elevation of
      plasma noradrenaline levels in a dose-dependent manner (50, 100 and 200
      ng/animal), while the levels of adrenaline were not affected. The elevation of
      noradrenaline levels induced by interleukin-1 beta (100 ng/animal i.c.v.) was
      abolished by the following treatments with: (1) a chemical sympathectomizer, 6
      hydroxydopamine (15 mg/kg i.v., 3 days before); (2) a prostaglandin synthesis
      inhibitor, indomethacin (500 micrograms/animal i.c.v.); (3) a nitric oxide
      synthase inhibitor, L-NG-nitroarginine methyl ester (100 micrograms plus 10
      micrograms/min i.c.v.); and (4) a nitric oxide scavenger, oxyhemoglobin (32.3
      micrograms plus 3.23 micrograms/min i.c.v.). In contrast to these results, D-NG
      nitroarginine methyl ester, an inactive isomer of L-NG-nitroarginine methyl
      ester, and methemoglobin, a metabolite of oxyhemoglobin, were without effect.
      Furthermore, prostaglandin E2 (100 ng/animal i.c.v.) rapidly and markedly
      elevated the plasma level of noradrenaline but not adrenaline. This prostaglandin
      E2-induced elevation of plasma noradrenaline levels was not attenuated by L-NG
      nitroarginine methyl ester (100 micrograms plus 10 micrograms/min i.c.v.). The
      present results suggest that nitric oxide is involved in the interleukin-1 beta
      induced central activation of sympathetic outflow. Furthermore, there probably
      exists nitric oxide-linked prostaglandin-generating system in the brain.

PMID- 8982721
TI  - Evaluation in rat of RS-79948-197 as a potential PET ligand for central alpha 2
      adrenoceptors.
AB  - Tritium-labelled RS-79948-197 {(8aR,12aS,13aS)-5, 8,8a,9,10,11,12,12a,13,13a
      decahydro-3-methoxy-12-(ethylsulphon yl)-6H-iso- quino[2,1-g][1,6]naphthyridine}
      was evaluated in rat brain as an in vivo ligand for central alpha 2
      adrenoceptors, as a preliminary step in the development of a radioligand for
      positron-emission tomography (PET) studies. The maximal receptor-specific signal
      was achieved within 90-120 min after i.v. injection of [ethyl-3H]RS-79948-197 and
      was selective for the alpha 2- compared with the alpha 1-adrenoceptor, with no
      detectable binding to the imidazoline-I2 site. Estimates for binding potential
      (approximating to Bmax/Kd) ranged between 3.4 in entorhinal cortex and 0.5 in
      medulla oblongata. The results, which indicate a similarly localised but 2-fold
      increase in specific binding compared with that previously demonstrated using
      [3H]RX 821002 (2-methoxy-idazoxan), are sufficiently encouraging as to support
      further investment in the development of 11C-labelled RS-79948-197, or a close
      structural analogue, as a ligand for clinical PET.

PMID- 8982722
TI  - Central antinociceptive effects of mitragynine in mice: contribution of
      descending noradrenergic and serotonergic systems.
AB  - Mitragynine is a major alkaloidal constituent of young leaves of Mitragyna
      speciosa Korth, that is known to exhibit narcotic-like activity. In this study,
      we investigated the roles of central monoaminergic systems in the antinociceptive
      action of mitragynine by means of the tail-pinch and hot-plate tests in mice.
      Mitragynine (1.0-10 micrograms) injected i.c.v. exerted a dose-dependent
      antinociceptive activity in both tests. The activity of mitragynine (10
      micrograms, i.c.v.) in the tail-pinch test was antagonized by reserpine, 6
      hydroxydopamine plus nomifensine, and p-chlorophenylalnine treatment, whereas the
      antinociceptive activity of morphine (3 micrograms) given i.c.v. in this test was
      attenuated by 6-hydroxydopamine plus nomifensine but not by p-chlorophenylalanine
      treatment. Moreover, the activity of i.c.v. mitragynine was also antagonized by
      the alpha 2-adrenoceptor antagonist, idazoxan (10 micrograms), and cyproheptadine
      (1 microgram) administered intrathecally (i.t.). On the other hand, the
      antinociceptive action of i.c.v. mitragynine (10 micrograms) in the hot-plate
      test was abolished by reserpine and 6-hydroxydopamine plus nomifensine, but not
      by p-chlorophenylalanine treatment. This action was also antagonized by i.t.
      injection of idazoxan (10 micrograms). These results suggest that both descending
      noradrenergic and serotonergic systems are involved in the antinociceptive
      activity of supraspinally administered mitragynine on the mechanical noxious
      stimulation, while the descending noradrenergic system predominantly contributes
      to the effect of supraspinal mitragynine on the thermal noxious stimulation. The
      mechanisms underlying the suppressive action of mitragynine on the nociceptive
      response may differ from those of morphine in mice.

PMID- 8982723
TI  - Increased noradrenaline efflux induced by local infusion of fluoxetine in the rat
      frontal cortex.
AB  - In microdialysis experiments in vivo, local infusion of either the selective
      serotonin reuptake inhibitor, fluoxetine, or the selective noradrenaline uptake
      inhibitor, desipramine, increased noradrenaline efflux in rat frontal cortex.
      Synaptosomal uptake of [3H]noradrenaline was used to test whether inhibition of
      uptake could contribute to this effect of fluoxetine. Low concentrations of
      fluoxetine were less effective than desipramine at inhibiting [3H]noradrenaline
      uptake; both compounds were more potent than the selective serotonin reuptake
      inhibitor, citalopram. To investigate whether this inhibition of uptake involved
      an action on noradrenergic neurones, experiments compared the effects of a
      noradrenergic lesion, induced by the neurotoxin N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP-4), on the inhibition of uptake by fluoxetine, desipramine
      and citalopram. The lesion reduced [3H]noradrenaline uptake in the presence of
      fluoxetine and citalopram but increased it in the presence of desipramine. The
      results suggest both that inhibition of noradrenaline uptake could contribute to
      the actions of fluoxetine and that a non-noradrenergic mechanisms is a target for
      this action.

PMID- 8982724
TI  - Characterization of thromboxane A2/prostaglandin endoperoxide receptors in aorta.
AB  - Thromboxane A2/prostaglandin endoperoxide receptor antagonists were studied in
      rat and guinea-pig aortas contracted with U-46619 (9,11-dideoxy-11 alpha,9 alpha
      epoxymethanoprostaglandin F2 alpha) or 8-epi-prostaglandin F2 alpha. In rat
      aorta, the antagonists competitively inhibited contractions evoked by either
      agonist with a rank order of potency as follows: BMS-180291 ([1s-(exo,exo)]-2-[[3
      [4-[(pentylamino) carbonyl]-2-oxazolyl]-7-oxabicyclo[2.2.1]hept-2-yl]methyl]-benz
      enepropanoic acid) > or = SQ 29,548 ([1s-[1 alpha,2 beta-(5z), 3 beta,4 alpha)]-7
      [3-[[2-[(phenylamino)carbonyl]hydrozino] methyl]-7-oxobicyclo-[2.2.1]hept-2-yl]-5
      heptanoic acid) > daltroban (4-[2-(4-chlorobenzenesulfonylamino) methyl]-benzene
      acetic acid) > or = SQ 30,741 ([1s-[1 beta,2 alpha(5z),3 alpha,4 beta]]-7-[3
      [[[[(oxa)amino]acetyl] amino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl-5-heptanoic
      acid) = AA-2414 (2,4,5-trimethyl-3,6-dioxo-zeta-phenyl-1,4-cyclohexadien-1
      heptano ic acid). In guinea-pig aorta, the antagonists competitively antagonized
      contractions elicited by either agonist with the following rank order of potency:
      SQ 29,548 = AA-2414 > or = SQ 30,741 > daltroban. Antagonism by BMS-180291 in
      guinea-pig aorta was not strictly competitive. These findings indicate that
      thromboxane A2/prostaglandin endoperoxide receptors in rat aortas are different
      from those in guinea pigs. Because the actions of both agonists were equivalently
      antagonized by each of the antagonists in both rat and guinea-pig aortas, the
      results do not support the hypothesis that U-46619 and 8-epi-prostaglandin F2
      alpha elicit contractions via different receptor subtypes in the aorta.

PMID- 8982725
TI  - Influence of purines and pyrimidines on circular muscle of the rat proximal
      stomach.
AB  - The effects of UTP were examined to characterize the receptor subtypes for UTP in
      the circular smooth muscle of the rat proximal stomach. The rank order of potency
      for contraction was 2-methylthio ATP > > ATP > or = UDP = UTP > or = adenosine 5'
      O-(3-thiotriphosphate) (ATP-gamma-S) > > UMP > CTP = alpha,beta-methylene ATP >
      adenosine = uridine. In tissues contracted by acetylcholine, ATP, 2-methylthio
      ATP, alpha,beta-methylene ATP and adenosine each caused relaxation. alpha,beta
      Methylene ATP had the most potent effect and UTP caused only a small relaxation.
      Suramin inhibited ATP- and UTP-induced contractions. The contractile responses to
      ATP decreased in tissues desensitized with UTP, ATP-gamma-S and 2-methylthio ATP,
      but not with alpha,beta-methylene ATP. However, UTP-induced contraction was not
      inhibited by desensitization with ATP, alpha,beta-methylene ATP, ATP-gamma-S and
      2-methylthio ATP. These results suggest that UTP causes contraction via receptors
      different from common P2 purinoceptors. These receptors are blocked by suramin in
      the rat proximal stomach.

PMID- 8982726
TI  - The cysteinyl-leukotriene receptor antagonist BAY u9773 is a competitive
      antagonist of leukotriene C4 in the guinea-pig ileum.
AB  - Two main classes of receptors exist for leukotrienes C4, D4 and E4, collectively
      named cysteinyl-leukotrienes (CysLTs). The CysLT1 receptor is blocked by
      currently available leukotriene antagonists, and the CysLT2 receptor is defined
      by the absence of selective antagonists. The contractile response to leukotriene
      C4 in guinea-pig ileum longitudinal muscle is resistant to CysLT1 receptor
      antagonists. However, the leukotriene E4 analogue BAY u9773 (6(R)-(4'
      carboxyphenylthio)-5(S)-hydroxy-7(E),9(E),11(Z), 14(Z)-eicosatetraenoic acid) has
      recently been reported to inhibit CysLT2 responses. Therefore BAY u9773 was
      evaluated for antagonism of the effect of leukotriene C4 in the guinea-pig ileum
      longitudinal muscle. We found that BAY u9773 (0.3-10 microM) did not contract the
      preparation, but produced a concentration-dependent rightward shift in the
      concentration-response relation for leukotriene C4. Schild plot analysis yielded
      a slope which was not significantly different from unity and a pA2 value of 6.1.
      The inhibition of leukotriene C4 by BAY u9773 was not altered by antagonism of
      CysLT1 receptors by ICI 198,615 {[1-[[2-methoxy-4
      [[(phenylsulfonyl)amino]carbonyl]-phenyl] methyl]-1H-indazol-6-yl]carbamic acid
      cyclopentyl ester}(100 nM). The CysLT1 receptor agonist, leukotriene E4 (1
      microM), contracted the preparation but did not inhibit the contraction induced
      by leukotriene C4. Taken together, the antagonism exerted by BAY u9773 appeared
      unrelated to actions on CysLT1 receptors. In conclusion, BAY u9773 was a useful
      selective competitive antagonist of leukotriene C4, and the findings support the
      classification of the receptors for leukotriene C4 in the guinea-pig ileum as
      CysLT2.

PMID- 8982727
TI  - A mechanistic study of beta-adrenoceptor antagonists on ethanol-induced gastric
      damage.
AB  - The beta-adrenoceptor subtypes and the roles of myeloperoxidase and prostaglandin
      E2 in the anti-ulcer effect of beta-adrenoceptor antagonists were studied. A non
      selective beta-adrenoceptor antagonist, propranolol, or selective beta
      adrenoceptor antagonists, metoprolol (a beta 1-adrenoceptor antagonist) or
      butoxamine (a beta 2-adrenoceptor antagonist) were used. Propranolol given either
      intraperitoneally or orally reduced ethanol-induced mucosal damage and
      myeloperoxidase activity. Oral administration of butoxamine produced similar
      effects. The blood neutrophil count was increased after ethanol administration
      and this was reversed by the two drugs. Metoprolol did not affect myeloperoxidase
      activity, neutrophil count and mucosal damage under these experimental
      conditions. Oral administration of propranolol or butoxamine increased mucosal
      prostaglandin E2 level. It is concluded that the inflammatory responses to
      ethanol, as indicated by neutrophil infiltration in gastric mucosa, can be
      specifically inhibited by drugs that block beta 2-adrenoceptors. This action
      would explain in part why propranolol and butoxamine but not metoprolol lessened
      gastric damage. In addition, oral administration of propranolol and butoxamine
      increased the mucosal prostaglandin E2 level, which could partially contribute to
      their anti-ulcer effects.

PMID- 8982729
TI  - L-733,060, a novel tachykinin NK1 receptor antagonist; effects in [Ca2+]i
      mobilisation, cardiovascular and dural extravasation assays.
AB  - This study investigated the properties of a novel piperidine ether-based
      tachykinin NK1 receptor antagonist L-733,060, ((2S,3S)-3-((3,5
      bis(trifluoromethyl)phenyl)methyloxy)-2-phenyl piperidine and its 2R,3R
      enantiomer L-733,061 on [Ca2+]i mobilisation in Chinese hamster ovary cells
      transfected with human tachykinin NK1 receptors, compared to their effects in
      rodent cardiovascular and neurogenic plasma extravasation assays. Using FURA-2
      imaging techniques, L-733,060 inhibited substance P-induced [Ca2+]i mobilisation
      with an estimated affinity of 0.8 nM whereas L-733,061 (30-300 nM) did not. No
      significant effects of L-733,060 were observed on mean arterial blood pressure or
      heart rate in conscious or anaesthetised rats at doses of < 3000 micrograms kg-1
      i.v. L-733,060 also stereoselectively inhibited neurogenic plasma extravasation
      in rat dura produced by electrical stimulation of trigeminal nerves with an ID50
      of 212 +/- 19 micrograms kg-1 i.v. Thus, L-733,060 is a novel antagonist of human
      tachykinin NK1 receptors which stereoselectively inhibits neurogenic plasma
      extravasation at doses that do not cause adverse cardiovascular effects.

PMID- 8982728
TI  - In vivo effect of OPC15161, a superoxide scavenger, on anti-Thy1 nephritis.
AB  - The in vivo effect of 6-(1 H-indol-3-ylmethyl)-5-methoxy-3-(2-methylpropyl)-2(1
      H)-pyrazinone, 4-oxide (OPC15161), a superoxide scavenger, was studied in rats
      with anti-Thy1 nephritis. Rats were divided into 4 groups: G-1, normal control; G
      2, anti-Thy1 nephritis; G-3 anti-Thy1 nephritis and treated with OPC15161 (50
      mg/kg/day) starting at day 0; and G-4, anti-Thy1 nephritis and treated with
      OPC15161 starting 3 days before antibody injection. At weeks 2 and 8, rats were
      killed for morphological study and at week 8 for renal clearance. Results were
      compared among the 4 groups. OPC15161 suppressed urinary albumin/day. Total
      glomerular cells, mesangial cells, ED-1-positive cells/glomerulus and glomerular
      volume all increased and the increases were suppressed by OPC15161.
      Tubulointerstitial index, assessed by point counting, was improved by OPC15161 (P
      < 0.05 G-3, 4, vs. G-2, not significant vs. G-1). Glomerular filtration rate
      decreased in all nephritic animals, but the decrease in renal blood flow was less
      in the treated groups. These findings indicate a favorable effect of OPC15161 on
      the glomerular and interstitial lesions of anti-Thy1 nephritis.

PMID- 8982731
TI  - Induction of cyclooxygenase and nitric oxide synthase in endotoxin-activated J774
      macrophages is differentially regulated by indomethacin: enhanced cyclooxygenase
      2 protein expression but reduction of inducible nitric oxide synthase.
AB  - The involvement of prostaglandins in feedback modulation of the
      lipopolysaccharide-inducible isoforms of cyclooxygenase and nitric oxide was
      studied. This was done by testing the effects of arachidonic acid and
      indomethacin in the murine macrophage cell line J774. When added before
      lipopolysaccharide, arachidonic acid (10(-6)-10(-4) M) dose-dependently reduced
      inducible nitric oxide synthase and cyclooxygenase-2 activity as well as reducing
      the expression of both enzyme proteins. Indomethacin (10(-7)-10(-4) M) suppressed
      prostaglandin E2 release into the medium and reduced cyclooxygenase-2 activity
      irreversibly, as expected, but the amount of cyclooxygenase-2 protein was
      increased (because indomethacin removes the inhibitory effect of prostaglandins
      on cyclooxygenase-2 expression). However, the same doses of indomethacin also
      inhibited the release of nitric oxide into the medium. This was accompanied by a
      reduction in the amount of inducible nitric oxide synthase protein. The drug was
      not cytotoxic. Thus these results show that pharmacological treatments can have
      opposing actions on inducible nitric oxide synthase and cyclooxygenase-2
      induction, with indomethacin showing an additional unexpected action in
      macrophages which may diminish their cytotoxic potential.

PMID- 8982730
TI  - Nitric oxide donors induce apoptosis in glomerular mesangial cells, epithelial
      cells and endothelial cells.
AB  - Renal mesangial cells exposed to inflammatory cytokines produce high
      concentrations of nitric oxide (NO) which may exert cytotoxic actions. We report
      here that glomerular mesangial cells, endothelial cells and epithelial cells in
      culture are themselves targets for NO and undergo apoptotic cell death upon
      exposure to high concentrations of NO. NO generated from different NO-releasing
      compounds as well as NO-saturated solution induce apoptosis in all three cell
      types as demonstrated by internucleosomal DNA fragmentation, an enrichment of
      cytosolic DNA/histone complexes, an increasing number of cellular 3'-OH
      fragmented DNA ends and typical nuclear chromatin condensation. Induction of
      apoptosis was found to be dependent on protein synthesis and is preceded by
      expression of the tumour suppressor gene product p53 in mesangial cells.
      Induction of inducible NO synthase in mesangial cells by interleukin-1 beta leads
      to excessive formation of NO by the cells as measured by nitrite production.
      However, there was no evidence for apoptotic changes in mesangial cells triggered
      by endogenously produced NO. Co-cultures of glomerular endothelial or epithelial
      cells with interleukin-1 beta-activated mesangial cells expressing inducible NO
      synthase do not show apoptotic alterations in endothelial or epithelial cells.
      Moreover, preincubation of mesangial cells with interleukin-1 beta protects the
      cells from apoptosis induced by subsequent addition of exogenous NO thus
      suggesting that interleukin-1 beta not only triggers the expression of inducible
      NO synthase and massive NO formation but simultaneously stimulates a protecting
      principle in the cells. In summary, these results suggest that exogenous NO can
      induce apoptosis in all three types of intrinsic glomerular cells. However,
      whether endogenously produced NO can fulfil this function critically depends on a
      balance between a yet to be defined protective mechanism and inducible NO
      synthase expression in mesangial cells in response to interleukin-1 beta and
      eventually other inflammatory cytokines.

PMID- 8982732
TI  - Flupirtine increases the levels of glutathione and Bc1-2 in hNT (human Ntera/D1)
      neurons: mode of action of the drug-mediated anti-apoptotic effect.
AB  - Flupirtine is a triaminopyridine analogue which has been successfully applied in
      clinics as a non-opiate analgesic drug. Previously we described that flupirtine
      acts like an N-methyl-D-aspartate (NMDA) receptor antagonist in neuronal cells
      both in vitro and in vivo. Here we show that flupirtine displays its anti
      apoptotic effect also in hNT (human Ntera/D1) neurons. hNT neurons were induced
      to apoptosis applying glutamate (Glu; at concentrations > or = 1 mM) or NMDA (>
      or = 1 mM). During Glu/NMDA-mediated apoptosis the levels of the intracellular
      anti-apoptotic agents Bc1-2 and glutathione dropped by more than 50%. Flupirtine
      completely abolished this reduction of Bc1-2 and glutathione level at a
      concentration of 10 microM. In the presence of 3 microM flupirtine a > 6-fold
      increase of the Bc1-2 (B-cell leukemia/lymphoma-2) level was observed in hNT
      neurons. At the same concentration, the intracellular level of glutathione
      increased to 200%. We conclude that the Glu/NMDA-mediated neuronal cell death in
      vitro is controlled at least partially by Bc1-2 and glutathione. Neuronal cell
      death by Glu or NMDA in vitro can be overcome applying the drug flupirtine which
      is in clinical use.

PMID- 8982733
TI  - Modulation of membrane currents and mechanical activity by niflumic acid in rat
      vascular smooth muscle.
AB  - The effects of niflumic acid on whole-cell membrane currents and mechanical
      activity were examined in the rat portal vein. In freshly dispersed portal vein
      cells clamped at -60 mV in caesium (Cs+)-containing solutions, niflumic acid (1
      100 microM) inhibited calcium (Ca2+)-activated chloride currents (IC1(Ca))
      induced by caffeine (10 mM) and by noradrenaline (10 microM). In a potassium (K+)
      containing solution and at a holding potential of - 10 mV, niflumic acid (10-100
      microM) induced an outward K+ current (IK(ATP)) which was sensitive to
      glibenclamide (10-30 microM). At concentrations < 30 microM and at a holding
      potential of -2 mV, niflumic acid had no effect on the magnitude of the caffeine-
      or noradrenaline-stimulated current (IBK(Ca)) carried by the large conductance,
      Ca(2+)-sensitive K+ channel (BKCa). However, at a concentration of 100 microM,
      niflumic acid significantly inhibited IBK(Ca)) evoked by caffeine (10 mM) but not
      by NS1619 (1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl-2(3 H)
      benzimidazolone; 20 microM). In Cs(+)-containing solutions, niflumic acid (10-100
      microM) did not inhibit voltage-sensitive Ca2+ currents. In intact portal veins,
      niflumic acid (1-300 microM) inhibited spontaneous mechanical activity, an action
      which was partially antagonised by glibenclamide (1-10 microM), and contractions
      produced by noradrenaline (10 microM), an effect which was glibenclamide
      insensitive. It is concluded that inhibition of ICl(Ca) and stimulation of
      IK(ATP) both contribute to the mechano-inhibitory actions of niflumic acid in the
      rat portal vein.

PMID- 8982734
TI  - Leptin: genes, concepts and clinical perspective.
AB  - Obesity is a complex disease which results from the interaction of multiple genes
      and the environment. The recently discovered genes for leptin (ob gene) and the
      leptin receptor appear to play a major regulatory role in body energy balance and
      adipose tissue deposition. Furthermore, defects in the ob gene and leptin
      receptor gene have been demonstrated to be the cause of obesity in several rodent
      models. These observations raise the possibility that human obesity may also be
      due to defects in the leptin signal system. This review will summarize the
      current findings on the ob gene, leptin and the leptin receptor in both animals
      and humans. These observations will be discussed in the context of potential
      defects in the system and the possibility that these defects result in obesity in
      humans.

PMID- 8982735
TI  - Flow cytometry analysis of pituitary adenomas.
AB  - Using flow cytometry, DNA content and index, and/or proliferative capacity
      (measuring proliferating cell nuclear antigen PCNA) in operated pituitary tumors,
      control pituitaries obtained at necropsy, and experimental pituitary hyperplasia
      induced in rats were analyzed. Simultaneous measurement of cell ploidy and
      proliferation differentiated normal pituitary (diploid DNA index and negative
      PCNA) from pituitary hyperplasia (diploid DNA index with intensely positive PCNA,
      between 30 and 72% of cells). In the tumors 83% (19/ 23) were positive for PCNA
      (between 3 and 84%) and 73% (17/23) aneuploid; only 1 tumor was diploid and
      negative for PCNA. CONCLUSIONS: Differentiation between normal and abnormal
      (neoplastic or hyperplastic) pituitary is possible by flow cytometry, but in the
      adenomas no correlation with postoperative clinical outcome was observed.

PMID- 8982736
TI  - Changes in bone mineral density, growth velocity and renal function of
      prepubertal uremic children during growth hormone treatment.
AB  - Thirteen prepubertal children with a mean chronological age of 6.7 +/- 3.4 years
      and severe chronic renal failure (mean glomerular filtration rate of 20.8 +/-
      17.7 ml/min/1.73 m2) were studied. Patients received recombinant human growth
      hormone (rhGH) at a dose of 1 IU/kg/week given subcutaneously on a daily basis
      for 12 months. Mean growth rates of our patients increased significantly from a
      baseline level of 4.3 +/- 2.1 to 9.1 +/- 2.0 cm/year at 12 months of rhGH
      therapy. Mean height SDS improved from -3.5 +/- 1.0 at initiation of therapy to 
      2.6 +/- 1.3 at 12 months. Mean serum creatinine and blood urea nitrogen levels
      remained stable during the study, while mean glomerular filtration rates
      decreased initially and then stabilized; however, 2 subjects had a significant
      deterioration of their renal function at 6 and 9 months of rhGH, requiring
      discontinuing treatment. Before rhGH treatment, total bone mineral content as
      well as bone mineral density in cortical and trabecular bone were significantly
      reduced in our patients when compared to healthy controls paired for
      chronological age and similar to those of a healthy control group paired for bone
      age and height. Both these parameters increased significantly during rhGH
      treatment so that at 12 months our patients had values similar to those seen in a
      healthy control population paired to our patients for chronological age. While
      trabecular bone mineral density did not change in a group of untreated uremic
      controls during 12 months of follow-up, the percent of bone mineral density
      change in trabecular bone in our uremic patients during 12 months of rhGH
      treatment was very significant (p < 0.001) and larger than that noted in a group
      of healthy controls paired for bone age and height during 12 months of follow-up.
      This study demonstrates how rhGH treatment in prepubertal uremic children
      increases their growth velocity and their bone mineral density significantly,
      with an improvement in height for age. Careful followup of the renal function of
      patients in needed as they improve their height and bone mineral status.

PMID- 8982737
TI  - Final height in Turner syndrome patients treated with growth hormone.
AB  - Growth hormone (GH), alone or in combination with anabolic steroids, seems to
      improve the growth rate in Turner syndrome, but to exert a less striking effect
      on the final height (FH). Reports on the FH usually lack a control group, and the
      GH effect is determined using the gain in centimeters over projected height. Out
      of a cohort of 32 Turner syndrome girls under recombinant human GH (rhGH) therapy
      (0.5 IU/kg/week during the 1st year and 1 IU/kg/week subsequently), 18 (treated
      for 3-6 years) attained FH. The mean chronological age at the first examination
      was 9.6 +/- (SD) 2.1 years and at the start of GH therapy 13.0 +/- 2.0 (range 8.8
      17.2) years. Eighteen untreated subjects matched for chronological age and
      karyotype served as control group. The FH as SDS according to Lyon and to
      unpublished Italian Turner syndrome girl standards was not significantly
      different as compared with pretreatment. In comparison with Italian cross
      sectional Turner syndrome standards (FH 142.5 +/- 7.0 cm), the FH of the control
      group was quite similar (142.2 +/- 4.9 cm), whereas the rhGH-treated group showed
      a FH of 147.6 +/- 7.3 cm with a mean increment of about 5 cm. The height gain
      during therapy (as delta height in SDS either according to Lyon or to Italian SDS
      standards) was compared for each girl with that of a matched girl of the control
      group during a comparable observation period. A significantly different delta
      height was observed in the treated versus control groups: 0.3 +/- 1.1 vs. -1.0 +/
      0.8 according to Lyon (p < 0.001) and 0.8 +/- 0.7 vs -0.3 +/- 0.5 according to
      Italian standards (p < 0.001). If we compared the FH with the projected height
      according to Lyon standards, the height gain (as delta height in cm) was
      significantly higher than in the untreated subjects (-1.1 +/- 4.8 vs. -6.2 +/-
      3.9 cm; p < 0.05). It seems worthwhile to undertake GH treatment in Turner
      syndrome girls who represent a very short stature population, even though the
      response is less significant than in classic GH deficiency and shows a striking
      variability, probably due to a sort of peripheral resistance.

PMID- 8982738
TI  - Urinary growth hormone excretion in children and adolescents with insulin
      dependent diabetes mellitus.
AB  - Urinary growth hormone (uGH) excretion was evaluated in 96 type-1 insulin
      dependent diabetic patients and 37 age-matched healthy subjects. The growth
      hormone concentration was measured by a solid-phase immunoradiometric assay on 3
      consecutive overnight urine collections. uGH excretion was comparable between
      diabetic patients and healthy subjects: 10.9 (0.1-34.8) vs. 9.1 (2.6-34.5)
      pg/min. In both groups uGH excretion was lower in prepubertal than in pubescent
      or pubertal individuals (diabetic patients, H = 29.7, p = 0.001; healthy
      subjects, H = 10.4, p = 0.006). In diabetic patients uGH excretion was related to
      beta 2-microglobulin excretion (r = 0.308; p = 0.005) and to urinary albumin
      excretion (r = 0.230; p = 0.02) but it was independent of HbA1c and overnight
      glycemic values. The coefficient of variation of uGH excretion was higher in
      diabetic patients with respect to healthy subjects: 50 (3-141) vs. 28(3-100)% (p
      = 0.002). Among diabetic patients it was greater in prepubertal than in pubescent
      or pubertal patients (H = 13.7; p = 0.002); in contrast, it was independent of
      pubertal stage in healthy individuals (H = 2.4; NS). The coefficient of variation
      of uGH was not related to HbA1c, the duration of diabetes, the coefficient of
      variation of urinary albumin excretion and the coefficient of variation of beta 2
      microglobulin excretion. In conclusion uGH excretion is comparable among diabetic
      patients and healthy subjects, but its day-to-day fluctuation is greater in the
      former than in the latter group. Renal function but not metabolic control can
      influence uGH excretion. The day-to-day fluctuation in uGH excretion is
      independent of metabolic control and renal function.

PMID- 8982740
TI  - Menstrual bleeding patterns in Chinese women using the Norplant subdermal
      implant.
AB  - An analysis of the menstrual diary records of 306 cases of Norplant users over 5
      years is reported. The results indicate that the disturbances of menstrual cycles
      during Norplant use were mainly caused by changes in the total number of vaginal
      bleeding days. Menstrual patterns were irregular and prolonged. Disturbances of
      the menstrual pattern were improved after 6-12 months of use, mainly showing a
      decrease in the number of spotting days. About 30-40% of users may regain their
      normal menstrual pattern after 1 year of use. There was a proportion of cases
      with an abnormal menstrual pattern throughout the 5 years of use, but the gross
      cumulative termination rate for menstrual problems was only 13.0%. Norplant users
      are susceptible to an increase in the number of spotting days and irregular
      bleeding. The main reason for termination of contraceptive use was prolonged
      bleeding for a long time. This is important information that should be provided
      in counselling potential Norplant acceptors, especially the changes in menstrual
      pattern. We also have a responsibility to try to find a treatment for prolonged
      bleeding.

PMID- 8982739
TI  - Clinical evaluation of the therapeutic effectiveness of ethinyl oestradiol and
      oestrone sulphate on prolonged bleeding in women using depot medroxyprogesterone
      acetate for contraception. World Health Organization, Special Programme of
      Research, Development and Research Training in Human Reproduction, Task Force on
      Long-acting Systemic Agents for Fertility Regulation.
AB  - A placebo-controlled randomized clinical trial was conducted in six centres to
      compare the effects of a 14 day treatment with either 50 micrograms ethinyl
      oestradiol daily or 2.5 mg oestrone sulphate daily, on depot medroxyprogesterone
      acetate (DMPA)-induced prolonged bleeding. Out of 1035 women admitted to the
      study, 278 requested treatment and were given ethinyl oestradiol (n = 90),
      oestrone sulphate (n = 91) or placebo (n = 97). Ethinyl oestradiol was successful
      in stopping the bleeding episode in 93% of cases, compared with oestrone sulphate
      and placebo which had success rates of 76 and 74% respectively. However, the
      relative advantage of ethinyl oestradiol was marginal, with an average reduction
      of 1 bleeding day and 3 spotting days compared with the other two groups.
      Immediately after treatment, women given ethinyl oestradiol had less bleeding but
      a more unpredictable pattern than the other two groups. In the long term, there
      were no differences between the bleeding patterns or the discontinuation rates
      for any reason in the three groups, and the most important single reason for
      discontinuation in those groups remained 'menstrual problems'. In summary, the
      study showed that treatment of DMPA-induced prolonged bleeding with ethinyl
      oestradiol had a limited short-term effect but no beneficial effect on the
      acceptability of DMPA as a contraceptive method. Treatment with oestrone sulphate
      was no different from placebo.

PMID- 8982741
TI  - Progestogen-only pills and bleeding disturbances.
AB  - The progestogen-only pill (POP), minipill, is quite an effective second line
      contraceptive. Despite this, it is used relatively infrequently except during
      lactation. The main reason for this is that women on POP often have abnormal
      bleeding patterns, with an increased frequency of bleeding, lengthened cycles,
      breakthrough bleeding, spotting and prolonged bleeding. These menstrual
      disturbances are the most common quoted reason for discontinuation in up to 25%
      of users.

PMID- 8982743
TI  - Endometrial biopsy collection from women receiving Norplant.
AB  - A series of 191 endometrial biopsy procedures were performed on Indonesian women
      who had received between 3 and 12 months exposure to Norplant. In all, 87 biopsy
      procedures were attempted with a microhysteroscope using biopsy forceps, and 104
      procedures were attempted with either Pipelle or Karman suction curettes.
      Regardless of the biopsy method, diagnosable endometrium was obtained in only
      approximately 50% of procedures. Myometrium was often found in microhysteroscope
      but not in suction biopsies. An analysis of a number of clinical characteristics
      showed that women from whom diagnosable endometrial tissue was obtained had
      higher mean peripheral oestrogen concentrations in the 2 weeks prior to biopsy
      (439 +/- 35 versus 289 +/- 33 pmol/l; P = 0.0018) and significantly more days
      when endometrial bleeding occurred in the 90 days prior to biopsy (26.5 +/- 2.1
      versus 16.2 +/- 1.8; P = 0.0003). These results suggest that after 3-12 months
      exposure to Norplant approximately 50% of women have an endometrium too thin to
      sample, and that this group is characterized by lower peripheral oestrogen
      concentrations and reduced menstrual bleeding.

PMID- 8982742
TI  - Management of irregular uterine bleeding and spotting associated with Norplant.
AB  - Norplant, a systemic contraceptive, has been used extensively throughout the
      world. A major problem for consumers utilizing Norplant has been irregular,
      unpredictable uterine bleeding or spotting. This study seeks to determine whether
      or not an appropriate treatment could be found that will reduce the incidence of
      spotting and bleeding. Both a pilot study and an interim report of a multi-center
      trial utilizing ethinyl estradiol 20 micrograms for 10 days, versus Ibuprofen 800
      mg three times a day for 5 days, versus placebo is reported. Based on the interim
      analysis of the multi-center trial, there is a reduction in the mean number of
      spotting days with one of the three treatments compared to the other two
      treatments (p = 0.044). There was no difference in the number of bleeding days
      between treatment regimen. It appears from a review of the literature that both
      oestrogen, progesterone, and non-steriodal anti-inflammatory agents may reduce
      the number of bleeding days or inhibit acutely the bleeding in women utilizing
      Norplant. The completion of this randomized multi-center trial will hopefully
      give us further insight into an effective treatment for controlling the irregular
      bleeding and/or spotting that occurs in Norplant users.

PMID- 8982744
TI  - Endometrial vasculature in Norplant users: preliminary results from a
      hysteroscopic study.
AB  - Long-acting progestogenic contraceptives are frequently associated with
      disturbances of menstrual bleeding patterns. In particular, irregular, frequent
      and prolonged bleeding are commonly seen. The mechanism of this irregular
      bleeding is unknown, but changes in the endometrial vasculature are thought to be
      of importance. In endometrial biopsies from Norplant users, an increase in
      endometrial microvascular density has been observed after 3-12 months.
      Morphological changes in endometrial capillaries following progestogen exposure
      have suggested an increase in vascular fragility. Little is known about the
      structure and function of the endometrial vasculature in vivo following exposure
      to exogenous contraceptive steroids. This study has developed techniques for the
      assessment of vascular fragility by imposing a mechanical stress on the
      endometrium and observing subsequent bleeding under direct vision. The techniques
      were used in a preliminary examination between 1 and 9 months after Norplant
      insertion, and the study identified a number of morphological and functional
      characteristics of Norplant-exposed endometrium.

PMID- 8982745
TI  - Endometrial vasculature in Norplant users.
AB  - Disrupted, prolonged and irregular endometrial bleeding are major unwanted side
      effects of progestin-only contraceptives. The aim of this paper is to review
      current information on steroid control of the microvasculature, microvascular
      heterogeneity and microvascular fragility, with emphasis on the relevance of
      these issues to the endometrial microvasculature in women receiving Norplant
      implant contraception. Subjects were either Indonesian women with between 3 and
      12 months exposure to Norplant (n = 191) or Caucasian controls recruited in
      Melbourne, Australia. Norplant endometrium was always thinner than control
      endometrium, with a varied histology that usually included a basalis-type
      appearance, signs of haemorrhage and some dilated and congested subepithelial
      vessels. Thin-walled vessels were seen which could have been either blood
      vascular or lymphatics. Steroid control of the vasculature can operate through
      numerous direct and indirect mechanisms, with up to 30 genes relevant to vascular
      function having consensus oestrogen response elements in their promoter regions.
      The vasoactive effects of progesterone are less well documented. However,
      experimental data for direct effects on the endometrial vasculature are mounting.
      Progestin-induced endometrial breakthrough bleeding is often focal, suggesting
      that microvascular heterogeneity may be an important factor in understanding this
      phenomenon. Increased susceptibility to bleeding may result from increased
      microvascular fragility, possibly as a consequence of progestins altering the
      balance of angiogenic promoters and inhibitors in the endometrium, thus leaving
      the vessels in a permanently weakened state.

PMID- 8982746
TI  - Endometrial angiogenic response in Norplant users.
AB  - The levonorgestrel-releasing subdermal contraceptive implant Norplant is well
      accepted among Indonesian users, despite the problems with irregular and
      prolonged menstrual bleeding. Bleeding can be the major reason for women
      discontinuing their use of Norplant. The causes of endometrial bleeding may
      include disturbances in endometrial regeneration and angiogenesis. The aim of
      this study was to investigate endometrial angiogenic activity in Norplant users
      and to compare it to that in the normal menstrual cycle. The study also aimed to
      determine the correlation between endometrial angiogenic activity and plasma
      concentrations of oestradiol, progesterone, sex hormone binding globulin and
      levonorgestrel, as well as the free levonorgestrel index. The subjects for this
      study were selected from Norplant users with an exposure of between 3 and 12
      months. Endometrial angiogenic response was assayed using an endothelial cell
      migration assay. Six blood samples to monitor oestradiol and progesterone
      concentrations were taken during the 2 weeks prior to endometrial biopsy. Samples
      for the analysis of sex hormone binding globulin and levonorgestrel were taken on
      the day of biopsy. The results showed that the median score of endometrial
      angiogenic activity in the 30 women used as controls were significantly higher
      than the 40 Norplant acceptors (z = -3.80, one tail, P < 0.001). There was no
      significant correlation between the endothelial migration score and peripheral
      hormonal concentrations or the free levonorgestrel index in Norplant users. There
      was no difference in the endometrial angiogenic activity in endometrium with and
      without bleeding problems. However, it is interesting to note that four Norplant
      acceptors who had an endothelial cell migration score > or = 1.0 had the lowest
      free levonorgestrel index.

PMID- 8982747
TI  - Vascular endothelial growth factor and the endometrium.

PMID- 8982748
TI  - The endothelin-parathyroid hormone-related protein vasoactive peptide system in
      human endometrium: modulation by transforming growth factor-beta.
AB  - Endothelin-1 (ET-1), a potent vasoconstrictor, and parathyroid hormone-related
      protein (PTH-rP), a potent vasorelaxant, are present and synthesized in human
      endometrium. The production of these vasoactive peptides in stromal cells of the
      human endometrium is modulated by sex steroid hormones. In addition, neutral
      endopeptidase 24.11 (also called enkephalinase), which degrades ET-1, is
      expressed in the stromal cells of the endometrium, and the levels of this enzyme
      (mRNA, protein and specific activity) are increased in response to
      progesterone/progestin. The sex steroid hormone-mediated regulation of vasoactive
      peptide formation and action in the human endometrium is believed to serve a key
      role in modulating spiral artery tone/blood flow, and thus endometrial bleeding,
      whether progestin induced or naturally occurring. Moreover, the expression of ET
      1, PTH-rP and enkephalinase is modulated by transforming growth factor-beta. We
      hypothesize that the inappropriate expression of ET-1, enkephalinase and PTH-rP
      in endometrial stromal cells during synthetic progestin administration may be one
      cause of abnormal endometrial development and erratic endometrial bleeding.

PMID- 8982749
TI  - Endothelin and menstruation.
AB  - Endothelin (ET) and its mRNA are present in human endometrium. Its expression
      varies across the menstrual cycle, reaching maximal levels in the pre-menstrual
      phase. Human endometrial epithelial cells are the major in-vitro source of ET,
      and its release is affected by the stage of the menstrual cycle from which the
      endometrium is taken and by the cytokines transforming growth factor-beta 1 and
      interleukin-1 alpha. The cyclical variation in both ET mRNA and protein
      expression across the normal menstrual cycle, and the differences observed in
      abnormal uterine bleeding (specifically reduced immuno-reactivity in luminal and
      glandular epithelium in the endometrium of Norplant users), are consistent with a
      role for ET in the control of menstrual bleeding. The role of epithelial cell ET
      is not yet understood. Whether this source of ET is important in endometrial
      regeneration and repair following menstruation or in vaso-constriction to cease
      menstrual bleeding remains to be determined.

PMID- 8982750
TI  - Progesterone receptor in Norplant endometrium.
AB  - Endometrial progesterone receptor plays an important role in determining the
      biological activity of progestogens in fertility regulation. Studies during the
      normal menstrual cycle have shown that the concentrations of endometrial
      progesterone receptor and its mRNA vary in glandular epithelia but remain steady
      in stromal cells. There is general agreement between progesterone receptor mRNA
      and protein levels during the normal menstrual cycle. Norplant endometrium had an
      increase in immunoreactive progesterone receptor concentration but a reduction in
      progesterone receptor mRNA levels compared with controls. An immunohistochemical
      study, using the expression of the lysosomal protease cathepsin D as a marker for
      the functional status of progesterone receptors, failed to confirm the
      functionality of the receptors in Norplant endometrium. Together, these results
      suggest that (i) there is a differential sensitivity of glandular and stromal
      progesterone receptors to steroid regulation during the normal menstrual cycle;
      (ii) there appears to be a dissociation between the concentrations of
      progesterone receptor and its mRNA in Norplant endometrium; and (iii) there was
      significantly more progesterone receptor mRNA and lower plasma oestrogen
      concentrations in Norplant subjects with amenorrhoea than with endometrial
      bleeding. The clinical significance of the differences in progesterone receptor
      mRNA levels and plasma oestrogen concentrations between the amenorrhoea group and
      the bleeding group requires further investigation.

PMID- 8982751
TI  - Dual role of angiotensin II in the human endometrium.
AB  - Angiotensin II (ANG) promotes cell proliferation and angiogenesis as well as
      being a potent vasoconstrictor. The cellular distribution of renin, ANG and its
      receptors in the endometrium has yielded useful information about the possible
      role of the renin-angiotensin system in cyclic menstruation. In the early
      proliferative phase, intense ANG-like immunostaining was detected in stroma and
      glandular epithelia, whereas in the late secretory phase, maximal
      immunoreactivity was localized in the perivascular stromal cells around the
      endometrial blood vessels. Quantitative receptor autoradiographic studies
      demonstrated that the human endometrium contains predominantly ANG type 2
      receptor (AT2), with a relatively low expression of ANG type 1 receptor (AT1) and
      a novel non-AT1/non-AT2 ANG recognition site. AT receptors displayed cyclic
      changes, and the highest renin concentration was detected in the late secretory
      phase prior to menstruation. After long-term Norplant treatment, an increase in
      ANG-like immunoreactivity was observed in endometrial stroma and glandular
      epithelia, while in hyperplastic endometrium, ANG-like immunoreactivity decreased
      compared with normal cyclic endometria. The pattern of ANG immunostaining in
      endometria from patients with irregular menstruation was markedly different from
      that detected in normal endometrium. Normal function of the renin-angiotensin
      system in endometrium may be necessary for regular cyclic menstruation, and
      alterations in the distribution of ANG and/or the activity of its receptors are
      likely to be involved in dysfunctional uterine bleeding.

PMID- 8982752
TI  - Oestrogen treatment for increased bleeding in Norplant users: preliminary
      results.
AB  - A clinical study was conducted to assess the effects of oestrogen in controlling
      increased endometrial bleeding problems in the first year of Norplant use. Three
      treatment groups were studied: (i) 50 micrograms ethinyl oestradiol (EE); (ii) a
      combined pill containing 30 micrograms EE and 150 micrograms levonorgestrel
      (LNG); and (iii) placebo. Based on menstrual diary records, women with prolonged,
      frequent or irregular bleeding, as defined by World Health Organization criteria,
      were randomly allocated to one treatment for 21 days. A first endometrial biopsy
      was taken before commencing treatment and a second biopsy at either day 14 or 21
      of treatment. Following treatment, all subjects kept a menstrual diary card for
      90 days. In this preliminary study, 48 subjects had completed the full 90 day
      post-treatment record. Within 21 days of EE treatment, the number of
      bleeding/spotting days was reduced significantly (P < 0.02). In the 90 days
      following treatment, the administration of EE and EE + LNG significantly
      decreased the number of bleeding/spotting days (P < 0.05). There was no reduction
      in the number of bleeding/spotting episodes in the EE and EE + LNG groups, but
      the length of each bleeding/spotting episode was significantly shorter (P <
      0.05). Histopathological findings of endometrium on day 0 revealed consistent
      progestogenic effects, and there was no apparent change in response by day 14 or
      21 of EE or EE + LNG treatment. The results of this study confirm the clinical
      effectiveness of EE and EE + LNG for the treatment of irregular, frequent and
      prolonged bleeding in Norplant users.

PMID- 8982754
TI  - Matrix metalloproteinases in normal menstruation.
AB  - Matrix metalloproteinases (MMP) are strongly implicated in menstruation.
      Messenger RNA for proMMP-1 and -3 was detectable in normal cycle endometrium only
      peri-menstrually and menstrually, although mRNA for their tissue inhibitors, TIMP
      1 and TIMP-2, was present throughout the cycle. MMP-1, -3 and -9 were
      demonstrated immunohistochemically to be specifically associated with degraded
      tissue in menstrual endometrium. Activated mast cells and eosinophils, which
      release regulators of MMP expression and activators of latent enzymes, were also
      a marked feature of menstrual endometrium. Cultured endometrial stromal cells
      released MMP-1, -2, -3 and -9 and TIMP-1 and -2, whereas production by epithelial
      cells was minimal. Progesterone withdrawal from stromal cell cultures (for the
      final 4 days of a 10 day culture) increased the release of all four enzymes: all
      but MMP-2 were also stimulated by interleukin-1 or tumour necrosis factor alpha
      added to short-term stromal cultures. We postulate that an alteration in the
      balance of MMP and their inhibitors and the activation of MMP are prerequisites
      for tissue degradation at menstruation, and that this is regulated by a
      combination of progesterone withdrawal and paracrine factors from epithelial and
      stromal cells and from mast cells and eosinophils.

PMID- 8982753
TI  - The effect of transdermal oestradiol on bleeding pattern, hormonal profiles and
      sex steroid receptor distribution in the endometrium of Norplant users.
AB  - The most common side-effect and reason for discontinuation with Norplant use is
      bleeding disturbance. The aim of this study was to investigate whether the 6 week
      application of a patch which released 100 micrograms/day oestradiol would reduce
      the number of abnormal bleeding days or eliminate the problem. Another objective
      was to find out the correlation between the bleeding pattern and endometrial
      concentrations of oestrogen receptor (ER) and progesterone receptor (PR). Of 98
      Norplant users, 34 patients had normal bleeding patterns and 64 patients had
      abnormal bleeding patterns. An oestradiol patch or a placebo patch were randomly
      used to treat 33 and 31 women with abnormal bleeding respectively. There was a
      clinical improvement in the oestradiol group compared with the placebo group,
      although this was not statistically significant. There were no correlations
      between PR and ER concentration and the serum oestradiol, progesterone,
      levonorgestrel and sex hormone-binding globulin concentrations. Significantly
      increased mean immunostaining scores of stromal PR were observed in those
      Norplant users whose endometrium had an atrophic histological appearance. The
      serum oestradiol concentration did not show a significant change after treatment
      with the oestradiol patch compared with the placebo patch.

PMID- 8982755
TI  - Regulation and restricted expression of interstitial collagenase suggest a
      pivotal role in the initiation of menstruation.
AB  - Collagenases are the only mammalian enzymes able to cleave, at neutral pH, the
      triple helical domain of fibrillar collagens, major constituents of the
      extracellular matrix of the endometrium. Interstitial collagenase is expressed,
      secreted and activated in human endometrium only just before and during
      menstruation. The expression of interstitial collagenase is restricted to the
      areas of the functional layer of the endometrium which are breaking down and to
      fragments which have been shed. In endometrial explants, combined sex steroids
      tightly control the expression, secretion and activation of interstitial
      collagenase, as well as the preservation of the extracellular matrix. These
      observations imply a pivotal role for this proteinase in the initiation of
      menstruation.

PMID- 8982756
TI  - Cytokeratin 8, 18 and 19 in endometrial epithelium of Norplant and norethisterone
      enanthate injectable progestogen contraceptive users.
AB  - Cytokeratins 8, 18 and 19 are members of the cytoskeletal intermediate filament
      family found in all simple epithelia. Intermediate filaments are dynamic
      intracytoplasmic structures that can be influenced by a number of external
      factors. Norethisterone enanthate (NET-EN) is a long-acting progestogen
      contraceptive that has been found to arrest endometrial growth in the rat. Both
      Norplant and NET-EN cause bleeding problems among users which are responsible for
      > 50% of withdrawals with these methods. The aim of this study was to explore
      changes in the expression and distribution of cytokeratins 8, 18 and 19 in NET-EN
      and Norplant-exposed endometrial epithelium which could be related to bleeding
      disturbances. Seven NET-EN and 37 Norplant endometrial biopsies were paraffin
      embedded and stained immunohistochemically to evaluate cytokeratin expression and
      distribution. The results showed that women who had received NET-EN for 3-4
      months had a cytokeratin distribution similar to that seen in the normal
      menstrual cycle. This is in contrast to endometrium from Norplant users in which
      cytokeratin expression was reduced and the epithelial cells were more rounded. No
      relationship between cytokeratin expression and breakthrough bleeding pattern was
      found. NET-EN and Norplant may act differently on endometrial epithelial
      cytokeratin.

PMID- 8982758
TI  - A comparison of mechanisms underlying disturbances of bleeding caused by
      spontaneous dysfunctional uterine bleeding or hormonal contraception.
AB  - Recent research has not been able to demonstrate close endometrial morphological
      correlations with specific abnormalities of menstrual bleeding, but has pointed
      to an increasing number of molecular mechanisms that may be involved in the
      occurrence of certain forms of abnormal uterine bleeding. Ovulatory and
      anovulatory dysfunctional uterine bleeding (DUB) and progestogen-related
      breakthrough bleeding (BTB) are three conditions with quite different clinical
      characteristics. It is also probable that the local endometrial molecular
      mechanisms associated with these three menstrual disturbances are quite
      different. Ovulatory DUB is associated with a series of vascular and haemostatic
      disturbances that all appear to contribute to increased loss of blood and tissue
      fluid at menstruation. Anovulatory DUB is associated with obvious disturbances of
      endometrial histology, vascular morphology and fragility, with variable and
      increased blood flow. Progestogen-related BTB is associated with a multitude of
      morphological and functional endometrial changes that appear to relate
      predominantly to a patchy capillary origin for the bleeding. Many molecular and
      cellular changes have been observed in all three conditions. It is not yet known
      whether there is a single, but different, underlying mechanism responsible for
      these multiple abnormalities in each of the three clinical situations.

PMID- 8982757
TI  - Non-human primate models; artificial menstrual cycles, endometrial matrix
      metalloproteinases and s.c. endometrial grafts.
AB  - Rhesus monkeys are useful models in which to examine the hormonal regulation of
      endometrial matrix metalloproteinases (MMP) and to evaluate the role of MMP in
      uterine bleeding. Artificial 28 day menstrual cycles can be induced in
      ovariectomized monkeys by inserting an oestradiol implant for 2 weeks, then
      inserting a progesterone implant for 2 weeks, and then, with the oestradiol
      implant remaining in place, removing and reinserting the progesterone implant at
      2 week intervals. To examine MMP during menses, we established such cycles and
      removed uteri by hysterectomy at closely spaced intervals before, during and
      after menses, as well as at later time points. Some samples were also obtained
      during menses induced by the withdrawal of both progesterone and oestradiol. We
      examined mRNA of the following MMP by Northern blotting: matrilysin, stromelysin
      1, stromelysin-2, stromelysin-3 and the tissue inhibitor of MMP TIMP-1. The
      expression of these MMP mRNA increased substantially by 2-3 days after
      progesterone withdrawal, whether or not oestradiol was maintained. The expression
      of some of the MMP (stromelysins-1 and -2) returned very rapidly to baseline
      levels by 5 days after progesterone withdrawal, while the expression of others
      (matrilysin, stromelysin-3 and TIMP-1) declined more slowly, reaching a baseline
      level by 10 days after progesterone withdrawal, with little or no further decline
      after progesterone concentrations rose during the induced luteal phase.
      Immunocytochemical studies showed that matrilysin was expressed primarily in the
      glands of the upper functionalis. In other work with the rhesus monkey model, we
      used a s.c. endometrial autograft technique in which pieces of endometrium were
      autotransplanted to the abdominal skin. During menses in the grafts, matrilysin
      was expressed in the glands of the grafts similar to the glands in the eutopic
      endometrium. Endometrial autografts can serve as a useful model for the study of
      MMP in uterine bleeding.

PMID- 8982759
TI  - Future directions for research on endometrial bleeding.
AB  - Disturbances in endometrial bleeding remain a major problem, and the primary
      reason for discontinuation of progestin-only methods of contraception. However,
      some interesting leads were uncovered in the course of this meeting on 'Current
      research on progestin-only contraceptives and endometrial bleeding', and a number
      of suggestions made about techniques and research topics. This paper attempts to
      summarize these suggestions, with a view to stimulating further research. Topics
      identified included the development of objective tests for vessel fragility,
      identification and properties of vessels likely to bleed, the location of
      bleeding vessels, the basis of the increased microvascular density, the integrity
      of the surface epithelium, the state of the stroma, the function of steroid
      receptors, and the properties of progestins and oestrogens. Several animal models
      are discussed, including monkeys, SCID mice and steroid-treated ovariectomized
      mice, and potential therapeutic agents suitable for human use are identified.

PMID- 8982760
TI  - Medicine in relation to society.

PMID- 8982761
TI  - Heart rate variability in the human transplanted heart: nonlinear dynamics and QT
      vs RR-QT alterations during exercise suggest a return of neurocardiac regulation
      in long-term recovery.
AB  - RATIONALE: Functional reinnervation of the transplanted human heart by the
      autonomic nervous system has not been demonstrated. A lack of autonomic control
      of the transplanted allograft is reflected by an increased resting heart rate, a
      sluggish heart rate response to dynamical exercise and a reduced heart rate
      variability. Recent evidence suggests that a measure of deterministic chaos in
      the heartbeat interval series (point correlation dimension, PD2i) is superior to
      the conventional power spectrum or other stochastic measures in detecting changes
      in the mechanism underlying heartbeat generation. METHODS: The PD2i is based on
      the presumption that the variability is determined and patterned, whereas the
      stochastic measures all assume that the variability is around a stationary mean
      and is noise. The PD2i reconstructs the degrees of freedom (number of independent
      variables) in the system that generates the time series examined, and does this
      irrespective of whether the system is stochastic or deterministic and is
      stationary in time. RESULTS: PD2i was determined for heartbeat intervals (RR, ECG
      digitized at 1200 Hz; supine posture) of 23 heart transplant recipients (HTR: 9
      adults, 14 children; 0.04-7.7 years after transplantation) and 21 healthy control
      subjects (CTL; 13 adults, 8 children). The PD2i (+/-SD) averaged 5.4 +/- 0.7 for
      the CTL adults and 5.4 +/- 0.6 for the CTL children. Mean PD2i was reduced after
      transplantation to 1.1 +/- 0.1 in 6 HTRs recorded within 1 year after surgery; in
      one HTR recorded 2 weeks after surgery the mean PD2i was 3.7. Between 1 to 2
      years PD2i was found increased in 2 of 3 subjects and between 2 to 8 years it was
      increased in 13 of 13, but not to control levels. In normal hearts the QT
      subinterval of each heartbeat cycle is associated with inotropy and the RR-QT
      remainder with chronotropy (i.e., the dyastolic interval during which RR is
      primarily regulated). To examine more closely the residual and returning
      heartbeat dynamics of the HTR subjects, these subinterval series were examined
      during mild exercise (40 to 90 Watts) and its recovery. In recent HTRs, resting
      QT and RR-QT were moderately reduced and modulated by exercise and recovery, but
      with an approximate 100 beat latency. In long-term (7-8 years) HTR subjects there
      was a rapid and larger response to exercise/recovery, but compared to normal the
      range was smaller and the complexity of the subinterval trajectories in time was
      simpler. CONCLUSIONS: Recurrence of low-dimensional deterministic dynamics after
      transplantation suggests recovery of neurocardiac control attributable to 1)
      reorganization of the viable intrinsic cardiac nervous system, 2) reinnervation
      by the extrinsic autonomic nervous system, or 3) both.

PMID- 8982762
TI  - Cocaine, Neuroleptics, and tardive dyskinesia as paleocortical escape.
AB  - Human orobuccolingual movement is reviewed in terms of stimulation and inhibition
      within the striatonigral pathways and its domination and control by motor area 4
      and the inhibitory neocortex. Haloperidol, clozapine and cocaine are then
      compared in terms of the effects of each on the physiology and function within
      these areas under normal and certain pathological conditions. Theoretical models
      are then derived that formulate evidence that a unique, previously unreported,
      combination of two distinct neurological circumstances must occur simultaneously
      to satisfy the criteria for pathological orobuccolingual movement.

PMID- 8982763
TI  - Adjunctive brainstem behaviors in the rat.
AB  - Adjunctive behaviors refers to behaviors that are "out of context" and/or
      excessive in amount. The terminology was first used for unexplained behaviors
      associated with food pellet ratio contingencies in food deprived rats (Falk,
      1971). Clinically, unrelated and complex excessive behaviors were also noted with
      brainstem and diencephalic discharges (Andy, 1986, 1989 and 1995; Andy and Jurko,
      1986). The objective of this study was to develop a model of brainstem generated
      adjunctive behaviors in the rat. METHOD: Sixty-one adult rats were used. Kindling
      was induced by mechanical and DC electrical perturbations in the midbrain. Nine
      different treatment groups were established in which lesions and drugs were used
      separately and in different combinations. Cocaine was used to accentuate, and
      dextrorphan to attenuate the kindling process. Behaviors were visually analyzed
      and recorded by video camera; they were not quantified. DC stimulation and EEGs
      were doen with Grass instruments. Recording and stimulation sights were verified
      histologically. RESULTS: A total of 45 different behaviors were elicited. DC
      stimulation kindled subjects had significantly more behaviors than did electrode
      insertion alone and cocaine alone. However, cocaine combined with DC stimulation
      increased the number and intensity of the kindled behaviors. Dextrorphan tended
      to facilitate catatonic and sleep states. Behaviors occurred randomly and were
      unrelated, even when they occurred in clusters. The behaviors were associated
      with four abnormal EEG discharge patterns. CONCLUSION: We speculate that
      brainstem behaviors are innate adjunctive drives that are generated in the
      brainstem reticular formation. They are monitored by the cortex and partially
      modified by environmental and cortical inputs.

PMID- 8982764
TI  - Richard L. Solomon and learned helplessness.
AB  - This article reviews the course of development of research on a currently popular
      explanatory approach to dysfunctional behavior, the learned helplessness
      analysis. The early history is prominent in this review as it reflects the
      inspirations of Richard L. Solomon, a scholar who fostered the resurgence of
      psychologists' interests in Pavlovian conditioning in the 1950s and 1960s.
      Current research is characterized as having four separate themes: elaboration of
      "symptoms," elucidating the role of fear, explicit modeling, and extensions
      involving attributional constructs.

PMID- 8982765
TI  - Pavlov's position toward Konorski and Miller's distinction between Pavlovian and
      motor conditioning paradigms.
AB  - Two Warsaw medical students, Jerzy Konorski and Stefan Miller, having read I.P.
      Pavlov's works on conditional reflexes, informed him in a 1928 letter that they
      had discovered a new type of conditioning. A previously neutral stimulus preceded
      the passive lifting of a dog's paw which then was followed by feeding; this
      stimulus then evoked the spontaneous raising of that paw. Pavlov responded
      informing them that their conditioning of motor responses expanded his theory of
      higher nervous activity, but that their conditioning paradigm-that they named
      CRII-did not differ fundamentally from the Pavlovian conditioning paradigm. The
      replication of the Warsaw experiment in Pavlov's laboratory failed to provide
      unequivocal results. From 1931 to 1933, Konorski, working in Pavlov's Leningrad
      laboratory, further explored the parameters of CRII. Pavlov insisted that the
      conditioning of motor movements differs from the conditioning of other sensory
      analyzers only in that, on the neural level, the motor analyzer is both afferent,
      that is, perceptive, and efferent, that is, responsive. Konorski was not
      convinced, and he subsequently maintained that the two conditioning paradigms
      were fundamentally different.

PMID- 8982766
TI  - The peptide binding specificity of the MHC class II I-A molecule of the Lewis
      rat, RT1.BI.
AB  - The specificity of peptide binding to MHC molecules is defined by binding motifs
      composed of several relatively conserved anchor positions. The peptide binding
      motifs of murine MHC class II I-A molecules are functionally important but poorly
      characterized. Here we use peptide binding studies and isolation of naturally
      presented peptides to characterize the peptide binding motif of the MHC class II
      I-A molecule, RT1.BI, a molecule that is involved in experimental autoimmunity in
      the Lewis rat. We now report that, similar to other class II motifs, the RT1.BI
      motif consists of a nonamer sequence with four major anchor positions (P1, P4, P6
      and P9). Residues at P4 and P9, rather than at P1, appeared to be particularly
      important for binding. Negatively charged residues were favored at P9, consistent
      with the presence of a serine at position 57 of the RT1.BI beta chain. This
      RT1.BI motif could be observed in the dominant autoantigenic T cell epitopes
      mapped previously in the Lewis rat. These results highlight a general similarity
      and some important differences in the organization of MHC class II peptide
      binding motifs. The reported RT1.BI motif should facilitate the prediction and
      design of T cell epitopes for the induction and control of experimental
      autoimmune diseases in Lewis rat models.

PMID- 8982767
TI  - Ly-49 G2+ NK cells are responsible for mediating the rejection of H-2b bone
      marrow allografts in mice.
AB  - NK cells can mediate the specific rejection of bone marrow but not solid tissue
      allografts in lethally irradiated mice. NK cells are also responsible for the
      phenomenon of "hybrid resistance' in which F1 hybrid H-2 heterozygous mice can
      reject parental H-2 homozygous bone marrow grafts. Ly-49C and Ly-49 G2 are
      markers identified on subsets of NK cells. While Ly-49C+ NK cells have been
      demonstrated to mediate the specific rejection of H-2d bone marrow allografts,
      the role of the Ly-49 G2+ NK subset is unclear because depletion of this subset
      in vivo did not affect splenic NK activity against tumor targets. Through bone
      marrow transplantation typing studies, we demonstrate that Ly-49 G2+ NK cells
      complement Ly-49C+ NK cells in that they specifically mediate the rejection of H
      2b bone marrow allografts in lethally irradiated mice. In support of this,
      depletion of the Ly-49C+ NK subset in vivo also enhanced the ability of the mice
      to reject H-2b bone marrow cells suggesting that the depletion was augmenting the
      ability of the Ly-49 G2+ NK cells to reject the marrow allografts. Depletion of
      Ly-49 G2+ NK cells in F1 hybrid mice abrogated their ability to reject parental H
      2b but not H-2d bone marrow grafts. Therefore, Ly-49 G2 denotes a subset of NK
      cells that appears to play a critical role in the recognition of H-2b bone marrow
      cells in allogeneic and F1 hybrid mice.

PMID- 8982768
TI  - Differential regulation of antigen-specific IgG4 and IgE antibodies in response
      to recombinant filarial proteins.
AB  - Having identified two recombinant filarial proteins (Ov27 and OvD5B) that induced
      patient peripheral blood mononuclear cells to produce antigen-specific IgG4/IgE
      antibodies in vitro, we assessed the role these filarial antigens play in
      inducing antigen-specific isotype switching (gamma 4 and epsilon) in the absence
      of T cells. Purified CD19+ s gamma-/s epsilon- B cells were cultured with either
      of these antigens in the presence of anti-CD40 mAb and human IL-4. Both antigen
      and polyclonal signals delivered by IL-4 (or IL-13) were necessary for the
      induction of specific IgG4/IgE antibodies. To assess the role played by cytokines
      produced by B lymphocytes in antigen-driven selection of the gamma 4 or epsilon
      isotype, neutralizing anti-cytokine antibodies were used in vitro. While anti-IL
      12 antibodies did not alter the antigen-specific IgG4/IgE production, anti-IL-6,
      anti-IL-13 and anti-tumor necrosis factor-alpha antibodies significantly
      inhibited the production of IgG4/IgE. Anti-IL-2 and anti-IL-10 antibodies
      appeared to down-regulate antigen-specific IgG4 antibodies without affecting
      antigen-specific IgE antibodies. Although anti-CD21 antibodies had no effect on
      specific IgE antibodies, they up-regulated specific IgG4 antibodies, a finding
      paralleled by anti-CD23 antibodies. These data suggest that certain filarial
      antigen-specific IgG4/IgE responses can be differentially regulated and that
      certain endogenously produced molecules from B cells-such as IL-2, IL-10, CD23
      and CD21-play a significant role in the induction of specific isotypes of antigen
      specific antibodies.

PMID- 8982769
TI  - Cholera toxin B subunit binding to an antigen-presenting cell directly co
      stimulates cytokine production from a T cell clone.
AB  - Cholera toxin (CT) is a powerful immunomodulator with strong adjuvant activity.
      Much of this activity is retained by the binding component alone, cholera toxin B
      subunit (CTB). Little is known about the mechanism of the immunomodulatory
      activity of CTB. In this study, both CT and CTB were found to dramatically
      enhance IL-4 production from a T cell clone stimulated with antigen and the B
      cell hybridoma LB as antigen-presenting cell (APC). Enhancement of cytokine
      production was seen following pretreatment of the APC with CT or CTB, while
      pretreatment of the T cells had no effect. Furthermore, stimulatory activity on
      the APC was stable to fixation with paraformaldehyde, demonstrating that the
      activity was mediated by a surface molecule on the APC. CT-pretreated APC also
      enhanced IL-4 production from anti-CD3 mAb-stimulated T cells, indicating that CT
      was providing a co-stimulatory signal. CT treatment of LB cells did not alter the
      expression of class II MHC molecules, CTLA-4 counter-receptors, LFA-1 or ICAM-1.
      When mAb were raised against the CT-pretreated APC, the only antibodies that were
      found to inhibit IL-4 production were those specific for CTB itself. The
      antibodies blocked even when the CT or CTB were already bound to the APC, arguing
      that co-stimulation was provided by a direct interaction with CTB. Blocking
      experiments suggested that APC-associated CTB molecules are interacting with non
      GM1 receptors on the T cells. This novel finding of CTB-mediated T-B interaction
      provides one of the first potential mechanisms for the adjuvant activity of CTB.

PMID- 8982770
TI  - Functional consequences of the binding of MHC class II-derived peptides to MHC
      class II.
AB  - Three MHC class II-derived synthetic peptides (I-A beta (g7)1-16, I-A beta (g7)52
      77 and I-A alpha (g7)63-82YC) were analyzed for their ability to bind to
      syngeneic and allogeneic MHC class II molecules using a whole cell, competitive
      peptide binding assay. These studies demonstrated that the A beta (g7)1-16
      peptide was able to specifically bind to syngeneic as well as to four allogeneic
      MHC class II molecules. The A alpha (g7)63-82YC peptide bound to self MHC class
      II molecules with a lower relative affinity and was able to bind to three out of
      the four allogeneic cells tested. The binding of the three I-A(g7)-derived
      peptides to the self MHC class II was functionally significant. The A beta (g7)1
      16 and A beta (g7)52-77 peptides inhibited the proliferation of a heat shock
      protein 60 peptide-specific Th1 clone by MHC blockade. Interestingly, the A alpha
      (g7)63-82YC peptide appeared to interact directly with T cells as pretreatment of
      the Th1 clone with this peptide resulted in inhibition of antigen-induced
      proliferation. This phenomenon was analyzed in more detail and it was found that
      this peptide could behave as a partial agonist. Incubation of T cells with the A
      alpha (g7)63-82YC peptide resulted in up-regulation of IL-2R alpha chain
      expression and induction of IFN-gamma secretion. In addition T cells pretreated
      with this peptide were rendered hyporesponsive to further antigenic stimulation.
      Thus, a peptide derived from MHC class II may be used in an immunoregulatory
      capacity.

PMID- 8982772
TI  - Plasmodium falciparum-specific T cell clones from non-exposed and exposed donors
      are highly diverse in TCR beta chain V segment usage.
AB  - Humans lacking previous exposure to Plasmodium falciparum typically have a high
      frequency of malaria-reactive T cells in peripheral blood, which cross-react with
      antigens from other microorganisms. We studied a large number of malaria-specific
      human T cell clones from non-exposed and malaria-exposed donors to determine
      whether this response is oligoclonal, and might therefore be generated by a
      limited number of cross-reactive epitopes. Most clones responded well to schizont
      antigen from three antigenically distinct stocks of P. falciparum. Clones derived
      from the same donor tended to show similar patterns of reactivity to a panel of
      non-malaria antigens from various microorganisms, suggesting that a limited
      number of epitopes were recognized by individuals. However, analysis of the usage
      of V segments of the beta chain of the TCR (TCRBV) revealed no evidence of TCRBV
      restriction in the T cell response, either within individual donors or across all
      donors. An apparent skewing towards TCRBV8 in one donor was shown by two methods
      to be due to in vitro expansion of a single clone: (i) Direct sorting of TCRBV8+
      CD4+ T cells from fresh PBMC did not reveal any enrichment for pRBC-reactive
      cells; (ii) Sequencing of VDJ regions revealed that the TCRBV8 clones were
      identical. Sequences of non-TCRBV8 clones from this donor showed major
      differences in the VDJ junctional region. No differences in TCRBV repertoire
      between non-exposed and exposed donors were observed. These results exclude the
      existence of a malarial superantigen and suggest that the T cell response to
      malaria schizont antigen in non-exposed donors is driven by a large number of
      epitopes.

PMID- 8982771
TI  - B cell antigen receptor signaling links biochemical changes in the class II
      peptide-loading compartment to enhanced processing.
AB  - In B cells, processing of antigens in the context of MHC class II molecules is
      initiated by the binding of antigen to the B cell antigen receptor (BCR). BCR
      mediated processing is highly efficient, as a consequence of the BCR's linked
      roles of delivering antigen to the class II peptide-loading compartment and of
      signaling for increased antigen-processing activity. Evidence is emerging that
      receptor signaling regulates intracellular transport through the activities of
      kinases. These in turn have been implicated in the regulation of small mol. wt
      GTPases which govern membrane transport. Therefore, we investigated the changes
      in the phosphoprotein and GTPase profiles associated with the class II peptide
      loading compartment following BCR cross-linking. We first show that protein
      kinase inhibitors, known to block BCR signal transduction, inhibit BCR-enhanced
      antigen processing, demonstrating the critical dependence of enhanced processing
      on the signaling activity of the BCR. Consistent with this observation, the
      phosphoprotein profile of the class II peptide-loading compartment underwent
      rapid and transient changes following BCR cross-linking. We also observed a
      marked increase in the low mol. wt GTPases associated with the class II peptide
      loading compartment within 5 min of BCR cross-linking. The observed changes in
      both the phosphoprotein and GTPase profiles associated with the peptide-loading
      compartment were blocked by kinase inhibitors and were not accompanied by overall
      gross changes in the protein composition of the subcellular compartments. Thus,
      signal cascades initiated by BCR cross-linking at the plasma membrane are
      translated into changes in specific subsets of regulatory proteins associated
      with the peptide-loading compartment.

PMID- 8982773
TI  - A critical role of IL-2 for the production and gene transcription of IL-5 in
      allergen-specific human T cell clones.
AB  - The role of IL-2 in IL-5 synthesis of human helper T cells was investigated. All
      of the Der f II (a major allergen of house dust mite)-specific T cell clones
      established from atopic asthmatic patients produced both IL-2 and IL-4 upon
      activation (Th0 phenotypes). Recombinant IL-2 induced gene expression and protein
      synthesis of IL-5 in T cell clones that produced IL-5 upon antigenic stimulation.
      Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell
      clones was clearly transcribed in response to IL-2, indicating that the
      approximately 500 bp gene segment 5' upstream of the coding region was
      functionally sufficient for the gene transcription induced by IL-2. IL-2-induced
      IL-5 synthesis as well as proliferation was dependent on tyrosine kinases.
      Moreover, IL-5 production by T cell clones stimulated with immobilized anti-CD3
      antibody was completely abrogated by anti-IL-2 neutralizing antibody, suggesting
      that IL-5 (a Th2 cytokine) synthesis of human helper T cells is dependent on IL-2
      (a Th1 cytokine). Our present findings clearly demonstrated that IL-2, known as a
      T cell growth factor, exerts a cytokine promoting activity on T cells. IL-2
      produced at the site of allergic inflammation might facilitate eosinophilic
      inflammation by inducing IL-5 production in T cells.

PMID- 8982774
TI  - The swine Ig heavy chain locus has a single JH and no identifiable IgD.
AB  - Sequence analysis of 84 V region cDNAs expressed with IgM, IgG and IgA from both
      adult and newborn swine suggested that their JH segments had been derived from
      the same germline JH. Only a single hybridizing JH segment could be identified in
      genomic DNA, in a JH-C mu cosmid and in a Sacl fragment of the cosmid extending 5
      kb 5' of the EnhH. The single germline JH segment mapped 6 kb 5' to C mu. This JH
      had a sequence identical to 40 of 42 JH segments expressed in a newborn piglet
      and 25 of 42 expressed by adult swine. None of the 19 JH segments which varied
      from the germline sequence were identical to each other and half of the
      nucleotide changes were silent. No cosmid DNA hybridizing with heterologous
      probes for C delta could be found within 20 kb 3' of C mu and C delta could not
      be cloned from genomic or cDNA libraries. A conserved IgD fragment could be
      amplified from human, mouse and rat genomic DNA but not from rabbit, swine or
      cattle. We hypothesize that heavy chain organization and constituency in
      homeothermic vertebrates is correlated with the site of secondary antibody
      repertoire development and the mechanism(s) used.

PMID- 8982775
TI  - Inhibitory action of sulfatide, a putative ligand for L-selectin, on B cell
      proliferation and Ig production.
AB  - The interaction of L-selectin and its ligand is widely accepted to mediate
      leukocyte rolling and adhesion on the endothelial surface. Although L-selectin is
      ubiqultously expressed on lymphoid cells, its role in execution of lymphocyte
      functions is unknown. By flow cytometric analysis using mAb specific for
      sulfatide, a putative ligand for L-selectin, we found that sulfatide was
      selectively expressed on B cells, but not on T cells. To elucidate the
      involvement of L-selectin and its ligand in B cell activation, the present study
      was undertaken to investigate effects of sulfatide on T cell-dependent and 
      independent Ig production by B cells. In pokeweed mitogen-stimulated cultures,
      addition of sulfatide resulted in almost complete inhibition of Ig production by
      B cells in the presence of memory CD4+ T cells, whether L-selectin-positive or 
      negative. A similar inhibition of Ig production by sulfatide was found when B
      cells were stimulated with Staphylococcus aureus Cowan I and IL-2. Unlike
      sulfatide, a desulfated form of sulfatide, galactosylaceramide, did not show any
      effects on Ig production by B cells. Maximal inhibition of Ig production was
      observed when sulfatide was added at the early period of culture. Sulfatide
      suppressed effectively proliferation of B cells, but not of T cells. Sulfatide
      competed the binding of anti-L-selectin mAb to B cells, suggesting it could
      interfere B cell activation by blocking L-selectin function. The results suggest
      a novel role of the L-selectin/its ligand system in the initiation of B cell
      activation.

PMID- 8982776
TI  - Biological activity of IL-4 and IL-13 on human endothelial cells: functional
      evidence that both cytokines act through the same receptor.
AB  - The cytokine IL-4 has unique effects on human endothelial cells. It specifically
      increases expression of vascular cell adhesion molecule (VCAM)-1 promoting
      adhesion of lymphocytes but not neutrophils, and causes profound effects on the
      morphology of endothelial monolayers characterized by formation of cell clusters
      and the appearance of holes in the cultured monolayer. In this study we show that
      the effects of IL-13 on human umbilical vein endothelial cells (HUVEC) are
      indistinguishable from those of IL-4. Both cytokines induce the same
      morphological changes in cultured HUVEC monolayers which are distinct from any
      other cytokine. In addition, IL-13 and IL-4 stimulate comparable levels of VCAM-1
      expression with similar time kinetics, but at doses 10-fold less than those
      required for B cell activation and proliferation. Using a combination of mutant
      IL-4 antagonists and mAb to the IL-4R alpha chain (CD124), we show that
      expression of IL-4R alpha is essential for HUVEC responses to both IL-4 and IL
      13, consistent with this receptor subunit being a component of the receptors for
      both cytokines. In contrast, the common gamma chain (gamma c), which is a
      component of the classical IL-4 receptor, was not detected on endothelial cells
      by flow cytometry or immunogold histochemistry. In addition, RT-PCR showed
      extremely low or absent gamma c mRNA, consistent with the absence of detectable
      surface protein. These results strongly suggest that the cytokines IL-4 and IL-13
      are both important in modulating endothelial cell function, and may act through a
      single receptor complex on human endothelial cells that includes the IL-4R alpha
      chain but not the gamma c chain.

PMID- 8982777
TI  - CD28-B7 interactions function to co-stimulate clonal deletion of double-positive
      thymocytes.
AB  - Negative selection of thymocytes only occurs if next to signals through the TCR,
      additional antigen-presenting cell (APC)-derived signals are also provided. It
      has been unclear which molecular interactions lead to the generation of these
      signals. In particular, the involvement of CD28 and its ligands B7-1 and B7-2 has
      been controversial. In the present study, we re-address this issue and first
      confirm that cross-linking CD28 molecules on thymocytes can indeed complement TCR
      derived signals for induction of deletion upon TCR engagement with antibodies.
      Furthermore, we extend these findings by documenting that also peptide agonist
      induced deletion can be co-stimulated by antibody-mediated engagement of CD28.
      Additionally, blocking B7-1 or B7-2 reduces negative selection induced by both
      anti-CD3 and peptide agonist in suspension cultures and in fetal thymic organ
      culture. At the same time, prominent co-stimulation of TCR-induced deletion could
      be provided by a B7-negative cell line. Together these results definitively
      demonstrate that CD28-B7 interactions can function to co-stimulate induction of
      clonal deletion, while yet to be identified B7-independent co-stimulatory signals
      can fulfil this function as well.

PMID- 8982778
TI  - Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic
      human subjects.
AB  - We tested peptide immunotherapy in cat-allergic humans, using a formation of two
      synthetic peptides, IPC-1 and IPC-2, each of which is 27 amino acids long and
      contains T cell-reactive regions of Fel d 1, the major cat allergen. In this
      exploratory, randomized, double-blind, parallel-group study, 42 subjects received
      s.c. injections of treatment peptides 250 micrograms or placebo weekly for four
      consecutive weeks. Changes in immediate- and late-phase skin test reactivity, and
      in antigen-driven cytokine synthesis were assessed. Epicutaneous (end-point
      titration) and intradermal tests were performed with cat extract (ALK SQ Cat
      Hair) containing Fel d 1, before the first injection, then 2, 6 and 24 weeks
      after the fourth and last injection of peptides or placebo. IL-4, IL-10 and IFN
      gamma expression by circulating peripheral blood mononuclear cells (PBMC) in
      response to cat extract was measured using short-term bulk culture of PBMC and
      short-term limiting dilution analysis. Subjects who received peptide
      immunotherapy did not tolerate significantly more cat extract containing Fel d 1
      in the skin tests 2, 6 or 24 weeks after the last injection than they did at
      baseline, and their late-phase responses did not decrease significantly compared
      to baseline. Substantial IL-4, IL-10 and IFN-gamma responses were observed
      following primary culture of cat antigen-stimulated PBMC; however, the intensity
      of cytokine synthesis and the IFN-gamma: IL-4 ratio were unchanged in peptide-
      and placebo-treated groups 6 and 24 weeks after the last injection. A few hours
      after the injections, subjects receiving peptides reported more allergic rhinitis
      and asthma symptoms and more pruritus than those receiving placebo. We conclude
      that under the conditions tested, peptide immunotherapy did not reduce immediate-
      or late-phase skin reactivity to cat extract containing Fel d 1 or modify cat
      antigen-specific cytokine production significantly.

PMID- 8982779
TI  - Physical and functional association of CD45 and CD3-TCR complex on CD1+ human
      thymocytes. Evidence that the engagement of CD45 molecules can prevent CD1+
      thymocytes from apoptosis.
AB  - In this study the effects of CD45 engagement on CD3-TCR-driven stimulation of
      CD1+ human immature thymocytes have been analyzed. Simultaneous cross-linking of
      CD45 and CD3 antigens on highly purified CD1+ thymocytes reduced the number of
      cells undergoing apoptosis after 16 h of in vitro culture. This cell population
      might represent immature thymocytes committed in vivo to die by programmed cell
      death (PCD). CD45 engagement could also increase the number of cycling CD1+
      thymocytes; of note, the large majority (> 95%) of dividing cells expressed the
      CD1 molecule at the cell surface, indicating that proliferating cells were
      actually represented by immature thymocytes. These data suggest that the CD45
      molecule might play a role in the rescue of immature thymocytes from PCD during
      differentiation. Along this line, we found that activation of CD1+ thymocytes via
      the CD3-TCR complex could be enhanced by CD45, both in terms of transcription and
      surface expression of IL-2R. These effects might be explained by the finding that
      the CD45 molecule (but not its isoforms CD45RO and RA) was physically associated
      with the CD3-TCR complex at the cell surface of CD1+ human thymocytes, as shown
      by co-precipitation and co-capping experiments. Finally, cross-linking of CD45
      and CD3 antigens led to the expansion of CD3+ thymocytes co-expressing CD4 and
      CD8, indicating that simultaneous engagement of CD45 and CD3 molecules can block
      CD1+ cells at the double-positive (CD3+CD4+CD8+) differentiation stage. On the
      other hand, stimulation through CD3 resulted in the expansion of thymocytes
      showing a mature phenotype (CD3+CD4+ or CD3+CD8+). Altogether, these findings
      suggest that the CD45 molecule is involved both in early activation and in the
      regulation of CD1+ thymocyte differentiation.

PMID- 8982780
TI  - Direct binding of IL-12 to human and murine B lymphocytes.
AB  - IL-12 has been shown to play a central role in cell-mediated inflammatory
      reactions through direct activation of T cells and NK cells. IL-12 also strongly
      influences humoral immunity but these effects have been thought to be indirect
      and caused by intermediary cytokines. Using flow cytometry, we now show that IL
      12 directly interacts with B cells. Freshly isolated murine peritoneal B-1 and
      conventional B lymphocytes bound IL-12, but splenic B cells failed to react
      unless first stimulated with lipopolysaccharide. All murine B cell sources were
      found to express IL-12R beta 1 subunit transcripts as detected by PCR and RNase
      protection assays. IL-12 binding was also detected on phytohemagglutinin
      stimulated human T cell blasts and Staphylococcus aureusl IL-2-stimulated B cell
      blasts but not on freshly isolated peripheral blood lymphocytes. Similarly, IL-12
      directly bound to the human SKW6.4 Burkitt's B cell lymphoma line. In all cases
      positive staining was ablated by omitting IL-12 from the procedure, showing that
      it was not due to detection of endogenous IL-12. These findings indicate that B
      cells represent another major target for IL-12 in addition to T and NK cells, and
      that IL-12 can directly affect humoral immunity.

PMID- 8982781
TI  - Human Th2-like cell clones induce IL-12 production by dendritic cells and may
      express several cytokine profiles.
AB  - Previous studies have shown that human Th2 cells, unlike their murine
      counterparts, retain the ability to produce IFN-gamma upon activation in the
      presence of exogenous IL-12. Here we first extended this notion by showing that
      Th2-like cell clones (Th2C) are also capable of inducing IL-12 production by
      physiological antigen-presenting cells (APC); we next showed that these cells may
      express several distinct cytokine profiles depending upon the activation signal
      and the type of APC with which they interact. We have analyzed the production of
      IL-4, IL-5 and IFN-gamma by Th2C stimulated by either anti-CD3 mAb or exogenous
      IL-2, using peripheral blood monocytes or dendritic cells (DC) as accessory
      cells. We found that: (I) DC but not monocytes released IL-12 and promoted IL-12
      dependent IFN-gamma production upon interaction with anti-CD3- or IL-2-stimulated
      Th2C and (II) ligation of CD3 was required for the production of IL-4 but not of
      IL-5 or IFN-gamma. Thus, depending upon the type of APC with which they
      interacted and the mode of activation, Th2C, expressed four distinct cytokine
      profiles: (i) IL-4 + IL-5, in response to anti-CD3 + monocytes; (ii) IL-4, IL-5 +
      IFN-gamma, in response to anti-CD3 + DC; (iii) IL-5 + IFN-gamma, in response IL-2
      + DC; and (iv) IL-5 alone, in response to IL-2 + monocytes. The ability of human
      Th2-like cells to induce IL-12 production and to release the proinflammatory
      cytokines IFN-gamma and IL-5 upon IL-2-driven interactions with APC may
      contribute to explain how local infection exacerbates Th2-mediated diseases, like
      bronchial asthma and atopic dermatitis.

PMID- 8982782
TI  - Decreased production of IL-2 and IFN-gamma by stimulated splenocytes from mice
      bearing plasma cell tumors is associated with alteration of DNA-binding factors.
AB  - We have previously demonstrated that polyclonally stimulated splenocytes as well
      as enriched T cells from mice bearing plasma cell tumors (PCT) show decreased
      production of the Th1-associated cytokines, IL-2 and IFN-gamma. This observed
      loss of IL-2 and IFN-gamma production could be attributed to possible alterations
      in various factors required for T cell activation and cytokine production. We
      find that B7 co-stimulatory molecules and IL-2R are up-regulated normally on
      splenocytes from PCT mice. Concanavalin A (Con A) stimulation of splenocytes from
      PCT mice in the presence of immobilized anti-CD28 antibody does not enhance
      proliferation. Exogenous rIL-2 addition to cultures of splenocytes from PCT mice
      also does not enhance proliferative responses or cytokine production.
      Furthermore, we do not observe inhibition of normal splenocyte proliferation and
      IL-2 production in the presence of splenocytes from PCT mice, suggesting that the
      appearance of suppressor cells cannot account for the decreased responses by
      splenocytes from PCT mice. Also, IL-2 mRNA levels are decreased in stimulated
      splenocytes from PCT mice, suggesting that there may be an alteration of
      transcription factors required for activation of IL-2. Therefore, we have
      evaluated the DNA-binding activity of transcription factors involved in
      activation of IL-2 and IFN-gamma gene transcription. We find that binding
      activities of AP-1, Oct-1 and Oct-2 transcription factors in stimulated
      splenocytes from PCT mice are similar to normal splenocytes. However, the binding
      activities of NF-kappa B complexes and factors that bind to the proximal
      conserved element in the IFN-gamma promoter are dramatically altered in
      splenocytes from PCT mice. These results suggest that PCT induce changes in
      certain transcription factors that are important for anti-tumor responses,
      including T cell proliferative responses and Th1-associated cytokine production.

PMID- 8982783
TI  - Sex differences in parasite infections: patterns and processes.
AB  - Sex differences in parasite infection rates, intensities, or population patterns
      are common in a wide range of taxa. These differences are usually attributed to 1
      of 2 causes: (1) ecological (sociological in humans); and (2) physiological,
      usually hormonal in origin. Examples of the first cause include differential
      exposure to pathogens because of sex-specific behavior or morphology. The second
      cause may stem from the well-documented association between testosterone and the
      immune system; sexually mature male vertebrates are often more susceptible to
      infection and carry higher parasite burdens in the field. Although many
      researchers favor one explanation over the other, the requisite controlled
      experiments to rule out confounding variables are often neglected. We suggest
      that sex differences in disease have evolved just as sex differences in
      morphology and behavior, and are the result of selection acting differently on
      males and females. Research has often focused on proximate mechanistic
      explanations for the sex difference in infection rates, but it is equally
      important to understand the generality of the patterns in an evolutionary
      context. Because males potentially gain more than females by taking risks and
      engaging in competition, sexual selection pressure has shaped male behavior and
      appearance to maximize competitive ability and attractiveness. Many of the
      classic male attributes such as antlers on deer are testosterone-dependent,
      putting males in what appears to be a cruel bind: become vulnerable to disease by
      developing an attractive secondary sexual ornament, or risk lowered mating
      success by reducing it. A variety of hypotheses have been put forward to explain
      why males have not circumvented this dilemma. The mating system of the host
      species will influence the likelihood of sex differences in parasite infection,
      because males in monogamous species are subject to weaker sexual selection than
      males in polygynous species. Whether these evolutionary generalizations apply to
      invertebrates, which lack testosterone, remains to be seen.

PMID- 8982784
TI  - Nematode spliced leaders--ubiquity, evolution and utility.
AB  - Most nematode messenger RNAs (mRNAs) have at their 5' end a common 22 nucleotide
      leader sequence, the trans-spliced leader or SL1. The presence of this leader on
      some but not all mRNAs raises several questions: What is the role of the spliced
      leader in mRNA maturation, stability and translation? Why do some genes have a
      spliced leader and others not? What is the evolutionary origin of this trans
      splicing mechanism? Recently, additional trans-spliced leaders (SL2, 3, 4, 5)
      have been described. What role do these variants play in nematode gene
      expression? While definitive answers to these questions remain elusive, it is
      clear that the spliced leader will significantly facilitate the cloning and
      sequence analysis of most nematode mRNAs.

PMID- 8982785
TI  - The possibility of an "X" factor. The first documented drug resistance of human
      malaria.
AB  - Malaria was the major cause of casualties among allied forces in the South West
      Pacific campaigns during 1942 and 1943, despite the suppressive use of quinine
      and later atebrin. Clinical experiments undertaken at the Land Headquarters
      Medical Research Unit of the Australian Army in Cairns, under the direction of
      Neil Hamilton Fairley, demonstrated that atebrin was able to provide complete
      protection against vivax and falciparum malaria. Fairley presented the
      experimental results to army commanders in a specially convened conference at
      Atherton, Queensland, in June 1944 and persuaded the army that the solution to
      the malaria problem was for men to take 1 tablet (100 mg) of atebrin each day
      with unvarying regularity while in a malarious area and for 4 weeks afterwards.
      Subsequently, rigid atebrin discipline was adopted and the incidence of the
      disease amongst Australian soldiers in New Guinea during 1945 fell to the lowest
      levels ever recorded to that time by non-immune troops operating for extended
      periods in highly endemic malarious areas. The one exception to this
      unprecedented achievement was during the Aitape-Wewak campaign when an epidemic
      of falciparum malaria developed despite the use of suppressive atebrin. An
      investigation of this epidemic, involving chemotherapeutic experiments of malaria
      derived from specially selected patients evacuated to Cairns, showed that some of
      the parasites were resistant to atebrin. This paper provides an account of how
      the epidemic was dealt with by commanders in the field; how suspected atebrin
      resistant cases came to light; and how these cases were dealt with
      experimentally. The emergence and spread of drug-resistant falciparum malaria has
      since become a key factor limiting man's endeavour to combat the disease. The
      investigation of the Aitape-Wewak epidemic involved the first systematic field
      and laboratory studies on the resistance of human malaria to any drug. From the
      scientific point-of-view, it broke new ground and covered uncharted territory
      which had not been explored previously by other workers. These observations
      formed the solid foundations on which later advances in this field subsequently
      have developed.

PMID- 8982786
TI  - Infection of sheep with adult and larval Ostertagia circumcincta: effects on
      abomasal pH and serum gastrin and pepsinogen.
AB  - Infection of sheep with adult or larval O. circumcincta increased serum
      pepsinogen and gastrin and abomasal pH. The upper limits of the normal range,
      calculated from over 1000 samples collected from parasite-naive sheep, were set
      at 2 standard deviations above the mean; these were for serum pepsinogen, 454 mU
      tyrosine l-1; serum gastrin, 64 pM and abomasal pH, 3.26. Five infection regimes
      were used: sheep previously exposed to field parasitism were infected with 30,000
      larvae intraruminally (Group A), while parasite-naive sheep were administered
      either 50,000 larvae intraruminally (Group B), 150,000 larvae intraruminally
      followed by a trickle infection of 10,000 larvae thrice weekly from days 21 to 45
      (Group C), 150,000 exsheathed larvae via an abomasal cannula (Group D) or 15,000
      adult worms via an abomasal cannula (Group E). Whereas the presence of adult
      worms rapidly increased serum pepsinogen (after 8 h) and abomasal pH and serum
      gastrin (after about 19 h), the early infective larval stages, regardless of the
      infection regime, had minimal effects until the abrupt rise in all parameters 5-6
      days after infection. Abomasal pH returned to near normal levels when the
      infections became patent and was not re-elevated by a subsequent trickle
      infection, whereas serum gastrin and pepsinogen remained high. The initial
      hypergastrinaemia was coincident with the increased abomasal pH, but was preceded
      by the increase in serum pepsinogen. In several sheep, serum pepsinogen increased
      very little during the parasitism, although there were typical effects on
      abomasal pH and serum gastrin. Serum gastrin was depressed when the abomasal pH
      exceeded about 5.5. It is suggested that an inhibitor of gastrin release is
      generated by proliferating abomasal microbes under these conditions and that this
      is a limitation to the use of elevated serum gastrin in the diagnosis of
      parasitism in individual sheep.

PMID- 8982788
TI  - In vitro studies on intraspecific and interspecific chemical attraction in
      daughter rediae of Echinostoma trivolvis and E. caproni.
AB  - In vitro pairing and aggregation studies on daughter rediae of Echinostoma
      trivolvis and E. caproni were done at 22 degrees C in a Petri dish bioassay
      containing an agar substratum and a Locke's solution overlay. Pairing or
      aggregation was considered positive when rediae were in contact or within 1 mm of
      each other. Intraspecific and interspecific pairing or aggregation occurred in
      the bioassay when rediae were initially placed 5 or 10 mm apart. Movement of a
      single redia in the bioassay to a dialysis sac containing 1-10 rediae showed that
      intraspecific and interspecific pairing occurred in the absence of redial tactile
      stimulation. Movements of single rediae in the bioassay to agar plugs impregnated
      with redial excretory/secretory (ES) products occurred. The lipophilic fraction
      of the ES products was significantly more attractive than the hydrophilic
      fraction. The significance of redial chemical communication is not clear.

PMID- 8982787
TI  - Do excretory-secretory products of Onchocerca gibsoni contain phosphorylcholine
      attached to O-type glycans?
AB  - Excretory-secretory products (ES) of adult male Onchocerca gibsoni contain
      phosphorylcholine (PC). PC-ES are detected as a smear of M(r) approximately 60-
      approximately 200 kDa by western blotting employing a monoclonal antibody (mAb)
      against PC, suggesting that they are glycoproteins. Exposure of PC-ES to N
      glycosidase F results in weak and inconsistent loss of binding of the mAb,
      indicating that unlike the situation with respect to ES of Acanthocheilonema
      viteae, PC is highly unlikely to be solely attached to N-type glycans.
      Conversely, treatment of O. gibsoni PC-ES with mild alkali, a strategy for
      removing O-type glycans, abolishes mAb binding. These results suggest that PC may
      be attached to O. gibsoni proteins mainly via O-type glycans, and raise the
      possibility that filarial parasites may vary with respect to their mode of
      attachment of PC. The implications of this with respect to the design of
      inhibitors of PC attachment for use as anti-filarial drugs, are discussed.

PMID- 8982789
TI  - Persistence of ivermectin in plasma and faeces following treatment of cows with
      ivermectin sustained-release, pour-on or injectable formulations.
AB  - Sixteen young dairy cows were randomly allocated to 4 groups of 4 animals each:
      Group 1 cows were each given a single Ivomec SR Bolus; Group 2 cows were treated
      with the Ivomec Pour-on formulation; Group 3 cows were injected with the Ivomec
      Subcutaneous Injection; Group 4 cows were untreated controls. Blood and faecal
      samples were collected from all cows on the day before treatment and on days 1,
      2, 3, 7, 14, 21, 28, 35, 42 and 49 after treatment for HPLC determination of
      plasma and faecal ivermectin concentrations. Group 1 (SR Bolus) cows had mean (+/
      S.D.) plasma ivermectin concentrations ranging from 5.6 +/- 1.8 micrograms l-1
      (p.p.b.) at 14 days to 11.0 +/- 4.7 micrograms l-1 at 49 days. Faecal ivermectin
      concentrations were little changed from 4.0 +/- 2.0 micrograms g-1 (p.p.m.) dry
      wt (dry weight) [0.5 +/- 0.2 microgram g-1 wet wt (wet weight)] at 14 days to 3.0
      +/- 2.0 micrograms g-1 dry wt (0.5 +/- 0.4 microgram g-1 wet wt) at 49 days.
      Group 2 (Pour-on) cows showed a rapid rise in plasma concentrations to 32.9 +/-
      15.7 micrograms l-1 2 days after treatment, followed by a gradual decline to 1.3
      +/- 0.07 micrograms l-1 at 28 days. Faecal ivermectin concentrations rose sharply
      to 18.5 +/- 7.4 micrograms g-1 dry wt (2.8 +/- 1.2 micrograms g-1 wet wt) 2 days
      after treatment, then fell to 0.04 +/- 0.004 microgram g-1 dry wt (0.006 +/-
      0.0004 microgram g-1 wet wt) at 28 days. Group 3 (Injection) cows also showed a
      rapid rise to an early plasma peak of 46.1 +/- 22.7 micrograms l-1 3 days after
      treatment, followed by a gradual decline to 1.3 micrograms l-1 at 35 days. Faecal
      ivermectin concentrations rose to 1.2 +/- 0.34 micrograms g-1 dry wt (0.2 +/-
      0.05 microgram g-1 wet wt) at 3 days, declining to 0.08 +/- 0.0001 microgram g-1
      dry wt (0.01 +/- 0.0008 microgram g-1 wet wt) at 28 days. No ivermectin was
      detected in the plasma or faeces of Group 4 (Control) cows. Concentrations of
      ivermectin potentially toxic to dung-breeding or dung-feeding invertebrates were
      excreted for the duration of the study in dung of cows treated with the SR Bolus
      and for 28 days in the dung of cows treated with the Pour-on or injectable
      formulations.

PMID- 8982790
TI  - The gametocytes of Plasmodium vinckei petteri, their morphological stages,
      periodicity and infectivity.
AB  - Gametocyte production by P. vinckei petteri was cyclic, occurring at each
      schizogony every 24 h. They matured in 27 h from merozoite to type 0
      microgametocyte, in 3 h from type 0 to type I, 6 h from type I to type II and 3 h
      from type II to type III. Transmission experiments showed that the time of
      maximum infectivity was midday when mice were inoculated at midnight, and
      midnight when mice were inoculated at midday. In all instances, maximum
      infectivity coincided with a peak in intensity by type II microgametocytes, a
      relationship confirmed by multiple correspondence analysis. The proportion of
      type II microgametocytes was higher in the mosquitoes blood meal than in smears
      of tail blood of mice, suggesting a sequestration phenomenon with this stage.

PMID- 8982791
TI  - Anaplasma marginale: detection of carrier cattle by PCR-ELISA.
AB  - A highly sensitive and specific polymerase chain reaction (PCR) based assay for
      the detection of the minute levels of Anaplasma marginale present in the blood of
      long-term carrier cattle was developed. A simple lysis method was used to remove
      most of the haemoglobin from the blood to facilitate direct input of samples into
      the PCR reactions without prior purification of the DNA. PCR product was detected
      by enzyme-linked immunosorbent assay (ELISA) to simplify the processing of large
      numbers of samples. The sensitivity limit of the PCR-ELISA was 0.00015%
      parasitaemia (24 infected erythrocytes per microlitre of blood). No cross
      reactivity of the assay was observed when A. marginale-negative blood infected
      with Babesia bovis or Theileria orientalis was tested. The PCR-ELISA was shown to
      be 92% efficient in the detection of long-term A. marginale carrier cattle. No
      false-positive results were obtained. These results compared favourably with 2
      serological assays for detection of A. marginale carrier cattle (card
      agglutination test and ELISA) which were applied to the same experimental
      animals.

PMID- 8982792
TI  - Freeze-fracture cytochemistry of membrane cholesterol in Blastocystis hominis.
AB  - Membrane cholesterol in Blastocystis hominis was detected by freeze-fracture
      methods using a polyene antibiotic, filipin. Since the intramembrane particles
      (IMP) were distributed heterogeneously on both plasma and vacuole membranes, many
      IMP-free areas were observed. Even in filipin-treated cells, filipin-cholesterol
      complexes were not detected in IMP-free areas on the plasma membrane, whereas on
      the central vacuole membrane the complexes were mainly observed in IMP-free
      regions. These results indicate the different organization of the membrane
      cholesterol between the plasma membrane and central vacuole membrane. Most of the
      granules in the central vacuole were densely labeled with filipin, indicating the
      accumulation of cholesterol in the vacuole.

PMID- 8982793
TI  - Antifilarial and trypanocidal properties of phenothiazines and related
      polycyclics as new lead structures.
AB  - New phenothiazine derivatives and 4 related lead structures have been studied for
      their antifilarial and trypanocidal properties. Regarding phenothiazine
      derivatives, the nitrile group at the 3 position on the phenothiazine ring had a
      strong in vitro antifilarial effect against Molinema dessetae infective larvae.
      Among the 4 new lead structures, compound 4 or naphtho(2',3': 4,5) thiazolo(3,2
      a)benzimidazole-7,12-dione was the most antifilarial, with IC50 of 8 microM at
      day 8. These results justify further studies in vivo. A slight effect was
      observed against the trypanosomes maintained in vitro since minimum inhibitory
      concentrations of active compounds were 50 microM after a 24-h incubation period.
      Nevertheless, no trypanocidal activity was observed in vivo after a 100 mg kg-1
      treatment and the compound 3 or dibenzo(b,f)(1,4)thiazine-11-amine was lethal at
      this dose. These new lead structures have now to be optimised using pharmaco
      modulations.

PMID- 8982794
TI  - Immunomodulation of sheep and human lymphocytes by Fasciola hepatica excretory
      secretory products.
AB  - Fasciola hepatica excretory-secretory (ES) products (30 micrograms ml-1 total ES
      protein upwards) significantly decreased tritiated thymidine (3HTh) uptake in
      phytolectin-stimulated sheep lymphocytes. Lower doses of ES products, however,
      caused an increase in 3HTh uptake in sheep cells stimulated with
      phytohaemagglutinin (PHA) and Concanavalin A (Con A) and, indeed, ES products
      were mitogenic on their own. In contrast, 3HTh uptake by human lymphocyte
      cultures in the presence of phytolectins was progressively inhibited by
      increasing doses of ES products, and ES products were not mitogenic on their own.
      The observed inhibitory effects on 3HTh incorporation were not due to toxicity of
      ES products.

PMID- 8982795
TI  - The ITS-2 rDNA of Teladorsagia circumcincta, T. trifurcata and T. davtiani
      (Nematoda: Trichostrongylidae) indicates that these taxa are one species.
AB  - There remains uncertainty about the species status of Teladorsagia circumcincta,
      T. davtiani and T. trifurcata. In this study, the second internal transcribed
      spacer (ITS-2) sequences of these taxa and 2 other members within the same
      subfamily (Ostertagiinae) were examined. Although some sequence variation was
      detected between and within single worms of each taxon of Teladorsagia, no
      unequivocal base differences were detected among their consensus ITS-2 sequence.
      In comparison, there was 9% sequence difference between O. ostertagi and O.
      leptospicularis and 13-15% difference between the genera Teladorsagia and
      Ostertagia. These findings indicate that T. circumcincta, T. davtiani and T.
      trifurcata represent a single species, T. circumcincta.

PMID- 8982796
TI  - How many parasite species are there: are we close to answers?

PMID- 8982797
TI  - Are the 26-kDa somatic and the 24-kDa excretory/secretory antigens of Haemonchus
      contortus one and the same?

PMID- 8982798
TI  - Quality of life of the spouses of stroke patients: a preliminary study.
AB  - To study the global quality of life (QOL) of spouses of chronic stroke patients,
      and to determine its most pertinent factors, we assessed nine stroke patients and
      their spouses, using the Barthel index, the Functional Independence Measure
      (FIM), the Montgomery and Asberg Depression Rating Scale (MADRS), the
      Reintegration to Normal Living Index (RNLI), and a 10-cm visual analogue scale
      (VAS) to evaluate spouses' QOL. Correlation analysis was performed with the
      Spearman rank correlation analysis. Mean age of spouses was 53.6 +/- 11.3 years
      (male:female ratio, 8:1). The mean interval from stroke was 17.6 +/- 10.6 months.
      The spouses' median QOL score was 4.9, with a significant correlation between
      spouses' QOL scores and patients Barthel index scores, FIM global scores, and FIM
      locomotion scores. Spouses complained of the physical burden, but psychological,
      social, economic and marital consequences of the stroke were also reported. This
      study confirms the constant impact of stroke on the QOL of the spouses, and
      demonstrates the role of patients' physical disability. However, the VAS allows
      only a global approach. A self-administered composite index, exploring the
      consequences of the stroke on the spouses' daily life, would be a useful
      complement.

PMID- 8982799
TI  - Effective teamwork in rehabilitation.

PMID- 8982800
TI  - Parental perceptions of a short conductive education programme.

PMID- 8982801
TI  - Levels of engagement in hospital and community-based homes for people with
      learning disabilities: can individual characteristics account for differences?

PMID- 8982802
TI  - Life satisfaction in persons with lacunar infarction--a comparative analysis of
      two measures of life satisfaction.

PMID- 8982803
TI  - Inpatient rehabilitation: the correlation between functional gains and
      appropriateness of admissions.
AB  - All admissions to an acute rehabilitation unit were later critiqued by the
      rehabilitation team to determine appropriateness of admissions. The physiatrist
      alone evaluated the patient for admission. From the team which worked with the
      patient, a physical therapist, occupational therapist and a nurse were asked to
      evaluate the appropriateness of the admission; a decision on appropriateness had
      to be supported by at least two of these three. The team scored patients with the
      Functional Independence Measure (FIM) on admission, weekly, and at discharge. In
      a six-month period there were 60 appropriate admissions and ten inappropriate
      admissions. The average length of stay was 38.3 days for appropriate and 17.3
      days for inappropriate admissions. The appropriate gorup had an average initial
      FIM score of 40.6 and discharge score of 66.6. The inappropriate group started
      with high FIM scores, with an average of 61.0, and did not significantly improve
      their scores. Their average discharge score was 70.0. The rate of progress
      (efficiency ratio), in points per day, was 0.81 for the appropriate and 0.36 for
      the inappropriate group. Thus, there is a strong positive correlation between the
      rate of progress and appropriateness as assessed at discharge by the
      multidisciplinary team [corrected].

PMID- 8982804
TI  - A study on the utility of functional assessment for teachers of children with
      mental retardation.

PMID- 8982805
TI  - The Rehabilitation Success Rate: an organizational performance indicator.

PMID- 8982806
TI  - Hand-held dynamometer measurements obtained in a home environment are reliable
      but not correlated strongly with function.

PMID- 8982807
TI  - Ultrastructure and distribution of axon terminals from the reticular thalamic
      nucleus to the anteroventral thalamic nucleus of the rat.
AB  - Ultrastructure of axon terminals projecting to the anterovetral thalamic nucleus
      (AV) from the reticular thalamic nucleus (RTN) of the rat was studied by using
      the anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA
      HRP). Anterogradely labeled fibers were distributed in ventral and caudal parts
      in AV following WGA-HRP injections into the medial part of rostral RTN, whereas
      labelings were found in the anterodorsal thalamic nucleus (AD) and dorsal part of
      AV following injections into the dorsal part of rostral RTN. The main labeled
      terminals were small to medium in size, containing pleomorphic vesicles, and made
      symmetrical contacts on wide range of neuronal surfaces, including cell bodies,
      dendritic shafts and their spines. Majority of these terminals made a single
      synaptic contact, whereas some labeled terminals had two synaptic contacts on two
      different postsynaptic profiles, such as on both soma and large dendrite, on both
      soma and small dendrite, on both soma and dendritic spine, and on both large and
      small dendrites.

PMID- 8982808
TI  - Cholecystokinin-like immunoreactivity in cat inferior colliculus. Light and
      ultrastructural study.
AB  - Cholecystokinin-like immunoreactive (CCK-LI) neurons are observed in the
      pericentral nucleus, the external nucleus and the dorsomedial part of the central
      nucleus of the cat's inferior colliculus. The largest number of CCK-LI cell
      bodies is observed in the caudal part of the pericentral nucleus. Using the
      electronmicroscopical examination we distinguish two different types of CCK-LI
      neurons. The first type CCK-LI neurons is characterized by a relatively large
      nucleus, surrounded by a dark rim of cytoplasm containing single cisterns of
      granular endoplasmic reticulum, few mitochondria and lysosomes. The second type
      CCK-LI neurons are smaller than the neurons of the first type. The nucleus is
      relatively larger while the cytoplasmic rim is quite thin. The CCK-LI
      immunoreactivity is also found in the large, medium-sized and small dendrites as
      well as in the dendritic spines. The CCK-LI axon terminals contain small round or
      pleomorphic vesicles. Sometimes they show a mixed population of clear and dense
      core vesicles. The immunoreactive terminal boutons establish typical asymmetrical
      synaptic contacts with dendritic spines, small or medium-sized dendrites. More
      rarely, the immunoreactive axon terminals perform symmetrical or intermediate
      synaptic contacts with proximal dendritic trunks or perikarya.

PMID- 8982809
TI  - Localisation of ionotropic glutamate receptor subunits, and gamma-aminobutyric
      acid (GABA) in the monkey amygdala--a double immunolabelling and electron
      microscopic study.
AB  - The distribution of ionotropic glutamate receptor subunits GluR1 and NMDAR1, and
      the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) was studied by
      immunocytochemistry, in the monkey amygdala. The basal and lateral nuclei
      contained a higher density of GluR1-positive neurons than the corticomedial and
      central groups of nuclei, and the accessory basal nucleus. A higher density of
      NMDAR1 immunopositive cell bodies was also present in the lateral nucleus,
      compared to the other nuclei of the amygdala. Large multipolar or fusiform
      projection neurons, and not small local circuit neurons were GluR1 or NMDAR1
      positive, and less than 0.5% of the GluR1-positive cells were double labelled for
      GABA. In contrast, almost all GluR1-positive neurons were also labelled for
      NMDAR1 in double labelled sections and vice versa. Electron microscopy also
      showed that GluR1- and NMDAR1-positive cells had distinctive ultrastructural
      features, compared with GABAergic cells, ant that there was very rare
      colocalisation, between GABA, and GluR1 or NMDAR1-positive cell bodies or
      dendrites. It is likely that not all projection neurons were GluR1 or NMDAR1
      positive, however, since GluR1 or NMDAR1-positive neurons were only 2-3 times as
      common as GABAergic cells, whereas it has been estimated that projection neurons
      outnumber GABAergic local circuit neurons by 4 to 1 (McDONALD and AUGUSTINE,
      1993; PITKANEN and AMARAL, 1994).

PMID- 8982810
TI  - Observations of non-stationarities in extracellular potassium dynamics within the
      gray matter neuropil during self-sustained SDs.
AB  - The chicken retina is an easily accessible piece of grey matter with a very
      prominent but simplified neuropil, the inner plexiform layer, which is formed
      mainly by synaptic terminals and Muller cell processes. In this preparation a
      self-sustained form of "spreading depression" waves, the circling wave, can be
      recorded for many hours. We have found that in some circling wave experiments
      extracellular potassium could display non-stationarities both, in the
      extracellular potassium wave dynamics during SDs, as well as in the intervals
      between successive waves. The implications of non-stationary behaviour for the
      understanding of the genesis of excitable states in the CNS are discussed in the
      paper.

PMID- 8982811
TI  - Larval development of tectal efferents and afferents in Xenopus laevis (Amphibia
      Anura).
AB  - The development of tectal connections in Xenopus laevis had been investigated
      using the degeneration technique to demonstrate the efferent pathways and the
      retrograde HRP transport to label the afferent pathways. Bilateral tectal
      efferents were present as soon as the beginning of metamorphosis. Ascending
      efferents originated from the anterior tectal part terminate in the secondary
      visual thalamic centres whereas the descending efferents coming from the
      posterior tectal part reached the tegmentum and the medulla oblongata. At this
      same time, the optic tectum already received secondary visual afferents
      originating in the ipsilateral pretectum and non-visual afferents from the
      ipsilateral semicircular torus and tegmentum. Some sparse bilateral isthmotectal
      connections were also present. Later, efferent pathways showed an increasing
      number of fibres whereas the sites of origin of afferents became more
      diversified: the dorsal thalamus, the suprachiasmatic area, the tegmental nuclei
      and in the medulla oblongata, the reticular and octavolateral areas sent
      bilateral projections to the optic tectum. At the end of metamorphosis, we noted
      ipsilateral olivotectal fibres and reciprocal connections between the tectum and
      the area of the Vth nerve. These last findings and the presence of the following
      direct projections, not previously reported in Anurans: the reciprocal
      connections between the tectum and the semicircular torus or the octavolateral
      area, underline the implication of the optic tectum in the multisensory (visual,
      acoustic, vibratory) integration elicited during the larval behavior. Also, the
      relations between the optic tectum and the lateral line system are particularly
      examined in the discussion.

PMID- 8982812
TI  - Quantitative changes in neuron and glial cells of neocortex following prenatal
      exposure to methylazoxymethanol.
AB  - The quantitative changes in neuron and glial cell density were analyzed in
      different cortical layers from frontal cortex of 3 and 12 months old mice exposed
      to Methylazoxymethanol (MAM) on embryonic day 15 (MAM 15) or 17 (MAM 17). An
      increase was found in glial cell density in all cortical layers from 3 months old
      MAM 17 compared to the age-matched controls. In particular, electron microscopic
      analysis showed that the only cells to increase in all cortical layers were the
      microglia cells. When the young and adult mice were compared it was noted that
      the glia increased significantly in all cortical layers of controls, whereas it
      did not change the older MAM 17. In the older MAM 15 the increase in glial
      density was similar to that observed in controls. No loss of cortical neurons was
      found between young and adult animals. In addition, the different trend of glial
      cell density between control and MAM 17 mice during aging was accompanied by a
      decline in the mean nuclear area in neurons of treated mice with respect to the
      controls. The hypothesis that MAM treatment seems to produce events similar to
      those normally occurring in aging finds support in the data of glial density and
      neuron size.

PMID- 8982813
TI  - Naturally occurring synapse degradation in the developing cerebellum of the
      mallard (Anas Platyrhynchos) and the Peking duck (Forma Domestica).
AB  - In order to analyze remodelling of junctions as component of adaptive mechanism
      in the developing avian cerebellum, a silver-staining technique was applied which
      is highly sensitive towards the detection of lysosomal aggregations (LA) in
      degrading synapses. LA was quantified in ducks at incubation ages from day 21 to
      28 and from hatching up to 32 days. In the mallard, LA increased gradually
      throughout the whole investigation period, while in the Peking duck LA showed a
      dramatic increase in the perihatching period followed by the beginning of a
      decline at about 3 weeks of age. In both species LA occurred initially in the
      superficial molecular layer prehatching followed by a succession of degradative
      events down to the granular layer. LA dynamics thus coincide with the outside-in
      proliferation and differentiation of granule cells during advanced cortical
      histogenesis. Light microscopy of Epon sections impregnated with silver indicated
      that granule and Purkinje cell contacts were the center of LA dynamics. Electron
      microscopy confirmed that synapse degradation occurred predominantly with
      presynaptic elements of climbing, parallel and mossy afferents. As illustrated by
      the structural dynamics, maturation of cerebellar circuitry passes through a
      period of unbalanced synaptogenesis posthatching. Remarkably, the ongoing
      "critical period" of synaptogenesis in the mallard provides the opportunity for
      more differentiated behavioral pattern formation in the wild as compared to the
      domestic duckling.

PMID- 8982814
TI  - Distribution of glycine and GABA immunoreactivities in the cochlear nucleus:
      quantitative patterns of putative inhibitory inputs on three cell types.
AB  - Postembedding immunocytochemistry was used to compare the distribution of GABA
      and glycine immunoreactive labelling in the cochlear nucleus, in particular the
      number of immunolabeled synaptic boutons apposing the cell body profiles of three
      major neuronal types. The proportions and absolute numbers of glycine
      immunoreactive puncta were greatest on fusiform cell body profiles. Glycine
      immunoreactive puncta also predominated on spherical cell body profiles, although
      GABA immunoreactive boutons were more abundant than on fusiform cells. Octopus
      cell body profiles were apposed by the fewest immunoreactive puncta. Puncta
      colabeled for glycine and GABA were frequently observed on all three cell types.
      These findings suggest that each major cell type possesses a distinct pattern of
      glycinergic and GABAergic input, with glycinergic input predominating. Since both
      tuberculoventral and cartwheel neurons were immunolabeled and are known to
      project intrinsically, it is clear that a large percentage of glycinergic and
      GABAergic input to cochlear nucleus neurons originates from intrinsic sources.

PMID- 8982819
TI  - The intestinal uptake of particles and the implications for drug and antigen
      delivery.
AB  - A number of researchers from different scientific disciplines have independently
      described the uptake of a variety of particulates across the gastrointestinal
      tract in animal models. The reports of particle uptake are briefly reviewed and
      the alternative mechanisms and proposed sites of uptake are discussed. Following
      these observations, some researchers have exploited the phenomenon of particulate
      uptake by using microparticles and nanoparticles as oral delivery systems for
      active agents, such as drugs and vaccines. The potential use of particulate
      carrier systems as drug and vaccine delivery systems is also briefly discussed.

PMID- 8982820
TI  - The influence of age and particle number on absorption of polystyrene particles
      from the rat gut.
AB  - The bioavailability of polystyrene particles (1 microns) labelled with FITC (3M
      Company, Dusseldorf) was tested in rats after enteral administration. Since
      macromolecules and particles are preferentially transported in the lymph, the
      number of particles was counted in the lymph of the thoracic duct over a 6 h
      period. Uptake in young rats (6-8 wk) was compared with that in 5 and 9 mo
      animals. Young animals absorbed only 87 particles whereas a marked increase in
      the uptake of particles was observed in 5 mo animals (up to 775) but there was a
      decrease to 518 particles in older animals (9 mo). This number of particles is
      the total number of the entire output of the thoracic duct lymph over a 6 h
      period. In individual animals this number showed a considerable fluctuation over
      time. The volume of the collected lymph fluid was relatively constant (3.5 +/-
      0.5 ml) in all animals. The bioavailability of the particles in the lymph was
      also influenced by the applied dose of particles. After intraduodenal
      administration of 3.7 x 10(5) particles only 18 particles could be found in the
      lymph. Increasing the dose to 3.7 x 10(7) particles raised the number of
      particles in the lymph to 116. The highest dose of 3.7 x 10(9) was correlated
      with the greatest absorption, 775 particles being found in the lymph. The uptake
      of particles from the gut thus depends on different factors including the age of
      the animal and the number of applied particles.

PMID- 8982821
TI  - Particle uptake and translocation across epithelial membranes.
AB  - Oral delivery of drugs and vaccines has many advantages over other routes of
      administration. For example, for vaccination, enteric delivery may result in the
      induction of a mucosal immune response against pathogens which colonise and
      invade the mucosa. However, the oral delivery of peptide or protein drugs or
      antigens is beset with problems, such as gastrointestinal breakdown of labile
      molecules, low level of macromolecular absorption and, for vaccines, the poor
      immune response usually elicited by orally administered soluble antigens.
      Investigations are therefore in progress to develop means of increasing
      intestinal absorption and decreasing digestion of orally administered molecules.
      Molecules can be incorporated into biodegradable microparticles to reduce the
      effect of gut secretions and to enable the absorption of bioactive agents in an
      unaltered form. The uptake of microparticulates through the gut wall is accepted
      as a true biological phenomenon but the mechanism and route of uptake have not
      been established. Furthermore, in general, only small numbers of microparticles
      are translocated across epithelial membranes, possibly making these systems
      inappropriate for drug or vaccine delivery. This paper reviews particle uptake
      across the gastrointestinal tract and describes studies carried out to determine
      whether a humoral response can be elicited following oral administration of an
      antigen associated with biodegradable poly(DL lactide-coglycolide)
      microparticles. The use of lipid delivery vehicles to enhance microparticle
      uptake and the selective transport of microspheres across M cells is also
      described.

PMID- 8982822
TI  - Intestinal absorption of PLAGA microspheres in the rat.
AB  - Rhodamine B-labelled poly (DL-lactide-co-glycolide) (PLAGA) microspheres of 2
      different sizes, 1-5 microns and 5-10 microns, were administered as a single dose
      (1.44 x 10(9) and 1.83 x 10(8) particles, respectively) into the ileal lumen of
      adult rats. The content of rhodamine in the mesenteric vein and ileal lumen was
      analysed periodically from 10 min to 48 h as well as the distribution of
      microspheres in the intestinal mucosa and various other tissues. The
      concentration of rhodamine decreased progressively in the intestinal lumen and
      was negligible after 24 h. The number of microspheres in the mesenteric vein
      increased rapidly and reached a maximum after 4 h whatever the size of the
      particles. It then decreased progressively, but more rapidly with microspheres >
      5 microns than with microspheres < 5 microns. The absorption efficiency was low
      for the former batch (about 0.11% of the administered dose) and higher for the
      latter (about 12.7%). The intraileal administration of free rhodamine B was
      followed by intense labelling of the epithelial cells and basement membranes in
      mesenteric lymph nodes, spleen, kidney and liver. PLAGA microspheres mainly
      crossed the intestinal mucosa at the site of Peyer's patches where microspheres
      of < 5 microns appeared after 3 h. Microspheres > 5 microns were retained in the
      ileal lumen. A few small microspheres were occasionally observed in the
      epithelial cells. Only the smallest particles were recovered in the liver, lymph
      nodes and spleen while basement membranes were always labelled. It is concluded
      that PLAGA microspheres could be useful for the oral delivery of antigens if
      their size is between 1 and 5 microns.

PMID- 8982823
TI  - Nanoparticles and microparticles for drug and vaccine delivery.
AB  - Nanoparticles are polymeric particles in the nanometer size range whereas
      microparticles are particles in the micrometre size range. Both types of particle
      are used as drug carriers into which drugs or antigens may be incorporated in the
      form of solid solutions or solid dispersions or onto which these materials may be
      absorbed or chemically bound. These particles have been shown to enhance the
      delivery of certain drugs across a number of natural and artificial membranes. In
      addition, the particles were shown to accumulate in areas of the intestine that
      appear to be the Peyer's patches. Possibly because of the combination of both
      effects these particles were able to significantly improve the bioavailability of
      some drugs after peroral administration in comparison with solutions. Recently
      nanoparticles coated with polysorbate 80 enabled the passage of small peptides
      and other drugs across the blood-brain barrier and the exhibition of a
      pharmacological effect after intravenous injection. Without the use of this type
      of nanoparticles the drugs did not cross this barrier and yielded no effect.

PMID- 8982825
TI  - Targeting of drugs and delivery systems to specific sites in the gastrointestinal
      tract.
AB  - Particle uptake and translocation occur at specific sites in the gastrointestinal
      tract. Several drugs are also absorbed from solution only through narrow
      "windows' in the small intestine. In these circumstances, optimum therapeutic
      benefit would be obtained if the active agent was targeted to the appropriate
      site in the gastrointestinal tract. Targeting relies on exploiting a unique
      feature of the intended site and protecting the active agent until it reaches
      that site. This minireview highlights the problems in achieving site specificity
      in the gastrointestinal tract and examines possible solutions to the problem for
      2 regions, the stomach and the colon.

PMID- 8982824
TI  - Targeting to intestinal M cells.
AB  - The specialised, antigen-transporting, epithelial M cells in the follicle
      associated epithelium (FAE) overlying gut-associated lymphoid tissues constitute
      the primary target for oral delivery of vaccines. Our studies have shown that
      polystyrene microspheres selectively bind to, and are efficiently transcytosed
      by, rabbit Peyer's patch M cells in closed intestinal loops. Binding of
      biodegradable poly(DL-lactide-co-glycolide) microspheres to rabbit Peyer's patch
      FAE is an order of magnitude lower than that of polystyrene microspheres.
      Although poly(DL-lactide-co-glycolide) microspheres are not selectively targeted
      to M cells, a high proportion of those which bind to M cells are transcytosed,
      supporting the potential of such microspheres as vehicles for oral vaccine
      delivery. Comparison of the binding of polystyrene microspheres by murine FAE
      revealed this to be markedly less extensive than by rabbit FAE. These data
      demonstrate that microsphere binding by M cells depends on the surface properties
      of both cells and microspheres and suggest that surface modification may enhance
      the efficacy of microsphere delivery vehicles. One such approach is the
      incorporation of molecules with inherent binding specificity for M cells. Lectin
      binding studies have revealed that M cells exhibit pronounced regional and
      species variation in glycoconjugate expression. In murine intestine, certain
      lectins bind selectively to M cells either in Peyer's patches or caecum, or at
      both sites. Selective targeting to, and transcytosis of, lectin-conjugates by M
      cells in ligated segments of murine intestine have also been demonstrated. While
      several lectins display strong selectivity for rabbit caecal M cells, none to
      date have been identified with specificity for rabbit or rat Peyer's patch M
      cells. Knowledge of human M cells is limited and no lectin has yet been
      identified with specificity for these cells. However, at least one lectin
      exhibits binding specificity for FAE in the human ileum. In the future, knowledge
      of the regional patterns of M cell carbohydrate expression within a species may
      allow lectins to be utilised to target selectively antigenic material to the
      mucosal immune system at specific locations.

PMID- 8982826
TI  - The assessment of doses and effects from intakes of radioactive particles.
AB  - The behaviour of radionuclides after entry into the body and the radiation doses
      received by individual tissues depend on the chemical nature of the element, the
      physicochemical form of the intake, the radioactive half-life of the isotope and
      the type and energy of the emissions. Ingestion of radionuclides in insoluble
      particles will result in radiation doses being delivered to tissues of the
      gastrointestinal (GI) tract; other tissues will also be irradiated by nuclides
      with penetrating photons emissions (gamma) but doses may be largely confined to
      the GI tract for charged particle emissions (alpha, beta). Ingestion of more
      soluble forms will lead to greater absorption to blood and deposition in other
      tissues and therefore may result in greater doses to other tissues. Similar
      considerations apply to inhaled material and to the entry of radionuclides
      through cuts or wounds. For ingested materials, including particles, more
      information is needed on uptake and retention in intestinal tissues and
      consequent doses to sensitive cells, particularly for alpha emitters. There has
      been concern that the pattern of distribution of activity throughout irradiated
      tissues may influence the extent of damage, particularly for alpha emitters
      because of the localised deposition of energy and their greater relative
      biological effectiveness compared with beta/gamma emitters. Aggregation of
      activity has the potential to result in greater acute tissue damage and has been
      shown, for example, to result in focalised pneumonitis and fibrosis in the lung
      and ulceration of the skin. The main long-term effect of irradiation of tissues
      is the induction of malignant change, although hereditary disease may also be of
      concern following irradiation of the gonads. There are only limited data
      available to compare the effect on cancer induction of heterogeneous and
      homogeneous irradiation of tissues. However, the available information, for
      irradiation of the lung, skin or liver, indicates that in general nonuniform
      alpha irradiation from radioactive particles is no more hazardous, and may be
      less hazardous, than if the same activity is uniformly distributed.

PMID- 8982827
TI  - Qualitative investigation of uptake of fine particle size microcrystalline
      cellulose following oral administration in rats.
AB  - A subchronic toxicity study was conducted to evaluate the potential toxicological
      effects associated with intestinal translocation of a special fine particle size
      (median particle size 6 microns) microcrystalline cellulose (MCC). Four groups of
      Sprague-Dawley rats (20/sex/group) received either 0 (control), 500, 2500 or 5000
      mg/kg/day MCC (25% w/v in tap water) daily by oral gavage for 90 d. At study
      termination, organs and tissues from high-dose and control animals, including
      multiple sections of intestine with gut-associated lymphoid tissue, were
      processed for light microscopy with subsequent examination under polarised light
      for the presence of birefringent MCC particles. None were observed in any tissue
      examined. No toxicologically significant effects or lesions were found in any
      other parameter or organ evaluated. The 'no observed adverse effect level'
      (NOAEL) for toxicological effects was greater than 5000 mg/kg/day MCC, which was
      the highest dosage tested. These results further verify the safety of commercial
      MCC products for use in food and pharmaceutical applications.

PMID- 8982829
TI  - Influence of immunoglobulin and interleukin 2 on the translocation of
      microorganisms from gut into blood.
AB  - The aim of this study was to influence the translocation of microorganisms and
      endotoxin from the gut of septic rats by the intravenous (i.v.) administration of
      immunoglobulin and interleukin 2. Acute infection was induced in all animals by
      an intraperitoneal bacterial challenge of 2 x 10(6) microorganisms (Ps.
      aeruginosa, E. coli, Kleb. pneumoniae). Immediately after the bacterial challenge
      control animals were given albumin i.v. whereas the experimental groups were
      given immunoglobulin or interleukin 2. A significant reduction of bacteria in the
      plasma of rats was observed in immunoglobulin treated animals (10,000 CFU/ml vs
      450 CFU/ml). This was accompanied by an increase of plasma endotoxin of nearly
      100% within the first 2 h. Interleukin 2 essentially did not change the bacterial
      count in comparison with albumin-treated control animals but reduced the
      endotoxin level in plasma up to tenfold. It is concluded that both
      immunoglobulins and interleukin 2 are involved in severe infections. Whereas
      immunoglobulins reduce bacterial translocation, interleukin 2 stimulates the
      elimination of endotoxin.

PMID- 8982830
TI  - Gastrointestinal uptake and translocation of microparticles in the streptozotocin
      diabetic rat.
AB  - Uptake and translocation of particulates across the mucosal barrier of the
      gastrointestinal (GI) tract is now generally recognised but the effect of
      pathophysiologically induced changes on this process is less well established.
      This study evaluated the effect of diabetes mellitus on GI absorption of
      particles, comparing particle localisation and particle loading in different
      microanatomical sites of the primary organ (small intestine) and possible
      particle translocation pathways to selected secondary organs (mesenteric lymph
      nodes, liver, spleen) in normal and streptozotocin-induced diabetic animals.
      Fluorescent polystyrene latex particles (approximately 2 microns diameter) were
      fed orally to young adult Sprague-Dawley rats and quantitative bulk tissue and
      morphological techniques used to chart particle transit across the small
      intestine to secondary organs 0.5 h postadministration. In the normal animal,
      epifluorescence and confocal laser scanning microscopy provided confirmatory
      evidence for particle absorption within the primary organ and transport to other
      sites in the body. By contrast, in the diabetic animal, particle translocation
      and peripheral distribution were reduced with approximately 30% decrease in
      particle loading in the epithelial/nonepithelial tissue compartments. This could
      be a consequence of gastric retention and altered intestinal motility and
      permeability which are known to be associated with diabetes.

PMID- 8982831
TI  - Bacterial translocation and gut microflora in obstructive jaundice.
AB  - Bacterial translocation from the gut is implicated in the pathophysiology of
      complications associated with obstructive jaundice. Absence of intraluminal bile
      salts and their antiendotoxic effects may result in overgrowth of bacteria,
      promoting bacterial translocation. The large bowel is the largest source of gram
      negative bacteria but the small bowel is more permeable. This study investigated
      the effect of obstructive jaundice on bacterial translocation and on the
      indigenous luminal microflora at 3 sites in the gastrointestinal tract.
      Significant bacterial translocation was demonstrated following 7 d of bile duct
      ligation compared with control or sham operated groups. A qualitative disturbance
      of the caecal indigenous microflora was demonstrated in jaundiced rats. There was
      no 'site-to-site' variation in the indigenous microflora at the 3 intestinal
      sites studied. We conclude that experimental obstructive jaundice for 1 wk
      promotes bacterial translocation without significant quantitative disturbance of
      the intestinal microflora in the small intestinal or caecum.

PMID- 8982828
TI  - The relationship between gut-derived bacteria and the development of the multiple
      organ dysfunction syndrome.
AB  - Abnormal colonisation, infections of gut origin and bacterial translocation are
      all signs of gut failure that have been hypothesised as being implicated in the
      pathogenesis of the multiple organ dysfunction syndrome (MODS). We have
      summarised published experimental and clinical studies that have tried to
      correlate the occurrence or prevention of these phenomena with the development of
      MODS. We conclude that in some patients loss of intestinal barrier function or
      the onset of infection precedes the development of MODS. In other patients,
      however, this relationship is not so clear and it seems that these are epiphenoma
      of critical illness and may reflect a failure of the host's immune and mechanical
      defence systems. The causal relationship between these phenomena and the
      development of MODS is complex and needs further clarification.

PMID- 8982833
TI  - Lines of action and moment arms of the major force-bearing structures crossing
      the human knee joint: comparison between theory and experiment.
AB  - Lines of action and moment arms in the sagittal plane of the major tension
      bearing structures at the knee joint were calculated using an anatomy-based
      mathematical model and compared with experimental measurements reported by Herzog
      & Read (1993). The mobility of the model tibiofemoral joint was controlled by a
      sagittal plane 4-bar linkage consisting of the femur, tibia and the 2 cruciate
      ligaments while the knee extensor mechanism was characterised by a patellofemoral
      joint model. Model parameters were obtained from previous cadaveric and MRI
      studies. The theoretical results compare well with the published experimental
      measurements which suggests that, with relatively simple measurements, the model
      was able to reproduce major features of the natural knee joint and provide
      necessary information for further mechanical analysis.

PMID- 8982832
TI  - Immunohistochemical study of amoeboid microglial cells in fetal rat brain.
AB  - The present study examined the expression of different antigens in amoeboid
      microglial cells (AMC) in fetal rat brain extending from 12 to 20 d
      postconception (E12-E20) using a panel of monoclonal antibodies which recognised
      the major histocompatibility complex (MHC) class I (OX-18) and class II (OX-6)
      antigens, leucocyte common antigen (OX-1), CD4 receptor (OX-35), complement type
      3 receptor (OX-42) or macrophage antigens of unknown function (ED1 and ED2). Of
      the above-mentioned antigens, ED1 and ED2-labelled AMC were observed in the
      neuroepithelia as early as embryonic day 12 (E12); other antigens were not
      detected at this stage. At E14, except for MHC class I antigen, all other
      antigens were expressed by AMC distributed predominantly in the developing white
      matter. At E16, AMC in the intermediate zone lateral to the striatum were endowed
      with all the above-mentioned antigens including MHC class I. At E18, the
      immunoreactivities of AMC stained with OX-6, OX-18, OX-35 and OX-42 antigens were
      noticeably reduced when compared with those cells at E16. At E20, amoeboid
      microglial cells exhibited full complement of antigen expression similar to those
      cells at E16; some of the labelled cells emitted a variable number of cytoplasmic
      processes. It is suggested that the successive and differential expression of
      various macrophage related antigens on AMC in fetal brain is related to the
      specific requirement of local environment in different stages of development.

PMID- 8982834
TI  - Functional anatomy of the radial sesamoid bone in the giant panda (Ailuropoda
      melanoleuca).
AB  - The function of the radial sesamoid bone (RS) in the giant panda (Ailuropoda
      melanoleuca) was examined by macroscopic study of RS-related bones and muscles.
      The RS was observed to be connected to the scapholunar and the 1st metacarpal
      bones. A joint cavity was present between the proximal surface of the RS and the
      distal area of the scapholunar bone but the RS possessed a fibrous joint
      connecting it to the proximal radial surface of the 1st metacarpal bone. It is
      suggested that the RS possesses no substantial abductor-adductor function as the
      articulation between the RS and the 1st metacarpal bone (FM) seems not to permit
      flexible movement of the RS. The RS may be a supporting process opposite the
      digits in the palm when the animal flexes its 5 digits to grip objects, but it is
      not an active grasping apparatus. In the muscular system, abductor pollicis
      longus provided strong tendons to the RS as an RS-abductor, whereas the abductor
      pollicis brevis, opponens pollicis and aponeurosis palmaris were well developed
      as an RS-adductor muscle group. Observation of RS articulations, however, showed
      that the muscles do not provide appreciable abduction-adduction actions for the
      RS.

PMID- 8982835
TI  - Tendon cells in vivo form a three dimensional network of cell processes linked by
      gap junctions.
AB  - Tendons respond to mechanical load by modifying their extracellular matrix. The
      cells therefore sense mechanical load and coordinate an appropriate response to
      it. We show that tendon cells have the potential to communicate with one another
      via cell processes and gap junctions and thus could use direct cell/cell
      communication to detect and/or coordinate their load responses. Unfixed
      cryosections of adult rat digital flexor tendons were stained with the
      fluorescent membrane dye DiI to demonstrate cell shape. Similar sections were
      immunolabelled with monoclonal antibodies to rat connexin 32 or connexin 43 to
      demonstrate gap junctions and counterstained with propidium iodide to show
      nuclei, or the membrane stain DiOC7 to show cell membranes. Sections were
      examined with a laser scanning confocal microscope and 3-dimensional
      reconstructions were prepared from optical section series to demonstrate cell
      shape and the position of connexin immunolabel. Cells had a complex
      interconnected morphology with gap junctions at points of contact with other
      cells. Cell bodies contained the nucleus and extended broad flat lateral cell
      processes that enclosed collagen bundles and interacted with similar processes
      from adjacent cells. They also had long thin longitudinal processes interacting
      with the cell process network further along the tendon. Connexin 43 occurred
      where cell processes met and between cell bodies, whereas connexin 32 was only
      found between cell bodies. The results indicate the presence of a 3-dimensional
      communicating network of cell processes within tendons. The intimate relationship
      between cell processes and collagen fibril bundles suggests that the cell process
      network could be involved in load sensing and coordination of response to load.
      The presence of 2 different types of connexins suggests that there could be at
      least 2 distinct communicating networks.

PMID- 8982836
TI  - Skeleton pattern and joint formation in chorioallantoic grafts lacking the
      anterior or posterior necrotic zones.
AB  - Skeletal pattern and joints formation were examined in chick limb bud grafts
      using the chorioallantoic grafting method which enabled the separation of the
      limb bud from the body wall and also restricted the influence of some of the
      morphogenetic zones of the limb. The embryonic chick limb buds from the
      experimental group were transplanted without the prospective anterior necrotic
      zone (ANZ) or the posterior necrotic zone (PNZ). Transplants with intact limb bud
      material served as the control group. Elimination of the ANZ or PNZ mainly
      affected the skeleton of the zeugopod and elbow joint. Most grafts lacking the
      ANZ or PNZ showed fusion of the ulna and radius and complete regression of the
      elbow joint. The most common abnormality was fusion of the humerus, ulna and
      radius into a single cartilaginous block which was rarely observed in control
      grafts. As the separation of the ulna and radius depends on cell death in the
      "opaque patch', it is likely that mechanical elimination of the ANZ or PNZ
      suppressed cell death in this zone and caused a typical fusion in the zeugopod
      skeleton and elbow joint and growth retardation in grafts lacking the ANZ or PNZ.

PMID- 8982837
TI  - A histochemical study of the distribution of lectin binding sites in the
      developing branchial area of the trout Salmo trutta.
AB  - A histochemical study of the branchial area of brown trout embryos from 35 to 71
      d of incubation is reported. A battery of 6 different horseradish peroxidase
      labelled lectins, the PAS reaction and Alcian blue staining were used to study
      the distribution of carbohydrate residues in glycoconjugates along the pharyngeal
      and branchial epithelia. Con A and WGA reacted at every site of the branchial
      region thus showing the ubiquitous presence of alpha-D-mannose and N-acetyl-D
      glucosamine. WGA, DBA and SBA were good markers for the hatching gland cells
      (HGCs) and mucous cells. Other lectins, such as PNA and UEA I, reacted only for a
      short time at some sites during the considered period of incubation. From 35 d
      until posthatching stages, a manifest strong reaction was noted both in the
      dorsal epithelium of branchial arches and the HGCs as shown by SBA reactivity.
      This may be significant with regard to the controversial origin of HGCs, which is
      thought to be endodermal.

PMID- 8982838
TI  - Distribution of alpha-vascular smooth muscle actin in the smooth muscle cells of
      the gastrointestinal tract of the chicken.
AB  - Immunoreactivity specific for alpha-vascular smooth muscle actin (ASMA) was
      examined in the enteric smooth muscle cells along the entire length of the
      gastrointestinal tract of the chicken. Specificity for gamma-smooth muscle actin
      (GSMA) and desmin was also examined. All smooth muscle layers, i.e. the
      muscularis mucosae, and the circular and longitudinal muscle layers, showed
      immunoreactivity specific for GSMA and desmin throughout the gastrointestinal
      tract whereas immunoreactivity for ASMA differed between regions and muscle
      layers. In the oesophagus and crop, immunoreactivity for ASMA was observed in the
      muscularis mucosae and the inner and outer muscle layers, together with staining
      for GSMA and desmin. In the proventriculus, immunoreactivity for ASMA was
      observed in all smooth muscle cells in the inner layer of the muscularis mucosae
      and the longitudinal muscle layer. In the outer layer of the muscularis mucosae,
      immunoreactivity for ASMA on smooth muscle cells was observed on the luminal side
      and decreased in the serosal direction. In the intermediate muscles,
      immunoreactivity for ASMA was observed in the luminal portion, the intensity of
      staining decreasing gradually in the serosal direction. In contrast to the
      intermediate muscles, the latter muscles were negative for ASMA. In the pyloric
      region, the outer part was weakly immunopositive, while the inner part was
      intensely positive. In the small and large intestines, the muscularis mucosae and
      the longitudinal muscle layer were positive for ASMA. The outer part of the
      circular muscle layer was immunonegative for ASMA whereas the inner part was
      positive. The complex structure and contractile functions of each organ and
      muscle layers may be related to the difference patterns of expression of ASMA
      molecules in the smooth muscle cells.

PMID- 8982839
TI  - An ultrastructural study of the development of the chicken perineurial sheath.
AB  - Three phases of perineurial development were recognised in the chicken sciatic
      nerve: (1) an early primitive phase during which the embryonic perineurium
      appeared to organise from the surrounding mesenchyme; (2) an intermediate phase
      of differentiation with the formation of a multilayered cellular network around
      the Schwann cell-axon complexes, and (3) a final phase of maturation during which
      the perineurial sheath showed features correlating with those of a functional
      barrier. Our observations support a mesenchymal origin for the perineurium rather
      than a schwannian derivation with clear separation of these 2 cell populations
      during all stages of development. Although the embryonic perineurial cells
      initially showed a fibroblast-like appearance, distinctive features of
      perineurial differentiation were present as early as 5 1/2 days (d) (Hamburger &
      Hamilton stage 28 embryo). Perineurial differentiation appeared to be intimately
      associated with developmental events in the Schwann cell-axon complexes,
      particularly during the period of most active Schwann cell proliferation. It is
      proposed that factors released by the Schwann cell-axon complexes during this
      period may be responsible for perineurial differentiation and organisation from
      the surrounding mesenchyme. The presence of endoneurial blood vessels following
      the appearance of perineurial basal lamina at 17 d (stage 43) suggested the
      emergence of a perineurial barrier. A perineurial architecture and cytological
      fine structure comparable to that of the adult animal was, however, only observed
      in the 10 d-old-chick.

PMID- 8982840
TI  - Light microscopic histochemical and immunohistochemical localisation of sulphated
      glycosaminoglycans in the rooster comb and wattle tissues.
AB  - Comb and wattle tissues, which consist of layers of epidermis, dermis and central
      connective tissue, are known to contain sulphated glycosaminoglycans (GAGs)
      including dermatan sulphate and chondroitin sulphate-dermatan sulphate
      copolymers. Little is known about distribution of these CAGs in each tissue. The
      objective of this study was to localise sulphated GAGS in the comb and wattle
      tissues from mature roosters. Monoclonal antibodies 6D6, CS-56 and AH12 specific
      to dermatan sulphate proteoglycan (decorin), chondroitin sulphate and keratan
      sulphate, respectively, were used. In both tissues, 6D6 epitope was found to be
      more concentrated in the superficial layer of dermis and the central connective
      tissue than in the intermediate layer of dermis containing fibromucoid tissue.
      The staining pattern for 6D6 epitope was similar to that for collagen fibres. In
      contrast, CS-56 epitope was uniformly distributed in most parts of the dermis and
      the central connective tissue. The stratum germinativum in the epidermis was the
      major tissue showing positive staining with AH12, haematoxylin and safranin-O.

PMID- 8982841
TI  - Development of the ovary in the brushtail possum Trichosurus vulpecula
      (Marsupialia).
AB  - The urogenital region of 25 fetuses and 75 pouch young, ranging in age from
      newborn to 103 days (d) in development, was examined in serial histological
      sections. The rete ridges formed the anterior extensions of the gonadal ridges
      and gave rise to the rete system and gonads respectively. Sexual differentiation
      of the ovary commenced 2.5 d after birth, when 2 cell types appeared: the larger
      of these then clumped together to form the medullary cords, while the smaller
      cells gave rise to the stroma. Primordial germ cells were still migrating,
      dividing and populating the peripheral gonadal regions on d 8. Cortex and medulla
      were distinguishable by d 12, when a thick fibrous zone separated them. The
      cortex was augmented by cells from the mesothelium. The rete ovarii developed
      from cell condensations within the rete ridges, made secondary contact with the
      mesonephroi and penetrated the ovaries but did not contribute to the granulosa
      cells. It is concluded that, contrary to the situation in most eutherians, in
      Trichosurus, as in other marsupials examined, the mesonephros does not contribute
      to rete formation, or to the granulosa cells, which appear to arise from the
      medullary cords.

PMID- 8982842
TI  - The apical caecal diverticulum of the chicken identified as a lymphoid organ.
AB  - A peculiar structure, observed as a dome-like protrusion at the apex of the
      caecum, was investigated macroscopically and histologically in healthy White
      Leghorn chickens. It was hemispheric or spherical in shape and as it consisted of
      a lumen with a wall occupied by lymphoid tissue, this structure was designated
      the apical caecal diverticulum (ACD). ACD were detected in 25.2% of examined
      chickens and had a mean diameter and height of 1.9 mm and 1.2 mm respectively.
      Histologically, both the lamina propria mucosae and the submucosa of ACD
      consisted of well developed aggregated lymphoid nodules. Each nodule was covered
      by follicle-associated epithelium which contained cells resembling M cells. Some
      secondary nodules extended into the subserosa. The muscularis mucosae and the
      stratum circulae of the tunica muscularis disappeared near the entrance to ACD.
      The stratum longitudinale also gradually decreased in thickness around the
      entrance, becoming an extremely thin layer in the diverticulum wall. At the
      caecal apex, each stratum of the tunica muscularis was thinner than in the caecal
      body and separated into several muscle bundles. These bundles were occasionally
      displaced by developed lymphoid nodules, causing them to protrude into the
      subserosa. The high frequency of ACD suggests that caecal apex may be sites for
      immunological surveillance in the chicken caecum. In addition to the intense and
      frequent antiperistalsis at the apex suggested by Yasukawa (1959), possible
      causes for the formation of ACD included (1) the fragility of the tunica
      muscularis at the ACD, and (2) the local removal of the physical supporting
      structures by the development of lymphoid nodules.

PMID- 8982843
TI  - Neurocranial morphology as determined by asymmetries of the skull base.
AB  - The goal of the current study was to provide an easy to use criterion to diagnose
      neurocranial asymmetries. An anatomical survey of the external aspect of the
      skull base was planned to correlate with radiological studies. In a sample of 239
      skulls, variations of the angular relationship between the structures seen on a
      basilar view of the cranium were analysed. An anterior and a posterior transverse
      line were plotted with respect to the midline. Departures from 90 degrees to the
      midline for either of the transverse lines were less than 5 degrees in normal
      skulls, between 5 degrees and 7 degrees in skulls classed by independent
      inspection as asymmetric, and more than 7 degrees in obviously malformed skulls.

PMID- 8982845
TI  - Ultrastructural identification of Langerhans cells in normal feline epidermis.

PMID- 8982844
TI  - Endoanal MRI of the anal sphincter complex: correlation with cross-sectional
      anatomy and histology.
AB  - The purpose of this study was to correlate the in vivo endoanal MRI findings of
      the anal sphincter with the cross-sectional anatomy and histology. Fourteen
      patients with rectal tumours were examined with a rigid endoanal MR coil before
      undergoing abdominoperineal resection. In addition, 12 cadavers were used to
      obtain cross-sectional anatomical sections. The images were correlated with the
      histology and anatomy of the resected rectal specimens as well as with the cross
      sectional anatomical sections of the 12 cadavers. The findings in 8 patients, 11
      rectal preparations, and 10 cadavers, could be compared. In these cases, there
      was an excellent correlation between endoanal MRI and the cross-sectional cadaver
      anatomy and histology. With endoanal MRI, all muscle layers of the anal canal
      wall, comprising the internal anal sphincter, longitudinal muscle, the external
      anal sphincter and the puborectalis muscle were clearly visible. The levator ani
      muscle and ligamentous attachments were also well demonstrated. The perianal
      anatomical spaces, containing multiple septae, were clearly visible. In
      conclusion, endoanal MRI is excellent for visualising the anal sphincter complex
      and the findings show a good correlation with the cross-sectional anatomy and
      histology.

PMID- 8982846
TI  - A new simple method for conservation and demonstration of body sections for
      teaching clinically oriented courses in gross anatomy.

PMID- 8982847
TI  - A retrocaval right testicular artery passing through a hiatus in a bifid right
      renal vein.

PMID- 8982848
TI  - Bilateral superficial radial artery at the wrist associated with a radial origin
      of a unilateral median artery.

PMID- 8982849
TI  - Identification of interleukin-6 as a factor that induces neurite outgrowth by
      PC12 cells primed with NGF.
AB  - We have screened for a factor that induces neurite outgrowth by PC12 cells only
      after NGF pretreatment in the supernatants of 38 transformed cell lines, finding
      three positive clones. The factor showing the strongest activity was purified and
      identified as IL6. In this NGF-IL6 system, the process of neurite outgrowth by
      PC12 cells can be separated into NGF-dependent and IL6-dependent steps. The IL6
      dependent step requires RNA synthesis, suggesting that IL6 induces new gene
      expression depending on NGF-priming. These findings suggest that the gene
      expression during the differentiation process is regulated by at least two
      signals.

PMID- 8982851
TI  - Unfolding and refolding of the N-terminal fragments of staphylococcal nuclease R
      in guanidine hydrochloride.
AB  - The conformational and activity changes of a family of peptide fragments of
      staphylococcal nuclease R, which extend from residues -6 to 102, -6 to 110, -6 to
      121, -6 to 135, and -6 to 141, during unfolding and refolding in different
      concentrations of guanidine hydrochloride have been studied. The studies indicate
      that the conformational stability in guanidine hydrochloride solution of the N
      terminal fragment increases with increasing chain length, and that interaction
      and recognition between amino acid residues which are related to formation of the
      native conformation also increase with growth of the peptide chain, but such
      interaction becomes effective only when the polypeptide chain reaches a certain
      length. The changes in conformation and catalytic activity of the N-terminal
      fragments during unfolding and refolding demonstrate that conformational
      adjustments are necessary during chain elongation to generate the native
      conformation of a biologically active protein.

PMID- 8982850
TI  - Further study on association of 5SrRNA-L5 protein complex and methionyl-tRNA to
      methionyl-tRNA synthetase in the macromolecular aminoacyl-tRNA synthetase
      complex.
AB  - To obtain direct evidence for the attachment of 5SrRNA-ribosomal L5 protein
      particles (5SRNP) and methionine-tRNA (tRNA(met)) to methionyl-tRNA synthetase
      (MetRS) in the macromolecular aminoacyl-tRNA synthetase (ARS) complex of rat
      liver, a MetRS-5SRNP-tRNA(met) complex was dissociated from the macromolecular
      ARS complex fraction by n-octyl-beta-D-glucoside (Method I) or by omega
      aminooctyl agarose (Method II) chromatography. The dissociated MetRS complex
      fraction was purified by gel filtration followed by tRNA-Sepharose chromatography
      using partially purified tRNA(met) in Method I, and by hydrophobic interaction
      chromatography in Method II. In both methods, final Superdex200 chromatography
      showed that MetRS activity was present in the region corresponding to the
      molecular weight of the MetRS-5SRNP-tRNA(met) complex (M(r) 200,000). One main
      protein band corresponding to the molecular weight of MetRS was observed on SDS
      PAGE of the final product, which was concentrated by lyophilizing after dialysis
      against water. Using serum albumin as an inhibitor of adhesion of L5 to the
      microconcentrators which was used to concentrate the final product, a distinct L5
      band was detected on SDS-PAGE, the intensity of which was comparable to that of
      the MetRS band. Northern blot analysis of RNA prepared from the tRNA-Sepharose
      fraction showed the presence of 5SrRNA. Dot blot analysis using an antibody
      against ribosomal protein L5 showed that L5 was present in the Superdex200
      fractions prepared by both methods. The MetRS specific activities in MetRS
      complex fractions incubated without tRNA increased during the purification
      procedures, indicating that endogeneous tRNA(met) exists stably in the MetRS
      complex. 5SRNP and 5SrRNA markedly enhanced the MetRS activity in the MetRS
      complex, indicating that 5SRNP(A) plays a role as a positive effector of MetRS.

PMID- 8982852
TI  - Gelation of the lens capsule type IV collagen solution at a neutral pH.
AB  - It is known that the type IV collagen extracted from EHS tumor assembles under a
      physiological condition, but not in a gel form. The EHS type IV collagen requires
      the other basement membrane components, laminin1, heparansulfate proteoglycan,
      and/or nidogen for gelation. On the other hand, Muraoka et al. reported that the
      bovine lens capsule type IV collagen alone gelated under a unique and unexpected
      condition of 2 M guanidine-HCl and 50 mM dithiothreitol, a condition which is
      thought to be dissociative for most biological macromolecules, including
      extracellular matrix [Muraoka, M. et al. (1996) J. Biochem. 119, 167-172]. The
      present report shows that the bovine lens capsule type IV collagen formed a gel
      under physiological conditions of pH and ionic environment, though the apparent
      rigidity of the gel was weaker than that of the gel formed in 2 M guanidine-HCl
      and dithiothreitol. The rigidity depended greatly on the incubation temperature
      and NaCl concentration of the type IV collagen solution, as observed in terms of
      the contractility of gel volume under centrifugal force. the gel formed in 150 mM
      NaCl and 20 mM phosphate, pH 7.3, at 28 degrees C contracted to 20% of the
      original volume on centrifugation of 1,800 x g for 10 min, while the gel formed
      at 4 degrees C, where type I collagen did not gelate at all, retained 90% of the
      original volume at the same centrifugal force. NaCl concentration was another
      important factor influencing the mechanical properties of type IV collagen gel.
      The gel formed at 150 mM showed maximal rigidity in the range of 0 to 300 mM in
      terms of the contractility on centrifugation. An image of a Pt/C replica of the
      gelated type IV collagen reconstituted at 4 or 28 degrees C in 20 mM phosphate,
      pH 7.3, containing 150 mM NaCl showed fine meshworks consisting of rather
      homogeneous pore sizes, resembling the skeletal structure of basal lamina. Since
      the condition where the type IV collagen alone formed gels was physiological in
      terms of ionic strength and pH, the aggregate structure and gel properties might
      reflect the in vivo type IV collagen supramolecular structure and the property.

PMID- 8982853
TI  - Effect of aluminum ion on Fe(2+)-induced lipid peroxidation in phospholipid
      liposomes under acidic conditions.
AB  - The effects of Al3+ on Fe(2+)-induced lipid peroxidation in phospholipid
      liposomes consisting of phosphatidylcholine (PC) and phosphatidylserine (PS) were
      examined under acidic conditions. The stimulatory effect of Al3+ on Fe(2+)
      induced lipid peroxidation in the liposomes showed a biphasic response against pH
      variation, and the maximum stimulation was observed around pH 6.0. In addition,
      it was found that the stimulatory effect of Al3+ on the lipid peroxidation was
      dependent on the proportion of PS in the liposomes. On the other hand, the lipid
      peroxidation in PC liposomes was not stimulated by the addition of Al3+. From
      these findings, it is suggested that the Al3+ effect on Fe(2+)-induced lipid
      peroxidation under acidic conditions is largely dependent on the phospholipid
      composition. Trivalent cations such as Tb3+ and Ga3+ also stimulated Fe(2+)
      induced lipid peroxidation in PC/PS liposomes under acidic conditions, but
      divalent cations (Zn2+ and Mn2+) showed no stimulatory effect. The extents of
      Fe2+ disappearance and Fe3+ formation during the reaction were enhanced by the
      addition of Al3+ or Ga2+, but Tb3+ had no effect on Fe2+ disappearance. The
      results with 1,6-diphenyl-1,3,5-hexatriene (DPH) showed that the fluorescence
      anisotropy of DPH-labeled PC/PS liposomes under acidic conditions was increased
      by the addition of Al3+. Furthermore, there is a relation between the extents of
      the fluorescence anisotropy of the complex and TBARS production. In contrast, the
      fluorescence anisotropy of DPH molecules embedded in PC liposomes was not changed
      by the addition of Al3+. Based on these results, a possible mechanism of the
      stimulatory effect of Al3+ on Fe(2+)-induced lipid peroxidation under acidic
      conditions is discussed.

PMID- 8982854
TI  - Isolation and identification of myosin I from porcine aorta media smooth muscle.
AB  - A complex of 110-kDa heavy chain and calmodulin was isolated from porcine aorta
      media smooth muscle and identified as myosin I. The isolated myosin I consisted
      of equimolar amounts of 110-kDa heavy chain and calmodulin. The addition of
      exogenous calmodulin to the complex revealed that a maximum of two molecules of
      calmodulin could be bound to the heavy chain. Isolated complex bound to F-actin
      in an ATP-dependent manner and its Mg(2+)-ATPase activity was activated by F
      actin. In addition, it bound to phospholipid, which is a characteristic property
      of myosin I. Calcium ions induced a structural change, which was revealed by a
      difference in the cleavage pattern and for rate of cleavage by alpha
      chymotrypsin. This behavior was similar to that reported for brush border myosin
      I [L.M. Collins and A. Bretscher (1988) J. Cell. Biol. 106, 367-373]. Calcium
      dependent structural change of a complex of 110-kDa heavy chain and calmodulin
      was found from its solubility change at various NaCl concentrations in the
      presence of ATP. A complex of 116-kDa heavy chain and calmodulin, possibly
      another type of myosin I, was also isolated. A polyclonal antibody against the
      complex of 110-kDa heavy chain and calmodulin did not recognize the 116-kDa heavy
      chain. This result suggests that at least two types of myosin Is may exist at the
      protein level in porcine aorta media smooth muscle.

PMID- 8982855
TI  - Rat liver fatty acid-binding protein: identification of a molecular species
      having a mixed disulfide with cysteine at cysteine-69 and enhanced protease
      susceptibility.
AB  - Fatty acid-binding protein (FABP) has been isolated from rat liver cytosol by two
      steps of gel-permeation chromatography on Sephadex G-75 and Sephacryl S-100 after
      ammonium sulfate precipitation. FABP fraction was eluted as two well-separated
      peaks, fractions A and B, by reversed-phase high-performance liquid
      chromatography (HPLC). The structural difference between the two fractions was
      investigated by lysyl endopeptidase digestion followed by reversed-phase HPLC of
      the digests, which identified a peptide corresponding to residues 58 through 78
      as the modified peptide. Matrix-assisted laser-desorption-ionization mass
      spectrometry and other chemical analyses of the peptides established the
      modification in fraction A as cystein-thiolation at cysteine-69. This was
      confirmed by reduction and reoxidation of the peptide and the parent molecules.
      The modification did not affect binding of fluorescent derivatives of fatty
      acids. However, the modified species was more susceptible to proteolysis by
      bovine spleen cathepsin B and cathepsin D than the unmodified species. The
      presence of a relatively large amount of cysteine (but not of glutathione) mixed
      disulfide form of FABP suggests some physiological role of this modification
      related to the redox status of the cell [Thomas, J.A., Poland, B., and Honzatko,
      R. (1995) Arch. Biochem. Biophys. 319, 1-9], and accounts, at least in part, for
      the extensive heterogeneity of liver FABP.

PMID- 8982856
TI  - Substitutions of Ser for Asn-163 and Pro for Leu-264 are important for
      stabilization of lipase from Pseudomonas aeruginosa.
AB  - The lipase gene from Pseudomonas aeruginosa was randomly mutated by error-prone
      PCR to obtain thermostable mutants, followed by screening for thermostable mutant
      lipases. Out of about 2,600 transformants, four thermostable clones were
      obtained. Their nucleotide sequences showed that they had two or three amino acid
      substitutions. Analysis of the thermal stabilization of these mutant lipases
      indicated that Asn-163 to Ser and Leu-264 to Pro mutations were essential for the
      increased stability of the lipase. We expressed a mutant lipase (StLipA-5) having
      only the Asn-163 to Ser mutation and another (StLipA-6) having only the Leu-264
      to Pro mutation in P. aeruginosa PAO1161, purified them, and then confirmed that
      the temperature which causes a 50% decrease in the activity of the non-treated
      enzyme on treatment for 30 min was increased by 1.5 and 3 degrees C,
      respectively, compared to the wild-type enzyme. However, the thermal stability of
      the mutant lipase (StLipA-7) having both mutations was increased only by 2.5
      degrees C. These mutant lipases were stabilized through a decrease in activation
      entropy. Kinetic studies showed that the Kcat/K(m) values of StLipA-5, StLipA-6,
      and StLipA-7 were decreased by 14.4, 52.9, and 26.0%, respectively.
      Interestingly, the pH-stabilities of StLipA-6 and StLipA-7 were also increased,
      especially at alkaline pH. Based on these results, the tertiary structure and
      mechanism of stabilization of the lipase were discussed.

PMID- 8982857
TI  - Muscle-type tropomyosin of sea urchin egg increases the actin-binding of
      nonmuscle-type tropomyosin.
AB  - Tropomyosin isoforms in eggs of several species of sea urchins are classified
      into two types, muscle-type and nonmuscle-type, based on their antigenicities.
      Their actin-binding abilities were investigated using muscle-type isoform (32K)
      and nonmuscle-type isoform (30K), which were purified by the method previously
      reported and separated by isoelectric focusing from eggs of sea urchin,
      Strongylocentrotus intermedius. Co-sedimentation assays revealed that 32K could
      stoichiometrically bind to actin filaments independently of the 30K, but 30K
      alone bound very poorly. The actin-binding of 30K was, however, considerably
      increased in the presence of 32K, and the molar ratio of the bound 30K and 32K
      was approximately 1:1. The increase in the actin-binding of 30K is probably
      caused by the interaction of 30K with 32K in a head-to-tail manner, as indicated
      by the higher specific viscosity of the mixture than that of 32K alone.

PMID- 8982858
TI  - Isolation and characterization of the human chromosomal gene for prostacyclin
      stimulating factor.
AB  - Prostacyclin-stimulating factor (PSF) is a protein which acts on vascular
      endothelial cells and stimulates the production of prostacyclin. Recently, we
      were able to purify PSF from the conditioned medium of cultured human diploid
      fibroblasts and clone PSF cDNA. In this study, we screened a human genomic
      library and isolated genomic clones to determine the structure of the human
      chromosomal PSF gene. By determining the nucleotide sequence and transcription
      initiation site of this gene, we found that it comprises 5 exons and 4 introns.
      Southern hybridization analysis indicated the presence of a single copy of the
      PSF gene per haploid set of chromosomes. The 300 bp upstream of the transcription
      initiation site had a very high GC content, and 7 binding sites for the
      transcription regulating factor Sp1 were present.

PMID- 8982860
TI  - The heterogeneous interaction of substoichiometric TNP-ATP and F1-ATPase from
      Escherichia coli.
AB  - The interactions of substoichiometric TNP-ATP and F1-ATPase from Escherichia coli
      (EF1) were examined and compared with those in the case of mitochondrial F1
      ATPase (MF1) and F1-ATPase from thermophilic Bacillus PS3 (TF1). EF1 hydrolyzed
      substoichiometric TNP-ATP faster than TF1 or MF1, although some 20% of the TNP
      ATP remained unhydrolyzed even in the presence of excess chase ATP. The affinity
      of the catalytic site of EF1 for the product, TNP-ADP, was weaker than that of
      TF1 or MF1, and the TNP-ADP was readily released upon addition of excess ATP. The
      amplitude of the difference absorption spectrum induced by binding of TNP-AT(D)P
      to EF1 was smaller than that of MF1 or TF1 under similar experimental conditions.
      When an excess amount of TNP-ATP was added to EF1 and the change of the
      difference spectrum was measured, the shape of the difference spectrum of the ATP
      replaceable fraction was very similar to that in the case of binding of TNP-ATP
      to the isolated beta subunit of TF1, indicating that the rapidly replaceable
      fraction of bound TNP-ATP was actually at the catalytic site and most of the non
      replaceable portion was bound at noncatalytic sites. Weaker affinity of the
      catalytic site for TNP-ATP may account for the heterogeneous binding and
      hydrolysis under the conditions described in this paper.

PMID- 8982859
TI  - Separation of the subtypes of type V collagen molecules, [alpha 1(V)]2 alpha 2(V)
      and alpha 1(V) alpha 2(V) alpha 3(V), by chain composition-dependent affinity for
      heparin: single alpha 1(V) chain shows intermediate heparin affinity between
      those of the type V collagen subtypes composed of [alpha 1(V)]2 alpha 2(V) and of
      alpha 1(V) alpha 2(V) alpha 3(V).
AB  - The heparin affinities of heat-treated type V collagen alpha-chains and the
      triple-helical molecules were evaluated in terms of the NaCl concentration
      required for prevention of binding to a heparin-Sepharose column. After heat
      treatment, alpha 1(V) chain required approximately two-fold higher NaCl
      concentration to pass through the column than the other two chains, alpha 2(V)
      and alpha 3(V). Thus, the heparin affinity of alpha 1(V) may be approximately two
      fold higher than those of the other alpha (V)-chains. The type V collagen
      molecules in triple-helical conformation were separated into two fractions at 170
      mM NaCl in 20 mM phosphate buffer, pH 7.2, containing 2 M urea; bound and non
      bound. The ratio of the three alpha-chains, alpha 1(V): alpha 2(V): alpha 3(V)
      was 2 : 1 : 0 and 1 : 1 : 1 in the bound and flow-through fractions,
      respectively, on analysis by SDS-PAGE. The differential affinity of the two
      fractions could be accounted for by the number of alpha 1(V) chains in the triple
      helical molecule, if these fractions contained triple-helical subtypes with the
      chain compositions of [alpha 1(V)]2 alpha 2(V) and alpha 1(V) alpha 2(V) alpha
      3(V), respectively. From the comparison of the NaCl concentration required for
      prevention of the binding, [alpha 1(V)]2, alpha 2(V) had about two-fold higher
      affinity than alpha 1(V) alpha 2(V) alpha 3(V), and the separated alpha 1(V)
      chain showed an intermediate affinity. A possible explanation for difference in
      heparin affinity among the subtypes of molecules and the separated alpha-chains
      is that the heparin affinity of type V collagen molecule is governed by the
      number of alpha 1(V) chains contained in the molecule and that steric restraint
      in a triple-helical conformation weakens the binding of alpha 1(V) chain to
      heparin.

PMID- 8982861
TI  - Acid and thermal unfolding of Escherichia coli dihydrofolate reductase.
AB  - The acid and thermal unfolding of Escherichia coli dihydrofolate reductase (DHFR)
      were studied by means of circular dichroism (CD) and fluorescence spectroscopy.
      There existed at least one intermediate around pH 4 in the acid unfolding process
      at 15 degrees C, in which the tertiary structure was disrupted before unfolding
      of the secondary structure. The fluorescence energy transfer from intrinsic
      tryptophan residues to 1-anilinonaphthalene-8-sulfonate suggested the disruption
      of the tertiary structure around some tryptophan residues of the intermediate.
      The thermal unfolding process at pH 7.0 also involved at least one intermediate
      having a disrupted tertiary structure and a folded secondary structure. The three
      state thermodynamic analysis showed that the intermediate in thermal unfolding
      was less stable by 1.8 kcal/mol than the native state. The similarity of the far
      ultraviolet CD spectra of acid and thermally unfolded forms suggests that both
      types of unfolding produce the same structure, which may be a molten globule
      intermediate such as that in the folding kinetics of DHFR. The acid and thermal
      unfolding were depressed in the presence of KCl due to stabilization of the
      native form.

PMID- 8982863
TI  - Molecular cloning of the Xenopus c-met/hepatocyte growth factor receptor and its
      regional expression during early development.
AB  - Hepatocyte growth factor (HGF), a ligand for c-Met receptor tyrosine kinase,
      regulates the cell growth, migration and morphogenesis of a wide variety of
      cells, and plays important roles in organogenesis in embryos as well as
      regeneration of organs. HGF is structurally conserved in Xenopus laevis, and the
      Xenopus HGF gene is expressed in neurula and tailbud embryos. In the present
      work, we cloned complementary DNA for the Xenopus Met/ HGF receptor and analyzed
      its expression during embryogenesis. The open reading frame of Xenopus c-met is
      4,125 base pairs long and encodes a putative polypeptide of 1,375 amino acids.
      The deduced amino acid sequences of the Xenopus and human Met proteins are 63%
      identical, the tyrosine kinase domains in the intracellular regions showing
      particular homology, over 90% identity in the amino acid sequences between
      Xenopus and human. During Xenopus embryogenesis, c-met mRNA was expressed at a
      high level from the gastrula to the neurula stage, while HGF mRNA expression was
      seen from the early neurula stage. Whole mount in situ hybridization showed that
      c-met mRNA was specifically localized in the foregut region, mesenchymal tissue
      of the tailbud, and neural tissues in neurula embryos. Thus, c-Met is a highly
      conserved molecule in a wide range of species, as is its ligand, HGF. The HGF-Met
      system may be involved in early multiple organogenesis in Xenopus embryos.

PMID- 8982862
TI  - Porcine vitronectin, the most compact form of single-chain vitronectin: the
      smallest molecular mass among vitronectins was ascribed to deletion and
      substitution of base pairs, and proteolytic trimming of the peptide.
AB  - Vitronectin is a multifunctional glycoprotein regulating the fibrinolysis,
      complement, and coagulation systems in plasma, besides exhibiting cell-spreading
      activity. Porcine vitronectin has an unusually small molecular mass among the
      vitronectins hitherto found, which seems to make it hard for it to retain all the
      known activities. In this study, the complete primary structure of porcine
      vitronectin was elucidated by cloned cDNA and glycoprotein analyses. A coding
      sequence of 459 amino acids including a signal peptide of 19 amino acids was
      deduced from the cDNA. The coding sequence showed 70.3% homology with that of
      human vitronectin, but porcine vitronectin lacked 22 amino acids in the
      connecting region. One amino acid substitution resulted in the loss of a
      potential glycosylation site in accordance with the finding on glycopeptide
      analyses that porcine vitronectin contained two kinds of glycosylated sequences,
      while human vitronectin contained three. C-Terminal analysis of porcine
      vitronectin indicated that an 80 amino acid fragment was completely removed from
      the C-terminal end on proteolytic processing. Thus, porcine vitronectin only
      exists in a truncated single-chain form representing the most compact functional
      form of vitronectin, which suggests the lack of functional necessity of the
      truncated C-terminal fragment.

PMID- 8982864
TI  - Cloning, sequence analysis, and expression in Escherichia coli of the gene
      encoding the Candida utilis urate oxidase (uricase).
AB  - A urate oxidase (uricase) gene was cloned from Candida utilis with an
      oligonucleotide probe based on the amino acid sequence of cyanogen bromide
      cleaved uricase. The uricase gene contains 909 base pairs and encodes a protein
      with a predicted mass of 34,193 Da. Candida uricase was similar (49% match in
      amino acid sequence) to the uricase from Aspergillus flavus. The uricase from
      Candida utilis has four cysteines and one of them, Cys168, participates in the
      enzyme activity. This enzyme was expressed to a level of about 20% of total
      cellular protein in an Escherichia coli cell as a soluble and functional form.

PMID- 8982865
TI  - Characterization of the S1 subsite specificity of aspergillopepsin I by site
      directed mutagenesis.
AB  - The structural determinants of S1 substrate specificity of aspergillopepsin I
      (API; EC 3.4.23.18), an aspartic proteinase from Aspergillus saitoi, were
      investigated by site-directed mutagenesis. Aspartic proteinases generally favor
      hydrophobic amino acids at P1 and P1'. However, API accommodates a Lys residue at
      P1, which leads to activation of trypsinogen. On the basis of amino acid sequence
      alignments of aspartic proteinases, Asp-76 and Ser-78 of API are conserved only
      in fungal enzymes with the ability to activate trypsinogen, and are located in
      the active-site flap. Site-directed mutants (D76N, D76E, D76S, D76T, S78A, and
      delta S78) were constructed, overexpressed in Escherichia coli cells and purified
      for comparative studies using natural and synthetic substrates. Substitution of
      Asp-76 to Ser or Thr and deletion of Ser-78, corresponding to the mammalian
      aspartic proteinases, caused drastic decreases in the activities towards
      substrates containing a basic amino acid residue at P1. In contrast, substrates
      with a hydrophobic residue at P1 were effectively hydrolyzed by each mutant
      enzyme. These results demonstrate that Asp-76 and Ser-78 residues on the active
      site flap play important roles in the recognition of a basic amino acid residue
      at the P1 position.

PMID- 8982866
TI  - Lanosterol 14-demethylase activity expressed in rat brain microsomes.
AB  - The occurrence of sterol 14-demethylase in rat brain microsomes was confirmed.
      The brain microsomes from adult rats converted lanosterol into its 14
      demethylated products, 4,4-dimethylcholesta-8, 24-dienol, and 4,4
      dimethylcholesta-8,14,24-trienol, in the presence of NADPH and molecular oxygen.
      This metabolism of lanosterol was inhibited by carbon monoxide and ketoconazole,
      a potent inhibitor of sterol 14-demethylase P450 (P45014DM or CYP51). These facts
      indicated the occurrence of lanosterol 14-demethylation in rat brain microsomes
      and its dependency on P45014DM. A representative value of the lanosterol
      demethylase activity of the brain microsomes was 8.4 pmol/min/mg protein or 640
      pmol/ min/nmol of total P450. The former was about one-thirteenth of the
      corresponding value observed with liver microsomes from the same rats, while the
      latter was 4-times higher than the corresponding value obtained with the liver
      microsomes. This fact suggested that the ratio of P45014DM to other P450 species
      was higher in brain than in liver. Lanosterol 14-demethylation is situated at the
      root of the sterol-biosynthetic branch of the mevalonic acid pathway. Therefore,
      the present finding enzymologically supports the existence of the sterol
      biosynthetic pathway in brain.

PMID- 8982867
TI  - Genomic structures and characterization of Rae1 family members encoding GPI
      anchored cell surface proteins and expressed predominantly in embryonic mouse
      brain.
AB  - Rae1 alpha, Rae1 beta, and Rae1 gamma cDNAs isolated from retinoic acid-treated
      mouse embryonal carcinoma F9 cells encode cell surface proteins sharing partial
      homology with MHC class I molecules, and mRNAs corresponding to these cDNAs were
      detected exclusively in early mouse embryos, especially in the head region. To
      initiate studies on their roles, the rae1 alpha gene and the genomic DNAs
      covering the complete coding regions of the rae1 beta and rae1 gamma genes were
      isolated and their structures were analyzed. Although the coding regions of the
      three rae1 genes were highly homologous, the restriction map of the 5'-end region
      of the rae1 alpha gene differed from that of the rae1 beta and rae1 gamma genes.
      The rae1 family members were mapped by FISH on mouse chromosome 10A4 region.
      Genomic DNAs hybridizable with a Rae1 cDNA were not detected in rat and human.
      Rae1 genes were preferentially expressed in early mouse embryos, preferentially
      in the brain, and RAE1 proteins were anchored on the cell surface by a glycosyl
      phosphatidylinositol (GPI)-tail, a feature shared by important cell surface
      ligands.

PMID- 8982868
TI  - Importance of N-terminal regions of G protein alpha subunits for the activation
      of phospholipase C in Xenopus oocytes.
AB  - The alpha subunits of Gq family G proteins, GL1 alpha and GL2 alpha, are bovine
      homologues of mouse G14 alpha and G11 alpha, respectively, and are closely
      related to each other. When expressed in Xenopus oocytes together with
      metabotropic glutamate receptors, GL2 alpha activates endogenous phospholipase C
      (PLCx) in response to glutamate stimulation, whereas GL1 alpha inhibits the
      activation of PLCx. By examining the properties of 10 chimeras between GL1 alpha
      and GL2 alpha and their mutants, we tried to identify the regions on the G alpha
      proteins that are important for the activation of PLCx. The results indicated
      that a necessary (but not sufficient) condition for a chimeric G alpha protein to
      be able to clearly activate PLCx was that its N-terminal quarter portion should
      be derived from GL2 alpha. No correlation was found between the origin (GL1 alpha
      or GL2 alpha) of C-terminal regions of the chimeras and the ability of chimeras
      to activate PLCx. One of the chimeras is different from GL2 alpha at only four
      amino acid residues in the N-terminal region, and yet it could not activate PLCx.
      When one of the four residues, Ser-59, in the chimera was mutated back to Ala as
      in the original GL2 alpha, the resulting mutant became capable of activating
      PLCx. This residue is localized in the midst of the N-terminal linker connecting
      the two major domains in the G alpha proteins. These results indicate that Ala-59
      is critical for the activation of PLCx, and that the linker may play important
      roles in determining functions of G alpha proteins.

PMID- 8982869
TI  - Detection of UDP-D-xylose: alpha-D-xyloside alpha 1-->3xylosyltransferase
      activity in human hepatoma cell line HepG2.
AB  - We previously reported the detection of novel O-linked sugar chains classified as
      being of the glucosyl-O-serine type [Hase et al. (1988) J. Biochem. 104, 867
      868]. The sugar chains are a disaccharide (Xyl alpha 1-3Glc) and a trisaccharide
      (Xyl alpha 1-3Xyl alpha 1-3 Glc) linked to serine residues in epidermal growth
      factor-like domains of human and bovine blood coagulation factors. The structures
      of these sugar chains suggested the presence of an alpha 1-->3xylosyltransferase
      for their biosynthesis. We report here on the detection of alpha 1-
      >3xylosyltransferase activity which catalyzes the transfer of xylose to Xyl alpha
      1-3Glc in the human hepatoma cell line HepG2. We employed pyridylaminated Xyl
      alpha 1-3Glc as a fluorescent acceptor and UDP-D-Xyl as a donor. The reaction
      product was purified by reversed-phase HPLC, and the structure of the transfer
      product isolated was confirmed to be pyridylaminated Xyl alpha 1-3Xyl alpha 1
      3Glc by Smith degradation, mass spectrometry, and alpha- and beta-xylosidase
      digestions. The apparent K(m) value for pyridylaminated Xyl alpha 1-3Glc was 52
      mM and for UDP-D-Xyl 0.28 mM. Optimum pH was 7.2. The enzyme was inactivated by
      addition of EDTA, and its activity was restored by addition of Mn2+ and Mg2+.
      These results indicate the presence of a novel enzyme which is able to transfer
      xylose to Xyl alpha 1-3Glc, forming Xyl alpha 1-3Xyl alpha 1-3Glc in human cells.

PMID- 8982870
TI  - Galectin-1 from bovine spleen: biochemical characterization, carbohydrate
      specificity and tissue-specific isoform profiles.
AB  - Selected biochemical properties, including the charge heterodispersity profile
      and carbohydrate specificity, of bovine galectin-1 were determined in detail. The
      lectin was purified through an improved purification protocol that yielded 35-40
      mg/kg of wet tissue with a specific activity of 1.7-2 x 10(4) mg-1.ml. The
      galectin is a homodimer of approximately 14.5 kDa subunits with E(280)mg/ml of
      0.65 ml.mg-1.cm-1. When stored in the presence of its carbohydrate ligand, the
      lectin's binding activity remained stable in a non-reducing environment even at
      room temperature. The optimal pH for binding to the ligand was 6.5-8.0. The
      overall carbohydrate specificity of the bovine galectin-1 isolated from spleen is
      similar to that of the galectin isolated from heart and to other mammalian
      galectins that exhibit "conserved" (Type I) carbohydrate recognition domains
      (CRDs) [Ahmed, H. and Vasta, G.R. (1994) Glycobiology 4, 545-549], but differs
      from those from Xenopus laevis and rat intestine domain I. The fluorescence of 4
      methylumbelliferyl alpha-D-galactopyranoside was quenched on binding to bovine
      spleen galectin-1. Scatchard plots of data obtained at 5, 15, and 30 degrees C
      showed that the galectin has two sugar exothermic binding sites with association
      constants of 3.4 x 10(5), 1.0 x 10(5), and 0.3 x 10(5), respectively. Chemical
      modification studies indicated that histidine, tryptophan, carboxylic acid, and
      arginine, but not lysine or tyrosine, are involved in the binding to the
      carbohydrate ligand. On isoelectric focusing, the spleen galectin-1 appeared as
      six isoforms ranging from pI4.56-4.88 with main components at pI 4.63 (34.0%),
      4.73 (42.6%), and 4.88 (16.6%). The galectin-1 isolated from heart yielded a
      quali- and quantitatively different profile with four isoforms ranging from pI
      4.53-4.73, those with pIs of 4.56, 4.63, and 4.73 being common to the spleen
      homolog. Edman degradation of selected peptides purified from the spleen galectin
      1 digest revealed amino acid sequences identical to those obtained for the heart
      galectin-1. This suggests that although point mutations in the subunit primary
      structure may not be the likely source of isolectins, as observed for X. laevis,
      tissue-specific co- or post-translational modifications may be the possible cause
      of the differences in the galectin isoform profile between bovine spleen and
      heart.

PMID- 8982871
TI  - The molecular cloning and expression of alpha 2,8-sialyltransferase (GD3
      synthase) in a rat brain.
AB  - We have cloned the cDNA for a GD3 synthase (alpha-2,8-sialyltransferase, [EC
      2.4.99.8]) from a rat embryonic brain cDNA library. Mammalian cells transfected
      with the cloned cDNA expressed GD3 on the cell surface and showed GD3 synthase
      activity. The deduced protein (342 amino acid residues) was predicted to have a
      type II membrane topology containing the "sialyl motif" and was found to be 91%
      similar to its human homologue. Analysis of the acceptor specificity of GD3
      synthase protein indicated that this enzyme catalyzed the biosynthesis of GT1a
      and GQ1b as well as GD3. Northern blot analyses showed that the GD3 synthase gene
      is preferentially transcribed in the brain and the spleen. The expression of GD3
      synthase mRNA was developmentally regulated, with the highest level in the brain
      during embryonic days 15 to 18. In situ hybridization analyses demonstrated that
      the GD3 synthase is strongly expressed in the ventricular/subventricular zone of
      the embryonic rat brain and retina. In the adult rat, GD3 synthase mRNA was
      detected in the cerebral cortex, hippocampus, thalamus, and cerebellum. These
      studies show that the spatio- and stage-restricted expression of GD3 in the
      developing rat brain may be regulated in part by the level of GD3 synthase mRNA.

PMID- 8982872
TI  - Protein-RNA and protein-protein interactions of the Drosophila sex-lethal
      mediated by its RNA-binding domains.
AB  - The Drosophila Sex-lethal (Sxl) contains two RNA-binding domains (RBDs) which
      belong to the RNA recognition motif (RRM) group. Sxl binds to a specific uridine
      rich sequence which is believed to be the major cis-acting element for the
      splicing regulation of the transformer (tra) mRNA precursor. Here we show
      evidence supporting the previous suggestion that Sxl recognizes the sequence
      context downstream of the uridine-rich sequence. In addition, by means of UV
      crosslinking assays with Sxl deletion constructs, we have demonstrated that Sxl
      RNA binding requires both of its RBDs for specificity and strength. Moreover, by
      the yeast two-hybrid analysis, we found that homodimeric interaction occurs
      between two Sxl molecules. Interestingly, the amino- and carboxy-terminal regions
      outside of the Sxl RBDs are dispensable for such dimerization, indicating that
      the protein-protein interaction is also mediated by RBDs. Coprecipitation
      experiments in vitro showed that the protein-protein interaction seems to be RNA
      dependent but greatly enhanced by addition of the specific RNA containing the Sxl
      binding site, suggesting that the conformational change which is induced on
      binding to RNA may facilitate the interaction between Sxl molecules.

PMID- 8982873
TI  - Expression of cadherin-catenin complexes in human leukemia cell lines.
AB  - Cadherins are Ca2(+)-dependent cell-cell adhesion molecules, and are involved in
      the formation and maintenance of the histo-architecture. Using cultured human
      leukemia cell lines (adult T cell leukemia and thymus-derived lymphoma cell
      lines), we obtained evidence that cadherins and catenins are expressed in these
      cell lines but not in normal leukocytes. Immunoblot analysis of cells using a pan
      cadherin serum, directed against the conserved carboxyl-terminus of cadherins,
      revealed a major band of 130 kDa and a minor one of 135 kDa. The 130 kDa cadherin
      was also recognized by anti-N-cadherin antibodies. A human N-cadherin cDNA probe
      hybridized to a 4.3 kb mRNA isolated from cells immunologically positive for N
      cadherin. Sequencing of the cDNA fragments isolated from the cells revealed a N
      cadherin sequence. Cell surface expression of N-cadherin was confirmed by
      indirect immunofluorescence staining of the cells. Immunoblot and Northern blot
      analyses also revealed the presence of alpha-catenin, beta-catenin, and gamma
      catenin (plakoglobin) in these cell lines. Immunoprecipitation with anti-N
      cadherin antibodies and subsequent immunoblot analysis with anti-catenin
      antibodies revealed that N-cadherin is associated with alpha- and beta-catenins,
      a prerequisite for cadherins to be functional. These results suggest an important
      role of the cadherin-catenin complexes in the behavior of the leukemia cells.

PMID- 8982874
TI  - Isolation and characterization of ECT1 gene encoding CTP: phosphoethanolamine
      cytidylyltransferase of Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae mutants that were unable to utilize extracellular
      ethanolamine for phosphatidylethanolamine synthesis were isolated. Two of them
      carried recessive chromosomal mutations in a same gene and were defective in
      CTP:phosphoethanolamine cytidylyltransferase (ECT) activity in vitro (Ect-). In
      an Ect- mutant that also carried the cho1 mutation, phosphatidylethanolamine
      accounted for less than 2% of total phospholipids, suggesting the importance of
      ECT in phosphatidylethanolamine synthesis. By screening a genomic library on a
      low copy number vector, three complementary clones of different size were
      isolated. A 2.8-kb common DNA region carried an open reading frame (ORF) of 969
      bp in length, of which a truncated from failed to complement the Ect- mutation.
      This ORF was identical to the previously isolated MUQ1 gene of unknown function.
      Its deduced amino acid sequence had significant similarity to CTP: phosphocholine
      cytidylyl-transferases of yeast and rat. The entire ORF, when combined with the
      glutathione S-transferase gene and expressed in Escherichia coli, exhibited ECT
      activity. These results indicate that the cloned gene encodes a catalytic subunit
      of ECT of S. cerevisiae.

PMID- 8982876
TI  - The meaning of the acronym MULTIFIT.

PMID- 8982875
TI  - Differential tissue-specific expression of neurofibromin isoform mRNAs in rat.
AB  - We have cloned the full-length cDNA encoding the rat homolog of type I
      neurofibromin isoform, a protein product of a gene linked to neurofibromatosis
      type 1. Rat type I neurofibromin isoform is composed of 2,820 amino acid residues
      and shares about 98.5% amino acid identity with the human counterpart. By S1
      nuclease mapping analysis of the alternatively spliced neurofibromin mRNAs in
      adult rat tissues, we showed that type I isoform mRNA was predominantly expressed
      in the brain, pituitary, and testis, while type II mRNA, carrying a 63-nucleotide
      insertion in the region coding for the domain related to GTPase-activating
      protein, was predominantly expressed in most other tissues, such as heart,
      kidney, and ovary. Furthermore, type II mRNA is predominant in the testis at age
      1 week, while type I mRNA becomes predominant at 3 weeks and is subsequently
      expressed at higher levels, as seen in the adult testis. In contrast, type I mRNA
      is the predominant form in the brain throughout the postnatal development. Thus,
      the relative expression levels of type I and type II mRNAs may be specific to the
      tissues and to the developmental stage of certain tissues.

PMID- 8982877
TI  - Clinical pathway across tertiary and community care after an interventional
      cardiology procedure.
AB  - Many patients who receive medical interventional cardiology procedures at a
      tertiary hospital live outside the metropolitan area and may experience
      fragmentation in care, less emotional support by family members, inaccurate and
      delayed communication, and lack of educational follow-up on discharge from the
      hospital. A clinical pathway titled "Heart Health Care Patterns" was developed to
      link acute phase, recovery phase, rehabilitation phase, and
      enhancement/maintenance phase. The 12-month clinical pathway combines Gordon's
      Functional Health Patterns and the Omaha System developed by the Omaha Visiting
      Nurse Association. The rating scale for outcomes assesses the patient at
      different phases to provide objective data and information throughout the year.

PMID- 8982878
TI  - Study of mechanical versus manual/mechanical compression following various
      interventional cardiology procedures.
AB  - Knowledge and technology for cardiovascular disease are growing at a rapid rate.
      Interventional cardiology offers patients several options of therapy, including
      percutaneous transluminal coronary angioplasty, directional coronary atherectomy,
      and percutaneous transluminal coronary rotoblator angioplasty procedures.
      Patients with these procedures require femoral intra-arterial sheath insertion
      and postprocedure management of these sheaths. The best practice for sheath
      removal is a controversial issue. This article describes a study conducted at
      Presbyterian Hospital in Charlotte, North Carolina, comparing the use of
      manual/mechanical versus mechanical compression technique for sheath removal.
      Subjects included patients who had one of the previous procedures performed.
      Subjects were randomly assigned to one of two study groups: manual/ mechanical or
      mechanical compression. Variables such as size of sheath, anticoagulants,
      antiplatelets, and flat time after sheath removal were examined. The outcome
      measure reported was the development of a groin complication. Results indicated
      no significant difference in groin complication. As a result, practice at
      Presbyterian Hospital changed to mechanical compression for removing sheaths.

PMID- 8982879
TI  - Reducing costs and improving processes for the interventional cardiology patient.
AB  - The cardiology unit at the University of Chicago Hospitals developed a cost
      saving mechanism in the care of postinterventional cardiology patients, reducing
      time spent in the coronary care unit. Increased nursing education and training
      and better identification of patient outcomes made this collaborative effort a
      cost-saving and effective pilot.

PMID- 8982880
TI  - Strategies for effective patient education material design.
AB  - In the current health care system, written patient education tools are important.
      Well-written and easy-to-understand materials are essential to assist the patient
      in recovery and increasing compliance. The purpose of patient education is to
      provide the patient with the knowledge needed for self-care. This article
      discusses strategies to design effective written patient education material.

PMID- 8982881
TI  - Developing a cardiac catheterization education program.
AB  - This article describes the establishment of a coordinated education program for
      patients having a cardiac catheterization. The article focuses on developing the
      program content, instructional aids, and the education of the staff doing the
      actual patient education for this group of patients and their families.

PMID- 8982882
TI  - Driving with an internal defibrillator: legal, ethical, and quality-of-life
      issues.
AB  - Patients with internal cardioverter-defibrillators experience many issues after
      implantation. One issue is operating a motor vehicle. This issue has many
      ethical, legal and quality-of-life concerns that must be addressed by the
      patient, health care providers, and society. The legal and ethical issues
      surrounding patients with internal cardioverter-defibrillators will be explored
      using an ethically based theoretical framework.

PMID- 8982883
TI  - The ABCs of teaching advanced cardiac life support.
AB  - This article describes the evolution in methods used at The Christ Hospital in
      Cincinnati, Ohio, to teach advanced cardiac life support over the past 10 years.
      The interactive nature of the teaching methods has improved participants'
      enjoyment of this course. With smaller teaching groups, instructors find this
      course challenging and fun to teach. This article provides outlines of teaching
      stations at The Christ Hospital and examples in which to implement the current
      advanced cardiac life support content according to the American Heart
      Association's teaching recommendations.

PMID- 8982884
TI  - The darkness shall be the light.
AB  - This case study is the author's attempt to share a cardiac patient's experience
      in a personal and respectful manner. Case studies ordinarily share all of the
      medical and physiologic aspects of what is happening to patients and leave out
      the essence of the person. This is an effort to go beyond the ordinary and see
      the human being who has had a severe myocardial infarction and now lies in an
      intensive care unit. The nature of one patient's struggle through darkness may be
      realized with the use of the patient's own words, information from family
      members, and the creative expressions of the author.

PMID- 8982885
TI  - An update to the medical device reporting requirements of the Safe Medical Device
      Act.
AB  - The Safe Medical Devices Act made hospitals, nursing homes, and a variety of
      other health care organizations responsible for identifying and reporting
      injuries associated with the use of medical devices. The Final Regulation for the
      Medical Device Reporting of adverse events became effective on July 31, 1996. The
      Final Regulations incorporate significant changes from the "Proposed Final
      Regulations," and these changes need to be conveyed to appropriate staff of all
      device user facilities. Changes include the mandated reporting of user error, the
      Food and Drug Administration emphasis on the device manufacturer as the prime
      investigator of adverse events, the 10-day reporting rule that now becomes
      effective as soon as the facility becomes aware of the event, and the
      clarification of definitions for user facilities. Staff education and training
      are no longer mandated by the regulations, but some education is required if
      compliance with the law is to be ensured.

PMID- 8982886
TI  - Case study: analysis of dual chamber rate responsive pacing in atrial
      fibrillation.
AB  - This article presents a case study of a patient who required a dual chamber rate
      responsive pacemaker to assist in managing atrial fibrillation. The patient
      developed significant bradycardia when treated with the dose of propafenone
      required to convert atrial fibrillation, so the pacemaker was inserted. An
      example of a paced rhythm is presented and a differential diagnosis approach is
      used to discuss the possible interpretations of the rhythm. A brief explanation
      of the actual cause of the observed paced rhythm is presented.

PMID- 8982888
TI  - Incidence of perioperative myocardial ischemia in TURP patients.
AB  - STUDY OBJECTIVE: To determine the incidence of new episodes of myocardial
      ischemia in patients undergoing transurethral resection of the prostate (TURP).
      DESIGN: Prospective, nonrandomized study. SETTING: Veterans Administration
      medical center. PATIENTS: 39 patients undergoing elective TURP. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Myocardial ischemia was detected with a 3
      channel ambulatory ECG recorded. The ambulatory ECG recorder was applied
      preoperatively and removed when the patient left the recovery room. New
      myocardial ischemia was defined as a 1 mm or greater ST depression or a 2 mm or
      greater ST elevation from baseline, lasting for 1 minute or longer in at least
      one lead at the J point plus 60 msec unless this point fell within the T wave, in
      which case the J point 40 msec or greater was used. ST changes consistent with
      myocardial ischemia were confirmed by a cardiologist blinded to the patient's
      clinical course. Seven of 39 TURP patients (18%) had ST segment changes
      indicative of new myocardial ischemia. These seven patients had more prostate
      tissue resected and more blood loss than the 32 patients who did not have any
      myocardial ischemia (p < 0.05). CONCLUSIONS: Patients undergoing TURP have an 18%
      incidence of myocardial ischemia. Patients undergoing TURP with more prostate
      tissue resected and greater blood loss are at increased risk for perioperative
      myocardial ischemia.

PMID- 8982887
TI  - Propofol and alfentanil for sedation during placement of retrobulbar block for
      cataract surgery.
AB  - STUDY OBJECTIVE: To determine if the addition of alfentanil to propofol is more
      effective than propofol alone to provide adequate conditions for placement of a
      retrobulbar block prior to cataract surgery. DESIGN: Randomized, double-blinded
      study. SETTING: Outpatients at a university hospital. PATIENTS: 40 adult ASA
      physical status I, II, and III outpatients scheduled for elective cataract
      surgery. INTERVENTIONS: Patients were randomly assigned to receive one of four
      drug combinations prior to the placement of a retrobulbar block: Group 1,
      propofol alone; Group 2, alfentanil 5 micrograms/kg plus propofol; Group 3,
      alfentanil 10 micrograms/kg plus propofol; Group 4, alfentanil 15 micrograms/kg
      plus propofol. All patients were preoxygenated by face mask for two minutes prior
      to drug administration. The quality of conditions for block placement were
      determined by: (1) assessing the amount of movement by the patients while the
      block needle was in place, (2) cooperativeness of the patients during the
      operation, (3) hemodynamic side effects, (4) incidence and severity of
      respiratory depression, (5) incidence of nausea and vomiting, (6) recall of
      placement of the block, and (7) time to discharge from the hospital. MEASUREMENTS
      AND MAIN RESULTS: The addition of alfentanil to propofol for sedation prior to
      placement of the retrobulbar block resulted in a dose-dependent reduction in
      movement by the patients. However, the highest dose of alfentanil (15
      micrograms/kg) resulted in the greatest frequency (40% of the patients in this
      group) of respiratory depression (SpO2 < 90%). All patients were cooperative
      during the operation and responsive to verbal command within 5 minutes of
      placement of the block. In addition, all of the patients denied being nauseated,
      having vomited, or recalling block placement in the recovery room or the next
      day. CONCLUSIONS: The combination of alfentanil and propofol may be used to
      sedate patients in order to limit movement and provide a cooperative, alert
      patient with stable hemodynamics and limited respiratory depression during
      placement of retrobulbar block prior to ophthalmic surgery. However, excessive
      dosage of these drugs may result in hazardous respiratory depression in this
      patient population.

PMID- 8982889
TI  - No change in ST segment during instillation of eyedrops of ophthalmic surgery: a
      study in elderly patients with heart disease (is present software/technology
      sufficiently sensitive)?
AB  - STUDY OBJECTIVE: To study the safety of instillation of eyedrops prior to
      ophthalmic surgery, which may potentially affect myocardial function, using
      continuous ST segment recording. DESIGN: Prospective study. SETTING: Ambulatory
      surgery preoperative area at a university hospital. PATIENTS: 30 nonpremedicated
      ASA status III adults (aged 73 to 92 years) scheduled for cataract surgery with
      monitored anesthesia care (MAC). INTERVENTIONS: All patients were given
      ophthalmic drugs consisting of phenylephrine 2.5%, flubiprofen 0.03%, mydriacyl
      1%, and cyclopentolate 1%. MEASUREMENTS AND MAIN RESULTS: ST segments were
      continuously monitored after the instillation of the eyedrops for a period of up
      to 15 minutes. A change of 2 mm or more in ST segments from baseline was
      considered significant. Results showed no significant change in ST segment. No
      patient reported any new cardiac symptoms or showed any evidence of dysrhythmias
      or hemodynamic changes. CONCLUSIONS: The lack of significant finding most likely
      reflects the safety of these ophthalmic drops in their present dilute
      concentration, but it is also possible that the software and/or monitors used
      were not sensitive enough in their current configuration to detect possible
      subtle changes. Based on the results of this study, we conclude that the
      preoperative ophthalmic drugs used in our institution do not seem to have any
      adverse cardiovascular effects in this elderly patient population who are about
      to undergo cataract surgery with MAC.

PMID- 8982890
TI  - Postoperative analgesia and intraoperative inhalational anesthetic requirements
      during umbilical herniorrhaphy in children: postincisional local infiltration
      versus preincisional caudal epidural block.
AB  - STUDY OBJECTIVE: To determine the postoperative analgesic efficacy of, and the
      effects on, intraoperative inhalational anesthetic requirements of preincisional
      caudal epidural block versus postincisional infiltration of local anesthetic
      following umbilical herniorrhaphy in children. DESIGN: Randomized, double-blind,
      prospective study. SETTING: University medical center. PATIENTS: 16 ASA status I
      and II patients (11 males, 5 females), ages 11 to 20 months, weighing up to 17
      kg. INTERVENTIONS: During standard anesthetic care, 16 children were randomized
      to receive either caudal block with 1.5 ml/kg of 0.2% bupivacaine (group I) or
      local infiltration of the surgical site with up to 1.2 ml/kg of 0.25% bupivacaine
      (Group 2). MEASUREMENTS AND MAIN RESULTS: Patients in Group I had significantly
      decreased pain scores and requirements for supplemental postoperative intravenous
      (IV) fentanyl. Five of eight patients in Group 1 did not require supplemental IV
      fentanyl during their in-hospital postoperative course, while all eight patients
      in Group 2 required supplemental IV fentanyl. The patients who received caudal
      epidural block also had decreased intraoperative requirements for isoflurane,
      shorter time to extubation (4.1 +/- 0.8 min vs. 8.4 +/- 1.5 min), and quicker
      discharge home (129 +/- 13 min vs. 163 +/- 22 min). Five of eight patients in
      Group 1 were ready for discharge at our usual time of 120 minutes, as opposed to
      one of eight patients in Group 2. CONCLUSION: Preincisional caudal epidural block
      is more effective in controlling pain following umbilical herniorrhaphy than is
      postincisional local infiltration.

PMID- 8982891
TI  - A comparison: the efficacy of sevoflurane-nitrous oxide or propofol-nitrous oxide
      for the induction and maintenance of general anesthesia.
AB  - STUDY OBJECTIVE: To compare sevoflurane-nitrous oxide with propofol-nitrous oxide
      for the induction and maintenance of anesthesia, and to determine the rates of
      recovery following each anesthetic. DESIGN: Randomized, controlled study.
      SETTING: Teaching hospital. PATIENTS: 50 ASA physical status I and II patients,
      ranging in age from 18 to 70 years. INTERVENTIONS: General anesthesia was induced
      with either sevoflurane or propofol and maintained with 60% to 70% nitrous oxide
      and either sevoflurane or a propofol infusion and supplemental fentanyl. At the
      conclusion of surgery, the oxygen flow was increased to 6 L/min and all
      anesthetics were discontinued simultaneously. Patients were monitored for the
      nature and speed of induction and emergency from anesthesia. MEASUREMENTS AND
      MAIN RESULTS: Induction of anesthesia was significantly slower in the sevoflurane
      group than in the propofol group (2.0 +/- 1.1 vs. 0.8 +/- 0.5 min, respectively).
      The ease of induction and the time required for emergence from anesthesia were
      the same in both study groups (eye opening: 9.0 +/- 4.4 min vs. 8.0 +/- 5.0 min;
      following commands: 11.2 +/- 5.0 min vs. 9.8 +/- 6.9 min; extubation: 9.1 +/- 4.5
      min vs. 8.6 vs. 5.1 min in the sevoflurane and propofol groups, respectively).
      Patients in the sevoflurane group experienced nausea and vomiting more frequently
      than patients in the propofol group (13 and 5 patients vs. 3 and 0 patients in
      the sevoflurane and propofol groups, respectively), which were not related to the
      administration of neostigmine or intraoperative opioids. CONCLUSION: Sevoflurane
      allows for rapid inhalation induction of, and emergence from, general anesthesia.

PMID- 8982892
TI  - Ondansetron prevents postoperative emesis in male outpatients. S3A-379 Study
      Group.
AB  - STUDY OBJECTIVES: To determine (1) the efficacy and safety of ondansetron in the
      prevention of postoperative nausea and vomiting (PONV) in male outpatients; (2)
      prognostic factors for PONV in male outpatients; and (3) patients' perceptions of
      the debilitating effects of PONV in the ambulatory surgery setting. DESIGN:
      Prospective, randomized, stratified, double-blind study. SETTING: Multicenter-24
      medical centers. PATIENTS: 468 ASA physical status I and II males at least 12
      years of age scheduled for general anesthesia. INTERVENTIONS: All patients
      received intravenous ondansetron 4 mg or placebo prior to undergoing general
      balanced (opioid) anesthesia. MEASUREMENTS AND MAIN RESULTS: In the
      postanesthesia care unit (PACU), the number of emetic episodes, vital signs,
      adverse events, and nausea assessments were recorded by a blinded observer. After
      discharge, and until the end of the 24-hour study period, patients completed a
      diary that collected emetic episodes, adverse events, nausea, and
      pharmacoeconomic data. There were no differences in patient demographics or
      safety profiles between groups. The number of patients with no emesis and no
      nausea during the 24-hour study period was significantly greater (p < 0.05) with
      ondansetron 4 mg compared with placebo. Prognostic factors for an increased
      likelihood of developing PONV in males included a history of motion sickness or
      previous PONV, patients undergoing nonorthopedic procedures, and surgeries
      lasting longer than one hour. Finally, 38% of patients experiencing PONV
      perceived PONV to be as, or more debilitating than, the aftereffects of surgery
      itself. CONCLUSIONS: Ondansetron 4 mg was more effective than placebo in
      preventing PONV in male outpatients. Males at potential risk for developing PONV
      include: (1) those with a history of motion sickness and/or PONV; (2) patients
      undergoing nonorthopedic procedures; and (3) procedures lasting longer than one
      hour. Such patients may benefit from receipt of a prophylactic antiemetic.
      Postoperative nausea and vomiting has a debilitating effect that can be
      differentiated by patients from the effects of surgery itself.

PMID- 8982893
TI  - Ethanol monitoring of the transurethral resection syndrome.
AB  - Ethanol monitoring is a fairly new method of assessing fluid absorption during
      transurethral resection of the prostate (TURP). By using an irrigating fluid
      containing a trace amount of ethanol, the absorption can be measured by expired
      breath tests. We describe a TURP in which large-scale absorption of irrigating
      fluid occurred despite the use of a pressure-warning device set at 10 cm H2O. The
      surgeon decided to terminate the operation because 1.0 liters of fluid had been
      absorbed over 10 minutes, and another 1.0 liter was absorbed during the 10
      minutes required to conclude the surgery. The high absorption rate suggests that
      continued resection would have promoted a severe transurethral resection
      syndrome. This was prevented by the indication given by the breath test, whereas
      the pressure-warning device failed to do so.

PMID- 8982894
TI  - Conus medullaris injury following both tetracaine and lidocaine spinal
      anesthesia.
AB  - Multiple reports of cauda equina syndrome and transient radicular nerve root
      irritation have suggested that lidocaine spinal anesthesia may be responsible. In
      this case report, a patient with a preexisting diabetic neuropathy received a
      partial block following a tetracaine spinal, which was followed by a lidocaine
      spinal. Following block resolution, a new conus medullaris syndrome was
      diagnosed. Because of the close proximity of the cauda equina and the conus
      medullaris, differentiation between these syndromes can be difficult. The
      preexisting diabetic neuropathy may have predisposed this patient to neurologic
      injury. The choice of a different local anesthetic drug with less neurotoxic
      potential such as bupivacaine may have prevented this injury.

PMID- 8982895
TI  - Venous air embolism during radical perineal prostatectomy.
AB  - An abrupt decrease in end-tidal carbon dioxide (CO2) occurred in an anesthetized
      male who was placed in the head down position during radical perineal
      prostatectomy. The end-tidal CO2 was restored after insertion of a wet pack into
      the operative site, which strongly indicated venous air embolism as the cause.
      Predisposing factors, detection, and treatment of venous air embolism in this
      setting are discussed.

PMID- 8982896
TI  - Cardiovascular collapse during anesthesia in a patient with preoperatively
      discontinued chronic MAO inhibitor therapy.
AB  - We describe a patient in whom long-term monoamine oxidase (MAO) inhibitor therapy
      was discontinued 20 days before surgery with general anesthesia. This patient
      developed severe perioperative hypotension after administration of 10 mg of
      bupivacaine through an epidural catheter, which was corrected only after potent
      vasopressor therapy. We attribute this hemodynamic instability to attenuation of
      this patient's sympathetic tone based on several mechanisms: (1) residual effect
      of long-term administration of MAO inhibitor that caused a decrease in the number
      of beta-adrenergic receptors (adrenergic subsensitivity due to receptor down
      regulation), (2) recovered MAO activity causing effective degradation of
      sympathetic amines, and (3) combined attenuating effects of general and epidural
      anesthesia on sympathetic tone.

PMID- 8982897
TI  - Central nervous system toxicity in a patient receiving continuous intrapleural
      bupivacaine.
AB  - A patient developed signs of central nervous system (CNS) toxicity during
      treatment of postthoracotomy pain with a continuous intrapleural bupivacaine
      infusion. This incident occurred after the patient's chest tube was clamped,
      without any decrease in the bupivacaine infusion rate. This is the first reported
      case of CNS toxicity in a patient receiving a continuous intrapleural bupivacaine
      infusion. Possible etiologies of this complication are discussed, as are ways to
      avoid such a complication in the future.

PMID- 8982898
TI  - Thrombolytic therapy for treatment of pulmonary embolism in the postoperative
      period: case report and review of the literature.
AB  - A patient with morbid obesity and insulin-dependent diabetes was admitted to the
      surgical intensive care unit, four days status postsurgical repair of an
      umbilical hernia. A pulmonary embolus (PE) was diagnosed by ventilation/perfusion
      scan and confirmed by transthoracic echocardiogram. A right ventricular ejection
      fraction/volumetric/oximetry pulmonary artery catheter revealed a very low
      ejection fraction and cardiac index. Systemic urokinase therapy was initiated and
      the patient improved considerably over the ensuing 12 hours. Anesthesiologists
      must be able to diagnose the signs and symptoms of PE and should be familiar with
      treatment modalities to reverse right ventricular dysfunction. Review of the
      literature regarding thrombolytic therapy in the perioperative period indicates
      potential benefit in select patients.

PMID- 8982899
TI  - Recall in the sedated ICU patient.
AB  - The effect of sedation on ICU patient recall is uncertain. Ensuring suppression
      of awareness and, particularly, recall, may prevent post-ICU psychological
      problems. Development of ICU sedation pathways and improved neurophysiologic
      monitoring techniques may help clinicians provide good levels of recall
      suppression and sedation when they are most needed by ICU patients.

PMID- 8982900
TI  - The pharmacokinetics of remifentanil.
AB  - Opioids decrease the sympathetic and somatic responses to noxious stimulation and
      can be given in high doses without negative inotropic effects, even in patients
      with impaired cardiac function. With currently available opioids, precise
      titration of dose to effect is difficult, and high doses result in drug
      accumulation and prolonged respiratory depression. Remifentanil is a new
      synthetic opioid with direct action on mu-opioid receptors. It has a rapid onset
      and short latency to peak effect. It is rapidly inactivated by esterases in both
      blood and tissues, resulting in a very short duration of action. The context
      sensitive half-life remains very short (3 to 4 minutes), independent of the
      duration of infusion. These characteristics facilitate titration of dose to
      effect and also allow the use of very high doses (ED99) without prolonging
      recovery from its effects. The duration of action of remifentanil has been found
      to be short, even in patients with renal or hepatic failure, although only low
      doses have been used in the studies published to date. The hydrolysis of
      remifentanil produces a metabolite with very weak opioid receptor activity that
      does not contribute to the effects of remifentanil. Possible disadvantages of the
      drug include (1) the need to mix the lyophilized drug with a diluent, (2)
      administration as a continuous infusion, (3) risk of rapid loss of analgesic and
      anesthetic effects if the infusion is interrupted accidentally, and (4)
      difficulty in judging the dose of another, longer lasting opioid that will be
      required to control postoperative pain without producing excessive ventilatory
      depression. Remifentanil is likely to be more expensive than other opioids, but
      its use may reduce overall costs if prompt recovery from its effects results in
      shorter stays in the operating room and recovery units.

PMID- 8982901
TI  - The proposal to certify nurse anesthetists.

PMID- 8982902
TI  - Fiberoptic intubation through the laryngeal mask airway.

PMID- 8982903
TI  - Drug packaging similarities require extraordinary vigilance.

PMID- 8982904
TI  - Percutaneous transtracheal jet ventilation.

PMID- 8982905
TI  - Pulmonary edema and naloxone.

PMID- 8982906
TI  - Reflectance pulse oximetry at the forehead of newborns: the influence of varying
      pressure on the probe.
AB  - OBJECTIVE: Transmission pulse oximetry (TPO) is not a practical method of
      intrapartum fetal monitoring of arterial oxygen saturation. Reflectance pulse
      oximetry (RPO) requires a sensor applied to the skin of the fetal head and may be
      a useful technique. During labor, various degrees of pressure will be exerted on
      the RPO sensor. Previous studies have shown that moderate pressure on the sensor
      can improve the RPO signal. At increasing pressure, however, blood flow
      underneath the sensor will be occluded. This study examines the influence of
      pressure applied to the RPO sensor on the signal from the forehead of healthy
      newborns as a model for the fetal situation. METHODS: After institutional
      approval, 12 healthy newborns were studied. The RPO probe was placed at the
      forehead. Pressure on the probe was increased stepwise from 0 to 80 mmHg, and the
      effect on the ratio between the relative changes of the red and infrared light
      intensities (R/IR, inversely related to oxygen saturation) and pulse sizes was
      evaluated. Additionally, the effect of firm pressure (> 150 mmHg) on the probe
      was evaluated. RESULTS: R/IR values remained virtually unchanged when pressure
      onto the probe was increased from 0 to 80 mmHg, although the standard deviation
      slightly decreased. The pulse size increased as pressure on the probe increased.
      During firm pressure on the probe (> 150 mmHg), plethysmographic signals remained
      detectable, but R/IR values markedly increased. CONCLUSIONS: In newborns, mild to
      moderate pressure on the probe has little influence on the RPO signal at the
      forehead. Even during firm pressure, RPO can be used to obtain pulsatile signals,
      that presumably derive from tissue underneath the skull, such as the cerebral
      circulation.

PMID- 8982907
TI  - Continuous gastric suctioning decreases measured esophageal temperature during
      general anesthesia.
AB  - OBJECTIVE: This study sought to determine whether continuous gastric suctioning
      influences esophageal temperature measurements. METHODS: This study evaluated 21
      patients scheduled for extremity or lower abdominal surgery. After induction of
      general endotracheal anesthesia, an orogastric tube, and esophageal and
      nasopharyngeal temperature probes were placed in functional positions. Baseline
      esophageal (Tes) and nasopharyngeal (Tnas) temperatures were recorded and the
      orogastric tube was placed on continuous suction. After the first 11 patients
      (Group I) were studied, 10 additional patients (Group II) were studied with more
      frequent data collection to improve the time resolution of temperature changes.
      Temperatures were recorded for patients in Group I at 2 and 10 min with
      suctioning and 10 min after cessation of suctioning. In Group II, temperatures
      were recorded at 1, 2, 5 and 10 min with suctioning and 10 min after cessation of
      suctioning. Analysis of data was performed using repeated measures analysis of
      variance and paired t-tests with the Bonferroni correction. RESULTS: In Group I,
      Tes decreased significantly from 35.9 +/- 0.2 degrees C (mean +/- SE) to 35.1 +/-
      0.4 degrees C at 2 min and 34.8 +/- 0.3 degrees C at 10 min of suctioning (p <
      0.01). Ten minutes after cessation of suctioning, Tes was not significantly
      different from the baseline measurement. Tnas did not change significantly over
      the 20 min observation period. In Group II, Tes continually decreased from 36.2
      +/- 0.1 degrees C to 34.8 +/- 0.3 degrees C after 10 min of suctioning (p <
      0.006) and returned to near baseline 10 min after cessation of suctioning. There
      was no significant change in Tnas over the 20 min observation period. CONCLUSION:
      We conclude that continuous gastric suctioning decreases esophageal temperature
      measurements. This phenomenon should be recognized as an artifactual change in
      esophageal temperature and not a reflection of core temperature.

PMID- 8982908
TI  - Computer simulation of cerebrovascular circulation: assessment of intracranial
      hemodynamics during induction of anesthesia.
AB  - OBJECTIVE: The purpose of this project was to develop a computer model of
      cerebrovascular hemodynamics interacting with a pharmacokinetic drug model to
      examine the effects of various stimuli on cerebral blood flow and intracranial
      pressure during anesthesia. METHODS: The mathematical model of intracranial
      hemodynamics is a seven-compartment, constant-volume system. A series of
      resistance relate blood and cerebrospinal fluid fluxes to pressure gradients
      between compartments. Arterial, venous, and tissue compliance are also included.
      Autoregulation is modeled by transmural pressure-dependent, arterial-arteriolar
      resistance. The effect of a drug (thiopental) on cerebrovascular circulation was
      simulated by a variable arteriolar-capillary resistance. Thiopental concentration
      was predicted by a three-compartment, pharmacokinetic model. The effect site
      compartment was included to account for a disequilibrium between drug plasma and
      biophase concentrations. The model was validated by comparing simulation results
      with available experimental observations. The simulation program is written in
      VisSim dynamic simulation language for an IBM-compatible PC. RESULTS: The model
      developed was used to calculate the cerebral blood flow and intracranial pressure
      changes that occur during the induction phase of general anesthesia. Responses to
      laryngoscopy and intubation were predicted for simulated patients with elevated
      intracranial pressure and non-autoregulated cerebral circulation. Simulation
      shows that the induction dose of thiopental reduces intracranial pressure up to
      15%. The duration of this effect is limited to less than 3 minutes by rapid
      redistribution of thiopental and cerebral autoregulation. Subsequent laryngoscopy
      causes acute intracranial hypertension, exceeding the initial intracranial
      pressure. Further simulation predicts that this untoward effect can be minimized
      by an additional dose of thiopental administered immediately prior to intubation.
      CONCLUSION: The presented simulation allows comparison of various drug
      administration schedules to control intracranial pressure and preserve cerebral
      blood flow during induction of anesthesia. The model developed can be extended to
      analyze more complex intraoperative events by adding new submodels.

PMID- 8982910
TI  - New anesthetic requires new vaporizers for safety.

PMID- 8982909
TI  - Basic principles of optical radiation and some common applications in anesthesia.

PMID- 8982911
TI  - "Incessantly under fire". Medical ethics in a material world.

PMID- 8982912
TI  - Pronator quadratus revisited.
AB  - The pronator quadratus muscle has been neglected to a great extent in the
      anatomical and functional literature. This study confirms the consistent presence
      of two distinct heads to the muscle, and defines the gross and microscopic
      anatomy. The functional significance of these heads has been studied using in
      vitro and in vivo techniques to demonstrate that the superficial head is the
      prime mover in forearm pronation, and that the deep head is a dynamic stabilizer
      of the distal radioulnar joint.

PMID- 8982913
TI  - Toe to hand transfer in children. Part 1: technical aspects.
AB  - Between 1988 and 1994 40 children (age range 9 months-14 years) with either
      congenital (85%) or acquired hand deformities underwent reconstruction by
      microvascular autotransplantation of one or more toes. Fourteen underwent a
      single toe transfer whilst 26 had two second toes transferred to one hand. In 14
      of these cases both second toes were transferred at one operation. Whether one or
      two toes were transferred, the children spent on average 9 days in hospital. None
      of the transfers failed but 75% of the children underwent staged additional
      surgery to improve appearance and function. Thirty-seven of the 40 children
      attended with their parents for follow-up examination by an independent surgeon,
      a physiotherapist and a clinical psychologist in order to evaluate the results
      and consequences of surgery. This paper presents the technical considerations for
      this surgery and examines the influence of the transfer on growth.

PMID- 8982914
TI  - Toe to hand transfer in children. Part 2: Functional and psychological aspects.
AB  - Forty children with congenital (85%) or acquired hand disorders underwent
      transfer of one or two toes to one hand. The children were reviewed with their
      parents and assessed for functional and psychosocial performance. There was some
      evidence that the older the child at the time of transfer, the better the range
      of motion. The passive range of motion was on average 60 degrees more than the
      active range of motion despite subsequent procedures such as tenolysis. All
      transfers recovered protective sensibility and the majority recovered good levels
      of two point discrimination and light touch perception. Almost all transfers were
      naturally incorporated into the use pattern of the limb for some or most of the
      time. Most parents and patients reported a very positive effect of this surgery
      on the child's psychosocial functioning.

PMID- 8982915
TI  - Impaired regeneration in rat sciatic nerves exposed to short-term vibration.
AB  - We have studied the effects of vibration on the regeneration capacity of the
      peripheral nerve. A rat model was used where one hind limb was subjected to
      vibration of defined magnitude and duration while the contralateral hind limb was
      not exposed to vibration. Seven days later, the sciatic nerves were transected
      bilaterally and cross-joined giving the following groups: group A, a proximal
      vibrated nerve end sutured to a non-vibrated distal nerve end; group B, a non
      vibrated proximal nerve end sutured to a distal vibrated nerve end, and group C,
      non-vibrated proximal nerve end sutured to a non-vibrated distal nerve end. The
      regeneration distances were measured 3, 6 and 8 days after surgery. The control
      group showed a normal linear outgrowth. The outgrowth in the two experimental
      groups was initially not different to controls but later became significantly
      different, indicating a retardation of outgrowth in these groups. It is concluded
      that short-term exposure to vibration can impair nerve regeneration after
      transection and nerve repair.

PMID- 8982916
TI  - Is vibration-induced white finger a reversible syndrome if vibration is stopped?
AB  - The purpose of the study was to investigate if vibration-induced white finger may
      be a reversible symptom after cessation of vibration exposure. Fifty-nine
      welders, previously employed by a ship building company and who had shown various
      levels of vibration-induced vasospastic symptoms in the hand were interviewed 5
      to 6 years after closure of the company. Out of the 43 patients exposed to no or
      insignificant vibration subsequently, 28 claimed improvement, 11 claimed
      unchanged problems and four complained of worse problems. Twelve of these
      patients had the cold provocation test repeated at follow up. One patient showed
      the same result as 5 years earlier, six showed improvement and five showed much
      improvement. Of 16 patients with continued vibration exposure none showed
      subjective improvement, nine claimed unchanged problems while seven patients were
      worse. It is concluded that vibration-induced white finger is not a progressive
      condition following cessation of exposure to vibration. On the contrary it may be
      static or even reversible to some extent.

PMID- 8982917
TI  - Tissue displacement is a causative factor in vibration-induced muscle injury.
AB  - The early skeletal muscle response to vibration stimulus at two different
      displacement levels was examined. Twelve rats were anaesthetized and the hind
      limb was exposed to vibration, 80 Hz, 63 micronsrms (root mean square) (group 1)
      and 40 Hz; 130 micronsrms (group 2) for 5 hours/day for 2 days. Cross-sectional
      areas of vibrated muscle fibres were significantly larger in group 2. Sizes of
      different fibre types were differently affected: the slow-twitch type 1 fibres
      were significantly enlarged in both groups, while the fast-twitch type 2 fibres
      demonstrated a mixed response pattern. Centrally positioned muscle fibre nuclei
      increased significantly after vibration in group 2. It is concluded that the
      level of tissue displacement is a crucial factor for development of vibration
      induced muscle injury.

PMID- 8982918
TI  - Complete avulsion of the palmar cortex of the distal phalanx.

PMID- 8982919
TI  - External fixation for comminuted phalangeal fractures. A biomechanical cadaver
      study.
AB  - The mechanical rigidity obtained by external fixation in a comminuted phalangeal
      fracture model was assessed and the results compared with two other types of
      internal fixation commonly used (lateral plate and crossed Kirschner wires) in a
      biomechanical cadaver study. Each fixation technique was tested in apex palmar
      bending, compression and torsion. The results showed that lateral plating
      provided the best rigidity in apex palmar bending and compression and that
      external fixation and Kirschner wires showed the same mechanical properties. For
      the torque test, external fixation provided the best rigidity.

PMID- 8982920
TI  - Fixation for comminuted phalangeal fractures. A biomechanical study of five
      methods.
AB  - The rigidities of five fixation methods have been studied with a comminuted
      phalangeal fracture model. Mechanical testing of compression, bending and torsion
      were performed for each fixation. Lateral plating with six screws seems to
      provide the most rigid fixation. If such lateral plating is not practicable, the
      four-Kirschner wire method would be a satisfactory alternative.

PMID- 8982922
TI  - Fractures of the distal radius and scaphoid.
AB  - Simultaneous fractures of the distal radius and scaphoid is an uncommon wrist
      injury. During the period 1980 to 1993, 23 patients with a median age of 39 years
      were treated for this injury. The median follow-up period was 7 years. All
      scaphoid fractures were undisplaced and located in the waist or distal third. An
      extraarticular distal radial fracture was observed in 15 wrists. A below elbow
      cast including the thumb was applied in 18 wrists for a mean duration of 9 weeks,
      and operative treatment was used in only 5 patients. All scaphoid fractures
      healed without complications. During conservative treatment there were three
      redisplacements of distal radial fractures. The final functional results were
      good in 18, fair in four, and poor in one patient. Because complications occurred
      at the distal radius we have changed our conservative treatment policy from a
      below elbow cast including the thumb to a dorsal splint for 6 weeks.

PMID- 8982921
TI  - Injectable calcium phosphate in the treatment of distal radial fractures.
AB  - An injectable material which hardened in situ to form a carbonated
      hydroxyapatite, Norian SRS (Norian Corp., Cupertino, USA), was used as the only
      treatment of unstable distal radial fractures in six patients. Except for an
      external dorsal splint for 2 weeks, no other treatment was used. The material
      maintained reduction except in one case in which there were technical problems
      during hardening and the material fragmented postoperatively. By 1 year all
      patients had a satisfactory clinical outcome. There was an early return of
      motion. The possibility of mobilization 1 or 2 weeks after the operation may
      reduce postoperative stiffness and increase short-term functional outcome.

PMID- 8982923
TI  - Herbert screw insertion in the scaphotrapezial joint. A cause of degenerative
      change?
AB  - The method of insertion of the Herbert screw for scaphoid fractures and its long
      term presence in the scaphotrapezial joint may predispose to degeneration in that
      joint. We examined a group of patients with long-term follow-up to assess this
      risk and found it to be insignificant.

PMID- 8982924
TI  - Absence of flexor carpi radialis.

PMID- 8982925
TI  - Scaphoid osteochondroma mimicking carpal coalition.
AB  - We present the case of a 10-year-old girl who presented with a block to wrist
      abduction. Plain radiographs of the wrist suggested a coalition between the
      carpal bones. A CT scan, however, revealed the presence of an osteocartilaginous
      lesion on the distal pole of the scaphoid. This was resected and histology showed
      it to be an osteochondroma.

PMID- 8982926
TI  - Superficial radial nerve compression due to a scaphoid exostosis.

PMID- 8982927
TI  - Pseudoaneurysm of the radial artery complicating excision of a wrist ganglion.
AB  - A case of pseudoaneurysm of the radial artery complicating excision of a wrist
      ganglion is reported. Tourniquet release prior to wound closure would have
      allowed detection and immediate treatment of the vascular injury.

PMID- 8982928
TI  - Explosion injuries of the hand. Spatial relationship and injury pattern.
AB  - Twenty-six hands in 25 male patients were treated for peace-time explosion
      injuries of the palmar aspect. All patients were examined after a mean interval
      of 7 (1-17) years. In order to establish a regional pattern for each injury the
      palmar surface of the hand was divided in 21 fields. For each field a score
      depending on the extent of injury was calculated. Comparing this regional score
      with the spatial relation between hand and exploding object resulted in six
      typical patterns depending on the grip during explosion. With knowledge of the
      three-dimensional relation between the hand and exploding object, the hand
      surgeon is prepared for potential problems during operation.

PMID- 8982929
TI  - "Through-glass" injuries.
AB  - This prospective trial collected all cases where injuries had resulted from the
      hand passing through or striking glass and had been referred to a hand injury
      service during 1 year. Eighty-seven cases were referred and the factors relating
      to these injuries were examined. A record was made of the structures damaged, the
      surgery performed and prevailing socioeconomic factors. These injuries were very
      costly in terms of morbidity, surgical effort and time, with significant resource
      implications. The study appears to confirm other reports that current legislation
      on glazing safety was too long delayed and is inadequate now that it is in place.

PMID- 8982930
TI  - Pyoderma gangrenosum severely affecting both hands.
AB  - We report a case of pyoderma gangrenosum affecting both hands simultaneously.
      Pyoderma gangrenosum affecting the hands is an extremely rare condition which may
      result in considerable tissue destruction. Management includes immunosuppressant
      therapy, treatment of associated medical conditions and minimal surgical
      intervention. Despite a high maintenance dose of corticosteroid and adequate
      control of coexisting ulcerative colitis and rheumatoid arthritis, tissue
      destruction in the hands spread rapidly in our patient. The key to the patient's
      dramatic improvement was the tissue biopsy suggesting pyoderma gangrenosum and
      the subsequent treatment with the cytotoxic immunosuppressant, azathioprine.

PMID- 8982931
TI  - The "S" Quattro in severe Dupuytren's contracture.
AB  - Postoperative traction, using the "S" Quattro external fixation device, improved
      the initial correction in 17 of 18 fingers treated by limited fasciectomy for
      severe proximal interphalangeal joint contracture in Dupuytren's disease.
      Unfortunately significant recurrence occurred in eight within 1 year and only
      five maintained improved function. Complications included infection, loosening,
      recurrence, stiffiness and amputation.

PMID- 8982932
TI  - Long-term results after segmental aponeurectomy for Dupuytren's disease.
AB  - Segmental aponeurectomy has been proposed as a less extensive procedure for the
      treatment of Dupuytren's disease to limit the incidence of wound complications
      and stiffness associated with wide dissections. Analysis of the late results
      showed that the operation brought a lasting correction of the contracture. In
      hands which did not show any sign of progression of the disease, the follow-up
      values were even slightly better than the immediate postoperative measurements.
      It also showed that the proportions of recurrences, extensions and hands free of
      the disease are similar to those after other procedures and that the type of
      operation does not appear to be related to the progression of Dupuytren's
      disease.

PMID- 8982933
TI  - Contraction of collagen lattices by cells from Dupuytren's nodules.
AB  - The aim of this study was to see if nodular cells in Dupuytren's disease differed
      from dermal cells in their contractile capacity and motility. Ten surgical
      specimens from patients with Dupuytren's disease and contracture of the finger of
      more than 45 degrees were harvested and the nodular cells were explanted and
      cultured. Dermal fibroblasts from the forearm were used as control cells. Both
      types of cell had the same growth pattern. The morphology on confocal laser
      scanning microscopy was also similar in both types of cell. Dermal control cells
      caused significantly more contraction of collagen lattices compared with
      fibroblasts from nodules of Dupuytren's contracture. The F-actin content was
      equal in both groups. Platelet derived growth factor, PDGF-BB (but not PDGF-AA),
      increased the chemotactic activity of both cell types, but there were no
      differences between them. The results indicate that at a late state of the
      disease cells from Dupuytren's nodules lose their contractile capacity and regain
      a phenotype resembling that of dermal fibroblasts.

PMID- 8982934
TI  - Rubber band constriction of the wrist.
AB  - We report the effects of rubber bands placed as decorative bands around the
      wrists of two infants by older children. These bands went unnoticed by their
      parents for several hours until swelling of the hand occurred. Early
      decompression of the carpal tunnel and fasciotomy of the dorsum of the hand are
      recommended. Education of the community is important in avoiding complications
      from placement of these rubber bands around an extremity.

PMID- 8982935
TI  - The effect of pulsed electromagnetic fields on flexor tendon healing in the
      rabbit.
AB  - A double-blind controlled trial of the effects of pulsed electromagnetic fields
      on flexor tendon healing in adult New Zealand White rabbits was performed. A
      pulse burst waveform, previously demonstrated to influence new vessel growth in
      the rabbit, was employed. No significant effect was observed on either the healed
      strength of the tendon repair or the adhesion formation between the repair and
      the surrounding tissues. The model used for examination of adhesion formation was
      reproducible and is recommended for further work on the adhesion formation of
      healing tendons.

PMID- 8982937
TI  - Tensile strength of cross-stitch epitenon suture.
AB  - Using a computerized tensiometer, the mechanical properties of two types of
      repair in the canine flexor digitorum superficialis tendon were examined. The
      slope and ultimate tensile strength of a cross-stitch epitenon suture were
      compared to those of a simple over-and-over running epitenon suture. Both
      epitenon sutures were combined with a modified Kessler core suture. Suture
      material was 6/0 monofilament nylon for the epitenon suture, and 4/0 braided
      polyester for core suture. Average relative values of individual ultimate tensile
      strength for the cross-stitch group was 245% compared to that for the running
      suture group. There was no discrepancy in slope between the two groups.

PMID- 8982938
TI  - A two-dimensional kinematic analysis of the distal radioulnar joint.
AB  - The triangular fibrocartilage and its function in the kinematics of pronation and
      supination in the distal radioulnar joint was studied. Measurements of the
      constituent parts of this joint in 11 cadavers showed that the palmar radioulnar
      ligament is at least 2 mm longer than the dorsal radioulnar ligament. Based on
      these measurements the movements of the joint were modelled in a two-dimensional
      kinematic chain. Predictions based on this chain could be confirmed by direct
      observation and videotaping dissections of joints of unfixed specimens and three
      dimensional reconstructions of a CT scan of a healthy volunteer. It could be
      concluded that (a) the dorsal part is tight during pronation and the palmar part
      during supination and (b) considerable asymmetrical translations, (dorsal
      translation being the largest) occur because of the length differences of the
      ligaments.

PMID- 8982936
TI  - Patterns of cellular activation after tendon injury.
AB  - Mechanisms which lead to disabling adhesions following flexor tendon surgery of
      the hand were investigated in a rabbit model which was used to assess the
      relative response of the cells of the synovial sheath, epitenon and the endotenon
      to injury. A transverse laceration, cutting through 50% of the tendon, was made
      just outside the synovial sheath on the flexor aspect of the flexor digitorum
      profundus tendon. The synovial sheath was preserved intact. Using monoclonal
      antibodies for localizing specific inflammatory markers, we were able to follow
      the response and activity of the synovial sheath, epitenon and endotenon with
      respect to these markers at various times after surgery. Our findings suggest
      that the synovial sheath and the epitenon are relatively more reactive in the
      early period after injury, as judged by a range of inflammatory indices with the
      notable exception of the expression of the potent neovascularizing agent, basic
      fibroblast growth factor (bFGF).

PMID- 8982939
TI  - Absence of nails with absent distal phalanges.

PMID- 8982940
TI  - Plating the palmar surface of the distal radius in shortening osteotomies for
      Kienbock's disease and Barton's fracture.

PMID- 8982941
TI  - Anatomical aspects of wrist denervation.

PMID- 8982943
TI  - Deletions in the survival motor neuron gene in Turkish spinal muscular atrophy
      patients.

PMID- 8982942
TI  - Review: preimplantation diagnosis of inherited disease.
AB  - Preimplantation diagnosis of inherited diseases has become possible with the
      techniques of in vitro fertilization, blastomere biopsy of the 6- to 10-cell
      embryo and DNA analysis of the single blastomeres. Disease-free embryos are
      selected for transfer to the uterus, thereby avoiding the need for termination of
      a fetus diagnosed as affected in prenatal diagnosis in the first or early-second
      trimester of pregnancy. The genetic indications for preimplantation diagnosis are
      theoretically the same as for prenatal diagnosis, but the defects must be
      detectable by the polymerase chain reaction. For X-linked recessive diseases,
      fluorescence in situ hybridization can be used as an alternative for the
      selection of female embryos. So far almost 40 healthy children have been born
      worldwide after preimplantation diagnosis for genetic disease. The possibilities
      and limitations of preimplantation diagnosis, especially in prevention of
      inherited disease, are discussed in this review.

PMID- 8982944
TI  - Skeletal muscle of patients with gyrate atrophy of the choroid and retina and
      hyperornithinaemia in ultralow-field magnetic resonance imaging and computed
      tomography.
AB  - Gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), an
      autosomal recessive disease, affects skeletal muscle in addition to the eye.
      Muscle biopsy samples show prominent type 2 muscle fibre atrophy. Atrophic fibres
      also contain accumulations of tubular aggregates in electron microscopy. To
      evaluate skeletal muscle involvement in detail, the thigh muscles of 7 patients
      with GA were examined using semi-open conchotome muscle biopsies, computed
      tomography (CT) and ultralow-field magnetic resonance imaging (MRI) at 0.02 T. In
      MRI, the T1 and T2 proton relaxation times were measured. Type 2 muscle fibre
      atrophy was found in all biopsy samples (100%) and tubular aggregates in 6 of the
      7 samples studied (87%). The CT density of the muscle tissue was increased in the
      only child of the study, decreased in 3 elderly subjects, and normal in the
      remaining 3 patients. Mean T1 relaxation times of the patients were decreased
      (135 +/- 5 ms) as compared to those of 6 healthy controls (157 +/- 12 ms) (p =
      0.002). The T2 relaxation time was slightly increased (40 +/- 3 ms) as compared
      to the controls (35 +/- 7 ms; not significant, p = 0.3). Our findings suggest
      that the thigh muscles of the patients with GA universally show changes in CT and
      MRI studies, but relaxation time measurements gave little additional information
      on the muscle metabolism.

PMID- 8982945
TI  - Rapid identification of PKU-associated mutations by multiplex DGGE analysis of
      the PAH gene.

PMID- 8982946
TI  - Late-onset holocarboxylase synthetase deficiency.
AB  - We report a 21-month-old female patient whose urine organic acid profile
      suggested a biotin utilization abnormality consistent with multiple carboxylase
      deficiency. For most previously reported patients, holocarboxylase synthetase
      deficiency has correlated with the early-onset variant of multiple carboxylase
      deficiency; conversely, biotinidase deficiency has been characteristic of the
      late-onset form. In vitro enzyme studies revealed that our patient suffered from
      holocarboxylase synthetase deficiency. We suggest that holocarboxylase synthetase
      deficiency should be considered in the differential diagnosis of older patients
      in whom there is suspicion of a defect in biotin metabolism.

PMID- 8982947
TI  - Plasma total odd-chain fatty acids in the monitoring of disorders of propionate,
      methylmalonate and biotin metabolism.
AB  - Total plasma odd-numbered long-chain fatty acids were analysed in patients with
      methylmalonic acidaemia (vitamin B12-responsive and unresponsive), combined
      methylmalonic acidaemia/homocystinuria (CblC), propionic acidaemia (both neonatal
      onset and late-onset), biotinidase deficiency and holocarboxylase synthase
      deficiency, as well as in hospital controls. Total odd-numbered long-chain fatty
      acids (C15:0, C17:1 and C17:0) were expressed as a percentage of total C12-C20
      fatty acids. Control values were 0.72% +/- 0.31% (n = 12). Normalization of the
      percentage of odd-chain fatty acids occurred in all vitamin-responsive patients,
      following the institution of vitamin treatment. In general the neonatal-onset
      propionic acidaemia and B12-unresponsive methylmalonic acidaemia patients had the
      highest plasma odd-chain fatty acid concentrations, which correlated with the
      clinical condition but not with the urinary excretion of methylcitrate or
      methylmalonate. Plasma odd-chain fatty acid concentrations and methylmalonate
      excretions in CblC patients reacted very well to vitamin B12 treatment, but with
      no clinical response. Measurement of plasma odd-chain fatty acids is of no value
      for the monitoring of defects of biotin metabolism.

PMID- 8982949
TI  - Ataxia associated with increased plasma concentrations of pristanic acid,
      phytanic acid and C27 bile acids but normal fibroblast branched-chain fatty acid
      oxidation.
AB  - Investigations of peroxisomal function were undertaken in an 8-year-old girl who
      developed motor difficulties at the age of 3.5 years and went on to develop a
      progressive ataxia and dysarthria. There were no other neurological abnormalities
      and she was of normal intelligence. Analysis of plasma very long-chain fatty
      acids revealed a normal C26 concentration and normal C24/C22 and C26/C22 ratios.
      Analysis of branched-chain fatty acids showed an elevated plasma phytanic acid
      concentration of 60 mumol/L (normal < 15) and a considerably elevated pristanic
      acid concentration of 50 mumol/L (normal < 2). Plasma concentrations of the C27
      bile acids 3 alpha, 7 alpha-dihydroxycholestanoic acid (DHCA) and 3 alpha, 7
      alpha, 12 alpha-trihydroxycholestanoic acid (THCA) and of the C29-dicarboxylic
      acid were also increased. We postulated that these results might be due to
      deficiency of the peroxisomal branched-chain acyl-CoA oxidase, but when oxidation
      of branched-chain fatty acids was studied in cultured skin fibroblasts it was
      found to be normal. Alternative explanations for the accumulation of branched
      chain substrates for peroxisomal beta-oxidation are discussed. Treatment with a
      low-phytanic acid diet arrested the progression of the ataxia and led to a slight
      improvement.

PMID- 8982948
TI  - Complementation analysis of systemic cytochrome oxidase deficiency presenting as
      Leigh syndrome.
AB  - Systemic cytochrome oxidase deficiency presenting as Leigh syndrome is a well
      defined biochemical entity. Although the enzyme defect is demonstrable in all
      tissues, clinical abnormalities are restricted to the central nervous system.
      Biochemical studies comparing rates of synthesis of cytochrome oxidase subunits
      with the steady-state levels of immunoreactive protein in the mitochondrial inner
      membrane suggest a defect in assembly or stability of the complex. Family studies
      suggest that the disease is inherited as an autosomal recessive and somatic cell
      genetic studies directly implicate nuclear genes. As there are likely to be a
      number of different nuclear genes involved in the synthesis, assembly and
      stability of the cytochrome oxidase complex, we have fused patient fibroblasts
      and analysed the heterokaryons for complementation of the enzyme defect in an
      attempt to define the extent of genetic heterogeneity in this condition. So far,
      three complementation groups have been defined, although the majority of patients
      fall into a single group.

PMID- 8982950
TI  - Co-cultivation of Niemann-Pick disease type C fibroblasts belonging to
      complementation groups alpha and beta stimulates LDL-derived cholesterol
      esterification.
AB  - Niemann-Pick disease type C (NPC) is a neurovisceral storage disorder with an
      unknown primary deficiency. Somatic cell hybridization experiments using human
      cultured fibroblasts have shown that two complementation groups (NPC-alpha and
      NPC-beta) are associated with the biochemical and clinical phenotypes comprising
      NPC. We identified the rarer complementation group NPC-beta originally using the
      technique of filipin staining as a marker for complementation. In this study we
      show that the esterification of cholesterol derived from the LDL pathway can be
      used as an isotopic assay. However, multinuclear hybrids exhibit a delayed
      induction in this pathway. Furthermore, we discovered that, in the presence of an
      LDL source, co-cultivation of fibroblasts belonging to NPC-alpha and NPC-beta
      stimulated cholesterol esterification.

PMID- 8982951
TI  - Evolution of the neuroimaging changes in fucosidosis type II.
AB  - We report on clinical and neuroradiological findings in two patients with
      fucosidosis type II; a 7-year-old Jordanian boy and a 3 1/2-year-old Anglo
      Canadian girl. This rare, autosomal recessive disorder is caused by deficiency of
      lysosomal alpha-fucosidase and is manifested clinically by progressive mental and
      motor deterioration, coarse facies, growth retardation, recurrent infections,
      dysostosis multiplex, angiokeratoma corporis diffusum, visceromegaly and
      seizures. Cranial CT and magnetic resonance imaging showed density and signal
      abnormalities in the thalamus, globus pallidus and internal capsules bilaterally,
      as well as progressive CT density alterations in supratentorial white matter
      including the internal medullary laminae of the thalami and the internal
      capsules.

PMID- 8982953
TI  - Congenital nephrotic syndrome: a novel phenotype of type I carbohydrate-deficient
      glycoprotein syndrome.
AB  - Type I carbohydrate-deficient glycoprotein (CDG) syndrome is a genetic
      multisystem disorder generally without overt renal problems. We report a neonate
      with neurological abnormalities and congenital nephrotic syndrome of diffuse
      mesangial sclerosis type. Serum transferrin isoelectric focusing showed the
      typical abnormalities of type I CDG syndrome. Normal transferrin focusing
      findings in other patients with similar renal problems excluded the possibility
      of a secondary biochemical phenomenon. The diagnosis of type I CDG syndrome was
      confirmed by demonstration of a deficiency of phosphomannomutase. No evidence of
      pontocerebellar atrophy was found in imaging or at autopsy. We conclude that
      congenital nephrotic syndrome may occur in type I CDG syndrome, and that this
      diagnosis should be considered in patients with congenital nephrotic syndrome.
      Absence of pontocerebellar atrophy does not exclude the diagnosis of type I CDG
      syndrome.

PMID- 8982952
TI  - A D255H substitution in the arylsulphatase A gene of two unrelated Belgian
      patients with late-infantile metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is an autosomal recessive disease of myelin
      metabolism caused by a deficiency in the lysosomal enzyme arylsulphatase A
      (ARSA). We have identified a new mutation in exon 4 of the ARSA gene of two
      unrelated Belgian patients with late-infantile MLD. The mutation predicts an
      aspartic acid-to-histidine substitution at position 255 in arylsulphatase A
      (D255H), in a highly conserved region among sulphatases. Transient expression of
      the mutation in COS cells did not show an increase in ARSA activity. Both
      patients were compound heterozygotes carrying the frequent splice site mutation
      in intron 2 (459 + IG -->A) on the other allele.

PMID- 8982954
TI  - Pulmonary infiltration in Niemann-Pick disease type C.

PMID- 8982955
TI  - Persistent glycolic aciduria in a healthy child with normal alanine-glyoxylate
      aminotransferase activity.

PMID- 8982956
TI  - Leigh syndrome due to pyruvate dehydrogenase E1 alpha deficiency (point mutation
      R263G) in a Spanish boy.

PMID- 8982957
TI  - Hyperglycinaemia in a child with carbohydrate-deficient glycoprotein syndrome
      type I.

PMID- 8982958
TI  - Neuronopathic and non-neuronopathic presentation of Gaucher disease in patients
      with the third most common mutation (D409H) in Spain.

PMID- 8982959
TI  - Medical life is worth living.

PMID- 8982960
TI  - Submandibular salivary gland fibrosis.
AB  - Although the salivary glands are the primary participants in the first stage of
      digestion, they are discussed infrequently by clinicians of every category.
      Rarely, are they mentioned in the physical examination of a patient's medical
      record. Nonetheless, these glands are of clinical significance and worthy of
      diagnostic evaluation. A brief review is given of submandibular salivary gland
      fibrosis concerning the anatomy, physiology, pathology, clinical aspects
      diagnosis, and its treatment.

PMID- 8982961
TI  - Blood, sweat and fear. "A classification of hematidrosis".
AB  - In order to verify the accuracy of the commonly used statement, "I sweat blood,"
      a survey of the literature in the subject of hematidrosis was made. Seventy-six
      cases were studied and classified into categories according to the causative
      factor. These were, component of systemic disease, vicarious menstruation,
      excessive exertion, psychogenic, and unknown. The psychogenic were further
      subdivided into those that occurred only one time, those that recurred and the
      stigmatics. Acute fear and intense mental contemplation were found to be the most
      frequent inciting causes. Hematidrosis is an extremely rare clinical phenomenon
      with only few instances reported to have occurred within the twentieth century.

PMID- 8982962
TI  - Breast cancer in the inner city: intensive efforts may be succeeding.
AB  - Breast cancer is a significant problem in a 518 bed government supported
      university hospital in New Jersey's largest city. The following records were
      reviewed: tumor registry abstracts of the 367 analytic breast cancer patients
      admitted from 1/1/91 to 12/31/92; the 455 participants in the Breast Cancer
      Detection Awareness Program (BCDAP) from 1987 to 1992; and the 460 breast
      biopsies performed from 1990 to 1992. Breast cancer is less common at this inner
      city hospital than in the U.S. in general; the stage is more advanced at
      presentation than in the U.S. overall; and the overall survival is only 54% at
      five years. Approximately 40% of the patients were African-American women from
      the inner city. Their median age was 53, seven years younger than the median age
      for diagnosis in the U.S. overall, and their five year survival was only 46%.
      Intensive efforts have recently produced improvement in the proportion of cases
      diagnosed at early stages (T0 and T1), but a decrease in mortality has not yet
      been seen.

PMID- 8982963
TI  - Sural nerve biopsy in vasculitic neuropathies: morphometric analysis of the
      caliber of involved vessels.
AB  - We performed histologic and morphometric analyses of the sural nerve in 13
      patients with vasculitic neuropathies. The ratio of vessels with vasculitis, the
      caliber of involved vessels, and pathologic changes of myelinated fibers were
      evaluated. In patients with polyarteritis nodosa (PN), rheumatoid arthritis (RA),
      and systemic lupus erythematosus (SLE), marked vasculitis with inflammatory cell
      infiltration and occlusion were observed in epineurial arteries greater than 100
      microns in diameter, and mild vasculitic changes were noted in arterioles 40 to
      100 microns in diameter. In vessels less than 40 microns, mild vasculitis with
      perivascular cuffing was noted in patients with RA and SLE, but not in PN. In a
      patient with microscopic PN, mild inflammatory cell infiltration was encountered
      around small vessels at diameters less than 40 microns as well as those greater
      than 100 microns. In a patient with nonsystemic vasculitic neuropathy, vasculitic
      changes were identified only in vessels less than 40 microns. In patients with
      Churg-Strauss syndrome (CSS), there were no distinct findings of vasculitis in
      any biopsy material. In conclusion, morphometric analyses of the caliber of
      involved vessels may be useful in the differential diagnosis and classification
      of underlying vasculitic neuropathies.

PMID- 8982964
TI  - Effects of physical therapy on immunological parameters in patients with
      cerebrovascular diseases.
AB  - The effects of physical therapy on immunological parameters were evaluated in 22
      patients (14 males, aged 68.1 +/- 9.9 years) with cerebrovascular diseases in a
      stable situation 3 to 6 months after the onset of stroke who were entered into a
      rehabilitation program in our hospital between 1990 and 1993. The proportion of
      CD4+ cells was significantly increased but that of CD8+ cells was decreased
      throughout the rehabilitation program, resulting in an increase in the ratio of
      CD4+/CD8+ cells. The lymphocyte response to phytohemagglutinin and concanavalin A
      was increased, while no significant differences were observed in CD3+ cells,
      natural killer cell activity, and serum levels of immunoglobulins, interleukin-1
      beta, interleukin-2 and interleukin-6. These findings suggest that repeated
      physical exercise may activate the immune system, especially T-cell function, for
      possible prevention of infectious diseases that are often complicated in patients
      with cerebrovascular diseases.

PMID- 8982965
TI  - Nutrient-induced thermogenesis and protein-sparing effect by rapid infusion of a
      branched chain-enriched amino acid solution to cirrhotic patients.
AB  - An increase in the resting energy expenditure (REE) on indirect calorimetry was
      observed by rapid intravenous infusion of a branched chain-enriched amino acid
      solution into cirrhotic patients. The increases resulted in nutrient-induced
      thermogenesis (NIT). The percentage of energy expenditure (EE) derived from
      protein decreased significantly with the infusion of the amino acids. The present
      pilot study demonstrates that branched chain amino acids can be utilized as
      energy substrates and a protein-sparing effect occurs in patients with liver
      cirrhosis.

PMID- 8982966
TI  - Leukemic transformation in three patients with polycythemia vera. Analysis of the
      clinicopathological features and N-ras gene mutation.
AB  - Thirty-three patients were diagnosed as having polycythemia vera (PV) from 1973
      to 1993 in our institution. Of these patients, three who had been treated with
      alkylating agents, progressed to acute non-lymphocytic leukemia (ANLL). Their
      physical findings and the laboratory data were similar to those patients who did
      not become leukemic. To investigate the association with leukemic evolution, we
      examined N-ras oncogene activation in those patients who progressed to acute
      leukemia. Point mutations in codons 12 and 13 were not always detected,
      suggesting that the N-ras gene did not influence occurrence of ANLL in our
      patients.

PMID- 8982968
TI  - Renal cell carcinoma presenting as a solitary anterior superior mediastinal mass.
AB  - Lesions of the anterior mediastinum typically include neoplasms of the thymus or
      thyroid, hemangioma, germ cell neoplasms, lymphoma and others. Renal cell
      carcinoma often presents with flank pain, hematuria, abdominal pain and/or fever.
      Chest cavity involvement by renal cell carcinoma typically manifests as pulmonary
      parenchymal disease with or without hilar lymph node involvement. We report an
      unusual presentation of renal cell carcinoma in a patient who presented with
      symptoms secondary to a large anterior mediastinal mass. A 64-year-old woman came
      to the hospital complaining of malaise, cough, dyspnea, weight loss and night
      sweats. Chest roentgenogram and computed tomography revealed a large anterior
      superior mediastinal mass without significant pulmonary parenchymal disease. She
      was also noted to have microscopic hematuria and a renal mass was found.
      Histology of both masses revealed renal cell carcinoma. This case suggests that
      renal cell carcinoma may merit consideration in the differential diagnosis of an
      anterior mediastinal mass and illustrates an unusual manner by which this lesion
      may present.

PMID- 8982967
TI  - Reduced thyroidal uptake of inorganic iodine in liver cirrhosis.
AB  - Thyroid function was investigated in patients with liver cirrhosis. 123I uptake
      after four hours was significantly reduced in the liver cirrhosis group (n = 19)
      compared with the control group (n = 16) (2.6 +/- 0.3% vs. 5.0 +/- 0.6%, mean +/-
      SE, p < 0.01). There was no significant difference in the blood inorganic iodine
      level between the two groups, and the blood 123I count after ingestion of 123I
      capsules was not significantly different between the two groups. The area of the
      thyroid was slightly smaller in the cirrhosis group. A thyroid stimulating
      hormone (TSH) loading test showed no significant difference in the TSH value at
      any time point. The serum albumin level and prothrombin time were significantly
      associated with the 4-hour thyroidal 123I uptake (p < 0.01, p < 0.05,
      respectively). We show that the thyroidal inorganic iodine uptake was reduced in
      patients with liver cirrhosis and this reduction correlates with the severity of
      liver cirrhosis. Possible mechanisms include abnormal thyroid iodine transport
      capacity or reduced turnover of thyroid hormones resulting in a reduction in
      iodine uptake in liver cirrhosis.

PMID- 8982970
TI  - An autopsy case of malignant lymphoma with a high serum CA 125 level occurring
      only in the brain and pericardium.
AB  - We report an autopsy case of a central nervous system (CNS) B-cell type lymphoma
      followed by cardiac tamponade. In this case, lymphoma cells which occurred
      primarily in the pericardium appear to metastasize to the brain and gradually
      increase in size in spite of control of the CNS lesion. The serum carbohydrate
      antigen 125 (CA 125) level was highly elevated and the autopsy findings showed
      the involvement of lymphoma only in the pericardium rather than the CNS, and the
      pericardium, not the tumor cells, was immunohistochemically positive for CA 125.
      Through this rare case, two things are suggested: first, the serum CA 125 level
      is elevated when B-cell type lymphoma infiltrates the coelomic epithelium;
      second, CA 125 is overproduced and secreted by the pericardium but not the
      lymphoma cells. Measurement of the serum CA 125 level may become a diagnostic
      marker for the infiltration of malignant lymphoma in the coelomic epithelium such
      as the pericardium, peritoneum or pleura.

PMID- 8982971
TI  - Asymptomatic multiple myeloma with concomitant neoplasms of two different
      origins.
AB  - A 63-year-old Japanese male with a four-year history of asymptomatic hypogamma
      globulinemia is presented. On admission, he had a mild bone marrow plasmacytosis
      at about 10% of the total nucleated cells, but had no anemia, no paraproteins nor
      bone lesions. Flow cytometric analysis showed a predominant proliferation of
      kappa chain-positive cells in the bone marrow and peripheral blood, and an
      increase in the proportion of natural killer cells in the peripheral blood.
      Furthermore, coexistent meningioma and transitional cell carcinoma of the bladder
      were subsequently found 9- and 15-months after the admission, respectively. We
      considered that a myeloma-induced, possible latent immunodeficiency may have
      allowed the additional tumor growth, and that this process may have been
      controlled by the cytotoxic subset of immune effector cells.

PMID- 8982969
TI  - Kaposi's sarcoma limited to penis treated with cobalt-60 radiotherapy.
AB  - We report a 78-year-old German man of neither Mediterranean nor Jewish lineage
      who developed Kaposi's sarcoma localized to his penis. An evaluation for
      retrovirus infection or other causes of immunosuppression was negative. The
      nodules responded to radiotherapy with cobalt-60, rapidly involuting. The patient
      has no evidence of Kaposi's sarcoma for over two years.

PMID- 8982972
TI  - Lutembacher's syndrome complicated by jaundice.
AB  - We encountered a 78-year-old female with jaundice induced by Lutembacher's
      syndrome, which, to our knowledge, is the first such case to be reported.
      Laboratory data and ultrasonographic examination revealed liver congestion with
      dilatation of the inferior vena cava and hepatic veins. A large atrial septal
      defect was found using two-dimensional echocardiography; the mitral valve area
      measured 1.6 cm2 by planimeter. Clinicians should be aware of congenital heart
      disease as an underlying cause of jaundice.

PMID- 8982973
TI  - Kallmann syndrome in females: gonadotropin versus GnRH to induce fertility.
AB  - Kallmann syndrome is characterized by hypogonadotropic hypogonadism and anosmia.
      We observed the improvement of gonadal failure upon exposure to gonadotropin, but
      not gonadotropin-releasing hormone, in the female patients.

PMID- 8982974
TI  - Classical conditioning of electrical self-stimulation of ventral tegmental area
      to brief visual stimuli in rats.
AB  - Two groups of rats with bipolar electrodes implanted unilaterally into the left
      ventral tegmental area were trained to lever-press for the response contingent
      electrical stimulation. After preliminary lever-press training, two types of
      daily sessions were held on 10 consecutive days: type T+, current intensity set
      at the Threshold level and each response was accompanied by the visual signal
      (stimulus lights above the lever briefly went off): and type ST-, current set at
      the Sub Threshold level and no visual stimuli. On day 11, combination of the
      subthreshold current intensities and stimulus lights previously associated with
      the threshold stimulation (session type ST+) resulted in a significantly elevated
      response rates compared to the performance under the subthreshold current without
      visual stimuli (session type ST-). The extinction and recovery of this phenomenon
      are also demonstrated.

PMID- 8982975
TI  - Real-time spike detection in EEG signals using the wavelet transform and a
      dedicated digital signal processor card.
AB  - This paper describes a complete real-time system for EEG signal analysis.
      Specific software and hardware have been designed to provide biologists with an
      efficient tool, which allows a complete study of the different states of
      vigilance as well as the paroxysmal activities. The analysis method which is
      based on the wavelet transform is first presented and compared to the standard
      spectral approach. The dedicated digital signal processor card, based on the
      Motorola 96002 processor chip, that has been designed to support real-time
      acquisition and real-time processing of EEG signals is then presented. We finally
      illustrate the proposed method by processing real EEG signals of rats, and show
      that it opens up new prospects in the domain of EEG-based diagnosis. We propose a
      new representation, called globalization, that provides a global view and better
      detection of paroxysmal activities.

PMID- 8982977
TI  - Complete transection of rat optic nerve while sparing the meninges and the
      vasculature: an experimental model for optic nerve neuropathy and trauma.
AB  - In this study we present a method to achieve a complete transection of optic
      nerve axons in adult rat, while preserving the vasculature and retaining the
      continuity of the meninges. Under deep anesthesia, the optic nerve of adult rat
      is exposed. Using specially designed instruments built from disposable glass
      microsampling pipettes, a small opening is created in the meninges of the optic
      nerve, 2-3 mm behind the eye globe. A glass dissector is introduced through the
      opening and is used to cut all the axons through the whole width of the nerve.
      Complete transection of the optic nerve axons was achieved, while retaining the
      continuity of the meninges and avoiding damage to the nerve's vascular supply.
      Transection was confirmed by transillumination showing a complete gap in the
      continuity of the nerve axons, and by both morphological and electrophysiological
      criteria. Nerve transection performed by the conventional technique leads to
      neuroma formation and hampers regeneration. Crush injury may cause nerve
      ischemia, which is detrimental to axonal recovery. Both of these disadvantages
      are avoided by the method of transection presented here. The opening created in
      the 'meningeal tube' can be used to inject substances that may be of benefit in
      recovery, rescue and/or regeneration of the injured axons. The model is
      particularly suitable for in vivo studies on nerve regeneration, and especially
      for screening of putative therapeutic agents.

PMID- 8982976
TI  - In vivo determination of extracellular brain ascorbate.
AB  - A quantitative method consisting of the modification of the zero net flux
      technique was used to determine the extracellular concentration of ascorbate. A
      carbon paste electrode (CPE) held at constant potential was combined with a
      microdialysis probe through which various concentrations of ascorbate were
      locally infused. In experiments with bilateral CPEs, one of which was combined
      with a dialysis probe, no difference was observed in either basal or stimulated
      ascorbate currents. Addition of different concentrations of ascorbate to the
      perfusion fluid produced rapid changes in the voltammetric current due to
      ascorbate oxidation. Irrespective of the concentration of ascorbate infused, the
      current returned to basal level when the perfusion was stopped. The return was
      found to be more rapid after infusion of concentrations of ascorbate higher than
      the extracellular concentration than after perfusion with ascorbate-free
      solutions. This demonstrates that homeostasis of ascorbate occurs in vivo. The
      calculated point of zero net flux was 416 +/- 66 microM (n = 6). This represents
      the extracellular concentration of ascorbate.

PMID- 8982978
TI  - An implantable electrical interface for in vivo studies of the neuromuscular
      system.
AB  - The purposes of this study were to develop and test an implantable interface that
      could be used for repeated temporary electrical connections between implanted
      stimulating and recording devices and external equipment. The implantable multi
      use interface (TIMI) consists of an implanted set of connectors and temporary
      percutaneous leads. The connector(s) and attached devices are implanted during a
      sterile surgery. For each experimental session, a percutaneous lead is introduced
      into each connector with a hypodermic needle. The external ends of the
      percutaneous leads are then connected to the desired equipment. After the session
      is finished, the percutaneous leads are removed. TIMIs have been used
      successfully with nerve cuff stimulating electrodes, a tendon force transducer
      and an electromyography electrode, and have been implanted with nerve cuffs for
      up to 14 weeks without failure. The advantages of the TIMI over the standard
      backpack connector include: (1) the internal location of the connector reduces
      the risk that the animal will damage the connector and (2) the temporary and
      relatively controlled nature of the percutaneous connection reduces the risk of
      infection associated with permanent percutaneous leads. The TIMI provides an
      inexpensive, simple and reliable electrical connection between implanted devices
      and external equipment.

PMID- 8982979
TI  - An approach to study molecular mechanisms involved in cytokine-induced anorexia.
AB  - Cytokines are released during pathophysiological processes. Cytokines (e.g.,
      interleukin-1 beta or IL-1 beta) induce neurological manifestations including
      anorexia. Here, we show an integrative approach to investigate the cellular and
      molecular basis of cytokine-induced anorexia. In this approach: (1) the chronic
      intracerebroventricular (icv) microinfusion (via osmotic minipumps) of cytokines,
      at doses that will yield estimated pathophysiological concentrations reported in
      the cerebrospinal fluid, is used. (2) General and computerized behavioral
      monitoring characterizes the microstructure of behavioral modifications induced
      by a cytokine, and the time course for cytokine action. (3) Brain regions and
      subregions (nuclei/areas) from animals exhibiting significant anorexia in
      response to cytokine(s) are dissected, and RNA and protein are isolated. (4) The
      profile of cytokine subsystems (ligands, receptors, endogenous inhibitors; for
      example, IL-1 alpha and beta, IL-1 receptor types I and II, and IL-1 receptor
      antagonist) is characterized in the same brain samples with polymerase chain
      reaction, sensitive RNase protection assays and immunoblots. (5) The relationship
      between changes in cytokine subsystems at the molecular level and cytokine
      induced anorexia within an animal is determined, and the general profile is
      analyzed with statistical methods. This approach is also pertinent to study
      neurotransmitter and neuropeptide profiles, and cytokine-cytokine, cytokine
      neuropeptide and cytokine-neurotransmitter interactions in vivo. The results show
      that this integrative and novel strategy can be used to study the molecular basis
      of anorexia and other neurological manifestations (e.g., fever, sleep changes)
      induced by cytokines.

PMID- 8982980
TI  - A new video path analyzer to monitor travel distance, rearing, and stereotypic
      movement of rats.
AB  - A new video path analyzer, described herein, monitors travel distance, rearing,
      stereotypic movement, rotation, and speed of rats simultaneously. The video path
      analyzer was equipped with a cage (black background, 50 cm long x 50 cm wide x 50
      cm high), camera, television screen, computer, and printer. A detailed
      description of this equipment is included. While studying the known activating
      effects of d-amphetamine on rats' behavior, we also evaluated the equipment for
      its maximum and accurate contribution to this study. Results indicate that this
      equipment compared to photocell equipment produced reliable data and offered the
      advantages of lower cost. It is expected to gain more popularity in the near
      future.

PMID- 8982981
TI  - A new ultrasonic method for measuring minute motion activities of rats.
AB  - A new ultrasonic method is presented for measuring the minute motion activities
      of rats. A pair of low-cost 40 kHz ultrasonic transducers are used to transmit
      ultrasound toward a rat and receive the ultrasound reflected from the rat. The
      relative motion of the rat modulates the phase difference between the transmitted
      and received ultrasound signals. An 8-bit digital phase meter was designed to
      record the phase difference signal which was used to reconstruct the relative
      motion waveform of the rat in an 8751 single-chip microcomputer. The
      reconstructed data are then sent to a PC-AT microcomputer for further processing.
      This method employs a spectrum analysis for the reconstructed data and can
      measure three minute motion activities including locomotor activity (LMA), tremor
      and myoclonia. Finally, the method has been tested with real animal experiments.
      The main advantages of this new method are that it is non-invasive, non-contact,
      low cost and high precision. This new method could also be profitably employed
      for other behavioral studies and offer potential for research in basic medicine.

PMID- 8982982
TI  - Nonlinear prediction as a tool for tracking the dynamics of single-trial
      readiness potentials.
AB  - The performance of a voluntary act is preceded by an intrinsic process of
      intention and preparation accompanied by specific patterns of scalp-recorded EEG.
      The baseline shift to negativity and the decrease of alpha and beta oscillations
      prior to movement performance are considered to reflect the motor preparation and
      are observable even in single-trial EEG records during repetitive voluntary
      movements. The single-trial features of these patterns are of importance since
      they would reflect the dynamics of EEG activity during movement performance
      throughout the experimental session. Since this process is very complex and its
      dynamics is unclear, we applied a more general approach, i.e. the method of
      nonlinear prediction (NP) recommended for detection of chaos in the behavior of
      nonlinear dynamical systems. The NP is based on a library of past patterns of the
      time series used to compute the prediction of future pattern. If the time series
      is chaotic, the correlation coefficient between predicted and actual values would
      decrease as a function of the prediction step. The NP was applied to EEG records
      containing readiness potentials (RPs) at Fz, Cz, Pz, C3 and C4 during repetitive
      voluntary finger flexion. Because of nonstationarity, the prediction and the
      library spanned the same time period. As a result (1) chaotic segments in EEG
      records were detected; and (2) the sharp jumps of the absolute error between
      predicted and actual values indicated instances of poor prediction, which were
      interpreted as indicating new stages of EEG activity related to the preparatory
      process of motor activity.

PMID- 8982983
TI  - Imaging developing neural morphology using optical coherence tomography.
AB  - Imaging technologies offer numerous possibilities to investigate the processes
      involved in neural development. The optical coherence tomography (OCT) technology
      is analogous to ultrasound backscatter microscopy except reflections of light are
      detected rather than sound. The OCT technology combines high-resolution in vivo
      imaging in a diode-based benchtop instrument capable of micron-scale resolution
      in transparent and non-transparent biological specimens. In this paper, we
      examine the potential of using OCT for the investigation of developing neural
      morphology. To demonstrate the capabilities of this technique in assessing neural
      development, we have chosen to image early normal and abnormal neural morphology
      in a common developmental biology model, Xenopus laevis. In vivo images clearly
      identify gross and subtle differences in neural structure and may offer an
      alternative to the costly and time-consuming process of repeated histological
      preparation for neural developmental studies. Because imaging can be performed
      rapidly and repeatedly, the morphological changes of single specimens can be
      followed throughout development. To illustrate the future potential of this
      technique, a state-of-the-art Cr4+:forsterite modelocked laser is used as a broad
      bandwidth light source to image individual cells in a developing specimen.

PMID- 8982984
TI  - Amperometric microsensors for monitoring choline in the extracellular fluid of
      brain.
AB  - Selective amperometric enzyme microsensors for monitoring low micromolar
      concentrations of choline in extracellular fluid of rat brain have been
      developed. Preparation of the choline microsensors involved the modification of
      carbon fiber microcylinder electrodes (10 microns diameter, 300-400 microns long)
      with a cross-linked redox-active gel containing horseradish peroxidase and
      choline oxidase. Rejection of the noise recorded from the choline microsensors
      implanted in living brain tissue improved the in vivo detection capabilities of
      the sensors. The microsensors and a differential detection scheme were used to
      estimate the basal concentration of choline in striatal tissue at 6.6 +/- 2.9
      microM and to measure changes in choline concentrations of 6.1 +/- 2.7 microM in
      vivo. The microsensors were also used to monitor choline produced following the
      injections of acetylcholine in vivo. Coinjections of neostigmine and
      acetylcholine significantly lowered the choline response recorded with the
      microsensors, confirming that the response following the injections of
      acetylcholine alone was due to the activity of endogenous acetylcholinesterase.
      Comparison of the maximal rate of decrease in choline concentration following the
      injections of 1 mM choline and 1 mM acetylcholine was used to estimate the rate
      of acetylcholine clearance from extracellular fluid through cholinesterase
      activity at approx. 2.5 microM/min.

PMID- 8982985
TI  - The relationship between the resistance of a membrane patch and predicted changes
      in total patch circuit resistance secondary to spontaneous or induced alterations
      in patch geometry.
AB  - The objective of this study was to determine the relationship between the
      magnitude of the membrane resistance in the free area of a cell-attached patch
      clamp recording and the change in total patch circuit resistance that would be
      produced by the introduction of a series resistance, such as would be observed
      upon acquiring a patch-clamped membrane vesicle. The results describe a method
      for determining the magnitude of the membrane resistance in the free area of a
      membrane patch, and demonstrate that: (a) at a given value of shunt resistance,
      areas of membrane with higher resistivity produce smaller proportional increases
      in total patch circuit resistance upon acquiring a membrane vesicle; and (b) a
      presumption of spherical vesicle formation provides a lower limit estimate of the
      membrane resistance. The described procedures and relationships are useful in
      developing new techniques for examining channel activity in membrane patches
      where individual events are below the present limits of detection, for examining
      changes in membrane resistivity and/or shunt resistance in patches undergoing
      cytoskeletal re-organization, and for assessing the potential influence of series
      resistance changes on single channel parameters in longer term cell-attached
      patch-clamp recordings.

PMID- 8982987
TI  - Metallized polymer fibers as leadwires and intrafascicular microelectrodes.
AB  - We have developed a process for producing fine, very flexible microwires suitable
      for use as small signal leadwires or nerve electrodes. The process incorporates
      metallization of high-performance monofilament polymer fibers to yield
      electrically conductive fibers with greatly improved flexibility over solid metal
      wires of similar strength. The metallization layers are produced by serial vacuum
      deposition of a 0.3 micron thick coating of three metals, titanium-tungsten
      (Ti/W), gold (Au), and platinum (Pt), onto monofilament, poly-p-phenyl
      terephthalate aramid fibers (Kevlar). The metallized fibers are then insulated
      with an approx. 1 micron thick layer of silicone elastomer. The result is a
      microlead with high electrical conductivity (linear resistance = 30 omega/cm),
      desirable interfacial properties, excellent mechanical stability and extremely
      high flexibility. These physical characteristics are appropriate for application
      as signal leadwires or recording/stimulating electrodes where small size and high
      flexibility are paramount. In this paper we report on the electrical and
      mechanical properties of these metallized fibers and demonstrate their use as
      intrafascicular electrodes for recording multi-unit neural activity in feline
      peripheral nerves.

PMID- 8982986
TI  - The use of in vitro preparations of the isolated amphibian central nervous system
      in neuroanatomy and electrophysiology.
AB  - In the present study an isolated preparation of the complete anuran central
      nervous system (CNS) is described which can be kept alive for several days and
      allows tracing, immunohistochemical and electrophysiological studies. A simple
      perfusion chamber is being used in which the isolated CNS preparation is
      superfused with oxygenated Ringer. The use of an isolated CNS has many advantages
      including: (1) virtually all areas are easily accessible at the same time without
      having the problem of blood vessels that hinder access; (2) large lesions and
      massive tracer applications are possible without survival problems of the animal,
      and tracers will not be translocated by blood circulation; (3) since pulsations
      caused by the pressure changes of blood circulation do not occur, intracellular
      recordings are comparatively easy and stable; and (4) this approach offers the
      possibility of working on the same brain for several days by storing the
      preparation in a refrigerator overnight at low temperatures, thus allowing
      extensive utilization of a single preparation and reduction in the number of
      experimental animals required. Some applications to the anuran auditory system
      illustrate that the isolated anuran CNS is well-suited for a variety of
      neuroanatomical and physiological techniques.

PMID- 8982988
TI  - Activity-based costing for clinical paths. An example to improve clinical cost &
      efficiency.
AB  - How much does this medical service or surgical procedure cost the hospital to
      provide? What is the most efficient clinical pathway that maximizes the quality
      of patient care while minimizing costs? More and more hospitals are discovering
      that they don't have solid answers to these critically important questions. In an
      age of managed care and capitation, however, it is imperative for management to
      know if the patient care services they provide are making or losing money-and by
      how much. This article discusses how a powerful new tool called activity-based
      costing (ABC) can be used to help hospitals accurately determine patient care
      costs. We show how to build a model that combines both clinical and financial
      data to measure how efficiently the operation allocates human, material and
      capital resources to provide its services. The modeling approach described in
      this article can be used to better analyze a wide range of important operational
      and financial issues, including: How to efficiently allocate resources, and what
      resources will be needed as patient demand changes-ideal for operational
      management and planning; How efficiently activities and processes are performed
      to meet patient needs-effective for measuring performance and improving quality;
      Determining clinical pathway profitability-essential for understanding where
      you're making or losing money; Cycle time, throughput and the impact of resource
      capacity constraints-critical for meeting patient demand; Costs of idle capacity
      important for using resources more efficiently. We will illustrate with an
      example how this modeling technique can be used to develop and implement
      efficient clinical pathways.

PMID- 8982989
TI  - Monitoring and assessing patient focused care performance.
AB  - This case study shares the experiences of converting a conventional financial and
      productivity performance system into one which measures, with greater detail,
      hospital operations undergoing changes in delivering patient care. An aggressive
      yet practical approach was used to meet management's main informational need for
      measuring the productivity and financial impacts of transitioning from a primary
      nursing care model (i.e., patient care being delivered exclusively by registered
      nurses) to a patient-focused care model while minimizing the impact of changing
      performance systems in the organization. Through this conversion, management can
      quickly detect and assess areas not complying with the patient-focused care
      model.

PMID- 8982990
TI  - Responsible choices for achieving reform of the American health system.
AB  - "Responsible Choices" identifies the actions the private sector and government
      should take to improve the American health system and accelerate and expand the
      health care revolution that is already underway. Policy proposals are made for:
      Medicare; Medicaid; reforming the tax treatment of health insurance; insurance
      reforms and expanding group purchasing opportunities; and improving the
      availability of comparative information on health benefit offerings, quality
      accountability, and cost and coverage information. The recommendations refocus
      the Jackson Hole Group's original managed competition proposals contained in "The
      21st Century American Health System" (1991).

PMID- 8982991
TI  - Determining the requirements for a computer-based patient record with an
      electronic meeting system.

PMID- 8982992
TI  - Physician productivity measurement, methodology and implementation.
AB  - These components are integrated into a single monthly report and distributed to
      all departments in the health system. Figures 2 and 3 illustrate the four main
      reports the system can generate. Shown are the overall facility report and the
      six month trend; the departmental report showing each department as compared to
      the facility; an individual department report that clearly illustrates each
      physician's contribution; and finally an individual provider report with trend
      analysis. These reports are modified slightly as required by each department, but
      the core information of RVUs/hour remains the basic comparative element. Each
      report contains comparisons of individual providers within their specialty,
      department or group, and at the facility and system level. Each department with
      specific needs has the report prepared to meet these needs, yet the entire
      facility follows a single standard to make inter-department comparisons
      meaningful. The information available on each individual report includes: Month.
      Number of patient visits. Number of unique patients. Average Number of visits per
      patient. Charges. Part A and Part B worked hours. Paid hours. RVUs generated per
      worked hour. Productivity measured against. The providers department average. The
      total group average. Year to date averages. Graphical depiction of RVUs. Hour
      with trend line. The department summary contains similar information while the
      department detail report provides a means to easily compare providers within the
      department against each other and the group as a whole. The overall BMERF report
      uses summary information from each department and provides a graphical indication
      of how each department is performing.

PMID- 8982993
TI  - Quality infrastructure: the key to implementing a total quality program in a
      clinical care setting.
AB  - The implementation of total quality principles and practices in health care
      requires a clear recognition of the physician's unique role in the industry. The
      author addresses the implementation of a total quality program in an 80-physician
      clinical care setting. The program's success is linked to the development of a
      supportive quality infrastructure that effectively accommodates this unique role.

PMID- 8982994
TI  - Switchboard simulation to improve productivity and customer service.
AB  - An application of classical industrial engineering/operations research techniques
      (i.e., multichannel queueing analysis) and detailed workload distribution data.
      An analytic simulation model developed on a personal computer (PC) is used with
      interactive analysis to develop switchboard coverage requirements and optimal
      staffing schedules by time of day and day of week. This represents a tangible
      example of how classical techniques can be used with newer approaches and a close
      working relationship between the analyst and line management, to solve a
      practical problem of optimizing both productivity and customer service quality.

PMID- 8982995
TI  - Selling high quality and low cost: market conditions and successful quality
      improvement projects.
AB  - Many potentially useful health care improvement projects fail to achieve much
      improvement. Even a technically excellent project can fail because, under certain
      conditions, economic factors in the health care market do not support high
      quality and low cost. Most health care markets evolve from the traditional fee
      for service market through a consolidation phase into risk shared market. At each
      phase, payment mechanisms will support specific quality and productivity
      improvement projects and discourage others. For example, the implementation of
      critical paths/clinical protocols is not supported until the majority of payers
      pay a fixed cost per illness or covered life. Prior to that point, loss of income
      for the hospital and/or physicians will inhibit successful implementation.
      Maximum quality and productivity improvements outcomes can be achieved with
      minimum efforts when project leaders understand the maturity of their
      organization's market, and strategic needs. This paper will review the types of
      payment systems (fee for service, discounted fee for service, and risk shared
      payments) and identify the types of projects that maximize benefit to the
      stakeholders involved.

PMID- 8982996
TI  - In vitro changes in non-facial human skin following CO2 laser resurfacing: a
      comparison study.
AB  - BACKGROUND AND OBJECTIVE: We evaluated the physical changes in human skin
      following CO2 laser cutaneous resurfacing with either the Sharplan SilkTouch
      handpiece or the Coherent UltraPulse laser. STUDY DESIGN/MATERIALS AND METHODS:
      Three-hundred five human tissue samples and matched controls were used. Up to
      five laser passes were performed per specimen. Parameters evaluated included:
      lateral skin shrinkage, transient temperature change, isometric tension
      development, elasticity change, and histologic change. RESULTS: Skin shrinkage
      increased in direct proportion to laser pass number. Isometric tension
      exponentially increased and elasticity exponentially decreased with successive
      laser passes. The zone of thermal denaturation for the SilkTouch handpiece was
      115 +/- 15 microns, and was independent of laser pass number. The zone of thermal
      denaturation was patchy for the UltraPulse laser treatments, regardless of pass
      number. A greater temperature increase was also measured for SilkTouch
      irradiation than with the UltraPulse laser. CONCLUSION: The observed alterations
      in tissue length, tension development, and elasticity obtained with SilkTouch or
      UltraPulse treatment may contribute to the changes in clinical appearance
      associated with laser cutaneous resurfacing. Our findings support a role for
      extracellular matrix contraction in the mechanism of action for CO2 lasers in
      cutaneous resurfacing.

PMID- 8982997
TI  - Measurement and modeling of thermal transients during Er:YAG laser irradiation of
      vitreous.
AB  - BACKGROUND AND OBJECTIVE: We investigated the transient thermal behavior of
      vitreous in order to understand the local thermal effects of laser output, and to
      predict the potential for unintentional injury during Er:YAG laser vitreoretinal
      surgery. STUDY DESIGN/MATERIALS AND METHODS: The output of a free-running Er:YAG
      laser (2.94 microns, 300 microseconds FWHM) was delivered through a fiberoptic
      and applied to en bloc samples of bovine vitreous. Temperature was measured with
      ultrafine thermocouples. RESULTS: For 6 mJ pulse energy at 10 Hz, a temperature
      rise of 20 degrees C is measured 500 microns from the laser tip. The temperature
      rise is localized with a rapid fall-off greater than 1 mm from the energy source.
      At constant time-averaged laser power, the temperature profile is independent of
      repetition rate. Our finite-difference model generates results qualitatively
      consistent with measured data and allows for investigation of the influence of
      thermophysical parameters on heat transfer. CONCLUSION: Thermal injury to ocular
      structures should be limited during intravitreal application of Er:YAG laser
      energy.

PMID- 8982998
TI  - Threshold and ablation efficiency studies of microsecond ablation of gelatin
      under water.
AB  - BACKGROUND AND OBJECTIVE: Laser thrombolysis is the selective ablation of
      thrombus occluding vessels by microsecond pulsed laser irradiation. To achieve
      efficient ablation of thrombus, the optimal wavelength, spot size, and pulse
      energy need to be determined. STUDY DESIGN/MATERIALS AND METHODS: A gelatin-based
      thrombus model confined in 3 mm inner diameter tubes was ablated under water
      using a 1 microsecond pulsed dye laser. Wavelength studies were conducted by
      varying the absorption of the gelatin between 10-2000 cm-1 corresponding to the
      waveband between 400-600 nm on the absorption spectrum of thrombus. A unique
      spectrophotometric method was developed to measure the ablated mass. An acoustic
      method was used to measure ablation thresholds under water as a function of
      absorption. RESULTS: The mass removed per pulse per unit energy was nearly equal
      over an absorption range of 100-1000 cm-1 at pulse energies above threshold. Mass
      removal increased linearly with pulse energy but did not have a direct
      relationship with radiant exposure. Ablation thresholds indicate that the gelatin
      needed to be heated only to 100 degrees C for ablation to commence. Ablation
      masses measured were an order of magnitude higher than those predicted by thermal
      ablation models. CONCLUSION: The results suggest that any wavelength between 410
      590 nm can be used for effective thrombolysis. The ablation efficiency depends on
      the total energy delivered rather than the radiant exposure. The high ablation
      efficiencies suggest a dominance of the mechanical action of vapor bubbles over
      thermal ablation in the ablation process.

PMID- 8982999
TI  - Laser irradiation of biological tissue through water as a means of reducing
      thermal damage.
AB  - BACKGROUND AND OBJECTIVE: Reduction of thermal damage inbred with laser surgery
      is an ongoing challenge. The cavitation effect has been shown to facilitate the
      transmission of a laser beam through the otherwise opaque water layer. We suggest
      that by immersing the target tissue in water during laser surgery, thermal damage
      will be diminished. STUDY DESIGN/MATERIALS AND METHODS: A method of irradiating
      tissue by CO2 laser through a layer of a few millimeters of water is described. A
      series of experiments was conducted on fresh bovine cornea immersed in water or
      in air, histology of thermal damage was compared. RESULTS: We were able to show
      that irradiation of tissue immersed in water reduces the thermal damage caused to
      the area surrounding the incision as compared to the damage caused during
      irradiation of tissue in air (P < 0.001). CONCLUSION: Laser surgery of tissue
      immersed in water can reduce the inbred thermal damage. Application of this
      method to clinical use may result in precise, clean cutting, and enable the use
      of CO2 laser through water.

PMID- 8983000
TI  - Water vaporization from heated tissue: an in vitro study by differential scanning
      calorimetry.
AB  - BACKGROUND AND OBJECTIVE: The heat balance equation is central to modeling laser
      vaporization of tissue. Because about 70% of tissue is water, energy loss due to
      water vaporization becomes an important consideration in modeling. In this study,
      the rate and pattern of water vaporization from various animal tissues studied by
      differential scanning calorimetry (DSC) are reported. STUDY DESIGN/MATERIALS AND
      METHODS: DSC thermograms of fresh muscle, liver, and kidney tissues were made at
      heating rates of 2 degrees C/min, 5 degrees C/min, and 10 degrees C/min in the
      temperature range of 30-150 degrees C. Thermograms of vacuum-dried muscle sample
      were also made to establish that the endotherms obtained were essentially due to
      the water in the tissue. RESULTS AND CONCLUSION: Two broad peaks-one below and
      the other above 100 degrees C-are seen in all the endotherms. The peaks are
      attributed to the structural and compositional features of tissue and tissue
      water. The two-stage vaporization pattern has importance in modeling tissue
      heating by a continuous-wave Nd:YAG laser.

PMID- 8983001
TI  - Comparison of continuous versus pulsed CO2 and Nd:YAG laser-induced pulmonary
      parenchymal lung injury in a rabbit model.
AB  - BACKGROUND AND OBJECTIVE: Laser techniques have recently been described for
      treatment of patients with emphysema and bullous lung disease. Laser exposure of
      the pulmonary parenchyma during these procedures is complicated by laser-induced
      lung injury with substantial associated morbidity. Animal investigations are
      needed to develop methods that reduce lung injury. We hypothesized that the depth
      of injury could be reduced by pulsing laser exposures, with the goal of limiting
      thermal effects to more superficial tissue levels. In this study, we compared
      acute and chronic histologic injury resulting from pulsed- versus continuous-mode
      CO2 and Nd:YAG laser pulmonary parenchymal exposures in rabbits. STUDY
      DESIGN/MATERIALS AND METHODS: A total of 40 New Zealand White (NZW) rabbits
      underwent thoracotomy followed by exposure with CO2 laser (n = 10 continuous vs.
      n = 10 pulsed at 250 Hz with duty cycle 0.15 ms) or ND:YAG laser (n = 10
      continuous vs. n = 10 pulsed at 10 Hz with duty cycle 0.10 sec) to the visceral
      pleural surface using 1 minute of laser exposure (5 watts, defocused to 70 W/cm2
      power density) to the exposed lung surface. Rabbits were sacrificed at 4 and 21
      days post-injury, and lungs were examined histologically. RESULTS: CO2 and Nd:YAG
      laser treatment resulted in substantial pulmonary parenchymal injury. While CO2
      laser-induced damage was distinct from Nd:YAG histologically, pulsed-mode laser
      exposures did not reduce lung injury for either laser. Acute edema occurred to
      depths of 1180 +/- 338 microns for continuous-mode CO2 laser exposures compared
      to 1,340 +/- 430 microns in pulsed mode (p = .77). For Nd:YAG laser exposure,
      acute edema depth was 750 +/- 748 microns continuous versus 1120 +/- 367 microns
      pulsed mode (p = .65). Chronic lung fibrosis depth was 450 +/- 164 microns for
      CO2 continuous mode compared to 575 +/- 170 microns in pulsed mode (p = .61).
      Lung fibrosis depth for Nd:YAG was 550 +/- 96 microns, continuous versus 484 +/-
      180 microns pulsed mode (p = .76). CONCLUSION: The similarity in injury between
      pulsed- and continuous-mode exposures suggests that thermal relaxation times are
      long relative to the selected pulse frequencies in intact living rabbit lungs.
      Alternatively, brief high-energy pulsations may increase focal temperatures with
      a tendency to increase injury depth relative to the penetration of the laser
      light. Thus, pulsed laser modes in these settings appear to be ineffective in
      reducing laser-induced lung injury in clinical settings.

PMID- 8983002
TI  - Effects of continuous-wave laser systems on stapes footplate.
AB  - BACKGROUND AND OBJECTIVE: The aim of the present study was to clarify which of
      the presently available continuous-wave laser systems are best suited for
      application in stapes surgery. STUDY DESIGN/MATERIALS AND METHODS: Isolated human
      stapes and bovine compact-bone platelets were used to investigate the connections
      between the parameters of various laser systems and their effects on bone tissue.
      The purpose was to optimize the laser parameters required to achieve a
      perforation measuring 500 microns to 600 microns in diameter. Three different
      laser systems were applied: the argon and CO2 laser in continuous wave (cw) mode
      and the CO2 laser in superpulse mode. RESULTS: The suitability of the argon laser
      for stapedotomy is doubtful in view of the lower absorption coefficient of the
      stapes for the argon beam and the considerable influence which the degree of
      pigmentation of the irradiated medium exerts on its effect with the resultant
      poor reproducibility of the perforation diameter. The beam of the CO2 laser is
      far better absorbed at the footplate than that of the argon laser. This results
      in higher effectivity, lower thermic side effects, and better reproducibility of
      the perforation. The two modes of the CO2 laser do not show any appreciable
      differences. CONCLUSION: The experimental results presented indicate that the CO2
      laser in cw and superpulse mode is the most suitable of the systems now
      clinically applied in stapes surgery.

PMID- 8983003
TI  - Effect of laser pulse repetition rate and pulse duration on mast cell number and
      degranulation.
AB  - BACKGROUND AND OBJECTIVE: Mast cell activation by low-level laser therapy (LLLT),
      leading to degranulation and the release of mediators, may be one of the
      mechanisms by which LLLT can accelerate tissue repair in mammals. The objective
      of this work, part of an investigation to determine the optimum parameters for
      increasing mast cell number and degranulation in injured skin, was to determine
      the effect of different pulsing frequencies of LLLT. STUDY DESIGN/MATERIALS AND
      METHODS: Partial-thickness wounds in anaesthetized adult male Wistar rats were
      irradiated immediately after injury with monochromatic coherent light (wavelength
      820 nm) pulsed at either 2.5, 20, 292, or 20,000 Hz at an average power density
      of 800 mW/cm2 for 27 seconds; the energy density was 21.6 J/cm2. The effects on
      mast cell number and degranulation were assessed 2 hours post-treatment by
      counting the numbers of intact and degranulated mast cells in Carnoy-fixed,
      toluidine blue-stained, sections of irradiated and sham-irradiated wounds.
      RESULTS: The total number of mast cells was increased significantly (P < 0.05) by
      all the frequencies when compared to the sham-irradiated group, but there was no
      significant difference between frequencies (P > 0.05). However, although the
      number of degranulated mast cells was higher in all laser-treated wounds, in
      comparison with the sham-irradiated group, only the 20 Hz (pulse duration 45 ms)
      and 292 Hz (pulse duration 3 ms) frequencies were significantly effective (P <
      0.05). CONCLUSION: Increase in mast cell number is not pulsing frequency
      dependent, whereas degranulation is.

PMID- 8983004
TI  - In vitro pulp chamber temperature rises associated with the argon laser
      polymerization of composite resin.
AB  - STUDY DESIGN/MATERIALS AND METHODS: This in vitro study was performed upon 50
      extracted human molars that provided the occlusal surfaces for standard class I
      preparations. The cavity floor of the 20 specimens was covered with zinc
      phosphate cement and the teeth were sectioned transversally at or below the
      cementoenamel junction. In some specimens pulp tissue was removed from the pulp
      chamber. The cavities of all specimens were filled with composite resin, and the
      resin was cured with an argon laser. RESULTS: A statistically significant
      difference in the rise in temperature was obtained only in the temperature of
      dentin roof of the pulp chamber between the specimens with (2.2 degrees C) and
      without (3.1 degrees C) cement base (P < .05). There was no significant
      difference in the temperature of the pulp tissue between specimens with (2.7
      degrees C) and without (2.2 degrees C) base cement. The peak temperature of the
      composite surface was 13.8 degrees C. CONCLUSION: These data indicate that argon
      laser curing may be a method of choice for polymerization of the composite resin.

PMID- 8983005
TI  - Interstitial diode laser hyperthermia in the treatment of subcutaneous tumor.
AB  - BACKGROUND AND OBJECTIVE: Interstitial Laser Hyperthermia (ILH) has been
      investigated since the early 80s in the treatment of deep seated tumors. The
      purpose of this study was to evaluate the efficiency of diode ILH (830 nm) in a
      subcutaneous tumor model. STUDY DESIGN/MATERIALS AND METHOD: The antitumoral
      effect of diode ILH was assessed in a randomized study performed on 80 Swiss
      nu/nu mice. The tumor model was a subcutaneously implanted HT29 colonic
      carcinoma. The animals were assigned to four groups of 20 mice: Groups 1 and 3
      were treated by ILH, groups 2 and 4 were not treated (control groups). Tumors
      were removed on day 3 in groups 1 and 2, and on day 30 in groups 3 and 4. The
      treatment was performed on tumors of 8 mm in diameter and a volume of 140 mm3. A
      laser irradiation of 360 J (power: 0.2 W; irradiation time: 1800 s) was delivered
      through a 300 microns optical fiber implanted in the tumor. The laser parameters
      insured temperatures of 46 degrees C in the central part of the tumor and 42
      degrees C at the periphery. Tumor features were evaluated on day 3 and day 30.
      RESULTS: Untreated tumors grew rapidly up to a mean volume of 241 mm3 on day 3
      (group 2) and 2,000 mm3 on day 30 (group 4). Treated tumors regressed to a mean
      volume of 32 mm3 on day 3 (group 1). On day 30, 40% of the tumors had totally
      disappeared and 60% showed partial response with small and peripheral residual
      tumor of 172 mm3 on an average, as to say 11.2 times smaller than in group 4.
      CONCLUSION: ILH with a low power 830 nm diode laser is an efficient treatment of
      subcutaneous tumor model. Partial responses are attributed to an insufficient
      heating at the tumor periphery. More precise control of the peripheral tumor
      temperature will improve the ILH results.

PMID- 8983007
TI  - Effect of low-power He-Ne laser on fracture healing in rats.
AB  - BACKGROUND AND OBJECTIVE: Helium-Neon (He-Ne) laser radiation has been found to
      accelerate fracture healing in laboratory animal models as well as in cultures of
      cells involved in this process. We investigated the radiological, biomechanical,
      and histological effects of He-Ne radiation on fracture healing in a rat model.
      STUDY DESIGN/MATERIALS AND METHODS: Sixty-two rats underwent bilateral open
      osteotomies of the tibiae followed by internal fixation with intramedullary
      wires. The right leg received He-Ne laser radiation of 0, 2, or 4 Joules every
      other day for 2 to 6 weeks while the left leg served as a control. RESULTS:
      Radiological and histological examinations of the osteotomy sites failed to show
      any enhancing effect of He-Ne laser radiation on the bone healing process.
      Biomechanically, the irradiated bones of two of the six test groups were
      significantly weaker than the controls. CONCLUSION: These results fail to support
      the previously reported enhancing effect of He-Ne laser radiation on fracture
      healing.

PMID- 8983006
TI  - Comparison of sensitivity towards photodynamic therapy of cutaneous resident and
      infiltrating cell types in vitro.
AB  - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) combines photosensitizers
      absorbing light in the visible spectral region and irradiation with light of
      corresponding wavelengths. We analysed the sensitivity of cell lines established
      from resident cutaneous cells and from transformed lymphocytes towards PDT. STUDY
      DESIGN/MATERIALS AND METHODS: PDT was performed employing either 630 or 662 nm
      light or polychromatic red light (600-700 nm) and photosensitizers Photosan-3,
      delta-aminolevulinic acid, or methylene blue. Proliferation measured by 3H-TdR
      uptake was determined in human immortalized keratinocytes (HaCaT) and mouse
      fibroblasts (NIH/3T3) in comparison to human transformed T-(HuT78) and B
      lymphocytes (RA1). Additionally, uptake of the photosensitizers was estimated
      employing video-intensified fluorescence-microscopy (VIFM). RESULTS: Depending on
      the photosensitizer tested HaCaT and NIH/3T3 exhibited an ED50 up to 10-fold as
      high as the lymphocytic lines. Polychromatic red light was at least as effective
      at inducing photodynamic reactions as 630 or 662 nm light. VIFM revealed a
      positive correlation between sensitivity of a given cell type towards PDT and
      uptake of the photosensitizers. The differential uptake observed in vitro was
      confirmed in vivo: A photosensitizer applied topically on a lesion of a patient
      with mycosis fungoides was found to accumulate preferentially in the lymphocytic
      infiltrate. CONCLUSION: Selective topical polychromatic PDT seems to be a
      feasible goal for the treatment of cutaneous lymphomas.

PMID- 8983008
TI  - Low power laser irradiation reduces ischemic damage in hippocampal slices in
      vitro.
AB  - BACKGROUND AND OBJECTIVE: Low power laser irradiation has been reported to reduce
      injury, promote regeneration, and produce analgesia. While the mechanism is
      unknown, one hypothesis is that light produces free radicals, which have a
      beneficial effect at low concentrations. STUDY DESIGN/MATERIALS AND METHODS: We
      have investigated the effects of low power laser irradiation on the loss of
      electrical excitability of hippocampal brain slices after a transient exposure to
      a perfusion medium lacking oxygen and containing reduced glucose concentrations.
      Injury in this system is known to result at least in part from free radical
      production. RESULTS: Low power laser irradiation increased the time required for
      loss of excitability and increased recovery from the ischemic injury.
      CONCLUSIONS: Low power laser irradiation has acute protective effects against
      ischemic damage in brain slices.

PMID- 8983009
TI  - Anisotropy of radiance in tissue phantoms and Dunning R3327 rat tumors: radiance
      measurements with flat cleaved fiber probes.
AB  - BACKGROUND AND OBJECTIVE: The goal of this study is to determine if flat cleaved
      fiber probes are appropriate for interstitial measurements of radiance in tissue.
      Flat cleaved probes have the advantage of high responsivity, and they are easy to
      insert into tissue. Owing to the non-isotropic response of flat cleaved probes, a
      calibration function is required, taking the anisotropy in the radiance in tissue
      into account. STUDY DESIGN, MATERIALS AND METHODS: The method used to determine
      this function consists of radiance measurements in tissue, performed with a flat
      cleaved fiber probe mounted on a stereotactic stage for insertion into the tissue
      from different directions. Interstitial irradiation at 630 nm was delivered by a
      spherical source. RESULTS: We found that the degree of anisotropy in the radiance
      decreases with increasing distance from the interstitially implanted source in
      two different tissue phantoms and in the Dunning R3327-AT and R3327-H rat tumor
      models. CONCLUSION: A position-dependent calibration function is required for
      interstitially implanted flat cleaved fiber probes. An anisotropy function is
      presented, which modifies the measurements of radiance with a flat cleaved probe,
      to account for the change in anisotropy in the radiance. The anisotropy functions
      for the two tumor models differ substantially.

PMID- 8983010
TI  - Nd:YAG laser transurethral evaporation of the prostate (TUEP) for urinary
      retention.
AB  - BACKGROUND AND OBJECTIVE: Little information is available regarding the
      effectiveness of laser prostatectomy in patients with urinary retention from
      benign prostatic hyperplasia since there is no paper specifically dealing with
      laser prostatectomy in patients in urinary retention. STUDY DESIGN/MATERIALS AND
      METHODS: Twenty two unselected consecutive patients presenting with urinary
      retention due to benign prostatic hypertrophy underwent transurethral evaporation
      of the prostate (TUEP) using a neodymium:YAG laser and total internally
      reflecting side-firing free beam quartz fiber. All patients failed at least one
      voiding trial and averaged > 30 days of urinary catheter drainage preoperatively.
      A contact evaporation technique was used to evaporate a "TURP-like" channel in
      the prostatic fossa by means of a series of parallel evaporation troughs.
      RESULTS: Eighteen of 22 patients completed 6 months of follow up. Two patients
      were lost to follow up and two failed TUEP. The average AUA score dropped from 26
      to 9 at 1 month and to 3.4 by 6 months postoperatively. All patients who
      successfully underwent TUEP were urinating spontaneously by 10 days. Average time
      to catheter removal was 3.5 days. Maximal uroflow was 15.7 ml/sec at 1 month and
      20.3 ml/sec by 6 months. Postvoid residual preoperatively averaged 784 ml and
      decreased to 76 ml by 1 month. Pre- and postoperative hematocrit and serum sodium
      values did not vary by more than 5%. CONCLUSION: From this preliminary series we
      conclude that aggressive evaporation of prostatic tissue is feasible
      endoscopically and provides a reliable method of near bloodless removal of
      tissue.

PMID- 8983011
TI  - Tendon repair by laser welding: a histologic and biomechanical comparison and
      suture repair with CO2 and argon lasers.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to determine whether
      welding of tendinous tissue is possible with the application of thermal lasers.
      STUDY DESIGN MATERIALS AND METHODS: After sharp transection of a unilateral
      achilles tendon, 40 male outbred Spraque Dawley rats were divided equally between
      four treatment groups. Ten animals underwent repair using the modified Kessler
      suture technique. The remaining animals underwent application of laser after the
      tendon edges were reapproximated and held in place with a vascular clamp. CO2 and
      Nd:YAG lasers were applied using 25% human albumin as a solder. Fluorescein dye
      was added to albumin and used as solder for the Argon laser. Biomechanical and
      histologic testing were performed immediately and 14 days postoperatively.
      RESULTS: Argon and CO2 lasers successfully fused the tendon ends together.
      However, immediately postoperative, the resultant tissue weld was tenuous and
      conventional tensile strength testing was not possible. At 14 days
      postoperatively, all modes of tendon repair resulted in tensile failure at
      consistently lower levels of tension than those required for the normal uninjured
      tendons. The ultimate tensile strength for the suture-repaired, CO2 laser welded,
      and Argon laser welded tendons were 74%, 59%, and 64% of the strength of the
      control tendons respectively. No statistically significant difference was found
      in the tensile strength among the three repair groups. Histologic evaluation at
      14 days revealed the greatest degree of inflammatory response in those tendons
      repaired with the Argon laser. Those tendons repaired with suture demonstrated
      the least amount of inflammatory change. CONCLUSION: Our study demonstrates that
      welding of a tendon is possible with the application of laser energy. However, we
      were unable to produce a weld sufficient to withstand significant tensile loads
      in the immediate postoperative period.

PMID- 8983012
TI  - Photodynamic therapy to control life-threatening hemorrhage from hereditary
      hemorrhagic telangiectasia.
AB  - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) was used to stop life
      threatening hemoptysis from bleeding hereditary telangiectasia in bronchi in a 42
      year-old man with a 4-year history of repeated embolotherapies, tracheostomies,
      and ventilator dependence. At the time of his first PDT, he was 10 days past his
      third embolotherapy, was being ventilated through a tracheostomy and bringing up
      100-200 cc of blood daily, necessitating multiple transfusions of blood and
      platelets. STUDY DESIGN/MATERIAL AND METHODS: Four hours after intravenous
      injection (60 mg/m2 body surface) of the photosensitizer dihematoporphyrin ether
      (DHE), bronchoscopy through his tracheostomy showed continuous oozing of non
      clotting blood from bronchial vessels in both lung fields, requiring continuous
      suction. We performed PDT to seven bronchial sites. The 630 nm wavelength light
      energy to activate the photosensitizer was generated by a tunable dye argon laser
      system and delivered to the endobronchus through a quartz fiber modified with a
      2.5 cm diffusing tip passed through the biopsy channel of the bronchoscope. The
      light power was 500 mW per cm of diffuser and the light dose was 200 J per cm of
      diffuser. At the end of the treatments, the bleeding had decreased so as not to
      require suctioning. The following day we treated three other sites with the same
      light dose. At this time the only bleeding was from the LUL, which oozed briskly
      after passing the bronchoscope through it. At the end of the treatment
      bronchoscopy there was minimal bleeding. RESULTS: One week after PDT he was
      discharged with a tracheosotomy and mechanical ventilator. Four months later his
      tracheostomy was removed. He remained free of hemoptysis for 26 months when life
      threatening hemoptysis recurred. Twenty-two hours after his second injection of
      DHE, we treated four different endobronchial sites with PDT for bleeding from
      both the right and left bronchial tree. Sixteen months after his second PDT he
      remains free of hemoptysis. Three other patients treated for uncontrollable life
      threatening hemoptysis for bronchitis have remained free of hemoptysis for 9, 17,
      and 23 months. CONCLUSIONS: Photodynamic therapy causes thromobosis and can
      control bleeding from small vessels regardless of their location or etiology.

PMID- 8983013
TI  - Epithelial growth and differentiation: an overview.

PMID- 8983014
TI  - Formation of asymmetric unit membrane during urothelial differentiation.
AB  - Mammalian urothelium undergoes unique membrane specialization during terminal
      differentiation making numerous rigid-looking membrane plaques (0.3-0.5 micron
      diameter) that cover the apical cell surface. The outer leaflet of these membrane
      plaques is almost twice as thick as the inner leaflet hence the name asymmetric
      unit membrane (AUM). Ultrastructural studies established that the outer leaflet
      of AUM is composed of 16 nm particles forming two dimensional crystals, and that
      each particle forms a 'twisted ribbon' structure. We showed recently that highly
      purified bovine AUMs contain four major integral membrane proteins: uroplakins Ia
      (27 kD), Ib (28 kD), II (15 kD) and III (47 kD). Studies of the protease
      sensitivity of the different subdomains of uroplakins and other considerations
      suggest that UPIa and UPIb have 4 transmembrane domains, while UPII and UPIII
      have only one transmembrane domain. Chemical crosslinking studies showed that
      UPIa and UPIb, which share 39% amino acid sequence, are topologically adjacent to
      UPII and UPIII, respectively, thus raising the possibility that there exist two
      biochemically distinct AUM particles, i.e., those containing UPIa/UPII vs.
      UPIb/UPIII. Bovine urothelial cells grown in the presence of 3T3 feeder cells
      undergo clonal growth forming stratified colonies capable of synthesizing and
      processing all known uroplakins. Transgenic mouse studies showed that a 3.6 kb 5'
      flanking sequence of mouse uroplakin II gene can drive the expression of
      bacterial LacZ gene to express in the urothelium. Further studies on the
      biosynthesis, assembly and targeting of uroplakins will offer unique
      opportunities for better understanding the structure and function of AUM as well
      as the biology of mammalian urothelium.

PMID- 8983015
TI  - Prostate epithelial differentiation is dictated by its surrounding stroma.
AB  - Prostate epithelial differentiation is dictated by its surrounding stroma which
      determines androgen induced growth responsiveness and expression of specific
      secretory proteins in normal prostate gland. During neoplastic progression, organ
      specific stroma has been shown to determine the rate of neoplastic progression
      from androgen-dependent to androgen-independent and metastatic states. Although
      growth factors and extracellular matrix are recognized as important contributors
      to prostate epithelial growth, hormonal responsiveness, and neoplastic
      progression, the exact mechanism of intercellular communication between stromal
      and epithelial cells remains undefined. In addition to the importance of defining
      the reciprocal interaction between stromal and epithelial interaction in the
      prostate, clonal interaction between two dissimilar prostate epithelial cell is
      also recognized to contribute to disease progression. In this review, we
      summarized recent advances made in delineating molecular mechanisms underlying
      stromal epithelial interaction and clonal interaction between androgen-dependent
      and androgen-independent prostate cancer cells in vivo and in culture.
      Understanding cellular interaction between prostate epithelium and its
      surrounding stroma could help us in developing metastatic models of prostate
      carcinogenesis. This concept will allow us to define epithelial-specific markers,
      markers induced as the result of stromal-epithelial interaction, and stroma
      associated markers. These markers together will assist us in diagnosing,
      preventing, prognosing and treating prostate cancer more efficaciously in the
      future.

PMID- 8983016
TI  - Stem cell-fed maturational lineages and gradients in signals: relevance to
      differentiation of epithelia.

PMID- 8983017
TI  - Molecular complexity of the cutaneous basement membrane zone.
AB  - Ultrastructural examination of the cutaneous basement membrane zone (BMZ) reveals
      the presence of several attachment structures, which are critical for integrity
      of the stable association of epidermis and dermis. These include hemidesmosomes
      which extend from the intracellular compartment of the basal keratinocyte to the
      underlying basement membrane where they complex with anchoring filaments, thread
      like structures traversing the lamina lucida. At the lower portion of dermal
      epidermal attachment zone, anchoring fibrils extend from the lamina densa to the
      papillary dermis, where they associate with basement membrane-like structures,
      known as anchoring plaques. Molecular cloning of the cutaneous BMZ components has
      allowed elucidation of the structural features of the proteins which constitute
      these attachment structures. Specifically, hemidesmosomes have been shown to
      consist of at least four distinct proteins. The intracellular hemidesmosomal
      inner plaque is comprised of the 230-kD bullous pemphigoid antigen (BPAG1), and
      plectin, a high-molecular weight cytomatrix protein, encoded by the corresponding
      gene, PLEC1. The transmembrane component of the hemidesmosomes consists of the
      180-kD bullous pemphigoid antigen (BPAG2), a collagenous protein also known as
      type XVII collagen (COL17A1), as well as of the basal keratinocyte-specific
      integrin alpha 6 beta 4. The anchoring filaments consist predominantly of laminin
      5 with three constitutive subunit polypeptides, the alpha 3, beta 3 and gamma 2
      chains, which is associated with laminin 6 with the chain composition alpha 3,
      beta 1 and gamma 1. Also associated with anchoring filaments is a novel protein,
      ladinin, which serves as autoantigen in the linear IgA disease, and the
      corresponding gene, LAD1, has been mapped to human chromosome 1. Finally, the
      major, if not the exclusive, component of anchoring fibrils is type VII collagen,
      encoded by the gene (COL7A1) which consists of 118 distinct exons, the largest
      number of exons in any gene published thus far. Collectively, the cutaneous
      basement membrane zone is a complex continuum of macromolecules which form a
      network providing the stable association of the epidermis to the underlying
      dermis. Thus, genetic lesions resulting in abnormalities in any part of this
      network could result in a blistering skin disease, such as epidermolysis bullosa.

PMID- 8983018
TI  - Regulation and clinical implications of corneal epithelial stem cells.
AB  - The corneal epithelium is known to have a rapid self-renewing capacity. The major
      advance in the field of corneal epithelial cell biology in the last decade is the
      establishment of the location of corneal epithelial stem cells at the limbus,
      i.e., the junctional zone between the cornea and the conjunctiva. This concept
      has helped explain several experimental and clinical paradoxes, produced a number
      of important clinical applications, and spawned many other research studies. This
      unique enrichment of epithelial stem cells at a site anatomically separated from
      their transient amplifying cells makes the ocular surface an ideal model to study
      the regulation of epithelial stem cells. The present review includes data from
      more recent studies and lays out other areas for future investigation, especially
      with respect to the role of apoptosis and cytokine dialogue between limbal
      epithelial stem cells and their stromal microenvironment.

PMID- 8983020
TI  - Identification of novel homologues of three low molecular weight subunits of the
      mitochondrial bc1 complex.
AB  - Large-scale random cDNA sequencing projects have been started for several
      organisms and are a valuable tool for the analysis of quantitative and
      qualitative aspects of gene expression. However, the reliability of the obtained
      data is limited as most of the clones are only partially analysed on one strand.
      As a consequence the sequence entries derived from random cDNA sequencing
      projects usually comprise incomplete open reading frames. They nevertheless
      define complete and reliable coding sequences, if two prerequisites are
      fulfilled: (i) the clones encode very small proteins, and (ii) the clones have a
      high frequency in the cDNA-banks. The present study describes the use of cDNA
      databases for the identification of homologues of three low-molecular-weight
      subunits of the mitochondrial bc1 complex, termed the QCR6, QCR9 and QCR10
      proteins. These polypeptides are only characterized for a small number of
      organisms, have a scarcely defined function and exhibit a low degree of
      structural conservation if compared between different species. Several clones
      were identified for each polypeptide by searches with TBLASTN using the known
      sequences as probes. Most of the database entries contain complete open reading
      frames and sequencing queries could be excluded due to the abundancy of the
      clones. Multiple sequence alignments are presented for all three polypeptides and
      consensus sequences are given which may provide a basis for the investigation of
      the proteins by site-directed mutagenesis.

PMID- 8983021
TI  - Structural and functional homology between the 29 kD rat liver nucleoprotein and
      the high mobility group 1 protein.
AB  - A 29 kD soluble rat liver nucleoprotein (p29) has increased binding affinity for
      the hormone responsive element (RE) of the rat haptoglobin (Hp) gene during the
      acute-phase reaction. In this work the possibility of its structural and
      functional homology to the high mobility group 1 (HMG1) nonhistone protein
      constituent of chromatin was examined. The results of two-dimensional gel
      electrophoresis, Southwestern and Western immunoblot analyses, showed that p29
      and HMG1 are homologous protein species. On the basis of in vitro and in vivo
      phosphorylation/dephosphorylation experiments, we discuss the modulatory role of
      phosphate groups in view of the structure and function of p29.

PMID- 8983022
TI  - Production of recombinant proteins in Chinese hamster ovary cells overexpressing
      the subtilisin-like proprotein converting enzyme furin.
AB  - The proprotein processing enzyme furin is the mammalian prototype of a novel
      family of subtilisin-like serine endoproteases which possess cleavage specificity
      for sites involving multiple basic amino acid residues and are involved in the
      processing of precursor proteins of a variety of regulatory peptides and
      proteins. One of the limiting steps in the engineering of mammalian cells
      designed for the overproduction of secreted proteins is the endoproteolytic
      cleavage of the precursor molecule to its mature biologically active form. The
      extremely low level of endogenous furin is likely the reason why cells are not
      able to fully mature overexpressed precursor proteins to their mature form. Here,
      we report a CHO-derived cell line genetically engineered for the production of
      high levels of recombinant proteins that need such endoproteolytic maturation.
      First, the human furin cDNA under the control of the cytomegalovirus early
      promoter and enhancer was introduced and overexpressed in a DHFR-deficient CHO
      cell line. A permanent cell line CHO-D3-FUR was established that expressed
      biologically active furin. Subsequently, to demonstrate the capacity of CHO-D3
      FUR cells to produce recombinant proteins in a fully matured form, two derivative
      cell lines were established that overexpressed the von Willebrand factor (vWF)
      and transforming growth factor beta 1 (TGF beta 1); CHO-D3-vWF and CHO-D3-TGF
      beta 1, respectively. Both derivative cell lines were able to produce relatively
      high levels of recombinant protein in a fully matured and biologically active
      form. Our results illustrate the potential of the CHO-D3-FUR cell line in the
      production of recombinant secretory proteins that need endoproteolytic activation
      at the consensus furin cleavage sequence Arg-X-Lys/Arg-Arg.

PMID- 8983019
TI  - Transcription factor regulation of epidermal keratinocyte gene expression.
AB  - The epidermis is a tissue that undergoes a very complex and tightly controlled
      differentiation program. The elaboration of this program is generally flawless,
      resulting in the production of an effective protective barrier for the organism.
      Many of the genes expressed during keratinocyte differentiation are expressed in
      a coordinate manner; this suggests that common regulatory models may emerge. The
      simplest model envisions a 'common regulatory element' that is possessed by all
      genes that are regulated together (e.g., involucrin and transglutaminase type 1).
      Studies to date, however, have not identified any such elements and, if anything,
      the available studies suggest that appropriate expression of each gene is
      achieved using sometime subtly and sometime grossly different mechanisms. Recent
      studies indicate that a variety of transcription factors (AP1, AP2, POU domain.
      Sp1, STAT factors) are expressed in the epidermis and, in many cases, multiple
      members of several families are present (e.g., AP1 and POU domain factors). The
      simultaneous expression of multiple members of a single transcription factor
      family provides numerous opportunities for complex regulation. Some studies
      suggest that specific members of these families interact with specific
      keratinocyte genes. The best studied of these families in epidermis is the AP1
      family of factors. All of the known AP1 factors are expressed in epidermis [52]
      and each is expressed in a specific spatial pattern that suggests the potential
      to regulate multiple genes. It will be important to determine the role of each of
      these members in regulating keratinocyte gene expression. Finally, information is
      beginning to emerge regarding signal transduction in keratinocytes. Some of the
      early events in signal transduction have been identified (e.g., PLC and PKC
      activation, etc.) and some of the molecular targets of these pathways (e.g., AP1
      transcription factors) are beginning to be identified. Eventually we can expect
      to elucidation of all of the steps between the interaction of the stimulating
      agent with its receptor and the activation of target gene expression.

PMID- 8983024
TI  - Positive and negative modulation of H-ras transforming potential by mutations of
      phenylalanine-28.
AB  - Conserved amino-acids of H-ras from residues 25 to 34 were mutated in human H-ras
      cDNA with a pre-existing valine-12 activating mutation ([V12]p21), and built into
      SV40-driven expression vectors. The influence of the introduced mutations was
      initially screened by transfection of Rat-1 cells to score foci of transformed
      cells. Non-conservative mutations of amino-acids 25 (tryptophan for glutamine),
      27 (asparagine for histidine) and 34 (alanine for proline) did not abrogate the
      transforming potential of [V12]p21. The conservative mutation of phenylalanine-28
      to tryptophan ([V12W28]p21) was also still transforming. Significantly, in the
      absence of the valine-12 activating mutation, tryptophan-28-ras ([W28]p21) was
      weakly transforming while, in contrast, [V12D28]p21 was unable to transform Rat-1
      cells and retarded cell growth. Analysis of the binding and dissociation of GTP
      and GDP to normal and mutated p21 expressed in Escherichia coli showed that
      [V12D28]p21 and [D28]p21 do not bind GTP. The dissociation rate of both GTP and
      GDP bound to [W28]p21 is increased, suggesting a mechanism for its transforming
      potential in Rat-1 cells. These studies illustrate the importance of
      phenylalanine-28 in guanine nucleotide binding by p21H-ras. The mutations
      described could be valuable tools in investigations of cellular signal
      transduction involving small GTP-binding proteins.

PMID- 8983023
TI  - Functional analysis of the promoter and first intron of the human lysyl oxidase
      gene.
AB  - Alterations in the synthesis and activity of lysyl oxidase occur concomitant with
      developmental changes in collagen and elastin deposition and with the
      pathogenesis of several acquired and heritable connective tissue disorders. To
      begin to unravel the mechanisms that control lysyloxidase gene expression, we
      have previously reported the complete exon-intron structure of the human lysyl
      oxidase gene. We have now sequenced this entire gene, including all six introns
      and 4 kb of DNA 5' of exon 1. Analysis of over 13 kb of intervening sequence and
      5' flanking sequence revealed a concentration of conserved consensus sequence
      elements within the first intron and 1 kb immediately 5' of exon 1. Analysis of
      intron 1 and the 5' flanking domain, using recombinant plasmids containing the
      chloramphenicol acetyl transferase (CAT) reporter gene, identified functional DNA
      sequence elements within these non-coding domains responsible for inhibition and
      up-regulation of CAT activity in primary cultures of human skin fibroblasts, in
      smooth muscle cells, revertant cells derived from an osteosarcoma cell line and
      malignant c-Ha-ras-transformed osteosarcoma cells. DNA sequence elements within
      intron 1, in particular, resulted in a marked increase in CAT reporter activity
      in cultured fibroblasts, smooth muscle cells and osteosarcoma cells. In c-Ha-ras
      transformed osteosarcoma cells, however, no such enhancer activity of intron 1
      sequence was observed. Ras-transformed osteosarcoma cells exhibited reduced
      steady-state levels of lysyl oxidase mRNA that was primarily controlled through
      reduced transcription of the lysyl oxidase gene. The lack of any up-regulation of
      CAT activity in these ras-transformed cells by sequence elements within intron 1
      suggests a complex interaction between cis-acting domains and trans-acting
      transcriptional factors in the 5' promoter domain and the first intron of the
      lysyl oxidase gene.

PMID- 8983025
TI  - Rosetteness in Portulaca grandiflora: an altered genetic expression.
AB  - Rosetteness is either developmentally controlled or induced by various biotic and
      abiotic stresses. Prolonged vegetative growth and/or pruning seems to be inducing
      rosetteness in Portulaca grandiflora. Analysis of cellular extracts from rosette
      stems by SDS-PAGE, revealed induction of a polypeptide of high molecular mass
      (approximately equal to 58 kDa) and over-expression of a few lower molecular
      weight polypeptides. However, leaves showed no differences in the protein
      profiles.

PMID- 8983026
TI  - Methylation status of Sillago japonica satellite DNA examined by bisulfite
      modification.
AB  - A member of Sillago japonica satellite DNA contained internal subrepeats in its
      174 bp unit. S. Japonica genomic DNA isolated from liver tissue was subjected to
      bisulfite modification, and the DNA sequences of about 40 bp flanked by both
      subrepeats were amplified by polymerase chain reaction (PCR). This protocol,
      combination of bisulfite reaction and PCR, converts cytosines in the genomic DNA
      to thymines in the amplified DNA, whereas 5-methylcytosines in the genomic DNA
      remain as cytosines. Sequence analysis of the amplified DNA fragments revealed
      that most of the cytosine residues at CpG were methylated in this region.

PMID- 8983027
TI  - Frequency of hippocampal formation atrophy in normal aging and Alzheimer's
      disease.
AB  - We used CT and MR to examine the frequency of occurrence of hippocampal formation
      atrophy (HA) in a research clinic population of 130 normal elderly, 72
      nondemented patients with very mild memory and cognitive impairments (MCI), 73
      mild Alzheimer's disease (AD) patients, and 130 patients with moderate to severe
      AD. HA was found in 29% of the normal elderly group and its frequency of
      occurrence was strongly related to increasing age. For normal elderly 60-75 years
      of age, 15% had HA: the proportion rose to 48% in subjects 76-90 years of age.
      Among the three groups of impaired patients, the frequencies of HA ranged from
      78% in the MCI patients to 96% in the advanced AD group. Unlike the normal
      elderly group, the percentages were not related to age. In both the normal
      elderly group and MCI group disproportionately more males than females had HA.
      After controlling for learning and the effects of generalized brain changes as
      reflected in ventricular size, only in the normal group was HA associated with
      reduced delayed verbal recall performance. Follow-up examinations for 15
      individuals with baseline HA. 4 who at entry were MCI and 11 probable AD, yielded
      clinical and neuropathologic diagnoses of AD in all cases. The results of the
      present study indicate that hippocampal formation atrophy is associated with
      memory and cognitive impairments. Further longitudinal and neuropathologic work
      is required to validate the relationship between hippocampal formation atrophy
      and AD.

PMID- 8983028
TI  - Recognition memory span in rhesus monkeys of advanced age.
AB  - Assessment of recognition memory was performed on eight rhesus monkeys of
      advanced age (25 to 27 years of age) using the delayed recognition span test
      (DRST). Their performance was compared to that of five young adult animals (5 to
      7 years of age) on two stimulus conditions of the DRST: spatial position and
      color. Both trial unique and repeating series were used for each of the two
      conditions. As a group, aged monkeys were impaired on both the spatial and color
      conditions of the DRST, achieving about two-thirds of the span of the young adult
      group in each condition. Error analyses revealed that monkeys in the aged group
      also produced more perseverative responses (i.e., displacing the previously
      correct disk) than did young adults. Together the findings suggest that monkeys
      of advanced age are impaired on tasks with memory loading demand characteristics.

PMID- 8983029
TI  - The effects of 5-HT3 receptor antagonists on cognitive performance in aged
      monkeys.
AB  - The serotonin 5-HT3 receptor antagonists ondansetron and SEC-579 were tested over
      a wide dose range (0.000001-0.5 mg/kg, PO) for cognitive-enhancing effects in
      aged rhesus monkeys. Animals were tested on the following cognitive and motor
      tasks: 1) acquisition of a visual object discrimination; 2) reversal of a visual
      object discrimination; 3) the delayed response task, a spatial working memory
      task; and 4) a fine motor task. This study found enhanced acquisition of a visual
      object discrimination following very low doses (0.000001-0.00001 mg/kg, PO) of
      either 5-HT3 receptor antagonist. This finding replicates a previous study in
      marmosets. However, unlike the marmoset research, no reliable improvement was
      found on the reversal condition. Similarly, no improvement was observed on the
      delayed response or fine motor tasks. No side effects were observed at any dose,
      consistent with reports in both animals and humans. These results suggest that 5
      HT3 receptor antagonists may be helpful in treating a subset of cognitive
      functions.

PMID- 8983030
TI  - A further evaluation of the effect of age on striate cortex of the rhesus monkey.
AB  - The brains of 14 rhesus monkeys (Macaca mulatta) between 4 and 35 years old were
      examined to determine the effects of aging on the thickness, neuronal frequency,
      fine structure, surface area, and volume of striate cortex. The effects of aging
      were ascertained by comparing the striate cortex in the six monkeys between 4 and
      12 years of age with that of the eight monkeys over 25 years of age. The brains
      of the monkeys were all fixed by vascular perfusion and except for one of the old
      monkeys, whose age was estimated, the exact ages of all of the monkeys are known.
      One micron thick sections of plastic embedded cortex from one hemisphere of each
      monkey were examined by light microscopy to determine the thickness of the
      striate cortex, and neuronal frequency was determined by counting the numbers of
      neurons displaying nuclei in 250 microns-wide strips passing through the
      thickness of the cortex. When young monkeys were compared with the old ones, no
      differences were found in either the thickness of the cortex or in the numbers of
      neuronal profiles beneath unit areas of cortical surface. This suggests that
      neurons are not lost with age, and when the cortices were examined by electron
      microscopy there was no indication that the cell bodies of neurons are
      degenerating, except possibly in layer 1. Serial, 30 microns-thick, Nissl stained
      frozen sections from the other hemisphere of each monkey were used to determine
      both the surface area and the volume of the striate cortex. Overall, the surface
      area varied between 702 and 1480 mm2, with a mean value of 956 mm2, but there was
      no indication that the surface area decreased with age, and the same is true for
      the volume of striate cortex. The conclusion is that while there is a large
      variation in the amount of cortex occupied by area 17, there is no indication
      that its thickness, volume, or number of neurons is altered by age.

PMID- 8983031
TI  - Effect of aging on the basal expression of c-Fos, c-Jun, and Egr-1 proteins in
      the hippocampus.
AB  - In the present study the effect of aging on the basal expression of three
      different immediate early genes (IEGs) was investigated. The protein products of
      c-fos, c-jun, and egr-1 genes were visualized immunohistochemically in the rat
      hippocampus of young adult (4-month-old) and old rats (20-month-old). Astrocytes
      were quantified by GFAp immunostaining to determine whether changes in the
      expression of IEGs were correlated with modifications in this marker of
      degenerative changes. In the young adult rat brain, basal levels of c-Jun and Egr
      1 but not c-Fos were detected within the hippocampal formation. Whereas very high
      basal levels of c-Jun were found in the dentate granule cells and in the
      pyramidal cells of the ventral hippocampus, Egr-1 was highly expressed in the CA1
      pyramidal cells of the dorsal hippocampus. Aging was accompanied by a decrease in
      Egr-1 expression, by a decrease in total cell density, as well as by a loss of
      astrocytes in CA1 subfields. In contrast, basal expression of c-Fos and c-Jun as
      well as astrocyte density within the dentate gyrus were not affected by aging. No
      difference in these markers was observed in aged rats with or without impairment
      in spatial learning in a water maze. It was concluded that although these changes
      may reflect senescence-induced decline of brain function, they do not constitute
      the defect underlying the age-associated reduction in mnesic capability.

PMID- 8983032
TI  - Age-related changes in c-fos mRNA induction after open-field exposure in the rat
      brain.
AB  - In the present study, functional activation of brain regions was measured by the
      induction of c-fos and c-jun mRNA following exposure to a novel open field.
      Fischer 344 rats at 5 months, 14 months, and 21 months were exposed to a square
      open field for 20 min. Rats were then immediately sacrificed and their brains
      were examined for c-fos and c-jun mRNA using in situ hybridization. Control rats
      were sacrificed directly from their home cage. Results showed no significant age
      related changes in locomotor activity. Autoradiogram analyses showed that open
      field exposure induced c-fos mRNA throughout the brain, while c-jun mRNA was
      induced in a few brain regions. Aged rats showed a lower elevation of c-fos mRNA
      in the prelimbic cortex compared to 5-month rats. In addition, grain analyses
      revealed age-related decreases in c-fos mRNA induction in the medial prefrontal
      cortex, caudate, and ventral lateral septum. These findings indicate age-related
      changes in the induction of c-fos mRNA in certain brain regions following
      exploration of a novel environment.

PMID- 8983033
TI  - Dopaminergic function in the neostriatum and nucleus accumbens of young and aged
      Fischer 344 rats.
AB  - Age-dependent alterations in behavioral and neuronal functioning were assessed in
      young (2-3 month), middle-aged (12 month), and aged (24 month) Fischer 344 rats
      treated with the indirect dopamine agonist amphetamine (2.25 or 5 mg/kg), the D1
      agonist SKF 38393 (7.5, 15, 30 mg/kg), or the D2 agonist quinpirole (0.3, 1.0,
      3.0 mg/kg). Drug-induced changes in activity and stereotypy were measured during
      a 90-min testing session, with Fos immunohistochemistry being used to assess the
      neuronal response to dopamine agonist treatment. As expected, aged rats given
      amphetamine (5 mg/kg) had fewer activity counts and higher stereotypy scores than
      young rats. Middle-aged rats also had fewer activity counts but were similar in
      stereotypy scores to young rats. Amphetamine also induced different patterns of
      Fos immunoreactivity in the neostriatum and nucleus accumbens of young and aged
      rats, as Fos expression in aged rats exhibited a distinctive dorsal to ventral
      pattern of decline. In general, SKF 38393 had few age-related actions, although
      aged rats did show a slight relative increase in stereotypy. In contrast, the D2
      agonist quinpirole substantially enhanced the motor activity and Fos expression
      of young rats, while only modestly affecting aged rats. Hence, these results
      suggest that the D2 receptor is more vulnerable to the effects of aging than the
      D1 receptor.

PMID- 8983035
TI  - Differential susceptibility of senile and lesion-induced astrogliosis to
      phosphatidylserine.
AB  - The susceptibility of age- and lesion-induced astrogliosis to the treatment with
      phosphatidylserine was investigated with the use of GFAP immunoblotting. The
      existence of age-induced upregulation of GFAP content was confirmed in the
      hippocampus, septum, and corpus callosum of the rat. The Ptd-Ser treatment of the
      aged rats further increased the GFAP content in the hippocampus and corpus
      callosum. The GFAP content increase in the corpus callosum was additionally
      illustrated by the upregulation in GFAP immunostaining. In the septum no further
      elevation of GFAP was observed after Ptd-Ser treatment, and in the striatum the
      compound elicited significant GFAP content increase, absent in the untreated aged
      rat brain striatum. In the intact adult rat brain no effect of Ptd-Ser on GFAP
      content was observed; neither did the compound elicit any modulation of the
      astrogliosis related to the mechanical lesion of the brain in the septum,
      hippocampus, cortex, and striatum. In the corpus callosum, Ptd-Ser potentiated
      the GFAP content increase related to the mechanical lesion, pointing to the
      structure-related heterogeneity of astrocytic population. Because it has been
      previously found that Ptd-Ser partly reverses one of the aspects of rodent brain
      aging, the aging-induced decrease of the acetylcholine release, the possibility
      exists that the effects of Ptd-Ser administration on glia and neurons in the aged
      brain may be related.

PMID- 8983034
TI  - Neurotrophin receptor and tyrosine hydroxylase gene expression in aged
      sympathetic neurons.
AB  - Ribonuclease protection measurements revealed decreases of 26% in p75
      neurotrophin receptor mRNA and 30% in trkA mRNA in superior cervical ganglia
      (SCG) of aged Long-Evans rats. These declines were not related to the presence of
      a spatial memory impairment, whose presence is known to strongly predict
      increased hypothalamic-pituitary-adrenal axis activity in these aged animals. A
      similar decrease with age was observed in p75, but not cyclophilin mRNA levels in
      SCG from F-344 inbred rats. In situ hybridization with paired sections from
      mature and aged F-344 rats revealed a 25% decline in the mean neuronal labeling
      index (LI) for p75 mRNA. In other paired sections, mean trkA LI decreased 16%,
      tyrosine hydroxylase (TH) LI increased 74% and cyclophilin LI did not change.
      Neuronal hypertrophy, p75 decreases and TH increases all occurred to a greatest
      extent in intermediate-sized neurons, resembling those innervating the pineal and
      cerebral vessels. In contrast to other SCG targets, this innervation is known to
      decline nearly 50% with aging. Retrograde tracer/in situ hybridization studies
      will be required to establish whether decreased p75 represents a marker for
      selective axonal regression and also to determine the significance of increased
      TH and neuronal hypertrophy.

PMID- 8983036
TI  - Age-related prefrontal alterations during auditory memory.
AB  - Event-related potentials were recorded from young and elderly subjects while they
      performed a modified auditory Sternberg memory task. Aging was associated with a
      decrease in frontal activation, suggesting that prefrontal alterations may be
      central to age-related impairments in auditory working memory. Young subjects
      showed significant serial position effects electrophysiologically, while elderly
      subjects showed no recency effects for P3 latency and no serial position effects
      for N4 and SFN amplitude. This finding, in combination with increased false alarm
      rates in the elderly, suggest that the two group of subjects employed different
      cortico-limbic circuits to perform the task.

PMID- 8983037
TI  - Lymphocyte content of amyloid precursor protein is increased in Down's syndrome
      and aging.
AB  - We quantified cellular amyloid precursor protein (APP) in ethanol-permeabilized
      peripheral lymphocytes from 13 subjects with Alzheimer's disease (AD), 11
      subjects with Down's syndrome (DS), and 13 healthy elderly and 31 healthy young
      controls. APP content was analyzed by indirect immunofluorescence and flow
      cytometry, using the 22C11 monoclonal antibody (mAb) directed against an N
      terminal domain of APP. Authenticity of 22C11 APP signal was confirmed by
      immunoblotting and flow cytometry studies with the mAb 6E10, directed against the
      A beta domain of APP. Consistent with gene dosage, patients with DS had 1.51-fold
      higher lymphocyte APP signal than age-matched normal young subjects (corrected p
      < 0.05). Both AD patients and elderly control groups had significantly increased
      lymphocyte APP signal compared to young controls (either comparison corrected p <
      0.01). Indeed, increasing age in non-DS subjects was significantly correlated
      with lymphocyte APP (r = 0.508, p < 0.0001), such that APP immunoreactivity more
      than doubled from 20 to 80 years. Lymphocyte APP was nonsignificantly higher in
      AD vs. aged controls in this small sample. Increased cellular APP content in DS
      and aging may correspond to generalized alterations in expression or processing
      of this molecule, and suggests a novel determinant for the timing of AD onset.

PMID- 8983038
TI  - Different manifestations of circadian rhythms in senile dementia of Alzheimer's
      type and multi-infarct dementia.
AB  - Using an actigraph and a long-term body temperature (BT) monitoring system, we
      simultaneously monitored rest-activity (R-A) and BT rhythms in patients with
      senile dementia of Alzheimer's type (SDAT; n = 20) or multi-infarct dementia
      (MID; n = 21) for 5-7 consecutive days. The SDAT group exhibited a well-organized
      BT rhythm with significantly higher amplitude compared with the MID group. The
      SDAT group also showed significant positive correlation between the total daily
      activity as well as percentage of nighttime activity and the degree of dementia,
      while no such tendency was observed in the MID group. The different properties of
      the biological rhythm disorders among the SDAT and MID groups possibly underlie
      their sleep and behavioral disorders.

PMID- 8983039
TI  - Cholinergic activation of phosphoinositide signaling is impaired in Alzheimer's
      disease brain.
AB  - The function of the phosphoinositide signal transduction system was compared in
      membranes from Alzheimer's disease (AD) and control postmortem brain.
      [3H]Phosphatidylinositol hydrolysis was concentration-dependently stimulated by
      GTP[S] and this was 40% lower than controls in AD prefrontal cortical membranes.
      Carbachol induced a response greater than that of GTP[S] alone, and this response
      was impaired in AD by 45%. Differential analysis of the receptor-coupled and G
      protein contributions to the responses indicated that the G-protein deficit in AD
      had a predominant influence on the lowered responses to cholinergic agonists.
      Similar deficits were observed in AD in the responses to five additional
      cholinergic agonists, including acetylcholine with three different
      acetylcholinesterase inhibitors. Deficits in stimulated phosphoinositide
      hydrolysis were regionally selective and these deficits did not correlate
      directly with reductions in choline acetyltransferase activity in AD tissues.
      These data demonstrate that in AD there is a brain region-selective, large
      impairment of cholinergic agonist-induced signal transduction mediated by the
      phosphoinositide system, which we speculate may impact on amyloid precursor
      protein processing.

PMID- 8983042
TI  - Perturbation study of shading in pictures.
AB  - Pictorial relief was measured for a series of pictures of a smooth solid object.
      The scene was geometrically identical for all pictures, but the rendering was
      different. Whereas all pictures were monochrome full-scale photographs, they were
      taken under different illuminations of the scene, the source being frontal and
      displaced towards either the upper left, the upper right, the lower right, or the
      lower left. It was found that different illuminations led to significantly
      different, systematic alterations of pictorial relief. It is concluded that
      though shape constancy under changes in illumination might be said to rule in the
      first rough approximation, the deviations from true constancy are indeed both
      significant and systematic. Different from either stimulus-reduction or cue
      conflict paradigms, this 'perturbation analysis' shows that shading is used as an
      important source of information even if the particular illumination appears to be
      ignored at first blush. For all subjects, brighter parts in the stimulus were
      consistently interpreted as being nearer in pictorial space, both for the global
      layout and for the subsidiary relief.

PMID- 8983040
TI  - Apolipoprotein E genotype and amyloid load in Alzheimer disease and control
      brains.
AB  - We investigated the effect of apolipoprotein E (apoE) genotype on amyloid load in
      the frontal and cerebellar cortices of 24 patients with definite Alzheimer
      disease (AD) and 19 controls. Amyloid load was examined by using two methods: 1)
      acid-extractable amyloid beta-protein (A beta) and insoluble A beta levels of
      frontal and cerebellar cortices were measured by using enzyme-linked
      immunosorbent assay, and 2) all types of amyloid plaques and neurofibrillary
      tangles (NFT) in the frontal cortices were counted after silver staining. Acid
      extractable A beta and insoluble A beta levels were higher in AD brains than
      controls, although there was an overlap between the groups. Acid-extractable A
      beta and insoluble A beta levels were higher from AD and controls with the apoE
      epsilon 4 alleles than those without such alleles. However, the differences did
      not reach statistical significance in AD group. There was no correlation between
      acid-extractable A beta or insoluble A3 levels and the number of amyloid plaques
      in AD and control brains. However, insoluble A beta levels correlated positively
      with the number of NFT in AD brains. Our results show that although apoE epsilon
      4 influences the accumulation of A beta, multiple processes may be involved in
      deposition of A beta in the brain.

PMID- 8983043
TI  - Visual inspection of three-dimensional objects by human observers.
AB  - Eye movements are an important aid in active visual exploration of the
      environment and in performing behavioural tasks. Eye movements might also play a
      role in human perception of three-dimensional (3-D) objects. Eye-movement
      strategies were investigated when humans inspected and memorised 3-D objects.
      Subjects were instructed to memorise the 3-D structure of parts of statues of
      human figures placed on a turntable free to rotate through 360 degrees. Eye
      movements and turning behaviour were recorded. Different turning and eye-movement
      strategies could be observed. Subjects showed individual turning behaviours that
      were reproducible between trials. Turning strategies ranged from focusing on only
      a limited number of perspective views to almost continuously rotating the object
      with only short stops. On average twelve-thirteen views were inspected during
      memorising. Eye movements also revealed individual strategies. Fixation locations
      within each inspection view ranged from either closely spaced on isolated parts
      of the object to distributed over the whole view with large saccades in between.
      Eye movements were often directed to the same details from different
      perspectives. The differences in turning and viewing strategy also resulted in
      differences in the ability to recognise parts of the object later on. In general,
      successful later recognition required that the subject actually fixated the part
      to be recognised. A strategy of thoroughly inspecting the object with a series of
      closely spaced fixations from only a limited number of viewpoints led to best
      recognition rates. This was especially true for two subjects trained in fine arts
      with prior experiences in modelling. The results support models of viewpoint
      dependent object recognition with viewer-centred, two-dimensional representations
      of 3-D objects.

PMID- 8983044
TI  - Perceptual learning of stereoacuity.
AB  - It has often been noted that with repeated exposure to random-dot stereograms the
      time required to perceived depth decreases. Further, with extensive practice,
      stereoacuity thresholds have been shown to decrease. For both types of learning
      some researchers have reported specificity of the improvements to retinal
      location, and have thus suggested that the learning may be localised at early
      levels of visual processing, such as in primary visual cortex. However, these
      studies have not adequately ruled out the possibility that the specificity shown
      may be due to the operation of selective-spatial-attention mechanisms. In the
      present study this possibility was examined by training observers to judge the
      relative depth of a pair of stereograms presented equally often in two spatial
      locations, but stimuli were only presented with one direction of disparity (ie
      crossed or uncrossed) in any one location. Results indicated that, as expected,
      observers' judgements improved with practice. However, this improvement
      transferred completely to stimuli presented with the other direction of disparity
      in each location. Thus, it is argued that previous findings of retinal-location
      specific improvements in stereoacuity may well be due to selective-spatial
      attention mechanisms, rather than to learning localised at an early level of
      visual processing.

PMID- 8983045
TI  - Patterns that impair discrimination of line orientation in human vision.
AB  - The threshold for detecting a change in orientation away from the vertical of a
      briefly presented foveal line target is raised when there are immediately
      following visual presentations. This masking effect was examined by measuring the
      capacity of a variety of patterns to act as masks. When patterns were made of
      exactly the same number of light pixels, masking was least when they formed
      random dots and progressively became stronger as they formed lines of decreasing
      curvature from full circles to straight lines. The longer the lines, the stronger
      the masking. Threshold elevation was highest when the masking pattern was
      spatially superimposed on the line and was lessened when a large surround area
      was included, but there was still considerable masking when the interfering
      patterns were confined to the surround. By placing masks and test lines in
      different eyes, or by giving them opposite contrast polarity, almost complete
      interocular and interpolarity transfer was demonstrated. Relating these results
      to anatomical and electrophysiological findings about neurons in the primary
      visual cortex leads to the conclusion that the masking effects could have their
      substrates in interaction between cells in VI.

PMID- 8983046
TI  - Re-evaluation of local adaptation for motion aftereffect.
AB  - A motion aftereffect (MAE) can be induced by stimuli moving in surrounding areas.
      This suggests the relevance of mechanisms for relative motion, rather than early
      level motion detectors, which are considered to work locally. Experiments are
      reported in which the role of local adaptation in the MAE with a stimulus
      configuration comprising relative motion has been discussed. Sinusoidal gratings
      were presented in three rectangular windows: a centre window, and two windows one
      above and one below the central one. The surrounding top and bottom windows,
      which were divided into left and right halves, had gratings presented in only one
      of the two halves. The MAE duration was measured after adaptation to motion
      either in the central or in the surrounding windows, by controlling the regions
      with the gratings. From this, the regions of surrounding gratings were found not
      to have a significant effect with adaptation in the centre window. With
      adaptation in the surrounds, however, these regions did affect the MAE; the MAE
      duration was reduced when the adapted region had no gratings in the test phase.
      Thus, for an MAE it is necessary for the adapted area to be covered with stimuli
      in the test phase, which indicates the dominance of local adaptation for the MAE
      even when relative motion is relevant in producing the MAE.

PMID- 8983047
TI  - Synaesthesia: prevalence and familiality.
AB  - Synaesthesia is a condition in which a mixing of the senses occurs; for example,
      sounds trigger the experience of colour. Previous reports suggest this may be
      familial, but no systematic studies exist. In addition, there are no reliable
      prevalence or sex-ratio figures for the condition, which is essential for
      establishing if the reported sex ratio (female bias) is reliable, and if this
      implicates a sex-linked genetic mechanism. Two independent population studies
      were conducted in the city of Cambridge, England (studies 1 and 2 here), as
      necessary background to the family genetic study of synaesthesia (study 3).
      Studies 1 and 2 arrived at an almost identical prevalence rate for synaesthesia:
      approximately 1 case in 2000. The sex ratio found was 6:1 (female:male). A third
      of cases also reported familial aggregation. In study 3 six families were
      examined, and first-degree relatives were tested for genuineness of the
      condition. All six families were indeed multiplex for synaesthesia. Alternative
      modes of inheritance are discussed.

PMID- 8983048
TI  - The information that drivers use: is it indeed 90% visual?
AB  - The literature contains numerous claims that 90% of all the information used in
      driving is visual. This article presents a theoretical discussion, a citation
      search, and a review of evidence concerning such claims. The findings indicate
      that not only do we lack data from which to derive an accurate numerical
      estimate, but we lack a measurement system within which any numerical estimate
      would be meaningful. Consequently, although the information relevant to driving
      is likely to be predominantly visual, any claims about the precise percentage
      attributable to vision are premature. The proliferation of such claims in the
      absence of direct evidence is a reminder that researchers should be careful about
      assuring the validity of the claims they are passing on.

PMID- 8983049
TI  - It takes a confounded face to pop out of a crowd.
AB  - It is widely reported that a picture of an angry face seems to figuratively pop
      out of an array of happy faces, although all of these reports are based on a
      single experiment by Hansen and Hansen. Pop out, when it occurs, indicates that
      an observer has located the target by means of a preattentive, parallel search.
      Hansen and Hansen concluded that it was the affect displayed by the face which
      caused it to pop out from its surrounding distracters. However, Hansen and
      Hansen's angry faces contained extraneous dark areas which were introduced when
      they transformed Ekman and Friesen's photographs of angry and happy faces into
      black-on-white sketches. When the original artifact-free gray-scaled versions of
      angry and happy faces were used no evidence for pop out was found. All target
      faces were found during a serial, self-terminating search regardless of their
      expression. The angry face in Hansen and Hansen's experiments may have popped out
      from a crowd of happy faces because of a contrast artifact inadvertently
      introduced when they created their stimuli.

PMID- 8983050
TI  - Pigeons do not complete partly occluded figures.
AB  - One of the most common obstacles to object perception is the fact that objects
      often occlude parts of themselves and parts of other objects. Perceptual
      completion has been studied extensively in humans, and researchers have shown
      that humans do complete partly occluded objects. In an effort to understand more
      about the mechanisms underlying completion, recent research has extended the
      study of perceptual completion to other mammalian species. Monkeys and mice also
      seem to complete two-dimensional representations of partly occluded objects. The
      present study addresses the question of whether this capacity generalizes to a
      nonmammalian species, the pigeon (Columba livia). The results point to a limit of
      the generalizability of perceptual completion: pigeons do not complete partly
      occluded figures.

PMID- 8983051
TI  - Horses are sensitive to pictorial depth cues.
AB  - In an attempt to demonstrate whether horses could make use of pictorial cues to
      depth, two were trained initially to make a relative-line-length discrimination
      between two lines placed one above the other. Psychophysical measurement of their
      discrimination thresholds showed that from a viewing distance of approximately
      160 cm they could reliably distinguish a lower line of 10 cm from an upper one of
      14 cm. In the second phase of the experiment, two lines of equal length were
      superimposed on a photograph of a set of railway tracks with many pictorial cues
      to depth, or a photograph of a pastoral scene with fewer obvious depth cues. To
      humans, the railway tracks created a Ponzo illusion, making the upper line-appear
      longer. When the horses were allowed to choose between the photographs, they
      overwhelmingly chose the display containing the converging railway tracks.
      Control experiments ruled out alternative explanations, leading to the conclusion
      that horses are susceptible to a Ponzo illusion created by depth cues in
      photographs.

PMID- 8983052
TI  - In vitro mineral binding capacity of five fiber sources and their insoluble
      components for copper and zinc.
AB  - Five fiber-rich food sources, wheat bran (WB), rice bran (RB), oat fiber (OF),
      apple fiber (AF), and tomato fiber (TF) and their isolated insoluble fiber
      fractions were evaluated in vitro for their binding capacity for zinc (Zn) and
      copper (Cu). Endogenous Zn concentrations of the fibers varied from 11.0
      micrograms/g for OF to 136.0 micrograms/g for WB, whereas Cu concentrations
      ranged from 1.0 microgram/g for OF to 14.0 micrograms/g for WB. In all the
      fibers, total Cu bound was significantly higher than Zn. Total Cu bound ranged
      from 3687 micrograms/g for OF to 8019 micrograms/g and 8073 micrograms/g for WB
      and AF, whereas, bound Zn levels varied from 1213 micrograms/g for OF to 7121
      micrograms/g and 7166 micrograms/g for WB and RB, respectively. Significantly
      more Zn and Cu were bound by the fiber fractions than the whole fibers, probably
      due to the exposure of more binding sites on the polymers during the
      fractionation process. Generally, the fiber components of all five fibers showed
      Cu and Zn binding capacities decreasing in the order; hemicellulose A >
      lignocellulose > lignin > cellulose. A strong correlation was seen between the
      combined effects of protein, hemicellulose, and lignin contents of the fibers
      versus total Zn binding capacity and a lesser correlation with Cu.

PMID- 8983053
TI  - Biological and chemical evaluation of chick pea seed proteins as affected by
      germination, extraction and alpha-amylase treatment.
AB  - The effects of germination, extraction (double extraction with 70% ethanol and
      water at isoelectric point) and alpha-amylase treatments of chick pea seed flours
      on crude protein, total carbohydrate, protein efficiency ratio (PER), biological
      value (BV), true digestibility (TD), net protein utilization (NPU), essential
      amino acid composition, in-vitro protein digestibility (IVPD) and actual amino
      acid indices (essential amino acid index or amino acid score) were evaluated.
      Crude protein content was increased (8-149%), while total carbohydrate was
      decreased (11-62%) by germination, extraction and alpha-amylase treatments. Alpha
      amylase treatment was more efficient in reducing total carbohydrate and
      increasing the protein content than that of extraction treatment. The protein
      quality of chick pea flours as measured by PER, BV, TD, NPU, IVPD and corrected
      amino acid indices (actual amino acid indices x IVPD) was significantly improved
      by these treatments. The protein quality of germinated-alpha-amylase treatment
      was comparable with casein, while germinated-alpha-amylase treaded seeds appeared
      nutritionally superior to casein. The results indicate that the germinated-alpha
      amylase and germinated-alpha-amylase-extracted treatments could be used
      successfully as a source of concentrated high quality protein for baby food
      production. The corrected amino acid indices gave better prediction of PER, BV,
      TD and NPU (r = 93 to 97) than actual amino acid indices (r = 45 to 71). PER was
      highly correlated with corrected amino acid score (r = 0.93). The PER could be
      predicted from the following simple regression equation: PER = -1.827 + 0.0561 x
      corrected amino acid score.

PMID- 8983054
TI  - The cocoyam, Xanthosoma sagittifollium, as a potential raw material source for
      beer brewing.
AB  - A widely cultivated cocoyam variety, Xanthosoma sagittifollium, was assessed for
      its suitability for lager beer production, using malted Sorghum vulgare (white
      variety) for saccharification of the substrate. The three-mash decoction method
      was used. Results showed that the cocoyam was superior to barley and sorghum as a
      substrate because of its potentially higher carbohydrate content (71-78%)
      compared to barley (65%) and sorghum (70-73%). The percentage wort extract was
      13.3-14.5 degrees plato compared to 7-12 for barley and 13 degrees for the tuber
      crop, cassava. The kiln dried Xanthosoma sagittifollium gave a dark bager beer
      with good aroma (68%) and very good flavour (73%) when compared with a commercial
      lager beer (Monarch) as standard (100%). The alcohol content (4.16% w/v) and the
      specific gravity (1013) were within the range (4.0-6.4%) and (1011-1019),
      respectively, specified by the Standard Organization of Nigeria. Although the
      bitterness value 40 EBU, was higher than the typical range 16-30 EBU, the taste
      panel indicated this was acceptable. The pH was 4.68 compared with the standard
      4.36, while the acidity (as % lactic acid) was 0.36 compared to 0.24 for some
      commercial products.

PMID- 8983056
TI  - Physico-chemical and sensory properties of formulated syrup from black plum
      (Vitex doniana) fruit.
AB  - The fresh ripe fruit pulp and syrup, produced using the open pan evaporator, of
      Vitex doniana were analysed physico-chemically. Results show that the edible pulp
      of the ripe fruit is fairly rich in vitamin C (18.1 mg/100 ml) but acidic (pH
      4.38) and poor in protein (0.82%) and oil (0.56%). The syrup yielded a DE value
      of 52, total dissolved solids content of 67 degrees Brix and a refractive index
      of 1.4762 at 20 degrees C. The syrup was moderately viscous (2.1 Poiseuille),
      acid (pH 4.45) but relatively poor in vitamin C (2.8 mg/100 ml) and protein
      (0.3%). Sensory evaluation showed no significant difference (p < or = 0.05) in
      taste, flavor and overall acceptability between V. doniana syrup and honey. Both
      physico-chemical and sensory results indicate that the syrup was highly desirable
      and can substitute for other syrups as a nutritive sweetener.

PMID- 8983055
TI  - Biochemical response in rats to the addition of curry leaf (Murraya koenigii) and
      mustard seeds (Brassica juncea) to the diet.
AB  - Three groups with 12 weanling male albino rats were group fed for 90 days on a
      standard laboratory rat diet plus 20% coconut oil either without a supplement or
      with the addition of 10% curry leaf or 10% mustard seeds. Feed was offered at a
      level of 10% body weight. At the end of the trial, measurements were made on the
      total serum cholesterol, high density lipoproteins, low density lipoproteins, and
      very low density lipoproteins fractions, release of lipoproteins into the
      circulation, lecithin cholesterol acyl transferase activity and lipoprotein
      lipase activity. Feed intake and mean body weight of the rats on each treatment
      was not significantly different. Both spices resulted in a reduction in total
      serum cholesterol and LDL + VLDL, an increase in the HDL, lower release of
      lipoproteins into the circulation and an increase in the LCAT activity.

PMID- 8983057
TI  - Phytic acid, in vitro protein digestibility, dietary fiber, and minerals of
      pulses as influenced by processing methods.
AB  - The objective of this project was to determine the effect of various types of
      processing on selected nutrition related parameters of commonly consumed Indian
      pulses and soybean. Germination reduced the phytic acid content of chickpea and
      pigeonpea seeds by over 60%, and that of mung bean, urd bean, and soybean by
      about 40%. Fermentation reduced phytic acid contents by 26-39% in all these
      legumes with the exception of pigeonpea in which it was reduced by more than 50%.
      Autoclaving and roasting were more effective in reducing phytic acid in chickpea
      and pigeonpea than in urd bean, mung bean, and soybean. Germination and
      fermentation greatly increased the in vitro protein digestibility (IVPD). IVPD
      was only slightly increased by roasting and autoclaving of all legumes.
      Germination and fermentation also remarkably decreased the total dietary fiber
      (TDF) in all legumes. Autoclaving and roasting resulted in slight increases in
      TDF values. All the processing treatments had little effect on calcium, magnesium
      and iron contents.

PMID- 8983058
TI  - Effect of boiled barley-rice-feeding in hypercholesterolemic and normolipemic
      subjects.
AB  - Barley contains approximately 10% dietary fiber and is easily cooked with rice,
      the dominant cereal in Japan, to increase the intake of dietary fiber. This
      research involved three experiments to examine the influence of barley on blood
      lipids in human subjects. All subjects received a boiled barley-rice (50/50 w/w
      mix) supplement two times per day in place of rice for 2 or 4 weeks. In the
      normolipemic subjects, serum lipids were unaffected by the ingestion of barley
      for 4 weeks. In twenty hypercholesterolemic men aged 41 +/- 5 years, the
      ingestion of barley was associated with a significant fall in serum total
      cholesterol, LDL-cholesterol, phospholipids and LDL and VLDL-lipoproteins. In
      seven mildly hypercholesterolemic women aged 56 +/- 7 years, a significant
      improvement of serum lipid profiles was observed. The present study suggests the
      possibility that the ingestion of barley-rice could lower serum lipids in
      hypercholesterolemic subjects.

PMID- 8983059
TI  - Tumor suppressor genes and signal transduction in Drosophila.
AB  - Several studies in Drosophila have revealed the existence of loss-of-function
      mutations that lead to overproliferation of epithelial tissues. The molecular
      analysis of these tumor suppressor genes has provided important clues in the
      search for signalling mechanisms controlling growth. We discuss here two genes
      that act to control epithelial cell proliferation. Mutations in the fat locus
      cause hyperplastic imaginal disc overgrowth, in which the imaginal disc cells
      retain their epithelial structure, junctional complexes, and ability to
      differentiate. However, mutations in fat also cause defective cell-cell adhesion,
      as indicated by the separation of epithelial vesicles from the epithelial sheet
      in the mutant tissue. The fat gene encodes a giant relative of cadherins,
      providing the first evidence that this class of junction-associated molecules can
      act to regulate growth. Loss of the discs large (dlg) gene product results in
      neoplastic overgrowth of imaginal discs, causes the epithelial cells to lose
      apical/basal polarity, and prevents them from differentiating. The gene encodes a
      protein made up of a series of peptide motifs, including an SH3 and a potential
      enzymatic domain, a region homologous to guanylate kinases. The presence of these
      domains suggests a role for Dlg in guanine nucleotide-mediated signal
      transduction. The Dlg protein is restricted to a specific apical junctional
      complex in Drosophila epithelial cells, the septate junction. It is the first
      identified member of a new family of junction-associated proteins that includes
      ZO-1 and ZO-2, major components of vertebrate tight junctions. These results
      suggest that junctional contacts could play previously unrecognized roles in
      regulating the growth of epithelial tissues and that ZO-1 and/or ZO-2 may act as
      tumor suppressor proteins in humans.

PMID- 8983060
TI  - The desmosome and the syndesmos: cell junctions in normal development and in
      malignancy.
AB  - The cells of various normal and malignantly transformed tissues are connected by
      "adhering junctions"-plasma membrane domains characterized by close membrane
      membrane contact, a dense cytoplasmic plaque and, in most cases, the attachment
      of cytoskeletal filaments. On the basis of their specific ultrastructural
      organization and molecular composition, three major types of intercellular
      adhering junctions can be distinguished: 1. Adherens junctions appear in
      different shapes and sizes (zonula adhaerens, fascia adh., punctum adh.) and
      contain the transmembrane glycoprotein E-cadherin. The cytoplasmic portion of E
      cadherin forms complexes with alpha-, beta-, and gamma-catenin and plakoglobin
      which, together with other proteins such as vinculin and radicin, constitute a
      plaque at which actin microfilaments insert. 2. Desmosomes (maculae adhaerentes)
      are mostly isodiametric (diameters up to approximately 0.5 micron) membrane
      domains traversed by representatives of two types of desmosomal cadherins, the
      desmogleins (Dsg) and desmocollins (Dsc), whose cytoplasmic tails contribute to a
      dense plaque containing plakoglobin and desmoplakin I (with or without an
      alternative splice form, desmoplakin II) which anchor IFs. The specific Dsc and
      Dsg subtypes can differ in different cell types and up to three different human
      genes have so far been identified for each desmosomal cadherin. 3. Complexus
      adhaerentes are junctions of variable size and shape that occur in lymphatic
      endothelia. They have a desmoplakin- and plakoglobin-rich plaque, whose specific
      transmembrane proteins have not yet been fully elucidated but can include
      endothelial cadherin-5. In their most elaborate subform- the "syndesmos"
      connecting the retothelial cells of lymph node sinus-these junctions can occupy
      extended portions of the cell surface. The molecular arrangements in desmosomes
      and complexus adhaerentes have been studied to understand the assembly and
      disappearance of these structures. The diagnostic potential of their constituent
      proteins for cell typing in tumor diagnosis is emphasized, as is the role of
      transient junction dissociation during invasion and metastasis of carcinomas and
      the general importance of tumor cell interactions with the retothelial cell
      system in the formation of lymph node metastases.

PMID- 8983061
TI  - Cadherin-dependent organization and disorganization of epithelial architecture.
AB  - Epithelial cell layers exhibit an ordered polarized architecture. However, such
      structures are disrupted during malignant transformation, which generally
      coincides with a loss of regulate cell growth. We are investigating how the
      cadherin cell adhesion system controls these processes. Cadherins form a
      molecular complex with alpha-catenin, and beta-catenin or plakoglobin at the
      cytoplasmic side in normal cells. Lung carcinoma PC9 cells express E-cadherin.
      Although they express other catenins, they lack alpha-catenin and cannot firmly
      aggregate, suggesting that their E-cadherin is inactive. Transfection of the PC9
      cells with alpha-catenin cDNA leads to activation of the E-cadherin, inducing
      their compact aggregation. In these aggregates, an almost complete epithelial
      specific architecture is organized, including the formation of microvilli and a
      junctional complex. We also studied the effect of hepatocyte growth
      factor/scatter factor (HGF/SF) on cell-cell contacts in keratinocyte cell lines,
      and found that this growth factor can disrupt desmosomal cell-cell contacts.
      HGF/SF, and also epidermal growth factor, enhance tyrosine phosphorylation of
      beta-catenin or plakoglobin in human carcinoma lines as they induce scattering of
      these cells. These findings suggest that the cadherin adhesion system is central
      in organizing epithelial structures and that tyrosine phosphorylation of catenins
      may modulate this organization process.

PMID- 8983062
TI  - Possible involvement of adherens junction plaque proteins in tumorigenesis and
      metastasis.
AB  - The cell-to-cell adherens junction is a site for cadherin-mediated adhesion where
      actin filaments are densely associated with the plasma membrane through its well
      developed plasmalemmal undercoat, a "plaque" structure. Recently, we succeeded in
      isolating the cell-to-cell adherens junctions from rat liver, and in identifying
      some novel AJ plaque constituents, including src-like tyrosine kinases, radixin,
      alpha-catenin, and a 220kD protein. The application of genetic engineering
      techniques to AJ plaque proteins has recently generated a wealth of novel
      observations, leading to the speculation that these proteins are involved in
      tumorigenesis and metastasis. This paper reviews these findings and discusses
      some functions of the AJ plaque proteins in normal cells, as well as in
      tumorigenesis and metastasis.

PMID- 8983063
TI  - Alterations of the cadherin-catenin cell adhesion system in cancers.
AB  - The E-cadherin-mediated cell adhesion system acts as an "invasion suppressor"
      system, which is widely considered to be inactivated when the expression of E
      cadherin is reduced and/or heterogeneous. To further investigate the molecular
      mechanisms responsible for dysfunction of this system in cancers, we examined
      human carcinoma cell lines lacking tight cell-cell adhesion. In KATO-III,
      established from stomach cancer, a point mutation of the E-cadherin gene resulted
      in a mRNA splicing error and markedly reduced E-cadherin expression. In another
      stomach cancer cell line, MKN 45, an 18-bp deletion of the E-cadherin gene caused
      a mRNA splicing error and a 4-amino-acid deletion, which was considered to alter
      the conformation around the key Ca(2+)-binding motif. In these two cell lines,
      the wild-type allele of the E-cadherin locus, which was assigned to chromosome
      16q, was lost. Also in vivo, we found mutation of E-cadherin in breast cancers,
      where allele loss on chromosome 16 has frequently been reported. Thus,
      dysfunction of E-cadherin could be caused by a combination of the loss of one
      allele and a mutation in the remaining allele. Homologous deletion of part of the
      alpha-catenin gene, resulting in markedly reduced expression, was observed in a
      human lung cancer cell line, PC9. Recently, we also found mutations of beta
      catenin in human carcinoma cell lines. These findings indicate the possible
      involvement of genetic abnormalities of various components in inactivation of the
      E-cadherin-mediated "invasion suppressor system" in cancers.

PMID- 8983064
TI  - Downregulation in vivo of the invasion-suppressor molecule E-cadherin in
      experimental and clinical cancer.
AB  - The invasion-suppressor molecule E-cadherin (E-CAD) can be regulated at multiple
      levels: synthesis, processing and stability of mRNA; synthesis, processing and
      stability of protein; localization and posttranslational modification of protein;
      binding to catenins (E-CAD-associated proteins); and size and charge of cell
      surface glycosaminoglycans. Loss of E-CAD antigen and of E-CAD function in vivo
      has been observed with cell lines that homogeneously expressed functional E-CAD
      in vitro. These observations led to the idea that factors in the host may
      downmodulate E-CAD on the cancer cells, thereby promoting cell invasion. Nude
      mouse cancers that were homogeneously E-CAD-positive and noninvasive in vitro,
      formed by epithelioid MDCK or NMuMG cells, stained heterogeneously for E-CAD;
      such cancers were invasive and metastatic. The in vivo downmodulation appeared to
      be transient. Ex vivo cultures from primary cancers, as well as from metastases,
      produced homogeneously E-CAD-positive and noninvasive cells. Downmodulation did
      not occur when cells were micro-encapsulated and then implanted in the mouse,
      suggesting a role for immediate cancer cell-host cell contact. Similar in
      vitro/in vivo/ex vivo experiments with mouse MO4 fibrosarcoma cells, transfected
      with E-CAD cDNA under the control of a b-actin promotor, showed downregulation at
      the transcriptional or mRNA stability level. This downregulation was rapidly
      reversible upon ex vivo culture of the tumor cells. TGF-bl and IGF-I were found,
      respectively, to downregulate and upregulate the expression or the function of E
      CAD. We speculate that IGF-1 restores the function of E-CAD through interaction
      of the IGF-I tyrosine kinase receptor with the catenin-actin cytoskeletal
      complex. In human cancers, immunohistochemistry has revealed changes in E
      cadherin that agree with the experimental data on transient downmodulation of the
      invasion-suppressor function of E-cadherin by host factors.

PMID- 8983065
TI  - Sialomucin ligands for selectins: a new family of cell adhesion molecules.
AB  - The specific migration of various leukocyte subsets to areas undergoing
      pathogenic attack is one of the cornerstones of the immune system. Assorted
      adhesion molecules, chemokines, non-protein signalling molecules, and their
      respective receptors are utilized during this process. The combinatorial matrix
      formed by this diversity of agents determines the cell type that migrates to a
      given class of inflammatory site. The selectins are a family of adhesion
      molecules that elicit the rolling response that initiates the inflammatory
      cascade. Selectins contain a type C lectin domain at their N-termini which
      recognizes sialylated, fucosylated carbohydrate ligands of the sialyl Lewis X
      (sLex) type. Recently, it has been demonstrated that these carbohydrate ligands
      are presented by a new class of adhesion molecules that have mucin-like structure
      and have been termed the sialomucin adhesion family. The function of this new
      family of adhesion molecules is to act as a scaffold that presents selectin
      carbohydrate ligands in a clustered, tissue specific manner to allow for higher
      avidity interactions between leukocytes and endothelial cells during the
      inflammatory process. In this manner, the appropriate type of leukocyte rolls
      adjacent to an inflammatory site in a temporally correct manner. This review will
      focus on the molecular and cellular biology of the sialomucin adhesion family and
      will discuss the possible implications of these findings on the development of
      specific inhibitors of selectin function.

PMID- 8983066
TI  - Apoptosis of T lymphoma cells and its inhibition by monoclonal antibodies against
      cell surface adhesion molecules.
AB  - We previously established the malignant T lymphoma CS-21 cell line from a
      spontaneously developed lymphoma in a BALB/c mouse. CS-21 cells produce lymph
      node metastasis with a high incidence following s.c. injection. CS-21 lymphoma
      cells grew continuously when the cells were co-cultured under the cell-cell
      attached conditions with stromal cells prepared from lymph nodes. However, they
      were unable to proliferate by themselves and underwent apoptosis when separated
      from the lymph node stromal cells. To identify the cell adhesion molecules of CS
      21, we developed monoclonal antibodies (mAbs) directed against CS-21 cell-surface
      proteins. Fourteen mAbs partially inhibited the binding of CS-21 cells to a CA-12
      stromal cell monolayer. MCS-5 (mAb against CS-21 No. 5) directed against a 168
      kDa cell-membrane protein and MCS-19 against a 23-kDa protein were found to
      suppress apoptosis and stimulate CS-21 cell growth. Soluble factors secreted from
      CA-12 stromal cells enhanced CS-21 cell growth but were not sufficient to prevent
      apoptosis. In the presence of both stromal cell-secreted factors and mAbs MCS-5
      or MCS-19, CS-21 lymphoma cells resisted apoptosis and grew as quickly as in the
      co-culture with CA-12 stromal cells. Based on these results, we conclude that CA
      12 lymph node stromal cells support CS-21 lymphoma cell growth by secreting
      paracrine growth factors and presenting receptors for the 168-kDa and 23-kDa cell
      surface adhesion molecules of CS-21 cells that transmit signals to prevent CS-21
      cell apoptosis.

PMID- 8983067
TI  - Cell adhesion and tumor metastasis.
AB  - Integrins, among the various classes of cell adhesion receptors, are particularly
      associated with cell adhesion to extracellular matrices. They are heterodimeric
      transmembrane proteins with large ectodomains and short cytoplasmic tails. In
      many cases the sequence recognized by the integrins in the extracellular matrix
      proteins is the tripeptide Arg-Gly-Asp (RGD). Short synthetic peptides containing
      this sequence can inhibit tumor cell invasion in vitro and tumor dissemination in
      vivo. Because the alpha 5 beta 1 integrin appears to be the target of the
      peptides in many types of tumors, we have used phage display libraries to analyze
      the specificity of alpha 5 beta 1 and have isolated potent and specific
      inhibitors for this integrin. Increased expression of the alpha 5 beta 1
      integrin, which is a fibronectin receptor, can also suppress cell migration and
      tumor cell invasion. We suggest this effect may be mediated through increased
      deposition of fibronectin matrix around the cells, because we found that the
      fibrillar matrix fibronectin suppresses tumor cell migration. There is increasing
      evidence that signals are elicited by the binding of integrins to their target
      proteins. This possibility has generated a great deal of interest in the
      cytoplasmic molecules that might mediate the integrin-associated signaling. At
      least two kinases, a novel tyrosine kinase, focal adhesion kinase (fak), and
      protein kinase C (PKC), are activated by integrin-mediated cell attachment.
      Moreover, a phosphorylated 190 kDa protein-associated with the alpha v beta 3
      integrin has been found Anchorage dependence of cells and the migration-promoting
      activity of cell adhesion molecules are likely to depend on signal transduction
      through such molecules.

PMID- 8983068
TI  - A structural basis for bidirectional integrin signalling.

PMID- 8983069
TI  - Integrin signals and tumor growth control.
AB  - Integrins can trigger signals by activation of cytoplasmic tyrosine kinases,
      including pp125FAK. Preliminary evidence suggests that serine/threonine kinases
      such as ERKs may also be activated via integrins. Thus, there seems to be at
      least partial overlap between RTK signaling pathways and integrin signaling. In
      tumor cells, ectopic expression or over-expression of certain integrins such as
      alpha 5/beta 1 can result in reduced tumorigenesis. Presumably the effects of
      integrins on tumor growth are mediated by the integrin signaling pathway(s)
      involving FAK and ERKs. However, the precise mechanisms involved have not yet
      been elucidated.

PMID- 8983070
TI  - Prevention of cancer metastasis in mice with fibronectin-related substances.
AB  - Since the adhesive interaction between tumor cells and host cells, or
      extracellular matrix (ECM), presumably plays a crucial role in metastatic
      formation during a series of complex events, we used synthetic or recombinant
      polypeptide analogues, poly(RGD) or CH-271-based on Arg-Gly-Asp(RGD) sequence or
      functional domains in fibronectin. Use of these analogues regulated the
      mechanisms involved in cell adhesion during the metastatic process. Poly(RGD)
      effectively inhibited the experimental lung and liver metastasis when coinjected
      i.v. with different types of tumors. In a spontaneous lung metastasis model using
      B-16-BL6 melanoma, multiple administrations of this polypeptide, before or after
      surgical excision of the primary tumor, resulted in significant inhibition of
      tumor metastasis without affecting the growth of the primary tumor. Further, it
      substantially prolonged the survival time of mice. The mechanism responsible for
      the inhibition of tumor metastasis by the polypeptides is partly associated with
      the ability to interfere with cell functions such as adhesiveness, motility, and
      invasiveness in the cellular adhesive process of metastasis. The combination of
      CH-271 fusion polypeptide and anticancer drugs, i.e., anti-adhesion therapy and
      chemotherapy, caused a dramatic inhibition of lung and liver metastasis of tumors
      when compared with either treatment alone, or in the control. Since the
      polypeptides derived from cell adhesion molecules showed no short-term toxicity
      to the host, they may provide a promising approach for the control of cancer
      metastasis.

PMID- 8983071
TI  - Analysis of molecular functions of the tumor metastasis promoting surface
      molecule CD44v4-v7 using transgenic mice.
AB  - In certain circumstances, metastatic tumor cells may mimic the molecular
      properties and behaviour of lymphocytes. Support for this hypothesis has come
      from the observation that activated lymphocytes and some tumor cells need a CD44
      variant isoform (CD44v) to survive and/or expand in the lymphatic system. CD44
      variant (CD44v) isoforms are created by differential splicing from a pool of at
      least ten variant exons (v1-v10), the encoded sequences of which are absent in
      the CD44 standard isoform (CD44s). To dissect the molecular interactions of
      CD44v, transgenic animals have been generated that constitutively express a
      variant of CD44 containing sequences encoded by exons v4 to v7 on the surface of
      T cells. Lymphocytes derived from these transgenic animals show accelerated entry
      into S phase upon antigenic stimulation, and a subpopulation of the cells
      constitutively express early lymphocyte activation markers. Our data support the
      hypothesis that the presence of CD44v4-v7 on the surface of T cells mediates
      intercellular or intracellular processes which result in the promotion of T cells
      towards a preactivated state.

PMID- 8983072
TI  - Matrix-degrading metalloproteinases in tumor progression.
AB  - The matrix-degrading metalloproteinases (MMPs) have been implicated in tumor
      invasion and metastasis. Recently it has become clear that the expression of MMPs
      in tumors is frequently localized to stromal cells surrounding malignant tumor
      cells. In the mouse skin model of multi-stage carcinogenesis, the MMP stromelysin
      is expressed in stromal fibroblast-like cells surrounding benign and malignant
      squamous cell carcinomas. Conversion of these tumors to highly invasive and
      metastatic spindle-cell tumors is however, associated with the expression of
      stromelysin-1 mRNA in the tumor cells themselves. The analysis of MMPs in human
      colon adenocarcinomas at different stages of tumor progression revealed that
      matrilysin was the only MMP expressed in the tumor cells, while stromelysin-1 and
      stromelysin-3 mRNA was detected in stromal cells surrounding malignant tumor
      cells. Matrilysin mRNA is detected in benign tumors as well as malignant tumor
      cells, and the relative level and percent of tumors expressing matrilysin
      correlates with the stage of tumor progression. These results suggest that both
      stromal and tumor cell metalloproteinases may contribute to tumor invasion and
      metastasis, and also suggests that MMPs may play a role in earlier events in the
      tumor progression pathway. A potential role for MMPs in tumor growth is
      illustrated by results which suggest that the expression of matrilysin in human
      colon cancer-derived cells increases tumorigenicity following injection into the
      cecum, and that transgenic mice expressing matrilysin mRNA show a marked
      proliferative response. MMPs may therefore play multiple roles in tumor
      progression.

PMID- 8983073
TI  - Possible involvement of VEGF-FLT tyrosine kinase receptor system in normal and
      tumor angiogenesis.
AB  - A novel receptor-type tyrosine kinase gene flt (fms-like tyrosine kinase, flt-1)
      was isolated from human placenta cDNA library. Flt-1 receptor carries a ligand
      binding domain which contains seven immunoglobulin-like stretches. Further, Flt-1
      tyrosine kinase domain is separated by an approximately 70 amino acid-insert
      region similar to the cases of Fms/Kit/PDGF-R (fms family). However, unlike the
      fms family members, Flt-1 insert region does not contain "Tyr-X-X-Met" motif,
      which is known to be important for signal transduction and for the binding of P13
      kinase to the receptor. Thus, a unique structure of Flt-1 suggests that a signal
      transduction pathway from Flt receptor is different from that in the fms family.
      The expression of flt-1 gene is detectable in a variety of normal tissues, and
      cell fractionation studies indicate that the flt-1 mRNA is highly expressed in
      endothelial cell-enriched fraction. VEGF, which has recently been reported as a
      ligand for Flt-1 receptor, dramatically stimulated growth of endothelial cells in
      culture. Many human tumors were found to express VEGF mRNA but not Flt-1 message,
      suggesting a paracrine mechanism for tumor angiogenesis. Interestingly, VEGF
      could not stimulate proliferation of Flt-1-overexpressing NIH3T3 fibroblast
      cells. These results suggest that Flt-1 is an endothel-specific growth factor
      receptor and that the signal transducing pathway through Flt-1 receptor is
      inactive in the fibroblast background.

PMID- 8983074
TI  - Invasive carcinomas dismantle surrounding stroma induced to express the nuclear
      factor c-ets-1.

PMID- 8983075
TI  - Cancer-stromal interaction through growth factor/cytokine networks implicated in
      growth of stomach cancer.
AB  - Stomach cancer shows multiple gene changes, including both oncogenes and tumor
      suppressor genes. Among them, the one most frequently implicated in stomach
      cancer is the abnormal expression and amplification of the c-met gene. Moreover,
      stomach cancer cells express a broad spectrum of growth factors and cytokines
      that not only serve autocrine or paracrine growth of tumor cells, but also
      organize the complex networks between tumor cells and stromal cells. However, the
      scenario of cancer-stromal interaction differs depending on the two histological
      types-the well-differentiated or intestinal type and the poorly-differentiated or
      diffuse type-as the two types of stomach cancer may have different genetic
      pathways. The interaction between cell-adhesion molecules in the c-met
      overexpressed tumor cells and HGF from activated fibroblast may be involved in
      the progression and the morphogenesis of stomach cancer.

PMID- 8983076
TI  - Hepatocyte growth factor as mitogen, motogen and morphogen, and its roles in
      organ regeneration.
AB  - Hepatocyte growth factor (HGF) has been discovered, purified, and molecularly
      cloned as a potent mitogen for mature hepatocytes. HGF is a heterodimeric
      molecule composed of a 69 kDa alpha-subunit and a 34 kDa subunit. It contains
      four kringle domains in the alpha-subunit. It is produced by mesenchymal cells
      and predominantly acts on a wide variety of epithelial cells as a mitogen
      (stimulation of cell growth), a motogen (stimulation of cell motility), and a
      morphogen (induction of multicellular tissue-like structure). These pleiotropic
      functions of HGF are essential biological activities for the construction of
      normal tissue architecture. HGF may be one of the long-sought paracrine mediators
      of morphogenetic epithelial-mesenchymal interactions. On the other hand, HGF
      receptor was identified as the product of the c-met proto-oncogene, which encodes
      a 190-kDa transmembrane protein possessing tyrosine kinase domain. HGF mRNA and
      HGF protein are rapidly and markedly increased in the liver and plasma of rats
      with various types of liver injuries. HGF receptors on plasma membranes of the
      liver were almost completely down-regulated due to HGF binding and subsequent
      internalization. Therefore, HGF acts as a hepatotropic factor for liver
      regeneration. Recombinant HGF, intravenously injected into mice, remarkably
      enhances liver regeneration. After various renal and lung injuries, HGF mRNA, HGF
      protein, and HGF receptors in the kidney and lung are also rapidly altered prior
      to the onset of replication of renal tubular cells and lung alveolar epithelial
      cells Recombinant HGF intravenously injected into rats also remarkably enhances
      renal and lung regeneration. Thus, HGF acts as a renotropic factor in renal
      regeneration and as a plumotropic factor in lung regeneration. It is considered a
      key molecule for the construction of normal tissue structure during
      embryogenesis, organogenesis, and organ regeneration.

PMID- 8983077
TI  - Molecular aspects of the loss of cell adhesion and gain of invasiveness in
      carcinomas.
AB  - It has been realized that the loss of epithelial differentiation in carcinomas,
      which is accompanied by higher mobility and invasiveness of the tumor cells, is
      often a consequence of reduced intercellular adhesion. A variety of recent
      reports have indicated that the primary cause for the 'scattering' of the cells
      in invasive carcinomas is a disturbance of the integrity of intercellular
      junctions. It has also been suggested that during invasion, carcinoma cells
      convert to a sort of mesenchymal stage, as do normal epithelial cells during
      development. This paper discusses permanent and transient molecular mechanisms
      which lead to the impairment of junction integrity of epithelial cells and thus
      to the progression of carcinomas towards a more invasive state.

PMID- 8983078
TI  - Implication of scatter/growth factors in tumor progression.
AB  - Several steps during cancer progression have been distinguished on the basis of
      anatomo-pathological observations and experimental data. The first step, which
      consists of the detachment of the cancer cells from the primary tumor prior to
      their migration, has received much attention. Several lines of evidence have
      indicated that inducer molecules of tumor cell dispersion are scatter factors
      which are similar or identical to some growth factors. Our studies have focused
      on the dispersing effect of growth factors, such as acidic FGF (aFGF) on a rat
      bladder carcinoma cell line. These studies demonstrated that specific
      extracellular matrix components might contribute to the scattering effect of
      soluble growth factors. Additionally, our results indicated that the dispersing
      action of aFGF is counterbalanced by its mitogenic effect, since these two
      functions of aFGF cannot be observed simultaneously for the same cell. Depending
      on its location in the cell collective, a given cell chooses to enter mitosis or
      to scatter in response to aFGF. The choice between the two responses is
      apparently driven by molecules belonging to the transducing pathways of aFGF
      signaling. Finally, our data indicated that aFGF-induced tumor cell scattering
      leads to increased in vitro invasiveness and in vivo metastasis. Interestingly,
      the presence of few aFGF-producing tumor cells in a population of non-producing
      cells dramatically enhances the growth rate and the metastatic properties of the
      whole tumor, suggesting that a low proportion of highly metastatic cells in a
      heterogeneous cell population might modify the behavior of the tumor mass.

PMID- 8983079
TI  - Signaling molecules that mediate the actions of FGF.
AB  - Signaling by fibroblast growth factor (FGF) is critical for cellular growth and
      differentiation. We have studied the role of FGF and its receptor in development
      and also the signaling pathways utilized by these molecules. Transgenic mice
      expressing a dominant negative FGF receptor specifically in lung tissue fail to
      develop lungs. These findings suggest that FGF signaling is important for airway
      branching and alveolar formation. In Xenopus embryos, FGF is involved in the
      development of posterior structures. Induction of mesoderm by FGF is mediated by
      the serine-threonine kinase RAF. The expression of a dominant negative RAF
      selectively blocks the mesoderm-inducing action of FGF. Expression of activated
      RAF accentuated the development of posterior structures Other intracellular
      molecules that are involved with FGF signaling include RAS, a low-molecular
      weight GTP-binding protein. We have identified a novel gene (RIP, for RAS
      interacting protein) that contains a RAS-binding domain. This domain is found in
      at least one other protein, ralGDS. Both RIP and ralGDS bind to activated RAS
      suggesting that these proteins are likely candidates for mediators of RAS
      function. These findings help elucidate the role of FGF signaling in development.

PMID- 8983080
TI  - TGF beta regulation of cell proliferation.
AB  - The beta-type transforming growth factors (TGF beta) are potent inhibitors of
      cell proliferation. The mechanisms of TGF beta growth inhibition have been
      investigated. In skin keratinocytes, TGF beta 1 rapidly suppresses c-myc
      expression at the level of transcriptional initiation, and expression of c-myc
      was shown to be necessary for proliferation of these cells. Overexpression of c
      myc, using an inducible construct, blocks growth inhibition by TGF beta 1. In
      11.5 day p.c. lung bud organ cultures, TGF beta 1 inhibits tracheobronchial
      epithelial development, including branching morphogenesis. At this stage of
      development, the tracheobronchial epithelia express N-myc, but not c-myc, TGF
      beta 1 was shown to markedly inhibit N-myc expression in epithelia of the lung
      bud organ cultures. N-myc gene knockout experiments by others have shown that N
      myc is required for branching morphogenesis of the tracheobronchial tree. The
      data indicate that suppression of expression of either N-myc or c-myc may play a
      role in TGF beta growth inhibition. To study the role of TGF beta 1 in normal
      mammary development and in mammary neoplasia, we have constructed three
      transgenic mouse lines that express a simian TGF beta 1S223/225 mutated to
      produce a constitutively active product under the control of the MMTV
      enhancer/promoter. Expression of the transgene was associated with marked
      suppression of the normal pattern of mammary ductal tree development in female
      transgenics from all three lines. However, during pregnancy, alveolar outgrowths
      developed from the hypoplastic ductal tree, and lactation occurred. Unlike many
      other transgenic mouse models in which expression of TGF alpha or oncogenes under
      control of the MMTV promoter leads to mammary epithelial hyperplasia and
      increased tumor formation, the MMTV-TGF beta 1 transgene causes conditional
      hypoplasia of the mammary ductal tree. No spontaneous tumors have been detected
      in the MMTV-TGF beta 1 transgenic animals, indicating that overexpression of TGF
      beta 1 in mammary epithelia does not enhance, and may actually suppress, early
      stages of carcinoma development. Other studies have shown that overexpression of
      TGF beta 1 in carcinoma cells enhances tumorigenicity and metastatic spread. We
      propose that TGF beta has a bifunctional role in carcinogenesis, retarding
      carcinoma development but enhancing progression once neoplastic transformation
      has occurred and the growth inhibitory response to TGF beta has been lost.

PMID- 8983081
TI  - An emerging complexity of receptors for transforming growth factor-beta.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional protein that
      modulates cell proliferation and interaction with the extracellular matrix. Three
      common TGF-beta receptors are found on the cell surface. The type III receptor is
      a transmembrane proteoglycan with a short cytoplasmic domain and is thought not
      to be involved in TGF-beta induced signalling. In contrast, the type II and type
      I receptors are transmembrane serine/threonine kinases. The type II receptor
      determines the ligand specificity, whereas the type I receptor interacts with the
      type II receptor and may not have a ligand binding specificity by itself. Both
      type II and type I receptors are involved in TGF-beta induced signalling. The
      type II receptor, likely in conjunction with the type I receptor, is required for
      the antiproliferative effect of TGF-beta, whereas the type I receptor is the
      likely mediator of the effects of TGF-beta on the expression of several genes
      including some extracellular matrix proteins. To address the role of TGF-beta
      signalling in myoblast differentiation, we transfected a dominant negative mutant
      of the type II receptor in myoblasts, thus inhibiting type II receptor mediated
      signalling. These cells not longer had the ability to differentiate in vitro or
      in vivo, suggesting that TGF-beta signalling through the type II receptor
      provides competence for myoblastic differentiation. These studies also indicate
      that there are several signalling pathways involved in myoblastic
      differentiation, one of which is modulated by the TGF-beta signalling.

PMID- 8983082
TI  - Insights into the physiology of TGF alpha and signaling through the EGF receptor
      revealed by gene targeting and acts of nature.
AB  - Transforming growth factor alpha (TGF alpha) is one of a group of structurally
      related growth factors (the epidermal growth factor family of ligands) that
      interact with one or other members of the epidermal growth factor family of
      protein tyrosine kinase receptors (EGF-R's). A number of excellent reviews
      detailing our knowledge of this area have been recently published (Carpenter and
      Wahl, 1991; Derynck, 1992; Prigent and Lemoine, 1992). Rather than add to their
      number, this review focuses on new insights into the importance of TGF alpha and
      signaling through the EGF receptor considered in the context of the laboratory
      mouse. The new information has emerged from analysis of mutant mice generated
      either by classical gene targeting in embryonic stem (ES) cells or by accidents
      of nature. In addition to their intrinsic interest, these mice are proving
      invaluable in determining the importance of EGF receptor signaling in wound
      healing and as a contributing factor in the conversion of a normal cell into its
      tumorigenic counterpart.

PMID- 8983083
TI  - Epidermal differentiation and keratin gene expression.
AB  - Epidermal keratinocytes are ideal as a model system for the study of mammalian
      differentiation because primary cells have a high proliferative capacity and can
      be cultured under conditions enabling a balance of growth and differentiation. In
      addition, epidermal keratin genes have been cloned and characterized, and their
      strong promoters provide a means of high-level expression of transgenes in the
      epidermis of mice. For these reasons, considerable headway has been made in
      recent years in the quest to elucidate the biological pathways involved in the
      control of epidermal growth and differentiation. An understanding of these
      mechanisms is essential to realizing the potential of epidermal keratinocytes for
      drug delivery and gene therapy. This paper reviews what is presently known about
      epidermal growth and differentiation, with emphasis on the expression of
      epidermal-specific genes.

PMID- 8983084
TI  - Tyrosine kinase signalling pathways.
AB  - Protein-tyrosine kinases act as receptors for a wide range of external signals
      that control the growth and differentiation of normal cells. Additionally, many
      retroviral and cellular oncogenes encode tyrosine kinase variants that are
      constitutively active. Recent evidence suggests that the intracellular targets of
      tyrosine kinases contain a protein module of approximately 100 amino acids, the
      Src homology 2 (SH2) domain. SH2 domains directly recognize tyrosine
      phosphorylation sites, and are thereby recruited to activated, autophosphorylated
      growth factor receptors. These interactions, in turn, stimulate the biochemical
      signalling pathways that control gene expression, cytoskeletal architecture, and
      cell metabolism. SH2-containing proteins frequently contain a distinct element of
      approximately 50 residues, the SH3 domain, that recognizes proline-rich motifs.
      Proteins with SH2 and SH3 domains can act as adaptors to couple tyrosine kinases
      to downstream targets with SH3-binding sites. A specific example of the
      synergistic action of SH2 and SH3 domains involves regulation of the Ras pathway
      by the adaptor protein Sem-5/drk/Grb2, which links tyrosine kinases to the Ras
      guanine nucleotide releasing protein Sos, which converts Ras to the active GTP
      bound state.

PMID- 8983085
TI  - Non-receptor tyrosine kinases in mammalian neurogenesis.
AB  - Several members of the Src family of non-receptor tyrosine kinases are expressed
      at high levels in embryonic neural tissues as well as in adult brain. Relatively
      little has been known, however, about their roles in neural development. Attempts
      to clarify this by production of mutant mice have been unsuccessful because of
      gene redundancy. We earlier isolated a new cytoplasmic protein tyrosine kinase,
      Csk, and showed that it inactivates uniquely all members of non-receptor tyrosine
      kinases in vitro. Here, we have generated Csk-deficient mouse embryos and shown
      that Csk is indeed an indispensable negative regulator for all non-receptor
      tyrosine kinases in vivo, and that regulated activity of these kinases is
      essential for normal development of mice at the neural stage. The signaling
      pathway through Src-family kinases during neurulation is also discussed.

PMID- 8983087
TI  - Alterations of beta-endorphin-like immunoreactivity in CSF following behavioral
      training using a passive avoidance procedure.
AB  - The central opioid system may have an important influence on memory processes. In
      view of this, the concentration of beta-endorphin-like immunoreactivity (beta
      ELIR) in cerebrospinal fluid (CSF) was measured by a radioimmunoassay in rats
      trained in a passive avoidance procedure. The beta-ELIR in CSF was examined
      immediately, 2, 5, 10, and 30 min after the learning trial in which rats were
      exposed to footshock (0, 0.25, or 1.0 mA for 3 s). Avoidance latency and beta
      ELIR in CSF were examined 24 and 120 h after the learning trial. The beta-ELIR in
      CSF was increased at 5 min after the learning trial in rats exposed to footshock
      of 0.25 mA. The beta-ELIR in CSF was elevated at 5 and 10 min, followed by a
      significant decrease at 30 min after the learning trial in rats exposed to a
      footshock of 1.0 mA. Thus, although an increase in beta-ELIR in CSF was not, the
      duration of the increase was, related to the shock intensity. Interestingly, a
      decrease followed the increase in beta-ELIR in CSF which was significant only in
      rats exposed to the high shock intensity. Avoidance latencies were enhanced in a
      shock intensity-dependent manner at both 24 and 120 h retention tests. No change
      in beta-ELIR in CSF was found during retention trials. The results suggest that
      behavioral manipulations alter beta-ELIR in CSF. An increase in beta-ELIR in CSF
      may be highly associated with stressful and emotional responses during behavioral
      training.

PMID- 8983086
TI  - Rho small G protein and cytoskeletal control.
AB  - The Rho family belongs to the Ras-related small GTP-binding protein (G protein)
      superfamily and regulates various cell functions in which the actomyosin system
      is involved, including cell morphology, membrane ruffling, cell motility, cell
      aggregation, cytokinesis, smooth muscle contraction, and yeast budding. Three
      GDP/GTP exchange proteins (GEPs), named Smg GDS, Dbl, and Rho GDI, and two GTPase
      activating proteins (GAPs), named Rho GAP and p190 associated with Ras GAP, have
      been identified. The Rho activity is likely to be regulated by protein kinase C
      which is linked through phospholipase C to the tyrosine kinase-type membrane
      receptors and the heterotrimeric G protein-linked receptors. It is likely that
      both Ras and Rho receive signals from the membrane receptors through different
      pathways and transduce signals to genes and cytoskeleton, respectively. In
      carcinogenesis, mutational activation of any component in the Ras signaling
      pathway may cause abnormal cell proliferation, whereas mutational activation of
      any component in the Rho signaling pathway may cause invasiveness and metastasis
      of carcinoma cells.

PMID- 8983088
TI  - Corticosteroid receptor mediated effects on mood in humans.
AB  - The present double-blind cross-over study aimed to discriminate effects of
      dexamethasone (DEX) and cortisol (CORT) on mood in ten healthy men. DEX is
      assumed to predominantly activate glucocorticoid receptors (GR) whereas CORT
      binds central nervous mineralocorticoid receptors (MR) as well as GR. Mood was
      assessed by an extensive adjective checklist (Eigenschaftswoerterliste) every
      morning during two 7-day experimental periods. During one of these periods,
      subjects were subchronically treated with placebo, during the other they received
      DEX (4 mg/day). On days 5 and 7 of these periods, (in a balanced manner) either
      placebo or CORT (10 mg/h) was infused during the night (9 h) before mood
      assessment. DEX, acutely, enhanced activation, concentration, and arousal (p <
      .05). During prolonged DEX administration, the energizing effect of the
      glucocorticoid decreased, but emotional arousability and negative feelings
      (anger, sadness) were significantly enhanced. CORT administered during prolonged
      DEX treatment, counteracted these negative feelings, and enhanced scores on a
      dimension of "high spirits". Sole administration of CORT also enhanced "high
      spirits" (p < .05) and, like DEX, activation and concentration (p < .05). Results
      suggest GR to mediate an energizing effect and, with prolonged activation, a
      dysphoric influence on mood. Predominant activation of MR appears to mediate
      changes towards euphoric mood.

PMID- 8983089
TI  - Hormonal response to stress in brittle diabetes.
AB  - Acute psychological stress may play a role in the glycaemic instability of some
      patients with type I diabetes through an increased secretion of insulin
      counteracting hormones. To examine the validity of this hypothesis, we subjected
      to a video-recorded public-speaking stress seven healthy persons, six type I
      diabetics with stable blood glucose levels and six type I diabetics with unstable
      or brittle diabetes (with more than 10 hypoglycaemia/month and frequent
      hyperglycaemia). During the test and on a control day, heart rate, blood
      pressure, plasma ACTH, cortisol, catecholamines and prolactin were measured. The
      comparison between the stable and unstable diabetics during the stress session by
      two-way analysis of variance (group/time) showed a significant difference for
      heart rate, blood pressure, ACTH and cortisol. Psychological interview showed
      that most unstable diabetics perceived a link between life stress and their blood
      glucose control. The unstable patients had much more difficulty in verbalizing
      their emotions. Our study shows that the two groups of diabetic patients display
      distinct cardiovascular and neuroendocrine responses to psychological stress, as
      well as distinct psychological profiles. In conclusion, hormonal response to an
      acute psychological stress is more pronounced in brittle diabetes and might be
      one of its pathogenic factors.

PMID- 8983090
TI  - Sexual arousability and the menstrual cycle.
AB  - We have repeated a study of the objective (labium minus temperature) and
      subjective (semantic scales) changes in sexual arousability over the menstrual
      cycle to erotic video stimulation in 20 women with natural cycles. We extended
      the study with concomitant vibrotactile stimulation of the clitoral region. In an
      earlier study women tested for the first time in their follicular phase were
      sexually more aroused (as indicated by greater increase in labium minus
      temperature) than women tested for the first time during their luteal phase. When
      these women were retested in their alternative phase of the menstrual cycle,
      those who were then follicular did not score higher than those who were then
      luteal. We then postulated the involvement of a cognitive or conditioned
      phenomenon which was responsible for the women's repeating their initial phase
      dependent response when tested the second time in their alternative phase of the
      cycle. Identical results were obtained in the present study as far as sexual
      arousability is concerned during the first test, i.e. follicular women generally
      scored higher than luteal women; this difference in response persisted during the
      second test. Concomitant vibrotactile stimulation had no effect on labium minus
      temperature change but raised subjective sexual arousal and caused a 'more
      pleasurable' response to the erotic video. Subjective sexual and subjective
      genital arousal were positively correlated, but neither was significantly
      correlated with labium minus temperature change. The relationship between
      menstrual cycle phase and sexual arousal was further substantiated by the
      reported greater increase in sexual desire after the first erotic video in
      follicular women than in luteal women. This increased desire, as well as more
      erotic fantasies, persisted during the next 24 h. In conclusion, studies into
      effects of menstrual cycle phase on sexual arousability in the laboratory should
      seriously consider the possible learning and conditioning effects as suggested by
      the present investigation.

PMID- 8983091
TI  - A nose-brain pathway for psychotropic peptides: evidence from a brain evoked
      potential study with cholecystokinin.
AB  - The access of substances to the brain is of particular relevance for the etiology
      and treatment of psychiatric and neurologic diseases. This study provides
      functional evidence for a direct access of peptides to the human brain after
      intranasal administration. Effects were compared of intranasal (IN, 10
      micrograms) and intravenous (i.v., 0.25 and 2.5 micrograms) administered
      cholecystokinin-8 (CCK) on the auditory event related potential (AERP) in 20
      healthy subjects. Also, plasma concentration of cortisol and ACTH were monitored.
      The study was designed as a placebo-controlled, double-blind within-subject cross
      over comparison. AERPs were recorded while the subject performed on an attention
      task (oddball task). Plasma CCK concentrations after IN administration of CCK
      were comparable to those after i.v. administration of 0.25 microgram CCK, but
      were substantially lower than those after 2.5 micrograms CCK. The P3 complex of
      the AERP was markedly increased following the IN administration of CCK (p < .01)
      compared to placebo and to the i.v. administration of 0.25 microgram. This
      pattern was more obvious in women than men. Increases in plasma ACTH
      concentrations after CCK reached significance selectively following the IN mode
      of administration (p < .01).

PMID- 8983092
TI  - Health care regulation in the United States.

PMID- 8983093
TI  - Children of psychosocial risk-mothers: life events, social interaction, and
      behaviour problems at the age of 8 years.
AB  - The number of stressful life events experienced as measured on the modified
      Swedish version of Coddington's questionnaire, and the presence of behaviour
      problems assessed by Achenbach's Child Behavior Check List (CBCL) were studied in
      45 eight-year-old children of identified psychosocial risk-mothers. The mothers'
      social network was estimated using the Swedish version of Unden and Orth-Gomer's
      Interview Schedule for Social Interaction (ISSI). These mothers had been
      identified during early pregnancy. A control group of 57 children of the same age
      and their mothers without the presence of psychosocial risk-criteria was used as
      reference. The results indicated that the index children had experienced
      significantly more life events, and displayed significantly more behaviour
      problems than the reference children. The mothers in the index group had a
      significantly poorer social network than the mothers in the reference group. The
      study suggests that children of mothers, identified early on psychosocial risk
      criteria develop suboptimally. Therefore, early interventions are of great
      importance.

PMID- 8983094
TI  - A comparative review of psychosocial and occupational environment in native
      Swedes and immigrants.
AB  - The aim of the present study was to evaluate potential differences in
      psychosocial status and work environment between native Swedes and immigrants
      living in Gothenburg, Sweden. A number of psychiatric, occupational and socio
      economic factors were analysed by questionnaire in 1040 men born in 1944 out of
      1302 selected. The immigrants (n = 182) who participated in the study used
      psychopharmacological drugs more extensively than native Swedes. They were more
      dissatisfied, had traits of depression, frequent sleeping problems, dyspepsia and
      headaches compared with the native Swedes. The immigrants were more often out of
      work, and those who were gainfully employed were more dissatisfied with their
      current work and their colleagues, had a lower influence on the work situation,
      felt a lower degree of work demands, more seldom attempted to alter their work
      situation when having problems, and had a more frequent desire to change their
      type of work. Furthermore, immigrants more often than Swedes were living under
      poor housing standards, indicating a low socio-economic status. They felt a low
      degree of time pressure and had more often experienced a serious life event
      compared to native Swedes. It was concluded that immigrants were more affected by
      psychiatric, occupational and socio-economic disabilities and handicaps than
      native Swedes, indicating that immigrants are a vulnerable group in Swedish
      society.

PMID- 8983095
TI  - Foreign- and Swedish-born diabetic patients--a population-based study of
      prevalence, glycaemic control and social position.
AB  - In this study foreign- and Swedish-born individuals with diabetes mellitus were
      compared regarding prevalence and characteristics. In a Swedish county 1,568
      patients aged 20-64 years were identified, of whom 97.4% were included (143
      foreign- and 1,384 Swedish-born) in the study of medical records. There was no
      difference in prevalence of diabetes (1.4% (95% CI 1.2-1.7%) vs 1.5% (95% CI 1.4
      1.6%) but diagnosis at or after the age of 30 years was more common in foreign
      born patients (p < 0.001). They were also less often treated with insulin (p <
      0.001), had shorter duration of diabetes (p < 0.001), were more often classified
      as having a low social position in Sweden (p < 0.001) and less often controlled
      in specialized diabetes care departments (p < 0.001, 18% vs 43%). There was a
      higher occurrence of albuminuria among foreign-born women (p < 0.05). No
      differences were found in glycaemic control, but low social position was related
      to poor glycaemic control independent of being foreign- or Swedish-born, and it
      seems to be more important than place of birth.

PMID- 8983096
TI  - Physical disease among 21 suicide cases: interviews of relatives and friends.
AB  - In an earlier study made in Uppsala, it was found that in 17% of suicide cases
      there was a correlation between the suicidal act and serious physical disease. To
      obtain a deeper knowledge of this, an interview study among relatives and/or
      friends of 21 patients who had committed suicide was performed. Variables studied
      were: demographic data, somatic diagnoses, psychiatric diagnoses, contact with
      the medical sector, earlier suicidal signals, and the correlation between the
      suicidal act and the physical disease. The provision of inadequate medical
      treatment was sought. The persons who had committed suicide were allocated to one
      of three groups according to the degree of correlation between suicidal act and
      physical disease. "Very strong" correlation was found for five persons, "rather
      strong" for nine persons, and "weak" for five persons. We found that physical
      disease was seldom decisive for the suicidal act. Medical treatment was
      experienced as inadequate in nine cases. Since there is reason to believe that
      physical disease is an important complicating risk factor for suicide, it is
      important to be aware of anxiety in patients and their relatives, give plenty of
      time for information, show empathy and give the care-providers a sense of
      security to avoid suffering and reduce suicidal acts.

PMID- 8983097
TI  - Epithelial, possibly precancerous, lesions of the lung in relation to smoking,
      passive smoking, and socio-demographic variables.
AB  - We have undertaken an autopsy-based study to evaluate the etiologic importance of
      active and passive smoking, as well as socio-demographic variables, in the
      development of pathologic precursors of lung cancer. Lung specimens were taken at
      autopsy from 531 persons who had died within four hours from a cause other than
      respiratory or cancer in Athens (Greece) or the surrounding area. Specimens were
      examined blindly for basal cell hyperplasia, squamous cell metaplasia, cell
      atypia and mucous cell metaplasia, i.e., pathological entities considered as
      epithelial, possibly precancerous, lesions (EPPL). Interviews were conducted with
      next of kin of the deceased. Suitable autopsy specimens as well as completed
      interviews were eventually available for 275 subjects. EPPL score was regressed
      on the available independent variables. EPPL score was higher among active
      smokers than among nonsmokers, while ex-smokers occupied an intermediate
      position. Conditional on smoking habits, EPPL score was higher among women than
      among men and higher among manual than among non-manual workers, in agreement
      with the corresponding patterns with respect to lung cancer. Nonsmoking women
      married to ever smokers had significantly higher EPPL score than those married to
      never smokers. The overall findings of this study suggest that EPPL is a valuable
      indicator of lung cancer risk and that exposure to environmental tobacco smoke is
      associated with higher EPPL levels and therefore with higher lung cancer risk.

PMID- 8983098
TI  - National health insurance consumption and chronic symptoms following mild neck
      sprain injuries in car collisions.
AB  - OBJECTIVE: To map the extent of sick leave and number of claims made for health
      insurance among persons who had suffered neck sprain (whiplash) injuries in
      traffic accidents, and to map subjective feeling of health and quality of life
      among patients several years after the injury. DESIGN: A retrospective study of
      neck sprain injuries after car accidents and a comparison to the patients' use of
      sick leave caused by neck pain prior to the accident. SETTING: The Emergency
      Clinic at The University Hospital in Trondheim, Norway. SUBJECTS: 426 patients
      with neck sprain injuries after car accidents during 1985-1990. MAIN OUTCOME
      MEASURES: Information from Trondheim Social Security office about sick leave, and
      results from 345 patients who answered a questionnaire with respect to quality of
      life measures. RESULTS: 27% had been reported sick during the period after the
      car accident, and 5% had claimed health insurance, 58% reported sustained
      symptoms linked to the accident. CONCLUSIONS: Many reported sustained symptoms
      after neck sprain injuries, 16% of them reported being in a bad state of health.

PMID- 8983099
TI  - Health behaviour, social integration, perceived health and dysfunction. A
      comparison between patients with type I and II diabetes and controls.
AB  - This survey compared diabetic patients (n = 953) and population controls (n =
      2366) in terms of socioeconomic and occupational factors, family life, leisure
      activity, health habits, perceived social support and quality of life. The
      differences between type I and type II diabetic patients and controls were
      examined by proportions adjusted for age. Type II diabetic men had a lower
      educational level and were more often retired, unemployed or unmarried than
      controls. Type II diabetics were also less likely to have fewer healthy behaviour
      patterns than controls. Type I diabetics assessed their social support as
      inadequate slightly more often than controls, though no major differences in
      perceived availability of social support were detected between study groups. Both
      diabetic groups reported a lower health-related quality of life than healthy
      controls. Thus a chronic illness such as diabetes seems to tax the individual's
      personal resources, leading to lower quality of life.

PMID- 8983100
TI  - Injuries during leisure physical activity in a Swedish municipality.
AB  - The objective of this study was to provide an epidemiologic basis for planning
      community programmes preventing injuries during leisure physical activity,
      especially participation in sports. A total population survey of unintentional
      injuries was carried out in an area with a population of over 41,000. All sports
      injuries (n = 933) occurring within a 12-month period and requiring medical care
      were noted, giving a ratio of 22.5 per 1000 inhabitants. The majority of the
      injuries occurred in soccer (38.9%), followed by injuries in
      basketball/volleyball/handball (10.9%), and bandy/hockey (9.2%). The results
      correspond to previous studies in southern Scandinavia. In northern communities,
      the proportion of injuries in winter sports has been shown to be higher.
      Identification of these similarities and differences between the studies makes it
      possible to use the findings together in the design of general community-based
      sports injury prevention programmes suited to northern European conditions.

PMID- 8983102
TI  - The concept of anatomy--classical topographic anatomy.

PMID- 8983101
TI  - Road characteristics and bicycle accidents.
AB  - In Umea, Sweden, defects in the physical road surface contributed to nearly half
      of the single bicycle accidents. The total social cost of these injuries to
      people amount to at least SEK 20 million (SEK 60,000 or about USD 8,500 per
      accident), which corresponds to the estimated loss of "eight life equivalents a
      year". Improved winter maintenance seems to have the greatest injury prevention
      potential and would probably reduce the number of injuries considerably, whereas
      improved road quality and modification of kerbs would reduce the most severe
      injuries. A local traffic safety program should try to prevent road accidents
      instead of handling the consequences of them. In accordance with Parliament
      decisions on traffic we would like to see increased investment in measures
      favoring bicycle traffic, where cycling is seen as a solution, not as a problem.

PMID- 8983103
TI  - Anatomic basis of the lower trapezius musculocutaneous flap.
AB  - Differences in the description of the blood supply of the lower trapezius m. and
      the fact that all former findings are based on very few cases caused us to
      reinvestigate the arterial supply of the lower trapezius m. Based on the anatomic
      investigation of 70 human cadavers, the trapezial branch of the dorsal scapular
      a. was found to be the constant vessel to the lower trapezius m. The origin of
      the dorsal scapular a., however, was found to be very variable. In 45% it was a
      direct branch of either the subclavian a. or the costocervical trunk. In the
      remaining 55% the dorsal scapular a. formed different trunks with the superficial
      cervical a. and/or suprascapular a. branching off either the subclavian a., the
      thyrocervical trunk, or the internal thoracic a. Additional segmental
      musculocutaneous perforators also supply the lower part of the trapezius m. and
      the overlying skin. Consequently, the lower or ascending part of the trapezius m.
      has a vascular pattern type V. Thus, the lower trapezius musculocutaneous flap
      merits consideration in head and neck reconstruction.

PMID- 8983104
TI  - Anatomic bases of a vascularized allogenic knee joint transplantation: arterial
      blood supply of the human knee joint.
AB  - The vitality of a graft in a vascularized allogenic knee joint transplantation in
      humans will depend strongly on maintaining the arterial blood supply to the bone.
      As can be demonstrated in injected specimens on cadavers, only periostal aa. are
      important to ensure the blood supply of the human knee joint. The main arteries
      have defined nutritive areas. According to our results access to the vessels
      should most probably be conducted from the dorsal side of the knee. During the
      explantation the popliteal a. should be ligated proximally as high up as possible
      and distally just above its trifurcation. The articular branch of the descending
      genicular a. of both the donor and the recipient can be ligated because of a rich
      anastomotic network. The medial and lateral inferior genicular aa. of the donor
      should be ligated ventrally as far forward as possible. One should, above all,
      preserve the medial inferior genicular a. of the donor in order not to endanger
      the medial part of the distal segment of the graft. If an operation is to be
      performed according to the results of our anatomical studies, vascularized
      allogenic knee joint transplantations should be successful from an anatomical
      point of view.

PMID- 8983105
TI  - An unusual clinical presentation of bilateral schizencephaly.
AB  - We present a case with a characteristic magnetic resonance image (MRI) of
      bilateral open-lipped schizencephaly and atypical clinical presentation. The
      patient is still alive and in good health in her forties, she has never presented
      seizures, and although the motor dysfunction is well correlated with cerebral
      lobe involvement, neurobehavioral dysfunction is not proportional to the MR image
      of the cerebral malformation.

PMID- 8983106
TI  - Microsurgical anatomy of the anterior choroidal artery.
AB  - In this study, the authors present the results of 50 dissections of the anterior
      choroidal a. in man. Fifty cerebral hemispheres were prepared with the classic
      techniques of preservation and vascular injection. An ectopic origin was observed
      in 4% of cases. The intracisternal segment of the anterior choroidal a. forms a
      neurovascular bundle with the optic tract and basal v. Most of its
      intraparenchymatous branches arise from the cisternal segment, while branches
      supplying the optic tract, lateral geniculate body and thalamus arise from the
      intraplexual segment. Constant anastomoses exist with the vertebrobasilar system,
      specially the postero-lateral choroidal and posterior cerebral aa. We discuss the
      importance of an adequate knowledge of the anatomy of the anterior choroidal a.
      and its relations in the surgical approach to arterial aneurysms and
      arteriovenous malformations of the region.

PMID- 8983107
TI  - The abdominal linea alba: an anatomo-radiologic and biomechanical study.
AB  - Traditionally, the linea alba represents the principal route of approach in
      abdominal surgery and in consequence it is the commonest site of incisional
      hernia. The aim of this study was to review its morphology and to study its
      mechanical parameters of resistance, deformation and elasticity in order to
      compare these with the prosthetic materials most often used in the treatment of
      incisional hernia. Forty fresh cadavers were dissected and tests with a
      dynamometer and "bursting strength tester" were performed on samples taken from
      the linea alba at three levels: supra-umbilical, subumbilical and umbilical.
      Forty abdomino-pelvic scans were analysed. The morphologic results allowed
      definition of diastasis of the rectus mm. in terms of subject age: below 45 years
      of age diastasis was considered as a separation of the two rectus mm. exceeding
      10 mm above the umbilicus, 27 mm at the umbilical ring and 9 mm below the
      umbilicus; above 45 years of age the corresponding values were 15 mm, 27 mm and
      14 mm respectively. In the biomechanical study the subumbilical region exhibited
      a coefficient of elasticity greater than that of the supra-umbilical portion, but
      no significant difference in resistance was found between the different parts
      studied. The biomechanical results are compared with the corresponding data for
      prosthetic materials.

PMID- 8983108
TI  - An anatomical study of the sigmoid sulcus and related structures.
AB  - Variations in the shape and size of the sigmoid sulcus were investigated in 561
      temporal bones (438 isolated temporal bones, 49 skull bases and 25 half skull
      bases) and measurements of related structures were made. Right-left differences
      were analysed. The sigmoid sulcus was significantly wider (12 mm) and longer (38
      mm) in the skull bases, while no differences were observed in the isolated
      temporal bones. The distance from the most prominent point of the mastoid process
      to the Frankfort horizontal plane (FHP) was 33 mm; no right-left difference was
      found. The distance from the genu of the sigmoid sulcus to the external acoustic
      meatus was 24.06 mm on the right side and 24.74 mm on the left side and this
      difference is significant, being considerably longer on the left side. The
      jugular foramen diameter was 7.8 mm; no right-left difference was observed. The
      relationship of the mastoid air cells to the sulcus was analysed and air cells
      were found just behind the sulcus in 66% and behind and posterior to the sulcus
      in 5% of temporal bones.

PMID- 8983109
TI  - Theoretical situation of brain white matter tracts evaluated by three-dimensional
      MRI.
AB  - An accurate knowledge of cerebral anatomy is important in order to evaluate the
      precise location of a cerebral lesion. Cortical structures are identified by
      knowledge of the adjacent gyri and sulci; however, white matter tracts are
      difficult to differentiate from one another due to the lack of clear anatomic
      landmarks. Therefore, even if MRI shows obvious white matter abnormalities, in
      some cases it is difficult accurately to localize the lesion. The purpose of this
      study is to evaluate the location of the main white matter tracts by using three
      dimensional MR imaging. MRI study was performed by 1.5 Tesla (Signa: General
      Electric). Computer assisted analysis with Voxtool software (General Electric)
      was used to generate both surface brain and tomographic images. The exact
      anatomic basis of white matter signal abnormalities is important when analyzing
      patients with disconnective syndromes or neuropsychological deficits such as
      conduction aphasia, visuospatial deficit etc. This preliminary attempt at
      constructing a three-dimensional MRI white matter atlas of the brain may be
      helpful for evaluating the anatomico-clinical correlations in these patients, and
      also as teaching materials for the clinical (neurologic, neurosurgical), anatomic
      and radiographic disciplines.

PMID- 8983110
TI  - Magnetic resonance angiographic analysis of atlanto-axial rotation: anatomic
      bases of compression of the vertebral arteries.
AB  - The aim of this study was to identify the functional anatomic factors involved in
      the maintenance or disturbance of flow in the vertebral aa. during atlanto-axial
      rotation. Fourteen healthy volunteers were studied by magnetic resonance
      angiography (MRA) by a three-dimensional sequence in phase contrast centered on
      the vertebral aa. at the level of the cranio-cervical junction before and after
      left rotation of the head. A decrease in the signal intensity of the arterial
      flow was sought for. The results were compared to the posterolateral development
      of the loop of the vertebral a. in its atlanto-axial segment in neutral position,
      and to the measurement of the angular opening between the atlas and axis in
      dynamic position. Seven subjects also had a three-dimensional CT study (3D CT) of
      the bony relations of C1 and C2 after rotation. In 4 subjects a disturbance of
      flow in the right vertebral a. was observed in the transverse foramen of C2. This
      occurred when two factors were combined: an under-developed atlanto-axial
      arterial loop and a C1-C2 angle exceeding 35 degrees in maximal rotation. In the
      other subjects a well-developed arterial loop and/or a C1-C2 angle of less than
      35 degrees in maximal rotation were factors preserving the arterial flow. The
      risk factor associated with the C1-C2 angle seemed correlated in 3D CT with loss
      of the usual asymmetric character of rotation. A clinical application is reported
      with a case combining chronic rotational dysfunction of the cranio-cervical
      junction as shown by 3D CT and complete compression of the vertebral a. in MRA,
      confirmed by conventional angiography. A knowledge of this physiopathologic
      mechanism allows clinical detection and evaluation of the risk of any effect of
      pathology of the cranio-cervical junction on the vertebral a.

PMID- 8983111
TI  - Pontine veins. MRI cross-sectional anatomy.
AB  - The pons is covered by a rich venous network offering numerous vascular landmarks
      in MRI and during surgery. We present an original study of the veins as they
      appear on MR multiplanar scans after gadolinium IV injection. This prospective
      study is based on 40 consecutive patients with normal posterior fossa structures.
      One of the major venous collectors follows the pons: the superior petrosal v. was
      identified on MRI in 95% of our cases. Its hooklike extremity drains into the
      superior petrosal sinus. The inferior petrosal v. was never identifiable. The
      superficial pontine venous network are identified in 72.5% of cases in the axial
      plane and were organised in longitudinal and transverse collectors, whose MR
      aspects are presented here.

PMID- 8983112
TI  - The subarachnoid space surrounding the optic nerves. An ultrasound study of the
      optic nerve sheath.
AB  - The presence of enlarged optic nerve sheaths (ONS) suggests that raised
      intracranial pressure is transmitted to the perineural subarachnoid space (SAS).
      This phenomenon has gained interest because ultrasound methods are able to
      quantify the optic nerve sheath diameter (ONSD) in-vivo non-invasively with a
      resolution below 0.5 mm. In order to study the normal variation and
      distensibility of the human ONS. Histologic techniques and sonographic
      measurements were applied to 54 human optic n. specimens before and after
      exposure to pressure. In untreated postmortem specimens, the largest diameters
      were found 3 mm behind the globe (baseline range: 2.1 to 4.8 mm). Following
      volume injection into the orbital perineural SAS, all n. sheaths were enlarged
      (maximum ONSD 6.5 mm). The sheath expansion affected predominantly its anterior
      section (mean 1.6 mm, e.g. 50.2%); the posterior regions showed markedly less
      dilatation (31.6%). No relation was found between the change of ONSD and the
      baseline diameter. Variance analysis of the sonographic results showed that the
      observed ONSD change depends on (a) the position of measurement along the nerve,
      as well as on (b) the origin of the nerve (different/same subject), whereas
      lateral (left/right) or inter-investigator differences proved negligible. Our
      results suggest that individual factors determine both baseline sheath diameter
      and distensibility. The different extent of pressure-induced sheath expansion
      along the nerve may be partly due to the non-uniform distribution of subarachnoid
      trabecular fibers between nerve and sheath. In conclusion, measurements of the
      ONSD for clinical purposes should be targeted to the region immediately behind
      the globe. Under conditions of raised pressure around the intraorbital optic n.,
      bilateral ONSD measurements should give comparable findings.

PMID- 8983114
TI  - A case of muscle subclavius posticus with special reference to its innervation.
AB  - A subclavius posticus muscle was found in the left side of a Japanese male
      cadaver. This muscle arose from the first costal cartilage, inserted to the upper
      margin of the scapula, and was innervated by a branch from the nerve to the
      subclavius. This excess intermediary muscle between the subclavius and the
      inferior belly of the omohyoid appears to be more closely related to the
      subclavius, based on detailed examination of the innervation of this muscle. A
      possible schematic model of the origin of this muscle is proposed.

PMID- 8983113
TI  - Computer morphing of scanning electron micrographs: an adjunct to embryology
      teaching.
AB  - Traditional embryology courses demand considerable expenditure of time and effort
      from students to master the spatial awareness skills necessary to create three
      dimensional mental images from two-dimensional serial sections. Then students
      must imagine a movie sequence of the changes which take place during normal
      development. Further steps are required to relate this information to the
      clinical situation. As more medical and dental schools move towards problem-based
      curricula, more efficient methods of improving understanding of embryology are
      needed. The development of many organs can be studied using scanning electron
      micrographs of embryos at different ages. These high quality images are more
      easily interpreted by our students than histological sections and the
      understanding achieved more readily applied to clinical problems. Still more
      beneficial would be the provision of moving images showing the actual changes
      happening. We decided to use computer morphing techniques to prepare movie
      sequences showing development of the face and plate. For each, four scanning
      electron micrographs of appropriately-sized sheep embryo heads were taken at the
      same magnification and orientation to use as start and end points of morphing
      sequences. After using retouching techniques to colour the separate processes,
      further sequences were prepared. The discipline of maintaining the same
      magnification throughout and the possibility of directly observing changes
      between stages revealed some surprising growth patterns. This technique is
      adaptable to any area of biological development where pre- and post-illustrations
      are available. Animations can be presented on computer or on video and
      incorporated into programs. Student feedback has been very favourable.

PMID- 8983115
TI  - Hepaticocystic duct--a case report.
AB  - A case of an anomalous extrahepatic biliary system is reported in which the
      common hepatic duct was found to enter the gallbladder, whereas the cystic duct
      drained the entire biliary system into the duodenum. In this case, the gangrenous
      gallbladder was removed and the continuity between the common hepatic duct and
      the gastrointestinal tract was restored by means of Roux-en-Y anastomosis. The
      identification and treatment options of this rare anomaly are briefly discussed.

PMID- 8983116
TI  - Gigantic patent ductus arteriosus--report of a newborn cadaver dissection and
      review of the literature.
AB  - During the gross anatomical dissection of the thoracic region in a newborn, a
      gigantic patent ductus arteriosus was found. This vessel had a diameter as large
      as the pulmonary trunk and a longer length. The brachiocephalic a. and the left
      common carotid a. originated from the aortic arch in close proximity with each
      other. The descending aorta showed a dilatation at the junction of this large
      bored patent ductus arteriosus. We were unable to find any similar case in the
      published literature. Knowing that the anatomical variations of the great vessels
      may cause confusion during surgery or evaluation of CT and MRI scans, this rare
      case with a huge patent ductus arteriosus is presented.

PMID- 8983117
TI  - Synthesis and characterization of peptide adducts for use in monitoring human
      exposure to acrylonitrile and ethylene oxide.
AB  - Human exposure to ethylene oxide and acrylonitrile may be monitored by
      determination of the products that these electrophilic compounds form with the
      amino terminal of hemoglobin. The procedure involves a modified Edman
      degradation, using the reagent pentafluorophenyl isothiocyanate, which cleaves
      the adducted N-terminal amino acid from the protein chain as a substituted
      pentafluorophenyl thiohydantoin. This may then be quantitated using selected ion
      monitoring gas chromatography-mass spectrometry (GC-MS). To overcome problems
      arising from the lack of an ideal internal standard for this analysis, we have
      now synthesized adducts of ethylene oxide and acrylonitrile with the N-terminal
      tripeptide of the alpha-chain of human globin (Val-Leu-Ser). These adducts should
      behave analogously to the protein adduct in the Edman degradation. The adducts
      were characterized by nuclear magnetic resonance and fast atom bombardment and
      electrospray MS and tandem MS. Additionally, an analogous stable isotope-labeled
      standard was synthesized for the acrylonitrile adduct using a d8-labeled
      tripeptide. Quantitative calibration lines for analysis of the adducts have been
      established and the validity of the assays established by the detection of
      acrylonitrile adducts in the globin of acrylonitrile-exposed workers and of
      cigarette smokers.

PMID- 8983118
TI  - Effects of the antiepileptic drug valproic acid on the development of the axolotl
      (Ambystoma mexicanum): histological investigations.
AB  - In the amphibian Ambystoma mexicanum, valproic acid (VPA) causes retarded
      development and malformations including neural tube defects. Some of the observed
      abnormalities resemble exencephaly. We present the light microscopic
      characteristics of VPA-induced effects on the developing central nervous system
      (CNS) as well as on other developing tissues of this species. To induce
      malformations, various concentrations of VPA were applied to embryos from
      blastula stage on, either as 24-h pulse or as continuous exposure. In treated
      embryos the abnormal development of the CNS was indicated by retarded neurulation
      and disturbed closure of the neural folds. Furthermore, the neural epithelium was
      disorganized and its cells were less elongated than normal. Two ventricle lumina
      of various shapes arose in the neural tube and the neural epithelium extended
      laterally, whereas in the control animals the neural tube was small and overlaid
      the notochord only. In treated embryos intercellular spaces in neural epithelium
      as well as in connective tissue were enlarged and cell adhesion seemed disturbed
      in both tissues. The notochord underlying the neural plate appeared to be
      normally organized but oversized somites appeared, which periodically filled the
      space between notochord and notoplate. VPA also affected neural crest cells.
      Additional effects occurring were edema and liver damage. A high concentration of
      VPA even stopped development in early gastrulation. Characteristics of induced
      effects indicate an interaction between the drug and components of the
      extracellular matrix and the cytoskeleton.

PMID- 8983119
TI  - Dose-response relationship of teratogenicity and prenatal-toxic risk estimation
      of 6-mercaptopurine riboside in mice.
AB  - 6-Mercaptopurine riboside (6-MPr) is used as a cytostatic chemotherapeutic. The
      teratogenic potential in rodents has been well known for several decades. In this
      study, the teratogenic risk of low doses of 6-MPr in NMRI mice was estimated
      based on a dose-response study. The effective doses corresponding to the
      incidences of 5%, 1%, and 0.1% were calculated using the probit and Weibull
      model. The evaluation was performed on the basis of both the fetus and the litter
      by evaluating the variable all gross structural abnormalities. From these
      experiments, benchmark doses were obtained which were used in low-dose risk
      assessment to define a reference dose. Depending on the biometrical model and the
      statistical unit used, values between 1.9 and 5.2 mg/kg (benchmark ED1) and 3.8
      and 6.7 mg/kg (benchmark ED5) were obtained. These values were compared to the no
      observed adverse effect level (NOAEL) which was determined experimentally. The
      NOAEL was found to be 5 mg/kg, which is quite similar to the ED5 benchmark doses.

PMID- 8983121
TI  - A global view on the role of monocytes and platelets in atherogenesis.

PMID- 8983120
TI  - Testicular development and fertility of mice treated prenatally with N-nitroso-N
      ethylurea at various gestational stages.
AB  - N-nitroso-N-ethylurea (ENU) was injected intraperitoneally (i.p.) into ICR female
      mice at 50 mg/kg on day 8, 10, 12, or 16 of gestation (plug day = day 0). Male
      newborns treated prenatally with ENU were obtained. Body and testes weights of
      males were measured on postnatal days 4, 12, and 21 and at 12 weeks of age, as
      well as histopathological observation of their testes. The treated males were
      mated at 10 weeks to untreated females of the same strain. Subsequently, the
      plasma testosterone concentration in each group was determined by enzyme
      immunoassay. Body weight on postnatal day 4 in the group treated on day 16 of
      gestation was significantly lower compared to that of the control group. On
      postnatal day 21 and at 12 weeks of age, body weight was significantly lower in
      all groups treated with ENU compared to that of the control group. Among the
      embryonic stages tested, embryonic day 10 is the most susceptible to ENU insult
      with respect to the postnatal development of testes and epididymides, when judged
      by the relative weight at 12 weeks of age. The fertility of the male offspring
      was drastically impaired by the prenatal ENU treatment on embryonic day 10,
      followed by day 12, while the fertility of male offspring treated on embryonic
      days 8 and 16 was not affected. Histopathological sections of testes of male
      offspring treated with ENU on embryonic day 10 resulted in the most severe
      changes in the seminiferous tubules. The plasma testosterone concentration was
      drastically lower in male offspring treated on embryonic day 10 compared to the
      control level. These results demonstrate that the impaired fertility of the ENU
      affected mice was the result of paucity of germ cells and that the critical
      period in the male mouse fetus with respect to the disturbance of postnatal
      testicular development and fertility was around embryonic day 10, which is the
      period of primordial germ cell migration.

PMID- 8983123
TI  - Proteolytic activation of a putative receptor leading to vasoconstriction and
      platelet aggregation.
AB  - Submandibular enzymatic vasoconstrictor (SEV), a member of the kallikrein family
      of enzymes, elicits biological effects by a proteolytically mediated mechanism.
      We studied 1) whether SEV is able to aggregate platelets and 2) whether SEV may
      activate a receptor other than the cloned thrombin receptor. SEV (10(-8)M)
      aggregated platelets, released ATP and increased intracellular Ca2+. Elastase
      treatment rendered human platelets unresponsive to SEV and thrombin (TH), but not
      to cathepsin G. In desensitization experiments performed with gamma-TH, after two
      successive additions of approximately 50 nM gamma-TH, a third dose elicited 15.8
      +/- 3.4% of the initial response (n = 4), but platelets responded to
      approximately 20 nM SEV by 33.8 +/- 7.2% of control (p < 0.03 vs last response to
      gamma-TH). After desensitization to SEV (n = 4), the response to a third dose was
      4 +/- 1.3% of control, but gamma-TH still induced 37.7 +/- 12.4% aggregation (p <
      0.02 vs last response to SEV). Incubation of washed rabbit platelets with alpha
      TH digested with elastase (10(-10) M TH added to 7 micrograms/ml elastase for 1
      min) rendered them unresponsive to additional challenges with TH, but they still
      responded to an equipotent dose of SEV (2.7 x 10(-9) M) by 86 +/- 48% of control.
      In isolated rabbit aortic rings contracted with 10(-6) M norepinephrine (NE) to
      42 +/- 3% of maximum. SEV (2.8 x 10(-8) M) caused further contraction to 87 +/-
      4%. In contrast, alpha-TH (1.6 x 10(-7) M) tended to relax both NE- and SEV
      contracted rings by 14 +/- 2 and 16.2 +/- 2%, respectively (n = 3 each). We
      concluded that part of the platelet-aggregating effect of SEV may be mediated by
      activation of a receptor(s) different from that of TH.

PMID- 8983122
TI  - Influence of ionized calcium on thrombin-induced down regulation of GPIb/IX
      receptors on human platelets.
AB  - The influence of ionized calcium on the down-regulation of GPIb/IX receptors on
      human platelets was evaluated by flow cytometry using monoclonal antibodies.
      Addition of EDTA alone to a washed platelet suspension did not cause decreased
      monoclonal antibody binding to the cells. However, introduction of thrombin to
      the washed platelets containing EDTA resulted in a marked decrease in binding of
      monoclonal antibodies to the GPIb/IX receptors. If calcium at 1-3 mmol/L was
      added to buffered platelets instead of EDTA before thrombin, down-regulation was
      prevented or significantly reduced. Restoring calcium to EDTA platelets after the
      thrombin-stimulated down-regulation had been in progress for 1-3 minutes caused
      reversal of decreased antibody binding by GPIb/IX to near resting levels. Results
      demonstrate that extracellular calcium is a major factor regulating thrombin
      induced down-regulation.

PMID- 8983125
TI  - Intralipid rapidly attenuates the agonist-induced activation of rat platelets in
      vitro.
AB  - This study examines the uptake of Intralipid by rat platelets and the effect of
      Intralipid on platelet activation and platelet lipid composition in vitro. 3H
      cholesteryl hexadecyl ether labeled Intralipid (3H-Intralipid) was incubated with
      rat platelets for up to 4 hours. A significant uptake of 3H-Intralipid occurred
      as indicated by the increase of 3H in platelets with time. Addition of unlabelled
      Intralipid or chyle chylomicrons decreased the uptake of labeled Intralipid by
      the platelets, whereas Intralipid had less effect on the uptake of 14C linoleic
      acid labeled chylomicrons. Incubation of rat platelets with Intralipid caused a
      dose dependent inhibition of ADP, collagen and thrombin induced platelet
      aggregation and serotonin release. Both an attenuated response and a reduction of
      platelet cholesterol contents was seen within 10 minutes. Intralipid thus causes
      a rapid, dose- dependent inhibition of agonist-induced activation of rat
      platelets in vitro. This inhibition is linked to a loss of cholesterol and to an
      uptake of Intralipid particles by the platelets.

PMID- 8983124
TI  - The antithrombotic effect of synthetic low molecular weight human factor Xa
      inhibitor, DX-9065a, on He-Ne laser-induced thrombosis in rat mesenteric
      microvessels.
AB  - The effect of a synthetic low molecular weight factor Xa (FXa) inhibitor,
      DX9065a, on thrombosis in vivo were examined in a rat animal model using a Helium
      Neon (He-Ne) laser method. DX-9065a administered either intravenously or orally
      promoted anti factor Xa activity in a dose dependent manner. Anti Xa activity was
      maximal immediately after intravenous injection and persisted for approximately
      30 minutes. Inhibitory activity was maximal 15-30 minutes after oral
      administration and persisted for approximately 90 minutes. Similarly DX-9065a
      inhibited platelet-rich thrombosis formation in mesenteric arterioles and
      venules. In these instances inhibition was relatively transient after intravenous
      injection (10-20 minutes), but persisted for more than 3 hours after oral
      administration. The minimum effective doses of DX-9065a given intravenously and
      orally were 3.89 mg/kg and 25.9 mg/kg, respectively. The results confirmed that
      DX-9065a selectively modulates thrombotic mechanisms, and suggest that
      development of this synthetic FXa antagonist could constitute an effective
      intravenous and oral antithrombotic agent.

PMID- 8983126
TI  - Endothelial markers in diabetes mellitus.
AB  - In this study we examined 22 NIDDM patients without vascular complications and 17
      age-matched healthy blood donors. Von Willebrand factor (vWF) levels were
      significantly increased in NIDDM patients compared to healthy blood donors (1.33
      +/- 0.39 vs 1.01 +/- 0.27 IU/ml p = 0.006), while thrombomodulin (TM) levels were
      similar in the both groups. vWF levels correlated with calcium dependent
      secretion parameters such as C-peptide (r = 0.680, p < 0.001) and PF4 (r = 0.613,
      p < 0.01) and did not correlate with calcium-independent markers of endothelial
      injury such as TM (r = 0.287, p = 0.196) and TFPI (r = 0.296, p = 0.181).
      Therefore it seems that increased levels of Cai-dependent endothelial and
      platelet activation markers may precede the signs of endothelial damage. This
      hypothesis requires further research.

PMID- 8983127
TI  - Determination of the anti-factor Xa activity of the synthetic pentasaccharide SR
      90107A/ORG 31540 and of two structural analogues.
AB  - The anti-factor Xa activity of the synthetic pentasaccharide SR 90107A/ORG 31540
      was assayed by a chromogenic method at pH 8.4 and pH 7.35, comparatively to the
      4th International Heparin Standard (IHS) or to the Ist International Low
      Molecular Weight Heparin Standard (LMWHS). At pH 8.4, SR 90107A/ORG 31540 was
      found to have a specific anti-factor Xa activity of 639 +/- 14 and 659 +/- 19
      IU/mg (mean +/- sem, n = 6) when assayed in comparison with the 4th ISH and the
      Ist LMWHS respectively. At pH 7.35, the corresponding figures were 864 +/- 6 and
      1160 +/- 51 IU/mg (mean +/- sem, n = 6) respectively. The dissociation constants
      of the ATIII-pentasaccharide complex formed by SR 90107A/ORG 31540 and by two
      close analogues: SR 80327A and SR 80027A in the presence of purified human ATIII
      were found to be 41 +/- 8, 96 +/- 1 and 3 +/- 1.4 nM (mean +/- sem, n = 3)
      respectively. For the three compounds, the pseudo-first order molar catalytic
      constants for factor Xa inactivation by the ATIII-pentasaccharide complex were
      shown to be statistically comparable, in the range of 7-8 x 10(7) min-1 per mole.
      It is concluded that the differences in specific anti-factor Xa activities
      between SR 90107A/ORG 31540 and its synthetic chemical analogues can be
      attributed to variations of the dissociation constants whereas the catalytic
      constants for factor Xa inactivation remain unchanged.

PMID- 8983128
TI  - Practicability of patient self-testing of oral anticoagulant therapy by the
      international normalized ratio (INR) using a portable whole blood monitor. A
      pilot investigation.
AB  - The prophylactic efficacy of long-term oral anticoagulant treatment (OAT) has
      been demonstrated in a number of clinical conditions with increased tendency to
      thromboembolism, and the number of individuals subjected to OAT in the
      industrialised world has increased substantially in recent years. Since this
      therapy requires considerable resources from both the health care system and the
      patients, the feasibility of patients' self-monitoring and self-management of OAT
      has been investigated (1,2,3). The anticipated advantages of this approach
      include improved convenience and compliance for the patient, who may increase his
      apprehension for managing the treatment. In addition, self-testing allows for
      more frequent control compared to the conventional out-patient approach.
      Importantly, a prerequisite for conceiving a safe and operational concept for
      patient self-management (PSM) is the availability of a portable INR monitoring
      system with an accuracy, precision, reproducibility, and long-term reliability
      comparable to standard coagulometric equipment. The purpose of the present study
      was to evaluate the feasibility of a commercially available INR-monitor.
      CoaguChek, for patient self-testing, through a step-wise investigation of the
      performance characteristics of the equipment in the laboratory, in command of the
      patient, and during self-testing and self-adjustment of treatment at home.
      Laboratory INR values were used as reference.

PMID- 8983129
TI  - Integrated control of tropical animal parasitoses.
AB  - In the past, the control of parasites of domestic animals has relied mainly on
      the use of drugs and pesticides. Although these compounds are still of great
      importance in the prevention and treatment of parasitic diseases, the accent has
      shifted in recent years to a more flexible approach, integrating various other
      control measures. The main reasons for this change are: development of resistance
      of the parasites against the compounds used; reduced development of new compounds
      to overcome resistance (increasingly stringent regulations on toxicity and
      residues, resulting in very high research and development costs, insufficient
      return for industry because of short life-span of new products due to resistance,
      and limited and poor markets for compounds against parasites in developing
      countries); increasing cost of new products for the user; problems associated
      with toxicity, environmental pollution and residues in animal products.
      Integrated parasite management makes use, where possible, of biological and
      mechanical control methods, of acquired and innate host resistance, and of
      genetical, ecological, sanitary and regulatory procedures, although chemical
      control can seldom be entirely abolished. Cost-effectiveness and sustainability
      in all respects are of primary importance.

PMID- 8983130
TI  - Perinatal mortality in lambs in southern Brazil.
AB  - Hypothermia and dystocia were found to be the most common causes of perinatal
      mortality in 8 commercial wool flocks in one region of southern Brazil. It was
      established that low birth weight and poor maternal instinct in the ewes
      predisposed to losses due to hypothermia but that there appeared to be no
      association with adverse weather conditions. Other factors possibly predisposing
      to losses are discussed.

PMID- 8983131
TI  - Herd monitoring in traditional cattle husbandry as a tool for productivity
      research and livestock development.
AB  - In the Western Province of Zambia, a productivity study was carried out in
      traditionally managed cattle herds. The organisational design of the study and
      the procedures involved in the management of the data are described. Some
      possibilities of use of the data are discussed.

PMID- 8983132
TI  - Integrated tick and tick-borne disease control trials in crossbred dairy cattle
      in Malawi.
AB  - Crossbred dairy heifers on a farm in an East Coast fever (ECF) endemic area in
      Malawi were immunised against Theileria parva, Anaplasma spp., Babesia bigemina,
      Babesia bovis and Cowdria ruminantium. They were treated at infrequent intervals
      with chlorfenvinphos to limit infestation with adult ticks, without providing
      complete tick control. In one trial, which tested a threshold dipping regimen, 20
      heifers were dipped only once in 6 months to control a flush of Boophilus
      microplus. Unimmunised controls showed serological evidence of exposure to T.
      parva and B. bigemina, and one died of ECF, but there were no incidents of tick
      borne disease in the immunised group. In a second trial, which tested a strategic
      dipping regimen, 107 animals were dipped 9 times over a 6 month period. Despite
      heavy challenge by B. bovis and moderate challenge by B. bigemina and Anaplasma
      spp. demonstrated serologically, there was only a single clinical case of
      babesiosis. The observations provide encouragement for the introduction of
      integrated tick and tick-borne disease control programmes in improved cattle in
      ECF endemic areas.

PMID- 8983133
TI  - Theileria annulata schizonts found in calf kidney cell culture.
AB  - Mononuclear cells infected with Theileria annulata schizonts were isolated at 4
      different times from monolayer cultures of primary kidney cells derived from
      apparently healthy, 2 to 6 weeks old zebu calves. The presence of such an
      organism could interfere with the manufacturing procedure of rinderpest tissue
      culture vaccine if it is to be carried out in calf kidney cell culture.

PMID- 8983134
TI  - Estimation of antibodies to Newcastle disease virus in tears.
AB  - Micro-haemagglutination inhibition tests (Micro-HI) were used to measure the
      level of maternal IgG in the tears of chicks and also to measure the levels of HI
      antibodies in the tears and serum after vaccination with "F" strain of Newcastle
      disease virus (NDV) and in the face of an outbreak of Newcastle disease. There
      was a 1.4 fold difference between the maternal IgG concentration in the serum and
      tears. The ratio of serum IgG to lachrymal IgG after maternal transfer was 4 to
      5:1 on day 4 to 9 and decreased to 2.6:1 on day 12 post-hatch. The intra-ocular
      vaccination of chicks with "F" strain of NDV resulted in the highest titre of HI
      antibodies in the tears though there was no significant difference in the
      response of chicks vaccinated through intranasal, oral and intravenous routes. In
      the face of an ND outbreak, the level of HI antibodies in the tears during the
      acute phase was very high and persisted at the same level for 14 days.

PMID- 8983135
TI  - Performance of draught cattle in communal farming areas in Zimbabwe after dry
      season supplementation.
AB  - Sixty-four pairs of oxen owned by smallholders were randomly allocated to one of
      3 supplementary treatments offered at one kg per head per day from July to
      October or to a control where no supplement was offered. The supplements were
      maize stover plus silverleaf hay (2:1 w/w), urea-treated maize stover (50 g
      urea/kg stover) and plain maize stover. Animals fed plain maize stover or no
      supplement lost weight (6 to 7% of initial weight), whilst those fed the other 2
      supplements maintained their liveweights. Supplementation reduced time spent on
      feeding activities by 10 per cent. Animals fed on urea-treated maize stover or
      maize stover plus silverleaf hay ploughed at speeds that were 29% faster than
      oxen on the other treatments and covered 45% more area. Blood parameters
      indicated a general deficiency of nitrogen intake throughout the dry season. It
      was concluded that supplements of good quality have the potential to improve the
      working ability of communal area oxen.

PMID- 8983136
TI  - Effects of feeding cattle manure on growth performance and carcass
      characteristics of large white pigs.
AB  - Thirty-six weaner Large White piglets were randomly assigned to 3 replicates of 3
      treatments to determine the effects of feeding 0, 10 or 20% of cattle manure in
      partial replacement of ground maize in the diet. The trial lasted 15 weeks. Feed
      efficiency was not significantly affected. However, pigs fed on the control diet
      consumed significantly more feed than pigs on the experimental diets containing
      cattle manure, and although their higher daily weight gain was not statistically
      significant, at the end of the trial they were significantly heavier (P < 0.05)
      than those fed the diet containing 20% cattle manure. Carcasses from pigs fed on
      the diets containing cattle manure were leaner than pigs fed on the control diet.

PMID- 8983137
TI  - Linguatula serrata (Frolich 1789) nymphs in lungs of goats in iran.

PMID- 8983138
TI  - Actinobacillus lignieresi infection in camels on the Sokoto plains, Nigeria.

PMID- 8983139
TI  - Traumatic reticulopericarditis caused by a non-metallic object.

PMID- 8983144
TI  - Toxoplasma gondii: experimental infection in cats vaccinated with 60Co-irradiated
      tachyzoites.
AB  - The effects of 60Co-irradiation on the viability and immunogenicity of RH and
      Beverley strains of Toxoplasma gondii was examined. While 60Co-irradiated
      tachyzoites retained invasive activity in mouse embryonal cells and sustained
      antigenicity in mouse peritoneal macrophages, the parasites did not develop in
      host cells. Vaccination of mice with 60Co-irradiated tachyzoites of either RH or
      Beverley strains induced resistance to challenge with a highly virulent strain
      (RH strain). Vaccination of kittens with 60Co-irradiated tachyzoites of the
      Beverley strain partially prevented oocyst shedding when challenged with cysts
      (bradyzoites) from the Beverley strain. But kittens vaccinated with 60Co
      irradiated or fixed tachyzoites of the RH strain shed oocysts when challenged
      with cysts (bradyzoites) from the Beverley strain. These results suggest that the
      development of protective immunity in feline toxoplasmosis seems to be strain
      and/or stage-specific.

PMID- 8983146
TI  - Epidemiology of tropical theileriosis (Theileria annulata infection of cattle) in
      an endemic region of Tunisia: characterisation of endemicity states.
AB  - A serological survey on tropical theileriosis was conducted on a sample of 54
      farms in a region within the semi-arid bioclimatic zone of Tunisia. Screening of
      cattle sera at a dilution of 1/160 using the indirect immunofluorescent antibody
      test with the schizont antigen of Theileria annulata, revealed the presence of
      animals with positive sera in 92.15% of the sampled farms. The exposure of calves
      to infection in the first season was shown to be significantly lower than in
      older cattle. Three endemic situations were identified based on the serological
      profiles of herds and the incidence and age distribution of disease cases.
      Endemic stability was observed in farms showing a sero-prevalence of 100% in
      cattle of four theileriosis seasons or more and by the incidence of the highest
      disease levels in cattle at their second and third theileriosis season. High
      endemic instability was identified on the basis of low sero-prevalence rates and
      the occurrence of the highest disease incidence in cattle at fourth theileriosis
      season or more.

PMID- 8983145
TI  - Production of a recombinant fusion protein of Sarcocystis tenella and evaluation
      of its diagnostic potential in an ELISA.
AB  - We have isolated a cDNA clone encoding an antigenic polypeptide of Sarcocystis
      tenella by screening a cystozoite-derived cDNA library in lambda gt11 with
      antibodies from sheep infected experimentally with S. tenella. This clone, termed
      STC29, was subcloned and expressed in the vector pGEX-3X as a soluble fusion
      protein with glutathione S-transferase having an apparent molecular mass of 46
      kDa. Antibody raised against the recombinant fusion protein recognized a native
      polypeptide of 25 kDa in cystozoites of S. tenella. In an ELISA with sera from
      experimentally infected sheep, the recombinant STC29 antigen could differentiate
      infections with S. tenella from those with Sarcocystis arieticanis or Toxoplasma
      gondii. Hence, the research described here reports the identification of the
      first recombinant S. tenella antigen that may be useful for standardization of a
      serological test for the diagnosis of S.tenella infections in sheep.

PMID- 8983147
TI  - Eimeria magna Perard, 1925: study of the endogenous development of parental and
      precocious strains.
AB  - The endogenous development of a parental strain of E. magna and its deriving
      precocious line was studied after inoculation of coccidia-free rabbits with
      oocysts or sporocysts directly into the duodenum and using electron microscopy.
      Four meront generations could be observed mainly in the jejunum and ileum for the
      parent strain. The first merogony began 24 h post-inoculation (h p.i.). and
      meronts were matured about 48 h p.i. The second and the third generation were
      complete at 66 and 84 h p.i. respectively. Thus, each generation needs
      approximately 16-20 h for maturation. The fourth generation appeared 102 h p.i.
      and the young gamonts were present 120 h p.i. As in the other rabbit Eimeria, two
      types of meronts were described: A and B. The morphology of all endogenous stages
      of the precocious line was similar but refractile bodies were absent in the first
      generation merozoites and the fourth generation meront was lacking.

PMID- 8983148
TI  - Effects of initial litter contamination level with Eimeria acervulina on
      population dynamics and production characteristics in broilers.
AB  - The present experiment was done to obtain experimental evidence supporting the
      existence of an optimal initial contamination level of Eimeria acervulina with
      respect to broiler productivity, as suggested by simulation model outcomes. Three
      levels of initial (on Day 3) contamination of the litter were applied (low,
      intermediate and high). The peak of oocyst excretion during the flock cycle (grow
      out) (Days 0-36) depended on the initial contamination level. Oocysts peaked at
      Day 15, 22 and 33 for the high, intermediate and low contamination level,
      respectively. Antibody titres and plasma carotenoid contents were not
      significantly affected by contamination levels. Average body weight at the end of
      the flock cycle (Day 36) and average daily body weight gain were significantly
      higher at the intermediate contamination level compared with the low and high
      contamination levels. Average body weight at Day 36 was 1681 g, 1712 g and 1674 g
      for the low, intermediate and high contamination level, respectively. Average
      daily weight gain was 45.7 g, 46.5 g and 45.5 g for the low, intermediate and
      high contamination level, respectively. Thus, the data from this experiment
      support the existence of an optimum initial contamination level for E. acervulina
      with respect to performance results.

PMID- 8983149
TI  - Cattle infestation by Hyalomma ticks and prevalence of Theileria in H. detritum
      species in Tunisia.
AB  - Seventy-four cattle, from three farms endemic for tropical theileriosis in the
      north of Tunisia, were studied for tick populations from June 1991 to June 1992.
      Ticks were removed from cattle twice a month in the summer and every month the
      rest of the year. They were identified and assessed for Theileria infection. A
      total of 5083 Hyalomma adult ticks were collected and the major species found was
      H. detritum (84.3%). The activity of this species is limited between June and
      August with a peak in numbers observed at the end of June and the beginning of
      July. Amongst the 2356 Hyalomma ticks dissected, no evidence of salivary gland
      infection was found in either H. m. marginatum or H. a. excavatum. However, 12.4%
      (277/2230) of H. d. detritum dissected ticks were infected with Theileria species
      and amongst these, 62% had one to two sporoblasts in their salivary glands (range
      1-91). The prevalence, but not the intensity, of infection was greater in females
      than in male ticks, and the cases of tropical theileriosis followed the peak of
      infected females. This suggests that female ticks have a more important role in
      theileriosis transmission than male ticks. A significantly lower number of adult
      H. detritum were collected from calves, at their first tick season, than from
      adult cattle. Finally, this study showed that the infestation level of cattle by
      H. d. detritum and the prevalence of Theileria-infection in these cattle varied
      between the three farms studied.

PMID- 8983150
TI  - Immunological responses in the mouse host to a cloned antigen of Taenia
      crassiceps.
AB  - Adult female Swiss-Webster mice were immunized either intraperitoneally (IP) or
      subcutaneously (SQ) with cyst fluid or a genetically engineered fusion protein,
      Taenia crassiceps antigen 2-maltose binding protein (TCA2-MBP) from Taenia
      crassiceps metacestodes, or with live, non-budding cysts SQ, and then challenged
      IP with T. crassiceps metacestodes and necropsied 9 weeks later. Numbers of
      peripheral blood eosinophils were increased after IP immunization, but were not
      increased after SQ immunization or with SQ cysts given before the challenge
      infection. Eosinophil numbers gradually decreased over the course of the
      experiment, and were not found in increased numbers in the blood or peritoneal
      cavity at necropsy. Antigen-specific antibody responses were seen at day 14 or 28
      in IP and SQ immunized groups: IgG1 and IgG3 isotypes continued to increase over
      the course of the experiment. A significant protective response was induced by
      immunization with the cyst fluid (15 +/- 4, X +/- SE recovered larvae) or the
      TCA2-MBP (22 +/- 12) given IP, but not SQ (122 +/- 36; 207 +/- 53, respectively)
      as measured by the numbers of larvae recovered at necropsy. Live cysts given SQ
      resulted in reduced numbers of cysts in the peritoneal cavity (188 +/- 66), but
      was not as effective as cyst fluid or TCA2-MBP given IP. Locally (IP) induced
      immune responses may be involved in the development of the protective response to
      a challenge infection with T. crassiceps metacestodes.

PMID- 8983152
TI  - Control of Filaroides hirthi infections in Beagle dogs by ivermectin.
AB  - The efficacy of ivermectin against Filaroides hirthi was evaluated in a series of
      three trials using Beagle dogs of a breeding colony known to be endemically
      infected with this lungworm. Ivermectin was subcutaneously given at a dosage of 1
      mg kg-1 bodyweight once to 40 (group A) or, at a one week interval, twice to 32
      dogs (group B) 14-15 weeks prior to necropsy; another 40 dogs (group C) remained
      untreated. All animals were necropsied and lungs were digested using the pepsin
      hydrochloride method and qualitatively examined for Filaroides spp. stages. A
      44.8% and 74.1% reduction of the prevalence of lungworm infection as well as a
      87.5% and 94.8% reduction of the proportion of dogs harbouring first-stage
      Filaroides spp. larvae were found in groups A and B, respectively, as compared to
      group C. These results suggest that repeated treatments of breeding dogs with
      ivermectin might reduce the transmission of F. hirthi infection to their
      offspring.

PMID- 8983151
TI  - Susceptibility of Suffolk and Gulf Coast Native suckling lambs to naturally
      acquired strongylate nematode infection.
AB  - Three trials compared responses to naturally-acquired strongylate nematode
      infection between suckling Suffolk and Gulf Coast Native (Native) lambs which
      grazed together. In Trial 1 (1992), infection in 14 lambs of each breed was
      monitored from birth to 12 weeks of age using fecal egg count (FEC) and blood
      packed cell volume (PCV). In Trial 2 (1993), two age-matched lambs of each breed
      were sacrificed at seven and ten weeks of age to estimate nematode burdens. In
      Trial 3 (1994), infection in 18 lambs of each breed was monitored (FEC, PCV,
      white blood cell count, differential leukocyte count, and anti-Haemonchus
      contortus immunoglobulin level) from birth to 8 weeks of age, at which time six
      age-matched lambs of each breed were sacrificed to estimate nematode burdens. The
      remaining 24 lambs were monitored until 12 weeks of age. In both Trials 1 and 3,
      infection in Native lambs peaked and then declined between 6-10 weeks of age.
      Infection in Suffolk lambs continued to increase as evidenced by increasing FEC
      with concomitant reduction in PCV, higher morbidity and mortality (Trial 1), and
      number of anthelmintic treatments required (Trial 3). In Trials 2 and 3, the
      principal nematode found at necropsy was H. contortus, and infection level was
      consistently lower (> 64%) in Native compared with Suffolk lambs. In Trial 3,
      there was no difference between breeds for WBC, any leukocyte type, or anti-H.
      contortus immunoglobulin level. These results demonstrated that suckling Native
      lambs developed resistance to H. contortus infection during their first exposure
      to infection at an age when they are considered immune incompetent and
      colostrally transferred anti-H. contortus immunoglobulin did not appear to be
      involved in the resistance.

PMID- 8983153
TI  - Growth and cuticular synthesis in Ascaris suum larvae during development from
      third to fourth stage in vitro.
AB  - Growth, molting and cuticular protein synthesis were determined during the
      development of Ascaris suum grown in vitro from the third (L3) to the fourth (L4)
      larval stage. The larvae remained highly viable (90%) and 70% reached the L4 by 7
      days in culture (DIC). Analysis of growth and development indicated that ecdysis
      was asynchronous. The synthesis of noncuticular and cuticular proteins was
      monitored using 35S-methionine as a metabolic label. Synthesis of noncuticular,
      cuticular and collagenous cuticular proteins increased in a constant manner,
      reaching maximal values at about 6 DIC. Synthesis of noncollagenous cuticular
      proteins (cuticlin) remained relatively constant during most of the culture
      period, but increased from 6 to 7 DIC. The increase in cuticlin synthesis and the
      corresponding decrease in cuticular collagen synthesis noted at 7 DIC might
      represent the synthesis of the outer portions of the adult cuticle in preparation
      for the fourth molt. The results of this study suggest that this in vitro
      development system for A. suum, while not suitable to study events regulating the
      precise timing of molting and cuticular synthesis, might be useful for the
      analysis of potential growth regulators.

PMID- 8983154
TI  - Seasonal pattern of inhibition of Ostertagia ostertagi in calves in northeast
      Mississippi.
AB  - The composition of, and seasonal changes in, populations of gastrointestinal
      parasites of calves in northeast Mississippi were determined for 10 months post
      weaning. After weaning on 15 October, 20 mixed breed beef steers were grazed
      together on a 4 ha fescue/bermudagrass pasture. From November through August of
      the following year, two of the calves were removed each month for necropsy and
      counting of gastrointestinal nematodes. Eight species of worms were found:
      Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Bunostomum
      phlebotomum, Cooperia spp., Trichostrongylus colubriformis, Oesophagostomum spp.,
      and Trichuris ovis. During all months, Ostertagia ostertagi and Cooperia spp.
      combined comprised at least 89% of gastrointestinal nematode burdens. Cooperia
      spp. represented 92.6% of the total worm burden of calves in November but
      declined to about 56% in January and February. From March through August,
      Ostertagia ostertagi comprised at least 79% of the worms from calves. Numbers of
      inhibited Ostertagia ostertagi increased markedly from February to March and
      remained at high levels prior to resumption of development in August. The
      proportion of Trichostrongylus axei remained about 4% throughout the year, but
      the highest numbers were recorded in the summer months. Other species were minor
      components of the worm population. These data indicate that with respect to
      Ostertagia ostertagi, northeast Mississippi can be considered a summer inhibition
      zone.

PMID- 8983155
TI  - Bovine humoral immune responses to Haemonchus placei excretory secretory
      antigens.
AB  - The immune response of calves against excretory secretory (ES) products of adult
      Haemonchus placei was studied. The ES products of adult H. placei comprise at
      least ten polypeptides with molecular weights ranging from 10 to over 100 kDa. A
      primary infection of calves with H. placei did not result in a marked elevation
      of IgG serum antibodies reactive to ES antigens as demonstrated by ELISA.
      Immunoblotting experiments revealed that sera of primary infected calves
      recognised a 50 kDa antigen in most cases. An increase in the level of serum IgG
      antibodies was observed after trickle infections. The secondary immune response
      coincided with the recognition of a group of three ES antigens of around 50-55
      kDa and one protein with a molecular weight of 24 kDa.

PMID- 8983156
TI  - Seasonal transmission of Fasciola hepatica in Montana, USA, with detection of
      infected intermediate hosts using a DNA-based assay.
AB  - A cashmere goat ranch in the Beaverhead Valley, southwest Montana, USA reported
      acute fasciolosis in March 1992. The ranch was used as a study site to gather
      seasonal transmission data for the liver fluke, Fasciola hepatica. Testing of
      snails for infection with a nucleic acid-based assay, and use of tracer sheep at
      the site has shown the seasonal transmission of the parasite is only in late
      autumn. The snail responsible for transmission was identified as Lymnaea
      modicella although another known intermediate host species, Lymnaea bulimoides,
      was found in one collection at the study site. Tracer sheep used over a 12-month
      period became infected with F. hepatica while on pasture during a period between
      September 10 and November 12, 1993. During the 28 months of study, 3072
      individual lymnaeid snails were tested for infection. One sample of L. modicella
      containing 25 snails, collected in August 1994 contained liver fluke ribosomal
      RNA.

PMID- 8983157
TI  - Efficacy of closantel against Fasciola hepatica in Korean native goats.
AB  - Closantel (Flukiver), a salicylanilide antiparasitic compound, was tested in
      Korean native goats infected with Fasciola hepatica. The goats were administered
      closantel once orally at a dose of 10 mg/kg body weight. Efficacy was monitored
      weekly by fecal examination of all infected animals starting the second week post
      treatment and continuing for 3 weeks. Closantel elicited 80.3, 97.8 and 92.7%
      efficacy in goats with naturally-acquired fasciolosis at the second, third and
      fourth week post-treatment, respectively. It elicited a 100% efficacy in goats
      experimentally infected with F. hepatica metacercariae and treated at 18 weeks
      post-infection.

PMID- 8983158
TI  - Rupture of femoral artery in a dog infected with Angiostrongylus vasorum.
AB  - A crossbred bitch, infected with Angiostrongylus vasorum, died on the 46th day
      post infection. Post mortem findings showed that the rupture of the femoral
      artery was the cause of death. A. vasorum was present in the femoral artery.

PMID- 8983159
TI  - Synthesis of diastereomeric mixtures of 5'-C-hydroxymethylthymidine and
      introduction of a novel class of C-hydroxymethyl functionalised
      oligodeoxynucleotides.
AB  - Novel 5'-C-hydroxymethyl substituted derivatives of thymidine have been prepared
      by dihydroxylation of the 5'C-methylene nucleoside 1. Osmium tetraoxide catalysed
      dihydroxylation of 1 afforded a 3:2 epimeric mixture of diols 2, whereas
      asymmetric dihydroxylation using AD-mix-alpha and AD-mix-beta resulted in
      mixtures 3 and 4 of the two epimeric diols, both enriched with the same
      diastereomer. Nucleosides 2 were transformed into phosphoramidites 8 which were
      used for solid phase synthesis of oligodeoxynucleotides (ODNs) containing 5'-C
      (hydroxymethyl) functionalised thymidine monomers. This novel class of C
      hydroxymethyl modified ODN-analogues exhibited promising affinity towards both
      complementary DNA and RNA as well as resistance towards 3'-exonucleolytic
      degradation.

PMID- 8983160
TI  - A kinetic mechanism for nicotinic acetylcholine receptors based on multiple
      allosteric transitions.
AB  - Nicotinic acetylcholine receptors are transmembrane oligomeric proteins that
      mediate interconversions between open and closed channel states under the control
      of neurotransmitters. Fast in vitro chemical kinetics and in vivo
      electrophysiological recordings are consistent with the following multi-step
      scheme. Upon binding of agonists, receptor molecules in the closed but
      activatable resting state (the Basal state, B) undergo rapid transitions to
      states of higher affinities with either open channels (the Active state, A) or
      closed channels (the initial Inactivatable and fully Desensitized states, I and
      D). In order to represent the functional properties of such receptors, we have
      developed a kinetic model that links conformational interconversion rates to
      agonist binding and extends the general principles of the Monod-Wyman-Changeux
      model of allosteric transitions. The crucial assumption is that the linkage is
      controlled by the position of the interconversion transition states on a
      hypothetical linear reaction coordinate. Application of the model to the
      peripheral nicotine acetylcholine receptor (nAChR) accounts for the main
      properties of ligand-gating, including single-channel events, and several new
      relationships are predicted. Kinetic simulations reveal errors inherent in using
      the dose-response analysis, but justify its application under defined conditions.
      The model predicts that (in order to overcome the intrinsic stability of the B
      state and to produce the appropriate cooperativity) channel activation is driven
      by an A state with a Kd in the 50 nM range, hence some 140-fold stronger than the
      apparent affinity of the open state deduced previously. According to the model,
      recovery from the desensitized states may occur via rapid transit through the A
      state with minimal channel opening, thus without necessarily undergoing a
      distinct recovery pathway, as assumed in the standard 'cycle' model. Transitions
      to the desensitized states by low concentration 'pre-pulses' are predicted to
      occur without significant channel opening, but equilibrium values of IC50 can be
      obtained only with long pre-pulse times. Predictions are also made concerning
      allosteric effectors and their possible role in coincidence detection. In terms
      of future developments, the analysis presented here provides a physical basis for
      constructing more biologically realistic models of synaptic modulation that may
      be applied to artificial neural networks.

PMID- 8983162
TI  - From twitch to tetanus: performance of excitation dynamics optimized for a twitch
      in predicting tetanic muscle forces.
AB  - In models of the excitation of muscles it is often assumed that excitation during
      a tetanic contraction can be obtained by the linear summation of responses to
      individual stimuli from which the active state of the muscle is calculated. The
      purpose of this study was to investigate whether such a model adequately
      describes the process of excitation of muscle. Parameters describing the
      contraction dynamics of the muscle model used were derived from physiological and
      morphological measurements made on the gastrocnemius medialis muscle of three
      adult Wistar rats. Parameters pertaining to the excitation dynamics were
      optimized such that the muscle model correctly predicted force histories recorded
      during an isometric twitch. When a relationship between intracellular calcium and
      active state from literature on rat muscle was used, the muscle model was capable
      of generating force histories at stimulation frequencies of 20, 40, 60 and 80 Hz
      and other muscle-tendon complex lengths which closely matched those measured
      experimentally - albeit forces were underestimated slightly in all cases.
      Differences in responses to higher stimulation frequencies between animals could
      be traced back to differences in twitch dynamics between the animals and adequate
      predictions of muscle forces were obtained for all animals. These results suggest
      that the linear summation of responses to individual stimuli indeed gives an
      adequate description of the excitation of muscle.

PMID- 8983161
TI  - Nonlinearity in normal human EEG: cycles, temporal asymmetry, nonstationarity and
      randomness, not chaos.
AB  - Two-hour vigilance and sleep electroencephalogram (EEG) recordings from five
      healthy volunteers were analyzed using a method for identifying nonlinearity and
      chaos which combines the redundancy-linear redundancy approach with the surrogate
      data technique. A nonlinear component in the EEG was detected, however,
      inconsistent with the hypothesis of low-dimensional chaos. A possibility that a
      temporally asymmetric process may underlie or influence the EEG dynamics was
      indicated. A process that merges nonstationary nonlinear deterministic
      oscillations with randomness is proposed for an explanation of observed
      properties of the analyzed EEG signals. Taking these results into consideration,
      the use of dimensional and related chaos-based algorithms in quantitative EEG
      analysis is critically discussed.

PMID- 8983163
TI  - Electrical bursting and luminal calcium oscillation in excitable cell models.
AB  - It is shown in this paper that electrical bursting and the oscillations in the
      intracellular calcium concentration, [Ca2+]i, observed in excitable cells such as
      pancreatic beta-cells and R-15 cells of the mollusk Aplysia may be driven by a
      slow oscillation of the calcium concentration in the lumen of the endoplasmic
      reticulum, [Ca2+]lum. This hypothesis follows from the inclusion of the dynamic
      changes of [Ca2+]lum in the Chay bursting model. This extended model provides
      answers to some puzzling phenomena, such as why isolated single pancreatic beta
      cells burst with a low frequency while intact beta-cells in an islet burst with a
      much higher frequency. Verification of the model prediction that [Ca2+]lum is a
      primary oscillator which drives electrical bursting and [Ca2+]i oscillations in
      these cells awaits experimental testing. Experiments using fluorescent dyes such
      as mag-fura-2-AM or aequorin could provide relevant information.

PMID- 8983164
TI  - Pharmacokinetic considerations in the camel (Camelus dromedarius): a review.
AB  - In this article the pharmacokinetic profile of several antibacterial,
      antiparasitic and antiinflammatory agents in camels has been reviewed. The effect
      of dehydration on the kinetics of these drugs has also been discussed.

PMID- 8983165
TI  - TCDD, endrin and lindane induced oxidative stress in fetal and placental tissues
      of C57BL/6J and DBA/2J mice.
AB  - The abilities of TCDD, endrin and lindane to induce oxidative stress in fetal and
      placental tissues have been studied after the oral administration of these
      xenobiotics to pregnant C57BL/6J and DBA/2J mice. Production of superoxide anion,
      lipid peroxidation and DNA-single strand breaks (SSB) was determined in live
      fetal and placental tissues 48 hr after administration of single teratogenic
      doses of the compounds on day 12 of gestation. Oxidative stress and its
      biomarkers were also determined in livers of day 18 fetuses after administration
      on day 12 of gestation. TCDD given at doses of 30 and 60 micrograms/kg body
      weight to the C57BL/6J and DBA/2J mice, respectively, produced increases of 1.3
      2.7-fold in superoxide anion production, 1.6-1.9-fold in lipid peroxidation and
      2.1-4.4-fold in DNA-SSB. Endrin, given at a dose of 4.5 mg/kg body weight to
      C57BL/6J and DBA/2J mice, produced increases of 1.3-2.8-fold in superoxide
      production, 1.4-1.8-fold in lipid peroxidation and 1.4-4.7-fold in DNA-SSB.
      Lindane when given at a dose of 30 mg/kg body weight to C57BL/6J and DBA/2J mice
      produced increases of 1.6-3.0-fold in superoxide production, 1.3-2.1-fold in
      lipid peroxidation and 1.4-5.0-fold in DNA-SSB. The results suggest that
      superoxide production, lipid peroxidation and DNA-SSB in fetal and placental
      tissues may participate in the fetotoxic effects of TCDD and other
      polyhalogenated cyclic hydrocarbons, and that TCDD-induced oxidative damage in
      fetal and placental tissues is mediated at least in part by the Ah-receptor. The
      results also indicate that TCDD as an inducer of oxidative tissue damage in the
      embryos and placentas is approximately 150 and 1000 times more potent than endrin
      and lindane, respectively, in C57BL/6J mice, and 75 and 500 times more potent
      than endrin and lindane, respectively, in the DBA/2J mouse strain.

PMID- 8983166
TI  - Effects of breed and adipose depot location on responsiveness and sensitivity to
      adrenergic stimulation in ovine adipose tissue.
AB  - Karakul tail adipose tissue had the smallest adipocytes, and this tissue was also
      the least lipolytically responsive. However, lipolytic responsiveness did not
      vary with breed or depot when expressed per gram of tissue. Sensitivity to
      isoproterenol and epinephrine was higher in tissues of the Karakul than of the
      Outaouais breed of sheep. As well, there was evidence for alpha-antilipolytic
      action in Karakul but not Outaouais adipose tissue. The Karakul breed is a unique
      model for the study of adipocyte metabolism in that a wide range of adipocyte
      volumes exist within an individual, and the Karakul adipose tissue appears to be
      particularly sensitive to adrenergic regulation.

PMID- 8983167
TI  - Balance between opposite effects of short day stimulation and testicular steroid
      feedback inhibition on pituitary pulsatile LH release in male mink, Mustela
      vison.
AB  - This study explores changes in pituitary pulsatile Luteinizing Hormone (LH)
      secretion in intact and castrated male mink, either previously
      photogonadostimulated by short day treatment (LD 4:20), or maintained in a state
      of sexual quiescence by long day treatment (LD 20:4). Artificial photoperiodic
      treatment of intact mink significantly increases plasma LH level and pulse
      frequency, following transfer from inhibiting long-to stimulating short-days.
      This photoperiodic control mimics two important phases of the annual reproductive
      cycle: seasonal maximum gonadal activity and sexual quiescence. Furthermore,
      pulsatile secretion of LH is investigated 48 hours after castration. When mink
      castrated during long day treatment are compared against control intact mink, no
      change in their low LH secretion parameters are observed. This result indicates
      that gonadal steroids on long days are not suppressing LH secretion, which is
      controlled by photoperiodic inhibition alone. When mink are castrated at the
      onset of short day induced gonadal growth, mean plasma LH level and amplitude of
      LH pulses are increased over that found in stimulated intact mink. This result
      indicates that, during the phase of resumption of gonadal activity on short days,
      testicular steroid feedback partially controls the pituitary activity.

PMID- 8983168
TI  - A pharmacological study of cocaine activity in planaria.
AB  - Planaria has been proposed as a suitable research model in neurobiology because
      of its relatively simple organization. Dopaminergic agonists induce in this
      flatworm typical hyperkinesias that can be antagonized by dopaminergic blocking
      agents. The neurochemical basis of the effects of cocaine in vertebrates has not
      been fully elucidated, but the inhibition of catecholamine reuptake at a
      presynaptic level seems to play an important role. In this study we analyzed the
      involvement of the dopaminergic system in the mechanism of action of cocaine in
      planaria. The dose-related effects of cocaine on planaria motility and the
      response to cocaine treatment associated with the administration of specific D1
      or D2 dopamine agonists and antagonists were investigated. The effects of
      reuptake inhibitors on cocaine activity were also studied. Planaria specimens
      treated with low doses of cocaine become motionless, whereas high doses induce a
      typical behavioural response, identical to the response induced by specific D2
      agonists. This response is inhibited by a D2 selective blocking agent.
      Nomifensine, a specific dopamine reuptake inhibitor, induces a mixed D1/D2
      response. The results of these experiments are discussed, also in relation with
      the conservation of dopaminergic receptors during evolution.

PMID- 8983169
TI  - Effects of experimental dicrocoeliosis on oxidative drug metabolism in hamster
      liver.
AB  - The purpose of this investigation was to determine the effects of experimental
      dicrocoeliosis on the hepatic oxidative drug-metabolizing system in hamsters.
      Studies were carried out 80 and 120 days after infestation with an oral dose of
      40 metacercariae of Dicrocoelium dendriticum. The parasitic pathology was
      ascertained by detection of the fluke eggs in faeces, increased serum alanine
      aminotransferase and aspartate aminotransferase activities, and postmortem and
      histological findings. Cytochrome P-450 concentration, aniline hydroxylase
      activity and ethoxycoumarin O-deethylase activity were significantly decreased in
      both groups of infected animals. Aminopyrine N-demethylase activity and
      erythromycin N-demethylase activity were only reduced 120 days after infection.
      Effects on drug metabolizing enzymes were unrelated to changes in the physical
      state of the microsomal membrane, as assessed by measurement of fluorescence
      polarization. The results of this study indicate that the capacity of the liver
      for handling drugs and xenobiotics may be impaired as a consequence of
      dicrocoeliosis.

PMID- 8983170
TI  - Characterization of the beta 2 adrenoceptors of dog liver.
AB  - The beta-adrenoceptors present in dog liver were characterized by radioligand
      binding techniques. [3H]Dihydroalprenolol bound with high affinity (KD 0.9 nM) to
      a relatively low number of sites (approximately 68 fmol/mg protein) in partially
      purified dog liver plasma membranes. These sites were characterized by binding
      competition; the orders of affinity were: (a) for agonists: (-)isoproterenol > or
      = salbutamol > epinephrine > or = terbutaline > norepinephrine > (+)isoproterenol
      and (b) for antagonists: propranolol > ICI 118551 >> metoprolol >> atenolol.
      These data indicate that dog liver expresses beta-adrenoceptors of the beta2
      subtype.

PMID- 8983171
TI  - Specific binding sites for atrial natriuretic peptide in the freshwater turtle,
      Amyda japonica.
AB  - Specific binding sites for atrial natriuretic peptide (ANP) were investigated by
      in vitro autoradiographic techniques in various tissues of the freshwater turtle,
      Amyda japonica. A high density of binding sites for 200 pM of 125I-labelled
      rANP(1-28) was located in the glomeruli of the kidney and the cortical portion of
      the adrenal gland. A moderate density of binding sites was seen in the arachnoid
      matter and choroid plexus of the third and lateral ventricles of the brain and
      the epididymis. A low density of binding sites was revealed in lamina propria of
      the mucosa of stomach and intestine, the seminiferous tubules of testes, and the
      epithelial layer of oviduct. In the presence of excess unlabelled rANP(1-28) (1
      microM), binding to these structures were completely displaced. Therefore,
      specific ANP receptors exist in the kidney, adrenal gland, stomach, intestine,
      oviduct, epididymis, seminiferous tubules and brain. The ANP system may be
      involved in physiological regulatory function in the freshwater turtle, Amyda
      japonica.

PMID- 8983172
TI  - Elevation of intracellular Ca2+ concentration in rabbit nonpigmented ciliary
      epithelial cells by allicin.
AB  - A previous study has shown that allicin produces changes in aqueous humor
      dynamics, and this study was conducted to examine possible cellular mechanisms.
      In rabbit nonpigmented ciliary epithelial cells, basal levels of [Ca2+]i were
      determined to be 164 +/- 34 nM. Allicin, a sulfhydryl-reactive agent, induced
      Ca2+ transients at 0.01 mM and at 0.2 mM, the Ca2+ transient peaked at 732 +/- 35
      nM. Allicin-induced Ca2+ transients were prevented by pretreatment with
      dithiothreitol which did not affect the basal Ca2+ levels. Allicin had only a
      slight, insignificant, effect on L-type Ca2+ currents, and allicin-induced Ca2+
      transients were also present under extracellular Ca(2+)-free conditions. These
      data suggest that intracellular Ca2+ stores are the most probable source of
      allicin's effect. Pretreatment of cells with ryanodine, an inhibitor of Ca(2+)
      induced-Ca(2+)-release, inhibited allicin-induced Ca2+ transients, but the basal
      Ca2+ levels were unaffected by ryanodine. Thus, allicin-induced Ca2+ transients
      are most likely mediated through ryanodine-sensitive intracellular Ca2+ stores.

PMID- 8983173
TI  - On the protection by ketorolac of reperfusion-induced heart damage.
AB  - This study shows that the nonsteroidal antiinflammatory drug, ketorolac, protects
      against myocardial damage induced by reperfusion. This effect was analyzed after
      5 min of coronary occlusion in rat hearts. The results indicate that ketorolac,
      at a dose of 1 mg/kg, effectively protects the heart against reperfusion
      arrhythmias. Furthermore, it protects from the release of lactate dehydrogenase
      and creatine kinase to the plasma. We propose that the protective effect of the
      drug might be due to its chelating action on calcium ions, thus preventing the
      overload of such cation in myocardial cells.

PMID- 8983174
TI  - Cellular and molecular features of lens differentiation: a review of recent
      advances.
AB  - In this paper, the more recent literature pertaining to differentiation in the
      developing vertebrate lens is reviewed in relation to previous work. The
      literature reviewed reveals that the developing lens has been, and will continue
      to be, a useful model system for the examination of many fundamental processes
      occurring during embryonic development. Areas of lens development reviewed here
      include: the induction and early embryology of the lens; lens cell culture
      techniques; the role of growth factors and cytokines; the involvement of gap
      junctions in lens cell-cell communication; the role of cell adhesion molecules,
      integrins, and the extracellular matrix; the role of the cytoskeleton; the
      processes of programmed cell death (apoptosis) and lens fibre cell denucleation;
      the involvement of Pax and Homeobox genes; and crystallin gene regulation.
      Finally, some speculation is provided as to possible directions for further
      research in lens development.

PMID- 8983175
TI  - Isolation of a marker for head-specific cell differentiation in hydra.
AB  - A cDNA was isolated from Hydra vulgaris coding for a 360 amino acid long
      polypeptide with no significant similarity to any known protein. In situ
      hybridization showed that the corresponding transcript is expressed exclusively
      in endodermal cells of the hypostome, hence its name hyp 1. Hyp 1 therefore
      represents a highly specific marker for the head region of hydra. In accordance
      with this, we found that hyp 1 expression was strong in tissues regenerating a
      head. Hyp 1 reappeared early during head regeneration, namely 6-8 h after
      initiation of regeneration by cutting. These findings imply that hyp 1 is an
      excellent marker for monitoring early events in head-specific differentiation
      processes in hydra.

PMID- 8983176
TI  - Spatial and temporal expression of 4f-rnp gene in Drosophila melanogaster.
AB  - We have recently discovered that a pre-messenger RNA (mRNA) encoded by the 4f-rnp
      gene in Drosophila melanogaster undergoes RNA editing by site-specific A-to-G
      conversions. In this report, we describe the spatial and temporal expression
      patterns of 4f-rnp mRNA transcripts during fly development. The 4f-rnp locus was
      mapped by polytene in situ hybridization experiments to the 4F1,2 bands at the
      distal tip of the X-chromosome, demonstrating that this gene is nuclear. We show
      that 4f-rnp is a single-copy gene by a combination of genomic Southern blot
      hybridization and restriction map analysis of clones isolated through chromosome
      walking techniques. Northern blot analysis indicates that two alternatively
      spliced messenger RNA transcripts, differing in length by 200-300 nucleotides,
      are synthesized in adult male and female flies, during embryogenesis and
      throughout the larval period. Using tissue in situ hybridization techniques that
      do not distinguish between the transcripts, we find that the distribution of 4f
      rnp mRNAs is specific to germline tissue in the ovary, demonstrating that these
      transcripts are maternally produced. During embryogenesis, 4f-rnp transcripts are
      localized within cells of most tissues, but they have a very distinct
      localization pattern within the segmental ganglia of the central nervous system.
      We discuss the significance that RNA editing is expected to have for the
      predicted 4F-RNP protein products that may be expressed throughout fly
      development and in high abundance within the fly's central nervous system.

PMID- 8983177
TI  - The lysosomal-associated membrane protein LAMP-1 is a novel differentiation
      marker for HC11 mouse mammary epithelial cells.
AB  - HC11 cells are a model for mammary epithelial cell differentiation. Following
      treatment with the lactogenic hormones glucocorticoids, insulin and prolactin the
      HC11 cells synthesize milk proteins. Stereological analysis at the
      ultrastructural level suggested that lysosomal biogenesis was activated following
      lactogenic hormone treatment of HC11 cells. Differentiation was also accompanied
      by an increase in the cellular content of tri- and tetra-antennary
      oligosaccharides, which were reactive with isolectin L4 from Phaseolus vulgaris
      (L-PHA). The lysosomal-associated membrane glycoproteins LAMP-1 and LAMP-2 are
      the major carriers of this glycosylation pattern. An analysis of LAMP-1 and LAMP
      2 expression levels showed that there was a dramatic increase in LAMP-1 following
      lactogenic hormone treatment of HC11 cells. The control of LAMP-1 expression is
      mainly post-transcriptional since the level of LAMP-1 RNA is not affected by
      lactogenic hormones. Stereological analysis also showed an increase in
      intermediate filament control of differentiated cells. Analysis of the
      cytokeratins expressed in differentiated cells suggests that HC11 cells have
      characteristics of a mammary-specific stem cell. Increase in lysosomal vesicles
      and their contents might play a role in intra- and extra-cellular remodeling,
      which is characteristic of cell differentiation.

PMID- 8983179
TI  - A transgenic mouse model that recapitulates the clinical features of both
      neonatal and adult forms of the skin disease epidermolytic hyperkeratosis.
AB  - Keratins are the major structural proteins of keratinocytes, which are the most
      abundant cell type in the mammalian epidermis. Mutations in epidermal keratin
      genes have been shown to cause severe blistering skin abnormalities. One such
      disease, epidermolytic hyperkeratosis (EHK), also known as bullous congenital
      ichthyosiform erythroderma, occurs as a result of mutations in highly conserved
      regions of keratins K1 and K10. Patients with EHK first exhibit erythroderma with
      severe blistering, which later is replaced by thick patches of scaly skin. To
      assess the effect of a mutated K1 gene on skin biology and to produce an animal
      model for EHK, we removed 60 residues from the 2B segment of HK1 and observed the
      effects of its expression in the epidermis of transgenic mice. Phenotypes of the
      resultant mice closely resembled those observed in the human disease, first with
      epidermal blisters, then later with hyperkeratotic lesions. In neonatal mice
      homozygous for the transgene, the skin was thicker, with an increased labeling
      index, and the spinous cells showed a collapse of the keratin filament network
      around the nuclei, suggesting that a critical concentration of the mutant HK1,
      over the endogenous MK1, was required to disrupt the structural integrity of the
      spinous cells. Additionally, footpad epithelium, which is devoid of hair
      follicles, showed blistering in the spinous layer, suggesting that hair follicles
      can stabilize or protect the epidermis from trauma. Blisters were not evident in
      adult mice, but instead they showed a thick, scaly hyperkeratotic skin with
      increased mitosis, resulting in an increased number of corneocytes and granular
      cells. Irregularly shaped keratohyalin granules were also observed. To date, this
      is the only transgenic model to show the typical morphology found in the adult
      form of EHK.

PMID- 8983178
TI  - The distribution and origin of keratin 20-containing taste buds in rat and human.
AB  - Sections of tissues containing lingual and extra-lingual taste buds were
      evaluated with monoclonal antibodies against cytokeratins. In the caudal third of
      the rat's tongue, keratin 20 immunoreactivity was restricted to taste buds,
      whereas keratins 7, 8, 18, and 19 were expressed in vallate and foliate taste
      buds and in cells of salivary ducts that merge with these taste epithelia. Hence,
      antibodies against keratin 20 most clearly distinguished differentiated taste
      cells from all other cells. In rat epiglottis, taste buds and isolated bipolar
      cells were keratin-20-positive. In rat nasopalatine papilla and palate,
      antibodies against keratin 20 identified Merkel cells, none of which was near to
      the keratin-20-negative taste buds. Nor were Merkel cells present at epiglottal
      taste buds or the keratin-20-negative fungiform taste buds or elsewhere in rat
      tongue. Hence, Merkel cells make no contribution to rat fungiform, epiglottal,
      nasopalatine, or palatal taste buds. Human and rat keratin-20-positive tissues
      are reported to be endodermal derivatives with the exception of Merkel cells and
      luminal urothelial cells. In rats the distribution of keratin-20-positive taste
      buds was in full agreement with the classical view that the posterior third of
      the tongue is derived from endoderm (keratin-20-positive taste buds), whereas the
      anterior two-thirds of the tongue is derived from stomadeal ectoderm (keratin-20
      negative taste buds). The equally intense keratin 20 immunoreactivity of human
      fungiform and vallate taste buds violates this traditional rostro-caudal
      segregation and suggests that endodermally derived tissues may be present in the
      tip of the human tongue.

PMID- 8983180
TI  - Distribution and complex organization of satellite DNA sequences in Aveneae
      species.
AB  - Distribution, organization, and molecular analysis of four unrelated satellite
      DNA components in Aveneae species are described. Highly repeated DNA elements
      were cloned from Helictotrichon convolutum (CON1 and CON2) and Helictotrichon
      compressum (COM1 and COM2). The lengths of the repeat monomers are 365 bp (CON1),
      562 bp (CON2), 346 bp (COM1), and 476 bp (COM2). Similar repeats were detected by
      dot blots, Southern blots, and by DNA sequencing in other species of the genus
      Helictotrichon, in Aveneae species, and in species of the tribes Andropogoneae
      and Oryzeae. All four satellite DNAs are differently distributed in the taxonomic
      groups mentioned above. Remarkably, the longer elements are built up in a complex
      pattern of either shorter subrepeats arranged in tandem (COM2) or by duplications
      inserted into an original 369-bp element (CON2). Shorter representatives, 190 bp,
      similar to CON1 elements occur in Holcus species. In Koeleria species, COM1
      related repeats are only 180 bp in length. No similarity was found among the
      sequences CON2, COM1, and COM2 or with sequences of other repetitive DNA elements
      of the grasses, but CON1 shows sequence similarity to an A genome specific
      repetitive DNA of Oryza (rice).

PMID- 8983181
TI  - Genetic and contig map of a 2200-kb region encompassing 5.5 cM on chromosome 1 of
      Arabidopsis thaliana.
AB  - In the course of the isolation of the MONOPTEROS (MP) gene, required for primary
      root formation in Arabidopsis thaliana, a yeast artificial chromosome (YAC)
      contig encompassing approximately 2200 kilobases corresponding to 5.5 cM on the
      top arm of chromosome 1 was established. Forty-six YAC clones were characterized
      and 12 new restriction fragment length polymorphism (RFLP) markers are presented.
      Three new codominant amplified polymorphic sequence (CAPS) markers were generated
      that enabled high resolution genetic mapping and correlation of physical and
      genetic distances along the contig. The map contributes to the completion of a
      physical map of the Arabidopsis genome and should facilitate positional cloning
      of other genes in the region as well as studies on genome organization. We also
      present another set of 11 physically linked probes, as well as mapping data for
      additional RFLP markers within a broader interval of 10.4 cM.

PMID- 8983182
TI  - Characterization of microsatellite markers in eastern white pine.
AB  - An enrichment cloning method was evaluated for the isolation of microsatellite
      loci from eastern white pine and the resulting markers were examined for
      polymorphisms. A 200-fold enrichment was achieved for highly abundant (AC)n
      repeats, but for much less abundant (ACAG)n repeats an enrichment of only 20-fold
      was obtained. Using a single set of PCR conditions, 19 microsatellite loci were
      identified from 77 primer pairs evaluated. Genotyping of 16 (AC)n loci in 16
      unrelated white pines from the north-central United States revealed an average of
      5.4 alleles per locus and an average observed heterozygosity of 0.515. Five loci
      were scored among megagametophytes from a single pine to obtain a haploid
      genotype of the segregating female meiotic products. All loci segregated
      according to Mendelian expectations and linkage was established for two of the
      loci. It was concluded that (AC)n loci are highly variable in this species and
      that SSR (simple sequence repeat) markers can be efficiently developed for genome
      mapping and population genetics studies.

PMID- 8983183
TI  - Addition-deletion mutations in transgenic Arabidopsis thaliana generated by the
      seed co-cultivation method.
AB  - We have characterized three mutant alleles of the CER2 gene of Arabidopsis
      thaliana by sequencing polymerase chain reaction products of this gene generated
      with template DNA isolated from lines MK1, BRL7, and BRL17. Sequence analysis of
      the amplification product from line BRL17 revealed a 17-bp deletion in the CER2
      gene. The CER2 gene of BRL7 differs from the wild-type sequence by a 2-base
      substitution and 2-base insertion. As both of these lines were isolated from the
      transformant populations generated by Dr. K. Feldmann and his collaborators, we
      suggest that these small rearrangements may be caused by unsuccessful T-DNA
      insertions. Comparative sequence analysis of the sequence of line MK1 and the
      wild type revealed a single nucleotide substitution located 360 bp downstream
      from the intron-exon junction that changes a tryptophan triplet TGG to TGA; i.e.,
      an opal non-sense mutation. In accordance with these observations, the cer
      phenotype of line MK1 was complemented by transformation with a fusion construct
      of the CaMV 35S promoter and the CER2 structural gene. Comparative analysis of
      the deduced amino acid sequences encoded by the CER2 gene from Arabidopsis and by
      the glossy2 gene from Zea mays revealed a significant similarity between them.
      This suggests that these gene products may have a similar biochemical function.

PMID- 8983184
TI  - Assignment of a gene(s) conferring apomixis in Tripsacum to a chromosome arm:
      cytological and molecular evidence.
AB  - Attempts are underway to locate and transfer genes conferring diplosporous
      apomixis from Tripsacum to maize. The objective of this study was to evaluate
      several apomictic and sexual maize-Tripsacum hybrids for the presence or absence
      of Tripsacum chromosomes, PCR-RAPD generated markers, and RFLP markers that would
      have an association with apomictic development. Cytological and molecular
      analysis resulted in the identification of the Tripsacum chromosome arm carrying
      the gene(s) conferring diplosporous apomixis. Evaluations made on apomictic
      sexually derived maize + Tripsacum addition lines and an apomictic line
      possessing a Mz6L-Tr16L translocation were used to establish the location of the
      gene(s). Results of the study indicate that the successful transfer of a single
      Tripsacum chromosome is all that is necessary to maintain apomictic reproduction
      in a maize background. Additional use of this material may facilitate the
      development of an apomictic maize prototype and the eventual isolation of the
      gene(s).

PMID- 8983185
TI  - Cloning and characterization of a highly repeated DNA sequence in Hordeum vulgare
      L.
AB  - A novel repetitive DNA sequence, R10hvcop, has been identified in the barley
      (Hordeum vulgare L.) genome. This 830 base pair (bp) DNA sequence has a 606-bp
      open reading frame and is present as approximately 1.96 x 10(5) copies per
      haploid barley genome. Southern blot analysis revealed that repetitive DNA
      elements containing R10hvcop and related sequences were dispersed within the
      barley chromosomes. Sequences similar to R10hvcop were also found in wheat
      (Triticum aestivum L.), rye (Secale cereale L.), and oat (Avena sativa L.) with
      copy numbers of 8 x 10(4), 1.39 x 10(5), and 7.9 x 10(4) per haploid genome,
      respectively. Sequences similar to R10hvcop were also present in the corn (Zea
      mays L. ssp. mays) genome, but they were not highly repeated. Barley, wheat, rye,
      oat, and corn showed species-specific restriction fragment length polymorphisms
      of R10hvcop and related sequences. Computer-based similarity searches revealed
      that R10hvcop is closely related to reverse transcriptase genes in
      retrotransposon-like elements of several plant species and of Drosophila. The
      highly repetitive nature, interspersed distribution, and high degree of
      similarity to reverse transcriptase genes suggests that R10hvcop contains the
      sequence of a diverged reverse transcriptase gene.

PMID- 8983186
TI  - Hygromycin-resistant calli generated by activation and excision of maize Ac/Ds
      transposable elements in diploid and hexaploid wheat cultured cell lines.
AB  - To investigate the activation and transposition of maize transposable elements in
      wheat cultured cells, plasmid DNAs containing the maize Ac/Ds elements located
      between the CaMV 35S promoter and a hygromycin B resistance gene (hph) were
      introduced into two wheat (Triticum aestivum and Triticum monococcum) cultured
      cell lines by microprojectile bombardment. In the first experiment, hph was
      activated by excision of the Ac element, which encodes transposase, in the two
      wheat cell lines. In the second experiment, the Ds element was excised by a
      stabilized Ac element, lacking inverted repeats of the Ac element and located on
      another plasmid, and therefore leading to activation of hph. After selection of
      bombarded cells by hygromycin B, many resistant calli were recovered in both
      wheat cell lines. The integration of hph and the Ac transposase gene was
      confirmed by PCR and genomic Southern analysis. The stable expression of hph and
      the transposase gene was also assessed by Northern blot and reverse transcriptase
      PCR analysis, respectively. Moreover, characteristic sequence alterations were
      found at Ac/Ds excision sites. These findings indicate that the maize Ac/Ds
      transposable elements are activated and excised by expression of the Ac
      transposase gene in both diploid and hexaploid wheat cells.

PMID- 8983187
TI  - Negative regulation of gene expression of a novel proline-, threonine-, and
      glycine-rich protein by water stress in Lycopersicon chilense.
AB  - We have isolated a full length cDNA clone (designated PTGRP) encoding a proline
      rich protein from leaves of Lycopersicon chilense. Sequence analysis of the 552
      bp insert revealed that the open reading frame encodes a 12.6-kDa protein. The
      deduced amino acid sequence of PTGRP consists of a C-terminal proline-rich domain
      with two identical repeat motifs Phe-Pro-Met-Pro-Thr-Thr-Pro-Ser-Thr-Gly-Gly-Gly
      Phe-Pro-Ser. The N terminus lacks proline and is hydrophobic. Unlike other
      proline-rich proteins this protein contains five glycine-rich repeat motifs (Gly
      X)n representative of glycine-rich proteins. Southern blot analysis showed that
      PTGRP is a member of a small gene family within the L. chilense genome. Northern
      blot experiments revealed that the PTGRP gene is significantly down regulated by
      water stress. PTGRP mRNA transcription decreased 5- to 10-fold in leaves and
      stems after 4-8 days of water stress. The mRNA reaccumulated when the drought
      stressed plants were rewatered. The in situ hybridization experiments also
      revealed that PTGRP mRNAs were more abundant in leaf sections of plants watered
      regularly compared with those of plants submitted to water stress. Down
      regulation of the PTGRP gene was also observed in desiccated cell suspensions of
      L. chilense and in those treated with abscisic acid, mannitol, and NaCl. Based on
      the common features of proline-rich proteins (high proline content, repeated
      motifs, and a putative signal peptide) and their involvement in the cell wall, it
      is likely that the PTGRP protein is targeted to the cell wall. Its down
      regulation by drought could be correlated with the remodeling of the plant cell
      wall in response to water stress.

PMID- 8983188
TI  - A codominant DNA marker closely linked to the rice nuclear restorer gene, RF-1,
      identified with inter-SSR fingerprinting.
AB  - A new molecular marker (OSRRf) closely linked to the nuclear restorer gene (Rf-1)
      for fertility in rice has been found. The Rf-1 gene is essential for hybrid rice
      seed production. A PCR-fingerprinting technique using simple sequence repeats
      (SSRs) was applied to compare two near-isogenic lines with (MTC-10R) or without
      (MTC-10A) the Rf-1 gene. Of 76 inter-SSR primers tested, only one primer,
      (AG)8YC, generated polymorphisms. The tetranucleotide repeats generating
      polymorphisms were found within each amplicon. the genetic distance between OSRRf
      and Rf-1 was 3.7 +/- 1.1 cM. As in the case of a codominant marker, this marker
      will be applied not only to breeding both restorer lines and maintainer lines,
      but also to the purity management of hybrid rice seeds.

PMID- 8983189
TI  - Differential sensitivity of some human alphoid and classical satellite DNA
      regions from lymphocyte chromosomes to in situ exonuclease III digestion.
AB  - Fluorescent in situ hybridization of alphoid and classical satellite III DNA
      sequences was performed on fixed chromosomes from human lymphocytes that were
      previously digested in situ with exonuclease III to produce single-stranded DNA
      motifs. Digital image analysis showed that while labeled alphoid satellite DNAs
      produced signals of similar strength to thermally denatured chromosomes, those of
      classical satellite III DNAs of chromosomes 9 and Yq were around 50% weaker. This
      result shows a differential sensitivity of these satellite DNA regions to in situ
      exonuclease III digestion and suggests structural differences in the higher-order
      organization of both subchromosomal constitutive heterochromatic regions.

PMID- 8983190
TI  - Chromosomal location of three wheat sequences with homology to pollen allergen
      encoding, DNA replication regulating, and DNA (cytosine-5)-methyltransferase
      genes in wheat and rye.
AB  - Three wheat sequences, shown to be homologous to pollen allergen encoding, DNA
      replication regulating, and DNA (cytosine-5)-methyltransferase genes were
      localized on chromosomes using nullisomic-tetrasomic wheat ('Chinese Spring') and
      wheat-rye ('Chinese Spring'/'Imperial') addition lines. Whereas the loci for the
      pollen allergen encoding sequence (Tri a III) were shown to be located on
      homoeologous group 4, the DNA replication regulating (Rep) and DNA (cytosine-5)
      methyltransferase (Mtase) genes were located to homoeologous groups 1 and 7,
      respectively, of Triticeae. Chromosomal rearrangements in wheat and rye relative
      to each other are discussed.

PMID- 8983191
TI  - Development of a SCAR marker linked to the I gene in common bean.
AB  - Two 24-mer SCAR primers (SW13) were developed from a previously identified 10-mer
      RAPD primer (OW13(690)) linked to the I gene, which conditions resistance to bean
      common mosaic virus (BCMV) in common bean. Linkage between SW13 and the I gene
      was tested in three F2 populations segregating for both SW13 and the I gene:
      N84004/Michelite (1.0 +/- 0.7 cM), Seafarer/UI-114 (1.3 +/- 0.8 cM), and
      G91201/Alpine (5.0 +/- 2.2 cM). SW13 proved to be more specific and reproducible
      than the OW13(690) RAPD marker. Using different heat-stable DNA polymerases, SW13
      amplified a single 690-bp fragment linked to the I gene that more consistently
      permitted the identification of resistant plants. In addition, the presence of
      the I gene was detected using SW13 in genotypes originating from different gene
      pools of Phaseolus vulgaris L., indicating a broad utility of this marker for
      bean breeding programs.

PMID- 8983192
TI  - Localization of rDNA genes in European eel (Anguilla anguilla) by FISH.
AB  - A probe containing most of the transcription unit of the major ribosomal genes of
      Xenopus laevis has been used to localize the rDNA cluster of European eel
      (Anguilla anguilla) by fluorescence in situ hybridization (FISH). Only on NOR
      bearing chromosome pair has been found. The results obtained with this technique
      confirm the size polymorphism of the NOR revealed previously by other classical
      cytogenetic techniques.

PMID- 8983193
TI  - Changes in the ultrastructural localization of mRNA for a circadian regulated
      protein.
AB  - The amount of the luciferin (substrate) binding protein (LBP) in extracts of the
      bioluminescent marine dinoflagellate Gonyaulax polyedra increases by about 10
      fold during a 6-hour period spanning the end of the day- and the early night
      phases, and then decreases by the same amount approximately 12 hours later.
      Previous studies have indicated that synthesis of the protein is regulated
      translationally. The experiments described here were undertaken to gain insight
      into the mechanism of this control. Evidence was obtained for the existence of
      mRNA-binding proteins that could have a regulatory function. In addition,
      circadian-related differences were observed in the total amount of mRNA as well
      as in the subcellular distribution of lbp mRNA.

PMID- 8983195
TI  - Semiautomated multilocus genotyping of Pacific salmon (Oncorhnychus spp.) using
      microsatellites.
AB  - We report the development of a semiautomated multilocus genotyping system for
      Pacific salmon using four-color fluorescent detection of microsatellites. An
      initial screening of microsatellites was conducted on five species of Pacific
      salmon (Oncorhynchus spp.) and Atlantic salmon (Salmo salar) using 35 primer
      pairs developed from six species of salmonid. The number of loci that amplified
      varied by species from 11 (chum salmon) to 22 (chinook salmon). We then tested co
      amplification of microsatellites in chinook, coho, and sockeye salmon and
      developed six-locus multiplex systems. The species-specific multiplex systems
      were applied to two populations using a sequencer/gene scanner (Perkin-Elmer
      Applied Biosystems, Inc. [ABI] 373A). The genetic variability at each locus was
      calculated to evaluate the utility of this system for genetic studies.
      Significant differences in allele frequencies were observed between populations
      in 14 of 18 pair-wise comparisons. Average heterozygosity ranged from 0.47 in
      Togiak River coho salmon to 0.75 in Dungeness River chinook salmon. Observed
      heterozygosities ranged from 0 at One mu 1 in Togiak River coho to 0.96 at Ssa85
      in Dungeness River chinook. The probability of match (PM) for each six-locus
      multiplex system was 4.0 x 10(-10), 7.2 x 10(-8), and 3.2 x 10(-7) for chinook,
      coho, and sockeye, respectively. The average polymorphic information content
      (PIC) was 0.77, 0.56, and 0.60 for chinook, coho, and sockeye, respectively. The
      microsatellite loci used here show promise for high-resolution genetic studies of
      Pacific salmon such as fine-scale population analysis kinship, and parentage
      studies.

PMID- 8983194
TI  - Homeobox genes in the Ctenophora: identification of paired-type and Hox
      homologues in the atentaculate ctenophore, Beroe ovata.
AB  - Homeobox-containing genes are a phylogenetically widespread family of
      transcription factors that can regulate cell fates during embryogenesis. Two
      distinct homeobox gene sequences are described for the atentaculate ctenophore
      Beroe, the first homeoboxes to be identified in this phylum. Beroe homeobox
      fragments were cloned in a survey of genomic DNA using polymerase chain reaction
      (PCR). Parsimony, neighbor-joining, and maximum likelihood methods were used to
      infer the orthology of the ctenophore sequences to specific homeoboxes from
      higher metazoans including Drosophila, Caenorhabditis elegans, and humans. Cteno
      paired appears most closely related to paired-typed homeoboxes. This is the first
      evidence of a paired-type homeobox in one of the so-called diploblastic animals.
      Cteno-Hoxl appears most closely related to members of the Hox class, particularly
      Antennapedia.

PMID- 8983196
TI  - Cloning and sequencing of cDNAs encoding ribonucleotide reductase from zebrafish
      Danio rerio.
AB  - We have cloned and sequenced cDNAs coding for the R1 and R2 proteins of
      ribonucleotide reductase from zebrafish (Danio rerio). This ribonucleotide
      reductase shows high amino acid sequence identity to those of other vertebrates.
      The R1 cDNA has a coding sequence of 2382 bp, yielding a 794 amino acid protein,
      and the R2 cDNA has a coding sequence of 1158 bp, yielding a 386 amino acid
      protein. The zebrafish R1 shows 94% similarity and R2 shows 91% similarity to the
      human R1 and R2, respectively. The similarity extends to intron positions, of
      which the equivalent of mouse R2 intron 3 has been studied.

PMID- 8983197
TI  - Zebrafish translation elongation factor EF1 alpha mRNA: sequence and secondary
      structures.
AB  - We have determined the complete sequence of the translation elongation factor EF1
      subunit alpha (EF1 alpha) mRNA of zebrafish, and the 3'-untranslated sequence of
      EF1 alpha mRNA of halibut. The 5'-untranslated leader sequence of the EF1 alpha
      mRNA starts with a polypyrimidine tract. This feature is shared with the mRNAs
      for ribosomal proteins, where it affects the utilization of mRNA by ribosomes.
      However, the secondary structures of these leader sequences may differ. 5'
      Polypyrimidine tracts of vertebrate EF1 alpha mRNAs participate in the formation
      of stable stem-loop structures, whereas those of 15 randomly chosen mRNAs for
      ribosomal proteins do not. This difference may provide a basis for differential
      control of translation for the two classes of mRNA. The 3'-untranslated sequences
      of vertebrate EF1 alpha mRNA have diverged little during evolution. Analyses of
      sequence and putative secondary structures suggest that both sequence-specific
      interactions and secondary structures may have contributed to sequence
      conservation.

PMID- 8983198
TI  - Isolation of cDNA encoding a putative chitinase precursor in the kuruma prawn
      Penaeus japonicus.
AB  - Amino acid sequences of chitinases have been determined in insects, plants,
      yeast, and bacteria, but not in crustaceans. We searched for chitinase-encoding
      cDNA in the kuruma prawn Penaeus japonicus by polymerase chain reaction (PCR)
      amplification of hepatopancreas cDNA using degenerate oligonucleotide primers
      derived from the two conserved regions of known chitinases. Using a PCR product
      as a probe, a cDNA clone was isolated. This clone contains an open reading frame
      for a protein (named Pjchi-1) of 572 amino acids that exhibits sequence
      similarities to known chitinases, especially to a chitinase from the tobacco
      hornworm Manduca sexta. Transcription of the mRNA was detected in the
      hepatopancreas but not in epidermal tissues.

PMID- 8983200
TI  - Molecular cloning and sequence analysis of two cDNAs coding for putative anionic
      trypsinogens from the colonial Urochordate Botryllus schlosseri (Ascidiacea).
AB  - Botryllus schlosseri is a colonial marine invertebrate that belongs to the
      subphylum Urochordata. Previously we analyzed the activity of a serine protease
      in this species, and cloned a tunicate chymotrypsin-like molecule. In the present
      study we further analyzed the protease activity of this animal, and found
      biochemical evidence also for specific trypsin-like activity. Subsequently we
      utilized a degenerate polymerase chain reaction (PCR) primer to clone two B.
      schlosseri cDNAs coding for two different putative trypsinogens, each 243 amino
      acids long, that differ within the coding region in 42 amino acids and 99
      nucleotides. Both clones feature the characteristics of animal anionic
      trypsinogens. Sequence analysis of the tunicate putative trypsinogens revealed
      the invertebrate characteristics of three disulfide bridges, and higher
      similarity to invertebrate than to vertebrate trypsinogens. We therefore propose
      that the typical characteristics of vertebrate trypsinogens evolved after the
      divergence of Urochordates and Cephalochordates.

PMID- 8983199
TI  - DNA sequencing of formalin-fixed crustaceans from archival research collections.
AB  - Marine invertebrate collections have historically been maintained in ethanol
      following fixation in formalin. These collections may represent rare or extinct
      species or populations, provide detailed time-series samples, or come from
      presently inaccessible or difficult-to-sample localities. We tested the viability
      of obtaining DNA sequence data from formalin-fixed, ethanol-preserved (FFEP) deep
      sea crustaceans, and found that nucleotide sequences for mitochondrial 16S rRNA
      and COI genes can be recovered from FFEP collections of varying age, and that
      these sequences are unmodified compared with those derived from frozen specimens.
      These results were repeatable among multiple specimens and collections for
      several species. Our results indicate that in the absence of fresh or frozen
      tissues, archived FFEP specimens may prove a useful source of material for
      analysis of gene sequence data by polymerase chain reaction (PCR) and direct
      sequencing.

PMID- 8983201
TI  - Sequence variation of the first internal spacer (ITS-1) of ribosomal DNA in
      ahermatypic corals from California.
AB  - Interspecific and intraspecific variation in the first internal transcribed
      spacer region (ITS-1) of ribosomal DNA (rDNA) was examined in two species of
      ahermatypic corals (lacking symbiotic algae and non-reef-building) with different
      dispersal characteristics, Paracyathus stearnsii (gamete-spawner with pelagic
      larvae) and Balanophyllia elegans (brooder with benthic larvae) from California.
      An approximately 300-bp region of the ITS-1 was amplified by polymerase chain
      reaction (PCR) and sequenced from populations at Pt. Loma, La Jolla, Monterey
      Bay, and Santa Catalina Island and compared for each species and compared with
      the same region from the hermatypic coral Favia lizardensis. There was a wide
      range of sequence variation in the ITS-1 region between the species, and these
      differences readily distinguished the taxa. Intraspecific comparisons of P.
      stearnsii individuals showed very little sequence variation (two polymorphisms)
      in the ITS-1 region. In contrast to P. stearnsii, we found 14 variable nucleotide
      sties in the ITS-1 region for B. elegans. Although there were no nucleotide sites
      that diagnostically separated central and southern populations, these findings
      indicate that the ITS-1 region is variable in B. elegans and a promising source
      for nuclear molecular markers in ahermatypic corals.

PMID- 8983202
TI  - The combinatorial library: a multifunctional resource.
AB  - About 10 years ago Dr. Mario Geysen introduced a method for synthesizing a large
      number of peptides on solid supports simultaneously. This work has subsequently
      been generalized by many other research groups to develop technologies that allow
      from hundreds to thousands to millions of compounds to be synthesized in
      parallel. These large collections of compounds have been now termed combinatorial
      libraries. Much of the effort in this field has been directed to drug discovery.
      However, in recent years, these libraries have been shown to be very useful for
      finding compounds (such as inhibitors, binding agents, enzymes, and antibodies)
      that satisfy specific requirements. Thus these techniques represent a very
      excellent resource for the discovery of compounds for a variety of
      biotechnological process needs.

PMID- 8983203
TI  - Cybernetic model for the growth of Saccharomyces cerevisiae on melibiose.
AB  - Cybernetic modeling has traditionally been used in the modeling of microbial
      growth on multiple substrates. In this paper, cybernetic modeling has been
      applied to serve as a model for growth on substrates such as melibiose, which are
      disaccharides and enzymatically degrade to a monosaccharide mixture in the
      fermentation broth. The enzyme alpha-galactosidase has been shown to be strongly
      induced in the presence of galactose and severely repressed by glucose. In the
      present model, the relative concentration of alpha-galactosidase has been linked
      to that of the key enzyme for galactose metabolism. The enzymatic degradation
      process is placed under the control of the cybernetic variables. The maximum rate
      of melibiose degradation vm and the Monod parameters for growth of Saccharomyces
      cerevisiae on pure glucose and galactose were estimated by batch growth
      experiments. S. cerevisiae growth on melibiose and a mixture of melibiose and
      glucose under a variety of preculturing conditions was simulated. Depending on
      the rate of enzymatic degradation (i.e., the value of vm), the cell mass profile
      for microbial growth on a disaccharide can resemble profiles for growth on a
      single substrate (melibiose) or can resemble diauxie growth. Experiments indicate
      that the model is able to accurately predict the cell mass profiles for yeast
      growth.

PMID- 8983204
TI  - Expression of Vitreoscilla hemoglobin is superior to horse heart myoglobin or
      yeast flavohemoglobin expression for enhancing Escherichia coli growth in a
      microaerobic bioreactor.
AB  - Expression of a gene encoding hemoglobin (VHb) from the aerobic bacterium
      Vitreoscilla sp. in several organisms, including Escherichia coli, has been shown
      to improve microaerobic cell growth and enhance oxygen-dependent product
      formation. The suitability of VHb to enhance microaerobic metabolism has been
      suggested to depend on its unusual oxygen binding characteristics. To examine
      whether hemoproteins of other origins can also elicit the positive effects VHb
      exerts in microaerobic E. coli cells, we subcloned the genes encoding
      Vitreoscilla VHb, horse heart myoglobin (HMb), and yeast flavohemoglobin (YFb)
      behind the IPTG-inducible tac promoter on a medium-copy-number vector and
      transformed these globin-expression plasmids into E. coli MG1655 and DH5 alpha.
      Biologically active VHb, HMb, and YFb were produced from these constructions in
      E. coli as judged by their ability to abduct carbon monoxide. The presence of HMb
      increased the growth of wild-type cells during the early stages of fed-batch
      growth, but the final optical densities of HMb-expressing cultures were
      comparable with the wild-type control not synthesizing HMb. The presence of VHb
      increased the cell density by 70% under the same cultivation conditions. The
      expression of wild-type YFb reduced the final cell density by 30% relative to the
      non-globin-expressing control.

PMID- 8983205
TI  - Biodegradation of hydrogen sulfide by a laboratory-scale immobilized Pseudomonas
      putida CH11 biofilter.
AB  - A heterotrophic Pseudomonas putida CH11 was isolated from livestock farming
      wastewater and applied for the treatment of H2S-containing gas. Extensive tests
      including removal characteristics, metabolic products, and removal efficiencies
      of H2S by P. putida CH11 were examined in batch and continuous systems. The
      optimum pH required to remove hydrogen sulfide was found in the range of 6-8. The
      maximum removal rate and the saturation constant were calculated to be Vm = 1.36
      g S/day.kg dry bead and Ks = 45.9 ppm, respectively. The main metabolic product
      of H2S oxidation was determined to be elemental sulfur. When P. putida CH11 was
      immobilized within Ca alginate, the cells exhibited high H2S removal efficiency,
      in excess of 96%, at concentration of hydrogen sulfide from 10 to 150 ppm (flow
      rates of 36 and 72 L/h). These results suggest that P. putida CH11 immobilized
      within Ca alginate has the potential to be used as a H2S removal agent.

PMID- 8983206
TI  - Extraction behavior of hemoglobin using reversed micelles by dioleyl phosphoric
      acid.
AB  - A new surfactant, dioleyl phosphoric acid (DOLPA), has been applied to the
      extraction of hemoglobin using reversed micelles. The reversed micelles formed by
      DOLPA can easily extract hemoglobin from aqueous to reversed micellar solutions.
      DOLPA is the first surfactant to extract hemoglobin completely without using any
      cosurfactants. On the basis of the difference between DOLPA and AOT reversed
      micelles in the forward extraction behavior of hemoglobin, the nature of the
      interfacial complex that would be formed between surfactants and hemoglobin at
      the oil--water interface was found to be the dominant factor in determining the
      extraction efficiency of hemoglobin be reversed micelles. In addition, back
      transfer studies of hemoglobin from the DOLPA reversed micelles were also carried
      out by the phase transfer method. It was found that hemoglobin, once dissolved
      into the DOLPA reversed micelles, is not transferred to a fresh aqueous solution
      even when the conditions are adjusted to not allow the forward transfer of
      hemoglobin. However, the addition of several kinds of alcohol drastically
      improved the yield in the back-transfer of hemoglobin. The efficiency in the back
      transfer of hemoglobin strongly depends on the aqueous conditions that are in
      contact with the reversed micelles, such as pH, ionic strength, and alcohol
      concentration. A pH higher than the pI of hemoglobin, a salt concentration lower
      than that of the water pool, and the proper concentration of alcohol are required
      for the recovery aqueous phase to ensure the back-transfer of hemoglobin from the
      DOLPA reversed micelles.

PMID- 8983207
TI  - Molten globule intermediate of recombinant human growth hormone: stabilization
      with surfactants.
AB  - We demonstrate that a surfactant-stabilized molten globule intermediate exists
      for recombinant human growth hormone (rhGH), is very hydrophobic, and tends to
      form aggregates. Characterization of this intermediate included equilibrium
      denaturation measured by electron paramagnetic resonance (EPR) and CD
      spectroscopy, assessment of aggregation during refolding, and fluorescence
      studies of its binding to the hydrophobic probe, 1-anilinonapthalene-8-sulfonate
      (1,8-ANS). We have found that at 4.5 M guanidinium hydrochloride (GuHCl), a
      molten globule intermediate of rhGH is stabilized and results in significant
      aggregation upon refolding. This intermediate is populated by the addition of the
      nonionic surfactant, Tween. This surfactant also reduces the extent of
      aggregation during refolding of rhGH from 4.5 M GuHCl. Overall, our studies
      reveal that rhGH forms a molten globule-like intermediate during folding and this
      intermediate self-associates. This self-association is reduced upon formation of
      a Tween-rhGH complex. Tween also binds to the native protein. Thus, nonionic
      surfactants such as Tween may act like molecular chaperones in facilitating
      protein folding while not altering the native conformation.

PMID- 8983208
TI  - Cyclic operation of ceramic-matrix animal cell bioreactors for controlled
      secretion of an endocrine hormone. A comparison of single-pass and recycle modes
      of operation.
AB  - Controlled secretion processes for the production of secretory proteins in
      monolayer culture have been described previously (Grampp et al. Adv. Biochem.
      Eng./ Biotechnol. 1992, 46, 35-62), but little is known about the feasibility of
      scaling such processes into high-density bioreactors. Two immobilized-cell,
      ceramic-matrix bioreactor configurations were tested using the beta TC-3 cell
      model system which, in monolayer culture, can be manipulated to secrete murine
      insulin in a highly controlled manner. One reactor was configured with an
      external recirculation reservoir for oxygen transfer and was operated as a
      conventional immobilized bed/recycle reactor. The other reactor was configured as
      a single-pass perfusion system with oxygen supplied by diffusion from silicone
      tubing positioned proximal to the porous walls of the ceramic matrix. After
      inoculation with beta TC-3 cells, both systems were perfused with serum
      supplemented medium to stimulate cell growth, and they ultimately attained high
      densities (approximately 5 x 10(8) cells/mL of pore volume). To initiate
      controlled secretion operations, the reactor cores were washed with a serum-free
      basal medium, then exposed to a serum-free discharging medium containing
      secretory stimulants. Following several hours of discharging, the reactors were
      washed again, then switched to a serum-containing medium designed to quench the
      regulated secretion process. For the single-pass reactor these cycling operations
      were simple to implement and were effective in promoting the cyclic discharge and
      recharge of murine insulin. Because of the ability to reduce the perfusion rate
      in the single-pass reactor independent of oxygen transfer, the discharged insulin
      was captured in a relatively small volume (2 reactor core hold-up volumes),
      yielding a mean product concentration 10-fold greater than in the steady-state
      perfusate. Cyclic operation of the recirculating reactor was more difficult due
      to the complexity of switching between recirculation reservoirs, and the
      introduction of air bubbles during such operations resulted in the loss of
      biomass from the reactor after one cycle. Even in the first discharging cycle,
      the insulin yield was much lower than in the perfusate from the single-pass
      reactor, despite the comparable metabolic rates. The single-pass reactor was
      cycled successfully through four discharging and recharging episodes and
      maintained its ability to discharge insulin, albeit at a slower rate after the
      first discharge. Overall, 50-60% of the insulin secreted during the 48 h cycles
      was recovered during the brief discharging episodes. When insulin secretion rates
      and discharging yields were normalized to metabolic activity, neither high
      density reactor system performed as well as did identically treated control T
      flask cultures. It is hypothesized that the productivity and responsiveness of
      the high-density, pore-immobilized beta TC-3 cells are lower than in monolayer
      culture.

PMID- 8983209
TI  - Possible role of arachidonic acid in stress-induced cytochrome P450IA1 activity.
AB  - We have previously reported that a microcarrier-attached human hepatoma (Hep G2)
      cell line responds to hydrodynamic shear upon transfer to an agitated, clean,
      autoclaved spinner flask with a transient increase in cytochrome P450IA1 (CYPIA1)
      activity. Physiological changes induced by hydrodynamic stress could be
      problematic in the scaleup of microcarrier cultures. A better understanding of
      how stress alters cell physiology may assist in reactor scaleup. The induction of
      CYPIA1 activity was dependent on the agitation level of the cultures, and the
      level of CYPIA1 induction was comparable to that obtained with exposure to
      approximately 0.1 nM TCDD (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin). It has been
      well documented that hydrodynamic shear stress can cause alterations in the
      metabolism of phospholipid membrane-bound arachidonic acid (AA) in adherent cells
      in a parallel plate system. The present study was carried out to determine if
      either AA or a metabolite of AA was involved in the induction of CYPIA1 activity
      in the microcarrier cultures of Hep G2 cells. Addition of exogenous AA followed
      by initiation of the stress resulted in an increase in the level of CYPIA1
      activity. Pretreatment of the cultures with quinacrine, an inhibitor of
      phospholipase A2, reduced the stress-induced CYPIA1 activity. Furthermore,
      addition of propranolol, an inhibitor of phosphatidic acid phosphohydrolase,
      resulted in an increase in the response in addition to sustaining the induced
      enzyme activity. Pretreatment with the cyclooxygenase inhibitor, indomethacin, or
      the lipoxygenase inhibitor, caffeic acid, had no effect on the response,
      suggesting that the cyclooxygenase and lipoxygenase pathways were not involved in
      generating AA metabolites that alter CYPIA1 activity. The agent,
      nordihydroguaiaretic acid, blocks the monooxygenase pathway and blocks CYPIA1
      activity increases. These observations suggest a possible mechanism where the
      stress on the cells induces phospholipase D, resulting in the formation of
      phosphatidic acid which then activates phospholipase A2, resulting in the release
      of AA. Further, these results are consistent with a mechanism in which the
      metabolism of AA, most likely through the monooxygenase pathway, results in a
      metabolite that by a yet unknown mechanism induced CYPIA1.

PMID- 8983210
TI  - Use of the Centritech Lab centrifuge for perfusion culture of hybridoma cells in
      protein-free medium.
AB  - As part of an effort to develop a suspension-culture perfusion-based process with
      high flow rate without the fouling and antibody retention inherent to filter
      based cell-separation devices, we have evaluated and contributed to the
      development of the Centritech Lab centrifuge for the perfusion culture of
      hybridoma cells in protein-free medium. Culture start-ups showed that cell growth
      and monoclonal-antibody (MAb) production rates were similar in both a spinner
      flask and continuous centrifugation coupled to a bioreactor. The centrifuge
      efficiently separated viable cells from dead ones. Viable-cell recoveries were
      never below 98%, whereas dead-cell recoveries were usually around 80%. The cell
      content of the centrifuge supernatant and concentrate was strongly determined by
      the total amount of cells, viable and dead, in the culture broth, but an
      influence of the centrifugation parameters (feed rate, times of separation and
      discharge, and rotor speed) was observed. This understanding of the separation
      process inside the centrifuge is important and may apply to other similar
      devices. Monoclonal antibodies were not retained in the bioreactor during
      centrifugation perfusion. However, whereas similar growth rates were obtained in
      perfusion cultures using either continuous centrifugation or filtration, MAb
      concentrations were 35% lower in the former case. Utilization of the centrifuge
      in an intermittent fashion decreased the daily cell residence time outside the
      bioreactor, the daily pelleted-cell residence time in the centrifuge, and the
      frequency of cell passage to the centrifuge. This led to higher viable-cell
      numbers in the bioreactor and an accompanying increase in MAb concentrations, 225
      250 mg of IgM L-1, equal to the performance of filter-based perfusion systems
      with the same cell line. It was hypothesized that having cells periodically
      packed at the bottom of the centrifuge insert (up to 800 x 10(6) cells mL-1) is
      deleterious to the culture by exposing the pelleted cells to prolonged nutrient
      limitations.

PMID- 8983211
TI  - Engineering dental pulp-like tissue in vitro.
AB  - Injury or infection of adult dental pulp often necessitates root canal therapy.
      This terminates dentin formation and subsequent tooth maturation. In addition,
      the synthetic materials currently utilized to replace lost tooth structure are
      not capable of completely replacing the function of the lost tissue, and often
      fail over time. This report describes a technique to engineer new pulp-like
      tissues utilizing cultured cells and synthetic extracellular matrices.
      Fibroblasts were obtained from human adult dental pulps and multiplied in
      culture. These cells were subsequently seeded onto synthetic matrices fabricated
      from fibers (approximately 15 microns in diameter) of polyglycolic acid (PGA).
      The pulp-derived fibroblasts adhered to the fibers, proliferated, and formed a
      new tissue over 60 days in culture with a cellularity similar to that of native
      pulp. These tissues may find application in the regeneration of oral tissues and
      may provide novel systems in which to study the biocompatibility of materials and
      chemicals used in dentistry.

PMID- 8983212
TI  - beta-Lactamase recovery from E. coli cell lysate via two-phase electrophoresis.
AB  - beta-Lactamase was recovered from Escherichia coli cell lysate by a novel cell
      debris removal method using two-phase electrophoresis. The cells were harvested
      by centrifugation after fermentation, resuspended in a low ionic strength
      electrophoresis buffer, lysed, and combined with a poly(ethylene glycol)/dextran
      aqueous two-phase system in the same buffer. The cell lysate was subjected to a
      40 V/cm electric field oriented perpendicular to the phase interface for 90 min.
      Experiments were conducted both with and without a nucleic acid precipitation
      step using poly(ethylene imine) (PEI). For PEI-treated lysate at pH 5, the
      positively charged beta-lactamase was directed to the upper phase, while
      negatively charged contaminants (including cell debris, nucleic acid/PEI
      precipitates, and negatively charged proteins) were directed to the lower phase
      with the applied field. beta-Lactamase yield in the upper phase was 81%, while
      cell debris and nucleic acids partitioned almost exclusively to the lower phase.
      For untreated lysate, beta-lactamase did not move in the electric field due to
      strong interaction with nucleic acids in solution.

PMID- 8983213
TI  - A lectin from mycelia of the fungus Ganoderma lucidum.
AB  - A lectin (GLL-M) was isolated from mycelia of Ganoderma lucidum using affinity
      chromatography on BSM-Toyopearl. GLL-M is a monomer in its native form with a
      M(r) of 18,000. Another lectin was also purified from fruiting bodies of the same
      fungus. The two lectins were partially compared with each other.

PMID- 8983214
TI  - Pregnane glycosides from Sansevieria trifasciata.
AB  - Phytochemical analysis of the whole plant of Sansevieria trifasciata, one of the
      most common Agavaceae plants, has resulted in the isolation of four new pregnane
      glycosides. Their structures have been determined by spectroscopic analysis and
      acid- and alkaline-catalysed hydrolysis to be 1 beta,3 beta-dihydroxypregna-5,16
      dien-20-one glycosides. This is believed to be the first report of the isolation
      of the pregnane glycosides from a plant of the family Agavaceae.

PMID- 8983215
TI  - Megastigmane glycosides from Salvia nemorosa.
AB  - From the aerial parts of Salvia nemorosa, three new megastigmane glycosides,
      salvionosides A-C, were isolated, along with the known compounds, (6S,9R)- and
      (6S,9R)-roseosides, (6R,9R)- and (6R,9S)-3-oxo-alpha-ionol glucosides and blumeol
      C glucoside. The structures of the new compounds were elucidated on the basis of
      spectral and chemical evidence.

PMID- 8983216
TI  - Isolation and structure elucidation of three triterpenoid saponins from Acacia
      auriculiformis.
AB  - Three new triterpenoid saponins, proacaciaside-I, proacaciaside-II and acaciamine
      isolated from the fruits of Acacia auriculiformis, were identified as acacic acid
      lactone-3-O-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranoside, acacic acid
      lactone-3-O-alpha-L-arabinopyranosyl (1 --> 2)-beta-D-glucopyranoside and acacic
      acid lactone-3-O-alpha-L-arabinopyranosyl (1 --> 6)-2-acetamide-2-deoxy-beta-D
      glucopyranoside based on their spectral properties and some chemical
      transformations.

PMID- 8983217
TI  - Pregnane glycosides from Hemidesmus indicus.
AB  - Three new pregnane oligoglycosides, medidesmine, hemisine and desmisine isolated
      from the plant Hemidesmus indicus were identified as sarcostin-3-O-alpha-D
      glucopyranosyl (1 --> 4)-O-beta-D-digitoxopyranosyl (1 --> 4)-O-beta-D
      oleandropyranoside, calogenin-3-O-beta-D-cymaropyranosyl (1 --> 4)-O[3-O
      methyl]beta-D-glucopyranosyl (1 --> 4)-O-beta-D-glucopyranosyl (1 --> 4)-O-beta-D
      cymaropyranoside and calogenin-3-O-beta-D-xylopyranosyl (1 --> 4)-O-beta-D
      digitoxopyranosyl (1 --> 4)-O-beta-D-xylopyranosyl (1 --> 4)-O-beta-D
      digitoxopyranoside, respectively, with the help of FAB-MS, EI-MS, 1H and 13C NMR
      spectroscopy, along with chemical transformations.

PMID- 8983219
TI  - [8th spring meeting of the Japanese Society of Allergology. Yokohama, Japan.
      April 25-27, 1996. Abstracts].

PMID- 8983218
TI  - Two acylated anthocyanins from purple sweet potato.
AB  - Two new acylated anthocyanins were isolated from the storage root of Ipomoea
      batatas. On the basis of spectroscopic analyses, these compounds were identified
      as the 3-O-(6-O-trans-caffeyl-2-O-beta-glucopyranosyl-beta-glucopyranoside)-5-O -
      beta-glucoside of cyanidin and peonidin.

PMID- 8983220
TI  - [46th general meeting of the Japanese Society of Allergology, Tochigi, Japan.
      October 30-November 1, 1996. Abstracts].

PMID- 8983221
TI  - [The 24th annual meeting of the Japanese Society of Clinical Immunology. Tokyo,
      Japan. September 25-27, 1996. Abstracts].

PMID- 8983222
TI  - [The 100th annual meeting of the Japanese Ophthalmological Society. Kyoto, Japan.
      May 15-19, 1996. Abstracts].

PMID- 8983223
TI  - [The 84th annual meeting of the Japanese Urological Association. Okayama, Japan.
      April 3-6, 1996. Abstracts].

PMID- 8983224
TI  - [The 55th annual meeting of the Japan Radiological Society. Yokohama, Japan.
      April 2-4, 1996. Abstracts].

PMID- 8983225
TI  - [The 32nd autumn meeting of the Japan Radiological Society. Sapporo City,
      Hokkaido, Japan. October 7-9, 1996. Abstracts].

PMID- 8983226
TI  - [The regional meeting of the Otorhinolaryngological Society of Japan. Abstracts].

PMID- 8983227
TI  - [The regional meeting of the Otorhinolaryngological Society of Japan. Abstracts].

PMID- 8983228
TI  - [The 97th congress of the Japanese Society of Otolaryngology. Fukuoka, Japan. May
      23-25, 1996. Abstracts].

PMID- 8983230
TI  - [The 36th annual meeting of the Japan Society of Chest Diseases. Tochigi, Japan.
      April 3-5, 1996. abstracts].

PMID- 8983231
TI  - [The 93rd meeting of the Japanese Society of Internal Medicine. Yokohama, Japan.
      April 11-13, 1996. Abstracts].

PMID- 8983229
TI  - [The 39th annual meeting of the Japanese Society of Nephrology. Okayama, Japan.
      May 30-June 1, 1996. Abstracts].

PMID- 8983232
TI  - [The 69th general meeting of Japanese Leprosy Association. Okayama, Japan. April
      25-27, 1996. Abstracts].

PMID- 8983233
TI  - [The 69th annual meeting of the Japanese Society for Bacteriology. Fukuoka,
      Japan. March 27-29, 1996. Abstracts].

PMID- 8983234
TI  - APS Intersociety meeting. The Integrative Biology of Exercise. Vancouver, British
      Columbia, Canada, October 16-19, 1996. Abstracts.

PMID- 8983235
TI  - [XXXII National Congress of the Spanish Society of Cardiology. Tenerife, 28-31
      October 1996. Abstracts].

PMID- 8983236
TI  - [The 38th congress of the Japanese Society of Clinical Hematology. Omiya City,
      Saitama, Japan. November 13-15, 1996. Abstracts].

PMID- 8983237
TI  - Protein crystallization.
AB  - Crystallization is necessary to obtain the three-dimensional structure of
      proteins and nucleic acids; it often represents the bottleneck in structure
      determination. Our understanding of crystallization mechanisms is still
      incomplete. In this review, we emphasize fundamental aspects of the
      crystallization process. Protein-protein contacts in crystals are complex,
      involving a delicate balance of specific and nonspecific interactions. Depending
      on solution conditions, these interactions can lead to nucleation of crystals or
      to amorphous aggregation; this stage of crystallization has been successfully
      studied by light scattering. Post-nucleation crystal growth may proceed by
      mechanisms involving crystal defects or two-dimensional nucleation, as observed
      by atomic force and interference microscopy. Cessation of growth has been
      observed but remains incompletely understood. Impurities may play important roles
      during all stages of crystallization. Phase diagrams can guide optimization of
      conditions for nucleation and subsequent crystal growth; a theoretical
      understanding relating these to the intermolecular interactions is beginning to
      develop.

PMID- 8983238
TI  - [Apropos of drug allergy].
AB  - Immuno-biological diagnosis of allergies lo medicines can be carried out using a
      Flow Cytometer and by activating cells such as basophils and lymphocytes with
      membrane markers. A description is given of two cases of patients allergic to a
      myorelaxant: Rocuronium, who showed a correlation between the clinical history,
      skin tests and a positive basophil activation test, when compared to six negative
      controls.

PMID- 8983239
TI  - [Observatoire des Allergies Oculaires. National epidemiological survey of chronic
      (perennial) allergic conjunctivitis and/or keratoconjunctivitis seen in
      ophthalmology].
AB  - A second epidemiological ocular allergy survey was carried out by
      ophthalmologists during the winter of 94/95 in order to define the main
      characteristics of patients suffering from chronic, perennial allergic
      conjunctivitis or keratoconjunctivitis. From the data collected from a wide
      sample of 791 patients, we were able to describe the main symptoms and lesions
      related to chronic ocular allergy, its evolution and the allergens involved.
      Allergic symptoms (conjunctival redness, foreign body sensation, itching) are
      reported in 98.5% of patients. Non specific symptoms (burning, photophobia,
      blurred vision, ocular dryness) are reported in 3 patients out of 4. 40% of
      patients have perennial manifestations without any seasonal exacerbation while 1
      patient in 2 suffers from a seasonal worsening. In 80% of the cases, the
      responsible allergens are domestic (house dust, miles), 60% of patients are
      affected by at least 2 allergens. Ophthalmic examination shows lesions of the
      tarsal conjunctiva (papillas, follicles) in 94% of the cases and corneal lesions
      in practically 50% of the patients. This epidemiological survey shows the
      necessity of having a rigourous clinical approach which includes a complete
      ophthalmological examination which is the only thorough means of assessing the
      allergic lesions and proposing the most suitable treatment for day to day
      ophthalmic practice.

PMID- 8983240
TI  - [General considerations on asthma].
AB  - Asthma is an inflammatory illness of which the morbidity and mortality are on the
      increase. Its diagnosis is by clinical history, exploration of respiratory
      function, immuno-allergological investigation, skin tests and biological
      measurements that today are well-developed. Treatment of asthma must first fight
      the bronchial inflammation before a consideration of the etiological aspects. It
      uses inhaled corticosteroids (CSI), which is the step of etiological treatment,
      because of their good dose-efficacy properties. Bronchial penetration of CSI in
      an aerosol dose is often uncertain because of problems of hand-lung coordination.
      Beclojet 250, thanks to its Jet inhalation device, gives optimal broncho
      pulmonary penetration.

PMID- 8983241
TI  - [Brief update on bisulfite allergy].
AB  - The consumption of bisulphites is considerable in the general population as it is
      a preservative that is used both in foods and medications. Nevertheless,
      incidents or accidents of hypersensitivity are rare, but special attention must
      be given to subjects at risk: asthmatics and those who are allergic and
      intolerant to aspirin. The course to follow is to consider these three principal
      points: To watch for clinical signs that may precede more severe accidents. To
      recognize the responsibility of sulphites and detect the mechanism. Inform the
      patient of the need to avoid it as far as possible: any label that is coded with
      preservatives E 220 to E 227.

PMID- 8983242
TI  - Acid rain in Laos and Thailand.
AB  - Acid rain has an impact on forestry and human health. Forest degradation was
      noticed in the early 90's in Laos, a country without polluting industries nor
      intense automobile traffic. Therefore, in 1993-1994, we collected rain in one
      location in Thailand (Bangkok) and 4 in Laos (Luang Prabang, Vientiane,
      Savannaketh, Pakse); measured pH in each sample and resistivity in 2 locations.
      We obtained sequential meteorological satellite pictures showing the far motion
      of clouds, their location and course, and ultimately rain over Indochina. We
      conclude that acid rain forms over Thailand and falls in Laos (Vientiane, Pakse).
      We also measured peak flows in large groups of children, adults both non-smokers
      and chronic heavy smokers, in all five locations. Except for a small number of
      individual variations, we could not correlate the presence of acid rain and
      deterioration of pulmonary function in these subjects. However, we recommend
      active measures to curb pollution both in Thailand and Laos.

PMID- 8983243
TI  - [Dengue in Nicaragua, 1994: reintroduction of serotype 3 in the Americas].
AB  - The principal aim of this work was to report the reintroduction of dengue virus
      serotype 3 in the Americas after an absence of 17 years. In addition, it
      describes the most common symptoms associated with classical dengue and
      hemorrhagic dengue and presents data on the distribution of the epidemic in the
      various comprehensive local health care systems of Nicaragua. The study group
      consisted of 39 patients hospitalized in Managua and Leon for dengue with
      hemorrhagic manifestations and hemorrhagic dengue. Of these patients, 34 were
      classified as probable or confirmed cases of dengue. The most frequent symptoms
      were fever, headache, vomiting, and muscle and joint pains. The tourniquet test
      was positive and thrombocytopenia was confirmed in 56% and 44% of the patients,
      respectively. Epistaxis (67%) was the most common hemorrhagic sign. Of the 356
      serum samples received through the dengue surveillance systems in October 1994,
      IgM antibodies were detected in 43%. The virus was isolated from 5 of 24 samples
      tested (serotype 3 from 3 and serotype 1 from 2). The reintroduction of serotype
      3 of dengue into the Region was demonstrated, along with its ability to produce
      epidemics of hemorrhagic dengue. The countries are warned that if they do not
      quickly take the measures described in the guidelines for the prevention and
      control of dengue and dengue hemorrhagic fever, new epidemics may occur in the
      Americas, given the large number of persons susceptible to this serotype and the
      high density of the mosquito vector in most of the countries of the Region.

PMID- 8983246
TI  - Cell multiplication.

PMID- 8983244
TI  - [Liver cirrhosis in Brazil: mortality and productive years of life lost
      prematurely].
AB  - This descriptive study was done using official data on mortality from cirrhosis
      of the liver for the year 1989. Its objectives were: (a) to describe mortality
      from cirrhosis of the liver in Brazilian adults; (b) to estimate the productive
      years of life lost (PYLL) prematurely (between 20 and 59 years of age) from this
      cause; and (c) to identify any regional differences in mortality or PYLL. The
      crude data were adjusted by age and sex, using the 1980 population of Brazil as
      the standard. Calculation of PYLL was based on the formula of Romeder and
      McWhinnie for years of potential life lost, modified by the author to express
      productive years of life lost. The crude death rates were higher in the Southeast
      and North, and in all regions they were higher in males, the countrywide
      male/female ratio being 4.5. Mortality rates among males varied from 14.37 per
      100,000 in the Center-West to 35.86 per 100,000 in the Southeast; for females the
      rates ranged from 3.49 to 8.5 per 100,000 in the Center-West and North,
      respectively. The mortality curves by age for men showed a decline or
      stabilization after age 60, except in the North. For men in that region, the
      curve continued to rise, and the rate reached 86.37 per 100,000 after age 70. The
      curves for women also rose, most markedly in the North and Northeast. The age
      adjusted rates showed a reduction for women in the Southeast, while rates in the
      North remained higher. Mortality from cirrhosis of the liver accounted for 48.7%
      of deaths from disorders of the digestive system among men and 24.1% among women.
      Of the 138,860 PYLL from cirrhosis of the liver in 1989, 83.2% were lost among
      males, while the average for the country, around 15.5 years, was similar for both
      sexes. However, the average PYLL for men and women in the North and women in the
      Center-West was much higher than in the other regions. The data suggest that
      cirrhosis of the liver among men in all the regions, except the North, is
      probably attributable to alcoholism. Among males from the North, there is strong
      evidence that cirrhosis with a viral etiology (hepatitis B and C virus) also
      exists. For women, the evidence suggests that cirrhosis of viral etiology
      predominates.

PMID- 8983245
TI  - [Child and adolescent abuse: an international perspective].

PMID- 8983247
TI  - Cell differentiation.

PMID- 8983249
TI  - Vocational training: the end or the beginning?

PMID- 8983248
TI  - Unrecognized psychiatric illness in general practice.

PMID- 8983250
TI  - Evaluation of an educational programme to improve the recognition of
      psychological illness by general practitioners.
AB  - BACKGROUND: Take Care is a commercially sponsored educational package for the
      detection and management of depression by all members of the primary health-care
      team. AIM: This study was designed to evaluate whether the educational package
      affects the recognition of psychological illness by general practitioners.
      METHOD: General practitioners working in 13 practices in North West England or
      Trent Regional Health Authorities took part the evaluation. Patients who scored
      more than eight on the depression or anxiety component of the Hospital Anxiety
      and Depression (HAD) scales, and who were thought by their general practitioner
      to have a totally physical problem or no illness, were deemed to have a
      psychological illness that had been 'missed' by the doctor. Changes in the
      proportion of missed cases before and after exposure to Take Care were estimated.
      RESULTS: When all practices were considered together, the general practitioners
      missed a depressive illness in 24.1% of patients before Take Care, and 17.1%
      afterwards; absolute decrease 7.0% [95% confidence interval (CI) -2.0 to -12.0%].
      An improvement was seen in most practices (Wilcoxon matched-pair test P < 0.05).
      The programme was also associated with a small reduction in the overall
      proportion of episodes of anxiety missed by the doctor (absolute decrease 4.5%;
      95% CI -1.0 to -8.0%) a reduction was found in most practices (Wilcoxon matched
      pair test P < 0.05). There was no material difference in the diagnostic false
      positive rate of the doctors before and after the introduction of the programme.
      CONCLUSION: Exposure to an educational package for depression was associated with
      improved recognition of psychological illness by general practitioners.

PMID- 8983252
TI  - Stresses, coping mechanisms and job satisfaction in general practitioner
      registrars.
AB  - BACKGROUND: There is concern about the morale of general practitioner registrars.
      There may be stress-provoking factors that could be avoided or minimized. AIMS:
      The aims of the study were to assess the sources of stress and job satisfaction
      of general practitioner registrars, to compare registrars' job satisfaction with
      that of established principals using a recently published survey and to identify
      registrars' usual responses to stress. METHOD: A postal questionnaire survey was
      sent to all 143 general practitioner registrars in the West Midlands Region. The
      main measures were: self-rating scales of stresses associated with work and
      training; the Warr, Cook and Wall job satisfaction scale; and self-reported
      responses to stress. RESULTS: A total of 118 (83%) general practitioner
      registrars responded. The most potent sources of stress were family-job conflict,
      working for the Membership of the Royal College of General Practitioners,
      patients' unrealistic expectations and disruption of social life. Registrars
      practised good coping responses to stress. Registrars in this study had
      significantly greater job satisfaction than general practitioner principals in a
      1993 survey for three out of 10 items measured (responsibility given, hours of
      work and the job as a whole) and significantly worse scores for three items
      (recognition for good work, rate of pay and variety of work). CONCLUSIONS:
      Registrars have additional stresses to those of established principals because
      they need to study for examinations, learn new tasks in general practice and
      carry out their service commitments at a stage in life when many are newly
      married or have a young family. Training in stress management for general
      practitioner registrars is recommended.

PMID- 8983253
TI  - Perceptions of urinary symptoms and health-care-seeking behaviour amongst men
      aged 40-79 years.
AB  - BACKGROUND: Little is known about why men fail to seek medical help for
      urological symptoms. AIM: This study was designed to document men's perceptions
      of urinary symptoms and to increase understanding of health-care-seeking
      behaviour. METHOD: A stratified random sample of men aged 40-79 years was drawn
      from the age-sex register of a health centre in Central Scotland. Two hundred men
      were interviewed using semi-structured qualitative techniques and asked to
      complete a symptom questionnaire. The response rate was 65%. RESULTS: Urinary
      symptoms reported to be most bothersome were dribbling, hesitancy and straining.
      All but the youngest age group (40-49 years) associated developing urinary
      symptoms with ageing. This was considered to be a reason not to consult a doctor.
      Most symptoms were not thought to be serious. Pain, haematuria and acute
      retention gave cause for concern, and were perceived as reasons for seeking
      medical help. Although urinary symptoms interfered with selected activities in
      daily life, this was not a worry to the men and was not seen to be a sufficient
      reason alone to consult their general practitioner. CONCLUSION: The insidious
      development of urinary problems over time reinforces the belief that it is part
      of getting older and accounts for the accommodation of symptoms within men's
      everyday living experiences. Bothersomeness associated with urinary symptoms was
      not synonymous with worry or problems. Doctors must be prepared to initiate
      discussion about urinary function in order to assess the impact of symptoms on an
      individual's daily life.

PMID- 8983251
TI  - Continuing medical education in mental illness: a paradox for general
      practitioners.
AB  - BACKGROUND: In 1992, the Royal College of General Practitioners instituted its
      fellowship in mental health education, which aimed to provide general
      practitioner tutors with the skills they need to help general practitioners
      manage mental illness in general practice. However, the emphasis of the
      fellowship on pedagogic education may discourage educators wishing to introduce
      andragogic teaching, a paradox which general practitioners must resolve if the
      aims are to be realized. AIM: This study set out to follow the difficulties
      encountered by the regional fellows in managing the fellowship and to understand
      how the scheme has evolved. METHOD: Data collected for interim evaluation of the
      fellowship was studied and interviews undertaken with the senior fellow and the
      regional fellows participating in the scheme. RESULTS: From its beginnings, the
      project encountered difficulties involving acceptance among general practitioner
      tutors. In response to the objections raised, the project metamorphosed through
      three stages, from a (perceived) pedagogic approach to a much more overtly
      learner-centered one. CONCLUSION: Learner-centred education requires trust and
      belief in the ability of general practitioners to teach general practitioners;
      over-protection of the audience from 'non-expert' educators merely perpetuates
      the status quo. If education in mental health care is to become truly learner
      centred, general practitioners must address this paradox.

PMID- 8983254
TI  - Motivation of general practitioners attending postgraduate education.
AB  - BACKGROUND: The 1990 Contract encouraged general practitioners to participate in
      continuing medical education by providing a financial incentive. AIM: The study
      was designed: to determine the motivation of general practitioners attending
      education events; and to compare motivation and reasons for attendance pre- and
      post-Contract at commercial and non-commercial meetings, and at the different
      educational categories of Disease Management (DM), Health Promotion (HP) and
      Service Management (SM). METHOD: Two structured questionnaires were used. The
      first was sent to all general practitioners in the West of Scotland and asked
      about motivation pre-1990 Contract and the second, post-Contract, looked at
      motivation and reasons for attending a course as part of post course assessment.
      This latter was part of a much larger study evaluating continuing medical
      education. RESULTS: A total of 1161 practitioners responded to questionnaire I
      and 552 general practitioners attended 27 randomly selected postgraduate
      meetings. Finance was a motivator in 3.8% pre-Contract, and this increased to
      33.3% post-Contract and was the most commonly stated reason for attendance in
      81.3%. Financial incentive had the biggest influence on those attending HP
      sessions (91.5%), then SM (87.2%) and finally DM (78.6% (chi 2 = 8.68; P < or =
      0.013). It was also important to 73% attending drug-company-sponsored meetings
      compared with 83.7% going to non-commercial ones. Interest was a good motivator
      both pre- and post-Contract, but more so for DM than other categories and drug
      company as opposed to non-commercial meetings (chi 2 = 9.4; P < 0.002). Lack of
      knowledge became a less-important motivator post-Contract, and doctors felt least
      knowledgeable in SM (62.2%), as opposed to DM (57.9%) and HP (23.6%) (chi 2 =
      38.8; P < 0.001, with each differing significantly from both others). Doctors
      found the topics provided by the pharmaceutical companies more interesting (chi 2
      = 9.4; P < 0.002) and the hospitality provided more alluring than scheme meetings
      (chi 2 = 28.6; P < 0.001). CONCLUSIONS: Finance has a major effect on attendance
      at postgraduate meetings but may not be a good incentive for learning. Planning
      for education must take into account the different motivational factors for the
      different categories. Reasons for attending commercial meetings differ from non
      commercial ones and these events should be closely monitored.

PMID- 8983255
TI  - Comparison of amoxycillin and clarithromycin as initial treatment of community
      acquired lower respiratory tract infections.
AB  - BACKGROUND: Numerous new oral antibiotics have been produced over the last few
      years with the aims of improving treatment for lower respiratory tract
      infections. AIM: The aim of the study was to compare the efficacy of an
      established drug, amoxycillin, with a new macrolide, clarithromycin, for initial
      treatment of adults with community-acquired lower respiratory tract infection.
      METHOD: Consecutive adults fulfilling a standard definition of lower respiratory
      tract infection presenting to 14 general practitioners in two neighbouring
      practices were allocated to antibiotic therapy in a random, single-blind manner.
      The outcome of treatment was assessed by the time taken by the patient to return
      to normal activities or work, the speed of resolution of symptoms, number of
      repeat consultations and side effects. RESULTS: The profile of the 221 patients
      receiving amoxycillin was very similar to that of the 221 receiving
      clarithromycin. The two groups did not differ greatly in requirement to visit the
      general practitioner again within either 4 weeks (20% amoxycillin group; 25%
      clarithromycin group) or 3 months (31% compared with 36%) of the original
      infection, in time taken to return to normal activities (6 days for group taking
      amoxycillin; 5 days for those on clarithromycin) or work (5 days for both
      groups), or in speed of resolution of symptoms. Compliance was good and the side
      effects reported were similar for both groups. No increase in gastrointestinal
      complaints was noted for patients taking the macrolide. CONCLUSION: Amoxycillin
      and clarithromycin appear to be equally effective as initial therapy and to be
      tolerated in similar ways. Use of the newer drug appears to have no advantages
      over use of the accepted standard treatment.

PMID- 8983256
TI  - Medical students in general practice: how do patients feel?
AB  - BACKGROUND: The General Medical Council has recommended that medical students
      should gain more experience in general practice. AIM: The study set out to
      determine patients' reactions to the presence of medical students in general
      practice consultations. METHOD: Patients attending a random sample of general
      practice surgeries completed a questionnaire following consultation with and
      without a medical student present in six general practices in the Oxford area.
      RESULTS: The questionnaires were completed by 278 patients. Only eight (3%) of
      all respondents had negative responses to the presence of a medical student. Of
      those completing questionnaires following a teaching consultation, 107 (56%) felt
      positively about the presence of students, compared with 36 (41%) who had
      attended a nonteaching surgery. Only three patients (1%) felt the quality of the
      consultation to be impaired by the presence of a student, while 48 patients (17%)
      felt there to be some improvement. The majority felt that the sex of the student
      was unimportant, but significantly more female than male patients (17% versus 5%)
      felt that it made a difference. CONCLUSION: Only a small proportion of patients
      object to the presence of a medical student in general practice consultations. A
      significant minority said that the presence of a student improves the
      consultation.

PMID- 8983257
TI  - Prescription of antidepressants by general practitioners: recommendations by
      FHSAs and health boards.
AB  - BACKGROUND: In order to cut costs of prescribing by general practitioners family
      health service authorities (FHSAs) and health boards in the UK have been
      instructed to improve the quality and cost-effectiveness of prescribing by
      general practitioners in their area by tailoring advice to individual general
      practices. AIM: As over 95% of patients suffering from depression are treated by
      their general practitioner, a study was set up to investigate the effectiveness
      of the advice given by FHSAs and health boards to general practitioners on
      treatment of depression and prescription of antidepressant drugs. METHOD: The
      recommendations on prescription of antidepressants of professional advisors from
      all 117.FHSAs and health boards in the UK were elicited by telephone. Those who
      had produced written information for the general practitioners in their area
      regarding depression and antidepressants prescribing during the study period were
      asked to send a copy to the researchers. RESULTS: An excellent response rate
      (100%) was obtained to the telephone survey, and all of the bodies that provided
      their general practitioners with written information on depression and
      prescription of antidepressants sent in copies. Most of the documents received
      were informative and accurate; however, others provided information that was
      incorrect. CONCLUSION: Bulletins and newsletters from FHSAs and health boards are
      capable of influencing the prescribing patterns of general practitioners in their
      area, and must contain accurate and up-to-date information if they are to improve
      the management of depressed patients in the community.

PMID- 8983258
TI  - Epilepsy in general practice: patients' psychological symptoms and their
      perception of stigma.

PMID- 8983259
TI  - Who needs antiplatelet therapy?
AB  - A series of overviews or meta-analyses of randomized clinical trials prepared by
      the Antiplatelet Trialists' Collaboration were published in the British Medical
      Journal in January 1994. They demonstrated that prolonged courses of medium-dose
      aspirin were very effective at preventing both fatal and non-fatal myocardial
      infarction and stroke in patients at high risk of occlusive vascular disease. The
      aim of this review is to provide the general practitioner with a practical guide
      to the use of aspirin in patients at high and low risk of occlusive vascular
      disease and to discuss appropriate dosages and contraindications to treatment in
      the light of all the recent evidence.

PMID- 8983260
TI  - Heart failure in primary care.

PMID- 8983261
TI  - Heart failure in primary care.

PMID- 8983262
TI  - Medical audit in France.

PMID- 8983264
TI  - Hadrons in radiation therapy. Proceedings of the meeting of the European Heavy
      Particle Therapy Group. Orleans, France, 4-6 May 1995.

PMID- 8983263
TI  - [Costs of radiotherapy and patient transportation].

PMID- 8983266
TI  - Rheumatoid arthritis and lymphatic cancer.

PMID- 8983265
TI  - Detection of early micrometastases in malignant melanoma.

PMID- 8983267
TI  - Is isolated limb perfusion of metastatic malignant melanoma of the extremity
      worthwhile?

PMID- 8983268
TI  - Primary treatment in stage II non-seminomatous germ cell tumours of the testis: a
      matter of scalpel or drug infusion?
AB  - The optimal primary treatment of patients with low volume (< or = 5 cm)
      retroperitoneal metastases remains a matter of debate. Retroperitoneal lymph node
      dissection (RPLND) is a common practice in North America whereas chemotherapy is
      a prevailing approach in Europe. In patients with normal serum tumour markers
      after orchiectomy, primary RPLND appears to be the most appropriate way of
      staging. In other patients, neither surgery nor chemotherapy are entirely
      sufficient as monotherapy since approximately one-third of cases for each
      approach will need the other for achieving optimal results. Treatment decisions
      are based on cost/benefit and risk/benefit considerations, including relative
      toxicity and individual patient preference. The treatment of low volume stage II
      non-seminomatous germ cell tumours (NSGCT) clearly is a matter of scalpel and
      drug infusion.

PMID- 8983269
TI  - Early detection of familial ovarian cancer.
AB  - When ovarian cancer is detected at an early stage, prognosis is good, which has
      led to discussion of a screening programme. The aim of this study was to identify
      and examine women at high risk of familial ovarian cancer, and to evaluate the
      inclusion criteria and the diagnostic methods for early detection of ovarian
      cancer. We report the first round screening findings in a prospective study of
      180 women (mean age 43.4 years) considered to be at high risk of ovarian cancer
      based on family history. They were subjected to gynaecological examination with
      transvaginal ultrasound (TVU), CA125 and breast examination. Of these, 13 women
      with oestrogen receptor positive breast cancer had therapeutic oophorectomy and
      the ovaries were histologically examined. Among 180 women examined, nine ovarian
      cancers (among them two found at oophorectomy because of breast cancer) (mean age
      49.0 years), seven benign tumours of the ovary (mean age 48.1 years), one cancer
      of the cervix, and four breast cancers were diagnosed. The prevalence of ovarian
      cancers (5%) was significantly more than in any previous series. TVU as a
      diagnostic method proved useful and detected 7/9 cancers, whereas CA125 was
      elevated in 4/9 cancers. To our knowledge, this is the first programme which has
      successfully delineated a high risk group and prospectively demonstrated their
      high prevalence of ovarian cancer. Possible biases are discussed.

PMID- 8983270
TI  - Impact of scheduling on toxicity and clinical efficacy of doxorubicin: what do we
      know in the mid-nineties?

PMID- 8983271
TI  - Detection of early micrometastases in subcutaneous fat of primary malignant
      melanoma patients by identification of tyrosinase-mRNA.
AB  - To improve survival following melanoma excision, wide margin resection including
      subcutaneous fat, is indicated. Subcutaneous fat, resected with primary
      melanomas, was investigated using the tyrosinase PCR method originally described
      for detection of melanoma cells in peripheral blood. Identification of tyrosinase
      transcripts was possible in 4 melanoma patients (3 Clark level IV, 1 level III),
      while negative results were obtained from 6 other patients (2 level IV, 3 level
      III and 1 level I). In control experiments, after infiltration of the reference
      cell line SkMel into normal fat tissue, the PCR was positive in 33% (3/9) with
      10(2) infiltrated cells, 69% (9/13) with 10(4) cells and in 100% (7/7) with 10(6)
      cells. We conclude that detection of melanoma cells in subcutaneous fat tissue is
      possible by tyrosinase PCR. Follow-up studies should show whether such positive
      tyrosinase PCR can define patients at very high risk of tumour relapse.

PMID- 8983272
TI  - A single centre's 10 year experience with isolated limb perfusion in the
      treatment of recurrent malignant melanoma of the limb.
AB  - The aim of this study was to assess whether isolated limb perfusion can be
      performed safely and whether it offers improved disease-free survival for
      patients with limb malignant melanoma. Between August 1983 and July 1993, 103
      patients (78 female, 25 male) with recurrent limb melanoma were treated by
      isolated limb perfusion (ILP) in Glasgow, U.K. The mean age of the patients was
      62 years; 95 had leg recurrence, 8 had arm recurrence. The mean time from
      original diagnosis to ILP was 48 months (range 1-290). 102 iliac, 5 femoral, 7
      popliteal and 8 axillary perfusions were performed. All patients had stage II
      (local recurrence within 3 cm of primary site) or stage III (regional metastases;
      tissues excluding nodes, nodes or combination) disease according to the MD
      Anderson Cancer Centre Staging System. At a mean follow-up of 30.7 months, 68
      patients had died of recurrent disease (mean time to death 22.5 months). The 2
      and 5 year survival of the group was 50 and 26%, respectively and disease-free
      survival was 23 and 12%, respectively. At first perfusion, 76% of patients showed
      complete response and 23% showed partial response. With repeat perfusion, 47%
      showed complete response and 53% had partial response. In conclusion, ILP is safe
      and has an acceptable morbidity. It achieves highly satisfactory local disease
      control but long-term survival is the exception.

PMID- 8983273
TI  - Pain and discomfort during mammography.
AB  - The aim of this prospective study was to investigate associations of mammography
      pain and discomfort with sociodemographics, personal history and psychological
      and situational factors. Subjects were women with a negative screening finding (n
      = 883) from a random sample of 50-year-old Finnish women attending their first
      breast cancer screening. Questionnaires were sent 1 month before the screening
      invitation and 2 months after screening. Sixty-one per cent reported painful and
      59% uncomfortable mammograms (4% severely). Linear regression analyses showed
      that anticipation of pain and discomfort was the most powerful factor explaining
      pain and discomfort among women with earlier mammography. However, it had no
      effect among women without earlier mammography, for whom screening-related
      nervousness and perceptions of staff were crucial. Suggested interventions
      include better information before screening, a friendly screening atmosphere and
      empathetic, supportive staff behaviour, especially towards women having their
      first mammogram, encouraging them to feel more at ease and distracted from pain.

PMID- 8983274
TI  - Prognostic value of quantitative cytometry in a series of 415 T1T2/N0N1/M0 breast
      cancer patients--preliminary results.
AB  - Identifying prognostic markers in local regional breast carcinomas remains an
      important challenge today. DNA content obtained by flow cytometry, has been found
      to be of prognostic value; results with other methods remain less clear. This
      report describes DNA image cytometry patterns which are assessed with respect to
      disease-free survival. From June 1982 to December 1992, 415 patients under 75
      years of age, without any previous or synchronous carcinoma, suffering from an
      invasive breast cancer classified as T1 (52.8%), T2 (47.2%), N0 (65.1%) N1
      (34.9%), MO according to clinical TNM staging, were enrolled in this study. The
      median age was 53 (28-75) and 58.8% of the patients were premenopausal; 85.3%
      underwent a breast conservative procedure and 14.7% a modified radical mastectomy
      followed by postoperative irradiation. Histological axillary lymph node status,
      Scarff-Bloom grade and/or cytological grade and, oestrogen receptor content were
      used in decision-making for adjuvant treatment: hormonotherapy (48%) or
      chemotherapy (18.8%). Imprints were taken from the macroscopically visible lesion
      at the time of surgery, and a Feulgen staining was carried out on air dried
      smears to be analysed using the Samba 200 cell image processor (Alcatel TITN,
      France). Five parameters were systematically assessed: proliferation index; DNA
      histogram, integrated optical density, DNA malignancy grade, ploidy balance. With
      a median follow-up of 36 months (0-105), proliferation index (P = 0.0008), DNA
      histogram (P = 0.0017), integrated optical density (IOD) (P = 0.018) and DNA
      malignancy grade (P = 0.017) had a significant prognostic value on disease-free
      survival estimated by the Kaplan-Meier method. When these parameters were
      included in a Cox proportional regression hazards model, PR (P = 0.01), Scarff
      Bloom histological grading (P = 0.02), axillary clearance (P = 0.04) were
      significant; however, in the same model, taking into account the axillary lymph
      node histological status, IOD was significant for pN- patients (P = 0.03), and
      proliferation index (P = 0.03) was significant for pN+. Such results need to be
      updated with a longer median follow-up, but they suggest that the mean DNA
      content, as measured by the integrated optical density (IOD), should be
      considered when deciding on medical adjuvant treatment with respect to patients
      with a negative axillary clearance.

PMID- 8983275
TI  - Comparison of prognostic markers detected by immunohistochemistry in male and
      female breast carcinomas.
AB  - Male infiltrating breast carcinomas are rare and seem to have different
      characteristics, prognosis and sensitivity to hormonal treatment than those of
      female breast carcinomas. Our aim was to determine whether markers which have an
      established role in women are also important in men. 66 male infiltrating-ductal
      breast carcinomas were compared with 190 female breast carcinomas of the same
      type. Various markers were studied using immunohistochemistry. Tumour size at
      diagnosis, grade, number of axillary metastases and prognosis were comparable in
      male and female breast carcinomas. However, male breast carcinomas were
      characterised by a higher percentage of oestrogen receptor (OR) reactivity, and
      weekly associated with markers that, in women, are under oestrogen control. Male
      breast carcinomas were positive for markers under androgen control. Male breast
      carcinomas also differed from female carcinomas by the low percentage of p53+ and
      the high percentage of bcl-2+ tumours. The phenotype of male breast carcinomas
      has characteristics that could have repercussions on prognosis and on the choice
      of hormonal treatment. Only a few male breast cancers are p53+. OR, which are
      frequently present in male tumours, are probably not functional. In contrast,
      androgen receptors seem efficient, as several markers under androgen control are
      expressed. Therefore, the selection of hormonal therapy should not be based on OR
      status only.

PMID- 8983276
TI  - Large core biopsy for diagnostic and prognostic evaluation of invasive breast
      carcinomas.
AB  - Large core biopsy is a recently introduced method for pre-operative evaluation of
      breast lumps. The aim of this study was to evaluate the usefulness of this
      technique in providing pre-operative diagnostic and prognostic information that
      can lead to a correct line of treatment. We compared 41 cases of breast
      carcinomas diagnosed both by core biopsies and surgically removed samples. A high
      (93%) diagnostic agreement was obtained. Moreover, we found a significant
      correlation for mitotic count (r = 0.76), oestrogen receptor (r = 0.78),
      progesterone receptor (r = 0.80), p53 (r = 0.86) and c-erbB-2 (r = 0.90) analysis
      between core biopsy and definitive surgical pathology. An agreement for
      histological grading evaluation between the two techniques was obtained in 32 out
      of 40 cases (k = 0.65) whereas in the other cases, a lower grade was assigned by
      evaluating core biopsies. These findings suggest that percutaneous core breast
      biopsy is a valid tool for pre-operative management of breast lesions, but this
      should be confirmed in larger, prospective studies.

PMID- 8983277
TI  - Correlation between P450 CYP1A1 inducibility, MspI genotype and lung cancer
      incidence.
AB  - The aim of this study was to verify a possible correlation between CYP1A1
      induction, MspI genotype and lung cancer incidence. A case-control study was
      performed on 48 lung cancer patients and 81 healthy subjects to test the
      existence of a correlation, within a European population. The hyperinducible
      group exhibited a significantly higher risk of lung cancer (odds ratio = 3.41; P
      = 0.036), especially for adenocarcinoma (odds ratio = 5.29; P = 0.033). In
      contrast with the situation observed in Asian populations, the frequency of the
      M2 allele did not differ significantly in the total lung cancer population
      (7.82%) and the group of healthy subjects (10.71%). The median inducibility value
      was slightly higher among cancer patients with one or two M2 alleles than among
      patients homozygous for the wild-type allele (P = 0.09). However, the percentage
      of individuals possessing at least one mutated allele was not significantly
      higher among hyperinducible patients (37.5%) than among non-hyperinducible
      patients (16.0%). No significant correlation could be found between M2 allele and
      lung cancer or between M2 allele and CYP1A1 inducibility; the only positive
      correlation found was between CYP1A1 hyperinducibility and lung cancer incidence.
      Our observations do not support the view that the presence of the M2 allele at
      the MspI site of the CYP1A1 gene constitutes a significant lung cancer risk in
      Caucasians.

PMID- 8983278
TI  - Enhanced acute toxicity in oropharynx carcinoma treated with radiotherapy and
      concomitant cisplatin, 5-fluorouracil and mitomycin C.
AB  - The aim of this study was to establish the feasibility of giving concomitant
      radiotherapy and 3 cycles of chemotherapy with cisplatin (CDDP), 5-fluorouracil
      (5-FU) and mitomycin C (MMC) in locally advanced inoperable oropharyngeal cancer.
      From March 1990 to September 1993, 27 male patients (mean age 55 years) were
      included in this study. 3 patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9,
      T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1,
      T4N2: n = 2, T4N3: n = 1). All patients received conventional radiotherapy
      delivering 70 Gy in 35 fractions and 52 days, and three cycles of chemotherapy
      starting on day 1, 21 and 42 with CDDP 20 mg/m2 and 5-FU 400 mg/m2 day 1 to day
      4, and MMC 10 mg/m2 day 1. With a mean follow-up of 34 months (17-59), 10
      patients (37%) were alive and free of disease. Among the 17 other patients, 8
      died of cancer. Crude locoregional control rate was 78%, and probability of local
      control at 1 and 2 years was 85 and 80%, respectively. One- and 2-year survival
      rates were 48 and 31%, respectively, for both overall and disease-free survival.
      Grade 3 or 4 mucositis occurred in 22 patients (81%); enteral feeding was
      necessary for 63%; mean weight loss was 5.7 kg. Grade > 2 thrombocytopenia
      occurred in 11 patients (41%), grade > 2 neutropenia in 8 patients (29%), grade >
      2 anaemia in 4 patients (15%). Febrile neutropenia or aplasia occurred in 5
      patients (19%). 2 patients (7%) died during treatment of haematological or
      infectious complications related to the treatment. Another patient died 1 month
      after treatment with grade 4 thrombocytopenia and septicaemia. In conclusion, a
      high complete response rate has been achieved with this concomitant chemo- and
      radiotherapy, but with severe digestive and haematological toxicity. Addition of
      MMC to 5-FU and CDDP might have been responsible for this increased toxicity.
      This therapeutic combination is therefore not routinely feasible.

PMID- 8983279
TI  - Phase II trial of intravenous endotoxin in patients with colorectal and non-small
      cell lung cancer.
AB  - We report the immunological and clinical results of a phase II trial with
      intravenously administered highly purified endotoxin (Salmonella abortus equi) in
      patients with advanced cancer. 15 patients with non-small cell lung cancer and 27
      with colorectal cancer were entered into the study. 37 evaluable patients
      received at least four injections of endotoxin (4 ng/kg body weight) and 1600 mg
      ibuprofen orally in 2-week intervals. Transient renal (WHO grade 0-1) and hepatic
      (WHO grade 0-4) toxicities occurred in several patients. Constitutional side
      effects such as fever, chills and hypotension could not be prevented completely
      by pretreatment with ibuprofen. 3 patients in the colorectal cancer group
      demonstrated objective responses (1 complete remission (CR), 2 partial remission
      (PR)). The complete remission has been maintained for more than 3 years, while
      the partial remissions were stable for 7 and 8 months, respectively. Only
      marginal antitumour effects were seen in the lung cancer group. Tolerance of the
      macrophage system to the stimulatory effect of endotoxin, as measured by human
      necrosis factor alpha (TNF-alpha) release into serum, built up after the first
      administration and remained at a steady-state level after each subsequent
      injection. In constrast, rising CD4:CD8 ratio and release of tumour necrosis
      factor beta (TNF-beta) indicated the continuing activation of the lymphocyte
      system by repetitive injections of endotoxin.

PMID- 8983280
TI  - Double biochemical modulation of 5-fluorouracil by methotrexate and levo-folinic
      acid in the treatment of advanced digestive tract malignancies.
AB  - The aim of this study was to evaluate the activity and toxicity of a double
      biochemical modulation of 5-fluorouracil (5-FU) by means of methotrexate (MTX)
      and levo-folinic acid (LFA) in patients with advanced carcinoma of the digestive
      tract, and to assess the prognostic significance of MTX serum concentrations
      achieved in these patients. 94 patients affected by advanced carcinoma of the
      colon-rectum, stomach or biliary tract (47 of them previously untreated) received
      a regimen consisting of MTX 500 mg/m2 as a 2-h i.v. infusion on day 1, followed
      by LFA 250 mg/m2 as a 2-h i.v. infusion and 5-FU 600 mg/m2 as an i.v. bolus on
      day 2. Cycles were repeated every 2 weeks. Treatment was administered until
      tumour progression or for a maximum of 24 courses. MTX serum level was assessed
      soon after and 24 h (24-h MTXs) after its infusion in 61 patients. One complete
      and 22 partial responses were obtained, giving an overall activity of 24% (95%
      confidence interval, 16-34%). Response rate was 30% in chemotherapy-naive
      patients (colorectal, 26%; gastric, 37%; and biliary-tract, 22%) and 19% in those
      previously treated (all with fluoropyrimidines). A poor performance status
      adversely affected the response and survival of patients. The toxicity of
      treatment was very mild, and occurrence of severe diarrhoea (11% of patients) and
      mucositis (3%) was lower than that reported with other modulations of 5-FU. A cut
      off value of 24-h MTXs was identified as a strong prognostic indicator. Patients
      with 24-h MTXs > or = 2 microM had a significantly better probability of response
      (37% versus 5%; P = 0.032), longer progression-free survival (5.3 versus 2.3
      months; P = 0.023) and overall survival (10.8 versus 8.3 months; P = 0.045) on
      multivariate analysis. In chemotherapy-naive colorectal cancer patients, those
      with 24-h MTXs > or = 2 microM had a response rate of 38% (3/8), with a 19.6
      month median survival time, as compared to no responses (0/4) and a 9.9-month
      median survival in the group with a lower serum concentration. The achievement of
      such MTX serum levels yielded a 31% (4/13) response rate even in colorectal
      patients who had previously received a 5-FU-FA treatment.

PMID- 8983281
TI  - Patterns of failure following treatment of pseudomyxoma peritonei of appendiceal
      origin.
AB  - Pseudomyxoma peritonei is a rare disease caused by a perforated adenoma of the
      appendix. It results in extensive accumulation of mucinous tumour at specific
      locations within the abdomen and pelvis. The study was undertaken to examine
      patterns of recurrence in patients with grade I disease treated by cytoreductive
      surgery and early postoperative intraperitoneal chemotherapy. After a median
      follow-up of 1.9 years (range 0.5-7.4 years) 42 out of 118 patients had recurred.
      In 32 patients, detailed information regarding the anatomical location of
      recurrent tumour from CT-scan and second-look laparotomy were available and these
      form the basis of this study. The volume of recurrent tumour was recorded at
      eight abdominal sites, the laparotomy scar and at suture lines. Patient, tumour
      and treatment factors were analysed for possible relationship with the pattern of
      recurrence. With recurrence, true metastatic disease was observed in 3 patients
      and a distinctly higher grade of intraperitoneal tumour in another patient.
      Pleural spread of pseudomyxoma was found in 6 patients, always related to
      entering the pleural cavity during cytoreduction (P = 0.000031). Two abdominal
      sites consistently had an increase in tumour deposits at re-operation as compared
      to the initial cytoreduction. Small bowel had large deposits at re-operation in
      17% versus 3% at initial cytoreduction and retroperitoneal surfaces 10% versus
      0%. Recurrences were most frequent in the left subhepatic/lesser omentum area
      (28%), while the right subdiaphragmatic area (3%) was least involved.
      Pseudomyxoma peritonei recurrence in the laparotomy scar was found in 15/29
      patients (52%), significantly more frequent if tumour had been present at former
      laparotomy scars during cytoreduction (P = 0.042). In 15/25 (60%) of patients,
      recurrences were found at suture lines. Differences in the completeness of
      cytoreduction, inadequate distribution of intraperitoneal chemotherapy to upper
      abdominal and small bowel surfaces, and entrapment of tumour within suture lines
      were thought to be causal factors consistent with this pattern of recurrence.
      Consequences for future treatment strategies are discussed.

PMID- 8983282
TI  - Evaluation of a prediction model of cisplatin dose based on total platinum plasma
      concentration.
AB  - The aim of this study was to validate prospectively a model of cisplatin dose
      adjustment. 27 patients (63 courses) with lung cancer were treated by a 5 day
      continuous infusion of cisplatin and etoposide. The dose of cisplatin was
      adjusted in order to reach a target plasma concentration of total platinum (TP)
      of 2000 mu/l at the end of the infusion. The target concentration was reached
      with a mean bias of 2.7% and a precision of 7.8%. The results were compared with
      those of a population of 38 patients (97 courses) with lung cancer and treated
      with the same protocol of chemotherapy, but without dose adjustment. The average
      dose adjustment was an increase of cisplatin dose of 20.2%. This augmentation was
      most important during the first course, decreasing during the following courses.
      There was also an increase in the etoposide AUC, although its dose was not
      modified. Toxicity to polymorphonuclear cells was significantly increased and was
      linked to etoposide AUC.

PMID- 8983283
TI  - Randomised comparison of ceftazidime and imipenem as initial monotherapy for
      febrile episodes in neutropenic cancer patients.
AB  - With the availability of new, broad-spectrum antibiotics, initial therapy with a
      single agent has become an alternative to classic combinations in the management
      of febrile, neutropenic cancer patients. The aims of this study were to compare
      the efficacy of ceftazidime and imipenem as empirical monotherapy of febrile
      episodes in neutropenic patients, and to examine the frequency with which second
      line antibiotics (amikacin, vancomycin, or both) were required. A prospective
      clinical trial was carried out in a single centre. Eligible patients with solid
      tumours or lymphoma were randomised to receive monotherapy with ceftazidime or
      imipenem. In the event of no response, amikacin and/or vancomycin were added in
      48-72 h intervals (sequentially, or according to clinical or microbiological
      data). Efficacy was evaluable for 111 assessable episodes. Median neutrophil
      count at entry was 100 cells/microliters and median duration of neutropenia was 4
      days. Febrile episodes were classified as microbiologically (34%) or clinically
      documented (42%), and fever of unknown origin (24%). Gram-negative infections
      (57%) predominated over gram-positive isolates (30%). The overall success rate
      with monotherapy (69% versus 70%), or with modification (20% versus 23%) were
      equivalent for ceftazidime and imipenem (P = 0.75). The mortality in this series
      was 5%. Single-agent therapy with either ceftazidime or imipenem is effective for
      the empirical treatment of febrile episodes in neutropenic patients with solid
      tumours. Early addition of amikacin and/or vancomycin resolves most failures of
      the first step.

PMID- 8983284
TI  - An increased loading dose of ondansetron: a north european, double-blind
      randomised study in children, comparing 5 mg/m2 with 10 mg/m2.
AB  - A North European, randomised, double-blind study, comparing a loading-dose of
      ondansetron of 5 mg/m2 with 10 mg/m2, administered intravenously before highly
      emetogenic chemotherapy, was carried out in 187 chemotherapy-naive children. In
      the first 24 h, both groups received further ondansetron intravenously at a dose
      of 5 mg/m2 8-hourly. Thereafter, ondansetron was given at an oral dose of 4 or 8
      mg depending on the surface area of the child, three times a day and continued
      for at least 3 days after the last day of chemotherapy. There was no difference
      in the control of emesis between the two groups. Ondansetron provided good
      control of emesis and nausea on day 1 with 71-72% of patients experiencing two or
      fewer emetic episodes (complete or major responders) and 90-86% of patients
      reporting nausea as none or mild. There was also no difference in the efficacy of
      the treatment arms in the control of emesis and nausea on subsequent days of the
      study period. Both anti-emetic regimens were well-tolerated.

PMID- 8983285
TI  - Constitutional nonsense germline mutations in the RB1 gene detected in patients
      with early onset unilateral retinoblastoma.
AB  - The 'two-hit' hypothesis for the development of the childhood eye cancer,
      retinoblastoma (Rb), predicts that bilaterally affected individuals will carry
      germline mutations. The second suggestion is that patients with early
      presentation of unilateral tumours also carry predisposing mutations. We have
      used SSCP analysis to study the 27 individual exons of the RB1 gene in
      constitutional DNA from 3 patients whose tumours were treated under the age of 12
      months. Bandshifts on SSCP gels were detected in 2 of these patients which, on
      sequencing, were shown to be a C-->T transition converting a CGAarg to a TGAstop
      codon in exon 17 and an 8 bp deletion in exon 20 resulting in a downstream stop
      codon. The mutations seen in these patients are reminiscent of those seen in
      patients with hereditary Rb and confirms that at least some early onset
      unilateral cases carry constitutional mutations, which has important implications
      for genetic screening and counselling of these individuals.

PMID- 8983286
TI  - Rheumatoid arthritis and cancer risk.
AB  - The aim of this study was to examine the cancer pattern in a large group of
      patients with rheumatoid arthritis (RA). A follow-up study of cancer incidence in
      RA was conducted within a cohort of 20,699 patients recorded in the Danish
      Hospital Discharge Register during 1977-1987 by linkage with the Danish Cancer
      Registry through 1991. There were consistent excesses of non-Hodgkin's lymphoma
      and Hodgkin's disease in both sexes and during both early and late periods of
      follow-up. Risks for lung cancer and non-melanoma skin cancer were also
      increased, with no predilection for any specific histological subtype, while
      risks for colorectal cancer and female breast cancer were reduced. The cancer
      pattern seen among Danish RA patients largely supports findings from two earlier
      Nordic investigations. Thus, there seem to be consistent positive associations
      between RA and non-Hodgkin's lymphoma, Hodgkin's disease and lung cancer and a
      consistent negative association with colorectal cancer.

PMID- 8983287
TI  - Adaptation of the cellscan technique for the SCM test in breast cancer.
AB  - The value of the SCM (Structuredness of Cytoplasmic Matrix) cancer test, a
      procedure based on the detection of differences in lymphocyte activation in the
      presence and absence of cancer, has remained controversial, with inconsistent
      results having been reported among investigators. The Cellscan, a high-precision
      static cytometer system, has been designed to perform the SCM test; the apparatus
      facilitates the polarisation measurements and can examine cells which have been
      separated by simpler procedures than were originally described. In this study,
      using methods and diagnostic criteria adapted for the Cellscan system in a
      hospital environment, the SCM test correctly classified over 90% (76/80) of
      patients with breast cancer and differentiated over 90% (72/73) of individuals
      without cancer.

PMID- 8983288
TI  - Fludarabine as a modulator of cisplatin activity in human tumour primary cultures
      and established cell lines.
AB  - The potential of the purine analogue fludarabine (9-beta-D-arabinofuranosyl-2
      fluoroadenine-5' monophosphate) as a modulator of cisplatin cytotoxicity was
      investigated in four established cell lines and 20 primary cultures of human
      melanoma and ovarian cancer. Tumour cells were exposed to fludarabine and
      cisplatin, alone or in combination, for 4 h. Fludarabine did not affect the
      growth of ovarian cancer cell lines, whereas it induced a marked and dose
      dependent inhibition of proliferation in melanoma cell lines. In primary cultures
      of both histotypes, the purine analogue did not induce appreciable
      antiproliferative effects. Combined cisplatin-fludarabine treatment caused
      additive effects in all established cell lines. Conversely, a synergistic effect
      of the combination was seen in 5 of 10 melanoma and 4 of 10 ovarian cancer
      primary cultures, with a dose-modifying factor ranging from 2.1 to 3.9 for
      melanomas and from 4.0 to 7.5 for ovarian cancers, respectively. In the remaining
      cultures, the interaction between fludarabine and cisplatin was additive. The
      alkaline filter elution analysis performed on primary cultures showed that the
      synergistic interaction between the two drugs was paralleled by an increase in
      the extent and persistence of the cisplatin-induced DNA interstrand crosslinks.
      Our results indicate that fludarabine can enhance cisplatin cytotoxic activity in
      human tumour primary cultures from ovarian cancer and malignant melanoma. Such an
      effect may be partially due to an interference by fludarabine on cisplatin
      induced DNA adduct metabolism and repair.

PMID- 8983289
TI  - Improved efficacy of chemotherapy by parvovirus-mediated sensitisation of human
      tumour cells.
AB  - Increasing resistance of tumour cells towards the cytotoxic action of
      chemotherapeutic drugs is a major limitation in the treatment of cancer patients.
      The non-pathogenic human adeno-associated viruses (AAV) have been reported to
      sensitise HeLa cervical cancer cells to gamma irradiation in vivo and in vitro.
      To test whether these parvoviruses might render other human tumour cells more
      sensitive towards chemotherapeutic drugs, we analysed the effects of AAV type 2
      (AAV-2) infection on established cancer cell lines and freshly explanted tumour
      biopsies treated with chemotherapeutic agents (e.g. cisplatin). AAV-2 infection
      significantly increased the cytotoxic activity of chemotherapeutic drugs compared
      with uninfected controls. AAV-2 infection without concomitant chemotherapeutic
      treatment had no significant effect on viability of the cells. In nude mice,
      combined application of AAV-2 infection and chemotherapeutic treatment
      significantly increased the therapeutic activity on tumours arising from
      subcutaneously injected tumour cells compared with tumours treated by
      chemotherapeutics only. These results indicate that AAV-2 infection sensitises
      human cancer cells towards the cytotoxic action of chemotherapeutic drugs.

PMID- 8983290
TI  - High molecular weight phospholipase A2 and fatty acids in human colon tumours and
      associated normal tissue.
AB  - Human colon tumours usually form more prostaglandins (PGs) than associated normal
      tissues, but the mechanism(s) are not fully understood. We analysed fatty acid
      compositions, in particular arachidonate, and measured the amount and the
      activity of high molecular weight cytoplasmic phospholipase A2 (cPLA2) of these
      tissues. Total lipids extracted from homogenised surgical specimens were
      transesterified and fatty acids were analysed by gas chromatography. cPLA2 was
      separated by SDS-PAGE, Western-blotted, immunoblotted using a specific antibody
      to cPLA2 and semiquantified following enhanced chemiluminescence using a scanning
      densitometer. cPLA2 biological activity was also assayed using 1-stearoyl, 2-[1
      14C]-arachidonyl, L-3-phosphatidylcholine. Compared with normal mucosa/submucosa,
      there was more total arachidonate in tumours (P < 0.01), and increased levels of
      cPLA2 occurred in 6 of 17 tumours. In conclusion, the higher amounts of tumour
      total arachidonate and the sometimes higher levels of cPLA2, might help to
      explain why some human colon tumours form increased amounts of PGs.

PMID- 8983292
TI  - Allele loss on chromosome 11q and microsatellite instability in malignant
      melanoma.
AB  - Loss of heterozygosity (allele loss, LOH) occurs frequently on the long arm of
      chromosome 11 in several types of cancer. We analysed 32 melanomas (almost all
      metastatic lesions) for allele loss at eight loci along the length of chromosome
      11 (ptel-D11S922-D11S899-D11S1324-D11S1313-++ +D11S901-NCAM-D11S29-D11S968-qtel).
      The highest frequency of loss (38%) was at D11S29 (11q23.3). Of 13 melanomas
      which had lost an allele at one or more loci, all but one showed LOH at either
      D11S29 or NCAM (11q22). The region between these two loci is the most likely
      location of any tumour suppressor gene. Low frequencies of LOH occurred on 11p
      and there was little evidence for tumour suppressor loci outside the 11cen-q23.3
      region. Unusually for melanomas, widespread microsatellite instability, with
      slippage of several repeat units, was observed in two of 32 tumours studied (and
      four other tumours showed new microsatellite alleles that differed by just one
      repeat unit from their normal counterparts). However, no mutations of the
      mismatch repair genes hMSH2 and hMLH1 were detected in these two tumours, and the
      observed replication errors may result from mutations in other genes involved in
      mismatch repair or DNA replication. LOH on 11q and replication errors appear to
      comprise part of the genetic pathways of several tumour types, including
      melanomas.

PMID- 8983291
TI  - Alteration in mucin gene expression and biological properties of HT29 colon
      cancer cell subpopulations.
AB  - Previous studies from our laboratory have shown that HT29 cells selected by
      adaptation to methotrexate (HT29-MTX) express mature mucins that differ in their
      immunoreactivity to antibodies against gastric mucin and in the level of one of
      two major gastric mucin MUC5AC (MUC5) mRNA compared with parental HT29 cells. In
      this study, we examined the expression of another major gastric mucin, MUC6 mRNA,
      as well as that of MUC2, -3 and -5 mRNAs in HT29-MTX cells. We also examined
      their relationship to mucin-related antigen expression and biological properties
      of the cells such as adhesion to matrigel and E-selectin and in vitro
      invasiveness, liver colonising activity and degree of differentiation of nude
      mouse xenograft. Slot blot and Northern analysis revealed markedly increased
      levels of MUC5 mRNA but no change in MUC6 mRNA level in HT29-MTX cells compared
      with parental HT29 cells which express barely detectable levels of MUC6 mRNA. A
      nuclear run-on study showed that MUC5 mRNA was up-regulated at the
      transcriptional level. The marked increase in MUC5 mRNA was associated with a
      significant increase in the expression of human gastric mucin and apomucin
      antigens in HT29-MTX cells. When the adhesive capacity of two cell lines was
      compared, HT29-MTX cells showed significantly lower adhesion to E-selectin
      consistent with their lower expression of sialyl Le(x) and sialyl Le(a) antigens
      compared with HT29 cells. HT29-MTX cells also showed lower adhesive capacity to
      matrigel than HT29 cells. Interestingly, HT29-MTX cells exhibited significantly
      decreased liver colonisation capacity in nude mice following splenic vein
      injection. Furthermore, nude mouse xenograft tumours produced by HT29-MTX cells
      exhibited a significantly greater degree of differentiation, consisting of mucin
      secreting glands than those produced by HT29 cells. In conclusion, these results
      indicate a shift of predominantly colonic-type mucins to the gastric type,
      specifically the surface epithelial cell type (MUC5) but not the mucous neck cell
      or antral gland type (MUC6) in HT29-MTX cells and strongly suggest that altered
      regulation of mucin genes and the degree of differentiation in cancer cells may
      be responsible for the altered biological behaviour of these cells.

PMID- 8983293
TI  - Effects of chronic administration of N-(4-hydroxyphenyl)retinamide (4-HPR) in
      rats on vitamin A metabolism in the eye.
AB  - The retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) effectively inhibits cancer in
      a variety of tissues. In contrast to many other retinoids, the toxicity problems
      associated with administration of 4-HPR have been found to be minimal or absent.
      However, the effects of 4-HPR upon normal metabolism of native physiological
      forms of vitamin A in vivo have not been adequately investigated. To understand
      better the interaction between 4-HPR and the native physiological forms of
      vitamin A, the present study examines the effects of long-term administration of
      4-HPR upon normal vitamin A metabolism in the eyes. Male Sprague-Dawley rats were
      fed either a control diet sufficient in vitamin A (CON group; 0.8 retinol
      equivalents [RE]/g diet; n = 28) or a CON diet supplemented with 4-HPR (CON + 4
      HPR group; 1173 micrograms 4-HPR/g diet; n = 28). Following an i.v. dose of
      physiologically radiolabelled retinol, associated with its normal plasma
      transport complex, the vitamin A content and radioactivity of the plasma and eyes
      were examined at different times over a 41 day period. Mean plasma retinol levels
      measured during the study period were significantly reduced in the CON + 4-HPR
      group as compared with the CON group (23.5 +/- 7.0 and 50.3 +/- 5.3 [mean +/-
      S.D.] micrograms/dl, respectively). From approximately 7 days post-dosing,
      vitamin A levels in the eyes of the 4-HPR-treated group steadily decreased such
      that by the end of the study, they were only approximately one-fifth those of the
      CON group (0.098 +/- 0.075 and 0.50 +/- 0.053 RE, respectively). Kinetic analysis
      of vitamin A turnover in the eyes indicated that there was no apparent down
      regulation of the fraction of vitamin A leaving this tissue on a daily basis;
      these values were found to be similar in both groups, averaging 0.104 +/- 0.0393
      and 0.113 +/- 0.0373 per day (mean +/- fractional standard deviation [F.S.D.])
      for the CON and CON + 4-HPR groups, respectively. At the same time, the flow of
      vitamin A through the eyes was significantly decreased in the CON + 4-HPR group
      eyes (0.0162 +/- 0.101 microgram/day) as compared with the CON group (0.0604 +/-
      0.0672 micrograms/day). Our results suggest that compensatory mechanisms that
      would normally function to conserve depleting ocular vitamin A stores may be
      blocked in the 4-HPR-treated animals and further, that the 4-HPR itself appears
      to be interfering with the normal uptake and/or metabolism of vitamin A in the
      eye. These findings may help to provide at least a partial explanation for the
      visual impairment problems that have been reported in human trials that include
      long-term administration of 4-HPR.

PMID- 8983294
TI  - Vinorelbine treatment of advanced non-small cell lung cancer with special
      emphasis on elderly patients.
AB  - The aim of this study was to investigate the activity and the toxicity of
      vinorelbine (VNB) in a population of patients with locally advanced inoperable or
      metastatic non-small cell lung cancer (NSCLC) including elderly patients unfit
      for cisplatin-based chemotherapy. VNB was administered at a dose of 25-30 mg/m2,
      intravenously, weekly until progression. Of the 83 patients who entered the study
      (median age 63 years, number of patients aged > or = 70 years = 23, median
      performance status = 80, stage IV in 58 patients, previous chemotherapy in 15
      patients), 76 were evaluable. One complete remission and 22 partial remissions
      were noted (30.2% response rate). Toxicity was mild. Median survival was 9
      months. No effect of age upon outcome was detected. Thus, single agent VNB is a
      reasonable option for advanced NSCLC, particularly in elderly patients.

PMID- 8983295
TI  - Soft tissue sarcomas in HIV-infected adult patients.
AB  - Clinical and biological features of three HIV-infected adults with soft tissue
      sarcoma are reported. Epstein-Barr Virus (EBV) detection was negative using in
      situ hybridisation, PCR analysis and Southern blot analysis in the two cases for
      which tumour samples were available, contrary to all previously reported
      paediatric cases. All three patients developed metastases. Chemotherapy was
      feasible but only afforded tumour stabilisation. The cause of death in all three
      cases was distant spread and not AIDS. Soft tissue sarcoma associated with HIV
      infection are not exclusively found in children, do not appear to be EBV-related
      in adult patients, and fare dismally despite vigorous therapy.

PMID- 8983296
TI  - Modulation of toxicity following external beam irradiation preceded by high-dose
      rate brachytherapy in inoperable oesophageal cancer.
AB  - To induce fast relief of dysphagia in inoperable oesophageal cancer, we applied
      high-dose rate (HDR) intraluminal irradiation followed by external irradiation
      (EBRT) in a phase II study. 15 patients (group A: n = 15; 10 men, 5 women; median
      age 66 years) were treated with 10 Gy HDR brachytherapy plus 40 Gy EBRT (15
      fractions of 2.67 Gy). Severe side-effects were encountered in 60% of patients: 3
      late ulceration, 2 pending fistula, 2 fistula and 2 patients with fatal
      haemorrhage after an interval of 6 months. Overall response was excellent: 9
      complete remissions (60%) and 6 partial responses (40%). Because of the high
      toxicity rate, in a subsequent study (group B: n = 30; 23 men, 7 women; median
      age 66 years) the EBRT scheme was changed using smaller fractions (2.0 Gy) to
      reach the same total dose of 40 Gy. The complication rate (17%) was significantly
      reduced, while the overall response remained excellent (83%): 17 complete and 8
      partial responses. The impressive change in complication rate of HDR
      brachytherapy and EBRT stresses the impact of the fraction per dose and
      illustrates the small therapeutic margins.

PMID- 8983297
TI  - Type C hepatitis and chronic lymphocytic leukaemia.

PMID- 8983298
TI  - Angiosarcoma of the breast after conservative surgery and radiation therapy for
      breast carcinoma: three new cases.

PMID- 8983300
TI  - Single agent paclitaxel in the treatment of unresectable and/or metastatic
      pancreatic adenocarcinoma.

PMID- 8983299
TI  - Severe cutaneous reactions following interferon injections.

PMID- 8983301
TI  - Serum neuron-specific enolase (NSE) as a tumour marker for the Ewing's sarcoma
      family of tumours.

PMID- 8983302
TI  - Transaxillary access to perform hepatic artery infusion (HAI) for secondary or
      primitive hepatic tumours.

PMID- 8983304
TI  - [Endorectal echography. Its usefulness in the study of neoplasms of the rectum].
AB  - OBJECTIVE: To analyze prospectively the results of the first endorectal
      ultrasonographies performed at the Coloproctology Unit of the Hospital Mutua de
      Terrassa in patients with rectal tumors. METHODS: During the period between
      September 94 to June 95, 27 endorectal ultrasonographies were performed to
      patients with rectal tumors. The echographies were performed with a 360 degrees
      transducer. The ultrasound findings were compared to the histological results.
      RESULTS: Three patients were not treated surgically, and were excluded from the
      analysis. In addition, three patients with perianastomotic recurrence were
      excluded. Of the remaining 21 patients the level of penetration in the rectal
      wall was correctly identified in 17 (81%). The presence of metastatic nodes was
      correctly assessed in 19 of the 24 patients explored (78%). CONCLUSION: For the
      preoperative assessment of rectal tumors, endorectal ultrasonography offers a
      good accuracy even during the learning curve.

PMID- 8983303
TI  - [Colorectal metachronous tumors].
AB  - INTRODUCTION: The metachronous colorectal carcinoma is defined as a primary
      carcinoma which arises after surgical removal of a previous carcinoma of the
      large bowel. The incidence of metachronous colorectal cancer has been reported to
      be 1-8 per cent. THE AIM: The purpose of the present study was to determine the
      incidence of metachronous colorectal carcinoma and, on this basis, to propose a
      follow-up programme after primary resection for cure in this patient group of
      patients. PATIENTS AND METHODS: Twenty-eight patients with metachronous
      colorectal malignancies underwent surgery, 16 (57.1%) male and 12 (42.9%) female.
      These metachronous cancers were discovered at intervals ranging from eight months
      to seven years (range 28 +/- 10 months). Nine (32%) metachronous lesions were
      detected two years of more after the original cancer. Six of the metachronous
      cancers appeared in the right colon, eight were distributed throughout the
      transverse and descending colon, and fourteen in the rectosigmoid region.
      Histological examination revealed a high proportion of early stage lesions (82.1%
      Duke's A more B). CONCLUSION: A set of patients surviving their initial
      colorectal cancer should be followed for the rest of their life because of the
      risk of developing a second primary. In the light of our experience, a full
      examination of the colon in these patients is mandatory, and colonoscopy is the
      best diagnostic procedure.

PMID- 8983305
TI  - [Treatment of acute colorectal obstructions by implantation of expandable metal
      prosthesis].
AB  - PURPOSE: To determine the efficacy of colorectal stents implanted through the
      anus for the treatment of acute intestinal occlusion before elective surgery.
      MATERIAL AND METHODS: 25 patients (3 females and 22 males) with a mean age of
      62.5 years (range: 49-94), were diagnosed of lower intestinal occlusion due to
      neoplasm. In all cases, an expandable metallic stent was implanted through the
      anus during the first 24 h. X-ray studies, tumoral staging and surgical
      preparation were performed in all cases. RESULTS: Implantation of stent was
      successful in 23 patients (92%). Clinical improvement of intestinal occlusion was
      observed in 24 hours. Criteria of no-resectability were found in five patients
      (20%). The remaining patients (18 cases) were treated by tumoral resection and
      end-to-end anastomosis an average of 8.6 days there after. No complications were
      observed and the patients were discharged 8.3 days after surgery. CONCLUSION: The
      implantation of colorectal stents before elective surgery constitutes a good
      alternative to surgery in the acute lower intestinal occlusion (left colon and
      rectum-sigmoid emergency).

PMID- 8983306
TI  - [Ectopic pancreas].
AB  - We describe ten cases of ectopic pancreas operated on in the Hospital General
      Universitario, Alicante, between 1970 and 1994. Average age of patients was 47.7
      (range 3-75); five men and five women. In four cases there was associated
      digestive tract bleeding, three had chronic gastroduodenal ulcers, two
      pancreaticobiliary disease, and one suprarenal abnormalities. In four cases the
      ectopic gland was found in the gastric antrum; in four cases in the duodenum and
      in the remaining two cases in the first jejunal loop. Average diameter was 2.3 cm
      (range 0.6-6). In six cases complete pancreas tissue was found, in three an
      exocrine pancreas and in one a purely endocrine pancreas. In two patients the
      presence of the choristoma and the clinical findings due to erosion of the
      subjacent mucosa may be related. In one case the finding of cholelithiasis,
      intradiverticular papilla, and periampullar ectopia together with clinical
      features of recurrent pancreatitis may also be linked. In the remaining seven
      cases no relationship was found between the ectopic pancreas and the clinical
      features. Our series suggest that simple resection is best to avoid
      complications.

PMID- 8983307
TI  - [Diseases of the digestive system and a system for patient classification:
      diagnostic-related groups (DRG)].
AB  - In the last years different classification systems for hospitalized patients have
      been developed in the United States, that allow to evaluate different aspects of
      any Hospital: The quality, the efficacy and the efficiency. The classification of
      "The Diagnosis Related Groups" (DRG) relates the hospitalized patients with the
      expenses that they generate, and it is the most used in Europe. In the version
      DRG-All Patient, all the diagnoses and procedures of the hospitalized patients,
      using the International Classification of Diseases, are divided in to 25 Major
      Diagnostic Categories (MDC) where each one excludes all the others. We describe
      the behavior with respect to the age, sex and stay of all the GDR integrated in
      the CDM 6 and 7: diseases and disorders of the digestive tract, and diseases and
      disorders of the hepatobiliary system and the pancreas. The study has been
      carried out with a national data base of two millions of cases seen from 214
      acute-care Hospitals. The MDC number 6 is the most frequent, with an important
      number of patients in the pediatric age; it is more frequent in males; the
      average stay is 8.59 days and 19 GDR (36.5%) have a variation coefficient greater
      than one. The other MDC, number 7 is less frequent, the majority of the patients
      are between 60-80 years of age, the average stay is 12.2 days with a coefficient
      of variation greater than one in 4 GDR (17.4%). Clinical Services should know the
      characteristics and behavior of their patients, as well as the comparison with
      the national data bases. This may allow a control of the quality and the costs by
      using a common "language" with the managers.

PMID- 8983308
TI  - [Treatment of hepatocarcinoma].

PMID- 8983309
TI  - [Survey on Helicobacter pylori and peptic ulcer in Spain].
AB  - OBJECTIVE: The goal of this study is to determine, through a national survey, the
      degree of acceptance among gastroenterologists of the relationship between
      Helicobacter pylori and peptic ulcer, and how they manage their patients
      according to this association. STUDY DESIGN: An observational study through a
      self-administered questionnaire. PARTICIPANTS: The questionnaire was distributed
      to 690 gastroenterologists from all over Spain. The questionnaire was answered by
      687 specialists. RESULTS: Most (98.1%) Spanish specialists accept the
      relationship, 1.5% are reluctant, and 0.3% are irresolute. Eradication treatments
      are prescribed by 96.4% of the gastroenterologists, mainly
      omeprazole+amoxicillin, in 1994, though only 40.8% of gastroenterologists always
      prescribe it for H. pylori positive peptic ulcer. A control of the effectiveness
      of the treatment is undertaken by 84.3% of gastroenterologists. CONCLUSIONS: The
      relationship between H. pylori and ulcer is accepted by Spanish
      gastroenterologists, as well as eradication therapy.

PMID- 8983310
TI  - [Eosinophilic esophagitis: an underdiagnosed entity?].
AB  - Eosinophilic esophagitis is an exceptional entity, although the number of
      published cases has increased three times during the last 3 years. We report the
      case of an 18-year-old male with a long esophageal stenosis due to eosinophilic
      esophagitis. Clinical, radiologic, endoscopic and manometric outcome was
      satisfactory after prednisone therapy. Although isolated esophageal involvement
      may occur, disseminated eosinophilic esophago-gastro-intestinal disease is more
      frequent. The disease is usually diagnosed in young male patients, presenting
      with dysphagia and, to a lesser extent, chest pain. Previous allergic conditions
      are reported in 80% of cases and peripheral eosinophilia is present in 80% of
      patients. Esophageal stenosis is present in 72% of cases and manometric
      alterations are found in 47% of patients. Radiographic findings are nonspecific
      and include stenosis and rigidity. Endoscopic features are not specific either,
      but diagnosis may be achieved by endoscopic biopsy. Corticosteroids and sodium
      chromoglycate have proved to be useful, with good therapeutic response being
      reported in 90% of patients with this underestimated disease.

PMID- 8983312
TI  - [Intense icterus in the course of EBV infectious mononucleosis].
AB  - Infectious mononucleosis induced by the Epstein Barr Virus (EBV) is a benign
      illness that is frequently accompanied by a slight hepatic disfunction. On
      occasion it may be accompanied by autoimmune hemolytic anemia of little clinical
      importance. Nevertheless, this association can cause a serious set of symptoms
      that can put the patient's life in danger if it is not treated quickly. We
      present the case of a 21-year-old male with infectious mononucleosis and severe
      jaundice (total bilirubin 40 mg/dl) due to the combination of diseased liver and
      secondary autoimmune hemolytic anemia, caused by the EBV infection.

PMID- 8983311
TI  - [Primary melanoma of the esophagus. 2 new cases].
AB  - Primary melanoma of the esophagus is rare. Until 1990, eight cases had been
      reported in Spain. We report two patients, 50 and 61-year-old men. Melanomas were
      located in the distal esophagus and were polypoid (5-6 cm), pediculated and
      pigmented. Endoscopic biopsy was diagnostic in both cases. Fontana staining
      technique and monoclonal HMB-45 and S-100 antibodies were used. A revision of
      clinical characteristics, treatment and survival of the patients with primary
      melanoma of the esophagus in our country is made.

PMID- 8983313
TI  - [Symptomatic treatment of a tracheogastric neoplastic fistula with an
      intragastric autoexpandable prosthesis].

PMID- 8983314
TI  - [Urticariform reaction: endoscopic diagnosis].

PMID- 8983315
TI  - Calcium antagonists: never let the truth get in the way of a good story.

PMID- 8983316
TI  - Comparative efficacy and tolerability of two diclofenac formulations in the
      treatment of painful osteoarthritis.
AB  - The efficacy and tolerability of a new resinate formulation of diclofenac 75mg
      taken once or twice daily were compared with that of conventional enteric-coated
      diclofenac sodium 50mg tablets given two or three times daily in a double-blind,
      randomised, between-patient, 12-week trial in 216 adult patients suffering from
      painful osteoarthritis of the hip and/or knee. Similar and clinically significant
      reductions in the mean intensity scores of pain at rest or on activity were
      observed after treatment with either formulation. Global evaluations showed the
      overall response rate to range between 60% and 75%. A significant analgesic
      effect was obtained within two weeks of treatment with 150mg diclofenac daily;
      this improvement was maintained on reduction of the dosage to 75-100mg over the
      next ten weeks. One or more drug-related adverse events, predominantly
      gastrointestinal adverse events, were reported by 40% and 38% of patients in the
      diclofenac resinate and diclofenac sodium groups, respectively.

PMID- 8983317
TI  - Clinical challenge--an experience of spontaneous transmural rupture of the
      oesophagus in Taiwan.
AB  - In Taiwan, spontaneous oesophageal rupture is uncommon but the outcome is often
      lethal because of failure to make an early diagnosis. We have analysed clinical
      data, management and the risk factors that affect mortality for a consecutive
      series of 11 patients who had spontaneous oesophageal perforation between 1983
      and 1994. The primary symptom was chest or abdominal pain, which was present in
      100% of patients; 91% of patients had abnormal chest x-ray (63% pleural effusion,
      46% pneumomediastinum, 37% subcutaneous emphysema). In our series of patients the
      lower thoracic area was the most common location of the perforation (80% of
      patients. There were no statistically significant differences in mortality due to
      age, underlying disease, perforation size, location or surgical methods. A poor
      prognosis seems to be correlated with the time elapsed between the perforation
      and treatment (especially if > 72 hours) (p < 0.05), respiratory failure (p <
      0.05), and heavy contamination of the mediastinum (p < 0.05). The clinical
      findings depend on the location and time of perforation. History, chest x-ray and
      oesophagogram are the most useful diagnostic tools. Early diagnosis and treatment
      are mandatory for these patients.

PMID- 8983318
TI  - Efficacy of ramipril versus enalapril in patients with mild to moderate essential
      hypertension.
AB  - This double-blind, randomised, cross-over study investigated the antihypertensive
      efficacy of ramipril and enalapril was completed by 30 patients with mild-to
      moderate essential hypertension. After a four-week placebo run-in phase, the
      patients received either 2.5mg ramipril or 10mg enalapril once daily for four
      weeks. The dosages were increased to 5mg ramipril and 20mg enalapril for a
      further four weeks. After a placebo washout phase of four weeks, the patients
      were crossed over to the alternative treatment. The decrease in average 24-hour
      ambulatory diastolic blood pressure from week 0 to week 8 was 1.6mmHg greater
      with ramipril than enalapril (90% confidence interval 0.6-2.7mmHg). The
      corresponding reduction in for systolic blood pressure was also greater with
      ramipril than enalapril by 2.4mmHg (90% confidence interval: 0.5-4.2mmHg). For
      the difference in the drop of 24-hour ambulatory diastolic blood pressure between
      ramipril and enalapril the lower level of the 90% confidence interval (CI) is
      above the clinically relevant difference of -3mmHg. This is an indication that
      ramipril (2.5 and 5mg dose) is at least as effective as enalapril (10 and 20mg
      dose) in decreasing blood pressure in patients with mild-to-moderate essential
      hypertension. The duration of adequate antihypertensive effect was relatively
      long for both ramipril and enalapril; however, ramipril tended to have a more
      prolonged antihypertensive effect. Ramipril had a higher diastolic and systolic
      trough/peak ratio than enalapril, resulting in a more uniform antihypertensive
      effect over the 24-hour treatment period. Both ramipril and enalapril were well
      tolerated and the two treatment groups had similar safety profiles.

PMID- 8983319
TI  - Methotrexate in the treatment of children with chronic arthritis--long-term
      observations of efficacy and safety.
AB  - In a study to investigate the efficacy and toxicity of long-term methotrexate
      (MTX) therapy in children with chronic arthritis, the medical records of 26
      children (seven boys and 19 girls) with juvenile rheumatoid arthritis (JRA) were
      reviewed retrospectively. The patients received MTX therapy for a mean of three
      years (range, six months to six years). A clinically significant response
      occurred in 19 children (73.1%): remission in ten (38.5%) and improvement (25%
      reduction in the number of actively inflamed joints) in nine (34.6%). Concomitant
      prednisolone therapy was reduced in 13 out of 14 children (93%). Haemoglobin
      levels and erythrocyte sedimentation rates were statistically significantly
      improved over baseline after MTX therapy. Six (23%) children experienced toxic
      effects during MTX therapy. One patient discontinued the MTX treatment after 18
      months because of jaundice and raised liver enzymes. It is concluded that the
      study confirms the efficacy, and acceptable toxicity profile, of MTX given over a
      period of several years to children with JRA.

PMID- 8983320
TI  - Advances in the treatment of schizophrenia.
AB  - We review advances in the treatment of schizophrenia. We begin with an overview
      of antipsychotic drug development, focusing on the in vitro and in vivo binding
      profiles of clozapine and a new generation of D2:5HT antagonists. We then
      consider the main barriers to effective treatment: non-compliance (and side
      effects) of medication, recurrent relapse, 'treatment resistance', negative
      symptoms and neurocognitive deficits. Within this framework, we review the
      mechanisms of action and clinical uses of the 'atypical' antipsychotic drugs. We
      also show how a variety of psychosocial interventions, particularly those that
      incorporate cognitive techniques, can be used in combination with pharmacotherapy
      to overcome the same clinical hurdles.

PMID- 8983321
TI  - Management of chronic non-malignant pain.
AB  - Chronic non-malignant pain is often treated inadequately because of opiophobia.
      There is no scientific justification for this fear. With close monitoring and
      frequent controls, opioids are safe for this kind of pain. There is no scientific
      evidence that patients with chronic non-malignant pain are more prone to
      addiction or tolerance. It is also pertinent to consider that the endpoint of
      chronic pain treatment is not just freedom from pain but global wellbeing.

PMID- 8983322
TI  - Bacterial vaginosis.
AB  - Bacterial vaginosis (BV) is an alteration of the vaginal flora, where the
      normally predominant lactobacilli are replaced by a cocktail of organisms
      including Gardnerella vaginalis and anaerobes. It presents with a grey,
      homogenous, offensive vaginal discharge that has a raised pH. However, around
      half the women with this condition are asymptomatic. Diagnosis is best made by
      microscopic examination of a Gram-stained smear of vaginal secretions. Treatment
      is with metronidazole or clindamycin. The indications for treatment of
      asymptomatic BV are not clear, but women should probably be treated before any
      invasive gynaecological procedure, including intrauterine contraceptive device
      (IUCD) insertion. BV during pregnancy is associated with preterm labour, although
      a causal effect is not proven; studies are in progress to determine whether
      treatment of BV will improve the outcome of these pregnancies.

PMID- 8983323
TI  - Surgery for asymptomatic carotid artery stenosis.
AB  - The recent European Carotid Surgery Trial (ECST) and North American Symptomatic
      Carotid Endarterectomy Trial (NASCET) have clearly defined a population who
      benefit from carotid artery endarterectomy (CAE). However these trials used
      different criteria to identify > 70% stenosis of the internal carotid artery
      (ICA). The role of CAE in asymptomatic ICA stenosis has been investigated by the
      Carotid Artery Stenosis with Asymptomatic Narrowing Operation Versus Aspirin
      (CASANOVA) study, the Veterans Administration Asymptomatic Carotid Study (VAACS)
      and the Asymptomatic Carotid Artery Stenosis (ACAS) trials, all of which have
      design limitations. The Asymptomatic Carotid Stenosis Trial (ACST) is still
      recruiting patients but until the natural history of asymptomatic ICA disease is
      understood, the role of surgical intervention will continue to be controversial.

PMID- 8983324
TI  - Frontal lobe tumours.
AB  - The diagnosis of frontal lobe tumours can easily be missed. Subtle mood or
      personality changes may be evident only after questioning of close family,
      friends or carers. Neurological signs may be absent.

PMID- 8983325
TI  - Osteoporosis care--the need for a district-wide approach.
AB  - Osteoporosis has now been recognised by both the World Health Organization and
      the UK Department of Health as a major public health problem. It causes more than
      200,000 fractures each year in the UK--at an estimated cost to the NHS of 750
      million pounds. For the individual, it presents a burden of pain, deformity and
      premature death.

PMID- 8983327
TI  - An atypical case of atypical pneumonia.
AB  - A 23-year-old man, previously fit and well, presented with an atypical pneumonia,
      associated with microangiopathic anaemia, thrombocytopenia, rhabdomyolysis and
      renal impairment. Despite administration of intravenous fluids and antibiotics,
      his condition rapidly deteriorated, and the possibility of an aggressive
      connective tissue disorder was raised. Thus he was treated with high-dose oral
      steroids and plasma exchange until autoantibodies were shown to be negative. At
      this stage it transpired that the patient had swallowed water from a stream three
      weeks earlier, and leptospira antibody titres were subsequently found to be
      elevated. Antibiotics were continued, and after a protracted course he made a
      full recovery. Leptospirosis should be remembered as a rare cause of atypical
      pneumonia, particularly if there is associated hepatic or renal impairment.

PMID- 8983326
TI  - Autoimmune polyglandular syndrome and primary biliary cirrhosis.
AB  - Liver involvement in autoimmune polyglandular syndrome (APS) in the form of
      chronic active hepatitis has been well described. However, to our knowledge,
      primary biliary cirrhosis in APS has not been reported. Here we report the case
      of a 27-year-old man who presented with classical insulin-dependent diabetes
      mellitus and subsequently developed Hashimoto's thyroiditis, hypogonadism, and
      primary biliary cirrhosis. The latter diagnosis was confirmed by a cholestatic
      pattern of liver enzymes, positive anti-mitochondrial antibody, normal
      cholangiogram, and characteristic liver biopsy findings. Primary biliary
      cirrhosis should probably be regarded as a possible, though uncommon, component
      of APS.

PMID- 8983328
TI  - Focal lymphoid hyperplasia of the terminal ileum mimicking Crohn's disease.
AB  - Focal lymphoid hyperplasia of the terminal ileum is a rare cause of terminal
      ileitis. We describe the case of a 13-year-old boy with a stricture of the
      terminal ileum that was diagnosed as Crohn's disease on barium meal and follow
      through. This failed to resolve on steroid therapy and the boy eventually
      required resection of his terminal ileum. Pathology of the terminal ileum showed
      focal lymphoid hyperplasia and not Crohn's disease.

PMID- 8983329
TI  - Acute psychosis associated with abrupt withdrawal of carbamazepine following
      intoxication.
AB  - Carbamazepine is regularly used in the treatment of trigeminal neuralgia.
      Although exacerbation of psychosis has been described following abrupt
      discontinuation of carbamazepine in chronic schizophrenics, a withdrawal syndrome
      has not been reported previously in patients treated for trigeminal neuralgia.
      The case presented here suggests that abrupt withdrawal of toxic concentrations
      of carbamazepine may precipitate a withdrawal reaction, which is manifest some
      days after discontinuation of the drug. Therefore it may be advisable to withdraw
      therapy slowly in these situations.

PMID- 8983331
TI  - 1996 Annual meeting of the American Society of Regional Anesthesia. San Diego,
      California, March 28-31, 1996. Abstracts.

PMID- 8983330
TI  - Pityriasis rubra pilaris and human immunodeficiency virus infection--type 6
      pityriasis rubra pilaris?

PMID- 8983332
TI  - Polyamines induce blood-brain barrier disruption and edema formation in the rat.
AB  - Polyamines (PA) are derived from ornithine by the enzyme ornithine decarboxylase
      (ODC), which is activated very rapidly as acute and delayed responses to brain
      ischemia and trauma. Polyamines play a role in the disruption of the blood-brain
      barrier (BBB) in different pathological states. This study examined the effect of
      exogenous polyamines, administered intracerebrally (i.c.v.) or intracarotidly on
      BBB function. Putrescine, spermidine and spermine, given individually, were found
      to disrupt BBB integrity within 15 min of i.c.v. administration (p = 0.03; p =
      0.0013; p = 0.042 vs saline treated rats, respectively). The effect was still
      evident after 1 h; however, since the saline treated rats also showed increased
      permeability of Evans blue at this time, there was no statistical difference
      between polyamines or saline treated rats 1 h post injection. When injected into
      the carotid artery, rapid increase in BBB permeability was found 1 min after
      putrescine and spermidine (p < 0.01 vs saline), with a slight decline at 15 min.
      A slower effect was noticed after spermine administration which reached
      significance only at 15 min. These results suggest a role for PA as mediators of
      vasogenic edema formation in the brain soon after brain injuries which induce
      increased production of these compounds.

PMID- 8983333
TI  - Susceptibility of the injured rat brain to CNS oxygen toxicity.
AB  - The possibility of an altered susceptibility of the injured brain to central
      nervous system (CNS) oxygen toxicity was examined in awake rats. Moderate to
      severe closed head injury with diffuse axonal damage was produced in anesthetized
      rats by the fluid percussion method (2-2.5 atm), after which chronic EEG
      electrodes were implanted. Twenty-four hours later, the rats were exposed to 5
      atm abs (506.5 kPa) oxygen and the time to appearance of paroxysmal EEG patterns
      was noted. The difference between the 19 minute median latency of this group and
      16 minute of a control group which underwent a sham operation did not reach
      statistical significance. Some injured animals convulsed with minimal or no EEG
      changes. The clinical implication could be that brain injured patients are not at
      higher risk of CNS oxygen toxicity but the EEG alterations that could potentially
      be used to forecast incipient convulsions, or be the indication of actual
      convulsions in the intact brain of a paralyzed patient, may not always be
      present.

PMID- 8983334
TI  - Continuous multiparametric monitoring of brain activities following fluid
      percussion injury in rats: preliminary results.
AB  - Severe head injury can result in a high mortality rate or irreversible brain
      damage. One technique used to induce traumatic brain injury (TBI) is exposure of
      the brain to fluid percussion pressure while monitoring the increase in
      intracranial pressure (ICP). Since brain injury is a multifactorial,
      pathological, time-dependent state, the multiparametric monitoring approach was
      adopted for studying fluid percussion effects on the rat brain. A multiprobe
      assembly (MPA) connected to the brain in vivo (right hemisphere) enabled the
      simultaneous monitoring of CBF, NADH redox state, extracellular K+, Ca2+, H+
      levels as well as DC potential, ECoG and ICP. The animal was connected to the
      monitoring system and exposed to TBI after a recuperation period of at least 3
      hours after the end of the operation. Two typical responses to TBI were recorded
      in our preliminary experiments. When severe injury was induced, ischemic
      depolarization (ID) developed, whereas mild or moderate injury led to repetitive
      spreading depression (SD) cycles. The relationship between the ID and SD observed
      under TBI is important to the understanding of the mechanism of brain injury. ICP
      before injury was between 2-6 mm Hg and increased to 20-22 mm Hg 2-3 minutes
      after the ID. After severe head injury, ICP remained high and in some cases
      increased to critical values causing death of these animals. Some animals
      developed seizures at various stages after the TBI. Hyperbaric oxygenation was
      used as a therapeutic tool to treat severely injured animals. These preliminary
      results suggest that it is feasible and practical to use the MPA approach for
      monitoring the brain after TBI.

PMID- 8983335
TI  - The influence of cortisol on spontaneous and 5HT stimulated prolactin release in
      man.
AB  - The role of cortisol in influencing spontaneous and 5HT mediated prolactin
      release was investigated in 17 healthy male subjects who took part in 3 separate
      studies. Five of the subjects were treated for 24 h with metyrapone (the 11 beta
      hydroxylase inhibitor which prevents the conversion of 11-deoxycortisol to
      cortisol) on one occasion and placebo for 24 h on another. On both test occasions
      their spontaneous prolactin was monitored before they underwent serotonergic
      stimulated prolactin release using D-fenfluramine (30 mg). Treatment with
      metyrapone enhanced the spontaneous nocturnal prolactin surge and also the
      prolactin response to D-fenfluramine. Six of the subjects were treated for 24 h
      with hydrocortisone on one occasion or placebo on the other. With hydrocortisone
      treatment no nocturnal increase in prolactin was observed and the response to D
      fenfluramine challenge was attenuated. To determine whether the influence of
      cortisol on prolactin release is at a pituitary or supra-pituitary site 6
      subjects were tested with thyrotropin releasing hormone (TRH) which acts directly
      on the pituitary to bring about prolactin release. They were each tested twice,
      following either metyrapone or placebo treatment. The rise following metyrapone
      was significantly greater than that seen following placebo. The results suggest
      that cortisol influences both spontaneous and 5HT stimulated PRL release,
      probably acting at a pituitary level.

PMID- 8983336
TI  - Nitric oxide: a mediator in anaphylactic shock in guinea-pigs.
AB  - In this study we show that the pathophysiology of anaphylaxis includes generation
      of nitric oxide (NO), a very powerful, short-acting vasodilator. Guinea-pigs
      sensitized to ovalbumin were treated with 200 microgram/kg diphenylene iodonium
      (DPI), and NO synthase inhibitor, prior to antigen challenge. Mortality following
      the challenge fell from 71 to 39% (p < 0.001, n = 59). In the Langendorff
      preparation perfused isolated hearts from sensitized guinea-pigs were challenged
      to initiate cardiac anaphylaxis. The coronary flow rate (CFR), a direct
      reflection of coronary arterial resistance, was reduced by antigen challenge to
      56 +/- 4% (n = 16) of the basal rate. DPI (2 micrograms/ml) intensified the
      antigen-induced fall in CFR to 13 +/- 3% of control (p < 0.005, n = 5), and the
      false substrate for NO, L-N-methylarginine, to 37 +/- 3% (p < 0.05, n = 4).
      Sodium nitroprusside (SNP), a NO generator, raised the basal CFR by 46% (from
      11.2 +/- 1.7 ml/min to 16.3 +/- 1.9 ml/min) and blunted the antigen-induced fall
      in CFR. Paradoxically, DPI, which can inhibit flavoprotein enzymes other than NO
      synthase, potentiated the vasodilator effect of SNP, raising the basal CFR by
      116%. Together these results strongly indicate that the vasodilator NO is
      generated in anaphylaxis. However, whereas in the heart it may function as a
      counterweight to the vasospasm of the coronary arteries, in the intact animal it
      appears to be a major contributor to the potentially lethal hypotension of
      anaphylactic shock.

PMID- 8983337
TI  - Irradiation induced blood flow changes in the breast during radiotherapy--a pilot
      study.
AB  - Skin blood flow and underskin temperature were measured in breasts during the
      complementary radiotherapy following lumpectomy, using the noninvasive transient
      thermal clearance method. On average, blood flow and tissue temperature increased
      at the start of the irradiation then slightly decreased. The response varied
      significantly among the patients. The increase in blood flow is associated with
      the vasodilatation which accompanies irradiation-induced inflammation and the
      method enables the assessment of this vasodilatation during the irradiation
      treatment. The decrease of blood flow after the initial increase is attributed to
      vascular damage. The method provides a noninvasive means for the evaluation of
      radiation effects on individual patients during radiotherapy.

PMID- 8983338
TI  - Vehicles, chelators, and radionuclides: choosing the "building blocks" of an
      effective therapeutic radioimmunoconjugate.

PMID- 8983339
TI  - Synthesis of short polyoxyethylene-based heterobifunctional cross-linking
      reagents. Application to the coupling of peptides to liposomes.
AB  - We describe the synthesis of [2-[2-[2-[(2-bromoacetyl)amino]ethoxy]ethoxy]ethoxy
      acetic acid (7), [2-[2-(2,5-dioxo-2,5-dihydropyrrol-1-yl)ethoxy]ethoxy] acetic
      acid (11), and [2-[2-(pyridin-2-yldisulfanyl)-ethoxy]ethoxy] acetic acid (16),
      three new thiol-reactive heterobifunctional reagents, and the preparation of
      their corresponding dipalmitoylphosphatidylethanolamine derivatives (8, 12, and
      17). Such phospholipid amide derivatives were aimed to be incorporated into the
      bilayers of liposomal constructs used for immunization with e.g. synthetic
      peptides. The spacer arms introduced by 8, 12, and 17 are hydrophilic
      polyoxyethylene chains of variable lengths that were expected to provide a good
      accessibility to their conjugates and have a lesser intrinsic immunogenicity than
      the spacer introduced by N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine
      (MPB-PE), a classical reagent used for conjugation of ligands to the surface of
      liposomes. Such an immunogenicity might be prejudicial (e.g. carrier-induced
      epitopic suppression) to the development of synthetic vaccination formulations.
      Moreover, the derivatives 8, 12, and 17 allowed the coupling of peptides, bearing
      a thiol function, to their liposomal carrier via two types of linkages, i.e.
      stable thio ether (8 and 12) and bioreducible disulfide (17) bonds; this might be
      of importance in the mechanism of antigen presentation by competent cells. Using
      CG-IRGERA as a model peptide, the rate of coupling to 8, 12, and 17 was assessed
      as a function of pH.

PMID- 8983341
TI  - Labeling cyclic glycoprotein IIb/IIIa receptor antagonists with 99mTc by the
      preformed chelate approach: effects of chelators on properties of [99mTc]chelator
      peptide conjugates.
AB  - Several cyclic GPIIb/IIIa receptor antagonists were labeled with 99mTc by the
      preformed chelate approach using chelators such as H4L1 [4,5
      bis(mercaptoacetamido)pentanoic acid], H4L2 [3,4-bis-(mercaptoacetamido)benzoic
      acid], H3L3 [2-(mercapto)ethylaminoacetyl-L-cysteine], H4L4 [N
      (mercaptoacetyl)glycylglycylglycine], H4L5 [N-[2
      (mercapto)propionyl]glycylglycylglycine], and H4L6 [N-[2
      (mercapto)propionyl]glycylglycyl-gamma-aminobutyric acid]. In this approach, the
      [99mTc]chelator complexes are formed first, followed by the activation of the
      carboxylic group on the complex by formation of its tetrafluorophenol (TFP) ester
      and the conjugation of the TFP ester with an amino group of a cyclic GPIIb/IIIa
      receptor antagonist. The 99mTc-labeled cyclic GPIIb/IIIa receptor antagonists
      were characterized by radio-HPLC (high-performance liquid chromatography);
      differences in lipophilicity of the [99mTc]chelator-peptide conjugate are
      attributable to the effects of both the cyclic peptide and the chelator.

PMID- 8983340
TI  - Enzyme-linked immunosorbent assay detection of pyrrolizidine alkaloids:
      immunogens based on quaternary pyrrolizidinium salts.
AB  - Polyclonal antibody-based enzyme-linked immunosorbent assays (ELISAs) were
      developed for the detection of retrorsine (1, 351 g/mol), monocrotaline (2, 325
      g/mol), and retronecine (3, 155 g/mol) in the parts per billion (ppb) range. A
      set of three bifunctional linking arms (6-8) was synthesized. By N-alkylation of
      pyrrolizidine alkaloids (PAs) retrorsine, monocrotaline, and retronecine
      acetonide (9), six haptens (6.1, 6.2, 7.1, 7.2, 7.9, and 8.9) were synthesized
      and used to generate rabbit antisera. The resulting anti-retrorsine antiserum
      gave a 50% inhibition (I50) value of 0.9 +/- 0.2 ppb for retrorsine with
      detection limits of 0.5-10 ppb. The same ELISA system also detected isatidine (4,
      retrorsine N-oxide) dihydrate (403 g/mol) with an I50 of 1 ppb and senecionine
      (5,352 g/mol) with an I50 of 100 ppb. A second monocrotaline-based ELISA detected
      monocrotaline with an I50 of 36 +/- 9 ppb 2 with detection limits of 5-500 ppb
      and shows no cross-reactivity with 1 or 5; this ELISA demonstrates the potential
      for the substrate-specific detection method. A third retronecine-based ELISA
      detects 3 with an I50 of 3000 +/- 600 ppb (3 +/- 0.6 ppm) and detection limits of
      600-10,000 ppb. None of these ELISAs cross-react with the structurally similar
      swainsonine (10) or lupinine (11) alkaloids. PAs were detected in extracts of
      Senecio vulgaris and Crotalaria retusa, but not in Lupinus spp., as a
      demonstration of the ELISA's usefulness.

PMID- 8983342
TI  - Biological evaluation of 99mTc-labeled cyclic glycoprotein IIb/IIIa receptor
      antagonists in the canine arteriovenous shunt and deep vein thrombosis models:
      effects of chelators on biological properties of [99mTc]chelator-peptide
      conjugates.
AB  - A series of 99mTc-labeled cyclic glycoprotein IIb/IIIa receptor antagonists,
      [99mTcO(L1-III)]-, [99mTcO-(L6-III)]-, [99mTcO(L1-V)]-, and [99mTcO(L6-V)]-, were
      evaluated in a canine arteriovenous (AV) shunt model for their potential use as
      thrombus imaging agents. The thrombus formed consists of a platelet-rich head and
      a fibrin-rich tail. All four agents were incorporated into the growing thrombus
      under both arterial (platelet-rich) and venous (platelet-poor) conditions. The
      rank order for uptake was [99mTcO(L1-V)]- > [99mTcO(L6-V)]- > [99mTcO(L6-III)]- >
      [99mTcO(L1-III)]- (arterial range, 5.8-0.47% id/g; venous range, 0.58-0.04%
      id/g). The uptakes of both [99mTcO(L6-III)]- and [99mTcO-(L1-III)]- under both
      arterial and venous conditions were not significantly greater than that of
      [99mTc]-albumin and [125I]fibrinogen. In contrast, the uptakes of both [99mTcO(L1
      V)]- and [99mTcO(L6-V)]- were significantly greater than those of [99mTc]albumin
      and [125I]fibrinogen and comparable to that of [111In]platelets under both
      arterial and venous conditions. All four [99mTc]chelator-peptide conjugates are
      cleared faster than the controls with the clearance of the conjugates of peptide
      III faster than that of the conjugates of peptide V. The differences in
      incorporation are attributable to the effect of both the cyclic peptide and the
      chelator. The conjugate [99mTcO(L1-V)]- was also studied using a canine DVT (deep
      vein thrombosis) model. [99mTcO(L1-V)]- was actively incorporated into the
      growing thrombus with images clearly detectable within 15 min postinjection. At 2
      h postinjection, thrombus/blood and thrombus/muscle ratios [region of interest
      (ROI)/background] were approximately 7/1 and 10/1, respectively. This clearly
      demonstrated that the conjugate [99mTcO(L1-V)]- has the potential for rapid
      diagnosis of thrombolic events occurring under both arterial and venous
      conditions.

PMID- 8983343
TI  - Hypersensitization of multidrug resistant human ovarian carcinoma cells by
      pluronic P85 block copolymer.
AB  - The chemosensitizing effect of Pluronic P85 block copolymer were studied using
      two human ovarian carcinoma sublines: the glycoprotein P (P-gp) multidrug
      resistant (MDR) SKVLB cells and non-MDR SKOV3 cells. The dramatic increase (up to
      700 times) in the daunorubicin cytotoxic activity was observed in the presence of
      0.01% (22 microM) to 1% (2.2 mM) copolymer in the case of SKVLB cells. By
      contrast, the copolymer induced a less than 3-fold increase in the drug activity
      in SKOV3 cells. As a result, the MDR subline demonstrated much higher response
      ("hypersensitivity") to the daunorubicin/ Pluronic compared to that of the non
      MDR cells. The copolymer increased the cytotoxic effects of other MDR type drugs
      (doxorubicin, epirubicin, vinblastine, and mitomycin C) by a factor of 20-1000
      and non-MDR type drugs (methotrexate and cisplatin) by a factor of 2-5.5. The
      daunorubicin influx in the cytoplasm and nuclei of SKVLB cells was also increased
      in the presence of the copolymer, while in SKOV3 cells, it remained practically
      unchanged. However, the hypersensitization of the MDR cells by the copolymer
      could not be merely explained by the P-gp modulation. Therefore, the possible
      role of the copolymer in inhibition of non-P-gp drug resistance is hypothesized,
      which may also explain the sensitization of MDR cells with respect to non-MDR
      type drugs as well as sensitization of parental cells. The concentration
      dependence of the IC50 in MDR cells indicates that just the copolymer unimers are
      responsible for the hypersensitization effect. The results obtained suggest that
      Pluronic P85 can be used as a delivery system to enhance the activity of
      antineoplastic agents against MDR tumors.

PMID- 8983344
TI  - Synthesis of cobalamin-biotin conjugates that vary in the position of cobalamin
      coupling. Evaluation of cobalamin derivative binding to transcobalamin II.
AB  - Six cobalamin-biotin conjugates have been prepared. The cobalamin-biotin
      conjugates were prepared to evaluate the effect that the location of attachment
      had on the binding with transcobalamin II (TCII), the cobalamin binding protein
      in plasma, and to evaluate their potential use for in vitro and in vivo
      applications. This study focused only on the effect of binding with TCII. To
      decrease the possibility of steric problems in binding of the cobalamin
      conjugates with TCII, and biotin's binding with streptavidin or avidin, moieties
      of 11-18 atoms in length were used as linkers. Four biotin conjugates were
      prepared which were attached to the corrin ring of the cobalamin molecule (on b-,
      c-, d-, and e-side chains). One conjugate was attached to the 5'-OH of the ribose
      moiety, and another conjugate was attached at the cobalt metal (in place of the
      cyanide moiety of cyanocobalamin). Competitive binding studies were conducted
      where various amounts of the cobalamin-biotin conjugates and their precursor
      cobalamin derivatives competed with [57Co]cyanocobalamin for binding of
      recombinant human TCII (rhTCII). Evaluation of cobalamin derivatives which were
      conjugated at the 5'-OH of ribose or the cobalt metal center indicated that
      conjugation at either of these positions had little effect on binding with
      rhTCII. However, conjugates where the attachment was made on the corrin ring
      substituents had a large variation in binding with rhTCII. Conjugates on the e
      propionamide side chain had little effect (relative affinity was equal to or
      decreased less than a factor of 3) on binding with rhTCII, conjugates of the b
      isomer had decreased binding (relative affinity decreased less than a factor of
      10), conjugates of the d-propionamide had further decreased binding (relative
      affinity decreased between 44 and 69 times), and conjugates on the c-acetamide
      group had poor binding to rhTCII (relative affinity decreased between 295 and
      1160 times). The significance of the side chains on the corrin ring in providing
      specificity and high-affinity binding with rhTCII is discussed.

PMID- 8983345
TI  - Enhanced binding and inertness to dehalogenation of alpha-melanotropic peptides
      labeled using N-succinimidyl 3-iodobenzoate.
AB  - Two peptides of potential utility for targeting melanoma cells, alpha-melanocyte
      stimulating hormone (alpha-MSH) and its more potent analogue [Nle4,D-Phe7]-alpha
      MSH, were radioiodinated in 45-65% yield using N-succinimidyl 3
      [125I]iodobenzoate (SIB). To determine whether this labeling method resulted in
      improved in vitro and in vivo characteristics, these peptides also were labeled
      with 131I by direct iodination with the iodogen method. For alpha-MSH, the rapid
      tissue clearance of both radionuclides in mice was consistent with rapid
      degradation of the peptide; however, significantly lower levels of 125I were
      observed in thyroid and stomach, reflecting a greater inertness to deiodination.
      More extensive comparisons were performed with [Nle4,D-Phe7]-alpha-MSH. The in
      vitro binding of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH (prepared using SIB) to
      the murine B-16 melanoma cell line, 34.1 +/- 4.7%, was more than twice as high as
      that for [Tyr2(131I),Nle4,D-Phe7]-alpha-MSH (15.0 +/- 0.1%), and its KD was more
      than 10-fold lower than that for conventionally labeled peptide (10 +/- 5 versus
      140 +/- 14 pM). The normal tissue clearance of [Nle4,D-Phe7,Lys11-(125I)IBA]
      alpha-MSH in mice was faster than that of [Tyr2(131I),-Nle4,D-Phe7]-alpha-MSH.
      The 19-40-fold lower activity concentrations of [Nle4,D-Phe7,Lys11-(125I)IBA]
      alpha-MSH in tissues accumulating free iodide (thyroid and stomach) suggest a
      greater inertness of this peptide to deiodination. The primary urinary catabolite
      of [Nle4,D-Phe7, Lys11-(125I)IBA]-alpha-MSH was the lysine conjugate of
      iodobenzoic acid, whereas radioiodide was the chief catabolite generated from
      [Tyr2(131I),Nle4,D-Phe7]-alpha-MSH. We conclude that further evaluation of
      [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH for targeting alpha-MSH receptors is
      warranted and that SIB may be a useful method for the radioiodination of
      peptides.

PMID- 8983346
TI  - Novel non-nucleosidic building blocks for the preparation of multilabeled
      oligonucleotides.
AB  - Synthesis of new non-nucleosidic phosphoramidites 1 and 2 derived from achiral
      precursors containing two reporter groups or amino functions is described. Among
      them, only phosphoramidites 1a-c allow multiple derivatization of synthetic
      oligonucleotides. The usefulness of building blocks 1a-c is demonstrated by
      introduction of several amino functions or fluorescent dansyl reporters at the 3'
      and 5'-termini of synthetic oligonucleotides and their phosphorothioate
      analogues. It is demonstrated that multilabeled non-nucleosidic tether has no or
      only minor influence on the hybridization properties of the oligonucleotides.

PMID- 8983347
TI  - Protein patterning with a photoactivatable derivative of biotin.
AB  - A method is described for the covalent immobilization of macromolecules at
      defined location on polymer surfaces. A thin film of a photoactivatable analogue
      of biotin, N-(4-azido-2-nitrophenyl)-N'-(N-d-biotinyl-3-aminopropyl)-N'-methyl
      1,3- propanediamine (photobiotin, in salt form) was dried onto polystyrene or
      nitrocellulose surfaces and then exposed to intense white light through a mask to
      yield patterns of biotin covalently bound to the polymers. The subsequent
      addition of avidin resulted in the formation of surfaces to which biotinylated
      molecules could then be bound through a biotin-avidin-biotin bridge. To develop
      the pattern of avidin on the surfaces, biotinylated enzymes (alkaline phosphatase
      and horseradish peroxidase) were specifically immobilized on the surface. These
      enzymes still retained their catalytic activities and were visualized through the
      formation of colored or fluorescent products. Various factors such as
      concentration, irradiation time, and light intensity were shown to determine the
      amount of active enzyme that could be bound and so by implication the degree of
      photobiotinylation that had occurred.

PMID- 8983348
TI  - A comparison of cleavable and noncleavable hydrazinopyridine linkers for the
      99mTc labeling of Fab' monoclonal antibody fragments.
AB  - The design and synthesis of hydrazinopyridine bifunctional chelating agents
      (BCA's) featuring amide, ester, and disulfide groups are described. The BCA's
      site-specifically react with the free thiol groups of the tumor-specific
      monoclonal antibody fragment C46.3 using a one-pot in situ reduction and
      conjugation procedure from the F(ab')2 to give Fab'-linker conjugates. Molar
      substitution ratios (MSR's) of the hydrazinopyridine conjugates were comparable
      to the theoretical (maximum) number of thiols per fragment determined by free
      hydrazine and residual thiol assays. The series of C46.3 Fab'-linker conjugates
      were 99mTc-labeled in greater than 95% radiochemical purity by incubation with
      99mTc-tricine for 1 h at room temperature. In order to evaluate the conjugates
      for radiopharmaceutical applications, the tumor localization and biodistribution
      properties of the radiolabeled Fab'-linker conjugates, compared to the direct
      labeled fragment, were tested in nude mice bearing LS174T xenografts. Depending
      upon the structure of the linker connecting the radiolabeled hydrazinopyridine
      group to the antibody fragment, we observed a variation in kidney uptake and
      whole-body clearance. Diester- and monoester-linked conjugates exhibited lower
      kidney uptake and faster whole-body clearance than the corresponding linker
      containing amide groups. This result may be interpreted as evidence for rapid
      metabolism of ester compared to amide groups in the kidney following uptake. At
      24-h postinjection, the monoester-linked conjugate 99mTc-C46.3 Fab'-BA displayed
      the highest tumor: blood ratio (16.2) compared to the directly labeled conjugate
      (6.6) and is therefore a potential clinical candidate for imaging breast and
      ovarian cancer.

PMID- 8983350
TI  - Synthesis of norbiotinamine and its derivatives.
AB  - Synthesis of norbiotinamine (II) and its reactive derivatives, isothiocyanates
      (III and IV), iodoacetamide (V), and maleimide (VI), are described. In addition,
      N-norbiotinyl-gamma-L-glutamylamide (VII) was prepared as a potential alternative
      to the fixable polar tracer biocytin (biotinoyllysine).

PMID- 8983349
TI  - Benzoylecgonine hydrazides: synthesis, coupling to horseradish peroxidase, and
      characterization of the conjugates.
AB  - Benzoylecgonine-horseradish peroxidase conjugate (BE-HRP) can be used as a
      diagnostic reagent for the detection of cocaine in illicit drug samples and in
      biological fluids. This paper describes the preparation and characterization of
      BE-HRP. Two hydrazide derivatives of benzoylecgonine, N-2-(tert
      butyloxycarbonyl)benzoylecgonine hydrazide and mono(N-2'-benzoylecgoninoyl)adipic
      dihydrazide, were synthesized by carbodiimide-activated coupling of
      benzoylecgonine to N-2-(tert-butyloxycarbonyl) hydrazide and adipic dihydrazide,
      respectively. Removal of the tert-butyloxycarbonyl protecting group in N-2-(tert
      butyloxycarbonyl)benzoylecgonine hydrazide with anhydrous HCl yielded
      benzoylecgonine hydrazide hydrochloride. NMR and high-resolution mass spectral
      analyses demonstrated that the benzoyl group of benzoylecgonine remained intact
      under the conditions of both carbodiimide coupling and anhydrous HCl treatment.
      By aldehyde-hydrazide condensation, the hydrazides were covalently conjugated to
      the carbohydrate residues of horseradish peroxidase (HRP). Dot blot analysis of
      the conjugates employing antibodies specific to benzoylecgonine demonstrated the
      presence of bound benzoylecgonine in HRP. The stoichiometry of benzoylecgonine
      residues to HRP was determined by matrix-assisted laser desorption/ionization
      mass spectrometry (MALDI-MS). Mono(N-2'-benzoylecgoninoyl)adipic dihydrazide gave
      a 2.5-3-fold higher coupling compared with benzoylecgonine hydrazide. Conjugates
      were also prepared by the coupling of the carbodiimide-activated benzoylecgonine
      to HRP that was derivatized with adipic dihydrazide.

PMID- 8983352
TI  - [50 years from the reopening of the Univeristy of Zulia (LUZ) and its Faculty of
      Medicine].

PMID- 8983351
TI  - A convenient method for the preparation of hapten phosphoramidites.
AB  - Automated incorporation of haptens at the 3' or 5' end of oligonucleotides
      required the preparation of the corresponding hapten phosphoramidites. The
      requisite 1,3-diol framework was prepared in two steps from a carboxylic acid
      precursor first by a two-carbon homologation using Meldrum's acid to form the
      corresponding 3-oxo ester and then subsequent reduction to the diol. The primary
      alcohol was protected with a dimethoxytrityl group, while the secondary alcohol
      was converted to the reactive phosphoramidite.

PMID- 8983353
TI  - [Leydig cell function in hyper- or hypoprolactinemic states in healthy men].
AB  - In the present investigation the function of the Leydig cells, as the response of
      gonadal steroids to the injections i.m. of 2000 UI of hCG, was studied in 11
      normal men, before and after the induction of hyper or hypoprolactinemia with
      sulpiride and bromocriptine treatments respectively. The normal response to hCG,
      showed an increment of serum estradiol concentration 24 h and another of serum
      testosterone 72 h after the administration of the gonadotropin. The serum FSH
      concentration decreased during the test. An increase of serum LH levels was
      observed in the hypoprolactinemic state, but the increment of estradiol was lower
      after injection of hCG. On the other hand, the hyperprolactinemia induced a low
      basal level of testosterone with a higher response of this steroid to hCG. The
      results suggest that hyperprolactinemia interfers the estradiol synthesis by
      Leydig cells while the loss of the trophic effect of prolactin on gonadal
      steroidogenesis, as seen in hypoprolactinemia produces a decrease of basal
      testosterone levels without any alteration of the response of this steroid to
      hCG. We conclude that prolactin plays an important role in the steroidogenesis of
      Leydig cells in normal men.

PMID- 8983354
TI  - [Chronic myeloid leukemia. Karyotype changes].
AB  - Chronic Myeloid Leukemia (CML) is a clonal disease of bone marrow,
      citogenetically characterized by the presence of the Philadelphia chromosome
      (Ph). Additional anomalies in the Ph cromosome have been found during the
      evolution of CML. This paper will show evidence of cytogenetic abnormalities
      during the evolution of CML in this region, and its correlation with clinical
      evolution. 55 samples of bone marrow, 81.3% (45/55) in chronic phase (CP), 12.7%
      (7/55) in an accelerated phase (AP), and 5.4% (3/55) in blastic phase (BP) were
      received. In 12/45 patients in CP the karyotype was repeated at least once a year
      during the evolution of their illness. 9/12 presented the Ph chromosome as a
      single anomaly at the moment of diagnosis; the other 3 presented a distinct
      anomaly. 4/9 presented additional abnormalities moving to the stages AP or BP
      between 4-8 months after initial discovery. 7/10 patients referred in AP or BP
      presented additional abnormalities in the Ph chromosome. It is evident that the
      chromosome study of each patient with CML must be carried out at least once a
      year in order to detect chromosomal abnormalities in addition to the Ph
      chromosome. Thus, a greater therapeutic control of the disease is possible.

PMID- 8983356
TI  - [Leigh's encephalopathy (subacute necrotizing encephalopathy). Documentation of
      its evolution through neuroimaging].
AB  - A 30 months-old boy developed bilateral nistagmus, tremor, gait disturbance,
      hypotonia and disartria. The diagnose of Leigh encephalopathy was suggested on
      the basis of clinical, neuroimaging and laboratory findings. Computed tomography
      and magnetic resonance imaging (MRI) at an early stage revealed bilateral and
      symmetric lesions in the putamen, appearing as hyperintense signal on T2-weighted
      images. Twelve months later a relatively large hypertense area in the posterior
      brainstem was observed. At this stage, the patient exhibited marked
      deterioration, dystonic manifestations, rigidity and respiratory disturbances. He
      died 6 months later for respiratory arrest during bronconeumonic infection. We
      believe MRI is a valuable means to allow assessment of the evolution of the
      disease.

PMID- 8983355
TI  - [Hypertriglyceridemia following treatment with interferon alpha in essential
      thrombocythemia].
AB  - A case of essential thrombocytemia treated with alpha interferon is reported,
      with hematological remission, but as a side effect hypertriglyceridemia is
      relevant. It was normalized when alpha interferon was stopped. This is the first
      case of essential thrombocythemia in Venezuela treated with biological modifiers,
      with hematological remission, but with hypertriglyceridemia as side effect.

PMID- 8983357
TI  - [Infection by hepatitis virus among the indigenous populations of South America:
      a review of the problem].
AB  - After the report of the epidemic outbreak of delta hepatitis among the Yukpa
      amerindians in the early 80s, the viral hepatitis arose as an important health
      problem in all the Amerindian communities from the north of South America and the
      Amazonian Basin. Despite the few data available, the results obtained in
      different communities from Venezuela (Yukpa, Bari, Yanomami) have shown a high
      endemicity of hepatitis B and D virus infections and a significant prevalence of
      hepatitis E virus-specific antibody among their members. By contrast, the
      infection by hepatitis C virus, which is present in all the urban areas from
      South America, seems uncommon, or even absent among some Amerindian populations.
      At the moment, a satisfactory explanation for this findings has not yet been
      arised. However, it could be possible that the margination of these populations
      regarding the health care system has been keeping them free of an infection
      largely linked worldwide to iatrogeny. Vaccination of Amerindian populations
      against hepatitis B should be taken as a priority of the health care programs.
      Moreover, such programs should consider the iatrogenic transmission of the HCV as
      a matter of concern regarding such populations, since parenterally transmitted
      hepatitis viruses seems to spread quickly among their members once they are
      introduced, giving rise to serious health problems.

PMID- 8983358
TI  - Papers from the 5th International Symposium on Drug Analysis. Leuven, Belgium,
      September 1995.

PMID- 8983359
TI  - Award of the Felix Hoppe-Seyler Prize of the German Society for Laboratory
      Medicine and the Gabor Szasz Prize of the German Society for Clinical Chemistry.

PMID- 8983360
TI  - [Pleural thickening in pleural tuberculosis].

PMID- 8983361
TI  - [Factors associated with pleural thickening in pleural tuberculosis. Review of 99
      cases].
AB  - OBJECTIVE: To analyze which factors were related to the development of pleural
      thickening in pleural tuberculosis (PT). METHODS: We reported 99 patients
      diagnosed as having PT separated into two different groups according to the
      presence of radiographic pleural thickening after completing the treatment:
      normal chest roentgenogram (group 1) or pleural thickening (group 2). We
      compared: clinical history, chest radiography, pleural fluid analysis,
      microbiological studies and effects of the treatment. RESULTS: 35 cases in group
      1 (35.35%) and 64 in group 2 (64.45%). All the compared results did not differ
      between the two groups, excluding a higher incidence of febrile cases, increased
      white cell count and decreased relative percentage of pleural lymphocytes in
      group 1, and increased number of cases with hemoptysis, positive sputum cultures
      in patients with parenchymal infiltrates, relative percentage of pleural
      lymphocytes and decreased white cell count in group 2. CONCLUSIONS: We reported
      an elevated incidence of residual pleural thickening, but it is unlikely that all
      the cases could have any clinical significance. We didn't confirm a
      characteristic pattern. Our findings suggested that a different reaction related
      or not to the hypersensitivity, rather than the inflammatory response to
      infection was the responsible for the fibrosis.

PMID- 8983362
TI  - [Diagnostic utility of carcinoembryonic antigen, neuron-specific enolase and
      squamous cell carcinoma antigen in malignant pleural effusion].
AB  - We evaluated the diagnostic utility of the carcinoembryonic antigen (CEA), neuron
      specific enolase (NSE) and squamous cell carcinoma antigen (SCC Ag.) in malignant
      pleural effusion (MPE). CEA, NSE and SCC Ag, blood and pleural levels were
      quantified by enzyme immunoassay (EIA) in 85 patients with pleural effusions: 35
      non malignant pleural effusions, and 50 MPE; 42 with lung carcinoma (LC), and 8
      with extrapulmonary carcinoma. The sensitivity and specificity was compared to
      cytological results of the pleural fluid. The sensitivities of CEA7 NSE and SCC
      Ag. (in pleural fluid) were 59.5%, 48.7% and 16.7% respectively in patients with
      LC (specificity higher than 90%). Using a combination with CEA and NSE, the
      sensitivity reached 80.9% (specificity, 91.4%). The cytology of pleural fluid was
      positive in 45.2%. The pleural/blood ratios did not improve the diagnostic
      performance. In patients with extrapulmonary carcinoma, the sensitivity of these
      tumor markers was lower. The combination of CEA and NSE pleural levels is useful
      in the diagnostic approach to the patient with pleural effusion. A high level of
      NSE is suggestive of small cell lung cancer (SCLC).

PMID- 8983363
TI  - [Efficiency of bone marrow aspirate for diagnosis of opportunistic infections in
      HIV infected patients].
AB  - AIDS is the first cause of opportunistic infections. The objective of the present
      study was the evaluation of the efficiency of bone marrow aspirate (BMA) for
      diagnosis of opportunistic infections in HIV infected patients with prolonged
      fever. Charts from 92 patients with BMA from 1992 to 1994 were reviewed.
      Diagnosis was achieved in 14.1% of cases. Diagnosis cannot be made by other
      methods in six leishmaniasis and in two disseminated tuberculosis. The
      sensibility was of 33.3% for mycobacterial infections, the sensibility of
      hemoculture was of 50%. The hemoglobin level was lower for patients with
      diagnostic BMA than for patients with not diagnostic BMA (77 g/l vs 97 g/l, p <
      0.0004). The WBC counts was not different in both groups of patients, and
      platelets counts was greater in patients with BMA diagnostic (165 x 10(9)/l vs
      102 x 10(9)/l, p < 0.001). In the patients with hemoglobin lower than 100 g/l the
      diagnostic efficiency was 18.6% (11 of 59 cases). The BMA was unprofitable in HIV
      infected patients with prolonged fever without hemocytopenias. Profitability
      increase in patients with hemoglobin lower than 100 g/l. The BMA in useful for
      leishmania identification. The hemoculture has greater sensitivity than BMA for
      the diagnosis of mycobacterial disseminated infection.

PMID- 8983364
TI  - [Delay time to arrive at the hospital of 275 patients with acute myocardial
      infarction. Study form the province of Teruel (1991-1994)].
AB  - BACKGROUND: To study the delay time to arrive of the hospital and its relation
      with any variables, of patients with acute myocardial infarction from the
      province of Teruel (Spain). PATIENTS AND METHODS: A prospective study was carried
      out from January 1991 to October 1994. We included patients who were
      diagnosticated of the acute myocardial infarction (212 men and 63 women). We
      considered the time between the thoracic pain and their arrive at the urgency
      service. We based the diagnosis in clinical, electrocardiographic and enzymatic
      criteria. RESULTS: The mean delay time was 8 h 46 m. The 66.5% arrives before 6
      hours. We found no differences between rural or urban patients. The delay time
      was minor in men than women (7 h 12 m versus 14 h, p = 0.0019), in younger (< 65
      years old) than in the older (6 h 3 m versus 10 h 18 m, p = 0.0278), and in those
      who were admitted to the ICU (7h 16 m versus 20 h 33 m, p = 0.0001). Was longer
      in patients with arterial hypertension and diabetes. Was minor in patients with
      dyslipemia and tobacco habit. Many patients to arrive of the hospital by
      physician order and with own vehicles, it took less time arrive at the hospital
      than by ambulance (8 h 30 m versus 18 h, p < 0.05). The medium delay in the
      emergency area was 2 h 35 m. The delay time was longer in patients who died (16 h
      versus 7h 30 m, p = 0.0018) and in those who present more frequently cardiac
      failure. CONCLUSIONS: The mean delay time to arrive at the hospital in patients
      with acute myocardial infarction from the province of Teruel (Spain) in
      unreasonable and in takes a poor prognosis, so we consider necessary to study the
      causes of this delay in order to correct them.

PMID- 8983365
TI  - [Long term survival in an HIV-immunosuppressed patient treated with foscarnet].
AB  - An HIV-infected woman with a CD4+ T-cell count below 100 x 10(6)/l survived for
      longer than 4 years of being diagnosed of AIDS, with acceptable health status
      (Karnofsky > 80%). Administration of foscarnet during two years, recommended as
      suppressive therapy for a previous cytomegalovirus retinitis, might have caused a
      sustained reduction in plasma HIV-RNA, contributing to her long-term survival.

PMID- 8983366
TI  - [Ocular toxoplasmosis in human immunodeficiency virus infected patients without
      concurrent central nervous system infection. Report of two cases].
AB  - Ocular toxoplasmosis is an uncommon complication of acquired immunodeficiency
      syndrome (AIDS), and it is generally described associated with central nervous
      system (CNS) lesions. We describe two cases of ocular toxoplasmosis in human
      immunodeficiency virus (HIV) infected patients, without concurrent CNS infection.
      Both developed bilateral or unilateral choriorretinitis with favorable response
      to antitoxoplasma therapy. None of them presented toxoplasmosis of the CNS
      coexisting with ocular lesions. Ocular toxoplasmosis should be considered in HIV
      infected patients although no involvement of the CNS is found.

PMID- 8983367
TI  - [Carbon tetrachloride poisoning].
AB  - Cases of severe acute carbon tetrachloride poisoning are sporadically described
      in Spain. We report the cases of three patients that inhaled toxic vapour of
      carbon tetrachloride that they used as a solvent during their working activity.
      They developed hepatic disfunction and one of them acute renal failure. The
      interval between the labour exposure and the medical care was higher than 24
      hours. All the patients received N-acetylcysteine treatment (300 mg/kg) and
      oxygen. The patient ith renal failure recurred hemodialysis. The basic aspects of
      diagnosis and treatment are commented.

PMID- 8983368
TI  - [Retroperitoneal hematoma after percutaneous transluminal coronary angioplasty].
AB  - An 80-years-old woman was admitted to our hospital because of unstable angina.
      The coronariography showed three-vessel coronary artery disease. The patient
      denied revascularization with coronary artery bypass surgery and coronary
      angioplasty (PTCA) was performed over two vessels with success. Within the
      following days, the patient began with pain suggesting femoral nerve compression
      and a decrease of the hematocrit without external bleeding. A computed tomography
      (CT) scan was performed to confirm the suspicion of retroperitoneal hematoma.
      This a rare complication of coronary angioplasty but it's important to remember
      because its increment during last years.

PMID- 8983369
TI  - [Pseudotumor in the forearm caused by focal myositis. A rare form of idiopathic
      inflammatory myopathy].
AB  - Focal myositis is a rare form of idiopathic inflammatory myopathy. We describe an
      additional case of focal myositis in a 54-years-old woman presenting as a painful
      pseudotumor of the left forearm. Muscle enzymes were normal but generalized
      electromyographic abnormalities were found. We consider that focal myositis is a
      heterogeneous clinical syndrome, and the cases showing only focal involvement can
      be different from those that evolve into polymyositis.

PMID- 8983370
TI  - [Thiazide diuretics and calcium metabolism: role in renal lithiasis and
      osteoporosis].
AB  - Thiazidic diuretics are first line drugs for treatment of hypertension, due to
      their proven capacity to reduce cardiovascular morbidity and mortality in
      hypertensive subjects, including the elderly. In addition, they are very useful
      in the treatment of heart failure and volumen overload in liver and renal
      diseases. On the other hand, diuretics are efficacious to prevent calcium-related
      renal stone formation with or without accompanying hypercalciuria. Finally,
      related to their capacity to reduce urinary calcium excretion they prevent
      postmenopausal and senile bone mass loose, and reduce the incidence of hip
      fracture with relevant socioeconomic consequences.

PMID- 8983371
TI  - [Triple autoimmune association in man: Sjogren's syndrome, systemic lupus
      erythematosus and primary biliary cirrhosis].

PMID- 8983372
TI  - [Chronic diarrheic syndrome from Blastocystis hominis].

PMID- 8983373
TI  - [Disseminated nocardiosis associated with HIV infection].

PMID- 8983374
TI  - [Hemoperitoneum as the first manifestation of ileal leiomyoma].

PMID- 8983375
TI  - [The association of hypopituitarism with Arnold-Chiari malformation and optic
      nerve meningocele].

PMID- 8983376
TI  - [Sepsis due to Streptococcus pyogenes].

PMID- 8983377
TI  - [Sjogren syndrome and hepatitis c virus infection].

PMID- 8983378
TI  - [The Cochrane collaboration].

PMID- 8983379
TI  - [Dyslipemia in a population with a high rate of cardiovascular mortality].
AB  - OBJECTIVE: To investigate the prevalence of dyslipaemias and the mean
      concentration of cholesterol in the blood of a specific community in a county
      which has double the rate of mortality from cardio-circulatory disease than the
      rate observed in the rest of Catalonia over the same period of time. DESIGN: A
      descriptive and retrospective study. SETTING: The Pallars Sobira Health District
      (Lieida). PATIENTS: 1,131 patients with primary care medical records, aged 20 or
      over, with two consecutive blood analyses, included in the 1991 census and with
      six inclusion criteria. Variables were age, total cholesterol and triglycerides.
      Calculation of sample variance and Student's test were used. MEASUREMENTS AND
      MAIN RESULTS: 586 patients between 20 and 64 (group I) and 545 over 65 (group II)
      were included. The results were: hypercholesterolaemia (cholesterol figure limit:
      250 mg/dl) as the commonest dyslipaemia with overall prevalence of 43.32%, and a
      mean concentration of cholesterol in blood (mg/dl) of 234 for group I; and 242
      for group II. CONCLUSIONS: 1) The prevalence of hypercholesterolaemia roundly
      exceeds the average recorded across Catalonia. 2) The mean concentration of
      cholesterol in blood is a long way above the objectives for the year 2000 defined
      in the Health Plan for Catalonia.

PMID- 8983380
TI  - [Analysis of mortality trends of ischemic heart disease in Andalucia (1975
      1992)].
AB  - OBJECTIVE: To describe the evolution of mortality due to ischaemic heart diseases
      in Andalucia between 1975 and 1992 and predict rates up to the year 2000. DESIGN:
      Descriptive study. SETTING: The Autonomous Community of Andalucia. Patients and
      other participants. Deaths because of ischaemic heart diseases between 1975 and
      1992 were obtained. MEASUREMENTS AND MAIN RESULTS: The direct method was used for
      the standardisation of mortality rates for age and sex, with the European
      population as the standard. Logarithmic transformations of the standardised rates
      for mortality due to ischaemic heart diseases for both sexes were performed and
      the regression lines were adjusted. Between 1975 and 1992 the theoretical rates
      went down both in men and women. If the same tendency were maintained, we would
      expect to see a moderate reduction between 1992 and 2000 in men and in women.
      CONCLUSIONS: The tendency of mortality due to ischaemic heart diseases in
      Andalucia is downwards in both men and women.

PMID- 8983381
TI  - [Validity and reliability of the family Apgar family function test].
AB  - OBJECTIVE: The aim of this study is to analyse the validity and reliability of
      the Apgar family questionnaire on family function. DESIGN: A crossover and
      descriptive study. SETTING: Urban health centre. PATIENTS: 656 patients of the
      Zaidin-Sur health centre in Granada were interviewed at home. The questionnaire
      was repeated an average of 6 days later to 60 of the patients (30 with an
      interviewer and 30 filling in their own). MEASUREMENTS AND MAIN RESULTS: The
      within-class correlation coefficients for the 5 items in the Apgar-family we over
      0.55, both for self-filled and interviewer questionnaires; the scale coefficients
      were 0.86 and 0.81, respectively. Item-scale correlation varied between 0.61 and
      0.71. Crombach's alpha was 0.84 and none of the items, when taken out of the
      scale, increased the alpha. The factorial analysis isolated only one factor. 16%
      of the sample had dysfunctional Apgar-family: the average score was 8.4. After
      adjustment (multiple logistic regression), the following were significantly
      linked to family dysfunction: lack of social support; being widowed or
      separated/divorced; greater perception of susceptibility to, or seriousness of,
      illness; being an over-user of the health service; and being a woman.
      CONCLUSIONS: The Apgar-family questionnaire on family function is valid and
      reliable.

PMID- 8983382
TI  - [Thematic and methodological analysis of investigation in primary care (1988
      1992)].
AB  - OBJECTIVE: To describe Spanish scientific output in primary care with regard to
      subjects, design and statistical methods employed and also its appropriateness,
      importance and funding. DESIGN: Descriptive, longitudinal and retrospective
      study. SETTING: Spanish scientific output in primary care published in medical
      journals and listed in the Indice Medico Espanol during the five year period 1988
      1992. MATERIAL: 446 original articles published in thirty-four journals.
      MEASUREMENTS AND MAIN RESULTS: The greatest percentage of articles came under the
      heading "policy and health" (23.6%), next was "health services" (14.8%). There
      was a predominance of observational designs (79.9%) and within this category,
      descriptive studies (67.1%). The most common statistical methods used were
      contingency tables (35,9%). The majority of articles (94.8%) do not indicate the
      source of their funding. The appropriateness was around 50% and the importance
      around 4%. CONCLUSIONS: According to our study, research into primary care
      centres on the evaluation and organization of the health services. The majority
      of the designs have little inferential power and simple statistical methods.
      There is hardly any funding available, and only a half of the articles comply
      with appropriateness criteria.

PMID- 8983383
TI  - [Scientific information of health personnel: an approach to the sources, access,
      costs and research].
AB  - OBJECTIVE: To study what general sources of information health professionals
      working in primary care use, their access to them, expenditure incurred in health
      information and whether they do research and publish it. DESIGN: A descriptive
      crossover study using an anonymous questionnaire. SETTING: Primary care.
      PARTICIPANTS: Doctors, paediatricians, nurses and midwives working in the primary
      care field in Area 13 of the Community of Valencia. 163 out of 255 people polled
      replied (63.9% participation). MEASUREMENTS AND MAIN RESULTS: The main sources of
      information favoured are courses and clinical sessions. 83.5% of professionals
      had done some course or attended a congress or workshop over the two previous
      years. 78.9% of staff had needed to look for a book or magazine outside their own
      library and mainly looked outside the Health Centres. 20.8% spent no money on
      health information. 34.4% had done research work: 24 doctors and 9 nurses had
      published. 14.7% felt supported always or often by their health area to do
      research. 64% did not have a wordprocessor and 71% did not have a library.
      CONCLUSIONS: The staff surveyed prefer courses and clinical sessions as their
      sources of information, which might imply little active searching for
      information. They believe that they need material and information resources for
      research work, and that incentives must be offered. Workplaces contain few
      sources of information.

PMID- 8983384
TI  - [Validity of recording preventive activities in medical histories: consumption
      and antismoking counseling].
AB  - OBJECTIVE: To compare the percentage of tobacco consumers obtained by checking
      Primary care clinical notes (PCCN) with the percentage obtained by a telephone
      poll of the same people. To compare the record of tobacco counselling in the PCCN
      with that discovered by polling. DESIGN: Crossover and descriptive study.
      SETTING: Two urban health districts. PATIENTS: Random sample of 450 with PCCN and
      between 15 and 75 years-old. MEASUREMENTS AND RESULTS: A telephone questionnaire
      with data on tobacco consumption and smokers' perceptions of anti-tobacco
      counselling. Data obtained from checking the PCCN were: age, gender, basic care
      unit, number of attendances, pathologies and related risk factors, tobacco
      consumption and counselling. Tobacco consumption did not figure in 51% of the
      PCCN. Out of the 108 smokers identified by telephone polling, only 61 had this
      fact in their PCCN. 55 of these smokers said they had been counselled, which was
      only recorded on 11 occasions in the PCCN. The probability of receiving
      counselling increased when patient was over 45, when there were pathologies or
      related risk factors, with frequency of attendance and with each daily cigarette
      smoked. CONCLUSIONS: The PCCN substantially under-record tobacco consumption and,
      especially, counselling. The smokers who receive most counselling are those have
      already, most probably, smoked for a long time.

PMID- 8983385
TI  - [Bacteriology and resistance in ambulatory urinary infections].
AB  - OBJECTIVES: To discover the bacteriological profile of urinary tract infections
      (UTI) in our out-clinic environment and their resistance to the most common
      antibiotics. DESIGN: A descriptive, retrospective study. SETTING: Ciudad Real
      Health Area (300,000 inhabitants). PARTICIPANTS: All the urine samples from the
      out-clinics referred to the microbiology lab for possible UTI in 1994 were
      included. MEASUREMENTS AND MAIN RESULTS: 3,522 cultures were studied, of which
      241 were contaminated (7%), 2,870 negative (81%) and 409 positive (12%).
      Breakdown of bacteria: E. coli (248; 60%), enterococci (38; 9%), P. mirabilis
      (25; 6%), K. pneumoniae (20; 5%), S. epidermidis (11;3%), S. saprophyticus (8;
      2%) and 61 others (15%). We found high sensitivity in the Gram-negatives to
      cephuroxim and amoxicillin-clavulanic. We observed widespread resistance,
      especially by E. coli, to quinolones, pipemidic acid and nitrofurantoin.
      CONCLUSIONS: E. coli is the micro-organism which most often causes UTI in our
      environment. We found enterococci were isolated more and S. saprophyticus less
      than in the series consulted. We found a considerable increase in resistance to
      some antibiotics often used in out-clinics for UTI treatment.

PMID- 8983386
TI  - [Modification of the vaccination technique with DTP in nursing infants after 1
      intervention].
AB  - OBJECTIVES: To evaluate alterations in techniques of DTP vaccination of nursing
      children after a two-year intervention and analyse the reasons for reluctance to
      change the norms. DESIGN: A longitudinal and prospective study, with intervention
      before and after. Evaluation through two anonymous questionnaires of staff in
      charge of the vaccinations: a general survey for each centre and an individual
      one for each nurse. SETTING: Primary care. PARTICIPANTS: The professionals in
      charge of vaccinations of nursing children in the 13 health centres and clinics
      in areas 11 and 12 of the Valencian Community in 1993. INTERVENTION: Informative
      meetings with paediatricians and nurses to pass on the recommendations of experts
      on vaccination techniques, supported by written information to the person in
      charge of vaccinations at each centre. MEASUREMENTS AND MAIN RESULTS: Out of the
      13 centres 12 returned the general survey in 1993 and 11 in 1995. The individual
      questionnaire was returned by 49 nurses. From the 12 centres injecting in the
      gluteus in 1993, 5 changed to the thigh and all now use 25 mm-long needles. The
      reasons for not changing the site of the injection were basically the greater
      number of side-effects and that the paediatricians did not consider it necessary.
      CONCLUSIONS: Vaccination techniques are usually altered after the intervention,
      though still not sufficiently.

PMID- 8983388
TI  - [Evaluation of seminars on international criteria for medical certification of
      cause of death].
AB  - OBJECTIVE: To evaluate the efficacy of seminars on the international criteria for
      medical certification of the causes of death. DESIGN: A pre-test/post-test
      evaluation, with no reference group. SETTING: A primary care health district in
      Andalusia, Spain. PARTICIPANTS: The 44 doctors in this district. INTERVENTION:
      Training seminars and evaluation of the filling-in of the Statistical Decease
      Forms (SDF) during the six months after the seminar. MEASUREMENTS AND MAIN
      RESULTS: Four quality indicators were used to assess doctors' filling-in of the
      SDFs, which contain the international criteria for certification of the causes of
      death, six months before and six months after the holding of the seminars. The
      results were then compared. In 11.4% the legibility of the hand-writing improved;
      and in 16.5% there was less confusion between the mechanism of death and the
      cause. The clinical sequence of causes reported and the indicator of more than
      one diagnosis per line did not vary significantly. CONCLUSIONS: Although the
      seminars on international norms of certification are necessary in order to
      improve the standard of mortality statistics, a change in the ways of certifying
      causes of death requires ongoing commitment to the training of certifying
      doctors.

PMID- 8983387
TI  - [Do we adequately use the sphygmomanometer for improving the prevention of
      arterial hypertension in primary care?].
AB  - OBJECTIVE: To assess the monitoring of arterial pressure (AP) in non-hypertensive
      patients at a health centre and to compare the results of two types of
      consultations. DESIGN: A retrospective observation study over 5 years. SETTING:
      Urban health care. PATIENTS: After the exclusion of hypertensive patients, 337
      medical records, which were active over the period under assessment, were chosen
      by systematic sampling of the adult population. Consultation types were: CT1
      (stable staff, MIR training, habitual development of the PAPPS); CT2 (staff not
      stable, training uneven, without systematic development of the PAPPS). Records
      were considered indicated when they contained symptoms suggestive of AHT or when
      AP had been measured because the patients had been included in a health
      programme; the rest of the records were considered not indicated. Data were
      analysed using the Chi-squared test. MEASUREMENTS AND RESULTS: 152 of the 337
      records belonged to CT1 and 185 to CT2. In 151 records there was no measurement
      of AP: 50 belonging to CT1 and 101 to CT2. 508 measurements of AP were performed,
      274 in CT1 and 234 in CT2. Of the 151 cases where measurements were not indicated
      (64 in CT1 and 87 in CT2. CONCLUSIONS: The percentage of patients without any
      monitoring is high (44.8%), similar to the percentage of AP measurements not
      indicated, which would imply the need to rationalise use of the sphygmomanometer
      in the consulting-room. CT1 consultations seem to have the most rational
      measurements of AP.

PMID- 8983389
TI  - [What is the prevalence of elderly persons at high risk in primary care?].
AB  - OBJECTIVES: To find the prevalence in a Health District of elderly people at high
      risk and the reasons for their inclusion in this category. To evaluate the
      percentage of patients requiring home care. DESIGN: A crossover descriptive
      study. SETTING: Urban health centre. PATIENTS:  STUDY POPULATION: patients over
      65, TARGET POPULATION: elderly people with their medical notes at our centre.
      SAMPLE: 329 individuals chosen by systematic sampling of everyone over 65.
      MEASUREMENTS AND MAIN RESULTS: The elderly person is defined as at high risk or
      fragile when he/she fulfils one of the following criteria: a recent hospital
      release, physical incapacity, mental deterioration, over 80, in an institution,
      confinement to the home, living alone or being widowed, and recent change of
      home. There was 38.07% prevalence of elderly people at high risk. The main
      reasons for classification as elderly people at high risk were: age over 80,
      living alone and physical incapacity. There is a significant link between being
      an elderly person at high risk and female. 31.7% of elderly people at high risk
      have a physical incapacity which prevents their attendance at the health centre.
      CONCLUSIONS: It needs to be bome in mind that almost 40% of the over-65s are
      included in the groups of elderly people at high risk and therefore need special
      attention from Primary Care professionals. Our organisation needs to be adapted
      to the growing demand for home visits, which should cover at least 12% of those
      over 65 and 31% of the fragile elderly.

PMID- 8983390
TI  - [Monitoring the use of drugs for improving the quality of prescribing. Problems,
      methods and indicators].

PMID- 8983391
TI  - [The "almost" generation].

PMID- 8983392
TI  - [Apropos of human scabies].

PMID- 8983393
TI  - [Pellagra in alcoholic patients].

PMID- 8983394
TI  - Pharmacokinetics of DA-125, a new anthracycline, after intravenous administration
      to uranyl nitrate-induced acute renal failure rats or protein-calorie
      malnutrition rats.
AB  - The pharmacokinetics of DA-125 were compared after intravenous (i.v.)
      administration of the drug, 10 mg kg-1, to control male Sprague-Dawley rats (n =
      9) and uranyl nitrate-induced acute renal failure (U-ARF, n = 12) rats, or male
      Sprague-Dawley rats fed on a 23% (control, n = 8) or a 5% (protein-calorie
      malnutrition, PCM, n = 9) protein diet. After i.v. administration of DA-125,
      almost 'constant' plasma concentrations of M1, M2, and M4 were maintained from 1
      2 h to 8-10 h in all rat groups due to the continuous formation of M2 from M1 and
      M4 from M3. The plasma concentrations of M3 were the lowest among M1-M4 for all
      rat groups due to the rapid and almost complete conversion of M3 to M4 and other
      metabolite(s). The AUCt values of M1 (115 against 82.5 micrograms min mL-1), M2
      (33.0 against 23.6 micrograms min mL-1), and M4 (26.3 against 15.1 micrograms min
      mL-1) were significantly higher in the U-ARF rats than in the control rats. The
      percentages of i.v. dose excreted in 24 h urine as M1 (under the detection limit
      against 0.316%), M2 (under the detection limit against 5.58%), and M4 (0.0174
      against 0.719%)--expressed in terms of DA-125--were significantly lower in the U
      ARF rats than in the control rats, and this could be due to the decreased kidney
      function in the U-ARF rats. However, the percentages of i.v. dose recovered from
      the GI tract at 24 h as M1 (0.0532% against under the detection limit), M3
      (0.0286% against under the detection limit), and M4 (0.702% against 0.305%)-
      expressed in terms of DA-125--were significantly greater in the U-ARF rats than
      in the control rats. All U-ARF rats had ascites, but the concentrations of M1
      (0.0320 micrograms mL-1), M2 (0.0265 micrograms mL-1), M3 (under the detection
      limit), and M4 (0.032 micrograms mL-1) in the ascites from one rat were almost
      negligible. The plasma concentrations and most of the pharmacokinetic parameters
      of M1, M2, and M4 were not significantly different between the PCM rats and their
      control rats.

PMID- 8983396
TI  - Absorption of sulindac from a novel (Pro-SorbTM) liquid formulation.
AB  - The absorption of sulindac from two different 200 mg oral dosage forms, Pro
      SorbTM liquid and Clinoril tablets, was compared following administration to
      eight healthy human volunteers. Subjects received both formulations according to
      a randomized crossover design and blood samples were collected at selected times
      during 24 h. Concentrations of both sulindac and its active sulphide metabolite
      were determined by HPLC and individual serum concentration versus time profiles
      were constructed. Maximal serum concentrations (Cmax) and area under the curve
      values (AUClast and AUC0-infinity) were compared for both sulindac and sulindac
      sulphide. The results indicate that the rate and extent of absorption of sulindac
      from Pro-SorbTM liquid are significantly greater than those from Clinoril
      tablets, a finding consistent with the observation that the liquid form produces
      less gastric irritation following oral administration.

PMID- 8983395
TI  - Discontinuous oral absorption pharmacokinetic model and bioavailability of 1-(2
      fluoro-5-methyl-beta-L-arabinofuranosyl)uracil (L-FMAU) in rats.
AB  - 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)uracil (L-FMAU), the L isomer of
      FMAU, has shown potent activity against hepatitis B virus and Epstein-Barr virus.
      L-FMAU showed double peaks in the plasma concentration versus time profiles
      following oral administration to rats, indicating discontinuous oral absorption.
      The objective of this study was to characterize the bioavailability and pattern
      of L-FMAU absorption using a pharmacokinetic model which incorporated two
      separate absorption processes following oral administration of the nucleoside in
      an animal model, the rat. Simultaneous fitting of differential equations to L
      FMAU plasma concentrations following oral and intravenous administration was
      performed using PCNONLIN. Total clearance of L-FMAU was moderate, averaging 0.47
      +/- 0.16 L h-1 (mean +/- SD). Distributional clearance averaged 0.18 +/- 0.14 L h
      1. The volume of the central compartment averaged 0.30 +/- 0.09 L, and the volume
      of the peripheral compartment averaged 0.15 +/- 0.08 L. The first-order
      absorption rate constants describing the first and second absorption phases
      averaged 1.22 +/- 1.56 and 4.14 +/- 5.42 h-1, respectively. Oral bioavailability
      was calculated by three methods: AUC, urinary excretion data, and a discontinuous
      oral absorption pharmacokinetic model. Bioavailability averaged 0.59 +/- 0.16,
      0.64 +/- 0.23, and 0.63 +/- 0.13, respectively, for the three methods. The
      discontinuous oral absorption pharmacokinetic model is a promising new method for
      estimating absorption from two phases and for calculating oral bioavailability.

PMID- 8983397
TI  - A model based assessment of redistribution dependent elimination and
      bioavailability of rifabutin.
AB  - The autoinduction characteristic of rifabutin (RIF) following multiple oral
      dosing was investigated via pharmacokinetic modeling. A two-compartment model
      with first-order absorption was fit to plasma RIF data obtained from a study
      conducted in healthy normal volunteers following both a single and multiple oral
      doses. Parameter estimates showed an elimination rate constant (k10) of about
      0.12-0.14 h-1 which was independent of the single or multiple-dosing condition.
      The lower-than-expected drug accumulation following multiple dosing seems to
      suggest that prolonged dosing perturbs the linear kinetic system. However, this
      analysis has shown no significant changes (p > 0.05) in the rate constants
      describing RIF absorption, tissue distribution/redistribution, and elimination.
      The mean rate of drug redistribution from the tissue compartment (k21; 0.04-0.06
      h-1) was twofold to threefold lower than k10, and, with a large steady-state
      distribution volume (Vss/F after a single dose, 1630 L), RIF elimination appears
      to be dependent on drug redistribution. This hypothesis was further supported by
      a significant correlation (p < 0.01) between RIF tissue redistribution (k21) and
      terminal disposition phase rate (lambda z) constants. The redistribution
      dependent elimination of RIF also helps explain the stability of the terminal
      half-life under both single and multiple-dosing paradigms. Urinary excretion of
      RIF and its 25-O-deacetyl metabolite totalled less than 7% of the oral dose
      following single dosing, and decreased to about 4% after multiple dosing. For
      individual patients, the decrease in urinary recovery of the 25-O-deacetyl
      metabolite was directly proportional to the decrease in urinary RIF recovery. In
      addition, both estimates of the model intercepts (A and B) were lower following
      multiple dosing. Further analyses revealed a linear relationship between A and B
      intercepts, and also between the urinary RIF recovery and the B intercept. These
      relationships, in conjunction with the lack of significant increase in the rate
      of elimination, indicate that induction of presystemic extrahepatic metabolism
      and/or decrease in the extent of oral absorption may be the primary causes for
      the lower-than-expected systemic RIF plasma levels after multiple oral dosing.

PMID- 8983398
TI  - Dose-dependent distribution volumes of total and unbound valproate in guinea
      pigs: consequence of non-linear plasma protein binding.
AB  - The response of steady-state distribution volume (Vdss for total and Vdssu for
      unbound drug) of valproate (VPA) to dose-dependent plasma protein binding was
      studied in guinea-pigs. Various steady-state plasma concentrations of VPA were
      achieved by intravenous constant infusion. The concentrations of VPA in plasma
      (Css for total and C(uss) for unbound drug) and various tissues (CT) were
      determined. The Vdss and the Vdssu were estimated based upon the apparent tissue
      to-plasma concentration ratio of VPA. The results showed that the plasma unbound
      fraction (fu) of VPA increased significantly with dose. The Vdss was
      significantly increased with, while the Vdssu was significantly decreased against
      the increasing dose. The increase in Vdss with dose indicated an increase in
      tissue-to-plasma concentration ratio, which may be attributed to the increase in
      distribution of unbound drug from plasma to tissues subsequent to non-linear
      plasma protein binding. The decrease in Vdssu against the increasing dose
      indicated a decrease in tissue-to-unbound plasma concentration ratio, which
      suggests that the extravascular distribution of unbound VPA might be capacity
      limited and the tissue binding of VPA negligible.

PMID- 8983399
TI  - Pharmacokinetics and absolute bioavailability of epristeride in healthy male
      subjects.
AB  - The objective of the current investigation was to describe the pharmacokinetics
      and absolute oral bioavailability of epristeride. Twelve healthy male subjects
      (mean (SD) age, 27 (6.2) years) received a single oral dose of 5 mg and an
      intravenous infusion of 4.5 mg over 30 min in a crossover fashion. Blood samples
      were obtained over 72h for the determination of epristeride plasma concentrations
      using a sensitive high-performance liquid chromatography assay. The lower limit
      of quantification was 5 ng mL-1. Pharmacokinetic analysis of the plasma
      concentration-time data was performed by both non-compartmental and compartmental
      methods. Absolute bioavailability was determined using dose-normalized AUC values
      following oral and intravenous administration. Epristeride plasma concentrations
      declined in a biexponential fashion with secondary peaks evident around 24 h in a
      majority of subjects following both routes of administration. Maximal plasma
      concentrations were typically achieved approximately 4 h after oral dosing. The
      mean apparent terminal elimination half-life estimates were similar following
      intravenous and oral administration and were 27.3 and 26.2 h, respectively. The
      mean plasma clearance and steady-state volume of distribution were 0.33 (0.09) mL
      min-1 kg-1 and 0.54 (0.17) L kg-1, respectively. The mean absolute
      bioavailability was 93% (95% CI: 84%, 104%). Following compartmental analysis of
      the intravenous data, the mean (SD) lambda 1 and lambda 2 half-life estimates
      were 2.74 (0.48) and 31.8 (19.5) h, respectively. The % AUC associated with the
      lambda 2 exponential phase was approximately 68%. This long half-life allows for
      once-daily dosing of epristeride.

PMID- 8983401
TI  - Basic and clinical aspects of Helicobacter pylori infection. International
      symposium of Jagiellonian Medical Faculty Fundation, Cracow, Poland, December 18,
      1995. Abstracts.

PMID- 8983400
TI  - Theophylline controlled-release formulations: in vivo-in vitro correlations.
AB  - Four experimental controlled-release oral solid dosage formulations were
      developed and the in vitro dissolution characteristics of theophylline from these
      formulations were studied in USP apparatus I. Pharmacokinetic evaluation of these
      formulations was carried out in eight beagle dogs under fasting conditions.
      Theophylline in a 5% dextrose injection USP, oral solution, and Slo-Phyllin were
      used as controls to estimate the in vivo dissolution of these four formulations
      in the GI tract. The percentage cumulative amounts of drug absorbed and the
      percentage cumulative amounts of drug released into the GI tract from these four
      controlled-release formulations were obtained by numerical deconvolution methods.
      The in vivo and in vitro dissolution data demonstrated good correlation
      indicating that in vitro dissolution tests can be used to optimize the further
      design of controlled drug release oral solid dosage formulations for
      theophylline.

PMID- 8983402
TI  - [Risk factors and some pathological features in relation to the type of brain
      neurodynamic pattern].

PMID- 8983403
TI  - [Adaptation to exercises after exposure to restriction stress].
AB  - Adaptation to exercises was studied in rabbits exposed to restriction stress.
      Transition from 30-day inactivity to the routine motor activity and subsequent
      exercises was found to cause a further progression of blood atherogenic changes,
      ulcerative arteriosclerosis, and heart failure.

PMID- 8983404
TI  - [Hemolytic uremic syndrome as a clinical manifestation of oxidative stress].
AB  - An examination was made of seventeen children having various stages of the
      hemolytic uremic syndrome: Stage 1 is the period of an expanded clinical picture
      of the disease, the patients' condition is grave (anuria, azotemia, severe
      hemolytic anemia and thrombocytopenia); Stage 2 is the period of recovery. The
      plasma levels of malonic dialdehyde, dienic conjugates, alpha-tocopherol at the
      first stage of the disease were considerably higher than the control ones, on
      recovery there were their reductions though their levels remained higher than the
      normal levels. The levels of malonic dialdehyde in the red blood cell membranes
      in ill children were also much higher than those in healthy donors, but at the
      second stage they decreased, but remained high. The activity of superoxide
      dismutase in the red blood cells of ill children in the acute period of the
      disease did not significantly differ from that of donors. At the second stage of
      the disease there was a significant fall in the activity of red blood cell
      superoxide dismutase. The activity of catalase in the red blood cells of ill
      children was thrice higher than in the controls; however, this index decreased
      during treatment and at the second stage it did not differ from that in the
      controls. There were no significant differences in the activity of red blood cell
      superoxide dismutase in donors and ill children. Mechanisms responsible for
      abnormal plasma and red blood cell peroxidation are considered in the hemolytic
      uremic syndrome. It is concluded that free radical reactions play a substantial
      role in the pathogenesis of this abnormality.

PMID- 8983405
TI  - [The body's antioxidative systems in bronchopulmonary disease].
AB  - A comprehensive study was made of the parameters of antioxidative defense in
      patients with chronic nonspecific pulmonary diseases (CNSPD), malignant and
      benign respiratory tumors. The highest deficiency of antioxidants both in blood
      and lung tissues were noted in CNSPD patients. With malignant tumors, the level
      of radical inhibitors depends on the stage of malignancy and the histological
      pattern of a tumor. There were correlations between the studied parameters in the
      blood and cytoplasmic fraction of lung tissue in cancer patients. It is suggested
      that redistribution of antioxidative resources occurs in the body in
      adenocarcinoma and small-cell carcinoma.

PMID- 8983407
TI  - [Blood flow lipid transport from viewpoint of protein biochemistry].
AB  - In accordance with the principles of protein biochemistry, apolipoprotein is the
      only protein which: 1) forms a protein-lipid complex (PLC) mainly from one class
      of lipids; 2) determines its functional role; 3) causes dyslipidemia in the
      genetic destruction of apoproteins or their quantitative ratio. Blood flow lipid
      transport is based on the functional specificity of their apoproteins; each
      apoprotein forms a functionally independent PLC; each PLC is formed from one
      class of lipids; each PLC has one protein-vector; each protein-vector interacts
      only with receptor. The basis of a united cycle functioning in lipid transport is
      the difference of primary apoprotein structure. Cholesterol performs an auxiliary
      function in triglyceride transport by providing circulation in the functional
      cycle. Lipid transport in blood flow is based, first, on the principles of
      protein biochemistry and, second, on those of lipidology.

PMID- 8983406
TI  - [Comparative investigation of anticonvulsive effects of putrescine and structural
      analogues of delta-sleep-inducing peptide].
AB  - Intracysternal putrescine before a session of hyperbaric oxygenation (0.7 MPa)
      was shown to be more effective in prolonging the latent period of onset of
      generalized convulsive activity than intraperitoneal delta-sleep-inducing peptide
      or its structural analogues ID-1 or ID-3. Biochemical studies indicated that
      putrescine was also more effective in preventing hyperbaric oxygenation-induced
      decreases in the levels of GABA and homocarnosine in the brain and the
      accumulation of lipid peroxidation products in the brain and serum.

PMID- 8983408
TI  - [Design of topically resorptive interferon drugs].
AB  - The current data on the development and design of topically resorptive interferon
      drugs are summarized. In many cases it is advisable to use topically resorptive
      interferon agents which allows them to topically affect a clinical process, to
      avoid negative sequelae seen when high-dose interferon is unjustifiably
      systematically given, by reducing its use to a minimum. Interferon is known to be
      one of the best antiviral agent, besides, it produces marked antimicrobial and
      antitumor effects. Whether interferon as a component of drugs can be stabilized
      by axillaries of various chemical nature which act as stabilizers, promoters, and
      carriers is dealt with. The topically resorptive formulations designed in terms
      of biopharmaceutical factors are described. The advantages of topically
      resorptive agents over other drugs are shown and hence they can be widely used in
      practical medicine.

PMID- 8983409
TI  - [The structural status of red blood cell membranes in children with insulin
      dependent diabetes mellitus. Examination by spin probe].
AB  - Using spin probes-stearic acid analogues, the authors investigated the
      microviscosity and the a/b parameter of red blood cell membranes in children with
      diabetes mellitus. The structural changes were correlated with altered metabolic
      measurements. The change in the pathway of insulin in diabetes mellitus led to
      the structural state of red blood cell membranes.

PMID- 8983410
TI  - [Role of plasmalemma in the process of aging, elimination and reproduction of
      erythrocytes: plasmalemmal microvesicles as stimulators of erythropoiesis].
AB  - This study summarizes the experimental findings suggesting that plasmalemmal
      microvesicles formed from red blood cell aging are stimulators of erythropoiesis.
      The supposed sequence of events consists of microvesicular absorption by the
      settled macrophages of the liver and spleen, a message of information from
      circulatory monocytes (and lymphocytes) to the central macrophage of
      erythropoietic islands and regulation of late erythropoiesis. This is an
      autoerythronic regulation because it corrects red blood cell reproduction in
      relation to the rate of cell aging and thus differs from the classical humoral
      type which regulates erythrocytic reproduction according to visceral oxygen
      supply.

PMID- 8983411
TI  - [Use of parenteral feeding in the multimodality treatment of Crohn's disease and
      nonspecific ulcerative colitis].
AB  - The paper reviews publication on the use of complete parenteral feeding in the
      multimodality treatment of inflammatory bowel disease. Complete parenteral
      feeding was performed in patients with skeletization and physical retardation, in
      severe diseases, in inefficiency or intolerance of conventional therapy with
      sulfanilamides and steroids, in those who had intestinal fistulas, as well in the
      preparation of patients for surgical treatment. The use of complete parenteral
      feeding, under the above circumstances allow one to achieve persistent remission,
      spontaneous healing of intestinal fistulas, elimination of abnormal metabolism,
      nutrition, constitution, water-electrolyte balance, to reduce a surgical risk and
      the incidence of postoperative complications and the length of patients' hospital
      stay.

PMID- 8983412
TI  - [Academician FG Krotkov and development of Russian and World hygienic science].

PMID- 8983413
TI  - [Feodor Grigor'evich Krotkov and Military Hygiene (to 100 birthday anniversary)].

PMID- 8983414
TI  - [On the out-of-town meeting of the Department of Biomedical Sciences, Russian
      Academy of Medical Sciences].

PMID- 8983415
TI  - [Problems of molecular genetics of inherited diseases].
AB  - The paper reviews the basic achievements in the study of human inherited diseases
      by applying the guidelines and technology of reversed genetics, outlines the
      results of genome mapping, positional cloning of disease loci, identification of
      gene mutations and DNA diagnosis of inherited diseases. It also discusses the
      problems of molecular heterogeneity of inherited diseases and of the
      relationships between the genotype and the biochemical and clinical phenotypes of
      diseases, gives the data on identification of genetic risk factors and
      polymorphic linked markers for some common diseases, and characterizes the lines
      in the development of approaches to gene therapy for inherited diseases.

PMID- 8983417
TI  - Special issue: Professor Luis F. Leloir, 25th anniversary of his Nobel Laureate.

PMID- 8983416
TI  - Writing in English for an international readership.

PMID- 8983419
TI  - [Tetranucleotides and their phenazine derivatives as compound primers for DNA
      sequencing using Sanger method].

PMID- 8983420
TI  - [Prenatal morphogenesis of the lateral nasal gland in mammals].

PMID- 8983418
TI  - Comparison of the expression of a plastidic chaperonin 60 in different plant
      tissues and under photosynthetic and non-photosynthetic conditions.
AB  - A partial cDNA which codes for the beta-subunit of a plastidic chaperonin 60
      (cpn60-beta) from rye (Secale cereale L.) leaves was identified and sequenced,
      except for 46 amino acids of the N-terminus of the mature protein and the transit
      sequence. This is the first cpn60-beta sequence determined for a monocotyledonous
      plant. Specific antibodies against cpn60-beta were affinity-purified from an
      antiserum raised against the total soluble protein fraction of ribosome-deficient
      plastids. The localization of cpn60-beta in chloroplasts or non-green plastids
      was confirmed by immunodetection in Percoll gradient-purified organelles. The
      expression and occurrence of cpn60-beta was analysed by immunoblotting with the
      specific antibodies and Northern hybridization. The cpn60-beta protein was
      constitutively expressed in various green and non-green tissues. It was evenly
      distributed along the major part of a rye leaf, while highest transcript levels
      occurred in the youngest and oldest leaf sections. The expression of the cpn60
      beta protein was not enhanced by a heat-shock treatment at 42 degrees C. The
      cpn60-beta transcript and protein were more strongly expressed in various non
      green, for instance etiolated, 70S-ribosome-deficient 32 degree C-grown, or
      herbicide-bleached tissues, than in green leaves of rye. A rapid increase in the
      cpn60-beta transcript level was also observed when green leaves were transferred
      from light to darkness while the protein level was not affected. The dark-induced
      increase in the cpn60-beta transcript was totally suppressed in the presence of
      2% sucrose. Inhibitor treatments suggested that the change in cpn60-beta
      transcript level was not related to changes of the ATP supply of the tissue.
      While the large subunit of the photosynthetic protein ribulose-1,5-bisphosphate
      carboxylase was largely degraded during ripening of tomato fruits, high levels of
      cpn60-beta were detected in tomato chromoplasts and in the yellow flower petals
      of Narcissus. Low levels of cpn60-beta were detected in root tissue.

PMID- 8983421
TI  - [Properties of reversible Ca2+-dependent inactivation of NMDA receptor on the
      cerebellum granular cells].

PMID- 8983422
TI  - [Information stores and fluxes in biota and civilization].

PMID- 8983423
TI  - [Regions of increased density of the ganglion cells, and resolution of the retina
      of the grey whale Eschrichtius gibbosus].

PMID- 8983424
TI  - [Comparative evaluation of the genotoxic effect of complex platinum compounds in
      pro- and eukaryotic test-systems].

PMID- 8983425
TI  - [The effect of pulsed ultrasound on regeneration of locally irradiated mammalian
      skeletal muscles].

PMID- 8983426
TI  - [A novel class of small RNP (alpha-RNP) in human cell line K-562 and coordinated
      control of expression of Alu-containing messenger RNA].

PMID- 8983427
TI  - [The role of somatosensory afferents in neuroimmune reactions during exposure to
      diphtheria toxin].

PMID- 8983429
TI  - [One approach to comparison of the distribution of the prevalence of congenital
      defects in populations].

PMID- 8983428
TI  - [Mechanism of immunomodulating effect of vitamin D: possible involvement of lipid
      peroxidation system].

PMID- 8983430
TI  - [Histochemistry of phosphatases in two types of sole skin glands in various
      species of Far Eastern voles].

PMID- 8983431
TI  - [Cystathionase: catalytic activity of products of expression of cDNA fragments.
      Specific inhibition of native enzyme and fusion-protein by substrate-like O
      substituted hydroxylamine].

PMID- 8983432
TI  - [Biocompatible properties of implantable polymeric materials].

PMID- 8983433
TI  - [Effect of DNA on the ultrastructural organization of lecithin liposomes in the
      presence of calcium cations].

PMID- 8983435
TI  - [Participation of thymus cells in post-traumatic regeneration of irradiated
      skeletal muscles after their treatment with pulsed ultrasound].

PMID- 8983434
TI  - [Isolation and properties of kidney receptor protein binding nucleic acids].

PMID- 8983436
TI  - [Vaccinia virus recombinants carrying ras oncogene induce neoplastic cell
      transformation].

PMID- 8983437
TI  - [Chemotactic activity of neutrophils from atopic and non-atopic subjects--effect
      of sodium cromoglycate (DSCG)].
AB  - It has been well documented, that sodium cromoglycate (DSCG) is capable in
      inhibiting activity of several inflammatory cells putatively involved in allergic
      and non-allergic asthmatic inflammation. The goal of this study was to compare
      the effect of DSCG on random locomotion and chemotaxis of neutrophils to several
      stimuli in atopic and non-atopic subjects. In 10 seasonal asthmatic (SA), and 10
      healthy subjects (HS) chemotactic responses of neutrophils were examined using
      modified Boyden's microchamber (Neuroprobe) technique. Neutrophils isolated from
      both HS and SA demonstrated similar spontaneous migration and dose dependent
      chemotactic responses to FMLP (10(-12) - 10(-5M)), PAF (10(-7) - 10(-5M)) and ZAS
      (2.5% - 50%). DSCG in concentration range 10(-7) - 10(-9M) expressed a dose
      dependent inhibition of both random migration and chemotactic responses to all
      stimuli tested, with maximal inhibition ranging from 58%-89% and 67%-75% for HS
      and SA, respectively. Our results confirm potent anti-inflammatory activity of
      DSCG in vitro, and demonstrate, that this activity is similar in atopic
      asthmatics, and in healthy subjects.

PMID- 8983438
TI  - [Evaluation of soluble components of receptors with weak affinity for IgE (sCD23)
      in children with pollinosis given specific immunotherapy].
AB  - The aim of this study was the evaluation of the measurement of sCD23 and IgE
      levels before and after immunotherapy. The research was conducted in a group of
      23 children aged 6 to 18 years with pollinosis diagnosed on the basis of the
      patient's history, increased IgE level and positive skin tests with pollen
      allergens. The control group consisted of 10 healthy children in the same age
      with normal IgE level. The treated children were examined before and 6 weeks
      after immunotherapy. Before immunotherapy in both groups of children (with the
      high and medium IgE level) the sCD23 concentration was statistically higher
      (level of significance p < 0.001) compared to the sCD23 level in the healthy
      children. After immunotherapy we observed significant decrease of the sCD23
      level. We did not found correlation between sCD23 and IgE in children with
      pollinosis before and after immunotherapy.

PMID- 8983440
TI  - [Results of anti-tuberculosis treatment of patients with tuberculosis--children
      and adolescents treated in Poland in 1993].
AB  - Treatment of 581 new cases tuberculosis in 215 children and 366 adolescents
      reported in 1993 were followed up for 12 months. The results show that 96.6%
      bacteriologically confirmed cases were cured (93.8% of children and 97.2% of
      adolescents). Among 409 bacteriologically negative cases (183 children and 222
      adolescents) only in 7 (4 children and 3 adolescents) i.e. in 1.7% no
      radiological improvement was observed. 75.7% of cases BK+ received 4 drugs
      treatment regimen-85.4% adolescents and 40.6% children. Children with
      bacteriologically negative tuberculosis were treated with 2 drugs regimen -(53%
      of cases) and with 3 drugs regimen 43.2% of cases, while in adolescents majority
      of cases received 4 drugs (59.0%) or 3 drugs (33.8%). In almost all regiments
      there were INH and RMP. In spite of high efficacy of applied regimens, the
      duration of treatment was relatively long. In children BK+ , in 87.8% of cases it
      was longer than 6 months (in 43.8% of cases it was longer than 9 months). In
      adolescents BK+, in 81.2% of cases duration of treatment was longer than 6 months
      (in 34.7% it was longer than 9 months). Among cases BK(-), in 82.5% of children
      duration of treatment was longer than 6 months and 53.7% adolescents BK(-) were
      treated longer than 6 months.

PMID- 8983439
TI  - [Pulmonary embolism in malignancy of the lung: a retrospective clinical
      evaluation and pathomorphologic personal material].
AB  - The incidence and clinical significance of pulmonary embolism (PE) in pulmonary
      malignancy were analysed among 111 autopsy cases including: 65 primary and 24
      metastatic lung cancer, 8 hematological malignancies and 14-malignant pleural
      mesothelioma. In 34 (31%) cases PE was found, in 4 (12%) patients cancer tissue
      emboli was documented. In nonsmall cell lung cancer the frequency of PE was 40%,
      compared to 24% in small cell, 25% in metastatic lung cancer and 14% in
      mesothelioma. Deep venous thrombosis of lower extremities was the source of
      thrombotic material in 35% cases. In remaining cases the sources of thrombotic
      material were different (caval vein inferior, superior, and their main branches,
      right heart cavities, pulmonary artery). In 8 patients with PE the acute form of
      DIC was observed. In 15 (44%) patients the clinical ante mortem diagnosis of PE
      was done. In 26% of all analysed cases PE was the direct cause of death. We
      concluded that PE is a frequent and dangerous complication of lung neoplasms.
      Clinical diagnosis can be extremely difficult.

PMID- 8983441
TI  - [Is tuberculosis in children and adolescents in Poland an epidemiologic problem?
      Clinical?].
AB  - The tuberculosis incidence and mortality in children and adolescents in Poland in
      the years 1970-1994 declined very substantially. In children (0-14 years) the
      incidence in 1970 was 14.3 per 100,000, and in 1989 it was 2.0 per 100,000, with
      slight increase to 2.3 per 100,000 in the years 1990-1994. In 1994 there were 203
      cases of tuberculosis in children and 352 cases in adolescent. In adolescents
      during the whole period of 1970-1994 the incidence declined from 81.9 per 100,000
      to 11.1 per 100,000, and in both of these age groups, i.e. 0-14 and 15-19 the
      level of decline was much higher than in older age groups. It was also noted that
      in both of these groups there were more cases among girls than boys. The very
      small number of cases with clinically severe forms of tuberculosis, i.e. miliary
      tuberculosis and meningitis is further evidence of improvement of the
      epidemiological situation of tuberculosis in the whole group of 0-19 years. In
      1994, 60% of new cases among children had a close family contact, while in
      adolescent it was 15%, and in general population only 3%. Mortality from
      tuberculosis in children and adolescents was incidental only. In 1994 a death due
      to tuberculosis was reported in 1 child and 2 adolescents, while in 1950 there
      were 3056 deaths in children (11.6 per 100,000) and 1647 deaths in adolescents
      (68.2 per 100,000) of which 1500 were due to tuberculous meningitis.

PMID- 8983442
TI  - [Etiology of pleural exudates from personal material].
AB  - Etiology of pleural exudates was established in 87 (79%) out of 110 men, in age
      18-82 years, mean-51 years. In this group of patients tuberculosis was recognized
      in 19.1%, neoplastic disorders in 25.4%, infectious-nontuberculous disease in
      34.5%. Etiology of pleural exudates in 20.9% of patients was unknown. However,
      80% of them improved in the course of antituberculous treatment.

PMID- 8983443
TI  - [Level of D-dimer and comparison with cell count in pleural effusion from
      tuberculosis and neoplasms].
AB  - The examinations were carried out in 33 patients (aged 21-69 years) with
      tuberculous and neoplastic effusions, before and during the treatment. 10
      subjects with circulatory failure and pleural effusion a consisted control group.
      D-dimer level was detected using semiquantitative method (D-dimer Latex Test,
      Diagnostica Stago-Boehringer Mannheim), cells number and composition-using light
      microscope. All the groups demonstrated significant differences in the effusion D
      dimer level before and during the treatment. Cells number was significantly
      higher in tuberculous and carcinomatous pleural effusion than in the control
      group. D-dimer level correlated with neutrophils percentage only in tuberculous
      effusions before the treatment. We found no correlation in D-dimer level and
      cells number and composition in neoplastic pleural effusion. We did not find any
      correlation in D-dimer level and cells number in blood.

PMID- 8983445
TI  - [Use of intraluminal brachytherapy for treatment of patients with non-small cell
      lung cancer in cases of local failure after teleradiotherapy].
AB  - Remote afterloading high-dose-rate brachytherapy was used for the treatment in 38
      patients with non-small cell lung cancer local failure after previous
      teleradiotherapy. The high dose unit we used is called microSelectron HDR. A dose
      of 18 Gy or 22.5 Gy was delivered in three fractions repeated weekly. Before
      treatment, symptomatic occlusions were seen in all patients. After treatment
      palliative improvement was seen in 30 patients (78.9%). The average follow up
      time was 7.2 months and range from 3 to 17. Median response time was 6.8 months.
      12 patients died meanwhile. The procedure has been well tolerated with low
      toxicity. We conclude that palliative endobronchial high dose rate brachytherapy
      is a useful palliative modality in patients with recurrent endobronchial
      symptomatic carcinoma.

PMID- 8983444
TI  - [Evaluation of the usefulness of palpation and Daniel's biopsy for detection of
      metastasis to supraclavicular and scalene lymph nodes in patients with lung
      neoplasms].
AB  - In 169 patients with lung cancer the usefulness of physical examination and
      Daniel's biopsy in detection of metastases to supraclavicular and scalene lymph
      nodes were evaluated. In 35 patients with palpable lymph nodes and in 25 patients
      with nonpalpable lymph nodes metastases were confirmed by histological
      examination. The sensitivity, the specificity and the likelihood ratio of
      physical examination in detection lymph nodes metastases were respectively: 58%,
      86% and 4.1. In 6 patients (5%) among 119 with nonpalpable lymph nodes the
      positive Daniel's biopsy was the diagnostic procedure. In 5 patients with non
      small carcinoma and in 3 patients with malignant mesothelioma positive results of
      Daniel's biopsy enabled a change of cancer staging and giving up the eventual
      surgical operation.

PMID- 8983446
TI  - [Level of GM-CSF and IL-4 in serum of children with bronchial asthma].
AB  - Serum IgE, GM-CSF and IL-4 concentrations were measured in 35 children (3 to 18
      years of age) with bronchial asthma in I and II clinical stage. Control group
      consisted of 10 healthy children (6 to 9 years of age) without any symptoms of
      inflammatory process. All measurements were performed by ELISA tests. The
      concentration of serum IL-4 was statistically significantly higher in children
      with bronchial asthma (0.06 ng/ml) than in the control group (0.01 ng/ml). Serum
      concentration of GM-CSF was lower in children with bronchial asthma than in
      control group (4.4 and 8.44 pg/ml respectively).

PMID- 8983447
TI  - [Implantation of cervix neoplasms in the right heart ventricle as the cause of
      chronic pulmonary embolism].
AB  - 38-years-old female patient was referred to the Pulmonary Diseases Ward because
      of suspicion of the right lung infiltrative tuberculosis. Anamnesis included
      cervical carcinoma treated surgically two years earlier. Neither radio- nor
      chemotherapy was applied. Infectious etiology was not confirmed. Lab tests,
      bronchoscopy and abdominal USG did not show any abnormalities. Contributory
      anamnesis, cardiorespiratory failure, variability of X-ray picture, enlargement
      of the heart in subsequent X-ray examinations suggested chronic pulmonary
      embolism. Large tumor masses were seen within the right ventricule on USG
      examination. The patient died in the course of the surgical procedure. Grey
      yellow, elastic masses remaining in pulmonary arteries and between trabeculae
      carneae were found on autopsy. Enlarged and infiltrated paraaortic and iliac
      lymph nodes were observed. Planoepithelial nonkeratinizing carcinoma cells were
      confirmed in the above mentioned masses.

PMID- 8983448
TI  - [Chylopericardium and chylothorax of unknown etiology].
AB  - A case of a young man with chylopericardium followed by chylothorax was
      described. Performed diagnostic procedures did not reveal infectious, neoplastic
      or traumatic cause of chylothorax. Only partially deformed lymphatic system of
      the thorax was found.

PMID- 8983449
TI  - [A case of respiratory tract hemorrhage during a course of pulmonary tuberculosis
      recognized during surgery].
AB  - A 28-years old woman was admitted to the Cardio-thoraco-surgical ward because of
      massive hemoptysis without any clinical complaints. Mycobacteria were not found
      in sputum smear. The FOB and radiological findings suggested a bleeding from the
      6-th segment of the left lung. In resected segment the necrotic lesions,
      suggesting tuberculosis were found. After 4 weeks positive results of specimen
      culture were confirmed. She received antituberculous treatment.

PMID- 8983450
TI  - [Chronic semi-invasive aspergillosis with broncho-pleural fistula treated with
      itraconazole and surgically].
AB  - A case of 25 years lasting semi-invasive (necrotic) aspergillosis is presented.
      Aspergilloma in the probably post-tuberculous cavity was the first sign of the
      disease. Then, in the course of disease, two broncho-pleural fistulas,
      bronchiectases and cirrhosis of the lung were observed. Effective antifungal
      treatment with itraconazole was followed by pneumonectomy of the affected lung.

PMID- 8983451
TI  - [A case of Morgagni's hernia treated surgically].
AB  - The case of a patient operated upon for Morgagni's hernia, diagnosed through
      radiological examination and confirmed by a CT examination of the thorax is
      presented. Right thoracotomy was performed and Morgagni's hernia containing
      preperitoneal fatty tissue was found. Corrective plastic was carried out with
      good result.

PMID- 8983452
TI  - [Clinical manifestations, diagnosis and treatment of exercise induced asthma].

PMID- 8983453
TI  - [Pathomechanism of exercise induced bronchospasm].

PMID- 8983454
TI  - [Major feline allergen--Fel d I immunologic-biochemical aspects].

PMID- 8983455
TI  - [Major feline antigen--Fel d I clinical aspects].

PMID- 8983456
TI  - [Cystic fibrosis--prevention, diagnosis, treatment].

PMID- 8983457
TI  - [Composition, secretion and function of pulmonary surfactant].

PMID- 8983458
TI  - Orthopaedic physical therapy: do we have a research vision?

PMID- 8983459
TI  - Harry Zimmerman, M.D.

PMID- 8983460
TI  - Epidemiological appraisal of studies of residential exposure to power frequency
      magnetic fields and adult cancers.
AB  - OBJECTIVES: To appraise epidemiological evidence of the purported association
      between residential exposure to power frequency magnetic fields and adult
      cancers. METHODS: Literature review and epidemiological evaluation. RESULTS:
      Seven epidemiological studies have been conducted on the risk of cancer among
      adults in relation to residential exposure to power frequency magnetic fields.
      Leukaemia was positively associated with magnetic fields in three case-control
      studies. The other two case-control studies and two cohort studies did not show
      such a link. Brain tumours and breast cancer have rarely been examined by these
      studies. Based on the epidemiological results, the analysis of the role of chance
      and bias, and the criteria for causal inferences, it seems that the evidence is
      not strong enough to support the putative causal relation between residential
      exposure to magnetic fields and adult leukaemia, brain tumours, or breast cancer.
      Inadequate statistical power is far more a concern than selection bias,
      information bias, and confounding in interpreting the results from these studies,
      and in explaining inconsistencies between studies. CONCLUSIONS: Our reviews
      suggested that the only way to answer whether residential exposure to magnetic
      fields is capable of increasing the risks of adult cancers is to conduct more
      studies carefully avoiding methodological flaws, in particular small sample size.
      We also suggested that the risk of female breast cancer should be the object of
      additional investigations, and that future studies should attempt to include
      information on exposure to magnetic fields from workplaces as well as residential
      exposure to estimate the effects of overall exposure to magnetic fields.

PMID- 8983461
TI  - Identifying environmental risk to male reproductive function by occupational
      sperm studies: logistics and design options.
AB  - Malfunction of the male reproductive system might be a sensitive marker of
      environmental hazards, the effects of which may extend beyond reproductive
      function. The testis is more vulnerable to heat and ionising radiation than any
      other organ of the body and several xenobiotics are known to disrupt
      spermatogenesis after low level exposure. Studies of environmental impact on
      human health are often most informative and accurate when carried out in the
      workplace where exposures can be high and easy to document. Semen analysis
      provides readily obtainable information on testicular function. The main
      advantages in comparison with functional measures such as fertility rates and
      time taken to conceive are the possibilities to examine men independently of
      marriage and pregnancy, to find changes of fecundity with different exposures
      within the same person and to detect adverse effects when no alteration of
      fertility is yet taking place. In the implementation of an occupational sperm
      study considerable attention must be paid to logistic issues. A mobile laboratory
      unit for initial semen preparation and processing may in some situations increase
      worker compliance and the quality of sperm cell motility. The cross sectional
      design which has been used in almost all male reproductive studies so far has
      several severe limitations including selection bias because of differential
      participation, difficulties in defining a suitable reference group, and lack of
      information about the time dimension of the cause-effect relation. The
      longitudinal design deals adequately with most of these constraints. Semen
      samples are collected before, during, and possibly after exposure to the risk
      factor of interest and causal inferences are based upon change of semen variables
      within a man over time rather than upon differences between men. The logistics of
      the longitudinal study may benefit from pre-employment health examinations to
      enrol newly hired workers and require fewer participants to obtain comparable
      statistical power. In conclusion, andrological methods and epidemiological
      designs are available for the implementation of valid studies concerned with
      environmental impact on human testicular function. Occupational sperm studies
      should probably not be the first choice when the objective is initial screening
      of environmental impact on fertility but should be implemented when their is a
      need to corroborate or refuse earlier evidence that specific exposures have
      impact on testicular function.

PMID- 8983462
TI  - Abnormalities on neurological examination among sheep farmers exposed to
      organophosphorous pesticides.
AB  - OBJECTIVES: Organophosphates are effective pesticides which are frequently used
      in several agricultural settings. Although their acute effects are well
      characterised, it remains unclear whether long term exposure can damage the human
      nervous system. This study sought to investigate their long term effects by
      comparing abnormalities on neurological examination between groups of workers
      exposed to organophosphates and an unexposed group. METHODS: 146 exposed sheep
      farmers and 143 unexposed quarry workers were recruited into a cross sectional
      study of symptoms and neuropsychological effects of long term exposure to
      organophosphates in sheep dip. From a symptom questionnaire given immediately
      after dipping the 10 most symptomatic and 10 least symptomatic farmers were
      selected. Several months later each of these, along with 10 of the unexposed
      quarry workers, underwent a standardised neurological examination similar to that
      which might be used in clinical practice, at at time as remote as possible from
      recent exposure to organophosphates so as to exclude any acute effects. RESULTS:
      All 30 selected subjects agreed to participate. The components of the examination
      which showed a significant difference were two point discrimination on the dorsum
      of the hand (symptomatic farmers 22 mm; asymptomatic farmers 13 mm; quarry
      workers 8 mm) and the dorsum of the foot (symptomatic farmers 34 mm; asymptomatic
      farmers 10 mm; quarry workers 11 mm), and mean calf circumference (symptomatic
      farmers 35.0 cm; asymptomatic farmers 36.3 cm; quarry workers 38.6 cm). Overall
      the prevalence of neurological abnormalities was low. CONCLUSIONS: The
      differences in neurological examination detected between groups were subtle and
      their clinical significance was unclear. However, they do suggest evidence of an
      adverse neurological effect from exposure to organophosphates. Further, larger
      scale studies will be required before it is possible to confirm or refute the
      differences detected.

PMID- 8983463
TI  - Glioma and occupational exposure in Sweden, a case-control study.
AB  - OBJECTIVES: The aim of the study was to analyse whether any job titles,
      industrial codes, and certain occupational exposures were associated with an
      increased risk of glioma. METHODS: A population based case-control study of
      incident primary brain tumours in adults was carried out in Uppsala, Sweden in
      the period 1987-90. The study included 192 cases of glioma and 192 matched
      controls. It also included cases with other tumours of the central nervous system
      with matched controls. Information from all 343 controls was used in this study.
      Information was collected by means of a questionnaire that was sent to all
      subjects. An occupational hygienist reviewed the questionnaires for self reported
      exposures to substances and assessed whether these reported exposures were
      plausible or not in the corresponding occupation. RESULTS: The kappa coefficient
      for those classified by the two methods ranged between 0.46 and 0.88, and they
      were almost the same for cases and controls. For men exposed to solvents a
      relative risk (RR) of 2.6 (95% CI 1.3 to 5.2) was found. For men exposed to
      pesticides the RR was 1.8 (95% CI 0.6 to 5.1), and for plastic materials the RR
      was 3.6 (95% CI 1.0 to 12.4). For men employed in forestry and logging the RR was
      2.2 (95% CI 0.9 to 5.3) and in basic metal industries 2.0 (95% CI 1.0 to 4.0).
      CONCLUSION: An increased risk of glioma was associated with use of solvents,
      pesticides, and plastic materials but this should be interpreted with some
      caution.

PMID- 8983464
TI  - Hairy cell leukaemia and occupational exposure to benzene.
AB  - OBJECTIVES: The role of occupational exposures in hairy cell leukaemia (HCL) was
      investigated through a multicentre, hospital based, case-control study. This
      paper analyses the role of exposure to benzene in HCL. METHODS: A population of
      226 male cases of HCL and 425 matched controls were included in the study.
      Benzene exposure was evaluated by expert review of the detailed data on
      occupational exposures generated by case-control interviews. RESULTS: No
      association was found between HCL and employment in a job exposed to benzene
      (odds ratio (OR) 0.9 (95% confidence interval (95% CI) 0.6-1.3)). The sample
      included 125 subjects, 34 cases (15%), and 91 controls (21%) who had been exposed
      to benzene, as individually assessed by the experts, for at least one hour a
      month during one of their jobs. Benzene exposure was not associated with a risk
      of HCL (OR 0.8 (0.5-1.2)). No trend towards an increase in OR was detected for
      increasing exposures, the percentage of work time involving exposure to > 1 ppm,
      or the duration of exposure. No findings suggested a particular risk period, when
      the OR associated with the time since first or last exposure, or since the end of
      exposure, were examined. CONCLUSIONS: In conclusion, with the low exposures
      prevalent in the sample, the study did not show any association between benzene
      exposure and HCL.

PMID- 8983465
TI  - A study of mortality among 14,730 male workers in 12 Norwegian ferroalloy plants:
      cohort characteristics and the main causes of death.
AB  - OBJECTIVES: Concern about the health hazards of exposure to workers in the
      ferroalloy industry has initiated this historical cohort study. The aim was to
      examine the mortality pattern among male employees in 12 Norwegian ferroalloy
      plants. METHODS: All men employed for at least six months who started their first
      employment during 1933-91 were eligible for the cohort. Deaths observed during
      1962-90 were compared with expected figures calculated from national mortalities.
      Internal comparisons of rates were performed by Poisson regression analysis. The
      final cohort comprised 14,730 male employees who were observed for 288,886 person
      years. RESULTS: Mortality from all causes of death was slightly increased (3390
      deaths, standardised mortality ratio (SMR) 1.08, 95% confidence interval (95% CI)
      1.04-1.11). Regression analysis of total mortality showed a significant negative
      trend for the rate ratios with increasing duration of employment. An increased
      mortality was found among employees in urban plants compared with employees in
      rural plants (rate ratio (RR) 1.21, 95% CI 1.13-1.29). Excess deaths from cancer
      (SMR 1.11) and sudden death (SMR 1.47) were found among employees with at least
      three years of employment. Mortality from accidents, poisonings, and violence was
      increased among all employees (SMR 1.28). Excess deaths from this cause were
      however only found for the time after the end of employment in this industry and
      not during employment (SMR 0.90). CONCLUSIONS: The increased mortality from
      cancer and sudden death could be related to work exposures, at least in
      subgroups, and these results warrant further studies. The excess deaths from
      accidents, poisonings, and violence were probably not related to work exposures.
      The mortality results for short term workers and other information indicate that
      systematic errors contribute to the increased overall mortality.

PMID- 8983467
TI  - Carinal and tubular airway particle concentrations in the large airways of non
      smokers in the general population: evidence for high particle concentration at
      airway carinas.
AB  - OBJECTIVE: To evaluate the extent to which human airway carinas accumulate
      ambient atmospheric particles, a newly developed technique was used to micro
      dissect and analyse particle concentration in tubular segments and carinas of the
      large airways of 10 necropsy lungs from non-smokers from the general population
      of Vancouver. METHODS: Ratios of the particle concentrations on the carinas to
      the tubular segment immediately preceding it were measured with analytical
      electron microscopy for the mainstem bronchus, upper and lower lobe bronchi, and
      four different segmental or subsegmental bronchi--that is, Weibel generations 1
      to about 5. A total of 119 carinal-tubular pairs was evaluated. RESULTS: Over all
      cases, both carinal and tubular particle concentrations increased with increasing
      airway generation; the median ratio of carinal to tubular particle concentration
      was 9:1 and did not show any trend with airway generation. The ratio was > 5 in
      71% of carinal-tubular pairs, > 10 in 42% of pairs, > 20 in 31% of pairs, and >
      100 in 9% of pairs. Some subjects showed a notable tendency to high ratios, with
      many ratios > 100, and other subjects had a tendency toward low ratios. The
      predominant mineral species in both carinas and tubular airway segments was
      crystalline silica and the relative proportion was similar in both sites;
      however, mean particle diameter was consistently less in the carinal tissues.
      CONCLUSIONS: These findings suggest that the ratio of carinal to tubular retained
      particles in the large airways in non-smokers is higher than might be supposed
      from data generated in airway casts, and that there is considerable variation in
      this ratio between subjects. This finding is of potential interest in models of
      carcinogen, toxin, and dose of fibrogenic agent to the large airways as it
      suggests high and sometimes extreme concentrations of toxic particles at carinas,
      and thus reinforces the notion that carinas may be sites of initiation of
      disease.

PMID- 8983466
TI  - Mesothelioma in a community in the north of England.
AB  - OBJECTIVES: To find the numbers of mesotheliomas in Calderdale over the period
      1966-94 and determine their relation to asbestos exposure, pathology, and mineral
      fibre burden within the lungs of affected subjects. METHODS: Cases were entered
      into the study if the subject has been diagnosed with mesothelioma after
      postmortem and histopathological examinations. Occupational data were obtained
      mainly from the case records of the Cape Asbestos medical officer, hospital, and
      medical practitioner and from death certificates. Analyses of the mineral fibres
      were performed with transmission electron microscopy and energy dispersive x ray
      spectrometry. RESULTS: 73 mesotheliomas were diagnosed from 1966 to 1994. Forty
      four were associated with exposure at the Acre Mill factory, which manufactured
      asbestos products. Concentrations of amphibole asbestos fibres were found to be
      raised above controls in 31 out of 32 cases associated with Acre Mill exposure,
      in 10 out of 12 other cases exposed to asbestos and eight out of 17 cases not
      exposed to asbestos. CONCLUSIONS: There was a high number of mesotheliomas in
      Calderdale. More than half of the cases were associated with occupation at the
      Acre Mill factory and were associated with exposure to amphibole asbestos,
      predominantly crocidolite. No cases associated with neighbourhood exposure to
      asbestos were identified.

PMID- 8983468
TI  - Comparison of dust related respiratory effects in Dutch and Canadian grain
      handling industries: a pooled analysis.
AB  - OBJECTIVES: Four previously conducted epidemiological studies in more than 1200
      grain workers were used to compare exposure-response relations between exposure
      to grain dust and respiratory health. METHODS: The studies included Dutch workers
      from an animal feed mill and a transfer grain elevator and Canadian workers from
      a terminal grain elevator and the docks. Relations between forced expiratory
      volume in one second (FEV1) and exposure were analysed with multiple regression
      analysis corrected for smoking, age, and height. Exposure variables examined
      included cumulative and current dust exposure and the numbers of years a subject
      was employed in the industry. Sampling efficiencies of the Dutch and Canadian
      measurement techniques were compared in a pilot study. Results of this study were
      used to correct slopes of exposure-response relations for differences in dust
      fractions sampled by Dutch and Canadian personal dust samplers. RESULTS: Negative
      exposure-response relations were shown for regressions of FEV1 on cumulative and
      current exposure and years employed. Slopes of the exposure-response relations
      differed by a factor of three to five between industries, apart from results for
      cumulative exposure. Here the variation in slopes differed by a factor of 100,
      from -1 to -0.009 ml/mg.y/m3. The variation in slopes between industries reduced
      to between twofold to fivefold when the Dutch transfer elevator workers were not
      considered. There was evidence that the small exposure-response slope found for
      this group is caused by misclassification of exposure and a strong healthy worker
      effect. Alternative, but less likely explanations for the variation in slopes
      were differences in exposure concentrations, composition of grain dust, exposure
      characteristics, and measurement techniques. CONCLUSION: In conclusion, this
      study showed moderately similar negative exposure-response relations for four
      different populations from different countries, despite differences in methods of
      exposure assessment and exposure estimation.

PMID- 8983469
TI  - Relation between pulmonary clearance and particle burden: a Michaelis-Menten-like
      kinetic model.
AB  - OBJECTIVES: To test the validity of a Michaelis-Menten-like kinetic model of
      pulmonary clearance of insoluble dusts. METHODS: Data were investigated from
      studies of pulmonary clearance in F344 rats exposed to antimony trioxide (Sb2O3),
      photocopy test toner, polyvinyl chloride powder (PVC), and diesel exhaust
      particles. The Michaelis-Menten-like model was used to develop a relation in
      which the pulmonary clearance half time was a linear function of lung burden.
      After combining all data, linear regression techniques were applied to
      investigate the underlying relations. With the estimated intercepts and slopes,
      the Michaelis-Menten-like kinetic parameters kmax (maximal clearance rate) and
      m1/2 (a characteristic lung burden at which kmax is reduced by 50%) were derived
      for the four dusts. RESULTS: The experimental data fit the linear regression very
      well (R2 = 0.989), suggesting that pulmonary clearance for the four dusts
      followed Michaelis-Menten-like kinetics. Values of the intercept terms were not
      significantly different among the four dusts (P = 0.294), indicating that the
      intrinsic clearance rates of F344 rats were the same among the four experiments.
      The intrinsic clearance half time was estimated to be 77.8 days, leading to an
      estimated kmax of 0.0089 day-1. However, the slopes of the linear relations were
      significantly different among the four dusts (P < 0.001). Values of m1/2 were
      ranked in the order of: Sb2O3 (0.69 mg) < photocopy test toner (0.97 mg) < diesel
      exhaust (2.49 mg) congruent to PVC (2.90 mg). CONCLUSION: This study suggests
      that the Michaelis-Menten-like kinetic model reasonably describes the kinetic
      behavior of pulmonary clearance in F344 rats. The parameters m1/2 can be used to
      differentiate the potency of a particular dust for impairing pulmonary clearance.

PMID- 8983470
TI  - Laboratory animal allergy: anaphylaxis from a needle injury.
AB  - A 32 year old male research physician accidentally received a minor wound from a
      needle which had been previously used on rabbit tissue. Within 15 minutes serious
      anaphylactic reactions started and he was taken to hospital where his condition
      stabilised within five hours. Serum immunoglobulin E antibodies to rabbit
      epithelium were high (16.2 U/ml), although other antibody titres were low.
      Allergy tests were not carried out before employment, so this alarming scenario
      could not have been predicted. People with confirmed laboratory animal allergy
      should be warned of the dangers of continued unprotected exposure and avoidance
      of the allergen should be encouraged by good laboratory practice and respiratory
      protective equipment.

PMID- 8983471
TI  - Risk of thyroid nodules in subjects occupationally exposed to radiation: a cross
      sectional study.

PMID- 8983472
TI  - A cross sectional study of the independent effect of occupation on lung function
      in British coal miners.

PMID- 8983473
TI  - [Treatment of neonatal thrombocytopenia].
AB  - Treatment of neonatal thrombocytopenia is dependent on its etiology and severity.
      The best indication for treatment with immunoglobulins is autoimmune
      thrombocytopenia. Platelet and blood transfusions are justified mainly in the
      presence of severe infection. The only indication for platelet transfusion is
      severe thrombocytopenia (platelet count below 30 G/L).

PMID- 8983474
TI  - [The ultrastructural reorganizations in the formations of the rat endbrain in
      decreased motor activity not evoking stress].
AB  - Ultrastructure of central and lateral nuclei of amygdala, singular gyrus and
      caudal nucleus was studied in rats subjected to non-stress 90-days-long
      hypokinesia. Not numerous changes basically reflecting decrease of activity of a
      series of neurons and synapses were noted in all the formations. Selective nature
      of the action was demonstrated: in every region examined mostly one certain cell
      type changes. The data were compared with the results of earlier performed
      research concerning the action of "hypokinetic stress" on the same brain
      formations.

PMID- 8983475
TI  - [Morphological changes in the rat brain after applying electrostimulation to the
      emotiogenic areas of the lateral hypothalamus].
AB  - Celloidin slices of brain were studied histologically by means of Nissl method in
      Wistar line rats 3 and 8 months after kindling formation initiated by
      electrostimulation of the lateral hypothalamus emotiogenic zones. part of brain
      neurons appeared to acquire destructive changes, grow dark and wrinkle, while
      some of them died. A great number of such neurons were found in the nuclei of
      base brain, thalamus, hypothalamus and pons varolii with hemorrhages seen in
      different brain zones. Besides, 8 months after the kindling formation, large
      spherical bodies painted metachromatically by toluidin blue were found in white
      substance of many brain zones. These bodies are likely the product of generation
      and metabolic disorders in myelinated fibres. The data obtained indicate that
      kindling initiated by hyperexcitation of emotiogenic brain systems results in
      organic brain disease similar to that in epilepsy.

PMID- 8983476
TI  - [Projections of the amygdaloid body and dopaminergic mesencephalic formations to
      the entopeduncular nucleus of the cat brain].
AB  - Organization of projections on entopeduncular nucleus different regions from
      amygdala and from nuclei of tegmental ventral field and black substance was
      studied in cat using retrograde axonal transport of house radish peroxidose.
      Analysis of the labelled neurons distribution in these structures in separate
      marker injections into the rostral and caudal segments of entopeduncular nucleus
      allowed to conclude that projective fibres to rostral region come from not
      numerous neurons of tegmental ventral field and black substance compact part, and
      to caudal one apart from these structures neurons--also from scanty neurons of
      dorsal and lateral parts of black substance. Projections on entopeduncular
      nucleus from amygdala were not found.

PMID- 8983477
TI  - [Ultrastructural changes in the encapsulated nerve endings of the tibial nerve
      under the action of diethyl ether in 2 strains of rats selected for their
      threshold of nervous system excitability].
AB  - Ultrastructure of tibial nerve receptor endings was studied in two rat lines
      different in the threshold of the nerve excitation after decapitation and
      euthanasia with diethyl ether use. Interlinear diversities of shape and
      parameters of receptor endings and their mitochondria were established. The
      results obtained indicate different reactivity of rats varying in genetically
      determined nervous system excitation threshold to tissue respiration decrease and
      oxygen insufficiency on ultramicroscopic levels.

PMID- 8983478
TI  - [The structural organization of the neurocytes of the nodose ganglion of the
      vagus nerve that innervate different digestive tract organs in rats].
AB  - Introduction of conjugated horse radish peroxidase and wheat germ agglutinin into
      different digestive tract organs of the rat and following computer analysis of
      the sensitive neurocytes morphometric characteristics allowed to establish the
      signs of morphological specialization for the populations of the vagus caudal
      notes sensitive neurocytes, involved in different organs innervation. Neurocytes,
      innervating certain organs were found to vary significantly in shape parameters
      and metric characteristics.

PMID- 8983479
TI  - [The participation of mast cells and serotonin-immunoreactive fibers in the
      innervation of the cerebral vessels].
AB  - Interrelations between adrenergic and serotoninergic nerve fibres and mast cells
      located near the vascular wall were studied on total preparations of rat brain
      pia mater. Histochemical method with glyoxylic acid revealed the dense network of
      adrenergic fibres and their terminal regions with variceal endings with mast
      cells located next to them. Immunohistochemical methods (fluorescent and method
      with use of peroxidase antiperoxidase complex) with the aid of antiserum
      serotonin showed the content of serotonin in these cells. Distribution of
      serotoninergic nerve fibres resemble that of adrenergic fibres with density being
      significantly lower. The fibres have frequent contacts with mast cells processes.
      These data indicate the presence of functional connection between serotonin
      positive nerve fibres and the possibility of their drawings in control of blood
      circulation of brain.

PMID- 8983481
TI  - [Structural changes in the walls of the intraorganic vessels of the kidney in
      experimental aortic coarctation].
AB  - Structural changes of renal arteries and glomeruli were studied in 25 dogs with
      hemodynamic model of coarctation of the aorta in different terms of experiment by
      of histochemical, histoenzymological and morphometric methods also using 10
      control animals. Dystrophic processes were established to develop in media of
      renal arteries and myocytes within the first week of the disease induction. In
      later stages of the experiment a number of adaptive, compensatory and
      pathobiological changes associated with the decrease of renal basin blood supply
      appear in renal vessels. First lie in atrophia of the muscular coat circular
      layer in renal arteries and arterioles, second--in reorganization of part of them
      and third--in sclerosis and hyalinosis of arteriolar branches and glomeruli.

PMID- 8983480
TI  - [The biomicroscopic evaluation of the blood microcirculatory bed in the mesentery
      of the small intestine during experimental perftoran infusion under
      normovolemia].
AB  - Dynamics of biomicroscopic state of hemomicrocirculatory bed (HMCB) of small
      intestinal mesentery was studied in go both sexes albino outbred rats in
      conditions of intravenous administration of 1.0 ml perfuoram (PF) with
      simultaneous control of the experiment by intravenous isotonic solution
      administration. Biomicroscopy was performed 30 minutes, 3, 6 and 24 hours later.
      30 minutes after the PF administration bloodflow reduction in afferent vessels,
      elongation of construction period of resistant vessels and 18% decrease of
      vessels were demonstrated. Precapillary diameter decreased on 23% with respect to
      control with isotonic solution. Tortuosity of precapillaries and decrease of
      functioning capillaries number. 3 hours after the PF infusion blood flow turned
      more slow, signs of adhesion between leukocytes and postcapillary venules lumenal
      surface appeared and perivascular infiltrate had formed. Diameter of alducent
      vessels reduced in comparison with control and went lugher against the 30-minutes
      research stage. On the whole bloodflow in resistant vessels turns homogeneous. 6
      hours after PF infusion homogeneous bloodflow could be seen. Number of arteriolar
      vasomotions grew up to control and made 14 in a minute. Venular diameter was
      close to control. Biomicroscopy of HMCB 24 hours after infusion did not reveal
      essential differences compared to with isotonic solution administered.

PMID- 8983482
TI  - [The classification of variants and anomalies of the human skull].
AB  - The classification suggested represents an attempt to unite embryological,
      topographical, and morphological approaches aimed to achieve a more complete
      review both of abnormalities and anatomical variants of cranium. 9 teratological
      groups are distinguished in it.

PMID- 8983483
TI  - [The size and shape of the orbits and their correlation with the size and shape
      of the cerebral and visceral portions of the cranium].

PMID- 8983484
TI  - [Age-related changes in the intervertebral disks based on magnetic resonance
      tomographic data].
AB  - Lumber region of vertebral column was studied in different age people using
      magnetic resonance tomography (MRF). Intensity of vertebral discs signals and
      those from adjacent vertebral bodies was evaluated both visually and
      quantitatively by graphic registration of magnetic resonance signals. Processes
      of disk dehydration, characteristic for age changes were detected spontaneously
      as the signal intensity grows smaller. It was established that magnetic resonance
      signals of maximal intensity come from pulposus nucleus in juvenile age. This
      intensity significantly exceeds that from the adjacent disks. On the initial
      stage of dehydration "doubling" of the MR signal may be observed so as decrease
      of the intensity up to the level of signals from the adjacent disks. This method
      suggested allows to assess early stages of the disk dehydration and to determine
      age norms.

PMID- 8983486
TI  - [The structural and metabolic characteristics of bronchial smooth myocytes in
      thanatogenesis].
AB  - The present research was aimed to study the dynamics of changes of bronchial
      smooth myocytes morphometric and cytospectrophotometric indexes in
      thanatogenesis. Selected dissociation of albino outbred rat bronchial smooth
      myocytes was performed right after animals were killed (3, 6, 12, 24 and 48 hrs).
      Smears of the dissociated myocytes, stained after Feulgen to be revealed on DNA
      and of amid black stained general protein were examined by scanning
      cytospectrophotometer. Morphometric parameters of nucleus and cytoplasm were
      determined simultaneously. Continuous decrease of optical density of summary
      protein and DNA, corresponding with data from literature was found. Volume of
      myocyte cytoplasm significantly grows smaller within first 12 postmortem hrs,
      which results from population structure alteration due to elimination of cells
      with basically large cytoplasmic volume. Thus not only dynamics of cytochemical
      and linear parameters changes in cells should be taken into consideration in
      postmortem histological analysis of the lung material but also the changes of
      cell population structure.

PMID- 8983485
TI  - [The morphofunctional status of the synovial membrane of the temporomandibular
      joint under exposure to a helium-neon laser].
AB  - By means of light and electronic microscopy the state of tissues of the
      temporomandibular joint synovial coat was examined in dogs. As a results a model
      of aseptic inflammation of temporomandibular joint was created (the first series
      of experiments), the impact of different dozes of helioneonic laser on intact
      tissues was studied and the most efficient doze of irradiation was established
      (the second series of experiments). On the third series it was shown that the
      doze of irradiation chosen influences positively the structural changes in
      synovial coat, caused by the aseptic inflammation.

PMID- 8983488
TI  - [The cytoarchitectonic characteristics of the frontal fields of the brain in
      gifted people].
AB  - Frontal area fields 8 and 47 were studied in gifted people of different age using
      series of frontal paraffin slices. Neuronal parameters were detected. Density of
      localization was determined in neurons and gliocytes including perineuronal ones
      and also in lipofuscin, containing neurons and those surrounded with satellite
      gliocytes. Relation of the latter to general number of pyramidal neurons in
      layers 3 and 5 of cortical fields (index HC/C) was defined so as the thickness of
      cortex and its certain layers. Brain of the same age common people served as the
      control. The sum total of characters determined (both general and individual) and
      especially the neuroglial system state (more than double increase against the
      control with HC/H index) exceeds both age and individual variability and is
      probably typical for the frontal area of exceptionally gifted people and is not
      dependent on age and type of brightness.

PMID- 8983487
TI  - [Ultrastructural changes in the interstitial cells of the kidney medullary
      substance in suckling rabbits with experimental cholera].
AB  - A culture of virulent selection of cholera vibrios L-top 5879 was introduced
      through the probe to suckling rabbits-pups 10 to 12 days old. Ultrastructural
      changes of interstitial cells and capillaries of kidney medulla were studied.
      During vibrio adhesion (4 hrs after the inaction) interstitial cells acquire
      dystrophic changes, lipid granules content reduces, while vascular permeability
      grows higher which suggests the presence of prostaglandin precursors elimination
      into blood flow. Cholera development (1-2 days later) is accompanied with
      progressing of signs of prostaglandin synthesis activation and their precursors
      passage into the vascular bed.

PMID- 8983489
TI  - [The dynamic cytochemical properties of the protective barrier of the stomach
      during dalargin administration].
AB  - Dalargin influence on secretory elements of the stomach protective barrier was
      studied. Dynamics of the stomach barrier histochemical properties dependent on
      the term of dalargin introduction (1-11 days) was demonstrated. General effect of
      dalargin displays in alteration of glycoprotein synthesis speed by fundal glands
      and tegmental epitheliocytes and for mucocytes its influence may be followed up
      in changes of chemical composition of glycoproteins secreted by them.

PMID- 8983490
TI  - [The determination of NADPH-diaphorase activity in the rat brain after fixation
      for different lengths of time].

PMID- 8983491
TI  - [Physicochemical dissociation methods in the preparation of biological objects
      for scanning electron microscopy].

PMID- 8983492
TI  - [Anatomico-echocardiographic studies of the fetal and neonatal heart].

PMID- 8983493
TI  - [Founded by Lesgaft (on the centenary of the Department of Anatomy and Sports
      Morphology of the P. F. Lesgaft Academy of Physical Education)].

PMID- 8983494
TI  - [The phenomenon of focal sympathetic denervation of the major vessels in the
      development of atherosclerosis].
AB  - 22 aortas obtained from people aged 20-55 who died in accidents by early
      dissections were studied. Adrenergic nerve plexuses of aortal wall were examined
      by quantitative neurohistochemical method. Focal reduction of indexes of these
      plexuses density was defined by the age of 30. The process of desympathization
      runs unevenly with nerve plexuses from zones of aorta cranial to areas of its
      branching altered to greater extent. This very zones are subjected to
      atherosclerosis selectively. We tend to consider the process of desympathization
      for one of atherosclerosis factors developing in vascular wall zones with the
      loss of adaptive-trophic influence of the vegetative nervous system sympathetic
      activity.

PMID- 8983496
TI  - [The effect of vagotomy on neuronal function in different sections of the
      autonomic nervous system].
AB  - Neuronal structure was studied during a year after the truncal subdiaphragmatic
      two-side vagotomy in nuclei of vagal nerves and oblongated medulla. Jacobson
      nuclei in the spinal cord lateral cornua and stomach and intestinal nerve
      plexuses. Dynamics of structural changes in nervous system different regions
      after vagotomy was shown. In intramural nerve ganglionic structure repairs on
      late post operative terms, while vagal nerve nuclei in the oblongated medulla
      retain significant changes, one of which is the sharp decrease of neuron number a
      year after vagotomy. Compensation of Jacobson nuclei similar to nucl.
      intermediolateralis was taken into consideration. So vagotomy is a surgical
      intervention into nervous system and into endocrine system associated with it.

PMID- 8983495
TI  - [The effect of chemical sympathectomy on the adrenergic innervation of the blood
      vessels belonging to different organs in salt-sensitive and salt-resistant Dahl
      strain rats].
AB  - The action of chemical desympathization by 6-hydroxydophamine influencing
      adrenergic innervation in different organs vessels (mesenterial, renal and
      femoral) was studied using histochemical fluorescent method in salt susceptible
      and salt-resistant Dahl rats kept on a low- and high-salt diet. Heterogeneity of
      adrenergic innervation of different region vessels was established to display and
      6-hydroxydophamine caused complete desympathization only in mesenterial artery
      and in all veins, while in renal artery retained adrenergic plexus its certain
      branching and femoral artery-in two thirds of its surface. The process of
      reinnervation in vessels running with different intensity in different animals
      and in different vessels was found to start in vessels of majority of animals on
      day 5-6 after the chemical desympathization. 6-hydroxydophamine had greater
      impact on the vessels of salt-susceptible high salt rat (hypertension) and salt
      resistant high-salt-diet (normension) rats. Thus, the state of arterial and
      venous adrenergic apparatus in hypertension Dahl rats is determined not by the
      increased blood pressure itself but by the natrium metabolism disturbance.

PMID- 8983498
TI  - [The detection of the horizontal afferent connections of one orientation column
      in the cat visual cortex].

PMID- 8983497
TI  - [The effect of nerve growth factor on regeneration of the fibers in the rat
      sciatic nerve].
AB  - Exogenic nerve growth factor in the crushed nerve of rat promotes the development
      of reparative-regenerative processes. This was established by electron microscopy
      and electrophysiological method and is expressed through the activation of
      phagocytosis in the remained crushed axons in distal segments, relatively more
      early and vast penetration of the growing fibres to the outside of the traumatic
      zone, a single supramaximum stimulation of proximal region above the appearance
      and growth of action potential amplitude and also its spreading to the periphery
      as compared to control animals, treated with equal amounts of isotonic natrium
      chloride.

PMID- 8983499
TI  - [Neurovasal relations in the human neocortex].
AB  - Different types of interneurons producing nitric oxide in human brain motor
      cortex were studied by means of histochemical reaction to NADPH diaphorase--the
      marker of nitric oxide synthase. Non-synaptic dendrito-, axo- and somatovasal
      contacts between typical smooth and spinous checking interneurons were shown. A
      hypothetic scheme of local blood circulation control is represented, after which
      these cells, exerting inhibitory synaptic action on pyramidal neuron at the same
      time cause vasodilatation by secreting nitric oxide near to the capillary.
      Scientific Research laboratory of Biological Mechanisms of Structural Maintenance
      of Homeostasis, Russian Medical University, Moscow.

PMID- 8983501
TI  - [Perforated synapses of the neocortex and their role in the reorganization of the
      interneuronal relations in the postischemic period (a morphometric study)].
AB  - The influence of sudden systemic hemostasis on the change dynamics of numerical
      density of perforated (PS) and non-perforated (NS) interneuronal synaptic
      contacts in cerebral sensomotor cortex layer 1 were studied in albino rats during
      30 postischemic days using electron microscopy and morphometric methods of
      examining the material treated with osmium and contrasted with phosphotungstic
      acid. Regularities of junction and disjunction mechanisms realization in arising
      PS from NS in diverse postischemic terms were demonstrated. A significant role of
      PS appearance in reorganization of neocortical neuronal interrelations is shown.

PMID- 8983500
TI  - [Serotonin-reactive neurons of the neocortex].
AB  - In the course of study performed on Wistar line rats using light and electron
      microscopy it was found that brain serotoninergic system damage by the selective
      neurotoxin of 5,7 dihydroxytryptamine leads to degenerative changes in certain
      pyramidal neurons of the motor cortex superficial layers. Deep layers pyramid
      neurons acquire the signs of functional activity increase with the appearance of
      intranuclear inclusions. The results obtained are discussed with taking to
      consideration the impact of serotoninergic system damage on the neuropsychic
      diseases pathogenesis.

PMID- 8983502
TI  - [The significance of the vascularization of embryonic donor brain for the
      viability of intraocular transplants in the rat].
AB  - Telencephalic regions of rat embryonic brain were transplanted into the adult rat
      eye anterior chamber on E12 and E14 stages of development. These stages fall on
      the onset of the vascularization and the presence of the well developed vascular
      network in the embryonic brain. After a month of cultivation E14 transplants were
      much more viable than E12 (appropriately 58% and 15%). Only few E12 grafts had no
      initial vascularization. These transplants displayed growth retardation, while
      differentiated neurons could be seen only on their periphery. The results of the
      investigation demonstrate the meaning of vascularization extent in donor
      embryonic nervous tissue in its survival in conditions of transplantation into
      the rat eye anterior chamber.

PMID- 8983503
TI  - [Rosette formation in explants of human embryonic neocortex (an electron
      microscopic study)].
AB  - Multiple invaginations and closed cavities (rosettes) were developed in 199
      fragments of wall of human anterior cerebral vesicle. Contraction of
      neuroepithelial cells apexes after the principle of the gathered tobacco pouch
      was involved into the process. This confirms the previous suggestion of the
      authors on the similarity between the mechanisms of rosettes forming and
      neurulation. The participation of radial glia cells and neuroblasts in the
      reorganization of the neocortex germ was also studied.

PMID- 8983504
TI  - [The ultrastructure of the neuronal subpopulations of the paraventricular
      hypothalamic nuclei in stress and the stress-limiting action of a pulsed
      electrical current].
AB  - Neurons of medial microcellular and posterior macrocellular subnuclei of
      hypothalamus, producing stress-releasing hormones (CRF and V), acting together in
      initiation and regulation of the organism stress reactions were studied.
      Ultrastructural analysis and automatized data could reveal decrease of secretory
      vesicles number and enlightenment of neurosecretory granules content in
      immobilization, which indicates active hormone elimination from neuron bodies.
      Characters of the disturbing stressor effect on different organelles, mainly on
      endoplasmic reticulum were found. Transcerebral electric current revealed
      protective stress-limiting action, determined by activation of nuclear and
      protein-producing cell mechanisms, which reflects on stress-releasing hormones
      synthesis and modulation. This expresses in the increase of secretory granules
      number, their significant enlargement, on hormone deponetion in neuron bodies
      with neuronal tolerance to disturbing stress effect growing higher.

PMID- 8983505
TI  - [The projections of the ventral field of the tegmentum mesencephali, substantia
      nigra and amygdaloid nuclei to different segments of the putamen in the dog].
AB  - Organization of protections of the complex "substantia nigraventral tegmental
      field" (SN-VTA) to dorsal and ventral segments of rostral and caudal regions of
      putamen was studied in dog by method based on retrograde axonic transport of
      horseradish peroxidase. A difference is found in organization of projections of
      subcortical formations studied both in rostro-caudal and dorso-ventral
      directions. Only compact SN part projects to putamen rostral region dorsal
      segment and both compact and dorsal SN parts--to this region ventral segment.
      Apart from these two parts of lateral SN area also project to putamen caudal
      regions dorsal and ventral segments. Limbic system structures projections to
      putamen dorsal and ventral segments make a significant difference as well. VTA
      and amygdala were found to project only to putamen anterior and posterior regions
      ventral segments and not to dorsal. Putamen rostral region ventral segment
      receive projection from all fibres from neurons of macro- and mediocellular parts
      of amygdala basal nucleus to the same extent and same segment located more
      caudally--mostly from its macrocellular part. In putamen ventral segments SN
      projection fibres end too and thus on this area overlapping of functionally
      different subcortical formations projections occurs.

PMID- 8983506
TI  - [The ultrastructural characteristics of the sensorimotor synapses in the
      amphibian spinal cord].
AB  - The present electron microscopic study aims to analyse sensomotor synapses
      ultrastructural peculiarities in part deafferentation and neuroplasmic transport
      to horse-radish peroxidase through the sectioned dorsal radix. Three zones of
      primary afferent fibres endings, including motor nuclear zone were found in the
      amphibian spinal cord. The data obtained demonstrated the probability of both
      chemical and combined (electrochemical, mostly of axodendritic type) origin of
      synapses, formed by primary afferent fibres on motor neurons somato-dendritic
      membrane. Complex synapses are likely to acquire peculiar importance in
      deafferentation. These data correlate with microphysiological research on
      amphibians sensomotor synaptic contacts.

PMID- 8983507
TI  - [The ultrastructure of Mauthner's neurons in the surviving medulla oblongata of
      goldfish].
AB  - Ultrastructure of Mauthner neurons (MN) was studied in fragments of
      myelencephalon incubated for 0.5-1.5 hours obtained from immature gold fish.
      Incubation terms increase along with destruction extent and reorganization of
      cytoplasmic organelles and nucleus with structure of MN afferent synaptic
      apparatus less disturbed. Specialized synaptic contacts-active zones, cleft
      contacts and desmosome-like structure are well retained. The data obtained
      indicate MN viability during the incubation terms studied, which allows to use
      surviving grafts with MN as a model for studying ultrastructural bases of certain
      functional changes of neurons and other neurobiological problems.

PMID- 8983508
TI  - [The ultrastructural characteristics of olfactory receptor cells with different
      levels of sensitivity].
AB  - Structural and functional properties of the animals olfactory analyzer were
      studied on different stages of their life. Attention was drawn to defining the
      correlations between the ultrastructure of primary sensory cells, their
      sensitivity and realization of adaptive behavior in fish in diverse reproductive
      period stages. Structural organization in fish olfactory cells appearing during
      spawning aim both to activate these cells to provide specific receptor function
      during intercourse and to urgently abolish it when transitioning to paternal
      behaviour. Not only central mechanisms of nervous system but also reorganizations
      of peripheral chemoreceptive apparatus are of great importance, which is
      demonstrated for the first time.

PMID- 8983509
TI  - [The morphological differentiation of murine neuroblastoma NIE-115 cells].
AB  - Characters and kinesis of mouse neuroblastoma (MN) cells morphological
      differentiation affected by non-serum, hypo- and hyperosmotic media and salt
      solution were studied. The nature of morphological differentiation was found not
      to depend on the inductors, while kinesis varies significantly. Morphological
      differentiation speed is directly proportional to the extent of non-specific
      action and probability of the following cell death. on the other hand, the number
      of irreversibly differentiated cells is inversely proportional to the action
      strength. For the induction of morphological differentiation a minimal nutrition
      media do not containing serum is sufficient and a common growth media changed
      once in 3-5 days according to how it acidifies is better to use for the prolonged
      maintenance of it. Universality of neuronal morphological differentiation is
      under discussion according tot he data obtained from MN cells and cultured
      mollusk isolated neurons.

PMID- 8983510
TI  - [The neuronal theory and new concepts of the structure of the nervous system].
AB  - An analysis of neuron theory modern state was carried out on the base of data
      from literature and available material. The idea of anatomic, functional and
      biochemical polarity self-dependence of a neuron and its histochemical polarity
      have changed significantly. It is said to be confirmed that neuron does not work
      on its own, its trophics is impossible without glia and one neuron may contain
      not one but several mediators combined with modulators and regulatory
      neuropeptides. Postulates on the nervous system module organization seems to be
      the most well-grounded.

PMID- 8983511
TI  - [The reactions of neuroepithelial cells in different parts of the brain in mouse
      embryos to the action of ionizing radiation].
AB  - Dynamics of neuroepithelial cells reaction was studied in different areas of
      brain obtained from mouse embryos affected by X-rays irradiation on 10th, 12th
      and 13th days of pregnancy. It was shown that as differentiation starts after the
      irradiation regeneration processes arise along with cell death. This develops in
      all brain areas due to total mitotic division of unchanged neuroepithelial cells.
      Forming of rosettes on proliferative centers is mainly characteristic for the
      forebrain. After the irradiation of mice at 1-2 days pregnancy rosettes form only
      in rostral part of anterior encephalic vesicle. In irradiation on 13th pregnancy
      day a significant number forms in rostral, lateral and dorsal parts of the
      embryonic forebrain. Irradiation on the 14th day causes the forming of the
      rosettes in the forebrain ventral part.

PMID- 8983512
TI  - [Neurosecretory activity and the dynamics of the lipid content in the CNS neurons
      in the bivalve mollusk, Gray's mussel (Crenomytilus grayanus Dunker)].
AB  - Neurosecretory process was studied in the aspect of lipid exchange in the CNS
      ganglia in the bivalve mollusk using light optics, electron microscopy,
      cytological and biochemical methods. Neurosecretory material forming was shown to
      be followed by changes in volume in neuron, nucleus and nucleolus, increase of
      nucleolar-plasmic relations, granular endoplasmic reticulum proliferation of
      mitochondria and complex dictyosomes. Changes in lipid content are inversely
      proportional to the neurosecreted amount in the neuron. The more active secretory
      process is, the smaller grows the number of lipid-containing cells, common lipids
      phospholipids. It is concluded that lipids structurally and energetically
      maintain the neurosecretory material synthesis.

PMID- 8983513
TI  - [The structural organization of the receptor elements and organs of the land
      mollusk Pomatia elegans (Prosobranchia)].
AB  - The general structural organization, receptor and nervous elements of tentacular
      sensory organs, statocysts, eyes, osphradium as well as receptor elements of skin
      of body and head were investigated in the land prosobranch mollusk Pomatias
      elegans. The structure of eyes, statocysts and osphradium of P. elegans, with the
      exception of some details, does not differ principally from the structure of
      corresponding sensory organs of the primarily water-dwelling Prosobranchia. The
      head tentacles are complex, specialized sensory formations, similar to tentacular
      organs of land pulmonates. They had a specialized sensory area, featured in the
      apex of the tentacle, and apical and basal tentacular ganglia. The glomerula-like
      formations are revealed in the neuropile of the apical tentacular ganglion.
      Almost all the receptor cells in skin and sensory organs of P. elegans are intra
      epithelial. The regularities of evolution of chemosensory systems of gastropods
      arising at multiple land intrusion are discussed.

PMID- 8983514
TI  - [The rhythms of the neuronal microstructures in the crayfish and their
      physiological significance].
AB  - The rates of functional, energetic and plastic processes running in a single
      nerve cell from the isolated crayfish mechanoreceptor were studied using original
      methods of intravital quantitative microscopy. Transitional processes of
      functional regime change in the nerve cell are followed by energy-dependent
      alteration of soma and axon hillock diameter. Synchronization between excitation
      rates and those of cell energetics growth increases the biosynthesis and protein
      content in cell.

PMID- 8983515
TI  - [The intramural neural apparatus of the mesenteric lymphangion of the small
      intestine].
AB  - Concentration of nerve structures in the lymphangion wall directly correlates
      with myocyte number in its different regions. Maximal adrenergic and cholinergic
      fibres concentration was defined in valvular torus muscular cuff of the
      lymphangion and minimal--in the valvular sinus wall. Besides, as structural
      organization of adrenergic plexus does not differ from that of
      antichollinaestherase-positive one and electron microscopic photos display
      diverse cholinergic and monoaminergic mediator vesicles in same fibres a
      suggestion is made on the mixed mediator nature of intramural plexuses of the
      lymphangion.

PMID- 8983516
TI  - [Transfusion at home? An alternative to the day hospital].
AB  - In response to the needs of the Home Medical Services a project was set up in the
      Hemobiology Transfusion Service of Beaujon Hospital. The objective of this
      project was to avoid the difficult transfer of patients who were receiving for
      the most part palliative treatment. This required strict organization between
      consultants, haemobiologist physicians and healthcare personnel. The exclusion
      criteria have been respected (geographical distance, state of the non-compensated
      clinic, absence of family/patient cooperation). During the last 4 years of
      activity, 1,662 transfusions have been carried out on 757 patients, of which 80%
      had hematological affections, 10% solid tumours and 10% AIDS affections. 5,548
      blood components have been transfused (2,104 red cell concentrates, 3,152 pooled
      platelet concentrates and 292 apheresis platelet concentrates). Thirty-one minor
      incidents were observed representing a prevalence of 0.56%. The poor codification
      of cases has slowed down the development of this project. The centralization of
      requests with coordination by the haemobiologist physicians within the Paris
      region should allow a guaranteed response to the numerous requests.

PMID- 8983517
TI  - [The direct antiglobulin and elution tests: evaluation of quality control in
      Blood Transfusion Centers].
AB  - The Societe Francaise de Transfusion Sanguine and the Centre National de
      Reference pour les Groupes Sanguins performed a quality control to evaluate the
      performances of two serological tests: the Direct Antiglobulin Test (DAT) and the
      Elution test. Among the 110 Blood Transfusion Centers participating in this
      control, 80 (73%) returned a result. Of these, 68 results were correct for the
      DAT (85%; positive for type IgG) and 31 results were correct for the elution
      (39%; anti-FY1). This control gave the opportunity to confirm the main procedures
      used in routine testing on a national scale. The analysis of the results
      underlines the importance of the choice of a standardized technique for these
      tests. Such controls are useful to appreciate the quality of the routine tests
      and to find the means to improve them.

PMID- 8983519
TI  - [The yeast flora of blood-sucking mosquitoes].
AB  - Yeast flora composition has been studied in natural populations of blood-sucking
      mosquitoes of genera Aedes. Anopheles and Culex dwelling in the territory of
      Ukraine. The authors have distinguished 18 yeast species belonging to 7 genera.
      Species Candida famata, C. (Yarrowia) lipolytica as well as the yeast of genera
      Rhodotorula and Cryptococcus dominate on the larvae and imago of mosquitoes. The
      distinguished strains are the components of normal microflora of blood-sucking
      mosquitoes and take no pathogenic effect on the laboratory culture of mosquitoes
      Aedes aegypti.

PMID- 8983518
TI  - [Severe hemolysis related to an association of erythrocyte allo- and
      autoantibodies in a thalassemia patients].
AB  - Alloimmunization to red cell antigens and haemolytic transfusion reactions may
      occur after red blood cell transfusion. We describe a case of life threatening
      postransfusion hyperhaemolysis in a beta thalassaemia patient. For many years,
      transfusion therapy was stopped but the patient developed a profound anaemia
      which required splenectomy. At that time, the serum contained a red cell
      alloantibody with anti-KN3 specificity. In vivo red cell survival studies were
      performed trying to determine the capacity of this antibody to cause red cell
      destruction. Unfortunately, these studies triggered again an intense haemolytic
      process explained by the appearance of red cell auto- and alloantibodies. This
      case underlines a possible link between the development of alloimmunization and
      the induction of potentially serious autoimmune haemolytic anaemia.

PMID- 8983521
TI  - [The effect of live cultures of Bacillus subtilis on body nonspecific
      resistance].
AB  - Alive cultures of Bacillus subtilis, antagonists of pyogenic microflora, have
      been studied for their effect on functional activity of macrophagal cells and
      induction of endogenic serum alpha-interferon in the female mice of the SBA line.
      It is established that even a single intravaginal and intraperitoneal
      introduction of bacilli in a dose of 1 milliard cells in 0.1 ml of cultural fluid
      stimulates migration, absorption and especially bactericidal activity of
      macrophages of peritoneal exudate. Introduction of alive cultures of aerobic
      bacilli essentially stimulates the in vivo production of the serum and alpha
      interferon induced in vitro by the Newcastle disease virus. The highest immune
      stimulating effect under a single introduction of B. subtilis is achieved 66 h
      later and has a tendency to gradual decrease.

PMID- 8983520
TI  - [Enterobacteria in areas of water along the Crimean coast].
AB  - Characteristic of coliform bacteria in the coastal sea ecosystems is given. A
      decrease of Escherichia coli indicator value was ascertained and presence of
      Klebsiella sp. and Citrobacter freundii was revealed, in the sea areas with high
      level of anthropogenic load. Wide distribution of bacteria of Enterobacter
      agglomerans kind was determined in the sea substrates and their stability to
      unfavourable influences was shown.

PMID- 8983522
TI  - [The antitumor action of antibiotics produced by Streptomyces globisporus 1912
      studied in a model of Guerin's carcinoma in rats].
AB  - Streptomyces globisporus 1912 produces anthracycline-like antibiotics inhibiting
      the growth of gram-positive bacteria. 6-7 compounds can be separated from crude
      culture extract by means of thin-layer chromatography. The compound with Rf 0.33
      can act as the antitumor antibiotic against Guerin carcinoma of rats.

PMID- 8983523
TI  - [A comparative analysis of the effect of Bordetella pertussis preparations on a
      primary culture of murine peritoneal macrophages].
AB  - The paper deals with comparative analysis of the effect of corpuscular pertussis
      vaccine (CPV), pertussis dialysate antigen (PDA) and its fraction 2 (fr. 2 PDA)
      on primary culture of peritoneal macrophages of mice. It is established that CPV
      possesses the expressed cytotoxic effect that is of dose-dependent character. PDA
      and 2 (fr. 2 PDA), in contrast to CPV had not such an effect. Only very high
      doses of preparations (100 micrograms by protein) evoked weak toxic effect on
      macrophages. Strict direct correlation between cytotoxic effect of pertussis
      preparations on the primary culture of peritoneal macrophages of mice and their
      capacity to induce leukolymphocytosis that permits recommending application of
      these cells to estimate toxicity of pertussis preparations and prediction of
      potentiality of development of side effects under their introduction.

PMID- 8983524
TI  - [Microbial associations in Trichomonas urethritis].
AB  - The results on isolation of associated microflora from 190 patients suffering
      from Trichomonas urethritis are given. Microorganisms belonged to the species:
      Mycoplasma hominis. Ureaplasma urealyticum. Streptococcus pyogenes. Escherichia
      coli. Klebsiella pneumoniae. Proteus mirabilis. Moraxella lacunata. Acinetobacter
      Calcoaceticus and Candida. Staphylococcus cultures which were isolated from 100%
      patients belonged to 8 species: Staphylococcus aureus, S. intermedius, S.
      haemolyticus, S. epidermidis, S. capitis, S. hominis, S. warneri, S.
      saprophyticus. Most of Staphylococcus cultures had pathogenic features. Structure
      of Trichomonas vaginalis and interaction between them and associated microflora
      were studied by electron microscopy.

PMID- 8983525
TI  - [The determination of phosphoethanolamine and other amino components in the
      lipopolysaccharides of gram-negative bacteria by ion-exchange chromatography].
AB  - A method for analysis of phosphoethanolamine in hydrolysates of the fractions
      structural parts of lipopolysaccharide macromolecule on the column with cation
      exchange resin Ostion LG ANB (CSFR) in the system of step gradient of sodium
      citrate buffers is suggested, optimal conditions for acidic hydrolysis of
      polysaccharide-standard were chosen to determine phosphoethanolamine and other
      amino compounds contained in it. The conditions for chromatography analysis of
      phosphoethanolamine together with aminosugars and amino acids have been
      developed. Using the suggested procedure the presence of phosphoethanolamine was
      found in preparations of lipid A hydrolysates and core oligosaccharide isolated
      from some lipopolysaccharide strains of Pseudomonas fluorescens.

PMID- 8983526
TI  - [The use of monoclonal antibodies and a biotin-streptavidin system of
      amplification for the quantitative determination of human IgE].
AB  - A "sandwich"-variant of the solid phase immunoenzyme method of quantitative
      determination of human IgE in biological liquids has been developed on the basis
      of two monoclonal antibodies to various epitopes of Fc-fragment of E-chain of
      human IgE and biotin-streptavidin system of the signal amplification. The total
      analysis time is 3 h: the range of determined concentrations of IgE is 1-200
      kE/l; sensitivity-1 kE/l; the type of calibrating curve is linear. To make an
      analysis twice 10 microliters of the tested sample are required. Reproducibility
      of the suggested method is not below 5%.

PMID- 8983527
TI  - [Yeasts contaminating salmon roe].
AB  - Quantitative and species compositions of yeast contaminating eggs, fry and
      fingerlings of Salmo gairdneri Rich under artificial breeding have been studied.
      Prevalence of species of genera Candida, Rhodotorula, Cryptococcus and
      Debaryomyces is noted. Yeast isolated from perished eggs and sick fry do not
      possess pathogenic properties. Certain strains of yeast make stimulating effect
      on the studied microorganisms.

PMID- 8983528
TI  - [Chorioretinal lymphoproliferative disorder induced by Epstein-Barr virus in lung
      transplantation].
AB  - The Epstein-Barr virus (EBV) is the causative factor of the posttransplant
      lymphoproliferative syndromes. Some ocular cases were described. We report the
      case of a lung-transplanted 59 year old man who presented a chorioretinal
      lymphoproliferative syndrome. A B-cell monoclonality and numerous EBV genome
      copies were demonstrated in vitreous material by PCR. We suspect an intermediate
      stage between polyclonal lymphoproliferative syndrome and malignant lymphoma. A
      treatment with nucleoside analogs and immunosuppression decrease was successful.
      The positive clinical evolution was associated with a reduction of the EBV genome
      quantity.

PMID- 8983529
TI  - [Myelin fibers in Zairian patients].
AB  - PURPOSE: to determinate the characteristics of myelinated nerve fibres in Zairian
      blacks patients. METHODS: a review of records of patients with myelinated nerve
      fibers seen from 1962 to 1994. RESULTS: the relative incidence of myelinated
      nerve fibers was 0.02%. There were 13 (76%) male patients and 4 (24%) female
      patients. The average age at the moment of diagnosis was 32 years (range, 7 to 61
      years). Myelinated nerve fibers were bilateral in 8 (47%) patients (16 of 25
      eyes, 64%) and unilateral nerve fibers, 21 (84%) eyes contained a single lesion
      and 4 (16%) eyes contained multiple separate and distinct patches of myelinated
      fibers. Continuous lesions were present in 21 (84%) eyes and discontinuous
      lesions in 4 (16%) eyes. The 25 affected eyes varied in refractive error from a
      spherical equivalent of + 1.5 to - 16.00. The distribution of refraction was:
      emmetropia in 2 (12%) patients (2 eyes, 8%), simple myopia in 4 (24%) patients (5
      eyes, 20%), myopia over 6 D with amblyopia in 6 (35%) patients (10 eyes, 40%),
      hypermetropia in 5 (29%) patients (8 eyes, 32%). CONCLUSION: this study showed a
      low relative incidence of myelinated nerve fibers and the bilaterality of lesions
      was frequent.

PMID- 8983530
TI  - [Effect of local medications on intraocular pressure control following
      trabeculectomy].
AB  - Longterm administration of topical antiglaucoma therapies had been indicated to
      be a serious risk for failure of trabeculectomy through inducing a subclinical
      inflammation of conjunctival tissues and stimulating secondary fibroblastic
      proliferation. Our study had 3 main aims: (1) to check if this pejorative effect
      is present in our population of glaucomatous patients, (2) in order to improve
      the rate of surgical success in theoretically high risk patients (duration of
      topical treatment longer than 36 months), to determine the usefulness of the
      following actions: suppression of beta blocking agents 8 days before surgery,
      suppression of miotics and eventual topical administration of fluorometholone one
      month before surgery. (3) to correlate the observed clinical results to the
      cellular profile of preoperative conjunctival biopsies. We presented in a first
      step the results of a retrospective analysis including 88 trabeculectomies
      performed between January '93 and April '95 in 62 GCAO patients older than 40
      years and without any previous ocular surgery. The mean age of patients was 66,8
      years (41 to 87 years). Patients were classified into "complete success",
      "qualified success" and "failures" according to the "target" IOP was or was not
      reached in the last examination. Mean follow up was 5,8 months (1 to 26 months).
      The second prospective part of our study included 20 trabeculectomies performed
      in 16 patients we chose according to the nature, the duration of the preoperative
      topical therapy and the preoperative eventual preparation of the conjunctiva.
      This study also included a semiquantitative count of the different conjunctival
      cellular colonies in peroperative biopsies. Mean follow up of this study was 2,3
      months (1 to 5 months). 31 "complete success", 52 "qualified success" and 5
      "failure" were observed in the retrospective study. The reduction of IOP
      following trabeculectomy was statistically significant at all examinations (mean
      IOP in the last examination: 14,9 +/- 4,3 mmHg) but the level of success was not
      significantly different according to the nature, (mono against polytherapy), the
      duration of preoperative medical topical treatment, as well as the preoperative
      actions in order to improve the operative success in high risk patients.
      Preliminary results of our second prospective study did not yet show any failure
      and did not exhibit any clear correlation between the counts of the different
      cellular colonies and the level of operative success on one hand and the
      different topical therapies in the other hand. The results and limitations of
      this study were compared to those of the literature.

PMID- 8983531
TI  - [Benefits of total hypermetropia correction in patients with strabismus].
AB  - This study compared the sensory status of 23 patients (19 children and 4 adults)
      before and after treatment with total hypermetropic correction. We have shown
      that binocular improvement can be obtained in every category of strabismological
      pathology, including exotropia, with the exception of early onset micro
      strabismus. Three cases of late onset micro-strabismus (one divergent and two
      convergent) where total sensory cure was obtained are also described. We confirm
      the slow clinical progression of hypermetropia in the strabismic patient provided
      with total optical correction. The two examples reported, as well as our cursory
      review of recent literature, provide justification for the early, systematic
      prescription of total optical correction for strongly hypermetropic children (> 4
      D).

PMID- 8983532
TI  - [Role of topical anesthesia in strabismus surgery].
AB  - The use of topical anesthesia for strabismus surgery can be useful in selected,
      cooperative patients. This technique is always performed on an ambulatory basis,
      and the surgical time rarely exceeded 30 minutes. One of the major advantages of
      this type of procedure is the ability to adjust the sutures during the operation.
      The presence of diplopia is a major indication for topical anesthesia. The use of
      Gracis grids has proved extremely useful for assessing the dynamic evolution of
      the diplopia over the various visual fields during the operation. This allows the
      surgeon to better control his correction, with horizontal, vertical, or torsional
      diplopia. Finally, this study shows that a precise clinical examination allows
      excellent results while limiting surgery to a single muscle (in 12 of the 14
      cases).

PMID- 8983533
TI  - [Disparity of fixation in asthenopic syndrome].
AB  - This study provides the first description of a test of fixation disparity that
      can be used in daily clinical practice. Exploration of this problem lays a basis
      for understanding, and allows rational prescription of the use of small prisms
      for the treatment of asthenopia associated with horizontal heterophoria. The
      fixation disparity is opposite to the heterophoria in almost 30% of cases. The
      test has a specificity of 71,5% for a study population of 55 patients. When the
      disparity test was abnormal, use of this examination demonstrated that the
      prescription of an adapted prism was effective in all cases in eliminating the
      disparity. This prescription usually involved asymmetric prisms. We also found
      that complaints of non-specific neck and back pains tended to improve in parallel
      to the improvement in the asthenopia and the elimination of the disparity. We
      feel that these postural pains ares part of the asthenopia related to symptomatic
      heterophoria. The ability to study disparity in daily clinical practice will also
      provide the physician with a means to study the genetic relationships underlying
      tropias and phorias when disparity is abnormal.

PMID- 8983534
TI  - [Unusual manifestation of Horton's disease: apropos of 2 case reports].
AB  - Giant-cell arteritis is a polysymptomatic disease of the elderly. We report 2
      patients, with positive temporal artery biopsy for giant-cell arteritis and
      unusual ocular manifestations. The first patient present an unilateral, acute
      ischaemic ocular and orbital syndrome partially cortico-resistant. The second one
      present a right Horner syndrome appeared several months after an important
      malaise, weights loss and pharyngeal and maxillary pain which had been
      successfully treated with antibiotics and non steroid anti-inflammatory drugs. We
      discuss the diagnostic and therapeutic management of giant-cell arteritis in our
      patients, with a review of the literature.

PMID- 8983535
TI  - [Exophthalmias in Zaire].
AB  - PURPOSE: To determinate the frequencies of causes of exophthalmos in Zaire.
      METHODS: In a retrospective study, the records of 129 patients with exophthalmos
      seen from 1986 to 1994 were reviewed. All patients were examined
      ophthalmologically and most of them medically. X-Rays, orbital CT Scan, were
      performed most frequently. RESULTS: The sex distribution was: 79 (61%) male
      patients and 50 (39%) female patients. The sex ratio being 1.50/1. The ages of
      patients ranged from one to 68 years. Unilateral exophthalmos was frequent (76%
      of cases). Tumors were present in 42% patients, followed by inflammatory diseases
      in 26% of patients, thyroid eye disease in 9% and traumatic aetiology in 1.6%;
      the etiology was not determined in 14%. Retinoblastoma (8%), lymphoma (7%) and
      rhabdomyosarcoma (5%) were the most frequent tumors seen. Orbital cellulitis
      (26%) was frequently associated with adjacent sinus infection. CONCLUSION: The
      etiologic factors found in this study could be compared to those published in the
      World with the exception of orbital cellulitis and retinoblastoma that showed a
      high incidence in this study.

PMID- 8983536
TI  - [Clinical aspects, treatment and prognosis in endophthalmitis following cataract
      surgery: apropos of 13 cases].
AB  - Post cataract endophthalmitis is a rare but serious complication. We propose a
      therapeutic scheme in first intention and further submit some prophylactic rules.

PMID- 8983537
TI  - [Posterior scleritis: apropos of 6 cases].
AB  - In a retrospective study of 6 patients (9 eyes) with posterior scleritis, we
      analyse the symptoms, the clinical signs and the ancillary tests of the disease.
      A decreased vision and an ocular or periocular pain are found in 8 cases of 9.
      Anterior involvement like redness is found in all the cases. In 7 eyes, we
      observe a diffuse or localized exudative retinal detachment. B-scan
      ultrasonography is the most helpful ancillary test, showing in all the examined
      eyes a scleral thickening. In 2 patients, we find a systemic disease associated
      with the posterior scleritis.

PMID- 8983538
TI  - [Fetal alcohol syndrome and bilateral uniform posterior haze of the cornea].
AB  - A boy aged 12 prematurely born presents several signs of fetal alcohol syndrome
      (FAS): mild mental retardation, staturoponderal delay, microcephaly, thin
      philtrum and vermillion of the upper lip. The ophthalmological aspects are:
      telecanthus, retinal vascular tortuosity, hypoplastic optic discs, hypermetropia,
      and an uniform, diffuse posterior haze on both corneas. This haze, which is not
      described till now as part of the syndrome, is not present in the other members
      of his family. Radiologic and biologic investigations (namely the profile of the
      urinary and seric amino acids, the urinary organic acids, and the research for
      mucopolysaccharides) are normal. Karyotype is normal as well as the research for
      fragile X which is negative.

PMID- 8983539
TI  - [Normovolemic hemodilution in central retinal vein thrombosis. Personal
      experience apropos of 14 cases].
AB  - The treatment of the central retinal vein occlusion (CRVO) is a debated question.
      Isovolaemic haemodilution known for its beneficial effects on the tissue
      microcirculation has shown encouraging results. A first study on 14 patients
      seems to indicate beneficial effects of isovolaemic haemodilution versus
      spontaneous evolution.

PMID- 8983540
TI  - [Cataract extraction in uveitis].
AB  - As a frequent and important complication of uveitis, cataract poses a number of
      problems concerning surgical indications and techniques. This report discusses
      thirty patients operated for cataract as a complication of uveitis. The
      intervention was performed on eyes which had been quiet for six months.
      Sarcoidosis and Fuch's heterochromia were the principle etiologies. In some cases
      however, the etiology was unknown. Surgical methods and results are discussed. IN
      CONCLUSION: if particular indications are respected and if adequate postoperative
      anti-inflammatory treatment is provided, surgery for cataract secondary to
      uveitis has a relatively good prognosis.

PMID- 8983541
TI  - [Massive subretinal hemorrhage in the course of age-related macular degeneration:
      preliminary study].
AB  - We retrospectively studied 58 eyes with a subretinal haemorrhage > or = 5 disc
      areas related to age-related macular degeneration. The subretinal new vessels
      which caused the haemorrhage were occult or mixed except in 2 cases of well
      defined new vessels where the haemorrhage appeared after a trauma. A pigment
      epithelium detachment was present in 1/3 of the cases before the haemorrhage. 36%
      of the patients had one or more important haemorrhagic recurrences. In 32% of the
      cases, the visual acuity before the haemorrhage was > or = 4/10. The final
      evolution resulted in an important fibroglial and atrophic central scar with a
      dramatic loss of visual acuity (85% VA < 0,1).

PMID- 8983542
TI  - Patients' health related quality of life before and after aesthetic surgery.
AB  - OBJECTIVES: To assess the health related quality of life of patients before and
      after aesthetic surgery. DESIGN: A survey by questionnaire of patients before
      receiving surgery and 6 months after surgery. SAMPLE: 656 patients anticipating
      surgery were sent a preoperative questionnaire, to which 443 replied.
      Subsequently 259 of these received a postoperative questionnaire, of which 198
      were returned. OUTCOME MEASURES: Health status was assessed using three
      standardised health status instruments (The Short Form 36 Health Survey
      Questionnaire (SF-36), the General Health Questionnaire (GHQ-28) and the
      Rosenberg Self Esteem Scale. Comparisons were made between the health status of
      the plastic surgery patients and that of a random sample of the general
      population. RESULTS: Patients receiving breast reduction surgery experienced
      significant improvements on all three health status measures. Patients in all
      surgical groups experienced significant improvements in self-esteem. CONCLUSIONS:
      Patients receiving aesthetic surgery experience a wide range of physical,
      psychological and social problems. Surgery was shown be effective at addressing
      these problems. Health status assessment provides a valid and independent method
      for measuring the effects of such health care interventions.

PMID- 8983543
TI  - "The reason for hating myself": a patient's request for breast reduction.
AB  - A recent script from a patient highlights the problems often experienced by
      patients with an oversized bust and who wish for breast reduction. This may be of
      assistance in discussing contracts and the ever present threat of rationing.

PMID- 8983544
TI  - Reduction mammaplasty with the inferior pedicle technique: early and late
      complications in 371 patients.
AB  - A review of reduction mammaplasties with the inferior pedicle technique in 371
      patients over 10 years is presented and the complications associated with this
      particular technique are discussed. The mean age was 33.1 years (range 15-67),
      the average preoperative sternal notch to nipple distance was 30.4 cm (range 21
      43), the mean breast tissue resected was 870 g per breast (range 250-1960) and
      the mean operating time was 3.1 hours (range 2.5-4). The overall complication
      rate was 11.4%. The incidence of specific complications in our series was:
      haematoma 0.3%, nipple and/or pedicle necrosis 0.8%, wound dehiscence 4.6%, fat
      necrosis 0.8%, carcinoma 0.5%, loss of sensitivity of the nipple 1.3%,
      hypertrophic scars 3.3%, dermoid cysts 0.3% and marked lower fullness 0.3%. 72%
      of the patients that became pregnant were able to lactate.

PMID- 8983545
TI  - Pathological findings in breast reduction surgery.
AB  - A retrospective analysis of pathological findings in 157 female patients
      undergoing breast reduction is presented. In 33 months 295 breasts were reduced.
      25.6% of these patients had an abnormal pathology report, but no cases of
      premalignant disease or breast cancer were found. A postal questionnaire sent to
      consultant members of the British Association of Plastic Surgeons in 1994 found
      89% routinely sent breast reduction tissue for pathological study. 42% had seen
      at least one case of breast cancer reported from this tissue. Recommendations for
      the use of pathology in breast reduction surgery are proposed.

PMID- 8983546
TI  - Surgical treatment of lagophthalmos in facial palsy: ear cartilage graft for
      elongating the levator palpebrae muscle.
AB  - Ocular exposure, conjunctival irritation and corneal keratitis are disturbing
      consequences of facial paralysis with lagophthalmos. Many techniques have been
      described for correcting this condition. A new method for decreasing the
      palpebral fissure is presented. An ear cartilage graft is interposed between the
      tarsal plate and the levator palpebrae superioris muscle. 12 patients with
      paralysis of the orbicularis oculi muscle, as assessed by electromyography, were
      treated with this technique. The palpebral fissure was decreased by 2-3 mm in all
      cases. 11 patients showed significant improvement of their eye symptoms. One
      patient, in whom the palpebral fissure could not be closed sufficiently to
      protect the eye, required additional lengthening by 4 mm of the cartilage graft
      and a lateral tarsorrhaphy.

PMID- 8983547
TI  - Objective evaluation of the Tajima secondary cleft lip nose correction.
AB  - The early and late results of the Tajima cleft nose correction were objectively
      measured by computer on 24 unilateral complete cleft lip and palate patients (age
      range 5-29 years, median 14). Follow-up records were divided into early (within 3
      months), intermediate (3 months to 1 year) and late (1 year+); the longest follow
      up was 4.2 years. Comparison of the preoperative records with the early and
      intermediate follow-up photographs showed an improvement in symmetry (Wilcoxon
      signed rank, P < 0.01). In the late follow-up group the deformity recurred and
      the nasal shape could not be statistically separated from the preoperative
      appearance. A group of 25 normal control faces showed no changes, whilst 20
      control cleft patients had some worsening of nasal symmetry over the same time
      scale. Analysis of the components of the corrected noses showed the best
      improvement (and later relapse) was in dome symmetry.

PMID- 8983548
TI  - Refinement of the Fries and Webster modifications of the Bernard repair of the
      lower lip.
AB  - Refinement of the Fries and Webster modifications of the Bernard principle for
      reconstruction of the lower lip is described. The refinement consists of changing
      the direction of the incision from the angle of the mouth, which is made along a
      line passing laterally and curving downward, instead of slightly upward. This
      refinement has been used in 15 cases, seven with unilateral and eight with
      bilateral flaps. The functional results of this modification match the results of
      the original Bernard (Fries, Webster) technique. The aesthetic results are better
      because the suture line is sited along the fold of the angle of the mouth in a
      downward direction, which is more natural.

PMID- 8983549
TI  - Reconstruction of cupid's bow with bilateral vermilion flaps.
AB  - A technique to reconstruct the cupid's bow of the upper lip using bilateral
      vermilion flaps is presented. This technique is useful in cases where the cupid's
      bow is absent after surgery or trauma.

PMID- 8983550
TI  - Expanded free scalp flap.
AB  - Expansion of a large free scalp flap before transfer can allow direct closure of
      the flap donor site, thereby avoiding the need for a skin graft or local flap to
      close the donor site. A case is presented of anterior scalp reconstruction with
      an expanded posterior scalp free flap.

PMID- 8983551
TI  - Gustatory sweating in a free flap.
AB  - A case of Frey's syndrome arising in a free radial forearm flap used to
      reconstruct a defect in the parotid region is reported. To our knowledge, Frey's
      syndrome, although common following parotidectomy, has not been reported in a
      free flap. It is possible that parasympathetic secretomotor fibres gained access
      to the fasciocutaneous flap via the cutaneous nerve stumps in its edge, resulting
      in gustatory sweating.

PMID- 8983552
TI  - Chondrodermatitis nodularis chronica helicis et antihelicis.
AB  - A retrospective study of 50 patients (25 male, 25 female) suffering from
      chondrodermatitis nodularis chronica is presented. There was equal distribution
      between male and female, with the nodule being situated on the helix in 36 cases
      (23 male, 13 female), and on the antihelix in 18 cases (4 male, 14 female). Four
      patients had bilateral lesions. All the patients complained of severe pain in the
      affected ear when they slept on it at night. Of the 54 ears in this study, 23 had
      undergone previous surgery for the complaint. These recurrences occurred when
      either skin alone, or a disproportionately large piece of skin relative to
      cartilage, was excised. A treatment technique is described involving minimal skin
      excision combined with extensive cartilage resection. There has been no
      recurrence following our technique and postoperative deformity has been minimal.

PMID- 8983553
TI  - The quadrifoliate flap: a combination of scapular, parascapular, latissimus dorsi
      and scapula bone flaps.
AB  - A short arm stump was lengthened with a composite flap with four different tissue
      units based on the subscapular artery.

PMID- 8983554
TI  - Poland's syndrome and vascular malformations.
AB  - Unilateral hypoplasia of the breast and the pectoralis muscle with a missing
      anterior axillary fold as part of Poland's syndrome are of major concern,
      especially for women. The latissimus dorsi is one of the most suitable flaps for
      breast and anterior thorax reconstructions but it may be hypoplastic or absent.
      If so, a free tissue transfer of the contralateral latissimus dorsi muscle is the
      next possible option for reconstruction. As Poland's syndrome is additionally
      associated with vascular malformations of the diseased hemithorax such as
      hypoplastic or missing vessels, a preoperative angiography is mandatory for
      planned microvascular tissue transfer.

PMID- 8983555
TI  - Absorbable skin graft staples: a clinical trial using Graftac-X.
AB  - Skin stapling devices are a quick, effective method for securing skin grafts in
      burns patients. Removal of staples can be painful, often requiring a general
      anaesthetic. This problem has led to the recent development of absorbable staples
      which extrude with time. A prospective controlled clinical trial was performed on
      20 burns patients comparing absorbable skin tacks with stainless steel staples.
      An area of at least 50 cm2 was grafted in each patient, half of which was secured
      with absorbable tacks and half with stainless steel staples. Each patient
      therefore acted as his/her own control. The presence of infection, haematoma and
      graft take using a grided cellophane sheet were assessed at one week. Infection
      and excess scarring at tack sites were assessed at one month. A statistically
      significant difference was not found between either group. In our hands
      absorbable skin staples have proven to be a reliable method of securing skin
      grafts.

PMID- 8983556
TI  - Duplication of the urethral meatus: case report of distal hypospadias and a
      glandular urethra.
AB  - An unusual example of congenital fistula of the distal urethra presenting in a 3
      year-old boy is described. The likelihood of this deformity being a variant of
      hypospadias is explored and theories of the embryology of the anomaly are
      discussed.

PMID- 8983557
TI  - Merkel cell carcinoma of the skin.
AB  - Primary neuroendocrine carcinoma of the skin or Merkel cell carcinoma is an
      aggressive primary neoplasm. It is commonly seen in the elderly, on the head,
      neck and extremities, where it can mimic a benign or less malignant skin tumour.
      Pathological examination shows a generally dense growth of small dark cells, with
      immunohistochemical evidence of neuroendocrine differentiation. The microscopic
      appearance is very similar to metastatic oat cell carcinoma from the lung and
      this must be excluded by clinical means and appropriate imaging studies. In this
      study we present 13 new cases of Merkel cell carcinoma (the largest published
      series in the UK) and summarize 214 cases from the literature in which the
      survival data are given. In our series, 5 of 13 patients died from spread of the
      Merkel cell carcinoma. From this and other studies, it appears that early
      diagnosis and wide local excision may be the only way to prolong survival. No
      other adjuvant therapy has proved effective.

PMID- 8983558
TI  - Ferguson-Smith syndrome: the importance of long term follow-up.
AB  - A case is presented which highlights the importance of long term follow-up and
      early intervention in this unusual dermatosis. A 39-year-old man presented with
      an extensive tumour of his left ear and scalp. Surgery was not feasible. The
      progressive nature of the lesion eventually killed the patient.

PMID- 8983559
TI  - Breast reduction and carcinoma-in-situ.

PMID- 8983560
TI  - Supernumerary nostrils associated with cleft lip and palate.

PMID- 8983561
TI  - The dorsal metatarsal V-Y advancement flap for dorsal foot reconstruction.

PMID- 8983562
TI  - [Hypersensitivity pneumonitis: new entities].

PMID- 8983563
TI  - [Tracheal intubation using bronchofiberoscopy (experience of a hospital
      service)].
AB  - Fiberoptic endoscopy has brought about significant progress in the management of
      so-called difficult intubations. We describe the techniques applied and results
      in one hospital service performing intubation guided by fiberoptic bronchoscope
      (FB). A total of 512 consecutive intubations (64.18% men and 35.15% women)
      performed over the past 18 years were analyzed. Non-tumor related disease of the
      cervical column (28.91%) was the most frequent cause of difficult intubation
      requiring FB guidance, followed by trauma (18.16%) and technical difficulties
      (17.39%). A nasal route was used most often (80.86%). In 93.16% of cases,
      intubation was needed for surgery. Thirty-five (6.84%) complications of various
      types were recorded, and intubation was impossible in 3 (0.59%) cases. Intubation
      in patients under general anesthesia presented special technical difficulties due
      to loss of muscle tone and the need to maintain ventilation. We recommend
      intubation only in patients who are breathing spontaneously through the nose,
      using lidocaine as a local anesthetic and a large caliber endotracheal tube with
      as small a tip as possible.

PMID- 8983564
TI  - [Primary tumors of the thoracic wall (1991-1994)].
AB  - Between 1991 and 1994, 582 operations were performed in our service; 19 (3.26%)
      were on primitive tumors of the chest wall. We analyze the data for these
      patients, including age, sex, clinical findings, chest images, diagnoses, therapy
      and course. Ten tumors were benign and 9 were malignant. The most frequent
      clinical findings were pain and/or tumor. Diagnosis was achieved before surgery
      in only 2 cases. Except when there are clear macroscopic and X-ray signs that the
      tumor is benign, we performed broad exeresis of the chest wall, sometimes also
      resecting adjacent structures. The defect was repaired directly in 12 cases. The
      defects were covered by prostheses and/or muscle plasty in the remaining
      patients. The most frequent tumor was chondrosarcoma (3 cases), followed by 2
      cases of osteoblastoma and osteochondroma. Only 1 each of the following tumors
      were found: plasmocytoma, chondroma, fibrous dysplasia, eosinophilic granuloma,
      osteosarcoma, Ewing's tumor, epithelioid sarcoma, fibrosarcoma, hemangioma,
      benign neurilemmoma, desmoid tumor and liposarcoma. Two patients with
      chondrosarcoma were operated on for recurrences and there was also recurrence in
      the patient with Ewing's tumor. We conclude that: 1) chest wall tumors are
      infrequent, 2) radical exeresis is the treatment of choice and prosthesis is
      often necessary, and 3) chondrosarcoma, with poor outcome in our patients, is the
      most frequent tumor.

PMID- 8983565
TI  - [Bronchoplasty in bronchopulmonary tumors. Review of 50 cases].
AB  - Bronchoplasty in oncological surgery is performed to remove a tumor while
      preserving most of the pulmonary parenchyma. Survival in selected patients is
      similar to survival after lung removal. We report a series of 50 bronchoplastic
      procedures performed in 37 patients with bronchopulmonary cancer. Twelve had
      carcinoid tumors and 1 had single lung metastasis from adenocarcinoma of the
      colon. Twenty-seven operations were performed on the right side and 23 on the
      left. The pulmonary parenchyma was not resected in 2 patients. The pulmonary
      artery was also repaired in 5 patients. Mortality at 30 days was 2% (1 patient)
      and survival at 5 years was 47% calculated according to the method of Kaplan
      Meier. Survival was 37 months in only 1 of the 8 patients with mediastinal
      adenopathy, for whom complementary radiation therapy was provided. Survival among
      the patients with carcinoid tumors is 91.6% to date, as all but 1 are alive at
      present. The single death was due to intestinal diverticulosis. The patient with
      metastasis is alive 12 years after surgery. Spirometric function tests were
      performed in 17 patients 1 year after surgery and ventilation perfusion was
      studied in 13. A slight loss of forced vital capacity and maximum expiratory
      volume in 1 second, while ventilation perfusion corresponding to the parenchyma
      preserved was normal. Bronchoplasty is the treatment of choice for endobronchial
      tumors with low degrees of malignancy. Bronchoplasty is an effective surgical
      treatment for a select group of carcinomas.

PMID- 8983566
TI  - [Necrotizing descendent mediastinitis of oropharyngeal origin].
AB  - The spread of oropharyngeal infections to the mediastinum can give rise to
      descending necrotizing mediastinitis (DNM), which causes a high rate of mortality
      (around 40%), particularly when diagnosis is late and drainage inadequate. In the
      first case we report, successful drainage of the mediastinum was achieved at the
      cervical and sub-xiphisternum levels and by thoracotomy. Given the condition of
      the second patient, transcervical drainage alone was considered the best option,
      but this treatment was inadequate. Rapid start of appropriate drainage of the
      mediastinum is of great importance. Cervical drains, which may be adequate when
      there is perforation of the cervical esophagus, is insufficient in DNM, which
      calls for more aggressive, early drainage, such as can be achieved by
      thoracotomy. Computerized axial tomography of the chest is essential for rapid
      diagnosis, to plan the most appropriate surgical approach and for follow-up and
      evaluation of drainage.

PMID- 8983567
TI  - [Theophyllines of 12- and 24-hour sustained-release. Comparative study].
AB  - To compare 24-h and 12-h delayed-release theophylline in asthmatic patients, in
      terms of clinical stability and respiratory function, side effects and required
      dose, clinical tolerance and plasma concentrations. Patients with bronchial
      asthma in stable phase taking theophylline every 12 h were selected. Each patient
      received 12-h (treatment A) and 24-h (treatment B) theophylline formulas in a
      prospective, cross-over study with paired data for periods of 15 days. We
      evaluated theophylline doses, blood levels, clinical course, lung function and
      side effects. Twenty patients were enrolled. No significant differences between
      the two treatments were observed in mean dose of theophylline per kg body weight
      required to obtain therapeutic plasma concentrations (treatment A: 9.36 +/- 1.88
      mg/kg/day; treatment B: 9.6 +/- 1.7 mg/kg/day). Mean blood level just before
      administration of a the next dose was lower with the 24-h formula, but still
      within therapeutic margins (treatment A: 7.31 +/- 2.27 micrograms/ml; treatment
      B: 10.66 +/- 2.86 micrograms/ml; p = 0.002). There were no differences in side
      effects after the adjustment period or in FEV1 after each treatment period. Peak
      expiratory flow remained stable during the study. The 24-h delayed release
      theophylline formula was similar to the 12-h formula in dose required by
      asthmatic patients and in therapeutic plasma concentrations throughout the day.

PMID- 8983568
TI  - [Artificial mineral fibers and respiratory disease. Scientific Committee on
      Airbone Insulating Mineral Fibers].

PMID- 8983569
TI  - [A new device for measuring occlusion pressure].
AB  - Mouth pressure in the first 100 ms of inspiration with the airway occluded (P0.1)
      is an indirect measure of central airways activity. Few adequately validated
      devices are available on the market for measuring this variable automatically,
      impeding wider use of this measurement. Our aim was to determine the validity and
      precision of a new automatized manometer for measuring P0.1 and compare the
      device to the apparatus normally used in our laboratory. The newly manufactured
      device consisted of a semiconductor type pressure transduce connected to an
      analog-to-digital converter. The usual apparatus used was constructed in our
      laboratory from a Honewell transducer, an analog-to-digital card (Data
      Translation DT2801) for an IBM-compatible PC and a standard spread sheet program.
      Both devices recorded a continuous signal at a sample frequency of 100 Hz. To
      determine linearity, accuracy, sensitivity and precision, two columns of 5 and 25
      cmH2O were used. For clinical assessment, 33 patients scheduled for lung function
      analysis were tested. Five measurements of P0.1 were performed on each. The
      sensitivity of the new device was 0.1 cmH2O; precision expressed as a variation
      coefficient was 0%, and linearity expressed as a correlation coefficient was r =
      0.999 between the two columns. The mean difference between the two devices was
      0.11 (0.46) cmH2O (p < 0.0001). Analysis of concordance confirmed a reading bias
      for the new device in comparison with the usual one, although the difference was
      not clinically significant (0.08 to 0.14 cmH2O). We conclude that the new device
      gives good results and its availability on the market may allow more frequent
      clinical application of occlusion pressure measurement.

PMID- 8983570
TI  - [Desensitizing treatment in bronchial asthma].

PMID- 8983571
TI  - [Croup and tracheotomy].

PMID- 8983572
TI  - [Tracheobronchial amyloidosis: apropos of 3 cases].
AB  - We report 3 cases of tracheobronchial amyloidosis starting with post-obstructive
      pneumonitis, suggesting underlying neoplasm. The diagnosis was by fiberoptic
      bronchoscopy. We also describe radiological findings and their usefulness,
      therapeutic options, and course of disease.

PMID- 8983573
TI  - [Pleural effusion as initial presentation of rheumatoid arthritis. Cytological
      diagnosis].
AB  - A 24-year-old woman with an unremarkable history presented with a large right
      sided pleural effusion. Analysis of the pleural fluid showed a sterile exudate
      with a low sugar level. Complementary analyses were unable to pinpoint the
      etiology. The effusion was drained and the patient was released with no specific
      diagnosis. Nine months later the effusion recurred and the initial laboratory
      analyses were the same. Pleural fluid cytology revealed the presence of an
      amorphous necrotic background and non-small cells with multiple nuclei, two signs
      that constitute part of the pathognomonic triad of rheumatoid pleural effusions,
      the third characteristic benign fusiform histocytes. The biochemical
      characteristics of the pleural fluid thus suggested rheumatoid pleural effusion,
      and cytology confirmed the diagnosis. Corticoid therapy effected spectacular
      recovery, but when the dose was reduced, rheumatoid symptoms presented in the
      joints. Rheumatoid arthritis should be considered as a possible explanation for
      unexplained pleural effusion. Cytology must be used for diagnosis.

PMID- 8983574
TI  - [Strongyloides stercoralis infection in a cortico-dependent patient with chronic
      airflow obstruction].
AB  - We report a case of Strongyloides stercoralis infection in a male agricultural
      worker with corticoid dependent chronic obstructive air flow disease and
      bronchial hyperreactivity. The clinical picture initially involved digestive
      symptoms and bronchospasm resistant to steroid treatment. Diagnosis was
      established by demonstrating the larvae of S. stercoralis in stool. We emphasize
      that this infection should be suspected in patients living in endemic areas such
      as Spain, and describe S. stercoralis-caused respiratory manifestations that can
      be masked by bronchial disease.

PMID- 8983576
TI  - [Pulmonary tuberculosis with diaphragm involvement].

PMID- 8983575
TI  - [Pneumocystis carinii pneumonia in an HIV patient with negative exercise oxygen
      desaturation test].

PMID- 8983577
TI  - [Tracheal bronchiole].

PMID- 8983578
TI  - [Tumor necrosis factor alpha in pleural fluid in patients with pleural
      tuberculosis. Relation with human immunodeficiency virus infection].

PMID- 8983580
TI  - Commentary: radiation protection supervisors.

PMID- 8983579
TI  - [Family planning centers in France: health resource centers for adolescents and
      young adults].
AB  - Family planning centres can play a more extensive role than simple reproductive
      health, in particular for adolescents and young adults. They can become true
      health and counseling centres. In France, state supported family planning centres
      were officially created in 1972; they had been preceded by initiatives developed
      by non-profit associations. The centres have both educational and medical
      functions, in the areas of contraception and fight against sterility; since 1990
      they have also integrated STD (sexually transmitted diseases) prevention and
      treatment into their mandates. Family planning centres offer free consultations
      to adolescent minors, without requiring adult authorization. Overall, young
      people under the age of 20 account for 25 to 40% of the family planning centre
      clientele, although they represent only 16% of the potential user population.
      Females are more likely to frequent the centres than males: one young women in 10
      under 20 consults per year, as opposed to only one young man in 400. This is the
      case for 3 centres in the north of France, which were the objects of the study
      presented here. In the centres participating in the study, 80% of the clientele
      were under 20, with the vast majority being under 128 years of age. The
      availability of contraceptive devices has evidently reduced the reasons for
      frequenting the centres. As 1 youth in 4 is not yet sexually active however, the
      preventive role for these centres is obvious and well recognised by the young
      people. The study indicated that one adolescent among 17 frequents the centres
      for either health problems or counseling not necessarily having to do with
      sexuality; some go merely to find someone to talk to. Reasons for these choices
      most often cited are the assurance of confidentiality and lack of fees. The
      availability of counsellors, the possibility to consult alone or in a group the
      possibility to consult without an appointment, the quality of the reception, and
      the central location of the centres were also cited as important. What the young
      people appreciated in the family planning centres is exactly what they seek in
      general health service centres. It is not surprising, therefore, that they use
      the family planning centres as primary care structures.

PMID- 8983581
TI  - Commentary: radiation protection for radiologists.

PMID- 8983582
TI  - Review article: effects of radiation on the cell proliferation kinetics of
      epithelial tissues--therapeutic implications.
AB  - The cell kinetic responses of the epithelia of the skin, oral mucosa and
      intestine to photon irradiation are reviewed. One of the fundamental assumptions
      made in the development of mathematical models, used to predict the acute
      response of normal tissues to changes in fractionation protocols, is "equal
      effect per fraction". There is now accumulating cell kinetic data to indicate
      that this assumption is unlikely to be valid. The implications of these findings
      are discussed.

PMID- 8983583
TI  - The clinical and radiological features of cholecystocolic fistulae.
AB  - The clinical and radiological features of seven patients presenting with
      cholecystocolic fistulae are reviewed. The majority of the patients were elderly
      (age range 43-85 years, mean 70.7 years) and there was a female preponderance
      (6:1). The condition usually has a benign clinical course. Diarrhoea was the most
      common presenting symptom and the typical clinical features of gallbladder
      disease were absent. Cholangitis occurred in only one patient. The time between
      onset of symptoms and diagnosis varied from 1 week to 2 years (mean 22 weeks). In
      only one patient was the diagnosis of biliary-intestinal fistula suspected on the
      basis of the plain abdominal radiograph (Case 5). A diagnosis of cholecystocolic
      fistula was established by barium enema (5 cases), endoscopic retrograde
      cholangiopancreatography (ERCP) (1 case) and diagnostic laparotomy (1 case). The
      only cause identified in this series was acute or chronic cholecystitis.

PMID- 8983584
TI  - Colour Doppler ultrasound in renal artery stenosis: intrarenal waveform analysis.
AB  - Renal artery stenosis (RAS) is the commonest secondary cause of hypertension and
      may result in renal ischaemia with resultant renal failure. Recent studies hve
      suggested that colour Doppler ultrasound, with spectral analysis of the
      intrarenal waveforms, can identify those patients with a significant RAS. A
      prospective study was performed in which colour Doppler ultrasound was compared
      with angiography in 73 patients (143 kidneys) presenting for renal angiography.
      Colour Doppler ultrasound was unsuccessful in 16% of kidneys due to a combination
      of technical failures and small kidney size. Accessory renal vessels were present
      in 14% of kidneys on angiography but none was detected by ultrasound. Of the 120
      kidneys that had both examinations, no significant difference in intrarenal
      pulsatility or resistive index was noted between the angiographically stenosed
      and normal arteries. There were significant differences for intrarenal peak and
      end diastolic velocities, and acceleration time and index. Of these measurements,
      acceleration time was the best indicator of RAS. The probability of detecting a
      high grade RAS in an individual patient did not reach 90% until the acceleration
      time was prolonged to more than 0.12 s. Intrarenal colour Doppler ultrasound is
      not a general screening test for RAS and it should be reserved for selected
      patient groups where the incidence of disease is high. Patients with prolonged
      acceleration times of more than 0.12 s have a high likelihood of at least 70% RAS
      and should proceed directly to angiography.

PMID- 8983586
TI  - Localization of the prostatic apex for radiotherapy planning: a comparison of two
      techniques.
AB  - Autopsy and pathology studies have shown that the caudal portion of the prostate
      gland harbors tumour in 64-75% of specimens examined. Accurate localization of
      the prostatic apex may be important in improving local control with external beam
      radiation therapy. We compared the location of the apex obtained with CT based
      treatment planning versus localization using retrograde urethrography in 32
      consecutive patients. The prostatic apex, localized by CT and retrograde
      urethrography, was compared relative to the ischial tuberosities and the
      symphysis pubis. Discordance between the location of the prostatic apex as
      defined on CT scan and retrograde urethrography was found in 50% of patients
      evaluated. There was 31% discordance between the location of the prostatic apex
      as defined on CT and retrograde urethrography when data were analysed with the
      location of the prostatic apex 1 cm above the narrowing on urethrography, a
      definition others have suggested. The urethrogram defined prostatic apex, as
      compared with the CT definition, necessitated the treatment of more of the
      surrounding normal tissues in 31% of our cases, with four-field techniques.
      Comparison of dose-volume histograms of the bladder, rectum and penis irradiated
      for target volumes defined by CT versus retrograde urethrography showed that more
      penis was irradiated in some patients with the urethrogram defined prostatic
      apex; irradiation of the base of the penis could be relatively avoided by using a
      six-field treatment plan instead of the standard four-field box. There is
      discordance between the CT and urethrogram defined prostatic apex. Dose-volume
      histogram information suggests that differences in apex localization can
      significantly affect doses to normal adjacent prostatic tissues. Combining CT
      localization with the urethrogram localization of the prostatic apex optimizes
      radiotherapy planning and dose delivery.

PMID- 8983585
TI  - Concordance and precision of dual X-ray absorptiometry with a 10 s scan.
AB  - Development of dual energy X-ray absorptiometry (DXA) scanners with multidetector
      array technology has resulted in greatly shortened scanning times. The Hologic
      QDR-4500 includes an ultrafast (10 s) "turbo" scan mode recommended by the
      manufacturer for fast screening studies or as an aid to positioning the patient
      prior to scanning using the normal fast (30 s), medium (1 min) or high definition
      (2 min) modes. The suitability of the turbo mode for use in routine clinical
      studies was assessed by examining the concordance of bone mineral density (BMD)
      measurements obtained in this mode with measurements obtained using the three
      normal scanning modes. Studies in 151 female patients showed statistically
      significant discrepancies in four out of the six scan sites studied with
      systematic differences of 2.9% and 3.1% being observed for the posteroanterior
      (PA) spine and intertrochanteric region of the hip, respectively. In vivo
      precision for the 10 s scan found by performing duplicate measurements on 37
      patients had a coefficient of variation of 1.3% for PA spine and 2.5% for femoral
      neck BMD. An investigation of the dependence of precision on body mass index
      (BMI) shows that the precision of spine and hip BMD was adversely affected with
      increasing BMI but the trend was statistically significant only in the spine. It
      was concluded that turbo mode scans are acceptable for routine clinical studies
      of the spine and hip but should not be used for longitudinal studies or patients
      with BMI greater than 30 kg m-2.

PMID- 8983587
TI  - The reduction of tumour control with increasing overall time: mathematical
      considerations.
AB  - The rate of loss of tumour control (dP/dt) with extension of treatment time is
      analysed to assess the relative contributions of radiobiological parameters
      (radiosensitivity, clonogen doubling time, clonogen numbers and fractionation
      schedule) on such loss. Linear quadratic modelling and Poisson statistics are
      used to study individual tumour responses. A heterogeneous tumour population is
      constructed by the use of random sampling techniques to allow for variations in
      intrinsic radiosensitivity and clonogen doubling times. Average tumour control
      probability is calculated for this population for two different fractionation
      schedules (60 Gy in 30 fractions and 50 Gy in 15 fractions), each given over 15
      60 days. The magnitude of dP/dt will depend upon the tumour cure probability (P):
      the loss of control will be most significant for tumours which have a cure of 37%
      when the Poisson survival model is used. The analysis suggests that compensation
      for short unscheduled treatment gaps (e.g. by increasing the total dose or
      rescheduling with use of weekend treatment sessions) may only be required for
      difficult tumours (i.e. radioresistant and/or with short clonogen doubling
      times). Where pre-treatment clonogen numbers are relatively low as in small
      volume tumours or after surgical debulking, the model predicts that correction
      for short treatment gaps is probably not required if the average effective
      clonogen doubling times are longer than 5 days. Different dose-time-fractionation
      schedules, even though producing similar overall cure rates in clinical practice,
      may actually be achieving cures in different subpopulations within a population
      of tumours, since the value of dP/dt in each individual tumour will depend upon
      the set of radiobiological parameters given above. For a hypothetical randomly
      selected heterogeneous tumour population the predicted rates of loss of tumour
      control produced by an extension in treatment time are 0.9 and 1.1% per day,
      respectively, for the above fractionation schedules. These values are close to
      those reported in the clinical literature for the first 2 weeks of treatment
      prolongation (1-2% per day for squamous cell carcinomas). The Poisson method,
      when combined with random sampling techniques, consequently provides realistic
      data. Modelling of this clinical problem provides an insight into how tumour sub
      populations, each characterized by its own set of radiobiological parameters, can
      influence the overall rate of loss of tumour control in a heterogeneous
      population. Random sampling techniques should be considered as necessary
      precursors for the assessment of the choices of dose-fractionation in future
      clinical trials particularly when more precise data regarding the radiobiological
      parameters and their statistical variations become available.

PMID- 8983588
TI  - Long-term cardiac mortality after radiotherapy of breast cancer--application of
      the relative seriality model.
AB  - Effects on the heart constitute a potentially significant and serious clinical
      problem in primary radiation therapy of early breast cancer. Increased cardiac
      mortality among irradiated patients may offset the potential benefit in terms of
      a reduced risk of recurrence or of death from breast cancer. Clinical data on
      long-term cardiac mortality among breast cancer patients included in two
      randomized trials (the Stockholm and Oslo studies) of radiation therapy as an
      adjunct to primary surgery were analysed using the relative seriality model of
      radiation response. Five different radiation therapy techniques were used in the
      trials. The original treatment plans were recalculated on a group of model
      patients using a three-dimensional treatment planning system. A mean dose-volume
      histogram (DVH) was calculated for each treatment technique. Both heart and
      myocardium, i.e. excluding circulating blood within the heart, were separately
      investigated as risk organs. Model parameters, (D50, i.e. the dose giving 50%
      complication probability; gamma, i.e. the maximum relative slope of the dose
      response curve; s, describing the organ relative seriality) were determined by a
      chi 2 fitting of the calculated probability of excess cardiac mortality, based on
      the DVHs, to the incidence data. Computed complication probabilities for each
      treatment technique were modelled within the 95% confidence interval (CI) of the
      clinical incidence data. It was shown that the relative seriality model, assuming
      a homogeneous radiation sensitivity within the volume of the heart/myocardium can
      be used to describe the incidence data. A small dependence on the volume was
      found. The results do not, however, exclude the possibility that more sensitive
      structures within the myocardium are the main target for radiation.

PMID- 8983589
TI  - Risk factors and dose-effect relationship for osteoradionecrosis after
      hyperfractionated and conventionally fractionated radiotherapy for oral cancer.
AB  - A high frequency of osteoradionecrosis after hyperfractionated radiotherapy (RT)
      of head and neck tumours led to a detailed analysis of risk factors in the
      dental, surgical, and radiotherapeutic areas. 168 patients with oral cancer were
      analysed retrospectively. 19% of them had been irradiated primarily and 81%
      postoperatively. 116 patients received a total dose mostly ranging from 60 Gy to
      70 Gy to the ICRU 29 reference point (daily single dose 2 Gy). 52 patients were
      treated hyperfractionally with two daily fractions of 1.2 Gy per day, 4 h minimum
      apart and a total dose 82.8 Gy. Dental findings could be evaluated in 126
      patients. Factors were checked for prognostic significance for osteoradionecrosis
      (ORN). Dose dependency was computed using a PROBIT analysis. Dental status before
      radiotherapy was generally poor (mean 11/32 teeth present, of these 1 was dead,
      2.4 carious, 2.4 loose, 0.3 destroyed). On average, six teeth (range 0-27 teeth)
      had to be extracted. In one-third of the patients bone surgery was necessary. ORN
      occurred in 8.6% of the patients treated conventionally but in 22.9% of those
      treated hyperfractionally (p = 0.029). Biologically effective dose (p = 0.032)
      and deep paradontitis (p = 0.034) proved to be significant risk factors for ORN.
      PROBIT analysis showed a steadily rising dose dependency of the ORN frequency
      after conventional radiotherapy. Using total doses up to 70 Gy the frequency of
      ORN was 8.6%. Dose escalation using hyperfractionation led to an intolerable ORN
      frequency (22.9%) where a short interfraction interval was a significant factor.
      The use of this dose fractionation was therefore discontinued in 1992.

PMID- 8983590
TI  - Dose reduction in double contrast barium enema by use of low fluoroscopic
      current.
AB  - Under standard conditions double contrast barium enema (DCBE) was carried out on
      a selected patient cohort using either standard (1.5 mA) or low (0.5 mA)
      fluoroscopic current. A statistically significant (p < or = 0.01) reduction in
      total dose was achieved by use of low screening current. This reduction was of
      the order of 40%. Fluoroscopic image quality was analysed both objectively and
      subjectively, and was found not to be significantly degraded when the lower
      current was used. On blinded evaluation all examinations were found to be of
      diagnostic quality. The use of low fluoroscopic current results in a reduction in
      patient dose, without compromising fluoroscopic image quality or diagnostic
      standard of the examination. Low fluoroscopic current technique has been adopted
      as the standard in our department.

PMID- 8983591
TI  - Short communication: use of the output video signal for dynamic range, brightness
      control and image memory assessment in X-ray fluoroscopy.
AB  - The output video signal from three X-ray fluoroscopy machines was recorded with a
      storage oscilloscope to calculate the dynamic range of their image intensifier
      television camera chains. The two MERATE MTH90 and MGR50hf machines employed the
      same imaging chain but the response of the former to exposure was significantly
      lower because of a three channel light distribution optical system which was
      installed but not used. The CGR Stenoscope machine was found to have a very
      narrow dynamic range to the extent that it was not usable. Additional
      measurements on the CGR machine showed that the image intensifier brightness
      control mechanism would produce stabilized brightness in less than 0.4 s and it
      proved to be faster than the manual selection of exposure parameters. The quality
      of the image stored in the memory device on the same system was compared with the
      original by subtracting the two video signals on the oscilloscope and thus
      acquiring a quantitative measure of their difference.

PMID- 8983592
TI  - Short communication: staff dose reduction during coronary angiography using low
      framing speed.
AB  - Radiation exposure of cardiac catheterization laboratory staff is a known
      occupational hazard, and efforts are made to obtain dose levels which are "as low
      as reasonably achievable". This study assessed the reduction in staff radiation
      exposure using cine framing at 12.5 f s-1 during coronary cineangiography,
      instead of 25 f s-1. Thermoluminescent dosemeters were used to measure equivalent
      dose at several sites for the operator, nurse assistant, and X-ray technician
      during 15 procedures at both frame rates. Patient-related and procedure-related
      variables were similar in the two groups of examinations. Mean equivalent dose
      absorbed (microSv) at the left side of the forehead was reduced by 61%, 60% and
      36%, for the operator, nurse assistant and X-ray technician, respectively. With
      use of the lower frame rate similar reductions by 42%, 62% and 62% were measured
      at the thyroid level, and by 51%, 40% and 61% at the mid-thorax level.
      Cinefilming at low frame rates during coronary arteriography allows a substantial
      X-ray dose reduction at all body sites for all staff. Use of lower frame rates
      wherever possible is of special interest since it may also reduce patient
      radiation exposure.

PMID- 8983593
TI  - Case report: abscess of the adductor muscles of the thigh--an unusual
      complication of Crohn's disease.
AB  - The occurrence of a Crohn's abscess involving the hamstring muscle group has not
      been reported previously. We report this diagnosis in a patient with ileocolonic
      Crohn's disease who had presented earlier with a presacral abscess.

PMID- 8983594
TI  - Case report: MR imaging of juvenile papillomatosis of the breast.
AB  - Juvenile papillomatosis of the breast is a benign, localized proliferative
      condition encountered mainly in young women. We describe the contrast-enhanced MR
      imaging findings, including dynamic data, of a patient with histologically proven
      juvenile papillomatosis of the breast. The pre-contrast T1 weighted sequence
      showed a hypointense lobulated mass which enhanced markedly in the post-contrast
      images. In the dynamic sequence the lesion showed a benign enhancement profile.
      The most specific feature was the presence of multiple small internal cysts, best
      shown on the T2 weighted images. This constellation of findings should suggest
      juvenile papillomatosis.

PMID- 8983595
TI  - Case report: multiple highly reflective foci in the renal parenchyma are not
      specific for pseudoxanthoma elasticum.
AB  - A characteristic appearance of highly reflective foci in the renal parenchyma has
      been reported in patients with pseudoxanthoma elasticum. We describe a similar
      patient but in addition have found two patients with a similar appearance on
      ultrasound who have no other evidence of the condition. The appearance of highly
      reflective foci in the renal parenchyma is not therefore specific for
      pseudoxanthoma elasticum.

PMID- 8983596
TI  - Case report: rupture and growth of adrenal myelolipoma in two patients.
AB  - Two cases of pathologically confirmed adrenal myelolipoma are described in
      Chinese patients. The first patient presented with tumour rupture and perinephric
      haemorrhage. The second patient was operated on 18 months after the incidental
      discovery of the tumour, due to its large size and the interval growth.

PMID- 8983597
TI  - Case report: lymphoepithelial cyst of the pancreas.
AB  - The case of a rare lymphoepithelial cyst of the pancreas is presented. The non
      specific findings on endoscopic retrograde cholangiopancreaticography, endoscopic
      ultrasound, computed tomography and magnetic resonance imaging are discussed.

PMID- 8983598
TI  - Case report: malignant teratoma in the thyroid gland.
AB  - Malignant teratomas of the thyroid gland are rare. These are highly malignant
      tumours with a high frequency of local recurrence and metastases following
      surgery. We report a case of malignant teratoma of the thyroid gland in a 35-year
      old female, who developed local recurrence immediately following total
      thyroidectomy. Despite achieving local control following chemotherapy and local
      radiotherapy, the patient developed distant relapse illustrating the aggressive
      nature of the disease.

PMID- 8983599
TI  - Case of the month: painful ankle swelling--diagnosis by MRI.

PMID- 8983600
TI  - Caval halo.

PMID- 8983601
TI  - Laparoscopic appendicectomy.

PMID- 8983602
TI  - Percutaneous transluminal angioplasty of the internal carotid artery.

PMID- 8983603
TI  - Risk factors for squamous cell carcinoma of the oesophagus.
AB  - Cancer of the oesophagus has great diversity in geographical distribution and
      incidence. The rate of oesophageal cancer has been increasing in some areas and
      the reasons for this are not clear. This review outlines fascinating
      epidemiological aspects and the risk factor for squamous cell carcinoma of the
      oesophagus. While in the Western world the effects of alcohol and tobacco are
      substantial preconditions, worldwide other factors, such as diet, nutritional
      deficiencies, environmental exposure and infectious agents (especially
      papillomavirus and fungi), play a significant role. Chronic irritation of the
      oesophagus appears to participate in the process of carcinogenesis, particularly
      in patients with thermal and/or mechanical injury, achalasia, oesophageal
      diverticulum, chronic lye stricture, radiation therapy, injection sclerotherapy
      and gastric resection before the appearance of oesophageal tumour. The
      association of Plummer-Vinson syndrome, coeliac disease, tylosis and scleroderma
      with oesophageal cancer has also been reviewed.

PMID- 8983605
TI  - Laparoscopic inguinal hernia repair.
AB  - Laparoscopic inguinal hernia repair may cause a revolution in general surgery if
      it proves to be the best treatment for inguinal hernia. Today there are several
      laparoscopic techniques that have been shown to be feasible. However, no
      information concerning long-term recurrence rates and cost-effectiveness is
      available. This review summarizes current knowledge, including all randomized
      studies that have appeared hitherto, and concludes that it is still premature to
      advocate a transition from the preferred individualized conventional technique to
      a laparoscopic technique on a large scale. However, a definite statement on the
      place of laparoscopic repair may be given in the near future in the light of
      larger randomized studies.

PMID- 8983604
TI  - Sepsis and fat metabolism.
AB  - Sepsis is a common surgical problem which can induce profound changes in the
      plasma concentrations of cytokines and hormones, leading to a catabolic state.
      Hypertriglyceridaemia and increased fat oxidation are the main features of
      altered fat metabolism encountered in this state. The endogenous catabolism of
      sepsis can be reduced by administering exogenous lipid emulsions as a source of
      metabolic fuel, although the changes in lipid metabolism associated with sepsis
      may affect the handling of these exogenous lipids. An exciting area for future
      research is an examination of the ability of lipid emulsions to reduce the
      morbidity and mortality associated with sepsis by altering immune responses, in
      addition to limiting catabolism.

PMID- 8983606
TI  - Division of the sphincter of Oddi for treatment of dysfunction associated with
      recurrent pancreatitis.
AB  - Increasing evidence suggests that motility disorders of the sphincter of Oddi may
      lead to episodes of recurrent pancreatitis in a small proportion of patients with
      the diagnosis of idiopathic recurrent pancreatitis. Over 10 years, 35 patients
      have been identified and treated for this condition. The aim of the study was to
      assess symptomatic outcome in these patients. Following the exclusion of common
      causes of pancreatitis the patients underwent sphincter of Oddi manometry.
      Patients with manometric abnormalities and three with normal manometric findings
      underwent treatment. Twenty-six patients with persistent symptoms underwent total
      division of the sphincter via open sphincteroplasty and septectomy. Patients were
      followed up according to symptoms and classed as having a cure, mild symptoms or
      no change. At a median follow-up of 24 (range 9-105) months, 15 of the 26
      patients were cured, eight had only mild symptoms and three remained unchanged.
      In the majority of patients with a good clinical outcome, manometry had
      demonstrated sphincter of Oddi stenosis. Total division of the sphincter of Oddi
      is associated with good symptomatic outcome in patients with recurrent episodes
      of pancreatitis and documented sphincter of Oddi stenosis.

PMID- 8983607
TI  - Pancreatitis in childhood associated with villous adenoma of the ampulla of
      Vater.

PMID- 8983608
TI  - Technique of laparoscopic splenectomy with a powered vascular linear stapler.
AB  - The spleen may be removed by a laparoscopic technique, although the benefits and
      associated morbidity of this approach are unknown. This study reports a series of
      28 consecutive patients (15 women; median age 39 (range 17-84) years) considered
      for laparoscopic splenectomy, because of idiopathic thrombocytopenia in 14, human
      immunodeficiency virus-related thrombocytopenia in seven, autoimmune haemolytic
      anaemia in four, lymphoma in two and chronic lymphocytic leukaemia in one. In 23
      cases dissection was completed laparoscopically, with the patient in the right
      lateral position, using a four-cannula technique. Vascular isolation was achieved
      with an Endo-GIA (powered vascular linear stapler). The spleen was removed by
      morselation within a retrieval bag (18 patients) or via either a Pfannenstiel or
      subcostal incision (five). The last 14 procedures have all been completed
      successfully in a mean operating time of 105 min with discharge from hospital
      within a median of 3 days. One patient developed a clinically apparent deep
      venous thrombosis 23 days after operation, for which he required readmission.
      Elective laparoscopic splenectomy is a feasible although technically demanding
      operation which may be performed safely and without associated mortality by
      surgeons experienced in laparoscopic techniques.

PMID- 8983609
TI  - Changing management of pyogenic liver abscess.
AB  - The case records of 23 patients who presented over a 5-year period with a
      diagnosis of pyogenic liver abscess were reviewed. Ascending cholangitis was
      implicated in nine cases, seven of which were associated with underlying
      malignancy. Haematogenous spread via the portal route accounted for five cases.
      Primary treatment included percutaneous abscess drainage in 15 patients. Whereas
      nine of the 11 patients with benign underlying pathology were managed
      successfully, the four with malignant biliary obstruction did not survive. Only
      one of the 23 patients who presented with hepatic abscess required surgical
      intervention. Percutaneous abscess drainage combined with appropriate antibiotic
      therapy is an effective means of managing hepatic abscess, but there remains a
      substantial overall mortality rate resulting from the increasing incidence of
      malignant biliary obstruction as a cause of this condition.

PMID- 8983610
TI  - Recurrence of hepatocellular carcinoma after surgery.
AB  - A total of 386 patients who underwent complete resection of hepatocellular
      carcinoma over an 8-year period were assessed retrospectively for tumour
      recurrence. Some 219 (56.7 per cent) of the patients developed recurrence.
      Patients with a greater degree of cirrhosis showed a longer interval to
      recurrence; the median (range) interval until recurrence was 7.9 (1.8-84.2)
      months in patients with a normal liver, 13.4 (2.0-79.5) months in those with
      chronic hepatitis and 16.7 (1.5-73.1) months in those with cirrhosis.
      Intrahepatic recurrence was observed more frequently in either the same (26.4 per
      cent) or the adjacent (24.8 per cent) Healey segment than in the lobe
      contralateral to the primary tumour (17.8 per cent). The presence of portal
      venous invasion and/or intrahepatic metastasis, underlying liver cirrhosis and
      perioperative blood transfusion were determined to be independent predictors of
      recurrence by multivariate analysis. Because intrahepatic spread of
      hepatocellular carcinoma occurs in a segment-by-segment manner, surgeons should
      use an anatomically wide resection within the hepatic functional reserve.

PMID- 8983611
TI  - Randomized trial of periportal peritoneal bupivacaine for pain relief after
      laparoscopic cholecystectomy.
AB  - The aim of this study was to determine whether injection of a long-acting local
      anaesthetic, in relation to the port sites at the level of the parietal
      peritoneum, would reduce postoperative pain following laparoscopic
      cholecystectomy. Patients were entered into a randomized, prospective, double
      blind study comparing the effects of a standard technique, in which bupivacaine
      (total of 20 ml, 0.5 per cent) was injected into the subcutaneous periportal
      tissue around the four port sites, and a technique in which bupivacaine (total of
      20 ml, 0.25 per cent) was injected into the subcutaneous periportal tissue as
      above with the addition of periportal parietal peritoneal injection of
      bupivacaine (total of 20 ml, 0.25 per cent). Two scores for pain, with the
      patient at rest, and on movement, were assessed 6 and 18 h after surgery using a
      visual analogue pain scale. Median pain score was significantly higher in
      patients who received standard technique (n = 40) than in those given peritoneal
      injection (n = 40) at both 6 (rest = 3.0 versus 1.0, movement = 5.0 versus 2.9)
      and 18 h (rest = 1.9 versus 0, movement = 3.2 versus 1.2). Both opiate and oral
      analgesic requirements were reduced in patients administered peritoneal
      injection, although this was not statistically significant. The addition of
      periportal injection of bupivacaine at the level of the parietal peritoneum,
      performed under direct vision, reduces pain after laparoscopic cholecystectomy.

PMID- 8983612
TI  - Cost-utility analysis of home parenteral nutrition.
AB  - An economic evaluation of home parenteral nutrition (HPN) for intestinal failure
      is presented. The cost-utility of HPN and factors affecting the cost-utility
      ratio were examined to determine whether current practice is the most efficient
      way of treating intestinal failure. Quality-adjusted life-years (QALYs) gained
      were measured using a validated health status questionnaire. The cost of treating
      a patient with intestinal failure was calculated, and marginal cost per QALY
      gained ratios were obtained. The cost per QALY for an average patient was
      approximately 68,975 pounds, but the value for patients over 55 years of age of
      about 126,865 pounds compared with approximately 58,233 pounds for those under 44
      years. Treating a patient in hospital rather than at home increased the estimated
      cost per QALY to approximately 190,000 pounds. The current practice of home care
      is about 65 per cent more cost-effective than hospital care.

PMID- 8983613
TI  - Randomized controlled trial of the effect of mannitol on renal reperfusion injury
      during aortic aneurysm surgery.
AB  - The effects of mannitol on renal impairment following infrarenal aortic aneurysm
      repair were studied. Patients received either mannitol 0.3 g/kg (n = 15) or
      saline (n = 13) as a rapid intravenous infusion before aortic cross-clamping. One
      patient in the control group developed fatal postoperative renal failure but
      there was no renal failure in the mannitol group. Two patients treated with
      mannitol died from perioperative myocardial infarction. There were no significant
      differences in postoperative blood urea level, serum creatinine concentration or
      creatinine clearance between mannitol and control groups. In patients who had
      mannitol there was a significant diuresis on the first day after operation (mean
      urine output 2250 ml) compared with before operation (1557 ml) (P = 0.007).
      Compared with controls, patients treated with mannitol had lower mean (s.e.m.)
      postoperative levels of urinary albumin (160(32) versus 500(140) mg per mmol
      creatinine; P = 0.036) and N-acetyl glucosaminidase (143(34) versus 271(70) mumol
      per mmol creatinine; P = 0.04) indicating a reduced level of subclinical
      glomerular and renal tubular damage. These data demonstrate that mannitol reduces
      subclinical renal injury following infrarenal aortic aneurysm repair.

PMID- 8983614
TI  - Colour-coded duplex assessment alone before carotid endarterectomy.
AB  - This study assessed whether carotid colour-coded duplex imaging can provide
      sufficient information to investigate patients before carotid endarterectomy. One
      hundred patients with symptomatic carotid artery disease (amaurosis fugax 24,
      transient ischaemic attack 38 and established stroke 38) were assessed by both
      colour-coded duplex imaging and arch angiography. Stenoses were graded at
      angiography using the linear method from the European Carotid Surgery Trial and
      on duplex using peak systolic velocity criteria. Angiograms were also analysed
      for any arch or intracerebral pathology which would alter surgical management. In
      defining 70-99 per cent stenoses, duplex had a sensitivity of 98 per cent,
      specificity 96 per cent, positive predictive value of 96 per cent, negative
      predictive value 98 per cent and accuracy 97 per cent compared with angiography
      for both symptomatic and asymptomatic carotids (chi 2 = 1.22, 1 d.f., P = 0.25).
      With respect to the symptomatic carotid arteries angiography gave different
      information from duplex in six patients (6 per cent): definition of 70-99 per
      cent carotid stenosis was different (four), visualization was poor on duplex
      (one) and an intracerebral aneurysm was identified by angiography. One patient
      died following arch angiography as a result of mesenteric thrombosis. Carotid
      duplex imaging alone would appear to be sufficient to assess most patients before
      carotid endarterectomy as an accurate, safe and relatively cheap investigation
      compared with angiography. In cases where duplex assessment does not allow full
      visualization of the carotid bifurcation angiography is required.

PMID- 8983615
TI  - Homocysteine: an independent risk factor for the failure of vascular
      intervention.
AB  - Hyperhomocysteinaemia is an independent risk factor for the early development of
      arterial disease. Homocysteine and cardiovascular risk factors were assessed in
      41 young and 25 older patients with vascular disease. As homocysteine may act by
      the generation of free radicals, total antioxidant capacity was measured.
      Hyperhomocysteinaemia was found in 29 per cent of patients but there was no
      difference between young and older patients. Homocysteine level was unrelated to
      other cardiovascular risk factors. Young age, diabetes and hyperhomocysteinaemia
      were independent risk factors for the failure of vascular procedures (P = 0.006).
      Patients with hyperhomocysteinaemia had raised total antioxidant capacity. The
      potential of identifying and treating a subgroup of patients with a poor
      prognosis deserves further study.

PMID- 8983616
TI  - Operative results of House advancement anoplasty.
AB  - A retrospective review of 29 patients who had an anoplasty using the sliding
      House advancement flap was carried out to evaluate the efficacy and safety of
      this new technique. Long-term symptom relief and late complications were
      determined by telephone interview. Indications for anoplasty were: stenosis (21
      cases), ectropion (four), Bowen's disease (two), keyhole deformity (two) and
      perineal fistula (one). A single House flap was performed in most patients, but
      eight required multiple flaps. Lateral internal sphincterotomy was performed
      concomitantly in 16 of 21 patients with anal stenosis. Postoperative
      complications included donor-site separation (14), urinary retention (eight) and
      sepsis (four). At a median follow-up of 28 months, 26 of 29 patients had improved
      and 24 were completely satisfied. House flap anoplasty can be used to correct
      many anoderm deficiencies with a high rate of success and patient satisfaction.

PMID- 8983617
TI  - p53 mutations in primary colorectal adenocarcinomas and liver metastases.

PMID- 8983618
TI  - Reduction of paraphimosis: a technique based on pathophysiology.

PMID- 8983619
TI  - Role of the general surgeon in a British trauma centre.
AB  - A prospective audit of trauma patients seen or treated by the Department of
      General Surgery at the North Staffordshire Hospital Trauma Centre has been
      carried out, examining both the effect of a newly established trauma centre on
      overall workload and the outcome of patients admitted with severe injury. Trauma
      comprised approximately 2 per cent of the overall general surgical emergency
      workload. General surgeons were involved in the assessment of 25 per cent of
      severely injured patients but overall operated on fewer than 10 per cent of
      patients in this group. No patient died during the study period as a consequence
      of missed or inadequately treated intra-abdominal injury. These data suggest that
      there is insufficient work to justify specialist general surgical trauma surgeons
      in the UK. When general surgical intervention is required, however, it is usually
      vital and potentially life-saving.

PMID- 8983620
TI  - Randomized comparison of sitting and prone positions for stereotactic fine-needle
      aspiration breast biopsy.
AB  - In a prospective randomized study, 103 women had stereotactic biopsies performed
      either in the prone (n = 51) or sitting (n = 52) position. Questionnaires were
      administered before and after biopsy, to measure anxiety, pain and subjective
      experience in all patients. Vasovagal reactions were scored from 0 to 2 according
      to severity. There was no significant difference between biopsies performed in
      the sitting or the prone position with regard to overall tolerance. Significantly
      more patients biopsied in the prone position (15 of 51, 29 per cent) than in the
      sitting position (seven of 52, 13 per cent) would prefer premedication before a
      repeat biopsy (P = 0.04). Of the total patient group, three women fainted, one in
      the prone position and two others in the sitting position. Breast biopsies
      performed in the prone or sitting position are equally well tolerated. Somatic
      reactions such as fainting are not a major problem during breast biopsy; however,
      attention should be focused on patient care, including information given before
      the procedure.

PMID- 8983621
TI  - Management of premenopausal women with primary breast cancer.

PMID- 8983622
TI  - Altered lymphatic drainage after lymphadenectomy or radiotherapy of the axilla in
      patients with breast cancer.

PMID- 8983624
TI  - Prospective comparison of laparoscopy, ultrasonography and computed tomography in
      the staging of gastric cancer.
AB  - A total of 103 consecutive patients with gastric adenocarcinoma was assessed for
      intra-abdominal spread of malignancy using ultrasonography, computed tomography
      (CT) and laparoscopy under general anaesthesia. Histologically proven metastases
      were to the liver in 27 patients, lymph nodes in 49 and directly to peritoneum in
      13. All modalities showed a high specificity (92-100 per cent) for each type of
      metastasis. Laparoscopy was more sensitive in detecting hepatic, nodal and
      peritoneal metastases; the relative performance of laparoscopy was best with
      regard to hepatic metastases. Ultrasonography and CT were particularly poor at
      detecting nodal and peritoneal metastases. There was no significant morbidity and
      no mortality associated with laparoscopy, which was more accurate in preoperative
      staging of gastric cancer than ultrasonography or CT.

PMID- 8983623
TI  - Duplicated vermiform appendix.

PMID- 8983625
TI  - Functional and morphological study of the cricopharyngeal muscle in patients with
      Zenker's diverticulum.
AB  - Pharyngo-oesophageal function was investigated in 12 patients with Zenker's
      diverticulum before and after cricopharyngeal myotomy with or without
      diverticulectomy using low-compliance, high-frequency oesophageal manometry. Nine
      healthy volunteers served as controls. The amount of muscle and connective tissue
      in the cricopharyngeal muscle was also measured by computerized morphometry and
      compared with findings in cadavers with no history of dysphagia. Preoperative
      manometry in patients with Zenker's diverticulum showed an incomplete relaxation
      of the upper oesophageal sphincter (UOS) (the residual UOS pressure at swallowing
      was 7.9 (range 1-20)mmHg in patients versus 0.2 (-12.5-14) mmHg in controls; P <
      0.001) and increased pharyngeal intrabolus pressure (21 (range 0-52) versus 9
      (range 0-16) mmHg; P < 0.01), with no pharyngo-oesophageal coordination
      abnormalities. Both parameters significantly decreased after myotomy. Patients
      with Zenker's diverticulum had significantly fewer muscle fibres in the
      cricopharyngeus and the muscle:connective tissue ratio was significantly lower
      (0.94 (range 0.8-1.4) in patients versus 1.5 (1.4-3.6) in controls; P < 0.05).
      This study supports the theory that Zenker's diverticulum is caused by an
      increased intrapharyngeal pressure at swallowing due to incomplete
      cricopharyngeal muscle relaxation resulting from localized sclerosis.

PMID- 8983626
TI  - Anatomy of the extrinsic motor nerve supply to mobilized segments of the
      oesophagus disrupted by dissection during repair of oesophageal atresia with
      distal fistula.
AB  - Atresia of the oesophagus occurs near to the site of convergence of the foregut
      with structures of branchial arch origin. This is a confluence of a striated
      muscle tube with a somatic nerve supply and a smooth muscle tube with an
      autonomic nerve supply. The implications, with regard to function, of denervating
      the oesophagus during operation are influenced by this anatomy. During dissection
      of a cadaver with oesophageal atresia and distal fistula, the sites of potential
      nerve injury were displayed. Damage to these nerves occurs during routine primary
      repair and may contribute to oesophageal motor dysfunction after successful
      surgery.

PMID- 8983627
TI  - Small intestinal myoelectrical activity and bacterial flora after Roux-en-Y
      reconstruction.
AB  - Small bowel myoelectrical activity and intestinal microflora were examined after
      partial gastrectomy and Roux-en-Y reconstruction in six dogs. Bacteriological
      analysis revealed a predominance of faecal bacteria. The basal electrical rhythm
      of the Roux limb was significantly decreased, while the frequency of phase III
      was increased (P < 0.05). In the bypassed duodenum, activity fronts occurred in
      only 25 per cent of experiments. Food intake led to an increase in the
      mean(s.e.m.) motility index in the Roux limb (from 46.1(9.4) to 75.0(21.5), P <
      0.05), but not in the bypassed intestine (from 27.0(3.6) to 27.8(4.1), P not
      significant). Stimulation of the hypomotile bypassed intestine with cisapride
      induced an increase in the motility index from 27.0(3.6) to 111.2(16.5) (P <
      0.001).

PMID- 8983628
TI  - Upper oesophageal sphincter function during general anaesthesia.
AB  - The effect of anaesthesia on the upper oesophageal sphincter response to acid in
      the distal oesophagus and hypopharynx, and the effect of atracurium besylate on
      acid migration into the hypopharynx, was studied in 102 patients undergoing
      elective varicose vein surgery. Group 1 (n = 48) received a general anaesthetic
      and the muscle relaxant atracurium besylate whereas group 2 (n = 54) received a
      general anaesthetic without relaxation. Upper oesophageal sphincter tone was
      significantly lower in patients receiving muscle relaxants ('sphinctometer
      output', eight versus 14, P < 0.05). Sixteen patients (16 per cent) had reflux
      into the distal oesophagus during anaesthesia (nine in group 1 and seven in group
      2, P not significant), of whom seven had reflux to the hypopharynx. There was no
      difference in incidence of hypopharyngeal acid exposure between groups. Upper
      oesophageal sphincter tone did not alter in response to reflux into the distal
      oesophagus or hypopharynx in either group. The upper oesophageal sphincter fails
      to protect the hypopharynx under general anaesthesia even if patients do not
      receive a muscle relaxant.

PMID- 8983629
TI  - Free revascularized jejunal loop repair following total pharyngolaryngectomy for
      carcinoma of the hypopharynx: report of 90 patients.
AB  - Ninety patients with carcinoma of the hypopharynx underwent pharyngolaryngectomy
      and reconstruction with a jejunal free autograft. Fifty-five patients had primary
      surgery and 35 salvage surgery for recurrence after radiotherapy. Following
      primary surgery 28 patients had postoperative radiotherapy and 27 did not.
      Complications occurred in 51 per cent of patients, the most common being necrosis
      of the jejunal graft (19 per cent); 12 per cent developed significant stenosis
      and 4 per cent died in the perioperative period. Eleven per cent of patients
      developed a fistula. The total number of complications diminished as the
      experience of the unit increased. Median follow-up was 4.9 years. Of patients
      treated with primary surgery, 48 per cent developed primary site recurrence (at 3
      years) and 53 per cent neck node recurrence (at 5 years). The tumour-specific 5
      year survival rate for all patients was 42 per cent. Following primary surgery 28
      per cent survived for 5 years and after salvage surgery the rate was 59 per cent.
      Positive resection margins and extensive neck disease adversely affected survival
      (P = 0.02 and P = 0.001 respectively). The free revascularized jejunal graft is a
      safe and predictable method of repair following total pharyngolaryngectomy.

PMID- 8983630
TI  - Laparoscopic surgery for gastro-oesophageal reflux: beyond the learning curve.
AB  - From September 1991 to October 1995, 320 Nissen fundoplications were undertaken
      laparoscopically by 12 surgeons at a single institution. To assess the
      performance of the procedure in the hands of five 'experienced' surgeons, the
      first 20 procedures performed by each surgeon or surgical trainee were excluded,
      providing a group of 174 patients for review. A short loose 360 degrees
      fundoplication was performed in all instances, with short gastric vessel division
      performed in 35.0 per cent of patients and hiatal repair in 66.7 per cent. Median
      operating time was 80 (range 30-210) min and median postoperative stay was 3
      (range 1-19) days. Sixteen procedures (9.2 per cent) could not be completed
      laparoscopically and required conversion to open surgery. Some 144 patients were
      reviewed by a scientific officer 3 months after surgery, 85 at 12 months, and 32
      at 2 years, using a standard clinical questionnaire. All but one were free from
      reflux symptoms, although 20.1 per cent reported some dysphagia at 3 months'
      follow-up; this figure declined to 11 per cent at 12 months and 6 per cent (two
      of 34 patients) at 2 years. At each follow-up interval, 91 per cent of patients
      were satisfied with the outcome of the surgery. Objective testing with
      oesophageal motility (75 patients) and barium swallow (113) studies 3-6 months
      after surgery confirmed the clinical outcome. Complications occurred in nine
      patients (5.2 per cent); four (2.3 per cent) of these required a subsequent
      operation within 30 days of surgery for bleeding (one patient), paraoesophageal
      herniation (one) and dysphagia (two). A further procedure was necessary in six
      other patients (3.4 per cent) for late problems, including paraoesophageal
      herniation (two), hiatal stenosis (three) and gastric obstruction (one). Revision
      was performed laparoscopically in two patients. The clinical results of
      laparoscopic Nissen fundoplication by 'experienced' laparoscopic surgeons were
      comparable with those of open surgery.

PMID- 8983631
TI  - Impaired gut barrier function in malnourished patients.
AB  - The gastrointestinal tract is essential to host defence, acting as a barrier to
      absorption and translocation of gut antigens, including bacteria. In experimental
      models, protein malnutrition is permissive to gut barrier failure and endogenous
      infection. A clinical correlate has not been described. Intestinal morphology and
      barrier function to food protein antigens was studied in malnourished patients.
      Thirty-five individuals were evaluated, 20 malnourished patients and 15 well
      nourished hospital controls. Morphology was assessed from endoscopic biopsies of
      the second part of the duodenum, and serum immunoglobulin (Ig) G antibodies to
      gliadin and beta-lactoglobulin were measured. No antibody to food proteins was
      evident in the control group. In contrast, serum IgG antibodies to at least one
      antigen were present in 15 malnourished patients and to both antigens in ten (P <
      0.0001 versus controls). Severely malnourished patients were more likely to have
      both antibodies present than those with mild or moderate malnutrition (P < 0.05).
      Antibody-positive malnourished patients had significantly better nutritional
      status than antibody-negative patients with malnutrition (P < 0.05). In no group
      of patients was there morphological evidence of abnormal mucosa or an
      immunological infiltrate. Gut barrier function is compromised in malnourished
      patients which suggests a mechanism that may facilitate gut-derived infection and
      sepsis.

PMID- 8983632
TI  - Randomized comparison of agents for caudal anaesthesia in anal surgery.

PMID- 8983633
TI  - Laparotomy for abdominal sepsis in the critically ill.

PMID- 8983634
TI  - Infiltration of the gallbladder bed during laparoscopic cholecystectomy.

PMID- 8983635
TI  - Number of lymph node metastases is significantly associated with survival in
      patients with radically resected carcinoma of the ampulla of Vater.

PMID- 8983636
TI  - Single-stage treatment for malignant left-sided colonic obstruction: a
      prospective randomized clinical trial comparing subtotal colectomy with segmental
      resection following intraoperative irrigation.

PMID- 8983637
TI  - Role of cytokines and growth factors in promoting the local recurrence of breast
      cancer.

PMID- 8983638
TI  - Ileocaecostomy: an alternative surgical procedure for antegrade colonic enema.

PMID- 8983639
TI  - Comparison of venous reflux in the affected and non-affected leg in patients with
      unilateral venous ulceration.

PMID- 8983640
TI  - Correlation between acute physiology and chronic health evaluation (APACHE) III
      score and immunological parameters in critically ill patients with sepsis.

PMID- 8983641
TI  - Correlation of the lipophilicity of xenobiotics with their synergistic effects on
      DNA synthesis in human fibroblasts.
AB  - The binary combination effects of DNA synthesis of human fibroblasts were
      investigated using 2,4-D with 15 xenobiotics of different chemical substance
      classes. Results were compared with previous investigations on cell growth. Each
      of the 15 chemicals tested at their no effect concentrations (NOEC's) increased
      the effects of 2,4-D on DNA synthesis. Thereby, the EC20 value of 2,4-D was
      reduced by approximately 40% in the combinations. The NOEC's of the xenobiotics
      used in the combinations varied by a factor of 1,600 and depended strongly on the
      lipophilicity of the agents combined with 2,4-D. A significant statistical
      correlation of r = 0.90 was found between the NOEC's of the 15 combined
      xenobiotics and their lipophilicity. The combination effects on DNA synthesis
      were similar to those on cell growth. The regression lines of the relationship
      between the NOEC's and lipophilicity in both assays showed only slight
      differences in the slopes. This is an additional confirmation of our hypothesis
      on a facilitated uptake of 2,4-D in the binary combinations.

PMID- 8983642
TI  - Passive Heymann nephritis: evidence that angiotensin-converting enzyme inhibition
      reduces proteinuria and retards renal structural injury.
AB  - In nonimmunological models of renal damage, abnormal traffic of proteins through
      the glomerular capillary is one of the possible causes of renal disease
      progression. Here we investigated whether in a model of immune-mediated
      glomerulonephritis long-lasting proteinuria resulted in renal structural damage
      and whether chronic treatment with perindopril, an angiotensin-converting enzyme
      (ACE) inhibitor, lowered proteinuria and retarded disease progression. Passive
      Heymann nephritis (PHN), a model of human membranous nephropathy, was induced
      with 0.5 ml/100 g of rabbit anti-Fx1 A antibody in 26 male Sprague-Dawley rats.
      Animals were then divided into two groups of 13 rats each, given daily vehicle or
      perindopril (1 mg/kg p.o). Treatment started at day 7 when proteinuria was
      already present and lasted 12 months. An additional group of normal rats was used
      as control. Renal biopsies were taken at months 8 and 12. Untreated PHN rats
      showed a significant increase in systolic blood pressure starting from month 8,
      that was normalized by perindopril administration. Urinary protein excretion
      progressively increased with time in untreated PHN rats that developed focal and
      segmental glomerulosclerosis and tubulointerstitial damage. Perindopril
      significantly reduced proteinuria and limited glomerular and tubulointerstitial
      injury. Urinary excretion of endothelin-1 (ET-1) and transforming growth factor
      beta 1 (TGF-beta 1), two major mediators of renal damage in other models of
      glomerulonephritis, increased with time in PHN but only the former correlated
      with the degree of glomerulosclerosis. The effect of perindopril on proteinuria
      and renal structural damage was associated with a significant reduction in
      urinary ET-1 but not TGF-beta 1, suggesting that ET-1 may be an important
      determinant of disease progression in experimental membranous nephropathy.

PMID- 8983643
TI  - [Comparison of 2 skin test methods for the diagnosis of allergic diseases].
AB  - Diagnosis of allergic diseases is realized by clinical history and cutaneous
      tests to determine the causative allergen. As several cutaneous test exist we
      consider necessary evaluate sensibility and specificity of epicutaneous (EP) and
      intradermic (ID) test. All open, prospective transversal study was carried out.
      The study included 45 patients suffering asthma, allergic rhinitis or both. The
      patients underwent both kind of test, with 10 allergens: Dermatophagoides
      pteronyssinus, Fraxinus, Ligustrum, Quereus, Schinus, Phleum, Amaranthus,
      Ambrosia, Artemisa. Alternaria and Hormodendrum. The mean age was 12 years. No
      difference was found comparing positive results for tree, grass, weed and molds
      allergens using both test. Instead for Dermatophagoides pt EP had 92.5% of
      sensibility and 100% of specificity, mean while ID has 100% of sensibility and
      96.6% of specificity. We conclude that ID test have greater sensibility and EP
      have greater specificity, we recommend use EP for first instance.

PMID- 8983644
TI  - [Exercise-induced asthma].

PMID- 8983645
TI  - [Prevalence of asthma: survey of a school population in Coatzacoalcos, Veracruz,
      Mexico].
AB  - In some areas of the Mexican Republic there had been done a few similar studies,
      this is going to complete the ones done before and it will help to know the
      prevalence of the asthma in Coatzacoalcos city. Because of confiability reasons,
      we used questionnaires in a directly form and taking like a patron the one used
      by Baeza and collaborators with some modifications. The investigation has been
      done in 583 students from 6 to 12 years old (309 of masculine sex and 274
      feminine sex). The investigation ranges the 5.8% of the students poblation in the
      locality. The 34% reports asthma in some time of their life, the 44% reports
      asthmatic bronchitis and the 20% chronic coughs because of exercise.

PMID- 8983646
TI  - [Mastocytosis in children. Report of 3 cases].
AB  - The mastocytosis is a disease characterized by an increase in mast cell number,
      and may present in childhood. It is classified as cutaneous or systemic
      mastocytosis. Cutaneous mastocytosis generally is selected in childhood. It is
      important to be aware of systemic complications. Systemic mastocytosis is adult
      onset and its clinical presentations is caused by histamine, leucotrienes,
      prostaglandins and other mediators' release. The treatment is directed at
      symptomatic relief. Several cases are reported at Hospital Infantil de Mexico
      Federico Gomez. Only 3 cases are presented of these benign child-onset diseases.

PMID- 8983647
TI  - [Common variable immunodeficiency. Report of a case and review of the
      literature].
AB  - A ten year old boy was referred to the allergy clinic due to a chronic history of
      upper respiratory infections, otitis media, recurrent sinusitis, wheezing and
      chronic cough that initiated at six years of age. He did have some very small
      lymph nodes in the cervical area. Serum immunoglobulins were very low which
      suggested the diagnosis of a common variable immuno-deficiency, a disease with
      features of increased susceptibility to infection, diarrhea, malabsorption and
      major complications that include bronchiectasis, autoantibody formation, and
      autoimmune disease. The patient received IVIG and has doing well.

PMID- 8983648
TI  - [Nasal eosinophilia after specific provocation in patients with perennial
      allergic rhinitis].
AB  - We studied 35 patients with perennial allergic response to know the eosinophilia
      after the nasal challenge with specific antigen. Patients were selected randomly.
      In each patient, history and clinical examination, cutaneous tests, and
      eosinophil count in nasal mucous membrane were done 30 minutes and 8 hours after
      the challenge with Dermatophagoides antigen Results showed a significant increase
      of eosinophils after the challenge (P.006). Significant differences were not
      discussed between the eosinophil counts obtained 30 minutes and 8 hours after the
      challenge.

PMID- 8983649
TI  - Presidential lecture, European Spine Society, 1995. The role of Europe in the
      spine--past and future perspectives.

PMID- 8983650
TI  - A new classification of lumbar motion segments for microdiscotomy.
AB  - Planning and performing lumbar microdiscotomy--with or without a microscope-
      requires a three-dimensional understanding of the spinal canal and its
      surrounding structures. A new disc-related classification is helpful. Lumbar
      motion segments are divided into disc, infradiscal and supradiscal levels in the
      craniocaudal plane and into medial, paramedial and lateral zones in the
      horizontal plane. Traversing roots, with or without a nerve root sheath, and
      exiting roots have specific locations to the levels and zones. A comparative
      study of conservatively and surgically treated patients showed that not only the
      size of the disc herniation but also the direction of migration of the extruded
      disc material has a bearing on the form of treatment that is indicated.

PMID- 8983652
TI  - Retrograde ejaculation after anterior interbody lumbar fusion.
AB  - Retrograde ejaculation as a complication of anterior interbody lumbar fusion was
      investigated. The diagnosis of retrograde ejaculation was made on the basis of
      interviews. Patients were informed of the risk of retrograde ejaculation
      preoperatively. At the follow-up study the patients were asked if they had
      noticed retrograde ejaculation after their operation. In one case (anejaculation)
      testis biopsy and vasography was performed. On average, the incidence of
      retrograde ejaculation as a complication of anterior interbody lumbar fusion has
      been very low, ranging from only a few cases up to 5.9% of cases involving male
      patients. We studied 40 male patients with severe low back pain retrospectively
      after they had undergone anterior interbody lumbar fusion. The mean age at
      operation was 31.9 years and the mean follow-up time 5.0 years. Retrograde
      ejaculation occurred after anterior interbody fusion in nine patients. Permanent
      retrograde ejaculation developed in seven of these patients (17.5%). These
      patients were all operated on using a transabdominal approach. Major bleeding
      during the operation (over 2500 ml) was observed in two patients. Seven patients
      with retrograde ejaculation had undergone a two-level operation (L4-SI), and
      eight patients had undergone between one and three previous spine operations.
      Retrograde ejaculation has been underestimated as a complication of anterior
      interbody fusion in multioperated low back patients. The possibility of this
      complication should be kept in mind when planning a transabdominal approach for
      interbody lumbar fusion in male patients. We do not recommend the transabdominal
      approach in male patients because of the risk of retrograde ejaculation.

PMID- 8983651
TI  - Severe sciatica: a 13-year follow-up of 342 patients.
AB  - This study involved 342 patients hospitalized because of severe, persistent
      sciatica suggestive of a lumbar intervertebral disc herniation. After standard
      clinical evaluation, EMG and myelography, 220 patients underwent lumbar
      discectomy. The remaining 122 patients were treated conservatively. Follow-up
      examinations were arranged after 1, 5 and 13 years. The study focused on the
      rehabilitation outcome in general and differences in outcome between the two
      treatment groups. Several indicators showed a rather poor outcome for sciatica
      patients during the 13-year follow-up period. In the operated group 16% had been
      re-operated because of lumbar disc herniation. True recurrence of herniation
      (same level and side) occurred in 8%. In the conservatively treated group 14% had
      undergone spinal surgery. Nearly 70% of the patients still reported sciatica.
      Self-assessed levels of low back pain were "no change/worse" for 19% in the
      operated group and for 44% in the conservatively treated group. In both the study
      groups, nearly 40% of the subjects had retired on disability pensions.

PMID- 8983653
TI  - Anterior thoracoscopic epiphysiodesis in the treatment of a crankshaft
      phenomenon.
AB  - We report our first performance of a multiple anterior thoracoscopic
      epiphysiodesis in the treatment of a crankshaft phenomenon. In the last 2 years,
      video-assisted thoracoscopy has been introduced as a new therapeutic technique in
      the field of spinal diseases. Its use has been most documented in the treatment
      of vertebral abscesses and disc herniations, while its performance in treating
      deformities is less known. The patient in our case was an 11-year-old boy with a
      7-year history of aggressive left thoracic idiopathic scoliosis that had
      previously needed three subcutaneous instrumentations and finally a Cotrel
      Dubousset-instrumented arthrodesis. Following these operations, a continuous
      clinical and radiographical evolution of the curve was recorded and an anterior
      T6-T11 video-assisted thoracoscopic epiphysiodesis was therefore performed. The
      patient did not need postoperative narcotics; Argyle chest tubes were removed
      after 48h with only 150ml of serohaematic drainage, no blood transfusion was
      required. One year after the intervention, we found a well-consolidated T6-T11
      arthrodesis with no evolution of the deformity. The endoscopic technique allowed
      us to perform an extensive anterior arthrodesis using only three small incisions,
      with a reduction of bed-confinement to 3 days and reduced postthoracotomy pain.

PMID- 8983654
TI  - In vivo measurement of implant loads in a patient with a fractured vertebral
      body.
AB  - It is not known what loads act on an internal spinal fixation device in patients
      with a fractured vertebral body. To measure the implant loads in vivo,
      telemeterized internal spinal fixators were implanted in a patient, and the
      implant loads measured for numerous body positions and activities before and
      after anterior fusion. The highest implant loads were found while the patient
      lifted both extended legs in a supine position. High implant loads were also
      measured for lateral bending during standing as well as for walking and carrying
      a load in one hand. The implant loads were small in recumbent positions. In
      contrast to findings in another patient, who was treated for degenerative
      instability, implant loads were smaller in the first months after anterior fusion
      than before. The indication for stabilization and surgical procedure strongly
      influence implant loads.

PMID- 8983655
TI  - Lumbosacral fracture dislocation in a lumberjack.
AB  - "Lumberjack fractures" normally occur in the thoracic and upper lumbar spine as a
      result of hyperextension and shear. This case, however, involves a lumberjack who
      suffered a lumbosacral fracture dislocation without neurological deficits, which
      occurred as the result of shear and hyperflexion. Due to the high degree of
      instability of this lesion, the treatment consisted of dorsoventral fusion with
      instrumentation.

PMID- 8983656
TI  - Exogenous lumbar spondylodiscitis following a stabwound injury and vertebral
      fracture. A case report and review of the literature.
AB  - Exogenous spondylodiscitis is a rare event and is usually iatrogenic. Non
      iatrogenic exogenous spondylodiscitis has been described in the literature
      following transabdominal gunshot wounds associated with injury to the intestines
      and spine. Several cases of traumatic meningitis and one of a traumatic
      meningocele following an injury of the spinal sac have been reported. No report
      of exogenous spondylodiscitis complicating a stabwound has been published. This
      is a report of exogenous spondylodiscitis following a paravertebral stabwound
      with a knife in association with a superior wedge fracture of L2.

PMID- 8983657
TI  - Acute MRI changes in infectious discitis: report on two cases.
AB  - Previous reports suggest that MRI changes should be seen within 48h of symptoms
      arising. We report on two patients with proven discitis at the L5/S1 disc. MRI
      performed within 60h of the onset of symptoms did not demonstrate evidence of
      infection and therefore did not confirm the diagnosis of discitis. The
      reliability of early MRI to confirm infective discitis is questionable. The cases
      we report on did not display any of the typical changes of discitis on MRI within
      the first 48h after the onset of symptoms. Absence of typical infective changes
      on MRI does not necessarily exclude an infection within the disc space.

PMID- 8983659
TI  - First thoracic disc herniation with myelopathy.
AB  - The case of a patient with progressive paraparesis due to first thoracic disc
      herniation is reported. He was treated successfully with anterior interbody
      fusion by the Smith-Robinson approach. An anterior approach is desirable for
      surgical treatment of T1/2 disc herniation, and up to this level the Smith
      Robinson approach, without thoracotomy, is entirely possible.

PMID- 8983658
TI  - Spinal cord compression in renal osteodystrophy.
AB  - A patient undergoing regular haemodialysis for chronic renal insufficiency
      developed neck pain followed by progressive spinal cord compression due to
      subluxation at the level C3-4. Decompression, laminectomy and osteosynthesis led
      to an almost complete recovery. A review of all the histological specimens
      suggested that hyperparathyroidism and not amyloidosis caused the vertebral
      destruction.

PMID- 8983660
TI  - Percutaneous extraction of vertebral osteoid osteoma under computed tomography
      guidance.
AB  - The authors report two osteoid osteomas of the spine treated by percutaneous
      extraction under computed tomography (CT) guidance. CT helps to localize exactly
      and extract only the nidus with no further damage to the bone. This technique is
      very promising, with a limited approach and minimal bone resection allowing a
      short hospital stay and prompt functional recovery.

PMID- 8983662
TI  - Primary osteosarcoma of the L2 lamina presenting as "silent" paraplegia: case
      report and review of the literature.
AB  - Primary osteosarcomas of the vertebral column are not common, and to our
      knowledge a total of 78 cases, mostly located in the vertebral body, have been
      previously reported. We report a primary osteosarcoma of the spine with an
      extremely rare location--the lamina of the second lumbar vertebra. The patient, a
      38-year-old woman, was admitted with paraplegia of a short duration without pain.
      Preoperatively, the patient underwent CT scanning for staging (Enneking IIB)
      followed by a needle biopsy and local preoperative arterial embolization. An
      emergency decompressive laminectomy was performed, and stabilization was carried
      out using methylacrylate. The patient showed a complete neurologic recovery.
      Combined chemotherapy and local irradiation did not prevent tumor recurrences,
      which occurred 12 and 19 months after the initial intervention and were
      associated with recurrent neurologic impairment. The patient died 19 months after
      the initial presentation, while in paraplegia, from lung metastases. Based on our
      unique observation, it seems that in primary osteosarcomas located in the
      posterior elements of the spin, the symptoms are not specific, and the disease
      may only become manifest when the tumor is no longer resectable. When the tumor
      is associated with neurologic impairment, spinal canal decompression should be
      performed even though it does not radically resect the tumor because it
      significantly improves the quality of the patient's life.

PMID- 8983661
TI  - Fibrous dysplasia of the spine with sarcomatous transformation: a case report and
      review of the literature.
AB  - A fibrosarcoma is reported in the spine of a 53-year-old man with polyostotic
      fibrous dysplasia. There was no history of endocrine disturbances and no previous
      irradiation. Malignant transformation in fibrous dysplasia is rare. A review of
      the literature reveals 101 cases of malignant degeneration occurring in fibrous
      dysplasia. We believe that this is the first report of sarcomatous change arising
      in an area of fibrous dysplasia in the spine.

PMID- 8983663
TI  - [Antibody engineering and gene therapy in cancer].

PMID- 8983664
TI  - Is there an internal cardiac renin-angiotensin system?
AB  - The beneficial effects of angiotensin converting enzyme (ACE) inhibitors in heart
      failure appear to be independent, at least in part, of their effect on blood
      pressure. The existence of a local cardiac renin angiotensin system is often
      suggested as an explanation. It has been known for some time that a substantial
      proportion of arterially delivered angiotensin I is converted to angiotensin II
      by ACE of the coronary vascular endothelium. The levels of angiotensin II in
      cardiac tissue are several times the levels of angiotensin II in circulating
      blood. Recent evidence suggests that most of the angiotensin II in the heart is
      not derived from angiotensin I in the circulation, and that most of the
      angiotensin I in cardiac tissue is generated in the tissue itself. On the other
      hand, renin mRNA levels are very low or undetectable in the normal heart. In
      addition, studies on the effects of bilateral nephrectomy on the cardiac tissue
      levels of renin, angiotensin I, and angiotensin II in pigs have indicated that
      cardiac renin originates from the kidney and that cardiac generation of
      angiotensin I and angiotensin II depends on renin from the kidney. Intracardiac
      synthesis of renin may occur under pathological conditions and during fetal
      development. The fact that angiotensins are generated by the heart raises the
      possibility of local mechanisms to regulate the concentrations of these peptides
      at certain tissue sites. For example, preliminary evidence suggests that binding
      of renin to cardiac membranes is a mechanism by which renin is taken up by the
      heart. A specific renin binding protein has been identified in cardiac tissue.
      Cardiac ACE levels may also influence local angiotensin II formation and are, in
      part, determined by the so called insertion/deletion ACE gene polymorphism. More
      detailed knowledge on the site of angiotensin generation and on its regulation
      will improve our understanding of the role of the renin-angiotensin system in
      cardiac function, hypertrophy, and postinfarction remodelling.

PMID- 8983665
TI  - The renin-angiotensin-aldosterone system and the cardiac natriuretic peptides.

PMID- 8983666
TI  - The renin-angiotensin-aldosterone system and cardiac ischaemia.

PMID- 8983667
TI  - The renin-angiotensin system and cardiac remodelling after acute myocardial
      infarction.

PMID- 8983668
TI  - Hypertension, hypertrophy, heart failure.

PMID- 8983669
TI  - The renin-angiotensin system and the heart: beyond 2000.
AB  - Renin-angiotensin is both a circulatory and a local tissue system. However, in
      most circumstances, renin present in the heart and blood vessels is taken up from
      the plasma, and the kidney is the prime source of this renin. Tissues can then
      modulate and control the production of angiotensin II. In various organs,
      angiotensin II has local actions. In the heart, working through the AT1 receptor,
      it increases contractility and may cause cardiocyte hypertrophy. Indirectly, the
      heart is also very much affected by the vascular actions of angiotensin II.
      However, the net result on the heart is the product of an important interaction
      between a large number of factors. There is little doubt that an inappropriately
      high plasma (and tissue) level of renin, related to sodium balance, is associated
      with increased left ventricular hypertrophy and cardiovascular complications. The
      genetic approach will lead to an understanding of genomic risk factors in
      hypertension and may identify control systems--at present unknown--which will
      lead to a new approach to the prevention of cardiovascular death. It is, however,
      unlikely that such a factor will clearly predict an individual's prognosis, but
      it will, rather, identify groups at risk. Constellations of genomic interactions
      with multiple environment factors reduce this power. Modification of the response
      to angiotensin II using present treatment, or interrupting the response at more
      distal sites, may enable us to achieve the beneficial effects on cardiac
      hypertrophy without the detrimental effects.

PMID- 8983670
TI  - Beyond cholesterol reduction in coronary heart disease: is vitamin E the answer?

PMID- 8983671
TI  - Alterations of coronary blood flow and myocardial perfusion in
      hypercholesterolaemia.

PMID- 8983672
TI  - Resistive vessel function in coronary artery disease.

PMID- 8983674
TI  - Helicobacter pylori seropositivity in subjects with acute myocardial infarction.
AB  - OBJECTIVE: To determine whether Helicobacter pylori infection increases the risk
      of myocardial infarction. DESIGN: Case-control study. SETTING: University
      teaching hospital. METHODS: Serological evidence of H pylori infection was
      determined in 342 consecutive patients with acute myocardial infarction admitted
      into the coronary care unit and in 236 population-based controls recruited from
      visitors to patients on medical and surgical wards. RESULTS: 206/342 (60.2%) of
      cases were H pylori positive compared with 132/236 (55.9%) of controls (P =
      0.30). Age and sex stratified odds ratio for myocardial infarction associated
      with H pylori seropositivity was 1.05 (95% CI 0.7 to 1.53, P = 0.87) and this
      remained non-significant (P = 0.46) when other risk factors for ischaemic heart
      disease were taken into account using logistic regression analysis. H pylori
      seropositivity was not associated with several coronary risk factors in either
      cases or controls. CONCLUSION: No increase was found in H pylori seropositivity
      in subjects with acute myocardial infarction. This suggests that previous H
      pylori infection is not a major risk factor for acute myocardial infarction.

PMID- 8983673
TI  - Hyperhomocysteinaemia, Helicobacter pylori, and coronary heart disease.
AB  - Hyperhomocysteinaemia and Helicobacter pylori infection have recently been
      implicated in the pathogenesis of coronary artery disease. These two risk
      factors, though they seem unrelated, could be linked by a deficiency of vitamins
      and folate caused by chronic gastritis in H pylori infection. This nutritional
      defect could lead to failure of methylation by 5-methyl-tetrahydrofolic acid and
      thus exacerbate the accumulation of homocysteine in susceptible patients.
      Homocysteine is toxic to endothelial cells and results in coronary artery
      disease.

PMID- 8983675
TI  - Jan Evangelista Purkinje (1787-1869).

PMID- 8983676
TI  - Clinically stable angina pectoris is not necessarily associated with
      histologically stable atherosclerotic plaques.
AB  - OBJECTIVE: To investigate the extent of plaque inflammation in culprit lesions of
      patients with chronic stable angina. DESIGN: Retrospective study. SETTING:
      Amsterdam reference centre. SUBJECTS: 89 consecutive patients who underwent
      directional coronary atherectomy, 58 of whom met the following inclusion
      criteria: chronic stable angina (Canadian Cardiovascular Society classification 1
      3 (group 1, n = 28)); unstable angina (Braunwald class II (group 2, n = 18));
      unstable angina (Braunwald class III (group 3, n = 12)). INTERVENTIONS:
      Directional atherectomy in patients with angina pectoris. MAIN OUTCOME MEASURES:
      Tissue areas of culprit lesions occupied by inflammatory cells and smooth muscle
      cells related to clinically defined ischaemic syndrome. RESULTS: Areas (% of
      total surface area (mean (SEM)) rich in smooth muscle cells were larger in
      patients with chronic stable angina (group 1, 51.2 (20.9)) than in those with
      unstable angina (group 2, 42.1 (20.5); group 3, 29.5 (19.4)) (1 v 2 and 2 v 3,
      NS; 1 v 3, P < 0.004). Macrophage rich areas were significantly smaller in
      patients with stable angina (group 1, 21.8 (11.9)) than in those with unstable
      angina (group 2, 31.5 (14.6); group 3, 46.4 (16.7)) (1 v 2, P < 0.02; 2 v 3, P <
      0.02; 1 v 3, P < 0.001). Mean numbers of T cells per mm2 were as follows: group
      1, 17 (9.4); group 2, 25 (15.9); group 3, 41 (30.6) (1 v 2, P 0.04; 2 v 3, P
      0.07; 1 v 3, P < 0.001). Areas with HLA-DR positive cells showed the same pattern
      as macrophages and T cells and were smaller in stable (29.9 (12.4)) than in
      unstable angina (group 2, 40.4 (17.6); group 3, 52.4 (12.0)) (1 v 2, P < 0.02; 2
      v 3, P < 0.05; 1 v 3, P < 0.001). CONCLUSION: The inverse relation between the
      extent of inflammatory activity in plaque tissues of culprit lesions and the
      clinical stability of the ischaemic syndrome supports the concept that reduction
      of inflammation favours plaque stabilisation. At the same time, the considerable
      overlap between groups indicates that patients with clinically stable angina do
      not all have histologically stable plaques.

PMID- 8983677
TI  - Use of intravascular ultrasound for in vivo assessment of changes in intimal
      thickness of angiographically normal saphenous vein grafts one year after
      aortocoronary bypass surgery.
AB  - OBJECTIVE: To use intravascular ultrasound in vivo to evaluate changes in the
      intimal thickness of angiographically normal saphenous vein grafts one year after
      implantation. DESIGN: Fifteen saphenous vein grafts in 12 patients were examined
      one month and 12 months after aortocoronary bypass graft surgery with
      intravascular ultrasound using a 30 MHz transducer. None of the grafts examined
      showed any angiographic abnormalities. The intimal thickness and intimal area of
      the graft in the proximal portion were measured on intravascular ultrasound
      images obtained one month and 12 months after operation. SETTING: General
      hospital. PATIENTS: Twelve patients who underwent aortocoronary bypass graft
      surgery. RESULTS: The ultrasound images showed a thin-walled graft with a thin
      intima one month after operation (mean (SD)) (0.31 (0.09) mm). The intimal
      thickness of the graft increased significantly to 0.65 (0.08) mm (P < 0.001) 12
      months after operation. The intimal area of the graft was 0.90 (0.80) mm2 one
      month after operation. 12 months after operation the intimal area had increased
      significantly to 5.26 (1.38) mm2 (P < 0.001). CONCLUSION: Intravascular
      ultrasound in vivo showed that one year after implantation angiographically
      normal saphenous vein grafts had a thicker intima than one month after
      implantation.

PMID- 8983678
TI  - Carotid intima-media thickness in young patients with familial
      hypercholesterolaemia.
AB  - OBJECTIVE: To assess the extent of early atherosclerotic changes of the carotid
      arteries in young patients with familial hypercholesterolaemia (FH) detected as
      increased intima-media thickness (IMT), and to determine the relations between
      IMT and some clinical and blood variables such as lipid and lipoprotein(a)
      (Lp(a)) concentration and haemostatic factors. DESIGN: The IMT of the carotid
      bifurcation, the proximal 1 cm of the internal carotid artery, and the distal 1
      cm of the common carotid artery was determined in all subjects using B mode
      ultrasonography. Blood lipids, fasting glucose, and several haemostatic variables
      were also analysed. SUBJECTS: 28 patients with FH (12 males and 16 females aged
      11 to 27 years, one homozygote, 27 heterozygotes) and 28 sex and age matched
      normolipidaemic healthy subjects. RESULTS: The mean carotid IMT (the average of
      six measurements of the maximum far wall IMT in the three carotid segments on
      each side) was significantly greater in patients with FH than in controls (mean
      (SD) 0.71 (0.15) v 0.49 (0.08) mm, P < 0.001). In all subjects, the mean IMT was
      significantly correlated with total cholesterol (r = 0.59), low density
      lipoprotein (LDL) cholesterol (r = 0.60), triglycerides (r = 0.27), and systolic
      blood pressure (r = 0.47). No correlation was found between the mean IMT and
      Lp(a), fibrinogen, tissue plasminogen activator, and plasminogen activator
      inhibitor 1. CONCLUSIONS: The majority of young patients with FH have a greater
      intima-media thickness of the carotid arteries than healthy subjects. Since the
      individual susceptibility of patients with FH to increased LDL cholesterol is
      different, B mode ultrasonography could provide a useful tool to identify those
      who are more likely to develop premature atherosclerotic disease.

PMID- 8983679
TI  - ACE inhibitors unmask incoordinate diastolic wall motion in restrictive left
      ventricular disease.
AB  - OBJECTIVE: To assess the effect of ACE-inhibition on left ventricular filling and
      wall motion in patients with a clinical diagnosis of heart failure. DESIGN:
      Prospective examination of left ventricular systolic and diastolic function using
      M mode echocardiography and pulsed and continuous wave Doppler before and three
      weeks after starting an ACE inhibitor. SETTING: A tertiary referral centre for
      cardiac disease equipped with non-invasive facilities. SUBJECTS: 30 outpatients
      with a clinical diagnosis of heart failure in whom treatment with an ACE
      inhibitor was started; age 61 (SD 11) years; 27 male; 3 female; 21 healthy
      controls of similar age. RESULTS: Left ventricular cavity was dilated both at end
      systole and end diastole, and fractional shortening reduced. Although mean
      isovolumetric relaxation time (IVRT) and transmitral E (early) to A (late)
      filling velocity (E/A) ratio were not different from normal, a value of 1.0 on
      the normal frequency plot of the E/A ratio divided the patients bimodally into
      two groups: 20 patients (group A) with E/A ratio > 1.0 and 10 patients (group B)
      < 1.0. In group A patients, IVRT was short as was transmitral E wave deceleration
      time compared to normal (P < 0.001), fulfilling the criteria of restrictive left
      ventricular physiology. Left ventricular wall motion during IVRT was coordinate
      and left ventricular end diastolic pressure was raised on the apex-cardiogram (P
      < 0.001). In group B, E wave deceleration time was longer, relaxation
      incoordinate, and apexcardiogram normal. With an ACE inhibitor: in group A, left
      ventricular dimensions fell at end diastole (P < 0.05) and end systole (P < 0.01)
      but fractional shortening did not change; long axis total excursion (P < 0.01)
      and peak rate of shortening (P < 0.05) both increased; IVRT increased (P < 0.001)
      with the appearance of markedly incoordinate wall motion, minor axis lengthening,
      and long axis shortening (P < 0.001 for both); A wave amplitude also consistently
      increased (P < 0.001); finally, transmitral E wave velocity fell and A wave
      velocity increased. ACE inhibition did not alter any of the left ventricular
      minor and long axis or transmitral Doppler variables in patients in group B.
      CONCLUSIONS: Patients with a clinical diagnosis of heart failure differ in their
      presentation and response to ACE inhibition according to baseline haemodynamics.
      In restrictive left ventricular physiology, ACE inhibition reduces cavity size
      and prolongs IVRT, compatible with a fall in left atrial pressure. At the same
      time, ventricular relaxation becomes very delayed and incoordinate, greatly
      reducing early diastolic left ventricular filling velocity. Thus ACE inhibition
      unmasks major diastolic abnormalities in patients with restrictive left
      ventricular disease.

PMID- 8983680
TI  - Inspiratory muscle endurance in patients with chronic heart failure.
AB  - OBJECTIVE: To assess the significance of changes in respiratory muscle endurance
      in relation to respiratory and limb muscle strength in patients with mild to
      moderate chronic heart failure using a threshold loading technique. SUBJECTS: 20
      patients with chronic heart failure (17 male) aged 63.8 (SD 7.4) years and 10
      healthy men aged 63.1 (5.6) years. Heart failure severity was New York Heart
      Association (NYHA) grade II (n = 11) and NYHA grade III/IV (n = 9). METHODS:
      Respiratory muscle strength was measured from mouth pressures during maximum
      inspiratory effort (MIP) at functional residual capacity (FRC) and limb muscle
      strength was measured using a hand grip dynamometer. Inspiratory muscle endurance
      was measured using a threshold loading technique. The total endurance duration,
      the maximum threshold pressure achieved (P-Max), and the inspiratory load (%
      ratio of P-Max/MIP) were recorded in all subjects. RESULTS: Inspiratory muscles
      were weaker in patients with heart failure than in the controls [MIP 53.6 (16.5)
      v 70.9 (20.2) cm H2O, P < 0.05]. Hand grip strength was similar in both subject
      groups [31.6 (SD) v 36.1 (15.9) dynes]. Total endurance duration was
      significantly reduced in the patient group [494 (223) v 996 (267) s, P < 0.01],
      as was the maximal threshold pressure achieved [P-Max 18.5 (6.4) v 30.7 (6.6) cm
      H2O, P < 0.01]. When expressed as a percentage of MIP, P-Max was also lower in
      the patients [35.2 (11.8) v 44.8 (11.4)%, P < 0.05]. There was no significant
      correlation between any measure of endurance and limb muscle strength.
      CONCLUSIONS: Respiratory muscle endurance is reduced in patients with chronic
      heart failure. These changes probably reflect a generalised skeletal myopathy and
      provide further evidence of respiratory muscle dysfunction in patients with this
      disease. Respiratory muscle endurance needs now to be related to symptoms and the
      effects of treatment and respiratory muscle training should also be explored.

PMID- 8983681
TI  - Specific changes in skeletal muscle myosin heavy chain composition in cardiac
      failure: differences compared with disuse atrophy as assessed on microbiopsies by
      high resolution electrophoresis.
AB  - OBJECTIVE: In congestive heart failure (CHF) the skeletal muscle of the lower
      limbs develops a myopathy with atrophy and shift from the slow type to the fast
      type fibres. The aim was to test the hypothesis that this myopathy is specific
      and not simply related to detraining, by comparing patients with different
      degrees of CHF with patients with severe muscle atrophy due to disuse. DESIGN:
      Case-control study involving 50-150 micrograms needle biopsies of the
      gastrocnemius muscle. By an electrophoretic micromethod, the three isoforms of
      myosin heavy chains (MHC) were separated. PATIENTS: Five patients restricted to
      bed for more than one year because of stroke with disuse atrophy and normal
      ventricular function, and 19 with CHF were studied. There were seven age matched
      controls. MAIN OUTCOME MEASURES: The percentage of MHC1 (slow isoform), MHC2a
      (fast oxidative), and MHC2b (fast glycolytic) was determined by densitometric
      scan and correlated with indices of severity of cardiac failure. RESULTS:
      Ejection fraction was 42.5 (SD 15.2)% in CHF, 59.5 (1.0)% in disuse atrophy and
      60.3 (1.4)% in controls (P < 0.001 v both). The degree of muscle atrophy as
      calculated by the body mass index/gastrocnemius cross sectional area, showed a
      profound degree of atrophy in patients with muscle disuse [0.94 (0.39)]. This was
      worse than in the controls [4.27 (0.16), P < 0.0005] and the CHF patients [2.60
      (1.10), P < 0.005]. Atrophy in CHF patients was also greater than in controls (P
      < 0.005). MHC1 was lower in CHF than in disuse atrophy [51.83 (15.04) v 84.5
      (17.04), P < 0.01] while MHC2b was higher [23.5 (7.4) v 7.25 (7.92), P < 0.001].
      There was a similar trend for MHC2a [24.83 (15.01) v 8.25 (9.12), P < 0.05].
      Within the CHF group there was a positive correlation between NYHA class and
      MHC2a (r = 0.47, P < 0.05) and MHC2b (r = 0.55, P < 0.01) and a negative
      correlation between NYHA class and MHC1 (r = -0.74, P < 0.001). Similarly,
      significant correlations were found for ejection fraction, diuretic consumption
      score, exercise test tolerance, and degree of muscle atrophy. CONCLUSIONS: The
      CHF myopathy appears to be specific and not related to detraining. The magnitude
      of MCH redistribution correlates with the severity of the disease. The
      electrophoretic micromethod used is very sensitive and reproducible. Biopsies are
      so well tolerated that can be repeated frequently, allowing thorough follow up.

PMID- 8983682
TI  - Intravascular ultrasound-guided emergency coronary Palmaz-Schatz stent placement
      without post-procedural systemic anticoagulation.
AB  - OBJECTIVE: To test the efficacy of intravascular ultrasound (IVUS)-guided stent
      placement and to determine the clinical outcome during the first 30 days in those
      patients who were treated with antiplatelet therapy rather than anticoagulants
      because they met the IVUS criteria for optimal stent placement. DESIGN:
      Prospective observational study. PATIENTS: 126 patients with successful, non
      elective Palmaz-Schatz stent placement. INTERVENTIONS: IVUS was performed to
      assess the attachment of stent struts, the coverage of the dissection, and the
      intrastent minimal lumen area. MAIN OUTCOME MEASURES: Intrastent lumen area,
      clinical outcome during the first 30 days. RESULTS: In all patients IVUS showed
      complete apposition and coverage of the dissection. In 23 patients (18%) the IVUS
      lumen area criterion was achieved. In 75 patients, further balloon dilatation was
      performed and in 41 IVUS criteria were finally fulfilled. The minimal intrastent
      lumen area increased from a mean (SD) of 6.81 (1.15) mm2 to 9.56 (2.61) mm2 (P <
      or = 0.01) between the first and final IVUS investigations. 64 patients (51%) who
      met the IVUS criteria were treated with aspirin (100 mg) and ticlopidine (250 mg)
      twice a day. During the first 30 days none of the following events occurred:
      death, myocardial infarction, repeat intervention, aortocoronary bypass surgery,
      and subacute stent thrombosis. CONCLUSION: The additional information provided by
      IVUS examination helped the operator to decide whether further dilatation was
      needed after a coronary stent had been placed. For patients who met the IVUS
      criteria for optimal stent placement, antiplatelet therapy was associated with an
      excellent clinical outcome during the first 30 days.

PMID- 8983683
TI  - Quantitative three dimensional echocardiography in patients with pulmonary
      hypertension and compressed left ventricles: comparison with cross sectional
      echocardiography and magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the accuracy of quantitative three dimensional
      echocardiography in patients with deformed left ventricles. DESIGN: Three
      dimensional and cross sectional echocardiographic estimates of left ventricular
      volume and ejection fraction were prospectively compared to those obtained from
      magnetic resonance imaging. SETTING: Echocardiography laboratory of a university
      hospital. PATIENTS: 26 patients (9 months to 42 years, median age 11 years) with
      pulmonary hypertension and fixed reversal of normal interventricular septal
      curvature. MAIN OUTCOME MEASURES: Left ventricular end diastolic and end systolic
      volumes and ejection fraction. RESULTS: Three dimensional echocardiographic
      comparison to magnetic resonance imaging (MRI) yielded r values of 0.94 and 0.87
      with a bias of -6.9 (SD 6.9) ml and -16 (11.2) ml for systolic and diastolic
      volumes respectively. Inter-observer variability was minimal (8.3% and 7.6%
      respectively). Cross sectional echocardiography gave correlation coefficients of
      0.62 and 0.80 and bias of 3.1 (14.1) ml and 16.3 (18.3) ml for systolic and
      diastolic volumes respectively. Ejection fraction by three dimensional
      echocardiography also had closer agreement with MRI (bias = 1.1 (7.7)%) than
      cross sectional echocardiography (bias = 4.4 (13.9)%). CONCLUSIONS: Three
      dimensional echocardiography provides reliable estimates of left ventricular
      volumes and ejection fraction, comparable to magnetic resonance imaging in
      pulmonary hypertension patients with compressed ventricular geometry. Because it
      eliminates the need for geometric assumptions it shows closer agreement with
      magnetic resonance imaging in that setting than cross sectional echocardiography.

PMID- 8983684
TI  - Caffeine restriction has no role in the management of patients with symptomatic
      idiopathic ventricular premature beats.
AB  - OBJECTIVE: To assess the role of caffeine restriction in the management of
      patients with symptomatic idiopathic ventricular premature beats. DESIGN: A
      randomised, double blind, 6 week intervention trial incorporating dietary
      caffeine restriction, caffeinated coffee, and decaffeinated coffee. SETTING:
      Cardiac outpatient clinic. PATIENTS: 13 patients with symptomatic frequent
      idiopathic ventricular premature beats. MAIN OUTCOME MEASURES: Weekly measures of
      serum caffeine concentration, coffee consumption, visual analogue score of
      palpitations, and 24 hour ventricular premature beat frequency. RESULTS: The
      interventions achieved significant alterations in serum caffeine concentrations
      (P < 0.001) which correlated with coffee consumption (r = 0.70; P < 0.001).
      Visual analogue palpitation scores showed a small, but significant correlation
      with ventricular premature beat frequencies (r = 0.34; P = 0.003). However, there
      were no significant changes in palpitation scores or ventricular premature beat
      frequencies during the intervention weeks and no significant correlations were
      found between these variables and serum caffeine concentrations. CONCLUSIONS:
      Caffeine restriction has no role in the management of patients referred with
      symptomatic idiopathic ventricular premature beats.

PMID- 8983685
TI  - Effects of permanent dual chamber pacing on myocardial perfusion in symptomatic
      hypertrophic cardiomyopathy.
AB  - OBJECTIVE: Angina and the presence of myocardial ischaemia are common in
      hypertrophic cardiomyopathy. Dual chamber pacing results in clinical improvement
      in these patients. This study evaluates the effects of permanent dual chamber
      pacing on absolute regional myocardial perfusion and perfusion reserve. SETTING:
      University hospital. PATIENTS AND DESIGN: Six patients with hypertrophic
      cardiomyopathy and severe symptoms of angina received a dual chamber pacemaker.
      Absolute myocardial regional perfusion and perfusion reserve (dipyridamole 0.56
      mg/kg) were measured by dynamic positron emission tomography with 13N-ammonia
      both during sinus rhythm and 3 months after pacemaker insertion. Results were
      compared with those from 28 healthy volunteers. RESULTS: Pacing resulted in a
      reduction of anginal complaints and a reduction in intraventricular pressure
      gradient from 65 (SD 30) mm Hg to 19 (10) mm Hg. During sinus rhythm, baseline
      perfusion was higher in patients with hypertrophic cardiomyopathy than controls
      (184 (31) v 106 (26) ml/min/100 g, P < 0.01), and perfusion reserve was lower
      (1.6 (0.4) v 2.8 (1.0), P < 0.05). During pacing myocardial perfusion decreased
      to 130 (27) ml/min/100 g (P < 0.05), with variable responses in terms of
      perfusion reserve. Pacing caused a redistribution of myocardial stress perfusion
      and perfusion reserve. The coefficient of regional variation of myocardial stress
      perfusion decreased from 19.7 (7.0)% to 14.6 (3.9)% during pacing (12.9 (3.8)% in
      controls, P < 0.01). The coefficient of regional variation of perfusion reserve
      decreased from 16.7 (6.6)% to 11.4 (2.6)% during pacing (9.8 (4.1)% in controls,
      P < 0.01). CONCLUSIONS: Pacing caused a decrease of resting left ventricular
      myocardial blood flow and blood flow during pharmacologically induced coronary
      vasodilatation. Although global perfusion reserve remained unchanged, myocardial
      perfusion reserve became more homogeneously distributed.

PMID- 8983686
TI  - Pulmonary balloon valvuloplasty in the palliation of complex cyanotic congenital
      heart disease.
AB  - OBJECTIVE: To assess the value of pulmonary balloon valvuloplasty in the interim
      palliation of complex congenital heart disease and pulmonary stenosis in
      children, who often require numerous palliative operations before definitive
      surgical repair. METHODS: Evaluation of pulmonary balloon valvuloplasty
      procedures performed over a five year period in 18 patients (age 8 days--29
      years; mean 5.5 years) with complex cyanotic congenital heart disease. RESULTS:
      After pulmonary balloon valvuloplasty oxygen saturation increased from a mean
      (SD) of 69 (7.5)% to 83 (7.0)% (P < 0.001). Mean pulmonary artery pressure
      increased from a mean (SD) of 11.3 (3.8) mm Hg to 15.7 (3.9) mm Hg (P < 0.001).
      Transient complete atrioventricular block occurred in one patient. No other
      complications were encountered. In 5 patients (28%) there was an inadequate
      improvement in cyanosis compared with pre-procedure values (72 (4.7)% v 66
      (8.1)%). Reasons for failure were increasing infundibular stenosis in three and
      inadequate mixing in one child. In 13 patients (72%) pulmonary balloon
      valvuloplasty gave adequate interim palliation over a mean follow up of 1.1 (1.3)
      years. Oxygen saturation was 81 (5.6)% at last follow up compared with 70 (7.3)%
      before pulmonary balloon valvuloplasty (P < 0.001). CONCLUSION: Pulmonary balloon
      valvuloplasty is a safe and effective technique in the palliation of patients
      with complex cyanotic congenital heart disease associated with pulmonary valve
      stenosis.

PMID- 8983687
TI  - Intraoperative apical ventricular septal defect closure using a modified Rashkind
      double umbrella.
AB  - OBJECTIVE: To demonstrate the safety and efficacy of intraoperative apical
      ventricular septal defect (VSD) closure using a modified Rashkind double
      umbrella. DESIGN: Descriptive study of all patients in whom intraoperative device
      closure of apical VSDs was attempted. SETTING: A tertiary referral centre.
      PATIENTS: Four patients with an apical VSD requiring closure, during the period
      January 1993 to May 1995. INTERVENTIONS: Intraoperative placement of a modified
      Rashkind umbrella. RESULTS: Four successful placements resulting in apical VSD
      closure, as judged by transoesophageal colour flow mapping. Three patients
      received a 17 mm and one a 12 mm umbrella. Early complete closure was achieved in
      three patients. There was a small residual leak around the 12 mm device that had
      resolved at 5 month follow up. There was one early death, which was unrelated to
      VSD closure. CONCLUSION: Apical ventricular septal defects can be closed safely
      and effectively with intraoperative use of a modified Rashkind umbrella.

PMID- 8983688
TI  - Bacterial endocarditis involving a subaortic membrane.
AB  - A subaortic membrane predisposes to bacterial endocarditis usually affecting the
      aortic valve and left ventricular outflow tract. Endocarditis involving the
      subaortic membrane itself has been described twice only; once at operation and
      once at postmortem. The case of a man with vegetations involving a subaortic
      membrane that were detected preoperatively and the echocardiographic appearances
      of these findings are reported.

PMID- 8983689
TI  - Angina in McArdle's disease.
AB  - McArdle's disease (myophosphorylase deficiency) results in the inability to
      metabolise skeletal muscle glycogen to lactate. A patient with this condition
      developed angina and therefore offered a unique opportunity to explore the
      differential expression of the defective myophosphorylase gene in skeletal and
      cardiac muscle.

PMID- 8983690
TI  - A case of myocardial bridging: evaluation using intracoronary ultrasound, Doppler
      flow measurement, and quantitative coronary angiography.

PMID- 8983691
TI  - Hypereosinophilic syndrome: endomyocardial fibrosis.

PMID- 8983692
TI  - Gerbode's defect associated with acute sinus node dysfunction as a complication
      of infective endocarditis.

PMID- 8983694
TI  - [Surgical treatment of patients with complicated stomach and duodenal ulcer].

PMID- 8983695
TI  - [Retrospective analysis of errors in the diagnosis of acute appendicitis].

PMID- 8983693
TI  - Left ventricular non-compaction in a patient with becker's muscular dystrophy.

PMID- 8983696
TI  - [Surgical strategy in the treatment of complicated acute paraproctitis].

PMID- 8983697
TI  - [Prevention and elimination of blood circulation impairment in muscles after
      their microneurovascular transplantation].

PMID- 8983698
TI  - [Surgical treatment of morbid obesity].

PMID- 8983699
TI  - [New surgical scalpels with zirconium dioxide base].

PMID- 8983700
TI  - [Clinical and immunological bases of effectiveness of the use of endolymphatic
      therapy in the treatment of patients with pleural empyema].

PMID- 8983701
TI  - [Endoscopic laser surgery of tracheal tumors].

PMID- 8983702
TI  - [Clinical aspects, diagnosis and treatment of scar strictures of bile ducts].

PMID- 8983703
TI  - [Mathematical modeling of blood circulation in transplantation of tissue
      complexes on a single-component vascular pedicle].

PMID- 8983704
TI  - [Use of morphine after surgery of lower limbs under subarachnoid anesthesia].

PMID- 8983705
TI  - [Biomicroscopy of the iris in cancerous and precancerous diseases of the
      stomach].

PMID- 8983706
TI  - [Clinical bases of dynamics of adaptative reaction in children in the development
      of acute inflammation in the abdominal cavity. Possibilities of the concept
      "abdominal stress" in surgery].

PMID- 8983707
TI  - [Treatment of ureterohydronephrosis in duplication of upper urinary tract in
      children].

PMID- 8983708
TI  - [Significance of blood antigens in hematogenous osteomyelitis in children].

PMID- 8983709
TI  - [Endovascular interventions in decompensated liver cirrhosis].

PMID- 8983710
TI  - [New method of surgical treatment of pathologically movable kidney].

PMID- 8983711
TI  - [Laser surgery].

PMID- 8983712
TI  - [Use of low-invasiveness surgery in the treatment of cholelithiasis complicated
      by obstructive jaundice].

PMID- 8983713
TI  - [Peritoneo-anal resection with remucosation of the anal canal in the treatment of
      cancer of the middle ampullary section of the rectum].

PMID- 8983714
TI  - Joint meeting of the Association of Paediatric Anaesthetists of Great Britain and
      Ireland and the Belgian Association of Paediatric Anaesthetists.

PMID- 8983715
TI  - [Calcium, neuronal death and neurological disease].
AB  - Calcium ion (Ca2+) plays a role in several important functions in the central
      nervous system such as production of action potentials, neurotransmitter release,
      or neuronal plasticity, etc. However, its excessive influx to neurons due to
      failure of the mechanisms implicated in the regulation of its intracellular
      concentration (Ca(2+)-channels, calcium binding proteins), leads to a cascade of
      events which causes cytotoxicity and neuronal death. Ca2+ mediated toxicity has
      been implicated in the pathogenesis of neurodegenerative diseases (Parkinson's,
      Alzheimer's, amyotrophic lateral sclerosis, Huntington's), brain ischemia,
      epilepsy, cranial trauma, and AIDS-dementia complex. In this article we review
      the current status of this topic.

PMID- 8983716
TI  - [Schizophrenia: a psychobiological view].
AB  - Schizophrenia is a serious psychiatric illness which is responsible for a
      substantial proportion of mental illness worldwide. Symptoms include
      hallucinations, delusions, thought disorders (related with deficits of attention,
      memory and executive functions) and negative symptoms like poverty of thought and
      emotion, and social withdrawal. For most of this century the causes of
      schizophrenia have been largely unknown. However, the application of new
      techniques in genetics, structural and functional neuroimaging,
      psychopharmacology, epidemiology and neurochemical are beginning to disclose the
      aetiology of the disorder. Recent neurochemical data show that dysfunction of
      central dopamine systems may mediate symptoms in schizophrenia. Traditional
      antipsychotics are antagonists of dopamine D2-receptors, but some of the new
      atypical antipsychotics appear to have different action and drugs that interact
      with newly discovered dopamine and neuropeptides receptor subtypes of dopamine
      and neuropeptides are under investigation. In this sense, we review recent
      findings about interactions between opioid and dopaminergic systems with a
      special attention directed to cortical-striate-thalamic loops that could give new
      data about the aetiology and treatment of this serious mental illness. Finally,
      cognitive and attentional deficits in animal models of schizophrenia are
      reviewed.

PMID- 8983717
TI  - [Multiple sclerosis and quality of life].

PMID- 8983718
TI  - [Antiphospholipid antibodies and neurological disorders. Types and mechanisms].
AB  - The antiphospholipid antibodies (AAFL) are acquired antibodies of different types
      whose common characteristic is that they are directed against the negatively and
      neutrally charged phospholipids of the cell membranes. They were first described
      in 1952 in patients with systemic lupus erythematosus. They are also found in
      many pathological conditions such as: infections, solid and haematological
      neoplasms, chronic renal insufficiency, primary immunological deficiencies and
      other collagenoses, hepatobiliary diseases, etc. They are also found in other
      circumstances: due to the use of various drugs (which in general may induce
      lupus), in elderly patients and in apparently healthy people. The great interest
      shown in the past decade, as a result of their association with and possible
      etiopathogenic role in a series of thrombotic phenomena, neuropsychiatric
      disorders, thrombocytopenia and abortion-fetal death, has made them a major
      challenge to the clinician. This interest is increased by the controversial and
      very doubtful relationship that may exist with a series of disorders which have
      been described in detail. Their role as a probable risk factor for thrombosis in
      the general population is also discussed. For these reasons, we decided to review
      the basic biology of the AAFL and the aspects related to neurological disorders.

PMID- 8983719
TI  - [Study of electrocardiographic alterations during the acute phase of
      intracerebral hemorrhage and their prognostic implications].
AB  - The electrocardiographic abnormalities occurring with acute central nervous
      system disease were known phenomenon. In this study, we have done a descriptive
      study of 100 patients with intracranial haemorrhage (ICH) compared with a control
      group and the changes associated a worse prognostic. We have observed that the
      incidence of abnormalities electrocardiographic were most frequent in the
      patients with ICH (p < 0.05). The incidence of abnormalities in the pattern
      electrocardiographic was the 70% and the incidence of arrhythmias was the 56%. We
      have also observed that the presence of Q wave, QTc > or = 0.44 sec and the
      atrial fibrillations means a worse prognostic. We conclude that the incidence of
      abnormalities electrocardiographic in the ICH is elevate an the presence of Q
      wave, QTc > or = 0.44 an the atrial fibrillations means a worse prognostic.

PMID- 8983720
TI  - [Epileptic seizures during sleep].
AB  - Introduction. Epileptic crises presenting exclusively during sleep are rare and
      pose more problems of diagnosis than do crises of diurnal presentation. PATIENTS:
      We present the clinical and electroencephalographic data of 20 patients with
      exclusively sleep-induced epileptic crises, evaluating not only the type of
      crises and the diagnosis of the particular syndrome, but also the response to
      treatment and prognosis. The patients studied were over 17 years old, had only
      nocturnal crises and were followed up for a period of three years. An EEG done
      during sleep and cerebral CT scan were available in all cases and a cranial MR
      was available in two cases. Diagnosis was made using clinical data and the sleep
      EEG. RESULTS: The majority (40%) had temporal lobe epilepsy. In two patients
      (10%) occipital paroxysms were found. In all cases both the neurological
      examination and the mental state were normal. The sleep EEG was pathological in
      75% of the cases. Only three of the twenty patients had changes on the CT scan.
      Monotherapeutic antiepileptic treatment completely controlled the crises in 15
      patients. CONCLUSIONS: We wish to emphasize the usefulness and importance of the
      sleep EEG in defining the syndrome affecting these patients, the diagnostic
      difficulties in sleep epilepsy, the good response to antiepileptic treatment and
      the high incidence of recurrence if antiepileptic treatment is no longer given.
      In view of all these factors we believe that sleep epilepsy may be considered to
      be a syndrome of epilepsy.

PMID- 8983721
TI  - [Magnetic resonance imaging usefulness in the diagnosis of intratumor bleeding in
      hypophyseal adenomas].
AB  - Hypophyseal adenomas are the most frequent intrasella tumours. They are
      classified as macroadenomas or as microadenomas depending on whether their size
      is greater or less than 1 cm. Hypophyseal tumours may undergo ischaemic necrosis
      and haemorrhage when the blood supply is reduced. Intratumoural bleeding is found
      in varying percentages, between 9.9% and 26%. We review our series of 122
      patients with hypophyseal adenomas in whom MR was done. Signs of bleeding were
      found in 12 patients (9%). In five cases, bleeding had presented as hypophyseal
      apoplexy, in five cases with subacute symptoms and in two cases was asymptomatic
      and diagnosis fortuitous. Of the adenomas with intratumoural bleeding, 9 were
      functioning tumours (4 secreted PRL, 4 ACTH and 1 GH) and 3 non-functioning. The
      risk factors considered in the pathogenesis of intratumoural bleeding are
      numerous. The increased incidence of bleeding in large and in invasisve adenomas,
      especially when treated with bromocriptin, is well established. MR is the ideal
      technique to detect intratumoural bleeding, T2 weighted sequences being very
      useful in the diagnosis of bleeding in the acute phase. In the subacute phase,
      focal areas of hyperintensity are seen in T1 and of hypo/hyperintensity in T2. In
      the chronic phase, areas of hypodensity are seen both in T1 and in T2. In our
      study we analyze the clinico-radiological correlation in patients with signs of
      intratumoural bleeding.

PMID- 8983722
TI  - [Platybasia, basilar groove, odontoid process and kinking of the brainstem: a
      common etiology with idiopathic syringomyelia, scoliosis and Chiari
      malformations].
AB  - INTRODUCTION: A common aetiopathogenic theory for basilar groove (IMB),
      platybasia (PTB), odontoid retrocession (RTO), kinking of the brainstem (KTC)
      applied to idiopathic syringomyelia (SMI), idiopathic scoliosis (ESCID) and
      Arnold-Chiari malformation (ARCH) is presented. Confirmation is based on an
      abnormally low position of the conus medullaris (CMB) in the patients with SMI.
      MATERIALS AND METHOD: 292 patients with syringomyelia (SM), 231 with SMI were
      selected. Of these, 55 were chosen who had SMI and in whom the level of the conus
      medullaris (NCM) could be determined, together with the figures for SMI, IMB,
      PTB, RTO, KTC, ESCID and ARCH on cervical and lumbar MR. The position of the
      conus medullaris in 50 patients who did not have SM, ESCID nor ARCH on cervical
      and lumbar RM was determined. RESULTS: 32 patients had an increased basal angle
      (58.18%). There was an IMB in a quarter of the patients (25.45%). RTO was
      observed in half of the patients (47.27%). Just over one third presented a KTC.
      6% of the control group had CM at the level of the body of L1, whilst 84.21% of
      the patients with SMI presented a partial or complete CM image at this level.
      CONCLUSIONS: CMB in SMIU and its close relationship with IMB, PTB, RTO AND KTC
      and also with ESCID and ARCH make it likely that they share the same
      aetiopathogenic mechanism: an abnormal lack of synchronization of the growth of
      the neuro-axis and the neural canal (AACNN), causing a specific disorder which is
      seen as different syndromes.

PMID- 8983723
TI  - [Analysis of the block design test in a geriatric sample group].
AB  - We have carried out a study to determine the normal values of the 'block design
      test' in a sample group of 58 healthy elderly persons, a test which is usually
      used in the clinical evaluation of constructive apraxia. We therefore describe a
      grading scale which has not been previously published, in order to check the
      possible usefulness of this drawing as a rapid test of cognitive evaluation. A
      study was made of the possible interaction of the test with sample parameters,
      age, sex, educational level and also the inter-examiner reliability. We have
      observed a significant interaction between the variables of sex and educational
      level. Also the inter-examiner reliability is not very good. In view of our
      results, we consider that the 'block design test' is not very useful in the
      evaluation of constructive praxis in healthy elderly persons, and therefore it
      does not seem to us to be a good test for the rapid evaluation of cognitive
      function in this group.

PMID- 8983724
TI  - [Treatment of refractory infantile epilepsy with vigabatrin in a series of 55
      patients].
AB  - We present the results of treatment with vigabatrin in the polytherapy of
      resistant infantile epilepsy. A retrospective review of 55 children with
      resistant epilepsy aged between 2 months and 15 years was carried out between
      January 1992 and January 1995. Semiologically, the crises treated were simple
      partial crises (CPS), complex partial crises (CPC), West's syndrome, the Lennox
      Gastaut syndrome and polymorphic crises. The efficacy of the drug (defined as a
      50% or more reduction in crises), secondary effects and the reduction in the
      number of drugs necessary were evaluated. 60% of the children studied improved.
      20% became completely free of crises. 34% remained unchanged and 3% became worse.
      In West's syndrome 100% responded satisfactorily, as did 80% of the cases of
      partial crises, but only 40% of those with Lennox's syndrome responded.
      Generalized tonic-clonic crises did not respond, and myoclonic crises became
      worse. Aetiologically, there was greater improvement in the symptomic cases than
      in the essential cases, the improvement being 70% while 5 patients with tuberose
      sclerosis responded particularly well. Medication was stopped in one case because
      of side-effects, due to a psychiatric disturbance, and in another case vigabatrin
      caused transitory side-effects. In 10% of the subjects the initial efficacy wore
      off around 6 months later. We have shown the usefulness of vigabatrin in the
      polytherapy of infantile epilepsy, which is resistant to conventional epileptic
      drugs, mainly in simple and complex partial crises and in West's syndrome. Its
      minimal side-effects and the favourable response in over 50% of cases make it an
      extremely useful drug.

PMID- 8983725
TI  - [Neonatal convulsions in health care. I. Incidence, etiology and clinical
      aspects].
AB  - OBJECTIVE: To determine the incidence, etiology and course of neonatal
      convulsions in the Albacete Health District between 1991 and 1993. DESIGN: A
      descriptive study of retrospective cohorts. SCOPE: 12,427 new born babies in the
      province of Albacete. The Hospital General de Albacete looks after a population
      of 376,071 inhabitants, attends 82% of the births in this area and its
      Neonatology Department is the only one in the province. METHOD: Incidence: we
      found 25 new born babies (RN) with neonatal convulsions: absolute incidence (IA)
      in live RN0/00.; IA in live full-term RN (RNI) 1.4(0/00); IA in preterm RN (RNPT)
      13.4(0/00) and in immature RN (with a gestational age of < 29 weeks) 27.8(0/00).
      ETIOLOGY: hypoxic-ischaemic encephalopathy 32%, malformations or cerebral
      dysgenesis 24%, intracranial hemorrhage 16%, with less frequency: infections,
      metabolic and pharmacological changes 8%, epileptogenic diagnosis 4%. COURSE: 10
      of the RN (40%) died, 8 (32%) had sequelae, although in 3 cases these were
      transient, and 7 had developed normally (28%). Other relevant aspects are
      described: neurological findings between crises, type of crisis, EEG and
      neuroimaging techniques. DISCUSSION: We attribute the poor prognosis of our
      series, as compared to other published series, to an increase in the incidence of
      convulsions associated with a worse prognosis (RN with antepartum fetal distress,
      cerebral malformations and metabolic encephalopathies), and a decrease in acute
      intercurrent conditions; hypoglucemia, hipocalcemia and hypothermia, which do not
      leave sequelae after treatment. Also when methods of clinical inclusion/EEG are
      used, evaluating only the epileptic phenomena, convulsive crises with minimal
      clinical signs are observed.

PMID- 8983726
TI  - [Evolutive neuroradiological alterations in Sandhoff's disease].
AB  - Sandhoff's disease is a severe form of gangliosidosis GM2 which presents in the
      first year of life, basically as progressive psychomotor retardation and/or a
      macular red cherry spot. Our patient presented the clinical picture
      characteristic of the disease. Diagnosis was confirmed by determining the
      activity of hexosaminidases A and B in serum and of beta-N-acetil hexosaminases
      in fibroblast culture. In view of the fatal prognosis of the disease, in 1991 a
      transplant of alogenic bone marrow (TMO) was carried out to try to replace the
      enzymes. This required exhaustive radiological follow-up to determine the
      possible neuro-radiological changes seen in this storage disease. Although
      treatment was not successful, the neuro-radiological findings may be of interest
      as perhaps being characteristic of the GM2 gangliosidosis: 1. Bilateral thalamic
      hyperecogenity in the cerebral ecography. 2. Differences between the thalamo
      putamen densities due to bilateral homogeneous thalamic hyperdensity on the CT
      scan. 3. Thalamic hypointensity both on T2 sequences and in proton density on MR
      with the cerebral white matter being progressively affected. In conclusion, we
      suggest that bilateral symmetrical thalamic changes are an early finding which is
      probably specific to the GM2 gangliosidoses and may be useful from the point of
      view of carrying out more specific investigations in infants suspected of having
      a degenerative neurological disorder.

PMID- 8983727
TI  - [Cranioencephalic cutaneous angiofibromatosis].
AB  - A nine year old girl with no significant prenatal or perinatal history had
      presented, at the age of four months, with infantile spasms and later with
      partial crises with or without secondary generalization. On examination there was
      left hemiparesis and various skin lesions: a pink plaque in the frontal region
      with hair loss, fibrous plaques on the right side of the face and hypomelanic
      spots on the trunk and thighs and some cafe-au-lait spots on the thorax and
      abdomen. On neuroimaging by CT and MR right cerebral hemiatrophy, periventricular
      calcifications and lesions in the right hemisphere were seen. On AMR an angioma
      was seen on the anterior communicating artery. A skin biopsy of the frontal
      plaque showed perifollicular fibromatosis with marked vascular proliferation. We
      discuss whether the presentation of this case of encephalocraneo-cutaneous
      angiofibromatosis is a new phenotype of tuberose sclerosis or a new
      neurocutaneous syndrome.

PMID- 8983728
TI  - [Pyruvate dehydrogenase deficiency and cerebral malformations].
AB  - Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic
      acidosis and severe global developmental delay. A deficiency of PDH E1 alpha, a
      subunit of the PDH complex is a prominent cause of congenital lactic acidosis.
      The E1 alpha cDNA and corresponding genomic DNA have been located in the short
      arm of the X-chromosome (Xp22-1). A isolated 'cerebral' lactic acidosis with
      cerebral dysgenesis is a recognized pattern of presentation of PDH deficiency.
      Here, we report clinical features, magnetic resonance, and biochemical studies of
      two females aged 6 months (case 1) and 26 months (case 2). Both had severe
      development delay, minor dysmorphic features, microcephaly, severe hypoplasia of
      the corpus callosum, cerebral atrophy, ventricular dilatation and increase in
      serum lactate levels without systemic acidosis. Urinary organic acid profile was
      compatible with PDH deficiency. Increased CSF lactate and pyruvate levels and
      reduced total PDH and PDH E1 activities in muscle and fibroblasts were observed
      in case 1. Otherwise, decreased total PDH activity in muscle but not in
      fibroblasts was seen in case 2. The PDH E1a gene was sequenced in the case 1 and
      a deletion in exon 7 was demonstrated. Dysmorphism with severe cerebral
      malformations in female patients merits a metabolic evaluation, including
      determination of lactate and pyruvate levels in CSF.

PMID- 8983729
TI  - [Neurological presentation of systemic lupus erythematosus].
AB  - We describe the case of a 61 years-old-woman with lupus erythematosus who
      presented with neurological symptoms, namely dementia, focality and crisis. The
      neurological presentation of lupus is evaluated clinically, being similar to the
      central manifestations of patients with systemic onset. The marked cognitive
      affectation with relation to other cases of lupus with a neurological onset is
      emphasized. MR has been shown to be a sensitive means of detection of
      corticosubcortical lesions of neurolupus, not specific to this condition, as well
      as to their response to immunosuppressors. The aetiopathogenesis of some of the
      manifestations of cerebral lupus and the clinical response to corticosteroids and
      cyclophosphamide is reviewed.

PMID- 8983730
TI  - [Muscular spasms associated with a reflex sympathetic dystrophy].
AB  - The appearance of involuntary movements in the clinical course of reflex
      sympathetic dystrophy (DSR) constitutes a rare clinical entity. In this context,
      the most frequent changes in movements are muscle spasms and focal dystonia,
      although postural tremor, muscle weakness and rhythmic myoclonus have also been
      described. The disorder is more frequent in young women and in the lower limbs.
      It may have a focal, segmental, multifocal, hemicorporal or symmetrical
      distribution. It is almost always secondary to local trauma. The pathogenesis and
      most effective treatment are unknown. We present the case of a 62 year old woman
      with muscle spasms of both legs and feet as a complication of spontaneously
      appearing DSR. The electromyogram showed continuous non-rhythmic discharges with
      morphologically normal motor unit potentials in both anterior tibial muscles. The
      clinical course and symptomatic improvement following treatment with
      benzodiazepine seems to suggest that the disorder is of central origin.

PMID- 8983731
TI  - [Post-traumatic tics].
AB  - Secondary tics are those in which an aetiology justifying them can be found, as
      compared to idiopathic tics, which make up the majority, and the Gilles de la
      Tourette syndrome (SGT), which is, at the moment, of unknown origin. Of the
      possible aetiologies described as causing tics, craneo-encephalic trauma has been
      mentioned on very few occasions. We present a case of post-traumatic tics (verbal
      and neck) in a young man of 24, and review the published cases which can be
      considered to be of post-traumatic tics. We have found six cases of tics
      secondary to traumas, all craneo-encephalic, like ours (the one under study). The
      time interval between the blow and the appearance of the tic or tics varied
      between 2 weeks and 3 months. The absence of significant lesions seen in the
      complementary investigations make it impossible for us to discover the site of
      the lesion caused by the trauma. However, the presence in some cases of other
      tics before the trauma, and of family histories of tics, supports the idea of a
      genetic basis or predisposition to suffer this disorder.

PMID- 8983732
TI  - [The 1906 neurological meeting in Tubingen and the first Alzheimer's disease
      case. A critical study].

PMID- 8983733
TI  - [Primary cerebral lymphoma: atypical image].

PMID- 8983734
TI  - [Trigeminal evoked potentials through the glossal nerve in normals. A preliminary
      study. Letter].

PMID- 8983735
TI  - [Fibromyalgia in right half of the body as the onset of mitochondrial cytopathy.
      Letter].

PMID- 8983736
TI  - [Parkinson's syndrome as presentation form of left fronto-parietal meningioma.
      Letter].

PMID- 8983737
TI  - [Pseudotumor cerebri caused by vitamin excess due to intake of milk enriched with
      A and D vitamins. Letter].

PMID- 8983738
TI  - [Brain miliary metastases secondary to a renal adenocarcinoma].

PMID- 8983739
TI  - [The tolerance of two therapeutic uses of triflusal in patients with ischemic
      stroke. Letter].

PMID- 8983740
TI  - [Scientific publications in Spanish].

PMID- 8983741
TI  - [The number of neurological publications in Spain].

PMID- 8983742
TI  - [The therapeutic and therapeutic-prophylactic action of pectins].

PMID- 8983743
TI  - [Immune disorders in osteoarthrosis in miners].
AB  - An immunologic evaluation was done in healthy miners and those working in coal
      mines suffering from deforming osteoarthrosis. Blood levels of beta 2
      microglobulin and circulating immune complexes, titres of antibodies to
      glycosaminoglycans and antigens from cartilaginous tissue and synovial membrane
      were all found to be elevated. Shifts in the immunity system were clearly related
      to the spread of the pathological process as well as the rate of the disease
      progression and presence of reactive synovitis but not with occupation of the
      patients. Clinico-immunologic manifestations of osteoarthrosis were unfavourably
      influenced by industrial mining-geological factors.

PMID- 8983744
TI  - [The anti-immunodepressive action of kumiss made from cow's milk].
AB  - Data are submitted from the experimental study of anti-immunodepressive effects
      of koumiss from cow milk. Koumiss as a feed supplement for white mice and
      chickens was found out to make for a notable increase in the number of animal
      specimens exhibiting a strong immune response to the antigens they had been
      previously immunized with. The immunostimulating effect was pronounced as well in
      those animals having previously received massive doses of prednizolone.

PMID- 8983745
TI  - [The possible hypolipidemic action of the dietary fiber from barley meal].
AB  - A possible hypocholesteremic property was studied of food fibers from barley in a
      subchronic experiment on 60 white nondescript male rats under developing
      hypercholesterolemia of alimentary genesis. An aggravated dose of the above
      fibers has been shown to reduce deviations from the reference level brought about
      by administration of exogenous cholesterin. On completing the clinical trials,
      the studied product may be used in nourishment of those individuals presenting
      with disordered lipid metabolism.

PMID- 8983746
TI  - [Lipid peroxidation and the antioxidant activity of the blood serum in diabetic
      patients].

PMID- 8983747
TI  - [An improved classification of chronic heart failure].
AB  - A clinicofunctional classification is proposed of chronic cardiac insufficiency
      (ChCI), based on the modified classification by Strazhesko-Vasilenko on the
      syndrome type and New York Association of Cardiologists. Each of the clinically
      important functional classes is subdivided into subclasses. Clinically manifest
      ChCI is subdivided into reversible, partly reversible and irreversible
      subclasses.

PMID- 8983748
TI  - [The reaction of the sympathoadrenal system to an acute peroral salt load in
      young persons with arterial hypertension].
AB  - 73 young persons 15 to 30 years old with normal and elevated arterial pressure
      were studied for excretion of epinephrine, norepinephrine and dophamine during 3
      and 24 hours after acute peroral salt loading (0.22 g/l kg of body mass). The
      study was made with special reference to the family prevalence of hypertensive
      disease. Healthy subjects demonstrated an increased excretion of dopamine and
      decreased excretion of norepinephrine after the test. Those persons with arterial
      hypertension showed disordered reaction of the sympathoadrenal system to the salt
      loading. Functional mechanisms of hereditary predisposition to this medical
      condition involve a decreased excretion of dophamine in the first three hours and
      increased excretion of epinephrine within the 24 hours after the test.

PMID- 8983749
TI  - [Nifedipine in the treatment of arterial hypertension in patients with the
      neuroendocrine-metabolic form of the hypothalamic syndrome].
AB  - The authors submit results of treatment of 30 patients presenting with
      neuroendocrine-metabolic form of hypothalamic syndrome with a 3-months course
      administration of nifedipine on a 30-mg daily schedule. Before the treatment, the
      patients had persistent arterial hypertension and abnormal values for central
      hemodynamics presenting as hypokinetic syndrome. After the treatment with
      corinfar, the patients fared significantly better, with the arterial pressure and
      index of the general peripheral vascular resistance getting down. Values for
      minute volume, stroke volume, cardiac index tended towards normalization.

PMID- 8983750
TI  - [The classification of chronic pleurisy and the limits of its conservative
      treatment].
AB  - The author focuses on the pathoanatomical and pathophysiological aspects of
      chronic pleuritis, ways of formation of chronic pulmonary heart. The clinico
      roentgenologic classification proposed by the author suggests limits to the
      conservative treatment of pleuritis together with the indications for surgical
      intervention preventing the above complication. Using the criteria of the
      author's classification, there have been carried out a total of 211 surgical
      interventions; of these, 203 were pleurectomies. All patients were discharged
      from hospital in adequate condition.

PMID- 8983751
TI  - [The link between the prognostic factors in acute leukemia and patient age].
AB  - A total of 464 case records of those patients with acute leukosis 15 to 80 years
      old have been analysed. Age was found to have unfavourable potential for
      achieving complete remission as well as length of life of the patients. Other
      parameters of prognostic significance for the course of acute leukosis
      (cellularity of bone marrow, enlargement of peripheral lymph nodes, percentage of
      blast cells in haemogramme and myelogramme, thrombocytopenia) were not recognized
      to be directly age-associated. Age appeared to correlate significantly with
      infectious complications, pneumonia, as an immediate cause of death of the
      patients.

PMID- 8983752
TI  - [Experience in the combined treatment using ciprofloxacin of urethrogenic
      prostatitis].

PMID- 8983753
TI  - [The effect of diltiazem on systemic and cerebral hemodynamics and on the blood
      rheological properties in patients with ischemic stroke and atherosclerotic
      involvement of the major cerebral arteries].
AB  - Overall thirty-five patients with ischemic insult against the background of
      occlusive lesions of major arteries of the head were evaluated for effects of
      cardil on systemic and cerebral hemodynamics and rheologic properties of blood.
      It has been shown that cardil increases significantly cerebral bloodflow
      predominantly on the side of the stenosis, does not cause intracerebral
      "stealing" in the acute phase of insult, improves bloodflow to the brain and
      collateral blood supply in the residual phase due to selectivity of its influence
      on cerebral vessels, lowers arterial pressure, decreases frequency of
      contractions, as well as cardial and stroke indices, and volume of circulating
      blood. The drug suppresses aggregatory properties of thrombocytes and
      erythrocytes during different stages of ischemic insult, and makes blood
      viscosity somewhat less.

PMID- 8983754
TI  - [The treatment of gonarthrosis by local vacuum compression in combination with
      carbon dioxide (a clinical and rheovasothermmal assessment)].

PMID- 8983755
TI  - [Treatment of the reflex syndromes of lumbar osteochondrosis at a central
      district hospital].
AB  - Experience is reported of treatment of patients presenting with reflex lumbar
      osteochondrosis syndromes (n = 136) by manual therapy and acupuncture. The
      majority of patients derived apparent benefit from the treatment (n = 102),
      twenty-six in this patient population showed improvement, 8--no effect. Manual
      and acupuncture treatments allowed to shorten the time during which patients
      presenting with the above pathologies are incapacitated from working. Methods of
      sum and stimulant electroneuromyography constitute a useful addition to clinical
      findings permitting an objective assessment to be provided of the effectiveness
      of treatment of patients presenting with reflex syndromes of lumbar
      osteochondrosis.

PMID- 8983756
TI  - [The efficacy of caleflone in treating patients with viral hepatitis].
AB  - Effects were studied of caleflone on the course of viral hepatitis A and B in 94
      patients presenting with moderately severe form of the condition. The drug was
      found to have a positive effect on the course of the illness. In the patients
      examined, inhibitory action of caleflone on lipid peroxidation was revealed.
      Caleflone is recommended for use in a combined treatment of patients with viral
      hepatitis A and B.

PMID- 8983757
TI  - [Decimeter-wave physiotherapy in viral hepatitis].
AB  - Effectiveness was evaluated of magnetotherapy, inductothermy, UNF electric field
      and electromagnetic waves of decimetric wave band (460 MHz) on the projection of
      the liver, adrenals and thyroid gland in controlled trials enrolling a total of
      835 patients with viral hepatitis (type A, B, associated forms). A conclusion is
      reached that optimum effectiveness of decimetric field on the projection of the
      adrenals and thyroid gland can be achieved through the application of minimum
      power and everyday alternation of exposures. It has been estimated that as many
      as 69 percent of the patients derive benefit from the above treatment.

PMID- 8983758
TI  - [The clinical picture and treatment of diphtheria in adults].

PMID- 8983759
TI  - [Diphtheria in Ukraine. The current aspects of diphtheria epidemiology (1)].
AB  - From 1991 forth, a diphtheria epidemics has been spreading in Ukraine, the cause
      of which is decline in the level of collective immunity. The highest incidence
      rates are registered in large industrial centers. In rural areas, morbidity rates
      were found to be half as high as those in urban ones, particularly so among the
      adults. Morbidity and mortality were greater among those children of under school
      age who did not attend the child's pre-school institutions. Immunization of the
      adults done on a single-procedure basis does not protect them either against the
      disease or lethal outcome. The observed decline in mortality is due to the
      detection of mild forms of the disease, earlier diagnose and, therefore, start of
      the treatment. But even in 1994 the epidemic situation with respect to diphtheria
      looks serious in Ukraine, which fact necessitates inaugurating antiepidemic
      measures on a continuous basis, the mainstay of which is vaccinal prevention.

PMID- 8983760
TI  - [Diphtheria among adults in Ukraine].

PMID- 8983761
TI  - [The use of Intetrix in acute diarrheal diseases].
AB  - The authors used intetrix (of 'Bofur-Ibsen' production) to treat patients with
      bacterial dysentery, escherichiosis, intestinal form klebsiellosis and cholera.
      There has been demonstrated marked therapeutic effectiveness of the preparation,
      particularly when used in combination with smecta.

PMID- 8983762
TI  - [Experience in using extracorporeal detoxication in the intensive therapy of
      autoimmune pathology].
AB  - The author submits results of treatment of patients with various autoimmune
      pathologies. Intensive care therapy of the above patients involving sorption
      detoxication and separation plasmapheresis were shown to allow definite reduction
      in blood concentrations of different type metabolites, which fact permits
      enhancing efficiency of treatment of patients presenting with scalded skin
      syndrome, Raynaud's disease, myasthenia and chronic pyelonephritis.

PMID- 8983763
TI  - [The treatment of vibration-induced disease with calcium-channel blockers].
AB  - Effectiveness was studied of two drug preparations of calcium antagonists CAs
      group: cordaphene (30 mg) and diltiazeme (180 mg) in patients with vibration
      disease (VD) due to local vibration. CAs were shown to exert peripheral
      vasodilating, membrane-protecting and antioxidant effects. Cordaphene appeared to
      have a most pronounced CAs effect. We should advise its prescription preferably
      in those VD patients presenting with concomitant arterial hypertension.

PMID- 8983764
TI  - [The etiology of aplastic anemia].

PMID- 8983765
TI  - [The effect of mercazolyl on the activity of the main hemostatic blood systems
      under the action of immobilization stress].
AB  - In the animal experiments (rabbits), a reaction was studied of lysosomal
      apparatus of the peripheral blood and haemostatic system neutrophilic leucocytes
      in response to exposure to immobilization stress under depression of thyroid
      system caused by administration of mercazolilum. Thyroid hormones were
      ascertained to play their part in regulation of functional activity of Hageman
      dependent systems of blood via activation of lysosomal apparatus of neutrophilic
      leucocytes of the rabbits' blood.

PMID- 8983766
TI  - [The effect of vitamins on the natural body resistance of patients with malignant
      lymphomas].

PMID- 8983767
TI  - [The effect of different morphological forms of kidney cancer on body temperature
      reaction].

PMID- 8983768
TI  - [Cardiac involvement in Reiter's disease].
AB  - The present article discusses modern concepts on possible instances of
      cardiovascular involvement in Reiter's disease during the early and late stages
      of this medical condition. A case is reported in a clinical setting of left
      ventricular dilatation development and complicated life-threatening arrhythmia in
      a patient presenting with Reiter's disease.

PMID- 8983769
TI  - [A fatal case of chronic Q fever with cardiovascular involvement].
AB  - A lethal case is reported of chronic Q-fever in a patient aged 34 who regarded
      himself as completely healthy six months before his death. The diagnosis was made
      on the basis of vital investigation of blood sera in a complement-fixation test
      and indirect fluorescent-antibody test (antibody titers 1 : 1280 against phase 1
      and 1 : 320 against phase 2 Coxiella burnetii), differentiation of antibodies as
      distinct classes of immunoglobulins, results of pathoanatomical and
      microbiological investigations. Pathoanatomical features of the organs are fully
      detailed, especially those of the heart. Death occurred in the presence of
      cardiac failure growing progressively worse, involving many organs. Patients with
      cardiovascular pathology have to be examined for Q-fever in order that we should
      be able to early detect and apply specific therapy to treat its chronic form.

PMID- 8983770
TI  - [Pylephlebitis as a preoperative complication of acute appendicitis].

PMID- 8983771
TI  - [The efficacy of metabolic therapy in chronic gastritis with secretory deficiency
      in flight personnel].
AB  - Overall ninety individuals (all males) of flying personnel 22 to 45 years old
      were examined under inpatient medical care facility conditions. Diagnosis of
      chronic gastritis (ChG) was confirmed with the aid of fibrogastroduodenoscopy,
      histologic, histochemical (periodic acid-Schiff reaction) sections of aimed
      biopsy specimens of gastric mucosa (GM), as well as by the use of euphyllinum,
      histamine while studying gastric secretion. Distinguishing features were noted of
      the ChG course as were their relatedness to the aircrew activity. On completing
      the metabolic therapy involving use of calcium gluconate, euphylline, panangine,
      24 ChG patients presenting with secretory deficiency enjoyed clinical, metabolic,
      acid-producing effect superior to that of replacement therapy.

PMID- 8983772
TI  - [The prevention of hemorrhoids in sailors].
AB  - Seafaring personnel are exposed in their everyday life and work to factors of
      ship environment contributing to the development of hypomotor intestinal
      dyskinesias, colitis, proctitis, proctosigmoiditis, hemorrhoids. Rations for
      seafaring personnel are deficient in food fibre: 11 g per twenty-four hours, with
      the norm being 40-70 g per twenty-four hours. A positive result was achieved in
      the study of the action of a concentrate of food fibre prepared from wheat bran
      by special methods in patients with hemorrhoids. The above concentrate can be
      recommended for prevention and dietotherapy of hemorrhoidal disorders of the
      intestine and hemorrhoids.

PMID- 8983773
TI  - [New forms of the disability list and the problems of studying morbidity].

PMID- 8983774
TI  - [The disability of patients with hypertension as a social hygiene problem].

PMID- 8983775
TI  - [Diagnosis and the International Statistical Classification of Diseases, Injuries
      and Causes of Death].
AB  - International Statistical Classification of Diseases, Traumata and Causes of
      Death does not regulate the wording of diagnosis in the medical history, protocol
      of a post mortem examination, or even medical certificate of cause of death. The
      only thing that is required in the latter is putting the pathogenetic sequence in
      reverse order and indicating in point Ia the certificate of illness or
      complication rather than functional diagnosis essential for the work of encoders.
      Therefore it is not and has never been necessary to fit formulations of diagnoses
      and features of statistical statements together and there is no need for
      introduction into the diagnosis of the International Classification of Diseases
      the generalizing terms either. It is physicians-statisticians that are to be
      concerned with encoding of diagnoses, know all fine points, all the ins and outs
      of the statistical statement of such-and-such diseases and conditions.

PMID- 8983776
TI  - [Means for further improvement in the activities of hospital consultation
      committees as support systems for the management of the quality of medical care
      (based on data from Kiev)].

PMID- 8983777
TI  - [The activities of physicians and scientists from Odessa, Kiev and Kharkov in
      foreign universities].

PMID- 8983778
TI  - [The history of the origin and development of the ideas of cybernetics in the
      works of medical scientists and biologists of Ukraine and Russia].

PMID- 8983779
TI  - [The ecological-hygienic aspects of the study of industrial-frequency magnetic
      fields].
AB  - Magnetic fields of industrial frequency with magnetic flux density of 10 mkTl
      were studied for their effects on the morbidity pattern in the population of the
      settlement located in the vicinity of a high-voltage electric power line of 750
      kV. A trend was noted towards increase in the incidence of nervous and endocrine
      diseases as well as metabolic disturbances and disorders of the immune system.

PMID- 8983780
TI  - [Current treatment approaches and prospects in thyroid cancer].
AB  - A comparative analysis is presented of surgical treatment of 603 patients with
      malignant tumors of the thyroid gland before and after the Chernobyl NPP
      accident. Pediatric patients showed higher aggressiveness of the struma maligna
      course in the post-accident period, which fact suggests the need for broadening
      indications for thyroidectomy with radical intervention on regional lymph
      collectors.

PMID- 8983781
TI  - [Latent thyroid cancer in the inhabitants of Kiev (based on autopsy study data)].
AB  - Thyroid glands obtained in post mortem examination of Kievites over the period of
      1993 to 1994 were serially sectioned and subjected to pathomorphologic
      investigation that disclosed latent pathologic changes in 40.7 percent of the 162
      cases, with struma maligna having been identified in 11.7 percent. This is
      significantly higher the currently known estimates of struma maligna morbidity
      rates, which fact suggests the need for devoting greater amount of time and
      effort to the thyroid abnormalities in the resident population of this region.

PMID- 8983783
TI  - [The risk factors for sudden coronary death in patients with unstable angina].

PMID- 8983782
TI  - [The transformation of psoriasis into mycosis fungoides in a person who worked to
      cleanup the aftermath of the accident at the Chernobyl Atomic Electric Power
      Station].

PMID- 8983784
TI  - [The structural-functional status of the myocardium and central and regional
      hemodynamics in patients with essential hypertension under the influence of
      treatment with korinfar and its combination with anaprilin].

PMID- 8983785
TI  - [Cellular and humoral immunity indices in patients with myocardial infarct
      complicated by thromboendocarditis].
AB  - Data are submitted on the time course of immunologic indices in 50 patients with
      myocardial infarction (MI) presenting with complication-free course, and 58
      patients with MI complicated by thromboendocarditis. Important changes were
      revealed in the immune status--both cellular and humoral--during the development
      of thrombosis of the left ventricle secondary to MI. The cellular immunity was
      characterized by a decline in the levels of T-lymphocytes, particularly those of
      T-suppressors, augmentation of B-lymphocytes. Thrombosis evolving in MI was
      associated with changes in humoral immunity, such as persistent and lasting rise
      in immunoglobulins of all classes, especially Ig G, as well as combinations
      thereof, together with the increase in the content of circulating immune
      complexes.

PMID- 8983786
TI  - [The role of free-radical processes in determining immune disorders in unstable
      angina and the principles for their correction].
AB  - The interaction was studied of homeostatic lipids of the membrane components in
      the blood plasma as was the correction thereof and condition of the bodily immune
      processes in patients with unstable angina pectoris (UAP). A total of fifty UAP
      patients were treated with lipid. Utilization of the lipid modulus was found out
      to have a striking immunoregulation effect. Activation of the phagocytic link of
      the immune response was noted to be on the decrease, the disbalance of the
      regulatory lymphocyte subpopulations getting less, which facts result in lowering
      of the autoantibodies production, normalization of blood free radical processes
      and pronounced clinical effect in the above patient population.

PMID- 8983787
TI  - [The incidence and characteristics of the clinical picture of recurrent
      myocardial infarct in the rural population].
AB  - As many as 3033 patients with myocardial infarction residing in rural areas were
      kept under observation. In this population, myocardial reinfarction (MRI) was
      diagnosed in 411 subjects, with 78.8% having had it for 4 years. Those MRI
      patients ranging between 51 to 60 years showed the greatest prevalence (44.3%).
      The ratio of micro- to macrofocal (through-and-through) MRI was 1:3, that of
      males to females 9:1. Microfocal MRI was commonly associated with a pain-free
      variant of the disease (23.5%) with low frequency of thromboembolic complications
      (3.1%). Every fifth patient with macrofocal (through-and-through) renecrosis
      presented with aneurysm of the heart. In a 10-year and longer follow-up,
      mortality from MRI was 43.6 percent among patients with macrofocal MRI, while
      deaths attributable to microfocal MRI were estimated to be 28.9 percent. High
      mortality rates suggest great severity of illness and low efficacy of the drug
      therapy adopted.

PMID- 8983789
TI  - [The characteristics of the use of ursodeoxycholic acid in chronic diseases of
      the hepatobiliary system].

PMID- 8983790
TI  - [The pathogenetic role of dysbacteriosis of the large intestine in the recurrence
      of peptic ulcer].
AB  - Microbiologic investigations were carried out of excrements as were measurements
      of blood levels of malonic dialdegyde, reduced glutathione and activity of
      glutathione-dependent enzymes in 36 patients with peptic ulcer when they
      experienced exacerbation. Gastric and duodenal ulcer in exacerbation was
      accompanied by dysbacteriosis of the large intestine, uncontrolled augmentation
      of the processes of free-radical lipid oxidation against the background of
      impairment of functional systems of antiradical defence, which fact plays its
      part in relapsing of gastroduodenal ulcer.

PMID- 8983788
TI  - [Arterial hypertension and insulin resistance].
AB  - Insulin resistance manifested by hyperinsulinism is an important risk factor for
      the development of cardiovascular diseases. When associated with characteristic
      disorders of the lipid metabolism and arterial hypertension it is regarded today
      as a metabolic syndrome X. To detect hyperinsulinism in patients with arterial
      hypertension in everyday practice, it is advisable to determine the rations
      "circumference of the waist, circumference of the hips", while its abnormal
      values necessitate a carbohydrate challenge. Hyperinsulinism in AH patients
      should be born in mind when devising therapeutic measures, the mainstay of which
      is dietary therapy, with Calcium antagonists and inhibitors of the converting
      enzyme being used as hypotensive agents.

PMID- 8983791
TI  - [The clinico-pathogenetic validation of rehabilitative-stage treatment in chronic
      pancreatitis].
AB  - A total of 252 patients were examined. It has been shown that forms of chronic
      pancreatitis (ChP) have some distinguishing features of the clinical course of
      the disease and depend on morphofunctional state of pancreas, its ecbolic
      activity, degree of microcirculatory disorders, state of lipid peroxidation
      (LPO), that of the antioxidant system of defence as well as psychophysiologic
      status of the personality, circadian and seasonal variability of functional
      activity of pancreas in patients with chronic pancreatitis. Substantiated in the
      paper is rehabilitative staged treatment of ChP patients, depending on ChP forms
      with due regard to the above-mentioned mechanisms of its relapse, most important
      of which is LPO status, that of antioxidant system of defence and
      microcirculation.

PMID- 8983792
TI  - [The effect of selective proximal vagotomy on the content of prostaglandins and
      cyclic nucleotides of the blood and of the gastric mucosa].
AB  - Prostaglandins (PG) PGE2, PGF2, cAMP, cGMP were measured in blood plasma and
      gastric mucosa biopsy specimens from 42 patients with continuously relapsing
      peptic ulcer of duodenal localization, using radioimmunoassay. In duodenal ulcer,
      there occurs a significant increase in blood plasma levels of PGE2 and PGF2,
      while those of PGE2 in gastric mucosa biopsies are lowered. Selective proximal
      vagotomy is associated with a significant decrease in PGE2 and PGF2 in blood
      plasma and significant increase in PGE2 in a gastric mucosa biopsy. Cyclic
      nucleotides in blood plasma showed some tendency to rise. Preoperative level of
      cAMP in gastric mucosa biopsies tended towards increase which appeared to be
      statistically significant following the operation, cGMP was low both before and
      after the operation. The revealed changes in the levels of prostaglandins and
      cyclic nucleotides in patients with duodenal ulcer provide an additional index to
      be used while performing selective proximal vagotomy that results in their
      normalization.

PMID- 8983793
TI  - [Primary pulmonary tuberculosis in adults today].
AB  - An analysis was performed of statistical estimators of report forms of
      tuberculosis dispensary institutions, medical records of 557 patients with active
      pulmonary tuberculosis as well as autopsy materials that were those deceased (n =
      1864) who had died of tuberculosis of the respiratory organs over the period of
      45 years (1947-1991). Over the last few years, the frequency of primary forms of
      tuberculosis among adults was noted to be on the increase as was pathomorphosis
      of primary tuberculosis, which fact tends to change the clinical course of the
      illness and completion of a specific process.

PMID- 8983794
TI  - [The new pathogenetic agent lipin for the treatment of patients with respiratory
      failure].
AB  - Results are submitted of clinical trial of a new drug preparation lipin based on
      natural phospholipids. Overall fifty-three patients with various disorders of the
      respiratory system complicated by the respiratory distress syndrome received the
      drug. Lipin was found to have a positive effect on pulmonary ventilation and
      oxygen-transport functions, thereby lessening arterial hypoxemia. The drug
      preparation in question appeared to be of clinical benefit in as many as 94.3
      percent of the patients. It is concluded that lipin is worthy to come into
      widespread use in a variety of settings in medicine.

PMID- 8983795
TI  - [Pulmonary surfactant and dust-induced diseases of the respiratory organs in coal
      miners].
AB  - Surface activity and biochemical composition of pulmonary surfactant was studied
      in patients with anthracosilicosis and chronic dust-induced bronchitis.
      Significant impairment was found of surface-active properties of the surfactant
      during the course of development of the above conditions but different functional
      state of the pulmonary surfactant system determines dissimilarity in the natural
      course of the conditions in question. Suppression of the phospholipids synthesis
      in patients with anthracosilicosis contributes to the predominance of the
      processes of damaging the alveolar epithelium as well as pneumofibrosis and fatty
      infiltration of the pulmonary tissue while increase in the amount of pulmonary
      surfactant in patients with dust-induced bronchitis brings about predominant
      development of obstructive, bronchospastic and inflammatory changes. Study of the
      state of pulmonary surfactant in patients with dust-induced diseases of the
      respiratory organs suggest it is not useful to classify anthracosilicosis and
      dust-induced bronchitis under the same term "dust-induced disease of the lungs".

PMID- 8983797
TI  - [Laser fluorescence spectroscopy in cardiology: the problems and outlook].

PMID- 8983796
TI  - [The results of a clinical trial of flurenizid in phthisiopulmonology practice].
AB  - Flurenizide, a new home drug preparation, endowed with antituberculosis activity,
      was administered to 20 patients with freshly detected pulmonary tuberculosis, in
      combination with etambutole or rifampycin in a daily dose of 0.6 g. After the
      above chemotherapy, closure of the cavities, diminution in size and consolidation
      of the foci as well as infiltrates, dispelling of the symptoms of intoxication,
      and discontinuance of bacteria discharge were observable in 70.0 percent of the
      cases. The drug is well tolerated by patients and is not associated with side
      effects. The results obtained permit recommending flurenizide for use in
      phthisiopulmonological practice.

PMID- 8983798
TI  - [The level of free histamine and free serotonin in the blood plasma in
      polycythemia vera].
AB  - Fluorimetric analysis was performed of blood plasma content of free histamine and
      free serotonin in 26 patients with polycythemia vera (PV) and 29 essentially
      healthy individuals. There has been established an elevation of blood plasma free
      histamine and free serotonin concentration in PV patients (p) as compared with
      those in healthy subjects. The ratio of free histamine: free serotonin in PV
      patients' blood plasma has gotten significantly decreased (p) as compared with
      the healthy individuals. The above findings might be regarded as reflecting
      metabolic disorders due to retardation of bloodflow and increase in viscosity of
      blood caused by augmentation of the mass of circulating erythrocytes in PV.

PMID- 8983799
TI  - [The antioxidant effects of emoxipin in patients with iron-deficiency anemia].
AB  - A total of 78 female patients of child-bearing age with iron deficiency anemia
      (IDA) of varying genesis and degree of severity were examined for effectiveness
      of a synthetic antioxidant emoxypine in a combined treatment of IDA. IDA was
      found to be associated with activation of lipid peroxidation processes (LPO) and
      decrement in antioxidant defence of the body. Conventional antianemic therapy
      does not lead to normalization of parameters characterizing LPO. Incorporation
      into a complex therapy of a synthetic antioxidant emoxypine reduces activity of
      free-radical oxidation of lipids, which fact prevents the pathological process
      from progressing and leads to more rapid and lasting clinical remission.

PMID- 8983800
TI  - [The clinico-morphological characteristics and treatment of minimal-change
      glomerulonephritis and focal-segmental glomerulosclerosis-hyalinosis].
AB  - Clinical and morphological features were analysed of the morbid condition in 46
      patients with glomerulonephritis presenting with minimal alterations (GNMA) and
      12 those with focal-and-segmental glomerulosclerosis-hyalinosis (FSGH), of whom
      there were twenty nine males and twenty nine females ranging between 15 to 54
      years. In all cases morphologic diagnosis was established on the basis of vital
      histologic investigation of renal tissue. Immediate results were assessed of
      glucocorticoid and cytostatic therapy instituted at different stages of the
      condition. High effectiveness was documented of glucocorticosteroids in GNMA
      patients along with the ability of cyclophosphamide to significantly decrease the
      frequency of exacerbations and make such patients free from steroid dependency.
      GSGH patients derived no benefit from glucocorticoids while cyclophosphamide was
      associated with complete GH patients azathioprine therapy had no positive effect
      on the course of the illness.

PMID- 8983801
TI  - [The hemostatic system and thrombohemorrhagic complications during the
      hemosorption treatment of patients with chronic glomerulonephritis with nephrotic
      syndrome].
AB  - Effects were studied of hemosorption on the system of homeostasis in patients
      with chronic glomerulonephritis presenting with nephrotic syndrome. An optimum
      graphic express method of control of the homeostasis system state was found,
      permitting predicting thrombohemorrhagic complications after single-session
      hemosorption (significance 99.9%). Strategies were identified for correction of
      changes in coagulogrammes in such patients along with devising measures to
      prevent the above complications.

PMID- 8983803
TI  - [The prevalence of disseminated sclerosis in Ukraine].
AB  - Both geoclimatic factors and environmental contamination due to human activity in
      agriculture and industry have been implicated in the onset and course of
      disseminated sclerosis in Ukraine, according to epidemiological investigations.
      On the basis of the results obtained a conception has been advocated of the
      demyelinization process development as a consequence of the myelin protein
      metabolism control getting upset in the most differentiated system of those
      individuals genetically predisposed to the condition owing to aggravation of the
      endocrine disorders tending to occur in male subjects predominantly under the
      influence of geoclimatic factors while in females because of the environmental
      contamination. Peculiarities of formation in the evolutionary time scale of sex
      related adaptive defence mechanisms are thought to account for the above
      observation.

PMID- 8983802
TI  - [The clinico-immunological effects of T-activin in the combined treatment of
      patients with acute suppurative pyelonephritis].
AB  - Results were studied of use of T-activin in those clinical settings related to
      acute inflammatory diseases of the kidneys. There was a positive clinical effect
      from this preparation in all twenty-eight patients with acute purulent
      pyelonephritis, accompanied by readjustments in the patients' immune system. A
      rise to the norm was found to occur in T-helper counts, and accordingly,
      immunoregulatory index, NK-cell activity, blood microbocydic activity. The in
      vitro investigations done suggested the need for individual testing of
      immunocompetent cells of the patient to optimize the therapy.

PMID- 8983804
TI  - [The diagnosis of microcirculatory-rheological disorders and their correction in
      patients with the initial manifestations of insufficiency of the cerebral blood
      supply].
AB  - An evaluation was done of the state of bulbar microcirculation and aggregability
      of blood platelets in 47 patients presenting with early manifestations of
      cerebral circulatory insufficiency. A correlation was established between the
      revealed disturbances in the microcirculatory bed and augmentation of
      aggregational activity of thrombocytes. Computation of the integrative guide,
      microcirculatory-rheologic index, reflecting objectively the degree of
      intravascular hemocirculatory disorders has been performed. Treatment with
      calcium antagonist corinfar, antihypoxic agent actovegin was of particular
      benefit for the patients when administered in combination; more than half of the
      parameters characterizing microcirculation, rheologic properties of blood,
      microcirculatory-rheologic index have all returned to normal.

PMID- 8983805
TI  - [Secondary craniocerebral trauma in acute disorders of the cerebral circulation].
AB  - As many as 69 records were reviewed of those patients predominantly in older age
      bracket, in whom acute cerebral circulatory disorder (hemorrhage in 26,
      infarction of the brain in 8, transient cerebral circulatory disturbances in 35)
      was a cause of their falling and incurring a craniocerebral injury. The studies
      made suggest that prior history, somatoneurological examination, information
      provided by various investigational modalities, especially computerized
      tomographic imaging, all might serve to make the diagnosis of associated brain
      injury more precise.

PMID- 8983807
TI  - [The hormone level of the blood plasma in neurodermatitis patients and its
      dynamics during the performance of nondrug pathogenetic therapy].
AB  - Concentrations of hormones of the hypophysis, thyroid gland and adrenal cortex
      were measured in blood plasma of those patients presenting with neurodermatitis.
      A statistically significant reduction in the blood content of thyroid-stimulating
      hormone (TSH) and hydrocortisone and rise in aldosterone, adrenocorticotrophic
      hormone (ACTH), triiodothyronine and thyroxin were revealed in this patient
      population. Combined non-drug therapy treatments involving endovascular helium
      neon laser therapy and EHF electromagnetic radiation resulted in improvement in
      more than half of the measurements done: blood levels of TSH and hydrocortisone
      got increased while those of ACTH, thyroxin and aldosterone decreased, which fact
      correlated with the positive clinical picture of the condition in question.

PMID- 8983806
TI  - [Alkaline blood serum proteins in patients with the initial manifestations of
      cerebral arteriosclerosis and the late sequelae of mild closed craniocerebral
      trauma (comparative data)].
AB  - Alkaline proteins play their pathogenetic part in the course of cerebral
      atherosclerosis the development of which is accompanied by decline in their
      content. It has been ascertained that in patients with early cerebral
      atherosclerosis and remote sequelae of mild closed craniocerebral injury (RS
      MCCCI) the content of alkaline proteins is below the established norm. The
      absence of significant differences between the patients presenting with early
      manifestation of cerebral circulatory insufficiency and those with RS MCCCI may
      suggest similarity of mechanisms of development of vascular disorders of
      traumatic and atherosclerotic genesis.

PMID- 8983808
TI  - [The clinical efficacy of the Ukrainian preparation Ambocarb].

PMID- 8983809
TI  - [Changes in the intellectual productivity of patients with infantile cerebral
      palsy under the influence of a system of intensive neurophysiological
      rehabilitation].

PMID- 8983810
TI  - [The catabolism of polyamines].
AB  - The important role of the natural polyamines putrescine, spermidine and spermine
      in the normal and pathological cell growth is the main reason for the active
      investigation of their metabolism. The essential catabolic reactions of polyamine
      interconversion and terminal oxidation as well as data for the catabolic enzymes
      and the regulatory mechanisms of their activities are reviewed. The importance of
      catabolic reactions for the maintenance of the optimal polyamine concentrations
      during the cell growth and differentiation is also presented. The role of the
      essential catabolic enzymes spermidine/spermine N1-acetyltransferase, polyamine
      oxidase and diamine oxidase in normal and pathological cell growth is discussed.

PMID- 8983811
TI  - [The participation of nitric oxide in the functions of the central nervous system
      and the cardiovascular system].
AB  - Nitric oxide (NO) exerts its vasodilatator effect in smooth muscle by activation
      of guanylyl cyclase. This in turn leads to decreases in intracellular calcium and
      dephosphorylation of myosin light chains and relaxation. NO is synthesised from L
      arginine by a family of enzymes called Nitric oxide synthase (NOS). In the
      vascular system two isoenzymes of NOS are largely expressed: the constitutive NOS
      and the inducible NOS. The constitutive NOS identified in the endothelium
      generates NO continuously providing the vasodilatator tone and modulating
      platelet function. NOS type 1 is expressed in preoptic and infundibular nucleus
      of hypothalamus. NO acts as presynaptic agonist of glutamatergic NMDA-receptor
      mediation in the motor nucleus of nervus vagus. NO decreases the frequency of the
      spontaneous discharges in the carotid bodies. NO is involved in the processes of
      synaptic plasticity in the hippocampus.

PMID- 8983812
TI  - [The freeze-etching and freeze-fracturing technics and their use for studying
      cellular membranes in the central nervous system].
AB  - In the present review, both subkinds of the method for membrane splitting, namely
      freeze-etching and freeze-fracturing techniques, are presented. After a brief
      historical survey, a mechanism of their action is described. Special attention is
      paid to the consecutive stages in applying these techniques--fixation,
      fracturing, etching, replication, cleaning and observation. A new idea for a
      better cleaning of the replicas and an explanation of the different occurrence of
      intramembranous particles on the membrane fracture faces are proposed. Finally,
      the application of the freeze-etching and freeze-fracturing techniques to
      visualize the intramembranous structure of membranes in the central nervous
      system is outlined.

PMID- 8983813
TI  - [Molecular medicine--a challenge of the 21st century].

PMID- 8983814
TI  - [The insulin transduction system].
AB  - Insulin is a key hormone regulating glucose homeostasis and has many cellular
      effects on metabolism, growth, and differentiation. Insulin action is mediated
      through a specific cell-surface receptor. The first step following insulin
      binding consists in receptor autophosphorylation and stimulation of its tyrosine
      kinase activity. Among the multiple substrates, the insulin receptor substrate-1
      (IRS-1) is the major cytoplasmic substrate for insulin. IRS-1 binds several Src
      homology 2 (SH2) proteins through its multiple tyrosine phosphorylation sites:
      phosphatidylinositol 3-kinase (PI 3-kinase), the Ras guanine-nucleotide-releasing
      complex Grb2-SOS, the tyrosine phosphatase Syp, and the adapter protein Nck. IRS
      1 is essential for many, but not all of the insulin's biological responses.
      Recently, a primary alternative substrate, i.e. IRS-2, was purified and cloned.
      Numerous biochemical abnormalities of the insulin signaling system lead to
      insulin resistance. No doubt, the recent data about the molecular mechanisms of
      insulin action will provide new insights into the pathophysiology and therapy of
      diabetes and other insulin resistant states.

PMID- 8983815
TI  - [The T-cell receptor--its participation in the pathological immune response].
AB  - This work reviews clonal rearrangements of T-cell receptor genes in peripheral T
      cells of patients with lymphoproliferative diseases. The role of T-cell genes for
      predisposition to autoimmune diseases is analysed. Methodological approaches for
      analysis of T-cell receptor repertoire and autoimmune diseases are presented. The
      role of T-cell receptor-antigen recognitions in IgE mediated allergic reactions
      is described.

PMID- 8983816
TI  - [Utilization of thought stopping in the treatment of obsessive- compulsive
      disorder in a 9 year old girl].
AB  - OBJECTIVE: To use a pharmacobehavioural approach employing modified techniques of
      exposure, prevention of the response, and thought stopping in the treatment of
      obsessive-compulsive disorder in a 9-year-old girl. METHODS: The diagnosis of
      obsessive-compulsive disorder (OCD) was made based on the DSM-IV criteria. The
      patient was seen over 15 sessions, during which clomipramine was introduced and
      modified techniques of exposure, prevention of the response, and thought stopping
      were successively used. Follow-up extended over more than 18 months after the end
      of the therapy. RESULTS: The patient learned and used the behavioural techniques
      easily, and we observed a rapid, complete, and sustained disappearance of the
      obsessive-compulsive symptomatology. CONCLUSIONS: Use of a pharmacobehavioural
      approach in treating OCD in young children remains limited. Techniques used with
      adults and slightly modified to adapt them for children are, in our view, an
      avenue of treatment worth exploring.

PMID- 8983817
TI  - [Fraud and shoplifting].

PMID- 8983818
TI  - ["Double nodal pathway" as a common electrogenic pathway at the base of first and
      second degree paroxysmal atrioventricular node and nodal reentrant tachycardia].
AB  - The combined occurrence of conduction disturbances and reentry in subjects with a
      dual atrioventricular nodal pathway is extremely rare and poorly documented, only
      by means of short electrocardiographic strips. This case report deals with a
      young woman with frequent episodes of paroxysmal first- and second-degree type I
      atrioventricular block due to a dual atrioventricular nodal pathway at Holter
      monitoring, and atrioventricular nodal reentrant tachycardia inducible at
      transesophageal electrophysiologic study. This case confirms that some paroxysmal
      first- and second-degree atrioventricular block and the atrioventricular nodal
      reentrant tachycardia may share the same electrogenetic substrate represented by
      a dual atrioventricular nodal pathway. This finding may be of clinical
      significance because of its potential therapeutical implications. Further studies
      are needed in order to explain the rarity of this association.

PMID- 8983819
TI  - [Cardiomyoplasty].

PMID- 8983820
TI  - [Oxygen consumption during exercise in patients with heart failure].

PMID- 8983821
TI  - [Cardiac adaptation and maladaptation].

PMID- 8983822
TI  - [Guidelines in cardiology: how much and how are they transferable to the reality
      in health care?].

PMID- 8983823
TI  - [Septal hypertrophy in the hypertensive patient: clinical reality or curiosity].

PMID- 8983824
TI  - [Echography with contrast media. State of the art and future perspectives].

PMID- 8983825
TI  - [Incidence of peripheral vascular complications in subjects undergoing coronary
      angioplasty].
AB  - The peripheral vascular complications following cardiac catheterization for
      interventional procedures are increasing. The aim of our study is to evaluate the
      importance of the early removal of the arterial sheath in reducing vascular
      complications. We examined 451 consecutive patients, submitted to percutaneous
      transluminal coronary angioplasty (PTCA) by femoral approach. In 229 patients
      (Group A), we removed the arterial sheath 12-14 hours after PTCA; in 222 patients
      (Group B) the arterial sheath was removed as soon as possible at the end of PTCA.
      In 31 Group A and 5 Group B patients we performed a coronarographic study after
      12-14 hours. In total, 16 patients (11 Group A, 5 Group B) presented vascular
      complications. None of the risk factors that we have considered was predictive
      for complications, except that iliacofemoral atherosclerotic disease. In patients
      undergoing complex procedures we have found a greater amount of vascular
      complications. The coronarographic control revealed some pathologic lesion
      (dissection, occlusive thrombus) only in patients with clear ischemic signs or
      symptoms, both in Group A and B. In our opinion, an early removal of the arterial
      sheath reduces the incidence of vascular complications and the period of in
      hospital stay.

PMID- 8983826
TI  - [Ischemic cardiopathy in the young: coronarographic and autopsy picture in 100
      subjects].
AB  - Many aspects of coronary artery disease in young people are not completely
      understood. Our study concerns a series of 100 patients < 45 years with acute
      coronary artery disease. Sixty patients survived and 40 died suddenly. All
      subjects have been divided into four groups: Group I includes 20 deceased
      patients with anatomic features of acute myocardial infarction. Group II includes
      20 subjects dead without features of acute myocardial infarction. Group III
      includes 30 patients surviving the first acute myocardial infarction. Group IV
      includes 30 patients surviving unstable angina. The coronary arteries have been
      studied by anatomic dissection in Group I and II and with coronarography in
      Groups III and IV. The left main was only involved in Group I and II patients.
      Multivessel disease was more frequent in Group I and II, but the difference was
      not significant. These results underline that coronary artery disease with
      multivessel involvement is not rare in young patients. The rare occurrence of
      left main disease at coronary angiography could be the consequence of the natural
      preselection determined by sudden death.

PMID- 8983827
TI  - [Unstable angina in coronary intensive care units without hemodynamics: is
      admissible a strategy limiting the indications for coronarography?].
AB  - In coronary care units (CCU) without cardiac catheterization facilities, coronary
      angiography is rarely carried out when a successful medical treatment in the
      acute phase of unstable angina has been obtained. However, the unstable angina
      still has an uncertain prognosis when the remission of pain is obtained with
      drugs. This study presents a follow-up of 147 consecutive patients (aged 66.8 +/-
      10.4 years) admitted to our CCU in 1991 and 1992 for unstable angina; 33 of them
      (22.4%) were in Braunwald class I. 2 (1.4%) in class II and 112 (76.2%) in class
      III. The patients were treated according to the usual therapy protocols and class
      III patients received i.v. heparin. In selected cases we used thrombolysis (10
      patients) and intra-aortic balloon pump (5 patients). During hospitalization 1
      patient died (0.7%), 5 patients (3.4%) suffered an acute myocardial infarction
      and 9 patients (6.1%) had angina. Stabilization of unstable angina was achieved
      in 132 patients (89.9%): in 113 (76.8%) during the first 48 hours, and in 19
      (12.9%) later. Coronary angiography was carried out in non-stabilized patients
      and in 46 (34.8%) of the 132 with successful treatment (Group I). Eighty-six
      patients, without indication to coronary angiography were discharged in medical
      therapy (Group II). During the follow-up (mean of 15.0 +/- 9.0 months) Group I 10
      patients (18.2%) had cardiac events (death, myocardial infarction, or recurrent
      angina) vs 26 of Group II (p < 0.05). In Group I coronary angiography together
      with clinical criteria of high risk allowed the identification of candidates to
      coronary revascularization (61.8% of Group I patients while). These data show
      that the initial success of treatment during the acute phase of unstable angina
      should not be considered as a favourable prognostic index. Coronary angiography
      appears to be indicated for clinical evaluation and therapeutical decision.

PMID- 8983828
TI  - [Absence of an association of the D allele of the ACE gene with arterial pressure
      in mild-moderate essential arterial hypertension].
AB  - To assess the relationship between the angiotensin converting enzyme (ACE) gene
      I/D polymorphism, blood pressure (BP) and family history of hypertension, 133
      hypertensive subjects (mean age 50 +/- 9 years, 78 males, 55 females) were
      selected according to both casual supine BP > 140/90 mmHg and ambulatory BP >
      134/88 mmHg. Drug treatment was discontinued 2 weeks before entering the study.
      Subjects with myocardial ischemia, as well as those with "white coat"
      hypertension, were excluded. The study population was subclassified according to
      age < or = 50 years. Polymerase chain reaction was used to detect the I/D
      polymorphism of the ACE gene, and the DD genotype was analysed twice. The
      frequencies of the I and D allele were 42 and 58%, and the distribution of the
      ID+ II and DD genotypes were 69 and 31% respectively. No significant relation was
      found among ACE genotypes (DD vs ID+ II) and casual systolic or diastolic BP as
      well as ambulatory BP, both in the whole study population and in the
      subpopulation < 50 years old. No difference was found also in the distribution of
      dippers and no dippers, as well as in the distribution of subjects with a
      positive family history in the whole sample and hypertensives < 50 years old.

PMID- 8983829
TI  - [Transthoracic and transesophageal echocardiography].

PMID- 8983830
TI  - [Obesity and cardiorespiratory disease].

PMID- 8983831
TI  - [Sotalol, propafenone, and flecainide: compared multiparametric analysis of
      ventricular repolarization in subjects without organic cardiopathy].
AB  - Antiarrhythmic drugs are known to affect depolarization and repolarization time
      in a different fashion. The aim of the present study was to compare the effects
      of sotalol, flecainide and propafenone on some common (mean QT and QTc, mean JT
      and JTc), or uncommon (QTc dispersion, T-peak to T-end interval-Tp-Te)
      electrocardiographic parameters in order to evaluate the effects of these
      antiarrhythmic drugs on repolarization time. QTc dispersion, defined as the
      difference between maximum and minimum QTc calculated from the standard 12 ECG
      leads, and the average Tp-Te interval, reflect regional variation in ventricular
      repolarization. We have analyzed retrospectively the standard 12-lead
      electrocardiograms of 28 patients (15 females and 13 males, age 36.11 +/- 16
      years, range 11-67 years), recorded in the free-drug state and at the steady
      state after oral treatment with sotalol (160 mg/ die), flecainide (200 mg/die)
      and propafenone (450 mg/die). These drugs were prescribed, separately, for the
      treatment of patients with supraventricular tachycardia without underlying
      structural heart disease. Sotalol treatment prolongs ventricular repolarization
      times (QT, p = 0.0001; JT, p = 0.0001 and JTc, p = 0.0001) in an homogeneous
      fashion, as showed by the significant decrease in QTc dispersion (p = 0.026) and
      Tp-Te interval (p = 0.011). On the contrary, flecainide treatment is associated
      with an increase in QTc dispersion (p = 0.039) and Tp-Te interval (p = 0.0001),
      mean QT (p = 0.0001), QTc (p = 0.0001) and QRS (p = 0.0001), with no significant
      changes in JT and JTc (NS). Propafenone treatment does not affect repolarization
      time indexes, affecting only depolarization time as expressed by an increase in
      QRS (p = 0.046).

PMID- 8983832
TI  - [Describing and interpreting systemic hypertension in heart transplantation with
      non-invasive arterial pressure monitoring].
AB  - This investigation was performed in 34 heart transplanted patients (HTP), 28
      males and 6 females, mean age 49 +/- 13 years. The aim of the study was to detect
      hypertension in HTP by casual sphygmomanometry and non-invasive ambulatory blood
      pressure monitoring (ABPM). The evaluation of ABPM demonstrated that 71% out of
      the HTP was hypertensive because of some elevated blood pressure values scattered
      during the hours of the day and/or of the night. These hypertensives were found
      within the groups of normotensives as well as of hypertensives considered to be
      correctly treated. Fifty percent hypertensive HTP did not show the physiologic
      nocturnal decrease in blood pressure (non-dippers); 25% out of the non-dipper
      hypertensives showed absence of the blood pressure circadian rhythm,
      demonstrating that their hypertension was prevalently nocturnal and could not be
      detected by casual sphygmomanometry-The ABPM is recommended in clinical follow-up
      of HTP for a correct diagnosis of hypertension, which frequently complicates
      heart transplantation, and with the aim of avoiding hypertensive damage of the
      transplanted organ. The ABPM is useful for adjusting the antihypertensive
      therapy, in order to restore the blood pressure circadian rhythm.

PMID- 8983833
TI  - [Diagnostic imaging of aortic pseudoaneurysm: study of 4 clinical cases].
AB  - Aortic pseudoaneurysm starts as small disruption of the aortic wall with an
      extravasation of blood into the mediastinum, contained only by fibrous tissue and
      by parietal pericardium. The most common cause of this condition is dehiscence or
      inflammatory processes of suture stitches after surgical interventions on aortic
      value or ascending sorts. Pseudoaneurysm represents about 40% of complications of
      cardiac surgery involving the ascending sorts. This complication occurs in about
      1% of cases of aortic valve or ascending tract replacement. In this study, we
      evaluated, with different diagnostic techniques, 4 patients (all males, mean age
      48 +/- 23 years, range 17-74) affected by aortic pseudoaneurysm occurring at
      different times after surgical intervention on the sorts. Clinically only 1 of
      the 4 patients referred chest pain. Repeated chest radiography and cardiac
      magnetic resonance were performed in every patient; 3 subjects were evaluated by
      transthoracic and transesophageal echocardiography; contrast-enhanced computed
      tomography was performed in 1 patients. Pseudoaneurysm diagnosis obtained by non
      invasive methods was later confirmed and better described by angiography. Our
      study demonstrated that transesophageal echocardiography and magnetic resonance
      are useful and reliable methods in the diagnosis of aortic pseudoaneurysm.
      However, in case of mediastinal he or pericardial effusion (suggestive of aortic
      pseudoaneurysm) by transesophageal echocardiography or magnetic resonance,
      angiography is necessary and may show the exact rupture site on the aortic wall.
      This diagnostic approach yields enough information for both diagnosis and
      surgical correction of this rare but high-risk pathological condition.

PMID- 8983834
TI  - [Recurrent restenosis after angioplasty of anomalous right coronary artery].
AB  - An anomalous right coronary artery underwent successful percutaneous transluminal
      coronary angioplasty (PTCA) but exercise-induced myocardial ischemia persisted.
      Moreover, recurrent restenosis were angiographically documented and treated by
      repeat PTCA. Post-PTCA large atheroma burden not appreciable by angiography, high
      take-off, and tangential origin of the vessel from the aorta may be some of the
      mechanisms involved in myocardial ischemia persistence and restenosis of the
      vessel.

PMID- 8983835
TI  - [Riva-Rocci 100 years ago].

PMID- 8983836
TI  - [Percutaneous mitral valvuloplasty].

PMID- 8983837
TI  - [When the QRS becomes narrow].

PMID- 8983838
TI  - [Clinical medicine and technologic medicine at the threshold of the third
      millennium].

PMID- 8983839
TI  - [Myocardial echocontrastography in the study of myocardial infarct].

PMID- 8983840
TI  - [Endothelin-1 in ischemic cardiopathy].

PMID- 8983841
TI  - [Inotropic agents: why yes and why not].

PMID- 8983842
TI  - [At risk myocardium after acute infarct treated with fibrinolysis: assessment
      using exertion echocardiography and clinico-prognostic significance].
AB  - Several studies have been carried out on the role of exercise echocardiography
      for risk stratification after uncomplicated myocardial infarction. However, the
      diffusion of thrombolysis has entailed a remarkable change in the characteristics
      of these patients, with a major incidence of recurrent ischemic events or
      reinfarction in the follow-up. To test whether the predictive value of exercise
      echocardiography may be modified by thrombolytic treatment, we have studied 62
      patients with acute myocardial infarction undergoing lytic therapy (Group A),
      compared to 153 conventionally-treated patients (Group B). All patients were
      asymptomatic at the time of the test, performed by cycloergometer 14 days after
      hospital admission. In 125 patients (47 Group A and 78 Group B) predischarge
      coronary angiography was performed. The exercise test showed a lower, but not
      significant, rate of positive tests in Group A patients (51.6 vs 58.8%). However,
      a positive test was more frequent in the homozonal area among patients who
      underwent thrombolytic therapy (50% of positive tests vs 18% in Group B; p <
      0.001). Follow-up data (23 +/- 17 months) showed a higher but not significant
      rate of coronary events (cardiac death, reinfarction, severe angina, coronary
      bypass or angioplasty) in Group A patients with a positive test (62 vs 39% in
      Group B); however, in the subgroup with homozonal positive test, the event rate
      was much higher in Group A (77 vs 18% in Group B; p < 0.01). Furthermore, among
      patients with negative exercise test, coronary events were observed in 8% Group A
      and in 10% Group B patients. Therefore, our results show a higher percentage of
      homozonal exercise-induced ischemia with subsequent higher rate of coronary
      events in the thrombolyzed patients with respect to controls. This pattern is
      probably due to a higher rate of significant infarct-related residual stenosis,
      as coronary angiography have demonstrated. In conclusion, exercise
      echocardiography is useful in thrombolyzed patients, since it may better explore,
      rather than ECG, peri-necrotic areas.

PMID- 8983843
TI  - [Analysis of changes in repolarization for the differential diagnosis of narrow
      QRS supraventricular tachycardia and the site of the accessory pathway].
AB  - In view of the growing role of catheter ablation techniques for the treatment of
      supraventricular tachycardia, noninvasive determination of tachycardia mechanism
      and preliminary localization of the accessory pathway (AP) can simplify the
      cardiac catheterization procedure and reduce fluoroscopic exposure. The purpose
      of this study was to analyze the diagnostic value of repolarization changes
      during narrow QRS complex tachycardia (< 0.11 s). In 159 12-lead
      electrocardiograms during narrow QRS complex tachycardia (13 atrial tachycardias,
      57 atrioventricular (AV) node reentrant tachycardias and 89 AV reciprocating
      tachycardias), the following were evaluated: 1) the tachycardia cycle length; 2)
      the presence of QRS alternans > or = 1 mm in at least 6 leads; 3) the presence of
      ST segment depression > or = 2 mm and/or T wave changes (inversion, notching); 4)
      the duration of retrograde atrial activation during tachycardia (right atrium
      coronary sinus interval, in ms); the latter parameter, as well as tachycardia
      mechanism and accessory pathway location, were determined during an
      electrophysiologic study. There were no significant differences in mean cycle
      length among the groups. ST segment depression > or = 2 mm and/or T wave changes
      were present more often in AV reciprocating tachycardias (51/89) than in the
      other groups (AV node reentrant tachycardias: 14/57; atrial tachycardias: 1/13; p
      < 0.001), independently from the cycle length. Distinct patterns of
      repolarization changes during tachycardia were associated with different location
      of accessory pathway: ST segment depression from V3 to V6 in left lateral AP; T
      wave inversion in inferior leads in posterior-posteroseptal AP; T wave changes in
      V2 in all cases of anteroseptal AP location. The magnitude of ST segment
      depression, significantly more marked in the AV reciprocating tachycardias (1.3
      +/- 1.6 mm) than in AV node reentrant tachycardias (0.7 +/- 0.8 mm, p < 0.005),
      was directly related to the duration of atrial activation time during tachycardia
      (80 +/- 20 ms, and 32 +/- 12 ms, p < 0.001, respectively). The finding of ST
      segment depression and/or T wave changes during narrow QRS tachycardia suggest
      the presence of an AV reciprocating tachycardia; this phenomenon may be related
      to a different pattern of retrograde atrial activation. In conclusion, analysis
      of repolarization changes during narrow QRS tachycardia constitutes an additional
      electrocardiographic criterion to differentiate the tachycardia mechanism and,
      furthermore, can guide preliminary location of the AP, even in the absence of
      ventricular preexcitation.

PMID- 8983844
TI  - [Aging and isomyosin pattern of the left ventricle in spontaneously hypertensive
      and Wistar Kyoto rats].
AB  - Changes of the contractile proteins in the left ventricle from spontaneously
      hypertensive rats (SHR) are extensively documented with the development of the
      hypertensive state and with ageing. This study was undertaken to determine
      whether also the left ventricle from normotensive rats exhibits age-related
      changes of the myosin pattern. The relative distribution of myosin isoforms was
      investigated in Wistar Kyoto (WKY, n = 50) and SHR (n = 50), both at the 5th,
      9th, 24th, 48th and the 72nd week of life. A significant decrease in V1 as well
      as an increase in V3 percentage values, compared to the data obtained at the 5th
      week were observed in SHR from the 9th week, concomitantly to the rise in blood
      pressure values. These changes were more consistent with ageing (5 weeks: V1 99.0
      +/- 0.9%, V2 0.6 +/- 0.1%, V3 0.4 +/- 0.3%; 72 weeks: V1 5.3 +/- 3.9%, V2 3.0 +/-
      2.7%, V3 91.7 +/- 9.7%). In WKY rats, a significant decrease in V1 percentage
      values was detected at the 24th week and it was evident till the 72nd week. V3
      significantly changed only at the 48th and the 72nd week (5 weeks: V1 100.0 +/-
      0.0%; 72 weeks: V1: 41.4 +/- 6.5%, V2 13.3 +/- 2.8%, V3 45.5 +/- 6.9%). The
      results of this study confirm that alterations in the left ventricle isomyosin
      pattern occur early in SHR with the rise in blood pressure values and the
      increase in left ventricular mass. In contrast, modifications in the myosin
      isoform distribution were found only in WKY with ageing. These findings may be
      related to the biochemical changes occurring in the myocardial tissue either
      gradually, during the advanced ages of life, or early due to the hypertensive
      state.

PMID- 8983845
TI  - [Thiamine-deficiency cardiopathy: a rare cause of cardiac failure in childhood].
AB  - Cardiac beriberi is a rare cause of heart failure in infancy and the diagnosis is
      often very difficult. We describe the case of a 4-year-old girl admitted to our
      Hospital with symptoms of heart failure and diagnosis of myocarditis. In children
      with acute cardiac failure and suggestive history and signs of peripheral
      neuropathy, thiamine deficiency should be suspected.

PMID- 8983846
TI  - [A new frontier: cardio-oncology].

PMID- 8983847
TI  - [Mechanical prevention of pulmonary thromboembolism].

PMID- 8983848
TI  - Pharmacological and functional properties of voltage-independent Ca2+ channels.
AB  - During the last few years, considerable progress has taken place in our knowledge
      of the molecular and functional properties of the various voltage-independent
      Ca2+ channels. In addition to the ionotropic receptor-channels (ROCs), that are
      not discussed in the present review, these channels include the SMOCs, activated
      via second messengers or other transducing processes directly triggered by
      receptor activation; and the SOCCs, activated as a consequence of depletion of
      the rapidly exchanging Ca2+ stores in the cytoplasm. In parallel, a
      pharmacological approach to the study of these channels has been developed, based
      primarily on heterogeneous drugs already known for different biological effects,
      and subsequently recognized as voltage-independent Ca(2+)-channel blockers. From
      the systematic analysis of the effects of these drugs new information has emerged
      about SMOCs and SOCCs function. In addition, pharmacological blockade of these
      channels appears to have beneficial therapeutic effects in pathological
      conditions such as tumoral cell growth, inflammation and immunity. At the moment
      the field is rapidly evolving, with major developments expected in the years
      ahead.

PMID- 8983849
TI  - Laser scanning microscopy and calcium imaging.

PMID- 8983850
TI  - Distinct Ca2+ response patterns in human natural killer cells during induction of
      necrosis or apoptosis of target cells.
AB  - Human CD3-, CD16+ natural killer cells (NKs) induced necrosis in the cell line
      K562 and the minor population of MOLT-4, while induced apoptosis in the majority
      of MOLT-4, in one-to-one cell interaction. Simultaneous Ca2+ imaging of NK and
      target cells revealed remarkable differences in changes of cytosolic Ca2+
      concentration ([Ca2+]i) during the process of distinct target cell killing. A
      rapid [Ca2+]i rise in NK was generated within 2 min after contact with any
      target. For induction of necrosis, the [Ca2+]i rise in NK reached a peak of 580
      +/- 195 nM (mean +/- SD, n = 41) and was followed by an abrupt large [Ca2+]i rise
      in target cells probably due to Ca2+ entry through pores formed by perforin which
      was released from NK. The interval between onsets of NK and target Ca2+ responses
      (Tnk-t) was shorter than 3 min in most cases. Target cells were soon
      permeabilized, and NK Ca2+ responses ceased in 14 +/- 7 min. For induction of
      apoptosis, NK Ca2+ responses were relatively smaller (405 +/- 125 nM, n = 16),
      and Tnk-t was widely scattered up to 30 min. NK Ca2+ responses lasted much longer
      in a form of Ca2+ oscillations (total duration, 66 +/- 33 min) in parallel with
      target Ca2+ responses, and ceased as apoptotic changes such as cellular and
      nuclear fragmentation advanced. The difference in Tnk-t suggests that rapid
      synchronous release of perforin tends to cause necrosis rather than apoptosis.
      The duration of NK Ca2+ responses suggests that some 'off signals' may be
      transmitted to NK following recognition of target cell damage.

PMID- 8983851
TI  - Fluorescent analysis in polarized MDCK cell monolayers: intracellular pH and
      calcium interactions after apical and basolateral stimulation with arginine
      vasopressin.
AB  - Intracellular calcium ([Ca2+]i) and hydrogen ion concentrations (pHi) are
      important regulators of cell function. Those ions also may interact and it is
      important, therefore, to measure their concentrations simultaneously. In the
      present studies we used a system developed for that purpose, a fluorescent
      emission ratio technique for simultaneous analysis of calcium (Indo-1) and pH
      (SNARF-1) in single cells at video rates, and determined if arginine vasopressin
      (AVP, 12.5 mumol/l) evoked [Ca2+]i and pHi signals interact in MDCK cells. We
      also employed a simple system for analysing the side specific (basolateral or
      apical) application of agonist to polarized cell layers on permeable membranes.
      AVP is found to evoke simultaneous changes in both pHi and [Ca2+]i. Basolateral
      application induced transient acidification, followed by partial recovery, and a
      [Ca2+]i transient with kinetic pattern similar to that of the pHi. Apical
      application also caused a mirror image pHi and [Ca2+]i pattern but of smaller
      magnitude (no peak). Selective removal of extracellular calcium ([Ca2+]e) or
      sodium ([Na+]e) dissociated the pHi and [Ca2+]i responses in both cases. Na+e
      removal abolished the pHi changes, but not the [Ca2+]i transients. [Ca2+]e
      removal abolished the [Ca2+]i changes and reduced, but did not abolish, the pHi
      responses. Thus, AVP induces pHi changes which are modified by calcium while
      calcium signalling is not modified by changes in pHi.

PMID- 8983853
TI  - Spontaneous transients of [Ca2+]i depend on external calcium and the activation
      of L-type voltage-gated calcium channels in a clonal pituitary cell line (AtT-20)
      of cultured mouse corticotropes.
AB  - Spontaneous transients of [Ca2+]i were recorded from single nonstimulated cells
      of a clonal pituitary cell line of corticotropes, AtT-20/D16v. The spontaneous
      [Ca2+]i transients were dependent on calcium entry from the extracellular
      solution because they were abolished both in the absence of extracellular calcium
      and with the addition of cobalt to the calcium-containing extracellular solution.
      Calcium entry occurred through voltage-gated (VGCC) L-type calcium channels
      because the [Ca2+]i transients were blocked by L-type calcium channel
      antagonists, e.g. nifedipine, and were unaffected by the addition of
      tetrodotoxin. Bay K 8644 (1 microM) induced transient increases in [Ca2+]i which
      were also blocked reversibly by either the absence of extracellular calcium or
      the addition of an L-type calcium channel antagonist (e.g. nifedipine). The
      resting levels of [Ca2+]i and the frequency, but not the amplitude or duration,
      of the spontaneous [Ca2+]i transients increased as the concentration of
      extracellular calcium was elevated in concentrations ranging from 1.8-7.2 mM.
      Potassium depolarization reversibly elevated resting levels of [Ca2+]i and
      initiated the spontaneous calcium transients. These results indicate that
      extracellular calcium modulates the frequency of spontaneous [Ca2+]i transients
      in AtT-20 cells which are caused by the activation of L-type calcium channels by
      a spontaneous increase in the permeability of the cell membrane to calcium.

PMID- 8983852
TI  - Interactions between inositol trisphosphate and Ca2+ dependent Ca2+ release
      mechanisms on the endoplasmic reticulum of permeabilised bovine aortic
      endothelial cells.
AB  - In this paper we describe data from cultured bovine aortic endothelial (BAE)
      cells demonstrating a Ca2+ induced Ca2+ release (CICR) process which appears to
      have pharmacological properties different from CICR mechanisms in other cell
      types. CICR was measured in saponin permeabilised cells in which the internal
      stores had been preloaded with 45Ca2+. Step increases in the free Ca2+
      concentration of the bathing solution, from 10 nM up to 10 microM were found to
      increase 45Ca2+ loss. This process was completely inhibited by ruthenium red.
      Caffeine induced a small release of 45Ca2+ and the response to a subsequent
      stimulation with a Ca2+ step was reduced. In intact cells, ryanodine activated
      small oscillations in intracellular Ca2+ in the presence, but not the absence, of
      external Ca2+. However, in permeabilised cells, ryanodine had no effect on either
      basal efflux or the increased efflux of 45Ca2+ seen following a step increase in
      free Ca2+. These data suggest the operation of a ruthenium red sensitive but
      ryanodine insensitive CICR mechanism on the endoplasmic reticulum (ER) which may
      also be modulated by caffeine. An IP3 dependent 45Ca2+ release was also observed.
      In the presence of ruthenium red, the IP3 induced 45Ca2+ release was reduced
      suggesting that CICR may operate to amplify the magnitude of the IP3 response.
      The Ca2+ dependence of the IP3 induced release was also measured. Co-operativity
      between IP3 and Ca2+ could not be detected between 100-300 nM Ca2+. The results
      suggest that the regulation of IP3 induced Ca2+ release may be different in BAE
      cells, and point to the operation of a 'novel' CICR process and to complex
      interactions between Ca2+ release systems in BAE cells.

PMID- 8983854
TI  - Selection of fluorescent ion indicators for simultaneous measurements of pH and
      Ca2+.
AB  - The advent of fluorescent ion sensitive indicators has improved our understanding
      of the mechanisms involved in regulating pHi and [Ca2+]i homeostasis in living
      cells. However, changes in [Ca2+]i can alter pHi regulatory mechanisms and vice
      versa, making assignment of either ion to a particular physiological response
      complex. A further complication is that all fluorescent Ca2+ indicators are
      sensitive to protons. Therefore, techniques to simultaneously measure these two
      ions have been developed. Although several combinations of pH and Ca2+ probes
      have been used, few systematic studies have been performed to assess the validity
      of such measurements. In vitro analysis (i.e. free acid forms of dyes) indicated
      that significant quenching effects occurred when using specific dye combinations.
      Fura-2/SNARF-1 and MagFura-2/SNARF-1 probe combinations were found to provide the
      most accurate pH and [Ca2+] measurements relative to Fluo-3/SNARF-1, Ca2+-Green
      1/SNARF-1, or BCECF/SNARF-1. Similar conclusions were reached when probes were
      calibrated after loading into cells. The magnitude of interactions between pH and
      Ca2+ probes could be a factor which may limit the use of certain specific
      combinations. Loading of probes that exhibit interactions into distinct
      intracellular compartments (i.e. separated by a biological membrane) abolished
      the quenching effects. These data indicate that interactions between the probes
      used to simultaneously monitor pH and Ca2+ must be considered whenever probe
      combinations are used.

PMID- 8983855
TI  - cGMP is not required for capacitative Ca2+ entry in Jurkat T-lymphocytes.
AB  - In this study, we have addressed the potential role of cGMP in regulating calcium
      entry in Jurkat T-lymphocytes. These cells display capacitative Ca(2+)-entry in
      response to the intracellular Ca(2+)-ATPase inhibitor, thapsigargin (TG). In the
      presence of extracellular Ca2+, TG stimulates a sustained elevation of
      intracellular cGMP levels. In the absence of extracellular Ca2+, TG induces no
      apparent increase in the levels of cGMP. However, experiments using Mn2+, as a
      surrogate for Ca2+, demonstrated that TG increased the rate of divalent cation
      entry in the absence of extracellular Ca2+. Treatment of Jurkat cells with the
      guanylyl cyclase inhibitor, LY83583 (20 microM), completely blocked cGMP
      formation in response to TG. However, LY83583 treated cells still exhibited a
      sustained, albeit partially reduced, Ca2+ response induced by TG. These data
      demonstrate that, in Jurkat cells, the sustained formation of cGMP is dependent
      on elevated intracellular Ca2+, and that elevated levels of cGMP are not
      necessary for the activation of capacitative Ca2+ entry.

PMID- 8983856
TI  - Near membrane Ca2+ changes resulting from store release in neutrophils: detection
      by FFP-18.
AB  - FFP-18 was incorporated into the inner face of the plasma membrane of human
      neutrophils by incubation with its acetoxymethyl ester. Conversion to the Ca2+
      sensitive intracellular indicator was monitored by the change in excitation
      spectra. The fluorescence from extracellularly facing FFP-18 was quenched by the
      membrane impermeant ion Ni2+. Ratio fluorescence measurement of FFP-18 under
      these conditions permitted the detection of near membrane Ca2+ changes resulting
      from the release of Ca2+ from intracellular stores. Near membrane and cytosolic
      Ca2+ changes were measured under conditions in which store release and Ca2+
      influx were triggered by FMLP, thapsigargin or immune complexes. There were
      significant differences in the timing and magnitude of Ca2+ changes near the
      plasma membrane and bulk cytosolic Ca2+ concentration, which were consistent with
      a Ca2+ storage site deep within the neutrophil released by thapsigargin and FMLP,
      but Ca2+ release sites with immune complex stimulation being close to the
      membrane. The use of FFP-18 to monitor Ca2+ near the inner face of the plasma
      membrane thus provides evidence for the existence of two distinct Ca2+ storage
      locations in neutrophils.

PMID- 8983857
TI  - New volatile anaesthetics in cardiovascular anaesthesia: one step forward, two
      steps back?

PMID- 8983858
TI  - Clinical pharmacokinetics of zidovudine. An update.
AB  - The battle against the acquired immune deficiency syndrome (AIDS) is now into its
      second decade, and substantial advancements have been made in our understanding
      of the complex life cycle of, and the immunopathology associated with, human
      immunodeficiency virus (HIV) infection, as well as of the drugs used to modify
      the course of disease. Zidovudine was the first agent approved for treatment of
      HIV disease, and since its widespread availability in 1987 the pharmacokinetic
      disposition and clinical effects of zidovudine have been extensively evaluated.
      This article reviews the absorption, distribution, metabolism and elimination
      characteristics of zidovudine, focusing on more recent information. In addition,
      factors that may or may not affect zidovudine disposition are discussed. These
      include selected drug interactions and concomitant disease states such as renal
      and hepatic insufficiency. Issues such as bodyweight normalisation, maternal
      fetal transfer, pregnancy and intracellular phosphorylation are discussed in
      relation to the pharmacokinetics and clinical efficacy of zidovudine. Finally,
      information regarding the clinical pharmacodynamics of zidovudine is presented.
      This includes possible relationships between zidovudine pharmacokinetics and
      markers of efficacy and toxicity, and the significance of linking pharmacokinetic
      and pharmacodynamic information.

PMID- 8983860
TI  - Warfarin withdrawal. Pharmacokinetic-pharmacodynamic considerations.
AB  - Warfarin, like all the 4-hydroxycoumarin compounds, has an asymmetric carbon
      atom. The clinically available warfarin preparations consist of a racemic mixture
      of equal amounts of 2 distinct S and R isomers, the former being 4-times more
      potent as anticoagulant and more susceptible to drug interaction. Warfarin is
      highly water soluble and rapidly absorbed from the stomach and the upper
      gastrointestinal tract; its plasma concentrations peak 60 to 90 minutes after
      oral administration. Warfarin binds to the enzyme vitamin K 2,3-epoxide reductase
      in liver microsomes, stopping the cycle of vitamin K and reducing gamma
      carboxylation of the precursors of vitamin D-dependent pro- and anticoagulant
      factors. A variable fraction of the binding with the target enzyme, albeit small,
      can be reversed by competitive displacers, such as dithiol-reducing agent
      activity. Differences in dithiol-reducing activity have been suggested as a
      contributing factor to the wide interindividual differences in sensitivity to
      oral anticoagulants. The anticoagulant effect is caused by a small fraction of
      the drug, since most (97 to 99%) is protein bound (mainly to albumin) and
      ineffective. Drugs that can displace the albumin binding will increase the action
      of warfarin, even though this effect is counteracted by a more rapid elimination
      of the drug. The elimination half-life of warfarin varies greatly among
      individuals, ranging from 35 to 45 hours; the S isomer has, however, an average
      half-life shorter than the R isomer. The plasma levels of vitamin K-dependent
      proteins are determined by a dynamic equilibrium between their synthesis and half
      life times. The delay before warfarin takes effect reflects the half-life of the
      clotting proteins; the levels of factor VII and protein C (with shorter half
      lives) are reduced earlier, reaching steady inhibited levels in about 1 day,
      whereas factor II takes more than 10 days. Oral anticoagulant therapy (OAT) with
      warfarin or other coumarin derivatives is increasingly administered to patients
      for primary or secondary prevention of various arterial or venous thromboembolic
      diseases. If in some clinical conditions OAT is given indefinitely, in others-
      such as venous thromboembolism or after tissue heart valve replacement-
      anticoagulants are usually given only for the high risk period of thrombotic
      complication. A recent large prospective study performed by the Italian
      Federation of Anticoagulation Clinics showed that about 30% of the patients who
      began OAT for various clinical indications stopped treatment at different times,
      confirming that withdrawal from OAT is an occurrence that affects a large number
      of patients. The expression 'rebound phenomenon' was adopted to indicate a
      hypercoagulant condition occurring after warfarin withdrawal. A possible more
      frequent recurrence of thromboembolism after cessation of anticoagulation became
      a matter of controversy and many clinical studies, mostly observational and
      noncontrolled, reported on the issue with inconsistent results. Most
      authoritative commentators agreed that rebound phenomenon, though possible, was
      not clinically relevant and did not differ in frequency and intensity according
      to mode of withdrawal. Scientific interest in the topic waned until more
      sensitive methods for investigating blood hypercoagulability became available. In
      recent years, many studies (reviewed in the text) have investigated the levels of
      different markers of hypercoagulability [fibrinopeptide A, activated factor VII,
      prothrombin fragments F1+2, thrombin-antithrombin complexes, D-dimers (DD)],
      consistently finding an increase in their values after cessation of
      anticoagulation. Changes in the levels of markers of activated blood coagulation
      were prospectively investigated by our group in 32 patients with venous
      thromboembolism who were randomly withdrawn abruptly or gradually from warfarin
      treatment. Our results indicate that interruption of anticoagulant treatment
      frequently elicits low grade acti

PMID- 8983862
TI  - Role of nitric oxide in immune-mediated diseases.

PMID- 8983863
TI  - Sex differences in correlates of steady state and pulsatile component of blood
      pressure.
AB  - 1. The aim of the present study was to evaluate whether metabolic factors are
      linked to the steady component and the pulsatile component of blood pressure,
      evaluated as mean arterial pressure and pulse pressure respectively, in a sex
      specific manner. 2. A cohort of 299 subjects (152 males, 147 females; 25-80 years
      of age) was studied. Patients presenting congestive heart failure, coronary
      insufficiency, severe valvular heart disease, neurological accident in the last 6
      months, renal or respiratory failure, cancer, diabetes mellitus or acute
      infectious disease were excluded. None of the women was taking oral
      contraceptives or oestrogen supplementation. All cardioactive drugs were
      withdrawn at least 2 weeks before the subjects entered the study. 3. Men
      presented higher mean arterial pressure (120 +/- 15 compared with 115 +/- 16
      mmHg, P < 0.01) and lower pulse pressure values (63 +/- 16 compared with 67 +/-
      18 mmHg, P < 0.05) than women. In men, no significant relation between mean
      arterial pressure and the tested variables was detected; multiple regression
      analysis demonstrated that age contributed independently to the model for pulse
      pressure with a multiple r2 of 0.10 (P < 0.01). In women, body mass index
      contributed independently to the model for mean arterial pressure, with a
      multiple of 0.12 (P < 0.005); age and, to a lesser extent, body mass index,
      glycaemia and triglyceridaemia persisted as independent determinants of pulse
      pressure at the multiple regression analysis, with a multiple r2 of 0.20 (P <
      0.001). 4. Our findings suggest that metabolic risk factors are associated
      differently with pulse pressure and mean arterial pressure values in the two
      sexes.

PMID- 8983861
TI  - Pharmacokinetic individualisation of zidovudine therapy. Current state of
      pharmacokinetic-pharmacodynamic relationships.
AB  - Zidovudine is the cornerstone of current antiretroviral treatment of human
      immunodeficiency virus (HIV) infection. Its use, however, frequently leads to
      adverse reactions, including myelosuppression. Zidovudine pharmacokinetics show
      large interindividual variation with indications of pharmacokinetic
      pharmacodynamic relationships, but a clear therapeutic window has not yet been
      defined. Individualisation of zidovudine therapy with monitoring of drug
      concentrations might be desirable. This review considers (intracellular)
      monitoring of zidovudine and anabolites for individualisation of zidovudine
      therapy and the achievements in describing pharmacokinetic-pharmacodynamic
      relationships so far.

PMID- 8983864
TI  - Reproducibility of heart rate variability measures in patients with chronic heart
      failure.
AB  - 1. In patients with chronic heart failure, heart rate variability is reduced with
      relative preservation of very-low-frequency power (< 0.04 Hz). Heart rate
      variability has been measured without acceptable information on its stability and
      the optimal recording periods for enhancing this reproducibility. 2. To this aim
      and to establish the optimal length of recording for the evaluation of the very
      low-frequency power, we analysed 40, 20, 10 and 5 min ECG recordings obtained on
      two separate occasions in 16 patients with chronic heart failure. The
      repeatability coefficient and the variation coefficient were calculated for the
      heart rate variability parameters, in the time-domain (mean RR, SDRR and pNN50),
      and in the frequency-domain: very low frequency (< 0.04 Hz), low frequency (0.04
      0.15 Hz), high frequency (0.15-0.40 Hz), total power (0-0.5 Hz). 3. Mean RR
      remained virtually identical over time (variation coefficient 8%). The
      reproducibility of time-domain (variation coefficient 25-139%) and of spectral
      measures (variation coefficient 45-111%) was very low. The stability of the heart
      rate variability parameters was only apparently improved after square root and
      after log transformation. 4. Very-low-frequency values derived from 5 and 10 min
      intervals were significantly lower than those calculated from 40 and 20 min
      intervals (P < 0.005). Discrete very-low-frequency peaks were detected in 11 out
      of 16 patients on the first 40, 20 and 10 min recording, but only in seven out of
      16 when 5 min segments were analysed. 5. The reproducibility of both time or
      frequency-domain measures of heart rate variability in patients with chronic
      heart failure may vary significantly. Square root or log-transformed parameters
      may be considered rather than absolute units in studies assessing the influence
      of management on heart rate variability profile. Recordings of at least 20 min in
      stable, controlled conditions are to be recommended to optimize signal
      acquisition in patients with chronic heart failure, if very-low-frequency power
      in particular is to be studied.

PMID- 8983865
TI  - Lipid-lowering for prevention of coronary heart disease: what policy now?
AB  - 1. Recent outcome trials suggest that lipid-lowering with 3-hydroxy-3
      methylglutaryl-coenzyme A reductase inhibitors is justifiable on risk-benefit
      grounds in subjects with serum cholesterol > 5.5 mmol/l who have coronary heart
      disease, other forms of atherosclerotic vascular disease, or who are free of
      vascular disease but have a risk of major coronary events > or = 1.5% per year.
      Choice of an appropriate treatment policy will require (i) knowledge of the
      proportion of the population who will need treatment for secondary prevention,
      and (ii) targeting of treatment for primary prevention at a specified absolute
      risk of coronary heart disease events. Selection of an appropriate coronary heart
      disease risk for primary prevention requires consideration of the number needed
      to be treated to prevent one coronary heart disease event, the proportion of the
      population requiring treatment, the cost-effectiveness of treatment and the total
      cost of treatment. 2. In a random stratified sample of subjects aged 35-69 years
      from the Health Survey for England 1993 we first examined the prevalence of
      subjects with cardiovascular disease and serum cholesterol > 5.5 mmol/l who may
      be candidates for secondary prevention. In those free of cardiovascular disease
      we then examined the prevalence of subjects with serum cholesterol > 5.5 mmol/l
      who had three different levels of coronary heart disease risk: coronary heart
      disease event rates of 4.5% per year, 3.0% per year and 1.5% per year. These
      subjects may be candidates for primary prevention depending on the treatment
      policy selected. 3. For secondary prevention, 4.8% (95% confidence interval 4.3
      5.3) of the U.K. population aged 35-69 years might be candidates for 3-hydroxy-3
      methylglutaryl-coenzyme A reductase inhibitor treatment, comprising 2.4% (2.0 to
      2.7) with a history of myocardial infarction, 1.9% (1.6 to 2.2) with angina and
      0.5% (0.3-0.7) with a history of stroke--all with total cholesterol > 5.5 mmol/l.
      The prevalence of these diagnoses with total cholesterol > 5.5 mmol/l increased
      with age, from 1.5% at age 35-39 years to 16.2% at age 65-69 years in men, and
      from 0.2% at age 35-39 years to 10.0% at age 65-69 years in women. Approximately
      13 people would need treatment for 5 years to prevent one coronary event, at a
      cost of 36,000 pounds per event prevented. The number needing treatment for
      secondary prevention would increase substantially if treatment was extended to
      patients above 70 years of age or to those with serum cholesterol < or = 5.5
      mmol/l. 4. Primary prevention aimed at a coronary event risk of 4.5% per year
      would lead to treatment of only 0.3% (0.2-0.4) of those aged 35-69 years, and
      those treated would be predominantly older men with additional risk factors for
      coronary heart disease. The number needed to be treated and cost per coronary
      event prevented would be similar to those for secondary prevention. 5. Primary
      prevention targeted at subjects with a coronary event rate of 3.0% per year would
      entail treating 3.4% (3.0-3.9) of all those aged 35-69 years. At this level of
      risk, 20 people would need treatment for 5 years to prevent one coronary event,
      at a cost of 55,000 pounds per event prevented. 6. Primary prevention aimed at a
      coronary event rate of 1.5% per year would entail treating 19.6% (18.7-20.6) of
      all subjects aged 35-69 years, and about 80% of men aged 60-69 years for primary
      or secondary prevention. At this level of risk, 40 people would need treatment
      for 5 years to prevent one event, at a cost of 111,000 pounds per event saved. 7.
      Guidelines for 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor
      treatment should take into account the considerable workload and financial
      resources needed to implement secondary prevention of coronary heart disease, the
      accepted first priority. For primary prevention they need to consider the number
      needed to be treated to prevent one event, the number of subjects needing
      treatment, the cost-effectiveness of treatment and

PMID- 8983859
TI  - Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical implications.
AB  - Malaria is associated with a reduction in the systemic clearance and apparent
      volume of distribution of the cinchona alkaloids; this reduction is proportional
      to the disease severity. There is increased plasma protein binding, predominantly
      to alpha 1-acid glycoprotein, and elimination half-lives (in healthy adults
      quinine t1/2z = 11 hours, quinidine t1/2z = 8 hours) are prolonged by 50%.
      Systemic clearance is predominantly by hepatic biotransformation to more polar
      metabolites (quinine 80%, quinidine 65%) and the remaining drug is eliminated
      unchanged by the kidney. Quinine is well absorbed by mouth or following
      intramuscular injection even in severe cases of malaria (estimated
      bioavailability more than 85%). Quinine and chloroquine may cause potentially
      lethal hypotension if given by intravenous injection. Chloroquine is extensively
      distributed with an enormous total apparent volume of distribution (Vd) more than
      100 L/kg, and a terminal elimination half-life of 1 to 2 months. As a
      consequence, distribution rather than elimination processes determine the blood
      concentration profile of chloroquine in patients with acute malaria. Parenteral
      chloroquine should be given either by continuous intravenous infusion, or by
      frequent intramuscular or subcutaneous injections of relatively small doses. Oral
      bioavailability exceeds 75%. Amodiaquine is a pro-drug for the active
      antimalarial metabolite desethylamodiaquine. Its pharmacokinetic properties are
      similar to these of chloroquine although the Vd is smaller (17 to 34 L/kg) and
      the terminal elimination half-life is 1 to 3 weeks.

PMID- 8983866
TI  - Effect of a physiological insulin infusion on the cardiovascular responses to a
      high fat meal: evidence supporting a role for insulin in modulating postprandial
      cardiovascular homoeostasis in man.
AB  - 1. While the haemodynamic adjustments occurring after meal ingestion and the
      different effects of meals of different composition on these changes are well
      established, the mechanisms underlying these changes are less clear. Insulin,
      which has been shown to be both a positive inotrope and to stimulate
      vasodilatation in the skeletal muscle vascular bed, may account for the different
      cardiac and regional haemodynamic responses to high fat and high carbohydrate
      meals. 2. This study assessed the effect of an insulin infusion reproducing the
      plasma insulin profile seen after a high carbohydrate meal on the cardiovascular
      and regional haemodynamic response to a high fat meal. All measurements were
      carried out non-invasively in nine healthy lean subjects (mean age 24.5 +/- 1.3
      years). 3. The high fat meal resulted in increases in cardiac output (0.7 +/-
      0.32 l/min, P < 0.001), heart rate (7.8 +/- 2.1 beats/min, P < 0.001) and insulin
      (25.1 +/- 4.2 m-units/l, P < 0.001), and a decline in systemic vascular
      resistance (-1.9 +/- 0.9 units, P < 0.05) and superior mesenteric artery vascular
      resistance (-45 +/- 9 units, P < 0.01). After the high fat meal alone, calf
      vascular resistance and blood pressure did not change. After the high fat meal
      accompanied by insulin (peak insulin 86.1 +/- 10.1 m-units/l) there were greater
      cardiac responses [(P < 0.001); cardiac output, 1.17 +/- 0.36 l/min, and heart
      rate, 13.4 +/- 2.1 beats/min], and a larger fall in systemic vascular resistance
      and superior mesenteric artery vascular resistance. Unlike the high fat meal
      alone, the high fat meal with insulin was accompanied by a fall in calf vascular
      resistance (8.3 +/- 3.3 units) and blood pressure (3.8 +/- 1.6 mmHg). 4. The
      results of this study support a role for insulin in modulating postprandial
      cardiovascular homoeostasis; in particular, by its depressor action on skeletal
      muscle vasculature, insulin may in part contribute to the fall in blood pressure
      seen in the elderly, who have an inadequate cardiac response to the fall in
      systemic vascular resistance occurring after meal ingestion.

PMID- 8983867
TI  - Effects of adrenaline infusion on the interstitial environment of subcutaneous
      adipose tissue as studied by microdialysis.
AB  - 1. Adrenaline was infused at a rate of 25 ng min-1 kg-1 into seven healthy
      volunteers and its effects on adipose tissue were studied by microdialysis. 2.
      Adrenaline infusion led to a rapid rise in plasma adrenaline concentration from a
      basal value of 0.15 +/- 0.03 nmol/l to a peak value of 1.82 +/- 0.15 nmol/l
      within 30 min (analysis of variance: P < 0.001). Plasma noradrenaline levels
      increased from the basal value of 1.48 +/- 0.21 nmol/l to 1.78 +/- 0.20 nmol/l
      within 30 min of infusion (analysis of variance: P < 0.05). Once the infusion was
      stopped the plasma adrenaline and noradrenaline levels returned to basal values
      within 15 min. 3. The arterialized blood glycerol concentration increased from
      the basal value of 47 +/- 6 mumol/l to 101 +/- 8 mumol/l (analysis of variance: P
      < 0.001), and the interstitial glycerol concentration increased from 181 +/- 17
      mumol/l to 350 +/- 47 mumol/l (analysis of variance: P < 0.001) within 30 min of
      adrenaline infusion. Thereafter the concentrations declined gradually towards
      basal values. When the infusion was discontinued the levels declined further,
      below the basal value. 4. Adrenaline infusion caused a significant increase in
      the plasma glucose and blood lactate concentration (analysis of variance: P <
      0.001 and P < 0.001), but no such effect was observed in the interstitial
      concentrations. 5. The basal dialysate concentrations of adrenaline and
      noradrenaline were 43 +/- 37 pmol/l and 1170 +/- 430 pmol/l respectively. There
      were difficulties in estimating the absolute interstitial concentrations of
      adrenaline and noradrenaline which are discussed. The dialysate adrenaline
      concentration increased to a peak value of 112 +/- 48 pmol/l (analysis of
      variance: P < 0.05) within 30 min. The dialysate noradrenaline concentration
      increased to a peak value of 2830 +/- 1470 pmol/l, but the rise was not
      significant. 6. These results show that the interstitial concentrations of
      metabolites and hormones can be significantly different from those of blood and
      plasma and these differences reflect tissue specialization.

PMID- 8983868
TI  - Augmented thermic effect of amino acids under general anaesthesia occurs
      predominantly in extra-splanchnic tissues.
AB  - 1. Intravenous infusion of amino acid mixtures stimulates human oxidative heat
      production more effectively under general anaesthesia than in the unanaesthetized
      state. To analyse the splanchnic and extra-splanchnic regional distribution of
      this stimulation, whole body and splanchnic oxygen uptake, blood flow and blood
      temperatures were measured by a catheterization technique in 14 patients
      undergoing isoflurane anaesthesia for abdominal surgery. During the anaesthesia
      period, a mixture of 19 amino acids (240 kJ/h) was infused intravenously into
      seven of the patients while the others served as controls, receiving isovolumic
      infusions of a nutrient-free saline solution. 2. Whole body oxygen consumption
      fell by approximately 40% during anaesthesia and surgery in the controls.
      Approximately 80-95% of the reduction occurred in the extra-splanchnic tissues.
      The splanchnic oxygen uptake fell by 31 +/- 6% in the controls during the initial
      phase of anaesthesia, after which it returned to the pre-anaesthesia level. The
      initial reduction of the controls' splanchnic oxygen consumption accounted for
      only approximately 23% of the simultaneous anaesthesia-induced reduction in
      pulmonary oxygen uptake. No initial reduction of the splanchnic oxygen uptake was
      observed in the patients treated with amino acid. 3. The amino acid infusion
      stimulated the whole body oxidative heat production by approximately 18 W during
      anaesthesia and surgery and by approximately 70 W at the emergence from
      anaesthesia. Approximately 74% of the stimulation occurred in the extra
      splanchnic tissues. At awakening, the splanchnic oxygen uptake rose to
      approximately 64% above the pre-anaesthesia level in the amino acid group. 4.
      During the entire period of anaesthesia, the whole body heat content fell by 282
      +/- 68 kJ in the controls and by 57 +/- 25 kJ in the amino acid group. Amino acid
      treatment thus prevented approximately 80% of the anaesthesia-induced reduction
      in whole body heat content. 5. During anaesthesia and surgery, cardiac output was
      approximately 25% and approximately 16% below the baseline, preanaesthesia levels
      in the control and amino acid groups, respectively. At awakening, it rose to
      approximately 44% above baseline in the amino acid group while in the controls it
      remained unchanged. In both groups the splanchnic blood flow was unaffected by
      anaesthesia or by amino acid infusions.

PMID- 8983869
TI  - Time course study of oxidative stress in aorta and heart of diabetic rat.
AB  - 1. Oxygen free radicals have been suggested to be a contributory factor in
      complications of diabetes mellitus. In the present study, we investigated the
      lipid peroxide level [thiobarbituric acid-reactive substances (TBARS)] and
      activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione
      peroxidase) in aorta, heart and blood of control and streptozotocin-induced
      diabetic rats at various stages of development of diabetes (0 to 6 weeks). 2.
      There was no change in the TBARS levels of aorta, heart and blood in the control
      group. A significant (P < 0.05) increase in TBARS levels of aorta, heart and
      blood was observed in the diabetic group. 3. There were no significant changes in
      the activities of superoxide dismutase, catalase and glutathione peroxidase in
      the aorta, heart and blood of control rats at all time intervals. In the diabetic
      group, there was a significant (P < 0.05) increase in the activity of superoxide
      dismutase and glutathione peroxidase in aorta from the fourth week onwards while
      the activity of catalase increased at all time intervals. In the heart of
      diabetic rats, the activity of total superoxide dismutase and Cu-Zn-superoxide
      dismutase increased significantly (P < 0.05) from the second week onwards while
      activity of Mn-superoxide dismutase decreased at the fourth week and increased at
      the sixth week. The activity of catalase and glutathione peroxidase increased
      significantly (P < 0.05) at all time intervals. In the blood, the activity of
      superoxide dismutase and glutathione peroxidase increased from the third week
      while catalase activity increased from the fourth week. 4. The present findings
      suggest that oxidative stress starts at early onset of diabetes mellitus and
      increases progressively.

PMID- 8983870
TI  - Phenolic content of various beverages determines the extent of inhibition of
      human serum and low-density lipoprotein oxidation in vitro: identification and
      mechanism of action of some cinnamic acid derivatives from red wine.
AB  - 1. An antioxidant effect of phenolic substances in red wine to reduce
      oxidizability of low-density lipoprotein has been proposed as the basis for a
      relatively lower incidence of coronary disease in populations with high red wine
      intake. We have now investigated the possible antioxidant effects of various
      beverages, including red wines, white wines, beers and red grape juices (diluted
      1:500), on metal ion-dependent (copper) and -independent (aqueous peroxyl
      radicals) oxidation of isolated human low-density lipoprotein. We also tested the
      effects of these beverages on copper-initiated oxidation of lipoproteins in
      serum. 2. The higher the polyphenolic content of a beverage, the greater was its
      antioxidative effect measured as change in lag time in the different oxidation
      systems. Upon stripping the polyphenolics from the drinks, the lag times returned
      to control levels in isolated low-density lipoprotein; however, the low
      concentrations of phenolics remaining after stripping had a lesser but still
      significant effect on oxidation of lipoproteins in serum. The inhibitory effect
      of these phenolics appeared to be more pronounced for metal ion (copper)-induced
      oxidation than for those induced by aqueous peroxyl radicals, suggesting that
      both copper-binding and free radical-trapping activities may be involved. A
      mixture of the carboxylic acids representative of those present in red wine
      exhibited no significant effect on lag time of metal ion-dependent and 
      independent low-density lipoprotein oxidations. Ethanol, at concentrations of 0.1
      0.5%, had no effect on either copper-induced or aqueous peroxyl radical
      oxidations. 3. Extracts of acid-hydrolysed red wine were separated by thin-layer
      chromatography and the most active antioxidant fractions identified. GC-MS and
      HPLC analysis of these fractions resulted in the identification of several
      cinnamic acid derivatives, such as coumaric acid, caffeic acid and protocatechuic
      acid. Dose-response studies using the pure compounds indicated that caffeic acid
      was the most active antioxidant with an IC50 < 1 mumol/l for copper-initiated low
      density lipoprotein oxidation. Caffeic acid (1 mumol/l) significantly inhibited
      lipid hydroperoxide formation while sparing alpha-tocopherol consumption. Caffeic
      acid at the same concentration also inhibits aqueous peroxyl radical-induced
      oxidation of low-density lipoprotein, sparing alpha-tocopherol. There was no
      evidence of caffeic acid preventing the binding of copper to low-density
      lipoprotein. 4. We conclude that phenolics in both alcoholic and non-alcoholic
      beverages can give dose-dependent protection against oxidation of low-density
      lipoprotein. Caffeic acid and protocatechuic acid are two compounds likely to
      contribute to these effects. These findings may be relevant to the putative
      cardiovascular-protective effects of high phenolic content alcoholic beverages
      such as red wine; however, the widespread occurrence of antioxidants such as
      caffeic acid in fruits and vegetables suggests that these protective principles
      are not limited to red wine.

PMID- 8983871
TI  - Suppression of oxidant production by diltiazem, nifedipine and verapamil in human
      neutrophils.
AB  - 1. Polymorphonuclear leucocytes are a major source of toxic oxidants in vivo,
      causing tissue injury in certain circumstances such as ischaemia and reperfusion.
      Calcium ions are a key mediator in the production of oxidants by these cells. The
      aim of this study was to examine the effects of the widely used calcium
      antagonists diltiazem, nifedipine and verapamil on the production of oxidants in
      neutrophils. 2. Human neutrophils were freshly prepared, suspended in different
      luminol media and mixed with varying amounts of each calcium antagonist. They
      were then stimulated with either serum-opsonized zymosan or phorbol 12-myristate
      13-acetate. Oxidant production was determined by three methods, namely luminol
      enhanced chemiluminescence, oxygen consumption and cytochemical staining. 3.
      Calcium antagonists inhibited oxidant production by neutrophils. IC50 values for
      diltiazem, nifedipine and verapamil in calcium-free medium were 0.32 mmol/l (SEM
      0.02), 0.27 mmol/l (SEM 0.02) and 0.24 mmol/l (SEM 0.02) respectively under
      zymosan stimulation, and 0.33 mmol/l (SEM 0.02), 0.26 mmol/l (SEM 0.02) and 0.13
      mmol/l (SEM 0.07) respectively under phorbol 12-myristate 13-acetate stimulation.
      These effects were independent of the presence of Ca2+ in the extracellular
      solution. Some inhibition was also observed when the calcium antagonists were
      added during the course of a respiratory burst. Oxygen uptake by the cells was
      reduced in the presence of each calcium antagonist. Phagocytosis by the
      stimulated neutrophils was not affected despite inhibition of oxidant production.
      4. We conclude that calcium antagonists can suppress the capacity of neutrophils
      to produce oxidants. This result may provide a novel explanation for the
      observation that delayed treatment with calcium antagonists may attenuate post
      ischaemic myocardial dysfunction.

PMID- 8983872
TI  - Effect of treatment with calcium antagonists in vitro and in vivo on the
      contractile response of isolated rat and human detrusor muscle.
AB  - 1. The effect of calcium antagonists on the contractile response of human and rat
      isolated detrusor muscle in vitro was investigated. The effect of treatment with
      nimodipine on rat detrusor muscle in vivo was also examined. 2. Nimodipine 0.1
      mumol/l, nifedipine 0.1 mumol/l, nifedipine 0.25 mumol/l and verapamil 1.5
      mumol/l reduced the maximum contractile response of isolated human detrusor
      muscle to carbachol by 42%, 35%, 41% and 28% respectively (P < 0.01). Verapamil
      0.1 mumol/l had no significant effect on contractile response. 3. Nimodipine 0.1
      mumol/l reduced the maximum contractile response of isolated rat detrusor muscle
      in vitro to electrical field stimulation and carbachol by 53% and 84%
      respectively (P < 0.01). 4. Rats were pretreated with nimodipine for 8 days (5 mg
      day-1 kg-1) or with a single dose. Serum nimodipine concentrations were higher in
      rats treated for 8 days. In rats treated with nimodipine for 8 days there was no
      significant difference in detrusor contractile response compared with controls.
      However, after one dose of nimodipine the maximum contractile response was
      significantly reduced compared with controls (P < 0.05). 5. At the concentrations
      studied, nimodipine had a greater inhibitory effect on the contractile response
      of isolated human detrusor muscle. Nimodipine significantly reduced the
      contractile response of rat detrusor muscle in vitro and after a single dose in
      vivo, but had no significant effect after 8 days' treatment in vivo. It is
      possible that chronic oral treatment with nimodipine caused an up-regulation of
      1,4-dihydropyridine-sensitive calcium channels, which may explain the lack of
      clinical effect of chronic treatment with calcium antagonists in patients with
      detrusor instability.

PMID- 8983873
TI  - Mitochondrial protein content and in vivo synthesis rates in skeletal muscle from
      critically ill rats.
AB  - 1. Recently we reported decreased activities of two mitochondrial marker enzymes
      (citrate synthase and cytochrome c oxidase) in skeletal muscle from a rat model
      of critical illness (zymosan injection). In the present study we investigated (i)
      whether these decreases in enzyme activity reflect a reduction in mitochondrial
      content and (ii) whether this potential reduction in mitochondrial content was
      the result of decreased mitochondrial protein synthesis rates. 2. Mitochondrial
      protein content was calculated from the activities of cytochrome c oxidase in
      whole-muscle homogenates and purified mitochondria. Synthesis rates of
      mitochondrial protein in vivo were studied by measuring the incorporation of
      [3H]phenylalanine into mitochondrial protein using the flooding dose technique.
      3. Mitochondrial protein content was reduced to 54% of that measured in the pair
      fed rats and to 71% of that measured in control rats fed ad libitum 2 days after
      the zymosan treatment. The decreased mitochondrial protein content observed 2
      days after zymosan challenge was preceded by a reduced rate of synthesis of
      mitochondrial protein 16h after treatment. Both changes were of greater magnitude
      than the general muscle wasting and the decreased rate of synthesis of mixed
      protein observed in the zymosan-treated rats. 4. We conclude that the acute phase
      of critical illness in zymosan-treated rats is characterized by a substantial
      reduction in muscle mitochondria that is at least in part caused by a decreased
      rate of synthesis of mitochondrial protein. This derangement in mitochondrial
      protein metabolism may be related to the impaired muscle function observed during
      and after critical illness.

PMID- 8983874
TI  - Validation of the supine venous pump function test: a new non-invasive tool in
      the assessment of deep venous insufficiency.
AB  - 1. A new non-invasive test was developed to assess calf muscle pump function: the
      supine venous pump function test. The technique uses strain-gauge plethysmography
      and is performed in the supine position. The method is superior to other non
      invasive methods because basically the most essential haemodynamic parameter,
      venous pressure decrease, is used by properly converting venous volume
      measurements into venous pressure. The validity of this test was established by
      comparison with invasive venous pressure measurements and by determining the
      reproducibility. Additionally, normal values were determined. 2. In 28
      extremities the supine venous pump function test was performed simultaneously
      with invasive venous pressure measurements. The reproducibility of the test was
      assessed in 10 randomly chosen volunteers. In 34 volunteers normal values were
      obtained and 26 patients with clinical venous insufficiency were examined. 3.
      Comparison of the two methods revealed a correlation coefficient of r = 0.98 (P <
      0.001). A mean difference of 3.9%pf between both methods was found with limits of
      agreement of -6.3%pf to 14.1%pf. The coefficient of repeatability was 13%pf and
      the coefficient of variation was 9%. The normal range was found to be > 60%pf.
      The mean pump function in the patient group was 45%pf. 4. The limits of agreement
      are small enough to be confident that the supine venous pump function test can be
      used instead of invasive venous pressure measurements to assess calf muscle pump
      function in clinical practice. The reproducibility of the test is good.

PMID- 8983875
TI  - Renal effects of amino acids and dopamine in renal transplant recipients treated
      with or without cyclosporin A.
AB  - 1. The nephrotoxic effects of cyclosporin A may diminish the ability of the
      transplanted kidney to increase the glomerular filtration rate and effective
      renal plasma flow during infusion of dopamine or amino acids. 2. The present
      study included 16 renal transplant recipients transplanted for more than 6
      months. Eight of the patients were on immunosuppressive treatment including
      cyclosporin A [cyclosporin A group; cyclosporin A dose, 2.7 +/- 0.4 mg/kg; S
      creatinine, 105 +/- 12 mumol/l (means +/- SEM)], whereas eight patients had never
      received cyclosporin A (non-cyclosporin A group; S-creatinine, 89 +/- 6 mumol/l).
      The renal response to infusion of dopamine and of amino acids was investigated on
      two separate days. All clearance measurements were carried out at nadir
      cyclosporin A blood levels. 3. Effective renal plasma flow increased
      significantly in the non-cyclosporin A group and cyclosporin A group by 31.0 +/-
      4.1% and 35.9 +/- 6.6%, respectively, during infusion of dopamine, and by 18.7 +/
      6.7% and 13.9 +/- 5.3%, respectively, during infusion of amino acids. Glomerular
      filtration rate increased significantly in the non-cyclosporin A group and
      cyclosporin A group by 15.7 +/- 3.3% and 18.3 +/- 4.7%, respectively, during
      infusion of dopamine, and by 18.9 +/- 4.5% and 15.0 +/- 3.7%, respectively,
      during infusion of amino acids. 4. Furthermore, the amino acid- and dopamine
      induced increases in proximal tubular outflow (renal clearance of lithium) and
      calculated changes in renal proximal and distal tubular handling of sodium (and
      water) were comparable between the two groups of patients. Dopamine caused
      significant natriuresis in both groups. 5. In conclusion, low-dose cyclosporin A
      seems not to attenuate the renal haemodynamic and tubular response to infusions
      of amino acids and of dopamine in renal transplant recipients with a good graft
      function.

PMID- 8983876
TI  - Chronic sodium-potassium-ATPase inhibition with ouabain impairs renal
      haemodynamics and pressure natriuresis in the rat.
AB  - 1. Chronic Na+, K(+)-ATPase inhibition with ouabain induces hypertension in the
      rat. To examine the role of the kidney in this process, the effect of changes in
      renal perfusion pressure on glomerular filtration rate, renal blood flow and
      urinary sodium excretion were determined in rats treated intraperitoneally with
      ouabain (27.8 micrograms day-1 kg-1 body weight) or vehicle for 6 weeks. 2. After
      ouabain administration, baseline mean arterial pressure was significantly higher
      (P < 0.05) in ouabain-treated rats (151 +/- 2 mmHg; n = 9) than in control rats
      (116 +/- 4 mmHg; n = 8). 3. At equivalent renal perfusion pressures, glomerular
      filtration rate was significantly lower (P < 0.05) in ouabain-treated rats
      compared with control rats. Glomerular filtration rate was 721 +/- 73
      microliters/min at 150 mmHg, and fell significantly to 322 +/- 64 microliters/min
      at 100 mmHg. In the control group, glomerular filtration rate was well
      autoregulated. The glomerular filtration rate autoregulatory index was calculated
      to determine the ability to maintain glomerular filtration rate during changes in
      renal perfusion pressure (0 reflects perfect autoregulation; > 1 reflects the
      absence of autoregulation). This index was greater in the ouabain group than in
      the control group (1.54 +/- 0.2 compared with 0.29 +/- 0.2; P < 0.05). Renal
      blood flow showed a similar pattern. 4. Absolute urinary sodium excretion rate
      was less in ouabain-treated rats than in control rats at equivalent renal
      perfusion pressures. The slope of the relationship between absolute urinary
      sodium excretion rate and renal perfusion pressure was greater (P < 0.05) in the
      control group than in the ouabain group (309.1 +/- 57.1 compared with 82.1 +/-
      14.8 mumol min-1 mmHg-1). 5. Thus, chronic inhibition of Na+,K(+)-ATPase induces
      less efficient autoregulation of glomerular filtration rate and renal blood flow
      as well as a rightward shift in the pressure natriuresis relationship, such that
      a 25-30 mmHg higher renal perfusion pressure is necessary to excrete any given
      sodium load. These abnormalities may contribute to the development and
      maintenance of hypertension in this model.

PMID- 8983877
TI  - Comparison of the mitogenic activity of human epidermal growth factor I-53 and
      epidermal growth factor I-48 in vitro and in vivo.
AB  - 1. Epidermal growth factor is secreted into the gut lumen as a 53 amino acid
      peptide in vivo. Several preliminary studies have examined the clinical benefit
      of recombinant epidermal growth factor in intestinal disease, but there is
      inconsistency in the form of epidermal growth factor used (some using epidermal
      growth factor 1-48 and some epidermal growth factor 1-53), making comparisons
      difficult to evaluate. 2. We therefore examined the relative potency of
      recombinant epidermal growth factor 1-48 and epidermal growth factor 1-53 in
      stimulating [3H]thymidine uptake into primary rat hepatocytes at various doses in
      vitro and on various parameters of proliferation within the gastrointestinal
      tract when infused intravenously at 50 nmol day-1 kg-1 into rats receiving total
      parenteral nutrition. 3. Epidermal growth factor 1-53 was about twice as potent
      as epidermal growth factor 1-48 in its ability to stimulate [3H]thymidine
      incorporation into rat hepatocytes in vitro. In vivo studies supported this
      finding as, in both the small and large intestine, epidermal growth factor 1-53
      caused about a 30% greater stimulation of intestinal growth than epidermal growth
      factor 1-48 (P < 0.001). 4. The 1-48 truncated form of epidermal growth factor is
      less active than the full-length molecule in vitro and in vivo. This must be
      borne in mind when comparing clinical trials that use different forms of
      recombinant epidermal growth factor.

PMID- 8983878
TI  - Plasma arachidonic acid-rich phospholipids in Crohn's disease: response to
      treatment.
AB  - 1. Increased concentrations of plasma polyunsaturated fatty acids have been
      implicated in the pathogenesis of Crohn's disease. However, it is not known
      whether there are corresponding changes in circulating phospholipids--the major
      source of fatty acids in the plasma. 2. Fasting plasma samples were obtained from
      17 control subjects and 13 patients with active Crohn's disease [Simple Index of
      Crohn's Disease Activity (SICDA) > 6] before, and 2 and 8 weeks after, treatment
      with either a peptide diet or oral prednisolone. 3. Before treatment, the Crohn's
      disease patients had mildly active disease (SICDA 9.9 +/- 0.8, erythrocyte
      sedimentation rate 26.4 +/- 6.5 mm/h, serum C-reactive protein 2.8 +/- 0.4 mg/l).
      The proportions of the polyunsaturated phosphatidylcholine species, 16:0-20:4
      (10.0 +/- 0.7%) and 16:0-22:6 (7.1 +/- 0.8%), were both significantly higher than
      those in healthy controls (7.6 +/- 0.5%, P < 0.01 and 5.3 +/- 0.5%, P < 0.05
      respectively). 4. After 2 weeks treatment, the SICDA in the Crohn's disease
      patients decreased to 3.2 +/- 0.6 (P < 0.0001 compared with the pretreatment
      value), and there were corresponding falls in the erythrocyte sedimentation rate
      (to 12.6 +/- 2.7 mm/h, P < 0.05) and C-reactive protein concentration (to 1.7 +/-
      0.3 mg/l, P < 0.05)--these improvements being maintained at 8 weeks. There was
      also a fall to normal values in 16:0-20:4 (to 7.7 +/- 0.6%, P < 0.01 compared
      with the pretreatment value) and in 16:0-22:6 (to 5.7 +/- 0.5%, P not
      significant), by week 8. 5. The proportions of polyunsaturated
      phosphatidylcholine molecular species were increased in the plasma of patients
      with active Crohn's disease, but fell to normal levels during disease remission.
      These observations are consistent with the theory that, in active Crohn's
      disease, the mucosal phospholipids containing polyunsaturated fatty acids are
      increased, contribute to eicosanoid synthesis and 'spill' into the plasma.

PMID- 8983879
TI  - Effect of sustained inspiratory loading on respiratory sensation and CO2
      responsiveness in normal humans.
AB  - 1. To examine the effects of sustained resistive loading on the relationship
      between inspiratory effort sensation and respiratory drive (P0.1) and to
      determine if the change in CO2 responsiveness after sustained loading is
      accompanied by altered effort perception, hypercapnic responses were measured
      before, immediately after and 15 min after sustained resistive loading in seven
      subjects (six men, one woman). Sustained resistive loading was set to exceed a
      diaphragm tension-time index of 0.2. 2. Mean time to task failure during
      sustained loading was 17.7 min (range 12.5-22.5 min). The mean inspiratory effort
      sensation score rose from 3.4 (SEM 0.8) to 8.1 (0.8), whereas P0.1 fell from 29.5
      (3.6) to 18.1 (3.6) cmH2O. 3. Immediately after loading the slopes of the
      ventilatory and sensory responses to CO2 fell (ventilatory response: before
      loading 16.7 (2.4) lmin-1kPa-1, immediately after loading 7.88 (2.18)lmin-1kPa-1;
      sensory response: before loading 1.95 (0.38) units/kPa; immediately after loading
      1.12 (0.38) units/kPa; P < 0.05. Changes reverted to preloading levels by 15 min.
      4. Sustained loading can lead to a dissociation between respiratory drive, as
      reflected by P0.1, and inspiratory effort sensation, and this disturbance can
      persist once the load is removed. Impaired sensory perception may be the primary
      determinant of the change in CO2 responsiveness seen after sustained resistive
      loading.

PMID- 8983880
TI  - Blood transfusion enhances production of T-helper-2 cytokines and transforming
      growth factor beta in humans.
AB  - 1. Blood transfusion confers immune suppression with improved allograft survival.
      The aim of this study was to evaluate the effect of blood transfusion on the
      production of T-helper-2 cytokines and transforming growth factor beta, which are
      associated with suppression of allograft rejection. An additional aim was to try
      to identify which blood cell type is mostly responsible for the blood transfusion
      effect. Production of interleukin-4, interleukin-10 and transforming growth
      factor beta by peripheral blood mononuclear cells isolated from patients with end
      stage renal disease was measured in vitro. These assays were performed before,
      and 4h, 4, 7 and 14 days after a single blood transfusion and the transfusion of
      one unit of leucocyte-free erythrocytes. 2. Blood transfusion stimulated a
      significant rise in the production of all three cytokines measured. Transfusion
      of erythrocytes had no effect on the production of interleukin-4 or interleukin
      10. 3. It is suggested that blood transfusion enhances the production of
      interleukin-4, interleukin-10 and transforming growth factor beta. These
      cytokines may inhibit production of T-helper 1 and pro-inflammatory cytokines,
      deactivate cytotoxic cells and thereby suppress allograft rejection. It is
      further suggested that the leucocyte is the transfused cell type which is mostly
      associated with induction of this immunosuppressive response.

PMID- 8983881
TI  - Adrenomedullin: correction.

PMID- 8983882
TI  - In vitro and in vivo antibacterial activities of clarithromycin.
AB  - The in vitro and in vivo antibacterial activities of clarithromycin (CAM), a new
      oral macrolide antibiotic, were compared with those of erythromycin (EM),
      josamycin (JM) and rokitamycin (RKM). The antibacterial spectrum and in vitro
      activities of CAM were similar to those of EM. Therapeutic efficacies of CAM
      against various experimental infections in mice--including systemic infections
      caused by gram-positive bacteria such as Staphylococcus aureus, Streptococcus
      pyogenes and Streptococcus pneumoniae, and subcutaneous abscess due to S. aureus,
      and bacterial pneumonia caused by S. pneumoniae--were superior to those of EM, JM
      and RKM. CAM exhibited higher serum levels than EM in mice after a single oral
      dose of 50 mg/kg.

PMID- 8983883
TI  - Comparison of the bactericidal action of amikacin, netilmicin and tobramycin in
      free and liposomal formulation against Pseudomonas aeruginosa.
AB  - The rates at which free, cationic and anionic liposomal forms of amikacin,
      netilmicin and tobramycin kill Pseudomonas aeruginosa were studied in vitro.
      Control inocula with no antibiotic yielded 6.76, 9.53 and 9.74 log CFU/ml at 0, 6
      and 24 h, respectively. Empty anionic or cationic liposomes had no effect on
      bacterial growth. The killing rates of free antibiotics against the bacterial
      strain were not enhanced by the addition of either empty anionic or cationic
      liposomes. After 6 and 24 h of exposure at 1, 2 and 4 times the minimum
      inhibitory concentrations, free amikacin, netilmicin and tobramycin demonstrated
      a more rapid bactericidal effect than encapsulated anionic or cationic liposomes.
      The killing rates of liposomal aminoglycosides were lower than those of free
      aminoglycosides at identical concentrations, suggesting that only fractions of
      the encapsulated drugs were released from liposomes.

PMID- 8983884
TI  - Effect of subinhibitory concentrations of ceftazidime, ciprofloxacin, and
      azithromycin on the hemagglutination and adherence of uropathogenic Escherichia
      coli strains.
AB  - The effect of subinhibitory concentrations (sub-MICs) of ceftazidime,
      ciprofloxacin, and azithromycin on the hemagglutination (HA) and adherence
      ability of 29 P-fimbriated Escherichia coli strains to the buffalo green monkey
      kidney (BGMK) cell line was investigated. Comparisons were made between the
      values of HA titer before and those after exposure of strains to 1/2, 1/4, 1/8,
      1/16 and 1/32 MIC of antibiotics, as well as between the number of bacteria
      attached to the BGMK cells before and the number after their exposure to the same
      concentrations of antibiotics. Azithromycin at concentrations of 1/2 and 1/4 MIC
      damaged the HA capacity of the studied strains, while ceftazidime at
      concentrations of 1/2, 1/4, 1/8 and 1/16 MIC and ciprofloxacin at concentrations
      of 1/2 and 1/4 MIC increased the HA capacity of P-fimbriated E. coli. All three
      antibiotics decreased the adhesive capacity of E. coli to the BGMK cells.
      Comparing the number of adhered bacteria before and after exposure to sub-MICs of
      antibiotics, statistically significant differences were determined (p < 0.01)
      after exposure of the strains to all the concentrations of ceftazidime used after
      exposure to 1/2, 1/4, 1/8 and 1/16 MIC of ciprofloxacin, and after exposure to
      1/2, 1/4 and 1/8 MIC of azithromycin. Filaments formed by sub-MICs of ceftazidime
      and ciprofloxacin in a static experimental system caused HA, but in an
      experimental system imitating in vivo conditions, the strains adhered poorly to
      the cells.

PMID- 8983885
TI  - The influence of azithromycin on the biofilm formation of Pseudomonas aeruginosa
      in vitro.
AB  - The influence of azithromycin on biofilm formation by Pseudomonas aeruginosa, a
      cause of refractory chronic respiratory tract infection, was investigated.
      Alginic acid produced by a mucoid strain of P. aeruginosa was quantified by high
      performance liquid chromatography from colonies growing on an agar medium.
      Polysaccharides in the biofilm formed on silicon chips by a nonmucoid strain were
      determined by a tryptophan reaction. The effect of azithromycin was examined at
      concentrations below the minimum inhibitory concentration (sub-MIC) for each
      strain. Azithromycin significantly inhibited the production of alginic acid from
      the mucoid strain at > or = 1/256 MIC, and the production of exopolysaccharides
      from the nonmucoid strain at > or = 1/16 MIC. The inhibition of biofilm formation
      by azithromycin was also observed by scanning electron microscopy. These findings
      suggest that azithromycin inhibits biofilm formation by P. aeruginosa at
      concentrations well below the MIC.

PMID- 8983886
TI  - Effect of isoprinosine on 3'-Azido-3'-deoxythymidine uptake and phosphorylation
      in human peripheral blood mononuclear cells.
AB  - The effect of the immunomodulating agent Isoprinosine on AZT uptake and
      phosphorylation in human blood monocytes/macrophages was examined. AZT (1-15
      microM) uptake in monocytes/macrophages was rapid and dose- and time-dependent.
      The main metabolite formed after 1 h was AZT-5'-monophosphate. Isoprinosine
      cotreatment (5-50 microM) had no significant effect on AZT (5 microM) uptake. On
      the other hand, Isoprinosine increased the formation of AZT-diphosphate
      metabolites and, more intensively, of AZT-triphosphate (AZT-TP) metabolites after
      1 h incubation. Extended exposure (4 h) resulted in complete absence of AZT-TP
      due to dephosphorylation of these metabolites or blocking of AZT phosphorylation.

PMID- 8983887
TI  - Purpurogallin inhibits DNA synthesis of murine fibrosarcoma L-929 and human U-87
      MG glioblastoma cells in vitro.
AB  - We demonstrated, for the first time, that the flavonoid purpurogallin (PPG) at
      0.2-0.5 mM inhibits DNA synthesis of murine fibrosarcoma L-929 and human U-87 MG
      glioblastoma cells in vitro. In the human U-87 MG glioblastoma cell experiments,
      we found that when cells were incubated with PPG at 0.5 mM for 0.5 and 24 h,
      about 25 and 50% inhibition of DNA compared with control were observed
      respectively. In contrast, 0.5 mM Trolox (a more polar analogue of vitamin E) did
      not inhibit DNA synthesis in both cell lines. These data indicate that PPG
      inhibits the synthesis of DNA in two distinct tumour cell lines.

PMID- 8983888
TI  - The in vitro synergistic inhibitory effect of human amniotic fluid and gentamicin
      on growth of Escherichia coli.
AB  - The activity of serum and its synergistic effect with many antibiotics against
      bacteria are well known. Few reports are available on similar phenomena produced
      by human amniotic fluid (HAF). Thus we investigated the antibacterial activity of
      HAF and the presence of a synergistic effect with gentamicin (GM) against
      Escherichia coli strains. Antimicrobial activity was evaluated as a delay of the
      growth curve, using a turbidimetric method. E. coli ATCC 10798 and E. coli SC
      12155 were employed as test micro-organisms in nutrient broth, and GM was used at
      a subinhibitory concentration. HAF exerted antibacterial activity and,
      cooperating with GM at subinhibitory concentration, enhanced its antibiotic
      activity against E. coli. The presence of Schlievert's glycoprotein in HAF could
      explain these results.

PMID- 8983889
TI  - Meropenem permeation through the outer membrane of Pseudomonas aeruginosa can
      involve pathways other than the OprD porin channel.
AB  - The outer membrane protein (OMP) OprD is the major channel through which
      carbapenems permeate the outer membrane of Pseudomonas aeruginosa. In this study,
      we analyzed the OMP profiles of several P. aeruginosa clinical isolates showing
      diminished susceptibility to imipenem while remaining susceptible to meropenem.
      All these isolates lacked OprD or showed a reduced expression of this porin.
      Susceptibility to meropenem was thus independent of the level of OprD expression,
      indicating that the antimicrobial could be taken up via an alternative route. The
      level of expression of OprC (70 kD) was also unrelated to meropenem
      susceptibility. Nevertheless, OMPs OprF and OprE were expressed by all isolates,
      suggesting that in the absence of OprD, these porins might be involved in the
      permeation of meropenem.

PMID- 8983890
TI  - Fungemia in patients with hematologic malignancies: therapeutic effects of
      concomitant administration of fluconazole and granulocyte-colony-stimulating
      factor.
AB  - Serum (beta 1-->3)-D-glucan was elevated in 34 of 126 patients (27%) with
      hematologic malignancy who were clinically suspected of having a deep-seated
      mycosis. Although 11 patients (8.8%) were thought to have fungemia, fungi were
      isolated from blood culture in only 4. These results suggest that measurement of
      serum beta-D-glucan is useful for early diagnosis. Therapy with fluconazole
      (FLCZ) was effective in 9 of 11 patients (81.8%) suspected of having fungemia.
      Fungemia responded in 5 of 7 patients who were given granulocyte-colony
      stimulating factor (G-CSF) concomitantly with FLCZ. This result suggested that
      administration of G-CSF with FLCZ was useful therapy for fungemia, which may
      occur during granulocytopenia following chemotherapy with anticancer agents.

PMID- 8983891
TI  - A randomized trial comparing adjuvant fluorouracil, epirubicin, and mitomycin
      with no treatment in operable gastric cancer.
AB  - Combination chemotherapy (CT) has, in some groups of patients with gastric cancer
      (GC), who are at a high risk for relapse, resulted in a small but measurable
      improvement in palliation and patient survival not reaching statistical
      significance and therefore remaining applicable in an investigational setting.
      Based on the above data, we studied adjuvant CT with FEM (5-fluorouracil (5-FU),
      epirubicin, mitomycin C) in a randomized study of patients with completely
      resected stage III GC and patients with stages T1-3 with a low histologic grade.
      CT was started 2-3 weeks after surgery. From August 1988 until February 1994, 84
      patients with completely resected tumors and lymph nodes were randomized to
      either group A (FEM) or group B (no treatment). Patients were eligible for
      randomization if they had a Karnofsky score > 60, no postoperative evidence of
      residual tumor, and normal cardiac, hepatic and renal functions. Forty-two
      patients were randomized to each group, with no significant differences
      regarding: age distribution, group A 53 years (41-65), group B 57 years (35-66);
      sex, group A 32/10, group B 25/17 (men/women); site of primary tumor, group A
      22/20, group B 25/17 (pylorus/antrum); histologic grade, group A 0/19/23, group B
      0/25/17 (grades I/II/III); lymph node metastases, group A 30, group B 32, and
      surgical procedure, group A 33/9/6, group B 35/7/9 (total gastrectomy/partial
      gastrectomy/splenectomy). Group A received 5-FU 600 mg/m2/day i.v. on days 1, 8,
      29 and 36, epirubicin 45 mg/m2/day i.v. on days 1 and 29, and mitomycin C 10
      mg/m2 i.v. on day 1. The schedule was repeated every 56 days for 3 cycles. Group
      B received no treatment odd was only subjected to the regular follow-up. At the
      last follow-up at 66 months, 27/42 patients in group A (64%) had relapsed or
      died, compared to 34/42 patients in group B (81%). The differences in the relapse
      and the disease-free and the overall survival rates were not statistically
      significant. Only the subgroup of patients with histologic grade III tumors
      receiving adjuvant FEM demonstrated a trend towards improved survival (p =
      0.085). Main therapy-related toxicities for the treatment group were grade I-II
      anemia, neutropenia, and throbocytopenia in 16, 45, and 22% of patients,
      respectively, and grade I-II nausea and vomiting in 29% of patients. Based on the
      present findings and those of previous studies, even if one considers the
      difference reaching statistical significance in the latter for histologic grade
      III tumors, it becomes evident that with current therapeutic modalities adjuvant
      therapy has no established role in the management of resectable GC. Studies of
      new-generation regimens, such as FAMTX (5-FU, Adriamycin and methotrexate) as
      well as ELF (etoposide, Leucoverin, and 5-FU), should be conducted in the
      adjuvant therapy setting with a nontherapy control group, in order to clarify the
      issue of adjuvant CT in resectable GC.

PMID- 8983892
TI  - Ofloxacin once daily versus twice daily in community-acquired pneumonia and acute
      exacerbation of chronic bronchitis. A randomized multicenter study.
AB  - Eighty-two patients with community-acquired pneumonia (CAP) or acute exacerbation
      (AE) of chronic bronchitis were randomized to receive ofloxacin (OFL) 400 mg
      twice daily (39 patients) versus 400 mg once daily (43 patients) orally. Cure
      rates showed no statistically significant difference (90.1 vs. 94.6%), but more
      patients receiving 800 mg/day had side effects. Thus, the once daily
      administration of OFL is equally effective and safer than 400 mg twice daily to
      treat CAP or AE chronic obstructive pulmonary disease, especially in countries
      with higher pneumococcal and Haemophilus influenzae resistance in community
      practice.

PMID- 8983893
TI  - Multicenter randomized study of two once daily regimens in the initial management
      of community-acquired respiratory tract infections in 163 children: azithromycin
      versus ceftibuten.
AB  - In a randomized trial, we compared the efficacy and toxicity of azithromycin and
      ceftibuten once daily in the initial (empiric) therapy of proven or suspected
      community-acquired respiratory tract infections (CARTI) in 163 pediatric
      patients: 95.5% of those treated with azithromycin and 83.6% of those treated
      with ceftibuten were cured or improved. Streptococcus pneumoniae was more
      frequently eradicated in the azithromycin than in the ceftibuten group, whereas
      gram-negative bacilli were more susceptible to ceftibuten. Elimination rates for
      Staphylococcus aureus and Haemophilus influenzae were similar; adverse reactions
      did not differ in both arms. Thus, azithromycin was more effective but equally
      safe than ceftibuten in the initial therapy of pediatric CARTI.

PMID- 8983894
TI  - [Relevance of general practitioner's prescriptions for hospital pharmacotherapy.
      A survey of hospital physicians].
AB  - BACKGROUND AND OBJECTIVE: At hospital admission drugs prescribed by the general
      practitioner (GP) are often changed. This may have a negative impact on the
      relationship between family and hospital physicians as well as on the family
      doctor-patient-relationship. The study set out to examine the attitudes of
      hospital physicians towards GPs' prior ambulatory medication, especially in the
      case of drugs of unproven efficacy (e.g. certain drug combinations and
      homeopathic or herbal drugs). PARTICIPANTS AND METHODS: A total of 129 doctors of
      the surgical and medical wards of the Gottingen University Hospital received a
      standardized questionnaire focusing on drugs prescribed by referring GPs
      (response rate: 65.9%). Three case vignettes were presented describing "popular"
      GP prescriptions. Doctors of surgical and medical departments were asked whether
      or not they would follow these prescriptions. Differences in the answers between
      the groups of doctors were tested by Fisher's exact test. RESULTS: More doctors
      on the surgical than on the medical wards would usually follow GPs' medication
      (82 vs 25%; P < 0.001). According to these attitudes, more doctors of medical
      departments would stop the prescription of drug combination (82 vs 41%; P <
      0.001); both groups would be hesitant to accept homeopathic drugs (89 vs 59%; P <
      0.01) or herbal drugs (89 vs 55%; P < 0.01) as prescribed by the GP. The critical
      attitude especially of doctors of the medical departments towards drug
      combinations and herbal drugs was in line with their decision in the case
      vignettes (e.g. Capozide, Tebonin forte). CONCLUSION: Especially doctors working
      in medical departments keep in line with conventional clinical pharmacological
      criteria. If they have to decide whether or not to follow patients' ambulatory
      medication, they may overlook GPs' decision-making process underlying their
      prescribing.

PMID- 8983895
TI  - [Acute hepatitis as the leading symptom of secondary syphilis].
AB  - HISTORY AND CLINICAL FINDINGS: A 44-year-old heterosexual man reported having
      been jaundiced for 4 days. He drank little alcohol. There was no history of
      venereal disease. INVESTIGATIONS: Laboratory tests indicated marked cholestasis
      (alkaline phosphatase 1589 U/I, gamma-GT 449 U/I), but only moderately raised
      transaminases (GOT 66 U/I, GPT 230 U/I), with a bilirubin level of 4.8 mg/dl.
      Ultrasonography revealed diffuse parenchymal damage in the liver, while
      endoscopic retrograde cholangiopancreatography showed no abnormalities. Viral
      hepatitis was excluded by serological tests. Histology of a liver biopsy showed
      inflammatory infiltration of the portal areas and of the liver parenchyma.
      Routine syphilis serology indicated fresh infection with Treponema pallidum.
      There was a healing painless ulcer in the area of the sulcus coronarius of the
      genitals. TREATMENT AND COURSE: 2.4 mill. I.U. benzathine benzylpenicillin were
      administered intramuscularly. This rapidly improved his condition and liver
      function tests became normal. CONCLUSION: In case of hepatitis of uncertain
      genesis syphilis should be considered as a possible cause, even in the absence of
      other signs of the disease.

PMID- 8983896
TI  - [Differential diagnosis of berylliosis/sarcoidosis in a dental technician].
AB  - HISTORY AND CLINICAL FINDINGS: Sarcoidosis was diagnosed in a dental technician
      when he was aged 21 years. Two years later prednisolone treatment was started and
      continued for 14 years because of nonproductive cough with progressive reduction
      in vital capacity and CO transfer capacity. Subsequently the risk of exposure to
      beryllium-containing dust in dental laboratories became known. In his case
      exposure had started before sarcoidosis had been diagnosed and had continued for
      16 years. Changes typical of sarcoidosis (unproductive cough and dyspnoea;
      bihilar lymphadenopathy and reticulonodular marking in the chest radiogram) were
      now present, at the age of 40 years. INVESTIGATIONS: Vital and diffusion
      capacities were diminished, serum levels of angiotensin-converting enzyme (141
      U/I) and of neopterin (5.8 mg/l) were increased. Beryllium-lymphocyte
      transformation test of peripheral mononuclear cells after invitro culture with
      beryllium sulphate gave a raised stimulation index, and the intracutaneous
      beryllium sensitisation test was positive. This indicated sensitisation to
      beryllium even 9 years after exposure had ceased. CONCLUSION: Even after exposure
      to beryllium has ended, proof of exposure together with clinical and radiological
      findings typical of sarcoidosis and beryllium sensitisation can provide the
      diagnosis of berylliosis.

PMID- 8983897
TI  - [Diagnosis of monogenic diseases of the peripheral nervous system].

PMID- 8983898
TI  - [Morphine].

PMID- 8983900
TI  - [Use of the term "clinic" in the name of a health care establishment, Ltd.
      Decision of the Federal High Court, 6 July 1996].

PMID- 8983899
TI  - [Complications after administration of contrast media in high-risk patients. Is a
      prophylactic dialysis meaningful?].

PMID- 8983901
TI  - [Diagnosis of BSE and Creutzfeldt-Jakob disease].

PMID- 8983903
TI  - [Therapy of hypertropic obstructive cardiomyopathy].

PMID- 8983902
TI  - [Chronic myeloproliferative diseases. Erythrocyte apheresis in polycythemia
      vera].

PMID- 8983904
TI  - [Percutaneous suture closure of the femoral artery access after diagnostic heart
      catheter examination or coronary intervention].
AB  - BACKGROUND AND OBJECTIVE: Alternative methods to the conventional one of external
      compression with a pressure bandage over the site of arterial puncture after
      percutaneous catheter introduction for coronary angiography or transluminal
      balloon coronary angioplasty have failed to reduce the rate of vascular
      complications. This study was undertaken to assess the complication rate of a
      percutaneously introduced suturing device (Techstar, Perclose). PATIENTS AND
      METHODS: To achieve immediate haemostasis and thus shorten post-interventional
      immobilisation the technique of percutaneous suturing of the femoral artery was
      used in 1030 consecutive patients (793 men, 237 women; mean age 58.6 years)
      without obstructive vascular disease or local vascular complications. RESULTS:
      Percutaneous suture closure with primary haemostasis was successful after 137 of
      153 coronary angioplasties (89.5%) and after 786 of 977 left heart
      catheterisations (89.6%). Early mobilisation, after at most 4 hours, was possible
      in 923 patients with successful suture closure (89.6%). The overall complication
      rate was 0.78%. CONCLUSION: Percutaneous suture repair of the femoral artery
      after cardiac catheterisation is a safe and effective method to achieve immediate
      haemostasis. However, controlled studies are needed to demonstrate harmlessness
      of early mobilisation.

PMID- 8983905
TI  - [Sternocostoclavicular hyperostosis].
AB  - HISTORY AND CLINICAL FINDINGS: A 35-year-old previously healthy man developed a
      painful swelling in the area of the left sternoclavicular joint (SCJ),
      restricting movement. There had been no history of trauma. INVESTIGATIONS: A
      moderately increased erythrocyte sedimentation rate was the only abnormal finding
      among the usual laboratory tests. Radiologically there were marked hyperostotic
      changes in the area of the left upper thoracic cage with synostosis of the SCJ.
      Biopsy of the left clavicle showed non-specific chronic sclerosing osteomyelitis.
      TREATMENT AND COURSE: Over the next 6 years the SCJ became completely ankylosed
      and there were now extensive fibroses, some presternal and some in the upper
      mediastinum with thrombosis of the left subclavian, axillary and jugular veins
      causing inflow occlusion (Paget-von-Schroetter-syndrome). Lymph nodes in the
      region of the mandible, jugular veins bilaterally and mediastinum were noted for
      the first time, remaining unchanged in size over six months. CONCLUSION:
      Sternoclavicular hyperostosis is an important condition in the differential
      diagnosis of inflammatory or malignant processes of this joint.

PMID- 8983907
TI  - [Diagnosis of autoimmune hepatitis].

PMID- 8983906
TI  - [Periodic paralysis as the first manifestation of hyperthyroidism].
AB  - HISTORY AND CLINICAL FINDINGS: A 19-year-old man had mild diarrhoea at the time
      that suddenly one night he was unable to turn in his bed and the following
      morning could not move his arms and legs for 4 hours. Neither he nor any family
      members had previously had any paralysis. Physical examination was unremarkable
      except for mild tachycardia and first-degree goitre. INVESTIGATIONS: A
      provocation test with glucose (3 g/kg) and insulin (0.1 IU/kg) caused renewed
      paralysis for several hours, serum potassium falling from 4.3 to 3.4 mmol/l. The
      paralysis was reversed on oral potassium (40 mmol) Thyroid function tests
      revealed hyperthyroidism with an increased concentration of free thyroxine (25.5
      pg/ml) and free triiodothyronine (9.7 pg/ml), while thyroid-stimulating hormone
      was decreased (0.07 mU/I), supporting the diagnosis of autoimmune thyroiditis.
      TREATMENT AND COURSE: Thyrostatic treatment was started with thiamazole (10 mg
      every other day). There was no further periodic paralysis and another provocation
      test was negative. CONCLUSION: Fleeting paralysis is often misdiagnosed as being
      psychogenic. Potassium abnormalities are the most common cause but are only
      rarely associated with hyperthyroidism. This case of thyrotoxic hypokalaemic
      paralysis was probably based on a genetic defect of muscle fibre membrane
      manifesting itself only in the presence of hyperthyroidism.

PMID- 8983908
TI  - [The prostate-specific antigen in the early recognition of prostate carcinoma].

PMID- 8983909
TI  - [Neuroprotective therapy of Alzheimer's disease?].

PMID- 8983910
TI  - [Clinical value of laminin determination in progressive liver cirrhosis].

PMID- 8983911
TI  - [Progress and perspectives in palliative therapy of breast carcinoma].

PMID- 8983912
TI  - Overview of allergic mechanisms. Ebastine has more than an antihistamine effect.
AB  - Histamine antagonists together with topical steroids are the treatment of choice
      in allergic rhinitis. Many of these histamine antagonists exhibit effects in
      addition to blockade of the histamine receptor. In this study we have
      investigated the effects of ebastine and carebastine on the release of
      eicosanoids and cytokines from human dispersed polyp cells and the effect of
      these compounds on the release of inflammatory mediators into nasal lavage fluid
      after allergen challenge. Ebastine was shown to block the release of anti-IgE
      induced prostaglandin D2 (PGD2) and leukotriene C4/D4 from human nasal polyp
      cells (IC30 values of 2.57 and 9.6 mumol/L, respectively) and to inhibit the
      release of cytokines. Carebastine inhibited the release of PGD2 (IC30 8.14
      mumol/L) but had little effect on cytokine release. When patients underwent nasal
      provocation tests with allergen, ebastine significantly increased the mean number
      of pollen grains required to induce an allergic response. In addition, the drug
      inhibited the release of granulocyte-macrophage colony-stimulating factor but had
      no effect on any other mediators measured.

PMID- 8983913
TI  - Effect of exposure to oxygen at 101 and 150 kPa on the cerebral circulation and
      oxygen supply in conscious rats.
AB  - Hyperbaric oxygen at pressures of 300 to 500 kPa has been shown to induce changed
      distribution of cerebral blood flow (QCBF) in rats, in places reducing the supply
      of the supplementary O2. Thus, in the present study, the effect of hyperoxia at
      101 (group 1, n = 9) and 150 (group 2, n = 9) kPa O2 on cerebral blood flow
      distribution and central haemodynamics was tested in conscious, habituated rats.
      During the control period the systolic arterial pressure (BPs), heart rate (fc),
      breathing frequency (fb), cardiac output (Qc), arterial acid-base chemistry and
      glucose, as well as QCBF distribution (rQCBF) were similar in the two groups of
      animals. During O2 exposure, the acid-base chemistry remained unchanged. The
      haemoglobin decreased in group 2, but remained unchanged in group 1. The fc
      decreased rapidly in both groups during the change in gas composition, after
      which fc remained constant both in group 1 and in group 2, for whom pressure was
      increased. The Qc and fb decreased and BPs increased similarly in the two groups.
      Total QCBF and rQCBF decreased to the same extent in both groups, and the rQCBF
      changes were equally scattered. In group 1, breathing of pure O2 did not increase
      the O2 supply to any cerebral region except to the thalamus and colliculi after
      60 min, whereas the O2 supply to the hypothalamus decreased and remained low. In
      group 2, the O2 supply was unchanged compared to the control period in all
      regions. These findings agree with previous observations during exposures to
      higher O2 pressures. In air after O2 exposure the acid-base chemistry remained
      normal. The fc and fb increased to higher levels than during the control period.
      The BPs remained high. The brain blood flows were increased, inducing elevated O2
      supply to several brain regions compared to the control period. In conclusion, O2
      supply to the central nervous system was found to be in the main unchanged during
      breathing of O2 at 101 kPa and 150 kPa.

PMID- 8983914
TI  - Influences of handgrip on shoulder muscle activity.
AB  - Four shoulder muscles (the supraspinatus, the infraspinatus, the middle portion
      of the deltoid and the descending part of the trapezius muscle) were examined
      using electromyography (EMG) in abducted and flexed arm positions, in nine
      subjects who had no history of illness from arm or shoulder. The subjects were
      asked to supply an intermittent isometric handgrip force of 30% and 50% of
      maximal voluntary contraction, in a total of eight different arm positions. The
      EMG activity with and without hand activity was compared in all positions. There
      was a statistically significant increase in the EMG activity in the supraspinatus
      muscle in humeral flexion from and above 60 degrees. In the infraspinatus muscle
      the changes were less; a significant decrease was however noticed in abduction.
      In the deltoid muscle there was a significant decrease with hand activity in
      flexion from and above 90 degrees. There was no statistically significant
      alteration regarding the EMG activity of the trapezius muscle. The result of this
      study implies that high demands on handgrip force, particularly while using hand
      tools in elevated arm positions, adds further to the already high load on some
      shoulder muscles. This factor should be considered in the design of manual work
      and in the places of work.

PMID- 8983915
TI  - Effects of psychophysiological stress on trapezius muscles blood flow and
      electromyography during static load.
AB  - Mental stress was induced by the Stroop colour word task (CW task) and the
      effects on the microcirculation and electromyography (EMG) in the upper portion
      of the trapezius muscle were studied during a series of fatiguing, standardized
      static contractions. A lowered blood flow of the skin recorded continuously by
      laser-Doppler flowmetry (LDF) was used as a stress indicator in addition to an
      elevated heart rate. Muscle blood flow was recorded continuously by LDF using a
      single optical fibre placed inside the muscle, and related to surface EMG. A
      group of 20 healthy women of different ages was examined. Recordings were made
      during a 50-min period in the following sequence: a 10-min series of alternating
      1-min periods of rest and stepwise increased contraction induced by keeping the
      arms straight and elevated at 30, 60, 90 and 135 degrees with a 1-kg load carried
      in each hand; a 10-min recovery period without load; a repeated contraction
      series with simultaneous performance of the CW task; a second 10-min recovery
      period, and a second contraction series without CW task. Signal processing was
      done on line by computer. The LDF and root mean square (rms)-EMG values were
      calculated, as well as the EMG mean power frequency (MPF) for fatigue. The CW
      task added to the contraction series caused an increase in the heart rate
      accompanied by a decrease in the blood flow to the skin and a 30% increase in the
      blood flow in the exercising muscle. Both returned to normal during the
      subsequent recovery period and showed normal levels during the final contraction
      series without CW. The rms-EMG showed a 20% increase that persisted during the
      final contraction series performed without CW. There was no influence on MPF.
      This CW has previously been shown to evoke an increased secretion of adrenaline
      from the adrenal medullae to the blood. The increased blood flow in the
      exercising muscle would therefore appear to have been caused by beta-adrenoceptor
      vasodilatation, and the fall in the blood flow in the skin by alpha-adrenoceptor
      vasoconstriction. The findings may have implications for work situations
      characterized by repetitive static loads to the shoulder muscles and
      psychological stress.

PMID- 8983916
TI  - Are region-specific changes in fibre types attributable to nonuniform muscle
      hypertrophy by overloading?
AB  - Muscle fibre composition was compared among the proximal (25%), middle (50%) and
      distal (75%) regions of the muscle length to investigate whether compensatory
      overload by removal of synergists induces region-specific changes of fibre types
      in rat soleus and plantaris muscles. In addition, we evaluated fibre cross
      sectional area in each region to examine whether fibre recruitment pattern
      against functional overload is nonuniform in different regions. Increases in
      muscle mass and fibre area confirmed a significant hypertrophic response in the
      overloaded soleus and plantaris muscles. Overloading increased the percentage of
      type I fibres in both muscles and that of type IIA fibres in the plantaris
      muscle, with the greater changes being found in the middle and distal regions.
      The percentage of type I fibres in the proximal region was higher than that of
      the other regions in the control soleus muscle. In the control plantaris muscle,
      the percentage of type I and IIA fibres in the middle region were higher than
      that of the proximal and distal regions. With regard to fibre size, type IIB
      fibre area of the middle and distal regions in the plantaris increased by 51% and
      57%, respectively, with the greater changes than that of the proximal region
      (37%) after overloading. These findings suggest that compensatory overload
      promoted transformation of type II fibres into type I fibres in rat soleus and
      plantaris muscles, with the greater changes being found in the middle and distal
      regions of the plantaris muscle.

PMID- 8983917
TI  - Mitochondria changes in human muscle after prolonged exercise, endurance training
      and selenium supplementation.
AB  - The functional and structural responses to acute exercise (E) and training, (T)
      with or without selenium supplementation (Sel), were investigated in a double
      blind study on 24 young male subjects. The Sel or the placebo were given over 10
      weeks of an endurance training programme. Prior to the programme and on its
      conclusion muscle biopsies were taken from the vastus lateralis muscle before and
      after an exhausting treadmill test of maximal endurance capacity (Capmax). The
      muscle samples were examined by electron microscopy to make a quantitative
      analysis of the mitochondria population in the muscle fibres. The number of
      mitochondria per area (QA) and the relative surface occupied by the total
      mitochondria profile area (AA) were estimated. The mean area per mitochondrion
      (a) was obtained by the quotient AA/QA. The effects of the isolated or combined
      independent variables T, E and Sel were analysed by nonparametric tests. Training
      induced significant increases in both QA (30%, P < 0.001) and AA (52%, P <
      0.001), without changing a; T + Sel produced a slight rise of AA (27%, P <
      0.001), which resulted in larger (24%, P < 0.001) a. The E produced an
      enlargement of a resembling swelling. This phenomenon was also found for the
      combinations E + T and E + T + Sel, but it was then far more pronounced in E + T.
      The training effects observed are in agreement with previous descriptions. In
      contrast, the changes observed after acute exercise seem to indicate a remarkable
      short-term plasticity of muscle mitochondria. The results in Sel would seem to
      suggest a dampening effect of the selenium on the mitochondria changes, both in
      chronic and acute exercise. The mechanism of this action on mitochondrial
      turnover is uncertain, but might be related to a higher efficiency of the
      selenium-dependent enzyme glutathione peroxidase.

PMID- 8983918
TI  - Adaptation of maximal aerobic and anaerobic tests for disabled swimmers.
AB  - The purpose of the present study was to submit disabled swimmers to two maximal
      swimming tests, and by comparing the physiological and performance responses of
      disabled and normal swimmers to determine if these adapted tests can be used to
      design training programmes for this particular class of swimmer. Two groups of
      disabled (n = 8 and 6) and two groups of normal competitive swimmers (n = 9 and
      13) were respectively submitted to a functional maximal aerobic power test
      (FMAPT) and a maximal anaerobic lactic test (MANLT). For the disabled, the FMAPT
      included a slower initial speed and a slower increase in swimming speeds. In the
      maximal aerobic test, exercise duration, peak heart rate, and the maximal speed
      relative to the respective best time of a 100-m race [55.5 (SD 3.9) compared to
      56.5 (SD 2.8)%] were not significantly different between the disabled and normal
      swimmers. Peak lactate concentration was, however, higher in the disabled
      swimmers [10.8 (SD 3.5) compared to 6.8 (SD 1.6)mmol.l-1]. In the MNALT, peak
      lactate concentration [14.3 (SD 4) compared to 16.8 (SD 1.9)mmol.l-1], and the
      maximal speed relative to the respective best time in a 100-m race [99.1 (SD 3.2)
      compared to 98.3 (SD 2.5)%] were not significantly different between the disabled
      and normal swimmers. These results would seem to indicate that functional maximal
      aerobic and anaerobic field tests could be used to evaluate and design training
      programmes for disabled competitive swimmers.

PMID- 8983919
TI  - Blood lactate and pyruvate concentrations, and their ratio during exercise in
      healthy children: developmental perspective.
AB  - Blood concentrations of lactate normally increase during and after intense
      exercise as does the ratio of concentrations of lactate to pyruvate (L:P). Since
      there appear to be differences in blood lactate concentrations on exercise, in
      muscle metabolic enzyme activities, and in anaerobic capacity between children
      and adults, we speculated that there would be age related differences in lactate
      and pyruvate concentrations, and their ratio among children. Whole blood
      concentrations of lactate and pyruvate were measured in 28 healthy children aged
      7-17 years, split into three age groups: less than 11, 11-14, and 15-17 years.
      Blood was drawn at rest, immediately after 6 min of exercise at one-third and two
      thirds of maximum work capacity (Wmax), and 20 min after completion of work.
      Lactate and pyruvate concentrations increased significantly from rest to exercise
      at two-thirds Wmax [approximately 72% of peak oxygen consumption (VO2peak)].
      Whereas greater increments in lactate concentration were seen with groups of
      increasing age, exercise-related increments in pyruvate concentrations were no
      different among age groups. There was a significant rise in L:P ratio on
      exercise, with greater increments found from the youngest to the oldest group.
      There were no sex differences. We concluded that in healthy children exercising
      at approximately 70% of VO2peak there is a rise in blood lactate concentration in
      excess of that of pyruvate, such that the L:P ratio rises to a degree determined
      by age. This suggests age dependent changes, perhaps coincident with puberty, in
      pathways involved in lactate production and/or elimination.

PMID- 8983920
TI  - Role of decreased carbohydrate oxidation on slower rises in ventilation with
      increasing exercise intensity after training.
AB  - In these studies, we examined whether the rightward shift in steady-state minute
      ventilation (VE) versus O2 uptake curves after training is more closely linked to
      the reduced CO2 production from carbohydrate oxidation (CHOOX) after training
      than to the attenuated increase in blood lactate concentration. Steady state VE
      values and gas exchange were measured in eight previously sedentary men who
      underwent exercise tests of 60 W + 40 W every 6 min before and after a 9 week
      training programme of cycling approximately 40 min a day. Following training, the
      slower rises in VE with increasing exercise intensities were associated with a
      reduced reliance on CHOOX, (P < 0.01). Both before and after training, VE values
      in litres per minute rose as a linear VE = 18.CHOOX + 14, function of rates of
      CHOOX in grams per minute (r = 0.99), irrespective of a marked shift to the right
      in arterialized venous blood lactate concentration versus CHOOX curves following
      training (P < 0.01). Thus, slower increases in steady-state VE values with
      increasing exercise intensities following endurance training appeared to be more
      closely linked to the decreased reliance on CHOOX than to the attenuated increase
      in blood lactate concentration.

PMID- 8983921
TI  - Influence of the time of day on physical performance in patients with coronary
      artery disease.
AB  - The exercise training workload for cardiac patients is determined from the peak
      heart rate achieved safely during a stress test. Circadian rhythms may play a key
      role in changing physiological responses to the stress test. Therefore, the
      purpose of this study was to evaluate the influence of the time of day on
      cardiopulmonary and metabolic responses in highly trained men with coronary
      artery disease. A group of 15 patients with coronary artery disease [53.5 (SD 6)
      years] performed two sessions of graded tests to exhaustion: one session was
      performed at 10 a.m. and the second at 5 p.m. in randomized order. Treadmill
      velocity was kept constant at a speed of 4.8 km h-1 starting with an elevation of
      0% which was increased thereafter by 2.5% every 3 min. At rest the results
      revealed that only oxygen uptake was significantly lower (P < 0.05) in the
      morning compared to that observed in the evening [2.9 (SD 0.4) compared to 3.5
      (SD 0.5) ml O2.kg-1.min-1, respectively]. During exercise, differences due to
      time of day were found in the variables of maximal oxygen uptake which were
      significantly higher (P < 0.05) in the evening than in the morning [34.2 (SD 2.6)
      and 40.8 (SD 2.5) ml O2.kg-1.min-1, respectively]. These data indicated that in
      these well-trained coronary artery disease patients there was a significant time
      of day effect associated with metabolic responses following stress-testing.

PMID- 8983922
TI  - A meta-analysis of the effects of exercise and/or dietary restriction on resting
      metabolic rate.
AB  - A meta-analysis was used to examine the independent and interactive effects of
      dietary restriction, endurance exercise training and gender on resting metabolic
      rate (RMR). Sixty different group means (covering approximately 650 subjects)
      were identified from the scientific literature and subjected to meta-analysis
      techniques. Collectively (i.e., all groups combined), body weight loss was
      greater (P < 0.05) for men (approximately 18 kg) than for women (approximately 12
      kg). There were no statistically significant exercise training or gender effects
      on RMR during weight loss. Collectively (i.e., all groups combined), dietary
      restriction resulted in a -0.59 kJ.min-1 (approximately -12%) decrease in RMR (P
      < 0.05). When normalized to body weight, RMR was reduced by less than 2% (P <
      0.05). These data suggest that exercise training does not differentially affect
      RMR during diet-induced weight loss. In addition, decreases in resting metabolism
      appear to be proportional to the loss of the metabolically active tissue.

PMID- 8983923
TI  - Effects of long-term acclimatization in lowlanders migrating to high altitude:
      comparison with high altitude residents.
AB  - The physiological response to submaximal and maximal exercise was assessed in
      lowlanders and Tibetans at low (500 m above sea level) and high altitude (HA,
      3,680 m). The times spent at HA by the lowland migrators was 8 days (n = 60), 7
      months (n = 60, same group), 15 months (n = 29) and 27 months (n = 29). After the
      15-month stay at HA, the maximal oxygen uptake (VO2max) and maximal heart rate of
      the lowland migrators almost reached those of the HA native residents (Tibetans,
      n = 57), but their total work capacity and the gross efficiency (eta) of
      mechanical work remained lower than those of the Tibetans. The rate of VO2max
      achieved at 90 W by the Tibetans was lower than that of the lowland migrators. It
      was concluded that, at HA, the lowlanders regained much of the aerobic capacity
      which they had lost initially. However, they did not attain the same gross
      mechanical efficiency as the Tibetans, who seemed to be at an advantage in
      respect of work at HA.

PMID- 8983924
TI  - The topography of eccrine sweating in humans during exercise.
AB  - The purpose of this study was to investigate the distribution of steady-state
      sweating rates (msw), during stressful exercise and heat exposures. Six men
      completed 42-min trials: 2-min rest and 40-min cycling at 40% peak power in 36.6
      degrees C (relative humidity 46.0%). The msw was monitored using ventilated
      capsules at the forehead, and at three additional sites. Repeat trials allowed
      monitoring from eleven skin surfaces. Auditory canal temperature (Tac) and 11
      skin temperatures were measured. After normalising msw to the forehead response
      within subjects, differences in Tac and onset time thresholds, and transient and
      steady-state msw were examined. The pooled, lower torso msw onset [mean 45.5 (SEM
      42.0) s] preceded that of the head [mean 126.5 (SEM 34.8) s, P < 0.05], but was
      not significantly different from the legs [mean 66.6 (SEM 25.7) s], upper torso
      [mean 80.2 (SEM 36.8) s] or arms [mean 108.6 (SEM 31.2) s]. Transient msw did not
      differ among regions (P = 0.16). Mean, steady-state forehead msw [3.20 (SEM 0.51)
      mg.cm-2.min-1] was not significantly greater than the scapula, forearm, hand,
      stomach and lower back msw (in descending order), but was greater than the chest
      [1.6 (SEM 0.2)], upperarm [1.6 (SEM 0.2)], calf [1.5 (SEM 0.3)] and thigh msw
      [1.0 (SEM 0.2), P < 0.05 for all comparisons]. The results did not support the
      caudal-to-rostral sweat onset evident during supine, resting heat stress.
      Equivalent Tac sweat thresholds existed between sites, while steady-state state
      msw topography varied among subjects and was not dominated by central regions.

PMID- 8983925
TI  - Ultrasonography gives directly but noninvasively elastic characteristic of human
      tendon in vivo.
AB  - To obtain an insight into tendon elasticity during human movement, a real-time
      ultrasonography was applied to the contracting tibialis anterior muscle. The
      insertion point of fascicles onto the aponeurosis was clearly visualized, and its
      position relative to a fixed marker on the skin moved proximally (delta 1)
      according to the increasing dorsiflexion force (delta F) with a fixed ankle
      joint. Notably, the delta 1-delta F relationship in the tendon was found to be
      quadratic in nature (delta F = c delta 1(2); c = 1.48-2.24, r = 0.985-0.992, n =
      9) as has been reported in the isolated tendon, although the delta F-delta 1
      curves were slightly underestimated in comparison with the stiffness constant
      estimated from tendon architecture. This underestimation might be caused by
      changes in the height of the foot arch with the application of force.

PMID- 8983927
TI  - Prevention and management of thrombotic complications during coronary
      interventions. Proceedings of a conference. Sophia Antipolis, France, 16-18
      February 1995.

PMID- 8983926
TI  - Effect of end-point cadence on the maximal work-time relationship.
AB  - This study examined the effect of end-point cadence on the parameters of the work
      time relationship determined for cycle ergometry. Eight male subjects completed
      four maximal tests on an electrically-braked cycle ergometer that regulated a
      constant power output independent of cadence. The power outputs imposed ranged
      between an average of 259 W and 403 W, whereas the corresponding durations ranged
      between 139 s and 1691 s. During each test subjects were required to maintain a
      cadence of 80-90 rpm. Accumulated time to end-point cadences of 70, 60 and 50 rpm
      were recorded. The four work-time determinations for each of three end-point
      cadences were used to determine linear relationships between work and time,
      yielding both a y-intercept, which represents anaerobic work capacity, and a
      slope, which is termed critical power (CP), for each end-point cadence. There was
      a significant increase in the y-intercept as end-point cadence decreased from 70
      to 60 rpm (F[1,7] = 36.7, p < 0.001) or 70 to 50 rpm (F[1,7] = 80.1, p < 0.001),
      but not from 60 rpm to 50 rpm (F[1,7] = 3.28, p > 0.05). In contrast, there was
      no effect of end-point cadence on CP (F[2,14] = 1.89, p < 0.05). These results
      demonstrate that the end-point cadence selected to terminate tests only affects
      the y-intercept of the work-time relationship. To control for this effect, the
      cadence at which each test is terminated should be standardised if determination
      of anaerobic work capacity, as represented by the y-intercept, is required.

PMID- 8983928
TI  - Interactions between calvatic acid and related compounds with rat liver
      microsomes.
AB  - In this study we examined the interactions of liver microsomes with the
      antibiotic calvatic acid and with structural analogues, some of which had shown
      antimicrotubular properties. These drugs decreased cytochrome P-450 content
      differently according to the substitutions on the azoxy function and the
      ethoxycarbonyl derivatives were found to be the most effective ones. The decrease
      in cytochrome P-450 could be prevented by addition of cysteine or GSH, suggesting
      an involvement of sulphydryl groups. Furthermore, chromatographic analyses showed
      that ethoxycarbonyl derivatives were completely metabolized, and this would
      explain the different behaviour of these compounds towards microtubular protein
      when they were incubated with purified bovine brain protein or with liver or
      hepatoma extracts.

PMID- 8983929
TI  - Disposition of 5-formyl- and 5-methyltetrahydrofolic acid in serum after i.v.
      bolus of calcium folinate: pharmacokinetic drug interaction with preadministered
      interferon-alpha-2b.
AB  - The influence of interferon (IFN) coadministered subcutaneously with the
      biomodulating agent folinic acid on the blood serum levels of 5-formyl
      tetrahydrofolic acid (CHO-THFA) and the biotransformation into its main
      metabolite in the blood 5-methyltetrahydrofolic acid (CH3-THFA) was studied in
      patients receiving a chemotherapy with 5-fluorouracil. IFN causes a clear
      decrease of the serum concentrations of CHO-THFA and a statistically significant
      decrease of CH3-THFA concentrations (P < 0.01). The effect on serum
      concentrations could be observed in each patient, but in a different order of
      magnitude. As a consequence, the preadministration of IFN leads to a significant
      change in the basic pharmacokinetic parameters of both compounds: the mean area
      under the concentration-time curve is decreased at 27.4% for CHO-THFA (P < 0.025)
      and at 22.4% for CH3-THFA (P < 0.025), respectively. The total body clearance is
      elevated at 45.4% for CHO-THFA (P < 0.05) and at 23.4% for CH3-THFA (P < 0.05).
      The mean volume of distribution is increased by IFN at 38.2% for CHO-THFA (P <
      0.025) and at 22.3% for CH3-THFA (P < 0.05). The nearly identical mean residence
      time in both groups indicates that CHO-THFA elimination is not affected by IFN.
      But the results prove a certain interaction between IFN and CHO-THFA. IFN
      accelerates the distribution of CHO-THFA as well as of its main metabolite from
      the blood into the tissue or activates the biotransformation of CHO-THFA into CH3
      THFA inside the cells of the tissue. The extent of biotransformation of CHO-THFA
      into CH3-THFA, which takes place in the blood, is not influenced by IFN because
      percentage AUC-ratios CHO-THFA:CH3-THFA were 89.5:10.5% for the control group and
      88.8:11.2% for the IFN group.

PMID- 8983931
TI  - An attempt to predict daily erythrocyte lithium fluctuations.
AB  - Erythrocyte lithium concentration, which is a better predictor of brain lithium
      levels than plasma lithium concentrations, possesses the disadvantage of precise
      hourly determination following the last intake. The variability in RBC lithium
      accumulation increases as the extracellular lithium concentration increases. This
      increase is also time dependent and it would be very useful if the
      pharmacokinetic rate constant were known. Unfortunately, low lithium levels do
      not allow measurements within confidence intervals. In this work, we tried to
      determine, in vitro, the kinetic rate constants in erythrocytes of healthy
      volunteers. Different high lithium loaded plasma-like media were used for an
      extrapolation procedure of constants allowing the determination of an erythrocyte
      load constant namely K0 = 0.0161 +/- 0.0005 h-1 at corresponding plasma lithium
      concentrations. The abnormalities of lithium transport determined by in vitro
      procedures would be very useful in understanding the etiology of affective
      illness. Lithium flux pre-controls corrected with this rate constant would be
      very helpful in enlarging laboratory time management.

PMID- 8983930
TI  - Stereoselective pharmacokinetics of moguisteine metabolites in healthy subjects.
AB  - We studied the pharmacokinetics of moguisteine, a racemic non-narcotic peripheral
      antitussive drug, in 12 healthy male subjects after a single oral administration
      of 200 mg. The unchanged drug was absent in plasma and urine of all subjects.
      Moguisteine was immediately and completely hydrolyzed to its main active
      metabolite, the free carboxylic acid M1. Therefore, we evaluated the kinetic
      profiles of M1, of its enantiomers R(+)-M1 and S(-)-M1, and of M1 sulfoxide
      optical isomers M2/I and M2/II by conventional and stereospecific HPLC. Maximum
      plasma concentrations for M1 (2.83 mg/l), M2/I (0.26 mg/l) and M2/II (0.40 mg/l),
      were respectively reached at 1.3, 1.6 and 1.5 h after moguisteine administration.
      Plasma concentrations declined after the peak with mean apparent terminal half
      lives of 0.65 h (M1), 0.88 h (M2/I) and 0.84 h (M2/II). Most of the administered
      dose was recovered in urine within 6 h from moguisteine treatment. The systemic
      and renal clearance values indicated high renal extraction ratio for all
      moguisteine metabolites, and particularly for M1 sulfoxide optical isomers.
      Plasma concentration-time profiles and urinary excretion patterns for M1
      enantiomers R(+)-M1 and S(-)-M1 were quite similar. Thus, for later moguisteine
      pharmacokinetic evaluations the investigation of the plasma concentration-time
      curve and the urinary excretion of the sole racemic M1 through non-stereospecific
      analytical methods may suffice in most cases.

PMID- 8983933
TI  - Effects of acetysal, dexamethasone and their combination on drug metabolizing
      enzyme systems in rat liver microsomes.
AB  - After 4 days of acetysal treatment (160 mg/kg body weight orally), the following
      were established: a higher acute toxicity of acetysal, an inducing effect on
      amidopyrin N-demethylase and analgin N-demethylase activity and increases in
      cytochrome P-450 and cytochrome b5 content. Aniline hydroxylase activity
      decreased, thiopental sleeping time was prolonged and UDP-glucuronyltransferase
      activity was not changed. Dexamethasone, at a dose of 5 mg/kg body weight p.o.
      for 4 days, did not change acetysal acute toxicity but at a dose of 100 mg/kg
      i.p. increased it. Thiopental sleeping time was shortened by dexamethasone (100
      mg/kg i.p.) but was not changed by dexamethasone at 5 mg/kg p.o., alone or in
      combination. Dexamethasone at 5 mg/kg increased analgin N-demethylase and UDP
      glucuronyltransferase activities, did not change cytochrome P-450 content and
      decreased aniline hydroxylase activity. The combination with 5 mg/kg
      dexamethasone increased the activity of amidopyrin N-demethylase, analgin N
      demethylase and UDP-glucuronyltransferase and decreased those of amitriptyllin N
      demethylase and aniline hydroxylase and cytochrome P-450 content. Ethylmorphine N
      demethylase, benzphetamine N-demethylase, NADPH-cytochrome c reductase and
      glutathione S-transferase activities were not affected significantly by acetysal,
      dexamethasone or their combination. Hepatic carboxyl esterase was depressed by
      dexamethasone (5 mg/kg) and was increased by the combination. Lipid peroxidation
      was not changed by dexamethasone (5 mg/kg) but was decreased by acetysal and the
      combination.

PMID- 8983932
TI  - A comparative bioavailability study to estimate the influence of an antacid on
      droxicam pharmacokinetics.
AB  - The influence of an antacid on droxicam pharmacokinetics was investigated in 12
      healthy male volunteers. A two way cross-over study was performed after the oral
      administration of 20 mg of droxicam (Ombolan capsules) and droxicam together with
      an antacid (Mucal powder). The plasma concentrations of piroxicam, the active
      moiety of droxicam, were determined by a high-performance liquid chromatographic
      method. The pharmacokinetic parameter values (mean +/- RSD) of piroxicam after
      administration of droxicam alone were: AUC0-->infinity = 125.5 +/- 25.1
      micrograms.h/l, Cmax = 2.08 +/- 19.9 micrograms/l, tmax = 7.08 +/- 36.8 h and
      t1/2 = 46.3 +/- 27.0 h. Following administration of droxicam together with the
      antacid the values obtained for the same parameters were: AUC0-->infinity = 135.1
      +/- 24.1 micrograms.h/l. Cmax = 1.85 +/- 23.9 micrograms/l, tmax = 8.17 +/- 34.9
      h and t1/2 = 52.0 +/- 22.4 h. These results indicate that concurrent
      administration of the antacid does not significantly change the bioavailability
      and pharmacokinetics of droxicam.

PMID- 8983934
TI  - Effect of polysaccharide peptide (PSP) on in vivo sulphation and glucuronidation
      of paracetamol in the rat.
AB  - The effect of polysaccharide peptide (PSP), an immunomodulator isolated from
      Coriolus versicolor COV-1, on the disposition of paracetamol was investigated in
      the rat. PSP (100 and 200 mg/kg, i.v.) was administered 30 min before a moderate
      dose (100 mg/kg, i.v.) of paracetamol was given. Plasma and bile concentrations
      of paracetamol, paracetamol glucuronide and paracetamol sulphate were measured by
      high performance liquid chromatography. The pharmacokinetics of paracetamol (100
      mg/kg) alone was consistent with those reported previously, using a one
      compartment model. PSP (200 mg/kg) significantly (P < 0.05) increased the
      clearance (controls, 19.06 +/- 2.74 ml/min/kg: PSP treated, 26.22 +/- 0.84
      ml/min/kg) and volume of distribution (controls, 1.35 +/- 0.11 l/kg: PSP treated,
      1.61 +/- 0.04 l/kg) of paracetamol by 37% and 21%, respectively. These changes
      were associated with concomitant increases in the glucuronide and sulphate
      metabolites in plasma, with significant increases in the Cmax and Tmax for both
      metabolites. The biliary excretion rate of paracetamol glucuronide and
      paracetamol sulphate were also measured. The Cmax values of paracetamol sulphate
      were significantly (P < 0.01) increased by 2.4-fold from 907.8 +/- 157.7
      micrograms/ml (controls) to 3061 +/- 331 micrograms/ml after PSP treatment. The
      lower dose of PSP (100 mg/kg) had no significant effect on the disposition of
      paracetamol in this study, which agreed with previous reports that a low dose of
      PSP (100-200 mg/kg, i.p.) was less effective in the protection against
      paracetamol-induced hepatotoxicity. The time course of the increase in
      paracetamol sulphate in plasma and bile in this study coincided with the
      transient perturbation of glutathione (GSH) turnover by a similar dose range of
      PSP previously described, such that more cysteine was available for oxidation to
      inorganic sulphate. This increase in sulphate conjugation by PSP would, in part,
      contribute to the increase in disposition of paracetamol and may be related to
      the ability of PSP to decrease the covalent binding of paracetamol to microsomal
      proteins previously reported. Further studies are necessary to understand the
      mechanism(s) involved in the PSP-induced increases in paracetamol glucuronide and
      paracetamol sulphate formation and biliary excretion.

PMID- 8983935
TI  - Pharmacokinetics of tolfenamic acid in pediatric patients after single oral dose.
AB  - The pharmacokinetics of tolfenamic acid, a non-steroidal anti-inflammatory drug,
      were determined following administration of a 1 mg/kg single oral dose of
      tolfenamic acid suspension to 6 feverish children. Their ages were from 2-14
      years (mean 7.5 years) and their weights were from 12-50 kg (mean 29.2 kg).
      Tolfenamic acid produced a significant fall in temperature (about 2 degrees C)
      compared to the initial value before oral intake of the drug and was well
      tolerated without adverse effects. Blood samples for determination of tolfenamic
      acid concentrations in plasma were obtained at timed intervals for up to 8 h post
      dose. Plasma concentrations of tolfenamic acid were determined using a reversed
      phase HPLC method and pertinent pharmacokinetic parameters were estimated by
      model-independent standard methods and were the following: the mean peak plasma
      concentration (Cmax +/- SEM) was 1.09 +/- 0.44 micrograms/ml (range, 0.65-1.63
      micrograms/ml) and the mean time (tmax +/- SEM) to reach peak plasma
      concentration was 1.4 +/- 0.4 h (range, 0.5-3.0 h). The mean area under the
      plasma concentration-time curve (AUC0-->infinity +/- SEM) was 4.61 +/- 0.40
      micrograms.h/ml (range, 2.74-5.98 micrograms.h/ml), the mean elimination half
      life (t1/2 +/- SEM) was 2.82 +/- 0.21 h (range, 2.19-3.40 h) and the mean
      apparent total clearance (CL/F +/- SEM) was 3.83 +/- 0.41 ml/min/kg (range, 2.79
      6.08 ml/min/kg).

PMID- 8983936
TI  - Pharmacokinetics of carbamazepine derived from a new tablet formulation.
AB  - The pharmacokinetics of a new tablet formulation of carbamazepine, an
      antiepileptic agent, have been investigated in 9 normal healthy subjects. The
      drug was given as a single oral dose of 400 mg. Ten blood samples were collected
      after administration. Plasma carbamazepine concentrations were determined by a
      sensitive method (HPLC). Areas under the plasma level-time curves for each
      subject were evaluated by means of the trapezoidal rule. The peak plasma
      concentration of 3.96-8.25 mg/l was reached 4-24 h after drug administration. The
      terminal phase half-life was 22.19-39.61 h and a systemic clearance was 1.05-2.06
      l/h. The new tablet formulation of carbamazepine seems to be bioequivalent when
      compared to the one used so far. For the prediction of systemic availability and
      estimation of the first-pass metabolism, from plasma level data, a hepatic blood
      flow rate limited model were used. The systemic availability was 97.8-98.9% and
      the elimination of the drug on its first-pass through the liver was 1.13-2.20%.

PMID- 8983937
TI  - Comparative pharmacokinetics and bioavailability of two oral formulations of
      thiocolchicoside, a GABA-mimetic muscle relaxant drug, in normal volunteers.
AB  - The comparative pharmacokinetic and bioavailability profile of two different
      formulations (tablets and capsules) of thiocolchicoside was investigated in 8
      healthy male volunteers after administration of single oral 8 mg doses. Plasma
      samples were assayed by a capillary gas chromatography--mass spectrometry (GC-MS)
      method following enzymatic hydrolysis of thiocolchicoside to its aglycone (3
      demethylthiocolchicine) and no attempt was made to account for the possible
      occurrence of hydrolysis in vivo. Irrespective of the formulation used, the drug
      was rapidly absorbed from the gastrointestinal tract, peak levels of about 17
      ng/ml being detected within 1 h in most subjects. Elimination was rapid, with
      mean MRT values of 5-6 h. All kinetic parameters showed considerable
      interindividual variability but none differed significantly between the two
      formulations. Relative to the tablet formulation, the oral bioavailability of the
      capsule formulation was 1.06 +/- 0.39.

PMID- 8983938
TI  - In vivo stability and excretion of gadodiamide (GdDTPA-BMA), a hydrophilic
      gadolinium complex used as a contrast enhancing agent for magnetic resonance
      imaging.
AB  - The stability and excretion of [14C]-gadodiamide (GdDTPA-BMA) was studied in male
      rats after i.v. injection of 0.3 mmol/kg [14C]-GdDTPA-BMA (Gd
      diethylenetriaminepentaacetic-acid-bis-methylamide) formulated as gadodiamide
      injection (OMNISCAN, Nycomed Imaging AS, Oslo, Norway). Samples of blood and
      urine obtained within 60 min and 6 h postdosing, respectively, were analyzed for
      radiolabeled compounds. Analysis of GdDTPA-BMA in high and low molecular weight
      fractions of serum indicated no protein binding. HPLC analyses of urine samples
      obtained 0-2 h, 2-4 h and 4-6 h after injection revealed no detectable amounts of
      biotransformation products of GdDTPA-BMA. Serum samples obtained 30 min and 60
      min after injection contained 9-13 microM of an unidentified compound which had a
      retention time different from all conceivable metabolites of gadodiamide. A
      similar concentration of this unknown compound was found in spiked predose serum
      samples. The total amount of the unknown compound in serum was less than 1% of
      the injected dose of [14C]-gadodiamide injection. It is concluded that
      gadodiamide, when administered i.v. as gadodiamide injection at a dosage of 0.3
      mmol/kg, is stable in vivo and that the very major part of the dose (> 99%) is
      excreted in urine as an unchanged complex.

PMID- 8983939
TI  - Bioequivalence study of two pharmaceutical forms of rifampicin capsules in man.
AB  - In this study the bioavailability of a new pharmaceutical form of rifampicin,
      Rifampicine Generic (300 mg capsules), was compared to a reference form Rimactan
      (300 mg capsules). Twelve healthy volunteers participated in a cross-over study.
      Each dosage form was administered, one after the other, to each subject in the
      morning after a fasted night period. Both forms were well tolerated and no side
      effects were observed in any of the subjects during the study. Blood samples were
      collected over 10 h. The rifampicin plasma concentrations were determined by an
      HPLC method. The pharmacokinetic parameters, Cmax, Tmax, AUC0-10h (mean +/- SD),
      were 6.06 +/- 2.95 micrograms/ml, 2.33 +/- 1.60 h, 25.57 +/- 12.6 micrograms.h.ml
      1, respectively, for the new form and 6.55 +/- 2.47 micrograms/ml, 2.04 +/- 1.37
      h, 26.11 +/- 9.10 micrograms.h.ml-1, respectively, for the reference form. The
      statistical analysis of different parameters with the Westlake method, ANOVA, and
      the Wilcoxon test with a probability of 95% showed no differences between the two
      forms of rifampicin. It was concluded that Rifampicine Generic 300 mg capsules
      are bioequivalent to Rimactan 300 mg capsules.

PMID- 8983940
TI  - A splice variant of arrestin from human retina.
AB  - Retinal arrestin is known to participate in the quenching of phototransduction
      through binding to light-activated and phosphorylated rhodopsin. Recently, a
      splice variant of retinal arrestin was identified in bovine photoreceptors which
      could bind unphosphorylated photoactive rhodopsin. In this report, a splice
      variant of retinal arrestin is identified in the human retina. The variant of
      human arrestin is produced by splicing out exon 12, unlike the bovine variant
      which is produced by splicing out exon 16. This 78 bp deletion in the human
      splice variant produces a polypeptide with a calculated molecular weight of 42.2
      kDa that lacks 26 amino acids when compared to the full-length retinal arrestin.
      The use of quantitative competitive PCR indicates that the mRNA for the human
      splice variant of arrestin is present at approximately one-twentieth of the level
      of human arrestin mRNA.

PMID- 8983942
TI  - Morphological changes in rabbit ciliary epithelium and blood-aqueous barriers
      after intravitreal 10(-5) M endothelin-1.
AB  - Morphological changes in the ciliary epithelium and blood-aqueous barriers were
      observed with a tracer, horseradish peroxidase, after 10 microliters of 10(-5) M
      endothelin-1 was injected intravitreally. A decrease of intraocular pressure and
      an increase of anterior chamber flare were found, and the structure of the
      ciliary epithelium changed drastically 6-7 hr after the injection. Swelling of
      mitochondria appeared in both non-pigmented and pigmented epithelial cells of the
      ciliary body. Intercellular spaces and ciliary channels were markedly dilated in
      the iridial processes. Some non-pigmented epithelial cells in both iridial and
      ciliary processes appeared to be degenerated and necrotic. Horseradish peroxidase
      leaked into the posterior chamber via extremely dilated ciliary channels and
      necrotic cells. The dose of 10(-5) M endothelin-1 seems to be so large that a
      toxic action occurred. The mechanism of the effect of endothelin on intraocular
      pressure was also discussed.

PMID- 8983941
TI  - Characterization of three isoforms of a 9 kDa gamma D-crystallin fragment
      isolated from human lenses.
AB  - The purpose of this study was to determine whether a 9 kDa gamma D-crystallin
      fragment, on in vivo post-translational modifications, exists as isoforms in the
      water soluble protein fraction of human lenses. In this study, three isoforms of
      the 9 kDa polypeptide (named as 9 kDa I, II and III) were identified and
      purified. In addition, the possible modified amino acids and their locations in
      the three isoforms were identified. The purification of the three isoforms was
      achieved by four steps which included separation of a mixture of crystallin
      fragments from the intact crystallins by a Sephadex G-50 chromatography under
      denaturing conditions, followed by purification of the 9 kDa polypeptide isoforms
      by a non-denaturing gel electrophoresis, preparative SDS-PAGE and HPLC using a C
      18 column. Each of the isoforms showed a single protein band and a single peak
      during SDS-PAGE and HPLC analyses respectively. The three isoforms on their
      partial N-terminal sequence analyses, exhibited sequence identical to gamma D
      crystallin starting at residue no. 87 suggesting that the isoforms contained
      residues no. 87 to 173 of gamma D-crystallin. On comparison of the amino acid
      compositions of the isoforms with that of the identical 9 kDa gamma D-crystallin
      fragment, the isoforms showed relatively lower amino contents of Asp, Arg, Leu
      and Tyr residues suggesting modifications of these residues in the isoforms. To
      identify the specific regions at which these amino acid residues were modified,
      the Western blot analysis with six site-specific polyclonal antibodies to six
      regions of the 9 kDa gamma D-crystallin polypeptide was carried out. Of the six
      antibodies raised, one was to the N-terminal region (residue nos 87-95; named as
      anti-9 kDa N-Ab), second to the C-terminal region (residue nos 165-173; named as
      anti-9 kDa C-Ab) and four to the four different middle regions [named as anti-9
      kDa M1 (nos 94-100)-Ab, M2 (nos 114-120)-Ab, M3 (nos 137-143)-Ab and M4 (nos 149
      154)-Ab] of the polypeptide. The Western blot analysis suggested that the 9 kDa I
      and 9 kDa II isoforms had modified amino acid residues in the regions of residue
      nos 114-120 and 165-173 whereas the 9 kDa III isoform in the regions of residue
      nos 114-120, 137-143, 149-154 and 165-173. It was also determined whether the 9
      kDa isoforms exhibit an age-related appearance in human lenses. Western blot
      analysis as above of the WS-proteins from lenses from donors of different ages
      was carried out. On comparison of these results with an identical Western blot
      analysis of the three purified 9 kDa isoforms, I, II and III, it was inferred
      that the 9 kDa isoform III appeared earlier than other isoforms during aging in
      human lenses.

PMID- 8983943
TI  - The effect of concentration on the structure of alpha-crystallin.
AB  - Several models have been proposed for arrangement of the subunits in alpha
      crystallin. These include the contrasting proposals that subunits are arranged in
      three layers and that subunits assemble into micelle-like structures. The
      validity of the micelle model was investigated by examining the effects of
      variations in protein concentration on the surface tension, conductivity,
      molecular weight and conformation of alpha-crystallin. The data were compared
      with those obtained for bovine serum albumin (BSA) and sodium dodecyl sulphate
      (SDS). Measurements of surface tension were conducted in the range, 10 micrograms
      ml-1 to 130 mg ml-1, in low and high ionic strength buffers. An apparent point of
      inflection, independent of ionic strength, was seen in alpha-crystallin's surface
      tension at around 1.9 mg ml-1 (95 microM). The surface tension did not plateau
      beyond this point, as is the case with surfactants, but continued to decrease up
      to 130 mg ml-1. BSA exhibited similar surface tension properties with an apparent
      inflection at 0.9 mg ml-1 (13 microM). The conductivity of alpha-crystallin and
      BSA solutions increased smoothly with no sign of any transition up to 96 mg ml-1
      and 60 mg ml-1, respectively. In contrast, SDS showed a clear transition in this
      property at the concentration corresponding to its CMC. The aggregation state of
      the alpha-crystallin aggregates was examined by comparing molecular masses and
      Stokes radii. The size of the protein remained uniform over a wide concentration
      range and was unaffected by variations in ionic strength. Protein conformation,
      which was monitored by examining the microenvironment of tryptophan residues, was
      also found to be independent of protein concentration. It is concluded that over
      the concentration range that was investigated, alpha-crystallin does not exhibit
      any of the properties associated with classical micelles formed from small
      amphiphilic molecules.

PMID- 8983944
TI  - Interaction between head-down tilt and anterior chamber infusions on intraocular
      pressure of anesthetized rats.
AB  - Head-down tilt or infusions of a balanced salt solution into the anterior chamber
      of the eye raise intraocular pressure. We measured intraocular pressure directly
      in adult male Sprague-Dawley rats, anesthetized with pentobarbital, and subjected
      to 45 degrees head-down tilt alone, tilt with an anterior chamber infusion (0.087
      microliter min-1), or tilt with an infusion containing arginine vasopressin. The
      intraocular pressure of the three groups differed during the 1 hr tilt and
      recovery periods. In the case of tilt alone, intraocular pressure quickly reached
      a peak after tilting, partially decreased during the tilt period, recovered to
      baseline immediately after tilt, then a secondary rise occurred. Combined
      infusion and tilt caused a slower rise to peak intraocular pressure, and only a
      partial recovery occurred during the 1 hr recovery period. Combined vasopressin
      infusion and tilt caused a gradual rise in intraocular pressure of a lesser
      magnitude than the other groups, followed by a rapid recovery to baseline
      pressure and no secondary rise. Systemic arterial pressure was stable within and
      between the groups. The underlying mechanism for these differing response
      patterns is unknown. However, some evidence indicates that infusions are
      independent of aqueous synthesis rate, and that vasopressin, acting on a V1
      receptor subtype reached from the anterior chamber, exerts a vascular effect.

PMID- 8983945
TI  - Regulatory volume increase of human non-pigmented ciliary epithelial cells.
AB  - Cells (ODM/SV40) derived from human non-pigmented ciliary epithelial cells were
      studied by electronic cell sizing. After transiently suspending the cells in
      hypotonic solution, isotonicity was restored by addition of sucrose. The cell
      volumes (vc) initially fell below those of control isotonic suspensions, and
      subsequently increased towards the baseline level. This secondary increase in vc
      is termed the regulatory volume increase (RVI). Results obtained with ionic
      substitutions and transport inhibitors indicate that four ionic mechanisms can
      support the RVI in these cells: coupled Na+/H+ and Cl-/HCO3- antiports, a Na+/Cl-
      symport, a Na+/K+/2Cl- symport, and a Na+ channel in parallel with a Cl-/HCO3-
      antiport. Arachidonic acid metabolites regulate the RVI very differently from
      their effects on the regulatory volume response (RVD) of the same cells to cell
      swelling. Prostaglandin E2 (PGE2), leukotriene (LTD4) and the PKC-inhibitor
      staurosporine all inhibit the RVI. Blockade of the cyclooxygenase, lipoxygenase
      and epoxygenase pathways of arachidonic acid metabolism [with 5,8,11,14
      eicosatetraynoic acid (ETYA)] produces a net acceleration of the RVI. In
      contrast, PGE2 and staurosporine stimulate, LTD4 has no effect, and ETYA inhibits
      the RVD. We suggest that knowledge of the ionic mechanisms and intracellular
      signalling underlying the RVI phenomenon may provide a basis for reducing the
      rate of net aqueous humor formation by increasing the rate of reabsorption of
      fluid from the aqueous humor into the non-pigmented ciliary epithelial cells.

PMID- 8983946
TI  - Bacterial proteases and adherence of Pseudomonas aeruginosa to mouse cornea.
AB  - The goal of this study was to test whether bacterial exoproducts, such as
      elastase or alkaline protease contribute to the initial binding of Pseudomonas
      aeruginosa to mouse corneal epithelium. Each protease, purified from P.
      aeruginosa, when applied exogenously at concentrations of either 25 or 50 ng ml
      1, elevated binding of Pseudomonas to mouse cornea in organ culture. Polyclonal
      antibodies against bacterial alkaline protease, but not elastase, interfered with
      bacterial binding and reduced significantly the number of organisms bound to
      cornea in an organ culture binding inhibition assay. Zymographic analysis of
      conditioned media from additional organ culture experiments showed that the P.
      aeruginosa strain used, which is highly virulent in cornea in vivo, secretes
      detectable levels of alkaline protease, but not elastase in vitro and that
      secretion was enhanced if the corneal epithelium was wounded. Lastly, how
      alkaline protease enhanced bacterial binding to the corneal epithelium of the
      organ cultured eye was examined. Data from this study suggest that exposure of
      lipase-sensitivity epithelial receptors represents at least one mechanism.

PMID- 8983947
TI  - Spatial mapping of polarized light transmission in the central rabbit cornea.
AB  - In this paper polarized light transmission measurements are made under conditions
      that closely approximate the physiological state in order to probe lamellar
      structure in the central cornea of New Zealand white rabbits. The results are
      interpreted with the aid of a newly developed theory (published elsewhere) in
      which the cornea is modeled as stacked birefringent layers corresponding to the
      lamellae. The theory enables predictions of the statistical properties of
      lamellar ordering based on characteristics of the transmission of polarized
      light. The experimental results are consistent with a structure in which a number
      of lamellae have a fixed azimuthal orientation (i.e. about an axis normal to the
      corneal surface), whereas the remainder are essentially randomly oriented.
      Comparisons with the theoretical predictions are consistent with a model in which
      the preferred direction in the apical region of the cornea does not vary
      significantly among rabbits; and the preferred lamellar orientation direction
      determined for the population measured here is very close to that suggested in
      previous experiments on a smaller number of rabbits. Mapping experiments using a
      new goniometric holder showed that the preferential order at the apical region is
      closely preserved throughout the central approximately 4 mm diameter optical zone
      in individual corneas.

PMID- 8983948
TI  - The effect of chronically elevated intraocular pressure on the rat optic nerve
      head extracellular matrix.
AB  - The extracellular matrix of the optic nerve head is altered in both human
      glaucoma and in experimental primate models of this disease. However, the
      relationship of this change to glaucomatous optic nerve degeneration is unknown.
      This report describes similar matrix alterations in rats with unilateral elevated
      intraocular pressure. Brown Norway rats received episcleral vein injections of
      hypertonic saline to produce prolonged elevations of intraocular pressure. After
      up to 6 months of pressure elevation, optic nerve head sections from the rats
      were evaluated by light microscopic immunohistochemistry using antibodies to
      collagens I, III, IV and VI, laminin, elastin and chondroitin and dermatan
      sulfate proteoglycans. In experimental eyes with 11 days or more of pressure
      elevation, depositions of collagen IV, collagen VI and laminin were found within
      regions of the optic nerve head that, in normal eyes, are occupied solely by
      nerve bundles. Collagen I and III deposition appeared to be more dependent on the
      level and duration of the pressure rise. Eyes with lower mean intraocular
      pressures showed deposits of interstitial collagens primarily at the level of the
      sclera, while eyes with higher mean pressure elevations had depositions in the
      neck regions as well. Chondroitin and dermatan sulfate proteoglycans were
      deposited in a pattern similar to that of collagen I. No extracellular matrix
      deposition was seen in the orbital optic nerve in any experimental eye. These
      extracellular matrix changes in rats replicate previous findings in human
      glaucomatous eyes and monkey eyes with experimentally elevated pressures. They
      also suggest a sequence of extracellular matrix protein deposition in response to
      pressure elevation. The optic nerve head deposition of matrix materials in
      response to elevated intraocular pressures may affect the susceptibility of
      remaining axons to pressure by changing the physical properties of their support
      tissues, by affecting the support functions of astrocytes and by changing the
      microenvironment of injured axons. This model may be useful for studying these
      and other aspects of the process of axonal injury resulting from elevated
      intraocular pressure.

PMID- 8983949
TI  - Dexamethasone inhibits trabecular cell retraction.
AB  - Glucocorticosteroids such as dexamethasone (Dex) are known to cause an increased
      resistance to aqueous outflow in the intact and cultured eye. We investigated
      whether Dex treatment of cultured endothelial or trabecular meshwork (TM) cells
      might interfere with the cell separations and retraction induced by the facility
      enhancing agents ethacrynic acid (ECA), cytochalasin B and the calcium chelator
      EGTA. Our hypothesis was that Dex-induced changes in the response of our model
      cells in vitro might serve as a paradigm for those produced in the cells of the
      outflow pathway, perhaps through influencing the changing dimensions of the
      pathway for aqueous humor through the juxtacanalicular tissue and/or inner wall
      of Schlemm's canal. We treated calf pulmonary artery endothelial (CPAE) and human
      and porcine TM cells with Dex (1-100 microns, 1-9 days), and then assessed
      monolayer and cytoskeletal integrity by immunofluorescence microscopy for tubulin
      and direct fluorescence staining for F-actin after exposure to the agents named
      above. We found that Dex-pretreated CPAE and TM cells gradually (over 5-7 days)
      became refractory to the effects of both ECA and EGTA, but not to cytochalasin B.
      Despite the preservation of general cell shape and attachment after ECA in Dex
      treated cells, microtubule disruption still took place as in controls. Dex
      treated cells also demonstrated a reorganization of filamentous actin staining
      after ECA and EGTA. Combination experiments of ECA and EGTA in Dex-treated cells
      suggested that the Dex effects were due to a greater strength of cell-to-cell and
      cell-to-substrate attachment, possibly due to interference with the normal
      cellular signaling required for coordinated cellular retraction and junctional
      disruption.

PMID- 8983950
TI  - Transferrin-ricin A chain toxin limits the development of experimental
      proliferative vitreoretinopathy.
AB  - This study was designed to determine the safety and efficacy of transferrin-ricin
      A chain toxin (Tfr-rRA) at preventing retinal detachment in a rabbit model of
      proliferative vitreoretinopathy (PVR). The toxicity of intravitreal Tfr-rRA (1000
      5000 ng) was determined by indirect ophthalmoscopy and electroretinography on
      days 1, 5, 8, 16, 26 and 48 post-injection, and by light and transmission
      electron microscopy conducted on eyes enucleated 48 days after drug exposure. PVR
      was created by injecting 25,000 homologous fibroblasts into the vitreous cavity
      of eyes which had previously undergone a gas compression vitrectomy. Eyes then
      received intravitreal Tfr-rRA (2000 ng) or vehicle. Animals were examined on days
      1, 4, 7, 10, 14, 21 and 28 post-injection. Intravitreal injection of 1000 and
      2000 ng Tfr-rRA did not show ophthalmoscopic or electroretinographic toxicity.
      Injection of 5000 ng Tfr-rRA showed mild retinal whitening, retinal arteriolar
      narrowing, and electroretinographic toxicity, but no morphologic damage, such as
      photoreceptor loss, nuclear layer vacuolation, or inflammatory cell infiltration,
      to the retina. Tfr-rRA (2000 ng) injected intravitreally 3 days after fibroblast
      injection prevented traction retinal detachment in 90% of eyes compared to 22% of
      sham treated eyes (P < 0.001). The data from this study suggest that transferrin
      ricin A chain toxin (2000 ng) safely and effectively limits retinal detachment in
      experimental PVR.

PMID- 8983951
TI  - The effects of prenatal exposure to cocaine on the dopaminergic cells in the rat
      retina. An immunocytochemical and neurochemical study.
AB  - There is a growing consensus that the development of the eye is affected by
      prenatal exposure to cocaine. Considering that the retina is affected by prenatal
      cocaine exposure, that this drug affects the dopaminergic systems, that the
      dopaminergic cells in the retina show a well-defined pattern of development and
      that they can be specifically stained in wholemounts by the antibody anti
      tyrosine hydroxylase (TH), this study was undertaken to evaluate the effects of
      in utero cocaine exposure on the dopaminergic cells of the rat retina. Pregnant
      Wistar rats were given 60 mg (kg body weight)-1 day-1 of cocaine hydrochloride,
      subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats
      were pair-fed. At PND14, 30 and 90, male offspring from different litters were
      perfused with fixative and the retinas processed as wholemounts and immunostained
      with the antibody anti-TH. Rats from other groups were decapitated at the same
      post-natal ages, the retinas dissected and processed by neurochemical techniques
      to measure the concentrations of dopamine, its metabolites and the turnover of
      dopamine. There was a significant increase of the retina surface area between
      PND14-30 in the control group, which was not found in the cocaine group. The
      density of the immunostained small TH cells was lower in the cocaine groups. No
      drug-effects were detected in the density of the large TH cells. The densities of
      the total large and small cells in the superior, inferior and nasal hemiretinas
      were similar to those found in the whole retinas; however, in the temporal
      hemiretinas of the cocaine groups, the density of the large TH cells was higher
      and of the small TH cells was lower than in controls, resulting in an absence of
      effects on the total density of TH-cells in this hemiretina. A transient increase
      in the level of dopamine metabolite (DOPAC) and of the turnover of dopamine at
      PND14 was detected in the cocaine groups. All quantitative parameters reached
      normal values, in all groups, at PND90. These results show that, during the
      critical periods in which catecholamines can influence the development of
      neurons, cocaine transiently affects the pattern of dopaminergic neurons in the
      retina. This may have functional importance due to the role of this
      neurotransmitter as a regulatory and/or trophic factor in developing neuronal
      circuitries.

PMID- 8983952
TI  - Expression of thrombospondin 1 by adult lens epithelium.

PMID- 8983953
TI  - Sequence and expression of chicken betaA2- and betaB3 crystallins.

PMID- 8983954
TI  - Moderation of herpetic stromal keratitis by basic fibroblast growth factor.
AB  - The effect of basic fibroblast growth factor (bFGF) on the evolution of herpes
      simplex virus (HSV) infection in eyes of rabbits was investigated. Rabbit eyes
      were infected with HSV-1 by a non-invasive inoculation and treated for 7 days
      with an eye drop solution containing either bovine bFGF (50 ng; three times
      daily), or bFGF diluent as control. The treatment started 2 hr, 24 hr or 96 hr
      post-inoculation (p.i.). Follow-up of clinical disease parameters, such as
      conjunctivitis, epithelial keratitis, stromal disease, corneal neovascularization
      and of viral isolation continued for 17 days. The most significant difference
      between bFGF and control treatments was observed in the development of stromal
      keratitis. The incidence of stromal disease in the bFGF treated group (2/16 eyes)
      was significantly lower than in the control group (11/12 eyes) (P = 0.0001), when
      bFGF was administered 2 hr or 24 hr p.i. The severity of the disease developed in
      the bFGF treated eyes was also milder than in the control eyes (determined by
      serial slit-lamp clinical examinations and by histologic sections). Such effect
      was not demonstrated if the treatment started 96 hr p.i. The same duration of
      viral shedding was obtained with bFGF treated eyes (2 hr, 24 hr, or 96 hr p.i.)
      and control eyes. Neither HSV-1-infected, nor sham-inoculated bFGF-treated eyes
      demonstrated increased neovascularization of the cornea, as compared with the
      corresponding vehicle-treated control eyes. This study demonstrates that bFGF
      treatment (starting 2-24 hr p.i.) decreased the occurrence and severity of
      herpetic stromal keratitis, without subsequent aggravation of corneal
      vascularization. This beneficial anti-inflammatory effect of bFGF may have future
      application in the treatment of the most devastating stage of herpetic corneal
      infection.

PMID- 8983955
TI  - Hypoxic and excitotoxic damage to cultured rat retinal ganglion cells.
AB  - The cytotoxic effects of hypoxia and excitatory amino acids on cultured retinal
      ganglion cells were studied. The influence of coculture with retinal Muller glia
      and cortical astrocytes on cell survival was evaluated, as were the effects of
      the N-methyl-DL-aspartate inhibitor, MK-801. Dissociated retinal neurons from 7
      day-old Sprague-Dawley rats were plated on a laminin substrate, neocortex-derived
      glial monolayers, or Muller cell monolayers. Ganglion cells were labeled by
      injection of DiI into the superior colliculus 2 days prior to dissociation.
      Exposure of cultured ganglion cells to glutamate and N-methyl-DL-aspartate showed
      a time- and concentration-dependent survival rate. Exposure of cells to hypoxia
      demonstrated a survival rate that was dependent on time and O2 concentration.
      Excitotoxic and hypoxic damage was entirely blocked by the specific non
      competitive inhibitor of N-methyl-DL-aspartate, MK-801. Retinal ganglion cells
      cultured on cortical astrocytes and retina-derived Muller glia showed
      significantly better survival rates (P < 0.001) than cells cultured on laminin
      coated dishes under control conditions, in hypoxia (9% to 15% O2), and after
      exposure to 200 microM glutamate. Retinal ganglion cells cultured on Muller glia
      showed significantly better survival rates (P < 0.01) than those cultured on
      cortical astrocytes under conditions of hypoxia (9% to 15% O2) and exposure to
      200 microM glutamate. The results demonstrate that excitotoxic and hypoxic damage
      to cultured retinal ganglion cells is moderated by NMDA receptor blockade and by
      the presence of glial cells, especially retinal Muller cells. This system may
      provide a useful model for studying the pathophysiology of excitotoxicity and
      hypoxia on cultured retinal ganglion cells, and may be used to help identify
      potentially clinically useful therapeutic agents.

PMID- 8983956
TI  - Immunological localization of GABAA-receptor subunits in cultured human and rat
      retinal pigment epithelium.

PMID- 8983957
TI  - Corneal aldehyde dehydrogenase displays antioxidant properties.

PMID- 8983958
TI  - RNA and protein synthesis in the primate lens.

PMID- 8983959
TI  - Identification of possible regions of chaperone activity in lens alpha
      crystallin.

PMID- 8983961
TI  - Vasoactive intestinal peptide-stimulated glycoconjugate secretion from
      conjunctival goblet cells.
AB  - We have developed an in vitro and in vivo method to determine if VIP-stimulates
      conjunctival goblet cell secretion in the rat as nerves which contain vasoactive
      intestinal peptide (VIP) and are most likely parasympathetic are localized around
      these cells. For the in vitro method, pieces of rat conjunctiva were incubated
      for 1 hr with no additions or increasing concentrations of VIP (10(-10)-10(-6)M).
      Goblet cell secretion was measured by determining the amount of Helix pomatia
      agglutinin (HPA)-detectable glycoconjugates secreted into the medium. HPA
      detectable glycoconjugates were assayed using an enzyme-linked lectin assay. For
      the in vivo method, drops of buffer containing no additions or varying
      concentrations of VIP (10(-10)-10(-6) M) were placed on the ocular surface of
      anesthetized rats for 60 min. The rats were killed, the ocular surface chemically
      fixed, and a button of conjunctiva removed. Mucin-containing goblet cells were
      stained by Alcian blue-periodic acid Schiff's reagent and the number of cells per
      0.16 mm2 was quantified. A decrease in the number of mucin-containing goblet
      cells indicated an increase in mucous secretion. By immunofluorescent
      histochemistry, we found that the lectin HPA was localized predominantly in the
      secretory granules of rat conjunctival goblet cells with little binding present
      in the remainder of the conjunctiva. Nerves containing VIP surrounded goblet
      cells labelled with HPA. In pieces of conjuctiva, in vitro VIP (10(-8)-10(-6) M)
      stimulated HPA-detectable glycoconjugate secretion in a concentration dependent
      manner. When applied topically to the ocular surface, in vivo VIP AT 10(-8) M
      stimulated mucous secretion from conjunctival goblet cells. We conclude that VIP
      is present in nerves around conjunctival goblet cells and stimulates
      glycoconjugate secretion from these cells.

PMID- 8983960
TI  - Expression and cellular localization of the kallikrein-kinin system in human
      ocular tissues.
AB  - Tissue kallikrein is a serine proteinase which processes kininogens to release
      bioactive kinins. Kinins mediate a variety of biological processes through the
      interaction with kinin receptors. Kinins are involved in the regulation of blood
      pressure and local blood flow, vasodilation, smooth muscle contraction and
      relaxation, production of pain and inflammation, and stimulation of cell
      proliferation. The tissue kallikrein-kinin system has been implicated in a number
      of pathophysiological processes such as hypertension, allergy and diabetes
      mellitus. In the present study, we have identified the expression and
      localization of components of the kallikrein-kinin system in the human eye by
      reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot
      analyses, and in situ hybridization histochemistry. RT-PCR and Southern blot
      analyses have detected mRNAs of the key components of the system including tissue
      kallikrein, low molecular weight kininogen, and bradykinin B1 and B2 receptors at
      high levels in human retina, choroid and ciliary body, and relatively low levels
      in the optic nerve. In situ hybridization has identified cellular localization of
      these four mRNAs in ocular tissues. They are expressed in retinal neuronal cells
      including the outer nuclear layer, inner nuclear layer and ganglion cell layer.
      These mRNAs were also identified in endothelial cells of ocular blood vessels,
      ciliary muscle and lens epithelial cells. The sense riboprobes showed negative
      staining, which indicates the specificity of the antisense riboprobes. These
      results suggest that the tissue kallikrein-kinin system is produced endogenously
      in human ocular tissues. Similar expression patterns of kallikrein, kininogen and
      kinin receptors indicate that the kallikrein-kinin system may function in an
      autocrine or paracrine fashion in the eye.

PMID- 8983962
TI  - Morphological and physiological consequences of the selective elimination of rod
      photoreceptors in transgenic mice.
AB  - We have produced transgenic mice (rdta mice) that express the gene for an
      attenuated diphtheria toxin under the control of a portion of the rhodopsin
      promotor. Morphologically, expression of this transgene results in the
      elimination of the majority of cell bodies in the outer nuclear layer (ONL) of
      the retina. This cell loss is evident as early as postnatal day 7 (P7), which
      corresponds closely to the onset of expression of rhodopsin in the mouse retina
      that occurs about P5. Reverse transcription-PCR (RT-PCR) analysis of mRNA from
      the retinae of rdta mice shows that the level of rhodopsin mRNA is reduced by 50%
      as early as P14 and by P28, has declined to approximately 15% of that in the
      retinae of control mice. Electroretinographic recordings from the dark-adapted
      rdta mice at P17 reveal that their retinae do not generate any rod-mediated
      signals. The majority of the cell bodies that persist in the ONL of the rdta
      retinae have the morphological features of cone photoreceptors, although these
      cells never develop normal inner and outer segments. To confirm that the
      surviving cells are cones we crossed the rdta mice to a different line of
      transgenic mice that express the E. coli beta-galactosidase (lacZ positive)
      reporter gene in all cone photoreceptors. In retinae from mice that inherit both
      transgenes, nearly every cell that remains in the ONL expresses lacZ and, thus,
      is a cone. This finding also is consistent with RT-PCR analyses, which show that
      cone opsin mRNAs persist in the retinae of our rdta mice at ages when rhodopsin
      mRNA is significantly reduced. Electroretinograms can be obtained from the rdta
      mice under conditions that saturate the rod response and, thus, providing
      evidence that the cones that remain are functional, even though they lack inner
      and outer segments. Finally, we have examined the inner nuclear layer for changes
      that result from rod photorecptors ablation. We show that, while the elimination
      of the rod photoreceptors has little or no effect on the morphology of the post
      synaptic neurons, this deletion does alter their laminar position.

PMID- 8983963
TI  - Movement of carboxyfluorescein across retinal pigment epithelium-choroid.
AB  - The movement of carboxyfluorescein (CF) across the isolated retinal pigment
      epithelium (RPE)-choroid of the albino rabbit was studied using an Ussing chamber
      under short-circuit conditions with CF concentrations ranging from 15 to 300
      microM. The inward (from the choroid to vitreous side) permeability of the tissue
      to CF showed no significant change over the concentration range tested, averaging
      2.2 x 10(-6) cm sec-1. Neither ouabain (1.0 microM), low external sodium
      concentration nor probenecid (100 microM) had significant effect on the inward
      movement of CF. The outward (from the vitreous to the choroid side) permeability
      of the tissue to CF gradually decreased as the concentration increased (ANOVA, P
      < 0.01: Scheffe's test, P < 0.05), averaging 3.7 x 10(-6) cm sec-1 at 75 microM.
      Further, it was always significantly greater than the inward permeability at the
      corresponding concentration (unpaired t-test, P < 0.05-0.01). The outward
      movement of CF was significantly inhibited by 2,4-dinitrophenol (10 microM),
      ouabain (1.0 microM), probenecid (100 microM), iodipamide (5.0 mM), hippurate (30
      mM) or low external sodium concentration (25 mM). The net outward movement of CF
      became saturated as concentration was increased and a Lineweaver-Burk plot gave
      an apparent Km of 237 microM and Vmax of 1.8 nmol hr-1 cm-2. The results
      indicated that part of the outward movement of CF across the RPE-choroid depends
      on carrier mediated active transport, but to a much lesser extent than that of
      fluorescein. The inward movement of CF was thought to occur almost exclusively by
      passive diffusion through the paracellular spaces.

PMID- 8983964
TI  - Characterization of alpha 2-adrenoceptor subtypes in the porcine eye:
      identification of alpha 2A-adrenoceptors in the choroid, ciliary body and iris,
      and alpha 2A- and alpha 2C-adrenoceptors in the retina.
AB  - The subtypes of alpha 2-adrenoceptor were characterized in the choroid, ciliary
      body, iris and retina of the pig eye by using radioligand binding. [3H]-MK912
      labelled dense populations of alpha 2A-adrenoceptors in the choroid and ciliary
      body. In the retina, [3H]-MK912 labelled both alpha 2A- and alpha 2C
      adrenoceptors. In the iris, receptors of the alpha 2A-adrenoceptor type were
      detected by using either [3H]-MK912 or [3H]-RX821002 as radioligands.

PMID- 8983965
TI  - The generation of superoxide anion by the UVA irradiation of human lens proteins.
AB  - In this study we report the generation of superoxide anion and hydrogen peroxide
      by a water-insoluble protein fraction from aged human lenses in response to UVA
      light. Irradiation with 1.5 kJ cm-2 of UVA light ( > 338 nm) over a 1 hr period
      caused the formation of 20 +/- 0.1 microM superoxide radical and 37 +/- 0.5
      microM hydrogen peroxide. A linear photolysis of SH-groups (21 nmol ml-1, 26%).
      His (117 nmol ml-1, 26%) and Trp (72 nmol ml-1, 27%) residues was seen following
      60 min of irradiation. The addition of SOD, however, had no effect on the
      photolytic destruction of any of these amino acid residues. Incubation of the
      human WISS proteins and bovine alpha-crystallin in the presence of 43-49 microM
      of O2- generated in a xanthine oxidase/hypoxanthine system over a 1 hr period,
      caused no loss of histidine, little or no loss of tryptophan and loss of 7-9 nmol
      ml-1 of sulfhydryl groups with both proteins. This argues that O2- can only
      account for the destruction of at most 4-8 nmol SH-groups in human water
      insoluble proteins following 1 hr of UVA irradiation.

PMID- 8983966
TI  - Quantitative and morphological changes of the choroid vasculature in RCS rats and
      their congenic controls.
AB  - In Royal College of Surgeons (RCS) rats the outer retina degenerates owing to a
      phagocytic defect of the retinal pigmented epithelium (RPE). To analyse whether
      the choriocapillaris also undergoes degenerative changes, corrosion casts of
      choroidal vessels of ten RCS rats and 12 age-matched controls of different age
      groups were investigated by scanning electron microscopy. The pattern of the
      ciliary arteries was analysed qualitatively and the areas covered by capillaries
      in the different quadrants and regions of the choroid were evaluated
      quantitatively. In both RCS rats and their congenic controls the choroid was
      supplied by only three ciliary arteries. A separate artery supplying the upper
      quadrant in other rat strains was lacking. The quantitative evaluation revealed
      that in controls the capillary density decreased from the central to the
      peripheral regions. In addition there were slightly fewer capillaries in the
      upper temporal quadrant compared to other quadrants. In RCS rats older than 6
      months, all parts of the choroid displayed a decrease in the number of
      capillaries of about 10-15% compared to the controls. Most prominent loss of
      capillaries was found in the upper temporal quadrant. Electron-microscopical
      investigation of the upper temporal quadrant showed that loss of choriocapillaris
      was directly correlated with degeneration of the adjacent retinal pigmented
      epithelium (RPE).

PMID- 8983967
TI  - Electron microscopic study of optic nerves of macular mice.
AB  - The optic nerve of the macular mouse as a model of Menkes' disease was examined
      by electron microscopy. Since hemizygote macular mice die at 14 or 15 days of
      age, they were treated with 50 micrograms CuCl2 per 0.1 ml distilled water at 7
      days of age. The optic nerves of 1-month-old hemizygote macular mice treated with
      copper showed hypomyelination and unmyelinated axons, while 1-month-old
      heterozygote macular mice had focal demyelination of axons. The number of
      myelinated axons in treated hemizygotes and heterozygotes was statistically
      significantly lower than that in the control littermates. Oligodendrocytes form
      myelin sheaths. Since oligodendrocytes of the hemizygote macular mice may have
      lower activities of cuproenzymes, such as cytochrome oxidase and superoxide
      dismutase, hypomyelination is assumed to be caused by the dysfunction of
      oligodendrocyte.

PMID- 8983968
TI  - Muller and RPE cell response to photoreceptor cell degeneration in aging Fischer
      rats.
AB  - With increasing age, retinas of male Fischer rats gradually lose photoreceptor
      cells beginning at the ora serrata and extending to the central retina resulting
      in a pronounced peripheral retinopathy. In this study, we used immunocytochemical
      methods for glial fibrillary acidic protein (GFAP) and carbonic anhydrase II (CA
      II) to study the Muller cell response to age-related photoreceptor cell
      degeneration in the superior retina. Retinas of Fischer rats were also examined
      by electron microscopy to investigate retinal pigment epithelial (RPE) cell and
      Bruch's membrane structural changes with advancing age. Our study showed
      extensive photoreceptor cell loss in the region of the ora serrata beginning by
      16 months, while few photoreceptor cells were found at 23 months.
      Neovascularization also occurred in the area of the peripheral retinopathy at the
      level of the RPE cells as determined by electron microscopy, as well as a
      thickening of Bruch's membrane with initial signs of small breaks. Dense areas of
      GFAP-immunostaining of Muller cell processes were found in the superior
      peripheral retina of 16-30 month-old rats where photoreceptor cells were
      degenerating. After 21 months, Muller cell processes extended into the subretinal
      space. However, in the central retina, where the photoreceptor cell population
      was more stable, GFAP-immunolabelled Muller cells were not detected. Immunoblots
      of retinal homogenates confirmed elevated GFAP levels at 18-30 months when
      compared to homogenates from retinas of 6-month-old Fischer rats. During
      photoreceptor cell degeneration, Muller cell processes were also prominently
      immunostained for CA II, which were seen to occupy the subretinal space at 18-30
      months. Our results suggest that Muller cells respond to the age-related
      peripheral retinopathy in Fischer rats by increasing GFAP content and growth of
      their processes into the subretinal space to form a glial scar, but only in the
      area of severe photoreceptor cell loss. In addition, RPE and Bruch's membrane of
      aged retinas exhibit typical early age-related changes as also reported for aged
      human eyes.

PMID- 8983969
TI  - Interleukin-1 beta increases prostaglandin E2-stimulated adenosine 3',5'-cyclic
      monophosphate production in rabbit pigmented ciliary epithelium.
AB  - This study was designed to determine the effects of interleukin-1 on basal and
      prostaglandin E2-stimulated adenosine 3',5'-cyclic monophosphate production by
      primary and first passage cultures of non-transformed rabbit pigmented and non
      pigmented ciliary epithelial cells. Confluent cultures of rabbit pigmented and
      non-pigmented ciliary epithelial cells were incubated for varying periods of time
      in serum-free medium with or without interleukin-1 beta, tumor necrosis factor
      alpha, bacterial lipopolysaccharide, transforming growth factor-beta 2,
      cycloheximide, indomethacin and combinations of these agents. Cells were then
      preincubated for 10 min with serum-free medium plus the phosphodiesterase
      inhibitor, 3-isobutyl-1-methylxanthine (for basal adenosine 3',5'-cyclic
      monophosphate production) or serum-free medium containing several concentrations
      of prostaglandin E2 and 3-isobutyl-1-methylxanthine. In certain experiments
      isoproterenol, vasoactive intestinal peptide, or forskolin was substituted for
      prostaglandin E2. Adenosine 3',5'-cyclic monophosphate was then extracted into
      ice-cold absolute ethanol and measured by radioimmunoassay. Prostaglandin E2
      stimulated adenosine 3',5'-cyclic monophosphate production in pigmented and non
      pigmented ciliary epithelial cells in a dose-dependent manner. Incubation with
      interleukin-1 beta (150 U ml-1) increased prostaglandin E2-stimulated, but not
      basal adenosine 3',5'-cyclic monophosphate production in pigmented ciliary
      epithelial cells. This interleukin-1 beta-induced enhancement of prostaglandin E2
      stimulated adenosine 3',5'-cyclic monophosphate production, called the
      interleukin-1 effect, was not seen with non-pigmented ciliary epithelial cells.
      The interleukin-1 effect was dependent upon interleukin-1 beta concentration,
      time and de novo protein synthesis. The interleukin 1 effect could not be
      reproduced by replacing interleukin-1 beta with tumor necrosis factor-alpha or
      bacterial lipopolysaccharide and was specific for prostaglandin E2, since
      interleukin-1 beta did not enhance isoproterenol-, vasoactive intestinal peptide
      , or forskolin-induced adenosine 3',5'-cyclic monophosphate production. Chronic
      exposure to prostaglandin E2 (during the 3 hr incubation period), with or without
      interleukin-1 beta in the incubation medium, reduced subsequent prostaglandin E2
      stimulated adenosine 3',5'-cyclic monophosphate production. Inhibition of de novo
      prostaglandin synthesis with indomethacin increased the interleukin-1 effect. The
      interleukin-1 effect was inhibited by the immunosuppressive cytokine,
      transforming growth factor-beta 2, in a dose-dependent manner. This is the first
      report of prostaglandin E2-induced stimulation of adenosine 3',5'-cyclic
      monophosphate production by pigmented ciliary epithelial cells and of the unique
      ability of interleukin-1 to increase this effect. The results are consistent with
      interleukin-1-induced upregulation of prostaglandin E receptors. Since
      transforming growth factor-beta 2 inhibited this interleukin-1 effect, this
      immunosuppressive cytokine may exert negative feedback and thus regulate the
      physiological consequences of the interleukin-1 effect.

PMID- 8983970
TI  - Aqueous and vitreous penetration of ciprofloxacin following different modes of
      systemic administration.
AB  - The overall importance of the peak or the mean serum concentrations as predictors
      of ocular drug penetration is unknown. To address this fundamental question with
      an agent which shows promise as adjunctive therapy in the treatment of
      endophthalmitis, we studied the penetration of ciprofloxacin into the aqueous and
      vitreous humors following three different modes of systemic administration. New
      Zealand white rabbits received either a single bolus dose (40 mg kg-1), three
      intermittent doses of 13.33 mg kg-1 evenly spaced over an 8 hr period, or a
      continuous infusion of 40 mg kg-1 over an 8 hr period. Pharmacokinetic analysis
      was performed using RSTRIP II, a non-linear, least square regression model
      analysis program. The serum area under the concentration-time curve (AUC) values
      for each mode of drug administration were similar: 32.9 micrograms hr ml-1 for
      single dose, 31.9 micrograms hr ml-1 for intermittent dose, and 33.8 micrograms
      hr ml-1 for continuous infusion modes. The percentage penetration into the
      aqueous and vitreous were also similar; 30.5% and 6.5% for a single dose, 31.6%
      and 7.4% for intermittent doses and 30.0% and 7.5% for continuous infusion. The
      penetration into the aqueous and vitreous humors was not influenced by mode of
      administration. As with other quinolones we have studied, elimination rates were
      similar for the central and peripheral compartments in the post-distributive
      phase. Vitreous humor ciprofloxacin concentrations achieved were below that which
      inhibits most Staphylococcus epidermidis, the most common isolate in patients
      with post-operative endophthalmitis.

PMID- 8983972
TI  - Phagosome number and distribution in retinal pigment epithelial cells of vitiligo
      mutant mice.
AB  - The vitiligo mutant mouse has a disorder affecting the interaction of retinal
      pigment epithelium (RPE) and photoreceptor cells of the neural retina. Among the
      phenotypic features are patches of hyper- and hypopigmentation in the embryonic
      RPE, increased RPE cell production neonatally, and a later onset of progressive
      photoreceptor cell degeneration that continues for more than one year until all
      photoreceptor cells are gone. Failure of RPE microvilli to intertwine with rod
      outer segments (ROS) at any age, the accumulation of ROS membranous fragments in
      the subretinal space, and a relatively early retinal separation from the RPE
      suggested analysis of whether RPE phagocytosis might be impaired. Post-natal day
      23 (P23) and P36 mutant and congenic control wild-type mice were kept in darkness
      overnight and eyes were examined by light and transmission electron microscopy
      0.5 hr before, 1.5 hr after and 10.5 hr after lights turned on at 0700 hr. At
      these ages ROS have not yet degenerated, though they are shorter than normal and
      somewhat misoriented. The number of phagosomes per RPE cell was markedly reduced
      in mutants compared to controls at both ages and all time points. Nonetheless,
      the highest counts were obtained 1.5 hr after the lights turned on in mutant and
      control specimens. In the mutant eyes, the proportion of phagosomes in the
      microvillous zone of the RPE cells was consistently lower than in any other
      cellular compartment. Phagosome distribution in the apical and basal zones of the
      RPE cell cytoplasm was within normal limits. Macrophage-like cells become
      numerous in the subretinal space at older ages, but were already present at P23
      and P36, and contained phagosomes in their cytoplasm. The hypothesis is proposed
      that binding of ROS to RPE cells might be defective in vitiligo mice, in contrast
      to the rdy rat, where the work of others indicates that binding is normal and the
      subsequent ingestion of phagosomes is impaired.

PMID- 8983971
TI  - A novel system to measure labelled CO2 and HCO3- fluxes across epithelia: corneal
      epithelium as model tissue.
AB  - A method that allows for an accurate measurement of 14C-labelled fluxes of HCO3-
      and/or CO2 across epithelia is described. It is based on the principle that in a
      closed system the specific activities of HCO3- and CO2 are equal to each other.
      The hemichambers between which the tissue was mounted were modified Ussing-type
      chambers that included a capacity for recirculation and mixing of the labelled
      fluid and gas phases within a closed system. The isolated frog corneal epithelium
      was used as a model system. In solutions containing 25 mM HCO3- and 5% CO2, the
      unidirectional fluxes from tear to stroma (t-s) and stroma to tear (s-t) were
      3.08 +/- 0.12 and 2.33 +/- 0.11 mu eq h-1 cm-2 (means +/- S.E.S), respectively,
      with a statistically significant t-s net flux. These fluxes were independent of
      the presence of Cl- in the bathing solutions. The bilateral addition of
      methazolamide (10(-4) M) reduced both unidirectional fluxes to about 2.0 mu eq h
      1 cm-2. This finding was a strong indication of the presence of carbonic
      anhydrase (CA) in the corneal epithelium as well as its involvement in the
      production of the net flux of 14C-label. In nominally CO2-free media,
      unidirectional t-s and s-t fluxes were 0.19 +/- 0.03 and 0.27 +/- 0.05
      respectively. These fluxes were not affected by methazolamide. The s-t net HCO3-
      flux can result from the activity of a basolaterally located Na(+)-(n)HCO3-
      cotransporter. The CO2-elicited t-s net flux could also be explained by the
      presence of this transporter and a recirculation of label across the basolateral
      membrane.

PMID- 8983973
TI  - Correlation between autofluorescent debris accumulation and the presence of
      partially processed forms of cathepsin D in cultured retinal pigment epithelial
      cells challenged with rod outer segments.
AB  - The purpose of the present study was to investigate the accumulation of rod outer
      segment (ROS)-derived debris in cultured human retinal pigment epithelial cells
      (RPE). The RPE cell layer is responsible for the phagocytosis and digestion of
      photoreceptor outer segments. Due to the immense volume of photoreceptor-derived
      material processed by the RPE cells, even minor changes in the efficiency of ROS
      processing may cause the accumulation of lipofuscin and photoreceptor derived
      debris. In this work, 17 RPE cultures were established from the globes of eye
      bank donors whose ages ranged from 18 to 79 years. Third passage cultures were
      challenged with bovine ROS and the accumulation of an autofluorescent debris was
      quantified using a flow cytometer. It was demonstrated that ROS challenge greatly
      increased the rate of autofluorescent debris accumulation. The accumulation of
      autofluorescent debris varied significantly from culture to culture. This
      variation was independent of the phagocytosing capacity of individual cultures
      and was not age dependent. To further investigate the factors which may be
      responsible for these differences, the presence of cathepsin D, an aspartic
      protease responsible for 80% of proteolysis of rhodopsin, was analysed by Western
      blot. Although the 34 kDa active form of cathepsin D was found in all cultures,
      in 41% of the cultures higher-molecular-weight forms of cathepsin D were
      additionally present, thus providing a multimer form of cathepsin D in these
      cultures. The rate of autofluorescent debris accumulation in cultures possessing
      a multimer form of cathepsin D was significantly greater (mean 42.3, S.D. +/-
      19.8) than those in cultures having a singlet active form (mean 18.8, S.D. +/-
      5.5) at 34 kDa (Student's t-test, DF = 15, t = 6.834, P < 0.001). The former
      cultures included one from a donor with age related macular degeneration, the
      latter cultures included one from a donor with diabetic retinopathy. This study
      demonstrates that the rate of autofluorescent debris accumulation in cultured RPE
      cells is not age dependent, but is an intrinsic property of the donor RPE cells
      that is possibly related to the presence of a multimer form of the lysosomal
      enzyme cathepsin D.

PMID- 8983974
TI  - Human conjunctival epithelial cells express histamine-1 receptors coupled to
      phosphoinositide turnover and intracellular calcium mobilization: role in ocular
      allergic and inflammatory diseases.
AB  - Dispase-dissociated primary cultures of human conjunctival epithelial (HCE) cells
      were stimulated with histamine and the generation of inositol phosphates
      ([3H]IPs) from [3H]phosphoinositide (PI) hydrolysis and the mobilization of
      intracellular calcium ([Ca2+]i) were studied using ion exchange chromatography
      and Fura-2 fluorescence techniques, respectively. Histamine (100 microM)
      maximally stimulated PI turnover in HCE cells by 210 +/- 10% (n = 21) above basal
      levels and with a potency (EC50) of 3.3 microM (n = 4). Histamine (EC50 = 5.8
      microM, n = 3) rapidly mobilized [Ca2+]i which peaked within 10 sec but which was
      still significantly elevated 20 min after stimulation. The histamine-induced
      [Ca2+]i responses did not desensitize upon repeated applications of histamine.
      The effects of histamine (100 microM) on PI turnover and [Ca2+]i were potently
      antagonized by the H1-antagonists, emedastine (IC50 = 1.6-2.9 nM), triprolidine
      (IC50 = 3.1 nM) and levocabastine (IC50 = 8 nM), but weakly by the H2
      (ranitidine/cimetidine) and H3-(thioperamide) antagonists (IC50s = 10-100
      microM). In conclusion, HCE cells have been shown to possess functional H1
      histamine receptors that couple to inositol phosphates generation which then
      mobilize intracellular calcium. These intracellular signaling mechanisms may be
      intimately linked with the process of inflammatory cytokine secretion from the
      HCE cells after stimulation by histamine released from the conjunctival mast
      cells. The current results strongly suggest that the HCE cells are active
      participants in mediating, and perhaps amplifying, the pro-inflammatory and
      allergic effects of histamine which is released from conjunctival mast cells
      during ocular allergic and inflammatory reactions.

PMID- 8983975
TI  - Age-related accumulation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-
      carboxylic acid in human lens.
AB  - A fluorescent beta-carboline, 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-
      carboxylic acid (MTCA) was identified in human normal lenses and cataractous
      lenses. The mean total amounts of MTCA in normal lenses (n = 7), diabetic
      cataractous lenses (n = 15), and senile cataractous lenses (n = 15) were 0.64 +/-
      0.76 ng, 1.79 +/- 0.94 ng, and 3.66 +/- 1.04 ng, respectively. The MTCA levels in
      human lenses increased linearly with the age of the lenses, and there was a
      significant correlation between the total amount of MTCA in human lenses and the
      age of the lens. In all types of lenses, the concentrations of MTCA in the
      insoluble-protein fraction [pg (mg protein)-1] were significantly higher than
      those in the water-soluble protein fraction. These results suggest that MTCA may
      be one of the age-related fluorogens. In vitro experiments revealed that MTCA, a
      condensation reaction product of tryptophan with acetaldehyde, can be formed in
      the mixture of tryptophan and glucose by low temperature heating. Furthermore,
      the MTCA levels in the homogenate of cataractous lenses were significantly
      increased with the heating time, when the homogenate without addition of glucose
      and tryptophan was heated at 60 degrees C. This indicates that enough material
      such as tryptophan for MTCA formation is present in human cataractous lenses.
      Therefore, it may be that MTCA is formed in human lens. However, we can not rule
      out the possibility that MTCA in the lens may be derived from other sources, and
      deposited in the lens since MTCA is reported to be present in various foodstuffs
      and alcoholic beverages.

PMID- 8983976
TI  - Gap junctions are found between iris sphincter smooth muscle cells but not in the
      ciliary muscle of human and monkey eyes.
AB  - Physiological studies indicate that in primate ciliary muscle there is little or
      no spread of electrical activity from cell to cell. To clarify to what extent
      primate intraocular smooth muscles express the structural correlate of electrical
      coupling, the localization of gap junctions in the ciliary and the iris sphincter
      muscle of human and monkey (Macaca fascicularis) eyes was analysed using
      electronmicroscopy and connexin43 immunocytochemistry. With both methods,
      numerous gap junctions were identified in the iris sphincter of both species,
      while no such junctions were observed between individual smooth muscle cells in
      the ciliary muscle. Both ciliary and iris sphincter smooth muscle cells were
      connected by numerous adherens-type junctions. These results further underline
      that primate ciliary muscle is an atypical smooth muscle which shares many common
      features with striated skeletal muscle.

PMID- 8983977
TI  - Characterization and developmental regulation of avian corneal beta-1,4
      galactosyltransferase mRNA.
AB  - Corneal development involves the synthesis and assembly of a number of
      specialized extracellular matrices. These matrices have distinctive properties
      derived from a unique assembly of collagens, proteoglycans and glycoproteins. The
      synthesis of each of these requires a number of enzymes. By probing a corneal
      cDNA library for genes that appeared to be up-regulated in cornea we have
      isolated a cDNA that represents an mRNA encoding the enzyme beta-1,4
      galactosyltransferase. In cornea, a major function for this enzyme is likely to
      be in the synthesis of the keratan sulfate proteoglycan, lumican. Employing
      quantitative reverse transcript-polymerase chain reaction, we have observed that
      the steady-state level of mRNA for the molecule is elevated during certain stages
      of corneal development. It is also elevated in corneal fibroblasts in culture
      that have a greatly decreased synthesis of the mature lumican molecule. These
      data are consistent with, and complement, studies by others that show a
      corresponding regulation of the lumican core protein during development and in
      corneal fibroblast cultures.

PMID- 8983978
TI  - The properties of retinal pigment epithelial cells in proliferative
      vitreoretinopathy compared with cultured retinal pigment epithelial cells.
AB  - Retinal pigment epithelial (RPE) cells, which proliferate and dedifferentiate
      under several pathological conditions, and cultured RPE cells have been
      considered a good model for comparison. In this investigation, we compared the
      properties of RPE cells in proliferative vitreoretinopathy with that of cultured
      human RPE cells. mRNAs of RPE cells from patients with proliferative
      vitreoretinopathy and from cultured human RPE cells were extracted, and reverse
      transcriptase-polymerase chain reaction was performed. We also examined cells
      that were aspirated from bare RPE surface from a patient with a giant retinal
      tear. We amplified the interleukin-6 gene in the proliferative membranes and
      cultured RPE cells. We also amplified the tyrosinase gene in seven of eight
      proliferative membranes, as well as tyrosinase-related proteins and cellular
      retinaldehyde-binding protein genes, but not the tyrosinase gene in cultured RPE
      cells. The cells aspirated from bare RPE surface showed reduced activity for
      expressing interleukin-6 and tyrosinase genes. The dedifferentiation
      characteristics of cultured RPE cells were different, in that they were less
      active than RPE cells in proliferative membranes for expressing the genes of
      melanogenesis, which are essential for pigment cells. Interleukin-6 and genes
      that were related to melanogenesis were expressed in the proliferative membranes
      and may play an important role in the generation of proliferative
      vitreoretinopathy.

PMID- 8983979
TI  - Modulation of retinal endothelial barrier in an in vitro model of the retinal
      microvasculature.
AB  - The prediabetic/diabetic condition functionally alters the microvascular bed of
      the eye and the breakdown in the transvascular barrier may be produced by changes
      in the retinal endothelial barrier. To better understand how retinal microvessel
      barrier is maintained and is altered in vivo this study applies and extends our
      previously described in vitro permeability technique to study retinal endothelial
      monolayers. The model of the retinal microvasculature consists of retinal
      capillary endothelial cells cultured on porous microcarrier beads and perfused in
      chromatographic 'cell-columns'. This model design relies on indicator-dilution
      techniques to measure the permeability of the retinal endothelial monolayer and
      detects small changes in retinal endothelial permeability produced by treatments.
      Bovine retinal capillary endothelial cells (RCE) were obtained using an
      endothelial selective media. RCE were seeded at 3 x 10(4) cells cm-2 of
      fibronectin-coated gelatin microcarriers. After 7 days of microcarrier culture,
      microcarriers were poured to form columns 0.66 cm in diameter and 1.6 cm in
      length. The cell-column elution patterns of coinjected optically absorbing
      tracers (blue dextran 2 x 10(6) Da; cyanocobalamin 1355 Da; sodium fluorescein
      376 Da) were analysed to estimate the permeability of the RCE monolayers covering
      the microcarriers. Scanning electron microscopic examination showed complete
      monolayer formation on the surface of the microcarriers. We found that baseline
      monolayer permeability averaged 7.57 +/- 0.57 x 10(-5) cm sec-1 for
      cyanocobalamin and 9.29 +/- 0.78 x 10(-5) cm sec-1 for sodium fluorescein (mean
      +/- S.E.M., n = 39). Permeability did not increase over 2 hr of cell-column
      perfusion. Permeability was decreased by 1 micron isoproterenol (n = 3) and
      increased by 1 microgram ml-1 cytochalasin D (n = 5). This is one of the first
      reports of in vitro permeability values for the transport barrier formed by
      retinal microvascular endothelial cells. Furthermore, the endothelial component
      of the retinal barrier is dynamic, and is enhanced by isoproterenol and
      diminished by cytochalasin D.

PMID- 8983980
TI  - Lens tropomodulin: developmental expression during differentiation.
AB  - Lens epithelial cells undergo a dramatic transformation during the process of
      differentiation into elongated fiber cells. The membrane-associated actin
      cytoskeleton is likely to play a critical role in the stabilization and
      maintenance of the highly elongated fiber cell shape. Tropomodulin is a
      tropomyosin-binding protein associated with actin filaments in a variety of
      terminally differentiated cell types where stable actin filament organization is
      required for cell function. We now present results of studies to determine the
      temporal expression of tropomodulin in the developing lens. In situ hybridization
      experiments detected expression of tropomodulin mRNA in the developing mouse lens
      in elongating cells with a pattern similar to that of the fiber specific beta-
      and gamma-crystallins. Tropomodulin mRNA expression first appeared around 11.5
      days post-coitum in elongating cells in the posterior part of the lens vesicle.
      At later stages the signal for tropomodulin was present in the elongating cells
      at the lens equator and in cortical fiber cells; signal was absent from the
      epithelium. To investigate the possible link between tropomodulin expression and
      fiber differentiation we used a well-established lens epithelial explant culture
      system in which fiber differentiation is induced by fibroblast growth factor
      (FGF). Tropomodulin expression was only observed in FGF-treated explants in
      conjunction with morphologic changes characteristic of lens fiber cell
      differentiation. The appearance of tropomodulin during the process of fiber cell
      differentiation suggests that tropomodulin may be important for stabilization
      and/or determination of actin filament length.

PMID- 8983981
TI  - Functional relation between corticonuclear input and movements evoked on
      microstimulation in cerebellar nucleus interpositus anterior in the cat.
AB  - The functional relation between receptive fields of climbing fibres projecting to
      the C1, C3 and Y zones and forelimb movements controlled by nucleus interpositus
      anterior via the rubrospinal tract were studied in cats decerebrated at the pre
      collicular level. Microelectrode tracks were made through the caudal half of
      nucleus interpositus anterior. This part of the nucleus receives its cerebellar
      cortical projection from the forelimb areas of these three sagittal zones. The C3
      zone has been demonstrated to consist of smaller functional units called
      microzones. Natural stimulation of the forelimb skin evoked positive field
      potentials in the nucleus. These potentials have previously been shown to be
      generated by climbing fibre-activated Purkinje cells and were mapped at each
      nuclear site, to establish the climbing fibre receptive fields of the afferent
      microzones. The forelimb movement evoked by microstimulation at the same site was
      then studied. The movement usually involved more than one limb segment. Shoulder
      retraction and elbow flexion were frequently evoked, whereas elbow extension was
      rare and shoulder protraction never observed. In total, movements at the shoulder
      and/or elbow occurred for 96% of the interpositus sites. At the wrist, flexion
      and extension movements caused by muscles with radial, central or ulnar
      insertions on the paw were all relatively common. Pure supination and pronation
      movements were also observed. Movements of the digits consisted mainly of dorsal
      flexion of central or ulnar digits. A comparison of climbing fibre receptive
      fields and associated movements for a total of 110 nuclear sites indicated a
      general specificity of the input-output relationship of this cerebellar control
      system. Several findings suggested that the movement evoked from a particular
      site would act to withdraw the area of the skin corresponding to the climbing
      fibre receptive field of the afferent microzones. For example, sites with
      receptive fields on the dorsum of the paw were frequently associated with palmar
      flexion at the wrist, whereas sites with receptive fields on the ventral side of
      the paw and forearm were associated with dorsiflexion at the wrist.
      Correspondingly, receptive fields on the lateral side of the forearm and paw were
      often associated with flexion at the elbow, whereas sites with receptive fields
      on the radial side of the forearm were associated with elbow extension. The
      proximal movements that were frequently observed also for distal receptive fields
      may serve to produce a general shortening of the limb to enhance efficiency of
      the withdrawal. It has previously been suggested that the cerebellar control of
      forelimb movements via the rubrospinal tract has a modular organisation. Each
      module would consist of a cell group in the nucleus interpositus anterior and its
      afferent microzones in the C1, C3 and Y zones, characterised by a homogenous set
      of climbing fibre receptive fields. The results of the present study support this
      organisational principle, and suggest that the efferent action of a module is to
      withdraw the receptive field from an external stimulus. Possible functional
      interpretations of the action of this system during explorative and reaching
      movements are discussed.

PMID- 8983982
TI  - Analysis of potentials induced in red nucleus neurones from the somaesthetic
      pathway stimulated at the bulbar level.
AB  - A somaesthetic pathway to the magnocellular red nucleus (RNm) via relays other
      than cortico- or cerebello-rubral relays was previously found to exist in the
      cat. At the brainstem level, the ascending spinorubral fibres follow the medial
      lemniscus (LM). The present paper aims at describing in detail and evaluating the
      quantitative importance of the short-latency responses in RNm cells after
      microstimulation performed in the LM through a monopolar electrode. The RNm
      cells, tested intracellularly in cats anaesthetized with alpha-choralose and
      placed in a stereotaxic device, were identified by their antidromic activation to
      stimulation of the rubrospinal tract in the cervical cord. It was established
      that single-shock stimulation below 100 miroA current delivered to the LM induced
      short-lantency postsynaptic potentials (PSPs) in 87% of all the rubrospinal cells
      tested. The responses were indeed due to activation of LM fibres, as demonstrated
      by different tests: the location of the electrode tip in the LM was verified by
      recording, with the same electrode, the potentials evoked by stimulating the
      dorsal columns of the cord. The site was later confirmed histologically. The
      absence of stimulus spread from the LM to the underlying pyramidal tract was
      systematically checked by simultaneously recording the responses evoked in RNm
      cells and in the motor cortex. Monosynaptic excitatory responses (EPSPs) were
      evoked in RNm cells with a minimum stimulating current of less than 20 microA in
      the LM and a mean threshold of 42 microA. Disynaptic inhibitory potentials
      (IPSPs) were evoked in 23% of these cells with single-pulse stimulation. These
      latter responses showed a temporal facilitation with short trains of three
      pulses, which indicated that they were transmitted through inhibitory
      interneurones. Recordings were also performed from presumed LM fibre terminals
      running inside the RNm. The results therefore confirm the existence of strong
      lemniscal projections to RNm and demonstrate that they transmit both excitatory
      and inhibitory messages to rubrospinal cells. As the somaesthetic pathway to the
      RNm was previously found to come from the spinal cord, where it is located in the
      ventral portion, the present results also confirm that the LM is composed of
      fibres originating not only from neurones in the dorsal column nuclei, but also
      from cells placed at the segmental levels of the cord. The presumed sensorimotor
      function of this ascending pathway is discussed.

PMID- 8983983
TI  - NMDA and non-NMDA receptors mediate taste afferent inputs to cortical taste
      neurons in rats.
AB  - Two main subclasses of ionotropic receptors for excitatory amino acids (EAAs), N
      methyl-D-aspartate (NMDA) receptors and non-NMDA receptors, are involved in
      neurotransmission in the cortex of mammals. To examine whether EAAs are
      transmitters at the cortical taste area (CTA) in rats and to elucidate which
      types of the two ionotropic receptors operate at these synapses, we studied the
      effects of microiontophoretic administration of EAA antagonists on the responses
      of 64 taste cortical neurons to four basic taste stimuli in urethane-anesthetized
      rats. Both D-2-amino-5-phosphonovalerate (APV), a selective antagonist for NMDA
      receptors, and 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), a selective
      antagonist for non-NMDA receptors, suppressed most of the taste responses. The
      percentage of neurons suppressed by APV (70.3%) was almost the same as that
      suppressed by CNQX (64.1%). These suppressive effects were independent of the
      effects of background discharges during the prestimulus, water-rinsing period.
      The percentage of neurons suppressed by the antagonists did not differ between
      any pairs of taste stimuli. The number of neurons possessing both receptors was
      larger in the granular insular area (area GI), one of the two CTAs, than in the
      dysgranular insular area (area DI). In addition, taste responses were suppressed
      by CNQX or by both APV and CNQX in area GI in a significantly larger number of
      layer V neurons than in area DI. The present results indicate that normal
      excitatory transmission of taste afferents in the CTA in rats was mediated by
      both NMDA and non-NMDA receptors. The finding that a large fraction of neurons in
      the CTA in rats mediated taste information through NMDA receptors in normal
      transmission might be related to the higher potency of the plasticity observed in
      the CTA.

PMID- 8983984
TI  - An in vivo electrophysiological investigation of group Ia afferent fibres and
      ventral horn terminations in the cat spinal cord.
AB  - An extracellular microstimulation technique has been used to investigate and
      compare the properties of group I primary afferent myelinated fibres in the
      dorsal column and group Ia unmyelinated terminations in the lumbar spinal cord of
      cats anaesthetised with pentobarbitone sodium. Fibres were distinguished from
      terminations on the basis of location, anodic blocking factor and sensitivity to
      GABAA mimetics. The recovery curves of threshold following an orthodromic impulse
      provided an estimate of both action potential duration and rate of
      repolarization. The action potentials of group Ia terminations were of briefer
      duration (by a factor of approximately 2) with more rapid rates of repolarization
      (factor of approximately 3) than those of the myelinated fibres. The prolongation
      of termination but not fibre action potentials by microelectrophoretic
      tetraethylammonium and 4-aminopyridine indicated the presence of voltage
      activated potassium channels in the termination membrane. Differences in the
      effects on Ia termination action potentials of depolarizations (reductions in
      threshold) associated with a preceding action potential, synaptically released
      GABA, microelectrophoretic piperidine-4-sulphonic acid or DL-homocysteic acid
      suggest that an increase in termination membrane conductance is the major factor
      in the reduction of transmitter release during the activation of presynaptic
      GABAA receptors.

PMID- 8983985
TI  - Changes in reciprocal and transjoint inhibition induced by muscle fatigue in man.
AB  - The effects of localised muscle fatigue on group I reflex pathways were studied
      in the human upper limb. Activation of group I afferents originating from biceps
      and extensor carpi radialis (ECR) resulted in an inhibition of flexor carpi
      radialis (FCR) motoneurones, probably through a disynaptic pathway. Reciprocal
      inhibition (from ECR to FCR) and transjoint inhibition (from biceps to FCR) were
      compared before and during localised fatigue induced in the muscle from which
      group I afferents originated. Fatigue of wrist extensors did not modify the
      reciprocal inhibition, while during fatigue of elbow flexors the transjoint
      inhibition was less pronounced. This striking difference between reciprocal and
      transjoint inhibition is discussed in relation to the pattern of diffusion of
      voluntary contractions during fatigue in the human upper limb.

PMID- 8983986
TI  - Development of human precision grip. V. anticipatory and triggered grip actions
      during sudden loading.
AB  - When an object held by a precision gripis subjected to an abrupt vertical load
      perturbation, somatosensory input from the digits triggers an increase in grip
      force to restore an adequate safety margin, preventing frictional slips. In
      adults the response occurs after a latency of 60-80 ms. In the present study,
      children from 2 years old upward and adults grasped and lifted an object using a
      precision grip. Sudden, unpredicted increases in load force (tangential to the
      grip surfaces) were induced by the experimenter by dropping a small disc on to a
      receptacle attached to the object. The impact elicited a grip force response
      which in young children had a longer latency and a smaller amplitude than was
      seen in adults. The grip response latency gradually become shorter and its
      amplitude increased with increasing age, reaching adult values at 6-10 years. The
      muscle activity underlying the response could have several bursts. The adults
      showed one brisk response, appearing 40-50 ms after impact, in extrinsic and
      intrinsic hand muscles, while younger children also exhibited a short-latency
      burst, appearing about 20 ms after impact. It is suggested that the short-latency
      response was mediated via spinal pathways, and that these pathways are disengaged
      by supraspinal centers during development. In a predictable loading situation,
      when subjects dropped the disc themselves into the receptable using the
      contralateral hand, they changed strategy. Adults induced a well-timed
      anticipatory grip force increase prior to the impact that was scaled to the
      weight of the object. The youngest children did not time the force increase
      properly in relation to the impact. Yet, they could scale their anticipatory grip
      force increase with respect to the weight of the dropped disc. This suggests a
      well-developed capacity to use information about the weight of objects held by
      one hand to parameterize a programmed force output to the other hand.

PMID- 8983988
TI  - Adaptational and learning processes during human split-belt locomotion:
      interaction between central mechanisms and afferent input.
AB  - Split-belt locomotion (i.e., walking with unequal leg speeds) requires a rapid
      adaptation of biomechanical parameters and therefore of leg muscle
      electromyographic (EMG) activity. This adaptational process during the first
      strides of asymmetric gait as well as learning effects induced by repetition were
      studied in 11 healthy volunteers. Subjects were switched from slow (0.5 m/s)
      symmetric gait to split-belt locomotion with speeds of 0.5 m/s and 1.5 m/s,
      respectively. All subjects were observed to adapt in a similar way: (1) during
      the first trial, adaptation required about 12-15 strides. This was achieved by an
      increase in stride cycle duration, i.e., an increase in swing duration on the
      fast side and an increase in support duration on the slow side. (2) Adaptation of
      leg extensor and flexor EMG activity paralleled the changes of biomechanical
      parameters. During the first strides, muscle activity was enhanced with no
      increase in coactivity of antagonistic leg muscles. (3) A motor learning effect
      was seen when the same paradigm was repeated a few minutes later--interrupted by
      symmetric locomotion--as adaptation to the split-belt speeds was achieved within
      1-3 strides. (4) This short-time learning effect did not occur in the "mirror"
      condition when the slow and fast sides were inverted. In this case adaptation
      again required 12-15 strides. A close link between central and proprioceptive
      mechanisms of interlimb coordination is suggested to underlie the adaptational
      processes during split-belt conditions. It can be assumed that, as in quadrupedal
      locomotion of the cat, human bipedal locomotion involves separate locomotor
      generators to provide the flexibility demanded. The present results suggest that
      side-specific proprioceptive information regarding the dynamics of the movement
      is necessary to adjust the centrally generated locomotor activity for both legs
      to the actual needs for controlled locomotion. Although the required pattern is
      quickly learned, this learning effect cannot be transferred to the contralateral
      side.

PMID- 8983987
TI  - Haptic localization and the internal representation of the hand in space.
AB  - As the hand actively explores the environment, contact with an object leads to
      neuronal activity in the topographic maps of somatosensory cortex. However, the
      brain must combine this somatotopically encoded tactile information with an
      internal representation of the hand's location in space if it is to determine the
      position of the object in three-dimensional space (3-D haptic localization). To
      investigate the fidelity of this internal representation in human subjects, a
      small tactual stimulator, light enough to be worn on the subject's hand, was used
      to present a brief mechanical pulse (6-ms duration) to the right index finger
      before, during, or after a fast, visually evoked movement of the right hand. In
      experiment 1, subjects responded by pointing to the perceived location of the
      mechanical stimulus in 3-D space. Stimuli presented shortly before or during the
      visually evoked movement were systematically mislocalized, with the reported
      location of the stimulus approximately equal to the location occupied by the hand
      90 ms after stimulus onset. This pattern of errors indicates a representation of
      the movement that fails to account for the change in the hand's location during
      somatosensory delays and, in some subjects, inaccurately depicts the velocity of
      the actual movement. In experiment 2, subjects were instructed to verbally
      indicate the perceived temporal relationship of the stimulus and the visually
      evoked movement (i.e., by reporting whether the stimulus was presented "before,"
      "during," or "after" the movement). On average, stimuli presented in the 38-ms
      period before movement onset were more likely to be perceived as having occurred
      during rather than before the movement. Similarly, stimuli in the 145-ms period
      before movement termination were more likely to be perceived as having occurred
      after rather than during the movement. The analogous findings of experiments 1
      and 2 indicate that the same inaccurate representation of dynamic hand position
      is used to both localize tactual stimuli in 3-D space and construct the
      perception of arm movement.

PMID- 8983989
TI  - The coordination between trunk and arm motion during pointing movements.
AB  - The coordination between the trunk and arm of six subjects was examined during
      unrestrained pointing movements to five target locations. Two targets were within
      arm's length, three were beyond. The trunk participated in reaching primarily
      when the target could not be attained by arm and scapular motion. When the trunk
      did contribute to hand transport, its motion started simultaneously with arm
      movement and continued until target contact. Redundancy in the degrees of freedom
      used to execute the movement had no effect on the configuration of joints and
      segments used to attain a specified target; no difference in variability was
      noted regardless of whether redundancy existed. However, different configurations
      were used to achieve the same wrist coordinates along a common endpoint path,
      depending on the final position of the hand. The addition of trunk flexion,
      rotation and scapular motion did not alter the coupling between the elbow and
      shoulder joints and had no effect on the path of the hand or the smoothness of
      its velocity profile. Thus, trunk motion was integrated smoothly into the
      transport phase of the hand. As the trunk's contribution to hand transport
      increased, it played a progressively greater role in positioning the hand close
      to the target during the terminal stage of the reach. Of the movement components
      measured, trunk flexion was the last component to complete its motion when target
      reaches were made beyond arm's length. Hence, the trunk not only acts as a
      postural stabilizer during reaching, but becomes an integral component in
      positioning the hand close to the target.

PMID- 8983990
TI  - Visual and visuomotor performance in dyslexic children.
AB  - The present study was designed to compare the performance of nine dyslexic boys
      and nine age- and IQ-matched controls on tasks which presumably tap visual
      functions dependent on the subcortical magnocellular (M) pathway (flicker
      sensitivity) and the cortical dorsal stream (stereoacuity, structure-from-motion,
      visuomotor control). Increasing evidence suggests that dyslexics experience
      impairments in M-system functioning. In keeping with previous work supporting
      this conclusion, dyslexic subjects in the present study were found to have
      reduced sensitivity to flicker relative to controls. Given that the M system
      provides the predominant input to the dorsal stream, it was expected that reduced
      functioning of the M system in dyslexics would result in disruptions of functions
      related to this cortical visual pathway. Indeed, dyslexic subjects in the present
      study were found to be less efficient at recognizing structure-from-motion and
      less accurate at grasping objects precisely. They also showed a mild impairment
      in stereoacuity. These results, then, lend some support to the hypothesis that
      dyslexic individuals should show deficiencies on tasks dependent on dorsal stream
      processing of visual information.

PMID- 8983992
TI  - An audio-visual convergence area in the human brain.
AB  - By recording the magnetic field of the human brain while simultaneously
      presenting light to the eye and sound to the ear we have identified a brain
      region where auditory and visual signals converge. The location of this region is
      close to primary auditory cortex and far from primary visual cortex.

PMID- 8983991
TI  - Interference between saccadic eye and goal-directed hand movements.
AB  - The aim of the present study was to investigate the nature of the interference
      effect when the eye is accompanied by a goal-directed hand movement rather than
      when the eye moves alone. Latencies of eye and hand movements in response to
      small and large visual target stimuli were measured while employing dual-task
      methodology. Experiments 1 and 2 were designed to investigate whether the
      interference effect is related to a specific temporal bottleneck, i.e. the eye
      and hand motor systems share limited available processes at a specific point in
      time. The findings of robust interference effects independent of the temporal
      organization of eye and hand contradicted this notion. The interference effect
      was not present in experiment 3, where response preparation and target
      localization mechanisms were limited by providing subjects with advance
      information about target position. Experiment 4 employed randomized target
      positions again and highly salient stimuli, the latter only limiting target
      localization processes. The absence of an interference effect adds weight to the
      argument that visual spatial attentional mechanisms involved in target
      localization constitute the locus of the interference. Neurophysiological
      implications of these findings are discussed.

PMID- 8983993
TI  - Pinch force matching errors predicted by an equilibrium-point model.
AB  - Varying the size or stiffness of an external load often results in systematic
      grasp force or finger span matching errors, typically judged via contralateral
      matching. In the present study, subjects squeezed compliant or rigid manipulanda
      in each hand using three-finger pinch in order to generate, and simultaneously
      match, a reference force indicated by a visual cue. Subjects were not informed
      which hand was the reference and were given only 1 s to make a match. Under these
      conditions, subjects appeared to match central commands rather than perceived
      force. Forces were always exaggerated when squeezing an isometric load to match a
      compliant load and were too small when matching a compliant load to an isometric
      load. The matching errors were largest for the most compliant spring and
      increased with the reference force. When the loads were symmetric (e.g., both
      compliant), errors were small, but subjects persistently squeezed slightly harder
      with the left (non-dominant) hand. Apart from the left-hand bias, the matching
      results agree quantitatively and in detail with the predictions of an equilibrium
      point model (the lambda model), in which central commands shift the rest length
      of spring-like muscle. The matching data are fit best assuming that the muscle's
      compliance characteristic is an accelerating function, in agreement with previous
      direct measurements of pinch stiffness.

PMID- 8983994
TI  - The role of the left somatosensory cortex in human hand movement.
AB  - Hemispheric dominance for motor control in the human brain is still unclear. Here
      we propose asymmetric sensorimotor integration during human hand movements. We
      investigated the dexterity of hand movements and related sensory functions in
      four right-handed patients with cerebrovascular lesions in the postcentral gyrus.
      To clarify the distributions of cortical damage, semiquantitative analysis of
      regional cerebral blood flow (rCBF) was performed using single photon emission
      computed tomography (SPECT), and a three-dimensional surface display was
      generated from SPECT. Scores on motor and sensory tasks and rCBF values in the
      patients were compared with those in control subjects. All patients presented
      with asymmetric clumsiness of complex finger movements, in association with
      impairments of combined sensations such as stereognosis. These findings were
      indicative of a disorder of sensory information processing necessary to guide the
      movements. Two patients with left hemispheric damage showed bilateral clumsy
      hands, predominating on the right side, while the other two patients with right
      hemispheric damage showed only a left clumsy hand. In agreement with asymmetric
      clumsiness, measurement of rCBF along with a three-dimensional surface display
      revealed cortical hypoperfused areas, mainly in the perirolandic cortices,
      comprising the primary motor and somatosensory cortices. Perirolandic cortical
      hypoperfusion was bilateral in the two patients with bilateral clumsy hands, but
      only on the right side in the other two patients with left clumsy hands. These
      results suggest a dominant role of the left somatosensory cortex in sensorimotor
      integration for complex finger movements of humans.

PMID- 8983995
TI  - The role of active forces and intersegmental dynamics in the control of limb
      trajectory over obstacles during locomotion in humans.
AB  - The focus of this paper is to examine the contributions of active and passive
      forces in the control of limb trajectory over obstacles during locomotion.
      Kintetic analyses of the swing phase of locomotion were carried out to determine
      the power profiles at various joints and to parcel the joint moments into moments
      due to muscle action, gravitational force and motion-dependent terms. The
      analyses revealed that toe elevation over the obstacles was achieved primarily by
      flexing at the hip, knee and ankle joint. Power analyses showed that
      translational energy applied at the hip joint and rotational energy applied at
      the knee joint were modulated as functions of obstacle height. This demonstrates
      that increased hip and ankle joint flexion are achieved not through active muscle
      action but rather through passive forces induced by translational action at the
      hip (representing contribution by the stance limb muscles) and rotational action
      at the knee joint. Parcelling the joint moment terms into various components
      clearly shows how the nervous system exploits intersegmental dynamics to simplify
      control of limb elevation over obstacles and minimize energy costs.

PMID- 8983996
TI  - Attenuation of high-voltage-activated Ca2+ current run-down in rat hippocampal
      CA1 pyramidal cells by NaF.
AB  - Calcium currents in CA1 neurons from rat hippocampus were studied with the whole
      cell, patch-clamp technique. Under control conditions high-voltage-activated
      (HVA) calcium currents activated from membrane potentials of -80 mV and -40 mV
      underwent "run-down". The rate of run-down of the current activated from -40 mV
      was significantly attenuated by inclusion of the G-protein activator NaF (1 mM)
      in the pipette and also irreversibly attenuated by brief batch application of NaF
      (10 mM). This effect was significantly reduced by inclusion of high (10 mM)
      ethyleneglycoltetraacetate (EGTA) concentrations in the pipette, suggesting an
      involvement of calcium-dependent processes. It is suggested that activation of
      guanine nucleotide-binding proteins by NaF leads to a long-lasting attenuation of
      HVA calcium current run-down in hippocampal CA1 cells.

PMID- 8983997
TI  - Evidence for high-velocity smooth pursuit in the trained cat.
AB  - It is generally accepted that in cats smooth pursuit velocity of the eye never
      exceeds a few degrees per second. This is in contrast with observations in
      primates, where smooth pursuit velocity can reach values as high as 100
      degrees/s. Cats were trained to fixate and pursue spots of light appearing on a
      translucent screen. Spots were moved in the horizontal and vertical planes at
      different constant velocities up to 80%. Eye position was recorded with the
      scleral search coil technique. Naive cats did not pursue moving targets with high
      efficiency. Smooth eye movement velocity saturated at 5 degrees/s. After a few
      days of training, smooth-pursuit eye velocity increased with target velocity and
      saturated at 25 degrees/s on average. However, velocities twice as high have been
      observed frequently. When the target was unexpectedly extinguished, smooth eye
      movement velocity dropped to values close to 0 degree/s in approximately 350 ms.
      After a short training period (usually 5 times the same target presentation), the
      eye continued to move smoothly until the target reappeared. These data suggest
      that smooth pursuit eye movements of the cat are qualitatively similar to those
      of primates, but reach lower velocities and are more variable in their
      characteristics.

PMID- 8983999
TI  - 35th annual meeting of the Society of Toxicology. Anaheim, California, March 10
      14, 1996. Abstracts.

PMID- 8983998
TI  - Special issue: A tribute to Milton W. Brightman.

PMID- 8984000
TI  - Detection of cytosine methylation and mapping of a gene influencing cytosine
      methylation in the genome of Citrus.
AB  - A new method was developed to detect DNA methylation in the Citrus genome using
      random amplification coupled with restriction enzyme digestion. Genomic DNA from
      Citrus grandis (L.) Osb., Poncirus trifoliata (L.) Raf., and their F1 hybrid was
      amplified using 7 individual 10-mer random primers. Prior to amplification the
      DNA templates were digested with 2 pairs of restriction endonucleases (HpaII-MspI
      and (or) Sau3AI-NdeII) with different sensitivities to cytosine methylation and
      after PCR amplification their amplified products were further digested with the
      same enzymes. Using this method, it was possible to detect 28 methylation events
      involving 23 amplified bands with the 7 random primers and 2 pairs of enzymes. A
      methylation polymorphism was found at a Sau3AI site in a 1.2-kb band amplified
      with one primer. One locus influencing cytosine methylation at this restriction
      site was identified through genetic analysis of a BC1 population between C.
      grandis and P. trifoliata and was mapped to linkage group IV using an already
      developed core map. This technique for detecting methylation and methylation
      polymorphisms is simple and should be applicable to any eukaryotic species and to
      many situations where it is desirable to determine whether a sequence is
      methylated.

PMID- 8984001
TI  - The molecular structure, chromosomal organization, and interspecies distribution
      of a family of tandemly repeated DNA sequences of Antirrhinum majus L.
AB  - Monomers of a major family of tandemly repeated DNA sequences of Antirrhinum
      majus have been cloned and characterized. The repeats are 163-167 bp long,
      contain on average 60% A+T residues, and are organized in head-to-tail
      orientation. According to site-specific methylation differences two subsets of
      repeating units can be distinguished. Fluorescent in situ hybridization revealed
      that the repeats are localized at centromeric regions of six of the eight
      chromosome pairs of A. majus with substantial differences in array size. The
      monomeric unit shows no homologies to other plant satellite DNAs. The repeat
      exists in a similar copy number and conserved size in the genomes of six European
      species of the genus Antirrhinum. Tandemly repeated DNA sequences with homology
      to the cloned monomer were also found in the North American section Saerorhinum,
      indicating that this satellite DNA might be of ancient origin and was probably
      already present in the ancestral genome of both sections.

PMID- 8984002
TI  - Simple sequence repeats for germplasm analysis and mapping in maize.
AB  - Simple sequence repeats (SSRs) are a relatively new class of DNA markers
      consisting of short runs of tandemly repeated sequence motifs evenly distributed
      throughout eukaryotic genomes. Owing to the high rate of variation in the number
      of repeat units, the polymorphism level shown by SSRs is high. Furthermore, they
      are easy to analyze by means of the polymerase chain reaction, using flanking
      unique sequence primers. In order to establish the utility of SSR markers for
      genetic mapping and for the analysis of corn germplasm, corn genomic libraries
      were constructed and screened for clones containing dinucleotide and
      trinucleotide repeats. One hundred and fifty clones were isolated and 34 of them
      were used in this study to analyze 15 (AG)n repeats, 15 (AC)n repeats, and 4
      trinucleotide repeats. Twelve corn inbred lines, representing 87% of the RFLP
      alleles present in a collection of public corn cultivars, were used to assess the
      information content of the SSR markers. The expected heterozygosity of each SSR
      marker was compared with the expected heterozygosity of 100 different RFLP
      markers. The stability of SSRs was also tested through segregation analysis on an
      existing mapping population.

PMID- 8984003
TI  - Molecular cloning and characterization of an unusually large intergenic spacer
      from the Nor-B2 locus of hexaploid wheat.
AB  - An allelic rDNA variant from the Nor-B2 locus of 'Bezostaya' wheat that forms an
      especially active nucleolus was cloned and characterized. It carries an unusually
      large intergenic spacer compared with rDNA units in most other wheat genotypes.
      The additional intergenic length is in the array of 135-bp A repeats and not in
      other internal repeats. These A repeats have sequences nearly identical to other
      A repeats described for other alleles. It is suggested therefore that the more
      active Nor-B2 locus of 'Bezostaya' may be due to the constituent rDNA units
      possessing a larger array of A repeats.

PMID- 8984004
TI  - Segregation analysis of the testis-determining autosomal trait, Tda, that differs
      between the C57Bl/6J and DBA/2J mouse strains suggests a multigenic threshold
      model.
AB  - The testis-determining autosomal trait (Tda) of the mouse was uncovered when the
      Y chromosome of the poschiavinus variety of Mus musculus domesticus was
      introduced into the C57BL/6J laboratory strain background. Testis development is
      normal in the F1 generation but, in the backcross and subsequent crosses to
      C57BL/6J females, XY individuals with the poschiavinus Y chromosome expressed
      bilateral ovaries or various combinations of an ovotestis with a contralateral
      ovary or testis or bilateral ovotestes and few had testes bilaterally. In other
      strain backgrounds, such as DBA/2J, XY individuals with the poschiavinus Y
      chromosome always expressed normal testes bilaterally. The first breeding
      analysis of this difference in the interaction of strain background with the
      poschiavinus Y chromosome suggested that the Tda trait was due to a single gene,
      but attempts to map it failed. We constructed two strains of C57BL/6J and DBA/2J
      that are consomic for the poschiavinus Y chromosome in order to conduct a
      segregation analysis of the Tda trait. In the C57BL/6J.Y-POS consomic strain,
      liability to express incomplete testis development is normally distributed and
      thresholds in development specify the probability of different classes of ovary,
      ovotestis, and testis combinations. Testis development is complete in the
      DBA/2J.Y-POS consomic strain. We demonstrated previously that the Tda trait of
      C57BL/6J is recessive to that of DBA/2J and the segregating first backcross
      generation of embryos rejected the single-gene model. We have extended our
      analysis to a F2 generation of embryos that also rejects a single-gene model. We
      also report a test mating analysis of the first backcross generation. It was
      initiated to provide an independent assessment of the single-gene model, but the
      analysis of the distribution of test mating results suggests that the difference
      in the Tda trait between C57BL/6J and DBA/2J may be due to a small number of
      loci, possibly four or five, and that the phenotypic effect between loci may be
      additive.

PMID- 8984005
TI  - Cloning and mapping of variety-specific rice genomic DNA sequences: amplified
      fragment length polymorphisms (AFLP) from silver-stained polyacrylamide gels.
AB  - An efficient technique for cloning DNA from silver-stained denaturing
      polyacrylamide gels was developed to allow the isolation of specific bands
      obtained from selective restriction fragment amplification (SRFA). This method
      proved as reliable as cloning radioactively labelled SRFA bands from the same
      gels. Rice DNA was used as a template, both with and without [32P]dCTP, using the
      same PCR profiles. Amplified products were separated using denaturing
      polyacryamide gel electrophoresis and visualized either by silver staining of
      gels or by autoradiography of 32P-labelled products. We cloned specific
      polymorphic SRFA bands directly from the denaturing polyacrylamide gels with one
      round of PCR amplification and confirmed that the sequences of the bands from
      silver-stained gels were identical to the corresponding 32P-labelled bands. The
      bands that were chosen represented amplified fragment length polymorphisms
      (AFLPs) between japonica and indica rice varieties. We studied the ability of two
      cloned AFLP bands to serve as heritable genetic markers by mapping them as RFLPs
      in an interspecific rice population and found that they represented single-copy
      DNA at unique loci in the rice genome.

PMID- 8984006
TI  - Molecular and biochemical characterization of two nucleoside diphosphate kinase
      cDNA clones from Flaveria bidentis.
AB  - Two nucleoside diphosphate kinase cDNA clones have been isolated from Flaveria
      bidentis by immunoscreening of an expression library with a polyclonal antibody
      raised against Flaveria chloraefolia flavonol 3-sulfotransferase (F3-ST). The
      clones represent members of a small multigene family in this species. The
      nucleotide sequences of the two cDNA clones show a high degree of sequence
      similarity to other reported nucleoside diphosphate kinases (NDPKs), including
      the putative human tumor suppressor gene NM23 and the Drosophila regulatory gene.
      When these cDNA clones were expressed in Escherichia coli, their gene products
      exhibited NDPK enzymatic activity. The immunocross reaction of the clones with
      the antibody raised against the F3-ST suggests a common immuno-epitope and a
      similarity of a nucleotide binding site for the two proteins.

PMID- 8984007
TI  - Chromosomal and genomic organization of Ty1-copia-like retrotransposon sequences
      in the genus Avena.
AB  - A cloned repetitive sequence, pAvKB30, obtained from an Avena vaviloviana (AB
      genome) genomic library, along with two polymerase chain reaction products
      derived from the conserved region of the reverse transcriptase (RT) gene of
      retrotransposons, were characterized molecularly and cytologically. The cloned
      DNA fragment was a dispersed repeat present in all Avena species used in this
      study (A. strigosa, A. clauda, A. vaviloviana, A. magna, and A. sativa). The
      fragment was sequenced (210 bp) and found to be 69.5% homologous to part of WIS-2
      1A, and 60.5% homologous to the leader sequence of BARE-1; both of these elements
      have been characterized as Ty1-copia-like retrotransposons in wheat and barley,
      respectively. In situ hybridization of pAvKB30 to diploid, tetraploid, and
      hexaploid oat species revealed that the probe is present on both arms of all
      chromosomes (A, B, C, and D genomes) but is excluded from their centromeric and
      nucleolar organizer regions. By using double in situ hybridization in hexaploid
      A. sativa (ACD genome), pAvKB30 was found to be present in lower copy numbers in
      C-genome chromosomes compared with A- and D-genome chromosomes. Furthermore,
      under low stringency conditions, pAvKB30 hybridized on Southern blots containing
      barley, wheat, rye, and Arrhenatherum DNA. However, under high stringency
      conditions, it hybridized only on Arrhenatherum DNA, which is considered to be
      the genus most closely related to Avena. All Avena species included in this study
      yielded a PCR product when the primers from the RT domain of retrotransposons
      were used. Two products, rtA, obtained by using A. strigosa (A(s) genome) as
      template, and rtC, obtained by using A. clauda (Cp genome) as template, gave
      Southern and in situ hybridization results similar to pAvKB30, but each was more
      abundant in its genome of origin.

PMID- 8984008
TI  - DNA sequences of RAPD fragments in artiodactyls.
AB  - A bovine RAPD profile, generated by a 10-mer primer, was analysed by sequencing
      the major fragments. Three of four different fragments showed homologies to
      previously characterized mammalian sequences. One was 61-66% identical to LINE
      sequences and another was 78.5% identical to a human chromosome 2 sequence tagged
      site. The third fragment was 93.1% identical to the human type 2 inositol 1,4,5
      trisphosphate receptor gene. This fragment had counterparts in white-tailed deer
      and reindeer; fragments of slightly different size in these species showed high
      sequence similarity and the size differences were due to varying numbers of
      dinucleotide microsatellite repeats inside the fragment.

PMID- 8984009
TI  - A novel set of uncoordinated mutants in Caenorhabditis elegans uncovered by cold
      sensitive mutations.
AB  - A set of uncoordinated (Unc) cold-sensitive (cs) mutants was isolated at a
      stringent condition of 11 degrees C. About half of the 13 independently isolated
      cs-Unc mutants were alleles of three X-linked Unc mutants that exhibited the
      "kinker" phenotype. The remaining four isolates identified new mutants that
      exhibited "kinker," "coiler," or severe paralytic phenotypes. The temperature
      sensitive period (TSP) for each gene was determined. As a homozygous or
      heterozygous dominant, unc-125 exhibited a TSP throughout all stages of
      development. Its severe paralysis was immediately observed upon a shift down to
      11 degrees C and reversed upon a shift up to 23 degrees C. The reversible
      thermolability of the unc-125 gene product indicated that it may function in a
      multicomponent process involved in neuro-excitation.

PMID- 8984010
TI  - DNA regions flanking the major Arabidopsis thaliana satellite are principally
      enriched in Athila retroelement sequences.
AB  - An analysis of Arabidopsis thaliana heterochromatic regions revealed that genomic
      sequences immediately flanking the major 180 bp satellite are essentially made of
      middle repetitive sequences and that most of these sequences correspond to
      defective Athila retroelements. Using YAC and lambda clones, we evaluated the
      distribution of Athila elements in the Arabidopsis genome and showed that,
      despite the presence of numerous euchromatic copies, these elements are
      especially concentrated in or near heterochromatic regions. Sequencing of the
      various DNA transitions between satellite and Athila repeats provides strong
      evidence that most of the heterochromatic elements retrotransposed directly into
      180 bp satellite clusters.

PMID- 8984011
TI  - Endoscopic retrograde cholangiopancreatography and acute pancreatitis.

PMID- 8984012
TI  - Diverticular disease and chronic idiopathic inflammatory bowel disease:
      associations and masquerades.

PMID- 8984013
TI  - Combination of laser treatment and intraluminal radiotherapy for malignant
      dysphagia.
AB  - BACKGROUND: Laser treatment for malignant dysphagia is limited by recurrent
      intraluminal tumour requiring repeated treatment at four to eight week intervals.
      AIMS: To reduce the need for follow up treatment and to improve survival,
      patients successfully palliated by laser were treated with intraluminal
      radiotherapy. PATIENTS: 32 patients with inoperable oesophageal carcinoma (18
      adeno and 14 squamous cell carcinoma). METHODS: The patients were initially
      palliated by a median of three laser treatments. They were then treated with
      intraluminal radiotherapy, receiving 10-15 Gy at 1 cm from the source as a single
      treatment with the Selectron system. Patients with squamous cell carcinoma also
      received external radiotherapy (30 to 50 Gy). RESULTS: After the radiotherapy
      nine patients survived a median of 22 (range 4-40) weeks without requiring any
      further endoscopic treatment. The remaining patients survived a median of 40
      (range 4-102) weeks and required a median of three follow up endoscopic
      treatments over that time. Eleven patients developed fibrous strictures with no
      intraluminal tumour and were treated by dilatation. Twelve patients required
      dilatation and repeat laser therapy for a combination of fibrous stricture and
      recurrent intraluminal tumour. Six patients eventually required Atkinson tubes.
      CONCLUSIONS: The combination of laser treatment with intraluminal radiotherapy
      provides good palliation and may reduce the need for repeated endoscopic
      treatment. Fibrous stricture formation is a common complication.

PMID- 8984014
TI  - Influence of surgery on deglutitive upper oesophageal sphincter mechanics in
      Zenker's diverticulum.
AB  - BACKGROUND/AIMS: To evaluate the role of upper oesophageal sphincter (UOS)
      compliance in dysphagia, the functional consequences of surgery were evaluated in
      eight patients with pharyngeal diverticula. The study examined the hypotheses
      that hypopharyngeal intrabolus pressure is an indicator of UOS compliance and
      that UOS opening and intrabolus pressure are normalised by surgery. METHODS: In
      eight patients and nine healthy controls, we measured the timing of swallow
      events, UOS relaxation, maximal UOS dimensions, intrabolus pressure, and trans
      sphincteric bolus flow rates by simultaneous videoradiography and pharyngeal
      manometry. RESULTS: Bolus flow rates were not changed by surgery. Surgery
      significantly increased UOS opening (p = 0.0001) and reduced hypopharyngeal
      intrabolus pressure (p = 0.0001). The slope of the relation between sphincter
      area and intrabolus pressure was steeper in patients than controls and was
      normalised by surgery. Surgery had minor effects on basal UOS tone and timing of
      swallow events. CONCLUSIONS: Upper oesophageal sphincter compliance is poor in
      Zenker's diverticulum and is normalised by surgery. Hypopharyngeal intrabolus
      pressure, which correlates with resistance to trans-sphincteric bolus flow, is a
      useful indicator of UOS compliance. Intrabolus pressure may be a predictor of
      outcome after myotomy in pharyngeal dysphagia. Cricopharyngeal myotomy is a
      mandatory component of surgery for Zenker's diverticulum.

PMID- 8984015
TI  - Audit of the outcome of peptic ulcer disease diagnosed 10 to 20 years previously.
AB  - METHODS/AIMS: During 1993-1994 an audit of the outcomes of a consecutive series
      of peptic ulcer patients, first diagnosed endoscopically between 1972-1983, was
      carried out. Three hundred and thirty six patients fitting the entry criteria
      were identified, 46 had died in the interval, and 44 were lost to follow up,
      leaving 246 available for evaluation. All patients completed questionnaires on
      their current symptomatic state, drug treatment, and details of any operations
      they had undergone since their original diagnosis. In addition they were asked to
      indicate, on an analogue scale, their overall assessment of how their ulcer
      problem was affecting them at the time of the review. Where available hospital
      records were obtained and analysed for any further admissions and the results of
      any further endoscopies. RESULTS: Of the 246 patients, 158 were men and 88
      female. Duodenal ulcers (DU) were present in 204 and gastric ulcers (GU) in 51
      (nine had both a DU and GU). Since the diagnosis 65 patients had undergone
      surgical treatment: 44 for poor ulcer control, nine for pyloric stenosis, nine
      for a perforation, one for a major gastrointestinal bleed, and two for a gastric
      carcinoma developing within two years of the diagnosis of a GU. The overall
      incidence of ulcer complications during this follow up period (excluding the
      carcinomas) was 7.7%. Initial medical treatment was with histamine H2 blockade in
      234 patients--87.4% cimetidine (C) and 11% ranitidine (R)--with other agents in
      the remainder. At follow up 176 patients were still receiving medical treatment
      (C, 71%: R, 22%, other, 7%) including 30 who had previously undergone a
      definitive surgical procedure. Dyspeptic symptoms were recorded in 50.4% of the
      patients, abdominal pain being the commonest complaint. There was a significant
      relation between abdominal pain and the analogue scores provided by the patients
      with significantly more (p = 0.02) of those who had undergone surgical treatment
      recording this as a continuing problem (44.6% v 36%). CONCLUSION: There is no
      evidence provided by this study that, in these patients, their ulcer disease is
      undergoing spontaneous remission with time.

PMID- 8984016
TI  - Scintigraphic measurement of gastric emptying and ultrasonographic assessment of
      antral area: relation to appetite.
AB  - BACKGROUND: Ultrasound measurement of gastric emptying has potential advantages
      over scintigraphy, but there is little information about its accuracy. AIMS: The
      relation between ultrasonographic measurements of antral area and (a)
      scintigraphic measurements of gastric emptying and intragastric distribution of
      liquids (b) postprandial satiation, were evaluated. SUBJECTS: Seven normal
      volunteers were studied. METHOD: Each subject drank 75 g dextrose dissolved in
      350 ml of water (300 kcal) or beef soup (20 kcal), both labelled with technetium
      99m sulphur colloid on separate days and had measurement of gastric emptying by
      scintigraphy and ultrasound. RESULTS: Scintigraphic and ultrasound 50% emptying
      times (T50s) were comparable and longer (p < 0.001) for dextrose than soup mean
      (SEM) (dextrose 107 (16) min v 108 (18) min, soup 24 (4) min v 23 (5) min). There
      were close correlations between scintigraphic and ultrasound T50s (dextrose r =
      0.94, p < 0.005, soup r = 0.97, p < 0.001) and between the time at which the
      distal stomach content decreased from its maximum value by 50% (measured
      scintigraphically) and the ultrasound T50 (dextrose r = 0.95, p < 0.005, soup r =
      0.99, p < 0.0001). In contrast, there was no significant relation between the
      distal stomach content when expressed as a percentage of the maximum content in
      the total stomach and the ultrasound T50. After dextrose, fullness was related (r
      = 0.92, p < 0.01) to the postprandial increase in antral area measured by
      ultrasound. CONCLUSIONS: Ultrasound measurements of gastric emptying are: (a) of
      comparable sensitivity to scintigraphy in quantifying emptying of both low and
      high nutrient liquids (b) correlate with postprandial satiation, suggesting that
      the latter may be mediated by antral distension.

PMID- 8984017
TI  - Non-ulcer dyspepsia and peptic ulcer: the distribution in a population and their
      relation to risk factors.
AB  - BACKGROUND: The aetiology of non-ulcer dyspepsia and a possible connection to
      peptic ulcer disease is debated. This paper discusses this problem in a
      population based study. AIMS: The relation between non-ulcer dyspepsia and peptic
      ulcer disease was explored by the distribution in the general population and
      their associations to demographic, lifestyle, and psychological factors. METHODS:
      All inhabitants of a community aged 20-69 years received a questionnaire
      concerning abdominal complaints, health, lifestyle, diet, and social conditions.
      Reports on peptic ulcer were verified with medical records. Dyspeptic subjects
      and matched healthy, non-dyspeptic controls were endoscoped in a blinded
      procedure. SUBJECTS: Of 2027 persons invited, 1802 (88.9%) returned the
      questionnaire from which dyspeptic subjects and controls were identified. Of 782
      subjects invited to endoscopy, 309 dyspeptic and 310 control subjects (79.2%),
      participated. RESULTS: Men reported dyspepsia (30.4%) and peptic ulcer (8.7%)
      more often than women (24.1% and 5.2%, respectively). Non-ulcer dyspepsia was
      frequent (between 10.6% and 17.2%) in both sexes and age groups up to 60 years,
      with a lower frequency in both men and women above this age (3.0% and 6.8%). Non
      ulcer dyspepsia was associated with having a family history of dyspepsia and of
      peptic ulcer and the use of tranquillisers. Nearly one third of dyspeptic persons
      above the age of 40 years had peptic ulcer, but peptic ulcer prevalence was low
      under this age. Peptic ulcer was associated with a family history of peptic
      ulcer, smoking, and daily life stress, and also with poor living conditions
      during childhood, frequent recurrence of herpes labialis, conditions that were
      associated with Helicobacter pylori infection. CONCLUSIONS: Non-ulcer dyspepsia
      and peptic ulcer have different patterns of relations to lifestyle, social, and
      psychological factors. The results perhaps support the hypothesis of peptic ulcer
      being an infectious disease in contrast with non-ulcer dyspepsia.

PMID- 8984018
TI  - Sulphydryl blocker induced gastric damage is ameliorated by scavenging of free
      radicals.
AB  - BACKGROUND: Sulphydryl compounds and nitric oxide are essential in maintaining
      gastric mucosal integrity. AIMS: To characterise the gastric damage induced by a
      sulphydryl blocker, to evaluate the role of nitric oxide in its pathogenesis, and
      to reveal its possible prevention by scavenging of free radicals. METHODS:
      Gastritis was induced in rats by addition of iodoacetamide (0.1%) to the drinking
      water, with and without daily intragastric administration of TEMPOL. After death,
      the stomach was resected, washed, lesion area assessed, and mucosal inflammatory
      mediators, myeloperoxidase and nitric oxide synthase activities were determined.
      RESULTS: Administration of iodoacetamide induced gastric mucosal erosions present
      for up to two weeks. Myeloperoxidase activity was increased for up to seven days
      and nitric oxide synthase activity was significantly decreased for up to 14 days.
      Treatment for seven days with the free radical scavenger, TEMPOL, decreased by
      68% the damage induced by iodoacetamide. CONCLUSIONS: Gastric damage induced by
      iodoacetamide, a sulphydryl alkylator, accompanied by inhibition of nitric oxide
      synthase activity shows the important contribution of sulphydryl compounds and
      nitric oxide to the maintenance of gastric mucosal integrity. Nitric oxide
      donation and scavenging of free radicals may be a novel approach to prevent
      gastric damage.

PMID- 8984019
TI  - Effect of capsaicin and cimetidine on the healing of acetic acid induced gastric
      ulceration in the rat.
AB  - BACKGROUND: Capsaicin protects the gastric mucosa against experimental injury
      while capsaicin desensitisation reduces the rate of gastric ulcer healing. The
      effect of exogenous capsaicin on gastric ulcer healing has not to date been
      reported. AIM/METHOD: To investigate the effect of capsaicin, cimetidine, and in
      combination, given intragastrically in the healing of acetic acid induced chronic
      gastric ulcer in the rat. Treatment started immediately after ulcer induction.
      RESULTS: At the end of one week, capsaicin, cimetidine, and in combination
      increased ulcer healing but the effect of combined treatment was less than that
      of capsaicin alone. In an in vivo gastric chamber preparation, capsaicin
      increased, while cimetidine decreased, gastric mucosal blood flow measured by
      laser Doppler flowmetry. A dose response effect in reduction of gastric mucosal
      blood flow could be demonstrated for cimetidine. The gastric hyperaemic effect of
      capsaicin was blunted by prior administration of cimetidine. In contrast,
      capsaicin had no effect on gastric acid secretion and its addition to cimetidine
      did not affect the acid suppressant effect of the latter. CONCLUSIONS: Capsaicin
      promotes the healing of acetic acid induced gastric ulcer, probably by its
      gastric hyperaemic effect. Although cimetidine also promotes ulcer healing due to
      its inhibitory effect on acid secretion it may have an antagonistic effect on the
      gastric ulcer healing effect of capsaicin by virtue of inhibition of gastric
      hyperaemia.

PMID- 8984020
TI  - B-cell clonality and infection with Helicobacter pylori: implications for
      development of gastric lymphoma.
AB  - BACKGROUND: Although Helicobacter pylori has been implicated in the pathogenesis
      of gastric mucosa associated lymphoid tissue (MALT) and MALT lymphoma, it is not
      known how it may trigger these lesions and whether there is an identifiable pre
      neoplastic stage. AIMS: To investigate the relation between MALT, H pylori
      infection, and B-cell clonality (a potential marker of pre-neoplastic lesions).
      PATIENTS: 141 subjects with simple dyspepsia. METHODS: Gastric biopsy specimens
      from all patients were examined for MALT and H pylori. Of these, 25 consecutive
      MALT positive specimens were scored for features of MALT lymphoma and VDJ
      clonality studied by polymerase chain reaction. RESULTS: Overall, prevalence was
      62% for H pylori and 46% for MALT. VDJ clonality was frequent in the sub-group
      studied (nine of 25), mostly associated with lymphoid follicles (eight of nine or
      89%), and with a high scoring for MALT lymphoma. VDJ clonality was equally
      frequent in patients with and without H pylori (seven of 20 and two of five or
      35% and 40% respectively). CONCLUSIONS: B-cell clonality is unexpectedly common
      in subjects with simple dyspepsia and MALT raising clinical management questions.
      These findings also suggest that the cascade MALT formation--B-cell clonality-
      MALT lymphoma may not be uniquely associated with H pylori infection.

PMID- 8984021
TI  - Association of cytotoxin production and neutrophil activation by strains of
      Helicobacter pylori isolated from patients with peptic ulceration and chronic
      gastritis.
AB  - BACKGROUND: Helicobacter pylori is associated with neutrophil infiltration within
      the gastroduodenal mucosa. Neutrophil activation provides a major source of
      oxygen free radicals, which have been implicated in the pathogenesis of peptic
      ulceration. AIM: To investigate if cytotoxin producing strains of H pylori are
      associated with the generation of oxidative burst in polymorphonuclear
      neutrophils (PMNs). PATIENTS: 76 patients undergoing endoscopy of whom 45 had
      peptic ulcer and 31 chronic gastritis only were studied. METHODS: Strains of H
      pylori were cultured in Brucella broth. After 48 hours, bacteria were harvested
      by centrifugation and a bacterial suspension prepared as a stimulus for PMN
      oxidative burst using chemiluminescence. PMNs were prepared from health blood
      donors. To test the ability of strains to produce cytotoxin, culture supernatants
      of each were concentrated by polyethylene glycol and tested on cultured Vero
      cells for intracellular vacuolation. RESULTS: 30 of 45 (66.7%) peptic ulcer
      patients induced cell vacuolation versus nine of 31 (29%) strains from patients
      with chronic gastritis only (p < 0.01). Cytotoxin positive strains of H pylori
      regardless of the presence or absence of peptic ulcer displayed an increased
      induction of respiratory burst in PMNs compared with toxin negative strains from
      patients with chronic gastritis only (p < 0.05). Among the toxin negative
      strains, those from patients with peptic ulcer did not show a significant
      increase of the oxidative burst than those from patients without peptic ulcer
      (NS). CONCLUSION: Toxinogenicity of strains of H pylori seems to be correlated
      with neutrophil respiratory burst and peptic ulceration. The ability of some
      strains of H pylori to produce cytotoxin and to induce the oxidative burst in
      neutrophils may be important in the pathogenesis of peptic ulcer disease.

PMID- 8984022
TI  - Changes in the enterocyte cytoskeleton in newborn rats exposed to ethanol in
      utero.
AB  - BACKGROUND: Cytoskeletal changes after longterm exposure to ethanol have been
      described in a number of cell types in adult rat and humans. These changes can
      play a key part in the impairment of nutrient assimilation and postnatal growth
      retardation after prenatal damage of the intestinal epithelium produced by
      ethanol intake. AIMS: To determine, in the newborn rat, which cytoskeletal
      proteins are affected by longterm ethanol exposure in utero and to what extent.
      ANIMALS: The offspring of two experimental groups of female Wistar rats: ethanol
      treated group receiving up to 25% (w/v) of ethanol in the drinking fluid and
      control group receiving water as drinking fluid. METHODS: Single and double
      electron microscopy immunolocalisation and label density estimation of
      cytoskeletal proteins on sections of proximal small intestine incubated with
      monoclonal antibodies against actin, alpha-tubulin, cytokeratin (polypeptides 1,
      5, 6, 7, 8, 10, 11, and 18), and with a polyclonal antibody anti-beta 1,4
      galactosyl transferase as trans golgi (TG) or trans golgi network (TGN) marker,
      or both. SDS-PAGE technique was also performed on cytoskeletal enriched fractions
      from small intestine. Western blotting analysis was carried out by incubation
      with the same antibodies used for immunolocalisation. RESULTS: Intestinal
      epithelium of newborn rats from the ethanol treated group showed an
      overexpression of cytoskeletal polypeptides ranging from 39 to 54 kDa, affecting
      actin and some cytokeratins, but not tubulin. Furthermore, a cytokeratin related
      polypeptide of 28-29 kDa was identified together with an increase in free
      ubiquitin in the same group. It was noteworthy that actin and cytokeratin were
      abnormally located in the TG or the TGN, or both. CONCLUSIONS: Longterm exposure
      to ethanol in utero causes severe dysfunction in the cytoskeleton of the
      developing intestinal epithelium. Actin and cytokeratins, which are involved in
      cytoskeleton anchoring to plasma membrane and cell adhesion, are particularly
      affected, showing overexpression, impaired proteolysis, and mislocalisation.

PMID- 8984023
TI  - Developmental differences in the expression of the cholera toxin sensitive
      subunit (Gs alpha) of adenylate cyclase in the rat small intestine.
AB  - BACKGROUND: The stimulatory guanosine triphosphate (GTP) binding protein alpha
      subunit (Gs alpha) of adenylate cyclase is the target protein for cholera toxin.
      AIMS/METHODS: The expression of this signal transducer was analysed in the small
      intestine of developing rats by RNA transfer (northern blot) analysis by
      immunoblotting, and by ADP-ribosylation of membrane proteins. RESULTS: Intestinal
      Gs alpha mRNA (about 1.9 kb) was increased in the neonate compared with the adult
      rat. Two isoforms of Gs alpha proteins, a 45,000 and a 52,000 form, were
      expressed in the small intestinal epithelial cell and both were ADP-ribosylated
      by cholera toxin. A significant increase in the larger isoform (52,000) and in
      its ribosylation was noted in the 2 week old suckling compared with post-weaned
      older animals. The protein content or ribosylation of the smaller form (45,000)
      did not significantly change with age. CONCLUSION: These data show that a
      developmental decline of intestinal Gs alpha expression seems to be, in part,
      regulated at the mRNA level. An increased Gs alpha expression in the immature
      intestine may help to explain a previously reported, dose dependent increased
      adenylate cyclase response and an increase in fluid secretion to cholera toxin in
      neonates compared with adults.

PMID- 8984024
TI  - Effect of intestinal resection on human small bowel motility.
AB  - BACKGROUND: Few data are available on adaptive changes of human small bowel
      motility after intestinal resection. AIM: To characterise jejunal motility after
      extensive and limited distal intestinal resection. METHODS: Seven patients with a
      short bowel syndrome after total ileal and partial jejunal resection (residual
      jejunal segments between 60 and 100 cm) and six patients with limited distal
      ileal resection (resected segment between 30 and 70 cm) underwent ambulatory 24
      hour jejunal manometry 15 (6-24) months after the operation. Normal values were
      obtained from 50 healthy subjects. Fasting motility and the motor response to a
      600 kcal solid meal were analysed visually and by a computer program. RESULTS:
      Limited ileal resection did not result in changed jejunal motility. After
      extensive distal resection, patients had a significantly shorter migrating motor
      complex (MMC) cycle and a significantly shorter duration of the postprandial
      motor response compared with controls (p < 0.005). Intestinal resection had no
      influence on jejunal contraction frequency and amplitude and did not lead to any
      abnormal motor pattern. CONCLUSION: Extensive distal resection of the small
      intestine produces distinct abnormalities of fasting and postprandial motility in
      the intestinal remnant. The shortening of digestive motility and the increased
      frequency of MMC cycling could contribute to malabsorption and diarrhoea in the
      short bowel syndrome.

PMID- 8984025
TI  - Assessing the site of increased intestinal permeability in coeliac and
      inflammatory bowel disease.
AB  - BACKGROUND: The precise site of intestinal permeability changes in patients with
      coeliac and inflammatory bowel disease is unknown. AIMS: To design a non-invasive
      technique for the localisation of altered gastrointestinal permeability to
      51chromium labelled EDTA (51CrEDTA). The method depends on comparing and defining
      concentration/time profiles in serum of a series of simultaneously ingested
      indicators with a well defined absorption site (3-0-methyl-D-glucose (jejunal
      indicator), 57cobalt labelled vitamin B12 (ileal indicator), and sulphasalazine
      (caecal-colonic indicator)) in relation to simultaneously ingested 51CrEDTA.
      SUBJECTS: Five normal controls, six patients with untreated coeliac disease, five
      with Crohn's ileitis, and five with pan-ulcerative colitis underwent study, which
      entailed the simultaneous ingestion of the above four test substances followed,
      during the next 24 hours, by timed serial collection of urine and serum for
      marker analysis. RESULTS: Urinary excretion of 51CrEDTA was significantly
      increased in all patient groups. Analysis of serum appearances and profiles of
      the markers suggested that the increased intestinal permeation of 51CrEDTA took
      place in the diseased jejunum in patients with coeliac disease, predominantly in
      the ileum in Crohn's disease and in the colon in the patients with pan-ulcerative
      colitis. CONCLUSION: A new non-invasive technique has been assessed that permits
      the localisation of the site of permeability changes with the gastrointestinal
      tract.

PMID- 8984026
TI  - Relations between transit time, fermentation products, and hydrogen consuming
      flora in healthy humans.
AB  - BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming
      flora and certain indices of colonic bacterial fermentation. METHODS: Eight
      healthy volunteers (four methane excretors and four non-methane excretors) were
      studied for three, three week periods during which they received a controlled
      diet alone (control period), and then the same diet with cisapride or loperamide.
      At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose
      breath test was performed, and stools were analysed. RESULTS: In the control
      period, transit time was inversely related to faecal weight, sulphate reducing
      bacteria counts, concentrations of total short chain fatty acids (SCFAs),
      propionic and butyric acids, and H2 excreted in breath after lactulose ingestion.
      Conversely, transit time was positively related to faecal pH and tended to be
      related to methanogen counts. Methanogenic bacteria counts were inversely related
      to those of sulphate reducing bacteria and methane excretors had slower MTT and
      lower sulphate reducing bacteria counts than non-methane excretors. Compared with
      the control period, MTT was significantly shortened (p < 0.05) by cisapride and
      prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12)
      hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride
      reduced transit time was associated with (a) a significant rise in faecal weight,
      sulphate reducing bacteria, concentrations of total SCFAs, and propionic and
      butyric acids and breath H2 as well as (b) a significant fall in faecal pH and
      breath CH4 excretion, and (c) a non-significant decrease in the counts of
      methanogenic bacteria. Reverse relations were roughly the same during the
      loperamide period including a significant rise in the counts of methanogenic
      bacteria and a significant fall in those of sulphate reducing bacteria.
      CONCLUSIONS: Transit time differences between healthy volunteers are associated
      with differences in H2 consuming flora and certain indices of colonic
      fermentation. Considering the effects of some fermentation products on intestinal
      morphology and function, these variations may be relevant to the pathogenesis of
      colorectal diseases.

PMID- 8984028
TI  - Mucosal enzyme activity for butyrate oxidation; no defect in patients with
      ulcerative colitis.
AB  - BACKGROUND: Butyrate is an important energy source for the colon and its
      metabolism has been reported to be defective in ulcerative colitis. One mechanism
      for defective butyrate metabolism in patients with ulcerative colitis could be an
      enzyme deficiency in the beta-oxidation pathway of butyrate. AIMS: This study was
      undertaken to measure the activity of each enzyme involved in the beta-oxidation
      pathway of butyrate in colonic epithelium. PATIENTS: Patients with ulcerative
      colitis (n = 33), Crohn's colitis (n = 10), and control subjects with colorectal
      cancer or diverticular disease (n = 73) were studied. METHODS: Analysis was
      carried out using fluorometric and spectrophotometric techniques on homogenised
      epithelial biopsy specimens. RESULTS: Significantly increased butyryl CoA
      dehydrogenase activity was found in mucosa from patients with ulcerative colitis
      (33.2 (28.3, 38.1) mumol/g wet weight/min:mean (95% CI)) compared with activity
      in mucosa from control patients (24.3 (20.9, 27.7) mumol/g wet weight/min:mean
      (95% CI)) p < 0.02. No significant increase in activity of the enzymes butyryl
      CoA synthetase, crotonase or hydroxybutyryl-CoA dehydrogenase was found in
      patients with ulcerative colitis. In contrast the mucosal thiolase activity was
      significantly lower in those patients with quiescent colitis (3.21 (2.61, 3.81)
      mumol/g wet weight/min:mean (95% CI)) when compared with control mucosa (5.69
      (5.09, 6.29) mumol/g wet weight/min:mean (95% CI)) p < 0.001. However, mucosal
      thiolase activity increases with the age of the donor patient and differences in
      the age range of the patient groups probably account for this finding.
      CONCLUSIONS: This study shows no substantial deficiency of enzyme activity in the
      beta-oxidation pathway of butyrate in the mucosa of patients with ulcerative
      colitis in histological remission.

PMID- 8984027
TI  - Effect of L-glutamine and n-butyrate on the restitution of rat colonic mucosa
      after acid induced injury.
AB  - BACKGROUND: L-glutamine and n-butyrate are important nutrients for colonocytes
      affecting both their structure and function. The effect of these epithelial
      substrates on resealing of rat distal colon after acid induced injury was
      studied. METHODS: Isolated colonic mucosa of 32 rats was mounted in Ussing
      chambers and exposed to Krebs-Ringer solution for four hours. Epithelial injury
      was induced by short-term exposure to luminal hydrochloric acid and resealing was
      studied with or without added glutamine or butyrate. RESULTS: Glutamine (luminal
      and serosal) reduced tissue conductance, mannitol and lactulose permeability, and
      permeation of enteropathogenic Escherichia coli. Glutamine (serosal) diminished
      conductance and mannitol permeability. Both interventions stimulated
      bromodeoxyuridine incorporation in nuclei of colonocytes. Luminal butyrate had no
      measurable effect on these parameters. CONCLUSIONS: These data suggest that L
      glutamine stimulates repair mechanisms of rat colonic mucosa after acid injury.
      This effect on the gut barrier is associated with a stimulation of crypt cell
      proliferation. The addition of glutamine to parenteral solutions may be
      beneficial for patients under intensive care whose intestinal barrier is weakened
      in the course of sepsis and trauma.

PMID- 8984029
TI  - Antineutrophil cytoplasmic antibodies in sera from colectomised ulcerative
      colitis patients and its relation to the presence of pouchitis.
AB  - BACKGROUND: Few studies have evaluated the influence of colectomy on
      antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis (UC).
      In small series of patients it has been suggested that ANCA positivity in UC
      might be predictive for development of pouchitis after colectomy. AIMS: To assess
      the prevalence of ANCA in UC patients treated by colectomy and a Brooke's
      ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA), and the relation
      between the presence of ANCA, the type of surgery, and the presence of pouchitis.
      SUBJECTS: 63 UC patients treated by colectomy (32 with UC-BI and 31 with UC
      IPAA), 54 UC, and 24 controls. METHODS: Samples were obtained at least two years
      after colectomy. ANCA were detected by indirect immunofluorescent assay. RESULTS:
      There were no differences between patients with (36.3%) or without pouchitis
      (35.0%) and between patients with UC (55%), UC-BI (40.6%), and UC-IPAA (35.4%).
      However, ANCA prevalence significantly decreases in the whole group of operated
      patients (38.0%) compared with non-operated UC (p = 0.044). CONCLUSIONS: The
      prevalence of ANCA in operated patients was significantly lower than in non
      operated UC, suggesting that it might be related either to the presence of
      inflamed or diseased tissue. ANCA persistence is not related to the surgical
      procedure and it should not be used as a marker for predicting the development of
      pouchitis.

PMID- 8984030
TI  - Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor,
      accelerates healing in a rat model of chronic colitis.
AB  - BACKGROUND: 5-Lipoxygenase products play a part in inflammatory response. AIMS:
      The effect of intracolonic administration of zileuton (a 5-lipoxygenase
      inhibitor) on colonic damage and eicosanoid local release was assessed in a rat
      model of colitis. METHODS: Ninety rats with trinitrobenzenesulphonic acid induced
      colitis were randomised to receive placebo, 5-aminosalicylic acid (50 mg/kg), or
      zileuton (50 mg/kg) intracolonically for four weeks. Local eicosanoid release was
      monitored by intracolonic dialysis throughout the study. The colon was removed
      for macroscopic and histological assessment at weeks 1, 2, and 4 after colitis
      induction in 10 rats of each group. RESULTS: Zileuton significantly reduced
      macroscopic damage score after four weeks of treatment in comparison with the
      other two groups (p = 0.034). In addition, zileuton administration significantly
      increased the intracolonic release of both thromboxane B2 at week 1 (p = 0.05)
      and prostaglandin E2 at weeks 2 and 4 (p < 0.05). Zileuton and 5-aminosalicylic
      acid decreased leukotriene B4 release by 90% at day 3. CONCLUSIONS: Intracolonic
      zileuton, compared with 5-aminosalicylic acid and placebo, seems to improve the
      course of the disease in a model of chronic colitis. This effect may be related
      to an increased and maintained production of prostaglandin E2 together with
      inhibition of leukotriene B4 synthesis.

PMID- 8984031
TI  - Predicting outcome in severe ulcerative colitis.
AB  - BACKGROUND: Simple criteria are needed to predict which patients with severe
      ulcerative colitis will respond poorly to intensive medical treatment and require
      colectomy. AIMS: To find out if the early pattern of change in inflammatory
      markers or other variables could predict the need for surgery and to evaluate the
      outcome of medical treatment during one year follow up. PATIENTS: 51 consecutive
      episodes of severe colitis (Truelove and Witts criteria) affecting 49 patients
      admitted to John Radcliffe Hospital, Oxford. METHODS: Prospective study
      monitoring 36 clinical, laboratory, and radiographic variables. All episodes
      treated with intravenous and rectal hydrocortisone and 14 of 51 with
      cyclosporine. RESULTS: Complete response in 21 episodes (< or = 3 stools on day
      7, without visible blood), incomplete response in 15 (> 3 stools or visible blood
      on day 7, but no colectomy), and colectomy on that admission in 15. During the
      first five days, stool frequency and C reactive protein (CRP) distinguished
      between outcomes (p < 0.00625, corrected for multiple comparisons) irrespective
      of whether patients or the number of episodes were analysed. It could be
      predicted on day 3, that 85% of patients with more than eight stools on that day,
      or a stool frequency between three and eight together with a CRP > 45 mg/l, would
      require colectomy. For patients given cyclosporine, four of 14 avoided colectomy
      but two continued to have symptoms. After admission, complete responders remained
      in remission for a median nine months and had a 5% chance of colectomy.
      Incomplete responders had a 60% chance of continuous symptoms and 40% chance of
      colectomy. CONCLUSIONS: After three days intensive treatment, patients with
      frequent stools (> 8/day), or raised CRP (> 45 mg/l) need to be identified, as
      most will require colectomy on that admission. The role of cyclosporine for
      treating severe colitis has yet to be defined. After seven days' treatment,
      patients with > 3 stools/day of visible blood have a 60% chance of continuous
      symptoms and 40% chance of colectomy in the following months.

PMID- 8984032
TI  - Role of interleukin 8 on leucocyte-endothelial cell adhesion in intestinal
      inflammation.
AB  - BACKGROUND: An important action of interleukin 8 (IL8) is stimulation of
      granulocytes. The object of this study was to assess the contribution of IL8 to
      the leucocyte-endothelial cell interactions associated with intestinal
      inflammation in the rat. METHODS: Two indomethacin injections (48 and 24 hours
      prior to the experiments) induced a longlasting ileitis in rats. The number of
      adherent and emigrated leucocytes, leucocyte rolling velocity, and shear rate
      were monitored in normal and inflamed mesenteric postcapillary venules. Some
      animals received a monoclonal antibody (MAb) against IL8 or CD11b/CD18 at 24 and
      12 hours prior to the experiment. RESULTS: Indomethacin elicited a seven-fold
      increase in leucocyte adherence and a 5.4-fold increase in leucocyte emigration,
      while leucocyte rolling velocity was reduced by nearly 80%. The indomethacin
      induced increases in leucocyte adherence and emigration were significantly
      reduced (by 57% and 67%, respectively) while leucocyte rolling velocity was
      increased (to 63% of control) by the IL8-specific MAb. The level of inhibition
      seen with the IL8 MAb was similar to that associated with administration of a MAb
      directed against the leucocyte adhesion molecule CD11b/CD18. CONCLUSIONS: IL8
      contributes to the leucocyte-endothelial cell interactions elicited in mesenteric
      venules by indomethacin.

PMID- 8984033
TI  - Attenuated GLP-1 secretion in obesity: cause or consequence?
AB  - BACKGROUND: Hypersecretion of insulinotropic factors such as glucose dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide-1(7-36)amide (GLP-1)
      have been postulated to account for the hyperinsulinaemia of obesity. AIMS: To
      examine the role of GLP-1 and GIP in obese women and matched controls. SUBJECTS:
      Six lean and six obese women subjects matched for age. METHODS: The gut hormone,
      plasma glucose, and serum triglyceride responses were studied over 180 minutes
      after oral carbohydrate and fat meals. Heparin (10,000 units) was given
      intravenously at 120 minutes. RESULTS: There was pronounced attenuation of plasma
      GLP-1 secretion to oral carbohydrate in the obese compared with lean subjects but
      no such difference in response to oral fat load. There were no differences in the
      plasma GIP responses to carbohydrate or fat feeding. There was an apparent fall
      in plasma GLP-1 values in all subjects after administration of heparin.
      CONCLUSION: Postprandial GLP-1 secretion in response to oral carbohydrate is
      considerably attenuated in obese subjects. The cause of this attenuation of GLP-1
      secretion is not known although we suggest that both this fall and the overall
      reduction in GLP-1 values in obese subjects may be related to an increase in
      plasma non-esterified fatty acids.

PMID- 8984034
TI  - Nutrients and cyclical interdigestive pancreatic enzyme secretion in humans.
AB  - BACKGROUND AND AIMS: It is hypothesised that nutrients increase pancreatic enzyme
      secretion by converting cyclical interdigestive secretion to a non-cyclical
      pattern. This study tested the hypotheses that nutrients do not interrupt cycles
      and determined the relation of nutrients, calories, and osmotic load to the rate
      of pancreatic secretion. METHODS: Twenty six healthy persons were intubated with
      oroduodenal and orogastric tubes. Each had one of four different solutions
      containing 12 to 36% of calories as protein, 24 to 48% as fat, and 40 to 64% as
      carbohydrate infused into the duodenum at 40, 90, or 160 kcal/h for 300 minutes.
      Nine g/l sodium chloride (290 mOsm) was added to 16 infusates; osmolality of the
      other 10 infusates was 24 to 98 mOsm. Pancreatic enzyme outputs were measured
      every 15 minutes and peaks of enzyme secretion were identified. RESULTS: The
      number of enzyme peaks was similar for the different infusates and the proportion
      of nutrients in the infusates did not affect secretion of individual enzymes. The
      nadir, but not the peak of the cycles of enzyme outputs correlated with
      increasing the caloric load (r = 0.55, p < 0.003 for nadir:peak ratio).
      Increasing osmolality did not affect cycling but reduced (p < 0.001) enzyme
      output. CONCLUSION: Nutrients entering the duodenum do not abolish cycles of
      enzyme secretion; instead they modulate cycles by increasing the nadir. Forty and
      90 kcal infusions submaximally stimulate pancreatic secretion and might be used
      in patients with pancreatitis without producing pain; adding sodium chloride to
      solutions should increase this effect.

PMID- 8984035
TI  - Biliary decompression promotes Kupffer cell recovery in obstructive jaundice.
AB  - BACKGROUND: Jaundiced patients undergoing surgical procedures have an increased
      risk of Gram negative sepsis with potential morbidity and mortality. Depressed
      Kupffer cell clearance capacity (KCCC) predisposes jaundiced patients to
      endotoxaemia and its sequelae. Biliary decompression remains the main therapeutic
      strategy in obstructive jaundice. AIMS: This study investigates the efficacy of
      internal (ID) and external biliary drainage (ED) on KCCC in an experimental model
      of extrahepatic biliary obstruction. METHODS: Adult male Wistar rats (250-300 g)
      were assigned to one of six groups: sham operated, where the bile duct was
      mobilised but not divided; bile duct ligation (BDL) for three weeks, and sham
      operated or BDL for three weeks followed by a second laparotomy and further 21
      days of ID or ED, by way of choledochoduodenostomy or choledochovesical fistula
      respectively. KCCC was measured using an isolated hepatic perfusion technique
      with FITC labelled latex particles (0.75 mu) as the test probe. Plasma was
      assayed for bilirubin, endotoxin, and anticore glycolipid antibody (ACGA)
      concentrations. RESULTS: Jaundiced rats had reduced KCCC (p < 0.001), increased
      concentrations of ACGA (p < 0.001), and endotoxin (p < 0.001) compared with
      controls. Biliary drainage for three weeks produced a recovery in KCCC and
      normalisation of endotoxin and ACGA concentrations, however, external drainage
      was less effective than ID (p < 0.01). CONCLUSIONS: These data support the
      hypothesis that endotoxaemia and its mediated effects are integral in the
      pathophysiology of jaundice. Furthermore, a short period of internal biliary
      drainage is a useful therapeutic strategy in restoring Kupffer cell function and
      negating systemic endotoxaemia and consequent complications in biliary
      obstruction.

PMID- 8984036
TI  - Bleeding anorectal varices: successful treatment with transjugular intrahepatic
      portosystemic shunting (TIPS).
AB  - A patient with severe recurrent rectal bleeding from anorectal varices due to
      portal hypertension because of hepatitis C virus related liver cirrhosis is
      presented. As illustrated by the report, it is essential to differentiate
      bleeding anorectal varices from bleeding haemorrhoids because treatment is
      different. In our patient, implantation of a transjugular intrahepatic
      portosystemic shunt (TIPS) led to an impressive regression of the anorectal
      varices, which could be demonstrated by sigmoidoscopy, endosonography, and
      magnetic resonance imaging. Recurrent rectal bleeding in a patient with portal
      hypertension should alert the physician to consider anorectal varices. Endoscopic
      ultra-sound and magnetic resonance imaging are new and non-invasive modalities
      for diagnosis and post-treatment control.

PMID- 8984037
TI  - Percutaneous aspiration in the treatment of hydatid liver cysts.

PMID- 8984038
TI  - Ulcerative colitis and renal cell carcinoma.

PMID- 8984039
TI  - Hepatocellular carcinoma and african iron overload.

PMID- 8984040
TI  - Analysis of biological variables in Crohn's disease.

PMID- 8984041
TI  - Preventing malnutrition: the critical period is 6 months to 2 years.

PMID- 8984042
TI  - Treatment of aplastic anemia in children with high dose methyl prednisolone.
AB  - Severe aplastic anemia (SAA) in children has been previously treated with high
      dose methyl prednisolone (HDMP) with favorable results. We reviewed our
      experience with intravenous HDMP. Seven children with a diagnosis of SAA
      confirmed on bone marrow biopsy were treated with 300 mg/kg total dose of
      intravenous HDMP over a 4 week period. Patients were closely monitored for
      response and side effects. HDMP was well tolerated except for hyperglycemia in
      one case. Six of the seven patients showed no response to HDMP. This observation
      is in stark contrast with previous trials on use of HDMP in SAA. It is concluded
      that HDMP should be reserved only for patients with milder bone marrow
      hypoplasia.

PMID- 8984043
TI  - Clinical and biochemical studies in homocystinuria.
AB  - Homocystinuria was diagnosed in 15 (0.59%) cases on screening 2560 children for
      aminoacidopathies. The commonest presenting features were ectopia lentis (95%)
      and mental retardation (86%). Other features included, dental anomalies (40%),
      osteoporosis (40%), behavioral problems (33%) and arachnodactyly (13%). Diagnosis
      was confirmed by iodoplatinate staining of one dimensional paper chromatography
      of urine. All the 15 cases of homocystinuria were first treated with high dose
      oral pyridoxine. Only one case responded to pyridoxine therapy. All the other
      patients were started on a low methionine, High cysteine diet with folate
      supplementation. Only one patient showed a complete response to dietary therapy.
      Nonavailability and high cost of the commercially available methionine-free,
      cysteine-supplemented diet and late diagnosis were responsible for the poor
      response in the majority of our patients.

PMID- 8984044
TI  - Evaluation of immunogenicity and tolerance of single dose haemophilus influenzae
      type B (PRP-T) vaccine.
AB  - OBJECTIVE: Evaluation of immunogenicity and acceptability of PRP-T vaccine among
      the Indian children. DESIGN: Multicentric, open, parallel group, comparative
      study of Haemophilus influenzae type B vaccine, given as single (Group I) or
      associated (Group II) with DPT vaccine. SETTING: Five different vaccination
      clinics. SUBJECTS: 125 children between the age group of 18-24 months.
      PARAMETERS: Measurement of (i) pre and post vaccination antibody titres of
      Haemophilus influenze type B specific antibody; (ii) Adverse events; and (iii)
      Tolerance as graded by the physician. RESULTS: Prevaccination antibody levels
      were > 0.15 mcg/ml in 56.3% in Group I and 35.7% in Group II. Post-seroconversion
      was seen in 97% in Group II receiving single and all in Group II (P > 0.05). The
      vaccine was well tolerated. CONCLUSIONS: The probability of subclinical infection
      or cross immunity is high in India. ACTHIB vaccine has a good immunogenicity and
      tolerance and association with DPT does not modify the immunogenicity of ACTHIB
      vaccine.

PMID- 8984045
TI  - Association of gastroesophageal reflux (GER) with bronchial asthma.
AB  - Eighty children with bronchial asthma and ten control cases underwent
      radionuclide gastroesophagography for the detection of gastroesophageal reflux.
      Thirty nine per cent asthmatic children demonstrated esophageal reflux on
      scintiscanning. The ten control subjects had no reflux. The presence of reflux
      correlated strongly with the presence of nocturnal exacerbation of symptoms.
      Bronchodilator therapy did not affect the prevalence of GER in asthmatic
      children.

PMID- 8984046
TI  - Serum adenosine deaminase estimation in relation to BCG vaccination.
AB  - Serum adenosine deaminase (ADA) levels reflect activity of stimulated T
      lymphocytes and its levels are raised whenever cell mediated immunity is
      stimulated. One hundred term normal newborns were studied to evaluate effect of
      BCG vaccination on serum ADA levels. Serum ADA was measured at birth and 6 weeks
      after BCG vaccination. Only 67 subjects came for follow up after 6 weeks. The
      levels were 6.69 U/litre at birth and 13.83 U/litre after 6 weeks of vaccination
      showing a significant rise. It is concluded that serum ADA levels can be used as
      a measure of cell mediated immunity after BCG vaccination.

PMID- 8984047
TI  - Perinatal mortality--a hospital based study.
AB  - A total of 5082 consecutive deliveries in Medical College Hospital, Kottayam
      during the period August 1992 to July 1993 constituted the study. Perinatal
      mortality rate (PMR) was 38.5 per 1000 total births and autopsy rate was 72%.
      More than 85% of perinatal deaths occured in low birth weight and preterm babies.
      Perinatal hypoxia and congenital anomalies were the leading causes in late fetal
      deaths (LFD). The main causes of early neonatal deaths (END) were perinatal
      hypoxia, infections, congenital anomalies and hyaline membrane disease (HMD).

PMID- 8984048
TI  - Magnetic resonance angiography in Moyamoya disease.

PMID- 8984049
TI  - Albendazole therapy in liver hydatidosis.

PMID- 8984050
TI  - Terfenadine overdose induced polymorphous ventricular tachycardia.

PMID- 8984051
TI  - Mesenchymal hamartoma of liver.

PMID- 8984052
TI  - Syndromic and isolated cryptophthalmos.

PMID- 8984053
TI  - Aplasia cutis congenita with congenital contracture of knee.

PMID- 8984054
TI  - Antipyretics induced erythema multiforme.

PMID- 8984055
TI  - Diet in chronic renal failure.

PMID- 8984056
TI  - Cisapride.

PMID- 8984057
TI  - Enteric fever in young children.

PMID- 8984058
TI  - Adenovirus gastroenteritis.

PMID- 8984059
TI  - Breath holding spells in a neonate.

PMID- 8984060
TI  - Child labor: action is needed.

PMID- 8984061
TI  - Does BCG immunization prevent tuberculosis?

PMID- 8984062
TI  - Typhoid vaccine.

PMID- 8984063
TI  - Transfusion of child's own blood.

PMID- 8984064
TI  - Lactobacillus GG in acute diarrhea.

PMID- 8984065
TI  - The squash drinking syndrome.

PMID- 8984066
TI  - Seasonality of mortality in Sri Lanka: biometeorological considerations.
AB  - The seasonal variation of mortality in Sri Lanka was studied in relation to
      meteorological variables. Time series data of the total monthly number of deaths
      in men and women from 1976 to 1980 were analyzed by power spectrum analysis of
      the fast Fourier transformation method in the areas of Colombo (lowland area,
      altitude 7 m) and Nuwara-Eliya (highland area, altitude 1890 m), respectively. In
      the Colombo area, where the mean temperature was always high (mean, 27.5 degrees
      C), a seasonal variation in mortality of 6 months was validated by power spectrum
      analysis with peak times in June and November. These mortality peaks corresponded
      to those of the amounts of rainfall which also showed an identical predominant
      period of 6 months. In the Nuwara Eliya area, where the mean temperature was
      always low at about 15-16 degrees C, a seasonal variation of approximately 3
      months was found in addition to the 6 months' periodicity. The comparison of the
      power spectrum pattern of mortality with those of meteorological variables
      suggested that the amount of rainfall was associated with the seasonal variation
      of mortality in the Nuwara-Eliya area. In conclusion, the seasonality of
      mortality in Sri Lanka, a typical tropical zone country, was related to seasonal
      variation in the amount of rainfall, or a humidity factor, but not to mean
      temperature.

PMID- 8984067
TI  - From patient to pipette --and back again, an international symposium about
      clinical and research aspects of dermatology, Jerusalem, Israel, October 2-7,
      1994.

PMID- 8984068
TI  - Women in dermatology, joint meeting of the international society of dermatology
      and the dermatology and venereology society, Istanbul, Turkey,June 8th, 1995.

PMID- 8984069
TI  - Seoul International Dermatology Symposium, Seoul, Korea, May 11-14, 1995.

PMID- 8984070
TI  - Increased maternal age and perinatal mortality.

PMID- 8984071
TI  - Outrage at 'dying rooms' in Chinese orphanages.

PMID- 8984072
TI  - Patient treatment preference in metastatic prostate cancer.
AB  - 40 male patients with metastatic prostate cancer given a choice of medical
      castration with the LHRH Analogue Goserelin (Zoladex) or surgical castration
      chose medical treatment. During a 15 month follow up only one patient decided to
      have an orchidectomy and this was because of treatment expense.

PMID- 8984073
TI  - Improving procedures for recording suicide statistics.
AB  - OBJECTIVE: To explore the changing relationship between rates of suicide and
      undetermined death in Britain and Ireland. DESIGN: Longitudinal analysis of the
      official statistics relating to unnatural deaths in England and Wales and the
      Republic of Ireland between 1976 and 1992. MAIN OUTCOME MEASURES: Male and female
      rates of suicide and undetermined deaths for Ireland and England and Wales, age
      adjusted to the standard world population. Ratio of undetermined deaths to
      suicide. RESULTS: The official Irish male suicide rate is now much higher than
      that of England and Wales while the female rates are broadly similar. The rate of
      undetermined deaths has risen amongst English males and remained stable for
      females but has significantly fallen off among both Irish males and females. The
      proportion of deaths classified as 'undetermined' is now very much less in
      Ireland than in England and Wales. DISCUSSION: National plans for suicide
      prevention in either country cannot be properly audited unless improved
      procedures are put in place to increase the validity and reliability of the
      official suicide figures. Each country could beneficially learn from the other in
      this regard.

PMID- 8984074
TI  - Galactosaemia--a controversial disorder. Screening & outcome. Ireland 1972-1992.
AB  - We reviewed 20 years (from 1972 to 1992) of screening for galactosaemia in
      Ireland. We looked at a small group of 32 patients followed up in the same centre
      since diagnosis. 1.2 million babies have been screened with 55 cases of classical
      galactosaemia and 7 Duarte Variants being detected. The frequency is thus,
      1:23,000 and is increased among itinerants to 1:700. The mean age of diagnosis
      was 6.9 days with 41/62 cases symptomatic at the time. There were 9 deaths, 8 in
      the first 10 years, six of whom were itinerants. On follow up of the 32 children,
      who have attended Temple Street Hospital, 13/32 have no detectable complication.
      Nineteen show either one or a combination of cataracts, speech problems, tremors,
      abnormal FSH and or LH, delayed mental development and recurring infections. The
      screening test is the Bacterial Inhibition Assay with Beutler test, an original
      blood spot as confirmation in presumptive possible cases. The Beutler test is
      performed urgently in high risk situations. Five classical galactosaemics gave
      false negative results, 3 because of poor feeding, and two because of soya milk
      formulas. Screening prevented deaths as 7/84 siblings of our cases were
      unexpected infant deaths, all but one predating screening. Unexplained delay in
      screening undermines its effectiveness. Survival is enhanced by aggressive
      neonatal care. Symptoms are improved on commencing diet, with cataracts
      regressing. Complications did not correlate with the day of starting diet.
      Galactose-1-Phosphate and urinary galactitol levels did not correlate with
      complications, but slit lamp examination has proved a helpful index of adherence
      to diet. The mechanism of complications is unclear, and it is essential that
      current research should be aggressively pursued to explain mental deficiency in
      cases treated either pre-natally or early in post natal life.

PMID- 8984075
TI  - Smoking in Irish journals: a content analysis 1960-1994.
AB  - This study was carried out to quantify the published research on smoking in Irish
      medical journals, to ascertain the type of research carried out and to identify
      the authors of that research. Five Irish medical journals published between 1960
      94 were studied: The Irish Journal of Medical Science. The Journal of the Irish
      Medical Association/The Irish Medical Journal. The Journal of the Irish Colleges
      of Physicians and Surgeons and Forum. During the 35 years under study, 50 papers
      explicitly dealing, with smoking were published. Only two papers appeared in
      Forum. There was a decline in published papers in the eighties with a resurgence
      in the early nineties. Of the 50 papers a majority were observational and ten
      were editorials. Only one paper dealt with smoking cessation and one with
      preventive work. General practitioners were poorly represented as authors. One
      doctor (Prof. R. Mulcahy) published at least one paper on smoking in each
      quinquennium since 1960. This study underlines the relative insignificance of
      smoking as a topic for research in Ireland. A major sea change in attitude will
      be required if the government's targets for smoking cessation are to be realised,
      particularly if they are to be achieved by relying on the medical.

PMID- 8984076
TI  - Meningococcus: a menace in Cork?
AB  - A review of laboratory isolates and notifications of meningococcal disease in the
      Cork area was conducted for the period 1989-93. The study aimed to describe the
      epidemiology of meningococcal disease in the area. The incidence of meningococcal
      disease is high in the Cork area and has been increasing since 1991 with a peak
      incidence of laboratory confirmed cases of 6.5 per 100,000 in 1993. In the five
      year review period 113 notifications of meningococcal disease were identified of
      which 61 (54%) were laboratory confirmed and 52 (46%) were clinically diagnosed
      only. All laboratory confirmed cases had been notified to the local Director of
      Community Care/Medical Officer of Health. Group C organisms comprised two-thirds
      of isolates in 1992 and 1993. Comparison of regional and national incidence rates
      must be based on laboratory confirmed cases as the criteria for diagnosis and
      completeness of notifications may vary. A National Infectious Disease
      Surveillance Centre is vital for monitoring trends and for the coordinated
      development of a national policy on control and prevention of meningococcal
      disease.

PMID- 8984077
TI  - Orthopaedic complications following cardiac transplantation.
AB  - Cardiac transplantation has become the treatment of choice for end stage heart
      disease. In 1990 2,000 transplants were performed worldwide. Orthopaedic Surgeons
      will be asked with increasing frequency to evaluate and treat bone and soft
      tissue problems with these patients. Orthopaedic service at the Mater Hospital
      has been involved in the follow-up treatment of orthopaedic complications in 46
      transplant patients over a six year period. Thirty eight were male and eight were
      female. The ages were between 12 years and 65 years (mean 44.3). Nine (20%) of
      these patients developed thirteen orthopaedic complications: A vascular Necrosis
      of the hip (AVN) (4), Soft tissue infections (3), Osteoporosis (2), Stress
      Fractures (2), Osteomyelitis (1) and Ostomalacia (1). The mode of presentation,
      investigation and management of orthopaedic problems particular to these patients
      is described. Most patients who develop bony complications have had increased
      doses of steroids for episodes of rejection. This study highlights the special
      features of this patient population that require modification of the treatment
      approach such as the need to avoid the drug Erythromycin and the increased risk
      of AVN of the hip in patients who require high dose steroids.

PMID- 8984078
TI  - Blind faith? A cause of pre-operative eye infection.

PMID- 8984079
TI  - Suboptimal compliance with periconceptual folic acid in an Irish hospital
      population.
AB  - Awareness of and compliance with periconceptual folate was measured by
      questionnaire in our antenatal and infertility populations. Awareness was
      somewhat better in the private antenatal and infertility patients, but compliance
      was universally very poor. A substantial proportion of pregnancies were planned,
      and therefore there is potential for a much higher level of compliance.

PMID- 8984080
TI  - Which formula should be used in Ireland to estimate fetal weight?
AB  - In order to determine which formula most accurately predicts weight in Irish
      infants we performed a prospective study on 162 mothers within one week of
      delivery. Actual weights were compared with estimated weights derived from the
      formulae of Shepard; Hadlock; Birnholtz; Deter and Campbell. Overall the Deter
      formula gave the closest approximation of birth weight. All the formulae became
      increasingly inaccurate in the larger infants i.e. > 4 kg. However in infants of
      average weight the Campbell formula, which is based on a single measurement
      (A.C), is as good as any.

PMID- 8984081
TI  - Oropharyngeal dysphagia.

PMID- 8984082
TI  - Asthma and wheeze in schoolchildren.
AB  - In a questionnaire survey of 2813 children aged 4 to 19 years 11.9% reported
      asthma compared to 4.4% in 1983-4: a rise of 170% over 9 years. The asthma
      prevalence was 8.35% in girls and 14.8% in boys. The prevalence of wheeze in the
      past 12 months was 12% in girls and 18.9% in boys. The wheeze prevalence values
      for 9 year olds were similar to those found in a recent study in Galway. 40.8% of
      those reporting wheeze in the previous 12 months did not report asthma. This
      suggests under diagnosis, ineffective communication of the diagnosis to the
      parents or denial of the diagnosis. 79% of those with asthma reported wheeze and
      10.7% reported cough but no wheeze ('cough variant asthma'), emphasising the
      importance of cough as an indicator of asthma in these children.

PMID- 8984083
TI  - Calcium channel blockers in the management of hypertension.

PMID- 8984084
TI  - Impact of sumatriptan on workplace productivity, nonwork activities, and health
      related quality of life among hospital employees with migraine.
AB  - This prospective, open-label study evaluated the effects of subcutaneous
      sumatriptan versus usual therapy on workplace productivity, activity time outside
      of work, and health-related quality of life in 43 men or women who were hospital
      employees diagnosed with migraine according to international Headache Society
      criteria. Patients treated migraines with their usual therapy for 12 to 18 weeks
      followed by subcutaneous sumatriptan for 6 months. Health-related quality of life
      measurements obtained at baseline, after usual therapy, and after sumatriptan
      therapy included the Short Form-36 Health Survey and the Migraine-Specific
      Quality of Life Questionnaire. Patient daily diaries were used to capture data on
      migraine symptoms and on Lost Workplace Productivity and Non-workplace Activity
      Time. Traditional clinical efficacy measures were obtained to support the
      pharmacoeconomic data. Clinical data showed that the percentage of treated
      migraine days per patient on which the patient experienced relief (moderate or
      severe pain reduced to mild or none) was 75% with sumatriptan and 25% with usual
      therapy. The mean time to meaningful relief was 1.1 hours during the sumatriptan
      phase and 4.2 hours during the usual therapy phase. Lost Workplace Productivity
      and Nonworkplace Activity Time was 35% lower with sumatriptan therapy (1.5 hours)
      compared with usual therapy (2.3 hours). Time missed from work due to symptoms,
      time worked with symptoms, and time normal activities were carried on with
      symptoms were each lower during sumatriptan therapy compared with usual therapy.
      Scores on each of the three Migraine-Specific Quality of Life Questionnaire
      dimensions and on the Role-Emotional dimension of the Short Form-36 were
      significantly more favorable after sumatriptan than after usual therapy (P <
      0.05). These data demonstrate that treatment of migraines with sumatriptan for 6
      months following usual therapy for 12 to 18 weeks was associated with improvement
      in clinical efficacy, reduction in lost workplace productivity and nonworkplace
      activity time, and enhancement of key dimensions of health-related quality of
      life among employees of a large university hospital.

PMID- 8984085
TI  - Effectiveness of subcutaneous dihydroergotamine by home injection for migraine.
AB  - The effectiveness of dihydroergotamine administered by home subcutaneous
      injection by the patient or family for severe headache attacks was assessed
      retrospectively in 51 patients. Average follow-up was 21 weeks. Twenty-one
      patients had intermittent migraine attacks, 27 had transformed migraine with
      chronic daily headache, and 3 had chronic tension-type headache. Of the 51
      patients taught home injection, 35% had an excellent overall response, 18% had a
      good response, 12% had a poor response but continued to use dihydroergotamine,
      and 35% had discontinued dihydroergotamine use. Side effects were the main reason
      for stopping dihydroergotamine. These included nausea or vomiting or both, limb
      pain or numbness or both, chest or throat tightness or both, and soreness at the
      injection site. Thirty-three patients (65%) continued to use dihydroergotamine at
      the end of the follow-up period. In patients who previously required injections
      from medical personnel for headache crises and in whom home injection of
      dihydroergotamine was effective, a dramatic reduction occurred in hospital
      emergency room and physician office utilization. Dihydroergotamine use by home
      injection can be an effective treatment for a significant proportion of patients
      with severe migraine including patients with transformed migraine and medication
      overuse.

PMID- 8984086
TI  - Effectiveness of a physical therapy regimen in the treatment of tension-type
      headache.
AB  - Twenty patients with diagnosis of muscle contraction headache were treated for
      pain relief in a physical therapy clinic once a week for six visits. The previous
      3-week period of no treatment served as a control period during which patients
      recorded by diary their headache frequency, duration, and intensity using a
      numeric pain scale. Activity level, as measured by the Sickness Impact Profile,
      and verbal reports of headache frequency, duration, and intensity were recorded
      at four points during a 1-year period. Measurements were recorded at precontrol,
      pretreatment, posttreatment, and 12-month follow-up. Treatment included education
      for posture at home and work place, isotonic home exercise, massage, and
      stretching to the cervical spine muscles. Results indicated frequency of
      headaches and Sickness Impact Profile scores were significantly improved (P <
      0.001) over the course of treatment. These benefits were maintained after 12
      months.

PMID- 8984087
TI  - Intravenous magnesium sulfate rapidly alleviates headaches of various types.
AB  - BACKGROUND: Circumstantial evidence points to the possible role of magnesium
      deficiency in the pathogenesis of headaches and has raised questions about the
      clinical utility of magnesium as a therapeutic regimen in some headaches.
      METHODS: We evaluated the efficacy of intravenous infusion of 1 gram of magnesium
      sulfate (MgSO4) for the treatment of patients with headaches and attempted to
      correlate clinical responses to the basal serum ionized magnesium (IMg2+) level.
      We also determined if patients with certain headache types exhibit low serum
      IMg2+ as opposed to total serum magnesium. Using a case-control comparison at an
      outpatient headache clinic, a consecutive sample of patients presenting with a
      moderate or severe headache of any type were included in the study. Of the 40
      patients in the study (mean age 38.2 +/- 9.4 years; range 14 to 55; 11 men [39.2
      +/- 7.3 years] and 29 women [37.8 +/- 10.2 years]), 16 patients had migraines
      without aura, 9 patients had cluster headaches, 4 patients had chronic tension
      type headaches, and 11 had chronic migrainous headaches. Total serum magnesium
      was measured with atomic absorption spectroscopy and a Kodak Ektachem DT-60.
      Sensitive ion selective electrodes were utilized to measure serum IMg2+ and
      ionized calcium (ICa2+); ICa2+/IMg2+ ratios were calculated. RESULTS: Complete
      elimination of pain was observed in 80% of the patients within 15 minutes of
      infusion of MgSO4. No recurrence or worsening of pain was observed within 24
      hours in 56% of the patients. Patients treated with MgSO4 observed complete
      elimination of migraine-associated symptoms such as photophobia and phonophobia
      as well as nausea. Correlation was noted between immediate and 24-hour responses
      with the serum IMg2+ levels. Immediate pain relief was observed in 32 (80%) of 40
      patients (P < 0.001). In 18. of the 32 patients, pain relief persisted for at
      least 24 hours (P < 0.005). Of these 18 patients, 16 (89%) had a low serum IMg2+
      level. Total magnesium levels in contrast in all subjects were within normal
      range (0.70-0.99 mmol/L). No side effects were observed, except for a brief
      flushed feeling. Of the 8 patients with no relief, only 37.5% had a low IMg2+
      level. Patients demonstrating no return of headache or associated symptoms within
      24 hours of intravenous MgSO4 exhibited the lowest initial basal levels of IMg2+.
      Non-responders exhibited significantly elevated total magnesium levels compared
      to responders. Although most subcategories of headache types investigated (ie,
      migraine, cluster, chronic migrainous) exhibited low serum IMg2+ during headache
      and prior to intravenous MgSO4, the patients with cluster headaches exhibited the
      lowest basal levels of IMg2+ (P < 0.01). All headache subjects except for the
      chronic tension group exhibited rather high serum ICa2+/IMg2+ ratios (P < 0.01,
      compared to controls). CONCLUSIONS: Intravenous infusion of 1 gram of MgSO4
      results in rapid relief of headache pain in patients with low serum IMg2+ levels.
      Measurement of serum IMg2+ levels may have a practical application in many types
      of headache patients. Low serum and brain tissue ionized magnesium levels may
      precipitate headache symptoms in susceptible patients.

PMID- 8984088
TI  - SUNCT syndrome: duration, frequency, and temporal distribution of attacks.
AB  - Duration, frequency, and temporal distribution of attacks have been objectively
      estimated in 11 SUNCT patients (3 women and 8 men). The mean age at the time of
      the study was 69 years (range 52 to 81). The duration of a total of 348 attacks
      was measured from videotape records, polygraphic tracings, or by stopwatch. The
      duration of attacks ranged from 5 to 250 seconds, with an unweighted mean of 61
      seconds. Both frequency and exact timing of attacks were assessed in four
      patients who filled in a time chart with the exact onset of 585 consecutive
      attacks. The majority of attacks occurred during daytime, with a bimodal
      distribution; ie, morning and afternoon/evening peaks, and only a few attacks
      were noted at night (ie, 1.2% of the attacks). The unweighted mean frequency of
      attacks was 28 per day (range 6 to 77). Duration and timing of attacks in SUNCT
      syndrome may be of help in the differential diagnosis versus other disorders with
      the same localization, especially first division trigeminal neuralgia.

PMID- 8984089
TI  - Menstrual migraine with features of cluster headache. A report of 10 cases.
AB  - Ten patients with menstrually related migraine headaches and significant features
      of cluster headache are described. The mean age of onset of the headache was 29
      years. The duration of the pain was more typical for migraine, with an average of
      3 days. The pain was sharp with associated tear formation and nasal congestion.
      Eight of the women described significant nausea. Only one reported any type of
      cluster headache outside of the menstrual time. Four patients experienced tension
      headaches, and four also had migraines not related to menses (without cluster
      features). Preventive medications were generally not helpful. The abortive
      medications that did help included sumatriptan, Cafergot PB suppositories, and
      corticosteroids. Oxygen was useful in two patients. While analgesics did help
      three patients, lidocaine nasal spray was ineffective in four of the women.

PMID- 8984090
TI  - The prevalence of headache in Greece: correlations to latitude and climatological
      factors.
AB  - A questionnaire study on headaches, using a door-to-door survey, was carried out
      in a representative sample of the general Greek population, including 1737 men
      and 1764 women, from 15 to 75 years of age. The parameters evaluated included
      age, sex, education, socioeconomic status, region of domicile, frequency of
      headache, use of medication, medical consultation, and family history. Latitude
      and climatologic factors such as humidity, temperature, and atmospheric pressure
      were also investigated. Headaches were not classified because the interviewers
      were not specialists. Nineteen percent of men and 40% of women (mean 29%)
      suffered from headaches in the prior year. Headaches were more frequent in lower
      social classes, in people with less education, and in those between 45 and 64
      years of age. Nineteen percent of sufferers did not take any medication and 33%
      used medication every time that they had a headache, while 36% sought medical
      consultation. Twenty-nine percent of headache sufferers had a family history of
      headaches. Daily headache was present in 15% of headache sufferers. Humidity and
      atmospheric pressure were not correlated to headache frequency. However, in the
      northern areas of Greece, as well as in the regions with low mean temperature,
      more people suffered from daily headaches. These data may explain the lower 1
      year prevalence of headaches in other Greece as compared to the prevalence of
      headaches in other northern European countries.

PMID- 8984092
TI  - Migraine: a symptomatic case history.
AB  - Data from 28 years of the author's personal migraine diary are analyzed for
      patterns of aura and headache. A total of 186 occurrences of migraine are
      analyzed. A migraine-interval histogram suggests that, although the median
      interval between attacks is 37 days, there is an underlying cyclical interval of
      just 6 to 10 days. Distinct patterns are found for specific combinations of aura
      and symptoms depending on whether both sides, the right side, or the left side of
      the head were involved in the attack.

PMID- 8984091
TI  - Chronic cluster headache: provocation with carbon dioxide breathing and
      nitroglycerin.
AB  - Nine patients with chronic cluster headache were studied as to end-tidal PCO2,
      heart rate, blood pressure, common carotid artery blood flow, vascular
      resistance, and intensity and duration of pain before, during, and after
      breathing 6% CO2 in air for 6 minutes and before and after administration of 1 mg
      nitroglycerin sublingually. End-tidal PCO2 was low at rest without provocation
      indicating that chronic cluster headache patients hyperventilate. Carbon dioxide
      provocation induced an increase in common carotid artery blood flow. This
      provocation, previously shown to induce pain in episodic cluster headache
      patients, did not result in unilateral pain in chronic cluster headache patients.
      Nitroglycerin did not provoke any pain in 4 of 5 chronic cluster headache
      patients in contrast to the effects in episodic cluster headache patients in a
      cluster period. In one chronic cluster headache patient, a short-lasting attack
      of moderate pain intensity was provoked. The results agree with the hypothesis
      that chronic cluster headache patients have changed vascular reactivity due to
      permanent sympathicoplegia unilaterally in the middle fossa in contrast to
      episodic cluster headache patients who it has been suggested have a nonpermanent
      sympathicoplegia unilaterally in the same region.

PMID- 8984093
TI  - Clusterlike headache in a patient with a pituitary adenoma. With a review of the
      literature.
AB  - A man had left-sided atypical clusterlike headache for 9 years before he
      developed symptoms and signs consistent with acromegaly. Preoperative evaluation
      revealed raised levels of somatomedin C and growth hormone. An MR indicated a
      left-sided intrasellar mass measuring 8 x 7.5 x 10 mm. He underwent surgery and
      microscopy confirmed the diagnosis of a benign hypophyseal adenoma.
      Postoperatively, the acromegalic features regressed, and for the last 4 years the
      patient has been completely free from headache attacks. On pharmacological
      testing of the pupillary response to 1% and 5% phenylephrine and 2% tyramine
      solutions, there was no convincing evidence of persistent sympathetic dysfunction
      on the earlier symptomatic side.

PMID- 8984094
TI  - Stress during pregnancy is unrelated to headache change in migraineurs.

PMID- 8984095
TI  - Alphabetical hemoglobin variant list.

PMID- 8984096
TI  - A female sterile embryonic lethal in the maternally haplo-insufficient 21 B8.C1
      21 C8.D1 genomic region of Drosophila melanogaster.
AB  - Maternal hemizygosity of the 21 B8.C1-21 C8.D1 aristaless region of chromosome 2L
      of Drosophila melanogaster leads to high levels of embryonic mortality from the
      cross of Df(2L) al/+ females x +/+ males. The 21 B8.C1-21 C8.D1 polytene section
      therefore carries maternally active genes essential for embryogenesis. Selective
      screening for female sterile mutants against Df(2L) al yielded six alleles of a
      new female sterile embryonic lethal. This confirms the assumption that genomic
      regions that are maternally haplo-insufficient for normal embryogenesis house
      maternally active gene(s). It also demonstrates that mutational analysis of
      similar genomic regions can identify maternally acting embryonic lethal loci
      which escaped detection in spite of extensive screening experiments.

PMID- 8984097
TI  - Localization of landmarks and bands in the karotype of Sus scrofa domestica.
      Comparison between different classifications.
AB  - Representative RBG-banded chromosomes of Sus scrofa domestica and diagrammatic
      representation of the banding patterns at the 600 band stage are presented.
      Comparison between different classification systems has been performed. It is
      suggested that the data presented can be applied to gene mapping, localization of
      chromosome aberrations, comparative cytogenetics, and translation between
      different classification systems.

PMID- 8984098
TI  - Trisomy 8 and urogenital malformation in the ACI-rat.
AB  - ACI-rats are considered as a model for studying urogenital abnormalities. In
      order to recognise cytogenetic changes related to these abnormalities 50 male
      ACI/Seg rats were examined by means of gross macroscopic, histological, and
      karyotypical investigations. In six of the examined animals (12%) unilateral
      agenesis of the kidney and ipsilateral hypoplasia of the testes and seminal
      vesicles were observed. Isochromosome 8 and trisomy 8 (i8, +8) were observed in
      26.5% of karyotypes from the animals with kidney agenesis. Chromosome
      heteromorphisms such as 1p+, 3p+, 11p+, 12p+ were found in animals with and
      without apparent pathology. Because of the similarity between the phenotypical
      changes found in ACI-rats and in patients with familial renal agenesis (Potter's
      syndrome) and hereditary renal agenesis and aplasia (HRA), rat and human
      chromosomes associated with manifested renal malformations were examined by
      comparative cytogenetics and gene mapping.

PMID- 8984100
TI  - Immunohistochemical localization of apolipoprotein E in renal amyloidosis.
AB  - To clarify the role of apolipoprotein E (apo E) in the formation of amyloid
      deposits, we examined specimens from 11 patients with renal amyloidosis who
      underwent renal biopsy by an immunohistochemical method using a monoclonal
      antibody (murine IgG1). Apo E was distributed in the amyloid deposits of all
      patients in a pattern similar to that obtained with Congo red staining. Strong
      positive staining for apo E was found on the amyloid deposits in the glomeruli.
      These results suggest that apo E is a common constituent of amyloid fibrils and
      that it may be a useful marker for immunohistochemical studies of systemic
      amyloidosis including renal amyloidosis.

PMID- 8984099
TI  - Differential display of messenger RNA expressed in bronchoalveolar lavage cells
      in pulmonary sarcoidosis patients.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown origin. To clarify its
      pathogenesis, we searched for known or unknown genes which are specifically
      expressed in sarcoidosis. Bronchoalveolar lavage (BAL) cells from 18 patients
      with sarcoidosis and 8 patients with various lung diseases were analyzed by
      differential display method. mRNA was extracted from BAL cells and reverse
      transcribed with 12 kinds of anchored primer, which theoretically cover all
      mRNAs, followed by polymerase chain reaction (PCR) with the anchored primer and a
      10-mer arbitrary primer. PCR products were displayed on a polyacrylamide gel and
      fragments showing characteristic alterations in intensity between sarcoidosis and
      other patients were extracted, sequenced, and compared against Genbank and EMBL
      DNA data bases. One fragment was detected with specifically increased intensity
      and another disappeared in patients with sarcoidosis. These fragments were likely
      derived from unknown genes. CD44 and tumor necrosis factor (TNF-alpha) cDNA
      sequences were also detected as fragments commonly expressed in sarcoidosis. The
      cloned fragments with specifically increased or decreased intensity in
      sarcoidosis may provide important information on the pathogenesis of sarcoidosis,
      and the display pattern implies the potential usefulness of this method as a tool
      for diagnosis of the disease.

PMID- 8984101
TI  - The protective effect of low power He-Ne laser against erythrocytic damage caused
      by artificial heart-lung machines.
AB  - We studied the protective effects of low power He-Ne laser irradiation on
      erythrocytes against the damage caused by experimental artificial heart-lung
      machines. The erythrocyte suspension in a closed circuit was perfused with a
      roller pump. One of two circuits was used for laser treatment and the other for
      control. The laser group demonstrated significantly higher erythrocyte
      deformability and erythrocyte ATP levels, and lower free hemoglobin and lipid
      peroxide levels. A laser output power of 8.5 mW was most effective in protecting
      the erythrocytes. A further morphological finding using a scanning electron
      microscope showed fewer echinocytes and more discocytes in the laser group. This
      finding was consistent with the results of physiological and biochemical tests.
      Low power He-Ne laser irradiation was shown to protect human erythrocytes from
      the damage caused by an experimental artificial heart-lung machine, raising the
      possibility of the clinical application of low power He-Ne laser treatment during
      extracorporeal circulation in cardiovascular surgery.

PMID- 8984102
TI  - Dietary NaCl loading increases platelet Ca2+ discharge capacity in salt resistant
      essential hypertension.
AB  - To clarify the relationship between cellular Ca2+ handling and salt sensitivity,
      we evaluated cytosolic free Ca2+ ([Ca2+]i) in fura-2 loaded platelets isolated
      from 20 inpatients with essential hypertension. They were placed on a low sodium
      diet (50 mmol/day) for one week, followed by one week on a high sodium diet (340
      mmol/day). They were classified into salt-sensitive (SS, n = 8) or salt-resistant
      (SR, n = 12) based on changes in the mean blood pressure. During the low salt
      diet, basal [Ca2+]i, thrombin-evoked maximal Ca2+ responses, irrespective of the
      presence of 1 mM extracellular Ca2+, and ionomycin-sensitive intracellular Ca2+
      discharge capacity were similar in salt-sensitive and salt-resistant patients.
      Platelet basal [Ca2+]i were increased in both groups by salt loading (SS, from
      22.0 +/- 1.3 to 27.2 +/- 1.9 nM, p < 0.01; SR, from 20.1 +/- 0.8 to 24.4 +/- 1.3
      nM, p < 0.05). The thrombin-evoked maximal Ca2+ responses both in the presence
      and absence of extracellular Ca2+ were unchanged by high salt intake. The rate
      constant of decline in Ca2+ after the peak response to thrombin was larger in SR
      than that in SS during the high salt diet period (SS, 0.004 +/- 0.001 sec-1; SR,
      0.043 +/- 0.014 sec-1, p < 0.05). The intracellular Ca2+ discharge capacity was
      increased by excessive salt intake in the salt-resistant patients but was
      unchanged in the salt-sensitive patients (SS, from 658.1 +/- 52.8 to 639.6 +/-
      91.9 nM; SR, from 690.8 +/- 65.1 to 803.3 +/- 65.1 nM, p < 0.05). An increased
      intracellular Ca2+ discharge capacity may play, at least in part, a significant
      role in preventing the elevation of blood pressure after salt loading in salt
      resistant patients with essential hypertension.

PMID- 8984104
TI  - Spinal cord injures in children observed over many years.
AB  - The known salient features of spinal cord injuries in children are that 1) plane
      X-rays may not show dislocations or fractures, 2) many of these injuries are
      complete transections, 3) many injuries are located at the level of upper
      thoracic spine, and 4) the duration of spinal shock is short. Complications such
      as pressure sores occur just as easily in children as in adults and the injuries
      tend to be just as intractable. Complications characteristic in children with
      spinal cord injuries are spinal deformity and hip dislocation. In this paper, we
      describe a case involving a C7 spinal cord injury caused by a fall when the
      patient was 3 years old. We have observed the physical complications for 15 years
      following that injury. We also report on other observed cases of spinal cord
      injury.

PMID- 8984103
TI  - Effect of N-feruloyl tyramine (an analogue of tyramine) on inwardly rectifying
      potassium channel in frog ventricular myocytes.
AB  - Electrophysiological effects of N-feruloyl tyramine (NFT), an analogue of
      tyramine, on potassium currents in frog ventricular myocytes were examined using
      single-channel recording and whole-cell voltage clamp technique. Extracellular
      application of NFT induced a concentration-dependent decrease of macroscopic
      inward rectifier potassium current (iK1) with ID50 of 198 microM, while tyramine
      (100 microM) was ineffective in producing an inhibitory effect on iK1. NFT
      reduced the mean open time of iK1 to 1.3 ms from 3.1 ms in control without
      affecting the amplitude of single-channel conductance. It is indicated that boi
      containing NFT produces a prolongation of the plateau phase caused by the
      suppression of inwardly rectifying K channel. Thus, this prolongation may induce
      an increase in the inflow of Ca ions, which in turn leads to a positive inotropic
      effect.

PMID- 8984105
TI  - [Atypical form of pigmented villonodular synovitis of the knee containing
      calcifications].
AB  - A case of atypical pigmented villonodular synovitis containing calcifications in
      the left knee of a young female is presented. The patient underwent total
      synovectomy and no recurrence was observed over a two-year follow-up period. The
      purpose of this study is to provide a review of the literature which shows almost
      invariably the absence of calcifications in the disorder. The authors compare the
      contribution of the different imaging modalities for the diagnosis of the entity.

PMID- 8984107
TI  - [Rt-PA thrombolysis in the treatment of massive pulmonary embolism].
AB  - We present the case of a young comatose female patient in whom a massive
      pulmonary embolism was diagnosed by pulmonary angiography. During the
      angiography, not only successful thrombolytic therapy with recombinant human
      tissue-type plasminogen activator (rt-PA) (100 mg) was performed, but measuring
      of the pulmonary artery pressures, oxygen and carbon dioxide levels was also
      possible. Thrombolysis seems to be a good alternative to surgical thrombectomy.

PMID- 8984106
TI  - [Multiple congenital tarsal synostoses].
AB  - Tarsal coalition is an abnormal fusion of two or more tarsal centers. Talo
      calcaneal and calcaneo-navicular coalition are the most frequent types. If
      multiple tarsal coalition is suspected, computed tomography with sagittal
      reconstruction is the best method for diagnosis.

PMID- 8984109
TI  - [Imaging of acquired pathologies of the thoracic aorta].
AB  - For many years, imaging of thoracic aorta has been dominated by angiography.
      Development of new imaging modalities has modified the diagnostic approach to
      thoracic aortic pathology. The knowledge of the advantages and limitations of
      each technique enables a better choice for patient evaluation, in particular
      under emergency conditions. This study is based on a review of the literature and
      reports the authors' experience.

PMID- 8984110
TI  - [Emergency treatment of hemobilia using embolization].
AB  - Embolotherapy has gained widespread acceptance as the modality of choice for the
      management of hemobilia because of its safety profile. Our case reports a
      successful transcatheter embolization of the right hepatic artery aneurysm
      causing hemobilia in a patient in hemodynamic instability.

PMID- 8984108
TI  - [Embolization of traumatic hemorrhages].
AB  - This retrospective study of 17 patients evaluates the effectiveness of
      angiographic embolization as a treatment for traumatic hemorrhage. Bleeding was
      caused by external trauma in 8 patients and by iatrogenic trauma in 9 patients.
      Embolization was only performed if contrast-extravasation or a pseudoaneurysm
      could be visualized. In 16 of 17 patients immediate technical and clinical
      success was achieved. Over a 30-day follow-up period 3 patients died of multi
      organ failure, toxic hepatitis and neurotrauma. In conclusion, embolization is a
      highly efficient and safe technique.

PMID- 8984111
TI  - [Placing of a Nitiol Memotherm prosthesis: personal experience].
AB  - The authors report their experience in the placement of a new Nitinol stent.
      Thirty eight stents were placed in 28 iliac arteries, 3 superficial femoral
      arteries, 1 popliteal artery, 2 subclavian arteries, and 2 veins of hemodialysis
      fistulae. The primary success rate was 100%, but several angioplasty balloons
      have been ruptured due to the specific configuration of the stent. The mean
      follow-up period was 6 months. Memotherm placement is an easy procedure, but the
      specific structure of the device makes the manipulation of the angioplasty
      balloons delicate, especially in tortuous vessels.

PMID- 8984112
TI  - Ultrastructure of the alimentary tract of third-stage larvae of Litomosoides
      carinii.
AB  - The ultrastructural morphology of the alimentary tract of the third-stage larvae
      of Litomosoides carinii (Nematoda: Filarioidea) is described. The oesophagus
      possesses the characteristic tri-radiate lumen and is lined by cuticle. Teh lumen
      of the oesophagus is tightly occluded anteriorly by particulate material and
      posteriorly at the oesophagointestional junction. Three glands are present in the
      glandular region, one dorsal and two subventral. These glands contain secretory
      granules with similar morphological and staining properties. The lumen of the
      intestine is ill-defined without microvilli and apparently non-functional. It is
      likely that the larvae feed via the transcuticular route.

PMID- 8984114
TI  - Members of the European Association for the Study of the Liver, 1996.

PMID- 8984113
TI  - The effect of chitin synthesis inhibitors on the development of Brugia malayi in
      Aedes aegypti.
AB  - Two chitin synthesis inhibitors (CSIs) viz., triflumuron and hexaflumuron
      interfere++ with the development of Brugia malayi in Aedes aegypti (a black-eyed
      Liverpool strain). The development of B. malayi was slow in both the treated
      populations and the infection rate, infectivity rate and L3 load per mosquito
      decreased significantly (P < 0.001) in comparison with untreated controls.
      Hexaflumuron was found to be more inhibiting than triflumuron.

PMID- 8984115
TI  - Proceedings of the 4th International Conference on Prevention of Infection. Nice,
      France, May 6-7, 1996.

PMID- 8984116
TI  - Bibliography of the current world literature in hypertension.

PMID- 8984118
TI  - Exercise lowers blood pressure--sometimes? Or did Pheidippides have hypertension?

PMID- 8984117
TI  - The role of exercise in blood pressure control: supportive evidence.
AB  - Epidemiological studies suggest an inverse relationship between physical activity
      or fitness and blood pressure. In controlled intervention studies, the weighted
      net change in conventional blood pressure caused by dynamic aerobic training
      averaged -5.3 mmHg for systolic and -4.8 mmHg for diastolic blood pressure. The
      considerable interstudy variation in the blood pressure response can be partly
      explained by the more pronounced effect in hypertensive patients compared with
      the results in normotensive subjects. When only studies that used a random
      procedure and some follow-up study of the controls were included, the blood
      pressure-lowering effect of training was significant only in hypertensives. The
      same pattern is emerging for daytime blood pressure in studies that applied
      ambulatory pressure monitoring: night-time pressure was usually not affected by
      training. In conclusion, despite shortcomings in many individual studies, the
      overall results suggest that dynamic aerobic training may lower conventional and
      daytime blood pressure in adults with elevated blood pressure at baseline.

PMID- 8984119
TI  - Factors influencing validation of ambulatory blood pressure measuring devices.
AB  - With the introduction of 24 h ambulatory blood pressure monitoring into clinical
      practice a vast market for ambulatory blood pressure monitoring devices has been
      created. To satisfy this market manufacturers are producing an array of
      ambulatory blood pressure monitoring devices. There is no obligation on
      manufacturers to have such devices validated independently, even though two
      national protocols, one from the British Hypertension Society (BHS) and the other
      from the Association for the Advancement of Medical Instrumentation (AAMI), call
      for independent validation and state the means of doing so. However, many factors
      can influence the validation procedure. They include compliance to the protocol
      being employed; the accuracy of the standard; establishing precisely the model
      being validated; the influences of blood pressure level, age and exercise on
      device accuracy; the provisions necessary for special populations, such as
      pregnant women, the elderly and children; the influence of oscillometric versus
      Korotkoff sound detection and electrocardiographic gating on comparative
      measurements; the assessment of performance as distinct from accuracy; and the
      relevance of general factors, such as the algorithm being employed and computer
      compatibility. Forty-three ambulatory blood pressure monitoring devices have been
      marketed for ambulatory blood pressure measurement and of those only 18 have been
      validated according to either the BHS or the AAMI protocol. The influence of the
      factors listed above on the validation studies of those devices will be
      considered and the relevance of validation procedures to the clinical use of
      ambulatory blood pressure monitoring devices will be discussed.

PMID- 8984120
TI  - Fasting inhibits natriuretic peptides clearance receptor expression in rat
      adipose tissue.
AB  - OBJECTIVE AND DESIGN: The early phase of weight loss induced by fasting is
      associated with diuresis, natriuresis and reduction in blood pressure through
      unclear mechanisms. Atrial natriuretic peptide (ANP) is a cardiac hormone with
      potent natriuretic, diuretic and hypotensive effects mediated by 'biologically
      active' receptors (NPr-A). A second type of receptor mediates the clearance of
      ANP (the clearance receptor, NPr-C). Since NPr-C appears to be abundant in
      adipose tissue, we analysed NPr-C and NPr-A gene expression in white and brown
      adipose tissue (WAT and BAT) as well as in renal cortex of fasting rats. Plasma
      ANP, cyclic GMP and aldosterone were also measured. METHODS: Twelve male Wistar
      rats were deprived of food for about 50 h, and 12 other rats were fed ad libitum.
      Periepididymal WAT, interscapular BAT and left renal cortex were used for RNA
      extraction and northern blot analysis with rat NPr-C and NPr-A complementary DNA
      probes labelled with 32P-dCTP. Densitometric analysis of hybridization signals
      was corrected by beta actin expression before statistical analysis. Blood was
      drawn for ANP, cyclic GMP (cGMP) and aldosterone radioimmunoassays, which were
      also measured in a group of six rats deprived of food for 25 h. RESULTS: A
      dramatic decrease in NPr-C steady-state messenger RNA levels was observed both in
      WAT (about 3.6-fold, P < 0.001) and in BAT (about threefold, P < 0.01), but
      fasting did not affect the expression of NPr-A in adipose tissues. In the renal
      cortex NPr-C and NPr-A messenger RNA levels were unaffected by fasting. ANP and
      aldosterone levels were reduced after fasting whereas cyclic GMP was increased at
      25 h, but the differences did not reach statistical significance. CONCLUSIONS:
      Fasting exerts a tissue-specific and gene-specific suppression of NPr-C gene
      expression in adipose tissue that appears to be accompanied by an increased
      biological activity of ANP. The natriuresis and diuresis and reduction of blood
      pressure induced by fasting might result from a reduced expression of NPr-C in
      adipose fat pads.

PMID- 8984123
TI  - Do immune system changes have a role in hypertension?
AB  - There is growing evidence to indicate that there is a strong association between
      changes in the immune system and the development of hypertension in both animal
      models and humans. Alterations in immune function in hypertension are generally
      accompanied by an increase in the level and secretion of immunoglobulin, a
      decrease in the number and function of T-lymphocytes, genetic predisposition,
      auto-antibodies against nuclear structure, smooth muscle cells, native thymus
      tissue and G-protein-coupled cardiovascular receptors. Although there is evidence
      from a variety of observations to suggest that an abnormal immune system is
      involved in the pathogenesis of hypertension, the immunological mechanism and the
      specific role of changes in the immune system in the development of hypertension
      have not been elucidated.

PMID- 8984121
TI  - Mapping and sequence analysis of the gene encoding the beta subunit of the
      epithelial sodium channel in experimental models of hypertension.
AB  - OBJECTIVE: To investigate whether mutations in the beta subunit of the epithelial
      sodium channel (Scnn1b) contribute to the pathogenesis of hypertension in the
      spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive rat. DESIGN: We
      determined the chromosome location of the rat Scnn1b gene, tested for
      cosegregation with blood pressure, and sequenced near full-length Scnn1b
      complementary DNAs (cDNAs) from SHR and Dahl salt-sensitive rats. METHODS:
      Chromosome mapping was performed by somatic cell hybrid analysis and by linkage
      analysis in recombinant inbred strains derived from SHR and Brown-Norway rats.
      Cosegregation analysis was performed by testing for correlations between blood
      pressure and Scnn1b genotypes in these strains. DNA sequencing was performed on
      cDNAs prepared from reverse-transcribed messenger RNA derived from rat kidney.
      RESULTS: The Scnn1b gene was closely linked to the Sa gene on rat chromosome 1.
      Blood pressure correlated significantly with Scnn1b gene in the recombinant
      inbred strains. Analysis of near full-length Scnn1b cDNAs from SHR and Dahl rats
      failed to reveal any coding sequence mutations that could affect the predicted
      amino acid sequence of the Scnn1b protein. CONCLUSION: The Scnn1b gene maps near
      the Sa gene in a region of rat chromosome 1 involved in the inherited control of
      blood pressure. If disordered activity of the epithelial cell sodium channel
      contributes to the pathogenesis of hypertension in the SHR or Dahl models, it
      must stem from genetic lesions in sequences that regulate Scnn1b function or in
      sequences important to the structure or function of the other sodium channel
      subunits.

PMID- 8984122
TI  - Regulation of 11 beta-hydroxylase cytochrome p450 expression by cholesterol in
      spontaneously hypertensive rats.
AB  - OBJECTIVE: To investigate whether hypercholesterolaemia interferes with the
      expression of the enzymes involved in steroid biosynthesis in the adrenal cortex.
      METHODS: Twenty-four 5-week-old male spontaneously hypertensive rats (SHR) were
      randomly assigned to a high (1%) cholesterol diet (n = 8) or to a matched
      cholesterol-free diet (n = 8) for 6 weeks. A third group (n = 8) was studied
      after 2 weeks of washout from the high-cholesterol intake. A cohort of age- and
      sex-matched normotensive Wistar-Kyoto (WKY) rats (n = 24) underwent the same
      treatments and was used as a control. RESULTS: In SHR cholesterol feeding reduced
      urinary sodium excretion (0.8 +/- 0.1 versus 1.4 +/- 0.1 mmol/24 h in the
      cholesterol-free group), increased plasma aldosterone levels (299 +/- 60 versus
      154 +/- 24) and reduced plasma corticosterone levels (142 +/- 21 versus 278 +/-
      35 ng/ml). Those responses were associated with a reduction of 11 beta
      hydroxylase cytochrome P450 messenger RNA (mRNA) in the adrenal cortex (-52.3 +/-
      3.4%) whereas aldosterone synthase mRNA remained unchanged. That effect and the
      changes in electrolyte excretion and steroid levels were no longer detectable
      after withdrawal of the diet. In WKY rats high-cholesterol diet induced no
      significant changes in urinary electrolyte excretion, steroid levels and
      expression of 11 beta-hydroxylase cytochrome P450 and aldosterone synthase in the
      adrenals. CONCLUSIONS: The present results indicate that in SHR
      hypercholesterolaemia selectively interferes with the adrenal steroid
      biosynthetic pathway by reducing the expression of 11 beta-hydroxylase, leading
      to accumulation of mineralocorticoids and sodium retention.

PMID- 8984124
TI  - Dietary macronutrients and blood pressure in southwestern China.
AB  - OBJECTIVES: To study the relationship between dietary macronutrients and blood
      pressure. DESIGN: A cross-sectional study. SETTING: Liangshan, southwestern
      China. PARTICIPANTS: Three hundred and twelve Yi farmers living in a remote
      mountainous area, and 264 Yi migrants and 251 Han people living in an urban
      setting. MAIN OUTCOME MEASUREMENTS: Blood pressure and dietary nutrient intake,
      obtained by asking the subjects to recall their nutrient consumption during the
      previous 24 h, were measured on three consecutive days. RESULTS: After adjusting
      for age, body mass index, alcohol use, urinary excretion of sodium, total energy
      intake and area of residence and after correcting for the effects of regression
      dilution bias, a 1 SD higher intake of dietary total protein (39 g) was
      associated with lower systolic (-3.55 mmHg), and diastolic (-2.16 mmHg) blood
      pressures. Likewise, a 1 SD higher fiber intake (10 g) was significantly
      associated both with a lower systolic (-2.20 mmHg) and with a lower diastolic (
      2.08 mmHg) blood pressure. CONCLUSION: Diets higher in protein and fiber content
      are associated with a lower blood pressure in the present population sample. The
      present results indicate that dietary intake of macronutrients might be important
      in the development and prevention of high blood pressure.

PMID- 8984125
TI  - On the existence of functional angiotensin II receptors on vascular sympathetic
      nerve terminals in the human forearm.
AB  - OBJECTIVE: The existence of presynaptic angiotensin II receptors, modulating the
      release of the sympathetic neurotransmitter norepinephrine, was examined in the
      perfused human forearm model. DESIGN AND METHODS: In three groups out of a total
      of 20 healthy volunteers, intra-arterial infusions of tracer amounts of tritiated
      norepinephrine were given to measure forearm spillover and total plasma
      appearance rate of norepinephrine during intra-arterial infusions of angiotensin
      II (0.02, 0.2 and 2 ng/kg per min), methoxamine (0.08, 0.4 and 2 micrograms/kg
      per min) to produce vasoconstriction by stimulating alpha 1-adrenoceptors and
      saralasin (0.5 ng/kg per min) to block angiotensin II receptors. Postganglionic
      sympathoneural activity was stimulated by intravenous infusion of sodium
      nitroprusside (about 1.3 ng/kg per min) or attenuated by intravenous infusion of
      trimethaphan (about 1 mg/min). RESULTS: Angiotensin II failed to increase the
      spillover and total plasma appearance rate of norepinephrine, when given without
      additional treatment or during sodium nitroprusside or trimethaphan
      administration. In contrast, the spillover of norepinephrine even decreased
      during angiotensin II administration, both before and during intravenous sodium
      nitroprusside administration, probably because of angiotensin II-induced forearm
      vasoconstriction. Similar vasoconstrictor doses of angiotensin II and methoxamine
      produced similar changes in spillover and total plasma appearance rate of
      norepinephrine. The highest dose of angiotensin II increased diastolic blood
      pressure by 9% and decreased the pulse rate by 6%. Saralasin affected the
      spillover and total plasma appearance rate of norepinephrine neither before nor
      during intravenous sodium nitroprusside infusion. CONCLUSION: The present results
      fail to support the view that angiotensin II receptors exert stimulatory
      modulatory effects on norepinephrine release from sympathetic nerves in the human
      forearm, at rest or during changes in sympathoneural outflow.

PMID- 8984126
TI  - Altered cardiovascular responses to purinergic A2 stimulation in the nucleus
      tractus solitarius of spontaneously hypertensive rats.
AB  - OBJECTIVE: To investigate the cardiovascular effects of adenosine A2 receptor
      stimulation in the nucleus tractus solitarius and whether these effects are
      altered in hypertension. DESIGN AND METHODS: Ten- or 11-week-old spontaneously
      hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats were anaesthetized with
      urethane. Adenosine (100 ng) or adenosine A2 agonist (2-octynyladenosine, 5 ng)
      were micro-injected (50 nl) into the nucleus tractus solitarius. Blood pressure
      and heart rate were measured from a femoral artery. Sympathetic nerve activity
      was recorded from the abdominal splanchnic nerve. RESULTS: Blood pressure, heart
      rate and sympathetic nerve activity were consistently decreased after the micro
      injection of adenosine into normotensive rats. Changes from the baseline in blood
      pressure, heart rate and sympathetic nerve activity were significantly smaller in
      SHR than in WKY rats (blood pressure: SHR -5.6 +/- 2.1% versus WKY rats -20.0 +/-
      2.1%; heart rate: SHR -5.4 +/- 0.88% versus WKY rats -9.2 +/- 2.3%; sympathetic
      nerve activity: SHR -5.5 +/- 1.1% versus WKY rats -21 +/- 2.8%). Micro-injection
      of an A2 agonist into the nucleus tractus solitarius also decreased blood
      pressure and heart rate, and those responses were not inhibited by pretreatment
      with an adenosine A1-specific antagonist. The response induced by micro-injection
      of A2 agonist into the nucleus tractus solitarius was significantly smaller in
      SHR than in WKY rats, whereas the changes in heart rate did not differ
      statistically (blood pressure: -23.4 +/- 4.7% versus -10.8 +/- 2.1%; heart rate: 
      12.1 +/- 1.2% versus -13.6 +/- 2.1%). CONCLUSION: The present results suggest
      that stimulation of adenosine A2 receptors in the nucleus tractus solitarius
      decreases both blood pressure and inhibitory sympathetic nerve activity and that
      those inhibitory responses to adenosine in the nucleus tractus solitarius are
      deranged in SHR.

PMID- 8984128
TI  - Influence of left ventricular hypertrophy on heart period variability in patients
      with essential hypertension.
AB  - OBJECTIVE: To evaluate whether left ventricular hypertrophy in hypertensive
      patients is associated with a greater impairment of sympathovagal balance
      assessed by means of heart period variability. DESIGN AND METHODS: Forty
      hypertensive patients, 20 with echocardiographic evidence of left ventricular
      hypertrophy and 20 without, and 20 control subjects, were subjected to 24 h blood
      pressure monitoring and Holter recording on 2 consecutive days. Power spectrum
      analyses of heart period variability were performed utilizing the fast Fourier
      transform algorithm. RESULTS: No difference was detectable in 24 h, daytime and
      night-time blood pressure values between hypertensive patients with and without
      left ventricular hypertrophy. Low- and high-frequency powers were higher in
      controls than in hypertensives; in particular, low-frequency power showed a
      progressive decrease through control subjects and hypertensives without and with
      left ventricular hypertrophy. Furthermore, significant negative correlations were
      found between left ventricular mass index and low- and high-frequency power. No
      difference was detectable in ultra-low- and very low-frequency power. During
      daytime low- and high-frequency power were higher in controls than in
      hypertensives; during night-time, low- and high-frequency power increased
      significantly in all groups and low-frequency power was still higher in control
      subjects. CONCLUSIONS: Considering that, when analysed over 24 h Holter
      recording, low- and high-frequency power both reflected the parasympathetic
      modulation of heart rate, the present results demonstrate a parasympathetic
      withdrawal in hypertension; this sympathovagal imbalance is greater in patients
      with cardiac hypertrophy and is related to the increase in left ventricular mass.

PMID- 8984127
TI  - Postprandial hypotension and orthostatic blood pressure responses in elderly
      Parkinson's disease patients.
AB  - OBJECTIVE: To investigate the change in systolic blood pressure (SBP) induced by
      meals and to compare their impact on the orthostatic SBP response in elderly
      Parkinson's disease with that in control patients. DESIGN: Ten elderly patients
      suffering from Parkinson's disease were compared with 10 age-matched elderly
      control patients. METHODS: The postprandial SBP change was measured by means of
      ambulatory blood pressure monitoring with the patient in the supine position.
      Orthostatic SBP responses were measured the next day by means of active standing
      and passive head-up tilting tests performed before and after the patients had
      their lunch. RESULTS: In Parkinson's disease patients, a postprandial SBP drop of
      27 mmHg in the supine position was found compared with a drop of 8 mmHg in
      controls. In Parkinson's disease patients, that drop was moderately correlated to
      the orthostatic SBP responses and significantly correlated to the preprandial
      supine baseline SBP level. The orthostatic fall in SBP was greater with passive
      than with active standing and with both it was greater in Parkinson's disease
      patients than in the control subjects. The fall in orthostatic blood pressure was
      reduced by a previous meal. In contrast, there was no difference in orthostatic
      heart rate responses between the patients and the controls. CONCLUSIONS:
      Parkinson's disease patients demonstrated a significant postprandial drop in SBP
      and a tendency towards orthostatic hypotension, which was not worsened by the
      meal, probably owing to a stronger sympathetic activation. Postprandial supine
      SBP change and orthostatic SBP responses were only moderately associated in
      Parkinson's disease patients. In addition to autonomic dysfunction, an increased
      baseline SBP level might contribute to both phenomena.

PMID- 8984129
TI  - Angina pectoris by Rose questionnaire does not predict cardiovascular disease in
      treated hypertensive patients.
AB  - OBJECTIVE: To determine the predictive value of angina pectoris diagnosed by Rose
      questionnaire for cardiovascular disease among treated hypertensives. METHODS:
      The cardiovascular experience of 4093 patients who had no history of
      cardiovascular disease and had been administered the Rose questionnaire for
      angina in a worksite treatment program was evaluated. RESULTS: Among 2659 men and
      1434 women of similar age (53 versus 54 years), the race distribution was 44
      versus 31% whites, 27 versus 41% blacks and 29 versus 28% Hispanics. Overall, the
      prevalence of angina by Rose questionnaire in women (15%) was twice that in men
      (7%) in all three races, with Hispanics having the highest (20 versus 10%)
      prevalence. Those with angina (Rose-plus) and those without (Rose-minus) had
      similar initial and final blood pressures. In 4.0 years of average follow-up
      study, the crude incidence rates (per 1000 person-years) of the recorded 120
      myocardial infarctions and 35 strokes did not differ significantly between Rose
      plus and Rose-minus patients, except for myocardial infarction in Hispanic men
      (20.5 versus 5.9). When myocardial infarction incidence was adjusted for age
      within each sex-race subgroup, only Rose-plus Hispanic men had a significantly
      greater relative risk with Rose-minus as referent (relative risk 3.13, 95%
      confidence interval 1.31-7.50). Overall, in the Cox proportional hazards
      regression model, angina by Rose questionnaire was not predictive of myocardial
      infarction after accounting for other recognized risk factors. CONCLUSIONS: The
      present data suggest that the Rose questionnaire as a diagnostic tool for angina
      is not predictive of subsequent clinical events among treated hypertensive
      patients.

PMID- 8984130
TI  - Alterations of cardiac contractile function are related to changes in membrane
      calcium transport in spontaneously hypertensive rats.
AB  - OBJECTIVE: Transport activities of cardiac sodium-calcium exchange and
      sarcoplasmic reticulum calcium ATPase were measured biochemically in
      spontaneously hypertensive rats (SHR) with hypertrophied myocardium and in
      normotensive Wistar-Kyoto (WKY) rats and it was tested whether possible
      differences have consequences for the contractile properties of papillary muscle.
      METHODS: Sarcolemmal sodium-dependent calcium transport via sodium-calcium
      exchange and oxalate-supported sarcoplasmic reticulum calcium uptake were
      measured in left ventricular membranes of 22-week-old rats. Postextrastimulatory
      potentiated contractions, postrest potentiated contractions, the twitch-to-twitch
      decay of those potentiations and the response to increasing stimulation frequency
      of left ventricular papillary muscles were analysed. RESULTS: Compared with WKY
      rats we found in SHR: a significant increase in sodium-calcium exchange (65%) and
      in sarcoplasmic reticulum calcium uptake (24%); a steeper twitch-to-twitch decay
      in postextrastimulatory potentiated contractions and postrest potentiated
      contractions, suggesting a lower calcium fraction recirculating between
      myofilaments and sarcoplasmic reticulum and, consequently, a relatively higher
      calcium efflux via sodium-calcium exchange; a stronger rest-dependent decrease in
      recirculating calcium fraction in postrest potentiated contractions accompanied
      by accelerated relaxation, suggesting an increasing driving force for calcium
      extrusion via sodium-calcium exchange, probably caused by decreasing
      intracellular sodium during rest; a greater transient decrease in peak force of
      subsequent twitches after postrest potentiated contractions below pre
      interventional level, indicating higher cellular calcium loss; and a smaller
      negative inotropic effect in response to doubling of stimulation rate as a
      manoeuvre to increase the intracellular sodium level. CONCLUSION: In SHR, the
      contractile properties suggest an increased contribution of sodium-calcium
      exchange to cellular calcium removal, which is strongly supported by the enhanced
      sodium-calcium exchange activity in cardiac membrane vesicles.

PMID- 8984131
TI  - ACE inhibitor ramipril is more effective than the beta-blocker atenolol in
      reducing left ventricular mass in hypertension. Results of the RACE (ramipril
      cardioprotective evaluation) study on behalf of the RACE study group.
AB  - OBJECTIVES: To compare the effect of the angiotensin converting enzyme (ACE)
      inhibitor ramipril with that of the beta-blocker atenolol on reversal of left
      ventricular hypertrophy, on blood pressure and on other echocardiographic
      parameters. DESIGN: The study was conducted in accord with the PROBE (prospective
      randomized open blinded endpoint) design. Randomized treatment either with
      ramipril or with atenolol was continued for 6 months, and echocardiograms were
      recorded before and after 3 and 6 months of treatment. The echo tracings were
      blindly evaluated in a single reading centre. METHODS: M-mode, two-dimensional
      guided echocardiography was used to measure left ventricular wall thicknesses and
      dimensions, from which left ventricular mass was calculated, according to the
      Penn convention. RESULTS: Of 193 patients at 16 centres, 111 had echocardiograms
      that could be quantitatively evaluated. The primary analysis of the study was
      performed using data from those patients. In addition, echocardiograms of 88
      patients were analysed on an 'according to protocol' basis (patients with preset
      values of left ventricular mass). Systolic and diastolic blood pressures were
      significantly reduced both by ramipril and by atenolol without any significant
      difference between the two drug treatments. The heart rate was significantly
      reduced by atenolol only. Both the 'primary' and the 'according to protocol'
      analyses showed that the left ventricular mass was significantly reduced by
      ramipril only. Comparison between treatments according to a multivariate analysis
      demonstrated a significantly greater reduction in left ventricular mass during
      ramipril than during atenolol treatment. CONCLUSIONS: The present study is the
      first of suitably large size in which a direct comparison of the effects of an
      ACE inhibitor and a beta-blocker on echocardiographic left ventricular mass has
      been performed. It has demonstrated that ramipril is more effective than atenolol
      in reversing left ventricular hypertrophy in essential hypertensive patients.

PMID- 8984132
TI  - Albuminuria predicts renal functional outcome after intervention in atheromatous
      renovascular disease.
AB  - BACKGROUND: Atheromatous renovascular disease is increasingly recognized as a
      cause of renal failure; however, the benefit of intervention on renal function
      outcome cannot be clearly anticipated. OBJECTIVE: To identify reliable
      predictor(s) of renal functional outcome after revascularization in patients with
      atheromatous renovascular disease. DESIGN: The effect of percutaneous
      transluminal renal angioplasty (n = 5) or surgery (n = 18) on glomerular
      filtration rate ([99mTc]-diethylene triaminopenta-acetic acid clearance) and
      renal haemodynamics was prospectively assessed in 23 patients with atheromatous
      renovascular disease (unilateral occlusion in five, unilateral stenosis in four,
      stenosis of a single kidney in five, unilateral occlusion associated with
      contralateral stenosis in six, bilateral stenosis in three). Renal function was
      altered in 18 patients. RESULTS: At early follow-up study (5 +/- 1 months) after
      intervention, glomerular filtration rate improved (i.e. increased by more than
      15%) in six patients, deteriorated in five and remained unchanged in 12 patients.
      The change in glomerular filtration rate associated with intervention was
      inversely correlated with the pre-intervention level of urinary albumin excretion
      and positively with the change in effective renal plasma flow after intervention.
      Stepwise regression analysis showed that pre-intervention urinary albumin
      excretion was the only predictor of the glomerular filtration rate response to
      intervention. At late follow-up study (32 +/- 6 months, n = 13), glomerular
      filtration rate was stable compared with early follow-up determination in non
      proteinuric patients whereas it had deteriorated further in proteinuric patients.
      CONCLUSION: In patients with atheromatous renovascular disease, albuminuria may
      be considered as a marker of pre-existing intra-renal vascular and glomerular
      damage and a reliable predictor of renal functional outcome after intervention.

PMID- 8984133
TI  - Comparison of the angiotensin II antagonist losartan with the angiotensin
      converting enzyme inhibitor enalapril in patients with essential hypertension.
AB  - OBJECTIVE: To evaluate the blood pressure lowering efficacy as well as
      tolerability and safety of the angiotensin II antagonist losartan compared with
      that of the angiotensin converting enzyme inhibitor enalapril in patients with
      mild-to-moderate essential hypertension. DESIGN AND METHODS: The study was a
      multicentre, double-blind, double-dummy, randomized, parallel study. Patients (n
      = 407) with diastolic blood pressure > or = 95 and < or = 120 mmHg at the end of
      a 2-week baseline placebo period were randomly allocated to receive either 50 mg
      losartan once a day or 20 mg enalapril once a day for 12 weeks. Blood pressure,
      clinical and laboratory safety, specific symptoms including coughing determined
      using a symptoms questionnaire and metabolic variables were examined at baseline
      and at weeks 6 and 12. RESULTS: Both losartan and enalapril decreased systolic
      and diastolic blood pressure from baseline at weeks 6 and 12. Blood pressure
      changes from baseline at trough (22-26 h after the dose) did not differ between
      the two groups in the per-protocol analysis. Response to treatment at trough was
      excellent or good (diastolic blood pressure < 90 mmHg or reduction in diastolic
      blood pressure of 10 mmHg) in 51 and 53% of the patients in the losartan and
      enalapril groups, respectively. Enalapril administration increased dry coughing
      symptoms whereas losartan did not. The incidence of dry coughing was 1.0 and
      12.2% as a spontaneously reported discomfort at week 12 and 3.0 and 15.1% as a
      clinical adverse experience in the losartan and enalapril groups, respectively.
      The difference from baseline at week 12 in the incidence of dry coughing between
      the two groups was 14.9% as a specific symptom in the symptoms questionnaire.
      Losartan reduced serum uric acid concentration, whereas effects on other
      metabolic parameters did not differ between the groups. CONCLUSIONS: Losartan is
      an effective and well-tolerated antihypertensive drug showing similar blood
      pressure-lowering efficacy to that of enalapril at trough. However, in contrast
      to enalapril, losartan does not increase the incidence of dry coughing. Thus, the
      angiotensin II antagonist losartan provides a promising new approach to treatment
      of hypertension.

PMID- 8984135
TI  - Does drug treatment improve survival in mild-to-moderate hypertension?

PMID- 8984134
TI  - Meta-analysis and the Hippocratic principle of primum non nocere--authors' reply.

PMID- 8984136
TI  - [Incidence of ovarian hyperstimulation syndrome following therapy of patients
      with infertility and the treatment and outcome].

PMID- 8984137
TI  - Progress against cancer.

PMID- 8984138
TI  - Cover-up. Acute inferior wall myocardial infarction.

PMID- 8984140
TI  - The journal 150 & 100 years ago. March 1846 and 1896.

PMID- 8984139
TI  - Congenital midline nasal masses: dermoids, gliomas, and encephaloceles.
AB  - Congenital midline nasal masses are rare entities and therefore easily
      misdiagnosed or missed altogether. This article reviews the three most common
      congenital midline nasal masses: dermoids, gliomas, and encephaloceles.
      Discussion entails embryology, diagnosis, radiologic workup, surgical therapy,
      and complications.

PMID- 8984141
TI  - [General principles of oxygen transport in the venous wall].
AB  - OBJECTIVE: To review the mechanisms of oxygen transport in the walls of arteries
      and veins and to consider whether oxygen transport might limit oxygen consumption
      in the venous wall. METHODS: (i) To review evidence for the contributions of
      transport from the vascular lumen and transport from the vasa vasorum to the
      supply of oxygen to the walls of arteries. (ii) To use the general principles of
      oxygen diffusion through tissues to extrapolate the findings of investigations of
      oxygen transport into arterial walls to transport into the walls of the larger
      veins. RESULTS AND DISCUSSION: The magnitude of oxygen transport from the vessel
      lumen into the vessel wall is dependent on the partial pressure of oxygen (PO2)
      in the vessel lumen. While luminal PO2 is constant and high in arteries, it is a
      physiological variable in veins of healthy people. In larger veins, there is
      evidence that flow in the vasa vasorum increases as PO2 in the vessel lumen
      falls. The extent to which this regulatory action of the vasa vasorum may be
      comprised by raised venous pressure and venous distension has not been defined.

PMID- 8984143
TI  - [Morphology and vascularization of the varicose internal saphenous vein.
      Comparison with the normal structure].
AB  - After reviewing the main characteristics of the normal long saphenous vein, the
      histological alterations observed in varicose veins are described. Samples were
      obtained from 14 patients undergoing venous surgery for varicose veins with long
      saphenous vein incompetence. These alterations mostly involve the connective
      tissue prolife-rating in the middle layer and causing the separation and
      interruption of the muscular bundles. In addition, the vasa vasorum network
      through the venous wall was investigated. These vessels were normally observed in
      the adventitial layer and the outer third of the media. In some samples from
      varicose veins, vasa vasorum were increased and capillaries close to the intimal
      layer.

PMID- 8984142
TI  - [Vascularization of the wall of the superficial veins. Anatomic study of the vasa
      vasorum].
AB  - INTRODUCTION: The blood vessel wall is almost always nourished by two ways; from
      the blood stream itself and through the outer part of the wall by vasa vasorum.
      AIM OF THE STUDY: The aim of this study was to demonstrate that this kind of
      nutrition is also available for the venous wall and to define the distribution
      pattern in superficial venous walls. MATERIALS AND METHODS: 50 long saphenous
      veins and 20 short saphenous veins latex or barium injections, dissections with
      magnifying glasses and microradiographies. Topographical evaluation of the origin
      of vasa vasorum. RESULTS: The results showed that vasa vasorum originated from
      perforating arteries coming from several levels and getting a lot of anastomosis.
      We showed that the main sources for the long saphenous vein are the external
      pudendal artery and descending artery of the knee and for the short saphenous
      vein, the short saphenous vein artery. In thrombosis and varicose veins, the vasa
      were strongly altered. CONCLUSION: This study outlines the fact that superficial
      veins are supplied by arterial and venous vasa vasorum, and the role of vasa
      vasorum must be considered when questioning the pathogenesis of varicose and post
      thrombotic disease.

PMID- 8984144
TI  - [Laser-doppler flowmetry in vivo and reactivity of the normal and abnormal venous
      wall].
AB  - Venous wall flux was measured using laser-Doppler flowmetry on the external
      surface of 24 normal veins, partially dissected during the preparation of the
      vein for aortocoronary bypass grafting. Measurements were performed before the
      final dissection of the vein when at least 3/4 of the adventitia and
      periadventitia tissue was still intact for a length of 3 cm. The segment of vein
      (10 cm) proximal to the sapheno-femoral junction was studied. Measurements were
      repeated on 22 varicose veins before stripping or ligation of the sapheno-femoral
      junction. Flux was measured with a Laserflo (Vasamedics) flowmeter. A Delrin
      (polycarbonate) spacer was placed between the probe and the vein wall surface.
      Measurements shown are the average of three minutes recording. Preliminary
      analysis indicates that flux appears to be lower in varicose veins in comparison
      with flux in the normal vein wall. However the variability of results and
      technical problems in flux measurements indicate the need of a larger measurement
      sample before confirming the observation of a decreased perfusion of the varicose
      venous wall.

PMID- 8984145
TI  - [Measurement of oxygen tension in normal and varicose vein walls].
AB  - Oxygen tension (PO2) was investigated in vivo in the long saphenous vein from 21
      varicose patients (31 veins) during venous surgery and 7 patients with normal
      venous network undergoing popliteo-femoral by-pass. Measurement was achieved
      using computerized polarographic system Kimoc 6650 (Eppendorf, Hamburg) providing
      a microdriven stepwise progression of a needle probe. Oxygen tension profile was
      similar in both groups of patients. A slow PO2 decrease was observed from
      adventitia up to the union of the middle and inner thirds of the media where
      values were at the lowest then followed by a marked increased in the intima and
      the saphenous lumen. Oxygenation of the two external thirds of the venous wall
      was provided by vasa vasorum. The average minimum values in the media was
      significantly reduced in varicose veins compared to no-varicose veins (7,9 mmHg
      versus 13,4 mmHg; p < 0,05). These results indicated the key role of vasa vasorum
      flux in the long saphenous vein nutrition and suggest a primary or secondary
      deficiency in oxygen supply in varicose veins.

PMID- 8984146
TI  - [The vasa vasorum of the arteries].
AB  - Nourishment of arteries is accomplished by diffusion from the lumen of the vessel
      and from vasa vasorum. Most normal arteries have an extensive network of vasa in
      the adventitia that arise from branch points of parent arteries. When the
      thickness of arteries exceeds the ability of simple diffusion of nutrients from
      the lumen (larger muscular of atherosclerotic arteries), vasa extend into the
      media and intima. Vasa in the intima-media arise predominantly from adventitial
      vasa, but can arise from the lumen in vascular grafts and recanalized arteries
      after thrombosis. Vasa respond to vasoactive stimuli, and can regress after they
      vascularize arterial grafts and in response to regression of the atherosclerotic
      lesions. Therefore, vasa can increase blood flow to the artery wall by dilation
      of existing arteries or by formation of new vessels (neovascularization).
      Conversely, vasa can reduce blood flow to the artery wall by active constriction
      or by regression (involution) of existing vasa. The pathophysiological
      significance of vasa vasorum in normal and diseased arteries is related to their
      structure. Vasa in the intima-media are thin-walled endothelial cell tubes with
      thin or absent medial smooth muscle cells. Therefore, they are prone to collapse
      and rupture in response to arterial pressure, mechanical forces in the artery,
      necrotic substances found in diseased arteries, and vasospasm. Vasa also provide
      the artery with a vast absorptive endothelial surface that may have important
      implications for arterial lipid kinetics, and delivery and removal of
      neurohumoral agents from the artery wall. These properties have lead to
      speculation about their role in the pathogenesis of atherosclerosis, plaque
      rupture and thrombosis, medial ischemia leading to arterial dissection and
      aneurysm, restenosis after angioplasty, and post-stenotic dilatation. Finally,
      larger veins also have an extensive network of vasa that have been implicated in
      the pathogenesis of venous thrombosis and varicose veins.

PMID- 8984147
TI  - [Transport and localization of troxerutin in the venous wall].
AB  - The vein wall is nourished by diffusion of blood nutrients from the lumen and
      from the vasa vasorum. It is likely that drugs take the same ways to reach and
      diffuse through the vessel wall. Thus the uptake of a drug with affinity for the
      vein wall should give information on its transport to the tissue. This study
      aimed to explore troxerutin uptake by the long saphenous vein. Troxerutin is a
      naturally fluorescent flavonoid which has been known to improve subjective signs
      of patients with chronic venous insufficiency. Nine patients undergoing surgical
      treatment of varicosis were enrolled in the study. They received for the last 4
      days before surgery either 3,500 mg of troxerutin (n = 4) or 1,000 mg twice daily
      (n = 2). Three patients as controls did not receive any drug. Two samples from
      thigh and calf long saphenous vein were harvested in each patients and
      investigated with a confocal laser scanning microscope developed by our institute
      measuring the fluorescence emitted by troxerutin after excitation by a 458 nm
      wavelength laser-beam. The intensity of the overall fluorescence was
      significantly higher in the treated groups (p < 0,001) and slightly higher in the
      patient who received 3,500 mg of troxerutin than with the lower dosage. The outer
      wall region provided the highest fluorescence in the treated group while a
      significant difference was observed in the fluorescence of the medial region
      between treated and control group. These results showed a marked affinity of
      troxerutin for the venous wall. The highest uptake in the outer wall region is
      likely to result from transport through vasa vasorum, owing to the rheologic
      properties of the drug. The significant medial fluorescence may account for the
      venous tone improvement with the drug.

PMID- 8984148
TI  - Cytotoxic oxygenated desmosterols of the red alga Galaxaura marginata.
AB  - Desmosterol (1), 24,25-epoxycholesterol (2), 24-hydroperoxycholesta-5,25-dien-3
      beta-ol (3), 25-hydroperoxycholesta-5,23(E)-dien-3 beta-ol (4), cholesta-5,25
      diene-3 beta,24-diol (5), and 24,25-epoxy-6 beta-hydroxycholest-4-en-3-one (7)
      were isolated from the marine red alga Galaxaura marginata; sterols 3, 4, and 7
      were isolated for the first time from a natural source. Sterols 3-7 exhibited
      significant cytotoxicity toward several cancer cell lines.

PMID- 8984149
TI  - Amarogentin, a naturally occurring secoiridoid glycoside and a newly recognized
      inhibitor of topoisomerase I from Leishmania donovani.
AB  - A MeOH extract of Swertia chirata found to inhibit the catalytic activity of
      topoisomerase I of Leishmania donovani was subjected to fractionation to yield
      three secoiridoid glycosides: amarogentin (1), amaroswerin (2), and sweroside
      (3). Amarogentin is a potent inhibitor of type I DNA topoisomerase from
      Leishmania and exerts its effect by interaction with the enzyme, preventing
      binary complex formation.

PMID- 8984150
TI  - Novel marine di-Z-carotenoids: cucumariaxanthins A, B, and C from the sea
      cucumber Cucumaria japonica.
AB  - The novel marine carotenoids, cucumariaxanthins A (1), B (2), and C (3), were
      isolated from the northern sea cucumber Cucumaria japonica. Their structures and
      absolute stereochemistries were determined to be (5S,6S,5'S,6'S)-(9Z,9'Z)
      5,6,5',6'-tetrahydro-beta,beta- carotene-4,4'-dione for 1; (5S,6S,4'S,5'S,6'S)
      (9Z,9'Z)-4'-hydroxy-5,6,5',6'-tetrahydro-beta, beta- caroten-4-one for 2; and
      (4S,5S,6S,4'S,5'S,6'S)-(9Z,9'Z)-5,6,5',6'-tetrahydro-beta,beta-car otene-4,4'-
      diol for 3 by extensive spectroscopic analysis and by the modified Mosher's
      method. Cucumariaxanthin C showed an inhibitory effect on Epstein-Barr virus
      activation in a short-term in vitro assay.

PMID- 8984152
TI  - Pyridine monoterpene alkaloid formation from iridoid glycosides. A novel PMTA
      dimer from geniposide.
AB  - New pyridine monoterpene alkaloids (PMTAs) have been synthesized from the iridoid
      glycosides 8-epi-loganin, cornin, and antirrinoside by treatment with beta
      glucosidase and aqueous NH4-OAc. The PMTA from antirrinoside contained an 8-alpha
      OAc group from the opened 7,8-epoxide moiety. Treatment of genipin, the aglycone
      of geniposide, with HCl(g) and NH3(g) yielded the PMTA racemigerine, a known
      plant isolate, in which the C=C-CH2OH side chain was converted to C=C-CH3.
      Reaction of geniposide with beta-glucosidase and aqueous NH4OAc led to oligomeric
      alkaloids, but at high dilution a dimer was obtained whose structure was formally
      that of a Diels-Alder adduct between racemigerine and a dihydropyridine. These
      biomimetic semisyntheses were analyzed in terms of reaction mechanisms and the
      relative paucity of known plant PMTAs in comparison with the multitudinous
      occurrence of their presumed iridoid glycoside precursors.

PMID- 8984151
TI  - Bicinchoninic acid protein assay in the determination of adriamycin cytotoxicity
      modulated by the MDR glycoprotein.
AB  - The development of simultaneous resistance to structurally unrelated drugs in
      cancer cells is a major obstacle to effective cancer chemotherapy. This multidrug
      resistance (MDR) phenomenon is largely attributed to overexpression of a 170 kD
      glycoprotein, which serves as a transmembrane efflux pump in extruding a variety
      of natural anticancer drugs such as vinblastine, doxorubicin, and taxol from
      cancer cells. It is desirable, therefore, to discover compounds that can block
      the efflux mechanism and thus reverse drug resistance. The bicinchoninic acid
      protein assay has been adapted for use in a microtiter plate, into an easy,
      indirect method for screening MDR efflux blockers in plant extracts. This
      spectrophotometric assay is used to determine the enhancement of adriamycin
      cytotoxicity against resistant cancer cells by plant extracts or pure compounds
      indirectly. We have shown that the optical density measured (amount of cellular
      protein present) correlates with the number of viable cells and that fluorescence
      of Adriamycin associated with the cell correlates with the concentrations of
      Adriamycin added to the media. In addition, the relative efficacy of MDR reversal
      by various alkaloids has been determined.

PMID- 8984153
TI  - The volatile oil composition of fresh and air-dried buds of Cannabis sativa.
AB  - The composition of the steam-distilled volatile oil of fresh and air-dried,
      indoor-grown marijuana was studied by GC/FID and GC/MS. In all, 68 components
      were detected of which 57 were fully identified. Drying of the plant material had
      no effect on the qualitative composition of the oil and did not affect the
      ability of individuals familiar with marijuana smell to recognize the odor.

PMID- 8984154
TI  - Molecular structure of terrecyclodiol: a derivative of the antifungal metabolite
      terrecyclic acid A from Aspergillus terreus.
AB  - A strain of Aspergillus terreus, which was isolated from organic mulch and
      inhibited the growth of the plant pathogen Phytophthora cinnamomi, produces an
      antifungal metabolite when grown in liquid culture. This metabolite was isolated
      by bioassay-guided fractionation and identified as terrecyclic acid A (1). X-ray
      diffraction studies and spectroscopic details of the derived terrecyclodiol (2)
      are described.

PMID- 8984155
TI  - Chlorochimaphilin: a new antibiotic from Moneses uniflora.
AB  - A study of the antimicrobial compounds from Moneses uniflora resulted in the
      isolation of a novel compound, 8-chloro-2,7-dimethyl-1,4-naphthoquinone (8
      chlorochimaphilin) (1), together with chimaphilin (2) and 3-hydroxychimaphilin
      (3) as the antimicrobial components. 2,7-Dimethyl-1,3-dihydroxynaphthyl 4-O-alpha
      L-rhamnopyranoside (4) and 2,7-dimethoxy-1,4,8-trihydroxynaphthalene (6) were
      also isolated and identified.

PMID- 8984156
TI  - A new quassinoid from Castela texana.
AB  - A new quassinoid, 11-O-trans-p-coumaroyl amarolide (1) was isolated from Castela
      texana, and the structure was elucidated by spectroscopic analysis. Compound 1 is
      the first coumaroyl quassinoid derivative to have been isolated from nature. The
      known compounds amarolide (2), chaparrinone, chaparrin, glaucarubolone,
      holacanthone, and 15-O-beta-D-glucopyranosyl glaucarubol were also isolated. All
      isolated compounds were tested for their cytotoxicity and antiprotozoal
      activities.

PMID- 8984158
TI  - Calcium spirulan, an inhibitor of enveloped virus replication, from a blue-green
      alga Spirulina platensis.
AB  - Bioactivity-directed fractionation of a hot H2O extract from a blue-green alga
      Spirulina platensis led to the isolation of a novel sulfated polysaccharide named
      calcium spirulan (Ca-SP) as an antiviral principle. This polysaccharide was
      composed of rhamnose, ribose, mannose, fructose, galactose, xylose, glucose,
      glucuronic acid, galacturonic acid, sulfate, and calcium. Ca-SP was found to
      inhibit the replication of several enveloped viruses, including Herpes simplex
      virus type 1, human cytomegalovirus, measles virus, mumps virus, influenza A
      virus, and HIV-1. It was revealed that Ca-SP selectively inhibited the
      penetration of virus into host cells. Retention of molecular conformation by
      chelation of calcium ion with sulfate groups was suggested to be indispensable to
      its antiviral effect.

PMID- 8984159
TI  - Vasculyne, a new cytotoxic acetylenic alcohol from the marine sponge
      Cribrochalina vasculum.
AB  - A new C43 acetylenic alcohol, vasculyne (1), was isolated by cytotoxicity-guided
      fractionation of the Caribbean sponge Cribrochalina vasculum. The structure of 1
      was determined by spectroscopic methods.

PMID- 8984160
TI  - Oscillapeptin G, a tyrosinase inhibitor from toxic Oscillatoria agardhii.
AB  - Oscillapeptin G, a tyrosinase inhibitor, was isolated from the freshwater toxic
      cyanobacterium Oscillatoria agardhii. The structure was determined to be 1 by
      chemical degradation and 2D NMR analyses.

PMID- 8984161
TI  - New cytotoxic briaran diterpenes from the Formosan gorgonian Briareum sp.

PMID- 8984163
TI  - Isolation of guaianoid pigments from the gorgonian Calicogorgia granulosa.
AB  - Three pigments of the guaiazulene class have been isolated from the gorgonian
      Calicogorgia granulosa. Structures of these compounds have been determined as
      guaiazulene, 2,2'- diguaiazulenylmethane, and a new compound, 2,2'
      biguaiazulenyl, by combined chemical and spectroscopic methods. 2,2'
      Biguaiazulenyl exhibited moderate antimicrobial activity.

PMID- 8984162
TI  - Two fungal lanostane derivatives as phospholipase A2 inhibitors.
AB  - The hydroalcoholic extract of Poria cocos and two lanostane derivatives isolated
      from it, pachymic acid (1) and dehydrotumulosic acid (2), were active as
      inhibitors of phospholipase A2 from snake venom when a polarographic method was
      used. Dehydrotumulosic acid exhibited an IC50 of 0.845 mM. These two compounds
      are structurally related to certain triterpenoids from Ganoderma and Schinus that
      have previously been described as competitive inhibitors of phospholipase A2.
      These comprise a new group of natural potential antiinflammatory agents due to
      their interaction with that enzyme.

PMID- 8984164
TI  - Beset by buzzwords.

PMID- 8984165
TI  - Health care of Oklahoma Indians.
AB  - The many unique aspects of Indian life extend into the health care arena, of
      special interest in Oklahoma, the "home of the red man." The long historical
      relationship of certain Indian tribes with the federal government has resulted in
      one of the most complicated social, administrative, and governmental arrangements
      anywhere. A consequence of this relationship was, in effect, a business
      transaction resulting in the ceding of virtually all Indian lands of the U.S. and
      an assumption by the latter to provide certain services, including health care,
      to affected tribes. With the 33 different tribes in Oklahoma; the dual
      entitlement possessed by Indian people; the contributions of the Indian Health
      Service to the economy of Oklahoma; and the growing revolution in health care,
      knowledge of the special circumstances of Indian life and health care is
      important even for practitioners who do not regularly encounter Indian people in
      their own practices.

PMID- 8984157
TI  - Caparratriene, an active sesquiterpene hydrocarbon from Ocotea caparrapi.
AB  - Caparratriene (1), a new sesquiterpene hydrocarbon with significant growth
      inhibitory activity (IC50 = 3.0 +/- 0.5 x 10(-6) M) against CEM leukemia cells,
      was isolated from the oil of Ocotea caparrapi (Nates) Dugand. The structure of 1,
      determined by spectroscopic techniques, corresponded to (E,E)-3,7,11-trimethyl
      2,4,10-dodecatriene (C15H26).

PMID- 8984166
TI  - Poison prevention for the elderly.
AB  - Persons 60 years of age or older accounted for only about 3% of poison-center
      related calls. However, this age group comprised more than 20% of poison-center
      reported poisoning deaths in 1994. The physiological changes associated with the
      aging process that frequently alter the overall effects of a drug (or a poison)
      make this rapidly growing population group especially susceptible to both acute
      and chronic toxicity. The prevention of intentional and unintentional poisonings
      and misdosing of medications among the elderly requires new and imaginative
      approaches.

PMID- 8984167
TI  - Oklahoma Centralized Verification Organization: a way out of the paperwork
      nightmare.

PMID- 8984168
TI  - Osteoporosis: it is a fact of life but both preventable and treatable.

PMID- 8984169
TI  - Chlamydia trachomatis is too costly to ignore.

PMID- 8984170
TI  - Zona Pellucida Glycoproteins and Immunocontraception. Proceedings of the
      International Symposium. New Delhi, India, 2-5 December 1995.

PMID- 8984171
TI  - Molecular genetics of the zona pellucida: implications for immunocontraceptive
      strategies.
AB  - Successful immunocontraceptive agents must prevent fertilization without
      compromising the health of the individual exposed to immunization. The zona
      pellucida, which surrounds all mammalian eggs and is unique to the female gamete,
      represents a potential target for immunocontraception. Mouse and human zonae
      pellucidae are composed of three glycoproteins, designated ZP1, ZP2 and ZP3. The
      genes are conserved and the transcripts that encode the zona proteins have been
      characterized in both species. In mice, the expression of the zona genes is
      oocyte specific. The recent elucidation of the primary structure of the zona
      proteins in a number of species has provided critical information for the
      rational design of a contraceptive vaccine. We and others have demonstrated that
      both passive and active immunization strategies that target individual zona
      proteins can prevent fertilization. Although various contraceptive strategies
      have been tested in a laboratory setting, the applicability of these protocols to
      humans remains to be determined. The recent revolution in transgenesis coupled
      with the cloning of the human zona pellucida genes provide the means to produce
      animal models for testing immunocontraceptive strategies that target human zona
      proteins. These models could provide a system for the initial evaluation of
      vaccine candidates prior to trials in primates.

PMID- 8984172
TI  - Follicular maturation and atresia--possible role of intraovarian regulatory
      factors.
AB  - In addition to the gonadotrophins, factors known to be present or produced within
      the ovary are also involved in the regulation of follicular development and
      atresia. One such modulator of ovarian function is the prorenin-renin-angiotensin
      system (PRAS) which seems to be associated with atresia. Although it is primarily
      under gonadotrophic control, the expression of the ovarian PRAS is also shown
      here to be subject to modulation by intraovarian factors. Addition of granulosa
      cell conditioned medium to bovine theca cells inhibited the LH-stimulated
      prorenin secretion in a dose-dependent manner, which leads to the assumption that
      granulosa cells secrete a factor(s) that, even in the presence of LH, keeps
      prorenin secretion low. Since growth factors and cytokines are known to be
      produced by granulosa cells, we have evaluated the effects of tumour necrosis
      factor alpha, basic fibroblast growth factor and transforming growth factor alpha
      on the LH- and 8Br-cAMP-induced prorenin secretion, and observed that all
      agonists inhibited the LH- and 8Br-cAMP-stimulated prorenin secretion in a dose
      dependent manner. In contrast, addition of transforming growth factor beta, a
      secretory product of theca cells, further augmented gonadotrophin-induced
      prorenin synthesis. In conclusion, we assume that in the presence of healthy
      granulosa cells, suppression of the ovarian PRAS by granulosa cell derived
      factors may prevent a follicle from undergoing atresia, whereas in the presence
      of atretic granulosa cells, theca cell derived factors may enhance the expression
      of the PRAS, resulting in follicular atresia.

PMID- 8984173
TI  - In vitro maturation of buffalo oocytes: role of insulin and its interaction with
      gonadotrophins.
AB  - A variety of signals is involved in the acquisition of competence to resume
      meiosis in buffalo oocytes. There is evidence that gonadotrophins are required
      for the resumption of meiosis and to achieve developmental competence. However,
      the source of the serum supplement also influences maturation of buffalo oocytes.
      Fetal calf serum was more effective at achieving maturational competence compared
      with oestrous serum. All the changes were found to be supported and strictly
      regulated by the somatic cells of the follicle. Further studies revealed that a
      variety of ovarian autocrine and paracrine factors may modulate the maturation of
      buffalo oocytes. The role of growth factors, particularly insulin, in in vitro
      maturation and granulosa cell differentiation is discussed.

PMID- 8984174
TI  - Assisted hatching in an in vitro fertilization programme.
AB  - Assisted hatching was performed on 37 women (IVF, n = 12; micromanipulation, n =
      25), who were at risk of poor implantation after in vitro fertilization and
      micromanipulation, and who had previous cycles of failed implantation. A total of
      292 oocytes was retrieved (7.9 per cycle) of which 90 were subjected to IVF and
      202 were micromanipulated. Assisted hatching was performed on day 3 of culture,
      on six- to eight-cell embryos, by the technique of mechanical partial zona
      dissection. All the patients undergoing the procedure of assisted hatching had
      embryos with thick zonae, greater than 15 microns. Assisted hatching was
      performed on 39 embryos (55.7%) in the IVF group and 104 embryos (77.6%) in the
      micromanipulation group. The damage rate after hatching was 1.4%. The pregnancy
      rate per cycle was 50% in the IVF group and 44% in the micromanipulation group,
      compared with 10% (IVF) and 19.2% (micromanipulation) in the control groups.
      Assisted hatching, by partial zona dissection, results in significant improvement
      in pregnancy rates in women more than 38 years of age, who have a thick zona and
      with previous poor implantation results. This paper reports the first pregnancy
      in India by the technique of assisted hatching (partial zona dissection).

PMID- 8984176
TI  - Studies on the epitope of pig zona pellucida recognized by a fertilization
      blocking monoclonal antibody.
AB  - Heat solubilized pig zona pellucida (pZP) was separated into four major
      glycoprotein families (pZP1, pZP2, pZP3, pZP4). Cloning of a full-length cDNA
      coding for pZP1 revealed that the coding sequence for pZP4 was immediately
      followed by the sequence for the amino-terminal residue of pZP2 and that they
      shared a significant similarity with mouse and human ZP2, which are considered to
      serve as a secondary sperm receptor in sperm-zona interactions. One of the
      monoclonal antibodies, mAb-5H4, produced against pZP4 inhibited the binding of
      boar and human spermatozoa to each of the homologous oocytes. The epitope
      recognized by mAb-5H4 was determined to be present on a 10 amino acid sequence of
      pZP1(50-59) by using epitope mapping and analysis of chain flexibility of pZP4. A
      synthetic 18mer peptide corresponding to pZP1(50-67) reacted with mAb-5H4, and
      mouse antisera raised to the synthetic 18mer peptide recognized intact pig zona
      pellucida and strongly inhibited the fertilization of pig oocytes with boar
      spermatozoa in vitro. These results suggest that the pZP4 peptide (50-59)
      identified as an epitope for mAb-5H4 could be a promising candidate in the
      development of a contraceptive vaccine.

PMID- 8984175
TI  - Strategies for designing an immunocontraceptive vaccine based on zona pellucida
      synthetic peptides and recombinant antigen.
AB  - Immunization of female bonnet monkeys (Macaca radiata) with pig zona pellucida
      glycoprotein ZP3 using adjuvants permissible for human use leads to infertility.
      Fifty per cent of the animals conceived after antibody titres declined. Animals
      that failed to regain their fertility did not show any obvious ovarian changes.
      As part of the attempt to design an effective immunocontraceptive vaccine based
      on synthetic peptides, the epitopes recognized by monoclonal antibodies (mAb)
      against pig ZP3 alpha and ZP3 beta and possessing contraceptive efficacy in vitro
      were mapped. These studies identified an N-blocked decapeptide from the N
      terminus corresponding to 23-32 amino acids of the precursor protein of pig ZP3
      beta. As an alternative approach to using synthetic peptides, DNA encoding bonnet
      monkey ZP3 was cloned and sequenced. The deduced primary amino acid sequence
      revealed an overall similarity of 93.9% with human ZP3. Bonnet monkey ZP3
      corresponding to an internal 975 nucleotide fragment excluding the N-terminus
      signal sequence and the C-terminus transmembrane domain has been expressed in
      Escherichia coli. These results will assist in the design of an
      immunocontraceptive vaccine based on either synthetic peptides or recombinant
      glycoproteins or proteins corresponding to ZP.

PMID- 8984177
TI  - Molecular biology approaches to evaluate species variation in immunogenicity and
      antigenicity of zona pellucida proteins.
AB  - Immunocontraception using the glycoproteins of the mammalian zona pellucida (ZP)
      has held great promise because antibodies specific to ZP antigens would inhibit
      fertility and not be abortive. It has been shown, however, that some ZP proteins
      will elicit adverse effects since immunization may affect ovarian follicular
      development. These effects vary among different mammalian species as well as on
      the source of the ZP immunogen. Therefore, the use of molecular biology has been
      essential in identifying specific ZP protein(s) that inhibit fertility without
      altering ovarian follicular development and in defining the relationships of ZP
      proteins among different species. Use of recombinant ZP proteins has allowed us
      to begin to dissect antigenic domains of ZP proteins and to evaluate their
      potential roles in the fertilization process. Recent studies using recombinant
      rabbit ZP proteins to immunize cynomolgus monkeys (Macaca fascicularis) have
      shown that the 55 kDa ZP protein will elicit antibodies that inhibit sperm
      binding while not altering ovarian function, in contrast to immunization with a
      recombinant truncated protein of the 75 kDa ZP protein which causes ovarian
      dysgenesis. The rabbit 55 kDa protein is the homologue of the pig ZP3 alpha sperm
      receptor and the human ZPB protein but is distinct from the mouse ZP3 sperm
      receptor. Expression of this protein using the baculovirus expression system has
      further shown that the 55 kDa protein binds to capacitated rabbit spermatozoa
      over the acrosomal region and induces the acrosome reaction. Antibodies against
      this recombinant form of the ZP also inhibit rabbit spermatozoa from binding to
      rabbit egg in vitro. These studies demonstrate the need to determine the
      structure and function of ZP proteins of different mammalian species to evaluate
      their potential for contraceptive vaccines.

PMID- 8984178
TI  - Immunogenicity of zona pellucida vaccines.
AB  - Development of zona pellucida (ZP) based contraceptive vaccines raises a number
      of complications that challenge current immunological capabilities. Our research
      examines two aspects of these immunological problems. First, recent studies
      demonstrate that one bacterially expressed rabbit ZP recombinant vaccine (rec55)
      induces autoantibodies in primates that prevent sperm-ZP binding and induction of
      the acrosome reaction in the homologous ZP in vitro. Immunization with rec55 does
      not induce ovarian pathology, and the duration of antibody titres indicates that
      this vaccine would have reversible effects on fertility. However, the
      immunogenicity of the rec55 protein produced in the pEX bacterial expression
      vector is low. We have therefore expressed the cDNA encoding rec55 using the pGEX
      vector for the following reasons: (i) the pGEX expressed recombinant proteins are
      soluble in aqueous solution; (ii) affinity purification of recombinant proteins
      on glutathione Sepharose columns is more effective for obtaining larger
      quantities of purified protein; and (iii) the availability of protease cleavage
      sites between the ZP and glutathione S transferase fusion proteins should
      eliminate the possibility of carrier-mediated suppression of immune responses.
      These improvements in protein production and purification yield immunogen which
      is more malleable to immunological studies. Second, while it is clear that ZP
      recombinant vaccines can eliminate the problem of ovarian pathology, it is
      important to understand how such pathology results from immunization with native
      ZP proteins and certain recombinant ZP proteins. To this end, we have initiated
      immunization studies in baboons comparing rabbit ZP and pig ZP immunogens in
      Titremax adjuvant. Unilateral ovariectomies at different time points after
      immunization (1.5, 2, 4 and 6 months) will allow studies on the time course of
      pathology within the ovary. Comparison of these results with ongoing rabbit ZP
      immunizations will help elucidate the differences in immunogenicity of ZP
      proteins isolated from the two species.

PMID- 8984179
TI  - Influence of autoimmune ovarian disease pathogenesis on ZP3 contraceptive vaccine
      design.
AB  - Zona pellucida (ZP) glycoproteins possess sperm receptor-binding activities.
      Antibodies against ZP can block sperm-egg interaction and thereby prevent
      fertilization. The feasibility of developing a safe contraceptive vaccine based
      on the ZP has been hampered by the finding that active immunization with
      autologous or heterologous ZP proteins results in infertility that is associated
      with ovarian dysfunction. A mouse model was used to investigate mechanisms of the
      ovarian pathology that is induced by active immunization with a 13mer peptide
      derived from mouse ZP3 (mZP3(330-342)). This peptide includes one native B-cell
      epitope and two nested T-cell epitopes. Ovarian pathology could be transferred
      into naive recipients by CD4+ T cells, but not by antibodies, from immunized
      mice, suggesting the importance of T cells in the mechanism of ovarian
      pathogenesis. Moreover, immune responses, as well as disease induction, were
      restricted to H-2a,k,u,s,axb haplotypes. On the basis of this mouse model, a
      strategy to generate a contraceptive anti-ZP antibody response without a
      pathogenic T-cell response, irrespective of H-2 haplotype, is described. The B
      cell epitope was modified by amino acid substitution to eliminate the overlapping
      oophoritogenic T-cell epitope, and was linked to a promiscuous foreign T-cell
      epitope, bovine RNase94-104. The resultant chimaeric peptide (CP2) induced anti
      ZP antibodies in 100% of the eight strains of inbred mice with different H-2
      haplotypes without significant disease induction. An antifertility trial in B6AF1
      female mice immunized with CP2 showed that the anti-ZP antibody was associated
      with a reduction in fertility. This infertility was reversed with a decline in
      anti-ZP antibody titre. Preliminary data show that this strategy of vaccine
      design may also be applied to primates.

PMID- 8984180
TI  - Primate response to immunization with a homologous zona pellucida peptide.
AB  - Development of a contraceptive vaccine using zona pellucida (ZP) antigens has
      been hampered by the observation that the immune response to the antigens results
      in altered ovarian function and depletion of the follicular pool of oocytes. The
      amino acid sequences of many ZP proteins have been determined in the past decade
      allowing study of fully synthetic peptide immunogens based on these ZP sequences.
      Such immunogens permit a precisely targeted response. The non-human primate is
      the best model for predicting how women may respond to ZP peptide vaccines.
      Cynomolgus macaques (Macaca fascicularis) have been immunized with synthetic
      peptides comprising a human ZP3 epitope and a macaque homologue of the same
      epitope. In both studies, immune response to the peptides was initiated, and
      infertility was accompanied by normal ovarian function.

PMID- 8984181
TI  - Evaluation of zona pellucida antigens as potential candidates for
      immunocontraception.
AB  - Antibodies directed against the zona pellucida can interrupt sperm-egg
      recognition in vitro. However, the mechanisms by which anti-zona antibodies exert
      this contraceptive effect in vivo remain uncertain. There is an accumulating body
      of evidence to suggest that active immunity against zona antigens not only
      induces infertility via an antibody-mediated interruption of sperm--egg
      interaction but also disrupts normal ovarian function. We have evaluated the
      consequence of inducing active immunity against purified recombinant human ZP3
      (rec.hZP3) and human ZP3 peptides, using the marmoset monkey, Callithrix jacchus,
      as an animal model. Although infertility was established in animals that received
      rec.hZP3, it was associated with ovarian dysfunction characterized by suppression
      of folliculogenesis and depletion of the primordial follicle pool. Immunization
      with continuous human ZP3 peptides, identified by epitope mapping studies, did
      not induce ovarian pathology but the antibody titres were insufficient to
      suppress fertility significantly and consistently. Clearly, further research is
      required to identify and segregate epitopes on the zona glycoproteins that are
      capable of inducing infertility without any side effects.

PMID- 8984183
TI  - Genomic organization of the gene for pig zona pellucida glycoprotein ZP1 and its
      expression in mammalian cells.
AB  - The pig zona pellucida (pZP) is composed of glycoproteins pZP1, pZP3 alpha and
      pZP3 beta. Previously, we showed that pZP1 was proteolytically cleaved into two
      components (pZP4 and pZP2), and suggested that pZP1 was a homologue of mouse ZP2.
      We now report the genomic organization of pZP1 gene, and expression of the
      recombinant protein in mammalian cells. Two genomic clones, pZP4g and pZP4.1,
      were isolated by screening the pig genomic library with an already cloned cDNA
      encoding pZP4 as a probe. These clones covered 25 kb of the genome, including the
      entire pZP1 locus. The pig ZP1 genome consists of 18 exons and 17 introns. For
      production of the recombinant proteins of pZP1, a minigene containing a genomic
      fragment covering exon 6 to exon 17 was constructed and cloned into the
      expression vector, pBCMGS-neo. Mammalian cell lines, CHO (for stable expression)
      and 293T (for transient expression), transfected with the plasmid construct
      synthesized pZP1 recombinant proteins, probably as a membrane-bound protein.

PMID- 8984182
TI  - Applications of pig zona pellucida immunocontraception to wildlife fertility
      control.
AB  - A unique application of pig zona pellucida (PZP) immunocontraception is the
      control of wildlife populations. A native PZP vaccine has been successfully
      applied to wild horse and donkey populations. A single annual booster inoculation
      was capable of maintaining contraception. Seven consecutive years of PZP
      treatment in wild mares resulted in no detectable debilitating side effects, and
      reversibility of contraception has been documented among mares treated for up to
      4 consecutive years. Long-term treatment (5-7 years) is associated with some
      ovulation failure and depressed urinary oestrogen concentrations. Complex social
      behaviours in horses were unaffected by treatment. PZP immunocontraception has
      also been successfully applied to white-tailed deer, with no detectable changes
      in ovarian histology after 2 years of treatment. Seventy-four species of captive
      zoo animals have been treated with the PZP vaccine, with documented success in 27
      species, including members of the orders Perissodactyla (Equidae), Artiodactyla
      (Cervidae, Capridae, Giraffidae, Bovidae), and Carnivora (Ursidae, Mustelidae,
      Felidae). Immunocytochemistry studies have demonstrated a high degree of
      crossreactivity between anti-PZP antibodies and African elephant zona pellucida.
      The need for a one-inoculation form of the vaccine has led to the incorporation
      of PZP into lactide-glycolide microspheres, which cause a delayed release of the
      PZP. PZP immunocontraception of wildlife has potential because of (1) > 90%
      effectiveness, (2) the ability for remote delivery, via darts, (3) reversibility
      after short-term use, (4) a wide breadth of effectiveness across many species,
      (5) a lack of debilitating side-effects even after long-term treatment, and (6)
      minimal effects upon social behaviours.

PMID- 8984184
TI  - Highlights of the symposium.

PMID- 8984185
TI  - Structure and function of the N-linked carbohydrate chains of pig zona pellucida
      glycoproteins.
AB  - The N-linked carbohydrate chain of the PZP3 glycoprotein family of pig zona
      pellucida is shown by competition assay to possess sperm receptor activity.
      Structural analysis reveals that the N-linked chains comprise neutral and acidic
      complex-type chains. The tri- or tetra-antennary fraction in the neutral chains
      possesses the sperm receptor activity, but the activity is markedly reduced
      compared with that of PZP3, suggesting that the protein moiety participates in
      the maintenance of proper orientation of the active chain. Two components in the
      PZP3 family can be separated by reverse-phase HPLC after endo-beta-galactosidase
      (E beta G) digestion and one of the digests, E beta G-PZP3 alpha, possesses the
      sperm receptor activity. E beta G-PZP3 alpha deprived of O-linked chains by
      treatment with alkali retains the activity comparable with E beta G-PZP3 alpha,
      while E beta G-PZP3 alpha deprived of N-linked chains by N-glycanase digestion
      loses the activity. Furthermore, competition assay of the digests of E beta G
      PZP3 alpha with lysyl-endopeptidase indicates that the active chain is linked to
      Asn67 or Asn84 of PZP3 alpha or to both residues. We conclude that sperm-egg
      binding in pigs is mainly mediated by tri- or tetra-antennary, neutral, complex
      type N-linked carbohydrate chain(s) localized in the N-terminal region of PZP3
      alpha protein.

PMID- 8984186
TI  - The expression and localization of zona pellucida glycoproteins and mRNA in
      cynomolgus monkeys (Macaca fascicularis).
AB  - The zona pellucida (ZP) is an extracellular matrix composed of multiple
      glycoproteins that surrounds all mammalian oocytes. Analysis of the genes
      encoding the ZP proteins indicates that there are three classes ZPA (largest),
      ZPB (intermediate) and ZPC (smallest). Polyclonal antibodies developed against
      recombinant proteins of human and pig ZP have been used to identify
      immunohistochemically the components of the ZP of cynomolgus monkeys during the
      course of follicular development. Digoxigenin-labelled cDNA probes specific for
      the mRNA encoding ZPA, ZPB or ZPC were used to probe sections of cynomolgus
      monkey ovaries by in situ hybridization. mRNA encoding ZPA was identified in
      growing follicles at all stages and was seen in the granulosa cells of mature
      preovulatory follicles. ZPB protein and mRNA encoding ZPB were present in oocytes
      in secondary follicles and to a lesser extent in tertiary follicles, but were not
      found in primordial, primary or antral follicles or granulosa cells. ZPC protein
      and mRNA encoding ZPC were present in oocytes at all stages of folliculogenesis.
      These results suggest that each component of the ZP is produced and secreted at
      specific stages of folliculogenesis and that granulosa cells may be contributing
      to the synthesis of ZPA and ZPC.

PMID- 8984187
TI  - Immunocytochemical localization of ZP3 in primordial follicles of rabbit,
      marmoset, rhesus monkey and human ovaries using antibodies against human ZP3.
AB  - Active immunization with zona pellucida (ZP) proteins leads to depletion of
      primordial and recruited follicles in the ovary by a yet unknown mechanism. Small
      amounts of ZP present on primordial follicles or granulosa cells may be one of
      the reasons for this ovarian pathology. This study was undertaken in an attempt
      to identify the presence of ZP in or on primordial follicles and granulosa cells
      in ovaries of rabbits, common marmosets (Callithrix jacchus), rhesus monkeys
      (Macacas mulatta) and humans. Therefore, monoclonal antibodies (mAbs) and rabbit
      and mouse antisera against recombinant human ZP3 (hZP3) were produced. All these
      antibodies bound to the ZP of native intact human oocytes. Several fixatives have
      been tested on pieces of rabbit ovaries. With 4% (w/v) paraformaldehyde in PBS
      (4% PFA) followed by paraffin embedding and cryostat sections postfixed with 4%
      PFA, the most intense staining of ZP with one of the mAbs was obtained and the
      morphology was well preserved. In humans, besides the ZP, the oocyte cytoplasm
      and granulosa cells of most primordial and recruited follicles were also stained
      with these antibodies. In rhesus monkey ovaries, all primordial oocytes were also
      stained, in addition to some granulosa cells of primary follicles. In marmosets,
      small dots of immunoreactive ZP were found on 60% of the primordial follicles but
      granulosa cells were not stained. In rabbits, only minor staining of primordial
      follicles was observed. After passive immunization of rabbits with mAb 4,
      antibodies were found on both primordial and recruited follicles. These results
      clearly show the presence of ZP3 on primordial follicles and in granulosa cells,
      and this could explain the ZP-induced ovarian pathology after active immunization
      with ZP3.

PMID- 8984188
TI  - Sperm-associated protein candidates for primary zona pellucida-binding molecules:
      structure-function correlations of boar spermadhesins.
AB  - The initial binding of mammalian spermatozoa and the zona pellucida of their
      homologous oocytes appears to be mediated by a protein-carbohydrate recognition
      mechanism. Subsequent protein-protein interaction triggers the acrosome reaction
      leading to sperm penetration. Spermatozoa possess a complement of surface
      associated proteins that mediate interactions with the zona pellucida of the
      oocyte at fertilization. Both integral membrane and peripherally associated zona
      pellucida-interacting molecules have been described in a number of species. Some
      of these proteins have been shown to possess carbohydrate-binding activity and
      are therefore classified as candidates for primary gamete recognition molecules.
      The participation of any of these proteins in the in vivo situation is, however,
      a matter of debate. Here, we summarize current knowledge of the most thoroughly
      studied sperm-associated zona pellucida- and carbohydrate-binding molecules,
      paying special attention to recent evidence from our laboratories for considering
      sperm-adhesin AWN, and probably other members of its protein family, as a bona
      fide candidate for the primary gamete adhesion lectin.

PMID- 8984189
TI  - Binding of recombinant pig zona pellucida protein 1 (ZP1) to acrosome-reacted
      spermatozoa.
AB  - In an immunofluorescent study, recombinant pig zona pellucida protein 1 (pZP1)
      produced in Escherichia coli bound to acrosome-reacted spermatozoa from five
      different mammals. The location of the binding site moved from the equatorial
      region to the midpiece and tail regions during the incubation. This finding
      suggests that pig ZP1 acts as a secondary sperm-binding receptor in an
      interspecies manner and assists penetration of the spermatozoa through the zona
      pellucida. The recombinant pZP1 bound to 55 kDa protein (proacrosin) and 40 kDa
      protein of the boar spermatozoa as revealed by immunoblotting.

PMID- 8984190
TI  - Use of a specific aromatase inhibitor for determining whether there is a role for
      oestrogen in follicle/oocyte maturation, ovulation and preimplantation embryo
      development.
AB  - The specific role of oestrogen in follicular maturation, ovulation and early
      embryonic development was investigated using Fadrozole (CGS 16949A), a non
      steroidal aromatase inhibitor, to block oestrogen synthesis specifically and
      effectively in experimental animals. Induced and normal cyclical follicular
      maturation as well as normal and hCG/LH-induced ovulation were relatively
      unaffected by significantly depleting oestrogen in all animals (hamsters,
      rabbits, monkeys) studied other than rats. Fadrozole treatment significantly
      reduced the number of healthy antral follicles produced and the ovulatory
      response to exogenous hCG of immature rats primed with pregnant mares' serum
      gonadotrophin. The effect was specific, in that exogenously administered
      oestrogen reversed the blockade. Depletion of oestrogen, starting early in pro
      oestrus in hamsters, had no effect on ovulation, oocyte maturation and
      fertilization, as normal implantation sites were seen on day 6 after coitus. In
      rabbits, oestrogen depletion during the periovulatory phase affected oviductal
      morphology and function. Although fertilization was not impaired, early embryo
      development did not appear to be normal. In monkeys, oestrogen depletion during
      the follicular phase did not lead to a block of follicular maturation or
      ovulation but resulted in a significant reduction in secretion of cervical mucus.
      Administration of either Fadrozole or Tamoxifen during the early luteal phase in
      cyclic monkeys that were allowed to mate prevented implantation and this appears
      to be due to impaired fertilization or faulty embryo development. These results
      suggest that, although there is a clear requirement for oestrogen to support the
      reproductive cycle in the female, the need for oestrogen in regulating specific
      events is species dependent.

PMID- 8984192
TI  - Comparative structural and antigenic properties of zona pellucida glycoproteins.
AB  - For rational and optimal use of the zona pellucida glycoproteins as antigens for
      immunocontraception, a comprehensive understanding of their structure, function
      and antigenic properties is necessary. The antigenic relatedness of the pig zona
      pellucida glycoproteins were analysed and compared with three glycoproteins
      cloned from ovarian cDNA libraries of the anuran Xenopus laevis. The vitelline
      envelope from Xenopus laevis eggs (an extracellular matrix structure equivalent
      to the mammalian zona pellucida) is composed of glycoproteins that are homologous
      to the three mammalian zona pellucida glycoproteins, ZPA, ZPB and ZPC. The
      experimental results were used to make antigenic and functional (fertilization)
      predictions about zona pellucida glycoproteins. These studies provide a
      potentially useful perspective for devising immunocontraceptive methods of
      fertility regulation.

PMID- 8984193
TI  - Regulation of follicular maturation by human ovarian follicular fluid peptide.
AB  - Follicular development, ovulation and luteal function are controlled by
      gonadotrophins. However, recent evidence indicates that local factors are also
      responsible for the regulation of folliculogenesis. In addition to their
      endocrine action on pituitary gonadotrophins, inhibin, activin and follistatin
      also have a paracrine role in follicular maturation. An ovarian follicular fluid
      peptide (OFFP) has been identified from sheep and humans. Purification of OFFP
      has been achieved by ultrafiltration and gel chromatography with further
      purification by fast performance liquid chromatography and reversed phase-high
      pressure liquid chromatography. OFFP is a small (< 5 kDa) peptide that competes
      with FSH in binding to granulosa cells in vitro and inhibits progesterone
      secretion from granulosa cells in culture. Immunohistochemical localization
      revealed the presence of OFFP mainly in granulosa cells of ovarian follicles.
      Furthermore, the peptide caused apoptosis in granulosa cells and induced
      follicular atresia. OFFP may act indirectly on oocytes via its effect on
      granulosa cells. The peptide from ovarian follicular fluid appears to have an
      important autocrine or paracrine role in the regulation of folliculogenesis.

PMID- 8984191
TI  - Follicular development through preantral stages: signalling via growth factors.
AB  - Although gonadotrophins, particularly FSH, are the primary pituitary regulators
      of ovarian folliculogenesis, the involvement of ovarian-derived growth factors in
      follicular growth and maturation has become increasingly apparent over the past
      decade. Regulators of ovarian somatic cells can be broadly divided into (1)
      mitogenic factors, and (2) differentiation-induction factors, based on two
      primary cellular requirements, that is, proliferation and differentiation that
      are fundamental to folliculogenesis and ovarian functions. In this article,
      direct as well as indirect evidence is presented that highlights the roles of
      epidermal growth factor--a mitogen, and transforming growth factor beta--a
      differentiation-induction factor, in modulating gonadotrophin action in the
      ovary, particularly in the preantral follicles. An exquisitely timed and
      regionalized expression of these two types of peptide factor, along with their
      membrane receptors, may determine the differential success of follicle
      development, hence, allowing selection of the best oocytes for fertilization and
      subsequent development.

PMID- 8984197
TI  - Ionic fluxes through myelin membrane vesicles.
AB  - Technical difficulties and a lack of reproducibility in procedures aimed at the
      production of myelin vesicles have delayed functional studies on membrane
      transport through myelin. Myelin vesicles could provide an excellent model for
      the study of the transport of ions and water, etc., across this type of membrane.
      They could also help improve our understanding of the molecular functions of the
      myelin sheath. In this investigation, a novel, nonaggressive method of producing
      central nervous system myelin vesicles is presented. Purified bovine myelin was
      incubated with iminodiacetic acid (an insoluble chelating agent that is easy to
      remove and does not interfere with further functional assays), and rendered
      insoluble on 1% crosslinked polystyrene beads (Chelex-100). Myelin vesicles
      obtained were impermeable to sugars (sucrose, glucose, and galactose), but showed
      a degree of permeability towards potassium salts as determined by light
      scattering. Further experiments with fluorescent probes revealed an electrogenic
      K+ influx, as measured by oxonol V fluorescence quenching, and a significant H+
      permeability measured using the pH-sensitive probe acridine orange. H+
      permeability was not detected in control liposomes made from the same endogenous
      myelin lipids without protein. The results are discussed with reference to
      previous studies performed using purified myelin proteins in reconstituted
      systems. The relevance of these results with respect to ionic transport across
      myelin membrane is discussed.

PMID- 8984195
TI  - Examination of TAR-independent Trans activation by human immunodeficiency virus
      type 1 Tat in human glial cells.
AB  - Astrocytic glial cells derived from central nervous system (CNS) can support
      human immunodeficiency virus type 1 (HIV-1) replication in cell culture, may be
      infected in tissue culture, and are thought to be a large HIV-1 reservoir in
      vivo. The Tat protein of HIV-1 interacts with a cis-acting target sequence
      referred to as TAR. However, Tat can also stimulate gene expression directed from
      some heterologous promoters and, in certain circumstances, an HIV-1 long terminal
      repeat (LTR) that lacks the TAR element. Therefore, we attempted to investigate
      Tat trans activation of HIV-1 LTR in the astrocytic glial cells. Using
      transfection of LTR-reporter gene constructs and HIV-1 proviral constructs, we
      demonstrate TAR-dependent replication in astrocytic cells. We also examined the
      expression of HIV-1 env gene from an LTR that lacks TAR element. In a previous
      study (Kim and Panganiban: J Virol 67:3739-3747, 1993), we observed that env
      expression is trans activated only by the full-length Tat protein through a TAR
      independent manner in HeLa cells. However, in astrocytic glial cells, the trans
      activation of env expression from the LTR-lacking TAR element was mediated by the
      first exon peptide of Tat as well as the full-length Tat peptide through a post
      transcriptional mechanism rather than a transcriptional one. This result suggests
      that cell type-specific factor(s) is involved in the TAR-independent Tat
      responsiveness.

PMID- 8984198
TI  - Glial growth factors I-III are specific mitogens for glial cells.
AB  - Recently we identified three novel Schwann cell mitogens named GGF (glial growth
      factor)-I (34 kDa), GGF-II (59 kDa), and GGF-III (45 kDa), and provided evidence
      that they are three distinct but structurally related members of a larger family
      of factors, which includes heregulin, neu differentiation factor, and
      acetylcholine receptor-inducing activity (ARIA). We report here the
      characterization of the mitogenic and trophic activities for all three forms of
      GGF on rat Schwann cells and several other cell types. GGF-I, GGF-II, and GGF-III
      are potent mitogens for rat Schwann cells in vitro at nanomolar concentrations,
      whereas at lower concentrations they promote Schwann cell survival, in the
      absence of cAMP elevating agents. Forskolin, an adenylate cyclase activator,
      potently synergizes with the GGFs by an indirect mechanism, possibly involving
      transcriptional activation of GGF receptor(s). In addition, the GGFs stimulate
      DNA synthesis in rat glioma C6 cells, and in SK-BR-3 cells, which overexpress the
      p185 neu/erbB2. Fibroblasts obtained from different sources are weakly stimulated
      by GGFs, whereas PC12 cells are unable to respond under a variety of experimental
      conditions. These observations are consistent with the proposal that GGF-I, GGF
      II, and GGF-III are a set of potent glial cell mitogens and putative ligands of
      members of the EGF receptor family, namely p185 neu/erbB2, p160/erbB3, and
      p180/erbB4, which may play important roles in the development, regeneration, and
      tumor biology of the peripheral nervous system.

PMID- 8984196
TI  - Characterization of rat NCA/CD9 cell surface antigen and its expression by normal
      and malignant neural cells.
AB  - As part of investigations on ethylnitrosourea (EtNU)-induced neuro-oncogenesis in
      the rat, we have produced monoclonal antibodies (Mabs) specific for neural cell
      surface antigens (NCAs) by immunization with cells of the clonal tumorigenic
      neural rat cell line BT4Ca. Mabs designated as anti-NCA (alpha NCA1, alpha NCA2,
      alpha NCA3, alpha NCA4, and alpha NCA5) recognize proteins of 25 kDa and 23 kDa,
      as shown by immunoprecipitation and Western blot. The predominant 25-kDa protein
      was purified from BT4Ca cells by immunoaffinity chromatography with immobilized
      Mab alpha NCA1 and identified by N-terminal sequencing as the rat homologue of
      the CD9 antigen. Identification of proline as N-terminal amino acid of the
      purified protein suggests post-translational modification of CD9 in the rat
      central nervous system. The NCA/CD9 protein was localized in distinct regions of
      fetal and adult rat brain by immunofluorescence staining of frozen sections. Flow
      cytometric analyses of isolated fetal rat brain cells (FBC) showed that the
      proportion and number of NCA/CD9-expressing cells increased during prenatal
      development. Immunoreactivity of approximately 40% of brain cells isolated 13
      days post conception (p.c.) indicated that NCA/CD9 is expressed by neuronal
      precursors at this stage of development. In primary cultures of rat FBC isolated
      18 days p.c., the NCA/CD9 antigen was expressed by all premature and mature
      astrocytes, oligodendrocytes, ependymal cells, and microglial cells, but not by E
      N-CAM-expressing neuronal progenitor cells and neurons. Furthermore, eight out of
      ten EtNU-induced malignant neural rat cell lines as well as EtNU-induced tumors
      of the central and peripheral nervous system exhibited intermediate or strong
      immunoreactivity with Mab alpha NCA1. Expression of the NCA/CD9 protein is,
      therefore, characteristic of both normal glial precursor cells and their
      malignant counterparts in the rat.

PMID- 8984199
TI  - Expression of polypeptide variants of receptor-type protein tyrosine phosphatase
      beta: the secreted form, phosphacan, increases dramatically during embryonic
      development and modulates glial cell behavior in vitro.
AB  - Glial cells express three splicing variants of a receptor-type protein tyrosine
      phosphatase called RPTP beta. Two are receptor forms that differ in a large
      extracellular domain. The third is a secreted proteoglycan called phosphacan that
      lacks the cytoplasmic phosphatase domains. We have now identified, by
      immunoblotting, proteins corresponding to these three forms of RPTP beta in rat
      C6 glioma cells and brain. The short receptor form is much more prevalent than
      the full-length receptor in C6 glioma cells. Phosphacan is much more abundant
      than either of the receptor forms in rat brain, and its expression increases
      progressively during embryonic development, while the receptor forms show only
      moderate changes. In contrast to the long form and phosphacan that were detected
      as proteoglycans, the short receptor form, lacking the large alternatively
      spliced domain, was not detected as a chondroitin sulfate proteoglycan. We
      recently showed that phosphacan binds to the neuron-glia cell adhesion molecule,
      Ng-CAM, and we now report that glia expressing RPTP beta adhere and extend
      processes on substrates coated with Ng-CAM. After one day in culture, however,
      the glia retract their processes and often lift off the substrate. Conditioned
      medium from glial cells, which contains large amounts of phosphacan, inhibits
      glial adhesion to Ng-CAM, and depletion of phosphacan from the conditioned medium
      by immunoadsorption reduces the inhibitory activity. The results show that
      phosphacan increases dramatically during development, and indicate that secreted
      forms of RPTP beta can modulate glial cell adhesion and behavior.

PMID- 8984201
TI  - A new organotypic culture method to study the actions of steroid hormones on the
      nervous system.
AB  - A new organotypic culture method for growing slices of nervous system tissue,
      based on the use of hyaluronic acid as a growth supporting milieu, is described.
      This method allows cultures derived from either fetuses or newborns to grow and
      develop with markedly reduced amounts of added serum. Organotypic cultures from
      fetal rat hypothalamus were exposed to 17 beta estradiol and compared to control
      cultures exposed to the ethanol vehicle. When exposed to estradiol, cultures
      showed an outgrowth of thick nerve fibers that was accompanied by an elevation in
      the number of microtubules present in the neuronal processes, an increment in the
      number of synapses, and an increased morphological differentiation of synaptic
      terminals. Freeze-fracture analysis of neuronal membranes from estradiol-treated
      cultures revealed a significant increase in the number of exoendocytotic images
      and a decrease in the number of intramembranous particles. Estradiol's effects
      parallel those found in in vivo studies, indicating that hyaluronic acid-based
      organotypic cultures represent an appropriate model to study hormonal influences
      on the developing nervous system.

PMID- 8984200
TI  - Addition of tetrodotoxin alters the morphology of thalamocortical axons in
      organotypic cocultures.
AB  - Living organotypic cocultures of rat thalamic and cortical explants were used to
      examine the effects of blocking action potential activity on the morphological
      development of axons in the mammalian neocortex. Studies in vivo have suggested
      that blocking sodium channel-dependent activity influences the growth
      characteristics of thalamocortical axons during development. We have extended
      these observations by using an in vitro system that affords more direct
      observational analysis of the early events of axonal growth in an accessible
      cellular environment DiI-labeled thalamocortical axons grow exuberantly into the
      target cortex and establish axonal connections that reflect the events of early
      thalamocortical afferent development. Within these cocultures, the morphological
      features of DiI-labeled axons can be readily distinguished. Tracings of
      thalamocortical axons were quantitated with respect to number, length, and
      termination pattern of axonal branches, as well as number of varicosities.
      Addition of the voltage-dependent sodium channel blocker, tetrodotoxin, to
      cocultures did not change the general pattern of thalamocortical axonal ingrowth
      or the average length of collateral branches of these axons. However, in the
      presence of tetrodotoxin, axons were more highly branched, with an increased
      number of varicosities as compared to untreated cocultures. This pattern of
      axonal growth and branching may reflect the activity-dependent fine-tuning and
      trimming of collaterals that occur as thalamic afferents begin to refine their
      cortical territory. Our observations in thalamocortical cocultures are consistent
      with the view that neuronal activity modulates the pattern of axonal growth and
      development.

PMID- 8984202
TI  - Antisense oligodeoxynucleotides to bax mRNA promote survival of rat sympathetic
      neurons in culture.
AB  - Previous in vitro studies have shown that the presence of high levels of Bax
      protein accelerated the rate of cell death following growth factor deprivation
      and that the ratio of cell death repressor Bcl-2 to cell death effector Bax may
      determine the susceptibility to apoptosis. Both Bcl-2 and Bax protein expression
      has been detected in sympathetic neurons in vivo, and overexpression of bcl-2 in
      cultured sympathetic neurons prevented apoptosis after deprivation of nerve
      growth factor (NGF). In the present study, we investigated the expression of bax
      and bcl-2 in primary cultures of sympathetic neurons from rat superior cervical
      ganglia. Furthermore, we tested the effects of a partially phosphorothioated bax
      antisense oligodeoxynucleotide (ODN) on the survival of sympathetic neurons in
      cultures supplied with suboptimal concentrations of NGF (0.5 ng/ml). A
      constitutive expression of bax mRNA at high levels was detected by reverse
      transcription and polymerase chain reaction which did not change significantly
      following NGF reduction or treatment with bax antisense ODN. A decrease in Bcl-2
      immunoreactivity was observed by immunocytochemistry in tyrosine hydroxylase
      positive neurons when cultured under suboptimal NGF concentrations, whereas Bcl-2
      immunolabeled non-neuronal cells were not affected. Maximal number of neurons was
      obtained in control cultures containing 50 ng/ml of NGF. Few neurons survived in
      cultures grown in 0.5 ng/ml of NGF for 2 days (12.0 +/- 1.5% of controls, mean +/
      SEM). Addition of two control ODNs at 1 microM had no effect on neuronal
      survival (10.1 +/- 1.2% and 11.0 +/- 1.3%, respectively), while the number of
      neurons was significantly increased in NGF-reduced cultures treated with a bax
      antisense ODNs (1 microM) (31.5 +/- 1.9%). Administration of fluorescein-labeled
      ODNs demonstrated intracellular uptake into cultured neurons. Treatment with bax
      antisense ODNs caused a significant reduction of Bax protein levels in SCG
      neurons by 46 +/- 2.6% as assessed by immuno-cytochemistry and digital image
      analysis. Taken together, our data demonstrate a constitutive expression of bax
      mRNA in sympathetic neurons suggesting that activation of bax expression may not
      be required for neuronal cell death after NGF withdrawal. After changing to
      suboptimal NGF concentrations, the cell-specific reduction in Bcl-2
      immunoreactivity preceded morphological signs of degeneration indicating that
      growth factor starvation may down-regulate neuronal bcl-2 expression. Treatment
      with bax antisense ODNs indicated that suppression of Bax protein synthesis may
      promote neuronal survival in the threshold situation of insufficient trophic
      support.

PMID- 8984206
TI  - Probable association between urinary tract infections (UTI) and common diseases
      of infancy and childhood: a hospital-based study of UTI in Durban, South Africa.
AB  - In a retrospective study of UTI among 54 pediatric patients in a tertiary
      hospital, a striking finding was that UTI seldom existed as a single condition.
      In 86 per cent of cases, UTI was part of other common diseases: gastroenteritis
      (in 35 per cent of UTI patients), protein energy malnutrition (in 43 per cent)
      and acute respiratory infection (24 per cent). Presenting symptoms were similar
      in children with or without UTI. Other features included infrequency of urinary
      tract signs (13 per cent), resistance of infecting organisms to first line
      antibiotics and urinary tract structural abnormalities in only two patients of 36
      investigated by ultrasonograms; both the latter patients had easily diagnosable
      underlying diseases (TB spine, posterior urethral valves). These findings require
      confirmation by prospective studies as they may have implications for management
      of UTI in hospitals in developing countries.

PMID- 8984205
TI  - Neonatal tetanus in rural and displaced communities in the East Nile Province.
AB  - A retrospective neonatal tetanus survey was conducted among rural and displaced
      communities in the East Nile Province in the Sudan. The results showed that
      neonatal tetanus was a major cause of neonatal mortality. The incidence in the
      displaced community was more than double that in the stable rural community, 7.1
      and 3.2 per 1000 live births, respectively. Coverage with two doses of tetanus
      toxoid was about 58 per cent in both areas, with a drop-off rate of 15 per cent.
      Making use of missed opportunities to vaccinate regular attendants of antenatal
      care services would have increased coverage in both areas. Wrong beliefs and
      attitudes towards tetanus toxoid were detected among schoolgirls and teachers in
      the two areas.

PMID- 8984194
TI  - Heterologous retinal cultured neurons and cell adhesion molecules induce
      clustering of acetylcholine receptors and polynucleation in mouse muscle BC3H-1
      clonal cell line.
AB  - Several features of the clonal cell line BC3H-1 resemble those of embryonic
      muscle cells at their early stage of development (Patrick et al.: J Biol Chem
      252:2143-2153, 1977). Under normal culture conditions, fully differentiated BC3H
      1 cells possess a spindle-shaped, muscle-like morphology with a single nucleus.
      Like embryonic muscle cell counterparts, they neither express the epsilon subunit
      nor exhibit the clustered organization of the nicotinic acetylcholine receptor
      (AChR) characteristic of mature myocytes. Instead, AChRs are evenly distributed
      upon the sarcolemma upon differentiation. Here we report that BC3H-1 cells can be
      induced to express AChR clusters by co-culturing the cell line with heterologous
      retinal neurons, which establish contacts with former cells. Clustering was also
      triggered by pretreating the culture substratum with several cell adhesion
      molecules. Polynucleation, a phenomenon observed in mature myotubes in vivo, was
      also observed in BC3H-1 cells under the two sets of experimental conditions. AChR
      clustering and polynucleation, both characteristic of the mature postsynaptic
      region, can thus be induced in BC3H-1 cells by at least two quite distinct
      pathways: neuronal cell contact and/or cell adhesion molecules. It is suggested
      that heterologous retinal neurons can elicit only an incomplete differentiation
      of BC3H-1 cells, failing to concentrate the clusters beneath the neuronal
      endings, and failing to induce expression of the epsilon subunit, characteristic
      of the mature AChR.

PMID- 8984207
TI  - Reduction in in-hospital mortality of children with malnutrition.

PMID- 8984208
TI  - Aetiology of childhood diarrhoea in an Egyptian rural community.

PMID- 8984210
TI  - Fetal and neonatal deaths in a South Indian hospital.

PMID- 8984209
TI  - Lack of evidence of HIV-2 infection among multitransfused thalassemic children in
      the city of New Delhi.

PMID- 8984212
TI  - Salivary secretory IgA reference values in Brazilian healthy children.

PMID- 8984211
TI  - Haemorrhagic colitis due to Escherichia coli O157:H7 in Kenya.

PMID- 8984213
TI  - A study of iron requirement during weaning by total body iron determined by
      haemoglobin, serum ferritin, and body weight.

PMID- 8984215
TI  - Malaria during pregnancy.

PMID- 8984204
TI  - Child growth during weaning depends on whether mother is pregnant again.
AB  - Few longitudinal studies are available which relate data on breastfeeding and
      growth of the last-born child to data on the mother's subsequent pregnancy. The
      purpose of the present prospective study from Bhutan was to compare growth rate
      of children weaned during a subsequent pregnancy, with those of children weaned
      at the same age, but from non-pregnant mothers. Measurements of weight of 113
      children and interviews with their mothers were done monthly through 32 months
      during the children's first 3 years of life. The period of overlap between
      lactation and pregnancy had a median duration of 5 months, and increased with an
      average of one week for each month reduction in the subsequent birth interval (P<
      0.01). Children who stopped breastfeeding during their mothers' subsequent
      pregnancy showed a reduced growth rate during the last months before termination
      of breastfeeding when compared to children weaned at the same age, but from non
      pregnant mothers (P = 0.04), and when compared to children who continued
      breastfeeding (P = 0.06).

PMID- 8984218
TI  - Iron status of newborns born to iron deficient anaemic mothers.
AB  - Haemoglobin, serum iron, total iron binding capacity, and serum ferritin were
      determined in newborns of 16 mothers with iron deficiency anaemia, 28 mothers
      with non-anaemic iron deficiency, and nine mothers with normal haemoglobin and
      serum ferritin levels. The results showed that there were no significant
      differences in the mean values of haemoglobin, serum iron, and total iron binding
      capacity among the newborns in the three groups. However, the mean value of serum
      ferritin differed significantly among the three groups, with the lowest values
      found in newborns of mothers with iron deficiency anaemia.

PMID- 8984216
TI  - Associated infections in persistent diarrhoea--another perspective.
AB  - Seventy-eight children diagnosed as cases of persistent diarrhoea (PD) from 1
      month to 5 years of age (mean age 8.92 months) hospitalized during a 2-year study
      period were screened for the presence of non-gastrointestinal infections.
      Clinical screening suggested acute respiratory infection (ARI) in 30 per cent
      cases, urinary tract infection (UTI) in 19 per cent and acute suppurative otitis
      media (ASOM) in 10 per cent of cases. Investigations revealed pneumonia on chest
      X-ray (39 per cent), positive urine culture (32 per cent), leucocytosis (31 per
      cent) and positive blood culture (22 per cent). Seven cases (9 per cent) of
      pneumonia and 10 cases (13 per cent) diagnosed to have UTI were not identified on
      clinical screening and could be detected only after investigations. E. coli was
      the commonest organism isolated from urine culture (23 per cent) and blood
      culture (14 per cent); 54 per cent of cases had one or the other associated
      infection and 28 per cent were suffering from more than one infection. Bacterial
      pathogens were more frequently isolated from blood in children < 6 months (P <
      0.01), with vomiting (P < 0.001), and severe malnutrition (P < 0.05); from urine
      in association with fever (P < 0.001), duration of diarrhoea > 4 weeks (P <
      0.05), and vomiting (P < 0.001). Pneumonia was detected on chest radiograph more
      frequently in children with severe malnutrition (P < 0.001). Sixty eight per cent
      of cases were successfully treated with dietary management and appropriate
      treatment of associated infections and 18 per cent of cases died. Mortality was
      highest in association with sever oral thrush, severe malnutrition, septicaemia,
      and ARI. Our results suggest that majority of cases of PD are associated with one
      or the other non-gastrointestinal infections particularly UTI and ARI which may
      be missed on clinical examination unless efforts are made to investigate these
      children. Early detection and appropriate management of these infections can
      considerably modify hospital course and outcome.

PMID- 8984214
TI  - Nutritional status of infants and young children in the Arabian Gulf countries.

PMID- 8984217
TI  - Acute Chagas' disease: plasma levels of alpha-2-macroglobulin and C-reactive
      protein in children under 13 years in a high endemic area of Bolivia.
AB  - We measured the levels of two human acute phase proteins (APP), alpha-2
      macroglobulin (A2M) and C-reactive protein (CRP), in sera of 56 healthy and 84
      acute chagasic children aged from 1 to 13 years old, from a highly endemic area
      in Bolivia. In such areas, children are continuously exposed to vectors and the
      frequency of acute cases increases with age. Quantitation of A2M and CRP were
      performed using sandwich ELISAs, that were shown to be sensitive, reproducible
      and suited for studying many samples rapidly. A2M levels observed were higher in
      healthy younger children, decreasing with age until children reached their teens,
      and their distribution suggested a relationship between A2M concentration and age
      that could be consistently expressed by a power function. The same does not occur
      with CRP levels. Concentrations of A2M were age-adjusted to allow comparison
      using sera collected from children with different ages. Both A2M and CRP were
      significantly increased in acute chagasic children. Since parasites are commonly
      present in blood and tissues during the acute phase of Chagas' disease, it is
      possible that the high levels of A2M may act as inhibitors of a high load of
      proteinases, derived either from the parasites, from host cell damage or from
      both.

PMID- 8984203
TI  - B61, a ligand for the Eck receptor protein-tyrosine kinase, exhibits neurotrophic
      activity in cultures of rat spinal cord neurons.
AB  - Although the Eph subfamily represents the largest group of receptor protein
      tyrosine kinases, the biological roles of the Eph-related receptors and their
      ligands are not well understood. B61 has been identified recently by receptor
      affinity chromatography as a ligand for the Eph-related receptor Eck (Bartley et
      al.: Nature 368:558-560, 1994). Here we show that Eck immunoreactivity is
      localized in areas of the embryonic rat spinal cord that are rich in axons,
      suggesting that Eck plays a role in this region of the developing nervous system.
      To examine the biological function of Eck, monolayer cultures of dissociated
      cells from embryonic rat spinal cord were treated with soluble B61. With an ED50
      of approximately 10 ng/ml, B61 treatment improved the survival of the overall
      neuronal population. Furthermore, in the presence of B61 neurites were longer and
      more elaborated. B61 similarly affected survival and neurite length in cultures
      enriched in motor neurons. These neurotrophic effects of B61 were not observed in
      the presence of anti-Eck antibodies, indicating that these effects are likely to
      be mediated by the Eck receptor.

PMID- 8984222
TI  - Long-term anticonvulsant therapy in tuberculous meningitis--a four-year follow
      up.
AB  - A treatment protocol for long-term anticonvulsant therapy (ACT) in children with
      tuberculous meningitis (TBM) has been followed depending upon clinical
      characteristics and EEG/CT scan findings suggestive of the underlying cause of
      convulsions. Sixty-three children which included all patients with focal seizures
      (FS), and those with generalized tonic and clonic seizures (GTCS), and tonic
      spasms (TS) manifesting more than once during hospitalization and/or associated
      with abnormal CT/EEG findings were given long-term ACT (Group A). Thirty-eight
      cases with GTCS before hospitalization, and/or not more than one seizure during
      first week of hospitalization and without any specific CT/EEG abnormalities
      (Group B) and 35 cases without any seizures (Group C) did not receive any ACT.
      Forty-four patients who were finally discharged on long-term ACT, were given
      phenobarbitone (57 per cent), phenytoin (23 per cent), and a combination of
      phenobarbitone+phenytoin (14 per cent), and phenobarbitone+sodium valproate (7
      per cent). Follow-up was continued for 4 years with 93, 84 and 81 per cent
      attendance, respectively, in groups A, B and C. Some of the side-effects observed
      with anti-convulsant drugs included gingival hypertrophy in 11 out of 16 cases
      (69 per cent) on phenytoin, hyperkinetic behaviour in 3 out of 34 (9 per cent)
      cases on phenobarbitone, hypocalcaemia in 3 out of 44 cases (7 per cent),
      hypophosphataemia in 10 out of 44 cases (23 per cent) and increase in alkaline
      phosphatase in 14 out of 44 cases (32 per cent). CT scan of brain repeated in six
      cases with multiple tuberculomas showed marked improvement. While 4 out of 41 (10
      per cent) cases in group A had recurrence of seizures in the follow-up, only 2
      out of 28 cases (7 per cent) in group B presented with GTCS during first 3 months
      after discharge which was successfully controlled by long-term ACT in later part
      of the follow-up. Two out of 21 cases (10 per cent) in group C also presented
      with myoclonic seizures 3 and 5 months after discharge. There was no
      statistically significant difference in the recurrence/appearance of seizures in
      the three groups (P = > 0.05). Our results suggest that long-term ACT is not
      indicated in all cases of TBM with seizures. In view of the known side-effects of
      anticonvulsant drugs and danger of interaction with antitubercular drugs, it is
      mandatory to clinically evaluate the patients, identify the cause and restrict
      long-term ACT only to those cases who are likely to have some abnormal focus
      resulting in secondary epilepsy. All the cases with FS and some of the patients
      with GTCS and TS may need to be started on ACT. However, a close follow-up is
      necessary in all particularly in those for whom ACT has been withheld.

PMID- 8984223
TI  - Communications to the 3rd World Congress of Science and Football. Cardiff, Wales,
      9-13 April 1995. Abstracts.

PMID- 8984221
TI  - Convulsions in tuberculous meningitis.
AB  - One-hundred-and-thirty-six children below 12 years of age hospitalized with a
      diagnosis of tuberculous meningitis (TBM) have been investigated to identify the
      underlying cause of convulsions. One-hundred-and-one children (74 per cent)
      presented with seizures before and/or during hospitalization. Generalized tonic
      and clonic seizures (GTCS) were the commonest (58 per cent) type of seizures
      followed by focal seizures (FS) (38 per cent) and tonic spasms (TS) (4 per cent).
      EEG changes were more frequently observed in cases with FS and in those children
      with GTCS who presented after first week of hospitalization. EEG findings
      included generalized dysrythmia with paroxysmal slow activity (38 per cent),
      interhemispheric asymmetry (23 per cent), multiple spike and wave pattern (10 per
      cent), and focal spike and wave pattern (15 per cent). CT scan findings were more
      common in those children with GTCS and TS who presented with recurrent seizures
      and/or seizures manifesting after first week of hospitalization. FS presenting at
      any stage of the disease were associated with CT scan abnormalities.
      Abnormalities detected in CT scan of brain included meningeal enhancement (55 per
      cent), hydrocephalus (32 per cent), tuberculomas (27 per cent), and cerebral
      infarctions (13 per cent). Clinical presentation and investigations indicate that
      the probable cause of convulsions could be attributed to cerebral edema (57 per
      cent), syndrome of inappropriate secretion of antidiuretic hormone (35 per cent),
      hydrocephalus (32 per cent), tuberculoma (27 per cent), abnormal electric focus
      (25 per cent), and cerebral infarction (13 per cent).

PMID- 8984220
TI  - Aspergillus fumigatus specific antibodies in multitransfused children with human
      immunodeficiency virus (HIV) infection in relation to serum levels of Interleukin
      2, gamma Interferon and tumour necrosis factor.
AB  - Anti-Aspergillus fumigatus antibodies (IgG and IgE class) and serum levels of
      cytokines (gamma Interferon, Interleukin-2 and tumour necrosis factor-alpha) were
      studied in multitransfused (MT) children in relation to human immunodeficiency
      virus (HIV) infection. The specific antibodies to Aspergillus fumigatus were
      present in 25 per cent of MT children seropositive for HIV as compared to only 2
      per cent among HIV-negative MT children (X2 = 14, P < 0.001). Estimation of serum
      cytokines level in MT children showed that the asymptomatic HIV-infected children
      had elevated levels of gamma interferon (Y-IFN) and tumor necrosis factor-alpha
      (TNF-alpha) without any alteration of Interleukin-2 (IL-2) level, compared to HIV
      negative group. However, clinically diagnosed cases of AIDS in the HIV-infected
      group showed elevation of all the three cytokines levels as compared to HIV
      negative group, as well as asymptomatic HIV infected group. Presence or absence
      of concomitant A. fumigatus infection did not lead to alteration of Y-IFN and IL
      2 level in the HIV infected group, while TNF-alpha levels were markedly raised in
      the cases with evidences of presence of A. fumigatus specific antibodies
      irrespective of whether the group belonged to asymptomatic HIV infection or
      clinically proven cases of AIDS. The significance of these altered cytokines
      profile with respect to occurence of A. fumigatus infection in HIV-positive MT
      children has been discussed.

PMID- 8984226
TI  - The effect of preservation temperature and period on resuscitation of the
      ischemically damaged canine pancreas during preservation by the two-layer
      (University of Wisconsin solution/perfluorochemical) method.
AB  - We have shown that 24 to 48 hour-preservation by the two-layer (University of
      Wisconsin solution (UW)/perfluorochemical (PFC)) method at 4 degrees C
      resuscitates a canine pancreas subjected to 90 min of warm ischemia. However, it
      is necessary to shorten preservation period for resuscitation of the ischemically
      damaged pancreas in a clinical simultaneous pancreas-kidney transplantation. The
      purpose of this study was to clarify the effect of preservation temperature and
      period on the resuscitation of the ischemically damaged pancreas during
      preservation by the two-layer method. First of all, we examined the possibility
      of resuscitation of the ischemically damaged pancreas during short-term
      preservation by the two-layer method. After 90 minutes of warm ischemia, canine
      pancreases were preserved by the two-layer method at 4, 20, or 37 degrees C. In
      control group, the pancreas graft was autotransplanted without preservation.
      Graft viability was judged by graft survival after autotransplantation. Pancreas
      grafts subjected to 90 min of warm ischemia were not viable (0/5). At 4 degrees
      C, 5 to 12 hr-preservation did not resuscitate the grafts (0/3 and 0/3
      respectively). At 20 degrees C, 3 and 5 hr-preservation resuscitated the grafts
      (3/5 and 5/5 respectively), although 1 and 8 hr-preservation were not successful
      (0/3 and 0/3 respectively). At 37 degrees C, all the grafts were not resuscitated
      irrespective of preservation period. It was clear that the ischemically damaged
      pancreas was resuscitated during shot-term preservation by the two-layer method
      only at 20 degrees C. Secondly, we measured tissue adenine nucleotide levels by
      high performance liquid chromatography and pancreatic tissue perfusions using H2
      clearance technique on reperfusion and examined the viability of vascular
      endothelium by nuclear trypan blue staining to make clear the necessary
      conditions for resuscitation of the ischemically damaged pancreas at 20 degrees
      C. ATP tissue levels in one hr-preserved grafts were 2.55 +/- 0.38 mumol/g dry
      weight and were significantly lower compared with the levels in 5 and 8 hr
      preserved grafts, 9.40 +/- 2.09 (P < 0.01) and 7.37 +/- 1.06 mumol/g dry weight
      (P < 0.01) respectively. On the other hand, nuclear trypan blue uptakes of
      endothelial cells in 8 hr-preserved grafts were 37.6 +/- 11.6% and were
      significantly higher than 1 hr- and 5 hr-preserved grafts 5.6 +/- 4.5 (P < 0.01)
      and 5.0 +/- 3.0% (P < 0.01) respectively. As a consequence, pancreatic tissue
      perfusions in 8 hr-preserved grafts, 31.0 +/- 3.5 ml/min/g, were significantly
      lower than 1 hr- and 5 hr-preserved graft 72.0 +/- 11.6 (P < 0.01), 63.9 +/- 13.3
      ml/min/g (P < 0.01) respectively. However, thromboxane A2 synthesis inhibitor
      (OKY046 0.1 mM/L) decreased the percentage of trypan blue uptake (8.2 +/- 3.6%)
      without interfering ATP synthesis (8.44 +/- 0.92 mumol/g dry weight) in 8 hr
      preserved pancreas and tissue perfusions after reperfusion were dramatically
      improved (99.6 +/- 11.8 ml/min/g). As a result the ischemically damaged pancreas
      was resuscitated (4/5, 80%). It was suggested that 1 hr-preservation was not
      enough to synthesize ATP, which was essential to repair damaged cells, although
      vascular endothelial cells were maintained. Eight hr-preservation incurs
      endothelial cell damage although ATP tissue levels were maintained and
      consequently microcirculation was disturbed at reperfusion but OKY046 protects
      endothelial cells against preservation/reperfusion injury. As a consequence, the
      ischemically damaged pancreas was resuscitated. We conclude that short-term (3 to
      8 hr) preservation at 20 degrees C by the two-layer method with OKY046
      accelerates ATP synthesis, which is essential for repairing damaged cells and
      protects microvascular endothelial cells. This makes it possible to resuscitate
      the canine pancreas graft subjected to 90 min warm ischemia. This method holds
      promise for pancreas-kidney transplantation from cardiac arrest donors.

PMID- 8984224
TI  - [Identical twin sisters with IgA nephropathy].
AB  - This report described 45-year-old identical twin sisters with IgA nephropathy.
      Case 1 presented with microscopic hematuria and proteinuria at the age of 39.
      Case 2 was found proteinuria at the age of 32. Both the physical examination and
      laboratory data of these cases were normal. Serum level of IgA was not elevated.
      The renal biopsy specimen of two cases showed slight mesangial proliferation by
      light microscopy and mesangial IgA deposition by immunofluorescence microscopy.
      Their serotype for HLA was found to be HLA-A2, A24, Bw35, Cw1, Cw3, DRw8, DRw12.
      Several reports indicated the familial occurrence of patients with IgA
      nephropathy and a strong association with HLA-Bw35 in those patients. The present
      cases also suggested that an abnormal immune response-linked HLA system may be
      involved in the development of IgA nephropathy.

PMID- 8984225
TI  - Fibronectin production by human tubular cells: the effect of apical protein.
AB  - In progressive renal disease the degree of renal failure correlates with
      interstitial scarring and the rate of progression correlates with the degree of
      proteinuria. This has led to the hypothesis that proteinuria may cause
      interstitial scarring. Human tubular cells (HTC) grown on permeable membrane
      supports were characterized to be predominantly of proximal tubular origin. HTC
      produce the matrix protein fibronectin in a polarised fashion the ratio of
      basolateral to apical secretion being 2.9 +/- 0.2 at 48 hours. The addition of
      serum proteins (1.0 mg/ml) to the apical medium resulted in increased basolateral
      secretion of fibronectin, 2.62 +/- 0.23-fold after 24 hours and 2.40 +/- 0.16
      fold after 48 hours. Serum fractionation revealed that the stimulant to
      fibronectin production had a molecular weight 40 to 100 kDa. Platelet derived
      growth factor secretion was also stimulated to apical exposure to serum but
      transforming growth factor beta secretion was not detected. Addition of
      neutralizing anti-PDGF antibodies did not decrease fibronectin secretion. The
      activity of serum was not reproduced by albumin or by transferrin. Exposure of
      HTC to serum resulted in increased release of lactate dehydrogenase, suggesting a
      degree of cytotoxicity. This evidence could provide a mechanism for the link
      between proteinuria and interstitial scarring.

PMID- 8984219
TI  - Indicators of nutritional status in Turkish preschool children: results of
      Turkish Demographic and Health Survey 1993.
AB  - The Turkish Demographic and Health Survey (TDHS), conducted in 1993, provided
      data on the magnitude of malnutrition in a sample of 3152 preschool children from
      five geographical regions, and on its causal and conditioning factors. Stunting
      was found to be the dominant form of malnutrition (21 per cent). Altogether 10
      per cent of children were underweight and 3 per cent were wasted. There were
      urban-rural (16 v. 27 per cent, P < 0.001) and regional differences (highest in
      the East 38 per cent, lowest in the West and North 10 and 14 per cent,
      respectively; P < 0.001) in the rate of stunting. Among the most important
      conditioning factors were too early introduction of supplementary foods, mother's
      educational level, mother's work area, person who takes care of children while
      mother is at work, birth rank of children, birth spacing, number of children in
      an individual family, family size, and mother's welfare and hygiene indices. The
      need for an intersectoral approach for the development of remedial programs to
      reduce the effect of these factors and for periodic assessment of nutritional
      status of preschool children is stressed.

PMID- 8984229
TI  - Transgenic expression of VpreB-3 under the control of the immunoglobulin heavy
      chain enhancer and SV40 promoter.
AB  - Recently we isolated a novel gene, VpreB-3 gene from the cDNA library of a pre-B
      cell clone. This gene is selectively expressed in pre-B and bone marrow-derived B
      cell lines. Its products are associated with the immunoglobulin heavy (IgH) chain
      in pre-B cell line. In the present study, to address the role of VpreB-3 on B
      cell development, transgenic mice carrying the VpreB-3 gene under the control of
      the IgH enhancer and SV40 promoter were produced. The transgenic mice expressed
      the VpreB-3 gene in bone marrow and spleen at a high level compared with control
      mice. In the thymus, the expression of the transgene was also detected, although
      its level was low. Flow cytometry analysis revealed that the frequency of CD45R+
      and mu+ B cells were reduced in the bone marrow of 2 of the 11 transgenic mice
      and also reduced in the spleen of 1 of the transgenic mice. Furthermore, the
      results of a stromal cell-dependent B cell culture assay suggested that early B
      cell development, the differentiation from CD45R- B progenitor cells to CD45R+
      pro-B cells, was delayed in the bone marrow cultures of 3 of the 5 transgenic
      mice compared with the control mice. These results suggested that VpreB-3
      products may play some role in early B cell development at the stage of CD45R- B
      progenitor cells before the expression of surface mu chains.

PMID- 8984228
TI  - Adenine nucleotide metabolism of canine pancreas graft preserved by the two-layer
      (euro-collins' solution/perfluorochemical) method after reperfusion.
AB  - We have demonstrated that oxygenation of a pancreas during preservation by the
      two-layer method leads continued ATP production to maintain cellular integrity
      and produces an extended period of preserved pancreatic viability. In this study,
      we examined whether the pancreas grafts preserved by the two-layer method
      maintained adenine nucleotides pool as substrates for ATP synthesis before
      reperfusion and had the ability to synthesize ATP promptly and to recover energy
      charge potential (ECP) of the pancreas graft on reperfusion. After preservation
      by the two-layer cold storage method using EC for 48 hrs (group 1, n = 5), or
      simple cold storage in EC for 48 hrs (group 2, n = 5), canine pancreas grafts
      were autotransplanted. In control (group 3, n = 5), canine pancreas grafts were
      autotransplanted without preservation. Tissue adenine nucleotides concentrations
      were measured using high performance liquid chromatography (HPLC) before and
      after preservation, before reperfusion and after 1 hr- and 2 hr-reperfusion.
      Graft survival rates were 5/5, 0/5, and 5/5, in groups 1, 2 and 3, respectively.
      Total adenine nucleotides before reperfusion in group 1 was almost same levels as
      group 2 (7.41 +/- 1.47 vs 6.64 +/- 2.23 mumol/g dry weight, N.S.). Furthermore,
      ATP tissue levels in group 1 before reperfusion was 2.90 +/- 0.51 mumol/g dry
      weight and almost same levels as group 2 (2.03 +/- 0.68 mumol/g dry weight,
      N.S.). However, tissue ATP levels in group 1 after 2 hrs of reperfusion (6.71 +/-
      1.19 mumol/g dry weight) were significantly higher than group 2 (4.51 +/- 0.51
      mumol/g dry weight, P < 0.05), and almost same levels as control (group 3) (6.32
      +/- 1.62 mumol/g dry weight, N.S.). In addition, ECP in group 1 and 3 (0.90 +/-
      0.03 and 0.83 +/- 0.09, respectively) after 2 hr-reperfusion, were significantly
      higher than the value in group 2 (0.73 +/- 0.09, P < 0.01 and P < 0.05,
      respectively). It was clear that recovery of ATP on reperfusion was not depend on
      the residual nucleotides pool before reperfusion but the ability of the pancreas
      graft to recover tissue ATP levels and energy charge potential after reperfusion.
      We conclude that oxygenation of the pancreas graft during preservation by the two
      layer method allows for ATP synthesis which is essential in maintaining cellular
      integrity and leads to maintain the graft's ability to recover ATP levels and
      energy charge potential promptly after reperfusion. Consequently the pancreas
      graft survives.

PMID- 8984227
TI  - Blood pressure and blood glucose levels during a cross-over treatment of
      doxazosin, moduretic and amlodipine in hypertensive patients.
AB  - A cross-over study comparing the effects of doxazosin, moduretic and amlodipine
      on fasting blood glucose and blood pressure levels in 9 adult hypertensive
      Nigerians is presented. The results showed that doxazosin, moduretic and
      amlodipine were effective in reducing diastolic blood pressure and thus confirmed
      our previous observation of blood pressure reduction during the monotherapies of
      these antihypertensive agents. The study further indicated the effectiveness of
      doxazosin in the management of severe essential hypertension in Nigerian
      patients. Fasting blood glucose level significantly decreased during doxazosin
      treatment phase and increased during moduretic phase, while amlodipine treatment
      did not have any effect on blood glucose level. In conclusion, the cross-over
      study seem to confirm the effectiveness of doxazosin therapy and its antidiabetic
      effect in hypertensive patients. The effectiveness of amlodipine therapy in
      controlling blood pressure was also observed, but no effect on blood glucose
      level, while moduretic therapy has hyperglycemic effect despite its effectiveness
      in blood pressure control in African patients.

PMID- 8984231
TI  - The vasorelaxant effects of amrinone on neonatal rabbit thoracic aortic strips.
AB  - The present study was designed to compare the in vitro vasorelaxant responses to
      the bipyridine compound amrinone of prostaglandin F2 alpha (PGF2 alpha)
      precontracted aortic strips isolated from newborn (2 to 3 days old) and
      nonpregnant adult rabbits. Changes in forces were recorded isometrically. The
      effects of isoproterenol (beta-adrenergic receptor stimulator), forskolin (direct
      activator of adenylate cyclase) and theophylline (non-specific phosphodiesterase
      inhibitor) were also studied simultaneously. The vasodilator responses to
      amrinone, forskolin and theophylline in aortic strips from neonates were
      comparable to those of strips from adults. In contrast, the maximum relaxations
      to isoproterenol were significantly reduced in those from neonates as compared
      with those from adults, suggesting that beta-adrenergic receptor mediated
      responses are not fully developed in the neonate. The mean value for the ED50
      concentration (half the maximum response) for amrinone, isoproterenol and
      theophylline was 1.10 +/- 0.10 x 10(-4) M, 3.47 +/- 1.31 x 10(-8) M and 1.53 +/-
      0.10 x 10(-4) M, respectively, in the neonatal group and 1.17 +/- 0.19 x 10(-4)
      M, 3.75 +/- 1.11 x 10(-8) M and 1.75 +/- 0.06 x 10(-4) M, respectively, in the
      adult group; there were no significant differences between the neonatal and adult
      preparations. We concluded that the vasorelaxation produced by phosphodiesterase
      inhibitors demonstrated no maturation-related changes probably due to a stable
      cyclic AMP turnover through an unaltered phosphodiesterase activity in newborn
      and adult arteries.

PMID- 8984232
TI  - Proceedings of the 1st annual meeting of the Cardiopulmonary Bypass Consensus
      Panel. Napa Valley, California, October 19-21, 1994.

PMID- 8984230
TI  - Phylogenetic development of brain and brain sulci in primates.
AB  - The purpose of this study was to investigate the phylogenetic development of the
      cerebrum and cerebral sulcus in primates. The species selected were Macacus,
      Hylobates, Pan and Homo sapiens. These samples are classified as old world
      monkeys (Cercopithecidae), anthropoid apes (Pongidae), and Man (Hominidae).
      Although these four species divided up and went their separate ways from about
      the Oligocene era, the pattern of the cerebral sulci is similar. Of various
      cerebral sulci, the cingulate and calcarine sulci were selected, because they run
      on the medial surface of the cerebrum. The length of these sulci and fronto
      occipital (FO) length were measured by a "cotton-thread" method. With the
      increase of size (FO-length) and weight of the brain, these sulci became longer,
      but there were no significant differences in the ratio of the calcarine sulcus to
      the FO-length among these four species. On the contrary, the ratio of the
      cingulate sulcus to the FO-length in Pan and Homo sapiens was significantly
      higher than in the other species, indicating that this ratio becomes higher with
      the phylogenetic development. The results of the present study suggest that the
      ratios of these sulci to the FO-length can be used as good indices to assess the
      degree of the phylogenetic development of the brain.

PMID- 8984233
TI  - [The molecular pathology of RET protooncogene in families with multiple endocrine
      neoplasia type 2A].
AB  - BACKGROUND: Multiple endocrine neoplasm type 2A (MEN 2A) is an autosomal
      dominantly inherited disease characterized by medullary thyroid carcinoma,
      pheochromocytoma and hyperparathyroidism. Mutations have been identified in the
      extracellular domain of the RET proto-oncogen product (10q11.2) in MEN 2A
      patients. In each case a single base pair substitution results in replacement of
      cysteine with another amino acid. Most MEN 2A patients have mutations of codon
      634. PATIENTS AND METHODS: Sixty-five unrelated MEN 2A patients from seven
      families were studied. Polymerase chain reaction, segregation, sequence analysis
      and restriction enzyme digestion were performed. RESULTS: Of seven families, four
      had the TGC to TAC transition, two families the TGC to TGG transversion and one
      family the TGC to CGC transition in codon 634 of RET. CONCLUSIONS: We found all
      the mutations in codon 634. The characterization of MEN 2A mutations allows early
      and presymptomatic diagnosis in this syndrome.

PMID- 8984236
TI  - [Is the quality of semen decreasing?].

PMID- 8984234
TI  - [Heart disease in acromegaly. Study of 27 patients].
AB  - BACKGROUND: The patients with acromegaly have an increased propensity to develop
      cardiovascular complications. The aim of this study was to evaluate the most
      relevant clinic, echocardiographic and Holter recording findings in acromegaly
      and its correlation with the growth hormone (GH) levels and duration of the
      disease. PATIENTS AND METHODS: 27 patients with acromegaly were evaluated. The
      basal levels of GH and insulin-like growth factor 1 (IGF-1) were measured at the
      time of cardiological study and compared with the spontaneous GH secretion during
      12-24 hours previously studied. Echocardiogram was made using complete M-mode,
      two dimensional and spectral Doppler ultrasound mechanical system. Additionally
      an standard EKG and a Holter recording were performed during 24 hours. RESULTS:
      There was a strong correlation between basal levels of GH and integrated
      concentration of GH during the study of spontaneous secretion (r = 0.92; p <
      0.01). The prevalence of symptomatic cardiovascular complications in this study
      was 49%, including 3 patients who died for cardiovascular events. The
      echocardiographic study showed a high prevalence of left ventricular hypertrophy
      (66.7%), diastolic dysfunction (63%) and impaired systolic function (18.5%).
      There was no correlation between GH and IGF-1 levels and echocardiographic
      findings. Conversely the degree of hypertrophy was related to the duration of the
      disease and the presence of arterial hypertension. The diastolic function only
      was related with the presence of hypertension. We found supraventricular
      arrhythmic events and malignant premature ventricular complexes in 6 and 6
      patients, respectively. The EKG showed a high fiability to detect ventricular
      hypertrophy but no rhythm events. CONCLUSIONS: The high prevalence of
      cardiovascular complications in acromegaly, most of them asymptomatic, and its
      clinical relevance, advise the necessity to perform systematic cardiovascular
      evaluation in these patients.

PMID- 8984237
TI  - [Distal intrahepatic biliary tract diseases in adults: cholangitis and loss of
      ducts].

PMID- 8984240
TI  - [Acute hepatitis E in Spain].

PMID- 8984235
TI  - [Seroepidemiologic study of hepatitis C virus infection in a general population
      from the region of La Rioja, Spain].
AB  - BACKGROUND: To assess the prevalence of hepatitis C virus (HCV) infection in a
      general population and to identify risk factors for acquiring infection.
      POBLATION AND METHODS: A cross section of the general urban population of La
      Rioja aged between 14 and 65, was studied by choosing a random sample (n = 890).
      Serum samples were screened for HCV antibodies by second-generation enzyme-linked
      immunosorbent assays and recombinant immunoblot assays. We investigated the
      relationship between HCV serostatus and age, intravenous drug use, tattoos, blood
      transfusion, history of hepatitis, previous surgical operations, the
      administration of parenteral treatment and the number of sexual partners.
      RESULTS: The overall prevalence of anti-HCV antibodies was 2%. The logistic
      regression analysis confirmed a statistically significant association between
      anti-HCV positivity and intravenous drug use (OR = 169.67; CI 95%: 21.1
      1,364.75), exposure to a blood transfusion (OR = 10.41; CI 95%: 3.03-35.75);
      tattoos (OR = 9.04; CI 95%: 1.25-65.36), and male sex (OR = 5.35; CI 95%: 1.34
      21.42). However, that 38% of subjects had no risk factors for HCV infection.
      CONCLUSIONS: These results show a high proportion of people were found to have
      anti-HCV antibodies. The possible mode of infection in one third of these
      subjects is not known. In the half of these cases the infection was found have
      been acquired by an intravenous mechanism: blood transfusion or drug use.

PMID- 8984239
TI  - [A 46 years-old woman with multiple lymph node enlargement after a recent
      infection by Epstein-Barr virus].

PMID- 8984242
TI  - [Resistant tuberculosis in Madrid. Coinfection of tuberculosis and AIDS].

PMID- 8984241
TI  - [The Ardystil syndrome].

PMID- 8984244
TI  - [Health care management: coordination of health care assistance levels].

PMID- 8984243
TI  - [Resistant tuberculosis in Madrid. Coinfection of tuberculosis and AIDS].

PMID- 8984245
TI  - [The practice is closed! Threat of exclusion from the profession].

PMID- 8984238
TI  - [Respiratory disorders in movement disorders].

PMID- 8984248
TI  - [The driver's licence survey over the physician's head?].

PMID- 8984246
TI  - [Heart surgery in Sweden is sufficiently developed. Risk of expensive overuse].

PMID- 8984247
TI  - [Forget old findings on health inequality! Concentrate on research!].

PMID- 8984249
TI  - [Brighter prospects for patients with psychoses? New neuroleptics may improve the
      long-term prognosis].

PMID- 8984250
TI  - [For better prognosis of patients with psychoses. "Safety net" for patients with
      first-time psychosis].

PMID- 8984252
TI  - [The 150th anniversary of narcosis. An intoxicating, varied and noisy time].

PMID- 8984251
TI  - [The new antidepressive agents. Is it rational to prescribe drugs or a "mental
      brace"?].

PMID- 8984254
TI  - [France: a patient book will prevent vagabondizing of patients].

PMID- 8984253
TI  - [Varying assessment of "danger to life" in forensic reports].

PMID- 8984259
TI  - [IBM, money, calcium antagonists and bias].

PMID- 8984257
TI  - [A terminology system for health will be developed by Spri].

PMID- 8984261
TI  - [Reduced offer and shortage of time are the greatest problems of continuing
      education].

PMID- 8984258
TI  - [Can we trust the science and its megaphones?].

PMID- 8984260
TI  - [Elphobia of cell cultures?].

PMID- 8984263
TI  - [Everyone and nobody has the responsibility for the future of plasma products].

PMID- 8984255
TI  - [Inspections of continuing education: general practitioners are going to start
      and surgeons are testing the scrutiny of the AT-education].

PMID- 8984256
TI  - [The first Spur-inspections within medical gastroenterology and hepatology: the
      shortage of specialists is alarming].

PMID- 8984264
TI  - [Is the physician-in-chief's personal interpretation decisive in a HSAN trial?].

PMID- 8984265
TI  - [Finsam--a serious and well-functioning agreement].

PMID- 8984266
TI  - [Why are general practitioners employed by county councils more dissatisfied?].

PMID- 8984262
TI  - [The National Board of Health and Welfare must elucidate the role of standby
      duty].

PMID- 8984267
TI  - [The best antidepressive treatment: sensible pharmacotherapy and psychological
      readiness].

PMID- 8984269
TI  - [A case report. Fatal case of acute fluoxetine poisoning].

PMID- 8984268
TI  - [Hormones regulate eating behavior of the rat. Mechanisms of human food intake
      are probably the same].

PMID- 8984270
TI  - [Too little exposure to sun may cause vitamin D deficiency. Muslim women in
      Sweden are a risk group].

PMID- 8984271
TI  - [Management of acute tachycardia. Guidelines based on diagnostic flow schedule.
      Swedish Diagnostic Services].

PMID- 8984272
TI  - [Continuing compulsory care without medical reasons. Application of forensic
      psychiatry against the international ethics codex].

PMID- 8984273
TI  - [Egg return after fertilization in vitro. Frequency of pregnancies is the same
      with two eggs instead of three].

PMID- 8984274
TI  - [Disappointement, anger, bitterness, grief, hate...a lot of strong feelings
      behind reporting to the HSAN].

PMID- 8984276
TI  - ["Beneficial to shake up the system from time to time". The Norwegian
      prioritization is updated after 10 years].

PMID- 8984275
TI  - [Are depressive states "sick" or "healthy"? Correct therapy may be blocked by
      antidepressive agents].

PMID- 8984277
TI  - [A popular vote in California: don't change health services].

PMID- 8984279
TI  - [Informed consent is required for research with human participants. Ethical
      convention may inhibit the research].

PMID- 8984278
TI  - [What do spies and physicians have in common? Assessment Center is a new method
      for selection of physicians-in-chief].

PMID- 8984283
TI  - [MIC--for a unified terminology in health care].

PMID- 8984282
TI  - [Prolong the validity of prescriptions--a good proposal!].

PMID- 8984281
TI  - [Color duplex is the first choice in diagnosis of deep venous thrombosis].

PMID- 8984280
TI  - [What does the National Board of Health and Welfare do with continuing medical
      education?].

PMID- 8984285
TI  - [Bosnia-Herzegovina: support the reconstruction of psychiatry!].

PMID- 8984284
TI  - [Depression is also an existential phenomenon].

PMID- 8984287
TI  - [Biased drug information can distort a study].

PMID- 8984286
TI  - [Discuss human rights at the annual meeting of the medical society!].

PMID- 8984290
TI  - [Dysphagia. A common but hidden handicap].

PMID- 8984288
TI  - [A team for the sexually abused?].

PMID- 8984289
TI  - [Care of drug addicts administered by the county council is evaluated].

PMID- 8984293
TI  - [Ragnar Norrby on antibiotic resistance. Treatment of H pylori may result in a
      horror scenario].

PMID- 8984292
TI  - [An inquiry on quality of life among young patients with schizophrenia. Crisis
      intervention in the family].

PMID- 8984291
TI  - [Dysphagia unusually common at a department of otorhinolaryngology].

PMID- 8984300
TI  - [Pulsed dye laser against common bile duct calculi. Few complications and good
      results].

PMID- 8984296
TI  - [A case report. A pin in the appendix caused hepatic abscess].

PMID- 8984298
TI  - [Psychological aspects of trauma. Normal and pathological stress reactions].

PMID- 8984294
TI  - [Hyponatremia caused by diuretics in elderly women. Risk of adverse effects. Be
      careful with indications].

PMID- 8984297
TI  - [Carbon dioxide embolism in laparoscopic cholecystectomy. Early diagnosis reduces
      the risk of fatal complication].

PMID- 8984295
TI  - [Phytosterolemia is an uknown but serious disease. Xanthomatosis in childhood is
      a warning signal].

PMID- 8984299
TI  - [A study of post-traumatic stress reactions among war refugees based on medical
      records. A standard model may support the treatment].
AB  - A special project designed to aid Bosnian refugees in Stockholm County was
      initiated and funded by the County Council in February 1994. The present study, a
      joint endeavour involving the Bosnian Project, the Centre for Trauma and Torture
      Diagnostics, and the Red Cross Centre for torture victims, was designed to fulfil
      the following aims: To characterise the patient population in terms of social
      situation, trauma history, symptoms and treatment; To review accumulated
      experience at the three centres; To outline and discuss the treatment; and To
      suggest new avenues for further research concerning refugees and trauma. To
      obtain comparable material for this retrospective review of case records at the
      three centres, a special case chart format was adopted, covering pre-war and pre
      treatment information on general background, social situation, health status and
      medication, as well as trauma history, symptoms and treatment. Most patients
      reported good pre-war health, but at the time of the study exhibited manifest
      effects of trauma history; 95 per cent reported mental problems, and 39 per cent
      medical disease or physical disorders. These refugees were thus characterised by
      manifest post-traumatic stress symptoms and need of treatment. Despite their
      relatively short time in Sweden, almost all had permanent residence permits and
      fixed addresses. The absence of a comparable control group precluded comparison
      with other refugee or normal populations. The findings suggest the need of co
      ordination and co-operation between the special facilities available to refugees,
      and of a standardised format for case records.

PMID- 8984301
TI  - [The prioritization committee misses the target. The report forces the costs!].

PMID- 8984302
TI  - ["The amphetamine treatment helped my child". Is it time to reevaluate Swedish
      practice in hyperactivity syndrome?].

PMID- 8984303
TI  - [Natural drugs in a new Chinese database].

PMID- 8984304
TI  - [The licence drug policy of the Medical Drug Agency. Permitted use in special
      needs].

PMID- 8984305
TI  - [Reporting of incidents elucidate the shortcomings. The system was tested in
      pediatric intensive care].

PMID- 8984306
TI  - [An inquiry of interns in Linkoping about their wishes. More on leadership and
      examination techniques].

PMID- 8984307
TI  - Country profile: Germany.

PMID- 8984309
TI  - Surfactants and babies: slippery little things [new].

PMID- 8984311
TI  - Towards an epistemological view on medical informatics.

PMID- 8984308
TI  - Literature and medicine: the patient, the physician, and the poem.

PMID- 8984310
TI  - Professionalism in medical informatics.

PMID- 8984314
TI  - [A case-based and multi-media computer learning program on the topic of
      myocardial infarct, angina pectoris and mitral valve stenosis].
AB  - BACKGROUND: Principles in the field of cognitive psychology and problem-based
      learning together with recent progress in multimedia technologies are providing
      the basis for the development of case-based and computer-assisted learning
      systems. With reference to the information-overload of theoretical and factual
      knowledge in medical education these programs can be an efficient tool to satisfy
      the current need for new, practical, skill-related forms of knowledge transfer.
      METHODS: Apple-Macintosh Computers were selected to develop interactive,
      multimedia patient-simulations on mitral stenosis, angina pectoris and myocardial
      infarction. INSTRUCTIONAL AIM AND CONTENTS: The user acquires knowledge and
      skills about the leading symptoms, differential diagnoses, the use and analysis
      of laboratory examinations and the process of diagnostic reasoning while working
      through the computer-simulated cases. PEDAGOGICAL DESIGN AND CONCLUSION:
      Important pedagogical principles associated with computer-assisted learning were
      employed in the program. Clinical situations can be simulated repeatedly and for
      every student in an authentic manner. Therefore the program can serve as a
      preparation for and a supplement to practical clinical education. Compared to
      conventional teaching media the development of instructional multimedia software
      requires a tremendous amount of time and resources. Thus, controlled studies are
      important to objectify the overall advantages such programs can have.

PMID- 8984313
TI  - [Reduction of puncture-induced complications after heart catheterization by
      optimized compression technique despite reduced compression time. A prospective,
      duplex ultrasound and pressure controlled study].
AB  - The number of local complications after heart catheterization by transfemoral
      approach can be lowered by optimized compression technique in spite of shortened
      compression time. It requires a long-term (> 30 minutes) acute compression after
      removing the sheaths and stable pressure during the following compression period.
      To achieve this issue the deployment of a novel compression device is superior to
      the combination of manual compression and conventional pressure dressing. A
      pressure of 40 to 45 mmHg is sufficient and well tolerated. Local complications
      as pseudoaneurysms and arteriovenous fistulas are detected by duplexsonography
      with high sensitivity. Only about 50 percent of pseudoaneurysms are identified by
      physical examination in contrast to arteriovenous fistulas which are rarely
      missed because of their characteristic murmur. The early ultrasound-guided
      compression therapy is considered to be a safe treatment of pseudoaneurysms but
      is not effective in arteriovenous fistulas. Risk factors of local complications
      are high blood pressure, multiple arterial puncture and local-anatomical
      conditions. Compression-related factors are short acute compression (phi 14.3
      minutes) and loss of pressure during the following compression period.

PMID- 8984312
TI  - [Permissive effect of PTH on vascular wall hypertrophy of intramyocardial
      arteries in experimental renal failure].
AB  - BACKGROUND: Abnormalities in cardiovascular structure e.g. LV hypertrophy and
      thickening of vessels (elastic and peripheral arteries, veins) are hallmarks of
      renal failure. Among other hormones parathyroid hormone (PTH) has been shown to
      affect cardiac function and has also been identified at a permissive factor for
      the activation of the cardiac interstitium leading to myocardial fibrosis. The
      present study was designed to examine whether PTH was also permissive for
      intramyocardial arteriolar wall thickening in an experimental model of renal
      failure. MATERIAL AND METHODS: Sham operated or subtotally nephrectomized rats
      (SNX) were parathyroidectomized (PTX) and received either saline or rat 1,34 PTH
      by osmotic minipump. After perfusion fixation, intramyocardial arterioles were
      assessed using stereological techniques (wall thickness, wall/lumen ratio,
      minimal lumen diameter, length density). RESULTS: Wall thickness of
      intramyocardial arterioles was significantly higher in SNX than in sham-op
      controls. SNX-PTX animals receiving solvent did not differ from sham-op controls
      while SNX-PTX animals receiving PTH had increased values which were comparable
      with those of SNX. In addition, PTH treated animals showed signs of marked
      vascular smooth-muscle cell and endothelial cell activation. CONCLUSIONS: The
      data suggest that intramyocardial arteriolar wall thickening in experimental
      renal failure and probable changes of vessel architecture in renal insufficiency
      in general are dependent upon the permissive effect of PTH.

PMID- 8984315
TI  - [A patient with multiple intrapulmonary coin lesions].

PMID- 8984317
TI  - [Manifestation of iron deficiency].

PMID- 8984320
TI  - [Pneumocystis carinii and aspergillus pneumonia in immunosuppression in rapidly
      progressing glomerulonephritis of the anti-glomerular basement membrane type].

PMID- 8984316
TI  - [Explanatory models for HLA-b27 association of reactive arthritis as a paradigm
      for spondyloarthropathy].

PMID- 8984322
TI  - [Pro and contra adjuvant chemotherapy in colorectal carcinoma].

PMID- 8984319
TI  - [Long-term unrecognized foreign body aspiration as the cause of pleural
      effusion].

PMID- 8984323
TI  - [Clinical use of resorbable polymer mini-plates in mandibular fractures: a one
      year experience].
AB  - The authors describe their experience in rigid fixation of maxillo-facial
      fractures with resorbable plates made from poly-L-lactic acid. Seven cases are
      presented, with a one-year follow-up or longer. Plate resorption was evaluated by
      means of echographic examination, repeated every three months. All fractures
      healed well, with no complications. Finally, advantages and limits of the
      material are considered, as well as its future prospects and margins of
      improvement.

PMID- 8984321
TI  - [Health care economics evaluation of inpatient treatment of venous thrombosis
      with unfractionated heparin versus subcutaneous low molecular weight heparin at
      home].
AB  - BACKGROUND: An intravenous course of unfractionated heparin as initial treatment
      is the standard method to treat venous thromboembolism. Increasing scientific
      knowledge indicates that subcutaneous low-moleculare-weight heparin is just as
      effective and save as unfractionated heparin. A possible advantage of low
      moleculare-weight heparin is the cost saving potential in minor hospitalisation
      days. Both therapies will be continued for at least three months with an oral
      anticoagulative. Because hospitalisation belongs to the cost-intensivest factors
      in the German health care system the question of a health economic difference
      between both initial treatments raises. METHOD: We transformed published
      empirical evidences to the German health care system, valued them in a cost
      analysis for a hypothetical cohort of 100 patients and compared the outcome
      intertherapeutically. RESULT AND CONCLUSION: From perspective of sickness
      insurance fund as cost unit we estimate that a partial in hospital initial
      treatment with subcutaneous low-moleculare-weight heparin is more cost-effective
      than a total in-hospital initial treatment with unfractionated heparin.

PMID- 8984318
TI  - [Post-exposure drug prevention of HIV infection].

PMID- 8984324
TI  - [Clinical aspects of craniomandibular disorders. I. Analysis of a sample group of
      patients and diagnostic classification].
AB  - Data collected on 406 patients of both sexes, aged between 9 and 78 (mean age
      30.47) and suffering from algias and craniomandibular disorders, have been
      examined, in order to show the more frequent clinical variables and to improve
      the knowledge of the stomatognatic dysfunction, by characterizing diagnostic
      subgroups. The observed prevalence of the female sex and young adults is in
      agreement with the literature. Older subjects seem to accept more easily
      dysfunctional problems; the developmental age needs an active prevention. The
      data were similar to those of the previous researches, demonstrating that the
      trend of this disease is constant, during the last 15 years. The most frequent
      sign and symptoms were: joint noise, muscles tenderness, mandibular hypomobility,
      cephalalgia, earache. The classified, variously imbricated, pathologies were the
      muscular disorders (40.1%), the internal derangement (disk dislocations), (35.8%)
      and the inflammatory and degenerative (morpho-structural) changes (19.6%). The
      multifactorial aetiology was confirmed by investigating the main pathogenetic
      factors, which resulted: bruxism (35.9%), loss of vertical dimension (34.7%),
      postural problems (33%), mandibular entrapment (26.6%), facial asimmetry (26.1%).

PMID- 8984325
TI  - [Clinical aspects of cranio-mandibular disorders. II. Symptom profiles of
      subgroups].
AB  - The more frequent clinical variables of cranio-mandibular disorders in a sample
      of 406 patients of both sexes, aged between 9 and 78 (mean age 30.47), were used
      to classify the different pathologies of the stomatognatic dysfunction.
      Radiological imaging completed and improved the diagnostic assessment. The
      breakdown of the total patient population into diagnostic subgroups was:
      functional disorders, with a mainly myogenous component (19.7%); disk
      displacement with reduction (24.1%); disk displacement without reduction (11.7%);
      osteoarthrosis (10.8%); synovitis of various origin (8.8%); growth disorders
      (0.9%). A mixed group consisted of many patients displaying signs of internal
      derangement and contemporary pronounced muscular disorders (20.4%); finally some
      subjects did not show true disturbances of the masticatory system (3.6%).
      Considerable differences were found among the subgroups and the findings formed
      the basis of specific symptom profiles, that mainly considered the chief
      complaints as masticatory algia, earache, cephalalgia, migraine and neck and
      shoulders postural disturbances. The prevalence of specific pathogenetic factors
      confirmed the multifactorial aetiology and the need of a more directed choice of
      treatment.

PMID- 8984327
TI  - [Hypoplasia of enamel. A useful marker in the diagnosis of celiac disease in its
      subclinical form].
AB  - Oral cavity alterations are often indicative sign of chronic gastrointestinal
      disorders, such as malabsorption and malnutrition syndromes. The relationship
      between oral pathology and intestinal diseases is rarely a chance association.
      This prompted odontostomatological research to focus on the study of alterations
      of the oral cavity, hypotetical markers of intestinal disorders if they can be
      measured in terms of frequency and incidence, as a tool for the early diagnosis
      of the intestinal disease itself. This paper should be seen against this
      background since it examines the possible connection between celiac disease and
      the presence of oral alterations as an index of disease.

PMID- 8984326
TI  - [Clinical aspects of cranio-mandibular disorders. III. Principles of elective
      therapy].
AB  - The therapeutic approaches on 406 patients of both sexes, agent between 9 and 78
      (mean age 30.47) and suffering from cranio-mandibular disorders, have been
      analyzed, in order to evaluate the more frequent measures of treatment and to
      improve the management of pain and dysfunction of the stomatognathic system.
      Having confirmed the multifactorial aetiology, an individual treatment plan was
      worked out. Of the initial therapies, active gymnastics (63.58%), bland aspecific
      drugs (21.02%), assisted relaxation practices (7.17%) were of particular
      importance. As occlusion measures, stabilisation splint (44.61%) had precise
      instruction for use; in case of mandibular dislocation, a repositioning splint
      was constructed in articulator, in order to achieve a new therapeutic position
      (30.51%); sometimes, only a vertical dimension increase of previous prosthesis
      was made (14.35%). The specific symptom profiles of the diagnostic subgroups in
      which the sample was subdivided induced to adopt considerably different
      procedures, due to the basic pathology. The final therapy considered above all
      prosthetic (35.64%) and orthodontic (25.12%) rehabilitations, whether structural
      changes were necessary; moreover occlusal adjustment (5.64%); only few cases
      (2.05%) required a surgical consultation. A deliberate choice of conservative
      approach was evident in a remarkable number of patients (26.15%), treated in an
      absolutely reversible way.

PMID- 8984328
TI  - [Selenium and oral cancer. Review of the literature].
AB  - During normal cellular metabolism, free oxygen radicals are constantly generated.
      These are extremely toxic. However, they are rapidly eliminated by a series of
      metabolic steps, which involve certain enzymes such as superoxide dismutase,
      catalase and glutathione peroxidase (a selenium dependent enzyme). The toxic
      effect of free oxygen radicals has been suggested to have carcinogenic
      properties, and this hypothesis may be the link between low selenium levels and
      increased cancer morbidity. From this point of view a correct selenium
      concentration in the plasma may represent a form of chemioprevention. In fact,
      the concept of chemioprevention of carcinogenesis with inhibitory chemical
      compounds is particularly apropous to head and neck squamous cell cancer control,
      because the incidence of metachronous second primary tumours in surviving
      patients with oral cancer is very high.

PMID- 8984330
TI  - [Eosinophilic ulcer of the oral mucosa].
AB  - The eosinophilic ulcer is a rare lesion of the oral mucosa; it is a benign
      disease, the etiology and the pathogenesis are unknown. The authors describe a
      patient with eosinophilic ulcer of the oral mucosa. The clinical, pathologic and
      therapeutic aspects of this rare disease are discussed.

PMID- 8984329
TI  - [Paget disease of the jaws. Review of the subject. Clinical-therapeutic
      considerations].
AB  - Clinical and diagnostic findings of Paget's disease of the jaws are reported; up
      to date etiological and pathogenical hypotheses are presented. Laboratory data of
      increased P.A. as a marker of disease evolution is pointed out, particularly the
      relationship increasing hydroxyprolinuria, because the increase of a malignant
      transformation. Surgery, always modeling, is limited to cases of severe facial
      dysmorphosis associated or not with the local disturbance due to compression; in
      any case it is suggested to perform the surgery in the phases of inactivity of
      disease, to avoid local complications, such as hemorrhage a infection.

PMID- 8984335
TI  - Minimally invasive coronary-artery bypass surgery.

PMID- 8984332
TI  - Thrombolytic therapy in acute ischemic stroke.

PMID- 8984334
TI  - Thrombolytic therapy in acute ischemic stroke.

PMID- 8984333
TI  - Thrombolytic therapy in acute ischemic stroke.

PMID- 8984331
TI  - [A case of lingual agenesis].
AB  - Lingual agenesis is a rare anomaly caused by failed morphogenesis of the lateral
      lingual swellings during embriogenesis. Most reported cases have been part of
      oromandibular limb hypogenesis syndrome (OLHS). A case of lingual agenesis
      associated with micrognathia and alteration of the hands is reported.

PMID- 8984338
TI  - Placental-blood transplantation.

PMID- 8984337
TI  - Placental-blood transplantation.

PMID- 8984339
TI  - Placental-blood transplantation.

PMID- 8984336
TI  - Placental-blood transplantation.

PMID- 8984340
TI  - Energy expenditure in human immunodeficiency virus infection.

PMID- 8984342
TI  - Congenital malaria.

PMID- 8984343
TI  - The new health care game.

PMID- 8984347
TI  - Divided by a common language.

PMID- 8984341
TI  - Congenital malaria.

PMID- 8984346
TI  - The new health care game.

PMID- 8984348
TI  - Positional cloning of a global regulator of anterior-posterior patterning in
      mice.

PMID- 8984349
TI  - [Recurrent epistaxis: sometimes Rendu-Osler-Weber disease].

PMID- 8984344
TI  - The new health care game.

PMID- 8984350
TI  - [The treatment of pulmonary tuberculosis: shorter and with more potency].

PMID- 8984345
TI  - The new health care game.

PMID- 8984352
TI  - [Clinical testing of the treatment effect of interferon-beta Ia and Ib in
      multiple sclerosis].

PMID- 8984351
TI  - [Shorter treatment of pulmonary tuberculosis is only acceptable with at least 4
      drugs in the initial combination of tuberculostatic agents].

PMID- 8984353
TI  - [Proven tests in neurological diagnosis].

PMID- 8984354
TI  - [Quantification and evaluation of 5 neurological equilibrium tests in test
      subjects and patients].
AB  - OBJECTIVE: Quantification and evaluation of five neurological balance tests as
      part of the routine neurological examination in order to obtain objective test
      results for healthy individuals and several neurological patient groups. SETTING:
      Department of neurology, University Hospital Groningen, the Netherlands. DESIGN:
      Prospective, controlled study. METHODS: 220 subjects (113 healthy individuals and
      107 neurological patients) participated in a balance test investigation
      comprising gang board, Romberg's test, tandem gait, one-leg-stance, hopping.
      Tests were performed on a hopscotch (3 meters long, divided in 6 rectangles of 20
      by 50 cm) and using a stopwatch to register times and faults. RESULTS: All five
      quantified tests were feasible for healthy individuals. Up to the age of 70
      results gradually declined, above 70 a strong decline was observed. Patients with
      gait and balance disorders performed less well in all tests except the Romberg's
      test. CONCLUSIONS: Taking into account a strict standardisation of these five
      existing tests standard values were obtained for a fast and simple quantification
      of balance in the routine neurological examination, which can also be used to
      monitor progress. Especially the results obtained in tandem gait, one-leg-stance
      and hopping differ significantly between healthy individuals and patients. The
      gang board appears to be useful for quantifying serious balance disorders.
      Romberg's test is a specific test for the perceptual sensibility and does not
      belong in the routine neurological examination of balance.

PMID- 8984355
TI  - [Shortening of therapy duration in patients with pulmonary tuberculosis from 9 to
      6 months only justifiable on the basis of published data].
AB  - OBJECTIVE: To determine if in the Netherlands, just like in other countries, the
      treatment of pulmonary tuberculosis with adequately sensitive tubercle bacilli
      may be shortened from 9 to 6 months. DESIGN: Literature study. SETTING: Municipal
      Health Service, Nijmegen, the Netherlands. METHOD: The relevant literature was
      analysed, using the percentage of recurrences as the criterion. The study was
      restricted to patients with pulmonary tuberculosis in whom the diagnosis had been
      confirmed bacteriologically and in whom a human, normally sensitive tubercle
      bacillus had been isolated. The treatment schedule had to include at least
      isoniazid, rifampicin and pyrazinamide. There were no studies with treatment of 9
      months' duration. The studies with 6 months' treatment were selected on the basis
      of the predetermined criteria from among articles included in Medline in 1980
      1991. RESULTS: The treatment schedules of 6 months' duration (n = 44) from 25
      articles were suitable for analysis. Treatment for 6 months' resulted in a
      proportion of recurrences of tuberculosis of 2.4% (95%-confidence interval: 2.0
      2.8), with follow-up periods of 12 to 94 months after discontinuation of the
      treatment. Addition of streptomycin or ethambutol during the initial phase, self
      medication or controlled treatment, daily or intermittent treatment made no
      difference as regards the ultimate results. No comparison with the proportion of
      recurrences of 1% (0.2-2.9) after 9 month's treatment without pyranizamide was
      possible. A recent calculation of the number of Dutch nationals with recurrent
      tuberculosis resulted in a proportion of recurrences of 2.5 (1.8-3.2). The
      guideline adopted was that mentioned by the American Thoracic Society, a
      proportion of recurrences of < 5%. CONCLUSION: On the basis of the known
      percentages of recurrence, it could be decided in the Netherlands as well to
      shorten the duration of treatment from 9 to 6 months.

PMID- 8984356
TI  - [Drug resistance in Mycobacterium tuberculosis in The Netherlands].
AB  - OBJECTIVE: To determine magnitude, trend and specific features of the resistance
      problem. DESIGN: Descriptive. SETTING: Royal Netherlands Tuberculosis
      Association, The Hague, the Netherlands. METHODS: The data of the National
      Institute of Public Health and Environmental Protection concerning the prevalence
      of drug-resistant tuberculosis during the period 1990-1994 were analysed. Also,
      features of patients with and without drug resistance were compared (Dutch
      National Tuberculosis Register: cohort 1993). RESULTS: Isoniazid and streptomycin
      resistance were each observed in approximately 6% of susceptibility tests,
      showing no clear trend over the study period. Rifampicin resistance increased
      from 0% to 1.5% in 1994. In the 1993 patient cohort, 809 cases were analysed,
      showing resistant organisms in 103 (13%). The resistance group included 84 (82%)
      foreigners versus 387 (55%) among the 'sensitives' (p < 0.001). The percentages
      of (known) HIV infections were equal in both groups (5-6%). The percentage of
      isoniazid-resistance varied from 1.8% in Dutch patients to 7.8% in foreign
      patients. Recent immigrants and refugees waiting for official status were
      important risk groups for resistance (p < 0.005). Foreign tuberculosis patients
      defaulted more often from treatment than Dutch patients (p < 0.001). CONCLUSION:
      Drug-resistant tuberculosis in the Netherlands is mainly due to import of
      resistant strains. Transmission and further development of resistance within the
      country must be prevented.

PMID- 8984357
TI  - [Perianal streptococcal dermatitis in children].
AB  - Perianal dermatitis caused by Streptococcus pyogenes (beta-haemolytic Lance-field
      group A) was diagnosed in four children, three boys aged I, 6 and 8 years and a
      girl aged 2 years. Perianal itching in children is most frequently attributed to
      enterobiasis (Enterobius vermicularis); fissures due to scratching can complicate
      this situation. Perianal streptococcal dermatitis can effectively be treated with
      oral penicillin, in combination with local antibiotic application (fucidin,
      mupirocin).

PMID- 8984358
TI  - [Acute pulmonary edema caused by hydrochlorothiazide].
AB  - A 50-year-old woman who received a prescription for hydrochlorothiazide for
      'swollen ankles', developed respiratory distress due to acute pulmonary oedema
      within a few hours after she took the first dose. She was treated with artificial
      respiration during 3 days and with dopamine and circulatory volume suppletion.
      She recovered completely. Patient had stopped earlier use of hydrochlorothiazide
      because of respiratory discomfort. The described adverse effect is rare, but
      because of the high use of this drug it is important to recognize it.

PMID- 8984359
TI  - [History of healing; the treatment of tuberculosis in The Netherlands about
      1900].

PMID- 8984360
TI  - [The essence of the Law on Population Screening].

PMID- 8984361
TI  - [The essence of the Law on Population Screening].

PMID- 8984362
TI  - [Ventilation of patients in prone position in acute respiratory distress
      syndrome].

PMID- 8984363
TI  - [Pharmaco-economics and drug prices].

PMID- 8984364
TI  - [Acetylsalicylic acid and gastrointestinal hemorrhages: preferably a lower
      dosage].

PMID- 8984365
TI  - [The role of sentinel node biopsy in the treatment of patients with breast
      carcinoma].

PMID- 8984366
TI  - [Arthroscopic reconstruction using the Leeds-Keio ligament in anterior cruciate
      ligament lesions].

PMID- 8984367
TI  - [Additions to the consensus policy in the diagnosis and treatment of
      hyperlipidemia in clinical practice].

PMID- 8984368
TI  - [Arthroscopic reconstruction using the Leeds-Keio ligament following anterior
      cruciate ligament lesions in 200 patients].
AB  - OBJECTIVE: To establish the results of arthroscopic reconstruction of the
      anterior cruciate ligament with the Leeds-Keio ligament after a mean follow-up
      period of three years. DESIGN: Descriptive follow-up study. SETTING: Medisch
      Spectrum Twente in Enschede, the Netherlands. METHOD: The arthroscopic
      reconstruction has been carried out since 1988. Early in 1990 the prospective
      study was started. The patients were evaluated preoperatively according to a
      protocol. Postoperatively, follow-up consultations took place 3, 6 and 12 months
      after surgery and subsequently once every year. The results concerned the first
      204 patients (205 knees); 200 patients attended all follow-up consultations.
      RESULTS: In the early postoperative phase there were few complications (2%).
      After a short period of hospitalisation (mean 3.5 days), most of the patients
      were able to handle full weight-bearing quite soon (average 4.8 weeks). A total
      of 98% returned to their original jobs after a mean of almost 12 weeks, while 94%
      participated again in sporting activities after a mean of more than 15 weeks.
      Rupture or elongation of the Leeds-Keio ligament occurred in 9% of the patients,
      on average 18 months after surgery (6-32), and a partial rupture in three cases
      (2%). In 62% the rupture or elongation occurred after a new evident trauma.
      Subjectively 85% of the patients no longer complained of instability, objectively
      stability was found in 90%. Functionally a marked improvement in comparison with
      the preoperative situation was achieved: 89% had a good to excellent functional
      score (Lysholm score). At the last follow-up 92% were satisfied with their knee
      functioning. CONCLUSION: Arthroscopic reconstruction with the Leeds-Keio ligament
      leads to promising objective, subjective and functional results after a mean
      follow-up of three years, with few complications.

PMID- 8984369
TI  - [Identification of the sentinel node in patients with breast carcinoma].
AB  - OBJECTIVE: To investigate the hypothesis that lymphatic metastasis of breast
      cancer progresses in a sequential fashion, and whether the first lymph node on a
      direct drainage pathway (first-echelon node, sentinel node) can be identified in
      a mastectomy specimen. DESIGN: Descriptive analysis. SETTING: The Netherlands
      Cancer Institute (Antoni van Leeuwenhoek Hospital), Amsterdam, the Netherlands.
      METHODS: In 22 patients with clinically localized breast cancer and five with
      breast cancer and axillary lymphadenopathy, patent blue dye was administered
      preoperatively into the primary tumor. After mastectomy and axillary lymph node
      dissection, blue stained lymphatic channels were dissected down to the first
      draining lymph nodes. These sentinel nodes were removed from the specimen and
      examined separately for presence of metastatic disease. RESULTS: In 2/5 patients
      with palpable axillary metastases and in one patient with a tumour in the medial
      upper quadrant, no sentinel node was found. A total of 35 first-echelon nodes was
      identified in the 22 patients without palpable lymphadenopathy, on average 1.6
      nodes per patient (range: 1-4). In 10 of these patients, metastatic tumour was
      found in the sentinel nodes. In 6 of these 10 patients, no metastatic disease was
      detected in the remaining axillary nodes. Metastasis was never found in the other
      axillary nodes if the sentinel node was disease-free. CONCLUSIONS: Dissemination
      of breast cancer to the axillary nodes appears to occur in a sequential fashion.
      Patent blue dye drains from the tumour in the breast to the axillary lymph nodes
      in mammary cancer patients. These blue nodes can be identified in the surgical
      specimen.

PMID- 8984371
TI  - [Acute transit symptoms caused by spontaneous rupture of the esophagus].
AB  - A 44-year-old woman was admitted to our hospital with acute severe chest pain and
      dysphagia, without an assignable cause. Radiological investigation of the
      oesophagus with water soluble contrast revealed an intramural rupture.
      Conservative management led to complete recovery within eight days. Spontaneous
      intramural rupture of the oesophagus is a very uncommon disease requiring
      adequate differentiation from other more serious diseases in order to apply
      correct therapy.

PMID- 8984370
TI  - [Less axillary dissection necessary due to sentinel node biopsy in patients with
      breast carcinoma].
AB  - OBJECTIVE: To determine whether the sentinel node concept is appropriate in
      patients with breast cancer, notably whether the sentinel node can be identified
      after peritumoral injection of colloidal 99mTc albumin using lymphoscintigraphy
      or a handheld gamma probe in the axillary drainage area. DESIGN: Descriptive.
      SETTING: Academic Hospital Free University, Amsterdam, the Netherlands. METHOD:
      In 30 consecutive patients with T1 and T2 breast cancer lymphoscintigraphy was
      performed 2 and 18 hours after peritumoral injection of 40 MBq of colloidal 99mTc
      albumin injection. Focal accumulations in the axilla were registered and
      localized in vivo using a handheld gamma probe. All patients underwent axillary
      lymph node dissection. From each surgical specimen the sentinel node was isolated
      and examined histopathologically. RESULTS: In 28 of the 30 patients
      lymphoscintigraphy revealed at least one distinct focal accumulation in the
      axillary region after 2 and 18 h. In nine women more than one sentinel node was
      registered: two in six and three in three women. In all 28 patients the node was
      identified in the surgical specimen by gamma probe. In 19 of the 28 (67%) both
      the sentinel node and the axillary lymph nodes were without metastasis. Three
      patients had metastases both in the sentinel and in the other axillary nodes, and
      in 6 patients (21%) the sentinel node was the only node with metastasis.
      CONCLUSION: In the majority of breast cancer patients a sentinel node was
      identified after peritumoral injection of colloidal 99mTc albumin, and with a
      handheld gamma probe the node could be found in the surgical specimen. In none of
      the women metastasis was found in other lymph nodes if the sentinel node was
      unaffected.

PMID- 8984372
TI  - [Competence education, specifically the application of simulation].

PMID- 8984373
TI  - [Costs of diagnosis and treatment for pulmonary embolism lower due to application
      of consensus strategy].

PMID- 8984374
TI  - [No uniformity in radiodiagnosis and recommendations by Dutch neurologists in
      patients with minor brain injuries].

PMID- 8984375
TI  - [Crib death in secondary prone position; characteristics and prevention].

PMID- 8984376
TI  - [All lung tumors are not the same].

PMID- 8984377
TI  - [Riluzole treatment in amyotrophic lateral sclerosis].

PMID- 8984378
TI  - [The complement system and clinical effects of its disorders].

PMID- 8984379
TI  - [Fulminant liver insufficiency and the possible role of intracranial pressure
      monitoring, also in children].

PMID- 8984380
TI  - [Precordial and transesophageal echocardiography in the diagnosis and treatment
      of patients with atrial fibrillation].

PMID- 8984381
TI  - [No effects of the educational campaign among family physicians on Toxocara
      infections in humans].
AB  - OBJECTIVE: To evaluate the effect on general practitioners of an educational
      campaign about Toxocara and toxocariasis in man. DESIGN: Descriptive. SETTING:
      General practices in the Netherlands. METHOD: Telephone interviews of two groups
      of general practitioners before (n = 135) and 6 months after (n = 105) an
      educational campaign in 1993. RESULTS: No significant difference in knowledge
      concerning Toxocara and toxocariasis was observed in the two interviews. From the
      general practitioners interviewed, 44% considered Toxocara infections a zoonosis
      and 13-15% knew that 90-100% of puppies are infected. The clinical symptoms that
      were mentioned, agreed very little with the actual symptoms of toxocariasis.
      CONCLUSION: The knowledge of this important zoonosis was in general inadequate
      and the campaign to improve the awareness failed.

PMID- 8984382
TI  - [Transmission of sensitive and resistant strains of Mycobacterium tuberculosis in
      The Netherlands, 1993-1995, studied by means of DNA fingerprinting].
AB  - OBJECTIVE: Determination of the contribution of recent transmission of both
      sensitive and drug-resistant Mycobacterium tuberculosis strains to the number of
      tuberculosis cases in the Netherlands. DESIGN: Descriptive study. SETTING:
      National Institute for Public Health and Environment, Bilthoven, the Netherlands.
      METHODS: Since 1993 all isolates of M. tuberculosis in the Netherlands are sent
      to the national reference laboratory for surveillance purposes. The strains with
      IS6110 DNA fingerprint, isolated from January 1993 to July 1995, were analysed
      for clustering of DNA patterns (clustering of identical DNA patterns was assumed
      to represent recent transmission of tuberculosis). A transmission index was
      calculated from the ratio of the number recently infected tuberculosis patients
      and the number of source patients. RESULTS: Among 2,217 M. tuberculosis isolates,
      1,313 unique DNA fingerprints were observed, while 264 DNA patterns occurred more
      than once. 904 (41%) DNA fingerprints were part of a cluster of identical
      fingerprints. The mean cluster size was 3.42. The 232 resistant strains showed
      significantly less clustering (33% versus 42%, p < 0.02) and a smaller
      transmission index (0.27 versus 0.42, p < 0.02) compared with sensitive strains.
      CONCLUSION: Recent transmission contributes to the magnitude of the tuberculosis
      problem in the Netherlands. The epidemiological situation would, however, lead to
      gradual elimination of the disease were it not for introduction of tuberculosis
      from other countries. Transmission of resistant strains is relatively limited.
      Micro-epidemics caused by resistant M. tuberculosis strains were not observed.

PMID- 8984383
TI  - [Border-crossing source tracing in tuberculosis via DNA fingerprint technique].
AB  - OBJECTIVE: Description of the value of modern DNA analysis ('restriction fragment
      length polymorphism'; RFLP) as a method for mapping tuberculosis transmission.
      DESIGN: Descriptive. SETTING: Social Health Service Noord-Friesland, the
      Netherlands. METHOD: A large-scale tuberculosis investigation was conducted in
      Harlingen in 1993 when a 2,5 year old patient with tuberculous meningitis was
      reported. Source tracing and contact tracing extended from Harlingen to the west
      of the Netherlands and even abroad. Modern DNA analysis (RFLP) was used to map
      the tuberculosis transmission. RESULTS: A total of 6519 persons were screened and
      276 infected people were identified, of whom 49 were suffering from active
      tuberculosis. RFLP analysis showed in 27 of them a 'Harlingen' type Mycobacterium
      tuberculosis DNA pattern identical to that of the index patient. The source
      patient was finally traced in England. By the end of 1994 3 more patients were
      found with the same DNA pattern; their relation with the source patient and the
      outbreak of tbc remained unrevealed. CONCLUSION: The Harlingen outbreak was
      extensive and characterized by time-consuming source tracing. Modern DNA analysis
      proved to be a very useful instrument in identifying the source case.

PMID- 8984384
TI  - [Transmission of multiresistant tuberculosis in a Dutch hospital].
AB  - Nosocomial transmission of multiresistant tuberculosis in the Netherlands is
      described for the first time in this article. It was detected by systematic
      country-wide DNA-fingerprinting. By the time the contact case (a man aged 35)
      developed disease he was residing in another part of the country. Contact
      investigation by the Municipal Health Services involved revealed that the (HIV
      negative) contact case had been in contact with the index case (a man aged 27)
      during hospitalisation two years earlier. An analysis of the infection control
      measures applied, showed that inadequate treatment, early discharge from
      isolation and lack of bacteriological control (no sputum conversion documented)
      led to this hospital transmission.

PMID- 8984385
TI  - [Results of screening for HIV antibodies in pregnant women in Amsterdam reference
      stations, 1988-1995].
AB  - In order to determine the prevalence of HIV in the general heterosexual
      population of Amsterdam, 16,709 pregnant women attending two hospitals and one
      maternity clinic in the period 1988-1995 were asked to undergo a HIV test, of
      whom 15,276 gave informed consent (91.4%). Pregnant women with a risk of HIV
      infection were possibly overrepresented in those who refused. The overall HIV
      prevalence in 1988-1995 was 0.28% and showed no significant differences over the
      years. In women with a known risk factor for infection the prevalence was
      240:10,000, in those without 5:10,000. Whereas intravenous drug use was the most
      probable cause of infection before 1993, since then it was observed in only 2/20
      of the HIV positive pregnant women. Heterosexual transmission appears to be
      increasing.

PMID- 8984386
TI  - [Thromboembolic complications in central venous catheters].

PMID- 8984387
TI  - [The role of sentinel node biopsies in the treatment of patients with breast
      carcinoma].

PMID- 8984388
TI  - [The role of sentinel node biopsy in the treatment of patients with breast
      carcinoma].

PMID- 8984389
TI  - [Statement by the Board for Evaluation of Drugs].

PMID- 8984390
TI  - [Blunt testicular trauma].

PMID- 8984391
TI  - [Conservative or surgical treatment of ankle fractures?].

PMID- 8984392
TI  - [Is heart transplantation in The Netherlands only for the lucky few?].

PMID- 8984393
TI  - [Nursing and caregiving personnel; qualified for the future].

PMID- 8984394
TI  - [Neurodegenerative disorders and the role of trinucleotide repeat expansion. I.
      The diseases].

PMID- 8984395
TI  - [Neurodegenerative disorders and the role of trinucleotide repeat expansion. II.
      Molecular genetics].

PMID- 8984396
TI  - [Neurodegenerative disorders and the role of trinucleotide repeat expansion. III.
      Molecular pathophysiology].

PMID- 8984397
TI  - [Differentiated protocol for the conservative/surgical treatment of ankle
      fractures in children].
AB  - OBJECTIVE: Evaluation of the long-term results of protocolled treatment of ankle
      fractures in childhood. SETTING: St Elisabeth Hospital, Tilburg, the Netherlands.
      DESIGN: Retrospective long-term follow-up study. METHOD: All 78 children with an
      ankle fracture and an open epiphyseal plate in the period 1985-1989 were treated
      according to a protocol which specified the indications for conservative or
      surgical therapy depending on the particular fracture type according to Salter
      and Harris. After a median follow-up period of 3.42 years (range: 2.08-7.67
      years) in 48 patients the treatment results could be evaluated in 92% of these
      patients. Thirty patients had an isolated fracture of the distal part of the
      fibula. RESULTS: A clinically 'good' or 'excellent' result was achieved in 100%
      of the patients, and an 'excellent' result in 68%. CONCLUSIONS: Growth
      disturbances after an ankle fracture in children with an open epiphyseal plate
      can now be restricted to the very rare fractures with severe damage to the
      germinative layer of the epiphyseal plate. In general, conservative treatment
      should be used in Salter and Harris I and II fractures and operative treatment in
      displaced Salter and Harris III and IV fractures.

PMID- 8984398
TI  - [Differentiated protocol for the conservative/surgical treatment of ankle
      fractures in adults].
AB  - OBJECTIVE: Evaluation of the long-term results of protocol treatment of adult
      patients with ankle fractures. SETTING: St Elisabeth Hospital, Tilburg, the
      Netherlands. DESIGN: Retrospective long-term follow-up study. METHOD: All
      patients (n = 579) with an ankle fracture (580 fractures) in the period 1985
      1989, who had not died soon after the injury and in whom the morbidity was not
      caused mainly by other conditions (n = 30) were treated according to a protocol
      which specified the indications for conservative or surgical therapy depending on
      the particular fracture type. After a median follow-up period of 5 years (range:
      2.25-8.17 years) the treatment results could be evaluated in 92% of the patients.
      RESULTS: Clinically "good' or "excellent' results ranging from 79-90.5% types A,
      B and C fractures (according to the Swiss Arbeitsgemeinschaft fur
      Osteosynthesefragen) were achieved. CONCLUSIONS: A broad indication for
      conservative, even functional (tape bandaging) treatment and restricted use of
      implants during osteosynthesis appear justified considering the results obtained.

PMID- 8984399
TI  - [What do reviewers look for in 'original articles' submitted for publication in
      the Nederlands Tijdschrift voor Geneeskunde?].
AB  - OBJECTIVE: To determine to what extent reviewers of the Nederlands Tijdschrift
      voor Geneeskunde (Dutch Journal of Medicine, NTvG) use specific criteria when
      reviewing original articles. DESIGN: Descriptive. SETTING: Editorial office of
      the NTvG. METHODS: From 21 October 1993 to 1 March 1994, 89 original research
      manuscripts were received. Of these, 60 (67%) were submitted to reviewers. Each
      manuscript was sent to a second reviewer, with the same expertise, as well. On
      the basis of two checklists with a total of 16 quality elements, the manuscripts
      were analysed and compared with the chief editor's judgement. The results of each
      individual referee were correlated with his year of graduation. The duration of
      the peer review procedure was established. RESULTS: The reviewers of the NTvG
      responded to 46% of the explicit questions from the editors (list one), while
      they commented upon 43% of the criteria in the second implicit list. There was no
      relation with the year of graduation. Approximately 12% of the flaws in the
      manuscripts, as assessed by the editor, were missed. About 42% of the correct
      elements in the manuscript were not mentioned in the evaluation. The interrater
      agreement between paired reviewers was 0.26 (kappa); on average 10.4 of the 16
      checkpoints were mentioned or not by both. Peer review took 41 days on average.
      CONCLUSION: Only a small fraction of the flaws in a manuscript were missed by the
      reviewers. Peer review is reasonably uniform at the NTvG, but would probably
      benefit from standardization.

PMID- 8984400
TI  - [Successful heart transplantation in long-term ventilated patients].
AB  - Cardiac transplantation was carried out in three men, aged 50, 34 and 36 years
      with severe chronic heart failure. They did not completely meet the Dutch
      criteria, notably with respect to absence of contraindications and the
      requirement of thorough screening. The treatment was successful.

PMID- 8984401
TI  - [Notification of potential side effects of selective serotonin reuptake
      inhibitors in Belgium and The Netherlands].

PMID- 8984402
TI  - [Repatriation of patients via airplane: think before beginning].

PMID- 8984403
TI  - [Repatriation of patients via airplane: think before beginning].

PMID- 8984404
TI  - [Palliative cryosurgery in rectum carcinoma].

PMID- 8984405
TI  - [Patient-oriented education in family practice within medical education:
      curriculum of the Rijksuniversiteit Limburg].

PMID- 8984406
TI  - [Respiratory insufficiency: calculate the cause].

PMID- 8984407
TI  - [How poorly fare our children?].

PMID- 8984408
TI  - [Vegetative state].

PMID- 8984409
TI  - [Bone induction using bone growth factors: bone morphogenetic proteins].

PMID- 8984410
TI  - [Bisphosphonates in osteoporosis; a reevaluation].

PMID- 8984411
TI  - [Change in the management of patients with type II diabetes in The Netherlands].

PMID- 8984412
TI  - [Potential role for family physicians in pushing back age-related impairment:
      hearing and vision disorders, incontinence and arthrosis].
AB  - OBJECTIVE: To determine which age-related disorders lend themselves for screening
      followed by intervention in general practice. SETTING: Department of General
      Practice Medicine, University of Leiden. DESIGN: Descriptive. METHODS: This study
      concerned eight frequent age-related disorders: auditory and visual disorders,
      cognitive limitations, vertigo, incontinence, prostate symptoms, osteoarthritis
      and depressive symptoms. Four criteria (diagnostic possibilities, therapeutic
      possibilities, suitability of general practice for screening and intervention,
      the benefit of the programme to the elderly) were applied to selected literature
      (from Medicine and the electronic article files of the Nederlands Tijdschrift
      voor Geneeskunde (Dutch Journal of Medicine) and of Huisarts en Wetenschap (GP
      and Science) to find out whether screening followed by intervention appeared
      useful. RESULTS: With regard to three disorders (auditory and visual disorders
      and incontinence) it appeared possible to reduce the impairments caused by them,
      while in osteoarthritis, screening and intervention might lead to better
      mobility. CONCLUSION: With reference to recent literature, it appears
      theoretically possible to reduce the impairments caused by auditory and visual
      disorders, incontinence and osteoarthritis.

PMID- 8984413
TI  - [Causative role of infections with viruses or atypical pathogens in acute
      exacerbations of chronic bronchitis less frequent than expected].
AB  - OBJECTIVE: To determine the prevalence of viruses and atypical pathogens as
      causes of acute severe exacerbations of chronic bronchitis. DESIGN:
      Retrospective. SETTING: University Hospital Utrecht, the Netherlands. METHODS: In
      4 studies with 305 patients with severe type-1 exacerbations (increase of
      dyspnoea, of sputum volume and of sputum purulence) serological tests for viral
      and atypical pathogens were performed. RESULTS: Positive serology for viral
      infections was seen in 18 (5.9%) patients and for the atypical pathogens in 12
      (3.9%) patients. CONCLUSIONS: Since viruses and atypical pathogens are the cause
      of the exacerbation in only few cases, clinical signs can be used in decision
      making whether or not to prescribe antibiotics in acute exacerbations of chronic
      bronchitis.

PMID- 8984414
TI  - [Bedwetting by Dutch, Surinam, Moroccan and Turkish 3-4, 5-6, and 11-12-year-old
      children].
AB  - OBJECTIVE: To investigate whether ethnic origin is related to the prevalence of
      bedwetting among children and how parents handle bedwetters. DESIGN: Descriptive
      study. SETTING: Department of Youth Health Care in Amsterdam, the Netherlands.
      METHOD: Parents of children who attended a child health centre in 1992/1993 were
      interviewed using a questionnaire. A total of 1506 children aged 3-4, 2422 aged 5
      6 and 2081 aged 11-12 years participated in the study. RESULTS: The prevalences
      of bedwetting were 24.6%, 15.7% and 5.4% at 3-4, 5-6 and 11-12 years of age
      respectively. Moroccan and Turkish 3-4-year-olds wet their beds just as often as
      Dutch children, Surinamese 3-4-year-olds less often. However, Surinamese,
      Moroccan and Turkish school children wet their beds more often than their Dutch
      classmates. For Dutch children the prevalence of bedwetting at the age of 5-6 was
      clearly lower than at the age of 3-4, in contrast with Surinamese, Moroccan and
      Turkish children. Non-Dutch bedwetters were rewarded less often for a dry night
      and punished more often for a wet night than Dutch bedwetters, even at the age of
      3-4. CONCLUSION: Bedwetting by school children still occurs often, and more often
      among non-Dutch than among Dutch children. Possibly, differences between Dutch
      and non-Dutch parents in the ways they deal with bedwetting plays a part.
      Appropriate information and support of (especially non-Dutch) parents of young
      children can perhaps reduce the prevalence of bedwetting at later ages.

PMID- 8984415
TI  - [A tropical ulcer; cutaneous diphtheria].
AB  - A 43-year-old woman, born in the Netherlands, developed ulcers on her left foot
      during a holiday in Gambia and Senegal. She had been bitten bij insects. The
      ulcers were caused by Corynebacterium diphtheriae. The patient was treated with
      antibiotics and recovered fully. A grey pseudomembrane covering the ulcer is a
      characteristic feature of cutaneous diphtheria. The treatment is with antibiotics
      and, after toxin tests have indicated that the bacterium is toxigenic, with
      antitoxin. In some cases screening of social contacts is advised.

PMID- 8984416
TI  - [Geriatrics in The Netherlands. I. Development].

PMID- 8984417
TI  - [Geriatrics in The Netherlands. II. Networks geriatrics].

PMID- 8984418
TI  - [Is heart transplantation only for the 'lucky few' in The Netherlands?].

PMID- 8984419
TI  - [Aspects of pica in adult psychiatric patients].

PMID- 8984420
TI  - Microalbuminuria in Hypertension.

PMID- 8984421
TI  - The perceived effect of stressors on marital satisfaction among civilian wives of
      enlisted soldiers deployed to Somalia for Operation Restore Hope.
AB  - Nearly 400 spouses of enlisted soldiers who had deployed to Somalia as part of
      Operation Restore Hope in late 1992 and early 1993 were surveyed in July/August
      1993. Their reported post-deployment and retrospective pre-deployment marital
      satisfaction was predicted as a function of four potentially stressful events or
      conditions: experiencing a pregnancy during deployment, experiencing loneliness,
      experiencing the death of a close friend or relative, and/or having problems
      communicating with one's spouse. Pre-deployment marital stability was used as a
      control variable. Results from multivariate analyses of variance suggest that the
      effects of various difficulties during a brief deployment are less stressful, at
      least in terms of their impact on marital satisfaction, than is often assumed,
      even for marriages that might be considered "at risk" in terms of low marital
      stability.

PMID- 8984422
TI  - [Recommendations on the structural characteristics of the intensive care unit.
      SIAARTI Study Group for the Safety in Anesthesia and Intensive Care].

PMID- 8984423
TI  - [Sedation, combined anesthesia, and total intravenous anesthesia (TIVA) with
      propofol in the pediatric surgical patient].
AB  - Total intravenous anaesthesia (TIVA) has recently obtained a wide diffusion in
      paediatrics, thanks to the pharmacological properties of propofol. The authors
      make a review on sedation, combined anaesthesia and Tiva in paediatric
      anesthesia, particularly on propofol and its characteristics. They describe the
      practical use of TIVA with recent knowledge in this field.

PMID- 8984424
TI  - [Monitoring in pediatric anesthesia].
AB  - The monitor plan should be tailored to the individual patient, keeping in mind
      two main factors: the patient condition and the type of surgery to be performed.
      The advances in technology have greatly widened the scope of useful information
      to the physician, though direct contact and observation of the patient still
      remains the grounding of sound monitoring. In paediatric age the monitoring of
      breathing is of paramount importance since the high oxygen consumption-FRC oxygen
      supply ratio make children particularly prone to develop hypoxaemia very quickly.
      The minimal monitoring standard should include pulse oxymeter, a capnograph, an
      ECG monitor, oscillometer for noninvasive blood pressure measure and in the
      infant and young child a thermometer probe. For major surgery, in addition to
      mandatory monitoring many other physiological variables are checked frequently.

PMID- 8984425
TI  - [Myorelaxants in pediatric anesthesia].
AB  - The response to muscle relaxants and the dose required change during growth from
      birth to adolescence. Some physiological factors such as development of
      neuromuscular junction, the different distribution of the muscle fibres, and the
      extracellular fluid compartment affect the non depolarizing muscle relaxant
      (NDMR) ED 95, onset time and recovery time. Infants under 1 year of age are more
      sensitive to the NDMR and need less drug; children aging more than 1 year are
      more resistant and need a larger amount of drug; the reversal of the
      neuromuscular blockade before extubation, is extremely important especially in
      infants with long-acting agents.

PMID- 8984426
TI  - [Artificial ventilation in children during anesthesia].
AB  - The authors describe the advantages and disadvantages, the indications and
      benefits on gas exchange as a result of mechanical ventilation during
      anaesthesia. The two models of ventilation most commonly used have been analyzed:
      pressure ventilators and volume preset ventilators. The former are used only in
      cases of short-term anaesthesia or when volume ventilators are not available.
      Both the most appropriate settings and ventilatory modes have been discussed
      regarding different paediatric ages. Particular attention has been given to the
      oxygen concentration in the ventilated gases (oxygen toxicity > 40%) and to
      barotrauma connected with high peak pressure (> 30 cm H2O). The authors suggest
      the type and caliber of endotracheal tube and the tidal volume for paediatric
      ages.

PMID- 8984427
TI  - [Infusion constituents in pediatric anesthesia].
AB  - A suitable perioperative fluid therapy during paediatric anaesthesia presupposes
      a valuation of renal function and the preoperative fluid and electrolyte
      imbalance, a precise knowledge of fluid requirements and the physiological stress
      responses to surgery in different paediatric groups. Fluid administration must be
      suited to the pathology of the patients and surgical approach. It must replace
      the deficits from the preoperative status (including fasting), provide
      maintenance fluid and correct intraoperative translocated fluids and blood loss.
      Fluid management requires reduced hypotonic solution in order to prevent
      hyponatremia and avoid excessive amount of glucose which can be harmful. In order
      to prevent the dangers from blood transfusions you need to estimate the
      intraoperative loss and follow the "acceptable hematocrit" values. Rational
      intraoperative fluid management reduces perioperative morbidity and mortality.

PMID- 8984428
TI  - [Medium- and long-term use of central venous catheters in pediatrics. Personal
      experience].
AB  - From January 1992 to October 1994, 74 central venous catheters were inserted, in
      the University Hospital of Rome: Polyclinic Umberto I - "La Sapienza", in 62
      paediatric patients (15.17 +/- 1.64 years old), admitted to the paediatric
      surgery division. The authors used a large amount of CVC: totally implanted
      devices (34 Groshong, 7 Broviac, 2 Hickman, 3 Port) and percutaneous catheters
      (28 Arrow). The choice of the infusional devices has been influenced by the
      length of the treatment, the primitive disease, the age and the size of the
      patient. The authors used totally implanted devices in paediatric patients
      undergoing chemotherapeutic and nutritional therapies. External central venous
      access devices were used in patients undergoing central catheterization lasting
      less than two months. The subclavian vein has been used as venous access in
      patients weighing > 5 kg, the internal jugular vein in < 5, kg patients. This
      work reports the early (PNX, hematomas, arterial access) and the long term
      complications (infections, accidental unthreading, occlusions and dislocations).
      We can say that the medium and long last term CVC is well tolerated and accepted
      in paediatric patients too, for antineoplastic, nutritional and infusion
      therapies.

PMID- 8984429
TI  - [Variability of the morphological traits in the blood-sucking black fly Odagmia
      caucasica (Diptera: Simuliidae)].
AB  - Eleven morphometric and four qualitative features of larvae, as well as 6
      morphometric parameters of pupae of Odagmia caucasica, which had been collected
      in 5 geographically remote regions of Armenia, have been studied. In this work
      besides absolute values of features we have used their ratios (indices) that
      shows forms and proportions of different organs. It was found, that larvae taken
      from Bzhni and Getashen had asymmetry of bilateral characteristics and that there
      were differences in the level of morphometric features variability; the latter
      fact is connected with sex and phase of the insect. Study of chronological
      variability of populations from Bzhni, Getashen and Martuni has revealed
      differences in the nature of distribution of features. It was shown that the rate
      of differentiation between geographically isolated populations fluctuated in the
      range from 20 (Getashen) to 33% (Amassiya). Differences in the qualitative
      alternative features and in the rate of microsporidium infection distinguish the
      differentiation of populations from Bzhni and Amassiya, which is caused by
      anthropogenic factor in Bzhni and by isolating landscape barrier in Amassiya.
      Species-specific morphometric features were discovered; these were the indices of
      proportions of larva ventral sclerite and of pupa respiratory filaments.

PMID- 8984430
TI  - [The life cycle and fine morphology of the embryophores in Microsomacanthus
      paraparvula (Cestoda: Hymenolepididae), a parasite of diving ducks in Chukotka].
AB  - It was found out, that the cestode Microsomacanthus paraparvula Regel, 1994 being
      a common parasite of diving ducks in Chukotka uses a caddisfly Grensia praeteria
      (Trichoptera) as an intermediate host in its life cycle. Mature fragments of the
      cestode have been collected from droppings of the experimentally infected
      nestling of the kittiwake Rissa tridactyla (non-specific host) and used for the
      fine morphology study of embryonic shells and for an infection of intermediate
      hosts.

PMID- 8984431
TI  - [The biorhythmology of primary and superinvasive opisthorchiasis. The seasonal
      variability in the relative mass of the parenchymatous and lymphoid organs in
      golden hamsters].
AB  - 600 Golden Hamsters were divided into 3 groups: 1--free from opisthorchis
      invasion, 2--once infected, 3--repeatedly infected. Seasonal variability of
      liver, portal and mesentery lymph node and adrenal gland relative mass was
      investigated in winter, spring and autumn. Diurnal stereotype variability of
      parenchymatous and lymphoid organ relative mass is associated with a season and
      invasion number, and in a considerable degree is reflected in the meaning of
      average diurnal index.

PMID- 8984432
TI  - [Fleas of Insectivora in western and central Siberia].

PMID- 8984433
TI  - [Synonymy of generic and homonymy of species names for palearctic black flies
      (Diptera: Simuliidae)].
AB  - Some changes in the synonymy of several generic names are given (Ahaimophaga
      Chubareva, 1978 = Helodon Enderlein, 1921; Haimophaga Rubzov et Yankovsky, 1984 =
      Helodon, Enderlein, 1921; Astega Enderlein, 1930 = Cnephia Enderlein, 1921;
      Boreosimulium Rubsov et Yankovsky, 1982 = Hellichiella Rivosecchi et Cardinali,
      1975; Odagmia Enderlein, 1921 = Simulium Latreille, 1802; Gnus Rubsov, 1940 =
      Simulium Latreille, 1802). For 18 preoccupied species names (junior homonyms) the
      new replacing names are proposed (alajensis Rubzov. 1972 = dubitskii. nom. n.:
      bicorne Dumbleton, 1973 = crosbyi, nom. n.; borealis Malloch, 1919 =
      arctocanadensis, nom. n.; chelevini Ivashchenko, 1978 = ivashchenkoi, nom. n.;
      decafile Rubzov, 1976 = decafiliatum, nom. n.; frontatus Yankovsky, 1982 =
      boreopacificus, nom. n.; fulvipes Ono, 1978 = onoi, nom. n.; fuscum Rubzov, 1963
      = fuscatum, nom. n.; hibernale Rubsov, 1967 = lugense, nom. n.; intermedia
      Rubzov, 1956 = orenburgica, nom. n.; jacuticum, Rubzov, 1973 = tiksiense, nom.
      n.; kamtshaticum Rubzov, 1940 = kamtshadalicum, nom. n.; latitarsus Rubzov, 1971
      = mongolense, nom. n.; minutum Rubzov, 1959 = minuticorpus, nom. n.; rheophilum
      Tan et Chow, 1976 = tanetchowi, nom. n.; sedecimfistulata Rubzov, 1976 =
      dzhungarica, nom. n.; septentrionale Tan et Chow, 1976 = chowettani, nom. n.;
      tenuitarsus Rubzov, 1969 = chovdica, nom. n.).

PMID- 8984434
TI  - [The etiology and diagnosis of "black spot disease" of fish].
AB  - Some traditional points of view on the black spot disease in fishes caused by the
      metacercariae of the trematode Posthodiplostomum cuticola are revised. The black
      spot disease should be considered as one of several symptoms appeared in
      freshwater and sea fishes in cases of infection with certain parasite species. Up
      to present days, more than 30 parasite species causing similar symptoms are
      recognized. And among them 8 such species have been recorded in fishes of the
      Volga-Caspian region.

PMID- 8984435
TI  - [Parandrya feodorovi gen. n., sp. n.--a new cestode (Cyclophyllidea:
      Anoplocephalidae) from voles in Siberia].
AB  - A new genus and species of the anoplocephalid cestodes, Parandrya feodorovi gen.
      et sp. n. are described from the Western and Eastern Siberia voles. The new genus
      Parandrya is distinguished from the genus Andrya Railliet, 1893 by the presence
      of the cellular form of the uterus. The new genus also differs from other known
      genera of anoplocephalid cestodes associated with Rodentia, which have a single
      genital apparatus and cellular uterus, by the transformation of the external
      receptaculum seminis into the prostatio gland.

PMID- 8984436
TI  - [The detection of pathogenicity factors in the nematode Trichinella spiralis at
      different stages of its development].
AB  - The study of water soluble proteins of Trichinella spiralis has discovered for
      the first time some protein fractions having neiraminedase, haemagglutinative and
      cytotoxic activities. The presence of hyaluronidase was confirmed and its
      activity both for water soluble and cuticle proteins of the trichinella was
      examined. The haemagglutinin and cytotoxin of the trichinella have an antigen
      specificity. The presence of active molecules is considered as the factors of
      pathogenicity. These pathogenic factors were discovered in the invading larvae
      and adult Trichinella, while they were not found in young larvae.

PMID- 8984437
TI  - [The host-opportunistic protozoa system. The effect of ionizing radiation on the
      prevalence of cryptosporidiosis and pneumocystosis].
AB  - The aim of this study was to determine an influence of ionized radiation on the
      prevalence of Cryptosporidium and Pneumocystis carinii (P. c.) infections in
      children inhabitants of settlements affected by radionuclides after Chernobyl
      accident. Survey of children from day-care centers for prevalence of
      Cryptosporidium was carried out in Bryansk region, Russia, and Gomel and Mogilev
      regions, Belarus; children from cities Mogilev and Gomel as well as small town
      Pochep, Bryansk region, serve as control clean zones. Survey for P. c.
      seroprevalence was carried out in town Novozybkov, Bryansk region, Specific Ab to
      P. c. determined by "Pneumo-test" system (Nyarmedic. Moscow. Russia), an
      evaluation of immune status included assessment of Ig in serum and saliva by
      Manchini method. Results of the study were as follows: 1) of 432 healthy children
      surveyed for Cryptosporidium oocysts 352 were from affected regions: the
      prevalence in Bryansk region was 8% vs. 2.8% in control, in Gomel and Mogilev
      4.1% vs. 2.8%. 2) Prevalence anti-P.c. Ab accounts 56.3% in children and 78.2% in
      adult inhabitants of Novozybkov vs. 30% in children of control group. Special
      interest presents an relationship of seroprevalence P.c. and secretory immunity
      examined twice with 2 month interval. At the first survey IgG in seropositive for
      P. c. children was found in 36.8% (vs. 23.1% in control) and secretary IgA in
      13.2% vs. 5.8% in control. At the second survey IgG was found in 53.4% vs. 21.8%
      and IgA in 2.7% vs. 1.8% in control. Taking into consideration the known fact
      that IgG and IgA in saliva are result of their transudation from blood through
      the inflammatory mucosa we consider that long ionized radiation impairs the
      barrier function of mucosae.

PMID- 8984438
TI  - [Changes in the number of deer louse-flies Lipoptena cervi (Hippoboscidae) in the
      forests of northwestern Russia].
AB  - Long term observations of the abundance fluctuations of the deer louse-fly
      Lipoptena cervi were carried out in forest areas of the Leningrad, Novgorod and
      Pskov provinces in 1988-1995. The registration of the winged individuals was held
      in the period of the mass flight in August by the number of deer louse-flies
      attacking a collector man during 1 km of the pathway. The abundance of deer louse
      flies was being high everywhere up to 1993, while it decreased by 8-29 times in
      1994-1995. The reason of the abundance decrease of deer louse-flies is the abrupt
      abundance decrease of the main host, the elk Alces alces.

PMID- 8984439
TI  - [Borreliosis in laboratory rabbits].
AB  - The borreliosis of laboratorian rabbits displays as a chronic infection with
      recurrences during a spring-autumn season. The clinical picture includes a skin
      ulcerous lesion, arthritis accompanied by lymphocytosis and borreliemia.

PMID- 8984440
TI  - [The fleas of mammals from the Ucayali River basin (the Peruvian Amazonia)].
AB  - The material collected from 57 specimens of 9 mammalian species in two localities
      of the Peruvian Amazonia includes 212 specimens of fleas belonging to four
      species (Polygenis klagesi, Ropalopsyllus lugubris, Rh. australis and
      Rothschildopsylla noctilionis). This is the first record of fleas in the Ucayali
      River basin. The majority of flea specimens were collected form three
      morphologically similar but karyotypically and electrophoretically distinct
      species of spiny rats of the genus Proechimys. These fleas belong to the species
      P. klagesi. The subspecies P. k. samuelis was collected from 32-chromosome spiny
      rats nearby Pucallpa (8 degrees 22' S, 74 degrees 43' W), whereas in the locality
      nearby the village Jenaro Errera (4 degrees 52' S, 73 degrees 39' W) only the
      nominative subspecies P. k. klagesi were collected from all three species of
      spiny rats. Other species of fleas have relatively less abundance. Six fleas Rh.
      l. lugubris were found on one specimen of Cuniculus paca; a single Rh. australis-
      on one specimen of Myoprocta pratti; and a single R. noctilionis--on one specimen
      of Eptesicus brasiliensis.

PMID- 8984442
TI  - [Geographic variability in the sexually mature phase of Ixodes persulcatus
      (Ixodidae). Experience in using databases on morphometry].
AB  - The aim of the article is to estimate geographic variation of Ixodes persulcatus
      adults as a whole. Intraspecific variation of the females and males of Ixodes
      persulcatus Schulze, 1930 has been studied in eight geographical localities
      ("populations") of its distribution range (fig. 1.). The distance between western
      and eastern localities is more than 8700 km, between northern and southern ones
      it is approximately 2900 km. Twenty five to thirty specimens of each sex were
      studied in each geographical locality. The following eleven characters were used
      (fig. 2, 3): length of scutum (conscutum), width of scutum (conscutum), length of
      anal ring, width of anal ring, length of spiracular plate, width of spiracular
      plate, length of gnathosoma, width of gnathosoma, length of II-III articles of
      palps, length of hypostome, length of tarsus 1. The multidimensional scaling
      method by means of software package SYSTAT was used for estimation of
      relationships between populations on the basis of morphometrical data. The
      differences between the populations were revealed only from absolute sizes of
      organs, whereas their proportions (i. e. shape) were constant in all geographical
      localities. Fig. 4, 1 shows that females from localities G (Primorski Territory)
      and C (Tien Shan Mountains) occupy extreme positions. Fig. 4, 2 shows that males
      from localities G (Primorski Territory) and D (SW Altai Mountains) on the one
      hand and A, B (European) on the other one occupy extreme positions. Locality C
      (Tien Shan Mountains) is similar to F (Western Sayan Mountains) and to European
      (A, B) whereas females of locality C differ from A, B and F. Taking into account
      the partial discrepancy of relationships between populations in sexes we have
      united the data on corresponding characters of both sexes in the aggregate data
      base (fig. 4, 3). This was possible owing to the multidimensional scaling method.
      Fig. 4, 3 shows isolated position of the population G (Primorski Territory),
      specimens of which are the largest in sizes. The populations D (SW Altai
      Mountains) and H (Sakhalin Island) are morphometrically most similar to the
      population G. The population C (Tien-Shan Mountains) is represented of the
      smallest specimens. The European populations (A and B) are closer to C. The
      largest sizes are typical of the populations G and D associated with relict
      Tertiary landscapes of Primorski Territory and SW Altai with which areas of
      ecological optimum of I. persulcatus coincide. The smallest sizes are observed in
      the European populations (A, B) near the north-western boundary of the
      distribution range of the species, as well as in the Alpine population of Tien
      Shan Mountains, near the upper vertical boundary of the distribution range (2000
      3000 m above sea level). Climatic conditions of the habitat in these areas are
      similar to those of the northwestern part of the distribution range of I.
      persulcatus.

PMID- 8984441
TI  - [The place of ixodid ticks (Ixodidae) in forest ecosystems].
AB  - The ticks Ixodes ricinus and I. persulcatus are the dominant tick species in the
      forest ecosystems of the temporary zone of Eurasia. They occur within their
      areals in every types of forests except arid and marsh biotopes. The density of
      tick populations per square unit exceed many times those of dominant species of
      mammals and birds living in the same ecosystems. In optimal conditions the
      abundance of hungry larvae per 1 square km varies from hundreds of thousands to
      several millions, that of nymphs-from thousands to several hundreds of thousands,
      and that of imago counts several thousands. The number of larvae and nymphs
      simultaneously feeding on rodents or shrews usually not exceeds several
      specimens. However, in case of 50-100% infection rate of hosts and long seasonal
      period of parasitizing the greater part of individuals in the main host
      population is repeatedly attacked by ticks and therefore supports a significant
      number of parasites. Despite of annual fluctuations of ticks and hosts abundance
      the parasitic systems formed by them are characterized by high stability in time
      and space. The high resistance of the tick parasitic systems to the influence of
      unfavorable factors is caused by several independent and duplicated systems of
      tick's interaction with their hosts and environment. The ticks and their hosts
      together with agents of the tick borne encephalitis, Lime disease, babesiosis and
      other transmissive infections form the three component parasitic systems of
      higher rank. These systems are referred to as the natural foci of diseases and
      their geographical distribution in general lines coincide with species areals of
      I. ricinus and I. persulcatus.

PMID- 8984443
TI  - [The host-opportunistic protozoa system. The incidence of mixed infections
      (Pneumocystis and cytomegalovirus) in children living in radionuclide
      contaminated areas].
AB  - The purpose of our study was to determine the influence of ionized radiation onto
      the frequency of mixed infections (P. carinii and Cytomegalovirus) in children
      inhabitants of the settlements affected with radionuclide after Chernobyl
      accident. Two groups of children were under survey. 1) 103 inhabitants of
      Novozybkov (Bryansk Province, Russia) and 38 patients under observation in Moscow
      paediatric hospital from another affected villages (5-15 Ci/km2) were examined
      serologically by the diagnostic system "Pneumo-test" and "Cytomegatest"
      (Nyarmedic, Moscow, Russia). Cut-off titers for P. carinii were IgM-1: 200, IgG
      1: 20, for CMV IgG-1: 200, 2) Retrospective study of 563 patients with
      respiratory pathology and 1809 died children after acute pneumonia during 14
      years period. Sputum and mucus of the patients taken by laryngoscopy and
      bronchoscopy were studied for P. carinii by microscopy, the section of lungs-
      histologically. The sediments of urine and saliva were examined for CMV by
      microscopy and section of different organs_-histologically. Examinations were
      performed by one and the same highly qualified pathologist. The results of the
      study were as follows. 1. Of 563 children examined for both P. carinii and CMV
      186 (33%) were positive for P. carinii and 189 (33.7%) for CMV. Both pathogens
      were found in 46 children (8.2%), mainly among 1-2 and 6-12 month age (8.5 and
      14.5%, respectively). Retrospective analysis of 1809 autopsy results shows, that
      in 73 cases (4%) were found only P. carinii, in 200 (11.1%) only CMV and in 24
      (1.3%) two pathogens simultaneously. 2. Of 103 children surveyed serologically P.
      carinii monoinfection was found in 7 (8.8%), CMV-in 25 (24.3%) and coinfection in
      55 (53.4%). Estimated frequency for coinfection (if combination of two infections
      were to be accidental) should equal 46.8%. In control group consisted of 30
      children from clean Moscow region the rate of coinfection was 16.7% and estimated
      rate 15% (the difference between empiric and estimated rates are statistically
      significant, t > 4). Thus it is clear that the rate of coinfection of P. carinii
      and CMV is always high either in clean or in affected by ionized radiation
      regions. This rate determined by microscopy was higher in patients (8.2%) than in
      autopsy cases (1.3%) and much higher in children from affected region (53.3%)
      than in control (16.7%), being determined serologically. Separate interest
      present geometric mean titers found in the cases of coinfection. The titer for
      anti-CMV IgG in children from affected regions was rather high (5884 vs. 1246 in
      control) and on the contrary titers for anti-P. carinii IgM and IgG were lower
      than in control (512 vs. 1245 and 58 vs. 159 respectively). We are incline to
      interpret the results of our study as evidence of increased susceptibility to P.
      carinii and CMV in those children whose immune system was suppressed by premorbid
      factors or ionized radiation and peculiar symbiotic relationships of P. carinii
      and CMV resulting in enhancement of their infectiousness.

PMID- 8984444
TI  - [The taxonomic independence of Anoplocephaloides spp. (Cestoda: Anoplocephalidae)
      with serial alternation of the genital atria].
AB  - The mutual dispositions of the genital apertures in the anoplocephalidean
      strobila and their taxonomical significance were considered. The irregular
      alternations of single genital apertures from the alternations of its seria on
      the proglottid margins could be distinguished. The serial alternation as an
      intermediate type in the transformation from the irregular to unilateral
      dispositions of the genital apertures were considered. The conclusion about the
      Anoplocephaloides spp. with the serial alternations of genital apertures as a
      separate taxon was presented. The validity of the genus Gallegoides was
      renewaled. New genus Paranoplocephaloides gen. n. and a new species P.
      schachmatovae sp. n. from the voles Microtus oeconomus were described. Diagnoses
      on these taxa were given. A new combination Paranoplocephaloides rauschi comb. n.
      was designed.

PMID- 8984445
TI  - [The species composition of fleas (Siphonaptera) from northwestern Russia].
AB  - The check-list of fleas of the northwest of Russia, includes 56 species. Among
      them, 40 species have been actually recorded in the region in question, while the
      occurrence of rest 16 species is suggested according to their distribution in
      adjacent areas. The fleas of the northwest Russia belong to 7 families. All flea
      species of the region in question including recorded and suggested species are
      distributed among these families as follows: Pulicidae--5 species, Vermipsillidae
      -3, Ceratophyllidae--23, Leptopsyllidae--5, Ctenophthalmidae--11,
      Hystrichopsillidae--1, Ischnopsillidae--8.

PMID- 8984446
TI  - [Morphological criteria of the species in cercaria of the genus Diplostomum
      (Trematoda: Diplostomidae) and methods for their study].
AB  - Taxonomy values of morphological features used for differential diagnostics of
      different taxa is considered for cercariae of the genus Diplostomum. It was shown
      that, as a rule, taxa criteria of superspecies ranks had a qualitative nature and
      were easily detected in live cercaria studies. In contrast, cercariae species
      diagnostics (CSD) is based exclusively on less significant, from a taxonomy point
      of view, quantitative features presenting absolute and relative body dimensions
      and that of cercariae organs as well as peculiarities of their cuticular
      armament. All this compels a taxonomist to use for CSD a whole range of
      diagnostic features of groups mentioned and increase their taxonomy values owing
      to standardization of cercariae collection, fixation and subsequent processing
      techniques, as well as broader application of variation-statistic methods of
      analysis that is possible only in cercariae studies through a use of permanent
      slices. A complex of methodical devices, which observance will ensure reliable
      CSD of the genus mentioned, is proposed. It encompasses cercariae collection and
      fixation as well as mounting of permanent balsame slides with preceding cercariae
      treatment with acetic-acid carmine (morphometric analysis), acid fuxine Sekki
      (cuticular armament staining) and silver nitrate (sensory apparatus detection).
      The reagents mentioned may form a real base for a creation of cercariae museum
      collections being not inferior in scientific value to existing trematode maritae
      and metacercariae stocks.

PMID- 8984447
TI  - [Shrews as a Borrelia reservoir in northwestern Russia].
AB  - The borreliemia was discovered in 22 (44.9%) of 49 common shrews (Sorex araneus,
      Soricidae), which were captured in the end of July-August 1995 in the Novgorod
      Province. The borreliae were located near the capillaries of the true skin and in
      the veins of the subcutaneous layer.

PMID- 8984448
TI  - [Modification of the liver phospholipid status of cattle by Orientobilharzia
      turkestanica trematodes].
AB  - The paper gives the data on a trematode influence onto the phospholipid (PL)
      contents in the liver of cows. It is shown, that the decrease of PL basic
      fraction concentrations, i.e. phosphatidilcholin (PC) by 20% and
      phosphotidilethanolamin (PE) by 26%, during the period of infection is
      accompanied by the increase of respective lysoforms, namely, lysoPC by 240%, and
      lysoPE by 160%, and as well as minor forms, PL-diphosphotidilgleserol by 70%,
      sphingomielin by 47% and phosphatidilserin by 41%. It is suggested, that the
      infection of cow liver by trematodes determines such contents and principles of
      membrane structures, which decrease their functional activity and probably
      increase its permeability for ions, some metabolites and low molecular
      carbohydrates.

PMID- 8984449
TI  - [A redescription of Hepatocestus hepaticus (Cestoda: Dilepididae) from shrews in
      western Siberia].
AB  - The redescription of the cestoda Hepatocestus hepaticus (Baer, 1932) was made on
      the original material from the Western Siberia shrews in connection with the
      first registration this species at shrews within the east palearctic. The
      analysis of the morphology of the H. hepaticus from the western Siberian
      populations of shrews hadn't reveal essential morphological distinctions as
      compared with their western palearctic populations except that we didn't found
      the uterine capsules in the specimens studied by us. Crocidura sibirica Dukelsky
      was been registered as the definite host of this cestoda at first.

PMID- 8984450
TI  - Hymenolepis diminuta: metacestode-induced reduction in the synthesis of the yolk
      protein, vitellogenin, in the fat body of Tenebrio molitor.
AB  - Vitellogenin synthesis by the fat body has been monitored using in vitro culture
      and immunoprecipitation. This system was found to be efficient for measuring
      vitellogenin production in both non-infected Tenebrio molitor and those infected
      with Hymenolepis diminuta. In fat bodies from infected beetles, vitellogenin
      production was decreased by up to 75% (day 24 post-infection) and, at all times
      investigated, vitellogenin synthesis was significantly below control levels (days
      3-30 post-infection). Incubating fat bodies from control insects with isolated
      metacestodes indicated that this may be a direct effect by the parasite which is
      developmental stage-specific. Stage II, but not Stage III-IV, not heat-killed
      parasites could bring about this decrease in vitellogenin. In addition, these
      effects may be density dependent within the range of 2-20 parasites per fat body;
      only 2 metacestodes were necessary to cause a significant decrease. Since
      metacestodes do not take up vitellogenin, nor limit the amount of [14C]leucine
      available to the fat body for vitellogenin production, it is conceivable that the
      parasite produces a potent inhibitor of vitellogenin synthesis, or a molecule
      which induces cells within the fat body.

PMID- 8984451
TI  - Blunt abdominal trauma.

PMID- 8984452
TI  - Ductus arteriosus aneurysm.

PMID- 8984453
TI  - Caffey's disease.

PMID- 8984454
TI  - Pulmonary artery sling shown on MRI.

PMID- 8984455
TI  - MRI of dysplasia epiphysealis hemimelica.

PMID- 8984456
TI  - The "sticky suture"--a roentgen-sign of postural flattening.

PMID- 8984457
TI  - Oncology Nursing Society 21st annual congress. Philadelphia, Pennsylvania, May 2
      5, 1996. Abstracts.

PMID- 8984458
TI  - Quality of lives.

PMID- 8984459
TI  - Stress in a GP partner.

PMID- 8984460
TI  - One-stop breast clinics.

PMID- 8984461
TI  - Easier access to MRI scanning?

PMID- 8984462
TI  - Cox 2: the next stage in the NSAID story.

PMID- 8984463
TI  - Defibs: a GP guide to ICDs.

PMID- 8984464
TI  - Oral contraceptives and the risk of DVT.

PMID- 8984465
TI  - Shingles.

PMID- 8984466
TI  - Preparing for the MRCGP.

PMID- 8984467
TI  - Evidence, art or anecdote?

PMID- 8984468
TI  - [Questionnaire on psychosexual development of children--development of a
      guideline for diagnosis of sexual abuse].
AB  - The purpose of this paper is to present a questionnaire which can collate data on
      the psychosexual development of children. There are as yet few contributions from
      the field of empirical research dealing with the question of "normal"
      psychosexual development patterns. There is also a lack of standardised
      procedures by which this aspect of child development can be assessed. For this
      reason we have developed a questionnaire relating to the theme of child sexuality
      which can be used in the framework of history and which was examined as part of a
      clinical study supported by a grant from the Deutsche Forschungsgemeinschaft. The
      questionnaire contents questions put to parents relating to the sexual
      development of children, on how sexuality is talked about and dealt with in the
      family, and on precisely-defined and described experiences of the child and other
      members of the family. At the time we present a method of judging normative
      sexual development of the child and of disturbances such a sexual abuse. In order
      to deal with this question the collation of information from four different areas
      is required: physical development and symptoms, behaviour of the child, family
      context including psychosocial adversities and parent-child interaction. Case
      studies will illustrate how data from the four areas are related and can
      accordingly be assessed in order to be able to make judgments on the psychosexual
      development of children. We see this method as helpful in order to determine
      whether or not a child was sexual abused. Thus, consideration of each individual
      case in context is necessary if a balanced judgment is to be arrived at.

PMID- 8984469
TI  - [Evaluation of preventive group intervention for children of divorce].
AB  - Following the results of American intervention programs for children of divorce,
      the effects of a preventive group program for 10 to 12 year old children of
      divorced families were studied within a pretest-posttest design. The aim of the
      intervention was to decrease children's fears, increase their feelings of self
      esteem and to improve the relationship to their parents. The program consists of
      10 group-sessions about divorce related changes and experiences in the children
      families and 3 evenings for their parents. Subjects were 5 boys and 2 girls. The
      results show that after the intervention fears are decreased, feelings of self
      esteem are increased and the subjective perception of the own family is more
      positive than before. The results are discussed in terms of the further
      development of interventions for children of divorce.

PMID- 8984470
TI  - [The Linz model: separation--divorce--new beginning].
AB  - The Linz-Project is a secondary-preventive and therapeutic model for coping with
      divorce. It contains a children's group (for children with age 8-12) and
      parallelly a parent group. The authors describe context, theoretical and
      practical fundamentals, aims, methods, basic structure and process of this
      specific group model. Their article outlines similarities and differences to
      other group models for coping with divorce and resumes the experiences with the
      Linz-Project.

PMID- 8984472
TI  - [Comparative assessment of carboxymethylcellulose sorption properties with
      respect to hemin and globin].
AB  - Adsorption of hemin and globin onto fibrous carboxymethylcellulose (CMC) that is
      commonly used in food industry was studied. The process of CMC saturation with
      hemin (and globin) was shown to depend on time and temperature. Constants for
      adsorption and the activation energy for the adsorption of globin were
      determined. A Langmuir-type hyperbolic adsorption was observed for globin,
      whereas the hemin adsorption on CMC was linear. Optimum conditions for globin
      isolation from hemoglobin solutions were found.

PMID- 8984471
TI  - [Use of aerosol OT reverse micelles in heptane for purifying superoxide dismutase
      from erythrocytes].
AB  - Reversed micelles of Aerosol-OT (AOT) in heptane were used to purify superoxide
      dismutase (SOD) from bovine red blood cells. Effects of pH, temperature,
      concentrations of NaCl and protein in the aqueous phase, and the AOT to protein
      ratio on the extraction of the concomitant proteins from the aqueous into
      micellar phase were studied. The conditions were found that provided the
      extraction of concomitant proteins into micelles of AOT in heptane and left SOD
      in the aqueous phase. The SOD was electrophoretically pure; therefore, the need
      for its purification using chromatography was excluded.

PMID- 8984473
TI  - [Modification of Bacillus intermedius ribonuclease by dialdehyde dextran].
AB  - Conditions for modification of Bacillus intermedius ribonuclease with dialdehyde
      dextran was optimized by Box and Wilson's method to achieve the enzyme with
      higher activity. The generalized parameter including the yield of enzyme protein
      and enzyme stability during modification was used. The yield of activity and
      preparation characteristics depended on a number of enzyme-carrier bonds.

PMID- 8984475
TI  - [Problems in creating insulin preparations with increased stability against
      proteolysis].
AB  - Chemical methods that accelerate the transport of insulin and other polypeptides
      across biological membranes and increase their resistance to enzymatic hydrolysis
      are reviewed. These methods include chemical modification of insulin
      macromolecules, the use of compounds that increase the permeability of biological
      membranes or inhibit enzymatic proteolysis, the hormone immobilization in a
      polymer coat protecting it against the aggressive environment, the incorporation
      of insulin into liposomes, etc. The advantages and drawbacks of these methods are
      analyzed, and promising lines of research in this field of applied biochemistry
      are described.

PMID- 8984474
TI  - [Cloning the Saccharomycopsis fibuligera alpha-amylase gene and its expression in
      Saccharomyces cerevisiae].
AB  - The alpha-amylase gene of yeast Saccharomycopsis fibuligera was cloned, partially
      sequenced, and expressed in Saccharomyces cerevisiae. Four amino acid
      substitutions were identified in the enzyme structure as compared to the earlier
      cloned gene. The Saccharomycopsis fibuligera alpha-amylase gene was expressed in
      Saccharomyces cerevisiae under the control of its own promoter. The native alpha
      amylase signal peptide provided an efficient secretion of the enzyme by
      Saccharomyces cerevisiae. The efficiency of the alpha-amylase secretion was 98%.
      The pH optimum of the enzyme secreted by Saccharomyces cerevisiae was 4.0.

PMID- 8984476
TI  - [Purification of acetylcholinesterase from human erythrocytes using metal-chelate
      affinity chromatography].
AB  - Acetylcholinesterase (AChE) was purified on columns with iminodiacetate Agarose
      charged with Cu2+, Zn2+, and Ni2+. The best results (a 14-fold purification and
      more than 30% activity yield) were obtained with Zn2+ used as a complex-forming
      metal. The preparation had a specific activity of approximately 7 U. Its purity
      was tested by polyacrylamide gel electrophoresis under denaturing conditions.

PMID- 8984477
TI  - [Use of microscopy and inoculation for bacteriologic diagnosis in tuberculosis
      patients by the materials of Ivanovo region].
AB  - The paper describes guidelines for isolation of Mycobacterium tuberculosis by
      bacterioscopy. It shows high detection rates for Mycobacteria in patients
      included into the programme. The detection rates of patients by bacterioscopy are
      not different in two quarters.

PMID- 8984478
TI  - [Chemotherapy effectiveness of tuberculosis patients in intensive phase (2-3
      months)].

PMID- 8984479
TI  - [State and prospects of antituberculous care for the population of the Republic
      of Marii El].
AB  - The paper briefly outlines the history of the Republican antituberculosis
      dispensary which is 70. It gives the present-day tuberculosis epidemiological
      parameters in the republic. It is pointed out that from 1991 to 1995 morbidity
      rates rose by 85% and made up 48.4 per 100,000. Morbidity rates in the republic
      are affected by the population's lower living conditions, decreased scope of
      medical aid due to inadequate financial funds and uncompleted staff. Transition
      to more short-term courses of chemotherapy by the WHO scheme and reduction of
      follow-up duration in the groups registered in dispensaries.

PMID- 8984480
TI  - [Experience with classical methods for serodiagnosis of tuberculosis in detecting
      drug resistance of mycobacterium].

PMID- 8984481
TI  - [Detection of patients with tuberculosis and current methods of chemotherapy].

PMID- 8984482
TI  - [Diagnosis and treatment of acute progressive tuberculosis types].
AB  - An examination was made of 77 patients with extensive segmentary and lobular
      pulmonary tuberculous lesions: caseous pneumonia (n = 26), infiltrative caseous
      pneumonia (n = 18), fibrocavernous pneumonia complicated by caseous pneumonia (n
      = 16), and disseminated tuberculosis (n = 17). All patients had destructive
      changes; in 82.7% of patients the caverns were large and great in size. Bacteria
      were isolated in 94.8%, mycobacterial drug resistance was noted in 51.8%. Four
      variants of the course of a disease were identified: 1) that with predominance of
      the intoxication syndrome (41.6%); 2) that with respiratory failure (24.7%); 3)
      that with pulmonary hemorrhage (15.6%), 4) that added by secondary microorganisms
      (18.2%). Chemotherapy included a combination of 4 or 5 drugs along with
      pathogenetic tools, which stabilized a process in 80% of patients and arrested
      bacterial isolation in 69.5%. In 20%, the process continued to progress and in 3
      of them died.

PMID- 8984483
TI  - [Exacerbation of pulmonary tuberculosis during chemotherapy].
AB  - Progression of a tuberculosis process during antituberculous therapy is most
      commonly evoked by its inadequacy. The latter may be associated with undiagnosed
      drug resistance, patients' incompliance due to the lack of their consciousness or
      discipline. In these circumstances, the use of stimulating pathogenetic
      treatments can provoke an exacerbation. Decreased immune defense mechanisms after
      experienced intercurrent infections may also serve as one of the common causes of
      tuberculosis exacerbations. Only in rare cases, progression of clinical and X-ray
      symptoms is explained by the massive pathogen lysis syndrome (Jarisch
      Herxheimer's syndrome) The management policy for these patients should be
      different due to the causes of exacerbations.

PMID- 8984484
TI  - [Comparative analysis of the results of spinal fluid microbiological study in
      children and adults who suffered from tuberculous meningitis].
AB  - An examination was made of 133 children and 89 adults, aged 3 to 60 years, who
      had admitted for suspected tuberculous meningitis. The diagnosis of tuberculous
      meningitis was established in 113 children and 79 adults. In the remaining 20 ill
      children and 10 adult patients, tuberculous etiology of the disease was rejected.
      After puncture, spinal fluid was examined by three methods, bacretioscopy,
      cultivation, and biological assay. Bacterioscopy detected Mycobacteria
      tuberculosis in 5.3 and 2.5% of ill children and adults, respectively. Types of
      M. tuberculosis were isolated more frequently in children (n = 66 (58.4%)) than
      in adults (n = 22 (27.9%)) by bacteriology and in 39 (34.5%) and 15 (30.0%)
      adults by biological assay. The spinal fluid much more frequently displayed
      changed forms (L forms) of M. tuberculosis than bacterial ones. They were
      isolated in 62 (54.9%) and 59 (74.6%) adults by cultivation. On the whole, spinal
      fluid cultivation for L forms of M. tuberculosis allowed the total detection
      percentages for an etiological factor to be increased in children and adults, who
      both suffered from tuberculous meningitis, they accounted for 87.6 and 87.3%,
      respectively.

PMID- 8984485
TI  - [Secondary immunodeficiency of medical staff contacting with tuberculous and
      nonspecific infection].
AB  - The present paper analyzes immunological parameters and the incidence of
      secondary immunodeficiency (SID) in physicians and medium-levelled medical staff
      contacting with tuberculous and non-specific infection. Suppressed cell immunity
      was recorded in 44% of the medical staff of a pulmonary surgical tuberculosis
      hospital, with increased length of service there was a rise in the number of
      patients diagnosed as having immunodepression. The clinical manifestations of SID
      were recorded in 56% in this group and they were most pronounced in a group of
      long-working personnel. The proportion of persons with immunodepression proved to
      be twice higher among nurses than among physicians. Nurses are at the highest
      risk for immunopathological states. This common occurrence of SID among medical
      staff is an indicator to make an obligatory regular immunological examinations of
      the staff for the prevention and immunotherapy of SID.

PMID- 8984486
TI  - [Body's responsiveness and postoperative course in patients with pulmonary
      tuberculosis].
AB  - The purpose of the study was to reveal a package of criteria for the body's
      responsiveness in order to predict the course of a postoperative period in 25
      patients with short-term pulmonary tuberculosis. The indices of the
      responsiveness were comparable with the specific features of a postoperative
      course. The study of the body's responsiveness prior to surgery and in the first
      days after it was found to be of value in the prediction of a postoperative
      course. The determination of the intensity of free radical processes may more
      accurately estimate the impact of surgical interventions on the body's
      responsiveness. The drastic rise in the activation of free radical oxidation
      after surgery suggests its unfavourable influence on immune mechanisms.

PMID- 8984487
TI  - [Potentialities of methods for digital processing of lung x-ray films].

PMID- 8984488
TI  - [Experience in treating uveitis of sarcoid etiology].

PMID- 8984489
TI  - [Production of tumor necrosis factor-alpha and interleukin-1 beta in patients
      with pulmonary tuberculosis in relation to the course of a process and
      immunological features].
AB  - The production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta
      (IL-1 beta) by peripheral mononuclears induced by prodigiosane, tuberculin,
      phytohemagglutinin and unduced and the serum levels of the above cytokines were
      studied. There was an relationship between the production of TNF-alpha in the
      patients' peripheral blood and the type and pattern of a tuberculosis process.
      The similar tendencies were found in the production of IL-1 beta. It was found
      that the production of IL-1 beta was higher in patients with a more predominant
      humoral immune response and that of TNF-alpha was greater in those with a more
      cellular response. There were the most marked relationships of cytokine synthesis
      to the degree of clinical parameters in prodigiosan cell induction of cells and
      to immunological parameters in tuberculin-induced cell stimulation.

PMID- 8984490
TI  - [Natural killer cells and adenosine deaminase activity in patients with pulmonary
      tuberculosis].
AB  - Natural killer cells (NKC) were studied in 150 patients with first revealed
      destructive pulmonary tuberculosis, 100 with fibrocavernous and 50 with cirrhotic
      pulmonary tuberculosis by assessing their peripheral blood levels, cytotoxic
      activity and specific activity of adenosine deaminase. The latter 2 parameters
      were determined in bronchoalveolar lavage fluid. Different types of pulmonary
      tuberculosis were demonstrated to be accompanied by varying NKC depressions.

PMID- 8984491
TI  - [Recovery of immunological responsiveness in patients with bronchial asthma
      during nicotinamide treatment].
AB  - It has been found that among patients with bronchial asthma (BA) there are
      individuals with primary complete or partial lymphocytic resistance to
      glucocorticoid hormones (GC), which is apparently to be associated with cellular
      immunodeficiency and lower counts of young cortisol-sensitive cells in these
      patients. This condition may be aggravated with GC use and may appear as steroid
      dependence with all its clinical manifestations. It has been demonstrated that
      cellular steroid dependence may be either decreased or completely eliminated by
      special therapy aimed at enhancing lymphocytic sensitivity to hormones.
      Nicotinamide served as the drug of choice, which promoted the recovery of GC
      lymphocytic sensitivity, which may be attributed to the positive effects of the
      drug on the systemic immunity of BA patients.

PMID- 8984492
TI  - [Pulmonary surfactant].

PMID- 8984493
TI  - [Chronic cor pulmonale (lecture)].

PMID- 8984494
TI  - [Primary iliac tuberculosis in an adult].

PMID- 8984496
TI  - [Bettolepsia++ ++ in a patient with pulmonary tuberculosis].

PMID- 8984495
TI  - [International concept of antituberculous care organization for the Tomsk
      region's population].
AB  - The priorities of the international concept of organization of antituberculous
      care to the population of the Tomsk Region are as follows: detection of bacillar
      patients and their short-term intensive chemotherapy by the WHO categories;
      formation of a 6-month reserve of tuberculostatics and complete control over
      patients' drug use; diagnosis of diseases by the general medical network for
      patients' referrals by introducing indications for clinical examinations for
      tuberculosis and sputum tests for Mycobacterium tuberculosis, fluorographic
      studies of only risk group populations; tuberculin diagnosis among children aged
      1-14 years from risk groups; BCG vaccination of the newborn and revaccination at
      the age of 6-7 years. Resource mobilization is essential. This includes:
      strengthening of basic service institutions and centralization of its structures;
      fund saving by reasonably reducing the beds in sanatoria and hospitals; extension
      of therapeutical and diagnostic services at the outpatient stage of a follow-up;
      decrease in the length of patients' medical examinations and in the number of
      groups registered at a tuberculous dispensary; intensification the work of a
      phtx11p4trist and a nurse with their salary increases.

PMID- 8984497
TI  - [Prospects for determining the activity of adenosine deaminase in biological
      fluids in tuberculosis].

PMID- 8984498
TI  - [Analytical survey of dissertation studies in specialty 14.00.26 "Phthisiatry "
      approved by the Higher Certifying Committee of Russia in 1995].

PMID- 8984499
TI  - [Analytical survey of dissertation studies in specialty 14.00.43 "Pulmonology"
      approved by the Higher Certifying Committee of Russia in 1995].

PMID- 8984500
TI  - [Tuberculosis control among children and adolescents: present-day status].
AB  - In recent years, there has been a rise in tuberculosis morbidity among children
      and adolescents in Russia. Society's social problems which contribute to the
      accumulation of an uncontrolled infection reservoir that is unknown to the
      antituberculous service system. The reservoir is formed primarily among children
      and adolescents who are brought up in socially disadapted, migrants' refugees, or
      homeless families, among delinquent children and adolescents. The existing
      complex of antituberculosis measures is under way only among permanent residents.
      In this connection, antituberculous measures in the above risk groups are to be
      improved. Some specific proposals are given in the paper.

PMID- 8984501
TI  - Large-scale purification and preliminary x-ray diffraction studies of human
      aspartylglucosaminidase.
AB  - Aspartylglucosaminidase (AGA) is a lysosomal asparaginase that takes part in the
      ordered degradation of glycoproteins and a deficiency of which results in a
      lysosomal accumulation disease aspartylglucosaminuria in human. The mature enzyme
      consists of 24-kDa and 17-kDa subunits, which are both heterogeneously
      glycosylated. Activation of the enzyme from a single precursor polypeptide into
      two subunits is accomplished in the endoplasmic reticulum (ER). The relative lack
      of this proteolytic capacity in several tested high-producing expression systems
      has complicated the production of active recombinant enzyme in high quantities,
      which would be an alternative for purification of this molecule for
      crystallization. Consequently, the AGA enzyme has to be purified directly from
      cellular or tissue sources for crystallographic analysis. Here we describe a
      large-scale purification method to produce milligram amounts of homogeneous AGA
      from human leukocytes. The purified AGA enzyme represents a heterogeneous pool of
      molecules not only due to glycosylation, but also heterogeneity at the
      polypeptide level, as demonstrated here. We were able to isolate a homogeneous
      peptide pool that was successfully crystallized and preliminary X-ray data
      collected from the crystals. The crystals diffract well to 2.0 angstroms and are
      thus suitable for determination of the crystal structure of AGA.

PMID- 8984502
TI  - [How is atropine made in belladonna? New findings on the regulation of plant
      secondary metabolites].

PMID- 8984503
TI  - [New drugs in the last year. Part 2. Antipsychotics].

PMID- 8984504
TI  - [Tricyclic benzomorphan analogs: synthesis and pharmacologic studies].

PMID- 8984505
TI  - [HIV: easier transmission through oral contact?].

PMID- 8984506
TI  - Insights into opioid action in the intestinal tract.
AB  - Opioids have been used for centuries as antidiarrhoeal drugs. In recent years,
      their mechanism and sites of action in exerting their antidiarrhoeal effect have
      been studied intensely. Attempts have been made to propose their general mode of
      action. Whilst there are numerous similarities in their general effects on
      motility, fluid secretion, and neuroeffector transmission, the differences
      between species, in some cases, can be remarkable. We highlight and contrast the
      similarities and differences in the commonly examined species and compare them to
      humans. Insights into mechanisms of opioid antidiarrhoeal action now also provide
      some new perspectives of opioid action in the intestine.

PMID- 8984507
TI  - Insect neurotransmission: neurotransmitters and their receptors.
AB  - The roles of acetylcholine, dopamine, octopamine, tyramine, 5-hydroxytryptamine,
      histamine, glutamate, 4-aminobutanoic acid (gamma-aminobutyric acid) and a range
      of peptides as insect neurotransmitters are evaluated in terms of the criteria
      used to identify transmitters. Of the biogenic amines considered, there is good
      evidence that acetylcholine, dopamine, octopamine, 5-hydroxytryptamine, and
      histamine should be considered to be neurotransmitters, but the case for tyramine
      is less convincing at the moment. The evidence supporting neurotransmitter roles
      for glutamate and gamma-aminobutyric acid at specific insect synapses is
      overwhelming, but much work remains to be undertaken before the full significance
      of these molecules in the insect nervous system is appreciated. Attempts to
      characterise biogenic amine and amino acid receptors using pharmacological and
      molecular biological techniques have revealed considerable differences between
      mammalian and insect receptors. The number of insect neuropeptides isolated and
      identified has increased spectacularly in recent years, but genuine physiological
      or biochemical functions can be assigned to very few of these molecules. Of
      these, only proctolin fulfills the criteria expected of a neurotransmitter, and
      the recent discovery of proctolin receptor antagonists should enable the biology
      of this pentapeptide to be explored fully.

PMID- 8984508
TI  - Protection of the myocardium by ischaemic preconditioning: mechanisms and
      therapeutic implications.
AB  - Preconditioning of the heart with brief periods of ischaemia protects the
      myocardium for up to 90 min against a more sustained ischaemic injury. A "second
      window of protection" occurs 24 hr after preconditioning with ischaemia. The
      cardioprotective effects of ischaemic preconditioning involve the release of
      mediators (adenosine, bradykinin, catecholamines, prostaglandins, endothelin-1),
      which either alone or in concert activate protein kinase C, which translocates to
      the cell membrane. This manuscript reviews (i) the cardioprotective effects of
      ischaemic preconditioning, (ii) the underlying mechanisms, (iii) the effects of
      ischaemic preconditioning of other tissues (skeletal muscle, brain and kidney),
      and (iv) the clinical implications.

PMID- 8984509
TI  - Cytokines and their receptors in the central nervous system: physiology,
      pharmacology, and pathology.
AB  - Numerous cytokines and their receptors have been identified in the brain, where
      they act as mediators of host defence responses and have direct effects on
      neuronal and glial function. Experimental tools for studying cytokine actions,
      their source and control of synthesis in the brain, actions and mechanisms of
      action will be reviewed here. In particular, the cytokines interleukin-1,
      interleukin-6, and tumour necrosis factor-alpha have been implicated in the
      central control of responses to systemic disease and injury and activation of
      fever, neuroendocrine, immune, and behavioural responses. The recent discovery of
      specific inhibitors of cytokine synthesis, release, or action may offer
      significant therapeutic benefit.

PMID- 8984510
TI  - Induced differentiation, the cell cycle, and the treatment of cancer.
AB  - Hybrid polar compounds, of which hexamethylene bisacetamide (HMBA) is the
      prototype, have been shown to be potent inducers of differentiation of many types
      of transformed cells. With virus-transformed murine erythroleukemia cells as a
      model, HMBA was shown to cause these cells to arrest in G1 phase and express
      globin genes. HMBA action involves modulation of factors regulating G1 to S phase
      progression, including a decrease in the G1 cyclin-dependent kinase 4
      accumulation of underphosphorylated retinoblastoma protein, and an increase in
      the level of both retinoblastoma protein and the related protein, p107. In turn,
      p107 complexes with transcription factors such as E2F and, presumably, inhibits
      transcriptional activity of these factors for genes whose products are required
      for DNA synthesis. This provides a possible mechanism for HMBA-induced terminal
      cell division of transformed cells. Evidence that hybrid polar compounds have
      therapeutic potential for cancer treatment is also reviewed.

PMID- 8984511
TI  - Influence of conformational flexibility of their active sites on the electronic
      conductivity of enzymes.
AB  - The a.c. conductivity of the proteins lysozyme and subtilisin, both in their
      active and inactive or inhibited forms were determined theoretically. For this,
      quantum mechanical calculations and a random walk theory were used. The
      conclusions are that these enzymatic proteins can easily transport electrons
      which is most probably important in their role as catalysators of biochemical
      reactions. The electron transport is sensitive to three-dimensional changes of
      the active sites of these enzymes which have more flexibility than the whole
      molecule. Therefore, the flexibility of the active sites of enzyme catalysts is
      not only important for the conformational fitting with the reactants, but also
      strongly influences the transport in biochemical reactions.

PMID- 8984512
TI  - [The study of the relationship between cholesterol and lipid concentration and
      suicidal behavior in patients with schizophrenia affective illness].
AB  - In 143 patients (63 male, 80 female), admitted to the Department of Adult
      Psychiatry, University of Medical Sciences in Poznan, throughout the period from
      1 October 95-31 March 96, with the diagnosis of schizophrenia (46 patients),
      endogenous depression (79 patients) or mania (18 patients), serum concentration
      of total cholesterol, LDL and HDL cholesterol, triglycerides and total lipids was
      estimated during the first days of admission. The occurrence of suicidal
      behaviors (thoughts, tendencies or acts) in these patients during the period of 3
      months preceding the admission was also determined. The occurrence of suicidal
      behavior was found in 74 patients (30 male, 44 female). The persons revealing
      suicidal behaviors had significantly lower concentrations of total cholesterol,
      LDL cholesterol, triglycerides and total lipids compared with patients without
      such behaviors. This relationship was observed in all diagnostic groups as well
      as in both younger (below 32 years) and older (over 40 years) groups of patients.
      The results obtained confirm previous reports on the association between low
      cholesterol concentration and an increased risk of suicidal behavior in patients
      with psychiatric disorders. Authors discuss possible mechanisms and also clinical
      implications of this finding.

PMID- 8984513
TI  - [Biological mechanisms of drug-resistant depression].
AB  - The authors review recent findings concerning biological mechanisms of drug
      resistant depression. Treatment-resistant depression may result from the
      inability of antidepressants to normalize serotonergic transmission. Efficacy of
      therapeutic strategies enhancing serotonergic function such as potentiation of
      tricyclic antidepressants with lithium or fluoxetine as well as effectiveness of
      selective serotonin reuptake inhibitors in drug-resistant depression may support
      this hypothesis. Limbic-hypothalamic-pituitary-adrenal axis hyperactivity may be
      also an important factor of the persistence of depression, and so treatment with
      inhibitors of steroid biosynthesis may bring about readjustment of this axis and
      remission of depression in some cases of drug-resistant depression with
      hypercortisolemia. Another subtype of drug-resistant depression may be related to
      a dysfunction of hypothyroidism. Some evidence suggests also a relationship
      between drug resistance in depression and changes in the immune system. Research
      on biological mechanisms of drug-resistant depression may help clinicians to
      decide on the most appropriate treatment strategy in resistant depression as well
      as to shed light on the pathomechanism of depression.

PMID- 8984514
TI  - [Long-term administration of lithium carbonate: experience based on a case of 25
      year-long treatment with lithium].
AB  - In the beginning of 1960s, initial reports appeared pointing to a possibility of
      preventing depressive and manic recurrences in affective illness by means of long
      term administration of lithium salts. Subsequent several years of controlled
      studies confirmed such prophylactic effect of lithium in affective illness beyond
      any doubt. Some patients in whom lithium administration was started in the
      beginning of 1970s may, by now, have received lithium for more than twenty years.
      The patient reported in the present paper, had began lithium treatment on April
      1, 1971, after her third depressive episode since 1965. During 25 years of
      uninterrupted lithium carbonate administration in daily dose 1000 mg (for 5 years
      750 mg) and with mean serum lithium concentration 0.6 mmol/l, the recurrences
      have not been observed, mental status was normal and professional (physician
      ophthalmologist) and family functioning was good. Either somatic or mental side
      effects have not occurred. Twenty five years of the patient's lithium treatment,
      was paralleled by important events for lithium therapy such as, i.a.,
      autobiographies of prominent persons receiving lithium for porphylactic purposes,
      definition of a new category of psychotropic drugs (normothymic) with lithium as
      a prototype, establishing some mechanism of lithium action on intracellular
      transmission, discovery of antiviral and immunomodulatory effect of lithium as
      well as finding of decreased mortality of patients receiving long-term lithium
      therapy.

PMID- 8984516
TI  - [The assessment of regional cerebral blood flow using HMPAO-SPECT during
      depressive episode and in remission].
AB  - Twenty patients who met the DSM-IV criteria for major depressive disorder were
      investigated at rest using Single Photon Emission Computed Tomography (SPECT).
      Participation in the study required a minimum score of 18 points on the 17-item
      Hamilton Rating Scale. All patients were drug free for at least one week before
      the SPECT scan. Assessments were made twice during depression and after recovery.
      Regional tracer uptake was measured by a semiquantitative method. The reference
      region was delineated on the cerebellum. In remission a significant increase of
      99m Tc-uptake in almost all regions of interest was observed what may point on
      the improvement of regional blood flow after recovery from depression. For most
      regions except right frontal and left parietooccipital there were no significant
      differences of tracer uptake between patients with bipolar and unipolar
      depression. The negative correlation between regional cerebral blood flow and
      Hamilton score was found in temporal areas and left temporo-parietal region. We
      did not find the influence of age on regional cerebral blood flow. In conclusion,
      during depression global reduction of brain metabolism was observed, which may
      point on the role of subcortical nuclei with diffuse cortical projection in
      pathogenesis of depression.

PMID- 8984515
TI  - [Limbic-hypothalamic-pituitary-adrenal axis in depression: literature review].
AB  - A review of the literature has been presented concerning pathogenetic role of
      limbic-hypothalamic-pituitary-adrenal axis (LHPA) in depression and the
      therapeutic possibility obtained by influencing this axis. Increased cortisol
      concentration has until now been the best documented biochemical abnormality in
      depression. Pathological results of the Dexamethasone Suppression Test pointing
      to hyperactivity of LHPA axis are found in about half of depressive patients.
      According to most recent research, primary disturbance of LHPA axis concerns
      hypothalamus (excessive secretion of corticotropin releasing factory) and limbic
      system (insufficiency of glucocorticoid receptor). An association was found
      between disturbances of LHPA axis in depression and immune system abnormalities
      in this illness. Disturbances of serotonergic and noradrenergic neurotransmission
      in depression may also partially result from LHPA axis dysfunction. In recent
      years, the attempts have been made to use drugs acting on LHPA axis for
      therapeutic purposes in depression, such as ketoconazole, within the framework of
      antiglucocorticoid strategy. Influencing LHPA axis may underlie the mechanism of
      new antidepressant drug, tianeptine. Recently, it was found that classical
      tricyclic antidepressant drugs as well as electroconvulsive may also act on LHPA
      in regulatory way.

PMID- 8984517
TI  - [Immune activation in endogenous depression].
AB  - Serum concentration of three positive acute phase proteins: C-reactive protein
      (CRP), alpha-1-acid glycoprotein (AGP), alpha-1-antychymotrypsin (ACT) were
      measured in 81 patients with endogenous depression during acute episode and in 20
      matched controls. Determination was also made of glycosylation types of AGP and
      ACT as well as of the concentration of interleukin-6 (IL-6) and its soluble
      receptor (sIL-6R). In patients with depression, the mean values of all parameters
      studied except for AGP glycosylation were significantly elevated compared with
      the group of control healthy persons, what may suggest an excessive immune
      activation in these patients in the form of acute phase response. Particularly
      intense were the indies of the immune activation in the subgroup of patients (1/3
      of population studied) having pathologically elevated coefficient of AGP
      glycosylation (Type I glycosylation). Patients with Type I glycosylation had
      longer duration of illness and were characterized by recent depressive episode of
      greater severity and chronicity as well as refractoriness to pharmacological
      treatment. The results obtained corroborate the existence of excessive immune
      activation during acute depressive episode and suggest the possible role of this
      phenomenon in the pathogenesis and course of affective illnesses.

PMID- 8984518
TI  - [Changes of humoral and cellular immunity in schizophrenia].
AB  - The paper is a review of the literature on cellular and humoral immunity in
      schizophrenic patients. The reports have revealed that there are manifestations
      of autoimmunological process in a subgroup of schizophrenics (among others:
      increased serum level of specific and non-specific autoantibodies, decreased
      lymphocyte interleukin-2 production, increased soluble IL-2 receptor
      concentration, increased serum IL-6 level, presence of lymphocyte abnormalities
      and association with HLA antigens. It is suggested that virus infection may
      provoke the appearance of autoimmunological reaction, while genetic factors might
      increase some predisposition to this reaction. The reports have also revealed
      that autoimmunity may play a role in pathogenesis of schizophrenia in a subgroup
      of schizophrenic patients who have immunological abnormalities.

PMID- 8984519
TI  - [Immunological system activity in anorexia nervosa].
AB  - The immunological system of patients with anorexia nervosa seems to react in a
      non typical and, up to now, obscure way. We do not observe greater ability to
      catch infectious diseases while damage due to other reasons leads as a rule to
      breakdown of resistance mechanisms thus giving increased receptivity to
      infections. The works concerning the immunological functions in anorexia nervosa
      are not heterogeneous and concern small groups of patients. The research was made
      upon 29 female patients aged 12 to 20 with the diagnosis of anorexia nervosa due
      to DSM-IV criteria. The research was made before starting the treatment and 6
      weeks after the withdrawal of all anorexia nervosa symptoms. The research results
      showed that in the female patients there were no essential disturbances in the
      scope of electrophoresis of serum protein. Testing the protein of acute phase CRP
      as well as the estimation of their main microheterogeneity did not show
      significant deviation from the norm, which shows any features of early and later
      activation of the immunological system. However, a slight decrease of CD3 and low
      coefficient CD 4/8 during the disease were observed. After the symptoms retreated
      the coefficient became normal. Summing up we can state that the immunological
      system in patients with anorexia nervosa, in spite of great cachexia, did not
      show significant changes. The stated specific dysfunctions may be connected with
      a subtype of disease and other neurotransmitter mechanisms, which still requires
      to be confirmed in further research.

PMID- 8984520
TI  - [Intelligence quotient levels, aspiration and self-acceptance in patients with
      restricting and binge-eating type of anorexia nervosa].
AB  - A group of 50 patients aged from 12 to 20 with anorexia nervosa was examined: 40
      persons with a diagnosis of restricting type and 10 with binge-eating type
      according to DSM IV. The level of intelligence quotient (IQ) was estimated by
      using Wechsler Test, selfacceptation by SQ and aspiration by TAT and test of
      unfinished sentences. In the majority of patients IQ was stated on the average
      level. Independently of intellectual level all patients presented a high
      aspiration degree. In their own estimation the emotional motivation sphere was
      significantly more important in the patients with binge-eating type and
      intellectual in the patients with restricting type of anorexia nervosa.

PMID- 8984521
TI  - [The typological analysis of males with alcohol dependence disorder].
AB  - The aim of our study was the typological analysis of male alcoholics that was
      conducted on the basis of the K-means cluster analysis. 296 hospitalized men were
      examined after a duration of drinking. The results of the statistical analysis
      let us isolate two and then three types of alcoholics. When dividing the examined
      into two clusters it appeared that those who belonged to the 1st type had shorter
      history of addiction, became dependent later and in their case coexistence of
      psychiatric disorders, somatic diseases and the genetic loading for alcoholism
      were found less frequently than those from the 2nd type. Thus, early age of
      dependence onset was connected with the family alcoholism and worse clinical
      course-i.e.-co-occurrence of psychiatric disorders and somatic diseases. When
      dividing the patients into three clusters the following variables that
      differentiate the examined from three types of alcoholics were found: (a)-1st
      type: late age of dependence onset, rare load of family alcoholism, psychiatric
      disorders, somatic diseases; (b)-2nd and 3rd type: early age of dependence onset,
      the load of family-alcoholism, co-occurrence of psychiatric disorders and somatic
      diseases; (c)-3rd type: patients from the 3rd type were dependent longer than
      those from the 2nd type. Longer duration of the disease was connected with more
      frequent occurrence of psychiatric disorders and somatic diseases.

PMID- 8984522
TI  - [Typological analysis in male alcoholics: one-year-long follow-up study].
AB  - The aim of our study was to estimate the correlation between typological division
      of male alcoholics and intensity of psychopathological symptoms in one year
      follow-up study. The studies at the Department of Psychiatry in Poznan included
      82 men hospitalized after the period of drinking and examined one year after the
      treatment. The typological division of male alcoholics was the subject of another
      study and the patients included in this examination belonged to that
      investigative group. Two typological groups were isolated. The first group
      included the patients who-were characterized by late age of the disease onset,
      light load of alcoholic problems in a family, slight intensity of addiction
      profoundness, rare occurrence of psychiatric disorders and somatic diseases. The
      second group was characterized by an early age of the disease onset, profound
      addition, load of alcoholic problems in a family, frequent occurrence of somatic
      diseases and psychiatric disorders. The psychometric estimation was conducted on
      the basis of the results of the HDA, STAI XI, X2 scales. It was found out that
      the attachment to a typological group was not connected with maintaining of
      abstinence in one-glow follow-up study. In one year follow-up study the patients
      who belonged to the second typological group were characterized by higher
      intensity of depressive symptoms.

PMID- 8984523
TI  - [Professor Wlodzimierz Strzyzewski: physician, scientist, academician].

PMID- 8984524
TI  - Papers from the Boden Research Conference on Marsupial Gametes and Embryos. New
      South Wales, 1-4 February 1995.

PMID- 8984525
TI  - Pharmacotherapy of respiratory muscles in chronic obstructive pulmonary disease.

PMID- 8984526
TI  - Transient increases in albumin and hyaluronan in bronchoalveolar lavage fluid
      after quitting smoking: possible signs of reparative mechanisms.
AB  - Inhalation of tobacco smoke results in an accumulation of cells in the lower
      respiratory tract. The inflammatory response in the alveoli and lung interstitium
      may also be reflected by increased bronchoalveolar lavage (BAL) fluid
      concentrations of extracellular matrix components. The present study investigated
      the influence of smoking on the BAL fluid concentrations of albumin (ALB),
      hyaluronan (HA) and fibronectin (FN). Lavage fluids from 18 smokers were analysed
      before and at 1, 3, 6, 9 and 15 months after smoking cessation. Never-smokers (n
      = 112) served as a reference group. The total cell concentration and the
      concentrations of macrophages, lymphocytes, neutrophils and eosinophils were
      higher (P < 0.001-0.01) in smokers' BAL fluid than in never-smokers', but the
      values returned to normal within 9 months of smoking cessation. The HA
      concentration was higher (P < 0.001) in smokers' than in never-smokers' BAL
      fluid, but FN and ALB did not differ. Transient increases in the concentrations
      of ALB and HA (P < 0.01 for both) was observed within 6 months of smoking
      cessation. These findings indicate a temporary heightened alveolar-capillary
      permeability and an increased production and/or degradation of HA, being enhanced
      following smoking cessation. The findings probably reflect an initiation of a
      reparative process.

PMID- 8984527
TI  - Predictors of Staphylococcus aureus pneumonia associated with human
      immunodeficiency virus infection.
AB  - This study is based on a retrospective logistic regression analysis of all human
      immunodeficiency virus (HIV)-infected patients with Staphylococcus aureus
      pneumonia (SAP) admitted to the Department of Infectious Diseases, Catholic
      University, Rome, Italy between January 1986 and December 1994. Nineteen patients
      with 24 episodes of SAP were enrolled in the study. A control group of 38 HIV
      infected patients without pneumonia was included. The attack rate of SAP was
      8.31/1000 HIV-related hospital admissions and the frequency, out of the total
      number of bacterial pneumonia observed in the study period, was 16% (24 of 154
      patients). The large majority of SAP was community acquired. On the univariate
      analysis, intravenous drug abuse (IVDA) (P = 0.02), history of previous
      Pneumocystis carinii pneumonia (PCP) (P = 0.03) and cirrhosis (P = 0.03) were
      significant risk factors for SAP. In addition, IVDA and previous PCP were
      independent risk factors on multivariate analysis. All patients presented with
      fever associated with cough (74%), chest pain (26%) or shortness of breath (37%).
      Chest X-ray documented lobar pneumonia (78%), predominantly in the lower lobes,
      consolidation with cavitation (11%), and interstitial-nodular infiltrates (11%).
      Pleural effusion was present in 31% of patients. The response to therapy was
      favourable in 79% of patients. Recurrence occurred in 26% and death occurred in
      21% of patients. Death was significantly associated with the low level (< 50 mm
      3) of circulating T CD4+ cells (P = 0.03) and the recurrence of pneumonia (P =
      0.03). In conclusion, the present study indicates that S. aureus is an important
      aetiologic agent of bacterial pneumonia in HIV-infected patients, especially if
      they are drug abusers with previous PCP.

PMID- 8984528
TI  - Comparison of the process of care of acute severe asthma in adults admitted to
      hospital before and 1 yr after the publication of national guidelines.
AB  - This study set out to assess the effect of publication of the British Guidelines
      on Asthma Management on the processes and outcomes of the inpatient care of acute
      severe asthma in the U.K. A criterion-based audit of all acute asthma admissions
      during August and September 1990 (immediately before) and in 1991 (1 yr after
      publication of the Guidelines) using eight criteria of process and outcome was
      performed. Thirty-six teaching and district general hospitals in England,
      Scotland and Wales took part. In total, 766 patients admitted in 1990, and 900
      patients admitted in 1991, were studied. The 1990 and 1991 cohorts were very
      similar demographically and had asthma of comparable severity. Respiratory
      physicians achieved similar high performance rates of between 75 and 91% for
      seven of the eight criteria for both years. Respiratory physicians were
      significantly more likely to provide patients with a written management plan in
      1991. General physicians' performance was significantly lower in both years, but
      overall there was a very small, but just significant, improvement in their
      performance in 1991. Some hospitals performed consistently well in both years. It
      is concluded that respiratory physicians consistently provide better asthma care
      than general physicians. Though statistically significant, the small degree of
      improvement was disappointing. Possible reasons include: insufficient time for
      the Guidelines to be incorporated into practice; inaccessibility of the
      Guidelines to general physicians; failure to accept responsibility for
      implementing the good practice reflected in the Guidelines; and an explicit need
      for strategies to implement the Guidelines beyond publication in a widely-read
      general medical journal.

PMID- 8984529
TI  - Pulmonary interstitial fibrosis and haemosiderin-laden macrophages: late
      following heart transplantation.
AB  - Impairment of pulmonary diffusion is recognized following heart transplantation.
      This study was undertaken to determine the histopathological basis for the defect
      in pulmonary physiology. Heart transplant recipients (HTR) entered into a
      prospective study of post-transplant pulmonary physiology were asked to undergo
      bronchoscopy, bronchoalveolar lavage (BAL) and transbronchial biopsy (n = 18) in
      the presence of impaired gas transfer. Transbronchial biopsies were examined
      under light microscopy and demonstrated focal interstitial fibrosis in 12
      patients, cytomegalovirus disease in four patients and Pneumocystis carinii
      pneumonia in three patients. Bronchoalveolar lavage differential counts were
      normal in HTR but BAL macrophages contained haemosiderin. The histological
      features of interstitial fibrosis may underlie the fall in gas transfer seen
      following heart transplantation. The presence of haemosiderin-laden macrophages
      late following heart transplantation suggests a capillary leak syndrome.

PMID- 8984530
TI  - Single lung transplantation for chronic obstructive pulmonary disease: pulmonary
      function and impact of bronchiolitis obliterans syndrome.
AB  - Chronic obstructive pulmonary disease (COPD) is now the most common indication
      for single lung transplantation. In long-term follow-up, obliterative
      bronchiolitis is a major problem. The aim of the present study was to perform a
      long-term follow-up of the pulmonary function and to examine the effect of
      development of bronchiolitis obliterans syndrome (BOS). Nineteen patients with
      end-stage COPD underwent single lung transplantation and were followed regularly
      with pulmonary function tests, and ventilation and perfusion scintigraphy (mean
      observation time 29 months). They were divided into two categories, with and
      without BOS, using the definition recommended by the International Society for
      Heart and Lung Transplantation working group. A mixed model analysis of variance
      with BOS as co-variate was used to evaluate its effect on pulmonary function.
      Spirometry, lung transfer factor for carbon monoxide (TLCO), arterial blood gases
      and 6-min walk test improved significantly (P < 0.001) from before
      transplantation to 3 months after transplantation. Nine patients developed BOS.
      Implied by the definition of the syndrome, forced expiratory volume in 1 s (FEV1)
      was significantly (P < 0.001) lower for patients with BOS while there was no
      significant effect of BOS category on TLCO corrected for alveolar volume (VA) or
      perfusion to transplant. Patients without BOS maintained their pulmonary
      function, and ventilation and perfusion to transplant for more than 3 yr after
      transplantation. The present results suggest that decreasing FEV1 accompanied by
      an unchanged TLCO/VA and pulmonary perfusion support the diagnosis of BOS after
      single lung transplantation for COPD.

PMID- 8984532
TI  - Left recurrent nerve paralysis associated with complete lung collapse with
      consolidation in an adult with cystic fibrosis.

PMID- 8984531
TI  - A long-term study of symptoms, spirometry and survival amongst home nebulizer
      users.
AB  - Although home nebulizers are widely used to deliver bronchodilator medication to
      patients with asthma and chronic obstructive pulmonary disease (COPD), the long
      term benefits and hazards are unknown. The present authors have previously
      reported a prospective 12-month study of home nebulizer use involving 49 patients
      (15 asthma, mean forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC)
      1.3/2.1 1; 34 COPD, mean FEV1/FVC 0.7/1.8 1). Thirty-two of these patients were
      treated with long-term domiciliary nebulized bronchodilator treatment, the other
      17 patients chose metered dose inhaler (MDI) therapy. The present paper reports
      the progress of these patients over 5 yr. Five-year survival was similar in both
      groups (nebulizer users 56%, MDI users 53%). Most deaths were due to respiratory
      failure (14 deaths) or lung cancer (four deaths). Survival was determined mainly
      by FEV1 (R = 0.54, P = 0.0001) and age (R = -0.47, P = 0.0007). Laboratory lung
      function tests (16 nebulizer users) showed that FEV1 and FVC were still higher
      than pre-nebulizer baseline measurements after 36 months of nebulizer use, but
      PEFR had fallen by 7%. Twenty-one of 23 surviving nebulizer users completed a
      questionnaire after 36 months of treatment. All used their nebulizer at least
      once per day and 20 of 21 patients reported that they still obtained full benefit
      from each nebulized treatment. The morning peak flow response to nebulized
      treatment was the same at baseline and at 36 months (48 1 min-1). All patients
      remained breathless (mean subjective score 4.8 on seven-point scale) but the
      subjective response to nebulized treatment was unchanged at 36 months.
      Tachyphylaxis did not develop among 13 patients who underwent repeated
      reversibility studies using 200 micrograms of salbutamol at 6, 12 and 36 months.
      It is concluded that home nebulizer therapy is safe and effective for a small
      number of carefully selected patients with severe asthma or COPD, who have been
      evaluated by a rigorous home nebulizer assessment protocol prior to commencing
      home nebulizer therapy.

PMID- 8984533
TI  - Temporary obstructive apnoea syndrome attributed to cryptococcus (meningo)
      encephalitis.

PMID- 8984534
TI  - [Excipients and their problems in therapeutics].

PMID- 8984535
TI  - [Nutrient and food consumption by ages and gender in school children from the
      Community of Madrid (CAENPE)].
AB  - The objective of the present work was to know the consume of foodstuffs and
      nutrients among schoolchildren in the Madrid Autonomous Community and also the
      relative contribution of each group of foodstuffs to the overall intake of
      macronutrients. This study had a sectional observational design involving 2,608
      children (51% males and 49% females) with ages ranging from 6 to 14 years who
      were randomly recruited from conglomerate of schools, according to socio-economic
      status and rural/urban residence. The inquiry on nutrients in 4 non consecutive
      days was analyzed (2 "24 hour-recall" and 2 "intake recall"). RESULTS: a) the
      consume of proteins, lipids, and carbohydrates represented 17%, 43% and 40% of
      the total caloric value, respectively; b) the intake of meats, sausages, sweets,
      tidbits, and processed products was very high. This fact is in origin of the
      excessive total and saturated lipid intake; c) there was a scarce intake of
      vegetables, cereals and potatoes among children of all ages and dairy products in
      children older than 12 years; d) the intake of legumes, eggs and fruits was
      appropriate; e) males consumed proportionally higher amounts than females of the
      following groups of foodstuffs: cereals, sweets and tidbits. The consume of meat,
      sausages, fish, eggs, potatoes, dry fruits and dairy products was similar in both
      sexes. Females consumed proportionally more fat foodstuffs, vegetables, fruits,
      legumes and processed products; f) females consumed a diet with a still higher
      lipid and protein content than males. These findings can serve as a basis to
      develop educational guidelines with a practical impact on family and school
      menus.

PMID- 8984536
TI  - [Level of compliance in the treatment of sleep obstructive apnea syndrome with
      nasal continuous positive pressure].
AB  - The therapy of the obstructive sleep apnea syndrome (OSAS) with nasal continuous
      positive airway pressure (CPAP) eliminates symptoms of OSAS and is currently the
      non-surgical therapy of choice. The present study was undertaken to evaluate the
      compliance with such therapy in our setting, the factors associated with it, and
      the secondary effects. A sample of 88 patients diagnosed with OSAS and undergoing
      CPAP followed for a period of 29 +/- 11 months was studied. The results showed
      that compliance among our patients, as measured by time counter, was 70% and was
      associated with drowsiness degree, apnea/hypopnea index, and mean pressure of
      CPAP. The subjective evaluation of compliance by patients overestimates the
      actual use of the CPAP device. There was a high satisfaction degree with therapy,
      and secondary effects were not a limiting factor for compliance. The
      therapeutical approach of the patient must be on an individual basis if a good
      acceptance level is to be achieved.

PMID- 8984537
TI  - [Imipenem combined with teicoplanin or vancomycin in the initial empirical
      treatment of febrile neutropenia. Analysis of the primary response and of a
      global sequential strategy in 126 episodes].
AB  - The results of empiric antibiotic therapy in 126 episodes of febrile neutropenia
      in patients with hematologic neoplasms postchemotherapy and bone marrow
      transplantation are presented. The main objective of this work was the study of
      the initial control of infection comparing two glycopeptidic antibiotics:
      vancomycin and teicoplanin combined with imipenem in first line of empiric
      therapy. The secondary objective was to analyze the overall control of infection
      during the complete episode of neutropenia using a sequential empiric antibiotic
      therapy course which included the addition of amikacin followed by intravenous
      amphotericin B when fever persisted or recurred without microbiological
      documentation. Both initial courses (no guidelines), imipenem + vancomycin (arm
      A) and imipenem + teicoplanin (arm B) resulted in a similar percentage of
      response at 72 hours, both in episodes of fever of unknown origin (FUO) (55% and
      68%, respectively; p = NS) and in those microbiologically documented (54% and
      34.5%, p = NS); 58% and 79% of these episodes, respectively, were caused by gram
      positive organisms. About 60% of patients in both arm ultimately required the
      empiric addition of amikacin, with or without amphotericin B, because of
      persistence or recurrence of fever; the percentage of overall responses in both
      arm did not differ significantly, both in FUO (70% and 86%, p = NS) and in
      microbiologically documented episodes (71% and 45%, p = NS). The overall
      infectious mortality for the whole group was 1.58%. In conclusion, no significant
      differences were observed in the clinical response or in toxicity between the
      combination of imipenem with any of the two glycopeptides: vancomycin or
      teicoplanin, for the initial empiric therapy of febrile neutropenia. The
      sequential empiric use of amikacin followed by amphotericin B assured an adequate
      overall control of infection in a group of patients with prolonged severe
      neutropenia.

PMID- 8984538
TI  - [Do physicians know the cost of the treatments and tests they prescribe?].
AB  - OBJECTIVE: To determine the degree of knowledge among physicians regarding the
      cost of diagnostic tests and commonly used drugs. INDIVIDUALS AND METHODS: An
      interview was obtained with a representative sample of 164 physicians from a
      total of 338 (accuracy +/- 3.55), distributed in interns/residents (n:119) and
      staff members (n:45) from the divisions of Surgery (n:81) and Medicine (n:83) at
      Hospital Clinic i Provincial, Barcelona. The questionnaire included 15 questions,
      10 regarding drugs and 5 diagnostic tests, with 5 possible answers. An arbitrary
      scoring system was used (correct answer: 5 points; approximate; 3 points;
      mistake: 1 point) and the percentage of right answers (correct and approximate
      answers) was also evaluated versus mistakes. The Student "t" test, the analysis
      of variance and the chi 2 test were used to compare the results. RESULTS: The
      overall score reached was 2.72 +/- 0.41. Differences between residents vs staff
      and medicine vs surgery were not significant. The score in questions regarding
      diagnostic tests was significantly higher than that obtained for drug cost among
      all group. The percentages of right answers (correct and approximate answers)
      were 58.8%-61.7% (drugs) and 58.3-60.8% (tests), with no differences among
      groups. Differences regarding year of residence were also not significant.
      CONCLUSIONS: The knowledge degree on costs of some drugs and diagnostic tests
      among physicians is deficient. It is necessary to find standards that contribute
      to increase the level of information regarding costs derived from the health care
      delivery process among health care professionals.

PMID- 8984539
TI  - [Isotypic characterization of IgA paraproteins: association with other clinical
      and analytic data].
AB  - A study was conducted to investigate the relationships between the
      characteristics of IgA paraprotein and the clinical findings in a group of 196
      patients. In 19 cases IgA paraprotein was associated with another monoclonal
      immunoglobulin (IgG or IgM); the other 177 patients had a single IgA paraprotein;
      145 of them corresponded to multiple myeloma (MM) and the other 32 to other
      diagnostics. Class and type of paraproteins were identified by
      immunoelectrophoresis and subclass by an enzyme-immunoassay specifically
      developed for this study. The degree of polymerization of the protein was
      determined by gel filtration; quantitation of monoclonal IgA and polyclonal IgG
      and IgM was obtained by kinetic nephelometry. Out of 196 paraproteins, 96.4% were
      classified in IgA1 subclass and only 3.6% in IgG2. In 14 cases, all of them
      diagnosed with MM, monoclonal IgA in serum was associated with Bence-Jones
      protein; in more than 78% of them light chains corresponded to type lambda,
      whereas type kappa predominated (over 60%) in cases without Bence-Jones protein
      in serum. Significantly higher serum levels of monoclonal IgA were associated
      with the diagnosis of myeloma, with type kappa paraproteins, and with the
      presence of Bence-Jones protein in serum. The cases with two paraproteins (IgA
      and IgG or IgM) had significantly lower serum levels of IgA, with comparable
      levels of total paraprotein (the addition of both monoclonal immunoglobulins).
      Serum levels of polyclonal IgG and IgM, which appeared decreased in cases of MM,
      were normal in cases with other conditions. In all these cases, monoclonal IgA
      showed a monomeric character, whereas relevant amounts of polymerized IgA
      paraprotein was found in almost a third part of myeloma cases, particularly in
      those with higher serum levels of paraprotein, or when paraprotein belonged to
      type kappa. The 5 IgA2 paraproteins analyzed had a polymeric character. In
      conclusion, a detailed, both qualitative and quantitative, analysis of IgA
      paraproteins can lead to a better knowledge of conditions associated with their
      presence and at the same time provides useful data for a clinical evaluation of
      patients.

PMID- 8984540
TI  - [Graves Basedow disease following treatment with magistral formulae for obesity.
      Jod-Basedow phenomenon?].
AB  - Two cases are reported of women aged 18 and 36 years respectively who developed a
      typical picture of hyperthyroidism by Graves Basedow disease (primary
      hyperthyroidism, diffuse goiter with increased uptake, positive stimulating
      thyroid antibodies, exophthalmos). These women had taken drugs for obesity which
      were prepared by magistral formula and acquired by mail 8 and 9 months prior to
      diagnosis of the disease. The differential diagnosis is discussed which should be
      considered in a women with hyperthyroidism and the antecedent of ingestion of
      weight-reducer drugs as well as the orientative data of the different causes.
      Also, the possible role of these drugs as triggering factor for the autoimmune
      thyroid disease is discussed.

PMID- 8984541
TI  - [Polyarthritis associated with myelodysplastic syndromes].
AB  - Recently, different rheumatic manifestations have been reported in association
      with myelodysplastic syndromes (MDS). The objective of the present report was to
      know the prevalence and characteristics of joint inflammatory manifestations
      associated with MDS in our environment. Three cases were found in the review of
      55 patients with MDS diagnosed in our institution in the last three years. The
      three patients had chronic non-erosive polyarthritis, with a poor response to non
      steroidal anti-inflammatory drugs and required intermediate doses of
      glucocorticoids for its control. The arthritis was present in two patients at
      blood disease diagnosis. The prevalence of arthritis associated with MDS in our
      series was 5.4% (95% CI: 1.1% to 15.1%). Articular symptoms may be present before
      the hematological diagnosis; therefore, MDS must be considered in the
      differential diagnosis of late onset polyarthritis, particularly when associated
      with cytopenia. Glucocorticoid therapy at intermediate doses is usually required
      to control the articular symptoms.

PMID- 8984542
TI  - [Local infectious complications in acute pancreatitis].

PMID- 8984543
TI  - [Mediterranean diet in Spain. Legend or reality? (I). Study of 7 countries.
      Various elements of the Mediterranean diet: olive oil and red wine].

PMID- 8984544
TI  - [Atelectasis and active pulmonary tuberculosis in an 18-year-old male].

PMID- 8984545
TI  - [Volume increase of the left thigh in a patient with Paget's disease].

PMID- 8984546
TI  - [Mediastinal enlargement with upper esophageal impression].

PMID- 8984547
TI  - [Progressive abdominal distension and shock following cardiorespiratory arrest].

PMID- 8984548
TI  - [Heart failure, arterial hypertension, and hypokalemic alkalosis].

PMID- 8984549
TI  - [Thoracic pain of 2 month duration].

PMID- 8984550
TI  - [Vitamin C deficiency and hemorrhagic syndrome].

PMID- 8984552
TI  - [Treatment of essential thrombocytopenia associated with severe renal
      insufficiency].

PMID- 8984551
TI  - [Epstein-Barr virus primary infection: a poorly known cause of acute genital
      ulcer. Lipschutz ulcer?].

PMID- 8984553
TI  - [Eustachian valve endocarditis produced by Staphylococcus hominis in a patient
      with HIV infection].

PMID- 8984554
TI  - [Pharma clinics. How I treat... Falciform anemia in children].

PMID- 8984556
TI  - [Paradoxical human sleep].

PMID- 8984555
TI  - [The value of renal angioscintigraphy with captopril administration in
      renovascular hypertension].

PMID- 8984557
TI  - [Role of hormone substitution treatment following breast cancer].

PMID- 8984558
TI  - [Noninvasive ventilation at 2 pressure levels (VNI-2P or Bi-PAP)].

PMID- 8984559
TI  - [A frequently unrecognized cause of vascular lesions: Behcet's disease].

PMID- 8984560
TI  - [Will ecology, photo-climatology and geography affect tomorrow's dermatology?].

PMID- 8984561
TI  - [Prevention of postmenopausal osteoporosis: estrogens and nonhormonal drugs].

PMID- 8984562
TI  - [Prevention of coronary disease in clinical practice: summary for clinicians].

PMID- 8984563
TI  - [How I explore... insulin secretion in clinical practice].

PMID- 8984564
TI  - [Pharma-clinics. Drug of the month. Risperidone (Risperdal)].

PMID- 8984565
TI  - [Congress information. Clinical benefits of the use of a statin following
      myocardial infarction in patients without frank hypercholesterolemia].

PMID- 8984566
TI  - [What is your diagnosis? Scapholunar dissociation (rotation subluxation of the
      scaphoid)].

PMID- 8984567
TI  - [Anorectal physiological tests: indication and relevance].

PMID- 8984568
TI  - [Drug-induced taste disorders].
AB  - Taste disorders may have diverse uncomfortable consequences such as reduced
      quality of life, weight loss and possibly professional disability. The sense of
      taste depends on many factors. Thus various conditions may cause taste disorders,
      drugs being one of them. The list of drugs being able to cause taste disorders as
      adverse drug reaction is long and there are many such cases reported to the Swiss
      Drug Monitoring Center (SANZ). The possibility of an unwanted side effect should
      be taken into account if a patient complains about taste disorders, such as
      reduced or changed sense of taste.

PMID- 8984569
TI  - [How did the AIDS virus develop? Scientific knowledge and philosophical
      suppositions].
AB  - Several years after the occurrence of the first cases of AIDS, the HIV retrovirus
      was discovered in the eighties. How did this terrible virus come into being? 'A
      punishment from God' say some. 'A new life form created by man using gene
      technology', say others. Most scientists, however, do not share these views. They
      assume that spontaneous, random gene mutations are responsible for the AIDS
      virus. Viruses change their qualities frequently and new variations are
      constantly being created. Some philosophical conclusions from these findings are
      discussed.

PMID- 8984570
TI  - [Optimization of the Barron ligature treatment of 2nd and 3rd-degree hemorrhoids
      using a therapeutic troika].
AB  - Due to the fact that the intensity of haemorrhoidal complaints may rapidly
      change, also numerous therapeutic approaches of minor effectiveness are
      considered a helpful remedy. However, the advantage of the Barron-ligature is not
      seriously doubted. By placing it correctly at the insensitive distal rectum,
      haemorrhoidal operations are only necessary in very advanced stages. Can the
      Barron ligature be optimized even more? Three patient groups consisting of 120
      patients with 2nd degree haemorrhoids who were simultaneously treated by anal
      dilation using an appropriate lubricant for the anal dilator, were compared with
      each other in a randomized, open, placebo-controlled study conducted in two
      centres. In these groups treatment consisted of: rubber-band ligature alone
      rubber-band ligature and anal dilator and Kamillosan ointment rubber-band
      ligature and anal dilator and vaseline The observation period comprised six
      weeks. Every two weeks a check was made. Assessment criteria were: light-red
      haemorrhage, itching, oozing, sensation of incomplete evacuation, nodal prolapse
      and slight staining after defecation The pressure ratios of the closing apparatus
      were investigated at the beginning and end of the study. The group who had been
      treated with rubber-band ligature, anal dilator and Kamillosan ointment showed
      the best results. By simultaneously applying the rubber-band ligature, anal
      dilator and Kamillosan ointment as a lubricant, significantly better results
      could be obtained. The findings are based on a former retrospective study carried
      out in 500 patients with 2nd degree haemorrhoids. In this study by applying the
      anal dilator and Kamillosan ointment, the number of treatments could
      significantly be reduced from 5.95 to 4.2 and the number of necessary ligatures
      from 3.8 to 2.76 which, also from the economic point of view, was favourable.

PMID- 8984571
TI  - [Syncope in elderly patients--which studies are sensible?].
AB  - In the elderly the cause of a syncope often is difficult to elucidate. A
      prospective study at the Kantonsspital Liestal (Switzerland) confirmed that
      history and physical examination together with an ECG at rest are the most
      important diagnostic tools in the investigation of a syncope. Further
      investigations such as 24-hour ECG, echocardiography or tilt test should be
      restricted to situations where history and physical examination support the
      suspicion of rhythm disturbances or valvular disorder or a vasovagal mechanism.
      Thus, if an arrhythmia is suspected a 24-hour ECG may produce useful information.
      Implantable pacemakers are particularly successful in bradycardic arrhythmias.
      Echocardiography and Doppler-ECG allow to quantify the severity of an aortic
      stenosis. The insertion of a prosthetic aortic valve is successfully performed
      also in the elderly. Tilt testing may elucidate the neurocardiogenic mechanism of
      a vasovagal syncope or a hypersensitive carotis sinus. In such cases a pacemaker
      or appropriate medication may be indicated.

PMID- 8984572
TI  - [The clinicopharmacological case (5). serotonin reuptake inhibitor and 5-HT3
      receptor antagonists: are there clinically relevant interactions?].
AB  - We describe a patient with chronic depression who was treated with the selective
      serotonin-reuptake-inhibitor sertraline. Following surgery, the patient developed
      severe nausea and vomiting, necessitating an efficient antiemetic treatment,
      possibly including the 5-HT3-receptor antagonist ondansetrone. Because both
      drugs, sertraline and ondansetrone, interact with the serotonin system at the
      synapsis, a possible interaction was discussed. Since the effect of the selective
      serotonin-reuptake inhibitors mainly depends on 5-HT1 and 5-HT2-receptors, a
      pharmacodynamic interaction between an 5-HT3-antagonist and a serotonin-reuptake
      inhibitor at the synapsis leading to the relapse of depression seems to be very
      unlikely. There exist also no conclusive data suggesting a clinically relevant
      pharmacokinetic interaction between the two drugs. A treatment with ondansetrone
      was considered to be safe in this patient.

PMID- 8984573
TI  - [A case from practice (361). Acute pancreatitis in AIDS. idiopathic. In
      microscopic gallstones. (Cotrimoxazole-induced). (In cryptosporidiosis)].

PMID- 8984574
TI  - [A case from practice (362). Early summer meningitis. FSME-IgG and IgM-positive.
      No vaccine prophylaxis. Place of infection very possible Stein am Rhein (Ch).
      Parainfectious stomatitis under antibiotic treatment].

PMID- 8984575
TI  - [What is your diagnosis? Stress fracture of the right iliac wing].

PMID- 8984576
TI  - [Current diagnosis of viral hepatitis].
AB  - The structure and genetic organization of the hepatitis viruses A-E are well
      characterized. HAV and HEV cause acute and sometimes fulminant hepatitis. By
      contrast, HBV, HCV and HDV infections frequently progress to chronic hepatitis,
      liver cirrhosis and hepatocellular carcinoma (HCC). The specific detection of the
      hepatitis viruses A-E is based on serological and molecular analyses. In clinical
      practice, it is possible in most cases to identify the viral infection by a
      single serological screening test. In particular clinical situations, the
      diagnostic workup requires additional serological or molecular analyses. Given
      the different diagnostic tests, it is possible today to specifically identify the
      etiologic agent in most patients with acute or chronic viral hepatitis.

PMID- 8984577
TI  - [Current diagnosis of chronic nonviral hepatitis].
AB  - Apart from viruses, hepatotoxins, hereditary metabolic disorders, immunological
      factors and cholestasis may cause chronic hepatitis both clinically and
      histologically. As far as the etiology is concerned, a complete history can be
      very helpful. The clinical examination, however, is rarely diagnostic.
      Nevertheless, some clinical signs (e.g. ascites, splenomegaly, spider naevi) are
      suggestive of cirrhosis. The activities of gammaglutamyl transferase and ALT in
      the serum are augmented in most of the patients with chronic hepatitis
      independent of its etiology. Electrophoresis reveals disturbance of serum albumin
      and globulin ratios. "Basic' laboratory tests are supplemented by carefully
      selected additional investigations (e.g. immunological tests) according to the
      history and clinical data of the individual patient. Retrograde cholangiography
      is diagnostic in the majority of patients suffering from primary-sclerosing
      cholangitis. Liver histology, best obtained during laparoscopy, allows
      classification (and prognosis) of the underlying liver disease in many patients.
      Results of iron and copper determination in liver tissue are diagnostic in cases
      of congenital liver disease (hemochromatosis, M. Wilson).

PMID- 8984578
TI  - [Current diagnosis: hereditary metabolic diseases of the liver (primary
      hemochromatosis, Wilson disease)].
AB  - Primary hemochromatosis is characterized by a specific pattern of clinical
      manifestations. It includes liver disease with hepatomegaly, glucose intolerance,
      e.g. diabetes, hyperpigmentation oft the skin, impotence/ amenorrhea,
      arthropathy, cardiomyopathy and fatigue. Laboratory investigation reveals
      significantly elevated serum ferritin and transferrin saturation with iron. The
      diagnosis is confirmed by liver biopsy and quantitative determination of elevated
      liver iron content. Wilson's disease represents a copper storage disease.
      Prominent clinical features are hepatomegaly and splenomegaly. Neurological
      alterations and detection of Kayser-Fleischer corneal rings are typical. In the
      acute initial phase the often young patients present with Coombs-negative
      hemolysis. Psychiatric alterations, cardiomyopathy, arthropathy, nephropathy, as
      well as thrombocytopenia and leucopenia are other clinical features. Laboratory
      parameters of Wilson's disease include low serum ceruloplasmin and serum copper.
      There is an elevated urinary copper excretion and elevated serum free copper
      concentration. The diagnosis is confirmed by liver biopsy with quantitative
      determination of an elevated liver copper content.

PMID- 8984579
TI  - [Space-occupying lesions in the liver--rational step-wise diagnosis].
AB  - For high diagnostic quality, it is crucial that the examiner has an exact
      knowledge of the liver tumor pathology in order to search for characteristic
      criteria. On the other hand knowledge of the overall spectrum of all diagnostic
      possibilities would also be necessary, for isolated cases, i.e. to be able to
      select in an individual clinical situation the critical investigation or the
      efficient sequence of investigations, in order to produce a swift and reliable
      diagnosis. With it, however, comes the aggravation of perpetual technical
      improvements in the tomographic imaging technique, and a wide variety of contrast
      mediums are constantly being developed and introduced, causing continuous
      problems in taking the right decision.

PMID- 8984580
TI  - [Current diagnosis of liver diseases: duplex ultrasonography].
AB  - In the last 20 years abdominal sonography has become a powerful method in
      diagnosing diseases in gastroenterology and hepatology. Now, Doppler techniques
      are also used for the examination of abdominal vessels and especially of the
      portal circulation in an increasing number of medical centers. Color Doppler flow
      imaging (CDFI) represents an extension of duplex sonography as it makes velocity
      informations available not only for a small region but also for a larger segment
      or even for the whole image. CDFI indications include all aspects of portal
      hypertension, liver diseases of unknown origin, and focal liver lesions
      suspicious for hepatocellular carcinoma. This technique when used by skilled
      operators provides much information that sometimes cannot be gained in any other
      way. The CDFI will become a complementary procedure as well as an important
      alternative to angiographic methods in the diagnosis of vascular disturbances in
      the portal system.

PMID- 8984581
TI  - A genetic study of a Staphylococus aureus plasmid involving cure and
      transference.
AB  - High frequency transfer and elimination of drug resistance may indicate an
      extrachromosomal inheritance of genetic determinants. This study shows the cure
      and transfer of a small plasmid and tetracycline resistance in Staphylococcus
      aureus 1030 (55)Tet strains. Several methods are available for plasmid
      elimination. We used ethidium bromide, an agent that binds to DNA, and thus
      inhibits DNA polymerase. This caused a high frequency of loss of the small
      plasmid and resistance to tetracycline. Transfer of tetracycline resistance was
      done in a mixed culture at a frequency of 10(-6). This type of study is very
      important to physicians and epidemiology investigators and provides better
      knowledge on antibiotic-resistance mechanisms that may occur in vivo in a
      hospital environment.

PMID- 8984582
TI  - The effects of long-term administration of guarana on the cognition of normal,
      elderly volunteers.
AB  - Paulinia cupana (guarana) is a Brazilian plant given great prestige in popular
      medicine, for example as being a potent stimulator of brain functions. The
      authors assessed the effects of the long-term administration of guarana on the
      cognition of normal, elderly volunteers. Forty-five volunteers were studied, with
      a random distribution in three experimental groups: placebo (n = 15), caffeine (n
      = 15), and guarana (n = 15), in a double-blind study. There were no significant
      cognitive alterations in these volunteers.

PMID- 8984583
TI  - Surgical treatment of noniatrogenic trauma of the femoral arteries.
AB  - Trauma to the femoral arteries corresponds to 30 percent of all arterial traumas.
      The authors reviewed 74 patients with noniatrogenic trauma of the femoral
      arteries treated from January 1991 to December 1993. Ages ranged from 11 to 50
      years, with a mean of 24. Seventy-one patients were male and three female. Fifty
      two patients (70.2 percent) were white, 20 (27 percent) were black and two (2.8
      percent) were Asian. Trauma due to firearms had the highest incidence, with 61
      cases (82.4 percent). Absence of pulse was the most frequent clinical symptom
      (62.5 percent). Severe ischemia, with risk of loss of limb, was found in 66.2
      percent of the cases. The superficial femoral artery was impaired in 77 percent
      of the cases. A preoperative arteriography was performed on only five patients,
      victims of multiple penetrating trauma or an asymptomatic penetrating wound along
      a vessel passage. In six cases, arterial and venous ligature was the chosen
      procedure. In three cases, a primary arterial anantomosis was performed. Simple
      arterriorraphy was feasible in one patient. In 64 of the patients, a venous graft
      was undertaken using a segment of the inverted great saphenous vein withdrawn
      from the other lower limb. Fasciotomoy was used in 32 patients (43.2 percent),
      all of whom exhibited pasting of the lower limb muscles at admission. One patient
      died during the immediate postoperative period as the result of multiple organ
      failure caused by polytraumatism. Preservation of the limb was attained in 72
      patients (97.3 percent) Severe, previously-incurred ischemia was responsible for
      the only two amputations, aggravated by an exceedingly long delay between the
      time of injury and surgery. One of these patients, in addition to severe
      ischemia, had extensive injuries to the soft tissues. We conclude that trauma of
      the femoral arteries, attended while the limb still maintains its vitality, has a
      positive clinical outcome with a high rate of limb preservation. Mortality
      usually results from injury to other organs.

PMID- 8984584
TI  - Chronic myeloid leukemia (CML): prognostic factors and survival analysis.
AB  - The prognostic value of different factors upon diagnosis of CML was analysed in
      45 Philadelphia (Ph1)-positive patients. The median survival was 48 months.
      Univariate analysis showed 5 poor prognostic factors (male sex, under 45 years
      old, bone marrow blasts greater than or equal to 10 percent, blood basophils
      greater than or equal to 6 percent and blood eosinophils greater than or equal to
      6 percent) which provided for the development of a clinical staging system: Stage
      I with none or one factor and a two-year survival rate of 100 percent; Stage II
      with two or three factors and two-year survival of 72.2 percent; and Stage III
      with four or five factors and two-year survival of 0 percent (p = 0.00016).
      Multivariate survival analysis showed that combination of blood basophilia and
      bone marrow blasts had the strongest predictive relationship to survival time. We
      conclude that a combination of pretreatment factors identifies different risk
      subcategories in CML patients and is helpful in assessing the overall prognosis
      and the treatment approach.

PMID- 8984585
TI  - Tomographic aspects of xanthogranulomatous pyelonephritis and related
      complications.
AB  - The authors present their experience involving seven patients with
      histopathologic diagnosis of xanthogranulomatous pyelonephritis who were
      submitted to preoperative computed tomography (CT). The results are the
      following: a) stones (86 percent of the cases), b) increase in renal volume, c)
      hydronephrosis, d) density measurements (from 14 to 29 HU), e) enhancement found
      in all cases, f) extrarenal involvement (all cases). CT has shown to be a
      reliable method in characterizing xanthogranulomatous xyelonephritis and
      extrarenal involvement.

PMID- 8984586
TI  - Inguinal hernia incarceration as a form of intestinal tuberculosis.
AB  - We report the case of a 41 year-old male who came to the emergency room with a
      complaint of abdominal pain, and was diagnosed to have an acute obstructive
      abdomen due to a right inguinal hernia incarceration. During surgery, an
      intestinal granulomatous inflammation was observed adhered to the hernial sac.
      The histopathologic study confirmed the diagnosis of tuberculosis. We present a
      review of the different clinical forms of intestinal tuberculosis and the
      difficulties encountered in the differential diagnosis of such, emphasizing the
      uncommon presentation described in our patient.

PMID- 8984587
TI  - Determination of glucose levels using dried filter paper blood spots: new
      perspective in home monitoring.
AB  - We present a method for the determination of blood glucose using dried filter
      paper blood spots. To validate this method, we compared our results using filter
      paper and simultaneously collected venous blood. We demonstrated that there is a
      linear relationship between the filter paper glucose levels and those determined
      in whole blood (r = 0.98). There was no significant difference between the
      results of the two methods (p > 0.05). This method is a cheap alternative which
      may improve the control of diabetes mellitus, and may also be very useful in the
      diagnosis of postprandial hypoglycemia and other special situations.

PMID- 8984588
TI  - [Ultrasonography: a complement to sialography in recurrent chronic childhood
      parotitis].
AB  - The objective of this research is to compare the ultrasonographic (USG) and
      sialographic contributions for the diagnosis of Recurrent Parotitis in Childhood
      (RPC). Bilateral USG of the parotid gland was performed among 16 children with
      RPC and 16 healthy children. The image of the normal parotid glands was compared
      with the image of the parotid gland with RPC. A pathologic USG pattern for RPC
      was obtained which consisted in a homogeneous, micronodular parenchyme with a
      diffuse increase density, sometimes with multiples hypoechogenous areas, that
      were considered solid hypoechogenous nodules suggesting inflammatory nodes. A
      glandular contour finely granulated was described with normal peri-parotidareas
      and with aponeurotic-muscular planes. Then 16 USG of the parotid gland of the
      children with RPC were compared with 16 Sialography previous obtained. The
      possibilities of diagnosis of the disease with both techniques was not different
      (p > 0.05). When the clinic was correlated with the USG it was possible to obtain
      parameters of severity of the glandular damage and to visualise the degree of
      changes of the parenchyma of each child with RPC. In some cases, bilateral damage
      was observed in children with clinical unilateral symptoms. The USG was performed
      in children in the acute phase of disease, visualising the microabscess in the
      gland and confirming the previous diagnosis. Finally, it was possible to conclude
      the utility of USG in the study of the disease. Being a not invasive exam,
      harmless, unpainfully echography, was easily accepted by the child. Also, we
      obtain information not only about the diagnosis of the disease, but also about
      the severity, prognosis, treatment and follow-up of the infant patients.

PMID- 8984589
TI  - [Salivary calculi. Apropos of 41 cases].
AB  - This retrospective study presents a clinical analysis of 41 patients with
      salivary gland calculi. Epidemiological, clinical, radiological, mineralogical
      and therapeutical aspects are presented and discussed. Surgical treatment is the
      most used but new technics of lithotripsy and/or ultrafine fibroscopy, which are
      more comfortable and less invasive, may reduce the surgical indications.

PMID- 8984591
TI  - [Blade implants: new ideas].
AB  - It is often thought that the insertion of laminar implants is imprecise, poorly
      standardized, and consequently, does not favour integration into the bone. We
      have been able to confirm that laminar implants are integrated into the bone in
      an experimental dog model and in pathology studies. To avoid the inconveniences
      often encountered, we developed a new concept laminar implant. Characteristics of
      the implant Body thickness = 1.2 mm; length = 20 and 16 mm; height of body = 6 or
      8 mm; shaft : 3.25 mm diameter. The most important feature is that the upper part
      of the sheath around the collar does not overrun the upper border of the body by
      more than 1 mm. The total height is thus 7 or 9 mm. Insertion technique Discs are
      mounted on the counter-angle at increasing thicknesses. The third and last disc
      is 1.2 mm thick and has a radius corresponding to the 7 or 9 mm implant. The
      mandibular canal is perfectly protected with this technique. Indications Thin
      crests in the molar region of the mandible. Minimal bone between the crest and
      the mandibular canal. Subsinus implantation.

PMID- 8984590
TI  - [The keratocyst or epidermoid cyst: the current state of understanding apropos of
      a case with intracranial involvement].
AB  - The authors report a case of penetration of an odontogenic keratocyst into the
      skull base. There is significant controversy about what is the optimum surgical
      treatment for the odontogenic keratocyst. Diagnosis, mode of growth and
      recurrence of keratocyst are still a great deal of interest. This paper reports
      the recent advances in the subject.

PMID- 8984592
TI  - [Prosthetic dental rehabilitation on osseointegrated implants placed in
      irradiated mandibular bone. Apropos of 50 implants in 17 patients treated over a
      period of 5 years].
AB  - The authors report on their experience with prosthetic dental rehabilitation of
      17 patients after surgery and radiotherapy for oncologic diseases of the oral
      cavity. 50 implants were inserted either in the mandibular residual bone or in a
      bone graft. These implants were inserted at least 5 months after radiotherapy,
      and functionally loaded at least 5 months after implanting. Depending on the
      degree of edentation, 2 to 6 implants were necessary to allow for a functional
      removable or fixed denture. 2 implants were lost because of lack of
      osseointegration and 10 were lost because of death of 4 patients. The longest
      observation period was 56 months and the mean observation time was 29 months. Not
      any osteoradionecrosis occurred : nevertheless, implantation in irradiated bone
      must remain a carefully planned operation in selected patients with a rigourous
      therapeutic protocol.

PMID- 8984593
TI  - [Selected indications of embolization of vascular malformations of the face.
      Apropos of 2 cases].
AB  - Interventional radiology has dramatically contributed to a better management of
      patients with a facial vascular malformation. Due to the extent of the lesion,
      these patients were formerly difficult to cure, but hyperselective embolisation
      can now overcome these problems with minimal risks. We present our therapeutic
      approach in 2 cases with favorable results and the choice of an embolization
      particle is discussed according to recent datas.

PMID- 8984594
TI  - [Meniscal surgical fixation using arthrotomy: impact on the movement of the
      temporomandibular joint].
AB  - The treatment of severe internal derangement of the temporomandibular joint
      includes, among a number of techniques, the procedure of open surgery to
      reposition the disc. The American Academy of Orofacial and maxillofacial surgery
      has established a guidelines to prescribe the best surgical technique as well as
      criteria to evaluate the post-surgery results. However, little has been done to
      measure the effects of the procedure on the amplitude of movement of the
      temporomandibular joint. The aim of this study was to evaluate the kinematics of
      the TMJ using axiographic registration of the mandibular movements. Twenty-one
      patients were examined 6 months after surgery. In this group of patients there
      was a total representation of 35 joints that had received the surgical procedure.
      The analysis of the results demonstrated the following: - a reduction in the disc
      condylar range of movement, - an increase of angulation in the tracing of the
      disccondyle complete translation, - a change in the shape of the condylar paths.
      The surgical repositionning of the TMJ disc is not a good means to restore the
      normal range of movement and function of the articulation However, it is a
      valuable technique when the patient suffers a sever handicap that has not been
      alleviated by non invasive methods.

PMID- 8984595
TI  - [The contribution of arthroscopic treatment in temporomandibular disk-condyle
      displacements].
AB  - We report a prospective study of thirty four therapeutic temporomandibular
      arthroscopies that were done during a 24 months period for patients with
      debilitating joint disorders (mainly disc displacements with or without
      reduction) who had not responded to no-invasive treatment. The technics used were
      lysis and lavage with prediscal section and retrodiscal coagulation. Analysis of
      the results indicated subjective lessening of pain in 71% of cases, noise in 78%
      (with objective evidence of disappearance of noise in 29%), jaw opening in 94%
      (mean 9.4 mm) and diet in 97% (mean 9.4 mm). In jaw opening, improvement was
      highly significant, compared with the preoperative results, p < 0.01. We conclude
      that temporomandibular arthroscopy is safe and indicated in disc displacements
      and joint luxation if medical treatment has failed.

PMID- 8984596
TI  - [The value of ultrasonographic monitoring in mandibular lengthening using the
      Ilizarov principle. Preliminary results].
AB  - From a review of the literature and a clinical case, we demonstrate the value of
      ultrasonographic monitoring of mandibular distraction according to the Ilizarov's
      protocol. Unlike X rays, sonography offers early and reliable pictures of the
      ossification process. The ultrasonic image matches the histological aspect
      obtained in the course of experiment. A more accurate monitoring of the
      regenerating area is thus made possible.

PMID- 8984597
TI  - 10th Highlights of Gastroenterology in The Netherlands. Proceedings of a
      symposium. Curacao, 5-9 April 1995.

PMID- 8984598
TI  - [Thalassemia today].

PMID- 8984599
TI  - [Osteopenia in beta-thalassemia major].
AB  - Regular blood transfusions in patients with beta-thalassaemia major lead to
      secondary hemochromatosis in the majority of cases. As a consequence of chronic
      iron overload, many endocrinopathies may occur. The most frequent endocrine
      dysfunction is hypogonadotropic hypogonadism, which is mainly responsible for
      osteopenia in as much as 80% of thalassemic patients. The frequencies of other
      endocrine disorders (hypothyroidism, diabetes mellitus and hypoparathyroidism)
      are lower. We investigated 5 female patients aged 22-25 years for endocrine
      dysfunction and bone density. All presented with hypogonadotropic hypogonadism
      and amenorrhea (four primary and one secondary). 4 patients showed absent or
      delayed pubertal development and short stature (below 10th percentile). In all
      five, hypogonadism is the most relevant cause of osteopenia as demonstrated by
      osteodensitometry. Endocrine disorders, especially absent pubertal development,
      should be detected in good time and treated with hormonal replacement.
      Established osteopenia is treated hormonally and with vitamin D3 and calcium.

PMID- 8984600
TI  - [Decongestant nasal spray. Results of a rhinomanometric double-blind study].
AB  - Between november 1993 and july 1995 60 patients with a common cold underwent
      randomized and double-blind testing of 3 commercial nasal sprays-benzydamine,
      xylometazoline combined with the secretolytic S-carboxymethylcysteine, and
      phenylephrine combined with the antihistaminic dimethindene maleate. After prior
      active rhinomanometric measurement of the untreated nose, the test substance was
      applied. The change of nasal patency was registered after 3 and 10 minutes and
      then after 2, 4, 6 and 8 hours. At the end the patient gave a subjective
      evaluation of the used spray. There was no change in nasal obstruction following
      application of NaCl or benzydamine. Xylometazoline/S-carboxymethylcysteine (+87%)
      or phenylephrine/ dimethindene maleate (+113%) augmented nasal patency within
      minutes. Using phenylephrine/dimethindene maleate the effect lasted less than 2
      hours, while after xylometazoline/S-carboxymethylcysteine decongestion lasted
      more than 6 hours. The patients also subjectively reported an increase in nasal
      patency after the use of benzydamine and placebo. But only phenylephrine/
      dimethindene maleate or xylometazoline/S-carboxymethylcysteine were judged good.
      Using benzydamine or phenylephrine + dimethindene maleate, more side-effects
      (mainly dryness and burning) were mentioned. Considering the subjective
      assessment of side-effects and duration of action, as well as objective
      parameters, derivatives of imidazole (oxymetazoline and xylometazoline) are first
      choice in treatment of the common cold.

PMID- 8984601
TI  - [Prostate-specific antigen in the diagnosis of organ-confined treatable prostate
      carcinoma].
AB  - Prostate cancer is now the most common cancer and the second most common cause of
      death from cancer among men. Several studies have shown a frequency of autopsy
      detected cancer of 40% in men over 50 years of age. In contrast, the lifetime
      probability of prostate cancer being diagnosed clinically is only 8%. Thus
      histologically documented prostate cancer only becomes clinically relevant if the
      tumors are > 0.5 cm3 and the life expectancy exceeds 10 years. Therapy with
      curative intention is only possible for organ confined disease. Because disease
      specific survival is about 80-90% after 10 years for conservative treatment of
      organ confined disease, early detection of prostate cancer is useful for patients
      with a life expectancy > 10 years. Organ confined prostate cancer is usually
      asymptomatic. The use of prostate specific antigen (PSA) combined with digital
      rectal examination (DRE) results in a 2-3 fold increase in prostatic carcinoma
      detection rate, especially of organ confined disease, by PSA. In men with a
      minimally elevated PSA-value of 4-10 ng/ml (Hybritech Assays), 25% will have a
      prostatic carcinoma regardless of the finding of the DRE, which would have
      reached clinical significance in the follow-up. The indication for biopsy should
      be established at an early date. There is no support for the common opinion that
      early detection programs detect clinically unimportant cancers. 95% of tumor
      volumes are > 0.5 cm3. Furthermore only 3-5% of subjects show prostate cancer in
      detection programs though 8% will develop clinical symptoms of prostate cancer
      during their lifetime. This difference is a reason for longitudinal programs with
      PSA and DRE control once a year, as proposed by the American Cancer Society and
      the American and Canadian Urological Association, in contrast to other health
      care organizations, which would wait with general screening until data from
      prospective randomized trials with beneficial effects of screening are available.
      To introduce prostate cancer therapy with curative intention for symptomatic
      patients as well, the cancer should be detected below a PSA level of 10 ng/ml.
      Insufficient specificity of PSA (2-4 patients have to undergo biopsies to detect
      one cancer patient) is still an unsolved problem.

PMID- 8984602
TI  - [Rapidly progressive ascites].
AB  - A 50-year-old woman rapidly developed ascites with jaundice and worsening of
      general condition. On admission a nodule of the left breast was noted. Workup
      showed slight anomalies in liver tests and led to the diagnosis of portal
      hypertension, without visible lesion (CT scan, ultrasonography) of the liver. The
      patient suffered severe bleeding caused by esophageal varices necessitating
      urgent sclerotherapy. Several days later, her condition worsened rapidly due to
      acute respiratory distress syndrome followed by irreversible shock.

PMID- 8984603
TI  - [Aortic valve abscess with perforation in the right atrium].

PMID- 8984604
TI  - [Current approach in antithrombotic treatment during coronary interventions:
      specific thrombocyte aggregation inhibitors and direct thrombin antagonists in
      high-risk patients].
AB  - Patients undergoing angioplasty (PTCA) for unstable angina, postinfarction
      angina, or complex coronary lesions represent a high risk group for ischemic
      complications. High dose heparin and aspirin are used routinely to prevent
      thrombotic complications. However, new approaches designed to avoid platelet
      aggregation, including development of specific platelet GP IIb/IIIa receptor
      antagonists and specific thrombin inhibitors, demonstrate a significant reduction
      of thrombotic events following coronary interventions compared to heparin alone.
      Bleeding complications are not increased if conjunctive heparin administration is
      weight-adjusted. Pathophysiology of acute coronary closure, mechanisms of action
      of the new anti-thrombotic drugs, and current and future clinical applications
      are discussed.

PMID- 8984605
TI  - [Autologous blood donation--good clinical practice and good recuperation
      practice].
AB  - Since October 1987, autologous blood donations have been performed in Bern and in
      1994 reached a total of 946, representing 3% of all blood donations. This value
      is lower than the 4.9% for Switzerland as a whole. We report on the motivation
      and reasons of patients in favour of autologous blood donations and compare the
      results of 1989 with 1995. In the 6 years' period, the median patient's age
      increased from 54 to 63 years. The motivation for autologous blood donations
      changed from "routine surgical office" to "doctors". More than 50% of the
      patients mentioned the risk of acquiring an infectious disease, especially HIV,
      as the main reason for autologous blood donations. Labeling, testing or storage
      of autologous blood products of 37 out of 100 patients was incorrect, and in a
      another 20% an enquiry at the donation centres was needed to confirm the required
      quality of the autologous blood products. In 7 cases only one out of several
      blood bags was screened for viral diseases, and in 5 cases, unfortunately, none
      of the autologous blood products were tested for HIV or hepatitis B and C.
      Considering the negative cost-effectiveness of autologous blood transfusion, it
      is strongly recommended that the intrinsically low clinical benefit of autologous
      blood product should not be compromised by lack of good clinical practice and
      good manufacturing practice.

PMID- 8984606
TI  - [Diagnosis of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) is a frequent complication of chronic liver
      disease. The major causes of chronic liver diseases are hepatitis B virus (HBV)
      or hepatitis C virus (HCV) infection, as well as chronic alcohol misuse. The
      clinical presentations of HCC patients are unspecific, with signs and symptoms of
      chronic liver disease. Early diagnosis of HCC in an asymptomatic and potentially
      curable stage is of highest priority. The present strategy for the detection of
      early HCC in patients with chronic liver disease is 6-monthly determination of
      alpha-fetoprotein (AFP) and ultrasound study of the liver. If these are abnormal,
      further diagnostic steps include computer tomography, magnetic resonance
      tomography, lipiodol-angiography and histopathology. By this sequential
      diagnostic strategy it should be possible to identify HCC in patients with
      chronic liver disease at an early and potentially curable stage.

PMID- 8984607
TI  - [Therapy of hepatocellular carcinoma].
AB  - The therapeutic modalities in patients with hepatocellular carcinoma (HCC) depend
      on the number, size and location of the lesions as well as the stage of the
      underlying liver disease and the physical condition of the patient. In patients
      with small and solitary lesions, resection, liver transplantation and in some
      cases percutaneous ethanol injection (PEI) can be curative. In more advanced
      stages of the disease with larger or multiple lesions, PEI and/or transarterial
      chemotherapy with or without embolization (TACE or TAC) can slow the progression
      of the disease. In disseminated disease, a radiotherapeutic approach can be taken
      in selected cases. The therapeutic strategy in patients with HCCs should be
      individualized, frequently involving a combination of therapeutic modalities. In
      contrast to the earlier dismal prognosis, for most HCC patients there is today a
      therapeutic strategy that results in prolongation of life and in some cases even
      cure.

PMID- 8984608
TI  - [HIV infection, tuberculosis and tuberculin test in Switzerland. The Swiss HIV
      Cohort Study].
AB  - BACKGROUND: The usefulness of the tuberculin skin test (TST) for HIV-infected
      subjects may be questioned because false-negative results are increasingly common
      with advanced immune deficiency. The objectives of this research were thus to
      describe the use and the results of TST among patients with HIV infection in
      Switzerland and to measure the usefulness of isoniazid preventive chemotherapy
      and the incidence of tuberculosis (TB) relative to TST and CD4 cell count at the
      time of TST. DESIGN: Prospective multicentric cohort study of HIV infected
      patients; comparison of patients tested and non-tested, and of those with
      positive and negative TST. Multivariate comparison (Cox model) of TB incidence
      taking into account TST results and CD4 cell count at the time of TST. RESULTS:
      Out of 5802 patients followed up in the Swiss HIV cohort study as of September
      1994, 34.6% were tested. Native Swiss were more likely to be tested than patients
      from high TB prevalence countries (36% vs 21% of native Africans). Patients
      registered after 1990 were more often tested than before (50% vs 26%). Of 2010
      tested patients, 6.8% had a > 5 mm induration. African patients were more
      frequently TST positive (26%) than Swiss nationals (6%). Among patients with CD4
      > 500 per mm3 at the time of the test, 16% were TST positive compared to 1% of
      those with CD4 < 200 per mm3. Out of 25 cases of tuberculosis among tested
      patients, 84% (21) occurred among TST-negative patients. Tuberculosis incidence
      among TST-negative patients with CD4 > or = 200 per mm3 at the time of the test
      was 0.3 per person-year. In comparison, the adjusted relative risk of
      tuberculosis among TST-positive patients with CD4 > or = 200 per mm3 was 5.5 (95%
      confidence interval [CI]: 1.2-23.9) and 6.6 (CI: 2.3-19.0) among TST-negative
      patients with CD4 < 200 per mm3. CONCLUSION: Despite its usefulness, TST is often
      performed too late and is therefore difficult to interpret. TST should be done as
      early as possible. TST should be done as early as possible. Among patients with
      CD4 < 200 per mm3, a negative TST should not preclude the use-of preventive
      chemotherapy, particularly in those originally from countries with a high
      incidence of tuberculosis.

PMID- 8984609
TI  - [Replacement of total hip prosthesis--what does the patient expect? Analysis of
      248 aseptic hip revisions].
AB  - Aseptic loosening of prosthesis with consequential revision operations continues
      to be a major problem for both the patients concerned and the medical team. In
      the center of interest stands the magnitude of bone destruction caused by
      loosening effects. A concept designed to avoid uncontrolled progressive loss of
      bone stock is presented. Based on the experience of 248 cases of hip revision
      operations, advice to patients can be given. 2 septic (0.8%) and 6 aseptic (2.4%)
      cases with loosening and re-revision were documented. Statistical analysis of 5
      year survivorship rate according to Kaplan-Meier shows 94.5%, and according to
      Armitage 92.5%. Clinical and radiologic 5-10-year findings in the first 72
      consecutive cases are presented. Routine controls in patients with hip prostheses
      for early detection of bone destruction may help to perform simple and
      prognostically favourable revision operations.

PMID- 8984610
TI  - [Results with a new therapy concept in anal fistula: suture of the anal
      sphincter].
AB  - Eleven patients with suprasphincteric, translevatoric, or high transsphincteric
      fistula and 10 patients with low (transsphincteric or intersphincteric) fistula
      were treated by fistulectomy using sphincterotomy or a transsphincteric approach,
      with primary sphincter reconstruction. After a follow-up of 2-9 months one
      patient had a recurrence and in a further patient the internal anal sphincteric
      suture had become dehiscent, necessitating sphincteroplasty. 20 patients (95%)
      had a perfect anatomic and clinical functional result without recurrence.
      Fistulectomy with primary closure proved to be a safe treatment modality for
      primary and recurrent high and low fistula, with the advantages of rapid wound
      healing and of avoidance of continence disturbance due to sphincter division,
      anal canal deformity, or mucosal flap ectropion.

PMID- 8984611
TI  - [Immunosuppressive treatment of a spontaneous inhibitor hemophilia A using
      cyclophosphamide, vincristine and prednisone following prior Factor VIII
      stimulation].
AB  - A 59-year-old patient who presented with hematuria and recurrent soft tissue
      bleeding was found to have a factor VIII inhibitor level of 52 Bethesda units
      (BU)/ml and acquired hemophilia was diagnosed. After treatment with
      immunoglobulins (0.4 g IgG/kg per day for one week) the factor VIII inhibitor
      titer decreased to 12 BU/ml. Because of another episode of retroperitoneal
      hemorrhage, the patient was put on an immunosuppressive combination therapy which
      was first described by Lian et al. (1988). Our patient was infused with a factor
      VIII concentrate followed by cyclophosphamide, vincristine and prednisone. This
      regimen was repeated every 3-4 weeks. After 6 courses a further decline in the
      factor VIII inhibitor concentration, but no complete eradication of the
      autoantibody, was achieved. The factor VIII inhibitor level has remained at 2.5
      BU/ml for more than 7 weeks without further bleeding episodes. The
      pathophysiology and treatment of acquired hemophilia are discussed.

PMID- 8984613
TI  - Jungle medicine.

PMID- 8984612
TI  - [SMW 100 years ago. William Thomas Green Morton and the discovery of anesthesia].

PMID- 8984614
TI  - Deaths caused by alcohol.

PMID- 8984615
TI  - The man who would conquer malaria.

PMID- 8984616
TI  - "Struck" by fraud?

PMID- 8984617
TI  - Mental health and disability.

PMID- 8984619
TI  - Sex and gender.

PMID- 8984618
TI  - After the genome.

PMID- 8984620
TI  - Sex and gender.

PMID- 8984621
TI  - Ethics of AIDS study.

PMID- 8984622
TI  - Thyroid protection.

PMID- 8984623
TI  - Kessler's legacy: unfinished reform.

PMID- 8984624
TI  - Draft research code raises hackles.

PMID- 8984625
TI  - Korean institute ponders role in global eradication efforts.

PMID- 8984626
TI  - A new embryo zoo.

PMID- 8984627
TI  - Neuroscientists seek answers to brain function and disease. The anatomy of
      learning.

PMID- 8984628
TI  - Neuroscientists seek answers to brain function and disease. Faulty protein linked
      to ALS.

PMID- 8984629
TI  - Expanding the eukaryote's cast of chaperones.

PMID- 8984630
TI  - Nanosecond crystallographic snapshots of protein structural changes.

PMID- 8984631
TI  - Promiscuous chromosomal proteins: complexes about sex.

PMID- 8984632
TI  - A fin-de siecle achievement: charting new waters in vertebrate biology.

PMID- 8984633
TI  - Pharmacia Biotech & Science Prize. 1996 grand prize winner. RNA editing hints of
      a remarkable diversity in gene expression pathways.

PMID- 8984634
TI  - Viewpoint: putting the cell cycle in order.

PMID- 8984635
TI  - Mechanisms of punctuated evolution.

PMID- 8984636
TI  - Dating the cenancester of organisms.

PMID- 8984637
TI  - Dating the cenancester of organisms.

PMID- 8984638
TI  - Gibbons warns of decline in R&D.

PMID- 8984639
TI  - Funding inequality threatens novel bioscience program.

PMID- 8984640
TI  - Fly sex drive traced to fru gene.

PMID- 8984641
TI  - Scientists angle for answers.

PMID- 8984642
TI  - Dissecting how presinilins function--and malfunction.

PMID- 8984643
TI  - Homo erectus in Java: a 250,000-year anachronism.

PMID- 8984644
TI  - Learning rediscovered.

PMID- 8984645
TI  - Crossing the hydrophobic barrier: insertion of membrane proteins.

PMID- 8984647
TI  - DNA looping and lac repressor-CAP interaction.

PMID- 8984646
TI  - Plasticity of a different feather?

PMID- 8984649
TI  - The loss of atmosphere from Mars.

PMID- 8984648
TI  - DNA looping and lac repressor-CAP interaction.

PMID- 8984650
TI  - Alzheimer's precursor protein and the use of bathocuproine for determining
      reduction of copper(II)

PMID- 8984651
TI  - Breakthroughs of the year, 1996.

PMID- 8984652
TI  - New hope in HIV disease.

PMID- 8984653
TI  - Meeting standards.

PMID- 8984654
TI  - Origins researchers win Gore's ear, not pocketbook.

PMID- 8984655
TI  - Fraud and ethics charges hit stroke drug trial.

PMID- 8984656
TI  - Baltimore to head new vaccine panel.

PMID- 8984657
TI  - Genes, junctions, and disease at cell biology meeting.

PMID- 8984658
TI  - Tumor-killer made; how does it work?

PMID- 8984659
TI  - Ironing out the wrinkles in the prion strain problem.

PMID- 8984660
TI  - Fly gene discovery gets at root of branching structures.

PMID- 8984661
TI  - Does Europa's ice hide an ocean?

PMID- 8984662
TI  - Complexities in the treatment of autoimmune disease.

PMID- 8984663
TI  - Consequences of retinal color coding for cortical color decoding.

PMID- 8984664
TI  - Evaluating the evidence for past life on Mars.

PMID- 8984665
TI  - Evaluating the evidence for past life on Mars.

PMID- 8984666
TI  - Evaluating the evidence for past life on Mars.

PMID- 8984667
TI  - [The hematology laboratory in the study of malignant blood diseases.
      Introduction].

PMID- 8984668
TI  - [The examination of peripheral blood and bone marrow in the diagnosis of
      malignant blood diseases].

PMID- 8984669
TI  - [The immunology laboratory in malignant blood diseases].

PMID- 8984671
TI  - [Cell cultures in the study of malignant blood diseases].

PMID- 8984672
TI  - [Applications of fluorescence in situ hybridization in the study of hematologic
      neoplasms].

PMID- 8984670
TI  - [Cytogenetics in the study of malignant blood diseases].

PMID- 8984673
TI  - [Molecular biology in malignant blood diseases. Methodological aspects: Southern
      blotting techniques and the polymerase chain reaction].

PMID- 8984674
TI  - [Molecular biology in malignant blood diseases. Clinical applications. Study of
      immunoglobulin and T-cell receptor genes and molecular analysis of the
      translocations].

PMID- 8984677
TI  - The immune response to infectious diseases of the central nervous system: a
      tenuous balance.
AB  - The outcome of CNS infection is dependent on both the organism and host. Acute
      infections are usually cleared with minimal residua. However, chronic infections
      of the CNS, such as HIV, PML, HSV, polio, Lyme neuroborreliosis, and
      neurosyphilis, are becoming increasingly recognized as a cause of severe
      neurological morbidity, and are poorly understood. We will need to learn more
      about the CNS as an immune compartment to increase our knowledge of these
      infections.

PMID- 8984675
TI  - Experimental immunotherapies for multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central
      nervous system (CNS) principally in young adults. Although its etiology is as yet
      unknown current evidence suggests that tissue damage is mediated by autoimmune T
      cells. The examination of an experimental animal model for MS, experimental
      allergic encephalomyelitis (EAE), has demonstrated that myelin basic protein
      (MBP)- or proteolipid protein (PLP)-specific T cells mediate the destruction of
      CNS myelin. In recent years, elegant studies in EAE have shown that
      encephalitogenic T cells recognize short peptides of MBP or PLP in the context of
      MHC/HLA-class II molecules, express a restricted number of T cell receptor (TCR)
      molecules and secrete interferon-gamma and tumor necrosis factor-alpha/beta.
      Understanding the pathogenetic steps in lesion development at the molecular level
      led to highly specific immunotherapies for EAE targeting each individual
      molecule. It has been the hope of many investigators that immunological events
      resembling those in EAE can be found in patients with MS and that the specific
      immunotherapies effective in EAE could also be applied to MS. However, to date,
      the evidence for a unique immunological abnormality in MS is not strong. Although
      MBP- and PLP-specific T cells with properties similar to those that are
      encephalitogenic in animals can be isolated from patients, they are not specific
      for MS and occur with similar frequency in controls. In addition, the variability
      in specificity and TCR usage has raised questions regarding the relevance of
      these cells in patients. The importance of the T cell responses to myelin
      antigens in MS may not be established until the effects of abrogating their
      activity through specific therapies targeting the trimolecular complex (TMC) have
      been demonstrated. Consequently, attention has begun to focus on modifying the
      biology of the MS lesion rather than targeting the initiating event at the level
      of the TMC, and the success of this approach is reflected by the effect of
      interferon-beta on lesion development in MS. The recent approval for the use of
      interferon-beta for the treatment of relapsing-remitting MS has raised great
      interest in examining novel strategies for immunotherapies in MS. The basic
      concepts as well as the current candidates for such new immunotherapies will be
      outlined in this short review.

PMID- 8984676
TI  - Mechanisms of action of interferon-beta in multiple sclerosis.

PMID- 8984678
TI  - Immune control of the brain.

PMID- 8984679
TI  - Superantigens in demyelinating disease.

PMID- 8984680
TI  - Pathophysiology of the blood-brain barrier.

PMID- 8984681
TI  - Peripheral neuropathy in polyarteritis nodosa.

PMID- 8984682
TI  - Neurological paraneoplastic syndromes.

PMID- 8984685
TI  - [Tumor treatment is a multidisciplinary field].

PMID- 8984684
TI  - [Still only in small steps.. Interview by Klaus Reinhardt].

PMID- 8984686
TI  - [Classification of malignant lymphomas--current status and clinical
      implications].
AB  - New techniques such as cytogenetics, molecular biology and immunology have
      provided new insights into the pathogenesis and development of malignant
      lymphomas. By this way they provided a new basis for a classification of lymphoid
      malignancies which is increasingly oriented on biology and pathogenesis. This
      process resulted in the 'Revised European-American Lymphoma' (R.E.A.L.)
      classification, which was recently proposed by an international group of
      pathologists. This classification comprises a preliminary end point of a
      continuing process which will require a reevaluation and adaptation to new
      knowledge in the future again. In order to facilitate the clinical use of this
      histopathologically and biologically oriented classification, a proposal for a
      clinical grouping was developed, which divides the R.E.A.L. lymphoma subtypes
      into the following categories: I. Indolent lymphomas (low risk group). II.
      Aggressive lymphomas (intermediate risk group). III. Very aggressive lymphomas
      (high risk group). IV. Morbus Hodgkin. This internationally developed consensus
      of a histopathologic classification and a clinical grouping is a substantial step
      forward towards an international cooperation in the management of malignant
      lymphomas. It is background for cooperative studies and justifies the hope that
      further advances will be achieved in the treatment of malignant lymphomas and
      that more effective strategies can be developed in the near future.

PMID- 8984687
TI  - [Hormone therapy of metastasizing breast carcinoma].
AB  - In patients with metastatic breast cancer, cure is almost always an exception,
      irrespective of the therapy given. Thus the preservation of the quality of life
      or palliation in case of symptoms must be the principal goal. Only a small group
      of patients with their tumour showing a highly aggressive behaviour should be
      considered for primary chemotherapy. Aggressive tumour growth is then
      characterized by negative hormonal receptors, short disease-free interval and
      predominant visceral tumour growth. For all other patients there is not enough
      advantage to justify the clearly higher toxicity of a primary chemotherapy. This
      majority of patients with metastatic breast cancer can profit to a higher degree
      from hormonal treatment. Irrespective of the type of the hormonal therapy, the
      response rate is positively correlated with postmenopausal status, high hormonal
      receptor expression, al long disease-free interval, no previous adjuvant therapy
      and higher age. Advantages and problems of the various forms of hormonal
      manipulations are discussed. The recommended sequence of therapy represents only
      a handrail that needs to be adjusted carefully, according to the individual
      situation, the needs and expectations of the patient and in due knowledge of the
      toxicity of each hormonal substance. Combinations of different hormonal agents do
      not yield an additional benefit and should therefore be dropped for a sequential
      approach.

PMID- 8984688
TI  - [Therapy of rectal carcinoma: oncologically adequate surgery is crucial].
AB  - The surgeon plays a major role in rectal cancer treatment concerning local
      recurrence and long-time survival. Thus, the rate of locally recurrent disease
      ranges from 4 to 55%. This state-of-the-art article points out the latest
      findings of surgical therapy, such as the total mesorectal excision, the limits
      of sphincter-preserving resection, the minimally invasive procedures and others,
      and reveals their impact on the patients outcome. Hence, oncologically adequate
      surgery allows to reduce the rate of local recurrence to 5 to 10% and to reach a
      5-year survival rate of 70 to 80%.

PMID- 8984689
TI  - [Questions and answers on adjuvant systemic therapy in breast carcinoma].
AB  - We review controversial issues taken from the vast literature on adjuvant
      treatment of early breast cancer. We conclude that the role of tamoxifen in
      premenopausal women is still controversial and that ovariectomy in this patient
      population cannot be routinely recommended outside clinical trials. The current
      literature certainly supports the use of anthracyclines in adjuvant chemotherapy
      regimens, but we feel that high dose chemotherapy with peripheral blood stem cell
      support should still be restricted to randomized clinical trials. Finally, we
      would like to emphasize that the current standard of adjuvant treatment of early
      breast cancer are prospectively randomized clinical trials which provide a
      stronghold of good patient care and will allow to tackle and answer important
      controversial issues regarding this frequent cancer.

PMID- 8984690
TI  - [Possibilities and prospects in gene therapy in cancer patients].
AB  - The many different oncological concepts of gene therapy can be classified into
      three major groups. These include immunopotentiation, compensation of oncogene
      and tumor suppressor gene alterations, and suicide gene strategies. Gene marker
      studies and the transfer of drug resistance genes to normal cells have also shown
      to be of some importance in oncology. Although there is no clear demonstration of
      the efficacy of gene therapy so far, it will most likely become part of the
      therapeutic armamentarium of oncologists within the next two to three decades.

PMID- 8984691
TI  - [Empirical antimicrobial therapy in neutropenic patients].
AB  - Infectious complications emerge in more than 80% of neutropenic patients after
      intensive antineoplastic therapy. Empirical antimicrobial intervention is
      mandatory, and initial administration of an antipseudomonal betalactam in
      combination with an aminoglycoside represents the most widely applied standard
      regimen. At least in patients with short-term neutropenia, also an initial
      betalactam monotherapy is accepted. Symptoms of skin or venous-catheter-related
      infection should prompt the addition of a glycopeptide, whereas in case of lung
      infiltrates, amphotericin B should be administered at least after 96 h. of
      nonresponse to the antibiotic first-line therapy. In nonresponders with
      persisting fever of unknown origin, carbapenems or fluoroquinolones in
      combination with a glycopeptide might be considered for second-line treatment.
      The supplementation of a recombinant hematopoietic growth factor [G-CSF or GM
      CSF] shows no significant benefit and should be restricted to controlled clinical
      studies. In case of good clinical response, the established antimicrobial
      treatment regimen should be continued for at least seven days in persistently
      neutropenic patients.

PMID- 8984683
TI  - Autoimmune responses in peripheral nerve.

PMID- 8984692
TI  - [Current status of the clinical application of hematopoietic growth factors in
      oncology].
AB  - With the identification and recombinant production of the hematopoietic growth
      factors, these cytokines have been evaluated in the treatment of primary bone
      marrow failure states and after myelosuppressive chemotherapy or radiotherapy. A
      lot of clinical trials with hematopoietic factors have been performed in patients
      with haematologic and oncologic diseases within the last decade. Granulocyte
      colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating
      factor [GM-CSF], interleukin-3, interleukin-2, erythropoietin and in phase I/II
      trials thrombopoietin [TPO] are available for the clinical use. At the present,
      there is a broad use of growth factors. Most studies have been done with G-CSF
      and GM-CSF, their beneficial effects are proven regarding improvement of
      hematopoietic recovery after chemotherapy. This results in a marked reduction of
      infectious risks and a shortening of drug- and radiation-induced
      myelosuppression. CSFs are most important in mobilizing peripheral blood
      progenitor cells [PBPC] and have allowed high dose therapy to be given to
      patients who would not have been able to undergo conventional bone marrow
      transplantation. However, an improved outcome and improved survival rates with
      standard chemotherapy protocols couldn't be documented by studies up to now, even
      though higher chemotherapy doses are possible by the use of hematopoietic
      factors.

PMID- 8984694
TI  - Interactions between opportunistic micro-organisms and HIV in the lung.

PMID- 8984693
TI  - Functional antagonism: tolerance produced by inhaled beta 2 agonists.

PMID- 8984695
TI  - Carcinoma of the lung: warts and all.

PMID- 8984696
TI  - Steroids, surfactant and lung disease.

PMID- 8984697
TI  - Respiratory dreams and nightmares.

PMID- 8984698
TI  - Presence of human papillomavirus DNA and abnormal p53 protein accumulation in
      lung carcinoma.
AB  - BACKGROUND: In some carcinomas inactivation of the tumour suppressor gene product
      p53, either by point mutation or indirectly by the human papillomavirus (HPV),
      has been suggested as two alternative routes to malignant transformation. To test
      this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ
      hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA,
      and the results were compared with p53 protein immunohistochemical analysis.
      METHODS: The presence of HPV DNA in lung carcinoma was detected by nucleic acid
      in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using
      nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis
      was performed on all cases showing positive HPV DNA labelling by in situ
      hybridisation and in an additional 13 negative cases. Abnormal nuclear
      accumulation of the p53 protein was revealed by immunohistochemistry using the
      avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53
      antibody and a monoclonal mutation-specific Pab 240 p53 antibody. RESULTS: HPV
      DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these
      cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53
      protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were
      HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the
      mutation-specific antibody Pab 240. There was an obvious inverse relationship
      between the presence of papilloma viral DNA and abnormal p53 protein
      accumulation. CONCLUSIONS: p53 plays an important part in the development of lung
      carcinomas and, in some cases, HPV may contribute to it by binding and
      inactivating the p53 protein.

PMID- 8984699
TI  - Prognosis in lung cancer: physicians' opinions compared with outcome and a
      predictive model.
AB  - BACKGROUND: Although the study of prognostic factors in small cell lung cancer
      has reached the stage where they are used to guide treatment, fewer data are
      available for non-small cell lung cancer. Although correct management decisions
      in non-small cell lung cancer depend upon a prognostic assessment by the
      supervising doctor, there has never been any measurement of the accuracy of
      physicians' assessments. METHODS: A group of consecutive patients with non-small
      cell lung cancer was studied and the predictions of their physicians as to how
      long they would survive (in months) was compared with their actual survival. A
      prognostic index was also developed using features recorded at the patients'
      initial presentation. RESULTS: Two hundred and seven consecutive patients
      diagnosed and managed as non-small cell lung cancer, who did not receive curative
      treatment for their condition, were studied. Of the 196 patients whose date of
      death was known, physicians correctly predicted, to within one month, the
      survival of only 19 patients (10%). However, almost 59% of patients (115/196) had
      their survival predicted to within three months and 71% (139/196) to within four
      months of their actual survival. Using Cox's regression model, the sex of the
      patient, the activity score, the presence of malaise, hoarseness and distant
      metastases at presentation, and lymphocyte count, serum albumin, sodium and
      alkaline phosphatase levels were all identified as useful prognostic factors.
      Three groups of patients, distinct in terms of their survival, were identified by
      the use of these items. When the prediction of survival made by the physician was
      included as a prognostic factor in the original model, it was shown to
      differentiate further between the group with a poor prognosis and the other two
      groups in terms of survival. CONCLUSIONS: Physicians were highly specific in
      identifying patients who would live less than three months. However, they had a
      tendency to overestimate survival in these patients, failing to identify almost
      half the patients who actually died within this time. Both the physicians and the
      prognostic factor model gave similar performances in that they were more
      successful in identifying patients who had a short time to survive than those who
      had a moderate or good prognosis. Physicians appear to use information not
      identified in the prognostic factor analysis to reach their conclusions.

PMID- 8984700
TI  - Delays in the diagnosis and surgical treatment of lung cancer.
AB  - BACKGROUND: Patients admitted for resection of lung tumours frequently experience
      lengthy delays in diagnosis and preoperative investigations. This study was
      conducted to quantify this delay between presentation and definitive treatment
      and to assess the factors responsible for such a delay. METHODS: All patients
      undergoing lung resection for a tumour at a single surgical unit in 1993 were
      studied. The date of each consultation, investigation, and referral was
      identified, and the extent of any delay determined. RESULTS: The mean total delay
      from presentation to operation was 109 days. Within this period an average of one
      month occurred before referral to a respiratory specialist who then spent two
      months investigating the patient. After referral to a surgeon, surgery took place
      within a mean interval of 24 days. CONCLUSIONS: These delays to definitive
      treatment appear unacceptable. Points at which the efficiency of the diagnostic
      process could be improved are discussed. The length of delay did not correlate
      with tumour stage in this study.

PMID- 8984701
TI  - Measurement of pulmonary status and surfactant protein levels during
      dexamethasone treatment of neonatal respiratory distress syndrome.
AB  - BACKGROUND: Early postnatal use of dexamethasone in infants with respiratory
      distress syndrome (RDS) has been shown effectively to improve pulmonary status
      and to allow early weaning off mechanical ventilation. However, the mechanisms to
      explain the beneficial effects of dexamethasone in ventilatory dependent preterm
      infants remain unclear. METHODS: A double blind, placebo controlled study was
      performed to determine the change in pulmonary ventilation of premature infants
      with RDS as a result of dexamethasone treatment, and to evaluate the effect of
      dexamethasone on the levels of surfactant-associated proteins A (SP-A) and D (SP
      D) in the tracheal fluid from 34 premature infants with RDS and 29 control
      subjects. RESULTS: Dexamethasone treatment decreased fractional inspired oxygen
      concentration (FIO2), arterial carbon dioxide tension (PCO2), mean airway
      pressure (MAP), and facilitated successful weaning from mechanical ventilation.
      SP-A concentrations in the tracheal aspirates were increased at days 7 and 14,
      and SP-D concentrations were increased during the period from days 3 to 14 in the
      dexamethasone treated group compared with the control group. However, albumin
      levels in the tracheal aspirate samples were decreased after dexamethasone
      treatment over the period from days 3 to 14. There was an inverse correlation
      between PCO2 values and SP-A concentrations. CONCLUSIONS: These results suggest
      that early use of dexamethasone can improve pulmonary status and also increase SP
      A and SP-D levels in the tracheal fluid in premature infants with RDS.

PMID- 8984702
TI  - Chronic sputum production: correlations between clinical features and findings on
      high resolution computed tomographic scanning of the chest.
AB  - BACKGROUND: There are few published data on the correlation between the clinical
      findings in subjects with chronic sputum production and the appearances on high
      resolution computed tomographic (HRCT) scans of the chest. METHODS: HRCT scanning
      of the chest was performed on 40 subjects with chronic sputum production. Three
      readers independently reported the scans for the presence or absence of
      bronchiectasis and the extent of bronchiectasis on the basis of the percentage of
      involved bronchi in each lobe. Relationships were sought between these findings
      and the clinical history, physical examination, and laboratory investigations.
      RESULTS: HRCT scanning showed that 27 subjects had bronchiectasis. Of the
      clinical features only the continual production of purulent sputum and childhood
      pertussis were associated with bronchiectasis. There was a positive correlation
      between the extent of bronchiectasis and dyspnoea, and a negative correlation
      with forced expiratory volume in one second but not with forced vital capacity.
      CONCLUSIONS: These results indicate that, in subjects with chronic sputum
      production, only a few clinical features show any correlation with the presence
      or extent of bronchiectasis as visualised on HRCT scans.

PMID- 8984703
TI  - Effect of prostaglandin E2 on eicosanoid release by human bronchial biopsy
      specimens from normal and inflamed mucosa.
AB  - BACKGROUND: Eicosanoids such as prostaglandin E2 (PGE2), thromboxane A2 (TXA2),
      and peptidoleukotrienes (pLT) are known to be biologically highly active lipid
      mediators, especially in human lung epithelium. PGE2 is thought to have mostly
      bronchoprotective effects, whereas pLT and TXA2 are bronchoconstrictive. This
      study was undertaken to assess the release and interaction of eicosanoids in
      human bronchial biopsy specimens of normal and inflamed mucosa. METHODS:
      Bronchial biopsy specimens were obtained from 16 patients, seven controls without
      signs of inflammation and nine patients with severe inflammatory processes in the
      epithelium. The release of pLT, TXA2 (measured as TXB2), and PGE2 was
      investigated using a "functional in vitro test" and the addition of several
      stimuli. RESULTS: Specimens incubated with arachidonic acid released higher
      amounts of pLT, TXB2, and PGE2 than unstimulated specimens. Preincubation with
      PGE2 revealed significant inhibition of arachidonic acid-induced release of pLT
      and TXB2 (> 50%). The inhibitory effect was higher in normal than in inflamed
      epithelium. CONCLUSIONS: Exogenous PGE2 has inhibitory effects on the release of
      pLT and TXB2 in human bronchial biopsy specimens. This finding could explain the
      bronchoprotective effect of inhaled PGE2 in normal subjects and asthmatic
      subjects as direct eicosanoid interactions. It also supports the concept of PGE2
      as a bronchoprotective endogenous substance. The complex effects of PGE2 as a
      modulating mediator in inflammation may be worth investigating.

PMID- 8984704
TI  - Accuracy of recording of deaths from asthma in the UK: the false negative rate.
AB  - BACKGROUND: A study was carried out to determine the extent to which asthma
      deaths are wrongly attributed to another cause on UK death certificates. METHODS:
      Deaths from all causes occurring anywhere in the UK were identified amongst 2382
      subjects aged 16-64 years within three years of discharge following hospital
      treatment for asthma (ICD9 493) in hospitals in the South East Thames region. The
      deaths were reviewed by an expert panel to assess the proportion of asthma deaths
      identified by the panel which were attributed to another cause of death on the
      death certificate (false negatives). RESULTS: Eighty five deaths from all causes
      were identified in a mean follow up period of two years and three months. In 61
      cases (72%) there was sufficient information for the expert panel to be confident
      about the cause of death. The panel identified 22 deaths from asthma, four of
      which were certified as non-asthma deaths (two as deaths from chronic obstructive
      pulmonary disease (COPD) and two as deaths from cardiovascular disease). The
      proportion of false negative death certificates was four of 22 (18%, 95%
      confidence interval (CI) 5 to 40). CONCLUSIONS: There is evidence that asthma
      deaths in the UK are wrongly certified as deaths from both chronic obstructive
      pulmonary disease and diseases of the cardiovascular system.

PMID- 8984705
TI  - Comparison of bronchoscopic diagnostic techniques with histological findings in
      brain dead organ donors without suspected pneumonia.
AB  - BACKGROUND: The techniques for recognising pneumonia in mechanically ventilated
      patients were evaluated as no "gold standard" is available to establish the
      diagnosis in these patients. METHODS: A prospective study was performed on nine
      brain dead organ donors not suspected of having pneumonia to assess the
      specificity of bacteriological results from different samples by comparing them
      with the histological findings from an open pulmonary biopsy specimen taken
      immediately after death through a mini-thoracotomy. RESULTS: Seven of the nine
      organ donors without clinical evidence of pulmonary infection and not on
      antibiotic therapy showed histological features of bronchopneumonia. There was no
      association between the histological findings and quantitative cultures of the
      lung biopsy specimen. CONCLUSIONS: Histological evidence of pneumonia was common
      in this group of ventilated patients who had no clinical signs of the disease.

PMID- 8984706
TI  - Lack of skin test reactivity to common mycobacterial antigens in human
      immunodeficiency virus infected individuals with high CD4 counts.
AB  - BACKGROUND: T cell response to mycobacterial antigens may be directed against
      those antigens common to all mycobacteria (group i), those restricted to slow
      (group ii) or fast growers (group iii), or those which are species- or subspecies
      specific (group iv). These responses were assessed by skin testing patients
      infected with the human immunodeficiency virus (HIV) and healthy controls with
      reagents derived from different strains of mycobacteria. METHODS: Skin test
      responses to new tuberculins prepared from Mycobacterium tuberculosis, M avium
      serotypes 4 and 8, and either M intracellulare or M flavescens antigens were
      evaluated prospectively in 51 HIV infected patients and 67 healthy controls.
      RESULTS: Assessment of induration at 72 hours showed absence of skin test
      response to common mycobacterial antigens in all 27 HIV positive patients with
      CD4 counts of > or = 400/mm3 (range 400-1594, median 540) compared with 27%
      reactivity in controls; complete anergy was demonstrated in 24 patients with CD4
      counts of < 400/mm3. By contrast, no difference in species or subspecies-specific
      responses was found between healthy controls and HIV positive patients with CD4
      counts of > or = 400/mm3. CONCLUSIONS: Subsets of CD4+ T helper cells are
      instrumental in determining the balance between cell-mediated and humoral
      immunity. One T helper subset (TH1) produces cytokines that increase cellular
      immunity and is stimulated by group i common mycobacterial antigens. Lack of this
      response, but preservation of responses to species-specific antigens while CD4
      counts are near normal, may indicate an early failing of TH1 immunity and explain
      the increased susceptibility of HIV positive patients to mycobacterial infection
      early on in the evolution of their HIV infection.

PMID- 8984707
TI  - Quality of life in adults with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis is an inherited condition with a high mortality and
      morbidity. The aims of this study were to assess quality of life in a population
      of adults with cystic fibrosis, to compare quality of life with published scores
      from a healthy population and other patient groups, and to examine the relation
      between quality of life and other measured clinical variables. METHODS: Patients
      over 16 years of age attending an adult cystic fibrosis outpatient clinic were
      surveyed at a time when they were clinically stable. A self-complete
      questionnaire was administered which comprised the Nottingham Health Profile
      (NHP) together with six additional questions related to cystic fibrosis. RESULTS:
      Completed questionnaires were obtained from 240 subjects (100 women) of median
      age 26 years (range 16-56). Mean (SD) forced expiratory volume in one second
      (FEV1) was 49 (26)% predicted, forced vital capacity (FVC) was 68 (26)%
      predicted, and the FEV1:FVC ratio was 59 (16)%. In this cross sectional study
      different patterns of perceived quality of life were seen in men and women. In
      part 1 of the NHP there was an age related trend compared with norms in men, with
      more distress/disability in the dimensions of emotion, sleep, and social
      isolation in the older age groups. In women there was no age related trend in the
      degree of distress/disability compared with norms. The mean score was different
      from norms in the dimensions of pain, emotion and sleep. For the patients with
      cystic fibrosis as a whole the scores in part 1 were comparable with published
      scores of patients with minor non-acute conditions. Scores in part 2 of the NHP
      for men were different from norms in six of the seven areas of daily living (all
      except home life). For women the scores were different from norms in the areas of
      looking after the home, social life, hobbies, and holidays. There were
      correlations between several of the quality of life dimensions and other measured
      variables such as FEV1, breathlessness score, and the time spent on home
      treatment. CONCLUSIONS: Men and women with cystic fibrosis have different
      patterns of perceived quality of life, and there is an age related trend of
      perceived quality of life in men in some dimensions. Quality of life scores in
      this group, as assessed by the NHP, are similar to those reported in subjects
      with minor non-acute conditions.

PMID- 8984708
TI  - Adrenal suppression with inhaled budesonide and fluticasone propionate given by
      large volume spacer to asthmatic children.
AB  - BACKGROUND: The aim of this study was to compare the systemic bioactivity of
      inhaled budesonide (B) and fluticasone propionate (F), each given by large volume
      spacer, on a microgram equivalent basis in asthmatic children. METHODS: Ten
      stable asthmatic children of mean age 11 years and forced expiratory volume in
      one second (FEV1) 81.6% predicted, who were receiving treatment with < or = 400
      micrograms/day of inhaled corticosteroid, were studied in a placebo controlled
      single blind (investigator blind) randomised crossover design comparing single
      doses of inhaled budesonide and fluticasone propionate 400 micrograms, 800
      micrograms, and 1250 micrograms. Doses were given at 20.00 hours with mouth
      rinsing and an overnight 12 hour urine sample was collected for estimation of
      free cortisol and creatinine excretion. RESULTS: The results of overnight 12 hour
      urinary cortisol output (nmol/12 hours) showed suppression with all doses of
      fluticasone propionate (as geometric means): F400 micrograms (11.99), F800
      micrograms (6.49), F1250 micrograms (7.00) compared with placebo (24.43), whereas
      budesonide caused no suppression at any dose. A comparison of the drugs showed
      that there were differences at 800 micrograms and 1250 micrograms levels for
      urinary cortisol: B800 micrograms versus F800 micrograms (2.65-fold, 95% CI 1.26
      to 5.58), B1250 micrograms versus F1250 micrograms (2.94-fold, 95% CI 1.67 to
      5.15). The results for the cortisol/creatinine ratio were similar to that of
      urinary cortisol, with fluticasone causing suppression at all doses and with
      differences between the drugs at 800 micrograms and 1250 micrograms. CONCLUSIONS:
      Single doses of inhaled fluticasone produce greater systemic bioactivity than
      budesonide when given by large volume spacer on a microgram equivalent basis in
      asthmatic children. The systemic bioactivity of fluticasone, like budesonide, is
      due mainly to lung bioavailability.

PMID- 8984709
TI  - Seasonality of tuberculosis: the reverse of other respiratory diseases in the UK.
AB  - BACKGROUND: In Western societies there is a winter peak in mortality, largely
      accounted for by respiratory and cardiovascular deaths. In view of the known
      seasonal variation in vitamin D, and of the postulated link between tuberculosis
      and vitamin D deficiency, a study was undertaken to examine whether the
      presentation of tuberculosis had the same seasonal rhythm as other pulmonary
      infections. METHODS: Using cosinor analysis the presence or absence of
      seasonality was determined for 57,313 tuberculosis notifications for England and
      Wales. OPCS data in four weekly notifications over a 10 year period (1983-92)
      were examined as two quinquential sets (1983-7 and 1988-92). These were compared
      with two groups of acute respiratory illness: 138,992 notifications to OPCS of
      pneumonia deaths for 1988-92 and all admissions to Scottish hospitals with
      respiratory disease (252,163 cases) during 1980-4. RESULTS: Analysis of
      notifications of tuberculosis revealed a summer peak with an amplitude of 10%.
      This pattern differs markedly from other respiratory disorders in which a winter
      peak and summer trough is observed. CONCLUSIONS: The unusual seasonality of
      tuberculosis is currently unexplained. One possibility is that low post-winter
      trough levels of vitamin D (which are known to affect macrophage function and
      cell mediated immunity) might result in impaired cellular immunity leading, after
      a latent period, to reactivation of dormant mycobacterial infection.

PMID- 8984710
TI  - Occupational and chronic obstructive pulmonary disease (COPD)

PMID- 8984711
TI  - Function at the junction: dynamic interactions between lung cells and
      extracellular matrix.
AB  - Recent advances are elucidating the mechanisms by which cells communicate with
      the surrounding matrix. Cells have specific receptors for matrix proteins. A
      number of intracellular molecules with signalling functions aggregate at
      specialised focal adhesion points and facilitate transfer of information both
      into and out of cells. The importance of these signaling processes to cell
      biology makes it likely that manipulation of these processes will allow
      innovative therapeutic approaches to lung disease.

PMID- 8984712
TI  - "Crack lung" caused by an impure preparation.
AB  - Pulmonary complications of crack cocaine have been reported mainly from American
      centres. Crack usage is now on the increase in the UK. Three cases of "crack
      lung" are reported in patients who acquired the drug from the same source. The
      pulmonary syndrome they developed was due to an impure form of crack.

PMID- 8984713
TI  - Ecstasy induced pneumomediastinum.
AB  - Two cases are reported of pneumomediastinum induced by the use of Ecstasy, a semi
      synthetic hallucinogenic compound related to amphetamine and mescaline which has
      become established as a recreational drug in the UK since the late 1980s. Both
      cases recovered without incident, but it is important that the possible
      complications of this drug be publicised so that at risk subjects can be
      diagnosed early and managed appropriately.

PMID- 8984714
TI  - Commentary. Ecstasy and crack cocaine.

PMID- 8984715
TI  - Expandable metal stents for non-malignant bronchial obstruction.
AB  - An expandable metal stent was inserted to relieve bronchial obstruction following
      lobectomy for localised squamous carcinoma which had not been relieved by
      bronchoplasty with a Goretex flap. This resulted in substantial improvement in
      lung function and exercise tolerance for nine months, following which severe
      inflammation around the stents required residual pneumonectomy.

PMID- 8984716
TI  - Functional upper airways obstruction: two patients with persistent symptoms.
AB  - Functional upper airways obstruction is caused by vocal cord dysfunction and
      classically occurs in paroxysms closely resembling acute asthmatic attacks. We
      present two cases in which the symptoms and signs of the vocal cord dysfunction
      demonstrate very little variability with time. We suggest that as part of this
      disorder, a syndrome of chronic unremitting symptoms may occur.

PMID- 8984718
TI  - Who should look after asthma?

PMID- 8984717
TI  - Community-acquired Chlamydia pneumoniae pneumonia.

PMID- 8984719
TI  - Fibreoptic bronchoscopy for diagnosis of isolated tuberculous mediastinal
      lymphadenopathy.

PMID- 8984720
TI  - Measuring systemic effects of inhaled beclomethasone.

PMID- 8984722
TI  - [Avian influenza a potential threat for poultry farming].

PMID- 8984721
TI  - [Verocytotoxin-producing Escherichia coli O157 in Dutch veal calves and beef
      cattle].
AB  - In 1994 (August-September) and in 1995 (July-October) faeces of Dutch veal calves
      and adult cattle was examined for the presence of verocytotoxin-producing
      Escherichia coli O157 (O157 VTEC). The samples were collected at slaughterhouses.
      In 1994, O157 VTEC were isolated from three (0.9%) of 365 fecal samples of veal
      calves. Faeces of adult cattle was not collected. In 1995, O157 VTEC were
      isolated from one (0.5%) of 18.3 fecal samples of veal calves and from 30 (11.1%)
      of 270 fecal samples of adult cattle. In 1994, the organisms were isolated by
      selective plating onto both sorbitol MacConkey agar (SMAC) and SMAC containing
      tellurite and cefixime (TC-SMAC) following selective enrichment in modified
      trypton soya broth with acriflavin (mTSB + a). In 1995, the samples were enriched
      in modified E. coli broth with novobiocin (mEC + n), and in addition to directly
      plating onto TC-SMAC the enriched cultures were plated after incorporation of an
      immunomagnetic separation step of E. coli O157. All 30 strains isolated from
      adult cattle were isolated with the immunomagnetic separation procedure. Four of
      the 30 samples were determined positive also by directly plating onto TC-SMAC.
      The sample from the veal calve was determined positive only by directly plating
      onto TC-SMAC. Plating onto SMAC resulted only in negative results.
      Characterization of the O157 VTEC isolates showed similarities between isolates
      of humans and cattle. Additional experiments need to be done concerning this
      aspect. From this study it appeared that also Dutch cattle are a reservoir of
      O157 VTEC.

PMID- 8984723
TI  - [Workshop Vaccinology Rhone Merieux. Annual revaccination under discussion].

PMID- 8984724
TI  - [Working on a moral viewpoint].

PMID- 8984725
TI  - [Cat-scratch disease in humans and the cat's role. Causative agents finally
      isolated].

PMID- 8984726
TI  - Proceedings of the 4th International Congress of Therapeutic Drug Monitoring and
      Clinical Toxicology. Vienna, Austria, September 4-8, 1995.

PMID- 8984727
TI  - Gene expression: increasing evidence for a transcriptosome.

PMID- 8984728
TI  - Puzzling out the genetics of mammalian sex determination.

PMID- 8984729
TI  - Rapid sequencing protocol using microconcentrators.

PMID- 8984730
TI  - Coding in noncoding frames.

PMID- 8984731
TI  - Control of messenger RNA stability in higher eukaryotes.
AB  - The mRNA decay rate (half-life) is a major determinant of mRNA abundance in
      organisms from bacteria to mammals. mRNA levels can fluctuate many-fold following
      a change in mRNA half-life, without any change in transcription, and these
      fluctuations affect how a cell grows, differentiates and responds to its
      environment. The half-lives of many mRNAs vary tenfold or more in response to
      cytokines, hormones, starvation, hypoxia, or viral infection. Three major
      questions regarding mRNA stability are currently being addressed. What sequences
      in mRNAs determine half-lives? What enzymes degrade mRNAs? What (trans-acting)
      factors regulate mRNA stability and how do they function? This review focuses on
      RNA-binding or regulatory proteins and on candidate messenger ribonucleases
      (mRNases).

PMID- 8984732
TI  - Olfaction in Drosophila: from odor to behavior.
AB  - Odors elicit a variety of behavioral responses from Drosophila via a relatively
      simple, but sensitive, olfactory system. An increasing number of mutants have
      been found to be defective in olfactory function. Genetic and molecular analyses
      of the Drosophila olfactory system have identified some of its molecular
      components, and have revealed some principles of its function and organization.

PMID- 8984733
TI  - Creating conditional mutations in mammals.
AB  - For many years geneticists have relied on conditional activation to study the
      roles of cytolytic or cytostatic proteins in lower eukaryotes or to elucidate the
      epistatic relationships of proteins in a signaling pathway. Regardless of their
      merits, conditional mutants have only been available to mammalian geneticists
      within the past few years. Moreover, the approaches that exist are still limited
      to a subset of signaling molecules and are not reliable for in vivo studies. Now,
      added to the biologist's toolbox is a versatile new approach based on chemically
      induced dimerization that should allow for the reversible regulation of proteins
      at the cell surface, intracellularly, in the nucleus and in vivo.

PMID- 8984734
TI  - Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: do the genes
      explain the diseases?
AB  - Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy are three
      distinct human syndromes associated with sensitivity to ultraviolet radiation. We
      review evidence that these syndromes overlap with each other and arise from
      mutations in genes involved in nucleotide-excision repair and RNA transcription.
      Attempts have been made to explain the syndromes in terms of defects in repair
      and transcription. These two biochemical pathways do not easily account for all
      the features of the syndromes. Therefore, we propose a third pathway, in which
      the syndromes are due, in part, to defects in a demethylation mechanism involving
      the excision of methylated cytosine. Perturbation of demethylation could affect
      the developmentally regulated expression of some genes.

PMID- 8984735
TI  - Complications and implications of linear bacterial chromosomes.
AB  - The emergence of linear bacterial chromosomes has overthrown the dogma of
      universal circularity of the bacterial chromosomes, and posed mechanistic and
      evolutionary implications not previously anticipated.

PMID- 8984737
TI  - TiPS on identity.

PMID- 8984736
TI  - The cancers of man and woman.

PMID- 8984738
TI  - The TiPS/TINS lecture. Catecholamines: from gene regulation to neuropsychiatric
      disorders.
AB  - In addition to their ability to change the electrical properties of neurones,
      evidence suggests that neurotransmitters are able to alter the cell's metabolism.
      Transmitter phenotype is labile and expression might be regulated, during
      development, by the cellular environment of neurones. The study of a key enzyme
      in the synthesis of catecholamines, tyrosine hydroxylase (TH), has provided clues
      about these adaptive responses. This enzyme has a large molecular diversity,
      resulting from the differential splicing of its mRNA, which is tissue-specific
      and might result in long-term changes in activity of the enzyme and, therefore,
      in the availability of neurotransmitter at various synapses. The presence of
      different DNA sequences at the TH locus confers susceptibility to various
      disorders of the brain, including manic-depressive illness and schizophrenia.
      Indeed, an association between a rare variant allele of the gene encoding TH and
      the occurrence of schizophrenia has been found in several populations. New
      techniques being developed to treat diseases such as Parkinson's disease involve
      various gene therapies, including a method of transferring genes directly into
      nerve cells using an adenovirus-based system.

PMID- 8984739
TI  - The ligand binding site of the angiotensin AT1 receptor.
AB  - The angiotensin AT1 receptor mediates numerous physiological actions of the
      octapeptide hormone, angiotensin II, in its cardiovascular and other target
      tissues. The binding of angiotensin II to the AT1 receptor is dependent on both
      intramembrane and extracellular regions of the receptor molecule. Non-peptide
      antagonists that block angiotensin binding and action interact exclusively with
      residues located within the intramembrane binding pocket of the AT1 receptor.
      However, peptide ligands also interact with extracellular residues to form
      additional bonds that stabilize their binding to the receptor. Here, Laszlo
      Hunyady, Tamas Balla and Kevin Catt describe how these and other studies have
      shown that interaction of ligands with residues in the intramembrane binding
      pocket is the conserved mechanism required for agonist activation of G protein
      coupled receptors.

PMID- 8984740
TI  - Excitatory actions of adenosine on ventricular automaticity.
AB  - Due to its negative chronotropic and inotropic effects, adenosine has to date
      been considered as a cardiodepressant agent. However, adenosine increases
      ventricular automaticity. This review by Jesus Hernandez and Alexandre Ribeiro
      discusses the experimental and clinical evidence for the excitatory effects of
      adenosine on ventricular automaticity, as well as the possible mechanisms
      involved in the ventricular dysrhythmias that occur during the diagnostic and
      therapeutic use of adenosine.

PMID- 8984741
TI  - Heterodimerization between mineralocorticoid and glucocorticoid receptors
      increases the functional diversity of corticosteroid action.
AB  - Gene regulation by steroids is mediated by the binding of the endogenous or
      pharmacological ligand to the corresponding nuclear receptor. Ligand-activated
      steroid receptors usually regulate the expression of responsive genes by binding
      to common response elements on DNA as homodimers. However, recent findings
      indicate that mineralocorticoid and glucocorticoid receptors are able to interact
      by forming heterodimers. In tissues coexpressing both of these corticosteroid
      receptors, heterodimerization between them may be a hitherto unrecognized
      modality for the transcriptional regulation of corticosteroid-responsive genes.
      In this review, Thorsten Trapp and Florian Holsboer discuss the potential impact
      of this heterodimerization on corticosteriod physiology and pharmacology.

PMID- 8984742
TI  - Prozac: panacea or puzzle?
AB  - Selective 5-HT (serotonin) reuptake inhibitors (SSRIs) lack many of the adverse
      side-effects of older antidepressants. One of these compounds, fluoxetine
      (Prozac), has acquired manifest public awareness that is not evident with other
      SSRIs. Here, Clare Stanford compares the basic pharmacology of SSRIs to determine
      whether fluoxetine has any atypical features, and thus provide scientific
      justification for the attention focused on this compound. Ironically, fluoxetine
      might be distinctive in that it is the least selective SSRI and has marked
      effects on catecholamine function in the brain.

PMID- 8984743
TI  - Lewy-body dementia and responsiveness to cholinesterase inhibitors: a paradigm
      for heterogeneity of Alzheimer's disease?
AB  - The concept of heterogeneity of Alzheimer's disease is based on molecular,
      neuropathological, clinical and neuropsychological features, and also supported
      by the observation that Alzheimer's patients differ in their response to
      pharmacological interventions. Recent investigations evaluating the therapeutic
      potential of cholinesterase inhibitors have disclosed the existence of at least
      two subsets of patients with dementia, defined as 'responders' and
      'nonresponders' to this therapy. In this article, Paolo Liberini and colleagues
      suggest that the cluster of responders to the cholinesterase inhibitors might
      include a significant number of subjects with a rather selective dysfunction of
      the cholinergic system, as in the case of Lewy-body dementia. A neuropathological
      demonstration of this correlation should open up new therapeutic perspectives.

PMID- 8984744
TI  - Urinary bladder function and drug development.
AB  - Disorders of the bladder are extremely common and are becoming more so in an
      ageing population. Recently, our understanding of lower urinary tract physiology
      and pathology has also increased. Here, Douglas Ferguson and Nim Christopher
      summarize this new knowledge of lower urinary tract function, the changes in
      innervation that occur with age and the common disease states, and discuss how it
      is being used to develop new drug treatments for bladder disorders.

PMID- 8984745
TI  - Corticotrophin-releasing factor receptors: from molecular biology to drug design.
AB  - Corticotrophin-releasing factor (CRF) acts within both the brain and the
      periphery to coordinate the overall response of the body to stress. The
      involvement of the CRF systems in a variety of both CNS and peripheral disease
      states has stimulated great interest in this peptide as a potential site of
      therapeutic intervention. The recent cloning of multiple CRF receptor subtypes
      has precipitated a new era in CRF research that has allowed precise molecular,
      pharmacological and anatomical examination of mammalian CRF receptors. In this
      article, Derek Chalmers and colleagues highlight the major differences between
      the two classes of CRF receptors, CRF1 and CRF2, and a functionally related CRF
      binding protein, and discuss the relevance of these sites to the ongoing
      development of CRF-based therapeutics.

PMID- 8984746
TI  - [Food and secondary prevention of ischemic heart disease].

PMID- 8984747
TI  - [Rational thoughts without randomized trials].

PMID- 8984748
TI  - [Adverse effects of selective serotonin uptake inhibitors].

PMID- 8984749
TI  - [Significance of food for patients with ischemic heart disease].

PMID- 8984750
TI  - [Recommendations for treatment of paracetamol poisoning. Danish Medical Society,
      Study of the Liver].
AB  - Based on recent reports concerning the efficacy of N-acetylcysteine (NAC) in
      paracetamol (acetaminophen) poisoning, guidelines for treatment and control of
      these patients are reviewed by a study group under the Danish Association for the
      Study of the Liver. It is recommended that NAC-treatment is initiated immediately
      after referral and continued for 36 hours in all cases. Further NAC-treatment
      should not be discontinued before a decrease in INR has been observed.

PMID- 8984751
TI  - [High triglyceride, low HDL-cholesterol and risk of coronary heart disease].
AB  - Hypercholesterolaemia is a strong risk factor of coronary artery disease (CAD).
      The importance of high triglyceride and low HDL cholesterol in predicting risk of
      CAD is less well-established. This review presents data showing that high
      triglyceride and low HDL cholesterol are important risk factors of CAD and
      suggests that combined lipid profiles of triglyceride, HDL cholesterol, and total
      cholesterol provide more information about risk of CAD than total cholesterol
      alone. High triglyceride and low HDL cholesterol is the characteristic
      dyslipidaemia seen in subjects with insulin resistance, a basic abnormality in
      glucose- and insulin metabolism. Since insulin resistance and raised triglyceride
      and decreased HDL cholesterol can be identified in children of patients with
      NIDDM, essential hypertension, and CAD, we suggest that efforts to prevent CAD
      should include interventions against all these associated abnormalities in
      glucose-, insulin-, and lipid metabolism and not only high cholesterol.

PMID- 8984752
TI  - [Obese individuals underestimate their food intake--which food groups are under
      reported?].
AB  - The purpose of the study was to examine the distribution of macronutrient density
      patterns in relation to obesity. This was done in a sample of 323 Danish men and
      women aged 35-65 years, selected randomly from a larger population sample of
      adult Danes. Dietary reporting bias of energy and protein intake, in relation to
      body fat percentage, was assessed by comparing intake data from a diet history
      interview with data estimated from PABA-validated 24-hour nitrogen excretion and
      estimated 24-hour energy expenditure. The results of the study showed that degree
      of obesity was positively associated with protein underreporting of total energy
      and protein, whereas compared with total energy reported, protein was
      overreported by the obese subjects. These associations were evident despite
      control for gender, age and smoking (p = 0.0003). In conclusion, errors in
      dietary reporting of protein seem to occur disproportionately with respect to
      total energy, suggesting a differential reporting pattern of different
      foodstuffs. Although, on average, all subjects over-reported energy percent from
      protein, over-reporting was most common in obese. It may therefore be speculated
      that snack type foods are preferentially forgotten when dietary omission occurs
      in obese individuals. The results of the present study seem in agreement with the
      general assumption that obese subjects tend to specifically under-report fat and
      sugar-rich foods, rather than generally under-report their total intake. These
      results may have wide implications for the interpretation of studies of diet and
      comorbidities to obesity.

PMID- 8984753
TI  - [Albuminuria and glycemic control. The significance for mortality in non-insulin
      dependent diabetes mellitus].
AB  - The impact of microalbuminuria and macroalbuminuria on mortality was evaluated
      prospectively in 328 Caucasian patients with non-insulin-dependent diabetes
      mellitus (NIDDM) followed for five years. One hundred and ninety-one patients
      with normoalbuminuria (albumin excretion rate (AER) < 30 mg/24 h), 86 patients
      with microalbuminuria (AER 30-299 mg/24 h), and 51 patients with macroalbuminuria
      (AER > or = 300 mg/24 h) all less than 66 years old at start of the study were
      followed from 1987 until death or until 1 January 1993. Eight percent of patients
      with normoalbuminuria, 20% of patients with microalbuminuria, and 35% of patients
      with macroalbuminuria had died, predominantly from cardiovascular disease.
      Significant predictors of all-cause mortality included preexisting coronary heart
      disease, AER, HbA1c level and age. Significant predictors of cardiovascular
      mortality included preexisting coronary heart disease, macroalbuminuria, HbA1c
      level and systolic blood pressure. Abnormally elevated urinary albumin excretion
      and poor glycaemic control indicate a substantially increased all-cause, mainly
      cardiovascular, mortality risk in NIDDM patients.

PMID- 8984756
TI  - [Adverse effects of selective serotonin uptake inhibitors. Hyponatremia caused by
      Schwartz-Bartter syndrome].
AB  - This report describes three cases of hyponatraemia/syndrome of inappropriate
      secretion of antidiuretic hormone. The cases are most likely caused by
      treatment/intoxication with three different selective serotonin reuptake
      inhibitors: Fluoxetine, paroxetine and citalopram. All three patients were
      elderly women (75-83 years). Serum sodium values returned to normal or near
      normal after discontinuation of the drug and concomitant fluid restriction.
      Hyponatraemia has previously been described as an adverse effect to fluoxetine
      and paroxetine, but not to citalopram.

PMID- 8984755
TI  - [Anderson-Hynes pyeloplasty in hydronephrosis].
AB  - The purpose of the study was to evaluate pyeloplasty a.m. Anderson-Hynes in the
      treatment of hydronephrosis in a large series of patients. In 175 patients,
      consecutively operated for ureteropelvic junction obstruction, we found 24 (14%)
      with minor postoperative complications, mostly urinary tract infection. Six
      patients (3%) were reoperated because of continued pain and obstructed drainage
      postoperatively. There was a small, but statistically significant increase in
      renal functional share on the operated side. We found a highly significant
      correlation between postoperative changes in total GFR and single kidney GFR on
      the operated side, which suggests a real improvement in renal function, rather
      than a simple reallocation of function between the two kidneys. We conclude that
      newer treatment modalities known as "minimally invasive surgery" must give
      comparably good results in order to be an acceptable alternative to traditional
      dismembered pyeloplasty.

PMID- 8984754
TI  - [Treatment of acute lateral ankle ligament ruptures. A prospective 9-13-year
      follow-up study of three different therapies in 79 patients].
AB  - In a prospective study of 79 patients with arthrographically verified acute
      ruptured lateral ankle ligaments we have evaluated the long-term results of three
      different treatments: operation and walking-cast, walking-cast alone and elastic
      bandage. The average follow-up period was 11 (9-13) years, and 32 parameters
      concerning interview, clinical and radiographic examinations were statistically
      analysed. The three kinds of treatment were found to be equal, since only one
      parameter showed significant difference at a 5% level using Fisher's exact and
      the Mann-Whitney test, and no difference by using the Kruskal-Wallis test for
      homogeneity. Residual disabilities and late complications, such as instability,
      pain on activity, and the number of secondary ligament reconstructions and
      talocrural arthroses were low. It was concluded that nonoperative treatment
      provided adequate results even after a decade.

PMID- 8984757
TI  - [Risk of venous thromboembolism during postmenopausal hormone therapy].

PMID- 8984758
TI  - [The most rapid steroid].

PMID- 8984759
TI  - [Vaccination against influenza of the elderly population of Copenhagen].

PMID- 8984760
TI  - [Serious drug interaction between clozapine-Leponex and fluvoxamine-Fevarin].
AB  - A 67 year-old woman in steady-state treatment with clozapine 150 mg/24 h was co
      medicated with 100 mg/24 h of fluvoxamine. During the next months the patient
      suffered from nausea and occasionally vomited, but these symptoms were ascribed
      to fluvoxamine, and as she mentally improved, both treatments were continued. Two
      months after the start of fluvoxamine her serum clozapine concentration was 7570
      nmol/l or 7.5 fold higher than before fluvoxamine was added. The woman was
      admitted to hospital, suffering from abdominal pain, dehydration and fever (38.5
      degrees C). Serum creatinine concentration was increased, but normalized during
      hydration. After 18 days care the woman felt well and was discharged from
      hospital. The case report shows that certain combinations of selective serotonin
      reuptake inhibitors and neuroleptic drugs should either be avoided or the serum
      concentrations of the drugs closely followed.

PMID- 8984761
TI  - [Serotonin syndrome and malignant neuroleptic syndrome. A review based on the
      material from the National Board of Adverse Drug Reactions].
AB  - The report describes four cases of serotonergic hyperstimulation classified as
      Serotonin Syndrome (SS) and 13 cases of supposed Neuroleptic Malignant Syndrome
      (NMS), all reported to the National Board of Adverse Drug Reactions. Diagnostic
      criteria, pathogenesis and some suspected risk factors are discussed. All
      patients with a diagnosis of "SS" were treated with more than one psychoactive
      drug, whereas five out of 13 NMS patients were treated with only one drug which
      could be suspected to be involved in the pathogenesis of the syndrome. Lithium
      seemed to be involved in three out of four SS cases and in one out of 13 cases of
      NMS. The syndrome occurred from less than an hour to several weeks after adding
      another drug to the patient's treatment. None of the cases of serotonergic
      hyperstimulation were severe enough to correspond to NMS and all patients
      recovered without sequelae, whereas at least three NMS patients died.

PMID- 8984762
TI  - [Why is it necessary to study the thyroid gland?].
AB  - Pathophysiological and clinical aspects of the thyroid gland include after many
      decades of intensive studies many yet unresolved problems. The relationship with
      the gastrointestinal system (iodine accumulation in the stomach and salivary
      glands), the function of thyroxine as a prohormone (in particular the regulation
      of the activity of tissues deiodinases, the action of triiodothyronine similar to
      that of steroid hormones, a mixture of protein anabolic and protein catabolic
      reactions to thyroid hormones, peculiar immune features of the thyroid gland
      (presence of immunogenic hyperfunctional and hypofunctional syndrome), sharing of
      common antigens by the thyroid gland and orbital tissues, new findings on
      mutations of TSH receptors in the thyroid gland, biphasic dependence of the
      thyroid gland on iodine - all these problems call for further research. Mutation
      of the TSH receptor can lead to hypothyroidism (resistance to TSH) and to
      multinodular goitre. The gene for the iodine transporter in the thyroid gland
      (Na(+)I symport) was cloned. The thyroid gland is related to malignant free
      radicals: this is suggested also by the raised thyroxine level in rats after
      methylene blue administration. The increase is recorded in intact as well as
      carbimazole medicated animals. All this indicates that the thyroid gland must
      remain in the foreground of research and clinical work: 4% of the Czech
      population suffer from some thyroid disorder.

PMID- 8984763
TI  - [History of the anatomy and surgery of the thyroid gland].
AB  - The submitted historically oriented paper reviews anatomical and surgical
      prerequisites for the development of thyroid surgery. Operations which up to the
      middle of the last century were associated with an extremely high lethality and
      were considered heroic and unjustified, changed due to new findings and
      procedures into standard operations performed in some thyroid diseases. Despite
      this, indications for operation and views on some surgical procedures are even in
      contemporary medicine highly controversial.

PMID- 8984764
TI  - [The calcium tolerance test in thyrotoxicosis, Hashimoto's thyroiditis and after
      total thyroidectomy].
AB  - Basic indicators of calcium and bone metabolism and the calcium tolerance test
      were investigated in patients with untreated hyperthyroidism, Hashimoto's
      thyroiditis, after total thyroidectomy and in controls. In florid hyperthyroidism
      elevated values of indicators of bone new formation (osteocalcin and bone
      fraction of alkaline phosphatases) and of bone resorption (urinary pyridinoline
      and deoxypyridinoline) were found and a protracted return of the serum calcium
      level to baseline values (during the 120th minute after completed infusion
      containing calcium). The calcitonin serum levels were significantly reduced after
      completion of the infusion up to the 120th minute. These results suggest a
      reduced calcitonin activity in hyperthyroidism, caused probably by exhaustion of
      C cells during the prolonged tendency of hypercalcaemia associated with untreated
      hyperthyroidism. In patients with autoimmune Hashimoto's thyroiditis no
      significant deviations in basal indicators of the calcium and bone metabolism
      were found nor deviations of the serum calcium and calcitonin levels during the
      calcium tolerance test. After total thyroidectomy the basal values of
      calcitoninaemia are significantly reduced and during the calcium tolerance test
      the elevated serum calcium level persists from the end of the calcium containing
      infusion up to the 120th minute. The calcitonin values are at all time intervals
      significantly low or cannot be detected (during the 120th and 240th minute).
      Changes of the serum calcium and calcitonin level are due to the surgical removal
      of the calcitonin source, thyroid C cells. The investigation confirmed the
      impaired calcium and bone metabolism and impaired calcium tolerance test in
      hyperthyroidism and in particular after total thyroidectomy. Reduced calcitonin
      values in these patients can act as a factor promoting the development of
      osteoporosis.

PMID- 8984765
TI  - [The effect of gender on prevalence and survival in thyroid carcinoma].
AB  - Based on their own experience with a large group of patients with thyroid
      cancers, the authors confirm the higher prevalence of differentiated thyroid
      cancers both papillary and follicular (1 : 3,5) in females, while the differences
      in anaplastic and medullary cancers are much less prominent. Survival of females
      in univariate studies is much higher in both papillary and follicular cancers
      compared to males, in multivariate studies these differences lose their
      significance and only in papillary cancers under the age of 40 years at diagnosis
      and in a subgroup of papillofollicular cancers the differences retain their
      significance. The authors therefore deduce that differences found in univariate
      studies are significantly influenced by other factors such as age at the
      diagnosis and the spread of disease at the diagnosis.

PMID- 8984766
TI  - [Thyroid gland function in women with breast carcinoma].
AB  - Data in the literature concerning thyroid disease in women after treatment of
      breast cancer differ. The authors examined therefore the thyroid function
      (thyroid stimulating hormone, thyroxine, triiodothyronine, antibodies against
      thyroid peroxidase and against thyroglobulin) in a random sample of 76 women
      after ablation of the breast on account of carcinoma. A deviation in some of the
      investigated indicators was found in 46,7% of the examined women. A total of
      10,5% women had an elevated level of thyroid stimulating hormone, in 18,4% both
      antibodies were positive, in another 11,8% antibodies against thyroglobulin only
      were positive and in 9,2% antibodies against thyroid peroxidase were positive. In
      none of the women the thyroxine level was beyond the physiological, i.e. normal
      range, the triiodothyronine level was elevated in 5,2%. Newly diagnosed
      subclinical hypothyroidism in 10,5% of the group supports the hypothesis of a
      more frequent thyroid abnormality in women treated on account of breast cancer.
      The cause and sequelae of this finding will be investigated.

PMID- 8984767
TI  - [Hormone suppression therapy in benign nodular goiter].
AB  - Nodular goitre was detected in as many as 21 - 27% of the adult population in a
      non-endemic area. The most frequent therapeutic procedure is suppressive
      treatment with thyroxine. The author analyzes the results of prospective
      randomized, placebo controlled studies, which focused attention on the
      effectiveness of suppressive treatment. In the majority an inadequate effect was
      recorded. In the conclusion the author suggests an algorithm of suppressive
      treatment of nodular goitre and conditions after goitrectomy on account of
      nodular goitre.

PMID- 8984768
TI  - [Organic chlorinated pollutants and the thyroid gland].
AB  - This review presents the definition of main groups of organic chlorinated
      pollutants (polychlorinated biphenyls, dibenzodioxines, dibenzofurans,
      hexachlorobenzene, hexachlorocyclohexane, DDT etc.). Moreover, the similarity of
      their effects with those of steroid and thyroid hormones either via
      steroid/thyroid receptor or via specific Ah-receptor is described. Special
      attention is paid to their effects on the thyroid gland in experimental
      conditions as well as on professionally and nonprofessionally exposed population.
      Finally, own preliminary data are presented which were obtained by the
      examination of 249 employees of the factory Chemko producing polychlorinated
      biphenyls in 1955-85 as compared with control groups of 218 adults from Moldava,
      Trebisov and Kosice and 278 women from Orava. In women from Chemko the frequency
      of thyroid volumes (by ultrasound) over 22,1 ml was 40/202, while that from
      Moldava was 16/170 (p < 0.001). In the employees of Chemko also significantly
      higher frequency of thyroid antibodies anti-thyroperoxidase, anti-thyroglobulin
      and anti-TST-receptor was found.

PMID- 8984769
TI  - [Epitestosterone as an endogenous antiandrogen in men].
AB  - The authors assessed in the plasma of 156 boys and men aged 6 - 65 years and in
      prostatic tissues of 15 men aged 55 - 82 years epitestosterone, C19-steroid with
      anti-androgenic properties. It was revealed that during the prepubertal period
      the epitestosterone level is higher than that of testosterone, in adult age the
      epitestosterone is about ten times lower than the testosterone concentration. In
      tissue of hyperplastic prostates the epitestosterone level is comparable with the
      androstendione level; it is about twice as high as the testosterone level and
      approximately half as high as the dihydrotestosterone level. Thus at least during
      the prepubertal period in boys and in the androgen-dependent prostate tissue a
      more significant participation of epitestosterone in the regulation of androgen
      dependent processes must be taken into consideration.

PMID- 8984770
TI  - [Endocrinopathy in the differential diagnosis of chronic fatigue syndrome].
AB  - Fatigue is a frequent and sometimes dominant symptom of some endocrinopathies. It
      may be associated with other symptoms which are included among the criteria of
      the chronic fatigue syndrome. These units are not always quite distinct and
      frequently endocrine diseases and chronic fatigue syndrome (CFS) overlap. From
      this ensue differential diagnostic problems and ideas on possible causal
      relations. The authors concentrate in articular on autoimmune endocrinopathies
      and the polyglandular autoimmune syndrome (APS) with emphasis on the necessity of
      an accurate endocrinological diagnosis, where is some patients with suspected CFS
      a defined endocrinopathy was revealed. Attention will be also paid to recent
      views on the possible participation of disorders of the hypothalamus-pituitary
      adrenal axis in the etiopathogenesis of CFS where endocrine and immune regulation
      overlap and condition each other.

PMID- 8984771
TI  - [Laboratory monitoring of therapy in Addison's disease].
AB  - Views on the usefulness of monitoring of substitution therapy in Addison's
      disease by hormonal laboratory indicators are controversial. The authors analysed
      the problem therefore in a group of 20 of their own patients. It was revealed
      that the adequacy of substitution of the cortisol deficiency can be very readily
      evaluated by diurnal profiles of cortisolaemia. The values of plasma ACTH
      provided less information, but were not unreliable. Assessment of free urinary
      cortisol did not prove useful. The adequacy of substitution of aldosterone
      deficiency reflected sensitively the plasma renin activity. CONCLUSIONS:
      monitoring by hormonal indicators is useful, basic means are the diurnal profile
      of cortisolaemia and the plasma renin activity.

PMID- 8984772
TI  - [Indications for only pancreatic transplantation in the treatment of diabetes].
AB  - As the safety of simultaneous transplantation of the kidney and pancreas
      worldwide as well as in this country is increasing, transplantation of the
      pancreas only in the treatment of diabetes is becoming a more real issue.
      Reflections pro and con are even more important as transplantation of the
      pancreas is not a life saving operation. Limiting factors are nephrotoxicity of
      cyclosporin and the hitherto not negligible morbidity after transplantation.
      Problems of indication involve evaluation of co-existing diabetic nephropathy and
      the objective evaluation of causes of neuroglycopenia. Transplantation of the
      pancreas alone may be indicated in type 1 diabetics who suffer from life
      threatening hypoglycaemia, not caused by external factors. The prerequisite is
      adequate renal function.

PMID- 8984773
TI  - [Personal experience with the diagnosis of organic hyperinsulinism].
AB  - The diagnosis of organic hyperinsulinism was established in 47 patients based on
      the typical clinical symptomatology supported by laboratory evidence of
      hypoglycaemia and raised serum insulin concentrations. For the diagnosis of the
      disease the test of controlled fasting is suited best. During this test and after
      its termination the blood sugar level (in mmol/l), serum insulin (in mU/l) and
      their ratio (insulin/blood sugar) are assessed. In all patients the test had to
      be discontinued because clinical manifestations of hypoglycaemia developed which
      are typical for organic hyperinsulinism. Other methods, incl, examination by
      means of an isoglycemic clamp or insulin receptors are not specific and cannot be
      used for diagnosis. As to imaging (localisation) methods in the examined group
      the lowest yield was obtained by computed tomography (positive only in one
      patient), better results were obtained by sonography (21%) and angiography resp,
      (45%). When methods were combined an insulinoma was detected in 55% patients
      while on operation it was found in 82% patients. The authors' experience provides
      evidence that for the diagnosis of organic hyperinsulinism a decisive role is
      played by the clinical symptomatology supplemented by laboratory evidence of
      hypoglycaemia and possibly by a raised serum insulin concentration.

PMID- 8984774
TI  - [Comparison of insulin loss in treatment of diabetics using the classical syringe
      or the insulin pen (Novopen II)].
AB  - The aim of the study was to investigate changes in insulin wastage when
      transferring patients from vial insulin to Actraphane HM Penfills and NovoPen II.
      Twenty four diabetic patients, were treated with Actraphane HM 40 IU/ml vial for
      3 months, then transferred to Actraphane HM Penfill and NovoPen II for further 3
      months. Wastage 1 (difference between insulin consumption and the total
      prescribed dose) was higher in vials than in Penfills (268.7 +/- 69.4 IU/3
      months/patients vs. -7.6 +/- 30.2 IU/3 months/patient, p < 0.001 mean +/- SEM).
      Wastage 2 (insulin remaining in the container when discharged) was higher in the
      Penfills than in vials (214.1 +/- 22.04 IU/3 months/patient vs 45.2 +/- 11.2 IU/3
      months/patient). Total wastage was 313.9 +/- 67.8 IU/3 months/patient (3.96
      IU/day/patient) when using vials and 206.5 +/- 31.2 IU/3 months/patient (2.52
      IU/day/patient) when using Penfills (NS). Higher wastage in vials may relate to a
      larger volume used for "airshot", and to a larger imprecision in the measured and
      injected dose when using vials. The latter may also be reflected in a
      significantly higher average incidence of weighted hypogiycemias in the vial
      period (15 +/- 4.28/3 months/patient) compared to the Penfill period (5.1 +/-
      1.2/3 months/patient, p < 0.01). Total wastage was seen to be 29% smaller by
      using NovoPen II and therefore saving of insulin seems to be possible
      (approximately 1.44 IU/day/patient).

PMID- 8984775
TI  - [Personal experience with the Mono type of insulin--clinical study].
AB  - A multicentric study was conducted in March to September 1995 to test the
      effectiveness and tolerance of a new insulin series. A total of 281 diabetics
      above 15 years of age were followed up, 144 men and 137 women, mean age 63 years
      with a duration of diabetes from 0.5 to 51 years, without serious organ
      complications and capable to recognise symptoms of hypoglycaemia. During the
      investigation a total of five examinations of the investigated parameters were
      made. The authors revealed a statistically insignificant decline of body weight,
      blood sugar level on fasting and HbA1c and a significant drop of the postprandial
      blood sugar level. The BP reading and urinary findings were unaltered. The
      authors found a significant drop of the daily insulin dose in MONO N, D and ID
      and an insignificant rise of the daily dose in MONO SD. The investigation
      provided evidence of a satisfactory effectiveness and tolerance of the new
      insulin series. In MONO N, D and ID there was also a decline in the total
      consumption.

PMID- 8984776
TI  - [Is the aldosterone-renin ratio useful in screening for primary aldosteronism?].
AB  - Despite improving laboratory and imaging methods the diagnosis of primary
      aldosteronism still remains a problem. One of the reasons is inadequate
      sensitivity of classical screening of this secondary arterial hypertension by
      hypokalemia. In the submitted paper the authors review data from the literature
      on more sensitive screening by means of the aldosterone-renin ratio. Its
      inclusion among basic examinations in patients with arterial hypertension seems
      fully justified.

PMID- 8984777
TI  - [The clinical aspects of the aftermath of the accident (based on data from the
      Military Medical Academy)].
AB  - The results of medical examinations of the persons taking part in elimination of
      consequences of Chernobyl's disaster obtained by the specialists of Military
      medical academy allowed to verify the conception of damage action of radiation
      and nonradiation complex of injury factors, to estimate well-information of stale
      and new biological indicators of radiation dose, to plan the ways of rescuers
      rehabilitation during stationary, polyclinic and sanatorium stages of treatment.

PMID- 8984778
TI  - [The effect of the factors of a radiation and nonradiation nature on the health
      of the garrison population stationed in a radioactively contaminated area].

PMID- 8984779
TI  - [The hygienic aspects of supporting the safe activities of living for servicemen
      and their family members in a radioactively contaminated area].

PMID- 8984780
TI  - [The prevention and pharmacological correction of body functional disorders from
      exposure to the extreme factors of large-scale radiation accidents].
AB  - The experience of Chernobyl's disaster response showed the necessity of
      adaptation of troops radiative protection medical system to the conditions of
      peacetime. The article describes the tests working out the optimal use scheme of
      time-table medical means of protection under conditions of large-scale radiative
      accidents. The state of neuropsychic activity, cardiovascular, respiratory,
      hemopoietic, immune and other body systems have been studied, perspective ways of
      drug application as means of body resistance increase under such conditions have
      been estimated.

PMID- 8984781
TI  - [The basic trends in improving the dispensary care for servicemen subjected to
      irradiation as a result of radiation accidents].

PMID- 8984782
TI  - [The experience of the medical service of the Armed Forces in the cleanup of the
      aftereffects of the accident at the Chernobyl Atomic Electric Power Station].
AB  - The article analyzes ten-years experience (1986-1996) of the Armed Forces medical
      service participation in elimination of consequences of Chernobyl's disaster. The
      system of medical supply created soon after disaster (management and interaction,
      forces and means, peculiarities of sanitary-hygienic, antiepidemic, treatment-and
      prophylactic supply) has been described in brief, its positive sides and main
      deficiencies and also the ways of there elimination, the place of military
      medical service in modern state system of disaster medical supply have been
      discussed. The results of prolonged dynamic observation of rescuers by the All
      Army medical-and-dosimetric register materials, the main directions, results and
      prospects of scientific study about problems of radiative disaster have been
      analyzed.

PMID- 8984783
TI  - [The health indices of those working in the cleanup during accident recovery
      operations].
AB  - Having analyzed the data base of All-Army register contained information about
      35,970 rescuers it was determined that 45.5% of them during works in dangerous
      radiative conditions complained of the health change for the worse characterized
      by the state of irritation of mucous membrane of superior respiratory and
      gastrointestinal tracts. The direct correlation between value of irradiation dose
      and frequency of complaints, and also degree of lowering of there physical
      performance have been defined.

PMID- 8984784
TI  - [The All-Russia Disaster Medical Service in the organization of the cleanup of
      the aftermath of radiation accidents].

PMID- 8984785
TI  - [The psychological sequelae of the accident].
AB  - The psychological status of rescuers of consequences of Chernobyl's disaster,
      having planned stationary examination and treatment of common somatic diseases,
      has been examined. The age of men represented the study group was 35-54 years
      old. The next methodics have been used: questionnaire MMPI (adapted by L.
      N.Sobchik), the method of colour choice (adapted version of Liusher's test) and
      questionnaire of Spilberger-Khanin. The results of medical-psychological
      examination showed the development in rescuers of common dysadaptation and stress
      state, characterized by depressive-hypochondriac state with high anxiety. The
      course of psychotherapeutic activities made possible to improve essentially the
      psychological status of the patients.

PMID- 8984786
TI  - [Low doses of irradiation and psychoemotional stress].

PMID- 8984787
TI  - [The effect of protein deficiency on the clinical course of pneumonia and the
      immunological indices of young people].

PMID- 8984788
TI  - [Rheumatism and aspects of the chronicity of the rheumatic process].

PMID- 8984789
TI  - [Transesophageal electrostimulation of the heart in the diagnosis of sinus node
      dysfunction].

PMID- 8984790
TI  - [Outstanding historian of Russian military medicine (on the 90th anniversary of
      the birth of S. A. Semeka)].

PMID- 8984791
TI  - [The 125th anniversary of Yaroslavl Military Hospital].

PMID- 8984792
TI  - [Interrelationship between pro-oxidant and immunomodulating properties of vitamin
      D].
AB  - It was shown in experiments on mice that 1.25 (OH)2D3 ingested per os in dose 100
      ng during 5 days caused the great increasing of lipid peroxidation (LP) in
      peritoneal macrophages and spleen cells. The evidence of LP induction is the
      production of TBA-positive substances in these cells. Linear negative dependence
      was found between increasing of LP and functional activity of lymphocytes which
      was evidenced by blast transformation of lymphocytes under effect of concanavalin
      or mitogen of laconose. Linear positive correlation was shown between level of LP
      and function of macrophages.

PMID- 8984793
TI  - [Vitamin and mineral status of the population living in the Sverdlovsk region].
AB  - It was found that low nutritional status for vitamin C, B2, beta-carotene,
      selenium and calcium are most prominent nutritional problem for population of
      Sverdlovskaja region of Russia. Level of calcium in serum was low in 50% of
      examined population. The results suggest the necessity of dietary intake and food
      contamination assessments for this population.

PMID- 8984794
TI  - [Chemicals in agriculture and problems of ecologically clean and biologically
      full-value food products].
AB  - Modern state of agricultural chemistry in Russia and over the world are
      discussed. At present time there are no the other ways to provide the provision
      security and independence of country than using of fertilizers and other
      agricultural chemicals. It is underlined that using agricultural chemicals such
      as fertilizers, pesticides, growth regulators and others on basis of scientific
      regulations and ensuring of absolute control of their application does not make
      worse the quality and biological value of food. Prohibition or abrupt reduction
      of application of agrochemicals will come undoubtedly to definitive destruction
      of self food provision in country. The evidence of such conclusion in
      unprecedented low harvest of cereals in Russia in 1995.

PMID- 8984796
TI  - [A new therapeutic-prophylactic product with an immunomodulating additive].

PMID- 8984795
TI  - [Selenium status of healthy children under 1 year of age dependent on the type of
      feeding].
AB  - Selenium status was studied in 70 healthy children under 1 year of age being on
      breastfeeding or bottle feeding. Selenium status was determined by analysis of
      selenium in baby's hairs and nails. Selenium was also analyzed in breast milk in
      course of the lactation and in breast milk substitutes. The selenium status was
      better in breastfed children than in bottle fed ones. The most high level of
      selenium was found in breast milk in first month of lactation. Selenium status of
      bottle fed children was depended on selenium level in milk substitutes. It is
      necessary further investigations on selenium status of children under 1 year age
      to elaborate and suggest the standard level of selenium contents in milk
      substitutes.

PMID- 8984797
TI  - [Selenium status of different population groups of the Bashkortostan Republic].
AB  - Human selenium status of various groups of Bashkortostan population was studied.
      Mean serum selenium levels for healthy adults of Ufa, Salavat, Sterlitamak were
      98 +/- 11 mg/l (n = 92), 96 +/- 10 mg/l (n = 35), 103 +/- 11 mg/l (n = 20). Serum
      selenium concentrations for rural populations were found to be smaller: Tolbasy -
      84 +/- 13 mg/l (n = 10), Chishmy - 87 +/- 10 mg/l (n = 11), Ufa suburb - 86 +/- 9
      mg/l (n = 10). 7-10 years old children of Ufa demonstrated 83 +/- 11 mg Se/l
      serum and 11-14 years old group - 95 +/- 11 mg/l. Pregnant women serum selenium
      happened to decrease by 20-30% at the end of the second part of gestation and
      reached the values of 55-70 mg/l in small settlements. Thus epidemiological data
      show the possibility of potential selenium deficiency risk for rural pregnant
      women and 7-10 years old children in Bashkortostan.

PMID- 8984798
TI  - [Comparative evaluation of hypolipidemic effects of omega-3 polyunsaturated acids
      and lipostabil].
AB  - Comparative effect of eiconol (resource of omega-3 PUFA) and lipostabil on lipid,
      biochemical, hemostatic parameters in blood and activity of lipolytic enzymes in
      thrombocytes and monocytes was studied in 18 clinic patients with ischemic heart
      disease fed antiatherosclerotic diet during 2 weeks. On basis of these parameters
      was concluded that eiconol and lipostabil showed the strong hypolipidemic effect.
      Fibrinolytic effect showed only eiconol. The results showed that hypolipidemic
      and fibrinolytic actions more strong at treatment by eiconol.

PMID- 8984799
TI  - [A study of lipid peroxidation in patients with chronic gastritis during
      administration of a food additive monosodium glutamate].
AB  - The levels of diene conjugates (DC) and TBA-reactive substances (TBA-RS) were
      studied in serum blood of patients with gastritis before and after including in
      diet of monosodium glutamate (MSG). For investigation 15 patients were selected
      who had unacid or subacid signs determined by histamine test. It was shown that
      levels of DC and TBA-RS were increased in serum of patients. MSG increased the
      gastric secretion in patients but had no effect of levels of DC and TBA-RS in
      serum.

PMID- 8984800
TI  - [Effectiveness of certification].

PMID- 8984801
TI  - [Instrumental methods and express analyzers for measuring composition and quality
      of milk and dairy products].

PMID- 8984802
TI  - [Specific features of studies of glucose in biological fluids (review)].
AB  - The review is devoted to the main questions of investigations of the main index
      of carbohydrate metabolism--glucose in biological liquids of an organism.
      Detailed analysis of technological principles and interpretation of biochemical
      results with due regard to the influence of the complex of inner and external
      physico-chemical, biological and climatic factors is presented.

PMID- 8984803
TI  - [Possibilities and problems created by the development in human genetics].
AB  - During recent years a considerable development of our knowledge in human genetics
      has occurred, and the fine structure of the total human genome will be known
      within a few years. In the mean time genetic technology as part of medical
      genetics has already been introduced in our health care and numerous individuals
      and families faced with genetic problems will greatly benefit from that. Some new
      ethical problems, however, also arise and some of them are dealt with in the
      present article.

PMID- 8984804
TI  - [The systems process of reinforcement].
AB  - The process of reinforcement is considered in the context of the general theory
      of functional systems as an important part of behavioural act organization
      closely interacting with the dominant motivation. It is shown that reinforcement
      substantially changes the activities of separate neurons in different brain
      structures involved in dominant motivation. After a preliminary reinforcement
      under the influence of corresponding motivation the ribosomal apparatus of
      neurons begins to synthesize special molecular engrams of the action acceptor.
      The sensory mechanisms of reinforcement and, especially, the role of emotions are
      considered in details in the paper.

PMID- 8984805
TI  - [Current concepts of the neuromorphology and neurochemistry of the striatal
      cholinergic system and its role in regulating movement].
AB  - The recent neuromorphological and neurochemical data are reviewed concerning the
      organization of the striatal cholinergic system. A conclusion is made that the
      nigrostriatal dopamine and intrastriatal acetylcholine have the opposite effects
      on the main efferent outputs of striatum, including the expression of peptides
      which determines their involvement. The crucial role was proposed of the striatal
      cholinergic system in switching on and regulation of the so called indirect
      efferent pathway which controls the main striatal targets: the medial part of
      globus pallidus and reticular part of substantia nigra. On the basis of
      experimental and clinical data, we have suggested an important role of the
      activation of the striatal cholinergic system in the muscle tone control and the
      control of the main component of postural adjustment (unloading the working
      limb), in the inhibition of phasic components of a movement, and in the
      inhibition of unwanted movements during a behavioural task realization. The
      conclusion was experimentally supported about the possibility of changes in the
      motor behaviour, using the adequate pharmacological influence on the striatal
      cholinergic system. At the same time, the long-term fixed imbalance in the
      function of striatal efferent systems leads to a pathology of motor activity. The
      increase in the striatal cholinergic activity and/or decrease in the
      nigrostriatal dopaminergic effects may be the cause of Parkinson's disease.

PMID- 8984806
TI  - [The mathematical modelling of Ca2(+)-dependent postsynaptic processes in the
      hippocampus (the induction of long-term potentiation and long-term depression)].
AB  - The computational model was put forward of calcium-dependent posttetanic
      processes in the dendritic spine of CA3 hippocampal pyramidal neuron which
      received excitatory and inhibitory afferents. The system of differential
      equations enables description and evaluation of changes in protein kinase and
      protein phosphatase activity induced by changes in postsynaptic Ca2+ ion
      concentration (Cap2+). It was shown that the synaptic efficacy is determined by
      the ratio between active protein kinases and active protein phosphatase I.
      According to the proposed model, increase/decrease in Cap2+ concentration
      relative to the Cap2+ rise, produced by prior stimulation, results in the
      increase/decrease in the number of phosphorylated ionotropic receptors and in
      LTP/LTD synaptic efficacy. It follows form the model calculations that the same
      mechanisms underlie the LTP, LTD, and depotentiation. Some results of
      experimental study of the hippocampal and neocortical synaptic plasticity are
      explained and systematized.

PMID- 8984807
TI  - [The spatial organization of the EEG and individual psychological
      characteristics].
AB  - The influence of cognitive styles (analytic versus synthetic style, rigid versus
      flexible cognitive control, impulsivity versus reflexivity, field-dependence
      versus independence) on the information brain processes was estimated by means of
      analysis of spatial organization of cortical electrical activity (48 derivations)
      in 40 right-handed subjects (aged from 18 to 40) during their realization of
      verbal and non-verbal tasks using successive and simultaneous processing modes.
      Modulation of the "cognitive axis" (activity of the left anterior and right
      posterior cortical areas) was revealed connected with the factor of task
      subjective difficulty, especially in case of simultaneous processing mode. The
      combination of the synthetic cognitive style and flexibility of the cognitive
      control may be thought of as being the most favourable for the activation of the
      "cognitive axis" and utilization of the left- and right-hemispheric information
      processing, especially in non-standard situations.

PMID- 8984808
TI  - [The characteristics of the late reaction of the human brain to radiation
      exposure: the EEG and neuropsychological study (the sequelae of the accident at
      the Chernobyl Atomic Electric Power Station)].
AB  - We examined 23 patients (participants in the clean-up of the consequences of the
      Chernobyl accident in 1986-1987) using neuropsychological and
      electrophysiological approaches. The results obtained by means of EEG coherence
      analysis, three-dimensional source localization, and dichotic listening test were
      compared. All the patients showed some common dysfunctions such as disturbances
      of hemispheric interaction which resulted in deterioration of the brain
      functional state in comparison with the control group. Neuropsychological
      evidence and source localization of the epileptiform EEG suggested predominantly
      subcortical damage at the limbic-reticular and, especially, diencephalic level.
      The observed signs of the left-hemispheric dysfunction depended on the brainstem
      damage while the right-hemispheric dysfunction were explained by the diencephalic
      damage. The observed symptoms were considered as a result of subcortical brain
      lesions at different levels rather than the primary cortical hemispheric damage.

PMID- 8984809
TI  - [The spherical characteristics of acoustic space].
AB  - Theoretical analysis was performed of psychometric scaling of perception of the
      sounds and letters of the Russian language by the informants. It was shown that
      the score obtained are defined by the equation of the sphere in the N-dimensional
      mnemonic space. The common mechanisms is suggested of recipient's recognition of
      external stimuli in the visual and acoustic sensor systems by the method of
      positional predetector decoding.

PMID- 8984810
TI  - [The dynamics of the high-frequency components of brain electrical activity (up
      to 200 Hz) during learning reflects the functional mosaic structure of the
      neocortex].
AB  - The study was aimed to reveal frequency ranges of correlated changes of power
      spectral densities of the brain electrical activity (EA) including the high
      frequency components (HFC) in dogs (4 animals) by means of factor analysis
      technique. Spectral densities of EA in different cortical areas and olfactory
      bulb were factored. Relationships between the structure of the selected factors
      both by the parts of the total variance determined by them and their frequency
      loads suggest the regional and individual EA differences. In the process of
      learning (elaboration of motor skill of pressing the food-dispenser pedal with a
      forepaw) the factor organization of the EA became substantially more complicated,
      mainly, in the HFC-range (40-170 Hz). This was manifested in formation of
      narrower frequency subbands of the HFC each of which being highly loaded (0.7
      0.8) by one of the factors. The evidence obtained by means of the FA was
      completely verified using original version of cluster analysis.

PMID- 8984811
TI  - [The characteristics of the discrimination of the number of sequential signals in
      dogs].
AB  - Food instrumental asymmetrical differentiation (discrimination) between the
      reinforced train of five identical clicks administered with variable
      interstimulus intervals and the non-reinforced train of the same three clicks was
      elaborated in six dogs. At the stable stage of conditioning, the number of
      instrumental reactions to five clicks was twice higher than to three clicks.
      Temporal parameters of such kind of counting reactions are analyzed. A conclusion
      is made that dogs, can discriminate the number of identical signals in the
      consecutive train and use this parameter in their adaptive behaviour. Types of
      the internal inhibition which participate in the above-described differentiation
      are considered.

PMID- 8984812
TI  - [The functional asymmetry of the rabbit lateral hypothalamus during food
      motivation].
AB  - Thresholds and stability of food motivational reactions induced by
      electrostimulation of the left and right hypothalamus were studied in rabbits.
      Food reactions evoked by stimulation of the left hypothalamus had the lower
      thresholds and higher stability than those evoked by the stimulation of
      symmetrical areas. The asymmetry of the lateral hypothalamus in food reactions
      was not correlated with motor and sensory asymmetric.

PMID- 8984813
TI  - [The characteristics of the behavioral specialization of stably and unstably
      active nerve cells].
AB  - One of the characteristic features of neuronal activity during behaviour is
      correlation between the firing rate and determined current events at the
      behavioural level. The present work introduces comparative analysis of the
      activity organization in the neurons with more or less stable discharge patterns.
      The role of instability factor is discussed in the integration of elementary
      neurophysiological processes.

PMID- 8984814
TI  - [The effect of the phases of the estrous cycle on functional interhemispheric
      asymmetry in rats].
AB  - The functional interhemispheric asymmetry was studied in rats during different
      phases of the estrual cycle in the tests of emotional resonance (avoidance of
      pain cry of a conspecific) and the open field locomotor and exploratory activity.
      Inactivation of hemispheres was accomplished by potassium spreading depression.
      During the open field activity the left hemisphere dominated in proestrus, the
      right hemisphere dominated in estrus, in metestrus the dominance of the right
      hemisphere decreased, and in diestrus the hemispheric asymmetry was not
      expressed. The neocortex inhibited the emotional avoidance reaction in proestrus
      and facilitated it in estrus. The left hemisphere dominated in inhibition and the
      right hemisphere prevailed in activatory influence.

PMID- 8984815
TI  - [A comparative evaluation of the effect of removal of the epiphysis and damage to
      the amygdala on the behavioral reactions of rats].
AB  - Pinealectomy and lesions of the amygdala variously changed aggression of rats
      after social isolation and behavior in a conflict situation. It is suggested that
      the pineal gland by means of secreted melatonin suppresses the function of the
      limbic structures. It may regulate the pineal-amygdaloid relationships and play
      an important role in the organization of emotional behaviour.

PMID- 8984816
TI  - [The effect of stress on the anxiety level in female white rats at different
      stages of the estrous cycle].
AB  - Locomotor activity in the elevated plus-maze was studied in female white rats
      following chronic stress induction (measuring pain threshold in the course of 15
      20 days). Anxiety and plasma corticosterone levels were determined. In control
      experiments in intact rats anxiety was lower and locomotor activity was higher in
      proestrus than in diestrus. There were no differences in anxiety and locomotor
      activity between diestrus and proestrus in rats exposed to chronic stress. In
      intact rats plasma corticosterone levels were the same in proestrus and diestrus.
      Following chronic stress plasma corticosterone level was significantly higher in
      proestrus than in diestrus.

PMID- 8984817
TI  - [The effect of neural transplantation on audiogenic seizures in rats of different
      genetic strains].
AB  - The effects of neurotransplantation on development of audiogenic seizures (AS)
      were studied in Krushinskii-Molodkina (KM) rats genetically predisposed to AS and
      in Wistar rats especially selected for AS. Within 24 weeks after bilateral
      combined transplantation of the newborn striatum and cerebellum into the parietal
      cortex, the AS didn't develop in Wistar rats in 74% of tests. In control Wistar
      rats with cortical grafts or saline injections into the parietal cortex there
      were no significant changes in the AS development. In the experimental KM rats
      the grafting led to the 4-5-times increase in the AS latency. In 50% of rats it
      decreased the AS severity by 1-2. In the control KM rats these parameters didn't
      change. It was concluded that it was possible to suppress or decrease the AS
      development by the transplantation of the newborn striatal and cerebellar tissue
      into the cortex of rats predisposed to this kind of seizures.

PMID- 8984819
TI  - [Human positive brain potentials before visually evoked saccades].

PMID- 8984818
TI  - [The interaction of a state of haloperidol-induced catalepsy and a passive
      avoidance conditioned reflex].
AB  - Injection of haloperidol (2.5 mg/kg) immediately after elaboration of the passive
      avoidance conditioned reflex stabilized retrieval of the conditioned reflex on
      the 2nd, 7th, and 14th days. Catalepsy induced by haloperidol injection was
      increased after the completion of passive avoidance conditioning. Conditioned
      reflex retrieval decreased catalepsy which was retrieved without repeated
      haloperidol injection. In contrast to the control animals, in the animals after
      conditioning the most pronounced catalepsy was observed immediately after the
      conditioned reflex retrieval with the following stabilization at the lower level.
      The auto enhancement of catalepsy retrieval was more expressed on the 14th day
      (as compared with the 7th day) both in the control and learned animals, but in
      the latter it did not depend on the testing time (in contrast to the control
      animals.

PMID- 8984820
TI  - [The differential thresholds for 1-second time intervals].

PMID- 8984821
TI  - [The synchronization of cortical electrical activity at different levels of
      activation of the caudal reticular formation].

PMID- 8984823
TI  - [Toxic hepatitis due to dimethylformamide: case reports and literature review].
AB  - We report two patients with toxic hepatitis due to the solvent dimethylformamide
      (DMF). Other causes of hepatitis such as viral, drug induced or alcoholic
      hepatitis, could be excluded or were considered to be unlikely. Hepatotoxicity
      due to professional exposure to solvents e.g. dimethylformamide should be
      considered in any patient with unexplained hepatitis. The fast improvement of the
      clinical symptoms and the progressive normalisation of the liver function tests
      once the exposure to the product has been stopped, supports the diagnosis. Yet,
      non-drug induced toxic hepatitis remains an exclusion diagnosis. Therapy consists
      of avoiding every contact with the causative agent. Table 3 (Addendum) gives an
      overview of some industrial agents able to cause hepatitis.

PMID- 8984822
TI  - [NMDA receptors and the ultrastructural synaptic plasticity of the associative
      type in the rat neocortex].

PMID- 8984824
TI  - [Tubulointerstitial nephropathy with uveitis].

PMID- 8984825
TI  - Localization of types I and III collagen and fibronectin in the developing mouse
      palatal shelves.
AB  - The detailed distribution of types I and III collagen and fibronectin was studied
      in the developing mouse palatal shelf using a double immunofluorescence
      technique. Just prior to palatal shelf elevation, type I collagen showed denser
      localization on the nasal side than on the oral side of the middle hard palate
      region. Such a distribution extended as far as the posterior hard palate region
      but not to the soft palate region. In type III collagen and fibronectin, this
      uneven distribution was not so distinct even in the middle hard palate region
      during the same period. The correspondence of the most conspicuous region of this
      distribution of extracellular matrix components with the region of first shelf
      elevation suggests that the extracellular matrix, especially type I collagen,
      participates in palate development.

PMID- 8984826
TI  - Changes in the vascular network of the oral epithelium and reduced enamel
      epithelium during tooth eruption.
AB  - The purpose of this study was to examine the vascular network beneath the reduced
      enamel epithelium (REE) and oral epithelium (OE) during tooth eruption. Using the
      corrosive-resin casting method, vascular resin casts were prepared from premolar
      and molar teeth of the dog and examined by scanning electron microscopy. The
      vascular network beneath the REE is arranged in two layers, an inner layer
      consisting of a dense capillary network and an outer layer composed primarily of
      arterioles and venules. Throughout tooth eruption, the configuration of the
      vessels of the inner layer is continually changing from a network of capillary
      loops to a fishnet pattern, whereas the arrangement of the vessels of the outer
      layer remains fairly constant. When the crown emerges into the oral cavity,
      leakage of resin from the vessels provides evidence of increased vascular
      permeability, suggesting the presence of inflammation within the marginal
      gingiva. When root development is nearly complete, the vascular network adjacent
      to the REE becomes continuous with that of the OE. The inner margin of the free
      gingiva receives its blood supply from this network, and the vessels of this
      network also give off branches which anastomose with the capillary network of the
      periodontal ligament.

PMID- 8984827
TI  - Spermatophagy in the stallion epididymis: a scanning and transmission electron
      microscopy study.
AB  - The occurrence of phagocytosis of spermatozoa in the epididymis is a
      controversial issue in male reproductive biology. In this paper we documented, by
      scanning and electron microscopy, the presence of spermatophages in the lumen of
      the proximal region of stallion epididymis. Sperm phagocytosis involving the
      principal cells that line the cauda epididymidis region was also observed. The
      possible meaning of this process in the removal of damaged, aged or surplus
      spermatozoa is discussed. These observations were made in samples obtained from
      random cases, during the course of research work carried out on the stallion male
      seminal duct system.

PMID- 8984828
TI  - Immunophenotypic and ultrastructural evidence of the langerhans cell origin of
      the canine cutaneous histiocytoma.
AB  - Canine cutaneous histiocytoma (CCH), a histiocytic benign, dermal, self-healing
      tumor in the young dog, and epidermal Langerhans cells (LC) are thought to be
      related. In this study, we used immunohistochemical staining and transmission
      electron microscopy for 5 fresh CCH and 17 fixed tumors, to examine if, on the
      basis of their immunophenotype and their ultrastructural morphology, these tumor
      cells originate as LCs. The immunophenotype of CCH: canine CD11a, 11c, 18, 45,
      MHC II positive and ACM1, human CD14 negative, was different from canine
      macrophage immunophenotype but very similar to the canine LC phenotype.
      Furthermore, we have described ultrastructural markers in CCH cells for the first
      time: these consist of coated vesicles, regularly laminated bodies, pleiomorphic
      inclusions, paracrystalline structures, and deep invaginations of the plasma
      membrane, usually observed in congenital self-healing histiocytosis, a human LC
      tumor, or occasionally observed in human LC. The occurrence of such
      immunophenotype and ultrastructural markers confirmed the common lineage of LCs
      and CCH cells.

PMID- 8984829
TI  - Neuroepithelial bodies in relatively mature lungs: an investigation in prenatal
      and newborn lambs.
AB  - Lungs of fetal and neonatal lambs were found to contain small, inconspicuous and
      widely dispersed neuroepithelial bodies (NEB). Under the light microscope, NEB
      could only be identified with certainty by their positive immune reaction to
      antibodies against serotonin. At the ultrastructural level, a large number of
      dense-cored vesicles was found in the corpuscular cells of the NEB. However, the
      number of intracorpuscular nerve endings was small. We conclude from these
      findings that, in the lamb, NEB act primarily as local regulators of lung
      function and that their reflex-mediated actions may be of secondary importance.
      This may be related to the fact that lungs of lambs at birth are relatively
      mature compared to those of various other species. Increased maturation of lungs
      and a concomitant decreased risk of insufficient oxygenation might be associated
      with the presence of an oxygen-sensitive chemoreceptor with primarily local
      actions for prevention of hypoxia.

PMID- 8984830
TI  - Distribution of Escherichia coli heat-stable enterotoxin/guanylin/uroguanylin
      receptors in the avian intestinal tract.
AB  - Pathogenic strains of enteric bacteria secrete small heat-stable toxins (STs)
      that activate membrane guanylyl cyclase receptors found in the intestine. The
      intestinal peptide agonists, guanylin and uroguanylin, are structurally related
      to STs. Receptors for 125I-ST were found throughout the entire length of the
      intestinal tract of all the birds examined. These receptors were restricted to
      intestinal epithelial cells covering villi and forming intestinal glands and were
      not observed in other strata of the gut wall. The most intense labeling of
      receptors by 125I-ST occurred in the region of the microvillus border of
      individual enterocytes. There appeared to be a decrease in receptor density
      distally along the length of the small intestine, although labeling of receptors
      by 125I-ST was observed throughout the small intestine and colon. Cellular cGMP
      accumulation responses to Escherichia coli ST and rat guanylin in the domestic
      turkey and duck were greater in the proximal small intestine compared to the
      distal small intestine or colon. Brush border membranes (BBM) isolated from the
      mucosa of proximal small intestine of turkeys exhibited agonist-stimulated
      guanylyl cyclase activity. The rank order potency for enzyme activation was E.
      coli ST > uroguanylin > guanylin. Competitive radioligand binding assays using
      125I-ST and turkey intestine BBM revealed a similar rank order affinity for the
      receptors that was exemplified by the Kd values of ST 2.5 nM, uroguanylin 80 nM
      and guanylin 2.6 microM. It may be concluded that functional receptors for the
      endogenous peptides, guanylin and uroguanylin, occur in the apical membranes of
      enterocytes throughout the avian intestine. The receptor-guanylyl cyclase(s) of
      proximal small intestine were preferentially activated by uroguanylin relative to
      guanylin, but both endogenous peptides were less potent than their molecular
      mimic, E. coli ST.

PMID- 8984831
TI  - Hypertrophic Z-line observed in aged one-humped camel (Camelus dromedarius).
AB  - The ultrastructure of cardiac muscle from 3 aged one-humped camels (Camelus
      dromedarius) was examined to see if aged camels also develop hypertrophic Z-lines
      as observed in the heart of aged humans and other animals. The results proved
      that the aged camel heart develops hypertrophic Z-lines together with other age
      associated alterations, including loss of myofibrils and myofilaments, increase
      of intermyofibrillar spaces and intercellular spaces, and disruption of
      mitochondrial cristae and intercalated disc structure. Hypertrophic Z-lines are
      somewhat smaller than those of other species, but occur both in the atria and
      ventricles. Although the majority of cardiac muscle samples revealed a normal
      structure, the finding of hypertrophic Z-lines in camel heart is the first such
      observation in a ruminant animal. The anomalous camel muscle resembles that of
      other species in terms of cell alterations commonly associated with aged hearts.

PMID- 8984832
TI  - Proximal paraconal interventricular myocardial bridge in dog: ultrastructural
      characterization.
AB  - The ultrastructure of the dog myocardial bridges (MB), named here the proximal
      paraconal interventricular-myocardial bridge (PPI-MB), was examined to determine
      if its structure is identical to that of ordinary cardiac muscle. This study is
      preparatory to the establishment of PPI-MB as a physical and physiological model
      system to examine the influence of MB on coronary flow in cardiac function. Five
      of 46 dog hearts examined possessed PPI-MB, the occurrence of which was
      independent of sex, age and breed. The dog PPI-MB was localized in a limited area
      in the proximal third of the paraconal interventricular groove. PPI-MB myocytes
      and myofibrils were arranged quite straight and smooth, with minimum branching.
      PPI-MB myocytes formed side-by-side cell junctions through the mediation of
      mitochondria. Connective tissue elements were involved in terminal cell adhesion
      to form the myomyous junction beside the intercalated disc. The excitation
      conductive system of sarcoplasmic reticulum-T tubule often showed a triad.
      Numerous nerve axons or nerve ending-like structures appeared. Many structural
      views deviated somewhat from common cardiac muscle structure. This paper
      represents the first detailed description of PPI-MB muscle.

PMID- 8984833
TI  - Lysosomal changes in rat spinal ganglia neurons after prolonged treatment with
      cisplatin.
AB  - We performed morphometric and ultrastructural studies to determine the
      morphological response of rat spinal ganglion sensory neurons to prolonged
      administration of cisplatin up to a total dose of 18 mg/kg. We quantitated the
      different types of lysosomal system (LS) bodies present (primary and secondary
      lysosomes, lipofuscin granules) as well as multivesicular bodies in treated and
      control animals. Five rats were examined per group. This ultrastructural study on
      cisplatin-induced changes in LS of spinal ganglia neurons shows that the total
      area and total number of LS structures are significantly increased by cisplatin
      treatment. The main specific changes were increase in number of small-size
      lysosomes and increase in number of polymeric lipofuscin granules. Other
      alterations observed were presence of nucleolar segregation, patches of
      neurofilaments and deposits of osmiophilic material in the perikaryon and axon
      hillock, all indicating that sensory neurons are a major target of cisplatin.

PMID- 8984834
TI  - [Multifrequency tympanometry in Meniere's disease: preliminary results].
AB  - Tympanometry with 220 Hz probe tone mainly measures compliance related components
      of the middle ear. Only higher frequency probe tones provide information on mass
      related components. In order to study the behavior of the mass related components
      in endolymphatic hydrops, the Authors tested 15 Meniere's disease patients and 10
      healthy subjects using multifrequency tympanometry. In both groups tympanometry
      with 220 and 678 Hz probe tone was employed to evaluate resonance frequency. The
      presence of a "camel hump" ([symbol: see text]) pattern obtained with the 678 Hz
      probe tone test indicated an elastic tympano-ossicular system (low point of
      middle ear resonance); the presence of an inverted "V" ([symbol: see text])
      pattern showed a more rigid system (high point of middle ear resonance). In
      Meniere's disease carriers multifrequency tympanometry revealed 21 ears (70%)
      with a resonance frequency higher and 6 (20%) lower than 678 Hz. Three patterns
      (10%) were not classifiable. In the healthy group resonance frequency resulted
      lower than 678 Hz in 23 ears (57.5%); in 13 ears higher (32.5%). Four patterns
      (10%) were not classifiable. In Meniere's disease carriers the tympanometric
      patterns found with 678 Hz probe tone indicated the presence of a more rigid
      tympano-ossicular system.

PMID- 8984836
TI  - [Free-flap fibula for the reconstruction of composite mandibular defects].
AB  - The advent of microsurgery has revolutionized the reconstruction of composite
      tissue defects of the mandibular region. Well-vascularized bone and soft-tissues
      can be used to repair any kind of oromandibular defects and many of the
      morphological and functional goals of mandibular reconstruction can now be
      achieved. The ideal flap should provide a vascularized bone of sufficient length
      and height, easily shaped to match the original mandible with a thin, abundant
      soft-tissue component. The donor site morbidity should be minimal and a two-team
      approach possible. Different flaps have been used for mandibular reconstruction
      including fibula, iliac crest, radius and scapula. According to us, fibula free
      flap satisfies many of these requirements and is the flap of choice in most cases
      of difficult mandibular reconstruction. 8 fibula free flaps were used in 6 cases
      of primary and 2 cases of secondary reconstructions. The defects were secondary
      to resections of oral cancers in 4 cases and of osteosarcomas in 4 cases. The
      mandibular defects were between 8 and 16 cm in length. Multiple osteotomies were
      used to shape the bone and miniplates were utilized for rigid fixation of the
      osteotomized bone and of the remaining mandible. An important soft-tissue defect
      was present in 6 cases requiring a skin paddle for oral lining. In 6 cases there
      was a complete survive of the flaps with very satisfactory results and good
      mandibular contour. There was one flap failure for a venous thrombosis and in one
      case the flap was removed after 8 days for complications independent of the
      microvascular technique. Donor site morbidity was minimal with no significant
      gait disturbance. In conclusion, the advantages of microvascular surgery and the
      reliability of fibula free-flap make it an attractive and versatile option in one
      stage reconstruction of composite tissue defects in the mandibular region.

PMID- 8984835
TI  - [Anterior cranio-facial resection for malignant tumors: report of 91 cases].
AB  - Between 1987 and 1994 we performed 103 anterior cranio-facial resections in
      patients affected by tumors involving the ethmoid, the nasal cavities and,
      sometimes, the orbit, the maxillary and sphenoid sinuses. The cibriform plate was
      always involved. The tumor invaded the frontal dura in 20 patients without
      intradural neoplastic vegetations. These were present in 6 cases. Ninety-one of
      these patients had a malignant tumor; from the histologic point of view we had 50
      adenocarcinomas, 16 epidermoid carcinomas, 8 estesioneuroblastomas, 6 adenoid
      cystic carcinomas, 5 melanomas and 6 infrequent types. The surgical technique
      became simplier in the second half of our patients. Now we perform a coronal skin
      incision and prepare a pericranial flap without the galea and use it to
      reconstruct the cranial base defect without bone or alloplastic material. The
      frontal craniotomy is rectangular, low and made by an oscillating saw without
      trephine holes. The posterior section of the skull base for a typical ethmoid
      tumor is always on the sphenoid roof and the lateral ones on the medial third of
      the orbital roof, al least in the more interested side. The anterior section is
      on the frontal sinus floor. The osteotomies may be enlarged according to tumor
      extension. Our facial incision is paranasal without splitting of the upper lip,
      but sometimes we used wider skin incisions and osteotomies for tumors involving
      the maxillary sinus and palate. We had many important complications in the first
      half of out patients with 7 postoperative deaths but none in the second half.
      Fifty-five percent of the adenocarcinomas, 7% of the epidermoid carcinomas, 75%
      of the estesioneuroblastomas, 100% of the adenoid cystic carcinomas and 0% of the
      melanomas are alive and well. Forty-six patients were previously treated
      elsewhere and 45 were untreated. The cure rate of these two groups of patients is
      very different: 38.1% of the first versus 61.9% of the second ones are alive and
      free of disease. Our experience proves that every transfacial or transnasal
      resection of an ethmoidal tumor involving the cribriform plate must be avoided.

PMID- 8984837
TI  - [High-dose carboplatin superselective intraarterial chemotherapy in advanced head
      and neck cancer].
AB  - Advances in vascular radiology techniques for superselective transfemoral
      arterial infusion prompted us to evaluate the effects of high-dose rapid regional
      carboplatin infusion for patients with advanced head and neck squamous cell
      carcinomas. Twenty untreated patients received three infusions of carboplatin
      (300-350 mg/m2) every 2 weeks with this method. All the infusions were performed
      without any complication. Treatment was well tolerated, with moderate (Grade 1-3
      WHO) local toxicity (stomatitis, dermatitis and alopecia) and minimal (Grade 1-2
      WHO) myelosuppression. The total response index (complete response plus partial
      response) was 94% for primary tumors and 50% for neck metastases. Neoadjuvant
      chemotherapy employing superselective rapid infusion of high-dose carboplatin is
      a feasible, relatively nontoxic, effective technique and may have important
      applications in multimodality therapy of untreated patients with advanced head
      and neck cancer.

PMID- 8984838
TI  - [External radiotherapy in early stage squamous cell carcinoma of the supraglottic
      larynx. Report of 28 cases].
AB  - The Authors reviewed a group of 28 pts with early-stage supraglottic carcinoma
      (T1-T2N0), classified according to UICC (1987), and treated exclusively with
      radiotherapy (RT) between 1980 and 1991. Until 1990 RT was employed for such
      tumors when surgery was refused or controindicated, while since 1991 primary
      irradiation (with surgery in reserve) has been considered the treatment of
      choice. The total dose ranged from 66 to 70 Gy on the larynx and up to 50 Gy on
      neck nodes. RT was applied in a daily fraction of 2 Gy five times a week. No
      significant early complications were observed. Only 1 pt showed residual cronical
      oedema in the arytenoid region. In none of the pts was tracheostomy necessary.
      The local control rate obtained after 30 months was 85.7% (24/28). Salvage
      surgery (horizontal supraglottic laringectomy, HSL) was performed in 3 out of 4
      pts with local failure and achieved complete control of the disease. In the last
      pt the surgery was controindicated because of poor general health conditions. The
      actuarial survival rate after 5 years is 86.2%. The present series was compared
      to a group of 152 pts with T1-T2N0 supraglottic cancer treated surgically (HSL)
      at the same Istitution. In these pts local control and the actuarial survival
      rates are 85.6% and 89% respectively. According to recent Literature data, the
      present findings confirm that RT may be administered for the treatment of
      selected early stage (T1-T2N0) supraglottic squamous cell carcinoma of the larynx
      with oncologic results equivalent to those obtained with radical surgery. The
      importance of imaging techniques (TC, MRI) in the correct staging of the tumor is
      emphasised.

PMID- 8984839
TI  - [Early stages of laryngeal cancer (I-II stage) and therapeutic options: case
      report and review of literature].
AB  - Between 1987 and 1993, 36 patients with early squamous cell carcinoma of the
      larynx (I-II stage) were treated with radiotherapy, at the National Institute for
      Cancer Research of Genoa; 25 patients were stage I (5 T1N0 of supraglottic
      larynx, 15 T1aN0 and 5 T1bN0 of glottic larynx) and 11 patients stage II (7 T2N0
      of supraglottic larynx and 4 T2N0 of glottic larynx); there were 32 males (89%)
      and 4 females (11%), ages ranging from 34 to 83 years (mean age 61 years). The
      radiotherapy was performed utilizing the X-ray of a 6 MV linear accelerator, with
      a daily conventional fractionation and a dose of 66-70 Gy/33-35 fr./7 weeks, with
      co-axial latero-lateral beams including cervical lymph-nodes, except for T1N0
      glottic cancer. The median follow-up was 51 months (range 8-84 months). The local
      control rate of all the patients was 80.5% at 51 months. According to the stage
      and tumor subsite, it was 80% for stage I a-b of the glottic site, 60% for the
      stage I of supraglottic site, 91% for stage II of supraglottic and glottic site.
      Only 6 patients (18%) underwent the salvage surgery and in all the patients the
      illness was under control. The overall survival rate was 83.3% at 51 months (4
      patients died of a second tumor (11%) and 2 from heart disease (5.5%)). The only
      complication we observed was a glottic edema. The analysis of our results
      demonstrates that radiotherapy seems to be more appropriate in the T1a-b glottic
      cancer. These results are in agreement with those obtained by other studies. On
      the contrary, the results obtained with radiotherapy, in the T2N0 glottic cancer,
      are not satisfactory, with regard to local control, as those obtained with
      surgery, but offers best functional results. In most T2N0 tumors, after the
      failure of radiotherapy, a reconstructive laryngectomy is still possible. We also
      obtained good results with the supraglottic lesions. The small number of cases we
      treated does not allow us to achieve final conclusions and other studies are
      necessary to confirm our results.

PMID- 8984840
TI  - [Panendoscopy in the research of multiple malignant synchronous occult tumors in
      patients with cancer of the upper aero-digestive tract].
AB  - The Authors consider the result obtained in the diagnosis of malignancies
      simultaneous neoplasia in patients with a tumour of the head and neck. The study
      was conducted on 337 patients on 750 observed in the last seven years with a
      squamous-cell carcinoma at different stages of keratinization, who underwent an
      ORL examination, bronchoscopy and esophagogastroduodenoscopy, sometimes with
      intravital staining. Bronchoscopy was conducted on 297 patients,
      esophagogastruoduodenoscopy on 300. Altogether 260 were subject to both
      techniques and 77 to only one procedure. Endoscopy released a second tumour in 4
      cases on 297 (1.34%) of the bronchus and in 5 cases on 300 (1.66%) of the
      esophagus. The percentage amounts to 3.46% in 260 patients subject to both
      examinations. Our study released a malignancies cells (18 cases on 216); this
      number was not confirmed by istological examination on bronchial biopsy. Our
      collaborators consider this result as pollution derived from cells coming from
      clear tumour in expansion. Our study, obtained from a substantial number of
      cases, justify the use of panendoscopy screening in conjunction with routine
      studies; although this procedure is aggressive, it is acceptable, because these
      second tumours have been discovered in early and asintomatic stage and were not
      found in the radiological examination.

PMID- 8984841
TI  - [Mucocele of sphenoid sinus: presentation of 3 cases].
AB  - Sphenoidal mucoceles are equally distributed between males and females occur
      rarely and have an incidence of 1%. Their low incidence is certainly to be
      ascribed to their deep position with respect to the superior respiratory tract as
      well as to the characteristics of the mucosa coating of the sinus (where the
      scarce muciparous component does not cause drainage problems). During endocranial
      manifestation, it is important to make a differential diagnosis between tumors at
      the base of the skull and adenomas of the hypophysis. The most feasible
      etiopathogenetic hypotheses are insufficient drainage of the sinus, cystic
      degeneration of the ghiandolar epithelium, presence of embryonal remnants and
      previous surgery. The Authors report three cases of mucoceles located in the
      sphenoid, two of which with destruction of the sellar floor and upward invasion,
      one with posterior invasion and involvement of the clivus. Sphenoidal mucoceles
      generally tend to spread more frequently in an anterior-inferior fashion with
      invasion of the etmoid, the nasal fossae and the rhinopharynx. In some cases we
      observe upward invasion with destruction of the sellar floor, as in the first two
      patients. There may by an invasion in the orbital cavity when spreading occurs
      sideways. More rarely, the intermediate cranial fossa is invaded through the
      lateral wall and the posterior cranial fossa through the posterior wall.
      Therefore, it is evident that an early diagnosis is always desirable because it
      may spare the patient the neurological manifestations resulting from the
      evolution of the disease. The treatment for a sphenoidal mucocele is surgical.
      The Authors report a synthesis of the surgical techniques most frequently used by
      otorhinolaryngologist and neurosurgeons, and present a critical analysis of the
      cases presented.

PMID- 8984842
TI  - [Parapharyngeal oncocytoma of the parotid gland].
AB  - Oncocytic tumors rarely occur in major salivary glands and generally account for
      less than 1% of all salivary tumors. Oncocytomas are infrequent tumors that most
      commonly arise in the salivary, thyroid, parathyroid and pituitary glands,
      kidneys and pancreas. They are rarely malignant. Oncocytic differentiation may
      also occur focally in a benign or a malignant epithelial tumor, such as a thyroid
      adenoma, papillary cystadenoma lymphomatosum and mixed tumors of salivary glands,
      malignant carcinoids of the bronchus, adrenal cortical carcinoma, and renal cell
      carcinoma. The term oncocytoma refers to a single neoplasm contrast to nodular
      oncocytic hyperplasia, which refers to two or more distinct tumor nodules, and to
      oncocytic mucoepidermoid carcinomas, where there is evidence of infiltrative
      growth and malignant of clinical behavior. We here report surgical treatment and
      light and electron microscopical findings obtained in the case of an oncocytoma
      of the parapharyngeal prestyloid space in a 62-year-old man who was admitted to
      our Department because of a slowly enlarging, painless mass in the pharyngeal
      extension of the right parotid gland. The mass has distorted the isthmus of the
      fauces, compressing the contra lateral pharyngeal-palatal plica. A total right
      parotidectomy which spared the branches of the facial nerve was performed. During
      the operative procedure, tissue was removed for frozen-section examination. The
      patient had an uneventful post-operative course. For all that has previously been
      written about oncocytic tumors, relatively very little is known of their
      etiology. In the past a correlation was made between the etiology and the history
      of direct or indirect radiation exposure. As oncocytic metaplasia and oncocytomas
      are often seen most in older individuals, the oncocyte was previously regarded as
      a "functional exhaustion" of a normal cell. As far as we concerned, the preferred
      method of surgically exposing the parapharyngeal-prestyloid space is that of
      removing the parotid gland through a cervical approach. Because of the proximity
      of certain anatomical structures, the transoral approach is not the most
      suitable.

PMID- 8984843
TI  - [Plasmacytomas of the head and neck].
AB  - Neoplastic proliferation of plasma cells results in a population of
      immunologically homogeneous cells that can produce diffuse (multiple myeloma) or
      localized (extramedullary plasmacytomas and solitary plasmacytoma of bone)
      disease. In otorhinolaryngologic literature these neoplasms are rarely described
      and their nosological arrangement is often confused. The presence of a plasma
      cell neoplasm can be a surprise and sometimes a diagnostic challenge to the head
      and neck surgeon. Proper management of such lesions needs to be individualized
      according to their expected biologic behaviour. The recent observation of a case
      of maxillary sinus plasmacytoma suggested the Authors to carefully review the
      literature, drawing their attention mainly on the current histogenetic hypotheses
      and their consequences in therapeutic strategy. The correct diagnostic procedure
      is also explained, highlighting the difficulties due to both the protean nature
      of the disease and the still existing nosological confusion. The possibility of a
      plasma cell tumour should be never forgotten in presence of an head and neck
      neoplasm. Because these neoplasms may signal the presence of multiple mieloma,
      full evaluation is required to exclude disseminated disease. In light of recent
      histogenetic acquisitions it is suggested that extramedullary plasmacytomas can
      be classified among the so-called "mucosa-associated" lymphomas. Possible
      following differences in therapeutic approach and long-term follow-up are also
      indicated, stressing the role of surgery in managing these disorders. Surgical
      excision of extramedullary plasmacytomas followed by complementary radiotherapy
      on the site of tumour is proposed as the best treatment for these kind of
      neoplasms. This is in opposition with "classical" statement considering
      radiotherapy the only treatment for this kind of disorders.

PMID- 8984844
TI  - [The historic corner. Francesco II of Valois: a historic case of otogenic
      meningitis].

PMID- 8984845
TI  - [Letter to the editor].

PMID- 8984846
TI  - [Letters to the editor].

PMID- 8984847
TI  - Kinetics of hydrolysis of ceftazidime in aqueous solutions.
AB  - The kinetics of hydrolysis of ceftazidime in aqueous solutions at 323 K, 333 K,
      343 K and 353 K over the pH-range (0.43-9.76) and at 295 K, 303 K and 308 K over
      the pH-range (9.17-13.16) has been investigated. The decomposition was followed
      by HPLC and UV spectral methods. The pH-rate profile was accounted for by the
      specific acid catalyzed reactions and also by assuming spontaneous water
      catalyzed decomposition of molecule ceftazidime in various grade of dissociation.
      Various buffer substances were found to exhibit general acid and base catalysis
      of the degradation. Thermodynamic parameters of the reaction: energy, entropy and
      enthalpy of activation and the frequency factor for the specific rate constants
      were determined.

PMID- 8984848
TI  - The influence of carbohydrates and polyhydric alcohols on the stability of
      ceftazidime in aqueous solution.
AB  - The kinetics of degradation of ceftazidime in aqueous solutions containing
      various carbohydrates (glucose and fructose) or polyhydric alcohols (sorbitol and
      mannitol) was investigated over the pH range 9.92-10.93 at 35 degrees C. A
      relationship between the degradation rate and the hydroxy compound concentration
      was observed at each pH studied, and the rate-accelerating effect of the
      compounds was directly proportional to the hydroxide ion activity.

PMID- 8984850
TI  - [Prevalence of mental disorders in childhood in pediatric primary care].
AB  - This research is conducted in two stages with an epidemiological methodology. The
      population of the study is composed of boys and girls aged between 6 and 11 years
      old, who seek a consultation in a Primary Care Paediatric Centre for a period of
      three months (point prevalence, one day prevalence). In the first stage, the
      Achenbach CBCL is used as screening instrument, and in the second stage, the ESPI
      clinical interview with DSM-III-R criteria. The CBCL acts as an adequate
      screening instrument for a cross-section corresponding to p 70 in this sample.
      The emotional disturbances in this paediatric population are a 30.2% rate of
      prevalence, of which only less than half are forwarded to a Child Mental Health
      Service.

PMID- 8984849
TI  - [Risperidone in the treatment of chronic schizophrenia: multicenter study
      comparative to haloperidol].
AB  - OBJECTIVE: This study was designed to compare the efficacy and safety of five
      different doses of risperidone with a fixed dose of haloperidol in patients with
      chronic schizophrenia. METHOD: After a 1-week single-blind, placebo washout
      phase, 99 chronic schizophrenic patients were randomly assigned to double-blind
      treatment with 1, 4, 8, 12 or 16 mg risperidone or 10 mg haloperidol daily for 8
      weeks. Efficacy was assessed throughout the study by the Positive and Negative
      Syndrome Scale (PANSS) for schizophrenia, and Clinical Global Impression (CGI).
      Safety assessments included the Extrapyramidal Symptom Ratinf Scale (ESRS) UKU
      Side Effect Rating Scale, vital signs, body weight, ECG and laboratory screening.
      RESULTS: Risperidone had a bell-shaped dose-response curve, with optimal
      therapeutic responses occurring at a daily dose of 8 mg. The therapeutic response
      to haloperidol was similar to that seen with risperidone 16 mg. Risperidone was
      associated with significantly less extrapyramidal symptoms than haloperidol, as
      assessed by the ESRS. The effect was mirrored by the requirement for
      antiparkinson rescue medication. Furthermore, the overall incidence of adverse
      events was markedly lower with the optimum dose of risperidone than with
      haloperidol. CONCLUSIONS: Risperidone is at least as effective as haloperidol for
      the treatment of chronic schizophrenia. Moreover, risperidone is associated with
      an improved adverse event profile and significantly less extrapyramidal symptoms
      which will have beneficial implications on patient quality of life and
      compliance. These results are in agreement with the results from the
      international multicenter trial.

PMID- 8984851
TI  - [The concept of delirium in Spanish psychiatry (19th-20th century)].
AB  - The history of psychiatric knowledge in Spain can be divided into four
      differentiated periods (up to the eighteenth century; nineteenth century; first
      third of the twentieth century and the two final thirds). These four periods
      provide a framework within which theories about delusion can be explored. Spanish
      psychiatrists have not been very original. Nonetheless, some of them (Sanchis
      Banus, Lopez Ibor, Martin Santos, Llopis, Valenciano, Sarro or Castilla del Pino)
      have tried to make personal contributions to the subject of delusion that deserve
      attention. Their theories (and some others) are reviewed in this paper.

PMID- 8984852
TI  - [Seasonal affective disorder and light therapy].
AB  - Seasonal affective disorders (SAD) represents a subgroup of major depression with
      a regular occurrence of symptoms in autumn and winter and full remission in
      spring and summer. Light therapy or phototherapy has become the standard
      treatment of this type of depression. The phototherapy is affective therapy for
      depressive symptoms of SAD. However, the action mechanism of light therapy is
      uncertain. Finally, new lines of the investigation of light therapy are
      aforementioned.

PMID- 8984853
TI  - [Biochemical changes in cerebrospinal fluid associated with the neurotoxic action
      of HIV-1].
AB  - The aim of this study is to evaluate the usefulness of different markers to
      diagnose neurologic and psychiatric diseases due to HIV-1 infection Increased
      concentration of quinolenic acid has been implicated in the neurologic deficits
      and brain atrophy that may accompany infection with the HIV-1 virus. CFS
      concentrations of quinolenic acid have been implicated in the pathogenesis of the
      AIDS dementia complex. Cytokines liberation are very altered and this factor may
      be correlated with direct toxicity about central nervous system cells. Also are
      increased the values of neopterin. In the different stages of AIDS, the highest
      values are obtained in dementia complex. Neopterin, tryptofan and kinorenina, in
      blood and CFS are directly correlated with neurologic and psychiatry
      sintomatology. The highest values of soluble intercellular adhesion molecule 1
      are found in HIV encephalopathy As well as are important the values, in CSF and
      blood of beta-2-M, Ag HIV, Ac41, tumor necrosis factor-alpha in the neurologic
      disease in HIV-1 infection

PMID- 8984854
TI  - [Neuropsychological involvement in childhood epilepsy].
AB  - Children with epilepsy are at risk for developing learning problems. The poor
      academic achievement shown by children with epilepsy may result from the
      underlying cognitive deficits. The study of such problems reveals the implication
      of several factors that determine the nature and degree of the neuropsychological
      defects. Among the most frequently reported factors are epileptic factors such as
      age of onset, type of seizures, duration, localization of cerebral dysfunction,
      frequency, antiepileptic treatment, and etiology.

PMID- 8984856
TI  - [Bladder hernia apropos of a case report].
AB  - The authors report a case of bladder hernia associated to prostatic benign
      hyperplasia. The diagnosis is confirmed by intra-venous urogram and computed
      tomography imaging. The reintegration of the bladder in the abdomen was performed
      in association to endoscopic resection of the prostate. Bladder hernia is rare
      condition. Surgical treatment of bladder hernia is associated to the etiology
      (prostatic benign hyperplasia...) of the hernia to prevent recurrence.

PMID- 8984855
TI  - [Liposarcoma of the spermatic cord].
AB  - The liposarcoma is mainly located in the retroperitoneum and rarely involves the
      spermatic cord. Dissemination occurs more often via haematogenous way than by
      lymphatic way. The incidence of local recurrence is higher than distant
      metastases. The treatment of choice is the wide excision. Adjuvant radiotherapy
      is recommended in the well differentiated and myxoid type of tumors if the local
      control during excision is not complete or wide enough. Benefit of chemotherapy
      is still controversial and limited. Case report of a stage 1 liposarcoma of the
      spermatic cord, four years after excision of a large lipoma during a hernia
      repair. The treatment consisted in radical excision of this liposarcoma without
      any adjuvant therapy. Follow-up of 30 months without recurrence.

PMID- 8984857
TI  - Technology Scorecard: are you up to date?

PMID- 8984858
TI  - A nurse wins her battle to ban FGM.

PMID- 8984859
TI  - The effect of epidural opioids on maternal oxygenation during labour and
      delivery.
AB  - The effects of epidural fentanyl on the incidence of maternal hypoxaemia during
      labour and on neonatal welfare were examined. Women were randomly allocated to
      receive one of two epidural infusions, bupivacaine 0.125% alone or bupivacaine
      0.0625% with 2.5 micrograms.ml-1 fentanyl, and maternal arterial oxygen
      saturation was monitored continuously until delivery. The median incidence of
      desaturation (SpO2 < 95%) during the active phase of the second stage of labour
      was significantly greater in the fentanyl group than in controls (2.9 versus 0.6
      min.h-1, p = 0.02). Similarly, the incidence of desaturation to SpO2 < or = 90%
      was greater in the fentanyl group than in controls (p = 0.02). There was no
      correlation between maternal oxygenation or plasma fentanyl concentration and
      neonatal welfare as measured by umbilical arterial and venous blood gas and acid
      base status, Apgar score and Neurologic and Adaptive Capacity Score.

PMID- 8984860
TI  - The estimation of inspired desflurane concentration in a low-flow system.
AB  - We have examined the predictability of inspired desflurane concentration during
      low-flow anaesthesia using a to-and-fro breathing system. Twenty-two adult
      patients requiring mechanical ventilation of the lungs during surgery took part
      in the study. Using a fresh gas flow of 1 l.min-1, the ratio of inspired
      desflurane concentration to desflurane vaporizer setting was found to be
      approximately 0.75 after 9 min of anaesthesia and at 2 l.min-1 fresh gas flow the
      ratio was approximately 0.9 after 2 min of anaesthesia. These ratios were
      maintained throughout the procedure, except for a few minutes following each
      change in vaporizer setting.

PMID- 8984861
TI  - A survey of emergency airway management in the United Kingdom.
AB  - A postal questionnaire aiming to ascertain the availability of cricothyrotomy and
      transtracheal ventilation equipment, and experience of its use, was sent to all
      tutors of the Royal College of Anaesthetists in the United Kingdom and Ireland.
      The response rate was 74.9%. Almost half of the respondents had experience of
      cricothyrotomy. The 'Portex Minitrach' (58.6%) was the most commonly used
      preformed device, followed by the 'William-Cook' cannula (8.5%). The 14-G
      intravenous cannula (21.1%) was the most frequently improvised cricothyrotomy
      device. Seventy six percent of all theatres had equipment available for such
      emergency airway management. Sixty five percent of Portex-Minitrach insertions
      resulted in complications, more than half of which were serious (total failure to
      cannulate (17.1%), multiple attempts (20.7%), pneumothorax (8.5%) and severe
      bleeding (7.3%)). Major complication rates of the 'William-Cook' device and 14-G
      intravenous cannula were 27.3% and 22.2% respectively. Seventy five percent of
      patients reported had eventual successful airway management with full recovery,
      while 9.6% had partial recovery and 15.4% died. Formal training of emergency
      airway management was practised in 14.2% of anaesthetic departments, while 73.6%
      had informal training. Twelve percent of the departments did not specifically
      teach their trainees the skill of emergency airway management.

PMID- 8984862
TI  - A comparison of the forces exerted during laryngoscopy. The Macintosh versus the
      McCoy blade.
AB  - The forces exerted at laryngoscopy with the McCoy and Macintosh blades have been
      compared in 40 patients. The variables measured were the duration of
      laryngoscopy, the three maximally-applied forces and the mean force. The mean
      (SD) forces recorded were 18.9 (7.82) and 10.1 (5.33) N, respectively, with the
      Macintosh and the McCoy blades (p < 0.001) with a similar duration of
      laryngoscopy. There was a significant positive correlation between the mean force
      and patients' weight, height and body mass index for the Macintosh blade but only
      for weight and height for the McCoy blade. It is concluded that the use of the
      McCoy blade results in significantly less force being applied during
      laryngoscopy. This may be the reason for the reduction in the stress response
      reported previously with the use of the McCoy blade.

PMID- 8984863
TI  - Effect of transcutaneous electrical nerve stimulation on onset of axillary plexus
      block.
AB  - We examined the effect of high frequency transcutaneous electrical nerve
      stimulation on the onset of brachial plexus block. Three groups of patients
      scheduled for surgery of the hand had a local anaesthetic block performed with 40
      ml mepivacaine 1.5% using the axillary approach. After injection of the local
      anaesthetic transcutaneous electrical nerve stimulation was applied for 15 min
      either to the median nerve or the ulnar nerve; no stimulation was applied in the
      control group. Before and for 45 min after, the injection of local anaesthetic
      touch perception, pin prick, motor strength and skin temperature were tested by a
      blinded investigator in the areas supplied by the median, musculocutaneous,
      radial and ulnar nerves. There were no differences in the onset of block between
      the groups. Thus, the frequency-dependent action of local anaesthetics could not
      be demonstrated.

PMID- 8984864
TI  - Lack of efficacy of intra-articular opioids for analgesia after day-case
      arthroscopy.
AB  - A randomised double-blind placebo-controlled trial was undertaken to assess the
      analgesic efficacy of intra-articular opioids following arthroscopy of the knee.
      At the completion of surgery, patients received an intra-articular injection of:
      morphine 1 mg, buprenorphine 30 micrograms or 0.9% saline. There were no
      differences in pain scores among groups for the first 24 h postoperatively. We
      have found no clinical evidence for a peripherally-mediated opioid analgesic
      effect.

PMID- 8984865
TI  - The effect of introducing fibreoptic bronchoscopes on gas flow in laryngeal masks
      and tracheal tubes.
AB  - The laryngeal mask airway, reinforced laryngeal mask airway and tracheal tube
      were studied to determine (1) flow resistance during simulated inspiration and
      (2) the maximum size of fibreoptic scope which can be passed down the lumen at
      clinically useful ventilatory settings. In addition, the flow resistance imposed
      by the mask aperature bars was quantified. The laryngeal mask airway can
      accommodate a larger fibrescope than the corresponding sizes of reinforced
      laryngeal mask airway or tracheal tube. Mean (range) flow resistance was 2.3 (1.7
      3.5) times higher with the reinforced laryngeal mask airway compared to the
      laryngeal mask airway, 2.1 (1.2-4.2) times higher with the tracheal tube compared
      with the laryngeal mask airway and 1.2 (0.7-1.8) times lower with the tracheal
      compared with the reinforced laryngeal mask airway. Removal of the mask aperture
      bars resulted in a mean decrease in flow resistance of 3.6%. Our data have shown
      that the laryngeal mask airway can accommodate a larger fibrescope than either
      the reinforced laryngeal mask airway or tracheal tube at clinically useful
      ventilatory settings and that the current recommendations for maximum size of
      fibrescope should be revised.

PMID- 8984866
TI  - Neuromuscular and cardiovascular advantages of combinations of mivacurium and
      rocuronium over either drug alone.
AB  - We investigated isobolic mixtures of mivacurium and rocuronium to determine if
      the combination offered any advantages over either drug alone. We used five dose
      regimens to achieve ED95 x 2: [(1.5 x ED95 mivacurium) + (0.5 x ED95 rocuronium);
      (1 x ED95 mivacurium) + (1 x ED95 rocuronium); (0.5 x ED95 mivacurium) + (1.5 x
      ED95 rocuronium); (2 x ED95 mivacurium); (2 x ED95 rocuronium)]. We studied onset
      time, duration of block, recovery of block, arterial blood pressure and heart
      rate. Mivacurium alone produced the block of shortest duration (p < 0.001). Onset
      time was shortest in the rocuronium alone group and was significantly faster in
      all the rocuronium treated groups compared to mivacurium alone (p < 0.001).
      Arterial blood pressure and heart rate decreased transiently in the mivacurium
      alone group but not in the other groups. These results demonstrate increased
      cardiovascular stability and more rapid onset of block with combinations of
      mivacurium and rocuronium without significant prolongation of the block.

PMID- 8984867
TI  - Configuration of the SCOTI device with different tracheal tubes.
AB  - We have evaluated the Sonomatic Confirmation of Tracheal Intubation device
      (SCOTI) by testing its ability to be correctly configured with a variety of
      tracheal tubes of differing internal diameter and length. The device only
      configured correctly for RAE tubes with internal diameter of 7.0 mm or greater
      and for armoured tubes of internal diameter 8.5 mm. For conventional tubes of
      varying internal diameter cut to different lengths, configuration was only
      successful with certain dimensions. The inability to configure the device
      correctly with all types and lengths of tracheal tubes limits its usefulness as a
      indicator of tracheal intubation.

PMID- 8984868
TI  - Simulated difficult intubation. Comparison of the gum elastic bougie and the
      stylet.
AB  - A randomised study was carried out to compare the efficacy of the gum elastic
      bougie and the stylet in a simulated difficult intubation. A laryngoscopic
      assessment, as described by Cormack and Lehane, was made in 100 patients. A Grade
      3 view was then simulated. In the Bougie First Group (50 patients) two attempts
      were made to pass a gum elastic bougie and a tracheal tube into the trachea. If
      these first two attempts were not successful, two further attempts at intubation
      were allowed with a stylet placed in the tracheal tube. In the Stylet First Group
      (50 patients) the order was reversed. After two attempts the tube was correctly
      placed in the trachea in 96% of cases in the Bougie First Group compared to only
      66% of cases in the Stylet First Group (p < 0.001). We recommend that a gum
      elastic bougie should be readily available and that anaesthetists should use it
      in preference to a stylet whenever a good view of the glottis is not immediately
      available.

PMID- 8984869
TI  - Anaesthesia with the Boyle's bottle vaporizer.
AB  - Having used the Boyle's bottle vaporizer apparatus out of necessity in a
      developing country, the concentration of agent that had been administered was
      investigated retrospectively. Three anaesthetic agents, halothane, isoflurane and
      enflurane, were measured at different temperatures, using a Boyle's anaesthetic
      machine and a Boyle's bottle in circuit with a Magill breathing system connected
      to a Rascal II Agent Monitor. Bubbling a fresh gas flow of 5 l.min-1 through the
      anaesthetic liquids generated concentrations in excess of 12%. Elevating the
      initial temperature of the vaporizer increased the delivered concentration,
      although this effect was short-lived. Therapeutic concentrations of vapour were
      achieved for all three agents by avoiding bubbling and manipulating the
      'splitting ratio' lever. The Boyle's bottle vaporizer may be used with modern
      anaesthetic agents such as halothane, isoflurane and enflurane. However, the
      limitations of and variations between vaporizers should be borne in mind. An
      agent monitor employed at the patient end of the circuit would be an important
      safety feature.

PMID- 8984870
TI  - The airways and anaesthesia II. Pathophysiology.
AB  - We pointed out in the first of these two articles that the commonest cause of an
      anaesthetic disaster in young healthy patients is a loss of airway patency then a
      failure to intubate occurring unexpectedly in the absence of head or neck
      pathology. Upper airway obstruction is a very common complication of general
      anaesthesia and all anaesthetists must be trained in the management of this
      problem. Less obvious are the changes that can occur in the lower airways which
      can impair gas exchange by increasing ventilation-perfusion mismatch. This
      article is concerned with these pathophysiological changes that occur during
      general anaesthesia.

PMID- 8984871
TI  - Did the use of chloroform by Queen Victoria influence its acceptance in obstetric
      practice?
AB  - Examination of contemporaneous publications suggests that the use of chloroform
      by Queen Victoria in 1853 did not result in the major breakthrough in the
      acceptability of obstetric anaesthesia with which the event has been credited by
      some later writers.

PMID- 8984872
TI  - Serum and urinary myoglobin following an aborted malignant hyperthermia reaction.
AB  - A 13-year-old boy presenting for correction of bat ears was anaesthetised with
      thiopentone and suxamethonium, the administration of which was followed by jaw
      spasm, poor peripheral perfusion (without cyanosis) and marked tachycardia. The
      procedure was abandoned, dantrolene and Ringer lactate IL were given
      intravenously and the patient regained consciousness 1 h later. Levels of serum
      myoglobin, urinary myoglobin and creatine kinase were followed until they
      returned to normal. Despite a peak serum myoglobin of 58.000 micrograms.l-1 and
      peak urinary level of 446,000 micrograms.l-1, no renal impairment occurred.
      Subsequent testing for susceptibility to malignant hyperthermia proved positive
      for the patient and four other members of the family.

PMID- 8984873
TI  - Management of Caesarean delivery in the presence of a large pelvic vascular
      malformation.
AB  - Caesarean section is associated with significant cardiovascular disturbances. We
      present a patient known to have a large pelvic arteriovenous malformation who
      underwent elective Caesarean section. To assist in the monitoring and management
      of the anticipated haemodynamic changes a flow directed pulmonary artery catheter
      with the capacity to allow continuous cardiac output measurement was used.

PMID- 8984874
TI  - Feasibility of day case laparoscopic cholecystectomy in unselected patients.
AB  - The feasibility of day case laparoscopic cholecystectomy was assessed in
      unselected patients using a standard anaesthetic protocol. Postoperative pain and
      nausea were assessed at 6 and 24 h postoperatively (visual analogue scale, range
      0-10). Thirty-two patients were studied (23 female, 9 male, mean age 49.6 years).
      The mean duration of surgery was 68 min. At 6 h after surgery, 10 patients (31%)
      had no pain at rest. For the group as a whole, the median pain score was 3 at
      rest (range 0-6), 4 on movement (0-9), and 5 on coughing (0-9) and eight patients
      (25%) were nauseated. At 24 h, 15 (46.9%) had no pain at rest. For the group as a
      whole, the median pain score was 1 at rest (0-7), 3 (0-6) on movement and 3 on
      coughing (0-9). The same eight patients were nauseated. Ten patients (31.3%) were
      judged fit for discharge at 6 h, and 28 (87.5%) by 24 h. There was no statistical
      difference in mean age or duration of surgery in those judged fit for early
      discharge compared to the study group as a whole. Nausea was an important factor
      in those unfit for discharge at 24 h. Selection criteria might improve these
      figures. From the results of our study, 24 h admission is a more realistic goal
      and will be suitable for most patients requiring laparoscopic cholecystectomy.

PMID- 8984875
TI  - Safety and efficacy of the laryngeal mask airway. A prospective survey of 1400
      children.
AB  - A survey of laryngeal mask airway usage in 1400 infants and children by ten
      trainee anaesthetists was undertaken to provide information about insertion and
      complication rates using the standard insertion technique and a limited range of
      standardised anaesthetic techniques. Placement was successful in 90% (1258/1400)
      at the first attempt, 8% (112/1400) at the second attempt and 2% (29/1400)
      required an alternative technique of insertion. One patient vomited during
      insertion and the procedure was abandoned, but aspiration did not occur. The
      overall problem rate was 11.5% and there were significantly more problems during
      induction of anaesthesia (p < 0.02). Oxygen saturation decreased below 90%
      briefly on 23 occasions (1.7%). The incidence of problems was unrelated to the
      mode of ventilation, or whether isoflurane or total intravenous anaesthesia with
      propofol was used for maintenance. Most problems came with use of the size 1
      laryngeal mask (p < 0.001). The subspecialty with the highest problem rate was
      ear, nose and throat surgery (p < 0.001). There was a significant decrease in
      problems with increasing experience (p < 0.001). There was no major morbidity
      associated with use of the device. We conclude that the laryngeal mask provides a
      safe and effective form of airway management for infants and children in the
      hands of supervised anaesthesia trainees both for spontaneous and controlled
      ventilation using either isoflurane or total intravenous anaesthesia.

PMID- 8984876
TI  - The laryngeal mask airway for thyroid and parathyroid surgery.
AB  - The role of the laryngeal mask airway for thyroid and parathyroid surgery was
      studied in 97 consecutive patients. In 50% the technique combined electrical
      stimulation of the recurrent laryngeal nerve with visualisation of vocal cord
      movement via a fibreoptic bronchoscope. Stimulation was required in 10% to assist
      in identifying recurrent laryngeal nerve position during difficult surgical
      dissection. In the remaining 40% stimulation was used to confirm nerve integrity
      and for teaching purposes. Tracheal intubation was required for seven patients
      but in only two of these was intubation unplanned. The incidence of postoperative
      recurrent laryngeal nerve dysfunction was zero. These data suggest that the
      technique offers a safe alternative in airway management and may provide
      advantages in terms of preservation of recurrent laryngeal nerve function.

PMID- 8984877
TI  - Attitudes of consultant anaesthetists to the Calman proposals: a questionnaire
      survey.
AB  - We undertook a postal survey to determine the views of all consultant
      anaesthetists within the North West (Mersey) Regional Health Authority on the
      Calman proposals for a consultant-based service; replies were received from 110
      (84%). Fifty (45%) indicated that they would not resume emergency residential
      duties, 32 (29%) indicated that they would withdraw from the emergency duty rota,
      12 (11%) said they would withdraw/retire from the NHS and 27 (25%) would change
      hospital under these circumstances. Most consultants had experience in the major
      anaesthetic sub-specialties within the preceding 5 years (obstetrics 67%, ITU
      81%, major trauma 91%). Consequently the need for retraining amongst consultant
      anaesthetists prior to resuming residential emergency duties would be low. When
      questioned about the impact on anaesthetic services, 67 (61%) felt the proposals
      would be detrimental whilst 23 (21%) felt there would be beneficial effects. Most
      consultants remain antagonistic toward the Calman proposals, with a reluctance to
      return to residential duties.

PMID- 8984878
TI  - A comparison between the Macintosh and the McCoy laryngoscope blades.
AB  - The view of the larynx using the Macintosh laryngoscope and the McCoy levering
      laryngoscope was assessed in 177 adult patients. The view with the McCoy blade in
      the neutral position and in the position (neutral or elevated) that gave the
      'best' view were recorded. The McCoy blade in the neutral position was associated
      with a lower incidence of grade 1 views and a higher incidence of grade 2 views
      than the Macintosh blade. There was no difference in the incidence of grade 3
      views. When views for each patient using the different blades were compared, the
      McCoy blade in the neutral position produced a worse view than the Macintosh
      blade (p < 0.0001). The view obtained with the McCoy blade in its 'best' position
      and the Macintosh blade were similar. In the 152 patients in whom the vocal cords
      were seen using the Macintosh blade, the view was worse using the McCoy blade in
      its 'best' position more often than it was better (p = 0.06). In 25 patients, the
      vocal cords could not be seen with the Macintosh blade; in these patients the
      view was better with the McCoy blade (the cords were visible) on 14 occasions and
      worse in one (p = 0.001). We conclude that the McCoy blade in its neutral
      position does not behave identically to the Macintosh blade. The McCoy blade is a
      useful aid to difficult intubation but should not replace the Macintosh blade as
      the first choice laryngoscope.

PMID- 8984879
TI  - A review of 560 Hickman catheter insertions.
AB  - Indwelling, cuffed, tunnelled, central venous (Hickman) catheters are
      increasingly being used for venous access and the administration of chemotherapy
      for oncological patients. This paper reviews the technical problems associated
      with the percutaneous insertion of these catheters and the complications arising
      from their use. Five hundred and sixty catheters were inserted; 31.3% had
      complications at insertion, most commonly precipitation of an arrhythmia (13.9%).
      Arterial puncture occurred in 3.8% and pneumothorax in 1.6%. Catheters remained
      in place for a median period of 91 days. Forty percent of catheters were removed
      electively on completion of treatment; 30.2% required removal because of
      complications, which included sepsis, migration, thrombosis and blockage. Twenty
      percent of patients died with their catheter in place, 8.5% were still in situ
      and 1.6% were removed because of patient non compliance. Sepsis remains the
      commonest, long term complication, with staphylococcus epidermidis being the
      organism isolated most frequently. There were no catheter-related deaths.

PMID- 8984880
TI  - Cricoid pressure--one or two hands?

PMID- 8984881
TI  - Labelling and drug administration error.

PMID- 8984882
TI  - The Mapleson breathing systems.

PMID- 8984883
TI  - Turbulence in the Magill and Lack breathing systems.

PMID- 8984884
TI  - Gelatin solutions.

PMID- 8984886
TI  - The McCoy laryngoscope.

PMID- 8984885
TI  - Digital exploration and the laryngeal mask.

PMID- 8984887
TI  - Another pitfall of pulse oximetry.

PMID- 8984888
TI  - Use of the laryngeal mask airway during oesophago-gastro-duodenoscopy.

PMID- 8984889
TI  - Hyperkalaemia, suxamethonium and malignancy.

PMID- 8984890
TI  - Caesarean section and sleep apnoea syndrome.

PMID- 8984891
TI  - Anaesthesia in a patient with Conradi's disease.

PMID- 8984893
TI  - Antitrust. American Board of Emergency Physicians.

PMID- 8984892
TI  - Characterization of benzodiazepine "combinatorial" chemical libraries by on-line
      immunoaffinity extraction, coupled column HPLC-ion spray mass spectrometry-tandem
      mass spectrometry.
AB  - To characterize combinatorial chemical libraries of small drug compounds, an
      automated column switching system incorporating an immunoaffinity extraction
      (IAE) column and two reversed-phase HPLC columns was coupled to a triple
      quadrupole mass spectrometer. A Protein G column and antibodies to
      benzodiazepines were used to screen library components. A pH change in the mobile
      phase eluted the benzodiazepine-antibody complexes onto a C-18 restricted access
      media (RAM) column, thereby separating the selected benzodiazepines from the
      antibody. In a final step, backflushing the RAM column eluted the benzodiazepines
      onto a C-8 analytical reversed-phase column for separation before detection and
      preliminary structural characterization using ion spray mass spectrometry (MS)
      and tandem mass spectrometry (MS/ MS). A known 19-component library and an
      unknown 20-component library were analyzed. Full-scan IAE/LC/ LC/MS and
      IAE/LC/LC/MS/MS chromatograms suggested the feasibility of this combination of
      techniques, although the antibodies used were not highly specific. Inspection of
      MS/MS spectra of components in the unknown library compared to the MS/MS spectrum
      of a known standard (chlordiazepoxide) identified a subclass of benzodiazepines.
      Productions of the known standard and an unknown benzodiazepine were successively
      captured and fragmented (MSn experiments) using an iontrap mass spectrometer off
      line, which confirmed that the unknown was an analogue of chlordiazepoxide.

PMID- 8984894
TI  - Interleukin-12: Cellular and Molecular Immunology of an Important Regulatory
      Cytokine. Proceedings of a conference. New York City, November 9-12, 1995.

PMID- 8984895
TI  - An efficient expression of human growth hormone (hGH) in the milk of transgenic
      mice using rat beta-casein/hGH fusion genes.
AB  - In order to produce human growth hormone (hGH) in the milk of transgenic mice,
      two expression vectors for hGH differing in their 3' flanking sequences were
      constructed by placing the genomic sequences of hGH gene under the control of the
      rat beta-casein gene promotor. The 3' flanking sequences of the expression
      constructs were derived from either the hGH gene (pBCN1GH) or the rat beta-casein
      gene (pBCN2GH). Transgenic lines bearing pBCN1GH expressed hGH more efficiently
      than those bearing pBCN2GH in the milk (19-5500 micrograms/mL vs 0.7-2
      micrograms/mL). In particular, one of the BCN1GH lines expressed hGH as much as
      5500 +/- 620 micrograms/mL. Northern blot analysis showed that the transgene
      expression was specifically confined to the mammary gland and developmentally
      regulated like the endogenous mouse beta-casein gene in the mammary gland.
      However, a low level of nonmammary expression was also detected with more
      sensitive assay methods. In conclusion, the rat beta-casein/hGH fusion gene could
      direct an efficient production of hGH in a highly tissue-and stage-specific
      manner in the transgenic mice and the 3' flanking sequences of hGH gene had an
      important role for the efficient expression.

PMID- 8984896
TI  - Immobilization of prostaglandin synthetase by hydrophobic adsorption.
AB  - In this article, the immobilization of prostaglandin synthetase on n-alkyl or
      aryl amino-agar beads by hydrophobic adsorption is reported. The effects of
      different hydrophobic groups in the agar beads, pH of buffer, concentration of
      salts on the adsorption of prostaglandin synthetase, and the properties of
      immobilized prostaglandin synthetase were also studied. The results showed that
      20-35 mg of microsome containing PG synthetase (protein content 8-15 mg) could be
      adsorbed on each gram of n-dodecylamino-agar beads after suction drying the gel
      in the buffer of pH 5.5 (containing 0.5 mol/L KCl), 0.1 mol/L citric-phosphate at
      4 degrees C. The remaining immobilized enzyme activity was over 80%. The optimum
      pH of immobilized PG synthetase is 8.0, similar to that of the native enzymes.
      The thermostability of immobilized PG synthetase in the buffer containing 0.5
      mol/L KCl was increased. Immobilized PG synthetase was used as a catalyst of
      synthesis of prostaglandin E1. The preservation of activity after 10 working
      cycles was 86.2%.

PMID- 8984897
TI  - The isolation and purification of diamine oxidase of pea seedlings and pig liver.
AB  - Enzymes have been extensively used in many industries for the last 20 years. They
      are becoming more common because of new areas of application. The limitations of
      applications of enzymes are activity, specificity, stability, and price. Higher
      enzyme activities and less susceptibility of process conditions are desirable.
      Therefore, in some cases, purified enzyme extracts are needed. The purpose of
      this study is the isolation and purification of diamine oxidase (DAO) of pea
      seedlings and pig liver. The relationship between pea seedlings growth rate and
      enzyme activity is established. DAO of pea seedlings and pig liver is prepared by
      way of tissue disruption with homogenization, centrifugation, fractionation with
      ammonium sulfate, precipitation of inert components, column electrophoresis, and
      DEAE-cellulose column chromatography. The specific activity of disrupted pea
      seedlings cells was measured as 0.017 (U/mg protein), and the pig liver DAO
      activity was measured as 0.00037 (U/mg protein). The specific enzyme activity
      from pea seedlings was increased to 6.750 (U/mg protein). On the other hand, the
      specific enzyme activity from pig liver was increased to 0.30 (U/mg protein). The
      final enzyme extract from pea is 400-fold purer than raw material, and the final
      enzyme extract from pig liver is 820-fold purer than raw material.

PMID- 8984898
TI  - Reversible modification of thiol-containing polypeptides with poly (ethylene
      glycol) through formation of mixed disulfide bonds. The case of papaya proteinase
      III.
AB  - Papaya proteinase III (PPIII) was purified, as the S-methylthio derivative from
      the latex of Carica papaya L., by ion-exchange chromatography. Separation of
      reactivable PPIII from the irreversibly oxidized molecular species of this enzyme
      was readily achieved after a selective conversion of the reactivated proteinase
      into the S-monomethoxypoly(ethylene glycol)thio derivative (S-mPEG thio PPIII).
      From this derivative, a PPIII preparation titrating 1 mol of thiol/mol of enzyme
      was regenerated. From the physicochemical properties of S-mPEG thio PPIII that
      were investigated, it is concluded that interactions between the mPEG and the
      PPIII chains occur only to a limited extent. In addition to its usefulness for
      purifying thiol-containing enzymes, the mPEG modification resulting from mixed
      disulfide bond formation may find other practical applications.

PMID- 8984899
TI  - Decolorization of olive mill waste-waters by free and immobilized Phanerochaete
      chrysosporium cultures. Effect of the high-molecular-weight polyphenols.
AB  - This paper describes the decolorization and chemical oxygen demand (COD) removal
      of olive mill waste-waters (OMW) by Phanerochaete chrysosporium grown in agitated
      submerged cultures. When P. chrysosporium was cultivated in the form of pellet,
      no decolorization of crude OMW was observed. Decolorization occurred only after
      removing by ultrafiltration, the high-mol-wt (HM) polyphenolic fraction (> 60
      kDa). The use of high lignin peroxidase (LiP) producing medium yielded the
      highest levels of OMW decolorization and COD removal. In this case, extensive
      depolymerization and subsequent accumulation of phenolics with intermediates
      molecular weight were observed. Furthermore, increasing the concentration of the
      HM fraction decreased the color and COD removals. The decolorizing activity was
      lost when the concentration of the HM fraction reached 25% (v/v). Consequently,
      LiP activity was found to be completely inhibited in the presence of HM fraction,
      but not with the low-mol-wt (LM) polyphenolic fraction (< 8 kDa). The use of P.
      chrysosporium immobilized on polyurethane foam resulted in efficient
      decolorization of crude OMW. Moreover, the addition of an induction medium was
      shown to perform several repeated batch cultures for OMW decolorization and COD
      removal.

PMID- 8984900
TI  - Characterization of a lactate oxidase from a strain of gram negative bacterium
      from soil.
AB  - A lactate oxidase was purified about 36-fold from a newly screened strain KY6 of
      gram negative bacterium from soil to yield a homogeneous protein. The native
      enzyme had a molecular mass of 204 kDa measured by Sephadex G-200 and that of
      subunit on the SDS-PAGE was found to be 45 kDa. The enzyme was optimally active
      at pH 7.7 and showed stability at pH range of 5.7 to 9.5 for 24 h at 4 degrees C.
      The optimum temperature was 70 degrees C and the enzyme activity was stable for
      10 min up to 45 degrees C. The half-life of the enzyme activity was about 10 min
      at 55 degrees C. The best substrate of the enzyme was D-lactate and Km value for
      D-lactate was 0.14 mM. The Km value for DL-lactate was 0.20 mM. Substrate
      inhibition of the enzyme was observed at higher concentrations than 20 mM of DL
      lactate and 10 mM of D-lactate.

PMID- 8984901
TI  - Development of a generalized phenomenological model describing the kinetics of
      the enzymatic hydrolysis of NaOH-treated pine wood.
AB  - Pinus pinaster wood samples were treated during 3 h with alkaline solutions
      (containing 1, 5.5, or 10 weight percent NaOH) at 100, 115, or 130 degrees C
      using liquor/wood ratios of 6, 8, or 10 g/g. The solid residues obtained in
      treatments were used as substrates for enzymatic hydrolysis. In the hydrolysis
      assays, the reaction time (in the range 0-48 h) was considered as an operational
      variable. The cellulose conversion achieved at the end of assays were highest for
      samples pretreated at high temperature and high alkali concentration using low
      liquor/wood ratios. The experimental results obtained in each hydrolysis trial
      were fitted to an empirical model based on the assumption that the cellulose
      contained in substrates was composed by two fractions having different
      susceptibility to hydrolysis. The kinetic parameters obtained for the various
      experiments performed were correlated with the operational variables by means of
      empirical, statistically significant equations, which provided a generalized
      interpretation of the process.

PMID- 8984902
TI  - Purification of a marine bacterial glucose dehydrogenase from Cytophaga
      marinoflava and its application for measurement of 1,5-anhydro-D-glucitol.
AB  - A novel glucose dehydrogenase (GDH) from a marine bacterium Cytophaga marinoflava
      IFO 14170 was isolated from its membrane fraction. This GDH catalyzes the
      oxidation of a hydroxy group of glucose, but does not react in its C-1 position.
      This enzyme is composed of a single peptide with a mol wt of 67,000. The GDH can
      react under high salinity. The optimum pH is around 8.0, showing typical property
      of marine bacterial enzymes. Using this novel enzyme, and enzymatic determination
      of 1,5-anhydro-D-glucitol (1,5AG) utilizing 2,6-dichrolophenolindophenol (DCIP)
      and phenazine methosulfate (PMS) as electron mediators was carried out. A good
      linear correlation was observed from 0.5 mM to 4 mM of 1,5AG.

PMID- 8984903
TI  - A novel synthesis method for cyclodextrins from maltose in water-organic solvent
      systems.
AB  - A novel enzymatic synthesis method of cyclodextrin (CD) from low-mol-wt maltose
      using cyclomaltodextrin glucanotransferase (CGTase) from Bacillus macerans has
      been developed in various water-organic solvent systems. A beta-CD was
      synthesized in a two-phase system consisting of water and cyclohexane. However,
      no CDs could be synthesized in an aqueous buffer solution. A maximal yield of
      beta-CD has been obtained at a cyclohexane content volume of 44%. This synthesis
      has been obtained only at low temperatures, i.e., 7 degrees C, and did not take
      place at 50 degrees C. In addition, various organic solvents have been used for
      the enzymatic synthesis of CD from maltose. Consequently, beta-CD could be
      synthesized in various water-organic solvent systems, e.g., cyclohexane, benzene,
      xylene, and chloroform, but no enzymatic reaction occurred using aliphatic n
      hydrocarbon solvents such as hexane, dodecane, and hexadecane. Furthermore, alpha
      and beta-CD could be synthesized in water mixture solutions using organic
      solvents having an alcoholic group (e.g., ethanol, propanol, butanol, and
      pentanol) in a wide range of the reaction temperatures, typically 7-50 degrees C.
      In this temperature range, alpha- and beta-CD were also formed and the maximal
      yield from maltose to beta-CD of approx 13% was reached in 60 h.

PMID- 8984905
TI  - Immobilized chymotrypsin on reversibly precipitable polymerized liposome.
AB  - A polymerized liposome (PLS) was prepared using a synthesized
      phosphatidylethanolamine with a diacetylene moiety that showed a reversibly
      precipitable property on addition and removal of salt. To prepare a soluble
      insoluble immobilized enzyme, chymotrypsin was covalently immobilized on the
      outer surface of the PLS. The carbodiimide method was employed for the enzyme
      immobilization. Coupling was rapid and nearly complete at a weight ratio of
      enzyme to the PLS of < 0.12. The immobilized enzyme showed favorable activity
      yields for both low- and high-mol-wt substrates, i.e., 90 +/- 9% for N-benzoyl-L
      tyrosine ethyl ester and 59 +/- 5% for casein up to an enzyme coupling density of
      0.38 g/g-PLS. The immobilized enzyme was reusable and more stable at high
      temperature and long-term incubation than the native enzyme.

PMID- 8984906
TI  - Synthesis of alanine and leucine by reductive amination of 2-oxoic acid with
      combination of hydrogenase and dehydrogenase.
AB  - Alanine synthesis by reductive amination of pyruvate was performed by the
      combination of NADH regeneration system and alanine dehydrogenase (AlaDH). The
      conversion of pyruvate to alanine was 99% after 1 h. Leucine synthesis was also
      carried out by the combination of NADH regeneration system and leucine
      dehydrogenase (LeuDH). The conversion of 4-methyl-2-oxovalerate to leucine was
      60% after 1.5 h.

PMID- 8984904
TI  - Milk-clotting activity of cucumisin, a plant serine protease from melon fruit.
AB  - Cucumisin (EC 3.4.21.25) isolated from prince melon fruit is a plant serine
      protease. Its milk-clotting activity was compared with plant cysteine proteases
      such as papain (EC 3.4.22.2) and ficain (EC 3.4.22.3). Cucumisin was more stable
      than papain under the condition of pH 7.1, 37 degrees C for 24 h. The milk
      clotting activity of cucumisin was the same to that of papain and was half value
      of that of ficain.

PMID- 8984907
TI  - Hemolytic activity reevaluation of putative nonpathogenic Listeria monocytogenes
      strains.
AB  - Identification of 12 strains originally characterized as nonpathogenic Listeria
      monocytogenes was reassured following the evaluation of their hemolytic
      capability with a newly developed horse blood agar plate. Seven of the strains
      were observed consistently to be hemolytic and confirmed as L. monocytogenes with
      the use of two commercial systems: the Gene-Trak L. monocytogenes-specific
      colorimetric DNA hybridization assay and the API Listeria system. Except for one
      strain that formed typical smooth colonies, these hemolytic strains formed rough
      colonies on a selective medium, lithium chloride-ceftazidime agar. The rest of
      the strains were nonhemolytic and did not hybridize with the DNA probe; they were
      identified as Listeria innocua on the basis of their API Listeria system
      biochemical profile. All but one of these nonhemolytic strains formed smooth
      colonies on lithium chloride-ceftazidime agar.

PMID- 8984908
TI  - Evaluation and management of precocious puberty.

PMID- 8984909
TI  - Mesenteric cysts.

PMID- 8984910
TI  - Whole body protein metabolism in children with cancer.
AB  - Whole body protein synthesis and catabolism were measured using the [ring
      2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32
      paediatric patients with cancer at different stages of treatment. Rates of
      synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1
      13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8)
      (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two
      tracer techniques give similar results in this study population. Comparison of
      these values with results previously reported for groups of control children
      using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28
      g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates
      of synthesis and catabolism were higher in cancer patients than in controls. Thus
      whole body protein turnover is increased in children under treatment for cancer.
      Other indices of metabolism such as plasma amino acids and intermediary
      metabolites were also measured and showed that, although subjects were in
      isotopic steady state, there were significant metabolic changes during the course
      of the primed constant infusions used to measure protein turnover.

PMID- 8984911
TI  - Metabolic rate of sleeping infants.
AB  - AIM: To measure the sleeping metabolic rate (SMR) of healthy infants in the first
      year of life. METHODS: The SMR was measured on 73 infants aged 1 to 12 months in
      a special nursery using indirect calorimetry. One hundred satisfactory
      observations were made. The room air and radiative temperatures, humidity, and
      amount of insulation were measured. Parents chose the clothing and bedding that
      they judged their infant needed. RESULTS: The mean (SD) SMR was 2.4 (0.4) watts
      (W)/kg or 45 (10) W/m2. The mean SMR of infants aged 1-2 months was 38 compared
      with 44 W/m2 in infants of 8-12 months; the difference was not significant. There
      were no obvious differences in SMR between boys and girls. But there were wide
      differences in SMR between apparently similar infants, range 1.4 to 3.5 W/kg.
      Most parents selected insulation between 1 and 3 togs, and this was weakly
      negatively correlated with air temperature. CONCLUSION: These wide variations in
      SMR mean that it is impossible to give specific guidelines on the amount of
      clothing and bedding a particular infant will need for thermal comfort in a given
      room temperature.

PMID- 8984912
TI  - Individual variation in sleeping metabolic rates in infants.
AB  - AIM: To measure the variation in sleeping metabolic rate (SMR) of healthy infants
      in the first year of life. METHODS: Attempts were made to measure SMR in the home
      of one group of infants at monthly intervals over the first year of life and of
      another group in the 1 to 12 age range, over three consecutive days. Sixty one
      infants were recruited and 181 measurements made. In 11 infants six or more
      satisfactory measurements were made a monthly intervals and in another 11
      infants, three consecutive daily measurements were obtained. Parents chose the
      clothing and bedding that they judged their infant needed to fall asleep. The
      room air and radiative temperatures, humidity, and amount of insulation were
      recorded. RESULTS: The mean (SD) SMR was 2.4 (0.4) watts (W)/kg or 45 (10) W/m2.
      The rate was the same for infants in the age groups 0.25, 0.5, 0.75, and 1 years;
      individual infants did not show a systematic change with age. There was wide
      variation. Ninety eight per cent of infants had a SMR between 1.8 and 3.1 W/kg.
      The mean SMR for the infants measured on three consecutive days varied from 1.7
      to 3.1 W/kg, and SMR varied within infants, from 0.06 to 0.86 W/kg. The variation
      within six to 11 measurements on infants over the first year of life ranged from
      0.38 to 1.05 W/kg. CONCLUSION: Infants in the first year of life exhibit wide
      variations in SMR from day to day and from month to month. As the range is wide,
      guidance on clothing and bedding for thermal comfort can be given only in broad
      terms.

PMID- 8984913
TI  - Final height in central precocious puberty after long term treatment with a slow
      release GnRH agonist.
AB  - OBJECTIVE: To study the resumption of puberty and the final height achieved in
      children with central precocious puberty (CPP) treated with the GnRH agonist
      triptorelin. PATIENTS: 31 girls and five boys with CPP who were treated with
      triptorelin 3.75 mg intramuscularly every four weeks. Girls were treated for a
      mean (SD) of 3.4 (1.0) years and were followed up for 4.0 (1.2) years after the
      treatment was stopped. RESULTS: The rate of bone maturation decreased during
      treatment and the predicted adult height increased from 158.2 (7.4) cm to 163.9
      (7.5) cm at the end of treatment (p < 0.001). When treatment was stopped bone
      maturation accelerated, resulting in a final height of 161.6 (7.0) cm, which was
      higher than the predicted adult height at the start of treatment (p < 0.001).
      Height at the start of treatment was the most important factor positively
      influencing final height (r = 0.75, p < 0.001). Bone age at cessation of
      treatment negatively influenced final height (r = -0.52, p = 0.03). A negative
      correlation between bone age and height increment after discontinuation of
      treatment was observed (r = -0.85, p = 0.001). Residual growth capacity was
      optimal when bone age on cessation of treatment was 12 to 12.5 years. Body mass
      index increased during treatment and remained high on cessation. At final height,
      the ratio of sitting height to subischial leg length was normal. Menarche
      occurred at 12.3 (1.1) years, and at a median (range) of 1.1 (0.4 to 2.6) years
      after treatment was stopped. The ovaries were normal on pelvic ultrasonography.
      CONCLUSIONS: Treatment of CPP with triptorelin increases final height, with
      normal body proportions, and seems to increase body mass index. The best results
      were achieved in girls who were taller at the start of treatment. Puberty was
      resumed after treatment, without the occurrence of polycystic ovaries.

PMID- 8984915
TI  - Interview data on severe behavioural eating difficulties in young children.
AB  - Interview data from parents of 201 children under age 7 years with severe feeding
      and eating difficulties were analysed to describe features in the child's and
      parents' experiences that may have contributed to the development of the eating
      problem. Prematurity and low birth weight, distress during feeding in the first
      six months of life, and regular or frequent vomiting were common findings in the
      histories of the children. Aversive experiences during feeding may be the basis
      for early childhood eating difficulties.

PMID- 8984914
TI  - Combined diphtheria, tetanus, pertussis, and Haemophilus influenzae type b
      vaccines for primary immunisation.
AB  - A total of 146 infants were immunised at ages 2, 3, and 4 months with a combined
      diphtheria, tetanus, pertussis (DTP)--Haemophilus influenzae type b (Hib) tetanus
      toxoid conjugate (PRP-T) vaccine (Pasteur Merieux) to assess the antibody
      response and adverse events associated with immunisation. Adverse events,
      including fever, were recorded by parents in a diary for three days following
      each injection. Blood was taken before the first immunisation and four weeks
      after the third immunisation to assess antibody response. Data were compared with
      those from historical controls who had received DTP and PRP-T vaccines by
      separate injection. The combined vaccine was well tolerated. Rates of local and
      general reactions were similar to those reported for infants immunised by
      separate injection. All infants achieved protective antibody titres (> 0.01
      IU/ml) for diphtheria and tetanus; 98% acquired Hib (PRP) antibody > 0.15
      microgram/ml and 82.5% > 1.0 microgram/ml. Pertussis antibody titres (pertussis
      toxin, filamentous haemagglutinin, total agglutinins, and agglutinins 2 and 3)
      showed appreciable rise following immunisation. DTP and PRP-T vaccines provide
      similar antibody responses and adverse effects whether mixed in the same syringe
      or administered by separate injection. The vaccines could be combined for use in
      the United Kingdom primary immunisation schedule.

PMID- 8984916
TI  - Parents' and children's reactions to taking blood in a nutrition survey.
AB  - OBJECTIVE: To assess the reactions of parents and their children to the request
      for a blood sample and an attempt to take blood. METHODS: 1859 children aged 1.5
      4.5 years took part in a national survey of diet and nutrition. A retrospective
      inquiry of the parents' and children's reported reactions was carried out six to
      18 months later by postal questionnaire sent only to the 1157 who had given
      consent for an attempt to take blood. RESULTS: 866 questionnaires were returned;
      790 were from parents of children in whom an attempt to take blood had been
      successful. Thirteen per cent said that their child had given blood previously.
      About 30% discussed the request with the family doctor or nurse. Some 90% said
      that they were given enough information and that the phlebotomist was
      sympathetic. Attempting to take blood caused upset in over 50%, which, in most,
      lasted for less than five minutes. A substantial minority were upset for up to 30
      minutes and a few much longer. Bruising or bleeding occurred in 20-27%. Degree
      and duration of upset were both adversely associated with a failed attempt to
      obtain blood. CONCLUSION: The majority of preschool children experienced no more
      than a little upset of short duration after an attempt to take blood, but a
      substantial minority exhibited a greater degree of upset. These responses should
      be taken into account when assessing the benefits and risks of the procedure. The
      best equipment and expertise should be employed for taking blood as successful
      attempts are less upsetting.

PMID- 8984917
TI  - Effects of inhaled steroid treatment on serum eosinophilic cationic protein (ECP)
      and low affinity receptor for IgE (Fc epsilon RII/sCD23) in childhood bronchial
      asthma.
AB  - Serum eosinophilic cationic protein (ECP) and soluble low affinity receptor for
      IgE (Fc epsilon RII/sCD23) concentrations were measured in relation to symptom
      medication scores, pulmonary function, and total IgE levels in 27 chronic
      allergic asthmatic children (17 boys, 10 girls), mean age 10.8 years, before and
      at the end of a three month inhaled corticosteroid (budesonide) treatment period.
      Serum ECP and sCD23 concentrations were also measured in age matched non
      asthmatic controls with allergic rhinitis. All asthma patients had significantly
      higher serum ECP and sCD23 than the controls, whereas the mean serum IgE was not
      different. No correlation between total IgE concentrations and serum sCD23 could
      be detected in either group. At the end of the treatment period, symptom
      medication scores and pulmonary function improved. Serum ECP and sCD23
      concentrations were reduced; however, total IgE values did not change
      significantly. A significant relation was found between the improvement of
      symptom-medication scores and fall in both sCD23 and ECP concentrations. Although
      there was a significant correlation of pulmonary function values with serum ECP,
      no such relation was observed for sCD23. It appears that serum sCD23 and ECP
      concentrations could be good disease markers, particularly in asthma. Monitoring
      of serum inflammation markers, especially ECP, may be useful in the follow up of
      asthmatic children on anti-inflammatory treatment.

PMID- 8984918
TI  - Reduced upper airway nitric oxide in cystic fibrosis.
AB  - Nitric oxide (NO) produced within the respiratory tract is detectable in exhaled
      and nasal air. Its synthesis may be induced by inflammatory cytokines and reduced
      by glucocorticoids. Increased concentrations have been found in asthma and
      bronchiectasis. In this study, NO concentrations were determined in 63 children
      with cystic fibrosis, of whom 13 were on inhaled steroids (mean age 13.3 years)
      and 50 were not (mean age 12.3 years); 57 normal children (mean age 12.2 years)
      were also studied. NO was measured by chemiluminescence analyser, exhaled NO
      following a relaxed vital capacity manoeuvre, and nasal NO with the breath held
      following a full inspiration. Mean concentration of exhaled NO in cystic fibrosis
      patients (no steroids) was 4.7 parts per billion (ppb) (95% confidence interval
      (CI) 4.0 to 5.3); this did not differ from values in normal children (mean 4.8
      ppb, 95% CI 3.8 to 5.8) or in cystic fibrosis patients on inhaled steroids (mean
      3.6 ppb, 95% CI 2.5 to 4.8). Nasal concentrations were significantly lower in
      cystic fibrosis patients, with or without inhaled steroids, than in normal
      children (cystic fibrosis, no inhaled steroids: 460 ppb, 95% CI 399 to 520;
      cystic fibrosis, inhaled steroids: 522 ppb, 95% CI 313 to 730, v normal children:
      1024 ppb, 95% CI 896 to 1152, p < 0.0001). Considering the inflammatory nature of
      cystic fibrosis, it is surprising exhaled NO levels were not increased, but this
      may have been due to alteration in NO diffusion through thick mucus. The low
      nasal NO concentrations, which are probably the result of impaired flow from the
      paranasal sinuses, may contribute to the recurrent respiratory infections typical
      of cystic fibrosis.

PMID- 8984919
TI  - Exhaled nitric oxide in paediatric asthma and cystic fibrosis.
AB  - Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced
      in the upper airways, whereas basal NO excretion in the lower airways is low.
      Children with Kartagener's syndrome have an almost total lack of NO in nasally
      derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO
      excretion was measured in the nasal cavity and in orally exhaled air in 19
      healthy children, in 36 age matched subjects with asthma, and in eight children
      with cystic fibrosis. NO levels in orally exhaled air were similar in controls
      and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per
      billion (ppb), but were increased in asthmatic children who were untreated or
      were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb).
      Nasal NO levels were reduced by about 70% in children with cystic fibrosis
      compared to controls and asthmatics. Measurements of airway NO release in
      different parts of the airways may be useful in non-invasive diagnosis and
      monitoring of inflammatory airway diseases.

PMID- 8984920
TI  - Height and weight achievement in cleft lip and palate.
AB  - Growth was studied in 83 children with cleft lip and/or palate aged 0-4 years
      attending a specialist regional centre. Information was collected by a personal
      interview, postal questionnaire, and record review. The group as a whole grew
      relatively poorly in early infancy but subsequently recovered, attaining both
      expected weight and height by last follow up at age 25.5 months (range 3 to 47).
      However, the group proved heterogeneous, with children with isolated clefts of
      the secondary palate showing the most abnormal growth. Children with underlying
      syndromes were significantly more likely to be short at follow up, while type or
      severity of cleft was not significantly related to follow up height. Therefore,
      while cleft palate was associated with significant growth faltering in early
      infancy, rapid recovery took place following surgical repair and appears to have
      resulted in no residual growth deficit.

PMID- 8984921
TI  - Growth of the uterus.
AB  - BACKGROUND: The pattern of growth of the uterus was examined by ultrasound
      examinations of 358 girls who attended a paediatric endocrine outpatient
      department but were shown not to have any endocrine defect. METHOD: The uterus
      was measured in length and width at the cervix and at the fundus (cm).
      Endometrial thickness was measured (mm). Scans were divided by Tanner breast
      stage and the dimensions compared by one way analysis of variance (ANOVA, with
      the Student Newman Keuls post hoc test). RESULTS: There was an increase in
      uterine length, diameter of the fundus, and endometrial thickness at each breast
      stage from 1 to 5 (ANOVA, p < 0.05), and in the diameter of the cervix with each
      breast stage from 1 to 4 (ANOVA, p < 0.05). The ratio of the fundus to the cervix
      increased from 0.95 to 1.29 between breast stages 1 and 4. CONCLUSION: The onset
      of puberty is marked by an increase in the dimensions of the uterus and in
      endometrial thickness, but also by a change in the shape of the uterus from a
      tubular to a pear shaped organ.

PMID- 8984923
TI  - Ultrasound compared with clinical examination in infantile hypertrophic pyloric
      stenosis.
AB  - OBJECTIVES: To assess the accuracy of clinical examination as compared with
      ultrasound imaging in the diagnosis of infantile hypertrophic pyloric stenosis.
      Duration of hospital stay, time between admission and surgery, and financial
      implications were also considered. DESIGN: A prospective study of patients
      referred to the surgical team with a possible diagnosis of pyloric stenosis from
      May 1993 to January 1995. SETTING: Neonatal and paediatric surgical wards and
      imaging department of a paediatric teaching hospital. SUBJECTS: 116 patients
      referred to the surgical team with a possible diagnosis of pyloric stenosis.
      RESULTS: 75 patients in this study had pyloric stenosis (64.6%). Clinical
      examination had a sensitivity of 72%, specificity of 97%, with a positive and
      negative predictive value of 98% and 61% respectively. There were 16 diagnostic
      errors (one false positive and 15 false negative). Ultrasound imaging had a
      sensitivity of 97%, specificity of 100%, with a positive and negative predictive
      value of 100% and 98% respectively. There was one diagnostic error (one false
      negative). Eight patients required repeat scans for confirmation of the
      diagnosis. On review of the initial scans in these patients, seven were noted to
      have inaccurate measurements due to poor technique. The average time between
      repeated scans was 28.2 hours. Ultrasound imaging cost 13.90 pounds per scan and
      initiated a change in management only in the clinically false negative group at a
      cost of 52 pounds per patient. The average duration of hospital stay was 3.1 days
      and the mean time between admission and surgery was 19.2 hours. The total cost
      for treatment of a patient with pyloric stenosis was 1602 pounds. CONCLUSION:
      Ultrasound imaging should be reserved for those cases where clinical examination
      is negative and should be carried out by sonographers who see enough cases to
      maintain their expertise.

PMID- 8984922
TI  - Possible aetiology of haemorrhagic shock and encephalopathy syndrome in the Negev
      area of Israel.
AB  - A retrospective study was performed for all patients diagnosed with haemorrhagic
      shock and encephalopathy syndrome (HSES) over an 11 year period (1984-94). Soroka
      University Medical Centre is the only medical facility in the southern Negev
      region of Israel serving a population of about 400,000 residents, consisting
      primarily of two ethnic populations, Jews and Bedouins. Twenty patients, 17
      Bedouin and three Jews, were diagnosed with HSES. The annual incidence of HSES
      for infants under the age of 1 year was 5:10,000 for Bedouins and 0.6:10,000 for
      Jews. Patients ranged in age from 6 to 32 weeks and arrived at the hospital late
      at night or early morning (2:00 am to 11:00 am), during the winter or early
      spring (November to April). All were healthy before admission, with short
      prodromal symptoms of upper respiratory tract or gastrointestinal infection noted
      in 10 cases. Most infants had markedly high body temperature on arrival. A
      history of overwrapping and/or excessive heating was obtained in four of 20
      infants. Bacteriological and virological cultures were negative in all infants.
      One infant died and neurological sequelae were observed in all survivors. The
      high prevalence of hyperpyrexia during sleep in the presence of negative
      microbiological results with no evidence of excessive heating, and the high
      incidence of HSES among a closed and culturally isolated society known to have a
      high incidence of congenital malformations, may support previous assumptions that
      HSES results from hyperpyrexia, originating in most cases from a 'physiological'
      heat induced trigger, which starts and peaks during the night in previously
      healthy infants who are genetically susceptible.

PMID- 8984924
TI  - Early acute otitis media and siblings' attendance at nursery.
AB  - To assess the relation between early acute otitis media and exposure to
      respiratory pathogens mediated by siblings and other children, a prospective
      cohort of 3754 Norwegian children born in 1992-3 was followed up from birth to 12
      months. Of these, 25% had one or more episodes of acute otitis media during the
      first year. Results from multiple logistic regression analysis adjusted for
      confounding showed that siblings' attendance at daycare is the most important
      risk factor for early acute otitis media (adjusted odds ratio, ORadj = 1.9). The
      total number of children in the daycare setting is another determinant for early
      acute otitis media (ORadj = 2.0 in groups of four or more other children and
      ORadj = 1.3 in groups of one to three other children, as compared to those who
      are cared for alone). Having siblings in daycare outside the home and the number
      of children in the daycare setting are the most important determinants for early
      acute otitis media.

PMID- 8984925
TI  - Antiphospholipid syndrome presenting as episodic limb ischaemia.
AB  - A child presented with ischaemic episodes of his left leg from the age of 2
      months. He was found to have raised anticardiolipin antibodies so was started on
      low dose aspirin. At a three year follow up he was asymptomatic with a normal
      anticardiolipin antibody level while taking aspirin daily, probably for life.

PMID- 8984926
TI  - The laryngeal mask airway in fibreoptic bronchoscopy.
AB  - A large series of patients is reported in whom the laryngeal mask airway was used
      to perform fibreoptic bronchoscopy. It allows direct visualisation of the airways
      during spontaneous respiration. It has enabled bronchoalveolar lavage and
      bronchography to be performed in children as young as 6 months and transbronchial
      biopsies in children as young as 4 years.

PMID- 8984929
TI  - Misdiagnosis of pancreatitis during valproate treatment in gastro-oesophageal
      reflux.

PMID- 8984927
TI  - Advances in genetics.

PMID- 8984928
TI  - Management of growth failure in Crohn's disease.

PMID- 8984930
TI  - Prevalence of antidelta in Turkish children with chronic hepatitis B infection.

PMID- 8984932
TI  - Microscopic analysis of synovial fluid--the perfect diagnostic test?

PMID- 8984931
TI  - Vasculitis associated with levamisole and circulating autoantibodies.

PMID- 8984933
TI  - Surfing for rheumatologists--a guide to rheumatology resources on the Worldwide
      Web.

PMID- 8984936
TI  - Antinuclear antibody determination in a routine laboratory.
AB  - Pitfalls in the method for demonstrating antinuclear antibodies (ANA) by the
      indirect immunofluorescence technique are described and the use of international
      standard preparations outlined. Determination of the optimal border dilution
      dividing positive from negative results is discussed. Each laboratory is a unique
      setting; it must define its own method, which should rarely be changed. One
      should not rely on copying methods from other laboratories or commercial firms,
      but the reproducibility of the nuclear substrate, the conjugate, and other
      variables should be controlled daily by the use of a control serum which has been
      related to the WHO standard preparation for ANA of the homogeneous type. Since
      many sera contain mixtures of different ANA, the results of routine tests are
      best expressed in titres or expressions of the intensity of fluorescence. The ANA
      test using the immunofluorescence technique should be used as a screening method
      for other tests allowing a more defined interpretation of the ANA. Each
      laboratory should individually determine the border between positive and negative
      results. Therefore about 200 sera from local healthy controls equally distributed
      over sex and age, and 100 sera from local patients with definite SLE should be
      tested. Since the local clinicians should become acquainted with this border it
      should rarely be changed. Finally each laboratory should participate regularly in
      national and international quality control rounds, where sera known to be
      difficult to interpret are tested. The judgment of the organisers of these rounds
      should stimulate improvements in the participating laboratories.

PMID- 8984935
TI  - Novel pharmacological strategies for analgesia.

PMID- 8984934
TI  - Current and potential future drug treatments for osteoporosis.
AB  - There has been a major interest in the drug treatment of osteoporosis and an
      increase in the number of drugs available in most countries. The ideal drug (one
      which increases or restores bone density and trabecular connectivity) is still
      not available. However, in patients with relatively preserved trabecular
      connectivity and moderately reduced bone density, several agents have shown
      substantial clinical benefit. Oestrogens are still the mainstay of drug
      treatment, but the risks of breast cancer versus the cardiovascular and skeletal
      benefits with long term use have to be assessed in the individual. Newer tissue
      specific oestrogens show some promise in this respect. The bisphosphonates and
      possibly fluoride are likely to be the major alternatives to oestrogens in the
      medium term. The newer bisphosphonates, alendronate and in the future
      risedronate, are likely to supersede etidronate. Calcitriol probably has a
      limited role, confined to those patients in whom HRT or bisphosphonates are not
      appropriate. Calcium supplementation, or an increase in dietary intake if
      deficient, irrespective of which agent is used, is also of benefit. In older
      patients there is considerable support for using a combination of calcium and
      vitamin D. Whether combination treatment, for example oestrogens,
      bisphosphonates, and calcium together, will result in greater efficacy remains to
      be conclusively shown, but may be an attractive option in younger patients with
      higher bone turnover. Apart from fluoride, bone formation stimulators are
      unlikely to have a major role until the next century, although it may be possible
      to use growth factors as part of an ADFR regimen (A = activate remodelling, D =
      depress resorption, F = free formation, and R = repeat). This is still an
      important theoretical approach and needs further work with newer agents to see if
      increased efficacy can be found. In addition sequential treatment may be
      necessary in view of the limited time periods over which particular agents, such
      as intermittent fluoride (four years), have been examined, and this will have to
      be individually tailored. Other approaches include trying to increase peak bone
      mineral density, although influencing the young to prevent a disease that may not
      manifest itself for half a century is daunting.

PMID- 8984937
TI  - An uncommon cause of finger drop in a patient with rheumatoid arthritis.

PMID- 8984938
TI  - Purine enzyme activities in recent onset rheumatoid arthritis: are there
      differences between patients and healthy controls?
AB  - OBJECTIVE: Purine enzyme activities may predict the effectiveness of azathioprine
      treatment and be associated with increased deaths from infectious diseases. In
      rheumatoid arthritis, patients show variable responses to azathioprine and a
      higher percentage of death is caused by infections. The aim of the study was to
      investigate possible rheumatoid arthritis associated abnormalities of purine
      enzyme activities by measuring several of these enzymes in patients with recent
      onset rheumatoid arthritis before treatment with disease modifying antirheumatic
      drugs or prednisone. METHODS: 23 patients with recent onset rheumatoid arthritis
      and 28 healthy controls were studied. Activities of the enzymes 5'-nucleotidase,
      purine nucleoside phosphorylase (PNP), hypoxanthine guanine
      phosphoribosyltransferase (HGPRT), and thiopurine methyltransferase (TPMT) were
      measured. Assessment of disease activity and blood sampling for routine
      measurements and HLA typing were done simultaneously. RESULTS: Purine enzyme
      activities did not differ between patients and healthy controls. Enzyme
      activities had no significant relations with indices of disease activity or
      rheumatoid factor titre or with the rheumatoid arthritis associated HLA types.
      Activity of 5'nucleotidase decreased with age (P < or = 0.05) and was lower by
      about 27% (P = 0.007) in males than in females. CONCLUSIONS: In rheumatoid
      arthritis patients, neither the variability in azathioprine effectiveness nor the
      increased death rate from infections can be explained by pre-existing
      abnormalities in the activities of the purine enzymes 5'-nucleotidase, PNP,
      HGPRT, or TPMT at an early stage of the disease, before disease modifying
      antirheumatic drugs or prednisone treatment. Besides adjustment for age, results
      of studies involving purine 5' nucleotidase activity should also be adjusted for
      sex.

PMID- 8984939
TI  - Effect of recombinant human erythropoietin on anaemia and disease activity in
      patients with rheumatoid arthritis and anaemia of chronic disease: a randomised
      placebo controlled double blind 52 weeks clinical trial.
AB  - OBJECTIVE: To study whether recombinant human erythropoietin (r-hu-Epo) improves
      anaemia and reduces disease activity in patients with rheumatoid arthritis and
      anaemia of chronic disease (ACD). METHODS: A 52 week placebo controlled
      randomised double blind trial with r-hu-Epo was performed in 70 patients with
      active rheumatoid arthritis and ACD. Thirty four patients were treated with 240 U
      kg-1 r-hu-Epo subcutaneously, initially three doses weekly, while 36 patients
      received placebo. RESULTS: A significant increase of haemoglobin from a median of
      112 to 135 g litre-1 occurred in the Epo group within six weeks and could be
      sustained with reduced doses (median 240 U kg-1 once weekly). Sustained benefit
      compared to placebo was also apparent by six weeks for disease activity, as
      indicated by the Paulus 20% response rate. Of patients in the Epo group, 32%
      eventually showed a Paulus 20% response, compared to 8% of the placebo group (P =
      0.016). Significant differences in favour of the Epo group were also observed in
      the secondary disease activity measures Ritchie index, number of swollen joints,
      pain score, ESR, and patients' global assessment of disease activity. C reactive
      protein concentrations did not change significantly. CONCLUSIONS: Treatment of
      ACD in rheumatoid arthritis with r-hu-Epo is effective in restoring normal
      haemoglobin levels and also exerts a beneficial effect on disease activity.

PMID- 8984940
TI  - Increased circulating nerve growth factor is directly correlated with disease
      activity in juvenile chronic arthritis.
AB  - OBJECTIVE: To determine the circulating serum concentrations of nerve growth
      factor (NGF) and compare them with indices of disease activity in juvenile
      chronic arthritis. METHODS: NGF concentrations were evaluated with a two site
      immunoenzymatic assay (ELISA), in 17 children with systemic, 39 with
      polyarticular, and 24 with pauciarticular onset juvenile chronic arthritis. Each
      subset was divided according to different variables, appropriate to each subset,
      reflecting active and inactive disease. RESULTS: NGF concentrations were
      significantly higher in children with systemic [254 (SD 256.1) pg ml-1; P <
      0.001], polyarticular [165.2 (300.8) pg ml-1; P < 0.05], and pauciarticular
      [106.8 (111.8) pg ml-1; P < 0.005] onset juvenile chronic arthritis than in
      controls. In all subsets, NGF concentrations were higher in the active than in
      the inactive phase of the disease. A significant direct correlation between NGF
      concentrations and erythrocyte sedimentation rate was found both in the systemic
      and in the polyarticular onset juvenile chronic arthritis. CONCLUSIONS: The
      increase in NGF concentrations in all juvenile chronic arthritis subsets and the
      correlation with disease activity suggest that NGF may take an active part in
      joint inflammation.

PMID- 8984941
TI  - Fractal signature analysis measures cancellous bone organisation in
      macroradiographs of patients with knee osteoarthritis.
AB  - OBJECTIVE: To determine whether fractal signature analysis (FSA) of digitised
      macroradiographs of knees quantifies alterations in trabecular structure in the
      tibial cancellous bone of osteoarthritic patients with either early or definite
      joint space narrowing compared with non-arthritic subjects. METHODS: 90
      osteoarthritic knees had macroradiographs at x5 magnification. Joint space width
      and FSA of horizontal and vertical trabecular organisation in the tibial
      subarticular cancellous bone were measured in the medial and lateral tibio
      femoral compartments and compared to reference values obtained from the knees of
      14 healthy non-arthritic volunteers, and to the subject's age and weight.
      RESULTS: Compared to the non-arthritic joints, FSA of the trabecular structure of
      the medial diseased compartment of the tibia was significantly different and
      correlated with the degree of joint space narrowing (P < 0.003); FSA of
      horizontal trabecular structures decreased (P < 0.001) in knees with early
      osteoarthritis (joint space > 3 mm) and vertical trabecular FSA increased in
      knees with marked joint space narrowing (joint space < 3 mm). In the lateral
      compartment of the tibia, FSA did not show a difference between any of the
      categories. With increasing age of all subjects, the changes in FSA indicated a
      significant increase in the number of fine horizontal and vertical trabeculae. No
      correlation was found between the subjects' body weight and changes in the
      subarticular cancellous bone organisation. CONCLUSIONS: FSA quantifies changes in
      cancellous bone organisation in knee osteoarthritis. In the diseased compartment,
      increased horizontal trabecular thickness occurred early and preceded the later
      changes in the vertical structures.

PMID- 8984942
TI  - Further validation of the BILAG disease activity index in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To examine the association among the BILAG disease activity index
      components and their relations with global assessments, health status, and
      laboratory tests with regard to the validity of the BILAG index. METHODS: A cross
      sectional study of consecutive patients with systemic lupus erythematosus (SLE)
      attending a specialist lupus outpatient clinic between July 1994 and February
      1995. The internal consistency of the British Isles Lupus Assessment Group
      (BILAG) index-a disease activity assessment system for SLE patients, based on the
      principle of the physician's intention to treat-was examined using Cronbach's
      coefficient alpha. The association of the components of the BILAG index with
      health status as measured with the MOS Short Form 20 (SF-20), with patients' and
      doctors' global assessments of patient wellbeing and with laboratory tests was
      analysed with Spearman rank correlations. RESULTS: 133 female and eight male
      patients, age 20.1 to 88.7 years (mean 41.1, SD 12.5), were included. With few
      exceptions, the components of the BILAG index which reflect disease activity in
      different organ systems were not associated with each other. With the exception
      of the mucocutaneous component, we found a significant relation between all
      components of BILAG and global assessment of patient wellbeing, health status,
      erythrocyte sedimentation rate, or serum C3 level. CONCLUSIONS: The study
      confirms the validity of all but the mucocutaneous component of the BILAG index.
      However, disease activity in different organ systems in SLE does not follow a
      common pattern. Thus the individual BILAG components should be used rather than
      the total BILAG score as a primary endpoint in clinical and epidemiological
      studies. To capture the total effect of SLE on an individual measures of disease
      activity, damage, and health status are all needed.

PMID- 8984943
TI  - Safety and efficacy of recombinant gamma interferon in the treatment of systemic
      sclerosis.
AB  - OBJECTIVE: To evaluate the safety and efficacy of recombinant gamma interferon
      (rIFN gamma) in the treatment of patients with systemic sclerosis. METHODS:
      Sixteen patients with systemic sclerosis were treated with r-IFN gamma, 60
      micrograms m-2 (low dose, n = 10) and 150 micrograms m-2 (high dose, n = 6),
      three times weekly in an open phase I/II trial of eight months duration. The
      patients were stratified in low and high dose according to the severity and the
      extent of scleroderma; the two groups were comparable. RESULTS: The treatment was
      well tolerated. The most common side effects, almost certainly related to r-IFN
      gamma, were fever, chills, dizziness, headache, and severe flu-like syndrome with
      decreasing intensity with the time of treatment. Severe aphthous stomatitis (n =
      1), ventricular tachycardia (n = 1), severe oesophageal ulcers due to gastro
      oesophageal reflux (n = 1), disease exacerbation alone with frank arthritis and
      slight pericardial effusion (n = 1), and inability to conform to the requirements
      of the study (n = 1) were the reasons for discontinuing treatment. Side effects
      and degree of response were evident during the first five months of treatment. A
      significant decrease in mean skin thickness score was observed and was higher in
      the high dose group. Reactive oxygen species of peripheral neutrophils and
      soluble interleukin-2 receptor serum concentrations were higher than those of
      normal individuals at study entry and decreased in parallel with clinical
      improvement. CONCLUSIONS: Treatment of systemic sclerosis patients with r-IFN
      gamma was relatively safe and well tolerated for doses as high as 150 micrograms
      m-2 three times weekly. Side effects and the degree of response can be seen
      during the first months of therapy and can be used as predictors of ultimate
      toxicity or response. The drug seems to be effective in treating cutaneous
      scleroderma.

PMID- 8984944
TI  - Minocycline induced arthritis associated with fever, livedo reticularis, and
      pANCA.
AB  - OBJECTIVE: To describe a novel iatrogenic immunological reaction produced by
      minocycline. CASE REPORTS: The clinical course and laboratory results of three
      women who presented with similar rheumatological manifestations after a prolonged
      exposure to minocycline are described. All three presented a unique reaction
      manifested by fever, arthritis/arthralgia and livedo reticularis during treatment
      with minocycline for acne vulgaris. The clinical syndrome was associated with
      high titre of serum perinuclear anticytoplasmatic antibodies (p-ANCA) and
      antimyeloperoxidase antibody (anti-MPO). Symptoms resolved after stopping the
      drug and recurred promptly after rechallenge in all three patients. CONCLUSIONS:
      Minocycline, which is widely used in the treatment of acne, often without
      adequate supervision, may induce arthritis and livedo vasculitis associated with
      anti-MPO.

PMID- 8984945
TI  - Influence of interleukin 1 beta on tenascin distribution in human normal and
      osteoarthritic cartilage: a quantitative immunohistochemical study.
AB  - OBJECTIVE: To determine the influence of IL-1 beta on the presence and the
      distribution of tenascin in matrix of human normal and osteoarthritic cartilage
      explants. METHODS: Cartilage was grown in organotypic culture with or without IL
      1 beta (10 ng ml1). Tenascin antigen was detected on cryopreserved cartilage
      sections by immunohistochemical techniques with a monoclonal antibody directed
      against all tenascin isoforms (BC-4), and then quantified by video imaging
      densitometry. RESULTS: Tenascin was present in normal cartilage explants and
      increased in osteoarthritic cartilage explants. Treatment of normal and
      osteoarthritic cartilage explants with IL-1 beta (10 ng ml-1) induced an increase
      in tenascin content, which was particularly high in normal cartilage and
      predominated in the superficial layers of damaged cartilage. There was no obvious
      correlation between proteoglycan loss and presence of tenascin. CONCLUSIONS: In
      human normal and osteoarthritic cartilage explants, the presence and the
      distribution of tenascin are influenced by IL-1 beta.

PMID- 8984946
TI  - Association of complement alleles C4AQ0 and C4B5 with rheumatoid arthritis in
      Koreans.
AB  - OBJECTIVE: To investigate the association of complement C4 allotypes with
      rheumatoid arthritis in Koreans. METHODS: 65 rheumatoid arthritis patients and
      255 controls were typed for C4 allotypes and HLA-A, B, C, DR, and DQ antigens.
      RESULTS: The frequencies of C4AQ0 (32.3% v 14.9%, P < 0.005) and C4B5 (29.2% v
      12.2%, P < 0.005) were significantly increased in rheumatoid arthritis patients
      compared with healthy control subjects. Among rheumatoid patients, the frequency
      of C4AQ0 was significantly increased in both the rheumatoid factor (RF) positive
      (27.3%) and the RF negative (66.7%) subgroups. The frequencies of C4B5 and HLA
      DR4 were significantly increased only in RF positive subgroup. C4B5 was strongly
      associated with HLA-DR4, whereas C4AQ0 did not show association with DR4.
      CONCLUSIONS: In Koreans, C4AQ0 and C4B5 are associated with susceptibility to
      rheumatoid arthritis, as in the Japanese. C4B5 is strongly associated with HLA
      DR4. C4AQ0 is considered to be a DR4 independent risk factor, and a disease
      susceptibility allele in linkage disequilibrium with C4AQ0 is suggested in Korean
      patients with rheumatoid arthritis.

PMID- 8984947
TI  - Autologous haemopoietic stem cell transplantation in a patient with severe
      pulmonary hypertension complicating connective tissue disease.

PMID- 8984949
TI  - Notice of redundant publication.

PMID- 8984950
TI  - [Arterial mechanics in cardiovascular pathology].

PMID- 8984951
TI  - [Role of nitric oxide in the modulation of the vascular response to angiotensin
      II in hypertensive rats].
AB  - Vasorelaxant activity induced by nitric oxide has been associated with a
      regulator activity on the blood pressure. In the present study we evaluated the
      nitric oxide contribution of the regulation of angiotensin II-induced
      vasoconstriction in normotensive rats and aortic coarctation-induced hypertensive
      rats. Renal vascular reactivity to angiotensin II was evaluated in the presence
      and absence of nitric oxide synthesis inhibitor; NG-nitro-L-arginine methyl
      ester. Nitrite concentration in perfusate was measured as an index of nitric
      oxide released and nitric oxide synthase activity was determined by production of
      3H-L-citrulline. Renal NG-nitro-L-arginine methyl ester perfusion potentiated
      angiotensin II-induced vasoconstriction in normotensive rats but did not affect
      angiotensin II effect on hypertensive rats. The release of nitrites was lower in
      the kidneys from hypertensive rats than normotensive rats. Renal nitric oxide
      synthase activity was decreased in the hypertensive rats compared to the
      normotensive rats. We suggest that in normotensive rats, nitric oxide counteracts
      angiotensin II vasoconstrictor action, whereas, in hypertensive rats this
      mechanism is impaired, therefore, potentiating angiotensin II increase in
      vascular resistance thereby contributing to the developing of high blood
      pressure.

PMID- 8984948
TI  - The association between fibromyalgia and carpal tunnel syndrome in the general
      population.

PMID- 8984952
TI  - [Intravascular ultrasound. Initial experience and review of the literature].
AB  - From February 1995 to February 1996, 52 patients underwent intravascular
      ultrasound (IVUS) imaging: three with aortic coarctation (AoCo), one with
      persistent ductus arteriosus (PDA), 5 with rheumatic heart disease (RHD) and
      normal coronary arteries by angiography, one with muscular bridge in anterior
      descending artery, 20 with percutaneous transluminal coronary angioplasty PTCA
      (Group I), one of them with eximer laser and 22 stents (Group II). In patients
      with AoCo was possible to observe obstruction mechanism and the effect of
      dilation. In patient with PDA we measured the diameter of ductus. In patients
      with RHD we found early atherosclerosis in four cases, no detected by
      angiography. In Group I, we found soft plaque in 8, fibrous/mixed in 7 and
      calcified plaque with the calcium located superficially near the lumen in 5,
      concentric in 6 and 14 eccentric plaques. In this group the objective was
      observational in most of the cases, except when the imaging was characteristic of
      mayor dissection or small final lumen. In 10 cases we observed fracture or
      dissection of the plaque, in some with small flaps into the lumen. In the last
      two cases, IVUS was used to optimize results after PTCA in one, in the other we
      postponed the procedure because the characteristics of the lesion (severe
      superficial calcification). The patient who underwent eximer laser, IVUS
      demonstrated irregular and small lumen and was followed by PTCA. In Group II,
      IVUS was used to optimize deployment of stents. We did not have any case with
      subacute thrombosis. COMPLICATIONS: Only four cases had angina with ischemic ECG
      changes during the procedure, but reverted after catheter pullback and
      intracoronary nitroglycerin. In summary, IVUS gives information about mechanism
      of obstruction, its complications and results of PTCA. Also detect early
      atherosclerotic disease not observed by angiography. Optimize deployment of
      stents and avoids cumarinic anticoagulation in most of the patients. Rational
      selection of device or deferral of the procedure is possible if we know the
      characteristics of the plaque before intervention. Utility in other
      cardiovascular diseases is limited at this time. It's a safe procedure, the
      morbidity is low and in our experience, without mortality. In the future this new
      technology will bring useful information in other types of coronary arteries
      diseases.

PMID- 8984954
TI  - [Use of intracoronary stents without anticoagulants. Experience of the Hospital
      Espanol of Mexico].
AB  - Our initial experience with intracoronary stenting without oral anticoagulant is
      presented. From december 1994 to december 1995 we implanted 58 stents in 43
      patients (36 males). Indications were: retraction 1, restenosis 3, dissection 8,
      acute myocardial infarction 13 and de novo 33. All patients received ticlopidin,
      aspirin and diltiazem before the procedure, heparin and intracoronary
      nitroglycerin were given during the procedure, and ticlopidin and aspirin for the
      next six weeks. Non-compliant balloons at 14-16 atmospheres were used for stent
      implantation. The balloon/artery ratio was 1:1. Implant sites were: 29 in left
      anterior descendent, 17 in right coronary artery, 7 in circumflex and 5 in vein
      grafts. This procedure was successful in 40/43 (93%) patients. One patient died
      and 2 had acute occlusion. One patient underwent coronary artery bypass grafting
      and the other underwent a new dilatation with higher pressure. There were no
      subacute occlusions. During 140 days mean time follow up: 2 patients had angina
      (incomplete revascularization) and 27 patients with negative stress test. No
      myocardial infractions or deaths were present during the follow up period. Stent
      implantation with high pressure technique and without oral anticoagulant in
      coronary arteries greater than 3.0 mm is a safe and effective method with high
      rate success and very low acute complication rate.

PMID- 8984953
TI  - [Hemodynamic effects of oral captopril in patients with critical aortic
      stenosis].
AB  - OBJECTIVES: To analyse the hemodynamic and ventricular function effects of oral
      captopril in severe aortic stenosis. PATIENT POPULATION: inclusion criteria:
      patients older than 18 years with critical aortic stenosis. EXCLUSION CRITERIA:
      angiotensin-converting enzyme inhibitor used previously contraindication to right
      catheterisation aortic insufficiency, valvular prosthesis in aortic position, or
      other valvulopathy. As well as the need for immediate valvular aortic replacement
      arrhythmia, A-V conduction alterations, or ventilatory support. PROTOCOL:
      prospective, no randomized. Swan-Ganz catheter was used. Basal hemodynamic
      measurements were made on 1, 2, 4, 6 and 8 hours during 48 hours. Captopril was
      administered 12.5 mg first and then 8 mg tid (6 doses). STATISTICAL ANALYSIS:
      Neuman-Keuls test was used for multivariate comparisons. Statistical significance
      was determined with P < 0.05. RESULTS: 22 patients were analyzed. Systemic
      vascular resistance fell from 1750 Dyn/seg/cm-5 to 1200 (P-0.001), cardiac output
      increased from 4.1l/min to 5.8 (P-0.001), cardiac index increased from 2.4
      l/min/m2 to 2.9 (P-0.009), stroke volume from 47 ml to 64 (P-0.04) and stroke
      volume index from 27 ml/m2 to 36 (P-0.002). In patients with heart failure (n =
      7) the systemic vascular resistance fell from 2050 Dyn/seg/cm-5 to 1463 (P-0.04),
      cardiac output increased from 2.8l/min to 4.1 (P-0.04), cardiac index from 2.07
      l/min/m2 to 2.75 (P-0.04), stroke volume from 46 ml to 64 (P-0.03), pulmonary
      capillary wedge pressure fell from 19 mmHg to 16 (0.04) and the systolic
      pulmonary arterial pressure fell from 63 mmHg to 42 (P-0.009). CONCLUSIONS:
      captopril improves the hemodynamic parameters in patients with critical aortic
      stenosis, principally in those with heart failure.

PMID- 8984955
TI  - [Cor triatriatum. Diagnostic and surgical experience].
AB  - Five cases with cor triatriatum were diagnosed in less than a two years period.
      There were 4 females and one male. The mean age was 3.6 years. Three patients
      were operated on successfully. One patient died shortly after cardiac
      catheterization in acute pulmonary edema, another case is waiting for surgery
      with mild obstruction. We do not have a complete explanation for this high
      incidence of cor triatriatum. The utility of Echo Doppler color in diagnosis is
      highlighted. A literature review is made.

PMID- 8984956
TI  - [Total electrical alternans and changes in auricular repolarization in a newborn
      infant].
AB  - A premature 3 days-old female with AV block Mobitz type II and structurally
      normal heart is presented. Progressive atrial abnormal repolarization was
      observed. Besides, transient total electrical alternans that included P wave, QRS
      complex, ST segment and T wave was evident. Retrospective analysis on ECG
      findings showed multiple metabolic and electrolytic disturbances related with
      this phenomenon. Hypoxia, hypothermia and long QT interval around an immature
      heart are particularly discussed as triggering factors.

PMID- 8984957
TI  - [Percutaneous mitral commissurotomy using Inoue's balloon during pregnancy].
AB  - The authors present three cases of pregnant women with symptomatic severe mitral
      stenosis with a mean age of 28.6 +/- 2.3 years, and during 27.6 +/- 1.52 weeks of
      pregnancy. Two patients were in class III and one in class IV of the New York
      Heart Association (NYHA). All patients had a mitral valvular area equal or less
      than 1 cm2, with a Wilkins score of 7 to 9 and mitral insufficiency grade I in
      two cases; two, had severe pulmonary arterial hypertension (mean > 50 mm Hg).
      After Percutaneous Mitral Valvuloplasty (PMV) the mitral valve measured by 2D
      echocardiography increased form 0.83 +/- 0.2 cm2 to 1.8 +/- 0.15 cm2; the mean
      transmitral gradient diminished from 13 +/- 3.4 mm Hg to 3.6 +/- 1.15 mm Hg; the
      degree of mitral insufficiency was no modified in neither case. Hemodynamic
      results revealed increasing of the mitral valve from 0.83 +/- 0.18 cm2 to 2.23 +/
      0.3 cm2; the mean mitral gradient decreased from 21.6 +/- 9 to 4.3 +/- 0.5 mm
      Hg; the mean left atrial pressure from 30 +/- 12 to 12.3 +/- 4 mm Hg; the mean
      pressure of the pulmonary artery diminished suddenly from 44.3 +/- 16 to 25.6 +/-
      11 mm Hg. The average fluoroscopic time was 15.3 +/- 3 minutes. There were no
      complications. The patients were discharged 48 hours after the procedure and
      continued their pregnancies in class I NYHA, which resolved in a non complicated
      vaginal delivery with normal products. We conclude that PMV is a safe and useful
      therapy in pregnant patient with severe mitral stenosis refractory to medical
      treatment.

PMID- 8984958
TI  - [Death with dignity and medical decision. 1979].

PMID- 8984959
TI  - [Basic concepts on the genesis and significance of myocardial hypertrophy].

PMID- 8984960
TI  - [The development of cardiology in the evolution of scientific thinking].

PMID- 8984961
TI  - [Changes in lipid availability in Venezuela, 1970-1992].
AB  - The authors carry out a research focused on the quantification and analysis of
      the main changes in feeding and nutrition in Venezuela between 1970 and 1992.
      Such research started with the review and adjustment of the Food Balance Sheets
      (Hojas de Balance de Alimentos) elaborated by the Instituto Nacional de Nutricion
      (National Nutrition Institute) between 1970 and 1979 in order to homogenize them
      in a methodological way to make them similar to those elaborated by that
      institution and the Fundacion Polar for the 1980-90 period. Estimates were made
      about the daily and per person availability of food for human consumption (DCH)
      for 1991 and 1992. This report, a partial product of that research, characterizes
      the evolution of the lipidic DCH in Venezuela for the 1970-1992 period. This
      period has been divided in seven stages of the evolution of the total energetic
      DCH, as this reflects well the course of the daily and per person Food Purchasing
      Power (PCA); there is a direct and strong functional relationship between these
      two variables. Along those stages the behaviour of the lipidic DCH is studied and
      we try to view possible relationships between the evolution of the Venezeluans
      economical situation and the absolute and relative variations observed in the
      level and the structure of the lipidic DCH. This structure is analyzed from
      several points of view: groups of food sources, origin, "visibility", and place
      of origin. One purpose is to determine also which food groups are mainly
      responsible for the venezuelan's external lipidic dependence. A general picture
      of the evolution of the DCH for saturated fatty acids and cholesterol is made, as
      well as of the variations experienced by the P/S and M/S relationships. It was
      found that the most dynamic elements, those that can explain a very high
      percentage of the variations observed in the level and the structure of the
      lipidic DCH were: the groups of foods of Visible Fats, Milk and dairy products,
      and Meats; vegetal lipids; vegetal-visible and animal-invisible lipidic
      fractions; imported lipids or lipids of food products which raw materials were
      imported (oily raw materials to make oils and edible solid fats, and raw
      materials to make food for poultry and hogs). The importance of the food groups
      Visible Fats, Milk and dairy products, and Meats, as sources or saturated fatty
      acids in the diet of the Venezuelans was made evident (89-91% of the respective
      total DCH), as well as the importance of the food groups Eggs, Meats, Fish and
      Seafood, and Milk and dairy products, as sources of cholesterol (82-89% of the
      available total). It was found that the lipid-originated calories account for
      less than 30% of the total energetic DCH; saturated fatty acids account for less
      than 10% of the available calories/person/day; the DCH for cholesterol did not
      reach the level of 300 mg/p/d; the P/S and M/S relationships remained close to 1.
      These last four facts are considered favorable for the health of the human being.

PMID- 8984962
TI  - [Technological innovation applicable to marine oils rich in n-3 fatty acids to
      allow their nutritional and pharmacological use: a challenge for the present
      decade].
AB  - The important physiological properties described for marine oils rich in n-3
      polyunsaturated fatty acids have give rise to increasing efforts to develop
      procedures for obtaining, preserve and concentrate these oils aiming its
      nutritional and pharmacological use. The fish meal industry provides high
      quantities of fish oil, however this oil being not suitable for human consumption
      must be subjected to different refining procedures to allow its use for feeding
      purposes. This review describes the current research about the employment of
      different procedures to incorporate n-3 polyunsaturated fatty acid to our
      feeding. The feasibility for the application of chemical methods and
      stereospecific enzyme-transesterification procedures for obtaining oil
      concentrates, and the use of natural substances for stabilizing the oil against
      oxidation are discussed. The possibility that some birds such as the chicken,
      feeding a diet rich in n-3 polyunsaturated fatty acids, as a healthy, safe and
      suitable vehicle to provide these fatty acid for human nutrition is also
      discussed.

PMID- 8984963
TI  - [Ecological and food safety considerations about products of vegetable origin].
AB  - Media have paid much attention in recent years to emerging microbiological
      problems in foods of plant origin. The potential for contamination of fruits and
      vegetables is high because of the wide variety of conditions to which produce is
      exposed during growth, harvest, processing and distribution. These considerations
      acquire great significance in the current scenario of the new processing
      techniques that offer attributes of convenience and fresh-likeness in response to
      changes in consumption patterns and increased demand of fresh and minimally
      processed fruits and vegetables. Thus, reliance on low temperature storage and on
      improved packaging materials/techniques have increased. Even if produce had not
      been considered a major vector for foodborne diseases, technologies that extend
      shelf-life by decreasing the rate of product deterioration might increase the
      risks associated with pathogenic microorganisms, especially of psychotropic
      nature, by allowing sufficient time for their growth when retarding the
      development of competitive spoilage organisms. Processing steps that modify the
      food microenvironment open new possibilities to support pathogens that, for
      ecological reason, would have never been naturally present in produce. Ecological
      and safety aspects related to fruits and vegetables as well as foodborne disease
      outbreaks traceable to produce and reportedly due to Salmonella and Shigella
      spp., Listeria monocytogenes, Clostridium botulinum, Aeromonas hydrophila,
      Campylobacter jejuni are reviewed.

PMID- 8984964
TI  - [Evaluation of the Reinforced subprogram of the Chilean National supplemental
      Nutrition Program].
AB  - Chile's National Supplementary Feeding Program constitutes the main food
      intervention program of the country. Its annual budget amounts to US $ 65 million
      covering approximately 55% of the national population of children under 6 years
      of age. It includes two subprograms, the Basic one for normally growing children
      and the Reinforced one for undernourished children and those at risk of becoming
      undernourished. This last group amounted in 1990 to 17% of the total, receiving
      50% of the food distributed. This study is the first evaluation carried out on
      the Reinforced subprogram, having as general objective to measure its efficiency
      in terms of the change in the nutritional status of the targeted children.
      Presently, children under two are targeted if a) are undernourished by wt/ht (< 
      1 S.D. NCHS) or b) have less weight increase than 75% of the Ministry of Health's
      norm (similar to NCHS) during two consecutive health controls. The only way these
      children are discharged is, if during three consecutive controls (monthly) they
      increase more than 75% of the same norm. The analysis involved nutritional
      evaluations at birth, when the children were targeted and when they were
      discharged, showing that the improvement of their nutritional status was very
      unsatisfactory.

PMID- 8984965
TI  - [Bioassay of rainbow trout (Oncorhynchus mykiss) pigmentation using ancho chili
      (Capsicum annuum) extracts].
AB  - Farming of trout requires a finishing diet containing pigments such as
      astaxanthin and canthaxanthin so that they may achieve a pink tissue coloration
      similar to that of wild trout. The production of synthetic pigments is not enough
      so that the requirements of the aquaculture industry are not met, besides having
      a high cost. Thus, the objective of the present study was to evaluate the
      deposition of saponified and esterified chili (Capsicum annuum) extracts in the
      skin and muscle of rainbow trout (Oncorhynchus mykiis). The experiment consisted
      of three treatments with the inclusion in the finishing diet of saponified and
      esterified chili extracts and of astaxanthin, respectively. Each treatment was
      carried out with 150 organisms with an average weight of a 150 g and done in
      duplicate. The results showed that both the saponified and esterified chili
      extracts pigmented the skin and muscle of rainbow trout, although the
      pigmentation effect was less red than that produced by the astaxanthin control.

PMID- 8984966
TI  - [Development and optimization of an isotonic sports drink].
AB  - Within a research program on food products for athletes starting from natural
      apple concentrate, the design, manufacture and control of isotonic beverages, was
      undertaken. The dilution conditions for the apple concentrate were established
      studying several salts combinations which will supply those electrolytes that are
      eliminated through sweat and have to be replenished. They are sodium, potassium,
      chloride, magnesium and calcium in concentrations such as to supply an osmotic
      pressure similar to that observed in blood. The addition of a premix of vitamins
      (B1, B2, B6, B12, C, E, folic acid, niacin, pantothenic acid and biotin) in
      several levels of the Recommended Daily Allowance (RDA) (100, 75, 62.5, 60 and
      30% of the RDA) was assayed. The obtained formula tasted salty and medicine-like,
      therefore the vitamin content had to be reduced, supplying 30% of the RDA in a
      premix constituted by those vitamins which are the most important for physical
      activity (B1, B2, B6 and C). The quality of the formula was optimized considering
      variables such as flavor, color and maltodextrin levels by using methods of
      sensory evaluation. In the elaborated beverage controls such as pH, acidity,
      total solids (degree Bx), relative density and soluble solids/acidity ratio
      complying with the corresponding standards, were carried out. In addition,
      chemical composition, caloric value, microbiological and sensory quality, were
      controlled. The fruit juice was packed in a 250 ml self-supporting"Doy-Pack"-like
      bag. Both, microbiological and sensory quality were good, and the caloric value
      was 101.18 Kcal/250ml. Shelf life studies at two different temperature conditions
      15-25 degrees C and 3-5 degrees C, were carried out. The limiting factor was
      flavor which defined a shelf life of at least 3 months, stored at refrigeration
      temperature (3-5 degrees C). The formulated beverage supply the electrolyte
      concentrations which allows to be characterized as isotonic beverage, recommended
      for athletes.

PMID- 8984967
TI  - [Production of biological silage from fish scraps].
AB  - Fish waste from the fish processing industry were used as a raw material to
      produce biological silage. The technology used had been previously developed and
      tested to optimize the process. The degree of grinding, molasses concentration,
      process temperature, Lactobacillus plantarum inoculation, and utilization of
      tropical fruit wastes as a source of proteolytic enzymes were tested. Results
      indicated that after process and storage for 90 days at room temperature, a
      stable product is obtained by using no less than 15% of molasses and 10% of fruit
      waste, process temperature should be around 40 degrees C, the fish have to be
      ground to a very small particle size, and microbial inoculation is necessary.

PMID- 8984968
TI  - [Chemical changes in colostrum fermented with sorghum].
AB  - Colostrum from Holstein cows was collected during the first three days post
      partum. Ground sorghum (7.5%) was added to it. Untreated colostrum used as
      control, and sorghum treated colostrum samples were allowed to ferment for 0, 8
      or 21 days at 18-20 degrees C in glass containers; pH, moisture, crude protein,
      digestible protein, ammonia, lactic acid and total energy were analyzed in
      untreated and treated samples. Crude protein was not significantly different (P >
      0.01) in control colostrum (7.12, 5.76, 5.70%) and treated colostrum (6.66, 5.71,
      5.98%) at 0, 8 and 21 days of fermentation respectively. Digestible protein was
      higher (P < 0.01) in the untreated (90.0, 93.0%) than in the treated colostrum
      (89.0, 81.0, 86.0%). Ammonia content was also higher (P < 0.01) in the control
      (0.25, 1.31, 1.37%) than in the treated one (0.23, 0.97, 1.20%). Lactic acid was
      lower (P < 0.01) in the untreated colostrum (0.82 g/100 ml) than in the treated
      colostrum (1.24 g/100 ml) after 21 days of fermentation. Total energy values were
      lower (P < 0.01) at 8 and 21 days of fermentation in the untreated (0.91, 0.84
      Kcal/g) than in the treated colostrum (1.16, 0.97 Kcal/g). The addition of
      sorghum to colostrum reduced the crude, protein degradation and the ammonia
      content after 8 and 21 days of fermentation, increasing total energy and lactic
      acid content after 21 days of fermentation.

PMID- 8984969
TI  - [Electrophoretic analysis of buckwheat flour compared with regular wheat flour].
AB  - The composition of the alcohol soluble proteins (prolamins) obtained from
      buckwheat meal and common wheat flour by two procedures were analysed by
      electrophoresis at pH 3.1 and, after dissociation, in the presence of sodium
      dodecyl sulphate at pH 8. The profiles obtained from the prolamin fraction of
      buckwheat were very different, qualitatively and quantitatively, from those of
      the prolamin of common wheat. It is probable therefore that the adverse effects
      associated with the presence of wheat gliadin in diets of patients with celiac
      disease would be reduced and possibly avoided if wheat flour were replaced by
      flour from buckwheat.

PMID- 8984970
TI  - [Factors which modify the nutritional state of iron: tannin content of herbal
      teas].
AB  - Tannins are natural compounds that abound in herbs, wood and fruits. Their
      numerous hydroxyl radicals confer them a strong avidity for metals such as Fe, Zn
      and Cu. This property makes them strong inhibitors for the gastrointestinal
      absorption of these metals. Our purpose was to determine the tannin content of
      herbal infusions commonly consumed in Chile and other Latino American countries.
      The determination was performed from dessicated herbs with the Folin-Denis
      technique. Yerba mate, tea and oregano had the highest tannin content (117, 100
      and 84 mg of tannic acid/g dry herb respectively). An intermediate level (between
      20 and 40 of tannic acid/g) was for coca, matico, boldo, palto, laurel, orange
      and binojo. The lowest level of tannin for paico, cedron, apio and manzanilla (<
      10 mg/g). We conclude that the consumption of herbal teas at or around meals may
      inhibit the absorption of metals such as Fe, Zn, or Cu by decreasing their
      bioavailability.

PMID- 8984971
TI  - [Hydrogenated products in Brazil: trans isomers, physico-chemical characteristics
      and fatty acid composition].
AB  - The shortening Brazilian market has wide range of products for specific use,
      mainly at industrial level. In the present work 19 samples of shortenings, 14
      samples of margarines and 9 samples of spreads were studied. Iodine index,
      softening point, trans fatty acids, solid fat content and fatty acid composition
      were determined in all samples. High levels of trans fatty acids in most of the
      samples were observed (30%), varying between 0-62%. Correlations for thermal
      characteristics of the samples between the fat groups were not found. In Brazil
      most of shortenings are produced for blends of soy bean oils with different level
      of hydrogenation.

PMID- 8984972
TI  - Subarachnoid hemorrhage after aneurysm surgery.
AB  - The surgical treatment of intracranial aneurysms by clipping is recognized as
      effective and definitive. However some cases that suffered a new subarachnoid
      hemorrhage (SAH) some time after they were submitted to aneurysm clipping have
      raised doubts about the concept of "cure" after this treatment. Eleven patients
      previously submitted to aneurysm clipping who presented a new SAH were analyzed.
      The time elapsed from surgery to SAH varied from 3 to 10 years. After SAH four
      patients had a poor outcome. The new episode of SAH occurred due to intrinsic
      factors of the cerebral vasculature: 1. a weak point of the vessel wall near the
      previous aneurysm, 2. a weak point of another vessel far from the previous
      aneurysm, 3. a previous infundibular dilation of the posterior communicating
      artery; and due to technical problems: 1. aneurysm not identified during the
      previous treatment, 2. aneurysm deliberately left untreated, 3. persistence of
      the aneurysm due to inappropriate surgery, 4. persistency of part of the aneurysm
      neck after clipping and 5. slipping of the clip from the neck of the aneurysm.
      The measures to prevent new SAH after surgery start with adequate preoperative
      angiographic studies, a careful inspection of the position of the clip and
      emptying of the aneurysm. Early angiography studies may reveal a persistent neck
      and later ones may reveal newly developed aneurysms. In conclusion, SAH after
      aneurysm clipping is a late and severe phenomenon and the concept of "cure" after
      this surgery should be interpreted with caution.

PMID- 8984973
TI  - Clinical manifestations of peripheral nervous system involvement in human chronic
      Chagas disease.
AB  - We conducted a clinical and electromyographical study in patients with Chagas'
      disease in the indeterminate or chronic stages of the illness. Altogether 841
      patients were examined. Only 511 were admitted within the protocol; the remainder
      patients were rejected because they showed other causes able to damage the
      nervous system. Fifty two (10.17%) out of the 511 patients showed signs and
      symptoms of peripheral nervous system involvement in the form of sensory
      impairment and diminished tendon jerks suggesting the presence of neuropathy.
      Forty five of them were submitted to a conventional electromyographical
      examination. Fifteen of them showed normal results, while the remainder 30
      disclosed a reduced interference pattern, being most of the remaining motor unit
      potentials fragmented or poliphasic, reduced sensory and motor conduction
      velocities and diminished amplitude of the sensory action potential. The findings
      suggest that some chagasic patients in the indeterminate or chronic stages of the
      disease may develop a clinical mild sensory-motor peripheral neuropathy.

PMID- 8984974
TI  - [Intermittent prophylaxis in febrile seizures with oral diazepam: study of 82
      cases].
AB  - We present our results of intermittent prophylaxis with oral diazepam in febrile
      seizures. We treated 82 patients aged between 3 months and 5 years. They have had
      simple or complex febrile seizures. Recurrence occurred in 22 patients (26%),
      none had a long-lasting febrile convulsion. Transient side effects occurred in
      21.95% of the cases. We conclude that diazepam is a safe and effective drug for
      prophylaxis of febrile seizures when used as soon as any sign of illness appears.
      We suggest, however, that the administration of the drug should be indicated if
      the child presents at least one consistent predictor of risk of recurrent febrile
      seizures.

PMID- 8984975
TI  - [Electroencephalographic changes in patients with congenital adrenal hyperplasia
      due to 21-hydroxylase deficiency].
AB  - Electroencephalographic changes have been detected in children with premature
      pubarche. These findings might be the result from past or current central nervous
      system dysfunction, or from increased sex steroids. In order to test the last
      assertion we have performed electroencephalographic studies in 10 patients (7F,
      3M) with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency,
      of whom 4 classic and 6 nonclassic forms of the syndrome. Traditional neurologic
      examination was performed in 7 patients, the result being considered normal in
      everyone, while evolutional neurologic examination detected hyperactive
      disturbance and attention deficit in two patients. In another patient, the
      clinical findings were compatible with delay of neuropsychomotor development.
      Quantitative electroencephalography with brain mapping in patients over three
      years-old (n = 9), and conventional EEG in the remaining patient, were considered
      abnormal for age in 8 patients (80%), the record being characterized as slow in 7
      patients. The high rate of electroencephalographic changes in this sample, as
      well as in premature pubarche, suggests that these findings might result from
      high inappropriate for age androgenic levels, and warns about the importance of
      neurologic examination and follow-up in children with CAH.

PMID- 8984976
TI  - [Preditive clinical factors for epileptic seizures after ischemic stroke].
AB  - Preditive clinical factors for epileptic seizures after ischemic stroke. Clinical
      features of 35 patients with ischemic stroke who developed epilepsy (Group 1)
      were compared with those of 35 patients with ischemic stroke without epilepsy
      (Group 2). The age of the patients did not differ between the groups. There were
      more men than women and more white than other races in both groups. Diabetes
      melitus, hypertension, transient ischemic attack, previous stroke, migraine,
      Chagas disease, cerebral embolism of cardiac origin and use of oral contraceptive
      did not differ between the groups. Smokers and alcohol users were more frequent
      in Group 1 (p < 0.05). Most patients of Group 1 presented with hemiparesis; none
      presented cerebellar or brainstem involvement. Perhaps strokes in smokers have
      some different aspects, that let them more epileptogenic than in non smokers.

PMID- 8984978
TI  - [Multimodal iatrogenic apathy].
AB  - The present paper reports on five patients who developed apathy as a peculiar
      side effect of antidepressants. Their behavioral and psychopathological changes
      were primarily due to the near-absence of emotional experience, a key
      characteristic that distinguishes apathy from avolition and abulia. The emergence
      of apathy in the course of an antidepressant treatment should raise the suspicion
      of an adverse effect of the drug and lead to its prompt withdrawal. A sample of
      the relevant clinical evidence favoring the distinction of apathy confined to a
      single sensory domain ("unimodal apathy") from apathy confined to more than one
      sensory realm ("multimodal apathy") is reviewed. From a pathophysiological
      standpoint, it would appear that neural nets centered in the amygdala-temporo
      polar cortex are critical for the integration of sensory perceptions and mental
      imagery with appropriate emotional tone and quality as well as with their
      accompanying somatic markers, as they receive afferents from the major projection
      systems of the prosencephalon and lie in nodes strategic to modify the ongoing
      activity of multiple parallel brain systems. The fact that one common symptom can
      be produced by such a heterogeneous family of substances points to a shared
      neurochemical mechanism of action. At present, discrete cerebral serotoninergic
      circuits would appear to be suitable candidates for such a role. Cases as these
      may be critical for the understanding of the cerebral organization of emotions in
      man, lending support to the notion that distinct neurochemical systems mediate
      discrete psychopathological symptoms.

PMID- 8984977
TI  - [Pregnancy, puerperium and cerebrovascular disease].
AB  - Six patients who presented cerebrovascular disease during puerperium or pregnancy
      were studied. One of them presented hemorrhagic stroke caused by intracerebral
      bleeding due to pre-eclampsia. Three patients presented ischemic stroke, they all
      had positive serologic reactions for Chagas' disease, but only two of them had
      clinical cardiopathy; one of these patients had anticardiolipin antibody. The
      other two patients presented cerebral venous thrombosis of sagittal sinus. Both
      were smokers and one of them used oral contraceptive. We emphasize the importance
      of clinical investigation to seek for the common causes of cerebrovascular
      disease in young people, with special attention to Chagas disease in Brazil.

PMID- 8984979
TI  - [Clinical and laboratory characteristics of 62 tuberculous meningoencephalitis
      cases].
AB  - The authors present clinical, demographic and laboratory characteristics of 62
      patients with proven tuberculous meningoencephalitis admitted at Couto Maia
      Hospital, reference for patients with infectious diseases in the State of Bahia.
      The patients' age varied from 2 months to 50 years, 59.7% of the cases with ages
      ranging from 0 to 4 years, no sex predominance. The time length for the disease
      varied from 0 to 90 days, average around 13 days. The most common signs and
      symptoms were fever and neck stiffness in 86.7 and 81.8% of the cases
      respectively. The cerebrospinal fluid showed cells varying from 4 to 1549/mm3,
      average of 406; glucose from 20 to 70 mg/dL, average of 37.3, protein from 30 to
      500 mg/dL, average of 203; lymphocyte predominance occurred in most cases,
      however in 21.3% there was predominance of neutrophils.

PMID- 8984980
TI  - [Cerebrospinal fluid in 50 AIDS patients].
AB  - Fifty AIDS patients were studied. All patients had anti-HIV antibodies (ELISA)
      present and met OPAS/Caracas punctuation criteria for AIDS cases in adults.
      Cerebrospinal fluid (CSF) analysis included pressure, cytology (number of
      cytomorphological aspects), total protein and electrophoresis, glucose and
      chloride concentration. Bacteriological and mycological investigations were
      performed as well as agglutination tests for Cryptococcus. Complement fixation,
      indirect immunoflorescence, passive hemagglutination and/or ELISA tests were
      performed for syphilis, toxoplasmosis, viral and fungal infections. All CSF
      analysis were made in the same laboratory following the same methodology. CSF was
      altered in 45 cases (90.0%) of the 50 patients studied. The most important
      alterations observed were: gammaglobulin (55.5%) and total protein (51.1%)
      increase, hypercytosis (48.9%) and decrease of chloride concentration (40.0%).
      HIV antibodies were detected in 42 patients (93.3%). Toxomoplamosis, isolated or
      associated to other agents, was the most frequent opportunistic infection
      (57.7%). Cerebrospinal fluid should always be examined in AIDS patients with or
      without neurological symptoms.

PMID- 8984981
TI  - [Mansonic neuroschistosomiasis: clinical, laboratory and therapeutic aspects].
AB  - The authors report 16 patients bearing the meningomyeloradicular form of Mansonic
      neuroschistosomiasis diagnosed according to clinical, laboratorial and image
      criteria. Patients have been observed at the Neurology Ambulatory of the Federal
      University of Bahia, within the period of April/91 to December/93. They have been
      treated with praziquantel, associated to corticosteroids. The aim has been to
      evaluate the drug's efficiency and safety in decreasing the neurological signs
      and symptoms.

PMID- 8984982
TI  - [Acute traumatic subdural haematomas: study of 110 cases].
AB  - We report a series of 110 patients with acute traumatic subdural hematoma (ASDH)
      admitted at HBDF emergency within 1994 (January 1st to December 1st). All
      patients were treated according to the same protocol. There was a predominance of
      males (79%), with ages ranging from 14 to 70, being car accidents (20%) and car
      pedestrian accidents (34%) the most frequent causes. The majority of patients
      (85.7%) was admitted in very serious condition, with a score of 8 points on the
      Glasgow Coma Scale (GCS) or lesser, which directly influenced the mortality
      rates. CT scan was the diagnostic procedure of choice, and it showed contusion
      and brain swelling to be the most frequent associated intracranial lesions.
      Surgery was carried out in 45.1% of cases and, in most instances, through an
      ample fronto-temporo-parietal craniotomy, with hematoma drainage and dural
      reconstitution. In 54.9% of cases, clinical conditions did not allow surgery and
      in this group, 69.6%.

PMID- 8984983
TI  - [Cytoplasmic inclusion bodies: a study in several diseases and a review of the
      literature].
AB  - Among 1400 muscle biopsies, we studied 16 cases with rimmed vacuoles, whose
      histology suggests cytoplasm inclusion bodies. We tried to correlate the
      clinical, laboratory and histopatological data in order to verify the specificity
      of cytoplasm inclusion bodies to certain diseases. The creatinekinase was
      increased in 10 cases. In all cases electromyography was abnormal. Muscle
      histochemistry revealed myopathy in 5 cases, mixed pattern in 7, denervation in 2
      and in 2 cases, inflammatory myopathy. Electron microscopy showed the presence of
      filaments in 8 cases (nuclear, disseminated in cytoplasm or in the subsarcolemmal
      region). The patients were classified according to history, heredity, laboratory,
      electrophysiologic, histochemistry data and electron microscopy: in myositis with
      inclusion cytoplasmic bodies (4 cases), juvenile spinal muscular atrophy (6
      cases), distal myopathies (3 cases), limb-girdle dystrophy (2 cases) and
      peripheral neuropathy (1 case). We present a revision on the pathogenesis and
      possible etiology of rimmed vacuoles and their relationship with several
      diseases.

PMID- 8984984
TI  - [Study of ultrastructural alterations in gastrocnemius muscle of C57 BL10 mice
      after prolonged ethanol ingestion].
AB  - The effects of chronic alcoholism on gastrocnemius muscle of well-nourished mice
      were morphologically studied to test the direct toxic role of ethanol on skeletal
      muscle. Thirty male young adult C57BL10 mice were divided in two groups: Group A
      (control) consisting of ten mice that drank water and Group B (alcoholic)
      consisting of twenty mice that drank 25% ethanol. All mice were allowed a
      balanced laboratory chow. The animals were kept on this ad libitum regimen under
      the same conditions of environment for 48 weeks and were weighed once a week. The
      daily dietary consumption and caloric intake were estimated, the animals having
      had a substantial weight gain, showing no signs of malnutrition. At the end of
      the experiment the animals were killed for morphological studies. No
      abnormalities were observed by conventional microscopy. Striking deviations from
      normal were verified by electron microscopy in all specimens. Dilatation of
      sarcoplasmic reticulum was a common feature, sometimes resulting in the formation
      of large vesicles and involving the terminal cisternae with the displacement of
      the triads. Areas of narrowing, splitting and loss of myofibrils were seen. Zones
      of complete disorganization of miofibrils could be occasionally observed.
      Mitochondria were generally normal. Peculiar tubular aggregates seen commonly in
      periodic paralysis and other human pathological conditions, were encountered in
      both control and alcoholic mice. Intramuscular nerves and neuromuscular junctions
      were normal. Important abnormalities in muscle capillaries were observed,
      consisting of swelling of endothelial cells and thickening of the basal lamina. A
      diffuse microvesicular lipid infiltration was seen in the cytoplasm of the
      hepatocytes which seems to be a further evidence of the toxic role played by
      ethanol. We concluded that prolonged ingestion of ethanol, representing 14.4% of
      total calories, produces in the gastrocnemius muscle of well-nourished C57BL10
      mice a distinct spectrum of ultrastructural changes which reflects a direct toxic
      effect on the skeletal muscle. These alterations are similar to those described
      in human chronic alcoholic myopathy.

PMID- 8984985
TI  - Effects of maternal proteic undernutrition on the neurons of the myenteric plexus
      of the duodenum of rats.
AB  - The purpose of this study was to verify the effects of proteic undernutrition on
      the neurons of the myenteric plexus from the duodenum of Wistar rats. Twenty-four
      animals at the age of 60 days were divided in four groups, which were named
      according to the period their mothers received hypoproteic ration (8%). Some
      segments of duodenum were subjected to histological treatment and stained with
      hematoxilin-eosin and some were used for whole mount preparations stained with
      Giemsa. We observed small, medium-sized and large neurons grouped in ganglia of
      various shapes. It was concluded that the maternal proteic undernutrition does
      not affect the organization of the myenteric plexus and that animals submitted to
      undernutrition during gestation and lactation, when normally fed, show neurons
      with strongly basophilic cytoplasm and larger cellular bodies than those from
      control animals.

PMID- 8984986
TI  - [Optic nerve gliomas: a study of 11 cases].
AB  - Optic nerve gliomas may occur alone or as components of neurofibromatosis. They
      are rare tumors accounting for 2 to 5% of all intracranial tumors and 6% of the
      intra-orbitary neoplasms. The authors present 11 cases of optic nerve-glioma
      diagnosed in Curitiba in the last 25 years. Out of these 11 patients there were
      10 women and only 1 man. The ages ranged from 3 to 25 years old, and 6 patients
      were under 15 years. In this series, 27.3% (n = 3) of the cases were associated
      with neurofibromatosis. Five patients had their tumors restricted to the optic
      nerve while the others had either extension to the optic chiasm, supra-selar
      region, frontal or temporal lobe. All the patients had pilocytic astrocytomas.

PMID- 8984987
TI  - [Cluster-tic syndrome: two case reports].
AB  - Two patients with cluster-tic syndrome are reported. The first, a 43-years-old
      man, complaining of trigeminal pain in the right side of the face, accompanied by
      homolateral autonomic signs, such as ocular injection, sweating and drooped
      eyelid. The cluster attack was triggered by chewing, shaving and washing the
      face. The periodicity of bouts was six months. The pain was relieved by
      carbamazepine (800 mg/day). The second patient, a 43-year-old man, with an
      excruciant, neuralgic pain in the left side of the face, accompanied by tearing,
      conjuntival injection, drooped eyelid, rhinorrhea, photophobia and phonophobia.
      The neurologic examination showed triggered points in the first and second
      division of the trigeminal nerve. The patient was treated with verapamil (160
      mg/day) and prednisone (60 mg/day), with relief of his symptoms. The periodicity
      of bouts was once a year. The literature was reviewed and 37 cases previosly
      reported are considered. We conclude that there are two different groups of
      patients. In the first group, the patients had cluster and trigeminal bouts in
      different time. In the second group, with only nine cases, the patients presented
      both cluster and trigeminal type of pain at the same time, as in the two cases
      reported here.

PMID- 8984988
TI  - Acute necrotizing myopathy and podophyllin toxicity. Report of a fatal case.
AB  - A 21 year old male ingested podophyllin in a suicide attempt. The disorder was
      marked by seizures, coma, peripheral neuropathy, renal failure and acute
      necrotizing myopathy, an unusual finding. The coma and systemic disturbances
      resolved within three weeks. The myopathy resolved in 7 weeks, demonstrating a
      high capacity of muscle recuperation. The sensorimotor peripheral neuropathy
      persisted until the patient's death 9 weeks after the ingestion, due to
      septicemia. This report confirms the transient central neurotoxicity of
      podophyllin and persistent peripheral neurotoxicity of podophyllin, and describes
      a reversible necrotizing myopathy associated to mitochondrial abnormalities, a
      still unreported feature of podophyllin toxicity.

PMID- 8984989
TI  - Bilateral perisylvian syndrome not related to malformations: report of two cases.
AB  - In this case report we present the neuroimaging findings and clinical features of
      two patients with a bilateral perisylvian syndrome not related to malformations,
      but probably to ischemic etiology. Evaluations including history, general and
      neurologic examinations, electroencephalograms, and imaging data were reviewed as
      recent literature about the subject.

PMID- 8984990
TI  - Giant pseudoaneurysm of the extracranial vertebral artery: case report.
AB  - Pseudoaneurysms of the extracranial vertebral artery are extremely rare due to
      their deep location and the anatomical protection of this artery. They can be
      caused by cervical traumas (firearm injuries, sports, hyperextension of the neck
      and iatrogeny). The authors report the case of a patient who developed a giant
      pseudoaneurysm of the extracranial vertebral artery after surgery for the removal
      of a tumor of the cerebellopontine angle in which surgical lesion of the artery
      occurred. Treatment was performed by endovascular approach. Literature is
      reviewed and comments are made on the physiopathogeny of the lesion and the
      different forms of treatment.

PMID- 8984991
TI  - [Arachnoid cyst and pseudotumor cerebri: case report].
AB  - Report on a 12 years old patient with an arachnoid cyst of posterior cranial
      fossa and pseudotumor cerebri. This patient is a shunt dependent of his cyst
      peritoneal shunt. This association and evolution of this pacient suggest a common
      and specifical pathogenic mechanism of these two pathologies based in a
      disturbance of the cerebral fluid circulation.

PMID- 8984992
TI  - Massive intracranial immature teratoma. Report of a case with polyhidramnios and
      intense pelvic pain.
AB  - A case of massive intracranial immature teratoma in a female stillborn is
      reported. She was the product of the second pregnancy of a 25-year-old healthy
      woman. The pregnancy was unremarkable until the 25th week of gestation when the
      mother noticed a rapid enlargement of her abdomen and intense pelvic pain.
      Because of the pain, a cesarean section was indicated, and a stillborn weighing
      2750g with macrocephaly was delivered. The cranial contents weighed 1350g and
      showed a huge tumoral mass with only a rim of normal brain. A histologic
      diagnosis of immature teratoma was made. Massive intracranial teratomas are rare
      tumors and their occurrence in intrauterine life is even rarer. Their
      histogenesis is unknown, and there is no explanation for their continuous growth
      during embryogenesis. A prenatal diagnosis of this rare condition can be made by
      ultrasound, computed tomography, or magnetic resonance imaging.

PMID- 8984993
TI  - [Aicardi syndrome and choroid plexus papilloma: a rare association. Case report].
AB  - The authors report a case of a 5 months old female child with clinical features
      of Aicardi syndrome: agenesis of the corpus callosum, occular abnormalities
      ("chorioretinal lacunae" and microphthalmus), infantile spasms, mental
      retardation, vertebral malformations and thoracic deformity. The pacient was
      submitted to complementary examinations that confirmed the diagnosis. The
      neuroradiologic images (MRI) showed besides corpus callosum agenesis a tumor
      located at the left ventricular atrium (choroid plexus papilloma). This
      association is a rare occurrence and the present case is the seventh described in
      literature. Furthermore, we suggest that the choroid plexus pappilloma could be a
      characteristic tumor of the Aicardi syndrome.

PMID- 8984994
TI  - [Transverse myelitis as initial symptom of disseminated non-Hodgkin lymphoma and
      HIV-associated vacuolar myelopathy: case report].
AB  - Non-Hodgkin lymphoma is frequently seen in AIDS patients usually affecting the
      central nervous system (CNS), especially the leptomeninges and the cerebral
      hemispheres. The epidural involvement is rarely described, ranging from 3.5% to
      8.3% among the CNS sites. The authors present a case of disseminated non Hodgkin
      lymphoma associated to vacuolar myelopathy in a 27 years-old male patient with
      AIDS emphasizing the importance of this differential diagnosis in the
      myelopathies of AIDS.

PMID- 8984995
TI  - [Cerebral malaria and AIDS: case report].
AB  - Although it has not been definitely proven that the severity of malaria is
      associated to human immunodeficiency virus (HIV) we know that infection through
      Plasmodium falciparum can favor a rapid evolution of the HIV infection. Besides,
      association of malaria with HIV/AIDS from a clinical point of view can be
      clinically severe in the face of the occurrence of other microorganisms or
      neoplasias, which worsens the evolution and prognosis of the affected patients.
      The concurrence of HIV with Plasmodium in malaria endemic zones is a possibility
      which should always be taken into consideration, since transmission is related to
      risk factors caused by people's behavior which are not always promptly revealed
      and/or identified. The authors report one case of brain malaria infection by
      Plasmodium vivax and Plasmodium falciparum in a patient with AIDS. They describe
      the clinical evolution and therapy.

PMID- 8984996
TI  - [Multiple brain abscesses following appendicectomy: case report].
AB  - A 39 years old male patient with a 72 hours evolution of acute abdominal syndrome
      was submitted to appendicectomy. Fourteen days later he developed headache,
      vomiting, aphasia, torpor, nuchal stiffness and right hemiplegia. A CT-scan
      showed multiple brain abscesses on both hemispheres. After aspirative puncture of
      the largest one, antibiotic treatment was established with total recovery of the
      patient.

PMID- 8984997
TI  - Biology of the repair of central nervous system demyelinated lesions: an
      appraisal.
AB  - The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann
      cells respectively in the central nervous system (CNS) and in the peripheral
      nervous system. The process of demyelination consisting of the withdrawal of
      myelin sheaths from their axons is a characteristic feature of multiple
      sclerosis, the most common human demyelinating disease. Many experimental models
      have been designed to study the biology of demyelination and remyelination
      (repair of the lost myelin) in the CNS, due to the difficulties in studying human
      material. In the ethidium bromide (an intercalating gliotoxic drug) model of
      demyelination, CNS remyelination may be carried out by surviving oligodendrocytes
      and/or by cells differentiated from the primitive cell lines or either by Schwann
      cells that invade the CNS. However, some factors such as the age of the
      experimental animals, intensity and time of exposure to the intercalating
      chemical and the topography of the lesions have marked influence on the repair of
      the tissue.

PMID- 8984998
TI  - [Neuropathogenesis of HIV infection].
AB  - The spreading of human immunodeficiency virus (HIV) infection and its increasing
      scientific knowledge keep the medical staff involved with these patients in
      permanent need of updating themselves. The different neurologic manifestations
      caused by HIV are related to a variety of pathogenic mechanisms, as follows:
      immunodeficiency, autoimmunity, direct effects of the virus on the nervous
      system, and toxic and metabolic effects. The opportunistic infections are caused
      by the immunodeficiency due to the action of the virus on CD4+ T cells and on
      cells of the monocytic-macrophage lineage. Demyelinating polyradiculoneuropathy
      and polymyositis-like syndromes are related to autoimmune mechanisms involving,
      probably, the non-specific stimulation of T cells by viral proteins. The primary
      action of the virus on the nervous system brings out aseptic meningitis,
      cognitive dysfunction, dementia, vacuolar myelopathy and sensory polyneuropathy
      probably through liberation of neurotoxic products by the infected macrophages.
      Antiretroviral drugs and others used to treat patients with AIDS may also have
      neurotoxic effects. The better understanding of the neuropathogenesis of HIV
      infection will permit the use of new, and more specific, therapeutical options in
      the future as well as a more precocious control of its neurologic complications.

PMID- 8984999
TI  - [Possible mechanisms of regulating glucose-6-phosphate dehydrogenase activity by
      an excess of substrate and coenzyme].
AB  - The kinetics of glucose 6-phosphate oxidation by glucose 6-phosphate
      dehydrogenase from wheat seeds was studied at pH 6-11 within a broad interval of
      the glucose 6-phosphate and NADH concentrations. A high substrate concentration
      (over 4-6 mM) activated the enzyme within the pH range studied; the excess of
      NADH inhibited glucose 6-phosphate dehydrogenase at pH 6.0-9.5. The enzyme's
      active site groups with pK of 7.2, 8.0, and 9.0 were shown to be involved in the
      substrate binding in the enzyme-substrate complexes. The ionization of the groups
      with pK 8.0 and 9.5 appeared to affect the catalytic activity of the enzyme. The
      deprotonation of the group with pK 9.5 increased the reaction rate, whereas its
      protonation favored enzyme inhibition by high NADH concentrations.

PMID- 8985000
TI  - [Electronic and spatial parameters of antiparallel and parallel double-stranded
      beta-structure of a protein and its associates].
AB  - Calculations of valerolactam and N-methylacetamide dimers by the method of
      molecular orbitals in CNDO/2H, MINDO/3, MINDO/3H, MNDO, MNDO/H, AM1, and PM3
      approximations showed that the PM3 was the most suitable method for the
      description of geometrical and thermodynamic characteristics of hydrogen bonds
      between their amide groups. The calculation of the H-bound dimers of N
      acetylalanine methylamide, which mimicked the beta structure of protein
      macromolecule, showed that the antiparallel conformation of the dimer is by 2.85
      kcal/mol more stable than the parallel conformation. According to the data
      obtained by using the AM1 approximation, the parallel type dimer has the enhanced
      ability to transmit the electron disturbance along the chain of amide-amide
      hydrogen bonds. The formation of the complexes of the antiparallel and the
      parallel types lead to the increase of the H-bonding ability of the outer oxygen
      atom of the amide group in comparison with the monomer.

PMID- 8985001
TI  - [An improved method of preparing protein and peptide probes in mass spectrometry
      with ionization of division fragments by californium-252 (TOF-PDMS)].
AB  - The addition of organic acids (picric, oxalic, citric, or tartaric) to peptide
      and protein samples was found to significantly increase the yield of their quasi
      molecular ions (QMI) in time-of-flight 252Cf plasma desorption mass spectrometry.
      The yield of the ions depended on the pKa of the acid added.

PMID- 8985002
TI  - [Sequential attachment of arginine residues to peptides catalyzed by subtilisin.
      II. Effect of the nature of acylating and nucleophilic components and small
      amounts of water in organic solvents].
AB  - The reaction of Dnp(or Z)-Ala2-Xaa-OCH3 (Xaa = Ile of Val) with arginine amide or
      p-nitroanilide was studied in organic solvents, which was catalyzed by subtilisin
      sorbed on macroporous glass, It resulted in the formation of peptides containing
      one to four arginine residues: Dnp(or Z)-Ala2-Xaa-(Arg) 1-4-NH2. The number of
      arginine residues attached to the peptide depended on the water content in
      organic solvents, nature of the amino acid residue Xaa in the P1 position of the
      acylating component, and the type of the N-protective group. The reaction can be
      used for synthesizing arginine-containing substrates of convertases and
      cathepsins B, L, and O. A chromogenic substrate for duodenase Z-Ala2-Ile-Arg2-pNA
      was obtained.

PMID- 8985003
TI  - [Nucleotide sequence of a fragment of the Cottocomephorus grewingki
      phosphofructokinase gene].
AB  - The nucleotide sequence of a 208-bp fragment of the pfk gene encoding
      phosphofructokinase from Baikalian fish Cottocomephorus grewingki (Cottidae
      family) was determined. The fragment shows the codes of a sequence of 38 amino
      acid residues and contains a 94-bp intron. The nucleotide sequence of the C.
      grewingki phosphofructokinase gene and the corresponding amino acid sequence
      display the maximum homology to phosphofructokinases from rabbit muscles and a
      rat liver.

PMID- 8985005
TI  - Predictability of North Atlantic Multidecadal Climate Variability
AB  - Atmospheric weather systems become unpredictable beyond a few weeks, but climate
      variations can be predictable over much longer periods because of the coupling of
      the ocean and atmosphere. With the use of a global coupled ocean-atmosphere
      model, it is shown that the North Atlantic may have climatic predictability on
      the order of a decade or longer. These results suggest that variations of the
      dominant multidecadal sea surface temperature patterns in the North Atlantic,
      which have been associated with changes in climate over Eurasia, can be predicted
      if an adequate and sustainable system for monitoring the Atlantic Ocean exists.

PMID- 8985004
TI  - [Steryl cellosolves--regulators of cholesterol metabolism in isolated rabbit
      hepatocytes].
AB  - Synthesis of 3 beta-(2-hydroxyethoxy)cholest-5-ene, 3 beta-(2
      hydroxyethoxy)cholest-5-en-7-one, 3 beta-(2-hydroxyethoxy)-7 beta-hydroxycholest
      5-ene, 3 beta-(2-hydroxyethoxy)-5 alpha, 6 alpha-epoxycholestane, and 3 beta-(2
      hydroxyethoxy) -5 alpha, 6 beta-dihydroxycholestane was described. Substances
      obtained inhibited cholesterol biosynthesis in the rabbit hepatocyte cell culture
      with ID 50 from 5.5(+/-0.7) x 10(-8) to 1.3(+/-0.2) x 10(-5) M and also to a
      remarkable extent the cell protein biosynthesis.

PMID- 8985006
TI  - The Origin of Gravitational Lensing: A Postscript to Einstein's 1936 Science
      Paper
AB  - Gravitational lensing, now taken as an important astrophysical consequence of the
      general theory of relativity, was found even before this theory was formulated
      but was discarded as a speculative idea without any chance of empirical
      confirmation. Reconstruction of some of Einstein's research notes dating back to
      1912 reveals that he explored the possibility of gravitational lensing 3 years
      before completing his general theory of relativity. On the basis of preliminary
      insights into this theory, Einstein had already derived the basic features of the
      lensing effect. When he finally published the very same results 24 years later,
      it was only in response to prodding by an amateur scientist.

PMID- 8985008
TI  - The Kinetic Significance of V5 in n-Butane Oxidation Catalyzed by Vanadium
      Phosphates
AB  - Maleic anhydride, a precursor to polyester resins, is made by oxidation of n
      butane over vanadium phosphate catalysts. This system is of general interest
      because it is the only heterogeneously catalyzed, alkane-selective oxidation
      reaction in commercial use. Time-resolved in situ x-ray absorption spectroscopy
      shows that when either alphaI-VOPO4/SiO2 or (VO)2P2O7/SiO2 catalysts are exposed
      to n-butane, the rate of maleic anhydride formation is proportional to the rate
      of decay of V5+ species in the catalyst. Thus V5+ species are kinetically
      significant for the production of maleic anhydride and not just for the
      production of by-products. The results also suggest that V5+ species may play a
      role in the initial hydrogen abstraction from n-butane, the rate-determining step
      in the reaction sequence. V4+ sites appear to be responsible for by-product
      formation.

PMID- 8985007
TI  - Diameter-Selective Raman Scattering from Vibrational Modes in Carbon Nanotubes
AB  - Single wall carbon nanotubes (SWNTs) that are found as close-packed arrays in
      crystalline ropes have been studied by using Raman scattering techniques with
      laser excitation wavelengths in the range from 514.5 to 1320 nanometers. Numerous
      Raman peaks were observed and identified with vibrational modes of armchair
      symmetry (n, n) SWNTs. The Raman spectra are in good agreement with lattice
      dynamics calculations based on C-C force constants used to fit the two
      dimensional, experimental phonon dispersion of a single graphene sheet.
      Calculated intensities from a nonresonant, bond polarizability model optimized
      for sp2 carbon are also in qualitative agreement with the Raman data, although a
      resonant Raman scattering process is also taking place. This resonance results
      from the one-dimensional quantum confinement of the electrons in the nanotube.

PMID- 8985009
TI  - Crustal Deformation from 1992 to 1995 at the Mid-Atlantic Ridge, Southwest
      Iceland, Mapped by Satellite Radar Interferometry
AB  - Satellite radar interferometry observations of the Reykjanes Peninsula oblique
      rift in southwest Iceland show that the Reykjanes central volcano subsided at an
      average rate of up to 13 millimeters per year from 1992 to 1995 in response to
      use of its geothermal field. Interferograms spanning up to 3.12 years also
      include signatures of plate spreading and indicate that the plate boundary is
      locked at a depth of about 5 kilometers. Below that depth, the plate movements
      are accommodated by continuous ductile deformation, which is not fully balanced
      by inflow of magma from depth, causing subsidence of the plate boundary of about
      6.5 millimeters per year.

PMID- 8985010
TI  - Recalibrated Mariner 10 Color Mosaics: Implications for Mercurian Volcanism
AB  - Recalibration of Mariner 10 color image data allows the identification of
      distinct color units on the mercurian surface. We analyze these data in terms of
      opaque mineral abundance, iron content, and soil maturity and find color units
      consistent with the presence of volcanic deposits on Mercury's surface.
      Additionally, materials associated with some impact craters have been excavated
      from a layer interpreted to be deficient in opaque minerals within the crust,
      possibly analogous to the lunar anorthosite crust. These observations suggest
      that Mercury has undergone complex differentiation like the other terrestrial
      planets and the Earth's moon.

PMID- 8985011
TI  - Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent
      pathway.
AB  - Interaction of the p55 tumor necrosis factor receptor 1 (TNF-R1)-associated
      signal transducer TRADD with FADD signals apoptosis, whereas the TNF receptor
      associated factor 2 protein (TRAF2) is required for activation of the nuclear
      transcription factor nuclear factor kappa B. TNF-induced activation of the stress
      activated protein kinase (SAPK) was shown to occur through a noncytotoxic TRAF2
      dependent pathway. TRAF2 was both sufficient and necessary for activation of SAPK
      by TNF-R1; conversely, expression of a dominant-negative FADD mutant, which
      blocks apoptosis, did not interfere with SAPK activation. Therefore, SAPK
      activation occurs through a pathway that is not required for TNF-R1-induced
      apoptosis.

PMID- 8985012
TI  - Regulation of cell cycle synchronization by decapentaplegic during Drosophila eye
      development.
AB  - In the developing Drosophila eye, differentiation is coordinated with
      synchronized progression through the cell cycle. Signaling mediated by the
      transforming growth factor-beta-related gene decapentaplegic (dpp) was required
      for the synchronization of the cell cycle but not for cell fate specification.
      DPP may affect cell cycle synchronization by promoting cell cycle progression
      through the G2-M phases. This synchronization is critical for the precise
      assembly of the eye.

PMID- 8985013
TI  - A synaptically controlled, associative signal for Hebbian plasticity in
      hippocampal neurons.
AB  - The role of back-propagating dendritic action potentials in the induction of long
      term potentiation (LTP) was investigated in CA1 neurons by means of dendritic
      patch recordings and simultaneous calcium imaging. Pairing of subthreshold
      excitatory postsynaptic potentials (EPSPs) with back-propagating action
      potentials resulted in an amplification of dendritic action potentials and evoked
      calcium influx near the site of synaptic input. This pairing also induced a
      robust LTP, which was reduced when EPSPs were paired with non-back-propagating
      action potentials or when stimuli were unpaired. Action potentials thus provide a
      synaptically controlled, associative signal to the dendrites for Hebbian
      modifications of synaptic strength.

PMID- 8985014
TI  - Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs.
AB  - Activity-driven modifications in synaptic connections between neurons in the
      neocortex may occur during development and learning. In dual whole-cell voltage
      recordings from pyramidal neurons, the coincidence of postsynaptic action
      potentials (APs) and unitary excitatory postsynaptic potentials (EPSPs) was found
      to induce changes in EPSPs. Their average amplitudes were differentially up- or
      down-regulated, depending on the precise timing of postsynaptic APs relative to
      EPSPs. These observations suggest that APs propagating back into dendrites serve
      to modify single active synaptic connections, depending on the pattern of
      electrical activity in the pre- and postsynaptic neurons.

PMID- 8985015
TI  - Microtubule treadmilling in vivo.
AB  - In vivo, cytoplasmic microtubules are nucleated and anchored by their minus ends
      at the centrosome and are believed to turn over by a mechanism termed dynamic
      instability: depolymerization and repolymerization at their plus ends. In
      cytoplasmic fragments of fish melanophores, microtubules were shown to detach
      from their nucleation site and depolymerize from their minus ends. Free
      microtubules moved toward the periphery by treadmilling-growth at one end and
      shortening from the opposite end. Frequent release from nucleation sites may be a
      general property of centrosomes and permit a minus-end mechanism of microtubule
      turnover and treadmilling.

PMID- 8985016
TI  - Cancer chemopreventive activity of resveratrol, a natural product derived from
      grapes.
AB  - Resveratrol, a phytoalexin found in grapes and other food products, was purified
      and shown to have cancer chemopreventive activity in assays representing three
      major stages of carcinogenesis. Resveratrol was found to act as an antioxidant
      and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation
      activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and
      hydroperoxidase functions (antipromotion activity); and it induced human
      promyelocytic leukemia cell differentiation (antiprogression activity). In
      addition, it inhibited the development of preneoplastic lesions in carcinogen
      treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse
      skin cancer model. These data suggest that resveratrol, a common constituent of
      the human diet, merits investigation as a potential cancer chemopreventive agent
      in humans.

PMID- 8985017
TI  - Synaptic depression and cortical gain control.
AB  - Cortical neurons receive synaptic inputs from thousands of afferents that fire
      action potentials at rates ranging from less than 1 hertz to more than 200 hertz.
      Both the number of afferents and their large dynamic range can mask changes in
      the spatial and temporal pattern of synaptic activity, limiting the ability of a
      cortical neuron to respond to its inputs. Modeling work based on experimental
      measurements indicates that short-term depression of intracortical synapses
      provides a dynamic gain-control mechanism that allows equal percentage rate
      changes on rapidly and slowly firing afferents to produce equal postsynaptic
      responses. Unlike inhibitory and adaptive mechanisms that reduce responsiveness
      to all inputs, synaptic depression is input-specific, leading to a dramatic
      increase in the sensitivity of a neuron to subtle changes in the firing patterns
      of its afferents.

PMID- 8985018
TI  - Circadian rhythms in rapidly dividing cyanobacteria.
AB  - The long-standing supposition that the biological clock cannot function in cells
      that divide more rapidly than the circadian cycle was investigated. During
      exponential growth in which the generation time was 10 hours, the profile of
      bioluminescence from a reporter strain of the cyanobacterium Synechococcus
      (species PCC 7942) matched a model based on the assumption that cells proliferate
      exponentially and the bioluminescence of each cell oscillates in a cosine
      fashion. Some messenger RNAs showed a circadian rhythm in abundance during
      continuous exponential growth with a doubling time of 5 to 6 hours. Thus, the
      cyanobacterial circadian clock functions in cells that divide three or more times
      during one circadian cycle.

PMID- 8985019
TI  - Combined postoperative radiotherapy and weekly cisplatin infusion for locally
      advanced head and neck carcinoma: final report of a randomized trial.
AB  - PURPOSE: To report the final results of a prospective randomized trial that aimed
      to evaluate efficacy and toxicity of concomitant postoperative radiotherapy and
      Cisplatin infusion in patients with Stage III or IV squamous cell carcinoma of
      the head and neck and histological evidence of extracapsular spread of tumor in
      lymph node metastase(s). METHODS AND MATERIALS: Radiotherapy was delivered using
      a daily dose of 1.7 Gy for the first 54 Gy and 1.8 to 2 Gy until the completion
      of the treatment. Cisplatin 50 mg i.v. with forced hydratation was given or not
      every week (i.e., seven to nine cycles) concurrently with radiotherapy. A total
      of 44 patients were treated by irradiation only (RT group) and 39 by irradiation
      with chemotherapy (CM group). RESULTS: The RT group displayed a higher rate of
      loco-regional failures as compared to CM group (41 vs. 23%; p = 0.08). The
      overall survival, the survival corrected for deaths by intercurrent disease, and
      the disease-free survival were better in CM group as compared to RT group with
      statistically significant differences. Survival without loco-regional treatment
      failure was better in the CM group, the difference being close to the level of
      significance (p = 0.05). Survival without distant metastases were comparable in
      the two therapeutic groups. Ten severe late complications were observed, four in
      the RT group (17%) and six in the CM group (22%). Cox univariate analysis
      confirmed the importance of the therapeutic modality in predicting the overall
      survival, the survival corrected for deaths by intercurrent disease, and the
      disease-free survival. CONCLUSIONS: The present final report of this phase III
      study confirms preliminary results. The concomitant use of 50 mg weekly Cisplatin
      infusion and postoperative radiation improved loco-regional control and survival.
      No significant increase of late radiation complications was observed in the CM
      group.

PMID- 8985020
TI  - Does induction chemotherapy have a role in the management of nasopharyngeal
      carcinoma? Results of treatment in the era of computerized tomography.
AB  - PURPOSE: To assess the outcomes of patients with nasopharyngeal carcinoma (NPC)
      whose treatment was determined by computerized tomography (CT) and/or magnetic
      resonance imaging staging and to analyze the impact of induction chemotherapy and
      accelerated fractionated radiotherapy. METHODS AND MATERIALS: The analysis is
      based on 122 of 143 previously untreated patients with NPC treated with radiation
      therapy at The University of Texas M. D. Anderson Cancer Center between 1983 and
      1992. Excluded were 4 patients treated with palliative intent, 4 children, 12
      patients not staged with CT, and 1 patient who died of a cerebrovascular accident
      prior to completion of treatment. The stage distribution was as follows: AJCC
      Stage I-2, Stage II-7, Stage III-12, Stage IV-101; Tl-15, T2-33, T3-22, T4-52; N0
      32, N1-10, N2-47, N3-32, Nx-1. Fifty-nine (48%) patients had squamous cell
      carcinoma; 63 (52%) had lymphoepitheliomas, undifferentiated NPC or poorly
      differentiated carcinoma, NOS (UNPC). Sixty-seven patients (65 with Stage IV
      disease) received induction chemotherapy. Fifty-eight patients (24 of whom had
      induction chemotherapy) were treated with the concomitant boost fractionation
      schedule. The median follow-up for surviving patients was 57 months. RESULTS: The
      overall actuarial 2- and 5-year survival rates were 78 and 68%, respectively.
      Forty-nine patients (40%) had disease recurrence. Thirty-three (27%) had local
      regional failures; 19 at the primary site only, 8 in the neck and 6 in both.
      Local failure occurred in 31% of patients staged T4 compared to 13% of T1-T3 (p =
      0.007). Sixteen patients failed at distant sites alone. Among Stage IV patients
      the 5-year actuarial rates for patients who did and did not receive induction
      chemotherapy were as follows: overall survival: 68 vs. 56% (p = 0.02), freedom
      from relapse: 64 vs. 37% (p = 0.01), and local control: 86 vs. 56% (p = 0.009).
      The actuarial 5-year distant failure rate in patients with UNPC who were treated
      with induction chemotherapy and controlled in the primary and neck was 13%. In
      patients who did not receive chemotherapy, the actuarial 5-year local control
      rates for patients treated with concomitant boost or conventional fractionation
      were 66 and 67%, respectively. CONCLUSIONS: While not providing conclusive
      evidence, this single institution experience suggests that neoadjuvant
      chemotherapy for Stage IV NPC patients improves both survival and disease
      control. Recurrence within the irradiated volume was the most prevalent mode of
      failure and future studies will evaluate regimens to enhance local regional
      control.

PMID- 8985021
TI  - Advanced carcinoma of the larynx: results of surgery and radiotherapy without
      induction chemotherapy (1980-1985): a multivariate analysis.
AB  - PURPOSE: Induction chemotherapy has been proposed in the case of advanced
      laryngeal cancer in order to preserve laryngeal function in those patients who
      are complete responders. To clarify the treatment policies, a retrospective
      multicentric analysis of 116 patients with advanced carcinoma of the larynx
      treated by radical surgery and postoperative radiotherapy was carried out in
      order to evaluate prognostic factors for local control and survival. METHODS AND
      MATERIALS: Between 1980 and 1985, 116 patients with Stage III squamous cell
      carcinoma of the larynx underwent radical surgery and postoperative radiotherapy
      with a curative intent. Treatments were very homogenous, and doses delivered were
      in the range of 50-65 Gy according to nodal involvement and surgical margins
      status. RESULTS: The local recurrence rate and the local disease-free survival
      rate at 5 years were 22.5% and 76.3%, respectively. Actuarial survival at 5 years
      was 68.3% with 44 patients still alive with no evidence of disease (NED) with
      more than 5 years follow-up. For both overall survival and relapse-free survival,
      cervical node involvement with capsular rupture was found to be the only
      significant adverse pronostic factor in univariate and multivariate analysis. No
      other parameter was predictive either for local recurrence or for survival.
      CONCLUSIONS: Local prognosis and survival depend largely on nodal involvement and
      capsular rupture while increasing doses of radiation strategy is likely to reduce
      the risk of local and nodal recurrence. Preservation of functional larynx is
      certainly an important goal to achieve when treating advanced carcinoma of the
      larynx, provided that local failure rate and survival be similar. In the unique
      randomized study previously published in the literature comparing radical surgery
      and postoperative radiotherapy to induction chemotherapy and radiotherapy, the
      local-regional failure rate was drastically increased in the chemotherapy arm.
      Other results from well-designed controlled studies are awaited before
      recommending systematic induction chemotherapy and larynx preservation in
      complete responders. On the other hand, testing synchronous or alternated
      chemotherapy vs. induction chemotherapy may address the pending questions about
      the optimal treatment of advanced laryngeal carcinoma.

PMID- 8985022
TI  - The role of brachytherapy in early-stage nasopharyngeal carcinoma.
AB  - PURPOSE: To present the treatment results and assess the optimal radiation dose
      and the role of brachytherapy in early stage nasopharyngeal cancer (NPC). METHODS
      AND MATERIALS: One hundred eighty-three patients with Stage I and II (American
      Joint Committee on Cancer Staging System, 1987) NPC completed the planned
      radiotherapy in our institution from 1979 to 1991. In 133 patients, radiotherapy
      was given to the nasopharynx by external beam to 64.8-68.4 Gy. Further boost was
      done by high dose rate (HDR) brachytherapy for 5-16.5 Gy in one to three
      fractions. For the remaining 50 patients, a course of external radiotherapy to
      the nasopharynx for 68.4-72 Gy was given to nasopharynx. Age (>40 or not), sex,
      neck boost or not, brachytherapy, and irradiation dose were analyzed to determine
      significant factors that influence the probabilities of local control and
      actuarial survival. RESULTS: The 5-year disease-specific survival was 85.8% and
      local control was 83%. Only the brachytherapy and irradiation dose significantly
      affected the results. The use of the brachytherapy had significant impact on
      overall survival and local control. Furthermore, we compared the prognostic
      effect of various radiation dosage among Group I of 50 patients (<72.5 Gy, no
      brachytherapy, excluding four patients who received brachytherapy), Group II of
      71 patients (72.5-75 Gy; one to two fractions of brachytherapy), and Group III of
      58 patients (>75 Gy; three fractions of brachytherapy). Five-year disease
      specific survival rates of Group I, Group II, and Group III were 77, 95.5, and
      82.4%, respectively. Five-year local control rates were: 73.7, 93.9, and 79.5%.
      We found that the Group II had the best actuarial survival and local control rate
      (log-rank test,p < 0.05). Most patients receiving brachytherapy encountered foul
      odor because of nasopharynx crust; 12 of them had palate or sphenoid sinus floor
      perforation or nasopharynx necrosis. None of the patients without brachytherapy
      experienced the same complications. CONCLUSIONS: The optimal radiotherapy dose to
      the nasopharynx area in early stage NPC may be within 72.5 to 75 Gy by our
      treatment protocol. A dose of more than 75 Gy did not have significant local
      control or survival advantage. The use of brachytherapy to elevate radiation dose
      had significant local control and survival benefit for early stage NPC patients,
      but the fractionation size should be decreased to reduce the complications.

PMID- 8985023
TI  - Early glottic cancer: the influence of primary treatment on voice preservation.
AB  - PURPOSE: Retrospective analysis was performed to assess the influence of primary
      surgical or irradiation treatment on local control, survival, and final
      preservation of larynx in comparable groups of patients with T1N0 and T2N0
      glottic cancer. METHODS AND MATERIALS: Two hundred sixty-three previously
      untreated patients with invasive squamous cell carcinoma of the glottis (187T1
      and 76T2) were treated with primary radiotherapy (159T1 and 60T2) or primary
      surgery (28T1 and 16T2) between January 1976 and December 1990, at the University
      of Ljubljana, Slovenia. Conventional one daily fraction of 2 Gy to doses of 60-74
      Gy (median: 65 Gy) were used in 98% of primarily irradiated patients through out
      the observed period. To enable better comparison between the two treatment
      groups, primarily irradiated patients were retrospectively stratified by the
      criteria of suitability for primary voice-sparing operation. Several host, tumor,
      and treatment parameters were analyzed. RESULTS: Only the stage of the disease
      significantly influenced both 10-year recurrence-free and disease-specific
      survival regardless primary treatment modality (p = 0.0002). In all primary
      irradiated patients local control was significantly better for those with overall
      treatment time of less than 48 days (p = 0.007). In patients suitable for voice
      sparing operation, local control of primarily operated patients was similar to
      that of patients primarily irradiated with shorter overall treatment time, which
      was 93 and 88% for T1 and 67 and 64% for T2 tumors, respectively. Ultimate local
      control in primary surgery and radiotherapy group was 96 and 96% for T1 and 89
      and 88% for T2 tumors, respectively. Equal larynx preservation of 100% in T1 and
      90% in T2 patients was achieved in finally cured primarily operated patients and
      those patients primarily irradiated with a shorter overall treatment time. If
      treatment time was longer than 48 days, significantly worse final larynx
      preservation of 84% in T1 and 75% in T2 patients was observed (p = 0.003). In
      patients unsuitable for voice sparing operation, 87% of T1 and 50% of T2 patients
      in primary radiotherapy group finally had their larynx preserved. CONCLUSION:
      Stratification based on criteria of possibility for initial voice-sparing
      operation is important when comparing primary surgery with primary radiotherapy
      treatment in early glottic cancer. The detrimental effect of prolonged treatment
      time of irradiation resulted not only in inferior local control rate but also in
      worse final larynx preservation.

PMID- 8985024
TI  - Necrosis following radiotherapy for carcinoma of the pinna.
AB  - PURPOSE: Radiation therapy is often the preferred modality of treatment for
      carcinoma of the pinna because it avoids the cosmetic defect of surgery. However,
      radiation oncologists are sometimes reluctant to irradiate the ear because of the
      risk of subsequent necrosis. The goal of this study was to establish the long
      term disease control and necrosis rates following irradiation of the external
      ear. METHODS AND MATERIALS: A retrospective analysis was undertaken of 138
      courses of curative radiotherapy given to 128 patients for biopsy-proven basal
      (70 courses), squamous (62 courses), or mixed (6 courses) tumors of the pinna
      between January 1, 1982, and December 31, 1991, at the Kingston Regional Cancer
      Center. RESULTS: The median age of the patients was 73 (range 43-94) and the
      median size of the tumors was 12 mm (range 3-50 mm). Treatment was given using
      orthovoltage X rays (79) or electrons (59). The most common dose prescription was
      35 Gy/5 fractions; total doses ranged from 17.50 to 64 Gy. The median follow-up
      is 58 months (range 6-149). The actuarial 5-year local control rate is 93%; the
      actuarial necrosis rate at 5 years is 13%. Most necroses healed with conservative
      management; only two patients required surgery for necrosis. We analyzed the
      following factors as possible predictors of radiation necrosis: patient age, size
      of lesion, histology, fraction size, total dose, overall time, and beam energy.
      Only daily fraction sizes > 6 Gy (p = 0.0093) and treatment times < 5 days (p =
      0.0053) were significantly associated with an increased risk of necrosis.
      CONCLUSION: To reduce the risk of necrosis, radiation therapy for external ear
      cancer should be given using protracted fractionation.

PMID- 8985025
TI  - The impact of surgical margin status and use of an interstitial implant on T1, T2
      oral tongue cancers after surgery.
AB  - PURPOSE: In patients with T1,T2 oral tongue carcinoma treated with surgical
      resection, postoperative radiation therapy (RT) is required especially when
      surgical margins contain tumors. Irradiation techniques include external beam,
      interstitial implants, or a combination of the two modalities. We investigated
      whether positive surgical margin remains a poor prognostic factor after radiation
      therapy, and the contribution of interstitial implants to disease control.
      METHODS AND MATERIALS: Between 1972 and 1989, 55 patients were treated
      postoperatively at the Mallinckrodt Institute of Radiology for T1,T2 squamous
      cell carcinomas of the oral tongue. Surgeries included 26 wide excisions or
      excisional biopsies and 29 composite resections or hemiglossectomies. Thirty-nine
      patients received external radiation therapy alone and 16 patients had an
      interstitial implant (ISI) as part of the treatment. The minimum follow-up is 4
      years. RESULTS: At 2 and 5 years, the overall survivals for all patients were 82
      and 68%. The disease-free survivals (DFS) were 82 and 70%, respectively. There
      was no significant difference in the pattern of failure and DFS when stratified
      by the status of surgical margins and the type of the surgical procedure. Local
      control was achieved in 15 of 18 patients when surgical margins were involved by
      tumor and in 29 of 37 patients without tumor involving margins (p > 0.05). Ten of
      18 (56%) patients with tumor involving resection margins were treated with ISI,
      whereas only 3 of 33 (9%) of those with negative margins received ISI. Local
      control was achieved in 32 of 39 patients treated with external beam RT alone,
      and 13 of 16 patients who received interstitial implant (p > 0.05). Four patients
      treated with ISI developed persistent soft tissue ulceration and mandibular bone
      exposures. CONCLUSIONS: Postoperative radiation therapy converted the ominous
      outcome of patients with tumor involving surgical margins. Patients with positive
      surgical margins were often selected to be treated with interstitial implants. We
      found that the local control was as good as in those with a more favorable
      pathology (negative margins) and treated with external RT alone. Further
      investigation is needed to optimize the implant treatment to minimize the
      complications.

PMID- 8985026
TI  - Gamma knife for glioma: selection factors and survival.
AB  - PURPOSE: To determine factors associated with survival differences in patients
      treated with radiosurgery for glioma. METHODS AND MATERIALS: We analyzed 189
      patients treated with Gamma Knife radiosurgery for primary or recurrent glioma
      World Health Organization (WHO) Grades 1-4. RESULTS:  CONCLUSION: The median
      minimum tumor dose was 16 Gy (8-30 Gy) and the median tumor volume was 5.9 cc
      (1.3-52 cc). Brachytherapy selection criteria were satisfied in 65% of patients.
      Median follow-up of all surviving patients was 65 weeks after radiosurgery. For
      primary glioblastoma patients, median survival from the date of pathologic
      diagnosis was 86 weeks if brachytherapy criteria were satisfied and 40 weeks if
      they were not (p = 0.01), indicating that selection factors strongly influence
      survival. Multivariate analysis showed that increased survival was associated
      with five variables: lower pathologic grade, younger age, increased Karnofsky
      performance status (KPS), smaller tumor volume, and unifocal tumor. Survival was
      not found to be significantly related to radiosurgical technical parameters
      (dose, number of isocenters, prescription isodose percent, inhomogeneity) or
      extent of preradiosurgery surgery. We developed a hazard ratio model that is
      independent of the technical details of radiosurgery and applied it to reported
      radiosurgery and brachytherapy series, demonstrating a significant correlation
      between survival and hazard ratio. CONCLUSIONS: Survival after radiosurgery for
      glioma is strongly related to five selection variables. Much of the variation in
      survival reported in previous series can be attributed to differences in
      distributions of these variables. These variables should be considered in
      selecting patients for radiosurgery and in the design of future studies.

PMID- 8985027
TI  - Risk analysis of linear accelerator radiosurgery.
AB  - PURPOSE: To evaluate the toxicity of stereotactic single-dose irradiation and to
      compare the own results with already existing risk prediction models. METHODS AND
      MATERIALS: Computed tomography (CT) or magnetic-resonance (MR) images, and
      clinical data of 133 consecutive patients treated with linear accelerator
      radiosurgery were analyzed retrospectively. Using the Cox proportional hazards
      model the relevance of treatment parameters and dose-volume relationships on the
      occurrence of radiation-induced tissue changes (edema, localized blood-brain
      barrier breakdown) were assessed. RESULTS: Sixty-two intraparenchymal lesions
      (arteriovenous malformation (AVM): 56 patients, meningioma: 6 patients) and 73
      skull base tumors were selected for analysis. The median follow-up was 28.1
      months (range: 9.0-58.9 months). Radiation-induced tissue changes (32 out of 135,
      23.7%) were documented on CT or MR images 3.6-58.7 months after radiosurgery
      (median time: 17.8 months). The actuarial risk at 2 years for the development of
      neuroradiological changes was 25.8% for all evaluated patients, 38.4% for
      intraparenchymal lesions, and 14.6% for skull base tumors. The coefficient: total
      volume recieving a minimum dose of 10 Gy (VTREAT10) reached statistical
      significance in a Cox proportional hazards model calculated for all patients,
      intraparenchymal lesions, and AVMs. In skull base tumors, the volume of normal
      brain tissue covered by the 10 Gy isodose line (VBRAIN10) was the only
      significant variable. CONCLUSIONS: These results demonstrate the particular
      vulnerability of normal brain tissue to single dose irradiation. Optimal
      conformation of the therapeutic isodose line to the 3D configuration of the
      target volume may help to reduce side effects.

PMID- 8985028
TI  - Prognostic factors for acute and late skin reactions in radiotherapy patients.
AB  - PURPOSE: Patients treated with identical radiotherapy schedules show a
      substantial variation in the degree of acute and late normal tissue reactions. To
      identify any possible contributing factors to this phenomenon, we have analyzed
      the treatments of 402 breast cancer patients. METHODS AND MATERIALS: The patients
      received adjuvant postoperative radiotherapy between 1972 and 1985 and have been
      followed up since then. Multivariate analyses were performed with peak
      reflectance erythema and peak acute reaction score as endpoints for the acute
      reactions, and with progression rate of telangiectasia as well as telangiectasia
      score as endpoints for the late reactions. Twenty patient- and treatment-related
      factors were tested such as age, menopausal status, hemoglobin level, serum
      calcium, smoking habits, hypothyroidism, diabetes, hypertension, blood pressure,
      cardiovascular and autoimmune disease, the influence of hormone therapy and
      chemotherapy, pretreatment reflectance value, acute skin reactions, radiation
      quality, individual dose, bilateral fields, and the total effect (TE) for the
      dose schedule applied. RESULTS: The TE was a strong prognostic factor for all
      endpoints. In addition to TE, blood pressure was prognostic for the peak erythema
      measured by reflectance spectrophotometry, and the pretreatment reflectance value
      was prognostic for the acute score. The only independent prognostic factors found
      for the progression of skin telangiectasia and telangiectasia score except for TE
      were the individual dose and the acute skin reactions. CONCLUSIONS: These factors
      explained at most about 30% of the variance describing the total patient-to
      patient variability for each endpoint. The remaining variability is still
      unexplained but may be related to individual differences in cellular
      radiosensitivity, partly determined by genetic variations and partly by unknown
      epigenetic factors.

PMID- 8985029
TI  - Radiotherapy vs. radiotherapy and razoxane in the treatment of soft tissue
      sarcomas: final results of a randomized study.
AB  - PURPOSE: The effect of the sensitizer razoxane on soft tissue sarcomas (STS) was
      prospectively evaluated in a randomized, controlled trial. The main purpose of
      the study was to determine the response rates and local control under the
      combined treatment compared to irradiation alone. METHODS AND MATERIALS: Between
      1978 and 1988, 144 patients entered the study; 130 were evaluable for response,
      toxicity, or survival. The patients were randomized to receive radiotherapy alone
      or radiotherapy with razoxane. They were divided into postoperative cases and
      patients with gross disease (unresectable primaries, recurrent disease, or
      metastatic disease). The median radiation dose was 60 Gy postoperatively, and 56
      58 Gy in patients with gross disease. The dose difference has palliative reasons.
      Razoxane was given orally at a daily dose of 150 mg/m2 during the time of the
      radiotherapy, starting 5 days before the first irradiation. In general, the
      groups were comparable as to their prognostic factors. There was some imbalance,
      however, in favor of the postoperative group reveiving radiotherapy alone.
      RESULTS: Between the patient groups treated postoperatively in an adjuvant form,
      there were no substantial differences in local control and survival. Among 82
      patients with gross disease, the treatment with radiotherapy and razoxane led to
      an increased response rate compared to photon irradiation alone (74 vs. 49%). The
      local control rate was likewise improved (64 vs. 30%;p < 0.05). The acute
      toxicity was somewhat higher in the sensitizer arm, but there was no difference
      in the occurrence of late complications. CONCLUSIONS: Radiotherapy combined with
      razoxane seems to improve the local control in inoperable, residual, or recurrent
      STS compared to radiotherapy alone. The combined treatment is a fairly well
      tolerated procedure at low costs. It can be recommended for inoperable primary
      STS or gross disease after incomplete resection, conditions which are still
      associated with limited local control and a grave prognosis.

PMID- 8985030
TI  - Rapid course radiation therapy vs. more standard treatment: a randomized trial
      for bone metastases.
AB  - PURPOSE: In a prospective randomized trial we examined whether radiotherapy of
      painful bone metastases can be shortened using larger single doses without
      impairing effectivity. METHODS AND MATERIALS: One hundred patients with painful
      bone metastases having no prior surgical intervention or treatment with x-ray
      therapy and had a median follow-up of 12 months were analyzed. The primary tumor
      was located in the breast in 43%, in the lung in 24%, and in the prostate in 14%.
      The most frequent sites of metastases were the pelvis (31%), the vertebral column
      (30%), and the ribs (20%). Further percentages of sites were: lower extremity
      11%, upper extremity 6%, and skull 2%. Fifty-one patients received a short course
      radiotherapy with a total dose of 20 Gy in 1 week (daily dose 4 Gy), and 49
      patients received 30 Gy in 3 weeks (daily dose 2 Gy). RESULTS: There were no
      significant differences in frequency, duration of pain relief, improvement of
      mobility, recalcification, frequency of pathologic fractures nor survival. There
      was a light trend favoring 30 Gy in frequency of pain relief and recalcification.
      Survival was mostly influenced by primary tumor site, Karnofsky performance
      status, and possibly by the response to radiotherapy (pain relief). CONCLUSIONS:
      Because of the very short life expectancy of patients with metastatic bone
      disease, we now use 20 Gy in 1 week as our standard to reduce hospital stay.

PMID- 8985031
TI  - Optimal size criteria of malignant lymph nodes in the treatment planning of
      radiotherapy for esophageal cancer: evaluation by computed tomography and
      magnetic resonance imaging.
AB  - PURPOSE: To determine the optimal size criterion for detection of lymph node
      metastases from esophageal cancer for radiotherapy by computed tomography (CT)
      and magnetic resonance (MR) imaging. METHODS AMD MATERIALS: In 58 patients with
      esophageal cancer treated with subtotal esophagectomy and radical lymph node
      dissection the preoperative MR (n = 58) images and CT scans (n = 41) were
      reviewed. The relationship of the CT and MR findings for the neck and mediastinum
      to the surgical and histopathological results was examined. Five size criteria on
      malignant lymph nodes were used to construct receiver operating characteristic
      (ROC) curves for CT and MR, and their detectabilities were evaluated. RESULTS:
      The specificities of both modalities at the cutoff of 3 mm short-axis diameter
      were lower than those at the cutoff of 5 mm or more. In contrast, the
      sensitivities apparently decreased at the cutoff of 10 mm or more. The analysis
      of the ROC curves showed that the optimal size criterion for malignant lymph
      nodes was 5 mm for both CT and MR. When the criterion of 5 mm was used, the
      sensitivity, specificity, and accuracy for CT was 68, 92, and 87%, respectively,
      and the respective values for MR were 70, 93, and 89%. Although there was no
      significant difference between the two ROC curves, MR was useful in
      distinguishing lymph nodes from vascular structures because of the flow void.
      CONCLUSIONS: There was no significant difference between CT and MR in the
      detection of malignant lymph nodes from esophageal cancer. The optimal size
      criterion for both CT and MR in the detection of cervical and mediastinal lymph
      node metastases is 5 mm for short-axis diameter. These results suggest that all
      regional lymph nodes of 5 mm or more on CT or MR should be regarded as part of
      the gross tumor volume in the treatment planning of radiotherapy for esophageal
      cancer.

PMID- 8985032
TI  - Preferential radiosensitization of G1 checkpoint-deficient cells by
      methylxanthines.
AB  - PURPOSE: To develop a checkpoint-based strategy for preferential
      radiosensitization of human tumors with deficient and/or mutant p53. METHODS AND
      MATERIALS: A549 human lung adenocarcinoma cell lines differing in their
      expression of the p53 tumor suppressor gene were produced by transduction with
      the E6 oncogene from human papilloma virus type 16. The cells expressing E6 (E6+)
      lack a G1 arrest in response to ionizing radiation, are deficient in p53 and p21
      expression, and exhibit a fivefold greater clonogenic survival following 10 Gy
      radiation. RESULTS: Postirradiation incubation with millimolar concentrations of
      the methylxanthine pentoxifylline (PTX) results in preferential
      radiosensitization of the E6+ cells compared to the LXSN+ vector transduced
      controls. There is a threefold sensitization of the LXSN+ cells and a 15-fold
      sensitization of the E6+ cells, which results in equal clonogenic survival of the
      two lines. Flow cytometry reveals PTX abrogation of the radiation induced G2
      arrest for both cell lines. PTX also prolongs G1 transit for both cell lines.
      Preliminary results are presented using a novel methylxanthine, lisofylline
      (LSF), which has similar cell cycle effects on G1 and G2 and achieves
      differential radiosensitization at micromolar concentrations that are sustainable
      in humans. CONCLUSION: This checkpoint-based strategy is a promising approach for
      achieving preferential radiosensitization of p53- tumors relative to p53+ normal
      tissues.

PMID- 8985033
TI  - Evaluation of the radiosensitizing effects of RK28 intravenous, intraarterial,
      and intratumoral injections on the rabbit VX2 tumor system.
AB  - PURPOSE: To evaluate the differences in the radiosensitizing effects of
      intravenous (i.v.) injection, intraarterial (i.a.) injection, and intratumoral
      (i.t.) injections of the hypoxic cell radiosensitizer RK28 ([1-(4'-hydroxy-2'
      butenoxy)methyl-2-nitroimidazole], a 2-nitroimidazole with an acyclic sugar
      analogue substituted at the N-1 position of the imidazole ring) using an animal
      experimental system. METHODS AND MATERIALS: Rabbit VX2 tumors, which were
      implanted in the muscle of left hind legs and grown to 3 cm in diameter, were
      treated with RK28 (80 mg/kg x b.wt.) before 15 Gy of local x-ray irradiation. The
      auricular vein and the left saphenous artery were used for systemic injection and
      regional injection, respectively. For i.t. injection, a 21-gauge needle with
      three lateral holes was positioned in the central area of the tumor. Tumor
      regression was precisely evaluated by computed tomograpy (CT), and survival time
      was also studied. Using high-performance liquid chromatography (HPLC),
      pharmacokinetic studies for RK28 and its seven major metabolites were performed
      in tumor and serum at 0, 10, 20, 30, and 60 min after drug injection was
      completed. RESULTS: Radiosensitizing effects of RK28 were considered present
      after i.a. injection (p < 0.05) and i.t. injection (p < 0.05) after analyzing
      tumor volumes on day 21 after treatment. Increased survival was not observed in
      any group with RK28 injection compared with survival in the group treated by x
      ray irradiation alone. Pharmacokinetic studies showed the average concentration
      of RK28 in the tumor during x-ray irradiation was 1.3 times higher after i.a.
      injection and 3.5 times higher after i.t. injection than that after i.v.
      injection. The time modifying factor50 (TMF50: ratio of time for tumor to
      decrease by 50%, radiation alone vs. radiation plus drug) was calculated to be
      1.5 after i.v. injection, 1.7 after i.a. injection, and 2.3 after i.t. injection.
      The values of TMF50 correlated to the average concentrations of RK28 in the
      tumor. As to metabolites of RK28, beta-glucuronated compound and cysteine
      conjugate were highly detected. The concentrations of cysteine conjugate were
      higher in the tumor than in serum via i.v. injection. CONCLUSIONS:
      Radiosensitizing effects of RK28 were observed on the rabbit VX-2 tumor system
      after i.a. or i.t. injection. Pharmacokinetic studies proved that
      radiosensitizing effects depended on the concentration in the tumor, though the
      administration routes were different. Combined forms with nonprotein thiols were
      detected. However, survival benefits were not obtained by RK28. For clinical
      applications of RK28, i.a. or i.t. injection could facilitate better local
      control of cancer.

PMID- 8985034
TI  - Selective tumor irradiation by infusional brachytherapy in nonresectable
      pancreatic cancer: a phase I study.
AB  - PURPOSE: Selective high-dose radiation of solid tumors has been a goal of
      radiation oncology. The physiological barriers of solid tumors (high interstitial
      tumor pressure, reduced tumor vascularity, and poor perfusion) have been major
      barriers in achieving significant tumor dose of systemically infused
      radioconjugates. Direct tumor infusional brachytherapy overcomes these barriers
      and leads to selective high tumor doses. METHODS AND MATERIALS: The development
      of interstitial tumor infusion of macroaggregated albumin (MAA) followed by
      colloidal chromic phosphate 32P has overcome solid tumor obstacles in 47 patients
      with nonresectable pancreatic cancer in a Phase I dose escalation study. The
      colloidal 32P infusion was followed by external radiation and five fluorouracil.
      RESULTS: Of the 28 patients with cancer limited to the pancreas, 15 of 16
      patients retained 86-100% (mean 96%) of the infused colloidal 32P isotope. While
      the other 12 patients had partial shunting to the liver, shunting to the liver
      was due to high interstitial resistance with tumor dose deposition of 17-88%
      (mean 52 %). Of the 19 patients with metastatic pancreas cancer, colloidal 32P
      tumor deposition ranged from 22 to 100% of the infused dose (mean 79%). The less
      than optimal tumor deposition led to our increasing the MAA from 600,000 to 1.5
      2.5 million particles. Interstitial dexamethasone 2 mg and later 4 mg was infused
      first and prevented liver shunting by somehow reducing tumor resistance. The
      median survival in 28 Phase I patients with nonresectable pancreas cancer without
      metastasis, was 12 months. No significant toxicity occurred when treatment was
      limited to two infusions with as much as 30 mCi each. The maximum tumor dose was
      17,000 Gy (1.700,000 cGy). In 19 nonresectable pancreatic cancer patients with
      metastasis, a 6.9 months median survival was observed. CONCLUSIONS: Infusional
      brachytherapy is an outpatient procedure that delivers high-dose radiation
      selectively to pancreatic cancer. Results of the Phase I study in nonresectable
      pancreas cancer has led to a national multiinstitutional Phase II trial.

PMID- 8985035
TI  - Partially hyperfractionated accelerated radiotherapy and concurrent chemotherapy
      for advanced nasopharyngeal carcinoma.
AB  - PURPOSE: A newly designed concomitant chemoradiotherapy was undertaken to assess
      the feasibility and efficacy for advanced nasopharyngeal carcinoma (NPC). METHODS
      AND MATERIALS: Sixty-three patients with biopsy-proven NPC were entered in this
      Phase II trial from March 1992 to November 1993. Most patients present with Stage
      IV disease (93.4%) and poorly differentiated epidermoid carcinoma or
      undifferentiated carcinoma were the major pathologic type. Radiotherapy was
      delivered using a telecobalt unit and 10 MV x-rays and by altered fractionation
      (72-74 Gy/45 fractions/6 weeks). Chemotherapy with cisplatin 75 mg/m2, 2 h
      infusion at day 1, followed by 5-FU 400 mg/m2/day, continously infused for 4 days
      was given concurrently during the first and fifth weeks of radiotherapy. RESULTS:
      The major toxicity was mucositis (61% belong to Grade 3, 31% to Grade 2). Weight
      loss, leucopenia, and skin reaction were frequently encountered. Three patients
      withdrew from treatment at 15, 25, and 55.5 Gy, three patients interrupted the
      radiotherapy for 1-4.5 weeks, and two patients refused the second cycle of
      concomitant chemotherapy due to toxicities. The initial tumor response showed
      100% overall response rate, with 90.5% complete response. After a median follow
      up time of 38 months, five patients failed at the primary and/or neck (four
      recurrent and one persistent), and 14 patients developed distant metastases
      alone. The 3-year primary disease-free, regional disease-free, distant disease
      free, and overall survival rates are 89.1, 92.8, 74.3, and 73.6%, respectively.
      The late complication rate is acceptable so far. CONCLUSIONS: Our data indicates
      that concurrent chemoradiotherapy for advanced NPC is both feasible and
      effective, with acceptable toxicities. Distant metastases are the major site of
      treatment failure. Postradiation adjuvant chemotherapy to eradicate subclinical
      distant metastasis should be further studied.

PMID- 8985036
TI  - Accelerated radiation therapy for locally advanced squamous cell carcinomas of
      the oral cavity and oropharynx selected according to tumor cell kinetics--a phase
      II multicenter study.
AB  - PURPOSE: A Phase II multicenter trial testing an accelerated regimen of
      radiotherapy in locally advanced and inoperable cancers of the head and neck, in
      patients selected on the basis of 5-bromo-2-deoxyuridine/DNA flow cytometry
      derived tumor potential doubling time (Tpot). METHODS AND MATERIALS: From
      September 1992 to September 1993, 23 patients consecutively diagnosed to have
      locally advanced, inoperable carcinomas of the oral cavity and the oropharynx,
      with Tpot of < or = 5 days, received an accelerated radiotherapy regimen (AF)
      based on a modification of the concomitant boost technique: 2 Gy/fraction once a
      day, delivered 5 days a week up to 26 Gy, followed by 2 Gy/fraction twice a day,
      with a 6-h interval, one of the two fractions being delivered as a concomitant
      boost to reduced fields, up to 66 Gy total dose (off-cord reduction at 46 Gy),
      shortening the overall treatment time to 4.5 weeks. A contemporary control group
      of 46 patients with Tpot of >5 days or unknown was treated with conventional
      fractionation (CF): 2 Gy/fraction once a day, 5 days a week, up to 66 Gy in 6.5
      weeks, with fields shrinkage after 46 Gy. RESULTS: All patients completed the
      accelerated regimen according to protocol and in the prescribed overall treatment
      time. Immediate tolerance was fairly good: 65% of the patients in the AF group
      experienced Grade 3 mucositis vs. 45% in the CF group (p = n.s.). Symptoms
      related to mucosal reactions seemed to persist longer in AF than in CF patients.
      The crude proportion of mild (Grades 1 and 2) late effects on skin (p < 0.01) and
      salivary glands (p < 0.05) was higher in AF than in CF patients, although these
      reactions did not exceed the limits of tolerance. Three patients in the AF and 1
      in the CF arm experienced a late Grade 4 bone complication. Actuarial estimates
      of severe (Grades 3 and 4) late complications showed a 2-year hazard of 33.3% in
      the AF arm and 49.7% in CF (p = NS). The actuarial 2-year local control rate of
      the AF patients was 49.4%, while actuarial 2-year overall survival for the same
      patients was 43.5%. CONCLUSION: The results suggested that this accelerated
      regimen is worth testing in a controlled randomized trial to compare different
      accelerated schedules. Our findings also confirmed the 5-bromo-2-deoxyuridine/DNA
      flow cytometry technique as a suitable method of evaluating tumor cell kinetics
      in multicenter clinical studies, on condition that all measurements are carried
      out by one most experienced laboratory.

PMID- 8985037
TI  - Postoperative radiotherapy for head and neck squamous cell carcinomas:
      feasibility of a biphasic accelerated treatment schedule.
AB  - PURPOSE: It has been suggested that postoperative tumor cell proliferation may
      influence the outcome of advanced head and neck squamous cell carcinomas treated
      by surgery and postoperative radiotherapy. This Phase I pilot study was
      undertaken to determine the feasibility of a biphasic accelerated radiotherapy
      regimen with early and late concomitant boost delivery for postoperative
      treatment of patients with advanced head and neck cancers. METHODS AND MATERIALS:
      From April 1993 to April 1994, 29 patients with advanced head and neck cancers
      were enrolled in this study after they underwent complete surgical resection. The
      basic radiation course delivered a median dose of 49 Gy in 25 fractions over 5
      weeks at 1.8-2 Gy/fraction. The concomitant boost was delivered to the high-risk
      areas as a second daily fraction during the first (1.4 Gy/fraction) and fifth
      weeks (1.6 Gy/fraction). The total dose to the high-risk areas was 64 Gy in 35
      fractions over 5 weeks. RESULTS: Twenty-seven patients (93%) completed the
      treatment without interruptions. Only two patients experienced severe acute
      toxicity requiring treatment breaks of 6 and 8 days, respectively. All patients
      developed confluent mucositis; in 69% of the cases it covered >50% of the treated
      surface. No patient developed Grade 5 (ulceration/bleeding) mucosal reaction.
      Mucositis required a median time of 7 weeks for complete healing (range 3-43).
      Two patients developed transient bone exposure. The median weight loss was 5.5%
      of pretreatment body weight (range 1.2-17.1%), and four patients required
      nutritional assistance with nasogastric feeding tube. CONCLUSION: The results of
      this study show that this biphasic acceleration regimen is feasible with
      acceptable acute toxicity.

PMID- 8985038
TI  - Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for
      children with newly diagnosed medulloblastoma and other primitive neuroectodermal
      tumors.
AB  - PURPOSE: This single-institution Phase III study conducted from 1989 to 1995
      evaluates the feasibility of a multimodality protocol combining hyperfractionated
      craniospinal radiotherapy (HFRT) followed by adjuvant chemotherapy in 23 patients
      with newly diagnosed primitive neuroectodermal tumors (PNET) arising in the
      central nervous system. METHODS AND MATERIALS: All 23 patients had a
      histologically confirmed PNET and were over 3 years of age at diagnosis. The
      eligibility criteria for PNET patients with cerebellar primaries
      (medulloblastoma) included either a high T stage (T3b or 4) or high M stage (M1
      3). All patients with noncerebellar primaries were eligible regardless of T or M
      stage. The median age of the 23 patients was 9 years (mean 3-25); 11 were female.
      The primary tumor arose in the cerebellum in 19. Of these medulloblastoma
      patients, 15 had high T stages (T3b or T4) with large locally invasive tumors and
      no evidence of metastases (M0), constituting Group 1. Thirteen (86%) of these
      patients had gross total resections. Four other medulloblastoma patients had both
      high T and high M stages, constituting Group 2. Group 3 consisted of four other
      patients with exocerebellar primaries (two brain, one brain stem, and one cauda
      equina), three of whom were M3. Hyperfractionated radiotherapy was administered
      within 4 weeks of surgery. Twice-daily 1-Gy fractions were administered separated
      by 4-6 h. The total dose to the primary intracranial tumor and other areas of
      measurable intracranial disease was 72 Gy. The prophylactic craniospinal axis
      dose was 36 Gy, and boosts of 44-56 Gy were administered to metastatic spinal
      deposits. Following radiotherapy, monthly courses of multiagent chemotherapy were
      administered sequentially (cyclophosphamide-vincristine followed by cisplatin
      etoposide followed by carboplatin-vincristine) for a total of 9 months. RESULTS:
      All patients completed radiotherapy as planned. Only three patients lost >10% of
      their body weight. One patient had clinically apparent radiation-induced
      esophagitis. The mean white blood count (WBC) nadir was 2.5/dl, and hematologic
      recovery occurred in all within 4 weeks of completing HFRT without the need of
      granulocyte-colony-stimulating factor. Two patients refused adjuvant
      chemotherapy, 3 patients experienced tumor progression during chemotherapy, and 2
      of 18 remaining patients could not tolerate the full 9 months owing to
      hematologic toxicity. Of the 15 patients (93%) in Group 1, 14 remain in
      continuous remission for a median of 78 months, and none have died. Two of four
      patients in Group 2 are in continuous remission at 67 and 35 months, and two died
      at 18 and 30 months. One of the two patients in Group 2 who died refused adjuvant
      chemotherapy and developed tumor progression in the bone marrow. None of the
      three patients in Group 3 with evaluable disease (M3) had a complete response to
      therapy, and eventually all four died of progressive or recurrent disease.
      CONCLUSION: This multimodality protocol is feasible in the short term, and long
      term monitoring of neurocognitive and neuroendocrine effects are in progress.
      Excellent long-term disease control has been achieved for medulloblastoma
      patients with high T stages who were M0 at diagnosis (Group 1), the majority of
      whom had gross total resections. This group has a progression-free survival of
      95% after a median period of follow-up of 6.5 years. Alternative treatment
      strategies must be developed for patients with high M stages, as five of seven
      patients died of progressive or recurrent disease.

PMID- 8985039
TI  - Survival improvement in anaplastic astrocytoma, combining external radiation with
      halogenated pyrimidines: final report of RTOG 86-12, Phase I-II study.
AB  - PURPOSE: This study evaluated the toxicity and tumor efficacy of the
      halopyrimidine IUdR as a chemical modifier of radiation response in patients with
      malignant glioma. The preliminary results published in 1993 demonstrated no real
      advantage in the group of patients with glioblastoma. However, a benefit appeared
      to be evolving in the group of patients with Anaplastic Astrocytoma (AA). We are
      now presenting the results on the long-term follow-up of patients with AA.
      METHODS AND MATERIALS: Between August 1987 and October 1991, 79 patients were
      entered in a prospective study with newly diagnosed malignant glioma. Twenty-one
      of 79 were AA. The study was designed to have a fixed dose of radiation
      consisting of 60.16 Gy in 32 fractions in 6.5 weeks but varying the dose schedule
      of IUdR, delivered in a continuous intravenous infusion of long (96 h) or short
      (48 and 24 h) duration, every week for the 6.5 weeks of radiation treatment.
      RESULTS: The last AA patient was entered in March 1991. Ninety-five percent of
      the AA patients were under 59 years of age and 86% had a Karnofsky score 80.
      Thirty-eight percent had a tumor diameter of less than 5 cm and 52% had a tumor
      diameter between 5-10 cm. Seventy-six percent had partial or total tumor
      resection. The toxicity of this treatment was acceptable and has already been
      published elsewhere. At the time of this report, 14 out of 21 patients with AA
      are dead. The median survival, calculated from the Kaplan-Meier, is 3.2 years.
      Thirty-three percent of the patients have survived 5 years. These results compare
      favorably with the best results reported in the literature with postoperative
      external radiation plus chemotherapy, median survival time (MST) of 3 years, and
      previous Radiation Therapy Oncology Group (RTOG) experience with radiation alone,
      MST of 2 years. CONCLUSIONS: Our findings in patients with AA corroborate the
      improved therapeutic results published recently when combining external radiation
      with "long" infusion of i.v. BUdR and indicate the need to proceed with
      randomized Phase III studies utilizing halogenated pyrimidines and radiation. One
      such study has already been activated, RTOG # 94-04.

PMID- 8985040
TI  - A phase I and II clinical trial of a newly developed ultrasound hyperthermia
      system with an improved planar transducer.
AB  - PURPOSE: The clinical usefulness of a newly developed ultrasound hyperthermia
      system was evaluated. METHODS AND MATERIALS: The hyperthermia system uses a
      modified planer transducer operated at frequencies of 0.5, 1.0, and 1.5 MHz. The
      transducer has a nonvibrating part at the center to reduce the central hot spot.
      Frequency sweeping technique is also used to eliminate the annular hot spot
      around the center. Thirty-eight tumors in 29 patients were examined in this
      study. In 35 tumors, hyperthermia was given in conjunction with irradiation
      and/or chemotherapy, and in the remaining 3 tumors, hyperthermia alone was given.
      In all, a total of 153 hyperthermia sessions were performed. RESULTS: The number
      of hyperthermia sessions per tumor ranged from 1 to 7 (mean, 4.0 +/- 1.3). The
      number of intratumor thermometry points per session ranged from 1 to 8 (mean, 4.3
      +/- 1.5). The average intratumor temperature for tumors with a maximum depth of
      <3 cm, 3-6 cm, and >6 cm was 42.1 +/- 1.2, 41.7 +/- 1.4, and 39.9 +/- 2.0 degrees
      C, respectively. The percentage of monitored intratumor points with temperature
      exceeding 42 degrees C was 56 +/- 31%, 43 +/- 34%, and 21 +/- 24%, respectively.
      Of the 30 evaluable tumors treated with combined irradiation, 12 showed complete
      response, 14 partial response, and 4 no change. Observed complications included
      pain at the treatment site in 13 of the 153 treatment sessions and vesicle
      formation in 3 of the 38 treatment sites. No serious complication was seen.
      CONCLUSIONS: These results indicate that the newly developed ultrasound
      hyperthermia system is clinically useful for the treatment of localized
      superficial and subsurface tumors with a maximum tumor depth of no more than 6
      cm.

PMID- 8985041
TI  - Thermosensitive liposomes: extravasation and release of contents in tumor
      microvascular networks.
AB  - PURPOSE: The purpose of this study was to determine whether hyperthermic exposure
      would accelerate drug release from thermosensitive sterically stabilized
      liposomes and enhance their extravasation in tumor tissues. MATERIALS AND
      METHODS: In vivo fluorescence video microscopy was used to measure the
      extravasation of liposomes, as well as release of their contents, in a rat skin
      flap window chamber containing a vascularized mammary adenocarcinoma under
      defined thermal conditions (34 degrees, 42 degrees, and 45 degrees C). Images of
      tissue areas containing multiple blood vessels were recorded via a SIT camera
      immediately before, and for up to 2 h after i.v. injection of two liposome
      populations with identical lipid composition: one liposome preparation was
      surface labeled with Rhodamine-PE (Rh-PE) and the other contained either
      Doxorubicin (Dox) or calcein at self-quenching concentrations. The light
      intensity of the entire tissue area was measured at 34 degrees C (the
      physiological temperature of the skin) for 1 h, and at 42 degrees or 45 degrees C
      for a second hour. These measurements were then used to calculate the fluorescent
      light intensity arising from each tracer (liposome surface label and the released
      contents) inside the vessel and in the interstitial region. RESULTS: The
      calculated intensity of Rh-PE for the thermosensitive liposomes in the
      interstitial space (which represents the amount of extravasated liposomes) was
      low during the first hour, while temperature was maintained at 34 degrees C and
      increased to 47 times its level before heating, when the tumor was heated at 42
      degrees or 45 degrees C for 1 h. The calculated intensity of the liposome
      contents (Dox) in the interstitial space was negligible at 34 degrees C, and
      increased by 38- and 76-fold, when the tumor was heated at 42 degrees and 45
      degrees C for 1 h, respectively. Similar values were obtained when calcein was
      encapsulated in liposomes instead of Dox. A similar increase in liposome
      extravasation was seen with nonthermosensitive liposomes, but negligible release
      of Dox occurred when the window chamber was heated to 45 degrees C for 1 h.
      Extravasation of liposomes continued after heating was stopped, but content
      release stopped after removal of heat. Release of Dox from extravasated liposomes
      was also seen if heating was applied 24 h after liposome administration, but no
      further enhancement of liposome extravasation occurred in this case. CONCLUSIONS:
      Our data suggest that hyperthermia can be used to selectively enhance both the
      delivery and the rate of release of drugs from thermosensitive liposomes to
      targeted tissues.

PMID- 8985042
TI  - An ultrasound system for simultaneous ultrasound hyperthermia and photon beam
      irradiation.
AB  - PURPOSE: An existing ultrasound system has been adapted for simultaneous use with
      external photon beam irradiation. The system is being used to investigate the
      potential for increased biological benefit of simultaneously combined
      hyperthermia and external beam irradiation with currently achievable temperature
      distributions. METHODS AND MATERIALS: An existing clinical ultrasound system has
      been modified for simultaneous operation with a 60Co teletherapy machine. The
      generator, thermometry system, computer, and applicators are located inside the
      treatment room, while the monitor and system control are located at the control
      console. Two approaches have been used clinically to combine the two modalities.
      In the first approach, an en-face setup is used in which the ultrasound beam and
      the photon beam travel through the same window of entry to the tumor. This is
      acheived by a reflecting system designed to deflect the ultrasound to the tumor
      while positioning the ultrasound transducer outside the radiation beam. The
      reflecting system consists of water and water-equivalent materials except for a 1
      mm sheet of polished brass that is used as the reflector. The relative pressure
      fields were measured in water at the same distance from the ultrasound source
      using a scanning hydrophone with and without the reflector at the two operating
      frequencies of the device (1.0 and 3.4 MHz) for two applicators. Radiation
      dosimetry measurements were performed to determine the relationship between 60Co
      irradiation through the reflector and absorbed dose. In the second approach the
      ultrasound and the radiation beam travel into the tumor from different windows of
      entry such that the radiation beam passes through no portion of the water bolus
      prior to entering the patient. We have termed this approach the orthogonal
      approach. For both approaches, the radiation fraction is given in the middle of
      an uninterrupted 60-min hyperthermia treatment. RESULTS: The system modifications
      did not impair the ability to effectively deliver ultrasound hyperthermia or 60Co
      teletherapy. With the en-face approach the ultrasonic patterns generated with and
      without the reflector demonstrated that the ultrasound system maintained both a
      uniform and controllable heating pattern. The 60Co beam had no effect on the
      performance of the thermocouple thermometers. The radiation beam is attenuated
      nearly uniformly by the reflector system. To date, 10 patients have been treated
      with the en-face approach and 12 have been treated with the orthogonal approach
      (90 treatments). CONCLUSIONS: The clinical implementation of ultrasound
      hyperthermia simultaneous with 60Co irradiation is technically and clinically
      feasible without any complications or hazards to the patient. The implementation
      of a reflecting device allows en-face delivery of both the ultrasound and 60Co
      irradiation. Temperatures obtained during simultaneous treatments are comparable
      to those historically obtained during sequential treatments with the same
      commercial ultrasound device.

PMID- 8985043
TI  - Phase III trial of high and low dose rate interstitial radiotherapy for early
      oral tongue cancer.
AB  - PURPOSE: Oral tongue carcinomas are highly curable with radiotherapy. In the
      past, patients with tongue carcinoma have usually been treated with low dose rate
      (LDR) interstitial radiation. This Phase III study was designed to compare the
      treatment results obtained with LDR with those obtained with high dose rate (HDR)
      interstitial radiotherapy for tongue carcinoma. METHODS AND MATERIALS: The
      criteria for patient selection for the Phase III study were: (a) presence of a
      T1T2N0 tumor that could be treated with single-plane implantation, (b)
      localization of tumor at the lateral tongue border, (c) tumor thickness of 10 mm
      or less, (d) performance status between O and 3, and (e) absence of any severe
      concurrent disease. From April 1992 through December 1993, 15 patients in the LDR
      group (70 Gy/4 to 9 days) and 14 patients in the HDR group (60 Gy/10 fractions/6
      days) were accrued. The time interval between two fractions of the HDR
      brachytherapy was more than 6 h. RESULTS: Local recurrence occurred in two
      patients treated with LDR brachytherapy but in none of the patients treated with
      HDR. One- and 2-year local control rates for patients in the LDR group were both
      86%, compared with 100% in the HDR group (p = 0.157). There were four patients
      with nodal metastasis in the LDR group and three in the HDR group. Local
      recurrence occurred in two of the four patients with nodal metastases in the LDR
      group. One- and 2-year nodal control rates for patients in the LDR group are were
      85%, compared with 79% in the HDR group. CONCLUSION: HDR fractionated
      interstitial brachytherapy can be an alternative to traditional LDR brachytherapy
      for early tongue cancer and eliminate the radiation exposure for medical staffs.

PMID- 8985044
TI  - The use of radiologically placed gastrostomy tubes in head and neck cancer
      patients receiving radiotherapy.
AB  - PURPOSE: Patients undergoing radiotherapy to the head and neck area frequently
      experience radiation reactions that can markedly restrict oral intake, require
      hospitalization, and occasionally cause treatment interruptions. The Vancouver
      Cancer Center (VCC) has recently employed radiologically placed gastrostomy tubes
      (G-tubes) in the management of this problem. A review of the patients on whom
      this procedure had been performed is the subject of this review. METHODS AND
      MATERIALS: Thirty-four patients had gastrostomy tubes inserted under radiologic
      guidance. This group is compared to a control group matched for age, sex,
      irradiated volume, and radiation dose, who did not have gastrostomy tubes.
      Patients with gastrostomy tubes were divided into two categories: (a) patients
      who had tubes inserted in anticipation of severe reactions, and (b) patients who
      developed severe radiation reactions necessitating nutritional support. RESULTS:
      The gastrostomy group consisted of 65% males with an average age of 59 years and
      stage range of II (12%), III (24%), and IV (65%). In both the elective group and
      the nonelective group, patients maintained their weight at 95 to 97% of the
      pretreatment weight, at follow-up of 6 weeks and 3 months. This compared with an
      average weight loss in the control group of 9% at 6 weeks and 12% at 3 months.
      The length of hospitalization was a mean of 4.9 days in the elective group and 19
      days in the nonelective group. Complication were low compared to those documented
      in the literature, but included two tube migrations, two aspirations, and one
      gastrointestinal bleed. CONCLUSIONS: We believe that gastrostomy tubes contribute
      significantly to the management of patients with head and neck cancer,
      particularly in maintanence of nutrition, and they may decrease the need for
      hospitalization.

PMID- 8985045
TI  - Radiation therapy in early carcinoma of the glottic larynx T1N0M0.
AB  - PURPOSE: The Purpose of this report is to present the local control rate and
      survival of patients treated by radiation therapy for T1N0M0 squamous cell
      carcinoma of the glottic larynx. METHODS AND MATERIALS: A total of 41 patients
      with squamous cell carcinoma of the glottis were treated at the Veterans
      Administration Medical Center Minneapolis, MN, between 1976 and 1990. Of the 41
      patients, 40 are available for retrospective analysis with a minimum of a 2-year
      follow-up and a median follow-up of 5.8 years. Treatment was given to all the
      patients by a 4 MeV linear accelerator. The vast majority of the patients were
      treated with bilateral laryngeal opposed wedged 6 x 6 cm fields with a dose of
      1.75 Gy per fraction to a total of 70 Gy in 40 fractions over 56 elapsed
      treatment days. RESULTS: The data indicated local control and survival of 92.3 %
      at 2 years and 91.8 % at 3 years, post irradiation, with ultimate disease-free
      survival after surgical salvage of 97.4 % and 97.2 % at 2 years and 3 years,
      respectively. These local control and survival rates are comparable to those
      published in the literature when a higher fractional dose was given. No patients
      developed notable complications with our technique. CONCLUSIONS: A dose of 1.75
      Gy to 1.8 Gy per fraction to a total of 70 Gy in 56 elapsed treatment days is
      well tolerated and yields ultimate disease free-survival of 97.2% at 3 years.
      This time-dose fractionation could be used safely for treating patients who
      demonstrate low tolerance to irradiation with a risk of laryngitis, laryngeal
      edema, or difficulty of swallowing, with a higher fractional dose.

PMID- 8985046
TI  - Results of a trial with topotecan dose escalation and concurrent thoracic
      radiation therapy for locally advanced, inoperable nonsmall cell lung cancer.
AB  - PURPOSE: To conduct a dose escalation clinical study with topotecan and
      concurrent standard dose thoracic irradiation to assess its feasibility and
      toxicity in the treatment of patients with locally advanced, inoperable nonsmall
      cell lung cancer (NSCLCA). METHODS AND MATERIALS: Between April 1993 and August
      1994, 12 patients with inoperable, loco-regionally advanced NSCLCA were entered
      in a prospective dose escalation trial and assigned to receive concurrent
      thoracic radiotherapy and topotecan. Patients received thoracic irradiation to a
      total tumor dose of 60 Gy in 30 fractions. Initial fields were to encompass the
      gross disease plus the mediastinum. Topotecan was delivered by bolus injection
      days 1 through 5, and days 22 through 26, beginning on the same day as the
      radiation therapy. The initial dose level was 0.5 mg/m2. Two additional dose
      levels of 0.75 mg/m2 and 1.0 mg/m2 were tested. RESULTS: Six patients were
      accessioned to the 0.5 mg/m2 dose level, three patients to the 0.75 mg/m2 dose
      level, and three patients to the 1.0 mg/m2 dose level. At the 0.5 mg/m2 dose
      level, zero of six patients had > or = Grade 4 hematologic toxicity. One of the
      six had Grade 3 esophagitis. At the 0.75 mg/m2 dose level, two of three patients
      had > or = Grade 3 nonhematologic toxicity including anorexia, fatigue, nausea,
      vomiting, and weakness; zero patients experienced > or = Grade 4 hematologic
      toxicity. At the 1.0 mg/m2 dose level one of three patients had > or = Grade 3
      esophagitis, and two of three patients experienced Grade 4 neutropenia. With a
      follow-up of 12 to 24 months, two patients are alive and free of disease, three
      patients are alive with disease (two with distant metastasis, one with local
      disease and distant metastasis), and the remaining seven patients are dead of
      disease. CONCLUSIONS: The combination of topotecan and thoracic radiotherapy for
      nonsmall lung cancer, in the manner given by this protocol, could be safely given
      at a dose level of only 0.5 mg/m2 days 1 to 5 and 22 to 26 with 60 Gy of external
      beam radiotherapy. Higher doses of topotecan were associated with high
      hematologic and gastrointestinal toxicity. Distant metastasis was the primary
      pattern of failure.

PMID- 8985047
TI  - Acute radiation thyroiditis.
AB  - PURPOSE: Radiation-induced thyroid dysfunction is considered a late effect. We
      prospectively assessed acute reactions of the thyroid to external neck
      irradiation. METHODS AND MATERIALS: This study included 22 patients in whom the
      thyroid was incidentally exposed to therapeutic doses of radiation. Thyroid
      function tests included measurements of serum thyroid stimulating hormone (TSH),
      free and total triiodothyronine (T3) and thyroxine (T4), thyroglobulin, and
      antithyroid antibodies. These tests were performed before radiotherapy (baseline
      values), after approximately 40 Gy had been administrated, 2 weeks after the end
      of radiotherapy, and 3 and 6 months after the beginning of radiotherapy. RESULTS:
      Mean serum levels of TSH were 1.53, 0.55, 0.78, 2.14, and 7.57 microU/ml before
      radiotherapy, after 40 Gy irradiation, 2 weeks after the end of radiotherapy, and
      3 and 6 months after radiotherapy, respectively. Thus, levels of TSH exhibited
      two phases: a significant decrease during radiotherapy (thyrotoxic phase) and an
      increase after radiotherapy (hypothyroid phase) (baseline vs. 40 Gy: p < 0.0001,
      baseline vs. 6 months: p = 0.003). Increases of thyroid hormones were subtle
      during radiotherapy. CONCLUSIONS: We believe that radiation promotes release of
      excessive amounts of thyroid hormones during radiotherapy owing to suppression of
      TSH secretion. In addition to the late damage (hypothyroidism), thyrotoxicosis
      occurs when the thyroid gland receives a therapeutic doses of external radiation.

PMID- 8985048
TI  - Evaluation of dose calculation algorithm of the peacock system for multileaf
      intensity modulation collimator.
AB  - PURPOSE: To evaluate the dose calculation algorithm used in the inverse treatment
      planning computer system for the intensity modulation multileaf collimator.
      METHODS AND MATERIALS: The inverse treatment-planning computer system calculates
      the intensities of multiple pencil beams to achieve an optimal distribution and
      modulates the beam intensity through the special multileaf collimator. The
      system's dose calculation algorithm made the two basic assumptions: (a) The
      tissue-maximum ratios (TMRs) of a single pencil beam have the same values as TMRs
      for raylines through each pencil beam that are determined from percentage depth
      dose isodose curves along the long axis of the 2 x 20 cm2 field with all leaves
      open; and (b) the relative output factors (ROF) of each pencil beam also have the
      same values as the rayline TMR at d(max) of the 2 x 20 cm2 field. To verify these
      two assumptions, a special multileaf collimator was installed to our linear
      accelerator which produces 4 MV x-rays. The TMRs and ROFs for the single leaves 1
      through 10 were measured using an ion chamber and TLD dosimeter in either a water
      or a polystyrene phantom. The values of rayline TMRs were calculated from the
      measured crossplane isodose curves of the 2 x 20 cm2 field. Comparisons were made
      between these two sets of data. RESULTS: Based on our measurements, we found that
      the ROFs of a pencil beam obtained from the rayline TMRs at d(max) are as much as
      7.6% greater than that of single pencil beams. The ROF of the 1 x 1 cm2 pencil
      beam is 4 and 6.5% less than that of a cluster of four neighboring pencil beams
      forming a 2 x 2 cm2, and a 2 x 20 cm2 field respectively. However, the rayline
      TMRs are generally larger than the TMRs of a single pencil beam. At a depth of 8
      cm, the average depth in the middle of intracranial space, the rayline TMRs of
      the pencil beams of leaves 1 and 10 are 5.4 and 9% higher than a single pencil
      beam TMR at the same depth, respectively. Also interesting is to note that the
      TMRs of each of the single pencil beams were found to be equal. CONCLUSIONS: In
      our article, evaluations and comparisons of TMRs and ROFs were made for two
      extreme conditions. The measured values of TMRs and ROFs of a single beam have
      been shown to be significantly different from those used in the calculations.
      Because both the TMR and ROF are influenced by the scattering radiation in the
      same direction, the deviations for these two factors would be expected to be
      magnified. Thus, for the two extreme situations we have investigated, dose
      deviations would be on the order of 15%. In real patient treatment; of course,
      these deviations may be somewhat less, but still significant. Our results,
      however, show that further investigations are warranted.

PMID- 8985049
TI  - Implementation, uptime, and safety of a pulsed dose rate afterloading machine.
AB  - PURPOSE: To review the routine use of pulsed dose rate brachytherapy (PDR) for
      replacement of low dose rate manual afterloading using classical dose rates and
      hourly pulses. Uptime (actual treatement time vs. planned time) and safety (dose
      to personnel, machine safety) of 110 implants in 101 patients were evaluated
      during the period from August 10, 1993 to December 27, 1994. METHODS AND
      MATERIALS: This study includes 80 implants in gynecological tumors; 12 for
      sarcoma and 6 each for bronchus, gastrointestinal, and head and neck tumors.
      Thirty-seven of these implants were in 14 patients with a recurrence in
      previously irradiated areas. In 15 patients brachytherapy was the only treatment.
      All pulses were given hourly, and the median dose rate at specification points
      was 0.6 Gy (0.4 to 3 Gy). The total number of pulses per treatment varied from 3
      to 120. RESULTS: After an initial period of machine-related problems, all
      treatments were supported well in all but one patient and could generally be
      given within 5 min of the planned time although the room was entered at a mean
      interval of 79 min. Whenever a problem that could interfere with proper machine
      function is detected, a message (status code) is generated. A median of one
      status code (range: 0 to 24) occurred during a single implant. Status codes were
      caused by an open door when a pulse had to be given (44%) or related to
      difficulty of movement of the check cable/source through plastic tubes (34%); the
      remaining status codes were due to a variety of causes. The dose received by the
      personnel decreased almost ninefold as compared to the period when permanent
      implants were used. CONCLUSIONS: We find PDR at hourly pulses to be feasible,
      safe, and both staff- and patient-friendly. For evaluation of the clinical
      results longer follow-up is needed.

PMID- 8985050
TI  - The Sievert integral revisited: evaluation and extension to 125I, 169Yb, and
      192Ir brachytherapy sources.
AB  - PURPOSE: The goal of this study is to assess the accuracy of the Sievert integral
      dose calculation model for medium and low-energy brachytherapy sources (photon
      energy: 25-500 keV). A simple modification of the basic model, the isotropic
      scattering correction, is proposed that significantly improves its accuracy.
      METHODS AND MATERIALS: Both the classical model and revised Sievert algorithms
      were tested against 2D dose distributions derived from Monte Carlo photon
      transport (MCPT) calculations for the following sources: a 169Yb interstitial
      source, pulsed and high dose rate 192Ir sources and the model 6702 125I source.
      The Sievert model was implemented as a 3D numerical integral over the
      radioactivity distribution and included photon attenuation and scattering by the
      surrounding medium. The Sievert filtration coefficients were approximated by
      linear energy absorption coefficients, parameters of best fit, and curve fits to
      simulated open-air transmission measurements. The revised model consists of using
      the Sievert integral only to calculate the primary dose distribution using
      contact absorber filtration coefficients. The dose component due to photon
      scattering in the medium is assumed to be isotropically distributed and is
      modeled by point-source scatter-to-primary dose ratios. RESULTS: The classical
      Sievert integral produces maximum and RMS average dose-calculation errors ranging
      from -53 to -20% and 3 to 19%, respectively. In contrast, the revised model
      reproduces the MCPT dose distribution with maximum and RMS mean errors ranging
      from 5 to 13% and 1 to 6%, respectively. CONCLUSIONS: The classical Sievert model
      fails to accurately describe brachytherapy dose distributions around heavily
      filtered sources emitting photons with average energies of 28 to 400 keV. The
      revised Sievert model accurately models single-source dose distributions for a
      wide range of sources, using well-defined filtration coefficients and scatter
      ratios that can be measured or calculated without knowledge of the final dose
      distribution. The model is potentially useful as a single-source dose-array
      generator for clinical treatment planning in the low energy domain.

PMID- 8985051
TI  - Clinical value of proton magnetic resonance spectroscopy for differentiating
      recurrent or residual brain tumor from delayed cerebral necrosis.
AB  - PURPOSE: Delayed cerebral necrosis (DN) is a significant risk for brain tumor
      patients treated with high-dose irradiation. Although differentiating DN from
      tumor progression is an important clinical question, the distinction cannot be
      made reliably by conventional imaging techniques. We undertook a pilot study to
      assess the ability of proton magnetic resonance spectroscopy (1H MRS) to
      differentiate prospectively between DN or recurrent/residual tumor in a series of
      children treated for primary brain tumors with high-dose irradiation. METHODS AND
      MATERIALS: Twelve children (ages 3-16 years), who had clinical and MR imaging
      (MRI) changes that suggested a diagnosis of either DN or progressive/recurrent
      brain tumor, underwent localized 1H MRS prior to planned biopsy, resection, or
      other confirmatory histological procedure. Prospective 1H MRS interpretations
      were based on comparison of spectral peak patterns and quantitative peak area
      values from normalized spectra: a marked depression of the intracellular
      metabolite peaks from choline, creatine, and N-acetyl compounds was hypothesized
      to indicate DN, and median-to-high choline with easily visible creatine
      metabolite peaks was labeled progressive/recurrent tumor. Subsequent histological
      studies identified the brain lesion as DN or recurrent/residual tumor. RESULTS:
      The patient series included five cases of DN and seven recurrent/residual tumor
      cases, based on histology. The MRS criteria prospectively identified five out of
      seven patients with active tumor, and four out of five patients with
      histologically proven DN correctly. Discriminant analysis suggested that the
      primary diagnostic information for differentiating DN from tumor lay in the
      normalized MRS peak areas for choline and creatine compounds. CONCLUSIONS:
      Magnetic resonance spectroscopy shows promising sensitivity and selectivity for
      differentiating DN from recurrent/progressive brain tumor. A novel diagnostic
      index based on peak areas for choline and creatine compounds may provide a simple
      discriminant for differentiating DN from recurrent or residual primary brain
      tumors.

PMID- 8985052
TI  - History and development of radiation oncology in Japan.

PMID- 8985053
TI  - History and heritage: development of radiation oncology in China.

PMID- 8985054
TI  - The status of radiation therapy in Korea.

PMID- 8985055
TI  - Radiation oncology: an emergence as a discipline in Thailand.

PMID- 8985056
TI  - Radiosurgery for glioma patients: hope or hype?

PMID- 8985057
TI  - Comment on "survival improvement in anaplastic astrocytoma, combining external
      radiation with halogenated pyrimidines: final report of RTOG 86-12, Phase I-II
      Study".

PMID- 8985058
TI  - MRI: an important factor for decreasing the morbidities of treating vestibular
      schwannoma with radiosurgery.

PMID- 8985059
TI  - Reproducibility of infusional brachytherapy.

PMID- 8985060
TI  - Effects of electrochemotherapy on cutaneous metastases of human malignant
      melanoma.

PMID- 8985061
TI  - Regarding Martenson et al., IJROBP 35:299-303; 1996.

PMID- 8985062
TI  - The role of ultrasonography and inferior vena cava filter placement in high-risk
      trauma patients.
AB  - Undetected lower-extremity deep-vein thrombosis (LEDVT) in the trauma patient can
      lead to significant morbidity and mortality. The purpose of this study was to: 1)
      evaluate the role of ultrasonography in the early detection of LEDVT in high-risk
      trauma patients; 2) identify prognostic indicators that predict LEDVT; and 3)
      evaluate the efficacy of selected inferior vena cava (IVC) filter placement in
      the prevention of pulmonary emboli. From October 1993 through December 1994, all
      adult multiple-trauma patients admitted to the Trauma Service who required
      prolonged bed rest (>3 days) or sustained a lower-extremity, pelvic, or spinal
      fracture with paralysis were prospectively studied with serial physical
      examinations and lower-extremity venous ultrasounds within 72 hours of admission
      and then weekly until discharge. Two hundred twenty-eight patients were entered
      into the study. Thirty-nine patients (17%) developed ultrasound evidence of
      LEDVT; of these, only seven (18%) were evident on physical examination. This
      allowed 32 patients (82%) with unsuspected LEDVT to receive earlier definitive
      therapy. Multivariate logistic regression analysis of LEDVT with various
      predictors found age, hospital length of stay, and lower-extremity trauma to be
      significant predictors of LEDVT (P < 0.05). Twenty-nine patients (74%) had
      immediate IVC filter placement upon ultrasound identification of proximal LEDVT.
      None of these patients developed pulmonary emboli. Ten patients (26%) with a
      LEDVT were treated with systemic anticoagulation alone. One of these patients
      sustained a fatal pulmonary embolus. In a historic control group of 234 high-risk
      trauma patients admitted in the 14 months prior to implementing screening
      ultrasounds, six patients sustained pulmonary emboli (P < 0.05). Screening
      ultrasounds combined with selective placement of IVC filters play an important
      role in reducing the morbidity and mortality associated with LEDVT in high-risk
      trauma patients.

PMID- 8985063
TI  - Results of perineal procedures for the treatment of rectal prolapse.
AB  - The optimal surgical procedure for the management of rectal prolapse is still
      under debate. Therefore, the aim of this study was to evaluate the short-term
      outcome of perineal procedures in patients with rectal prolapse. Between April
      1989 and April 1995, all consecutive patients at the Cleveland Clinic Florida who
      underwent Delorme's procedure or perineal rectosigmoidectomy with or without
      levatoroplasty for full-thickness rectal prolapse were evaluated. Clinical and
      physiological assessments were performed before and after surgery. A standard
      continence scoring system, based on the frequency and type of incontinence (0 =
      full continence, 20 = complete incontinence) was used to assess the results of
      each procedure. Additionally, morbidity and mortality, and clinical and
      functional outcomes were evaluated. Sixty-one patients underwent perineal
      procedures for rectal prolapse; 16 patients died from comorbid conditions after
      undergoing postoperative physiologic assessment. These 55 females and 6 males,
      with a mean age of 75 (range, 48-101) years were studied. Patients were followed
      up for 27.2 (6-72) months, and mean prolapse duration was 4.2 (0.2-30) years.
      Although mean preoperative incontinence score was 15.9 (8-20), it was 6.3 (range,
      0-12) in postoperative course. Mean resection length of rectosigmoid was 23.3 (3
      71) cm, and in these patients, two (3.3%) coloanal anastomotic leaks and four
      (6.5%) anastomotic strictures were observed. There was one postoperative death.
      There were statistically significant differences among the groups relative to
      short-term recurrence rates, postoperative incontinence scores, mean resection
      length, coloanal anastomotic stricture, and leak (P< 0.001). However, pre- and
      postoperative anal manometry did not reveal statistically significant changes (P
      > 0.05) in each group or among the groups. Perineal procedures were found to be
      safe and effective in eradicating rectal prolapse and improving fecal
      incontinence in the elderly.

PMID- 8985064
TI  - Comparison of CO2 laser, electrocautery, and scalpel incisions on acute-phase
      reactants in rat skin.
AB  - Lasers and electrocautery devices have been applied as an alternative to the
      scalpel because of better hemostasis and lymphatic sealing. However, previous
      studies have demonstrated conflicting data regarding the effects of these
      modalities on the inflammatory response, the first reaction by tissue during
      wound healing. The purpose of this study is to quantitate inflammatory responses
      in rat skin following laser, electrocautery, and scalpel injury by measuring T
      kininogen (T-KGN), a major acute-phase protein in the rat and its endogenous
      substrate, cathepsin B, an important inflammatory mediator. Full-thickness wounds
      (6 cm) were created on the dorsum of Sprague Dawley rats by using a laser,
      electrocautery, or scalpel. Tissue samples were harvested at 1 hour to 21 days
      after injury. T-KGN levels were radioimmunoassayed; cathepsin B activity was
      assayed by using a synthetic substrate Z-Arg-Arg-MCA. Data were analyzed by
      analysis of variance. T-KGN levels peaked at 3 days for all modalities, although
      the laser group was statistically (P < or = 0.01) higher at 1, 3, and 7 days
      after injury. In contrast, cathepsin B activity was significantly (P < or = 0.01)
      lower at 3 days in the laser group. CO2 laser ablation incites a greater
      inflammatory response than electrocautery or scalpel injuries. High levels of T
      KGN may provide protection from proteolytic damage associated with cathepsins.

PMID- 8985065
TI  - Sternal fracture: a benign entity?
AB  - A retrospective review of the Greenville Memorial Hospital trauma registry
      revealed 70 patients admitted with sternal fractures over a 38-month period.
      Localized sternal tenderness was present in 68 (97.1%), external signs of
      contusion/ecchymosis in 33 (47.1%), and dyspnea in 10 (14.3%) patients. The
      mechanism of injury was motor vehicle crash in 64 (91.4%) patients, with 46 of
      these restrained. Isolated sternal fractures were present in 34 (48.6%) patients.
      Only one death occurred. All sternal fractures were managed with analgesia and
      rest; surgery was required only when indicated for associated injuries. No
      patient was found to have an aortic injury or clinically significant cardiac
      dysrhythmia. Conclusions in this study that differ from those in previous studies
      can possibly be attributed to an evolving mechanism of sternal injury. This
      retrospective review shows no association between sternal fracture and clinically
      significant cardiac injury or injury to the thoracic aorta.

PMID- 8985066
TI  - Nitric oxide synthase inhibition negates septic-induced alterations in
      cytoplasmic calcium homeostasis and membrane dynamics.
AB  - This study was undertaken to evaluate the role of nitric oxide (NO) in the sepsis
      induced disruption of intracellular calcium homeostasis and membrane dynamics.
      Anticoagulated whole blood was obtained from 10 healthy volunteers. Equal
      aliquots were incubated with saline (control), 2 microg/mL Escherichia coli
      endotoxin (lipopolysaccharide), 8 microg/mL NO inhibitor, N-monomethyl arginine
      (NMA), and endotoxin plus NO inhibitor (lipopolysaccharide/NMA). Erythrocytes
      were harvested, washed, and loaded with the calcium chelator, FURA-2AM, and the
      fluorescent membrane probe TMA-DPH. Cells were evaluated for both intracellular
      calcium concentration and membrane viscosity (anisotropy) by fluorescent
      spectrophotometry. Endotoxin induced a significant increase in both intracellular
      calcium concentration and anisotropy. NMA had no intrinsic affect on either of
      these cellular characteristics. NMA was, however, effective in preventing the
      endotoxin-induced changes. These results suggest that NO may play a role in the
      disruption of intracellular calcium homeostasis and erythrocyte membrane
      deformability noted in sepsis.

PMID- 8985067
TI  - Concomitant orthopedic and vascular injuries as predictors for limb loss in blunt
      lower extremity trauma.
AB  - Lower extremity trauma with concomitant orthopedic and vascular injury is
      associated with a high degree of limb loss. Despite successful arterial repair,
      many patients will ultimately require amputations. The effect of associated
      orthopedic injuries on limb loss in patients with lower extremity arterial
      injuries is investigated. From 1989 to 1994, 52 infrainguinal arterial injuries
      were identified among 365 vascular trauma patients. Clinical determinants were
      retrospectively assessed for the ability to predict postoperative amputations.
      Femoral artery injuries were present in 23 patients, with 53 per cent the result
      of blunt trauma. The incidence of lower extremity fractures was 53 per cent (60%
      open). Seventy-nine per cent of femoral artery injuries were repaired with
      saphenous vein grafts. Popliteal artery injuries were present in 13 patients,
      with 77 per cent the result of blunt trauma. The incidence of lower extremity
      fractures and posterior knee dislocations was 85 per cent (73% open) and 38 per
      cent, respectively. Ninety-two per cent of injuries were repaired with saphenous
      vein grafts. Tibial artery injuries were present in 16 patients, with 44 per cent
      the result of blunt trauma. The incidence of lower extremity fractures was 81 per
      cent (46% open). Twenty-five per cent of tibial artery injuries were treated with
      arterial repair, and 31 per cent with arterial ligation. Fourteen above-knee
      (AKA) and two below-knee amputations were performed. Amputation rates were 26.1
      per cent (three AKAs) for femoral, 53.8 per cent (seven AKAs) for popliteal, and
      38 per cent (four AKAs, two below-knee amputations) for tibial artery injuries.
      At the popliteal and femoral locations, greater than two long-bone fractures was
      predictive of amputation. For tibial arteries, one-vessel (n = 10), two-vessel (n
      = 3), and three-vessel (n = 3) injuries were associated with 20, 33, and 100 per
      cent amputations rates, respectively. Blunt injury, pulseless extremity, need for
      arterial repair (rather than ligation or no therapy), increasing number of
      injured tibial vessels, and multiple long-bone fractures were predictors of
      amputation (P < 0.05). Distal vascular injuries combined with complex orthopedic
      fractures are more likely to result in limb loss. Two or more long-bone fractures
      is predictive of amputation at all three locations.

PMID- 8985068
TI  - Blunt hepatic injury in adolescents: age makes a difference.
AB  - This analysis of mortality from blunt hepatic injury was performed to define
      outcome in the adolescent age group in relation to that recorded for children and
      adults. Children (age 0-10 years) were selected from a multi-institutional trauma
      registry, adults (age > or = 21 years) from the registry of a Level I trauma
      center, and adolescents (age 11-20 years) from both. Groups were compared by
      injury frequency, proportion of severe hepatic injuries (code 864.03 or 864.04 in
      the International Classification of Diseases, Adapted for Use in the United
      States 9-CM), immediate laparotomy, mortality, and cause of death. Children had
      the lowest proportion of severe injury and overall mortality. Torso trauma was
      the primary cause of death in only three children. Adolescent injury patterns
      were similar to those of adults in the proportion of severe visceral disruption
      and incidence of fatal torso trauma. Immediate laparotomy was employed almost
      twice as commonly in adults as in adolescents. The 64 per cent of adolescents who
      did not undergo laparotomy had a lower mortality than those who did. Conversely,
      the 36 per cent of adults without exploration had a significantly higher
      mortality, which usually occurred before laparotomy could be initiated.
      Increasing hepatic injury severity brought increasing mortality; however, the
      cause of death differed with age. Although the incidence of severe liver injury
      did not differ between adolescents and adults, management and outcome did. These
      data indicate that individualized management based on overall patient status
      remains the best approach to care of these injuries.

PMID- 8985069
TI  - Sestamibi parathyroid scanning and preoperative localization studies for patients
      with recurrent/persistent hyperparathyroidism or significant comorbid conditions:
      development of an optimal localization strategy.
AB  - For patients with previous thyroid or parathyroid surgery and for those with
      significant comorbid conditions, noninvasive and invasive modalities exist for
      the preoperative localization of pathologic parathyroid tissue. Formal
      localization at our institution involves obtaining two studies that are
      independently positive for the same location. The studies utilized have included
      ultrasound, CT scans, MRI, technetium-99m/thallium-201 (Tc-Tl) imaging, and more
      recently, (99m)Tc-sestamibi (20-25 mCi) (MIBI) scans. These were followed by
      arteriography and/or venous sampling if necessary. From January 1992 through
      October 1995, 25 patients underwent preoperative parathyroid localization (10
      reoperation, 3 grave hypercalcemia, 2 concurrent goiter, 2 cerebral vascular
      accident, 1 bleeding disorder, and 1 malignant ventricular arrhythmia) and were
      evaluated prospectively during the changeover from Tc-Tl to MIBI scanning at our
      institution. A total of 92 studies were obtained. All 25 patients were operated
      on by a single surgeon, and in each case the parathyroid adenoma was successfully
      resected with minimal morbidity (1 permanent hypoparathyroid and 1 temporary
      recurrent laryngeal nerve injury). True positives interpreted preoperatively:
      MIBI, 14 of 19 (74%); CT scan, 13 of 19 (68%); Tc-Tl, 4 of 8 (50%), ultrasound, 9
      of 20 (45%); MRI, 8 of 14 (57%); arteriography, 3 of 7 (43%); venous sampling, 3
      of 4 (75%); and positron emission tomography, 0 of 1. There were no false
      positive MIBI scans. These results suggest that when formal parathyroid
      localization is needed in reoperative/complicated patients, 1) MIBI appears to be
      the most sensitive and specific study, and 2) the MIBI scan should be the initial
      study in any situation in which preoperative localization is needed. Ultrasound
      can be useful for patients with significant comorbidities who have not been
      previously explored. CT or MRI should then be used if further evaluation is
      needed. If the use of these noninvasive modalities does not produce positive
      gland localization, selective venous sampling should be utilized as the
      definitive procedure.

PMID- 8985070
TI  - Autotransfusion utilization in abdominal trauma.
AB  - The purpose of this review is to investigate the utility of autotransfusion in
      trauma patients in the past 3 years. A retrospective review was conducted of the
      charts for whom the Haemonetics Cell Saver autotransfusion device (Haemonetics
      Corp., Natick, MA) was utilized between January 1, 1993, and December 31, 1995.
      The estimated blood loss and quantity of blood transfused were noted for
      abdominal trauma patients. Costs of autotransfusion were then compared to
      estimated blood bank costs for this group. The Haemonetics Cell Saver
      autotransfusion device was requested for 592 cases from January 1, 1993, to
      December 31, 1995. Nonorthopedic trauma cases comprised 25 per cent of all
      autotransfusion cases. One hundred twenty-six patients had isolated abdominal
      trauma and had a mean estimated blood loss of 4864 +/- 6070 cc. The average
      volume of intraoperatively salvaged autologous blood transfused (autotransfusion)
      per patient was 1547 +/- 2359 cc, or a bank blood equivalent of 6.9 units of
      packed red blood cells. The total cost of autotransfusion in these patients was
      $63,252.00. Had bank blood been used instead of salvaged autologous blood, the
      cost would have been $114,523.00; thus, autotransfusion resulted in a savings of
      $51,271.00. The use of salvaged autologous blood comprised 45 per cent of total
      blood transfused. On a case-by-case basis, 75 per cent of cases were cost
      effective compared to blood bank costs for an equivalent transfusion. Transfusion
      of intraoperatively salvaged autologous blood (autotransfusion) is a cost
      effective, efficient way to provide blood products to operative trauma patients.

PMID- 8985071
TI  - Intraoperative duplex scanning reduces both residual stenosis and postoperative
      morbidity of carotid endarterectomy.
AB  - To evaluate the effect of intraoperative duplex scanning (IDS) on the incidence
      of perioperative and postoperative strokes as well as residual and recurrent
      stenosis, we reviewed 141 patients who underwent 152 consecutive carotid
      endarterectomies (CEAs) between July, 1990 and June, 1995. Follow-up of 129
      cases, with a mean follow-up of two years, revealed no perioperative deaths and
      three strokes for a combined perioperative stroke-death rate of 2.3 per cent. In
      50% (64 of 129) of the CEAs, intraoperative duplex scans were obtained based on
      the attending surgeon's preference. We noted that the incidence of residual
      stenosis (>50% stenosis on the first duplex after CEA) was significantly lower in
      those undergoing IDS (3/64) versus those without IDS (13/65) (P < 0.05; risk
      ratio 0.31; 95% confidence interval 0.11, 0.91). IDS resulted in a modification
      of the internal carotid reconstruction in 9 per cent (6 of 64) of the cases with
      no resulting postoperative strokes or residual/recurrent stenosis. There was no
      significant difference in the frequency of recurrent stenosis (>50% stenosis
      after a normal duplex) in the two groups (3 of 64 with vs 2 of 65 without). Of
      patients not undergoing intraoperative scanning, four underwent redo CEA for
      symptomatic residual stenosis due to a retained intimal flap in the internal
      carotid artery. There were three strokes observed within 30 days of the initial
      CEA, all of which occurred in patients who did not undergo IDS at their initial
      operation. We conclude that IDS can identify technical defects following internal
      carotid reconstruction, thereby reducing the incidence of both residual stenosis
      and postoperative morbidity in patients undergoing CEA.

PMID- 8985072
TI  - Traditional and future management of nonpalpable breast cancer.
AB  - Under the impact of mammographic screening, sizeable proportions of breast cancer
      patients today are nonpalpable with either a very small invasive breast cancer
      (T1a or T1b) or ductal carcinoma in situ. At the Deaconess Hospital in Boston
      between 1989 and 1993, 29 per cent of all invasive cancers were T1a or T1b (1 cm
      or smaller). The median maximum diameter of all invasive breast cancer in that 5
      year period was only 1.5 cm. The dramatic downward slope of the maximum size
      clearly reflects the impact of widespread mammographic screening. Within a
      decade, the median maximum diameter of all invasive breast cancer will be 1 cm.
      Thus, modifications of contemporary therapy need to be investigated by trials,
      but they can be practiced in selected patients now. While standard therapy in
      1996 includes routine radiotherapy with breast conservation, many small, low
      grade, or mammographically discovered cancers can safely, efficiently, and with
      minimum morbidity be treated by local excision only with careful follow-up;
      highly selective use of systemic and local adjuvant therapies (i.e.,
      radiotherapy) should also be practiced. Recent reports summarizing adjuvant
      radiotherapy and axillary dissection in invasive breast cancer do not recognize
      the changing presentation of invasive breast cancer under the impact of
      mammographic screening.

PMID- 8985073
TI  - Studies on the duration of antibiotic administration for surgical prophylaxis.
AB  - Patients undergoing 801 elective, clean-contaminated operations were assigned to
      one of the three following antibiotic regimens: 1) 1 g of cefazolin
      preoperatively, 2) 1 g of cefazolin preoperatively and another 1-g dose 3 hours
      later, and 3) 1 g of cefotetan preoperatively. These antibiotic regimens resulted
      in similar wound infection rates for procedures completed within 3 hours. When
      the procedure lasted more than 3 hours, the 6.1 per cent infection rate noted
      when a single dose of cefazolin was given proved significantly greater than the
      1.3 per cent infection rates associated with the use of two doses of cefazolin or
      a single dose of the longer acting antibiotic, cefotetan (P < 0.01). Another
      series of 768 patients undergoing biliary and gastrointestinal tract operations
      were assigned to one of two antibiotic regimens: 1) a preoperative dose of 1 g of
      cefazolin and another 1-g dose 3 hours later if still in the operating room; 2)
      same as (1), plus 1-g doses every 8 hours for 24 hours. The longer period of
      antibiotic administration failed to improve the wound infection rate compared to
      the use of perioperative coverage only. These studies suggest that a single dose
      of preoperative antibiotic is sufficient for surgical prophylaxis when the
      operation is completed within 3 hours. Antibiotic coverage must extend for the
      duration of longer operations. A second dose of antibiotic or a single
      preoperative dose of an extended half-life antibiotic are equally effective.
      There is no value to administering antibiotics after the operation has been
      completed.

PMID- 8985074
TI  - Cryosurgical ablation of hepatic metastases from colorectal carcinomas.
AB  - Surgical resection remains the only curative therapy for hepatic metastases from
      colon and rectal carcinoma. Many patients will be unresectable or have close
      microscopic margins. Cryoablation may improve local control and survival in those
      cases. From February 1992 to May 1995, patients with metastatic colon and rectal
      carcinoma who underwent cryoablation of surgical margins following hepatic
      resection or cryoablation of hepatic metastases were reviewed with attention to
      patient and tumor characteristics, clinical course, local control, and survival.
      Twenty-four patients (10 female, 14 male) with a mean age of 63 years (range, 34
      84 years) underwent cryosurgical ablation for hepatic metastases. Twelve were for
      central lesions and 12 for gross or microscopically positive resection margins.
      Surgery was performed with curative intent for 21 and for palliation in 3
      patients. The mean hospital stay was 8.4 days (range, 5-15 days). Complications
      included three cases of parenchymal cracking and a single bile leak. Two of 14
      patients who developed pleural effusions required treatment. Perioperative
      mortality was 8.3 per cent (2 of 24): one myocardial infarction and one
      cerebrovascular accident. Four of 21 treated for cure had hepatic recurrence, and
      six had only extrahepatic recurrence. Median time to recurrence was 9.5 months.
      With median follow-up of 19 months, mean actuarial disease-free (DFS) and overall
      survival (OS) rates are as follows. Those with central lesions (n = 12) had a
      mean OS rate of 31 months and a mean DFS rate of 23 months. Those with close
      resection margins (n = 12) had a mean OS rate of 31 months and a median DFS rate
      of 19.5 months. Total patients (n = 24) had a mean OS rate of 32.7 months and a
      mean DFS rate of 23.5 months. We conclude that cryoablation of unresectable
      hepatic metastases or close resection margins is safe and may allow for improved
      survival in selected patients with metastatic colon and rectal carcinoma.

PMID- 8985075
TI  - Biliary dyskinesia and biliary crystals: a prospective study.
AB  - The management of patients with biliary colic without gallstones has remained
      controversial in part because a mechanism for "biliary dyskinesia" has not been
      elucidated. A prospective study was done on patients presenting with biliary
      colic symptoms but without demonstrable gallstones. Thirty-six patients were
      evaluated with ultrasound and hepatobiliary/cholecystokinin scintigraphic
      scanning. Patients with gallbladder ejection fractions of less than 35 per cent
      and/or symptoms reproducible with cholecystokinin were offered cholecystectomy.
      At cholecystectomy, bile was aspirated from the gallbladder for crystal analysis.
      A random sample of 36 patients with gallstones undergoing cholecystectomy were
      analyzed as a control group. Pathologic evaluation was done; the gallbladder wall
      was examined using polarized microscopy to determine the presence of crystals
      within the gallbladder wall. The mean gallbladder ejection fraction in patients
      without stones was 24.1 per cent and in patients with stones, 34.6 per cent (P =
      0.14). 89.7 per cent of patients without stones had crystals in their gallbladder
      bile. 61.8 per cent of patients without stones and 81.3 per cent of patients with
      stones (P = 0.22) had crystals within their gallbladder walls. 94.1 per cent of
      patients without stones and 100 per cent of patients with stones (P = 0.49) had
      pathologic evidence of chronic cholecystitis. These data suggest that a spectrum
      of biliary disease exists in which bile saturation and gallbladder dysmotility
      lead to crystal growth and subsequent gallstone formation and chronic
      inflammation. Biliary pain may be generated at any point in this spectrum.

PMID- 8985076
TI  - The effects of epidural anesthesia on the neuroendocrine response to major
      surgical stress: a randomized prospective trial.
AB  - It has long been held that the acute-phase and neuroendocrine response to stress
      requires afferent neural input for its propagation. To further clarify the role
      of afferent neural impulses in this process and to determine the ability of
      epidural anesthesia to attenuate the normal perioperative stress response, 39
      patients undergoing uncomplicated abdominal aortic replacement were randomized to
      receive either general anesthesia with postoperative patient-controlled
      intravenous morphine (n = 19) or combined regional/general anesthesia with
      intraoperative epidural catheter anesthesia using Bupivacaine to the T4 dermatome
      level followed by postoperative epidural morphine (n = 20). The stress response
      was quantitated by blinded measurement of baseline and postoperative (0, 12, 24,
      48, and 72 hours) serum cortisol, epinephrine norepinephrine, total
      catecholamines, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha,
      and C-reactive protein (CRP). Total operative time (4.2 +/- 0.3 vs 4.3 +/- 0.4
      hours), 72-hour fluid requirement (7.0 +/- 0.6 vs 6.8 +/- 0.71 mL), and length of
      hospitalization (7.8 +/- 1.4 vs 8.1 +/- 1.2 days) were not different between
      groups. All patients showed a significant increase in cortisol, epinephrine,
      norepinephrine, total catecholamines, CRP, and IL-6 in the postoperative period
      (P < 0.05). IL-1beta and TNF-alpha were less predictable and undetectable in most
      patients. There was no difference in any of the stress response indices between
      those patients receiving patient-controlled or epidural catheter anesthesia. In
      fact, the only parameter that was predictive of increased activation of the
      stress response was the length of operation, irrespective of anesthetic method.
      Those patients with operative times greater than 5 hours (n = 10) developed
      significantly higher CRP, IL-1beta, IL-6, and TNF-alpha levels (P < 0.05) at 12
      and 24 hours postoperatively than those with total operative times less than 4
      hours (n = 16). The neuroendocrine response to major surgical stress is
      propagated normally despite epidural blockade and is intensified with prolonged
      operative times. The inflammatory cytokines appear to play a major role in this
      process.

PMID- 8985077
TI  - The utility of preoperative laboratory testing in general surgery patients for
      outpatient procedures.
AB  - The utility of obtaining routine preoperative laboratory (lab) screening tests
      was evaluated for a 1-year period in general surgery clinic patients undergoing
      ambulatory surgical procedures at a teaching hospital. This study sought to
      determine whether those lab tests not indicated by patient history or physical
      examination would identify abnormalities that might influence perioperative care
      of the ambulatory surgical patient or predict perioperative complications. The
      charts of 142 patients undergoing 155 procedures were reviewed. A total of 300
      tests were ordered, with 92 (30.6%) being abnormal. Of the 125 tests indicated,
      54 (43.2%) were abnormal, whereas in those lab tests not indicated, 38 (21.7%)
      were found to be abnormal. In four instances, an abnormal lab test (4 out of 300)
      result was clinically significant (1.3%), causing cancellation of the surgical
      procedure in two cases (both indicated lab tests) and diagnosis of urinary tract
      infection in two patients (both routine urinalyses). Forty-eight of the 142
      patients had no preoperative lab tests ordered (34%), with no perioperative
      complications resulting. Patient charges totaled $15,725 for all lab tests
      ordered, with $8,573 in charges attributed to those tests not indicated. If lab
      tests for all general and subspecialty surgical outpatients had been ordered as
      dictated by patient medical history and physical examination rather than by
      either routine or by arbitrary criteria, our medical facility could have
      potentially reduced patient charges by more than $400,000 in the year reviewed,
      assuming a 52.4 per cent savings as noted above, with no expected adverse
      outcomes.

PMID- 8985078
TI  - Laparoscopic cholecystectomy: applicability in the geriatric population.
AB  - Elderly patients with cholelithiasis are more likely than nonelderly patients to
      present with an acute complication of gallstone disease such as acute
      cholecystitis (AC), gallstone pancreatitis (GSP), or common bile duct stones
      (CBDS). These acute complications may make laparoscopic cholecystectomy (LC) more
      hazardous, with a potential increase in perioperative morbidity or need for open
      conversion. The applicability of LC in the geriatric population is, therefore,
      unclear. We reviewed 283 consecutive patients undergoing attempted LC. Patients
      were classified as presenting with complicated (AC, GSP, or CBDS) or
      uncomplicated gallstone disease. Elderly patients were significantly more likely
      than younger patients to present with AC (40% versus 18%), GSP (19% versus 6%),
      and CBDS (21% versus 5%) (all P < 0.05). Elderly patients with chronic,
      uncomplicated gallstone disease (n = 20) and nonelderly patients with
      uncomplicated disease (n = 159) had similar open conversion rates (5% and 7%,
      respectively). In contrast, the open conversion rate in elderly patients with
      complicated gallstone disease (n = 42) was significantly higher (50%) compared to
      nonelderly patients with complicated disease (n = 62; rate, 16%; P < 0.05).
      Perioperative morbidity and length of stay were also significantly increased in
      the elderly group, primarily due to the high percentage of elderly patients with
      complicated disease. These results suggest that elderly patients with
      uncomplicated gallstone disease appear to be excellent candidates for LC, and
      this should be considered before complicated disease develops. Conversely, early
      conversion or planned open cholecystectomy may be warranted in the elderly
      presenting with acute complications of cholelithiasis.

PMID- 8985079
TI  - Fibrin sealant reduces serous drainage and allows for earlier drain removal after
      axillary dissection: a randomized prospective trial.
AB  - Fibrin sealant (FS) has been used successfully as an effective adhesive and
      hemostatic agent in a variety of surgical procedures. At the University of
      Virginia, autologous fibrin sealant is used to reduce the potential accumulation
      of serous fluid after axillary dissection in patients undergoing modified radical
      mastectomy (MRM) for carcinoma of the breast. Unilateral MRM, including level I
      and II axillary lymph node dissection, was performed upon 21 patients
      prospectively randomized into treatment and control groups. Surgical procedures
      between both groups differed only by the application of autologous FS prior to
      axilla closure in the treatment group. Drainage was collected and measured at 24
      hour intervals following the operation. Drains were removed following the
      measurement of 40 ml or less during a 24-hour interval. Cumulative drainage for
      the first 3 postoperative days in the treatment group averaged 198 +/- 83 ml
      compared to 467 +/- 138 ml in the control group (P < 0.0003). Day of drain
      removal averaged 3.9 +/- 1.7 for the treatment group and 6.9 +/- 1.2 for the
      control group (P < 0.0001). In the treatment group, there was a reduction in
      cumulative drainage over the first 3 days of 268 ml or 57 per cent, and there was
      a reduction in the number of days before drains can be removed of 3.0 days, or 43
      per cent. We conclude that local application of FS significantly reduced the
      total drainage measured in patients undergoing MRM and enabled earlier drain
      removal.

PMID- 8985080
TI  - Laparoscopic inguinal hernia repair: is the enthusiasm justified?
AB  - One surgeon repaired 72 inguinal hernias in 61 patients by a transabdominal
      preperitoneal laparoscopic placement of prosthetic mesh. There were 58 male and 3
      female patients; the mean age was 47.9 years. Thirty-six unilateral inguinal
      hernias (either direct or indirect), 11 bilateral inguinal hernias, 12 recurrent
      inguinal hernias, and 2 unilateral pantaloon inguinal hernias were repaired.
      There were no operative mortalities. The mean follow-up was 21 months, with a
      range of 6 to 42 months. Ten hernia recurrences (13.8%) were documented 3 to 24
      months postoperatively (mean, 12 months). There were six direct hernia
      recurrences, two indirect hernia recurrences, and two recurrences of recurrent
      hernia repairs. Thirteen patients (21.3%) experienced morbidity: seromas in
      eight, a hematoma in one, an ileus in one, hematuria in one, and neuropathy in
      two. In our opinion, the significant morbidity and early recurrence rate of a
      laparoscopic inguinal hernia repair are unacceptable. Enthusiasm for laparoscopic
      technique to repair inguinal hernias is not justified if similar morbidity and
      recurrence rates are documented within the surgical community.

PMID- 8985081
TI  - General surgical clinical pathways: an introduction.
AB  - With increasing pressures to reduce the cost of health care, protocols and
      practice guidelines are being developed to streamline the practice of medicine.
      Many of these guidelines have been developed by health care workers who are not
      involved in the daily care of patients and who do not have clinical expertise in
      the specific diseases. The Southeastern Surgical Congress appointed a committee
      to develop clinical pathways for common surgical diseases. These clinical
      pathways have been developed by practicing surgeons with expertise in common
      surgical diseases and reviewed for their applicability by other surgeons with
      clinical expertise. The types of guidelines are reviewed and the need for
      guidelines are discussed. This paper presents the purpose, development, essential
      elements, and the dissemination and implementation of clinical pathways for
      common surgical diseases. It is critical that surgeons and surgical organizations
      participate in developing clinical guidelines and clinical pathways.

PMID- 8985082
TI  - Re: Spinal injury increases the risk of abdominal aortic aneurysm.

PMID- 8985083
TI  - B-CLL cells with unusual properties.
AB  - In studies concerning the interaction of B-CLL cells and Epstein-Barr virus
      (EBV), we encountered one patient whose cells had several unusual properties. In
      addition to the B-cell markers, the CLL cells expressed the exclusive T-cell
      markers CD3 and CD8 and carried a translocation t(18,22)(q21;q11), involving the
      bcl-2 and Ig lambda loci. The patient represents the 4th reported CLL case with
      this translocation. The CLL cells could be infected and immortalized by the
      indigenous and by the prototype B958 virus in vitro. The T-cell markers were not
      detectable on the established lines. In all experiments the immortalized lines
      originated from the CLL cells. Their preferential emergence over virus-infected
      normal B cells may be coupled to the high expression of the bcl-2 gene due to the
      translocation. In spite of the sensitivity of CLL cells to EBV infection in
      vitro, no EBNA-positive cells were detected in the ex vivo population. In vitro,
      we could generate cytotoxic function in T-lymphocyte cultures which acted on
      autologous EBV-infected CLL cells. Therefore we assume that if such cells emerged
      in vivo they were eliminated by the T-cell response.

PMID- 8985084
TI  - Epstein-Barr virus in lymphoproliferative diseases in the sino-nasal region:
      close association with CD56+ immunophenotype and polymorphic-reticulosis
      morphology.
AB  - Association between Epstein-Barr virus (EBV) and nasal T-cell lymphoma (NTL) has
      been demonstrated. NTL has 2 types of histologic figures: one is ordinary non
      Hodgkin's lymphoma (NHL) with monomorphous proliferation, and the other is
      polymorphic-reticulosis (PR) morphology. The presence of the EBV genome and its
      sub-types (A and B) were examined on paraffin-embedded specimens from 36 cases of
      sino-nasal lymphomas (SNL) collected from Seoul, Republic of Korea, where the
      frequency of NTL is high. Patients' ages ranged from 2 to 74 years (median 54
      years) with a male-to-female ratio of 2.5:1. Immunophenotypically, 8 cases were B
      cell type, 11 were T-cell type with CD56-, 14 were CD56+ type, and 3 were null
      cell type. Five of 11 cases with ordinary NHL of T-cell type and 9 of 14 cases
      with PR were CD56+. The EBV genome was found by polymerase chain reaction (PCR)
      and in the tumor cells by in situ hybridization (ISH) in 1 of 4 B-cell type
      (25%), 5 of 10 T-cell type (50%), 11 of 13 CD56+ type (85%), and in both of null
      cell type (100%). Of 16 cases with PR morphology, 15 (94%) were positive for the
      EBV genome. All of the 5 NTLs of ordinary NHL with CD56- were negative for EBV.
      Concerning the sub-type of EBV, 16 cases had type A, while none had type-B EBV.
      These findings suggest that NTL comprises 2 groups: EBV-positive NTLs are CD56+
      and/or histologically PR, and EBV-negative NTLs are CD56- and histologically
      ordinary NHL. The current results on Korean patients, together with earlier
      studies on Japanese and Malaysian patients, have shown the predominance of type-A
      EBV in sino-nasal lymphoma in Asia.

PMID- 8985085
TI  - Complement-regulatory proteins in ovarian malignancies.
AB  - Ovarian cancer has features that makes it well-suited for MAb adjuvant
      immunotherapy. Several of the MAbs used in clinical trials mediate cancer cell
      destruction by activation of complement (C). In this study, therefore, we
      examined the ability of ovarian-tumor cells to resist C attack. We found that the
      C regulators membrane cofactor protein (MCP, CD46) and protectin (CD59) were
      strongly expressed in the tumor cells in all 28 benign and malignant tumors
      examined. Decay-accelerating factor (DAF; CD55) was more heterogeneously
      expressed, and only 75% of the tumors exhibited a moderate amount of DAF in the
      tumor cells. In adenoma cells, CD59 and DAF were preferentially located apically,
      while in adenocarcinoma cells they were expressed also at the basolateral cell
      surface. The ovarian-carcinoma cell lines SK-OV-3, Caov-3, SW626 and PA-1
      expressed both the 58- and the 68-kDa isoforms of MCP. DAF was present as a
      glycosyl-phosphatidylinositol(GPI)-anchored 70-kDa glycoprotein. The surface
      expression level of DAF varied, and correlated with the vulnerability of the
      cells to C-mediated lysis. CD59 was expressed as a GPI-linked 19- to 25-kDa
      protein exhibiting multiple glycosylation variants. The surface expression of
      CD59 correlated with the amount of the main 1.9 + 2.1-kb CD59 mRNA transcripts.
      Neutralization of CD59 with an anti-CD59 MAb significantly enhanced C-mediated
      killing of the cell lines. Low expression of C regulators on the PA-1
      teratocarcinoma cell line was associated with high sensitivity to C lysis. Thus,
      the expression of C regulators on malignant ovarian cells may constitute a tumor
      escape mechanism, and is a critical parameter to be examined when MAb therapy is
      being considered.

PMID- 8985086
TI  - Risk factors for childhood melanoma in Queensland, Australia.
AB  - The causes of cutaneous melanoma among children under 15 years are largely
      unknown. We report the findings of an epidemiological study of childhood melanoma
      in Queensland, Australia, which has the highest incidence rates in the world. All
      61 cases of melanoma in children less than 15 years notified to the Queensland
      Cancer Registry 1987-1994 were eligible to participate in a population-based,
      case-control study. Data were collected through structured, face-to-face
      interviews with parents and skin examinations of the 52 participating cases and
      156 age- and sex-matched controls. The strongest determinants of melanoma risk
      found among Queensland children were constitutional factors, including the
      presence of more than 10 naevi greater than 5 mm in diameter (RR 9.9, 95% CI 2.5
      38.9), heavy facial freckling (RR 6.4, 95% CI 1.9-21.6), an inability to tan on
      exposure to the sun (RR 8.8, 95% CI 2.1-36.2) and a family history of melanoma
      (RR 4.2, 95% CI 1.9-9.3). These factors remained significantly associated with
      melanoma after adjusting for other risk factors. No measures of acute or chronic
      exposure to solar UV radiation were associated with childhood melanoma in our
      study. Established risk factors, including giant congenital naevi and xeroderma
      pigmentosum, were not present among any of the children in the study. Melanoma in
      childhood appears to have similar epidemiologic characteristics to the adult form
      of the disease, being associated with a cluster of phenotypic attributes
      indicating cutaneous sensitivity to the effects of sun exposure. Our findings
      support the contention that childhood melanoma occurs in susceptible individuals
      with a low threshold for pigment cell tumorigenesis. From a public-health
      perspective, children at elevated risk for melanoma can be identified on the
      basis of phenotype and family history.

PMID- 8985087
TI  - E-cadherin gene alterations are rare events in thyroid tumors.
AB  - Reduced expression of E-cadherin has been associated with loss of differentiation
      and/or increased invasiveness and metastatic ability in several types of
      neoplasms. Rare studies on thyroid tumors have shown minimal or absent expression
      in undifferentiated carcinomas and a variable degree of immunoreactivity/mRNA
      expression in follicular and papillary carcinomas. We studied
      immunohistochemically 2 follicular adenomas, 8 follicular carcinomas, 18
      papillary carcinomas and 3 poorly differentiated carcinomas to evaluate E
      cadherin expression. In 7 papillary carcinomas, lymph node metastases were also
      studied. The E-cadherin gene was analysed in 27 tumors by PCR/SSCP followed,
      whenever appropriate, by DNA sequencing. LOH at the E-cadherin locus was assessed
      in 16 tumors. Reduced and heterogeneous expression of E-cadherin was found in
      primary and metastatic papillary carcinomas, whereas follicular carcinomas showed
      moderate to strong homogeneous immunoreactivity, and poorly differentiated
      carcinomas showed no or very faint immunoreactivity. The only case harbouring a
      (missense type) mutation of the E-cadherin gene was a papillary carcinoma
      exhibiting immunoreactivity in the primary tumor as well as in metastasis. LOH
      was found in a follicular adenoma and in a poorly differentiated carcinoma
      without evidence of mutation in the remaining allele. Our results show that
      irreversible alterations (allele loss or mutation) of the E-cadherin gene are
      infrequent in thyroid tumors. The reduced and heterogeneous expression of E
      cadherin in thyroid carcinomas, particularly of the papillary histotype, appears
      to reflect transcriptional regulation or post-transcriptional modulation rather
      than structural abnormalities.

PMID- 8985088
TI  - Cancer incidence in Conakry, Guinea: first results from the Cancer Registry 1992
      1995.
AB  - We have registered 2,064 cases of cancer among the inhabitants of Conakry,
      Guinea, during 1992-1994, corresponding to age-standardized incidence rates
      (ASRs) of 83.3 per 100,000 in men and 110.5 per 100,000 in women. As elsewhere in
      West Africa, the principal cancer of men was liver cancer (ASR 32.6), with modest
      rates of stomach (ASR 6.2) and prostate (ASR 8.1) cancers. In women, cervix
      cancer was the dominant malignancy (ASR 46.0), followed by liver cancer (ASR
      12.5) and breast cancer (ASR 10.9). In contrast to contemporary East and Central
      Africa, Kaposi's sarcoma remained rare (only 4 cases). In the childhood age
      group, relatively high incidence rates were found for Hodgkin's disease,
      Burkitt's lymphoma and, especially, retinoblastoma.

PMID- 8985089
TI  - Humoral immune response against p53 protein in patients with colorectal
      carcinoma.
AB  - p53 aberrations are frequent in colorectal carcinogenesis (40-70%). Because p53
      gene mutations typically result in increased p53 protein concentration in tumor
      cells, this cellular protein might become immunogenic during tumor development.
      To test this hypothesis, serum p53 antibodies were quantitatively analyzed in 229
      patients with colorectal cancer, using an immunofluorometric procedure.
      Circulating antibodies against p53 were found in 23% (53/229) of the patients. We
      quantified antibody concentrations in all positive sera and found that they
      varied from 300 to 500,000 arbitrary units/1. Sequential analysis of positive
      sera from 3 patients showed that p53 antibody concentrations change during the
      course of the disease, reflecting progression or regression. No association was
      found between the presence of p53 antibodies and age, sex, stage, histological
      grade and patient relapse-free or overall survival. These data demonstrate that
      antibody generation against the p53 tumor-suppressor protein is a relatively
      common event in colorectal cancer and that serological analysis for p53
      antibodies may have some value for patient monitoring. The test has no value for
      prognosis.

PMID- 8985090
TI  - Increased analytical sensitivity of RT-PCR of PSA mRNA decreases diagnostic
      specificity of detection of prostatic cells in blood.
AB  - The diagnostic specificity of the detection of disseminated prostatic cells by
      reverse-transcriptase polymerase chain reaction (RT-PCR) of PSA mRNA was
      investigated. A sensitive nested PCR was developed. In blood samples from 10
      healthy female and 10 healthy male persons examined by RT-PCR, mRNA of PSA was
      detected 3 times in each group. In the groups of patients suffering from benign
      prostate hyperplasia and prostate cancer, 6 of 11 and 5 of 12, respectively, gave
      positive RT-PCR results. With increasing analytical sensitivity of the RT-PCR of
      PSA mRNA, the diagnostic specificity of the assay is decreased. Further
      development of this diagnostic method requires the introduction of the
      quantitative PCR which may make possible discrimination between prostatic and non
      prostatic source of PSA mRNA by quantification.

PMID- 8985091
TI  - The influence of physical activity on lung-cancer risk: A prospective study of
      81,516 men and women.
AB  - Physical activity is inversely related to mortality from respiratory diseases
      including lung cancer. Physical activity improves pulmonary function but its
      impact on lung-cancer risk has not been studied much. During 1972-1978, 53,242
      men and 28,274 women, aged 20 to 49 years, participated in a population-based
      health survey and were followed until 31 December 1991. We observed a total of
      413 men and 51 women with lung cancer. Leisure activity and work activity were
      assessed using a questionnaire in 4 categories. In a sub-cohort, physical
      activity was assessed twice at an interval of 3 to 5 years. Leisure but not work
      activity was inversely related to lung-cancer risk in men after adjustment for
      age, smoking habits, body-mass index and geographical residence (p for trend =
      0.01). Men who exercised at least 4 hours a week had a lower risk than men who
      did not exercise [relative risk (RR) = 0.71; 95% confidence interval (CI) = 0.52
      0.97]. Reduced risk of lung cancer was particularly marked for small-cell
      carcinoma (RR = 0.59; 95% CI = 0.38-0.94) and for adenocarcinoma (RR = 0.65; 95%
      CI = 0.41-1.05), with no association seen for squamous-cell carcinoma. In the sub
      cohort in which physical activity was assessed twice, the risk of lung cancer was
      particularly reduced among men who were most active at both assessments (RR =
      0.39; 95% CI = 0.18-0.85). No consistent association between physical activity
      and lung-cancer risk was observed among women. Our results suggest that leisure
      physical activity has a protective effect on lung-cancer risk in men. The small
      number of incident cases, combined with the narrow range of physical activity
      reported, may have limited our ability to detect an association between physical
      activity and lung cancer in women.

PMID- 8985092
TI  - Human monoclonal antibodies specific for the tumour associated Thomsen
      Friedenreich antigen.
AB  - Five hybridomas producing human monoclonal antibodies (MAbs) of IgA and IgM
      isotypes reacting with the tumour associated TF antigen were generated after in
      vitro immunisation or antigen specific isolation of normal peripheral blood B
      cells using asialoglycophorin, a TF containing antigen. All 5 antibodies produced
      by the hybridomas bound strongly to asialoglycophorin and to synthetic
      glycoprotein containing the TF-epitope, with preference to the beta form (Galb1
      3GalNAc-beta-O-CETE-BSA) as compared to the alpha form (Galbl-3GalNAc-alpha-O-APE
      HSA) in ELISA. Flow cytometry analysis revealed binding to carcinoma cell lines
      of different origin such as breast, colon, pancreas, ovary, bladder, lung and, in
      addition, to some tumour cell lines of haematopoietic origin. Immunohistochemical
      analysis of tumour tissues revealed staining patterns typical for mucins, and the
      antibodies were found to bind to glycoproteins among the MUC-1 positive high m.w.
      fraction shed from a TF antigen positive ovarian carcinoma cell line.

PMID- 8985093
TI  - Effect of all trans-retinoic acid (ATRA) on the adhesive and motility properties
      of acute promyelocytic leukemia cells.
AB  - All trans-retinoic acid (ATRA) induces complete remission in acute-promyelocytic
      leukemia (APL) patients. This study investigated the adhesive properties of APL
      cells for the endothelium and the extracellular matrix, their motility and the
      effect of ATRA on these functions. Blasts from 7 APL patients adhered to resting
      and IL-1-activated endothelium, to the same degree as normal PMN. Adhesion was
      partially mediated by ICAM-1 and, for IL-1-activated endothelium, by VCAM-1 and E
      selectin. These cells showed less adhesiveness for the matrix than PMN, although
      they maintained the same substrate preference: they adhered to fibronectin and
      thrombospondin, but not to laminin and type-IV collagen. Exposure to ATRA in
      vitro (1 microM for 48 to 96 hr) increased the adhesiveness of APL cells; this
      effect was particularly evident in the case of sub-endothelial matrix and
      fibronectin. A similar increment in adhesiveness was observed when comparing
      cells from 2 patients before and after treatment with ATRA. APL cells migrated in
      response to fMLP and motility was increased by ATRA. In conclusion, APL cells
      were less adhesive to the matrix than PMN, but treatment with ATRA considerably
      enhanced their adhesive properties. This could be important in determining the
      efflux of leukemic cells from the bone marrow and their tissue infiltration
      during ATRA therapy.

PMID- 8985094
TI  - Growth inhibition by dominant-negative mutations of the neu-encoded oncoprotein.
AB  - In the present study, kinase-deficient mutants of the neu gene were constructed
      in order to generate dominant-negative receptor molecules, which should abolish
      phosphorylation of receptor complexes. One construct carried a mutation of the
      putative ATP-binding site (K758M), while the other mutant was generated by
      deletion of the kinase domain (ID400). Neither receptor showed phosphorylation by
      in vitro kinase assay. When NIH3T3 fibroblasts were co-transfected by the
      oncogenic neu gene and one of either construct, the transforming effect could be
      partially reversed. Therefore, kinase-negative mutations of the neu-encoded
      receptor seemed to have a dominant-negative effect on the action of the activated
      protein. To test this hypothesis, rat neurinoma cell lines containing oncogenic
      neu genes were transfected with the constructs. Expression of the kinase
      defective mutants and reduced phosphorylation could be detected in different
      clones derived from single transfected cells. Striking growth inhibition and
      reduction of colony formation in soft agar were observed in these cell lines when
      compared with untransfected cells. Thus, kinase-deficient mutants exert a
      dominant-negative effect on phosphorylation of receptor complexes, resulting in a
      reversion of the transformed phenotype.

PMID- 8985095
TI  - In vivo effects of chlorophyllin on the antitumour agent cyclophosphamide.
AB  - Cyclophosphamide (CP) is a potent antitumour agent used against many forms of
      cancer and against certain other diseases. Chlorophyllin (CHL), which is obtained
      by hydrolysis of chlorophyll to remove phytyl alcohol, is an efficient
      antimutagenic agent and has been used as a dietary supplement or to diminish the
      intensity of the discomforting side effects of CP therapy. We undertook to
      determine the antimutagenic effectiveness of CHL against CP in a mouse model and
      to determine whether the antitumour efficacy of CP was compromised in vivo by CHL
      treatment. Experiments utilised CHL administered either in drinking water (1%)
      for 2 days before treatment, or by gavage (200 mg/kg) 2 hr before treatment with
      CP (220 mg/kg). Urinary mutagenicity following CP treatment, as determined by the
      Salmonella/microsome assay, was decreased by both regimes of CHL co-treatment.
      Similarly, the increase in micronuclei in bone marrow polychromatic erythrocytes
      in response to CP was reduced by concomitant CHL treatment. In contrast,
      antitumour efficacy, as determined by growth delay of Colon 38 adenocarcinomas,
      was not diminished by CHL treatment. We conclude that CHL may have beneficial
      effects when used in combination with CP therapy.

PMID- 8985096
TI  - Photobleaching of protoporphyrin IX in cells incubated with 5-aminolevulinic
      acid.
AB  - Protoporphyrin IX (Pp IX) is the main photosensitizer in photochemotherapy with 5
      aminolevulinic acid (ALA). Pp IX is photolabile and the present work shows that
      70-95% of Pp IX in cells is degraded by clinically relevant light exposures (40
      200 J cm(-2) at 630 nm). During light exposure a small yield of
      photoprotoporphyrin, which is also photolabile, is formed. A substantial fraction
      of Pp IX in cells incubated with ALA is bound to proteins. During light exposure
      these binding sites are destroyed, those close to tryptophan residues being the
      most sensitive. The rate of photodegradation of Pp IX in the cells is dependent
      on the initial concentration of Pp IX. The degradation mechanisms are therefore
      not only first order processes. Different degradation rates appear to be related
      to different types of binding sites. During light exposure, Pp IX molecules
      appear to move to different binding sites, evidently sites that are more vital
      for cell survival. Thus, the yield of photoinactivation of the cells, as measured
      per emitted photon of Pp IX fluorescence, increased during light exposure.

PMID- 8985097
TI  - Dendritic epidermal T-cell involvement in induction of CD8+ T cell-mediated
      immunity against an ultraviolet radiation-induced skin tumor.
AB  - Murine epidermis contains 2 distinct cell populations which contribute to the
      skin immune system, Langerhans cells (LC), and dendritic epidermal T cells
      (DETC). LCs are important in the induction of immunity against a wide range of
      antigens; however, the function of DETC is unclear. To investigate the roles of
      these epidermal cells (EC) in protective antitumor immunity, an in vivo model of
      an ultraviolet radiation-induced fibrosarcoma, UV-13-1, was used. Mice were
      immunized with tumor antigen-pulsed EC followed 10 days later by an injection
      into the ear of 10(5) tumor cells, which did not lead to formation of a
      detectable tumor, but was intended to simulate the influence of a developing
      tumor on the ensuing immune response. The mice were then challenged with 2 x
      10(6) viable tumor cells in each flank, sufficient to result in growth of a
      measurable tumor. Protective immunity was induced by DETC, and shown to be long
      lasting, with tumors inoculated 160 days after immunization being effectively
      rejected. The effector cells responsible for protective immunity were CD8+ T
      cells. Delayed-type hypersensitivity generated by tumor antigen-pulsed EC was
      dependent on LCs, with no involvement of DETCs. This response, in contrast to
      that of DETC, required prior culture of EC with GM-CSF, but failed to inhibit
      tumor growth or incidence. Thus DETC and LC can both activate antitumor immune
      responses, although only the DETC-dependent response results in protective
      immunity in the presence of a developing tumor.

PMID- 8985098
TI  - Anti-alpha3 integrin antibody induces the activated form of matrix
      metalloprotease-2 (MMP-2) with concomitant stimulation of invasion through
      matrigel by human rhabdomyosarcoma cells.
AB  - Proteolytic enzymes, such as matrix metalloproteases (MMPs), play a pivotal role
      in cancer invasion and metastasis. Invasive human rhabdomyosarcoma cells (RD)
      secreted proMMP-2 (72-kDa progelatinase). We found that anti-alpha3 and -alpha2
      integrin antibodies induced the activated form of MMP-2 and enhanced proMMP-2
      secretion by RD cells. The effect of anti-alpha2 integrin antibody was less
      prominent than that seen with anti-alpha3 integrin antibody. Moreover, we have
      found that anti-alpha3 and -alpha2 integrin antibodies enhanced RD-cell invasion
      through matrigel (reconstituted basement membrane) by 2.6- and 2.0-fold
      respectively this process was abrogated by neutralizing antibody to MMP-2. These
      data suggest that signaling events induced by anti-alpha3 integrin antibody may
      be involved in RD-cell invasion as a result of modulation of matrix
      metalloprotease expression.

PMID- 8985099
TI  - Mechanisms of escape from CD8+ T-cell clones specific for the HER-2/neu proto
      oncogene expressed in ovarian carcinomas: related and unrelated to decreased MHC
      class 1 expression.
AB  - We have developed an in vitro model to study mechanisms by which ovarian tumor
      cells that over-express the HER-2/neu proto-oncogene escape recognition by TCD8+.
      Nine tumor-specific, HLA A2-restricted TCD8+ clones were isolated from 2 ovarian
      tumor-specific TCD8+ lines derived from tumor-infiltrating or -associated
      lymphocytes. Of these, 2 clones recognized the previously defined HER-2/neu
      epitope E75 (a.a. 369-377) and one recognized the C85 epitope (a.a. 971-979),
      whereas the specificity of the remaining 6 clones was unknown. Three different
      tumor escape variants (EVC8, EVC22 and EVC36) were produced by co-culturing an
      ovarian tumor line over-expressing HER-2/neu with these autologous TCD8+ clones.
      Cell surface expression of HLA A2 was markedly decreased on all 3 escape
      variants, relative to the parental tumor line, while no significant decrease in
      their expression of the HER-2/neu, ICAM-1 or LFA-3 molecules was found. There was
      a correlation between the level of tumor-specific recognition and HLA A2
      expression among the tumor clones isolated from 2 of the escape variants (EVC8
      and EVC36). In contrast, high HLA A2-expressing tumor clones isolated from the
      EVC22 variant, or EVC22 which had regained high HLA A2 expression through IFN
      gamma treatment, were not recognized by the HER-2/neu-specific TCD8+ clone C-22.
      No mutations were found in the cDNA or the genomic DNA derived from the PCR
      product corresponding to a 496 bp fragment including the region coding for the
      E75 epitope of the HER2/neu gene in the EVC22 variant. Collectively, this in
      vitro model underlines the importance of decreased expression of the HLA
      restriction element for escape from tumor-specific TCD8+ but also demonstrates
      that additional mechanisms exist.

PMID- 8985100
TI  - Possible contribution of active MMP2 to lymph-node metastasis and secreted
      cathepsin L to bone invasion of newly established human oral-squamous-cancer cell
      lines.
AB  - We have established human oral-squamous-cancer cell lines, BHY and HN, derived
      from non-metastatic cancer and metastatic cancer respectively. We examined the
      expression of matrix-degrading enzymes and their inhibitors in these cell lines.
      Both cell lines expressed pro-matrix metalloproteinase (MMP)1, proMMP2, proMMP9,
      membrane-type MMP and urokinase-type plasminogen activator. In addition to these
      enzymes, BHY cells secreted proMMP7 and procathepsin L, while HN cells secreted a
      large amount of active MMP2. BHY cells secreted a tissue inhibitor of matrix
      metalloproteinase, TIMP2, but only a trace level of TIMP1. Contrary to BHY cells,
      HN cells secreted TIMP1, but only a trace level of TIMP2. When we inoculated
      these cells into the masseter muscle of nude mice, both types of cell formed
      solid tumors, whose microscopic appearance was identical to that of the original
      tumors. BHY tumors were highly differentiated squamous-cell carcinomas, and
      invasive to the masseter muscle and the mandibular bone. Despite their local
      aggressiveness, BHY tumors did not metastasize to any distant organs. HN tumors
      were poorly differentiated squamous-cell carcinomas, weakly invasive to the
      muscle, but not to the mandibular bone. However, HN tumors frequently
      metastasized to cervical lymph nodes. These results suggest that the net activity
      of MMP2 (active MMP2/TIMP2) and cathepsin L secreted from cancer cells may
      contribute respectively to lymph-node metastasis and to bone invasion by oral
      cancer cells.

PMID- 8985101
TI  - Bacillus Calmette-Guerin mycobacteria stimulate human blood dendritic cells.
AB  - Bacillus Calmette-Guerin (BCG) mycobacteria have been used as adjuvant in the
      active immunotherapy of various human cancers. In addition, dendritic cells,
      which are the most potent antigen-presenting cells, have been shown to be capable
      of initiating anti-tumor immune responses. Here we investigated the effects of
      BCG on dendritic cells cultured from human blood. Addition of BCG resulted in
      rapid homotypic adhesion of dendritic cells. Moreover, BCG concentrations ranging
      from 10(4) to 10(6) bacteria/ml enhanced expression of the dendritic-cell
      maturation antigen CD83 and of the T-cell co-stimulator CD86 (B7-2) in a dose
      dependent manner. Concomitant with the increase of CD83 and CD86 expression, the
      cells lost the ability to capture soluble antigens, as determined by the
      exclusion of fluoresceinated Dextran molecules. Strikingly, the same dosages of
      BCG-bacteria stimulated TNF-alpha-gene transcription and TNF-alpha-protein
      release from dendritic cells in a dose-dependent fashion. BCG infection of
      dendritic cells in the presence of a neutralizing antibody directed against TNF
      alpha inhibited CD83 expression by more than 50% indicating that the BCG-induced
      maturation of dendritic cells was at least partially mediated by dendritic-cell
      derived TNF-alpha. The finding that BCG activates the most potent antigen
      presenting cells reveals a plausible immunological mechanism of the occasionally
      observed anti-tumor activity of BCG.

PMID- 8985102
TI  - Transformation of normal human fibroblasts into immortalized cells with the
      mutant p53 gene and X-rays.
AB  - In vitro cell transformation is a valuable approach for studying the mechanisms
      of multistep carcinogenesis of human cells. Since immortalization is an essential
      step for in vitro neoplastic transformation of human cells, this study addresses
      the question of whether mutant p53 contributes to the immortalization process of
      human cells. The mutant p53 gene (mp53: codon273Arg-His) was introduced into
      normal human fibroblasts (OUMS-24 line) and a G418-resistant clone, OUMS-24/P6
      line, was obtained. This clone showed an extended life span and chromosome
      abnormalities, but senesced at the 79th population doubling level (PDL). When
      these cells were subjected to intermittent X-ray treatment, they became an
      immortalized cell line (OUMS-24/P6X). Although these immortalized cells showed
      chromosome abnormalities, they were not tumorigenic. On the other hand, normal
      OUMS-24 cells into which mp53 had not been introduced were not immortalized by
      the same X-ray treatment. These results indicate that introduction and expression
      of mp53 alone were not sufficient for immortalization of human cells, and that
      mutations of the remaining wild-type p53 or other genes may have been necessary
      for immortalization. In fact, no expression of the wild-type p53 was detected in
      the immortalized cells by RT-PCR. Expression of p21, which is located downstream
      of p53, was remarkably reduced in the immortalized cells, resulting in an
      increase in cdk2 and cdc2 kinase activity. These findings indicate that the p53
      p21 cascade may play some role in the immortalization of human cells. On the
      other hand, there was no significant difference in expression of proteins such as
      Rb, p16, cdk4, cdk6, cyclin A and cyclin D1 between the normal and immortalized
      human fibroblasts.

PMID- 8985103
TI  - Cerebral hemodynamics and cerebral metabolism during cold and warm stress.
AB  - The purpose of this study was to examine if local thermo-applications affect
      central nervous reactions. In a crossover study, six normal, healthy volunteers
      at first received cold packs (Cryogel, 8-12 degrees C; Pino GmbH, Hamburg,
      Germany) and afterwards hot packs (Parafango, 50-60 degrees C; Pino GmbH), and
      another six volunteers started with the hot packs and had the cold packs later;
      both groups administered the hot and cold packs to their thighs. Before, during,
      and after treatment, cerebral blood flow velocity (CBFV) in the middle cerebri
      artery (MCA) was measured continuously by transcranial Doppler sonography,
      whereas cerebral respiratory chain enzyme cytochrome aa3 (cCytaa3) and cerebral
      oxygen saturation (cHbO2) were measured by transcranial near infrared
      spectroscopy in frontal brain tissue. Furthermore, CO2 end-tidal and arterial
      blood pressure (noninvasive) were also measured. Six other volunteers received
      only one treatment; therefore, 15 measurements with cold and 15 measurements with
      hot packs were performed. During application of cold packs, a decrease of cHbO2
      of 10.5% (P < 0.001) and cCytaa3 of 6.7% (P < 0.001) was found, whereas the
      CBFV(MCA) increased significantly (3.9%; P < 0.001) between preliminary and post
      stimulus periods. When cold packs were removed, a significant increase of the
      cHbO2 (16.9%; P < 0.001) and cCytaa3 (9.7%; P < 0.001) was measured. With these
      values, cHbO2 and cCytaa3 showed an overshooting counterreaction beyond the
      initial level. When applying the hot packs, a contrary course of the parameters
      was found. cCytaa3 showed a significant increase of 9.3% (P < 0.001) at the end
      of the stimulus phase and a decrease of 1.9% (P = 0.02) during the post-stimulus
      period. The correlating increase of cHbO2 was significant at 13.7% (P < 0.005).
      At the end of the post-stimulus phase, a significant decrease of cHbO2 at 1.9% (P
      = 0.004) was recorded. With Parafango applications, a significant decrease of
      CBFV(MCA) at 6.9% (P < 0.001) was measured at the end of the stimulus in
      comparison with the preliminary phase. Crossover analysis showed no significant
      period effects and intraindividual changes between period and treatment.
      Therefore, both treatments can be compared within the individual using paired t
      test. Local cold and warm stimuli influence the cerebral hemodynamics and
      cerebral metabolism. Cerebral hemodynamics (CBFV(MCA) in comparison with cerebral
      metabolism (cCytaa3, cHbO2) show opposite reactions under thermo-stress. Of
      special interest is the overshooting counter-regulation of cerebral metabolism
      after cold stimulation. These effects may open new thermotherapeutic aspects in
      central nervous system diseases.

PMID- 8985104
TI  - Physician awareness of rehabilitation costs.
AB  - Containment of health care costs is a pressing national issue. In this study, we
      examined physician knowledge of rehabilitation hospital costs by quantifying
      their awareness of hospital charges. All physicians at a free-standing
      rehabilitation hospital were surveyed. Approximately one-half of the physicians
      responded, including 19 attending and 17 resident physicians. The survey
      addressed three issues: physicians' estimate of the billing fee (hospital charge
      to the patient) for various items; how confident they were of the charge; and how
      frequently they ordered each item. The survey listed 65 items including
      diagnostic testing, drugs, therapies, and equipment. The average error in the
      charge estimates was quite large. For example, it was 52, 48, and 108% for
      hematologic tests, imaging studies, and pharmaceuticals, respectively. Charges
      were underestimated twice as often as they were overestimated. Physicians'
      confidence in their knowledge of these fees was quite low. They indicated that
      they were guessing 80 to 90% of the time, had an idea of the cost for 10 to 20%
      of the items, and were confident in their knowledge for less than 1% of the
      items. There were no significant correlations between accuracy of the charge
      estimates and ordering frequency, actual charge of the item, or experience level
      of the physicians.

PMID- 8985105
TI  - Post-stroke inpatient rehabilitation. I. Predicting length of stay.
AB  - This study was undertaken to identify factors predicting stroke inpatient
      rehabilitation length of stay in an acute inpatient rehabilitation program,
      including occupational therapy, physical therapy, and speech therapy. A cohort of
      152 patients suffering from stroke (76 women and 76 men) voluntarily participated
      in this study. They were recruited from a general hospital in which they had
      received physical rehabilitation. The functional status of patients was observed
      by a physiotherapist, using the Functional Independence Measure(SM). The
      functional status was observed on patient admission to rehabilitation and at 1 wk
      from admission. Post-stroke biologic characteristics, including physical,
      neuropsychological, and clinical characteristics, as well as sociodemographic
      characteristics were also collected. A path analysis, using successive multiple
      linear regressions, was adopted to predict length of stay in rehabilitation.
      Significant predictors of length of stay were age, functional status at 1 wk post
      rehabilitation admission, perceptual status, and balance status. These predictors
      accounted for 43.6% of the total variance in the rehabilitation length of stay.
      Indirect predictors of length of stay were identified as the following:
      functional status at admission, rehabilitation program, motor status,
      communication problems, and medical complications. Functional, biologic, and
      sociodemographic characteristics should be considered simultaneously in the
      prediction of length of stay as well as for the better understanding of the
      stroke rehabilitation process.

PMID- 8985106
TI  - Post-stroke inpatient rehabilitation. II. Predicting discharge disposition.
AB  - This study was undertaken to identify indicators that predict discharge
      disposition after an acute stroke rehabilitation program. A cohort of 152
      incident cases suffering from stroke (76 women and 76 men) voluntarily
      participated in this study. They were recruited from a general hospital in which
      they were participating in a rehabilitation program. Post-stroke biologic,
      sociodemographic, and psychosocial characteristics were considered in our
      analyses. A polychotomous nominal logistic regression analysis was used to
      predict inpatient rehabilitation discharge disposition. The three discharge
      disposition categories were (1) private home, (2) rehabilitation center, and (3)
      long-term care facility. Significant predictors related to the discharge toward a
      rehabilitation center were functional status at admission, presence of social
      support, and gait status. Significant predictors for discharge to a long-term
      care facility were functional status at admission, presence of social support,
      gait status, and presence of medical complications. Functional status measured on
      rehabilitation admission should be considered, in conjunction with the patient's
      social support, gait status, and presence of medical complications, to be
      predictive of post-stroke rehabilitation discharge disposition.

PMID- 8985107
TI  - Statistical methods of computing reference values for side-to-side differences in
      nerve conduction studies.
AB  - This study uses theoretic derivations, statistical simulations, and empirical
      estimations to compare two ways of deriving reference values for side-to-side
      differences in nerve conduction parameters of healthy subjects. The two methods
      involve using the side-to-side differences (STSD) and the absolute values of the
      STSD (AVSTSD). The theoretic derivations showed that the population reference
      value of the AVSTSD is greater than the STSD reference values by 0.18%.
      Simulation studies showed that the AVSTSD yields greater sampling errors than the
      STSD method when establishing the reference values for nerve conduction
      parameters. However, the sampling variability is substantially reduced by using
      study samples of greater than 50, and the differences between the two methods in
      sampling errors are trivial as sample size approaches 100. Using H reflex (HR)
      and extensor digitorum brevis reflex (EDBR) clinical data, the two methods were
      compared. In contrast to the small theoretic differences in reference values, the
      AVSTSD method overestimated the reference value by 0.5 ms for the EDBR and 0.1 ms
      for the H reflex, when using data from a population sample, increasing the type
      II error (reducing sensitivity) for the EDBR. The STSD method is recommended for
      establishment of normal values and for clinical comparisons.

PMID- 8985108
TI  - Hemodynamic and thermal responses to head and neck cooling in men and women.
AB  - Personal cooling systems are used to alleviate symptoms of multiple sclerosis and
      to prevent increased core temperature during daily activities. The objective of
      this study was to determine the operating characteristics and the physiologic
      changes produced by short term use of one commercially available thermal control
      system. A Life Support Systems, Inc. Mark VII portable cooling system and a
      liquid cooling helmet were used to cool the head and neck regions of 12 female
      and 12 male subjects (25-55 yr) in this study. The healthy subjects, seated in an
      upright position at normal room temperature (approximately 21 degrees C), were
      tested for 30 min with the liquid cooling garment operated at its maximum cooling
      capacity. Electrocardiograms and scalp and intracranial blood flows were recorded
      periodically during each test sequence. Scalp, right and left ear, and oral
      temperatures and cooling system parameters were logged every 5 min. Scalp, right
      and left ear canal, and oral temperatures were all significantly (P <0.05)
      reduced by 30 min of head and neck cooling. Oral temperatures decreased
      approximately 0.2-0.6 degrees C after 30 min and continued to decrease further
      (approximately 0.1-0.2 degrees C) for a period of approximately 10 min after
      removal of the cooling helmet. Intracranial blood flow decreased significantly (P
      < 0.05) during the first 10 min of the cooling period. Both right and left ear
      temperatures in the women were significantly lower than those of the men during
      the cooling period. These data indicate that head and neck cooling may be used to
      reduce core temperature to that needed for symptomatic relief of both male and
      female multiple sclerosis patients. This study quantifies the operating
      characteristics of one liquid cooling garment as an example of the information
      needed to compare the efficiency of other garments operated under different test
      conditions.

PMID- 8985110
TI  - Revised trauma score: an additive predictor of disability following traumatic
      brain injury?
AB  - Recent studies have clarified the role of hypoxic-ischemic damage as a secondary
      factor in traumatic brain injury (TBI). Many trauma centers are now consistently
      using the Revised Trauma Score (Glasgow Coma Scale, systolic blood pressure, and
      respiratory rate) to assist with triage of multitrauma patients. This study
      investigated the predictive power of the Revised Trauma Score (RTS) instead of
      the Glasgow Coma Scale (GCS) in determination of disability as measured by the
      Disability Rating Scale (DRS). Data were obtained as part of the National
      Institute for Disability and Rehabilitation Research TBI Model Systems database
      on 501 patients receiving acute medical care and inpatient rehabilitation within
      a coordinated neurotrauma program for treatment of TBI. Initial RTS and GCS were
      obtained on admission to the emergency department, along with the lowest GCS
      measured in the first 24 h. Analysis of initial RTS and GCS demonstrated modest,
      but statistically significant Pearson's correlations with DRS at rehabilitation
      admission (-0.18 and -0.25, respectively) and discharge (-0.22 and -0.24,
      respectively). Lowest GCS within the first 24 h postinjury also failed to show a
      strong relationship with DRS at rehabilitation admission (-0.28) and discharge (
      0.24). Multiple regression analysis performed on RTS subsets for systolic blood
      pressure and respiratory rate did not reveal an added predictive value. Although
      RTS may be important in emergency triage for its ability to predict mortality,
      this study indicates its limited usefulness in prediction of disability.

PMID- 8985109
TI  - Anatomy of the iliolumbar ligament: a review of its anatomy and a magnetic
      resonance study.
AB  - Data of the postmortem studies of the iliolumbar ligament are controversial
      because of the number, complexity, and variability of the structures present in
      the lumbosacral region. The objective of this work was to study the anatomy of
      the iliolumbar ligament to resolve some clinical problems: (1) do anatomic bases
      exist that can explain the lumbar painful syndrome termed "iliolumbar syndrome?"
      (2) do iliolumbar ligament varieties exist that can influence lumbosacral joint
      stability? Magnetic resonance was used to analyze the anatomic structure of the
      iliolumbar ligament of live human beings. Thirty iliolumbar ligaments of 15
      volunteers were analyzed with magnetic resonance. The images were acquired along
      the transversal and coronal planes (respectively, superoinferior and
      anteroposterior). The portion of the iliolumbar ligament originating from the L-5
      transverse process is made up of two bands (anterior and posterior). The anterior
      band is broad and flat and has two different anatomic varieties. Type 1
      originates from the anterior aspect of the inferolateral portion of the L-5
      transverse process and fans out widely before inserting on the anterior portion
      of the iliac tuberosity. Type 2 originates anteriorly, laterally, and posteriorly
      from inferolateral aspect of the L-5 transverse process and fans out before
      inserting on the anterior portion of the iliac tuberosity. The posterior band of
      the iliolumbar ligament originates from the apex of the L-5 transverse process
      and is fusiform. Just before inserting on the anterior margin and apex of the
      iliac crest it widens, assuming the aspect of a small cone. On the transaxial
      plane, the anterior band of the iliolumbar ligament was placed along the
      horizontal line passing through the transverse processes, whereas the posterior
      band formed an angle of approximately 45 to 55 degrees opened posterolaterally
      with this line. On the coronal plane, the spatial disposition of the iliolumbar
      ligament varies greatly with the size of the L-5 vertebra and its position in the
      pelvis: (1) when L-5 is situated low in the pelvis, the bands of the iliolumbar
      ligament are longer and oblique; (2) when L-5 is situated high in the pelvis, the
      bands of the iliolumbar ligament are shorter and horizontal. The insertion manner
      of iliolumbar ligament posterior band in the iliac crest allows us to confirm the
      possibility of existence of the lumbar painful syndrome termed iliolumbar
      syndrome and confirms the possibility of examining its insertional site manually.
      Being accessible manually, various drugs can be injected directly into it or deep
      friction can be applied. This posterior band is thinner than the anterior, with a
      smaller insertional base on the iliac crest, which explains its lesser resistance
      to torsional overloading and also explains the frequency of this painful
      syndrome. It is probable that the spatial disposition of the iliolumbar ligament
      influences its antitorsional role. Further anatomic and biomechanic studies are
      needed.

PMID- 8985111
TI  - Comparison of two injection techniques using botulinum toxin in spastic
      hemiplegia.
AB  - This study sought to test the hypothesis that injections of botulinum toxin type
      A (BTX-A) at the mid belly of the gastrocnemius muscle in spastic hemiplegic
      adults produce superior clinical results to proximal injections directed toward
      the muscular origin. We designed a randomized, double-blind, placebo-controlled
      intervention study at a university tertiary care setting. Seventeen subjects with
      chronic spastic hemiplegic gait were enrolled from a volunteer community sample;
      time range from acute neurologic insult was 0.75 to 31 yr; age range was 19 to 71
      yr; gender consisted of 11 men and 4 women; diagnoses were 12 patients with
      stroke, 2 with traumatic brain injuries, and 1 with a brain tumor. Two subjects
      were withdrawn from the study because of (1) acute vascular occlusion before
      intervention and (2) noncompliance with follow-up visits. After baseline
      measurements, subjects were injected with 50 units of BTX-A (volume, 0.5 cc) into
      the medial or lateral gastrocnemius: (1) proximally at one site near the muscular
      origin; (2) distally at three sites along the mid belly. We measured outcome
      using the Fugl-Meyer score, Ashworth scale, ankle range of motion, and a timed 50
      ft fastest walk. No outcome measures showed a significant effect attributable to
      site of injections. Confounding variables included physical therapy and varying
      duration of illness in the study cohort. We conclude that the results failed to
      support the hypothesis that BTX-A injections at the mid belly of the
      gastrocnemius produced superior functional improvements to injections located
      near the muscular origin using localization techniques described. Additional
      research comparing more precise localization methods for BTX-A injections might
      further establish the importance of electromyographic guidance using BTX-A in
      management of spasticity.

PMID- 8985112
TI  - Hospitalization and discharge outcome of trauma patients sustaining sciatic nerve
      or sciatic branch injuries.
AB  - This study determined the number and severity of injuries, surgeries, and/or
      other complications and their impact on the acute hospital course of a series of
      15 patients sustaining unilateral traumatic sciatic nerve or sciatic branch
      injuries. Outcome measures studied were length of stay, time to ambulate
      independently from admission, starting time for physical therapy, and number of
      physical therapy sessions. Median length of stay (LOS) and time to independent
      ambulation with assistive devices from admission were 12 and 8 days,
      respectively. Seven patients required fasciotomy, five required vascular repair,
      and five sustained fractures of the involved limb. Patients needing a fasciotomy
      had a significantly longer LOS (P < 0.002) and time to ambulate independently (P
      < 0.001), started physical therapy later (P < 0.006), and required more therapy
      sessions (P < 0.007) before independent ambulation was achieved. Patients with a
      vascular repair had a significantly longer LOS (P < 0.049) and time to ambulate
      independently (P < 0.012). These patients trended toward starting physical
      therapy later (P < 0.063) and requiring more therapy sessions (P < 0.109) before
      independent ambulation was achieved. The presence of a fracture in the involved
      limb did not affect outcome variables. The level and severity of nerve injuries
      were variable; therefore, their effects on LOS and ambulation could not be
      determined. These findings suggest that fasciotomies and vascular repairs but not
      fractures adversely affect the acute LOS, time to ambulate independently, start
      of physical therapy, and number of physical therapy sessions in trauma patients
      with sciatic nerve or sciatic branch injury. This information may be useful to
      the consulting physiatrist.

PMID- 8985113
TI  - Recovery of upper limb motor function in tetraplegia with stellate ganglion block
      treatment of reflex sympathetic dystrophy: a case report.
AB  - Recovery of motor function in spinal cord injury usually does not occur beyond 2
      yr from the date of injury and is rare beyond 8 yr. We present a case of a
      gentleman with a right C-5 motor, left T-5 motor, bilateral T-5 sensory
      tetraplegia, sustained after a fall in September 1985, who developed reflex
      sympathetic dystrophy of his right arm. This pain failed to resolve during the
      next 8 yr, despite conservative treatment consisting of range of motion, contrast
      baths, transcutaneous electrical nerve stimulation unit, and tricyclic
      antidepressants. Furthermore, his pain was refractory to dorsal rhizotomy in
      1987. Subsequent follow-up visits documented ongoing pain and weakness of the
      right arm, with a stable injury pattern. Approximately 8 yr after initial injury,
      the patient underwent a series of eight stellate ganglion blocks, with the
      surprising result of improvement in Kendall graded motor function. This
      improvement was enough to represent a change in the motor level of spinal cord
      injury from C-6 to C-7, with a resultant increase in functional abilities. The
      improvement of motor function after stellate ganglion blocks for treatment of
      reflex sympathetic dystrophy is unprecedented and indicates that its aggressive
      treatment in patients with myelopathies may hasten motor recovery and, thus,
      functional gains. Physiologic explanations for this phenomenon include (1)
      resolution of pain inhibition, (2) improvement in disturbed microcirculation, and
      (3) resolution of sympathetic inhibition of mu-motor neurons via internuncial
      neurons.

PMID- 8985114
TI  - Team decision-making in rehabilitation: a commentary.

PMID- 8985115
TI  - Identification of the active gene coding for the metastasis-associated 37LRP/p40
      multifunctional protein.
AB  - A 37LRP/p40 polypeptide is of major interest because it is consistently up
      regulated in cancer cells in correlation with their invasive and metastatic
      phenotype. Furthermore, this polypeptide presents intriguing multifunctional
      properties because it has been characterized as the precursor of the metastasis
      associated 67-kD laminin receptor (67LR) and as a cytoplasmic ribosomal
      associated protein. The isolation of the 37LRP/p40 gene is a prerequisite for
      identifying the molecular mechanisms responsible for the constant up-regulation
      of the 67LR expression in cancer cells. To date, the active 37LRP/p40 gene has
      never been identified in any species due to the existence of multiple pseudogenes
      in most vertebrates genomes. In this study, we report for the first time the gene
      structure and potential regulatory sequences of the 37 LRP/p40 gene. The chicken
      genome was selected to undergo this characterization because it is the only known
      vertebrate that bears a single 37 LRP/p40 gene copy. The 37 LRP/p40 active gene
      is composed of 7 exons and 6 introns and bears features characteristic of a
      ribosomal protein gene. It does not bear a classical TATA box and it exhibits
      several transcription initiation sites as demonstrated by RNase protection assay
      and primer extension. Analysis of potential regulatory regions suggests that gene
      expression is driven not only by the 5' genomic region but also by the 5'
      untranslated and intron 1 sequences. On the basis of gene structure and extensive
      protein evolutionary study, we found that the carboxyterminal domain of the
      protein is a conserved lock-and-key structure/function domain that could be
      involved in the biosynthesis of the higher-molecular-weight 67-kD laminin
      receptor in vertebrates, whereas the central core of the protein would be
      responsible for the ribosome associated function. The first identification of the
      active 37LRP/p40 gene presented in this study is a critical step toward the
      isolation of the corresponding human gene and the understanding of the molecular
      mechanisms involved in the up-regulation of its expression during tumor invasion
      and metastasis.

PMID- 8985116
TI  - Sequence analysis and expression in cultured lymphocytes of the human FOSB gene
      (G0S3).
AB  - G0S3 is a member of a set of putative G0/G1 switch regulatory genes (G0S genes)
      selected by screening cDNA libraries prepared from human blood mononuclear cells
      cultured for 2 hr with lectin and cycloheximide. The sequence shows high homology
      with the murine FOSB gene, which encodes a component of the AP1 transcriptional
      regulator. Comparison of cDNA and genomic sequences reveals a 4-exon structure
      characteristic of the FOS family of genes. Freshly isolated cells show high
      levels of FOSB/G0S3 and FOS/G0S7 mRNAs, which decline rapidly during incubation
      in culture medium. The kinetics of expression suggest that the high initial
      levels are caused by the isolation procedure, and do not reflect constitutive
      expression. In cells preincubated for a day, levels of FOS mRNA reach a maximum
      20 min after the addition of lectin and decline to control levels over the next 3
      hr. Levels of FOSB mRNA reach a maximum 40 min after the addition of lectin and
      decline to control levels over the next 6 hr. In freshly isolated cells, both FOS
      and FOSB mRNAs increase dramatically in response to the protein synthesis
      inhibitor cycloheximide. In preincubated cells, the cycloheximide response is
      decreased, especially in the case of FOSB. These differences in expression of FOS
      and FOSB suggest different roles and regulation. Regions of low base order
      dependent stem-loop potential in the region of the gene are defined. These
      indicate where base order has been adapted for purposes other than stem-loop
      stability (e.g., encoding proteins or gene regulation). Regions of low potential
      in a 68.5-kb genomic segment containing the FOSB gene suggest that the potential
      may help locate genes in uncharted DNA sequences.

PMID- 8985117
TI  - Regulation of tissue inhibitor of metalloproteinases-3 gene expression by
      transforming growth factor-beta and dexamethasone in bovine and human articular
      chondrocytes.
AB  - Physiological and pathological degradation of cartilage extracellular matrix
      (ECM) is regulated by the balance between tissue inhibitors of metalloproteinases
      (TIMPs) and matrix metalloproteinases (MMPs). We examined the potential of
      chondrocytes from normal bovine or human osteoarthritic (OA) cartilage to express
      RNA for the new inhibitor TIMP-3 and studied its regulation by an inducer of
      matrix synthesis, transforming growth factor-beta (TGF-beta). Freshly released
      chondrocytes constitutively expressed three transcripts of TIMP-3 that are
      induced by serum factors. In primary cultures of chondrocytes, one of these
      factors, TGF-beta, increased TIMP-3 mRNA in a dose-dependent fashion that
      required de novo protein synthesis and transcription. TGF-beta did not alter
      stability of the TIMP-3 transcripts in RNA decay time-courses, suggesting a
      transcriptional control. Nuclear run-on assays confirmed increased rate of TIMP-3
      gene transcription by TGF-beta. An antiinflammatory glucocorticoid,
      dexamethasone, inhibited the basal, and suppressed partially the TGF-beta
      inducible, TIMP-3 expression in primary bovine and human chondrocytes. DNA
      sequencing of bovine TIMP-3 cDNA revealed an open reading frame of a 211-amino
      acid protein containing signal peptide and 12 conserved cysteines. The encoded
      protein differed from human TIMP-3 at four positions. The constitutive expression
      and evolutionary conservation of TIMP-3 imply its important function. TIMP-3
      induction by TGF-beta suggests the role of this factor and TIMP-3 in cartilage
      remodeling with important implications for arthritis.

PMID- 8985118
TI  - cDNA cloning of a novel WD repeat protein mapping to the 9q22.3 chromosomal
      region.
AB  - To identify expressed sequences from the candidate genomic region of the nevoid
      basal cell carcinoma syndrome (9q22.3), the CpG island rescue PCR methodology was
      employed on the yeast artificial chromosome (YAC) ICI-8AD8 that contains
      microsatellite marker D9S180. A positive clone (IR10, size 350 bp) was isolated
      by screening a human epidermal cDNA library with the island rescue PCR products
      and mapped back to the 9q22.3 region. To obtain additional sequence information
      from IR10, the rapid amplification of cDNA ends (RACE) methodology was employed.
      Within the longest IR10 RACE product, two segments having similarities with
      coronin, a G-like and actin-binding protein of Dictyostelium discoideum, as well
      as with p57, a recently cloned human actin-binding protein, were revealed. In
      fact, these two segments have properties of typical exons, suggesting that the
      RACE products and clone IR10 represent unspliced pre-mRNAs. Using the RACE
      methodology with primers originating from these two exons, it was shown that they
      splice together and the sequences corresponding to the processed IR10 mRNA were
      revealed. This mRNA maps back to 9q22.3 and furthermore was found to code for a
      novel protein composed of 525 amino acids and containing five WD repeats. The
      presence of the WD repeat motif, considered to function in protein-protein
      interactions, implies that the new protein might have a role in intracellular
      signaling. Moreover, Northern analysis indicated that, in addition to epidermis,
      the brain is a tissue with relatively high levels of expression of this gene.
      Finally, Southern analysis showed a functional conservation of the WD repeat
      protein in various species.

PMID- 8985119
TI  - T antigen of human papovavirus JC stimulates transcription of the POU domain
      factor Tst-1/Oct6/SCIP.
AB  - Human papovavirus JC exhibits a strong tropism for glial cells in vivo. To a
      large extent, this effect is due to the pronounced glia specificity of viral gene
      expression, which is mediated by the specific interaction of glial transcription
      factors such as Tst-1/Oct6/SCIP with viral promoter sequences. Here we show that,
      in return, expression of the glial transcription factor Tst-1/Oct6/SCIP can be
      strongly activated by T antigen, the early gene product of JC virus, in a dose
      dependent manner. In transient transfection experiments, stimulation by T antigen
      was entirely dependent on a 335-bp segment of the Tst-1/Oct6/SCIP gene promoter
      that included the transcriptional start site. The same fragment was also bound by
      purified T antigen in immunoprecipitation assays due to the presence of three
      closely spaced and tandemly oriented GAGGC pentamers. However, when this array of
      pentamers was mutated so that binding of T antigen was strongly reduced, T
      antigen-dependent transcriptional activation remained unaffected. Thus, similar
      to viral late gene expression, transcriptional stimulation of the Tst-1/Oct6/SCIP
      gene by T antigen was not dependent on binding to GAGGC pentamers present within
      the promoter. Nevertheless, our data provide strong support for a model in which
      JC virus influences gene expression of its host cell via its early gene product
      in a manner favourable for its own propagation.

PMID- 8985120
TI  - Chicken ovalbumin upstream promoter-transcription factor, hepatocyte nuclear
      factor 3, and CCAAT/enhancer binding protein control the far-upstream enhancer of
      the rat alpha-fetoprotein gene.
AB  - We have further characterized the most distal of the three alpha-fetoprotein
      (AFP) enhancers required for expression of the AFP gene in fetal hepatocytes and
      yolk sac endodermal cells. Almost total rat AFP enhancer 3 (E3) activity is
      driven by a 160-bp fragment at -6 kb containing three target regions for nuclear
      proteins that cooperate to stimulate transcription from the AFP and the thymidine
      kinase promoters in HepG2 hepatoma cells. Region 1, recently shown to be crucial
      for correct function of the enhancer in liver of transgenic mice, is recognized
      by two sets of transcription factors that bind to partly overlapping sites, 1a
      and 1b, in a noncooperative and nonexclusive manner. Site 1a contains a motif,
      AGGTCA, which is recognized by chicken ovalbumin upstream promoter transcription
      factors (COUP-TFs), but not by hepatocyte nuclear factor 4. Hepatocyte nuclear
      factor 3 (HNF3) and CCAAT/enhancer binding protein (C/EBP), which bind to regions
      2 and 3, respectively, are likely responsible for the liver-specific E3 action.
      They play a key role by acting in synergy. The participation of nuclear receptors
      such as COUP-TFs, with C/EBP and HNF3, in the tight control of the distal AFP
      enhancer is a new, and perhaps key, step toward understanding the regulation and
      function of this enhancer, which may remain active throughout development.

PMID- 8985121
TI  - Xenopus cytochrome b561: molecular confirmation of a general five transmembrane
      structure and developmental regulation at the gastrula stage.
AB  - Cytochrome b561 transports electrons by a novel transmembrane vectoral pathway.
      Using the human cytochrome b561 cDNA probe, the Xenopus cytochrome b561 cDNA has
      been isolated and sequenced. A specific ATG was unambiguously identified because
      the Xenopus sequence has a stop codon 7 amino acids upstream from the initiation
      site ATG. The 741-bp open reading frame encodes a 247-amino-acid protein. The
      position of the initiating ATG site in Xenopus cytochrome b561 is consistent with
      the first ATG site in human and mouse proteins, and with the second of two ATG
      sites in the bovine protein. This result indicates that a five transmembrane
      domain model best represents the conformation of cytochrome b561 in membranes.
      Cytochrome b561 plays a fundamental role in the physiology of all neuroendocrine
      tissues, and the results presented here show that Xenopus cytochrome b561 mRNA is
      specific to neuroendocrine tissues and is developmentally regulated at the
      gastrula stage.

PMID- 8985122
TI  - Structure and the promoter region of the mouse gene encoding the 67-kD form of
      glutamic acid decarboxylase.
AB  - We have cloned and determined the complete structure of the murine gene encoding
      the 67-kD form of glutamic acid decarboxylase (GAD67), the gamma-aminobutyric
      acid synthetic enzyme. Its coding region comprises 18 exons spanning 42 kb of
      genomic DNA. Exon 1 together with 64 bp of exon 2 defines the 5' untranslated
      region of GAD67 mRNA. Exon 18 specifies the protein's carboxyl terminal and the
      entire 3' untranslated region. Exons 7/A and 7/B are solely contained in the
      coding regions of two alternatively spliced bicistronic embryonic mRNAs, which
      code for the truncated embryonic GAD forms. The promoter region (P1)
      corresponding to the main group of transcription initiation sites is devoid of
      TATA and CAAT boxes but has putative binding sites for the transcription factor
      SP1 and is embedded in a large G + C-rich domain of a CpG island, features shared
      by the promoters of constitutively expressed housekeeping genes. Primer extension
      data suggests the existence of additional transcription start sites at 130 bp and
      295 bp upstream from the major initiation site that are utilized less frequently
      in adult brain. The tentative distal promoters (P2 and P3) that correspond to the
      minor start sites resemble tissue-specific promoters with TATA and CAAT-like
      boxes. In 1.3 kb of the 5'-upstream region, we identified several putative
      transcription factor binding sites such as AP2, Hox, E-box, egr-1, and NF-kappaB
      and putative neuronal-specific regulatory elements, including the neuronal
      restrictive silencer element, which may have functional significance in the
      developmental and tissue-specific expression of the GAD67 gene.

PMID- 8985123
TI  - Identification of the promoter for the gene encoding the bifunctional enzyme,
      peptidylglycine alpha-amidating monooxygenase.
AB  - The gene encoding rat peptidylglycine alpha-amidating monooxygenase (PAM)
      contains 26 protein-coding exons. We identified two non-overlapping genomic
      clones encoding the 5' untranslated region (UTR) of the PAM gene. Exon 1 has 69
      nucleotides flanked by perfect splice acceptor and donor sites, with a TATA motif
      25 nucleotides upstream. Exon 0 lacks TATA or CAAT motifs and is embedded in a G
      + C-rich 800-nucleotide CpG island. The major products identified by RNase
      protection initiated in exon 0; only a minority of mRNAs initiated in exon 1. 5'
      rapid amplification of cDNA ends (RACE) identified the same major transcriptional
      start sites in exon 0 in the atrium and neurointermediate pituitary. The 2.0-kb
      fragment upstream of exon 0 and the 1.3-kb fragment upstream of exon 1 were
      placed upstream of a luciferase-based reporter gene in both sense and antisense
      orientations. Expression of luciferase was observed in neuroendocrine and
      nonneuroendocrine cells with both sense constructs. A 0.2-kb fragment of the exon
      0 PAM promoter containing multiple GC box elements supported expression of
      luciferase activity in all cell types. Expression of reporter genes in cells that
      do not normally express PAM suggests a need for more upstream or intronic
      information, a role for methylation, or a need for chromatin scaffolding for
      tissue-specific expression of the endogenous gene.

PMID- 8985124
TI  - Guinea pig preprodynorphin mRNA: primary structure and regional quantitation in
      the brain.
AB  - We isolated and sequenced genomic and cDNA clones of the guinea pig
      preprodynorphin (ppDyn) mRNA. The sequence of ppDyn mRNA was deduced from a
      combination of genomic and cDNA clones: The primary structure of two coding exons
      was derived from a genomic clone and 5' and 3' untranslated sequences were
      obtained using rapid amplification of cDNA ends (RACE). The predicted mRNA of
      2,350 nucleotides coincides well with the size of transcripts in Northern blot
      analyses of RNA from different brain regions. The deduced amino acid sequence of
      guinea pig ppDyn shares 70%, 68%, and 61% identity to porcine, human, and rat
      ppDyn, respectively. The 5' untranslated sequences of guinea pig hippocampal and
      adrenal ppDyn mRNA are identical; both contain sequences of exon I and, like
      porcine mRNA, lack an exon (exon II) present in human and rat mRNA. Quantitative
      solution hybridization RNase protection analysis of total RNA from selected
      guinea pig brain regions was performed. The nucleus accumbens was found to have
      the greatest abundance of ppDyn mRNA, followed by caudate putamen, hippocampus,
      hypothalamus, amygdala, frontal cortex, olfactory bulb, and pons/medulla.

PMID- 8985125
TI  - Construction of portable intron cassettes for the delivery and expression of
      foreign genes.
AB  - The use of viral vectors to deliver foreign genes offers some promise of
      generating new and more efficacious vaccines. However, the insertion of foreign
      genes into viral genomes often results in the insertional mutagenesis of one or
      more genes that adversely affect replication. In an attempt to overcome this
      problem, we constructed two portable intron cassettes. The cassettes were derived
      from the adenovirus late leader 1 intron and were cloned into either the
      chloramphenicol acetyltransferase (CAT) gene or the LacZ gene of Escherichia
      coli. The intron cassettes were transfected into chicken embryo fibroblasts
      (CEFs) and the cell lysates were later assayed for either beta-galactosidase
      (beta-Gal) or CAT activity. The first intron cassette (type A) contained flanking
      adenovirus exon sequences. Consequently, the flanking adenovirus exon sequences
      remained in the spliced transcript. With the type A intron inserted in the
      correct orientation for splicing, CAT activity was not diminished. However, in
      the reverse orientation, no CAT activity could be detected. The second intron
      cassette (type B) had the splice donor and splice acceptor sites converted to the
      blunt-end restriction endonuclease sites Pml I and Pvu II, respectively. The
      blunt-end restriction endonuclease sites enabled the portable intron to be
      removed from the flanking adenovirus exon sequences and inserted into any blunt
      end restriction endonuclease site in the recipient gene. After splicing, no
      adenovirus exon sequences remained in the recipient gene's RNA transcript. To
      demonstrate its usefulness, an insertion cassette was made by cloning the E. coli
      LacZ gene into a multiple cloning site within the type B intron. The insertion
      cassette was then cloned into a Pvu II site in the middle of the CAT gene.
      Following transfection in CEFs, high levels of both CAT and beta-Gal were
      detected, demonstrating that both genes were properly transcribed and translated.

PMID- 8985126
TI  - Cloning and sequence analysis of the human MG160, a fibroblast growth factor and
      E-selectin binding membrane sialoglycoprotein of the Golgi apparatus.
AB  - The amino acid sequence of MG160, a membrane sialoglycoprotein of the medial
      cisternae of the rat Golgi apparatus, is more than 90% identical with CFR, a
      fibroblast growth factor (FGF) binding protein of chicken membranes, and with ESL
      1, a ligand for E-selectin of plasma membranes of myeloid cells; furthermore,
      MG160, isolated by immunoaffinity chromatography from rat brain membranes, binds
      to basic FGF. The gene for MG160 has been assigned to human chromosome 16q22-23.
      To characterize this protein further in the human, its cDNA was cloned and
      sequenced. The protein has a large luminal domain composed of an initial proline
      glutamine-rich segment, encoded by an uninterrupted exonic sequence of several
      CAG-CAA repeats. Expansion of CAG repeats has been implicated in the etiology of
      several neurodegenerative diseases. The proline-glutamine-rich segment is
      followed by 16 cysteine-rich repeats that contain five potential asparagine
      linked glycosylation sites, which are conserved in the human, rat, mouse, and
      chicken. The large intralumenal domain of the protein is followed by a single
      transmembrane domain and a 13-amino-acid cytoplasmic carboxy-terminal tail, which
      is identical to that in the chicken, rat, and mouse. The overall amino acid
      identifies between MG160, CFR, and ESL-1 range from 88% to 95%. In several human
      fetal and adult tissues, three mRNA transcripts for MG160 of 10 kb, 5 kb, and 3.8
      kb were identified by Northern blot analysis of poly(A)-selected mRNAs. These
      transcripts may represent alternatively spliced mRNAs of the protein or mRNAs
      encoding closely related proteins of the Golgi apparatus and/or plasma membranes.

PMID- 8985127
TI  - Immunohistochemical signal amplification by catalyzed reporter deposition and its
      application in double immunostaining.
AB  - The biotinyl-tyramide substrate of the horseradish peroxidase enzyme has been
      recently introduced to amplify immunohistochemical signals. We applied either
      fluorochromeor biotin-conjugated tyramine to improve the detection of different
      antigens in sections of rat stomach, pancreas, and hypothalamus. A ten- to 100
      fold increase in staining efficiency was achieved, depending on the antibody,
      with either fluorescent or peroxidase detection systems. The amplification method
      was particularly useful for increasing a weak signal of conventional
      immunostaining caused by suboptimal tissue fixation. At a very low concentration
      of the primary antibody, the antigen can no longer be detected by a conventional
      fluorescent secondary antibody but is still detectable after amplification. When
      an antibody is used at this very low concentration and is detected by a
      fluorescent amplification method, another primary antibody, raised in the same
      host species, can be used and demonstrated with a different fluorochrome in
      subsequent conventional immunostaining of the same section. In this way it
      becomes possible to immunostain the same section with two different primary
      antibodies raised in the same host species. Samples for such double
      immunostaining are demonstrated here using pairs of monoclonal antibodies (to
      tyrosine hydroxylase and oxytocin) in the hypothalamus and polyclonal antibodies
      (to glucagon and neurofilament M) in sections of rat pancreas. Because in many
      cases the availability of antibodies is limited, the amplification method can be
      a quick and efficient tool for double immunostaining with antibodies from the
      same host species.

PMID- 8985128
TI  - Analysis of mitochondrial morphology and function with novel fixable fluorescent
      stains.
AB  - Investigation of mitochondrial morphology and function has been hampered because
      photostable, mitochondrion-specific stains that are retained in fixed,
      permeabilized cells have not been available. We found that in live cell
      preparations, the CMXRos and H2-CMXRos dyes were more photostable than rhodamine
      123. In addition, fluorescence and morphology of mitochondria stained with the
      CMXRos and CMXRos-H2 dyes were preserved even after formaldehyde fixation and
      acetone permeabilization. Using epifluorescence microscopy, we showed that CMXRos
      and H2-CMXRos dye fluorescence fully co-localized with antibodies to subunit I of
      cytochrome c oxidase, indicating that the dyes specifically stain mitochondria.
      Confocal microscopy of these mitochondria yielded colored banding patterns,
      suggesting that these dyes and the mitochondrial enzyme localize to different
      suborganellar regions. Therefore, these stains provide powerful tools for
      detailed analysis of mitochondrial fine structure. We also used poisons that
      decrease mitochondrial membrane potential and an inhibitor of respiration complex
      II to show by flow cytometry that the fluorescence intensity of CMXRos and H2
      CMXRos dye staining responds to changes in mitochondrial membrane potential and
      function. Hence, CMXRos has the potential to monitor changes in mitochondrial
      function. In addition, CMXRos staining was used in conjunction with spectrally
      distinct fluorescent probes for the cell nucleus and the microtubule network to
      concomitantly evaluate multiple features of cell morphology.

PMID- 8985130
TI  - mRNA expressions of TIMP-1, -2, and -3 and 92-KD type IV collagenase in early
      human placenta and decidual membrane as studied by in situ hybridization.
AB  - Cytotrophoblasts of early placenta invade the decidual membrane, gestational
      endometrium, and spiral arteries during early pregnancy. Unlike tumor invasion,
      this physiological invasion is well controlled, although its molecular mechanisms
      are largely unknown. We have previously shown that cytotrophoblasts synthesize
      significant mRNAs for 72-KD Type IV collagenase, laminin, and Type IV collagen,
      proteins implicated in extracellular matrix turnover and migration. In this study
      we used in situ hybridization and immunohistochemistry to investigate the mRNA
      expression pattern of 92-KD Type IV collagenase and the matix metalloproteinase
      inhibitors TIMP-1, TIMP-2, and TIMP-3 in early human placenta and decidual
      membrane. mRNAs for 92-KD Type IV collagenase, TIMP-1, TIMP-2, and TIMP-3 were
      found in the cells of cytotrophoblastic columns, the endothelial and fibroblastic
      stromal cells of villi, and the large decidualized cells of decidual membrane.
      TIMP-1 expression was notably accentuated in the fibroblasts of fibrotic villi.
      In the decidual membrane, the signals for 92-KD Type IV collagenase and TIMP-1
      mRNA were particularly strong around the glandular structures. The trophoblastic
      epithelium of villi and the epithelial cells of decidual glands showed a signal
      for 92-KD Type IV collagenase and TIMP-2, but not for TIMP-1 or TIMP-3. The
      coincidental expression of the proteolytic 92-KD Type IV collagenase and
      inhibitors TIMP-1, TIMP-2, and TIMP-3 generally in the same cells suggests that
      the activity of 92-KD Type IV collagenase, which is regulated by TIMPs, plays an
      important role in placental tissue organization and in the invasion of
      trophoblastic cells into the uterine wall.

PMID- 8985129
TI  - Upregulation of dynamin II expression during the acquisition of a mature
      pancreatic acinar cell phenotype.
AB  - Members of the dynamin superfamily are GTPases which have been shown to support
      receptor-mediated endocytosis in vivo and bind to growth factor receptor
      associated proteins in vitro. In acinar cells of the pancreas, receptor-mediated
      endocytosis is very important for the recycling of membranes after secretory
      granule release. Therefore, characterization of the molecular machinery
      responsible for this process is critical for a better understanding of this
      phenomenon. In this study we sought to determine the expression pattern of the
      endocytic GTPase dynamin II during pancreatic acinar cell differentiation in
      developing rat embryos and in dexamethasone-treated AR42J cells using Western
      blot, Northern blot, and immunocytochemical analyses. During pancreatic
      development, dynamin immunoreactivity is almost undetectable until day E17 but
      undergoes significant upregulation in acinar cells starting at E18. In addition,
      the levels of dynamin mRNA and protein in AR42J cells increase approximately
      threefold during dexamethasone-induced acinar differentiation. The increase in
      dynamin levels that occurs in both embryonic pancreatic cells and dexamethasone
      treated AR42J cells correlates with the establishment of a more differentiated
      acinar phenotype. Therefore, these results suggest a potential role for dynamin
      in supporting receptor-mediated endocytosis in mature pancreatic acinar cells.

PMID- 8985131
TI  - Microfibril-associated glycoprotein-1 (MAGP-1) is specifically located on the
      beads of the beaded-filament structure for fibrillin-containing microfibrils as
      visualized by the rotary shadowing technique.
AB  - This study used immunoelectron microscopic techniques to define the
      ultrastructural location of MAGP-1 on the fibrillin-containing microfibrils of
      the ocular zonule. A specific anti-MAGP-1 monoclonal antibody (MAb), 11B, was
      produced that did not crossreact with fibrillin-1 or other microfibrillar
      proteins. MAb 11B was shown by immunofluorescence to localize intensely to
      zonular tissue. Postembedding immunoelectron microscopy showed that MAGP-1 was
      associated with microfibrils throughout the zonule, with the exception of a
      narrow band of microfibrils at the junction with the lens capsule. With
      preembedding labeling, the anti-MAGP-1 MAb was found to localize in a
      crossbanding pattern, at intervals of about 50 nm, to microfibrils throughout the
      zonule and along bundles of microfibrils in surrounding vitreous tissue. Rotary
      shadowing of isolated microfibrils showed a "beads on a string" morphology with a
      periodicity of about 50 nm. With immunogold labeling, the anti-MAGP-1 antibody
      specifically localized on the beads in a symmetrical manner. Occasionally two
      gold partides were attached to the same bead, suggesting that multiple MAGP-1
      molecules were present in the structure. The results indicate that MAGP-1 is
      intimately and regularly associated with the bead regions of fibrillin-containing
      microfibrils. The findings are consistent with a major structural role for MAGP-1
      in microfibril biology.

PMID- 8985132
TI  - Histochemical and immunohistochemical detection of neurons that produce nitric
      oxide: effect of different fixative parameters and immunoreactivity against non
      neuronal NOS antisera.
AB  - This study focused on two points concerning the histochemical and
      immunohistochemical detection of neurons that produce nitric oxide (NO): (a) the
      effect of fixation and other methodological parameters on the staining pattern of
      both NADPH-diaphorase (NADPH-d) histochemistry and nitric oxide synthase (NOS)
      immunohistochemistry, and (b) the possibility that neurons display
      immunoreactivity against NOS antisera obtained from non-neuronal sources. Frontal
      sections of rat brains, fixed with 4% paraformaldehyde according to different
      protocols, were processed for single and double labeling using NADPH-d
      histochemistry and neuronal (nNOS), macrophagic (macNOS), and endothelial (eNOS)
      NOS immunohistochemistry. Our results show that variations in the fixative
      schedule, even within standard parameters, produce qualitative and quantitative
      changes in NADPH-d labeling. The effect of fixative on weakly stained neurons is
      different from that on heavily stained neurons. In subfixed brains, a large
      number of NOS-positive neurons lose their NADPH-d activity, whereas NOS
      immunolabeling remains unaltered. This finding may be particularly interesting in
      morphological studies that compare NADPH-d activity under experimental conditions
      that can affect brain perfusion. On the other hand, many cortical and subcortical
      neurons show macNOS immunoreactivity, most of it colocalized with nNOS.

PMID- 8985133
TI  - Expression of retinoic acid receptor proteins in basal cell carcinomas: an
      immunohistochemical analysis.
AB  - We analyzed immunohistochemically the expression of RAR proteins in basal cell
      carcinomas (BCCs; n = 15) in situ. The labeling pattern for the different types
      of RARs was compared with the staining pattern of the proliferation marker Ki-67
      in the same tumors. We found strong immunoreactivity for RAR-alpha and moderate
      immunoreactivity for RAR-gamma in all BCCs analyzed, whereas no or very weak
      staining for RAR-beta protein was detected. In contrast to RAR-gamma, which
      revealed no or only marginal differences in staining intensities, RAR-alpha
      immunoreactivity was consistently stronger in BCCs compared to adjacent
      unaffected epidermis. In general, labeling of BCCs for RAR-alpha and RAR-gamma
      was pronounced in cells of the palisade and peripheral cells, whereas staining in
      the center of the tumors was heterogeneous. Eleven of the 15 BCCs analyzed
      revealed no visual correlation in comparing labeling patterns for RAR-alpha and
      RAR-gamma with the labeling pattern for Ki-67. In four specimens, expression of
      RAR-alpha, RAR-gamma, and Ki-67 proteins was confined to peripheral tumor cells.
      Our findings indicate that (a) RAR-alpha and RAR-gamma proteins are, in contrast
      to RAR-beta, strongly expressed in BCCs; (b) expression of RAR-alpha is
      upregulated in BCCs compared to keratinocytes of uninvolved epidermis; and (c)
      BCCs may be targets for potentially preventive or therapeutic treatment with RAR
      alpha- or RAR-gamma-selective retinoic acid metabolites.

PMID- 8985134
TI  - Localization of transglutaminase in hippocampal neurons: implications for
      Alzheimer's disease.
AB  - The purpose of this investigation was to identify and localize tissue
      transglutaminase (TGase) within neurons from the hippocampi of normal aged
      individuals and of those with confirmed Alzheimer's disease (AD). This enzyme may
      be a factor in the molecular mechanisms of neurodegeneration and formation of
      insoluble macromolecular complexes found in the neurons of normal aged and AD
      brain tissue. An antibody made to the extracellular TGase, coagulation factor
      XIIIa, was found to be specific for purified intracellular guinea pig liver
      tissue TGase. The specificity for liver tissue TGase has enabled us to identify
      tissue TGase(s) within rat hippocampal neurons and within neurons from normal
      aged and AD hippocampal tissues. Degenerating neurons from the AD hippocampus,
      compared to neurons from the normal aged hippocampus, exhibited increased
      immunoreactivity for TGase and demonstrated co-labeling for PHF1 and anti-TGase.
      Our results suggest that TGase may be associated with the neurofibrillary
      degeneration observed in AD, thereby implicating TGase as a potential factor in
      the pathogenesis of Alzheimer's disease.

PMID- 8985135
TI  - Ontogeny of Clara cell-specific protein and its mRNA: their association with
      neuroepithelial bodies in human fetal lung and in bronchopulmonary dysplasia.
AB  - Clara cell-specific 10-KD protein (CCSP) is an abundant product of nonciliated
      bronchiolar epithelial (Clara) cells in the lung. We have determined the temporal
      spatial distribution of CCSP and its mRNA in developing human lung and in
      neonatal lung disease, using immunohistochemistry and in situ hybridization. CCSP
      immunoreactivity was found in nonciliated bronchiolar epithelial cells from 12
      weeks of gestation onward. Tracheal and bronchial epithelia showed positive
      immunoreactivity at each gestational week after 15 weeks and 14 weeks,
      respectively. CCSP mRNA was seen in the bronchial and bronchiolar epithelia from
      16 weeks onward and was detected in the trachea from 19 through 23 weeks of
      gestation. CCSP immunoreactivity and mRNA were present in nonciliated single
      cells of bronchial and bronchiolar epithelia in fetuses and in infants with and
      without lung disease. CCSP- and CCSP mRNA-containing epithelial cells also formed
      dusters around neuroepithelial bodies (NEBs), especially at airway branch points,
      suggesting that NEBs and Clara cells might interact during development and during
      pulmonary regeneration. Because of evidence of overlapping of some but not all
      cells expressing CCSP, SP-A, and pro-SP-B during lung development, a common cell
      lineage is proposed, with subsequent divergence of phenotypes.

PMID- 8985136
TI  - Immunoelectron microscopic localization of vimentin in sustentacular cells of the
      carotid body and the adrenal medulla of guinea pigs.
AB  - The sustentacular cells of the carotid body and the adrenal medulla of guinea
      pigs were studied by light and electron microscopic immunohistochemistry and
      compared with the Schwann or satellite cells of the peripheral nervous system. In
      the peripheral nervous system, neurons were immunoreactive for protein gene
      product (PGP) 9.5, whereas Schwann cells or satellite cells were immunoreactive
      for S-100 protein and vimentin. Vimentin immunoreactivity was detected on the
      intermediate filaments of the Schwann cells by post-embedding immunogold
      labeling. In the carotid body and the adrenal medulla, glomus cells or chromaffin
      cells were dosely enveloped by the sustentacular cells, which protruded long
      cytoplasmic processes and had some axons embedded in them, as in Schwann cells.
      The glomus cells or chromaffin cells expressed immunoreactivity for PGP 9.5,
      whereas the sustentacular cells expressed immunoreactivity for S-100 protein and
      vimentin. The sustentacular cells were characterized by the presence of abundant
      intermediate filaments on which immunogold particles for vimentin were densely
      located. From these results, it is concluded that the sustentacular cells closely
      resemble glial cells of the peripheral nervous system in immunohistochemical,
      ultrastructural, and also functional properties, and may belong to the glial
      lineage, originating from the neural crest.

PMID- 8985137
TI  - Relationship between immunostaining intensity and antigen content in sections.
AB  - We studied the relationship between staining intensity of immunohistochemical
      reaction and antigen content in sections. Alpha-fetoprotein (AFP) and albumin in
      sections cut from livers of newborn, 5-, 10-, 20-, and 60-day-old rats were
      examined as examples. First, we compared average immunostaining intensity (sum of
      specific absorbance in pixel/number of pixels) measured by image processing (IP),
      with antigen content measured by immunochemical assay to determine whether the
      intensity is proportional to antigen content. The intensity of AFP was
      proportional to the antigen content, whereas that of albumin was not.
      Subsequently, the antigen preservation test was carried out to determine whether
      the intensity was decreased by fixation and, if so, which type of decrease
      (proportional or disproportionate) occurred. Thereafter, antigen content in the
      same portion in the same immunostained section was measured by the
      microphotometric (MP) method followed by the IP method, because the MP method
      gives a low average antigen content when a decrease in antibody binding occurs in
      sections, whereas the average antigen content measured by the IP method is
      unchanged. The intensity of AFP decreased primarily by a proportional decrease in
      antigenicity during fixation. However, the intensity of albumin decreased not
      only by a proportional decrease during fixation but also by a disproportionate
      reduction in antibody binding during immunostaining or before fixation. The
      results indicate that AFP content in sections is measurable by quantitative
      immunohistochemical methods, whereas albumin content is not.

PMID- 8985138
TI  - Phagocytotic processing of apoptotic bodies of transitional ameloblasts by MHC
      Class II-expressing macrophages in rat incisor.
AB  - We examined the processing of apoptotic ameloblast fragments at the transitional
      stage by immunocytochemistry and electron microscopy. Both macrophages and
      epithelial cells in the enamel organ ingested apoptotic bodies. MHC Class II
      antigen expression and the phagolysosomal nature of the macrophages were further
      examined by immunoelectron microscopy using OX6 and ED1 antibodies followed by
      HRP- or gold-conjugated secondary antibodies. The results showed that macrophages
      in the enamel organ at the transitional stage expressed MHC Class II antigens at
      their plasma membranes and that the same cells contained apoptotic fragments in
      ED1-positive vacuoles. We suggest that diverse immunological responses, such as
      the self-antigen presentation, may be invoked in the process of apoptosis.

PMID- 8985139
TI  - Basement membrane abnormalities in human eyes with diabetic retinopathy.
AB  - Vascular and parenchymal basement membranes (BMs) are thickened in diabetes, but
      alterations in individual BM components in diabetic eyes, especially in diabetic
      retinopathy (DR), are obscure. To identify abnormalities in the distribution of
      specific constituents, we analyzed cryostat sections of human eyes obtained at
      autopsy (seven normal, five diabetic without DR, and 13 diabetic with DR) by
      immunofluorescence with antibodies to 30 BM and extracellular matrix components.
      In non-DR eyes, no qualitative changes of ocular BM components were seen. In some
      DR corneas, epithelial BM was stained discontinuously for laminin-1,
      entactin/nidogen, and alpha3-alpha4 Type IV collagen, in contrast to non-DR
      corneas. Major BM alterations were found in DR retinas compared to normals and
      non-DR diabetics. The inner limiting membrane (retinal BM) of DR eyes had
      accumulations of fibronectin (including cellular) and Types I, III, IV (alpha1
      alpha2), and V collagen. The BM zone of new retinal blood vessels in
      neovascularized areas accumulated tenascin and Type XII collagen, whereas normal,
      diabetic, and adjacent DR retinas showed only weak and irregular staining. In
      preretinal membranes, perlecan, bamacan, and Types VI, VIII, XII, and XIV
      collagen were newly identified. Diabetic BM thickening appears to involve
      qualitative alterations of specific BM markers at an advanced disease stage, with
      the appearance of DR.

PMID- 8985140
TI  - Subcellular localization of SV2 and other secretory vesicle components in PC12
      cells by an efficient method of preembedding EM immunocytochemistry for cell
      cultures.
AB  - We demonstrated the subcellular localization of SV2, a transmembrane protein
      associated with neuroendocrine secretory vesicles, in NGF-treated PC12 cells by
      preembedding EM immunocytochemistry (ICC), using a small gold probe followed by
      silver enhancement. The use of a multiwell chamber slide substantially improved
      the efficiency of the preembedding EM ICC procedures for cell cultures. The
      advantages and related caveats of this method are discussed. SV2 was distinctly
      localized on dusters of synaptic vesicles and large dense-cored vesicles (LDCV).
      The distribution of SV2 on these two types of secretory vesicles was compared
      quantitatively to that of another secretory vesicle-associated transmembrane
      protein, synaptophysin. In cultures under similar experimental conditions, the
      ratio of SV2 vs synaptophysin ICC staining on synaptic vesicle dusters was about
      1:1, whereas it was about 9:1 on LDCV membranes. Furthermore, whereas SV2 is
      localized on the membranes of the LDCVs, chromogranin A, an acidic protein in
      secretory granules, is clearly in the core of the LDCVs. This is the first
      demonstration of these two antigens in such dose (approximately 20 nm) yet
      distinct compartments within a single organelle.

PMID- 8985141
TI  - Stage-specific expression of RESP18 in the testes.
AB  - RESP18 (regulated endocrine-specific protein of 18 KD) is an endoplasmic
      reticulum (ER) protein that was identified by coordinate dopaminergic regulation
      with pro-opiomelanocortin in the rat neurointermediate pituitary. Many attributes
      of RESP18 suggest an important function in neuroendocrine cells. Several
      neuropeptides, growth factors, and enzymes involved in biosynthesis of classical
      chemical neurotransmitters, have been identified in germ cells, Sertoli cells,
      and spermatozoa. In this study, screening of reproductive tissues revealed high
      levels of RESP18 protein and mRNA in the testes but not in ovaries or epididymis.
      The testes and sperm expressed 18-KD RESP18 and a unique 19-KD isoform. To better
      understand RESP18 expression in the testes, we have examined the stages of the
      cycle of the seminiferous epithelium by immunohistochemistry and Western blot
      analyses. Immunohistochemical analysis showed that RESP18 protein was expressed
      exclusively in spermatocytes and maturing spermatids. RESP18 protein was
      expressed at high levels in Step 1-8 round spermatids, in which the PC4
      prohormone convertase, nerve growth factor, and proenkephalin are also expressed.
      Western blots, Northern blots, and indirect immunofluorescence staining
      demonstrated RESP18 expression in sperm.

PMID- 8985142
TI  - Simultaneous in situ detection of mRNA and apoptotic cells by combined
      hybridization and TUNEL.
AB  - We established a new method to allow simultaneous in situ detection of mRNA
      expression and apoptotic DNA fragmentation in paraffin-embedded tissue sections.
      We used human thymic tissue to perform in situ hybridization with a digoxigenin
      labeled CD95 (APO-1/Fas) ligand (CD95L)-specific probe followed by TdT-mediated
      biotin dUTP nick end-labeling (TUNEL) of apoptotic DNA fragments. Bound probes
      were visualized by an immunogold-silver enhancement technique and fragmented DNA
      was detected with a streptavidin-peroxidase system. This double labeling
      technique produced a distinct, dark cytoplasmic staining of CD95L mRNA-expressing
      cells and an intense red nuclear precipitate in apoptotic cells or bodies. This
      technique will be a useful tool for microtopographical analysis of apoptosis
      related gene expression.

PMID- 8985143
TI  - Removal of substrate inhibition in a lactate dehydrogenase from human muscle by a
      single residue change.
AB  - High concentrations of ketoacid substrates inhibit most natural hydroxyacid
      dehydrogenases due to the formation of an abortive enzyme-NAD+-ketoacid complex.
      It was postulated that this substrate inhibition could be eliminated from lactate
      dehydrogenases if the rate of NAD+ dissociation could be increased. An analysis
      of the crystal structure of mammalian LDHs showed that the amide of the
      nicotinamide cofactor formed a water-bridged hydrogen bond to S163. The LDH of
      Plasmodium falciparum is not inhibited by its substrate and, uniquely, in this
      enzyme the serine is replaced by a leucine. In the S163L mutant of human LDH-M4
      pyruvate inhibition is, indeed, abolished and the enzyme retains high activity.
      However, the major contribution to this effect comes from a weakening of the
      interaction of pyruvate with the enzyme-coenzyme complex.

PMID- 8985144
TI  - Molecular cloning, expression and tissue distribution of a chicken angiotensin II
      receptor.
AB  - A cDNA encoding a chicken angiotensin II receptor from adrenal gland was isolated
      to serve as a molecular tool to study the role of AngII in avian embryonic
      development. This cDNA, sharing a high homology with another avian receptor
      (turkey), encodes a protein of 359 amino acids with 75% sequence identity with
      the mammalian type 1 receptor. Transient expression has revealed pharmacological
      properties distinct from mammalian receptors and a functional coupling leading to
      the increase in inositol phosphate production. The AngII receptor mRNA is
      expressed in classical target organs for AngII (adrenal gland, heart, kidney)
      and, interestingly, in endothelial cells where it may mediate the peculiar
      vasorelaxation effect of AngII in the chicken.

PMID- 8985145
TI  - Complete synthesis of 3'-sialyl-N-acetyllactosamine by regioselective
      transglycosylation.
AB  - Transglycolytic synthesis of 3'-sialyl-N-acetyllactosamine by sequential use of
      beta-galactosidase from Bacillus circulans and trans-sialidase from Trypanosoma
      cruzi was described. These reactions depicted the first complete synthesis of a
      biologically important oligosaccharide with high regioselectivity avoiding use of
      glycosyltransferases and NDP sugars.

PMID- 8985146
TI  - Synergistic effects of transforming growth factor-beta on the expression of c
      fms, macrophage colony-stimulating factor receptor gene, in vascular smooth
      muscle cells.
AB  - Vascular smooth muscle cells (SMC) transform to foam cells in the process of
      atherosclerosis. We have reported that SMC derived from the intima of
      atherosclerotic lesions express c-fms, macrophage colony-stimulating factor
      receptor gene, which is not normally expressed in medial SMC. In the present
      study, we demonstrated that transforming growth factor-beta (TGF-beta)
      synergistically induced expression of c-fms in the presence of platelet-derived
      growth factor-BB in human medial SMC, a level comparable to that observed in the
      intima. The induction of c-fms was not inhibited by protein kinase C (PKC)
      inhibitor, suggesting that TGF-beta induces c-fms via a PKC-independent pathway.
      These results suggest that TGF-beta plays an important role in the phenotypic
      change of smooth muscle cells to macrophage-like cells in the process of
      atherosclerosis.

PMID- 8985147
TI  - Interaction of G protein Gbetagamma dimers with small GTP-binding proteins of the
      Rho family.
AB  - Gbetagamma dimers of heterotrimeric G proteins have been shown to be important
      for the translocation of cytosolic proteins to membranes. The involvement of
      Gbetagamma in those signaling processes mediated by small GTP-binding proteins of
      the Rho family was studied using purified proteins. We showed specific binding of
      bovine brain Gbetagamma to immobilized GST-Rho fusion proteins. In addition,
      brain Gbetagamma, but not transducin Gbetagamma, was able to inhibit GTPgammaS
      binding to GST-Rho in a concentration-dependent manner. GTPgammaS binding to GST
      Rac was also decreased by brain Gbetagamma whereas nucleotide binding to GST
      Cdc42 was not changed. We conclude that Gbetagamma dimers may participate in the
      process of membrane attachment and/or other regulations of Rho and Rac.

PMID- 8985148
TI  - Expression of active, human lysyl oxidase in Escherichia coli.
AB  - Lysyl oxidase (LO) is a copper amine oxidase of the extracellular matrix which
      initiates covalent cross-linking in collagens and elastin. Human LO was expressed
      in Escherichia coli. At 37 degrees C, large amounts of protein were obtained, but
      in the form of insoluble aggregates. Lowering the growth temperature, and
      reducing the amount of inducer, resulted in the production of soluble LO, which
      was active on a degrees [3H]lysine-labeled elastin substrate. LO was also
      targeted to the periplasm as a fusion protein with the pelb signal peptide. The
      periplasmic enzyme was soluble, active and inhibited by beta-aminopropionitrile.
      Production of the carbonyl co-factor is therefore not a limitation in the
      expression of active LO in bacteria.

PMID- 8985149
TI  - Slow-to-fast transitions in myosin expression of rat soleus muscle by phasic high
      frequency stimulation.
AB  - Denervated soleus muscles of euthyroid and hyperthyroid rats were exposed to
      phasic high-frequency stimulation for periods of up to 40 days and analysed for
      their myosin heavy chain (MHC) composition. Denervation alone induced appreciable
      amounts of the fast MHCIId/x and minute amounts of MHCIIb. However, the effects
      of phasic high-frequency stimulation exceeded by far those of denervation,
      leading to marked increases of these two isoforms, as well as to pronounced
      decreases in slow MHCI. In addition, the present study suggested a greater impact
      of neural activity on myosin expression than thyroid hormone.

PMID- 8985150
TI  - Interaction of 10Sa RNA with ribosomes in Escherichia coli.
AB  - 10Sa RNA is a bacterial small stable RNA, in which the 5'- and 3'-end sequences
      are folded into a tRNA-like structure. The RNA accepts alanine in vitro, and
      interacts with 70S ribosomes in the cells. In this study, we examined the
      ribosome-binding properties of Escherichia coli 10Sa RNA in vivo, and found that
      the aminoacylation ability of 10Sa RNA with alanine is necessary for the binding
      to 70S ribosomes. 10Sa RNA was also found to bind only to 70S monosomes and not
      to polysomes. Recently, E. coli 10Sa RNA was suggested to be used as mRNA for tag
      peptides, which were found to attach to the C-termini of truncated peptides
      synthesized in vivo. The present results are consistent with the 'trans
      translation' model, which has been proposed for tag-peptide synthesis.

PMID- 8985151
TI  - Purification of acid sphingomyelinase from human placenta: characterization and N
      terminal sequence.
AB  - Human placental acid sphingomyelinase (ASM) was purified by sequential
      chromatography on Con A-Sepharose, octyl-Sepharose and Matrex gel red A. Final
      purification to apparent homogeneity was achieved by immunoaffinity
      chromatography employing polyclonal anti-ASM antibodies. The antibodies also
      allowed specific detection of ASM by Western blotting at various stages of
      purification. The ASM activity was enriched about 110,000-fold over that of the
      crude extract, yielding an enzyme preparation with a specific activity of about 1
      mmol/h per mg protein in a detergent-containing assay system. Analysis of the
      final preparation by SDS-PAGE resulted in a single protein band with a molecular
      mass of approximately 75 kDa, which was reduced to approximately 60 kDa after
      complete deglycosylation. Microsequencing of the purified ASM revealed the N
      terminal amino acid sequence of the mature placental enzyme.

PMID- 8985152
TI  - Biosynthetically lipid-modified human scFv fragments from phage display libraries
      as targeting molecules for immunoliposomes.
AB  - A human anti-CD22 single chain (sc) Fv antibody fragment from a synthetic phage
      antibody display library was biosynthetically lipid-tagged by using Escherichia
      coli lipoprotein sequences. The purified anti-CD22 scFv lipoprotein was
      incorporated into liposomes by detergent dilution. Anti-CD22 immunoliposomes were
      shown to bind specifically in a dose- and time-dependent manner to CD22+ cell
      lines and CD22+ B-lymphocytes present in freshly isolated samples of blood
      mononuclear cells. The immunoliposomes were demonstrated to accumulate in
      intracellular compartments. Biosynthetically lipid-tagged human scFv antibody
      fragments isolated from phage display libraries may facilitate the construction
      of immunoliposomes with improved properties.

PMID- 8985153
TI  - Tight-binding inhibitory sequences against pp60(c-src) identified using a random
      15-amino-acid peptide library.
AB  - A bacteriophage peptide library containing a random 15-amino-acid insert was
      screened for identification of peptide sequence(s) that bind pp60(c-src).
      Sequencing the random insert from more than 100 virions indicated that more than
      60% of the phage virions that bound to this enzyme contained a GXXG sequence
      motif in which X was frequently a hydrophobic residue. The GXXG sequence was
      often repeated as GXXGXXG. Two nonameric peptides were synthesized to determine
      whether or not the peptide inhibits pp60(c-src) tyrosine kinase activity and the
      importance of the glycine residues within this sequence. The peptide containing
      glycine had a Ki of 24 microM, whereas replacing the glycines with proline
      increased the Ki value to 3.1 mM.

PMID- 8985154
TI  - Functional and possible physical association of scavenger receptor with
      cytoplasmic tyrosine kinase Lyn in monocytic THP-1-derived macrophages.
AB  - Acetyl LDL (modified low-density lipoprotein), which is thought to be taken up
      through scavenger receptor A (SR-A), rapidly induced the appearance of
      phosphotyrosine proteins in monocytic THP-1-derived macrophages in vitro. The two
      alternative forms of Lyn (p53 and p56) were found to be tyrosine-phosphorylated
      within 30 s after the stimulation with acetyl LDL. The catalytic activity of Lyn
      measured by an in vitro kinase assay had also increased in acetyl LDL-stimulated
      THP-1-derived macrophages. Furthermore, Lyn could be co-immunoprecipitated with
      SR-A from the cell lysate. These observations suggest a functional and possible
      physical association of SR-A with Lyn in THP-1-derived macrophages, and also
      imply a possible involvement of Lyn in SR-A signal transduction.

PMID- 8985155
TI  - A CK2 site is reversibly phosphorylated in the photosystem II subunit CP29.
AB  - Protein phosphorylation is a major mechanism in the regulation of protein
      function. In chloroplast thylakoids several photosystem II subunits, including
      the major antenna light-harvesting complex II and several core complex
      components, are reversibly phosphorylated depending on the redox state of the
      electron carriers. A previously unknown reversible phosphorylation event has
      recently been described on the CP29 subunit which leads to conformational changes
      and protection from cold stress (Bergantino, E., Dainese, P., Cerovic, Z. Sechi,
      S. and Bassi, R. (1995) J. Biol Chem. 270, 8474-8481). In this study, we have
      identified the phosphorylation site on the N-terminal, stroma-exposed domain,
      showing that it is located in a sequence not homologous to the other members of
      the Lhc family. The phosphorylated sequence is unique in chloroplast membranes
      since it meets the requirements for CK2 (casein kinase II) kinases. The
      possibility that this phosphorylation is involved in a signal transduction
      pathway is discussed.

PMID- 8985156
TI  - Complicated character of the M decay pH dependence in the D96N mutant is due to
      the two pathways of the M conversion.
AB  - At high ionic strength, the pH dependence of the M intermediate decay in a
      photocycle of the D96N mutant bacteriorhodopsin shows a complicated behavior
      which is found to be due to the coexistence of two pathways of the M conversion.
      The M decay which dominates at pH < 5 is coupled to the proton uptake from the
      cytoplasmic surface and proceeds probably through the N intermediate. This
      pathway is inhibited by glutaraldehyde, the potent inhibitor of M decay in the
      wild-type bacteriorhodopsin and of the azide-facilitated M decay in the D96N
      mutant. Another pathway of the M decay is predominant at pH > 5. This pathway is
      insensitive to glutaraldehyde and some other similar inhibitors (lutetium ions,
      sucrose and glycerol). On the other hand, it is sensitive to the pK changes of
      the group X (Glu-204) in the outward proton pathway. Possibly, the M decay
      through this pathway represents a reverse H+ transport process (the proton uptake
      from the external surface) and proceeds via the L intermediate.

PMID- 8985157
TI  - Kininogen binding protein p33/gC1qR is localized in the vesicular fraction of
      endothelial cells.
AB  - The endothelial protein p33/gC1qR is thought to mediate the assembly of
      components of the kinin-forming and complement-activating pathways on the surface
      of cardiovascular cells. FACS analysis of intact human umbilical vein endothelial
      cells using specific antibodies to p33 revealed a minor fluorescence on the cell
      surface whereas permeabilized cells showed a bright fluorescence indicative of an
      intracellular localization of p33. Immunostaining of fixed cells confirmed the
      predominant intracellular localization of p33. Fractionation studies demonstrated
      that the vesicular but not the membrane fraction of EA.hy926 cells is rich in
      p33. We conclude that externalization of p33 must precede its complex formation
      with target proteins on the endothelial cell surface.

PMID- 8985158
TI  - The heat shock factor and mitochondrial Hsp70 are necessary for survival of heat
      shock in Saccharomyces cerevisiae.
AB  - A heat shock recovery assay on solid medium (Nwaka et al. (1995) J. Biol. Chem.
      270, 10193-10198) as well as the classical cell counting method were used to
      investigate the function of some heat shock proteins in thermotolerance. We show
      that expression of intact heat shock factor protein (HSF), which regulates the
      stress induced expression of heat shock proteins (HSPs), is necessary for
      recovery from heat shock. A HSF1 mutant (hsf1-m3) which does not induce the
      expression of some heat shock proteins at heat stress (37-40 degrees C) is
      defective in recovery after heat shock at 50-52 degrees C compared to a
      corresponding wild-type strain in both stationary and exponentially growing
      cells. Using two temperature sensitive mutants of the mitochondrial Hsp70 (ssc1-2
      and ssc1-3) encoded by the SSC1 gene, we show that the ssc1-3 mutant, which has a
      mutation in the ATPase domain, is defective in recovery after heat shock in
      contrast to the ssc1-2 mutant, which has a mutation in the peptide binding
      domain. Different binding capacities for unfolded proteins are shown to be the
      molecular reason for the observed phenotypes. The thermotolerance defect of the
      hsf1-m3 and ssc1-3 mutants is demonstrated for both glucose and glycerol media.

PMID- 8985159
TI  - Septide and neurokinin A are high-affinity ligands on the NK-1 receptor: evidence
      from homologous versus heterologous binding analysis.
AB  - The three main tachykinins, substance P, neurokinin A (NKA), and neurokinin B,
      are believed to be selective ligands for respectively the NK-1, NK-2 and NK-3
      receptors. However, NKA also has actions which cannot be mediated through its
      normal NK-2 receptor and the synthetic peptide [pGlu6,Pro9]-Substance P9-11-
      called septide--is known to have tachykinin-like actions despite its apparent
      lack of binding to any known tachykinin receptor. In the cloned NK-1 receptor
      expressed in COS-7 cells NKA and septide as expected were poor competitors for
      radiolabeled substance P. However, by using radiolabeled NKA and septide
      directly, it was found that both peptides in homologous binding assays as well as
      in competition against each other in fact bound to the NK-1 receptor with high
      affinity: Kd values of 0.51 +/- 0.15 nM (NKA) and 0.55 +/- 0.03 nM (septide). It
      is concluded that NKA and septide are high-affinity ligands for the NK-1 receptor
      but that they are poor competitors for substance P, which in contrast competes
      very well for binding with both NKA and septide.

PMID- 8985161
TI  - Effect of the sugar chain of soluble recombinant CD59 on complement inhibitory
      activity.
AB  - A soluble recombinant CD59#77 (rCD59#77), consisting of 77 amino acids starting
      from the N terminus of membrane-bound CD59, was prepared using a gene expression
      system in CHO cells. The rCD59#77 preparation was composed of glycosylated and
      non-glycosylated forms (G and NG forms). Unexpectedly, NG form was 7 times more
      potent than G form in complement inhibitory activity. Postulating that sialic
      acids on G-form molecules make it difficult for rCD59#77 to access nascent
      membrane attack complexes on the cell surface, the sialic acids were removed by
      neuraminidase treatment. However, the inhibitory activity was not changed. Next,
      one of two putative N-glycosylation sites was mutated by substituting Gln18 for
      Asn18. The mutant, designated rCD59#77(N/Q), had no sugar moiety and was as
      active as the NG form of rCD59#77. These results suggest that the bulky sugar
      moiety at Asn18 is not necessary for the complement-inhibitory activity of rCD59
      and actually hampers that function.

PMID- 8985160
TI  - Lipopolysaccharide-binding protein mediates CD14-independent intercalation of
      lipopolysaccharide into phospholipid membranes.
AB  - Lipopolysaccharides (LPS, endotoxin) stimulate mononuclear cells to release
      cytokines which initiate endotoxic effects. Interaction of LPS at low
      concentrations with target cells is CD14-dependent whereas at high LPS
      concentrations it is CD14-independent. Here, we demonstrate by resonance energy
      transfer (RET) technique that nonspecific, CD14-independent intercalation of LPS
      into membrane systems can be mediated by lipopolysaccharide-binding protein
      (LBP). It is proposed that in this pathway, LBP breaks down LPS aggregates,
      transports the smaller units to and inserts them into the phospholipid cell
      matrix. We furthermore show that LBP also mediates the intercalation of other
      negatively charged amphiphilic molecules. We propose a model explaining CD14
      independent cell activation at high endotoxin concentrations.

PMID- 8985162
TI  - Involvement of extracellular calcium in phosphatidylserine exposure during
      apoptosis.
AB  - The appearance of phosphatidylserine (PS) on the outer surface of apoptotic cells
      is an important signal for their ingestion. In platelets, elevation of
      intracellular Ca2+ with thapsigargin can trigger large amounts of PS exposure
      within minutes. We detected PS exposure in U937 promonocytes and Jurkat T-cells
      after incubation with thapsigargin, but in only 10% of the cells, and it took up
      to 6 h to occur. Tumor necrosis factor and anti-Fas antibody rapidly trigger
      apoptosis in these cells, and chelation of extracellular Ca2+ with 5 mM EGTA
      inhibited PS exposure by 65% and 50%, respectively. Chelation of intracellular
      Ca2+ with BAPTA-AM had no effect. Other parameters of apoptosis, including cell
      blebbing, shrinkage, nuclear fragmentation, activation of the ICE-like proteases,
      and fodrin cleavage, were not inhibited by extracellular EGTA. We conclude that
      while an elevation of intracellular Ca2+ is an ineffective trigger of apoptosis
      in the cells investigated, extracellular Ca2+ is required for efficient PS
      exposure during apoptosis.

PMID- 8985163
TI  - Gene synthesis, high-level expression and assignment of backbone 15N and 13C
      resonances of soybean leghemoglobin.
AB  - A synthetic gene for apoleghemoglobin-a from soybean, optimized for expression in
      Escherichia coli has been designed and synthesized by a recursive polymerase
      chain reaction technique. The protein has been expressed with high efficiency and
      a purification protocol has been developed. The holoprotein is readily
      reconstituted by the addition of heme. 15N- and 15N,13C-labeled samples were
      produced and backbone 15N and 13C assignments were determined by 2D and 3D NMR
      spectroscopy. Comparison of the chemical shifts of 13C(alpha) and 13CO with
      random coil shifts revealed a pattern of secondary structure which correlates
      well with the one previously derived from homonuclear NMR data and low-resolution
      X-ray crystallography.

PMID- 8985164
TI  - Short photoperiod reduces leptin gene expression in white and brown adipose
      tissue of Djungarian hamsters.
AB  - Leptin gene expression in white (WAT) and brown adipose tissue (BAT) of the
      Djungarian hamster (Phodopus sungorus) was analyzed during seasonal
      acclimatization. Leptin gene expression in WAT was markedly reduced during
      winter, independent of changes in environmental temperature. Exposure to
      artificial short photoperiod also decreased leptin gene expression in WATas well
      as in BAT. Although specific leptin gene expression was lower in BAT, total depot
      expression was as high as in WAT depots, due to higher RNA content of BAT. Our
      results indicate that there is significant leptin synthesis in brown fat and that
      leptin might be involved in photoperiod mediated seasonal adaptations of mammals
      independent of food deprivation or overfeeding.

PMID- 8985165
TI  - cDNA cloning, sequence analysis and allergological characterization of Par j
      2.0101, a new major allergen of the Parietaria judaica pollen.
AB  - A clone (P2) coding for an allergen of Parietaria judaica (Pj) pollen has been
      isolated and sequenced from a cDNA library in lambda ZAP using a pool of 23 sera
      from Pj-allergic patients. The clone contained an insert of 622 nucleotides with
      an open reading frame of 133 amino acids (aa) and a putative signal peptide of 31
      aa giving a deduced mature processed protein of 102 aa with a molecular mass of
      11344 Da. The expressed recombinant protein, named rPar j 2.0101, was a major
      allergen since it reacted with IgE of 82% (23/28) of the sera of Pj-allergic
      subjects analyzed. It was shown to be a new allergen since (i) the amino acid
      sequence homology with the already reported recombinant allergen Par j 1.0101 was
      45% and (ii) there was no cross-inhibition between rPar j 2.0101 and rPar j
      1.0101. In addition, rPar j 2.0101 inhibited 35% of the specific IgE for 10-14
      kDa native allergens and preincubation of sera from Pj-allergic patients with
      both rPar j 2.0101 and rPar j 1.0101 fully abolished the IgE recognition of the
      10-14 kDa native allergen region, suggesting that these two allergens contributed
      to the region.

PMID- 8985166
TI  - Identification by bacterial expression and functional reconstitution of the yeast
      genomic sequence encoding the mitochondrial dicarboxylate carrier protein.
AB  - The inner membranes of mitochondria contain a family of transport proteins of
      related sequence and structure. The DNA sequence of the genome of Saccharomyces
      cerevisiae encodes at least 35 members of this family. Three of them can be
      recognised as known isoforms of the ADP-ATP translocase and two others as the
      phosphate and citrate carriers. The transport functions of the remainder cannot
      be identified with certainty. One of them, encoded on yeast chromosome xii, shows
      a fairly close sequence relationship to the known sequence of the bovine
      mitochondrial oxoglutarate-malate carrier. The yeast protein has been obtained by
      over-expression in Escherichia coli, reconstituted into phospholipid vesicles and
      shown to have transport properties characteristic of the mitochondrial carrier
      for dicarboxylate ions, such as malate, and also phosphate, previously
      biochemically characterised, but not sequenced, from both mammalian and yeast
      mitochondria. This is the first example of the biochemical identification of an
      unknown membrane protein encoded in the yeast genome since the completion of the
      genomic sequence.

PMID- 8985167
TI  - Effect of side groups on the action of beta-xylosidase from Trichoderma reesei
      against substituted xylo-oligosaccharides.
AB  - The action of beta-xylosidase from Trichoderma reesei against different
      substituted xylo-oligosaccharides was studied. The enzyme cleaved off all
      unsubstituted xylose units from the non-reducing end of 1,2-linked uronic acid
      substituted xylo-oligosaccharides. Surprisingly, an L-arabinofuranosyl group
      linked alpha-1,3 to the xylopyranosyl ring was found to protect the beta-1,4
      xylosidic linkage before the substituted xylose unit from being cleaved by the
      beta-xylosidase. Most probably the 1,3-linked substituent sterically hinders the
      hydrolysis. According to the results of the present work, beta-xylosidase of T.
      reesei is not able to remove all unsubstituted xylose units from the non-reducing
      end of substituted xylo-oligosaccharides, as had been believed previously.

PMID- 8985168
TI  - Assembly of a cytoplasmic membrane protein in Escherichia coli is dependent on
      the signal recognition particle.
AB  - Targeting of the cytoplasmic membrane protein leader peptidase (Lep) and a Lep
      mutant (Lep-inv) that inserts with an inverted topology compared to the wild-type
      protein was studied in Escherichia coli strains that are conditional for the
      expression of either Ffh or 4.5S RNA, the two components of the E. coli SRP.
      Depletion of either component strongly affected the insertion of both Lep and Lep
      inv into the cytoplasmic membrane. This indicates that SRP is required for the
      assembly of cytoplasmic membrane proteins in E. coli.

PMID- 8985169
TI  - Long-chain fatty acids suppress the induction of urea cycle enzyme genes by
      glucocorticoid action.
AB  - In order to test the possibility that free fatty acids are the mediator of the
      abnormal expression of urea cycle enzyme genes in carnitine-deficient juvenile
      visceral steatosis (JVS) mice, the effects of fatty acids on urea cycle enzyme,
      carbamoylphosphate synthetase (CPS) and argininosuccinate synthetase (ASS), mRNA
      levels were examined in rat primary cultured hepatocytes. Addition of a synthetic
      glucocorticoid hormone, dexamethasone, caused increases in CPS and ASS mRNAs.
      Further addition of oleic acid suppressed the induction of CPS and ASS mRNAs by
      dexamethasone. In contrast, the phosphoenolpyruvate carboxykinase (PEPCK) mRNA
      level induced by dexamethasone was enhanced in the presence of oleic acid. The
      effects were reversed on further addition of carnitine. The mRNA levels of these
      enzymes induced by dibutyryl cAMP were not affected by the addition of oleic
      acid. A study of the specificity of fatty acids revealed that long-chain fatty
      acids of more than 16 carbons chain length had a suppressive effect on the CPS
      mRNA level induced by dexamethasone and that the presence of double bonds
      enhanced the effect. The changes in gene expression of CPS, ASS and PEPCK caused
      by the fatty acids in the cultured hepatocytes were very similar to those
      observed in the liver of JVS mice. The AP-1 DNA binding activity in the presence
      of dexamethasone was slightly enhanced by the addition of oleic acid. These
      results suggest that the long-chain fatty acids not metabolized in JVS mice are
      mediators of the abnormal gene expression in the liver which results in
      hyperammonemia.

PMID- 8985170
TI  - Mutations in the amino-terminal domain of the human poly(ADP-ribose) polymerase
      that affect its catalytic activity but not its DNA binding capacity.
AB  - Poly-ADP ribosylation of nuclear proteins is activated when poly(ADP-ribose)
      polymerase (PARP), a nuclear zinc-finger enzyme, binds to single-strand DNA
      breaks. To understand how the signal emerging from its DNA-binding domain (DBD)
      bound to such breaks is transduced to its catalytic domain, the structure
      function relationship of the DBD was investigated. We have used mutagenesis by
      the polymerase chain reaction (PCR) to generate a random library of PARP mutants.
      In this work, we describe the identification of catalytically inactive mutants
      bearing single point mutations, located outside the two zinc fingers in the DBD,
      that have conserved their full capacity to bind DNA. The results obtained
      demonstrate that the DNA-dependent activation of PARP requires not only a
      capacity to bind DNA but also a number of crucial residues to maintain a
      conformation of the domain necessary to transfer an 'activation signal' to the
      catalytic domain.

PMID- 8985171
TI  - The involvement of the Saccharomyces cerevisiae multidrug resistance transporters
      Pdr5p and Snq2p in cation resistance.
AB  - The ATP-binding cassette superfamily proteins Pdr5p and Snq2p of Saccharomyces
      cerevisiae are implicated in multidrug resistance. Here, we show that these
      transporters are also involved in cation resistance. Null mutants of PDR5 and
      SNQ2 genes exhibit increased sensitivity to NaCl, LiCl and MnCl2. The mutant
      cells grown in the presence of high concentrations of these metal salts contain
      higher levels of the metals than wild-type cells. The expression of PDR5 and SNQ2
      is induced by the metal salts. These results provide evidence that the yeast drug
      transporters contribute to cation resistance by regulating cellular cation
      homeostasis under ionic stress conditions.

PMID- 8985172
TI  - Effect of substance P on cytokine production by human astrocytic cells and blood
      mononuclear cells: characterization of novel tachykinin receptor antagonists.
AB  - Substance P (SP) has been reported to induce inflammatory cytokine production in
      human neuroglial cells and peripheral lymphoid cells as well. In order to
      evaluate the potency of novel non-peptide antagonists of the tachykinin receptors
      as inhibitors of SP-induced cytokines, we used the astrocytoma cell line U373MG
      and blood mononuclear cells as models of central and peripheral SP-target cells,
      respectively. In the first part of this study, we showed that SR 140333, an NK1
      tachykinin receptor antagonist, was able to inhibit strongly the SP-induced
      production of interleukin (IL)-6 and IL-8 in the astrocytoma cell line. The
      antagonistic activity of SR 140333 toward SP-induced cytokine production was
      specific and could not be attributed to a general anti-cytokine effect, since
      cytokine release induced by another inflammatory protein such as IL-1beta was not
      blocked by this compound. In addition, NK2 and NK3 agonist neuropeptides were at
      least 1000-fold less effective than SP, while SR 48968 and SR 142801 which are
      selective NK2 and NK3 receptor antagonists, respectively, displayed a 2.5-3
      orders of magnitude lower inhibitory potency than SR 140333. All these data
      indicated that SR 140333 blocked SP-induced cytokine production in U373MG
      astrocytic cells via a specific NK1 receptor-mediated process. Since SP has also
      been described to trigger peripheral blood mononuclear cells (PBMNC) or monocytes
      to release inflammatory cytokines, we attempted, in the second part of this
      study, to evaluate the potential antagonistic effect of our compounds on these
      cells. Experiments on human PBMNC from different donors were carried out to
      determine first their pattern of cytokine production upon SP stimulation.
      Surprisingly, we noticed that SP at concentrations ranging from 0.1 to 1000 nM
      was unable to stimulate the release of any inflammatory cytokine tested. This
      raises the question of the specificity of the reported in vitro effects of SP on
      cytokine production by human peripheral immune cells.

PMID- 8985173
TI  - The SH3 domain of the tight junction protein ZO-1 binds to a serine protein
      kinase that phosphorylates a region C-terminal to this domain.
AB  - ZO-1 is a tight junction phosphoprotein partially homologous to a tumor
      suppressor in Drosophila. The homologous region contains an SH3 domain with an
      unidentified function. Using fusion proteins containing the SH3 domain and
      various N- and C-terminal sequences, we tested for association of a kinase with
      this protein domain in extracts of MDCK cells. We show that the SH3 domain of ZO
      1 binds a serine protein kinase that phosphorylates a region immediately C
      terminal to the SH3 domain. This kinase associates specifically with the SH3
      domain of ZO-1 and appears to be also associated with junctional complexes
      extracted from MDCK cells.

PMID- 8985174
TI  - Molecular basis for the substrate specificity of protein kinase B; comparison
      with MAPKAP kinase-1 and p70 S6 kinase.
AB  - The substrate specificity of protein kinase-B alpha (PKBalpha, also known as RAC
      kinase or Akt) was investigated using synthetic peptide substrates related to the
      sequence surrounding the phosphorylation site on glycogen synthase kinase-3
      (GSK3). The minimum sequence motif required for efficient phosphorylation was Arg
      Xaa-Arg-Yaa-Zaa-Ser/Thr-Hyd, where Xaa is any amino acid, Yaa and Zaa are small
      residues other than glycine and Hyd is a bulky hydrophobic residue (Phe, Leu).
      The most effective substrate, Arg-Pro-Arg-Thr-Ser-Ser-Phe, was phosphorylated
      with a Km of 5 microM and Vmax of 260 U/mg. PKBalpha phosphorylated histone H2B
      (Km 5 microM, Vmax 68 U/mg) specifically at Ser-36 which also lies in an Arg-Xaa
      Arg-Xaa-Xaa-Ser-Hyd motif. The peptide Arg-Pro-Arg-Ala-Ala-Thr-Phe may be a
      relatively specific substrate for PKBalpha because, unlike other substrates, it
      is not phosphorylated by p70 S6 kinase or MAP kinase activated protein (MAPKAP)
      kinase-1.

PMID- 8985175
TI  - Amino acid sequence of a novel protein phosphatase 1 binding protein (R5) which
      is related to the liver- and muscle-specific glycogen binding subunits of protein
      phosphatase 1.
AB  - A full-length cDNA encoding a novel human protein phosphatase 1 (PP1) binding
      subunit of molecular mass 36 kDa, termed PPP1R5, was sequenced. PPP1R5 shows 42%
      identity to the glycogen binding subunit (G(L)) of PP1 from rat liver and 28%
      identity to the N-terminal region of the glycogen binding subunit (G(M)) of PP1
      from human skeletal muscle. Like G(L), PPP1R5 modulates the specificity of PP1,
      but it differs from G(L) in being present in a wide variety of tissues, besides
      liver. The amino acid sequence and properties of PPP1R5 indicate that it is not
      subject to the same modes of covalent and allosteric regulation by hormones as
      are G(M) and G(L).

PMID- 8985176
TI  - RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer
      like paired helical filaments.
AB  - The microtubule-associated protein tau is the main component of the paired
      helical filaments (PHFs) of Alzheimer's disease, the most common senile dementia.
      To understand the origin of tau's abnormal assembly we have studied the influence
      of other cytosolic components. Here we report that PHF assembly is strongly
      enhanced by RNA. The RNA-induced assembly of PHFs is dependent on the formation
      of intermolecular disulfide bridges involving Cys322 in the third repeat of tau,
      and it includes the dimerization of tau as an early intermediate. Three-repeat
      constructs polymerize most efficiently, two repeat constructs are the minimum
      number required for assembly, and even all six full-length isoforms of tau can be
      induced to form PHFs by RNA.

PMID- 8985177
TI  - From screens to genes: prospects for insertional mutagenesis in zebrafish.

PMID- 8985178
TI  - Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC
      dependent degradation of the anaphase inhibitor Pds1p.
AB  - Anaphase initiation has been postulated to be controlled through the ubiquitin
      dependent proteolysis of an unknown inhibitor. This process involves the anaphase
      promoting complex (APC), a specific ubiquitin ligase that has been shown to be
      involved in mitotic cyclin degradation. Previous studies demonstrated that in
      Saccharomyces cerevisiae, Pds1 protein is an anaphase inhibitor and suggested
      that it may be an APC target. Here we show that in yeast cells and in mitotic
      Xenopus extracts Pds1p is degraded in an APC-dependent manner. In addition, Pds1p
      is directly ubiquitinated by the Xenopus APC. In budding yeast Pds1p is degraded
      at the time of anaphase initiation and nondegradable derivatives of Pds1p inhibit
      the onset of anaphase. We conclude that Pds1p is an anaphase inhibitor whose APC
      dependent degradation is required for the initiation of anaphase.

PMID- 8985179
TI  - Est1 has the properties of a single-stranded telomere end-binding protein.
AB  - In Saccharomyces cerevisiae, deletion of the EST1 gene results in phenotypes
      identical to those displayed by a deletion of a known component of telomerase
      (the yeast telomerase RNA), arguing that EST1 is also critical for telomerase
      function. In this study, we show that the Estl protein binds to yeast G-rich
      telomeric oligonucleotides in vitro. Binding is specific for single-stranded
      substrates and requires a free 3' terminus, consistent with the properties
      expected for a protein bound to the 3' single-stranded G-rich extension present
      at the telomere. Assessment of the in vivo function of this single-stranded DNA
      binding protein has shown that EST1 acts in the same pathway of telomere
      replication as the TLC1 telomerase RNA, by several different genetic criteria:
      est1 tlc1 double mutant strains show no enhancement of phenotype relative to
      either single mutant strain, and EST1 dominant mutations have an effect on
      telomeric silencing similar to that displayed by TLC1 previously. We propose that
      Est1 is a telomere end-binding protein that is required to mediate recognition of
      the end of the chromosome by telomerase.

PMID- 8985180
TI  - Glucose regulates protein interactions within the yeast SNF1 protein kinase
      complex.
AB  - The SNF1 protein kinase is broadly conserved in eukaryotes and has been
      implicated in responses to environmental and nutritional stress. In yeast, the
      SNF1 kinase has a central role in the response to glucose starvation. SNF1 is
      associated with its activating subunit, SNF4, and other proteins in complexes.
      Using the two-hybrid system, we show that interaction between SNF1 and SNF4 is
      strongly regulated by the glucose signal. Moreover, this interaction is
      appropriately affected by mutations in regulators, including protein phosphatase
      1. We show that SNF4 binds to the SNF1 regulatory domain in low glucose, whereas
      in high glucose the regulatory domain binds to the kinase domain of SNF1 itself.
      Genetic analysis further suggests that the SNF1 regulatory domain autoinhibits
      the kinase activity and that in low glucose SNF4 antagonizes this inhibition.
      Finally, these interactions have been conserved from yeast to plants, indicating
      that homologs of the SNF1 kinase complex respond to regulatory signals by
      analogous mechanisms.

PMID- 8985181
TI  - The segment polarity gene porcupine encodes a putative multitransmembrane protein
      involved in Wingless processing.
AB  - The Wnt protein Wingless (Wg) functions as a signal in patterning of both the
      Drosophila embryo and imaginal discs. Lack of porcupine (porc) activity is
      associated with mutant phenotypes similar to those of wg mutations. In porc
      mutant embryos, Wg protein is confined to the cells that produce it, suggesting
      that Porc plays a role in processing or secretion of Wg. porc encodes a novel
      transmembrane protein that appears to be concentrated at the endoplasmic
      reticulum. We present both genetic and in vitro evidence demonstrating that porc
      is involved specifically in the processing of Wg. We identified a human sequence
      related to Porc suggesting the existence of a family of proteins involved in
      processing of Wnts.

PMID- 8985182
TI  - Single factors direct the differentiation of stem cells from the fetal and adult
      central nervous system.
AB  - Identifying the signals that regulate stem cell differentiation is fundamental to
      understanding cellular diversity in the brain. In this paper we identify factors
      that act in an instructive fashion to direct the differentiation of
      multipotential stem cells derived from the embryonic central nervous system
      (CNS). CNS stem cell clones differentiate to multiple fates: neurons, astrocytes,
      and oligodendrocytes. The differentiation of cells in a clone is influenced by
      extracellular signals: Platelet-derived growth factor (PDGF-AA, -AB, and -BB)
      supports neuronal differentiation. In contrast, ciliary neurotrophic factor and
      thyroid hormone T3 act instructively on stem cells to generate clones of
      astrocytes and oligodendrocytes, respectively. Adult stem cells had remarkably
      similar responses to these growth factors. These results support a simple model
      in which transient exposure to extrinsic factors acting through known pathways
      initiates fate decisions by multipotential CNS stem cells.

PMID- 8985184
TI  - Characterization of human lysosomal neuraminidase defines the molecular basis of
      the metabolic storage disorder sialidosis.
AB  - Neuraminidases (sialidases) have an essential role in the removal of terminal
      sialic acid residues from sialoglycoconjugates and are distributed widely in
      nature. The human lysosomal enzyme occurs in complex with beta-galactosidase and
      protective protein/cathepsin A (PPCA), and is deficient in two genetic disorders:
      sialidosis, caused by a structural defect in the neuraminidase gene, and
      galactosialidosis, in which the loss of neuraminidase activity is secondary to a
      deficiency of PPCA. We identified a full-length cDNA clone in the dbEST data
      base, of which the predicted amino acid sequence has extensive homology to other
      mammalian and bacterial neuraminidases, including the F(Y)RIP domain and "Asp
      boxes." In situ hybridization localized the human neuraminidase gene to
      chromosome band 6p21, a region known to contain the HLA locus. Transient
      expression of the cDNA in deficient human fibroblasts showed that the enzyme is
      compartmentalized in lysosomes and restored neuraminidase activity in a PPCA
      dependent manner. The authenticity of the cDNA was verified by the identification
      of three independent mutations in the open reading frame of the mRNA from
      clinically distinct sialidosis patients. Coexpression of the mutant cDNAs with
      PPCA failed to generate neuraminidase activity, confirming the inactivating
      effect of the mutations. These results establish the molecular basis of
      sialidosis in these patients, and clearly identify the cDNA-encoded protein as
      lysosomal neuraminidase.

PMID- 8985183
TI  - Insertional mutagenesis in zebrafish identifies two novel genes, pescadillo and
      dead eye, essential for embryonic development.
AB  - Recently our laboratory described an efficient method for generating retroviral
      provirus insertions in the zebrafish germ line, and we showed that provirus
      insertions induce embryonic mutations at a frequency of roughly one mutant per 70
      insertions. To date we have isolated four insertional mutants and, using the
      proviruses as a molecular tag, have cloned the genes disrupted in three of them.
      The proviruses in all three mutants lie within or just 5' of the first coding
      exon, point in the opposite transcriptional orientation from the gene, and
      disrupt transcription. Here we present a molecular characterization of two genes
      identified by this method and describe the associated mutant phenotypes. The
      pescadillo (pes) gene is predicted to encode a protein of 582 amino acids with no
      recognizable functional motifs, which is highly conserved from yeast to humans.
      pes mRNA is expressed widely and dynamically during the first 3 days of
      embryogenesis. Prominent sites of expression are the eyes and optic tectum on day
      1, the fin buds, liver primordium, and gut on day 2, and the branchial arches on
      day 3. Beginning at day 3 of embryogenesis, pes mutant embryos exhibit small
      eyes, a reduced brain and visceral skeleton, shortened fins, and a lack of
      expansion of the liver and gut, and then die on the sixth day of development. The
      dead eye (dye) gene encodes a protein of 820 amino acids that is homologous to
      genes of unknown function in human, mouse, and Xenopus, and that has weak
      homology with the yeast NIC96 (nucleoporin-interacting component) gene. dye
      mutants can be recognized on day 2 of embryogenesis by the presence of necrotic
      cells in the tectum and eyes. dye mutants die on day 5 of development. These
      results demonstrate the power of insertional mutagenesis in zebrafish for rapidly
      finding and characterizing novel genes essential for embryonic development. Using
      our current methodology, we estimate that our laboratory could screen
      approximately 25,000 insertions in 2-3 years, identifying perhaps 250-350
      embryonic lethal genes. Assuming that all genes are accessible to proviral
      insertion, the wider application of this approach could lead to the rapid
      identification of the majority of genes that are required for embryonic
      development of this vertebrate.

PMID- 8985185
TI  - SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates
      in the assembly of outer membrane porins.
AB  - Little is known about either the process of periplasmic protein folding or how
      information concerning the folding state in this compartment is communicated. We
      present evidence that SurA, a periplasmic protein with peptidyl-prolyl isomerase
      activity, is involved in the maturation and assembly of LamB. LamB is a trimeric
      outer membrane porin for maltodextrins as well as the bacteriophage lambda
      receptor in Escherichia coli. We demonstrate that SurA is involved in the
      conversion of unfolded monomers into a newly identified intermediate in LamB
      assembly, which behaves as a folded monomer. The absence of SurA blocks the
      assembly pathway and leads to accumulation of species prior to the folded
      monomer. These species also accumulate when the stress sigma factor sigmaE is
      induced by LamB overexpression. We suggest that accumulation of species prior to
      the generation of folded monomer is a stress signal sensed by sigmaE.

PMID- 8985186
TI  - Segmentation and specification of the Drosophila mesoderm.
AB  - Patterning of the developing mesoderm establishes primordia of the visceral,
      somatic, and cardiac tissues at defined anteroposterior and dorsoventral
      positions in each segment. Here we examine the mechanisms that locate and
      determine these primordia. We focus on the regulation of two mesodermal genes:
      bagpipe (bap), which defines the anlagen of the visceral musculature of the
      midgut, and serpent (srp), which marks the anlagen of the fat body. These two
      genes are activated in specific groups of mesodermal cells in the anterior
      portions of each parasegment. Other genes mark the anlagen of the cardiac and
      somatic mesoderm and these are expressed mainly in cells derived from posterior
      portions of each parasegment. Thus the parasegments appear to be subdivided, at
      least with respect to these genes, a subdivision that depends on pair-rule genes
      such as even-skipped (eve). We show with genetic mosaics that eve acts
      autonomously within the mesoderm. We also show that hedgehog (hh) and wingless
      (wg) mediate pair-rule gene functions in the mesoderm, probably partly by acting
      within the mesoderm and partly by inductive signaling from the ectoderm. hh is
      required for the normal activation of bap and srp in anterior portions of each
      parasegment, whereas wg is required to suppress bap and srp expression in
      posterior portions. Hence, hh and wg play opposing roles in mesoderm
      segmentation.

PMID- 8985187
TI  - The Fab-7 element of the bithorax complex attenuates enhancer-promoter
      interactions in the Drosophila embryo.
AB  - Enhancers integrate positive and negative regulatory information to direct
      localized patterns of gene expression in the Drosophila embryo. Here we present
      evidence for the occurrence of cis regulatory elements that control the levels of
      gene expression by modulating enhancer-promoter interactions. For this purpose we
      have investigated the Drosophila bithorax complex (BX-C) because genetic studies
      suggest that the BX-C contains as much as 300 kb of cis regulatory information. A
      specialized DNA element, Fab-7, has been proposed to function as a boundary
      element that separates the iab-6 and iab-7 cis regulatory regions within the Abd
      B domain of the BX-C. A 1.2-kb Fab-7 DNA fragment was placed between divergently
      transcribed white and lacZ test promoters and challenged with several defined
      enhancers expressed in the early embryo. These studies suggest that Fab-7
      functions as an attenuator, which weakens gene expression by reducing enhancer
      promoter interactions. Fab-7 selectively blocks distal enhancers in an
      orientation-independent fashion, and can function when located far from either
      the distal enhancer or target promoter. Fab-7 may be related to insulator DNAs,
      which flank genetic loci and functionally isolate neighboring genes. We propose
      that specialized DNA elements, such as the Fab-7 attenuator, might play a general
      role in controlling the levels of gene expression by modulating enhancer-promoter
      interactions.

PMID- 8985188
TI  - Fab-7 functions as a chromatin domain boundary to ensure proper segment
      specification by the Drosophila bithorax complex.
AB  - Fab-7 deletions in the bithorax complex have a novel gain-of-function phenotype,
      typically transforming parasegment 11 (PS11) into PS12 identity. Genetic analysis
      indicates that removal of the Fab-7 element results in the fusion of the iab-6
      (PS11) and iab-7 (PS12) cis-regulatory domains into a single regulatory domain
      that inappropriately regulates Abdominal-B in PS11. This has led to the
      hypothesis that Fab-7 is a chromatin domain boundary that normally functions to
      ensure the autonomous activity of the iab-6 and iab-7 cis-regulatory domains. We
      use several different enhancer blocking assays to demonstrate that Fab-7 has the
      insulating properties expected of a domain boundary. We define a minimal fragment
      of Fab-7 sufficient for enhancer blocking, and demonstrate that it is completely
      distinct from an adjacent Polycomb-dependent silencer. We compare Fab-7 to the
      su(Hw) insulator element, and show that Fab-7 enhancer blocking activity is
      intermediate between that of five and twelve reiterated binding sites for the
      Su(Hw) protein. These results support the model that Fab-7 functions as a domain
      boundary within the context of the bithorax complex, making Fab-7 one of the
      first boundary elements that is known to have an essential function in vivo.

PMID- 8985189
TI  - Influenza vaccination of health care workers in long-term-care hospitals reduces
      the mortality of elderly patients.
AB  - Vaccination of health care workers (HCWs) is recommended as a strategy for
      preventing influenza in elderly patients in long-term care. However, there have
      been no controlled studies to show whether this approach is effective. During the
      winter of 1994-1995, 1059 patients in 12 geriatric medical long-term-care sites,
      randomized for vaccination of HCWs, were studied. In hospitals where HCWs were
      offered vaccination, 653 (61%) of 1078 were vaccinated. Vaccination of HCWs was
      associated with reductions in total patient mortality from 17% to 10% (odds ratio
      [OR], 0.56; 95% confidence interval [CI], 0.40-0.80) and in influenza-like
      illness (OR, 0.57; 95% CI, 0.34-0.94). Vaccination of patients was not associated
      with significant effects on mortality (OR, 1.15; 95% CI, 0.81-1.64). Results of
      this study support recommendations for vaccination against influenza of HCWs in
      long-term geriatric care. Vaccination of frail elderly long-term-care patients
      may not give clinically worthwhile benefits.

PMID- 8985190
TI  - Transmission of swine influenza virus to humans after exposure to experimentally
      infected pigs.
AB  - Two people developed symptoms of influenza 36 h after collecting nasal swabs from
      pigs experimentally infected with A/Sw/IN/1726/88 (Sw/IN). Pharyngeal swabs from
      these persons tested positive for influenza virus RNA 8 days after infection.
      Analysis of hemi-nested polymerase chain reaction (PCR) products indicated that
      the hemagglutinin (HA) segments of the isolates were genetically related to the
      HA of Sw/IN. Four influenza A virus isolates (A/WI/4754/94, A/WI/4756/94,
      A/WI/4758/94, A/WI/4760/94) were recovered from a 39-year-old man and 2
      (A/WI/4755/94, A/WI/4757/94) from a 31-year-old woman. The HAs of the isolates
      were antigenically indistinguishable from the virus used to infect the pigs.
      Sequence analysis of the HA genes indicated they were 99.7% identical to the HA
      of the virus used in the experiment. Multisegment reverse transcription-PCR
      proved that all of the segments originated from Sw/IN, demonstrating that
      transmission of swine H1N1 viruses to humans occurs directly and readily, despite
      Animal Biosafety Level 3 containment practices used for these experiments.

PMID- 8985191
TI  - A genetically inactivated herpes simplex virus type 2 (HSV-2) vaccine provides
      effective protection against primary and recurrent HSV-2 disease.
AB  - A glycoprotein H (gH)-deleted herpes simplex virus type 2 (HSV-2) was evaluated
      as a vaccine for the prevention of HSV-induced disease. This virus, which we term
      a DISC (disabled infectious single cycle) virus, can only complete one
      replication cycle in normal cells and should thus be safe yet still able to
      stimulate broad humoral and cell-mediated antiviral immune responses. A gH
      deleted HSV-2 virus that has been tested as a vaccine in the guinea pig model of
      recurrent HSV-2 infection was constructed. Animals vaccinated with DISC HSV-2
      showed complete protection against primary HSV-2-induced disease, even when
      challenged 6 months after vaccination. In addition, the animals were almost
      completely protected against recurrent disease. Even at low vaccination doses,
      there was a high degree of protection against primary disease. A reduction in
      recurrent disease symptoms was also observed following therapeutic vaccination of
      animals already infected with wild type HSV-2.

PMID- 8985192
TI  - Patients infected with the same hepatitis C virus strain display different
      kinetics of the isolate-specific antibody response.
AB  - The antibody response to the hypervariable region of the E2 protein (HVR1) of
      hepatitis C virus (HCV) was studied in 5 patients who were infected by a common
      virus strain during an outbreak in a hemodialysis unit. Two patients resolved the
      infection, while 3 developed chronic HCV infection. For studying the antibody
      response to HVR1 during the early phase of infection, a Western blot assay using
      recombinant phage displaying HVR1 was developed. The 2 patients with resolving
      infection had a more rapid antibody response to HVR1 than did the patients
      developing chronic infection. Anti-HVR1 antibodies were repeatedly absent in 1 of
      the chronically infected patients. Antibodies to recombinant E2 protein occurred
      later than the anti-HVR1 antibodies and did not correlate with resolution of the
      infection. Thus, the present results suggest that early appearance of antibodies
      to the HVR1 may predict clearance of HCV infection.

PMID- 8985193
TI  - Increase in CD23+ B cells in infants with bronchiolitis is accompanied by
      appearance of IgE and IgG4 antibodies specific for respiratory syncytial virus.
AB  - Infection with respiratory syncytial virus (RSV) may induce asthma-like symptoms
      and RSV-specific IgE in infected infants as a result of Th2-like response to RSV.
      The effect of RSV infection on the expression of B cell antigens CD21 and CD23,
      putative participants in Th2 responses, was investigated. Samples from
      bronchiolitic infants (n = 19) were tested by three-color immunofluorescence flow
      cytometry during the acute phase of infection and 4-6 weeks later. In 6 of 10 RSV
      positive infants, the percentage of CD23+ B cells was higher than in 9 RSV
      negative children and in controls. Both CD21+ and CD21- B cells exhibited a
      higher percentage of CD23. The group with increased expression of CD23 antigen
      had RSV-specific IgE and IgG4 antibodies. These findings corroborate the
      hypothesis that RSV could provoke a Th2-type response, but the relationship
      between CD23 antigen and RSV infection must be determined.

PMID- 8985194
TI  - Antibody and antibody-dependent cellular cytotoxicity responses against the BamHI
      A rightward open-reading frame-1 protein of Epstein-Barr virus (EBV) in EBV
      associated disorders.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) is an important antiviral
      effector mechanism. ADCC to the protein encoded by the Epstein-Barr virus (EBV)
      BamHI A rightward open-reading frame-1 (BARF1) was studied by transducing Raji-tk
      cells with the BARF1 gene using a retroviral expression vector. The transduced
      Raji cells expressed BARF1 on the cell surface, as determined by flow cytometry.
      Sera from chronic and acute infectious mononucleosis and nasopharyngeal carcinoma
      patients were found to contain antibodies that react with the BARF1 protein. When
      BARF1-expressing Raji cells were used as targets for ADCC, sera from several
      nasopharyngeal carcinoma patients demonstrated significant ADCC reactivity,
      whereas sera from healthy EBV-seronegative and -seropositive persons lacked such
      reactivity. BARF1-specific ADCC activity could be competitively inhibited with
      recombinant BARF1 protein. The level of anti-BARF1 antibody activity in sera of
      patients with EBV-associated diseases suggests that the BARF1 protein may serve
      as a target on EBV-infected cells for ADCC.

PMID- 8985195
TI  - Cytokine pattern in relation to disease progression in human immunodeficiency
      virus-infected children.
AB  - Cytokine mRNA expression and stimulus-induced cytokines were examined in
      peripheral blood mononuclear cells in 62 human immunodeficiency virus (HIV)
      infected children and uninfected controls. Compared with that in controls,
      constitutive mRNA expression in patients was increased for tumor necrosis factor
      (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-10 and decreased for IL
      12; it was undetectable for IL-2 and IL-4 in both patients and controls. Stimulus
      induced secretion of TNF-alpha, IFN-gamma, IL-12, and IL-4 was less than that in
      controls; IL-10 secretion was similar. There was no increase in stimulus-induced
      or constitutive IL-4 or IL-10 in children with severe immunologic deficit
      compared with controls. A higher stimulus-induced IL-10 secretion and a lower
      constitutive TNF-alpha mRNA were associated with a slower rate of disease
      progression, and TNF-alpha mRNA expression correlated with lower plasma HIV RNA.
      Thus, constitutive cytokine mRNA expression differs from stimulus-induced
      cytokine responses. The dominant defect in HIV-infected children appears to be
      one of reduced type 1 cytokines, predominantly IL-2.

PMID- 8985197
TI  - Vertical transmission of human immunodeficiency virus type 1: seroreactivity by
      maternal antibodies to the carboxy region of the gp41 envelope glycoprotein.
AB  - Maternal antibodies against the envelope glycoprotein of human immunodeficiency
      virus type 1 (HIV-1) have previously been suggested to be important in
      influencing the rate of vertical transmission. In this study, serum antibody
      responses in mothers who did or did not transmit HIV-1 infection to their
      children were measured against the carboxy region of the transmembrane envelope
      glycoprotein gp41. Results indicate significantly higher binding reactivity of
      nontransmitter mothers compared with transmitters to three peptides spanning
      amino acids 771-810 and 841-856. In addition, high neutralization titers in
      maternal sera against HIV-1(MN) were associated with a nontransmission status.
      This is the initial report demonstrating a correlation between maternal antibody
      binding to epitopes within the carboxy region of gp41 envelope glycoprotein and
      lack of vertical transmission. Immunodetection that identifies antibodies to
      these regions in gp41 could therefore be considered a strategy to assess the risk
      of vertical transmission of HIV-1.

PMID- 8985196
TI  - Genital shedding of human immunodeficiency virus type 1 DNA during pregnancy:
      association with immunosuppression, abnormal cervical or vaginal discharge, and
      severe vitamin A deficiency.
AB  - The presence of human immunodeficiency virus type 1 (HIV-1) in genital secretions
      may be a determinant of vertical HIV-1 transmission. Cervical and vaginal
      secretions from HIV-1-seropositive pregnant women were evaluated to determine
      prevalence and correlates of HIV-1-infected cells in the genital tract. HIV-1 DNA
      was detected by polymerase chain reaction in 32% of 212 cervical and 10% of 215
      vaginal specimens. Presence of HIV-1 DNA in the cervix was associated with
      cervical mucopus and a significantly lower absolute CD4 cell count (354 vs. 469,
      P < .001). An absolute CD4 cell count <200 was associated with a 9.6-fold
      increased odds of cervical HIV-1 DNA detection compared with a count > or = 500
      (95% confidence interval, 2.8-34.2). Detection of vaginal HIV- 1 DNA was
      associated with abnormal vaginal discharge, lower absolute CD4 cell count, and
      severe vitamin A deficiency. Presence of HIV-1-infected cells in genital
      secretions was associated with immunosuppression and abnormal cervical or vaginal
      discharge.

PMID- 8985198
TI  - Importance of genotypic and phenotypic tolerance in the treatment of experimental
      endocarditis due to Streptococcus gordonii.
AB  - Genotypic and phenotypic tolerance was studied in penicillin treatment of
      experimental endocarditis due to nontolerant and tolerant Streptococcus gordonii
      and to their backcross transformants. The organisms were matched for in vitro and
      in vivo growth rates. Rats with aortic endocarditis were treated for 3 or 5 days,
      starting 12, 24, or 48 h after inoculation. When started at 12 h, during fast
      intravegetation growth, 3 days of treatment cured 80% of the nontolerant parent
      compared with <30% of the tolerant derivative (P < .005). When started at 24 or
      48 h and if intravegetation growth had reached a plateau, 3 days of treatment
      failed against both bacteria. However, a significant difference between the 2
      organisms was restored when treatment was extended to 5 days. Thus, genotypic
      tolerance conferred a survival advantage in both fast- and slow-growing bacteria,
      demonstrating that the in vitro-defined tolerant phenotype also carried the risk
      of treatment failure in vivo.

PMID- 8985199
TI  - Receptor affinity purification of a lipid-binding adhesin from Haemophilus
      influenzae.
AB  - Thirteen clinical strains of Haemophilus influenzae, including types b, d, and
      untypeable, in vitro specifically recognize phosphatidylethanolamine (PE),
      gangliotetraosylceramide, gangliotriosylceramide (Gg3),
      sulfatoxygalactosylceramide, and to a lesser extent sulfatoxygalactosylglycerol.
      A PE affinity matrix was used to purify an adhesin of approximately 46 kDa from
      both type b and untypeable H. influenzae. This adhesin was a potent inhibitor of
      H. influenzae Gg3 and PE binding in vitro, and polyclonal antibodies specific for
      this protein prevented the attachment of H. influenzae Gg3 and PE and cultured
      HEp-2 epithelial cells in vitro.

PMID- 8985200
TI  - Primary human immune response to Neisseria meningitidis serogroup C in
      interleukin-12-treated severe combined immunodeficient mice engrafted with human
      peripheral blood lymphocytes.
AB  - Lack of primary immune response in severe combined immunodeficient (SCID) mice
      engrafted with human peripheral blood lymphocytes (hu-PBL) has limited the
      applicability of this model. Use of human cytokines, in particular interleukin
      (IL)-12, was studied in the hu-PBL-SCID model. SCID mice were treated with IL-12
      and reconstituted with hu-PBL in T replacement factor. The hu-PBL-SCID mice were
      immunized with serogroup C meningococcal polysaccharide (MCPS). The MCPS-specific
      antibody response was determined by ELISA. Thirteen of the 15 immunized, IL-12
      treated hu-PBL-SCID mice demonstrated a primary human antibody response to MCPS
      ranging from 0.25 to 3.3 microg/mL, while no MCPS-specific antibody response was
      detectable in the 18 controls. Expression of cross-reactive idiotypic markers
      found on human anti-MCPS antibodies in the immunized hu-PBL-SCID mice was similar
      to that observed in immunized volunteers.

PMID- 8985201
TI  - An OspA-based DNA vaccine protects mice against infection with Borrelia
      burgdorferi.
AB  - Immunization with recombinant OspA protein of Borrelia burgdorferi protects
      against experimental Lyme disease. In the present study, mice were injected
      intramuscularly with plasmid DNA (VR2210) encoding strain B31 OspA. In this
      vector, the ospA-coding sequence was under transcriptional control of the
      cytomegalovirus immediate early promoter. For negative and positive controls,
      mice were immunized with either the plasmid vector without an osp-coding sequence
      or recombinant OspA protein, respectively. Mice immunized with VR2210 DNA
      produced OspA-specific antibodies that bound to B. burgdorferi in a whole cell
      ELISA and inhibited the growth of a homologous strain of B. burgdorferi.
      Immunization with VR2210 protected mice against challenge with 2 infectious
      strains of B. burgdorferi, Sh-2-82 and N40. These results indicate that
      vaccination with plasmid DNA expressing OspA is an efficacious method for
      providing a protective response against B. burgdorferi infection.

PMID- 8985202
TI  - Genetic heterogeneity of Borrelia burgdorferi in the United States.
AB  - To examine in detail Borrelia burgdorferi strain diversity in the United States,
      186 isolates from human, tick, and rodent sources were analyzed from multiple
      distinct geographic regions of the United States and abroad. Strains were
      characterized by genomic macrorestriction analysis and ospA and 23S rDNA gene
      sequencing followed by phylogenetic analysis. Results indicate that spirochetal
      isolates from the United States fall into two major divisions and nine or more
      subdivisions; human isolates fell into five of these subdivisions. Greater
      genetic diversity was observed among B. burgdorferi isolates from moderate
      climatic regions, consistent with increased tick vector and reservoir diversity.
      All of the Borrelia isolates were reactive by ospA polymerase chain reaction
      except for Borrelia hermsii controls and several tick isolates from the
      Northeast, which were shown to lack the 49-kb plasmid encoding outer surface
      protein A (OspA). The data suggest that US B. burgdorferi isolates demonstrate
      substantial genetic heterogeneity, with regional differences in spirochete
      populations.

PMID- 8985203
TI  - Bactericidal/permeability-increasing protein release in whole blood ex vivo:
      strong induction by lipopolysaccharide and tumor necrosis factor-alpha.
AB  - In this study, the release of bactericidal/permeability-increasing protein (BPI),
      which is stored in polymorphonuclear leukocytes (PMNL), was analyzed in a whole
      blood ex vivo system. Of the microbial products tested, lipopolysaccharide (LPS)
      most potently induced BPI release; FMLP, serum-treated zymosan (STZ), and
      lipoteichoic acid (LTA) also induced BPI release. In addition, the inflammatory
      mediator tumor necrosis factor (TNF)-alpha potently activated PMNL in whole
      blood, via TNF receptor p55, to release BPI, whereas interleukin (IL)-1, IL-8,
      platelet activating factor, and C5a were poor inducers of BPI release. STZ and
      phorbol myristate acetate, but not LPS, FMLP, or LTA, stimulated isolated PMNL to
      release BPI. BPI was released in comparable magnitude with the azurophilic
      granule protein elastase. Furthermore, both proteins were released with similar
      kinetics, which started within 30 min after onset of stimulation and lasted 1-4
      h.

PMID- 8985204
TI  - Antiinflammatory cytokine responses during clinical sepsis and experimental
      endotoxemia: sequential measurements of plasma soluble interleukin (IL)-1
      receptor type II, IL-10, and IL-13.
AB  - Plasma concentrations of soluble interleukin (IL)-1 receptor type II, IL-10, and
      IL-13 were measured in 42 patients with clinically defined sepsis during a 3-day
      follow-up and in 7 healthy humans after intravenous injection of endotoxin (2
      ng/kg). Levels of soluble IL-1 receptor type II were persistently elevated in
      patients with sepsis than in healthy controls and higher in nonsurviving patients
      (n = 22) than in surviving patients (n = 20) at all time points. IL-10 was found
      in the circulation of 81% of patients with sepsis, while it was not detectable in
      normal plasma. During follow-up, IL-10 remained invariably high only in
      nonsurviving patients, while it significantly decreased in survivors. Endotoxin
      induced IL-10, while soluble IL-1 receptor type II remained unchanged. IL-13
      remained undetectable in the vast majority of patients and was not induced by
      endotoxin. Enhanced IL-13 production does not seem to be part of an inducible
      host defense mechanism during sepsis.

PMID- 8985205
TI  - Interaction with autologous platelets multiplies interleukin-1 and tumor necrosis
      factor production in mononuclear cells.
AB  - The effect of activated platelets on cytokine production by human peripheral
      blood mononuclear cells (PBMC) was investigated. When PBMC were coincubated with
      activated autologous platelets amid lipopolysaccharide (LPS, 50-100 pg/mL) for 8
      h, the production of interleukin (IL)-1alpha increased 11- to 18-fold and tumor
      necrosis factor (TNF)-alpha 3- to 5-fold compared with PBMC without platelets.
      Activated platelets in a dual-chamber well that prevented platelet-PBMC contact
      but permitted passage of soluble factors enhanced IL-1alpha production (P < .01).
      Platelet-PBMC contact in the chamber resulted in a further enhancement of IL
      1alpha production. These data suggest that platelet-PBMC interaction, both
      directly and with platelet-derived factors, enhances production of shock
      producing IL-1alpha and TNF-alpha, albeit differently. The interaction of
      platelets with monocytes may play an important role in the pathophysiology of
      sepsis and disseminated intravascular coagulation.

PMID- 8985206
TI  - Nitrite generation in interleukin-4-treated human macrophage cultures does not
      involve the nitric oxide synthase pathway.
AB  - The search continues for high-output nitric oxide biosynthesis in human
      macrophages analogous to murine phagocytes. Recently, generation of nitrite in
      culture supernatants of human macrophages exposed to interferon-gamma and
      interleukin-4 (IFN-gamma/IL-4) was reported. The present study reproduces these
      findings and shows that L-arginine is not consumed and L-citrulline is not
      produced during this process. Furthermore, the biosynthesis of the obligatory
      cofactor tetrahydrobiopterin is not coinduced. These biochemical data provide
      support against a nitric oxide synthase contribution to nitrite accumulation.
      Nitrite was generated from nitrate salts even in cell-free media. Nitric oxide
      synthase activity but not nitrate reduction depended on molecular oxygen. Nitrite
      accumulation in experiments with IFN-gamma/IL-4 in human monocytes appears to be
      an in vitro artifact produced by nitrate-reducing activities contained in
      cytokine preparations.

PMID- 8985207
TI  - Immune responses associated with chronic fatigue syndrome: a case-control study.
AB  - An exploratory case-control study was conducted to assess whether the many
      reported differences in the immune function of chronic fatigue syndrome (CFS)
      patients are detectable in rigorously defined cases of CFS. Although many studies
      have reported differences between cases and controls in various measures of
      immune function, none of these differences were found in all studies. In this
      study, no differences were found in white blood cell numbers; immune complex,
      complement, or serum immunoglobulin levels; delayed type hypersensitivity and
      allergic responses; NK cell function; and proliferative responses to mitogens and
      antigens. Marginal differences were detected in cytokine responses and in cell
      surface markers in the total CFS population. However, when the patients were
      subgrouped by type of disease onset (gradual or sudden) or by how well they were
      feeling on the day of testing, more pronounced differences were seen.

PMID- 8985208
TI  - Alteration of interleukin-2 (IL-2) and soluble IL-2 receptor secretion in the
      sera and urine of patients with rickettsial boutonneuse fever.
AB  - Sera and urine samples from 115 Sicilian patients with boutonneuse fever (BF),
      obtained at the time of diagnosis and after clinical recovery, were analyzed for
      concentrations of interleukin (IL)-2 and soluble IL-2 receptor (sIL-2R). There
      were significantly high levels of sIL-2R in the urine and sera of patients with
      acute BF compared with healthy controls, and the values returned to normal
      following successful chemotherapy. The data indicate that the sIL-2R urine
      concentrations correlated directly with the sIL-2R sera levels. In contrast, in
      all tested sera and urine samples, IL-2 levels were normal. Furthermore, a
      reduction in IL-2 production by peripheral blood mononuclear cells from acute BF
      patients was also observed. sIL-2R represents an unspecific marker useful to
      monitor the evolution of BF.

PMID- 8985209
TI  - Binding and germination of Aspergillus fumigatus conidia on cultured A549
      pneumocytes.
AB  - Invasive pulmonary aspergillosis is acquired through inhalation of conidia.
      Little is known about early interactions between Aspergillus fumigatus conidia
      and alveolar epithelial cells, so an in vitro model was developed to study
      binding between conidia and A549 cells, a line of type II pneumocytes. Conidia
      rapidly became attached to confluent monolayers of A549 cells in serum-free
      medium, reaching a plateau within 40 min. Scanning electron microscopy (EM)
      showed a random pattern of early adherence; viable conidia subsequently became
      clustered on pneumocyte surfaces. Following germination of pneumocyte-adherent
      conidia for 12 h, direct penetration of epithelial cells by hyphae could be
      demonstrated by scanning and transmission EM. These data suggest that an early
      event following inhalation of A. fumigatus conidia may be binding of conidia to
      pneumocytes, followed by hyphal penetration of the epithelial cell layer.

PMID- 8985210
TI  - The influence of antigen-presenting cell type and interferon-gamma on priming and
      cytokine secretion of Leishmania major-specific T cells.
AB  - A Leishmania major-specific primary in vitro system that mimics the immune
      response of infected mice was used to determine the role that dendritic cells, B
      cells, and macrophages play in L. major T cell priming. Their relative priming
      potential (in order) was dendritic cells, B cells, and macrophages. Initiating
      primary in vitro responses with cell populations depleted of either B or
      dendritic cells modestly enhanced interferon (IFN)-gamma production; deleting
      both cells markedly enhanced IFN-gamma production. Thus, macrophages were the
      most effective cell for eliciting L. major Th1 cells. The effects of exogenously
      added IFN-gamma or neutralizing anti-IFN-gamma were also studied. With cells from
      genetically susceptible BALB/c mice, IFN-gamma inhibited proliferation and
      interleukin-4 secretion by T cells, whereas with resistant C57BL/6 cells, IFN
      gamma enhanced IFN-gamma secretion. These results could not be explained by
      differences in IFN-gamma receptor expression.

PMID- 8985211
TI  - High levels of parasite-specific IgG1 correlate with the amicrofilaremic state in
      Loa loa infection.
AB  - To investigate the mechanisms of protective immunity operating in Loa loa
      infection, 56 persons from a L. ioa-endemic village in southeast Gabon were
      examined over a 7-year period. The level of L. loa-specific IgG subclasses in
      defined parasitologic groups was compared by use of ELISA with either adult,
      microfilarial, or third-stage larval (L3) antigens of L. loa. With all antigen
      preparations, IgG1 levels were significantly higher in amicrofilaremic persons
      than in persons with high or low levels of microfilariae. Moreover, there was a
      significant negative correlation between IgG1 levels to L3 antigen and the
      density of microfilariae (Spearman's r(s) = -.701; P < .01). There was no
      correlation between density of microfilariae and levels of other IgG subclasses
      or of IgE. These data indicate that IgG1 may play a role in the effector
      mechanism(s) involved in resistance against L. loa and suggest that L3 antigens
      may be important in eliciting protective responses.

PMID- 8985212
TI  - The association between hepatitis C virus genotype and human immunodeficiency
      virus disease progression in a cohort of hemophilic men.
AB  - Patients coinfected with both hepatitis C virus (HCV) and the human
      immunodeficiency virus (HIV) have more rapid progression of HCV infection;
      however, little is known about the effect of coinfection with HCV on the
      progression of HIV disease. This study assessed the association between infection
      with different HCV genotypes on progression to AIDS and death in a cohort of men
      with hemophilia. Patients infected with HCV type 1 experienced a more rapid
      progression to both AIDS (P = .009) and death (P = .007) than did those infected
      with other types. This effect was largely independent of age at seroconversion,
      hemophilia diagnosis, and changes in CD4 cell count over the follow-up period.
      These results suggest an association between HCV genotype and progression of HIV
      disease, which, if confirmed, could have important implications for the treatment
      and care of patients coinfected with both HIV and HCV.

PMID- 8985213
TI  - GB virus C/hepatitis G virus infection in southern China.
AB  - The prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection among
      intravenous drug users (IVDUs), patients with liver diseases, and blood donors in
      Nanning, southern China was studied. GBV-C/HGV RNA was detected by reverse
      transcription polymerase chain reaction with primers derived from the 5'
      untranslated region. GBV-C/HGV RNA was detected in 64 of 85 IVDUs, 20 of 80
      persons with liver disease, and 1 of 50 blood donors. Among IVDUs, GBV-C/HGV
      infection was associated with antibodies to hepatis C virus (HCV) and with
      hepatitis B surface antigen (HBsAg). Eleven nucleotide sequences were determined
      and analyzed by molecular evolutionary analysis. In a phylogenetic tree, the
      isolates were grouped in three clusters with GBV-C and HGV grouped in two
      clusters. These data indicate that GBV-C/HGV infection is common in China among
      IVDUs but uncommon among persons with liver disease without HBsAg or anti-HCV and
      that there is a new group of GBV-C/HGV.

PMID- 8985214
TI  - Maternal virus load during pregnancy and mother-to-child transmission of human
      immunodeficiency virus type 1: the French perinatal cohort studies. SEROGEST
      Cohort Group.
AB  - Virus load in pregnancy and its relation to mother-to-child human
      immunodeficiency virus (HIV) transmission were studied prospectively. From 1989
      to 1994, 320 HIV-infected women from 18 centers had plasma samples stored. Among
      women not receiving antiretroviral therapy, the polymerase chain reaction RNA
      level was 3.6 log at delivery, and 15% of women had levels below the detection
      limit. There was no variation during pregnancy. Women born in sub-Saharan Africa
      had lower RNA levels, although their CD4 cell distribution did not differ from
      that in other women. Among 236 evaluable children, 19% +/- 5% were infected.
      Transmission occurred in 12% of cases (confidence interval, 5%-22%) with <1000
      copies/mL versus 29% +/- 10% of those with >10,000 copies/mL (P < .02). Maternal
      virus load appears strongly related to HIV transmission to the child.

PMID- 8985215
TI  - Drug sensitivity of human immunodeficiency virus type 1 isolates after ribavirin
      therapy.
AB  - The antiviral agent ribavirin is effective against several virally induced
      diseases, and there is evidence that it might prove useful against human
      immunodeficiency virus type 1 (HIV-1) infection. Thus, there is interest in
      studying the resistance level of HIV-1 isolates to ribavirin following drug
      therapy. Low-passage clinical strains of HIV-1 were isolated from 3 patients
      undergoing treatment with ribavirin for 5-9 months. No significant changes in
      drug sensitivity were seen for sequential virus samples obtained before, during,
      and after antiviral therapy. These observations suggest that the appearance of a
      resistant phenotype is not induced by treatment with ribavirin in HIV-1-infected
      persons.

PMID- 8985216
TI  - Cytomegalovirus gB genotype distribution differs in human immunodeficiency virus
      infected patients and immunocompromised allograft recipients.
AB  - Cytomegalovirus isolates can be grouped into 4 gB and 2 gH genotypes. gB
      genotypes were studied in patients infected with human immunodeficiency virus
      (HIV) and in allograft transplantation recipients. In allograft recipients, the
      distribution of gB 1, -2, -3, and -4 in leukocytes and urine, respectively, was
      36%, 21%, 43%, and 0% and 39%, 30%, 17%, and 13%. However, in leukocytes of HIV
      infected patients with <100/microL CD4 cells, gB1 was found significantly less
      often than in allograft recipients (11% vs. 36%) but gB2 was more frequent (56%
      vs. 21%; P < .05). The decreased incidence of gBl and increased incidence of gB2
      compared with allograft recipients was also seen in urine of HIV-infected
      patients and reflected the distribution seen in leukocytes. gB4 was found
      significantly more often (P < .05) in semen than in leukocytes of HIV-infected
      patients with < 100/microL CD4 cells. gB1-4 genotypes were similar in patients
      with < 100/microL CD4 cells with or without retinitis.

PMID- 8985217
TI  - Simian immunodeficiency virus-inoculated macaques acquire Mycobacterium avium
      from potable water during AIDS.
AB  - During the terminal stages of AIDS, Mycobacterium avium complex (MAC) infection
      is the most common disseminated bacterial infection in rhesus macaques (Macaca
      mulatta) experimentally inoculated with the simian immunodeficiency virus (SIV).
      The source of mycobacterial infection in 15 SIV-inoculated rhesus macaques housed
      in a biolevel 3 containment facility was investigated using a sensitive
      polymerase chain reaction typing technique. Six animal isolates had banding
      profiles identical to that of 1 environmental isolate obtained from the
      facility's water distribution system. An additional 6 isolates had banding
      profiles differing by the addition or loss of one or two bands from this and 1
      other water isolate. These findings indicate that potable water may serve as a
      significant source of mycobacterial infection in SIV-inoculated macaques and
      suggest that strategies to prevent exposure to mycobacteria within potable water
      should be investigated as a method to prevent mycobacteriosis in human
      immunodeficiency virus-infected persons.

PMID- 8985218
TI  - Polymorphisms within the human tumor necrosis factor-alpha promoter region in
      human immunodeficiency virus type 1-seropositive persons.
AB  - The question is addressed whether particular tumor necrosis factor-alpha (TNF
      alpha) polymorphisms are associated with clinical course and outcome of human
      immunodeficiency virus type 1 (HIV-1) infection. The distribution of four TNF
      alpha guanine (G) to adenosine (A) transition polymorphisms at positions -376, 
      308, -238, and -163 of the 5' promoter region of the TNF-alpha gene was studied
      in a nested case-control study among HIV-1-seropositive participants of the
      Amsterdam Cohort. None of the polymorphisms was significantly associated with
      long-term asymptomatic survival after HIV-1 infection compared with progression
      to clinical AIDS. Moreover, specific AIDS-defining illnesses or biologic
      phenotype of the HIV-1 virus were not associated with TNF-alpha alleles. The
      results of this study do not point toward a role for known TNF-alpha G to A
      transition polymorphisms in the clinical course of HIV-1 infection.

PMID- 8985219
TI  - Circulating and ex vivo production of pyrogenic cytokines and interleukin-1
      receptor antagonist in 123 patients with fever of unknown origin. The Netherlands
      Fever of Unknown Origin Study Group.
AB  - Circulating and ex vivo production of interleukin (IL)-1beta, tumor necrosis
      factor (TNF)-alpha, IL-6, and IL-1 receptor antagonist (ra) and the diagnostic
      utility of these cytokines were studied in 123 patients with fever of unknown
      origin (FUO). Diagnoses were infections, 28; neoplasms, 14; noninfectious
      inflammatory diseases (NIID), 32; miscellaneous diseases, 10; and none made, 39.
      IL-1beta, IL-6, and IL-1ra concentrations were higher in patients with
      infections, neoplasms, and NIID than in healthy controls. Patients with
      infections had higher concentrations of TNF-alpha than controls. The ex vivo
      production of IL-1beta and IL-1ra in all patients with FUO did not differ from
      that in controls; however, production of TNF-alpha was lower in patients with
      neoplasms and NIID, and IL-6 production was lower in patients with neoplasms.
      Thirty-five patients with fever did not have elevated cytokines. Although some
      significant differences were found among the diagnostic subgroups, there was wide
      variation. Thus, measurement of these cytokines does not aid in the diagnosis of
      FUO.

PMID- 8985220
TI  - Diagnosis of measles with an IgM capture EIA: the optimal timing of specimen
      collection after rash onset.
AB  - The optimal timing for collection of a single serum specimen to diagnose measles
      by using a monoclonal antibody-capture EIA was evaluated. Results of testing
      paired serum samples from 166 measles cases with at least 1 IgM-positive specimen
      were analyzed. Among persons whose second samples were IgM-positive, the
      seropositivity rate for first samples was 77% when collected within 72 h and 100%
      when collected 4-11 days after rash onset. Among unvaccinated persons whose first
      samples were IgM-positive, the rate for IgM positivity of second specimens
      declined from 100% at 4 days to 94% at 4 weeks after rash onset, then declined
      further to 63% at 5 weeks. Some previously vaccinated persons became IgM-negative
      during the third week after rash onset. In general, a single serum specimen
      collected between 72 h and 4 weeks after rash onset can be used to diagnose most
      cases of measles with an IgM capture EIA.

PMID- 8985221
TI  - Induction of immunologic memory in Gambian children by vaccination in infancy
      with a group A plus group C meningococcal polysaccharide-protein conjugate
      vaccine.
AB  - Two hundred twenty-one Gambian children vaccinated previously with one, two, or
      three doses of a meningococcal conjugate vaccine or two doses of polysaccharide
      vaccine before the age of 6 months were revaccinated at the age of 18-24 months
      with either meningococcal polysaccharide, conjugate, or inactivated polio
      vaccines. Children who had previously received one, two, or three doses of
      conjugate vaccine had significantly (P < .001) higher anti-group C meningococcal
      antibody levels following revaccination than did children vaccinated with a
      polysaccharide vaccine for the first time. Children vaccinated previously with
      two doses of polysaccharide vaccine had a lower group C antibody response than
      did control children. Group A antibody responses following revaccination of
      children who had previously received polysaccharide or conjugate vaccine were not
      significantly higher than those in control children. Thus, immunologic memory was
      probably induced by the group C but not by the group A component of the conjugate
      vaccine.

PMID- 8985222
TI  - New murine model of bronchopneumonia due to cell-bound Haemophilus influenzae.
AB  - This murine model of nontypeable (unencapsulated) Haemophilus influenzae (NTHI)
      bronchopneumonia used organisms bound to mouse fetal lung (MFL) cells as an
      inoculum. Pretreatment of the mice with 40 microL of 1% formalin 3 days before
      intranasal instillation of the bacteria was necessary to allow infection. The
      number of NTHI recovered from the lungs plus trachea on day 7 after instillation
      was >100 times the number originally inoculated. Later, however, the number of
      recovered bacteria diminished gradually, and by day 14 it was almost identical to
      the original inoculum size. Serum IgM also peaked on day 7 after infection, after
      which IgG increased while IgM decreased. Histologically, bronchoalveolar
      infiltration of neutrophils was observed on day 3 after inoculation and continued
      at least for the following 4 days. The present experiment demonstrates that MFL
      cells can protect bacteria that have invaded the cells from the opsonizing and
      killing activities of host humoral defense mechanisms.

PMID- 8985224
TI  - Role of macrophages in the candidacidal activity of liposomal amphotericin B.
AB  - The role of macrophage activation in the candidacidal activity of liposome
      incorporated (L) amphotericin B was investigated. Macrophages treated with L
      amphotericin B killed Candida albicans more effectively than did macrophages
      treated with free (F) amphotericin B. However, macrophages treated with neither F
      nor L-amphotericin B killed amphotericin B-resistant Candida tropicalis. In vivo
      stimulation of macrophages by intraperitoneal administration of thioglycollate,
      Freund's complete adjuvant, or heat-killed C. albicans followed by in vitro
      treatment with F- or L-amphotericin B, did not enhance their candidacidal
      activity. Intravenous administration of F- or L-amphotericin B did not augment
      the candidacidal activity of macrophages sensitized in vivo; however, sensitized
      macrophages showed enhanced killing compared with resident unstimulated cells.
      These studies suggest that macrophage-mediated enhancement of C. albicans killing
      may be due to uptake, transport, and delivery of L-amphotericin B to infected
      sites rather than to macrophage activation.

PMID- 8985223
TI  - Ultrastructural and antigenic characterization of a granulocytic ehrlichiosis
      agent directly isolated and stably cultivated from a patient in New York state.
AB  - A human granulocytic ehrlichiosis (HGE) agent with 16S rDNA sequence identical to
      the published sequence of HGE agents was isolated from a patient from New York
      State by inoculation of the blood leukocyte fraction directly into a human
      promyelocytic leukemia cell line HL-60. The HGE agent was also isolated from the
      leukocyte fraction of the blood and bone marrow of a mouse inoculated with the
      leukocyte fraction of the patient's blood. The isolate has been passaged in
      tissue culture 30 times over 8 months. Electron microscopy revealed pleomorphic
      coccobacilli with a thin and highly rippled outer membrane in the clear inclusion
      matrix. Comparison of IFA reactivity of antisera obtained from a variety of
      sources with the cell-cultured HGE agent revealed that 3 HGE agent strains (New
      York isolate, Wisconsin [BDS] isolate, and a tick-derived isolate) are highly
      cross-reactive and there are diverse antigenic cross-reactivities between HGE
      agent and Ehrlichia chaffeensis.

PMID- 8985225
TI  - Effect of Lactobacillus reuteri on intestinal resistance to Cryptosporidium
      parvum infection in a murine model of acquired immunodeficiency syndrome.
AB  - Efficacy of Lactobacillus reuteri as a probiotic for the control of
      Cryptosporidium parvum infection was evaluated in C57BL/6 female mice that were
      immunosuppressed by intraperitoneal inoculation with the LP-BM5 leukemia virus.
      Four months after inoculation, mice developed lymphadenopathy, splenomegaly, and
      susceptibility to C. parvum infection. After daily prefeeding with L. reuteri
      (10(8) cfu/day) for 10 days, mice were challenged with 6.5 x 10(6) C. parvum
      oocysts and fed L. reuteri during the entire study. Mice supplemented with L.
      reuteri and challenged with C. parvum cleared parasite loads from the gut
      epithelium. However, unsupplemented animals developed persistent
      cryptosporidiosis and shed high levels of oocysts in the feces. L. reuteri
      feeding increased its colonization of the intestinal tract, which was inversely
      related to the fecal shedding of oocysts. These findings suggest that L. reuteri
      may help prevent C. parvum infection in immunodeficient subjects.

PMID- 8985226
TI  - Invasive aspergillosis in mice immunosuppressed with cyclosporin A, tacrolimus
      (FK506), or sirolimus (rapamycin).
AB  - Cyclosporin A, tacrolimus, and sirolimus are immunosuppressive agents initially
      described as antifungal compounds with different activities for Aspergillus
      species. The outcome of invasive aspergillosis in mice treated with each agent
      was investigated in outbred CD-1 mice. Immunosuppressant or vehicle alone was
      administered from days -1 to +14. Mice were infected on day 0 with resting
      Aspergillus conidia via lateral tail vein injection. Survival was significantly
      greater with most regimens than for mice treated with cyclosporin A (100
      mg/kg/day; median survival, 3 days): tacrolimus, 1 mg/kg/day (6.5 days, P =
      .003); sirolimus, 1 or 10 mg/kg/day (7.5 and 9.5 days, respectively; P = .002 and
      .0001); and vehicle alone (6.5 days, P = .001). However, mice treated with 10
      mg/kg/day of tacrolimus survived a median of 4.5 days (P = .25). Survival in the
      10-mg sirolimus group did not differ from that of mice given vehicle alone (P =
      .55). Histologic evaluation suggested the improved survival with tacrolimus and
      sirolimus may be due in part to direct anti-Aspergillus activity.

PMID- 8985227
TI  - Modulatory potential of iron chelation therapy on nitric oxide formation in
      cerebral malaria.
AB  - To determine whether iron chelation modulates nitric oxide (NO) formation and
      cell-mediated immune effector function in children with cerebral malaria, serum
      concentrations were measured of the stable end products of NO, nitrite and
      nitrate (NO2-/NO3-), interleukin (IL)-4, -6, and -10, and neopterin in 39 Zambian
      children enrolled in a placebo-controlled trial of desferrioxamine B and quinine
      therapy. Mean concentrations of NO2-/NO3- increased significantly over 3 days in
      children receiving desferrioxamine plus quinine but not in those given placebo
      and quinine. Neopterin levels declined significantly with placebo but not with
      desferrioxamine. IL-4 levels increased progressively in the placebo group and
      ultimately decreased in the desferrioxamine group, but the trends were not
      statistically significant. IL-6 and IL-10 levels were elevated initially and
      decreased significantly in both groups over 3 days. These data are consistent
      with the hypothesis that iron chelation therapy in children with cerebral malaria
      strengthens Th1-mediated immune effector function involving increased production
      of NO.

PMID- 8985228
TI  - Appearance of autologous neutralizing antibody correlates with reduction in virus
      load and phenotype switch during primary infection with human immunodeficiency
      virus type 1.

PMID- 8985230
TI  - Risk and the inadequacy of science.

PMID- 8985229
TI  - Importance of using relapse studies or tests for detection of antibiotic
      resistance before considering that a treatment for multidrug-resistant
      enterococcal experimental endocarditis is effective.

PMID- 8985231
TI  - Time honours AIDS pioneer.

PMID- 8985232
TI  - How BSE crisis forced Europe out of its complacency.

PMID- 8985234
TI  - German resistance to genetic engineering diminishes.

PMID- 8985233
TI  - UK policy learns about risk the hard way.

PMID- 8985235
TI  - Blood scandal and E. coli raise questions in Japan.

PMID- 8985236
TI  - Voice of US science struggles to be heard.

PMID- 8985237
TI  - The moral ape.

PMID- 8985238
TI  - Eighteen-ninety-seven and all that.

PMID- 8985239
TI  - A protein-making motor protein.

PMID- 8985240
TI  - Axons follow Reelin routes.

PMID- 8985241
TI  - Mary Leakey 1913-96.

PMID- 8985242
TI  - Biology's new Rosetta stone.

PMID- 8985243
TI  - Y chromosomes of Jewish priests.

PMID- 8985244
TI  - Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome.
AB  - Elongation factor G (EF-G) is a GTPase that is involved in the translocation of
      bacterial ribosomes along messenger RNA during protein biosynthesis. In contrast
      to current models, EF-G-dependent GTP hydrolysis is shown to precede, and greatly
      accelerate, the rearrangement of the ribosome that leads to translocation. Domain
      IV of the EF-G structure is crucial for both rapid translocation and subsequent
      release of the factor from the ribosome. By coupling the free energy of GTP
      hydrolysis to translocation, EF-G serves as a motor protein to drive the
      directional movement of transfer and messenger RNAs on the ribosome.

PMID- 8985245
TI  - Acceleration of a Diels-Alder reaction by a self-assembled molecular capsule.
AB  - The interior of cage-like molecules can be considered to provide a new phase of
      matter, in which it becomes possible to stabilize reactive intermediates and to
      observe new forms of stereoisomerism. Cage-like molecular complexes that self
      assemble through weak intermolecular forces are dynamic species, encapsulating
      guest molecules reversibly. They can persist over timescales ranging from
      microseconds to hours, long enough for chemical processes to take place within
      them. Here we report the acceleration of a Diels-Alder reaction by encapsulation
      of the reactants in a self-assembling molecular capsule. Although product
      inhibition (lack of dissociation) prevents the system from showing true catalytic
      behaviour, there is clear evidence for a rate increase of over two orders of
      magnitude owing to the effective enhancement of concentration inside the capsule.

PMID- 8985246
TI  - The Drosophila protein Wunen repels migrating germ cells.
AB  - In Drosophila, germ cells migrate in embryonic development from the lumen of the
      developing gut towards the overlying mesoderm, where they enter the gonads. The
      gene wunen is responsible for guiding the germ cells early in this process. Here
      we report that the protein Wunen has two properties that allow it to use
      repulsion to guide the germ cells. Wunen can transform a permissive cellular
      environment into a repulsive one, and is expressed in the gut in a pattern that
      guides germ cells towards the mesoderm. Wunen shows strong similarity to the
      enzyme type 2 phosphatidic acid phophatase (PAP2)4, suggesting that it is
      involved in lipid metabolism.

PMID- 8985247
TI  - Regulation of neuronal diversity in the Xenopus retina by Delta signalling.
AB  - To generate the variety of mature neurons and glia found in the developing
      retina, the competence of pluripotent progenitor cells to respond to
      extracellular signals must be controlled. Delta, a ligand of the Notch receptor,
      is a candidate for regulating progenitor competence on the grounds that
      activation of the pathway involving Notch and Delta can inhibit cellular
      differentiation. Here we test this possibility in the developing Xenopus retina
      by misexpression of Delta messenger RNA. We find that Delta-misexpressing cells
      with wild-type neighbours adopt earlier fates, primarily becoming ganglion cells
      and cone photoreceptors. Progenitors transfected with Delta later in development
      also produce rod photoreceptors, but not the latest-generated cell types,
      demonstrating the importance of timing in Delta function. We conclude that Delta
      signalling in the vertebrate retina is a basic regulatory mechanism that can be
      used to generate neuronal diversity.

PMID- 8985248
TI  - A role for Cajal-Retzius cells and reelin in the development of hippocampal
      connections.
AB  - During development of the nervous system, specific recognition molecules provide
      the cues necessary for the formation of neural connections. In some regions,
      guiding cues for axonal pathfinding and target selection are provided by specific
      cells that exist only transiently during development, such as the floorplate or
      the cortical subplate. In the hippocampus, distinct groups of fibres innervate
      different layers. We have tested the hypothesis that transient neurons in the
      hippocampus provide positional information for the targeting of these fibres.
      Here we report that ablation of Cajal-Retzius cells in organotypic slice cultures
      of hippocampus prevented the ingrowth of entorhinal but not of commissural
      afferents. Experiments inhibiting Reelin (an extracellular matrix protein
      expressed by Cajal-Retzius cells) and analysis of reeler mutant mice showed
      dramatic abnormalities in the development of entorhinal afferents. Thus Cajal
      Retzius cells and reelin are essential for the formation of layer-specific
      hippocampal connections.

PMID- 8985249
TI  - Frequency detection and temporally dispersed synaptic signal association through
      a metabotropic glutamate receptor pathway.
AB  - In the classical view, a central neuron integrates incoming synaptic information
      by simple algebraic summation of the resultant bioelectrical signals that
      coincide in time. The voltage dependence of the NMDA (N-methyl-D-aspartate) type
      of ionotropic glutamate receptor endows neurons with an additional tool that
      allows one synaptic input to influence another, providing, again, that the two
      are active simultaneously. Here we identify a new mechanism by which non
      coincident signals generated by different synaptic inputs are integrated. The
      device serves to regulate neuronal excitation through G-protein-coupled,
      metabotropic glutamate receptors (mGluRs) in a powerful and specific manner. We
      show that, in cerebellar Purkinje cells, a single activation of the climbing
      fibre input markedly potentiates mGluR-mediated excitation at parallel-fibre
      synapses. The potentiation results from a transient rise in cytosolic Ca2+ which
      is 'memorized' in such a way that it promotes excitation through mGluRs for about
      two minutes. A Ca2+-transient is also effective if imposed up to two seconds
      after parallel-fibre stimulation. By allowing temporally and spatially dispersed
      synaptic signals to be assimilated, this mechanism adds a new element to the
      computational power of central neurons.

PMID- 8985250
TI  - Potent antitumour activity of a new class of tumour-specific killer cells.
AB  - Two approaches to the antibody-directed targeting of toxic or cytolytic activity
      and augmentation of cellular immune responses have been explored for tumour
      immunotherapy, but so far success has been limited. Obstacles facing
      immunotherapy are the limited accessibility of antibodies or antibody conjugates
      to solid tumours and the difficulty in obtaining tumour-specific cytotoxic
      lymphocytes. Here we generate a new class of tumour-specific killer cells by
      genetically modifying lymphocytes to produce and secrete a targeted toxin against
      an oncoprotein overexpressed on breast and other tumour cells. The transduced
      lymphocytes were shown to have potent and selective cytotoxicity to tumours in
      culture and nude mouse models. The potent in vivo antitumour activity is probably
      a result of the migration of the lymphocytes to tumours as a targeted toxin
      carrier, and production and accumulation of the targeted toxins inside tumours as
      a producer. Our approach, which has features of both antibody-directed and cell
      mediated immunotherapy, may have application in a gene therapy context.

PMID- 8985251
TI  - P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into
      inflammed tissues.
AB  - When activated, T helper cells differentiate into one of two subsets, Th1 and
      Th2, characterized by distinct profiles of cytokine production. Th1 cells
      activate pro-inflammatory effector mechanisms involved in protection and
      autoimmunity, whereas Th2 cells induce humoral and allergic responses and
      downregulate local inflammation. Apart from differences in the repertoire of
      cytokines, no phenotypic attributes are established that distinguish the two
      subsets. Here we show that Th1 cells, but not Th2 cells, are able to bind to P
      selectin and E-selectin. Moreover, only Th1 cells can efficiently enter inflamed
      sites in Th1-dominated models, such as sensitized skin or arthritic joints, but
      not in a Th2-dominated allergic response. Immigration of Th1 cells into inflamed
      skin can be blocked by antibodies against P- and E-selectin. These results
      provide evidence for adhesion mechanisms to distinguish between the two T helper
      subsets and mediate their differential trafficking. They indicate that selective
      recruitment is an additional level of regulation for both effector function
      profile and character of a local immune response.

PMID- 8985252
TI  - Selective modulation of protein kinase C-theta during T-cell activation.
AB  - Every cell contains many families of protein kinases, and may express several
      structurally related yet genetically distinct kinases of each family. The
      activity of the serine/threonine protein kinase C (PKC) enzymes has long been
      implicated in T-cell activation, but it is not known which members of the PKC
      family regulate the T-cell response to foreign antigens. The activation of T
      cells by antigen-presenting cells (APCs) is spatially restricted to their site of
      contact, where receptors on the T cells engage their counter-receptors on the
      APCs. We used this localized engagement to identify, at the single-cell level,
      intracellular proteins involved in the activation process. By digital
      immunofluorescence microscopy, we localized six isoforms of PKC in antigen
      specific T-cell clones activated by APCs. Surprisingly, only PKC-theta
      translocated to the site of cell contact. Accordingly, in vitro kinase activity
      assays of PKC immunoprecipitates from the conjugates of T cells and APCs showed a
      selective increase in the activity of PKC-theta, indicating that the translocated
      enzyme is active. Several modes of partial T-cell activation that failed to cause
      PKC-theta translocation also failed to cause T-cell proliferation, further
      suggesting the involvement of PKC-theta in T-cell activation.

PMID- 8985253
TI  - RAIDD is a new 'death' adaptor molecule.
AB  - The effector arm of the cell-death pathway is composed of cysteine proteases
      belonging to the ICE/CED-3 family. In metazoan cells these exist as inactive
      polypeptide precursors (zymogens), each composed of a prodomain, which is cleaved
      to activate the protease, and a large and small catalytic subunit. The coupling
      of these 'death' proteases to signalling pathways is probably mediated by adaptor
      molecules that contain protein-protein interaction motifs such as the death
      domain. Here we describe such an adaptor molecule, RAIDD, which has an unusual
      bipartite architecture comprising a carboxy-terminal death domain that binds to
      the homologous domain in RIP, a serine/threonine kinase component of the death
      pathway. The amino-terminal domain is surprisingly homologous with the sequence
      of the prodomain of two ICE/CED-3 family members, human ICH-1 (ref. 5) and
      Caenorhabditis elegans CED-3 (ref. 6). This similar region mediates the binding
      of RAIDD to ICH-1 and CED-3, serving as a direct link to the death proteases,
      indicating that the prodomain may, through homophilic interactions, determine the
      specificity of binding of ICE/CED-3 zymogens to regulatory adaptor molecules.
      Finally, alternations in the sequence of the N-terminal domain that are
      equivalent to inactivating mutations in the C. elegans ced-3 gene prevent
      homophilic binding, highlighting the potentially primordial nature of this
      interaction.

PMID- 8985254
TI  - Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein
      like trimer.
AB  - The platelet-activating factor PAF (1-O-alkyl-2-acetyl-sn-glycero-3
      phosphocholine) is a potent lipid first messenger active in general cell
      activation, fertilization, inflammatory and allergic reactions, asthma, HIV
      pathogenesis, carcinogenesis, and apoptosis. There is substantial evidence that
      PAF is involved in intracellular signalling, but the pathways are poorly
      understood. Inactivation of PAF is carried out by specific intra- and
      extracellular acetylhydrolases (PAF-AHs), a subfamily of phospholipases A2 that
      remove the sn-2 acetyl group. Mammalian brain contains at least three
      intracellular isoforms, of which PAF-AH(Ib) is the best characterized. This
      isoform contains a heterodimer of two homologous catalytic subunits alpha1 and
      alpha2, each of relative molecular mass 26K, and a non-catalytic 45K beta
      subunit, a homologue of the beta-subunit of trimeric G proteins. We now report
      the crystal structure of the bovine alpha1 subunit of PAF-AH(Ib) at 1.7 A
      resolution in complex with a reaction product, acetate. The tertiary fold of this
      protein is closely reminiscent of that found in p21(ras) and other GTPases. The
      active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192.
      Thus, the intact PAF-AH(Ib) molecule is an unusual G-protein-like
      (alpha1/alpha2)beta trimer.

PMID- 8985256
TI  - The cellular pathogenesis of portal hypertension: stellate cell contractility,
      endothelin, and nitric oxide.

PMID- 8985255
TI  - Regulatory intramolecular association in a tyrosine kinase of the Tec family.
AB  - The T-cell-specific tyrosine kinase Itk is a member of the Tec family of non
      receptor tyrosine kinases, and is required for signalling through the T-cell
      antigen receptor (TCR). The role of Itk in TCR signalling and the manner in which
      Itk activity is regulated are not well understood. Substrate binding and
      enzymatic activity of the structurally related Src kinases are regulated by an
      intramolecular interaction between the Src-homology-2 (SH2) domain and a
      phosphotyrosine. Although Itk also contains SH3, SH2 and tyrosine kinase domains,
      it lacks the corresponding regulatory phosphorylation site, and therefore must be
      regulated by an alternative mechanism. The proline-rich sequence adjacent to the
      SH3 domain of Tec family kinases contains an SH3 ligand, potentially allowing a
      different intramolecular interaction. By using multidimensional nuclear magnetic
      resonance we have determined the structure of a fragment of Itk, confirming that
      these domains interact intramolecularly. Formation of this intramolecular SH3
      ligand complex prevents the Itk SH3 domain and proline-rich region from
      interacting with their respective protein ligands, Sam68 and Grb-2. We believe
      that this structure represents the first example of an intramolecular interaction
      between an SH3 domain and a proline-rich ligand, and has implications for the
      regulation of Tec family kinases.

PMID- 8985257
TI  - Quantitative measurement of autoantibodies to recombinant mitochondrial antigens
      in patients with primary biliary cirrhosis: relationship of levels of
      autoantibodies to disease progression.
AB  - We examined the clinical usefulness of measurements of antimitochondrial
      autoantibodies (AMA) in predicting disease progression in patients with primary
      biliary cirrhosis (PBC). We determined the relationships between AMA levels
      measured by indirect immunofluorescence (IF) and those measured by quantitative
      enzyme immunoassays (EIAs) using recombinant 2-oxo-acid dehydrogenase complex (2
      OADC) proteins and the Mayo Risk Score, an established indicator of disease
      progression in primary biliary cirrhosis (PBC). Results of tests for AMA by
      either method correlated weakly (r = .24 to .30) with disease progression as
      indicated by Mayo Risk Scores. The levels of AMA to 2-OADC proteins varied by
      more than 200-fold between patients but remained relatively constant over time in
      individual patients. Despite being positively correlated with Mayo Risk Score
      results, the levels of AMA to 2-OADC proteins were not useful for predicting
      disease progression in individual patients with PBC. In addition, we found no
      significant differences in the levels of autoantibodies to 2-OADC proteins among
      patients with different histological stages of disease. Our results show that
      measurements of AMA by IF or by quantitative EIA methods with recombinant 2-OADC
      proteins are not useful parameters for predicting disease progression in patients
      with PBC.

PMID- 8985258
TI  - Decreased anion exchanger 2 immunoreactivity in the liver of patients with
      primary biliary cirrhosis.
AB  - Chloride-bicarbonate anion exchanger 2 (AE2) is expressed in a variety of
      tissues, including the liver and salivary glands, where it may participate in the
      generation of hydroionic fluxes into secretions. We have previously reported
      decreased hepatic levels of AE2 messenger RNA in patients with primary biliary
      cirrhosis (PBC), a cholestatic condition frequently associated with
      pluriglandular exocrine failure. Here we investigated the expression of AE2
      protein in the liver of PBC patients. Using a monoclonal antibody against an AE2
      peptide, immunohistochemistry was performed on liver biopsy specimens from
      subjects with normal liver (n = 7), patients with PBC (n = 13), and patients with
      cirrhosis or cholestasis other than PBC (n = 17 and 11, respectively).
      Immunostaining was graded from 0 to 7, according to its intensity and
      distribution. AE2 immunoreactivity was observed in normal livers, as previously
      reported, and in many pathological liver biopsy specimens, being mainly
      restricted to canaliculi and the luminal membrane of terminal and interlobular
      bile ducts. Canalicular and ductular scores were significantly reduced in the PBC
      group compared with each control group (normal liver and cirrhosis or cholestasis
      other than PBC), whereas no differences in immunoreactivity scores were observed
      among control groups. When four patients with primary sclerosing cholangitis
      (PSC) were analyzed, they also differed from those with PBC. These results
      suggest that PBC is characterized by diminished expression of AE2 in the liver.
      Reduced levels of this transporter protein might be involved in the pathogenesis
      of cholestasis in PBC.

PMID- 8985259
TI  - Simultaneous determination of plasma mevalonate and 7alpha-hydroxy-4-cholesten-3
      one levels in hyperlipoproteinemia: convenient indices for estimating hepatic
      defects of cholesterol and bile acid syntheses and biliary cholesterol
      supersaturation.
AB  - The high prevalence of cholesterol gallstone disease in hypertriglyceridemic
      patients may be associated with frequent metabolic defects in cholesterol and
      bile acid syntheses and in the concomitant formation of bile supersaturated with
      cholesterol. This study had the two aims: 1) to assess whether the defects as
      well as the degree of biliary cholesterol supersaturation in patients with
      hyperlipoproteinemia (HLP) can be estimated by the simultaneous determination of
      plasma mevalonate (MVL) and 7alpha-hydroxy-4-cholesten-3-one (C4); and 2) to
      assess the possible application of an estimated cholesterol saturation index
      ([CSI]E) as a means of evaluating the clinical effects of simvastatin on biliary
      lipid composition. Biliary cholesterol supersaturation was observed in patients
      with both IIa and IV HLP types. Consistent with the high activity and steady
      state messenger RNA level of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA)
      reductase, plasma MVL was significantly higher in 86 patients with HLP (38 type
      IIa, 44.1 +/- 2.4 nmol/L and 48 type IV, 56.7 +/- 2.3; P < .01) than in 41
      normolipidemic subjects (34.2 +/- 1.5), closely correlating with the molar
      percentage of cholesterol in bile (r = .61, P = .0001; n = 86). On the other
      hand, consistent with the high activity and messenger RNA level of cholesterol
      7alpha-hydroxylase, plasma C4 was significantly higher in patients with HLP (type
      IIa, 28.8 +/- 2.3 nmol/L and type IV, 38.3 +/- 2.7; P < .01) than in
      normolipidemic subjects (17.4 +/- 1.5). Plasma C4 was closely correlated with
      plasma MVL (r = .40, P = .0001; n = 86), but was inversely correlated with the
      molar percentage of bile acids in bile (r = .49, P = .0001; n = 86). Assuming
      that cholesterol supersaturation in patients with HLP may be governed by both an
      enhanced cholesterol secretion (closely reflected by plasma MVL) and a decreased
      secretion of bile acids (closely reflected by plasma C4), the multivariate linear
      regression-analyses revealed that an index defined as estimated CSI ([CSI]E) (%)
      in patients with HLP was given by the following equation using plasma MVL and C4
      (nmol/L): [CSI]E = 1[MVL] + 0.7[C4] + 44.4. Biliary cholesterol supersaturation
      in patients treated with simvastatin improved in a manner parallel to the time
      course of decreases in plasma MVL and C4. The [CSI]E before and at the end of
      treatment were correlated with biliary CSI. These results indicate that defects
      of hepatic cholesterogenesis, and bile acid synthesis, and the degree of biliary
      cholesterol supersaturation in patients with HLP can be estimated exactly by the
      simultaneous determination of plasma MVL and C4; furthermore [CSI]E may be
      adopted for clinical use as a convenient index of biliary CSI.

PMID- 8985260
TI  - In situ nucleic acid hybridization of pyruvate dehydrogenase complex-E2 in
      primary biliary cirrhosis: pyruvate dehydrogenase complex-E2 messenger RNA is
      expressed in hepatocytes but not in biliary epithelium.
AB  - Pyruvate dehydrogenase-E2, or a cross-reactive molecule, has been shown by a
      variety of immunohistochemical methods to be present in increased amounts in
      biliary epithelial cells (BEC) in primary biliary cirrhosis (PBC). In this study,
      to further understand the nature of the immunoreactive molecule in BEC, we
      examined the expression of pyruvate dehydrogenase complex-E2 (PDC-E2) messenger
      RNA (mRNA) and PDC-E2 protein in sections of livers from patients and controls to
      help identify the molecule found in BEC. We performed in situ hybridization using
      an antisense probe against the major epitope of PDC-E2. The data were very
      striking and suggested that there was no increased production of PDC-E2 in BEC.
      For example, in livers from patients with PBC, PDC-E2 mRNA was found in
      periportal hepatocytes in 16 of 17 cases (94%). In contrast, interlobular bile
      ducts and septal bile ducts had detectable levels of PDC-E2 mRNA in only 1 of 17
      (6%) and 3 of 8 (38%) cases, respectively. Interestingly, proliferating bile
      ductules contained detectable levels of mRNA in 12 of 15 cases (80%). In control
      liver, periportal hepatocytes were positive in 15 of 17 cases (88%). Interlobular
      bile ducts, septal bile ducts, and proliferating bile ductules expressed mRNA
      signals in 4 of 17 (24%), 2 of 10 (20%), and 14 of 16 (88%), respectively. When
      formalin-fixed, paraffin-embedded sections were examined by immunohistochemical
      staining with anti-PDC-E2 monoclonal antibody (mAb) C355.1, the interlobular bile
      ducts showed typical aberrant apical staining in all 10 PBC cases, but 0 of 9
      liver controls. Periportal hepatocytes, proliferating bile ductules and
      infiltrating mononuclear cells stained with C355.1 but in a characteristic
      mitochondrial staining pattern. The presence of a PDC-E2-like molecule recognized
      by C355.1 is not reflected by the expression levels of PDC-E2 mRNA in the BEC of
      patients with PBC.

PMID- 8985261
TI  - Accumulation of multiple T-cell clonotypes in the liver of primary biliary
      cirrhosis.
AB  - The histological hallmark of primary biliary cirrhosis (PBC) is the destruction
      of the interlobular and septal bile ducts accompanied by a dense accumulation of
      lymphocytes; this constellation of features is termed chronic nonsuppurative
      destructive cholangitis. To analyze the T cells responsible for bile duct
      destruction, the T-cell receptor (TCR) Vbeta repertoire was studied in liver
      biopsy specimens, and also in peripheral blood lymphocytes (PBL) obtained from
      seven patients with PBC in the early stage (Scheuer's stage I or II). The
      complementary DNA (cDNA) of each TCR Vbeta1-20 chain was amplified by reverse
      transcription polymerase chain reaction (RT-PCR), and the PCR products were
      examined by single-strand conformation polymorphism (SSCP) analysis. On the RT
      PCR/SSCP analysis, a leukemic cell line, HPB-ALL, showed bands in TCR Vbeta 5.2
      and Vbeta 6, indicating clonal expansion with distinct TCR. In the PBL from
      healthy subjects, the PCR products were amplified from many TCR Vbeta and were
      shown as smears on SSCP, suggesting that PBL consist of diverse T-cell clones. In
      PBC, many TCR Vbeta products were amplified by RT-PCR in both liver tissues and
      PBL, and no biased expression of a particular Vbeta was observed. SSCP analysis
      revealed multiple bands in most Vbeta chains, suggesting the presence of selected
      but multiple T-cell clones. Both the number and types of Vbeta showing clonal
      expansion were heterogeneous in the PBC patients. A comparative RT-PCR SSCP
      analysis of each TCR Vbeta between tissue lymphocytes and PBL revealed the
      presence of some identical T-cell clones in both the PBC liver and the PBL. These
      results suggest that T cells infiltrating the liver in PBC consist of multiple
      clonotypes and that T-cell clones accumulated in the liver are also present in
      PBL.

PMID- 8985262
TI  - Biliary secretion of anionic polypeptide fraction is not coupled to that of
      phospholipids and cholesterol in rats.
AB  - Anionic polypeptide fraction (APF) is a phospholipid- and calcium-binding
      apoprotein present in animal and human bile, predominantly associated with
      cholesterol-phospholipid vesicles. In bile, the protein may play a physiological
      role in preventing precipitation of calcium salts. APF has also been suggested to
      be of regulatory importance in the process of biliary lipid secretion. The aim of
      the present study was to investigate whether the secretion rates of APF and that
      of biliary lipids are coupled, which would support a physiological role of APF in
      biliary lipid secretion. Biliary secretion rates of bile acids, phospholipids,
      and cholesterol were experimentally modulated in three different rat models.
      Secretion rates of APF were compared with that of bile acids, lipids, and with
      that of two other biliary proteins, the lysosomal protein beta-glucuronidase and
      apolipoprotein A-I (apo A-I). Model 1: diurnal variation in bile formation during
      chronic bile diversion; model 2: specific inhibition of biliary phospholipid and
      cholesterol, but not of bile acid secretion by infusion of the organic anion,
      sulfated lithocholyltaurine; model 3: acute interruption of the enterohepatic
      circulation in unanesthetized rats. The diurnal variation in bile formation
      involved a parallel increase of the biliary secretion rates of bile acids (+56 +/
      7%, mean +/- SD), phospholipids (+53 +/- 29%), cholesterol (+73 +/- 54%), and
      APF (+72 +/- 86%) during the night phase of the cycle. Infusion of sulfated
      lithocholyltaurine inhibited biliary phospholipid and cholesterol secretion (-78
      +/- 15%, and -54 +/- 25%, respectively), but did not affect biliary bile acid or
      APF secretion rate (-19 +/- 14%, and +12 +/- 107%, respectively). Within 4 hours
      after interruption of the enterohepatic circulation, bile secretion rates for
      bile acids (-92 +/- 3%), phospholipids (-74 +/- 13%), cholesterol (-64 +/- 8%),
      and APF (-58 +/- 24%) rapidly declined to a new steady-state level. Correlation
      analysis using the data from the three experimental models indicated that the
      biliary secretion rate of APF was independent from that of phospholipids,
      cholesterol, beta-glucuronidase, and, presumably, apolipoprotein A-I, and
      positively correlated to bile acid secretion rate and bile flow. The data from
      three experimental models indicate that the biliary secretion rates of APF and of
      phospholipids/cholesterol are not coupled and, therefore, do not support a direct
      physiological role of APF secretion in biliary lipid secretion. APF secretion
      into bile may, at least partially, be controlled by biliary bile acid secretion.

PMID- 8985264
TI  - The hyperventilation of cirrhosis: progesterone and estradiol effects.
AB  - Progesterone and estradiol are metabolized in the liver and are elevated in
      patients with cirrhosis. Progesterone stimulates ventilation by activating
      progesterone receptors in the central nervous system; estradiol may facilitate
      progesterone's actions by increasing progesterone receptors. This study evaluated
      whether progesterone and estradiol contribute to the respiratory alkalosis common
      in cirrhotic patients. Arterial blood gases and progesterone and estradiol levels
      were obtained in 50 patients with cirrhosis. Multiple linear regression revealed
      a statistically significant correlation between PaCO2 and progesterone and
      estradiol (r = .54, P < .05). Patients with severe hyperventilation (PaCO2 < or =
      30 mm Hg) had statistically higher levels of progesterone and estradiol than did
      patients with mild hyperventilation (30 < PaCO2 < or = 35) or normal ventilation
      (PaCO2 > 35) (P < .05). Although the progesterone levels were two orders of
      magnitude lower than those associated with hyperventilation in pregnant patients,
      the increased ventilatory effect may be because of the altered blood-brain
      barrier (BBB) present in cirrhotic patients. Progesterone and estradiol appear to
      contribute to the hyperventilation in cirrhotic patients.

PMID- 8985263
TI  - Cerebral abnormalities in patients with cirrhosis detected by proton magnetic
      resonance spectroscopy and magnetic resonance imaging.
AB  - Hepatic encephalopathy is a common problem in cirrhosis. The pathogenesis of this
      complication of advanced liver disease still remains unclear. Magnetic resonance
      spectroscopy was used to assess prospectively cerebral metabolism in 51 patients
      with histologically proven cirrhosis (Child-Pugh classes A, B, and C, 18, 18, and
      15, respectively) and 36 healthy volunteers. According to the results of
      psychometric tests, overt hepatic encephalopathy, subclinical encephalopathy, and
      no encephalopathy were found in 14, 21, and 16 patients, respectively.
      Myoinositol/creatine ratios in gray (.36 +/- .17) and white (.35 +/- .22) matter
      voxel were reduced significantly (P < .0001) in cirrhotic patients compared with
      healthy volunteers (gray matter, .51 +/- .11; white matter, .64 +/- .16). In
      addition, patients showed a significant reduction (P = .024) in white matter
      choline/creatine ratio (.77 +/- .27) compared with controls (.92 +/- .25), and
      glutamine/glutamate level was elevated in cirrhotic patients compared with
      controls (gray matter, P < .0001; white matter, P = .036). Changes in cerebral
      myoinositol and glutamine/glutamate levels correlated significantly with the
      severity of hepatic encephalopathy (P < .0001). However, these metabolic
      alterations were also detected in patients without hepatic encephalopathy (normal
      psychometric test results). N-acetyl aspartate/creatine ratios did not differ
      between patients and controls. Magnetic resonance imaging detected bright basal
      ganglia in 37 patients, which correlated significantly with portal-systemic
      shunting and elevation of glutamine/glutamate, but not with the degree of hepatic
      encephalopathy. In conclusion, magnetic resonance imaging and spectroscopy showed
      that alterations of cerebral metabolism are common in patients with cirrhosis,
      even without evidence of clinical or subclinical hepatic encephalopathy.

PMID- 8985265
TI  - Total volume paracentesis decreases variceal pressure, size, and variceal wall
      tension in cirrhotic patients.
AB  - It has been suggested that ascites is a risk factor for variceal bleeding in
      cirrhotic patients. However, no data of total volume paracentesis (TVP) effects
      on variceal hemodynamics has yet been published. The aim of this study was to
      investigate the effects of TVP on variceal pressure, size, and tension in
      cirrhotic patients. Before sclerotherapy, 18 cirrhotic patients with grade II
      esophageal varices were studied. The following measurements were performed on 12
      patients at basal condition and after TVP: inferior vena cava pressure,
      esophageal pressure (EP), and intravariceal pressure (IVP) by direct punction and
      variceal size at endoscopy. The same measurements were performed at basal
      condition and 1 hour later without TVP on the other 6 patients used as a control
      group. Variceal pressure gradient (VPG) and variceal wall tension (WT) were
      calculated. Paracentesis and intra-abdominal pressure were obtained with a direct
      punction. No demographic differences were observed between both groups.
      Paracentesis produced a significant reduction of IVP (from 25.6 +/- 2.4 to 17.9
      +/- 2.1 mm Hg, means +/- SEM, -30%, P < .05), VPG (from 16.6 +/- 2.4 to 10.8 +/-
      1.4 mm Hg, -35%, P < .05). TVP also reduced variceal size (from 9 +/- 0.3 to 5.6
      + 0.4 mm, -38%, P < .05) and WT (from 75.3 +/- 11.6 to 30 +/- 4.7 mm Hg. mm, 
      60%, P < .05). Intra-abdominal pressure decreased from 18 +/- 2.2 to 4 +/- 0.9 mm
      Hg (P < .05), and IVC decreased from 15.5 +/- 2.4 to 5.7 +/- 1.5 mm Hg (P < .05).
      No significant differences were observed in mean arterial pressure and heart
      rate. The mean ascitic fluid removed was 8 +/- 0.71 L. No significant difference
      between measurements was observed in the control group. Our results show that TVP
      significantly decreases variceal pressure and tension. These results suggest that
      ascites removal can be useful in the treatment of variceal bleeding in cirrhotic
      patients.

PMID- 8985266
TI  - Beta-adrenergic antagonists in the prevention of gastrointestinal rebleeding in
      patients with cirrhosis: a meta-analysis.
AB  - A meta-analysis of 12 selected randomized trials was performed to assess the
      efficacy of beta-blockers in the prevention of rebleeding and the effect on long
      term survival in patients with cirrhosis. Five end points were assessed:
      rebleeding, variceal rebleeding, death, death from bleeding, and adverse events.
      Analyses were performed according to the intention-to-treat method. For each end
      point, heterogeneity and treatment efficacy were assessed by the Der Simonian and
      Peto methods. When a significant difference was observed, sensitivity analyses
      were performed by successive stratifications according to treatment duration,
      cause of initial bleeding, use of placebo, type of beta-blocker, type of
      publication, certainty of randomization, severity of cirrhosis, interval between
      index bleed and randomization, and methodological quality. Beta-blockers
      significantly increased the mean percentage of patients free of rebleeding (21%
      mean improvement rate, CI 95%: 10%-32%, P < .001, relative risk 1.42), the mean
      percentage of patients free of variceal rebleeding (20% mean improvement rate, CI
      95%: 11%-28%, P < .001), the mean survival rate (5.4% mean improvement rate, CI
      95%: 0%-11%, P = .05, relative risk 1.27), the mean percentage of patients free
      of bleeding death (7.4%, CI 95%: 2%-13%, P < .01, relative risk 1.50). Five
      patients would need to be treated with beta-blockers to prevent one rebleeding
      episode, 14 treated to prevent one death, and 13 treated to prevent one death
      from bleeding. There was no significant heterogeneity among studies by both
      methods of analysis. In patients with esophageal varices, beta-blockers
      significantly increase the mean percentage of patients free of rebleeding and the
      mean survival rate at 2 years.

PMID- 8985267
TI  - Endoscopic variceal ligation is superior to combined ligation and sclerotherapy
      for esophageal varices: a multicenter prospective randomized trial.
AB  - Patients who have bled from varices remain at risk for rebleeding. There is
      interest in methods that would enable rapid eradication of varices. The present
      trial was designed to study whether combining ligation with sclerotherapy will
      allow quicker eradication of varices than either modality alone. Patients with
      bleeding esophageal varices were randomized into ligation or combination therapy
      groups. Patients in the ligation group were treated with endoscopic rubber band
      ligation alone. In combination group patients, each variceal column was ligated
      distally and 1 mL of ethanolamine was injected proximal to each ligated site.
      Subsequent treatment sessions were at 7- to 14-day intervals until varices were
      eradicated. The clinical and endoscopic characteristics of 25 patients in the
      ligation group were similar to those of 22 patients in the combination group.
      Follow-up was up to 30 months. Active bleeding was controlled in 100% of patients
      in the ligation group and 75% of those in combination group (P = NS). It took 3.3
      +/- .4 (range, 1-7) sessions to eradicate varices with ligation and 4.1 +/- .6 (1
      7) with combination therapy (P = NS). Survival (four deaths in ligation group, 8
      in combination group), rebleeding rate (25% vs. 36%), and varix recurrence (16%
      vs. 23%) also were similar. There were more complications with combination
      therapy, including deep ulcers (65% vs. 20%; P < .05); dysphagia (30% vs. 0%; P <
      .05), with three strictures requiring dilation; and pain (30% vs. 10%; P = NS).
      Our results show that sclerotherapy combined with ligation offers no benefit over
      ligation alone. The higher complication rate with combination therapy does not
      warrant this approach.

PMID- 8985268
TI  - Immune response to cyclin B1 in hepatocellular carcinoma.
AB  - Proteins expressed by plasmids encoding human cyclins and cyclin-dependent kinase
      2 (CDK2) were used as antigens in immunoblotting. Fifteen of 100 patients with
      hepatocellular carcinoma (HCC) were found to have autoantibodies reactive with
      cyclin B1 and with a 40-kd degradation product of cyclin B1-glutathione-S
      transferase (GST) fusion protein. Only one serum was found to react with cyclin A
      and another single serum with CDK2 but no antibodies were detected to cyclin D1
      and E. The basis for autoimmune responses to cyclin B1 in HCC are unknown at the
      present time but the possibilities might include aberrations in cyclin B1
      regulation leading to altered product or its expression which resulted in
      stimulation of immune reactions.

PMID- 8985269
TI  - Cytoprotection by fructose and other ketohexoses during bile salt-induced
      apoptosis of hepatocytes.
AB  - Toxic bile salts cause hepatocyte necrosis at high concentrations and apoptosis
      at lower concentrations. Although fructose prevents bile salt-induced necrosis,
      the effect of fructose on bile salt-induced apoptosis is unclear. Our aim was to
      determine if fructose also protects against bile salt-induced apoptosis. Fructose
      inhibited glycochenodeoxycholate (GCDC)-induced apoptosis in a concentration
      dependent manner with a maximum inhibition of 72% +/- 10% at 10 mmol/L. First, we
      determined if fructose inhibited apoptosis by decreasing adenosine triphosphate
      (ATP) and intracellular pH (pHi). Although fructose decreased ATP to <25% of
      basal values, oligomycin (an ATP synthase inhibitor) did not inhibit apoptosis
      despite decreasing ATP to similar values. Fructose (10 mmol/L) decreased
      intracellular pH (pHi) by 0.2 U. However, extracellular acidification (pH 6.8),
      which decreased hepatocyte pHi 0.35 U and is known to inhibit necrosis, actually
      potentiated apoptosis 1.6-fold. Fructose cytoprotection also could not be
      explained by induction of bcl-2 transcription or metal chelation. Because we
      could not attribute fructose cytoprotection to metabolic effects, alterations in
      the expression of bcl-2, or metal chelation, we next determined if the poorly
      metabolized ketohexoses, tagatose and sorbose, also inhibited apoptosis;
      unexpectedly, both ketohexoses inhibited apoptosis. Because bile salt-induced
      apoptosis and necrosis are inhibited by fructose, these data suggest that similar
      processes initiate bile salt-induced hepatocyte necrosis and apoptosis. In
      contrast, acidosis, which inhibits necrosis, potentiates apoptosis. Thus,
      ketohexose-sensitive pathways appear to initiate both bile salt-induced cell
      apoptosis and necrosis, whereas dissimilar, pH-sensitive, effector mechanisms
      execute these two different cell death processes.

PMID- 8985270
TI  - Patterns of recurrence after initial treatment in patients with small
      hepatocellular carcinoma.
AB  - To assess intrahepatic metastasis (IM) and multicentric occurrence (MO) after
      initial treatment of small hepatocellular carcinomas (HCC) < or = 2 cm in
      diameter, we performed clinical and pathological studies in 112 patients who
      underwent percutaneous ethanol injection therapy (PEIT) or hepatic resection for
      HCC from January 1985 to December 1994. Patients with intrahepatic recurrences
      were classified into two groups based on the type of recurrence: the IM group (n
      = 29, 50.9%) and the MO group (n = 28, 49.1%). Overall recurrence rates after
      initial treatment were 23.7% at 1 year, 64.5% at 3 years, and 76.1% at 5 years.
      In patients with IM, the majority of intrahepatic recurrences were observed
      within 3 years of initial treatment and the primary HCC lesions were closely
      related to the degree of tumor cell differentiation. Alternatively, intrahepatic
      recurrences occurred throughout the follow-up period in patients with MO, and the
      evidence of underlying liver disease (anti-HCV [antibody to hepatitis C virus]
      positive) and elevated serum alfa-fetoprotein (AFP) concentrations were closely
      associated with intrahepatic recurrence. Prognoses following additional treatment
      in MO group patients were superior to those in IM group patients. These results
      suggest that differentiation between IM and MO in patients with HCC is important
      for understanding the development and biological behavior of the tumor. That is,
      the early detection of intrahepatic recurrence and the institution of appropriate
      additional therapy (PEIT or hepatic resection) may prolong survival in patients
      with MO.

PMID- 8985271
TI  - Increased circulating transforming growth factor beta1 in a patient with giant
      hepatic hemangioma: possible contribution to an impaired immune function.
AB  - A patient, having a huge hepatic hemangioma, presented with decreases in the
      number of peripheral lymphocytes and in serum concentrations of gamma-globulin
      and immunoglobulin (Ig) G, and a negative purified protein derivatives skin test,
      indicating that the patient's immunity was impaired. The plasma concentration of
      transforming growth factor beta1 (TGF-beta1), a potent immunosuppressor, in the
      patient was markedly elevated (113 ng/mL, normal < 5). After the surgical removal
      of the tumor, the plasma TGF-beta1 concentration decreased, and the patient's
      immunity was restored to normal. Northern blot analysis showed an overexpression
      of the TGF-beta1 gene in the hemangioma tissue, while normal control liver tissue
      expressed undetectable levels of TGF-beta1 messenger RNA. These results suggest
      that the elevated levels of TGF-beta1 in the plasma were derived from the giant
      hemangioma tissue and may have contributed to the impaired immune function in the
      patient.

PMID- 8985272
TI  - Induction of hepatocyte growth factor activator messenger RNA in the liver
      following tissue injury and acute inflammation.
AB  - Hepatocyte growth factor activator (HGFA) is a serine protease that is
      responsible for localized activation of hepatocyte growth factor (HGF) in injured
      tissue. The activated HGF may be involved in regeneration of the injured tissue.
      HGFA is produced and secreted by the liver and circulates in the plasma as an
      inactive zymogen. In response to tissue injury, the HGFA zymogen is converted to
      the active form by limited proteolysis. In this study, we isolated a rat HGFA
      complementary DNA (cDNA) clone and analyzed the production of HGFA messenger RNA
      (mRNA) in response to tissue injury using this cDNA clone as a probe. The
      nucleotide sequence of the cDNA revealed that the amino acid sequences of rat and
      human HGFA showed a high degree of conservation in the regions of the
      characteristic domain structures, suggesting that rat and human HGFA are
      activated by a similar mechanism and have similar enzymatic activities in vivo.
      Tissue distribution analysis showed that the liver was the major site of rat HGFA
      mRNA synthesis. Moreover, the cells producing HGFA mRNA were identified as
      parenchymal liver cells. The level of HGFA mRNA increased in the liver after
      hepatotoxin or nephrotoxin treatment. This increase was also observed during
      acute inflammation induced by turpentine. These results suggest that the increase
      in production of HGFA mRNA in response to tissue injury is the result of an
      inflammatory response, and that HGFA is an acute phase protein.

PMID- 8985273
TI  - Hepatic injury during ketoconazole therapy in patients with onychomycosis: a
      controlled cohort study.
AB  - To evaluate the incidence, severity, and course of ketoconazole-associated
      hepatic injury, 211 patients with onychomycosis were randomized by a ratio of 2:1
      to receive either ketoconazole (137 patients) or griseofulvin (74 patients). All
      of them were seronegative for hepatitis B surface antigen (HBsAg) and anti
      hepatitis C virus (HCV) and had no biochemical abnormality before therapy. The
      two groups were comparable in age, sex, and pretherapy liver biochemical tests.
      Liver biochemical tests were followed up biweekly for 3 months, and then at
      monthly intervals during the remaining course of therapy. No biochemical
      abnormality or hepatic injury was found in patients during griseofulvin
      treatment. Of the patients treated with ketoconazole, 24 (17.5%; 95% confidence
      interval [CI], 11.1% to 23.9%) showed asymptomatic transaminase elevation.
      Ketoconazole was discontinued immediately after overt hepatitis developed in
      another 4 patients (2.9%; 95% CI, 0.1% to 5.7%) who did not succumb to hepatic
      decompensation. The abnormal biochemical changes in patients with overt hepatitis
      returned to normal after discontinuing ketoconazole. Elderly patients were more
      prone to develop overt hepatitis. In patients with asymptomatic liver injury, the
      abnormal biochemical changes gradually returned to normal despite continuing
      ketoconazole therapy. The results of this cohort study suggest that ketoconazole
      induced overt hepatitis is more common than previously believed and that
      transient subclinical injury is much more common than overt hepatitis. Therapy
      with ketoconazole may be continued with caution in the absence of symptoms and/or
      hyperbilirubinemia, but should be discontinued if overt hepatitis occurs.

PMID- 8985274
TI  - Excess weight risk factor for alcoholic liver disease.
AB  - Though the hepatotoxicity of ethanol has been established, only 8% to 20% of
      chronic alcoholics develop cirrhosis. The aim of this study was to assess whether
      being overweight is a risk factor for alcoholic liver disease. One thousand six
      hundred four alcoholic patients were studied. According to the liver biopsies,
      194 patients had a normal liver; 402 had steatosis without fibrosis; 281
      presented with fibrosis, with or without steatosis; 119 presented with acute
      alcoholic hepatitis (AAH) without cirrhosis; 232 indicated cirrhosis without AAH;
      and 179 presented with cirrhosis with AAH. One hundred ninety-seven patients had
      clinically obvious cirrhosis. In the study, five variables were studied as risk
      factors: age, sex, daily consumption of alcohol during the previous 5 years, the
      total duration of alcohol abuse, and tendency to be overweight (body mass index
      [BMI] > or = 25 in women and > or = 27 in men). The BMI was calculated according
      to the minimum weight over the 10 previous years. In the first stepwise logistic
      regression analysis, age, being overweight for at least 10 years, being of the
      female sex, and the total duration of alcohol abuse were independently correlated
      with the presence of cirrhosis. In the second analysis, female sex being
      overweight were the two independent risk factors of AAH. In the third analysis,
      being overweight for at least 10 years was the only independent risk factor of
      steatosis. These results show that the presence of excess weight for at least 10
      years is a risk factor for cirrhosis, AAH, and steatosis. Our results suggest
      that there is a possible potential for the metabolic effects of ethanol ingestion
      caused by excess weight in patients with alcoholic liver disease.

PMID- 8985275
TI  - Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol
      metabolizing enzymes in Chinese patients.
AB  - It is still not clear why some alcoholic patients acquire certain organ-specific
      complications of alcoholism whereas other alcoholic patients acquire different
      ones. As we know the liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase
      (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and
      ALDH2 loci and the 5'-flanking region of the P4502E1. The aim of this study was
      to investigate the differences between Chinese alcoholic patients with cirrhosis
      and acute pancreatitis by studying the genetic polymorphisms of ADH2, ADH3,
      ALDH2, and P4502E1. Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was performed
      using polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) methods on peripheral white blood cell DNA from 75 alcoholic cirrhotic
      patients, 48 acute alcoholic pancreatitis patients, 19 heavy drinkers without
      liver disease or pancreatitis, and 235 controls. The results showed that the
      frequencies of the alleles ADH2*1 and ALDH2*1 in the alcoholic cirrhotic patients
      were significantly higher than those in the nonalcoholic controls. In acute
      alcoholic pancreatitis patients, only the frequency of allele ALDH2*1, not ADH2*1
      was significantly higher than in the nonalcoholic controls. The allele frequency
      of ADH2*1 in acute pancreatitis patients was significantly lower (P < .01) than
      in alcoholic cirrhotic patients. The daily amount of alcohol consumption was
      significantly lower in patients with acute pancreatitis than in patients with
      cirrhosis (P < .0005). The genotype distributions of P4502E1, detected by RsaI
      and PstI, were not different among alcoholic cirrhotic patients, alcoholic
      pancreatitis patients, heavy drinker, and nonalcoholic controls. In conclusion,
      ALDH2*1 is the most important alcohol metabolizing gene affecting predisposition
      to alcoholism whereas the ADH2*2 gene may influence susceptibility to acute
      alcoholic pancreatitis. The patients with alcohol-induced cirrhosis and with
      alcohol-induced acute pancreatitis are of two different subpopulations.

PMID- 8985276
TI  - Hepatic amyloidosis: clinical appraisal in 77 patients.
AB  - The purpose of this study was to assess prognostic factors and survival in
      patients with liver involvement in immunoglobulin light-chain amyloidosis.
      Comparisons were made with other patients with immunoglobulin light-chain
      amyloidosis who did not have liver involvement. A total of 77 consecutively seen
      patients were evaluated: 19 had hepatic amyloidosis and 58 had amyloidosis
      without liver involvement. Eighteen of 19 patients with liver amyloidosis could
      be histologically diagnosed without needle biopsy of the liver. All but 2 had a
      detectable free light chain in the serum or urine, distinguishing this from other
      infiltrative liver processes. Patients with liver amyloid had significantly
      higher alkaline phosphatase levels and C-reactive protein levels compared with
      patients without hepatic amyloid. The majority of patients had extrahepatic
      involvement predominantly in the kidney (47%) or heart (42%). The presence of
      hyposplenism was not a good screening test for the presence of hepatic amyloid.
      Seven of 19 patients responded to chemotherapy with objective regressions of the
      clinical manifestations of renal, hepatic, or cardiac involvement. We conclude
      that the survival of patients with liver involvement in amyloidosis is no
      different than other patients with amyloidosis. This results from the high
      proportion of patients having associated renal or cardiac involvement. Most
      patients can be diagnosed without a liver biopsy when a monoclonal protein is
      found in the serum or urine. Serum albumin and C-reactive protein levels appear
      to distinguish patients with liver involvement from those without.

PMID- 8985277
TI  - Effect of nitric oxide on iron-mediated oxidative stress in primary rat
      hepatocyte culture.
AB  - An iron-mediated oxidative stress caused by an increase of the intracellular pool
      of low molecular weight complex of iron (LMWC) can be observed with iron
      overloading or ethanol metabolism. The aim of this study was to determine whether
      nitric oxide (NO) behaved as a pro-oxidant or an antioxidant in such an iron
      mediated oxidative stress in rat hepatocytes. The cells were set up in primary
      cultures and incubated with lipopolysaccharide (LPS) and gamma-interferon (IFN)
      for 18 hours to induce NO synthase and to trigger NO production. Then 20
      micromol/L iron or 50 mmol/L ethanol were added. Oxidative stress was evaluated
      by measuring lipoperoxidation using two markers: malondialdehyde (MDA) and
      conjugated dienes. Simultaneously, NO production was followed by the quantitation
      of nitrites in the culture medium, dinitrosyl iron complexes (DNICs) and
      mononitrosyl iron complexes (MNICs) in intact hepatocytes. DNIC and MNIC,
      evaluated by electron paramagnetic resonance (EPR), corresponded to NO bound to
      iron-containing molecules and to free NO, respectively. In cultures preincubated
      with LPS and IFN before iron or ethanol addition, a net decrease of lipid
      peroxidation induced by either NO, iron, or ethanol was noted. Moreover, an
      elevation of iron-bound NO and a decrease of free NO were observed in these
      cultures compared with the cultures incubated with only LPS and IFN. These data
      support the idea that there is a relationship between the changes of NO pool and
      the inhibition of oxidative stress. In addition, using N(G)-monomethyl-L-arginine
      (L-NMMA), a NO synthase inhibitor, NO was shown to be involved in the inhibition
      of oxidative stress induced by iron or ethanol. Addition of the chelator of LMWC
      iron, deferiprone, was followed by the inhibition of the increase of iron-bound
      NO and the reincrease of lipid peroxidation extent, which was as high as in
      cultures incubated only with LPS and IFN. Thus LMWC iron appeared to be involved
      also in the inhibition of oxidative stress induced by NO. All the results favor
      the conclusion that NO acts as an antioxidant in iron-mediated oxidative stress
      in rat hepatocytes. NO reacted with LMWC iron to form inactive iron complexes
      unable to induce oxidative stress in rat hepatocytes. Thus NO played a critical
      role in protecting the liver from oxidative stress.

PMID- 8985278
TI  - Mechanisms of alcohol impairment of recovery from mechanically denuded areas made
      within cultured rat hepatocytes.
AB  - The effect of ethanol on the ability of a denuded hepatocyte cell surface to
      recover is unknown. We therefore determined the effect of ethanol on the rate of
      renewal of mechanical wounds made in near-confluent monolayers of primary
      cultures of rat hepatocytes. We found that ethanol exerted a dose-dependent
      effect to impair rat hepatocyte recovery and that at least 12 hours of exposure
      to ethanol was required to induce this impairment. The effect of ethanol to
      impair recovery of denuded areas of epithelium was not seen in two established
      renal tubular epithelial cell lines. Ethanol impairment of rat hepatocyte
      recovery could be blocked by an alcohol dehydrogenase inhibitor (4-methyl
      pyrazole) and potentiated by an inhibitor of aldehyde dehydrogenase (pargyline).
      The effect of ethanol to inhibit rat hepatocyte recovery of denuded areas was not
      associated with any change in hepatocyte cell surface expression of the beta1
      integrin subunit as determined by flow cytometry. These results suggest that
      acetaldehyde is responsible for ethanol inhibition of hepatocyte recovery from
      mechanical injury and that this impairment occurs independent of cell surface
      expression of the beta1 integrin subunit.

PMID- 8985279
TI  - Induction of early-immediate genes by tumor necrosis factor alpha contribute to
      liver repair following chemical-induced hepatotoxicity.
AB  - We and others have shown that tumor necrosis factor alpha (TNF-alpha) expression
      is increased in the livers of experimental animals following exposure to the
      chemical hepatotoxin, carbon tetrachloride (CCl4). Because TNF-alpha is involved
      in mediating inflammatory responses, its elevated expression is presumed to be
      associated with potentiating hepatotoxicity and/or aiding in liver repair
      processes. To study the role of TNF-alpha in chemical-induced hepatotoxicity,
      mice were administered neutralizing antibodies to TNF-alpha before administration
      of low, but hepatotoxic, doses of CCl4. Antibody treatment prevented CCl4
      mediated increases in early-immediate gene expression associated with liver
      regeneration, including expression of c-jun and c-fos proto-oncogenes, as well as
      DNA binding of the activator protein-1 (AP-1) nuclear transcription factor.
      Hepatocyte proliferation following CCl4 treatment was also reduced in anti-TNF
      alpha antibody-treated mice, as evidenced by a lack of proliferating cell nuclear
      antigen (PCNA) staining. Antibody treatment slightly delayed liver repair
      processes, as evidenced by extending the period in which plasma liver enzyme
      levels were increased and hepatocellular necrosis could be observed. Consistent
      with the above observations, injection of recombinant TNF-alpha into control mice
      induced rapid expression of c-jun and c-fos proto-oncogenes. Taken together,
      these results indicate that TNF-alpha positively modulates liver recovery
      following CCl4 exposure presumably by stimulating early-immediate genes involved
      in hepatic mitogenesis, a phenomenon also observed following partial hepatectomy.

PMID- 8985280
TI  - 4-hydroxynonenal levels are enhanced in fetal liver mitochondria by in utero
      ethanol exposure.
AB  - Lipid peroxidation has been implicated in ethanol-induced liver injury and
      observed in fetal liver and brain after maternal ethanol consumption with
      mitochondria being the target organelles. This process generates a highly
      reactive and toxic product, 4-hydroxynonenal (HNE). In the present study, HNE
      levels and metabolism were assessed in mitochondria of fetal and maternal liver
      after in vivo ethanol exposure. Female Sprague-Dawley rats received five doses of
      ethanol (4 g/kg orally at 12-hour intervals) and were killed on day 19 of
      gestation. The results showed that HNE levels were enhanced in hepatic
      mitochondria of fetal rats exposed to ethanol, far in excess of that in adult
      liver mitochondria. Measurement of HNE metabolism showed that fetal mitochondria
      had a lower capacity for HNE catabolism than adult mitochondria. In adult
      mitochondria, HNE could be metabolized by nicotine adenine dinucleotide-dependent
      oxidation, reduced glutathione conjugation, and reduced nicotine adenine
      dinucleotide-dependent reduction, whereas in fetal liver only the former two
      pathways were active, but to a lesser degree than in adult mitochondria. On the
      other hand, mitochondria from fetal liver showed a higher production of HNE when
      oxidative stress was induced with t-butyl hydroperoxide. Prior in vivo ethanol
      exposure further potentiated HNE formation in t-butyl hydroperoxide-stimulated
      fetal liver mitochondria, but not in adult mitochondria. These findings indicate
      that increased levels of HNE in fetal liver mitochondria after maternal ethanol
      consumption reflect a higher susceptibility to HNE formation in addition to a
      lesser capacity to metabolize it. The enhanced accumulation of this toxic
      aldehyde may contribute to oxidative damage observed in fetal tissues after in
      utero ethanol exposure.

PMID- 8985281
TI  - Carnitine metabolism in patients with chronic liver disease.
AB  - Carnitine metabolism was studied in 79 patients with chronic liver disease,
      including 22 patients with noncirrhotic liver disease and 57 patients with
      different types of cirrhosis (22 patients with hepatitis B- or C-associated
      cirrhosis, 15 patients with alcohol-induced cirrhosis, 15 patients with primary
      biliary cirrhosis [PBC], and 5 patients with cryptogenic cirrhosis), and compared
      with 28 control subjects. In comparison with control subjects, patients with
      noncirrhotic liver disease showed no change in the plasma carnitine pool, whereas
      patients with cirrhosis had a 29% increase in the long-chain acylcarnitine
      concentration. Analysis of subgroups of patients with cirrhosis showed that
      patients with alcohol-induced cirrhosis had an increase in the total plasma
      carnitine concentration (67.8 +/- 29.5 vs. 55.2 +/- 9.9 micromol/L in control
      subjects), resulting from increases in both the short-chain and long-chain
      acylcarnitine concentration. In this group of patients, the acylcarnitine
      concentrations showed a close correlation with the total carnitine concentration,
      and the total carnitine concentration with the serum bilirubin concentration.
      Urinary excretion of carnitine was not different between patients with
      noncirrhotic or cirrhotic liver disease and control patients. However, patients
      with PBC showed an increased urinary excretion of total carnitine (52.5 +/- 40.0
      vs. 28.0 +/- 16.7 micromol carnitine/mmol creatinine), resulting from an increase
      in the fractional excretion of both free carnitine and short-chain acylcarnitine.
      The current studies show that patients with cirrhosis are normally not carnitine
      deficient. Patients with alcohol-induced cirrhosis have increased plasma
      carnitine concentrations, which may result from increased carnitine biosynthesis
      because of increased skeletal muscle protein turnover. The increase in the
      fractional carnitine excretion in patients with primary biliary cirrhosis may
      result from competition of bile acids and/or bilirubin with tubular carnitine
      reabsorption and/or from a reduced activity of the carnitine transporter located
      in the proximal tubule.

PMID- 8985282
TI  - The synthesis rates of total liver protein and plasma albumin determined
      simultaneously in vivo in humans.
AB  - Although the metabolism of liver-derived plasma proteins such as albumin has been
      extensively studied, human hepatic protein synthesis as a whole has not been well
      characterized, because a reproducible model for obtaining human liver tissue has
      not been available. In this study, the fractional synthesis rates of total liver
      protein and albumin in vivo were determined simultaneously in nine subjects
      undergoing elective laparoscopic cholecystectomy. L-[2H5]phenylalanine (45 mg/kg
      body wt) was administered for 10 minutes intravenously. Blood samples were
      collected at regular intervals for 90 minutes and a liver biopsy specimen was
      taken at 35 +/- 7 minutes. The enrichments of plasma free phenylalanine, plasma
      albumin, and total liver protein were measured with gas chromatography mass
      spectrometry (GC-MS). The fractional synthesis rate (FSR) of total liver protein
      was 24.7 +/- 3.1 %/d (mean +/- SD), and that of albumin was 5.9 +/-1.2%/d. The
      amount of albumin synthesized per day (absolute synthesis rate, ASR) was 109 +/-
      21 mg/kg body wt. No correlation between FSR of total liver protein and ASR of
      albumin was found. It is concluded that the technique of obtaining liver tissue
      specimens during laparoscopic surgery may serve as a human in vivo model to study
      total liver protein synthesis. The fractional synthesis rate of total liver
      proteins (stationary and exported), equals approximately 25% of the liver protein
      content daily. Within the range of values of this study, the absolute synthesis
      rate of albumin was not correlated to the fractional synthesis rate of total
      liver protein.

PMID- 8985283
TI  - The frequency of hemochromatosis-associated alleles is increased in British
      patients with sporadic porphyria cutanea tarda.
AB  - The cause of the hepatic siderosis and iron overload that is common in porphyria
      cutanea tarda (PCT) is uncertain. Heterozygosity for genetic hemochromatosis has
      been supported by some studies of the association between the HLA-A3 antigen and
      porphyria cutanea tarda but not by others. The hemochromatosis gene is now
      believed to be located telomeric to HLA-A3 and close to the DNA microsatellite
      marker D6S1260. We have used this and other microsatellite markers, which
      together define an ancestral haplotype that is strongly linked to
      hemochromatosis, to reinvestigate the relationship between these disorders in 41
      British patients with sporadic PCT. Fifteen patients carried the hemochromatosis
      associated alleles D6S265-1 and D6S105-8. Four of these were homozygous for the
      ancestral haplotype D6S265-1 : D6S105-8: D6S1260-4. We estimate that
      approximately 37% of British patients with sporadic PCT carry at least one
      hemochromatosis gene compared with 10% of the general population.

PMID- 8985284
TI  - The relationship between iron overload, clinical symptoms, and age in 410
      patients with genetic hemochromatosis.
AB  - The aim of this study was to investigate the relationship between iron overload,
      age, and clinical symptoms in genetic hemochromatosis. The relationship was
      studied between clinical symptoms and liver iron concentration, serum ferritin,
      and iron removed in a retrospective study of 410 homozygotes diagnosed using
      strict criteria. No significant relationship was found between liver iron
      concentration, iron removed by venesection, and serum ferritin level with age.
      The prevalence of cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue
      increased as liver iron concentration increased. The most common presentations at
      diagnosis were fatigue or as an incidental finding in all age groups. Twenty
      seven percent of patients (110 of 410) had no clinical symptoms of
      hemochromatosis. Iron accumulation is highly variable in patients with genetic
      hemochromatosis. The significant relationship between liver iron concentration
      and cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue confirms the
      importance of iron toxicity in the pathogenesis of hepatic and extrahepatic
      disease. The nonspecific nature of the presenting features in patients and the
      presence of significant clinical symptoms in patients discovered through family
      investigations underscore the importance of family and population screening for
      hemochromatosis.

PMID- 8985285
TI  - Repolarization of hepatocytes in culture.
AB  - We have evaluated the biochemical, morphological, and functional redevelopment of
      polarity in freshly isolated hepatocytes cultured using a double layer collagen
      gel sandwich technique. Western blot analysis showed increased cellular levels of
      the cell adhesion protein uvomorulin as cultured hepatocytes repolarized.
      Immunofluorescence studies using antibodies against domain-specific membrane
      proteins showed polarity as early as 48 hours, although the pattern of the
      polymeric Immunoglobulin-A receptor (pIgA-R) differed from in vivo liver.
      Electron microscopy showed developing bile canaliculi at 1 day. However, the
      functional presence of tight junctions was absent at 1 day, but present at 5
      days. We further showed functional polarity to be present at 4 days by
      documenting the ability of cultured hepatocytes to metabolize and excrete
      fluorescein diacetate into visible bile canaliculi. We conclude that hepatocytes
      cultured appropriately develop morphological and functional polarity. Hepatocyte
      culture is therefore a useful tool for the study of mechanisms responsible for
      the development of polarized function.

PMID- 8985286
TI  - Prednisone withdrawal late after adult liver transplantation reduces diabetes,
      hypertension, and hypercholesterolemia without causing graft loss.
AB  - We prospectively withdrew prednisone in 28 adult patients who had stable graft
      function more than 2 years after orthotopic liver transplantation (OLTx) and had
      been on 5 mg/d prednisone for at least 6 months. Prednisone was decreased from 5
      mg/d to 2.5 mg/d for 1 month then stopped completely. Cyclosporine monotherapy
      was maintained at a level of approximately 200 ng/mL (TDX). Nineteen patients had
      prednisone withdrawn without complications. Four (14.2%) had modest elevations in
      liver function tests (two biopsy proven mild rejections and two were not
      biopsied). These four were treated with methylprednisolone boluses and then
      withdrawal of steroids again. Prednisone was restarted in five patients because
      of generalized fatigue and body aches (n = 4) and colitis (n = 1). Steroids later
      were successfully withdrawn in two of these patients. After prednisone
      withdrawal, three of five insulin-dependent diabetic patients were able to
      discontinue insulin therapy and their glycosylated hemoglobin levels improved.
      Four of fourteen hypertensive patients were able to discontinue antihypertensive
      medicines. Mean serum cholesterol decreased from 222.6 +/- 43.3 to 188.3 +/- 33.3
      mg/dL (P < .001). The number of patients with serum cholesterol levels > 220
      mg/dL decreased from 13 to 4. A control group of 24 patients maintained on 5 mg/d
      prednisone at least 2 years after liver transplantation also was studied. In this
      group during the study period, no diabetic became normoglycemic, no patient
      decreased their antihypertensive medicine, and the mean serum cholesterol levels
      did not change significantly. We conclude that prednisone withdrawal using
      cyclosporine monotherapy late after liver transplantation does not lead to graft
      loss and decreases the prevalence of diabetes, hypertension, and
      hypercholesterolemia. Symptoms occurring during withdrawal may be minimized by
      earlier or slower tapering.

PMID- 8985287
TI  - Changes in adipose tissue composition in malnourished patients before and after
      liver transplantation: a carbon-13 magnetic resonance spectroscopy and gas-liquid
      chromatography study.
AB  - We investigated adipose tissue fatty acid composition in 22 moderately to
      severely malnourished patients with cirrhosis and in 22 healthy volunteers by in
      vivo carbon-13 magnetic resonance spectroscopy (MRS). Gas-liquid chromatography
      (GLC) of adipose tissue samples was also performed in 11 of the patients and in 4
      volunteers. In vivo 13C magnetic resonance spectra were obtained from the
      subcutaneous adipose tissue before and after eight weeks following orthotopic
      liver transplantation (OLT). Adipose tissue biopsy samples were obtained for GLC
      analysis at the time of transplantation in the patients and at inguinal hernia
      repair in the 4 volunteers. No significant differences were found in the
      subcutaneous adipose tissue total-saturated, -polyunsaturated or -monounsaturated
      fatty acid composition between patients and healthy volunteers by in vivo 13C
      MRS. GLC analysis of adipose tissue samples confirmed that total levels of
      saturated, poly-, and monounsaturated fatty acids remained the same but revealed
      significant differences in levels of individual fatty acids, particularly n-3
      fatty acids (total n-3, cirrhotics: .84% +/- .07% vs. controls: 1.36% +/- .13%, P
      < .01). Eight weeks following transplantation, recipients showed a considerable
      increase in body mass (pretransplantation: 59.3 +/- 3.2 vs. posttransplantation:
      63.2 +/- 3 kg, P < .01). 13C MRS revealed a significant increase in saturated
      fatty acids (pretransplantation: 21.6 +/- 2.8 vs. posttransplantation: 25.5% +/-
      1.2%, P < .05) and a significant decrease in unsaturated fatty acids. The
      application of noninvasive MRS techniques may be important to identify the
      differential uptake of fats, examining both specific fatty acids and different
      body fat compartments. In the future, this may be useful in optimizing the
      dietary management of severely malnourished patients with chronic liver disease
      before liver transplantation.

PMID- 8985288
TI  - Predictive value of intraoperative biopsies and liver function tests for
      preservation injury in orthotopic liver transplantation.
AB  - Eighty liver allografts were studied to determine the predictive value of
      intraoperative biopsies and postoperative liver function tests for the
      development of preservation injury (PI). Peak transaminase (aspartate
      transaminase [AST] and alanine transaminase [ALT]) and prothrombin time (PT)
      values achieved by each patient during postoperative days (POD) 1 through 7 were
      determined. PI in day 0 preperfusion biopsies (0Pre) (obtained immediately before
      implantation) and postperfusion biopsies (0Post) (obtained immediately after
      revascularization) was categorized by histological criteria as present or absent.
      PI in biopsies taken during POD 2 through 14 was histologically graded as either
      moderate-to-severe, mild, or absent. Of the 80 allografts, 8 were omitted because
      of primary nonfunction or postoperative complications. 0Pre and 0Post biopsies
      were available on 25 of 72 (35%) and 69 of 72 (96%) allografts, respectively.
      Only 2 (8%) of the 0Pre biopsies showed histological PI compared with 48 (70%) of
      the 0Post biopsies. Fifty-nine patients were biopsied between POD 2 through 14.
      Of these, 15, 28, and 16 patients developed moderate-to-severe, mild, or no
      evidence of PI, respectively. The presence of PI in the 0Post biopsy strongly
      correlated with the development of PI during POD 2 through 14 (P < .0005). Peak
      AST and ALT values in patients with moderate-to-severe PI on POD 2 through 14
      were significantly elevated compared with those patients with either mild (P =
      .01 and .03) or no PI (P = .02 and .006). Because of extensive overlap in AST and
      ALT values between the three groups, however, transaminase values were not useful
      in predicting the presence or absence of PI in the individual case. The
      development of PI during POD 2 through 14 correlated with advanced donor age (P =
      .06) but was unassociated with 0Pre biopsy findings, cold ischemia time, or peak
      PT values. We conclude that the 0Post biopsy is a valuable tool for the
      prediction of subsequent PI in the early postoperative period. In contrast, 0Pre
      biopsy findings and peak AST and ALT values are not useful in the assessment of
      PI.

PMID- 8985289
TI  - Persistent cytomegalovirus in liver allografts with chronic rejection.
AB  - Cytomegalovirus (CMV) infection is one of the suggested risk factors for chronic
      allograft rejection. Clinical and experimental studies have shown that CMV is
      somehow implicated in rejection mechanisms and in the generation of graft
      arteriosclerosis, characteristic of chronic rejection. In liver transplantation,
      there is also evidence of an association between CMV and vanishing bile duct
      syndrome (VBDS), which is characteristic of chronic liver allograft rejection. In
      this study, the role of posttransplant CMV infection and of acute rejection in
      the patients with irreversible, histologically confirmed chronic liver rejection
      with VBDS and vasculopathy was analyzed. Ten of 200 (5%) consecutive liver
      transplants were lost due to chronic rejection, from between 5 and 28 months from
      transplantation. In these 10 patients, acute rejections were frequent, and nine
      of ten patients had at least one episode of rejection early after
      transplantation. All patients (10 of 10) had a history of CMV infection usually
      following acute rejection. To investigate the role of CMV in chronic rejection,
      nine available removed grafts were examined for the presence of the CMV genome by
      DNA-hybridization in situ using a biotinylated CMV-DNA probe. Persistent CMV-DNA
      was found in all of those available grafts with chronic rejection. CMV-DNA was
      strongly expressed in the remaining bile ducts and moderately expressed in the
      endothelial cells of the vascular structures, the CMV positivity of hepatocytes
      varied from graft to graft. Thus, persistent CMV genome was found in those
      structures that are the major targets of the chronic rejection process in the
      liver. These findings support the previous suggestion of an association between
      CMV and chronic allograft rejection.

PMID- 8985292
TI  - Lack of correlation between hepatitis C virus genotypes and clinical course of
      hepatitis C virus-related cirrhosis.
AB  - The influence of the hepatitis C virus (HCV)-genotype on liver disease severity
      was evaluated in 429 consecutive patients with chronic hepatitis C, including 109
      with cirrhosis who were followed up prospectively, allowing for the assessment of
      the role of the HCV-genotype on disease outcome and on the development of
      hepatocellular carcinoma (HCC). HCV-1 was detected in 147 (46%) patients without
      cirrhosis and in 47 (43%) with cirrhosis (P: not significant), being mainly HCV
      1b. HCV-2 was found in 103 (32%) cases without cirrhosis and in 30 (27.5) with
      cirrhosis (P: not significant), being mainly HCV-2a. HCV-3 was detected in 32
      (10%) patients without cirrhosis and in 2 (2%) with cirrhosis (P < 0.005).
      Infection with more than one genotype (HCV-1/HCV-2 and HCV-1/HCV-3) was observed
      only in cirrhotic patients (6 of 109; 5.5%). During a mean follow-up of 67 +/- 22
      months, 21 (19%) patients with cirrhosis showed worsening in Child's stage, 5
      (4.5%) underwent liver transplantation, 23 (21%) developed HCC, and 24 (22%) died
      of complication of liver disease; the overall incidence of at least one of these
      events was 38.5%. By the Kaplan-Meier method and log-rank test, the cumulative
      probability of developing each or at least one of the above events did not differ
      in relation to the genotype of infecting HCV, apart from patients with mixed
      genotype infection who showed a significantly higher incidence of death (P <
      .05). These data indicate that HCV-genotypes do not have a significant effect on
      the severity and outcome of liver disease in patients with chronic HCV-infection.
      Patients with cirrhosis who are also infected by HCV-1 and HCV-2 had a similar
      prognosis and progression to HCC, while patients infected by more than one
      genotype showed the most unfavorable course of disease.

PMID- 8985291
TI  - Long-term outcome of hepatitis C virus infection after liver transplantation.
AB  - We analyzed the long-term clinical course of 71 patients with RNA-positive
      hepatitis C virus (HCV) infection after liver transplantation. Patients with
      reinfection after transplantation for HCV-related liver disease, or de novo
      infection at transplantation were followed for up to 12 years. Cumulative
      survival for patients with HCV infection at 2, 5, and 10 years after
      transplantation was 67%, 62%, and 62%, respectively. It was not significantly
      different from that in patients transplanted for other nonmalignant diseases
      without HCV infection. The main factor determining long-term survival was the
      presence or absence of hepatocellular carcinoma (HCC) at transplantation. The 5
      year survival rate for HCV patients with or without HCC was 35% versus 73%,
      respectively (P < .05). No deaths because of viral hepatitis of the graft were
      observed. Deaths in the first year after transplantation were caused by
      infectious complications, cardiovascular problems, or rejection; deaths after
      more than 12 months were exclusively because of recurrence of HCC. Biochemical
      and histological evidence of hepatitis was found in the majority of the patients,
      only 16% had normal alanine aminotransferase (ALT) values throughout. Twenty-two
      percent of patients complained of symptoms, with hepatitis C being the cause in
      82% of these. Two patients lost their HCV-RNA for prolonged, ongoing periods of
      time. The severity of the posttransplantation hepatitis was unrelated to age,
      sex, severity of liver disease before transplantation, cold ischemic time of the
      graft, duration of the operation, transfusions, the number of rejection episodes,
      or the long-term immunosuppressive regime. Only initial short-term therapy with
      interleukin 2 (IL2) receptor antibodies adversely influenced inflammatory
      activity. Viral genotype did not influence the course of the graft hepatitis in
      our series. Histology showed inflammation in 88% of the biopsies and signs of
      fibrosis in 24%. Mean ALT values correlated with inflammation but not with
      fibrosis in the biopsies. Porto-portal bridging was observed in six patients, one
      patient developed cirrhosis within 2 years after orthotopic liver transplantation
      (OLT). We conclude that chronic hepatitis develops in the majority of patients
      with HCV infection after liver transplantation. Carrier states without
      significant laboratory abnormalities are observed in approximately 16%,
      biochemical abnormalities without symptoms are seen in 60%, and symptomatic
      disease develops in a quarter of the patients. The disease course closely
      resembles that seen in nontransplanted hepatitis C patients. It is generally mild
      but little over 10% of patients develop signs of fibrosis of the graft during the
      first decade.

PMID- 8985290
TI  - Graft and systemic disease in long-term survivors of liver transplantation.
AB  - In this clinicopathological study, we have examined the prevalence of biochemical
      and histological graft abnormalities in 116 patients who have lived for longer
      than five years since orthotopic liver transplantation (mean, 8.4 years [range,
      5.2-19.5 years]). In each patient, the protocol biopsy was carried out in
      addition to full clinical, biochemical, and immunological evaluation. The renal
      function was preserved in most patients (mean creatinine, 86 micromol/L [0.95
      mg%]) with only 35% showing any degree of impairment, and only one patient with
      pretransplant renal failure required dialysis. Forty one (35%) of the patients
      had normal biochemical liver function tests (LFTs); 19 of these patients had
      histologic abnormalities. Of the remaining 75 patients with abnormal LFTs, 65
      were found to have histological abnormalities on liver biopsy. Some of the 84
      patients with an abnormal histology had more than one finding but were placed
      into 6 categories according to the main change as follows: chronic hepatitis in
      27; primary biliary cirrhosis-like changes in 8; cholangitis in 15; structural
      anomalies in 26; chronic rejection in 2; mild acute cellular rejection in 1; and
      miscellaneous in 5. The recurrence of B, C, or autoimmune hepatitis accounted for
      14 cases of chronic hepatitis, whereas, in 13 cases, no cause could be detected.
      The latter cases included 8 patients who had liver transplants for primary
      biliary cirrhosis (PBC), leaving suboptimally treated rejection or disease
      recurrence as possible causes. Characteristic histological features of PBC were
      observed in 8 additional cases that had liver transplantations for this disease.
      Of the 26 cases with structural anomalies, various types of occlusive
      vasculopathy were detected during pre- or posttransplantation in 12 cases. All
      but one of these were maintained on azathioprine, the only possible etiological
      factor in the 14 other cases, 5 of whom showed stabilization or clinical and
      histological improvement following withdrawal of the drug. De-novo malignancy was
      seen in 3.4% of cases, causing mortality in only one patient to date. This study
      demonstrates an unexpectedly high prevalence of histological abnormalities that
      is found often in the presence of normal biochemical liver-function in liver
      grafts of long-term survivors. Although graft loss at this time is rare, protocol
      liver biopsies at 5 years, and thereafter at 2-year intervals, may allow for
      earlier beneficial therapeutic intervention.

PMID- 8985293
TI  - Detection by ligase chain reaction of precore mutant of hepatitis B virus.
AB  - The clinical diagnosis of infection with the most common precore mutant of
      hepatitis B virus (HBV), that with a point mutation from guanine to adenine at
      nucleotide 83 in the precore region, is important because the disease may
      progress rapidly despite interferon therapy. A practical method to detect this
      mutant is needed. With the ligase chain reaction (LCR), target DNA sequences can
      be amplified and single base mutations can be detected. We tried to detect mutant
      HBV by the LCR alone, but the limit of detection (10(9) copies per tube) was too
      high. To increase the sensitivity, we used the LCR on DNA already amplified by
      the polymerase chain reaction (PCR), and tested serum samples from 23 subjects
      with chronic HBV infection for mutant and wild-type HBV. As few as 10(2) copies
      per tube could be detected. The results corresponded with the results of
      nucleotide sequencing for 22 of the 23 patients. The ratio of clones of mutant
      and total viruses was estimated for each individual by PCR-coupled LCR.
      Seroconversion could be identified earlier in the illness by an increase in this
      ratio than by the decrease in HBeAg. We also tested serum samples from 11
      patients with acute liver failure by PCR-coupled LCR. Mutant HBV was detected at
      a low ratio in all 4 patients with acute self-limited hepatitis (AH). Wild-type
      HBV coexisted with mutant HBV in 6 of 7 patients with fulminant hepatitis (FH),
      and the mean ratio of mutant to total HBV was significantly higher than that in
      AH. PCR-coupled LCR could be used to detect mutant HBV and to estimate the ratio
      of mutant to total viruses.

PMID- 8985294
TI  - Liver transplantation in Asian patients with chronic hepatitis B.
AB  - It has been suggested that Asian patients have reduced survival after liver
      transplantation because of greater recurrence of hepatitis B virus (HBV). We
      analyzed the outcome of Asian and non-Asian patients receiving transplants for
      chronic hepatitis B between May 1988 and March 1994. Baseline Child-Pugh score
      and United Network for Organ Sharing (UNOS) status, HBV recurrence, and survival
      were compared between the two groups. All but one patient received variable doses
      of hepatitis B immune globulin. Mean follow-up of surviving patients was 28
      months (range, 3-71 months). Fifteen Asians and 20 non-Asians underwent
      transplantation. Six of 15 Asians (40%) and 4 of 20 non-Asians (20%) died during
      the study period. Although Asians had a lower 1-year survival than non-Asians
      (59% for Asians and 94% for non-Asians), the 5-year actuarial survival was not
      different (59% and 57% for Asians and non-Asians, respectively). The causes of
      death in 5 of 6 Asians were factors other than recurrent hepatitis B, and 4 of 5
      deaths occurred within 60 days after transplantation. Eighty percent of Asian
      patients were Child-Pugh class C at referral, compared with 50% of non-Asians,
      and Asians were more likely to be status 1 at transplantation (40% vs. 10%; P <
      .05). By contrast, all four deaths in non-Asians occurred late and were secondary
      to recurrent HBV infection. Of patients surviving more than 60 days after
      transplantation, 7 of 11 Asians (64%) and 10 of 20 non-Asians (50%) developed
      recurrent HBV infection (NS). Late mortality attributable to HBV recurrence was
      lower but not significantly different in Asians (1 of 7 [14%]) than in non-Asians
      (4 of 10 [40%]). In summary, HBV recurrence and late HBV-related mortality in
      Asians and non-Asians is similar after liver transplantation for chronic
      hepatitis B. Late referral and more advanced chronic liver disease at the time of
      transplantation probably account for the lower 1-year survival of Asians after
      liver transplantation.

PMID- 8985295
TI  - Presence of antibodies to the hepatitis B surface antigen is associated with an
      excess risk for hepatocellular carcinoma among non-Asians in Los Angeles County,
      California.
AB  - Hepatocellular carcinoma (HCC) exhibits a more than 50-fold variation in
      incidence worldwide. High-risk regions include East Asia and sub-Saharan Africa,
      while non-Asians in the United States constitute a low-risk population. We
      assessed 111 cases of histologically confirmed HCC and 128 community control
      subjects among non-Asians of Los Angeles County for the presence in serum of
      hepatitis B surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies
      to the hepatitis B core antigen (anti-HBc), HBV DNA, and antibodies to the
      hepatitis C virus (anti-HCV). Anti-HCV positivity was significantly associated
      with a 12.6-fold increase in HCC risk (95% confidence limits = 4.7, 33.6). As
      expected, the presence of serum HBsAg and the presence of anti-HBc in the absence
      of anti-HBs were both positively associated with the risk of HCC. But most
      interestingly, among our study subjects, the presence of anti-HBs in the absence
      of HBsAg and HBV DNA (indicative of a resolved infection) was significantly
      related to a 4.7-fold increased risk for HCC (95% confidence limits = 2.2, 9.4).
      Overall, any serological evidence of prior HBV exposure was associated with a 9.4
      fold elevation in HCC risk (95% confidence limits = 4.7, 18.7). The data also
      demonstrate a synergistic effect of HBV and HCV infections on the risk of HCC. We
      estimate that about 55% of HCC cases occurring in non-Asians of Los Angeles can
      be attributed to infection by the hepatitis B and/or C viruses.

PMID- 8985296
TI  - Chronic viral hepatitis induced by hepatitis C but not hepatitis B virus
      infection correlates with increased liver angiogenesis.
AB  - Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections lead to
      cirrhosis and increase the risk for the development of hepatocellular carcinoma
      (HCC). Angiogenesis is an essential step in oncogenesis and contributes to tumor
      progression in adult organs; however, to what extent angiogenesis occurs in the
      liver during chronic viral hepatitis has not been studied. Ninety-nine matched
      patients affected by chronic hepatitis due to either HBV or HCV were studied
      together with 13 controls (5 patients were affected by familial
      hyperbilirubinemia with normal liver histology; 6 patients with stage II primary
      biliary cirrhosis; and 2 patients with pseudo inflammatory tumor). Microvessel
      density was assessed in liver biopsies by immunostaining using two different
      antibodies against endothelial cell antigens, QB-END/10 and Factor VIII. In
      addition, the liver homogenates and sera of HCV- or HBV-positive patients and
      controls were tested for their capacity to stimulate the migration and
      proliferation of freshly isolated human endothelial cells in vitro. Evidence of
      angiogenesis was significantly more frequent in HCV-positive patients compared
      with HBV-infected subjects or controls (74% vs. 39% vs. 8%) (chi2 = 20.78; P <
      .0001) (HCV+ vs. HBV+ vs. controls). The degree of microvessel density was also
      higher in HCV- than in HBV-positive patients or controls (chi2 = 12.28; P <
      .005). In addition, HCV-positive sera and liver homogenates stimulated a higher
      migration and proliferation of human endothelial cells in vitro compared with HBV
      positive or control sera and liver homogenates. These observations indicate that
      angiogenesis is particularly linked to HCV infection, suggesting a possible
      contribution to HCV-related liver oncogenesis.

PMID- 8985297
TI  - Nucleic acid sequence analysis of the precore region of hepatitis B virus from
      sera of southern African black adult carriers of the virus.
AB  - Our purpose was to ascertain if mutations of the precore region of the hepatitis
      B virus genome, in particular the 1896 stop codon mutation, are responsible for
      the 95% hepatitis B e antigen (HBeAg)-negativity rate in southern African black
      adult carriers. Hepatitis B virus (HBV) DNA was extracted from the serum of 57
      asymptomatic carriers (42 HBeAg-negative; 15 HBeAg-positive), the precore region
      was amplified using the polymerase chain reaction (PCR), and sequenced. Six
      carriers (14.6%) had mutations known to prevent HBeAg synthesis: 4 involved the
      precore initiation codon (1814), and one created a stop codon at 1874. The 1896
      mutation occurred alone in one carrier only (2.4%). The infrequency of the 1896
      mutation can be explained by the high prevalence (70%) of the adw subtype in the
      carriers studied. Inter alia, adw differs from ayw in that codon 15 is comprised
      of CCC instead of CCT. The presence of C instead of T in position 1858 precludes
      the G-to-A mutation at 1896 because the coexistence of these two mutations would
      destabilize the stem-loop structure of the RNA encapsidation signal, a finding
      confirmed by our observation that the CCC polymorphism and the 1896 mutation were
      mutually exclusive. Ten HBeAg-negative carriers (24%) had a missense mutation at
      position 1862 in the bulge of the RNA encapsidation signal, which may possibly
      affect HBeAg expression by interfering with either priming of reverse
      transcription or signal peptide cleavage. We conclude that the 1896 stop codon
      mutation accounts for a minority only of HBeAg-negative black carriers. A
      missense mutation in the bulge of the encapsidation signal may contribute to
      HBeAg negativity.

PMID- 8985298
TI  - Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis
      B surface antigen carriers: a placebo-controlled trial.
AB  - Lamivudine is a novel 2',3'-dideoxy cytosine analogue that has potent inhibitory
      effects on hepatitis B virus replication in vitro and in vivo. We performed a
      single-blind, placebo-controlled study to assess its effectiveness and safety in
      Chinese hepatitis B surface antigen (HBsAg) carriers. Forty-two Chinese HBsAg
      carriers were randomized to receive placebo (6 patients) or lamivudine orally in
      dosages of 25 mg, 100 mg, or 300 mg daily (12 patients for each dosage). The drug
      was given for 4 weeks. The patients were closely monitored clinically,
      biochemically, and serologically up to 4 weeks after drug treatment. All 36
      patients receiving lamivudine had a decrease in hepatitis B virus (HBV) DNA
      values of >90% (P < .001 compared with placebo). Although 25 mg of lamivudine was
      slightly less effective than 100 mg (P = .011) and 300 mg (P = .005), it still
      induced 94% suppression of HBV DNA after the fourth week of therapy. HBV DNA
      values returned to pretreatment levels within 4 weeks of cessation of therapy.
      There was no change in the hepatitis B e antigen status or in aminotransferase
      levels. No serious adverse events were observed. In conclusion, a 4-week course
      of lamivudine was safe and effective in suppression of HBV DNA in Chinese HBsAg
      carriers. The suppression was >90% but reversible. Studies with long-term
      lamivudine administration should be performed to determine if prolonged
      suppression of HBV DNA can be achieved.

PMID- 8985299
TI  - Hepatic venous pressure measurement: an old test as a new prognostic marker in
      cirrhosis?

PMID- 8985300
TI  - Can a vitamin prevent hepatocellular carcinoma?

PMID- 8985301
TI  - Hepatocyte lineages: of clones, streams, patches, and nodules in the liver.

PMID- 8985302
TI  - Chemokines and liver inflammation: the battle between pro- and anti-inflammatory
      mediators.

PMID- 8985303
TI  - Risk of colon cancer in patients with ulcerative colitis is potentiated by the
      presence of primary sclerosing cholangitis.

PMID- 8985304
TI  - Transjugular intrahepatic portosystemic shunt for refractory ascites: shunt
      diameter-optimizing risks and benefits.

PMID- 8985305
TI  - tau-Interferon: pregnancy recognition signal in ruminants.

PMID- 8985306
TI  - Biology of the mesangial cell in glomerulonephritis--role of cytokines.
AB  - The mesangial cell occupies a central position in the genesis of the pertubations
      occurring during the pathogenesis of glomerulonephritis. In vitro studies have
      shown that this cell is a metabolically active cell producing a variety of
      cytokines which act as autocoids; such cytokines are also liberated by the
      monocytes/macrophages which infiltrate the glomerulus in nephritis. This review
      summarizes the evidence for the participation of these cytokines in animal models
      of nephritis and in human renal disease, focusing on the roles of basic
      fibroblast growth factor, platelet-derived growth factor, transforming growth
      factor-beta, colony-stimulating factor-beta, tumor necrosis factor, interleukin
      1, and interleukin-6.

PMID- 8985307
TI  - Interleukin-6-type cytokines in vivo: regulated bioavailability.
AB  - Investigators have traditionally thought of the class of inflammation- and injury
      associated cytokines in large part as "free" entities in the peripheral
      circulation. In the case of interleukin-6 (IL-6), the cytokine can be found in
      blood in complexes of molecular mass 400-500, 150-200, and 25-35 kDa in
      association with binding proteins that can include soluble IL-6 receptor (sIL
      6R), anti-IL-6, and anti-sIL-6R IgG, and others. Sustained high levels of
      different particular IL-6 complexes are observed in the human circulation in
      cancer patients subjected to particular active anticancer immunotherapy regimens.
      In the "chaperoned" state, circulating IL-6 complexes display differential
      immunoreactivity in different ELISAs and possess differential biological activity
      as assayed ex vivo. The discovery of "chaperoned" circulating IL-6 in humans
      points to a new level of modulation of cytokine function, that of regulated
      bioavailability of IL-6 in vivo.

PMID- 8985308
TI  - The relevance of opioids and opioid receptors on immunocompetence and immune
      homeostasis.
AB  - Since the previous review on the role of opioids in the immune system, numerous
      investigative teams have contributed to the growing pool of information
      illustrating the tangible relationship between opioids and immune function,
      particularly as this association pertains to bacterial and viral pathogens. In
      addition, the recent cloning of both neural- and immune-derived opioid receptors
      will ultimately facilitate the identification of molecular events that are
      responsible for the immunomodulatory effects that are mediated by receptor
      ligation. Specifically, the administration of opioids in vivo can potentially
      affect the immune system either through direct interaction with receptors on the
      effector cells or indirectly, through the ligation of receptors found within the
      central nervous system. This indirect routing is hypothesized to involve
      secondary pathways including the hypothalamic pituitary adrenal (HPA) axis and
      the sympathetic nervous system ultimately resulting in immunomodulation.
      Consequently, a portion of this review addresses the recent data on leukocyte
      derived opioid receptors and the potential immunoregulatory role relative to
      opiold receptors found within the central nervous system. In addition, recent
      observations on the effects of opioids and immunocompetence is reviewed from both
      a molecular and cellular perspective. Finally, the consequence of opioid exposure
      on the competence of the host immune system to microbial pathogens is summarized.

PMID- 8985309
TI  - Effect of acetazolamide and melittin on polarization of the frog gastric mucosa
      proton pump.
AB  - We have shown that polarization of an electrogenic H+/K+ ATPase pump located in
      the secretory (luminal) membrane of the frog gastric mucosa is the major factor
      contributing to the change in open circuit potential difference (OCPD) induced by
      voltage clamping. This transmucosal polarization was markedly reduced by H2
      blockers famotidine and cimetidine, and by the H+/K+-ATPase inhibitors omeprazole
      and SCH 28080. SCN-, a nonspecific H+ secretion inhibitor, did not affect the
      polarization. In the present experiments, the effects of two other inhibitors of
      H+ secretion were examined, namely, acetazolamide (AA), a carbonic anhydrase
      inhibitor, and melittin (MEL), an inhibitor of the H+/K+-ATPase enzyme. When AA
      10(-3) M or MEL 10(-5) M was added to the nutrient solution, H+ secretion was
      completely inhibited. While MEL markedly reduced the polarization induced by
      voltage clamp, AA did not affect the polarization. These data support the concept
      that MEL directly affects the electrogenic H+/K+-ATPase pump while the inhibition
      of H+ secretion by AA is by an indirect mechanism. The data further support the
      electrogenicity of the H+/K+-ATPase.

PMID- 8985310
TI  - Effects of age on beta adrenergic subtype activation of adenylyl cyclase in brown
      adipose tissue.
AB  - Thermogenesis in brown adipose tissue (BAT) is believed to be mediated mainly by
      beta3 adrenergic receptors. We previously demonstrated that the specific beta3
      adrenergic agonist CGP-12177 increases whole body oxygen consumption and BAT GDP
      binding to a greater extent in young than in senescent rats. In contrast, the
      forskolin-induced increases were maintained with age, suggesting that early
      events in beta3 adrenergic signal transduction are impaired with age. To
      investigate whether beta1 or beta3 adrenergic function is decreased with age, we
      assessed beta1 and beta3 adrenergic receptor mRNA levels and the ability of beta1
      and beta3 adrenergic receptors to activate adenylyl cyclase in BAT membranes from
      4- and 24-month-old F-344 rats. Both beta1 and beta3 adrenergic receptor mRNA
      levels decreased by 50% with age. Adenylyl cyclase stimulated by the nonspecific
      agonist, isoproterenol, and by the specific beta3 agonist, BRL 37344, also
      declined by 50% with age, whereas glucagon stimulation decreased by more than
      70%. The isoproterenol-stimulated adenylyl cyclase activation curves were
      resolved by two-site regression analysis to determine the contribution of beta1
      and beta3 adrenergic receptors. The Vmax for both beta1 and beta3 adrenergic
      receptors decreased by 50% with age. However, stimulation of adenylyl cyclase by
      NaF and forskolin was also diminished by the same amount as beta adrenergic
      stimulation, suggesting that the activation with age may be limited by the amount
      of adenylyl cyclase catalytic unit rather than by receptor number. These data
      suggest both beta1 and beta3 adrenergic receptors and adenylyl cyclase catalytic
      units are deficient with age in rodent BAT.

PMID- 8985311
TI  - Neonatal androgenization potentiates the inhibitory effects of blood withdrawal
      on ovulation in the rat.
AB  - Rats treated on Day 5 of life with testosterone propionate (TP) were tested for
      their ovulatory response to pregnant mare's serum gonadotropin (PMSG) on the 30th
      day of life with and without cardiac puncture under ketamine/xylazine anesthesia.
      TP without cardiac puncture in doses of 0.625, 1.25, or 2.5 microg did not
      inhibit ovulation, but 5.0 microg of TP inhibited ovulation in 15 of 16 rats.
      When cardiac puncture was performed at 1900 hr in rats not given TP, seven of
      eight ovulated on Day 33. However, none of the rats that received either 1.25 or
      2.5 microg of TP ovulated after cardiac puncture at 1900 hr, and only one of
      seven given the 0.625-microg dose ovulated. Thus, the stress of bleeding greatly
      enhanced the inhibitory effect of otherwise ineffective doses of TP. The
      preovulatory luteinizing hormone (LH) surge was delayed and diminished by
      neonatal TP in a dose-related manner in animals from which blood was drawn from a
      previously inserted catheter. When blood drawn from similarly TP-treated animals
      by cardiac puncture, serum levels of LH were further reduced. Progesterone, given
      at 1100 hr on Day 32, was capable of partially overcoming the inhibitory effects
      of the combined treatments on both ovulation and serum LH levels at all but the
      highest dose of TP tested (5.0 microg). We conclude that neonatal exposure to
      androgen sensitizes rats to ovulation-inhibiting factors, such as bleeding, in a
      manner which appears to delay as well as inhibit the preovulatory release of LH.
      Such early exposure to androgen, therefore, may determine the susceptibility of
      individuals to reproductive failure in adult life.

PMID- 8985312
TI  - Ribosomal protein synthesis in 16 and 19 day gestation fetuses of hypothyroid
      mothers.
AB  - Thyroid hormones are transported across the placenta. Thyroid hormone receptors
      are present in the midgestation rat fetus and fetal tissues selectively
      accumulate thyroid hormones prior to the onset of fetal thyroid function. It has
      not been demonstrated adequately that maternal thyroid hormones are essential for
      early fetal physiologic functions and neurological development. The present study
      compares the effects of maternal thyroid hormone versus fetal thyroid hormone on
      the regulation of rRNA and ribosomal protein synthesis in the developing fetus.
      This was accomplished by first comparing 16-day gestation (just prior to the
      onset of fetal thyroid function) fetuses of control and hypothyroid mothers. Then
      19-day gestation (fetal thyroids are functional) fetuses of control and
      hypothyroid mothers were compared as development of fetal thyroid function lags
      in hypothyroid mothers. Rats made hypothyroid (Tx) by radiothyroidectomy were
      given replacement doses of thyroxine (T4) until the day that they were placed
      with a male for mating. Control, Tx and growth hormone (GH)-treated Tx dams and
      their fetuses were sacrificed on either the 16th or 19th day of gestation.
      Ribosomes (r) were isolated from placentas and from fetal brains and livers and
      rRNA, total 14C-leucine incorporation, and 14C-leucine incorporation into
      ribosomal protein per microgram of rRNA were determined. On the 16th day of
      gestation, prior to the onset of fetal thyroid function, all three of the above
      metabolic parameters were reduced significantly below control levels in the
      placentas of Tx rats and in the brains and livers of their fetuses. This was true
      also for the fetal brains and livers of GH-treated Tx mothers. Development of
      fetal thyroid function lags in the Tx mother. rRNA, total 14C-leucine
      incorporation, and 14C-leucine incorporation into ribosomal protein per microgram
      of rRNA continue to be significantly depressed in these fetal tissues and
      placentas of Tx rats on the 19th day of gestation. In fact, brain protein
      synthesis falls further behind in fetuses of Tx dams at this gestational age when
      compared with control fetal brains. These data support the hypothesis that
      maternal thyroid hormones are important, by at least midgestation, for normal
      fetal physiologic development and support the concept that appropriate maturation
      of the fetal pituitary-thyroid plays a role in fetal brain protein synthesis and
      therefore neurological development.

PMID- 8985313
TI  - Elevated levels of albumin in soleus and diaphragm muscles of mdx mice.
AB  - Muscle damage is often associated with an influx of extracellular fluid
      containing albumin into the muscle. Muscles affected by muscular dystrophy
      undergo severe muscle damage; therefore, the hypothesis was tested that muscles
      of dystrophic (mdx) mice contain elevated levels of albumin. Albumin levels in
      diaphragm (DIA) and soleus (SOL) muscles of control and mdx mice were measured at
      3 months and 1 year of age. Albumin in mdx DIA at 1 year of age was twice that of
      control. In mdx SOL at 1 year of age albumin was increased 25% compared with
      control. The increase in albumin correlates well with the decline in function in
      mdx DIA and SOL muscles. Electron microscopy of muscles suggests that albumin is
      co-localized with transverse tubules of muscle fibers and thus may be mainly
      located in extracellular fluid. We conclude that albumin is elevated in muscles
      affected by muscular dystrophy and suggest that this may be of clinical
      importance in view of substances bound to albumin under physiological conditions.

PMID- 8985314
TI  - Effect of 5-alpha dihydrotestosterone on T-cell proliferation of the female
      nonobese diabetic mouse.
AB  - Nonobese diabetic (NOD) mice develop type I diabetes spontaneously and have been
      utilized as a model for human autoimmune insulin-dependent diabetes. The disease
      is caused by the destruction of insulin-producing beta cells in the pancreatic
      islet of Langerhans by infiltrating inflammatory cells, which are primarily T
      lymphocytes. The incidence of diabetes in NOD mice is increased in females
      compared with males, suggesting that sex steroid hormones play an important role
      in the development of the disease. We therefore investigated the effect of a male
      steroid, 5-alpha-dihydrotestosterone (5DHT), on disease development, T-cell
      phenotype, T-cell proliferation, and cytokine profiles in this model. None of the
      mice that received 5DHT for 120 days (n = 7) developed insulitis, whereas all
      control mice (n = 8) developed the disease. The percentage of CD4+ T cells in
      peripheral blood mononuclear cells was markedly decreased in the 5DHT-treated
      females compared with those in controls (37.1 +/- 4.8 vs 51.3 +/- 9.3, P < 0.02),
      whereas no significant differences in the percentage of CD8+ T cells were
      observed between treated and control female mice. Results of a syngeneic mixed
      lymphocyte reaction (SMLR) also suggested that T cells are major target cells of
      5DHT administration. An increased expression of IL-4 mRNA, representing T helper
      2 (Th2) T cells, was observed in the SMLR. On the basis of these results, a
      systemic administration of 5DHT appears to have direct effects on the expansion
      of Th2 cell populations with subsequent restoration of normal immune responses.

PMID- 8985315
TI  - Influence of diet on the induction of experimental autoimmune thyroid disease.
AB  - Immunization of CBA/J mice with thryoglobulin (Tg) emulsified in complete
      Freund's adjuvant induces experimental thyroiditis (EAT), a well-characterized
      model of Hashimoto's disease. Recent studies have suggested that dietary factors
      play a role in the modulation of the immune response and that diet can have a
      profound effect on the induction of autoimmune diseases. In this study, we
      examined the influence of diet on autoimmune thyroiditis in mice. EAT was induced
      in mice fed ad libitum one of the three diets, a standard maintenance chow (Agway
      H1000), Purina 5020 Breeding Chow, and Purina 5010 Autoclavable (unautoclaved)
      Diet. Tg-immunized mice fed the Agway 1000 diet were found to be resistant to the
      development of autoimmune thyroid disease, with only 4 out of 25 mice developing
      mild thyroiditis. In contrast, 16 out of 25 mice fed the Purina 5010 diet
      developed moderate to severe thyroiditis. Mice fed the 5020 diet were partly
      susceptible: 7 out of 25 developed a mild to moderate thyroiditis. Histologic
      examination of thyroid glands of diseased mice fed the 5010 and 5020 diets showed
      marked lymphocytic infiltration with destruction of follicles, compared with mice
      fed the Agway diet, the latter showing only mild infiltration with preservation
      of thyroid follicles. Titers of antibody to Tg did not differ among the groups,
      and there was no significant difference in the IgG isotype subclass usage. The
      results demonstrate that diet can markedly affect the severity of autoimmune
      disease in the EAT model. In contrast, diet has little effect on the humoral
      autoimmune response in this system. These results implicate diet as a factor in
      the severity of cell-mediated autoimmune destruction and suggest that dietary
      modification could decrease pathology in some forms of autoimmune disease.

PMID- 8985316
TI  - Host range phenotype induced by mutations in the internal ribosomal entry site of
      poliovirus RNA.
AB  - Most poliovirus strains infect only primates. The host range (HR) of poliovirus
      is thought to be primarily determined by a cell surface molecule that functions
      as poliovirus receptor (PVR), since it has been shown that transgenic mice are
      made poliovirus sensitive by introducing the human PVR gene into the genome. The
      relative levels of neurovirulence of polioviruses tested in these transgenic mice
      were shown to correlate well with the levels tested in monkeys (H. Horie et al.,
      J. Virol. 68:681-688, 1994). Mutants of the virulent Mahoney strain of poliovirus
      have been generated by disruption of nucleotides 128 to 134, at stem-loop II
      within the 5' noncoding region, and four of these mutants multiplicated well in
      human HeLa cells but poorly in mouse TgSVA cells that had been established from
      the kidney of the poliovirus-sensitive transgenic mouse. Neurovirulence tests
      using the two animal models revealed that these mutants were strongly attenuated
      only in tests with the mouse model and were therefore HR mutants. The virus
      infection cycle in TgSVA cells was restricted by an internal ribosomal entry site
      (IRES)-dependent initiation process of translation. Viral protein synthesis and
      the associated block of cellular protein synthesis were not observed in TgSVA
      cells infected with three of four HR mutants and was evident at only a low level
      in the remaining mutant. The mutant RNAs were functional in a cell-free protein
      synthesis system from HeLa cells but not in those from TgSVA and mouse
      neuroblastoma NS20Y cells. These results suggest that host factor(s) affecting
      IRES-dependent translation of poliovirus differ between human and mouse cells and
      that the mutant IRES constructs detect species differences in such host
      factor(s). The IRES could potentially be a host range determinant for poliovirus
      infection.

PMID- 8985317
TI  - Characterization of pal-1, a common proviral insertion site in murine leukemia
      virus-induced lymphomas of c-myc and Pim-1 transgenic mice.
AB  - Insertional mutagenesis with Moloney murine leukemia virus (MoMLV) in c-myc and
      Pim-1 transgenic mice permits the identification of oncogenes that collaborate
      with the transgenes in lymphomagenesis. The recently identified common insertion
      site pal-1, in MoMLV-induced lymphomas, is located in a region in which several
      independent integration clusters are found: eis-1, gfi-1, and evi-5. Proviral
      insertions of MoMLV in the different integration clusters upregulate the
      transcriptional activity of the Gfi-1 gene, which is located within the pal-1
      locus. The eis-1/pal-1/gfi-1/evi-5 locus serves as a target for MoMLV proviral
      insertions in pre-B-cell lymphomas of Emu-myc transgenic mice (20%) and in T-cell
      lymphomas of H-2K-myc (75%) and Emu-pim-1 (93%) transgenic mice. Many tumors
      overexpress both Gfi-1 as well as Myc and Pim gene family members, indicating
      that Gfi-1 collaborates with Myc and Pim in lymphomagenesis. Proviral
      integrations in the previously identified insertion site bmi-1 are, however,
      mutually exclusive with integrations in the eis-1/pal-1/gfi-1/evi-5 locus. This
      finding suggests that Bmi-1 and Gfi-1 belong to the same complementation group in
      lymphoid transformation.

PMID- 8985318
TI  - Adaptability in herpesviruses: glycoprotein D-independent infectivity of
      pseudorabies virus.
AB  - Initial contact between herpesviruses and host cells is mediated by virion
      envelope glycoproteins which bind to cellular receptors. In several
      alphaherpesviruses, the nonessential glycoprotein gC has been found to interact
      with cell surface proteoglycans, whereas the essential glycoprotein gD is
      involved in stable secondary attachment. In addition, gD is necessary for
      penetration, which involves fusion between virion envelope and cellular
      cytoplasmic membrane. As opposed to other alphaherpesvirus gD homologs,
      pseudorabies virus (PrV) gD is not required for direct viral cell-to-cell spread.
      Therefore, gD- PrV can be passaged in noncomplementing cells by cocultivating
      infected and noninfected cells. Whereas infectivity was found to be strictly cell
      associated in early passages, repeated passaging resulted in the appearance of
      infectivity in the supernatant, finally reaching titers as high as 10(7) PFU/ml
      (PrV gD- Pass). Filtration experiments indicated that this infectivity was not
      due to the presence of infected cells, and the absence of gD was verified by
      Southern and Western blotting and by virus neutralization. Infection of bovine
      kidney cells constitutively expressing PrV gD interfered with the infectivity of
      wild-type PrV but did not inhibit that of PrV gD- Pass. Similar results were
      obtained after passaging of a second PrV mutant, PrV-376, which in addition to gD
      also lacks gG, gI, and gE. Penetration assays demonstrated that PrV gD- Pass
      entered cells much more slowly than wild-type PrV. In summary, our data
      demonstrate the existence of a gD-independent mode of initiation of infection in
      PrV and indicate that the essential function(s) that gD performs in wild-type PrV
      infection can be compensated for after passaging. Therefore, regarding the
      requirement for gD, PrV seems to be intermediate between herpes simplex virus
      type 1, in which gD is necessary for penetration and cell-to-cell spread, and
      varicella-zoster virus (VZV), which lacks a gD gene. Our data show that the
      relevance of an essential protein can change under selective pressure and thus
      demonstrate a way in which VZV could have evolved from a PrV-like ancestor.

PMID- 8985319
TI  - From essential to beneficial: glycoprotein D loses importance for replication of
      bovine herpesvirus 1 in cell culture.
AB  - Glycoprotein D (gD) of bovine herpesvirus 1 (BHV-1) has been shown to be an
      essential component of virions involved in virus entry. gD expression in infected
      cells is also required for direct cell-to-cell spread. Therefore, BHV-1 gD
      functions are identical in these aspects to those of herpes simplex virus 1 (HSV
      1) gD. In contrast, the gD homolog of pseudorabies virus (PrV), although
      essential for penetration, is not necessary for direct cell-to-cell spread.
      Cocultivation of cells infected with phenotypically gD-complemented gD- mutant
      BHV-1/80-221 with noncomplementing cells resulted in the isolation of the cell-to
      cell-spreading gD-negative mutant ctcs+BHV-1/80-221, which was present in the gD
      null BIV-1 stocks. ctcs+BHV-1/80-221 could be propagated only by mixing infected
      with uninfected cells, and virions released into the culture medium were
      noninfectious. Marker rescue experiments revealed that a single point mutation in
      the first position of codon 450 of the glycoprotein H open reading frame,
      resulting in a glycine-to-tryptophan exchange, enabled complementation of the gD
      function for cell-to-cell spread. After about 40 continuous passages of ctcs+BHV
      1/80-221-infected cells with noninfected cells, the plaque morphology in the
      cultures started to change from roundish to comet shaped. Cells from such plaques
      produced infectious gD- virus, named gD-infBHV-1, which entered cells much more
      slowly than wild-type BHV-1. In contrast, integration of the gD gene into the
      genomes of gD-infBHV-1 and ctcs+BHV-1/80-221 resulted in recombinants with
      accelerated penetration in comparison to wild-type virions. In summary, our
      results demonstrate that under selective conditions, the function of BHV-1 gD for
      direct cell-to-cell spread and entry into cells can be compensated for by
      mutations in other viral (glyco)proteins, leading to the hypothesis that gD is
      involved in formation of penetration-mediating complexes in the viral envelope of
      which gH is a component. Together with results for PrV, varicella-zoster virus,
      which lacks a gD homolog, and Marek's disease virus, whose gD homolog is not
      essential for infectivity, our data may open new insights into the evolution of
      alphaherpesviruses.

PMID- 8985320
TI  - In vivo and in vitro phosphorylation of rotavirus NSP5 correlates with its
      localization in viroplasms.
AB  - NSP5 (NS26), the product of rotavirus gene 11, is a phosphoprotein whose role in
      the virus replication cycle is unknown. To gain further insight into its
      function, we obtained monoclonal antibodies against the baculovirus-expressed
      protein. By immunoprecipitation and immunoblotting experiments, we showed that
      (i) NSP5 appears in many different phosphorylated forms in rotavirus-infected
      cells; (ii) immunoprecipitated NSP5 from rotavirus-infected cells can be
      phosphorylated in vitro by incubation with ATP; (iii) NSP5, produced either by
      transient transfection of rotavirus gene 11 or by infection by gene 11
      recombinant vaccinia virus or baculovirus, can be phosphorylated in vivo and in
      vitro; (iv) NSP5 expressed in Escherichia coli is phosphorylated in vitro, and
      thus NSP5 is a potential protein kinase; and (v) NSP5 forms dimers and interacts
      with NSP2. The intracellular localization of NSP5 in the course of rotavirus
      infection and after transient expression in COS7 cells has also been
      investigated. In rotavirus-infected cells, NSP5 is localized in viroplasms, but
      it is widespread throughout the cytoplasm of transfected COS7 cells. NSP5
      produced by transfected COS7 cells did not acquire the multiphosphorylated forms
      observed in rotavirus-infected COS7 cells. Thus, there is a tight correlation
      between the localization of NSP5 in the viroplasms and its protein kinase
      activity in vivo or in vitro. Our results suggest that cellular or viral
      cofactors are indispensable to fully phosphorylate NSP5 and to reach its
      intracellular localization.

PMID- 8985321
TI  - CD9, a tetraspan transmembrane protein, renders cells susceptible to canine
      distemper virus.
AB  - Canine distemper virus (CDV), a lymphotropic and neurotropic negative-stranded
      RNA virus of the Morbillivirus genus, causes a life-threatening disease in
      several carnivores, including domestic dogs. To identify the cellular receptor(s)
      involved in the uptake of CDV by susceptible cells, we isolated a monoclonal
      antibody (MAb K41) which binds to the cell surface and inhibits the CDV infection
      of several cell lines from various species. Pretreatment of cells with MAb K41
      reduces the number of infectious centers and the size of the syncytia. Using
      affinity chromatography with MAb K41, we purified from HeLa and Vero cell
      extracts a 26-kDa protein which contained the amino acid sequence TKDEPQRETLK of
      human CD9, a member of the tetraspan transmembrane or transmembrane 4 superfamily
      of cell surface proteins. Transfection of NIH 3T3 or MDBK cells with a CD9
      expression plasmid rendered these cells permissive for viral infection and raised
      virus production by a factor of 10 to 100. The mechanism involved is still
      unclear, since we were unable to detect direct binding of CDV to CD9 by using
      immunoprecipitation and a virus overlay protein binding assay. These findings
      indicate that human CD9 and its homologs in other species are necessary factors
      for the uptake of CDV by target cells, the formation of syncytia, and the
      production of progeny virus.

PMID- 8985322
TI  - Dose-dependent regulation of the early promoter of human papillomavirus type 18
      by the viral E2 protein.
AB  - The activity of the E6/E7 promoter of genital human papillomaviruses (HPVs) is
      positively and negatively modulated by a complex interplay between a variety of
      cellular transcription factors and the virally encoded E2 protein. The long
      control region of genital HPVs contains four E2 binding sites in conserved
      positions, two of which are very close to the TATA box. Binding of E2 to these
      two sites has been shown to repress the promoter. To carefully analyze the effect
      of E2 on the activity of the early promoter P105 of HPV18, we used an in vitro
      transcription system, which allowed titration of the amount of E2 protein. We
      found that low amounts of HPV18 E2 stimulated the promoter, whereas increasing
      amounts resulted in promoter repression. When the affinity was analyzed, it
      became obvious that E2 bound with highest affinity to E2 binding site 4 (BS-4),
      located 500 bp upstream of the promoter. The promoter most proximal binding site
      (BS-1) was the weakest site. Transient transfection assays confirmed that small
      amounts of HPV type (HPV18) E2 and also of bovine papillomavirus type 1 (BPV1) E2
      were able to activate the P105, which was dependent on an intact BS-4. The
      positive role of BS-4 was also obvious at higher E2 concentrations, since
      mutation of BS-4 enhanced repression. In contrast to HPV18 E2, BPV1 E2 bound
      better to BS-1 and, in correlation, was able to more strongly repress the P105 in
      vivo. Our results suggest a dose-dependent regulation of the HPV18 E6/E7 promoter
      by E2 due to variable occupancy of its binding sites, which have antagonizing
      effects on the activity of the E6/E7 promoter.

PMID- 8985323
TI  - Protein architecture of avian reovirus S1133 and identification of the cell
      attachment protein.
AB  - There are a number of discrepancies in the literature regarding the protein
      composition of the avian reoviruses. The present study demonstrates that avian
      reovirus S1133 contains at least 10 proteins (lambdaA, lambdaB, lambdaC, muA,
      muB, muBC, muBN, sigmaA, sigmaB, and sigmaC). Polypeptides muB, muBC, muBN,
      sigmaB, and sigmaC are components of the outer capsid layer of the virus, while
      lambdaA, lambdaB, muA, and sigmaA are core polypeptides. Protein lambdaC is a
      component of both layers, extending from the inner core to the outer capsid. The
      minor outer-capsid polypeptide sigmaC is shown to be the cell attachment protein,
      since it is the only viral polypeptide present in extracts of S1133-infected
      cells that binds specifically to chicken embryo fibroblasts; furthermore, its
      binding to avian cells was competitively inhibited by S1133 reovirions but not by
      mammalian reovirions. Our results also show that sigmaC is an oligomeric protein
      both in the virion and free in the cytoplasm, and preliminary results suggest
      that the multimer is made up of three monomeric units.

PMID- 8985324
TI  - Characterization of T-cell response to woodchuck hepatitis virus core protein and
      protection of woodchucks from infection by immunization with peptides containing
      a T-cell epitope.
AB  - Specific activation of T cells appears to be a prerequisite for viral clearance
      during hepatitis B virus (HBV) infection. The T-cell response to HBV core protein
      is essential in determining an acute or chronic outcome of HBV infection, but how
      this immune response contributes to the course of infection remains unclear. This
      is due to results obtained from humans, which are restricted to phenomenological
      observations occurring during the clinical onset after HBV infection. Thus, a
      useful animal model is needed. Characterization of the T-cell response to the
      core protein (WHcAg) of woodchuck hepatitis virus (WHV) in woodchucks contributes
      to the understanding of these mechanisms. Therefore, we investigated the response
      of woodchuck peripheral blood mononuclear cells (PBMCs) to WHcAg and WHcAg
      derived peptides, using our 5-bromo-2'-deoxyuridine assay. We demonstrated WHcAg
      specific proliferation of PBMCs and nylon wool-nonadherent cells from acutely WHV
      infected woodchucks. Using a cross-reacting anti-human T-cell (CD3) antiserum, we
      identified nonadherent cells as woodchuck T cells. T-cell epitope mapping with
      overlapping peptides, covering the entire WHcAg, revealed T-cell responses of
      acutely WHV-infected woodchucks to peptide1-20, peptide100-119, and peptide112
      131. Detailed epitope analysis in the WHcAg region from amino acids 97 to 140
      showed that T cells especially recognized peptide97-110. Establishment of
      polyclonal T-cell lines with WHcAg or peptide97-110 revealed reciprocal
      stimulation by peptide97-110 or WHcAg, respectively. We vaccinated woodchucks
      with peptide97-110 or WHcAg to prove the importance of this immunodominant T-cell
      epitope. All woodchucks immunized with peptide97-110 or WHcAg were protected. Our
      results show that the cellular immune response to WHcAg or to one T-cell epitope
      protects woodchucks from WHV infection.

PMID- 8985325
TI  - The human T-cell lymphotropic virus type 1 Tof protein contains a bipartite
      nuclear localization signal that is able to functionally replace the amino
      terminal domain of Rex.
AB  - The X region of human T-cell lymphotropic virus type 1 (HTLV-1) encodes two
      nucleolar/nuclear proteins, the posttranscriptional regulator of mRNA expression
      Rex and a protein of unknown function named Tof. To gain insight into the
      possible biological role of Tof, we investigated the mechanism governing its
      intracellular trafficking and identified its nucleolar/nuclear localization
      signal (NLS). Mutational analysis of Tof revealed that its NLS was located
      between amino acids 71 and 98 and contained two arginine-rich domains that
      functioned in an interdependent manner. Studies of Tof-Rex hybrid proteins showed
      that the Tof NLS could functionally replace the NLS of Rex at the level of
      nuclear targeting. As the NLS of Rex is known to mediate its interaction with its
      RNA target, the Rex-responsive element (RXRE), we tested whether the NLS of Tof
      could replace that of Rex in mediating activation of a RXRE-containing mRNA.
      Results showed that the NLS of Tof was indeed able to mediate activation of RXRE
      containing mRNAs, suggesting that Tof itself may function as a regulator of RNA
      expression and utilization. A comparison of their compartmentalization in
      response to actinomycin D treatment indicated that Tof did not share Rex's
      shuttling pathway. Expression of Tof from its natural multiply spliced mRNA
      required the presence of Rex, suggesting that Tof may regulate viral or cellular
      mRNA expression during the later stages of viral replication.

PMID- 8985326
TI  - Induction of an exceptionally high-level, nontranslated, Epstein-Barr virus
      encoded polyadenylated transcript in the Burkitt's lymphoma line Daudi.
AB  - An Epstein-Barr virus transcript (designated D-HIT [Daudi high-level-inducible
      transcript]), constitutively expressed at low levels in the Burkitt's lymphoma
      (BL)-derived cell line Daudi, can be induced with tetradecanoylphorbol acetate or
      n-butyrate or, in combination, to about 1% of the levels of high-molecular-weight
      RNAs in cells. The transcript can also be induced in some other EBV-positive BL
      derived cells but to a much lesser extent, particularly in lines that can give
      rise to productive infection. D-HIT is viral in origin and is composed largely of
      repetitive sequence. It is polyadenylated but mainly nuclear in location and is
      highly structured, sensitive only to double-strand-specific RNase. It is
      endogenously expressed in interferon-sensitive Daudi strains but not in an
      insensitive strain, Daudi 100K. D-HIT contains a part of a viral open reading
      frame (designated LF3, and deleted in the prototype B95-8 strain), using an
      internal polyadenylation (AAUAAA) sequence as a signal to specify processing of
      its 3' end. In Daudi cells, the promoter contains a putative hinge structure, as
      found in some interferon-inducible genes and c-myc. Since D-HIT lies adjacent to,
      probably even encompassing, one of the two viral lytic origins (D(R)) of
      replication, it may have a role in the regulation of DNA replication.
      Alternatively, or in addition via its double-stranded structure, D-HIT may play a
      regulatory role in interferon pathways. Its promoter could be of value for
      studying expression in constructions containing heterologous genes.

PMID- 8985327
TI  - Identification of an RNA sequence within an intracisternal-A particle element
      able to replace Rev-mediated posttranscriptional regulation of human
      immunodeficiency virus type 1.
AB  - Human immunodeficiency virus type 1 (HIV-1) replication depends on the
      posttranscriptional regulation by the viral Rev protein and can be replaced with
      the posttranscriptional RNA control element (CTE) of the type D simian
      retroviruses. We have identified a sequence which shares only nucleotide
      sequences of the internal loops and secondary structure with the CTE and which is
      part of a novel murine intracisternal-A particle (IAP) retroelement, inserted
      within the transcribed mouse osteocalcin-related gene. This sequence, named
      CTE(IAP), can replace the Rev-mediated regulation of HIV-1, hence it is a
      posttranscriptional regulatory element. Related elements have been identified in
      other IAPs. These results suggest that insertional mutagenesis can affect gene
      expression by providing a functional posttranscriptional control element. The
      CTE(IAP) and CTEs of the type D simian retroviruses represent a novel class of
      RNA elements characterized by unique sequences within the internal loops which
      are predicted to represent the interaction site with cellular factor(s). These
      findings suggest that such elements may be involved in posttranscriptional
      regulation of cellular mRNAs.

PMID- 8985328
TI  - The initiator element of the adenovirus major late promoter has an important role
      in transcription initiation in vivo.
AB  - Previous results showed that the structure and function of the adenovirus major
      late promoter (MLP) can be analyzed genetically in its correct location, despite
      its essential role in the viral life cycle. This genetic approach was extended to
      investigate the in vivo role of the initiator (INR), a transcriptional element
      that surrounds the start site of transcription. The analysis was designed to
      investigate if the INR is an alternative basal element to the canonical TATA box
      of the MLP, its relative importance in the functioning of the promoter, and if
      its function was affected by upstream activating elements. Accordingly, two
      different mutations in the INR were created and tested in the genome, either by
      themselves or together with mutations in the TATA box or one of the two upstream
      activating elements, the upstream promoter element (UPE) and the inverted CAAT
      box. The mutant viruses were examined first in one-step growth experiments, and
      then levels of late mRNA accumulation were measured by primer extension,
      transcription initiation was assayed in isolated nuclei, and viral DNA
      accumulation was determined by Southern hybridization. Neither mutation in the
      INR alone had any discernible phenotypic effects but when coupled to a
      phenotypically silent mutation in the TATA box gave rise to viruses with growth
      defects that were attributable to a significantly lowered rate of transcription
      initiation from the MLP. These results suggest that the INR plays a role in vivo
      and can act as an alternative basal element in the absence of a functioning TATA
      box. A virus with mutations in both the INR and the UPE, although viable,
      likewise had a severe deficiency in transcription, suggesting that the function
      of the INR is affected by that of the UPE. This contrasts with the previous
      report that a TATA box-UPE double mutation is not recoverable in virus. In
      addition, the virus with mutations in both the INR and the inverted CAAT box was
      phenotypically wild type, unlike the previously described TATA box-CAAT box
      double mutant, which had a severe transcription deficiency. Taken together, the
      present and previous genetic results can be interpreted as evidence that in the
      MLP, the TATA box and the UPE are the more important of the two basal and
      activating elements, respectively, but that the INR and CAAT can function in
      transcription initiation. We consider the role of the INR in the formation of the
      preinitiation complex and speculate on possible protein-protein interactions.

PMID- 8985329
TI  - Varicella-zoster virus Fc receptor gE glycoprotein: serine/threonine and tyrosine
      phosphorylation of monomeric and dimeric forms.
AB  - Varicella-zoster virus (VZV) glycoprotein gE is the predominant viral cell
      surface molecule; it behaves as an Fc receptor for immunoglobulin G, but its
      central function may be more closely related to viral egress and cell-to-cell
      spread. To further analyze the receptor properties of VZV gE, the gE gene (also
      called open reading frame 68) was expressed by a baculovirus vector in insect
      cells. The recombinant baculovirus gE product had a molecular mass of 64 kDa,
      smaller than the previously documented 98 kDa of mature gE expressed in mammalian
      cells. The major reason for the lowered molecular mass was diminished
      glycosylation. In addition to the 64-kDa form, a larger (130-kDa) form was
      observed in insect cells and represented dimerized 64-kDa molecules. Both the
      monomeric and dimeric gE forms were highly phosphorylated in insect cells.
      Protein kinase assays conducted in vitro with [gamma-32P]ATP and [gamma-32P]GTP
      indicated that endogenous casein kinase II was phosphorylating monomeric gE,
      while the dimeric gE form was phosphorylated by another kinase which did not
      utilize [gamma-32P]GTP. When immobilized recombinant gE molecules were probed
      with a monoclonal antibody which specifically recognizes a phosphotyrosine
      linkage, the gE dimer was found to be tyrosine phosphorylated whereas the monomer
      was not similarly modified. When recombinant gE produced in HeLa cells was probed
      with the same antiphosphotyrosine antibody, a dimeric gE form at 130 kDa was
      detected on the cell surface. These results suggested that VZV gE closely
      resembled other cell surface receptors, being modified on its various forms by
      both serine/threonine and tyrosine protein kinases. In this case, tyrosine
      phosphorylation occurred on a previously unrecognized and underglycosylated VZV
      gE dimeric product.

PMID- 8985330
TI  - Regulation of EBNA gene transcription in lymphoblastoid cell lines:
      characterization of sequences downstream of BCR2 (Cp).
AB  - During Epstein-Barr virus (EBV) latent infection of B lymphocytes in vitro, six
      EBV nuclear antigens (EBNAs) are expressed from one of two promoters, Cp and Wp,
      whose activities are mutually exclusive. Upon infection, Wp is initially active,
      followed by a switch to Cp for the duration of latency. In this study, the impact
      on Cp and Wp activity of sequences downstream of the distal EBNA gene promoter,
      Cp, was assessed in two lymphoblastoid cell lines. Cp activity was detected in
      constructs extending from just upstream of oriP to the first W1 exon. In
      contrast, Wp activity required the presence of the next downstream exon, W2.
      Viral sequences from -2199 to +2680 bp, relative to the Cp transcription start
      site, were dispensable for Wp activity. Sequences from +155 to +2680 bp, relative
      to the Cp transcription start site, were dispensable for Cp activity. Deletion of
      a 200-bp region from +2680 to +2880 bp downstream of Cp decreased both Cp and Wp
      activity two- to fivefold. Wp activity was also significantly diminished by
      deletion of the sequences from +2880 to +3000 bp downstream of the Cp
      transcription initiation site, which encompassed the Wp CCATT box. Based on
      deletion analyses of 10.3 kb of viral genomic sequence extending from just
      upstream of oriP to the first Wp, the only deletions which significantly
      upregulated Wp activity were those which abrogated Cp activity. However, reporter
      constructs in which the orientation of Cp was reversed displayed Wp activity
      comparable to that of reporter constructs in which Cp was deleted, even though
      the steady-state level of Cp-initiated transcripts from the inverted promoter was
      indistinguishable from that observed with Cp in normal orientation. This is the
      first direct evidence to support transcriptional interference as the mechanism
      for the mutually exclusive behavior of Cp and Wp.

PMID- 8985331
TI  - p300 family members associate with the carboxyl terminus of simian virus 40 large
      tumor antigen.
AB  - Several cellular polypeptides critical for growth regulation interact with DNA
      tumor virus oncoproteins. p400 is a cellular protein which binds to the
      adenovirus E1A oncoprotein(s). The biological function of p400 is not yet known,
      but it is structurally and immunologically closely related to p300 and CREB
      binding protein, two known E1A-binding transcription adapters. Like p300, p400 is
      a phosphoprotein that binds to the simian virus 40 large tumor antigen (T). In
      anti-T coimmunoprecipitation experiments, staggered deletions spanning the amino
      terminal 250 amino acids of T did not abrogate T binding to either p400 or p300.
      A T species composed of residues 251 to 708 bound both p400 and p300, while a T
      species defective in p53 binding was unable to bind either detectably. Anti-p53
      immunoprecipitates prepared from cells containing wild-type T also contained p400
      and p300. Hence, both p400 and p300 can bind (directly or indirectly) to a
      carboxyl-terminal fragment of T which contains its p53 binding domain. Since the
      p53 binding domain of T contributes to its immortalizing and transforming
      activities, T-p400 and/or T-p300 interactions may participate in these functions.

PMID- 8985333
TI  - The immunogenicity of intracerebral virus infection depends on anatomical site.
AB  - The brain parenchyma affords immune privilege to tissue grafts, but it is not
      known whether the same is true for intracerebral viral infections. Using
      stereotactically guided microinjection, we have confined infection with influenza
      virus A/NT/60/68 to either the brain parenchyma or the cerebrospinal fluid (CSF).
      A/NT/60/68 infection in the CSF elicited a comparable immune response to
      intranasal infection, with the production of antiviral serum antibody, priming of
      antiviral cytotoxic T-cell precursors, and an antiviral proliferative response in
      the draining lymph nodes. The response to virus in the CSF was detectable sooner
      after inoculation than the response to intranasal virus and also involved a
      prolonged production of virus-specific immunoglobulin A in the CSF. In contrast,
      there was no detectable immune response to virus infection in the brain
      parenchyma by any of the parameters measured for at least 10 days after
      inoculation. Over the next 80 days, 46% of the mice given parenchymal virus
      developed low-level immune responses that did not involve CSF antibody
      production, while the remaining 54% had no detectable response at any time. Thus,
      a virus infection confined to the parenchymal substance of the brain primed the
      immune system inefficiently or not at all.

PMID- 8985332
TI  - Serine protein kinase activity associated with rotavirus phosphoprotein NSP5.
AB  - The rotavirus nonstructural protein NSP5, a product of the smallest genomic RNA
      segment, is a phosphoprotein containing O-linked N-acetylglucosamine. We
      investigated the phosphorylation of NSP5 in monkey MA104 cells infected with
      simian rotavirus SA11. Immunoprecipitated NSP5 was analyzed with respect to
      phosphorylation and protein kinase activity. After metabolic labeling of NSP5
      with 32Pi, only serine residues were phosphorylated. Separation of tryptic
      peptides revealed four to six strongly labeled products and several weakly
      labeled products. Phosphorylation at multiple sites was also shown by two
      dimensional polyacrylamide gel electrophoresis (PAGE), where several isoforms of
      NSP5 with different pIs were identified. Analysis by PAGE of protein reacting
      with an NSP5-specific antiserum showed major forms at 26 to 28 and 35 kDa.
      Moreover, there were polypeptides migrating between 28 and 35 kDa. Treatment of
      the immunoprecipitated material with protein phosphatase 2A shifted the
      mobilities of the 28- to 35-kDa polypeptides to the 26-kDa position, suggesting
      that the slower electrophoretic mobility was caused by phosphorylation.
      Radioactive labeling showed that the 26-kDa form contained additional phosphate
      groups that were not removed by protein phosphatase 2A. The immunoprecipitated
      NSP5 possessed protein kinase activity. Incubation with [gamma-32P]ATP resulted
      in 32P labeling of 28- to 35-kDa NSP5. The distribution of 32P radioactivity
      between the components of the complex was similar to the phosphorylation in vivo.
      Assays of the protein kinase activity of a glutathione S-transferase-NSP5 fusion
      polypeptide expressed in Escherichia coli demonstrated autophosphorylation,
      suggesting that NSP5 was the active component in the material isolated from
      infected cells.

PMID- 8985334
TI  - Sequence identity of the terminal redundancies on the minus-strand DNA template
      is necessary but not sufficient for the template switch during hepadnavirus plus
      strand DNA synthesis.
AB  - The template for hepadnavirus plus-strand DNA synthesis is a terminally redundant
      minus-strand DNA. An intramolecular template switch during plus-strand DNA
      synthesis, which permits plus-strand DNA elongation, has been proposed to be
      facilitated by this terminal redundancy, which is 7 to 9 nucleotides long. The
      aim of this study was to determine whether the presence of identical copies of
      the redundancy on the minus-strand DNA template was necessary and/or sufficient
      for the template switch and at what position(s) within the redundancy the switch
      occurs for duck hepatitis B virus. When dinucleotide insertions were placed
      within the copy of the redundancy at the 3' end of the minus-strand DNA template,
      novel sequences were copied into plus-strand DNA. The generation of these novel
      sequences could be explained by complete copying of the redundancy at the 5' end
      of the minus-strand DNA template followed by a template switch and then extension
      from a mismatched 3' terminus. In a second set of experiments, it was found that
      when one copy of the redundancy had either three or five nucleotides replaced the
      template switch was inhibited. When the identical, albeit mutant, sequences were
      restored in both copies of the redundancy, template switching was not necessarily
      restored. Our results indicate that the terminal redundancy on the minus-strand
      DNA template is necessary but not sufficient for template switching.

PMID- 8985335
TI  - Clinical data sets of human immunodeficiency virus type 1 reverse transcriptase
      resistant mutants explained by a mathematical model.
AB  - Treatment of human immunodeficiency virus type 1 (HIV-1) infection during the
      clinical latency phase with drugs inhibiting reverse transcriptase (RT) reduces
      the HIV-1 RNA load and increases the CD4+ T-cell count. Typically, however, the
      virus evolves mutations in the RT gene that circumvent the drugs. We develop a
      mathematical model for this situation. The model distinguishes quiescent from
      activated CD4+ T cells, incorporates the fact that only activated cells can
      become productively infected by HIV-1, embodies empirical estimates for the drug
      resistance and the mutation frequency for each of the HIV-1 drug-resistant
      mutants, and assumes the antiviral immune response to remain constant over the
      course of the experiments. We analyze clinical data on the evolution of drug
      resistant mutants for the RT inhibitors lamivudine and zidovudine. The results
      show that the evolutionary sequence of the drug-resistant mutants in both data
      sets is accounted for by our model, given that lamivudine is more effective than
      zidovudine. Thus, current empirical estimates of the mutation frequencies and the
      drug resistances of the mutants suffice for explaining the data. We derive a
      critical treatment level below which the wild-type HIV-1 RNA load can rebound
      before the first drug-resistant mutant appears. Our zidovudine data confirm this
      to be the case. Thus, we demonstrate in the model and the data that the rebound
      of the HIV-1 RNA load in the case of zidovudine is due to the outgrowth of wild
      type virus and the first drug-resistant mutant, whereas that in the case of
      lamivudine can only be due to the drug-resistant mutants. The evolution of drug
      resistance proceeds slower in the case of zidovudine because (i) zidovudine is
      not as effective as lamivudine and (ii) the first zidovudine drug-resistant
      mutant is competing with the rebounding wild-type virus.

PMID- 8985336
TI  - Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis
      B surface antigen and interleukin-2.
AB  - DNA vaccines encoding a viral protein have been shown to induce antiviral immune
      responses and provide protection against subsequent viral challenge. In this
      study, we show that the efficacy of a DNA vaccine can be greatly improved by
      simultaneous expression of interleukin-2 (IL-2). Plasmid vectors encoding the
      major (S) or middle (pre-S2 plus S) envelope proteins of hepatitis B virus (HBV)
      were constructed and compared for their potential to induce hepatitis B surface
      antigen (HBsAg)-specific immune responses with a vector encoding the middle
      envelope and IL-2 fusion protein or with a bicistronic vector separately encoding
      the middle envelope protein and IL-2. Following transfection of cells in culture
      with these HBV plasmid vectors, we found that the encoded major protein was
      secreted while the middle protein and the fusion protein were retained on the
      cell membrane. Despite differences in localization of the encoded antigens,
      plasmids encoding the major or middle proteins gave similar antibody and T-cell
      proliferative responses in the vaccinated animals. The use of plasmids
      coexpressing IL-2 and the envelope protein in the fusion or nonfusion context
      resulted in enhanced humoral and cellular immune responses. In addition, the
      vaccine efficacy in terms of dosage used in immunization was increased at least
      100-fold by coexpression of IL-2. We also found that DNA vaccines coexpressing IL
      2 help overcome major histocompatibility complex-linked nonresponsiveness to
      HBsAg vaccination. The immune responses elicited by HBV DNA vaccines were also
      modulated by coexpression of IL-2. When restimulated with antigen in vitro,
      splenocytes from mice that received plasmids coexpressing IL-2 and the envelope
      protein produced much stronger T helper 1 (Th1)-like responses than did those
      from mice that had been given injections of plasmids encoding the envelope
      protein alone. Coexpression of IL-2 also increased the Th2-like responses,
      although the increment was much less significant.

PMID- 8985337
TI  - Human cytomegalovirus capsid assembly protein precursor (pUL80.5) interacts with
      itself and with the major capsid protein (pUL86) through two different domains.
AB  - We have used the yeast GAL4 two-hybrid system to examine interactions between the
      human cytomegalovirus (HCMV) major capsid protein (MCP, encoded by UL86) and the
      precursor assembly protein (pAP, encoded by UL80.5 and cleaved at its carboxyl
      end to yield AP) and found that (i) the pAP interacts with the MCP through
      residues located within the carboxy-terminal 21 amino acids of the pAP, called
      the carboxyl conserved domain (CCD); (ii) the pAP interacts with itself through a
      separate region, called the amino conserved domain (ACD), located between amino
      acids His34 and Arg52 near the amino end of the molecule; (iii) the simian CMV
      (SCMV) pAP and AP can interact with or replace their HCMV counterparts in these
      interactions, whereas the herpes simplex virus pAP and AP homologs cannot; and
      (iv) the HCMV and SCMV maturational proteinase precursors (ACpra, encoded by
      UL80a and APNG1, respectively) can interact with the pAP and MCP. The ACD and CCD
      amino acid sequences are highly conserved among members of the betaherpesvirus
      group and appear to have counterparts in the alpha- and gammaherpesvirus pAP
      homologs. Deleting the ACD from the HCMV pAP, or substituting Ala for a conserved
      Leu in the ACD, eliminated detectable pAP self-interaction and also substantially
      reduced MCP binding in the two-hybrid assay. This finding indicates that the pAP
      self-interaction influences the pAP-MCP interaction. Immunofluorescence studies
      corroborated the pAP-MCP interaction detected in the GAL4 two-hybrid experiments
      and showed that nuclear transport of the MCP was mediated by pAP but not AP. We
      conclude that the pAP interacts with the MCP, that this interaction is mediated
      by the CCD and is influenced by pAP self-interaction, and that one function of
      the pAP-MCP interaction may be to provide a controlled mechanism for transporting
      the MCP into the nucleus.

PMID- 8985338
TI  - Dextran sulfate can act as an artificial receptor to mediate a type-specific
      herpes simplex virus infection via glycoprotein B.
AB  - Herpes simplex virus (HSV) adsorption to host cells is mediated, at least in
      part, by the interaction of viral glycoproteins with cell surface
      glycosaminoglycans such as heparan sulfate and chondroitin sulfate. To
      investigate the contribution of various cell surface components in the infection
      pathway, we isolated a mutant cell line, sog9, which is unable to synthesize
      glycosaminoglycans (B. W. Banfield, Y. Leduc, L. Esford, K. Schubert, and F.
      Tufaro, J. Virol. 69:3290-3298, 1995). Although HSV-1 and HSV-2 infection of sog9
      cells is diminished, the cells are still infected at about 0.5% efficiency, which
      suggests that these cells normally express at least one nonglycosaminoglycan
      receptor. In this report, we used sog9 cells to test whether glycosaminoglycan
      analogs, such as dextran sulfate (DS), could functionally substitute for cellular
      glycosaminoglycans to initiate HSV infection. We show that high-molecular-weight
      DS added either prior to or during inoculation stimulated HSV-1 but not HSV-2
      infection by up to 35-fold; DS added after viral adsorption had no effect on
      infection efficiency. Moreover, DS stimulated HSV-1 infection at 4 degrees C,
      indicating that this compound impinged on an early, energy-independent step in
      infection. Using radiolabeled virus, we showed that HSV-1 is more efficient than
      HSV-2 in adsorbing to DS immobilized on microtiter wells. This raised the
      possibility that only HSV-1 could engage additional receptors to initiate
      infection in the presence of DS. To determine which viral component(s)
      facilitated DS stimulation, a panel of intertypic recombinants and deletion
      mutant viruses was investigated. These assays showed that DS stimulation of
      infection is mediated primarily by gB-1. Thus, this study provides direct
      evidence that a principal role for cell surface glycosaminoglycans in HSV
      infection is to provide an efficient matrix for virus adsorption. Moreover, by
      using DS as an alternative adsorption matrix (a trans receptor), we uncovered a
      functional, type-specific interaction of HSV-1 with a cell surface receptor.

PMID- 8985339
TI  - Functional interaction between the SH2 domain of Fyn and tyrosine 324 of hamster
      polyomavirus middle-T antigen.
AB  - Middle-T antigen of mouse polyomavirus (MomT) associates with the cellular
      tyrosine kinases c-Src, c-Yes, and Fyn, while middle-T antigen of hamster
      polyomavirus (HamT) exclusively binds Fyn. This interaction is essential for
      polyomavirus-mediated transformation of cells in culture and tumor formation in
      animals. Here we show that the kinase domain of Fyn is sufficient for association
      with MomT but not for binding of HamT. We further demonstrate that a Fyn mutant
      lacking the SH2 domain is able to bind MomT but fails to associate with HamT,
      indicating that the SH2 domain of Fyn is essential for stable association with
      HamT. HamT, but not MomT, contains a tyrosine residue, Tyr-324, in the sequence
      context YEEI. Mutation of Tyr-324 to phenylalanine led to a drastic reduction of
      associated Fyn and abolished the oncogenicity of HamT. This suggests that Tyr-324
      is the major phosphotyrosine residue mediating the binding of HamT to the SH2
      domain of Fyn. These findings show that mouse and hamster polyomaviruses use
      different strategies to target Src-related tyrosine kinases.

PMID- 8985340
TI  - Identification of a sequence within U5 required for human immunodeficiency virus
      type 1 to stably maintain a primer binding site complementary to tRNA(Met).
AB  - Initiation of reverse transcription of human immunodeficiency virus type 1 (HIV
      1) occurs by extension from the 3' end of a cellular tRNA complexed to the primer
      binding site (PBS) located near the 5' end of the viral RNA genome. Although the
      PBSs for all naturally occurring HIV-1 viruses are complementary to the 3'
      terminal 18 nucleotides of tRNA(Lys)3, we identified an HIV-1 virus which
      contained a PBS complementary to the 3' nucleotides of tRNA(Met); the PBS of this
      virus was not stable upon extended culture and reverted back to the wild type (S.
      M. Kang, J. K. Wakefield, and C. D. Morrow, Virology 222:401-414, 1996). To
      further characterize the virus with a PBS complementary to tRNA(Met), a DNA
      fragment encompassing the PBS and U5 region from this proviral genome was
      substituted for the same region in the infectious HIV-1 proviral clone [named
      pHXB2(AC-Met)]. Three additional proviral genomes were also created: pHXB2(Met),
      which is isogenic with pHXB2 except for the PBS complementary to tRNA(Met);
      pHXB2(Met-AC-Met), which contains the PBS sequence complementary to the 3'
      terminal nucleotides and the sequence upstream of this PBS in U5 complementary to
      the anticodon region of tRNA(Met); and pHXB2(Met-C-Met), which contains two G-to
      C changes predicted to disrupt complementarity within the tRNA(Met) anticodon
      region. Viruses derived from the transfection of these proviral genomes were
      infectious, although the appearance of the viruses was delayed compared to that
      of the wild-type virus. PCR amplification and DNA sequence analysis of the PBS
      regions from proviral genomes revealed that the PBSs from viruses derived from
      pHXB2(Met) and pHXB2(AC-Met) reverted back to the wild type by days 16 and 44
      postcoculture, respectively. Two new, novel mutant viruses were identified among
      viruses derived from pHXB2(Met-C-Met) at day 35 postcoculture: one contained a
      PBS complementary to tRNA(Lys)1,2, while the second maintained a PBS
      complementary to tRNA(Met) but contained a 26-nucleotide deletion in U5 upstream
      of the anticodon-complementary region. By day 125 postcoculture, the PBS in the
      virus from this culture had reverted back to the wild type, complementary to
      tRNA(Lys)3. In contrast, the viruses derived from pHXB2(Met-AC-Met) stably
      maintained a PBS complementary to tRNA(Met) during the 125-day culture period
      examined. The results of these studies support the idea that HIV-1 can maintain a
      PBS complementary to alternative tRNAs provided that the appropriate
      complementarity exists between the U5-PBS region of the viral RNA genome and the
      tRNA molecule used to initiate reverse transcription.

PMID- 8985341
TI  - Processing and membrane topology of the spike proteins G1 and G2 of Uukuniemi
      virus.
AB  - The membrane glycoproteins G1 and G2 of the members of the Bunyaviridae family
      are synthesized as a precursor from a single open reading frame. Here, we have
      analyzed the processing and membrane insertion of G1 and G2 of a member of the
      Phlebovirus genus, Uukuniemi virus. By expressing C-terminally truncated forms of
      the p10 precursor containing the whole of G1 and decreasing portions of G2, we
      found that processing in BHK21 cells occurred with an efficiency of about 50% if
      G1 was followed by 50 residues of G2, while complete processing occurred if 98,
      150, or 200 residues of G2 were present. Surprisingly, processing of all
      truncated G2 forms was less efficient in HeLa cells. Proteinase K treatment of
      microsomes isolated from infected cells indicated that the C terminus of G1 is
      exposed on the cytoplasmic face. Using G1 tail peptide antisera, the tail was
      likewise found by immunofluorescence to be exposed on the cytoplasmic face in
      streptolysin O-permeabilized cells. By introducing stop codons at various
      positions of the G1 tail and at the natural cleavage site between G1 and G2 and
      expressing these mutants in BHK cells, we found that no further processing of the
      G1 C terminus occurred following cleavage of G2 by the signal peptidase. This was
      also supported by the finding that an antiserum raised against a peptide
      corresponding to the region immediately upstream from the G2 signal sequence
      reacted in immunoblotting with G1 from virions. Finally, we show that both G1 and
      G2 are palmitylated. Taken together, these results show that processing of p10 of
      Uukuniemi virus occurs cotranslationally at only one site, i.e., downstream of
      the internal G2 signal sequence. G1 and G2 are inserted as type I proteins into
      the lipid bilayer, leaving the G1 tail exposed on the cytoplasmic face of the
      membrane. Since the G2 tail is only 5 residues long, the G1 tail is likely to be
      responsible for the interaction with the nucleoproteins during the budding
      process, in addition to harboring a Golgi localization signal.

PMID- 8985342
TI  - Inflammatory infiltration of the upper airway epithelium during Sendai virus
      infection: involvement of epithelial dendritic cells.
AB  - We undertook the present study to determine the nature of the cellular
      inflammatory response within the epithelial lining of the rat trachea during a
      Sendai virus infection. In particular, we aimed to investigate changes in the
      resident population of epithelial dendritic cells. Rats were infected with Sendai
      virus, and tracheal tissue was examined immunohistochemically at various times
      with a panel of cell-specific monoclonal antibodies. We found that Sendai virus
      infection was restricted to only the lumenal layer of epithelial cells and that
      virus nucleoprotein was present from days 2 to 5 postinfection. Starting around
      day 2 or 3, there was a large cellular influx consisting of macrophages,
      neutrophils, NK cells, and T cells; this coincided with expression of high levels
      of ICAM-1 on the basal (uninfected) layers of the epithelium. The T cells were
      mostly alphabeta T-cell receptor positive; however, a smaller influx of
      gammadelta T cells also took place. The number of resident dendritic cells
      increased markedly during infection, with numbers peaking around day 5 and
      remaining elevated 14 days later. The peak of the inflammatory response occurred
      on day 5 and declined thereafter, with the exception of dendritic cell and
      alphabeta T-cell numbers, which remained elevated. Starting around day 3, the
      tracheal epithelial cells expressed increasing levels of major histocompatibility
      complex class II antigen. This expression was maximal at day 5 and declined
      rapidly thereafter. In vitro culture of tracheal segments demonstrated that viral
      infection was not per se responsible for the upregulation of class II expression
      and that when cultured in the presence of gamma interferon, class II antigen was
      induced on epithelial cells.

PMID- 8985344
TI  - Packaging signals in alphaviruses.
AB  - Alphaviruses synthesize large amounts of both genomic and subgenomic RNA in
      infected cells, but usually only the genomic RNA is packaged. This implies the
      existence of an encapsidation or packaging signal which would be responsible for
      selectivity. Previously, we had identified a region of the Sindbis virus genome
      that interacts specifically with the viral capsid protein. This 132-nucleotide
      (nt) fragment lies within the coding region of the nsP1 gene (nt 945 to 1076). We
      proposed that the 132-mer is important for capsid recognition and initiates the
      formation of the viral nucleocapsid. To study the encapsidation of Sindbis virus
      RNAs in infected cells, we designed a new assay that uses the self-replicating
      Sindbis virus genomes (replicons) which lack the viral structural protein genes
      and contain heterologous sequences under the control of the subgenomic RNA
      promoter. These replicons can be packaged into viral particles by using defective
      helper RNAs that contain the structural protein genes (P. Bredenbeek, I. Frolov,
      C. M. Rice, and S. Schlesinger, J. Virol. 67:6439-6446, 1993). Insertion of the
      132-mer into the subgenomic RNA significantly increased the packaging of this RNA
      into viral particles. We have used this assay and defective helpers that contain
      the structural protein genes of Ross River virus (RRV) to investigate the
      location of the encapsidation signal in the RRV genome. Our results show that
      there are several fragments that could act as packaging signals. They are all
      located in a different region of the genome than the signal for the Sindbis virus
      genome. For RRV, the strongest packaging signal lies between nt 2761 and 3062 in
      the nsP2 gene. This is the same region that was proposed to contain the packaging
      signal for Semliki Forest virus genomic RNA.

PMID- 8985343
TI  - Cellular aging is a critical determinant of primary cell resistance to v-src
      transformation.
AB  - Primary cell cultures are in general resistant to the transforming effect of a
      single oncogene, a finding considered consistent with the multistage theory of
      carcinogenesis. In the present studies, we examined whether cellular age,
      differentiation stage, and/or tissue origin of primary cells plays a role in
      determining their response to v-src transformation. To study the role of cellular
      age, rat mammary fibroblasts were isolated from a 50-day-old female rat and
      infected with a recombinant retrovirus carrying a v-src gene after 2, 7, 14, 21,
      and 28 days of continuous growth. To determine whether cellular differentiation
      is important, fibroblasts were isolated from embryos at 12 and 16 days of
      gestation, from newborns, and from a 30-day-old rat and similarly infected.
      Finally, the role of primary-cell histogenesis was assessed by infecting primary
      cultures of fibroblasts isolated from the mammary gland, dermis, and lungs of a
      mature rat. When compared to 3Y1 cells, all preparations of primary cultures
      exhibited considerable resistance to v-src transformation. However, whereas
      primary cells isolated from different tissues responded similarly to the
      transforming effect of the oncogene, major differences were observed when cells
      were transduced at different stages of their in vitro life span. v-src was
      capable of inducing formation of foci and growth in soft agar in early-passage
      cells but failed to do so in primary cultures infected after 14 days of
      continuous passaging. Similarly, both the number of foci and the number of
      colonies in soft agar decreased with tissue donor age. The differential response
      of young and senescing cells could not be explained by mutations in v-src
      provirus, by differences in functional v-src expression, or by growth stimulation
      or suppression via paracrine mechanisms. Furthermore, v-src cooperated with an
      immortalizing gene, like simian virus 40 large T, polyomavirus large T, E6 and E7
      of human papillomavirus, or an activated p53 mutant, to induce anchorage
      independent growth of primary cultures but failed to do so with cytoplasmic
      transforming genes, like v-abl, v-ras, or v-raf, which did not confer indefinite
      division potential. These studies indicate that cellular aging is a critical
      determinant of primary-cell resistance to v-src transformation. It is suggested
      that v-src requires a nuclear auxiliary function for transformation which is
      present in early-passage cells, particularly when these cells are derived from
      embryonic tissue, but is lost as cells approach replicative senescence. This
      auxiliary function is provided by nuclear oncogenes but not cytoplasmic
      transforming genes.

PMID- 8985345
TI  - A novel human T-leukemia virus type 1 cell-to-cell transmission assay permits
      definition of SU glycoprotein amino acids important for infectivity.
AB  - Human T-leukemia virus type 1 (HTLV-1) envelope glycoproteins play a major role
      in viral transmission, which in the case of this virus occurs almost exclusively
      via cell-to-cell contact. Until very recently, the lack of an HTLV-1 infectivity
      assay precluded the determination of the HTLV-1 protein domains required for
      infectivity. Here, we describe an assay which allows the quantitative evaluation
      of HTLV-1 cell-to-cell transmission in a single round of infection. Using this
      assay, we demonstrate that in this system, cell-to-cell transmission is at least
      100 times more efficient than transmission with free viral particles. We have
      examined 46 surface (SU) glycoprotein mutants in order to define the amino acids
      of the HTLV-1 SU glycoprotein required for full infectivity. We demonstrate that
      these amino acids are distributed along the entire length of the SU glycoprotein,
      including the N-terminus and C-terminus regions, which have not been previously
      defined as being important for HTLV-1 glycoprotein function. For most of the
      mutated glycoproteins, the capacity to mediate cell-to-cell transmission is
      correlated with the ability to induce formation of syncytia. This result
      indicates that the fusion capacity is the main factor responsible for infectivity
      mediated by the HTLV-1 SU envelope glycoprotein, as is the case for other
      retroviral glycoproteins. However, other factors must also intervene, since two
      of the mutated glycoproteins were correctly fusogenic but could not mediate cell
      to-cell transmission. Existence of this phenotype shows that capacity for fusion
      is not sufficient to confer infectivity, even in cell-to-cell transmission, and
      could suggest that postfusion events involve the SU.

PMID- 8985346
TI  - Distinct organ-dependent mechanisms for the control of murine cytomegalovirus
      infection by natural killer cells.
AB  - Antiviral mechanisms by which natural killer (NK) cells control murine
      cytomegalovirus (MCMV) infection in the spleens and livers of C57BL/6 mice were
      measured, revealing different mechanisms of control in different organs. Three
      days postinfection, MCMV titers in the spleens of perforin 0/0 mice were higher
      than in those of perforin +/+ mice, but no elevation of liver titers was found in
      perforin 0/0 mice. NK cell depletion in MCMV-infected perforin 0/0 mice resulted
      only in an increase in liver viral titers and not in spleen titers. Depletion of
      gamma interferon (IFN-gamma) in C57BL/6 mice by injections with monoclonal
      antibodies to IFN-gamma resulted in an increase of viral titers in the liver but
      not in the spleen. Analyses using IFN-gamma-receptor-deficient mice, rendered
      chimeric with C57BL/6 bone marrow cells, indicated that in a recipient
      environment where IFN-gamma cannot exert its effects, the depletion of NK cells
      caused an increase in MCMV titers in the spleens but had little effect in the
      liver. IFN-gamma has the ability to induce a variety of cells to produce nitric
      oxide, and administrating the nitric oxide synthase inhibitor N(omega)-monomethyl
      L-arginine into MCMV-infected C57BL/6 mice resulted in MCMV titer increases in
      the liver but not in the spleen. Taken together, these data suggest that in
      C57BL/6 mice, there is a dichotomy in the mechanisms utilized by NK cells in the
      regulation of MCMV in different organs. In the spleen NK cells exert their
      effects in a perforin-dependent manner, suggesting a cytotoxic mechanism, while
      in the liver the production of IFN-gamma by NK cells may be a predominant
      mechanism in the regulation of MCMV synthesis. These results may explain why the
      Cmv-lr locus, which maps closely to genes regulating NK cell cytotoxic function,
      confers an NK cell-dependent resistance to MCMV infection in the spleen but not
      in the liver.

PMID- 8985347
TI  - Altered susceptibility to tumor necrosis factor alpha-induced apoptosis of mouse
      cells expressing polyomavirus middle and small T antigens.
AB  - Infection with some virus types induces susceptibility to the cytotoxic effect of
      tumor necrosis factor alpha (TNF-alpha). To investigate whether expression of
      polyomavirus proteins has this effect on cells, the TNF-alpha sensitivity of C127
      and L929 mouse cells transfected with viral DNA was analyzed. Expression of all
      three polyomavirus early proteins, the tumor (T) antigens, had no apparent
      effect. In contrast, middle T antigen by itself induced hypersensitivity to TNF
      alpha. This effect was reversed by retransfection of the cells with DNA encoding
      small T antigen. Expression of this polypeptide also decreased the sensitivity of
      bovine papillomavirus type 1-transformed cells to TNF-alpha, showing that the
      protective function of the polyomavirus small T antigen was not strictly linked
      to a middle-T-antigen-induced event. Mouse and human TNF-alpha had the same
      effect on normal and transformed mouse cells, suggesting that this effect was
      mediated by TNF receptor 1. Consistent with this conclusion, all cell clones used
      in the experiments expressed TNF receptor 1 at similar levels, while we failed to
      detect TNF receptor 2. The amount of receptor on the cells was not influenced by
      binding of the ligand. Addition of TNF-alpha at cytotoxic concentrations to cells
      expressing middle T antigen by itself resulted in significant fragmentation of
      chromosomal DNA after only a few hours, indicating induction of apoptosis.
      Addition of the cytokine to these cells also leads to release of arachidonic
      acid, showing that phospholipase A2 was activated. However, production of
      arachidonic acid did not appear to significantly precede loss of cell viability.

PMID- 8985348
TI  - Plasma viremia in macaques infected with simian immunodeficiency virus: plasma
      viral load early in infection predicts survival.
AB  - A reliable method for the quantitation of plasma viremia in nonhuman primates
      infected with simian immunodeficiency virus (SIV) and related viruses is
      described. This method is based on an established quantitative-competitive PCR
      format and includes a truncated control for internal assay calibration.
      Optimization of assay conditions has significantly improved amplification
      specificity, and interassay variability is comparable to that of commercially
      available assays for human immunodeficiency virus (HIV) quantitation. This
      procedure was used to monitor viral loads in a group of Macaca mulatta animals
      that were infected with SIVsmE660 for over 2 years. Highly diverse profiles of
      plasma viremia were observed among animals, and high viral loads were associated
      with more rapid disease progression. Spearman rank correlation analyses were done
      for survival versus three parameters of viral load: plasma viremia, p27 core
      antigen, and frequency of infected peripheral blood mononuclear cells. Plasma
      viremia had the strongest overall correlation and was significantly (P < 0.05 to
      P < 0.01) associated with survival at 10 of the 13 time points examined. Plasma
      viremia did not correlate with survival during the primary viremia phase;
      however, the strength of this correlation increased with time postinfection and,
      remarkably, viremia levels as early as week 6 postinfection were highly
      predictive (P < 0.01) of relative survival. These findings are consistent with
      the available clinical data concerning viral load correlates early in HIV
      infection, and they provide further support for the view that disease outcome in
      lentiviral infection may be largely determined by events that occur shortly after
      infection.

PMID- 8985349
TI  - Genetic analysis of the yellow fever virus NS1 protein: identification of a
      temperature-sensitive mutation which blocks RNA accumulation.
AB  - The flavivirus NS1 protein is a highly conserved nonstructural glycoprotein that
      is capable of eliciting protective immunity. NS1 homodimers are secreted from
      virus-infected mammalian cells, but the protein is also present at the plasma
      membrane and in the lumen of intracellular vesicles. Based on these properties,
      it has been speculated that NS1 may function in virus maturation or release. To
      gain further insight into NS1 function, we used clustered charged-amino-acid-to
      alanine mutagenesis to create 28 clustered substitutions in the NS1 protein of
      yellow fever virus. To screen for conditional mutations, full-length RNAs
      containing each mutation were assayed for plaque formation at 32 and 39 degrees C
      after RNA transfection. We found that 9 mutations were lethal, 18 allowed plaque
      formation at both temperatures, and 1, ts25, was strongly heat sensitive and was
      unable to form plaques at 39 degrees C. Lethal mutations clustered in the amino
      terminal half of NS1, whereas those leading to impaired replication relative to
      the parent were distributed throughout the protein. High-multiplicity infections
      at 39 degrees C demonstrated that ts25 was defective for RNA accumulation,
      leading to depressed viral protein synthesis and delayed virus production.
      Although ts25 secreted less NS1 than did the parent, temperature shift
      experiments failed to demonstrate any temperature-dependent differences in
      polyprotein processing, NS1 stability and secretion, or release of infectious
      virus. The ts lesion of ts25 was shown to be due to a single alanine substitution
      for Arg-299, a residue which is conserved among flaviviruses. These results argue
      that NS1 plays an essential but as yet undefined role in flavivirus RNA
      amplification.

PMID- 8985350
TI  - Efficiency of viral entry determines the capacity of murine erythroleukemia cells
      to support persistent infections by mammalian reoviruses.
AB  - To determine mechanisms by which persistent viral infections are established and
      maintained, we initiated persistent infections of murine erythroleukemia (MEL)
      cells by using reovirus strains type 3 Abney and type 3 Dearing. Establishment of
      persistent reovirus infections of MEL cells was not associated with a significant
      cytopathic effect despite the presence of high titers of infectious virus in the
      cultures (>10(5) PFU/ml of culture lysate). Maintenance of persistently infected
      MEL-cell cultures was associated with coevolution of mutant viruses and cells.
      Mutant viruses produced greater yields than the parental wild-type (wt) strains
      in MEL cells cured of persistent infection and in cells treated with ammonium
      chloride, a weak base that blocks viral disassembly. Mutant cells supported
      growth of wt infectious subvirion particles, which are disassembly intermediates
      generated in vitro by treatment of virions with chymotrypsin, substantially
      better than growth of wt virions. These findings indicate that viral and cellular
      mutations selected during maintenance of persistently infected MEL-cell cultures
      affect acid-dependent proteolysis of virions during entry into cells. We also
      found that wt infectious subvirion particles produce greater yields than wt
      virions in wt MEL cells, which suggests that inefficient viral disassembly in MEL
      cells favors establishment of persistent infection. Therefore, steps in reovirus
      replication leading to viral disassembly appear to be critical determinants of
      the capacity of MEL cells to support both establishment and maintenance of
      persistent reovirus infections.

PMID- 8985353
TI  - Three-dimensional structure of infectious bursal disease virus determined by
      electron cryomicroscopy.
AB  - Infectious bursal disease virus (IBDV), a member of the Birnaviridae group, is a
      commercially important pathogen of chickens. From electron micrographs of frozen,
      hydrated, unstained specimens, we have computed a three-dimensional map of IBDV
      at about 2 nm resolution. The map shows that the structure of the virus is based
      on a T=13 lattice and that the subunits are predominantly trimer clustered. The
      subunits close to the fivefold symmetry axes are at a larger radius than those
      close to the two- or threefold axes, giving the capsid a markedly nonspherical
      shape. The trimer units on the outer surface protrude from a continuous shell of
      density. On the inner surface, the trimers appear as Y-shaped units, but the set
      of units surrounding the fivefold axes appears to be missing. It is likely that
      the outer trimers correspond to the protein VP2, carrying the dominant
      neutralizing epitope, and the inner trimers correspond to protein VP3, which has
      a basic carboxy-terminal tail expected to interact with the packaged RNA.

PMID- 8985351
TI  - Genetic diversity of simian immunodeficiency viruses from West African green
      monkeys: evidence of multiple genotypes within populations from the same
      geographical locale.
AB  - High simian immunodeficiency virus (SIV) seroprevalence rates have been reported
      in the different African green monkey (AGM) subspecies. Genetic diversity of
      these viruses far exceeds the diversity observed in the other lentivirus-infected
      human and nonhuman primates and is thought to reflect ancient introduction of SIV
      in the AGM population. We investigate here genetic diversity of SIVagm in wild
      living AGM populations from the same geographical locale (i.e., sympatric
      population) in Senegal. For 11 new strains, we PCR amplified and sequenced two
      regions of the genome spanning the first tat exon and part of the transmembrane
      glycoprotein. Phylogenetic analysis of these sequences shows that viruses found
      in sympatric populations cluster into distinct lineages, with at least two
      distinct genotypes in each troop. These data strongly suggest an ancient
      introduction of these divergent viruses in the AGM population.

PMID- 8985352
TI  - Selective switch between latency and lytic replication of Kaposi's sarcoma
      herpesvirus and Epstein-Barr virus in dually infected body cavity lymphoma cells.
AB  - The BC-1 cell line, derived from a body cavity-based, B-cell lymphoma, is dually
      infected with Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated
      herpesvirus (KSHV). In these studies, the relationships between these two
      gammaherpesviruses and BC-1 cells were characterized and compared. Single-cell
      cloning experiments suggested that all BC-1 cells contain both genomes. In more
      than 98% of cells, both viruses were latent. The two viruses could be
      differentially induced into their lytic cycles by chemicals. EBV was activated
      into DNA replication and late-gene expression by the phorbol ester tetradecanoyl
      phorbol acetate (TPA). KSHV was induced into DNA replication and late-gene
      expression by n-butyrate. Amplification of both EBV and KSHV DNAs was inhibited
      by phosphonoacetic acid. Induction of the KSHV lytic cycle by n-butyrate was
      accompanied by the disappearance of host-cell beta-actin mRNA. Induction of EBV
      by TPA was not accompanied by such an effect on host-cell gene expression.
      Induction of the KSHV lytic cycle by n-butyrate was associated with the
      expression of several novel polypeptides. Recognition of one of these, p40,
      served as the basis of development of an assay for antibodies to KSHV in the sera
      of infected patients. BC-1 cells released infectious EBV; however, there was no
      evidence for the release of encapsidated KSHV genomes by BC-1 cells, even though
      n-butyrate-treated cells contained numerous intranuclear nucleocapsids. The
      differential inducibility of these two herpesviruses in the same cell line points
      to the importance of viral factors in the switch from latency to lytic cycle.

PMID- 8985354
TI  - Biochemical and functional analysis of the Borna disease virus G protein.
AB  - The Borna disease virus (BDV) antigenome is comprised of five major open reading
      frames (ORFs). Products have been reported only for ORFs I, II, and III, encoding
      N (p40), P (p24/p23), and M (gp18), respectively. ORF IV predicts a 57-kDa
      protein with several potential glycosylation sites. Analysis of radiolabeled
      extracts from BDV-infected C6 cells and BHK-21 cells transfected with a Semliki
      Forest virus vector that contains ORF IV demonstrated the presence of a 94-kDa
      protein (G protein) which was sensitive to tunicamycin, endoglycosidase F/N
      glycosidase, and endoglycosidase H but not to O-glycosidase. Sera from BDV
      infected rats detected the G protein and had neutralization activity that was
      reduced following immunoadsorption with the G protein. Preincubation of cells
      with the G protein interfered with BDV infectivity. This effect was enhanced by
      treatment of the G protein with the exoglycosidase alpha-mannosidase and reduced
      after subsequent treatment with N-acetyl-beta-D-glucosaminidase. In concert these
      findings indicate that ORF IV encodes a 94-kDa N-linked glycoprotein with
      extensive high mannose- and/or hybrid-type oligosaccharide modifications. The
      presence of neutralization epitopes on the G protein and its capacity to
      interfere with infectivity suggest that the G protein is important for viral
      entry.

PMID- 8985355
TI  - Function of the human T-cell leukemia virus type 1 21-base-pair repeats in basal
      transcription.
AB  - The human T-cell leukemia virus type 1 (HTLV-1) promoter contains three copies of
      an imperfect 21-bp repeat called Tax-responsive element (TRE1). To examine the
      role of individual TRE1 sequences in basal transcription of the HTLV-1 promoter,
      site-directed mutations were generated in all possible combinations of one, two,
      or all three TRE1 elements in the viral long terminal repeat (LTR) and tested in
      vivo for transcriptional activity. Mutation of the middle TRE1 resulted in the
      greatest reduction in basal activity. Electrophoretic mobility shift analysis
      demonstrated that the protein complexes bound to each of the three TRE1 sequences
      were not identical. The complexes formed with the TATA-distal and middle TRE1s
      were dependent on the core cyclic AMP response element (CRE) found in all three
      TRE1s, while the cellular transcription factor Sp1 bound the TATA-proximal TRE1
      in a CRE-independent manner. Sp1 binding produced a footprint on the viral LTR
      which covered the 5' region of the proximal TRE1. Mixing experiments demonstrated
      that the bindings of CREB and Sp1 to the proximal TRE1 were mutually exclusive.
      Sp1 was able to activate transcription both from the complete LTR and from the
      proximal TRE1 alone. These studies demonstrate that the TRE1 elements in the HTLV
      1 LTR are functionally nonequivalent and suggest that Sp1 can influence HTLV-1
      basal transcription.

PMID- 8985356
TI  - Posttranscriptional regulation of hepatitis B virus replication by the precore
      protein.
AB  - Hepadnaviruses encode two core-related open reading frames. One directs the
      synthesis of the p21 core protein, which subsequently becomes a structural
      component of the viral nucleocapsid. The other produces a p25 precore protein
      that is targeted by a signal peptide to a cell secretory pathway where N-terminal
      processing will create a p22 species. This molecule will be further modified at
      the C-terminal region to generate p17, and the truncated protein is secreted from
      the cell as hepatitis B e antigen (HBeAg). The function of the precore gene in
      the biology of hepadnaviruses is unknown. We found that ablation of the precore
      gene resulted in the generation of a hepatitis B virus (HBV) species with a high
      replication-level phenotype. More important, expression in trans of physiologic
      levels of p25 restored viral replication to wild-type levels. Moreover, transient
      or stable overexpression of the precore gene resulted in striking inhibition of
      HBV replication. The molecular species responsible for this viral inhibitory
      effect was identified as the p22 nonsecreted HBeAg precursor protein. By sucrose
      gradient sedimentation analysis, we determined that expression of p22 leads to
      the formation of nucleocapsids similar to those made with wild-type p21 core
      protein. Immunoprecipitation experiments revealed that the p21 and p22 physically
      interact and form hybrid nucleocapsid structures devoid of pregenomic viral RNA.
      These experiments suggest that expression of the precore gene may be important in
      the regulation of HBV replication and describe a possible molecular mechanism(s)
      for this effect.

PMID- 8985357
TI  - The Epstein-Barr virus EBNA-1 promoter Qp requires an initiator-like element.
AB  - Expression of the Epstein-Barr virus (EBV) EBNA-1 protein within EBV-positive
      tumor cells and subpopulations of latently infected B lymphocytes in vivo is
      mediated by the promoter Qp. Previous studies have established that Qp is a TATA
      less promoter whose activation requires only proximal regulatory elements and
      that it is negatively autoregulated through two EBNA-1 binding sites downstream
      of the transcription initiation sites. The objective of this study was to better
      define the properties of an essential positive regulatory element (QRE-2)
      adjacent to a major transcription start site of Qp and to evaluate the
      contributions of other potential regulatory elements proximal to the Qp start
      site. Using DNA affinity purification and UV cross-linking, we have identified
      the QRE-2-binding protein as a single polypeptide of approximately 40 kDa. The
      DNA-binding properties of this protein are clearly distinct from those of the
      TATA-binding protein, suggesting that in the absence of a TATA box, QRE-2 may
      function as an initiator element to direct assembly of TFIID near the
      transcription start site. Mutational analysis of potential regulatory elements,
      furthermore, indicated that the putative E2F binding sites within the EBNA-1
      binding domain can exert a positive influence on Qp that is EBNA-1 independent,
      suggesting that these regulatory elements play an additional if not different
      role in Qp regulation than previously proposed. A model for the regulation of Qp
      consistent with the current and previous findings which provides for a simple but
      efficient mechanism of ensuring the EBNA-1 expression necessary to sustain long
      term latency is presented.

PMID- 8985359
TI  - The vesicular stomatitis virus matrix protein inhibits transcription from the
      human beta interferon promoter.
AB  - In cells infected by wild-type (wt) vesicular stomatitis virus (VSV) Indiana,
      host transcription is severely inhibited. DNA cotransfection studies have
      implicated the VSV matrix (M) protein in this process (B. L. Black and D. S.
      Lyles, J. Virol. 66:4058-4064, 1992). The M protein inhibited transcription not
      only from viral promoters in plasmids but also from the chromosomally integrated
      human immunodeficiency virus type 1 (HIV-1) provirus promoter (S.-Y. Paik, A. C.
      Banerjea, G. G. Harmison, C.-J. Chen, and M. Schubert, J. Virol. 69:3529-3537,
      1995). In this study, we investigated the effect of wt VSV M protein on
      expression of a reporter gene under control of a cellular promoter (beta
      interferon [IFN-beta] promoter), using double transient transfections in BHK and
      COS-1 cells. The cellular IFN-beta promoter was as susceptible to the inhibitory
      effect of the M protein as the viral promoters used previously. Viral proteins N,
      P, and G had no significant effect on reporter gene expression. The M protein
      gene from VSV mutant T1026R1, which is defective in host transcription
      inhibition, was cloned and sequenced, and its effect on reporter gene expression
      was tested. The mutant M protein had a methionine-to-arginine change at position
      51 in the protein sequence and did not inhibit transcription from either the IFN
      beta promoter or viral promoters. This VSV mutant is a good inducer of IFN, as
      opposed to the wt virus, which suppresses IFN induction. These results show that
      the M protein inhibits transcription from cellular as well as viral promoters and
      that the M protein does not regulate the IFN promoter any differently from viral
      promoters. While the M protein may play a role in IFN gene regulation, other
      viral or cellular factors that provide specificity to the induction process must
      also be involved.

PMID- 8985358
TI  - Antioxidant-induced changes of the AP-1 transcription complex are paralleled by a
      selective suppression of human papillomavirus transcription.
AB  - Considering the involvement of a redox-regulatory pathway in the expression of
      human papillomaviruses (HPVs), HPV type 16 (HPV-16)-immortalized human
      keratinocytes were treated with the antioxidant pyrrolidine-dithiocarbamate
      (PDTC). PDTC induces elevated binding of the transcription factor AP-1 to its
      cognate recognition site within the viral regulatory region. Despite of increased
      AP-1 binding, normally indispensable for efficient HPV-16 transcription, viral
      gene expression was selectively suppressed at the level of initiation of
      transcription. Electrophoretic mobility supershift assays showed that the
      composition of the AP-1 complex, predominantly consisting of Jun homodimers in
      untreated cells, was altered. Irrespective of enhanced c-fos expression, c-jun
      was phosphorylated and became primarily heterodimerized with fra-1, which was
      also induced after PDTC incubation. Additionally, there was also an increased
      complex formation between c-jun and junB. Because both fra-1 and junB
      overexpression negatively interferes with c-jun/c-fos trans-activation of AP-1
      responsive genes, our results suggest that the observed block in viral
      transcription is mainly the consequence of an antioxidant-induced reconstitution
      of the AP-1 transcription complex. Since expression of the c-jun/c-fos gene
      family is tightly regulated during cellular differentiation, defined
      reorganization of a central viral transcription factor may represent a novel
      mechanism controlling the transcription of pathogenic HPVs during keratinocyte
      differentiation and in the progression to cervical cancer.

PMID- 8985360
TI  - Herpesvirus saimiri Tip-484 membrane protein markedly increases p56lck activity
      in T cells.
AB  - Herpesvirus saimiri (HVS) is a T-cell-specific transforming and oncogenic virus.
      A protein encoded by HVS known as Tip-484 (for tyrosine kinase interacting
      protein from HVS strain 484) is required for this transformation. Tip-484 binds
      specifically to the nonreceptor protein tyrosine kinase p56lck. By transfecting
      Tip-484 into T cells, we now show that this interaction leads to a several
      hundred-fold increase in the kinase activity of p56lck. Tip-484 is part of a
      protein complex which is dependent on the presence of p56lck and is
      phosphorylated. We also show that two of the complexed proteins represent two
      phosphorylated forms of Tip-484. Furthermore, the p56lck kinase activity in HVS
      infected human peripheral blood T lymphocytes was at least ninefold higher than
      that in noninfected control cells and significantly decreased in cells infected
      with a Tip-484 deletion mutant virus. Finally, we report that Tip-484 is required
      for oncogenesis in rabbits by the survival of rabbits inoculated with Tip-484
      deletion mutant HVS. The data demonstrate dramatic stimulation of the signaling
      pathway of p56lck. This effect can contribute to the molecular mechanisms that
      lead to sustained autocrine secretion of growth factors, permanent T-cell growth,
      and ultimately lymphocytic tumor formation.

PMID- 8985361
TI  - Mouse hepatitis virus is cleared from the central nervous systems of mice lacking
      perforin-mediated cytolysis.
AB  - Perforin-deficient [perforin (-/-)] mice were infected with two strains of JHM
      virus (JHMV) to analyze the role of perforin-mediated cytotoxicity in acute
      lethal and subacute central nervous system (CNS) infections. During both acute
      and subacute infections, the overall mortality of the perforin (-/-) mice was not
      different from that of the controls. Perforin (-/-) mice survived longer than the
      controls, consistent with reduced morbidity. Both strains of virus were cleared
      from the perforin (-/-) mice as in the controls; however, the rate of clearance
      was delayed in the perforin (-/-) mice, indicating that perforin-mediated
      cytolysis is involved in viral clearance. The absence of perforin-mediated
      cytolysis did not prevent encephalomyelitis or extensive demyelination. Cells
      undergoing apoptosis were detected in the CNS of both the perforin (-/-) and
      control groups, indicating that perforin is not essential for programmed cell
      death. Neutralizing antibodies were not detected in either group of mice until
      day 9 postinfection, when the majority of the virus had been cleared. These data
      further confirm the importance of cell-mediated cytotoxicity and suggest that
      additional components of the immune response contribute to the clearance of JHMV
      from the CNS.

PMID- 8985362
TI  - Critical residues of Semliki Forest virus RNA capping enzyme involved in
      methyltransferase and guanylyltransferase-like activities.
AB  - The Semliki Forest virus (SFV) replicase protein nsP1 has methyltransferase (MT)
      and guanylyltransferase-like (GT) activities, which are involved in the capping
      of viral mRNAs. MT catalyzes the transfer of the methyl group from S
      adenosylmethionine (AdoMet) to position 7 of GTP, and this reaction is followed
      by GT-catalyzed formation of the covalent complex m7GMP-nsP1. These reactions are
      virus specific and thus potential targets for inhibitors of virus replication. We
      have mutated residues of SFV nsP1, which are conserved in related proteins of the
      large alphavirus-like superfamily. Mutations of D64, D90, R93, C135, C142, and
      Y249 to alanine destroyed or greatly reduced the MT activity of nsP1. All MT
      negative mutants lost also the GT activity, confirming that methylation of GTP is
      an essential prerequisite for the synthesis of the covalent guanylate complex.
      Mutation of H38 prevented the GT reaction without destroying MT activity.
      Conservation of residues essential for both reactions in the alphavirus-like
      superfamily implies that they use a capping mechanism similar to that for the
      alphaviruses. Residues D64 and D90 were necessary for AdoMet binding, as measured
      by UV cross-linking. Secondary structure predictions of nsP1 and other proteins
      of the superfamily place these residues in positions corresponding to AdoMet
      binding sites of cellular methyltransferases, suggesting that they all may be
      structurally related.

PMID- 8985363
TI  - Adenovirus infection stimulates the Raf/MAPK signaling pathway and induces
      interleukin-8 expression.
AB  - Previous studies have shown that airway administration of adenovirus or
      adenovirus vectors results in a dose-dependent inflammatory response which limits
      the duration of transgene expression. We explored the possibility that adenovirus
      infection triggers signal transduction pathways that induce the synthesis of
      cytokines and thus contribute to the early inflammatory response. Since
      stimulation of the Raf/mitogen-activated protein kinase (MAPK) pathway activates
      transcription factors that control the expression of inflammatory cytokines, we
      examined the activation of this pathway following adenovirus infection.
      Adenovirus infection induced the rapid activation of Raf-1 and a transient
      increase in the tyrosine phosphorylation and activation of p42mapk at early times
      postinfection. Activation of the Raf/MAPK pathway by adenovirus is likely
      triggered by the infection process, since it occurred rapidly and with various
      mutant adenoviruses and adenovirus vectors. Moreover, interleukin-8 (IL-8) mRNA
      accumulation was evident at 20 min postinfection and was induced even in the
      presence of cycloheximide. Both MAPK activation and IL-8 production were
      inhibited by forskolin, a potent inhibitor of Raf-1. These results suggest that
      adenovirus-induced Raf/MAPK activation contributes to IL-8 production. Adenovirus
      induced activation of the Raf/MAPK signaling pathway and IL-8 production may play
      critical roles in the inflammation observed following in vivo administration of
      adenovirus vectors for gene therapy.

PMID- 8985364
TI  - The human cytomegalovirus UL97 protein is a protein kinase that
      autophosphorylates on serines and threonines.
AB  - The product of the human cytomegalovirus (CMV) UL97 gene, which controls
      ganciclovir phosphorylation in virus-infected cells, is homologous to known
      protein kinases but diverges from them at a number of positions that are
      functionally important. To investigate UL97, we raised an antibody against it and
      overexpressed it in baculovirus-infected insect cells. Recombinant baculovirus
      expressing full-length UL97 directed the phosphorylation of ganciclovir in insect
      cells, which was abolished by a four-codon deletion that confers ganciclovir
      resistance to CMV. When incubated with [gamma-32P]ATP, full-length UL97 was
      phosphorylated on serine and threonine residues. Phosphorylation was severely
      impaired by a point mutation that alters lysine-355 in a motif that aligns with
      subdomain II of protein kinases. However, phosphorylation was impaired much less
      severely by the four-codon deletion. A UL97 fusion protein expressed from
      recombinant baculovirus was purified to near homogeneity. It too was
      phosphorylated upon incubation with [gamma-32P]ATP in vitro. This
      phosphorylation, which was abolished by the lysine 355 mutation, was optimal at
      high NaCl and high pH. The activity required either Mn2+ or Mg2+, with a
      preference for Mn2+, and utilized either ATP or GTP as a phosphate donor, with
      Kms of 2 and 4 microM, respectively. The phosphorylation rate was first order
      with protein concentration, consistent with autophosphorylation. These data
      strongly argue that UL97 is a serine/threonine protein kinase that
      autophosphorylates and suggest that the four-codon deletion affects its substrate
      specificity.

PMID- 8985365
TI  - A single locus on human chromosome 21 directs the expression of a receptor for
      adenovirus type 2 in mouse A9 cells.
AB  - The receptors on human cells which mediate adsorption of adenoviruses have not
      been identified. We found that murine A9 cells and Chinese hamster ovary (CHO)
      cells failed to bind significant levels of radiolabeled adenovirus type 2 (Ad2)
      virions but that derivatives of these cells carrying human chromosome 21
      exhibited high levels of virus binding that was specific for the viral fiber
      protein. G418-resistant A9 cell transformants expressing Ad2 receptors were
      detected at a frequency of about 10(-4) following cotransfection with high
      molecular-weight DNAs from mouse cells containing human chromosome 21 and plasmid
      DNA containing a neomycin resistance gene. The Ad2 receptors on the transformed
      A9 cells were similar to those on human cells with respect to their concentration
      on the cell membrane, their affinity for the viral fiber protein, and their
      ability to direct virus into cells along a pathway leading to delivery of the
      viral DNA genome into the cell nucleus. Furthermore, identical human DNA
      fragments were present in three independent mouse cell transformants expressing
      Ad2 receptors, supporting the conclusion that these human DNA fragments
      correspond to a gene or locus on chromosome 21 that directs the expression of Ad2
      receptors in these cells.

PMID- 8985366
TI  - Identification of a T-helper cell epitope on the rotavirus VP6 protein.
AB  - In this work, we have studied the T-helper (Th)-cell response against rotavirus,
      in a mouse model. Adult BALB/c mice were inoculated parenterally with porcine
      rotavirus YM, and the Th-cell response from spleen cells against the virus and
      two overlapping fragments of the major capsid protein VP6 (VP6(1-192) and VP6(171
      397)) were evaluated in vitro. The Th cells recognized the YM virus and the two
      protein fragments, suggesting that there are at least two Th-cell epitopes on the
      VP6 molecule. To study the specificity of Th cells against VP6 at the clonal
      level, we established two Th-cell hybridomas cross-reactive for the VP6 protein
      of rotavirus strains YM and SA11. Both hybridomas recognized the VP6(171-397)
      polypeptide, and a synthetic peptide comprising the amino acids 289 to 302
      (RLSFQLVRPPNMTP) of YM VP6 in the context of the major histocompatibility complex
      class II IEd molecule. The Th-cell hybridomas recognized rotavirus VP6 in a
      highly cross-reactive fashion, since they could be stimulated by eight different
      strains of rotavirus, including the murine rotavirus EDIM, that represent five G
      serotypes and at least two subgroups. The amino acid sequence of the VP6 epitope
      is highly conserved in most group A rotavirus strains sequenced so far. On the
      other hand, it was found that Th cells specific for the VP6 epitope may
      constitute an important proportion of the total polyclonal Th-cell response
      against rotavirus YM in spleen cells. These results demonstrate that VP6 can be a
      target for highly cross-reactive Th cells.

PMID- 8985367
TI  - Direct modulation of simian virus 40 late gene expression by thyroid hormone and
      its receptor.
AB  - Transcription of the late genes of simian virus 40 (SV40) is repressed during the
      early phase of the lytic cycle of infection of primate cells by the binding of
      cellular factors, called IBP-s, to the SV40 late promoter; repression is relieved
      after the onset of viral DNA replication by titration of these repressors (S. R.
      Wiley, R. J. Kraus, F. R. Zuo, E. E. Murray, K. Loritz, and J. E. Mertz, Genes
      Dev. 7:2206-2219, 1993). Recently, we showed that IBP-s consists of several
      members of the steroid/thyroid hormone receptor superfamily (F. Zuo and J. E.
      Mertz, Proc. Natl. Acad. Sci. USA 92:8586-8590, 1995). Here, we show that the
      thyroid hormone receptor TRalpha1, in combination with retinoid X receptor alpha
      (RXRalpha), is specifically bound at the transcriptional initiation site of the
      major late promoter of SV40. This binding repressed transcription from the SV40
      late promoter by preventing the formation of pre-initiation complexes. Addition
      of the thyroid hormone 3,5,3'-L-triiodothyronine (T3) resulted in reversal of
      this repression in cotransfected CV-1 cells. Interestingly, repression did not
      occur when this thyroid response element (TRE) was translocated to 50 bp upstream
      of the major late initiation site. Binding of TRalpha1/RXRalpha heterodimers to
      this TRE induced bending of the promoter DNA. We conclude that hormones and their
      receptors can directly affect the expression of SV40, probably by affecting
      protein-protein and protein-DNA interactions involved in the formation of
      functional preinitiation complexes.

PMID- 8985368
TI  - Human endogenous retrovirus type I-related viruses have an apparently widespread
      distribution within vertebrates.
AB  - Retroviruses from lower vertebrate hosts have been poorly characterized to date.
      Few sequences have been isolated, and those which have been reported are all
      highly divergent when compared to the retroviruses known to be harbored by
      mammals and birds. Here we show that retroviruses with significant homology to
      the human endogenous retrovirus type I (HERV-I) are present within the genomes of
      fish, reptiles, birds, and mammals and that they may well be widespread within
      many vertebrates. Phylogenetic analysis of nucleotide sequences strongly
      supported the inclusion of viruses from each of these vertebrate classes into one
      monophyletic group. This analysis also demonstrated that the HERV-I-related
      viruses are more closely related to retroviruses belonging to the murine leukemia
      virus genus than to members of the other retroviral genera. The presence of HERV
      I-related retroviruses in so many disparate vertebrate hosts suggests that other
      endogenous human retroviruses may also have a much wider distribution than is
      currently appreciated.

PMID- 8985369
TI  - Analysis of cleavage site mutations between the NC and PR Gag domains of Rous
      sarcoma virus.
AB  - In retroviruses, the viral protease (PR) is released as a mature protein by
      cleavage of Gag, Gag-Pro, or Gag-Pro-Pol precursor polypeptides. In avian sarcoma
      and leukemia viruses (ASLV), PR forms the C-terminal domain of Gag. Based on the
      properties of a mutation (cs22) in the cleavage site between the upstream NC
      domain and the PR domain, the proteolytic liberation of PR previously was
      inferred to be essential for processing of Gag and Pol proteins. To study this
      process in more detail, we have analyzed the effects that several mutations at
      the NC-PR cleavage site have on proteolytic processing in virus-like particles
      expressed in COS and quail cells. Mutant Gag proteins carrying the same mutations
      also were synthesized in vitro and tested for processing with purified PR. In
      both types of studies, N-terminal sequencing of the liberated PR domain was
      carried out to exactly identify the site of cleavage. Finally, synthetic peptides
      corresponding to the mutant proteins were assessed for the ability to act as
      substrates for PR. The results were all consistent and led to the following
      conclusions. (i) In vivo, if normal processing between NC and PR is prevented by
      mutations, limited cleavage occurs at a previously unrecognized alternative site
      three amino acids downstream, i.e., in PR. This N-terminally truncated PR is
      inactive as an enzyme, as inferred from the global processing defect in cs22 and
      a similar mutant. (ii) In Gag proteins translated in vitro, purified PR cleaves
      this alternative site as rapidly as it does the wild-type site. (iii) Contrary to
      previously accepted rules describing retroviral cleavage sites, an isoleucine
      residue placed at the P1 position of the NC-PR cleavage site does not hinder
      normal processing. (iv) A proline residue placed at the P2 position in this
      cleavage site blocks normal processing.

PMID- 8985370
TI  - Internal entry of ribosomes is directed by the 5' noncoding region of classical
      swine fever virus and is dependent on the presence of an RNA pseudoknot upstream
      of the initiation codon.
AB  - Bicistronic RNAs containing the 373-nucleotide-long 5' nontranslated region (NTR)
      of the classical swine fever virus (CSFV) genome as intercistronic spacer were
      used to show the presence of an internal ribosome entry site (IRES) in the 5' end
      of the CSFV genome. By coexpression of the poliovirus 2A protease it was
      demonstrated that the CSFV 5' NTR-driven translation is independent of the
      presence of functional eukaryotic initiation factor eIF-4F. Deletion analysis
      indicated that the 5' border of the IRES is located between nucleotides 28 and
      66. The role of a proposed pseudoknot structure at the 3' end of the CSFV 5' NTR
      in IRES-mediated translation was investigated by site-directed mutagenesis.
      Mutant RNAs that had lost the ability to base pair in stem II of the pseudoknot
      were translationally inactive. Translation to wild-type levels could be restored
      through the introduction of compensatory complementary base changes that repaired
      base pairing in stem II. In addition, we showed that the AUG codon, which is
      located 7 nucleotides upstream of the polyprotein initiation site and is
      conserved in pestiviruses, could not be used to initiate translation. Also, an
      AUG codon introduced downstream of the polyprotein initiation site was not
      recognized as an initiation site by ribosomes. These data suggest that after
      internal entry on the CSFV 5' NTR, ribosomal scanning for the initiation codon is
      limited to a small region.

PMID- 8985371
TI  - Tethering human immunodeficiency virus type 1 preintegration complexes to target
      DNA promotes integration at nearby sites.
AB  - Integration of retroviral cDNA in vivo is normally not sequence specific with
      respect to the integration target DNA. We have been investigating methods for
      directing the integration of retroviral DNA to predetermined sites, with the dual
      goal of understanding potential mechanisms governing normal site selection and
      developing possible methods for gene therapy. To this end, we have fused
      retroviral integrase enzymes to sequence-specific DNA-binding domains and
      investigated target site selection by the resulting proteins. In a previous
      study, we purified and analyzed a fusion protein composed of human
      immunodeficiency virus integrase linked to the DNA-binding domain of lambda
      repressor. This fusion could direct selective integration in vitro into target
      DNA containing lambda repressor binding sites. Here we investigate the properties
      of a fusion integrase in the context of a human immunodeficiency virus provirus.
      We used a fusion of integrase to the DNA binding domain of the zinc finger
      protein zif268 (IN-zif). Initially we found that the fusion was highly
      detrimental to replication as measured by the multinuclear activation of a
      galactosidase indicator (MAGI) assay for infected centers. However, we found that
      viruses containing mixtures of wild-type integrase and IN-zif were infectious. We
      prepared preintegration complexes from cells infected with these viruses and
      found that such complexes directed increased integration near zif268 recognition
      sites.

PMID- 8985372
TI  - Productive and lytic infection of human CD4+ type 1 helper T cells with
      macrophage-tropic human immunodeficiency virus type 1.
AB  - It is generally recognized that macrophage-tropic human immunodeficiency virus
      type 1 (HIV-1) is the predominant population during the acute and asymptomatic
      phases of HIV-1 infection. Here, we compared the proliferation and syncytium
      inducing activities of different HIV-1 strains in primary CD4+ T cells expressing
      various helper T (Th)-type cytokine profiles. The macrophage-tropic HIV-1 strains
      HIV-1JR-CSF, HIV-1NFN-SX, and HIV-1SF162 could proliferate vigorously and
      generate syncytia in primary CD4+ T cells irrespective of their Th subtype, in
      contrast to the T-cell-line-tropic HIV-1 strains HIV-1NL4-3 and HIV-1IIIB, which
      favored non-type 1 Th conditions. These results indicate that macrophage-tropic
      HIV-1 may be more invasive and virulent, since it kills more CD4+ Th1 cells than
      T-cell-line-tropic HIV-1 during the early stages of HIV-1 infection, when the Th1
      immune response is dominant.

PMID- 8985374
TI  - Evidence for CD8+ T-cell immunity to murine rotavirus in the absence of perforin,
      fas, and gamma interferon.
AB  - We recently showed that class I-restricted CD8+ T cells mediate clearance of
      primary rotavirus infection in mice: JHD knockout (JHD -/-) (B-cell-deficient)
      mice depleted of CD8+ T cells become chronically infected with murine rotavirus,
      and beta2 microglobulin knockout (beta2m -/-) mice have delayed but complete
      clearance of primary rotavirus infection. In the present work we have analyzed
      the mechanism used by CD8+ T cells to clear rotavirus infection. We first
      determined that perforin knockout (perforin -/-) mice and lpr (fas-deficient)
      mice clear rotavirus infection with the same kinetics as control mice. When
      perforin -/- or perforin +/+ mice were depleted of CD8+ T cells by administration
      of an anti-CD8 monoclonal antibody, they showed a delay of 1 to 2 days in the
      clearance of rotavirus infection compared to the clearance time for untreated
      control mice, indicating that CD8+ T cells in both groups of mice participate in
      the resolution of primary rotavirus infection. In addition, passively transferred
      CD8+ T cells from rotavirus-infected perforin +/+ and perforin -/- mice were able
      to mediate viral clearance in Rag 2 knockout (Rag 2 -/-) mice chronically
      infected with rotavirus with similar kinetics, suggesting that CD8+ T cells from
      perforin -/- mice are as efficient as CD8+ T cells from perforin +/+ mice in
      clearing a rotavirus infection. Gamma interferon (IFN-gamma) was also shown to be
      unnecessary for the antirotavirus effect of CD8+ T cells: IFN-gamma knockout (IFN
      gamma -/-) mice and JHD -/-, perforin -/-, and perforin +/+ mice depleted of IFN
      gamma by administration of an anti-IFN-gamma monoclonal antibody cleared
      rotavirus infection with the same kinetics as those for control mice. Hence, CD8+
      T cells have an antirotaviral effect that is not mediated by perforin and appears
      to be independent of fas and the release of IFN-gamma.

PMID- 8985375
TI  - Approaches to determine stoichiometry of viral assembly components.
AB  - Due to the rapidity of biological reactions, it is difficult to isolate
      intermediates or to determine the stoichiometry of participants in intermediate
      reactions. Instead of determining the absolute amount of each component, this
      study involved the use of relative parameters, such as dilution factors,
      percentages probabilities, and slopes of titration curves, that can be more
      accurately quantified to determine the stoichiometry of components involved in
      bacteriophage phi29 assembly. This work takes advantage of the sensitive in vitro
      phage phi29 assembly system, in which 10(8) infectious virions per ml without
      background can be assembled from eight purified components. It provides a
      convenient assay for quantification of the stoichiometry of packaging components,
      including the viral procapsid, genomic DNA, DNA-packaging pRNA, and other
      structural proteins and enzymes. The presence of a procapsid binding domain and
      another essential functional domain within the pRNA makes it an ideal component
      for constructing lethal mutants for competitive procapsid binding. Two methods
      were used for stoichiometry determination. Method 1 was to determine the
      combination probability of mutant and wild-type pRNAs bound to procapsids. The
      probability of procapsids that possess a certain amount of mutant and a certain
      amount of wild-type pRNA, both with an equal binding affinity, was predicted with
      the binomial equation [EQUATION IN TEXT] where Z is the total number of pRNAs per
      procapsid, M is the number of mutant pRNAs bound to one procapsid, and (ZM) is
      equal to [FORMULA IN TEXT]. With various ratios of mutant to wild-type pRNA in in
      vitro viral assembly, the percent mutant pRNA versus the yield of virions was
      plotted and compared to a series of predicted curves to find a best fit. It was
      determined that five or six copies of pRNA were required for one DNA-packaging
      event, while only one mutant pRNA per procapsid was sufficient to block
      packaging. Method 2 involved the comparison of slopes of curves of dilution
      factors versus the yield of virions. Components with known stoichiometries served
      as standard controls. The larger the stoichiometry of the component, the more
      dramatic the influence of the dilution factor on the reaction. A slope of 1
      indicates that one copy of the component is involved in the assembly of one
      virion. A slope larger than 1 would indicate multiple-copy involvement. By this
      method, the stoichiometry of gp11 in phi29 particles was determined to be
      approximately 12. These approaches are useful for the determination of the
      stoichiometry of functional units involved in viral assembly, be they single
      molecules or oligomers. However, these approaches are not suitable for the
      determination of exact copy numbers of individual molecules involved if the
      functional unit is composed of multiple subunits prior to assembly.

PMID- 8985373
TI  - Authentic and chimeric full-length genomic cDNA clones of bovine viral diarrhea
      virus that yield infectious transcripts.
AB  - Bovine viral diarrhea virus (BVDV) is the most insidious and devastating viral
      pathogen of cattle in the United States. Disease control approaches must be based
      on detailed knowledge of virus biology. To develop reverse-genetic systems to
      study the molecular biology of the virus, we first constructed a plasmid
      containing the entire genome of BVDV cloned as cDNA. Subsequently, we showed that
      infectious BVDV was produced by cells transfected with uncapped RNA transcribed
      in vitro from the cDNA clone. This result defined functional 5' and 3' termini in
      viral genomic RNA and established the biological importance of the proposed
      internal ribosome entry site element in the 5' untranslated region of the viral
      genome. BVDV rescued from the infectious cDNA clone has an in vitro phenotype
      similar to that of the wild-type parent, the National Animal Disease Laboratory
      strain of BVDV. A deletion of a single codon in the full-length genomic BVDV cDNA
      clone, encoding glutamic acid at position 1600, gave rise to sequence-tagged
      virus easily identified by restriction fragment length polymorphism analysis of
      reverse transcription-PCR amplicons. Suitability of the molecular clone of BVDV
      for genomic manipulations was shown by substitution of the major envelope
      glycoprotein E2/gp53 with that of the Singer strain, giving rise to a chimeric
      virus. The predicted change in antigenic structure of the chimeric virus could be
      readily identified with strain-specific monoclonal antibodies by neutralization
      and immunofluorescence assays. Immediate applications of this system include
      development of safe and effective live vaccine strains possessing predetermined
      defined attenuating mutations.

PMID- 8985376
TI  - Magnesium-induced conformational change of packaging RNA for procapsid
      recognition and binding during phage phi29 DNA encapsidation.
AB  - Bacteriophage phi29 is typical of double-stranded DNA viruses in that its genome
      is packaged into a preformed procapsid during maturation. An intriguing feature
      of phi29 assembly is that a virus-encoded RNA (pRNA) is required for the
      packaging of its genomic DNA. Psoralen cross-linking, primer extension, and T1
      RNase partial digestion revealed that pRNA had at least two conformations; one
      was able to bind procapsids, and the other was not. In the presence of Mg2+, one
      stretch of pRNA, consisting of bases 31 to 35, was confirmed to be proximal to
      base 69, as revealed by its efficient cross-linking by psoralen. Two cross
      linking sites in the helical region were identified. Mg2+ induced a
      conformational change of pRNA that exposes the portal protein binding site by
      promoting the refolding of two strands of the procapsid binding region, resulting
      in the formation of pRNA-procapsid complexes. The procapsid binding region in
      this binding-competent conformation could not be cross-linked with psoralen. When
      the two strands of the procapsid binding region were fastened by cross-linking,
      pRNA could neither bind procapsids nor package phi29 DNA. A pRNA conformational
      change was also discernible by comparison of migration rates in native EDTA and
      Mg2+ polyacrylamide gel electrophoresis and was revealed by T1 RNase probing. The
      Mg2+ concentration required for the detection of a change in pRNA cross-linking
      patterns was 1 mM, which was the same as that required for pRNA-procapsid complex
      formation and DNA packaging and was also close to that in normal host cells.

PMID- 8985377
TI  - Replication of simian virus 40 origin-containing DNA during infection with a
      recombinant Autographa californica multiple nuclear polyhedrosis virus expressing
      large T antigen.
AB  - Autographica californica multiple nuclear polyhedrosis virus (AcMNPV) has been
      shown to encode many of the enzymes involved in the replication of its own DNA.
      Although the AcMNPV genome contains multiple sets of reiterated sequences that
      are thought to function as origins of DNA replication, no initiator protein has
      yet been identified in the set of viral replication enzymes. In this study, the
      ability of a heterologous origin initiator system to promote DNA replication in
      AcMNPV-infected cells was examined. A recombinant AcMNPV that expressed the
      simian virus 40 (SV40) large T antigen was surprisingly found to induce the
      efficient replication of a transfected plasmid containing an SV40 origin. This
      replication was subsequently found to involve three essential components: (i) T
      antigen, since replication of SV40 origin-containing plasmids was not induced by
      wild-type AcMNPV which did not express this protein; (ii) an intact SV40 core
      origin, since deletion of specific functional motifs within the origin resulted
      in a loss of replicative abilities; and (iii) one or more AcMNPV-encoded
      proteins, since viral superinfection was required for plasmid amplification.
      Characterization of the replicated DNA revealed that it existed as a high
      molecular-weight concatemer and underwent significant levels of homologous
      recombination between inverted repeat sequences. These properties were consistent
      with an AcMNPV-directed mode of DNA synthesis rather than that of SV40 and
      suggested that T antigen-SV40 origin complexes may be capable of initiating DNA
      replication reactions that can be completed by AcMNPV-encoded enzymes.

PMID- 8985378
TI  - Characterization of the ion channels formed by poliovirus in planar lipid
      membranes.
AB  - The steps in poliovirus infection leading to viral entry and uncoating are not
      well understood. Current evidence suggests that the virus first binds to a plasma
      membrane-bound receptor present in viable cells, leading to a conformational
      rearrangement of the viral proteins such that the virus crosses the membrane and
      releases the genomic RNA. The studies described in this report were undertaken to
      determine if poliovirus (160S) as well as one of the subviral particles (135S)
      could interact with membranes lacking poliovirus receptors in an effort to begin
      to understand the process of uncoating of the virus. We report that both forms of
      viral particles, 160S and 135S, interact with lipid membranes and induce the
      formation of ion-permeable channels in a manner that does not require acid pH.
      The channels induced by the viral particles 160S have a voltage-dependent
      conductance which depends on the ionic composition of the medium. Our findings
      raise the possibility that viral entry into cells may be mediated by direct
      interaction of viral surface proteins with membrane lipids.

PMID- 8985379
TI  - Phosphorylation of the hepatitis delta virus antigens.
AB  - We used two-dimensional electrophoresis (nonequilibrium pH gradient
      electrophoresis followed by sodium dodecyl sulfate-10% polyacrylamide gel
      electrophoresis) coupled with 32P labeling and immunoblotting detection with 125I
      protein A to detect and quantitate phosphorylation of the large and small forms
      of the delta antigen (deltaAg-L and deltaAg-S, respectively). Analysis of deltaAg
      species from the serum and liver of an infected woodchuck as well as deltaAg
      species expressed in and secreted from transfected Huh7 cells revealed the
      following. (i) No detectable phosphorylation of deltaAg-S occurred. (ii) In
      virions from the serum of an infected animal and in the particles secreted from
      cotransfected cells, none of the deltaAg-L was phosphorylated. (iii) Only in the
      infected liver and in transfected cells was any phosphorylation detected; it
      corresponded to a monophosphorylated form of deltaAg-L. Given these results, we
      carried out serine-to-alanine mutagenesis of the deltaAg-L to determine whether
      the monophosphorylation was predominantly at a specific site on the unique 19
      amino-acid (aa) extension. We mutated each of the two serines, aa 207 and 210, on
      this extension and also the serine at aa 177. These three mutations had no
      significant effect on phosphorylation. In contrast, mutagenesis to alanine of the
      cysteine at aa 211, which normally acts as the acceptor for farnesylation,
      completely inhibited phosphorylation. Our interpretation is that the site(s) of
      phosphorylation is probably not in the 19-aa extension unique to deltaAg-L and
      that phosphorylation of deltaAg-L may depend upon prior farnesylation. The
      possible significance of the intracellular phosphorylated forms of deltaAg-L is
      discussed.

PMID- 8985380
TI  - Epithelial cell polarization is a determinant in the infectious outcome of
      immunoglobulin A-mediated entry by Epstein-Barr virus.
AB  - Diseases of the nasopharyngeal epithelium due to Epstein-Barr virus (EBV)
      infection typically occur in chronic virus carriers with preexisting virus
      specific antibodies. In vitro studies have shown that EBV-specific immunoglobulin
      A (IgA) promotes infection of human epithelial cells, otherwise refractory to
      EBV, via the polymeric immunoglobulin receptor (pIgR). To determine if EBV
      similarly exploits IgA transport mechanisms in vivo, we examined the fate of IgA
      EBV complexes in the blood of mice, where pIgR-mediated transcytosis of IgA
      immune complexes through hepatocytes eliminates exogenous antigens from the
      circulation. By PCR analysis we showed hepatobiliary transport of IgA-EBV in
      viremic mice, but without detectable hepatocellular infection by immunostaining.
      Because efficient transport of EBV immune complexes might avert an infectious
      outcome, we modulated the transcytotic pathway in polarized Madin-Darby canine
      kidney (MDCK) cells transfected with pIgR to determine the effect on viral
      antigen expression. Like hepatocytes in vivo, MDCK cells in polarized monolayers
      translocated IgA-EBV from the basal cell face into apical medium without evidence
      for infection. However, when exposed to IgA-EBV as unpolarized single-cell
      suspensions, MDCK cells expressed EBV immediate-early and early antigens. These
      results suggest that pIgR-mediated transcytosis of pIgA-EBV through epithelium
      facilitates endogenous spread of EBV in long-term virus carriers, with infection
      being confined to cells with altered polarity from prior cytopathology.

PMID- 8985381
TI  - Characterization of an abundant, unique 1.7-kilobase bovine herpesvirus 4 (BHV-4)
      late RNA and mapping of a BHV-4 IE2 transactivator-binding site in its promoter
      regulatory region.
AB  - We characterized an abundant late 1.7-kb cytoplasmic polyadenylated RNA (L1.7
      RNA) transcribed from the bovine herpesvirus 4 (BHV-4) HindIII W fragment, in a
      region of the genome not conserved with Epstein-Barr virus and herpesvirus
      saimiri. L1.7 RNA contains only extremely short (<100 nucleotides) open reading
      frames followed by two repeat arrays. The first repeat array contains 11 copies
      of a 23-bp unit, TGGCACTA GTAGCATTTAACCCC. The second and third copies are each
      interrupted by 15- to 17-bp sequences that are identical to each other for the
      first 15 bp. In addition, the second and third copies of the repeat unit each
      contain two copies of nucleotides 5 to 9 (ACTAG) of the repeat unit, one at each
      end of the interruption. The second repeat array contains 12 copies of a 25-bp
      sequence, GCTGTGTATTATTGAGTATTTTTTA. The promoter-regulatory region of L1.7 was
      activated by the BHV-4 immediate-early gene 2 product (IE2), a homolog of the
      Epstein-Barr virus R transactivator, in cotransfection assays. We mapped an IE2
      recognition site within a 167-bp fragment approximately 10 bp 5' to the start of
      L1.7 RNA transcription, using cotransfection assays and gel retardation assays.
      Using gel retardation assays, we mapped an IE2-binding site within this fragment
      to a 31-bp region from 56 to 86 bp 5' to the start of L1.7 RNA transcription.
      This IE2-binding site was able to transfer IE2 responsiveness to a heterologous
      promoter. However, IE2 responsiveness was affected by both position and
      orientation. Alignment of the L1.7 IE2-binding site sequence with sequences of
      two other BHV-4 IE2-binding sites resulted in a provisional IE2-binding site
      consensus sequence different from the Epstein-Barr virus R transactivator-binding
      site.

PMID- 8985382
TI  - Domain organization of the adenovirus preterminal protein.
AB  - In adenovirus-infected cells, the virus-encoded preterminal protein and DNA
      polymerase form a heterodimer that is directly involved in initiation of DNA
      replication. Monoclonal antibodies were raised against preterminal protein, and
      epitopes recognized by the antibodies were identified by using synthetic
      peptides. Partial proteolysis of preterminal protein reveals that it has a
      tripartite structure, with the three domains being separated by two protease
      sensitive areas, located at sites processed by adenovirus protease. These areas
      of protease sensitivity are probably surface-exposed loops, as they are the
      sites, along with the C-terminal region of preterminal protein, recognized by the
      monoclonal antibodies. Preterminal protein is protected from proteolytic cleavage
      when bound to adenovirus DNA polymerase, suggesting either multiple contact
      points between the proteins or a DNA polymerase-induced conformational change in
      preterminal protein. Two of the preterminal protein-specific antibodies induced
      dissociation of the preterminal protein-adenovirus DNA polymerase heterodimer and
      inhibited initiation of adenovirus DNA replication in vitro. Antibodies binding
      close to the primary processing sites of adenovirus protease inhibited DNA
      binding, consistent with UV cross-linking results which reveal that an N
      terminal, protease-resistant domain of preterminal protein contacts DNA.
      Monoclonal antibodies recognizing epitopes within the C-terminal 60 amino acids
      of preterminal protein stimulate DNA binding, an effect mediated through a
      decrease in the dissociation rate constant. These results suggest that
      preterminal protein contains a large, noncontiguous surface required for
      interaction with DNA polymerase, an N-terminal DNA binding domain, and a C
      terminal regulatory domain.

PMID- 8985383
TI  - The early region 1B 55-kilodalton oncoprotein of adenovirus relieves growth
      restrictions imposed on viral replication by the cell cycle.
AB  - The E1B 55-kDa oncoprotein of adenovirus enables the virus to overcome
      restrictions imposed on viral replication by the cell cycle. Approximately 20% of
      HeLa cells infected with an E1B 55-kDa mutant adenovirus produced virus when
      evaluated by electron microscopy or by assays for infectious centers. By
      contrast, all HeLa cells infected with a wild-type adenovirus produced virus. The
      yield of E1B mutant virus from randomly cycling HeLa cells correlated with the
      fraction of cells in S phase at the time of infection. In synchronously growing
      HeLa cells, approximately 75% of the cells infected during S phase with the E1B
      mutant virus produced virus, whereas only 10% of the cells infected during G1
      produced virus. The yield of E1B mutant virus from HeLa cells infected during S
      phase was sevenfold greater than that of cells infected during G1 and threefold
      greater than that of cells infected during asynchronous growth. Cells infected
      during S phase with the E1B mutant virus exhibited severe cytopathic effects,
      whereas cells infected with the E1B mutant virus during G1 exhibited a mild
      cytopathic effect. Viral DNA synthesis appeared independent of the cell cycle
      because equivalent amounts of viral DNA were synthesized in cells infected with
      either wild-type or E1B mutant virus. The inability of the E1B mutant virus to
      replicate was not mediated by the status of p53. These results define a novel
      property of the large tumor antigen of adenovirus in relieving growth
      restrictions imposed on viral replication by the cell cycle.

PMID- 8985384
TI  - Improvement of the specific infectivity of the rubella virus (RUB) infectious
      clone: determinants of cytopathogenicity induced by RUB map to the nonstructural
      proteins.
AB  - A plasmid, Robo102, which contains a cDNA copy of the rubella virus (RUB) genomic
      RNA from which infectious transcripts can be synthesized in vitro, was recently
      developed (C. Y. Wang, G. Dominguez, and T. K. Frey, J. Virol. 68:3550-3557,
      1994). To increase the specific infectivity of Robo102 transcripts (approximately
      5 plaques/10 microg of transcripts), a modified reverse transcription-PCR method
      was used to amplify nearly 90% of the RUB genome in three fragments, which were
      then used to replace the corresponding fragments in Robo102. Replacement of a
      fragment covering nucleotides (nt) 5352 to 9759 of the RUB genome yielded a
      construct, Robo202, which produced highly infectious transcripts (10(4)
      plaques/microg), indicating the presence of an unrecognized deleterious mutation
      (or mutations) in this region of the Robo102 cDNA. Robo102 was based on the w
      Therien strain of RUB, which forms opaque plaques in Vero cells, while the PCR
      replacement fragments were generated from a variant, f-Therien, which produces
      clear plaques in Vero cells. Although Robo202 contains over 4,000 nt from f
      Therien, Robo202 virus produces opaque plaques. However, when the other two PCR
      fragments amplified from f-Therien (nt 1 to 1723 and nt 2800 to 5352) were
      introduced into Robo202, the resulting construct, Robo302, yielded transcripts
      that produced a virus that formed clear plaques. This indicates that the
      determinants of plaque morphology map to the regions of the genome covered by
      these two fragments, both of which are in the nonstructural open reading frame.
      Generation of Robo202/302 chimeras indicated that the most 5' terminal fragment
      (nt. 1 to 1723) had the greatest effect on plaque morphology. The plaque
      morphology was correlated with the ability of the viruses to kill infected cells.
      The only difference at the molecular level detected among the viruses was that
      the more cytopathic viruses produced more nonstructural proteins than did the
      less cytopathic viruses. This finding, as well as the mapping of the genetic
      determinants to the region of the genome encoding these proteins, indicates that
      the nonstructural proteins can mediate cell killing.

PMID- 8985385
TI  - In vitro interactions of the aphid endosymbiotic SymL chaperonin with barley
      yellow dwarf virus.
AB  - Barley yellow dwarf virus (BYDV)-vector relationships suggest that there are
      specific interactions between BYDV virions and the aphid's cellular components.
      However, little is known about vector factors that mediate virion recognition,
      cellular trafficking, and accumulation within the aphid. Symbionins are molecular
      chaperonins produced by intracellular endosymbiotic bacteria and are the most
      abundant proteins found in aphids. To elucidate the potential role of symbionins
      in BYDV transmission, we have isolated and characterized two new symbionin symL
      genes encoded by the endosymbionts which are harbored by the BYDV aphid vectors
      Rhopalosiphum padi and Sitobion avenae. Endosymbiont symL-encoded proteins have
      extensive homology with the pea aphid SymL and Escherichia coli GroEL chaperonin.
      Recombinant and native SymL proteins can be assembled into oligomeric complexes
      which are similar to the GroEL oligomer. R. padi SymL protein demonstrates an in
      vitro binding affinity for BYDV and its recombinant readthrough polypeptide. In
      contrast to the R. padi SymL, the closely related GroEL does not exhibit a
      significant binding affinity either for BYDV or for its recombinant readthrough
      polypeptide. Comparative sequence analysis between SymL and GroEL was used to
      identify potential SymL-BYDV binding sites. Affinity binding of SymL to BYDV in
      vitro suggests a potential involvement of endosymbiotic chaperonins in
      interactions with virions during their trafficking through the aphid.

PMID- 8985386
TI  - Processing of a cellular polypeptide by 3CD proteinase is required for poliovirus
      ribonucleoprotein complex formation.
AB  - Poliovirus interactions with host cells were investigated by studying the
      formation of ribonucleoprotein complexes at the 3' end of poliovirus negative
      strand RNA which are presumed to be involved in viral RNA synthesis. It was
      previously shown that two host cell proteins with molecular masses of 36 and 38
      kDa bind to the 3' end of viral negative-strand RNA at approximately 3 to 4 h
      after infection. We tested the hypothesis that preexisting cellular proteins are
      modified during the course of infection and are subsequently recruited to play a
      role in viral replication. It was demonstrated that the 38-kDa protein, either
      directly or indirectly, is the product of processing by poliovirus 3CD/3C
      proteinase. Only the modified 38-kDa protein, not its precursor protein, has a
      high affinity for binding to the 3' end of viral negative-strand RNA. This
      modification depends on proteolytically active proteinase, and a direct
      correlation between the levels of 3CD proteinase and the 38-kDa protein was
      demonstrated in infected tissue culture cells. The nucleotide (nt) 5-10 region
      (positive-strand numbers) of poliovirus negative-strand RNA is important for
      binding of the 38-kDa protein. Deletion of the nt 5-10 region in full-length,
      positive-strand RNA renders the RNA noninfectious in transfection experiments.
      These results suggest that poliovirus 3CD/3C proteinase processes a cellular
      protein which then plays an essential role during the viral life cycle.

PMID- 8985387
TI  - Epstein-Barr virus LMP1 induction of the epidermal growth factor receptor is
      mediated through a TRAF signaling pathway distinct from NF-kappaB activation.
AB  - The Epstein-Barr virus (EBV)-encoded LMP1 protein induces several cellular
      changes including induction of epidermal growth factor receptor (EGFR) expression
      and activation of the NF-kappaB transcription factor. Two domains within the
      carboxy terminus have been identified that activate NF-kappaB. In this study,
      mutational analysis of the LMP1 protein indicated that the proximal NF-kappaB
      activation domain, which is identical to the TRAF interaction domain (amino acids
      187 to 231), is essential for induction of the EGFR. The distal NF-kappaB
      activation domain (amino acids 352 to 386) did not induce expression of the EGFR.
      In contrast, the two domains both independently activated a kappaB-CAT reporter
      gene and induced expression of the NF-kappaB-regulated A20 gene in C33A
      epithelial cells. These results indicate that induction of the EGFR by LMP1
      involves the TRAF interaction domain and that activation of NF-kappaB alone is
      not sufficient. Northern blot analysis revealed that induction of EGFR and A20
      expression is likely to be at the transcriptional level. Interestingly expression
      of CD40 in the C33A cells also induced expression of the EGFR. Overexpression of
      either TRAF3 or an amino-terminal-truncated form of TRAF3 (TRAF3-C) inhibited
      signaling from the LMP1 TRAF interaction domain but did not affect signaling from
      the distal NF-kappaB activation domain. These data further define the mechanism
      by which LMP1 induces expression of the EGFR and indicate that TRAF signaling
      from LMP1 and CD40 activates a downstream transcription pathway distinct from NF
      kappaB that induces expression of the EGFR.

PMID- 8985388
TI  - Tyrosine phosphorylation events during coxsackievirus B3 replication.
AB  - In order to study cellular and viral determinants of pathogenicity, interactions
      between coxsackievirus B3 (CVB3) replication and cellular protein tyrosine
      phosphorylation were investigated. During CVB3 infection of HeLa cells, distinct
      proteins become phosphorylated on tyrosine residues, as detected by the use of
      antiphosphotyrosine Western blotting. Two proteins of 48 and 200 kDa showed
      enhanced tyrosine phosphorylation 4 to 5 h postinfection (p.i.), although virus
      induced inhibition of cellular protein synthesis had already occurred 3 to 4 h
      p.i. Subcellular fractionation experiments revealed distinct localization of
      tyrosine-phosphorylated proteins of 48 and 200 kDa in the cytosol and membrane
      fractions of infected cells, respectively. In addition, in Vero cells infected
      with CVB3, echovirus (EV)11, or EV12, increased tyrosine phosphorylation of a 200
      kDa protein was detected 6 h p.i. Herbimycin A, a specific inhibitor of Src-like
      protein tyrosine kinases, was shown to inhibit virus-induced tyrosine
      phosphorylations and to reduce the production of progeny virions. In contrast, in
      cells treated with the inhibitors staurosporine and calphostin C, the synthesis
      of progeny virions was not affected. Immunoprecipitation experiments suggested
      that the tyrosine-phosphorylated 200-kDa protein in CVB3-infected cells is of
      cellular origin. In summary, these investigations have begun to unravel the
      effect of CVB3 as well as EV11 and EV12 replication on cellular tyrosine
      phosphorylation and support the importance of tyrosine phosphorylation events for
      effective virus replication. Such cellular phosphorylation events triggered in
      the course of enterovirus infection may enhance virus replication.

PMID- 8985389
TI  - Trypsin-sensitive and -resistant components in human T-cell membranes required
      for syncytium formation by human T-cell lymphotropic virus type 1-bearing cells.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) envelope proteins play an
      important role in viral entry into target cells. In a syncytium formation assay
      consisting of a coculture of HTLV-1-bearing cells and target cells, mature gp46
      and gp21 proteins each inhibited syncytium formation induced by HTLV-1-bearing
      cells. Experiments with 125I-labeled proteins showed that 125I-gp46 bound
      specifically with MOLT-4 target cells even in the presence of large amounts of
      gp21, whereas 125I-gp21 binding to target cells was completely blocked in the
      presence of large amounts of gp46. These observations suggest that HTLV-1
      envelope proteins in syncytium formation interact with at least two components,
      which are located close to each other on the cell membrane. We isolated two
      components from MOLT-4 cell lysate, using Sepharose 4B columns coupled with
      peptides corresponding to amino acids 197 to 216 and 400 to 429, respectively, of
      the envelope protein. One is a trypsin digestion-sensitive component of
      approximately 34 to 35 kDa, which interacts specifically with gp46. The other is
      a nonprotein component, which interacts with gp21. This component was destroyed
      by sodium periodate oxidation and was partitioned into the methanol-chloroform
      phase. These observations suggest that these two components play an important
      role in HTLV-1 entry into target cells via membrane fusion.

PMID- 8985390
TI  - Support of a cucumber mosaic virus satellite RNA maps to a single amino acid
      proximal to the helicase domain of the helper virus.
AB  - Cucumber mosaic virus (CMV) is a tripartite RNA virus that can support the
      replication of satellite RNAs, small molecular parasites of the virus. Satellite
      RNAs can have a dramatic effect on the helper virus and the host plant in a
      manner specific to the helper, satellite, and host. Previously, we showed that
      the Sny-CMV strain is not able to support the replication of the WL1 satellite
      RNA in zucchini squash and that this phenotype maps to RNA 1. In the present
      study, we use recombinant cDNA clones of Fny- and Sny-CMV RNA 1 and a site
      directed mutant of Fny-CMV RNA 1 to demonstrate that the inability to support WL1
      satellite RNA maps to a single amino acid at residue 978 in the 1a protein,
      proximal to the helicase domain VI. Support of satellite RNA in whole plants and
      in protoplasts of zucchini squash is analyzed.

PMID- 8985391
TI  - Recombinational history and molecular evolution of western equine
      encephalomyelitis complex alphaviruses.
AB  - Western equine encephalomyelitis (WEE) virus (Togaviridae: Alphavirus) was shown
      previously to have arisen by recombination between eastern equine
      encephalomyelitis (EEE)- and Sindbis-like viruses (C. S. Hahn, S. Lustig, E. G.
      Strauss, and J. H. Strauss, Proc. Natl. Acad. Sci. USA 85:5997-6001, 1988). We
      have now examined the recombinational history and evolution of all viruses
      belonging to the WEE antigenic complex, including the Buggy Creek, Fort Morgan,
      Highlands J, Sindbis, Babanki, Ockelbo, Kyzylagach, Whataroa, and Aura viruses,
      using nucleotide sequences derived from representative strains. Two regions of
      the genome were examined: sequences of 477 nucleotides from the C terminus of the
      E1 envelope glycoprotein gene which in WEE virus was derived from the Sindbis
      like virus parent, and 517 nucleotide sequences at the C terminus of the nsP4
      gene which in WEE virus was derived from the EEE-like virus parent. Trees based
      on the E1 region indicated that all members of the WEE virus complex comprise a
      monophyletic group. Most closely related to WEE viruses are other New World
      members of the complex: the Highlands J, Buggy Creek, and Fort Morgan viruses.
      More distantly related WEE complex viruses included the Old World Sindbis,
      Babanki, Ockelbo, Kyzylagach, and Whataroa viruses, as well as the New World Aura
      virus. Detailed analyses of 38 strains of WEE virus revealed at least 4 major
      lineages; two were represented by isolates from Argentina, one was from Brazil,
      and a fourth contained isolates from many locations in South and North America as
      well as Cuba. Trees based on the nsP4 gene indicated that all New World WEE
      complex viruses except Aura virus are recombinants derived from EEE- and Sindbis
      like virus ancestors. In contrast, the Old World members of the WEE complex, as
      well as Aura virus, did not appear to have recombinant genomes. Using an
      evolutionary rate estimate (2.8 x 10(-4) substitutions per nucleotide per year)
      obtained from E1-3' sequences of WEE viruses, we estimated that the recombination
      event occurred in the New World 1,300 to 1,900 years ago. This suggests that the
      alphaviruses originated in the New World a few thousand years ago.

PMID- 8985392
TI  - Enhancement of in vivo adenovirus-mediated gene transfer and expression by prior
      depletion of tissue macrophages in the target organ.
AB  - Based on the hypothesis that tissue macrophages present an obstacle for
      adenovirus (Ad) vector-mediated gene transfer to internal organs, this study
      evaluated the consequences of transient depletion of Kupffer cells on subsequent
      transfer of the Ad vector genome and Ad vector-directed gene expression in the
      livers of experimental animals. Depletion of Kupffer cells in mice by intravenous
      administration of multilamellar liposomes containing dichloromethylene
      bisphosphonate permitted subsequent intravenous administration of an Ad vector to
      provide a higher input of recombinant adenoviral DNA to the liver, an absolute
      increase in transgene expression, and a delayed clearance of the vector DNA and
      transgene expression. These observations suggest that the tissue macrophages pose
      a significant hurdle to Ad vector-mediated gene transfer and that strategies to
      transiently suppress macrophage defenses might be useful in enhancing the
      efficiency of this in vivo gene transfer system.

PMID- 8985394
TI  - Bovine lentivirus induces early transient B-cell proliferation in experimentally
      inoculated cattle and appears to be pantropic.
AB  - Bovine immunodeficiency-like virus (BIV) was first isolated in 1972 (M. J.
      VanDerMaaten et al., J. Natl. Cancer Inst. 49:1649-1657, 1972). Much work has
      been done on the molecular characterization of BIV in studies using the original
      BIV R29 isolate; however, R29 is believed to be attenuated since it no longer
      causes either mononuclear cell number increases or detectable enlargement of
      lymphatic nodules in experimentally infected cattle. The host cell tropism and
      changes in host peripheral blood lymphocyte populations following infection with
      BIV are unknown. Recently, we isolated and characterized a field isolate of BIV,
      FL112 (D. L. Suarez et al., J. Virol. 67:5051-5055, 1993) that causes a
      transient, mononuclear cell lymphocytosis in experimentally infected cattle. In
      the present study, cattle were inoculated with BIV FL112, and data from flow
      cytometry showed that BIV causes a B-cell lymphocytosis with no consistent,
      significant changes in other mononuclear cell populations, including CD3+, CD4+,
      and CD8+ cells. Cell sorting and PCR amplification were used to show that BIV may
      be pantropic. Proviral DNA was present in CD3+, CD4+, CD8+, and B-cells,
      monocytes, and WC1 cells (gamma/delta T cells, null cells) by 3 to 6 days
      postinoculation and also at 2.5 years postinoculation.

PMID- 8985393
TI  - Both wild-type and strongly attenuated bovine leukemia viruses protect peripheral
      blood mononuclear cells from apoptosis.
AB  - Bovine leukemia virus (BLV) and the human T-cell leukemia viruses belong to the
      same subfamily of oncoviruses. Although much attention has focused on the
      mechanisms of cell proliferation and transformation by these viruses, experiments
      on the apoptotic process have yielded conflicting data in in vitro cell culture.
      Experimental infection of sheep with BLV proviruses offers the opportunity to
      analyze apoptosis in vivo. Here, we show that BLV-infected peripheral mononuclear
      cells, cultivated ex vivo, are protected from spontaneous programmed cell death.
      Moreover, the virus is able to specifically interfere with the apoptotic program
      of infected B lymphocytes. Strongly attenuated mutant proviruses that harbor
      deletions in the G4 and/or R3 genes also decrease the global susceptibility to
      apoptosis at levels similar to those obtained with the wild-type virus. In
      addition, cell culture supernatants from wild-type and mutant viruses can prevent
      uninfected cells from undergoing programmed cell death. These observations
      demonstrate that the R3 and G4 genes are not required to maintain both direct and
      indirect protection against apoptosis. They also imply that the level of
      programmed cell death observed ex vivo is independent of the amounts of
      proviruses in the animals. The failure of these cells to undergo apoptosis might
      be related to the pathogenesis induced by BLV.

PMID- 8985395
TI  - Mapping of a major osteomagenic determinant of murine leukemia virus RFB-14 to
      non-long terminal repeat sequences.
AB  - Certain isolates of murine leukemia viruses (MuLVs) have, apart from a
      leukemogenic potential, the capability of inducing diseases of nonhematopoietic
      tissues in susceptible strains of mice. We have reported on the molecular cloning
      of a bone-tumorigenic virus, RFB-14 MuLV, which was found to induce benign bone
      tumors, osteomas, with 100% incidence in mice of the CBA/Ca strain (L. Pedersen,
      W. Behnisch, J. Schmidt, A. Luz, F. S. Pedersen, V. Erfle, and P. G. Strauss, J.
      Virol. 66:6186-6190, 1992). In order to analyze the bone tumor-inducing phenotype
      of RFB-14 MuLV, we have studied the pathogenic potential of recombinant viruses
      between RFB-14 and the nonosteomagenic, highly leukemogenic SL3-3 MuLV. The
      recombinants were constructed so as to reveal whether a major determinant of
      osteomagenicity maps to sequences within or outside the long terminal repeats
      (LTR). Our data show that a major determinant of the osteoma-inducing potential
      of RFB-14 MuLV maps to the non-LTR region of the genome. Furthermore, we
      demonstrate that a strong determinant of leukemogenicity is harbored by the non
      LTR region of SL3-3 MuLV.

PMID- 8985396
TI  - Association of the parainfluenza virus fusion and hemagglutinin-neuraminidase
      glycoproteins on cell surfaces.
AB  - We previously observed that cell fusion caused by human parainfluenza virus type
      2 or type 3 requires the expression of both the fusion (F) and hemagglutinin
      neuraminidase (HN) glycoproteins from the same virus type, indicating that a type
      specific interaction between F and HN is needed for the induction of cell fusion.
      In the present study we have further investigated the fusion properties of F and
      HN proteins of parainfluenza virus type 1 (PI1), type 2 (PI2), and type 3 (PI3),
      Sendai virus (SN), and simian virus 5 (SV5) by expression of their glycoprotein
      genes in HeLa T4 cells using the vaccinia virus-T7 transient expression system.
      Consistent with previous results, cell fusion was observed in cells transfected
      with homotypic F/HN proteins; with one exception, coexpression of any combination
      of F and HN proteins from different viruses did not result in cell fusion. The
      only exception was found with the closely related PI1 HN and SN HN glycoproteins,
      either of which could interact with SN F to induce cell fusion upon coexpression
      as previously reported. By specific labeling and coprecipitation of proteins
      expressed on the cell surface, we observed that anti-PI2 HN antiserum
      coprecipitated PI2 F when the homotypic PI2 F and PI2 HN were coexpressed, but
      not the F proteins of other paramyxoviruses when heterotypic F genes were
      coexpressed with PI2 HN, suggesting that the homotypic F and HN proteins are
      physically associated with each other on cell surfaces. Furthermore, we observed
      that PI3 F was found to cocap with PI3 HN but not with PI2 HN, also indicating a
      specific association between the homotypic proteins. These results indicate that
      the homotypic F and HN glycoproteins are physically associated with each other on
      the cell surface and suggest that such association is crucial to cell fusion
      induced by paramyxoviruses.

PMID- 8985397
TI  - Regulated processing of hepatitis C virus core protein is linked to subcellular
      localization.
AB  - Posttranslational processing and subcellular localization of the HCV core protein
      are critical steps involved in the assembly of hepatitis C virus (HCV). In this
      study, both of these events were investigated by in vitro translation and
      transient COS-1 cell transfection of core protein expression constructs.
      Mutations at amino acid residues 173 to 174 and 191 to 192 disrupted processing
      events at the two putative cleavage sites in the C-terminal hydrophobic region of
      the core protein, indicating that these residues are implicated in the pathway of
      core protein maturation. As a result, two forms of core protein, C173 and C191,
      were detected by immunoblotting. Indirect immunofluorescence experiments showed
      that core proteins C173 and C191, when produced from HCV full-length protein or
      various polyprotein precursors, displayed a cytoplasmic localization. The C173
      species, however, was translocated to the nucleus when expressed in the absence
      of C191. These findings indicate that preferential cleavage may occur during core
      protein maturation and that the association of the C191 with the C173 species may
      contribute to the distinct subcellular distribution of core protein. This may
      provide a possible mechanism for the control of the diverse biological functions
      of core protein during HCV replication and assembly.

PMID- 8985398
TI  - Human immunodeficiency virus type 1 genetic evolution in children with different
      rates of development of disease.
AB  - The rate of development of disease varies considerably among human
      immunodeficiency virus type 1 (HIV-1)-infected children. The reasons for these
      observed differences are not clearly understood but most probably depend on the
      dynamic interplay between the HIV-1 quasispecies virus population and the immune
      constraints imposed by the host. To study the relationship between disease
      progression and genetic diversity, we analyzed the evolution of viral sequences
      within six perinatally infected children by examining proviral sequences spanning
      the C2 through V5 regions of the viral envelope gene by PCR of blood samples
      obtained at sequential visits. PCR product DNAs from four sample time points per
      child were cloned, and 10 to 13 clones from each sample were sequenced. Greater
      genetic distances relative to the time of infection were found for children with
      low virion-associated RNA burdens and slow progression to disease relative to
      those found for children with high virion-associated RNA burdens and rapid
      progression to disease. The greater branch lengths observed in the phylogenetic
      reconstructions correlated with a higher accumulation rate of nonsynonymous base
      substitutions per potential nonsynonymous site, consistent with positive
      selection for change rather than a difference in replication kinetics. Viral
      sequences from children with slow progression to disease also showed a tendency
      to form clusters that associated with different sampling times. These progressive
      shifts in the viral population were not found in viral sequences from children
      with rapid progression to disease. Therefore, despite the HIV-1 quasispecies
      being a diverse, rapidly evolving, and competing population of genetic variants,
      different rates of genetic evolution could be found under different selective
      constraints. These data suggest that the evolutionary dynamics exhibited by the
      HIV-1 quasispecies virus populations are compatible with a Darwinian system
      evolving under the constraints of natural selection.

PMID- 8985399
TI  - Virus-specific memory and effector T lymphocytes exhibit different cytokine
      responses to antigens during experimental murine respiratory syncytial virus
      infection.
AB  - Mice sensitized to the G (attachment) or F (fusion) glycoproteins of respiratory
      syncytial virus (RSV) expressed different patterns of cytokine production and
      lung pathology when challenged by intranasal infection with RSV. Five days after
      challenge, mice sensitized to G glycoprotein produced high levels of interleukin
      4 (IL-4) and IL-5 in the lungs and spleens and developed extensive pulmonary
      eosinophilia, while mice sensitized to F glycoprotein produced IL-2 and developed
      a mononuclear cell infiltration. Memory lymphocytes isolated 2 weeks after
      intranasal challenge of mice primed to the G or F glycoprotein secreted only IL-2
      and gamma interferon (IFN-gamma) when stimulated with RSV. IL-4 and IL-5
      production characteristic of Th2-type effectors in the lung was observed only
      after multiple rounds of in vitro stimulation of RSV G-specific memory T
      lymphocytes with antigen. Also IFN-gamma production appeared to play only a minor
      role in the expression of pulmonary pathology characteristic of Th1 or Th2 T
      lymphocyte responses, because mice genetically deficient in IFN-gamma production
      by gene disruption displayed the same pattern of pulmonary inflammation to RSV
      infection after priming to RSV F or G as conventional mice. These results suggest
      that effector T lymphocytes exhibit a different pattern of cytokine production
      than memory T-lymphocyte precursors precommitted to a Th1 or Th2 pattern of
      differentiation. Furthermore, these observations raise the possibility that the
      cytokine response of human memory T lymphocytes after a single exposure to
      antigen in vitro may not accurately reflect the cytokine response of
      differentiated effector T lymphocytes at the site of infection in vivo.

PMID- 8985400
TI  - Kissing of the two predominant hairpin loops in the coxsackie B virus 3'
      untranslated region is the essential structural feature of the origin of
      replication required for negative-strand RNA synthesis.
AB  - Higher-order RNA structures in the 3' untranslated region (3'UTR) of
      enteroviruses are thought to play a pivotal role in viral negative-strand RNA
      synthesis. The structure of the 3'UTR was predicted by thermodynamic calculations
      using the STAR (structural analysis of RNA) computer program and experimentally
      verified using chemical and enzymatic probing of in vitro-synthesized RNA. A
      possible pseudoknot interaction between the 3D polymerase coding sequence and
      domain Y and a "kissing" interaction between domains X and Y was further studied
      by mutational analysis, using an infectious coxsackie B3 virus cDNA clone (domain
      designation as proposed by E. V. Pilipenko, S. V. Maslova, A. N. Sinyakov, and
      V.I. Agol (Nucleic Acids Res. 20:1739-1745, 1992). The higher-order RNA structure
      of the 3'UTR appeared to be maintained by an intramolecular kissing interaction
      between the loops of the two predominant hairpin structures (X and Y) within the
      3'UTR. Disturbing this interaction had no effect on viral translation and
      processing of the polyprotein but exerted a primary effect on viral replication,
      as was demonstrated in a subgenomic coxsackie B3 viral replicon, in which the
      capsid P1 region was replaced by the luciferase gene. Mutational analysis did not
      support the existence of the pseudoknot interaction between hairpin loop Y and
      the 3D polymerase coding sequence. Based on these experiments, we constructed a
      three-dimensional model of the 3'UTR of coxsackie B virus that shows the kissing
      interaction as the essential structural feature of the origin of replication
      required for its functional competence.

PMID- 8985401
TI  - Formation of native hepatitis C virus glycoprotein complexes.
AB  - The hepatitis C virus (HCV) glycoproteins (E1 and E2) interact to form a
      heterodimeric complex, which has been proposed as a functional subunit of the HCV
      virion envelope. As examined in cell culture transient-expression assays, the
      formation of properly folded, noncovalently associated E1E2 complexes is a slow
      and inefficient process. Due to lack of appropriate immunological reagents, it
      has been difficult to distinguish between glycoprotein molecules that undergo
      productive folding and assembly from those which follow a nonproductive pathway
      leading to misfolding and aggregation. Here we report the isolation and
      characterization of a conformation-sensitive E2-reactive monoclonal antibody
      (H2). The H2 monoclonal antibody selectively recognizes slowly maturing E1E2
      heterodimers which are noncovalently linked, protease resistant, and no longer
      associated with the endoplasmic reticulum chaperone calnexin. This complex
      probably represents the native prebudding form of the HCV glycoprotein
      heterodimer. Besides providing a novel reagent for basic studies on HCV virion
      assembly and entry, this monoclonal antibody should be useful for optimizing
      production and isolation of native HCV glycoprotein complexes for serodiagnostic
      and vaccine applications.

PMID- 8985402
TI  - Expression of Aleutian mink disease parvovirus capsid proteins in defined
      segments: localization of immunoreactive sites and neutralizing epitopes to
      specific regions.
AB  - The capsid proteins of the ADV-G isolate of Aleutian mink disease parvovirus
      (ADV) were expressed in 10 nonoverlapping segments as fusions with maltose
      binding protein in pMAL-C2 (pVP1, pVP2a through pVP2i). The constructs were
      designed to capture the VP1 unique sequence and the portions analogous to the
      four variable surface loops of canine parvovirus (CPV) in individual fragments
      (pVP2b, pVP2d, pVP2e, and pVP2g, respectively). The panel of fusion proteins was
      immunoblotted with sera from mink infected with ADV. Seropositive mink infected
      with either ADV-TR, ADV-Utah, or ADV-Pullman reacted preferentially against
      certain segments, regardless of mink genotype or virus inoculum. The most
      consistently immunoreactive regions were pVP2g, pVP2e, and pVP2f, the segments
      that encompassed the analogs of CPV surface loops 3 and 4. The VP1 unique region
      was also consistently immunoreactive. These findings indicated that infected mink
      recognize linear epitopes that localized to certain regions of the capsid protein
      sequence. The segment containing the hypervariable region (pVP2d), corresponding
      to CPV loop 2, was also expressed from ADV-Utah. An anti-ADV-G monoclonal
      antibody and a rabbit anti-ADV-G capsid antibody reacted exclusively with the ADV
      G pVP2d segment but not with the corresponding segment from ADV-Utah. Mink
      infected with ADV-TR or ADV-Utah also preferentially reacted with the pVP2d
      sequence characteristic of that virus. These results suggested that the loop 2
      region may contain a type-specific linear epitope and that the epitope may also
      be specifically recognized by infected mink. Heterologous antisera were prepared
      against the VP1 unique region and the four segments capturing the variable
      surface loops of CPV. The antisera against the proteins containing loop 3 or loop
      4, as well as the anticapsid antibody, neutralized ADV-G infectivity in vitro and
      bound to capsids in immune electron microscopy. These results suggested that
      regions of the ADV capsid proteins corresponding to surface loops 3 and 4 of CPV
      contain linear epitopes that are located on the external surface of the ADV
      capsid. Furthermore, these linear epitopes contain neutralizing determinants.
      Computer comparisons with the CPV crystal structure suggest that these sequences
      may be adjacent to the threefold axis of symmetry of the viral particle.

PMID- 8985403
TI  - Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle)
      tumor cells.
AB  - The recent discovery of DNA sequences of a new human herpesvirus in Kaposi's
      sarcoma (KS) has fueled speculation that this virus might cause KS. The mere
      presence, however, of a virus in a complex multicellular tumor like KS could just
      as well be construed as evidence of a passenger agent. We sought stronger
      evidence linking the KS-associated herpesvirus (KSHV) to tumor formation by using
      in situ hybridization to investigate the specificity, constancy, and timing of
      KSHV gene expression in KS tumor cells. Here we document expression of a 700
      nucleotide viral RNA in every KS tumor examined, from the earliest histologically
      recognizable stage to advanced tumors in which the vast majority of identifiable
      spindle tumor cells contain this transcript. Two other KSHV RNAs were also
      detected in a smaller fraction of the tumor cells in all but the earliest lesion.
      These viral RNAs were expressed to relatively low levels in this subset; because
      one of these RNAs encodes a major viral capsid protein, these cells may be
      producing KSHV. We did not find these KSHV genes expressed in a variety of other
      tumors and proliferative processes, but we did detect viral gene expression in
      prostatic tissue, supporting a possible mechanism for sexual transmission of
      KSHV. The close relationship between KS and KSHV gene expression is consistent
      with the hypothesis that KSHV is directly involved in the etiology and
      pathogenesis of KS.

PMID- 8985404
TI  - Toward highly efficient cell-type-specific gene transfer with retroviral vectors
      displaying single-chain antibodies.
AB  - Recently, we constructed retroviral vector particles derived from spleen necrosis
      virus (SNV) that display a single-chain antibody (scA) on the viral surface. By
      transient transfection protocols, we showed that such particles are competent for
      infection and cell type specific. Efficient infection was dependent on the
      presence of wild-type envelope, although wild-type SNV was not infectious on
      target cells (T.-H. T. Chu and R. Dornburg, J. Virol. 69:2659-2663, 1995; T.-H.
      T. Chu, I. Martinez, W. C. Sheay, and R. Dornburg, Gene Ther. 1:292-299, 1994).
      In this study, stable packaging lines were constructed and detailed biological
      and biochemical studies were performed. Chimeric scA-envelope fusion proteins
      were expressed as efficiently as wild-type envelope and were stable over a period
      of at least 6 h. Only a fully functional wild-type envelope could act as a helper
      for efficient virus penetration. The ratio of wild-type envelope protein to
      chimeric envelope protein appears to determine the efficiency of infection. Virus
      titers of targeting vectors obtained from stable packaging lines were as high as
      10(4) CFU/ml. A 25-fold concentration of vector virus stocks resulted in a 200
      fold increase in virus titers (up to 10(6) CFU/ml). These data indicate that an
      inhibitor of infection was (at least partially) removed by the concentration
      protocol. Our data show that this technology has several variables for further
      improvements and, therefore, has the potential to become a powerful tool for cell
      type-specific in vivo human gene therapy.

PMID- 8985405
TI  - Primer tRNA3Lys on the viral genome exists in unextended and two-base extended
      forms within mature human immunodeficiency virus type 1.
AB  - In human immunodeficiency virus type 1, tRNALys3 is placed upon the primer
      binding site, where it serves as the primer for reverse transcription. We show
      herein that genomic placement occurs independently of precursor protein
      processing and that the placed tRNALys3 exists in two major forms: unextended or
      in a form extended by the first two DNA bases incorporated, C and T. The two-base
      extended form of the tRNALys3 is absent in a protease-negative mutant, indicating
      a requirement for mature viral proteins to initiate reverse transcription within
      the virus.

PMID- 8985406
TI  - Theiler's murine encephalomyelitis virus subgroup strain-specific infection in a
      murine macrophage-like cell line.
AB  - We compared infection of a murine macrophage-like cell line, J774-1, with two
      Theiler's murine encephalomyelitis virus subgroup strains. The GDVII strain,
      which is highly virulent and produces acute polioencephalomyelitis in mice, did
      not actively replicate in J774-1 cells, although there was a significant
      inhibition in cellular protein synthesis. In contrast, the DA strain, which is
      less virulent and causes demyelination with a persistent virus infection,
      productively infected J774-1 cells; however, there was less virus produced than
      in BHK-21 cells, and there was little if any cellular protein shutoff. These in
      vitro data may provide some explanation for the biological activities that are
      observed between both subgroup strains.

PMID- 8985407
TI  - Interspecies aminopeptidase-N chimeras reveal species-specific receptor
      recognition by canine coronavirus, feline infectious peritonitis virus, and
      transmissible gastroenteritis virus.
AB  - We report that cells refractory to canine coronavirus (CCV) and feline infectious
      peritonitis virus (FIPV) became susceptible when transfected with a chimeric
      aminopeptidase-N (APN) cDNA containing a canine domain between residues 643 and
      841. This finding shows that APN recognition by these viruses is species related
      and associated with this C-terminal domain. The human/canine APN chimera was also
      able to confer susceptibility to the porcine transmissible gastroenteritis virus
      (TGEV), whereas its human/porcine homolog failed to confer susceptibility to CCV
      and FIPV. A good correlation was observed between the capacity of CCV, FIPV, and
      TGEV to recognize the different interspecies APN chimeras and their ability to
      infect cells derived from the relevant species. As an exception, TGEV was found
      to use a human/bovine APN chimera as a receptor although itself unable to
      replicate in bovine cells.

PMID- 8985408
TI  - Fusion of bovine leukemia virus with target cells monitored by R18 fluorescence
      and PCR assays.
AB  - PCR and R18 fluorescence dequenching assays have been combined to monitor the
      kinetics of fusion of bovine leukemia virus with target cells (CC81, OVK, or
      Raji). Antibodies raised against gp51 allow us to demonstrate that not only the
      hydrophobic N-terminal domain of the transmembrane glycoprotein gp30 but also
      specific domains of gp51 (amino acids 39 to 103) are involved in bovine leukemia
      virus-cell fusion.

PMID- 8985409
TI  - The cellular stress response enhances human T-cell lymphotropic virus type 1
      basal gene expression through the core promoter region of the long terminal
      repeat.
AB  - Viral protein expression is postulated to play a critical role in the
      pathogenesis of human T-cell lymphotropic virus type 1 (HTLV-1)-associated
      diseases. Therefore, knowledge of the cellular events which initiate or enhance
      viral gene expression is important in understanding the mechanism of HTLV-1
      induced disease. In this report, we examined the modulation of transcription of
      the HTLV-1 long terminal repeat (LTR) following induction of the cellular stress
      response. We demonstrate by both in vitro transcription assays and transient
      transfections that induction of the stress response increases basal transcription
      from the LTR. Transient cotransfection assays indicate that stress induction of
      viral transcription is Tax independent. In addition, we provide evidence that the
      sequences responsible for the enhanced transcription are -52 through +157 of the
      U3/R region of the HTLV-1 LTR. Finally, our data suggest that the increase in
      transcription is mediated through an intermediate polymerase II/polymerase III
      transcriptional complex, demonstrated by the inability to abolish the effect with
      low concentrations of alpha-amanitin.

PMID- 8985410
TI  - Clonal expansion of superantigen-reactive T cells is resistant to FK506 in mice
      with AIDS.
AB  - Subcutaneous injection of FK506 (10 mg/kg of body weight) completely blocked the
      clonal expansion of staphylococcal enterotoxin A (SEA)-reactive T cells in
      healthy (control) mice after SEA injection but did not disturb it in mice with
      murine AIDS (MAIDS) caused by infection with LP-BM5 murine leukemia virus. MAIDS
      mice are characterized by utilization of a FK506-insensitive pathway for clonal
      expansion of superantigen-reactive T cells.

PMID- 8985411
TI  - Susceptibility of nude mice carrying the Fv-4 gene to Friend murine leukemia
      virus infection.
AB  - Fv-4 is a mouse gene that dominantly confers resistance to infection with Friend
      murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-478, 1975).
      Despite complete resistance to ecotropic MuLV infection in mice carrying the Fv-4
      gene, it is known that cells carrying the resistance gene in tissue culture do
      not always show resistance as extensive as that in vivo (H. Yoshikura and T.
      Odaka, JNCI 61:461-463, 1978). To investigate the immunological effect on
      resistance in vivo, we introduced the Fv-4 gene into BALB/c nude mice (Fv-4-/-
      nude[nu/nu]) by mating them with Fv-4 congenic BALB/c mice (Fv-4r/r nude+/+) and
      examined the susceptibility of the F2 progeny to F-MuLV. All BALB/c nude mice
      without the Fv-4 gene (Fv-4-/- nude[nu/nu]) were permissive to F-MuLV and
      developed erythroleukemia within 2 weeks after virus inoculation. The BALB/c nude
      mice with the Fv-4 gene (Fv-4r/r nude[nu/nu]) did not develop leukemia, and no or
      little virus was detected in the spleen 7 weeks after virus inoculation. The
      resistance to F-MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F1 mice
      with the Fv-4r/- nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x
      BALB/c) F1 mice with the Fv-4r/- nude+/+ genotype. However, almost all BALB/c
      nude mice with the Fv-4r/- nude(nu/nu) genotype developed the disease within 7
      weeks, and the virus was detected in all of their spleens even in the mice
      without leukemia. These results show that the resistance caused by the Fv-4 gene
      is recessive in nude mice and dominant in BALB/c mice. Some immunological
      effects, perhaps cell-mediated immunity, may play important roles in the
      resistance to F-MuLV infection in vivo in addition to the dosage effect of the Fv
      4 product.

PMID- 8985412
TI  - Antibody prevents the establishment of persistent arenavirus infection in synergy
      with endogenous T cells.
AB  - A cardinal feature of the biology of lymphocytic choriomeningitis virus (LCMV) is
      its ability to establish persistent infections in mice. Persistence is usually
      established by infection of the mouse during the in utero or neonatal period.
      Susceptibility can be extended to the adult by treatment with immunosuppressive
      agents or by infection with immunosuppressive strains of LCMV. In this study we
      investigated the capacity of passively acquired anti-LCMV antibodies to prevent
      the establishment of persistence in both neonatal and adult mice. Suckling BALB/c
      mouse pups nursed by mothers immunized against LCMV before pregnancy had higher
      survival rates following infection than controls and withstood challenge doses of
      up to 400 PFU without becoming persistently infected. To establish that maternal
      antibody alone and not maternally derived T cells provided this protection,
      nonimmune mothers were infused with monoclonal anti-LCMV neutralizing antibodies
      within 24 h after delivering their pups. Pups nursing on these passively
      immunized mothers were resistant to persistent LCMV infection. The establishment
      of persistence in adult BALB/c mice by the immunosuppressive, macrophage-tropic
      LCMV variant, clone 13 was also prevented by prophylactic treatment with anti
      LCMV monoclonal antibodies. However, the protection afforded by passively
      acquired antibody was found to be incomplete if the recipients lacked functional
      CD8+ T cells. While 65% of neonatal athymic (nu/nu) mice nursed by immune nu/+
      dams resisted low-dose viral challenge (25 PFU), the majority of nude pups
      challenged with high doses of virus (100 PFU) became persistently infected. Also,
      protection was incomplete in beta2-microglobulin knockout mice, which lack
      functional CD8+ T cells, suggesting that a cooperative effect was exerted by the
      combination of neutralizing antibody and endogenous T cells. These results
      indicate that antibodies provide an effective barrier to the establishment of
      persistent infections in immunocompetent mice and reaffirm that vaccines which
      induce strong humoral responses may provide efficient protection against
      arenavirus infections.

PMID- 8985413
TI  - Length polymorphism within the second variable region of the human
      immunodeficiency virus type 1 envelope glycoprotein affects accessibility of the
      receptor binding site.
AB  - Sequential mutations were introduced into the V2 region of human immunodeficiency
      virus (HIV) type 1 HXB2, affecting the length, charge, and number of potential
      glycosylation sites. The insertions had no effect on cytopathicity or on the
      ability of virus to replicate in peripheral blood mononuclear cells and
      established T-cell lines. However, deletion of amino acids 186 to 188, encoding a
      conserved glycosylation site, resulted in a nonviable virus, suggesting a minimal
      length requirement of 40 amino acids for a functional V2 loop. However, all amino
      acid insertions affected the sensitivity of the variants to neutralization by
      soluble CD4 and monoclonal antibodies specific for epitopes in the V3 and CD4
      binding site regions. Furthermore, these mutant viruses showed resistance to
      neutralization by HIV-positive human sera. Soluble gp120 mutant glycoproteins
      showed increased affinities for soluble CD4 and monoclonal antibodies specific
      for a number of epitopes overlapping the CD4 binding site, confirming that length
      increases in V2 affect exposure of the CD4 binding site. In summary, these data
      demonstrate that differences in V2 length modulate immunoreactivity of the
      envelope glycoprotein and support an association between the V2 and CD4 binding
      site regions.

PMID- 8985414
TI  - Identification of a cytoplasmic Tyr-X-X-Leu motif essential for down regulation
      of the human cell receptor CD46 in persistent measles virus infection.
AB  - To investigate the sequence requirements for measles virus (MV)-induced receptor
      down regulation, we transfected the human CD46 gene into simian cells
      persistently infected by the Biken strain of MV. Surface expression of CD46 is
      drastically reduced in these cells. Deletion analysis has shown that the
      juxtamembrane region of the CD46 cytoplasmic domain is essential for down
      regulation. Deleting a Tyr-Arg-Tyr-Leu sequence in this region or changing these
      residues to Ala prevents CD46 down regulation from the infected cell surface.
      Alanine-scanning mutagenesis has identified two amino acid residues, Tyr and Leu,
      forming a Tyr-X-X-Leu motif critical for CD46 down regulation. Mutations that
      prevent CD46 down regulation enhance syncytium formation. These results indicate
      that CD46 down regulation limits the cytopathic effects in a persistent MV
      infection and that CD46 down regulation requires a cytoplasmic Tyr-X-X-Leu
      sequence which resembles known motifs for membrane protein trafficking and
      receptor signalling.

PMID- 8985415
TI  - STAT1 pathway is involved in activation of caprine arthritis-encephalitis virus
      long terminal repeat in monocytes.
AB  - The caprine arthritis-encephalitis virus (CAEV) long terminal repeat (LTR) is
      activated by gamma interferon (IFN-gamma) in promonocytic cells. We have
      previously shown that a 70-bp element is necessary and sufficient for the
      response of the CAEV LTR to this cytokine. At the 5' end, this 70-bp IFN-gamma
      response element contains sequence similarity to the gamma activated site (GAS).
      Here we demonstrate that the putative GAS element in the CAEV LTR binds
      specifically to a cellular factor induced by IFN-gamma in promonocytic cells.
      Substitution mutations in this consensus sequence eliminate binding of the
      inducible factor. The GAS element from the 70-bp motif is sufficient to confer
      responsiveness to IFN-gamma using a heterologous minimal promoter. Consistent
      with the binding data, the same mutations in the GAS element eliminate
      responsiveness to IFN-gamma in the context of both a functional CAEV LTR and a
      heterologous promoter. The cellular factor that binds to the GAS element is
      present from 5 min to 14 h after stimulation with IFN-gamma. Binding of the
      nuclear factor to the GAS element in the CAEV LTR is inhibited by antibody
      directed against STAT1 (p91/84). Thus, the GAS sequence in the CAEV LTR is
      essential for the response to IFN-gamma and a STAT1-like factor binds to this
      site. The STAT-1 signaling pathway provides at least one mechanism for activation
      of the CAEV LTR by IFN-gamma in monocytes. These data are the first demonstration
      of a role for a STAT family member in the regulation of a viral promoter.

PMID- 8985417
TI  - Mouse cells expressing human intercellular adhesion molecule-1 are susceptible to
      infection by coxsackievirus A21.
AB  - Competitive viral binding assays have revealed previously that coxsackievirus A21
      (CAV21) and human rhinovirus 14 (HRV14) share a common cell surface receptor.
      More recently, intercellular adhesion molecule-1 (ICAM-1) has been identified as
      the cellular receptor for HRV-14. Also, anti-ICAM-1 monoclonal antibodies (MAbs)
      blocked infection by HRV14, CAV13, CAV18, and CAV21, suggesting that these
      viruses share this receptor; however, this has never been established by more
      direct methods. In this study we show conclusively that CAV21 binds to ICAM-1 and
      that MAbs directed against the N-terminal domain of the molecule inhibit this
      attachment. Furthermore, we show that the specific interaction between ICAM-1 and
      160S CAV21 virions induces formation of 135S A particles. Finally, we show
      transfection of normally nonsusceptible mouse L cells with human ICAM-1 cDNA
      renders them susceptible to infection by CAV21.

PMID- 8985418
TI  - The N-terminal region of hepatitis C virus-encoded NS5A is important for NS4A
      dependent phosphorylation.
AB  - We previously showed that two proteins, a 56-kDa protein (p56) and a 58-kDa
      protein (p58), are produced from the hepatitis C virus (HCV) nonstructural 5A
      region (NS5A) and that the production of p58 is enhanced by the presence of NS4A
      (T. Kaneko, Y. Tanji, S. Satoh, M. Hijikata, S. Asabe, K. Kimura, and K.
      Shimotohno, Biochem. Biophys. Res. Commun. 205:320-326, 1994). Both proteins have
      phosphorylated serine residues, some of which are located in the C-terminal
      region. In p58, phosphorylation of serine residues in the central region of HCV
      NS5A is important for production of p58 in an NS4A-dependent manner. To clarify
      the mechanism of NS5A phosphorylation, in particular phosphorylation in the
      central region, phosphorylation of deleted and mutated forms of NS5A was analyzed
      using a transient protein production system in cultured cells in the presence or
      absence of NS4A. Association of the NS5A region from amino acids 2135 to 2139
      with NS4A was important for NS4A-dependent phosphorylation of NS5A.

PMID- 8985419
TI  - In vivo administration of interleukin-2 protects susceptible mice from Theiler's
      virus persistence.
AB  - In vivo administration of interleukin-2 (IL-2)-secreting tumor cells results in
      complete protection against persistent infection by Theiler's murine
      encephalomyelitis virus (TMEV) in susceptible DBA/2 mice. The IL-2-mediated
      protection was found to depend on the inoculum size as well as the timing of IL-2
      administration. IL-2-treated and TMEV-infected mice displayed a three- to
      fourfold relative increase in virus-specific cytotoxic T-lymphocyte (CTL)
      precursors. Thus, we postulate that the persistence of TMEV infection in
      susceptible mice reflects limited numbers of relevant CTL precursors and their
      time course of induction and activation.

PMID- 8985416
TI  - A sorting motif localizes the foamy virus glycoprotein to the endoplasmic
      reticulum.
AB  - We recently identified an endoplasmic reticulum (ER) retrieval signal-the
      dilysine motif-in the glycoproteins of all five foamy viruses (FVs) for which
      sequences were available (P. A. Goepfert, G. Wang, and M. J. Mulligan, Cell
      82:543-544, 1995). In the present study, expression of recombinant human FV (HFV)
      glycoprotein and analyses of oligosaccharide modifications and precursor cleavage
      indicated that the protein was localized to the ER. HFV glycoproteins encoding
      seven different dilysine motif mutations were then expressed. The results
      indicated that disruptions of the dilysine motif resulted in higher levels of
      forward transport of the HFV glycoprotein from the ER through the Golgi apparatus
      to the plasma membrane. We conclude that the dilysine motif is responsible for ER
      sorting of the FV glycoprotein. Signal-mediated ER localization has not
      previously been described for a retroviral glycoprotein.

PMID- 8985420
TI  - Infection of primary cultures of human neural cells by human coronaviruses 229E
      and OC43.
AB  - We evaluated the ability of human coronaviruses to infect primary cultures of
      human neural cells. Double immunofluorescence with antibodies to virus and cell
      markers showed infection of fetal astrocytes and of adult microglia and
      astrocytes by strain OC43. RNA amplification revealed infection of fetal
      astrocytes, adult microglia, and a mixed culture of adult oligodendrocytes and
      astrocytes by strain 229E. Infectious virus was released only from fetal
      astrocytes, with higher titers for OC43. Human coronaviruses have the capacity to
      infect some cells of the central nervous system, although infection of adult
      cells appears abortive.

PMID- 8985421
TI  - Equivalent inhibition of half-site and full-site retroviral strand transfer
      reactions by structurally diverse compounds.
AB  - In vitro assay systems which use recombinant retroviral integrase (IN) and short
      DNA oligonucleotides fail to recapitulate the full-site integration reaction as
      it is known to occur in vivo. The relevance of using such circumscribed in vitro
      assays to define inhibitors of retroviral integration has not been formerly
      demonstrated. Therefore, we analyzed a series of structurally diverse inhibitors
      with respect to inhibition of both half-site and full-site strand transfer
      reactions with either recombinant or virion-produced IN. Half-site and full-site
      reactions catalyzed by avian myeloblastosis virus and human immunodeficiency
      virus type 1 (HIV-1) IN from virions are shown to be equivalently sensitive to
      inhibition by compounds which inhibit half-site reactions catalyzed by the
      recombinant HIV-1 IN. These studies therefore support the utility of using in
      vitro assays employing either recombinant or virion-derived IN to identify
      inhibitors of integration.

PMID- 8985422
TI  - Mapping the multimerization domains of the Gag protein of yeast retrotransposon
      Ty1.
AB  - The two-hybrid system was used to define regions of the Ty1 Gag protein
      responsible for multimerization. Gag truncations lacking the first 146 or the
      last 97 amino acids (Gag is 440 amino acids in length) interact. A severely C
      terminally truncated molecule (lacking the last 207 amino acids) was the smallest
      truncation to interact, suggesting that some protein-protein interactions between
      Gag molecules are mediated through the first 233 amino acids. However, an
      internal deletion of amino acids 147 to 233 does not abolish Gag-Gag interaction,
      indicating that more than one region can mediate Gag interaction. Surprisingly,
      we found that a truncation lacking the last 97 amino acids interacts with itself
      but not with full-length Gag. This is apparently due to an artifact of the two
      hybrid assay, since these same molecules coassemble with wild-type Gag into Ty1
      virus-like particles.

PMID- 8985423
TI  - Efficient multiplication of a Semliki Forest virus chimera containing Sindbis
      virus spikes.
AB  - Using the Semliki Forest virus (SFV) and Sindbis virus (SIN) cDNAs we have
      constructed recombinants in which the spike genes were exchanged. Analyses of
      expression showed that the SFV/SIN(spike) RNA directed efficient assembly of
      infectious virus, whereas the reciprocal SIN/SFV(spike) RNA was completely unable
      to assemble virus. This was apparently due to a defective capsid-spike
      interaction.

PMID- 8985425
TI  - Sequences flanking the core DNA-binding domain of bovine papillomavirus type 1 E2
      contribute to DNA-binding function.
AB  - We have compared a series of molecular constructs that contain the minimal DNA
      binding and dimerization domain of bovine papillomavirus type 1 (BPV-1) E2 alone
      or this binding domain plus the adjacent 16 or 40 amino acids to test the role of
      the flanking sequences in E2 function. The presence of these sequences resulted
      in an up to eightfold increase in the affinity of E2 for its target DNA and
      stabilized the protein against denaturation both in the absence of DNA and in the
      form of DNA-protein complexes. In addition, an aspartic acid-to-tyrosine mutation
      within the flanking region blocked DNA binding and function. These data
      demonstrate that sequences flanking the core domain contribute to E2 function and
      are, in fact, an integral part of the DNA-binding domain of BPV-1 E2.

PMID- 8985424
TI  - Murine coronavirus packaging signal confers packaging to nonviral RNA.
AB  - Studies of defective interfering (DI) RNAs of the murine coronavirus mouse
      hepatitis virus (MHV) suggest that a 69-nucleotide-long packaging signal is
      necessary for MHV genomic RNA packaging into MHV particles. In this study we
      showed that when RNA transcripts that consisted of a non-MHV sequence and the
      packaging signal were expressed in MHV-infected cells, they were packaged into
      MHV particles. Those RNA transcripts that lacked the packaging signal or those
      containing a mutated packaging signal did not package efficiently. Thus, the
      presence of the packaging signal was sufficient for RNA packaging into MHV
      particles.

PMID- 8985426
TI  - Protection of mice from respiratory Sendai virus infections by recombinant
      vaccinia viruses.
AB  - Mechanisms of protection of mice from Sendai virus, which is exclusively
      pneumotropic and causes a typical respiratory disease, by immunization with
      recombinant vaccinia viruses (RVVs) were investigated. Although the RVV carrying
      a hemagglutinin-neuraminidase gene of Sendai virus (Vac-HN) propagated in the
      noses and lungs of mice by either intranasal (i.n.) or intraperitoneal (i.p.)
      inoculation, no vaccinia virus antigens were detected in the mucosal layer of
      upper and lower airways of the i.p.-inoculated mice. The mice immunized i.n. with
      Vac-HN or Vac-F (the RVV carrying a fusion protein gene of Sendai virus)
      demonstrated the strong resistance to Sendai virus challenge both in the lung and
      in the nose, whereas the i.p.-immunized mice showed almost no resistance in the
      nose but showed a partial resistance in the lung. Titration of Sendai virus
      specific antibodies in the nasal wash (NW), bronchoalveolar lavage (BAL), and
      serum collected from the Vac-F-immunized mice showed that the NW from the i.n.
      immunized mice contained immunoglobulin A (IgA) antibodies but no IgG and the BAL
      from the mice contained both IgA and IgG antibodies. On the other hand, neither
      IgA nor IgG antibodies were detected in the NW from the i.p.-immunized mice and
      only IgG antibodies were detected in the BAL, although both i.n.- and i.p.
      immunized mice exhibited similar levels of serum IgG, IgA, and neutralizing
      antibodies. The resistance to Sendai virus in the noses of i.n.-immunized mice
      could be abrogated by the intranasal instillation of anti-mouse IgA but not of
      anti-IgG antiserum, while the resistance in the lung was not significantly
      abrogated by such treatments. These results demonstrate that IgA is a major
      mediator for the immunity against Sendai virus induced by the RVVs and IgG is a
      supplementary one, especially in the lung, and that the RVV should be
      intranasally inoculated to induce an efficient mucosal immunity even if it has a
      pantropic nature.

PMID- 8985427
TI  - Human herpesvirus 8 encodes a homolog of interleukin-6.
AB  - Kaposi's sarcoma is a multifocal lesion that is reported to be greatly influenced
      by cytokines such as interleukin-6 (IL-6) and oncostatin M. DNA sequences of a
      novel human gammaherpesvirus, termed human herpesvirus 8 (HHV-8) or Kaposi
      sarcoma-associated herpesvirus, have been identified in all epidemiological forms
      of Kaposi's sarcoma with high frequency. The presence of HHV-8 DNA is also
      clearly associated with certain B-cell lymphomas (body cavity-based lymphomas)
      and multicentric Castleman's disease. Sequence analysis of a 17-kb fragment
      revealed that adjacent to a block of conserved herpesvirus genes (major DNA
      binding protein, glycoprotein B, and DNA polymerase), the genome of HHV-8 encodes
      structural homolog of IL-6. This cytokine is involved not only in the
      pathogenesis of Kaposi's sarcoma but also in certain B-cell lymphomas and
      multicentric Castleman's disease. The viral counterpart of IL-6 (vIL-6) has
      conserved important features such as cysteine residues involved in disulfide
      bridging or an amino-terminal signal peptide. Most notably, the region known to
      be involved in receptor binding is highly conserved in vIL-6. This conservation
      of essential features and the remarkable overlap between diseases associated with
      HHV-8 and diseases associated with IL-6 disregulation clearly suggest that vIL-6
      is involved in HHV-8 pathogenesis.

PMID- 8985429
TI  - Isolation of an amino-terminal region of bovine papillomavirus type 1 E1 protein
      that retains origin binding and E2 interaction capacity.
AB  - In vitro DNA binding results from a series of E1 proteins containing amino
      terminal or carboxy-terminal truncations indicated that sequences between amino
      acids 121 and 284 were critical for origin binding. Additional binding
      experiments with E1 proteins containing internal, in-frame insertions or
      deletions confirmed the importance of the region defined by truncated E1 proteins
      and also demonstrated that downstream sequences were not required for binding
      activity in the context of the full-length E1 protein. On the basis of mapping
      results from the E1 mutants, a clone (pE1(121-311)) was constructed that
      expressed E1 amino acids within the approximate boundaries of the critical
      sequences for DNA binding. The E1(121-311) protein retained origin-specific DNA
      binding, confirming that this region was not only necessary but was also
      sufficient for origin recognition. In addition to origin binding, E1(121-311)
      bound E2 protein in a cold-sensitive manner. Therefore, DNA binding and E2
      binding activities colocalize to a 191-amino-acid functional domain derived from
      the amino-terminal half of the E1 protein. Finally, three E1 proteins with
      mutations in this region all lacked DNA binding activity and were all defective
      for in vivo replication. Two of these E1 mutants retained E2 binding capability,
      demonstrating that origin recognition by E1 is critical for replication and
      cannot necessarily be rescued by an interaction with E2 protein.

PMID- 8985428
TI  - Subcellular localization of avian sarcoma virus and human immunodeficiency virus
      type 1 integrases.
AB  - The composition and subcellular trafficking of subviral preintegration complexes
      are reported to vary among the different retroviruses. The process by which the
      avian sarcoma virus (ASV) preintegration complex gains access to target chromatin
      remains unknown. Here we report that ASV integrase (IN) expressed as a fusion to
      beta-galactosidase accumulates in the nuclei of transfected COS-1 cells. In
      contrast, human immunodeficiency type 1 (HIV-1) IN-beta-galactosidase fusions
      expressed similarly are predominantly cytoplasmic. To identify the region of ASV
      IN that specifies nuclear localization, various subdomains of the protein were
      expressed as beta-galactosidase fusions and their subcellular locations were
      assessed cytochemically and by indirect immunofluorescence. These analyses showed
      that the ASV IN protein possesses a functional nuclear localization signal that
      spans amino acids 206 to 235 and displays limited homology with known nuclear
      transport signals.

PMID- 8985430
TI  - Viral determinants of rotavirus pathogenicity in pigs: production of reassortants
      by asynchronous coinfection.
AB  - A porcine rotavirus (prv), variant 4F, isolated in tissue culture from the feces
      of a Chinese pig with diarrhea, was found to have become highly pathogenic when
      passaged in gnotobiotic piglets (J. C. Bridger, B. Burke, G. M. Beards, and U.
      Desselberger, J. Gen. Virol. 73:3011-3015, 1992). Comparison with the closely
      related pig-apathogenic variant prv 4S suggested the outer capsid protein VP4
      (encoded by RNA 4) of prv 4F as a determinant for pathogenicity (B. Burke, J. C.
      Bridger, and U. Desselberger, J. Gen. Virol. 75:2205-2212, 1994; B. Burke, J. C.
      Bridger, and U. Desselberger, Virology 202:754-759, 1994). In order to provide
      more direct evidence, the pathogenic prv 4F variant which grows and forms plaques
      poorly in tissue culture was reassorted with the well-tissue-culture-adapted, pig
      apathogenic bovine rotavirus (brv; UK Compton strain). After asynchronous
      coinfection of cell cultures (first prv 4F, followed by brv 6 to 12 h later),
      several reassortants were isolated containing RNA 4 of prv 4F either alone
      (isolate B-F4) or together with one or two other genes of 4F in the genetic
      background of brv. Backcrossing of the monoreassortant B-F4 with prv 4S yielded a
      monoreassortant, S-F4, which carries RNA 4 of the 4F variant in the genetic
      background of prv 4S. The in vitro growth characteristics of these reassortants
      were analyzed, and the roles of VP4 in plaque formation and growth kinetics in
      cell culture were confirmed. The monoreassortant S-F4 and the parental viruses
      prv 4F and prv 4S are currently being tested for pathogenicity in gnotobiotic
      piglets (J. C. Bridger, G. Tauscher, and U. Desselberger, unpublished data).

PMID- 8985432
TI  - Health care reform and quality of care.

PMID- 8985431
TI  - Human rights reflections in daily medical practice.

PMID- 8985433
TI  - Climate, health and medicine in a changing world.

PMID- 8985434
TI  - Cancer and TV towers: association but not causation.

PMID- 8985435
TI  - Cancer incidence and mortality and proximity to TV towers.
AB  - OBJECTIVE: To determine whether there is an increased cancer incidence and
      mortality in populations exposed to radiofrequency radiations from TV towers.
      DESIGN: An ecological study comparing cancer incidence and mortality, 1972-1990,
      in nine municipalities, three of which surround the TV towers and six of which
      are further away from the towers. (TV radiofrequency radiation decreases with the
      square of the distance from the source.) Cancer incidence and mortality data were
      obtained from the then Commonwealth Department of Human Services and Health. Data
      on frequency, power, and period of broadcasting for the three TV towers were
      obtained from the Commonwealth Department of Communications and the Arts. The
      calculated power density of the radiofrequency radiation in the exposed area
      ranged from 8.0 microW/cm2 near the towers to 0.2 microW/cm2 at a radius of 4km
      and 0.02 microW/cm2 at 12 km. SETTING: Northern Sydney, where three TV towers
      have been broadcasting since 1956. OUTCOME MEASURES: Rate ratios for leukaemia
      and brain tumour incidence and mortality, comparing the inner with the outer
      areas. RESULTS: For all ages, the rate ratio for total leukaemia incidence was
      1.24 (95% confidence interval [CI], 1.09-1.40). Among children, the rate ratio
      for leukaemia incidence was 1.58 (95% CI, 1.07-2.34) and for mortality it was
      2.32 (95% CI, 1.35-4.01). The rate ratio for childhood lymphatic leukaemia (the
      most common type) was 1.55 (95% CI, 1.00-2.41) for incidence and 2.74 (95% CI,
      1.42-5.27) for mortality. Brain cancer incidence and mortality were not
      increased. CONCLUSION: We found an association between increased childhood
      leukaemia incidence and mortality and proximity to TV towers.

PMID- 8985436
TI  - Serious injuries in jet skiers.
AB  - Personal motorised watercraft (often referred to as jet skis) are an enjoyable
      leisure activity on the nation's waterways. However, there have been several
      serious accidents, and licensing requirements are deficient. Inconsistent
      reporting of accidents has hindered investigations into the causes. We describe
      six recent cases and the factors that may have contributed to accidents, and
      suggest ways to reduce the hazards associated with the sport.

PMID- 8985437
TI  - Childhood drowning in New South Wales 1990-1995: a population-based study.
AB  - OBJECTIVE: To review the circumstances of children drowning in New South Wales
      (NSW), 1990-1995, and to analyse trends. DESIGN: The NSW Paediatric Trauma Death
      Review Data Unit received coronial notification of childhood drowning deaths. Age
      specific annual drowning rates per 100,000 population were calculated. SUBJECTS:
      Children aged 0-14 years who died of drowning. RESULTS: 132 children drowned
      (96[73%] aged 0-4 years). There was was an overall decrease in incidence of
      drowning, from 2.0 to 1.5 per 100,000 population, and a decline in domestic pool
      drownings (from a peak of 15 in 1992 to five in 1995), and in drownings in
      waterways (from nine to six over the six-year period). However, drownings in
      baths and dams did not decrease. In general, boys were at higher risk than girls.
      CONCLUSIONS: Analysis of the drowning incidents indicates that, despite the
      decreases documented, we should not be complacent, and preventive programs are
      still warranted. All pools and dams should have well maintained fences between
      the body of water and the house. All infants aged under three and all epileptic
      children should be supervised in the bath by an adult. Children should be taught
      to swim, warned of the dangers of rivers and surf, and adequately supervised.

PMID- 8985438
TI  - Outbreak of cryptosporidiosis linked to an indoor swimming pool.
AB  - OBJECTIVE: To determine the extent and source of a community outbreak of
      cryptosporidiosis. DESIGN: Questionnaire-based survey and matched case-control
      study. SETTING: Sutherland area in southern Sydney, September 1994 to January
      1995. PARTICIPANTS: 70 patients reported by pathology laboratories to have stool
      specimens positive for cryptosporidia, of whom 43 were surveyed; 35 were compared
      with age- and neighbourhood-matched controls. MAIN OUTCOME MEASURES: Demographic
      characteristics and potential risk factors in the two weeks before onset of
      illness. RESULTS: Laboratories reported 70 cases of cryptosporidiosis between
      September 1994 and January 1995. We found no association between illness and
      foods consumed or contact with people with diarrhoea or sick animals in the two
      weeks before onset. Seventeen of the case group (49%) reported swimming in a
      particular indoor swimming pool, compared with only seven controls (20%) (odds
      ratio, 3.7; P = 0.015). Cryptosporidial oocysts were detected in water from the
      swimming pool in January 1995. CONCLUSIONS: The outbreak of cryptosporidiosis was
      probably associated with ingestion of water from the indoor swimming pool,
      presumably contaminated by infected bathers. RECOMMENDATIONS: As it is difficult
      to eradicate cryptosporidia from swimming pools by either disinfection or
      filtration, we recommend that: People with recent diarrhoea should avoid public
      swimming pools; and Non-toilet-trained and faecally incontinent swimmers should
      be provided with alternative swimming facilities with separate water and
      filtration systems. To enable appropriate public health responses: Doctors and
      pathology laboratories should consider cryptosporidiosis in patients with
      diarrhoea lasting longer than three days; and Laboratory reporting of
      cryptosporidia to local health departments should be mandatory in all States and
      Territories.

PMID- 8985439
TI  - Digging in the desert.
AB  - Palaeopathology is the study of disease in antiquity. Doctor Christopher Browne
      has spent several years studying skeletal material recovered from an
      archaeological site in Jordan to gain insight into the evolution of rheumatic and
      bone diseases.

PMID- 8985440
TI  - Revealing secrets of a lost city. An archaeologist examines skeletal remains from
      the ruins of Pompeii.
AB  - Escape from the AD 79 volcano was possible for most inhabitants of the ancient
      city, even the elderly and infirm. Doctor Estelle Lazer challenges established
      views about those who perished.

PMID- 8985441
TI  - Medical travel: an opportunistic disease.

PMID- 8985442
TI  - HUGs: holidays for undergraduates.

PMID- 8985443
TI  - Hard times for homeless people.

PMID- 8985444
TI  - Children in homeless families in Melbourne: health status and use of health
      services.
AB  - OBJECTIVE: To determine the prevalence of health and behaviour problems in a
      sample of children in homeless families and of psychological problems in their
      parents, and to assess the use of health services by homeless families. DESIGN: A
      cross-sectional, questionnaire-based prevalence survey. SETTING: Supported
      accommodation provided by a welfare service in Melbourne between May 1994 and
      June 1995. SUBJECTS: 51 children from 31 families soon after housing crises.
      RESULTS: More than one-third of all children had total behaviour problems scores
      in the "deviant" range (i.e., requiring mental health referral). Intellectual
      disability/developmental delay, skin problems, vision problems, recurrent
      headache, and asthma or other breathing problems were more prevalent in these
      homeless children than in a large Australian normative population. Their mothers
      scored higher than a large normative sample on the mental health questionnaire,
      most markedly for "anxiety-insomnia", "severe depression" and total score. Cost
      of treatment and transport difficulties were seen as barriers to using health
      care services. RECOMMENDATIONS: Australian health-care practitioners should be
      aware of the health and health service access problems of children in homeless
      families, and work to minimise their physical, emotional, developmental and
      academic disadvantages. Psychological support services should be available for
      homeless families, particularly for mothers.

PMID- 8985445
TI  - Asylum seekers: general health status and problems with access to health care.
AB  - OBJECTIVE: To investigate the general health status of asylum seekers and their
      access to health services. DESIGN: Prospective questionnaire survey. SETTING: A
      community-based asylum seeker centre in Sydney from March to September 1994,
      before the Limited Health Care Assistance Scheme had taken effect. PARTICIPANTS:
      Forty of 57 eligible asylum seekers from 21 different countries attending English
      language classes. MAIN OUTCOME MEASURES: Results on the traumatic events section
      of the Harvard Trauma Questionnaire, a postmigratory problem checklist, the COOP
      Functional Health Assessment charts, the Duke-University of Northern Carolina
      Health Profile, and a structured interview to assess difficulties in accessing
      health care in Australia. RESULTS: More than 30 of the 40 participants reported
      exposure to past trauma. Asylum seekers were more impaired in their emotional
      health than a normative group of patients with minor (P < 0.001) and serious (P <
      0.001) medical illnesses, and more impaired in role functioning than those with
      minor medical illnesses (P < 0.001). Twenty or more reported symptoms of
      nervousness, headache, and/or depression; 28 reported having pain in the previous
      four weeks. Twenty-seven reported major difficulties in accessing dental
      services. The same number reported problems in obtaining general medical care;
      the most important reason cited was not having a Medicare card. CONCLUSIONS:
      Although a selective sample, the asylum seekers in our study appeared to be
      suffering substantial levels of emotional and somatic symptoms, yet, for most,
      access to health care was a major problem. The effectiveness of recent sequential
      changes to the provisions covering welfare and health care for asylum seekers
      needs to be closely monitored.

PMID- 8985446
TI  - Health care delivery system and major health issues in China.

PMID- 8985447
TI  - Health services in Indonesia.

PMID- 8985448
TI  - The Queensland Institute of Medical Research. Excellence from the interplay of
      medicine and science.
AB  - Funded largely through successfully competing for peer-reviewed grants, QIMR is
      moving rapidly into research based on the sophisticated technology of molecular
      biology and genetics. Yet the clinical objectives of research still motivate and
      inform the research effort.

PMID- 8985449
TI  - The Garvan Institute of Medical Research. Setting the agenda for medical research
      into the 21st century.

PMID- 8985450
TI  - Forty years at the pitface in the Walter and Eliza Hall Institute of Medical
      Research.
AB  - Donald Metcalf's contributions to the understanding of haemopoietic growth
      factors have led to the use of G-CSF and GM-CSF as valuable new therapies in
      medical oncology. We asked Professor Metcalf to reflect on his 40 years in
      medical research (most of it spent at the laboratory bench) and to give us his
      thoughts on the evolution of the Australian research effort.

PMID- 8985451
TI  - Australia's fourth Nobel laureate for medicine.

PMID- 8985452
TI  - Worldwide deaths and severe envenomation from jellyfish stings.

PMID- 8985453
TI  - Severe envenomation by the taipan (Oxyuranus scutellatus)
AB  - We describe cases of five patients with taipan envenomation which indicate that
      patients with paresis benefit from repeated doses of antivenom, even if given
      long after the bite, and that fresh frozen plasma should be given to correct
      coagulopathy that persists after reversal of neuromuscular blockade. We reiterate
      the importance of compression bandages.

PMID- 8985454
TI  - Foodborne disease: how to respond?

PMID- 8985455
TI  - Foodborne disease: emerging problems and solutions.
AB  - Foodborne disease is increasing in industrialised countries for complex reasons,
      including changes in the aetiological agents, the population at risk and food
      production and processing. It is unlikely ever to be eliminated, but the risk can
      be minimised. A preventive, rather than reactive, approach to ensuring food
      safety from "paddock to plate" is proposed for Australia, bringing it in line
      with many of its trading partners.

PMID- 8985456
TI  - Foodborne disease: current trends and future surveillance needs in Australia.
AB  - Review of 128 outbreaks of foodborne disease (affecting almost 6000 people, with
      six deaths) between 1980 and 1995 and available surveillance data showed that
      foodborne disease in Australia is similar to that in other industrialised
      countries. Campylobacter spp. and non-typhoidal Salmonella spp. were the most
      commonly reported pathogens. However, Australia, unlike the UK and US, lacks a
      comprehensive national surveillance system for foodborne diseases. This is
      essential to improve control of these diseases.

PMID- 8985457
TI  - An encounter with a Haitian refugee boat.

PMID- 8985458
TI  - The caesarean section.

PMID- 8985459
TI  - Did Leonardo da Vinci have a BCC?

PMID- 8985460
TI  - ACE-inhibitor cough in the Australian pink galah.

PMID- 8985461
TI  - A drug-free Olympics--a goal for spectators as well as athletes.

PMID- 8985462
TI  - "Christmas eye".

PMID- 8985463
TI  - Leather, oranges, dead pigs and needlestick injuries.

PMID- 8985464
TI  - Continuous measurement of tissue oxygen and carbon dioxide gas tensions in dog
      liver in ischemia/reperfusion.
AB  - An experiment was conducted to determine whether the oxygen and carbon dioxide
      gas tensions in liver tissue (PtO2 and PtCO2, respectively) reflect the state of
      microcirculation and/or metabolism in the ischemic liver. Subjects were divided
      into three groups: group 1, 30 min ischemia; group 2, 60 min ischemia; group 3,
      four times of intermittent 15 min ischemia after every 10 min of reperfusion.
      PtO2, PtCO2 and tissue blood flow (TBF) were measured by mass spectrometry,
      comparatively studied with the serum GOT level as an indicator of liver tissue
      damage. Furthermore, the time point at which the PtCO2 increase for 1 min
      initially became less than 1/2 of the maximum value was located on the transit
      curve of PtCO2, referred to as the critically anaerobic (CA) point, with which
      new indices of critically anaerobic score (CAS) and time (CAT) (see details in
      text) were developed. The profiles of PtO2 and PtCO2 during ischemia and
      reperfusion were clearly demonstrated, and the CA point was observed 12.7 +/- 2.9
      min after induction of ischemia. PtO2 was positively correlated with TBF and
      negatively with the serum GOT level. Furthermore, not only CAS but also CAT were
      significantly correlated with PtO2, TBF, and the serum GOT level. It was
      concluded that PtCO2 reflects the state of anaerobic tissue metabolism during
      ischemia and PtO2 reflects the magnitude of microcirculatory disturbance and
      tissue injury caused by ischemia/reperfusion. Therefore, continuous monitoring of
      not only PtO2 but also PtCO2 is beneficial for patients undergoing hepatic
      surgery with ischemia.

PMID- 8985465
TI  - Increased endothelial and epidermal thrombomodulin expression and plasma
      thrombomodulin level in progressive systemic sclerosis.
AB  - To clarify the relation between systemic and cutaneous vascular endothelial
      injury in progressive systemic sclerosis (PSS), we examined thrombomodulin (TM)
      expression in PSS skin lesions immuno-histopathologically and compared it with
      plasma soluble TM levels measured by specific enzyme-linked immunosorbent assay.
      The plasma soluble TM level in PSS patients was significantly higher than that of
      normal controls and was as high as the levels of SLE patients. In relation to
      disease activities, the plasma TM levels of sclerotic phase PSS patients were
      significantly higher than that of atrophic phase PSS patients. The plasma samples
      with anti-Scl-70 antibody showed a high TM level than samples with anti
      centromere antibody or anti-RNP antibody. Barnett's types or systemic
      corticosteroid treatment did not affect the TM level. Histopathologically, the
      dermal endothelial TM expression significantly increased in the sclerotic skin
      and moderately increased in the non-sclerotic skin of PSS compared with that of
      normal control skin. In addition, immunoreactive TM expression in the epidermis
      also increased in PSS. Disease activity-dependent elevation of plasma TM levels
      and immuno-histopathological expression of TM suggested generalized endothelial
      and epidermal cell involvement in PSS, and compensation in part by overproduction
      of TM by endothelial cells.

PMID- 8985466
TI  - Cathepsin B in the growth of colorectal cancer: suppressive effect of leupeptin
      on the growth of DMH-induced rat colon neoplasm.
AB  - Cathepsin B, a thiol protease, has been reported to be involved in cancer
      progression and metastasis. The suppressive effects of two kinds of protease
      inhibitors, leupeptin and dietary camostate (FOY-305), on tumorigenesis and
      progression in 1, 2-dimethylhydrazine (DMH)-induced rat colon neoplasm were
      examined in relation to tissue cathepsin B activity. Male Donryu rats were
      treated with leupeptin or FOY-305 during or after the administration of DMH.
      There were no significant differences in average tumor numbers among all DMH
      treated groups. However, the percentage of small tumors was significantly higher
      in the group in which leupeptin was supplied during DMH administration. This
      trend was not recognized in the FOY-305-treated groups. The ratio of cathepsin B
      activity in the tumors to that in the tumor-bearing tissue (T/Tb) was
      significantly increased with increasing tumor size (P = 0.009). The cathepsin B
      activity levels in the tumor-bearing mucosa in the groups which received
      leupeptin or FOY-305 following DMH treatment were both significantly lower than
      that in the group which received neither protease inhibitor (P = 0.046 and P =
      0.0067, respectively). The results obtained indicate that leupeptin may have
      suppressed tumor growth by lowering the tissue cathepsin B activity.

PMID- 8985467
TI  - Cathepsin B in the growth of colorectal cancer: increased activity of cathepsin B
      in human colorectal cancer.
AB  - Cathepsin B, a thiol protease, is involved in cancer metastasis. To clarify the
      role of cathepsin B in tumor progression in human colorectal cancer, the
      relationship between its activity, immunohistochemical staining, and clinical
      tumor progression was investigated. Cathepsin B activity in adenocarcinomas was
      significantly elevated compared with that in the tumor-bearing tissue.
      Furthermore, the tumor/tumor-bearing tissue (T/Tb) ratio of the activity was
      significantly higher than that of colorectal adenoma. Immunohistochemical studies
      demonstrated intense staining in the cancerous tissue. With respect to the
      clinical stage of tumors, the activity tended to be higher in tumors that had
      invaded the serosa or subserosa than in those that invaded the proper muscle. The
      results suggest that cathepsin B participates in the progression of human
      colorectal cancer, and its increased expression is a sensitive marker of the
      differentiation between colorectal adenoma and adenocarcinoma.

PMID- 8985468
TI  - Perineuronal sulfated proteoglycans, cell surface glycoproteins and dark neurons
      in the cingulate cortex of newborn and adult rats.
AB  - Many neurons in the adult rat cingulate cortex possess perineuronal sulfated
      proteoglycans detectable with cationic iron colloid and aldehyde fuchsin, or cell
      surface glycoproteins reactive to lectin Vicia villosa or soybean agglutinin. The
      perineuronal sulfated proteoglycans develop three to four weeks after birth. The
      cell surface glycoproteins develop at earlier stage or two to three weeks after
      birth. Dark or active neurons begin to appear three to four weeks after birth.
      These findings indicate that the brain matures after birth or during weaning
      period.

PMID- 8985469
TI  - Immortalization of cells from brains derived from a strain (MSM/MSfB6C3F1) of
      wild mouse.
AB  - Escape from cellular aging is the rate-limiting step of multistep carcinogenesis.
      While normal human cells invariably undergo cellular aging and almost never
      spontaneously immortalize, cells derived from rodents such as mice are relatively
      easily immortalized. In this experiment, we studied the immortalization patterns
      of cells obtained from brain tissues of an inbred strain (MSM/MSfB6C3F1) derived
      from wild mice. We established 12 cell strains derived from 12 mouse brains in
      order to investigate whether these cells show cellular aging in the same fashion
      as human cells or whether these cells are immortalized as easily as rodent cells
      reported previously. As a result, all cell strains were immortalized up to about
      200 days in culture. One strain immortalized very early, in the first 50 days,
      four strains immortalized in the last 200 days, and the other seven strains
      became immortal between 150 and 200 days in culture. All immortalized cell
      strains showed varying amounts of chromosome abnormalities, numerically and
      structurally, but no specific changes related to immortalization were detected.
      Before immortalization, three types of cells, glial-like, polygonal flat-thin,
      and fibroblast-like cells, were observed in culture, but after immortalization
      most of the cultures became fibroblastic. From these results, we concluded that
      fibroblast-like cells derived from brains of these mice immortalized in like
      fashion to fibroblasts of other inbred mice.

PMID- 8985470
TI  - Relation between the instrumental activities of daily living and physical fitness
      tests in elderly women.
AB  - A cross-sectional study was conducted to quantitatively evaluate the relationship
      between the instrumental activities of daily living (IADL) and various physical
      fitness tests in elderly women living at home. The study focused on the total
      population of those women aged 65 years and over living in Y Town, Hyogo
      Prefecture, Japan, who visited a nursing home for day services. A total of 128
      subjects were divided into two groups: dependent in IADL group (n = 49) and
      independent in IADL group (n = 79). The magnitude of the relation was evaluated
      by the odds ratio (OR). The following tests showed a significant decrease in
      IADL: knee-raising test [age-adjusted OR = 4.23, 95% confidence interval (CI)
      1.81-9.87], height (age-adjusted OR = 4.09, 95% CI 1.75-9.56), grip strength (age
      adjusted OR = 3.68, 95% CI 1.57-8.60), sit-and-reach test (age-adjusted OR =
      2.76, 95% CI 1.20-6.34), and standing on one leg with closed eyes (age-adjusted
      OR = 2.56, 95% CI 1.09-5.97). Multivariate analysis using Hayashi's
      quantification method I indicated that knee-raising was the test most highly
      correlated with decreased IADL. These results suggest that measurement of knee
      raising ability, muscle strength of the lower extremities and flexibility of hip
      joint could be the most useful factors to assess the level of instrumental self
      support ability.

PMID- 8985471
TI  - The role of cognition in the risk--benefit and safety analysis of antipsychotic
      medication.
AB  - Conventional neuroleptics can further reduce cognitive function, which is already
      impaired in most patients with schizophrenia. Although some areas of cognition
      may remain relatively well preserved in schizophrenia, it has been suggested that
      the origins of a neurocognitive decline in schizophrenia may be related to a
      reduction in dopamine activity in the prefrontal cortex. If this is the case,
      dopamine D2 blockade would be expected to impair some aspects of neurocognitive
      function further. The level of neurocognitive function in schizophrenia is
      related to vocational and social ability, and the course of cognitive decline
      appears to be consistent with a static encephalopathy, rather than progressive
      dementia. Intensive cognitive retraining in patients with schizophrenia may
      improve, but not normalize, some aspects of cognitive performance. Most cognitive
      deficits remain stable, even when improvements in symptoms are obtained with
      antipsychotic treatment. Drugs such as risperidone, one of the newer serotonin
      dopamine antagonists (SDAs), have a better effect on cognitive function than
      conventional antidopaminergic neuroleptics, and are therefore more likely to
      enable the patient to benefit from cognitive and other forms of training.
      Anticholinergic drugs used to treat EPS, or drugs with anticholinergic activity,
      also impair cognitive function. Consequently, because the need to use
      anticholinergic drugs is less with the SDA antipsychotics, the cognitive function
      of patients treated with drugs such as risperidone is likely to be better than it
      would be if they took a conventional neuroleptic.

PMID- 8985472
TI  - Spontaneous and drug-induced movement disorders in schizophrenia.
AB  - The extrapyramidal side-effects (EPS) of conventional neuroleptics are widely
      recognized. However, a substantial number of drug-naive patients exhibit movement
      disorders which could be mistaken for EPS if drug therapy were started without a
      careful baseline assessment. Patients' experience of EPS during their first
      exposure to antipsychotic medication can have lasting effects on their attitudes
      to medication and compliance. Unmedicated, approximately 60% of patients will
      relapse in the first year after resolution of an acute psychotic episode, whereas
      prophylactic medication can reduce the relapse rate to less than 20%. The
      conventional neuroleptics produce antipsychotic effects at doses which differ
      little from those that induce EPS, and although anticholinergic medication helps
      to reduce the severity of EPS, it also causes side-effects, e.g. constipation,
      blurred vision, retention of urine, dry mouth and disturbances of sexual
      function. More importantly, anticholinergic drugs may worsen the psychosis and
      impair memory. Low or intermittent dose strategies with conventional neuroleptics
      may give patients relief from EPS, but they increase the relapse risk, and may
      also increase the risk of tardive dyskinesia. The serotonin-dopamine antagonist
      (SDA) antipsychotics, such as risperidone, produce both significant antipsychotic
      effects at doses which are lower than those that cause EPS, and also a lower
      level of EPS compared with conventional drugs. Clinical trials have shown that
      risperidone is effective in first-episode schizophrenia. In these trials the same
      doses were used as in chronic patients. However, clinical experience in Canada
      since the drug became generally available in 1993 suggests that first-episode
      patients require lower doses of risperidone than chronically ill patients who
      have had several acute psychotic episodes. More than 3 years of use has made it
      clear that risperidone should be seriously considered in first-episode patients,
      as it offers an opportunity to treat psychosis with minimal EPS. This in turn
      should lead to better compliance and a lower long-term relapse rate.

PMID- 8985473
TI  - Minimizing the non-extrapyramidal side-effects of antipsychotics.
AB  - Standard neuroleptic medications have been augmented by the introduction of
      risperidone and clozapine into clinical practice. A great deal of attention has
      also been focused on efficacy and the lower propensity to extrapyramidal side
      effects associated with the new agents. However, antipsychotic medication, both
      old and new, can cause a range of other adverse effects, some of which are
      serious, and many of which have the potential greatly to diminish the quality of
      life of patients who need to take medication in the long term. Of particular
      significance are postural hypotension, cardiotoxicity, peripheral and central
      anticholinergic effects, sedation, weight gain, and endocrine and haematological
      effects. Various antipsychotic compounds differ substantially with regard to
      propensity to adverse effects. Side-effects can be minimized by optimization of
      clinical strategies, including choice of appropriate drug, slow titration and
      dosage reduction. It is also vital to explain carefully to both patients and
      carers the nature of the side-effects which can be anticipated. The choice of
      antipsychotic is often determined by evaluation of the potential impact of the
      various adverse effects on a particular patient. New drugs, such as risperidone,
      are well tolerated, with fewer side-effects, and should now be considered as a
      first-line option.

PMID- 8985475
TI  - Neutrophils and allergy.

PMID- 8985474
TI  - Antigen receptor signalling.

PMID- 8985476
TI  - Eosinophils and allergy.

PMID- 8985477
TI  - Formation of lipids, peptides and cytokines.

PMID- 8985478
TI  - Granular proteins of eosinophils.

PMID- 8985480
TI  - The Christmas present.

PMID- 8985479
TI  - Eosinophil receptors.

PMID- 8985481
TI  - Chromosome 22q11.2 microdeletions in velocardiofacial syndrome patients with
      widely variable manifestations.
AB  - Velocardiofacial syndrome (VCFS) and the DiGeorge sequence (DGS) are caused by
      22q11.2 deletions. Fluorescence in situ hybridization (FISH) using the DiGeorge
      chromosome region (DGCR) probe (Oncor) was used to detect 31 deletions in 100
      patients with possible VCFS. Retrospective FISH analysis of archived slides from
      14 patients originally studied only by high-resolution G banding detected 6
      patients with a DGCR deletion, and only 2 of these 6 had a microscopically
      visible chromosome deletion. The 4 familial deletions found exhibited a wide
      range of clinical presentations within each family. Comparison of clinical
      characteristics of patients with and without the DGCR deletion determined
      findings predictive of the deletion: abundant or unruly scalp hair; narrow
      palpebral fissures; a laterally "built-up" nose; velopharyngeal inadequacy;
      thymic hypoplasia; and congenital heart defects, specifically tetralogy of
      Fallot, ventriculoseptal defect, and interrupted aortic arch.

PMID- 8985482
TI  - Total anonychia congenita and microcephaly with normal intelligence: a new
      autosomal-recessive syndrome?
AB  - We report on 3 sibs (2 boys and a girl) with a previously apparently unrecognized
      combination of anonychia congenita and microcephaly with normal intelligence. The
      shape of the head is normal. Other anomalies include clinodactyly of the fifth
      fingers and bilateral single transverse palmar creases. Skeletal survey was
      normal in the 2 older children. These children and their first-cousin Iranian
      parents have widely spaced teeth. The children's first cousin also has total
      anonychia congenita and apparently small head. We review anonychia congenita, and
      conclude that the presently reported family with a "new autosomal-recessive
      disorder" provides further evidence of the heterogeneity of this condition.

PMID- 8985483
TI  - Greig cephalopolysyndactyly syndrome with dysgenesis of the corpus callosum in a
      Bedouin family.
AB  - We report on the first known Bedouin family with Greig cephalopolysyndactyly
      syndrome (MIM 175700). The index patient and his father shared pre- and postaxial
      polysyndactyly, mild mental retardation, and corpus callosum dysgenesis. Their
      phenotypic findings were compared with reported cases of both Greig
      cephalopolysyndactyly (GCPS) and acrocallosal syndromes. This family represents
      the second report of the rare occurrence of dysgenesis of the corpus callosum in
      GCPS.

PMID- 8985484
TI  - Autosomal recessive severe dwarfism in a Sicilian girl: a new form of
      osteodysplastic primordial dwarfism?
AB  - A new type of osteodysplastic primordial dwarfism is delineated in a 5-year-old
      female child with severe growth retardation of prenatal onset, gross skeletal
      changes, a non-Seckel facial phenotype, and presumed autosomal recessive
      inheritance.

PMID- 8985485
TI  - Clinical and roentgenographic findings in a patient with primordial microcephalic
      dwarfism type Caroline Crachami.
AB  - We describe a patient with primordial microcephalic dwarfism with severe
      intrauterine growth retardation and severe and progressive postnatal deficit in
      length, weight and head circumference. The patient was extroverted and sociable
      but mildly mentally retarded. He had marked delay of bone maturation and an
      enlargement of the sella turcica. This child and two previously reported patients
      [Boscherini et al., Eur J Pediatr 137:237-242, 1981] have many characteristics in
      common with Caroline Crachami, the famous "Sicilian dwarf". We think that these
      patients belong to a separate category of microcephalic primordial dwarfism.

PMID- 8985486
TI  - Distichiasis-lymphedema syndrome: tetralogy of Fallot, chylothorax, and neonatal
      death.
AB  - We describe a newborn female with a severe presentation of distichiasis
      lymphedema syndrome (McKusick 15340). She was initially evaluated because of a
      phenotype suggestive of Ullrich-Turner or Noonan syndrome (low posterior
      hairline, cupped ears, severe pterygium colli, heart murmur, and pectus
      excavatum). Distichiasis was noted at age 6 weeks. Subsequent to surgery for
      tetralogy of Fallot, patent ductus arteriosus, and branch pulmonic stenosis, she
      developed persistent chylothorax and sepsis. She died at 3 months. Family history
      indicated segregation of distichiasis-lymphedema syndrome. She was the sixth
      member in her family to have this disorder and was the most severely affected.

PMID- 8985487
TI  - Familial ring (19) chromosome mosaicism: case report and review.
AB  - Ring (19) chromosomal mosaicism has been identified in a 14-month-old girl
      referred for cytogenetic evaluation due to microcephaly and developmental delay
      with autistic-like mannerisms. An analysis of her peripheral blood lymphocytes
      showed a 46,XX,r(19) cell line in 119/121 of cells examined. Of the two remaining
      cells, one had a normal female chromosome complement and the other showed loss of
      one of the chromosome 19 homologs. Further analysis by fluorescence in situ
      hybridization using an all human telomere probe showed the presence of a single
      hybridization signal on the r(19) chromosome. Subsequent cytogenetic
      characterization of cells derived from the patient's phenotypically normal mother
      also demonstrated the presence of a ring 19 chromosome in 4/100 cells. The
      remaining cells had a normal female chromosome complement. These findings
      represent the first reported case of familial ring 19 mosaicism. The cytogenetic
      and clinical findings in these two individuals are discussed in relation to six
      previously reported cases of de novo ring chromosome 19 mosaicism.

PMID- 8985488
TI  - Molecular detection of new mutations, resolution of ambiguous results and complex
      genetic counseling issues in Huntington disease.
AB  - Huntington disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by expansion of a variable length (CAG)n repeat in the 5' coding region of
      a novel gene on chromosome 4p16.3. We provide comprehensive molecular analysis of
      a sporadic case of HD in which a paternally derived normal length allele expanded
      to an affected length allele. Linkage analysis and paternity testing confirm the
      paternal origin of the expansion and demonstrate that unequal crossing over
      during meiosis is an unlikely mechanism for de novo expansion in HD. This case
      identifies a complex genetic counseling issue for the families of sporadic cases
      since calculations of recurrence risk are not possible at this time. In addition,
      we describe utilization of a combination of polymerase chain reaction (PCR) based
      assays for examination of both the CAG repeat and an adjacent variable length CCG
      repeat in the huntingtin gene. The combination of these assays can increase the
      accuracy of molecular diagnosis for HD and may clarify any ambiguous results
      obtained during molecular testing of HD families.

PMID- 8985489
TI  - Reduced stereoacuity in Williams syndrome.
AB  - Strabismus is a frequently recognized manifestation of Williams syndrome
      [Greenberg and Lewis, 1988: Ophthalmology 95:1608-1612; Kapp et al., 1995: Am J
      Ophthalmol 119:355-360]. We recently evaluated the ophthalmologic function of 12
      patients with Williams syndrome (WS), with an emphasis on binocularity. Four of
      12 patients (33%) had measurable strabismus. Of the 8 remaining patients,
      examination of binocular function was possible in 6, all of whom demonstrated
      reduced stereoacuity. We speculate that subnormal binocular vision and the poor
      visuospatial performance observed in patients with WS may be related to abnormal
      brain morphogenesis in the region of the occipitoparietal cortex.

PMID- 8985491
TI  - The floating harbor syndrome with cardiac septal defect.
AB  - The Floating Harbor syndrome of short stature, very delayed bone age, expressive
      language delay, and characteristic facial changes has not been associated with
      cardiac anomalies, except for one patient with pulmonic stenosis. We report on a
      10-year-old boy with the syndrome and tetralogy of Fallot with atrial septal
      defect.

PMID- 8985490
TI  - Clinicopathologic findings in congenital aneurysms of the great vessels.
AB  - We describe the clinical, histopathologic, and angiographic findings in four
      children with congenital abnormalities of the great vessels of unknown cause,
      comprising either single or multiple arterial aneurysms, aortic/arterial
      dilatation, vessel tortuosity, or combinations of these abnormalities. Two
      children had early and severe respiratory distress due to aneurysmal compression
      of the trachea. All children had diffuse dilatation of several arteries, and two
      children also had tortuosity of multiple arteries. Progression of these
      abnormalities was clearly evident in one child, in whom diffuse vessel
      irregularity and tortuosity affected intra-abdominal, and intra and extra-cranial
      arteries. One child died at 5 years, while the other three have undergone
      successful surgical repair in the first 3 months of life and are now well,
      between age 2.5 and 7 years. The phenotype of each child appears unique but all
      have in common the rare finding of aneurysms of the aorta and main pulmonary
      artery. Congenital aortic aneurysms did not occur as an isolated finding in any
      of these children.

PMID- 8985492
TI  - Multigeneration maternal transmission in Italian families with neural tube
      defects.
AB  - Periconceptional vitamin supplementation with folate prevents about three
      quarters of expected cases of neural tube defects (NTDs) in clinical trials.
      However, vitamin action may be regulated at the level of the gene, and individual
      susceptibility to environmental agents, including dietary components, also may be
      under genetic control. We investigated the presence of familial factors in a
      retrospective case control study of neural tube defects in Genoa, Italy. Cases
      included all patients treated at a single pediatric neurosurgical service.
      Controls matched on age and sex came from the same hospital. We found strong
      evidence for the contribution of genetic factors in this study. There was an
      excess risk of 14 for the occurrence of NTDs in first-degree relatives compared
      to controls (P < .0005). There was no difference in sex ratio in any group of
      relatives, but maternal grandparents of children with a high spinal lesion had
      14% fewer off-spring than paternal grandparents (P < .005), possibly because of
      excess miscarriages. Our study is the first to show complex patterns of
      inheritance in spina bifida families affecting three generation in one clinical
      subgroup and preferentially on the mother's side. These results support a role
      for genomic imprinting and highlight the value of multidisciplinary epidemiologic
      and clinical studies that include multiple generations. New studies incorporating
      dietary and genetic approaches will help clarify and extend these findings.

PMID- 8985493
TI  - Clinical and biochemical heterogeneity in females of a large pedigree with
      ornithine transcarbamylase deficiency due to the R141Q mutation.
AB  - A large family with ornithine transcarbamylase deficiency due to mutation R141Q
      was ascertained through a propositus who presented with acute neonatal
      hyperammonemic coma. Of 13 females at risk, 11 were evaluated clinically and had
      laboratory studies performed. Seven were found to be heterozygous for the
      mutation. Of these seven, five had chronic clinical symptoms and two were
      asymptomatic. None of the heterozygotes had elevated plasma ammonia on random
      testing. Of the five symptomatic females, three had markedly elevated plasma
      glutamine levels on random testing, while two had levels in the upper range of
      normal. Plasma citrulline and arginine levels were somewhat lower in the
      symptomatic individuals but still within the normal range. Five heterozygotes who
      were tested had either spontaneous orotic aciduria or elevated orotic acid
      following ingestion of allopurinol, whereas one unaffected female and one
      unaffected male had normal allopurinol tests. A higher than expected proportion
      of female heterozygous for the R141Q mutation were clinically and biochemically
      symptomatic but remained undiagnosed for many years. Plasma glutamine
      determination and allopurinol testing should be performed in females who present
      with a combination of relatively non-specific symptoms detailed in this report.

PMID- 8985494
TI  - 55-base pair deletion in certain patients with Gaucher disease complicates
      screening for common Gaucher alleles.
AB  - Mutations in the glucocerebrosidase gene which result in Gaucher disease can
      originate from the highly homologous glucocerebrosidase pseudogene. A 55-bp
      deletion in exon 9, which corresponds to a 55-bp segment absent from the
      pseudogene, has been identified in patients with Gaucher disease. We have
      developed a simple polymerase chain reaction (PCR)-based method to detect this 55
      bp deletion, and have found this mutation in 3 of 75 DNA samples (4%) collected
      from patients with Gaucher disease. Commonly used PCR-based screening methods for
      specific Gaucher mutations frequently make use of primers either within or
      surrounding the 55-bp gap to selectively distinguish the glucocerebrosidase gene
      from the pseudogene. However, if the 55-bp deletion in exon 9 occurs, primers
      will either fail to produce an amplification product or will produce a shortened
      product which will be falsely attributed to the pseudogene. This could lead to
      inaccurate genotyping and genetic counseling for some Gaucher patients and their
      families. We therefore recommended that laboratories using PCR-based screening
      techniques involving primers in this region initially determine whether this 55
      bp sequence is present.

PMID- 8985496
TI  - Genetic disorders in portraits.
AB  - Many artists have depicted genetic disorders in portrait paintings. In some
      instances such disorders can be identified in self-portraits, most notably the
      tetralogy of Fallot in the Dutch painter Dick Ket, or in portraits of the famous,
      such as the Habsburg jaw in the Emperor Charles V. But it is in other portraits
      that most examples can be found, such as the different types of dwarfism depicted
      by Velazquez. A table listing over 70 examples is provided.

PMID- 8985495
TI  - Descriptive epidemiology of holoprosencephaly and arhinencephaly in metropolitan
      Atlanta, 1968-1992.
AB  - We report the descriptive epidemiology of holoprosencephaly and arhinencephaly
      using data from the Metropolitan Atlanta Congenital Defects Program, a population
      based birth defects surveillance system with multiple sources of ascertainment.
      From 1968-1992, we ascertained 63 cases of holoprosencephaly and arhinencephaly
      from approximately 734,000 births, for a birth prevalence of 0.86 per 10,000.
      Thirteen case infants with holoprosencephaly and four case infants with
      arhinencephaly were categorized as having syndromes. Of the case infants with non
      syndromic holoprosencephaly, 55% had malformations not attributable to the
      underlying brain defect. The rate of holoprosencephaly and arhinencephaly
      increased from 0.58 per 10,000 during 1968-1972 to 1.2 per 10,000 during 1988
      1992 (P for trend = 0.016). Rates were higher for females than for males (risk
      ratio = 1.45, 95% C.I. 0.88-2.41) and higher for nonwhites than for whites (risk
      ratio = 1.74, 95% C.I. 1.06-2.86). There was a U-shaped distribution of risk
      associated with maternal age with a slightly increased risk for younger women
      (risk ratio for maternal age < 20 years, compared with age 25-29 years = 1.68,
      95% C.I. 0.77-3.62) and older women (risk ratio for maternal age > 34 years,
      compared with age 25-29 years = 2.30, 95% C.I. 0.93-5.7), but this was not
      statistically significant. The increased risk in the older age group could be
      largely explained by the presence of cases with autosomal trisomies. Neonatal
      mortality was higher for infants with malformations that were not attributable to
      the underlying brain defect and for infants with syndromes than for infants with
      isolated holoprosencephaly. This analysis is the first population-based study
      with long-term data on this rare defect. Further epidemiologic studies will be
      necessary to assess the risk factors for holo-prosencephaly and arhinencephaly.

PMID- 8985497
TI  - Sperm acrosome defects in a patient with Aarskog-Scott syndrome.
AB  - We describe a man with Aarskog-Scott syndrome. Infertility and recurrent
      spontaneous abortions were the primary complaints. The andrological examination
      demonstrated an unusual scrotal anomaly and a defect of sperm acrosomes.

PMID- 8985498
TI  - Diagnostic problems in a case with mucometrocolpos, polydactyly, congenital heart
      disease, and skeletal dysplasia.
AB  - Mucometrocolpos is the distention of the uterus and vagina caused by obstruction
      to the drainage of genital secretions. Although most cases of mucometrocolpos are
      sporadic, it may be part of an autosomal recessive condition, known as McKusick
      Kaufman syndrome (MKS), including postaxial polydactyly and congenital heart
      disease as main findings. The diagnosis may be difficult when the presence of
      additional findings creates an overlap with other syndromes. We report on a
      female infant with mucometrocolpos, postaxial polydactyly, congenital heart
      disease, short limbs, short ribs, and chest constriction. The clinicopathological
      findings are described and discussed in the context of the phenotypic spectrums
      of MKS and mucometrocolpos concomitant with Ellis van Creveld syndrome.

PMID- 8985499
TI  - Exclusion of allelism of Noonan syndrome and neurofibromatosis-type 1 in a large
      family with Noonan syndrome-neurofibromatosis association.
AB  - A large four-generation family with Noonan syndrome (NS) and neurofibromatosis
      type 1 (NF1) was studied for clinical association between the two diseases and
      for linkage analysis with polymorphic DNA markers of the NF1 region in 17q11.2.
      Nonrandom segregation between NS and NF1 phenotypes was observed.
      Neurofibromatosis was tightly linked to NF1 markers, whereas Noonan syndrome was
      found not be allelic to NF1. These results suggest that two mutations at two
      independent but closely linked loci are the cause of neurofibromatosis-Noonan
      syndrome (NF-NS) association in this family.

PMID- 8985500
TI  - Increased rate of routine second newborn screen in Washington state.

PMID- 8985501
TI  - Natural family planning and Down syndrome--matching and confounding in a case
      control study.

PMID- 8985502
TI  - Down syndrome and natural family planning.

PMID- 8985503
TI  - Medulloblastoma in patient with Rubinstein-Taybi syndrome.

PMID- 8985504
TI  - Inheritance of Niikawa-Kuroki (Kabuki makeup) syndrome.

PMID- 8985505
TI  - Monoclonal antibodies reacting against capacitated but not with freshly
      ejaculated boar spermatozoa.
AB  - PROBLEM: The involvement of individual sperm proteins in differentiation of
      antigenically specific and functionally defined regions on sperm membrane has not
      yet been completely elucidated. METHOD: BALB/c mice were immunized with live
      capacitated boar spermatozoa and used for production of monoclonal antibodies
      (MAbs). ELISA, IIF, SDS-PAGE, IVF, and cytologic methods were used for selection
      and biological characterization of MAbs as well as for identification of
      corresponding antigens. RESULTS: MAb1F10, MAb2E2, and MAb4B12 react with antigens
      in the acrosome portion of live capacitated spermatozoa, MAb 1F10 reacted with
      human sperm cells along with those from bull, ram, mouse, dog, whereas MAb2E2-
      with mouse's spermatozoa and MAB4B12-with bull's, mouse's, and dog's spermatozoa.
      Some glycolytic enzymes seemed to reduce mildly the reactions of the MAbs with
      enzyme treated sperm cells; proteolytic enzymes eliminated the binding of MAbs to
      the sperm acrosome. These MAbs have no sperm agglutinating and/or sperm
      immobilizing activities and reduced the number of spermatozoa binding to zona
      pellucida. CONCLUSIONS: MAb1F10, MAb2E2, and MAb4B12 seemed to recognize membrane
      associated antigens with potential role in the initial stages of fertilization,
      specific for capacitated but not for freshly ejaculated spermatozoa.

PMID- 8985506
TI  - Sperm, nuclear, phospholipid, and red blood cell antibodies and isotype RF in
      infertile couples and patients with autoimmune rheumatic diseases.
AB  - PROBLEM: To determine if measuring of nonorgan-specific autoantibodies is useful
      for better understanding and management of unexplained infertility. METHODS: Sera
      were obtained from 70 infertile couples, 57 rheumatic patients, and 76 fertile
      donors. Sperm antibodies (SA) were detected by the tests of Kibrick and Friberg,
      anti-histones, anti-cardiolipin antibodies, and RF isotypes by ELISA, antinuclear
      antibodies by indirect immunofluorescence, and anti-red blood cell antibodies by
      Capture-R. RESULTS: Multiple autoimmune reactivity (both partners positive and/or
      more than one type of autoantibody involved), higher than naturally occurring in
      fertile individuals, was found in 55% of the idiopathically infertile couples.
      IgA-RF was the dominant autoimmune marker. SA revealed similar rates in patients
      with rheumatic diseases and in infertiles with or without other autoantibodies.
      CONCLUSION: Although no single autoimmunity marker could predict occurrence of
      SA, the coincidence of enhanced polyclonal autoimmunity in both partners of
      infertile couples might potentiate their negative effect on reproduction.

PMID- 8985507
TI  - Identification of human sperm antigen recognized by serum of an immunoinfertile
      woman: a candidate for immunocontraception.
AB  - PROBLEM: It has been well documented that antisperm antibodies can be causative
      factors of infertility. In this study we have identified an antigen on human
      sperm surface using serum of an immunoinfertile woman; it is thus a candidate for
      immunocontraception. METHOD: Thirty-three women of reproductive age who were
      infertile were screened for presence of antisperm antibodies by indirect
      immunofluorescence and agglutination assay. The serum of one such woman, SU-4,
      reacted with her husband's as well as normal donor sperm and recognized a band of
      apparent molecular weight of 71-kDa on Western blot. Anti-71-kDa antiserum was
      raised in rabbit by eluting 71-kDa protein and was characterized by agglutination
      test, immunofluorescence assay, transmission electron microscopy, flow cytometry,
      and sperm-egg interaction in mouse system. RESULTS: Interestingly, sera raised in
      rabbit against 71-kDa antigen, was identified by immunoinfertile serum of SU-4,
      revealed similar results of localization of human acrosome. Anti-71-kDa
      antibodies showed cross-reactivity with other species of sperm, demonstrated
      inhibition of sperm attachment to oocytes in an in vitro mouse system, and
      revealed surface binding of human live sperm by flow cytometry. Transmission
      electron microscopy documented the presence of 71-kDa antigen in the acrosomal
      compartment. CONCLUSION: This study has put in evidence an antigen of apparent
      molecular weight of 71-kDa in all donor sperm tested in this study. The presence
      of this antigen on the sperm of several species will enable us to determine the
      efficacy of this antigen in controlling fertility in vivo in both rodents and
      primates. This antigen may be a candidate for immunocontraception.

PMID- 8985508
TI  - Is irregular regression of corpora lutea in climacteric women caused by age
      induced alterations in the "tissue control system"?
AB  - PROBLEM: We have recently observed that the regression of corpora lutea (CL) in
      women during the reproductive period of life is accompanied by a diminution of
      Thy-1 differentiation protein release from vascular pericytes and an accumulation
      of T lymphocytes and activated macrophages among both degenerating granulosa
      lutein cells (GLC) and theca lutein cells. These data suggest that the immune
      system and other stromal factors, representing components of the "tissue control
      system," may play a role in regression of the CL. We investigated degenerating CL
      from climacteric women to address the possibility that the decline of immune
      functions with advancing age may result in incomplete regression of luteal
      tissue. This could contribute to the altered hormonal profiles and abnormal
      uterine bleeding that frequently occur during the climacteric. METHOD:
      Immunoperoxidase staining and image analysis were used to localize Thy-1
      differentiation protein of vascular pericytes, cytokeratin staining of GLC,
      neural cell adhesion molecule expression by theca lutein cells, CD15 of
      neutrophils, CD4, CD14, CD68, and leukocyte common antigens of macrophages, and
      CD3 and CD8 determinants of T lymphocytes. We also investigated the expression of
      luteinizing hormone receptor (LH receptor) and mitogen activated protein kinases
      (MAP kinases) in luteal cells. Samples of regressing luteal tissue were obtained
      during the follicular phase from perimenopausal women (age 45-50) who exhibited
      prolonged or irregular cycles. For comparison, luteal tissues from women with
      regular cycles (age 29-45) and CL of pregnancy were also investigated. RESULTS:
      Corpora lutea of the climacteric women exhibited irregular regression of luteal
      tissue characterized by a lack of cytoplasmic vacuolization and nuclear pyknosis
      in GLC, and by a persistence of theca lutein cells exhibiting hyperplasia and
      adjacent theca externa layers. This was accompanied by a continuing release of
      Thy-1 differentiation protein from vascular pericytes. Persisting GLC lacked
      surface expression of macrophage markers (CD4, CD14, CD68 and leukocyte common
      antigen) as well as nuclear granules exhibiting CD15 of neutrophils, detected in
      regularly regressing GLC. In addition, such persisting GLC showed weak or no LH
      receptor expression, and retained the expression of cytokeratin. They also
      exhibited enhanced staining for MAP kinases. Strong cytoplasmic MAP kinase
      expression with occasional nuclear translocation was also detected in persisting
      theca lutein cells, indicating high metabolic activity of these cells. T
      lymphocytes, although occasionally present in luteal stroma within luteal
      convolutions, did not invade among persisting GLC and were virtually absent from
      layers of theca externa and theca lutein cells. CONCLUSIONS: These data indicate
      that the regressing CL in climacteric women may exhibit persistence of luteal
      cells, perhaps because of age-induced alterations of the immune system and other
      local stromal homeostatic mechanisms involved in the elimination of luteal cells.
      Persisting GLC and/or theca lutein cells may exhibit abnormal hormonal secretion
      that contributes to the alteration of target tissues, such as the endometrium,
      resulting in abnormal uterine bleeding, hyperplasia, and neoplasia.

PMID- 8985509
TI  - Lymphocyte subsets in the endometrium of patients with endometriosis throughout
      the menstrual cycle.
AB  - PROBLEM: Comparison and characterisation of different lymphocyte subsets in the
      endometrium of endometriosis patients and in healthy women on every day of the
      menstrual cycle with special emphasis on the CD4:CD8 ratio in the endometrium.
      METHOD: Immunohistochemical staining of 253 endometrial biopsies of infertile
      women with and without endometriosis with Anti-Leu4 (CD3), Anti-Leu3a (CD4), Anti
      Leu2a (CD8), Anti-Leu7 and Anti-Human-B-cell (CD22) using the immune peroxidase
      reaction. Identification and counting of positive lymphocyte were performed on
      cryostat sections. RESULTS: Endometrial lymphocyte subsets show equal quantity
      and distribution in endometriosis patients and in the control group. After a peak
      in the early proliferative phase the absolute number of T lymphocytes decreases
      while a predominance of T-suppressor/cytotoxic T lymphocytes (CD8) compared to T
      helper/inducer lymphocytes (CD4) occurs towards the end of the menstrual cycle.
      CONCLUSION: Endometrium as the potential parent epithelia of endometriosis
      lesions seems not to be altered in its lymphatic cell content compared to healthy
      women. Furthermore, endometrium is clearly characterised as part of the mucosa
      associated lymphatic tissue (MALT). T lymphocytes show specific quantitative
      changes due to different phases of the menstrual cycle.

PMID- 8985510
TI  - Altered expression of human leukocyte antigen G (HLA-G) on extravillous
      trophoblasts in preeclampsia: immunohistological demonstration with anti-HLA-G
      specific antibody "87G" and anti-cytokeratin antibody "CAM5.2".
AB  - PROBLEM: Human leukocyte antigen-G (HLA-G) is suggested to be at play in the
      materno-fetal immune relationship during pregnancy. In the light of current
      concept that disruption of the materno-fetal immune relationship could account
      for several complications of pregnancy, including preeclampsia, we asked whether
      the expression of HLA-G protein on the trophoblasts is altered in preeclampsia.
      METHOD: The presence of HLA-G protein in the extravillous trophoblasts in
      placenta obtained from five preeclamptic patients and seven uncomplicated
      pregnant women was determined by means of an immunohistochemical technique.
      RESULTS: All of the extravillous trophoblasts, which were stained for
      cytokeratin, were stained for HLA-G protein in every woman with an uncomplicated
      pregnancy. In contrast, clusters of extravillous trophoblasts were insularly
      devoid of the staining for HLA-G in all the preeclamptic patients. CONCLUSION:
      The attenuated expression of HLA-G protein on the extravillous trophoblasts could
      be at play in the pathophysiology of preeclampsia.

PMID- 8985511
TI  - The enigma of local recurrence. The Society of Surgical Oncology.
AB  - Local recurrence has long been seen as a technical surgical failure to be avoided
      at all costs. This paper reviews the significance of local recurrence for the
      patient in terms of survival, using data derived from the study of extremity soft
      tissue sarcoma.

PMID- 8985512
TI  - Metastasis of primary melanoma to two separate lymph node basins: prognostic
      significance.
AB  - BACKGROUND AND METHODS: Depending on the location of the primary lesion, melanoma
      patients may develop metastases in more than one regional lymph node basin. To
      determine whether this is prognostically significant, we reviewed our experience
      with melanoma patients who had undergone regional lymphadenectomy (RLND) in two
      separate basins. RESULTS: Of 3,603 patients who underwent RLND between April 1971
      and January 1993, 406 underwent procedures in two separate basins; of these, 120
      (30%) had metastases in both basins and 124 (30%) had metastases in one basin.
      When calculated from the first positive RLND, 1-year, 3-year, and 5-year survival
      rates were 82%, 48%, and 33%, respectively, for patients with dual-basin
      involvement and 88%, 59%, and 48%, respectively, for patients with single-basin
      involvement (p = 0.0173). Median survival from the first positive RLND was 33.5
      months for dual-basin involvement and 56.6 months for single-basin involvement.
      Univariate analysis demonstrated that Breslow thickness of the primary melanoma,
      clinical status of the regional lymph nodes, number of positive RLNDs, and tumor
      burden (total number of positive lymph nodes) were significant indicators of
      survival. The patient's age and gender, the anatomic location and Clark level of
      the primary melanoma, the disease-free interval before regional metastasis, and
      the site and timing of RLNDs were not significant by univariate analysis.
      Multivariate analysis demonstrated significance for Breslow thickness, number of
      positive RLNDs, and tumor burden. CONCLUSIONS: The survival rate of melanoma
      patients with regional metastases in two lymph node basins is lower than that of
      patients with an equal tumor burden confined to a single basin. This suggests
      that primary melanomas metastasizing to more than one lymph node basin may have a
      higher metastatic potential, or that dual-basin involvement may increase the risk
      of systemic spread. We advocate lymphatic mapping, sentinel node biopsy, and
      selective lymphadenectomy as a cost-effective technique with little morbidity to
      identify and manage occult metastases in patients who have two lymph basins at
      risk.

PMID- 8985513
TI  - Multiple primary melanomas: implications for screening and follow-up programs for
      melanoma.
AB  - BACKGROUND: Once individuals are diagnosed with malignant melanoma, they are at
      an increased risk of developing another melanoma when compared with the normal
      population. METHODS: To determine the impact of an intensive follow-up protocol
      on the stage of disease at diagnosis of subsequent primary melanomas, a
      retrospective query was performed of an electronic medical record database of
      2,600 consecutively registered melanoma patients. RESULTS: Sixty-seven patients
      (2.6%) had another melanoma diagnosed at the time of presentation to the clinic
      or within 2 months (synchronous) and another 44 patients (1.7%) developed a
      second primary melanoma during the follow-up period (metachronous). For the 44
      patients diagnosed with metachronous lesions, the Breslow mean tumor thickness
      for the first invasive melanoma was 2.27 mm compared with 0.90 mm for the second
      melanoma. The first melanomas diagnosed are thicker by an average of 3.8 mm (p =
      0.008). The mean Clark level for the initial melanoma was greater than the mean
      level for subsequently diagnosed melanomas (p = 0.002). Twenty-three percent of
      the initial melanomas were ulcerated, whereas only one of the second primary
      lesions showed this adverse prognostic factor (p = 0.002). CONCLUSIONS: Once
      individuals are diagnosed with melanoma, they are in a high-risk population for
      having other primary site melanomas diagnosed and should be placed in an
      intensive follow-up protocol consisting of a complete skin examination.

PMID- 8985514
TI  - Local recurrence in breast cancer: implications for systemic disease.
AB  - BACKGROUND: Recurrence in breast carcinoma follows a pattern of growth marked by
      local, regional, or widespread dissemination. Local recurrence may be the
      harbinger of systemic disease or failure of local control. Delineation of these
      processes may have implications in treatment. METHODS: A retrospective review
      found 1,171 patients with stages I and II breast cancer from 1978 to 1990 treated
      at the City of Hope Medical Center. RESULTS: Twenty-seven percent (n = 313) of
      patients developed recurrences. These were classified as local, including chest
      wall and regional nodes (n = 40), local and distant (n = 63), and distant (n =
      210). Mean follow-up was 60 months. Multivariate analysis demonstrates tumor size
      was not different between the three groups, but the presence of positive lymph
      nodes was: local = 51%, local and distant = 78%, and distant = 64%. The disease
      free interval was longest in the local group (42 months) versus the local and
      distant group (23 months) and distant group (39 months). Median survival was
      calculated from the time of recurrence: local = 90 months, local and distant = 26
      months, and distant = 16 months. CONCLUSIONS: A group of patients with local
      recurrence have improved survival and do not develop distant disease. This group
      may benefit from aggressive surgical treatment to control local disease. These
      data suggest that a subset of breast tumors can act locally aggressive without
      metastatic potential.

PMID- 8985515
TI  - Lesions of the calvaria: surgical experience with 42 patients.
AB  - BACKGROUND: Lesions of the calvaria (cranial vault), whether benign or malignant,
      are rare, and the number that require surgical attention is very limited. During
      a 13-year period, 42 patients ranging in age from 13 to 82 years were treated
      surgically at our institution for lesions involving primarily the calvaria. The
      patients were found to have 16 benign lesions, 21 malignant lesions, and 5
      pathologically ill-defined lesions. At last follow-up, 23 patients were still
      alive. METHODS: Criteria for choosing surgery as the preferred therapeutic
      modality included (a) uncertain diagnosis; (b) benign lesions with a high
      probability of total removal; 3) malignant lesions that represented the only
      residue of a systemic malignancy that was in remission; or (d) lesions that were
      rapidly enlarging, were causing significant symptoms, or were unresponsive to
      radiation or chemotherapy. RESULTS: Preoperative needle biopsy was useful for
      some patients in establishing a definitive diagnosis and in providing the basis
      for the most effective treatment strategy. Most lesions were treated with either
      craniectomy alone (n = 16) or with craniectomy and cranioplasty (n = 26). Six of
      the 42 patients had postoperative complications. There was no operative
      mortality. CONCLUSION: This review of a series of patients with calvarial lesions
      provides an outline of the overall diagnostic workup and management of this
      unique patient population.

PMID- 8985516
TI  - p53 overexpression in squamous cell carcinoma of the esophagus.
AB  - BACKGROUND: Coastal South Carolina has a high incidence of squamous cell
      carcinoma of the esophagus (SCCE) among black residents. Overexpression and
      mutations of the p53 tumor suppressor gene have been noted in SCCE from other
      high-incidence regions. The purpose of this study was to determine the frequency
      of p53 overexpression in this region both in patients with SCCE and in normal
      subjects. METHODS: Normal and malignant tissue obtained at esophagoscopy and
      normal esophageal mucosa (NEM) from random autopsies were studied with monoclonal
      antibodies to the p53 gene product. Total cellular RNA was extracted from SCCE,
      reverse transcribed to complementary DNA, and a portion of the p53 gene was
      amplified via polymerase chain reaction and sequenced. RESULTS:
      Immunohistochemical studies on SCCE from nine patients showed that six (67%) were
      positive, two (22%) were negative, and one was indeterminate for p53
      overexpression. The corresponding normal samples showed that three (33%) had p53
      positive cells in the basal epithelial layer, whereas six did not. NEM from 18
      random forensic cases displayed p53 overexpression in seven (39%). Eight of the
      nine tumors had p53 mutations. CONCLUSIONS: p53 overexpression and mutations are
      frequently found in SCCE from patients in coastal South Carolina. Overexpression
      in normal epithelium from random autopsy cases may indicate an inherited or
      acquired predisposition in this geographic region.

PMID- 8985517
TI  - Prognostic importance of histomorphologic subclassification for epithelial thymic
      tumors.
AB  - BACKGROUND: The prognostic importance of various clinical variables (age, sex,
      association with myasthenia gravis), staging according to Masaoka, histologic
      type according to the Marino/Kirchner/Muller-Hermelink (MKM-H) classification,
      and residual tumor category (R category) was evaluated in a retrospective
      analysis. METHODS: Eighty-two patients with epithelial thymic tumors (ETTs)
      treated in the period 1969-1993 were evaluated, and archived specimens were
      histologically reclassified according to the classification of MKM-H. RESULTS:
      Age, sex, and association with myasthenia gravis were of no prognostic
      importance. The R category is of significant prognostic importance, with 5- and
      10-year survival rates of 93.6% and 87.3%, respectively, for R0 resections
      compared with 0% at 5 years for R1 and R2 resections (p < 0.001). Staging
      (Masaoka) proved to be a prognostic factor (5-/10-year survival: stage I,
      100%/90.9%; II, 95%/88.2%; III, 55.9%/46.6%; and IV, 10.8%/ 10.8%; p < 0.001).
      Histologic typing according to MKM-H is also of significant prognostic importance
      (5/10 year survival: thymomas: medullary, 100%/100%; mixed, 100%/100%,
      predominantly cortical, 68.6%/68.6%; cortical, 65.8%/65.8%; thymic carcinomas:
      well-differentiated type, 62.3%/44.5%; thymic carcinomas other than well
      differentiated type, 33.6%/26.9%; p < 0.001). Multivariate analysis demonstrated
      that staging (p < 0.001), R category (p < 0.026), and MKM-H classification (p <
      0.028) have an independent impact on survival. CONCLUSIONS: Staging (Masaoka), R
      category, and histologic classification (MKM-H) are important independent
      prognostic factors for patients with epithelial thymic tumors. Complete (R0)
      surgical resections should be the ultimate goal in the clinical management of
      patients with epithelial thymic tumors.

PMID- 8985518
TI  - Detection of local recurrence of soft-tissue sarcoma with positron emission
      tomography using [18F]fluorodeoxyglucose.
AB  - BACKGROUND: It is often difficult to detect a local recurrence of soft-tissue
      sarcomas due to disturbance of the normal anatomy by previous surgery and
      radiotherapy. The aim of this study was to assess the value of positron emission
      tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (FDG) for detecting local
      recurrences. METHODS: In the period 1992-1995, 17 patients with proven or
      suspected local recurrence of soft-tissue sarcoma were examined using FDG-PET.
      Fifteen of these patients were ultimately proven to have a recurrence. RESULTS:
      Recurrence was visualized in 14 patients (93%). Small tumors (maximum diameter
      0.5 cm) were as easily visible as large lesions (maximum diameter 20 cm). In one
      patient the PET scan was positive, but the recurrence could not be proven
      histologically. Recurrence was proven 1 year later. A recurrent low-grade
      liposarcoma was not visualized. The two patients with benign lesions had a
      negative PET scan. The mean glucose metabolic rate was calculated to be 13.2
      mumol/100 g/min (range 1.9-28.4). A correlation was found between the
      histological malignancy grade and the metabolic rate (p < 0.05; Kruskal-Wallis).
      CONCLUSION: PET with FDG is a useful addition to the diagnostic armamentarium for
      detecting local recurrence of soft-tissue sarcomas and provides an indication of
      the malignancy grade of the recurrent lesion.

PMID- 8985519
TI  - Angiographic response of locally advanced soft-tissue sarcoma following
      hyperthermic isolated limb perfusion with tumor necrosis factor.
AB  - BACKGROUND: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis
      factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and melphalan is
      associated with a dramatic anti-tumor effect in which the neo-vascularization of
      the tumor is supposed to be the major target. The aim of the present study was to
      correlate the angiographic findings with the pathological response in patients
      undergoing HILP for locally advanced soft-tissue sarcoma. PATIENTS AND METHODS:
      Twenty-five patients, 14 male and 11 female, mean age 47 years (range 18-80) were
      studied. Angiographies were performed before and a median period of 7 weeks
      (range 4-14 weeks) after HILP. Eight weeks after perfusion, the residual tumor
      mass was resected and pathologically examined. The changes in tumor
      vascularization after treatment were scored and compared with the pathological
      response. RESULTS: All baseline angiograms showed a hypervascular tumor. After
      HILP, a normal angiography result (NA) was observed in 18 patients (72%) and an
      abnormal angiography result (AA) was observed in seven patients (28%). All
      patients with an NA showed a pathologically complete response (pCR) or a
      pathological partial response with > 90% necrosis of the tumor. Of seven patients
      with an AA, pathological examination showed a pCR in one patient, 10-50% viable
      tumor volume in four patients, and no pathological response after perfusion in
      two patients. A good correlation was seen between angiographic and pathological
      classification (p < 0.001). CONCLUSION: An angiography performed after
      hyperthermic isolated limb perfusion with TNF-alpha and melphalan provides a good
      indication, regardless of whether a good pathological response is expected.

PMID- 8985520
TI  - Transduction of murine and human tumors using recombinant adenovirus vectors.
AB  - BACKGROUND: Most cytokine-based cancer gene therapy clinical trials have used
      labor-intensive, retrovirus-mediated strategies resulting in unpredictable gene
      expression. Recombinant AdV vectors were evaluated for easier, more reproducible
      gene transfer into 12 human melanoma, 2 murine fibrosarcomas, and 8 other tumor
      cell lines. METHODS: AdV vectors contained a reporter (Escherichia coli beta
      galactosidase or firefly luciferase) or cytokine gene (human interleukin-2 [IL-2]
      or IL-7). Transduction efficiencies and expression levels were assessed by
      histochemical staining, flow cytometry, polymerase chain reaction, fluorometry,
      and enzyme-linked immunosorbent assay. Tumorigenicity was determined by
      subcutaneous injection of cells into syngeneic mice. RESULTS: All cell lines
      studied were transduced with AdV. Most cell lines exhibited 100% transduction
      efficiencies (by flow cytometry) at multiplicities of infection (MOI) epsilon 10.
      Gene expression correlated linearly with MOI, but a cytopathic effect was
      observed at MOI > 100 with all vectors. Nanogram gene expression levels were
      routinely achieved. Irradiation (30 Gy) minimally affected expression levels.
      Tumorigenicity of AdV-IL-2-transduced fibrosarcoma cells in mice was inversely
      related to IL-2 production. A majority of mice that rejected their tumor
      challenge were immune to tumor rechallenge. CONCLUSIONS: E1-deleted AdV vectors
      may prove useful in generating tumor vaccines ex vivo with high, transient
      cytokine expression levels.

PMID- 8985521
TI  - Importance of race on breast cancer survival.
AB  - BACKGROUND: Breast cancer survival has been shown to be significantly less among
      black women than white women. The reason for this difference in survival is
      unclear. METHODS: Data were obtained retrospectively on 439 women seen between
      1985 and 1993 based on a detailed chart audit. The impact of race and several
      known prognostic factors on overall survival, time to relapse, and survival after
      relapse were studied. RESULTS: Black women with breast cancer were found to have
      a greater risk of recurrence, shorter overall survival, and shorter survival
      after relapse than did white women. Black patients were found to be younger and
      have higher stage of disease and lower hormone receptor levels than were white
      patients. After adjustment for menopausal status and disease stage, a significant
      independent effect of race was observed on overall survival but not risk of
      recurrence. In multivariate analysis, a significant interaction was observed
      between race and age in some models. Survival after recurrence of disease was
      lower among black than white women after adjustment for menopausal status and
      estrogen receptor level. CONCLUSION: Black women experience shorter survival
      times than do white women, including a shorter survival time after disease
      recurrence. Breast cancer in black women is associated with younger age, higher
      stage at presentation, and low hormone receptor levels. After adjustment for
      known prognostic factors, race remains a significant independent predictor of
      breast cancer survival.

PMID- 8985523
TI  - Childhood neuromuscular disorders: a decade's experience in Saudi Arabia.
AB  - The study describes the pattern of childhood neuromuscular disorders seen in a
      decade (1982-1992) at King Khalid University Hospital, Riyadh, Saudi Arabia.
      Similar data are scanty outside Europe and North America, and lacking in Saudi
      Arabia. Eighty-four children (< or = 16 years) were assigned to an entity of
      neuromuscular disease following review of the clinical, biochemical and
      neurophysiological data, and after re-examination of the histological and
      histochemical features of the muscle biopsies. Of the 84 ascertained cases, 40
      (48%) had different forms of muscular dystrophy (MD), 26 (31%) had one of the
      various types of spinal muscular atrophy (SMA) and two (2.4%) hereditary motor
      and sensory neuropathy type I. The rest were miscellaneous cases including one
      (1.2%) with dermatomyositis. Of the dystrophies, severe childhood autosomal
      recessive muscular dystrophy (SCARMD) was more prevalent (30%) than Duchenne type
      (25%), conforming with observations from North African countries known to have a
      high incidence of consanguineous marriages. Family history of other cases of
      SCARMD included three males and three females, one of whom died at 15 years, and
      consanguinity was evident in 63%. Congenital MD, inherited in an autosomal
      recessive pattern, was also common (30%). A history of consanguinity was present
      in 55%. Of the 26 cases of SMA, type I (Werdnig-Hoffman disease) was the most
      prevalent (69%). Consanguinity was ascertained in 65% of SMA families and
      histories revealed another 14 affected siblings. Autosomal recessive forms seem
      to constitute the bulk of neuromuscular disorders in Saudi Arabia.

PMID- 8985522
TI  - Value of laboratory tests in monitoring acute regional toxicity after isolated
      limb perfusion.
AB  - BACKGROUND: Severe limb toxicity following isolated limb perfusion (ILP) can lead
      to compartmental compression syndrome and severe rhabdomyolysis, occasionally
      necessitating amputation of the affected limb. We determined whether laboratory
      tests for muscle damage and inflammation could predict impending limb toxicity.
      METHODS: All 184 consecutive ILPs performed in our institute from 1988 to 1994
      were included in this study. Creatine kinase (CK), lactate dehydrogenase (LDH),
      aspartate aminotransferase (ASAT) and white blood cell (WBC) counts were
      determined on post-ILP days 1-4, 6, 8, and 15. RESULTS: "Late peak" CK patterns,
      characterised by a peak on or after the 5th post-perfusion day, were strongly
      associated with severe limb toxicity (p < 0.001). Severe toxicity did develop in
      40% of the limbs when CK values exceeded 1000 IU/L on the 2nd to 5th post-ILP day
      (p < 0.001). There was a correlation between the peak CK and the individual
      grades of toxicity (r = 0.6, p < 0.001). Serum LDH and ASAT values peaked 2.9 and
      3.4 days after the CK peak respectively. Severe limb toxicity was statistically
      significantly associated with higher WBC counts from the 2nd post-ILP day
      onwards. CONCLUSIONS: CK values exceeding 1000 IU/L after the 1st and WBC counts
      increasing after the 2nd post-ILP day could be predictors of impending limb
      toxicity. These patients should be observed closely for signs of compartmental
      compression syndrome and severe rhabdomyolysis.

PMID- 8985524
TI  - Mefloquine in infants and young children.
AB  - In an area where multi-drug resistance in Plasmodium falciparum is a particular
      problem, more than 500 children under 5 years of age weighing > 5 kg were treated
      with mefloquine, either alone or combined with an artemisinin derivative, and
      followed up for a minimum of 28 days. The principal adverse effect was vomiting
      and this was associated with reduced efficacy of treatment (even when treatment
      was repeated). Later adverse effects occurred less frequently than in adults.
      There was no serious toxicity and, in particular, there were no neuropsychiatric
      side-effects. The high dose of mefloquine (25 mg/kg) required in this area is
      well tolerated by young children. It should be given in a divided dose of 15
      mg/kg initially, followed by 10 mg/kg > or = 12 hours later.

PMID- 8985525
TI  - Henna (Lawsonia inermis Linn.) inducing haemolysis among G6PD-deficient newborns.
      A new clinical observation.
AB  - Over a 10-year period, 15 glucose-6-phosphate dehydrogenase (G6PD)-deficient male
      newborns were admitted to Al-Jahra Hospital with acute haemolysis a few days
      after applying henna dye over the body, which is a unique Bedouin tribal practice
      to celebrate the arrival of the first-born boy. Laboratory investigations
      revealed significant anaemia, reticulocytosis and indirect hyperbilirubinaemia
      among the index newborns as compared with controls (p < 0.001). The mean (SD)
      haemoglobin concentration in index patients was 113.4 (13.4) g/l vs 171.2 (11.2)
      g/l in controls, reticulocytic count 13.8% (4.2%) vs 1.4% (0.74%), and indirect
      bilirubin 382.8 (58.7) mumol/l vs 63.7 (61.4) mumol/l. G6PD-deficient newborns
      with haemolysis linked to henna application had delayed age at presentation and a
      higher reticulocytic count and hyperbilirubinaemia compared with non-henna
      induced haemolysis (p < 0.05). Percutaneous henna absorption is well recognized
      and clinical findings support the harmful effect of henna on G6PD-deficient red
      blood cells. A local health education programme has been established to prevent
      the use of henna dye in infancy.

PMID- 8985526
TI  - Bacteriuria in children attending a primary health care clinic: a prospective
      study of catheter stream urine samples.
AB  - Urinary tract infection (UTI) in infancy and childhood has received scant
      attention at primary health care (PHC) level, rarely featuring as one of the
      common diseases. In a prospective study conducted at a PHC clinic, 16 of 94
      children (17%) from whom urine was collected by strict aseptic catheterization
      had bacteriuria (BU). Twelve of these had associated leucocyturia (> 5 WBC/HPF).
      The median age of those with BU was 9 months (range 1-30 months). BU rarely
      occurred in isolation (6%), but was most often detected in association with acute
      respiratory infection (43%) and acute diarrhoea (19%). No association of BU with
      mild malnutrition was detected in the 50% of children who were underweight for
      age. Gram-negative pathogens accounted for 14 cases (87.5%). These pathogens were
      resistant to commonly recommended antibiotics for UTI. Only five cases of BU
      returned for follow-up at 3 months; no abnormalities were detected on repeat
      catheter urine samples, urinary tract ultrasonography, voiding cystourethrogram
      and DMSA studies in them. From these and other findings we conclude that BU is
      probably often present in young children with common diseases attending PHC
      centres in developing countries. Further studies are required to establish
      exactly the role these pathogens play in the pathogenesis of UTI.

PMID- 8985527
TI  - Therapeutic aspects of typhoidal salmonellosis in childhood: the Karachi
      experience.
AB  - We evaluated the response to therapy in a series of 876 children consecutively
      admitted to The Aga Khan University Hospital with culture-proven typhoid,
      including 281 cases infected with multi-drug-resistant (MDR) strains. Among
      sensitive isolates there was no significant difference in cure rates, failure
      rates and time to defervescence with either ampicillin or chloramphenicol. Of the
      217 children with MDR typhoid who received therapy with third-generation
      cephalosporins, the outcome was significantly better with intravenous ceftriaxone
      compared with cefotaxime. Despite comparable cure rates, the time to
      defervescence was significantly longer among MDR strains treated with ceftriaxone
      versus sensitive strains (mean (SD): 7.2 (3.4) versus 6.3 (29) days; p < 0.05).
      Earlier recognition and introduction of appropriate second-line therapy has
      allowed us to reduce the case fatality rates of typhoid to under 1%. Although a
      14-day course of ceftriaxone can be used successfully to treat most children
      hospitalized with MDR typhoid, there is a need to evaluate the role of short
      course therapy or alternative therapeutic agents.

PMID- 8985528
TI  - Clinical problems in measles case management.
AB  - Measles remains one of the leading causes of childhood morbidity and mortality in
      developing countries. The World Health Organization has identified effective case
      management as one of the specific strategies to reduce the burden of this
      disease. The purpose of this article is to review the aetiology, natural history,
      treatment and outcome of the common clinical problems associated with measles
      with a view to identifying possible deficiencies in case management.
      Complications such as pneumonia, diarrhoea, croup and malnutrition have been well
      defined in terms of their relative contribution to morbidity and mortality.
      However, there are few published data on the aetiology and natural history of
      these specific complications. Such data are crucial for rational case management
      strategies. Data on treatment of measles and its complications are limited and
      the role of antibiotic prophylaxis and therapy is unclear. The only specific
      research focus on case management during the last decade has been vitamin A
      therapy. There is a continuing need for community and hospital-based studies on
      the natural history of measles and its complications, the aetiology of these
      complications and intervention strategies that will improve measles case
      management.

PMID- 8985529
TI  - Protein energy malnutrition, vitamin A deficiency and night blindness in
      Bangladeshi children.
AB  - The occurrence of night blindness and serum vitamin A concentrations among
      children in rural Bangladesh were studied in relation to protein energy
      malnutrition, dietary habits and intake of vitamin A capsules. In 1992, 124 night
      blind children were registered in a cross-sectional survey in the northern part
      of Bangladesh, and age-, sex- and neighbourhood-matched controls were selected.
      Of these, the first reported night-blind child from a household (n = 105) and
      their controls were included in the analyses. Our results showed that night
      blindness was associated with protein energy malnutrition when using the mid
      upper arm circumference (MUAC) as a measure of nutritional status. The odds ratio
      for a confirmed diagnosis of night blindness among children with a MUAC < 80% of
      the reference versus normal children was 5.4 (CI 1.9-15.5). Low MUAC was
      associated with low intake of beta-carotene-rich and vitamin A-containing foods
      as well as with low serum vitamin A in the total series of cases and controls.
      This may indicate that night blindness is only one aspect of the general protein
      energy malnutrition problems in this population. We therefore suggest that
      measures to prevent vitamin A-related morbidity and mortality should include
      improvement of the general diet with increased consumption of dietary vitamin A.

PMID- 8985530
TI  - Maternal factors influencing the occurrence of low birthweight in northern
      Vietnam.
AB  - The relationship between the birthweight of newborn infants and their mothers'
      health characteristics as well as socio-economic status were studied in 1474
      consecutive deliveries from eight areas in the delta region of north Vietnam. The
      results showed that the proportion of low birthweight (LBW) infants varied from
      7.9% to 12.5%. Body mass index (BMI) of the mothers, good nutrition during
      pregnancy and maternity leave before delivery were negatively associated with the
      occurrence of LBW. The association between chronic energy deficiency (low BMI)
      and LBW was seen only among the farming women. Measures should be taken to reduce
      the workload and to supply sufficient food for pregnant women, and special
      priority should be given to rural areas.

PMID- 8985531
TI  - Hepatitis C virus infection in two groups of paediatric patients: one maintained
      on haemodialysis and the other on continuous ambulatory peritoneal dialysis.
AB  - Seropositivity to hepatitis C virus (HCV) was evaluated in three groups of Saudi
      children. One group (n = 18) was maintained on haemodialysis and another group (n
      = 21) on continuous ambulatory peritoneal dialysis (CAPD). The third group were
      community-based normal controls. The prevalence of antibody to HCV (anti-HCV) in
      children on haemodialysis (11.2%) was significantly higher than that in the
      control group (n = 220) (1.4%; p = 0.056). There was no significant difference in
      the prevalence of anti-HCV between children on CAPD (4.8%) and the control group
      (1.4%; p = 0.244). Among ten children on haemodialysis who were anti-HCV-negative
      4 years earlier, two seroconverted and the seroconversion was not due to
      transfused blood but was most likely due to environmental contamination. This is
      the first report on the prevalence of anti-HCV in children maintained on CAPD.
      The results of the study emphasize the need for separate dialysis machines for
      anti-HCV-positive patients. It seems that CAPD therapy might reduce transmission
      of HCV but a large number of CAPD patients will need to be studied to confirm
      superiority to haemodialysis in this respect.

PMID- 8985532
TI  - Paediatric upper gastro-intestinal endoscopy in developing countries.
AB  - A retrospective study of 200 endoscopies performed on 168 children (90 girls and
      78 boys) aged 3 months to 18 years (median 6 years) is reported. All procedures
      were completed successfully in an adult endoscopy unit in a comprehensive health
      centre. Most children of less than 6 months and above 12 years of age needed no
      intravenous sedation. One child developed respiratory depression and was
      successfully resuscitated. Indications for endoscopy were: small intestinal
      biopsy, 78 (46%); recurrent abdominal pain, 40 (24%); acute epigastric pain, 13
      (8%); persistent vomiting, 12 (7%); haemorrhage, 10 (6%); caustic substance
      ingestion, six (4%); and dysphagia, four (2%) children. Positive diagnoses were
      obtained in 123 (62%) procedures. Coeliac disease (26 cases) was the most common
      histological diagnosis, followed by gastritis (19 cases), oesophagitis (18
      cases), duodenitis (16 cases), duodenal ulcer (11 cases), hiatus hernia (six
      cases), gastric ulcer (three cases) and oesophageal stricture (two cases). Where
      specialized paediatric endoscopy units are not feasible, e.g. in developing
      countries, endoscopic services for children can be safely provided by paediatric
      endoscopists as part of an adult endoscopy service, provided that suitable
      resuscitation equipment is available and the necessary modifications to meet the
      medical and psychological needs of children and their parents are taken into
      consideration.

PMID- 8985533
TI  - Rett syndrome in Saudi Arabia: report of six patients.
AB  - Six girls (five Saudis and one Sudanese) aged between 3.5 and 12 years
      demonstrated the classic features of Rett syndrome (RS), including developmental
      regression with dementia, loss of acquired speech and hand function, and
      stereotypic hand movements. Myoclonic seizures were observed in two of them.
      Electroencephalography showed diffuse slowing in three cases generalized
      epileptic discharges in one, and normal findings in two. Cranial computed
      tomography revealed normal findings, except in the 12-year-old girl who had mild
      bilateral frontal lobe atrophy. Except for mildly elevated blood ammonia in three
      patients, associated with slightly elevated blood lactate in two of them, results
      of neurometabolic screening tests were normal. There are, as yet, no laboratory
      markers pathognomonic for RS. Hence, adherence to current diagnostic criteria is
      essential. To prevent unnecessary and costly investigations, especially in
      developing countries, wider knowledge of the clinical features of the syndrome is
      warranted.

PMID- 8985534
TI  - Neonatal BCG vaccination and tuberculin skin sensitivity among schoolchildren of
      the United Arab Emirates.
AB  - A cross-sectional survey of 785 schoolchildren living in the Al Ain region was
      undertaken between January and June 1994 to assess the effect of neonatal BCG
      vaccination on tuberculin sensitivity and to study the risk of exposure to
      tuberculosis in the same population. A documented history of BCG vaccination was
      obtained in 547 (69.7%) schoolchildren. The prevalence of a 10 mm or greater
      induration of tuberculin skin reactivity varied from 8% in unvaccinated to 11.5%
      among vaccinated children. This was not statistically significant. Children
      living in urban areas irrespective of vaccination status had a higher rate of
      tuberculin reactivity than those living in rural areas (relative risk 5.77; 95%
      confidence interval 1.85-18.00; p < 0.0004). The pattern and rate of tuberculin
      sensitivity were similar among the other socio-demographic standards
      investigated. Earlier BCG vaccination had no effect on subsequent tuberculin
      sensitivity of either negative (0.4 mm), intermediate (5-9 mm) or positive (> or
      = 10 mm) type skin reactions. It is concluded that the risk of exposure to
      tuberculous infection is several times higher among children living in urban
      areas than among those living in a rural environment. Earlier BCG vaccination
      should not interfere with diagnostic tuberculin skin sensitivity and is still a
      useful tool in assessing the risk of tuberculous infection in such populations.

PMID- 8985535
TI  - Hypertriglyceridaemia-thalassaemia syndrome.
AB  - We report a rare association of beta-thalassaemia major and hypertriglyceridaemia
      in a 4-month-old boy. The possible significance of this association is
      highlighted.

PMID- 8985537
TI  - Tuberculous anterior neck mass simulating goitre.
AB  - A 13-year-old Saudi boy was referred to the paediatric endocrinology clinic for
      evaluation of rapidly progressive goitre with weight loss of 6 months duration. A
      clinical diagnosis of possible thyroid malignancy was made. On exploration the
      mass was found to be tuberculous in origin, attached to the thyroid gland, and
      responded to partial excision and anti-tuberculous chemotherapy. Tuberculosis
      should be considered in the differential diagnosis of anterior midline neck
      masses.

PMID- 8985536
TI  - Pneumocystis carinii and cytomegalovirus infections in severely ill, HIV-infected
      African infants.
AB  - Unlike in the industrialized world, in which Pneumocystis carinii and
      cytomegalovirus (CMV) are major respiratory opportunistic organisms, the causes
      of severe pneumonia, which accounts for much of the mortality in HIV-infected
      infants in developing countries, are not known, although tuberculosis has been
      associated with HIV in adults. We report on post-mortem lung and liver biopsies
      obtained soon after death from 36 HIV-infected infants and 36 HIV-uninfected
      matched controls who had been admitted with severe pneumonia to an ICU. Nineteen
      of the HIV-infected infants were classified by WHO criteria as having AIDS and 17
      'symptomatic HIV'. P. carinii and CMV were detected significantly more frequently
      in lung tissue from the AIDS patients (14 of 18 samples tested, p < 0.01; 14 of
      18 samples tested, p < 0.01, respectively) as compared with matched controls. P.
      carinii was detected in two of 13 lung biopsies from symptomatic HIV infants, but
      in none of the controls. Lung tissue obtained from AIDS patients had P. carinii
      and CMV more frequently (p < 0.01, p < 0.01, respectively) than that from
      symptomatic HIV patients. CMV was also detected in excess in liver tissue from
      AIDS infants (five of 18 samples) as compared with that from symptomatic HIV (0
      of 16; p = 0.03) and matched controls (two of 34; p = 0.04). Ante-mortem
      investigations revealed more CMV infections in AIDS patients (four of 19) than in
      matched controls (0 of 36; p < 0.01). Tuberculosis was detected in post-mortem
      lung tissue from only one patient with symptomatic HIV infection. The finding
      that pathogens (P. carinii, CMV) most frequently detected in seriously ill
      African infants with HIV/AIDS are similar to those in their counterparts from
      industrialized countries has implications for improved management in the former.

PMID- 8985538
TI  - A computerized induction analysis of possible co-variations among different
      elements in human tooth enamel.
AB  - In recent decades software tools in the area of artificial intelligence have
      rapidly developed for use in personal computers. Interactive rule induction
      utilizing mathematical algorithms has become a powerful tool in data analysis and
      in making rules and patterns explicit. Data from a Secondary Ion Mass
      Spectrometry (SIMS) elemental analysis of human dental enamel were used to
      elucidate co-variations between certain elements. A co-variation analysis was
      performed employing a computerized induction analysis program, as well as a
      neural network program. Both analyses, confirming each other, revealed co
      variations between certain elements in dental enamel in addition to exclusion of
      data of no importance for chosen outcomes. The results are presented in
      hierarchic diagrams, in which the importance for every specific element is given
      by its position and level in the diagram (decision tree). From the results it
      became evident that elements such as chlorine and sodium expressed a high co
      variation level. Similarly fluorine and potassium co-varied, as well as magnesium
      and the trace element strontium. It was demonstrated that data from an elemental
      analysis could be processed by an induction analysis to reveal co-variations
      between certain elements in tooth enamel. The biological significance of these
      data is not fully understood, and further analyses in the field are needed.

PMID- 8985539
TI  - Deep assessment of machine learning techniques using patient treatment in acute
      abdominal pain in children.
AB  - Learning from patient records may aid knowledge acquisition and decision making.
      Existing inductive machine learning (ML) systems such us NewId, CN2, C4.5 and
      AQ15 learn from past case histories using symbolic and/or numeric values. These
      systems learn symbolic rules (IF... THEN like) which link an antecedent set of
      clinical factors to a consequent class or decision. This paper compares the
      learning performance of alternative ML systems with each other and with respect
      to a novel approach using logic minimization, called LML, to learn from data.
      Patient cases were taken from the archives of the Paediatric Surgery Clinic of
      the University Hospital of Crete, Heraklion, Greece. Comparison of ML system
      performance is based both on classification accuracy and on informal expert
      assessment of learned knowledge.

PMID- 8985541
TI  - Change for better?

PMID- 8985540
TI  - Utilizing temporal data abstraction for data validation and therapy planning for
      artificially ventilated newborn infants.
AB  - Medical diagnosis and therapy planning at modern intensive care units (ICUs) have
      been refined by the technical improvement of their equipment. However, the bulk
      of continuous data arising from complex monitoring systems in combination with
      discontinuously assessed numerical and qualitative data creates a rising
      information management problem at neonatal ICUs (NICUs). We developed methods for
      data validation and therapy planning which incorporate knowledge about point and
      interval data, as well as expected qualitative trend descriptions to arrive at
      unified qualitative descriptions of parameters (temporal data abstraction). Our
      methods are based on schemata for data-point transformation and curve fitting
      which express the dynamics of and the reactions to different degrees of
      parameters' abnormalities as well as on smoothing and adjustment mechanisms to
      keep the qualitative descriptions stable. We show their applicability in
      detecting anomalous system behavior early, in recommending therapeutic actions,
      and in assessing the effectiveness of these actions within a certain period. We
      implemented our methods in VIE-VENT, an open-loop knowledge-based monitoring and
      therapy planning system for artificially ventilated newborn infants. The
      applicability and usefulness of our approach are illustrated by examples of VIE
      VENT. Finally, we present our first experiences with using VIE-VENT in a real
      clinical setting.

PMID- 8985542
TI  - Cataract surgery in Australia 1985-94.
AB  - BACKGROUND: Cataract surgery is the most common form of major ophthalmic surgery
      in Australia and a common surgical procedure among the elderly. The purpose of
      this report is to compile the numbers and rates of cataract extractions and
      implant of IOLs over the period 1985-94 for Australia. METHODS: Data were
      obtained for public and private cataract extractions and IOL implants from state
      and territory ministries of health and from the Health Insurance Commission. The
      data relating to cataract surgery were compared with the growth in the proportion
      of elderly people in the population. RESULTS: The number of cataract extractions
      has increased by 2.6 times over the ten-year period to 67,459 in 1994 and IOL
      implants have increased by 2.9 times over the same period to 70,084. The increase
      in the elderly population for the period was 1.3 times so that there is a
      relative doubling in the rate of surgery. The proportion of public patients has
      risen from 19% to 28% from 1985 to 1994. CONCLUSIONS: The numbers of cataract
      extractions and IOL implants was increased at double the rate expected from the
      growth in the elderly population. Advances in microsurgery and IOL technology
      have resulted improved outcomes and have created a greater patient demand. The
      improved outcomes have also lead to ophthalmologists recommending cataract
      surgery at better visual acuity levels than previously.

PMID- 8985543
TI  - Cost effectiveness of cataract surgery. A comparison of conventional
      extracapsular surgery and phacoemulsification at Flinders Medical Centre.
AB  - PURPOSE: To compare the cost of conventional extracapsular cataract surgery and
      phacoemulsification at Flinders Medical Centre. METHODS: The costs of the two
      forms of cataract surgery were assessed over a 12-month period. During this
      period 410 cataract operations were performed. SETTING: The cataract surgery was
      carried out in a dedicated day surgery unit in a teaching hospital. OUTCOME
      MEASURE: The direct, indirect and tangible costs were measured. RESULTS:
      Conventional extracapsular cataract surgery with posterior chamber lens implant
      costs $1000.85 and phacoemulsification with lens implantation costs $1231.00.
      CONCLUSIONS: Although conventional extracapsular surgery generates slightly lower
      costs than phacoemulsification, the cost difference is small. In generating these
      figures, some assumptions must be made and the real difference may prove to be
      less than this.

PMID- 8985545
TI  - Mobile retinal photography. A means of screening for diabetic retinopathy in
      aboriginal communities.
AB  - BACKGROUND: Mobile fundus photography undertaken by Aboriginal health workers has
      been suggested as a practical and effective method of screening for diabetic
      retinopathy among Aboriginal and Torres Strait Islander communities. METHODS: A
      pilot study was undertaken to demonstrate that interpretable colour slides of the
      retina could be produced by Aboriginal health workers trained over a two-week
      period. RESULTS: Of 47 subjects, 36 (76.6%) had interpretable retinal
      photographs. CONCLUSIONS: These findings warrant further evaluation as to the
      benefits and cost effectiveness of mobile retinal photography.

PMID- 8985544
TI  - Surgery for refractory glaucoma.
AB  - PURPOSE: To determine the surgical outcome of mitomycin trabeculectomy in
      patients with refractory glaucoma. METHODS: Sixty-six eyes of 52 patients with
      refractory glaucoma underwent mitomycin trabeculectomy. Mitomycin was applied for
      five minutes only once during trabeculectomy. The follow-up period was six to 61
      months. RESULTS: Cumulative success probability was calculated using Kaplan-Meier
      life-table analysis assuming the cut-off postoperative IOP to be 20 mmHg or IOP
      reduction by at least 20% in eyes with preoperative IOP 24 mmHg. At the end of 61
      month follow-up the success probability was 80% +/- 6% without postoperative
      ocular hypotensive medication (complete success) and was 95% +/- 3% regardless of
      postoperative antiglaucoma medication (overall success), respectively.
      CONCLUSION: The data suggest that mitomycin trabeculectomy is efficacious in
      reducing IOP in patients with refractory glaucoma.

PMID- 8985546
TI  - Results of anterior transposition of the inferior oblique.
AB  - PURPOSE: We present the results of anterior transposition of the inferior oblique
      in a series of patients with inferior oblique overaction and dissociated vertical
      deviation (DVD). PATIENTS AND METHODS: We performed a retrospective study of 37
      procedures on 21 patients who had unilateral or bilateral inferior oblique
      anterior transpositions. Before surgery, patients had +1 to +3 inferior oblique
      overaction and +1 (< 10 PD) or +2 (10 PD-20 PD) degree of DVD. The inferior
      oblique insertion was transposed to between 2 mm posterior to and 2 mm anterior
      to the temporal border of the inferior rectus insertion. Mean follow-up period
      was 27 months. RESULTS: Incidence of inferior oblique overaction of +2 or more
      was reduced from 84% before surgery to 16% at last postoperative assessments.
      Some 43% of eyes had no inferior oblique overaction and 86% had an improvement in
      the degree of inferior oblique overaction. At last assessments, 57% of eyes had
      no evidence of DVD and 68% of eyes had no evidence of DVD or an improvement in
      the degree of DVD. No patient who had unilateral anterior transposition developed
      hypotropia in primary position and there was no evidence of inferior oblique
      underaction in any patient at last assessment. Three patients requiring repeat
      inferior oblique surgery are discussed, including one patient who developed a
      large Y-pattern exotropia after bilateral anterior transposition of the inferior
      obliques. CONCLUSIONS: Inferior oblique anterior transposition has a place in the
      treatment of coexistent inferior oblique overaction and dissociated vertical
      deviation.

PMID- 8985548
TI  - Idiopathic sectoral corneal endotheliitis.

PMID- 8985547
TI  - Evaluation of photoscreener instruments in a childhood population. 1. Otago
      photoscreener and Dortmans videophotorefractor.
AB  - OBJECTIVE: To evaluate two photoscreeners in a childhood population. STUDY
      DESIGN: Double-masked study. SUBJECTS AND METHOD: One hundred and thirteen
      children aged between 11 and 44 months with either normal vision or known visual
      disorders were photoscreened without cycloplegia by the Otago and Dortmans
      (prototype) photoscreeners. Each child had a full ophthalmological examination
      either on the day of screening or in the proceeding six months. Photoscreen
      images were reviewed by an independent observer for indicators of amblyopiogenic
      risk factors, and compared to the full ophthalmological examination to determine
      sensitivity and specificity for each instrument. RESULTS: The Otago photoscreener
      returned a sensitivity of 70% and specificity of 82% for the detection of
      amblyopiogenic risk factors. The Dortmans photoscreener returned a sensitivity of
      70% and specificity of 90%. Both photoscreeners were portable and easily
      operated. CONCLUSION: Children can be screened successfully for amblyopiogenic
      risk factors with these photoscreening systems. Further evaluation is required to
      determine specificity in a normal population. This would also provide information
      on the potential usefulness of photoscreeners in a cost effective childhood
      vision screening program.

PMID- 8985549
TI  - Intralenticular metallic foreign body.
AB  - BACKGROUND: Intralenticular metallic foreign bodies may be well tolerated for
      many years. CASE REPORT: A 24-year-old caucasian man was referred with an
      intralenticular metallic foreign body present in the left eye for five days.
      Following initial treatment with topical steroid and antibiotic, the lens
      remained clear and visual acuity normal. Two years later the left eye developed
      an anterior uveitis, with reduced vision. A left phacoemulsification lens
      extraction with removal of the intralenticular foreign body and insertion of a
      posterior chamber intraocular lens was performed. CONCLUSION: Management of
      intralenticular metallic foreign bodies may be conservative till intraocular
      inflammation or cataract develops.

PMID- 8985550
TI  - Early resolution of premacular haemorrhage following Nd:YAG laser photodisruption
      of posterior hyaloid.

PMID- 8985551
TI  - Association of keratoconus with granular corneal dystrophy.
AB  - A 23-year-old woman presented with a history of reduced vision and foreign body
      sensation in both her eyes. Ocular examination revealed the simultaneous presence
      of bilateral keratoconus and granular corneal dystrophy. To our knowledge,
      bilateral concurrent occurrence of keratoconus and typical granular corneal
      dystrophy has not been reported previously. In such a case, penetrating
      keratoplasty performed for keratoconus may also carry the risk of recurrence of
      the granular dystrophy.

PMID- 8985553
TI  - Merkel cell tumour occurring simultaneously in the upper and lower eyelids.
AB  - PURPOSE: To highlight an unusual presentation of two Merkel cell tumours in the
      same patient. RESULT: We report a case of two Merkel cell tumours occurring
      simultaneously in the upper and lower eyelids of an elderly woman, a unique
      occurrence. Wide local resection and reconstruction resulted in microscopic
      clearance of the tumours. Lymphatic spread was detected, a common feature. She
      had previously undergone excision of a similar lesion from the lower eyelid.
      CONCLUSION: Merkel cell tumour is a rare tumour of the elderly that often locally
      recurs and metastaseses early. Treatment consists of wide local excision with or
      without adjuvant radiotherapy. Juxtaposing lesions on the eyelids have not been
      previously reported. We postulate that this patient showed local recurrence and a
      new tumour of the upper eyelid simultaneously.

PMID- 8985552
TI  - Coexistent orbital and cerebellar venous anomalies in linear sebaceous naevus
      syndrome.
AB  - BACKGROUND: Orbital venous anomalies can result in significant morbidity and have
      been reported in association with other venous anomalies, some with the potential
      for serious complication. METHODS/RESULTS: We present a case of an orbital venous
      anomaly coexistent with a large cerebellar venous angioma and a linear sebaceous
      naevus. Clinical features, associations, complications and management principles
      are presented. CONCLUSION: Upon clinical recognition of an orbital venous
      anomaly, brain imaging and appropriate clinical assessment should be considered
      in light of the possibility of coexistence of potentially life-threatening
      lesions.

PMID- 8985555
TI  - A simple snare for transscleral fixation of dislocated intraocular lenses.
AB  - PURPOSE: The construction and use of a surgical snare in retrieving and securing
      posterior chamber intraocular lenses is described. METHODS: The snare consists of
      a 10-O polypropylene suture threaded into a 25-gauge retrobulbar needle. This is
      used after a pars plana vitrectomy to retrieve the dislocated intraocular lens.
      The needle attached to the polypropylene suture is used to secure the lens haptic
      1.5 mm behind the limbus. Two snares are used to secure the two lens haptics.
      CONCLUSIONS: The snare is easy to make with readily available materials. The use
      of this snare involves less intraocular and extraocular manipulations than other
      described methods.

PMID- 8985554
TI  - Disc drusen: a headache for child and clinician.

PMID- 8985556
TI  - Congenital ptosis: results of surgical management.

PMID- 8985557
TI  - TPA for sclerostomy occlusion.

PMID- 8985558
TI  - Phacoemulsification using a can-opener capsulotomy.

PMID- 8985559
TI  - Patient satisfaction with time use in audiological consultations.
AB  - An analysis of how time was used in and around 60 consultations was carried out
      for the purpose of exploring the relationship of time use to patient
      satisfaction. Sixty patients across two practice settings were surveyed,
      immediately following their interaction with the audiologist, regarding
      satisfaction with the consultation. Satisfaction was measured via: (1) a four
      point scale, which yielded a satisfaction rating; and (2) a check list of
      satisfaction with 11 aspects of the consultation, which yielded a satisfaction
      score. Satisfaction ratings and scores were correlated significantly (rs = 0.76
      corrected for ties, P = 0.0001). The majority of patients were either 'very
      satisfied' (63%) or 'satisfied' (31.6%) with the consultation experience.
      Temporal pictures of the consultations of 'very satisfied', 'satisfied' and
      'dissatisfied' patients were clearly different. For the present sample it
      appeared that patient satisfaction ensued when the total consultation time was
      equal to or exceeded 0.6 of the sum of total consultation time and the time spent
      waiting at the clinic immediately prior to the consultation. Regression analyses
      showed that of the temporal variables studied, total consultation time (TCT) and
      the amount of time waiting immediately pre consultation (WT) contributed most to
      the variation in patient satisfaction ratings and scores. Forty-two per cent of
      the variance in satisfaction ratings and 36% of the variance in satisfaction
      scores could be explained by TCT/(WT + TCT).

PMID- 8985560
TI  - Patterns of hearing recovery in idiopathic sudden sensorineural hearing loss.
AB  - Patterns of hearing recovery in idiopathic sudden sensorineural hearing loss
      (ISSNHL) during the initial stage of treatment were examined in 51 patients who
      showed significant recovery. By plotting average hearing threshold level or
      degree of average hearing improvement against number of days after the first
      examination, a pattern of recovery was seen for each patient, and the
      superimposed patterns of hearing recovery were examined as a whole and in groups.
      The results indicated that most patients showed either initial rapid recovery
      reaching a plateau or a very gradual and slow recovery. In a small number of
      patients, the pattern of rapid recovery appeared somewhat delayed. Further
      analysis by grouping the patients revealed that initial rapid recovery was
      frequently observed in the groups which showed smaller degree of hearing loss at
      the first examination, greater degree of hearing improvement overall, and smaller
      degree of hearing loss once stable. The results of this study appear to indicate
      that patterns of recovery at the initial stage of ISSNHL reflect the prognosis to
      a certain degree.

PMID- 8985561
TI  - Audiological findings after multichannel cochlear implantation in patients with
      Mondini dysplasia.
AB  - Mondini dysplasia is a congenital malformation of the inner ear. To date, five
      individuals with this malformation have received cochlear implants at the South
      of England Cochlear Implant Centre. The aim of this study was to review the
      audiological findings of these individuals after implantation. The soundfield
      thresholds after implantation are in the region of 30-40 dB (A). The results of
      suprathreshold speech recognition tasks show substantial variability in
      performance but this is no greater than that obtained from implant users with no
      malformation. All individuals were able to detect and recognize a variety of
      environmental sounds that would previously have been inaudible. These findings,
      along with the reported improvement in quality of life, mean that Mondini
      dysplasia is not a contra-indication for multichannel cochlear implantation. This
      information will be useful to other centres when considering implantation in
      similar patients.

PMID- 8985563
TI  - Audit of the distraction test of hearing at about 8 months of age: results of a
      survey of Scottish health boards.
AB  - The distraction test of hearing at 8 months is offered in all Scottish health
      boards and is a recommendation of the Hall Report 'Health for all Children'. As
      part of a Scotland-wide project to assess the feasibility of an audit of pre
      school surveillance programmes using routinely collected data, all boards were
      asked for information about this screening test. The results showed that all
      boards regarded it as a worthwhile screening test in the present circumstances
      for early detection of sensorineural hearing loss (SNHL). The limitations on the
      reliability of the test were recognized by many boards. The quality elements of
      the whole screening process were examined, including screening technique,
      recording of results, provision of equipment and suitable test conditions, and
      staff training. The results showed variations in the attention given to quality
      standards. The results also showed a number of gaps in availability of data on
      coverage, results, and outcomes. Only one board was realistically able to audit
      the distraction test at all stages using routinely collected data. Availability
      of data will improve with the introduction of the national computerized Pre
      school Child Health Surveillance Programme (CHSP) into the majority of health
      boards. The reliability and validity of audit results whether at board level or
      Scotland-wide level will depend on maintenance and adherence to quality standards
      in performing the test, in recording of results and also in ensuring adequate
      coverage.

PMID- 8985562
TI  - Auditory performance and acoustic reflexes in young adults reporting listening
      difficulties.
AB  - We aimed to determine whether reported difficulties in speech understanding are
      associated with abnormal acoustic reflex thresholds (ARTs). The acoustic reflex
      has been shown to have a role in the understanding of speech at high intensities
      by ensuring that the strong low-frequency components of sound do not excessively
      mask the higher-frequency components, which are important for speech
      understanding. There is also wide variance in individual ARTs. Hence, the
      possibility arises that subjects reporting listening difficulties in noise have
      abnormal acoustic reflex function. In this investigation, a questionnaire to 2395
      university students was used to obtain 20 subjects reporting listening
      difficulties in background noise and requesting advice about their hearing
      problems; it also screened out significant histories of middle ear disease in
      childhood. These subjects, and 20 control subjects reporting no listening
      difficulties, received a battery of performance tests and measures of acoustic
      reflex thresholds. Results showed significant differences in auditory performance
      between subjects reporting listening difficulties and those with no such
      difficulties, but no differences in acoustic reflex thresholds. These findings
      extend the relationship between reported listening difficulties and auditory
      performance within the "normal hearing' range, but this relationship is unlikely
      to be due to abnormal acoustic reflex thresholds.

PMID- 8985564
TI  - Hearing complaints of patients with King-Kopetzky syndrome (obscure auditory
      dysfunction).
AB  - The hearing complaints in patients with King-Kopetzky syndrome were studied by
      use of the open-ended hearing problem questionnaire. The main findings are that
      complaints were commonly focused on the categories of 'live speech' and
      'electronic speech' difficulties in patients with King-Kopetzky syndrome,
      particularly the auditory difficulties of speech in noise and group conversation.
      However, they reported problems with warning signals significantly less
      frequently than a control 'audiological rehabilitation' group and the patients
      studied by Barcham and Stephens (1980). In addition, main psychological problems
      were related to anxiety (e.g. irritability, nervousness and moodiness) in
      patients with King-Kopetzky syndrome. The open-ended hearing problem
      questionnaire appears to be a useful tool that can be used to high-light the
      speech hearing disability encountered by patients with King-Kopetzky syndrome.

PMID- 8985565
TI  - Prader-Willi syndrome--a case report of the multidisciplinary management of the
      orofacial problems.
AB  - A 24-year-old man with Prader-Willi syndrome presented with a class III
      malocclusion, featuring maxillary hypoplasia and severe enamel deficiency.
      Treatment involved orthodontic alignment, surgical advancement of the maxilla and
      restorative treatment to augment vertical facial height, improve the final
      occlusion and increase short clinical dental crown heights. The principal
      features of the syndrome and the management of this case are discussed.

PMID- 8985566
TI  - Distal movement without headgear: the use of an upper removable appliance for the
      retraction of upper first molars.
AB  - The potential hazards and patient resistance to wearing extra-oral appliances are
      well documented. A method of distalizing molars without the need for head-gear is
      described.

PMID- 8985567
TI  - Bonded retainers 'hands free'.
AB  - A simple technique is described to position and maintain a wire retained during
      direct bonding using a custom made acrylic carrier.

PMID- 8985568
TI  - Obstructive sleep apnoea: fact not fiction.
AB  - Obstructive sleep apnoea (OSA) is a recognized clinical disorder in which periods
      of cessation of breathing occur in the presence of inspiratory effort. Because
      this may have serious cardio-vascular and pulmonary consequences, diagnosis, and
      adequate treatment are important. Apart from its medical repercussions, OSA
      adversely affects the quality of life of both the sufferer and his family. This
      paper aims to give an overview of the complaint, defining and describing the
      disorder, reporting its signs and symptoms, and discussing its diagnosis and
      treatment. Particular attention will be given to those areas in which the
      orthodontist may play an active role.

PMID- 8985569
TI  - Adhesive pre-coated brackets, a comparative clinical study.
AB  - The adhesive pre-coated bracket system along with the application of light curing
      for orthodontic bracket placement were compared with a conventional adhesive
      system, in a prospective randomized study. Of 38 consecutive patients requiring
      fixed orthodontic appliances, half were treated with adhesive pre-coated brackets
      and half with a no-mix adhesive. The timings for the clinical stages involved in
      bracket placement, were recorded. This also included the time and reliability of
      bracket identification and orientation. The peri-bracket flash distribution, time
      taken for clean up at the subsequent visit, the site, and number of bracket
      failures at the time of bracket placement and during the first 3 months, were
      recorded. The study showed that although the time taken to place and cure the
      adhesive pre-coated system was longer than for the no-mix system, this difference
      was not statistically significant. However, this difference in time was
      compensated for in the time taken for bracket orientation in the control group
      and subsequent clean up at the second visit. Both the bracket failure rate and
      peri-bracket flash scores were reduced in the adhesive pre-coated group as
      compared with the control and these differences were statistically significantly.
      Other advantages of the adhesive pre-coated system are reported.

PMID- 8985570
TI  - Factors influencing the uptake of orthodontic treatment.
AB  - The aim of this investigation was to evaluate the factors that influenced the
      uptake of orthodontic treatment for patients who were referred for orthodontic
      treatment to two types of orthodontic treatment provider; a fee per item and
      hospital service. The following data were collected: (i) basic demographic data;
      (ii) the need for orthodontic treatment as measured by IOTN; and (iii) the
      outcome of the consultation. The data analysis with logistic regression revealed
      that the following variables had a predictive effect on the uptake of treatment:
      (i) the need for orthodontic treatment; and (ii) the patient's gender. Most of
      the patients that were referred and accepted for treatment had a definite need
      for orthodontic treatment.

PMID- 8985571
TI  - Factors associated with the standard and duration of orthodontic treatment.
AB  - The pretreatment and post-treatment study casts and records of 156 completed
      fixed appliance and removable appliance cases were analysed, and the influence of
      various factors on the standard of result, as measured by the change in PAR score
      produced by treatment and the duration of treatment, was assessed. For the
      purpose of analysis the sample was divided into two groups; a two-arch fixed
      appliance group (n = 81) and a removable/mini fixed appliance group (n = 75).
      Multiple regression procedures were carried out separately for both groups,
      first, with all gathered data and, secondly, with only information which would be
      known at the start of treatment. For fixed appliances the initial PAR score was
      consistently an influential variable on change in PAR score and duration of
      treatment. Patient compliance, the need to extract a permanent first molar and
      the presence of an anterior crossbite were also important. The initial PAR score
      also explained much of the variation in change in PAR for removable/mini fixed
      appliances, but generally, regression models for this group were less well
      fitting.

PMID- 8985572
TI  - In vitro measurement of enamel demineralization in the assessment of fluoride
      leaching orthodontic bonding agents.
AB  - The aim of this study was to measure in vitro demineralization around orthodontic
      brackets, bonded with five different bonding agents. Two conventional bonding
      agents, two fluoride-leaching agents, and a glass ionomer were tested. A sixth
      group utilized a fluoride varnish after bonding. The amount of dissolved enamel
      mineral was determined from increases in the phosphorus concentration in the
      demineralizing solution and measurements were made over a 4 week period. The
      results confirmed that when fluoride is present in the form of a fluoride
      leaching bonding agent or a fluoride varnish, resistance to demineralization is
      enhanced. Analysis of variance showed that Ketac-cem, Concise with Duraphat, and
      Pulpdent O.B.A. performed statistically significantly better than Concise, Bond
      fast, and Rely-a-bond, in resisting enamel demineralization.

PMID- 8985573
TI  - Practical application of the PAR index: an illustrative comparison of the outcome
      of treatment using two fixed appliance techniques.
AB  - A retrospective assessment of treatment outcome in a group of 82 orthodontic
      fixed appliance cases was carried out using the Peer Assessment Rating Index
      (PAR) in order to explore the usefulness of the PAR index as a means of
      differentiating the change associated with treatment. Two different fixed
      appliance techniques, the pre-adjusted Edgewise and the Begg appliance had been
      used to treat these cases, and all had been under the care of one Consultant
      Orthodontist. The mean percentage reduction in PAR for the group as a whole was
      74 per cent. Comparison of the two different appliance types found that the pre
      adjusted Edgewise group achieved a significantly greater reduction in PAR score
      (81 per cent), than the Begg group (65 per cent). Cases with a low PAR score
      prior to treatment tended to fare more poorly in terms of percentage reduction
      and this was more marked for those cases treated with the Begg appliance.
      Although the PAR index has a high degree of reproducibility, it was found that
      even the small error present can lead to problems of interpretation if the
      nomogram categories are used as a method of comparison. Some potential problems
      in undertaking studies such as this using the PAR index to assess treatment
      outcome are discussed.

PMID- 8985574
TI  - Orthodontic treatment planning by general dental practitioners.
AB  - A group of 30 general dental practitioners were asked to plan treatment for a
      series of 10 Class II division 1 malocclusions of graded severity. The results
      were assessed against a gold standard provided by three consultants. Only 14 per
      cent of practitioner treatment plans agreed with the gold standard and agreement
      was worst for those cases requiring the use of headgear. When consultants and
      General Dental Practitioners (GDPs) were asked whether a case should be referred
      for advice before the GDP began treatment, 64 per cent of GDP decisions agreed
      with those of the consultants. On 13 per cent of occasions, however, the GDP
      would have initiated incorrect treatment without seeking consultant advice.

PMID- 8985575
TI  - Orthodontic auxiliaries.

PMID- 8985576
TI  - Transition from NHS to private practice.
AB  - This article describes the process of change in a specialist orthodontic practice
      from NHS to private, the development of a business plan and its subsequent
      implementation. The very nature of change is variability and the unique
      personality of an orthodontic practitioner and the make-up of the regional
      orthodontic environment mean that this article cannot provide a definitive guide
      to change. However, the general principles are applicable to changes in most
      circumstances and are illustrated with reference to the author's own practice.

PMID- 8985577
TI  - Simplifying orthodontic analysis.

PMID- 8985578
TI  - The effects of extracting upper second permanent molars.

PMID- 8985579
TI  - Seeking justice for Priscilla.

PMID- 8985580
TI  - Recapturing justice in the managed care era.

PMID- 8985581
TI  - Caring for "socially undesirable" patients.

PMID- 8985582
TI  - Justice and the individual in the Hippocratic tradition.

PMID- 8985583
TI  - The eclipse of the individual in policy (where is the place for justice?)

PMID- 8985584
TI  - Allocating healthcare by QALYs: the relevance of age.

PMID- 8985585
TI  - The economic attributes of medical care: implications for rationing choices in
      the United States and United Kingdom.

PMID- 8985586
TI  - Justice, society, physicians and ethics committees: incorporating ideas of
      justice into patient care decisions.

PMID- 8985587
TI  - The ethical neutrality of prospective payments: justice issues.

PMID- 8985588
TI  - Rebecca Reichmann on womens' health and reproductive rights in Brazil. Interview
      by Steve Heilig.

PMID- 8985590
TI  - Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a
      new member of the S100 gene cluster on chromosome 1q21.
AB  - Here, we report the characterization of a human cDNA coding for the recently
      published amino acid sequence of a calcium-binding S100 protein, S100A12 (CGRP,
      calgranulin C, CAAF1, p6). The exon/intron structure of the S100A12 gene is
      similar to most other S100 genes. It is composed of three exons which are divided
      by two introns of 900 bp and 400 bp. The protein is encoded by sequences in exons
      2 and 3, with exon 2 coding for the N-terminal 45 amino acids and exon 3 coding
      for the C-terminal 46 amino acids. So far, ten S100 genes are known to be located
      on human chromosome 1q21 in a clustered organization. Hence, we investigated
      whether S100A11 (S100C, calgizzarin) and S100A12 are also localized in the S100
      gene cluster. We found both genes within the cluster, with S100A11 being close to
      S100A10 and S100A12 between the genes S100A8 and S100A9. Therefore, the S100 gene
      cluster now is composed of 12 differentially expressed family members.

PMID- 8985589
TI  - Redox modulation of calcium entry and release of intracellular calcium by
      thimerosal in GH4C1 pituitary cells.
AB  - In the present work we have investigated the actions of the oxidizing sulfhydryl
      reagent thimerosal on different mechanisms which regulate intracellular free Ca2+
      concentration ([Ca2+]i) in GH4C1 pituitary cells. In intact Fura-2 loaded cells,
      low concentrations of thimerosal potentiated the spike phase of the TRH-induced
      (thyrotropin-releasing hormone) rise in [Ca2+]i, whereas high thimerosal
      concentrations inhibited it. The effect of thimerosal on the plateau phase was
      always inhibitory. The effect of thimerosal on the IP3-induced calcium release
      (IICR) was studied in permeabilized cells using the Ca2+ indicator Fluo-3. A low
      concentration of thimerosal (10 microM) stimulated IICR: the Ca2+ release induced
      by 300 nM inositol-1,4,5-trisphosphate (IP3) was enhanced in cells treated with
      thimerosal for 1 or 6 min (67 +/- 11 nM and 34 +/- 5 nM, respectively) as
      compared to control cells (17 +/- 2 nM). On the other hand, a high concentration
      of thimerosal (100 microM) inhibited IICR: when IP3 (10 microM) was added after a
      5 min preincubation with thimerosal, the IP3-induced rise in [Ca2+]i (46 +/- 14
      nM) was 57% smaller as compared with that seen in control cells (106 +/- 10 nM).
      The effect of thimerosal on the voltage-operated Ca2+ channels (VOCCs) was
      studied by depolarizing intact Fura-2 loaded cells by addition of 20 mM K+ to the
      cuvette. The depolarization-evoked increase in [Ca2+]i was inhibited in a dose
      dependent manner by thimerosal. Direct evidence for an inhibitory effect of
      thimerosal on VOCCs was obtained by using the whole-cell configuration of the
      patch-clamp technique: thimerosal (100 microM) potently inhibited the Ba2+
      currents through VOCCs. In addition, our results indicated that thimerosal
      inhibited the caffeine-induced increase in [Ca2+]i, and activated a capacitative
      Ca2+ entry pathway. The actions of thimerosal were apparently due to its
      oxidizing activity because the effects were mostly reversed by the thiol-reducing
      agent dithiothreitol (DTT). We conclude that, in GH4C1 pituitary cells, the
      mobilization of intracellular calcium and the different Ca2+ entry pathways are
      sensitive to redox modulation.

PMID- 8985591
TI  - Time-resolved fluorescence of S-100a protein: effect of Ca2+, Mg2+ and
      unilamellar vesicles of egg phosphatidylcholine.
AB  - Phase-modulation fluorescence lifetime measurements were used to study the single
      Trp residue of the Ca(2+)-binding protein S-100a both in the absence and in the
      presence of Ca2+ and/or Mg2+. Trp fluorescence decay for the protein was
      satisfactorily described by Lorentzian lifetime distributions centered around two
      components (approximately 4 ns and 0.5 ns). Lifetime values were unchanged by 2
      mM Ca2+, but the fractional intensity associated with longer lifetime increased
      up to 75%. In the presence of Mg2+, the Ca2+ induced increase of the fractional
      intensity associated with longer lifetime was only 57%. For the protein in
      buffer, about the 85% of the recovered anisotropy was associated to a rotational
      correlation time of 6.7 ns. After the addition of Ca2+, this value was increased
      to 16.08 ns. In the presence of Mg2+, Ca+2 increased the rotational correlation
      time to 33.75 ns. Similar studies were performed with S-100a interacting with egg
      phosphatidylcholine vesicles (SUV). Our data suggest that the conformation of the
      protein may be influenced by structural features of the lipidic membrane.
      Moreover, data obtained in the presence of Mg2+ indicate some interaction between
      lipids and S-100, likely mediated by this ion.

PMID- 8985592
TI  - Temperature modulates the Ca2+ current of HIT-T15 and mouse pancreatic beta
      cells.
AB  - The effects of raising temperature on the Ca2+ currents of insulin-secreting HIT
      and mouse pancreatic beta-cells were studied. Currents were measured in 3 mM Ca2+
      containing solutions using standard whole-cell techniques. Increasing temperature
      from 22 degrees C to 35 degrees C increased peak Ca2+ current amplitude, percent
      (fast) inactivation and decreased the time-to-peak of the current. Ca2+ currents
      in HIT and mouse beta-cells responded in the same manner to an imposed
      physiological burstwave with test-pulses: (i) application of the burstwave
      inactivated the test-pulse Ca2+ current at both high and low temperatures; (ii)
      Ca2+ current inactivation leveled off during the plateau phase at 20-22 degrees C
      whereas there was an apparent continual decay at 33-35 degrees C; and (iii)
      recovery from inactivation occurred during the interburst period at both
      temperatures. Application of a physiological burstwave without test-pulses to
      mouse beta-cells before and after addition of 0.2 mM Cd2+ resulted in a Ca2+
      difference current. This current activated during the hyperpolarized interburst
      phase, activated, inactivated and deactivated rapidly and continually during the
      plateau phase, and recovered from inactivation during the interburst. Although
      raising temperature strongly modified HIT and mouse beta-cells Ca2+ current, our
      work suggests that other channels, in addition to Ca2+ channels, are likely to be
      involved in the control of islet bursts, particularly at different temperatures.
      In addition, the effect of temperature on islet cell Ca2+ current may be partly
      responsible for the well-known temperature dependence of glucose-dependent
      secretion.

PMID- 8985593
TI  - The amount of acetylcholine mobilisable Ca2+ in single smooth muscle cells
      measured with the exogenous cytoplasmic Ca2+ buffer, Indo-1.
AB  - Single smooth muscle cells from guinea pig urinary bladder were voltage clamped
      with patch electrodes containing 1 mM Indo-1. As Indo-1 entered the cell,
      delta[Ca2+]i in response to Ca2+ influx with ICa (1 s steps to -10 mV) was
      progressively decreased. delta F410 was used as a measure of the Ca2+ amount
      bound to Indo-1. Within less than 2 min after establishment of the whole-cell
      configuration, the fraction of Ca2+ entering the cell with ICa which binds to
      Indo-1 became constant, suggesting that Indo-1 completely overrides the
      endogenous Ca2+ buffers. Under these conditions, delta F410 was satisfactorily
      fitted with the time integral of ICa during 1 s long steps. Acetylcholine (ACh,
      50 microM) was rapidly applied to Indo-1 loaded cells to induce IP3-induced Ca2+
      release (IICR), which peaked within about 1 s. From delta F410 in response to ICa
      and ACh and from the time integral of ICa the amount of Ca2+ released during IICR
      was estimated to be 680 attomole (680 x 10(-18) mole), corresponding to 230
      microM for 3 pl of accessible cytoplasmic volume.

PMID- 8985594
TI  - The autoantigen La/SSB is a calmodulin-binding protein.
AB  - The work reported here has been directed to the identification of new nuclear
      calmodulin-binding proteins. To achieve this goal, nuclei from rat hepatocytes
      were purified and a fraction enriched in DNA- and RNA-binding proteins was
      extracted using DNase I and RNase A. Calmodulin-binding proteins present in this
      nuclear subfraction were purified by chromatography using first a DEAE-Sephacel
      column and subsequently a calmodulin-Sepharose column. Four major polypeptides of
      118, 107, 48 and 45 kDa were found to bind to the calmodulin column in a Ca(2+)
      dependent way. [125I]-calmodulin overlay analysis confirmed that the proteins of
      118, 48 and 45 kDa are calmodulin-binding proteins. These proteins bind single
      stranded and also double-stranded DNA. A partial amino acid sequence obtained
      from the 48 kDa protein revealed a 100% identity with the La/SSB protein, an
      autoantigen implicated in several autoimmune diseases, such as lupus
      erythematosus and Sjogren's syndrome. Two-dimensional gel electrophoresis,
      Western blot analysis and experiments of binding to poly(U), also supports the
      identity of p48 as La/SSB. CaM and La/SSB protein colocalize in the
      heterochromatinic regions within the nucleus of rat hepatocytes. Preincubation of
      La/SSB with calmodulin in the presence of Ca2+ resulted in an increase in the
      binding of ssDNA to La/SSB, suggesting that calmodulin can play a role in the
      regulation of the association of La/SSB with DNA.

PMID- 8985595
TI  - SK&F 96365 inhibits intracellular Ca2+ pumps and raises cytosolic Ca2+
      concentration without production of nitric oxide and von Willebrand factor.
AB  - The effects of the imidazole compound SK&F 96365 on Ca2+ movements and production
      of nitric oxide (NO) and von Willebrand factor (vWF) have been investigated in
      human endothelial cells. Changes in cytosolic Ca2+ concentration ([Ca2+]i) were
      measured with Fura-2. Real-time production of NO was monitored with a porphyrinic
      microsensor and the release of vWF with an enzyme-linked immunosorbent assay.
      Irrespective of the transmembrane Ca2+ gradient, 30 microM SK&F 96365 doubled
      [Ca2+]i suggesting a Ca2+ release from intracellular stores. The SK&F 96365
      induced [Ca2+]i rise was not accompanied by detectable NO and vWF production,
      while 1 microM thapsigargin enhanced [Ca2+]i 2.5 times, doubled the secretion of
      vWF and increased the NO production to 10 +/- 4 nM (n = 5). Pretreatment with
      SK&F 96365 prevented thapsigargin from increasing [Ca2+]i, NO production and vWF
      secretion. To investigate the mechanism by which SK&F 96365 released Ca2+ from
      internal pools, its effect and that of thapsigargin on the ATP-dependent 45Ca2+
      uptake into platelet membrane vesicles were compared. SK&F 96365 as thapsigargin,
      dose-dependently reduced the initial rate of 45Ca2+ uptake. In conclusion, we
      demonstrate that, in the absence of Ca2+ entry from the extracellular space, the
      [Ca2+]i increase elicited by SK&F 96365 or thapsigargin is not sufficient to
      initiate NO synthesis and vWF secretion. This confirms the important role of Ca2+
      influx in endothelial secretion processes.

PMID- 8985596
TI  - Intracellular chelation of calcium prevents cell damage following severe hypoxia
      in the rat cerebral cortex as studied by NMR spectroscopy ex vivo.
AB  - Nuclear magnetic resonance (NMR) spectroscopy was used to quantify metabolic
      recovery (by 31P NMR) and neuronal damage (by 1H NMR) following aglycaemic
      hypoxia in superfused cortical brain slices. Slices were incubated either in the
      absence or presence of a cell-permeant Ca2+ chelator, 1,2-bis-(2-amino
      phenoxy)ethane-N,N,N',N'-tetra-acetic acid acetoxy ester (BAPTA-AM) before
      exposure to hypoxia in the presence or absence of 1.2 mM Ca2+. Hypoxia in the
      presence of Ca2+ resulted in metabolic damage as well as time-dependent reduction
      of a neuronal metabolite, N-acetyl aspartate. The recovery was improved only
      temporarily by BAPTA under these conditions. Hypoxia in the absence of external
      Ca2+ did not cause any detectable signs of damage in BAPTA-loaded slices. These
      data show that combined inhibition of influx and intracellular chelation of Ca2+
      render the brain cortex tolerable to severe energy failure.

PMID- 8985597
TI  - Involvement of mitochondria in intracellular calcium sequestration by rat
      gonadotropes.
AB  - Intracellular Ca2+ ([Ca2+]i) dynamics were studied in identified rat gonadotropes
      using the whole-cell patch-clamp technique in conjunction with Indo-1 photometry.
      The kinetics of depolarization-induced [Ca2+]i transients vary with Ca2+ load. In
      addition to a rapid initial decay, large (> 500 nM) [Ca2+]i transients have a
      slow plateau phase. Application of the mitochondrial inhibitor carbonyl cyanide m
      chlorophenylhydrazone (CCCP) significantly slows the decay of [Ca2+]i transients,
      consistent with stopping uptake of Ca2+ by mitochondria. CCCP causes a small
      increase of [Ca2+]i at rest. After a large Ca2+ entry the amount is much larger,
      consistent with release from a mitochondrial Ca2+ pool that fills during
      cytoplasmic Ca2+ loading. The rate of Ca2+ uptake by mitochondria is dependent
      upon [Ca2+]i. Consistent with previous studies, gonadotropin releasing hormone
      (GnRH) induces [Ca2+]i oscillations. The mitochondrial inhibitors CCCP and
      cyanide (CN-) terminate these oscillations. The mitochondrial ATP-synthase
      inhibitor oligomycin reduces the frequency and increases the amplitude of the
      oscillations. In the presence of ruthenium red (a non-specific blocker of the
      mitochondrial Ca(2+)-uniporter) in the pipette, GnRH does not induce rhythmic
      [Ca2+]i oscillations. We suggest that mitochondria play a significant role in the
      rapid clearance of cytosolic Ca2+ loads in gonadotropes and participate in GnRH
      induced periodic [Ca2+]i oscillations.

PMID- 8985598
TI  - Effects of panel experience on olfactory memory performance: influence of stimuli
      familiarity and labeling ability of subjects.
AB  - This work attempted to define the impact of panel experience on olfactory memory
      performance by comparing scores in an odor recognition task obtained from a
      highly trained descriptive panel (17 subjects) and a naive one (33 subjects with
      no experience in sensory analysis). During the inspection phase, 16 odorants were
      presented monadically to subjects for familiarity rating and a written
      description. The recognition session was planned 7 days later with 32 odorants
      (including the 16 of the target set). Subjects also described the odor of the
      stimuli. The memory performance of each panel was estimated by the mean value of
      individual d' (index of detectability). Training of the descriptive panel did not
      enhance the olfactory memory ability, which strengthened the well-established
      idea that odor memory is closely linked to personal experience of the subject
      with the stimuli. However, odor recognition performances were improved by a
      precise and consistent answer at the encoding task: for both groups, subjects
      performed better when stimuli were precisely labeled and consistently used.
      Trained subjects were more accurate when describing than naive ones, whatever the
      degree of familiarity. Panel experience allowed trained subjects to verbalize
      their perception especially accurately when stimuli were familiar.

PMID- 8985599
TI  - Pemenone and androstenone do not cross-adapt reciprocally.
AB  - Explorations of the qualitative and quantitative differences between the odors of
      pemenone (PEM), androstenone (AND) and isovaleric acid (IVA) show that they share
      a number of common perceptual characteristics. Among these are similarities in
      their odor quality and relative intensity ratings. PEM is also an efficient cross
      adaptor and modulator of a subject's AND sensitivity. Here we evaluate the
      reciprocal efficacy of AND adaptation to alter the perceived intensity and
      quality of PEM, IVA and AND. Twenty-three people, including both those osmic and
      allosmic (n = 11) for the putrid odor quality of PEM, were tested. Following
      training in odor quality and intensity rating techniques, subjects sampled a
      selected substance for 2 min to obtain adaptation and then reported quality and
      intensity ratings for the three test stimuli. There was significant self
      adaptation by PEM and IVA in all subjects, but self-adaptation by AND was only
      observed in the PEM-osmic subjects. AND did not cross-adapt PEM or IVA to any
      significant extent. Collectively, these results contrast with our earlier study
      in which PEM was an efficient cross-adaptor of AND. Here, AND was no more
      efficient than the control as an adapting substance for PEM, despite significant
      self-adaptation of PEM by itself. This lack of reciprocity in the effectiveness
      of PEM and AND as cross-adapters is not related to differences in odor intensity,
      as the PEM and AND concentrations were adjusted for each subject to elicit
      comparable intensity reports. These results support the notion that PEM, AND and
      IVA share certain perceptual characteristics, but interact differentially with
      three or more sets of perceptual channels that are now thought to result in a
      putrid odor quality.

PMID- 8985600
TI  - Are odorant-binding proteins involved in odorant discrimination?
AB  - Pheromone-sensitive sensilla trichodea of nine moth species belonging to six
      families and three superfamilies of Lepidoptera were immunolabelled with an
      antiserum against the pheromone-binding protein of Antheraea polyphemus. Strong
      immunolabelling of the sensillum lymph was observed in all long sensilla
      trichodea of A. polyphemus, A. pernyi (Saturniidae), Bombyx mori (Bombycidae) and
      Manduca sexta (Sphingidae). Very weak labelling was found with all sensilla
      trichodea of Dendrolimus kikuchii (Lasiocampidae) and Lymantria dispar
      (Lymantriidae). In three noctuid species, some long sensilla trichodea were
      labelled strongly, some only weakly and some were not labelled at all. The
      fraction of long sensilla trichodea that were strongly labelled was large in
      Helicoverpa armigera, but small in Spodoptera littoralis and Autographa gamma.
      The observed cross-reactivity was not correlated with taxonomic relatedness of
      the species but rather with chemical relatedness of the pheromones used by these
      species, as a high labelling density was consistently observed in sensilla tuned
      to pheromones with an alcyl chain of 16 carbon atoms. The highly divergent
      specificity of pheromone-receptor cells in Noctuidae appears to be mirrored by a
      similar diversity of the pheromone-binding proteins in the sensilla trichodea.
      These data support the notion that pheromone-binding proteins participate in
      odorant discrimination.

PMID- 8985601
TI  - Electrophysiological and morphological properties of neurons acutely isolated
      from the rostral gustatory zone of the rat nucleus of the solitary tract.
AB  - The biophysical and morphological characteristics of acutely isolated neurons
      from the rostral nucleus of the solitary tract (rNST) were investigated under
      current clamp conditions and compared with the results obtained from neurons
      recorded in brain slices. The passive membrane properties of the isolated neurons
      were similar to rNST neurons in brain slices and the neurons maintained their
      morphological characteristics although their dendritic tree was truncated. The
      isolated neurons also retained their characteristic repetitive firing properties.
      In addition we also noted developmental changes in the intrinsic membrane
      properties of the isolated neurons, such as a shortening in action potential
      duration, decrease in membrane time constant and input resistance, that occurred
      when these parameters were compared in neurons isolated from young (5-10 days)
      and older animals. These enzymatically dispersed neurons therefore retained both
      the membrane properties and morphology observed in the intact brainstem and in
      vitro brain slice preparation. The use of this isolated neuron preparation
      provides a basis for further study of rNST neurobiology.

PMID- 8985602
TI  - Vasopressin modulates membrane properties of taste cells isolated from bullfrogs.
AB  - The effect of arginine vasopressin (AVP) on the membrane properties was analyzed
      in isolated bullfrog taste cells using a perforated whole-cell patch-clamp
      technique. AVP (100 nM) induced three kinds of responses in rod-type taste cells:
      appearance of inward current, inhibition of voltage ramp-induced outward current
      and enhancement of the outward current. The Ca(2+)-ionophore ionomycin (3 microM)
      also induced inward current in taste cells. A membrane-permeable cAMP analog, 8
      CPT-cAMP (0.3 mM) inhibited voltage ramp-induced outward current in some rod
      cells, but enhanced the current in other rod cells. The results suggest that AVP
      may increase either intracellular Ca2+ level or cAMP level in taste cells,
      modulating the membrane excitability.

PMID- 8985603
TI  - Evolution of the sweetness receptor in primates. II. Gustatory responses of non
      human primates to nine compounds known to be sweet in man.
AB  - The gustatory responses of nine compounds, namely glycine, D-phenylalanine, D
      tryptophan, cyanosuosan, magapame, sucrononate, campame, cyclamate and
      superaspartame, all known as sweet in man, were studied in 41 species or
      subspecies of non-human primates, selected among Prosimii (Lemuridae and
      Lorisidae), Platyrrhini (Callitrichidae and Cebidae) and Catarrhini
      (Cercopithecidae, Hylobatidae and Pongidae). The first six compounds are
      generally sweet to all primates, which implies that they interact with the
      primate sweetness receptors essentially through constant recognition sites.
      Campame is sweet only to Cebidae and Catarrhini, cyclamate only to Catarrhini,
      superaspartame principally to Callitrichidae and Catarrhini, which implies that
      all these compounds interact with the receptors partly through variable
      recognition sites. From the present work, from other previous results (where
      notably it was observed that alitame is sweet to all primates, ampame only to
      Prosimii and Catarrhini, and aspartame only to Catarrhini), and from the
      multipoint attachment (MPA) theory of sweetness reception (as elaborated by Nofre
      and Tinti from a detailed study of structure-activity relationships of various
      sweeteners in man), it is inferred that the primate sweetness receptors are very
      likely made up of eight recognition sites, of which the first, second, third,
      fourth, seventh and eighth are constant, and the fifth and sixth variable. From
      these results and from the MPA theory, it is also inferred that the recognition
      sites of the primate sweetness receptors could be: Asp-1 or Glu-1, Lys-2, Asp-3
      or Glu-3, Thr-4, X-5, X-6, Thr-7, Ser-8, where the variable recognition sites X-5
      and X-6 would be: Ala-5 and Ala-6 for Callitrichidae, Ser-5 and Ala-6 for
      Cebidae, Ala-5 and Thr-6 for Prosimii, and Thr-5 and Thr-6 for Catarrhini. By
      using Tupaiidae (tree shrews) as a reference outgroup and by means of other
      structural and functional molecular considerations, it appears that
      Callitrichidae have retained the most primitive receptor among the four types of
      primate receptors. The possible taxonomic and phylogenetic implications of these
      findings are discussed.

PMID- 8985604
TI  - Difference in behavior between responses to forskolin and general odorants in
      turtle vomeronasal organ.
AB  - To elucidate the signal transduction mechanisms in the turtle vomeronasal
      receptor neurons, the effects of forskolin, changes in mucosal Ca2+
      concentrations and ruthenium red on the responses of the accessory olfactory bulb
      to general odorants were examined. Forskolin elicited a large response,
      suggesting that there are cAMP-gated channels in the vomeronasal neurons. On the
      other hand, the dependence of the responses to general odorants on Ca2+
      concentrations was different from that of the response to forskolin. A large
      response to an odorant (n-amyl acetate) appeared after the cAMP-mediated pathway
      was fully desensitized by application of 50 microM forskolin. These results
      suggest that the cAMP-mediated pathway does not contribute significantly to
      generation of the response to general odorants. A concentration of 50 microM
      ruthenium red significantly reduced the responses to n-amyl acetate alone and
      after 50 microM forskolin desensitization, suggesting that the inositol
      triphosphate-mediated pathway contributes partly to generation of the responses
      to general odorants in the vomeronasal neurons.

PMID- 8985605
TI  - A spectroscopic mechanism for primary olfactory reception.
AB  - A novel theory of primary olfactory reception is described. It proposes that
      olfactory receptors respond not to the shape of the molecules but to their
      vibrations. It differs from previous vibrational theories (Dyson, Wright) in
      providing a detailed and plausible mechanism for biological transduction of
      molecular vibrations: inelastic electron tunnelling. Elements of the tunnelling
      spectroscope are identified in putative olfactory receptors and their associated
      G-protein. Means of calculating electron tunnelling spectra of odorant molecules
      are described. Several examples are given of correlations between tunnelling
      spectrum and odour in structurally unrelated molecules. As predicted, molecules
      of very similar shape but differing in vibrations smell different. The most
      striking instance is that of pure acetophenone and its fully deuterated analogue
      acetophenone-d8, which smell different despite being identical in structure. This
      fact cannot, it seems, be explained by structure-based theories of odour. The
      evidence presented here suggests instead that olfaction, like colour vision and
      hearing, is a spectral sense.

PMID- 8985606
TI  - Impact of childhood abuse history on psychological symptoms among male and female
      soldiers in the U.S. Army.
AB  - The long-term psychological effects of four different types of childhood
      maltreatment were examined among 1,072 male and 305 female soldiers on active
      duty in the United States Army. The predictor variables included four subscales
      from the Childhood Trauma Questionnaire (CTQ)-(1) physical-emotional abuse, (2)
      sexual abuse, (3) emotional neglect, and (4) physical neglect. An additional
      sexual abuse variable based on the four screening questions developed by
      Finkelhor, Hotaling, Lewis, and Smith (1990) was also included. Outcome was
      measured by the Brief Symptom Inventory and a dissociation scale developed by
      Briere and Runtz (1988). MANOVAs were conducted for each outcome measure.
      Physical-emotional abuse contributed to most of the effects. However, sexual
      abuse contributed additional significant effects to all of the subscales. In
      general, males and females showed similar outcomes, but certain gender
      differences were noted.

PMID- 8985607
TI  - The socioemotional development of orphans in orphanages and traditional foster
      care in Iraqi Kurdistan.
AB  - In order to investigate orphans' situation and development in Iraqi Kurdistan,
      samples from the two available orphan care systems, the traditional foster care
      and the modern orphanages, are examined at an index test and at 1-year follow-up
      regarding competency scores and behavioral problems at both test occasions, and
      post-traumatic stress reactions at a 1-year follow-up. Achenbach Child Behavior
      Check List (CBCL) and two instruments regarding post-traumatic stress disorder
      (PTSD) were used. While competency scores showed an improvement in both samples
      at the follow-up test, the problem scores increased in the orphanage sample and
      decreased among the foster care subjects. Moreover, the orphanage sample reported
      higher frequency of post-traumatic stress disorder (PTSD) than the foster care
      children. The results are discussed with regard to the value of the Kurdish
      society's own traditions in taking care of orphans.

PMID- 8985608
TI  - Absence of males in maltreatment research: a survey of recent literature.
AB  - This paper provides a review of research in the area of physical maltreatment
      with respect to the degree to which males are represented in research samples.
      The systematic, comprehensive review includes 126 articles published between the
      years 1989 and 1994 in nine primary journals. Results show that adult males are
      dramatically underrepresented in this research. Specifically, males were included
      in fewer than one-half (47.7%) of the 77 articles reviewed and the total number
      and percentage of males in research samples was significantly less than the
      number and percentage of females. Only three studies included males exclusively,
      yet 40 studies involved solely female participants. Of the studies that did
      include men, only 37.5% provided an evaluation of gender differences. Research
      involving abused children showed a much greater representation of male subjects
      than research with adult participants. Only four of 49 studies of abused children
      were based exclusively on girls; a full 62.8% included an equal representation of
      boys and girls.

PMID- 8985609
TI  - Parental substance abuse as a predictor of child maltreatment re-reports.
AB  - This longitudinal study of child abuse and neglect cases closed after
      investigation examined the impact of parental substance abuse on family
      functioning and on subsequent referrals to child protective services. The
      findings support the hypothesis that parental substance abuse would have a
      negative impact on family functioning, which, in turn, would result in a higher
      rate of re-reports. As expected, substance abuse also had a direct impact on re
      reports. It is critical that the child welfare system recognize and respond to
      parental substance abuse problems in these families through expanded and improved
      voluntary, and perhaps, mandatory services.

PMID- 8985610
TI  - Parental abusive versus supportive behaviors and their relation to hostility and
      aggression in young adults.
AB  - The relation of parental support to abuse has rarely been considered in research
      on the sequelae of childhood abuse in adulthood. In this study, using the
      Exposure to Abusive and Supportive Environments Parenting Inventory (EASE-PI),
      young adults who reported higher emotionally abusive parenting (EA) consistently
      reported significantly lower love and support from both parents. The relation
      between physically abusive parenting (PA) and love/support depended upon gender
      of parent and child. EA was significantly related to higher hostility and higher
      aggression, as measured by the Buss-Durkee Hostility Inventory, for both men and
      women, and to reports of physical fights within the family, for women only. PA
      was significantly related to higher aggression but not higher hostility. Lower
      support by fathers, but not by mothers, was significantly related to higher
      hostility. However, lower support of daughters by mothers was significantly
      related to increased physical fights in the family. Results indicate that less
      severe abusive behaviors, especially EA, may have detrimental outcomes of
      hostility and aggression and that supportive behaviors by both mothers and
      fathers may be important factors in the outcome.

PMID- 8985611
TI  - Child abuse in Hong Kong revisited after 15 years: characteristics of victims and
      abusers.
AB  - The purpose of this paper was to examine the characteristics of the victims and
      abusers of child abuse cases on the Child Protection Registry in Hong Kong as of
      March 1995 and to compare findings with a similar community report of child abuse
      in Hong Kong conducted approximately 15 years earlier. As of March 31, 1995,
      there were 457 active cases of child abuse or suspected child abuse (44% male and
      56% female) on the computerized Child Protection Registry. Fifty percent of the
      victims were grade school age children between 7-12, and 62.4% suffered physical
      abuse. The abusers or suspected abusers were 52% male and 48% female with nearly
      half (49%) in their thirties. The majority of abusers were married/cohabiting
      (75%) with only a grade school education (60%). As compared to 1979, there was an
      increase of sexual child abuse cases, female victims of child abuse, and an
      increase in male abusers or suspected abusers.

PMID- 8985612
TI  - Gender-specific outcomes for sexually abused adolescents.
AB  - This study examined the gender differences in outcomes related to school
      performance, suicidal involvement, disordered eating behaviors, sexual risk
      taking, substance use, and delinquent behaviors of male (n = 370) and female
      teenagers (n = 2,681) who self-reported a history of sexual abuse. It was found
      that female adolescents, by and large, engaged in internalizing behaviors and
      males in externalizing behaviors. Male adolescents were found to be at higher
      risk than females in poor school performance, delinquent activities, and sexual
      risk taking. Female adolescents, on the other hand, showed higher risk for
      suicidal ideation and behavior as well as disordered eating. Females showed more
      frequent use of alcohol. However, male adolescents exhibited more extreme use of
      alcohol and more frequent and extreme use of marijuana. Among index female
      adolescents, protective factors against adverse correlates included a higher
      emotional attachment to family, being religious or spiritual, presence of both
      parents at home, and a perception of overall health. Factors that augmented
      adverse correlates for them included a stressful school environment due to
      perceived high levels of substance use in and around school, worry of sexual
      abuse, maternal alcohol consumption, and physical abuse. For male adolescents,
      maternal education and parental concern appeared to be protective factors.

PMID- 8985613
TI  - Cycle of abuse and psychopathology in cleric and noncleric molesters of children
      and adolescents.
AB  - Sexual abuse in childhood is frequently reported among sex offenders and has been
      hypothesized to be one of a number of psychological factors etiologically related
      to perpetration of child molestation in adulthood. In the current study we
      examine a sample of cleric and noncleric admitted child molesters and normal
      control subjects in their exposure to sexual abuse in childhood and current
      psychopathology. Odds ratios for the association between exposure to sexual abuse
      and child molestation were obtained while adjusting for group differences in
      demographic and psychological characteristics. Results indicated exposure to
      sexual abuse in childhood was associated with becoming a child molester for both
      cleric and noncleric offenders (p < .0002). Nonclerics indicated more severe
      psychopathology than clerics. Sexual abuse in childhood is one of many risk
      factors for becoming a perpetrator of child molestation in adulthood for both
      cleric and noncleric child molesters. Noncleric offenders demonstrated more
      sociopathy and mental disorder in general while cleric offenders indicated more
      sexual conflictedness, suggesting different psychoetiologies of offending among
      cleric and noncleric child molesters.

PMID- 8985614
TI  - Persistence of pediatric post traumatic stress disorder after 2 years.
AB  - One-hundred and fifty-six children were randomly evaluated at an inner-city
      juvenile/family court. These children were removed from their parent's custody
      subsequent to a finding of severe child maltreatment. From our original sample of
      156 children, 62 met strict criteria for Post Traumatic Stress Disorder (PTSD).
      Fifty-two of these 62 were successfully recruited and participated in the 2 year
      re-examination. Each PTSD diagnosis was conferred by the Diagnostic Interview for
      Children and Adolescents (DICA). From our sample of 52 PTSD children re-examined
      after 2 years, 17 (32.7%) retained the full PTSD diagnosis, while 67.3% did not
      meet criteria.

PMID- 8985615
TI  - Interviewing children who may have been traumatized.

PMID- 8985616
TI  - Investigative interviews of alleged sexual abuse victims with and without
      anatomical dolls.
AB  - Verbal and nonverbal responses by alleged victims of child sexual abuse were
      coded for length, amount of information, and the manner in which they were
      elicited by the interviewer. In 16 of the interviews, anatomical dolls were
      employed for the purposes of demonstration, whereas they were not used in another
      eight cases matched with respect to other characteristics of the children and the
      alleged events. Children interviewed with dolls provided an equivalent number of
      details and spoke as many words in the substantive portion of the interview as
      did children interviewed without dolls, and interviewers in the two groups used
      similar probes to elicit information. However, the average responses by the
      children were significantly longer and more detailed when dolls were not used.
      Children gave longer and more detailed responses to open-ended invitations when
      dolls were not used. Caution is necessary when interpreting these findings.

PMID- 8985617
TI  - Anatomically-neutral dolls: their effects on the memory and suggestibility of 4-
      to 6-year-old eyewitnesses.
AB  - The purpose of this investigation was to compare the amount and accuracy of
      details provided in the eyewitness accounts of preschool-aged children
      interviewed exclusively with a verbal interview against those interviewed with
      anatomically-neutral dolls in addition to a verbal interview. Forty-four
      children, aged 4 to 6 years, were paired up and assigned as participants or
      observers for an event they engaged in with a confederate. Children's memory was
      assessed afterwards by (a) The Step-Wise Interview (Yuille, Hunter, Joffe, &
      Zaparniuk, 1993); (b) the Step-Wise Interview and big dolls; or (c) The Step-Wise
      Interview and small, detailed dolls and props. Three leading questions were
      incorporated into the interviews. Results indicated no main effect of interview
      type on the overall amount or accuracy of the children's accounts. No main
      effects for interview type or participant versus observer condition were observed
      for the leading questions. Relative to 4-year-olds, 5-year-olds recalled a
      greater number of overall details and were more accurate in their accounts with
      both types of dolls. Females were more accurate than males in their accounts with
      the small detailed toys and props. Implications for the use of anatomically
      neutral dolls in child sexual abuse investigations are discussed.

PMID- 8985618
TI  - Use of corrected QT interval in autonomic function testing: assessment of
      reproducibility.
AB  - QT interval duration is influenced by the autonomic nervous system and has been
      proposed as an additional tool in the diagnosis of diabetic autonomic neuropathy.
      The study aimed to assess in normal subjects the reproducibility of QT interval
      duration compared with that of cardiovascular tests commonly used to explore the
      function of the autonomic nervous system. Fifty-nine healthy subjects (31 males,
      28 females; mean age 35.1 +/- 17.7 years) performed five cardiovascular tests:
      deep breathing test (DBT), lying to standing test (LST), Valsalva manoeuvre (VM),
      postural blood pressure test (PBPT) and cough test (CT). QT interval duration was
      measured on an electrocardiogram (ECG) registered after a 15-min rest in the
      supine position. Corrected QT interval (QTc) was calculated according to Bazett's
      formula. The QTc interval duration for each subject was expressed as the mean of
      the QTc calculated by two observers. Each subject was submitted to the
      cardiovascular test battery and the ECG twice in 1 week. The coefficient of
      variation (CV) was calculated to assess the reproducibility. The observed CV
      values were as follows: DBT 15.8%, LST 8.0%, VM 9.5%, CT 7.2%, PBPT 176%, QTc
      3.4%. Our data confirm the reproducibility of heart rate cardiovascular tests:
      the QTc interval is a reproducible, easily measurable parameter, which has the
      advantage of not requiring patient cooperation.

PMID- 8985619
TI  - The effects of lidocaine on cardiac parasympathetic control in normal subjects
      and in subjects after myocardial infarction.
AB  - It has been widely accepted that lidocaine has little or no effect on the
      autonomic nervous system. However, we have previously shown that in dogs with
      vagally induced atrial fibrillation, lidocaine has a pronounced parasympatholytic
      effect. To study the possible effect of lidocaine on autonomic cardiac control in
      humans, we performed spectral analysis of heart rate fluctuations in 19 healthy
      volunteers, who received an i.v. bolus of lidocaine (1.4 mg/kg), as well as in 13
      patients suffering from acute inferior myocardial infarction (IMI) and 13
      patients suffering from acute anterior myocardial infarction (AMI), who received
      therapeutic doses of i.v. lidocaine infusion (4 mg/min). Heart rate variability
      and respiratory pattern were monitored according to a predetermined protocol,
      with and without lidocaine. Computing the heart rate power spectrum and
      integrating over predetermined frequency bands, we focused mainly on the
      respiratory frequency band, known to predominantly reflect parasympathetic
      control. The administration of lidocaine resulted in a significant overall
      increase in mean heart rate: for the healthy control group an increase of 5.5 +/-
      2.2% (mean +/- SE), for the IMI group an increase of 9.4 +/- 3.5%, and for the
      AMI group an increase of 8.1 +/- 2.9% (p < 0.01 for all). Simultaneously,
      following the administration of lidocaine, there was a decrease in the power of
      respiratory fluctuations: for the healthy control group a decrease of 38.4 +/-
      12.5%, for the IMI group a decrease of 46.3 +/- 32.9%, and for the AMI group a
      decrease of 33.9 +/- 16.2% (p < 0.01 for all). These findings indicate that
      lidocaine has a consistent and significant parasympatholytic effect on the human
      heart, in healthy volunteers as well as in patients in the acute phase of
      myocardial infarction.

PMID- 8985620
TI  - Estimation of fast vagal response by time-dependent analysis of heart rate
      variability in normal subjects.
AB  - In this study, the selective windowed discrete Fourier transform algorithm (SDA)
      for time-frequency analysis was applied on non-stationary heart rate signals,
      recorded during vagal perturbations. These perturbations were achieved in healthy
      subjects (aged 6-42 years) by inducing the oculocardiac reflex and the diving
      response. The results showed that the SDA can detect and quantify the expected,
      although brief, increase in vagal tone, by displaying a marked transient increase
      in the respiratory peak of the time-dependent spectrum. It allowed us to
      demonstrate an age-dependent reduction of the vagal response, obtained from the
      respiratory peak of the heart rate time-dependent spectrum. The SDA approach is
      thus an adequate tool for the evaluation of an instantaneous change in vagal
      activity, as well as steady-state vagal activity, including the detection of a
      malfunction or an exaggerated response of the parasympathetic tone. Since changes
      in heart rate control are expressed by a transient response, they would not have
      been detected by a standard, steady-state spectral analysis of heart rate
      variability, which requires the consideration of long and steady trace lengths
      and would therefore cause smearing of such fast changes. Time-dependent, or
      transient changes in autonomic control can thus be detected and quantified by SDA
      time-frequency analysis.

PMID- 8985621
TI  - Decreased vagal power during treadmill walking in patients with chronic fatigue
      syndrome.
AB  - The purpose of this study was to determine if patients with the chronic fatigue
      syndrome have less vagal power during walking and rest periods following walking,
      in comparison to a group of healthy controls. Eleven patients (ten women and one
      man) who fulfilled the case definition for chronic fatigue syndrome modified to
      reduce heterogeneity and eleven healthy, but sedentary, age- and sex-matched
      controls walked on a treadmill at 2.5 mph four times each for 4 min duration.
      Between each period of walking, subjects were given a 4-min seated rest period.
      Vagal power, a Fourier-based measure of cardiac, parasympathetic activity in the
      frequency range of 0.15 to 1.0 Hz, was computed. In each period of walking and in
      one period of rest, patients had significantly less vagal power than the control
      subjects despite there being no significant group-wise differences in mean heart
      rate, tidal volume, minute volume, respiratory rate, oxygen consumption or total
      spectrum power. Further, patients had a significant decline in resting vagal
      power after periods of walking. These results suggest a subtle abnormality in
      vagal activity to the heart in patients with the chronic fatigue syndrome and may
      explain, in part, their post-exertional symptom exacerbation.

PMID- 8985622
TI  - Head-up tilt table test: how far and how long?
AB  - There is great variation between laboratories in the angle and duration of tilt
      used in the head-up tilt table test. We compared the hemodynamic response to
      three sequential randomized 20-min tilts of 60 degrees, 80 degrees and 90 degrees
      in 20 normal subjects. We studied 66 patients to determine the duration of tilt
      needed to document three types of orthostatic intolerance. Blood pressure and
      heart rate were monitored non-invasively. Thirty-nine patients with orthostatic
      hypotension of diverse causes and 17 patients with orthostatic tachycardia plus
      were tilted to 90 degrees for 10 min. Ten patients with vasovagal syncope were
      tilted to 90 degrees for 30 min. A multivariate analysis of variance performed to
      assess the hemodynamic responses to 60 degrees, 80 degrees and 90 degrees tilts
      did not show a statistically significant difference (F = 0.459). Logistic
      regression analyses revealed that the duration of tilt required to document
      orthostatic hypotension was 5 min (73% cases correctly identified), orthostatic
      tachycardia plus 10 min (86.5% cases correctly identified) and neurally mediated
      syncope 10 min (86.5% cases correctly identified). Tilt duration is a more
      important variable than tilt angle and the duration of the tilt should depend on
      the suspected cause of orthostatic intolerance.

PMID- 8985623
TI  - The effects of midazolam and ephedrine on post-exercise autonomic chronotropic
      control of the heart in normal subjects.
AB  - Benzodiazepines may induce hypotension by inhibiting the pressor response.
      Ephedrine has adrenergic effects on the circulation. After exercise, changes in
      cardiovascular control impair orthostatic tolerance. The impaired pressure
      response can be compensated for by chronotropic control of the heart. We studied
      the effect of midazolam and ephedrine on post-exercise cardiac autonomic
      chronotropic control in six 21-year-old female volunteers, who received single
      doses of 15 mg midazolam, 50 mg ephedrine, or placebo orally according to a
      placebo-controlled, double-blind, crossover design. After exercise, the subjects
      assumed the supine position for rest, then a -10 degrees head-down position
      followed by a 70 degrees head-up position. Power spectral analysis of heart rate
      variability for 7 min and steady-state brachial arterial blood pressure were
      measured in each position. After administration of midazolam, three subjects had
      an abnormal fall in their arterial blood pressure (with one presyncope) as a
      response to head-up tilt. Changes in heart rate variability exceeded those seen
      during placebo treatment (p < 0.01) and involved oscillations, suggesting
      activation of both sympathetic and parasympathetic dynamics. After ephedrine
      administration, arterial blood pressure increased during head-down tilt, but
      parasympathetic dynamics to the heart were dampened. Head-up tilt induced
      increased sympathetic stimulation of the heart and a sympathicotonic
      cardiovascular response (p < 0.01). In conclusion, midazolam induced unexpectedly
      great changes in dynamic cardiac control during cardiovascular stimulation.
      Ephedrine increased tonic sympathetic activity and stabilized the neural
      circulatory control of the heart by immobilizing dynamic parasympathetic
      activation.

PMID- 8985625
TI  - ABO antigen blood-group compatibility in corneal transplantation.
AB  - Our objective was to evaluate the effect of ABO antigen blood-group compatibility
      on corneal allograft rejection. The 199 penetrating keratoplasties performed
      between 1985 and 1994 were analyzed retrospectively for ABO compatibility and the
      occurrence of irreversible allograft rejection. Of these, 72 were considered high
      risk transplants, as there was significant vascularization of the recipient
      cornea or a history of irreversible corneal allograft rejection or both. One
      hundred twenty-seven were low-risk transplants. The data were analyzed by using
      the Kaplan-Meier method and compared with the log-rank test. Overall, the
      estimated 1-year graft survival was 83.9% in the low-risk group and 61.4% in the
      high-risk group (p = 0.001). The estimated 1-year rejection-free graft survival
      was 89.8% in the low-risk group and 67.1% in the high-risk group (p = 0.0002). In
      the high-risk group, graft survival (p = 0.008) and rejection-free graft survival
      (p = 0.0002) were higher in the ABO-compatible subgroup than in the ABO
      incompatible subgroup. In the low-risk group, graft survival and rejection-free
      graft survival of the ABO-compatible and ABO-incompatible subgroups were similar.
      ABO compatibility may be effective in preventing irreversible allograft rejection
      in high-risk recipients.

PMID- 8985624
TI  - Vasopressin release during orthostatic hypotension after cardiac transplantation.
AB  - At the time of cardiac transplantation all nerves from the donor ventricles are
      cut. These nerves may regrow, but there is no method of measuring any regrowth.
      Arginine vasopressin (AVP) release was studied during hypotension induced by head
      up tilt and lower body negative pressure (LBNP) in transplant recipients and in
      normal controls. Subjects were tilted to 60 degrees for up to 60 min or until
      symptomatic. Lower body negative pressure (40 mmHg) was applied for 10 min after
      30 min rest. Seven of 17 transplant recipients and 11 of 12 controls became
      symptomatic during tilt testing, and 9 of 12 controls and 9 of 17 transplant
      recipients became symptomatic after 10 min of LBNP. Symptoms during tilt did not
      predict symptoms during LBNP. Resting AVP levels were similar but osmolality was
      greater in transplant recipients. Resting haematocrit was reduced, and atrial
      natriuretic peptide increased in transplant recipients, suggesting increased
      plasma volume. In symptomatic subjects, changes in humoral concentrations were
      similar when compared between transplant recipients and normals, except that the
      rise in AVP at the time of symptoms was reduced in transplant recipients, with a
      comparable drop in blood pressure consistent with persistent cardiac afferent
      denervation in a subset of transplant recipients.

PMID- 8985626
TI  - Preoperative risk factors for surface disease after penetrating keratoplasty.
AB  - We sought to identify the types of, prevalence of, and predisposing factors for
      the development of surface keratopathy after penetrating keratoplasty. We
      reviewed the records of 120 corneal grafts performed over a 15-month period.
      Twenty patients were excluded from the study. Fifty-three men and 47 women
      composed the group studied. All transplants were performed by the same surgeon.
      Retrospective data from patients' records were gathered preoperatively and from
      postoperative visits at 1 week and at 1, 2, 3, and 4 months. Data included
      preoperative medical and demographic data, operative time, postoperative
      medication regimens, assessment of the presence and degree, if present, of
      punctate epithelial keratopathy (PEK), hurricane keratopathy, macroepithelial
      defects, microcystic edema, bullous edema, and filamentary keratitis. In
      addition, information on the donor material was recorded. Surface disease and
      normal groups were compared to identify risk factors for the occurrence of
      surface abnormalities. Thirty-three of the patients demonstrated persistent
      surface abnormalities. Coarse PEK was the most common surface abnormality in the
      sample studied and was most prominent in the first week after surgery.
      Postoperative surface keratopathy was not statistically associated with
      preoperative diagnosis, donor age, death-to-preservation time, preservation-to
      surgery time, or donor epithelial status. However, corneal recipients in the
      group with surface keratopathy were significantly older (mean, 68.7 years) than
      patients in the group with no surface abnormalities (mean, 52.6 years; Mann
      Whitney U test, p < 0.001). Although many factors may contribute to the normal
      integrity of the corneal surface after keratoplasty, recipient age is of key
      importance in the development of surface disease.

PMID- 8985627
TI  - Comparison of topical timolol gel to oral acetazolamide in the prophylaxis of
      viscoelastic-induced ocular hypertension after penetrating keratoplasty.
AB  - PURPOSE: Viscoelastic-induced ocular hypertension following penetrating
      keratoplasty (PK) may result in endothelial cell loss and optic nerve damage.
      METHODS: In a prospective, randomized, masked trial, two doses of oral sustained
      release acetazolamide were compared to a single dose of topical 0.5% timolol gel
      after 40 PKs. RESULTS: The mean preoperative intraocular pressure (IOP) was 17.4
      mm Hg for the oral acetazolamide group and 16.7 mm Hg for the timolol gel group.
      The mean IOP on the first postoperative day was 17.9 mm Hg with oral
      acetazolamide and 12.9 mm Hg with timolol gel. One patient developed significant
      adverse reactions with oral acetazolamide; there were no adverse reactions with
      timolol gel. CONCLUSION: Prophylactic use of timolol gel for viscoelastic-induced
      ocular hypertension after PK appears to offer better IOP control than oral
      acetazolamide, with potentially fewer adverse systemic effects.

PMID- 8985628
TI  - Thirty years of penetrating keratoplasty in Israel.
AB  - We studied the indications for keratoplasty and their changes during 30 years in
      Israel by retrospective evaluation of pathologic records of 1,018 corneal buttons
      (from 1961 to 1990). The population included 634 (62.3%) male patients and 384
      (37.7%) female patients. Keratoconus (n = 222, 21.8%) was the most common
      indication, followed by corneal graft failure (n = 113, 11.1%), herpetic
      infections (n = 95, 9.3%), ocular trauma (n = 87, 8.5%), scarring (n = 74, 7.3%),
      pseudophakic bullous keratopathy (n = 72, 7.1%), nonherpetic infections (n = 71,
      7.0%), and other indications. Whereas ocular infections were the most common
      indications for keratoplasty before 1970, keratoconus has been the most common
      indication since 1970. Pseudophakic bullous keratopathy became the second most
      common indication (13.8%) between the years 1981 and 1990. The number of
      keratoplasties increased in Israel during the past three decades, and the low
      percentage of pseudophakic bullous keratopathy is related to the types of
      intraocular lenses that we implanted in the late 1970s and the early 1980s.

PMID- 8985629
TI  - Evaluation of infectious crystalline keratitis with confocal microscopy in a case
      series.
AB  - We sought to determine whether there are unique findings in infections
      crystalline keratitis (ICK) examined by confocal microscopy and if confocal
      microscopy is predictive for bacteriology in ICK. A retrospective review of
      consecutive patients with a presumed diagnosis of ICK by slit-lamp examination
      was performed. These patients were then examined with confocal microscope and
      cultured. Sixteen patients were identified by biomicroscopy. Average age was 71
      years; 12 of 16 patients were women; 10 of 16 had prior penetrating keratoplasty;
      and 12 of 16 were taking topical steroids. Confocal microscopy revealed a
      variable appearance to the crystals in the corneal stroma. Eight of 16 patients
      had distinct needle-like deposits at varying depths in the stroma, and eight had
      amorphous deposits grouped at different levels of the stroma. The results of
      confocal microscopic examination resembled the reported histopathology with
      clusters of deposits, but its current resolution does not allow identification of
      bacterial morphology. There was no correlation of morphology with culture
      results. Organisms were recovered in 12 of 16 patients by culture. In 10 of 16
      patients, the infection was successfully treated with topical antibiotics,
      usually cefazolin. Crystal morphology of ICK can be observed by confocal
      microscopy. No pathognomonic, single pattern for this disease is seen with the
      confocal microscope. The latter may be an aid in determining the clinical
      response to treatment.

PMID- 8985630
TI  - Diagnosis of Aspergillus keratitis in vivo with confocal microscopy.
AB  - Confocal microscopy provides a new, noninvasive way of imaging the human cornea
      in vivo. One of its most important clinical uses is the diagnosis and management
      of infectious keratitis. The authors used tandem scanning confocal microscopy to
      image the corneas in two culture-proven cases of Aspergillus keratitis. Fungal
      hyphae were imaged as high-contrast filaments 6 microns in diameter from 60 to
      400 microns in length. Confocal microscopy may be a fast and safe diagnostic tool
      in determining the presence of fungal hyphae in vivo within the human cornea.

PMID- 8985631
TI  - Infantile ulcerative keratitis secondary to congenital entropion.
AB  - Congenital entropion is a rare eyelid anomaly that can cause chronic corneal
      erosions or ulceration. The diagnosis may be easily overlooked by both the
      pediatrician and the ophthalmologist, particularly when the lids are tightly
      closed in the crying child. We present three cases of congenital entropion
      associated with corneal ulceration. Each patient underwent a complete
      ophthalmologic examination. Examination under anesthesia, including corneal
      scrapings for culture and photography, was performed before surgical repair of
      the entropion. There were two cases of lower lid entropion and one case of upper
      lid entropion. In all three cases symptoms were present since birth, and the
      diagnosis was overlooked by the treating pediatrician. Corneal ulceration
      ultimately developed in all three cases. Cultures revealed Staphylococcus aureus
      in one case, and coagulase negative Staphylococcus in another case. Cultures were
      negative in one case. In all three patients the ulcers healed rapidly after
      surgical entropion repair. Congenital upper or lower lid entropion is an uncommon
      condition that does not spontaneously improve and is an important cause of
      corneal ulceration in infants. Recognition of this condition is often difficult,
      and early surgical intervention to repair the lid deformity may help to avoid
      permanent corneal scarring and visual loss.

PMID- 8985632
TI  - Histopathology and molecular cytogenetics of a corneal opacity associated with
      the trisomy 8 mosaic syndrome (46,XY/47,XY, +8).
AB  - The trisomy 8 mosaic syndrome (Tr8MS), karyotype 46,XY/47,XY, +8, is a rare
      multisystem disorder that may be associated with corneal opacity. We report the
      case of a dysmorphic infant with multiple congenital abnormalities referred to
      our unit with a congenital corneal opacity. Subsequent chromosomal analysis of
      peripheral leucocytes demonstrated constitutional Tr8MS. At 4 years of age,
      lamellar keratoplasty was performed. Histological examination confirmed the
      lesion to be consistent with a corneal choristoma. Cytogenetic studies using in
      situ hybridisation techniques showed the presence of trisomic cells in cell
      culture derived from the tissue in higher proportion (92%) than in the blood
      (44%). Amplification of the c-myc oncogene on chromosome-8 could not be detected
      in cells cultured from the corneal lesion. Although not proof, these findings
      lend support to the concept of the corneal lesion representing a focus of viable
      trisomic cells rather than an inflammatory response to a nidus of effete cells.

PMID- 8985633
TI  - Treatment of inflamed pterygium and pinguecula with topical indomethacin 0.1%
      solution.
AB  - PURPOSE: To evaluate the effect of topical indomethacin 0.1% on signs and
      symptoms in inflamed pterygium and pinguecula. METHODS: Fifty-one consecutive
      patients who had inflamed pterygium (n = 32) or pinguecula (n = 19) were studied
      in a randomized, double-masked, controlled way. Objective signs (conjunctival
      congestion, redness, edema, and staining of cornea) and subjective complaints
      (photophobia, pain, foreign-body sensation, discomfort, and tearing) were
      evaluated and scored. In addition, we evaluated total signs, total symptoms, and
      total score. Group 1 (n = 25) received topical indomethacin 0.1% solution and
      group 2 (n = 26) received a placebo six times daily for 3 days, then four times
      daily for 11 days. Patients were examined before and at days 3, 7, and 14 after
      the treatment began. RESULTS: In group 1 at day 3, the scores of total signs,
      total symptoms, and total score decreased (p = 0.001), and they further decreased
      after 14 days (p = 0.02 to p = 0.05). In group 2 at day 3 these parameters also
      significantly decreased (p = 0.01 to p = 0.02), but no further improvement
      occurred after 14 days. Comparing groups 1 and 2 revealed a decrease in scores in
      group 1 for total signs, total symptoms, and total score at days 3, 7, and 14 (p
      = 0.03 to p = 0.002) except for total signs after 14 days (p = NS). All the
      patients reported mild stinging for < 1 min after administration of the drops.
      CONCLUSIONS: This study indicates that topical indomethacin solution 0.1% is a
      useful treatment for inflamed pterygium and pinguecula.

PMID- 8985634
TI  - Photoastigmatic keratectomy for correction of astigmatism in corneal grafts.
AB  - BACKGROUND: The efficacy and safety of excimer laser photoastigmatic refractive
      keratectomy (PARK) for treatment of astigmatism after penetrating keratoplasty
      (PKP) was evaluated in this study. METHODS: A VisX 20/20 excimer laser was used
      to correct the regular astigmatic component of the grafts. The epithelium was
      removed manually in seven cases and in three patients with the PTK mode of the
      laser. The results were analyzed for uncorrected visual acuity (UCVA), best
      corrected acuity (BCVA), haze, and changes in the cylinder and axis. The
      vectorial change in astigmatism was measured using Alpins' method. RESULTS:
      Preoperative astigmatism ranged from 3.50 to 11.25 D (mean, 5.98 +/- 2.28) and
      the mean attempted correction of astigmatism was 6.28 +/- 1.56 D (range, 3.50
      9.00 D). The induced reduction of net corneal astigmatism was 48.1%. The vector
      corrected astigmatism, which was 6.40 +/- 3.49 D at 1 month postoperatively, was
      reduced at 12 months to 4.28 +/- 2.42 D. The Alpin Success Index varied in the
      range 0.06 to 1.0. Although the UCVA improved by > or = 2 lines in 60% of the
      eyes, the BCVA decreased in 40% of the eyes and three patients required a
      reoperation. CONCLUSION: Although PARK is relatively safe and effective in
      reducing post-PKP cylinder and improves UCVA, the frequently and surprisingly
      late-developing corneal haze often impairs the BCVA.

PMID- 8985635
TI  - Computer simulation of centration effects on corneal-topography analysis of
      excimer laser photorefractive keratectomy ablations.
AB  - Excimer laser photorefractive keratectomy (PRK) procedures photoablate the
      central optical zone, potentially altering the corneal vertex normal and thus the
      corneal topography (CT) system reference axis. Anterior corneal surface
      coordinates (x, y, and z) were computer generated to simulate spherical and PRK
      ablated corneal surfaces. Power maps were reconstructed by using surface tangents
      relative to various assumed CT reference axes, the original and displaced vertex
      normals. The simulation process eliminated focus, alignment, and surface
      reconstruction errors. A simulated 5.00-D myopic PRK decentered 1 mm from the
      vertex produced a new corneal vertex 0.13 mm from the original position. Axial
      power-map generation by using this new reference axis produced a spherical
      keratectomy with astigmatic untreated periphery. This computer simulation
      demonstrates that reference axis changes are significant for even modest PRK
      decentration and can explain apparent steepening in untreated corneal areas. CT
      users should be aware that pre- and postoperative CT power maps may not be
      directly comparable.

PMID- 8985636
TI  - Ocular penetration and pharmacokinetics of topical fluconazole.
AB  - The high bioavailability and low toxicity of fluconazole, a stable, water
      soluble, low-molecular-weight bis-triazole antifungal, makes it a good candidate
      for consideration as a topical ocular agent. The penetration of fluconazole
      (0.2%) into the corneas and aqueous humors of New Zealand white rabbits was
      assayed by gas liquid chromatography (GLC). Peak corneal levels occurred
      essentially immediately at 5 min in the corneas [debrided, 8.2 +/- 1.2
      micrograms/g; nondebrided, 1.6 +/- 0.6 microgram/g; (mean +/- SEM)] and at 15 min
      after application in the aqueous [debrided, 9.4 +/- 2.3 micrograms/ml;
      nondebrided, 1.6 +/- 0.6 microgram/ml; (mean +/- SEM)]. Estimating from
      semilogarithmic plots of the data, the halflife (t1/2) in the debrided eyes was
      15 min; in the nondebrided eyes, t1/2 was 30 min. A loading dose of a 20
      microliter drop per min for 5 min yielded levels of 59.9 +/- 11.3 micrograms/g
      (mean +/- SEM) in the debrided corneas and 32.4 +/- 1.9 micrograms/ ml (mean +/-
      SEM) in the corresponding aqueous humor. A regimen consisting of this loading
      dose followed by one 20 microliters drop/h for 6 h showed 45.9 +/- 3.5
      micrograms/g (mean +/- SEM) in the debrided corneas and 8.8 +/- 1.7 micrograms/ml
      (mean +/- SEM) in the corresponding aqueous. The same regimen yielded values of
      3.1 +/- 0.2 micrograms/g in the nondebrided corneas and 1.3 +/- 0.2 micrograms/ml
      (mean +/- SEM) in the aqueous. Minimal inhibitory concentrations (MIC) at 24 h
      for yeasts ranged from < 1.25 to 20 micrograms/ml, for hyaline molds from 2.5 to
      > 20 micrograms/ml, and dematiaceous molds from < 1.25 to > 20 micrograms/ml.
      Topical fluconazole exhibits pharmacokinetics and selective MICs that merit
      further evaluation for its ophthalmic use as a topical antifungal agent.

PMID- 8985637
TI  - Characterization of SV40-transfected cell strains from rabbit keratocytes.
AB  - The process of corneal wound healing involves the transformation of adjacent
      corneal keratocytes to myofibroblast-like cells characterized by the development
      of prominent microfilament bundles containing alpha-smooth muscle-specific actin
      (alpha-SM), a contractile protein thought to be important in mediating wound
      contraction. Recent studies have shown that the expression of alpha-SM in
      cultured corneal keratocytes can be induced by serum and TGF beta 1. To study the
      cellular and molecular mechanisms underlying this transformation process and to
      begin to identify the role of alpha-SM in wound contractile events, we generated
      immortalized rabbit corneal cell strains with extended life by using SV40
      transfection. Two unique strains were isolated (TRK-36 and TRK-43). TRK-36, which
      appears similar to normal corneal keratocytes, maintains a stellate, keratocyte
      morphology when grown in the absence of serum and transforms to a myofibroblast
      like cell when treated with TGF beta 1 (1 ng/ml), as indicated by the induced
      expression of alpha-SM actin. TRK-43 exhibits features characteristic of
      myofibroblasts in that it constitutively expresses alpha-SM actin under serum
      free conditions. Both strains show in vitro contraction of collagen gels < or =
      80% in 24 h in serum-containing medium. Interestingly, under serum-free
      conditions, TRK-43 cells showed significantly greater contraction of collagen
      gels compared with those of TRK-36. Overall, the establishment and further study
      of these cell strains may provide important insights into the molecular
      mechanisms underlying myofibroblast transformation.

PMID- 8985638
TI  - The Tampa Trephine technique with cat corneal endothelium.
AB  - The Tampa Trephine (Martin Marietta Speciality Components, Largo, FL, U.S.A.)
      penetrating keratoplasty technique uses a 7.0-mm corneal donor button with six
      rectangular 1 x 2-mm tabs of Bowman's layer, 75 microns in thickness, which are
      inserted into the recipient stroma beneath Bowman's layer. We evaluated the
      safety of the Tampa Trephine tissue-trephination method on the cat corneal
      endothelium combining vital staining and scanning electron microscopy, comparing
      it with the standard Weck trephination technique. The Tampa Trephine tissue
      trephination produces a donor button with a 6.7-mm diameter central area of
      normal endothelium. Localized peripheral areas of cellular loss, endothelial and
      Descemet's tears, endothelial detachment, and folding along the border of the
      trephination were observed with the Tampa Trephine method, all located in an area
      of < or = 150 microns, adjacent to the edge of the button. Standard trephination
      induced a localized peripheral area of endothelial damage < 50 microns in
      extension from the donor edge. A theoretic maximal 8.4% peripheral endothelial
      cell loss is induced with the Tampa Trephine trephination method, compared with a
      2.8% loss with the standard procedure. The peripheral location of the alterations
      after the Tampa Trephine does not hinder the viability of the corneal
      endothelium, as it has been clinically observed.

PMID- 8985639
TI  - Anterior segment prosthesis development: retinal function following anterior
      segment removal.
AB  - Replacement of the entire anterior segment of the eye is a very ambitious and
      complex endeavor and it is not known whether the retina remains functional when
      the anterior structures have been removed. We used routine histo-pathologic
      evaluation and electroretinographic measurements to determine the structural and
      functional status of rabbit retinas following surgical removal of the internal
      anterior structures (iris, ciliary body, and lens) and replacement of the
      vitreous with silicone oil. In some cases, we were able to record both a scotopic
      and a photopic electroretinographic response as long as 15 weeks after complete
      removal of the internal anterior segment structures. Although many hurdles remain
      and more efficacious surgical techniques and biomaterials need to be developed,
      our results suggest that, in the rabbit, the retina may continue to function in
      the absence of critical anterior segment structures.

PMID- 8985640
TI  - In vitro amoebicidal activity of propamidine and pentamidine isethionate against
      Acanthamoeba species and toxicity to corneal tissues.
AB  - Effective chemotherapy for Acanthamoeba keratitis has been hampered because of
      the marked resistance of the parasites to a variety of antimicrobial agents. In
      view of the fact that topical Brolene (propamidine isethionate) and neosporin are
      currently considered to be the medical treatment of choice in Europe, we sought
      to determine whether pentamidine may be equally effective, because the drug is
      more readily available to ophthalmologists in the United States. In this study,
      we compared the amoebicidal activity of the Brolene (commercial product),
      propamidine isethionate and pentamidine isethionate (Pentam) in vitro against
      three different species of Acanthamoeba, and the drugs' corresponding
      biocompatibility with rabbit corneal epithelial and endothelial cell cultures.
      The results indicated that there were significant species differences in drug
      sensitivity. Propamidine (> 1,000 micrograms/ml) was clearly less effective than
      pentamidine (> 125 micrograms/ml) against A. castellanii, although equivalent
      potency (> 250 micrograms/ml) was observed against A. polyphaga. On the other
      hand, propamidine (> 31.25 micrograms/ml) was slightly more effective than
      pentamidine (> 62.5 micrograms/ml) against A. hatchetti. Both drugs were also
      relatively nontoxic after short-term contact with cell cultures, even though the
      highest concentration of pentamidine caused low-grade injury to the superficial
      epithelium and reversible membrane damage to the endothelium. Steady-state levels
      of propamidine at effective amoebicidal concentrations, however, were much more
      toxic than pentamidine, which indicated that the drug has a much lower
      therapeutic index. Our data suggest that pentamidine may be an effective
      therapeutic option because of its potency and low toxicity.

PMID- 8985642
TI  - ICAM-1 expression in corneal epithelium of a patient with vernal
      keratoconjunctivitis: case report.
AB  - Recent reports have demonstrated the expression of intercellular adhesion
      molecule-1 (ICAM-1; CD54) on the epithelium in various allergic diseases and
      inflammatory conditions, including the bronchial epithelium of patients with
      allergic asthma, conjunctival epithelium of allergic patients after allergen
      specific challenge, and corneal epithelium of rejected corneal allografts. We
      investigated the presence of ICAM-1 expression on the corneal epithelium from a
      patient with vernal keratoconjunctivitis (VKC). Immunohistochemical staining of
      the diseased cornea demonstrated abundant ICAM-1 expression on the corneal
      epithelium. Immunoreactive ICAM-1 appeared to localize primarily to the cells of
      the basal and middle layers of the corneal epithelium. No staining was detected
      on the ocular surface epithelium. The normal, healthy cornea demonstrated no
      significant ICAM-1 expression on any of the epithelial layers, similar to that
      previously reported. To the best of our knowledge, this is the first report of
      ICAM-1 expression on the corneal epithelium from a patient with VKC.

PMID- 8985641
TI  - Effect of hybrid peptides of cecropin A and melittin in an experimental model of
      bacterial keratitis.
AB  - Synthetic peptides, ranging from 12 to 18 residues, containing partial sequences
      from natural cecropin A and melittin were tested for activity in an experimental
      pseudomonas keratitis model in rabbits. In separate experiments, two Pseudomonas
      aeruginosa strains: (a) a clinical isolated strain, and (b) an American Type
      Culture Collection (ATCC) strain, were inoculated into the stroma of one cornea
      of each rabbit. Peptides were topically applied at 0.1% in phosphate-buffered
      saline (PBS) and compared with PBS alone and 0.3% gentamicin eye drops. Clinical
      evaluation, based on the McDonald-Shadduck scale, was performed during a > 48-h
      period after the bacterial inoculation. The peptide-treated animals showed
      significantly lower (p < 0.05) inflammatory signs and lower anterior-segment
      bacterial damage compared with PBS-treated animals, after the first 6 h. The
      antiinflammatory/antimicrobial activity was non significantly differnt (p > 0.05)
      from that in animals treated with gentamicin. We conclude that peptides keeping
      the sequence KWKLFKK from cecropin A and at least the sequence VLKVL from
      melittin show promise as novel agents in topical ocular therapy of bacterial
      keratitis.

PMID- 8985643
TI  - An unusual case of elastofibroma oculi.
AB  - A 22-year-old female college student from the southwestern United States was
      first seen with progressive fluffy white growths over both corneas nasally and a
      history of chronic allergies and extensive sun, wind, and chlorine exposure as a
      competitive swimmer. The lesions were superficial, elevated, crescent-shaped,
      vascularized, and extended from the limbal conjunctiva onto the peripheral cornea
      nasally. The lesions were composed of an unencapsulated thick fibrovascular
      pannus with numerous fibrocytes, chronic inflammatory cells and mast cells, and
      abundant linear and wavy elastinophilic profiles, but no adipose tissue.
      Ultrastructurally, the elastinophilic structures were immature elastic fibers
      arranged in globules and bundles within a thick collagenous matrix. No mature
      elastic fibers were found. A few areas of elastotic degeneration were also found.
      This lesion resembled elastofibromas that have been reported more commonly in the
      subcapsular region and only once in the ocular region. Previous reports debated
      whether the elastic material in elastofibromas is derived from excessive
      production of elastic fibers by activated fibrocytes or from elastotic
      degeneration of collagen. In our case, both processes occur and are presumed to
      result from excessive ultraviolet radiation, wind and chlorine exposure, and
      perhaps, chronic inflammation; features that have been ascribed to the
      pathogenesis of pingueculae and pterygia.

PMID- 8985644
TI  - Iris ischaemia following penetrating keratoplasty for keratoconus (Urrets-Zavalia
      syndrome)

PMID- 8985645
TI  - Modern penetrating keratoplasty: an iatrogenic indication?

PMID- 8985646
TI  - Molecular and cellular aspects of the glucagon receptor: role in diabetes and
      metabolism.
AB  - The role of glucagon in eliciting hyperglycaemia has been studied extensively for
      more than 20 years. However, little has been learned about the specific targeted
      tissues and intracellular effects of glucagon since no specific causal
      interactions have been established between glucagon and the so called "glucagon
      binding site". Indeed, glucagon and related hormones, such as glucagon-like
      peptide, glucoin-sulinotropic hormone and vasoactive intestinal peptide acting
      through different receptors, have similar effects in hyperglycaemic syndromes.
      The recent cloning of the glucagon receptor (GR) encoding sequences has clarified
      many aspects of its structure as well as its integrated role in the cell and the
      entire body. The GR contains seven transmembrane domains and is characterised by
      a conserved G-protein binding site and a large amino-terminal domain containing
      the amino-acid residues mainly involved in ligand binding. The GR is expressed in
      liver, pancreatic beta cells, kidney, adipose tissues, heart, and vascular
      tissues, as well as in some region of brain, stomach, and adrenal glands. The
      precise role of the GR in most of these tissues is still unclear. However, with
      the cloning of the coding sequences, genetic manipulations of the GR should
      provide specific indications of the normal metabolic effects of the GR system on
      these tissues and how altered glucagon signalling might contribute to the
      development of diabetes.

PMID- 8985647
TI  - Assessment of residual insulin secretion in diabetic patients using the
      intravenous glucagon stimulatory test: methodological aspects and clinical
      applications.
AB  - Defective insulin secretion plays a crucial role in insulin-dependent (Type 1)
      and non-insulin-dependent (Type 2) diabetes mellitus as well as in many secondary
      forms of the disease. Glucagon is a potent stimulus for the islet beta-cell, and
      intravenous bolus injection of 1 mg glucagon has been widely used to assess
      endogenous insulin secretion for clinical or research purposes. Plasma C-peptide
      levels (less commonly insulin) are usually measured immediately before and 6 min
      after glucagon injection. The C-peptide response to glucagon is well-correlated
      with the beta-cell response to mixed meals or other stimuli commonly used to
      characterize endogenous insulin secretion (oral or intravenous glucose, standard
      meals, arginine, etc.) and has the advantage of shorter duration and simple
      standardization. The glucagon test shows good intra-subject reproducibility,
      although in diabetic patients it may be influenced by variable prevailing blood
      glucose levels. Several applications of the glucagon test have been developed. In
      Type 1 diabetes, the glucagon test has been used to discriminate between patients
      with and without residual insulin secretion. This can be especially important
      during the first few months, or even years, following initiation of insulin
      therapy when attempts to stop the immunological destruction of the beta-cell are
      made. Assessment of endogenous insulin secretion is also important after pancreas
      or islet transplantation. In patients with Type 2 diabetes mellitus, in which
      residual endogenous insulin secretion is common, characterization of the disease
      may help in the choice of therapy for the individual patient (insulin,
      sulphonylureas or combined therapy). Thus, the glucagon test is a simple,
      reliable and useful tool for clinical evaluation of diabetes mellitus.

PMID- 8985648
TI  - Recent advances in diabetic nephropathy: how big a culprit is glucose?

PMID- 8985649
TI  - Are the implications of the Diabetes Control and Complications Trial (DCCT)
      feasible in daily clinical practice?
AB  - The Diabetes Control and Complications Trial was conducted in heavily-equipped
      centres on a selected and motivated patient cohort. The aim of the present study
      was to evaluate at one-year follow-up the results of intensive insulin therapy in
      patients with insulin-dependent diabetes mellitus attending a department of
      diabetology. From October 1, 1993, to December 31, 1994, all our hospitalised
      patients under 55 years of age with HbA1c levels above 8% and receiving 2 daily
      insulin injections were offered the opportunity to shift to 3 daily injections
      (short-acting insulin in the morning and at midday, and a mixture of short-acting
      and intermediate insulin in the evening). Patients were instructed to increase
      blood glucose self-monitoring and to see their diabetologist more often (once
      every two months). Five patients refused and 45 accepted this proposal: 22 women
      and 23 men (mean age 31.8 +/- 10.9 yr), BMI 23.5 +/- 2.9 kg/m2, duration of
      diabetes 12.8 +/- 10.1 yr, HbA1c 10.0 +/- 2.0%. Five patients were lost to follow
      up, 2 asked to have their medical file transferred, 3 returned to 2 daily
      injections, and 5 consulted only once during the year of follow-up. For the 29
      patients seen after one-year follow-up, the decrease in HbA1c levels from 10.0 +/
      1.9% to 9.5 +/- 1.8% was not statistically significant. Sixteen patients
      complained of increased occurrence of hypoglycaemia (3 comas). In routine
      clinical practice, the prescription of intensive insulin therapy to non-selected
      insulin-dependent diabetic patients can be associated with a high number of
      patients lost to follow-up (17% in our study). An increase in the number of daily
      insulin injections will improve glycaemic control only if self-monitoring and
      medical surveillance are also intensified. However, many long-term poorly
      controlled insulin-dependent diabetic patients are reluctant to comply with these
      recommendations.

PMID- 8985650
TI  - Improved lipoprotein surface and core lipid composition following intraperitoneal
      insulin delivery in insulin-dependent diabetes mellitus.
AB  - To determine whether insulin delivered into portal circulation by an implanted
      pump reversed abnormalities in lipoprotein composition in insulin-dependent
      diabetes mellitus, 10 well-controlled normolipidaemic patients were studied after
      conventional intensive sub-cutaneous (ISC) insulin management and then 3 and 6
      months after intraperitoneal pump implantation (IP). Glycated haemoglobin (ISC:
      6.9 +/- 1.7% vs. IP-3 months 6.3 +/- 0.7; IP-6 months 6.3 +/- 0.8; mean +/-
      S.D.), plasma triglyceride and cholesterol levels, and the cholesterol content of
      HDL2 and HDL3 were normal and not significantly changed during these treatments.
      Fasting free insulin concentrations measured before and after 6 months of IP fell
      by more than half (ISC 8.22 +/- 6.5 vs IP 2.77 +/- 2.4 mU/ml; p < 0.025). The
      plasma-free cholesterol/lecithin ratio, a potential new cardiovascular risk
      factor, was increased during ISC, declined progressively after 3 months of IP,
      and approached normal by 6 months (ISC 0.96 +/- 0.37 mol/mol vs. IP-3 months 0.91
      +/- 0.34; IP 6 months 0.86 +/- 0.10; reference group 0.83 +/- 0.33). In all
      lipoprotein fractions, sphingomyelin concentrations tended to fall, and lecithin
      concentrations to rise progressively during IP. As a result, the
      sphingomyelin/lecithin ratio, an index of the surface rigidity of lipoproteins,
      declined. The fact that some of the compositional modifications associated with
      ISC were reversed when insulin was administered intraperitoneally suggests that
      they may have been iatrogenic and resulted from high systemic insulin levels.

PMID- 8985651
TI  - Distribution of fasting serum insulin measured by enzyme immunoassay in an
      unselected population of 4,032 individuals. Reference values according to age and
      sex. D.E.S.I.R. Study Group. Donnees Epidemiologiques sur le Syndrome d'Insulino
      Resistance.
AB  - As hyperinsulinaemia has been shown to be a risk factor for non-insulin-dependent
      diabetes, cardiovascular disease and hypertension, the measurement of serum
      insulin levels may provide an additional early screening test for these diseases.
      Biological assaying of insulin is now facilitated by the IMx-Abbott kit, an
      enzyme immunoassay which does not cross-react with proinsulin and thus provides
      more specific insulin determination than conventional methods. Fasting insulin
      concentrations were determined in a population of 4,032 men and women 30 to 64
      years of age, all volunteers for a medical check-up. Concentrations were slightly
      higher for men in all age-classes (median values of 5.9 and 5.4 microU/ml
      respectively for men and women). Although significant differences were found in
      serum insulin concentrations between the four age-classes for men and women,
      there were no significant differences between the three age-classes for men up to
      59 years (median: 5.8 microU/ml, 95th percentile 14.0 microU/ml) or between the
      two age-classes for women up to 49 years (5.2, 12.5). Fasting concentrations were
      increased above these age thresholds: men (6.4, 15.6), women (5.6, 14.0). The
      reference population consisted of 3,081 non-diabetic, glycosuria-negative
      subjects with a body mass index and glucose concentration lower than the 95th
      percentiles for their age and sex. The reference values for fasting insulin
      concentrations were: 1) women 30-49 years: median 5.1 microU/ml (95% confidence
      interval: 4.9-5.3), 95th percentile 11.2 microU/ml (10.9-11.9); and 2) men 30-64
      years and women 50-64 years: median 5.6 microU/ml (5.4-5.7), 95th percentile 12.6
      microU/ml (12.0-13.0).

PMID- 8985652
TI  - Experimental diabetes induces an early change in the level of the G-protein
      subunit, alpha i2, in rat intestinal mucosa.
AB  - This study was undertaken to investigate the consequences of diabetes on Gi
      protein expression and alpha 2-adrenergic receptivity in rat intestinal mucosa.
      Experimental diabetes was induced by treatment with streptozotocin.
      Quantification of alpha i-subunits by immunoblotting demonstrated that the level
      of the G alpha i2 but not the G alpha i3 subunit was markedly decreased in
      jejunum and colon membranes from diabetic rats as compared to controls. Parallel
      assessment of sympathetic innervation was performed by determination of
      norepinephrine content, measurement of tyrosine hydroxylase and monoamine oxidase
      activities, and quantification of alpha 2-adrenergic receptors in the different
      segments. At this stage of diabetes (6 weeks after streptozotocin injection),
      none of these parameters was significantly modified. Consequently, the decrease
      in G alpha i2 amount appears to be independent of the neuropathy describe in
      later stages of diabetes.

PMID- 8985653
TI  - Proteins spontaneously released by rat insulinoma (RIN) cells are anchored on
      cell membrane by a glycosyl-phosphatidyl-inositol link and inhibit increased RIN
      cell adhesion of lymphocytes from type 1 diabetic patients and non-obese diabetic
      mice in vitro.
AB  - Our group previously reported an assay for the study of lymphocyte adhesion to
      insulin-producing cells in which xenogeneic rat insulinoma (RIN) cells were used
      as targets. The present study found an increased number of RIN-cytoadherent
      lymphocytes in 63 patients with Type 1 diabetes compared with 150 control
      subjects and in 211 NOD mice compared with 104 BALB/c mice (p < 0.001). Proteins
      concentrated from spontaneous RIN cell culture supernatants inhibited increased
      RIN-adhesion of NOD splenocytes or lymphocytes from diabetic patients (p <
      0.001). In addition, increased RIN binding was dose-dependently abolished by RIN
      membrane extracts. The fact that RIN binding was inhibited by proteins from both
      membrane and the culture supernatant from RIN cells suggests that soluble
      inhibitory proteins were spontaneously released into the supernatant from a
      hydrophobic membrane-bound form. This tended to be confirmed since inhibition
      obtained with both preparations involved a 55-75 kDa HPLC protein fraction. The
      possibility that the membrane form of the inhibitory protein was anchored by a
      glycosylphosphatidylinositol (GPI) tail was evaluated. When RIN cells were
      treated with PI-PLC, their ability to bind lymphocytes from diabetic patients or
      NOD splenocytes decreased (p < 0.001) to control levels. Co-incubation with the
      55-75 kDa fraction of proteins cleaved from RIN cells by PI-PLC also lowered the
      number of RIN-adherent NOD splenocytes to control levels. SDS-PAGE and IEF
      analyses of the 55-75 kDa inhibitory fraction from RIN cell supernatant revealed
      a major band with Mr 66 kDa and PI5.4, which may correspond to a protein with
      similar characteristics noted on 2-D electrophoresis of proteins cleaved from RIN
      cells by PI-PLC. Specific labelling of GPI moieties with 3H-ethanolamine, 3H
      glucosamine, or 14C-glucosamine, as well as conversion of the hydrophobic Triton
      X114 solubilised form into a hydrophilic form after PI-PLC treatment, confirmed
      the presence of a GPI anchor in this approximately 66 kDa RIN protein, which
      could thus be the molecule inhibiting adhesion in the system. Our data suggest
      that GPI-proteins from insulin-producing cells may influence the immune system
      both in their membrane-anchored and soluble forms. When considering the binding
      model, in which beta cells were tumoral and xenogeneic to diabetic lymphocytes,
      this potential influence of GPI-proteins suggests possible implications in
      situations of lymphocyte-beta cell interaction, i.e. anti-beta cell autoimmunity,
      immune reaction against insulinomas, and reaction against islet xenografts.

PMID- 8985654
TI  - Indication for genetic linkage of the phosphoenolpyruvate carboxykinase (PCK1)
      gene region on chromosome 20q to non-insulin-dependent diabetes mellitus.
AB  - There is strong evidence that non-insulin-dependent-diabetes mellitus (NIDDM) has
      a polygenic mode of inheritance. Nevertheless, major gene effects may be involved
      in its pathogenesis, especially in forms with an early age of onset. We performed
      linkage analyses between 4 candidate genes for insulin resistance and NIDDM in a
      set of 55 multigenerational French Caucasian families, using the affected sib
      pair approach. No significant results were obtained with glycogen synthase (GSY),
      insulin receptor substrate-1 (IRS-1) and apolipoprotein C-II (APOC-II) genes.
      However, a significant trend towards linkage was found between NIDDM and the
      phosphoenolpyruvate carboxykinase gene (PCK1) located on chromosome 20q (p =
      0.005 for the mean estimated proportion of alleles shared identically by descent,
      mean IBD = 0.55), particularly among sib-pairs with diabetes diagnosed before the
      age of 46 years (p = 0.0003, mean IBD = 0.66). These results suggest that the
      PCK1 gene or a nearby locus contributes to the development of NIDDM in the French
      population.

PMID- 8985655
TI  - Glucagon-induced plasma C-peptide response in diabetic patients. Influence of
      body weight and relationship to insulin requirement.

PMID- 8985656
TI  - Beta-lactam stability in frozen microdilution PASCO MIC panels using strains with
      known resistance mechanisms as biosensors.
AB  - The stability of amoxicillin/clavulanate, piperacillin/tazobactam, cefepime,
      imipenem, and meropenem in PASCO (PASCO System, DIFCO Laboratories, Detroit, MI,
      USA) frozen microdilution susceptibility panels stored for 16 weeks at -20
      degrees C and -70 degrees C was evaluated. The increase in MIC values for the
      five American-Type Culture Collection (ATCC) quality control strains for
      susceptibility testing recommended by the National Committee for Clinical
      Laboratory Standards (NCCLS) and for 13 strains with different well-characterized
      resistance mechanisms was indicative of bioactivity deterioration. The overall
      agreement (+/- 1 twofold dilution) at purchase between the MIC values of PASCO
      frozen microdilution susceptibility panels and the standard agar dilution method
      was 97.7%. Minimum inhibitory concentration values for the associations of
      amoxicillin/clavulanate and piperacillin/tazobactam remained unchanged for the
      study period at -70 degrees C. In contrast, a carbapenem bioactivity decrease was
      detected only with strains having well-characterized resistance mechanisms from
      the 12th week onwards. At -20 degrees C, antibiotic deterioration with these
      latter strains was observed earlier than with ATCC strains: the activity of
      meropenem and imipenem remained unchanged only for the first 2 weeks, while a
      loss of activity was detected for amoxicillin/clavulanate and
      piperacillin/tazobactam at the 7th and 10th week, respectively. Cefepime was
      highly stable both at -20 degrees C and -70 degrees C. Strains with well
      characterized resistance mechanisms should be used in routine quality control
      studies of antibiotic stability for susceptibility testing panels during the
      storage period.

PMID- 8985657
TI  - Transmission of Citrobacter koseri from mother to infant documented by ribotyping
      and pulsed-field gel electrophoresis.
AB  - We describe a case in which Citrobacter koseri (formerly C. diversus) was
      transmitted from a pregnant mother with chorioamnionitis and bacteremia to her
      infant who was bacteremic at birth and in apparent septic shock. Two highly
      discriminating molecular methods, ribotyping and pulsed field gel
      electrophoresis, were used to examine restriction fragment length polymorphisms
      within the genomic DNA of maternal and infant isolates. Both techniques
      identified the maternal and infant isolates as the same strain, distinct from
      epidemiologically unrelated controls, thus confirming their common origin.

PMID- 8985658
TI  - Isolation of Shiga-like toxin producing Escherichia coli (O157 and non-O157) in a
      community hospital.
AB  - During a 25-week period (June to November 1995), stool specimens with an abnormal
      appearance (semiliquid to liquid, containing gross mucus or blood) were selected
      for testing with a new EIA method for detection of Shiga-like toxin-producing
      Escherichia coli (O157:H7 and non-O157 serotypes). The 270 specimens tested
      originated from different patients. Eleven of the 270 were positive by EIA for
      Shiga-like toxin (SLT). Escherichia coli O157:H7 was recovered from six of the
      EIA-positive specimens, and the remaining five positive samples produced non-O157
      isolates.

PMID- 8985659
TI  - Novel mechanism of macrolide resistance in Streptococcus pneumoniae.
AB  - The mechanism of macrolide resistance was examined in 73 clinical isolates of
      Streptococcus pneumoniae. Two distinct resistance phenotypes were observed: high
      level macrolides-lincosamides-streptogramin B (MLS) resistance and low-level
      macrolide resistance with lincosamide susceptibility. High-level MLS resistance
      was associated with the presence of ermAM. Strains with the low-level resistant
      phenotype (novel) were negative for ermA, ermC, ermAM, ereA, ereB and msrA by
      polymerase chain reaction (PCR) amplification with gene-specific primers.
      Ribosomes isolated from novel strains bound the same amount of [14C]-erythromycin
      as ribosomes from sensitive strains. These novel strains also did not inactivate
      the macrolide. The novel mechanism was found in 41% of the erythromycin resistant
      S. pneumoniae examined.

PMID- 8985660
TI  - Bactericidal activity of the fluoroquinolone DU-6859a alone and in combination
      with other antimicrobial agents against multiresistant enterococci.
AB  - The in vitro activity of DU-6859a (DU) alone and in combination with various
      antimicrobials was evaluated against multiresistant enterococci including some
      isolates with defined gyrA mutations. DU produced rapid in vitro killing against
      most enterococci that lacked resistance to ciprofloxacin, but it was not
      bactericidal against strains with MICs of ciprofloxacin of > or = 8
      micrograms/ml, or against one of four strains with an MIC of ciprofloxacin of 4
      micrograms/ml. The combination of DU with rifampin was antagonistic against two
      of two isolates tested. Combinations of DU and novobiocin, gentamicin, or a beta
      lactam (amoxicillin, ampicillin-sulbactam, or amoxicillin-clavulanate) were
      generally indifferent. When different beta-lactams were used together, with or
      without DU, bactericidal activity was observed against some isolates. Despite the
      absence of synergistic interactions with other agents, DU is a promising
      fluoroquinolone for use against enterococci, although prior development of
      resistance to currently available fluoroquinolones diminishes some of its effect.

PMID- 8985661
TI  - Persistent diarrhea caused by Isospora belli: therapeutic response to
      pyrimethamine and sulfadiazine.
AB  - A 54-year-old human immunodeficiency virus (HIV)-positive homosexual man
      developed overwhelming watery diarrhea and marked weight loss over a 3-week
      period. Although Entamoeba histolytica and other nonpathogenic enteric protozoa
      were observed along with Isospora belli in this patient's stool specimens, they
      were promptly eradicated after metronidazole (flagyl) treatment. The presence of
      I. belli oocysts in various stages of development in the stool and clinical
      symptoms related to Isospora infection persisted for 10 more months despite
      treatment with combined chemotherapeutic agents. Clinical and parasitiological
      resolution was ultimately achieved through an 8-week course of pyrimethamine and
      sulfadiazine.

PMID- 8985662
TI  - Recurrent bacterial peritonitis caused by Neisseria cinerea in a chronic
      ambulatory peritoneal dialysis (CAPD) patient.
AB  - We present an unusual case of recurrent (chronic ambulatory peritoneal dialysis)
      CAPD-associated peritonitis caused by Neisseria cinerea. Using DNA restriction
      fragment length polymorphism (RFLP) analysis, we determined that the recurrent
      infection was caused by reinfection with a different N. cinerea strain rather
      than relapse with the index strain and that the probable origin of the
      reinfecting organism was the patient's upper respiratory tract.

PMID- 8985663
TI  - Nontypeable Haemophilus influenzae susceptibility: effect of inoculum size and
      beta-lactamase production.
AB  - The activities of cefixime, cefpodoxime, cefprozil, cefuroxime, loracarbef, and
      amoxicillin/clavulanate against 72 clinical isolates of nontypeable Haemophilus
      influenzae were determined by using an agar dilution method. The effects of beta
      lactamase production and bacterial inoculum size were investigated. All
      antimicrobials exhibited a significant inoculum effect, demonstrating the
      importance of accurately determining inoculum size in the performance of
      antimicrobial susceptibility testing of H. influenzae.

PMID- 8985664
TI  - Medium and supplement effects on the antimicrobial activity of
      quinupristin/dalfopristin tested by agar dilution and Etest methods.
AB  - Quinupristin/dalfopristin (also known as RP-59500 and Synercid), a streptogramin
      combination has been documented as active against a wide variety of Gram-positive
      species. Broad ranges of MIC results have been observed with some species using
      acceptable susceptibility testing methods. To address the contribution of testing
      medium and supplements to this disagreement, 15 medium or supplement alterations
      were studied in a reference agar dilution format and three variations of Mueller
      Hinton agar were used for Etest (AB Biodisk, Solna, Sweden). One-third of the
      agar dilution variations produced a consistent elevation (twofold) in the
      quinupristin/dalfopristin MIC. The greatest changes were secondary to additions
      of serum and blood, pH increases, and possibly charcoal. Similarly, the Etest
      MICs for quinupristin/dalfopristin were 0.5 to 2.5 log2 dilutions higher with
      media supplemented with 5% sheep erythrocytes or when chocolated. Additional
      quinupristin/dalfopristin stability experiments in three agars indicate a two- to
      fourfold decline in potency over 21 days of storage at 2 to 5 degrees C. These
      variations in the streptogramin MIC results would be observed most frequently
      when testing fastidious species or in laboratories routinely testing all Gram
      positive bacteria in or on blood-supplemented media.

PMID- 8985665
TI  - Potential roles of tumor necrosis factor-alpha in follicular development,
      ovulation, and the life span of the corpus luteum.

PMID- 8985666
TI  - The effects of a duplication in the ovine growth hormone (GH) gene on GH
      expression in the pituitaries of ram lambs from lean and fat-selected sheep
      lines.
AB  - Growth hormone (GH) gene expression was investigated in pituitaries of 14- to 15
      month-old ram lambs from flocks selected for high (fat) or low (lean) back fat
      depth, which were also homozygous for a single GH gene allele, heterozygous or
      homozygous for a duplication in the GH gene. The pituitaries of lean sheep of all
      three GH genotypes were significantly heavier than those of fat sheep, but there
      were no pituitary weight differences between GH genotypes. No significant lean
      fat selection line- or GH genotype-specific differences were measured in
      pituitary GH concentration. However there was a significant increase (P < 0.01)
      in the total pituitary content of GH in lean compared with fat animals and a
      significant interaction between GH genotype and lean-fat selection line (P <
      0.05) was noted for GH content. No significant differences were measured in the
      relative concentration of GH mRNA, suggesting that the ratio of GH mRNA per mg
      total cellular RNA remained constant across lean-fat selection line and GH
      genotype. We conclude that the pituitary glands of Coopworth sheep selected for
      low backfat depth (lean) are bigger and have an increased GH content, but appear
      to contain similar concentrations of GH mRNA and immunoreactive GH as the
      pituitaries of fat sheep. The presence of the GH gene duplication in sheep has
      little measurable effect on the expression and storage of GH in the pituitary.

PMID- 8985668
TI  - Effects of growth hormone (GH)-releasing hormone and its analogs on GH secretion
      from cultured adenohypophysial cells in cattle.
AB  - The effects of the human growth hormone (GH)-releasing hormone (hGRF(1-44)-NH2:
      hGRF-44), bovine GRF (bGRF(1-44)-NH2: bGRF-44), and their analogs (hGRF(1-29)
      NH2, [D-Ala2]- hGRF(1-29)-NH2, bGRF(1-29)-NH2,[D-Ala2,Ala15]-bGRF(1-29)-NH2) as
      well as rat GRF(rGRF) on bovine GH release from anterior pituitary (AP) cells
      were studied in vitro in steers. The AP cells were incubated for 2 hr with the
      GRFs after preincubation for 3.5 d. Both of the hGRF-44 and hGRF(1-29)-NH2 (hGRF
      29) significantly stimulated GH release from cultured cells at doses from 10(-14)
      to 10(-8)M (P < 0.01). The analog [D-Ala2]-hGRF-29 significantly induced GH
      release in media at doses from 10(-18) to 10(-8) M (P < 0.01). The bGRF-44,
      bGRF(1-29)-NH2 (bGRF-29), and [D-Ala2, Ala15]-bGRF-29 significantly induced GH
      release in media at doses as low as 10(-18), 10(-17), and 10(-16)M, respectively
      (P < 0.01). At doses from 10(-11) to 10(-8)M, there were no significant
      differences in GH-releasing potency between the hGRFs and bGRFs. The rGRF
      significantly stimulated GH release at doses ranging from 10(-14) to 10(-8) M (P
      < 0.01). The linear regression tests showed that the hGRFs, bGRFs, and rGRF, at
      doses from 10(-14) to 10(-8)M, induced GH release in a dose-related manner (P <
      0.01). These results suggest that the hGRF, bGRF, and their analogs, as well as
      rGRF, are potent secretagogues of GH release from adenohypophysial cells in vitro
      in cattle.

PMID- 8985667
TI  - In vivo investigation of luteal function in dogs: effects of cabergoline, a
      dopamine agonist, and prolactin on progesterone secretion during mid-pregnancy
      and -diestrus.
AB  - The role of prolactin on luteal function in dogs was investigated in vivo. The
      function of prolactin in mid-luteal phase was compared in pregnant and
      nonpregnant dogs. A dopamine agonist, cabergoline, known for its prolactin
      secretion inhibitory effects, was injected subcutaneously at a dose of 5
      micrograms/kg body weight in five pregnant and five nonpregnant Beagle bitches.
      Mean plasma prolactin and progesterone were dramatically suppressed for 4 to 5
      days after injection in both groups when compared with control pregnant and non
      pregnant animals, whereas no effect on luteinizing hormone (LH) secretion was
      observed. The decline in plasma progesterone occurred after that in prolactin,
      suggesting plasma progesterone was impaired by inhibition of prolactin secretion.
      These results confirm the luteotropic importance of prolactin in pregnant
      bitches, and also demonstrate its importance in luteal phase of the nonpregnant
      dog. Second, to demonstrate that the effects of cabergoline were mediated by
      prolactin inhibition and not by a direct action on the corpus luteum, concomitant
      administration on Day 30 of cabergoline and prolactin (375 micrograms i.v. twice
      daily on Days 30 and 31) or cabergoline and LH (750 micrograms i.v. twice daily
      on Days 30 and 31) was affected in two groups of five pregnant animals each.
      Results showed that only prolactin was able to reverse the negative effects of
      cabergoline on circulating progesterone. This confirms the indirect mode of
      action of the dopamine agonist, cabergoline on corpus luteum function. Third,
      further investigation on the precise luteotropic role of prolactin was made by IV
      injection of 375 micrograms pure canine prolactin twice daily in five pregnant
      bitches on Days 30 and 31, and in five pregnant bitches on Days 40 and 41. No
      direct stimulatory effect of prolactin on plasma progesterone secretion occurred.
      Nor was there a noticeable effect on plasma LH secretion. These results suggest
      that prolactin is unable to directly stimulate progesterone secretion by the
      corpus luteum of pregnancy. The results of this study suggest that prolactin is
      an essential luteotropin in the dog from mid-luteal phase in both pregnant and
      nonpregnant animals. However, it appears to act by sustaining corpus luteum
      lifespan and function rather than by direct stimulatory effects on progesterone
      secretion.

PMID- 8985669
TI  - Prolactin does not enhance glucose-stimulated insulin release in red deer stags.
AB  - Red deer stags have a seasonal pattern of insulin secretion that is characterized
      by both elevated basal and glucose-stimulated insulin release in summer compared
      with winter. Since the seasonal timing of this pattern is similar to that of
      prolactin and growth rate, the objectives of this study were: first, to determine
      whether prolactin is associated with the enhanced secretion of insulin during the
      summer growth period, and second, to determine whether a chronic reduction in
      plasma prolactin levels would alter body composition. Prolactin was suppressed in
      plasma using a long-acting form of the dopamine agonist bromocriptine (parlodel
      LA), which was administered at one of four doses (0-0.3 mg/kg) to each of four
      groups of castrate stags. Bromocriptine was administered during two 6-wk periods;
      the first in winter and the second in summer. During the sixth wk of each period,
      each animal was given three IVGTT at the following glucose doses (10 mg/kg, 70
      mg/kg, and 200 mg/kg). Two d later, ovine prolactin was administered to each
      animal (0.08 mg/kg) and a single IVGTT (70 mg/kg) was given 2 hr later. Body
      composition was determined by the tritriated water dilution method at the
      beginning and end of each 6-wk treatment. Chronic suppression of prolactin during
      winter or summer did not significantly alter the amount of insulin released after
      each IVGTT, nor did it significantly alter body composition. Furthermore, acute
      administration of prolactin did not significantly enhance the release of insulin
      following an IVGTT, during winter or summer treatment periods. It is concluded
      that elevated levels of prolactin in summer do not enhance the release of insulin
      to glucose in red deer. Furthermore, a reduction in growth rate following a
      reduction in plasma prolactin is not associated with a change in body
      composition.

PMID- 8985671
TI  - Type II fiber predominance with motor neuron dysfunction.
AB  - Several variations in the muscle fiber distribution and differentiation have been
      described. Different hypotheses, including maturational dysfunction of motor
      neurons have been postulated. We present a 28 year-old male with proximal
      weakness, and negative family history. Motor strength was 4-/5 proximally and
      4+/5 distally in the extremities. He was areflexic with trace triceps jerks.
      Electrophysiological studies showed motor neuron dysfunction. Marked type II
      fiber predominance 97% was noted without group atrophy on a vastus-lateralis
      muscle biopsy. Type 2A were the largest with type 2B and 2C smaller than type 1.
      A deltoid muscle biopsy and electrophysiological studies performed nine years
      earlier depicted the same changes. With electrophysiological studies consistent
      with static motor neuron dysfunction and clinical and pathological presentation
      of myopathy, we propose a functional abnormality of motor neuron in-utero leading
      to abnormal muscle fiber differentiation and growth.

PMID- 8985670
TI  - Plasma cortisol responses to remote adrenocorticotropic hormone (ACTH) infusion
      in free-ranging red deer (Cervus elaphus).
AB  - A remote infusion and blood collection device (Dracpac) was used on free-ranging
      red deer stags to deliver i.v. a range of ACTH1-24 doses and collect blood for
      cortisol determination. In Experiment 1, conducted in September, saline and 1, 4,
      and 16 IU ACTH/100 kg bodyweight were infused (n = 5-7 per treatment). In
      Experiment 2 (November), 16 and 64 IU ACTH/100 kg were infused (n = 5 per
      treatment); and the response of animals to restraint was also assessed (n = 6).
      Pre-infusion concentrations of plasma cortisol were low (mean 6.5 +/- 1.0 ng/ml),
      and unaffected by infusion of saline. ACTH significantly elevated plasma cortisol
      concentrations, with mean peak concentrations occurring 20-40 min postinfusion.
      Duration of the response was dose dependent, ranging from 80-160 min. With
      increasing doses of ACTH, maximal peak heights plateaued at approximately 40 and
      60 ng/ml in September and November, respectively; whereas the areas under the
      curves tended to increase. The minimum dose of ACTH that resulted in a maximal
      peak cortisol response was 4 IU. The maximum peak height of the cortisol response
      to 16 IU tended to be higher (P < 0.10) in November compared with September,
      suggesting that adrenal responsiveness may change over this period. The adrenal
      response to a 16-IU ACTH challenge in Experiment 2 resulted in similar plasma
      cortisol concentrations to an acute stress event (restraint). Four IU/100 kg ACTH
      i.v. is recommended as an appropriate dose for ACTH infusion studies in red deer
      stags. When used in conjunction with the Dracpac technique, it becomes a stress
      free, repeatable procedure for assessing aspects of adrenal cortex physiology in
      free-ranging deer.

PMID- 8985672
TI  - Auditory evoked potentials in postconcussive syndrome.
AB  - The neuropsychiatric sequelae of minor head trauma have been the source of
      controversy. Most clinical and imaging studies have shown no alteration after
      concussion, but neuropsychological and neuropathological abnormalities have been
      reported. Some changes in neurophysiologic diagnostic tests have been described
      in postconcussive syndrome. We recorded middle latency auditory evoked potentials
      (MLR) and slow vertex responses (SVR) in 20 individuals with prolonged cognitive
      difficulties, behavior changes, dizziness, and headache after concussion. MLR is
      utilized alternating polarity clicks presented monaurally at 70 dB SL at 4 per
      second, with 40 dB contralateral masking. Five hundred responses were recorded
      and replicated from Cz-A1 and Cz-A2, with 50 ms. analysis time and 20-1000 Hz
      filter band pass. SVRs were recorded with the same montage, but used rarefaction
      clicks, 0.5 Hz stimulus rate, 500 ms. analysis time, and 1-50 Hz filter band
      pass. Na and Pa MLR components were reduced in amplitude in postconcussion
      patients. Pa latency was significantly longer in patients than in controls. SVR
      amplitudes were longer in concussed individuals, but differences in latency and
      amplitude were not significant. These changes may reflect posttraumatic
      disturbance in presumed subcortical MLR generators, or in frontal or temporal
      cortical structures that modulate them. Middle and long-latency auditory evoked
      potentials may be helpful in the evaluation of postconcussive neuropsychiatric
      symptoms.

PMID- 8985673
TI  - Turn-amplitude analysis in neuromuscular diseases.
AB  - The first attempts in computer aided EMG analysis were performed for the
      automatic evaluation of interference pattern. In the routine work the turn
      amplitude analysis (T/A), introduced by Stalberg and Antoni (1981), proved to be
      an accurate and easily performed procedure, with the advantage of being
      relatively independent of force. The aim of our study was to determine the
      diagnostic significance of T/A analysis in various neuromuscular diseases. The
      recordings were performed with Madaus Amplaid EMG 15, and concentric needles were
      used. fifty subjects had been investigated. The diagnoses were based on clinical,
      biochemical and histological findings. Tibialis anterior, quadriceps femoris,
      extensor digitorum communis and biceps brachii muscles were regularly sampled. In
      myogenic conditions a distinct correlation was found between the severity of
      muscle damage and T/A values. The more pronounced abnormalities were observed in
      Duchenne boys. Except the ALS in neurogenic processes correlation was found
      between the severity of muscle damage and T/A analysis, too. The central lesions
      did not have any effect on the T/A results. Examples of the possible sources of
      technical errors were presented and comparisons to the traditional concentric
      needle EMG were done.

PMID- 8985674
TI  - Differential diagnosis of limb girdle syndromes.
AB  - The term limb girdle syndrome includes a variety of neuromuscular disorders like
      the scapulohumeral and pelvifemoral types of muscular dystrophy, quadriceps
      myopathy and Wohlfart-Kugelberg-Welander syndrome. There may be considerable
      difficulty in distinguishing between different types of limb girdle syndrome,
      even with the aid of electromyographic and muscle biopsy examinations. The aim of
      this investigation was to reestablish the clues for distinguishing between
      different types of limb girdle syndrome. Fifty-four patients with limb girdle
      syndromes took part in this investigation. They were subdivided into two groups
      according to EMG and muscle biopsy data. The first group consisted of 39 patients
      with limb-girdle type of muscular dystrophy and the second group consisted of 15
      patients with juvenile type of spinal muscular atrophy. Our results revealed that
      neurological examination was not enough to distinguish the different types of
      limb girdle syndrome. The most important electromyographic findings in patients
      with muscular atrophy are the neurogenic action potentials and fasciculations.
      Fibrillations, positive sharp waves and bizzare discharges may be found also in
      some patients with muscular dystrophy. Myogenic action potentials are found in
      some patients with muscular atrophy and so may cause confusion. Muscle biopsy may
      also reveal some myogenic features in patients with muscular atrophy. In
      conclusion electromyography and muscle biopsy are useful in the differentiation
      of different types of limb girdle syndrome, as well as, in determining the exact
      pattern of muscle involvement.

PMID- 8985675
TI  - Botulism with sensory symptoms diagnosed by neuromuscular transmission studies
      associated with edrophonium responsiveness.
AB  - A 43-year-old female patient developed bilateral ophtalmoplegia, bulbar paresis
      and weakness of the respiratory and extremity muscles. Additionally she had
      decreased sensation on the left half of the body. Repetitive nerve stimulation
      (RNS) test confirmed the diagnosis of botulism and edrophonium injection caused a
      reduction in the decremental response. When in doubt, RNS testing can provide the
      definitive results in the diagnosis of botulism.

PMID- 8985676
TI  - Somatosensory and visual evoked potentials study in young insulin-dependent
      diabetic patients.
AB  - To evaluate central nervous system involvement in diabetes, somatosensory (SEPs)
      and visual (VEPs) evoked potentials were investigated in a group of 35 patients
      and 20 sex, age-matched controls. In order to avoid methodological biases due to
      different type and duration of disease, we studied an omogeneous group of young
      insulin-dependent diabetics with ten or more year duration of disease. In our
      results VEP and SEP parameters were found abnormal in 10 (28%) patients, all of
      whom presenting clear signs of peripheral neuropathy. In diabetic patients median
      and tibial SEPs showed significant increase in absolute latency mean values of
      several components except interpeak intervals, as well as mean P 100 latencies
      were significantly increased in both eyes at 15' check size stimulation pattern.
      VEP and SEP components were not generally significantly associated with the
      indices of peripheral function. In contrast, in diabetics significant
      correlations were found between P 100 latencies and median SEP parameters
      including interpeak intervals. No major associations related VEP and SEP
      latencies to duration of diabetes and prevailing glycaemic control. In conclusion
      the central nervous system involvement in young insulin-dependent diabetics, even
      though diffusely present, seems unequivocally concomitant to peripheral
      conduction impairment.

PMID- 8985677
TI  - Cocontraction and phasic activity during GAIT in children with cerebral palsy.
AB  - Simultaneous activity of agonist and antagonistic muscles during a task is known
      as cocontraction. The primary aim of the present study was to use a cocontraction
      index (CI) to quantify differences in EMG activity between a group of CP and
      control children at two different walking speeds. The secondary aim was to
      compare the amount of time the muscles were activated ("on" thresholds) between
      the groups. Seventeen subjects volunteered for the study. One group consisted of
      9 (7M, 2F) children with CP (age 12.7 +/- 2.8 years, mean +/- SD). The second
      group consisted of 8 able-bodied controls (7M, 1F). The discontinuous submaximal
      treadmill walking protocol had two 4min stages at 0% gradient. Speeds selected
      were 3 km.h-1 and 90% of the pre-determined fastest walking speed (FWS). Two
      sites of CI were measured from the EMGs of tibialis anterior and soleus (leg) and
      vastus lateralis and hamstrings (thigh). Significantly (p < 0.05) higher CI
      values were noted for the CP subjects compared to the controls, irrespective of
      speed or cocontraction site and there was a significant (p < 0.05) increase in CI
      values with increased walking speed for both CP and control subjects. Phasic
      analyses for 5% max EMG and 10% max EMG "on" thresholds demonstrated significant
      (p < 0.05) main effects for group (CP subjects had a longer time period of muscle
      activation than controls) and speed (muscles were active longer at 90% FWS than 3
      km.h-1). The precise mechanisms by which cocontraction contributes toward
      abnormal gait and wasted mechanical energy require further research incorporating
      both electromyographic and kinematic analysis.

PMID- 8985678
TI  - Variation of reaction time can be reduced by the time locked application of
      magnetic stimulation of the motor cortex.
AB  - It was the aim of this study to determine the influence of non-invasive magnetic
      stimulation on the performance of a visually induced reaction task. The
      experiment was performed in 8 healthy volunteers. After a visual stimulus
      subjects had to move their thumbs as soon as possible. The muscular reaction was
      recorded with surface EMG on both sides. After the visual go-signal a magnetic
      stimulus (Fig. 8 coil) was applied above the right or left motor cortex at
      varying time intervals (30 and 110 ms). The magnetic stimulus was randomly given
      or not. Short time intervals between visual and magnetic stimulus induced a
      shortening, long intervals induced a prolongation of the reaction time. The
      contralateral reaction time was always longer than the ipsilateral one. Compared
      with the reaction times without magnetic stimulation, the intraindividual
      standard deviation of the reaction times was markedly reduced by the application
      of the magnetic stimulation. This reduction was greater in ipsilateral than in
      contralateral recordings. The kind of the instruction had additional modifying
      effects.

PMID- 8985679
TI  - The importance of paraspinal muscle EMG in cervical and lumbosacral
      radiculopathy: review of 100 cases.
AB  - It is well known that examination of the paraspinal muscles are an important part
      of the electrodiagnostic (EDX) evaluation of a patient with suspected
      radiculopathy. However, many electromyographers hesitate to routinely include
      this in their study. A random retrospective chart review was performed on 49
      patients with cervical radiculopathy and 51 patients with lumbosacral
      radiculopathy to determine the frequency of EDX abnormalities in the paraspinal
      muscles and limb muscles. Criteria for abnormality was the presence of
      spontaneous activity in two muscles in a myotomal pattern in the limb, or in the
      paraspinal muscles. It was found that 20 out of 49 (40.8%) of the cervical
      radiculopathies and 10 out of 51 (19.6%) of the lumbosacral radiculopathies had
      abnormalities restricted only to the paraspinal muscles. These results indicate
      that especially in the cervical spine, a significant percentage of patients with
      radiculopathy will be missed if examination of the paraspinal muscles are not
      part of the EDX evaluation of the patient with suspected radiculopathy.

PMID- 8985680
TI  - Effects of physiotherapy on F-wave-amplitudes in spasticity.
AB  - F-wave amplitudes have been used to demonstrate changes of motor neuron
      excitability in spasticity and pharmacological antispastic therapy. In this study
      it is shown that F-wave amplitudes can also be used to document changes of motor
      neuron excitability as an effect of physiotherapy. Ten F-waves were recorded
      immediately before and after physiotherapy in 42 legs of 21 patients with spastic
      paraparesis due to multiple sclerosis. Mean F-wave amplitude, maximum F-wave
      amplitude, mean F-wave/M-response ratio and maximum F-wave/M-response ratio were
      significantly lower after physiotherapy than before. Therefore the antispastic
      effect of physiotherapy is documented by a decrease of F-wave-amplitude
      parameters.

PMID- 8985681
TI  - Developmental and seizure-related regional differences in immediate early gene
      expression and GABAergic abnormalities in the brain of EL mice.
AB  - To examine the hypothesized role of the immediate early gene (IEG) response in
      synaptic plasticity and in epileptogenesis, we studied the spatial specificity of
      the expression of IEG in EL mice, a well known mutant model of epilepsy. Also to
      examine the 'GABA hypothesis' in epilepsy, GABA concentration and GAD activity
      was determined in micro brain regions (10-300 ng) of EL mice related to the focus
      in the parietal cortex and the hippocampus. We found that the IEG expression
      after seizures is not related to the seizure pattern, but to the seizure history,
      seizure threshold and development of EL[s]. Even in the interictal period, EL
      mice with long seizure histories and very low seizure thresholds demonstrate IEG
      expression continuously. This is probably strengthened by repeated seizures. The
      IEG expression site is however located in the hippocampal CA1, which is the final
      terminal of various inputs from other areas of the limbic system. It is proposed
      that the continuous expression of IEGs might play a different role from that of
      transiently expressed IEGs. Developmentally, the site of IEG expression shifted
      from one site to another in a very similar manner as in the IEG expression with
      propagation of paroxysmal discharges in each seizure, and the three-dimensional
      expression area was gradually expanded, suggesting a change in the regional
      active site during epileptogenesis. These lines of evidence suggest that during
      development as well as repetitive seizures, frequent expressions of IEGs and
      syntheses of Fos and Zif proteins might facilitate synaptic conductivity involved
      in epileptogenesis. The sites of abnormal GABA concentrations and GAD activities
      were almost the same in the parietal cortex, around Sidman atlas coronal section
      No. 300 and in the hippocampal CA1 pyramidal cells as the spatio-temporal
      specific IEG expression sites. These findings strongly suggest that IEG
      expression and abnormal GABAergic functions are involved in epileptogenesis in EL
      mice.

PMID- 8985682
TI  - Analysis of the kinetics of synaptic inhibition points to a reduction in GABA
      release in area CA1 of the genetically epileptic mouse, El.
AB  - In order to determine whether changes in synaptic inhibition are involved in
      chronic models of epilepsy, it is necessary to understand the factors which
      determine the kinetics of fast gamma-aminobutyric acid (GABA)ergic inhibition.
      For this purpose, we analyzed the decaying phase of isolated inhibitory
      postsynaptic currents (IPSC) in rats CA1 pyramidal cells. Reduction of GABA
      release (by reducing [Ca2+]o or paired-pulse stimulation) or blockade of GABA
      uptake (with tiagabine) led to the conclusion that small changes in the amount of
      GABA available for postsynaptic binding have little effect on the peak amplitude,
      but have marked effect on the duration of the IPSC. We then studied isolated
      GABAA receptor-mediated inhibition in area CA1 of the El mouse strain, which is
      genetically predisposed to epilepsy. Results were compared with the non
      epileptogenic mother strain, ddY. Inhibitory postsynaptic potentials (IPSPs) in
      El mice (IPSPEl) were not significantly different in amplitude of those from ddY
      mice (IPSPddY). However, the rise-time and duration of IPSPEl were respectively
      about 25% and 50% shorter than those of IPSPddY. With appropriate pharmacological
      manipulation of GABA release or uptake, IPSPEl could be made to resemble the
      IPSPddY and vice versa. It is concluded that the synaptic release of GABA in area
      CA1 of the El mouse is decreased compared to that of the ddY mouse.

PMID- 8985683
TI  - Anticonvulsant effect of reduced NMDA receptor expression in audiogenic DBA/2
      mice.
AB  - Pretreatment of DBA/2 mice (n = 14-15 per group) with an 18-mer antisense probe
      to the NMDA-receptor submit NR1 (2 x 1 micrograms, or 2 x 83 pmol, NR1 antisense
      probe intracerebroventricularly, -29 and -7 h before testing for seizure
      response) resulted in almost complete suppression of sound-induced clonic
      seizures. A saline-treated group gave a 100% seizures response, while the group
      treated with NR1 antisense probe gave a 7% seizure response to the sound
      stimulus. The group treated with NR1 nonsense-probe showed no anticonvulsant
      protection (93% seizure response). The anticonvulsant protection observed
      following NR1 antisense administration was of relatively short duration, with
      seizure response gradually returning to control levels 12 to 24 h following the
      termination of antisense administration. When NR1 receptor levels were assessed
      by receptor autoradiography ([3H]-MK 801 and -CGP 39653 binding) in the same
      groups of mice, significant (20%) reductions in NR1 levels were observed in the
      retrosplenial cortex and the overall cortex. The seizure-induced expression of c
      fos and NGFI-A in thalamus, hypothalamus, inferior colliculus and medical
      geniculate seen in vehicle- and NR1 nonsense-treated mice was completely blocked
      by NR1 antisense pretreatment.

PMID- 8985684
TI  - Cortical versus thalamic mechanisms underlying spike and wave discharges in
      GAERS.
AB  - Genetic absence epilepsy rats from Strasbourg (GAERS) have non-convulsive
      generalized seizures associated with spike-wave (SW) discharges, which are due to
      a hyperexcitable state of the thalamo-cortico circuits involving the reticular
      thalamic nucleus (nRt). Investigation of the primary genetically-determined
      defect responsible for GAERS epilepsy revealed the following abnormalities: (1)
      increased effectiveness of AMPA receptors dependent glutamate-mediated
      transmission; (2) impairment of GABA-mediated transmission in the neocortex; (3)
      increased amplitude of the voltage-dependent low-threshold Ca2(+)-current (I(T))
      in the nRt. The maturational profile of these abnormalities supports the
      conclusion that the abnormality in the I(T) current in the nRt is the primary
      genetically-determined defect, which may secondarily induce the other changes
      found in the neocortex and thalamus of GAERS.

PMID- 8985685
TI  - No loss in total neuron number in the thalamic reticular nucleus and neocortex in
      the genetic absence epilepsy rats from Strasbourg.
AB  - The thalamic reticular nucleus (nRt) as well as the neocortex are involved in the
      bilateral spike- and wave-discharge loop in genetic absence epilepsy rats from
      Strasbourg (GAERS). Neuron loss in different brain areas has been described in
      relation to epilepsy with convulsive seizures. We have previously investigated
      the ventrolateral/posterior nucleus of thalamus in GAERS and found no neuron
      loss. We applied the same efficient and unbiased stereological methods to nRt and
      to neocortex and again found no loss of neurons. The oscillatory properties of
      nRt are not related to neurons loss.

PMID- 8985686
TI  - Neuronal migration disorders and epilepsy: a morphological analysis of three
      surgically treated patients.
AB  - Despite the increasing number of patients affected by neuronal migration
      disorders (NMDs) recently diagnosed in vivo by means of magnetic resonance
      imaging (MRI), few detailed data on the correlation between the neuroradiological
      and the anatomical features in the single NMD case are available. The present
      paper reports a combined cytoarchitectural and immunocytochemical analysis, by
      means of antisera recognizing specific neuronal and glial markers, of three MRI
      diagnosed NMD patients surgically treated for the relief of intractable seizures.
      The first case was a giant subcortical nodular heterotopia of morphologically
      normal neurons lacking any type of cortical lamination. The second case was a
      layered polymicrogyria with an abnormal amount of ectopic neurons in the
      underlying white matter. The third case was a focal cortical dysplasia
      characterized by a dramatic disruption of the normal cortical layering associated
      with marked cytological abnormalities. The present data demonstrate that the
      macroscopical and microscopical brain abnormalities can be markedly different in
      different NMD subtypes, and suggest that different anatomical substrates can
      underlie the intrinsic hyperexcitability of these brain malformations. The
      relevance of further prospective clinico-morphological studies for a better
      understanding of the mechanisms determining the development of these brain
      malformations is underlined.

PMID- 8985688
TI  - Characterization of neuronal migration disorders in neocortical structures: I.
      Expression of epileptiform activity in an animal model.
AB  - Hypoxia, ischemia and other forms of brain injury during the pre- and perinatal
      period may cause neuronal migration disorders which results in irreversible
      structural modifications. In human neocortex, these malformations have been
      associated with severe mental retardation, motor dysfunction and the
      manifestation of therapy-resistant epilepsy. We were interested in analyzing the
      expression of epileptiform activity in an animal model of neocortical migration
      disorders. Newborn rats received a focal freeze lesion and were investigated
      anatomically and in vitro electrophysiologically after survival times of up to
      five months. Anatomic abnormalities included loss of normal cortical lamination
      (focal microgyrus) and presence of ectopic cell clusters in layer I and in the
      white matter (heterotopia). The functional in vitro analyses with eight
      extracellular recording electrodes revealed a prominent hyperexcitability of the
      disorganized neocortical network. Electrical stimulation of the afferents
      elicited epileptiform responses that propagated over > 4 mm in the horizontal
      direction. In untreated and sham-operated animals, this spread of evoked activity
      was restricted to 0.5-1 mm. Epileptiform responses were not significantly
      affected by APV but blocked by NBQX, indicating that AMPA receptors play a
      prominent role in the generation and propagation of this pathophysiological
      activity. Our data suggest that the experimentally induced migration disturbances
      cause long-term structural and/or functional modifications in the neocortical
      network which may form the basis for the expression of epileptiform activity.

PMID- 8985687
TI  - Review of the role of inhibitory neurons in chronic epileptic foci induced by
      intracerebral tetanus toxin.
AB  - Blocking inhibition provides one of the most common experimental means of
      triggering epileptic activity in hippocampus and neocortex. However, it has
      proved much more difficult to show that chronic models of epilepsies are due to
      disinhibition. One problem is knowing how much inhibition needs to be blocked to
      provide a sufficient mechanism for epileptic activity. We have found that
      inhibitory (GABAA) transmission, estimated from evoked monosynaptic IPSCs, must
      be reduced to 17% of their control amplitude (by 4-7 microM bicuculline) before
      hippocampal slices generate all-or-none epileptic discharges. Similar estimates
      of inhibition in chronic epileptic foci induced by intrahippocampal injection of
      tetanus toxin showed that monosynaptic IPSCs dropped to 10% of control in the
      injected hippocampus during the first 2 weeks after injection. At all other
      stages of the active epileptic foci in the two hippocampi the reduction in IPSCs
      was not alone sufficient for epileptic activity; at 4-6 weeks IPSCs were normal
      despite continued epileptic activity. One likely mechanism for the late epileptic
      activity is a reduction of either the intrinsic excitability, or the synaptic
      excitation, of inhibitory interneurons so they fail to be recruited normally.
      Alternative mechanisms include the formation of new excitatory connections, as
      found at modest levels in the dentate gyrus. Several mechanisms may play a part
      in chronic foci such as those induced by tetanus toxin, either acting together,
      or sequentially during the progression of the epileptic focus.

PMID- 8985689
TI  - Epileptiform activity in the piriform cortex of the in vitro isolated guinea pig
      brain preparation.
AB  - Brief intracerebral injections of bicuculline in the anterior portion of the
      piriform cortex of the isolated guinea pig brain preparation induce a transient,
      localized disinhibition confined to the site of drug application. The
      epileptiform activity generated at the bicuculline focus propagates and induces
      secondary excitability changes in remote cortical regions within the olfactory
      lobe. Long lasting changes in synaptic potentials were observed in the posterior
      piriform cortex, where long-projective cortico-cortical fibers originating from
      the site of bicuculline injection terminate. The activation of rhythmic,
      transient afterdischarges at the bicuculline focus was critical for the
      development of persistent 'epileptiform' associative synaptic potentials in
      remote cortical regions. When transient afterdischarges were prevented,
      epileptiform associative potentials in the posterior piriform cortex appeared
      only transiently and vanished within 20 min. The persistent secondary changes in
      synaptic excitability that occur in cortical regions distant from the acutely
      induced primary epileptic focus may represent one of the transition mechanisms
      toward chronic epileptogenesis.

PMID- 8985690
TI  - Brain injury-induced enhanced limbic epileptogenesis: anatomical and
      physiological parallels to an animal model of temporal lobe epilepsy.
AB  - Traumatic brain injury (TBI) is a leading cause of symptomatic epilepsy in young
      adults. This study examined physiological and anatomical epileptogenic
      consequences of a prior incident of TBI in rats. Rats were subjected to a fluid
      percussion brain injury one week prior to experimentation, and in vitro
      electrophysiological recording studies were conducted using combined hippocampal
      entorhinal cortical slices (HEC slices). Results were compared to sham operated
      controls and rats in which a condition of chronic temporal lobe epilepsy was
      induced by a 2 h bout of pilocarpine-induced status epilepticus 2 months prior to
      recording (PILO). In field potential recording, PILO HEC slices evidenced a
      greater degree of disinhibition in Ca1 than did TBI or control slices. TBI slices
      showed greater disinhibition in the dentate gyrus than did PILO or control rats.
      In in vitro kindling experiments, 86% of TBI HEC slices generated self-sustaining
      epileptic activity within 9 stimulus trains. This type of activity was never
      triggered in control slices. HEC slices prepared from PILO animals generated self
      sustaining epileptic activity with fewer stimulus trains than did TBI slices. In
      anatomical studies, both TBI and PILO hippocampi evidenced significant loss of
      neurons within the hilar region. TBI induces a series of changes within the
      limbic system of rats, which are qualitatively similar in many aspects but
      quantitatively less severe than changes seen in rats with chronic temporal lobe
      epilepsy. These physiological and anatomical TBI-associated alterations in the
      limbic system may contribute to the development of epilepsy following head
      trauma.

PMID- 8985691
TI  - The model of pentylenetetrazol-induced status epilepticus in the immature rat:
      short- and long-term effects.
AB  - In order to assess acute, short and long-term effects of seizures in the immature
      rat brain, we studied the metabolic, circulatory and histopathological changes
      induced by pentylenetetrazol (PTZ) given at postnatal day 10 (P10) or 21 (P21).
      Seizures were induced by repetitive subconvulsive injections of PTZ given as a
      first dose of 40 mg/kg followed 10 min later by 20 mg/kg. Thereafter, rats
      received every 10 min additional injections of PTZ 10 mg/kg until the onset of
      status epilepticus. Local cerebral metabolic rates for glucose (LCMRglc) were
      measured both during the seizures in P10 and P21 rats and in the young adult
      animal at P60 by means of the quantitative 2-deoxyglucose technique. Rates of
      local cerebral blood flow (LCBF) were determined during the seizures by the
      iodoantipyrine technique. Short-term histological changes were assessed by acid
      fuchsin and hematoxylin-eosin staining and by HSP72 immunohistochemistry. At P10,
      LCMRglcs uniformly increased (38-400%) over control values during seizures. At
      P21, metabolic increases (39-181%) occurred only in 20% of the structures while
      LCMRglcs decreased in most cortical, hippocampal and sensory areas as well as in
      mammillary body, discrete thalamic nuclei and white matter areas. At P10, LCBF
      rose (32-184%) in all brain structures whereas, at P21, LCBF decreased in
      cortical, hippocampal and sensory regions and increased in most other areas. At
      P60, in animals having seized at either age, significant long-term decreases in
      LCMRglcs were recorded in hippocampus, auditory and piriform cortex, medial
      geniculate body and mammillary body. In P60 animals exposed to PTZ at P10,
      LCMRglcs were also decreased in 3 other sensory areas. In P60 animals exposed to
      seizures at P21, LCMRglcs were additionally decreased in sensory regions,
      cortices, thalamic and hypothalamic regions. Neuronal cells were transiently
      stained with acid fuchsin, with a peak occurring at 24 h after the seizures. The
      stain was visible in all regions of cerebral cortex and hippocampus and in some
      thalamic and hypothalamic nuclei. This transient staining was not accompanied by
      cell degeneration as assessed by hematoxylin-eosin histology. No HSP72 expression
      could be detected 24 h after the seizures, neither at P10 nor at P21. The present
      study shows that the immature rat neurons undergo altered metabolic rates and
      local circulatory decreases in the acute phase, a change in the affinity of acid
      fuchsin as a short-term effect and long-term metabolic decreases. All these
      changes are located in the same regions, i.e., cerebral cortex, hippocampus,
      sensory regions as well as scattered thalamic and hypothalamic nuclei. Thus,
      short- and long-term metabolic changes induced by seizures can be used as an
      index of cell stress in the immature rat brain. Since all these changes occur in
      the absence of visible neuronal death, they might be related to changes in the
      final arborization and synaptic organization of the developing brain.

PMID- 8985692
TI  - Pentylenetetrazol-induced kindling: early involvement of excitatory and
      inhibitory systems.
AB  - Alterations in the brain of rats receiving a single non-convulsive administration
      pentylenetetrazol (PTZ), 30 mig/kg, i.p. (single PTZ group) were investigated and
      compared with those detected in fully PTZ kindled rats (chronic PTZ group). In
      vitro receptor autoradiography experiments showed that both single and chronic
      PTZ groups presented mu opioid and benzodiazepine (BDZ) receptor binding in
      specific brain areas. Using an antibody generated against the delta opioid
      receptor (DOR-1), it was found that DOR-1 like immunoreactivity was reduced in
      cortex and amygdala in mice following single and chronic PTZ administration.
      Microdialysis experiments revealed that the administration of PTZ 30 mg/kg, i.p.
      in freely moving rats without previous experience with the drug, induces a rise
      in glutamate release, detected in the first and second 10 min dialysates
      collected from amygdala (138% and 50%, respectively) and frontal cortex (70% and
      45%, respectively) as well as aspartate in frontal cortex in the first and second
      PTZ-dialysates (143% and 80%, respectively). Subsequently, values returned to
      basal conditions. It may be speculated that decreased BDZ receptor binding
      results from enhanced release of GABA. On the other hand, the decrease of mu
      receptor binding and DOR-1 immunoreactivity observed after PTZ administration may
      be the result of enhanced levels of opioid peptides probably released over the
      kindling procedure. In conclusion, the present study indicates that PTZ-kindling
      is associated with an imbalance between excitatory and inhibitory systems which
      is apparent early in the epileptogenic process.

PMID- 8985693
TI  - Developmental aspects of the pilocarpine model of epilepsy.
AB  - Prolonged seizures in young children may precede the later development of focal
      or generalized seizures. To study the age-related susceptibility to the
      development of chronic epilepsy we used the pilocarpine model of epilepsy (PME).
      This model is well characterized in adult rats, and presents three distinct
      periods: (a) an acute period of status epilepticus (SE), (b) a silent period of a
      progressive normalization of EEG and behavior, (c) a chronic period of
      spontaneous recurrent seizures. Wistar rats aged 7-120 days received pilocarpine
      hydrochloride (170-380 mg/kg, i.p., according to age), 30 min after
      methylscopolamine (1 mg/kg, s.c.). All surviving animals were observed for 120
      days. The results indicate that chronic seizures following pilocarpine-induced
      status epilepticus can be induced in rats if the status is induced after the 18th
      day of life. The age-related differences in the susceptibility of young rats to
      developed chronic epilepsy reflect the complexity of seizure activity in immature
      brain and provide for an apparent distinction between the mechanisms of
      epileptogenesis in the mature and developing nervous system.

PMID- 8985694
TI  - Spontaneous seizures preferentially injure interneurons in the pilocarpine model
      of chronic spontaneous seizures.
AB  - It is still a question of much debate whether single epileptic seizures can cause
      cell loss. Despite the clinical impression that epilepsy in general is a
      progressive disorder, experimental evidence is not conclusive on this point.
      Recently, it has been shown that electrically-induced afterdischarges of less
      than 2 min may induce structural impairments in neurons. Here we evaluated
      whether spontaneous seizures would lead to similar impairments. Chronic
      spontaneous recurrent seizures were induced with pilocarpine (320 mg/kg, i.p.).
      Animals were sacrificed from 1 to 6 h either after single or multiple seizures. A
      Golgi-like sensitive silver-impregnation procedure was used to reveal injured
      neurons. Silver-impregnated dark neurons were never found in control animals nor
      in epileptic animals that had no behavioral seizures in the 8 h prior to
      sacrifice. After spontaneous seizures (injured) dark neurons were mostly
      interneurons and were present in hippocampus (CA1 stratum radiatum), amygdala,
      piriform cortex and other limbic structures. Animals with multiple seizures had a
      higher number of dark cells than animals with single seizures. Our findings
      suggest that even single generalized spontaneous tonic-clonic seizures can induce
      long-lasting morphological changes. Our results favor the idea that epilepsy is a
      progressive disorder where one seizure begets the next.

PMID- 8985695
TI  - Hypoxia-induced hyperexcitability in vivo and in vitro in the immature
      hippocampus.
AB  - Hypoxia is the most common cause of neonatal seizures and encephalopathy. We have
      previously developed an in vivo experimental model of perinatal hypoxia which
      exhibits age-dependent acute and chronic epileptogenic effects. Between postnatal
      day (P) 10-12, the rat exhibits acute seizure activity during global hypoxia,
      while no seizures are induced at earlier (P5) or older (P60) ages. Rats exposed
      to hypoxia between P10-12 have reduced seizure thresholds to chemical convulsants
      in adulthood. The nonNMDA antagonists NBQX appears to suppress both the acute and
      long term epileptogenic effects of hypoxia. The age-dependency of the
      hyperexcitable response to hypoxia in vivo can be reproduced in vitro using
      hippocampal slices. In Mg(2+)-free media, hypoxia induced ictal discharges within
      60 s of onset in 79% of slices from normal P10 rat pups compared to 11% of adult
      slices (p < 0.001). Model systems such as that described here allow for
      correlation of in vitro and in vivo electrophysiology and should provide data
      regarding the pharmacological and physiological characteristics of hypoxia
      induced seizure activity in the immature brain which could ultimately be applied
      to therapeutic strategies.

PMID- 8985696
TI  - Introduction to temporal lobe epilepsy.
AB  - Epileptic disorders are classified as idiopathic when they are genetically
      transmitted conditions that consist of epilepsy only, with no structural lesions
      in the brain and no associated neurological deficits, and symptomatic when they
      result from some other primary brain lesion or insult. Symptomatic temporal lobe
      epilepsy can be further divided into mesial temporal lobe epilepsy (MTLE), the
      condition associated with hippocampal sclerosis; lesional temporal lobe epilepsy
      due to specific identifiable lesions localized to areas that preferentially
      project to mesial temporal structures; and cryptogenic temporal lobe epilepsy,
      for which no etiology can be determined. Intensive clinical and basic research on
      MTLE, perhaps the most common form of human epilepsy, is currently being carried
      out in epilepsy research centers, and a number of experimental animals models
      have been developed to help elucidate the pathophysiology of this condition.
      Animal models are also important for determining how specific lesions induce
      epileptogenicity, and whether the neuronal mechanisms in mesial temporal lobe
      limbic structures are the same as those in neocortex. Cryptogenic temporal lobe
      epilepsy remains a major clinical challenge, and much more information needs to
      be derived from research on patients before relevant experimental animal models
      can be created.

PMID- 8985697
TI  - The pathogenic and progressive features of chronic human hippocampal epilepsy.
AB  - To design useful experimental models of epilepsy, it is necessary to clearly
      understand the known clinical-pathologic features of the disease process. Studies
      of mesial temporal lobe epilepsy (MTLE) patients have identified several
      distinctive clinical and pathophysiologic characteristics and many of these can
      be analyzed in experimental models. For example, patients with typical MTLE have
      medical histories that often contain an initial precipitating injury (IPI), are
      likely to have hippocampal sclerosis in the surgical specimen, and have better
      seizure outcomes than patients with typical idiopathic temporal seizures (i.e.
      cryptogenic). Hippocampal from children as young as age 1 year with IPI histories
      also demonstrate neuron damage similar to adults with hippocampal sclerosis.
      Compared to IPI patients without seizures (i.e. trauma, hypoxia, etc.), IPI cases
      with severe seizures showed younger ages at the IPI, shorter latent periods, and
      longer durations of habitual MTLE. Hippocampal damage is often bilateral,
      however, the epileptogenic side shows hippocampal sclerosis and the opposite side
      usually shows only mild neuron losses. Moreover, MTLE patients show declines in
      hippocampal neuron densities with very long histories of habitual seizures (15 to
      20 years), however, the additional neuron loss adds to the template of
      hippocampal sclerosis and occurs in limited subfields (granule cells, CA1 and
      prosubiculum). Hippocampal axon and synaptic reorganization is another pathologic
      feature of MTLE, and involves granule cell mossy fibers and axons immunoreactive
      for neuropeptide upsilon, somatostatin, and glutamate decarboxylase (which
      synthesizes GABA). Finally, MTLE patients with hippocampal sclerosis show
      increased granule cell mRNA levels for brain derived neurotropic factor, nerve
      growth factor, and neurotrophin-3 that correlate with mossy fiber sprouting or
      with declines in Ammon's horn neuron densities. Taken together, our data support
      the following concepts: (1) The pathogenesis of MTLE is associated with IPI
      histories that probably injure the hippocampus at some time prior to habitual
      seizure onsets, (2) most of the damage seems to occur with the IPI, (3) there can
      be additional neuron loss associated with long histories, (4) another pathologic
      feature of MTLE is axon reorganization of surviving fascia dentata and
      hippocampal neurons, and (5) reorganized axon circuits probably contribute to
      seizure or propagation.

PMID- 8985698
TI  - Astrocytes in kindling: relevance to epileptogenesis.
AB  - Astrogliosis is a prominent feature of epileptic foci, and may play a causal role
      in the development of seizures and the persistance of seizure disorders. We have
      studied morphological changes in astrocytes with respect to the evolution of
      seizures using the kindling model of epilepsy. Kindling-induced seizures result
      in a prominent hypertrophy of astrocytes that is accompanied by a reorganization
      of astrocytic cytoskeleton. The change in the morphology of astrocytes appears to
      be seizure-intensity dependent, occurs early in the kindling process, and
      persists for weeks following the last seizure. In addition to hypertrophy, we
      have observed an increase in proliferation of astrocytes in hippocampus, amygdala
      and piriform cortex, but no change in the expression of connexin-43 following
      kindling. Significantly, induction of a localized astrocyte hypertrophy prior to
      initiation of kindling does not result in seizures and does not facilitate
      kindling. Altogether these data suggest that 'gliosis' is an adaptive response to
      seizures.

PMID- 8985699
TI  - Neuroethological and morphological (Neo-Timm staining) correlates of limbic
      recruitment during the development of audiogenic kindling in seizure susceptible
      Wistar rats.
AB  - Acute audiogenic seizures are a model of generalized tonic-clonic seizures,
      induced by high intensity acoustic stimulation in genetically susceptible
      rodents. The neural substrate are sensory motor brainstem nuclei. Recruitment of
      forebrain structures takes places upon repetition of acoustically evoked
      seizures. The term audiogenic kindling means forebrain kindling evoked by
      repeated brainstem seizures and has been described in several strains of
      genetically epilepsy-prone rats. Thus, the present work was conducted in order to
      test the hypothesis that audiogenic kindling recruits the forebrain, which may be
      behaviorally evaluated and associated with morphological changes as well. The
      behavioral sequences observed during the development of audiogenic kindling were
      assessed by neuroethological methods (cluster analysis), with the ETHOMATIC
      program. Seizure severity indexes (brainstem and limbic seizures) and latencies
      of wild running and tonic-clonic seizures were measured to quantify seizure
      evolution. Densitometric analysis of Neo-Timm staining was used for assessing
      morphological changes associated with audiogenic kindling. In group I, II
      resistant (R) and 16 susceptible (S) animals were stimulated (120 dB) 21 times,
      and allowed a 10 day recovery period prior to retesting. In group II, 22 R and 20
      S were stimulated 60 times, and allowed a 2 month recovery period prior to
      retesting. Repetition of the acoustic stimulation in group I and group II
      susceptible animals led to a progressive and statistically significant
      attenuation of the behaviors associated with brainstem seizures and a concomitant
      increased expression of the behaviors associated with limbic seizures. After
      either a 10 day (group I) or 2 month (group II) recovery period, acoustic
      stimulation preferentially evoked brainstem-associated behaviors and seizures
      rather than limbic ones in the audiogenic susceptible animals, although in some
      animals overlapped brainstem and limbic seizures were detected. Latencies for the
      wild running and tonic seizures after acoustic stimulation significantly
      increased during audiogenic kindling for both group I and group II susceptible
      animals. The quantitative ethological evaluation in both group I and group II,
      illustrated by flowcharts, showed the evolution of the kindling installation by
      the presence of limbic seizure clusters, competing in time with the original
      tonic-clonic clusters. Expression of limbic seizures by group I animals, after
      acoustic stimulation, was not associated with changes in the mossy fiber Neo-Timm
      staining pattern of these animals. In group II however, Neo-Timm staining
      revealed mossy fiber sprouting in the ventral hippocampus (but not in the
      dorsal), and a significant change in the optical density of amygdaloid nuclei and
      perirhinal cortex in susceptible animals as compared to resistant ones. In
      conclusion, audiogenic kindling effectively recruits forebrain structures,
      responsible for the appearance of limbic seizures. It is possible that the
      paradigm used in group I was subthreshold for the development of clear-cut
      synaptic reorganization in the hippocampal mossy fiber system, since the
      behavioral patterns reverted ten days after the last seizure induction. In group
      II, however, an increased number of evoked seizures and a more prolonged time
      after the last chronic seizure showed structural re-arrangements in amygdala,
      perirhinal cortex and hippocampus, associated with permanence in terms of
      behavioral data (lack of regression of limbic seizures to control values).

PMID- 8985700
TI  - Glutamate AMPA receptors in the fascia dentata of human and kainate rat
      hippocampal epilepsy.
AB  - The present study examined the relationship between the patterns and densities of
      glutamate AMPA receptor sub-units GluR1 and GluR2/3 in the molecular layer of the
      fascia dentata and aberrant mossy fiber neoinnervation in human and kainate rat
      hippocampal epilepsy. Because AMPA sub-units modulate the fast glutamate synaptic
      transmission, we hypothesized that the AMPA receptor densities would be related
      to the glutamate-secreting mossy fibers, which could then contribute to seizure
      generation. In human hippocampal epilepsy, we found that the immunocytochemical
      labeling of GluR1 and GluR2/3 dendrites was positively related to the densities
      and spatial locations of the densest, aberrant neo-Timm stained supragranular
      mossy fibers. We used quantitative densitometry for the mossy fibers. However,
      the relatively faint and punctate immunocytochemical staining of the receptors
      did not allow true quantitative densitometry of the dendritic trees because in
      human epilepsy granule cell densities were decreased on average 50% of normal.
      Nevertheless, visual observations did confirm spatial relations between dense
      fascia dentata inner molecular layer mossy fibers and dense AMPA receptor
      staining. In the outer molecular layer, the mossy fibers were present only in the
      lower portion, were not densely-stained, and the AMPA receptors were only faintly
      labeled. Nevertheless, outer molecular layer AMPA receptor densities were usually
      present more distally than were the mossy fibers. Experiments were done using
      intrahippocampal kainate epileptic rats to test the time courses for the changes
      in mossy fibers and AMPA receptors. The upregulation of inner and outer molecular
      layer AMPA receptors occurred maximally within 5 days post-kainate injection,
      prior to any mossy fiber supragranular ingrowth. One hundred and eighty days
      after ipsilateral kainate the AMPA receptors were increased bilaterally in the
      inner and outer molecular layers despite the fact that the contralateral aberrant
      supragranular mossy fibers were minor in comparison to the dense ipsilateral
      mossy fiber hyperinnervation. These results suggest that in hippocampal epilepsy
      AMPA receptor numbers increase throughout the length of the molecular layer
      dendrites; however the AMPA receptor densities are greater in rough relation to
      the greatest aberrant mossy fiber presynaptic inputs. Interestingly, the receptor
      upregulation precedes the mossy fiber ingrowth and may play a role in initiating
      axonal sprouting or in maintaining the aberrant mossy fiber synapses.

PMID- 8985701
TI  - Vulnerability and plasticity of the GABA system in the pilocarpine model of
      spontaneous recurrent seizures.
AB  - Several similarities exist between the alterations observed in the chronic
      pilocarpine model of recurrent seizures in the rat and those found in human
      temporal lobe epilepsy. The present studies are focused on changes in the GABA
      system in this model. Following the initial pilocarpine-induced seizures, a
      substantial loss of glutamic acid decarboxylase (GAD) mRNA-containing neurons has
      been found in the hilus of the dentate gyrus (Obenaus et al., J. Neurosci., 13
      (1993) 4470-4485), and, recently, a loss of GAD mRNA-labeled neurons has also
      been found in stratum oriens of CA1. Yet numerous other GABA neurons remain
      within the hippocampal formation, and there appear to be multiple compensatory
      changes in these neurons. Labeling for GAD65 mRNA and associated protein is
      substantially increased in the remaining GABA neurons at 2-4 months after the
      initial seizure episode. Such increased labeling suggests that the remaining GABA
      neurons are part of a functional circuit and may be responding to the need for
      increased activity. Alterations also occur in at least one subunit of the GABA-A
      receptor. Labeling for the alpha(5) subunit mRNA is substantially decreased in
      CA1 and CA2 of pilocarpine-treated rats during the chronic, seizure-prone period.
      These findings emphasize the complexity of changes in the GABA system and
      indicate a need for evaluating the functional consequences of each of the
      changes. The initial loss of specific groups of GABA neurons could be a critical
      first step in the gradual development of epileptiform activity. While many of the
      subsequent changes in the GABA system may be considered to be compensatory,
      significant deficits of GABAergic function could remain.

PMID- 8985702
TI  - Neuron loss, mossy fiber sprouting, and interictal spikes after intrahippocampal
      kainate in developing rats.
AB  - This study determined neuron losses, mossy fiber sprouting, and interictal spike
      frequencies in adult rats following intrahippocampal kainic acid (KA) injections
      during postnatal (PN) development. KA (0.4 micrograms/0.2 microliters; n = 64)
      was injected into one hippocampus and saline into the contralateral side between
      PN 7 to 30 days. Animals were sacrificed 28 to 256 days later, along with age
      matched naive animals (controls; n = 20). Hippocampi were studied for: (1) Fascia
      dentata granule cell, hilar, and CA3c neuron counts; (2) neo-Timm's stained
      supragranular mossy fiber sprouting; and (3) hippocampal and intracerebral
      interictal spike densities (n = 13). Mossy fiber sprouting was quantified as the
      gray value differences between the inner and outer molecular layer. Statistically
      significant results (p < 0.05) showed the following: (1) Compared to controls,
      CA3c and hilar neuron counts were reduced in KA-hippocampi with injections at PN
      7-10 and PN 12-14 respectively and counts decreased with older PN injections.
      Granule cell densities on the KA-side and saline injected hippocampi were not
      reduced compared to controls. (2) In adult rats, supragranular mossy fiber
      sprouting was observed in 2 of 7 PN 7 injected animals. Compared to controls,
      increased gray value differences, indicating mossy fiber sprouting, were found on
      the KA-side beginning with injuries at PN 12-14 and increasing with older PN
      injections. On the saline-side only PN 30 animals showed minimal sprouting. (3)
      Mossy fiber sprouting progressively increased on the KA-side with longer
      survivals in rats injured after PN 15. Sprouting correlated positively with later
      PN injections and longer post-injection survival intervals, and not with reduced
      hilar or CA3c neuron counts. (4) On the KA-side, mossy fiber gray value
      differences correlated positively with in vivo intrahippocampal interictal spike
      densities. These results indicate that during postnatal rat development
      intrahippocampal kainate excitotoxicity can occur as early as PN 7 and increases
      with older ages at injection. This rat model reproduces many of the pathologic,
      behavioral, and electrophysiologic features of human mesial temporal lobe
      epilepsy, and supports the hypothesis that hippocampal sclerosis can be the
      consequence of focal injury during early postnatal development that progressively
      evolves into a pathologic and epileptic focus.

PMID- 8985703
TI  - Perirhinal cortex involvement in limbic kindled seizures.
AB  - Investigations into the anatomical substrate of temporal lobe epilepsy have
      yielded a number of important observations regarding the involvement of the
      piriform and perirhinal cortical areas in temporal lobe seizure propagation.
      Although early reports indirectly suggested that the circuits of the piriform
      cortex might act as a critical conduit for limbic seizure discharges to access
      motor systems, recent reports more strongly implicate the perirhinal cortex in
      this process. In the following report, we provide a brief summary of the earlier
      work involving the piriform cortex and its potential involvement in kindled
      limbic seizures. This is followed then by the results of several recent in vivo
      and in vitro electrophysiological studies that ascribe a critical importance for
      the perirhinal cortex in convulsive limbic seizures. Finally, since our
      anatomical studies indicated that the perirhinal cortex densely innervates the
      frontal motor cortex, we examined the involvement of this latter region in
      amygdala kindled seizures using the reversible functional lesion of cortical
      spreading depression. Based on these findings we suggest that the circuits of the
      perirhinal cortex may be important in the amplification and distribution of
      temporal lobe seizure discharges, providing access to structures that are capable
      of driving a convulsive response.

PMID- 8985705
TI  - Chronic epilepsy with damage restricted to the hippocampus: possible mechanisms.
AB  - We studied the time course and possible mechanisms of the development of chronic
      epilepsy following unilateral stimulation of the perforant path. After 24 h of
      perforant path stimulation by a modified Sloviter method, lesions were restricted
      to the hippocampus, except for 2 of 24 rats with minimal entorhinal neuronal
      injury in layer 3. Lesions were exclusively ipsilateral in the polymorph layer of
      the hilus and in CA4-CA3C, predominantly ipsilateral in CA3, in CA1 and in the
      granule cell layer. Feedforward and feedback inhibition were studied by paired
      pulse stimulation. In the week following inhibition, there was complete loss of
      GABAA-mediated, short interstimulus interval (ISI)-dependent inhibition and
      frequency-dependent inhibition, and also of GABAB-mediated long ISI-dependent
      inhibition. Yet no spontaneous seizures were observed at that time. In the next
      four weeks, we saw no evidence of increasing excitatory drive such as would be
      expected from recurrent mossy fiber sprouting. On the contrary, there was
      progressive return of inhibition. By four weeks post-lesion, the majority of
      animals had developed spontaneous recurrent seizures, and/or seizures on 2 Hz
      stimulation (never seen in controls), in spite of complete or near-complete
      recovery of short ISI-dependent, GABAA-mediated inhibition. A small but
      significant loss of frequency-dependent inhibition persisted, but individual
      animals with complete recovery of frequency-dependent inhibition showed
      spontaneous seizures, suggesting that loss of GABAA-mediated inhibition was not
      the direct cause of chronic epilepsy. GABAB-mediated, long ISI-dependent
      inhibition continued to show a significant loss. The ratio of the population
      spike amplitude at 250 microA to the maximal population spike amplitude, a
      measure of granule cell excitability, was unchanged immediately after
      stimulation, but increased in the next few weeks in a manner identical to that
      seen in kindling, suggesting the possibility that during the transient loss of
      inhibition, spontaneous kindling had occurred. Intracellular recordings from
      granule cells in hippocampal slices prepared from these animals showed a
      significant loss of GABAB-mediated slow inhibitory postsynaptic potentials
      (IPSPs). These data show that the sequellae of unilateral status epilepticus with
      damage restricted to the hippocampus are sufficient to cause chronic recurrent
      seizures. There is a possibility that chronic epilepsy is not the direct result
      of the loss of inhibitory drive or of a sprouting-induced increase in excitatory
      drive, but represents plastic changes akin to spontaneous kindling, possibly
      facilitated by loss of GABAB-mediated inhibition.

PMID- 8985704
TI  - Comparison of seizure related amino acid release in human epileptic hippocampus
      versus a chronic, kainate rat model of hippocampal epilepsy.
AB  - Recent microdialysis studies of excitatory and inhibitory amino acid release
      associated with paroxysmal hippocampal activity have found significant increases
      in the hippocampus of epileptic patients, but minimal or variable increases in
      animal models. One possible reason for the difference is that the animal models
      employed in these studies have not adequately reflected the pathophysiology of
      human epilepsy. The present study sought to verify the amino acid release
      reported in human epileptic hippocampus and then employs animal studies using a
      chronic rat model of epilepsy, in which rats exhibit spontaneous seizure activity
      3 to 4 months after injection of kainic acid into the hippocampus. In agreement
      with earlier reports, we found increases in glutamate, aspartate and GABA during
      seizures in human hippocampus. In addition we found increases in taurine which
      have not previously been reported. The chronic rat model shows increases in the
      same amino acids as in the human epileptic hippocampus, both during spontaneous
      seizures and stimulation evoked after-discharges (ADs). In contrast, minimal
      increases are elicited by hippocampal stimulation in control (non-kainate
      injected) animals. These results correlate with the degree of mossy fiber
      reorganization found in the dentate gyrus of kainate rats or epileptic humans.

PMID- 8985706
TI  - Functional changes in somatostatin and neuropeptide Y containing neurons in the
      rat hippocampus in chronic models of limbic seizures.
AB  - Using immunocytochemistry and in situ hybridization analysis of mRNA, we
      investigated the changes in the expression of somatostatin and neuropeptide Y
      (NPY) in the rat hippocampal principal neurons in kindling or after electrically
      induced status epilepticus (SE), two models of limbic epilepsy associated with
      different chronic sequelae of seizures and seizure-related neuropathology. At the
      preconvulsive stage 2 of kindling and after three consecutive tonic-clonic
      seizures (stage 5) but not after a single-discharge (AD), somatostatin and NPY
      immunoreactivity (IR) were markedly increased in interneurons of the deep hilus
      and the polymorphic cell layer and their presumed projections to the outer
      molecular layer of the dentate gyrus. Increased mRNA levels were observed in the
      same neurons. NPY IR and mRNA were highly expressed in pyramidal-shaped basket
      cells at both stages of kindling. IR was similar two days after stages 2 or 5 of
      kindling while less pronounced effects were observed one week after kindling
      completion. Peptide-containing neurons in the hilus appeared well preserved in
      spite of an average of 24% reduction of Nissl stained cells (p < 0.01) in the
      stimulated and contralateral hippocampus at stage 5. No sprouting of mossy fibres
      in the inner molecular layer was found as assessed by Timm staining. Thirty days
      after SE, somatostatin IR was slightly reduced or similar to controls in the
      ventral dentate gyrus and molecular layer in four or six rats (SE-I group) while
      in the two other post-SE rats (SE-II), somatostatin IR was lost. These changes
      were associated with a different extent of neurodegeneration as assessed by cell
      counting of Nissl stained sections. In the granule cells/mossy fibres NPY-IR was
      transiently expressed at stage 2 and after a single AD. Differently, NPY-IR was
      persistently enhanced in the mossy fibres of all post-SE rats particularly in the
      SE-II group. In these rats, NPY immunoreactive fibres were detected in the
      infrapyramidal region of the stratum oriens CA3 and in the inner molecular layer
      of the dentate gyrus very likely labeling sprouted mossy fibres. In the
      hippocampus proper of kindled rats, somatostatin and NPY IR were respectively
      enhanced in the stratum lacunosum moleculare, the subiculum and in the alveus
      while no significant changes were observed after SE. Changes in peptide
      expression were bilateral and involved both the dorsal and the ventral
      hippocampus. The lasting modifications in peptides IR and mRNA expression in
      distinct neuronal populations of the hippocampus may reflect functional
      modifications neurons and play a role in limbic epileptogenesis.

PMID- 8985707
TI  - Rapid and transient increases in cellular immediate early gene and neuropeptide
      mRNAs in cortical and limbic areas after amygdaloid kindling seizures in the rat.
AB  - Changes in transcription factor and neuropeptide gene expression are likely to be
      involved in the cascade of genetic and molecular events leading to permanent
      changes in neuronal activity associated with kindling and epilepsy. Both acute
      transient and delayed-sustained changes in transcription factor or immediate
      early gene (IEG) activity have previously been reported in response to different
      stimuli. In the present study in situ hybridization was used to investigate the
      possible time course (30 min-8 week) of IEG and neuropeptide mRNA induction in
      forebrain in a kindling model of epilepsy. Kindling was produced by daily
      unilateral stimulation of the amygdala. IEG mRNAs were detected using [35S]
      labelled oligonucleotide probes specific for c-fos, c-jun, NGFI-A (PC1) and PC3
      transcripts. Possible changes in the level of mRNAs encoding the neuropeptides
      somatostatin (SOM) and neuropeptide Y (NPY) were also studied. Stimulation
      induced seizures produced dramatic bilateral increases in all IEG mRNAs in the
      dentate gyrus after 30 min to 1 h. Ipsilateral or bilateral increases in c-fos
      and PC3 mRNA were observed in the piriform cortex of individual animals at 30 min
      post-stimulation. While the distribution and apparent basal expression of the
      different IEGs varied (NGFI-A and c-jun > c-fos and PC3), the degree of induction
      in the dentate gyrus was similar for all IEGs studied (i.e. 200-300%). No long
      term changes in IEG mRNA expression were detected beyond 2 h and up to 8 week
      after the last seizure. Increased levels of preproSOM and preproNPY mRNAs were
      consistently observed in hilar interneurons, but not in pyramidal or granule
      cells of the hippocampus, after 1-2 h. These increases were not maintained at
      later times. The short-term effects on IEG and neuropeptide mRNAs observed
      suggest that these changes are consequence of seizure activity with the
      development of kindling. In contrast, no evidence was found of any substantial,
      long-lasting effects on these parameters associated with the established kindled
      state.

PMID- 8985708
TI  - Kindling with clozapine: behavioral and molecular consequences.
AB  - Clozapine is an 'atypical' neuroleptic that improves symptoms of many patients
      with schizophrenia whose illness is resistant to treatment with other
      neuroleptics. Unlike the 'typical neuroleptics (chlorpromazine, haloperidol),
      clozapine does not induce extrapyramidal symptoms such as Parkinsonism and
      tardive dyskinesia in humans or catalepsy in the rat. However, clozapine
      frequently causes epileptiform EEG changes and causes seizures in 3-5% of
      patients treated with this drug in therapeutic doses. Clozapine also induces dose
      dependent myoclonus in the partially restrained rat. In the experiments reported
      here, partially restrained rats were administered repeated alternate day or
      weekly low, fixed doses of clozapine (1 mg/kg). This dose initially caused no
      behavioral change. Following the third and subsequent administrations, the same
      dose elicited an increasing number of myoclonic seizure-like jerks reaching 140/h
      following the 15th injection in rats receiving the same low dose of clozapine on
      alternate days and 160/h following the 9th injection in animals that received the
      same dose once weekly. These effects are consistent with kindling, i.e. a
      progressive increase of brain excitability following repeated administration of a
      fixed subconvulsive dose of an excitatory agent. Clozapine kindled animals
      exhibited a significantly different pattern of early gene expression in ventral
      tegmental area, origin of the mesolimbic-mesocortical dopamine system and in the
      anterior thalamic nuclei, compared with saline treated controls subjected to
      exactly the same recording conditions. The evidence of central nervous system
      excitation with clozapine may be important to the unique therapeutic effect of
      this atypical antipsychotic in the treatment of symptoms, especially the deficit
      symptoms, of schizophrenia.

PMID- 8985709
TI  - Cholecystokinin in anxiety.
AB  - Cholecystokinin (CCK) plays an important role in both the alimentary tract and
      the central nervous system (CNS). At present it seems to be the most abundant
      neuropeptide in the CNS. This paper reviews the CCK neuronal system and its
      interactions with gamma-aminobutyric acid (GABA) and serotonin (5
      hydroxytryptamine; 5-HT). In addition, its putative role in anxiety will be
      discussed on the basis of animal data and studies in healthy volunteers and panic
      disorder patients. According to these investigations, the CCK4 challenge test
      fulfills most criteria for an ideal panicogenic agent and evidence has been found
      that CCKB receptor antagonists might possess anxiolytic properties in man.

PMID- 8985710
TI  - The antinociceptive effect of fluvoxamine.
AB  - The authors conducted a study in order to evaluate the antinociceptive effects of
      the serotonin-selective reuptake inhibitor (SSRI) antidepressant fluvoxamine and
      its interaction with various opioid receptor subtypes. Male ICR mice were tested
      with a hotplate analgesia meter. Fluvoxamine elicited antinociceptive effect in a
      dose-dependent manner following i.p., i.t. and i.c.v. injection. Naloxone 10
      mg/kg s.c. did not abolish the fluvoxamine antinociceptive effect. At the next
      stage fluvoxamine was administered together with various agonists of opioid
      receptors. When administered together with opiates, fluvoxamine significantly
      potentiated analgesia at the kappa(3)-opioid receptor subtype (P < .005) and to a
      lesser extent, at the mu-, delta-, and kappa(1)-opioid receptors. We conclude
      that fluvoxamine alone induces an antinociceptive effect. This effect is mediated
      by non-opioid mechanism of action. These results suggest a potential role for
      fluvoxamine in the management of pain when co-administered with opioids at low
      doses.

PMID- 8985711
TI  - Piracetam and fipexide prevent PTZ-kindling-provoked amnesia in rats.
AB  - Deficit in active and inhibitory avoidance behaviour has been pentylenetetrazole
      (PTZ)-kindled rats. This supports the view that memory deficit is an integral
      part of epilepsy. In the present study we examined the effect of the nootropic
      drugs piracetam and fipexide on memory deficit induced by PTZ-kindling in shuttle
      box- and step-down-trained rats. The retention in piracetam- and fipexide-treated
      animals was significantly improved compared to the kindled controls. The
      mechanisms of action of the two drugs are considered. The favourable of nootropic
      drugs in cases of amnesia provoked by PTZ-kindling might be of interest in
      clinical practice.

PMID- 8985713
TI  - Bupropion induces sniffing: a possible dopaminergic mechanism.
AB  - The effect of bupropion, an antidepressant drug, on sniffing behaviour was
      examined in rats. Animals treated intraperitoneally (i.p.) with different doses
      of bupropion (5-40 mg/kg) showed sniffing behaviour in a dose-related manner.
      Pretreatment of animals (i.p.) with the dopamine antagonists SCH 23390 (0.025-0.1
      mg/kg) or sulpiride (12.5-50 mg/kg) decreased the sniffing induced by bupropion.
      Reserpine pretreatment (2.5 mg/kg, i.p., 18 h) alone and in combination with
      alpha-methyl-p-tyrosine (AMPT; 250 mg/kg, i.p.) also reduced the behaviour
      produced by the drug. The alpha-adrenoceptor phenoxybenzamine (5 and 10 mg/kg,
      i.p.) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg, i.p.)
      administered 60 min prior to bupropion did not affect the drug's effect on
      sniffing. Propranolol alone, however, induced sniffing. The antimuscarinic
      atropine (5 and 10 mg/kg, i.p.) administered 30 min prior to bupropion increased
      the bupropion response. Atropine alone induced vigorous sniffing. It is concluded
      that bupropion induced sniffing through a dopaminergic mechanism.

PMID- 8985712
TI  - Behavioral effects of CCKB receptor ligands in a validated simulation of panic
      anxiety in rats.
AB  - Animals or human subjects receiving brain stimulation in the dorsal
      periaqueductal gray matter (dPAG) show sudden fear-suggestive behavioral
      reactions and physical signs of autonomic activation which are reminiscent of the
      symptom profile characterizing a panic attack. An experimental situation in rats
      measuring dPAG stimulation self-interruption thresholds has been validated as
      realistically simulating several aspects of panic anxiety with objective signs of
      symptomatic and predictive validity using established antipanic and panicogenic
      agents; it was utilized here to evaluate the effects of various cholecystokinin B
      receptor ligands. A dose-dependent increase in self-interruption thresholds
      (antipanic-like effect) was recorded following injection of L-365,260 (3.2, 10
      and 32 mg/kg i.p.), a CCKB receptor antagonist with good brain penetration,
      whereas no significant changes in thresholds were recorded following CI-988 (3.2,
      10 and 32 mg/kg i.p.), a dipeptoid CCKB receptor antagonist with poor brain
      penetration. Latencies for self-interruption were not modified, suggesting that
      motor functions remained intact. No significant changes in self-interruption
      thresholds were recorded following peripheral administration of the CCKB receptor
      agonists CCK4 (0.03 to 0.32 mg/kg i.v.; 0.01 to 3.2 mg/kg i.p.) or the
      metabolically stabilized analog Boc-CCK4 (0.1 to 10 mg/kg i.p.). Systemic
      administration of the panicogenic compounds caffeine and yohimbine enhance acute
      anxiety in this model. These data indicate that, in the dPAG simulation of panic
      anxiety, central CCKB receptor blockade by L-365,260 induces antiaversive effects
      analogous to those observed following benzodiazepine receptor activation by
      clonazepam or alprazolam. Potency and efficacy of L-365,260 were lower than those
      of clonazepam or alprazolam, suggesting modest, but nonetheless authentic,
      antiaversive properties for this CCKB receptor antagonist. Lack of effects
      observed following peripheral administration of the agonists CCK4, and Boc-CCK4
      or of the dipeptoid antagonist CI-988 is likely to reflect restricted brain
      penetration of those compounds in rats; it furthermore excludes a contribution of
      peripheral gastrin and CCKA receptors to the antipanic-like properties of
      selective CCKB receptor antagonists such as L-365,260.

PMID- 8985714
TI  - Enhancement of antipsychotic-like properties of the dopamine D2 receptor
      antagonist, raclopride, by the additional treatment with the 5-HT2 receptor
      blocking agent, ritanserin, in the rat.
AB  - The effects of 5-HT2 receptor blockade on the ability of a dopamine (DA) D2
      receptor antagonist to produce suppression of conditioned avoidance response
      (CAR) and to produce catalepsy in rats were examined. It was found that
      ritanserin (2 mg kg-1 s.c.) enhanced the raclopride (0.1 mg kg-1 s.c.)-induced
      suppression of CAR without affecting raclopride-induced catalepsy at either
      maximal (4 mg kg-1 s.c.) or submaximal (0.2 mg kg-1 s.c.) doses. Considering the
      CAR performance as an index of mesocorticolimbic dopaminergic functions, it is
      concluded that 5-HT2 receptor blockade confers a limbic profile on the DA D2
      receptor antagonist.

PMID- 8985715
TI  - Interactions between ifenprodil and dizocilpine on mouse behaviour in models of
      anxiety and working memory.
AB  - The N-methyl-D-aspartate (NMDA) receptor polyamine site antagonist, ifenprodil,
      had no effect on spontaneous alteration or locomotor activity in the Y-maze when
      given alone. The NMDA receptor/ion channel blocker, dizocilpine, induced a
      deficit in spontaneous alteration, but when ifenprodil was co-administered with
      dizocilpine, it showed a strong tendency to attenuate the dizocilpine-induced
      deficit. In the plus-maze, ifenprodil had an anxiolytic profile which was
      accompanied by an increase in locomotion. Dizocilpine had an anxiolytic profile
      in this model and increased locomotor activity. When co-administered with
      dizocilpine, ifenprodil reduced both the anxiolytic and locomotor effects of
      dizocilpine. When co-administered with ifenprodil, cyclopentyladenosine (CPA) and
      1,3-dipropyl-8-cyclopentylxanthine (CPX) reduced the anxiolytic effect of
      ifenprodil. CPA and CPX in combination did not reverse the anxiolytic effect of
      ifenpropil. It is concluded that NMDA antagonists with different sites of action
      can show distinct behavioural profiles, with dizocilpine but not ifenprodil
      inducing a deficit in working memory, while both are anxiolytic. Blockade of NMDA
      receptors by ifenprodil, however, can preclude any response to dizocilpine. The
      anxiolytic activity of ifenprodil may involve the release of purines acting at
      adenosine receptors.

PMID- 8985716
TI  - Ammonium acetate challenge in experimental chronic hepatic encephalopathy induces
      a transient increase of brain 5-HT release in vivo.
AB  - Ammonia has been shown to cause release of neurotransmitters such as serotonin (5
      hydroxytryptamine; 5-HT) from synaptosomal preparations in vitro. In the present
      study, frontal neocortical extracellular levels of 5-HT and its major metabolite,
      5-hydroxyindole-3-acetic acid (5-HIAA), were determined in vivo by the use of
      microdialysis in portacaval shunted (PCS) rats, an experimental model of chronic
      hepatic encephalopathy (HE), prior to and after an acute coma-inducing
      administration of ammonium acetate (NH4Ac; 5.2 mmol/kg, i.p.). PCS rats displayed
      elevated (P < 0.01) 5-HIAA but unaltered 5-HT extracellular levels compared with
      controls, supporting the contention of an increased neocortical 5-HT metabolism
      but unaltered neuronal 5-HT output in chronic HE. However, a transient elevation
      of extracellular 5-HT levels was observed when PCS-NH4Ac rats were in coma.
      Increased brain ammonia may thus augment neuronal 5-HT release in chronic HE,
      which in turn could be a causative for precipitation of more severe stages of HE.

PMID- 8985717
TI  - Flumazenil attenuates the pituitary response to CRH in healthy males.
AB  - Differential effects of flumazenil (an antagonist) and midazolam (an antagonist
      at the benzodiazepine receptor) were studied in 8 healthy males.
      Adrenocorticotropic hormone (ACTH) and cortisol responses to a corticotropin
      releasing hormone (CRH) challenge were measured. ACTH response was significantly
      lower after flumazenil administration than after saline or midazolam. No
      significant treatment effect was found for the CRH-induced cortisol secretion.
      Our results agree with previous reports that point to an agonistic effect of
      flumazenil on pituitary-adrenocortical system activity and, moreover, may further
      support the anxiolytic activity of flumazenil in stimulated stress.

PMID- 8985718
TI  - alpha-Adrenergic regulation of human renal function.
AB  - Pharmacological and molecular cloning techniques have identified six human
      subtypes of alpha-adrenoceptors which are designated alpha 1A, alpha 1D, alpha
      2A, and alpha 2C. At the protein level human kidney expresses predominantly alpha
      2A-adrenoceptors while other alpha 2-adrenoceptor subtypes or alpha 1
      adrenoceptors have not been detected consistently in radioligand binding studies.
      However, the presynaptic receptors, which inhibit noradrenaline release in the
      human kidney, appear to belong to the alpha 2C-subtype. Intrarenal infusion of
      the nonselective alpha-adrenoceptor antagonist, phentolamine, and of the
      selective alpha 2-adrenoceptor antagonist, yohimbine, but not of the selective
      alpha 1-adrenoceptor antagonist, doxazosin, increase renal blood flow and renin
      release in hypertensive patients undergoing diagnostic renal angiography. Thus,
      alpha 2- but not alpha 1-adrenoceptors appear to mediate a tonic renal
      vasoconstriction and inhibition of renin release. Effects of systemically given
      alpha 1-adrenoceptor agonists and antagonists are difficult to interpret on a
      mechanistic level since direct effects in the kidney and indirect effects due to
      baroreflex activation and peripheral presynaptic and central sympatholytic
      actions may at least partially offset each other. Moreover, some of these drugs
      may additionally act independent of alpha-adrenoceptors, for example, via
      imidazoline recognition sits. The net result in a given subject may depend on the
      endogenous sympatho-adrenal tone. Thus, for each target population of interest,
      effects have to be described empirically for each drug.

PMID- 8985719
TI  - Metabolism and toxicity of coumarin on cultured human, rat, mouse and rabbit
      hepatocytes.
AB  - We compared the cytotoxic effect of coumarin and its derivatives, 7
      hydroxycoumarin (7-OHC), 4-hydroxycoumarin (4-OHC), o-hydroxyphenyl acetic acid
      (OHPAA) and o-coumaric acid (CA), on cultured hepatocytes from human, rat, mouse
      and rabbit liver. At 10(-5) and 5 x 10(-5) M, coumarin and its derivatives did
      not give rise to any signs of toxicity on cultured hepatocytes of the four
      species. At 10(-4) M, coumarin, but not its derivatives, induced release of
      lactate dehydrogenase (LDH) into the medium, especially in rat hepatocyte
      cultures. Intracellular LDH activities were correspondingly reduced. The
      cytotoxic effect of coumarin in cultured rat hepatocytes was evidenced on
      morphological examination and from the results of the 3-(4,5-dimethylthiazol-2
      yl)-2,5- diphenyltetrazolium (MTT) reduction test. At higher concentrations (5 x
      10(-4) M), 7-OHC and CA were also found to be cytotoxic in cultured rat
      hepatocytes. The cytotoxic effect of coumarin (5 x 10(-4) M) was decreased in the
      presence of SKF 525-A, a cytochrome P450 inhibitor. Interspecies comparisons
      showed that rat hepatocytes were the most sensitive to the toxicity of coumarin
      and its derivatives, whereas human hepatocytes were the most resistant. Our
      results suggest that the cytotoxicity of coumarin is metabolism and species
      dependent. Thus, the rat may not be a suitable model for evaluating the
      pharmacological hazards of coumarin in humans.

PMID- 8985720
TI  - Effects of graded hemorrhage on short-term variability of blood pressure in
      conscious rats.
AB  - A controlled graded bleeding was performed in conscious rats with 15 min
      intervals between two withdrawals, in order to induce a 25% blood loss without
      hypotension. Heart rate (HR) was unaffected as well. The spectral profiles of
      systolic blood pressure (SBP) analyzed on 51.2 s segments exhibited increases in
      the high frequency (HR, respiratory) component. This increase paralleled the
      blood loss with a rise ranging from 20% for a 1 mL/kg hemorrhage to 90% for a 11
      mL/kg removal. These changes were associated with increases in the mid-frequency
      (MF, Mayer waves) component of SBP variability. These latter rises were between
      30 and 40% of the control value. Breathing frequency (BF) and blood gases were
      unaltered following hemorrhage. A shift of fluid occurred during the 3 h session
      as reflected by the significant hemodilution. Rats were also bled after
      pretreatment with prazosin (1 mg/kg) or with an association of prazosin (1 mg/kg)
      and losartan (10 mg/kg). These treatments increased HR. A marked fall in SBP
      occurred with the double blockade. Hemorrhage determined a relative bradycardia
      together with the SBP decrease (reversible shock) after prazosin and losartan
      treatment. Prazosin determined opposite changes in MF (-33%) and HF (+58%) SBP
      components. A further decrease in the MF SBP component was observed following the
      double blockade. Spectral profiles following hemorrhage were unchanged compared
      to the prehemorrhage blocked levels. Therefore graded nonhypotensive, ie,
      normotensive hemorrhage in rats, was associated with progressive increases in the
      respiratory SBP variations, estimated from the SBP spectrum. This sensitive index
      could reflect the low preload state due to hypovolemia. The hemorrhage-induced MF
      SBP component increase could reflect an increased sympathetic vasomotor drive,
      prevented with prazosin, as a reflex adjustment to hypovolemia. Renin activation
      could also contribute to the genesis of MF waves and its role in maintaining BP
      following hemorrhage was exemplified with alpha 1-adrenoceptor blockade.

PMID- 8985721
TI  - Aerosolized tachykinin antagonists inhibit pentamidine-induce bronchoconstriction
      in guinea pigs.
AB  - To investigate the role of tachykinins in pentamidine-induced bronchoconstriction
      and airway microvascular leakage in the guinea pig, we examined the effects on
      bronchoconstriction and microvascular leakage of the nonpeptide antagonists of
      NK1 and NK2 tachykinin-receptors, respectively, CP-96,345 and SR 48968.
      Respiratory system resistance was measured by the occlusion method in
      anaesthetized, tracheotomized and mechanically ventilated guinea pigs. Airway
      microvascular permeability was evaluated by measuring the quantity of Evans blue
      dye in the trachea and main bronchi. Aerosolized CP-96,345 or SR 48968 partially
      abolished pentamidine-induced bronchoconstriction (at 5 to 30 mg/mL pentamidine;
      60 breaths) whereas the combination of the two prevented it. In contrast, CP
      96,345 and SR 48968 did not prevent the increase in airway microvascular
      permeability induced by pentamidine (50 mg/mL; 90 breaths) whether they were
      administered separately or together, by aerosol or intravenously. These results
      demonstrate that in the guinea pig, pentamidine-induced bronchoconstriction is
      mediated through both NK1 and NK2 tachykinin-receptor activation and that when
      directly administered into the airways, tachykinin antagonists effectively
      prevent pentamidine-induced bronchoconstriction.

PMID- 8985722
TI  - The effect of the potassium channel activator, cromakalim, on antidepressant
      drugs in the forced swimming test in mice.
AB  - The forced swimming test (FST) is a widely used behavioural model to predict
      potential antidepressant (AD) action of compounds in humans. It has been
      previously shown that pretreatment with lithium, quinine and clonidine had
      additive effects on AD drugs in the FST, an effect proposed to be a result of
      potassium channel blockade. It is possible that pretreatment with potassium
      channel openers may induce opposite effects to those seen following pretreatment
      with potassium channel blockers in the FST. Pretreatment with cromakalim (CROM)
      (1 mg/kg, intraperitoneally [i.p.]) antagonized the anti-immobility effect of the
      mixed noradrenaline (NA)/5-hydroxytryptamine (5-HT) reuptake inhibitors
      imipramine and amitriptyline (P < 0.05). CROM administration (0.06 and 1 mg/kg,
      i.p.) also blocked the AD-like effects of the specific NA reuptake inhibitor,
      desipramine, and the selective serotonin reuptake inhibitor, paroxetine (P < 0.05
      and P < 0.01, respectively). Pretreatment with CROM via gavage (1 mg/kg)
      antagonized the AD-like effects of imipramine, amitiptyline, desipramine and
      paroxetine. CROM treatment (via i.p. route or gavage) did not have any
      significant effect on the anti-immobility activity of the atypical AD mianserin
      at any of the doses employed. Another potassium channel opener, minoxidil
      (MINOX), which does not cross the blood-brain barrier, was also tested to
      eliminate the possibility that CROM may be acting via peripheral/local
      mechanisms. MINOX (32 mg/kg) failed to antagonize anti-immobility effects of any
      of the AD tested. In conclusion, the results of the present study suggest that
      CROM is only acting on drugs involved with neurotransmitter uptake inhibition.

PMID- 8985723
TI  - Peripheral alpha 2-adrenoceptor-mediated sympathoinhibitory effects of mivazerol.
AB  - Mivazerol is a new compound that could potentially reduce perioperative
      cardiovascular morbidity and mortality in patients with or at risk of coronary
      disease and submitted to surgery. This action of mivazerol depends on a well
      documented centrally mediated reduction in sympathetic nerve activity, but a
      direct peripheral decrease in sympathetic neurotransmitter release induced by
      activation of prejunctional alpha 2-adrenoceptors located on sympathetic nerve
      endings could also contribute. To investigate this issue, the effects of
      mivazerol on the pressor, systemic and regional hemodynamic (pulsed Doppler
      technique) as well as on the cardiac responses to electrical stimulation of the
      spinal cord (SCS) were measured in pithed rats in the absence and in the presence
      of mivazerol. Mivazerol exerted strong sympathoinhibitory effects: SCS-induced
      increases in blood pressure, total peripheral resistance and heart rate were dose
      dependently reduced by mivazerol, but among the regional vascular beds
      investigated, only the hindlimb vasoconstrictor responses were significantly drug
      affected. All these sympathoinhibitory effects of mivazerol were abolished by
      prior yohimbine administration. Simultaneously, mivazerol did not induce any
      postjunctional adrenoceptor blockade as it did not affect noradrenaline cardiac
      and hemodynamic effects. On the contrary, through postjunctional alpha 2
      adrenoceptor stimulation, mivazerol, in this pithed preparation, dose-dependently
      increased blood pressure, total peripheral and hindlimb vascular resistances, but
      heart rate was not affected. We conclude that, in the pithed rat, mivazerol
      exerts strong peripheral sympathoinhibitory effects. The mechanism involved is
      prejunctional alpha 2-adrenoceptor activation as i) mivazerol does not display
      any postsynaptic alpha-adrenoceptor blocking effect--it even behaves as as
      postsynaptic alpha 2-adrenoceptor agonist--and ii) yohimbine abolishes
      mivazerol's sympathoinhibitory effects. Thus, direct peripheral together with
      central mechanisms contribute to mivazerol's sympathoinhibitory effects and
      ultimately to its cardioprotective action.

PMID- 8985724
TI  - Modulation by alcohol and methadone of 2-deoxyglucose-stimulated pancreatic
      secretion in the rat.
AB  - Alcohol intake is a major problem in drug addicts, and it is not clear whether
      the effects of alcohol and opiates are additive or potentiating. Vagally
      stimulated pancreatic secretion in rats is potently inhibited by opiates acting
      centrally at mu-receptors. In the present experiments, we determined the effects
      of methadone on 2-deoxyglucose (2DG)-stimulated pancreatic secretion in rats
      treated with acute (1.9 g/kg.3 h, intravenously) or chronic (1 or 3 month
      drinking) ethanol. In both acute and 1 month chronic alcoholic rats, methadone
      administered at its 50% inhibitory dose (ID50) reduced by about 50% 2DG
      stimulated pancreatic secretion of sodium, bicarbonate and protein, and ethanol
      had only faint, nonsignificant inhibitory effects. In 3 month chronic alcoholic
      rats, similar results were obtained, but methadone inhibited 2DG-stimulated
      pancreatic secretion by 60 to 90% in these older rats. No significant interaction
      was found in any condition between ethanol and methadone, suggesting that they
      had only additive, but not potentiating effects in this method.

PMID- 8985725
TI  - Beta adrenoceptor density in patients with left-sided valvular regurgitation.
AB  - Aortic regurgitation differs from mitral regurgitation in that it is a result of
      combined volume and pressure overload, while the latter represents an almost pure
      volume overload. In this study, we tested the possibility that these two forms of
      left ventricular volume overload exert different effects on beta-adrenoceptor
      density. Lymphocyte (n = 33) and myocardial (n = 22) beta-adrenoceptor densities
      were evaluated by [125I]-iodocyanopindolol binding in volume-overload patients
      with left heart valvular disease, compared with 31 healthy donor blood and 15
      donor heart controls, made available as a result of failing to get matching
      recipient. The total lymphocyte (LC) beta-adrenoceptor density decreased from
      43.4 +/- 5.5 fmol mg-1 protein in controls to 9.2 +/- 2.7 fmol (P < 0.001) in
      heart valvular patients. In the myocardial controls, the left ventricular (LV)
      receptor density was 126.7 +/- 19.5 fmol; right ventricular (RV), 123.1 +/- 14.6
      fmol; left atrial (LA), 81.6 +/- 10.5 fmol; and right atrial (RA), 108.1 +/- 14.5
      fmol mg-1 protein. Compared to this group, the total LV-receptor density of the
      patients decreased by 63%, RV by 54%, LA by 31% and RA by 34%. The decrease in
      receptor density exhibited a positive correlation with increasing ejection
      fractions in both the left (r = 0.38) and right (r = 0.44) ventricles, indicating
      that the former was dependent on the extent of the disease. These changes were
      accompanied by a 44% increase in plasma epinephrine, 13% in norepinephrine and a
      27% decrease in dopamine levels. Based on the predominant left ventricular volume
      overload classified as aortic regurgitation (AVR), mitral regurgitation (MVR),
      and mixed aortic and mitral regurgitation (MOL), the attenuation in myocardial
      receptor densities showed the following trend: MOL > AVR > AVR. The results show
      a global reduction in myocardial and LC beta-adrenoceptor density, which depends
      on the origin and the gravity of the LV volume overload.

PMID- 8985726
TI  - Formulas and tables for the determination of sample sizes and power in clinical
      trials for testing differences in proportions for the matched pair design: a
      review.
AB  - This paper is a compendium of exact and asymptotic formulas and tables for
      calculating the sample size in a clinical trial for a matched-pair design
      involving a dichotomous outcome. Formulas for calculating power given the sample
      size are also given.

PMID- 8985727
TI  - Ovarian function in fragile X carriers.

PMID- 8985728
TI  - Pulmonary hypertension of the newborn and urogenital anomalies in two male
      siblings: a new family with misalignment of pulmonary vessels.
AB  - The association of pelvi-ureteric junction obstruction (PUJO) and rapidly fatal
      persistent pulmonary hypertension of the newborn (PPHN) has been observed in two
      male siblings. PUJO was also observed in a maternal uncle, whose daughter
      suffered from vesico-ureteral reflux (VUR). In both patients, histopathologic
      study of the lungs showed misalignment of pulmonary veins (MAPV), which is a rare
      autosomal recessive condition leading to severe PPHN and death within the
      neonatal period. It has occasionally been described associated with PUJO. The
      authors point out that: i: MAPV has to be carefully searched in case of PPHN; ii:
      PUJO could be an important finding associated with MAPV, and the only prenatal
      indication of this lethal condition.

PMID- 8985729
TI  - Oculocerebrocutaneous syndrome: a case report, a follow-up, and differential
      diagnostic considerations.
AB  - Oculocerebrocutaneous syndrome consists essentially of orbital cysts and
      microphthalmia/anophthalmia, focal dermal defects, skin appendages and
      malformations of the central nervous system. Up to now, about 20 sporadic cases
      have been reported. Limited information is available on the clinical spectrum and
      on the natural history. We present the long-term follow-up of a 19 year-old
      patient who was one of the first two patients described by Delleman and Oorthuys
      in 1981. Furthermore, we report on a new case presenting with bilateral
      anophthalmia and orbital cysts, typical skin lesions, a complex brain
      malformation and cleft lip palate. This infant died due to the severe cerebral
      malformations at the age of 10 months. Encephalocraniocutaneous lipomatosis,
      focal dermal hypoplasia and microphthalmia with linear skin defects (MLS)
      syndrome are discussed as the most important differential diagnostic entities.

PMID- 8985730
TI  - Hyperkalemic periodic paralysis caused by recurring mutation in the adult muscle
      sodium channel alpha-subunit gene.
AB  - Linkage studies and mutation analysis were performed in two Swedish families with
      hyperkalemic periodic paralysis (HYPP), an autosomal dominant inherited disorder
      characterized by episodic muscle weakness associated with increasing or high
      levels of serum potassium. The gene for HYPP is the gene encoding the alpha
      subunit of the sodium channel of adult human skeletal muscle (SCN4A). SCN4A has
      been localized on chromosome 17 q closely linked to the human growth hormone
      gene. Linkage between a microsatellite polymorphism in the SCN4A gene and the
      disease was shown in two Swedish families (Z = 12.10 theta = 0). Sequence
      analysis revealed that the two Swedish families have got a C to T transition at
      position 2188 in the cDNA. At the protein level this Thr 704 to Met mutation is
      located in the fifth membrane spanning segment of domain II of the protein, as
      previously described (28). The mutation was linked to different microsatellite
      alleles regarding both a (GT)n and a (GA)n repeat in the gene. Either the
      families are related and new mutations have occurred in both microsatellites when
      the pedigrees were separated or the mutation has arisen independently in the two
      families analysed. From the mutant alleles characterized so far it seems as if a
      limited number of mutations is present in this gene.

PMID- 8985731
TI  - Microcephaly, macrotia, unusual mimics and mental retardation syndrome: new
      syndrome or variant of De Lange type 2 syndrome.
AB  - We report a boy who shows a severe microcephaly, with mild mental retardation and
      hypotonia, and a dysmorphic facies: (flat profile, arched eyebrows, mild ptosis,
      short nose with raised basis, large tip and anteverted nares, long, smooth
      philtrum, narrow mouth with down turned corners, very large, backward tilted
      ears, with a prominent lobule, retrognathism and very small and widely spaced,
      although normally shaped teeth. Vesicoureteral reflux was present. The mother
      showed similar aspect, large ears, and a grinning smile. This appear to represent
      an undescribed phenotype which share some resemblance to mild Cornelia de Lange
      and Kabuki syndromes.

PMID- 8985732
TI  - Floating-Harbor syndrome. A neuropsychological approach.
AB  - We describe a six year old Mexican girl whose clinical picture (short stature
      with delayed bone age, language difficulties and triangular face with prominent
      nose) was compatible with the diagnosis of Floating-Harbor Syndrome (FHS). A
      neuropsychological evaluation disclosed a mild mental retardation, a constructive
      apraxia, a comprehensive and expressive language impairment. The analysis of the
      present case and sixteen patients previously described establishes that the FHS
      is mainly characterized by proportionate short stature with significantly delayed
      bone age, delayed expressive language and peculiar face.

PMID- 8985733
TI  - Ways of announcing a late-onset, heritable, disabling disease and their
      psychological consequences.
AB  - The way of announcing a late-onset, heritable, disabling disease, and the impact
      of this realisation on the patient's life, were studied by means of unstructured
      interviews conducted with 10 neurologists and 22 patients. All physicians
      announced the name of the disease to the patient, and considered it important to
      do so. At the same time they also provided explanations concerning the
      unpredictable prognosis, the absence of curative therapy, and genetic
      transmission. It was extremely shocking for the patients to learn that their
      illness is a myopathy and furthermore that it is genetically transmissible. This
      shock was linked to the naming of the disease, which represented an abrupt
      transition in the patient's life. Patients feel that this moment marks the
      beginning of social exclusion. A strong disavowal of the disease is developed,
      regarding its disabling and heritable characteristics. This disavowal hampers
      reconstruction of the personality. A post-diagnostic follow-up by a genetic
      counsellor is highly recommended for patients and relatives alike. This should
      allow the patient to mourn his/her previous life, a prerequisite for positive
      rebuilding.

PMID- 8985734
TI  - Relationships of the 2642 deletion polymorphism (delta 2642) in the huntingtin
      gene with the CAG repeat expansion length and age at onset of the disease.
AB  - The deletion of 3bp at codon positions 2642-2645 (delta 2642) of the gene mutated
      in Huntington's disease (HD) was analysed on the normal (N) and HD chromosomes of
      79 French families affected with HD, and previously typed for the (CAG)n repeats.
      delta 2642 Polymorphism has been found over-represented on HD chromosomes, the
      relative risk of HD with the deletion being at a value of 8.26. In this study,
      the presence of the deleted allele on HD chromosomes increases the (CAG)n number
      (47.93 +/- 1.80 versus 43.50 +/- 2.78) and decreases the age of onset (41.34 +/-
      2.09 versus 36.90 +/- 2.41) in the patients with versus without delta 2642; so
      the deletion may add to the severity of the disease. Our studies of delta 2642 on
      N chromosomes confirm that the deletion event occurs on N chromosomes with a
      (CAG)n allele length at the upper end of the normal size range.

PMID- 8985735
TI  - Attitudes of German persons at risk for Huntington's disease toward predictive
      and prenatal testing.
AB  - Huntington's disease is an autosomal dominant neurodegenerative disorder
      characterized by involuntary movements, psychological deterioration and dementia.
      Indirect predictive testing by linkage analysis has been possible since 1983;
      direct predictive testing by detecting the instable CAG-repeat has been possible
      since 1993. Persons at risk were asked, by questionnaire, about their motivation
      and regarding attitude taking part in indirect and direct predictive and prenatal
      diagnostics. About half of the interrogated German persons at risk wish to
      undertake DNA analysis, whereas 32.7% do not want to take part in a direct
      predictive test. Motives for taking the test are the same as those mentioned in
      the literature (certainty of carrier status, decisions concerning marriage and
      further children, planning a career). Motives for not taking the test mostly
      involve psychological problems in coping with the test result. 45.7% wish to
      undergo a direct prenatal test (main cause: certainty of the gene status of the
      child), whereas 27% would not take this test (because of non-toleration of
      abortion). Only statistical trends could be seen between the intention to take
      the predictive or prenatal test and some social and demographic variables. The at
      risk persons would not change their attitudes regarding indirect or direct
      predictive and prenatal DNA analysis; they seem to have a confirmed opinion about
      molecular genetics, mostly depending on familial and social background.

PMID- 8985736
TI  - Variable expression of phenotype in offspring with partial monosomy 7q and
      partial trisomy 8p in a family with a rcp (7;8)(134;p12) translocation.
AB  - We report a female fetus with partial 7q monosomy and partial 8p trisomy, as the
      unbalanced product of a familial balanced reciprocal translocation; rcp
      t(7;8)(134:p12)mat. Among pregnancies from translocation carriers in this family,
      there has been a high incidence of first trimester miscarriages. Three unbalanced
      offsprings with a partial 7q monosomy and partial 8p trisomy were diagnosed after
      prenatal investigations. One female fetus with this unbalanced karyotype has
      previously been reported. She had a multiple congenital anomalies (MCA) syndrome.
      In contrast, the present female fetus with the same abnormal karyotype shows only
      mild facial dysmorfism.

PMID- 8985737
TI  - A case of VATER association associated with 9qh+.

PMID- 8985738
TI  - Holt-Oram syndrome with associated postaxial and central polydactyly. Further
      evidence for genetic heterogeneity in the Holt-Oram syndrome.

PMID- 8985739
TI  - Predictive and prenatal genetic testing in hereditary ataxia's. Report of a
      workshop.

PMID- 8985740
TI  - Na(+)-dependent glucose transporter SGLT1 is localized in the apical plasma
      membrane upon completion of tight junction formation in MDCK cells.
AB  - SGLT1, an isoform of Na(+)-dependent glucose transporters, is localized at the
      apical plasma membrane in the epithelial cells of the small intestine and the
      kidney. In the present study we examined its location in SGLT1 cDNA-transfected
      MDCK cells, which form an epithelial sheet connected by tight junctions in
      culture. Formation of tight junctions was monitored by staining for occludin, an
      integral tight junction protein. In the cells demarcated by an uninterrupted
      occludin meshwork, SGLT1 was specifically localized at the apical plasma
      membrane, showing that SGLT1 has a signal to accomplish this restricted
      localization. In the cells with little or no occludin accumulation in the tight
      junction, however, SGLT1 was present along the entire aspect of the plasma
      membrane. Similar distribution of SGLT1 was observed in the cells as long as the
      occludin meshwork remained incomplete. These observations suggest that apical
      localization of SGLT1 occurs upon the completion of the uninterrupted meshwork of
      tight junctions.

PMID- 8985741
TI  - FA1 immunoreactivity in endocrine tumours and during development of the human
      fetal pancreas; negative correlation with glucagon expression.
AB  - Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor
      (EGF)-like repeats. It is closely similar to the protein translated from the
      human delta-like (dlk) cDNA and probably constitutes a proteolytically processed
      form of dlk. dlk is homologous to the Drosophila homeotic proteins delta and
      notch and to the murine preadipocyte differentiation factor Pref-1. These
      proteins participate in determining cell fate choices during differentiation. We
      now report that FA1 immunoreactivity is present in a number of neuroectodermally
      derived tumours as well as in pancreatic endocrine tumours. A negative
      correlation between FA1 and glucagon immunoreactants in these tumours prompted a
      reexamination of FA1 immunoreactants during fetal pancreatic development. At the
      earliest stages of development, FA1 was expressed by most of the non-endocrine
      parenchymal cells and, with ensuing development, gradually disappeared from these
      cells and became restricted to insulin-producing beta cells. Throughout
      development FA1 was not detected in endocrine glucagon, somatostatin or
      pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed
      glucagon were negative for FA1. Thus, there was a negative correlation between
      FA1 and glucagon both in tumours and during development. These results, together
      with FA1/dlk's similarity with homeotic proteins, point to a role of FA1 in islet
      cell differentiation.

PMID- 8985742
TI  - CD44 isoform expression in the diffuse neuroendocrine system. I. Normal cells and
      hyperplasia.
AB  - Isoforms of the transmembrane glycoprotein CD44, which are generated by
      alternative splicing of nine variant exons, have been implicated in tumor cell
      adhesion, invasion and metastatic spread and may be indicators of the degree of
      tumor differentiation. Since little is known about the distribution of CD44 in
      non-neoplastic neuroendocrine cell types, we systematically investigated 42
      samples of tissue from different organs, including the pituitary gland, thyroid,
      parathyroid, adrenal gland, lung, pancreas, stomach, duodenum, jejunum, ileum,
      appendix, and colon, immunohistochemically for the expression of CD44 standard
      and variant exon-encoded gene products (CD44v3, v4, v5, v6, v9). Furthermore,
      double immunolabeling for CD44 and a variety of peptide hormones was applied to
      characterize the different neuroendocrine cell types. Our results show that
      neuroendocrine cells derived from the neuroectoderm lack CD44 immunoreactivity.
      However, those originated from the endoderm exhibit a variable CD44
      immunostaining which is related to their anatomical localization and the degree
      of differentiation irrespective of the hormone produced. Furthermore, we
      demonstrate that CD44 positive neuroendocrine cells predominantly express CD44
      isoforms of the epithelial type and that hyperplastic clusters of neuroendocrine
      cells of pancreatic ducts express CD44 most probably as a sign of
      dedifferentiation.

PMID- 8985744
TI  - Characterisation of substance P-induced endocytosis of NK1 receptors on enteric
      neurons.
AB  - Immunoreactivity for NK1 receptors is confined to specific nerve cell bodies in
      the guinea-pigileum, including inhibitory motor neurons and secretomotor neurons.
      In the present work, endocytosis of NK1 receptors in these enteric neurons was
      studied following addition of substance P (SP) to isolated ileum. NK1 receptors
      were localised with antibodies against the C-terminus of this receptor. Some
      preparations were incubated with SP tagged with the fluorescent label, Cy3.18, so
      that the fate of SP bound to receptors could be followed. Preparations were
      analysed by confocal microscopy. In tissue that was incubated at 4 degrees C in
      the absence of SP, most NK1 receptor immunoreactivity (IR) was confined to
      surface membranes of nerve cells. At 37 degrees C in the presence of 10(-7) M SP
      (plus 3 x 10(-7)M tetrodotoxin to prevent indirect activation via other neurons)
      the neuronal NK1 receptor was rapidly internalised. After 5 min, NK1 receptor IR
      was partially internalised, at 20 min NK1 receptor IR was throughout the
      cytoplasm and in perinuclear aggregates and at 30 min it was again at the cell
      surface. SP-induced NK1 receptor endocytosis was inhibited by the specific NK1
      receptor antagonist, SR140333. Cy3-SP was colocalised with NK1 receptor IR and
      was internalised with the NK1 receptor. These results show that enteric neurons
      exhibit authentic NK1 receptors that are rapidly internalised when exposed to
      their preferred ligand.

PMID- 8985743
TI  - CD44 isoform expression in the diffuse neuroendocrine system. II. Benign and
      malignant tumors.
AB  - The membrane glycoprotein CD44 may be associated with aggressive behavior,
      dissemination, and poor prognosis of a variety of human tumors. In order to
      extend our knowledge on the expression and significance of CD44 in cells of the
      dispersed neuroendocrine system we investigated a spectrum of 134 neuroendocrine
      tumors, including pituitary adenomas, medullary thyroid carcinomas, parathyroid
      adenomas, pheochromocytomas, neuroblastomas, small-cell lung carcinomas, and
      bronchopulmonary, pancreatic, and gastrointestinal neuroendocrine tumors
      immunohistochemically for CD44 standard and variant exon-encoded gene products
      (CD44v3, -v4, -v5, -v6, -v9). Furthermore, we compared protein expression with
      that of CD44 mRNA by reverse-transcriptase PCR and Southern blot hybridization in
      a subset of tumors. Our results show that CD44 expression is correlated with the
      "histogenetic origin" of the appropriate neuroendocrine neoplasm. Endoderm
      derived tumors generally express 3'-end CD44 variant exon-containing isoforms,
      whereas neural crest-derived tumors rarely are positive for CD44. Furthermore, we
      provide evidence that CD44 expression is not correlated with metastatic disease
      or a particular hormonal phenotype but exhibits an association with the degree of
      cellular differentiation. Thus, CD44 is not useful as marker for malignancy or
      prognosis. The number of patients with clinical follow-up data in our study was
      too small to allow definite conclusions about a possible correlation between CD44
      expression and prognosis. But CD44 may help to better classify neoplasms with an
      unclear neuroendocrine phenotype.

PMID- 8985746
TI  - Dense granular bodies: a novel nucleoplasmic structure in hibernating dormice.
AB  - Dense granular bodies (DGB) are particular structural constituents observed in
      cell nuclei of different tissues-liver, pancreas, brown adipose tissue, adrenal
      cortex-of hibernating dormice. They appear as strongly electron-dense clusters of
      closely packed granules, with thin fibrils spreading out at their periphery. DGB
      always occur in the nucleoplasm, sometimes making contact with other nuclear
      structural constituents typical of the hibernating state, such as coiled bodies,
      amorphous bodies and nucleoplasmic fibrils. DGB are present only during deep
      hibernation and rapidly disappear upon arousal from hibernation. Cytochemical and
      immunocytochemical analyses showed that DGB contain ribonucleoproteins and
      several nucleoplasmic RNA processing factors, suggesting that DGB can represent
      accumulation sites of splicing factors which are provided to splicing sites when
      normal metabolic activity is rapidly restored during arousal.

PMID- 8985745
TI  - Disturbed structural interactions between microfilaments and tight junctions in
      rat hepatocytes during extrahepatic cholestasis induced by common bile duct
      ligation.
AB  - Microfilaments in epithelial cells are important for the structural and
      functional integrity of tight junctions. In the present study, we examined the
      relationship between microfilaments and tight junctions in hepatocytes of rat
      liver following common bile duct ligation (CBDL) for up to 2 weeks. Actin
      filaments and tight junctions were studied by fluorescence microscopy using 7
      nitrobenzene-2-oxa-1,3-diazole phallacidin (NBD-ph) and an anti-ZO-1 antibody,
      respectively. Double-stained sections were examined with confocal laser scanning
      microscopy (CLSM). Electron microscopy was applied for the assessment of
      structural alterations in microfilaments and in tight junctions with detergent
      extraction and freeze-fracture preparations. Our results showed that F-actin was
      present at the entire plasma membrane of hepatocytes in control liver, whereas
      CBDL increased the amount of F-actin mainly at the bile canalicular and lateral
      plasma membranes. Simultaneously, the immunofluorescence of ZO-1 underwent
      striking changes, i.e., from a uniform to an irregular staining pattern with
      various fluorescence intensities. CLSM demonstrated a colocalization of ZO-1 and
      F-actin in control liver and its deterioration in CBDL liver. Electron microscopy
      showed marked alterations of microfilaments and tight junctions due to CBDL. It
      is concluded that actin filaments are intimately associated with tight junctions
      in normal hepatocytes. CBDL impairs this association by progressively diminishing
      the structural interaction between F-actin and ZO-1, which may in turn lead to
      functional disturbances of tight junctions.

PMID- 8985747
TI  - Fluorescence and confocal laser scanning microscopy imaging of elastic fibers in
      hematoxylin-eosin stained sections.
AB  - We have studied the possibility of associating fluorescence microscopy and
      hematoxylin-eosin staining for the identification of elastic fibers in elastin
      rich tissues. Elastic fibers and elastic laminae were consistently identified by
      the proposed procedure, which revealed itself to be easy and useful for the
      determination of such structures and their distribution. The fluorescence
      properties of stained elastic fibers are due to eosin staining as revealed by
      fluorescence analysis of the dye in solution, with no or only minor contribution
      by the elastin auto-fluorescence. The main advantage of this technique resides in
      the possibility of studying the distribution of elastic fibers in file material
      without further sectioning and staining. The use of the confocal laser scanning
      microscope greatly improved the resolution and selectivity of imaging elastic
      fibers in different tissues. The determination of the three-dimensional
      distribution and structure of elastic fiber and laminae using the confocal laser
      scanning microscope was evaluated and also produced excellent results. used to
      discriminate calcified bone and elastic fibers using the fluorescence microscope
      (Bradbeer et al. 1994). The selective fluorescence exhibited by these two main
      tissue components is based on the very faint eosin staining, while intensely
      eosinophilic substrates and those stained with the highly absorbing basic dyes
      show no fluorescence or just a very faint signal. Considering the possibility of
      using eosin fluorescence for the selective identification of some tissue
      components, we have extended this approach to the study of elastic fibers in
      hematoxylin-eosin (H&E) preparations. This paper then describes the results of
      observations with the fluorescence microscope of some H&E stained sections and
      evaluates the use of the confocal laser scanning microscope to image elastic
      fibers in the same preparations. Furthermore, we have also studied absorption and
      fluorescence spectra of eosin and phloxine, a closely related dye, in solution,
      to correlate them with the fluorescence detected in tissue sections.

PMID- 8985748
TI  - Lipopolysaccharide-induced cytokine production in peripheral blood mononuclear
      cells: intracellular localization of tumor necrosis factor alpha and interleukin
      1 beta detected with a three-color immunofluorescence technique.
AB  - Lipopolysaccharide (LPS) can induce monocytes to produce various cytokines such
      as tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta). In
      the present study, the kinetics of both intracellular and extracellular
      accumulation of TNF alpha and IL-1 beta in LPS stimulated mononuclear cell (MNC)
      cultures has been determined. A three-color-immunofluorescence technique was used
      to detect intracellular accumulation of cytokines. Intracellular accumulation of
      TNF alpha in monocytes starts shortly after initiation of the culture; i.e., TNF
      alpha is detectable after 1 h, reaching a peak level after 3-4 hours with 50-65%
      of monocytes staining positive. In parallel with its increased intracellular
      presence, TNF alpha was also found in the culture supernatant. The intracellular
      accumulation of IL-1 beta in monocytes became detectable after 2 h of culture in
      the presence of LPS. After 4 h, a plateau was reached, with 90% of the monocytes
      being positive. In parallel, but with a little delay, IL-1 beta could be detected
      in the culture supernatant. TNF alpha and IL-1 beta can be produced
      simultaneously in the same monocytes as was shown by a three-color
      immunofluorescence technique. It is concluded that TNF alpha and IL-1 beta are
      good parameters for the early measurement of monocyte activation and that both
      the intracellular accumulation in monocytes and the amount of secreted cytokines
      can be used for such a purpose. The intracellular accumulation in monocytes can
      be measured by the three-color-immunofluorescence technique described.

PMID- 8985749
TI  - Is the lectin binding pattern of human breast and colon cancer cells influenced
      by modulators of sialic acid metabolism?
AB  - Sialic acid residues are the most abundant terminal carbohydrate residues of
      mammalian cells. Modification of the sialic acid residues by exposure of cells in
      culture to sialic acid precursor analogues resulted in a modified susceptibility
      to polyoma viruses. In the present study, human breast and colon cancer cell
      lines were exposed for 65 h to these acid precursor analogues at 5 mM and their
      lectin binding pattern was analysed. Use of a panel of several different lectins
      indicated that the pretreatment of these cell lines with the sialic acid
      analogues did not change their lectin binding profile. The incorporation of these
      precursors into membrane glycoproteins was assessed by reversed phase high
      performance liquid chromatography, which clearly demonstrated that the precursors
      were incorporated. The results therefore indicate that these analogues are highly
      specific for sialic acid and do not interfere with other biosynthetic pathways of
      membrane glycoconjugates.

PMID- 8985750
TI  - Specificity analysis of murine monoclonal antibodies reactive with Tn, sialylated
      Tn, T, and monosialylated (2-->6) T antigens.
AB  - T, Tn, and sialyated Tn (sTn) are pancarcinoma antigens, and increased expression
      of these carbohydrate epitopes has been correlated with a poor prognosis in
      several epithelial malignancies. Ten murine monoclonal antibodies have been
      generated to these antigens, and compared by ELISA and immunohistochemistry to
      established mAbs reactive with these antigens. Nine mAbs (3 IgM and 6 IgG)
      reactive with synthetic T-human serum albumin (T-HSA) were produced after
      immunizing BALB/c mice with a synthetic T-keyhole limpet hemocyanin
      glycoconjugate (T-KLH). An additional IgM mAb (145.22) was produced in mice
      immunized with erythrocytes isolated from a patient with Tn syndrome. Three IgM
      and six IgG1 mAbs reactive with T-HSA did not react with natural T antigen
      present on desialyated glycophorin. All three IgM and several IgG1 mAbs, however,
      did react with LS-174T, a mucinous colon carcinoma cell line, 647V, a human
      bladder carcinoma cell line, and TA3Ha, a murine mammary carcinoma cell line as
      well as fresh frozen colon carcinomas. MAb 145.22 reacted with both natural and
      synthetic sources of sTn and Tn, as well as with LS-174T cells and mucin deposits
      in 10/11 colon carcinomas on fresh-frozen sections. MAb B72.3 reacted strongly
      with ovine submaxillary mucin (OSM) and sTn-HSA, while mAb CC49, a second
      generation mAb to TAG-72 carcinoma mucin, reacted strongly with OSM, less
      strongly with desialyated OSM, and only weakly with sTn-HSA, suggesting that the
      epitope specificity for mAb CC49 is distinct from that of B72.3.

PMID- 8985751
TI  - Monoclonal antibody specific to bovine lens epithelial cell membrane: preparation
      of a lens epithelial cell-selective immunotoxin.
AB  - The lens opacity directly decreases visual acuity. To date, neither prophylactic
      nor pharmacologic treatments have been effective in stopping or decreasing lens
      opacity. Although extracapsular cataract extraction followed by intraocular lens
      insertion is considered to be an effective treatment, postoperative proliferation
      of lens epithelial cells (LECs) disturbs the vision again. In the present study a
      monoclonal antibody (MAb) directed against bovine LECs was generated. The MAb
      (XC3-2-B1H9) reacted specifically with the cell membrane of LECs. No other
      tissues in bovine eyes, such as the cornea, iris, ciliary body, choroid, retina,
      or the sclera, or any other major bovine organs, such as lung, liver, spleen, and
      kidney, were associated. The specificity of XC3-2-B1H9 was confirmed both by
      immunohistochemistry and by immunoblotting. This MAb cross-reacts with dog LECs.
      Based on immunoblot analysis, XC3-2-B1H9 recognizes the band with a Mr of about
      160 kD of the water-insoluble fraction of LECs. The subclass of these MAbs is
      IgG1 as determined by immunodiffusion. This MAb has the capacity to act as a
      component of an immunotoxin to target the LECs.

PMID- 8985753
TI  - Comparison of several mouse and rat monoclonal antibodies against human
      fibrinogen.
AB  - Six monoclonal antibodies raised against human fibrinogen have been
      characterized. Mouse monoclonal antibodies were targeted against sequential
      epitopes on the immunodominant D-domain of fibrinogen and they crossreacted with
      all molecules containing the D-domain [fibrin, fibrin(ogen)-degradation
      products]. Their behavior was not influenced by proteolytic degradation of
      fibrinogen with plasmin. Rat MoAbs were specific for the conformational epitopes
      on intact fibrinogen. Their reactivities were substantially lower with
      fibrin(ogen)-degradation products. Degradation of structures on intact fibrinogen
      was concomitant with the decay of rat MoAbs reactivity. Those structures were
      presumably on the C-terminal end of fibrinogen alpha chain and/or on the N
      terminal end of fibrinogen beta chain.

PMID- 8985754
TI  - Characterization of monoclonal antibodies to the 26-kDa glutathione S-transferase
      of Schistosoma japonicum.
AB  - Six monoclonal antibodies (MAbs) were raised in mice against the 26-kDa
      glutathione S-transferase (GST) of the parasite Schistosoma japonicum. These MAbs
      were originally selected for their specific binding to the recombinant GST (r
      GST) generated in E. coli by an enzyme-linked immunosorbent assay. A further
      study demonstrated that all these MAbs bound to plate-coated GST affinity
      purified from the parasite Schistosoma japonicum. However, in Western blotting
      analysis only a single monoclonal antibody (MAb Y3D7) yielded positive binding.
      The binding of MAb Y3D7 on Western blotting was further characterized; specific
      binding was found on other GST fusion proteins and on the authentic 26-kDa GST
      but not the 28-kDa GST in the total soluble worm proteins from Schistosoma
      japonicum. Using protein-A-mediated immunoprecipitation, MAbs Y3D7 and Y5D5
      precipitated r-GST while in parallel experiments the remaining MAbs did not
      generate r-GST precipitation. In an alternative co-precipitation experiment, r
      GST was first bound to glutathione (GSH) Sepharose beads and subsequently tested
      for interaction with the MAbs. In this manner, all MAbs except MAb Y5D5 were co
      precipitated with the complexes. Thus, these select MAbs readily reacted with GST
      although their binding characteristics were different. Because GST has been
      widely used in the generation of fusion proteins for various purposes and is a
      potential vaccine candidate in controlling schistosomiasis, these MAbs should
      prove valuable for their application to molecular biology and parasitology.

PMID- 8985752
TI  - Monoclonal antibodies against the 43,000 Da glycoprotein from Paracoccidioides
      brasiliensis modulate laminin-mediated fungal adhesion to epithelial cells and
      pathogenesis.
AB  - The surface glycoprotein gp43, a highly immunogenic component of Paracoccidioides
      brasiliensis, is used in the serodiagnosis of paracoccidioidomycosis (PCM) and
      has recently been shown to specifically bind the extracellular matrix protein
      laminin. Binding to laminin induces the increased adhesion of the fungus to
      epithelial cells; a hamster testicle infection model has shown that the gp43
      dependent binding of fungal cells to laminin enhances their pathogenicity in
      vivo. We report on the production and characterization of 12 monoclonal
      antibodies against the gp43 that recognize peptide sequences in the molecule
      detecting at least three different epitopes as well as different isoforms of this
      antigen. MAbs interfered in the fungal pathogenicity in vivo either by inhibiting
      or enhancing granuloma formation and tissue destruction. Results suggest that P.
      brasiliensis propagules may start infection in man by strongly adhering to human
      lung cells. Thus, laminin-mediated fungal adhesion to human lung carcinoma (A549)
      cells was much more intense than to Madin-Darby canine kidney cells (MDCK),
      indicating differences in binding affinity. Subsequent growth of fungi bound to
      the lung cells could induce the granulomatous inflammatory reaction
      characteristic of PCM. Both steps are greatly stimulated by laminin binding in
      infective cells expressing gp43.

PMID- 8985755
TI  - Generation and characterization of a humanized antibody with specificity for
      preS2 surface antigen of hepatitis B virus.
AB  - For the prevention of hepatitis B virus (HBV) infection, monoclonal antibodies
      (mAbs) against the surface antigens of HBV would offer several advantages over
      the current human polyclonal antibody. We have developed a humanized antibody
      with specificity for the preS2 surface antigen of HBV and evaluated the
      neutralizing activity of the humanized antibody. The complementarity-determining
      regions of the heavy and light chains of a murine monoclonal antibody (H8) were
      grafted onto the variable regions of a highly homologous human anti-Sm antibody,
      which were then combined with the constant regions of human gamma 1 and kappa,
      respectively. The affinity of the resulting humanized antibody (Z6B) was about
      one tenth that of the chimeric antibody. The new version (ZP39) of the humanized
      antibody, which was constructed by substituting the heavy-chain framework residue
      at position 94 of the Z6B with original mouse residue, showed almost the same
      affinity as that of the chimeric antibody. The evaluation of the HBV neutralizing
      activity of ZP39 using in vitro infection of adult human hepatocyte primary
      culture by HBV showed that it had a specific activity that was approximately 1000
      times higher than commercially available polyclonal hepatitis B immune globulin.
      We expect that the present humanized antibody will be useful in the prevention of
      HBV infection.

PMID- 8985756
TI  - Limited field evaluation of a rapid monoclonal antibody-based dipstick assay for
      urinary schistosomiasis.
AB  - A rapid, visually read monoclonal antibody (MoAb)-based dipstick assay for
      specific diagnosis of urinary schistosomiasis was field tested with microscopy
      and the use of hematuria and proteinuria in a schistosomiasis hematobia endemic
      area in Southern Ghana. The study group consisted of 229 individuals (114 males
      and 115 females) aged 1 to 86 years; 145/229 (63.3%) of the subjects submitted
      stool samples from which no S. mansoni eggs were detected. However, infections
      with Necator americanus (hookworms) 33.1%, Ascaris lumbricoides 2.8%, Trichuris
      trichiura (whipworm) 2.8%, and Strongyloides stercoralis 0.7% were detected but
      did not appear to influence the results of the MoAb-dipstick assay. Urinary
      schistosomiasis prevalence was estimated as 47.6% by microscopy, 48% by MoAb
      dipstick, 39.7% by microhematuria, and 23.6% by proteinuria. The MoAb-dipstick
      correctly identified 108/109 (99.1%) of microscopically confirmed cases and
      118/120 (98.3%) of egg-negative individuals, thereby giving a sensitivity of
      99.1% and a specificity of 98.3%. On the other hand, microhematuria and
      proteinuria were, respectively, 76.1% and 40.4% sensitive, and 94.2% and 92.5%
      specific when compared to microscopy. Microhematuria and proteinuria had
      significantly lower sensitivity (P < 0.001) than either microscopy or dipstick.

PMID- 8985757
TI  - Online services.

PMID- 8985758
TI  - Long-term survival of vancomycin-resistant Enterococcus faecium on a contaminated
      surface.

PMID- 8985759
TI  - Bloodstream infection from a Port-A-Cath: successful treatment with the
      antibiotic lock technique.

PMID- 8985760
TI  - Comparison of a rapid readout biological indicator for steam sterilization with
      four conventional biological indicators and five chemical indicators.

PMID- 8985761
TI  - Vancomycin use in a university medical center: comparison with hospital infection
      control practices advisory committee guidelines.

PMID- 8985762
TI  - Preventing staphylococcal infections by eradicating nasal carriage of
      Staphylococcus aureus: proceeding with caution.

PMID- 8985763
TI  - Reduction of surgical-site infections in cardiothoracic surgery by elimination of
      nasal carriage of Staphylococcus aureus.
AB  - OBJECTIVE: To test the hypothesis that perioperative elimination of nasal
      carriage of Staphylococcus aureus using mupirocin nasal ointment reduces the
      surgical-site infection (SSI) rate in cardiothoracic surgery. DESIGN: Unblinded
      intervention trial with historical controls. SETTING: A university hospital,
      tertiary referral center for cardiothoracic surgery. PATIENTS: Consecutive
      patients undergoing cardiothoracic surgery between August 1, 1989, and February
      1, 1991 (historical control group), and between March 1, 1991, and August 1, 1992
      (intervention group). RESULTS: The historical control group consisted of 928
      patients and the intervention group of 868, of whom 752 actually were treated.
      The 116 patients who were unintentionally not treated were considered as a
      concurrent control group. In the intention-to-treat analysis, a significant
      reduction in SSI rate was observed after the intervention (historical-control
      group 7.3% and intervention group 2.8%; P < .0001). The SSI rate in the
      concurrent control group was significantly higher than in the treated group (7.8%
      and 2.0%, respectively; P = .0023). Resistance of S aureus to mupirocin was not
      observed. CONCLUSION: The results of this study indicate that perioperative
      elimination of nasal carriage using mupirocin nasal ointment significantly
      reduces the SSI rate in cardiothoracic surgery patients and warrants a
      prospective, randomized, placebo-controlled efficacy trial. This preventive
      measure may be beneficial in other categories of surgical patients as well.

PMID- 8985764
TI  - Cost-effectiveness of perioperative mupirocin nasal ointment in cardiothoracic
      surgery.
AB  - OBJECTIVE: To assess the cost-effectiveness of perioperative intranasal
      application of mupirocin calcium ointment in cardiothoracic surgery. DESIGN: Cost
      effectiveness analysis based on results of an intervention study with historical
      controls. SETTING: University Hospital Rotterdam, a tertiary referral center for
      cardiac and pulmonary surgery. PATIENTS: Consecutive patients undergoing
      cardiothoracic surgery between August 1, 1989, and February 1, 1991 (control
      group, n = 928), and between March 1, 1991, and August 1, 1992 (intervention
      group, n = 868). INTERVENTION: Perioperative nasal application of mupirocin
      calcium ointment started on the day before surgery, continued for 5 days, twice
      daily. RESULTS: Postoperative costs were increased significantly in patients with
      a surgical-site infection (SSI), compared with uninfected patients (P < .001).
      Mean SSI-attributable costs were estimated at $16,878 (95% confidence interval,
      $15,575-$18,181). The incidence of SSIs was 7.3% in the control group and 2.8% in
      the intervention group, mupirocin effectiveness being 62%. The costs of mupirocin
      were $11 per patient. Thus, the savings per SSI prevented were $16,633. To
      validate this comparative estimate of SSI-attributable costs, a noncomparative
      analysis of the postoperative length of stay (POLS) was performed, according to
      the Appropriateness Evaluation Protocol. Approximately 50% of the comparative SSI
      attributable POLS were judged SSI-attributable in the noncomparative analysis.
      Sensitivity analyses, testing for the robustness of our conclusions, indicated
      that the presented model is rather insensitive to variations in the incidence of
      SSIs and for the effectiveness and costs of mupirocin. SSI-attributable costs
      were shown to be the only variable with substantial effect on the cost
      effectiveness ratio. Perioperative mupirocin would result in net costs instead of
      savings only if SSI-attributable costs were less than $245. CONCLUSIONS: SSIs in
      patients undergoing cardiothoracic surgery are associated with a substantial
      increase in postoperative costs. Provided that perioperative mupirocin reduces
      the SSI rate, this measure will be highly cost-effective in most centers
      providing cardiothoracic surgical services.

PMID- 8985765
TI  - Elimination of nasal carriage of Staphylococcus aureus in hemodialysis patients.
AB  - OBJECTIVE: To study the efficacy of mupirocin for the elimination of nasal
      carriage of Staphylococcus aureus in hemodialysis patients. DESIGN: The efficacy
      of mupirocin was studied in a prospectively followed cohort. The effect of this
      intervention on the rate of S aureus bacteremia was evaluated using a historic
      control group. SETTING: Patients on the hemodialysis unit of the University
      Hospital Rotterdam, a tertiary referral center. PATIENTS: The study group
      consisted of consecutive patients on hemodialysis from February 1, 1992, until
      November 1, 1993. They were screened by taking nasal cultures monthly during
      their time on hemodialysis. If S aureus was isolated, treatment with mupirocin
      nasal ointment was initiated. The control group consisted of patients treated on
      the same hemodialysis unit from January 1, 1990, until January 1, 1992. RESULTS:
      The study group consisted of 226 patients, of whom 172 were evaluated to
      determine the efficacy of mupirocin. Sixty-seven (39%) were identified as nasal
      carriers. Following the initial treatment, 66 nasal cultures (98.5%) became
      negative. After 3 months and 6 months, respectively, 63 (94%) and 61 (91%) of the
      treated carriers had negative cultures. The rate of bacteremia (defined as the
      number of episodes of S aureus bacteremia per patient-year on hemodialysis) was
      significantly lower among the 226 patients in the study group (0.04 per patient
      year) than among the 273 patients in the control group (0.25 per patient year, P
      < .001). Development of resistance and adverse effects were not observed.
      CONCLUSIONS: Mupirocin nasal ointment effectively eliminates nasal carriage of S
      aureus in patients on hemodialysis. This was associated with a significant
      reduction of the incidence of S aureus bacteremia, as compared to historic
      controls.

PMID- 8985766
TI  - A prolonged outbreak of methicillin-resistant Staphylococcus aureus in the burn
      unit of a tertiary medical center.
AB  - OBJECTIVE: To report an outbreak of methicillin-resistant Staphylococcus aureus
      (MRSA) in our burn unit and the steps we used to eradicate the organism. DESIGN
      AND SETTING: Outbreak investigation in the burn unit of a 900-bed tertiary-care
      medical center. OUTBREAK: Between March and June 1993, MRSA was isolated from 10
      patients in our burn unit. All isolates had identical antibiograms and
      chromosomal DNA patterns. CONTROL MEASURES: Infection control personnel
      encouraged healthcare workers to wash their hands after each patients contact.
      The unit cohorted all infected or colonized patients, placed each affected
      patient in isolation, and, if possible, transferred the patient to another unit.
      Despite these measures, new cases occurred. Infection control personnel obtained
      nares cultures from 56 healthcare workers, 3 of whom carried the epidemic MRSA
      strain. One healthcare worker cared for six affected patients, and one cared for
      five patients. We treated the three healthcare workers with mupirocin.
      Subsequently, no additional patients became colonized or infected with the
      epidemic MRSA strain. CONCLUSIONS: The outbreak ended after we treated healthcare
      workers who carried the epidemic strain with mupirocin. This approach is not
      appropriate in all settings. However, we felt it was justified in this case
      because of a persistent problem after less intrusive measures.

PMID- 8985767
TI  - Randomized prospective study of the impact of three needleless intravenous
      systems on needlestick injury rates.
AB  - OBJECTIVE: To determine the impact of three needleless intravenous systems on
      needlestick injury rates. DESIGN: Randomized controlled trial. SETTING: 1,000-bed
      tertiary-care Midwestern hospital. PARTICIPANTS: Nursing personnel from general
      medical, general surgical, and intensive-care units. INTERVENTIONS: From June
      1992 through March 1994, a metal blunt cannula (MBC), two-way valve (2-way), and
      plastic blunt cannula (PBC) were introduced into three study areas, and
      needlestick injury rates were compared to three control areas using traditional
      needled devices. RESULTS: 24 and 29 needlestick injuries were reported in study
      and control areas. Intravenous-therapy-related injuries comprised 45.8% and 57.1%
      of injuries in each area. Thirty-seven percent and 20.7% of study and control
      area needlestick injuries were considered to pose a high risk of bloodborne
      infection. The 2-way group had similar rates of total and intravenous-related
      needlestick injuries compared to control groups. The PBC group had lower rates of
      total and intravenous-related needlestick injuries per 1,000 patient-days (rate
      ratios [RR], 0.32 and 0.24; 95% confidence intervals [CI95], 0.12-0.81 and 0.09
      0.61; P = .02 and P = .003, respectively) and per 1,000 productive hours worked
      (RR, 0.11 and 0.08; CI95, 0.01-0.92 and 0.01-0.69; P = .03 and P = .005,
      respectively) compared to controls. CONCLUSIONS: Needlestick injuries continued
      in study areas despite the introduction of needleless devices, and risks of
      bloodborne pathogen transmission were similar to control areas. The PBC device
      group noted lower rates of needlestick injuries compared to controls, but there
      were problems with product acceptance, correct product use, and continued
      traditional device use in study areas. Low needlestick injury rates make
      interpretations difficult. Further studies of safety devices are needed and
      should attempt greater control of worker behavior to aid interpretation.

PMID- 8985768
TI  - Nasal and cutaneous carriage of Staphylococcus aureus in hemodialysis patients:
      the effect of nasal mupirocin.
AB  - Fifteen of 20 hemodialysis patients who carried Staphylococcus aureus in their
      nares also carried the organism on their hands; 2 of 20 patients who did not
      carry S aureus in their nares carried S aureus on their hands (P < .001). Eighty
      seven percent of patients who carried S aureus in their nares and on their hands
      carried the same strain at both sites. Intranasal mupirocin eliminated S aureus
      from both sites.

PMID- 8985769
TI  - Development of mupirocin resistance among methicillin-resistant Staphylococcus
      aureus after widespread use of nasal mupirocin ointment.
AB  - All methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from
      colonized or infected patients in a 625-bed public teaching hospital during an
      epidemic, and for 3 years thereafter, underwent susceptibility testing to
      mupirocin. Mupirocin resistance among MRSA increased markedly over this period
      (1990, 2.7%; 1991, 8.0%; 1992, 61.5%; 1993, 65%) in association with increased
      use of mupirocin ointment as an adjunct to infection control measures.

PMID- 8985771
TI  - Follow-up evaluation of respiratory isolation rooms in 10 midwestern hospitals.
AB  - As a follow-up to a 1992 study or respiratory isolation, we studied compliance
      with recommendations for respiratory isolation through smokestick testing (1993)
      and surveys (1994). Effective negative pressure was demonstrated in 80 of 156
      rooms and was associated with the presence of anterooms (P < .001). The
      proportion of surveyed hospitals periodically testing isolation rooms increased
      from 0% (1992) to 30% (1993) to 100% (1994; P < .001).

PMID- 8985770
TI  - Emergence of high-level mupirocin resistance in methicillin-resistant
      Staphylococcus aureus isolated from Brazilian university hospitals.
AB  - Surveillance for methicillin-resistant Staphylococcus aureus (MRSA) was
      implemented in Rio de Janeiro and Uberlandia University Hospitals, which had
      different policies on use of mupirocin. One hundred fourteen multiresistant MRSA
      strains were isolated from 62 patients. Mupirocin resistance was observed in 63%
      of strains in Rio de Janeiro, where there was extensive use of topical mupirocin,
      and 6.1% in Uberlandia, where its use was rare.

PMID- 8985772
TI  - Tuberculosis control in health care.
AB  - This article describes the basic framework for developing a tuberculosis (TB)
      control program. We suggest how to assess the risk of TB in a healthcare delivery
      setting, how to prioritize control measures based on their effectiveness, and how
      to meet current regulatory requirements. In addition, we discuss some problematic
      issues, examples of how other hospitals have confronted these issues, and where
      to obtain additional information on nosocomial TB.

PMID- 8985773
TI  - Breach in confidential AIDS patient information.

PMID- 8985774
TI  - Scanning electron microscopy shows inhibited gubernacular development in relation
      to undescended testes in oestrogen-treated mice.
AB  - The morphological relationship between transabdominal testicular descent and the
      'swelling reaction' of the gubernaculum was investigated in oestrogen-treated
      fetal mice by using scanning electron microscopy (scanning EM). In addition,
      flutamide was also administered to pregnant mice to determine whether androgens
      cause gubernacular growth and transabdominal testicular descent in offspring. In
      oestrogen-treated fetal mice, scanning EM showed that both the gubernacular
      'swelling reaction' and transabdominal testicular descent were inhibited, in
      addition to inhibition of Mullerian duct regression. The gubernaculum showed a
      flat, thin bulb (widest diameter 0.25 +/- 0.04 mm) and an elongated cord (1.28 +/
      0.41 mm) after oestrogen treatment in utero, which was significantly different
      in appearance from that in normal control mice (width 0.44 mm +/- 0.06 mm, p <
      0.001; length 0.27 +/- 0.19 mm, p < 0.0001). However, flutamide-treated mice
      showed much more normal gubernacular enlargement and transabdominal testicular
      descent. The width of the gubernacular bulb after flutamide exposure was 0.44 +/-
      0.05 mm, which was comparable to that in control animals; the length of the intra
      abdominal gubernaculum (0.44 +/- 0.15 mm) was slightly longer than in controls (p
      < 0.02). These results suggest that both the swelling reaction of the
      gubernaculum and transabdominal testicular migration are blocked by prenatal
      exposure to oestrogen. However, oestrogen exposure of the fetus does not block
      the swelling reaction of the gubernaculum by acting as an antiandrogen.

PMID- 8985775
TI  - Influence of Escherichia coli on motility parameters of human spermatozoa in
      vitro.
AB  - The influence of E. coli on human sperm motility was studied in vitro. Semen
      samples were prepared by a swim-up technique and adjusted to 22 x 10(6)
      spermatozoa/ml. Samples were then inoculated with different concentrations of a
      uropathogenic strain of E. coli, serotype 06, with initial sperm/bacteria ratios
      varying between 10:1 and 10000:1. Motion parameters were analysed by computer
      aided motility analysis directly, and 2, 4 and 6 h after inoculation. In a second
      series of experiments, bacterial replication was inhibited by addition of
      chloramphenicol. In a third series, the effect of E. coli culture filtrates on
      sperm motility was investigated. The direct inhibitory effect of E. coli on
      progressive motility of spermatozoa was found to depend upon the bacterial
      concentration. A distinct inhibitory effect was observed only at a sperm/bacteria
      ratio of approximately 1, achieved by growth of E. coli during the experiments.
      For modality of motion, no distinct changes were observed. When growth of
      bacteria was prevented by chloramphenicol, no inhibitory effect on sperm motility
      was detected. Sperm motility was not inhibited by E. coli culture filtrates.
      Analysis by electron microscopy revealed multiple adhesions of E. coli to
      spermatozoa, causing variable ultrastructural damage as probable morphological
      correlates of immobilization.

PMID- 8985777
TI  - Viability of ram spermatozoa in relation to the abstinence period and successive
      ejaculations.
AB  - For successful fertilization, a functionally constituted sperm plasma membrane is
      necessary, and this is clearly dependent on the sperm maturation process. The
      latter involves a series of complex changes which result from a sequence of
      events occurring at different points within the epididymis. The transit time
      through the epididymis can be influenced by external factors such as sexual
      stimulus and ejaculatory frequency. The present work was undertaken to determine
      changes in ram sperm viability and other sperm quality characteristics in
      relation to ejaculatory frequency. Three successive ejaculates were collected
      from rams during three different abstinence periods (collected every day, every 2
      days and every 3 days). Cell viability (membrane integrity determined by
      fluorescence staining), progressive individual motility, and other in vitro
      parameters of sperm quality were evaluated. Second ejaculates showed the highest
      cell viability of the three periods studied, and increased as the abstinence
      period lengthened. The maximum proportion of viable cells (average 60%) was
      obtained in the second ejaculate after an abstinence period of 3 days. Likewise,
      overall and progressive individual motilities were higher in second ejaculates,
      the maximum value being 70% after 3 days of abstinence. The percentage of damaged
      or acrosome-reacted spermatozoa was greater after 1 day of abstinence than after
      the other periods analysed, whereas the first ejaculate showed the highest value
      in all periods. Differences in ejaculate volume were correlated strongly with
      both variables considered (abstinence period and ejaculate number). In the third
      ejaculate, about 27% more volume was obtained after 3 days of abstinence than
      after abstinence for 1 or 2 days. Sperm concentration increased significantly as
      the abstinence period lengthened, and also decreased significantly with ejaculate
      number in all cases. Therefore, the total number of spermatozoa in the ejaculate
      was clearly dependent on the abstinence period and the ejaculate number. In
      conclusion, the results obtained suggest that using the second and/or a mixture
      of second and third ejaculates would improve the results in artificial
      insemination and in fertility studies. In addition, the use of better quality
      semen would facilitate progress in semen cryopreservation studies.

PMID- 8985776
TI  - Epididymal oxytocin in the rat: its origin and regulation.
AB  - Oxytocin is localized to the Leydig cells of the testis in the rat and several
      other species where it is postulated to play a role in steroidogenesis and
      seminiferous tubule contractility. Oxytocin has also been detected in the
      epididymis of the ram where active uptake of the peptide from luminal fluid has
      been demonstrated. This study was performed to investigate whether oxytocin is
      present in the rat epididymis, and the origin of the peptide. Immunoactive
      oxytocin was detected in the epididymis of all control animals examined (147.7 +/
      41.7 pg/g). Total epididymal oxytocin was reduced significantly following
      castration (p < 0.05). Testosterone treatment also reduced the epididymal
      concentration of the peptide in both intact and castrated rats. Efferent duct
      ligation (EDL) did not affect the presence of oxytocin in the epididymis.
      Immunoactive oxytocin was localized in discrete cells of the epithelium of the
      caput epididymis, with less staining apparent in the initial segment and cauda
      epididymis. Staining disappeared from the caput epididymis following castration,
      but reappeared following testosterone supplementation. No obvious alteration in
      staining was observed in the cauda epididymis after EDL. These data demonstrate
      for the first time the presence of oxytocin in the epididymis of the rat and that
      the peptide may be regulated by androgens. They further suggest an epididymal
      source of the peptide.

PMID- 8985778
TI  - Treatment with human chorionic gonadotrophin for cryptorchidism: clinical and
      histological effects.
AB  - The efficacy of hCG treatment was studied in 182 cryptorchid patients. The
      efficacy of the treatment correlated with the initial position of the testis.
      None of the abdominal testes reached a normal position, whereas 90% of high
      scrotal testes descended during the treatment. Fifty-four boys who were treated
      unsuccessfully with hCG and 29 untreated boys were biopsied. The biopsies were
      performed on 32 scrotal and 87 maldescended testes to examine the state of the
      organ and the effects of hCG treatment. In biopsies, the volume densities of
      seminiferous tubules, interstitial tissue and blood vessels were counted, and the
      sections screened for interstitial bleeding. Significant differences between
      scrotal and maldescended testes were found in all of the volume densities
      measured. Interstitial bleeding occurred rarely in scrotal testes, whereas in
      maldescended testes it was frequently apparent. hCG treatment induced a
      significant increase in the volume density of both interstitial tissue and blood
      vessels. Even though the hCG treatment induced measurable, possibly harmful,
      changes both in scrotal and maldescended testes, our data do not prove that hCG
      treatment causes permanent damage to the testis.

PMID- 8985779
TI  - Structure of small blood vessels in the testes of infertile men.
AB  - In the testis, 'hyalinization' of the lamina propria of seminiferous tubules is
      often accompanied by similar changes within the walls of testicular blood
      vessels. The aim of our study was to investigate the structure of small blood
      vessels in hyalinized human testes by means of immunohistochemistry, electron
      microscopy and image analysis methods. Results of immunohistochemical analysis
      indicated that, despite hyalinization, testicular small blood vessels retained
      positive immunostaining for desmin and actin. Their basement membranes remained
      immunopositive for collagen IV and laminin. No proliferative (Ki-67) activity was
      observed in the blood vessel walls in testes from both control and infertile men.
      P-170 glycoprotein was found to be expressed only in primary spermatocytes. No
      difference in expression and localization of this antigen was observed between
      control and affected testes. Electron microscopy revealed a number of testicular
      arterioles with a notably narrow lumen due to enlarged endothelial cells in
      infertile men. Such arterioles also had a thickened subendothelial layer and an
      abundant tunica adventitia rich in connective tissue fibres and ground substance.
      Some venules in hyalinized testes displayed increased connective fibres and
      ground substance in the subendothelial layer, between the smooth muscle cells of
      the tunica media and the tunica adventitia. However, no changes were found in the
      capillary network, when compared to controls. Image analysis data showed a
      statistically significant increase in the surface of tunica intima and adventitia
      of arterioles and tunica media of venules. It is concluded that hyalinization
      mostly affects testicular arterioles and venules, but not capillaries. Our
      immunohistochemical data indicate that the 'nature' and/or extent of
      hyalinization in testicular small blood vessels differs from that described
      previously for the lamina propria of seminiferous tubules.

PMID- 8985780
TI  - Anxiety-induced failure in erectile response to intracorporeal prostaglandin-E1
      in non-organic male impotence: a new diagnostic approach.
AB  - Intracavernous injection (ICI) of prostaglandin-E1 (PGE1) is used widely as the
      first diagnostic test in the study of erectile dysfunction. However, a lack of
      full erection after a maximal dose is frequent. As well as vascular incompetence,
      this may be due to stress-induced changes, related to the ICI procedure. The aim
      of this study was to investigate the influence of emotional disturbances on
      erectile response to ICI in impotent patients. Initially, 24 young men with non
      organic impotence (age 34.6 +/- 1.5 years; mean +/- SEM) were selected and
      randomized single-blind to pharmacoerection with PGE1 alone (20 micrograms/mL) or
      a mixture (cocktail) containing 20 micrograms PGE1 plus an alpha-adrenergic
      receptor blocker, phentolamine (Phe, 0.5 mg/mL). Additional studies were also
      performed double-blind on 10 men with non-organic impotence (age 37.6 +/- 1.2
      years) utilizing higher PGE1 dosages for ICI (25 micrograms/mL alone or in
      combination with Phe, 0.5 mg/mL). After a 7-day interval, all subjects were
      crossed-over to receive the alternative treatment. The presence of emotional
      disturbances was assessed in all patients by the administration of rapid tests
      (Stai-X1 and Stai-X1r for state-anxiety before and after ICI, respectively; Stai
      X2 for trait-anxiety; Zung-test for depression) at the first and at the remaining
      (Stai-X1 and Stai-X1r) ICI sessions. ICI with 20 and 25 micrograms/mL PGE1 led to
      a comparable percentage of patients who reported a valid-for-intromission (VFI)
      erection (63 and 60%, respectively). In contrast, use of the cocktails
      significantly increased the percentage of subjects with a VFI (87 and 90% of the
      total number of patients tested, respectively; p < 0.05). Moreover, a strong
      inverse correlation between state-anxiety scores (Stai-X1) and the erectile
      response to ICI with 20 and 25 micrograms PGE1 was found (r = -0.69, p < 0.001);
      such a correlation was not present in patients who underwent ICI with the
      cocktails. Two cases of prolonged erection occurred (one after 20 micrograms PGE1
      and the other after 20 micrograms PGE1 plus Phe) which were reversed promptly by
      the intracavernous injection of metharaminol. It is concluded that the lack of a
      full erectile response after ICI with PGE1 can be related to the presence of a
      high 'state-anxiety' in the patients. In such patients, a VFI erectile response
      can be induced by the administration of a cocktail test-dose.

PMID- 8985781
TI  - Polymorphism in the cytochrome P450 2E1 gene and alcohol-induced disorders of
      human spermatogenesis.
AB  - The association between alcohol-induced disorders of human spermatogenesis and
      four restriction fragment polymorphisms (DraI, MspI, PstI and RsaI) of the
      cytochrome P450 2E1 gene was investigated in an autopsy study on 254 men.
      Acquaintances were interviewed and the mean daily alcohol consumption of the
      subjects was calculated on the basis of the interviews. Spermatogenesis score and
      testicular morphology were assessed by light-microscopy, and cytochrome 2E1
      polymorphic genotypes were determined using the polymerase chain reaction. Of the
      204 heavy-drinking men, 42 (20.6%) men had normal spermatogenesis (p < 0.001,
      compared to moderate drinkers). Partial spermatogenic arrest was observed in 76
      (37.3%) men and complete spermatogenic arrest in 79 (38.7%) men (p < 0.001,
      compared to moderate drinkers), whereas seven men (3.4%) had Sertoli cell only
      syndrome. The overall allelic frequencies for the common and rare polymorphic
      alleles were 0.98 and 0.02 (MspI) and 0.99 and 0.01 (PstI and RsaI),
      respectively. No associations between heterozygosity in the MspI, PstI or RsaI
      loci, or the allelic frequencies of common and rare alleles, and disorders of
      spermatogenesis were observed. The allelic frequencies for the common and rare
      polymorphic alleles in the DraI locus were 0.90 and 0.10, respectively. No
      significant difference was observed, either among moderate or heavy drinkers, in
      the frequency of the rare allele between men with disorders of spermatogenesis
      and those with normal spermatogenesis in the respective group, although men with
      disorders of spermatogenesis in general had a slightly lower frequency of the
      rare allele when compared to those with normal spermatogenesis. In conclusion, we
      were unable to demonstrate a significant association between any polymorphisms in
      the CYP2E1 gene and disorders of spermatogenesis. RsaI, MspI and PstI
      polymorphisms were extremely rare in our population and could thus possibly be
      excluded as reasons for genetic susceptibility to disorders of spermatogenesis in
      our series.

PMID- 8985782
TI  - Cyclic morphiceptin analogs: cyclization studies and opioid activities in vitro.
AB  - Attempts were undertaken to develop cyclic beta-casomorphin-5 analogs with
      improved opioid activity profiles by deletion of the glycine residue in position
      5, leading to analogs structurally related to the opioid peptide morphiceptin (H
      Tyr-Pro-Phe-Pro-NH2). The tetrapeptide sequence Boc-Tyr(tBu)-D-Xaa-Phe-Yaa-OH
      (Xaa = Lys, Orn, A2bu; Yaa = Pro in L- or D-configuration) was used to study the
      influence of ring size and chirality on the yield of cyclization between the
      omega-amino group of Xaa and the C-terminal carboxyl group. In all cases the
      cyclization reaction was performed under identical experimental conditions to
      allow a direct comparison with regard to yield and homogeneity. The reaction
      products were purified by crystallization and liquid chromatography, and were
      characterized by HPLC, TLC, electrospray mass spectrometry and 1H-NMR
      spectroscopy. In none of the reactions performed with the cyclization precursors
      containing proline in the L-configuration could a cyclic monomer be detected, and
      the cyclodimer (7-9) was the exclusive product in each case. Cyclodimerization
      was also the favored reaction in the attempted formation of the 11-membered ring
      of the cyclic [D-A2bu2, D-Pro4]-morphiceptin analog 12, since only traces of the
      monomer were found. In the case of both the [D-Lys2, D-Pro4]-analog 10 and the [D
      Orn2, D-Pro4]-analog 11, the cyclomonomer/cyclodimer ratio was about 80:20. The
      cyclic monomers 10 and 11 showed high opioid activity in the mu-receptor
      representative guinea pig ileum assay (IC50 = 2-5 nM) and in the delta-receptor
      representative mouse vas deferens assay (IC50 = 50-60 nM), whereas the potency of
      the cyclodimers was 2-3 orders of magnitude lower in both in vitro bioassays.

PMID- 8985783
TI  - Binding of human serum amyloid A (hSAA) and its high-density lipoprotein3 complex
      (hSAA-HDL3) to human neutrophils. Possible implication to the function of a
      protein of an unknown physiological role.
AB  - Serum amyloid A (SAA) is an acute-phase serum protein which exists in the body in
      a complex with high-density lipoprotein (HDL3). It is involved in chronic
      inflammation and neoplastic diseases in an as yet unknown manner. Toward an
      understanding of the possible physiological role of SAA we initiated a study of
      its association with blood proinflammatory cells with which it may interact
      functionally in vivo. In the following we describe the binding characteristics of
      recombinant human SAA to human neutrophils (polymorphonuclear leukocytes; PMNLs)
      and their plasma membranes. Scatchard analysis of rSAA binding and displacement
      curves revealed Kd in the nanomolar range. The C-terminal domain of the protein,
      i.e. amino acid residues 77-104, which might reside in serum following SAA
      degradation and amyloid A formation, was found to inhibit efficiently the binding
      of the whole protein to neutrophils. The interaction of SAA, and of its related
      peptides while complexed in HDL3, with human PMNs was also studied. The results
      suggest that SAA may be involved, in an as yet unknown manner, in the neutrophil
      associated inflammatory mechanism.

PMID- 8985784
TI  - Characterization of PO1, a new peptide ligand of the apamin-sensitive Ca2+
      activated K+ channel.
AB  - A new peptide ligand of the small conductance Ca2+ activated K+ channels has been
      purified from the venom (obtained by manual rather than electrical stimulation of
      the scorpion Androctonus mauretanicus mauretanicus), by following the inhibition
      of the 125I-apamin binding to its receptor on rat brain synaptosomes. Only one
      step on a C18 reversed-phase high-performance liquid chromatography column was
      necessary to obtain PO1. Its K0.5 for the apamin binding site was 100 nM. The
      amino acid sequence of PO1 is different from those of leiurotoxin and PO5. For
      the first time the same peptide was also purified from the venoms of two other
      species of North African scorpions, Androctonus australis and Buthus occitanus
      tunetanus. PO1 was chemically synthesized by the solid-phase technique and fully
      characterized. A model of PO1 was constructed by amino acid replacement using PO5
      nuclear magnetic resonance studies as the starting model. Structure-activity
      relationships between these toxins and their receptor are discussed.

PMID- 8985785
TI  - Alanine scan and N-methyl amide derivatives of Ac-bombesin[7-14]. Development of
      a proposed binding conformation at the neuromedin B (NMB) and gastrin releasing
      peptide (GRP) receptors.
AB  - Alanine and N-methylation scans together with molecular modelling were
      implemented in order to propose a binding conformation of the minimum active
      fragment of bombesin (BB), Ac-BB[7-14], to the gastrin releasing peptide (GRP)
      and neuromedin B (NMB) receptors. These data are also used to critically evaluate
      the previously proposed binding conformations such as alpha-helix and
      antiparallel beta-sheets. This shows that the previously reported conformations
      do not satisfy the experimental data. A new binding conformation of Ac-BB[7-14]
      is proposed consisting of three consecutive gamma-turns followed by a bend and
      finishing with two gamma-turns. This low energy conformation (analogous to a
      fragment of thymidylate synthase, 2TSC) of bombesin stabilized by five internal
      hydrogen bonds, and with the side chains of residues Trp8 and Leu13 held on the
      same side of the peptide, is in agreement with the experimentally observed data.
      This and the results of molecular modelling may aid in the synthesis of
      conformationally restricted high affinity bombesin analogues and/or high affinity
      template-based GRP or NMB receptor agonists and antagonists.

PMID- 8985786
TI  - Kinetics of inhibition of aminoacylase activity by dithiothreitol or 2
      mercaptoethanol.
AB  - The previously described kinetic method of the substrate reaction during
      irreversible inhibition of enzyme activity [Tsou (1988) Adv. Enzymol. Relat.
      Areas Mol. Biol. 61, 381-436] has been used to study the inactivation kinetics of
      aminoacylase by dithiothreitol (DTT) and 2-mercaptoethanol (MET). The results
      show that the inactivation of aminoacylase by DTT or MET is competitive slow
      reversible inhibition. The microscopic rate constants for the inactivation
      reaction were determined. Removal of these inhibitors by dialysis can lead to
      complete recovery of enzymatic activity. The present results also show that the
      presence of equimolar Zn2+ to DTT gives complete protection of the enzyme against
      the inactivation by DTT. Moreover, addition of equimolar amounts of Zn2+ to DTT
      can induce recovery of the enzymatic activity of DTT-inactivated enzyme. It is
      known that aminoacylase from pig kidney contains no disulfide bonds. Therefore,
      it may be suggested that inactivation of aminoacylase by dithiothreitol or 2
      mercaptoethanol is not due to the reduction of disulfide bonds, and is a
      competitive slow-reversible inhibition.

PMID- 8985787
TI  - NMR solution structure of the receptor binding domain of Pseudomonas aeruginosa
      pilin strain P1. Identification of a beta-turn.
AB  - The solution structure of the peptide antigen from the receptor binding domain of
      Pseudomonas aeruginosa strain P1 has been determined using two-dimensional 1H NMR
      techniques. Ensembles of solution conformations for the trans form of this 23
      residue disulfide bridged peptide have been generated using a simulated annealing
      procedure in conjunction with distance and torsion angle restraints derived from
      NMR data. Comparison of the NMR-derived solution structures of the P1 peptide
      with those previously determined for the 17-residue PAK, PAO and KB7 strain
      peptides [McInnes, C., et al. (1993) Biochemistry 32, 13432-13440; Campbell,
      A.P., et al. (1995) Biochemistry 34, 16255-16268] reveals the common structural
      motif of a beta-turn, which may be the necessary structural requirement for
      recognition of a common cell surface receptor and a common cross-reactive
      antibody to which all four strains bind. The importance of this conserved beta
      turn in the PAK, PAO, KB7 and P1 peptides is discussed with regard to the design
      of a synthetic peptide vaccine effective against multiple strains of Pseudomonas
      aeruginosa infections.

PMID- 8985788
TI  - Application of the allyloxycarbonyl protecting group for the indole of Trp in
      solid-phase peptide synthesis.
AB  - The synthesis and stability of allyloxycarbonyl (Aloc) indole-protected Trp
      derivatives and their application in solid-phase peptide synthesis are reported.
      The study shows that the Aloc protection on the indole moiety is suitable for
      orthogonal protection in the Fmoc/tBu strategy if the Fmoc group is cleaved with
      DBU. Several tryptophan-containing peptides have been synthesized including
      dynorphin A-(1-13), which has been intensively studied with respect to side
      reactions during the final TFA cleavage procedure. The results demonstrate the
      protective function of the Aloc group on the Trp during final deprotection.
      Furthermore, it could be demonstrated that Trp(Aloc)-containing peptides can be
      isolated and that the Aloc group can then be removed in a second step. The
      synthesis of phosphorylated delta sleep inducing peptide (P-DSIP) using the
      global phosphorylation approach provides another example in which Trp indole
      protection by Aloc prevents the formation of oxidative side products.

PMID- 8985789
TI  - Conformation of a water-soluble beta-sheet model peptide. A circular dichroism
      and Fourier-transform infrared spectroscopic study of double D-amino acid
      replacements.
AB  - Among peptide secondary structures beta-sheet domains have been much less
      intensively studied than alpha-helical conformations, mainly because of the lack
      of well characterized model peptides. In the present paper the secondary
      structure of a water-soluble de novo peptide consisting of 26 amino acids
      (DPKGDPKGVTVTVTVTVTGKGDPKPD-NH2) and the corresponding double D-amino acid
      replacement set have been studied by circular dichroism and Fourier-transform
      infrared spectroscopy. The model peptide was found to be unstructured in aqueous
      solution at peptide concentrations < 10(-3) mol/L but to adopt a predominantly
      beta-sheet structure in the presence of 15 mM sodium dodecyl sulfate or at
      apolar/water interfaces. Although the peptide is composed of amino acids with low
      helical propensity, it formed a single-stranded helical structure in aqueous
      trifluoroethanol. The D-amino acid replacement set was synthesized in order to
      study the conformational stability of the model peptide selectively in distinct
      regions. The data show that both the alpha-helix present in 50% trifluoroethanol
      as well as the beta-sheet domain formed in the presence of sodium dodecyl sulfate
      or at apolar/water interfaces, are located in the region between Val9 and Thr18.
      Pairwise substitution of adjacent amino acids by their corresponding D-amino
      acids provides a pronounced beta-sheet disturbance. These findings demonstrate
      that double D-amino acid replacements may be used to locate beta-sheet domains in
      peptides.

PMID- 8985790
TI  - Structure-activity relationship of the ring portion in backbone-cyclic C-terminal
      hexapeptide analogs of substance P. NMR and molecular dynamics.
AB  - The conformations of two backbone-cyclized substance P analogs were derived from
      homo- and heteronuclear NMR measurements and molecular dynamics simulations
      carried out in DMSO. The analogs contain subtle variations in the ring chemistry
      and are compared with biologically active analogs previously examined. The
      correlation between conformation and activity is used to gain insight into the
      conformational requirements from the pharmacophore.

PMID- 8985791
TI  - The use of the telephone in cardiac and pulmonary rehabilitation.

PMID- 8985792
TI  - American College of Sports Medicine Exercise Specialist Workshop/Certification. A
      modality for career preparation.

PMID- 8985793
TI  - Clinical applications of cardiopulmonary exercise testing.
AB  - Noninvasive measurement of metabolic and cardiorespiratory variables can be
      readily obtained using computerized systems as part of exercise testing of
      patients on a cycle ergometer or treadmill. The major indications for CPEX are:
      to assess exercise-related symptoms, especially dyspnea and chest pain; to
      measure exercise capacity including acceptability of patients with end-stage
      heart disease for cardiac transplantation; to evaluate for impairment/disability;
      to establish safety and guidelines for exercise training; and to assess response
      to specific therapy. As most patients with chronic cardiorespiratory disorders
      reduce their activities and consequently become deconditioned, CPEX should be
      considered as part of the initial evaluation. The results of CPEX should enable
      the physician to understand the reason(s) for the patient's exercise limitation
      and usually support the recommendation that the patient participate in a
      reconditioning or rehabilitation program. Should expired gases be measured as
      routine for all exercise tests? The use of CPEX depends on the clinical question.
      If the question is, "Does the patient have ischemic heart disease?", then a
      standard "cardiac stress test" is adequate. If the clinical question is, "Why is
      the individual limited in exercise ability?" or "Why is a patient breathless with
      activities?", then comprehensive CPEX is indicated. One important issue relating
      to CPEX is cost effectiveness. Do the results of CPEX justify the expense? There
      are little if any data to answer this question. However, if CPEX can establish a
      specific diagnosis, exclude significant heart disease, estimate work capacity,
      and/or provide guidelines for prescription of exercise intensity, this
      information may be invaluable to the individual patient and to the health-care
      provider. It is possible that CPEX may answer a specific clinical question and
      thereby actually eliminate the need and reduce the cost of additional expensive
      diagnostic tests. A prospective assessment of the cost effectiveness of CPEX will
      be important for select clinical problems.

PMID- 8985794
TI  - Responses to arm exercise in patients with compensated heart failure.
AB  - PURPOSE: This study compares the responses of 20 male patients (mean age 51 +/-
      11 years) with stable heart failure during peak and submaximal arm and leg
      exercise. METHODS: On day 1, subjects completed two symptom-limited graded
      exercise tests, one with their arms and one with their legs. On day 2, subjects
      performed arm only and leg only exercise at a matched power output of 30 Watts
      (W). Ten age-matched healthy subjects served as controls. RESULTS: During peak
      arm exercise power output, oxygen consumption (VO2), ventilation, and rate
      pressure product were higher in healthy subjects than in patients with heart
      failure. However, when a subject's peak VO2 or power output during arm exercise
      was expressed as a percentage of that achieved during peak leg exercise, no
      significant differences were noted between patients with heart failure and
      healthy subjects. Among both groups, rate-pressure product, VO2, ventilation, the
      ventilatory equivalent for O2, and respiratory exchange ratio were all higher
      when exercising at 30 W with the arms versus 30 W with the legs. Also, in
      patients with heart failure heart rate was higher (+6 min-1) and stroke volume
      index lower (-4 mL/m2) during submaximal arm than leg exercise. CONCLUSIONS:
      Although peak exercise capacity (Watts, VO2) during arm exercise is lower in
      patients with heart failure than healthy subjects, when expressed as a percentage
      of peak leg capacity, the extent of the exercise intolerance they experience
      during arm exercise does not differ from healthy subjects.

PMID- 8985795
TI  - The role of perceived overprotectiveness in recovery 3 months after myocardial
      infarction.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that
      overprotectiveness of patients after myocardial infarction (MI) by the spouse has
      a negative effect on recovery. METHODS: Subjects were 52 male patients who were
      admitted to one of four area hospitals with a first documented myocardial
      infarction (MI) and their wives. While in hospital, patients were interviewed by
      a research nurse who rated the patient's emotional distress on a scale from 1 to
      10. Patients completed a Family APGAR and a self-efficacy scale for cardiac
      patients estimating their level of functioning in 3 months. Wives also completed
      a Family APGAR, an estimate of their husbands' functioning in 3 months using the
      self-efficacy scale, and Zung Depression and Anxiety scales. At 3 months post-MI,
      patients completed the following questionnaires: Family APGAR, self-efficacy
      scale for cardiac patients regarding current functioning, Zung Anxiety and
      Depression scales, and the Psychosocial Adaptation to Illness Scale. Perceived
      overprotectiveness and criticism were measured using the Influential
      Relationships Questionnaire. The Goldman Specific Activity Scale was used to
      quantify cardiac recovery. Wives completed the same questionnaires as at the
      first assessment. RESULTS: Perceived overprotectiveness was positively correlated
      with patients' anxiety and depression, with perceived criticism from their wives,
      and correlated negatively with quality-of-life. However, it was not related to
      the patients' confidence in their functional abilities or to cardiac functional
      classification at 3 months. Wives who were perceived as overprotective had been
      less optimistic about their husbands' functional recovery immediately after the
      MI. Patients who perceived themselves to be overprotected at 3 months had also
      been less optimistic about their functional recovery when assessed a few days
      post-MI. CONCLUSIONS: Although perceived overprotectiveness is part of a negative
      emotional experience for the male patients, it does not appear to be related to
      perceived functional abilities or cardiac functional classification at 3 months
      post-MI. Whether the perceived overprotectiveness studied here is a function of
      the patient's overall emotional state or the wife's actual behavior or a
      combination of both is an area for future research.

PMID- 8985796
TI  - Oxygen uptake and its relation to physical activity and other coronary risk
      factors in asymptomatic middle-aged Japanese.
AB  - PURPOSE: Low physical activity is considered to be an important risk factor for
      atherosclerotic coronary artery disease. However, few data are reported on the
      Japanese general population. The authors have studied whether oxygen uptake in
      physical fitness evaluation is a quantitative index for physical activity and
      whether or not it has a relation to coronary risk factors. METHODS: Five hundred
      thirteen asymptomatic Japanese (40-64 years of age, 282 males and 231 females)
      were tested on a cycle ergometer for measurement of peak oxygen uptake (peak VO2)
      and oxygen uptake at anaerobic threshold (VO2AT). Physical activity was estimated
      by pedometer score. Data for oxygen uptake were adjusted by age or by age and
      body mass index (BMI), then its relationship to the following risk factors was
      investigated: physical activity, BMI, blood pressure, total cholesterol, HDL and
      LDL cholesterol, fasting blood glucose, and triglycerides. RESULTS: Subjects in
      the highest peak VO2 quartile walked significantly more than those in the lowest
      quartile in both males and females. Those in the highest quartile showed lower
      BMI, lower blood pressure, lower triglyceride, and higher HDL cholesterol. The
      same relationship was observed for VO2AT. CONCLUSIONS: Higher fitness level
      determined by peak VO2 or VO2AT is related to higher physical activity and lower
      coronary risk factors in the asymptomatic middle-aged Japanese. These data
      provide support for exercise prescription in the primary prevention of coronary
      heart disease in Japan.

PMID- 8985797
TI  - Feasibility and effects of a home-care rehabilitation program in patients with
      chronic obstructive pulmonary disease.
AB  - PURPOSE: Pulmonary rehabilitation programs often show beneficial effects in
      patients with chronic obstructive pulmonary disease (COPD). These programs are
      usually hospital-based. This study assesses the feasibility and application of a
      12-week Home-Care Rehabilitation Program (HCRP), carried out by general
      practitioners, physiotherapists, and home-care nurses. METHODS: Effects of the
      HCRP are assessed in 15 COPD patients with moderate to severe airflow limitation
      (inspiratory vital capacity [IVC]: mean, 75.4 [SD, 13.7] percent predicted, mean
      FEV1: 45.5 [6.9] percent predicted) and are compared with a stratified and
      randomized control group (n = 15). RESULTS: All participating disciplines judged
      the program to be useful and feasible. Patient compliance with the rehabilitation
      exercises was high. No major problems concerning the rehabilitation program were
      reported. After the HCRP, 4-minute walking distance improved significantly from
      274 m [61] to 301 m [72] and maximal work load (W max), as measured during an
      incremental cycle test, increased from 75.3 W [24] to 85.3 W [28]. At equal work
      levels (W submax) during the cycle test both Borg dyspnea and leg effort scores
      decreased significantly after the HCRP (6.7 [1.3] versus 4.9 [1.7] and 4.2 [2.0]
      versus 1.7 [2.5], respectively). Changes in walking distance, dyspnea, and leg
      effort scores at W submax were significantly different between the two groups.
      IVC and FEV1 did not change significantly. In the control group, no significant
      changes in any parameter were observed. CONCLUSION: It was possible to design and
      perform successfully a home-care rehabilitation program, providing both objective
      and subjective improvements in a group of patients with COPD. A home-care
      rehabilitation program appears to be a valuable component in the management of
      COPD patients with a moderate to severe airflow limitation.

PMID- 8985798
TI  - Estimating oxygen consumption during treadmill and arm ergometry activity in
      males with coronary artery disease.
AB  - PURPOSE: This study compared the accuracy of common clinical treadmill and arm
      ergometry equations in estimating the rate of oxygen consumption for males with
      coronary artery disease. METHODS: Measured and estimated submaximal and maximal
      oxygen consumption (VO2sub and VO2max) were compared during clinical treadmill
      (TM) and arm ergometry (AE) graded exercise tests in 15 males with established
      coronary artery disease (CAD). Estimated VO2sub and VO2max were derived from
      popular modality specific estimation equations, including those of the American
      College of Sports Medicine, Bruce and colleagues, Balady and colleagues, and
      Manfre and colleagues. RESULTS: The American College of Sports Medicine (ACSM)
      1991 TM equation overestimated VO2sub from 0.3 +/- 0.6 to 1 +/- 0.7 metabolic
      equivalents (METS) and VO2max by 3 +/- 3 METS, whereas the Bruce Normal Submax
      and Bruce Cardiac Submax equations inaccurately estimated VO2sub from -1 +/- 0.6
      to 0.9 +/- 0.7 METS. The Bruce Active Max and Bruce Sedentary Max equations
      overestimated VO2max from 1 +/- 2 to 2 +/- 2 METS, whereas the Bruce Cardiac Max
      equation accurately estimated oxygen consumption at maximal exercise. The ACSM
      and Manfre Healthy AE equations underestimated VO2sub at low and intermediate
      workloads from 0.4 +/- 0.4 to 0.8 +/- 0.4 METS. However, the Balady Male and
      Manfre Cardiac AE equations underestimated VO2 at each submaximal work load from
      0.6 +/- 0.3 to 1 +/- 0.6 METS and at maximal work loads from 0.8 +/- 0.9 to 2 +/-
      0.8 METS. The ACSM and Manfre Healthy AE equations accurately estimated VO2 at
      greater submaximal work loads and at maximal exercise. CONCLUSIONS: These data
      suggest that the ability to estimate VO2 in males with CAD is more accurately
      performed during nonweight-bearing arm activity, although the reason is not
      entirely understood, and significant inconsistencies exist in the ability to
      accurately estimate VO2 during treadmill exercise. These data further suggest
      concern regarding exercise prescription from estimated values derived from both
      treadmill and arm ergometry tests, because submaximal, and in some instances
      maximal, estimations were inaccurate. Future research should focus on the
      development of accurate estimations for those with CAD, primarily during
      submaximal work.

PMID- 8985800
TI  - Functional outcomes of patients on a rehabilitation unit after open heart
      surgery.
AB  - BACKGROUND: Compared with predecessors, the modern-day patient who undergoes
      cardiac surgery is sicker, is older, has more diffuse disease, has poorer
      ventricular function, and is more likely to be a repeat surgery. Patients
      hospitalized after open heart surgery in the 1990s, therefore, may require
      increasingly comprehensive rehabilitation services before returning to the
      community; however, information documenting functional progress during, and
      outcome after, a hospital-based rehabilitation program is scarce. METHODS: During
      a 14-month period, a consecutive sample of 44 patients who underwent cardiac
      surgery and were admitted to a rehabilitation unit in a tertiary acute hospital
      was studied. Thirty-one patients had coronary artery bypass graft, six had
      valvular surgery, and seven had both. Each patient's functional status on
      admission and discharge from the rehabilitation unit was assessed using the
      Functional Independence Measure. Other data studied included patient age and sex,
      premorbid medical problems, type of cardiac surgery, length of stay, and
      occurrence of medical complications in the acute and rehabilitation units.
      RESULTS: The mean Functional Independence Measure scores at rehabilitation unit
      admission and discharge were 76.1 +/- 17.1 and 96.7 +/- 19.4, respectively, and
      this difference was significant (P < 0.0001). The most significant correlates
      (alpha = 0.05) of the discharge Functional Independence Measure were admission
      Functional Independence Measure (P < 0.00001) and length of stay in the acute
      care unit (P = 0.0072). Age and presence of medical complications were not
      significant. CONCLUSION: Patients who undergo open heart surgery, many of whom
      have medical comorbidity, are able to demonstrate substantial functional
      improvement on an inpatient rehabilitation program before hospital discharge.

PMID- 8985799
TI  - National Survey on Gender Differences in Cardiac Rehabilitation Programs. Patient
      characteristics and enrollment patterns.
AB  - PURPOSE: Cardiac rehabilitation (CR) programs have been shown to promote numerous
      health benefits among patients with active coronary heart disease (CHD), but
      little is known about the percentage of eligible CHD patients who enroll in CR.
      METHODS: A survey was performed of 500 randomly chosen CR programs in operation
      in the United States during 1990. Patient characteristics and enrollment data
      were combined with data from the 1990 National Hospital Discharge Survey to
      estimate the percentage of eligible patients who participated in early outpatient
      (Phase II) CR programs after myocardial infarction (MI), after coronary
      angioplasty (PTCA), or after coronary artery bypass surgery (CABS). RESULTS:
      Completed surveys were returned by 163 programs (32.6%) with information on 1,322
      women and 1,418 men who enrolled in their programs in 1990. Women were older,
      more likely to be single, and had more traditional CHD risk factors than men.
      Only a minority of MI, PTCA, and CABS survivors enrolled in CR programs (10.8%,
      10.3% and 23.4%, respectively). Enrollment was particularly low for post-MI and
      post-CABS women as compared with men: 6.9% versus 13.3% (P < .001), and 20.2%
      versus 24.6% (P < .001), respectively. Enrollment was generally lowest for
      nonwhites, those over age 65, and those living in the southern United States.
      CONCLUSIONS: Cardiac rehabilitation programs are used by a minority of eligible
      patients, particularly among women, nonwhites, and the elderly. To meet newly
      released national guidelines that recommend CR services for most patients
      recovering from MI, PTCA, or CABS, and to still contain costs, new methods need
      to be explored that can expand the delivery of CR services in clinical settings.

PMID- 8985801
TI  - Guidelines development.

PMID- 8985802
TI  - Right and left atrial radiofrequency catheter therapy of paroxysmal atrial
      fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF), the most common arrhythmia, is due to
      multiple simultaneous wavelets of reentry in the atria. The only available
      curative treatment is surgical, using atriotomies to compartmentalize the atria.
      Therefore, we investigated a staged anatomical approach using radiofrequency
      catheter ablation lines to prevent paroxysmal AF. METHODS AND RESULTS: Forty-five
      patients with frequent symptomatic drug-refractory episodes of paroxysmal AF were
      studied. Progressively complex linear lesions were created by sequential
      applications of radiofrequency current in the right atrium and then in the left
      atrium if required. The outcome of the procedure was considered a success when
      the episodes of AF were either eliminated or recurred at a rate of no more than
      one episode (lasting < 6 hours) in 3 months. Patients who had no more than one
      episode per month were considered "improved." Right atrial ablation organized
      local electrical activity and led to stable sinus rhythm during the procedure in
      18 (40%) of the 45 patients. However, sustained AF remained inducible in 40 of 45
      patients, and the lesions failed to produce evidence of a significant linear
      conduction block/delay in all but four patients. There were no significant
      complications except for two transient sinus node dysfunctions. The procedure
      duration and fluoroscopic time were 248 +/- 79 and 53 +/- 22 min, respectively.
      Additional sessions were required in 19 patients to treat sustained right atrial
      flutter or arrhythmias linked to ectopic right or left atrial foci. During a mean
      follow-up of 11 +/- 4 months, right atrial ablation was successful in 15 (33%)
      patients, 6 without medication and 9 with a previously ineffective drug. Nine
      (20%) additional patients were improved. Ten patients with an unsuccessful
      outcome then underwent linear ablation in the left atrium. The procedure duration
      and fluoroscopy time were 292 +/- 94 and 66 +/- 24 min. A hemopericardium
      occurred in one patient. Two patients required reablation to treat ectopic atrial
      foci. Left atrial ablation terminated AF during the procedure in 8 patients, and
      sustained AF could not be induced in 5. Subsequent success was achieved in 6
      (60%) patients, including 4 without medication, and 1 additional patient was
      improved. CONCLUSIONS: Successful radiofrequency catheter ablation of drug
      refractory daily paroxysmal AF is feasible using linear atrial lesions
      complemented by focal ablation targeted at arrhythmogenic foci. Ablation only in
      the right atrium is a safe technique providing limited success, whereas linear
      lesions in the left atrium significantly increase the incidence of stable
      restoration of sinus rhythm, the inability to induce sustained AF, and the final
      success rate. The described technique is promising but must be considered
      preliminary because significant improvements are required to optimize lesion
      characteristics and shorten total procedure duration.

PMID- 8985803
TI  - Nonuniform anisotropy is responsible for age-related slowing of atrioventricular
      nodal reentrant tachycardia.
AB  - INTRODUCTION: AV nodal reentrant tachycardia cycle length has been shown to be
      longer in the elderly population. Microfibrosis associated with aging producing
      nonuniform anisotropic conduction or changes in membrane ionic properties could
      explain this finding. METHODS AND RESULTS: Forty-five patients (33 women and 12
      men) with typical AV nodal reentrant tachycardia were studied to analyze the
      effects of age on electrophysiologic characteristics of the tachycardia using
      high-density catheter mapping of the triangle of Koch. We classified patients
      into group A (age < or = 45 years, mean [+/-SD] 32.7 +/- 8.8, n = 27) and group B
      (age > 45 years, mean [+/-SD] 61.1 +/- 10.2, n = 18). Retrograde atrial
      activation was recorded during tachycardia by means of a 2-mm decapolar catheter
      at the His bundle, a quadripolar catheter at the high right atrium, a multipolar
      catheter (6 to 10 poles) in the coronary sinus, and a deflectable quadripolar
      catheter at the posterior triangle of Koch. The AH interval at the AV junction as
      well as HA intervals at several atrial sites were measured during tachycardia. HA
      intervals at all atrial recording sites except in the posterior triangle of Koch
      were significantly longer in group B, as well as the tachycardia cycle length
      (362 vs 329 msec, P = 0.01). The mean AH interval was prolonged by 24 msec in
      group B, but this difference did not reach statistical significance. A sequential
      pattern of retrograde atrial activation during tachycardia was more frequently
      recorded in group B. CONCLUSIONS: Since the delayed activation to the atrium was
      heterogeneous, transverse nonuniform anisotropic conduction is a likely
      explanation of these age-related modifications of AV nodal reentrant tachycardia
      characteristics.

PMID- 8985804
TI  - Response to beta blockers in patients with neurocardiogenic syncope: how to
      predict beneficial effects.
AB  - No definitive data are available about the possibility of predicting improvement
      in patients with neurocardiogenic syncope treated with beta blockers. Among 112
      patients with syncope and a positive head-up tilt test (HUT), independent
      predictors for prevention of symptoms with beta blockers were determined using
      the Cox proportional hazards model. Each patient underwent HUT at 70 degrees for
      20 minutes both in the drug-free state and during isoproterenol infusion given to
      increase the heart rate by at least 25%. Fifty-nine patients had a positive HUT
      during isoproterenol infusion and 53 in the drug-free state. All patients were
      then given esmolol infusion at 500 micrograms/kg per minute for 3 minutes
      followed by 300 micrograms/kg per minute maintenance dose. HUT was then repeated
      as previously described with or without isoproterenol, depending upon the initial
      positive response. Regardless of the response during esmolol, all patients were
      treated with metoprolol 50 to 100 mg twice daily. At follow-up, 36 patients
      experienced symptom relapse. Four of them had negative HUT on esmolol, whereas
      the remaining 32 did not respond to the acute infusion of esmolol. Only four
      patients with positive HUT on esmolol had a favorable response to metoprolol.
      Patients responding to metoprolol were older (55 +/- 12 years vs 42 +/- 15 years,
      P < 0.05). Response to metoprolol was predicted by a negative test on esmolol (P
      < 0.0001) and a positive HUT on isoproterenol (P < 0.001). Age older than 42
      years was also associated with a higher likelihood of metoprolol success (P <
      0.02). CONCLUSION: Acute challenge with esmolol infusion appears to be an
      accurate predictor of response to chronic beta blockers, together with age and a
      positive HUT during low-dose isoproterenol infusion.

PMID- 8985805
TI  - Effect of coronary perfusion of heptanol on conduction and ventricular
      arrhythmias in infarcted canine myocardium.
AB  - INTRODUCTION: Abnormal cellular coupling is a major constituent of the slow,
      dissociated conduction that supports ventricular tachycardia (VT) following
      myocardial infarction. Agents that modulate cellular coupling may exert either
      proarrhythmic or antiarrhythmic effects. METHODS AND RESULTS: The effects of
      modulating cellular coupling on conduction and susceptibility to inducible VT
      were studied in 11 dogs with healed left anterior descending (LAD) infarction.
      The LAD circulation was isolated and supplied with arterial blood via a constant
      flow bypass system. Localized intracoronary infusion of heptanol, an agent with
      relatively specific effects on intracellular coupling, was performed using this
      bypass system. Heptanol produced dose-dependent changes in cardiac conduction,
      assessed by delayed local activation times in sinus rhythm (0.5 mM: 11.9% +/-
      11.0% change, P = 0.005; 1.0 mM: 45.8% +/- 25.5% change, P = 0.0004) and slowed
      conduction velocity both transverse and longitudinal to fiber orientation.
      Sustained VT was not induced in any of the control animals. During infusion of
      0.5 mM heptanol, uniform sustained VT was inducible in 4 of 11 animals (P =
      0.027). During infusion of 1.0 mM heptanol, sustained VT was induced in only 1 of
      9 animals. CONCLUSIONS: In the canine model of healed myocardial infarction,
      heptanol had a bimodal effect on susceptibility to inducible VT. Low-dose
      heptanol facilitated the induction of sustained VT, and high-dose heptanol had an
      antiarrhythmic effect. This suggests that agents that modulate coupling may
      significantly modify susceptibility to VT following myocardial infarction.

PMID- 8985806
TI  - Flecainide and the electrophysiologic matrix: the effects of flecainide acetate
      on the determinants of cardiac excitability in sheep Purkinje fibers.
AB  - Flecainide was associated with excess mortality distributed virtually equally
      throughout the period of the Cardiac Arrhythmia Suppression Trial, suggesting the
      intersection of two events, drug effect and perhaps ischemia. Flecainide's effect
      on active properties has been studied extensively, but nothing is known of its
      effects on passive properties or on the balance among active and passive cellular
      properties that determines cardiac excitability. The multiple microelectrode
      method of intracellular current application and transmembrane voltage recording
      was used in sheep Purkinje fibers to determines strength- and charge-duration as
      well as constant current-voltage relationships and to estimate active properties,
      liminal length, and cable properties at a normal [K+]o and in a setting of
      hyperkalemia analogous to that of ischemia. A computer tracked in time the
      alterations in the active and passive properties relevant to excitability.
      Flecainide slightly decreased excitability at a normal [K+]o, primarily by
      depressing the sodium system with some contributory effect of passive properties.
      At high [K+]o, flecainide caused a frequency-dependent decrease in excitability
      and conduction, the latter best interpreted as a failure of the fiber to attain
      the liminal length requirements to produce a local action potential due primarily
      to an effect on sodium conductance. Together, the observations suggest that the
      action potential is the local phenomenon and that the propagated event is the
      sequential fulfillment of liminal length requirements. The data were interpreted
      in terms of the electrophysiologic matrix first proposed in detail in this
      Journal, which indicated that the electrophysiologic universe moved as a system
      in response to the drug and a change in [K+]o, the presumed antiarrhythmic and
      proarrhythmic electrophysiologic matrices for flecainide were quite similar, and
      the matrical configuration shared characteristics with the matrices of other
      drugs with known proarrhythmic potential.

PMID- 8985807
TI  - Modeling the interaction between propagating cardiac waves and monophasic and
      biphasic field stimuli: the importance of the induced spatial excitatory
      response.
AB  - INTRODUCTION: Biphasic (BP) defibrillation waveforms have been shown to be
      significantly more efficacious than equivalent monophasic (MP) waveforms.
      However, when defibrillation fails, it tends to do so first in distal regions of
      the heart where induced field gradient magnitudes are lowest. We tested the
      hypothesis that the improved efficacy of BP waveforms results from their enhanced
      ability to prevent the initiation of new postshock activation fronts behind
      preexisting wavetails, rather than from any significantly improved ability to
      terminate preexisting wavefronts. METHODS AND RESULTS: An idealized computer
      model of a one-dimensional cardiac strand was used to investigate the spatial and
      temporal interactions between an underlying propagation front (or tail) and
      uniform MP or BP field stimuli of various intensities. Axial discontinuities from
      intercellular junctions induced sawtooth patterns of polarization during such
      field stimuli, enabling the shocks to interact directly with all cells. MP and BP
      diastolic thresholds were essentially equal. All suprathreshold MP and BP field
      stimuli successfully terminated preexisting wavefronts by directly depolarizing
      tissue ahead of those fronts, thus blocking their continued progression. However,
      the postshock response at the wavetail was significantly dependent on the shape
      and strength of the administered field. Low-strength MP stimuli induced an all-or
      none excitation response across the wavetail, producing a sharp spatial
      transmembrane voltage gradient from which a new sustained anterogradely
      propagating wavefront was initiated. In contrast, low-strength BP field stimuli
      induced a spatially graded excitatory response whose voltage gradient was
      insufficient to initiate such a wavefront. Higher-strength MP and BP stimuli both
      produced graded excitatory responses with no subsequent propagation. CONCLUSIONS:
      Shock-induced spatial "all-or-none" excitatory responses facilitate, and graded
      excitatory responses prevent, the postshock initiation of new propagating
      wavefronts. Moreover, BP field stimuli can induce such graded excitatory
      responses at significantly lower stimulus strengths than otherwise equivalent MP
      stimuli. Therefore, these results support an alternative "graded excitatory
      response" mechanism for the improved efficacy of BP over MP field stimuli in low
      gradient regions.

PMID- 8985808
TI  - Alteration of human placental vascular tone by antiarrhythmic medications in
      vitro.
AB  - INTRODUCTION: Antiarrhythmic medications are commonly used during pregnancy for
      treatment of maternal or fetal arrhythmias, but little is known about their
      effect on human placental vascular tone and, consequently, placental blood flow.
      The objective of this study was to evaluate the tone responses caused by
      antiarrhythmic medications in human placental vessels from normal term
      pregnancies in vitro. METHODS AND RESULTS: Isolated human placental arteries and
      veins from uncomplicated term pregnancies incubated in Krebs'-bicarbonate under
      5% oxygen/5% carbon dioxide/balance nitrogen (PO2 35 to 38 torr) were exposed to
      cumulative doses of quinidine, procainamide, lidocaine, flecainide, propranolol,
      amiodarone, verapamil, digoxin, and adenosine after submaximal contraction with 5
      hydroxytryptamine. The study was conducted both in the presence and absence of
      endothelium. The addition of the tested medications caused a significant, dose
      dependent relaxation of human placental arteries and veins except for adenosine,
      which induced a sustained, dose-dependent contraction of human placental vessels
      regardless of the presence or absence of tone. Removal of the endothelium did not
      alter these responses. CONCLUSIONS: Based on these results, the medications
      tested should have no decremental effect on placental blood flow, with the
      possible exception of adenosine, which causes significant, dose-dependent
      contraction of human placental vessels in vitro. Should similar contraction be
      present in vivo, it may have an adverse effect on the fetus when administering
      adenosine to pregnant women at term or during labor.

PMID- 8985809
TI  - Electrophysiologic study and radiofrequency ablation in patients with
      intracardiac tumors and accessory pathways: is the tumor the pathway?
AB  - INTRODUCTION: There is a strong association of cardiac rhabdomyomas with the
      Wolff-Parkinson-White syndrome. This report describes the results of
      investigations in two patients with accessory pathway-mediated AV reciprocating
      tachycardia coexisting with intracardiac tumors. METHODS AND RESULTS: Two
      patients with intracardiac tumors had mapping of the accessory pathway.
      Echocardiograms obtained in the electrophysiology laboratory while the ablation
      catheter was at the site of successful radiofrequency ablation demonstrated a
      close correspondence between the site of intracardiac tumor and the location of
      the accessory pathway. CONCLUSIONS: These results lend support to the hypothesis
      that accessory pathways in patients with intracardiac tumors, such as
      rhabdomyomas, are not typical Kent bundles, but instead are either part of the
      intracardiac tumor or are closely related to the tumor. Ablation is possible in
      at least some patients with accessory pathways associated with intracardiac
      tumors.

PMID- 8985810
TI  - Radiofrequency catheter ablation of idiopathic ventricular tachycardia
      originating in the anterior fascicle of the left bundle branch.
AB  - INTRODUCTION: Idiopathic ventricular tachycardia (VT) originating in or close to
      the anterior fascicle of the left bundle is rare. A patient with no structural
      heart disease and VT with a right bundle branch block configuration and right
      axis deviation underwent an electrophysiologic examination. METHODS AND RESULTS:
      Both endocardial activation mapping during VT and pacemapping were performed via
      a transseptal approach to localize the site of origin of the VT. Endocardial
      recordings of the His bundle and the posterior and anterior fascicles of the left
      bundle branch revealed an origin of the VT in or close to the anterior fascicle.
      The Purkinje potential at that site preceded the QRS complex by 20 msec, with
      pacemapping showing an optimal match between the paced rhythm and the clinical
      VT. RF energy delivered at this site terminated the VT. A left anterior hemiblock
      appeared after RF ablation. Ten months later, the patient is free from
      recurrences of VT. CONCLUSIONS: Idiopathic VT originating in or close to the
      anterior fascicle was cured by RF ablation. A Purkinje potential preceding the
      QRS during tachycardia and an optimal pacemap were used to guide RF ablation.

PMID- 8985811
TI  - Is the automatic atrial defibrillator a promising approach?
AB  - Atrial fibrillation is a common arrhythmia, accounting for more consumption of
      medical resources than any other arrhythmia. The impact of the disease results
      from the combination of a loss of atrial contraction, and atrial control over
      cardiac rate. Studies in animals demonstrated the basic feasibility of atrial
      defibrillation using electrodes passed intravenously. Subsequent studies in
      patients confirmed that low-energy shocks were effective in converting atrial
      fibrillation and were safe if delivered synchronous to the R wave in the absence
      of a short preceding RR interval. Preliminary experience suggests that a small
      implanted device might provide beneficial therapy for patients with recurring
      episodes of persistent, drug-refractory, atrial fibrillation.

PMID- 8985812
TI  - Radiofrequency catheter ablation of common atrial flutter in 200 patients.
AB  - INTRODUCTION: The purpose of this study was to evaluate the efficacy and safety
      of radiofrequency (RF) catheter ablation of common atrial flutter and to
      determine the optimum target sites in a large series of patients. Three different
      approaches were used to target the ablation site. The first used a combined
      anatomic and electrophysiologic approach, whereas the second and the third
      approaches relied primarily on anatomic guidelines to target the critical area in
      the atrial flutter reentrant circuit located in the low right atrium. BACKGROUND:
      Recent studies report the efficacy of RF current application in the low right
      atrial region to interrupt and prevent recurrences of common atrial flutter using
      either anatomic or electrophysiologic targets. However, larger groups of patients
      are required to confirm the efficacy of this technique and to specify the target
      sites. METHODS AND RESULTS: Two hundred consecutive patients with drug-resistant
      common atrial flutter were studied. In the first 50 patients, target sites were
      localized using both anatomic landmarks and electrophysiologic parameters. The
      anatomic landmarks were area 1 between the tricuspid valve and inferior vena cava
      orifice; area 2 between the tricuspid valve and coronary sinus ostium; and area 3
      between the inferior vena and coronary sinus. The electrophysiologic criterion
      was to ablate when there was an atrial electrogram occurring during the plateau
      phase (preceding F wave). The first targeted area was that giving the more stable
      catheter position. In the following 30 patients, we assessed the effect of RF
      energy application in a single line to area 1 in the first 10 patients, area 2 in
      the next 10, and area 3 in the last 10 patients. In the last 120 patients, RF
      energy was applied only in area 1 using repeated applications. RF energy of 12 to
      30 W, or that achieving a temperature of 70 degrees C, was applied for 60 to 90
      seconds at each site. The endpoint of the ablation procedure was interruption and
      noninducibility of common atrial flutter in the first 110 patients and additional
      isthmal block in 48 of the last 90 patients. Overall, atrial flutter was
      interrupted and rendered noninducible after a single session in 191 (95%)
      patients and could not be interrupted in 9 (4.5%) patients. The mean number of RF
      applications was 12 +/- 8. After a mean follow-up of 24 +/- 9 months, recurrences
      occurred in 31 (15.5%) patients, 26 of whom underwent a successful second or
      third session without further recurrences of atrial flutter. Atrial fibrillation
      not documented before the ablation was detected in 11 patients. On a
      retrospective analysis of the final successful site in the first group of 50
      patients, the location was in area 1 in 39% of patients; area 2 in 36% of
      patients, and area 3 in 25% of patients. Atrial electrograms recorded at these
      sites showed a single spike pattern in 46% of patients, and double spike pattern
      (28%) or fractioned electrogram in 26% patients. When lines of RF lesions were
      placed at several sites, they produced a success rate of 70%, 40%, and 10% at
      areas 1, 2, and 3 respectively. In the last series of 120 patients, the procedure
      was successful in 119 patients: 92% of whom were successfully treated only by a
      linear lesion between the tricuspid annulus isthmus and the inferior vena cava,
      and the other 8% by additional applications near the coronary sinus ostium. No
      complications were observed. CONCLUSIONS: RF catheter ablation of atrial flutter
      can be done with a high success rate and is safe. The highest success rate is
      achieved with RF energy applied in the isthmus between the inferior vena cava
      orifice and the tricuspid valve. However, 15.5% of patients need multiple
      sessions to achieve success because of recurrence of flutter. Further follow-up
      is needed to evaluate the long-term effects of this procedure.

PMID- 8985813
TI  - Variable PR intervals: what is the rhythm?

PMID- 8985814
TI  - Cigarette smoking, abdominal blood flow and abdominal diseases.

PMID- 8985815
TI  - Doppler ultrasound evaluation of acute effects of cigarette smoking on portal
      blood flow in man.
AB  - The acute systemic haemodynamic effects of cigarette smoking are well known, but
      there are no studies dealing with the possible smoke-related acute changes of
      splanchnic circulation in man. In the present study we evaluated the acute
      effects of cigarette smoking on portal blood flow (PBF) in normal subjects by the
      use of Doppler ultrasound. Twenty-three normal volunteers were asked to smoke two
      cigarettes with a known total nicotine content (1.1 mg each) in a supine
      position. Each cigarette was smoked during a 5 min period and a 5 min interval
      between the two cigarettes was allowed. Both mean PBF velocity and volume were
      evaluated at time 0 (basal values) and 8, 15, 30, 45 and 60 min after the first
      inhalation of the first cigarette. The basal mean PBF velocity (22 cm/s; 95% CI
      20.9-24.2) was significantly decreased at 8 min (19 cm/s; 95% CI 17.9-20.8; P <
      0.0007) and 15 min (20 cm/s; 95% CI 17.8-21.3; P < 0.005). Similarly, the PBF
      volumes at 8 min (710 mL/min; 95% CI 660-876; P < 0.002) and 15 min (750 mL/min;
      95% CI 650-862; P < 0.005) were significantly lower than those measured at time 0
      (850 mL/min; 95% CI 766-987). Both mean PBF velocity and volume measured at
      successive times did not differ significantly from basal values. The present
      study shows that cigarette smoking causes acute and transient reduction of PBF
      velocity and volume in normal subjects.

PMID- 8985816
TI  - Hepatitis C transmission between spouses.
AB  - To examine inter-spouse transmission as one of the potential routes of infection
      for hepatitis C virus (HCV), 121 patients with HCV-related chronic liver disease
      who tested positive for antibodies to HCV (anti-HCV) and their spouses were
      studied. Of these, 21 (17.4%) patients had spouses with anti-HCV. In 12 couples,
      the HCV genotype matched (type II: 10 couples, type III: two couples). The
      genotype differed in six couples. One patient was positive for anti-HCV, but
      negative for HCV-RNA, while the spouse was positive for both. The remaining two
      couples were only positive for anti-HCV. Genetic heterogeneity in the
      hypervariable region 1 of HCV was analysed in 11 couples with matched genotypes.
      In two couples, no mutation was recognized in the putative E2/NS1 genes using the
      heteroduplex method. The present study provides evidence to verify household
      transmission of HCV between patients and their spouses. These results suggest
      that inter-spouse transmission may be a potential route of transmission of HCV
      infection. However, other environmental factors (e.g. the duration of the
      marriage) cannot be ignored.

PMID- 8985817
TI  - Effects of combination therapy with interferon and ofloxacin on chronic type C
      hepatitis: a pilot study.
AB  - Interferon is effective in only a limited number of patients with the 1b type of
      hepatitis C virus (HCV), indicating that a combination therapy with other
      antiviral drugs may be essential to obtain better results. In the present pilot
      study, the effects of a combination therapy with interferon (IFN) and an
      antibacterial drug, ofloxacin, were analysed. Ten patients with chronic type C
      hepatitis received the combination therapy (combination group). Six million units
      of natural IFN-alpha were administered daily for 3 weeks and then three times a
      week for 21 weeks. The combination therapy was initiated at the beginning of the
      eighth week of IFN treatment and 600 mg ofloxacin per day was administered for 12
      weeks. As a control, changes in HCV-RNA were also analysed in patients who were
      treated with only IFN for the same period (IFN-alone group). In the combination
      group, serum transaminase levels and the titres of HCV decreased significantly
      with ofloxacin administration. Such changes were not observed in the IFN-alone
      group. The incidence of HCV-negativity at the end of ofloxacin administration of
      the combination group was significantly higher than in the IFN-alone group. The
      complete response rate was twice as high in the combination group as in the IFN
      alone group. In two patients who did not respond well to the IFN-alone treatment,
      ofloxacin administration was commenced after the 24th week. Serum transaminase
      levels were normalized and HCV-RNA became negative in these two patients after
      the administration of ofloxacin. These results suggest that combination therapy
      with IFN and ofloxacin may be an effective treatment for chronic type C
      hepatitis.

PMID- 8985818
TI  - Case report: agranulocytosis induced by interferon-alpha therapy for chronic
      hepatitis C.
AB  - A 60-year-old woman presented with chronic active hepatitis C whose HCV-RNA
      genotype was II according to Okamoto's classification and serum HCV-RNA
      concentration was 10(4) copies/mL. Agranulocytosis was induced 13 days from the
      commencement of interferon (IFN)-alpha 2b (6 MU/day) therapy, so the IFN therapy
      was immediately discontinued. The agranulocytosis improved rapidly with the
      administration of a granulocyte colony stimulating factor (G-CSF). The
      possibility that IFN was associated with maturational arrest of myeloid
      progenitor cells was considered. During the course of 3 years of follow-up, her
      liver function has remained normal and serum HCV-RNA remains negative.

PMID- 8985819
TI  - Aminoterminal propeptide of type III procollagen and hyaluronan in patients with
      primary biliary cirrhosis: markers of fibrosis in primary biliary cirrhosis.
AB  - The aminoterminal propeptide of type III procollagen (PIIINP) and hyaluronan have
      previously been studied in different liver diseases. The results of these studies
      are controversial. The aim of the present study was to examine the relationship
      between PIIINP and hyaluronan levels and the clinical, biochemical and
      histological features of primary biliary cirrhosis (PBC) and its prognosis. Fifty
      five PBC patients were studied at the time of diagnosis of PBC and were followed
      up for a mean of 58 months. During the follow-up period 21 patients died. In
      addition, 30 healthy subjects were examined in the present study. Hyaluronan and
      PIIINP were measured by radioimmunoassay and the levels of both PIIINP and
      hyaluronan were higher in PBC patients than in healthy volunteers (P < 1.8 x 10(
      6) and 1.6 x 10(-9), respectively). Hyaluronan and PIIINP levels were above
      normal values in 82 and 84% of PBC patients, respectively. There were
      correlations between PIIINP and hyaluronan and the histological stage of PBC (r =
      0.44, P < 0.004 and r = 0.56, P < 0.00001, respectively). The correlation between
      PIIINP and hyaluronan was 0.46 (P < 0.0035). In symptomatic patients, both PIIINP
      and hyaluronan values were higher than in controls (P < 0.002 and P < 0.006,
      respectively). The levels of PIIINP correlated significantly with bilirubin (r =
      0.43, P < 0.006), while hyaluronan was correlated with age (r = 0.33, P < 0.015),
      pruritus (r = 0.32, P < 0.02), fatigue (r = 0.41, P < 0.003), hepatomegaly (r = 
      0.46, P < 0.0008), the presence of oesophageal varices (r = 0.34, P < 0.002),
      weight loss (r = 0.29, P < 0.05), bilirubin (r = 0.54, P < 0.0001), albumin (r = 
      0.30, P < 0.04), extent of fat excretion (r = 0.53, P < 0.009) and length of
      symptomatic period before diagnosis of PBC (r = 0.43, P < 0.002). Using Cox's
      logistic regression analysis, survival was found to be influenced by bilirubin
      concentration but not by hyaluronan, PIIINP, age, albumin or histological stage.
      Therefore, hyaluronan is a more sensitive marker for predicting advanced PBC than
      is PIIINP. However, neither hyaluronan nor PIIINP gave any indication of
      prognostic outcome.

PMID- 8985820
TI  - Case report: acanthosis nigricans in association with primary biliary cirrhosis:
      resolution after liver transplantation.
AB  - A case is described of a 58 year old Caucasian male with primary biliary
      cirrhosis (PBC) who first presented with acanthosis nigricans of both axillae,
      skin pigmentation, which was pronounced over the posterior surface of the neck,
      and generalized pruritus. Following orthotopic liver transplantation for
      progressive liver disease, the skin pigmentation, pruritus and acanthosis
      nigricans resolved. It is believed that this is the first reported case of
      acanthosis nigricans occurring in association with PBC, a phenomenon that
      resolved after liver transplantation.

PMID- 8985821
TI  - Contributions of the Brisbane Liver Group to knowledge of iron metabolism.

PMID- 8985822
TI  - Cellular iron processing.
AB  - Iron is transported in the blood plasma, mainly bound to transferrin, but in
      abnormal conditions other iron containing compounds may become important. These
      include ferritin, haemopexin-haem, haptoglobin-haemoglobin and non-specific non
      transferrin-bound iron, all of which are taken up from the circulation by the
      liver. Transferrin-bound iron can be used by all types of cells in amounts that
      depend on their complement of transferrin receptors. Immature erythroid cells are
      the most active in this function. Investigations using reticulocytes as an
      example of erythroid cells have demonstrated the presence of two mechanisms for
      the uptake of ferrous iron. One, a high affinity process disappears as
      reticulocytes mature. It probably represents the mechanism by which iron derived
      from transferrin is transported into the cytosol after receptor-mediated
      endocytosis of the iron-transferrin complex. The other mechanism has a lower
      affinity for iron, is retained when reticulocytes mature and is probably
      associated with Na+ transport across the cell membrane. The physiological
      characteristics of the two iron transport processes and the evidence for the
      above conclusions are summarized in the present paper.

PMID- 8985823
TI  - Control of iron absorption.
AB  - Intestinal iron absorption plays an essential role in body iron homeostasis,
      although the mechanism by which iron moves across the cells of the intestinal
      epithelium and the way in which this process is regulated are poorly understood.
      Signals to alter iron absorption are received from the body by cells of the
      intestinal crypt and these signals are translated into an absorption response
      after the cells have migrated up the villus and differentiated into mature
      absorptive enterocytes. The intracellular iron concentration of the crypt cell
      may play an important role in the regulation of this process. Biochemical
      investigations on the mechanism of iron absorption have met with only limited
      success and a molecular understanding of this mechanism appears most likely to
      come from the identification of the genes affected in various inherited
      disturbances of iron absorption in several mammalian species.

PMID- 8985824
TI  - Serum ferritin: does it differ from tissue ferritin?
AB  - Serum ferritin isolated from the horse was structurally compared with horse
      spleen ferritin and was found to differ markedly in molecular weight, iron
      content, carbohydrate, subunit size and amino acid sequence. The results are
      summarized and initial results obtained with candidate clones of pieces of two
      serum ferritin subunits are described.

PMID- 8985825
TI  - Iron in an Australian population: too little or too much?

PMID- 8985826
TI  - Alcohol and iron: one glass of red or more?
AB  - The consumption of excessive amounts of alcohol affects human iron homeostasis
      and an association of iron overload and heavy alcohol consumption has been
      recognized for many years. Both major proteins of iron metabolism, ferritin and
      transferrin, are affected by alcohol. Increased hepatic iron levels are seen in a
      high proportion of alcoholic subjects, sometimes causing confusion in diagnosis
      between alcoholic liver disease and iron-overload disease. The pattern of
      deposition of this iron in alcoholics, however, differs from that seen in the
      iron-overload disease haemochromatosis. Excessive alcohol consumption causes
      transferrin to become carbohydrate deficient, which allows it to be used as an
      efficient biochemical marker of alcohol abuse. It is concluded that alcohol
      consumption in moderation is unlikely to have deleterious health consequences.

PMID- 8985827
TI  - Current status in identifying the haemochromatosis gene.

PMID- 8985828
TI  - Determinants of disease expression in Australian haemochromatosis patients.
AB  - Many of the clinical manifestations of haemochromatosis are determined by the
      hepatic iron concentration which, in turn, may be influenced by environmental and
      genetic factors. The environmental factors that influence iron stores include
      age, gender and blood loss (pathological and physiological). There is evidence
      that genetic factors also influence hepatic iron accumulation, as patients with
      two copies of the ancestral haplotype accumulate more iron than subjects with one
      or no copies of the ancestral haplotype. Concordance of iron storage between
      siblings also suggests genetic factors play an important role in determining
      disease expression. However, clarification of the exact role of genetic factors
      awaits the conduct of further studies following the cloning of the
      haemochromatosis gene.

PMID- 8985829
TI  - Review: molecular pathogenesis of hepatic acute porphyrias.
AB  - The molecular cloning of cDNA and genes encoding enzymes of the haem biosynthetic
      pathway have permitted the genetic defects underlying acute intermittent
      porphyria (AIP) and hereditary coproporphyria to be unravelled. In AIP, many
      different gene abnormalities have been documented since 1989. The prevalence of
      specific defective alleles among AIP families depends on which human population
      is studied. Founder effects are likely to account for a high frequency of a
      single mutation in Finland and, to a lesser extent, in Holland, while many other
      mutations have only been found once, each of them in a single family. In
      hereditary coproporphyria several different mutations have already been
      identified since 1994, suggesting that a large allelic heterogeneity also exists.
      The search for mutations in variegate porphyria has just started since the recent
      publication of the human cDNA sequence. Direct detection of the mutations using
      DNA analysis brings a growing contribution to the detection of asymptomatic
      carriers among relatives of porphyric patients and will, therefore, improve the
      prevention of acute attacks.

PMID- 8985831
TI  - Morgagni: his book, vision and views on hepatic coma.
AB  - The study of pathological anatomy reached a culmination in the magnum opus of
      Morgagni, The Seats and Causes of Diseases. It represented an innovative way of
      looking at the patient and his illness, a change that Foucault described as
      occurring in the 18th century. Physicians saw symptoms penetrating the body and
      converging upon an organ. We suggest that Morgagni and his fellow workers derived
      their vision from the practice of visual perspective discovered by Italian
      Renaissance artists. Perceiving in three dimensional terms, Morgagni added
      spatial depth to our understanding of disease. His acute vision was brilliantly
      displayed in his views of hepatic coma. He was among the first to provide the
      clinical-pathological associations of acute liver failure. The limitations of
      gross morphology precluded a complete elucidation of the disorder.

PMID- 8985830
TI  - Construction of retroviral vectors to induce strong hepatoma cell-specific
      expression of cytokine genes.
AB  - Continuing advances in molecular biology have provided tools for a promising
      approach to the treatment of cancer. Among the various strategies of gene therapy
      for cancer, many are aimed at killing tumour cells indirectly by the induction or
      reinforcement of a host immune response by gene transduction of various
      cytokines, major histocompatibility complex or immune accessory molecules. In the
      present study, we selected the tumour necrosis factor-alpha, interleukin-2 and
      interleukin-3 genes as potential cytokine genes to induce antitumour effects. We
      constructed retroviral vectors carrying these cytokine genes under the control of
      the murine albumin enhancer and promoter and retrovirally transduced these genes
      into hepatoma and non-hepatoma cell lines. Strong expression of the cytokine
      genes was induced in transduced hepatoma cells, while no evident expression was
      detected in transduced non-hepatoma cells. These results demonstrate the hepatoma
      specific expression of cytokine genes and imply the feasibility of in vivo gene
      transfer into hepatomas without affecting any other tissues. Furthermore, these
      cytokine genes were expressed much more intensively when they were derived from
      the albumin enhancer and promoter than when derived from the simian virus 40
      early region promoter. These results indicate that transcriptional regulatory
      sequences specific for the target tissues could be preferable to viral promoters
      for the gene therapy of cancer.

PMID- 8985833
TI  - Effect of the microtubular inhibitor vinblastine on ferritin clearance and
      release in the rat.
AB  - We have previously demonstrated that colchicine inhibits ferritin clearance from
      the circulation of normal and iron-loaded rats and stimulates endogenous ferritin
      release into both the serum and bile of iron-loaded rats. The aim of the present
      study was to determine the effect of vinblastine on ferritin clearance and
      release in normal and iron-loaded rats. Vinblastine was administered at either 1
      or 10 mg/kg to both normal and iron-loaded rats, infused over a 5 h period with
      either a rat liver ferritin or saline solution. Serum and biliary ferritin levels
      were determined every 30 min. After 5 h, 90% of the infused ferritin was cleared
      from the circulation in the absence of vinblastine. Low-dose vinblastine
      decreased ferritin uptake 10-20% in iron-loaded rats. High-dose vinblastine
      inhibited ferritin clearance by 25% in normal rats and 20-40% in iron-loaded
      rats. Vinblastine administration caused a 2-3-fold increase in the serum ferritin
      concentration and a 3-5-fold peak in biliary ferritin levels. Thus, vinblastine
      caused the release of endogenous ferritin into both the serum and bile of iron
      loaded rats in the presence of a ferritin load. We therefore conclude that
      disturbed microtubule function accounts for the observed inhibition of ferritin
      uptake and intracellular transport; however, the mechanism of increased ferritin
      release remains unclear.

PMID- 8985832
TI  - ATP modulates sulfobromophthalein uptake in rat liver plasma membrane vesicles.
AB  - The hepatic uptake of the bilirubin-bilirubin-sulfobromophthalein (BSP) group of
      organic anions is a carrier-mediated process and is accounted for by at least
      four distinct plasma membrane proteins (bilitranslocase, BSP/bilirubin-binding
      protein, organic anion-binding protein and the organic anion transport protein).
      In order to investigate the regulation of basolateral organic anion uptake, BSP
      transport was measured in rat basolateral liver plasma membrane vesicles in the
      presence of ATP. ATP significantly stimulated the electroneutral uptake of BSP
      with an increment in Vmax compared with control (1.57 +/- 0.14 vs 0.73 +/- 0.06
      nmol BSP/mg protein per 15 s, respectively; P < 0.001) while the apparent K(m)
      was not changed significantly (12 +/- 1 vs 12 +/- 2 mumol/L). The stimulatory
      effect was dose-dependent for ATP (K(m) 1.01 +/- 0.37 mmol/L). ATP had no
      detectable effect on the electrogenic component of BSP transport. Other
      nucleotides (ADP, AMP, GTP) and non-hydrolysable ATP did not enhance BSP uptake,
      suggesting that ATP hydrolysis was necessary for the effect. This was supported
      by the lack of effect on BSP uptake when ATP was added in the presence of
      vanadate. The addition of phorbol-12-myristate 13-acetate, an activator of
      protein kinase C (PKC), increased BSP uptake in a dose-dependent manner in the
      presence, but not in the absence, of ATP. Incubation of vesicles with
      staurosporine, an inhibitor of PKC activity, resulted in a dose-dependent
      inhibition of ATP-sensitive BSP transport. These data indicate that
      electroneutral BSP hepatic uptake is modulated by ATP. The effect is related to
      ATP hydrolysis and involves the activity of PKC.

PMID- 8985834
TI  - Studies on the hypomethylation of c-myc, c-Ha-ras oncogenes and histopathological
      changes in human gastric carcinoma.
AB  - In order to study the status of DNA methylation of specific oncogenes and the
      relationship between them and the pathological changes in gastric carcinoma, we
      analysed the methylated status of c-myc, c-Ha-ras oncogenes by Southern blot
      hybridization. Genomic DNA from cancerous, paracancerous and non-cancerous areas
      of surgically resected specimens were examined in 22 cases of advanced human
      gastric carcinoma. Specimens were digested by the restriction endonucleases
      MspI/HpaII, which are able to cleave between methylated and non-methylated
      cytosine at their nucleotide recognition site the DNA 5'-CCGG sequence, and were
      hybridized with c-myc, c-Ha-ras oncogene probes. Moreover, the corresponding
      pathological changes in gastric carcinoma were observed. The results showed that
      c-myc, c-Ha-ras oncogenes from cancerous (10/22, 5/10) and paracancerous areas
      (13/22, 4/10) were hypomethylated and that there was no significant relationship
      between them and the histopathological changes.

PMID- 8985835
TI  - Clinicopathological significance of intestinal and diffuse types of gastric
      carcinoma in Taiwan Chinese.
AB  - The present study sought to evaluate the clinicopathological features of our
      gastric cancer patients in terms of a modified Lauren's histological
      classification and compared the results with those from studies from Japan and
      Western countries. A total of 536 consecutive patients with gastric cancer were
      treated surgically between December 1987 and December 1993. A clinicopathological
      analysis was only performed for intestinal types (IT) and diffuse types (DT) of
      gastric cancer because patients falling into the 'other' category were too small
      to produce meaningful data. Of 536 cases of gastric cancer, 268 (50%) were IT,
      231 (43.1%) were DT and 37 (6.9%) were of the other type. The overall IT:DT ratio
      was 1.2. Gastric cancer patients with IT (in contrast to DT) were characterized
      by older age, male dominance, smaller tumours, the tumour often being located in
      the lower and upper third of the stomach and less peritoneal metastasis. In both
      sexes, the peak incidence of gastric cancer patients was in the age group 65-74
      years. Men had higher proportions of IT carcinoma than women. The IT:DT ratio for
      men and women was 1.4 and 0.4, respectively. Although the increased ratio of
      IT:DT paralleled the advance of age in both sexes, the transitional age (the age
      at which the IT:DT ratio exceeds 1.0) in male patients (age group 51-64 years)
      was earlier than for female patients (age group 65-74 years). Patients with IT
      gastric cancer had a significantly better survival rate than those with DT.
      However, the type of carcinoma (IT or DT) was not an independent predictor of
      survival. These data indicate that gastric cancer in Taiwan Chinese has different
      biological behaviour in terms of IT and DT. The clinicopathological features in
      IT and DT carcinoma are similar to studies from Japan and from Western countries.

PMID- 8985836
TI  - Keratinocyte growth factor is an endogenous stimulant of rabbit gastric
      epithelial cell proliferation and migration in primary culture.
AB  - Mesenchymal-epithelial interactions are important in the gastric mucosal repair.
      However, specific factors responsible for such interactions have not been
      established. In the present study, keratinocyte growth factor (KGF) significantly
      stimulated proliferation of gastric epithelial cells dose dependently and
      synergistically with hepatocyte growth factor (HGF), epidermal growth factor
      (EGF) and insulin. Restitution of gastric epithelial monolayers was also
      assessed, using a round wound restitution model. Keratinocyte growth factor
      facilitated the restitution of gastric epithelial cells significantly but did not
      have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA
      was expressed by gastric epithelial cells, indicating that these effects were
      elicited by the specific receptor mediated pathway. Northern blot analysis
      revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric
      epithelial cells, indicating the production of KGF. These results suggest that
      KGF might be involved in gastric mucosal repair, through mesenchymal-epithelial
      interaction.

PMID- 8985837
TI  - Helicobacter pylori infection delays the healing of acetic acid-induced gastric
      ulcer in Japanese monkeys.
AB  - To clarify the relationship between Helicobacter pylori and the healing of
      gastric ulcers, we investigated the healing of acetic acid-induced gastric ulcers
      in the antral mucosa of Japanese monkeys (n = 5) infected with H. pylori and in
      control monkeys without H. pylori infection (n = 6). Using H. pylori-infected
      Japanese monkeys as an experimental model, gastric ulcers were induced
      endoscopically with acetic acid. Healing of ulcers and factors that influenced
      healing were studied. Continuous colonization with H. pylori was confirmed in the
      infected group throughout the observation period; no H. pylori were isolated from
      the gastric mucosa of the control group. White scarring was not observed in any
      infected monkeys 4 weeks after ulcer formation, but was observed in one (20%) of
      five monkeys at 6 weeks and in all five monkeys eight weeks after ulcer
      formation. In the control group, white scarring was observed in one (16.7%) of
      six monkeys at 4 weeks and in six monkeys at 6 (P < 0.01 vs infected group) and 8
      weeks. The ammonia concentration of the gastric secretions and the grade of
      inflammation were significantly increased in the H. pylori-infected group
      compared with the control group (P < 0.01 and P < 0.001, respectively). The
      volume of intracellular PAS-positive substance was decreased (P < 0.025-0.01) at
      the ulcer margin in the infected group compared with the ulcer margin in the
      control group. The proliferation of gastric epithelial cells was markedly
      accelerated at the ulcer margin in the infected group compared with the ulcer
      margin in control group (P < 0.025-0.01). Our results strongly suggest that H.
      pylori infection delays the healing of gastric ulcers.

PMID- 8985838
TI  - Gastrointestinal pH, motility/transit and permeability in cystic fibrosis.
AB  - I reviewed the literature (1966-1994) concerning gastrointestinal (GI) pH,
      motility/transit, and permeability in cystic fibrosis (CF). Most studies reported
      were performed with very small numbers of patients, but even when considered
      together the published data do not confirm some generally expressed views on
      these topics. The only clear findings were a high incidence of gastroesophageal
      reflux in CF; pre- and postprandial duodenal pH is 1-2 U lower in patients with
      CF than in healthy controls; and small intestinal paracellular permeability is 4
      10 times greater than normal in CF. Some patients showed abnormalities of lower
      esophageal sphincter pressure and of esophageal motility, but apart from one case
      study other disturbances of GI motility have not been reported. The results of
      hydrogen breath tests strongly suggest that oro-cecal transit is slowed in CF,
      but these results must be confirmed by an alternative test. Measurements of
      colonic transit and colonic permeability have not been reported. The few studies
      of gastric emptying reported are controversial. Whether GI pH, apart from
      duodenal pH, is normal in CF or whether a subset of patients has exceptionally
      acid intestinal contents requiring specialized pancreatic enzyme supplementation
      to normalize digestion is not clear. Finally, I briefly discuss the findings in
      relation to their possible impact on the pathogenesis of fibrosing colonopathy.

PMID- 8985839
TI  - Increased prevalence of diabetes-related autoantibodies in celiac disease.
AB  - Forty-four nondiabetic patients with celiac disease (CD) were examined for the
      presence of insulin-dependent diabetes mellitus (IDDM)-related autoantibodies.
      Islet cell antibodies (ICA) were detected in 2 of 44 (4.5%). None of the 200 age-
      and sex-matched healthy controls was ICA positive (p < 0.05). Competitive anti
      insulin antibodies (CIAA) were detected in 1 of 44 (2.5%) patients. First-phase
      insulin reserve (FPIR), stimulated insulin reserve (SIR), and glycosylated
      hemoglobin (GHB) levels were normal in the autoantibody-positive patients. Our
      data suggest that, like first-degree relatives of IDDM patients, CD patients are
      characterized by an increased prevalence of diabetes-related autoantibodies.
      Further follow-up is needed to determine whether the presence of these
      autoantibodies in nondiabetic CD patients predicts future IDDM.

PMID- 8985840
TI  - Quality of life in children with Crohn's disease.
AB  - In a 10-week randomised cross-sectional study we used an 88-item questionnaire to
      assess the quality of life in 16 children (ages 8-17 years) with Crohn's disease
      and their families. The questionnaire covered six domains of health-related
      quality of life, including disease and its treatment, social, emotional, family,
      education, and future aspects. Crohn's disease affected education, with
      absenteeism in 12 and distraction during school work in six. Three children had
      had a home tutor, and five stated their need for one. Engaging in sports was a
      problem for eight children, mainly because of a lack of energy in five and the
      presence of a stoma in three children. Three children had missed every PE lesson
      in 1 year. Five children cited the social problem of being unable to stay over at
      friends' houses. Bullying concerned parents more than the children. Holiday
      difficulties included long distance traveling or lack of toilet facilities during
      school trips. Elemental diet was the preferred treatment, although the majority
      complained about the taste. Surgery was the most effective method of symptom
      control, though the resulting stoma was upsetting and restricted sports
      activities. Children on steroids had more depressive symptoms. Using the Rutter A
      Questionnaire, five children were designated "neurotic." Parents' views of the
      severity of symptoms significantly correlated with their children's views
      regarding rectal bleeding, poor growth, lack of energy, and poor appetite (p <
      0.01). The main parental concerns were the side effects of medications and issues
      concerning their children's future, including schooling, job prospects, and
      marriage. The parents of 11 children cited problems with children's behaviour.
      The parents of seven cited disruption of work, and those of six named taking
      holidays. Crohn's disease in children, in addition to being a symptomatically
      disabling condition, has a great impact on the health-related quality of life of
      both sufferers and their parents. The questionnaire was a useful instrument, and
      with some adjustment it can be used again in large group studies.

PMID- 8985841
TI  - Prevalence of antibodies to hepatitis C and herpes simplex virus type 1 is not
      increased in children with liver kidney microsomal type 1 autoimmune hepatitis.

PMID- 8985842
TI  - Surface features of small-intestinal mucosa in childhood diarrheal disorders.
AB  - The pathophysiology of diarrhea, especially in the otherwise healthy child, is
      still poorly understood. The aim of this study was to use the scanning electron
      microscope (SEM) to examine the surface of the jejunal mucosa of children with
      chronic nonspecific diarrhea (CNSD) (n = 9) and to compare the findings with
      specimens obtained from children with (n = 21) and without (n = 11) other
      gastrointestinal diseases. Light microscopy of the specimens from children with
      CNSD was normal. However, SEM showed the presence of bacterial colonization with
      predominantly coccoid organisms in 100% of cases. This colonization was
      associated with loss of glycocalyx and clumping of the microvilli. The children
      with celiac disease (n = 9) all showed characteristic appearances with light
      microscopy, but only one had bacterial colonization on SEM. The surface features
      of specimens from children with other gastrointestinal disorders (food
      intolerance, postenteritis syndrome, protracted diarrhea of infancy, and immune
      deficiency states) were very similar to those from the CNSD group. Bacteria were
      visible on 89% of specimens, and in half of these cases the organisms were
      bacilli. SEM of specimens from children with no gastrointestinal disease (ages 11
      107 months) suggested an increased density of villi/unit area with advancing age.
      Bacteria were present in only two cases and did not include bacilli. The findings
      suggest that bacterial colonization of the surface of the small intestine is
      common in children with several gastrointestinal diseases and may play a part in
      their pathogenesis. Routine SEM examination of jejunal biopsies provides
      information not available from standard light microscopy, which may be relevant
      to the treatment of children with chronic diarrhea.

PMID- 8985843
TI  - HM-PAO-labeled leukocyte scintigraphy in pediatric patients with inflammatory
      bowel disease.
AB  - Leukocyte scintigraphy (LS) was performed in 20 pediatric patients with
      inflammatory bowel disease (IBD: 10 with ulcerative colitis, 2 with indeterminate
      colitis, and 8 with Crohn disease) in different stages of clinical activity.
      Leukocytes were separated from 15 to 60 ml venous blood and were labeled in vitro
      with [99mTc]HM-PAO. The segmental extent (small intestine; ascending, transverse,
      and descending colon; and recto-sigmoideum) of the process was determined by LS.
      The uptake of each bowel segment was scored in relation to the bone marrow
      uptake. The scintigraphic activity, calculated by summing the segment scores, was
      compared with laboratory parameters. The mean labeling efficacy was 76% (60-86%).
      The segmental extent of the process determined by LS was compared with the
      results of barium enema or colonoscopy with regard to 32 bowel segments. The
      sensitivity, specificity, and accuracy of LS were 93, 88, and 91%, respectively.
      Two extraintestinal manifestations (abdominal abscess and joint involvement) were
      also detected by LS. These lesions were verified by computed tomography (CT)
      (abscess) and on the basis of the clinical outcome (arthritis). The scintigraphic
      activity correlated with the C-reactive protein (CRP) level (r = 0.82, p <
      0.001), the alpha 2-globulin level (r = 0.63, p < 0.02), the sedimentation rate
      (r = 0.51, p < 0.05), and the fS iron level (r = -0.66, p < 0.005). LS is
      applicable in pediatric patients. The method is an excellent technique for
      assessment of the extent of IBD in children. Extraintestinal manifestations of
      IBD can also be investigated by LS. The scintigraphic activity is a useful
      parameter for determination of the activity of IBD in children.

PMID- 8985844
TI  - Structural position and amount of palmitic acid in infant formulas: effects on
      fat, fatty acid, and mineral balance.
AB  - The structure of the triglycerides (TG) in human milk (HM) differs from those of
      vegetable oils used in infant formulas. In HM, palmitic acid is predominantly
      esterified to the center or beta-position of the TG, in vegetable oil, it is
      mainly at the external or alpha-positions. These differences in configuration
      affect intestinal fat absorption. Fat and mineral balances were investigated in
      three groups of 9 healthy term infants aged 5 weeks. Infants were randomly
      assigned to receive one of the three study formulas from birth: (a) formula beta,
      resembling the structure of HM fat most closely (24% palmitic acid, 66%
      esterified to beta-position), (b) formula intermediate (24% palmitic acid, 39%
      esterified to the beta-position), and (c) regular formula (20% palmitic acid; 13%
      esterified to the beta-position). Fat absorption was highest in infants fed the
      beta formula (97.6 +/- 0.9%), intermediate in those fed with the intermediate
      formula (93.0 +/- 1.8%), and lowest in infants receiving the regular formula
      (90.4 +/- 4.6%). Fecal calcium excretion was significantly lower in the beta
      group than in the other two groups (43.3 +/- 18.1 vs. 59.9 +/- 15.1 vs. 68.4 +/-
      22.3 mg.kg-1.day-1 for beta, intermediate, and regular respectively). Dietary TG
      containing palmitic acid predominantly at the beta-position, as in HM, have
      significant beneficial effects on the intestinal absorption of fat and calcium in
      healthy term infants.

PMID- 8985845
TI  - Congenital glucose-galactose malabsorption in Arab children.
AB  - Eight children with chronic diarrhea from glucose-galactose malabsorption from
      eight different families are presented. Six children are Saudi Arabs and two are
      of the other Arab nationalities. The mean age of the children at the time of
      presentation was 10.6 months. They were first seen for chronic watery diarrhea,
      present since birth, and failure to thrive. Laboratory investigations, including
      small-bowel biopsy, histology, and small-bowel enzyme assay, confirmed the
      diagnosis of glucose-galactose malabsorption. One child had a renal stone at the
      first visit, and another was discovered to have one on follow-up. All the
      children responded clinically to fructose-based formula, and they are thriving at
      follow-up.

PMID- 8985846
TI  - Liver calcifications in cystic fibrosis.

PMID- 8985847
TI  - Inflammatory bowel disease in infancy: an increasing problem?
AB  - Seven children with intractable diarrhoea of infancy seen between 1990 and 1993
      developed endoscopically established inflammatory bowel disease unrelated to
      bacterial infection and not responsive to whole protein exclusion. Mouth ulcers
      were present in two patients, endoscopic upper-gastrointestinal-tract
      inflammation in two, villous atrophy in six, and chronic nonspecific colitis in
      all seven. There was considerable clinical and histological heterogeneity. All
      patients required parenteral nutrition. Steroid therapy was completely successful
      in only one child, while two underwent colectomy, and two died. Previously
      described cases other than those due to infection or milk intolerance have been
      rare and sporadic. The prevalence of inflammatory bowel disease in infancy is
      unknown but appears to be increasing.

PMID- 8985849
TI  - Colonopathy in a noncystic fibrosis patient: from excess pancreatic enzymes.

PMID- 8985848
TI  - Pneumatosis intestinalis in infants after orthotopic liver transplantation.

PMID- 8985850
TI  - Comparison of oral sodium phosphate to polyethylene glycol-based solution for
      bowel preparation for colonoscopy in children.
AB  - Thirty-four patients, aged 3 to 17 years, were randomized to receive oral sodium
      phosphate solution or a polyethylene glycol-based solution in preparation for
      elective colonoscopy. Nineteen patients received two doses of oral sodium
      phosphate solution (45 mL/1.7 m2/ dose) and 15 received polyethylene glycol-based
      solution (4 L/1.7 m2). Compliance with oral sodium phosphate solution was judged
      as easy or tolerable in 15 of 19 patients, but only in 5 of 15 who were given
      polyethylene glycol-based solution. The quality of colon cleansing was rated by
      an endoscopist who was blinded to the colon preparation method used. The bowel
      preparation was excellent or good (only liquid remaining in the colonic lumen) in
      18 of 19 patients who received oral sodium phosphate solution and in 6 of 15 who
      received polyethylene glycol-based solution. The incidence of vomiting was
      similar in both groups, but abdominal pain occurred more frequently in the
      polyethylene glycol-based solution group. Hyperphosphatemia developed in patients
      who received oral sodium phosphate solution (serum phosphorus = 2.3 +/- 0.7
      mmol/L (7.2 +/- 2.2 mg/dL; mean +/- SD), but only in 1 of 15 patients in the
      polyethylene glycol-based solution group. Patients did not exhibit symptoms of
      hyperphosphatemia and serum calcium concentrations were similar in both groups.
      In summary, oral sodium phosphate solution is better tolerated than polyethylene
      glycol-based solution for bowel preparation in children. However,
      hyperphosphatemia occurred frequently in patients who received oral sodium
      phosphate solution. Further studies are needed to determine the optimal dose for
      safety and efficacy for the use of these solutions in children.

PMID- 8985852
TI  - Magnetic resonance imaging for diagnosis of Shwachman's syndrome.
AB  - Shwachman's syndrome is a rare disease characterized by the association of
      chronic diarrhea due to exocrine pancreatic insufficiency, metaphyseal
      dysostosis, and neutropenia. The diagnosis requires demonstration of lipomatosis,
      or fatty replacement of the pancreas, which is the typical pathological feature
      of the disease. Magnetic resonance imaging (MRI) was performed in 13 patients
      with exocrine pancreatic insufficiency, 7 with Shwachman's syndrome, 2 with
      Pearson's syndrome, 1 with normal sweat test later diagnosed as cystic fibrosis,
      and 3 without identified syndrome, and in 7 control children. Ultrasonography in
      the patients did not differentiate between atrophy and lipomatosis and could not
      be performed in 3. MRI visualized the pancreas in all. The same image was noted
      in all patients with Shwachman's syndrome with a normal-sized or enlarged
      pancreas, a hyperintense signal on T1- and T2-weighted image, and a null signal
      on short time inversion recovery (STIR)-weighted image, characteristic of fat. In
      all other patients, the findings were very different: The pancreas was a small
      structure surrounded with fat. In 1 patient without identified syndrome, the
      pancreas appeared to be partially replaced with fat. MRI is an excellent imaging
      technique to correlate the nature of a tissue and its radiological
      representation, especially fat, which gives a very typical signal. In our brief
      series of patients with Shwachman's syndrome, MRI had 100% positive predictive
      value in demonstrating lipomatosis. In atypical cases of pancreatic insufficiency
      in which some of the clinical features of Shwachman's syndrome are absent. MRI is
      an invaluable aid in the diagnostic procedure.

PMID- 8985851
TI  - Gastroesophageal reflux in infants: evaluation of a new intraluminal impedance
      technique.
AB  - In this study, pH metry was simultaneously applied with a new technique, the
      intraluminal multiple electrical impedance (IMP) procedure, for measuring
      gastrointestinal motility for gastroesophageal reflux (GER) detection. Seventeen
      infants with clinical symptoms of GER disease such as recurrent apnea, aspiration
      pneumonia, wheezing, and failure to thrive were investigated during two feeding
      periods. A single catheter combining a pH electrode with seven electrodes for
      impedance measurements over a distance of 8.5 cm was used for the investigation.
      In all patients, 185 acid episodes were detected by pH metry. In 106 of these 185
      acid episodes, a unique pattern in the IMP readings was noted, indicated by a
      retrograde esophageal volume flow. These episodes were regarded as acid GER
      episodes. Seventy-one of the 185 acid episodes occurred during the clearance
      process of a preceding acid GER characterized by typical IMP readings of an
      anterograde bolus transport. Eight of 185 acid episodes were missed in the IMP
      readings for technical reasons. The IMP pattern described as characteristic for a
      GER was observed in 490 other episodes not detected by pH metry. More than 75% of
      all GER detected by IMP reached the pharyngeal space; 73% of all GER occurred
      during feeding and the first 2 postprandial hours and 27% occurred during the
      remaining time until the next feeding. Even during the latter period, 34% of GER
      were detected by IMP only; they were missed by pH metry. Volume clearance
      indicated by IMP was always completed earlier than acidity clearance. The results
      show that IMP technique facilitates the detection of all GER, whereas pH metry is
      confined to the measurement of acid GER. Therefore, this technique might improve
      the evaluation of GER disease and detection of GER in conditions with gastric
      hypoacidity.

PMID- 8985853
TI  - Neonatal and infantile upper gastrointestinal endoscopy using a new small
      diameter fibreoptic gastroscope.
AB  - Using a new prototype (Olympus XPGIF 5.2/ N30) gastroscope, upper
      gastrointestinal endoscopy was safely performed under sedation on 99 infants
      (weights 0.9 to 10.1 kg). No complications occurred. Macroscopic and microscopic
      abnormalities were found in 60%, including abnormal duodenal biopsies in 47% of
      cases with protracted diarrhoea. Duodenal biopsy material was, however, of
      suboptimal standard for histologic assessment in 25% of the cases. In 52% of
      those under 3.5 kg diagnoses were made that would not have otherwise been
      possible and, in 75% of those in the Intensive Care Unit, abnormalities were
      found. The use of this new endoscope represents a significant advance in clinical
      practice.

PMID- 8985854
TI  - Superoxide dismutase activity in Helicobacter pylori-positive antral gastritis in
      children.
AB  - Reactive oxygen metabolites have been implicated in gastric mucosal injuries.
      Superoxide dismutase, a scavenger of superoxide radical, is a key enzyme in
      gastric mucosal protection against several damaging factors. This study was aimed
      at investigating the relationship of superoxide dismutase activity to
      Helicobacter pylori-induced antral gastritis in children. Two groups of 11
      children each, one positive and the other negative for Helicobacter pylori, were
      studied. Biopsies from the antrum and corpus were obtained for evaluation of
      Helicobacter pylori by CLOtest and histology as well as for superoxide dismutase
      activity (cytochrome c method). Erythrocytic and serum superoxide dismutase
      levels were determined as well. Superoxide dismutase activity was significantly
      higher only in the antrum of children with Helicobacter pylori-induced antral
      gastritis. There was no significant difference in superoxide dismutase activity
      in the corpus, erythrocytes, or serum of both groups. These findings may suggest
      a pathogenic relationship between the presence of Helicobacter pylori and oxygen
      radicals in inducing antral mucosal injury.

PMID- 8985856
TI  - Le foie vide: a unique case of neonatal liver failure.

PMID- 8985857
TI  - Endoscopic retrograde cholangiopancreatography in children with HIV infection.

PMID- 8985855
TI  - Endoscopic biliary sphincterotomy and stone extraction in a child with
      choledocholithiasis complicating Byler's disease.

PMID- 8985858
TI  - Toothpick foreign body perforation and migration mimicking Crohn's disease in a
      child.

PMID- 8985859
TI  - Urinary lactose excretion increases with estimated milk production.

PMID- 8985860
TI  - Mechanisms for signal transformation in lemniscal auditory thalamus.
AB  - 1. During alertness, lemniscal thalamocortical neurons in the ventral medial
      geniculate body (MGBv) encode sound signals by firing action potentials in a
      tonic mode. When they are in a burst firing mode, characteristic of thalamic
      neurons during some sleep states, the same stimuli may have an alerting function,
      leading to conscious perception of sound. We investigated the intrinsic membrane
      properties of MGBv neurons in search of mechanisms that enable them to convert
      from burst to tonic firing modes, allowing accurate signal coding of sensory
      stimuli. 2. We studied thalamocortical relay neurons and identified neurons
      morphologically with injected N-(2-aminoethyl) biotinamide hydrochloride in in
      vitro slice preparations of young rats. With the use of the whole cell recording
      method, we examined the contributions of distinct conductances to voltage
      responses evoked by current pulses. The neurons (n = 74) displayed a narrow range
      of resting potentials (-68 +/- 4 mV, mean +/- SD) and an average input resistance
      of 226 +/- 100 M omega. The membrane time constant was 40 +/- 17.6 ms and the
      action potential threshold was -51.6 +/- 3 mV. 3. Injections of hyperpolarizing
      current pulses from rest revealed an inward rectification produced by two voltage
      dependent components. A fast component, sensitive to blockade with Ba2+ (100-200
      microM), was attributed to an inward rectifier, IIR. Such applications also
      increased input resistance and depolarized neurons, consistent with a blockade of
      various K+ conductances. Application of Ba2+ often unmasked another voltage
      dependent rectification with a slower time course. The second component was
      sensitive to blockade with Cs+ (1.5 mM), reminiscent of a hyperpolarization
      activated current, IH. 4. Depolarizing pulses from rest produced ramp-shaped
      voltage responses that led to delayed tonic firing. Blockade of Na+ conductances
      by tetrodotoxin (TTX, 300-600 nM), or extracellular replacement of Ca2+ with Mg2+
      (with TTX present), reduced the slope of the ramp and the overall depolarizing
      response. Application of 4-aminopyridine (4-AP, 100 microM), a blocker of A-type
      K+ conductances, increased input resistance and the overall depolarizing
      response. The voltage ramp therefore represents a complex rectification due to
      voltage-dependent contributions of persistent Na-, Ca2+, and K+ conductances. 5.
      Depolarizing pulses from potentials of less than -75 mV evoked phasic burst
      responses, consisting of one to seven action potentials riding on a low-threshold
      spike (LTS). The LTS was absent in low extracellular Ca2+ conditions and was
      blocked by application of Ni2+ (0.6 mM), but not by Cd2+ (50 microM). Similar
      depolarization from less than -80 mV evoked several action potentials, often
      followed by a TTX-resistant high-threshold spike (HTS) of longer duration. Firing
      of HTSs always occurred during 4-AP (100 microM) application, inferring that,
      normally, A-type K+ conductances may control ability to fire an HTS. As in the
      LTS, a Ca2+ current is a major participant in the HTS because extracellular
      replacement of Ca2+ with Mg2+ or application of Cd2+ (50 microM) blocked its
      genesis. After TTX blockade of Na+ conductances, "tonic firing" of HTSs occurred
      during depolarization above -45 mV. 6. During tonic firing evoked by current
      pulses, the second and subsequent spikes were longer in duration than the initial
      action potentials. Low extracellular concentrations of Ca2+ or Cd2+ (50 microM)
      application reduced the durations of the nonprimary spikes, inferring a
      contribution of high-threshold voltage-dependent Ca2+ conductances to their
      repolarizing phase. Also, K+ conductances may contribute to spike repolarization,
      because 4-AP (100 microM) or tetraethylammonium (2 mM) application led to
      prolonged action potentials and the generation of plateau potentials. A fast
      afterhyperpolarization, likely mediated by a Ca(2+)-dependent K+ conductance,
      limited the tonic firing. Such conductances, therefore, may regulate the re

PMID- 8985861
TI  - Activation of the protein phosphatase calcineurin during carbachol exposure
      decreases the extent of recovery from end-plate desensitization.
AB  - 1. Our previous studies demonstrated that protein kinase C (PKC) activity is
      required for acetylcholine (ACh) sensitivity to recover fully at snake twitch
      fiber end plates after prolonged exposure to carbachol. In the present studies,
      we have investigated whether protein phosphatase(s), activated during carbachol
      exposure, dephosphorylated critical membrane proteins, which required
      rephosphorylation by PKC to maintain end-plate sensitivity. End-plate sensitivity
      was assessed from measurements of miniature end-plate currents (MEPCs) and
      carbachol-activated currents (EPCCARBS). Conductance of ACh-activated channels
      was determined from patch-clamp recordings of single-channel currents. 2.
      Pretreatment of snake muscle preparations with the protein kinase inhibitor
      staurosporine (0.5 microM), followed by a 10-min exposure to 540 microM
      carbachol, reduced mean MEPC amplitudes to values 30-40% less than those recorded
      before carbachol exposure. Conversely, at control end plates exposed to
      carbachol, the mean MEPC amplitude was reduced by only approximately 5% compared
      with precarbachol values. This staurosporine-induced decrease in ACh sensitivity
      could be prevented by pretreatment with the protein phosphatase 2B (calcineurin)
      inhibitor deltamethrin (0.5 microM), whereas okadaic acid (5 microM) and
      calyculin A (0.5 microM), inhibitors of protein phosphatases 1 and 2A, had no
      effect. 3. After a 10-min exposure to 540 microM carbachol, EPCCARB amplitudes
      (produced by local superfusion with 20 microM carbachol) were significantly
      smaller at staurosporine-treated end plates than at control end plates. In
      contrast, the EPCCARB amplitude recorded from end plates pretreated with both
      deltamethrin and staurosporine was not significantly different from that recorded
      at control end plates. 4. Substitution of 10 mM Mn2+ for external Ca2+ during the
      exposure to 540 microM carbachol prevented the decrease in MEPC amplitude
      recovery at staurosporine-treated end plates. These results suggested that the
      alteration in sensitivity at staurosporine-treated end plates was calcium
      dependent. 5. At control end plates, a single population of ACh-activated
      channels (45-50 pS) is observed both before and after a 10-min exposure to 540
      microM carbachol. Conversely, at staurosporine-treated end plates, after exposure
      to carbachol, a second population of small-conductance (25-30 pS) ACh-activated
      channels is present in addition to the predominant 45- to 50-pS ACh-activated
      channels. In preparations pretreated with both deltamethrin and staurosporine,
      after carbachol exposure, there was a significant decrease in the frequency of
      small-conductance ACh-activated channels. Deltamethrin treatment alone produced
      no small-conductance channels before or after a 10-min exposure to 540 microM
      carbachol. Also, no small-conductance ACh-gated channels were recorded at PKC
      inhibited end plates after carbachol exposure either with pretreatment with 10
      microM cyclosporin A (another inhibitor of calcineurin) or with the substitution
      of 10 mM Mn2+ for Ca2+ during the 10-min agonist exposure. 6. We propose that
      during prolonged exposure to the nicotinic agonist carbachol, calcium influx
      through ACh-gated channels elevates the level of ionized calcium at the inner
      surface of the post-junctional membrane and that this local rise in intracellular
      calcium activates the calcium-dependent phosphatase calcineurin.
      Dephosphorylation of some key membrane protein by calcineurin leads to a decrease
      in the extent of recovery from desensitization. Under normal conditions, this
      process is effectively reversed by PKC activity and end-plate sensitivity
      recovers fully. However, when PKC is inhibited, the extent of recovery of end
      plate sensitivity is decreased, and associated with this decrease is the presence
      of small-conductance ACh-activated channels not normally recorded at snake twitch
      fiber end plates.

PMID- 8985863
TI  - Parallel processing in cerebral cortex of the marmoset monkey: effect of
      reversible SI inactivation on tactile responses in SII.
AB  - 1. Responsiveness within the hand region of the second somatosensory area of
      cortex (SII) was investigated in the marmoset monkey (Callithrix jacchus) in
      association with cooling-induced, reversible inactivation of the primary
      somatosensory area, SI. The aims were to determine whether thalamocortical
      systems in this primate species are organized according to a serial scheme in
      which tactile information is conveyed from the thalamus to SI and thence to SII
      as the next hierarchical level of processing and to establish whether primates
      are fundamentally different, in this respect, from mammals in which tactile
      information is conveyed in parallel from the thalamus to both SI and SII. 2.
      Inactivation of the SI had area was achieved when the temperature at the face of
      the silver cooling block over this SI region was lowered to < or = 13 degrees C.
      Inactivation was confirmed by abolition of the SI surface potential evoked by a
      brief tap stimulus to the hand and by the abolition of responsiveness in single
      SI neurons located beneath and around the edge of the block. 3. The effect of SI
      inactivation on SII-evoked potentials was investigated in 20 experiments by
      simultaneous recording of the SI- and SII-evoked potentials. The SII response was
      never abolished and was unchanged in the majority (12/20) of experiments. In the
      remainder, the SII-evoked potentials underwent a reduction in amplitude that was
      usually < 30% but never > 50%. 4. Tactile responsiveness was examined
      quantitatively in 47 individual SII neurons of different functional classes
      before, during, and after the inactivation of SI. Controlled tactile stimuli
      consisted of trains of sinusoidal vibration or rectangular pulses delivered to
      the glabrous or hairy skin of the hand. 5. Thirteen of the 47 SII neurons (28%)
      were unaffected in their response levels in association with SI inactivation. The
      remaining 34 SII neurons underwent some reduction in responsiveness, but in only
      6% (3/47) was responsiveness abolished by SI inactivation. As the same range of
      functional classes of tactile neurons were represented among the affected and
      unaffected SII neurons, there was no evidence for a differential susceptibility
      among SII tactile neurons to the effect of SI inactivation. 6. Where reductions
      in amplitude of the SII-evoked potential or in response levels of SII neurons
      were observed, the effects were not attributable to direct spread of cooling from
      SI to the SII hand area as there was no cooling-induced prolongation of either
      the evoked potential or spike waveform in SII, an effect that is known to precede
      cooling-induced reductions in responsiveness. 7. These lines of evidence indicate
      that reductions in SII responsiveness in association with SI inactivation may be
      attributable to a loss of a background facilitatory influence rather than to a
      blockage of a component of peripheral input that comes over a putative serial
      path to SII via SI. First, as SI was cooled, there was a progressive increase in
      latency and time course of the SI responses before their disappearance, but no
      comparable delay in the SII responses as might be expected if SI were placed
      earlier than SII in a strict hierarchical scheme of thalamocortical processing.
      Second, SI inactivation failed to bring about a tightening in the phase-locking
      of SII responses to vibrotactile stimuli as might have been expected if the
      inputs to the SII neurons come via both a direct path from the thalamus and an
      indirect intracortical path via SI. Blockage of the indirect intracortical
      pathway through SI might be expected to reduce temporal dispersion in the input
      to SII neurons and result in an improvement in phase-locking in the SII responses
      to skin vibration. Third, the background activity of some SII neurons was reduced
      during SI inactivation along with the reduction in their responses to tactile
      stimulation.

PMID- 8985862
TI  - Saccades to remembered targets: the effects of smooth pursuit and illusory
      stimulus motion.
AB  - 1. Measurements were made in four normal human subjects of the accuracy of
      saccades to remembered locations of targets that were flashed on a 20 x 30 deg
      random dot display that was either stationary or moving horizontally and
      sinusoidally at +/-9 deg at 0.3 Hz. During the interval between the target flash
      and the memory-guided saccade, the "memory period" (1.4 s), subjects either
      fixated a stationary spot or pursued a spot moving vertically sinusoidally at +/
      9 deg at 0.3 Hz. 2. When saccades were made toward the location of targets
      previously flashed on a stationary background as subjects fixated the stationary
      spot, median saccadic error was 0.93 deg horizontally and 1.1 deg vertically.
      These errors were greater than for saccades to visible targets, which had median
      values of 0.59 deg horizontally and 0.60 deg vertically. 3. When targets were
      flashed as subjects smoothly pursued a spot that moved vertically across the
      stationary background, median saccadic error was 1.1 deg horizontally and 1.2 deg
      vertically, thus being of similar accuracy to when targets were flashed during
      fixation. In addition, the vertical component of the memory-guided saccade was
      much more closely correlated with the "spatial error" than with the "retinal
      error"; this indicated that, when programming the saccade, the brain had taken
      into account eye movements that occurred during the memory period. 4. When
      saccades were made to targets flashed during attempted fixation of a stationary
      spot on a horizontally moving background, a condition that produces a weak
      Duncker-type illusion of horizontal movement of the primary target, median
      saccadic error increased horizontally to 3.2 deg but was 1.1 deg vertically. 5.
      When targets were flashed as subjects smoothly pursued a spot that moved
      vertically on the horizontally moving background, a condition that induces a
      strong illusion of diagonal target motion, median saccadic error was 4.0 deg
      horizontally and 1.5 deg vertically; thus the horizontal error was greater than
      under any other experimental condition. 6. In most trials, the initial saccade to
      the remembered target was followed by additional saccades while the subject was
      still in darkness. These secondary saccades, which were executed in the absence
      of visual feedback, brought the eye closer to the target location. During
      paradigms involving horizontal background movement, these corrections were more
      prominent horizontally than vertically. 7. Further measurements were made in two
      subjects to determine whether inaccuracy of memory-guided saccades, in the
      horizontal plane, was due to mislocalization at the time that the target flashed,
      misrepresentation of the trajectory of the pursuit eye movement during the memory
      period, or both. 8. The magnitude of the saccadic error, both with and without
      corrections made in darkness, was mislocalized by approximately 30% of the
      displacement of the background at the time that the target flashed. The magnitude
      of the saccadic error also was influenced by net movement of the background
      during the memory period, corresponding to approximately 25% of net background
      movement for the initial saccade and approximately 13% for the final eye position
      achieved in darkness. 9. We formulated simple linear models to test specific
      hypotheses about which combinations of signals best describe the observed
      saccadic amplitudes. We tested the possibilities that the brain made an accurate
      memory of target location and a reliable representation of the eye movement
      during the memory period, or that one or both of these was corrupted by the
      illusory visual stimulus. Our data were best accounted for by a model in which
      both the working memory of target location and the internal representation of the
      horizontal eye movements were corrupted by the illusory visual stimulus. We
      conclude that extraretinal signals played only a minor role, in comparison with
      visual estimates of the direction of gaze, in planning eye movements to
      remembered targ

PMID- 8985864
TI  - Cooling-specific spinothalamic neurons in the monkey.
AB  - 1. Little is known concerning the processing of innocuous thermoreceptive
      information in the CNS of the monkey. The aim of the present study was to confirm
      the prediction, based on recent studies in cat and monkey, that there must be a
      prominent spinothalamic (STT) projection of cooling-specific spinal cord lamina I
      neurons to the posterior part of the ventral medial nucleus (VMpo) of the monkey
      thalamus. 2. Experiments were performed on four cynomolgus monkeys anesthetized
      with pentobarbital sodium. A detailed mapping of somatosensory thalamus was
      performed in each animal, and VMpo was identified by recordings from clusters of
      thermoreceptive-specific and nociceptive-specific (NS) neurons. Stimulating
      electrodes were then implanted in VMpo. Tungsten microelectrodes were used to
      record the responses of neurons in the superficial dorsal horn of the lumbosacral
      spinal cord. 3. Many spontaneously active lamina I neurons were found that were
      inhibited by radiant warming and that responded to innocuous cooling of the
      hindpaw. These cooling-specific (COLD) neurons were excited by small temperature
      drops below skin temperature and increased their discharge with decreasing skin
      temperature. They were not excited by thermally neutral mechanical stimuli
      applied to the receptive fields. In passing, we also characterized with natural
      stimulation a few NS neurons reponsive to pinch and/ or noxious heat, multimodal
      (HPC) neurons responsive to noxious heat, pinch, and cold stimuli, and wide
      dynamic-range neurons responsive to both innocuous and noxius cutaneous stimuli
      that were encountered in lamina I. 4. Twenty lamina I COLD cells were identified
      as STT neurons by antidromic activation from the contralateral VMpo. The mean
      conduction latency for these units was 26.1 ms, which corresponds to a mean
      conduction velocity of approximately 8.0 m/s. They were not antidromically
      activated from an electrode in the region of the ventral posterior nucleus in the
      thalamus. In addition, we antidromically activated from VMpo four NS units and
      three HPC cells. 5. These findings demonstrate for the first time the existence
      of a prominent direct projection of specific COLD lamina I STT cells to thalamus
      in the monkey. This is consistent with clinical inferences in humans and with
      prior results in cats. This result confirms that the dense lamina I STT
      projection to VMpo demonstrated in anatomic studies includes COLD cells, and it
      supports the role of VMpo as a thalamic relay nucleus for pain- and temperature
      related information.

PMID- 8985865
TI  - Saccadic reaction time in the monkey: advanced preparation of oculomotor programs
      is primarily responsible for express saccade occurrence.
AB  - 1. The introduction of a period of darkness between the disappearance of an
      initial fixation target and the appearance of a peripheral saccade target
      produces a general reduction in saccadic reaction time (SRT)-known as the gap
      effect- and often very short latency express saccades. To account for these
      phenomena, premotor processes may be facilitated by release of visual fixation
      and advanced preparation of saccadic programs. The experiments described in this
      paper were designed to test the relevance of the ocular fixation disengagement
      and oculomotor preparation hypotheses by identifying the influence of different
      factors on SRTs and the occurrence of express saccades in the monkey. 2. The SRTs
      of two monkeys were measured in two behavioral paradigms. A peripheral saccade
      target appeared at the time of disappearance of a central fixation target in the
      no-gap task, whereas a 200-ms period of no stimuli was interposed between the
      fixation target disappearance and the saccade target appearance in the gap task.
      The distribution of SRTs in these tasks was generally bimodal; the first and
      second mode was composed of express and regular saccades, respectively. We
      measured the mean SRT, mean regular saccade latency, mean express saccade
      latency, and percentage of express saccades in both tasks. We also estimated the
      gap effect, i.e., the difference between the SRTs in no-gap trial and the SRTs in
      gap trials. 3. Once the animals were trained to make saccades to a single target
      location and produce express saccades, SRTs in both no-gap and gap trials
      displayed a broad tuning with respect to the spatial location of the trained
      target when the target location was varied randomly in a block of trials. Express
      saccades were made only to a restricted region of the visual field surrounding
      the trained target location. A gap effect was present for nearly all target
      locations tested, irrespective of express saccade occurrence. Finally, the
      probability of generating an express saccade at the trained target location
      decreased with the introduction of uncertainty about target location. 4. The
      occurrence of express saccades increased with the duration of the visual and
      nonvisual (gap) fixation that the animal was required to maintain before the
      onset of a saccade target. The gap duration was effective in reducing the mean
      SRT for gaps < or = 300 ms, and it was more influential than comparable variation
      in the visual fixation duration. 5. The occurrence of express saccades made to
      targets of identical eccentricity increased when the initial eye fixation
      position was shifted eccentric in a direction opposite to the saccade direction.
      Concomitantly, mean SRT decreased by approximately 2 ms for each 1-deg change in
      initial eye fixation position. 6. The occurrence of express saccades depended
      upon contextual factors, i.e., on both the behavioral task (no-gap or gap) and
      the latency of the saccade that the monkey executed to the same target in the
      preceding trial. The highest percentage of express saccades was observed after an
      express saccade in a no-gap trial, whereas the lowest percentage was obtained
      after a regular saccade in a gap trial. 7. These findings indicate that training
      dependent express saccades are restricted to a specific spatial location dictated
      by the training target, and their incidence is facilitated by high predictability
      of target presentation, long-duration foreperiod, absence of visual fixation,
      eccentric initial eye position opposite to the saccade direction, and express
      saccade occurrence in the previous trial. The release of fixation afforded by the
      gap accounts for the general gap effect, but has only a modulatory influence on
      express saccade generation. We conclude that advanced motor preparation of
      saccadic programs generally reduces SRT and is primarily responsible for the
      occurrence of express saccades, which therefore may be caused mainly by neuronal
      changes restricted to a specific locus-coding for the trained movemen

PMID- 8985866
TI  - Representation of frequency in the primary auditory field of the barn owl
      forebrain.
AB  - 1. The primary auditory field (PAF) constitutes the first telencephalic stage of
      auditory information processing in the classical auditory pathway. In this study
      we investigated the frequency representation in the PAF of the barn owl, a
      species with a broad frequency range of hearing and a highly advanced auditory
      system. 2. Single- and multiunit sites were recorded extracellularly in ketamine
      anesthetized owls. The frequency response properties of PAF sites were assessed
      with the use of digitally synthesized dichotic stimuli. PAF sites (n = 442)
      either were unresponsive to tonal stimulation (but responsive to noise stimuli),
      were tuned for frequency, or had multipeaked frequency response profiles. Tuned
      sites responded best to frequencies between 0.2 and 8.8 kHz, a range that
      encompasses nearly the entire hearing range of the barn owl. Most sites
      responding best to frequencies < 4 kHz had relatively broad frequency tuning,
      whereas sites responding best to higher frequencies had either broad or narrow
      frequency tuning. Sites with multipeaked frequency response profiles typically
      had two response peaks. The first peak was usually between 1 and 3 kHz and the
      second was usually between 5 and 8 kHz; there was no systematic relationship
      between the two peak frequencies. 3. In dorsoventral electrode penetrations that
      contained sites with tuned and/or multipeaked response profiles, a "common
      frequency" was identified that elicited a maximal response from all of the sites
      in the penetration. 4. The PAF contains a single tonotopic field. Units tuned to
      low frequencies are located caudomedially, whereas units tuned to high
      frequencies are located rostrolaterally. Compared with the frequency
      representation along the basilar papilla and in other auditory structures, the
      PAF overrepresents low frequencies (< 4 kHz) that are important for barn owl
      vocalizations. Conversely, high frequencies (> or = 4 kHz), which are necessary
      for precise sound localization, are underrepresented relative to these more
      peripheral auditory structures. 5. There was considerable interindividual
      variability both in the relative magnification of different frequency ranges and
      in the orientation of the tonotopic map in the brain. 6. These results suggest
      that the barn owl PAF, like the mammalian primary auditory cortex, is a general
      processor of auditory information that is involved in the analysis of both the
      meaning (such as species-specific vocalizations) and the location of auditory
      stimuli. In addition, the high degree of interindividual variability in the
      representation of frequency information suggests that the barn owl PAF, like the
      mammalian auditory cortex, is subject to modification by sensory experience.

PMID- 8985867
TI  - Overarm throws with the nondominant arm: kinematics of accuracy.
AB  - 1. Overarm throws made with the nondominant arm are usually less accurate than
      those made with the dominant arm. The objective was to determine the errors in
      the joint rotations associated with this inaccuracy, and thereby to gain insight
      into the neural mechanisms that contribute to skill in overarm throwing. 2.
      Overarm throws from both left and right arms were recorded on different occasions
      as six right-handed subjects sat with a fixed trunk and threw 150 tennis balls at
      about the same speed at a 6-cm square on a target grid 3 m away. Joint rotations
      at the shoulder, elbow, wrist, and finger, and arm translations, were computed
      from recordings of arm segment orientations made with the magnetic-field search
      coil technique. 3. All subjects threw less accurately in this task with the left
      (nondominant) arm. For throws made with the left arm, the height of ball impact
      on the target grid was related to hand trajectory length and to hand orientation
      in space at ball release, but not to hand trajectory height. 4. Two hypotheses
      were proposed to explain the decreased ball accuracy in the high-low direction
      during throwing with the nondominant arm: that it was caused by increased
      variability in the velocity or timing of onset of rotations at proximal joints
      (which determine the path of the hand through space) or increased variability in
      the velocity or timing of onset of finger extension (which determine the moment
      of ball release). 5. A prediction of the first hypothesis was that proximal joint
      rotations should be more variable in throws with the left arm. This was the case
      for the majority of proximal joint rotations in the six subjects when variability
      was examined in joint space. However, some proximal joint rotations were more
      variable in the right arm. 6. The first hypothesis was directly tested by
      determining whether hand angular position in space (which represents the sum of
      all proximal joint rotations) was related to ball impact height on the target
      grid at a fixed translational position in the throw. No relation was found
      between these variables for throws with the left arm in four subjects, whereas a
      weak relation was found for two subjects. It was concluded that, considering all
      subjects, the first hypothesis could not explain the results. 7. In contrast, in
      agreement with the second hypothesis, a strong relation (P < 0.001) was found in
      all subjects between ball impact height on the target grid and time of ball
      release for throws with the left arm, and with time of onset of finger extension.
      8. Across all six subjects the timing precision (windows) for 95% of the throws
      was (for ball release) right arm, 9.3 ms; left arm, 22.5 ms; (for onset of finger
      extension) right arm, 13.7 ms; left arm, 26.7 ms. 9. Timing of onset of finger
      extension was no less accurate than timing of onset of other joint rotations for
      both left and right arms. However, simulations of throws showed that, for the
      same error in timing, finger extension had twice as large an effect on ball
      direction as any other joint rotation. Timing errors at the fingers have a
      greater effect than errors at other joints because finger errors are scaled by
      the higher angular velocity of the hand in space rather than by the smaller
      angular velocities of the individual joints. 10. It is concluded that although
      rotations were in general more variable at both proximal and distal joints of the
      nondominant (left) arm, the major cause of its decreased throwing accuracy was
      increased variability at the distal joints, i.e., in the timing of onset of
      finger extension. This may be due to a lack of precision in the commands from the
      right hemisphere to the left fingers in right-handed throwers.

PMID- 8985868
TI  - Response compatibility and the relationship between event-related potentials and
      the timing of a motor response.
AB  - 1. Earlier studies have shown that changes in the difficulty of sensory
      discrimination in a choice reaction time task result in a prolongation of the
      peak latency for several components of the long-latency event-related potential
      (ERP). With the use of the technique of response-locked averaging, we have
      previously shown that manipulation of the difficulty of sensory discrimination
      also affects response execution as assessed by the interval between the ERP and
      onset of the response. In the present paper we examine the hypothesis that
      changing the compatibility of the responses may also affect the difficulty of the
      discrimination, as well as the execution of the response, as assessed by the
      interval between stimulus onset and the ERP. Such an effect of response
      compatibility would provide further evidence for the close integration of motor
      and sensory processes in the performance of choice reaction time tasks. 2. We
      continuously recorded the electroencephalogram (EEG) from the scalp and the
      electromyogram (EMG) from the responding muscles in both compatible and
      noncompatible visual choice reaction time tasks. In the compatible task subjects
      responded to a lateralized visual stimulus with the hand ipsilateral to the
      stimulus, whereas in the noncompatible task they responded with the contralateral
      hand. EEG and EMG responses were analyzed and averaged off-line, aligning the
      waveforms by either stimulus onset (stimulus-synchronized averages) or response
      onset (response-synchronized averages), and averaged separately for both correct
      and incorrect response outcomes. 3. Response times were significantly faster for
      frequent stimuli than rare stimuli and were significantly faster to rare stimuli
      in the compatible than the noncompatible condition. In responses to the frequent
      stimuli (where both hands were required to respond), the right hand was slightly
      but consistently faster than the left hand. The right hand also accounted for 83%
      of the errors made. 4. Stimulus-synchronized and response-synchronized ERPs to
      either frequent or rare stimuli had a similar appearance for correct responses in
      both the compatible and noncompatible conditions. The coupling of the response to
      the ERP for the rare stimuli, however, was different for the two conditions: the
      response occurred later relative to the ERP components in the response
      synchronized average in the noncompatible condition compared with the compatible
      condition. By contrast, the coupling of the ERPs to the onset of the stimulus was
      the same in the two conditions. 5. Stimulus-synchronized averages for error
      responses in which the rare tone was mistaken for a frequent tone showed early
      sensory processing (as judged by the ERPs) that was similar to that of correct
      responses to the rare stimuli. After the apparent positive (P2) component of the
      cerebral response, however, the processing differed, with a superimposed broad
      negativity possibly reflecting awareness by the subject that a mistake had been
      made. By contrast, the response-synchronized averages for these error trials
      appeared like those to frequent stimuli, with the response being coupled to the
      P2 component of the cerebral response. 6. These results suggest that response
      compatibility affects response selection processes but does not alter sensory
      discrimination. However, despite the similarly tight coupling of the response to
      the ERP in both the compatible and noncompatible conditions, the response
      occurred later relative to the ERPs in the noncompatible condition. This suggests
      that different components of the ERP are responsible for triggering the response
      in different circumstances. Our observations on the error trials suggests that
      the decision to respond (on these trials) is based on the occurrence of cerebral
      events that are evoked by either rare or frequent stimuli, whereas this decision
      (on correct response trials) is based on cerebral events elicited only by the
      rare stimuli.

PMID- 8985869
TI  - NREM delta stimulation following MK-801 is a response of sleep systems.
AB  - 1. We have previously shown that noncompetitive blockade of the N-methyl-D
      aspartate (NMDA)-gated cation channel with ketamine or Dizocilpine maleate (MK
      801) increases the intensity of non-rapid-eye-movement (NREM) delta during
      subsequent sleep. This delta increase [measured as integrated amplitude (IA) in 1
      to 4-Hz electroencephalogram (EEG)] occurs in the 12-h period following
      intraperitoneal injection. However, the 12 h after drug injection is also the
      period in which these drugs induce neurotoxic changes, raising the possibility
      that the increased delta represents toxic EEG slowing rather than an increase in
      the physiological delta waves of NREM sleep. 2. We hypothesized that the time
      course of delta stimulation could be separated from the time course of
      neurotoxicity. We tested this hypothesis by injecting 0.3 mg/kg MK-801 at the
      start of the dark period (DP) and depriving rats of sleep until the onset of the
      light period (LP) 12 h later. 3. There were two control groups: one received MK
      801 at the start of the DP with no further manipulation, and the second received
      a saline injection at DP onset followed by 12 h of sleep deprivation. The
      dependent variable was the amount of delta IA in the LP, whose onset was 12 h
      after MK-801 injection. Total IA in the LP was significantly greater in rats that
      received MK-801 followed by sleep deprivation than in rats that received sleep
      deprivation alone or MK-801 alone. 4. This finding indicates that delta
      stimulation by MK-801 is maintained over 12 h of waking, indicating that the
      delta increase is not due to toxic EEG slowing or persisting MK-801. Instead,
      NMDA channel blockade by MK-801 increases the homeostatic need for delta or else
      directly alters sleep regulatory systems. We speculate that these effects are
      mediated by hypothalamic sleep centers through control of neuroendocrine pulses
      that produce both NREM and rapid-eye-movement sleep. 5. Imposing a period of
      waking between drug administration and sleep onset may prove a generally useful
      strategy for determining whether a drug affects the homeostatic need for sleep or
      acutely stimulates sleep systems. This strategy can also help distinguish between
      toxic and physiological increases in delta EEG.

PMID- 8985870
TI  - Adrenoreceptor subtype mediating sympathetic-sensory coupling in injured sensory
      neurons.
AB  - 1. Teased axon recordings were made from 167 spontaneously active A beta- and A
      delta-afferents that ended in sciatic nerve end neuromas of 6-12 days standing.
      When challenged with a standard bolus of systemically applied adrenaline, 100
      (60%) responded, either with an increase in baseline firing frequency
      (excitation, 96/100) or with a decrease (suppression, 4/100). 2. Experiments
      using receptor type-selective antagonists indicated that the adreno-sensitivity
      was mediated by alpha 2 adrenoreceptors in 65% of the afferents sampled, by alpha
      1 adrenoreceptors in 13%, and about equally by alpha 1 and alpha 2
      adrenoreceptors in approximately 10%. In the remaining 13%, neither type of
      antagonist blocked adrenaline-evoked excitation, at least not at the doses used.
      Both excitatory and suppressive responses were primarily sensitive to alpha 2
      antagonists. 3. Experiments using receptor type-selective agonists substantiated
      the conclusion that sympathetic-sensory coupling at sites of nerve injury is
      mediated primarily by alpha 2 adrenoreceptors. 4. Recordings were also made from
      14 afferent neurons with spontaneous ectopic discharge originating in dorsal root
      ganglia (DRGs) L4 and L5. The rats had undergone transection of the ipsilateral
      sciatic nerve 8-93 days previously. All neurons responded to systemic adrenaline
      and/or trains of activity evoked in postganglionic sympathetic efferents with
      either excitation or suppression. As in the neuroma endings, responses in the
      large majority of cases were blocked by alpha 2-selective, but not by alpha 1
      selective adrenoreceptor antagonists. 5. The results indicate that sympathetic
      sensory coupling, both at nerve injury sites and in axotomized DRG neurons, is
      mediated primarily by alpha 2 adrenoreceptors. In a minority of afferent neurons,
      however, it appears to be mediated by alpha 1 adreno-receptors or by both alpha 1
      and alpha 2 adrenoreceptors. These functional results are consistent with
      receptor-type expression profiles from studies based on in situ hybridization and
      immunocytochemistry.

PMID- 8985871
TI  - Equivalence of amplified current flowing from dendrite to soma measured by
      alteration of repetitive firing and by voltage clamp in layer 5 pyramidal
      neurons.
AB  - 1. Plots of steady firing rate versus injected current (f-I relations) were
      constructed from intrasomatic injected current pulses applied alone (control
      relations) and together with dendritic glutamate iontophoresis (test relations)
      at sites on the distal apical dendrite 185-555 microns from the soma in layer 5
      pyramidal neurons from rat cortex studied in a brain slice. The test f-I
      relations exhibited a parallel shift along the current axis, and the slopes of
      the control and test relations differed by < 10% in most neurons. This behavior
      indicates that constant injected current and steady glutaminergic dendritic input
      evoke equivalent steady-state repetitive firing in a neuron with active
      dendrites. The parallel shift of the f-I curves allowed us to compute the
      amplitude of axial current arriving in the soma from the apical dendrite during
      repetitive firing. 2. We compared the transmitted current computed from the f-I
      curve shift with that measured by somatic voltage clamp during the same
      iontophoresis. When measured during voltage clamp at different somatic membrane
      potentials, the transmitted current increased with somatic depolarization (was
      amplified) in most cells, an observation inconsistent with passive dendrites.
      This larger-amplitude current closely predicted the transmitted current computed
      from the f-I curve shift, whereas the smaller transmitted current measured at
      resting potential did not. A set of control experiments indicated that these
      different predictions were well within the measurement error associated with
      computation of transmitted current based on f-I curve shifts. The action of
      blocking agents confirmed that the depolarizing amplification depended on
      tetrodotoxin (TTX)- and D-2-amino-5-phosphonopentoic acid (APV)-sensitive
      dendritic channels. 3. The agreement of two independent measurements (somatic
      voltage clamp and f-I curve shift) of the axial current transmitted from dendrite
      to soma indicates that the amplification of transmitted current observed in
      voltage clamp occurs physiologically. We discuss the usefulness of the effective
      current concept for determining synaptic weighting in network models of neurons
      with active dendrites.

PMID- 8985872
TI  - Effects of N- and L-type calcium channel antagonists on the responses of
      nociceptive spinal cord neurons to mechanical stimulation of the normal and the
      inflamed knee joint.
AB  - 1. The present study addresses the involvement of voltage-dependent calcium
      channels of the N and L type in the spinal processing of innocuous and noxious
      input from the knee joint, both under normal conditions and under inflammatory
      conditions in which spinal cord neurons become hyperexcitable. In 30 anesthetized
      rats, extracellular recordings were performed from single dorsal horn neurons in
      segments 1-4 of the lumbar spinal cord. All neurons had receptive fields in the
      ipsilateral knee joint. In 22 rats, an inflammation was induced in the
      ipsilateral knee joint by kaolin and carrageenan 4-16 h before the recordings.
      The antagonist at N-type calcium channels, omega-conotoxin GVIA (omega-CTx GVIA),
      was administered topically in solution to the dorsal surface of the spinal cord
      at the appropriate spinal segments in 6 rats with normal joints and in 12 rats
      with inflamed knee joints. The antagonist at L-type channels, nimodipine, was
      administered topically in 5 rats with normal joints and in 11 rats with inflamed
      knee joints. In another five rats with inflamed joints, antagonists at L-type
      calcium channels (diltiazem and nimodipine) and omega-CTx GVIA were administered
      ionophoretically with multibarrel electrodes close to the neurons recorded. 2.
      The topical administration of omega-CTx GVIA to the spinal cord reduced the
      responses to both innocuous and noxious pressure applied to the knee joint in a
      sample of 11 neurons with input from the normal joint and in a sample of 16
      neurons with input from the inflamed joint (hyperexcitable neurons). The
      responses were decreased to approximately 65% of the predrug values within
      administration times of 30 min. A similar reduction of the responses to innocuous
      and noxious pressure was observed when omega-CTx GVIA was administered
      ionophoretically to nine hyperexcitable neurons. In neurons with input from the
      normal or the inflamed knee joint, the administration of omega-CTx GVIA led also
      to a reduction of the responses to innocuous and noxious pressure applied to the
      noninflamed ankle joint. 3. The topical administration of nimodipine decreased
      the responses to innocuous and noxious pressure applied to the knee in a sample
      of 9 neurons with input from the normal joint and in a sample of 16 neurons with
      input from the inflamed knee joint (hyperexcitable neurons). Within
      administration times of 30 min, the responses were reduced to approximately 70%
      of the predrug values. In hyperexcitable neurons, the responses to innocuous and
      noxious pressure applied to the knee were also decreased during ionophoretic
      administration of nimodipine (6 neurons) and diltiazem (9 neurons). When the
      noninflamed ankle was stimulated, the responses to innocuous pressure were
      reduced neither in neurons with input from the normal knee nor in neurons with
      input from the inflamed knee, but the responses of hyperexcitable neurons to
      noxious pressure onto the ankle were reduced. The ionophoretic administration of
      the agonist at the L-type calcium channel, S(-)-Bay K 8644, enhanced the
      responses to mechanical stimulation of the knee joint in all 14 hyperexcitable
      neurons tested. The effect of S(-)-Bay K 8644 was counteracted by both diltiazem
      (in 6 of 6 neurons) and nimodipine (in 5 of 5 neurons). 4. These data show that
      antagonists at both the N- and the L-type voltage-dependent calcium channels
      influence the spinal processing of input from the knee joint. The data suggest,
      therefore, that voltage-dependent calcium calcium channels of both the N and the
      L type are important for the sensory functions of the spinal cord. They are
      involved in the spinal processing of nonnociceptive as well as nociceptive
      mechanosensory input from the joint, both under normal and inflammatory
      conditions. The present results show in particular that N- and L-type channels
      are likely to be involved in the generation of pain evoked by noxious mechanical
      stimulation in normal tissue as well as in the mechanical hyperalgesia that is
      usually pres

PMID- 8985873
TI  - Temporal processing of aortic nerve evoked activity in the nucleus of the
      solitary tract.
AB  - 1. Temporal processing of heterogenous afferent signals by nucleus of the
      solitary tract (NTS) neurons has been previously characterized. Experiments were
      performed in 26 pentobarbital-sodium-anesthetized male Sprague-Dawley rats to
      characterize the temporal processing of evoked activity in NTS neurons with the
      use of the aortic nerve, which contains exclusively arterial baroreceptor
      afferent fibers. 2. Extracellular single-cell activity was examined in the NTS
      during electrical stimulation of the aortic nerve with the use of a conditioning
      test paradigm. 3. Results were obtained from 49 neurons, 22 of which were
      characterized as receiving monosynaptic input from aortic nerve afferents. The
      average number of evoked potentials per aortic nerve stimulation was 1.1 +/- 0.1
      (SE) for the monosynaptic neurons and 1.2 +/- 0.2 for the polysynaptic neurons.
      Spontaneous activity averaged 3.7 +/- 0.7 Hz. No neuron exhibited an obvious
      pulse-rhythmic discharge. The average peak onset latency for monosynaptic cells
      of 17 +/- 2 ms (range 3-31 ms) was significantly (P < 0.05) shorter than the
      average of 26 +/- 1 ms (range 13-38 ms) for the polysynaptic cells. The average
      onset latency variability was also less in monosynaptic compared with
      polysynaptic cells (4 +/- 1 ms vs. 8 +/- 1 ms; P < 0.05). 4. Neurons
      characterized as receiving a monosynaptic input from the aortic afferents
      generally did not exhibit time-dependent inhibition. Significant inhibition was
      observed only at a conditioning-test interval of 50 ms, when the average test
      response was 79 +/- 8% of control. In contrast, the average response following a
      50-ms conditioning-test interval for neurons receiving polysynaptic input from
      the aortic nerve was only 32 +/- 8% of control. Significant inhibition was
      observed at conditioning-test intervals of up to 200 ms. 5. At a conditioning
      test interval of 50 ms, only 5 of 22 monosynaptic neurons were inhibited by >
      50%. Mean arterial pressure during the conditioning-test procedure was
      significantly lower for these neurons than for the 17 cells that were inhibited
      by < 50%. This suggests that the level of activity in convergent afferent input
      might influence the magnitude of time-dependent inhibition. 6. There was an
      essentially linear recovery from time-dependent inhibition evident in
      polysynaptic neurons that were tested at all conditioning-test intervals,
      suggesting a single mechanism of variable duration. Results reported here are
      consistent with current theory that time-dependent inhibition is mediated by
      disfacilitation. 7. The results demonstrate that NTS neurons receiving
      monosynaptic input from the aortic depressor nerve infrequently exhibit time
      dependent inhibition. This could allow for the original, unmodified afferent
      information to be dispersed to subsequent neurons. In contrast, neurons receiving
      polysynaptic input undergo time-dependent inhibition similar to that which has
      been reported for other afferent inputs. This could allow for differential
      degrees of fidelity in the transfer of the afferent information to specific
      efferent pathways. Therefore the temporal pattern of firing in individual
      baroreceptor afferents could play a critical role in the function of the arterial
      baroreflex and therefore in the regulation of blood pressure.

PMID- 8985874
TI  - Presynaptic depression of excitatory synaptic inputs to rat hypoglossal
      motoneurons by muscarinic M2 receptors.
AB  - 1. Whole cell recordings of glutamatergic excitatory postsynaptic currents
      (EPSCs) evoked by electrical stimulation in the reticular formation were made
      from visualized hypoglossal motoneurons (HMs) in rat brain stem slices. 2.
      Carbachol, muscarine, or physostigmine reduced EPSC amplitude to 50 +/- 3%, 37 +/
      3%, and 54 +/- 7% (mean +/- SE) of control, respectively; effects of carbachol
      and physostigmine were antagonized by atropine (1-2 microM). EPSC depression was
      most effectively antagonized by methoctramine, an M2 muscarinic acetylcholine
      receptor (mAChR) antagonist with a high affinity constant (pKB) of 8.07 for the
      receptor mediating this response, whereas pirenzepine, an M1 mAChR antagonist,
      had a pKB of < 7.0, showing that EPSC depression was mediated by the M2 mAChR. 3.
      Postsynaptic properties of HMs (holding current and input resistance), EPSCs
      (reversal potential, rise time, half-width, and decay time constant), and
      postsynaptic glutamate-gated currents (amplitude and waveform) were not altered
      by carbachol or muscarine. 4. Muscarine did not decrease presynaptic neuron
      excitability, because the frequency of spontaneous EPSCs in HMs in the absence of
      tetrodotoxin (TTX) was either unchanged or increased. Leak and action currents of
      reticular formation neurons were not significantly altered by muscarine. In
      contrast, with TTX present, the frequency of spontaneous miniature glutamatergic
      EPSCs in HMs was decreased by both carbachol (mean change = 203 +/- 46%) and
      muscarine (mean change = 185 +/- 26%), with no change in miniature EPSC amplitude
      distribution. 5. Muscarinic depression of excitatory transmission to HMs thus
      occurs at the presynaptic terminal, most probably affecting release mechanisms
      downstream from calcium entry, and is likely to be significant during rapid eye
      movement sleep, possibly underlying the loss of tongue tone and inspiratory
      activity during this state.

PMID- 8985875
TI  - Neural information transferred from the putamen to the globus pallidus during
      learned movement in the monkey.
AB  - 1. We studied the physiology of the neuronal projection from the striatum to the
      external and internal segments of the globus pallidus (GPe and GPi, respectively)
      in macaque monkeys. The objective of the study was to answer the following
      specific questions. 1) Which classes of the electrophysiologically identified
      striate neurons project to GPe and GPi? 2) What kind of information is
      transferred from the striatum to GPe and GPi during learned movement? 3) What are
      the physiological actions of striate projection neurons on target neurons in GPe
      and GPi? 4) What is the spatial pattern of the striatopallidal projections? 2.
      Sequential arm and orofacial movements were used as behavioral tasks. Visual
      stimuli triggered a sequence of three flexions-extensions of the elbow joint
      across the target, and the click of a solenoid valve triggered repetitive licking
      movements. 3. Striatopallidal projection neurons were electrophysiologically
      identified by antidromic activation after focal stimulation of either GPe or GPi.
      Of two classes of striate neurons, tonically active neurons (TANs) with tonic
      spontaneous discharges (2-8 imp/s) and broad action potentials, and phasically
      active neurons (PANs) with a very low spontaneous discharge rate (< 0.5 imp/ s)
      and high-frequency discharges in relation to behavioral tasks, PANs were
      identified as the projection neurons to either GPe or GPi. In 325 TANs examined
      by stimulation of GPe or GPi, no neuron was activated antidromically, even in the
      case of TANs located in the close vicinity of PANs that were identified as
      striatopallidal projection neurons. 4. The physiologically identified projection
      neurons (52 cells) in the striatum exhibited either discharges related to
      movement (30 cells) or discharges related to preparation for movement (4 cells)
      during performance of learned motor tasks. The activities of the remaining 17
      striatopallidal neurons either were not related to the behavioral tasks used or
      could not be characterized sufficiently in the tasks. However, all of the
      unidentified striatopallidal neurons were PANs, on the basis of the spontaneous
      discharge rate and the shape of the action potential. 5. PANs with movement
      related activity and those with preparation for movement-related activity were
      antidromically activated from the globus pallidus (GP). Not only the PANs that
      show burst discharges specifically at the beginning of a sequence of movement but
      also PANs that show phasic discharges time-locked to each movement of a sequence
      were identified as putaminopallidal projection neurons. On the other hand, no
      neurons that showed responses to sensory stimulus were identified as
      putaminopallidal neurons. 6. The conduction velocities of the putaminopallidal
      axons were estimated at approximately 1 m/s on the basis of the latency of
      antidromic activation and conduction distance. The PANs with activity only at the
      beginning of a sequential movement were more frequently found to project to GPi
      than to GPe, whereas the PANs with burst activity at each movement were more
      frequently found to project to GPe than to GPi. Among the GPi-projecting PANs,
      neurons with initial activity only showed a tendency to have longer latencies of
      activation from GPi than neurons with activity time-locked to each movement. 7.
      The physiological action of the striatopallidal projection was examined by
      switching from recording to microstimulation after identification of
      striatopallidal projection neurons in the putamen while recording evoked field
      potentials or spike discharges of single GP neurons located where the electrical
      stimulation evoked antidromic activation of the striate neurons with the lowest
      threshold. A small majority of GP neurons that exhibited increase of discharges
      during motor tasks received facilitatory putaminopallidal influences, whereas the
      vast majority of GP neurons that exhibited decrease of discharges during motor
      tasks received suppressive putaminopallidal influences.

PMID- 8985876
TI  - Neural encoding of shape: responses of cutaneous mechanoreceptors to a wavy
      surface stroked across the monkey fingerpad.
AB  - 1. The role of cutaneous mechanoreceptors in the tactile perception of shape was
      investigated. Objects whose surfaces were shaped as a pattern of smooth,
      alternating convex and concave cylindrical surfaces of differing radii of
      curvature were constructed such that there were no discontinuities in the slope
      of the surface. These "wavy surfaces" were stroked across the fingerpad of the
      anesthetized monkey and electrophysiological responses of slowly adapting type I
      mechanoreceptive afferents (SAs) and rapidly adapting type I mechanoreceptive
      afferents (RAs) were recorded. 2. For both SAs and RAs, each convexity indenting
      the skin evoked a burst of impulses and each concavity of the same curvature that
      followed elicited a pause in response. "Spatial event plots" (SEPs) of the
      occurrence of action potentials as a function of the location of the object on
      the receptive field were obtained and interpreted as the responses of a spatially
      distributed population of fibers. With increasing magnitude of curvature
      (equivalently, decreasing radius of curvature) of convexity, the mean width of
      the burst in the SEPs for each fiber type (representing the width of a region of
      skin containing active fibers) decreased and the mean discharge rate during the
      burst increased. Over a range of velocities of stroking from 1 to 40 mm/s, the
      number of RAs activated increased with velocity, whereas SAs were active at all
      velocities. For both SAs and RAs, the burst rates increased with velocity,
      whereas the widths of the bursts and pauses remained approximately invariant.
      Thus the spatial measures of burst or pause width provide a robust representation
      of the size of a feature on the object surface. 3. For a given velocity of
      stroking, the spatially distributed pattern of averaged discharge rates (spatial
      rate profile, SRP) provided a representation of the shape of the wavy surface.
      The distance between neighboring peaks in the SRP for individual RAs and SAs was
      approximately the same as the distance between the peaks of the wavy surface. The
      averaged SRP for a population of SAs provided a better representation of shape
      than that for RAs. Whereas active regions in the SEP can be isomorphic to the two
      dimensional form of the stimulus "footprint" in contact with the skin surface,
      the SRP, which in addition encodes the features of the stimulus in the third
      dimension normal to the skin surface, is not isomorphic to the stimulus shape. 4.
      When the sizes as well as the shapes of objects are varied, it is hypothesized
      that a central processing mechanism extracts the invariant property of shape from
      the slopes of the rising and falling phases of an SRP that has been normalized
      for overall differences in discharge rates. These differences would be expected
      to occur with variations in the parameters of stimulation such as compressional
      force, stroke trajectory, and stroke velocity. It was shown that a common feature
      of the mean SRP for SAs evoked by each wavy surface convexity, regardless of its
      radius, was the constancy of the slope from the base to the peak and from the
      peak to the base. Thus a possible code for the constant curvature of a cylinder
      is the constancy of the slopes along the rising and declining phases of the
      triangular-shaped spatial response profile evoked in the SA population by the
      cylindrical convexity.

PMID- 8985877
TI  - Differential involvement of group II and group III mGluRs as autoreceptors at
      lateral and medial perforant path synapses.
AB  - 1. Previous reports have shown that group III metabotropic glutamate receptors
      (mGluRs) serve as autoreceptors at the lateral perforant path, but to date there
      has been no rigorous determination of the roles of other mGluRs as autoreceptors
      at this synapse. Furthermore, it is not known which of the mGluR subtypes serve
      as autoreceptors at the medial perforant path synapse. With the use of whole cell
      patch-clamp and field excitatory postsynaptic potential (fEPSP) recording
      techniques, we examined the groups of mGluRs that act as autoreceptors at lateral
      and medial perforant path synapses in adult rat hippocampal slices. 2. Consistent
      with previous reports, the group III mGluR agonist (D,L)-2-amino-4
      phosphonobutyric acid reduced fEPSPs and excitatory postsynaptic currents (EPSCs)
      in the dentate gyrus. However, the group-II-selective agonist (2S,1'R,2'R,3'R)-2
      (2,3-dicarboxycyclopropyl)glycine (DCG-IV) also reduced fEPSPs and EPSCs,
      suggesting that multiple mGluR subtypes may serve as autoreceptors at perforant
      path synapses. 3. Selective activation of either medial or lateral perforant
      pathways revealed that micromolar concentrations of (L)-2-amino-4
      phosphonobutyric acid (L-AP4) reduce fEPSPs in lateral but not medial perforant
      path, suggesting group III involvement at the lateral perforant pathway.
      Conversely, DCG-IV and 2R, 4R-4-aminopyrrolidine-2,4-dicarboxylate, another group
      II-selective mGluR agonist, potently reduced fEPSPs at the medial but not lateral
      perforant path, suggesting that a group II mGluR may act as an autoreceptor at
      the medial perforant path-dentate gyrus synapse. 4. Antagonist studies with group
      selective antagonists such as (2S,3S,4S)-2-methyl-2-(carboxycyclpropyl)glycine
      (MCCG; group II) and alpha-methyl-L-AP4 (MAP4; group III) suggest differential
      involvement of each group at these synapses. The effect of L-AP4 at the lateral
      perforant path synapse was blocked by MAP-4, but not MCCG. In contrast, the
      effect of DCG-IV was blocked by application of MCCG, but not MAP4. 5. Previous
      studies suggest that the effect of L-AP4 at the lateral perforant path synapse is
      mediated by a presynaptic mechanism. In the present studies, we found that
      concentrations of DCG-IV that reduce transmission at the medial perforant path
      synapse reduce paired-pulse depression and do not reduce kainate-evoked currents
      recorded from dentate granule cells. This is consistent with the hypothesis that
      DCG-IV also acts by a presynaptic mechanism.

PMID- 8985878
TI  - Differential activation of two distinct mechanisms for presynaptic inhibition by
      a single inhibitory axon.
AB  - 1. Presynaptic inhibition of excitatory transmitter release evoked by inhibitory
      axon stimulation was studied at individual release boutons of the crayfish opener
      neuromuscular junction. 2. Presynaptic inhibition was maximal (approximately 30%)
      when a single inhibitory action potential preceded the excitatory test action
      potential by 1-2 ms. This inhibition lasted at most 5 ms. It was blocked by 50
      microM picrotoxin, and is probably mediated mainly by gamma-aminobutyric acid-A
      (GABAA) receptors. 3. Presynaptic inhibition produced by a brief train of
      inhibitory action potentials (5 pulses at 100 Hz) was maximal (approximately 60%)
      when the last inhibitory action potential (of the train) preceded the excitatory
      test action potential by 10 ms. This inhibition lasted up to 50 ms. It seems that
      in this case GABAB receptors were activated as well, because the combined action
      of picrotoxin (50 microM) and 20H-Saclofen (100 microM) was required to block the
      inhibition. 4. We thus show that one and the same inhibitory release bouton can
      differentially activate two distinct mechanisms for presynaptic inhibition by
      activating GABAA and GABAB receptors.

PMID- 8985879
TI  - Muscarine receptor activation in the substantia gelatinosa of the spinal
      trigeminal nucleus of the guinea pig.
AB  - 1. Intracellular recordings were made from slices of guinea pig spinal trigeminal
      nucleus pars caudalis (SG). 2. Muscarine [0.3-30 microM; half maximally effective
      concentration (EC50) = 2.9 microM] hyperpolarized 61% of SG neurons. The effect
      was mimicked by carbachol (0.3-30 microM; EC50 = 3.9 microM) and antagonized by
      pirenzepine (1 microM). Thirty-four percent of the neurons were depolarized by
      muscarine and carbachol (1-30 microM: EC50 = 5.7 microM), and the effect was
      antagonized by pirenzepine (100 nM). 3. In approximately 80% of recordings,
      muscarine (10-30 microM) evoked repetitive spontaneous inhibitory postsynaptic
      potentials (IPSPs) that were sensitive to bicuculline (10 microM). 4. Muscarine
      (1-30 microM; EC50 = 3 microM) decreased the amplitude of the majority of evoked
      excitatory postsynaptic potentials (EPSPs), and the effect was mimicked by
      carbachol and antagonized by pirenzepine (100 nM). 5. These results indicate that
      there are at least three mechanisms by which muscarine inhibits SG neurons: 1)
      hyperpolarization through activation of non-M1 receptors; 2) activation of gamma
      amino-butyric acid-containing interneurons that mediate IPSPs in a subset of
      neurons; and 3) a decrease in evoked EPSP amplitude. Muscarine can also activate
      SG neurons via interaction with an M1-type receptor.

PMID- 8985880
TI  - Variability of extracellular spike waveforms of cortical neurons.
AB  - 1. Here we study the variability in extracellular records of action potentials.
      Our work is motivated, in part, by the need to construct effective algorithms to
      classify single-unit waveforms from multiunit recordings. 2. We used microwire
      electrode pairs (stereotrodes) to record from primary somatosensory cortex of
      awake, behaving rat. Our data consist of continuous records of extracellular
      activity and segmented records of extracellular spikes. Spectral and principal
      component techniques are used to analyze mean single-unit wave-forms, the
      variability between different instances of a single-unit waveform, and the
      underlying background activity. 3. The spectrum of the variability between
      different instances of a single-unit waveforms is not white, and falls off above
      1 kHz with a frequency dependence of roughly f-2. This spectrum is different from
      that of the mean spike waveforms, which falls off roughly as f-4, but is
      essentially identical with the spectrum of background activity. The spatial
      coherence of the variability on the 10-micron scale also falls off at high
      frequencies. 4. The variability between different instances of a single-unit
      waveform is dominated by a relatively small number of principal components. As a
      consequence, there is a large anisotropy in the cluster of the spike waveforms.
      5. The background noise cannot be represented as a stationary Gaussian random
      process. In particular, we observed that the spectrum changes significantly
      between successive 20-ms intervals. Furthermore, the total power in the
      background activity exhibits larger fluctuations than is consistent with a
      stationary Gaussian random process. 6. Roughly half of the single-unit spike
      waveforms exhibit systematic changes as a function of the interspike interval.
      Although this results in a non-Gaussian distribution in the space of waveforms,
      the distribution can be modeled by a scalar function of the interspike interval.
      7. We use a set of 44 mean single-unit waveforms to define the space of
      differences between spike waveforms. This characterization, together with that of
      the background activity, is used to construct a filter that optimizes the
      detection of differences between single-unit waveforms. Further, an information
      theoretic measure is defined that characterizes the detectability.

PMID- 8985881
TI  - Activation of pharmacologically distinct metabotropic glutamate receptors
      depresses reticulospinal-evoked monosynaptic EPSPs in the lamprey spinal cord.
AB  - 1. Different metabotropic glutamate receptors (mGluRs) can modulate synaptic
      transmission in different regions in the CNS, but their roles at individual
      synaptic connections have not been detailed. We used paired intracellular
      recordings from reticulospinal axons and their postsynaptic target neurons in the
      lamprey spinal cord to investigate the effects of mGluR activation on
      glutamatergic synaptic transmission. 2. The mGluR agonists (1S,3R)-1
      aminocyclopentane-1,3-dicarboxyylic acid [(1S,3R)-ACPD] and L(+)-2-amino-4
      phosphonobutyric acid (L-AP4) both reduced the amplitude of monosynaptic
      excitatory postsynaptic potentials (EPSPs) elicited by stimulation of single
      reticulospinal axons. The depression of monosynaptic unitary EPSPs occurred
      without any apparent change in the input resistance of postsynaptic neurons.
      Furthermore, the mGluR agonists did not affect the amplitude of (RS)-alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarizations.
      Taken together, these results thus suggest that (1S,3R)-ACPD and L-AP4 depress
      reticulospinal synaptic transmission via presynaptic mechanisms. 3. (2S,1'S,2'S)
      2-(carboxycyclopropyl) glycine (L-CCG-I), which selectively activates group II
      mGluRs, also reduced the amplitude of reticulospinal-evoked EPSPs without any
      apparent change in the input resistance or membrane potential of the postsynaptic
      neuron. 4. The mGluR antagonist alpha-methyl-L-AP4 blocked the depression induced
      by L-AP4 but not that induced by (1S,3R)-ACPD. Furthermore, the effects of
      coapplication of (1S,3R)-ACPD and L-AP4 were additive, suggesting that they
      inhibit synaptic transmission by an action on pharmacologically distinct mGluRs.
      5. These results provide evidence for the colocalization of at least two
      different subtypes of presynaptic mGluRs on a single reticulospinal axon in the
      lamprey. These presynaptic mGluRs could serve as glutamatergic autoreceptors
      limiting the extent of reticulospinal-mediated excitation of spinal neurons.

PMID- 8985882
TI  - On bipolar cell responses in the teleost retina are generated by two distinct
      mechanisms.
AB  - 1. ON Bipolar cells were recorded in slices obtained from hybrid bass retinas.
      Cells were identified as bipolar cells by position in the slice, by
      characteristic voltage- and ligand-gated currents, and by filling with the
      fluorescent dye Lucifer yellow. Cells were recorded with the use of either whole
      cell or perforated-patch techniques. Standard electrophysiological protocols were
      used. Drugs were applied by puffing and by local superfusion. 2. Application of
      exogenous glutamate to ON bipolar cells generated two characteristic responses.
      One effect of glutamate was to open a conductance with a reversal potential close
      to the chloride equilibrium potential. The other effect of glutamate was to close
      a conductance with a reversal potential near 0 mV. These two effects of glutamate
      on ON bipolar cells match the effects of light described previously with the use
      of intracellular recordings. Thus the effects of glutamate that we report here
      appear to underlie the rod and cone inputs to these cells. 3. Many of the ON
      bipolar cells recorded demonstrated both classes of responses to glutamate. To
      isolate the two responses, 500 microM glutamate was first applied, and then
      glutamate in the presence of 5 microM 2-amino-4-phosphonobutyric acid (APB). APB
      specifically blocks the effects of glutamate on the putative roddriven glutamate
      receptor (the glutamate-elicited conductance decrease), allowing us to study in
      isolation the effects of glutamate on the cone component, the glutamate-activated
      chloride current (IGlu). 4. By isolating IGlu as described above, and taking
      advantage of the fact that amphotericin-perforated-patch recordings limit the
      diffusion of chloride ions between the patch pipette and the cell body, we found
      the physiological reversal potential of IGlu to be -58.9 +/- 7.7 (SD) mV. 5. Both
      the putative rod- and cone-mediated glutamatergic inputs to these bipolar cells
      could be activated by driving the photoreceptors with puffs of potassium. The
      currents recorded with this technique were very similar to those seen with direct
      application of glutamate.

PMID- 8985883
TI  - Mechanical response characteristics of the hearing organ in the low-frequency
      regions of the cochlea.
AB  - 1. With the use of an in vitro preparation of the guinea pig temporal bone, in
      which the apical turns of the cochlea are exposed, the mechanical and electrical
      responses of the cochlea in the low-frequency regions were studied during sound
      stimulation. 2. The mechanical characteristics were investigated in the fourth
      and third turns of the cochlea with the use of laser heterodyne interferometry,
      which allows the vibratory responses of both sensory and supporting cells to be
      recorded. The electrical responses, which can be maintained for several hours,
      were recorded only in the most apical turn. 3. In the most apical turn, the
      frequency locations and shapes of the mechanical and electrical responses were
      very similar. 4. The shapes of the tuning curves and the spatial locations of the
      frequency maxima in the temporal bone preparation compared very favorably with
      published results from in vivo recordings of hair cell receptor potentials and
      sound-induced vibrations of the Reissner's membrane. 5. Compressive
      nonlinearities were present in both the mechanical and the electrical responses
      at moderate sound pressure levels. 6. The mechanical tuning changed along the
      length of the cochlea, the center frequencies in the fourth and third turns being
      approximately 280 and 570 Hz, respectively. 7. The mechanical responses of
      sensory and supporting cells were almost identical in shape but differed
      significantly in amplitude radially across the reticular lamina.

PMID- 8985884
TI  - Response sensitivity and voltage gain of the rod- and cone-horizontal cell
      synapses in dark- and light-adapted tiger salamander retina.
AB  - 1. Rods, cones, and horizontal cells (HCs) were recorded in superfused, flat
      mounted isolated retinas of the larval tiger salamander, Ambystoma tigrinum,
      under dark- and light-adapted conditions. 2. Under dark-adapted conditions, HC
      responses to dim 500-nm light stimuli were mediated only by rods. In the linear
      voltage range (near the dark potentials), the average response to a light step of
      0.5 s (500 nm, 0.438 photons per micron2 per s) was 0.41 +/- 0.06 (SD) mV for
      rods and 1.86 +/- 0.52 mV for HCs. The step sensitivity of rods was approximately
      0.94 mV per photon micron2 s, or 0.032 mV per activated rhodopsin molecule (Rh*)
      rod second, and the step sensitivity of HCs was approximately 4.25 +/- 1.19 mV
      per photon micron2 s or 0.14 +/- 0.04 mV per Rh* rod second. The chord voltage
      gain of the rod-HC synapse had an average value of 4.54 and a range from 2.68 to
      7.32. 3. By the use of the spectral subtraction method, we found that the average
      cone-mediated HC response to a 750-nm light step that elicited an average cone
      response of 0.73 +/- 0.20 mV was 1.15 +/- 0.31 mV. The step sensitivity of cones
      under dark-adapted conditions was 0.0012 mV per photon micron2 s, and that of the
      cone-mediated-HC response was 0.0019 mV per photon micron2 s. The chord voltage
      gains of the cone-HC synapses under dark-adapted conditions had an average value
      of 1.58 and a range from 0.82 to 2.05. 4. Under light-adapted conditions (with a
      500-nm/-2.40 background light, which desensitized rod responses but did not
      substantially reduce the cone responses), the cones had an average response to a
      light step of 0.5 s (500 nm/-3.3) of 0.78 +/- 0.09 mV, and this response did not
      vary with time. The HC response to the same light step had an average value of
      3.95 +/- 3.41 mV 3 min after the background light onset, and it increased with
      time until reaching a steady-state value of 5.95 +/- 3.63 mV approximately 15 min
      after the background light onset. The average chord voltage gain of the cone-HC
      synapse under such light-adapted conditions was 5.06 at 3 min after background
      light onset and 7.63 at 15 min after background light onset. These values are
      approximately 3-5 times higher than the chord voltage gain of the cone-HC synapse
      under dark-adapted conditions. 5. The background-induced increase of the chord
      voltage gain of the cone-HC synapse suggests that similarly to the rod-HC
      synapse, the voltage gain of the cone-HC synapse in the tiger salamander retina
      can also be modulated by light. Additionally, our results suggest that certain
      time-dependent process(es) in the synaptic cleft or postsynaptic membrane may be
      responsible for such modulation. 6. In addition to determining the average values
      of response sensitivity and chord voltage gains of the rod- and cone-HC synapses,
      we studied the variation of these parameters among different HCs. HCs with higher
      rod-HC synaptic gain had lower cone-HC synaptic gain, and HCs with lower rod-HC
      synaptic gain exhibited higher cone-HC synaptic gain under both dark- and light
      adapted conditions. This suggests that the rod-HC and cone-HC synaptic gains in
      HCs are complementary to each other, and voltage responses of all HCs under dark-
      or light-adapted conditions are of comparable amplitudes.

PMID- 8985885
TI  - Maturation in properties of motoneurons and their segmental input in the neonatal
      rat.
AB  - 1. The isolated neonatal rat spinal chord preparation was used to investigate the
      development of segmental afferent input to lumbar motoneourons during the first
      nine postnatal days. Motoneurons, identified with the use of antidromic
      stimulation of the ventral roots, were characterized electrophysiologically, and
      their synaptic input in response to stimulation of the homologous dorsal root was
      studied. 2. Motoneurons in postnatal day (P) 1-3 preparations exhibited lower
      rheobase and lower input conductance than those impaled in spinal cords taken
      from animals at P7-9. This finding is consistent with the increase in motoneuron
      size known to occur during this time. 3. Monosynaptic excitatory postsynaptic
      potentials (EPSPs) evoked at low-frequency (0.1-Hz) stimulation in high-Ca2+
      saline exhibited no change in mean amplitude between P1-3 and P7-9 despite an
      increase in input conductance of the motoneurons, suggesting that some aspect of
      these synapses underwent a compensatory change. Polysynaptic EPSPs were smaller
      in the older animals. 4. When bursts of stimuli were delivered at higher
      frequencies ranging from 10 to 167 Hz, the EPSPs exhibited substantial
      depression. The depression of monosynaptic EPSPs was significantly less at P7-9
      than at P1-3. Changing the bathing solution from a high-Ca2+ saline to a low
      Ca2+/high-Mg2+ saline reduced the amplitude of the monosynaptic EPSP and made it
      less susceptible to depression during high-frequency stimulation. Facilitation of
      the evoked response, which has been observed in the adult rat, was never seen
      under any of these conditions. 5. Although synapses on high-rheobase motoneurons
      exhibited less depression than those on low-rheobase motoneurons, as anticipated
      from previous results in adults, the EPSPs at synapses on high-rheobase
      motoneurons tended to be larger in amplitude, not smaller as expected. This
      suggests that the specialization among synapses on motoneurons that exists in
      adults has not yet developed by P7-9. Instead, EPSP amplitude may be greater in
      motoneurons that have been growing rapidly, such as the high-rheobase motoneurons
      found during these stages of development. 6. Evidence is presented that the
      growing diversity shown in modulation behavior at the Ia afferent motoneuron
      synapse during the first postnatal week is determined primarily by motoneuron
      characteristics. It is speculated that as motoneurons grow during the immediate
      postnatal period, the presynaptic terminal regions of axons terminating on them
      become specialized to render the synapse less susceptible to depression. This
      specialization may be myelination of the afferent terminals or may perhaps be
      related to the transmitter release process itself. The adult distribution of
      depression develops later, presumably as the components of the monosynaptic
      reflex mature.

PMID- 8985886
TI  - Ionic basis of the postsynaptic depolarizing GABA response in hippocampal
      pyramidal cells.
AB  - 1. Whole cell voltage-clamp recording with recording pipette solutions of
      differing ionic composition was used to determine the ionic basis of the
      depolarizing gamma-aminobutyric acid (GABA) response. In the presence of 4
      aminopyridine and excitatory amino acid receptor blockers, giant GABA-mediated
      postsynaptic currents (GPSCs) were recorded from CA3 pyramidal neurons in
      hippocampal slices from adult guinea pigs. With the GABAB component blocked, the
      GPSC was composed of an initial outward current (GABAA component) that peaked at
      115 ms followed by a late inward current (GABAD component) that peaked at 400-600
      ms. 2. Reduction of the intracellular concentration of potassium ([K+]i)resulted
      in no significant change in the reversal potential of the GABAD component of the
      GPSC, indicating that it is not a nonspecific cation current. 3. The HCO3-
      permeability of the channel mediating the GABAD response was assessed by using
      recording pipette solutions containing three different concentrations of
      bicarbonate ([HCO3-], 19, 49, and 102 mM). The reversal potential of the GABAD
      response shifted in the depolarizing direction as the HCO3- equilibrium potential
      was shifted in the depolarizing direction, indicating that the channel mediating
      the GABAD response is permeable to HCO3-. The reversal potential of the GABAD
      response was more sensitive to changes in recording pipette [HCO3-] than the
      reversal potential of the GABAA response, indicating that the GABAD response is
      carried by HCO3- to a greater extent than the GABAA response. 4. The outward
      current-inward current sequence of the biphasic GPSC was reversed to an inward
      current-outward current sequence by using a high [Cl-]/low [HCO3-] recording
      pipette solution (40 mM Cl-/6 mM HCO3-), indicating that the GABAA component is
      more sensitive to changes in [Cl-]i, and the GABAD component is more sensitive to
      changes in [HCO3-]i. 5. These data indicate that the GABAD component of the GPSC
      is predominantly carried by HCO3-. While this result supports the recently
      propsed chloride accumulation model, the model in its present form cannot explain
      the inward current-outward current polarity sequence of the GPSC recorded with
      the high [Cl-]/low [HCO3-] intracellular solution. The data obtained using that
      solution reveal the need for a more expansive chloride accumulation/ depletion
      model or for a model utilizing two distinct ionotropic GABA channels with
      different anion permeability ratios to account for the biphasic nature of the
      GPSC.

PMID- 8985887
TI  - Differential responses of Aplysia siphon motor neurons and interneurons to tail
      and mantle stimuli: implications for behavioral response specificity.
AB  - 1. Tail shock and mantle shock elicit different forms of siphon responses in
      Aplysia (flaring and backward bending vs. constriction and forward bending,
      respectively). Moreover, training with these two unconditioned stimuli (USs) in
      US-alone or classical conditioning paradigms differentially modifies the
      direction of the response to a siphon tap subsequently presented. As a first step
      toward addressing neural mechanisms underlying this response specificity, we
      systematically mapped the central siphon withdrawal circuit to determine which
      motor neurons and interneurons are differentially engaged by, and potentially
      modified by, tail and mantle USs. We utilized semi-intact preparations consisting
      of the intact mantle organs (including the gill and siphon), the tail, and the
      abdominal and circumesophageal ganglia. USs were delivered either cutaneously
      through silver wires implanted in the tail and mantle or via suction electrodes
      to the tail and branchial nerves. 2. We found that one class of central siphon
      motor neurons, the LFSB cells, was preferentially activated by tail USs, whereas
      other siphon motor neurons, the LBs cells and RDs cells, were preferentially
      activated by mantle USs. These motor neurons thus appear to be the final common
      path for the differential siphon movements to these USs. In addition, because
      activation of these cells can elicit neuromuscular facilitation and thereby
      enhance siphon movements, this differential activation may contribute to
      behavioral response specificity by imposing a specific response bias. 3. L29
      interneurons, which both mediate and modulate the siphon withdrawal response,
      responded preferentially and exhibited synaptic facilitation selectively in
      response to tail shock USs. In contrast, L34 and the interneuron II network did
      not show differential activation. Facilitation at L29-LFSB connections following
      training with tail shock may contribute to tail-directed siphon responses to
      siphon tap and may thus be an additional mechanism contributing to behavioral
      response specificity. Possibly, facilitation at other L29 connections could also
      enhance its modulatory capabilities. 4. The generation of specific response
      topographies thus appears to involve the coordinate regulation of diverse
      neuronal elements and multiple mechanisms, which may contribute to different
      aspects of learning.

PMID- 8985888
TI  - Presynaptic A1 inhibitory/A2A facilitatory adenosine receptor activation balance
      depends on motor nerve stimulation paradigm at the rat hemidiaphragm.
AB  - 1. Adenosine modulates acetylcholine (ACh) release from the rat motor nerve
      terminals. Tonic activation of presynaptic A1 inhibitory and/or A2A facilitatory
      adenosine receptors is regulated by the concentration of the nucleoside at the
      synapse. The parameters (frequency, duration of pulses, train length) of nerve
      stimulation determine the amount of transmitter and/or modulator released, and
      have long been proposed as important features of synaptic control. This prompted
      us to investigate which was the prevailing response to adenosine on evoked [3H]
      ACh release from rat phrenic nerve hemidiaphragm preparations in different
      stimulation conditions. 2. With low-frequency, short-duration pulses (5 Hz, 40
      microseconds in duration), the adenosine inhibitory tonus (approximately 30%)
      predominates. The magnitude of the adenosine tonic inhibition was dependent on
      the number of pulses (250-750) delivered in each stimulation train, e.g., the
      facilitatory effect of adenosine deaminase (ADA, 0.5 U/ml) and the inhibitory
      effect of the adenosine uptake blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI, 5
      microM) reached significance only when > 250 pulses were applied. Facilitation
      was only observed with high concentrations of either exogenous adenosine (> 100
      microM) or NBTI (> 10 microM). 3. When the stimulation pulse duration was
      increased to 1 ms (5 Hz, 750 pulses), endogenously generated adenosine
      consistently facilitated evoked [3H]-ACh release. In these conditions, ADA (0.5
      U/ml) decreased evoked [3H]-ACh release by 29 +/- 4% (mean +/- SE) (n = 3), and
      both NBTI (3-30 microM) and adenosine (10-500 microM), which had biphasic effects
      with pulses of 40 microseconds, facilitated transmitter release. 4. When high
      frequency "trains" (50 Hz, 40 microseconds, 500 pulses) were applied, both ADA
      (0.5 U/ml) and NBTI (5 microM) failed to modify evoked [3H]-ACh release. To
      bypass putative feedforward inhibition of ecto-5'-nucleotidase induced by
      released ATP, which might reduce adenosine formation during high-frequency
      trains, experiments containing a series of five high-frequency "bursts" (50 Hz,
      40 microseconds, 100 pulses) with variable interburst intervals (5-20 s) were
      performed. In such conditions, the prevailing tonic response to adenosine turned
      out to be facilitatory, because ADA (0.5 U/ml) inhibited and NBTI (5 microM)
      facilitated evoked [3H]-ACh release. The magnitude of the inhibitory effect of
      ADA (0.5 U/ml) ranged from -9 +/- 6% (n = 4) to -54 +/- 8% (n = 5) as the
      interburst interval changed from 5 to 20 s, respectively. 5. Prolongation of
      individual pulses from 40 microseconds to 1 ms (5 Hz frequency) or increasing the
      frequency of stimulation (1-50 Hz, 40 microseconds) did not significantly change
      the excitatory effect of the A2A receptor agonist 2-[4-(2-p
      carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680C). In
      contrast, the inhibitory effect of the A1 receptor agonist R-N6
      phenylisopropyladenosine was significantly attenuated in both stimulation
      conditions. 6. In conclusion, the results suggest that high-intensity, high
      frequency motor nerve stimulation critically influences endogenous adenosine
      formation and the A1/A2A receptor activation balance, i.e., it potentiates the
      tonic adenosine A2A-receptor-mediated facilitation of ACh release, whereas
      activation of the inhibitory A1 receptors becomes less effective. A model is
      proposed that attempts to further elucidate adenosine's involvement in synaptic
      transmission adaptation.

PMID- 8985889
TI  - Functional changes in sodium conductances in the human neuroblastoma cell line SH
      SY5Y during in vitro differentiation.
AB  - 1. The electrophysiological properties of voltage-dependent sodium currents were
      studied in the human neuroblastoma cell line SH-SY5Y before and after in vitro
      differentiation with retinoic acid, with the use of the whole cell variant of the
      patch-clamp technique. 2. Voltage steps from a holding level of -90 mV to
      depolarizing potentials elicited, in both undifferentiated and differentiated
      cells, fast inward sodium currents that were full inactivating and tetrodotoxin
      sensitive. 3. In undifferentiated cells the current peaked at -10 mV, the half
      activation potential was -35 mV, and the half-inactivation potential was -81 mV.
      In differentiated cells the current peaked at + 10 mV, the half-activation
      potential was -28 mV, and the half-inactivation potential was -56 mV. Moreover,
      the peak current amplitude was about a factor of 2 larger and inactivation
      kinetics was about a factor of 2 slower than in undifferentiated cells. 4. This
      diversity in sodium channel properties was related to differences in cell
      excitability. Under current-clamp conditions, intracellular injection of
      rectangular depolarizing current stimuli from a hyperpolarized membrane potential
      of about -100 mV elicited graded and weak regenerative responses in
      undifferentiated cells, whereas overshooting action potentials with faster rising
      phases could be elicited in differentiated cells.

PMID- 8985890
TI  - Greater residual vision in monkeys after striate cortex damage in infancy.
AB  - 1. Monkeys with large unilateral surgical ablations of striate cortex, sustained
      either in adulthood or at 5-6 wk of age, were trained on an oculomotor detection
      and localization task and tested with visual stimuli in the hemifields
      ipsilateral and contralateral to the lesion 2-5 yr after surgery. 2. Monkeys with
      lesions sustained in adulthood were largely unable to detect stimuli in the
      hemifield contralateral to the lesion, with only one monkey showing recovery
      toward the end of testing. Monkeys with lesions of striate cortex made in
      infancy, however, each showed residual detection capacity at the beginning of
      testing and improved to near normal by the end of testing. 3. Each of the monkeys
      showing a residual ability to detect within the contralateral hemifield was also
      able to localize visual targets with eye movements. 4. These findings demonstrate
      that the vision surviving striate cortex damage in primates is more robust after
      early damage as has been shown to be the case for primary somatosensory, motor,
      and association cortex.

PMID- 8985891
TI  - Dopamine enhancement and depression of glutamate-regulated calcium and electrical
      activity in hypothalamic neurons.
AB  - 1. The neurotransmitter dopamine is found throughout the hypothalamus both in
      cell bodies and in axons originating from intra- and extrahypothalamic sources.
      To study the mechanisms of action of dopamine on cultured rat hypothalamic
      neurons, particularly in relation to Ca2+ regulation, we used Ca2+ digital
      imaging with fura-2 and whole cell patch-clamp recording. We focused on the
      modulatory actions of dopamine on glutamate. 2. Dopamine administration had
      little or no independent effect on intracellular Ca2+. However, in the presence
      of tetrodotoxin to block action potentials and action-potential-dependent
      transmitter release, dopamine (10 microM for 2-3 min) caused an increase in
      glutamate-evoked Ca2+ rises in 22% of 64 neurons and depressed glutamate-evoked
      Ca2+ rises in an equal number of neurons. Shorter exposure to dopamine reduced
      the number of responding cells. 3. Dopamine application to neurons with an
      elevated Ca2+ due to synaptic release of glutamate (in the absence of
      tetrodotoxin) generally caused a decrease in Ca2+ levels (40% of 106 neurons),
      but sometimes increased cytosolic Ca2+ (10% of 106 neurons). That dopamine
      influenced cells differently in conditions of spontaneous activity compared with
      evoked activity may be due to dopamine effects on presynaptic receptors detected
      under conditions of ongoing synaptic release of glutamate. 4. Dopamine modulation
      of glutamate responses was detected at early stages of neuronal development
      (embryonic day 18 after 2 days in vitro) and also after 60 days in vitro. 5. The
      D1, D2, and D3 dopamine receptor agonists SKF38393, quinpirole, and 7-OH-DPAT (+/
      7 hydroxy-dipropylaminotetralin) caused a reduction in Ca2+ levels raised by
      endogenous glutamate release or evoked by exogenous glutamate application. 6. To
      block the actions of dopamine released by hypothalamic neurons, D1 and D2
      dopamine receptor antagonists were used. As with dopamine, dopamine antagonists
      had no effect on intracellular Ca2+ during glutamate receptor blockade. In the
      absence of glutamate receptor block, the D1 antagonist SCH23390 (1 microM)
      reduced Ca2+ in responding cells; in contrast, the D2 antagonist eticlopride (1
      microM) generated a delayed increase in Ca2+ levels. 7. Dopamine is known to
      activate second messengers through G proteins independent of changes in membrane
      potential or input resistance. Whole cell recording was used to demonstrate that,
      parallel to the modulation of Ca2+, dopamine exerted a dramatic change in
      glutamate-mediated electrical activity, generally depressing activity and
      hyperpolarizing the membrane potential (8 of 15 neurons). In a smaller number of
      neurons (5 of 15), dopamine enhanced glutamate-mediated excitatory activity. 8.
      Dopamine-evoked changes in membrane potential were in part mediated through
      modulation of glutamate actions. Dopamine depressed glutamate-evoked currents in
      a dose-dependent fashion, with Hill slopes in individual neurons ranging from 0.3
      to 0.6. Dopamine could also evoke a direct hyperpolarizing action on hypothalamic
      neurons in the presence of tetrodotoxin or glutamate receptor blockers, at least
      in part by opening K+ channels. 9. Glutamate plays an important role as a primary
      excitatory transmitter within the hypothalamus. Our data support the hypothesis
      that a major mechanism of dopamine's influence on hypothalamic neurons involves
      the modulation of glutamate's excitatory action, mostly by inhibition. This is
      consistent with the hypothesis that modulation of glutamate activity may be an
      important mechanism of dopamine action throughout the nervous system.

PMID- 8985892
TI  - Oscillatory activity in sensorimotor cortex of awake monkeys: synchronization of
      local field potentials and relation to behavior.
AB  - 1. Oscillations of 20-40 Hz were observed in local field potentials (LFPs) and
      unit activity in sensorimotor cortices of three awake monkeys while the monkeys
      performed trained wrist movements and untrained exploratory arm movements. The
      mean frequency of LFP oscillations was 25.9 +/- 1.4 (SD) Hz and the number of
      cycles of oscillations per episode was variable, with a mean of 4.2 +/- 0.5 (mean
      +/- SE). 2. Oscillatory episodes occurred most often when the monkeys retrieved
      raisins from a Kluver board (0.59 +/- 0.23 episodes per s, mean +/- SD) or from
      unseen locations with the use of somatosensory feedback (0.62 +/- 0.12 episodes
      per s); they occurred less often when the monkeys performed repetitive wrist
      flexion and extension movements (0.22 +/- 0.04 episodes per s) or sat quietly at
      rest (0.23 +/- 0.17 episodes per s). 3. The amplitude of LFP oscillations
      increased with depth in cortex, reaching a maximum between 1 and 2 mm. LFP
      oscillations at the surface of the cortex were 180 degrees out of phase with
      oscillations in the deep cortical layers. The phase shift (with respect to the
      deep layers) decreased with depth in the cortex and disappeared at depths of > 1
      mm. 4. LFPs were recorded simultaneously at multiple sites in the sensorimotor
      cortex when monkeys retrieved raisins from a Kluver board or from unseen
      locations. Cross-correlation of LFPs recorded at different sites indicated that
      oscillations in the 20- to 40-Hz range could become synchronized at sites
      separated by up to > or = 14 mm in the precentral cortex. 5. The probability of
      occurrence of significant correlations between LFP oscillations at paired sites
      and the average correlation amplitude decreased with increasing horizontal
      separation of sites in precentral cortex. The phase shift between LFP
      oscillations recorded at paired sites did not change significantly with
      increasing horizontal separation. 6. For paired sites in precentral cortex, the
      average strength of correlations and the proportion of oscillations that were
      significantly correlated were greater during exploratory behaviors such as
      retrieving raisins from slots of the Kluver board than during periods of rest or
      overtrained wrist movements. 7. Oscillations could become synchronized with small
      phase shifts (0.5 +/- 1.6 ms) between pre- and postcentral cortical sites.
      Average strength and probability of occurrence of significant correlations
      between pre- and postcentral LFPs increased during exploratory behaviors. 8.
      Oscillations occurred simultaneously in the left and right motor cortex and could
      become synchronized with negligible phase shifts when the monkey performed
      bimanual manipulations. However, synchronization occurred as often and as
      strongly for unimanual as for bimanual manipulations. 9. These results indicate
      that episodes of 20- to 40-Hz oscillations occur often and become synchronized
      over a large cortical area during exploratory forelimb movements. However, they
      have no reliable relation to particular components of the movement and therefore
      seem unlikely to be involved directly in movement execution; instead, they may
      represent a neural correlate of attention during demanding sensorimotor
      behaviors.

PMID- 8985893
TI  - Synchronization of neurons during local field potential oscillations in
      sensorimotor cortex of awake monkeys.
AB  - 1. The neural activity associated with 20- to 40-Hz oscillations in sensorimotor
      cortex of awake monkeys was investigated by recording action potentials of single
      and multiple units. At a given site, activity of many units became synchronized
      with local field potential (LFP) oscillations. Cycle-triggered histograms (CTHs)
      of unit spikes aligned on cycles of LFP oscillations indicated that about two
      thirds of the recorded units (n = 268) were entrained with LFP oscillations. On
      average, units had the highest probability of spiking 2.7 ms before peak LFP
      negativity, corresponding to a -27.6 degrees phase shift relative to the negative
      peak of the LFP. 2. The average relative modulation amplitude (RMA), defined as
      the ratio of amplitude of oscillatory component of CTH and the baseline
      multiplied by 100, was 45 +/- 27% (mean +/- SD). The RMAs of single units did not
      differ significantly from those of multiple units. 3. Phase shifts and RMAs did
      not vary systematically with the cortical depth of recorded units. 4.
      Autocorrelation histograms (ACHs) of entrained units exhibited clear 20- to 40-Hz
      periodicity if they were compiled with spikes that occurred during oscillatory
      episodes in LFPs. ACHs of spikes outside oscillatory episodes usually did not
      show periodicity. Global ACHs of all spikes typically showed weak or no evidence
      of periodic activity. 5. Cross-correlation histograms (CCHs) between pairs of
      units complied with all spikes, whether they occurred during or outside LFP
      oscillations, seldom revealed significant features (19 of 134 pairs or 14%).
      However, CCHs compiled with spikes that occurred during oscillatory episodes (OS
      CCHs) had significant features in 67 of 134 pairs recorded ipsilaterally; in
      these 67 cases, units at both sites showed modulation in CTHs. 6. The latencies
      of the OS-CCH peaks (taking the medial unit as reference) were normally
      distributed about a mean of -0.5 +/- 13 ms. Normalized peak height of CCHs
      (peak/baseline x 100) was, on average, 14.3 +/- 11.2%. Peak latency and
      normalized peak amplitude did not change significantly with horizontal separation
      of recorded precentral pairs up to 14 mm. 7. Units in the left and right
      hemispheres could become synchronized during oscillations. Significant features
      in OS-CCH were detected in 22 of 42 pairs of units recorded bilaterally. The
      average peak latency was 0.2 +/- 8.0 ms and the average normalized peak amplitude
      was 10 +/- 8%. These parameters did not differ significantly from those for
      ipsilateral OS-CCHs. 8. Oscillations tended to affect both the temporal structure
      and net rate of unit firing. For each unit, the firing rate was clamped to a
      narrow range of frequencies during oscillatory episodes. The coefficient of
      variation (SD/mean) of firing rates was significantly reduced during oscillatory
      episodes compared with prior rates (P < 0.001, paired t-test). However, the
      overall mean firing rate of each unit during all oscillatory episodes did not
      differ from its average rate immediately before the episodes. Thus oscillatory
      episodes tended to clamp mean firing rates to the cells' average rates outside
      episodes. 9. The strength of synchronization between units during oscillatory
      episodes was unrelated to their involvement in the task. For pairs of precentral
      units recorded ipsilaterally, the probability of occurrence of significant
      features in the OS-CCH was slightly larger when both units of the pair were task
      related (33 of 56 pairs or 59%) than when only one unit was task related (20 of
      39 pairs or 51%) or neither unit was task related (7 of 16 or 44%). However,
      these differences were not statistically significant. The magnitude of the
      correlation peak and the latency to peak were also not significantly different
      for the three cases. 10. These results suggest that units across wide regions can
      become transiently synchronized specifically during LFP oscillations, even if
      their spikes are uncorrelated during nonoscillatory periods.

PMID- 8985894
TI  - Different mechanisms regulate IPSC kinetics in early postnatal and juvenile
      hippocampal granule cells.
AB  - 1. Monosynaptic inhibitory postsynaptic currents (IPSCs) were recorded from early
      postnatal and juvenile dentate granule cells in rat brain slices at room
      temperature. The focally evoked currents were mediated by gamma-aminobutyric acid
      A (GABAA) receptors. 2. IPSCs were characterized by a steep rising phase and a
      slower, monoexponential decay time course. The decay time constant was potential
      dependent and average values ranged from 33 ms at a holding potential of -60 mV
      to 58 ms at a holding potential of +40 mV. 3. IPSCs were studied in tissue from
      animals between postnatal day (p) 3 and p25. All kinetic parameters as well as
      the mean current amplitude were unchanged during this ontogenetic period. 4. In
      juvenile granule cells from animals aged 13-16 days, addition of the GABA uptake
      blocker (R)-N-[4,4-bis (3-methyl-2-thienyl) but-3-en1-yl] nipecotic acid
      (tiagabine) (10 microM) prolonged the decaying phase of the IPSCs. The current
      decay remained monoexponential but the time constant increased to 250% of control
      values. Mean current amplitudes remained largely unchanged. 5. In contrast,
      tiagabine had no effect on IPSCs in early postnatal tissue. The decay time
      constant remained unchanged in cells recorded from animals aged p4-p6. Other
      uptake blockers were also ineffective during the first postnatal week, whereas
      beta-alanine, NNC-711, and L-2,3-diaminoproprionic acid enhanced the decay time
      constant in the older tissue (p13-p16). 6. Hypoosmolaric extracellular solution
      was applied to restrict the extracellular space. In juvenile tissue (p13-p16),
      IPSCs were not affected by this treatment, whereas early postnatal granule cells
      (p4-p6) displayed clearly prolonged IPSC decay time constants (165% of control).
      7. We conclude that the mechanism governing the kinetics of evoked IPSCs in
      granule cells changes during ontogenesis. Whereas in early postnatal tissue the
      transmitter leaves the postsynaptic site by diffusion, GABA uptake becomes time
      limiting after 2 wk of postnatal development.

PMID- 8985895
TI  - Loop gain of reflexes controlling human standing measured with the use of
      postural and vestibular disturbances.
AB  - 1. In this study we measured the loop gain of postural reflexes in standing human
      subjects. Reflex activity is conventionally described in terms of the muscle
      activation arising from a perturbation, but in this study the ability of the
      evoked muscle activity to correct the perturbation was also measured, and the
      behavior of the entire feedback loop is described. 2. A weak continuous random
      perturbation was applied at waist level to standing subjects. The effects of the
      perturbation on body sway and soleus electromyogram (EMG) were identified by
      cross-correlation, and spectral analysis was used to estimate the open-loop
      reflex transmission characteristics (i.e., sway to EMG). Under the same
      conditions, activity in the leg muscles was evoked by galvanic vestibular
      stimulation with the use of a continuous randomly varying current. The effects on
      soleus EMG and the subsequent body sway were identified by cross-correlation.
      This allowed calculation of the open-loop muscle and load behavior (i.e., EMG to
      sway). From these open-loop reflex and muscle and load transfer functions, the
      loop gain and phase were calculated. 3. In addition to the gain of the feedback
      loop, the study describes the transmission characteristics of reflex responses in
      the leg muscles associated with body sway and the effects of excluding visual and
      proprioceptive contributions to the response; the transfer function of human
      soleus with a stimulus that preserves the normal recruitment of motoneurons,
      including the effects of different load conditions on the muscle; and the
      transmission characteristics of vestibular pathways that evoke responses in the
      leg muscles during standing in situations that might modify the reflexes. 4. When
      standing, the loop gain of reflex feedback is approximately unity and is
      unchanged by eye closure and stability of support. Reflex transmission introduced
      a marked phase advance, and this served to offset most of the phase lag
      introduced by muscle and load. The residual phase lag could explain the frequency
      of tremor observed during standing (6-8 Hz). 5. The gain of the feedback loop
      (approximately 1) is higher than suggested by both previous estimates and
      theoretical considerations, but is still insufficient to explain the stability of
      normal human standing. This implies that, although sensory information is used to
      control posture, it does not do so exclusively through a negative feedback
      control process. The experimental findings are consistent with a reflex response
      based on a feed-forward process, and this would result in prediction of the
      response necessary to counteract a postural disturbance.

PMID- 8985896
TI  - Three-dimensional vector analysis of the human vestibuloocular reflex in response
      to high-acceleration head rotations. I. Responses in normal subjects.
AB  - 1. The kinematics of the human angular vestibuloocular reflex (VOR) in three
      dimensions was investigated in 12 normal subjects during high-acceleration head
      rotations (head "impulses"). A head impulse is a passive, unpredictable, high
      acceleration (3,000-4,000 degrees/s2) head rotation of approximately 10-20
      degrees in roll, pitch, or yaw, delivered with the subject in the upright
      position and focusing on a fixation target. Head and eye rotations were measured
      with dual search coils and expressed as rotation vectors. The first of these two
      papers describes a vector analysis of the three-dimensional input-output
      kinematics of the VOR as two indexes in the time domain: magnitude and direction.
      2. Magnitude is expressed as speed gain (G) and direction as misalignment angle
      (delta). G is defined as the ratio of eye velocity magnitude (eye speed) to head
      velocity magnitude (head speed). delta is defined as the instantaneous angle by
      which the eye rotation axis deviates from perfect alignment with the head
      rotation axis in three dimensions. When the eye rotation axis aligns perfectly
      with the head rotation axis and when eye velocity is in a direction opposite to
      head velocity, delta = 0. The orientation of misalignment between the head and
      the eye rotation axes is characterized by two spatial misalignment angles, which
      are the projections of delta onto two orthogonal coordinate planes that intersect
      at the head rotation axis. 3. Time series of G were calculated for head impulses
      in roll, pitch, and yaw. At 80 ms after the onset of an impulse (i.e., near peak
      head velocity), values of G were 0.72 +/- 0.07 (counterclockwise) and 0.75 +/-
      0.07 (clockwise) for roll impulses, 0.97 +/- 0.05 (up) and 1.10 +/- 0.09 (down)
      for pitch impulses, and 0.95 +/- 0.06 (right) and 1.01 +/- 0.07 (left) for yaw
      impulses (mean +/- 95% confidence intervals). 4. The eye rotation axis was well
      aligned with head rotation axis during roll, pitch, and yaw impulses: delta
      remained almost constant at approximately 5-10 degrees, so that the spatial
      misalignment angles were < or = 5 degrees. delta was 9.6 +/- 3.1
      (counterclockwise) and 9.0 +/- 2.6 (clockwise) for roll impulses, 5.7 +/- 1.6
      (up) and 6.1 +/- 1.9 (down) for pitch impulses, and 6.2 +/- 2.2 (right) and 7.9
      +/- 1.5 (left) for yaw impulses (mean +/- 95% confidence intervals). 5. VOR gain
      (gamma) is the product of G and cos(delta). Because delta is small in normal
      subjects, gamma is not significantly different from G. At 80 ms after the onset
      of an impulse, gamma was 0.70 +/- 0.08 (counterclockwise) and 0.74 +/- 0.07
      (clockwise) for roll impulses, 0.97 +/- 0.05 (up) and 1.09 +/- 0.09 (down) for
      pitch impulses, and 0.94 +/- 0.06 (right) and 1.00 +/- 0.07 (left) for yaw
      impulses (mean +/- 95% confidence intervals). 6. VOR latencies, estimated with a
      latency shift method, were 10.3 +/- 1.9 (SD) ms for roll impulses, 7.6 +/- 2.8
      (SD) ms for pitch impulses, and 7.5 +/- 2.9 (SD) ms for yaw impulses. 7. We
      conclude that the normal VOR produces eye rotations that are almost perfectly
      compensatory in direction as well as in speed, but only during yaw and pitch
      impulses. During roll impulses, eye rotations are well aligned in direction, but
      are approximately 30% slower in speed.

PMID- 8985897
TI  - Three-dimensional vector analysis of the human vestibuloocular reflex in response
      to high-acceleration head rotations. II. responses in subjects with unilateral
      vestibular loss and selective semicircular canal occlusion.
AB  - 1. We studied the three-dimensional input-output human vestibuloocular reflex
      (VOR) kinematics after selective loss of semicircular canal (SCC) function either
      through total unilateral vestibular deafferentation (uVD) or through single
      posterior SCC occlusion (uPCO), and showed large deficits in magnitude and
      direction in response to high-acceleration head rotations (head "impulses"). 2. A
      head impulse is a passive, unpredictable, high-acceleration (3,000-4,000
      degrees/s2) head rotation through an amplitude of 10-20 degrees in roll, pitch,
      or yaw. The subjects were tested while seated in the upright position and
      focusing on a fixation target. Head and eye rotations were measured with the use
      of dual search coils, and were expressed as rotation vectors. A three-dimensional
      vector analysis was performed on the input-output VOR kinematics after uVD, to
      produce two indexes in the time domain: magnitude and direction. Magnitude is
      expressed as speed gain (G) and direction as misalignment angle (delta). 3. G.
      after uVD, was significantly lower than normal in both directions of head
      rotation during roll, pitch, and yaw impulses, and were much lower during
      ipsilesional than during contralesional roll and yaw impulses. At 80 ms from the
      onset of an impulse (i.e., near peak head velocity), G was 0.23 +/- 0.08 (SE)
      (ipsilesional) and 0.56 +/- 0.08 (contralesional) for roll impulses, 0.61 +/-
      0.09 (up) and 0.72 +/- 0.10 (down) for pitch impulses, and 0.36 +/- 0.06
      (ipsilesional) and 0.76 +/- 0.09 (contralesional) for yaw impulses (mean +/- 95%
      confidence intervals). 4. delta, after uVD, was significantly different from
      normal during ipsilesional roll and yaw impulses and during pitch-up and pitch
      down impulses. delta was normal during contralesional roll and yaw impulses. At
      80 ms from the onset of the impulse, delta was 30.6 +/- 4.5 (ipsilesional) and
      13.4 +/- 5.0 (contralesional) for roll impulses, 23.7 +/- 3.7 (up) and 31.6 +/-
      4.4 (down) for pitch impulses, and 68.7 +/- 13.2 (ipsilesional) and 11.0 +/- 3.3
      (contralesional) for yaw impulses (mean +/- 95% confidence intervals). 5. VOR
      gain (gamma), after uVD, were significantly lower than normal for both directions
      of roll, pitch, and yaw impulses and much lower during ipsilesional than during
      contralesional roll and yaw impulses. At 80 ms from the onset of the head
      impulse, the gamma was 0.22 +/- 0.08 (ipsilesional) and 0.54 +/- 0.09
      (contralesional) for roll impulses, 0.55 +/- 0.09 (up) and 0.61 +/- 0.09 (down)
      for pitch impulses, and 0.14 +/- 0.10 (ipsilesional) and 0.74 +/- 0.06
      (contralesional) for yaw impulses (mean +/- 95% confidence intervals). Because
      gamma is equal to [G*cos (delta)], it is significantly different from its
      corresponding G during ipsilesional roll and yaw, and during all pitch impulses,
      but not during contralesional roll and yaw impulses. 6. After uPCO, pitch
      vertical gamma during pitch-up impulses was reduced to the same extent as after
      uVD; roll-torsional gamma during ipsilesional roll impulses was significantly
      lower than normal but significantly higher than after uVD. At 80 ms from the
      onset of the head impulse, gamma was 0.32 +/- 0.13 (ipsilesional) and 0.55 +/-
      0.16 (contralesional) for roll impulses, 0.51 +/- 0.12 (up) and 0.91 +/- 0.14
      (down) for pitch impulses, and 0.76 +/- 0.06 (ipsilesional) and 0.73 +/- 0.09
      (contralesional) for yaw impulses (mean +/- 95% confidence intervals). 7. The eye
      rotation axis, after uVD, deviates in the yaw plane, away from the normal
      interaural axis, toward the nasooccipital axis, during all pitch impulses. After
      uPCO, the eye rotation axis deviates in same direction as after uVD during pitch
      up impulses, but is well aligned with the head rotation axis during pitch-down
      impulses.

PMID- 8985898
TI  - Tachykinin-mediated modulation of sensory neurons, interneurons, and synaptic
      transmission in the lamprey spinal cord.
AB  - 1. Tachykinin-like immunoreactivity is found in the dorsal roots, dorsal horn,
      and dorsal column of the lamprey. The effect of tachykinins on sensory processing
      was examined by recording intracellularly from primary sensory dorsal cells and
      second-order spinobulbar giant interneurons. Modulation of synaptic transmission
      was examined by making paired recordings from dorsal cells and giant
      interneurons, or by eliciting compound depolarizations in the giant interneurons
      by stimulating the dorsal root or dorsal column. 2. Bath application of
      tachykinins depolarized the dorsal cells. This effect was mimicked by stimulation
      of the dorsal root, suggesting that dorsal root afferents may be a source of
      endogenous tachykinin input to the spinal cord. The depolarization was reduced by
      removal of sodium or calcium from the Ringer, or when potassium conductances were
      blocked, and was not associated with a measurable change in input resistance.
      Dorsal root stimulation also caused a depolarization in the dorsal cells, and
      this effect and that of bath-applied substance P, was blocked by the tachykinin
      antagonist spantide. 3. The tachykinin substance P could reduce inward and
      outward rectification in the dorsal cells, the effect on outward rectification
      only being seen when potassium conductances were blocked by tetraethylammonium
      (TEA). 4. Substance P increased the excitability of the dorsal cells and giant
      interneurons, shown by the increased spiking in response to depolarizing current
      pulses. The increased excitability was blocked by the tachykinin antagonist
      spantide. 5. Substance P modulated the dorsal cell action potential, by
      increasing the spike duration and reducing the amplitude of the
      afterhyperpolarization. The spike amplitude was not consistently affected. 6.
      Stimulation of the dorsal column resulted in either depolarizing or
      hyperpolarizing potentials in the giant interneurons. The amplitude of the
      depolarization was increased by substance P, whereas the amplitude of the
      hyperpolarization was reduced. These effects occurred independently of a
      measurable change in postsynaptic input resistance, suggesting that the
      modulation occurred presynaptically. Paired recordings from dorsal cells and
      giant interneurons failed to reveal an effect of substance P on dorsal cell
      evoked excitatory postsynaptic potentials (EPSPs), suggesting that the
      potentiation of the dorsal column-evoked depolarization was due to an effect on
      other axons in the dorsal column. Dorsal root-evoked potentials could also be
      increased in the presence of substance P, although this effect was less
      consistent than the effect on dorsal column stimulation. 7. These results suggest
      that tachykinins modulate sensory input to the lamprey spinal cord by increasing
      the excitability of primary afferents and second-order giant interneurons, and
      also by modulating synaptic transmission. Tachykinins may result in potentiation
      of local spinal reflexes and also modulation of descending reticulospinal inputs
      to the spinal locomotor network as a result of potentiation of spinobulbar
      inputs.

PMID- 8985900
TI  - Neurons in the ventral intraparietal area of awake macaque monkey closely
      resemble neurons in the dorsal part of the medial superior temporal area in their
      responses to optic flow patterns.
AB  - 1. Neurons in the ventral intraparietal area (VIP) are known to respond to
      translating random dot patterns. Such responses can be explained on the basis of
      the input of the middle temporal area (MT) to this area. Anatomic evidence has
      shown that VIP receives input from the dorsal part of the medial superior
      temporal area (MSTd) also. Neurons in the latter area are though to be involved
      in egomotion because they are sensitive to first-order optic flow components such
      as divergence and rotation. Because of their MT and MSTd input, neurons in VIP
      may be expected to show sensitivity to such first-order optic flow as well. 2.
      The question of whether VIP neurons are selective to translation and/or first
      order optic flow was investigated quantitatively in two awake monkeys by
      recording the responses of 52 visually responsive units and by fitting their
      tuning curves. The responses after presentation of random dot patterns exhibiting
      either expansion, contraction, clockwise rotation, or anticlockwise rotation were
      compared with the responses to translation stimuli tested in eight directions. 3.
      Most VIP neurons showed clear direction-selective responses, particularly to
      expansion but sometimes also to a combination of components (spiral stimuli). 4.
      A typical feature of VIP neurons is that their responses to these optic flow
      components remain when different parts of the receptive field are stimulated
      separately ("scale invariance"). For the most responsive subfield the response
      was on average 93% of the whole field response. For all subfields the mean
      response was on average 64% of the whole field response. 5. To test whether the
      scale invariance arose from convergence of translation-sensitive subfields with
      radial or circular direction preferences ("mosaic hypothesis"), the direction
      selectivity for translating stimuli was tested over these subfields. Basically
      the direction selectivity for translation was unchanged in the various subfields,
      thereby excluding the direction mosaic hypothesis. 6. It is concluded that the
      receptive field characteristics of VIP are very similar to those of MSTd neurons.

PMID- 8985899
TI  - Perceptual and motor processing stages identified in the activity of macaque
      frontal eye field neurons during visual search.
AB  - 1. The latency between the appearance of a popout search display and the eye
      movement to the oddball target of the display varies from trial to trial in both
      humans and monkeys. The source of the delay and variability of reaction time is
      unknown but has been attributed to as yet poorly defined decision processes. 2.
      We recorded neural activity in the frontal eye field (FEF), an area regarded as
      playing a central role in producing purposeful eye movements, of monkeys (Macaca
      mulatta) performing a popout visual search task. Eighty-four neurons with
      visually evoked activity were analyzed. Twelve of these neurons had a phasic
      response associated with the presentation of the visual stimulus. The remaining
      neurons had more tonic responses that persisted through the saccade. Many of the
      neurons with more tonic responses resembled visuomovement cells in that they had
      activity that increased before a saccade into their response field. 3. The visual
      response latencies of FEF neurons were determined with the use of a Poisson spike
      train analysis. The mean visual latency was 67 ms (minimum = 35 ms, maximum = 138
      ms). The visual response latencies to the target presented alone, to the target
      presented with distractors, or to the distractors did not differ significantly.
      4. The initial visual activation of FEF neurons does not discriminate the target
      from the distractors of a popout visual search stimulus array, but the activity
      evolves to a state that discriminates whether the target of the search display is
      within the receptive field. We tested the hypothesis that the source of
      variability of saccade latency is the time taken by neurons involved in saccade
      programming to select the target for the gaze shift. 5. With the use of an
      analysis adapted from signal detection theory, we determined when the activity of
      single FEF neurons can reliably indicate whether the target or distractors are
      present within their response fields. The time of target discrimination
      partitions the reaction time into a perceptual stage in which target
      discrimination takes place, and a motor stage in which saccade programming and
      generation take place. The time of target discrimination occurred most often
      between 120 and 150 ms after stimulus presentation. 6. We analyzed the time
      course of target discrimination in the activity of single cells after separating
      trials into short, medium, and long saccade latency groups. Saccade latency was
      not correlated with the duration of the perceptual stage but was correlated with
      the duration of the motor stage. This result is inconsistent with the hypothesis
      that the time taken for target discrimination, as indexed by FEF neurons,
      accounts for the wide variability in the time of movement initiation. 7. We
      conclude that the variability observed in saccade latencies during a simple
      visual search task is largely due to postperceptual motor processing following
      target discrimination. Signatures of both perceptual and postperceptual
      processing are evident in FEF. Procrastination in the output stage may prevent
      stereotypical behavior that would be maladaptive in a changing environment.

PMID- 8985901
TI  - Repeated tetanic stimulation in piriform cortex in vitro: epileptogenesis and
      pharmacology.
AB  - 1. Focal cortical epilepsy was investigated by applying tetanic stimulation
      repeatedly (100 Hz. 2 s in duration, once every 10 min, 10 episodes) to layer III
      association fibers in rat piriform cortex slices and recording both extracellular
      and intracellular responses from the endopiriform nucleus. To promote
      excitability, piriform slices were incubated in artificial cerebrospinal fluid
      (ACSF) containing 0.9 mM Mg2+ and 5 mM K+, at an initial temperature of 10-12
      degrees C, which was allowed to warm passively to room temperature. 2. Responses
      recorded extracellularly in the endopiriform nucleus consisted of two types: weak
      stimulation evoked an early-occurring, small-amplitude, negatively deflecting
      potential; strong stimulation evoked a more complex response comprising both an
      early potential of maximal amplitude and a later-occurring epileptiform potential
      of greater amplitude and longer duration. Late-occurring epileptiform potentials
      were not observed in slices incubated in ACSF at room temperature. 3. Both the
      early potential and the late-occurring epileptiform responses were abolished by
      the non-N-methyl-D-aspartic acid (non-NMDA) subtype of glutamate receptor
      blocker, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM). Application of
      D(-)-2-amino-5-phosphonopentanoic acid (APV; 50 microM) to block NMDA receptors
      was without effect on the early potential but diminished the late-occurring
      epileptiform potential. The late-occurring potential was unable to follow
      stimulation delivered at a frequency of 1 Hz. These results suggest that the
      early potential was generated monosynaptically and dependent solely on the
      activation of non-NMDA receptors, whereas the late-occurring epileptiform
      potential was polysynaptic in origin and possessed both a CNQX- and an APV
      sensitive component. 4. Responses increased progressively in both amplitude and
      duration after tetanic stimulation. The threshold intensity required to evoke the
      complex dual-component potential was reduced by tetanic stimulation. An increase
      in multiunit spiking activity, indicating an increase in synchronous discharges,
      was also observed. A residual potential could be evoked in the presence of CNQX
      (10 microM) after the tetanic stimulation procedure. 5. Spontaneous discharges
      occurred as early as after the first episode of tetanic stimulation and persisted
      for the duration of the experiment. Spontaneous discharges were abolished by
      either CNQX or by a fourfold increase in extracellular Mg2+ concentration, the
      latter reversibly. APV reduced the frequency of spontaneous discharges by 38.6 +/
      9.3% (mean +/- SE). The conventional anticonvulsant drug 5,5-diphenylhydantoin,
      the benzodiazepine receptor agonist midazolam, and the benzodiazepine receptor
      antagonist flumazenil were without effect on the frequency of spontaneous
      discharges. Evoked responses were also unaffected by either 5,5-diphenylhydantoin
      or midazolam. Slices not exposed to cold ACSF, although demonstrating
      potentiation of evoked responses after tetanization did not produce spontaneous
      epileptiform discharges. 6. Intracellular recordings from endopiriform neurons
      revealed the cellular correlates of the extracellular responses. Weak stimulation
      evoked a small-amplitude depolarizing potential. Increasing the intensity of
      stimulation increased the amplitude of this response and also evoked a second
      depolarizing potential of greater amplitude occurring at variable latencies.
      Maximal stimulation evoked an action potential. After tetanic stimuli, responses
      resembling a paroxysmal depolarizing shift consisting of a depolarizing potential
      with superimposed multiple action potentials were evoked reliably. Passive
      membrane properties after repeated tetanic stimulation were not different when
      compared with control. 7. This novel model of in vitro focal cortical epilepsy
      has many features characteristic of conventional kindling including 1)
      progressive nature; 2) reduced threshold to evoke discharges; and 3) persist

PMID- 8985902
TI  - Independent feedback control of horizontal and vertical amplitude during oblique
      saccades evoked by electrical stimulation of the superior colliculus.
AB  - 1. In early local feedback models for controlling horizontal saccade amplitude, a
      feedback signal of instantaneous eye position is continuously subtracted from a
      reference signal of desired eye position at a comparator. The output of the
      comparator is dynamic motor error, the remaining distance the eyes must rotate to
      reach the saccadic goal. When feedback reduces dynamic motor error to zero, the
      saccade stops on target. Two classes of local feedback model have been proposed
      for controlling oblique saccades (i.e., saccades with both horizontal and
      vertical components). In "independent comparator" models, separate horizontal and
      vertical comparators maintain independent representations of horizontal and
      vertical dynamic motor error. Thus, once an oblique desired displacement signal
      is established, the horizontal and vertical amplitudes of oblique saccades are
      under independent feedback control. In "vectorial comparator" models, output
      cells in the motor map of the superior colliculus act as site-specific vectorial
      comparators. For a given oblique desired displacement, a single comparator
      controls the amplitudes of both components. Because vectorial comparator models
      do not maintain separate representations of horizontal and vertical dynamic motor
      error, they cannot exert independent control over the component amplitudes of
      oblique saccades. 2. We tested differential predictions of these two types of
      models by electrically stimulating sites in the superior colliculus of rhesus
      monkey immediately after either vertical or horizontal visually guided saccades.
      We have shown previously that, despite the fixed site of collicular stimulation,
      the amplitude of the visually guided saccades systematically alters the amplitude
      of the corresponding component (horizontal or vertical) of stimulation-evoked
      saccades. However, in the present study, we examined the effect of the visually
      guided saccades on the amplitude of the orthogonal component of stimulation
      evoked saccades. 3. For a fixed site of collicular stimulation, vectorial
      comparator models predict that the initial visually guided saccade will influence
      both components of the ensuing stimulation-evoked saccade via the single feedback
      comparator. By contrast, independent comparator models permit the independent
      manipulation of the horizontal and vertical amplitudes of these oblique
      stimulation-evoked saccades. 4. In total, we collected data from 15 collicular
      stimulation sites. Immediately after either horizontal or vertical visually
      guided saccades of different amplitudes, we measured the horizontal and vertical
      amplitudes of saccades evoked by stimulation of the intermediate or deep layers
      of the superior colliculus. For each site, the duration, frequency, and current
      of the stimulation train were held constant. 5. Under these conditions,
      stimulation-evoked saccades followed visually guided saccades with short latency
      (18.1 +/- 6.7 ms, mean +/- SD). For every stimulation site tested, although the
      amplitude of the component of stimulation-evoked saccades corresponding to the
      direction of the preceding saccade (horizontal or vertical) varied
      systematically, the amplitude of the orthogonal component was roughly constant.
      6. Thus the horizontal and vertical amplitudes of oblique stimulation-evoked
      saccades can be manipulated independently. Moreover, the peak velocity-amplitude
      relationships, the instantaneous velocity profiles, and the ratio of horizontal
      and vertical velocities and durations were very similar to those of visually
      guided saccades. 7. Independent comparator models can readily account for the
      ability to manipulate the amplitude of one component of oblique saccades without
      affecting the other. However, two-dimensional local feedback models that cannot
      exert independent control over the horizontal and vertical amplitudes of oblique
      saccades should be carefully reevaluated.

PMID- 8985903
TI  - Effects of local oscillator frequency on intersegmental coordination in the
      lamprey locomotor CPG: theory and experiment.
AB  - 1. Experiments have been performed on in vitro preparations of lamprey spinal
      cord bathed in D-glutamate, which induces a pattern of activity recorded from
      ventral roots that is similar to that seen in the intact animal during swimming.
      The frequency of fictive swimming increases with increasing D-glutamate
      concentration, but intersegmental phase lag remains unaffected. 2. The effects on
      intersegmental phase lags of unequal activation of the rostral and caudal halves
      of a preparation were determined. Unequal activation was produced by placing a
      diffusion barrier in the middle of the chamber and perfusing the two halves with
      different concentrations of D-glutamate. 3. Within the rostral compartment, the
      phase lag increased from control when the rostral D-glutamate concentration was
      higher than the caudal concentration, and decreased from control when it was
      lower. By contrast, the phase lags within the caudal compartment did not depend
      on the ratio of D-glutamate concentration between the two compartments. 4. The
      frequency of the ventral root activity during differential activation was not
      significantly different from that of control experiments that had the same
      concentration as in the rostral compartment. 5. The results are discussed within
      the context of the mathematical analysis of chains of coupled oscillators by
      Kopell and Ermentrout and other current theories about the mechanisms of
      intersegmental coordination in the lamprey.

PMID- 8985904
TI  - Control of transmission in muscle group IA afferents during fictive locomotion in
      the cat.
AB  - 1. Primary afferent depolarization (PAD) can be evoked by sensory volleys,
      supraspinal commands, or the activity of spinal locomotor networks (locomotor
      related PAD). In this study we investigated the effect of locomotor-related PAD
      and of sensory-evoked PAD on the monosynaptic transmission between the group IA
      muscle afferents and motoneurons in the lumbosacral spinal cord. 2. Six pairs of
      group IA afferents and motoneurons [4 tibialis anterior (TA), 1 medial
      gastrocnemius (MG), 1 lateral gastrocnemius-soleus (LGS)] were successfully
      recorded intracellularly during spontaneous fictive locomotion in the decerebrate
      cat. The membrane potentials of TA axons and motoneurons were maximally
      depolarized during the flexor phase of the locomotor cycle. In MG and LGS pairs,
      the maximum depolarization in IA axons occurred during the flexor phase and, in
      motoneurons, during the extensor phase. There were no antidromic discharges in
      the recorded axons. The effects of locomotor-related PAD on IA transmission were
      evaluated by comparing the unitary excitatory postsynaptic potentials (EPSPs) in
      the motoneuron evoked by the spontaneous orthodromic firing of the group IA axon
      during the flexor and extensor phases, respectively. In TA pairs, the maximum
      amplitude of unitary EPSPs occurred during the flexor phase when the motoneuron
      and the axon were maximally depolarized. In the MG and LGS pairs, the maximal
      amplitude of unitary EPSPs occurred during the extensor phase when the motoneuron
      was maximally depolarized and when the axon was the least depolarized. Overall,
      the amplitude of unitary EPSPs was clearly modulated during the fictive step
      cycle and always reached a maximum during the depolarized phase of the
      motoneuron, whether the group IA axon was maximally depolarized or not during
      that phase. 3. The effect of sensory-evoked PAD on synaptic transmission was also
      studied in nonlocomoting preparations. One TA pair was successfully recorded and
      PADs were evoked by the stimulation of a peripheral nerve. The amplitude of
      unitary EPSPs in the motoneuron was greatly depressed during the PADs. This
      result is a direct demonstration of the presynaptic inhibition associated with
      the sensory-evoked PAD in the monosynaptic reflex pathway of the cat. 4. We
      conclude from these results that the locomotor-related PAD did not contribute
      significantly to the modulation of transmission in the monosynaptic reflex
      pathway of the cat during fictive locomotion. On the other hand, the results
      confirmed that PAD evoked by sensory input decreases group IA afferent
      transmission efficiently most probably by presynaptic inhibition. The results
      suggest therefore that, during real locomotion, sensory feedback induced by the
      moving limbs or perturbations will evoke an important presynaptic inhibition of
      the release from group IA primary afferent terminals.

PMID- 8985905
TI  - Changes in the responsiveness of parabrachial neurons in the arthritic rat: an
      electrophysiological study.
AB  - 1. Rats rendered polyarthritic by injection of Mycobacterium butyricum into the
      tail were used as a model for the study of "chronic pain". In such rats,
      anesthetized with halothane in a nitrous oxide-oxygen mixture, spontaneous
      activity and responses of parabrachial (PB) neurons to somatic stimulations were
      studied in comparison with those in a control group of healthy animals processed
      under the same experimental conditions. 2. The size of the somatic receptive
      field of PB neurons was similar in both arthritic and control groups. In the
      control group 13%, 55%, and 32% of the receptive fields were small, medium, and
      large, respectively. Similarly, in the arthritic group, 10%, 60%, and 30% of the
      receptive fields were small, medium, and large, respectively. 3. The spontaneous
      activity was significantly (P < 0.001) increased in the arthritic rats (0.1 < 3 <
      16 Hz, n = 31; 10th percentile < median < 90th percentile) in comparison with the
      healthy rats (0.03 < 0.3 < 5 Hz, n = 22). 4. The sensitivity to mechanical
      stimuli was markedly increased in arthritic compared with healthy rats: 1)
      although PB neurons in normal rats never responded to innocuous stimuli, several
      PB neurons in arthritic rats responded to touch and/or joint movement; 2) the
      mean mechanical threshold decreased from 15.8 N/cm2 in normal rats to 5.9 N/cm2
      in arthritic rats; 3) the mean pressure evoking 50% of the maximum response
      decreased from 34 N/cm2 in normal rats to 21 N/cm2 in arthritic rats; and 4) the
      intensity of the maximum response increased from 15.7 Hz in normal rats to 26.3
      Hz in arthritic rats. 5. The mechanical encoding properties were clearly modified
      in arthritic rats compared with healthy rats. In this latter group, the PB
      neurons exhibited a clear capacity to encode mechanical stimuli in the noxious
      range: 1) the stimulus-response curves were always positive and monotonic until
      48 N/cm2; and 2) the slope of the mean curve increased progressively from 2 to 8
      N/cm2 before reaching a roughly linear maximum for a wide range of pressure (8-64
      N/cm2) and plateauing beyond. In the arthritic rat, the PB neurons also encoded
      mechanical stimuli, but clearly from a lower pressure range: the slope of the
      mean curve was maximum and remained steep from the lowest pressure tested (1
      N/cm2) up to 16 N/cm2; afterward the slope decreased progressively from 16 to 64
      N/cm2 before plateauing. 6. The sensitivity to heat stimuli was only weakly
      modified. The thermal threshold was weakly, but significantly, increased from 44
      degrees C in the normal rat to 45.8 degrees C in the arthritic rat. Other
      parameters for thermal modality were not changed, with the mean stimulus-response
      curves being similar in both arthritic and normal groups. 7. In conclusion, these
      experiments demonstrate that the activity of PB neurons is clearly changed in
      arthritic rats. These changes are reminiscent of some behavioral and
      electrophysiological modifications observed during arthritis. Considering the
      current literature, it is hypothesized that the PB relay could be responsible, at
      least in part, for several affective-emotional, behavioral, autonomic, and energy
      metabolism changes observed in arthritic rats.

PMID- 8985906
TI  - Eighth nerve activity regulates intracellular calcium concentration of avian
      cochlear nucleus neurons via a metabotropic glutamate receptor.
AB  - 1. Neurons in the cochlear nucleus, nucleus magnocellularis (NM), of embryonic
      and neonatal chicks are dependent on eighth nerve activity for their maintenance
      and survival. Removing this input results in the death of 20-40% of the NM
      neurons and profound changes in the morphology and metabolism of surviving
      neurons. 2. One of the first changes in NM neurons after an in vivo cochlea
      removal is an increase in intracellular calcium concentration ([Ca2+]i).
      Increased [Ca2+]i has been implicated in a number of neuropathologic conditions.
      3. In this study, we orthodromically and antidromically stimulated NM neurons in
      an in vitro brain stem slice preparation and monitored NM field potentials while
      simultaneously assessing the [Ca2+]i of NM neurons using fura-2. 4. During
      continuous orthodromic stimulation, [Ca2+]i of NM neurons remained constant at 80
      nM. In the absence of stimulation, NM neuron [Ca2+]i increased steadily to 230 nM
      by 90 min. Antidromic and contralateral stimulation produced a [Ca2+]i increase
      in NM neurons that was similar in magnitude but slightly more rapid than that
      observed in the absence of stimulation. 5. Addition of the metabotropic glutamate
      receptor (mGluR) antagonists (R,S)-alpha-methyl-4-carboxyphenylglycine or 2-amino
      3-phosphonopropionic acid to the superfusate during continued orthodromic
      stimulation resulted in a dose-dependent, rapid, and dramatic increase in NM
      neuron [Ca2+]i without affecting the postsynaptic field potentials recorded from
      NM. 6. The ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline
      2,3-dione and 2-amino-5-phosphonovalerate eliminated NM field potentials during
      continued orthodromic stimulation but did not result in an increase in [Ca2+]i.
      7. Continuous superfusion of trans-(+/-)-aminocyclopentane dicarboxylate, but not
      glutamate, prevented the increase in [Ca2+]i in the absence of stimulation. 8.
      These results suggest that NM neurons rely on eighth nerve activity-dependent
      activation of a mGluR to maintain physiological [Ca2+]i. Removal of this mGluR
      activation results in an increase in [Ca2+]i that may contribute to the early
      stages of degeneration and eventual death of these neurons.

PMID- 8985907
TI  - Reduction of rostral dorsal accessory olive responses during reaching.
AB  - 1. Rostral dorsal accessory olive (rDAO) neurons are sensitive to light touch but
      have little or no discharge during active movement. We hypothesize that
      sensitivity of the rDAO is reduced during movement. To test this hypothesis, we
      evaluated sensitivity of rDAO neurons as cats reached out and retrieved a handle.
      On selected trials, mechanical or electrical perturbations to the forelimb were
      presented, and responses of rDAO neurons to the disturbances were recorded. 2.
      All rDAO units were highly sensitive to somatosensory stimuli during periods of
      stance. The cells responded to stimuli such as touch to hairs or light taps to
      the platform on which the cat was standing. 3. Discharges of rDAO neurons showed
      little or no synchronization to any aspect of the reaching task. rDAO neurons
      failed to fire to mechanical perturbations of the food handle during retrieval or
      hold phases of the task, even when their receptive fields included the surface of
      the paw in contact with the handle. 4. Electrical stimulation of the skin
      produced the greatest evoked response at all rDAO recording sites when the cats
      were at stance. Stimulation at any time during the reaching task, including
      periods of holding and licking, produced lower-amplitude evoked responses. The
      reduction in evoked response could be large and was restricted to the limb
      performing the task. 5. The data support the hypothesis that the cutaneous
      sensitivity of the rDAO is reduced during behavior. However, the inhibition does
      not appear to be tailored to specific times during the task or to neurons with
      specific receptive field locations on the actively moving limb. The reduction in
      sensitivity is as likely to be dependent on limb posture as on movement. We
      conclude that the rDAO discharge provides the cerebellum with information about
      vibration or contact during stance; it does not provide reliable information
      about undisturbed or disturbed movement. Climbing fiber input from rDAO might be
      useful in the preparation to make a movement, but it is probably not useful for
      correction of movement errors.

PMID- 8985908
TI  - Low-frequency rhythms in the thalamus of intact-cortex and decorticated cats.
AB  - 1. The patterns and synchronization of low-frequency, sleeplike rhythms (slow,
      spindle and delta oscillations) were compared in the intact-cortex and
      decorticated hemispheres of cats under ketamine-xylazine anesthesia.
      Intracellular recordings were performed in intact and decorticated hemispheres
      from 58 rostrolateral thalamic reticular (RE) neurons and from 164
      thalamocortical (TC) neurons in the ventrolateral (VL) nucleus. In the
      decorticated hemisphere, dual intracellular recordings were performed from five
      RE-VL cell couples and from 12 TC cell couples within the VL nucleus. In
      addition, field potentials were simultaneously recorded from the neocortex
      (electroencephalogram) and ipsilateral thalamus [electrothalamogram (EThG)] of
      the intact (right) hemisphere, while EThG was recorded from the VL nucleus of the
      decorticated (left) hemisphere. 2. The slow oscillation (< 1 Hz) was absent in
      all 72 VL cells and in 23 of 25 RE cells from the decorticated hemisphere, as
      well as in the EThG recorded from the VL nucleus in the decorticated hemisphere,
      whereas it was simultaneously present in the cortex and thalamus of the intact
      hemisphere. The remaining two RE neurons (8%) in the decorticated hemisphere
      oscillated in close time relation with the slow oscillation in the cortex and
      thalamus of the opposite hemisphere; averaged activities showed that the onset of
      depolarization in RE cell followed 12 ms after the sharp depth-negative
      (depolarizing) component in the contralateral cortex. We view this result as the
      electrophysiological correlate of a disynaptic excitatory pathway consisting of
      crossed cortical projections, first relayed in contralateral dorsal thalamic
      nuclei. 3. The patterns of thalamic spindles (7-14 Hz) differed between the two
      hemispheres. Whereas the decorticated hemisphere displayed prolonged, waxing and
      waning spindles, the spindles in the intact-cortex hemisphere were short and
      exclusively waning and followed the depth-negative component of cortical slow
      oscillation. This result indicates that the synchronized corticothalamic drive
      associated with the slow oscillation fully entrains thalamic circuits from the
      onset of spindles, thus preventing further waxing. Similar differences between
      waxing and waning and waning spindles were obtained by stimulating with different
      intensities the thalamus in the decorticated hemisphere. 4. Simultaneous
      intracellular recordings from two VL cells or from RE and VL cells showed nearly
      simultaneous spindle sequences in the decorticated hemisphere. 5. The
      hyperpolarization-activated intrinsic delta oscillation (1-4 Hz) of TC cells was
      asynchronous in the decorticated hemisphere. 6. These results strengthen the idea
      that the slow oscillation is cortical in origin; demonstrate a full, short-range,
      intrathalamic synchrony of spindles in the absence of cortex; and indicate that
      the pattern of spindles, a sleep rhythm that is conventionally regarded as purely
      thalamic, is shaped by the corticothalamic feedback.

PMID- 8985910
TI  - Initiation of saccades during fixation or pursuit: evidence in humans for a
      single mechanism.
AB  - 1. In four human subjects, we measured the latency of saccadic eye movements made
      to a second, eccentric target after an initial, foveated target was extinguished.
      In separate interleaved trails, the targets were either both stationary
      ("fixation") or both moving with the same velocity ("pursuit"). For both fixation
      and pursuit trials, we extinguished the first target at randomized times during
      maintained fixation or pursuit and varied the time interval ("gap duration")
      before the appearance of the second target. 2. During both fixation and pursuit,
      the presence of a 200-ms gap reduced the latencies of saccades, compared with
      those obtained with no gap. For two subjects, we imposed additional, intermediate
      gap durations and found that saccade latencies varied as a function of gap
      duration. Furthermore, the latencies of saccades elicited during pursuit
      displayed the same dependence on gap duration as those elicited during fixation.
      3. Our results demonstrate that the "gap effect" observed for saccades made
      during fixation also occurs for saccades made during pursuit. To the extent that
      the gap effect on saccade latency reflects a mechanism underlying the release of
      fixation, our results suggest that the same mechanism is invoked for saccades
      made during pursuit. From the viewpoint of initiating saccades, the existence of
      separate fixation and pursuit systems may be irrelevant.

PMID- 8985909
TI  - Functional parasagittal compartments in the rat cerebellar cortex: an in vivo
      optical imaging study using neutral red.
AB  - 1. The spatial patterns of activation in the rat cerebellar cortex evoked by
      peripheral stimulation were studied in vivo using optical imaging techniques. 2.
      Crus I and Crus II were stained with the pH sensitive dye, neutral red.
      Electrical stimulation of the vibrissae area of the ipsilateral face evoked
      optical responses consisting of parasagittal bands. The bands were 100-300
      microns in width, elongated in the anterior-posterior direction, commonly
      extended across at least two folia, and varied in number from 1 to 7. 3. The
      optical responses were dependent on activation of postsynaptic elements since
      they were decreased substantially by the non-N-methyl-D-aspartate antagonist, 6
      cyano-7-nitroquinoxaline-2,3-dione. The optical bands were shown to correspond
      anatomically with the parasagittal compartments revealed by immunostaining with
      anti-zebrin II. 4. The present study demonstrates that functional parasagittal
      compartments exist in the rat cerebellar cortex and suggests that zebrin-positive
      Purkinje cell subgroups are anatomically related to this functional organization.

PMID- 8985911
TI  - Generation of high-frequency oscillations in local circuits of rat somatosensory
      cortex cultures.
AB  - 1. Rhythmic cortical activity was investigated with intracellular recordings in
      cortex-striatum-mesencephalon organotypic cultures grown for 42 +/- 3 (SE) days
      in vitro. 2. Electrical stimulation of supragranular layers induced a self
      sustained high-frequency oscillation (HFO) in pyramidal neurons and interneurons.
      3. The HFO started 197 +/- 39 ms after stimulation and had a mean duration of 1.0
      +/- 0.2 s and an initial frequency of 38 +/- 2 Hz. A decrease in frequency at a
      rate of 11.5 +/- 2.7 Hz/s started on average 547 +/- 109 ms after the onset of
      the HFO. 4. During the HFO, local interneurons and pyramidal neurons synchronized
      their activities. The synaptic origin of the HFO was confirmed by its reversal
      potential at -57 +/- 4 mV. 5. These results suggest that a self-maintained HFO
      can be induced in local cortical circuits by excitation of supragranular layers.
      This HFO would facilitate synchronization between distant cortical and thalamic
      regions.

PMID- 8985912
TI  - Enhanced NMDAR-dependent epileptiform activity is controlled by oxidizing agents
      in a chronic model of temporal lobe epilepsy.
AB  - 1. Graded N-methyl-D-aspartate receptor (NMDAR)-dependent epileptiform discharges
      were recorded from ex vivo hippocampal slices obtained from rats injected a week
      earlier with an intracerebroventricular dose of kainic acid. Intracellular
      recordings from pyramidal cells of the CA1 area showed that glutamate NMDAR
      actively participated in synaptic transmission, even at resting membrane
      potential. When NMDAR were pharmacologically isolated, graded burst discharges
      could still be evoked. 2. The oxidizing reagent 5,5'-dithiobis(2-nitrobenzoic
      acid) (DTNB, 200 microM, 15 min) suppressed the late part of the epileptiform
      burst that did not recover after wash but could be reinstated by the reducing
      agent tris (2-carboxyethyl) phosphine (TCEP, 200 microM, 15 min) and again
      abolished with the NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV). 3.
      Pharmacologically isolated NMDAR-mediated responses were decreased by DTNB (56 +/
      10%, mean +/- SD, n = 6), an effect reversed by TCEP. 4. When only the fast
      glutamateric synaptic component was blocked, NMDA-dependent excitatory
      postsynaptic potentials (EPSPs) could be evoked despite the presence of
      underlying fast and slow inhibitory postsynaptic potentials (IPSPs). DTNB
      decreased EPSPs to 48 +/- 12% (n = 5) of control. 5. Since a decrease of the
      NMDAR-mediated response by +/- 50% is sufficient to suppress the late part of the
      burst, we suggest that epileptiform activity can be controlled by manipulation of
      the redox sites of NMDAR. Our observations raise the possibility of developing
      new anticonvulsant drugs that would spare alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid-R (AMPAR)-mediated synaptic responses and decrease NMDAR
      mediated synaptic transmission without blocking it completely.

PMID- 8985913
TI  - Dorsal root reflexes in articular afferents occur bilaterally in a chronic model
      of arthritis in rats.
AB  - 1. Chronic arthritis was produced in rats by the injection of incomplete Freund's
      adjuvant into one knee joint. By 3-5 days later the rats had developed unilateral
      swelling of the injected knee and demonstrated bilateral hyperalgesia to radiant
      heat stimuli applied to the foot. 2. In the same rats anesthetized 3-5 days after
      the injection, dorsal root reflexes could be recorded bilaterally from the
      proximal ends of the cut medial articular nerves (MANs) of the knee joint. 3. The
      dorsal root reflexes consisted of large, medium-sized, and small action
      potentials evoked in response to phasic mechanical stimulation of the lateral
      aspect of the knee. The activity was greater in the MAN ipsilateral to the
      injection than in the contralateral MAN. 4. Local application of capsaicin on the
      side ipsilateral or contralateral to the arthritis dramatically reduced the
      dorsal root reflexes recorded from the contralateral MAN, indicating that these
      dorsal root reflexes depended on activity in fine afferent fibers containing
      capsaicin receptors, presumably C fibers. Local application of capsaicin on
      either side did not significantly change the dorsal root reflexes recorded from
      the ipsilateral MAN. These dorsal root reflexes were presumably conducted in
      afferent fibers that lacked capsaicin receptors, including A beta- and A delta
      fibers.

PMID- 8985914
TI  - Two types of BK channels in immature rat neocortical pyramidal neurons.
AB  - 1. The properties of large conductance Ca(2+)-activated K+ channels (BK channels)
      were investigaed in neocortical infragranular pyramidal neurons by the use of
      inside-out patch recordings. Neurons were acutely isolated from slices of newborn
      to 28-day-old rats (P0-P28) by using minimal protease exposure followed by
      trituration with a vibrating glass probe. Two types of BK channels, slow-gating
      and fast-gating, were observed in immature neurons (P0-P5), whereas only slow
      gating BK were found in more mature neurons. Fast-gating BK channels differed in
      conductance, voltage dependence, and kinetics from the slow-gating ones. 2. The
      properties of fast-gating channels included a conductance of 145 +/- 12.9 (SE)
      pS; frequent openings with short mean open times that were relatively voltage
      independent, mean closed times that showed a voltage-dependent increase, a
      voltage-dependent decrease in open probability (Po). The properties of slow
      gating channels contrasted with those of the fast-gating ones, in that the former
      had a conductance of 181 +/- 3.9 pS, longer mean open times that showed a voltage
      dependent increase, mean closed times that showed a marked voltage-dependent
      decrease, a voltage-dependent increase in Po, and slight inward rectification.
      The significance of these developmental variations in channel properties is
      discussed.

PMID- 8985915
TI  - Brain-derived neurotrophic factor blocks long-term depression in rat visual
      cortex.
AB  - 1. Brain-derived neurotrophic factor (BDNF) has been reported to play a role in
      long-term potentiation (LTP) in hippocampus, but whether it is involved also in
      long-term depression (LTD) is not yet known. In this study, we tested whether
      BDNF and its gene family, nerve growth factor (NGF), have any effect on synaptic
      transmission and LTD in visual cortical slices of young rats. 2. An application
      of BDNF at the concentration of 20 ng/ml did not significantly change layer
      II/III field responses evoked by layer IV stimulation at 0.1 Hz, although at 200
      ng/ml it enhanced responses. BDNF at 20 ng/ml prevented LTD of field responses
      from being induced by low-frequency stimulation (1 Hz for 15 min) of layer IV.
      NGF did not have such effects in the same concentration range as that of BDNF. 3.
      The action of BDNF was antagonized by K252a, an inhibitor of receptor tyrosine
      kinases. When K252a alone was applied to slices, LTD of stronger magnitude than
      in control slices was induced by low-frequency stimulation. 4. These results
      suggest that endogeneous BDNF may prevent synapses from being depressed by low
      frequency inputs in the developing visual cortex.

PMID- 8985916
TI  - Electric field suppression of epileptiform activity in hippocampal slices.
AB  - 1. The effects of relatively small external DC electric fields on synchronous
      activity in CA1 and CA3 from transverse and longitudinal type hippocampal slices
      were studied. 2. To record neuronal activity during significant field changes,
      differential DC amplification was employed with a reference electrode aligned
      along an isopotential with the recording electrode. 3. Suppression of
      epileptiform activity was observed in 31 of 33 slices independent of region
      studied and type of slice but was highly dependent on field orientation with
      respect to the apical dendritic-somatic axis. 4. Modulation of neuronal activity
      in these experiments was readily observed at field strengths < or = 5-10 mV/mm.
      Suppression was seen with the field oriented (positive to negative potential)
      from the soma to the apical dentrites. 5. In vivo application of these results
      may be feasible.

PMID- 8985917
TI  - Spontaneous switching between ortho- and antidromic spiking as the normal mode of
      firing in the cerebral giant neurons of freely behaving Lymnaea stagnalis.
AB  - 1. Action-potential generation at sites remote from the cell body leads to
      antidromic firing and occurs in a wide variety of animals and experimental
      circumstances. Remote sites of spike generation may play a role in the functional
      subdivision of the axonal branches of a neuron and are also thought to play a
      role in synaptic integration. 2. Spontaneous ortho- and antidromic firing was
      investigated by recording the electrical activity of somata and axons of a pair
      of identified giant neurons [cerebral giant cells (CGCs)] in freely behaving
      animals. 3. At the soma of each CGC, the shape of the extracellular action
      potential was not constant but jumped between two well-defined levels. Subsequent
      recordings of synchronous firing in both cell bodies showed that the shape of the
      extracellular action potential depended on the firing sequence of the two CGCs.
      4. Simultaneous recordings of the cell body and the main axon of a single CGC
      showed that spontaneous changes in the direction of spike conduction (orthodromic
      or antidromic) occurred. These changes in the direction of spike conduction
      coincided with the changes in the shapes of the extracellular action potentials
      recorded from the somata. 5. These results show that, under physiological
      conditions, spontaneous switching occurs between ortho- and antidromic spiking in
      the CGCs, and that action-potential generation at sites remote from the cell body
      is a physiologically relevant mechanism.

PMID- 8985919
TI  - [Vascular responsiveness of platelet activating factor--with special reference to
      its action in the presence of platelets].
AB  - There have not been as many studies of vascular responsiveness to the platelet
      activating factor (PAF) as one might expect. The mechanism of PAF's action on
      blood vessel contractility has not yet been elucidated. In this study, using the
      isolated perfused arterial segment of the central artery of a rabbit ear and
      autologous platelets, we examined the effects of PAF on the vasocontractile
      response to noradrenaline (NA-R). We obtained the following results: (1) In the
      absence of platelets, i.e., under the conditions of perfusion with modified
      normal Krebs' solution alone, PAF (0.036 to 33 ng/ml) had no significant
      influence on NA-R and basal perfusion pressure (BPP); (2) during infusion of
      platelet rich plasma (PRP) with PAF, NA-R was significantly more augmented, as
      compared with that during infusion of PRP without PAF; (3) there was no
      significant difference between BPP during infusion of PRP alone and that during
      infusion of PRP with PAF; and (4) during infusion of PRP with PAF, NA-R was
      alleviated by the application of ketanserin, a selective 5-HT2 receptor
      antagonist, while this response was little influenced by indomethacin, a cyclo
      oxygenase inhibitor. On the basis of these results, it is possible to conclude
      that PAF acts on blood vessel contractility through platelets, and that 5-HT may,
      at least in part, participate in augmenting NA-R by PRP with PAF rather than
      prostanoids.

PMID- 8985918
TI  - [Intraocular smooth muscle physiology relating to pathogenesis and therapy of
      glaucoma].

PMID- 8985920
TI  - [Analysis of colonic motility by fast Fourier transform].
AB  - Colonic motility curve was continuously recorded in dog using a strain gauge
      force transducer and the curve was analyzed by fast Fourier transform. (1) The
      basic pattern of the colonic motility curve was a gradually increasing and
      decreasing contractile wave. (2) The frequency components of the basic
      contractile wave showed a trimodal distribution with peaks at around 1, 20 and 80
      mHz. (3) The 1 mHz component showed a sine curve and represented the slow, big
      motion in the basic contractile wave. (4) The 20 mHz component represented the
      relatively rapid, gradually increasing and decreasing, big motion in the basic
      contractile wave. (5) The 80 mHz component represented the rapid, small motion in
      the basic contractile wave. (6) The fundamental frequency components of the
      colonic contractile wave were unchanged before and after defecation. (7) For the
      antiperistaltic wave which disappeared during transmission, the peaks of the
      wavelength components weakened during transmission and the wave progressed to a
      multi-modal curve. Our findings indicate that fast Fourier transform is an
      extremely useful method in elucidating colonic motility.

PMID- 8985921
TI  - [Prostaglandins increase the response of intraocular muscle and outflow facility
      of the eye].
AB  - The function and sites of action of prostaglandins (PGs) vary in different animal
      species and tissues. In this study the effects of PGs (E1, E2, F2 alpha ,D2) on
      intraocular muscles and outflow facility of the eye were investigated, using
      enucleated bovine eyes. None of these PGs exogenously applied influenced the
      neuromuscular transmission. By contrast, after treatment with indomethacin, all
      PGs tested contracted the muscle much more than in the absence of indomethacin,
      and under these conditions the PGs potentiated responses to cholinergic nerve
      stimulation. Whereas PGF2 alpha was less potent in the absence of indomethacin,
      PGF2 alpha had more potent action primarily on nerves and partly on muscles after
      treatment with indomethacin. PGs also increased outflow facility of the eye,
      after the treatment with indomethacin. In order to understand the site and action
      of PGs, pretreatment with indomethacin may be useful in the intraocular muscle
      and outflow facility of the eye.

PMID- 8985922
TI  - [Inhibitory effects of glucose utilization by gymnema acids in the guinea-pig
      ileal longitudinal muscle].
AB  - Two substances identified as ((3 beta, 4 alpha, 16 beta, 21 beta, 22 alpha)-21
      tigloxy-16, 22, 23, 28-tetrahydroxyolean-12-en-3-yl-beta D-glucopyranosiduronic
      acid) (GA1) and ((3 beta, 4 alpha, 16 beta, 21 beta, 22 alpha)-21-(2
      methylbutyroxy)-16, 22, 23, 28-tetrahydroxyolean-12-en-3-yl-beta-D
      glucopyranosiduronic acid) (GA2) identified among the gymnemic acids are
      triterpene glycosides extracted from Gymnema sylvestre leaves. We examined the
      effects of GA1 or GA2 on high K(+)-induced contraction in the guinea-pig
      longitudinal muscle. A sustained muscle contraction induced by hyperosmotically
      added 65.4 mM KCI (H-65K+) was suppressed by GA1 or GA2 (7.7 x 10(-5) M).
      Simultaneous measurements of reduced pyridine nucleotide (PNred) or oxidized
      flavin protein (FPox) by the fluorescence technique and of contractile force
      revealed that GA1 and GA2 reduced the increase of PNred fluorescence and
      contractile force induced by H-65K+, whereas FPox fluorescence induced by it
      further increased. Reduced muscle contraction induced by GA1 or GA2 was restored
      by 5.5 mM pyruvate. Simultaneous measurements of intracellular Ca2+ [Ca2+]1 level
      and contractile force indicated that [Ca2+]1 level, which increased by H-65K+,
      hardly changed with GA1 and GA2. In summary, both GA1 and GA2, which are among
      the gymnemic acids, suppressed high K(+)-induced contraction in the guinea-pig
      ileal longitudinal muscle. The difference between these two gymnemic acids was
      not significant. The inhibitory effect of GA1 and GA2 on smooth muscle were
      assumed to be a result of inhibiting glucose uptake, which is an energy source of
      the muscle, whereas the inhibitory mechanisms were probably not mediated by Ca2+.

PMID- 8985923
TI  - Multi-fractionated stereotactic radiotherapy.
AB  - Precision and accuracy of a patient's treatment are key advantages of single
      fraction stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMS)
      and some small brain metastases. These advantages are equally valuable in
      fractionated treatment of the pituitary, brain metastases and brain boost fields.
      The need to implement the preciseness from stereotactic radiosurgery to
      fractionated treatments was recognized. Using our experience with single-fraction
      stereotactic radiosurgery as a model, we developed a multi-fractionated
      stereotactic radiotherapy technique that allows us to immobilize a patient daily
      and implement important existing devices such as the Brown-Roberts-Wells (BRW)
      angiographic localizer, CT scan localizer, and non-coplanar shaped field
      treatment planning. Development of this technique also allows us to achieve
      reproducible patient positioning based on immobilization techniques using
      polyurethane foam immobilization and heat moldable plastic technology without the
      necessity of the invasive technique of skull fixation. The development,
      implementation and dosimetry of this technique will be discussed in this paper.

PMID- 8985925
TI  - Improved dose distribution in the brain by collimator rotation.
AB  - Because the head slopes both in the sagittal and lateral directions, the brain is
      one of the anatomical areas which could benefit by the use of 3-dimensional
      compensators. The fabrication of 3-dimensional compensators is an expensive and
      complex task, and as such, not widely used. A standard wedge is often employed to
      compensate for skull curvature when treating a partial brain area, with the heel
      of the wedge placed either superior or lateral. This usually results in areas of
      over- and under dosage in the planning target volume. However, by rotating the
      collimator 45 degrees while using a standard wedge, with the heel placed superior
      lateral, the dose distribution can be significantly improved.

PMID- 8985924
TI  - Design and production of wax compensators for electron treatments of the chest
      wall.
AB  - The primary aim of electron treatment planning for the post mastectomy chest wall
      is to encompass the volume between the skin surface and the lung-rib interface
      while limiting dose to the lung. Electron energies for treatment of the chest
      wall are chosen based on the thickness of tissue between these two areas.
      Surgical defects or surface irregularities often result in differing thicknesses
      of tissue across the treatment volume, and patient-specific compensation is
      necessary to achieve the desired dose distribution. This is true whether the
      treatment plan is designed using fixed or rotational electrons to treat the chest
      wall. These clinical requirements are often met using custom shaped wax of
      varying thickness which conforms to the chest surface. This paper will discuss
      the treatment planning process used to design these compensators, creation and
      use of an exact duplicate of the patient's chest wall to aid in the production of
      these compensators, the production process itself, and verification of the
      completed compensator.

PMID- 8985926
TI  - Whole-limb irradiation of the lower calf using a six-field electron technique.
AB  - The present work demonstrates utilization of electron beam irradiation for the
      treatment of Kaposi's sarcoma when the full circumference of the lower calf is
      involved, and when the deep lymphatics are negative for disease. The finite
      penetration of the electron beam spares deep tissue, preventing the edema
      associated with photon total limb irradiation. The number of fields with fall-off
      required to produce a uniform dose to a cylindrical anatomic structure was
      studied by calculating dose distributions resulting from two-, four-, and six
      field techniques for a 5-MeV electron beam and a 9 cm diameter cylinder. The
      dosimetry and set-up for the six-field technique is demonstrated by a case study.
      Results show that a six-field electron technique produced a sufficiently uniform
      dose while remaining relatively easy to set up and use to deliver patient
      treatment. For the patient case study, dose distributions for the six-field
      technique showed that (1) the penetration of the 90% dose decreased from 1.5 cm
      for a single field to approximately 1.0 cm for a 5-MeV beam; (2) the surface dose
      increased from approximately 70% to 100%, (3) the dose around the circumference
      of the leg at the depth of 1 cm or less varied from approximately 90% to 120% of
      the prescribed dose; and (4) the prescribed dose was 2.5 times the maximum
      central-axis dose from a single field. The six-field treatment was relatively
      simple to apply and produced an acceptable dose distribution for treatment of
      Kaposi's sarcoma of the lower calf. This treatment should be applicable to other
      sites such as the thigh and arms and for other cutaneous diseases such as
      melanoma.

PMID- 8985927
TI  - A comparison of high-energy oblique lung irradiation techniques.
AB  - The lung cancer death rate in the U.S. rose 440% between 1957-59 and 1987-89,
      from 5.4 to 29.4 per 100,000. While surgical resection of small, localized
      carcinomas offers the best prognosis, only 15-20% of lung cancers fall into this
      category. The remaining 80-85% of patients are generally candidates for radiation
      therapy. Typically, the tumor volume (plus a 2 cm margin) and the mediastinum
      will be irradiated, using parallel opposed anterior and posterior ports, until
      the spinal cord has reached tolerance at 45 Gy. At this point, an off-cord
      lateral or oblique treatment technique will be used to complete the prescribed
      dose to the tumor. The depth to isocenter for oblique ports may easily be 15 cm.
      With this depth, a high-energy x-ray beam seems to be required; however, the beam
      may pass through a significant portion of lung tissue, reducing the equivalent
      depth. Another factor to consider is the build-up region beyond the lower density
      lung tissue. Two different energy beams, 6 MV and 18 MV, were compared for the
      oblique treatment ports. Plans were run using a thorax CT slice of an
      anthropomorphic phantom for parallel opposed oblique fields at these two
      energies, each with and without CT correction. Further data were collected for
      comparison by thermoluminescent dosimetry measurements. This paper describes the
      process and results obtained.

PMID- 8985928
TI  - Verification of a simple point dose calculation method for a dual energy linear
      accelerator with asymmetric jaws.
AB  - Certain fundamental dosimetrical parameters involving the applications of
      asymmetric jaws were investigated. The nominal accelerating potentials (NAPs)
      were found to decrease from 5.1 to 4.2 and from 18.0 to 13.4 for the 6 and 18 MV
      beams, respectively, as the off-axis distance (OAD) increases from 0.0 to 15.0
      cm. The relative beam intensity increases from 1.00 to 1.07 at OAD of 15.0 cm for
      the 6 MV beam, and to 1.02 at OAD of 7.0 cm for the 18 MV beam. The percentage
      depth doses (PDDs) for half-blocked fields of 4 x 4 cm, 10 x 10 cm and 20 x 20 cm
      were found to deviate from those of corresponding symmetric fields by less than
      2% down to the depth of 35.0 cm. The field size factor (FSF) for the asymmetric
      field from 4 x 4 cm to 20 x 20 cm deviates less than 1.0% from those of the
      corresponding symmetric fields. The equivalent square concept was found to be
      applicable to asymmetric fields within 1% error if the jaw exchange effect is
      taken into consideration. The measured point doses for half-blocked fields of 4 x
      4 cm, 10 x 10 cm and 20 x 20 cm for both 6 and 18 MV were within 3% of the
      calculated dose based on a published dose calculation method which employs
      symmetric field beam parameters, such as field size factor (FSF), percentage
      depth dose (PDD), and off-axis correction factors (OAFs). The efficacy of this
      point dose calculation method is discussed.

PMID- 8985929
TI  - The use of diode dosimetry in quality improvement of patient care in radiation
      therapy.
AB  - The purpose of this work is to improve the quality of patient care in radiation
      therapy by implementing a comprehensive quality assurance (QA) program aiming to
      enhance patient in vivo dosimetry on a routine basis. The characteristics of two
      commercially available semi-conductor diode dosimetry systems were evaluated. The
      diodes were calibrated relative to an ionization chamber-electrometer system with
      calibrations traceable to the National Institute of Standards and Technology
      (NIST). Correction factors of clinical relevance were quantified to convert the
      diode readings into patient dose. The results of dose measurements on 6 patients
      undergoing external beam radiation therapy for carcinoma of the prostate on three
      different therapy units are presented. Field shaping during treatments was
      accomplished either by multileaf collimation or by cerrobend blocking. A
      deviation of less than +/-4% between the measured and prescribed patient doses
      was observed. The results indicate that the diodes exhibit excellent linearity,
      dose reproducibility, minimal anisotropy, and can be used with confidence for
      patient dose verification. Furthermore, diodes render real time verification of
      dose delivered to patients.

PMID- 8985930
TI  - The use of a partial transmission shield to reduce the optic chiasm doses during
      radiation therapy treatment of brain tumors.
AB  - Historically, brain tumors have been treated with lateral opposed beams for 40-45
      Gy followed by more conformal reduced fields. Advances in treatment planning
      computers have led to the implementation of conformal non-axial techniques,
      allowing for escalation of dose. In patients where total doses exceed 50 Gy,
      adjacent critical structures can be protected with a partially shielded
      transmission block over the optic nerves and chiasm. By eliminating the conedown
      portion of the treatment a more cost and time effective treatment is achieved.
      Partially shielded blocks can be designed by using cerrobend or multileaf
      collimation. They can be included in the treatment plan and verified by an
      irregular field calculation and/ or thermoluminescent dosimeters.

PMID- 8985931
TI  - Quality assurance procedure on a Huestis Styro-former--stay on the cutting edge.
AB  - A review of variations in block positions on port film vs. simulator film at The
      Nashua Regional Cancer Center, Nashua, NH, prompted the development of a method
      of measuring the accuracy of hot wire cut molds vs. a "test" film. The procedure
      is done at a minimum of once a year, or when accuracy of the block cuts are
      suspect. This simple test insures a high degree of confidence that the resulting
      cut molds are appropriate for the clinical situation and the need to recut blocks
      as a result of an out-of-tolerance Huestis Styro-former is kept to a minimum.

PMID- 8985932
TI  - Dosimetric protocols in radiotherapy: a computer program.
AB  - A computer program to evaluate the dose to water in a specified point for low,
      medium and high energy photon and electron radiotherapeutic beams using different
      ionization chambers, phantom materials and new dosimetric standard protocols has
      been developed. The absorbed dose to air cavity calibration factors of the
      ionization chambers at the radiation quality, the updated physical quantities and
      dosimetric parameters are part of the data base, which is extendable to
      individual users' needs. Moreover, the management software permits comparison of
      different dosimetric protocols and reduction of errors on the dose delivered to
      patients.

PMID- 8985933
TI  - A simple method for verifying activity of iodine-125 seeds in rigid absorbable
      suture.
AB  - A simple system which facilitates the verification of the calibration of iodine
      125 sources in rigid absorbable suture, on the remote traceability basis, was
      developed. It consists of a plastic jig accommodating a sterile closed-end 16
      gauge plastic catheter. The iodine-125 source in rigid absorbable suture is
      placed into the sterile closed-end 16 gauge plastic catheter. The jig fits in a
      standard dose calibrator. The sterility of the strand is maintained while a
      reasonable number of seeds used for an actual implant can be easily measured.
      This is an improvement over the current recommended practice of assaying just one
      separate seed of the same strength designation. This system brings the
      calibration procedure for the rigid sterile seed strands in line with the AAPM TG
      40 recommendation for the rest of radioactive seed products.

PMID- 8985934
TI  - Utilization of iron sources and its possible roles in the pathogenesis of Vibrio
      parahaemolyticus.
AB  - Vibrio parahaemolyticus is an important enteropathogen in Japan, Taiwan and other
      coastal regions. The influence of the regulation of iron on the pathogenesis of
      this pathogen has not been well characterized. The growth of pathogenic and non
      pathogenic strains of V. parahaemolyticus on iron-limited agar plates was
      stimulated by ferritin, lactoferrin and transferrin at 30 microM, and also by
      hemin, hemoglobin and ferric ammonium citrate at 100 microM. Spontaneous iron
      utilizing mutant strains (mutants) were derived from a clinical strain, ST550.
      Compared with the parent strain, lowered virulence was demonstrated for these
      mutants, as assayed by adult mouse and suckling mouse models. The in vivo growth
      and enterotoxigenicity of these mutants were also lower in the suckling mice.
      Adherence of the mutants to excised mouse intestine was lower as demonstrated by
      scanning electron microscopy. The iron-regulated outer membrane protein profile
      also changed in selected mutants. These results indicate that iron-regulated
      outer membrane proteins and other unknown factors associated with iron
      utilization may have profound influences, besides iron acquisition, on the
      pathogenesis of V. parahaemolyticus.

PMID- 8985935
TI  - Migration of Salmonella typhi through intestinal epithelial monolayers: an in
      vitro study.
AB  - This study characterizes the transmigration of enteroinvasive Salmonella typhi in
      vitro, using a human intestinal epithelial cell line as a model of small
      intestinal epithelium. C2BBe cells, a subclone of CACO-2 with a highly
      differentiated enterocytic phenotype, were grown to maturity on Transwell
      filters. S. typhi Ty2 and the vaccine strain, Ty21a, the S. typhi mutant X7344
      and parent strain SB130, and S. typhimurium 5771 in logarithmic phase were
      introduced to the upper chamber of the filter units. Numbers of bacteria in the
      lower chamber, TER and permeability of the monolayer to mannitol were measured
      over time. Monolayers were examined by light, electron and confocal microscopy to
      determine the pathway of bacterial transmigration, and intracellular bacteria
      were estimated by gentamicin assay. Epithelial cell injury was quantified by
      light microscopy. S. typhi transmigrated earlier and in larger numbers than S.
      typhimurium, inducing marked changes in electrical resistance and permeability.
      Unlike S. typhimurium, S. typhi selected epithelial cells in small number and
      caused their death and extrusion from the monolayers leaving holes through which
      S. typhi transmigrated. Ty2 consistently transmigrated in larger numbers and with
      more injury to monolayers than Ty21a. S. typhi crosses the monolayers of C2BBe
      cells by a paracellular route in contrast to the transcellular pathway described
      for other Salmonellae. This may be related to the unique pathophysiology of S.
      typhi infection and the restricted host specificity of this pathogen. In these
      assays the vaccine strain, Ty21a, is slightly less invasive than its parent,
      though more invasive than S. typhimurium.

PMID- 8985936
TI  - Serological characterization of Trichosporon cutaneum and related species.
AB  - Recent molecular biological, chemical, physiological and morphological studies
      indicate that Tri-chosporon cutaneum and related species should be reclassified.
      In this study, antigenic characteristics of the species were determined. The
      results of adsorption experiments revealed that there were at least three
      serological types: I, II and III. Specific factor sera I, II and III were
      prepared on the basis of adsorption experiments and isolates were serotyped by
      cell slide agglutination (CSA). Since the CSA test was difficult to read in some
      strains, the results of the CSA test were compared with the findings from an
      enzyme-linked immunosorbent assay (ELISA). For the ELISA, crude polysaccharide
      antigens prepared from the culture supernatant were used as the antigen. The
      types determined by ELISA correlated well with those determined by the CSA test.
      These data suggest that T. cutaneum and related species have at least three
      serological types, and that the typing can be done by either CSA or ELISA.

PMID- 8985937
TI  - Cooperative anti-Candida effects of lactoferrin or its peptides in combination
      with azole antifungal agents.
AB  - The effects of lactoferrin (LF), an antimicrobial protein secreted in body
      fluids, and its peptides in combination with azole antifungal agents were
      investigated by the micro-broth-dilution method in a study of Candida albicans.
      In the case of LF, its pepsin hydrolysate (LFhyd) or the LF-derived antimicrobial
      peptide Lactoferricin B (LF-B), the concentrations required to inhibit the growth
      of Candida decreased in the presence of relatively low concentrations of
      clotrimazole (CTZ). The minimum inhibitory concentration (MIC) of all azole
      antifungal agents tested was reduced by 1/4-1/16 in the presence of a sub-MIC
      level of each of these LF-related substances. Polyene and fluoropyrimidine
      antifungal agents did not show such a combined effect with these LF-related
      substances. The anti-Candida activity of LF or LF-B in combination with CTZ was
      shown to be synergistic by checkerboard analysis. These results indicate that LF
      related substances function cooperatively with azole antifungal agents against C.
      albicans.

PMID- 8985938
TI  - Role of cell surface glycosaminoglycans of human T cells in human
      immunodeficiency virus type-1 (HIV-1) infection.
AB  - To investigate the role of cell surface glycosaminoglycans (GAGs), including
      heparan sulfate (HS), on HIV-1 infection in human T cells, HIV-1 binding and
      infection were determined after treatment of T-cell lines and CD4+ T cells from
      normal peripheral blood mononuclear cells (PBMC) with GAG-degrading enzyme or a
      GAG metabolic sulfation inhibitor. Heparitinase I (hep I) and sodium chlorate
      prevented binding of HIV-1/IIIB to MT-4 cells as revealed by indirect
      immunofluorescence procedures, thereby inhibiting infection. Hep I was less
      effective in the binding inhibition of the macrophage-tropic strain HIV-1/SF162
      than that of the T-cell line-tropic strain HIV-1/IIIB. The binding of HIV-1/SF162
      was about 100-fold less dependent on cell surface HS than HIV-1/IIIB. Human HTLV
      I positive T-cell lines expressed more HS than HTLV-I negative T-cell lines or
      normal CD4+ T cells when stained with anti-HS mAbs against either native or
      heparitinase-treated HS. With the exception of endo-beta-galactosidase (endo-beta
      gal), GAG-degrading enzymes, including hep I, chondroitinase ABC (chon ABC),
      chondroitinase AC II (chon AC II) and keratanase, did not prevent the binding of
      HIV-1/IIIB to CD4+ T cells from normal PBMC. These results indicate that the cell
      surface HS of human T cells participates in HIV-1 infection by facilitating HIV
      1/IIIB binding to MT-4 cells. In particular, the sulfation of HS chains is
      critical. Since the expression of cell surface HS varies among T cells, which are
      not consistently sensitive to hep I treatment in HIV-1 binding inhibition, other
      GAG-like molecules may also be involved.

PMID- 8985939
TI  - Coxsackievirus B3-induced chronic myocarditis in mouse: use of whole blood
      culture to study the activation of TNF alpha-producing cells.
AB  - The pathogenesis of CVB3-induced chronic myocarditis remains unknown. Activated
      monocytes and macrophages may maintain ongoing inflammation during a persistent
      CVB3 infection and possibly represent the major mechanism leading to chronic
      myocarditis. We decided to study the activation status of cells by studying TNF
      alpha secretion in vitro using whole blood culture in CVB3-induced murine chronic
      myocarditis. Seven DBA/2 +/+ mice and 18 NMRI nu/nu mice were inoculated
      intraperitoneally with 5x10(5) pfu of CVB3, and mice were mock-infected. Thirty
      one days post-infection, all mice were sacrificed, blood samples were obtained
      from the heart, and the heart was removed. Enteroviral genomic detection by RT
      PCR, virus isolation and histological analysis of heart samples were performed.
      Heparinized whole blood (25 microliters) was cultured for 4 hr and 24 hr in
      sterile 96 well-plate containing 225 microliters RPMI in the presence or the
      absence of activators (LPS + PHA). The TNF alpha levels in the whole blood from
      mock-infected DBA/2 (n = 4) and NMRI nu/nu mice (n = 5) were not different. A
      moderate increase of TNF alpha was observed in three out of five DBA/2 mice with
      negative CVB3 that had no histological abnormalities in myocardium. An increased
      level of TNF alpha was found in the sole DBA/2 mouse with positive CVB3 detection
      and chronic myocarditis. An increased level of TNF alpha was found in one out of
      nine NMRI nu/nu mice with positive CVB3 detection and chronic myocarditis and in
      one out of seven mice with positive CVB3 detection exempt of lesions in
      myocardium. In other infected mice, the level of TNF alpha was normal.
      Enteroviral genome was not detected in the blood from infected mice at 31 days
      post-infection. The increased TNF alpha level in some mice may be designed for a
      beneficial inflammatory and immune response, however, an exaggerated release may
      be associated with an adverse effect. The normal TNF alpha level in whole blood
      cultures from mice with chronic myocarditis does not exclude enhanced cytokine
      production at infected loci such as myocardial tissue. This is the first report
      to use whole blood cultures to study the production of cytokines in virus-induced
      disease in a small animal model.

PMID- 8985940
TI  - Molecular epidemiology of Japanese encephalitis virus in Okinawa.
AB  - In order to elucidate the molecular characteristics of Japanese encephalitis (JE)
      virus in Okinawa, 23 strains of JE virus isolated in a 25-year span were
      sequenced for the 240 nucleotides of the C-preM junction region and 111
      nucleotides of the E gene region and compared with those of reference strains
      isolated in mainland Japan. The results of phylogenic analysis showed that
      although all the Okinawan isolates showed more than 96% homology in the
      nucleotide sequence in each region, they were chronologically divided into two
      groups: the old group (nine strains) and a new group (14 strains). On the other
      hand, in a comparison with reference strains in mainland Japan, the Okinawan
      isolates showed more than 94% nucleotide sequence homology in both regions,
      indicating that the Okinawan strains belong to the same genotype as that of JE
      strains in mainland Japan. The nucleotide homology of the old group was
      relatively higher than that of the new group. Among the 14 strains in the new
      group, 13 strains were isolated from mosquitoes collected from a pig farm from
      1986 through 1992. These strains showed higher nucleotide divergence than the old
      group strains, isolated from mosquitoes and swine sera collected at several
      sites, in both regions. A nucleotide substitution at the position 1920 in the E
      gene was identified in three isolates. This substitution generated an aspargine
      proline-threonine sequence capable of serving as an attachment site of
      carbohydrate.

PMID- 8985941
TI  - Production, binding characteristics and protective immunity of monoclonal
      antibody to pneumococcal type-9V conjugate.
AB  - A monoclonal antibody (MAb) to pneumococcal type-9V polysaccharide (PS) was
      produced using PS conjugated to inactivated pneumolysin as the immunogen. The MAb
      to 9V PS was of the IgG1 subclass. The antigen-antibody reaction increased
      rapidly at low concentrations and reached a plateau at 10 micrograms PS/ml as
      measured by nephelometry of the group 9 PS against 9V MAb binding. In contrast,
      the binding of group 9 PS against rabbit 9V antiserum (AS) increased
      proportionally and continued to increase up to the highest concentration of PS
      tested (20 micrograms PS/ml). The 9V MAb reacted with all group 9 PSs (9A, 9L, 9N
      and 9V) by immunodiffusion. In the homologous 9V Ag-MAb reaction, there were
      marked differences in the inhibition of binding by the cross-reactive 9L PS
      (19.2% inhibition) and the 9N PS (0.2%). In contrast, inhibition of the
      homologous 9V Ag-rabbit AS binding by cross-reactive 9L and 9N PSs ranged from
      57.8 to 62.7%. Removal of the O-acetyl group from 9V PS by alkali hydrolysis
      resulted in decreased binding with rabbit 9V AS. However, the binding reaction
      with 9V MAb was less affected by the loss of O-acetyl content. The 9V MAb was
      both opsonic and passively protected young mice against challenge with type-9V
      pneumococci.

PMID- 8985942
TI  - Rapid identification of mutans streptococcal species.
AB  - Mutans streptococci are considered the predominant pathogens in dental caries.
      Three methods, i.e. dot blot hybridization analysis, PCR analysis and SDS-blue
      dextran-PAGE, were examined for identifying mutans streptococcal species. In dot
      blot hybridization, DNA probe derived from the dextranse gene (dexA) of
      Streptococcus mutans hybridized with different intensities under the condition of
      low stringency against each species of mutans streptococci although the dexA
      probe was specific for S. mutans under the condition of high stringency.
      Oligonucleotide primers for polymerase chain reaction (PCR) were designed on the
      basis of the dexA DNA sequence. The primers amplified species-specific PCR
      products in the reference species (15 strains of 5 species) of mutants
      streptococci. An electrophoretic profile of dextranases from the mutans
      streptococci on SDS-blue dextran-PAGE also showed species-specific behavior.
      These results suggest that the three identification methods examined here are
      useful for distinguishing the species of mutans streptococci and also indicate
      that PCR analysis is suitable for simple, rapid and reliable identification of
      mutans streptococcal species.

PMID- 8985943
TI  - An epidemiological study of Salmonella enteritidis by pulsed-field gel
      electrophoresis (PFGE): several PFGE patterns observed in isolates from a food
      poisoning outbreak.
AB  - An epidemiological analysis of Salmonella enteritidis from a food poisoning was
      done using pulsed-field gel electrophoresis (PFGE) of BlnI- or XbaI-digested
      fragments of chromosomal DNA of isolates. S. enteritidis isolates obtained from
      19 patients had identical PFGE patterns. Therefore, a strain giving the same
      pattern was considered to be the causative agent of this outbreak. In addition,
      four isolates that had different BlnI-digested PFGE patterns were obtained from
      three patients, suggesting that the observed variations in PFGE patterns might
      occur as the result of some point mutations of chromosomal DNA during growth or
      from the existence of several S. enteritidis strains from various sources.
      Subsequent PFGE analysis of continuously subcultured strains supported the former
      possibility. These observations indicate that PFGE analysis on multiple numbers
      of colonies from each patient are necessary for the epidemiologic investigation
      of S. enteritidis.

PMID- 8985944
TI  - Borrelia tanukii sp. nov. and Borrelia turdae sp. nov. found from ixodid ticks in
      Japan: rapid species identification by 16S rRNA gene-targeted PCR analysis.
AB  - Based on the results of RFLP-ribotyping, whole DNA/DNA hybridization and
      phylogenetic analysis of the 16S rRNA gene, we previously defined two genomic
      groups of spirochetes closely related to Borrelia burgdorferi sensu lato: group
      Hk501 for strains isolated from Ixodes tanuki ticks and group Ya501 for strains
      isolated from Ixodes turdus ticks. In this report, we propose that group Hk501
      should be classified as Borrelia tanukii sp. nov. and group Ya501 as Borrelia
      turdae sp. nov. The alignment of previously published Borrelia 16S rRNA gene
      sequences led us to design species-specific PCR primer sets. The primers allowed
      the rapid identification of B. tanukii and B. turdae.

PMID- 8985945
TI  - Differential expression of a Mycobacterium tuberculosis protein recognized by a
      mouse monoclonal antibody.
AB  - Murine monoclonal antibodies were produced against Mycobacterium tuberculosis
      (Mtb) using standard hybridoma procedures. By a whole cell enzyme-linked
      immunosorbent assay (ELISA), one monoclonal antibody (mAb), HB28, demonstrated
      high level specific reactivity to Mtb. Western blot analysis demonstrated
      reactivity to a single 65 kDa Mtb protein in the cell wall extract and culture
      filtrate. HB28 mAb appears to be recognizing a 65 kDa Mtb protein that is over
      expressed by Mtb but not other species under certain culture conditions.
      Differential expression and detection of this protein by HB28 mAb may have
      potential for diagnostic applications.

PMID- 8985946
TI  - Magnetic field gradients in the MRI suite and their effects on aneurysm clips.
AB  - We studied magnetic field intensity in the magnetic resonance imaging suite at
      our hospital and its possible effect on several different types of aneurysm
      clips, including one Heifetz 17-7 PH, six Heifetz Elgiloy, one Mayfield, six
      Perneczky, fifteen Sugita, one Sundt-Kees Variangle, four Variangle-McFadden and
      fifteen Yasargil clips. We carefully observed the clips for any translational or
      rotational movements along the path from the door towards the magnetic resonance
      imaging gantry. The magnetic field strength was 0.04 kiloGauss at the entrance of
      the room, with an acute increase of magnetic strength at 310 cm away from the
      entrance to the room, 90 cm to the entrance of the gantry. The magnetic strength
      continued to increase at a rate of 1.0-1.5 kiloGauss for every 20 cm up to the
      entrance to the gantry. No movement was observed in any of the clips at the
      entrance to the suite except for the Heifetz 17-7 PH clip, which showed small
      movement in the longitudinal plane of the clip. At the entrance to the gantry,
      the Heifetz 17-7 PH, Sundt-Kees Variangle, and Mayfield clips were aligned on the
      walls of the test container perpendicular to the magnetic bore. The, Heifetz
      Elgiloy, Perneczky, Sugita, Variangle-McFadden, and Yasargil clips showed no
      movement throughout the path of the stretcher or near the gantry.

PMID- 8985947
TI  - Analysis of interobserver disagreement in the assessment of subarachnoid blood
      and acute hydrocephalus on CT scans.
AB  - The purpose of this study was to analyse factors for interobserver disagreements
      in two scales used for the assessments of the amount of blood in subarachnoid
      space (Fisher grading) and of acute hydrocephalus on computerized tomographic
      (CT) scans. The assessments made by four neuroradiologists on 59 CT scans
      obtained in the acute stage after subarachnoid hemorrhage were analysed by a
      statistical method by Svensson and Holm. This method permits the separation of
      the inter-observer disagreements in their random and systematic components. The
      overall consistency of the assessments was significant (p < 0.0005) but the
      neuroradiologists disagreed on half of the CT-scans. The kappa values were 0.50
      0.63. The analysis showed that the main reason for disagreements was systematic
      inter-observer differences in their use of the clinically most important parts of
      staging, i.e. subarachnoid clot or intraventricular blood (Fisher grading) and
      too low categories (hydrocephalus). The main conclusion from this study is that
      the proper remedy for Fisher grading and for grading of hydrocephalus is a
      sharpening of the criteria of specific category levels and given this improvement
      both grading systems will show a high level of reliability.

PMID- 8985948
TI  - MR imaging and CT of pituitary abscess: case report and review.
AB  - Pituitary abscess is a rare disorder. However, preoperative diagnosis is
      important to prevent a cranial approach leading to severe meningitis. A case of a
      55 year-old woman with pituitary abcess is reported. The patient was admitted
      with a several-week history of frontal headache and no signs of inflammation.
      Computed tomographic (CT) scan showed a slightly low-density suprasellar
      expanding mass lesion with an enhanced thin wall in the pituitary region.
      Magnetic resonance imaging showed a homogenous high-intensity signal relative to
      brain parenchyma on T1-weighted images with an enhanced thin wall and a
      homogenous low-intensity signal on T2-weighted images. This was histologically
      shown to be a pituitary abscess. Our case and review of the available literature
      suggest that pituitary abscess generally shows a homogenous low-density on CT
      scan and a homogenous low- to iso- and high-intensity signals or homogenous high-
      and low-intensity signals on T1- and T2-weighted images, respectively, with a
      cystic appearance and enhanced smooth wall.

PMID- 8985949
TI  - Cytotoxic effect of Ca++ released from intracellular stores during cerebral
      energy deprivation.
AB  - The increase in cytoplasmatic calcium concentration during cerebral ischemia has
      been proposed as a key event leading to neuronal death. In order to investigate a
      possible role of calcium-release from intracellular stores in ischemic neuronal
      injury, intracellular calcium pools were depleted prior to ischemia by the use of
      thapsigargin. Evoked activity (population spike) in rat hippocampal slices was
      monitored during a 30 min control period, 9 min of energy deprivation and 60 min
      of recovery. The population spike recovered to 27% (17-33) (median and 95%
      confidence interval) following energy deprivation in normal calcium, to 56% (50
      58) in calcium-free incubation fluid and to 83% (75-88) in slices pretreated with
      1 microM thapsigargin. Combining calcium removal and thapsigargin pretreatment
      did not improve recovery further. Both removal of extracellular calcium and
      emptying intracellular calcium stores prior to energy deprivation thus improved
      functional recovery following energy deprivation, however the latter was more
      effective. These results suggest that calcium release from intracellular stores
      may be of major importance in calcium-related neuronal injury during cerebral
      ischemia.

PMID- 8985950
TI  - The time course of glucose metabolism in rat cerebral ischemia with middle
      cerebral artery occlusion-reperfusion model and the effect of MK-801.
AB  - Following cerebral ischemia, the extracellular concentration of excitatory amino
      acids increases, and the excitatory cell death may play an important role
      contributing to ischemic neuronal damage. Although sequential metabolic changes
      in permanent local cerebral ischemia have been reported, the effect of
      reperfusion in local cerebral ischemia on glucose metabolism is less clear. In
      order to investigate the time course change of glucose metabolism in a middle
      cerebral artery occlusion-reperfusion model and the effect of dizocilpin (MK-801)
      on glucose metabolism, the 14C-Deoxyglucose method was used. Hypermetabolism
      occurred at 30 min after the middle cerebral artery (MCA) occlusion, and reached
      a peak at 60 min after ischemia in both ischemic core and penumbra. The shift
      from hyper- to hypometabolism was observed after the ischemia. The reperfusion
      facilitated the decrease of cerebral glucose metabolism in the ischemic region
      following 2 h of MCA occlusion. The pretreatment of MK-801 (0.4 mg kg-1)
      inhibited both increased glucose metabolism during ischemia and decreased glucose
      metabolism during reperfusion. These findings support the hypothesis that
      excitation-induced hyper-metabolism plays a major role in the ischemic insult
      following focal cerebral vascular occlusion.

PMID- 8985951
TI  - Pretreatment with NMDA receptor antagonist MK801 improves neurophysiological
      outcome after an acute spinal cord injury.
AB  - The post-traumatic release of excitatory amino acids (EAA) and their actions on N
      methyl-D-aspartate (NMDA) receptors plays a major role in the spinal cord
      secondary injury process. The neuronal damage caused by the release of EAA may be
      reduced by NMDA-receptor channel blockers. To investigate the involvement of NMDA
      receptors in spinal cord injury (SCI), we pretreated animals with the
      noncompetitive NMDA antagonist MK801 (1.0 mg kg-1) before a compressive acute
      SCI. Pretreated animals with MK801 significantly (p = 0.038) improved the
      recovery of function as measured by evoked potential activities. Morphologically,
      specimens from rats treated with MK801 were characterized by milder and more
      localized hemorrhage in the gray matter. Immunohistochemical staining for glial
      fibrillary acidic protein (GFAP) and neurofilament (NF) histochemistry showed
      leakage of these antigens in traumatized cord while characteristic staining of
      astrocytes and neurons and their processes was observed in morphologically
      preserved tissue. The loss of NF immunoreactivity was reduced by MK801 treatment.

PMID- 8985952
TI  - Normalization of middle latency auditory P1 potential following posterior ansa
      pallidotomy in idiopathic Parkinson's disease.
AB  - The P1 potential (50 msec) of middle latency auditory evoked potential was
      evaluated in seven patients with advanced idiopathic Parkinson's disease before
      and after contemporaneous bilateral posterior ansa-pallidotomy. P1 potential was
      lacking in two patients preoperatively and was prolonged in the remainder of the
      patients when examined in a best medicated 'on' state. All patients showed
      varying degrees of dementia preoperatively on clinical examination. Remarkable
      improvement in their Unified Parkinson's Disease Rating Scale (UPDRS) scores
      during 'on' states from a mean of 45.85 to 14.28 post-operatively was achieved.
      Subsidence of akinetic symptoms, abolishment of dyskinesia, improvement in gait
      freezing, rigidity, and tremors represented main areas of improvement. P1
      latencies and amplitudes reverted back to normal values in six patients including
      the two patients who lacked P1 wave preoperatively. One patient showed mild
      worsening of both Pa and P1 values post-operatively attributed to sleepiness
      during testing, a transient phenomenon commonly encountered following posterior
      ansa-pallidotomy. The post-operative P1 changes were statistically significant
      for both latencies and amplitudes at p = 0.078 and p = 0.073, respectively, for
      all seven patients using one tailed paired t-test. The change in UPDRS post
      operatively best correlated with the post-operative difference in P1;
      specifically, UPDRS subscore II with P1 amplitude (r = -0.068, p = 0.09), and
      UPDRS subscore IV with Pa: P1 ratio (r = +0.77, p = 0.04). Earlier clinical and
      experimental work support the tegmental pedunculopontine nucleus (PPN) as the
      site of origin of P1 wave. In addition, its presence reflects the integrity of
      output cholinergic projection from PPN to both ascending reticular activating
      system ARAS and auditory pathway. We believe this is the first report of
      restoring the integrity of P1 wave following posterior ansa-pallidotomy in
      patients with advanced idiopathic Parkinson's disease. Disinhibition of the PPN
      by posterior ansa-pallidotomy can explain improvements in motor symptoms in view
      of reemergence and normalization of P1 wave form.

PMID- 8985954
TI  - Contralateral evoked brainstem auditory potentials as an indicator of
      intraoperative brainstem manipulation in cerebellopontine angle tumors.
AB  - Brainstem auditory evoked potentials (BAEP) were studied during operations to
      remove acoustic tumors using the retromastoid approach. BAEP were elicited from
      the side contralateral to the tumor, and changes in the latencies of peaks III
      and V of the BAEP were compared with changes in cardiovascular parameters
      throughout the operation. When the changes in the determined cardiovascular
      parameters were related to surgical manipulations, the related changes in the
      latencies of peaks III and V of the BAEP were more consistent than the changes in
      the cardiovascular parameters and they tended to occur earlier than the changes
      noted in the cardiovascular parameters.

PMID- 8985953
TI  - Relationship between the flow pattern and vasomotor reactivity in the ophthalmic
      artery, siphon and vessels within the circle of Willis in the unilateral internal
      carotid artery occlusion.
AB  - The aim was to study a relationship between the flow pattern in the ophthalmic
      artery (OA), the siphon and vessels within the circle of Willis. 27 patients, 22
      males and 5 females, mean age 63 +/- 15 years (SD) with unilateral occlusion of
      the internal carotid artery (ICA) were examined by 3-dimensional Transcranial
      Doppler scanner. Flow signals from the OA, the siphon and intracranial vessels
      were registered before and after i.v. injection of 1 g acetazolamide.
      Pathological flow pattern was found in 18 patients in the OA on the occluded side
      consisting of 12 retrograde and 6 isoelectric flow directions. After
      acetazolamide injection retrograde systolic velocities (SV) increased
      significantly (p < 0.01), but anterograde velocities remained unchanged as did 3
      isoelectric flow patterns, 2 turned to retrograde and one to anterograde flow
      direction. In the siphon lower resting anterograde mean velocities (MV) were
      found on both sides (p < 0.05) compared to normal subjects. Six patients had the
      same retrograde flow as in the OA. After acetazolamide MV in the siphon increased
      (p < 0.01) only on the nonoccluded side. Baseline retrograde ophthalmic SV and MV
      in the siphon correlated (p < 0.01 and p < 0.05 respectively) with MV in the
      middle cerebral artery (MCA) according to linear regression analysis (r = 0.78
      and 0.59 respectively). All patients, having impaired vasomotor reactivity (VMR)
      < or = 11% in the anterior cerebral artery (ACA) on the occluded side, had
      pathological flow pattern in the OA. Patients with greatest difference (delta)
      between MV in the ACA on the nonoccluded and occluded side had a tendency to
      anterograde flow (r = 0.56, p < 0.05). Pulsative index (PI) in the ACA on the
      occluded side was lowest in the category with retrograde flow in the OA (0.67 +/-
      0.14) and differed (p < 0.05) from normals and from the category with isoelectric
      and anterograde flow. Correlation of retrograde flow direction in the OA and
      baseline MV in the MCA and low PI in the ACA on the occluded side indicates a
      supplying ophthalmic collateral to the anterior brain circulation. Impaired VMR
      in the ACA on the occluded side in connection with pathological flow pattern in
      the OA may reflect an exhaustion of the ACA as a supplying vessel.

PMID- 8985955
TI  - Abnormalities of collagen cross-linkage in posterior communicating artery
      aneurysms: a preliminary study.
AB  - The collagen of tissues submitted to mechanical load (i.e. arterial wall) is
      characterised by the presence of intermolecular covalent cross-links
      (hydroxylysyl pyridinoline or pyridinoline: PYD; and lysyl-pyridinoline or
      deoxypyridinoline: DPD) which stabilise the molecular structure. In this
      preliminary study we look for quantitative or qualitative alterations of collagen
      cross-linkage in intracranial aneurysms of posterior communicating artery (PCoA)
      which may be considered a site of elective weakening in the intracranial arterial
      circulation, being one of the most frequent locations of intracranial aneurysms
      and of so called "infundibular widening'. We analysed the collagen cross-linkage
      in 6 autopsy samples of intracranial arterial segments of the Circle of Willis
      which were removed from patients whose cause of death was other than cerebral
      hemorrhage, and in 6 samples of intracranial PCoA aneurysms obtained at surgery.
      The analysis of cross-links showed that there was no significant difference in
      collagen and cross-link content between autopic and aneurysmatic samples except
      for PCoA. In autoptic nonaneurysmatic samples of PCoA a lower content of PYD than
      in internal carotid artery (ICA) and a lower content of DPD than in all other
      arterial segments has been demonstrated; moreover a lower content of cross-links
      (DPD + PYD/ Collagen) was evident in nonaneurysmatic PCoA samples when compared
      to other segments (ICA and Anterior Communicating Artery). On the other hand, the
      mean content of DPD was significantly lower in PCoA aneurysms than in
      nonaneurysmatic samples of the artery and moreover, a significantly low content
      of cross-links (DPD + PYD/Collagen) is overemphasised in PCoA aneurysms,
      suggesting that the peculiar lower content of DPD in PCoA arteries may be
      considered the expression of minor resistance of the arterial wall at this site,
      and may be related to the higher incidence of aneurysms or infundibular widening
      of this arterial segment.

PMID- 8985956
TI  - Effect of hyperglycemia on reperfusion-associated recovery of intracellular pH
      and high energy phosphates after transient cerebral ischemia in gerbils.
AB  - Hyperglycemia increases cerebral damage after transient cerebral ischemia. This
      study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the
      relationship of intracellular tissue acidosis and delayed recovery of brain high
      energy phosphates to increased damage during the reperfusion period. Mongolian
      gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2
      h reperfusion. All gerbils were pretreated intraperitoneally with equivalent
      volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4
      grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla
      Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH,
      inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group,
      intracellular pH decreased with ischemia, but most significantly in hyperglycemic
      animals (6.45 +/- 0.15), in which it had not recovered to preischemic levels by
      the end of the reperfusion period (6.8 +/- 0.1 vs 7.04 +/- 0.1, p < 0.05). High
      energy phosphates phosphocreatine-inorganic phosphate and phosphocreatine
      adenosine triphosphate showed partial recovery in all groups throughout the
      reperfusion period; the recovery was not significantly altered by glucose status.
      Hyperglycemia worsened pH but not the recovery of high-energy phosphates in
      animals reperfused after 20 min of transient cerebral ischemia. This sustained
      acidosis may be a primary event in transient damage in hyperglycemic animals.

PMID- 8985957
TI  - Endothelium-dependent relaxation and vasospasm in the single-hemorrhage canine
      model.
AB  - We have investigated the relationship between angiographic vasospasm and the
      ability of spastic vessels to relax in response to agents which promote release
      of endothelium derived relaxing factor. Vasospasm was induced in dogs by the
      'single hemorrhage' technique. Animals received a single intracisternal injection
      of blood, blood activated with thromboplastin or collagen, or inert material, and
      angiograms were obtained day 0 and day 7. Vasospasm was estimated by measuring
      the ratio of the diameter of the vessel before and after treatment. Rings of
      cerebral artery obtained from these animals were suspended in a standard organ
      bath arrangement, contracted with prostaglandin F2 alpha and then treated with
      increasing doses of adenosine triphosphate or bradykinin, both of which cause
      relaxation by an endothelium-dependent process. The arteries from animals with
      moderate to severe vasospasm showed a response to bradykinin and adenosine
      triphosphate which was reduced, absent or converted to a contraction, when
      compared with normal vessels. Vessels in which vasospasm was mild or absent
      relaxed as expected to these agents. The reduction in vessel diameter showed a
      highly significant correlation with the reduction in relaxation to bradykinin or
      adenosine-triphosphate. These results have demonstrated that impairment of
      endothelium-dependent vasorelaxation correlates with the existence of vasospasm.

PMID- 8985958
TI  - Up-regulation of c-myc gene expression following focal ischemia in the rat brain.
AB  - Changes in gene expression including that of c-fos occur following cerebral
      ischemia. Proto-oncogenes c-myc and s-myc and oncosuppressor gene p53 are known
      to induce apoptosis in some types of cells, whereas proto-oncogene bcl-2 inhibits
      apoptosis. Possible induction of mRNAs for c-myc, N-myc, s-myc, c-fos, p53 and
      bcl-2 was examined following focal ischemia in the rat anterior cortex,
      hippocampus, thalamus and cerebellum by Northern blot analysis. Animals were
      decapitated 1, 2, 6, 12, and 24 hours following the left middle cerebral artery
      (MCA) occlusion. In sham-operated control rats, the mRNAs for c-myc, N-myc, c-fos
      and p53 were present in the anterior cortex, hippocampus, thalamus on both sides,
      and in the cerebellum, whereas those for s-myc and bcl-2 were not. The c-myc gene
      expression was rapidly and markedly induced by the MCA occlusion in the
      ipsilateral anterior cortex, hippocampus and thalamus in a time-dependent manner.
      In these regions, the c-fos gene expression was also induced as early as 1 hour
      after the MCA occlusion. The p-53 mRNA was induced in the ipsilateral hippocampus
      at 24 hours after MCA occlusion. In contrast, mRNAs for N-myc, s-myc and bcl-2
      were not induced following MCA occlusion. These results indicate a possibility
      that high-level expression of the c-myc gene may be involved in the ischemic
      cellular events including apoptosis.

PMID- 8985959
TI  - Hemodynamics in an arterial union--simulation study on therapeutic unilateral
      vertebral artery occlusion.
AB  - Hemodynamic changes following unilateral vertebral artery (VA) occlusion were
      investigated in a rat model. The left carotid artery was resected and anastomosed
      to the right side in an end-to-side fashion to create a half-ring bypass. The
      distal side of the bypass was regarded as a union of VAs. Changes in the
      geometry, histology and hemodynamics in the union were investigated after the
      recipient artery was ligated. Intimal thickening was most prominently observed in
      the recipient arterial segment distal to the ligation site, where the lumen was
      obliterated. However, the portion of the lumen within 2.6 +/- 0.6 (mean +/- s.d.)
      mm, a distance of 2.9 +/- 0.6 times the internal diameter from the union, was not
      obliterated. The angle of the union was positively related to the length of this
      residual lumen. The results of this study explain some of the pathogenesis in
      unsuccessful aneurysmal thrombosis or brain stem infarction after therapeutic
      unilateral VA occlusion.

PMID- 8985960
TI  - Sleep promoting effects of intravenously administered acidic fibroblast growth
      factor.
AB  - The influence of acidic fibroblast growth factor (aFGF) on sleep was studied in
      conscious rabbits. An intravenous (i.v.) bolus injection of aFGF induced a
      significant increase in sleep duration in comparison with animals that received
      vehicle solution. Somnogenic effects were obtained 30 min following i.v. aFGF
      administration and lasted about 75 min. Furthermore, the somnogenic effects of
      aFGF were prevented by pretreatment with the nitric oxide synthase inhibitor L
      NAME. Our findings demonstrate a somnogenic effect of aFGF which requires
      crossing the blood-brain barrier (BBB) and implicate that nitric oxide sleep
      pathway may be involved in this biological effect.

PMID- 8985961
TI  - Citicoline for treatment of experimental focal ischemia: histologic and
      behavioral outcome.
AB  - We evaluated the effect of chronic administration of CDP-choline, an intermediate
      of phospholipid synthesis, on outcome from middle cerebral artery occlusion,
      ranging from 30 to 120 min in duration in spontaneously hypertensive rats. Rats
      were randomly assigned to either CDP-choline 500 mg kg-1 or saline. CDP-choline
      treatment was initiated by intraperitoneal injection 15 min after the onset of
      ischemia and continued once a day for 14 days. Morphologic damage and behavioral
      dysfunction (motor and sensorimotor performance) were evaluated, and the maximal
      morphologic damage (Volmax), maximal behavioral dysfunction (BDmax) as well as
      the duration of ischemia producing half-maximal morphologic damage (T50) or
      behavioral dysfunction (BD50) were calculated using a curve-fitting program
      (ALLFIT). Ischemia in control animals produced a Volmax of 103.3 +/- 13.6 mm3.
      CDP-choline did not affect this value (Volmax of 101.6 +/- 11.4 mm3). However,
      CDP-choline significantly extended the T50 from 38.3 +/- 5.9 to 60.5 +/- 4.3 min
      (p < 0.05). Similar to the morphologic outcome, CDP-choline had no effect on
      BDmax but significantly extended BD50 from 41.9 +/- 4.6 to 72.9 +/- 24.5 min (p <
      0.05). Our results suggest that the effectiveness of CDP-choline is greater in
      animals demonstrating submaximal ischemic injury which in this model is produced
      by 30-75 min of ischemia (effect on T50 and BD50), than in animals suffering
      maximal ischemic injury produced by ischemia longer than 75 min (no effect on
      Volmax and BDmax). These results may reflect a threshold of biological membrane
      damage within which CDP-choline is able to restore phospholipid
      content/arrangement and retain membrane integrity.

PMID- 8985962
TI  - An electrical network model of intracranial arteriovenous malformations: analysis
      of variations in hemodynamic and biophysical parameters.
AB  - The propensity of intracranial arteriovenous malformations (AVMs) to hemorrhage
      is correlated significantly with their hemodynamic features. Biomathematical
      models offer a theoretical approach to analyse complex AVM hemodynamics, which
      otherwise are difficult to quantify, particularly within or in close proximity to
      the nidus. Our purpose was to investigate a newly developed biomathematical AVM
      model based on electrical network analysis in which morphological, biophysical,
      and hemodynamic characteristics of intracranial AVMs were replicated accurately.
      Several factors implemented into the model were altered systematically to study
      the effects of a possible wide range of normal variations in AVM hemodynamic and
      biophysical parameters on the behavior of this model and its fidelity to
      physiological reality. The model represented a complex, noncompartmentalized AVM
      with four arterial feeders, two draining veins, and a nidus consisting of 28
      interconnected plexiform and fistulous components. Various clinically-determined
      experimentally-observed, or hypothetically-assumed values for the nidus vessel
      radii (plexiform: 0.01 cm-0.1 cm; fistulous: 0.1 cm-0.2 cm), mean systemic
      arterial pressure (71 mm Hg-125 mm Hg), mean arterial feeder pressures (21 mm Hg
      80 mm Hg), mean draining vein pressures (5 mm Hg-23 mm Hg), wall thickness of
      nidus vessels (20 microns-70 microns), and elastic modulus of nidus vessels (1 x
      10(4) dyn/cm2 to 1 x 10(5) dyn/cm2) were used as normal or realistic ranges of
      parameters implemented in the model. Using an electrical analogy of Ohm's law,
      flow was determined based on Poiseuille's law given the aforementioned pressures
      and resistance of each nidus vessel. Circuit analysis of the AVM vasculature
      based on the conservation of flow and voltage revealed the flow rate through each
      vessel in the AVM network. An expression for the risk of AVM nidus rupture was
      derived based on the functional distribution of the critical radii of component
      vessels. The two characteristics which were used to judge the fidelity of the
      theoretical performance of the AVM model against the physiological one of human
      AVMs were total volumetric flow through the AVM (< or = 900 ml/min), and its risk
      of rupture (< 100%). Applying these criteria, a series of 216 (out of 260) AVM
      models using different combinations of these hemodynamic and biophysical
      parameters resulted in a physiologically-realistic conduct of the model (yielding
      a total flow through the AVM model varying from 449.9 ml/min to 888.6 ml/min, and
      a maximum risk of rupture varying from 26.4 to 99.9%). The described novel
      biomathematical model characterizes the transnidal and intranidal hemodynamics of
      an intracranial AVM more accurately than previously possible. A wide range of
      hemodynamic and biophysical parameters can be implemented in this AVM model to
      result in simulation of human AVMs with differing characteristics (e.g. low-flow
      and high-flow AVMs). This experimental model should serve as a useful research
      tool for further theoretical investigations of a variety of intracranial AVMs and
      their hemodynamic sequelae.

PMID- 8985963
TI  - One in three newly diagnosed cancer patients now receives radiation therapy.

PMID- 8985964
TI  - NCCN pediatric acute lymphoblastic leukemia practice guidelines. The National
      Comprehensive Cancer Network.

PMID- 8985966
TI  - NCCN pediatric neuroblastoma practice guidelines. The National Comprehensive
      Cancer Network.

PMID- 8985965
TI  - NCCN pediatric osteosarcoma practice guidelines. The National Comprehensive
      Cancer Network.

PMID- 8985967
TI  - Severity of xerostomia reduced when Salagen tablets taken during radiation
      therapy.

PMID- 8985968
TI  - Squamous cell carcinoma of the anal margin.
AB  - Based on our experience and a review of the literature, we conclude that
      superficial, well- to moderately differentiated T1 cancers of the anal margin may
      be successfully treated with radiotherapy alone or local excision. Stage T2
      lesions have a significant risk of inguinal lymph node metastases and should be
      treated with radiotherapy to the primary tumor in conjunction with elective
      inguinal lymph node irradiation. The best treatment for T3 and T4 lesions is
      radiotherapy to the primary lesion and regional nodes (inguinal and pelvic)
      combined with concomitant chemotherapy. Abdominoperineal resection (APR) should
      be reserved for patients who have fecal incontinence at presentation or locally
      recurrent disease after previous radiotherapy.

PMID- 8985969
TI  - Hycamtin achieves promising results in study of patients with leukemia.

PMID- 8985971
TI  - Scientists confirm natural resistance to HIV-1.

PMID- 8985970
TI  - Role of radiation therapy in retroperitoneal sarcomas.
AB  - Historically, patients with retroperitoneal sarcomas have had a poor prognosis.
      Surgical resection continues to be the standard treatment for these tumors.
      However, their anatomic location and large size at presentation often make
      complete surgical resection infeasible. Even with complete gross removal of
      tumor, most patients will experience local failure. Adjuvant radiation therapy
      has been used to improve local control rates. In the postoperative setting,
      radiation doses to the tumor bed are limited by radiation tolerances of
      surrounding normal tissues. Extrapolation of data from soft-tissue sarcomas at
      other sites suggests that delivery of higher radiation doses, in combination with
      surgery, may favorably affect local control. Preoperative radiation therapy, in
      combination with brachytherapy or intraoperative radiation therapy at the time of
      surgical resection, allows for the safe delivery of higher doses of radiation
      than is possible in the postoperative setting. These approaches make it possible
      to maximize the likelihood of local control and cure while minimizing normal
      tissue toxicity.

PMID- 8985972
TI  - Cancer pain remedy wins orphan drug status.

PMID- 8985973
TI  - Chemotherapy plus radiation improves prognosis of nasopharyngeal carcinoma.

PMID- 8985975
TI  - Pyrrolidino enaminones structural related to gyrase inhibitors: synthesis,
      cyclization and pharmacological activity.
AB  - The synthesis and stereochemical characteristics of pyrrolidino enaminones with
      structural analogy to quinolone antibacterial agents are reported. Retro-aldol
      reaction of the esters 7 is observed under all conditions of hydrolysis, the
      enzyme catalyzed reaction also does not yield the corresponding acids. In
      contrast to clinically used quinolones exemplary tests with monocyclic esters of
      type 7 and the tricyclic derivative 10 indicate low or no antibacterial activity.
      Additionally to the lack of the carboxylic acid function the enaminones 7 differ
      from quinolones in stereochemical demands and the electronic situation of the
      phenyl substituents of 10, respectively possibly preventing the formation of a co
      operative tetrametric system between compounds and DNA bases.

PMID- 8985974
TI  - The renin-angiotensin-aldosterone system: focus on its distinct role in arterial
      hypertension and its various inhibitors as a therapeutic strategy to effectively
      lower blood pressure.
AB  - Chronically elevated blood pressure results from pathological alterations in
      control systems. Current approaches to elucidate the underlying etiology strongly
      emphasize the (patho)physiological significance of the Renin-Angiotensin
      Aldosterone System (RAAS) which interestingly interacts with the sympathetic, the
      cholinergic and purinergic systems. While the angiotensin-II-receptor subtype 1
      (AT1), which mediates the blood-pressure-related effects of angiotensin II (All),
      has so far been extensively investigated, the physiological relevance of the
      other angiotensin-II-receptor subtypes-in particular of the AT2-receptor subtype
      is about to be evolved by analysis of the various signal transduction mechanisms
      and by evaluation of transgenic animals, e.g. the knock-out mice, following
      disruption of the single A-II-receptor subtypes. Based on the clinical success of
      ACE inhibitors, the blockade of the Renin-Angiotensin-Aldosterone System in many
      different ways has been recognized as a successful strategy to effectively lower
      blood pressure.

PMID- 8985976
TI  - 3-Methylidene-beta-lactams as potential inhibitors of beta-lactamases. Part 1:
      Synthesis of alpha-substituted derivatives from imines by Reformatzky reaction
      with chlorotrimethylsilane, silylation and Peterson olefination.
AB  - A new variation of the Reformatzy reaction with use of I2/zinc and
      chlorotrimethylsilane in THF and a shortened work-up is described allowing the
      synthesis of a wide variety of substituted beta-lactams 3 in fairly good yield.
      These lactams are silylated according to the Peterson reaction yielding by
      reactions with appropriate carbonyl compounds E/Z-mixturs of the substituted 3
      methylidene beta-lactams 7, 8 and 10. The isomers are separated by CC and
      completely characterized by spectroscopic methods, mainly 1H NMR spectroscopy.
      Condensation of the 3-formyl methylidene derivative 10 with amines or malonate
      yields the conjugated products 11, and from the isopropylidene derivative 6 the
      pyridinium sulfonate 14 is prepared via 12 and 13. All methylidene beta-lactams
      are prepared as model compounds for studying their activity against beta
      lactamases and for elucidating the mechanism of action.

PMID- 8985977
TI  - Synthesis, structural analysis and pharmacological effects of N2-substituted 3,4
      dihydrobenzo[h]quinolin-2-amines.
AB  - The introduction outlines possibilities for the design of potentially
      pharmacologically interesting new modifications of phenylethylamine (1) and
      reviews already known and nearly prepared derivatives of 1 with bridged side
      chains. The N2-substituted 3,4-dihydrobenzo[h]quinolin-2-amines 11a-e represent
      bridged beta-azanaphthylethenamines or naphthyl-formamidines. Their synthesis
      started from 3-chloro-N-(1-naphthyl)propionamide (14) and led via
      dihydrobenzoquinolinone 15, thione 19 and methylthiobenzoquinoline hydroiodide
      20. HI as intermediates first to the hydroiodides of 11a-e. Treatment of 11c, d.
      HI with sodium hydroxide yielded the free amines 11c, d. Structure, tautomerism,
      (Z, E)-isomerism and conformation of the prepared benzoquinolines were studied
      and elucidated by one and two dimensional NMR. A synopsis of the manyfold
      pharmacological effects, which were found in the course of the testing of 11a-e.
      HI, completes the paper.

PMID- 8985978
TI  - Covalent binding of acidic drugs via reactive intermediates: detection of
      benoxaprofen and flunoxaprofen protein adducts in biological material.
AB  - The purpose of the study was the direct detection of intact protein adducts
      resulting from in-vitro incubations of flunoxaprofen- and benoxaprofen
      glucuronides in biological materials or originating from in vivo studies-by
      polyacrylamide gel electrophoresis (SDS-PAGE) followed by blotting and
      fluorescent scan, presumably yielding better specificity for the macromolecular
      binding partner and avoiding alkaline cleavage to release the aglycone.
      Glucuronides were isolated from urine samples or generated by incubation of
      aglycone with cofactors and rat liver microsomes. Following dialysis against BSA
      solution, SDS-PAGE and subsequent electrotransblotting were performed.
      Apparently, albumin represents the major binding protein for the covalent binding
      of these acyl glucuronides in plasma following incubation with blank plasma. In
      microsomal proteins two fluorescent peaks (appr. 39 and 62 KD) were identified
      for flunoxaprofen and benoxaprofen incubations. In vivo covalent binding was
      detected for both flunoxaprofen and benoxaprofen in plasma samples. For the
      racemically administered benoxaprofen a slight preponderance in adduct
      concentrations was found for the S-enantiomer. The pharmacokinetic analysis of in
      vivo data obtained for R/S-benoxaprofen (dose: 600 mg racemate) and S
      flunoxaprofen (dose: 100 mg racemate), both of which have been withdrawn from the
      market, (employing a stereospecific HPLC method when analyzing volunteers' and
      patients' samples collected in the last 14 years, yet not stored longer than 3-4
      years) demonstrated that significant amounts of glucuronides occur for both drugs
      (n = 2 for each compound; average Cmax values of the glucuronides: S
      flunoxaprofen: 395 ng/ml; S-benoxaprofen: 775 ng/ml; R-benoxaprofen: 563 ng/ml).
      Presumably because of stereoinversion in humans, aglycone and glucuronide
      concentrations were higher for S- than for R-benoxaprofen. In vivo
      aglycone/glucuronide ratios were smaller for S- than for R-benoxaprofen, although
      in vitro incubation with human liver microsomes resulted in preferential
      glucuronidation of the R-enantiomer of benoxaprofen. Plasma concentration-time
      curves of the glucuronides paralleled those of the respective aglycones in their
      terminal phase. S-Benoxaprofen adduct concentrations were higher than R
      benoxaprofen adduct concentrations (S: 28 ng/ml; R: 18 ng/ml covalently bound)
      and S-flunoxaprofen adduct concentrations with 29 ng/ml in the same range as S
      beoxaprofen adducts, although for the latter the dose range as well as the
      respective glucuronide concentrations were higher. This indicates a higher
      reactivity of S-flunoxaprofen as opposed to S-benoxaprofen glucuronides.

PMID- 8985979
TI  - Purification of transforming growth factor beta 1 from human platelets.
AB  - Transforming growth factor-beta (TGF beta) is a growth and differentiation factor
      which can be released from many cell types. In previous studies, platelets were
      identified as a rich source of TGF beta. Here we present a rapid and convenient
      method for TGF beta purification from human platelets which includes acid-ethanol
      extraction and gelfiltration, cation exchange and reversed phase chromatography.
      All purification steps are performed under acidic conditions to prevent
      adsorption of TGF beta to the vial walls. In addition, volatile solvents and
      buffers were used which allowed easy removal of solvent and salt by
      lyophilization. Using this method pure TGF beta can be easily obtained in high
      yield (370 micrograms) from 20 units of platelet concentrate.

PMID- 8985980
TI  - Developmentally regulated promoters from Dictyostelium discoideum as molecular
      markers for testing potential teratogens.
AB  - Already very early in the course of the development of new pharmaceutically
      relevant drugs toxicological tests are most important. In addition to acute and
      chronic toxicity the estimation of the teratogenic potential is rather crucial.
      We have recently shown that the eukaryotic microorganism Dictyostellium
      discoideum is a useful organism to test the cytotoxicity of chemical compounds.
      Since D. discoideum is competent of undergoing both vegetative growth and
      development, further investigations were aimed to establish a D. discoideum-based
      test system which could predict possible interference of drugs with developmental
      programs. We developed a method which allows to detect and to quantify effects of
      possible teratogens on D. discoideum development. This method is based on
      different transgenic D. discoideum strains, each carrying a bacterial lacZ gene
      under the control of a distinct developmentally regulated D. discoideum promoter.
      Here we describe the effects of the known teratogenic compound valproic acid
      (VPA) on this system.

PMID- 8985981
TI  - Buspirone analogues as ligands of the 5-HT1A receptor. II: Capacity factors as
      chromatographic parameter of lipophilicity evaluation in a series of 5-HT1A and 5
      HT2A receptor ligands.
AB  - The lipophilicity of a series of buspirone related agents was studied by means of
      reversed-phase HPLC using an octadecylsilane stationary phase a mixture of
      aqueous solution of sodium phosphate and methanol as a mobile phase. Comparison
      of the measured capacity factors with log P values has shown very good
      correlations with regression correlation coefficients in the range of 0.994
      0.996.

PMID- 8985982
TI  - Synthesis of novel thiazolo[4,5-d]pyrimidine derivatives for antimicrobial, anti
      HIV and anticancer investigation.
AB  - Some novel thiazolo[4,5-d]pyrimidines containing 6-arylideneamino (3a-e). 2
      dicyanomethylidene (5a), 2-(cyanoethoxy carbonyl) methylidene (5b) or 2-hydrazono
      (7a, b) moieties were synthesized. The prepared compounds were tested in vitro
      for their antibacterial, antifungal, anti-HIV and anticancer activities. Most of
      them showed promising antifungal activity, but only a few compounds exhibited
      anticancer activity.

PMID- 8985983
TI  - 4-Aryl-1-piperazinylalkyl derivatives of 1,2,3,4-tetrahydro-beta-carboline ring
      system. Synthesis and preliminary in vivo studies.
AB  - Three series of compounds containing a 4-aryl-1-piperazinylalkyl fragment
      attached to a different position of the indole (A) or 1,2,3,4-tetrahydro-beta
      carboline (B, C) have been prepared. The quantitative relationship between the
      structure of some derivatives and their sedative effect was found using the Free
      Wilson approach.

PMID- 8985984
TI  - New international F.I.P. method for the determination of the activity of
      Aspergillus oryzae proteases.
AB  - Proteases of Aspergillus oryzae are used as a drug in the therapy of digestive
      disorders. To standardize these enzyme the Enzyme Commission of the Federation
      Internationale Pharmaceutique (F.I.P.) has tested a new determination method,
      which will be described below. The standard preparation of a mixture of
      Aspergillus oryzae proteases used in this test is characterized.

PMID- 8985985
TI  - Interaction of ibuprofen and indomethacin with caffeine.
AB  - The potentiality of interaction of ibuprofen and indomethacin with caffeine was
      investigated by UV and IR spectrophotometry. Differential UV spectrophotometry
      revealed a decrease in optical intensity of the two drugs in presence of caffeine
      as well as a bathochromic shift in the delta max of ibuprofen. On the other hand,
      IR spectrophotometry confirmed such an interaction as evidenced by a marked
      change in the spectra of the two drugs in presence of caffeine. The stoichiometry
      of interaction of the two drugs with caffeine was determined and found to be 2:1.
      The stability constants of the complexes were determined and the complex of
      ibuprofen was found to be more stable. The complexes were prepared by the
      kneading method and the implication of interaction on certain pharmaceutical
      properties of the two drugs was monitored. These included apparent solubility in
      water, dissolution rate, stability, partitioning properties as well as dermal
      diffusion. The results depicted an increase in the apparent solubility of the two
      drugs in water, enhancement in their dissolution properties, increase in
      stability, decrease in their partition coefficients between phosphate buffer (pH
      = 5.5) and n-octanol as well as decrease in their release rate constants through
      abdominal rat skin. The latter result would point out to the limitation of using
      these complexes in transdermal systems.

PMID- 8985987
TI  - SPE-HPLC determination of trimetoprim in tissue samples.

PMID- 8985986
TI  - Synthesis and 3 alpha-hydroxysteroid dehydrogenase inhibitory activity of some
      N(6)-(pyrazol-5-yl)-pyr-azolo[4,3-d]pyrimidin-7-ones.

PMID- 8985988
TI  - A comparison of the effects of cisplatin and cisplatinum (II)phosphonate complex
      on ADP-induced platelet aggregation in vitro.

PMID- 8985989
TI  - The antioxidant properties of captopril.

PMID- 8985990
TI  - Antimicrobial evaluation and chromatographic analysis of some essential and fixed
      oils.

PMID- 8985991
TI  - Natural polyhydroxylated compounds as inhibitors of xanthine oxidase.

PMID- 8985992
TI  - The antimicrobial activity of Tanacetum parthenium extract.

PMID- 8985993
TI  - Relative mortality in lower limb amputees with diabetes mellitus.
AB  - A nationwide epidemiological study included 3516 primary major lower limb
      amputations in diabetic patients, during the period 1982 to 1992. On this well
      defined diabetic amputee population the relative mortality (Standard Mortality
      Ratio, SMR) has been analysed. The mortality rate was found to be 8 times the
      expected during the first year following amputation. The relative mortality is
      higher for females than males. An inverse relation between age and SMR was found,
      and the SMR was significantly related to the level of amputation. No significant
      difference could be detected when analysing SMR in relation to subdiagnosis
      (NIDDM vs IDDM) or SMR in relation to the period of treatment 1982-87 versus 1988
      92.

PMID- 8985994
TI  - Influence of speed on gait parameters and on symmetry in trans-tibial amputees.
AB  - Normal gait is characterised by a high level of inter-leg symmetry of gait
      parameters. Therefore, efforts in rehabilitation of amputees are directed at the
      construction of a prosthesis which provides normal leg function and allows a more
      symmetrical gait. Analysis of the gait of trans-tibial amputees was performed
      when they were ambulating at their own freely selected speed and at a faster
      speed. The effect of speed on selected gait parameters in each leg was evaluated
      and the influence on symmetry established by comparing the inter-leg changes for
      each of the selected parameters. The faster gait trail affected significantly all
      temporal and distance parameters in both legs but not the level of symmetry
      between legs. At the faster speed, the hip angles at heel-strike and during swing
      and the knee angle during load response, in the normal leg, and the knee angle
      during swing in the amputated leg, all increased significantly. Speed of gait
      significantly affected symmetry between knee angles as reflected by the increased
      differences measured during load response (from 2.62 +/- 5.2 to 7.06 +/- 4.2
      degrees) and during toe-off (from 1.80 +/- 7.4 to 9.50 +/- 9.1 degrees). Timing
      and sequence of selected gait events, as related to stride time, were not
      significantly affected by speed of gait. These results might contribute to a
      better understanding of gait characteristics in trans-tibial amputees and provide
      design guidance for prosthetic components.

PMID- 8985995
TI  - Synthesis of a cycloidal mechanism of the prosthetic ankle.

PMID- 8985996
TI  - The use of Methenamine as an antiperspirant for amputees.
AB  - The socket of a prosthesis is a tightly closed container. Sweating inside the
      socket is annoying and may also irritate the skin over the stump or lead to local
      infection such as folliculitis. The most effective method of preventing sweating
      is by the use of astringent agents. Formaldehyde is a very strong astringent but
      is not pleasant to use and may cause skin irritation and systemic reactions.
      Methenamine, in water or when applied to the skin, decomposes to generate
      formaldehyde in small quantities which do not cause side effects. Methenamine was
      used on the stump of sixteen amputees. The trial was conducted as a double blind
      study using two different solutions market as solution A and as solution B. The
      effectiveness of the solutions as an antiperspirant was evaluated clinically by
      the subjects and the physician. Solution A containing Methenamine, was found
      significantly effective, both by the subjects and physician when compared with
      the solution B the blank one. The use of Methenamine as an antiperspirant is
      recommended in amputation stumps.

PMID- 8985997
TI  - Painful neuromata following upper limb amputation.
AB  - Painful neuromata occurring after upper limb amputation are a significant cause
      of stump pain and limit the success of prosthetic training and use. There is
      little information in the literature regarding incidence, consequences or
      outcomes of painful neuromata subsequent to upper limb amputation. This article
      reports an analysis of thirty-two consecutive upper limb amputees. Of these 25%
      had moderate-to-severe stump pain and clinical signs suggestive of neuromata. All
      patients with neuromata were limited in their ability to use a prosthesis prior
      to surgery and following failure of conservative measures, were referred for
      surgical opinion. Six patients have undergone surgical management. The results of
      surgery, with respect to pain and prosthetic usage, are discussed.

PMID- 8985998
TI  - Objective measurement of use of the reciprocating gait orthosis (RGO) and the
      electrically augmented RGO in adult patients with spinal cord lesions.
AB  - The purpose of the study was to measure objectively the home use of the
      reciprocating gait orthosis (RGO) and the electrically augmented (hybrid) RGO. It
      was hypothesised that RGO use would increase following provision of functional
      electrical stimulation (FES). Five adult subjects participated in the study with
      spinal cord lesions ranging from C2 (incomplete) to T6. Selection criteria
      included active RGO use and suitability for electrical stimulation. Home RGO use
      was measured for up to 18 months by determining the mean number of steps taken
      per week. During this time patients were supplied with the hybrid system. Three
      alternatives for the measurement of steps taken were investigated: a commercial
      digital pedometer, a magnetically actuated counter and a heel contact switch
      linked to an electronic counter. The latter was found to be the most reliable
      system and was used for all measurements. Additional information on RGO use was
      acquired using three patient diaries administered throughout the study and before
      and after the provision of the hybrid system. Testing of the original hypothesis
      was complicated by problems in finding a reliable measurement tool and
      difficulties with data collection. However, the results showed that overall use
      of the RGO, whether with or without stimulation, is low. Statistical analysis of
      the step counter results was not realistic. No statistically significant change
      in RGO use was found between the patient diaries. The study suggests that the
      addition of electrical stimulation does not increase RGO use. The study
      highlights the problem of objectively measuring orthotic use in the home.

PMID- 8985999
TI  - Clinical experiences with a convertible thermoplastic knee-ankle-foot orthosis
      for post-stroke hemiplegic patients.
AB  - As rehabilitation for post-stroke hemiplegic patients has become widely accepted
      practice, there has been an increase in patients who are more difficult to treat.
      In the prescription rationale of orthoses for hemiplegics, the knee-ankle-foot
      orthosis (KAFO) for the lower limb has generally been underestimated because of
      its inhibitory effect on the normal walking pattern and also its interference
      with gait training. The authors had an experience of 28 hemiplegics with severe
      physical impairments who were fitted with a convertible plastic KAFO. Among these
      patients, there were 11 cases in which the KAFO was replaced by an ankle-foot
      orthosis (AFO) within 1.5 to 8 months (average 4 months) following initial
      prescription when they were able to control their knee actively. Ambulatory
      capability in these patients was superior to that of the remaining KAFO group.
      The Barthel index of the AFO group patients was higher than the KAFO group (p <
      0.01). However neither age, sex, severity of hemiplegia, starting time of
      rehabilitation following onset of stroke, time of fitting with the orthosis, nor
      the functional recovery stage were critical factors between the two groups, only
      the incidence of major complications affected ambulatory capability.

PMID- 8986000
TI  - Lower limb prosthetic weight limitation.

PMID- 8986001
TI  - Neurapraxia of the common peroneal nerve- a rare complication resulting from
      wearing a KBM prosthesis: a case report.
AB  - This clinical note describes a 47-year-old man who had a traumatic amputation of
      the left lower leg. Two months after wearing a Kondylen Bettung Munster (KMB)
      prosthesis, he developed a compression neuropathy of the common peroneal nerve of
      this right leg after sitting cross-legged. This troublesome complication can be
      avoided by giving accurate information to the patient.

PMID- 8986002
TI  - Multidisciplinary conservative management in classical Volkmann's contracture: a
      case report.
AB  - This clinical note describes the case of a nine-year-old girl with classical
      Volkmann's contracture of the left forearm. The report demonstrates the results
      and follow-up of conservative orthotic management used as a mode of treatment by
      a multidisciplinary team. When using an orthosis it is essential to check
      regularly to attain the desired result.

PMID- 8986003
TI  - Stress, depression and the mesolimbic dopamine system.
AB  - The present review was aimed at re-evaluating results obtained from animal models
      of depression based on experimental stressors in the light of the most recent
      data on the effects of stress on mesolimbic dopamine (DA) functioning. The data
      reviewed reveal that the effects of stressful experiences on behaviour and on
      mesoaccumbens DA functioning can be very different or even opposite depending on
      the behavioural controllability of the situation, the genetic background of the
      organism and its life history. Exposure to a single unavoidable/uncontrollable
      aversive experience leads to inhibition of DA release in the accumbens as well as
      to impaired responding to rewarding and aversive stimuli. Moreover, the data
      reviewed indicate a strong relationship between these neurochemical and
      behavioural effects and suggest that they could model stress-induced expression
      and exacerbation of some depressive symptoms such as anhedonia and feeling of
      helplessness caused by life events as well as syndromal depression provoked by
      traumatic experiences in humans. Repeated and chronic stressful experiences can
      reduce the ability of stressors to disrupt behaviour, induce behavioural
      sensitisation to psychostimulants and promote adaptive changes of mesolimbic DA
      functioning. Opposite neural and behavioural changes, however, can be promoted in
      specific environmental conditions (repeated variable stressful experiences) or in
      genetically predisposed individuals. Thus, depressive symptoms may not represent
      the necessary outcome of stress experiences but be promoted by specific
      environmental conditions and by a genetically determined susceptibility.

PMID- 8986004
TI  - Adrenalectomy attenuates nicotine-induced dopamine release and locomotor activity
      in rats.
AB  - Adrenalectomy (ADX) in mice can potentiate several physiological and behavioural
      responses to nicotine. The present experiments sought to examine this issue in
      this rat by characterising the influence of ADX upon the locomotor depressant,
      activating and dopamine-releasing properties of nicotine. Nicotine (0.8-1.2 mg/kg
      s.c.) dose-dependently depressed locomotor activity, an effect that was
      potentiated by ADX, while the locomotor activating effects of a smaller dose (0.4
      mg/kg) were attenuated by ADX. In both SHAM and ADX rats chronically treated with
      nicotine for 5 days (daily injections of 0.4 mg/kg s.c.), the locomotor
      depressant effects of nicotine did not differ from saline-treated controls.
      Nicotine (0.4 mg/kg s.c.) increased extracellular levels of dopamine in the
      nucleus accumbens. This response was unaffected in rats pretreated with nicotine
      for 5 days (daily injections of 0.4 mg/kg s.c.). However, both ADX groups of rats
      showed smaller increases in dopamine following administration of nicotine. The
      results suggest that depletion of circulating corticosteroids can modulate
      sensitivity to nicotine in rats. The suppressant effects of ADX on nicotine
      induced locomotor activity may be due to its effects on dopamine release in the
      nucleus accumbens.

PMID- 8986005
TI  - Effects of drugs on food- and cocaine-maintained responding, III: Dopaminergic
      antagonists.
AB  - The effects of three dopamine (DA) antagonists (SCH23390, pimozide, and
      chlorpromazine), with various degrees of selectivity for D1 and D2 receptors, and
      an agonist (the cocaine analog, CFT) were studied on responding maintained under
      a multiple fixed-ratio (FR) 30 food, FR30 cocaine (1-100 micrograms/kg per
      injection) delivery, with an interposed 10-min time-out (TO), schedule in rhesus
      monkeys. The effects of each drug depended upon the unit dose of cocaine. With an
      intermediate (10 micrograms/kg per injection) unit dose of cocaine, each
      antagonist decreased rates of responding maintained by either event in a dose
      related manner. At higher (56-100 micrograms/kg per injection) unit doses of
      cocaine, antagonists generally increased and then decreased both food- and
      cocaine-maintained responding in a dose-related manner. These increases appeared
      to result from the blockade of non-specific rate-decreasing effects of self
      administered cocaine, questioning their relevance to the reinforcing effects of
      cocaine. The results failed to support a role for pharmacological selectivity in
      this rate-decreasing effect of cocaine, as both D1 and D2 antagonists were able
      to reverse the effect. In contrast, CFT decreased cocaine-maintained responding
      at doses less than those that decreased food-maintained responding, and failed to
      shift the cocaine dose-effect function to the left. These results, together with
      previous work, suggest that agonists can selectively decrease drug-seeking
      behavior.

PMID- 8986006
TI  - Effects of the calcium channel blocker nimodipine on nicotine-induced locomotion
      in rats.
AB  - The effects of nimodipine, an L-type calcium channel antagonist, on nicotine
      induced locomotor activity were investigated in drug-naive rats. Nicotine (0.4
      mg/kg i.p.) produced significant increases in locomotion following acute
      administration. However, when rats were given injections of nimodipine (5, 10, or
      20 mg/kg i.p.) 1 h prior to the test drug, nicotine-induced locomotor activity
      was altered. Nimodipine 5 mg did not significantly block locomotor activity
      produced by nicotine. In contrast, pretreatment with 10 and 20 mg nimodipine
      significantly blocked nicotine-induced locomotor activity. These findings clearly
      indicate that nicotine-induced locomotion is altered by nimodipine in a dose
      dependent fashion. Results further suggest that the effect of nicotine on
      locomotion is calcium-dependent.

PMID- 8986007
TI  - Effect of chronic treatment with typical and atypical neuroleptics on the
      expression of dopamine D2 and D3 receptors in rat brain.
AB  - The effect of chronic treatment (21 days) with typical and atypical neuroleptics
      on the expression of striatal and limbic D2 and D3 dopamine receptors was
      investigated in rat brain by in situ hybridization and receptor autoradiography.
      Haloperidol and sulpiride increased D2 receptor expression in striatal and limbic
      areas. In contrast, clozapine had no effect on D2 receptor expression.
      Haloperidol decreased D3 receptor expression in limbic areas, with the exception
      of the islands of Calleja where an increase occurred. Sulpiride and clozapine
      increased D3 receptor expression in limbic and striatal regions but decreased D3
      receptor expression in the islands of Calleja. This study demonstrates that
      chronic treatment with typical and atypical neuroleptics produces different
      regionally specific changes in limbic and striatal D2 and D3 receptor expression.
      The alterations in dopamine receptor expression were different for each drug, but
      a distinction between the effects of atypical and typical neuroleptics could be
      made. Comparison of mRNA levels in animals which were not withdrawn from drug
      treatment with those that were withdrawn, demonstrated that some changes in
      receptor expression occurred during drug treatment, whilst others only manifested
      when drug treatment had ceased. The different regulation of dopamine D2 and D3
      receptor expression by typical and atypical neuroleptics may have relevance to
      the ability of these drugs to cause extrapyramidal side-effects.

PMID- 8986008
TI  - Regulation of ionotropic glutamate receptors following subchronic and chronic
      treatment with typical and atypical antipsychotics.
AB  - Quantitative in vitro receptor autoradiography was used to examine changes in
      three ionotropic glutamate receptor subtypes using 3H-MK801 (NMDA-R antagonist),
      3H-CNQX (AMPA-R antagonist) and 3H-kainic acid (kainate-R agonist) following
      subchronic (28 days) and chronic (8 months) treatment of rats with a typical
      antipsychotic, haloperidol (1.5 mg/kg per day), atypical antipsychotic, clozapine
      (25 mg/kg per day), the dopamine D2/D3 receptor antagonist, raclopride (10 mg/kg
      per day), and the dopamine D1 (D1/D5) receptor antagonist SCH23390 (0.5 mg/kg per
      day). Subchronic and chronic drug treatments did not significantly alter 3H-CNQX
      or 3H-kainate binding in any of brain regions examined. Subchronic SCH23390
      treatment elevated 3H-MK801 binding in the hippocampal formation with significant
      increases in the CA1 and dentate gyrus, suggesting a specific role for dopamine
      D1 receptors in the regulation of hippocampal NMDA receptor function. Subchronic,
      but not chronic, haloperidol and clozapine treatment significantly reduced 3H
      MK801 binding in the medial prefrontal cortex. This suggests that typical and
      atypical antipsychotics may exert some of their clinical effects by affecting
      NMDA receptors in the medial prefrontal cortex. Both subchronic and chronic
      clozapine treatment decreased 3H-MK801 binding in the caudate putamen. The
      minimal extrapyramidal side effects produced by clozapine may result, in part,
      from the reduction in NMDA receptor binding in the caudate putamen.

PMID- 8986009
TI  - GABAergic influences on plus-maze behaviour in mice.
AB  - Manipulations of GABA function have been found to produce highly variable effects
      in animal models of anxiety. In the present series, an ethological version of the
      murine elevated plus-maze was used to examine in detail the behavioural profiles
      of diazepam (1.5 mg/kg; positive control) and a range of GABA-related compounds:
      valproic acid (100-400 mg/kg), No-711 (1.25-10.0 mg/kg), muscimol (0.5-3.0
      mg/kg), (+)bicuculline (4.0-8.0 mg/kg), picrotoxin (0.25-2.0 mg/kg), R(+)baclofen
      (0.375-3.0 mg/kg) and CGP 35348 (25-200 mg/kg). On both conventional and
      ethological indices, results confirmed the anxiolytic profile of diazepam under
      present test conditions, and revealed substantially similar effects for the GABA
      T inhibitor, valproic acid (100-400 mg/kg), and the GABAA receptor agonist,
      muscimol (2 mg/kg). The GABA reuptake inhibitor, No-711, produced weak anxiolytic
      like effects at low doses (1.25-2.5 mg/kg) but disrupted behaviour at the highest
      dose tested (10 mg/ kg). Although the GABAA receptor antagonists, (+)bicuculline
      and picrotoxin, produced changes indicative of anxiety enhancement, concomitant
      behavioural suppression was evident at high doses (8 mg/kg and 1-2 mg/kg,
      respectively). Further studies suggested that the effects observed with
      bicuculline may be mediated by an active metabolite, such as bicucine. In
      contrast to the effects of valproic acid and direct GABAA receptor manipulations,
      the GABAB receptor agonist, R(+) baclofen, non-specifically disrupted behaviour
      at the highest dose tested (3 mg/kg) while the GABAB receptor antagonist, CGP
      35348, was inactive over the dose range studied. Although present data confirm
      the sensitivity of the plus-maze to agents which modify GABAA receptor function,
      further studies will be required in order more fully to characterize this
      relationship.

PMID- 8986010
TI  - Phenacetin O-deethylation by human liver microsomes in vitro: inhibition by
      chemical probes, SSRI antidepressants, nefazodone and venlafaxine.
AB  - Biotransformation of phenacetin via O-deethylation to acetaminophen, an index
      reaction reflecting activity of Cytochrome P450-1A2, was studied in microsomal
      preparations from a series of human livers. Acetaminophen formation was
      consistent with a double Michaelis-Menten system, with low-Km (mean Km1 = 68
      microM) and high-Km (mean Km2 = 7691 microM) components. The low-K(m) enzyme
      accounted for an average of 96% of estimated intrinsic clearance, and was
      predicted to contribute more than 50% of net reaction velocity at phenacetin
      concentrations less than 2000 microM. Among index inhibitor probes, alpha
      naphthoflavone was a highly potent inhibitor of the low-Km enzyme (Ki1 = 0.013
      microM); furafylline also was a moderately active inhibitor (Ki1 = 4.4 microM),
      but its inhibiting potency was increased by preincubation with microsomes.
      Ketoconazole was a relatively weak inhibitor (Ki1 = 32 microM); quinidine and
      cimetidine showed minimal inhibiting activity. Among six selective serotonin
      reuptake inhibitor (SSRI) antidepressants, fluvoxamine was a potent inhibitor of
      1A2 (mean Ki1 = 0.24 microM). The other SSRIs were more than tenfold less potent.
      Mean Ki1 values were: fluoxetine, 4.4 microM; norfluoxetine, 15.9 microM;
      sertraline, 8.8 microM; desmethylsertraline, 9.5 microM; paroxetine, 5.5 microM.
      The antidepressant nefazodone and four of its metabolites (meta-chloro
      phenylpiperazine, two hydroxylated derivatives, and a triazoledione) were very
      weak inhibitors of P450-1A2. Venlafaxine and its O- and N-desmethyl metabolites
      showed minimal inhibitory activity.

PMID- 8986011
TI  - Stress reinstates cocaine-seeking behavior after prolonged extinction and a drug
      free period.
AB  - We have shown previously, using an animal model of relapse, that acute exposure
      to intermittent footshock stress induces reinstatement of heroin-taking behavior
      in rats. Here we report that in rats trained to self-administer cocaine, exposure
      to acute intermittent footshock stress induces reinstatement of cocaine-taking
      behavior after prolonged extinction sessions and after a 4- to 6-week drug-free
      period; an effect comparable to that induced by a priming injection of cocaine.
      Animals were initially allowed to self-administer cocaine HCl (1.0 mg/kg per
      infusion, i.v.) during one 3-h session/day for 12 days. Subsequently, extinction
      conditions were introduced by substituting saline for cocaine so that lever
      pressing resulted in i.v. infusions of saline rather than of drug. Extinction
      conditions were maintained until animals made 15 responses or less in the 3 h,
      after which animals were given saline infusions at the start of each daily
      session to establish baseline responding of ten responses or less. Subsequently,
      animals were tested for reinstatement of responding for saline infusions
      following a non-contingent injection of cocaine (2.0 mg/kg, i.v.) and exposure to
      intermittent footshock (10 min, 0.5 mA, 0.5 s on, mean off period of 40 sec).
      After an additional 4- to 6-week drug-free period, tests for reinstatement were
      repeated. Reinstatement of cocaine-taking behavior was observed in both sets of
      tests in response to footshock and cocaine. These results extend previous reports
      from this laboratory that footshock stress is an effective stimulus for
      reinstatement of drug-taking behavior in the rat.

PMID- 8986012
TI  - Microinjections of phencyclidine (PCP) and related drugs into nucleus accumbens
      shell potentiate medial forebrain bundle brain stimulation reward.
AB  - Microinjections of phencyclidine (PCP) into the ventro-medial portion of nucleus
      accumbens in rats potentiated the rewarding impact of lateral hypothalamic brain
      stimulation. Similar effects were found with nomifensine, which shares with PCP
      the ability to block dopamine uptake and thus elevate synaptic dopamine levels
      but does not share with PCP the ability to block NMDA receptors. Similar effects
      were also seen with dizocilpine (MK-801) and [3-((+/-)2-carboxypiperazin-4
      yl)propyl-1-phosphonate] (CPP), which share with PCP the ability to block NMDA
      receptors but not to block dopamine uptake. Thus PCP's properties as a dopamine
      uptake inhibitor and as an NMDA receptor antagonist each appear capable of
      producing reward-related actions in this brain region. The common denominator of
      these two PCP actions is decreased output of medium spiny neurons; these neurons
      are tonically activated by a glutamate projection from prefrontal cortex (PCP
      blocks this source of activation) and are tonically inhibited by a dopaminergic
      projection from the ventral tegmental area (PCP augments this inhibition).

PMID- 8986013
TI  - Non-response to citalopram in depressive patients: pharmacokinetic and clinical
      consequences of a fluvoxamine augmentation.
AB  - The effect of comedication with fluvoxamine on the plasma concentrations of the
      enantiomers of citalopram and its metabolites in dextromethorphan/mephenytoin
      phenotyped patients pretreated with citalopram (CIT) was studied: seven female
      patients (45.1 +/- 13.9 years) suffering from a major depressive episode [ICD-10:
      F32.2 (n = 3 patients), F33.2 (n = 2), F32.10 (n = 1) or F32.11 (n = 1)], who
      were non-responders to a 3-week treatment with 40 mg/day CIT (From day-21 to day
      0) (day 0: MADRS score > or = 12), were co-medicated for another 3 weeks with
      fluvoxamine (50 mg/day from day 1-7, 100 mg/day from day 14-21). All patients
      were extensive metabolizers of mephenytoin (CYP2C19) and dextromethorphan
      (CYP2D6), except one patient, who had a genetic deficiency of CYP2D6. There was a
      significant increase of the plasma concentrations of S- and R-citalopram from day
      0 (27 +/- 14 micrograms/l and 55 +/- 23 micrograms/l, respectively) to day 21 (83
      +/- 38 micrograms/l and 98 +/- 44 micrograms/l, respectively), after addition of
      fluvoxamine (P < 0.02, for each comparison), and the mean ratio S/R-citalopram
      increased from 0.48 to 0.84. S-Citalopram inhibits more potently 5-HT uptake than
      R-citalopram: therefore, fluvoxamine increases the pharmacologically more active
      S-citalopram with some stereoselectivity. According to a previous in vitro study,
      this pharmacokinetic interaction occurs on the level of CYP2C19, but also of
      CYP2D6 and CYP3A4 which, in contrast to CYP1A2, contribute to the N-demethylation
      of citalopram and which are stereoselectively inhibited by fluvoxamine. All but
      one patient showed clinical improvement by a decrease of the MADRS score by at
      least 50% and a final score < or = 13 (mean +/- SD: day 0:30.6 +/- 9.2; day
      21:11.0 +/- 6.5). Some patients showed minor symptoms, such as nausea and tremor,
      but the combined treatment was generally well tolerated.

PMID- 8986014
TI  - An oral self-administration model of nicotine preference in rats: effects of
      mecamylamine.
AB  - A new oral model of nicotine self-administration in rats has been described. The
      model utilizes a two-lever operant procedure with rats having a choice between
      nicotine and water reinforcement. Most (16 of 20) rats exhibited reliable
      preferences for nicotine solutions equal to or less than 32 micrograms/ml;
      preferences were inversely related to the concentration of nicotine. Mecamylamine
      (0.25-5.0 mg/kg), a nicotinic antagonist, reduced preferences for a low nicotine
      concentration (4 micrograms/ml) and enhanced preferences for a high nicotine
      concentration (32 micrograms/ml). The relationship of nicotine concentration to
      nicotine preference appeared to be consistent with previous reports of nicotine
      self-administration using the intravenous route in rats as well as the
      respiratory route (i.e., smoking) in humans. The mecamylamine-induced changes in
      nicotine preference were consistent with its nicotinic antagonist action as well
      as with effects of mecamylamine reported in humans. This model should be useful
      in the preclinical assessment of new agents as potential therapies in smoking
      cessation programs.

PMID- 8986016
TI  - [Method for analyzing urinary organic solvents by solid-phase microextraction
      (SPME) for biological monitoring of exposure to these solvents].

PMID- 8986015
TI  - [The analysis of peripheral blood lymphocytes of patients with silicosis and
      effects of silica in vitro].
AB  - It is well known that patients with silicosis are frequently associated with
      hyperglobulinemia, RA or PSS. It is also suggested that silica can drive and
      activated the immune system. In this study, we intended to measure the percentage
      of CD4+CD45RA+ cells in the peripheral blood of patients with silicosis and to
      investigate whether silica can actually activate human lymphocytes in vitro or
      not. Peripheral blood from 45 patients with silicosis was stained with OKT4 and
      2H4 monoclonal antibodies, and measured by FACS analysis at 1st day and also
      checked similarly after 6 days-incubation without patients' sera. The
      intracellular Ca++ level was also checked after incubation with the normal human
      lymphocytes with silica by FACS analysis, using Fluo3-AM. CD4+CD45RA+ T cells
      decreased significantly in number. One to 5 minutes after the incubation with
      silica, intracellular Ca++ level increased markedly, which means the activation
      of lymphocytes in vitro. These results revealed that silica can activate human
      lymphocytes in vitro, but the role in vivo remains to be clarified.

PMID- 8986017
TI  - [Effect of low- and high-molecular components contained in human plasma on
      superoxide dismutase activity].

PMID- 8986018
TI  - [A questionnaire study on health administration in small enterprises in a rural
      region].
AB  - A questionnaire study on the health administration of industrial workers was
      performed on 230 enterprises in city A in a rural region. Responding subjects
      numbered 140 and the response rate was 60.9%. Subjects by scale were: 16% with
      more than 50 workers, 48% with from 10 to 49 workers and 36% with less than 10
      workers, and the proportions by industry were: 32% manufacturing, 22% wholesale
      retail trade and 14% construction. The subject proportions classified according
      to the health insurance scheme were: 59% government-managed health insurance, 15%
      national health insurance and 11% society-managed health insurance. The rate of
      periodic health examination was 100% in enterprises with more than 50 workers,
      67.2% in those with from 10 to 49 workers and 51.0% in those with less than 10
      workers. The main reasons why then did not receive health examinations were: 40%
      had no time available to conduct examinations, 21% believed such examinations
      were not necessary, and 19% did not know of such an examination system. They
      encountered some difficulties in promoting health; for example, the advanced age
      of workers, and no time or money to spare for health administration. They desired
      provision of facilities close at hand for health examination, health consultation
      and health information. The results of this study show the difficulty of
      promoting health administration in small scale enterprises and also that it is
      difficult to obtain accurate information on actUal conditions including health
      administration in small enterprises.

PMID- 8986020
TI  - A solution and solid state 15N NMR study of hydrogen bonding in a Schiffs base.
AB  - The 15N results reveal a difference in the extent of intramolecular hydrogen bond
      formation exhibited by the Schiffs base, compound 2, in solution and the solid
      state. Comparison of the 15N shielding changes observed, with those arising from
      protonation, provides the basis for a quantitative estimate of the strength of
      the hydrogen bonds formed.

PMID- 8986019
TI  - An 15N NMR study of the protonation of two di-(alpha-pyridyl) compounds in
      solutions and the solid state.
AB  - 15N NMR data are reported for two Di-(alpha-pyridyl) derivatives in various
      stages of protonation. A combination of 15N NMR measurements taken, on a number
      of solutions, and on the solid state provide a quantitative overall view of the
      progress of protonation of these compounds. 15N shieldings, J(15N-1H) and 2J (15N
      1H) interactions all provide information indicative of unsymmetrical
      monoprotonation in the solid state and producing both the monoprotonated [N-H-N]+
      structure and the diprotonated structure in the presence of an excess of TFA.

PMID- 8986021
TI  - Analysis of spin-diffusion measurements by iterative optimisation of numerical
      models.
AB  - This work shows how information from a number of solid-state 1H NMR experiments
      can be combined in a numerical model of a heterogeneous polymer system, which can
      then be iteratively optimised by varying a small number of parameters to fully
      represent the spin-diffusion and relaxation behaviour of the system. In this way
      useful information can be obtained not only about the size of the heterogeneities
      present, but also about the intrinsic relaxation behavior of the different
      regions.

PMID- 8986022
TI  - Characterisation of sodium cations in dehydrated zeolite NaX by 23Na NMR
      spectroscopy.
AB  - 23Na MAS, 2D nutation MAS, and DOR NMR spectroscopy has been applied to
      characterise the location of sodium cations in dehydrated zeolite NaX (Si/Al =
      1.23). The 23Na MAS NMR spectra recorded at three different magnetic field
      strengths were decomposed by computer simulation into five lines, which were
      attributed to five crystallographically distinct cation sites known from X-ray
      diffraction studies. The assignments of the lines follow from electric field
      gradient calculations at the 23Na nuclei applying a simple point charge model
      based on crystal structure data. A weak Gaussian line at low field (delta iso = 
      6 ppm) is assigned to sodium cations at site I, two broad quadrupole patterns at
      the high-field side of the spectra are attributed to site I' (delta iso = -19
      ppm, QCC = 5.2 MHz, eta = 0) and site II cations (delta iso = -15 ppm, QCC = 4.6
      MHz, eta = 0), and two quadrupolar lines dominating the central region of the
      spectra originate from Na+ at two different III' sites (delta iso = -13 and -29
      ppm, QCC = 2.6 and 1.6 MHz, eta = 0.7 and 0.9, respectively). Na+ ions located on
      a second I' site could be identified from the DOR NMR spectra. The line
      assignment is further corroborated by the reasonable agreement of the site
      occupancies estimated from the line intensities with those determined by X-ray
      diffraction. In addition, sodium site populations of five dehydrated zeolites NaX
      and NaY with Si/Al ratios between 1.09 and 4.0 were derived from the 23Na MAS NMR
      spectra.

PMID- 8986023
TI  - Anisotropy of the proton T1 and the low-field relaxation in NH4 ClO4 below 20K.
AB  - The spin-lattice relaxation of protons in NH4ClO4 at low temperatures has been
      studied theoretically and experimentally. The NH4 librational tunneling
      determines the spin-librational wavefunctions, which are derived first. The
      dominant transition rates related to the magnetic dipolar interaction between the
      NH4 protons are then obtained. They reproduce well the angular dependence of the
      proton relaxation time. When all the transition rates are taken into account,
      both the temperature and frequency dependence of the relaxation rate agree with
      our experimental data for a powder sample. Reasons for the non-exponential
      relaxation are discussed. Apart from the angular dependence of the relaxation
      rate, they include the tunnel frequency distribution, the coupling to the tunnel
      reservoir and the effect of deuterons in their natural concentration.

PMID- 8986024
TI  - 13C CP/MAS NMR of a 13C-2H residual dipolar coupled pair.
AB  - When a spin-1/2 nucleus is dipolar coupled to a spin-1 nucleus, the spectrum of
      the spin-1/2 nucleus can be split into an asymmetric doublet in magic-angle
      spinning experiments. When the spin-1/2 nucleus is 13C and the spin-1 nucleus is
      2H there is also the possibility of this splitting being modified by the indirect
      (J) coupling. 13C-2H residual dipolar couplings are seen because of the large
      full dipolar coupling of the nucleus pair. However, this has implications on the
      spinning speed used in the CP/MAS NMR experiment and the intensities of the
      isotropic 13C dipolar coupled to 2H. The calculation of side band intensities for
      slow spinning when the dipolar, quadrupolar and chemical shift tensors are
      axially symmetric and coaxial is discussed.

PMID- 8986025
TI  - Squaric acid as an internal standard for temperature measurements in 13C MAS NMR.
AB  - Squaric acid (3,4-dihydroxy-3-cyclobutene-1,2-dione) is suggested as an internal
      standard for temperature measurements in 13C MAS NMR studies in the temperature
      range from 373 K to 520 K. Compared to previously utilized standards, squaric
      acid has several important advantages, such as fast kinetics of the phase
      transition, higher temperature range for 13C studies, and an almost constant
      sample volume through the transition temperature range. Thus, we found squaric
      acid to be suitable for the probe calibration with the reference temperature at
      373.2 K. Moreover, upon partial deuteration the reference temperature can be
      gradually increased to 520 K. Additionally, the described procedure makes it
      possible to quantitatively estimate the temperature gradient across the sample.
      We also discuss the effect of spinning related stress on the temperature
      measurement technique and how this effect could be minimized.

PMID- 8986026
TI  - Solid state NMR study on the conformation and mobility of n-octadecyl chains in a
      silane coupling agent attached to the surface of colloidal silica.
AB  - The surface of colloidal silica of 22 nm and 100 nm in diameter has been modified
      with a silane coupling agent, n-octadecyltriethoxysilane. The solid state 13C NMR
      spectrum shows surprisingly that the covalently bonded n-octadecyl chains on the
      silica surface adopt largely extended all-trans conformation. By increasing the
      temperature to 70 degrees C, the trans conformations observed at room temperature
      can be converted to a disordered state in which the trans and gauche conformers
      are under rapid exchange (mobile disorder). On cooling to ambient temperature,
      the trans conformation cannot be recovered and a distribution of chain
      conformations can be observed, indicating that the disorder has been frozen-in
      (rigid disorder). Subsequent treatment of the surface modified silica with a
      second reagent, such as trimethylsilychloride or ethanol reacts with the
      remaining surface hydroxy groups and causes the n-octadecyl chains to collapse to
      the mobile, disordered state. The 13C spin-lattice relaxation times for carbon
      atoms in the all-trans conformation are longer than those in the mobile,
      disordered chains, indicating that there is more restriction of motion in the
      trans octadecyl chains. Instead of crystallization of the octadecyl chains on the
      silica surface, other factors, such as static interactions, might be responsible
      for the existence of trans conformation in the octadecyl chains.

PMID- 8986027
TI  - A 119Sn solid-state nuclear magnetic resonance study of crystalline tin
      sulphides.
AB  - Non-spinning and magic angle spinning (MAS) 119Sn nuclear magnetic resonance
      (NMR) spectra of the binary tin sulphides SnS and SnS2 as well as of a number of
      stoichiometric compounds from the ternary system Na2S-SnS2 have been recorded.
      The isotropic chemical shift was found to cover a range of more than 800 ppm and
      allows us to distinguish between different coordination numbers of Sn(IV) present
      in tin sulphides. Moreover, the chemical shift anisotropy (c.s.a.) is shown to be
      a sensitive indicator for deformations in the coordination sphere of the tin atom
      and can be discussed with respect to the known structures of the compounds.

PMID- 8986028
TI  - Couples and reproductive health: a review of couple studies.
AB  - Traditionally, fertility and family planning research and programs have focused
      on women. With the expansion of the field to include reproductive health
      following the 1994 International Conference on Population in Cairo, the more
      appropriate focus for most reproductive health components appears to be the
      sexually active couple. This review of studies of couples and reproductive health
      outcomes examines reports of objective reproductive events, of attitudes and
      reproductive intentions, of the effect of each partner's attitudes and
      intentions, of reproductive outcomes, and of the effectiveness of interventions
      that target couples compared with those that target one partner or the other. For
      couples' statements about reproductive events, studies throughout the world
      typically show identical reports less than 90 percent of the time. Concordance
      between partners on subjective matters is in the range of 60 to 70 percent. Data
      based on reports of reproductive intentions from both partners have been shown to
      lead to better predictions of behavior than have data from only one partner.
      Finally, reproductive health interventions that target couples are found to be
      more effective than those directed to only one sex. The evidence clearly
      justifies a focus on couples.

PMID- 8986029
TI  - Reproductive preferences and fertility trends in post-transition Thailand.
AB  - Two large national surveys in 1988 and 1933 provide new evidence on trends in
      family-size preferences in Thailand at a time when the Thai fertility transition
      is reaching its conclusion. Although the average preferred number of children has
      continued to decline, a resistant lower bound of two children is found for the
      vast majority of respondents, stemming, apparently, from a pervasive, although
      not inflexible, desire to have one child of each sex. Moreover, new evidence from
      birth-registration data indicates that the decline in the total fertility rate
      appears to have leveled off at about replacement level. These findings challenge
      the view that fertility in Thailand will continue to fall well below replacement
      level, and contradict recently expressed alarmist predictions of population
      decline in the foreseeable future.

PMID- 8986030
TI  - A community-based investigation of avoidable factors for maternal mortality in
      Zimbabwe.
AB  - A community-based investigation of maternal deaths was undertaken in a rural
      province (Masvingo) and an urban area (Harare) of Zimbabwe in order to assess
      their preventability. Avoidable factors were identified in 90 percent of the 105
      rural deaths and 85 percent of 61 urban deaths. Delay in seeking treatment
      contributed to 32 percent and 28 percent of rural and urban deaths, respectively.
      Lack of transportation delayed or prevented access to healthy facilities in the
      rural area, a major problem in 28 percent of the cases studied. Suboptimal clinic
      and hospital management was identified in 67 percent and 70 percent of rural and
      urban deaths, respectively. Lack of appropriately trained personnel contributed
      to suboptimal care. In both settings, the severity of patients' conditions was
      frequently unrecognized, leading to delays in treatment and referral, and
      inadequate treatment. Appropriate community and health-service interventions to
      reduce maternal mortality are discussed.

PMID- 8986032
TI  - Lessons from the Dutch abortion experience.

PMID- 8986031
TI  - Women's position and family planning in Egypt.
AB  - In this report, data from the 1988 Egypt Demographic and Health Survey are used
      to address some of the most frequently raised questions about the relationship
      between gender inequality and reproductive behavior. The findings from binomial
      and multinomial logit models show that while the relationship between women's
      position and fertility control in Egypt is complex, some clear, broad patterns
      exist that have important theoretical and policy implications. First, although
      women's status in Egypt is clearly multidimensional, the reproductive aspect of
      women's position has a strong connection with the nonreproductive dimensions.
      Second, the case of the continued use of education and employment as proxies of
      women's position, especially in relationship to fertility control, is
      considerably discredited by the results. Finally, the findings indicate that
      Egyptian culture supports gender equality in the form of interaction and
      negotiation rather than women's autonomy.

PMID- 8986033
TI  - Morocco 1995: results from the Demographic and Health Survey.

PMID- 8986034
TI  - Therapy of primary biliary cirrhosis with p-tolylmethylcarbinol nicotinic acid
      ester in combination with alpha-naphthylacetic acid.
AB  - OBJECTIVE: To assess the effect of choleretic treatment with p
      tolylmethylcarbinol nicotinic acid ester and alpha-naphthylacetic acid (Galle
      Donau) on laboratory parameters of cholestasis, lipids, immunologic activity and
      on clinical signs in primary biliary cirrhosis patients. DESIGN: Prospective, non
      randomized case control study; retrospective evaluation of pre-treatment period,
      evaluation of six months of treatment, open study after six month of treatment
      with evaluation of patients further treated and patients who discontinued
      treatment. PATIENTS AND METHODS: Twelve consecutive patients with proven primary
      biliary cirrhosis, all female. Patients were to take six to nine capsules of
      Galle-Donau, containing 37.5 mg p-tolymethylcarbinol nicotinic acid ester and 75
      mg alpha-naphthylacetic acid (5 mg per kg of body weight and 10 mg), daily in
      three doses, together with meals. Six patients discontinued treatment with Galle
      Donau after six months and were followed up further. RESULTS: After six months of
      Galle-Donau treatment the average alkaline phosphatase level dropped from 670.8
      IU/ml to 577.1 IU/ml; the levels of total bilirubin (1.46 vs. 1.15 mg/100 ml) and
      unconjugated bilirubin (0.82 vs. 0.63 mg/100 ml) also decreased under therapy.
      This drop was not significant, while the decrease in triglycerides (149.2 vs.
      103.1 mg/100 ml) reached statistical significance. During further treatment for
      up to two years patients showed no significant change in triglycerides,
      cholesterol or alkaline phosphatase. y-Glutamyl transpeptidase was not changed by
      treatment. Discontinuance of treatment resulted in significant increases in
      alkaline phosphatase and y-glutamyl transpeptidase, as well as in bilirubin
      levels. Triglyceride values also rose significantly when treatment was stopped,
      while the increase in cholesterol did not reach statistical significance. No
      influence of Galle-Donau treatment was found on IgM level. Pruritus (five
      patients) and Sicca symptoms (six patients) resolved within the treatment period
      in all but one patient (Sicca symptoms) who did not take the medication
      regularly. In the group of patients who discontinued therapy pruritus returned in
      both patients who had complained of it before therapy. Sicca symptoms returned in
      one out of three patients. CONCLUSION: Treatment with p-tolylmethylcarbinol
      nicotinic acid ester and alpha-naphthylacetic acid leads to relief of symptoms
      and ameliorates biochemical parameters of cholestasis may, therefore, be of value
      for PBC therapy.

PMID- 8986036
TI  - Lack of correlation between prostate-specific antigen density and prostatic
      shrinkage in response to finasteride therapy.
AB  - We attempted to correlate prostate volume reduction in response to finasteride
      treatment with initial prostate-specific antigen (PSA) levels and PSA density in
      men with symptomatic benign prostatic hyperplasia (BPH). The average reductions
      in prostatic volume (transrectal ultrasonography) were 27% and 34% after 6 and 12
      months of finasteride therapy, respectively. Serum PSA levels decreased by 45% (6
      months) and 50% (12 months). There was a positive correlation between initial
      serum PSA values and initial prostate volumes (r = 0.57, P < 0.001). There was no
      correlation, however, between the initial serum PSA or PSA-density values and
      prostate volume reduction. These data indicate that initial serum PSA and PSA
      density values are not predictive of the response to finasteride therapy in terms
      of prostate size reduction.

PMID- 8986035
TI  - The role of paclitaxel in chemosensitive urological malignancies: current
      strategies in bladder cancer and testicular germ-cell tumors.
AB  - Recent results demonstrate an emerging role for paclitaxel in patients with
      urothelial-tract cancer and in patients with testicular cancer. Yielding response
      rates in the range of 40-50% as a single agent, paclitaxel is one of the most
      active drugs in metastatic bladder cancer. Ongoing trials of paclitaxel
      combination chemotherapy with cisplatin or cisplatin and ifosfamide demonstrate
      substantial objective remission rates above 70% and, in addition, a high range of
      complete responses. Thus, paclitaxel appears to be an important drug when used as
      part of first-line combination chemotherapy for metastatic bladder cancer.
      Ongoing clinical trials focus on the combination of paclitaxel with cisplatin,
      ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxel administration
      has been demonstrated to be easily applicable to patients with reduced renal
      function, requiring no dose reduction and producing no increase in toxicity.
      Future strategies will have to compare the most active paclitaxel combination
      regimen with first-line MVAC (methotrexate, vinblastine, adriamycin, cisplatin)
      chemotherapy. Finally, the role of paclitaxel combination regimens needs to be
      explored in the adjuvant and neoadjuvant setting in patients with bladder cancer.
      In testicular cancer, paclitaxel has initially been tested in patients with
      cisplatin-refractory disease. Among 4 consecutive trials involving a total of 83
      patients a response rate of 26% has been observed using dose schedules varying
      from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m2. The major
      toxicities of paclitaxel include neutropenia, neurotoxicity, and fatigue
      syndrome. Currently, combinations of paclitaxel with cisplatin +/- ifosfamide are
      used as first- or second-line salvage therapy in patients with relapsed
      metastatic testicular cancer. The German Testicular Cancer Study Group uses a
      paclitaxel (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage
      treatment. Following the TIP regimen and the application of granulocyte colony
      stimulating factor (G-CSF), peripheral blood stem cells (PBSC) are harvested and
      the patients subsequently receive high-dose chemotherapy with PBSC rescue. Since
      only a few drugs have demonstrated substantial activity in cisplatin-refractory
      disease, paclitaxel will be used in early salvage strategies and, possibly, as
      first-line chemotherapy as a part of platinum-based combination regimens in
      patients with testicular cancer. Further trials confirming the important role of
      paclitaxel in this highly curable malignancy and a thorough investigation of its
      acute and long-term toxicity will be the future tasks.

PMID- 8986037
TI  - Risk of progression and dying of clinically localized prostate cancer in Japan.
AB  - Study was made of the conservative management of 107 men with clinically
      localized prostate cancer. Distant metastasis developed more frequently in
      patients with poorly differentiated tumors than in those with well- and
      moderately differentiated counterparts (P < 0.01). Poorly differentiated
      histology was strongly associated with cancer-specific death (P < 0.01). The
      progression-free and cancer-specific survival of patients with stage T1a disease
      was significantly better than that of patients with stages T1b, T2a-b, and T2c
      tumors (P < 0.05). Available data clearly demonstrate that prostate cancer is a
      progressive disease when managed conservatively. Long-term follow-up data
      indicate the natural history of prostate cancer not to differ significantly
      according to race, despite noteworthy differences in prevalence and mortality.
      Patients with localized prostate cancer would be candidates for expectant therapy
      if they had lower-grade tumors and a life expectancy of 10 years or less. For
      patients with a 10-year or greater life expectancy and any grade of disease
      definitive therapy should be applicable.

PMID- 8986038
TI  - Continent small-intestine reservoir construction: a tapered intussusceptum
      promotes sustained continence.
AB  - Developed for the study of dialysis in the continent jejunal reservoir (CJR), a
      novel, uncomplicated approach to achieve continence in construction of a small
      bowel reservoir is presented. We utilize a technique of constructing a continent
      nipple valve, which entails the reduction or tapering of the intussusceptum prior
      to invagination into the reservoir. We have thus far performed the procedure
      successfully in 21 dogs. All animals have achieved absolute continence.
      Complications have occurred in two animals, neither complication involving the
      nipple valve. Pressure-volume cytometry in nine animals demonstrates continence
      in the awake animal at pressures of up to 40 cm H2O (volumes being limited by
      animal discomfort due to reservoir distention). In postmortem studies, reservoir
      capacities of > 1000 ml and pressures of > 70 cm H2O have been attained without
      loss of continence or prolapse of the nipple valve. Continence is sustained even
      when the reservoir and nipple valve are subjected to high intraluminal pressures.
      Incorporating a tapered intussusceptum, the continent reservoir provides absolute
      continence without the use of cumbersome mesh fixation or lithotropic
      intraluminal staples.

PMID- 8986040
TI  - Long-term outcome of kidneys with initially poor drainage or no drainage
      following pyeloplasty.
AB  - Pyeloplasty for congenital ureteropelvic junction (UPJ) obstruction enjoys a 90
      95% success rate. Although treatment of the failed pyeloplasty has been addressed
      in the literature, management of the poorly draining or nondraining renal unit in
      the immediate postoperative period has not received any attention. For this
      purpose the medical records of 33 consecutive children (37 renal units) treated
      by dismembered pyeloplasty between 1986 and 1992 were reviewed. All of our
      pyeloplasties were stented and urine was diverted via a nephrostomy tube. All
      patients underwent a nephrostogram following stent removal 1 week
      postoperatively. These studies showed poor drainage, or no, across the newly
      reconstructed anastomosis in 7 of 37 renal units (19%). The ages of these 4 boys
      and 3 girls at the time of pyeloplasty ranged between 7 weeks and 5 years (mean
      22 months). In four patients, good drainage occurred without intervention by 2-4
      weeks postoperation. In two patients, percutaneous balloon dilation of the
      anastomosis via the intraoperatively placed nephrostomy tube was required at 3
      and 6 weeks, respectively. The remaining patient failed percutaneous dilation,
      necessitating a ureterocalycostomy at 9 weeks following pyeloplasty. The long
      term follow-up for the entire group of 33 children averaged 30 months and
      consisted of radionuclide diuresis renography in 84% of cases or intravenous
      pyelography in the remainder. All patients had excellent long-term outcomes as
      assessed by comparison of the postoperative studies with the baseline studies
      obtained preoperatively. Our results show that kidneys with initially poor
      drainage, or even no drainage, across the newly reconstructed anastomosis
      following pyeloplasty can be salvaged with an excellent long-term outcome
      comparable with that of the group with initially good drainage. In addition,
      intervention was necessary in only 43% of renal units with initial compromise and
      was facilitated by the intraoperatively placed nephrostomy tube. We recommend
      that percutaneous dilation be done at between 4 and 6 weeks postpyeloplasty, as
      the waiting period was long enough to allow for spontaneous improvement without
      precluding a successful outcome if drainage failed to occur. Ureterocalycostomy
      was rarely necessary.

PMID- 8986041
TI  - A new approach to the closure of cloacal exstrophy.
AB  - Cloacal exstrophy patients are often difficult to reconstruct. Urinary continence
      is usually achievable only with a catheterizable stoma of some type. Since
      cloacal exstrophy is usually associated with omphalocele or gastroschisis, one
      stage closure of the abdominal wall defect is frequently impossible. We prefer to
      incorporate the exstrophic large bowel, which separates the hemibladders, into
      the closed bladder as a sort of "natural" augmentation to maximize its volume for
      use as a continent reservoir. If a silastic "silo" or synthetic mesh is required
      to close the abdominal wall, excessive scarring occurs and later creation of a
      continent stoma is usually difficult and time-consuming. In all but those with
      the smallest abdominal wall defects we recommend that the omphalocele and upper
      abdominal wall be repaired first, replacing the evicted gut into the peritoneal
      cavity. During nutritional stabilization a tissue expander is placed under the
      superficial musculature of the chest wall. The flap is enlarged by gradual
      inflation of the tissue expander until it fills the abdominal wall defect left by
      subsequent closure of the cloacal exstrophy. The flap is then rotated inferiorly
      with blood supply intact at the time of bladder closure to make good the
      remaining abdominal wall defect. This flap improves the appearance of the
      abdominal wall and reduces scarring. Thus, this approach has the possibility of
      making subsequent operations to provide continence shorter, simpler, and more
      successful in most infants with cloacal exstrophy.

PMID- 8986039
TI  - The renal paracrine peptide system--possible urologic implications of urodilatin.
AB  - Cardiodilatin/atrial natriuretic peptide (CDD/ ANP) is a hormone system of great
      clinical importance. The prohormone CDD/ANP-1-126 is a peptide synthesized in the
      heart and cleaved during exocytosis into the circulating form CDD/ANP-99-126.
      Urodilatin (CDD/ ANP-95-126) is a homologue natriuretic peptide that differs from
      CDD/ANP-99-126 by four amino acids. Whereas CDD/ANP-99-126 circulates in blood
      plasma and is not excreted into the urine, urodilatin is detected only in urine.
      Urodilatin exerts its renal effects in a paracrine fashion. After its secretion
      from cells in the distal tubule, it interacts with luminally located receptors in
      the collecting duct, resulting in increased diuresis and natriuresis. Results
      suggest that urodilatin plays an important role in the physiologic regulation of
      fluid-balance and sodium homeostasis. Pharmacology studies reveal significant
      differences when urodilatin and CDD/ANP-99-126 are given intravenously, showing
      that stronger diuresis and natriuresis are induced by urodilatin as compared with
      those induced by CDD/ANP-99-126. Clinical studies indicate the prophylactic and
      therapeutic effect of urodilatin in patients suffering from acute renal failure
      following heart and liver transplantation. A significant reduction in
      requirements for hemodialysis/hemofiltration can be achieved using urodilatin.
      Postobstructive diuresis and natriuresis is probably due to a defective urinary
      concentrating mechanism and is usually resistant to treatment with antidiuretic
      hormone. The distal tubule and collecting duct have often been considered to be
      the site of altered sodium and water excretion following relief of obstruction.
      Since circulating CDD/ANP-99-126 levels are markedly elevated during obstruction
      and decrease upon relief of the obstruction, natriuretic peptides may play an
      important role in this clinical feature. On the basis of recent findings
      attributing an important role in sodium homeostasis to urodilatin in contrast to
      CDD/ANP-99-126, future studies have to clarify whether urodilatin, not CDD/ANP-99
      126, might be responsible for the altered renal sodium excretion observed in
      postobstructive diuresis. In the past decade a considerable amount of research
      has led to the identification and characterization of hormones of the natriuretic
      peptide family [13]. These peptides are involved in the regulation of salt and
      water homeostasis. The prototype of the natriuretic hormones is
      cardiodilatin/atrial natriuretic peptide (CDD/ANP), or A-type natriuretic
      peptide. CDD/ANP is primarily produced in the heart [6]. It is synthesized as a
      precursor molecule, CDD/ ANP-1-126, in specific granules in atrial myoendocrine
      cells [15]. The prohormone, upon appropriate stimuli for release, is cleaved into
      the C-terminus CDD/ANP-99-126 and excreted into the circulation via exocytosis
      [16]. Further members of the natriuretic peptide family are brain natriuretic
      peptide (BNP, or B-type natriuretic peptide) [45] and C-type natriuretic peptide
      (CNP) [46]. All the members of this family share many common features, including
      tissue distribution of gene expression, biosynthetic pathways, and pharmacologic
      effects in target organs [13,26]. The main biologic effects of these hormones are
      natriuresis, diuresis, and vasodilation [5, 6, 14, 22], but these vary among the
      individual peptides. Natriuretic effects such as increased glomerular filtration,
      inhibition of aldosterone production, and secretion result from direct inhibition
      of sodium absorption in the collecting duct. Urodilatin (INN: Ularitide) is a
      member of the natriuretic peptide family, discovered in 1988 by Schulz-Knappe et
      al. [43]. This hormone is presumably synthesized in the kidney and exerts
      potential paracrine renal effects [17]. Results of clinical phase I-II trials
      suggest a potent therapeutic effect of urodilatin in the treatment of acute renal
      failure in patients following organ transplantation [4, 27, 33].

PMID- 8986043
TI  - Electrovasogram in patients with obstructive azoospermia and absent vas deferens.
AB  - The electric activity of the vas deferens (electrovasogram, EVG) was studied in
      22 patients with obstructive azoospermia (OA), in 9 patients with bilaterally
      absent vasa deferentia, in 10 patients who had undergone epididymovasostomy for
      OA, and in 12 healthy volunteers (controls). Two electrodes were applied to the
      posterior aspect of the upper scrotum. EVG in normal subjects showed pacesetter
      potentials (PPs) that had the same frequency, amplitude, and velocity of
      conduction from both electrodes and were consistent in the individual subject on
      all test days. The PPs were followed randomly by action potentials (APs). The EVG
      in OA exhibited "bradyvasa," i.e., diminished PP frequency, amplitude, and
      velocity, in 14 patients and a silent EVG in 8. Eight of the ten patients in whom
      azoospermia persisted after epididymovasostomy had a silent EVG. The remaining
      two patients, whose semen character had normalized after epididymovasostomy,
      revealed a normal EVG. A "silent" EVG was recorded for the nine patients with
      absent vasa deferentia. The electric activity is believed to be responsible for
      vasal motility. The bradyvasa or silent EVG encountered in OA might be
      attributable to the arrested function of the vas deferens and resultant vasal
      inertia. The latter may persist after epididymovasostomy and be responsible for
      the failure of the semen to normalize, as occurred in eight patients. In
      conclusion, EVG is a simple, easy, noninvasive, and nonradiologic technique that
      might be used as a diagnostic tool in the investigation of vas deferens disorders
      and infertility.

PMID- 8986042
TI  - Comparative studies on urethral function.
AB  - Urethral pressure profiles (in vivo), opening pressures, and flow rates at
      opening pressure (in vitro) were determined for female, male, pregnant,
      ovariectomized (OVX), OVX and then estrogen-treated, and OVX and then
      progesterone-treated rabbits. Using the isolated whole-urethra preparation, we
      determined the opening pressures and flow rates as well as the effects of 250
      microM phenylephrine, 250 microM bethanechol, and 120 mM KCl on the urethral
      opening pressure and flow rate. The results demonstrated that (1) the urethral
      pressure profiles were similar for male and female rabbits, (2) ovariectomy and
      pregnancy decreased the urethral pressure profiles, (3) estrogen therapy
      partially reversed the effect of ovariectomy on the urethra, and (4) progesterone
      therapy had little effect on the urethral pressure profile. With regard to
      opening pressure and flow, (1) flow at opening pressure was lower in the male
      than in the female; (2) the opening pressure was increased by ovariectomy; (3)
      phenylephrine and KCl stimulated a greater response in the male than in the
      female, whereas the response to bethanechol was significantly lower in the male
      than in the female; (4) the male had the greatest resistance to flow among all
      the groups; and (5) ovariectomy increased the resistance to flow and estrogen
      treatment reversed the effect of ovariectomy. In conclusion, ovariectomy had
      significant effects on urethral function that were reversed by estrogen therapy
      but not by progesterone therapy.

PMID- 8986044
TI  - Adenocarcinoma of the rete testis.
AB  - Adenocarcinoma of the rete testis is a rare tumor. Histologic diagnosis is
      difficult, and in the past the tumor may have been incorrectly identified in a
      number of cases, leading to misleading information on the nature and behavior of
      this neoplasm. We present the case of a 39-year-old man with a long history of a
      small left hydrocele, who was lost to follow-up and presented again 2 years later
      with testicular discomfort. Sonographic findings were consistent with a
      testicular tumor. Histology confirmed low-grade adenocarcinoma of the rete
      testis, the first reported tumor of this grade. Previously reported cases of rete
      testis carcinoma are reviewed.

PMID- 8986045
TI  - Development of hearing and vocalization in a marsupial, the Northern Quoll,
      Dasyurus hallucatus.
AB  - The development of hearing was studied in the Northern Quoll, a nocturnal
      marsupial carnivore whose young are born into a pouch in an immature state after
      about 21 days in utero. Startle responses to noise bursts of 105 dB sound
      pressure level first appeared at 60 days after arrival in the pouch, but only to
      occasional stimuli; forelimb rather than whole body twitches were evoked. The
      latter were elicited regularly at 67 days onward. Auditory brainstem response
      (ABR) audiograms were measured during the period when startle responses first
      appeared. At 68 days responses were elicited between 1 and 16 kHz with thresholds
      in excess of 55 dB. At 81-88 days responses occurred over the adult range at
      lower thresholds than observed in the adult. The waveform of the ABR increased in
      complexity and decreased in latency during development. Pouch-young emitted
      acoustically well-defined isolation cells when separated from their mothers.
      Fourier analysis of these calls revealed peak energy at 8-11 kHz irrespective of
      the sex of the pouch-young. The isolation call first became evident at about 35
      days, when the young were deliberately removed from the nipple, and ceased being
      emitted beyond about 80 days, some 5 or so days after the eyes open, when the
      young leave the pouch for substantial amounts of time. The spectrum of the call
      was similar at all ages within this 45 day period, and its peak frequency
      correlated closely with the best frequency in the adult quoll's ABR audiogram. At
      approximately 80 days of age the calls developed major low frequency components,
      similar to those measured in adult vocalizations, and the contributions of
      frequencies between 8-11 kHz waned in importance. The results indicate that the
      onset of hearing in quolls occurs at a relatively early time in the course of
      their development, but prior to this time the pouch-young emit characteristic
      isolation calls easily detectable by the mother.

PMID- 8986046
TI  - Partial purification and characterization of serum embryotrophic factor required
      for early postimplantation growth of rat embryos in culture.
AB  - Serum embryotrophic factor (SEF) required for the growth of cultured
      postimplantation rat embryos was partially purified from rat serum. Rabbit serum
      was used as a basal medium for the embryo culture, and embryotrophic activity was
      measured as embryonic protein increase. For partial purification of SEF, the rat
      serum globulin fraction obtained by ultracentrifugation and (NH4)2SO4
      precipitation was fractionated by gel filtration, diethylaminoethyl ion-exchange
      chromatography, and hydroxyapatite chromatography. Partially purified SEF was
      characterized by stability tests and affinity chromatography. SEF was inactivated
      by heat, acid, dithiothreitol reduction, or trypsin digestion. SEF bound to
      concanavalin A but not to heparin. These results indicated that SEF was an acid
      labile acidic glycoprotein with disulphide bonds and no affinity for heparin. The
      M(r) of SEF was estimated to be about 180 x 10(3) by gel filtration. The specific
      activity (U/g protein) was increased about 25-fold with 9.4% recovery by the
      partial purification, when 1 U of SEF was defined as the amount giving 50%
      embryonic protein increase. By polyacrylamide gel electrophoresis, a protein most
      likely to be SEF was identified as a heterodimer composed of subunits of M(r) 116
      x 10(3) and 62 x 10(3) linked by disulphide bonds, and was shown to be contained
      in the medium at micromolar concentrations. SEF appeared to be distinct from
      known protein embryotrophic factors, growth factors, or cytokines.

PMID- 8986047
TI  - Atrial natriuretic peptide, bradykinin, and angiotensin II-like immunoreactivity
      in the harderian gland of the terrapin Pseudemys scripta: response to osmotic
      stress.
AB  - The Harderian gland of the terrapin Pseudemys scripta has four types of acinar
      cells. Type IV cells are very similar to the salt secreting cells of the salt
      secretory glands of various marine vertebrates. The presence and localization of
      the Ile5-Angiotensin II, Atrial Natriuretic Peptide, and Bradykinin has been
      investigated by immunohistochemical methods. Immunoreactivity is confined to the
      type IV cells. Changes in the environmental salinity resulted in different
      patterns in the immunoreactivity especially after incubation with Ab-Angiotensin
      II and Ab-Atrial Natriuretic Peptide. Immunoreactive Angiotensin II cells are
      more numerous in animals maintained in distilled water, when reabsorption of
      sodium is needed. In contrast, immunoreactive Angiotensin II cells are very few
      in animals maintained in seawater. On the contrary, the number of immunoreactive
      cells for Atrial Natriuretic Peptide is high in seawater maintained animals, and
      weaker in animals in distilled water. The type IV cell may be considered a
      candidate for ion regulation in the terrapin Harderian gland.

PMID- 8986048
TI  - Complete obstruction of a naso-endotracheal tube. A case report.
AB  - A case of a complete obstruction of a naso-endotracheal tube is presented. The
      obstruction was caused by a fractured turbinate during the intubation.

PMID- 8986049
TI  - Noma: clinical and evolutive aspect.
AB  - Noma is a gangrenous stomatitis affecting children from developing countries. It
      may leave dreadful mutilations around the mouth, leading to esthetic disabling
      sequels and permanent trismus. Iconography of the acute stage and of sequels is
      presented in this paper, and pathogenesis of the disease is discussed.

PMID- 8986050
TI  - Proliferating cell nuclear antigen (PCNA) as a marker of dysplasia in oral
      mucosa.
AB  - The development of head and neck cancer has been proposed to be a multistep
      process, with accumulation of genetic and phenotypic alterations resulting from
      carcinogen exposure. Proliferating cell nuclear antigen (PCNA), also called
      cyclin, is a 36-KD auxiliary protein of DNA polymerase-delta, that has been found
      to be a useful marker in immunocytochemical studies of cell proliferation because
      its expression correlates with the proliferative state of the cell. PCNA
      expression was analyzed in 10 samples of normal mucosa, 23 benign oral lesions
      (18 hyperplasia and 5 oral lichen plani), 10 oral lesions with epithelial
      dysplasia, and 10 dysplastic epithelia adjacent to tumors. Immunocytochemical
      stained sections were scored for the presence or absence of suprabasal PCNA
      positivity regardless of location. The results indicate that the PCNA expression
      in the suprabasal layers increased with the degree of epithelia dysplasia and in
      the samples of histological dysplastic epithelium adjacent to the tumors, while
      the percentage of suprabasal PCNA expression was insignificant in the samples of
      normal oral mucosa and benign oral lesions. The authors conclude that suprabasal
      PCNA expression could be a marker of dysplasia in oral mucosa, indicating a
      special proliferative cellular state in those lesions.

PMID- 8986051
TI  - Indications for compensatory extractions in orthodontic space closure in the
      frontal segments.
AB  - This follow-up study presents patients who underwent orthodontic space closure in
      the maxilla after traumatic loss of frontal teeth or aplasia of a lateral
      incisor. Comparison covers findings obtained from casts and cephalograms in 24
      patients with or without compensatory extraction. The findings indicate that
      acceptable results regarding axial tooth positioning and profile can be obtained
      without compensatory extraction. Prerequisites are distal occlusion of the first
      molars by one premolar width and continuous monitoring for regular overbite and
      uncrowded lower incisors. If orthodontic space closure can be achieved only by
      compensatory extraction, the indication for this space closure procedure calls
      for even more critical judgement.

PMID- 8986052
TI  - Need and desire for orthodontic (re-)treatment in 35-year-old Norwegians.
AB  - Long-term outcome of orthodontic care systems may be studied by examining
      malocclusion and treatment need in groups of treated and untreated adults. The
      objective of the present work was to investigate the professionally defined need
      as well as the need perceived by the individuals in an attempt to study the
      outcome of orthodontic services. The material comprised data from 111 individuals
      collected from a random sample of 35-year-olds from Oslo, Norway. From a clinical
      examination and measurements on dental study casts, the subjects were classified
      into either of 4 levels of need according to the Need for Orthodontic Treatment
      Index (NOTI) used by the Norwegian Health Insurance System. Perceived need for
      treatment was analyzed from responses to questions about satisfaction with dental
      appearance and desire for orthodontic treatment presented in a questionnaire.
      Satisfaction with dental appearance was recorded in 85% and 92% of untreated and
      previously treated, respectively. Desire for treatment was expressed by 19% of
      the untreated and 3% of the treated individuals. Occlusal anomalies were present
      among both the treated and untreated subjects, and the clinical significance of
      the malocclusion traits observed is discussed.

PMID- 8986053
TI  - Modification of the agar overlay assay: assessment of the influence of acrylics
      used in orthodontics on proliferation and differentiation of primary and
      transformed fibroblasts.
AB  - In orthodontics, removable acrylic appliances are preferably produced from
      methylmetacrylates. However, in the adjacent oral mucosal tissue, cell damage may
      be caused by the evaporation of residual monomer. The aim of this study was to
      modify the classic agar overlay assay in order to apply histochemical methods by
      comparing conventionally used transformed mouse fibroblasts (L-929) with primary
      human gingival fibroblasts to further elucidate the term toxicity. While
      proliferation was assessed via the incorporation of the base analogon
      bromdesoxyuridine, differentiation was investigated by detection of the
      fibroblast-specific intermediate filament vimentin. After the monomers had taken
      effect, reduced proliferation extending over the inhibition area was observed by
      indirect immunofluorescence, independent of cell type. In contrast to this
      observation, a few cells within the inhibition area which could not be clearly
      detected by neutral red staining still exhibited mitotic activity. Detection of
      the differentiation-specific intermediate filament vimentin was comparable with
      the degree of neutral red fading visible in the classic agar overlay assay. The
      study showed that the inhibition areas with primary gingival fibroblasts were
      smaller (approximately 1/3) after monomer action compared with conventionally
      applied transformed fibroblasts. The results indicate that the modified assay is
      comparable with the classic method. Evaluation of neutral red staining with
      respect to toxic material influence can moreover be supplemented by histochemical
      studies of typical cell properties.

PMID- 8986054
TI  - The influence of extraction versus non-extraction orthodontic treatment on the
      soft tissue profile.
AB  - The aim of the present study was to study profile changes following orthodontic
      harmonization of enlarged overjet and to attempt to trace predictive aspects
      regarding prognosis of the soft tissue changes. Lateral cephalograms and study
      models of 40 female patients, at least 12 years old at the start of treatment,
      with an overjet of > or = 6 mm were analyzed before (T1) and after treatment
      (T2). Twenty patients were treated without extractions, while in the remaining 20
      patients extractions of premolars were carried out bilaterally in both jaws. The
      2 groups were found to be highly homogeneous as regards overjet, cephalometric
      characteristics, space condition in the upper arch at T1 and both at T1 and T2 as
      regards age. The most striking aspect of the findings was the considerable amount
      of variability of the soft tissue changes. These changes were found to be rather
      unpredictable for the individual patient, since the regression models employed
      could give only a very wide individual prediction range. The relatively small
      changes registered, using superimposition methods, in both groups as regards the
      sagittal position of the lips in comparison to the very strong changes observed
      in relation to the esthetic line shows that the influence of the growth of the
      chin and/or the nose on the facial profile might be more important than the
      influence of the orthodontic treatment. The interpretation of the findings in the
      present study suggests that, apart from marked cases of skeletal convexity or
      concavity, the extraction versus non-extraction decision should be based
      primarily upon current knowledge of long-term stability of orthodontic treatment
      results.

PMID- 8986055
TI  - New clinical applications for the Jasper Jumper.
AB  - This article describes the use of the Jasper Jumper in the treatment of class III
      anomalies, both theoretically and with a case report. Contrary to its use in
      class II anomalies, the Jasper Jumper is fixed to the 6-year-molars in the lower
      jaw and in the canine area in the upper jaw. This results in a continuously
      working mechanism--independent of co-operation on the part of the patient.

PMID- 8986056
TI  - Improving dentofacial esthetics while paying attention to the anterior facial
      height index.
AB  - Prior to the pubertal growth spurt, a 12-year-old boy with a long face pattern,
      upper prognathia and class II,2 relationship was treated with a combination of
      edgewise appliance, statically determined intrusion base arch and Jasper Jumper.
      The clinical results show that, with the mechanotherapy presented here, good
      smile esthetics and normal class I occlusion were achieved. Furthermore, the
      cephalometric results reveal that, by using an appliance which leaves the
      extrusive effect on the molars small, the anterior facial height index can be
      kept constant even during the patient's growth phase, although contrary treatment
      goals such as incisor intrusion and occlusal correction must be met.
      Simultaneously, it could be demonstrated that Jasper Jumper treatment may not
      automatically lead to incisor flaring by individualizing the point of force
      application. In addition, reducing the deep overbite may prevent its destructive
      tendency, and the patient's growth pattern can be directed in a more horizontal
      direction.

PMID- 8986057
TI  - [ECG-gated dual-isotope myocardial SPECT with 201Tl and 99mTc-tetrofosmin:
      simultaneous assessment of stress/rest myocardial perfusion and left ventricular
      function].
AB  - ECG-gated dual-isotope acquisition protocol involving rest imaging with 201Tl and
      stress 99mTc-tetrofosmin (TF) SPECT was designed for the simultaneous assessment
      of rest/stress myocardial perfusion and rest ventricular systolic function. This
      study assessed the feasibility and diagnostic accuracy of this protocol. Forty
      five patients underwent the dual-isotope SPECT protocol. Twenty minutes after
      resting injection of 111 MBq of 201Tl, 370 MBq of 99mTc-TF was administered at a
      peak exercise. The dual-isotope gated SPECT acquisition was performed 1 hour
      later. Then, the regional count increase rate (%WT) of 99mTc-TF from end-diastole
      end-systole was calculated using an automated method which was developed for
      quantification of regional wall thickening based on circumferential profile
      analysis in our laboratory. Myocardial perfusion and contractility analysis was
      carried out using 8 segments of left ventricle with comparison of coronary
      angiographical findings. The sensitivity and specificity for the detection of
      diseased coronary vessels (> = or 75% stenosis) were 76% and 94%, respectively.
      Infarcted regions showing reversible defect had significantly greater %WT as
      compared with those with fixed defects (63 seg; 12.7 +/- 6.1% vs. 36 seg; 8.9 +/-
      7.2%, p < 0.01). In conclusion, this dual-isotope protocol has some advantages;
      i.e., shortening an examination time, having the exact registration of
      stress/rest perfusion, and simultaneous evaluation of resting regional wall
      thickening.

PMID- 8986058
TI  - [Regional cerebral blood flow measurements using 99mTc-ECD SPECT in patients with
      Alzheimer's disease (ad) in the early stage].
AB  - Regional cerebral blood flow (rCBF) measurements using a Patlak plot method and
      SPECT with 99mTc-ECD were performed in 10 patients with possible Alzheimer's
      disease (AD), 14 patients with probable AD, and 11 age-matched normal control
      subjects. The whole brain CBF for the probable group showed significant reduction
      to 37.2 ml/100 g/min as compared with the normal value of 42.1 ml/100 g/min,
      whereas the possible group did not show significant reduction of the whole brain
      CBF. In the possible and probable groups, rCBF values in the bilateral
      hippocampi, supramarginal gyri, angular gyri were lower than normal values.
      Moreover, in the probable group, rCBF values showed significant decrease in the
      superior, middle and inferior temporal gyri. The whole brain CBF and rCBF,
      especially in the bilateral hippocampal regions, showed significant positive
      correlation with the scale of MMSE and HDS-R. These results suggest that
      noninvasive rCBF measurements using 99mTc-ECD are quite useful for the early
      diagnosis of AD.

PMID- 8986059
TI  - [Imaging of strontium-89 uptake with bremsstrahlung using NaI scintillation
      camera].
AB  - Strontium-89 chloride is widely available in the U.S. and Europe for patients
      afflicted by bone metastasis associated with pain. 89Sr is a pure beta-emitter
      and it is thought to be difficult to estimate its distribution externally. We
      tried to image the distribution of 89Sr uptake with bremsstrahlung from beta
      minus decay of 89Sr by using Nal scintillation camera. Pronounced 89Sr
      depositions in the bone metastatic sites were imaged in the energy windows from
      50 keV to 150 keV bremsstrahlung. The distribution of these depositions
      corresponded to 99mTc-HMDP image may be suspected to the effectiveness of this
      therapy. The identification of 89Sr distribution might be useful in evaluating
      the bone marrow radiation dose too.

PMID- 8986060
TI  - [Noninvasive quantitative measurements of regional cerebral blood flow using
      technetium-99m-L, L-ECD SPECT activated with acetazolamide].
AB  - To evaluate noninvasive regional cerebral blood flow (CBF) measurements using
      technetium-99m-L, L-ethyl cysteinate dimer (99mTc-ECD), radionuclide angiography,
      resting- and acetazolamide-activating-SPECT studies were performed during about
      one hour. Forty-four cases with diagnosis of cerebral ischemic disorders were
      studied. For 36 cases (Group "Acz"), radionuclide angiography was performed
      immediately after intravenous bolus injection of 300 MBq of 99mTc-ECD, followed
      by the consecutive SPECT studies. In the midst of the first SPECT study,
      acetazolamide was administered. Just after the completion of the first SPECT
      study, another 300 MBq of 99mTc-ECD was added and the second SPECT study was
      started. For the remaining 8 cases (Group "Placebo"), physiological saline was
      administered instead of acetazolamide. Quantitative flow-mapping image was
      calculated from the qualitative SPECT image by the application of Patlak plot
      graphical analysis and Lassen's correction. Group "Placebo" showed no increase of
      mean CBF (mCBF) between the resting- and the placebo-challenged-SPECT image (2nd
      mCBF/1st mCBF; 98 +/- 5%). Group "Acz" showed 124 +/- 15% increase of mCBF under
      acetazolamide activation. By use of these quantitative flow-mapping images,
      acetazolamide-activated CBF increase was recognized clearly and easily. This
      noninvasive method is easy to perform and may be helpful to measure cerebral
      perfusion changes in the acetazolamide test.

PMID- 8986061
TI  - [Analysis of contributing factors with high renal uptake of 99mTc-MDP after anti
      cancer chemotherapy including cisplatin].
AB  - We studied the effect of anti-cancer chemotherapy including cis-platin (CDDP) on
      renal high uptake of 99mTc-MDP using renal accumulation index (RAI) which was
      defined as a ratio of the densities between kidneys and lumbar bodies. We
      analyzed 21 cases who received bone scintigraphy within 30 days after
      chemotherapy. High RAIs were observed in 15 cases (71.4%). We compared the
      relationship between the RAI and time interval of CDDP administration and bone
      scintigraphy, total dose of CDDP, BUN and age. High RAIs were inversely related
      to the time interval and no patient showed high RAI when bone scintigraphy were
      studied later than 17 days after chemotherapy. BUN level were related to RAI.
      But, dose of CDDP and ages were unlikely responsible for the RAI values in this
      study. We summarized that high renal uptake of 99mTc-MDP was likely to be due to
      short time interval after chemotherapy.

PMID- 8986062
TI  - [Evaluation of renal allograft dysfunction employing dynamic SPECT with 99mTc
      MAG3 and graph plot analysis].
AB  - To estimate renal blood flow and tubular function in transplanted kidneys, we
      applied the 4 compartments model and the graphic analysis method to 99mTc-MAG3
      dynamic SPECT and calculated some parameters, i.e. K1 (renal influx rate
      constant), K3 (tubular transporting rate constant), Vd12 (intrarenal distribution
      volume), and others. Twenty-three renal transplant recipients were examined and
      divided into following 3 groups according to their serum creatinine levels (SCr);
      Group I: less than 1.3 mg/dl (1.1 +/- 0.3, n = 7), Group II: 1.4-2.5 mg/dl (1.8
      +/- 0.3, n = 11), and Group III more than 2.6 mg/dl (3.9 +/- 0.9, n = 5). The K3
      value became lower in the order of Group I > II > III, and well correlated with
      blood urea nitrogen (BUN, r = -0.95, p < 0.001) and creatinine clearance (Ccr, r
      = 0.78, p < 0.001). The K1 value reduced markedly in Group III despite of no
      difference between Group I and II. Although the K1 value also correlated with
      SCr, BUN and Ccr, correlation coefficients were smaller than those with the K3.
      Effective renal plasma flow derived from K1 and K3 showed a good correlation with
      the tubular extraction rate by Bubeck's method. From these results and clinical
      conditions including histopathological findings it is suggested that K1, K3 and
      Vd12 are useful parameters of renal central arterial blood flow, renal peripheral
      arteriolar blood flow and renal 99mTc-MAG3 uptake function, respectively.

PMID- 8986063
TI  - [Comparison of cerebral blood flow in primary visual cortex by administration of
      99mTc-ECD while having eyes open or closed].
AB  - Four healthy volunteers were administered 99mTc-ECD while having their eyes open
      or closed (by an eye mask) on different days and the accumulation of the tracer
      in their primary visual cortex was compared. The accumulation in the cerebellum
      and the primary visual cortex was about the same when the volunteers were
      administered the tracer while having their eyes closed. On the other hand, the
      accumulation was higher in the primary visual cortex than the cerebellum when the
      volunteers were administered the tracer while having their eyes open. In the
      primary visual cortex, the accumulation of the tracer was 15% higher on the
      average when the tracer was administered while having their eyes open than the
      value obtained while having their eyes closed. It was assumed that 99mTc-ECD
      depicted the increase of the regional cerebral blood flow at natural state of
      opened eyes without active stimuli such as photic stimulation.

PMID- 8986065
TI  - [Mechanism and results of bacterial adhesion in urinary tract infections].

PMID- 8986064
TI  - [89Sr Therapy for pain relief in patients with bone metastases].
AB  - Radioactive strontium chloride (89Sr) was administered for pain relief in 6
      patients with bone metastases (4 prostate cancer and 2 breast cancer patients).
      Out of 6 patients, 2 showed apparent relief of bone pain and improvement of QOL,
      and 3 showed slight relief of the pain with or without improvement of QOL; that
      is, 83% was effective. Side effects were seen in 2 patients; transient
      deterioration of bone pain in one patient and bone marrow suppression in the
      other patient. The patient who showed bone marrow suppression had rather more
      lesions of bone metastasis (diffuse metastasis) and least urinary excretion of
      the radioactivity. Urinary excretion for 2 days varied 5 to 40% of the
      administered dose and was less in the patients with more metastatic lesions.

PMID- 8986066
TI  - [Destructive respiratory infection].

PMID- 8986067
TI  - [The effect of recombinant human colony stimulating factor (G-CSF) on the
      function of human blood and urinary leukocytes].
AB  - To study the function of leukocyte in urinary tract infection (UTI), the effect
      of granulocyte colony-stimulating factor (G-CSF) and various osmolarities on the
      function were studied. The superoxide production of blood leukocytes increased by
      treatment of G-CSF with its dose dependency. This effect was not observed in
      urinary leukocytes. This increased function was well preserved even in higher
      osmotic atmosphere when previously treated by the G-CSF. Therefore, urinary
      leukocyte activated by G-CSF and migrating from the blood through the tissue may
      still have its function and work in the patients with UTI.

PMID- 8986068
TI  - [The taxonomic distribution, characteristic and susceptibility against
      antimicrobial agents of methicillin-resistant staphylococci isolated from blood].
AB  - The species, mecA gene, beta-lactamase activity, the ability of slime formation
      and drug susceptibilities of 386 strains of staphylococci which were isolated
      from blood in our laboratory were studied. The coagulase typing of each strains
      identified as S. aureus was also determined. These 386 strains consisted of
      various species, e.g., S. aureus, S. epidermidis, S. capitis, S. caprae, S.
      hominis, S. simulans, S. haemolyticus, and S. lugdunensis. mecA (methicillin
      resistant gene) was detected in 84 (67.7%) of 124 S. aureus and 195 (75.3%) of
      259 CNS, but there was no statistical difference. However mecA positive rate was
      higher in S. epidermidis and S. caprae, lower in S. hominis compared with S.
      aureus, S. lugdunensis having mecA has not been reported, but one of two our S.
      lugdunensis strains had mecA. The positive rate (77.4%: 65/84) of beta-lactamase
      of methicillin-resistant Staphylococcus aureus (MRSA) was lower than that (95.5%:
      187/195) of methicillin-resistant coagulase-negative staphylococci (MRCNS).
      Concerning the ability of slime formation, CNS had higher positive rate,
      especially in case of MRCNS (46.2%: 84/182) than S. aureus. On the other hand,
      MRCNS showed a tendency to be less resistant to some antimicrobials than MRSA.
      Especially against cephalothin (CET), the resistant rate of MRSA and MRCNS were
      86.9% and 5.6%, respectively. Among the main species of MRCNS, S. capitis and S.
      caprae were more resistant than S. epidermidis and S. simulans to cefaclor (CCL),
      cefmetazole (CMZ), flomoxef (FMOX) and fosfomycin (FOM). Hereafter, one should be
      careful about infectious disease caused by CNS especially in immuno-compromised
      host, because many species of CNS have higher positive rate of beta-lactamase and
      slime formation than S. aureus beside mecA.

PMID- 8986069
TI  - [Characteristics of Salmonella strains isolated from sporadic diarrheal cases
      during 1992-1994 in the Philippines].
AB  - A total of 263 Salmonella strains isolated in Metro Manila, the Philippines from
      1992 to 1994, were examined for their serovar-distribution and drug-resistance.
      Salmonella serovar Typhi (S. Typhi) and S. Enteritidis phage type was also
      tested. The serological typing results showed that the strains were classified
      into 10 O-groups and 32 serovars. S. Weltevreden, S. Enteritidis, S. Typhi, S.
      Typhimurium, and S. Derby were predominant in the serovars identified. The drug
      resistance test using nine drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM, and NFLX)
      showed that 95 strains (36.1%) were resistant to any of the seven drugs except
      FOM and NFLX. The serovars of a high resistant rate were S. Ruiru (100%), S.
      Typhimurium (87.0%), S. Senftenberg (80.0%), S. Derby (66.7%), and S. Agona
      (50.0%). Drug-resistance patterns of the resistant strains varied to 21 types,
      and 80 of them were multidrug-resistant. Phage types of 37 S. Typhi strains were
      B1 (27 strains), E2 (6 strains), and others (4 strains). Phage types of 38 S.
      Enteritidis strains were 4 (32 strains), 7 (3 strains), and others (3 strains).

PMID- 8986070
TI  - [Laboratory virological diagnosis of imported dengue cases].
AB  - Suspected dengue cases in Japan during the period of 1985-1995, 173 cases with
      unknown febrile illness entering or returning from mostly southeast Asia, were
      tested by serology and RT-PCR gene amplification. Seventy seven cases were
      confirmed by a significant rise of dengue 2 (Den 2) HI antibody in paired sera or
      by detection of HI antibody titer higher than 1:320 in single serum. The other 3
      cases with antibody levels not higher than 1:80 in paired sera and 12 cases with
      an antibody 1:160 in single sera were positively suspected of dengue infection
      but were not confirmed. Countries of origin of confirmed cases were Thailand (39
      cases), Philippinse (15), India (13), and Indonesia (9). Sera of dengue cases
      showed high degrees of cross reactivity of Japanese encephalitis virus (JEV) in
      HI test but not in IgM capture ELISA. Sera of confirmed JEV-infected cases,
      however, showed practically no cross reactivity to Den 1 4 in HI test, suggesting
      unilateral cross reactivity of HI antibody. RT-PCR detected the Den 1 genome in
      sera of 3 cases obtained within 3 days after onset and the Den 2 genome in serum
      of case 4 days after onset. Although the number is limited, 92 (53%) out of 173
      cases of febrile illness of unknown etiology entering Japan from tropical
      countries were either confirmed or positively suspected to be dengue fever.
      Considering possibilities of under reporting, importations of tropical viral
      infections should be bigger in number and will necessitate our intensified
      alertness.

PMID- 8986071
TI  - [Clinical study of 18 patients whom MRSA was detected from stool--especially
      about comparison enterocolitis with colonization].
AB  - We studied the clinical aspects of 18 patients from whom MRSA was detected from
      the stool and compared with 9 enterocolitis cases (7 male, 2 female, median age
      72.4 y.o.) with 9 colonization cases (5 male, 4 female, median age 70.2 y.o.)
      from 1991 June to 1995 May. Cases of postoperative, use of anti-peptic ulcer
      drugs and administration of antibiotics for enterocolitis were more than that of
      colonization. On the other hand, eatable patients in the colonization group who
      could take food orally were more in number. Many patients of both enterocolitis
      and colonization were colonized in the respiratory tract. Drug sensitivity of
      MRSA in both cases were almost the same and the coagulase type were all that of
      II. Three courses on how MRSA enterocolitis occurs is considered. At first,
      colonization in the respiratory tract, second, proliferation of MRSA in the
      higher pH gastric juices as a result of gastrectomy or use of anti-peptic ulcer
      drugs, and third, selection of MRSA after administration of antibiotics.

PMID- 8986072
TI  - [Double infection of Chlamydia pneumoniae and Mycoplasma pneumoniae in children].
AB  - There have been fewer reports on Chlamydia pneumoniae infection during childhood
      than those in adults, although many of the C. pneumoniae infections occurred
      during childhood based on prevalence of the antibody. And there have been no
      reports concerning the double infection of C. pneumoniae and M. pneumoniae. We
      reported three cases of children with the double infection. We diagnosed this
      from significant alteration of these antibodies from the acute to convalescent
      phases. We omitted the cases without significant alteration of the antibodies,
      even diagnosed from isolation or detection of the antigens in the samples by
      direct fluorescent antibody. Case 1 was an 8-year-old-boy who was admitted to our
      hospital because of fever, cough with vomiting and erythema multiforme. The
      symptoms did not subside after administration of clindamycin but subsided after
      minocycline. Case 2 was an 1-year-old-boy who was admitted because of fever,
      cough, rhinorrhea and vomiting. C. pneumoniae organisms were isolated from the
      pharyngeal swab specimen, the symptoms subsided after administration of
      clindamycin. Case 3 was a 9-year-old boy who was admitted because of fever and a
      cough followed by erythema multiforme. The symptoms did not decrease after
      administration of clindamycin but after minocycline. The characteristic of these
      cases are a strong cough with vomiting, weak response of acute reactants on the
      laboratory data, and skin eruption similar with that due to M. mycoplasmae in two
      of the three cases. We suspect that these double infections may induce the
      eruption, about which there have been no previous reports.

PMID- 8986074
TI  - [A case of fluminant septic shock due to Streptococcus agalactiae in a patient
      with MPO-ANCA related glomerulonephritis].
AB  - Recently group A Streptococcus toxic shock like syndrome (TSLS) has been
      reported, but as for group B streptococcus (S. agalactiae) infection, there have
      been little documentation in the literature. We report a case of fluminant septic
      shock due to Streptococcus agalactiae (S. agalactiae). A 72-year-old male was
      admitted to our hospital because of general fatigue and azotemia. He was
      diagnosed as having MPO-ANCA related glomerulonephritis and treated with steroid
      therapy. Gradually he was doing well. On the 228th hospital day, he suddenly had
      tachypnea, transient conscious disturbance, and profound hypotension. About 16
      hours later, he died despite intensive treatment. S. agalactiae was isolated from
      the blood. Autopsy revealed bilateral bronchopneumonia and shock liver. To our
      knowledge, this is the first report of septic shock caused by S. agalactiae.

PMID- 8986073
TI  - [Invasive pulmonary aspergillosis caused by aspiration of polluted water after
      nearly drowning].
AB  - A 21-year-old male nearly drowned in a reservoir by a traffic accident and he
      aspirated a large mount of polluted water containing Aspergillus fumigatus. On
      admission to our hospital, he was alert but cyanotic. Chest rentogenograms showed
      scatter infiltrative shadows in bilateral lung fields. We administered
      methylpredonizolon and antimicrobial agents immediately because of respiratory
      failure which was rapidly progressing. During the following six days,
      infiltrative shadows diminished but multiple nodular shadows in both lung fields
      appeared. The diagnosis of pulmonary aspergillosis was confirmed by serological
      and microbiological studies. Intravenous amphotericin B and oral itraconazol were
      administrated, and clinical improvement was observed.

PMID- 8986075
TI  - [Effects of tea catechin and specific antibody of influenza viruses].

PMID- 8986076
TI  - [The prevalence of Helicobacter pylori positive serology in asymptomatic Japanese
      children].

PMID- 8986077
TI  - [An investigation of the factors influencing serum pepsinogen levels--sex, age,
      smoking, drinking].
AB  - BACKGROUND: Until now, the influence of sex, age, smoking, drinking on serum
      pepsinogen levels has been assessed by single regression analysis. However, the
      influence of those factors on pepsinogen levels should be assessed exactly by
      multiple regression analyses. SUBJECTS AND METHODS: 891 subjects were collected
      from by questionnaire and serum tests. Analyses were done with serum pepsinogen I
      (PG I), pepsinogen II (PG II) and pepsinogen I/II ratio (PG I/II) as a criterion
      variable and as categorized explanatory variables, sex, age, current or past
      smoking habit, and current drinking habit. And analyses are done by Mann-Whitney
      U test, correlation coefficient, single regression method, multiple regression
      method. RESULTS: PG I level is significantly higher in men than in women by Mann
      Whitney U test. But the effect of sex factor is not remarkable by multiple
      regression analyses. PG II level increased and PG I/II level decreased with
      progression of age by all analyses methods. Current or past smoking elevates PG I
      level by Mann-Whitney U test, but current smoking dose and past smoking amount
      showed no dose-dependent associations with PG I level. Current drinking elevates
      PG I level by Mann-Whitney U test, but current drinking dose showed no dose
      dependent associations with PG I. However, the effects of current smoking and
      current drinking to serum PG levels is not so large by multiple regression
      analyses. CONCLUSION: The effects of sex, current smoking and current drinking to
      serum PG levels are not remarkable by multiple regression analyses.
      Significantly, PG II level increased and PG I/II level decreased with progression
      of age. Therefore it may not be necessary to consider the effects of sex, smoking
      habit and drinking habit when serum pepsinogen levels are used as markers for
      gastric cancer.

PMID- 8986078
TI  - [Pancreas like acinar glands in the esophagogastric junctional mucosa].
AB  - Esophagogastric material resected for malignancy, obtained from 52 adult
      patients, was examined histologically. In a longitudinal examination of 32 total
      gastrectomies, intramucosally located pancreatic acinar cell-like cells (PALC)
      were observed frequently (10 of 12 patients, p < 0.05) only in the uppermost one
      sixth part, especially in a 10 mm-long zone around the squamocolumnar junction
      (SCJ). Entire sampling of the junctional mucosa revealed no significant
      difference in frequency of occurrence of PALC between esophageal and gastric
      cancer groups (13 of 20 patients, 20 of 31 patients, respectively). In 59
      sections examined precisely, 43 sections showed zonal atrophy of the gastric
      glands. More than half of these zones (25 of 44 zones) did not overlap with 4 mm
      long SCJ zones. In the latter zones, stratified columnar epithelia, epithelial
      islands, and PALC were observed more frequently, although intestinal metaplasia
      was not. These data suggested that the occurrence of PALC is correlated with the
      anatomical site, i.e. SCJ, but not with such ill conditions, i.e. atrophic
      gastritis or gastric cancer. PALC in the SCJ may be orthotopic.

PMID- 8986079
TI  - [Validation of the hospital anxiety and depression scale in a gastro-intestinal
      clinic].
AB  - This study examined the validity of the Japanese version of the hospital anxiety
      and depression scale (HAD) in a gastro-intestinal outpatient clinic. One hundred
      and twenty-three men and 142 women consulting a gastro-intestinal outpatient
      clinic at a primary care hospital in Kyoto during 1995 were surveyed. Item
      remainder correlation and internal consistency were examined for reliability.
      Concurrent validities were examined using the stait-trait anxiety inventory
      (STAI) and Zung's self-rating depression scale (SDS). The prevalence of
      psychiatric disorder in this population ranged from 27% to 39%. Cronbach's
      coefficients were greater than 0.8 for the anxiety subscale and more than 0.7 for
      the depression subscale. Spearman's correlation of the anxiety subscale scores
      and the STAI were r = 0.678 for men, and r = 0.717 for women. The correlation of
      depression subscale scores and SDS were r = 0.457 for men, and r = 0.565 for
      women. It is suggested that the use of the HAD to general hospital outpatients
      clinic would facilitate detecting emotional disorders in outpatients.

PMID- 8986080
TI  - [The course of gastric type epithelium in duodenal ulcer and duodenitis; role on
      the eradication of Helicobacter pylori].
AB  - The course of gastric type epithelium during the healing process and beyond the
      scarring stage of duodenal ulcer was studied in patients with and without
      Helicobacter pylori (H. pylori) eradication. Materials were consist of 110
      patients with active H. pylori ulcers, 27 patients with H. pylori positive ulcer
      scars and 6 patients with active H. pylori positive duodenitis. The results
      obtained were as follows. 1) In the non-eradication group, the degree of gastric
      type epithelium increased as the ulcers healed, but gastric type epithelium
      remained immature compared with the eradication group. 2) In the non-eradication
      group, the degree of gastric type epithelium decreased subsequently with or
      without recurrence of the duodenal ulcer. Under H. pylori positive condition, the
      degree of gastric type epithelium appeared to be reduced because of invasion by
      H. pylori. When this condition continued, ulcers probably recurred because of
      diminished defences against acid in damaged areas of gastric type epithelium. 3)
      In the successful eradication group, gastric type epithelium became well
      developed and mature state (grade 4), and remained in this condition for long
      period because it was not invaded by H. pylori. The appearance of mature state of
      gastric type epithelium appears to play a role in the prevention of ulcer
      recurrences by maintaining an adequate defence mechanisms against acid. 4) In the
      unsuccessful eradication group, the degree of gastric type epithelium remained
      lower mature state than that of successful eradication group. 5) In cases of H.
      pylori positive ulcer scar, the degree of gastric type epithelium reached also
      well developed and mature state when H. pylori was successfully eradicated, and
      maintained in this condition for a prolonged period. Ulcer recurrence was not
      observed. 6) In case of H. pylori positive duodenitis, the degree of gastric type
      epithelium reached mature state after successful eradication, and endoscopic
      findings of inflammation was improved.

PMID- 8986081
TI  - [Effect of high dose interferon alpha-2b therapy for chronic hepatitis C].
AB  - We evaluated the efficacy of high dose interferon therapy in 122 patients with
      chronic hepatitis C between 1992 and 1995. They received 612 to 836 mega-units
      (MU) of recombinant interferon alpha-2b as a total dose during a 6-month
      treatment in our hospital. Fifty one patients (41.8%) achieved complete response
      (CR) which was defined as persistent normalization of serum aminotransferase
      levels and disappearance of serum HCV-RNA for more than 6 months after the end of
      interferon administration. However, there were no CR in patients with genotype II
      and in those with serum HCV-RNA levels above 1.5 Meq/ml, quantified by branched
      DNA probe assay. The rate of CR was not increased even if a total dose of IFN
      administration was increased from 612 MU to 836 MU. These results indicate that
      some new regimen of interferon therapy is necessary for these cases with high
      titer of serum HCV-RNA and genotype II to increase the rate of CR.

PMID- 8986082
TI  - [A case of clonic cancer with Leser-Trelat sign].

PMID- 8986083
TI  - [A case of double cancer, cholangiocellular and hepatocellular carcinoma
      associated with autoimmune hepatitis].

PMID- 8986084
TI  - [A case of alpha-fetoprotein-producing pancreatic carcinoma--review of 41 cases
      reported in Japan].

PMID- 8986085
TI  - [A long surviving case of carcinoma of the common hepatic duct treated by
      chemotherapy with CDDP in the percutaneous external biliary tube and
      endoprosthesis].

PMID- 8986086
TI  - [A case of encapsulating peritonitis associated with pancreatic ascites induced
      by carcinoma of the pancreas].

PMID- 8986087
TI  - [A case of pancreatic pleural effusion and ascites treated successfully with
      conservative measures including octreotide and nafamostat mesilate].

PMID- 8986088
TI  - [Successful treatment of a large pancreatic pseudocyst with a percutaneous
      catheter drainage and a somatostatin analogue--report of a case].

PMID- 8986089
TI  - [Four cases of retroperitoneal schwannomas].

PMID- 8986090
TI  - [Child neurology: what should it be?].

PMID- 8986091
TI  - [Abnormal metabolism of fatty acids and ketone bodies in Duchenne muscular
      dystrophy, and the effect of biotin on these abnormalities].
AB  - It has been reported that serum levels of ketone bodies often elevate in patients
      with Duchenne muscular dystrophy (DMD). The cause of this abnormal metabolism,
      however, has not been elucidated. In this study, serum levels of ketone bodies
      were measured in the early morning in patients with DMD, congenital muscular
      dystrophy and cerebral palsy. Serum free fatty acids (FFA), glucose, and
      thickness of subcutaneous fat were also measured. Ketone bodies elevated in most
      DMD patients, but not elevated in patients with the other disorders.
      Hyperketonemia in the DMD patients was accompanied by elevation of the FFA level,
      but no correlation was seen between hyperketonemia and the creatine kinase level
      or the severity of muscle involvement. No differences were found between DMD
      patients and others in the levels of FFA, glucose and thickness of subcutaneous
      fat. These results indicate that DMD patients are more prone to ketosis than the
      others. The effect of biotin administration (2 mg/day) on hyperketonemia also was
      investigated in 11 patients with DMD. The levels of total ketone bodies decreased
      by biotin administration for 2 weeks. These data suggest that the utilization of
      FFA and ketone bodies may be impaired in DMD patients. Biotin treatment will be
      useful for improving the abnormal metabolism of ketone bodies in DMD patients.

PMID- 8986093
TI  - [Gestational age, birth weight, degree of motor impairment, and causes of brain
      damage in sixty-eight patients with cerebral palsy identified in a community
      (birth year 1985-1991)].
AB  - Gestational age, birth weight, degree of motor impairment, and causes of brain
      damage were analyzed in 68 patients with cerebral palsy born and identified in a
      community. This community is located in the suburban Tokyo with about 480,000
      inhabitants. In the period of 1985-1991, it had 34,289 live births (annual birth
      rate 1.0%) and all the births were recorded at public health centers. Sixty-eight
      patients with cerebral palsy were identified with the incidence rate of 2.0/1,000
      birth. Twenty out of 68 cases (29%) were born before 37 weeks of pregnancy and 27
      out of 68 cases (40%) were born with birth weight less than 2,500 gm. Patients
      with full term gestational weeks had severe motor impairment compared to preterm
      cases. Brain damages occurring in the prenatal period played a major role as the
      cause of cerebral palsy in the full-term-born group, and brain damage occurring
      in perinatal period played a major role in the preterm-born group. We conclude
      that to lessen new cases of cerebral palsy, we need two strategies; prevention of
      brain damages in the prenatal period, and prevention of preterm births.

PMID- 8986092
TI  - [Causative factors resulting in intractability of congenital hydrocephalus-
      analysis of psychomotor development and MRI findings of the brain in sixteen
      congenitally hydrocephalic patients].
AB  - Sixteen patients out of 58 children with congenital hydrocephalus were
      retrospectively investigated in terms of their psychomotor development and
      morphological findings of the brain by magnetic resonance imaging (MRI), and
      morphological backgrounds of the brain in patients affected by "intractable
      hydrocephalus" were intended to be clarified. The 16 patients were primarily
      diagnosed as having aqueductal stenosis or communicating hydrocephalus during the
      era before introduction of MRI. On the basis of the rate of head growth, sixteen
      patients were divided into three groups; group-1: overt neonatal hydrocephalus (5
      cases) ; group-2: rapidly progressive hydrocephalus with normal head
      circumference at birth (5 cases); and group-3: slowly progressive hydrocephalus
      with its onset after the neonatal period (6 cases). Psychomotor development of
      the 16 cases was analyzed by using various methods including the Tanaka-Binet
      intelligence test and WISC-R. Four cases in group-1 and all cases in group-2 were
      found to have IQ or DQ below 50, while the other remaining cases were found to
      have IQ of 82 in group-1 (one case) and IQ ranging from 67 to 113 in group-3. MRI
      performed in those 9 cases with IQ below 50 revealed various morphological
      abnormalities of the brain. Those abnormalities were characterized by disturbance
      of organogenesis and/or histogenesis of the brain dating from the first 20 weeks
      of fetal life. It is strongly suggested that in the pathogenesis of intractable
      hydrocephalus developmental malformation of the brain occurring during the first
      20 weeks of gestation are involved. Functional and morphological impairments of
      the brain possibly caused by progression of fetal hydrocephalus and delay of CSF
      diversion before and after birth seem important in the pathogenesis of
      intractable hydrocephalus.

PMID- 8986094
TI  - [The volume of white matter in cerebral palsy with MRI findings of
      periventricular leukomalacia].
AB  - The volume of the white matter in 5 cases of cerebral palsy (CP) of term delivery
      without hypoxic episodes with MRI findings of periventricular leukomalacia (PVL),
      was compared with that of 12 CP cases in preterm delivery manifesting typical MRI
      findings of PVL. It was significantly decreased in the latter. The volume for the
      full-term CP cases was the same as that for children born at term and developing
      normally. These findings suggest that the grade of perinatal brain damage is
      different between the full-term and pre-term CP cases, and that the intrauterine
      timing of fetal circulatory disturbance is different.

PMID- 8986095
TI  - [Efficacy and side effects of lidocaine by intravenous drip infusion in children
      with intractable seizures].
AB  - Intravenous drip infusions of lidocaine (IDIL; 1-5 mg/kg/h) were performed in ten
      patients with intractable seizures. The medication was very effective in five
      patients, whose seizures disappeared immediately after the treatment of IDIL. In
      four patients, the medication proved to be effective judging from decreased
      incidence of seizures. In one patient with intractable seizures, the therapy was
      not effective. In nine patients with the effective medication, five had
      generalized seizures and four had partial seizures. Side effects were observed in
      four patients. Two patients had muscle hypotonia, one had visual and auditory
      hallucination and another had bradycardia. These symptoms completely disappeared
      after the ceasing of IDIL. Serum concentrations of lidocaine at the appearance of
      the side effects ranged from 1.8 to 4.7 micrograms/ml, although the toxicity
      level is more than 5.0 micrograms/ml for arrhythmic adult patients. These
      findings suggest that the serum toxic level of lidocaine in children is different
      from that in adults, and that careful observation and appropriate management for
      the children with lidocaine therapy should be necessary, even though the serum
      level of lidocaine ranges within the therapeutic level.

PMID- 8986096
TI  - [Cerebral cortical dysplasia associated with epilepsy: MRI and clinical aspects].
AB  - Clinical and electroencephalographic (EEG) studies were performed in nine
      patients with cerebral cortical dysplasia (CD). Interictal single photon emission
      computed tomography (SPECT) using 99mTc-hexamethyl propylene amine oxime were
      studied in four patients. A patient with hemimegalencephaly and agyria had poor
      outcome in both developmental and epileptic aspects. The prognoses of clinical
      seizures were generally related to the severity, location and size of CD. The
      size of the lesion was not always correlated with the clinical seizure outcome.
      Four patients had focal pachygyria. Clinical pictures were diverse in these
      patients. One patient underwent callosotomy for the control of intractable
      seizures. The others had no clinical seizures despite of the appearance of
      paradoxical discharges in the area of pachygyria. The distribution of CD detected
      by MRI did not always correlate with that of paradoxical discharges in EEG and/or
      hypoperfusional areas seen in SPECT. These findings suggest that a detailed
      neuroimaging study is useful to elucidate the epileptogenesis in patients with
      CD, and that all the cortical abnormalities in patients with intractable epilepsy
      are not detected by MRI.

PMID- 8986097
TI  - [Chronic respiratory failure in a case with juvenile-onset acid alpha-glucosidase
      deficiency; successful therapy with nasal intermittent positive pressure
      ventilation (NIPPV)].
AB  - A 13-year-old boy with juvenile-onset acid alpha glucosidase deficiency was
      reported. Proximal muscle weakness including respiratory muscles and scoliosis
      progressed since nine year of age. He developed nocturnal dyspnea and daytime
      somnolence at age 13. His arterial blood gas analysis showed hypoxemia (PO2 54.1
      mmHg) and hypercapnia (PCO2 72.3 mmHg), and spirometry showed significantly
      decreased vital capacity (% VC 21%). He was treated with nocturnal NIPPV
      employing a device for delivering bilevel positive airway pressure (Bi-PAP).
      Nocturnal dyspnea and daytime somnolence rapidly disappeared with nocturnal
      ventilatory support. Daytime arterial PO2 and PCO2 improved after the therapy,
      namely 74.8 mmHg and 64.1 mmHg respectively. We conclude that NIPPV is a
      noninvasive and effective therapy for respiratory failure in patients with
      chronic progressive neuromuscular disorder including acid alpha glucosidase
      deficiency.

PMID- 8986098
TI  - [Reversible changes of cranial MRI in a girl with SLE].
AB  - The 11-year-old girl had hypertension and generalized tonic-clonic convulsions
      during the steroid pulse therapy. Her cranial T2-weighed MRI showed small areas
      of high signal intensity in the right occipital lobe. Her neurological findings
      were normal. After 2 months of steroid pulse therapy, multiple high signal
      intensities were demonstrated on T2-weighed MRI. After 5 months of the therapy,
      however, only a small T2-weighed MRI spot of high signal intensity in the white
      matter was observed, and the multiple lesions disappeared. On follow up, she did
      not show any neurological defects. It is postulated that not only steroid pulse
      therapy-induced hypertension but also SLE-induced angiopathy caused such flexible
      lesions. According to the literature, these lesions can be considered to be edema
      around small vessels. Such MRI findings have been reported in adult patients with
      SLE, but to our knowledge there have not been reports on children with SLE.

PMID- 8986099
TI  - [Identification of impaired cholesterol biosynthesis in a Japanese patient of
      Smith-Lemli-Opitz syndrome].
AB  - We reported the decreased level of cholesterol as well as the elevated levels of
      7- and 8-dehydrocholesterol in the serum and erythrocytes of a Japanese patient
      with Smith-Lemli-Opitz syndrome. These findings suggested that the detection of
      these precursors of cholesterol synthesis should become an important biochemical
      parameter for this syndrome in which clinical features are not always obvious.

PMID- 8986100
TI  - [A case of isolated ACTH deficiency with neuromuscular symptoms].
AB  - A female case of isolated ACTH deficiency associated with neuromuscular symptoms
      was reported. Although her initial development was delayed with perinatal
      troubles, developmental catch up was seen. The patient complained of general
      fatigue with weakness and poor school performance at the age of eleven. Muscle
      weakness predominant to the proximal portion and mental dullness were suspected
      from neurological examination. Her laboratory data were as follows; mild
      elevation of CK in serum, subclinical thyroidal dysfunction, abnormal
      electrocardiogram, slow wave activity on electroencephalogram, delayed nerve
      conduction velocity, and localized hypoperfusion of cerebral blood flow on single
      photon emission computed tomogram. Histological examination of muscle biopsy
      demonstrated only mild fiber size variation. During two years' follow-up, her
      intelligence quotient fell down, while muscle weakness did not progress
      significantly. At the age of fourteen, a low level of plasma ACTH was pointed out
      by chance and a definitive diagnosis was obtained by endocrinological
      examinations; no response of ACTH and cortisol on insulin stimulation, delayed
      response of cortisol on continuous ACTH stimulation, and no response of plasma
      ACTH on corticotropin releasing hormone stimulation. Other signs of
      adrenocortical insufficiency, such as hypoglycemia and abnormal serum
      electrolytes, were not observed during the clinical course. This case suggested
      that isolated ACTH deficiency should be considered for differential diagnosis of
      neuromuscular disorders.

PMID- 8986101
TI  - [Valproate-induced pancytopenia in a patient with infantile spasms].

PMID- 8986102
TI  - Gastropathy and NSAIDs: healing gastric and duodenal lesions and prophylaxis with
      PGs.

PMID- 8986103
TI  - Hepatitis C: ribavirin and/or interferon?

PMID- 8986104
TI  - Liver resection and liver transplantation in hepatocellular carcinoma.

PMID- 8986105
TI  - Detection of Chlamydia trachomatis by immunofluorescence, papanicolaou and
      immunoperoxidase in women with leucorrhea.
AB  - Bacteriological, Papanicolaou, direct immunofluorescense (DIF) and
      immunoperoxidase studies were done in 245 samples from women with vaginal
      discharge and the frequency of Chlamydia trachomatis was investigated. The
      samples were obtained from two hospitals of the Public Health Services of Mexico
      City. Samples were taken from the endocervical and posterior fornix areas and
      streaked in different cultures media for the isolation and microbiological
      differentiation. Smears were done and stained by Gram, Papanicolaou, DIF and
      immunoperoxidase techniques and the presence of cytological alterations and
      Chlamydia trachomatis was investigated. The microorganism was detected in 8
      patients by the three methods, only 4 of these were found by DIF, 7 by
      cytological and 6 by immunoperoxidase techniques. The infection caused by C.
      trachomatis cytologically was associated with mild or moderate dysplasia but not
      with some special microorganism.

PMID- 8986106
TI  - Biotypes of Gardnerella vaginalis isolated from urinary tract.
AB  - A modified scheme is proposed for biotyping Gardnerella vaginalis isolated from
      urinary tract of symptomatic and asymptomatic women based on detection of
      hippurate hydrolysis, beta-galactosidase (ONPG) and lipase, and fermentation of
      arabinose, galactose and xylose. Thirty biotypes were found among 73 strains. The
      distribution of biotypes was similar in both populations but the biotypes 1H, 5G
      and 7G were found more frequently in women without symptoms of urinary tract
      infection.

PMID- 8986108
TI  - Ciliatological characterization of a biological reactor that eliminates nitrogen
      with intermitent aeration.
AB  - Ciliates present in an activated sludge biological reactor used for removal of
      nitrogen compounds with intermitent aeration were determined. The reactor had a
      working volume of 30 liters, a hydraulic residence time of 20 hours, and a cell
      retention time of 15 days. Operating temperature was 15 degrees C, and it was fed
      with domestic sewage. Aeration was given in pulses, one hour aeration and one
      hour without aeration, feeding sodium acetate to favour denitrification
      processes. Elimination efficiency was 95% of the dissolved organic matter. During
      the pseudostable operating phase, 16 species of ciliates (Phylum Ciliophora) were
      found. They were distributed as follows: 13 Genera; 12 Families; 7 Orders; 6
      Subclasses; 5 Classes, and 3 Subphyla. From them, 9 are free swimmers and 7 are
      pedunculates. The Subphylum with higher diversity of species was the Ciliophora.
      The Oligohymenophorea Class was the best represented, corresponding to the
      Peritricha Subclass the highest number of species. Almost all the ciliates found
      have been reported as common inhabitants of activated sludge wastewater treatment
      plants with high removal efficiencies. They are catalogued as saprobe ciliates,
      within a and b masosaprobe levels. The presence of this ciliate community agrees
      with the carbon and nitrogen compounds removal efficiencies. Consequently, there
      exists the possibility of evaluating the operational efficiency of an
      aerobic/anoxic reactor using direct ciliates observations.

PMID- 8986109
TI  - Potency assay of diphtheria antitoxin in Vero cell microcultures.
AB  - Laboratory conditions were established for the titration of diphtheria toxin and
      antitoxin in Vero Cell Cultures (CCT) and a comparison was made with the
      intradermal test (IDT) as currently used throughout the world. Working dilutions
      and cut off values were established by reading both the change in color of phenol
      red used as pH indicator and changes in cell viability in the microscope. CCT
      shows high reproducibility and higher detectability than IDT in the titration of
      both WHO Reference Standard and high titer horse antisera. In sera of guinea pigs
      immunized for potency testing of diphtheria toxoid the titre was approximately 10
      times lower than in the IDT. The explanation is a subject of speculation. The
      Vero cell titration might be adopted as such for titration of diphtheria
      antitoxin. In the case of the toxoid potency test it could be used if the limit
      for the titration is adjusted to 0.2 IU considering the equivalence obtained
      between the two tests, by taking into account a ratio of 1:10 between CCT and
      IDT.

PMID- 8986107
TI  - Detection of Mycoplasma hominis and Ureaplasma urealyticum in women sexually
      active or not.
AB  - Genital mycoplasmas play an important role in genitourinary tract disease. The
      purpose of this study was to isolate M. hominis and U. urealyticum from vaginal
      and throat swabs and urine from women sexually active or not. Samples were taken
      from women with (cases) or without (controls) genitourinary tract disease and
      were dipped inoculated into 1 ml of E broth with arginine or urea and ten-fold
      dilutions were done. Samples were incubated at 37 degrees C until phenol red
      indicator changed to color purple. Identification of species was done by
      polymerase chain reaction technique. M. hominis was identified with
      oligonucleotides that correspond to the nucleotide sequence of 16S rRNA gene and
      U. urealyticum was identified with oligonucleotides that correspond to the
      nucleotide sequence of the urease gene (Blanchard et al.). There was no
      statistical difference (X2 P > .05) between isolation percentages from vaginal
      swabs, while there was statistical difference between urine samples. These
      mycoplasmas were isolated in higher percentages from pubertal girls and were
      recovered until the fifth ten-fold dilution both from vaginal swabs and urine.
      For throat swabs they were only recovered from sexually active women.

PMID- 8986111
TI  - Frequency of triatomines infected with Trypanosoma cruzi collected in Cuernavaca
      city, Morelos, Mexico.
AB  - In order to study the frequency of infection with Trypanosoma cruzi in the
      triatomines from Cuernavaca city (Morelos, Mexico), 1,060 triatomines were
      captured with the support of the population, from september 1990 to february
      1992; 1,035 were Triatoma pallidipennis adults, 88% presented flagellated
      protozoa with morphological characteristics corresponding to Trypanosoma spp.
      Later, in the laboratory, their ability to infect NIH mouse confirmed the
      isolates identities as Trypanosoma cruzi. The other 25 triatomines captured were
      adults of Triatoma barberi, 70% of them were infected with Trypanosoma cruzi. The
      results show the need to increase the study of the Chagas' disease in the urban
      and suburban areas as well as showing the need to provide further information to
      the population regarding the prevention of this parasitosis.

PMID- 8986110
TI  - Cryopreservation of infective larvae of Haemonchus contortus.
AB  - Three freeze protectants were evaluated to preserve H. contortus infective
      larvae. Freezing solutions used: A) saline solution phosphate buffer pH 7.2
      (PBS); B) 10% DMSO (dimethyl sulphoxide); C) 10% glycerol. Fifty thousand
      infective larvae were put into each of 10 vials per freeze protectant and then
      stored into liquid nitrogen. Results were based on the motility of the larvae
      under a light microscope at 30, 90, 180, and 360 days of freezing. Ten vials of
      each freeze protectant were removed from the liquid nitrogen at these times and
      immediately were put on water at 37 C during a minute. Motility percentages
      obtained were as follows: PBS: 36%, 20%, 7% and 39%; DMSO,: 87%, 69%, 46% and
      85%; glycerol: 67%, 62%, 29% and 55%; at 30, 90, 180 and 360 days respectively.
      Inoculation of infectiva larvae from DMSO and glycerol to calves was successful
      after 28 days. DMSO was a better freeze preserver for H. contortus.

PMID- 8986113
TI  - Diacetyl formation by lactic bacteria.
AB  - Some of the most widely used products in the food industry are flavour compounds.
      These products can be obtained either by chemical synthesis and therefore are
      called synthetic or by fermentation thus called natural flavors. There is a
      tendency towards the use of natural products by the consumer, therefore there is
      an increasing industrial interest in them. One of these products is diacetyl, an
      important component in the flavor of butter, although others, like acetoin,
      acetaldehyde and 2,3-butanediol play a role in the flavor, they are present in
      trace amounts. The mixture of all these compounds produced during the lactic acid
      fermentation in suitable proportions is what gives butter its characteristic
      flavor. The most common metabolic route that produces diacetyl is the one
      starting from pyruvate, in this case it seems that the biosynthesis is related to
      the presence of citrate in the medium. An alternative route for the production is
      from acetaldehyde, in this route citrate does not seem to intervene. In the
      present paper a review of the mechanisms of formation of diacetyl by lactic acid
      bacteria, as well as the most important factors that influence the biosynthesis
      of this metabolite is made.

PMID- 8986112
TI  - Antibody response to nitrogenase-positive and -negative Klebsiella pneumoniae
      strains in juvenile-onset ankylosing spondylitis patients and their first degree
      relatives: lack of differential recognition of the bacterial nitrogenase.
AB  - In the search for the pathogenic consequences of the molecular mimicry between
      the Klebsiella pneumoniae nitrogenase and the HLA-B27 antigen, sera from
      individuals belonging to 16 kindreds with juvenile-onset ankylosing spondylitis
      cases, were analyzed for antibodies against nitrogenase-positive and -negative K.
      pneumoniae whole bacterial extracts. An initial screening for nitrogenase
      producing K. pneumoniae strains was performed in 31 clinical isolates. The best
      nitrogenase producing strain was selected as well as a non producing one for
      immunoblot analysis using sera from 82 subjects, 55 HLA-B27 positive, of which 26
      had some clinical manifestations. Even though electrophoretic patterns were
      different in both strains, there was no distinctive differential recognition of
      the 30-40 kDa proteins where the nitrogenase subcomponent which shares the
      sequence QTDRED with the HLA-B27 molecule is located. On the other hand, strong
      recognition of a protein of 60 kDa (p60Kp) was detected in 75% of HLA-B27
      positive tested subjects independently of their clinical status. Studies on the
      nature of this protein and its participation in the pathogenesis of ankylosing
      spondylitis are now in progress.

PMID- 8986114
TI  - Rapid detection of factor V Leiden (FVQ506) by non-radioactive single strand
      conformation polymorphism (SSCP).
AB  - The transition G-->A at position 506 of the factor V gene is responsible for
      resistance to the anticoagulant effect of activated protein C (APC-resistance),
      and represents the most common hereditary risk factor for venous thrombosis. A
      comparison of the ability of non-radioactive single-strand conformation
      polymorphism (SSCP) and of a standard PCR procedure followed by further digestion
      with MnlI to detect this factor V gene (FVQ 506) transition indicates that these
      is a good agreement between the two methods. Non-radioactive SSCP analysis
      therefore represents a rapid and sensitive alternative for the diagnosis of this
      important point mutation.

PMID- 8986115
TI  - Kikuchi's disease: a case report with emphasis on flow cytometric studies.
AB  - We describe a case of 27 year-old female presenting with Kikuchi-Fujimoto's
      disease whose diagnosis was based on histopathologic and immunophenotypic
      studies. The illness was characterized by fever, urinary tract infections, skin
      rash, polyarthritis, generalized lymphadenopathy, pancytopenia, hepatic cytolysis
      and cholestasis, abnormal coagulation tests and elevated serum lactate
      dehydrogenase. The lymph node biopsy was consistent with the diagnosis of a
      histiocytic necrotizing lymphadenitis. Flow cyto-metric studies performed on the
      affected lymph node, bone marrow aspirate and peripheral blood, revealed a
      relative expansion of mature activated T lymphocytes, predominantly expressing a
      CD8 (+) phenotype.

PMID- 8986116
TI  - Association of cyclic peptides in aqueous solution measured by fluorescence
      quenching.

PMID- 8986117
TI  - Buckling transitions in superhelical DNA: dependence on the elastic constants and
      DNA size.
AB  - Buckling transitions in superhelical DNA are sudden changes in shape that
      accompany a smooth variation in a key parameter, such as superhelical density.
      Here we explore the dependence of these transitions on the elastic constants for
      bending and twisting. A and C, important characteristics of DNA's bending and
      twisting persistence lengths. The large range we explore extends to other elastic
      materials with self-contact interactions, modeled here by a Debye-Huckel
      electrostatic potential. Our collective description of DNA shapes and energies
      over a wide range of p = A/C reveals a dramatic dependence of DNA shape and
      associated configurational transitions on p: transitions are sharp for large p
      but masked for small p. In particular, at small p, a nonplanar circular family
      emerges, in agreement with Julicher's recent analytical predictions: a continuum
      of forms (and associated writhing numbers) is also observed. The relevance of
      these buckling transitions to DNA in solution is examined through studies of size
      dependence and thermal effects. Buckling transitions smooth considerably as size
      increases, and this can be explained in part by the lower curvature in larger
      plasmids. This trend suggests that buckling transitions should not be detectable
      for isolated (i.e., unbound) DNA plasmids of biological interest, except possibly
      for very large p. Buckling phenomena would nonetheless be relevant for small DNA
      loops, particularly for higher values of p, and might have a role in regulatory
      mechanisms: a small change in superhelical stress could lead to a large
      configurational change. Writhe distributions as a function of p, generated by
      Langevin dynamics simulations, reveal the importance of thermal fluctuations.
      Each distribution range (and multipeaked shape) can be interpreted by our
      buckling profiles. Significantly, the distributions for moderate to high
      superhelical densities are most sensitive to p, isolating different distribution
      patterns. If this effect could be captured experimentally for small plasmids by
      currently available imaging techniques, such results suggest a slightly different
      experimental procedure for estimating the torsional stiffness of supercoiled DNA
      than considered to date.

PMID- 8986119
TI  - Characterization of lipid membrane dynamics by simulation: I. Torsion angle
      motions of the linear chains.
AB  - The torsion angle motions, generated from molecular dynamics (MD) simulations, of
      the two aliphatic chains of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine
      (DMPC) in its lipid monolayer were evaluated by comparing these motions to those
      of an equivalent isolated (free) n-alkane chain, and the same n-alkane chain in
      its crystal lattice. The time-dependent autocorrelation and (1,2)-, (1,3)-, (1,4)
      , and (1,5)-cross-correlation functions were constructed to analyze the torsion
      angle motions. It was found that the torsion angle motions of the DMPC lipid
      monolayer aliphatic chains are intermediate to those of the free n-alkane chain
      and the same n-alkane chain in its crystal lattice, particularly for short
      correlation times. The torsion angle motions of the aliphatic chains of DMPC are
      also found to be essentially independent of the charge state on the head group.
      The linear aliphatic chains of a DMPC lipid monolayer behave most like the
      isolated n-alkane chains with respect to torsion angle flexibility, even though
      the pairs of aliphatic chains of each DMPC are part of an ordered monolayer
      assembly. The aliphatic chains of the DMPC molecules in their monolayer exhibit
      at least two types of wave motions. One of the wave motions is the same in form,
      though somewhat more diffuse, as a traveling wave found in n-alkane crystals. The
      other wave motion involves major torsion angle transitions, and has some
      characteristics of the soliton properties observed in n-alkane crystals near
      their respective melt transition temperatures.

PMID- 8986118
TI  - Lysine as helix C-capping residue in a synthetic peptide.
AB  - The structure of the synthetic peptide CH3CO(Leu-Ser-Leu-Leu-Leu-Ser-Leu)3Lys-NH2
      in trifluoroethanol/water 60/40 (volume ratio) was characterized by two
      dimensional nmr spectroscopy. The peptide, closely related to the amphiphilic
      helix models designed by W. F. De-Grado and co-workers to mimic protein ion
      channels [(1988) Science, Vol. 240, p. 1177-1181], folds into a regular helix
      spanning residues 1-20. Evidence for a helix C-terminal capping conformation,
      involving the terminal lysine residue, was observed from Overhauser effects and
      checked for consistency by restrained molecular dynamics simulations. The side
      chain amino group of Lys22 forms a hydrogen bond with the carbonyl of Leu18, and
      the distorted helical geometry of the terminal dipeptide allows the inclusion of
      a water bridge between the backbone NH of the Lys22 residue and the carbonyls of
      Leu19 and Ser20.

PMID- 8986120
TI  - The sensitivity of conformational free energies of the alanine dipeptide to
      atomic site charges.
AB  - Different atomic point charge sets are obtained for the alpha R and C7,eq
      conformations of the alanine dipeptide by fitting the charges of each
      conformation to the respective ab initio electrostatic potential surfaces both
      individually and simultaneously, in both the united atom and the all-atom
      representations. Using these charge sets, the sensitivity of the relative
      conformational aqueous free energies to the atomic site charges is investigated.
      For this particular system, we find that the solute-water contributions to the
      conformational free energy differences have a rather weak dependence on site
      charges; the calculated intramolecular contributions, however, show a rather
      strong dependence on the atomic site charges. It is suggested that the calculated
      results for the alanine dipeptide using a single, simultaneously fit set of
      charges for both conformations are in better agreement with experiments than the
      calculations carried out with charges determined individually for each
      conformation.

PMID- 8986121
TI  - Conformational analysis and molecular dynamics simulation of alpha-(1-->2) and
      alpha-(1-->3) linked rhamnose oligosaccharides: reconciliation with optical
      rotation and NMR experiments.
AB  - Molecular mechanics and dynamics calculations were carried out on the
      disaccharides alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->OMe) (1) and alpha-L-Rhap-(1
      ->3)-alpha-L-Rhap-(1-->OMe) (2), and the trisaccharide alpha-L-Rhap-(1-->2)-alpha
      L-Rhap-(1--> 3)-alpha-L-Rhap-(1-->OMe) (3). The semiflexible conformational
      behavior of these molecules was characterized by the occupation of a combination
      of different glycosidic linkage and side-chain conformational positions whose
      relative occupations were sensitive to dielectric screening. Molecular dynamics
      simulations of the trisaccharide 3 showed little difference between the linkage
      conformations in the trisaccharide and the component disaccharides 1 and 2
      Experimental optical rotation data of 1 and 2 were obtained as a function of
      temperature in varying solvents. The molecular models were combined with the
      semiempirical theory of Stevens and Sathyanarayana to yield calculated optical
      rotations. Interpretation of the data of both 1 and 2 implied that a combination
      of conformations, both in glycosidic and side-chain positions, could explain the
      experimental data. Solvents effects were important in influencing the
      conformational mix and averaged optical rotation. Three-bond heteronuclear
      coupling constants 3JC H were obtained for the glycosidic linkages of 1 and 2 in
      D2O and DMSO. Analysis of the coupling constants with a Karplus curve showed that
      small reductions in the glycosidic torsion angles of the conformations of the
      models used here of ca. 10 degrees-15 degrees in phi and 5 degrees-10 degrees in
      psi were required to give better agreement with experiment; a combination of
      conformations for both 1 and 2 was consistent with the data. There was a
      negligible influence on the coupling constants of 1 on changing the solvent from
      D2O to DMSO.

PMID- 8986122
TI  - Design of specific structures using alpha,beta-dehydro-phenylalanine residues:
      synthesis, crystal structure, and molecular conformation of Boc-L-Val-delta Phe
      delta Phe-L-Val-delta Phe-delta Phe-L-Val-OCH3, a 3(10)-helical heptapeptide.
AB  - The peptide design using alpha,beta-dehydro-residues has wide applications. To
      design an extensive 3(10)-helical conformation, a heptapeptide Boc-L-Val-delta
      Phe-delta Phe-L-Val-delta Phe-delta Phe-L-Val-OCH3, with a repeat of two
      consecutive delta Phe residues has been synthesized using an azlactone method in
      solution phase. This is the first design using a repeat of two consecutive delta
      Phe residues. It is observed that the delta Phe in a sequence of two consecutive
      delta Phe residues, adopts only one set of phi, psi values, i.e., +/- 60 degrees,
      +/- 30 degrees, thus making it a specific design tool. The peptide crystallized
      from its solution in a methanol-water mixture in the space group P2(1) with a =
      10.159(5)A, b = 20.057(2)A, c = 14.448(3)A, beta = 99.41(2)degrees, V =
      2904(2)A3. The structure has been determined by direct methods and refined to an
      R value of 0.048 for 5404 observed [I > or = 3 sigma(I)] reflections. The
      structure consists of a heptapeptide Boc-L-Val-delta Phe-delta Phe-L-Val-delta
      Phe-delta Phe-L-Val-OCH3 and a solvent methanol molecule in the asymmetric unit.
      All peptide units in the structure are trans. As a result of six overlapping type
      III beta-turns formed involving seven residues and five intramolecular 4-->1
      hydrogen bonds, the peptide adopts a right-handed 3(10)-helical conformation with
      more than two complete helical turns. It is noteworthy that starting from the Boc
      group to the C-terminal residue of Val, the 3(10)-helical structure is maintained
      well. The carbonyl oxygen atom of the Boc group is the first acceptor whereas the
      carbonyl oxygen atom of Val4 is the last acceptor in the helical structure of the
      peptide. The side chains of four delta Phe residues in this helical arrangement
      exist in a slightly staggered arrangement. The solvent methanol molecule
      interacts through its hydroxyl group and forms two intermolecular hydrogen bonds,
      one as a donor with a C-terminal CO group of delta Phe6 and second as an acceptor
      with the NH group of delta Phe2 from the N-terminal region of the peptide. Thus
      the solvent molecule plays a significant role in promoting a head-to-tail packing
      of 3(10)-helices of the peptide. There are no lateral hydrogen bonds between the
      helices, but there exist several van der Waals interactions involving the
      hydrophobic side chains of peptide molecules.

PMID- 8986123
TI  - Modeling the DNA-solvent interface.
AB  - We extend the technique of using perpendicular distribution functions to salt
      solutions around nucleic acids. Both solute density averaged and nonaveraged
      reference frames are considered and compared. Using a previous simulation of DNA
      in salt water of over a nanosecond in duration, the aqueous distribution
      functions were found to be well coveraged, whereas the salt perpendicular
      distribution functions were less well determined. Three-dimensional density
      reconstructions reliably showed the prominent solvation features with
      transferable functions. The number of solute atom types needed for
      reconstructions of a given precision was determined in the context of the
      reference simulation data set with the goal of achieving a required level of
      reconstruction quality.

PMID- 8986124
TI  - Genetic relatedness of North American populations of Tomicus piniperda
      (Coleoptera:Scolytidae).
AB  - We used DNA fingerprinting by random amplified polymorphic (RAPD) DNA and
      electrophoretic characterization of esterase isozymes to investigate the genetic
      relatedness of North American populations of the exotic bark beetle Tomicus
      piniperda (L.). Cluster analyses of genetic distances among populations
      identified the Illinois population as an outlier population with mean genetic
      distances to other populations averaging 0.895 (where complete dissimilarity =
      2), compared with genetic distance averages of 0.595 among populations excluding
      Illinois. When genetic distance means and geographical distance between
      populations were compared, the results suggested that T. piniperda populations in
      the United States were established separately in Illinois near Lake Michigan and
      in Ohio along Lake Erie. Molecular markers indicated that insects derived from
      the 2 founder groups were interbreeding in contiguous regions in western Indiana.

PMID- 8986125
TI  - Alfalfa weevil (Coleoptera:Curculionidae) management in alfalfa by spring grazing
      with cattle.
AB  - The effect of continuous, intensive grazing by cattle in the 1st alfalfa growth
      cycle on larval densities of the alfalfa weevil, Hyera postica (Gyllenhal), was
      evaluated in "Alfagraze' and "Apollo' alfalfa, which are tolerant and not
      tolerant to grazing, respectively. In small-cage exclusion trials, grazing
      reduced larval numbers in 1991 by 65% in Alfagraze and by 32% in Apollo. Larval
      numbers in 1992 were low (< or = 0.6 larvae per stem) and were not reduced
      significantly by grazing. Grazing and use of early insecticide treatments of
      permethrin or carbofuran at low rates with < or = 7-d grazing restrictions to
      suppress larval numbers before grazing also were examined in large-plot exclusion
      trails in 1993 and 1994. Grazing reduced larval densities by 60% in 1993 and 45%
      in 1994 during a 3-wk period beginning 3 wk after grazing was initiated. However,
      alfalfa weevil larvae caused moderate leaf injury in 1993 and severe injury in
      1994 before grazing reduced larval numbers. Use of permethrin at 0.11 kg (AI)/ha
      or carbofuran or chlorpyrifos at 0.28 kg (AI)/ha effectively reduced larval
      numbers and prevented leaf injury before grazing began. Therefore, a combination
      of an early application of an insecticide treatment with a short grazing
      restriction followed by continuous grazing will control alfalfa weevil larvae
      while allowing cattle to graze and directly use forage of grazing-tolerant
      alfalfa.

PMID- 8986126
TI  - Functional consequences of the phosphorylation of the gonadotropin receptors.
AB  - When target cells are exposed to a hormone, their responsiveness wanes with time,
      in spite of the continuous presence of the hormone. This phenomenon, referred to
      as desensitization, is due to regulatory steps that occur at the level of the
      hormone receptor as well as at post-receptor steps. While post-receptor events
      may be specific for the metabolic pathways activated in a given target cell,
      receptor events are more general in nature and conserved within a given family of
      receptors. There are at least two categories of regulatory events that occur at
      the level of the receptor and contribute to the process of desensitization. One
      of them, referred to as receptor uncoupling, will be used here to denote a change
      in the functional properties of a constant number of receptors resulting in a
      reduction in the ability of the receptor to activate its most proximal effector
      system. The other, referred to as receptor down-regulation, will be used here to
      denote a reduction in the density of cell surface receptors. Uncoupling is
      generally faster than down-regulation, and is believed to be due to post
      translational modifications of the receptor. Down-regulation, on the other hand,
      is slower, and could be due to an increase in the rate of receptor
      internalization, sequestration or degradation, and/or to a decrease in the rate
      of receptor externalization, processing or synthesis. In this paper, recent
      studies from my laboratory designed to directly address the potential involvement
      of gonadotropin receptor phosphorylation in the process of uncoupling have been
      reviewed.

PMID- 8986127
TI  - Mitochondrial respiratory enzyme function and superoxide dismutase activity
      following brain glutathione depletion in the rat.
AB  - In substantia nigra from patients with Parkinson's disease, there are decreased
      levels of reduced glutathione (GSH) and diminished activities of mitochondrial
      complex I and alpha-ketoglutarate dehydrogenase (alpha-KGDH), along with
      increased activity of superoxide dismutase (SOD). However, the interrelationship
      among these events is uncertain. We now report the effect of decreased brain GSH
      levels on SOD and mitochondrial respiratory enzyme activity in rat brain. In
      addition, we have investigated the ability of thioctic acid, an endogenous
      antioxidant, to alter these parameters. Unilateral or bilateral
      intracerebroventricular (ICV) administration of buthionine sulphoximine (BSO; 1 x
      3.2 mg or 2 x 1.6 mg) over a 48-hr period reduced cortical GSH by 55-70%. There
      was no change in the activity of complex I, II/III, or IV or of citrate synthase
      in cortex. Similarly, there was no alteration of mitochondrial or cytosolic SOD
      activity. Thioctic acid (50 or 100 mg/kg IP) alone had no effect on cortical GSH
      levels in control animals and did not reverse the decrease in GSH levels produced
      by unilateral or bilateral ICV BSO administration. Thioctic acid (50 or 100 mg/kg
      IP) had no overall effect on complex I, II/III, or IV or on citrate synthase
      activity in control animals. Thioctic acid also did not alter cortical
      mitochondrial respiratory enzyme activity in BSO-treated rats. At the lower dose,
      thioctic acid tended to increase mitochondrial and cytosolic SOD activity in
      control animals and in BSO-treated rats. However, at the higher dose, thioctic
      acid tended to decrease mitochondrial SOD activity. Overall, there was no
      consistent effect of thioctic acid (50 or 100 mg/kg IP) on SOD activity in
      control or BSO-treated animals. This study shows that BSO-induced glutathione
      deficiency does not lead to alterations in mitochondrial respiratory enzyme
      activity or to changes in SOD activity. GSH depletion in Parkinson's disease
      therefore may not account for the alterations occurring in complex I and
      mitochondrial SOD in substantia nigra. Thioctic acid did not alter brain GSH
      levels or mitochondrial function. Interestingly, however, it did produce some
      alterations in SOD activity, which may reflect either its antioxidant activity or
      its ability to act as a thiol-disulphide redox couple.

PMID- 8986128
TI  - Evidence for posttranscriptional regulation of GLUT4 expression in muscle and
      adipose tissue from streptozotocin-induced diabetic and benfluorex-treated rats.
AB  - In this study we explored the expression of GLUT4 glucose carriers in muscle and
      adipose tissues from streptozotocin-induced diabetic and benfluorex-treated rats.
      In nondiabetic rats, benfluorex treatment decreased GLUT4 protein content in
      muscle and brown adipose tissue, with no change in GLUT4 mRNA. This effect
      occurred in the presence of normal circulating levels of insulin and glucose.
      Seventeen days after streptozotocin injection, diabetic rats showed a decreased
      GLUT4 protein content in adipose tissues and in both red and white skeletal
      muscle. Diabetic rats showed decreased GLUT4 mRNA levels in white and brown
      adipose tissue, whereas messenger concentrations remained unaltered in red and
      white fibers of skeletal muscle. The interaction of benfluorex and diabetes on
      GLUT4 protein expression showed a tissue-specific pattern. Benfluorex treatment
      to some extent prevented the decrease in GLUT4 protein in white and brown adipose
      tissue and in white muscle associated with diabetes. In contrast, diabetes and
      benfluorex caused an additive decrease in GLUT4 expression in red skeletal
      muscle. The effects of benfluorex on GLUT4 content in tissues from diabetic rats
      occurred in the absence of alterations in GLUT4 mRNA levels, suggesting a
      modification of translational or posttranslational steps. Benfluorex did not
      ameliorate the hyperglycemia of diabetic rats. Our results indicate that red and
      white skeletal muscle respond to diabetes and benfluorex in a heterogeneous
      manner, which suggests the existence of differences in the mechanisms that
      regulate GLUT4 expression. Furthermore, our data indicate that GLUT4 expression
      in muscle and adipose tissue can be regulated by modification of translational or
      posttranslational steps.

PMID- 8986129
TI  - Amsacrine-promoted DNA cleavage site determinants for the two human DNA
      topoisomerase II isoforms alpha and beta.
AB  - Site-specific DNA cleavage by topoisomerase II (EC 5.99.1.3) is induced by many
      antitumour drugs. Although human cells express two genetically distinct
      topoisomerase II isoforms, thus far the role and determinants of drug-induced DNA
      cleavage have been examined only for alpha. Here we report the first high
      resolution study of amsacrine (mAMSA) induced DNA breakage by human topoisomerase
      II beta (overexpressed and purified from yeast) and a direct comparison with the
      recombinant alpha isoform. DNA cleavage in plasmid pBR322 and SV40 DNA was
      induced by alpha or beta in the absence or presence of the antitumour agent
      mAMSA, and sites were mapped using sequencing gel methodology. Low-resolution
      studies indicated that recombinant human alpha promoted DNA breakage at sites
      akin to those of beta, although some sites were only cleaved by one enzyme and
      different intensities were observed at some sites. However, statistical analysis
      of 70 drug-induced sites for beta and 70 sites for alpha revealed that both
      isoforms share the same base preferences at 13 positions relative to the enzyme
      cleavage site, including a very strong preference for A at +1. The result for
      recombinant alpha isoform is in agreement with previous studies using alpha
      purified from human cell lines. Thus, alpha and beta proteins apparently form
      similar ternary complexes with mAMSA and DNA. Previous studies have emphasized
      the importance of DNA topoisomerase II alpha; the results presented here
      demonstrate that beta is an in vitro target with similar site determinants,
      strongly suggesting that beta should also be considered a target of mAMSA in
      vivo.

PMID- 8986130
TI  - The crucial antioxidant action of schisandrin B in protecting against carbon
      tetrachloride hepatotoxicity in mice: a comparative study with butylated
      hydroxytoluene.
AB  - A comparison between the effects of schisandrin B (Sch B) and butylated
      hydroxytoluene (BHT) treatments on hepatic antioxidant status was made to
      identify the critical antioxidant action of Sch B involved in hepatoprotection in
      mice. Whereas Sch B treatment (3 mmol/kg/day x 3, p.o.) increased the hepatic
      mitochondrial-reduced glutathione (GSH) level, BHT treatment at the same dosage
      regimen decreased it. However, both Sch B and BHT increased, albeit to a
      different extent, the activity of mitochondrial glutathione reductase. The
      differential effect of Sch B and BHT treatment on hepatic mitochondrial
      glutathione status became more apparent after carbon tetrachloride (CCl4)
      challenge. Pretreatment with Sch B could sustain the hepatic mitochondrial GSH
      level in CCl4-intoxicated mice and protect against CCl4 hepatotoxicity. BHT
      pretreatment did not produce any protective effect on CCl4-induced GSH depletion
      in mitochondrion and hepatocellular damage. Although both Sch B and BHT
      treatments increased hepatic ascorbic acid (VC) level in control animals, only
      Sch B pretreatment sustained a high hepatic VC level in CCl4-intoxicated mice.
      Moreover, Sch B pretreatment prevented the CCl4-induced decrease in the hepatic
      alpha-tocopherol (VE) level. However, Sch B inhibited NADPH oxidation in mouse
      liver microsomes incubated with CCl4 in vitro, whereas BHT stimulated this
      oxidation. The ensemble of results suggests that the ability to sustain the
      hepatic mitochondrial GSH level and the hepatic VC and VE levels may represent
      the crucial antioxidant action of Sch B in protection against CCl4
      hepatotoxicity. The possible inhibition of CCl4 metabolism by Sch B may also
      contribute to its hepatoprotective action.

PMID- 8986131
TI  - Expression of laminin and type IV collagen by basement membrane-producing EHS
      tumors in streptozotocin-induced diabetic mice: in vivo modulation by low
      molecular-weight heparin fragments.
AB  - The biosynthesis of basement membrane components in Engelberth Holm Swarm-bearing
      mice with or without streptozotocin-induced diabetes and the effect of low
      molecular-weight heparin derivatives (CY222, Sanofi Recherche/Institut Choay) on
      the relative rates of these synthetic activities were studied. In diabetic mice,
      the laminin mRNA level increased, whereas type IV collagen mRNA decreased. In
      vivo treatment with heparin fragments decreased the mRNA level of laminin to
      control values without altering the mRNA level of collagen IV. Biosynthetic
      studies with radiolabeled precursors ([3H]-proline for collagen and [35S]
      methionine for laminin) confirmed these results. Laminin protein biosynthesis
      increased in diabetic mice. Treatment with CY222 corrected this alteration. Our
      results suggested an increased labeling of polymeric forms of collagen IV in
      diabetic mice. In addition, we showed that biosynthesis of acid-extractable
      collagen IV decreased in diabetic mice and that CY222 treatment corrected this
      disturbance. These experiments suggest that low-molecular-weight heparin
      fragments CY222 can modulate the biosynthesis of extracellular matrix
      macromolecules altered in diabetic animals by different pathways, including
      pretranslational and posttranslational steps.

PMID- 8986133
TI  - Bioreductive activation of a series of analogues of 5-aziridinyl-3-hydroxymethyl
      1-methyl-2-[1H-indole-4, 7-dione] prop-beta-en-alpha-ol (EO9) by human DT
      diaphorase.
AB  - The enzyme DT-diaphorase (NAD(P)H:quinone acceptor oxidoreductase, EC 1.6.99.2.;
      DTD) is believed to be a good target for enzyme-directed bioreductive drug
      development because elevated levels of enzyme activity have been described in
      several human tumour types and it plays a key role in the bioreductive activation
      of several quinone-based anticancer drugs. As part of an ongoing program to
      develop new bioreductive drugs, the ability of a series of indoloquinone
      compounds to serve as substrates for and to be bioreductively activated by
      purified recombinant human DTD was investigated. Of the seven compounds
      evaluated, EO9, EO68 and EO4 were substrates for human DTD, but only EO4 was
      reduced to a DNA cross-linking species, and this DNA damage was both
      concentration dependent and inhibited by dicoumarol. A broad spectrum of
      chemosensitivity was observed in the H460 non-small cell lung cancer cell line,
      with the most potent compounds being EO4 (IC50 = 23.9 nM), EO9 (IC50 = 34.5 nM)
      and EO68 (IC50 = 37.8 nM). Relatively minor structural changes resulted in major
      changes in both substrate specificity and cytotoxic potency. Comparative
      chemosensitivity studies demonstrated that EO4, EO9 and EO68 are preferentially
      toxic towards DTD-rich H460 cells compared with DTD-deficient H596 cells (ratio
      of IC50 values for H596 cells to H460 cells were 113.8, 92.2 and 103.9
      respectively). In conclusion, this study has identified two new compounds that
      are substrates for human DTD, one of which (EO4) is reduced to a DNA cross
      linking species. Further studies in a broad panel of cell lines and human tumour
      xenografts are warranted for EO4 and EO68 based upon the result of this study.

PMID- 8986132
TI  - Ebselen and cytokine-induced nitric oxide synthase expression in insulin
      producing cells.
AB  - Interleukin-1 (IL-1) may be a mediator of beta-cell damage in insulin-dependent
      diabetes mellitus (IDDM). The IL-1 mechanism of action on insulin-producing cells
      probably includes activation of the transcription nuclear factor kappa B (NF
      kappa B), increased transcription of the inducible form of nitric oxide synthase
      (iNOS) and the subsequent production of nitric oxide (NO). Reactive oxygen
      intermediates, particularly H2O2, have been proposed as second messengers for NF
      kappa B activation. In the present study, we tested whether ebselen (2-phenyl-1,2
      benzisoselenazol-3(2H)-one), a glutathione peroxidase mimicking compound, could
      counteract the effects of IL-1 beta, H2O2 and alloxan in rat pancreatic islets
      and in the rat insulinoma cell line RINm5F (RIN cells). Some of these experiments
      were also reproduced in human pancreatic islets. Ebselen (20 microM) prevented
      the increase in nitrite production by rat islets exposed to IL-1 beta for 6 hr
      and induced significant protection against the acute inhibitory effects of
      alloxan or H2O2 exposure, as judged by the preserved glucose oxidation rates.
      However, ebselen failed to prevent the increase in nitrite production and the
      decrease in glucose oxidation and insulin release by rat islets exposed to IL-1
      beta for 24 hr. Ebselen prevented the increase in nitrite production by human
      islets exposed for 14 hr to a combination of cytokines (IL-1 beta, tumor necrosis
      factor-alpha and interferon-gamma). In RIN cells, ebselen counteracted both the
      expression of iNOS mRNA and the increase in nitrite production induced by 6 hr
      exposure to IL-beta but failed to block IL-1 beta-induced iNOS expression
      following 24 hr exposure to the cytokine. Moreover, ebselen did not prevent IL-1
      beta-induced NF-kappa B activation. As a whole, these data indicate that ebselen
      partially counteracts cytokine-induced NOS activation in pancreatic beta-cells,
      an effect not associated with inhibition of NF-kappa B activation.

PMID- 8986134
TI  - The effect of prolactin on casein kinase II, MAP kinase and PKC in rabbit mammary
      cells and Nb2 rat lymphoid cells.
AB  - Prolactin induces milk protein gene expression in rabbit primary mammary cells
      without any concomitant cell multiplication. Prolactin or other lactogenic
      hormones is the major inducer of cell division in the rat lymphoid Nb2 cells. In
      Nb2 cells, prolactin also rapidly induces the expression of the c-myc gene, and
      beta-actin and stathmin gene expression is induced more slowly. The possible
      involvement of casein kinase II (CKII), mitogen-activated protein kinase (MAPK)
      and protein kinase C (PKC) in these process is not well known. The present work
      was undertaken to evaluate the effect of prolactin on these protein kinases and
      to determine the possible involvement of these enzymes in the activity of several
      genes under the control of the hormone. In rabbit mammary cells, prolactin did
      not alter CKII activity but did transiently stimulate MAP kinase activity.
      Prolactin also stimulated Ca(2+)-independent PKC. This effect was visible after
      10 min and was maintained for at least 24 hr. Staurosporine, an inhibitor of PKC
      and of several tyrosine kinases altered Ca(2+)-independent PKC only moderately.
      In contrast, GF 109203X, a potent and specific inhibitor of PKC, abrogated almost
      all PKC activity. Staurosporine, but not GF 109203X, prevented the induction of
      the casein gene by prolactin. In Nb2 cells, prolactin induced a slow stimulation
      of CKII activity. The hormone did not induce MAP kinase activity. Prolactin
      stimulated Ca(2+)-independent PKC over periods of 24 hr. GF 109203X, but not
      staurosporine, inhibited PKC activity, whereas staurosporine but not GF 109203X,
      inhibited the induction of Nb2 cell multiplication and the accumulation of c-myc,
      beta-actin and stathmin mRNAs. From these data, it can be concluded that (1) the
      stimulation of CKII by prolactin in Nb2 cells is concomitant with cell
      multiplication: (2) MAPK stimulation is not necessary for prolactin to induce Nb2
      cell multiplication; and (3) PKC is stimulated in mammary and Nb2 cells, but this
      stimulation is not required for prolactin to stimulate casein, c-myc, beta-actin
      and stathmin gene expression and Nb2 cell division.

PMID- 8986135
TI  - DNA repair in cisplatin-sensitive and resistant human cell lines measured in
      specific genes by quantitative polymerase chain reaction.
AB  - More than 80% of patients with testicular germ cell tumours (TGCT) are cured
      using cisplatin-based combination chemotherapy, and resistance to cisplatin is
      the final barrier to the cure of nearly all patients with this disease. In this
      study, we used quantitative polymerase chain reaction (Q-PCR) to investigate the
      role of DNA repair in cisplatin resistance in two genes, one transcribed and one
      not transcribed. Three pairs of cisplatin-sensitive and resistant cell lines were
      used, two derived from TGCT and one from a bladder cancer. In these pairs of
      sublines, we observed no major differences between the repair of cisplatin
      induced damage in the transcribed and nontranscribed genes, nor did there appear
      to be any relationship between DNA repair capacity and the development of
      cisplatin resistance. Despite the strong indication that the sensitivity of
      testis tumour cells to cisplatin is related to their reduced ability to repair
      cisplatin-damaged DNA, these cells apparently do not become resistant to
      cisplatin by acquiring DNA repair capacity.

PMID- 8986136
TI  - Stimulation of protein synthesis by phosphatidic acid in rat cardiomyocytes.
AB  - Phosphatidic acid (PA) was observed to stimulate protein synthesis in adult
      cardiomyocytes in a time- and concentration-dependent manner. The maximal
      stimulation in protein synthesis (142 +/- 12% vs 100% as the control) was
      achieved at 10 microM PA within 60 min and was inhibited by actinomycin D (107 +/
      4% of the control) or cycloheximide (105 +/- 6% of the control). The increase in
      protein synthesis due to PA was attenuated or abolished by preincubation of
      cardiomyocytes with a tyrosine kinase inhibitor, genistein (94 +/- 9% of the
      control), phospholipase C inhibitors 2-nitro-4-carboxyphenyl N,N-diphenyl
      carbamate or carbon-odithioic acid O-(octahydro-4,7-methanol-1H-inden-5-yl (101
      +/- 6 and 95 +/- 5% of the control, respectively), protein kinase C inhibitors
      staurosporine or polymyxin B (109 +/- 3 and 93 +/- 3% of the control), and
      chelators of extracellular and intracellular free Ca2+ EGTA or BAPTA/AM (103 +/-
      6 and 95 +/- 6% of the control, respectively). PA at different concentrations
      (0.1 to 100 microM) also caused phosphorylation of a cell surface protein of
      approximately 24 kDa. In addition, mitogen-activated protein kinase was
      stimulated by PA in a concentration-dependent manner; maximal stimulation (217 +/
      6% of the control) was seen at 10 microM PA. These data suggest that PA
      increases protein synthesis in adult rat cardiomyocytes and thus may play an
      important role in the development of cardiac hypertrophy.

PMID- 8986137
TI  - Oxidative inactivation of thioredoxin as a cellular growth factor and protection
      by a Cys73-->Ser mutation.
AB  - Thioredoxin (Trx) is a widely distributed redox protein that regulates several
      intracellular redox-dependent processes and stimulates the proliferation of both
      normal and tumor cells. We have found that when stored in the absence of reducing
      agents, human recombinant Trx undergoes spontaneous oxidation, losing its ability
      to stimulate cell growth, but is still a substrate for NADPH-dependent reduction
      by human thioredoxin reductase. There is a slower spontaneous conversion of Trx
      to a homodimer that is not a substrate for reduction by thioredoxin reductase and
      that does not stimulate cell proliferation. Both conversions can be induced by
      chemical oxidants and are reversible by treatment with the thiol reducing agent
      dithiothreitol. SDS-PAGE suggests that Trx undergoes oxidation to monomeric
      form(s) preceding dimer formation. We have recently shown by X-ray
      crystallography that Trx forms a dimer that is stabilized by an intermolecular
      Cys73-Cys73 disulfide bond. A Cys73-->Ser mutant Trx (C73S) was prepared to
      determine the role of Cys73 in oxidative stability and growth stimulation. C73S
      was as effective as Trx in stimulating cell growth and was a comparable substrate
      for thioredoxin reductase. C73S did not show spontaneous or oxidant-induced loss
      of activity and did not form a dimer. The results suggest that Trx can exist in
      monomeric forms, some of which are mediated by Cys73 that do not stimulate cell
      proliferation but can be reduced by thioredoxin reductase. Cys73 is also involved
      in formation of an enzymatically inactive homodimer, which occurs on long term
      storage or by chemical oxidation. Thus, although clearly involved in protein
      inactivation, Cys73 is not necessary for the growth stimulating activity of Trx.

PMID- 8986138
TI  - Discordant expression of the cyclin-dependent kinases and cyclins in rat liver
      following acute administration of the hepatocarcinogen [4-chloro-6-(2,3-xylidino)
      2-pyrimidinylthio] acetic acid (WY14,643).
AB  - Cellular proliferation is an essential aspect of chemical carcinogenesis. At the
      core of cell cycle regulation is a family of serine/threonine protein kinases
      termed cyclin-dependent kinases (cdk). Cdk activity, which directs progression
      through the cell cycle, is dependent upon cdk binding to the appropriate, phase
      specific cyclin proteins. Alterations in hepatic cdk1, cdk2, cdk4, cdk5, and
      cyclin protein expression were determined in response to acute dosing of the
      prototypic peroxisome proliferator and hepatocarcinogen [4-chloro-6-(2,3
      xylidino)-2-pyrimidinylthio] acetic acid (WY14,643). Intraperitoneal dosing of 45
      mg WY14,643/kg daily for 4 days to young, male rats produced dramatic increases
      in hepatic protein expression of all cdk analyzed as well as cyclins B, D2, D3,
      and proliferating cell nuclear antigen (PCNA). The largest relative increases,
      6.1-, 2.8-, 11-, 83-, and 7.9-fold, were seen with cdk1, cdk4, cyclin B, cyclin
      D3, and PCNA, respectively. Increases of only 1.8-, 2-, 1.6-, and 1.4-fold were
      noted, respectively, for cdk2, cdk5, cyclin D2, and cyclin E. Analysis of gel
      filtration fractions indicated that PCNA co-eluted with cdk1 from the WY14,643
      treated rats as a 70-80 kDa molecular complex. In contrast, cdk4, cdk5 and D
      cyclins migrated as much larger complexes with an estimated MW of approximately
      180-190 kDa.

PMID- 8986139
TI  - Effect of deoxycoformycin and Val-boroPro on the associated catalytic activities
      of lymphocyte CD26 and ecto-adenosine deaminase.
AB  - CD26 and ecto-adenosine deaminase (ADA) are found associated on the plasma
      membrane of T lymphocytes and each possess distinct catalytic activities. CD26
      has a proteolytic activity identical to dipeptidylpeptidase IV (DPPIV; E.C.
      3.4.14.5), and ecto-ADA (E.C. 3.5.4.4) degrades extracellular adenosine. The cell
      surface expression of CD26 and ecto-adenosine deaminase (ecto-ADA) is regulated
      on stimulated T lymphocytes, and ADA binding to CD26 produces a synergistic
      costimulatory response with T cell receptor activation. This study addresses the
      potential regulation by allosteric interactions of the catalytic activities of
      CD26 associated with ecto-ADA, which could define the mechanism of the synergism
      observed in T cell signaling. Cell lines genetically deficient in ADA, ligands
      for ADA such as adenosine, and a specific inhibitor of ADA, deoxycoformycin, were
      used to define the effect of ADA activity on CD26 DPPIV activity and affinity for
      dipeptide substrate. Conversely, a recombinant Chinese hamster ovary cell line
      expressing human CD26 with or without a mutation in the DPPIV catalytic domain,
      and the boronic acid inhibitor Val-boroPro, were used to determine the effect of
      DPPIV activity on ecto-ADA activity and association with CD26. These studies
      found no significant allosteric interaction between the catalytic activities of
      CD26 and ecto-ADA when associated. Therefore, signaling events in T cells
      involving costimulation with CD26 and ecto-ADA and the synergism observed upon
      ADA binding to CD26 occur independently of the catalytic activities of these cell
      surface molecules.

PMID- 8986140
TI  - Allosteric regulation of the binding of [3H]acetylcholine to m2 muscarinic
      receptors.
AB  - Muscarinic receptors of the m2 subtype expressed in Chinese hamster ovary cells
      were labeled with [methyl-3H]acetylcholine([3H]ACh), and the rate of dissociation
      in the presence and absence of several compounds known to exert allosteric
      effects on labeled antagonist binding was observed. At 25 degrees C, [3H]ACh
      bound to the receptors with a Kd of 1.2 nM and dissociated with a half-time of
      1.6 min. This binding was sensitive to appropriate concentrations of guanine
      nucleotide and the muscarinic antagonist N-methylscopolamine (NMS). Gallamine,
      tetrahydroaminoacridine, physostigmine, obidoxime, and 3,4,5-trimethoxybenzoic
      acid 8-(diethylamino)octyl ester (TMB-8) all inhibited the binding of [3H]ACh and
      all slowed the rate of dissociation of [3H]ACh in a concentration-dependent
      manner. However, the nature of some of the allosteric effects differed from
      previous studies that used other labeled ligands. In particular, TMB-8, which is
      very effective in slowing the dissociation of the antagonist [3H]NMS, had much
      weaker effects on the dissociation of [3H]ACh. Furthermore, TMB-8 was able to
      partially reverse the stronger effects of gallamine on the dissociation of
      [3H]ACh, consistent with the possibility that TMB-8 and gallamine share a common
      site on the receptor. In summary, the binding of ACh to muscarinic receptors is
      subject to allosteric regulation, and assays using [3H]ACh may be especially
      useful in the evaluation of potential allosteric regulators of muscarinic
      systems.

PMID- 8986141
TI  - Selective inhibition of cyclooxygenase-1 and -2 using intact insect cell assays.
AB  - We have utilized the baculovirus expression system to develop an in vitro intact
      cell assay for screening nonsteroidal anti-inflammatory drug (NSAID) inhibition
      of the two isozymes of human cyclooxygenase (prostaglandin endoperoxidase
      synthase, EC 1.14.99.1). Infected Spodoptera frugiperda (sf9) cells expressing
      either human cyclooxygenase-1 (hCOX-1) or human cyclooxygenase-2 (hCOX-2) were
      harvested 24 hr postinfection, a time point where all cells are viable and hCOX-1
      or hCOX-2 are correctly processed. Cells were distributed to a 96-well plate,
      preincubated with various NSAIDs, and challenged with 10 microM arachidonic acid;
      then cyclooxygenase activity was assessed indirectly by prostaglandin E2-specific
      radioimmunoassay. The rank order of potency of NSAID-mediated inhibitions of hCOX
      1 and hCOX-2 paralleled those that have been observed in other cell systems. This
      sf9 cell-based assay can be utilized for the identification of potent and
      selective inhibitors of hCOX-1 and/or hCOX-2. Compounds that preferentially
      inhibit hCOX-2 may provide novel NSAIDs that reduce inflammation while sparing
      the stomach and kidneys of toxic side-effects seen with current nonselective
      NSAIDs.

PMID- 8986142
TI  - Analysis of structural requirements for Ah receptor antagonist activity:
      ellipticines, flavones, and related compounds.
AB  - A number of studies have examined the structure-activity relationships for the
      agonist activity of Ah receptor (AhR) ligands. Fewer studies have considered the
      structural basis for potential antagonist properties. Certain ellipticine
      derivatives have been reported to bind to the AhR and inhibit the ability of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to transform the AhR to a form that
      recognizes a dioxin-responsive enhancer element (DRE) upstream of the cytochrome
      P4501A1 gene. In the present study, over 30 ellipticine derivatives and
      structurally related compounds were examined for their ability to bind to the
      AhR, activate it to a DRE-binding form, induce the luciferase gene under control
      of a DRE-containing enhancer, and block activation of the AhR by TCDD. The
      ability of several ellipticine derivatives to inhibit TCDD-elicited DRE binding
      and TCDD-induced luciferase activity was inversely related to their ability to
      alone stimulate these responses. The most potent antagonist activity was related
      to good AhR binding characteristics in terms of conforming to previously
      predicted 14 x 12 x 5 A van der Waals dimensions and the presence of an electron
      rich ring nitrogen at or near a relatively unsubstituted X-axis terminal
      position. Based on these data, a number of flavone derivatives were synthesized
      and tested for their relative agonist/antagonist activity. These additional data
      were consistent with the hypothesis that an electron-rich center near or along a
      lateral position of the van der Waals binding cavity is a characteristic that
      enhances AhR antagonist activity.

PMID- 8986143
TI  - Screening for neuroblastoma in France: methodological aspects and preliminary
      observations.
AB  - A pilot study of neuroblastoma mass screening was initiated in January 1990 in
      the Rhone French district. The expected number of births per year is 26,000. The
      study is designed for a 5-year period with three major goals: 1) measurement of
      the compliance rate of a voluntary test at 4 months of age; 2) evaluation of the
      technical value of high-pressure liquid chromatography (HPLC) as a screening
      method; and 3) detailed biological characterization of all detected tumors.
      61,551 children were screened between May 1, 1990 and December 31, 1993.
      Participation was 69% in 1990, 81.5% in 1991, and over 83% in 1992. HPLC was a
      satisfactory assay method. The number of clinical examinations required for
      positive tests as defined in the protocol is 1 per 3,621 tests. The false
      positive rate is 1 per 3,583 tests. Eight neuroblastomas were discovered by
      screening (one stage I, three stage II, one stage III, three stage IVs). All are
      alive and well but were good prognosis cases according to the main prognostic
      factors. Five patients were discovered before screening (so called Halo effect):
      one stage I, one stage III, three stage IVs. One died of disease and four are
      alive in complete remission after treatment. Two patients were false negative
      (one stage III with N-myc amplification, one stage IV with bad prognosis
      features) and three cases of neuroblastoma were missed because of noncompliance
      with the screening program. This pilot study concludes on the feasibility of a
      mass screening program in France. The estimated cumulative incidence of
      neuroblastoma at 3 years is 1 per 4,375 living births and overdiagnosis is
      probable. All the detected cases were of good prognosis and the false negative
      ones were poor prognosis cases.

PMID- 8986144
TI  - Langerhans cell histiocytosis: an exploratory epidemiologic study of 177 cases.
AB  - There is little information available regarding epidemiologic risk factors for
      Langerhans cell histiocytosis (LCH). An exploratory investigation was conducted
      using information obtained from parents of 177 cases of LCH diagnosed before 21
      years of age (median 2 years). Utilizing data available from the Children's
      Cancer Group, LCH cases were compared to two matched control groups including 614
      patients diagnosed with a variety of childhood cancers and 318 community
      controls. Questionnaire data included information on demographics, prenatal and
      perinatal factors, complications in the neonatal period, environmental exposures,
      family medical history, and childhood exposures. Factors found to be
      statistically significantly associated with an increased risk of LCH included:
      maternal urinary tract infection during the index pregnancy, feeding problems
      during infancy, and blood transfusions during infancy. Use of supplemental
      vitamins was associated with a significantly decreased risk of LCH. Results from
      this exploratory study provide a basis for speculation on potential etiologic
      risk factors for LCH. Future epidemiologic investigations of LCH need to consider
      the presenting disease characteristics in assessing possible etiologic factors.

PMID- 8986146
TI  - Acute lymphoblastic leukemia in children: nonrandomized comparison of
      conventional vs. intensive chemotherapy at the National Cancer Institute of
      Colombia.
AB  - BACKGROUND: This study aimed to compare the therapeutic efficacy of two
      treatments for childhood acute lymphoblastic leukemia (ALL), and to evaluate the
      feasibility of intensive chemotherapy in a developing country. METHODS: The study
      was conducted at the National Cancer Institute in Bogota, Colombia. Untreated ALL
      patients under 16 years of age were divided into two groups: a historical control
      cohort (HC) of 141 patients treated with conventional chemotherapy and an
      intensive chemotherapy cohort (IC) of 130 patients treated with a modified Berlin
      Frankfurt-Munster protocol (m-BFM). Patients were clinically classified into risk
      categories for relapse, and followed through July 31, 1995. Disease-free survival
      (DFS) curves were obtained using the Kaplan-Meier method and were compared by the
      log rank test. RESULTS: Therapy groups had similar clinical baseline
      characteristics. Nonresponse rate to induction was higher in the HC group (16.3%)
      than in the IC cohort (7.6%) (P = 0.047), but deaths during induction were more
      frequent among m-BFM patients (13.8%) than in the HC group (6.4%) (P = 0.064).
      Bone marrow relapses after complete remission were less common in the IC group
      than in the HC group (19.4% and 45.9%, respectively; P = 0.0001), but central
      nervous system relapses showed no difference (12.8% in the HC and 16.3% under IC;
      P = 0.6). The DFS rates at 10 years were higher for the IC group, regardless of
      the baseline risk. CONCLUSIONS: IC reduces the frequency of relapses in ALL
      children in developing countries, when compared to previous therapy. A highly
      effective therapy such as m-BFM seems to be the most important predictor of
      outcome in children.

PMID- 8986145
TI  - Intermediate-dose methotrexate versus cranial irradiation in childhood acute
      lymphoblastic leukemia: a ten-year follow-up.
AB  - The cure rate of childhood acute lymphoblastic leukemia (ALL) has improved
      dramatically. Still there is a paucity of long-term data. With the improving cure
      rate, the quality of life and avoidance of second cancers have become important
      concerns. We evaluated 596 children and adolescents with ALL on Cancer and
      Leukemia Group B 7611 (CALGB 7611) who were randomized between 1976 and 1979 to
      receive intermediate-dose methotrexate (IDM) plus intrathecal methotrexate (IT
      MTX) or cranial radiation (CRT) plus IT MTX. After 10 additional years of follow
      up, the pattern and significance of the results reported in 1983 are confirmed.
      IDM offered better hematologic protection (P < 0.0006), better testicular
      protection (P = 0.002), but CRT offered better central nervous system (CNS)
      protection (P < 0.0001). The retrieval rate for the 231 patients who relapsed
      while on therapy or within 6 months of elective cessation of therapy is 20 +/-
      5%. For the 33 patients who relapsed more than 6 months after cessation of
      therapy, the retrieval rate is 49 +/- 10%. For all patients, the 12-year event
      free survival was 37 +/- 3.6% and the overall survival was 49 +/- 3.5%. There
      were two cases of second malignancies reported in 3,502 person-years of survival.
      Both occurred following salvage therapy. There was no evidence of an excessive
      number of second primaries over the general population of children. There were no
      reported instances of clinical cardiopathy. After a median follow-up of 11 years,
      there have been no reports of cardiopathy and no evidence of an increased risk of
      second cancers in children treated on CALGB 7611. While the overall outcome is
      not what would be expected with modern therapy, one can conclude that CRT offered
      better CNS protection, but IDM offered better systemic and testicular protection.
      A small risk of second cancers or cardiac dys-function may be acceptable with
      therapies which produce long-term documented survival benefits.

PMID- 8986147
TI  - Prognostic value of protein kinase C, proto-oncogene products and resistance
      related proteins in newly diagnosed childhood acute lymphoblastic leukemia.
AB  - In this investigation, untreated non-B-type acute lymphoblastic leukemia (ALL) of
      104 children was analyzed using immunocytochemistry for expression of protein
      kinase C, proto-oncogene products (Fos, Jun, Ras) and resistance-related proteins
      (topoisomerase II, P-glycoprotein, glutathione S-transferase-pi, metallothionein,
      dihydrofolate-reductase, thymidylate-synthase). The aim of the analysis was to
      find out whether combining those factors with the most important clinical
      prognostic factor (blast cell count) can improve the prognostic value (relapse
      free interval). Univariate analysis shows that protein kinase D (PKC), Fos, P
      glycoprotein (P-170) and glutathione S-transferase-pi (GST-pi) are significant
      prognostic factors independent of blast cell count (PBC) for the relapse-free
      intervals of children with ALL. The presence of the proteins Fos, PKC, P-170 and
      GST-pi was not independent within the patient population. The multivariate
      analysis showed that in combination with PBC and PKC, both P-170 and GST-pi have
      only limited prognostic influence. Combining the factors PKC, Fos and GST-pi as a
      categorical variable showed that this variable is a strong prognostic factor in
      addition to PBC.

PMID- 8986148
TI  - False positive images in the follow-up of patients with brain tumors.
AB  - In recent years, major advances in the diagnosis and treatment of patients with
      brain tumors have been seen. Today, evaluation of the central nervous system
      almost always includes magnetic resonance imaging (MRI). The appearance of a new
      lesion on the MRI scan of a patient previously treated for a central nervous
      system (CNS) tumor raises concern for recurrent disease with the need for
      selection of new, potentially toxic therapy. However, the sensitivity of MRI may
      allow demonstration of new lesions which are not due to tumor. We now report
      three patients with medulloblastoma who demonstrated new enhancing lesions on MRI
      following treatment of their tumors with surgery (3 patients), chemotherapy (2
      patients), and radiotherapy (2 patients). Two patients underwent resection of the
      lesion revealing gliosis. One patient had serial imaging that showed
      disappearance of the lesions. This suggests that not all new enhancing lesions in
      previously treated brain tumor patients represent tumor. Histologic proof of a
      suspicious lesion should be demonstrated prior to initiation of new therapy.

PMID- 8986149
TI  - Central nervous system involvement at diagnosis in a case of pediatric CD30+
      anaplastic large cell lymphoma.
AB  - Central nervous system (CNS) involvement in Ki-1/CD30 lymphoma is extremely rare,
      in contrast to the frequent involvement in other types of pediatric non-Hodgkin's
      lymphoma. No mechanism has yet been proposed to explain the sparing of the blood
      brain barrier in Ki-1/lymphoma. We present a 2-year-old boy who was admitted to
      the Department of Pediatric Hemato-Oncology due to lethargy, progressive
      breathing difficulties, massive diffuse lymphadenopathy, hepatosplenomegaly, and
      ichthyosis-like skin involvement with epidermolysis. A lymph node biopsy was
      compatible with Ki-1/CD30 anaplastic large cell lymphoma (ALCL). Bone marrow
      aspirate and biopsy demonstrated reactive hyperplasia. Cytogenetic analysis
      displayed hyperdiploid cells with 1p(-) in most cells. Cerebrospinal fluid
      examination showed pleocytosis with CD30+ cells. Possible mechanisms which could
      enable CNS involvement in this unusual case are discussed.

PMID- 8986150
TI  - A childhood fibrolamellar hepatocellular carcinoma with increased aromatase
      activity and a near triploid karyotype.
AB  - We report a 15-year-old boy with hepatocellular carcinoma (HCC) of the
      fibrolamellar type. He presented with advanced disease and a non-resectable
      tumor. Clinical features included marked gynecomastia which had been present for
      3 years, failure to enter puberty, and failure to thrive. These features might
      have been due to a high aromatase activity of the tumor. The course of the
      illness suggested that the tumor had been present for at least 3 years prior to
      diagnosis. At diagnosis the patient had multiple metastases which included
      infiltrated ascites. Cytogenetic analysis of the ascites revealed a near triploid
      karyotype with cell-to-cell variation and an abnormality of chromosome 1 q. This
      to our knowledge is the first karyotype report of fibrolamellar HCC in a child.

PMID- 8986152
TI  - Long-lasting complete remission after prolonged administration of etoposide in a
      child with a second recurrence of alveolar rhabdomyosarcoma.
AB  - The authors report a case of alveolar rhabdomyosarcoma (RMS) of the thigh
      complicated by two successive distant relapses shortly after radio- and
      chemotherapy, treated with etoposide, and resulting in complete long-lasting
      remission. The schedule of etoposide was 100 mg/ m2/d intravenously for three
      days weekly for 3 weeks, with an interval of 1 week between courses. This was
      administered for 11 months. The child is alive without disease and off therapy 20
      months after completion of etoposide treatment. Preclinical studies and
      experience in adults have suggested that the cytotoxic effects of etoposide show
      a marked dependence on schedule. A divided dose regimen of single-agent etoposide
      has previously been shown to have activity in relapsed rhabdomyosarcoma, but the
      outcome or the duration of complete response has not yet been fully evaluated. In
      out poor-prognosis case, the prolonged administration of etoposide achieved a
      long-lasting complete response.

PMID- 8986151
TI  - Hepatic angiosarcoma in a child: successful therapy with surgery and adjuvant
      chemotherapy.
AB  - We report a 3-year and 11-month-old Caucasian female, who initially presented
      with an unresectable hepatic angiosarcoma. After three courses of chemotherapy
      with adriamycin/cisplatin, the tumor decreased in size considerably, allowing
      complete surgical resection. She also received postoperative chemotherapy with
      alternating cycles of ifosfamide/etoposide, cisplatinum/adriamycin, and
      vincristine/actinomycin D/cyclophosphamide for 18 months. She remains disease
      free for greater than 44 months from the initial diagnosis. Our experience
      suggests that total excision of the tumor, together with an aggressive
      chemotherapy regimen, can improve the disease-free survival for children with
      this highly malignant vascular tumor of the liver.

PMID- 8986153
TI  - Successful pregnancy after conditioning with cyclophosphamide and fractionated
      total body irradiation.
AB  - We report the case of a 24-year-old man who received high-dose cyclophosphamide
      (CY) 120 mg/kg over 2 days and twice daily fractionated total body irradiation
      (TBI) over 3 days(1,320 cGy) prior to allogeneic bone marrow transplantation.
      Seven and one-half years later he fathered a normal child who has developed
      normally so far.

PMID- 8986154
TI  - Massive intra-atrial Wilms' tumor: a treatment dilemma.

PMID- 8986155
TI  - Subdural hematoma.

PMID- 8986156
TI  - Postpartum bilateral subdural hematomas following spinal anesthesia: case report.
AB  - BACKGROUND: Intracranial subdural hematoma is an exceptionally rare complication
      of spinal anesthesia. We report a case of this infrequent event and consider the
      influence of cerebral atrophy as a predisposing factor. METHODS AND RESULTS: This
      18-year-old woman with severe headaches was admitted to the hospital 42 days
      after delivery. She had a history of normal pregnancy and uneventful labor and
      delivery. The epidural anesthesia was satisfactory. Computed tomography showed
      bilateral chronic subdural hematomas that were surgically removed. An early
      follow-up scan showed marked resolution of the hematomas and a small sized brain
      with large subarachnoid space. A late follow-up scan confirmed the diagnosis of
      brain atrophy. CONCLUSIONS: Persistence of headache and gradual progression
      despite treatment must be regarded as a sign of intracranial complication
      following spinal anesthesia. In this case, cerebral atrophy is considered to be a
      contributory factor for the development of subdural hematoma following dural
      puncture.

PMID- 8986157
TI  - Acute spontaneous subdural hematoma of arterial origin: a report of five cases.
AB  - Acute spontaneous subdural hematoma of arterial origin is very rare. We report
      five patients who presented with a history of sudden onset of severe headache and
      vomiting and who developed progressive neurologic deficits, three becoming
      comatose. The symptomatologic onset was indistinguishable from other
      cerebrovascular disorders; none of the patients had a history of head trauma. In
      all our patients, the source of bleeding was identified at operation as a
      cortical artery located near the Sylvian region. Comparable cases in the
      literature are reviewed and the etiologic possibilities are discussed.

PMID- 8986158
TI  - Spontaneous acute subdural hematoma precipitated by cocaine abuse: case report.
AB  - A novel complication of the illicit use of cocaine, a spontaneous acute subdural
      hematoma, is described. This case represents another addition to the growing
      literature on the negative effects of cocaine on the central nervous system.
      Photographic documentation of the lesion responsible for the hematoma is
      presented, along with a discussion of the possible pathophysiologic mechanism.

PMID- 8986159
TI  - Risk factors of intracranial pressure monitoring in children with fiberoptic
      devices: a critical review.
AB  - BACKGROUND: Intracranial pressure (ICP) monitoring has become standard in the
      management of severe head injuries. A variety of monitoring techniques and
      devices are available, each with advantages and disadvantages; however there have
      been few studies in the pediatric population. METHODS: To study the risk factors,
      efficacy, and complication rate of fiberoptic ICP monitoring we studied 98
      consecutive children with severe head injuries over a 2-year period. The average
      patient age was 9 years and most had an initial Childrens Coma Score (CCS) of 8
      or less. The monitoring devices were placed in frontal parenchyma of all children
      and no prophylactic antibiotics were used. All fiberoptic catheter tips were
      cultured upon removal. RESULTS: The average duration of ICP monitoring was 7
      days; the usual range was 3-15 days, with the exception of one patient who
      underwent monitoring for 40 days. No complications occurred during insertion of
      the ICP monitors. Catheter tip cultures were positive for Staphylococcus
      epidermidis in 7% of the children, but none developed clinical features of CNS
      infection. The hospital location of placement or duration of ICP monitoring did
      not affect the rate of catheter tips with positive cultures. There was a 13%
      mechanical failure rate of the fiberoptic device. CONCLUSIONS: We conclude that
      fiberoptic ICP monitoring is safe and effective; however, there is a relatively
      low mechanical failure rate. Infection in uncommon despite prolonged use and
      there is little risk of complications associated with placement of this monitor.

PMID- 8986160
TI  - A rare case of hamartoma in the lateral ventricle: case report.
AB  - BACKGROUND: Intraventricular manifestation of a hamartoma is an unusual clinical
      entity. CASE DESCRIPTION: A 12-year-old girl was admitted with complaints of
      dizziness and head heaviness. Computed tomography and T1-weighted magnetic
      resonance imaging (MRI) demonstrated an isodensity or isointensity mass lesion
      with cystic component in the right lateral ventricle, which showed relatively
      high signal intensity on T2-weighted MRI and lacked contrast enhancement.
      Histopathologic examination on the surgically removed specimens using glial
      fibrillary acidic protein, Kluver-Barrera, Bodian stainings, bromouridine
      labeling index, and MIB-1 immunohistochemical staining confirmed that the tumor
      had glial and neuronal components and low proliferative potentiality. CONCLUSION:
      This case is the first report of intraventricular hamartoma, although some
      reports on intracranial hamartoma located in areas other than the hypothalamus
      have been published. The radiologic findings, including relatively high signal
      intensity on T2-weighted MRI and absence of contrast enhancement, may be
      suggestive of the diagnosis of intraventricular hamartoma; however, the specific
      stainings for glial and neuronal cells and proliferative evaluation are essential
      to the precise diagnosis of hamartoma. Clinical manifestation of hamartoma in the
      ventricular system, though rare, should be kept in mind.

PMID- 8986161
TI  - Intracranial germinoma with Down's syndrome: a case report and review of the
      literature.
AB  - BACKGROUND: Down's syndrome's association with malignancies such as leukemia is
      well known, but its association with brain tumor appears to be rare. We reviewed
      such rare cases of Down's syndrome and intracranial germ-cell tumor. CASE REPORT:
      A 10-year-old boy with Down's syndrome and intracranial germinoma located in the
      left basal ganglia is reported. The patient presented with right hemiparesis and
      was treated with a combination of surgery, chemotherapy with cisplatin and
      etoposide, and irradiation. CONCLUSIONS: We speculate that the percentage of germ
      cell tumors is high among Down syndrome patients with brain tumors and that the
      most common site is the basal ganglia.

PMID- 8986163
TI  - Coagulation alterations in patients undergoing elective craniotomy.
AB  - BACKGROUND: Thromboembolism remains a major problem in patients scheduled for
      craniotomy. The present study examined parameters of coagulation and fibrinolysis
      in 15 patients undergoing elective craniotomy in the perioperative period.
      METHODS: Plasma concentrations of thrombin antithrombin III complex (TAT),
      prothrombin fragment 1 + 2 (F1 + 2), and d-dimer were measured before and after
      induction of anesthesia, 60 minutes and 180 minutes after the beginning of
      surgery, and on the first postoperative morning. RESULTS: TAT, a marker of
      activation of coagulation, increased significantly (p < 0.05) from the
      preoperative measurements to the data obtained 60 minutes after beginning the
      surgery, reaching a maximum of 180 minutes after the start of surgery. F1 + 2,
      also indicating activation, showed a similar concentration time course with an
      intraoperative maximum. D-dimer, a marker of fibrinolysis, tended to increase
      slightly beginning 180 minutes after surgery with a maximum on the morning after
      surgery. Statistical significance for F1 + 2 and d-dimer was not found.
      CONCLUSIONS: This study showed a transient activation of coagulation with an
      intraoperative maximum in patients undergoing craniotomy. This result could be
      due to a liberation of thromboplastin from brain tissue.

PMID- 8986162
TI  - What the neurosurgeon needs to know about the coagulation system.
AB  - Intracranial surgery is often complicated by thromboembolic events including the
      life-threatening pulmonary embolism. After head trauma and in patients with brain
      tumors disseminated intravascular coagulation (DIC) can occur, characterized by
      the triggering of the coagulation cascade and the depletion of coagulation
      factors which ultimately leads to bleeding. The identification of patients at
      high risk as well as the early diagnosis of hemostatic problems uses routine
      laboratory parameters such as partial thromboplastin time and prothrombin time
      reflecting the intrinsic and the extrinsic pathway of the coagulation
      respectively. Thrombin antithrombin III complexes (TAT) and prothrombin fragment
      1 + 2 (F1 + 2) are further indicators of an activation of the coagulation whereas
      fibrinogen degradation products (FDP) refer to the fibrinolytic system. The basic
      principles of coagulation and fibrinolysis are summarized as well as the changes
      of laboratory parameters accompanying DIC, hypercoagulability and
      hyperfibrinolysis.

PMID- 8986164
TI  - Reoperation for recurrent malignant gliomas: what are your indications?

PMID- 8986165
TI  - Dislocation of the pituitary gland by sphenocavernous meningiomas.
AB  - BACKGROUND: Dislocation of the pituitary gland from the sella turcia by tumor has
      only very rarely been described. To date, only two cases have appeared in the
      neurosurgical literature. METHODS: After intraoperative identification of
      pituitary dislocation in five patients with cavernous sinus meningiomas, a review
      of our most recent 20 patients with cavernous sinus meningiomas was performed. A
      subgroup of sphenocavernous meningiomas was identified, as were the associations
      between pituitary dislocation and the patient's endocrinologic status. RESULTS:
      Of 20 consecutive patients with cavernous sinus meningiomas, seven tumors could
      be subclassified as sphenocavernous meningiomas due to the significant amount of
      tumor extension into the sphenoid sinus. At the time of surgery, dislocation of
      the pituitary gland from the sella into the suprasellar cistern was observed in
      five of seven of these patients. Four of the five patients with pituitary
      dislocation had evidence of hypopituitarism, whereas there was no evidence of
      this condition in the two patients with sphenocavernous meningiomas without
      pituitary dislocation. CONCLUSIONS: Pituitary dislocation in these patients is
      likely due to the physical dislocation of the pituitary gland from the sella,
      through an incompetent diaphragma sella, and by the tumorous extension in the
      sphenoid sinus. The extension of a cavernous sinus meningioma into the sphenoid
      sinus, and specifically the sella turcica, may be via the intercavernous venous
      sinuses. The lack of endocrinologic improvement suggests that the hypopituitarism
      noted in these patients is likely due to disturbance of the pituitary
      microcirculation with subsequent pituitary ischemia. The possibility of pituitary
      dislocation in patients with sphenocavernous meningiomas, especially those with
      panhypopituitarism, should be considered and searched for at the time of surgery.

PMID- 8986166
TI  - What are the actual incidence and mortality rates of subarachnoid hemorrhage?
AB  - BACKGROUND: From 1987-92 in Izumo City, Japan, we diagnosed 123 patients as
      having subarachnoid hemorrhage (SAH) by computed tomography, autopsy, or surgery
      (proven SAH); the crude incidence rate was 25/100,000/year for all ages. However,
      to estimate the actual incidence and mortality rates, we should take into account
      the decedents who died without confirmation by these methods but were presumed to
      have died of SAH. METHODS: From 1987-92, we reviewed all of 3562 death
      certificates for the city of Izumo (population 82,679), and calculated the
      incidence and mortality rates of SAH by combining proven and possible SAH.
      RESULTS: We diagnosed 36 patients as having possible SAH on death certificates.
      When adding these 36 patients to the 123 with proven SAH, the crude and the age
      adjusted and sex-adjusted incidence rates for all ages became 32/ 100,000/year
      and 29/100,000/year, respectively. Of these, 40% (64) died by day 3 (day 0
      defined as the day of hemorrhage), 43% (69) within 1 week, and 53% (84) within 1
      6 months, respectively. CONCLUSIONS: When including the patients who may have
      died of SAH, the actual incidence rate of SAH is much higher than that which has
      been reported to date, and the actual mortality rate is still very high.

PMID- 8986167
TI  - Therapeutic management of grade IV aneurysm patients.
AB  - BACKGROUND: The timing of surgery in patients suffering from subarachnoid
      hemorrhage grade IV and V according to Hunt and Hess, is still controversial.
      Several authors advocate early surgery for patients in poor clinical condition.
      Improved outcome and decreased mortality rates were reported. Others exclude
      patients in poor condition from early aneurysm surgery. METHODS: Forty grade IV
      aneurysm patients were admitted to our department. After ventriculostomy and
      cerebral angiography, 28 of them were operated on within 72 hours. The
      postoperative treatment included hypertensive, hypervolemic, hemodilutional
      therapy (triple-H therapy) and intensive monitoring (intracerebral pressure,
      blood pressure, hemodynamic parameters). The mean follow-up time was 6 months.
      RESULTS: Out of the 28 patients who underwent early surgery, 64% were in good
      health, 11% in poor health, 25% died; there were no survivors in a vegetative
      state. Twelve patients were treated conservatively; 50% died from infarction and
      rebleeding, before the operation was performed. Six underwent delayed aneurysm
      surgery after clinical improvement. In this group, 25% had good clinical outcome.
      CONCLUSIONS: Our results favor an aggressive treatment of grade IV aneurysm
      patients by means of ventricular drainage, early surgery and triple-H therapy.

PMID- 8986168
TI  - Delayed adjuvant therapy with the 21-aminosteroid U74006F and the anion channel
      blocker L644-711 does not improve outcome following thrombolytic therapy in a
      rabbit model of thromboembolic stroke.
AB  - BACKGROUND: Both the 21-aminosteroid U74006F, a potent inhibitor of lipid
      peroxidation, and L644-711, an anion channel blocker that inhibits both
      neutrophil and astrocyte function, have been previously shown to reduce brain
      injury in pretreatment paradigms of cerebral ischemia. It was therefore of
      interest to examine the effect of these agents in combination, when given on a
      delayed basis as adjuvants to thrombolytic therapy in a rabbit model of
      thromboembolic stroke. METHODS: Animals were mechanically ventilated and arterial
      blood gases controlled. Core and brain temperature, intracranial pressure, and
      mean arterial pressure were continuously monitored. Regional cerebral blood flow
      and hematocrit were measured hourly. Blood samples were taken to measure
      neutrophil (aggregation and chemiluminescence) and platelet (aggregation)
      activity. Following delivery of an autologous clot via the carotid artery, all
      experiments were continued for an 8-hour period. U74006F (3 mg/kg I.V.) and
      L644,711 (12 mg/kg I.V.) or their vehicle control (n = 8, each group) were given
      3.5 hours following autologous clot embolization. Both groups received tissue
      type plasminogen activator (t-PA) (6.3 mg/kg I.V.), beginning 4 hours following
      thromboembolic stroke and continuing over a 2-hour infusion period. Infarct size
      was determined following staining and image analysis. RESULTS: In the
      L644,711/U74006F group, neutrophil chemiluminescence was reduced following drug
      therapy; however, there were no significant differences between groups regarding
      infarct size (50.3 +/- 8.7 vs. 49.9 +/- 10.6, treatment vs. t-PA control, mean +/
      SEM), or in regional cerebral blood flow or intracranial pressure over time.
      CONCLUSIONS: It is concluded that prolonged (3.5 hours) delay of the initiation
      of therapy with the anion channel blocker L644,711 and the 21-aminosteroid
      U74006F fails to further reduce brain injury when given in combination with
      tissue plasminogen activator in a rabbit model of thromboembolic stroke.

PMID- 8986169
TI  - Postmyelographic computerized tomographic scan in the differential diagnosis of
      radiculomeningeal arteriovenous malformation: technical note.
AB  - BACKGROUND: The differential diagnosis of radiculomeningeal arteriovenous
      malformation (AVM) includes spinal intramedullary tumor and spinal cord myelitis.
      In making the diagnosis of radiculomeningeal AVM, clinical features of the
      history and magnetic resonance (MR) imaging findings are important initially,
      followed by selective spinal arteriography with or without myelography to confirm
      the diagnosis. The differential diagnosis, however, is not always easy. METHODS:
      We encountered five radiculomeningeal AVM and 14 intramedullary thoracolumbar
      tumors that were accurately diagnosed preoperatively. We performed
      postmyelographic computerized tomography (CT) in all five patients with
      radiculomeningeal AVM and five patients with intramedullary thoracolumbar tumors
      that were not able to exclude radiculomeningeal AVM with only MR imaging.
      RESULTS: In all our patients with radiculomeningeal AVM, postmyelographic CT
      demonstrated the dilated coronal venous plexus on the dorsal aspect of the spinal
      cord in contrast with a single swelling of the spinal cord in the patients with
      intramedullary tumor. CONCLUSIONS: We believe that this finding is useful when
      the serpentine dilated coronal venous plexus is not clearly identified on
      myelogram and selective spinal arteriography is not apparently indicated.

PMID- 8986171
TI  - Retroclival hematoma secondary to pituitary apoplexy.

PMID- 8986170
TI  - Surgical treatment of intractable seizures with multilobar or bihemispheric
      seizure foci (MLBHSF).
AB  - BACKGROUND: Patients with multilobar or bihemispheric seizure foci (MLBHSF) are
      generally not considered candidates for major resective surgery because of the
      high risk of complications. A combination of relatively less invasive surgical
      procedures were used to treat 19 patients with intractable seizures with MLBHSF.
      METHODS: Epileptogenic areas were identified via standard techniques. Locations
      of the seizure foci were in two lobes of a hemisphere in 11 patients, three lobes
      of a hemisphere in four patients, four lobes of a hemisphere in one patient, and
      both hemispheres in three patients. All 19 patients had multiple subpial
      transections; in addition, seven patients had small topectomies and nine patients
      had amygdala hippocampotomies. RESULTS: The longest follow-up is 54 months and
      the median for follow-up is 33 months. Nine patients (47%) are either free of
      seizures or have only rare seizures; eight patients (41%) have greater than 90%
      reduction in seizure frequency; one patient (6%) has complete cessation of
      myoclonic seizures and secondary generalization, and greater than 50% reduction
      in partial complex seizures; and one patient (6%) has greater than 50% reduction
      in seizure frequency. There were no permanent operative complications.
      CONCLUSION: Though the follow-up is relatively short and the number of patients
      is small, these results are encouraging, because the majority of patients in this
      group were poor surgical candidates.

PMID- 8986172
TI  - Language dominance in the cerebral hemispheres.

PMID- 8986173
TI  - Alzheimer's disease.

PMID- 8986174
TI  - Preparing and organizing for a lecture.
AB  - In a lecture, developing a strong organization assures strong delivery and a
      clear message. In this article preparation steps that will support the lecture
      are identified and described. These steps include: understanding the background
      and needs of the audience, establishing a clear purpose for the presentation, and
      being cognizant of the program planner's expectations of you. To assure a
      flawless lecture, several organizational imperatives are recommended.

PMID- 8986175
TI  - A competitive strategy for neurosurgery--Part I.

PMID- 8986176
TI  - The world 25 years from now: where will neurosurgery be?

PMID- 8986177
TI  - Not another database paper?

PMID- 8986178
TI  - Reflex sympathetic dystrophy treated with guanethidine. Time for a change of name
      and strategy.

PMID- 8986179
TI  - Data recording of problems during anaesthesia: presentation of a well-functioning
      and simple system.
AB  - BACKGROUND: As quality assurance, risk analysis and documentation become more
      important, rapid access to accurate information of departmental activity is
      needed. In this paper we describe a system for routine data recording of
      anaesthesia-related information, and we give examples of how this information can
      be used. METHODS: For each anaesthesia procedure we record 20 variables in a
      database. The variables are related to the patient, the procedure, and the
      anaesthesia. Both the type and severity of intraoperative problems are recorded.
      All information is routinely written on the standard anaesthetic chart, and later
      entered into a database. All charts are quality checked before data entry.
      RESULTS: With small modifications, we have used this system for 10 years, and it
      is well integrated as part of our departmental routine. From 1985 to 1995 we have
      recorded an increased incidence of 'minor' intraoperative problems, while the
      increase in 'severe' problems has been small. During the period 1993-95 the total
      problem incidence has been stable at around 14%. We have found the incidence of
      problems related to technical equipment to be 0.14%, and of 'minor' severity, and
      therefore equipment failure has not warranted extensive quality assurance
      efforts. We also investigated the impact of our routines for gastric emptying of
      non-fasting patients, and found an incidence of pulmonary aspiration of 0.03%.
      Our results made us conclude that our recommendations concerning anaesthetic
      technique and gastric emptying are safe. The system has proven to be simple
      enough to be practicable, and yet detailed enough to be informative for
      educational, quality assurance, research and administrative purposes. CONCLUSION:
      A simple database for information related to anaesthetic care and problems can be
      a useful tool for anaesthesiology departments. We have used the system for a
      variety of quality assurance efforts, for educational and administrative purposes
      and in research. To get reliable data it is important to keep the system simple,
      with the information recorded kept to a minimum. The software chosen must make it
      possible for people within the department to write and modify reports. A constant
      focus on data quality is important, and motivated nurses and doctors as well as
      leadership enthusiasm are necessary to make the system work properly. The
      atmosphere of problem recording should be one of 'openness and confidence',
      rather than 'inspection and control'.

PMID- 8986180
TI  - Routine preoperative gastric emptying is seldom indicated. A study of 85,594
      anaesthetics with special focus on aspiration pneumonia.
AB  - BACKGROUND: The aim of this study was to determine the incidence and severity of
      pulmonary aspiration of gastric contents during anaesthesia, to determine the
      short- and long-term morbidity, and to evaluate present routines for preoperative
      gastric emptying. During the study period, preoperative gastric emptying was done
      only when intestinal obstruction was suspected. METHODS: We routinely record
      prospectively all problems during and after anaesthesia by means of a database.
      All data for the 5 years from 1989 to 1993, a total of 85594 anaesthetic
      procedures, were analyzed. The hospital charts were also reviewed for those
      patients where aspiration to the lungs had occurred. RESULTS: Pulmonary
      aspiration of gastric contents was detected in 25 cases; all occurred in patients
      receiving general anaesthesia. The incidence was 4.1 times higher in emergency
      procedures than in electives. There were no aspirations in 30199 patients
      receiving regional anaesthesia. The complication occurred in all phases of
      anaesthesia, but clinical morbidity was low in most cases. Three cases showed
      serious morbidity immediately after the event, but recovered. Two cases showed
      serious long-term morbidity, but also recovered completely. No patients died. No
      cases, except possibly one, might have been prevented by stricter routines for
      preoperative gastric emptying. CONCLUSION: We found a low incidence of pulmonary
      aspiration. When it occurs, it carries a low risk for serious morbidity.
      Emergency cases for general anaesthesia are most at risk. Regional anaesthesia is
      considered safe. There is no evidence that preoperative gastric emptying should
      be routinely done in emergency cases, except in patients with suspected ileus/
      subileus.

PMID- 8986181
TI  - Infectious risks associated with the use of propofol.
AB  - BACKGROUND: Investigations of the Centers for Disease Control into postoperative
      infections have implicated extrinsically contaminated propofol. METHODS: To
      evaluate the infectious risk associated with intravenous anaesthetic agents, we
      surveyed the literature from 1971 to 1995 using the Medline database. Papers
      covering infections related to intravenous anaesthetic agents were included.
      RESULTS: The review of the literature on infections associated with propofol and
      other intravenous anaesthetics shows that this infectious risk is minimal and
      often caused by breakdowns in aseptic techniques. CONCLUSIONS: We conclude that,
      if standard hygienic precautions are taken, the risk of in-use contamination of
      intravenous anaesthetics is low. If strict hygienic guidelines are followed in
      handling propofol, this agent can be safely administered to patients.

PMID- 8986182
TI  - The use of countercurrent heat exchangers diminishes accidental hypothermia
      during abdominal aortic aneurysm surgery.
AB  - BACKGROUND: Perioperative hypothermia is common and likely contributes to
      morbidity, but the efficacy of prophylactic fluid warning has hardly been
      analyzed systematically. We tested the hypothesis that the use of an
      infusion/blood warmer, based on the principle of countercurrent heat exchange,
      reduces incidence and degree of severe hypothermia following aortic surgery.
      METHODS: In a prospective randomized investigation of patients (n = 50)
      undergoing elective abdominal aortic aneurysm surgery, all fluids/blood products
      (approx. 3500 ml) administered intraoperatively were infused either (n = 25) via
      countercurrent-like heat exchangers (Hotline Level 1 Technologies Inc.) or
      without (n = 25) taking special precautions (infusions stored at 21 degrees C,
      blood products heated to 37 degrees C in a water bath). Anaesthesia was
      standardized using a thiopentone, fentanyl, vecuronium induction sequence, and
      maintained by isoflurane in N2O/O2. RESULTS: The perioperative decrease of
      oesophageal temperature (-0.35 degree C +/- 0.4) in the group managed with heat
      exchangers was significantly smaller (P < 0.0001) than in the control group (-1.5
      degrees C +/- 0.54), and oesophageal temperature at the end of surgery was
      considerably higher (35.1 degrees C +/- 0.45 vs. 34.2 degrees C +/- 0.7; P <
      0.0001). Furthermore, while postoperative hypothermia below 34.5 degrees C was
      observed in 16 patients (incidence: 64%) of the control group, it occurred in
      only 2 patients (incidence: 8%) managed with heat exchangers (P < 0.001).
      CONCLUSIONS: The efficacy of fluid/blood warmers has hitherto only been evaluated
      in bench tests. Our results demonstrate that the use of heat exchangers alone,
      while not completely preventing hypothermia, markedly reduces the incidence of
      severe perioperative hypothermia, and lessens its degree during abdominal aortic
      aneurysm surgery.

PMID- 8986183
TI  - Pre-eclampsia: the effect of intravenous fluid preload on atrial natriuretic
      peptide secretion during caesarean section under spinal anaesthesia.
AB  - BACKGROUND: The haemodynamic effect of volume load at elective Caesarean delivery
      may be modulated by atrial natriuretic peptide (ANP) especially in pre-eclamptic
      women in whom basal ANP levels are increased. METHODS: We followed the
      haemodynamic parameters and determined the peripheral venous levels of ANP before
      and after an intravenous volume preload of 1000 ml of Ringer's acetate solution,
      followed by a further load of the same volume under spinal anaesthesia in 7
      healthy and in 6 pre-eclamptic women. RESULTS: During the preload period the
      median ANP level increased more (from 14.8 to 22.1 pmol/l, P = 0.03) in pre
      eclamptic than in healthy women (from 8.0 to 8.5 pmol/l, NS); while an increment
      in central venous pressure (CVP) was also greater in pre-eclamptic than in
      healthy women. The increase in the concentrations of ANP correlated significantly
      (P < 0.05) with the increase in CVP in the total study group. A significant
      increase in ANP levels in healthy pregnant women was not seen until during the
      second infusion period under spinal anaesthesia; in pre-eclamptic women the
      levels increased further during that period. CONCLUSION: These findings concur
      with the theory that atrial stretch is a stimulus for ANP release. An exaggerated
      release of ANP in response to volume loading may aid in the adaptation of
      maternal circulation to volume load at elective Caesarean delivery in pre
      eclamptic women.

PMID- 8986184
TI  - Effect of pre- vs postoperative tonsillar infiltration with local anesthetics on
      postoperative pain after tonsillectomy.
AB  - BACKGROUND: Since pre-incisional peritonsillar infiltrations of local anesthetic
      solutions have been suggested to reduce postoperative pain after tonsillectomy,
      we compared the efficacy of either pre- or postoperative local anesthetic
      infiltration upon post-tonsillectomy pain. METHODS: After the induction of
      general anesthesia, 68 consecutive healthy patients, ranging in age from 8 to 65
      years, were randomly allocated to either receive peritonsillar infiltration with
      0.25% bupivacaine (group 1) or normal saline (group 2) before incision. A third
      group (group 3) had their peritonsillar region infiltrated with 0.25% bupivacaine
      after the completion of surgery but before the patients were awakened from
      anesthesia. All the patients were treated in the same way in the postoperative
      period: NSAIDs were given intravenously to adults and rectally to children.
      Acetaminophen was given intravenously or rectally (children aged < 15 yr) if
      additional analgesic support was requested by the patient. Additional
      acetaminophen consumption was recorded daily. Pain scores were assessed on every
      patient with the use of a visual analogue scale (VAS) at rest, 1, 5, 9, 13, 17,
      21 and 36 h after surgery, and also on swallowing during the first postoperative
      day. RESULTS: Global VAS pain scores were lower in the groups treated with
      bupivacaine infiltration during the first 24 h after surgery (P < 0.05).
      Supplementary analgesic consumption was lower in group 3 than in group 2 during
      the 0-9 h interval immediately following surgery (P < 0.05). There were no
      statistically significant differences for any other parameters between the 3
      groups. CONCLUSION: These results suggest that the timing of peritonsillar
      infiltration with bupivacaine is not of clinical importance and does not affect
      the quality of postoperative analgesia in patients undergoing tonsillectomy.

PMID- 8986185
TI  - Intravenous guanethidine in patients with reflex sympathetic dystrophy.
AB  - BACKGROUND: Intravenous regional guanethidine Bier block (IVRGBB) has been used
      predominantly in Europe for treating reflex sympathetic dystrophy (RSD). Our
      experience in the United States, where its use has been limited, is reported.
      METHODS: Fifty-five patients received IVRGBB for RSD. Upper extremities received
      20 mg (10 mg/ml) of guanethidine in 30-50 ml of 0.5% lidocaine; lower extremities
      received 40 mg in 40-75 ml of lidocaine (volume adjusted for size, weight, or
      prior adverse effect). Pain severity (mild, moderate, severe, excruciating) was
      obtained pretreatment. Pain severity and a global clinical assessment (GCA)
      (resolved, improved, no change, worse) were obtained following each treatment.
      The final GCA was analyzed vs: pretreatment score; age; sex; pain duration;
      number of treatments; and precipitating event. Adverse effects were documented.
      RESULTS: Of 55 enrolled patients, 2 were lost to follow-up, and 2 returned 1 and
      4 years later for repeat treatment. Therefore, 53 patients were evaluated for 55
      treatments. Age: 38.2 +/- 14.8 (SD) (range 10-77) years. Sex: 11 males, 44
      females. Average pain duration: 2.0 +/- 1.7 years (3 days-7 years). Final
      assessment occurred at 3.88 +/- 5.21 months (6 days-22/3 years). Effect on pain:
      resolution-9.1%; improved-14.5%; no change-61.8%; worsening-14.5%. No significant
      relationship was found between GCA and the factors evaluated. There was a
      significant positive linear association between pretreatment pain and post
      treatment GCA (P = 0.032). Fifty-six adverse effects occurred in 19 (34.5%)
      patients (nausea, vomiting, orthostatic hypotension, dizziness, diarrhea,
      weakness). CONCLUSIONS: IVRGBB does not provide long-term pain relief and is
      associated with adverse effects in over 1/3 of patients.

PMID- 8986186
TI  - Intra-articular tenoxicam relieves post-arthroscopy pain.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs have been documented to be
      effective in the treatment of postoperative pain. The aim of this study was to
      evaluate the analgesic effect of local intra-articular injection of tenoxicam
      compared with intravenous injection on postoperative pain after arthroscopy.
      METHODS: After day-case arthroscopy, 60 patients were randomized to receive
      either tenoxicam 20 mg in 20 ml of normal saline intra-articularly and 2 ml of
      normal saline i.v., or 20 ml of normal saline intra-articularly and 2 ml
      tenoxicam 20 mg i.v. Postoperative pain was assessed using a visual analogue
      scale and measuring analgesic requirements. RESULTS: Pain scores were
      significantly lower in the intra-articular group at rest and during active
      flexion of the knee at 1, 2 and 4 hours postoperatively and during walking at 6
      hours postoperatively (P < 0.05). Significantly more patients in the intravenous
      group required supplemental opioid analgesia within the first 4 hours
      postoperatively (P < 0.05). CONCLUSION: Intra-articular tenoxicam 20 mg provided
      better analgesia and decreased the requirements for postoperative analgesic
      compared with i.v. tenoxicam 20 mg.

PMID- 8986188
TI  - Tourniquet release: systemic and metabolic effects.
AB  - The pneumatic tourniquet produces ischemic changes in limbs. The effects of
      tourniquet release on systemic blood pressure and metabolic parameters were
      studied in 11 adult patients undergoing total knee replacement under general
      anesthesia. Mean arterial pressure (MAP) decreased rapidly after the release of
      the tourniquet, becoming significant at 3 min and remaining significantly
      depressed up to 15 min post release. Arterial pH, PaO2, PaCO2, lactate acid, and
      potassium changed significantly after the release, but normalized within 30 min.
      These results are notably different from a previous study in a similar patient
      population undergoing knee replacement under epidural anesthesia. Compared to
      patients under epidural anesthesia, patients receiving general anesthesia with
      mechanical ventilation are unable to compensate for the metabolic load caused by
      the tourniquet release, as the latter group are unable to alter their ventilatory
      rate. In elderly patients with decreased cardio-pulmonary reserve, this may be of
      clinical importance.

PMID- 8986187
TI  - Fluid therapy with Ringer's solution versus Haemaccel following coronary artery
      bypass surgery.
AB  - BACKGROUND: Crystalloid and colloid infusion can be used in volume therapy
      following heart surgery. In this prospective, randomised study we compared
      Ringer's solution (group R) to Haemaccel (group H) following coronary artery
      bypass grafting. METHODS: A stringent protocol for adjusting the infusion rate
      was used. Haemodynamic parameters and pulmonary function were evaluated as well
      as chest tube drainage. The double-indicator dilution method was used to measure
      total blood volume index (TBVI), intrathoracic blood volume index (ITB-VI) and
      extravascular lung water index (EVLWI). RESULTS: Haemodynamic stability was
      achieved in both groups throughout the study period, as judged from mean arterial
      pressure, central venous pressure, pulmonary capillary wedge pressure, and
      cardiac index. However, the total volume infused was significantly higher in
      group R. TBVI and ITBV were higher in group H, although only significant at 8 h
      for TBVI. Pulmonary function was similar in both groups. There was no significant
      difference in EVLWI, pulmonary shunt fraction, and time on mechanical
      ventilation. Likewise, chest tube drainage was not significantly different in
      both groups. CONCLUSION: We conclude that volume therapy with Haemaccel following
      heart surgery requires less volume and achieves better filling of the circulation
      compared to Ringer's solution.

PMID- 8986189
TI  - Continuous end-tidal carbon dioxide monitoring during normofrequent jet
      ventilation.
AB  - BACKGROUND: Continuous end-tidal carbon dioxide (ETCO2) monitoring during
      normofrequent jet-ventilation (NFJV) has not previously been successful and no
      correspondence between ETCO2 and arterial carbon dioxide (PaCO2) demonstrated.
      METHODS: During NFJV jet-ventilation in 19 healthy volunteers, continuous ETCO2
      was measured and compared to PaCO2 values. The original ETCO2 sampling line from
      our Datex CO2 measuring equipment was placed longitudinally against a suction
      catheter and both were wrapped with aluminium foil. They were placed 4-5 cm above
      the carina and the position was verified with a fiberoptic bronchoscope. RESULTS:
      The correlation between methods gave a Pearson's product moment correlation (r
      value) of 0.836, significant at the P < 0.001 level, indicating a close
      correlation between methods. A difference against mean scatter diagram confirmed
      that ETCO2 and PaCO2 measurements are of equal value in monitoring healthy
      patients during NFJV. CONCLUSION: A valuable method of continuous ETCO2
      monitoring during NFJV is presented.

PMID- 8986190
TI  - Effects of halothane, isoflurane and sevoflurane on ischemia-reperfusion injury
      in the perfused liver of fasted rats.
AB  - BACKGROUND: Although intraoperative ischemia-reperfusion of the liver generally
      occurs under general anesthesia, little is known about the direct effect of
      anesthetic agents on hepatic injury due to this phenomenon. The effect of
      volatile anesthetics on ischemia-reperfusion injury was studied using isolated
      liver perfusion. METHODS: The liver was isolated from 24-h-fasted male Sprague
      Dawley rats and perfused through the portal vein with a modified Krebs-Ringer
      bicarbonate solution in a recirculating perfusion-aeration system. Ischemia was
      induced by reducing the baseline perfusion pressure from 1.2 to 0.2 kPa followed
      by reperfusion to baseline level. The ischemia-reperfusion injury was assessed by
      LDH release from the perfused liver. We studied the effect of halothane,
      isoflurane and sevoflurane on the ischemia-reperfusion injury during 20 min of
      control conditions, exposure of the liver to 60 min of ischemia and reperfusion
      for 90 min. RESULTS: Ischemia was evident by reduced portal vein flow and oxygen
      consumption, and caused an increase in lactate production. Reperfusion caused a
      transient reduction in lactate production and a significant increase in LDH
      release. All anesthetics reduced hepatic oxygen consumption and increased the net
      lactate production during control conditions. Volatile anesthetics also
      significantly attenuated LDH release during reperfusion. The suppression of LDH
      release was observed even when isoflurane was administered during the reperfusion
      period, but not when it was administered only during ischemia. CONCLUSION: These
      results indicate that volatile anesthetics may protect the fasted liver from
      early, neutrophil-independent, ischemia-reperfusion injury by acting during the
      reperfusion phase.

PMID- 8986191
TI  - Intracranial subdural haematoma--a rare complication following spinal
      anaesthesia.
AB  - We present a rare case with postspinal headache resulting in an intracranial
      subdural haematoma. After 5 days of persistant headache the condition was
      recognized and diagnosed on a computerized tomography-scan (CT) of the skull. The
      patient was operated with evacuation of the haematoma 2 weeks after the spinal
      anaesthesia and recovered completely.

PMID- 8986193
TI  - A simple method of ventilation via the laryngeal mask during transportation and
      recovery from anaesthesia.

PMID- 8986192
TI  - Dihydroergotamine in the treatment of head injury--risk of gangrene and renal
      failure.

PMID- 8986194
TI  - Effect of administered ethanol on protein kinase C in human platelets.
AB  - There are numerous reports of the effect of ethanol on protein kinase C (PKC) in
      animals or with in vitro systems. However, the effect of ethanol on PKC in humans
      has not been extensively investigated despite the large number of studies
      involving PKC and human platelets. In this study, we administered ethanol to
      human volunteers and determined the level of PKC before and after a 0.4 g/kg dose
      of ethanol. We studied Native Americans and Caucasians of both sexes. There was
      an increases in PKC activity 60 min after ethanol administration. There were no
      ethnic, age, nor gender differences detected, nor was there any correlation
      between family history of alcoholism and the basal or stimulated platelet PKC
      levels. Neither was there any correlation of basal or stimulated PKC activity
      with the genotypes for ADH2, ADH3, ALDH2, CYP2E1, and CYP1A2.

PMID- 8986195
TI  - Alcohol consumption, gamma-glutamyl transpeptidase (GGT), and pulmonary function:
      a cross-sectional and longitudinal study in working men.
AB  - Epidemiological studies of the relationships between pulmonary function and
      reported alcohol intake showed inconsistent results. The use of biological
      markers of alcohol is needed. The objective of this study was to assess the
      relationships of alcohol consumption, assessed by a standardized questionnaire,
      and gamma-glutamyl transpeptidase (GGT), to forced expiratory volume in 1 sec
      (FEV1) level and decline over 10 years, in working men. Three hundred twenty
      eight policemen aged 22-55 years were examined in 1980 (first survey) and again
      in 1990 (second survey). The two cross-sectional analyses used the 1980 data and
      the 1990 data separately. Longitudinal analysis used 1980 alcohol consumption and
      GGT values, and 10-year FEV1 decline. In both cross-sectional surveys, elevated
      alcohol consumption was significantly associated with impaired age-adjusted and
      height-adjusted FEV1. Further adjustment for smoking habit, education level, and
      asthmatic status did not alter these results. An increase of 25 g/day of alcohol
      was associated with 50.0 ml (95% confidence interval: 1.5 to 98.5) and 55.3 ml
      (95% confidence interval: 7.8 to 102.8) decrease of corresponding multivariate
      adjusted FEV1 in 1980 and in 1990, respectively. GGT was also negatively
      associated with FEV1 in both cross-sectional surveys. Similar patterns of
      associations were also observed between vital capacity measurements and alcohol
      variables. In the longitudinal analysis, there was no relationship between either
      alcohol consumption or GGT and FEV1 decline. Findings suggest that alcohol
      consumption was associated with impaired lung function, but there was no evidence
      of accelerated FEV1 decline over 10 years related to alcohol consumption in this
      "healthy" population of middle-aged men.

PMID- 8986196
TI  - Serum markers for hepatic fibrosis in alcoholic liver disease: which is the best
      marker, type III procollagen, type IV collagen, laminin, tissue inhibitor of
      metalloproteinase, or prolyl hydroxylase?
AB  - Although various serum markers for the evaluation of hepatic fibrosis have been
      introduced, it remains unclear which is the best marker to evaluate the hepatic
      fibrosis observed in alcoholic liver disease (ALD). In this study, we measured
      serum concentrations of the immunoreactive beta-subunit of prolyl hydroxylase,
      procollagen type III peptide, the 7S domain (7S-IV) and triple-helix domain (TH
      IV) of type IV collagen, laminin, and tissue inhibitor of metalloproteinase
      (TIMP) in patients with and without ALD (non-ALD), and controls to evaluate the
      best serum marker reflecting the characteristic histologic features of ALD. After
      Azan-Mallory and silver-impregnated reticulin staining, histologic specimens were
      examined; and the degree of hepatic fibrosis was classified as mild, moderate, or
      severe. Although serum concentrations of all markers, except for TIMP, in
      patients with each type and stage of liver disease were higher than cut-off
      values and these concentrations increases with the progression of liver disease,
      statistical analyses indicate that serum TH-IV concentration is the best marker
      to distinguish ALD from non-ALD. A good correlation was also found between the
      hepatic type IV collagen content and serum TH-IV, but not serum 7S-IV
      concentration. Moreover, after abstinence from alcohol, serum concentrations of
      TH-IV decreased more quickly than other serum markers. These results clearly
      suggest that, compared with other markers, serum concentration of TH-IV may more
      strongly reflect the histologic features of ALD. However, other serum markers,
      except for TIMP, may be useful in evaluating the degree of hepatic fibrosis.

PMID- 8986197
TI  - Alcohol, central nervous system injury, and time to death in fatal motor vehicle
      crashes.
AB  - OBJECTIVES: Motor vehicle crash (MVC) studies have found that alcohol (ALC) is
      associated with increased mortality and decreased time to death (TTD). Clinical
      and experimental data suggest that ALC potentiates central nervous system injury
      (CNSI). We hypothesize that ALC-intoxicated, MVC fatalities with CNSI are more
      likely to die in the immediate postinjury period than are sober victims with
      CNSI. Methods; DESIGN: A retrospective cohort of 401 MVC fatalities from four
      Michigan counties for the time period 1985 to 1991 was studied. MEASUREMENTS:
      Medical examiner records were reviewed to determine age, blood alcohol
      concentration (BAC), and TTD. Injury severity was calculated with the Abbreviated
      injury Scale (1985 version). Anatomical profile scores and G scores were also
      calculated and used to identify CNSI subjects. ANALYSIS: chi 2 and Student's t
      test were used, and odds ratios with 0.95 confidence intervals (CIs) were
      calculated. RESULTS: ALC(+) cases (BAC > or = 100 mg/dl) (n = 99) were
      significantly younger and more frequently had TTD < 1 hr than ALC(-) cases (n =
      233): odds ratio 1.62[0.95 CI (1.02 to 2.58)]. Overall, CNSI cases (n = 297) were
      significantly younger and had fewer thoracic injuries, but did not have
      significantly shorter TTD, compared with non-CNSI cases. However, ALC(+) CNSI
      cases (n = 77) were over twice as likely to have TTD < 1 hr ?odds ratio 2.04
      [0.95 CI (1.13 to 3.70)]?. For ALC(+) isolated CNSI cases, the odds ratio for TTD
      < 1 hr, compared with nonisolated CNSI cases was 8.25 (0.95; CI 0.66 to 102.5).
      Injury Severity Score, anatomical profile, and G scores were not significantly
      different for ALC(+) CNSI cases, compared with ALC(-) CNSI cases, whether
      isolated or nonisolated. CONCLUSIONS: These data suggest that alcohol
      intoxication is associated with increased frequency of early death in MVC victims
      with CNSI, despite there being no detectable difference in anatomical injury
      scoring.

PMID- 8986198
TI  - Alcohol effects on the heritability of EEG spectral power.
AB  - To estimate the effects of a moderate dose of alcohol on heritability of the EEG
      power spectrum, 53 monozygotic and 38 like-sexed dizygotic Caucasian twin pairs
      (aged 30.0 +/- 7.0 years) were studied. Subjects were asked not to drink alcohol
      for 2 days and to fast after midnight before a protocol of: (1) a low fat meal at
      8:00 AM; (2) a baseline EEG recording; (3) ingestion of alcohol over 10 min,
      which raised the breath alcohol concentration to 0.057 +/- 0.017% (SD); followed
      by (4) a postalcohol EEG recording 35.1 +/- 5.7 (SD) min after the start of
      drinking. One previous study (Propping, P., Hum. Genet. 35: 309-334, 1977) found
      that heritability (H2), the fraction of total variance in the EEG power that is
      attributable to genetic influences, increased after alcohol administration. In
      the current study, H2 of log-transformed, body-weight-adjusted spectral band
      power increased after alcohol for the theta-, alpha-slow, alpha-fast, beta-slow,
      and beta-fast bands (from an average of 0.47 to an average of 0.80). The increase
      in heritability was accompanied by a significant decrease in the within-pair
      differences of monozygotic cotwins for all of the same frequency bands except
      beta-fast. Because within-pair differences are expected to contain only
      environmental factors for the genetically identical individuals, it was concluded
      that alcohol decreases environmental variation of EEG power spectral density,
      causing the increase in H2.

PMID- 8986199
TI  - Genetic predisposition to organ-specific endpoints of alcoholism.
AB  - Medical records of the 15,924 twin-pairs in the National Academy of Sciences
      National Research Council (NAS-NRC) twin registry were collected for an
      additional 16 years through 1994 when the surviving twins were aged 67 to 77
      years. Compared with earlier analyses (Hrubec, Z, and Omenn, G. S., Alcohol.
      Clin. Exp. Res., 5:207-215, 1981), when subjects were aged 51 to 61, there were
      23% more diagnoses of alcoholism (34.4 per 1,000 prevalence), 32% more diagnoses
      of alcoholic psychosis (5.4 per 1,000), and 25% more twins with liver cirrhosis
      (17.7 per 1,000). Overall, 5.3% of the cohort had at least one of the diagnoses
      related to alcoholism. Probandwise concordance rates (%) were: alcoholism-26.7
      monozygotic (MZ), 12.2 dizygotic (DZ) (p < 0.0001); alcoholic psychosis-17.3 MZ,
      4.8 DZ (p < 0.05); and cirrhosis-16.9 MZ, 5.3 DZ (p < 0.001). Concordance for any
      diagnosis related to alcoholism was 30.2 MZ, 13.9 DZ (p < 0.0001). Maximum
      likelihood modeling indicated that approximately 50% of the overall variance was
      due to additive genetic effects; in all diagnosis categories, a totally
      environmental model gave a significantly poorer fit to the data. Bivariate and
      trivariate genetic analyses indicated most of the genetic liability for the organ
      specific endpoints of psychosis and cirrhosis was due to the shared genetic
      liability for alcoholism. Once the shared variance with alcoholism was
      considered, there was no further shared genetic liability for psychosis and
      cirrhosis. Our results confirm Hrubec and Omenn's conclusion that there was
      significantly greater concordance in MZ twins-pairs for alcoholic psychosis and
      cirrhosis in the NAS-NRC twins, and concordance rates remained similar to those
      reported 16 years earlier. In contrast, we found most of the genetic liability to
      organ-specific complications of alcoholism was shared with the genetic liability
      for alcoholism per se; only a small portion of the genetic variance of the
      individual complications was independent of the genetic predisposition for
      alcoholism.

PMID- 8986200
TI  - Fluoxetine treatment seems to reduce the beneficial effects of cognitive
      behavioral therapy in type B alcoholics.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that, because of
      abnormalities in serotonergic neurotransmission that may underlie craving and
      impulsive behavior, fluoxetine treatment differentially affects drinking among
      type B alcoholics, who are characterized by high levels of both premorbid
      vulnerability and alcohol-related problems. METHODS: Using a k-means clustering
      procedure, alcohol-dependent subjects from a placebo-controlled trial of
      fluoxetine were grouped into low-risk/severity (type A: n = 60) and high-risk/
      severity (type B: n = 35) groups. Multivariate analysis of covariance (with
      pretreatment measures as covariates) evaluated the effects of Alcoholic Subtype,
      Medication Group, Treatment Completion, and their interactions on measures of
      drinking, both during the 12-week treatment period and a 6-month follow-up
      period. RESULTS: Although there were no main effects of Alcoholic Subtype or
      Medication Group, subjects who completed the treatment trial showed significantly
      better drinking-related outcomes. There was also an interaction of Alcoholic
      Subtype by Medication Group during treatment. Among type B subjects, fluoxetine
      treatment resulted in poorer drinking-related outcomes than placebo treatment.
      Among type A subjects, there was no effect of Medication Group. This interactive
      effect did not persist during the 6-month follow-up period. CONCLUSIONS:
      Alcoholic subtypes identified by cluster analysis seem to be differentially
      responsive to the effects of fluoxetine treatment on drinking-related outcomes.
      Serotonergic abnormalities previously identified among a subgroup of alcoholics
      who are also characterized by impulsivity and severity of alcohol dependence may
      help to explain the differential medication effect. Based on these findings, it
      is recommended that, in the absence of a comorbid mood or anxiety disorder,
      fluoxetine not be used to maintain abstinence or reduce drinking in high
      risk/severity alcoholics.

PMID- 8986201
TI  - Ethanol-induced change in cardiac and endogenous opiate function and risk for
      alcoholism.
AB  - Susceptibility to alcoholism varies with age, gender, and familial background.
      Youthful nonalcoholic males with multigenerational family histories of male
      alcoholism seem at particular risk. Previous investigations suggest that such
      males are characterized by abnormal psychophysiological response, while sober and
      alcohol-intoxicated; additional recent studies indicate that the endogenous
      opiate systems are involved in mediating ethanol reinforcement and modulating
      intake. We first compared cardiac response to alcohol administration among young
      (mean = 22.8 years), nonalcoholic men and women with multigenerational,
      unigenerational, and negative family histories of alcohol dependence and abuse.
      Then, we compared the ethanol-induced cardiac response of the males in these
      three groups to that of currently alcohol-dependent older males and age-matched
      nonalcoholic male controls. Finally, we examined ethanol-induced change in plasma
      beta-endorphin and cortisol levels among a subset of the nonalcoholic males,
      divided into those with high and low levels of postethanol administration heart
      rate increase. Nonalcoholic males with multigenerational family histories of male
      alcoholism were characterized by significantly higher [t(301) = 5.70, p < 0.0001,
      Cohen's d = 0.73] levels of ethanol-induced heart-rate increase than
      nonalcoholics from all other comparison groups. The magnitude of their increase
      matched that of current male alcohol-dependents. Nonalcoholic males with high
      levels of ethanol-induced heart-rate increase also produced significantly more
      plasma beta-endorphin after consuming alcohol. Peak production of beta-endorphin
      was highly correlated (r = 0.861, p < 0.001) with magnitude of heart-rate
      increase. A subset of those at risk for alcoholism may be characterized by
      sensitivity to ethanol-induced reward, marked by heightened ethanol-induced,
      heart-rate increase, mediated by ethanol stimulation of endogenous opiate
      production. This subset might contain those who, once alcoholic, would
      differentially benefit from treatment with opiate antagonists.

PMID- 8986202
TI  - A comparative analysis of alcohol in fatal and nonfatal bicycling injuries.
AB  - Bicycling is the leading cause of recreational injury, resulting in more than
      half a million emergency department visits and about 900 deaths each year in the
      United States. Previous research on bicycling injury was conducted predominantly
      in children and focused on the effectiveness of safety helmets. Few studies have
      examined the role of alcohol in bicycling injuries. This study examined the
      magnitude of and factors related to alcohol involvement in fatal and nonfatal
      bicycling injuries, and tested the hypothesis that alcohol intoxication is
      associated with significantly increased likelihood of fatality given a serious
      bicycling injury. Medical examiner data on all fatally injured bicyclists aged 10
      years or older from 1987 to 1994 in Maryland (fatal cases, n = 63) were compared
      with trauma registry data on all injured bicyclists who were treated at a
      regional trauma center during the same time period (nonfatal cases, n = 253) on
      variables related to blood alcohol concentrations (BACs), demographic
      characteristics, and injury circumstances. The fatal cases were more likely than
      the nonfatal cases to have positive BACs (30% vs. 16%, p < 0.01) and to be
      legally intoxicated (i.e., BACs > or = 0.10%) (22% vs. 13%, p < 0.01). For both
      fatal and nonfatal cases, intoxication was more prevalent among victims who were
      male, aged 20 to 39 years, or who were injured at nighttime (7:00 PM to 6:59 AM).
      Bicyclists who died at the scene were four times as likely as those who died at
      hospitals to be legally intoxicated (35% vs. 9%, p < 0.02). Given a serious
      bicycling injury, intoxication was associated with significantly increased
      likelihood of fatality, with an adjusted odds ratio of 2.8 (95% confidence
      interval, 1.3 to 6.3). This increased likelihood of fatality was probably due in
      part to the fact that the rate of helmet use at the time of injury among the
      intoxicated was much lower than among the sober (6% vs. 31%, p < 0.05). Results
      indicate that alcohol plays an important role in fatal and serious bicycling
      injuries. Preventing intoxicated biking should be incorporated into helmet
      campaigns and other bicycle safety programs.

PMID- 8986203
TI  - Biological responses to administered interferon in alcoholics.
AB  - To elucidate the influence of chronic alcohol intake on interferon (IFN) therapy
      in patients with various diseases, 3 million units of natural IFN (nHuIFN-alpha
      Ly) was administered once to alcoholics, nonalcoholic chronic hepatitis C (CH-C)
      patients, and healthy subjects. The serial changes of serum activity of 2'-5'
      oligoadenylate synthetase, serum levels of beta 2-microglobulin, C-reactive
      protein (CRP), and body temperature were monitored. The increase in the activity
      of 2'-5' oligoadenylate synthetase, the response of serum-reactive protein, and
      body temperature after IFN administration were significantly lower in the
      alcoholics than those in CH-C group, and healthy subjects (control group). The
      serum beta 2-microglobulin level was already higher in the alcoholics before IFN
      administration than those of the control group and the CH-C group. These findings
      suggest that physiological responses to exogenous IFN in alcoholics are generally
      decreased. Hence, for the maximum effect of IFN therapy, it is important for
      patients to abstain from alcohol intake and for doctors to carefully consider the
      timing of initiation.

PMID- 8986204
TI  - Distribution of peripheral blood lymphoid subsets in alcoholic liver cirrhosis:
      influence of ethanol intake.
AB  - The aim of the present study was to investigate the effect of chronic ethanol
      (EtOH) consumption on the immune system in patients with alcoholic liver
      cirrhosis (ALC), as analyzed by the distribution of peripheral blood (PB-) T, B,
      and NK lymphoid subsets using multiple stainings with monoclonal antibodies and
      flow cytometry. For that purpose, we have analyzed a group of patients with ALC
      and active EtOH intake (ALCET group) which were re-evaluated 3 months after
      alcohol withdrawal. As controls, both ALC patients with at least 1 year of
      alcohol withdrawal (ALCAW group) and healthy subjects were used. Regarding the
      alcohol intake period, the most relevant findings were a significant activation
      of the PB T-cell compartment, and specifically of the TCR alpha beta + subset, as
      reflected by an increased expression of both the HLA DR and CD11c antigens as
      well as a significant increase of both the PB NK cells (CD3-/CD56+) and the
      cytotoxic T cells coexpressing the CD3 and CD56 molecules. In addition, a
      decrease of both the numbers of total B cells and their CD5+/CD19+ subset were
      observed. After a relatively short withdrawal period (3 months), the
      abnormalities of T, P, and NK cells disappeared. These findings suggest the
      existence of a close relationship between EtOH consumption and the abnormalities
      of the immune system observed during active alcoholism. Nevertheless, ALCAW
      individuals displayed marked alterations on the immunophenotypic profile, as
      reflected by a significantly decreased number of total T cells, due to reduced
      levels of the CD3+/TCR alpha beta+, CD4+, CD8+, and CD4+/CD45RA+ T-cell subsets.
      In addition, a significantly decreased number of total PB B cells was observed in
      this group of patients. Our results show that in patients suffering from ALC, the
      abnormalities of the immune system due to a direct effect of EtOH intake (or its
      metabolites) should be distinguished from the immunological alterations related
      to the liver disease itself.

PMID- 8986205
TI  - Ethnic differences in gastric sigma-alcohol dehydrogenase activity and ethanol
      first-pass metabolism.
AB  - We assessed whether the low sigma-alcohol dehydrogenase (ADH) activity in
      Japanese (compared with Caucasians) affects the first-pass metabolism of ethanol.
      ADH isozyme activities were determined in endoscopic biopsies of the gastric
      corpus from 24 Japanese and 41 Caucasian men by starch gel electrophoresis and by
      comparing the reduction of m-nitrobenzaldehyde (a preferred substrate of sigma
      ADH) with that of acetaldehyde (a preferred substrate of gamma-ADH) and the
      glutathione-dependent formaldehyde oxidation (a specific reaction of chi-ADH).
      Alcohol pharmacokinetics was compared in 10 Japanese and 10 Caucasians after
      administration of ethanol (300 mg/kg of body weight) intravenously or orally,
      using 5 and 40% oral solutions. Japanese exhibited lower sigma-ADH activity than
      Caucasians, with no difference in the other gastric isozymes. With 5% ethanol,
      first-pass metabolism was strikingly lower in Japanese than in Caucasians. Blood
      alcohol levels were similar because of the high elimination rate in Japanese due
      to the hepatic beta 2-ADH variant. With 40% ethanol, the first-pass metabolism
      increased in both groups to comparable levels, suggesting an additional
      contribution by chi-ADH at high ethanol concentrations. These results indicate
      that sigma-ADH activity contributes significantly to gastric ethanol oxidation
      and its lower activity in Japanese is associated with lesser first-pass
      metabolism.

PMID- 8986206
TI  - Models of treatment seeking for alcoholism: the role of genes and environment.
AB  - We investigated the relative influence of genes and environment on the decision
      to seek treatment for alcoholism under three models of health care utilization.
      Lifetime alcohol dependence and two measures of treatment seeking for alcohol
      problems were determined from a 1992 telephone administration of the Diagnostic
      interview Schedule. Data were analyzed from 1,864 monozygotic and 1,492 dizygotic
      male twin respondents from the Vietnam Era Twin Registry. Genetic and
      environmental contributions to the decision to seek treatment for alcoholism were
      assessed under competing models for the relationship between genetic influences
      on alcoholism risk and genetic influences on treatment seeking among those who
      became alcoholics. Under the best-fitting model, genetic influence accounted for
      41% of the variance in treatment seeking and 55% of the liability for alcoholism.
      Shared environment explained none of the variance in liability for alcoholism,
      but 40% of the variance in treatment seeking. The severity of alcoholism alone is
      an inadequate model of treatment seeking, because decisions to seek alcohol
      treatment are also influenced by substantial genetic and or shared environmental
      factors unrelated to the determinants of alcoholism.

PMID- 8986207
TI  - A PC-based software test for measuring alcohol and drug effects in human
      subjects.
AB  - A new software-based visual search and divided-attention test of cognitive
      performance was developed and evaluated in an alcohol dose-response study with 24
      human subjects aged 21-62 years. The test used language-free, color, graphic
      displays to represent the visuospatial demands of driving. Cognitive demands were
      increased over previous hardware-based tests, and the motor skills required for
      the test involved minimal eye movements and eye-hand coordination. Repeated
      performance on the test was evaluated with a latin-square design by using a
      placebo and two alcohol doses, low (0.48 g/kg/LBM) and moderate (0.72 g/kg/LBM).
      The data on 7 females and 17 males yielded significant falling and rising
      impairment effects coincident with moderate rising and falling breath alcohol
      levels (mean peak BrALs = 0.045 g/dl and 0.079 g/dl). None of the subjects
      reported eye-strain or psychomotor fatigue as compared with previous tests. The
      high sensitivity/variance relative to use in basic and applied research, and
      worksite fitness-for-duty testing, was discussed. The most distinct advantage of
      a software-based test that operates on readily available PCs is that it can be
      widely distributed to researchers with a common reference to compare a variety of
      alcohol and drug effects.

PMID- 8986208
TI  - Voices of the afflicted.
AB  - Over the past 10 years, I have been privileged to conduct educational forums for
      audiences containing many recovering alcoholics or otherwise chemically dependent
      persons. In these forums about the addictive diseases and their treatment and
      research possibilities, significant interaction with the audience members occurs.
      During these interactions, certain anecdotal phenomena seem to predominate. The
      repetitive nature of these reports suggests the need for systematic
      investigation. As with editorial comments in major medical journals, observed
      phenomena and unanswered questions from those afflicted can be valuable in the
      generation of testable hypotheses. Perhaps the ideas presented herein will be
      useful in the development of future research on alcohol abuse and alcohol
      dependence.

PMID- 8986209
TI  - Decreases in dopamine receptors but not in dopamine transporters in alcoholics.
AB  - It has been hypothesized that ethanol's actions on the dopamine (DA) system may
      participate in addiction. The purpose of this study was to evaluate the DA system
      in the brain of alcoholics. We evaluated 10 alcoholics and 17 nonalcoholics using
      positron emission tomography and [11C]raclopride to measure DA D2 receptors. In
      addition, in 5 of the alcoholics and 16 of the nonalcoholics, we also measured DA
      transporters with [11C]d-threo methylphenidate. The ratio of the distribution
      volumes in striatum to that in cerebellum, which corresponds to Bmax/Kd + 1, was
      used as model parameter of DA D2 receptor and transporter availability. Dopamine
      D2 receptor availability (Bmax/Kd) was significantly lower in alcoholics (2.1 +/-
      0.5) than in nonalcoholics (2.7 +/- 0.6) (p < 0.05) and was not correlated with
      days since last alcohol use. Alcoholics showed DA transporter values similar to
      those in nonalcoholics. The ratio of DA D2 receptor to transporter availability
      was significantly higher in nonalcoholics (1.4 +/- 0.1) than in alcoholics (1.1
      +/- 0.1) (p < 0.005). Alcoholics showed significant reductions in D2 receptors
      (postsynaptic marker) but not in DA transporter availability (presynaptic marker)
      when compared with nonalcoholics. Because D2 receptors in striatum are mainly
      localized in gamma-aminobutyric acid (GABA) cells these results provide evidence
      of GABAergic involvement in the dopaminergic abnormalities seen in alcoholics.

PMID- 8986210
TI  - Effects of bezafibrate on ethanol oxidation in rats.
AB  - Bezafibrate is used to lower serum lipid levels in humans. Fibrate derivatives
      induce an enzyme participating in the beta-oxidation by peroxisomes. We gave
      ethanol (2 g/kg) orally to bezafibrate-treated (300 mg/kg) male rats of the
      Wistar strain. Blood ethanol levels were remarkably lower and ethanol elimination
      stood at 432.6 mg/kg/hr (control, 336.6 mg/kg/hr) in the bezafibrate group (p <
      0.01). Blood acetate levels were conversely higher in the bezafibrate group. The
      fatty acid beta-oxidation activity of liver peroxisome in bezafibrate-treated,
      clofibrate-treated, or gamma-linolenic acid-treated rats for 4 days was assayed.
      The activity was 5.8-fold higher in rats given bezafibrate, 5.4-fold in the
      clofibrate (p < 0.01), and 2.0-fold in the gamma-linolenic acid (p < 0.05).
      Alcohol dehydrogenase and aldehyde dehydrogenase activity of cytosol in the liver
      was not induced by the hypolipidemic drugs, but aldehyde dehydrogenase activity
      in the liver homogenate was induced. From foregoing results, bezafibrate induced
      in the organism beta-oxidation by peroxisomes and increased H2O2 production,
      which led to augmented ethanol metabolism by catalase.

PMID- 8986211
TI  - Sensitivity to ethanol-induced ataxia in HOT and COLD selected lines of mice.
AB  - Studies with inbred strains of mice have suggested that there may be a genetic
      correlation between strain sensitivities to the ataxic and hypothermic responses
      to ethanol (EtOH), which would suggest that some genes influence both responses.
      To test this hypothesis, EtOH sensitivity was determined in replicate lines of
      mice selectively bred for sensitivity (COLD) or resistance (HOT) to acute ethanol
      hypothermia. Several tests were used to index ataxia, related traits such as
      muscle strength, and locomotor activity. The screen test yielded a dose-dependent
      EtOH-induced decrease in performance that did not differ between the selected
      lines. Based on the dose-response characteristics of this task, 2.5 g/kg of EtOH
      was used as the test dose for the remaining experiments. Results from the fixed
      speed rotarod and the grid test of motor incoordination also indicated no
      significant differences between HOT and COLD mice in sensitivity to EtOH
      impairment. When the selected lines were tested on an accelerating rotarod, COLD
      mice were impaired by the acute EtOH injection, but HOT mice were unaffected.
      COLD mice were more sensitive to EtOH-induced decrements in grip strength and
      locomotor activity. Overall, the results indicated that HOT and COLD mice were
      only differentially sensitive to EtOH in some tasks related to ataxia, suggesting
      that some genes must be associated uniquely with EtOH-induced hypothermia or
      ataxia. The mixed results from the various tests indicate that ataxia can best be
      conceived as a group of related complex behaviors that cannot be assessed
      adequately by the use of a single task and that ataxia-related behaviors are
      influenced by different groups of genes.

PMID- 8986212
TI  - Long-term effects of chronic ethanol on muscarinic receptor binding in rat brain.
AB  - Effects of chronic ethanol treatment (CET) on muscarinic acetylcholine receptor
      (mAChR) binding properties were investigated via quantitative autoradiography in
      rats maintained on an ethanol-containing liquid diet for 28 weeks and withdrawn
      from ethanol for 8 weeks before harvesting of tissues. Controls received an
      identical diet in which sucrose was substituted isocalorically for ethanol.
      Maximal binding of the radiolabeled mAChR antagonist quinuclidinyl benzilate
      ([3H]QNB) was not reduced in hippocampal area CA1, dentate gyrus, neocortex,
      striatum, or thalamus, suggesting that CET results in no significant mAChR loss
      in these regions. Binding affinities of the cholinergic agonist carbachol to
      mAChRs were unaffected by CET in each of these regions, as determined by
      competitive displacement of [3H]QNB labeling. These results suggest that CET
      induced functional deficits in brain cholinergic responses are not due to direct
      effects of CET on mAChR binding properties.

PMID- 8986213
TI  - The role of nitric oxide in ethanol-induced gastrointestinal dysfunction.
AB  - We recently showed that acute ethanol inhibits contractility of the lower
      esophageal sphincter (LES) and the lower esophageal body (LEB) both in vivo and
      in vitro. To evaluate the mechanism of this inhibitory effect of ethanol, we
      investigated the role of nitric oxide (NO) on contractility of isolated LES and
      LEB circular muscle strips using inhibitors of NO synthase (NOS), NG-nitro-L
      arginine methyl ester and NG-nitro-L-arginine. Ethanol significantly decreased
      LES basal tone. This effect was not mediated by NO, because inhibition was not
      prevented by inhibitors of NOS. Electrical field stimulation caused an On
      response relaxation from LES strips, and an Off-response contraction from both
      LES and LEB strips. Inhibitors of NOS prevented the On-response relaxation of
      LES, but had no significant effect on LES Off-response contraction. Ethanol
      potentiated the On-response relaxation of the LES Off-response contraction.
      Ethanol potentiated the On-response relaxation of LES, but had no significant
      effect on Off-response contraction. Ethanol's potentiating effect of the On
      response relaxation is NO-mediated, because it was abolished by NOS inhibitors.
      Ethanol also inhibited carbachol-induced LES contractility. This inhibitory
      affect was NO-mediated, because NOS inhibitors abolished it. Ethanol inhibited
      both the Off-response contraction and carbachol-induced contraction of LEB
      strips. These effects were not NO-mediated, because they were not affected by NOS
      inhibitor. These data suggest that NO is not a mediator for the inhibitory effect
      of ethanol on LEB contractility, and that NO seems to be a mediator of ethanol
      inhibition of some aspects of LES motor functions.

PMID- 8986214
TI  - Human hepatocyte growth factor in alcoholic liver disease: a comparison with
      change in alpha-fetoprotein. Department of Veterans Affairs Cooperative Study
      Group 275.
AB  - To evaluate the hepatic regenerative response in patients with alcoholic liver
      disease, sera from 263 patients with severe alcoholic hepatitis and/or cirrhosis
      were analyzed for hepatocyte growth factor (HGF) and alpha-fetoprotein (AFP). HGF
      concentration was elevated above healthy controls in 95% of the patients (median
      level = 2.4 ng/ml), whereas AFP tended to be depressed below controls (median
      level = 4.1 ng/ml). Correlations with parameters of liver injury (i.e., ascites,
      encephalopathy, AST bilirubin, and protime) all showed a more significant
      correlation with HGF concentrations than those of AFP. Patients with HGF levels
      below the mean (4 ng/ml) exhibited significantly better survival (median survival
      = 35 months vs. 8.5 months for those with HGF > or = 4 ng/ml; p = 0.007). Serum
      HGF levels were associated with various specific histologic features of alcoholic
      hepatitis that included, but were not exclusively related to, necrosis.

PMID- 8986215
TI  - Dopamine receptors in the medial prefrontal cortex influence ethanol and sucrose
      reinforced responding.
AB  - This study tested the role of dopamine receptors in the medial prefrontal cortex
      (mPFC) in the onset, maintenance, and termination of ethanol and sucrose
      reinforced responding. Two groups of Long Evans rats were trained to lever press
      on a fixed-ratio 4 schedule of reinforcement with 10% ethanol (n = 10) or 5%
      sucrose (n = 5) presented as the reinforcer. After implantation of injector guide
      cannulae, the D2/3 agonist quinpirole and the D2 antagonist raclopride were
      administered bilaterally into the mPFC before behavioral sessions. During control
      conditions, sucrose reinforcement maintained a 2-fold greater number of responses
      per session than did ethanol reinforcement. Quinpirole (10.0
      micrograms/microliter) reduced total ethanol-reinforced responses by delaying
      response onset and decreasing the duration of responding, but had no effect on
      response maintenance (i.e., response rate). A higher dose of quinpirole (20.0
      micrograms/microliter) decreased total sucrose responses by simultaneously
      decreasing duration and response rate, without altering response latency. Thus,
      the effects of quinpirole on ethanol and sucrose-reinforced responding were
      similar on response total and duration, but differential on response latency and
      rate. Raclopride (0.05 and 1.0 microgram/microliter) decreased total ethanol
      responding and rate, but doses as much as 400-fold greater (20.0
      micrograms/microliter) did not alter sucrose response totals. Raclopride alone
      had no effect on response latency or duration measures in either reinforcement
      condition. Coadministration of raclopride blocked the quinpirole-induced increase
      in response latency (ethanol reinforcement) and decrease in response rate
      (sucrose reinforcement), but had no effect on other response measures. These data
      are consistent with the interpretation that D2 and D3 receptors in the mPFC are
      differentially involved in ethanol and sucrose response onset and maintenance,
      but similarly involved in response termination. However, differences in baseline
      response parameters and group size may have contributed to the observed effects.

PMID- 8986217
TI  - Ethanol ingestion impairs neutrophil bactericidal mechanisms against
      Streptococcus pneumoniae.
AB  - Ethanol ingestion impairs both killing of selected pneumococcal strains by rat
      polymorphonuclear leukocytes (PMNL) in vitro and clearance of these same strains
      from experimentally infected rat lungs. To determine the mechanism(s) of this
      impairment, we isolated neutrophils (PMNL) by a magnetic cell sorting technique
      from the peripheral blood of chow-fed rats (C-PMNL) or rats pair fed for 7 days
      with a liquid diet providing 36% of its calories as either ethanol (E-PMNL) or
      dextrin-maltose (P-PMNL). Phagocytosis of fluorochrome-labeled bacteria and
      oxygen radical production, as determined by oxidation of dihydrorhodamine 123,
      were measured by flow cytometry. Degranulation, as determined by lysozyme
      release, was measured as lysis of a suspension of Micrococcus lysodeikticus. E
      PMNL, P-PMNL, and C-PMNL were equivalent in their ability to phagocytose
      pneumococci and to produce an oxidative burst in response to stimulation by
      opsonized zymosan. However, E-PMNL produced fewer oxygen radicals and released
      less lysozyme than either P-PMNL or C-PMNL when stimulated by exposure to S.
      pneumoniae. There was no difference in oxygen radical production by E-PMNL and P
      PMNL when stimulated with phorbol myristate acetate, but both cell types mounted
      a significantly reduced response in comparison to C-PMNL. These data suggest that
      ingestion of ethanol for 7 days significantly reduces both the oxidative burst
      and degranulation of rat PMNL in response to S. pneumoniae, thereby compromising
      anti-pneumococcal activity.

PMID- 8986216
TI  - Alcohol and cytokine-inducible transcription factors.
AB  - Cytokines, such as TNF alpha, modulate the behavior of many cells by regulating
      the expression of a wide array of genes. When a cytokine binds to its receptor on
      the cell surface, the receptor becomes activated and activates signal
      transduction cascades. These cascades typically involve a series of
      phosphorylation reactions that lead to sequential activation of various kinases.
      The targets of these kinases include DNA binding proteins that regulate the
      transcription of target genes. The activity of DNA binding proteins, such as c
      Jun and NF-kappa B, titrates the transcriptional activity of cytokine-regulated
      genes. Both acute and chronic alcohol consumption of ethanol increase hepatic
      expression of TNF alpha. After acute ethanol consumption, this is associated with
      increased induction of several TNF-dependent regenerative events, including the
      activation of c-Jun and increased binding activity of NF-kappa B. However,
      chronic consumption of ethanol appears to impede TNF alpha signaling in the liver
      because it attenuates the increases in c-JUN activity and NF-kappa B binding,
      which normally follow partial hepatectomy. These results suggest that one
      mechanism by which ethanol influences liver cell behavior is by influencing local
      expression of TNF alpha and changing the activity of TNF-regulated transcription
      factors.

PMID- 8986218
TI  - Effect of chronic ethanol consumption on the atrial natriuretic system of
      spontaneously hypertensive rats.
AB  - There is a lot of discussion on the effects of ethanol (ETOH) on blood pressure
      (BP). It has been suggested that chronic moderate ETOH consumption prevents the
      development of age-dependent hypertension in humans and spontaneously
      hypertensive rats (SHR). However, the mechanism mediating this effect is unknown.
      In the present studies, we hypothesized the implication of atrial natriuretic
      peptide (ANP), a BP-lowering hormone, on the antihypertensive effect of moderate
      ETOH consumption. A 20% v/v solution of alcohol was given as drinking fluid to
      SHR and normotensive Wistar-Kyoto (WKY) rats for up to 32 weeks. This treatment
      prevented, at least in part, the age-dependent increase of BP in SHR and WKY
      rats. The lower BP was associated with significantly lower levels of circulating
      atrial natriuretic peptide in both groups. After chronic ETOH administration,
      total ANP content and concentration were higher in the left and right atria of
      SHR and WKY rats than in water-treated controls. Despite the ETOH-induced
      increase in atrial ANP content, there was no significant change in atrial ANP
      mRNA, suggesting decreased atrial release. Chronic ETOH treatment significantly
      reduced ANP mRNA in the ventricles of SHR but not of WKY rats. Correspondingly,
      ventricular ANP content and concentration were lowered by ETOH in SHR only.
      Chronic ETOH administration induced a significant increase of plasma arginine
      vasopressin and a significant decrease of plasma aldosterone in SHR but not in
      WKY rats. Thus, chronic ETOH treatment prevented the age-dependent elevation of
      BP in both SHR and WKY rats and altered the activity of heart ANP as well as of
      the aldosterone and plasma arginine vasopressin systems.

PMID- 8986219
TI  - Prenatal ethanol exposure alters the expression of intestinal hydrolase mRNAs in
      newborn rats.
AB  - To gain insight into the postnatal growth delay induced by ethanol in utero, we
      characterized functional impairments of the small intestine of neonatal rats
      prenatally exposed to ethanol using a well-described model of gestational
      alcoholism (25% ethanol w/v in the drinking water). Expression of the intestinal
      enzymes-lactase-phlorizin hydrolase (LPH) and intestinal alkaline phosphatase
      (IAP)-that are critical for enteral nutrition of neonates was studied.
      Characteristic patterns of LPH and IAP expression along the proximal-distal
      (horizontal) and crypt-villus (vertical) axes of the small intestine, as well as
      the intracellular localization of LPH and IAP mRNAs and immunoreactive proteins
      within absorptive enterocytes, were not altered by prenatal exposure to ethanol.
      However, a 10- to 15-fold increase in the number of LPH and IAP mRNA molecules
      per absorptive enterocyte was found throughout the intestine of ethanol-exposed
      neonates, compared with controls, whereas lactase and alkaline phosphatase
      activities per enterocyte remained unchanged. These findings suggest that ethanol
      in utero alters the mRNA abundance of epithelial enzymes in newborn rat small
      intestine. Changes in mRNA abundance could be an important aspect of enterocyte
      adaptation to high ethanol concentrations in gastrointestinal amniotic fluid of
      ethanol-exposed fetuses.

PMID- 8986221
TI  - Acute hemodynamic, pituitary, and adrenocortical responses to alcohol in adult
      female sheep.
AB  - Alcohol was infused intravenously into chronically cannulated adult female sheep
      as a 40% solution (w/v) at doses of 0.5, 1.0, 1.5, or 2.0 g/kg over 1 hr. Saline
      infusions, equal in volume to the highest dose, served as a control. Dose
      dependent peak blood alcohol concentrations (BACs) were attained 60 min after the
      beginning of alcohol infusion for all doses (86.5 +/- 3.7, 213.2 +/- 11.0, 373.2
      +/- 14.3, and 494.1 +/- 34.5 mg/dl +/- SE, respectively). Plasma cortisol
      concentrations increased in response to the 0.5 g/kg infusions (BACs less than
      100 mg/dl), whereas both ACTH and cortisol concentrations increased in the 1.0
      and 2.0 g/kg dose groups. Mean arterial pressure, heart rate, and Paco2
      increased, whereas Pao2 decreased in response to the 1.5 and 2.0 g/kg infusions.
      Arterial pH declined in the highest dose group. Respiratory rate was lower in all
      groups receiving alcohol compared with that of the control group. Hematocrit did
      not change. We conclude that BACs in adult female sheep below 100 mg/dl (levels
      easily achieved by social drinkers) result in activation of the hypothalamus
      pituitary-adrenal axis. At high BACs (> 350 mg/dl), pituitary adrenal responses
      are accompanied by increases in heart rate, blood pressure, and Paco2 and
      decreases in Pao2 and arterial pH. These findings support the hypothesis that
      alcohol acts directly on the brain to mediate pituitary adrenal responses and
      that the additional responses to high BACs (the blood gas and hemodynamic
      responses), might be mediated by direct actions of alcohol on the brain, by
      cerebral ischemia, or by alcohol-mediated suppression of ventilatory drive and
      hypoxemia.

PMID- 8986222
TI  - Noncompetitive-like inhibition of ethanol elimination by cyanamide treatment:
      pharmacokinetic study.
AB  - The effect of acetaldehyde accumulation of ethanol elimination is of interest in
      medico-legal practice in Japan. We examined the pharmacokinetic mechanism of the
      inhibition of ethanol metabolism by cyanamide, an inhibitor of mitochondrial
      aldehyde dehydrogenase. An ethanol solution (0.25-2.0 g/kg body weight) was
      injected intravenously into male rabbits with or without administration of
      cyanamide. Cyanamide was injected intraperitoneally (25 mg/kg body weight) to the
      cyanamide-treated group 2 hr before ethanol injection. Blood ethanol and
      acetaldehyde concentrations were measured periodically by head-space gas
      chromatography. The MULTI(RUNGE) computer program was applied for the
      pharmacokinetic analysis. One- or two-compartment open models with Michaelis
      Menten elimination kinetics were used for simultaneous multi-line fitting. The
      ethanol elimination rate decreased by cyanamide treatment. The border-point
      concentration between pseudolinear and curvilinear phases was not affected by
      cyanamide treatment. The estimated Vmax value decreased by cyanamide treatment,
      whereas the K(m) value did not change. Our results correspond to a noncompetitive
      like inhibition of ethanol metabolism. K(m) is related to the border point
      between pseudolinear and curvilinear phases. Thus, our findings in the blood
      ethanol concentration-time curve suggest adequate curve-fitting. The product, or
      competitive, inhibition of alcohol dehydrogenase by acetaldehyde had been
      reported in enzymological study. The pharmacokinetic manner of inhibition in vivo
      was different from the enzymologic mechanism in vitro. Other metabolic factors
      related to ethanol metabolism are thought to be more important than acetaldehyde
      accumulation itself.

PMID- 8986220
TI  - Norepinephrine and serotonin receptors in the paraventricular nucleus
      interactively modulate ethanol consumption.
AB  - The homeostatic function of the hypothalamus has long been recognized. In
      particular, the role of the paraventricular nucleus (PVN) in regulating ingestive
      behavior has been of interest. Infusions of serotonin and norepinephrine into the
      PVN are correlated with nutrient selective decreases and increases in consumatory
      behavior, respectively. Given the wide range of homeostatic functions of the
      hypothalamus, it is plausible that similar hypothalamic mechanisms may also be
      involved in the regulation of ethanol intake. This study examined the effects of
      PVN infusions of serotonin (5-HT) and norepinephrine (NE) on ethanol intake in a
      1-hr limited-access two-bottle paradigm. When intake of 6% (v/v) ethanol versus
      water stabilized, male Wistar rats were implanted with stainless steel guide
      cannulae aimed at the PVN. After recovery, NE (20, 50, and 100 nmol), 5-HT (5 and
      25 nmol), and their combination (NE 50 nmol + 5-HT 5 nmol) were microinjected
      into the PVN in a volume of 0.5 microliter/side over 1 min. Baseline ethanol
      intake was approximately 1.0 g/kg and ethanol preference (milliliters ethanol per
      total milliliters) was approximately 60%. Both 20 and 50 nmol of NE significantly
      increased absolute ethanol intake by 50% and relative ethanol intake by
      approximately 30%. Corresponding decreases were observed in water intake. Neither
      dose of 5-HT when administered alone altered ethanol or water consumption, but
      the 5-nmol dose of 5-HT attenuated the increase observed after NE (50 nmol)
      administration. These data demonstrate that NE and 5-HT receptors in the PVN
      interact in the modulation of ethanol ingestion. This finding suggests that
      homeostatic regulatory functions of the hypothalamus are involved in ethanol
      intake, and a perturbation of this system may influence excessive drinking.

PMID- 8986223
TI  - Mitochondrial ALDH polymorphism affects ethanol-derived acetate disposition in
      Wistar rats.
AB  - We studied the relationship between polymorphism of aldehyde dehydrogenase (ALDH)
      and ethanol and acetate kinetics in male Wistar rats. Blood ethanol and acetate
      concentration time curves after intravenous bolus administration of 1 g/kg of
      ethanol were estimated by moment analysis. ALDH isozymes in hepatic subcellular
      fractions were detected by isoelectric focusing (IEF). Blood acetate profiles
      were divided into two patterns: one-peak type and two-peak type. IEF studies on
      ALDH isozymes in subcellular fractions showed polymorphism of cytosolic and
      mitochondrial ALDHs. Polymorphism patterns of ALDH2 corresponded with patterns of
      blood acetate profiles. Significant differences in mean residence time of acetate
      and the ratio of area under curves (AUCs) of acetate to ethanol
      (AUCacetate/AUCEtOH) occurred between different IEF patterns of mitochondrial low
      K(m) ALDH (ALDH2). Therefore, it was clarified that ALDH2 polymorphism affects
      ethanol-derived acetate disposition in Wistar rats. Similarity of AUC values of
      acetate considered, these observations suggest that ALDH2 polymorphism results in
      change of effects of acetate and acetate-generated adenosine on the central
      nervous system and other organs during chronic ethanol consumption.

PMID- 8986224
TI  - Genotypes of alcohol-metabolizing enzymes and the risk for alcoholic chronic
      pancreatitis in Japanese alcoholics.
AB  - Genetic predisposition to alcoholism and alcoholic liver disease has been
      reported. However, genetic susceptibility to alcoholic pancreatitis is still a
      matter of debate. To determine it, we examined genotype patterns of aldehyde
      dehydrogenase (ALDH2), alcohol dehydrogenase (ADH2 and ADH3), and cytochrome P
      4502E1 (CYP2E1) in alcoholic pancreatitis patients. In 296 alcoholic patients, 52
      cases showed findings of chronic pancreatitis by ultrasonography and x-ray
      computed tomography and/or had a history of pancreatitis (P+). The remaining 244
      patients had neither abnormal findings of the image examinations nor a history of
      pancreatitis (P-). As for the ADH2 genotype, distribution of 2(1)/2(1),
      2(1)/2(2), and 2(2)/2(2) was 22, 37, and 42% in P+ patients, whereas 34, 35, and
      30% in P- patients, respectively. The frequency of ADH2(2)/2(2) genotype was
      significantly higher in P+ patients, compared with that in P- patients. There
      were no significant differences in the distribution of ADH3, ALDH2, and CYP2E1
      genotypes between P+ and P- patients. In 14 alcoholic patients who showed low
      contents of fecal chymotrypsin, which suggests dysfunction of pancreatic
      exocrine, the rate of ADH2(2)/2(2) genotype also tended to be higher (50%) than
      in 74 controls who showed normal contents of the fecal chymotrypsin (28%). No
      differences were observed in genotypes of ADH3, ALDH2, and CYP2E1. Moreover, the
      frequency of ADH2(2)/2(2) genotype was significantly higher in autopsy cases with
      interlobular fibrosis in the pancreas, which suggests alcoholic pancreatic
      damage, than in cases with only intralobular pancreatic fibrosis. These data
      suggest that the risk of alcoholic pancreatitis seems to be associated with the
      presence of ADH2(2)/2(2) genotype.

PMID- 8986225
TI  - Investigation of genetic risk factors associated with alcoholism.
AB  - Alcoholism is a multifactorial disease influenced by genetic-environmental
      interaction. Genetic variation of the receptor may be associated with alcohol
      dependence due to its modified function in behavioral and physiological
      responses. In the present study, polymorphic alleles of cholecystokinin B
      receptor (CCKBR), serotonin 1A receptor (HT1AR) genes, and mitochondrial DNA were
      analyzed. DNAs were isolated from the blood samples of 112 healthy controls and
      106 alcoholics. Genetic variation was detected by SSCP analysis, followed by
      direct sequencing of polymerase chain reaction product as well as restriction
      fragment-length polymorphism. Three different mutations were found in the exon 3
      sequence of CCKBR: His (CAT) at aa207-->His (CAC) (5.4%), Arg (CGC) at aa215-
      >His (CAC) (4.5%), and Val (GTG) at aa138-->Met (ATG) (0.9%) in controls.
      Genotypic distribution of alcoholics was not significantly different with that in
      controls. A proline (CCG) to leucine (CTG) substitution at amino acid 16 of HT1AR
      was found in alcoholics (4.5%) and in controls (4.7%). This mutation site of
      HT1AR was different in comparison with the variants reported by Nakhai et al.
      (Biochem Biophys. Res. Commun. 210:530-536, 1995). Analysis of the mitochondrial
      DNA showed that a 491 bp deletion in the sequence of ATPase exists as
      heteroplasmy in 58% of alcoholics, but not in controls. Heteroplasmic deletion of
      mitochondrial DNA may be a useful marker for alcohol abuse. Further study is
      undergoing to elucidate the cause and significance of this deletion in
      alcoholics.

PMID- 8986226
TI  - Effect of alcohol drinking on gene expression of hepatic O6-methylguanine DNA
      methyltransferase in chronic liver diseases.
AB  - O6-methylguanine DNA methyltransferase (MGMT) is a repair protein that transfers
      methyl groups from O6-methylguanine to a cysteine acceptor in its own molecule,
      and restores DNA to its undamaged state. If left unrepaired, O6-methylguanine can
      pair with either a thymine or a cytosine, causing a C-G to T-A transition, which
      is considered to be one of the molecular mechanisms of both mutagenesis and
      carcinogenesis. The expression of MGMT mRNA in liver tissue was quantitatively
      assessed by the competitive reverse transcription-polymerase chain reaction
      method in patients with chronic liver diseases with or without alcohol drinking.
      MGMT mRNA expression was 1.4 +/- 0.9 pg/micrograms RNA in control livers. Its
      expression in chronic hepatitis was 3.8 +/- 0.7 in alcoholics and 2.7 +/- 0.8 in
      nonalcoholics, which were not statistically different. MGMT mRNA expression in
      liver cirrhosis was significantly low, compared with that in chronic hepatitis,
      and 0.8 +/- 0.3 in alcoholics and 0.5 +/- 0.1 in nonalcoholics, which also were
      not significantly different. The present study shows that MGMT mRNA was not
      decreased in patients with chronic liver diseases with alcohol drinking, compared
      with those without alcohol drinking.

PMID- 8986227
TI  - Alteration of glutamyltranspeptidase binding proteins in postmortem brains of
      heroin addicts.
AB  - Glutamyltranspeptidase binding (G) proteins play an important role in
      intracellular signal transduction downstream from many receptors, including
      opioid receptors. Moreover, it was recently reported that the beta-subunits of G
      proteins, in addition to the alpha-subunits, regulate effector pathways. In this
      study, membrane G protein immunoreactivity was estimated by Western blotting with
      polyclonal antibodies (RM/1, AS/7, GC/2, QL, and SW/1) against specific G
      proteins (G alpha S, G alpha i-1,2, G alpha o, G alpha q, and G beta,
      respectively) in postmortem temporal cortex obtained from 6 heroin addicts and 6
      control subjects without a history of drug abuse. Immunoreactivities of the G
      beta-subunit increased significantly (p < 0.05) in heroin addicts, compared with
      controls, and that of G alpha i-1,2 tended to increase in heroin addicts. Present
      findings suggest that the alterations in G protein-mediated signal transduction
      may be involved in the mechanism of opiate addiction.

PMID- 8986228
TI  - Effects of ethyl alcohol administration to THA rat dams during their gestation
      period on learning behavior and on levels of monoamines and metabolites in the
      brain of pups after birth.
AB  - Children born from chronic alcoholic mothers have shown behavioral teratogenic
      effects more frequently than morphological malformations. To investigate the
      possible mechanisms and evaluate maternal alcohol dosage levels to induce
      behavioral dysfunctions, we gave pregnant Tokai High Avoider (THA) rats 0, 5, 10,
      and 20% ethanol (EtOH) as drinking water during the gestation period. We
      evaluated the brain function of pups born of alcohol-administered dams. Sidman
      avoidance behavior test and the levels of monoamines (nor-adrenalin, dopamine,
      and serotonin) and metabolites (3, 4-dihydroxyphenyl acetic acid, homovanillic
      acid, and 5-hydroxyindole acetic acid) in whole brain were examined for
      neurobehavioral and neurochemical effects. EtOH-exposed THA offsprings showed
      high pre- and postnatal mortality, growth deficits, and brain weight reductions.
      Compared with the results of the same conditioning experiment using Wistar rats,
      the THA rat may have higher susceptibility to the effects of in utero EtOH
      exposure than Wistar rats. EtOH-exposed THA pups exhibited deficits in avoidance
      operant learning that were not shown in Wistar rats. We also observed the
      increased levels of all monoamines that were assumed to be related with the
      deficit of learning, the decreased levels of 3, 4-dihydroxyphenyl acetic acid and
      homovanillic acid, and the unchanged levels of 5-hydroxyindole acetic acid in
      pups from dams administered 10 and 20% EtOH. However, contrary alteration of
      monoamines and their metabolites were shown in pups from 5% EtOH-administered
      dams.

PMID- 8986229
TI  - Possibility of 5-HT3 receptor involvement in alcohol dependence: a microdialysis
      study of nucleus accumbens dopamine and serotonin release in rats with chronic
      alcohol consumption.
AB  - The present study was performed to examine the involvement of serotonin-3 (5-HT3)
      receptors in the rat nucleus accumbens (ACC) in alcohol dependence. In alcohol
      treated rats, perfusion of 40 mM K+ and 100 mM ethanol (EtOH) through the
      microdialysis probe increased the extracellular levels of ACC dopamine (DA),
      compared with controls. Perfusion of the serotonin (5-HT) uptake inhibitor
      sertlarine enhanced the extracellular levels of ACC 5-HT in both groups.
      Increased 5-HT availability in the synaptic clefts on the ACC further activated
      ACC DA release in the alcohol-treated rats, in comparison with controls. In the
      final experiments, perfusion of the 5.0 microM 5-HT3 receptor agonist 2-methyl-5
      HT (2-Me-5-HT) through the microdialysis probe enhanced the extracellular levels
      of ACC DA. Magnitude of 2-Me-5-HT-induced DA release was significantly higher in
      alcohol-treated rats than in controls. On the other hand, 40 mM K(+)- and 100 mM
      EtOH-induced extracellular 5-HT release in alcohol-treated rats were markedly
      inhibited. These results show that (1) chronic alcohol intake increases the
      sensitivity of 5-HT3 receptors, (2) 5-HT3 receptors regulate DA release in the
      ACC, (3) the dopaminergic neuronal systems associated with 5-HT3 ionophore in the
      ACC were upregulated after chronic alcohol exposure, and (4) chronic alcohol
      intake desensitizes the serotonergic neuronal systems in rat ACC. These findings
      suggest that neurochemical functions of 5-HT3 receptors in regulating DA release
      in the ACC after alcohol exposure compensate for the dysfunction of serotonergic
      activity to restore the original properties in processing alcohol tolerance and
      that the development of alcohol dependence may be mediated by ACC 5-HT3
      receptors.

PMID- 8986230
TI  - Interaction of protein phosphatases and ethanol on phospholipase C-mediated
      intracellular signal transduction processes in rat hepatocytes: role of protein
      kinase A.
AB  - Phospholipase C (PLC)-mediated signal transduction processes in rat hepatocytes
      are subject to modulation by protein phosphatases (PPases) and protein kinases,
      including protein kinase A (PKA) and protein kinase C. Ethanol (EtOH) stimulates
      PLC activity in liver cells in the absence of hormones, and EtOH pretreatment
      inhibits the subsequent stimulation of PLC by hormonal stimuli. There is evidence
      that protein kinase activities are involved in these actions of EtOH. We
      investigated the effects of okadaic acid (OKA), a PPase inhibitor, and 8-(4
      chlorophenylthio)adenosine 3':5'-cyclic monophosphate (cpt-cAMP), a cell permeant
      cAMP analog that activates PKA, on EtOH-induced PLC activation. In addition, we
      studied the combined effects of cpt-cAMP and EtOH/OKA on vasopressin-induced PLC
      activation. PLC activation (cytosolic Ca2+ mobilization and inositol
      trisphosphate accumulation) induced by EtOH and vasopressin was inhibited by
      treatment with OKA, and was potentiated by cpt-cAMP. OKA treatment prevented the
      effect of cpt-cAMP. Pretreatment with EtOH caused inhibition of vasopressin
      induced PLC activation. EtOH also decreased the enhancing effect of cpt-cAMP on
      the responses to vasopressin. The susceptibility to enhancement by cpt-cAMP
      plotted as a function of the initial rate of vasopressin-induced Ca2+
      mobilization in EtOH-treated cells was similar to the pattern observed in OKA
      treated cells. These data suggest that interactions of OKA and PKA on EtOH
      induced PLC activation occurred at the level of G-protein, and indicate that EtOH
      may act as an inhibitory agent of PPase.

PMID- 8986231
TI  - Effect of glutathione on inositol 1,4,5-triphosphate-induced Ca2+ release in
      permeabilized hepatocytes from control and chronic ethanol-fed rats.
AB  - The effect of oxidized and reduced glutathione on inositol 1,4,5-trisphosphate
      (InsP3)-induced Ca2+ release from endoplasmic reticular Ca2+ stores was studied
      in digitonin-permeabilized hepatocytes from chronically ethanol-fed rats and pair
      fed control animals. The fractional Ca2+ release induced by a subsaturating
      concentration of InsP3 was significantly enhanced in cells from ethanol-fed rats
      in the absence of a change in maximal InsP3-releasable Ca2+ pool size, and this
      difference was not affected by preincubation with reduced glutathione. Incubation
      with oxidized glutathione (1 mM) increased the efficacy of Ca2+ release by
      subsaturating concentrations of InsP3 in both control preparations and in cells
      from ethanol-fed rats. The shift in the InsP3 dose-response curve was not
      significantly different between the two preparations. These findings suggest that
      the enhanced efficacy of InsP3-induced Ca2+ release in hepatocytes from ethanol
      fed rats is not caused by the oxidation of protein-bound thiol groups on the
      InsP3 receptor.

PMID- 8986232
TI  - Inhibitory effect of ethanol on hepatocyte growth factor-induced DNA synthesis
      and Ca2+ mobilization in rat hepatocytes.
AB  - Hepatocyte growth factor (HGF) is the most potent mitogen identified for
      hepatocytes and is thought to be an important growth factor in the regulation of
      liver regeneration. Its effects are mediated through a tyrosine kinase receptor,
      the product of c-met proto-oncogene. One of the downstream signaling processes
      activated by HGF is phospholipase C-gamma. HGF stimulation of liver cells causes
      formation of inositol 1,4,5-triphosphate, which releases Ca2+ from intracellular
      Ca2+ ([Ca2+]i) stores, and causes elevation of cytosolic Ca2+ levels. It is known
      that liver regeneration is inhibited by both acute and chronic ethanol (EtOH)
      treatment. We investigated the effect of EtOH on HGF-induced DNA synthesis and
      mobilization of [Ca2+]i in rat hepatocytes in primary culture. DNA synthesis was
      monitored by [3H]thymidine incorporation in primary cultures of hepatocytes 42 hr
      after stimulation with HGF. HGF concentration required for maximum DNA synthesis
      was 0.3 to 1 ng/ml, and DNA synthesis was inhibited by 100 mM EtOH at HGF
      concentrations in the range of 0.1 to 5 ng/ml. This inhibition was strongest (45
      to 47% inhibition) at a low concentration of HGF (0.1 to 0.3 ng/ml) and decreased
      at an HGF concentration > 1 ng/ml. HGF-induced changes in [Ca2+]i were measured
      in single fura 2-loaded hepatocytes by fluorescence imaging techniques. The Ca2+
      response induced by HGF (0.3 to 5 ng/ml) was inhibited by EtOH, with an EC50 of
      approximately 50 mM. Analysis of Ca2+ response patterns in individual cells
      indicated that EtOH suppressed the number of responsive cells and made Ca2+
      responses more transient, but did not affect peak [Ca2+]i elevation; thus
      suggesting an inhibition at the level of phospholipase C-gamma-activation. These
      data indicate that inhibition by EtOH of the response of liver cells to HGF may
      contribute to the inhibitory effect of EtOH on liver regeneration.

PMID- 8986233
TI  - Role of Kupffer cell-derived reactive oxygen intermediates in alcoholic liver
      disease in rats in vivo.
AB  - The pathophysiology of alcoholic liver disease (ALD) remains largely unknown. In
      this work, we have developed an experimental rat model to elucidate the mechanism
      of liver injury, including ALD, in which Kupffer cell-derived reactive oxygen
      intermediates (ROIs) might be involved. Groups of male Wistar rats were pair-fed
      on a liquid high-fat diet containing ethanol (36% of total calories) or
      isocaloric carbohydrate with or without dietary carbonyl iron (0.5% w/v) for 3
      weeks. In this rat model, we investigated Kupffer cell-derived ROI generation,
      which affected hepatocellular injury and hepatic fibrosis in ALD. The production
      of ROIs in Kupffer cells isolated from the iron-fed, the ethanol-fed, and the
      ethanol plus iron-fed rats were significantly increased, compared with that in
      Kupffer cells isolated from control rats (iron > ethanol+iron > ethanol > >
      control). However, hepatic vitamin E content in the ethanol plus iron-fed rats
      was decreased rather than that in the iron-fed rats. Then, lipid peroxidation of
      isolated microsomes was assessed as malondialdehyde equivalents determined by
      thiobarbituric acid assay. Compared with controls, the malondialdehyde
      equivalents were elevated in experimental groups (ethanol+iron > ethanol > iron >
      control). Serum ALT levels were greatly elevated in rats fed a diet containing
      both ethanol and iron (ethanol+iron > iron > ethanol > control). Hepatic content
      of hydroxyproline was significantly increased in ethanol plus iron-fed rats,
      compared with rats other than the ethanol plus iron-fed group (ethanol+iron >
      iron > ethanol > control). These results suggested that the enhanced Kupffer cell
      derived ROI generation could itself contribute to the increased susceptibility to
      lipid peroxidation, which might cause hepatocellular injury and lead to hepatic
      fibrosis in ALD.

PMID- 8986234
TI  - Ethanol-induced apoptosis and oxidative stress in hepatocytes.
AB  - This short review focuses on ethanol-induced oxidative stress and hepatocyte
      apoptosis. Apoptosis is increasingly recognized as a fundamental biological
      process that impacts on an early development, maturation, and acquisition of
      disease states of multicellular organisms. Although the occurrence of apoptosis
      has been identified for many decades, relatively recent acceptance of this
      principle is evidenced by remarkable increases in special conferences and
      presentations on this topic as well as its rapidly expanding volume of scientific
      literature. Oxidative stress is well recognized to be a key step in the
      pathogenesis of ethanol-associated liver injury. Ethanol administration induces
      an increase in lipid peroxidation either by enhancing the production of oxygen
      reactive species and/or by decreasing the level of endogenous antioxidants.
      Studies in our laboratory using a confocal laser scanning microscopic system
      strongly suggest that agents which inhibit ethanol-induced oxidative stress
      effectively attenuate hepatocyte death, i.e., apoptosis and necrosis. In
      addition, our investigations demonstrated that inhibitors of intracellular
      antioxidants exaggerate ethanol-associated hepatocyte apoptosis. Although the
      detailed mechanism still remains unknown, it is conceivable that an oxidant
      dependent mechanism is largely involved in the process for ethanol-induced
      hepatocyte apoptosis.

PMID- 8986235
TI  - Ethanol-induced leukocyte adherence and albumin leakage in rat mesenteric
      venules: role of CD18/intercellular adhesion molecule-1.
AB  - The adherence and emigration of leukocytes have been implicated as a rate
      limiting step in the microvascular disturbance in a variety of pathogenic events.
      The objective of the present study was to investigate leukocyte-endothelial cell
      adhesion and endothelial barrier function in rat mesenteric microvessels exposed
      to ethanol, which is known to cause inflammation and injury in various organs.
      Mesentery of male Wistar rats was used for intravital microscopic observations.
      Leukocyte adherence and albumin leakage were monitored in single postcapillary
      venules using the intravital fluorescence microscope. Superfusion of 50 mM
      ethanol elicited the leukocyte adherence and albumin leakage within 60 min.
      Pretreatment with a monoclonal antibody directed against either CD18 or
      intercellular adhesion molecule-1 (ICAM-1) significantly prevented the ethanol
      induced increase in leukocyte adherence and decrease in barrier function of
      endothelium. These results suggest that ethanol-induced leukocyte adherence is
      mediated by CD18 on leukocytes and ICAM-1 on endothelial cells. The present study
      further supports that CD18/ ICAM-1-dependent leukocyte-endothelial adhesive
      interactions lead to macromolecular leakage in the postcapillary venules exposed
      to ethanol.

PMID- 8986236
TI  - Chronic ethanol consumption enhances endotoxin induced hepatic sinusoidal
      leukocyte adhesion.
AB  - In alcoholic liver disease, endotoxin has been postulated to play an important
      role in its pathogenesis. Endotoxin is known to lead to impediment of hepatic
      microcirculation, including the adhesion of leukocytes to sinusoidal endothelial
      cells. In this study, the effect of chronic ethanol consumption on the leukocyte
      adhesion elicited by endotoxin was examined. Male Wistar rats were pair-fed with
      a liquid diet containing ethanol or an isocaloric control diet for 6 weeks. The
      liver of anesthetized rats were placed on the nonfluorescent cover-glass for
      observation by an intravital inverted microscope equipped with a silicon
      intensified target camera. The red blood cell (RBC) velocity in hepatic sinusoids
      was measured by an off-line temporal correlation velocimeter (Capiflow, Sweden)
      after intravenous injection of fluorescein isothiocyanate-labeled rat RBC. RBC
      velocity in sinusoids was more severely disturbed in ethanol fed rats than in
      controls. Leukocytes were stained by the intravenous injection of
      carboxyfluorescein succinimidyl ester for a fluorographic observation of
      leukocyte adhesion. After lipopolysaccharide injection, the number of adherent
      leukocytes was significantly greater in ethanol-fed rats than in controls. Plasma
      tumor necrosis factor-alpha levels were also higher in ethanol-fed rats than in
      controls. These results suggest that chronic ethanol consumption aggravates
      endotoxin induced leukocytes adhesion that may result in hepatic microcirculatory
      disturbances. Leukocyte adhesion to the sinusoidal wall may be associated with
      increased in tumor necrosis factor-alpha levels.

PMID- 8986238
TI  - Effect of chronic alcohol intake on energy metabolism in human muscle.
AB  - We investigated the effect of alcohol on muscle energy metabolism by using 31P
      magnetic resonance spectroscopy in 12 chronic alcoholics [6 with neurological
      signs and symptoms (such as cerebellar ataxia or diplopia) and 6 without
      neurological signs or symptoms], compared with five healthy subjects who also
      received acute alcohol loading. Intracellular pH and phosphocreatine (PCr) index
      [PCr/ (PCr + Pi)] were measured during rest, exercise, and recovery in the left
      flexor digitorum superficialis muscle. In healthy subjects, acute alcohol loading
      did not influence the changes of muscle pH and PCr index. Alcoholics with
      neurological signs showed marked decreases in muscle intracellular pH and PCr
      index during exercise and a marked delay of pH recovery after exercise. There was
      no delay of PCr index recovery. Alcoholics without neurological signs showed
      slight decreases in intracellular pH and PCr index, but rapid recovery of both
      intracellular pH and PCr index was observed. Marked decrease and delayed recovery
      in pH, but rapid recovery of PCr index, indicate that the muscle of patients with
      neurological signs produced lactate during and after exercise to maintain the ATP
      level, which implies that anaerobic metabolism is favored over aerobic metabolism
      in these patients.

PMID- 8986237
TI  - Protective mechanism of high-density lipoprotein against endotoxemia in chronic
      alcohol ingestion.
AB  - In the present study, we evaluated the role of high-density lipoprotein (HDL) as
      an endotoxin-binding protein in chronically alcohol-fed rats. Although the blood
      endotoxin level was significantly elevated in chronic ethanol-loaded rats,
      compared with control rats, serum tumor necrosis factor (TNF), ALT, and lactate
      dehydrogenase were not elevated. Serum HDL and its endotoxin-binding capacity
      were significantly increased in chronic ethanol-loaded rats. When Kupffer cells
      isolated from control and chronic ethanol-loaded rats were cultured in the medium
      containing 3 to 30 mg/dl HDL and endotoxin (500 ng/ml), endotoxin uptake and TNF
      production of Kupffer cells were decreased in proportion to the concentration of
      HDL in the medium. These results suggest that the increase in endotoxin-binding
      capacity of HDL may serve as a protective mechanism against endotoxin in chronic
      ethanol-loaded rats.

PMID- 8986239
TI  - Microheterogeneity with concanavalin A affinity of serum transferrin in patients
      with alcoholic liver disease.
AB  - Microheterogeneity of transferrin (Tf) with concanavalin A (ConA) affinity was
      investigated by sensitive lectin-affinity electrophoresis and antibody-affinity
      blotting technique of sera obtained from patients with alcoholic liver disease
      (ALD) and normal subjects. Serum Tf was separated by ConA into three bands-a
      strongly ConA-reactive major band (C1), a weakly reactive minor band (C2), and a
      non-reactive trace band (C3). The C3 fraction was significantly increased in
      patients with ALD before alcohol abstinence, compared with normal subjects and
      patients with ALD after 4 weeks of abstinence. Furthermore, a significant
      correlation was found between the C3 fraction and serum carbohydrate-deficient
      transferrin or gamma-glutamyl-transpeptidase. These results indicate that the
      microheterogeneity of serum Tf in patients with ALD may be a more complex
      abnormality of elongation and processing on the glycans than merely a loss of
      terminal sialic acids. Determination of the C3 fraction is a useful marker for
      ALD.

PMID- 8986240
TI  - Correlation between intrasinusoidal neutrophilic infiltration and ceroid
      lipofuscinosis in alcoholic liver fibrosis with or without fatty change:
      clinicopathological comparison with nutritional fatty liver.
AB  - A histopathological study was conducted on alcoholic liver fibrosis with fatty
      change (21 cases) and alcoholic liver fibrosis without fatty change (18 cases) in
      comparison with nutritional fatty liver (27 cases). The diagnoses of alcoholic
      liver fibrosis groups were clinically fulfilled according to the criteria
      established by the Alcohol and Liver Research Group (Chief: Professor Takeuchi)
      of the Ministry of Education of Japan. Histological diagnosis of alcoholic liver
      fibrosis with fatty change was based on moderate and/or greater fatty
      metamorphosis of the hepatic lobules, alcoholic liver fibrosis without fatty
      change on a lesser degree of fatty metamorphosis than alcoholic liver fibrosis
      with fatty change, and nutritional fatty liver on clinicopathological features.
      All 66 cases were negative for viral markers of hepatitis B surface antigen and
      anti-hepatitis C virus in serum. Intrasinusoidal neutrophil infiltrations were
      significant in cases of alcoholic liver fibrosis groups more often than in cases
      of nutritional fatty liver. The degree of intrasinusoidal neutrophil infiltration
      in cases of alcoholic liver fibrosis groups was higher in cases who had last
      consumed alcohol recently, compared with those with longer abstinence. In
      alcoholic liver fibrosis with fatty change and nutritional fatty liver groups,
      mild-to-moderate degrees of ceroid-lipofuscinosis were recognized, but both fatty
      change and ceroid-lipofuscinosis were decreased according to the deterioration of
      fibrotic changes in alcoholic liver fibrosis with fatty change cases. On the
      other hand, it is significant that the frequency of ceroid-lipofuscinosis in
      alcoholic liver fibrosis without the fatty change group was lower than those of
      the alcoholic liver fibrosis with fatty change and nutritional fatty liver
      groups. Distribution of ceroid-lipofuscinosis has a tendency to be recognized
      around the central zone (zone III) of alcoholic liver fibrosis with fatty change
      cases with mild fibrosis, as in nutritional fatty liver cases, and the ceroid
      lipofuscinosis disperses with the progression of fibrosis. These results suggest
      that fibrosis and fatty droplet deposition lead to microvascular heterogeneity.
      Therefore, the degree and distribution of fatty droplets, ceroid-lipofuscinosis,
      and intrasinusoidal neutrophil infiltration differ, depending on the etiology of
      fatty liver, and are an important histopathological barometer in cases of
      alcoholic liver fibrosis with fatty change and alcoholic liver fibrosis without
      fatty change, thus indicating the degree of fibrosis and the period since last
      alcohol intake.

PMID- 8986241
TI  - Effect of alcohol intake on the efficacy of interferon therapy in patients with
      chronic hepatitis C as evaluated by multivariate logistic regression analysis.
AB  - The effect of alcohol intake on the efficacy of interferon (IFN) therapy was
      evaluated retrospectively in patients with chronic hepatitis C diagnosed by liver
      histology and positive serum hepatitis C virus (HCV)-RNA. Patients included 119
      given IFN therapy and 11 no IFN therapy. Serum HCV-RNA was measured 6 months
      after discontinuation of IFN therapy in 92 treated patients, 27.2% of whom showed
      disappearance of serum HCV-RNA. Multivariate logistic regression analysis
      revealed that this disappearance was affected by alcohol intake, the presence of
      its history (p < 0.05) or cumulative alcohol consumption (kg) (p < 0.01), and
      serum HCV-RNA levels (p < 0.001). The odds ratio associated with serum HCV-RNA
      still positive at 6 months was 7.018 (95% confidence interval: 1.444-34.062) and
      1.004 (1.001-1.007) for the presence of alcohol intake history and the cumulative
      alcohol consumption, respectively. Other predictor variables-such as sex and age
      of patients, history of blood transfusion, HCV genotype, histological findings of
      the liver, and types of IFN-had no influence on the efficacy of the therapy.
      Cumulative alcohol consumption showed a negative correlation with serum HCV-RNA
      levels pretreatment, when the outcome variable was divided into two categories
      based on serum HCV-RNA levels: 10(6) copy/ml or less and 10(7) copy/ml or more.
      Alcohol intake was positively correlated with histological extent of alcoholic
      fibrosis, but affected neither grading nor staging of chronic viral hepatitis. We
      conclude that alcohol intake was a risk factor on the efficacy of IFN therapy in
      chronic hepatitis C patients. This effect was independent of serum HCV-RNA levels
      and histological findings specific for viral hepatitis in the liver.

PMID- 8986242
TI  - Hepatocellular carcinoma associated with alcoholic liver disease: a
      clinicopathological study and genetic polymorphism of aldehyde dehydrogenase 2.
AB  - In this paper, we describe a clinicopathological study of primary hepatocellular
      carcinoma (HCC) associated with alcoholic liver disease without hepatitis virus
      infection. In 180 HCC patients who were admitted to Asahikawa Medical College
      Hospital from 1987 to 1995, 10 patients (6%) had HCC associated with pure
      alcoholic liver disease (Al-HCC), whereas the HCC in 165 patients was associated
      with chronic viral liver diseases, in 2 with primary biliary cirrhosis, in 1 each
      with coexistence of the hepatitis C virus infection and hemochromatosis, and in 2
      with cirrhosis of unknown origin. In the Al-HCC group, all patients were male.
      The diagnosis of HCC was obtained at the age of 54 to 67 years old, and the
      duration of ethanol intake was 33 to 40 years. Four cases had a history of
      temperance. As an underlying liver disease, liver fibrosis was found in three
      cases and liver cirrhosis in seven cases. HCC was diagnosed histologically in all
      cases. Serum alpha-fetoprotein and PIVKA-II were positive in patients with
      advanced HCC. In cases with small HCC, the tumor was resected surgically in three
      cases and percutaneous ethanol injection was performed in two cases. In four
      cases with small HCC, the patients were alive without tumor recurrence during the
      observation period. In advanced HCC, transcatheter arterial chemolipiodolization
      was performed. In the analysis of genetic polymorphism of ALDH 2, all Al-HCC had
      ALDH 2(1)/2(1).

PMID- 8986243
TI  - Prognostic factors for short-term survival in alcoholic hepatitis in Japan:
      analysis by logistic regression.
AB  - Prognostic factors for the outcome of patients with alcoholic hepatitis were
      identified by logistic regression analysis. To predict the outcome immediately
      after admission, clinical data from 97 patients with alcoholic hepatitis on
      admission were introduced to multivariate analysis. Independent prognostic
      factors for favorable outcome were hepaplastin time, peripheral white blood cell
      count, age (40 to 60 years), and serum creatinine level (below 1.4 mg/dl).
      Sensitivity, specificity, positive predictive value, negative predictive value,
      and predictive accuracy were 0.78, 0.89, 0.78, 0.89, and 0.86, respectively. The
      resultant equation for the death rate was applied to another set of patients with
      alcoholic hepatitis as a validation study. Predictive accuracy estimated 0.95 in
      validation. The prognostic index derived was simple, accurate, and useful in the
      prediction of the outcome in patients with alcoholic hepatitis. Furthermore, it
      provides the clinician with an indication of the necessity for the intensive care
      of patients in a critical condition.

PMID- 8986244
TI  - Two survival cases of alcoholic lactic acidosis complicated with diabetes
      mellitus and alcoholic liver disease.
AB  - We have experienced two patients with alcoholic lactic acidosis complicated with
      liver disease and diabetes mellitus who were successfully treated. They developed
      hypoglycemia, dehydration, lactic acidosis, and renal failure after drinking a
      large volume of alcohol without eating for 1 week before onset. Acidosis was
      thought to be directly related to excessive alcoholic intake, because it was no
      associated with severe liver failure and rhabdomyolysis. During monitoring of
      respiratory and circulatory functions, a rapid infusion of fluids adjusting to
      water and electrolyte imbalance was performed. A mixture of physiological saline
      and 5% glucose solution was thought to be effective in these cases. Patients
      recovered from renal failure and lactic acidosis without hemodialysis. Our
      experience will hopefully provide a key to successful treatment of fatal
      alcoholic lactic acidosis.

PMID- 8986245
TI  - Soluble ICAM-1 and VCAM-1 serum levels in uveitis.
AB  - Serum level of soluble forms of adhesion molecules ICAM-1 and VCAM-1 has been
      evaluated in a group of patients presenting different clinical forms of uveitis.
      An increase in serum level of ICAM-1 has been found but not of VCAM-1. Serum
      level of VCAM-1 can be an useful marker of ocular inflammation in the evaluation
      of uveitis.

PMID- 8986246
TI  - The efficacy of E.P.D., a new immunotherapy, in the treatment of allergic
      diseases in children.
AB  - A double blind study was made on a group of 35 children, 8 of whom were allergic
      to Grass and 27 allergic to Pteronyssinus and Farinae Dermatophagoides. We
      verified the efficacy and tolerability of a new immunotherapy called E.P.D.
      (Enzyme Potentiated Desensitization). This particular immunotherapy consists in
      an intradermal injection of a mix made up of an allergic solution at extremely
      low doses and an enzyme, beta-glucuronidase. The vaccine is administered once a
      year, two weeks before pollen peaks for children with seasonal allergies and two
      times a year, in February and November, for children with non-seasonal allergies
      (Dermatophagoides). The results, statistically analyzed on the basis of a
      symptoms score, showed good clinical efficacy in patients affected by both
      seasonal and non-seasonal allergies. Due to the clinical effectiveness, easy
      administration and excellent tolerability of the immunotherapy, E.P.D. is
      particularly suited for treating or reducing allergic symptoms in allergic
      children.

PMID- 8986247
TI  - Occupational health surveillance: contributions from the National Health
      Interview Survey.

PMID- 8986248
TI  - Comparison of single photon emission computed tomography findings in cases of
      healthy adults and solvent-exposed adults.
AB  - Single photon emission computed tomography (SPECT) is a useful tool in measuring
      dynamic brain functioning. Its potential to reveal the physiological mechanisms
      of neurotoxicity has not been fully explored. In the present study, the SPECT
      findings for 25 healthy control subjects were compared to the findings for 25
      mixed organic solvent exposure subjects. Specific physiological abnormalities
      related to regional cerebral blood flow activity (rCBF) were revealed. In the
      early phase of uptake, significantly decreased uptake was found in the mixed
      organic solvent group; in the late phase of uptake, a significant increase in
      uptake was found in specific regions of interest. The discovery of this
      abnormality in brain functioning may be a significant step toward the creation of
      a biological marker of neurotoxicity. Early detection of neurotoxicity is
      important in occupational medicine to prevent neurotoxic illnesses in working
      populations.

PMID- 8986249
TI  - Occupational risks for the development of brain tumors.
AB  - Occupationally related risk factors were assessed in a population-based, case
      control study of 139 patients with primary brain tumors (BT), carried out in
      central Israel between 1987-1991. For each case, two control groups were matched
      by age (+/-5 years), sex, and ethnic origin. The interview schedule included
      questions about lifelong occupational history before diagnosis. Odds ratios (OR)
      for BT, according to industrial categories, showed a significantly increased risk
      among blue-collar workers, especially among those employed in the textile
      industry, and among drivers and motor vehicle operators. When histologic tumor
      types were assessed separately, a significantly increased risk for malignant BT
      was found among drivers and motor vehicle operator occupations, while for
      meningiomas, an increased risk was found among weavers and tailors. Our results
      may provide clues for etiology and prevention measures.

PMID- 8986250
TI  - A case-control study of hematopoietic and lymphoid neoplasms: the role of work in
      the chemical industry.
AB  - The present case-control study was conducted in an effort to determine if work in
      the chemical industry is related to excesses of certain hematopoietic and
      lymphoid neoplasms. Cases who died from non-Hodgkin's lymphoma, multiple myeloma,
      and leukemia were matched by race, gender, age, year of death, and county of
      residence to controls who died from cardiovascular disease. A total of 618 (309
      matched pairs) white male residents of Kanawha County, WV, aged 23-96, who had
      died between 1965 and 1990 were identified. Conditional logistic regression was
      conducted and yielded an association between chemical industry work and death due
      to non-Hodgkin's lymphoma, multiple myeloma, and lymphoid leukemia among subjects
      who died at age < 65. These results are consistent with the findings of previous
      studies linking work in chemical manufacturing to hematopoietic and lymphoid
      neoplasms, and indicate that the excesses may be related to the occupational
      exposures in men who died at younger ages.

PMID- 8986251
TI  - Case-control study of cancer risk in tetraethyl lead manufacturing.
AB  - A case-control study was conducted to investigate the relative risk of cancer
      detection among Du Pont employees who worked in a tetraethyl lead (TEL)
      manufacturing area. The study's objective was to determine whether the employees'
      risk of developing or dying from cancer was associated with occupational exposure
      to TEL. All malignant neoplasms detected in the active and pensioned employee
      population during the period 1956-1987 were studied. TEL exposure was estimated
      by the following measures: ever employed in the TEL area, years of employment in
      TEL, TEL exposure rank, and the TEL cumulative exposure index. TEL manufacturing
      exposed employees to both organic and inorganic lead compounds. Because the
      underlying data did not permit the exposure assessment to distinguish between
      organic and inorganic lead, the TEL exposure measures reflect exposure to the TEL
      manufacturing process itself. The effects of latency, cigarette smoking habits,
      and exposures to other known or suspected carcinogens at the plant were also
      assessed. A strong association was observed between exposure to the TEL
      manufacturing process and rectal cancer (the odds ratio was 3.7 with 90%
      confidence limits of 1.3-10.2 for the analysis of ever/never exposed to TEL). An
      exposure-response relationship was noted with a fourfold elevation in the odds
      ratio at the high-very high cumulative exposure level. These patterns were even
      more pronounced after assuming a 10 year latency. Similar results were obtained
      for cancers of the sigmoid colon. These findings suggest that exposure to the TEL
      manufacturing process may have played a causal role in the colorectal cancer
      experience at the plant. This position is supported by the graded exposure
      response relationships, the consistency of the results across exposure measures,
      the specificity of the health outcome (i.e., colorectal cancer), and the strength
      of the association. However, the evidence for causality is not compelling. This
      is the first report of an association between TEL manufacturing and colorectal
      cancer, and the evidence is compatible with a wide range of causal (i.e.,
      indirect vs. direct acting; initiating vs. promoting) and noncausal (i.e.,
      statistical and methodological bias; coincidence) interpretations.

PMID- 8986252
TI  - Comparability of different methods of retrospective exposure assessment of metals
      in manufacturing industries.
AB  - Many occupational case-control studies have relied on either self-report or
      exposure assessment based on job titles linked to a job exposure matrix (JEM) as
      opposed to the generally considered more accurate, but labor intensive, method of
      expert review of job histories. Our study examined the comparability of these
      different methods in assessing occupational exposure to the metals copper (Cu),
      lead (Pb), and iron (Fe) in manufacturing industries. Subjects were older people
      from a case-control study of a neurologic disease, and consisted of 188
      individuals (72% male, 85% white) who had worked an average of 22.4 years in the
      manufacturing industry. An industrial hygienist review (IHR) of occupational
      history data from a comprehensive questionnaire was used as the reference method.
      The percent agreement (%A), sensitivity (SE), and specificity (SP) for direct
      self-report of metal exposures were: Cu, %A = 94.6, SE = 83.6, SP = 96.1; Pb, %A
      = 91.9, SE = 72.5, SP = 93.5; and Fe, %A = 82.7, SE = 64.5, SP = 88.1. Using the
      National Institute for Occupational Safety and Health (NIOSH) JEM, we analyzed
      the jobs of 115 of the 188 study subjects who had all their jobs listed in the
      JEM. Exposure assessment based on the NIOSH JEM compared with the IHR resulted in
      greater misclassification relative to direct self-report: Cu, %A = 81.5, SE =
      21.2, SP = 89.2; Pb, %A = 86.0, SE = 0.0, SP = 92.6; and Fe, %A = 69.2, SE =
      15.5, SP = 86.4. For all three study metals, combining the information from both
      direct self-report and the JEM did not improve upon the results compared with
      direct self-report alone. Due to the complex nature of metal exposure assessment,
      we suggest using an expert review of job histories whenever possible to minimize
      potential misclassification.

PMID- 8986253
TI  - Triple primary cancers involving kidney, urinary bladder, and liver in a dye
      worker.
AB  - A case of triple primary cancers (renal cell carcinoma of the kidney,
      transitional cell carcinoma of the bladder, and hepatocellular carcinoma of the
      liver) was reported at autopsy. A 53-year-old man, who had a history of exposure
      to benzidine, underwent nephrectomy for a left renal cell carcinoma and 10 years
      later, transurethral resection of bladder tumor (TUR-Bt) for a transitional cell
      carcinoma of the bladder. At the age of 65, he was diagnosed as having multiple
      hepatic tumors. Histological examination of biopsy specimens showed these lesions
      to be undifferentiated carcinomas. Immunohistological examination of both biopsy
      and autopsy specimens revealed that multiple hepatic tumors were hepatocellular
      carcinomas, not metastatic tumors from kidney or urinary bladder: tumor cells of
      hepatic tumors were positive for alpha-fetoprotein, although renal cell
      carcinomas and transitional cell carcinomas of urinary bladder were positive for
      Ber-EP4 and keratin, respectively. These findings suggest not only that
      immunohistological examination is helpful for the diagnosis of multiple primary
      cancers but also that benzidine may be hepatocarcinogenic in addition to those
      cancers that are known to be associated with benzidine exposure, i.e., renal cell
      carcinomas and transitional cell carcinomas in urinary bladder.

PMID- 8986254
TI  - Respiratory function in shoe manufacturing workers.
AB  - A study of respiratory findings was performed on 376 female workers employed in a
      shoe manufacturing plant. The mean age of the workers was 32 years and the mean
      duration of their employment was 12 years. These workers were predominantly
      nonsmokers. Acute and chronic respiratory symptoms were recorded for each worker,
      and lung function was measured before and after the work shift. Maximum
      expiratory flow-volume (MEFV) curves were performed on which forced vital
      capacity (FVC), 1-second forced expiratory volume (FEV1), and flow rates at 50%
      and the last 25% (FEF50, FEF25) were measured. Significantly higher prevalences
      of all chronic respiratory symptoms were recorded in exposed compared to control
      workers; in particular, chest tightness (exposed: 44.7%; control: 0%), dyspnea
      (exposed: 42.6%; control: 2.0%), and rhinitis (exposed: 46.3%; control: 2.4%)
      were far more prevalent in workers than in controls. Among the shoe workers,
      there was also a high prevalence of acute symptoms that developed during the work
      shift, being most pronounced for nose and throat irritation (61.4%). The
      prevalence of acute and chronic respiratory symptoms increased with duration of
      employment. Statistically significant across-shift reductions were recorded for
      all ventilatory capacity tests for the group as a whole. In comparison to
      predicted, the measured ventilatory capacity parameters were significantly lower
      for all workers (p < 0.01). Lung function abnormalities increased with duration
      of employment. Environmental measurements demonstrated that benzene, fur, and
      synthetic fibers were found at higher than allowable maximal concentrations
      (Croatian standards). The data suggest that work in the shoe manufacturing
      industry may be responsible for the development of acute and chronic respiratory
      impairment.

PMID- 8986255
TI  - Epidemic of asthma in a wood products plant using methylene diphenyl
      diisocyanate.
AB  - Eighteen employees with lower respiratory symptoms later confirmed to be
      occupational asthma were referred for evaluation. All were employees of a single
      wood products plant using heated methylene diphenyl diisocyanate (MDI) in the
      manufacture of a synthetic wood product. Of the 18, 15 had no prior airway
      symptoms or other known bronchial injury, and 16 had positive methacholine
      bronchial provocation tests. All cases occurred during a 2.5-year period after
      exposure to a new manufacturing process using steam-heated MDI resin in a new
      manufacturing facility. Initially, employees developed symptoms related to the
      start-up process in the plant, with possible higher MDI exposures and probable
      higher resin temperatures. Later, most employees who developed new symptoms
      worked in areas of the plant where they were exposed mostly to heated boards.
      This suggests MDI sensitization arising at lower temperatures than previously
      considered likely for this substance.

PMID- 8986256
TI  - Designing prevention-oriented software for workplace health and safety.
AB  - Rapid changes in technology and health services organization are propelling
      information-driven decision making in all aspects of business. The potential of
      electronic data processing to reduce costs and increase efficiency has been
      heralded, but disease and injury prevention have received scant attention.
      Prevention-oriented software for surveillance and disability management must
      generate population- and case-level measures of magnitude and severity of
      occupational injury and illness. A public domain program, called WIZARD, was
      developed as a model. With 12 data elements, it generates, from injury and
      employment files, injury- and return-to-work rates, avoidable costs, attributable
      cases using several reference rates, and case lists from screening criteria. In
      conjunction with an explicit case definition, screening criteria for case follow
      up, and guidelines for medical, disability, and health and safety management,
      software can play a significant role in prevention.

PMID- 8986257
TI  - Risks of developing noise-induced hearing loss in employees of urban music clubs.
AB  - Noise-induced hearing loss has previously been reported among rock musicians.
      This study sought to determine whether a hazard of noise-induced hearing loss
      exists for music club employees other than musicians themselves. Sound levels at
      eight live-music clubs were measured and symptoms of noise exposure in 31 music
      club employees were assessed by questionnaire. The average sound level at the
      various clubs during performances ranged from 94.9 to 106.7 dBA. The overall
      sound level average, including both performance and ambient levels, ranged from
      91.9 to 99.8 dBA. Symptoms of noise exposure, such as tinnitus and subjective
      hearing loss, correlated with sound intensity. Only 16% reported regular use of
      hearing protection. We conclude that employees of music clubs are at substantial
      risk of developing Noise-Induced Hearing Loss, due to chronic noise exposure
      which consistently exceeded safe levels. Hearing protection is used much too
      infrequently. The development of hearing conservation programs for this large
      group of workers is essential.

PMID- 8986258
TI  - Ten-year follow-up study on the relation between the development of non-insulin
      dependent diabetes mellitus and occupation.
AB  - To investigate the relation between occupation and the development of non-insulin
      dependent diabetes mellitus (NIDDM), we undertook a 10-year follow-up survey of
      male employees of a zipper and aluminum sash factory in Japan. Of 1,218 employees
      we followed 1,087 subjects. We classified the subjects into five occupations:
      managers, technical workers, clerical workers, workers in transport, and
      laborers. NIDDM incidence was 3.1% for 10 years. The age-adjusted incidence of
      the workers in transport was the highest and that in laborers was the lowest. We
      used a multiple logistic analysis for adjustment with baseline characteristics
      such as age, BMI, fasting plasma glucose, and family history of diabetes
      mellitus. Adjusted relative risk of the workers in transport compared with the
      laborers was significantly high (3.95). Our work suggests that occupation is
      related to the development of NIDDM.

PMID- 8986259
TI  - Predictors of return to work following carpal tunnel release.
AB  - Little is known about factors that predict return to work following carpal tunnel
      release. Patients enrolled in a prospective, community-based study of carpal
      tunnel syndrome in Maine were evaluated with standardized questionnaires
      preoperatively and 6 months following carpal tunnel release. Univariate and
      multivariate analyses were performed to identify baseline factors associated with
      work disability 6 months following surgery. Thirty-one of 135 patients (23%) were
      out of work because of CTS 6 months following surgery. The predominant
      preoperative variables associated with work absence due to CTS 6 months
      postoperatively in logistic regression analyses were Workers' Compensation, work
      absence preoperatively, and worse mental health status (p < or = 0.01 for each).
      In analyses that considered postoperative as well as preoperative variables,
      persistence of symptoms following surgery was the most striking predictor of
      failure to return to work due to CTS (p < 0.0001). Preoperative correlates of
      less complete relief of symptoms in multivariate models included involvement of
      an attorney, milder preoperative symptom severity, preoperative work absence (p <
      0.005 for each) and exposure to hand intensive work (p = 0.04). These data
      indicate that economic and psychosocial variables have a strong influence upon
      both return to work and the extent of symptom relief 6 months following surgery
      for carpal tunnel syndrome.

PMID- 8986260
TI  - Injuries due to assaults on psychiatric hospital employees in Washington State.
AB  - In order to estimate rates and identify risk factors for assaults on employees of
      a state psychiatric hospital, we examined workers' compensation claims, hospital
      recorded incident reports, and data collected in a survey of ward staff. Results
      revealed 13.8 workers' compensation claims due to assault per 100 employees per
      year. Assaults were responsible for 60% of total claims. Incident reports
      revealed 35 injuries due to assault per 100 employees per year. Survey data
      revealed 415 injuries due to assault per 100 employees per year. Of the
      respondents, 73% reported at least a minor injury during the past year. Assault
      management training in the past year was associated with less severe injuries.
      Working in isolation, the occupation of mental health technician, and working on
      the geriatric-medical hospital unit were associated with more severe injuries
      during the past year. Assaults on staff in psychiatric hospitals represent a
      significant and underrecognized occupational hazard.

PMID- 8986261
TI  - Hospital records: an underutilized source of information regarding occupational
      diseases and exposures.
AB  - A 1993 study examined the association between pneumoconiosis and cor pulmonale
      using a computerized data base of hospital records in Ontario (Hospital Medical
      Records Institute, HMRI). The present investigation was undertaken to confirm the
      coding of the diagnoses of a subset of the hospital discharges from that study,
      to determine the validity of the coding of the diagnoses of coal workers'
      pneumoconiosis (CWP), and to identify work exposure (occupation and industry)
      information available in hospital records. We sent abstraction forms to hospitals
      for 521 subjects who were hospitalized for pneumoconiosis, cor pulmonale, or both
      conditions, requesting information regarding diagnoses, occupation and industry
      data, and X-ray results. Abstracts were received for 720 (76%) of 944 discharges
      that were sought. The hospital abstractions confirmed the HMRI coding for 90% of
      the charts with these conditions, including 63%, 97%, and 96% discharges for CWP,
      silicosis, and asbestosis, respectively. Specific dust exposures were indicated
      in 42% of the charts with a code indicating a diagnosis of CWP, and of these, 67%
      indicated exposure to coal dust. Of charts with a code indicating a diagnosis of
      silicosis, 73% with specific dust information indicated silica exposure, and 95%
      of those for asbestosis indicated exposure to asbestos. Of 34 individuals in this
      data set known from the Ministry of Labour's Chest Clinic X-ray Surveillance
      Program of miners to have silicosis, 33 (97%) were diagnosed by the hospitals as
      having pneumoconiosis, and all but two were silicosis. Hospital records, as
      reflected by HMRI data, are reliable indicators of cor pulmonale and
      pneumoconiosis. The agreement with the Chest Clinic's X-ray diagnoses provides
      additional objective confirmation of the accuracy of the hospital information.
      There were relatively few cases of silicosis miscoded as CWP. At least for
      pneumoconioses, hospital records contained information about the exposures that
      led to these diseases in approximately 50% of the cases. However, whether
      hospital records would prove useful for detecting other work-related conditions
      that are not pathognomonic of occupation is not known. The importance of taking
      occupational histories needs continued emphasis in medical education and
      training.

PMID- 8986262
TI  - Manganese in the U.S. gasoline supply.
AB  - Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese
      compound recently approved for use in the United States as a gasoline additive.
      MMT use is expected to increase. This Commentary analyzes the impact of MMT use
      on population exposure to manganese, the health effects associated with manganese
      exposure, and the possibility that MMT use will lead to toxicity in the
      population. Although MMT use would result in only a small increment in most
      people's manganese exposure, certain populations will be disproportionately
      exposed. Although manganese is an essential nutrient at low levels, high-level
      manganese exposure leads to a characteristic severe nervous system toxicity.
      Pulmonary toxicity also occurs at high levels of exposure, and developmental
      toxicity to fetuses is an important concern based on more limited data. Selected
      subpopulations may be especially susceptible to the toxic effects of manganese.
      The critical question is whether the additional population exposure to manganese
      that would result from widespread MMT use would lead to toxic effects. Currently
      available evidence does not permit firm conclusions. Common sense and prudence
      therefore dictate that MMT not be used until further data are available and its
      safety is confirmed. Several measures are recommended to address the impending
      use of MMT in the U.S. gasoline supply.

PMID- 8986263
TI  - Dose-response relations between urinary cadmium and tubular proteinuria in adult
      workers .

PMID- 8986264
TI  - Re: Commentary on "dose-response relations between urinary cadmium and tubular
      proteinuria in adult workers".

PMID- 8986265
TI  - Re: Mortality of workers at a nuclear materials plant.

PMID- 8986266
TI  - Influence of social class on SMRs among Y-12 workers.

PMID- 8986267
TI  - Association of late onset spastic paraparesis and dementia: probably an autosomal
      dominant form of complicated paraplegia.
AB  - The hereditary paraplegias are a heterogeneous group of genetic disorders
      characterized mainly by spastic paraparesis, which may be found as an isolated
      "pure form" known as Strumpell-Lorrain syndrome, or associated with a wide group
      of other manifestations [Harding, 1990; McKusick, 1994]. We studied two unrelated
      families, one with five members and the other with 11 members (over four
      generations), affected by a syndrome of late onset spastic paraparesis and
      dementia. Both pedigrees suggest an autosomal dominant pattern of inheritance.
      However, this cannot be concluded definitely because male-to-male transmission
      was not seen. Since this disorder has a late age of onset, we still do not know
      who will become affected in the second, third, and fourth generations. The
      association of late onset spastic paraparesis and dementia, without other
      pathological findings, has not been reported and probably represents a distinct
      entity.

PMID- 8986268
TI  - XY gonadal dysgenesis associated with a multiple pterygium syndrome phenotype.
AB  - Most phenotypic females with an XY male karyotype do not have significant
      extragenital anomalies; however, some patients with additional abnormalities have
      been described. We report on an individual with XY gonadal dysgenesis, mental
      retardation, microcephaly, growth retardation, and multiple pterygia. Although
      not previously reported, the possible relationship between these findings is
      discussed in the context of evident heterogeneity of XY gonadal dysgenesis.

PMID- 8986269
TI  - Bronchopulmonary-foregut malformations: a continuum of paracrine hamartomas?
AB  - The bronchopulmonary-foregut malformations (BPFM) are usually sporadic, solitary
      cystic hamartomas involving conducting airways, arteries, venous drainage, and
      lung parenchyma. Transitional, compound hamartomas exist, and only their
      morphology is well-known. Between 1984-1994 we encountered and studied 10
      unrelated patients and a stillborn infant with BPFM (out of 24,000 families). Ten
      were diagnosed in utero and one at birth as having congenital cystic adenomatoid
      malformation of the lung (CCAML). Postnatally, two diagnoses (20%) were corrected
      to bronchogenic cyst (BC) and diaphragmatic hernia, respectively. Bilateral lung
      involvement was present in 1 patient, and in 2 there was a considerable
      macroscopic regression of the hamartoma. Histologic studies of the six resected
      CCAML confirmed the diagnosis and implied dysregulated paracrine growth with its
      cellular and extracellular growth factors, protooncogenes, oncogenes, cytokines,
      cell-adhesive molecules, and receptors of these regulatory peptides, and their
      complex interactions as developmental morphogens in time and space.

PMID- 8986270
TI  - Findings in children exposed in utero to phenytoin and carbamazepine monotherapy:
      independent effects of epilepsy and medications.
AB  - Our objective was to evaluate the patterns of malformations in children exposed
      in utero to phenytoin (DPH) and carbamazepine (CBZ) monotherapy, and to compare
      them prospectively with matched mother-child pairs exposed to nonteratogens, and
      to separate the effects of antiepileptic drugs (AEDs) from those of epilepsy by
      collecting groups of untreated epileptics and those treated with DPH and CBZ for
      conditions other than epilepsy. This was a prospective, controlled, and blinded
      observational study. Thirty-six mother-child pairs exposed to CBZ monotherapy, 34
      pairs exposed to DPH monotherapy, and 9 nonmedicated epileptic women and their
      children were compared with matched mother-child pairs exposed to nonteratogens.
      The control mothers were matched for maternal age, time of consultation,
      obstetric history, and socioeconomic status (SES). One main outcome measures a
      "blinded" morphological assessment of the offspring. We found that minor
      anomalies were significantly more common among children of epileptics on either
      drug (P = 0.01) and among DPH-treated nonepileptic offspring (P = 0.03). Among
      epileptics, the relative risk for minor anomalies following DPH (2.1) was similar
      to that after exposure to either DPH (P = 0.006) or CBZ (P = 0.01). Increased
      rates of hypertelorism were detected among DPH-exposed offspring. High forehead,
      frontal bossing, malar hypoplasia, epicanthus and micrognathia were associated
      with untreated epilepsy, as well as with DPH and CBZ treatment.

PMID- 8986271
TI  - Clinical, morphological, and biochemical phenotype of a new case of Ehlers-Danlos
      syndrome type VIIC.
AB  - Ehlers-Danlos syndrome (EDS) type VIIC is a newly recognized human disorder which
      results from failure to remove the amino-terminal propeptide of type I
      procollagen. Four cases of EDS type VIIC have been reported, and here we describe
      a fifth case. The propositus was a 1,445 g male infant born at 30 weeks of
      gestation following premature rupture of membranes. He had wide fontanelles,
      prominent eyes with swollen eyelids and blue sclerae, anteverted nostrils,
      micrognathia, umbilical hernia, short stubby fingers, and cutis laxa with
      hirsutism. At age 3 months, during the repair of the umbilical hernia, he was
      noted to have unusual skin fragility. Examination of skin by scanning electron
      microscopy showed frayed collagen fibrils, and transmission electron microscopy
      showed the hieroglyphic collagen fibril morphology characteristic of the
      disorder. As reported in other cases, cultured fibroblasts synthesized type I
      procollagen that was very poorly processed at the amino-terminal propeptide
      cleavage site. the 5 known cases of human EDS type VIIC characterize a distinct
      clinical phenotype, making this condition recognizable at birth before
      manifestation of severe skin fragility. The diagnosis can be confirmed by
      biochemical studies of type I procollagen synthesis and by electron microscopic
      examination of skin.

PMID- 8986272
TI  - Molecular cytogenetic identification of four X chromosome duplications.
AB  - Four cases with previously unidentified X-chromosome abnormalities were studied
      by standard cytogenetic techniques and FISH in order to demonstrate the origin of
      the extra segment on the abnormal X chromosomes. All cases were identified as X
      chromosome duplications by using a chromosome-specific painting probe.
      Application of appropriate locus-specific DNA probes as an adjunct to GTG- and
      RBG-banding proved useful in defining the breakpoints and the extent of the
      duplications. Although the duplicated X chromosome in female cases was
      selectively inactivated, as demonstrated by its late-replicating pattern,
      abnormal clinical findings were manifested in 3 female patients.

PMID- 8986273
TI  - Anophthalmia, intracerebral cysts, and cleft lip/palate: expansion of the
      phenotype in oculocerebrocutaneous syndrome?
AB  - We report on a patient with multiple congenital anomalies including anophthalmia,
      cleft lip and palate, and central nervous system anomalies similar to the case
      reported by Leichtman et al. [1994: Am J Med Genet 50:39-41] and to
      oculocerebrocutaneous (Delleman) syndrome. Although the two cases and those with
      oculocerebrocutaneous syndrome may represent separate but overlapping entities,
      our patient and the case described by Leichtman et al. [1994: Am J Med Genet
      50:39-41] may represent a more severe form of oculocerebrocutaneous syndrome.

PMID- 8986274
TI  - Genetic testing for breast cancer susceptibility: awareness and interest among
      women in the general population.
AB  - Previous research has suggested that demand for genetic testing for breast cancer
      susceptibility may be quite high, even among those at relatively low risk of
      carrying a mutation. This study examined the extent to which a group of female
      HMO enrollees were aware of the discovery of the BRCA1 gene and, without having
      received detailed information about the test, whether they would be interested in
      being tested to find out if they have the gene. Factors associated with awareness
      of and interest in testing were also examined. Four hundred seventy-three women
      age 50 and over, almost all of whom did not have an increased risk of breast
      cancer based on family history, were surveyed by telephone. Fifty-one percent of
      respondents had heard about the discovery of a breast cancer gene. In logistic
      regression analysis, women who described themselves as comfortable financially,
      had at least some college education, and were premenopausal were more likely to
      have heard of the gene discovery than women who were not comfortable financially,
      had no more than a high school education, and were postmenopausal. Sixty-nine
      percent of the respondents said that they would be interested in being tested to
      find out if they had a breast cancer gene. Women who were younger than 60, white,
      believed their family would benefit if they had a mammogram, and believed that
      regular mammograms give them a feeling of control over their health, were more
      likely to be interested in testing than those who were 60 or older, African
      American or other, and did not believe that their family would benefit if they
      had a mammogram or that mammograms give them a feeling of control over their
      health. These findings have implications for education and counseling. Women who
      express an interest in being tested must be made fully aware of the limitations
      and possible consequences of testing. Special efforts may be needed to make
      information about testing available to women who have low levels of education.

PMID- 8986275
TI  - Mosaic partial trisomy 17 due to a ring chromosome identified by fluorescence in
      situ hybridisation.
AB  - We report on a 3-year-old-girl with mosaic partial trisomy 17 due to an
      additional ring chromosome 17 in 13% of cells analysed. This was identified by
      fluorescence in situ hybridisation (FISH) using a whole chromosome 17 specific
      paint as well as probes specific for the Smith-Magenis and Miller-Dieker regions
      of chromosome 17p. This girl showed mild developmental delay with subtle facial
      and other minor abnormalities including single palmar creases, generalised joint
      laxity, and a scoliosis.

PMID- 8986276
TI  - Another Arab patient with overlap of Varadi-Papp/Opitz trigonocephaly syndromes?
AB  - We describe a Bedouin boy with multiple congenital anomalies/mental retardation
      (MCA/MR). He has frontal bossing, ridged metopic suture, bilateral ptosis, right
      squint, depressed nasal bridge, small nose, anteverted nostrils, lobulated
      tongue, polydactyly of both hands, microphallus, hypoplastic scrotum,
      microtestes, dysgenesis of corpus callosum, and a Dandy-Walker variant. This
      phenotype overlaps both the Varadi-Papp syndrome (OFD VI) and Opitz
      trigonocephaly (C syndrome). This phenotypic overlap is discussed in light of the
      concept of splitting and lumping in genetic diseases.

PMID- 8986277
TI  - Diagnosis of Fanconi anemia in patients without congenital malformations: an
      international Fanconi Anemia Registry Study.
AB  - Data were analyzed from 419 Fanconi anemia (FA) patients enrolled in the American
      Registry of the International Fanconi Anemia Registry (IFAR) to determine whether
      Fanconi anemia (FA) patients without major congenital malformations (CM) have
      distinguishing characteristics that can lead to an earlier diagnosis. These
      included 377 patients reported by physicians to the IFAR and 42 patients examined
      by us. The number of FA patients in each group without CM was 128 and 16,
      respectively; one third of all patients lacked CM. We found that height, weight,
      and head circumference were < or = 5th centile in 26.6%, 18.0%, and 8.6% of FA
      patients without CM referred to the IFAR, and in 43.8%, 25.0%, and 43.8% of FA
      patients without CM examined by us. Minor anomalies were reported in 9.4% of FA
      patients without CM referred to the IFAR and 100% of FA patients without CM
      examined by us. Most FA patients without CM have alterations in growth
      parameters, skin pigmentation abnormalities, or microphthalmia. Increased
      awareness of the complete spectrum of FA by clinicians will enable an earlier
      diagnosis to be made.

PMID- 8986278
TI  - Carrier testing in the fragile X syndrome: attitudes and opinions of obligate
      carriers.
AB  - This study surveyed obligate carriers of the fragile X syndrome fra(X) to
      ascertain opinions and attitudes regarding carrier testing. Female carriers of
      fra(X) syndrome were recruited during their visits to the Fragile X Clinic at
      Duke University Medical Center. Twenty-eight obligate carriers completed a 48
      question structured interview and a visual analog scale (VAS). Strong trends in
      the responses were identified. Fra(X) syndrome was viewed as a very serious
      problem and the risk to offspring high. Subjects reported that prior knowledge of
      carrier status would have changed their reproductive plans. All felt that
      relatives should be informed about the inheritance of fra(X) syndrome; the mean
      age given for preferred age to inform their children of the inheritance of fra(X)
      syndrome was 12 years, and mean age given for optimal timing of carrier testing
      was 10 years. The women interviewed indicated that growing up with knowledge of
      their carrier status would have been preferable to learning this information as
      adults and they endorsed an aggressive approach to informing and testing their
      children. Further investigation is warranted to determine the psychological
      consequences of carrier testing for fra(X) syndrome in order to develop
      appropriate guidelines for testing and informing individuals at risk for fra(X)
      syndrome.

PMID- 8986279
TI  - Tetramelic mirror-image polydactyly and a de novo balanced translocation between
      2p23.3 and 14q13.
AB  - We report on a male infant with tetramelic mirror-image polydactyly and a de
      novo, balanced reciprocal translocation between 2p23.3 and 14q13. This patient
      suggests that a novel gene, which functions in the morphogenesis of the hands and
      feet along the anterior-posterior axis, may be located at 2p23.3 or 14q13.

PMID- 8986280
TI  - Hirschsprung disease, postaxial polydactyly, and atrial septal defect.
AB  - We report on an infant girl with Hirschsprung disease, postaxial polydactyly, and
      atrial septal defect who was born to a consanguineous Iraqi couple. A similar
      condition of aganglionic megacolon, postaxial polydactyly, and ventricular septal
      defect with a presumed autosomal recessive (AR) inheritance was reported by
      Laurence in two sibs [Laurence et al.; J Med Genet 12: 334-338, 1975].

PMID- 8986281
TI  - A paternally derived inverted duplication of 7q with evidence of a telomeric
      deletion.
AB  - We report on a de novo constitutional rearrangement involving the long arm of
      chromosome 7 in a second trimester fetus with the karyotype of 46,XX, inv dup del
      (7)(pter-q36::q36-q21.2:) pat. Both a large duplication (q21.2-q36) and a small
      deletion (within q36) were confirmed by FISH studies. DNA analysis on the family
      showed that the abnormal chromosome was derived from a single paternal homolog. A
      mechanism is proposed in light of this finding. The phenotype at autopsy was
      consistent with reported cases of similar duplications in chromosome 7 in that
      hydrocephalus, a depressed nasal bridge, low set ears, microretrognathia and a
      short neck were present.

PMID- 8986282
TI  - Lethal multiple pterygium syndrome: suggestion for a consistent pathological
      workup and review of reported cases.
AB  - We report on 2 brothers with lethal multiple pterygium syndrome (LMPS) born to
      non-consanguineous parents as late spontaneous abortions. Both fetuses presented
      with massive nuchal edema, and facial anomalies including cleft palate and broad
      ribs. Apparently, several subgroups of LMPS exist. Differentiation is difficult,
      as there is no consistent agreement on a workup protocol for autopsies. We
      compared the findings in the literature on cases with LMPS, and we suggest a
      standardized workup as an initial step for more efficient differentiation between
      various subgroups.

PMID- 8986284
TI  - Family with branchial arch anomalies, hearing loss, ear and commissural lip pits,
      and rib anomalies. A new autosomal recessive condition: branchio-oto-costal
      syndrome?
AB  - We report on a family in which 3 sibs were affected with conductive deafness,
      bilateral preauricular and commissural lip pits, monolateral branchial fistula,
      and rib anomalies. On the basis of parental consanguinity, lack of clinical
      variability and affected subjects of both sexes, this condition seems to be
      inherited as an autosomal recessive trait. We suggest that these findings
      comprise a new autosomal recessive entity of branchial, auricular and costal
      anomalies, for which we suggest the acronym BOC (branchio-oto-costal) syndrome.

PMID- 8986283
TI  - VACTERL with hydrocephalus in twins due to Fanconi anemia (FA): mutation in the
      FAC gene.
AB  - We present a dizygotic twin pair each with ventriculomegaly, a radial ray defect
      and multiple malformations in keeping with the VACTERL association. Molecular
      studies demonstrated that both are homozygous for IVS4 + 4 A-->T, a mutation in
      the Fanconi anemia complementation group C gene. This is the first molecular
      proof that VACTERL with hydrocephalus may be the result of severe Fanconi anemia.

PMID- 8986285
TI  - Giorgio Filippi, April 4, 1935-January 19, 1996.

PMID- 8986286
TI  - Trisomy 1 in a clinically recognized pregnancy.

PMID- 8986288
TI  - Osteocraniostenosis vs. severe Hallermann-Streiff-Francois syndrome.

PMID- 8986287
TI  - FISH characterization of small supernumerary marker chromosomes in two Prader
      Willi patients.
AB  - A small supernumerary chromosome was observed in two Prader-Willi syndrome (PWS)
      patients. The clinical diagnosis of PWS was confirmed by the ascertainment of the
      deletion of region 15q11-13 in one case and uniparental disomy (UPD) of the same
      region in the other. The markers were negative for dystamycinA/DAPI banding, did
      not contain NOR-positive satellites, and had an appearance consistent with a very
      small ring chromosome. Fluorescent in situ hybridization (FISH) analysis with the
      "all human centromere" probe indicated the presence of centromeric sequences in
      both markers. Chromosomal in situ suppression hybridization with chromosome
      specific libraries demonstrated that the small markers in the deleted and UPD
      patient originated from chromosome 15 and X, respectively. To the best of our
      knowledge these are the only PWS patients reported with a supernumerary marker
      chromosome other than inv dup(15) characterized by FISH.

PMID- 8986289
TI  - Major central nervous system malformation in "micromelic dwarfism with cone
      epiphyses, metaphyseal dysplasia and vertebral segmentation defects".

PMID- 8986290
TI  - The atrioventricular canal defect is the congenital heart disease connecting
      short rib-polydactyly and oral-facial-digital syndromes.

PMID- 8986291
TI  - MIB1 in colorectal carcinomas: its evaluation by three different methods reveals
      lack of prognostic significance.
AB  - Immunohistochemically detected MIB1 has been determined in a series of 106
      colorectal carcinomas with three different evaluation methods (semiquantitative
      estimation, evaluation by image analysis, and cell count). Although the
      semiquantitative estimation correlated significantly with results obtained by
      image analysis (R = 0.8), both methods were only poorly associated with MIB1
      counts (R = 0.5). Additionally, all three methods revealed no statistical
      correlation of MIB1 with the clinical outcome of the respective patients. Our
      results indicate a pronounced heterogeneity of MIB1 in colorectal adenocarcinoma,
      thus leading, irrespectively of the evaluation method used, to non-representative
      results with lack of clinical relevance.

PMID- 8986293
TI  - Differential diagnosis of malignant and reactive cells from serous effusions:
      image and texture analysis study.
AB  - The interrelationship of textural primitives which define morphological texture
      can be estimated by quite different descriptors; the discriminant value of which
      varies considerably. In the present study three different approaches to the
      texture analysis of nuclear chromatin were assayed to correctly allocate 332
      cells from a pool obtained from serous effusions (six malignant mesotheliomas,
      six reactive mesothelial proliferations and five pleural metastases of lung
      adenocarcinoma). In all cases, initial cytological diagnosis posed considerable
      problems and final diagnosis was established by histologic examination of
      surgical specimens. The three approaches were based on binarization of the image
      obtained by edge detection, gradient analysis and pattern spectrum by
      morphological opening-closing, respectively. Characteristics afforded by each
      method were: (a) spatial distribution of heterochromatin, besides geometric
      features, (b) features related to transitions and contrast between dark and light
      chromatin primitives, and (c) granulometric characteristics of the theoretically
      biphasic heterochromatin-euchromatin image defined by mathematical morphology.
      The three methods were applied to the raw grey-tone image and did not require
      interactive handling. Although each of the three approaches yielded relatively
      satisfactory results, with percentages of well-classified cells in the test set
      ranging from 61.45 to 67.47, the best results (78.31% of well-classified cells)
      were obtained taking into consideration the three types of variables (area, 2nd
      opening, 5th closing, and S.D. of the amplitude image). A point to be stressed is
      the considerably high proportion of correctly-allocated reactive mesothelial
      cells (82.0%) in a field where subjective assessment commonly yields rather poor
      results. Nevertheless, classification yielded 14.8% and 3.3% false positives as
      adenocarcinomatous and malignant mesothelioma cells, respectively. In the
      theorectical situation devised in the study, results on a cell-by-cell basis
      encouraging and suggest that a textural approach might be useful in a dedicated
      expert system or on a more real case-by-case basis.

PMID- 8986292
TI  - Expression of heat shock protein 70 (HSP70) and EBV latent membrane protein 1
      (LMP1) in Reed-Sternberg cells of Hodgkin's disease.
AB  - Tissue sections embedded in paraffin and fixed in formalin from 65 patients with
      Hodgkin's disease (HD) were examined for the presence of heat shock protein 70
      (HSP70) and Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1)
      using avidin-biotin immunoperoxidase complex technique. The staining results in
      Reed-Sternberg (R-S) cells and their variants were evaluated independently. HSP70
      expression was found in R-S cells in 55 cases (85%) of HD examined and the
      frequency of HSP70 positive cases was significantly higher than that of HSP70
      negative cases (P < 0.01). This protein was present in pathogenic cells in 9/12
      cases (75%) of lymphocyte predominant Hodgkin's disease (LPHD), 21/27 cases (78%)
      of mixed cellularity Hodgkin's disease (MCHD), 10/10 cases (100%) of lymphocyte
      depleted Hodgkin's disease (LDHD) and 15/16 cases (94%) of nodular sclerosing
      Hodgkin's disease (NSHD). The association between HSP70 expression and HD thus
      appeared to be more frequent in patients wish LDHD and NSHD subtypes, although
      examples of HSP70-positive tumors were found in all histological subtypes.
      Studies of non-neoplastic lymphoid tissues demonstrated that centroblasts (large
      lymphocytes in germinal centers) were constantly positive; occasional histiocytes
      revealed variable reactivity for.

PMID- 8986294
TI  - Flow cytometric DNA analyses of 105 fresh hydatidiform moles, with correlations
      to prognosis.
AB  - Cellular DNA contents of consecutive hydatidiform moles were analysed by flow
      cytometry of unfixed samples, freed of maternal tissue and treated with detergent
      and trypsin, using two external controls. DNA-diploidy was found in 62 moles, DNA
      triploidy in 42 and DNA-tetraploidy in one. Two non-molar placentas and two
      invasive moles were found to be DNA-diploid. In 28 of 42 DNA-triploid moles,
      trophoblastic hyperplasia was not noted, making the discrimination between
      vesicular abortions with or without trophoblastic hyperplasia unwarranted on
      genetic grounds. A good fit was obtained to a distribution with one G0-1 peak in
      49 cases, whereas 60 cases showed two peaks. Technical artifacts, created by flow
      cytometry, were excluded. Differences in the nuclear accessibility for the dye
      and degradation of DNA are unlikely causes of this heterogeneity. The existence,
      in vivo, of two or more cell populations with different DNA contents is a
      reasonable explanation. The criteria for persistent trophoblastic disease were
      standardised. Eight cases of persistent trophoblastic disease were observed among
      the 62 DNA-diploid moles (13%); no case was observed after DNA-triploid or DNA
      tetraploid moles. Combining these data, with those of other studies where ploidy
      was determined using optimal techniques [10,13], allows the calculation of 95%
      confidence-limits for the risk of persistent trophoblastic disease after a
      triploid mole to 0-2.7%.

PMID- 8986295
TI  - Cell cycle analysis of normal, atrophic, and hyperplastic breast epithelium using
      two-color multiparametric flow cytometry.
AB  - We performed two-color flow cytometric synthesis phase fraction (SPF)
      determinations on cytokeratin-labeled benign epithelial populations from 142
      breast specimens (41 mastectomy, 70 diagnostic biopsy, 31 reduction mammoplasty).
      There was wide variability of SPF, ranging from 0.1 to 3.5%, with a frequency
      distribution skewed to higher values (mean 0.75%, median 0.5%). The mean SPE for
      women less than 29 years was 0.91%, vs. 0.89% for 30-42 years, 0.66% for 43-49
      years, and 0.56% for > or = 50 years (P = 0.05). Histologically atrophic tissue
      samples exhibited a mean SPF approximately half that of morphologically normal
      tissue from premenopausal age women (0.79% vs. 0.36%, P = 0.02). Tissues showing
      histologically proliferative fibrocystic features had a greater mean SPF than non
      proliferative fibrocystic tissues (0.59% vs. 0.92%); however, due to the wide
      spread of values within each of these categories, this difference was not
      statistically significant and neither group was significantly different from
      'normal' tissue samples. Patients with histologically normal breast tissue,
      though, were significantly younger (mean = 34.6 years) than those with
      fibrocystic changes (non-proliferative mean = 53.4 years vs. proliferative mean =
      42.8 years, P = 0.005). Synchronous right- and left-sided specimens obtained from
      reduction mammoplasty demonstrated significantly correlated SPF determinations (R
      = 0.77). We conclude that selective analysis of epithelial populations using two
      color flow cytometry provides cell cycle information in benign breast tissue
      which is analogous to that obtained by labor-intensive nucleotide labeling
      studies. This study also confirms the biologic variability and age-dependence of
      breast epithelial proliferation. Finally, the data imply that derangements of
      cell proliferation in fibrocystic conditions are heterogeneous, complex and
      incompletely correlated with histologic parameters such as hyperplasia.

PMID- 8986296
TI  - Gastrocnemius muscle length in relation to knee and ankle joint angles:
      verification of a geometric model and some applications.
AB  - BACKGROUND: For understanding the relationship between skeletal muscle
      architecture and muscle function in vivo, the development of accurate geometric
      models relating muscle length to joint angles is crucial. Therefore, a geometric
      model of the calf of mammals was developed to predict the length of the
      gastrocnemius muscle-tendon complex from knee and ankle angles. METHODS: The
      model requires three skeletal length measurements (radius of femoral condyle,
      ankle lever, and tibia length) to predict muscle-tendon length. The model was
      tested on the hopping mouse (Notomys alexis) by comparing polynomial fittings
      with geometrical fits of muscle length-joint angle measurements (i.e., the
      equation of the geometric model was used for least square fitting of the data).
      The model was applied to the hopping mouse and the rat to study (in vivo) joint
      angle-muscle length-force relationships. RESULTS: It appeared that small and, on
      average, statistically nonsignificant length adjustments of the skeletal lengths
      were needed for the geometrical fit. Combinations of joint angles that normally
      occur during locomotion yielded muscle lengths close to optimum (i.e., with the
      highest isometric force potential). CONCLUSIONS: By relying on the geometry of
      the animal's leg, the calculated moment arms of the model appeared more reliable
      than those calculated from the polynomial fit. It was concluded that the
      architecture regarding length-force properties of the gastrocnemius muscle in
      both hopping mouse and rat is well adapted for the locomotion patterns.

PMID- 8986297
TI  - Ultrastructural and functional analyses of nephropathy in calmodulin-induced
      diabetic transgenic mice.
AB  - BACKGROUND: Previous animal models of diabetic nephropathy have used diabetic
      animals for which the underlying defect was either uncertain or the diabetes was
      induced by potentially specific toxins. In this report, we describe the renal
      abnormalities in a transgenic mouse model that develops early-onset diabetes due
      to overexpression of calmodulin in pancreatic beta cells. METHODS: Renal tissues
      were collected from normal and transgenic mice at 112, 182, and 300 days. These
      were prepared for light microscopic observation, stained with polyethylenimine
      (for anionic sites), or rendered acellular by detergent extraction prior to
      observation by transmission and scanning electron microscopy. Morphometric
      analysis of glomerular basement membrane thickness was carried out by the
      "orthogonal intercept" method. Twelve-hour urine samples of fed and fasting mice
      were collected for urine volume and glucose and protein analyses. Blood glucose,
      blood urea nitrogen, serum insulin, and creatinine were determined in 60-90-day
      old and 255-day-old mice by established methods. RESULTS: Morphometric analyses
      revealed age-related and transgene-related increases in glomerular basement
      membrane thickness. A 22% increase in transgenic diabetics over controls was seen
      at 112 days of age that developed to increases of 43% and 37% at 182 and 300 days
      of age, respectively. Mesangial matrix area was also increased markedly in
      transgenic mice. Surprisingly, even in the oldest diabetic mice, there was no
      reduction in anionic sites. Moreover, despite an eightfold increase in urine
      volume, these mice did not become significantly proteinuric. CONCLUSIONS: These
      results indicate that proteinuria of diabetes may be delayed or prevented by
      maintenance of a normal complement of glomerular basement membrane anionic sites.
      They also demonstrate that transgenic mice can provide a valuable model for
      discriminating between different aspects of diabetic nephropathy.

PMID- 8986298
TI  - Changes in vascular permeability and deciduoma formation during the peri
      implantation period of the rat in response to exogenous gonadotropins.
AB  - BACKGROUND: Permeability of thin-walled vessels of the endometrium could be a
      prerequisite for deciduoma formation. Exogenous gonadotropins alter endometrial
      morphology and inhibit vascular permeability on the day of implantation. The aim
      of this study was to investigate the effect of exogenous gonadotropins on
      vascular permeability in the peri-implantation period and relate this to
      deciduoma formation. METHODS: Female rats were hyperstimulated with follicle
      stimulating hormone and human chorionic gonadotropin prior to mating. Control
      animals were not injected. Endometrial tissue was collected at 4.5, 5.5, and 6.5
      days after mating. Tissue was processed for electron microscopy. RESULTS: The
      presence of thin-walled fenestrated vessels and decidualised stromal cells were
      found in all control groups. With the exception of one fenestration, which
      occurred in a vessel from one hyperstimulated animal on 5.5 days of pregnancy, no
      fenestrations were found in the vessels of hyperstimulated animals.
      Decidualisation of stromal cells did not occur in these animals. CONCLUSION:
      Hyperstimulation with exogenous gonadotropins inhibits vascular permeability and
      subsequent decidualisation. Implantation thus fails to occur.

PMID- 8986299
TI  - Sperm maturation in rhesus monkey: changes in ultrastructure, chromatin
      condensation, and organization of lipid bilayer.
AB  - BACKGROUND: The changes in ultrastructure, lipid organization, chromatin
      decondensation, and denaturation of rhesus monkey spermatozoa during epididymal
      maturation were studied. This study would provide background information that
      would be useful to evaluate adverse effects, if any, caused by the use of
      contraceptive agents. METHODS: Adult sexually mature rhesus monkeys were
      castrated under ketamine anesthesia. The epididymis was divided into initial
      segment, caput, corpus, and cauda epididymides. To study changes in lipid
      organization of the sperm plasma membrane during epididymal transit, spermatozoa
      from different epididymal segments and ejaculated spermatozoa were exposed to
      merocyanine 540 (MC 540). The changes in chromatin denaturation and
      decondensation were assessed by using the nucleic acid-specific fluorochromes,
      acridine orange, and ethidium bromide, respectively, prior to and after exposure
      to dithiothreitol (DTT). RESULTS: Testicular spermatozoa (approximately 40%)
      showed localization of MC 540 mainly in the midpiece, whereas remaining sperm did
      not localize MC 540. Spermatozoa from the initial segment of the epididymis
      showed uniform distribution of MC 540 localization in the head and midpiece. A
      pattern of localization of MC 540 similar to mature caudal and ejaculated sperm
      in which the staining was restricted to the acrosome and the midpiece first
      appeared in a small percentage of caput spermatozoa and was completed during
      transit through the corpus epididymidis. Mature spermatozoa from cauda
      epididymidis, vas deferens, and ejaculate did not undergo chromatin denaturation
      even after exposure to 10 mM DTT, unlike sperm from testis, initial segment, and
      caput epididymidis. Spermatozoa exposed to DTT showed chromatin decondensation;
      maximum decondensation was seen in testicular sperm and a decrease in the
      percentage of sperm, showing decondensation, occurred during epididymal transit.
      Ultrastructural studies showed that spermatozoa undergo structural changes during
      sperm maturation. CONCLUSIONS: The present study shows that rhesus monkey
      spermatozoa undergo reorganization of the plasma membrane lipids and
      stabilization of disulfide linkages during epididymal transit. The results would
      be of use in evaluating the action of potential male contraceptive drugs on
      epididymal spermatozoa.

PMID- 8986300
TI  - Porcine lingual taste buds: a quantitative study.
AB  - BACKGROUND: Taste buds on the pig tongue have been neither studied in detail nor
      quantified. We have counted the numbers of fungiform and vallate papillae,
      estimated their taste bud densities, and computed numbers of taste buds per
      volume of papilla on porcine tongue. Pig was chosen for this work because it is
      an omnivorous animal, and is one of the better models for study of nutrition
      related problems in omnivorous human beings. METHODS: Tongues from three adult
      pigs were obtained from the local abattoir, fixed in 10% neutral buffered
      formalin, and mapped for the fungiform and vallate papillae. Serial 15 microns
      sections were prepared from blocks containing the papillae, and were stained by H
      & E. Density and volume of the taste buds were estimated using a Bioquant system.
      RESULTS: Eight hundred fifty and 826 fungiform papillae were observed on tongue I
      and II, respectively; numerically vallate papillae were 1, 2, and 2 for tongue I,
      II and III, respectively. Number of taste buds per fungiform papilla was
      considerably less on the dorsal surface of the tongue (3.88/papilla) than on the
      lateral side (22.11/papilla). Vallate papillae contained significantly more taste
      buds, a mean of 732.67 per papilla (t = 14.27; df = 6; P = < 0.05), than in the
      fungiform papillae. Density of the buds per volume of fungiform papilla was
      notably less on the dorsum (13.69) than on the lateral border (30.08). The
      density of vallate papillae taste buds per volume of the papilla was
      significantly greater than the lateral and dorsal papillae taste bud density (t =
      4.28; df = 6; P < or = 0.05). CONCLUSIONS: The present results are relevant to
      studies on variations of taste sensitivity among regions of the tongue.

PMID- 8986301
TI  - Protein gene product 9.5-like and calbindin-like immunoreactivity in the nasal
      respiratory mucosa of perinatal humans.
AB  - BACKGROUND: Protein gene product 9.5 (PGP) and calbindin-D28k (calbindin) are
      neuroendocrine markers that have been localized to neuroendocrine cells in the
      developing tracheobronchial epithelium. Neuroendocrine cells may play some role
      in the development of the tracheobronchial epithelium. Little is known about the
      development of the nasal respiratory epithelium (RE). METHODS: Nasal respiratory
      mucosa from fetal and newborn humans was examined to determine immunoreactivity
      for PGP and calbindin. RESULTS: At all stages studied, cells of different
      morphologies displayed PGP-like immunoreactivity (-LI) and calbindin-LI. Columnar
      immunoreactive cells for both markers predominated, but labeled cells of
      different shapes were also observed. Most labeled columnar cells were in the RE
      at its border with olfactory epithelium (OE); a few similarly labeled columnar
      cells also appeared in this OE. In the lamina propria, PGP-LI was also seen in
      numerous thin branching fibers. Some of these branches penetrated into the
      epithelium, where fiber varicosities appeared to contact cells, some of which
      also exhibited PGP-LI. CONCLUSION: This study demonstrates that during
      development the human nasal RE contains different cell types, as illustrated by
      the assortment of epithelial cells displaying PGP-LI and calbindin-LI among
      unlabeled cells. Because PGP and calbindin immunoreactivities were found within
      neuroendocrine cells in previous studies, the present results indicate that the
      developing human nasal RE also may support a number of neuroendocrine cells.
      Furthermore, at least some of these cells may form synaptic contacts with nerve
      fibers from outside the epithelium.

PMID- 8986303
TI  - The structure of superficial lymphatics in the human thigh: precollectors.
AB  - BACKGROUND: Little is known about the morphology of precollectors, the lymphatic
      vessels connecting the absorbing and the collecting vessels, which are regarded
      as the initial drainage routes of lymph. The aim of this study was to describe
      the structural features of human precollectors. METHODS: Samples of fat from
      around the saphenous veins were obtained from patients undergoing varicotomy, and
      serial sections were observed under light and transmission electron microscopy.
      Tridimensional reconstructions were also obtained by computer analysis. RESULTS:
      Precollectors were characterized by an irregular and discontinuous arrangement of
      smooth muscle cells in their wall. This arrangement was unrelated to the site of
      valves. When present, muscular elements were arranged helicoidally, as shown in
      tridimensional reconstructions. Under transmission electron microscopy, the
      endothelium of precollectors was similar to that of absorbing lymphatic vessels,
      irrespective of the presence of smooth muscle cells, and was thin, rich in
      pinocytotic vesicles, supported by a discontinous basal lamina, and connected by
      anchoring filaments to the surrounding connective tissue. Myoendothelial contacts
      were frequent. Valves were similar to those of collecting vessels, except for the
      presence of numerous zonulae adherentes connecting the characteristic "tip cells"
      of the free edge. CONCLUSIONS: Human thigh precollectors are characterized by the
      alternation of portions with a well-developed muscular coat and portions with an
      absorbing structure. These morphological features suggest that the precollectors
      contribute to fluid absorption and lymph propulsion. The frequent myoendothelial
      contacts suggest that smooth muscle contraction is regulated locally.

PMID- 8986302
TI  - Cardiac-like musculature of the intrapulmonary venous wall of the long-clawed
      shrew (Sorex unguiculatus), common tree shrew (Tupaia glis) and common marmoset
      (Callithrix jacchus).
AB  - BACKGROUND: The cardiac-like musculature is distributed not only in the heart
      wall but also in the intrapulmonary venous wall in a few species of insectivores.
      It has been suggested that the evolutionary origin of venous cardiac-like
      musculature may be traceable to a basic stock of certain mammalian lines of
      descent. So, it is important to clarify whether the musculature may be a common
      structure in lower mammals from insectivores to primates and to examine the
      functional significance of the structure. METHODS: The distribution of cardiac
      like musculature in the intrapulmonary venous wall of the long-clawed shrew
      (Sorex unguiculatus), common tree shrew (Tupaia glis), and common marmoset
      (Callithrix jacchus) was observed by light and electron microscopy. The presence
      of atrial natriuretic polypeptide (ANP) was examined in the musculature by
      immunohistochemistry. RESULTS: All three species contained cardiac-like myocytes
      in the tunica media of intrapulmonary venous wall. In the common tree shrew and
      the common marmoset, cardiac-like musculature was found in the small
      intrapulmonary vein of 150-200 microns in diameter, while, in the long-clawed
      shrew, it was distributed even in the intrapulmonary vein of 30 microns in
      diameter. Ultrastructure of myocytes was fundamentally similar to that of atrial
      myocytes in the long-clawed shrew and the common tree shrew. The presence of
      atrial natriuretic polypeptide (ANP) was also demonstrated by
      immunohistochemistry in the intrapulmonary venous walls of common tree shrews.
      CONCLUSIONS: The results indicate that the pulmonary venous cardiac-like
      musculature occurs in the lower eutherian mammals from insectivores to primitive
      primates. The musculature is thought to act as a regulatory pump in pulmonary
      circulation and as an endocrine apparatus of ANP.

PMID- 8986304
TI  - Afferent portal venous system in the mesonephros and metanephros of chick
      embryos: development and degeneration.
AB  - BACKGROUND: In the chick embryo, both mesonephros and metanephros have a renal
      portal system. The classical literature gives uncertain answers about the
      development and degeneration of the meso- and metanephric portal venous system.
      Some mesonephric vessels present angiogenic processes to colonize the
      metanephros, while others show signs of degeneration and disappear together with
      the mesonephros. The adult avian kidney has a conspicuously placed valve, the
      renal portal valve. The development of this functionally important renal portal
      valve has not yet been studied in detail. METHODS: Scanning electron microscopy
      of vascular corrosion casts has been used in this study. Strong mesonephric
      degeneration as well as metanephric growth and maturation occur in the
      developmental stages selected for this investigation (7.5, 9, 11, 14, and 21 days
      of incubation). RESULTS: The mesonephric afferent venous system in the chick
      embryo is supplied by two vessels, the posterior and the anterior mesonephric
      portal veins. The posterior mesonephric portal veins show a similar pattern to
      the anuran (amphibian) kidney. The anterior mesonephric portal vein has not
      previously been described. Constrictions were found in this vessel, a probable
      sign of subsequent degeneration. The metanephric afferent venous system is also
      supplied by two vessels: the caudal and cranial metanephric portal veins. The
      caudal metanephric portal vein is derived from the postcardinal vein. The cranial
      metanephric portal vein grows independently throughout the development of the
      mesonephric vascular system. It is connected to the vertebral venous sinus
      already at the beginning of its development. The renal portal valve first appears
      as a capillary network that communicates with the developing afferent and
      efferent metanephric venous systems. This capillary network later develops to a
      venous valve. The metanephric afferent venous system shows typical angiogenic
      signs in corrosion cast, such as nodular protrusions, holes, and enlarged
      vessels. CONCLUSIONS: The postcardinal vein first supplies only the mesonephric
      tissue as a portal vessel. Then it becomes a common source for both kidney
      generations. Finally it supplies only the metanephric tissue with venous blood.
      However, two independent vessels were found to supply the cranial renal regions:
      the anterior mesonephric portal vein and the cranial metanephric portal vein.

PMID- 8986305
TI  - Polysialylated NCAM expression on endocardial cells of the chick primary atrial
      septum.
AB  - Septation of the tubular heart to form the multi-chambered heart involves
      endocardial cell mesenchymal transformation at discrete sites. These sites
      include the crests of endocardial cushions at the atrioventricular junction,
      crests of the spiral ridges within the outflow tract, and the leading edge of the
      atrial septum. The factors involved in this multi-step inductive process appear
      to include the neural cell adhesion molecule (NCAM). The down-regulation of NCAM
      coincident with mesenchymal transformation has been documented at the
      atrioventricular cushion tissue. In view of the function-regulation properties of
      polysialylated NCAM (PSA-NCAM), we hypothesized that this form of NCAM would be
      playing a role during the dramatic changes in cell-cell interactions occurring in
      the endocardium at the leading edge of the primary atrial septum. Chicken hearts
      at stages during primary atrial septum development were fixed with
      paraformaldehyde and either immunofluorescently stained for the light microscope
      analysis or immunoperoxidase stained for ultrastructural analysis. A monoclonal
      antibody to an NCAM polypeptide epitope (5E) was used to detect all forms of
      NCAM, while a monoclonal to the polysialic acid (5A5) was used to detect that
      subset of NCAM which is highly polysialylated (PSA-NCAM). By light microscope
      level analysis, an increase in immunostaining for NCAM and the appearance of PSA
      NCAM was detected on embryonic chicken endocardial cells at the leading edge of
      the growing atrial septum. The ultrastructural analysis revealed that there is
      also a change in the pattern of NCAM and PSA-NCAM from a polarized localization
      to a more ubiquitous distribution over the endocardial cell surface as these
      cells send out processes, form multiple layers, and sink or move into the
      underlying extracellular matrix. PSA-NCAM was also detected along cell
      appositions of cells within the matrix. Both NCAM and PSA-NCAM levels were
      reduced on cells deep within the matrix. These findings indicate that during
      primary atrial septation, PSA-NCAM may be deployed on endocardial epithelial
      cells in order to down-regulate cell-cell interactions and allow the detachment
      and migration of some of these cells into the underlying matrix.

PMID- 8986306
TI  - Formation of reticulated endoderm, Reichert's membrane, and amniogenesis in
      blastocysts of captive-bred, short-tailed fruit bats, Carollia perspicillata.
AB  - BACKGROUND AND METHODS: As part of an effort to develop the short-tailed fruit
      bat (Carollia perspicillata) as a new animal model for the study of interstitial
      implantation and trophoblast-uterine interactions, early embryogenesis was
      examined histologically and ultrastructurally in captive-bred females at
      different intervals after the first appearance of spermatozoa in daily vaginal
      smears (day 1 postcoitum [p.c.]). RESULTS: In most of the early uterine embryos
      examined on days 16-18 p.c., much of the endoderm appeared as a reticulated
      meshwork; however, a unilocular yolk sac was formed prior to the development of
      any mesoderm. Early blastocysts of Carollia were also unusual in that endoderm
      surrounded much of the inner cell mass (ICM), Reichert's membrane continued over
      the dorsal side of the ICM, and basal laminalike material was observed around
      many of the endoderm and epiblast cells. A primordial amniotic cavity was formed
      between days 19 and 26 p.c. by cavitation. The first mesoderm appeared between
      days 23 and 26 p.c., concommitant with the development of an embryonic shield.
      CONCLUSION: The unusual reticulated appearance of early endoderm in Carollia,
      which is reminiscent of that seen in early human blastocysts, may be attributable
      to constraints imposed on growth of the blastocyst by the site and mode of
      implantation, temporary retardation of trophoblastic invasion by the basal
      laminae of endometrial epithelial elements, and endodermal proliferation in
      anticipation of rapid yolk sac expansion. Reichert's membrane appears to play an
      important role in this species in tethering the ICM and embryonic shield to the
      developing placenta prior to the formation of significant amounts of mesoderm.

PMID- 8986307
TI  - Developmental alterations in casein kinase 2 activity during the morphogenesis of
      quail secondary palate.
AB  - BACKGROUND: During the progression of avian secondary palate morphogenesis, the
      rate of cell proliferation declines, whereas the production and accumulation of
      extracellular matrices increases. To investigate the regulation of these events,
      we examined the quail secondary palate for the activity of casein kinase 2 (CK
      2), a pleiotropic serine/threonine second messenger independent enzyme implicated
      in cell growth and differentiation. METHODS: Quail palatal shelves were dissected
      between days 5 and 9 of incubation, which is the period of palate morphogenesis
      in quail, and prepared either for light microscopic observations or homogenized,
      cleared by ultracentrifugation, and then subjected to fractionation on a MonoQ
      column by fast protein liquid chromatography and Western immunoblotting. RESULTS:
      Histological examination showed that the palatal shelves appeared on day 5 of
      incubation and approximated by day 8 of incubation. Fractionation of palate
      extract using a Mono-Q column revealed the presence of a major peak of phosvitin
      phosphotransferase activity which eluted with 0.5 M NaCl. This activity peak
      coincided with the presence of a 42 kDa subunit of CK 2 as determined by Western
      blotting with a CK 2 specific antibody. The CK 2 activity towards phosvitin was
      elevated on days 5 and 6 and then rapidly declined by day 9. The decrease in CK 2
      activity did not correlate with a decrease in CK 2 protein during palate
      development indicating that the differential activity of the CK 2 enzyme observed
      during quail palate development may be due to post-translational modifications of
      the enzyme. A high positive correlation was found between the CK 2
      phosphotransferase activity and both the proliferation index and DNA synthesis
      during palate development. CONCLUSION: On the basis of literature analysis and
      the results of the present study, it was suggested that the activity of CK 2 may
      be regulated along with protein kinase A to coordinate cell proliferation and the
      synthesis of extracellular matrices during palate development in quail.

PMID- 8986308
TI  - Microtopography of the autonomic nerves in the rat knee: a fluorescence
      microscopic study.
AB  - BACKGROUND: The autonomic innervation of the joint is involved in different
      functions, such as sensory inputs, modulation of the function of immune cells,
      and trophic actions. To have a basis for further studies of the arthritic knee
      joint we have investigated the topographical distribution of different
      neuropeptides in knees of newborn and adult rats and in adult rats after
      arthritis induction. METHODS: The distribution of the neuropeptides calcitonin
      gene-related peptide (CGRP), neurokinin A (NKA), substance P (SP), and
      neuropeptide Y (NPY) was analyzed using fluorescence immunohistochemistry.
      Samples were investigated after fixation by perfusion and decalcification by a
      special method which allows studies in bone tissue. Vascular structures were
      analyzed by scanning electron microscopy (SEM) of vascular resin casts. RESULTS:
      In all tissues of the joint (synovial membrane, vessels, fibrous structures,
      bone, and cartilagineous tissues) CGRP and NKA are the most frequent
      neuropeptides. They are localized in free or perivascular fibers predominantly
      around arteries and arterioles. The NPY-ergic perivascular fibers even enter the
      vessel wall. Generally, SP-ergic fibers occur rarely. Free NKA- and CGRP-ergic
      nerve fibers spread out in the synovial lining layer reaching the synovial cavity
      and the outer layers of the articular and metaphyseal cartilage. In the
      cartilagineous tissue these nerves contact the chondrocytes. The density of NKA-
      and CGRP-immunoreactive fibers is lower in newborn rats than in adult rats. Six
      hours after arthritis induction SP-, NKA-, and CGRP-immunoreactivity is enhanced
      especially in perivascular fibers. The related vessels are dilated substantially.
      CONCLUSIONS: The distribution pattern of the autonomic nerves found in this study
      might reflect the functions of these nerves: control of the microcirculation,
      sensory and even trophic functions. The new finding of CGRP- and NKA-ergic fibers
      in the outer layer of the cartilage can also have implications for the
      pathogenesis of rheumatoid arthritis.

PMID- 8986309
TI  - Effects of aging on numbers and sizes of neurons in histochemically defined
      subregions of monkey striate cortex.
AB  - BACKGROUND: In addition to its horizontal layers, primate striate cortex has a
      vertical modular organization. Among the vertical modules are histochemically
      defined areas of high and low cytochrome oxidase labeling in the supragranular
      layers, referred to, respectively, as blobs and interblobs. Cytochrome c oxidase
      (CO) blobs and interblobs differ in their inputs from the magnocellular and
      parvocellular visual pathways, their physiological properties, and many aspects
      of their neurochemistry. The present study investigated whether aging
      differentially affects neuron numbers or sizes in the supragranular blobs or
      interblobs. METHODS: The right hemisphere from three young adult (5.2-12.4 years)
      and four old (24.0-26.7 years) rhesus monkeys was used. Tangential sections
      through the central visual-field representation were stained for CO and
      counterstained with cresyl violet. Montages were constructed through cortical
      layers 2 and 3, and neuron counts and size measurements were made in blob and
      interblob regions using stereological procedures that yield unbiased estimates.
      Blob density also was calculated. RESULTS: CO blob density was 3.76/mm2 in young
      adults and 3.95/mm2 in old animals, a difference that was not statistically
      significant. Neuron soma sizes also did not differ significantly between young
      adult and old animals or between blob and interblob regions. In addition, neuron
      density was not significantly different between young adult and old animals.
      However, independent of age, neuron density was significantly higher in the
      center of interblobs (394,058 cells/mm3) than in the center of blobs
      (333,638/mm3). CONCLUSIONS: Our results and those of previous studies (Vincent et
      al. 1989. Anat. Rec. 223:329-341; Peters and Sethares. 1993. Anat. Rec. 236:721
      729) suggest that aging has little or no effect on the densities or sizes of the
      different functional or morphological types of neurons that exist in the
      different cortical layers or in the different vertical modules marked by CO blobs
      and interblobs. These findings are consistent with the results of our previous
      anatomical and physiological studies of the rhesus monkey retina and lateral
      geniculate nucleus. These results suggest that the retinogenic-ulostriate
      pathways are relatively unaffected by aging in the rhesus monkey.

PMID- 8986310
TI  - Distribution of the arterial supply to the vomeronasal organ in the cat.
AB  - BACKGROUND: The main goal of this work was to investigate the general
      distribution of arterial blood around and inside the vomeronasal organ (VNO) of
      the cat. METHODS: Macro- and microdissection methods together with light and
      scanning electron microscopy were used. Heads were injected with an India
      ink/agar mixture (the VNO subsequently being cut in transverse, sagittal and
      horizontal sections), with clear latex (the VNO subsequently being cut in
      transverse sections), or with an epoxy resin to obtain casts for examination by
      scanning electron microscopy. RESULTS: Dissection and microdissection show that
      the infraorbital, minor palatine, and descending palatine arteries have a common
      origin, rostral to the Rete mirabile arteria maxillaris. In transverse series and
      in the rostral half of the VNO, an arteriole is consistently observed between the
      vomeronasal duct and the lateral sheet of the vomeronasal cartilage. In this same
      segment, arterial branches with different orientations (perpendicular,
      horizontal, or transverse with respect to the main axis of the organ) are
      observed. Scanning electron microscopy of arterial casts shows that arterial
      vessels of the mucosa of the nasal septum have a direct relationship with the
      VNO. CONCLUSIONS: Branches of the sphenopalatine artery are the chief route of
      blood supply to the VNO. The vomeronasal parenchyma has few arterial vessels, and
      these are usually situated in the same position. Differences observed between the
      arteries inside and outside the VNO and the dilation of both by isoproterenol
      support the idea that the VNO is similar to erectile tissue organs and that it
      may act as a physiological pump.

PMID- 8986311
TI  - Modified Sihler's technique for studying the distribution of intramuscular nerve
      branches in mammalian skeletal muscle.
AB  - BACKGROUND: A largely forgotten technique initially designed by Sihler for
      staining nerve tissue has not been fully explored for staining intramuscular
      nerve branches in skeletal muscles. METHODS: Fresh, long heads of triceps from
      locally bred New Zealand white rabbits were used for this study. Immediately
      after their removal, the muscles with their motor nerve branches from the radial
      nerve were fixed in 10% unneutralized formalin, followed by maceration and
      depigmentation in 3% aqueous potassium hydroxide, decalcification in Sihler's
      solution I, micro-dissection, staining in Sihler's solution II, destaining in
      Sihler's solution I, neutralization in 0.05% lithium carbonate, and clearance in
      increasing concentrations of glycerin. RESULTS: A clear three-dimensional
      orientation of the distribution of the intramuscular nerve branches within the
      muscle belly was visualized. It was found in all specimens that the long head of
      triceps in the rabbit was constantly innervated by three main intramuscular nerve
      branches and each of them supplied different amounts of muscle fibers with some
      variation. CONCLUSION: The Sihler's neural staining technique can be applied to
      the study of the distribution of intramuscular nerve branches in limb skeletal
      muscles. Extension of the technique may be utilised in the identification of
      neuromuscular compartments in skeletal muscles. Such information may be usefully
      applied in free muscle transfer of segments of skeletal muscle.

PMID- 8986312
TI  - Subjective muscle weakness and hypotonia during clozapine treatment.
AB  - Four cases of patients who described an unpleasant subjective experience of
      weakness and reduced muscle tone during treatment with clozapine are presented.
      An exacerbation of muscular dystrophy during clozapine treatment is also
      described. It is hypothesized that these adverse effects are related to the
      muscle relaxant properties of clozapine. The differential diagnosis of sedation,
      fatigue, asthenia, and reduced muscle tone is discussed.

PMID- 8986313
TI  - Adjunctive loxapine in a clozapine-resistant cohort of schizophrenic patients.
AB  - The purpose of this trial was to assess the potential utility of adjunctive
      treatment with a typical neuroleptic for patients with refractory psychosis
      insufficiently responsive to clozapine alone. Seven chronic schizophrenic or
      schizoaffective patients who remained stabilized for at least 9 months on
      clozapine received open clinical trials with adjunctive loxapine lasting from 18
      to 50 weeks. Their symptoms were documented with periodic Brief Psychiatric
      Rating Scale assessments. All patients improved at least somewhat and two
      improved remarkably. In the four cases in which the assessment was made, the
      loxapine had no apparent effect on plasma clozapine levels. We conclude that
      adjunctive treatment with typical neuroleptics for patients with an incomplete
      response to clozapine merits further investigation.

PMID- 8986314
TI  - The practical use of carbon dioxide-induced anxiety in the diagnosis and care of
      patients with panic disorder.
AB  - The authors utilized inhalation of 35% carbon dioxide and 65% oxygen as a
      diagnostic tool in the evaluation of suspected panic disorder. In two inpatients
      admitted for a medical evaluation for pheochromocytoma and carcinoid syndrome,
      respectively, a positive response to the double-blind administration of CO2/O2 or
      room air was consistent with a diagnosis of panic disorder by psychiatric
      history. In two additional patients in whom denial of mental illness was a
      psychological impediment to proper treatment, a positive CO2/O2 challenge
      resulted in therapeutic benefit.

PMID- 8986315
TI  - Treatment of depression following myocardial infarction with interpersonal
      psychotherapy.
AB  - A case history involving the treatment of a depressed patient who had suffered a
      recent myocardial infarction is described. The patient was successfully treated
      using a short, time-limited course of interpersonal psychotherapy for depression.
      The implications of postinfarction depression are discussed, as are the
      implications of the successful nonpharmacologic treatment.

PMID- 8986316
TI  - Probable nefazodone-induced mania in a patient with unreported bipolar disorder.
AB  - Nefazodone is a new antidepressant exhibiting properties of selective serotonin
      reuptake inhibition and serotonin-2 receptor antagonism. There has been only one
      other published case of induction of mania in a patient treated with nefazodone.
      This report describes a second case of probable induction of mania with
      nefazodone therapy and briefly reviews clinical and theoretical considerations
      involved in this process.

PMID- 8986317
TI  - Naloxone-reversible coma unrelated to opiate drugs.
AB  - A role for endogenous opioids in central nervous system disorders has often been
      proposed. A case report is presented of a 47-year-old male, medicated only with
      carbamazepine and lithium, who developed a precipitous alteration of
      consciousness (Glascow coma scale = 4). An extensive medical workup did not
      reveal an underlying cause. He exhibited a graded awakening with two intravenous
      doses of naloxone, which gradually reversed as the last naloxone dose was
      eliminated. Immunoassay and thin-layer chromatography of two urine samples (to
      evaluate the possibility of a medication error, alcohol ingestion, or illicit
      drug use) revealed only the presence of carbamazepine. A dysregulation of the
      endogenous opioid system is believed to underlie this episode.

PMID- 8986318
TI  - Calcium channel blockers for anxiety disorders?
AB  - The role of calcium in the etiology of anxiety has been proposed for several
      decades. Calcium channel blockers profoundly influence calcium metabolism and the
      transport of calcium. Even though the evidence for the role of calcium remains
      weak, drugs affecting calcium might be useful in the treatment of anxiety
      disorders. One of these compounds, verapamil, has been used to treat mood
      disorders. Calcium channel blockers have also been tried in other indications
      such as premenstrual syndrome, irritable bowel syndrome, schizophrenia, tardive
      dyskinesia, and Tourette's syndrome. However, the number of articles on the use
      of calcium channel blockers in the treatment of anxiety disorders is low. Three
      reports (two open, one double-blind) described some success in the treatment of
      panic disorder with verapamil, diltiazem, or nimodipine and one open-label study
      described unsuccessful treatment of anxiety and phobia with nifedipine in
      patients with various anxiety disorders. Further double-blind placebo-controlled
      studies of calcium channel blockers in the treatment of anxiety disorders are
      warranted to determine a possible role of these compounds in the armamentarium of
      antianxiety drugs.

PMID- 8986319
TI  - Risperidone: once-daily dosage.

PMID- 8986320
TI  - IL-1 beta gene expression in B cells derived from the murine MRL/lpr model of
      lupus.
AB  - The MRL/lpr model of SLE resembles human lupus in its various immunopathologic
      characteristics including the presence of high-level IgG and anti-DNA antibody
      production and multisystem organ involvement (nephritis, arthritis, and
      vasculitis). Our previous studies have shown that IL-1 overactivity in B cells
      plays a potentially important role in driving IgG and autoantibody production.
      However, the underlying mechanisms determining IL-1 overactivity are poorly
      understood. We studied IL-1 beta gene expression and transcriptional rates in B
      cells derived from old and young MRL/lpr, MRL/+ +, and non-autoimmune control
      mice using semi-quantitative RT-PCR and the nuclear run-on assay. RT-PCR
      demonstrated increased steady-state IL-1 beta gene expression in B cells derived
      from old MRL/lpr mice as compared to either young MRL/lpr or control mice.
      Furthermore, IL-1 beta gene expression in B cells was associated with the
      presence of the lpr mutation because heightened IL-1 beta message was observed in
      RNA obtained from MRL/lpr but not MRL/+ + B cells. IL-1 beta transcriptional
      rates measured by the nuclear run-on assay were very similar in B cells from old
      and young MRL/lpr and control mice. These observations suggest that IL-1
      overactivity in B cells obtained from old diseased MRL/lpr results from
      heightened IL-1 beta message, is associated with the presence of the lpr
      mutation, and is likely to reflect post-transcriptional stabilization of IL-1
      beta mRNA.

PMID- 8986321
TI  - Effects of interferon-alpha therapy on immune parameters in immune
      thrombocytopenic purpura.
AB  - Interferon-alpha (IFN alpha) has been shown to increase platelet numbers in
      patients with immune thrombocytopenic purpura (ITP), but the basis for this
      effect is not known. In this study changes in immune function were monitored
      following administration of IFN alpha to seven patients whose ITP had proved
      refractory to conventional therapy. Patients' peripheral blood mononuclear cells
      were cultured with phytohaemagglutinin and culture supernatants assayed for
      cytokine production. Production of the Th1 cytokines IL-2 and IFN-gamma was low
      in patients compared to healthy controls, and amounts of these tended to increase
      after IFN alpha therapy. In two patients high levels of IL-10 were detectable in
      culture, and these were reduced after IFN alpha. In patients who had high serum
      concentrations of IL-4 or IL-10, these were also decreased following therapy.
      Natural killer cell activity, which was low in the patients prior to therapy, was
      increased following administration of IFN alpha. In those patients with
      detectable platelet-associated autoantibody to gpIIb/IIIa, the amounts were
      reduced after treatment. Two patients had an unusually high percentage of T cells
      expressing the gamma delta T cell receptor, which decreased after therapy. The
      findings are consistent with an increase in Th 1 activity and a decrease in
      autoantibody production following IFN alpha therapy, which may be related to the
      beneficial effects of this cytokine.

PMID- 8986322
TI  - Experimental graft versus host disease in the (BN x LEW) F1 rat hybrid as a model
      for autoimmune disease. Study of early adenitis in lacrimal and salivary glands.
AB  - We analysed inflammatory changes at selected time intervals, of salivary and
      lacrimal glands in the developing immunostimulatory [BN-->(BN x LEW)F1] model of
      graft-versus-host (GVH) reaction. A focal mononuclear adenitis in lacrimal and
      salivary glands developed at day 7 and increased clearly in "onset"-rats.
      Inflammatory responses in submandibular and parotid glands were less consistent
      and weaker than in lacrimal glands. There was no significant focus score
      difference between males and females. The lacrimal infiltrates were characterised
      immunohistochemically with monoclonal antibodies. Our findings indicate that CD4+
      cells of donor origin dominated infiltrates, whereas a moderate number of B cells
      appeared only in large (late) foci. At stages corresponding to the onset of GVH
      disease (GVHD) in skin/labial mucosa, numerous CD8+ lymphocytes and NK cells were
      found in lacrimal glands, adjacent to ductal/ vascular plexa, sometimes forming
      small foci and with evidence of epithelial damage. We conclude that GVHD
      associated T cell migration into rat exocrine glands occurs as a result of the
      semi-alloantigen-activated phenotype properties of the T cells. This activation
      occurs initially in lymphoid tissue and migration into glands is secondary to
      this and unrelated to antigen specificity. We also found evidence of
      amplification and tissue damage, interpreted as due to local reactivation of the
      T cells.

PMID- 8986323
TI  - Environmental and experimental procedures leading to variations in the incidence
      of diabetes in the nonobese diabetic (NOD) mouse.
AB  - Environmental factors appear to be nongenetic risks of importance in the
      progression of insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes,
      whose mechanisms are not yet well understood. Stressful life events, in
      particular, have been linked to the expression of overt diabetes in humans.
      However, in rodent models of IDDM, contradictory data exist concerning the
      effects of stress on the disease. Here, we show that a stressor, such as long
      term repeated injections of vehicle (0.9% saline), was able to delay the
      appearance and/or decrease the incidence of diabetes in both sexes of NOD mice.
      Short-term chronic stress applied from the 6th to the 8th week of age by a
      combination of multiple stressors (overcrowding + immobilization + cold exposure
      + anesthesia) protected NOD mice from diabetes, particularly males. In contrast,
      prenatal stress, induced by immobilization of the mothers during the third part
      of pregnancy, accelerated the onset and increased the prevalence of diabetes at
      30 weeks of age in NOD females, while it had no effect in males. Finally,
      adrenalectomy appears to aggravate the development of diabetes in NOD mice,
      particularly in males. In conclusion, these data demonstrate that the appearance
      of diabetes in NOD mice is extremely sensitive to various experimental and
      environmental conditions. These results are discussed in the context of the
      complex neuroendocrine-immune interactions which occur during the progression of
      IDDM, with a particular focus on glucocorticoids and cytokines.

PMID- 8986324
TI  - Efficacy of low dose prednisone plus aspirin in preventing spontaneous abortions
      and/or fetal deaths due to antiphospholipid antibodies: results of a pilot study.

PMID- 8986325
TI  - Standardizing experiments with NOD mice.

PMID- 8986326
TI  - Ontogeny of place learning in children as measured in the radial arm maze, Morris
      search task, and open field task.
AB  - Children and adults were tested on 3 place learning tasks. Children under the age
      of 7 were inferior to older subjects in solving the tasks by using spatial
      relational solutions, but subjects of all ages were equally proficient in solving
      the task by using simple stimulus-reward associations (cued solutions). Accurate
      performance on the cued versions suggests that neither the general response
      demands nor the large size of testing environments rendered the tasks
      differentially inappropriate for young children. Instead, the nature of the
      cognitive demands were responsible for different levels of performance across the
      age groups. Because, in animal studies, spatial relational solutions but not cued
      solutions of these tests require mature and undamaged medial temporal lobe
      structures, the results suggest that these systems are not fully developed in
      humans before approximately 7 years of age.

PMID- 8986327
TI  - Associative learning in patients with cerebellar ataxia.
AB  - It has been claimed that patients with cerebellar pathology are impaired at
      associative learning. Patients with cerebellar ataxia (n = 7) were taught a
      visual-motor associative task. The task was chosen so as to allow comparisons
      with data currently being collected on the effects of cerebellar lesions on
      associative learning in monkeys. As a group the patients were as impaired at
      learning the task as a group of 8 patients with Huntington's disease. When each
      patient was individually matched with a control of the same age and IQ, some
      patients with cerebellar ataxia were found to be clearly impaired, but 2 were
      not. Of the 4 patients who were most clearly impaired, 2 had brainstem pathology
      and 2 did not. The relevance of these findings is discussed in relation to views
      concerning the functions of the cerebellum.

PMID- 8986328
TI  - Slow-wave activity in the spectral analysis of the electroencephalogram and
      volumes of hippocampus in subgroups of Alzheimer's disease patients.
AB  - This study examined patients who fulfilled the National Institute of Neurological
      and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders
      Association Work Group criteria for probable Alzheimer's disease (AD; n = 35) and
      controls for magnetic resonance imaging and psychometric data (n = 16) and for
      quantitative electroencephalogram data (n = 34). A cluster analysis performed on
      neuropsychological variables identified 2 AD subgroups: The AD1 group (n = 12)
      had impaired memory and executive functions but preserved verbal and visuospatial
      functions. The AD2 group (n = 23) had global impairment. The AD2 group had higher
      theta amplitude in the temporo-occipital, centroparietal, and frontal derivation
      and lower peak and mean frequency than the AD1 group or controls. Both AD groups
      had more severe memory deficits and clearly smaller hippocampal volumes than
      controls. This may implicate that the degree of damage in ascending activating
      systems differs in these subgroups, although the damage in the hippocampus is
      equal.

PMID- 8986329
TI  - A comparison of temporal decay in place memory tasks in rats (Rattus norvegicus)
      with lesions affecting thalamus, frontal cortex, or the hippocampal system.
AB  - Three experiments compared the effects of lesioning areas of thalamus, cortex,
      and the hippocampal system on delayed matching (DMTS) and nonmatching (DNMTS) to
      sample. Temporal decay was measured by comparing performances at different
      retention intervals (RIs) for rats trained to stability. Lesions of the lateral
      internal medullary lamina site in thalamus and the medial wall area in frontal
      cortex produced impairments that were significantly greater than for lesions of
      the mediodorsal nucleus in thalamus, the fornix, or the dorsal hippocampus. The
      effects of lesions on temporal decay differed depending on how RIs were
      manipulated. When RIs were manipulated within training sessions, the DMTS and
      DNMTS impairments were delay independent (i.e., none of the lesions increased the
      rate of temporal decay). When RIs were manipulated between sessions, thalamic
      lesions were associated with an increase in the rate of temporal decay of DNMTS.

PMID- 8986330
TI  - Role of the hippocampus plus subjacent cortex but not amygdala in visuomotor
      conditional learning in rhesus monkeys.
AB  - Rhesus monkeys were trained to learn a large series of visuomotor conditional
      associations, each involving the arbitrary coupling of a visual stimulus with 1
      of 3 potentially correct forelimb movements. The monkeys then received bilateral
      aspiration lesions of either the amygdala plus subjacent cortex or the
      hippocampus plus subjacent cortex. Hippocampal but not amygdala removals
      significantly retarded the learning of new visuomotor associations. Neither
      lesion affected retention. The findings argue against a general role for the
      amygdala in associating information across modalities, construed broadly to
      include motor information. By contrast, the finding that the hippocampal
      formation and its subjacent cortex play a role in learning new sensorimotor
      associations supports the view that this region participates in the long-term
      storage of associative information or in the recall of recently acquired
      information.

PMID- 8986331
TI  - Sex-related differences in cortical function after medial frontal lesions in
      rats.
AB  - The effects of sex on the performance of 4 spatial mazes (Morris water task,
      landmark task, radial arm maze, and egocentric radial arm maze) were studied in
      male and female rats given medial frontal lesions. Operated rats from both sexes
      were impaired at all of the tasks, but the frontal males were much less impaired
      than frontal females on the Morris task and the radial arm maze, both of which
      require animals to use multiple visual-spatial cues for their successful
      solution. Males also performed better on the egocentric maze. In contrast,
      frontal females performed better than frontal males at the landmark task, which
      is best solved by using a single spatial cue. The only sex difference in
      unoperated rats was a small advantage for females on the egocentric task. The sex
      differences may reflect an underlying difference in cortical organization or a
      differential response to cortical lesion in males and females.

PMID- 8986332
TI  - Prelimbic cortex specific lesions disrupt delayed-variable response tasks in the
      rat.
AB  - The role of the prelimbic cortex (PL) in rats was investigated with excitotoxic
      lesions. PL lesions altered the alternation scores in spontaneous and reinforced
      spatial delayed-alternation tasks. PL lesions induced a delay in conditioning
      under a temporal go/no-go alternation schedule but not under a continuous food
      reinforcement schedule in a runway. PL lesions had no effect on the acquisition
      of a standard radial-arm-maze task nor on a fixed-goal location task but
      disrupted the acquisition of a variable-goal location task in a radial-arm maze.
      The present results indicate that PL lesions replicated most of the behavioral
      deficits obtained with larger prefrontal lesions. PL lesions disrupted the
      acquisition of delayed-variable response tasks while leaving unaffected fixed
      response tasks. These results are discussed in relation with a working-memory, a
      response-selection, and an attentional hypothesis.

PMID- 8986333
TI  - A comparison of contextual and generalized auditory-cue fear conditioning:
      evidence for similar memory processes.
AB  - A number of variables influence contextual, but not auditory-cue, fear
      conditioning. However, several of these variables (isolation, stimulus
      preexposure, retention interval, and age) affect generalized auditory-cue fear.
      More generalized fear was found when (a) rats were isolated in a novel
      environment than when returned to their home cages, (b) the retention interval
      was 3 hr rather than 24 hr, and (c) in 18-day-old compared with 25-day-old rats.
      Moreover, preexposure to the auditory cue eliminated the isolation effect. At a
      behavioral-psychological level, these variables may exert their effects by
      influencing the processes that construct a memory representation of the stimulus.
      At a neural systems level, they may influence processing carried out in the
      thalamo-corticoamygdaloid auditory pathway.

PMID- 8986334
TI  - Sex differences in performance in the Morris water maze and the effects of
      initial nonstationary hidden platform training.
AB  - Sex differences in rats' performance on a stationary hidden-platform task
      (spatial task) in the Morris water maze and the effects of initial nonstationary
      hidden platform training (NSP training) were examined. The NSP training was
      designed to familiarize rats with the general requirements of the water-maze task
      without providing spatial information. NSP training led to faster acquisition and
      improved retention of the subsequent spatial task in both males and females.
      There was a sex difference favoring males on acquisition and retention of the
      spatial task only in rats that had not received previous NSP training. Moreover,
      there was an apparent reversed sex difference favoring females on some measures
      of spatial performance in NSP-trained rats. These results suggest that
      performance on the water-maze task, including the expression of sex differences,
      can be altered by previous familiarization with nonspatial aspects of the task.

PMID- 8986335
TI  - Chronic stress impairs rat spatial memory on the Y maze, and this effect is
      blocked by tianeptine pretreatment.
AB  - Chronic restraint stress causes significant dendritic atrophy of CA3 pyramidal
      neurons that reverts to baseline within a week. Therefore, the authors assessed
      the functional consequences of this atrophy quickly (within hours) using the Y
      maze. Experiments 1-3 demonstrated that rats relied on extrinsic, spatial cues
      located outside of the Y maze to determine arm location and that rats with
      hippocampal damage (through kainic acid, colchicine, or trimethyltin) had spatial
      memory impairments. After the Y maze was validated as a hippocampally relevant
      spatial task, Experiment 4 showed that chronic restraint stress impaired spatial
      memory performance on the Y maze when rats were tested the day after the last
      stress session and that tianeptine prevented the stress-induced spatial memory
      impairment. These data are consistent with the previously demonstrated ability of
      tianeptine to prevent chronic stress-induced atrophy of the CA3 dendrites.

PMID- 8986336
TI  - Both anteromedial and anteroventral thalamic lesions impair radial-maze learning
      in rats.
AB  - Disruption to the anterior thalamus (AT) may be an important factor in
      diencephalic amnesia. Rats with small lesions of the anteromedial (AM) or
      anteroventral (AV) nucleus showed persistent working-memory and reference-memory
      deficits in a 12-arm radial maze, although they were comparable to controls
      during the early part of training. The only activity difference in the maze was
      that lesioned rats failed to run more slowly when revisiting a baited arm. For
      all groups, both working and reference memory were impaired after extramaze cues
      were removed; removal of intramaze cues further impaired performance relative to
      the original conditions. These findings suggest the AT makes a distinct
      contribution to mnemonic functions, probably as part of an integrated system
      involving limbic cortex and the hippocampal formation, and that AT lesions
      produce a general rather than a specific deficit in spatial or working memory.

PMID- 8986337
TI  - Contribution of ventral tegmental area dopamine neurons to expression of
      conditional fear: effects of electrical stimulation, excitotoxin lesions, and
      quinpirole infusion on potentiated startle in rats.
AB  - Potentiated startle was used in this study to determine the fear-motivational
      functions of the ventral tegmental area (VTA). In Experiment 1, electrical
      stimulation of the VTA increased acoustic startle amplitudes. In subsequent
      experiments fear-potentiated startle was assessed following axon-sparing N-methyl
      D-aspartic acid (NMDA) lesions of the VTA and after bilateral intra-VTA infusion
      of the dopamine (DA) D2/3 receptor agonist quinpirole. The NMDA lesions produced
      substantial cell loss in the medial ventral tegmentum and suppressed fear
      expression. Similarly, inhibition of DA neuronal activity associated with locally
      administered quinpirole blocked fear-potentiated startle. It was suggested that
      VTA neurons and their forebrain DA projections regulate levels of aversive
      emotional arousal within the amygdala-based fear system.

PMID- 8986339
TI  - Mechanisms of Pavlovian conditioning: role of protection from habituation in
      spinal conditioning.
AB  - Conditioned antinociception can be established in spinal rats by pairing
      stimulation to one hind leg (the conditioned stimulus [CS]) with an intense
      tailshock (the unconditioned stimulus [US]). After this training, the paired CS
      (CS+) elicits greater antinociception on the tail-flick test than a CS that was
      explicitly unpaired (CS-). Five experiments are reported that suggest that this
      effect reflects protection from habituation. Experiment 1 showed that the CS
      (legshock) induces antinociception before training. Presenting the CS alone
      weakened (habituated) its antinociceptive impact (Experiment 2). Less habituation
      was observed when the CS was paired with the US (Experiment 3). Decreasing
      habituation to the CS- (by increasing the interval between trials) and
      facilitating habituation to the CS+ (by increasing the number of trials)
      effectively eliminated the CS+/CS- difference (Experiments 4 and 5).

PMID- 8986338
TI  - N-methyl-D-aspartate receptors in the basolateral amygdala are required for both
      acquisition and expression of conditional fear in rats.
AB  - Three experiments examined the effects of intra-amygdaloid infusions of an N
      methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate
      (APV), on contextual fear conditioning in rats. In Experiment 1, APV infusion
      into the basolateral amygdala (BLA), before training, disrupted the acquisition
      of contextual fear. In Experiment 2, APV produced a disruption of both the
      acquisition and expression of contextual fear. This blockade of contextual fear
      was not state dependent, not due to a shift in footshock sensitivity, and not the
      result of increased motor activity in APV-treated rats. In Experiment 3, fear
      conditioning was not affected by a posttraining APV infusion into the BLA. These
      results indicate that NMDA receptors in the BLA are necessary for both the
      acquisition and expression of Pavlovian fear conditioning to contextual cues in
      rats.

PMID- 8986340
TI  - Behavioral sensitization to cocaine, but not cocaine-conditioned behavior, is
      associated with increased dopamine occupation of its receptors in the nucleus
      accumbens.
AB  - Rats had repeated treatments with cocaine associated with a specific context
      (paired group). Evidence for classical conditioning of cocaine's motor-activity
      effects and context-specific behavioral sensitization to cocaine was obtained,
      relative to vehicle-treated (control) and pseudoconditioned (unpaired) groups.
      Only the paired group exhibiting context-specific behavioral sensitization had
      more dopamine bound to both D1-like and D2-like receptors in the nucleus
      accumbens than did rats in the control group receiving cocaine on the test day.
      No effects on receptor occupation were found in rats showing a classical
      conditioned response to a context previously paired with cocaine. Thus,
      sensitization to cocaine, but not classical conditioning of cocaine's behavioral
      effects, was associated with greater dopaminergic neurotransmission selectively
      in the nucleus accumbens.

PMID- 8986341
TI  - Sensitization to the psychomotor stimulant effects of amphetamine: modulation by
      associative learning.
AB  - The authors investigated the influence of associative pairing of contextual
      stimuli with amphetamine administration on the expression of psychomotor
      sensitization. Animals received d-amphetamine or saline in group-specific
      environments. Amphetamine produced robust behavioral sensitization in all
      environments, but when an amphetamine challenge was given in a test environment
      that was novel for some groups but not others, the expression of sensitization
      was completely context specific. An injection of saline in the amphetamine-paired
      environment produced a conditional response (CR), but this was quite small
      compared to the magnitude of the sensitized response, and sensitization remained
      completely context specific following extinction of the CR. Results are discussed
      in relation to 3 models of how context may modulate the expression of
      sensitization: an excitatory conditioning model, an inhibitory conditioning
      model, and an occasion-setting model.

PMID- 8986342
TI  - Developmental differences in place-learning performance between C57BL/6 and DBA/2
      mice parallel the ontogeny of hippocampal protein kinase C.
AB  - This study determined the ontogenic changes in learning and hippocampal protein
      kinase C (PKC) in C57 and DBA mice. Mice were tested on the visible- or hidden
      platform versions of the Morris water task starting at 17, 24, 31, or 60 days of
      age. Both strains learned to locate the visible platform at all ages. C57 mice
      learned to solve the hidden-platform task when they were 24 days old, whereas DBA
      mice never learned to solve this task. Using a [3H]-phorbol ester binding assay,
      the authors found that both strains had similar amounts of hippocampal PKC at 10
      and 17 days of age but that C57 mice had significantly more PKC at 24, 31, and 60
      days of age. Immunoblotting results revealed that C57 mice had more gamma-PKC,
      but not alpha-PKC, than DBA mice. Thus, the development of performance
      differences in spatial learning between C57 and DBA mice parallels the ontogeny
      of hippocampal PKC.

PMID- 8986343
TI  - 5-HT2 receptor involvement in conditioned olfactory learning in the neonate rat
      pup.
AB  - These experiments addressed the role of 5-HT2 receptors in conditioned olfactory
      learning. Ritanserin, a 5-HT2A/2C antagonist, was injected subcutaneously into
      postnatal day (PND) 7 pups before or after conditioned olfactory training to a
      peppermint odor. When the pups were tested for olfactory preference on PND 8,
      those injected with ritanserin before training failed to acquire an odor
      preference whereas those injected after training learned. This suggested that the
      5-HT2 receptor is required only in the acquisition of conditioned olfactory
      learning. Injection of ritanserin directly into the olfactory bulb before
      training also blocked preference for the peppermint odor. In pups that had
      depletion of the 5-HT input to the bulb, subcutaneous injection of a 5-HT2A/2C
      agonist was sufficient to maintain conditioned olfactory learning, confirming the
      importance of 5-HT in learning.

PMID- 8986344
TI  - Repeated isolation in the neonatal rat produces alterations in behavior and
      ventral striatal dopamine release in the juvenile after amphetamine challenge.
AB  - Rat pups were isolated from the mother and nest for 1 hr per day from Postnatal
      Day (PN) 2 to 9 At PN 27, rats were tested for behavioral responsiveness to 2.0
      or 7.5 mg/kg amphetamine. Only isolated rats receiving the 7.5 mg/kg dose
      displayed increased activity scores, compared with nonisolated and nonhandled
      controls. Their increased activity is attributed to a slower latency to enter
      into stereotypy. In a second experiment, similarly treated groups were challenged
      by the 7.5 mg/kg dose during a session in which a microdialysis probe implanted
      in the ventral striatum was being perfused. The challenge drug elicited a much
      greater increase in dialysate dopamine in isolated vs. nonisolated groups.
      Results are discussed with regard to dissociation between sensitized and
      subsensitized responses.

PMID- 8986345
TI  - Sound localization after kainic acid lesions of the dorsal nucleus of the lateral
      lemniscus in the albino rat.
AB  - The ability of rats to localize sounds in space was determined before and after
      kainic acid lesions of the dorsal nucleus of the lateral lemniscus (DNLL). The
      rats were trained to approach a 45-ms noise burst delivered from loudspeakers on
      the right or left of midline. Lesions were made by local injection of kainic acid
      into the DNLL. Rats with unilateral lesions of DNLL were impaired in their
      postoperative ability to localize a single noise burst. Rats with bilateral
      lesions also had deficits in postoperative performance, but the severity of the
      impairment was not substantially greater than that expected from a unilateral
      lesion. The mean pre- and postoperative minimum audible angles were 14.8 degrees
      and 40.4 degrees for rats with complete unilateral lesions and 13.5 degrees and
      36.0 degrees for rats with bilateral lesions.

PMID- 8986346
TI  - Combined glossopharyngeal and chorda tympani nerve transection elevates quinine
      detection thresholds in rats (Rattus norvegicus).
AB  - Using a conditioned shock avoidance procedure, behavioral quinine hydrochloride
      thresholds were measured before and after glossopharyngeal (GLX), chorda tympani
      (CTX), or combined glossopharyngeal and chorda tympani (GLX + CTX) transection,
      as well as after sham surgery. In Experiment 1, thresholds in the sham, CTX, and
      GLX rats (Rattus norvegicus) either improved (lowered) or remained the same after
      surgery. In Experiment 2, GLX + CTX caused a pronounced 1.5 log10 unit increase
      in presurgically measured thresholds. Neither the glossopharyngeal nor the chorda
      tympani nerve is necessary for normal sensitivity to low quinine concentrations
      provided the other is intact. When both of these nerve are transected, however,
      the remaining afferent input is not sufficient to maintain normal detection
      performance.

PMID- 8986347
TI  - Prenatal alcohol and stress interact to attenuate ejaculatory behavior, but not
      serum testosterone or LH in adult male rats.
AB  - Restraint stress reduced blood alcohol levels in pregnant rats given a liquid
      alcohol diet. The male offspring prenatally exposed to both stress and alcohol
      failed to ejaculate spontaneously, although they copulated normally following
      exogenous testosterone (T) administration. Males prenatally exposed only to
      alcohol or only to stress showed no behavioral deficits. Adult serum T and
      luteinizing hormone levels were normal in both of the fetal alcohol exposed male
      groups. It appears that the androgen threshold for ejaculatory behavior is
      elevated in males prenatally exposed to alcohol plus stress and cannot be
      realized with normal testosterone titers, but it can be attained with exogenous
      hormone administration. Presumably the alcohol and stress combination interfered
      with ontogenetic patterns of T needed to fully masculinize the fetal nervous
      system.

PMID- 8986348
TI  - Comparison of the effects of 17 alpha-methyltestosterone, methandrostenolone, and
      nandrolone decanoate on the sexual behavior of castrated male rats.
AB  - In a series of 3 experiments, adult male Long-Evans rats were castrated and
      treated with 1 of 3 different anabolic-androgenic steroid (AAS) compounds (17
      alpha-methyltestosterone, methandrostenolone, or nandrolone decanoate) for 6
      weeks. In each experiment, subjects received daily injections of a high, medium,
      or low dose of AAS or the oil vehicle. The AAS effects on body weight in
      gonadectomized male rats were modest, and no effects on locomotor activity were
      observed. The AAS compounds administered at doses comparable with human abuse
      levels were not equipotent in maintaining male sexual behavior patterns
      (nandrolone decanoate > methandrostenolone > 17 alpha-methyltestosterone). In
      addition, the behavioral actions of AAS compounds did not parallel stimulation of
      sexual accessory glands. The authors reported that this study is the first to
      quantify the dose-response characteristics of individual AAS compounds with
      regard to these behavioral and endocrine measures.

PMID- 8986349
TI  - Effects of MK-801 on spatial memory in homing and nonhoming pigeon breeds.
AB  - Homing pigeon breeds, the product of artificial selection on the basis of
      navigational and spatial ability, differ from nonhoming breeds in hippocampal
      size and distribution of N-methyl-D-aspartate (NMDA) dependent receptors. The
      effects of MK-801 (0.1 mg/kg administered intraperitoneally), a noncompetitive
      NMDA antagonist, on spatial reference memory (RM) were compared between the 2
      breeds in a radial arm maze task. MK-801 disrupted the acquisition of RM in the
      nonhoming group but not the homing group, which was equivalent to the 2 saline
      only control groups. As in previous findings with mammals, working memory was not
      affected by MK-801. This behavioral dissociation, coupled with differences in
      NMDA-dependent long-term potentiation between breeds, suggests an exceptional
      opportunity to investigate the role and function of the dorsomedial telencephalon
      region in spatial RM, through anatomical, neurochemical, and behavioral
      comparisons between homing and nonhoming pigeon breeds.

PMID- 8986350
TI  - A small amount of wheel running facilitates eating in nondeprived rats.
AB  - A high level of dopaminergic activation such as that produced by a high dose of
      amphetamine suppresses eating, whereas a low level such as that produced by a low
      dose can have the opposite effect. Like a high dose of amphetamine, a high level
      of wheel running also suppresses eating. It was hypothesized that this
      suppression is due to dopaminergic activation produced by wheel running. If so, a
      relatively small amount of wheel running should produce a low level of
      dopaminergic activation and thus have the same effect as a low dose of
      amphetamine: facilitation of eating. In the present experiment, nondeprived rats
      were allowed to run in a wheel for 30 min before a feeding test. As predicted, a
      little wheel running facilitated eating in these rats relative to appropriate
      controls. The present results may be relevant to an understanding of eating
      disorders in humans.

PMID- 8986351
TI  - Lesions of the lateral parabrachial nucleus block the aversive motivational
      effects of both morphine and morphine withdrawal but spare morphine's
      discriminative properties.
AB  - This study examined if the aversive properties of morphine, the aversive
      properties of morphine withdrawal, and the discriminative properties of morphine
      are mediated by common neurobiological substrates. Lesions of the lateral
      parabrachial nucleus, which blocked the aversive properties of morphine in the
      conditioned taste aversion paradigm, also blocked the acquisition of conditioned
      place aversions to environments paired with the aversive properties of morphine
      withdrawal in morphine-dependent rats. When morphine and saline were used as cues
      in a discrimination task, however, both sham-operated and lesioned rats were able
      to solve the task.

PMID- 8986352
TI  - Applications of NMR imaging to the time-dependent swelling effect in polymers.
AB  - The swelling process is often observed in many polymers of interest and is an
      important phenomenon for the understanding of many biopolymers. This important
      process, however, is known as poorly understood in the area in polymer science.
      One of the reasons is that the conventional method of examining the swelling
      process is often inconsistent. Since it has many important properties including
      non-invasiveness, Nuclear Magnetic Resonance (NMR) Micro-imaging has become a
      significant method of analyzing biomaterials as well as biological specimens
      [1,2]. In the present study, a time-dependent swelling process was observed non
      invasively to investigate the polymeric swelling effect using NMR micro-imaging.
      The present study provides a noble and non-invasive method of measuring the
      degree of swelling as well as volumetric changes occurring in polymers immersed
      in liquid. The information obtained relates to both a water ingress process and
      volumetric changes of polymer specimens. This proposed method also will provide
      more reliable techniques to ascertain the time-dependent swelling process than
      the other conventional methods. One of the important aspects of the present study
      is that the proposed method is a non-invasive technique and is also capable of
      ascertaining the time-dependent process of the swelling. This may be a new method
      of measuring the degree of swelling as well as the time-dependent water ingress
      process in a polymer.

PMID- 8986353
TI  - Radiation effects on polypropylene for sterilization.
AB  - In order to improve the resistance of gamma-radiation sterilization of
      polypropylene (PP), the formulations of the additives such as antioxidants,
      crosslinking agent, and trans-stilbene oxide (StO) have been carried out. The
      irradiated PP and ethylene-propylene copolymer samples with control and additives
      were characterized by mechanical tester, colorimetry, and Fourier transform
      infrared spectroscopy with total attenuated reflectance mode (FTIR-ATR).
      Crosslinking agent and StO formulated PP showed remarkable radiation resistance
      and minimum discoloration. Also, radiation resistance of ethylene-propylene
      copolymers with 3% of ethylene contents was better than that of PP homopolymers
      in the case of no additives. The proposed mechanisms of radiation stabilization
      with additives are also discussed.

PMID- 8986354
TI  - Improved bonding strength of polyethylene/polymethylmetacrylate bone cement--a
      preliminary study.
AB  - The adhesion of polymethylmetacrylate (PMMA) bone cement and low density
      polyethylene (LDPE) substrate by means of corona discharge treatment are
      presented. The surfaces were characterized by water contact angle goniometer,
      Fourier-transform infrared spectroscopy in the attenuated total reflectance mode
      (FTIR-ATR), electron spectroscopy for chemical analysis (ESCA), and scanning
      electron microscopy (SEM) for surface morphology. The bonding strength between
      bone cement and LDPE with varying intensity of corona treatment was evaluated by
      a 180 degrees peel test. The water contact angles decreased with increasing
      treatment intensity from 95.0 +/- 1.8 to around 43.5 degrees. It was observed
      that the oxygen containing groups as hydroxyl, ether, carboxylic acid, ester,
      ketone or aldehyde groups were introduced on the LDPE surfaces by corona
      treatment. The peel strength steeply increased from 0 to 1.75 kgf/cm with
      increasing the intensity of corona treatment. The improved adhesion of bone
      cement onto LDPE substrate may be due to only secondary force such as hydrogen
      bonding between PMMA bone cement and hydrophilized LDPE substrate.

PMID- 8986355
TI  - Self-setting hydroxyapatite cement as a carrier for bone-forming cells.
AB  - To investigate the feasibility of using self-setting hydroxyapatite cement as a
      carrier for marrow cells having a high osteogenic ability, a porous form of this
      cement was fabricated and combined with cultured marrow cells. Marrow cells were
      obtained from the femurs of a seven-week-old male Fischer 344 rat and cultured in
      Eagle's MEM containing 15% fetal bovine serum for ten days before being combined
      with the porous cement or with Interpore 200 hydroxyapatite as a control. The
      composites were subcutaneously implanted into syngeneic rats and harvested after
      six weeks. In both types of implants, active osteoblasts together with bone
      formation were detected in contact with the pore surfaces. No cartilage formation
      was observed in any of the pores. Both types of implants with and without marrow
      cells caused very little foreign body reaction. These results indicate that self
      setting hydroxyapatite cement containing marrow cells possesses a high osteogenic
      ability and may be useful as a bone graft substitute as well as a novel delivery
      system for bone-forming cells.

PMID- 8986356
TI  - The elbow joint and its total arthroplasty. Part I. A state-of-the-art review.
AB  - Various pathologies, notably rheumatoid arthritis and/or trauma, are all known to
      cause severe pain and/or reduction of functional motion at the elbow joint.
      Implantation of a total arthroplasty, in such cases, has emerged as the first
      choice for management. For acceptable clinical performance, such an arthroplasty
      should be designed fully cognizant of various germane aspects of the anatomy,
      kinesiology and biomechanics of the normal joint. These aspects, together with a
      critical appraisal of the different classes of arthroplasty designs and a
      discussion of areas for further research (aimed at improving the in vivo
      performance of the prosthesis), are the subjects of the present review.

PMID- 8986357
TI  - The elbow joint and its total arthroplasty. Part II. Finite element study.
AB  - The stresses in various sections of two-dimensional models of the elbow joint,
      without and with a prosthesis (the humeral component of a total elbow
      prosthesis), were obtained using the finite element analysis method. Three
      parameters were varied: type of applied load; method of fixation of the
      prosthesis to the contiguous bone; and shape of the head of the prosthesis. The
      results are discussed with particular reference to stress shielding and overload
      in the cortical and cancellous bones, respectively, and a qualitative comparison
      between the present values and those given by previous workers who used three
      dimensional models. Comments are made regarding the clinical implications of the
      results.

PMID- 8986358
TI  - Ion implantation and thermal nitridation of biocompatible titanium.
AB  - Nitrogen implantation and thermal nitridation processes are investigated to
      improve the wear resistance of titanium medical devices. Ion implantation uses 80
      keV nitrogen ions and doses ranging between 1 x 10(17) and 5 x 10(17)/cm2 to
      modify the surface layers up to 140 nm depth. Stable surface layers are obtained
      at high ion doses by post-annealing at 550 degrees C for 30 min. Thermal
      processes are developed as a function of the time (20-90 min) and annealing
      temperature (950-1100 degrees C) in a dry nitrogen atmosphere. The amount of
      titanium nitride formed during the thermal process increases with the annealing
      temperature and time. Samples are analysed by Rutherford Backscattering
      Spectroscopy (RBS), Auger Electron Spectroscopy (AES) and Scanning Electron
      Microscopy (SEM). Ion implantation and thermal nitridation processes increase the
      surface hardness and wear resistance improving the mechanical properties of
      titanium used for movable devices for total joint replacements, such as the hip
      and knee protheses.

PMID- 8986359
TI  - Activation-dependent and biphasic electromagnetic field effects: model based on
      cooperative enzyme kinetics in cellular signaling.
AB  - Experiments on filed exposure effects of extremely-low-frequency electric and
      magnetic fields (EMFs) on biological systems have shown that, in many cases, the
      biological-functional status is of fundamental importance for an effective
      interaction. For example, studies of calcium uptake regulation in cells of the
      immune system, particularly in T lymphocytes, have revealed that, depending on
      the degree of cellular activation, either stimulatory, inhibitory, or no field
      exposure effects are observed for identical field parameters. A brief summary of
      the experimental findings is given, and a theoretical approach is presented that
      accounts in a qualitative manner for EMF exposure effects 1) that depend on the
      degree of cellular activation and 2) that exhibit a biphasic response behavior
      (stimulation/ inhibition). In the model, biochemical stimulation of the cell
      results in activation of specific signaling pathways that regulate calcium
      dynamics in the cell (calcium release from intracellular calcium stores and
      capacitative calcium entry). We assume that, controlled by these pathways, a
      specific EMF-sensitive enzyme system becomes activated. The activated enzyme, in
      turn, exhibits a feedback control on the signal processes, thus leading to a
      modulation of calcium entry. This modulation may affect other cellular processes
      that are calcium dependent (e.g., DNA synthesis). Magnetic field exposure is
      assumed to alter the kinetics of a specific step within the enzyme-reaction cycle
      in accord with the radical-pair mechanism, although the formulism is not
      restricted to this specific example. Results show that inclusion of cooperative
      steps within the enzyme-reaction cycle provides a theoretical basis that enables
      a simple description of a biphasic response behavior to EMF exposure.

PMID- 8986360
TI  - Coronary heart diseases: assessment of risk associated with work exposure to
      ultralow-frequency magnetic fields.
AB  - The present analysis was stimulated by previous findings on the possible
      influence of natural ultralow-frequency (ULF; 0.001-10 Hz) geomagnetic field
      variations on the cardiovascular system and indications of an effect of man-made
      ULF magnetic fields on the rate of myocardial infarction. In the present study,
      we considered the occupational health hazards of the strongest ULF magnetic
      fields in densely populated urban areas. Measurements of ULF magnetic field
      fluctuations produced by trains powered by DC electricity were performed by means
      of a computer-based, highly sensitive, three-component magnetometer. We found
      that the magnitude of magnetic field pulses inside the driver's cab of electric
      locomotives (ELs) could be > or = 280 microT in the horizontal component
      perpendicular to the rails and up to approximately 130 microT in the vertical
      component, and, in the driver's compartment of electric motor unit (EMU) trains,
      they were approximately 50 and 35 microT, respectively. We have investigated the
      relationships between the occupational exposure to ULF magnetic field
      fluctuations produced by electric trains and cardiovascular diseases (CVDs) among
      railroad workers in the former Soviet Union. We have analyzed medical statistical
      data for a period of 3 years for approximately 45,000 railroad workers and 4,000
      engine drivers. We have also analyzed 3 years of morbidity data for three
      subgroups of engine drivers (approximately 4,000 in each group) operating
      different types of trains. We find that EL drivers have a twofold increase in
      risk (2.00 +/- 0.27) of coronary heart diseases (CHDs) compared with EMU drivers.
      Because our analysis of major CVDs shows that the examined subpopulations of
      drivers can be considered to have had equal exposure to all known risk factors,
      the elevated CHD risk among EL drivers could be attributed to the increased
      occupational exposure to ULF magnetic fields.

PMID- 8986361
TI  - Conductivity of a chronic wound model.
AB  - The dermal equivalent matrix (DEM) is well recognized as an in vitro model of
      wound healing. To quantify the low-frequency (10-100 Hz) electric fields that
      cause proliferative effects in this model, determination of conductivity is a
      prerequisite. This article outlines a four-electrode technique to establish
      conductivity of DEM at 100 Hz. DEM is fabricated from human foreskin fibroblasts
      and collagen type I extracted from rat tail. Over 8-10 days, fibroblasts contract
      translucent collagen matrices into opaque circular "dime-sized" structures that
      are approximately 10 mm in diameter and 1 mm thick. To determine conductivity,
      rectangular samples are cut from each matrix. Thickness and width of each sample
      is measured by microscopy. Over 17 experiments, conductivity of multiple samples
      is found to be related inversely to cell density in matrix, with 1.22
      Siemens/meter (S/m) corresponding to 0 cells/mm3 matrix and 0.78 S/m
      corresponding to 2.6 x 10(4)cells/mm3. These results are consistent with a
      physical model of DEM consisting of pores within a framework of type I collagen;
      the cells and medium are within the pores. The model is most compatible with a
      relative pore area of 73% and a cell volume of 9.0 x 10(-6)mm3 (the latter in
      agreement with published fibroblast dimensions). From these results, DEM is much
      more porous than dermis. Although DEM has been recognized as a reasonable model
      of chronic wound healing, this dissimilarity is noted.

PMID- 8986362
TI  - Electric fields and proliferation in a chronic wound model.
AB  - A wound model for decubitus and leg ulcers consisting of human dermal fibroblasts
      in type I collagen dermal "equivalent" matrix (DEM) was exposed in vitro to
      electric fields similar to postulated endogenous fields in wounds. After an 8-10
      day maturation period, conductivity of DEM samples was determined. Then, DEM
      samples were mounted in oval windows equidistant between Ag/AgCl agar electrodes
      in exposure chambers containing serum-free medium. A known low-frequency
      sinusoidal current was then applied for 12 h, and the average electric field
      amplitude was calculated in the region of the cells. After a 6 h hiatus, 3H
      thymidine was introduced for 6 h. This was followed by assay. Over a series of
      trials, field amplitude ranged from 18 to 1,000 mV/m at frequencies of 10 and 100
      Hz. Proliferation was measured by total DNA and 3H-thymidine incorporation.
      Results indicated that a narrow amplitude window between 37 and 50 mV/meter at 10
      Hz yielded increases in proliferation: At maximum (41 mV/m), there was a 70%
      increase in total DNA (P < .01). Increases occurred in 3H-thymidine incorporation
      at 41-50 mV/m but not at other amplitudes (P < .05). Increases in total DNA at 41
      mV/m occurred at 10 Hz but not 100 Hz (P < .01). 3H-thymidine incorporation was
      in agreement (P < .05). Response was also a function of cell density within
      matrix. Proliferation occurred in the same amplitude and frequency ranges in
      which endogenous fields are expected to occur.

PMID- 8986363
TI  - Conductivities of pig dermis and subcutaneous fat measured with rectangular pulse
      electrical current.
AB  - We examined experimentally the relationship between perpendicular and tangential
      electrical conductivities, sigma, and peak current density J, in pig skin dermis
      and subcutaneous fat specimens by using a four-electrode measuring system with
      rectangular pulse electrical current (RPEC). We also investigated the
      relationship of the conductivity, sigma, vs. pulse rate, f. The rates were
      selected at 8, 32, 64, and 128 pulses per second (pps), and the pulse width was
      fixed at 140 microseconds. These values are often used in vivo to enhance
      cutaneous regeneration with RPEC stimulation. It was found that the
      conductivities may be approximated to be [equation: see text] for the skin dermis
      and [equation: see text] for the subcutaneous fat in the conditions of this
      experiment. These findings implies that the conductivities of pig skin dermis and
      subcutaneous fat are anisotropic, i.e., sigma x = sigma y not equal to sigma z.
      It was also found that the conductivities are independent of current density and
      pulse rate in the current range from 20 microA/cm2 to 120 mA/cm2.

PMID- 8986364
TI  - Weak extremely-low-frequency magnetic field-induced regeneration anomalies in the
      planarian Dugesia tigrina.
AB  - We recently reported that cephalic regeneration in the planarian Dugesia tigrina
      was significantly delayed in populations exposed continuously to combined
      parallel DC and AC magnetic fields. This effect was consistent with hypotheses
      suggesting an underlying resonance phenomenon. We report here, in a parallel
      series of investigations on the same model system, that the incidence of
      regeneration anomalies presenting as tumor-like protuberances also increases
      significantly (P < .001) in association with exposure to weak 60 Hz magnetic
      fields, with peak intensities ranging between 1.0 and 80.0 microT. These
      anomalies often culminate in the complete disaggregation of the organism. Similar
      to regeneration rate effects, the incidence of regeneration anomalies is
      specifically dependent upon the planaria possessing a fixed orientation with
      respect to the applied magnetic field vectors. However, unlike the regeneration
      rate effects, the AC magnetic field alone, in the absence of any measurable DC
      field, is capable of producing these anomalies. Moreover, the incidence of
      regeneration anomalies follows a clear dose-response relationship as a function
      of AC magnetic field intensity, with the threshold for induced electric field
      intensity estimated at 5 microV/m. The addition of either 51.1 or 78.4 microT DC
      magnetic fields, applied in parallel combination with the AC field, enhances the
      appearance of anomalies relative to the 60 Hz AC field alone, but only at certain
      AC field intensities. Thus, whereas our previous study of regeneration rate
      effects appeared to involve exclusively resonance interactions, the regeneration
      anomalies reported here appear to result primarily from Faraday induction
      coupling. These results together with those reported previously point to two
      distinct physiological effects produced in regenerating planaria by exposure to
      weak extremely-low-frequency (ELF) magnetic fields. They further suggest that the
      planarian, which has recently been identified elsewhere as an excellent system
      for use in teratogenic investigations involving chemical teratogens, might be
      used similarly in teratogenic investigations involving ELF magnetic fields.

PMID- 8986365
TI  - Characterizing cellular systems by means of dielectric spectroscopy.
AB  - The dielectric behavior of a suspension of synchronized, spherical cells has been
      investigated in relation to the electrical parameters of certain cell structures.
      In the quasistatic approximation, Poisson's equations are solved for the
      respective diffusive media, and the local charge distributions are derived by
      taking into account the continuity equations. The results describe both alpha and
      beta dispersion and reduce, in the corresponding limiting cases, to previous
      reports. The dependence of suspension permittivity in alpha- and beta-dispersion
      ranges on the diffusive effects, the conductivity, and the permittivity of
      cytoplasm, of membrane, and of culture medium as well as on membrane thickness is
      pointed out. The possibility is pointed out of characterizing cellular behavior
      by means of the evolution of certain electrical and morphological parameters
      during cell cycle progression as well the effects of different stimuli on
      cellular systems derived by fast dielectric spectroscopy.

PMID- 8986366
TI  - Numerical and experimental dosimetry of Petri dish exposure setups.
AB  - Crawford TEM cells are often used to expose cell cultures or small animals in
      order to study the effects caused by high-frequency fields. They are self
      contained, easy-to-use setups that provide a rather homogeneous field
      distribution in a large area around its center, corresponding approximately to
      far-field conditions. However, a number of conditions must be met if such TEM
      cells are intended to be used for in vitro experiments. For instance, poor
      interaction with the incident field must be maintained to avoid significant field
      disturbances in the TEM cell. This is best achieved with E-polarization, i.e.,
      when the E-field vector is normal to the investigated cell layer lining the
      bottom of a synthetic Petri dish. In addition, E-polarization provides the most
      homogeneous field distribution of all polarizations within the entire layer of
      cells. In this paper, we present a detailed dosimetric assessment for 60 and 100
      mm Petri dishes as well as for a 48-well titer plate at 835 MHz. The dosimetry
      was performed by using numerical computations. The modeling and the
      simplifications are validated by a second numerical technique and by experimental
      measurements. For thin liquid layers, an approximation formula is provided with
      which the induced field strength for many other experiments conducted in Petri
      dishes can be assessed reliably.

PMID- 8986367
TI  - Spatial learning deficit in the rat after exposure to a 60 Hz magnetic field.
AB  - Rats were trained in ten daily sessions to perform in a 12-arm radial maze, which
      is a behavioral test for spatial memory functions. Exposure to a 60 Hz magnetic
      field (45 min, 0.75 mT) immediately before each training session retarded
      learning significantly. Pretreatment with the cholinergic agonist physostigmine
      before magnetic field exposure reversed the field's effect on spatial learning.
      Data from this experiment indicate that magnetic field-induced spatial learning
      deficit is caused by the effect of the field on cholinergic systems.

PMID- 8986368
TI  - Effect of continuous-wave and amplitude-modulated 2.45 GHz microwave radiation on
      the liver and brain aminoacyl-transfer RNA synthetases of in utero exposed mice.
AB  - Investigations have been carried out concerning the effects of microwave (MW)
      exposure on the aminoacyl-transfer ribonucleic acid (tRNA) synthetase of the
      progeny of females that were exposed during their entire period of gestation (19
      days). The changes caused by continuous-wave (CW) and amplitude-modulated (AM) MW
      radiation have been compared. CFLP mice were exposed to MW radiation for 100 min
      each day in an anechoic room. The MW frequency was 2.45 GHz, and the amplitude
      modulation had a 50 Hz rectangular waveform (on/off ratio, 50/50%). The average
      power density exposure was 3 mW/cm2, and the whole body specific absorption rate
      (SAR) was 4.23 +/- 0.63 W/kg. The weight and mortality of the progeny were
      followed until postnatal day 24. Aminoacyl-tRNA synthetase enzymes and tRNA from
      the brains and livers of the offspring (461 exposed, 487 control) were isolated.
      The aminoacyl-tRNA synthetase activities were determined. The postnatal increase
      of body weight and organ weight was not influenced by the prenatal MW radiation.
      The activity of enzyme isolated from the brain showed a significant decrease
      after CW MW exposure, but the changes were not significant after 50 Hz AM MW
      exposure. The activity of the enzyme isolated from liver increased under CW and
      50 Hz modulated MW.

PMID- 8986369
TI  - Protein kinase C activity is altered in HL60 cells exposed to 60 Hz AC electric
      fields.
AB  - We examined the effects of electric fields (EFs) on the activity and subcellular
      distribution of protein kinase C (PKC) of living HL60 cells. Sixty Hertz AC
      sinusoidal EFs (1.5-1,000 mV/cm p-p) were applied for 1 h to cells (10(7)/ml) in
      Teflon chambers at 37 degrees C in the presence or absence of 2 microM phorbol 12
      myristate 13-acetate (PMA). PMA stimulation alone evoked intracellular
      translocation of PKC from the cytosolic to particulate fractions. In cells that
      were exposed to EFs (100-1,000 mV/cm) without PMA, a loss of PKC activity from
      the cytosol, but no concomitant rise in particulate PKC activity, was observed.
      In the presence of PMA, EFs (33-330 mV/cm) also accentuated the expected loss of
      PKC activity from the cytosol and augmented the rise in PKC activity in the
      particulate fraction. These data show that EFs alone or combined with PMA promote
      down-regulation of cytosolic PKC activity similar to that evoked by mitogens and
      tumor promoters but that it does not elicit the concomitant rise in particulate
      activity seen with those agents.

PMID- 8986370
TI  - Measurements described in a paper by Blackman, Blanchard, Benane, and House are
      statistically invalid.
AB  - Blackman et al. [1994] describe an experiment that purports to show that weak 45
      Hz magnetic fields inhibit the growth of neurites from PC-12 cells treated with a
      growth stimulation factor. I present a statistical analysis of the data in that
      paper that shows that the data were corrupted in some way; hence, the results are
      invalid.

PMID- 8986371
TI  - Mechanical vibration in "double-wound" magnetic field exposure coils.
AB  - It has been suggested that "double-wound" (bifilar) exposure coils are capable of
      producing a sham environment in which hum and vibration will be "similar" to the
      field-exposed condition. We found by direct measurements in a bifilar coil system
      that vibration amplitude in sham and exposed conditions differed by a factor of
      50 when our test system was driven at B = 10 mT. We also found that the normal
      laboratory environment can include vibrations of an intensity similar to that
      produced by the exposure system, although not necessarily of similar spectral
      distribution.

PMID- 8986372
TI  - No effect of exposure to static and sinusoidal magnetic fields on nitric oxide
      production by macrophages.
AB  - The effects of exposure to static (1 - 100 mT) or sinusoidal (1 Hz, 1.6 mT)
      magnetic fields on the production of nitric oxide (NO) by murine BCG-activated
      macrophages were investigated. In these cells, the inducible isoform of NO
      synthase is present. No significant differences were observed in nitrite levels
      among exposed, sham-exposed, or control macrophages after exposure for 14 h to
      static fields of 1, 10, 50, and 100 mT and to sinusoidal 1.6 mT, 1 Hz magnetic
      fields.

PMID- 8986373
TI  - Microtubule assembly in clarified Xenopus egg extracts.
AB  - Crude cytoplasmic extracts made from Xenopus eggs have proven to be uniquely
      useful in the studies of the mechanism of spindle microtubule assembly dynamics
      and chromosome movement during progression through the cell cycle. We examined
      microtubule dynamic instability in the Xenopus system using video-enhanced
      differential interference contrast microscopy (VE-DIC), which required high-speed
      centrifugation in order to clarify crude Xenopus extracts of refractile
      particles. Surprisingly, the resultant clarified, undiluted extracts exhibited
      virtually no microtubule catastrophe, even in the presence of high MPF (cyclin
      B/p34cdc2 kinase) activity and mitogen-activated protein (MAP) kinase activity, a
      down-stream kinase also implicated in regulating microtubule dynamics.
      Microtubule elongation occurred at plus ends, and interphase microtubules grew at
      17-30 microns/min while metaphase [meiotic, myelin basic protein kinase activity
      which is diagnostic for cytostatic factor (CSF)-arrested] microtubules grew at
      about 10 microns/min. Plus-end shortening rates for both interphase and metaphase
      extracts were > 50 microns/min. Addition of okadaic acid, a protein phosphatase
      inhibitor known to activate MAP kinase activity and cause an increase in
      microtubule turnover in extracts made from sea urchin eggs, had no effect on
      microtubule catastrophe in either interphase or metaphase Xenopus extracts. In
      addition, the microtubules assembled in interphase extracts were less sensitive
      to dilution than those in metaphase. This study is the first to describe the
      dynamic instability of microtubules in Xenopus extracts without the addition of
      exogenous tubulins or other buffer contaminants.

PMID- 8986374
TI  - Structure and cytoskeletal organization of migratory mesoderm cells from the
      Xenopus gastrula.
AB  - Prospective mesoderm cells from the Xenopus gastrula exhibit interesting motile
      behavior, e.g., a transition from a nonmigratory state to an active translocation
      that can be induced experimentally, and directional substrate-guided locomotion.
      We examine the cytoskeletal organization of these embryonic cells. We show that
      the large, globular cells are enclosed in a triple shell consisting of an
      actomyosin cortex, a peripheral cytokeratin layer, and a peculiar microtubule
      basket that surrounds the cell body and constrains the distribution of large
      inclusions such as yolk platelets. Consistent with the migratory phenotype of
      these cells, no stress fibers or focal contacts are present. Mesoderm cells
      possess typical lamellipodia with fine protruding filopodia. The leading edge of
      the lamellar part exposes binding sites for the fodrin SH3 domain. Lamellipodia
      are connected to the cell body through actin filament bundles of the upper cell
      cortex. Myosin II is present in the cell body and extends to varying degrees into
      lamellipodia. We present indirect evidence that myosin II is located in the upper
      part of lamellipodia and propose a model that involves myosin II in a dynamic
      linkage between lamellipodium and the cortex of the cell body.

PMID- 8986375
TI  - Dynamics of filamentous actin organization in the sea urchin egg cortex during
      early cleavage divisions: implications for the mechanism of cytokinesis.
AB  - We have used confocal laser scanning microscopy in conjunction with BODIPY
      phallacidin staining of filamentous actin to investigate changes in the quantity
      and organization of cortical actin during the first two cell cycles following
      fertilization in eggs of the sea urchin Strongylocentrotus purpuratus.
      Quantification of fluorescent phallacidin staining reveals that the amount of
      filamentous actin (F-actin) in the cortex undergoes cyclical increases and
      decreases during early cleavage divisions, peaking near the beginning of the cell
      cycle and decreasing to a minimum at cytokinesis. Changes in the content of
      cortical F-actin are accompanied by the growth and disappearance of rootlet-like
      bundles of actin filaments which extend from the bases of microvilli that cover
      the surface of the egg. Actin rootlets reach their maximum degree of development
      by 20 min postfertilization, and then gradually decrease in number and length
      over the next 40 min. Small actin rootlets persist until cleavage, disappear
      during cytokinesis, and reform following division. The formation of actin
      rootlets requires cytoplasmic alkalization and is inhibited by cytochalasin D.
      Cytochalasin D washout experiments demonstrate that assembly of the cortical
      actin cytoskeleton can be blocked until 5 min before the onset of cleavage and
      still allow normal cytokinesis. These results illustrate the dynamic nature of
      cortical actin organization during early development and demonstrate that
      cytokinesis occurs at the point of minimum cortical F-actin content. They further
      demonstrate that cytokinesis can occur in embryos in which the normal
      developmental sequence of changes in cortical actin organization has been blocked
      by treatment with cytochalasin D, suggesting that these changes do not function
      in the establishment of the contractile apparatus for cytokinesis, but rather
      serve other developmental functions. Cell Motil. Cytoskeleton 36:30-42, 1997.

PMID- 8986376
TI  - Ultrastructure and cell-cell coupling of cardiac myocytes differentiating in
      embryonic stem cell cultures.
AB  - Differentiation cultures of embryonic stem (ES) cells can be a useful in vitro
      system for understanding cardiac myocyte development. However, cell morphometry,
      sarcomere development, and functional cell-cell junction formation have not been
      examined in detail to determine whether ES cell-derived cardiac myocytes exhibit
      structural and functional characteristics similar to cardiac myocytes within the
      developing heart. Therefore, we examined cellular dimensions, sarcomere
      formation, and cell-cell contacts in differentiating cardiac myocytes derived
      from mouse D3-ES cell cultures. Cells exhibited rod-shaped morphology and had
      single centrally located nuclei, typical of maturing cardiac myocytes. The
      cellular dimensions of 59 individual cardiac myocytes within contracting foci of
      ES cell cultures were analyzed (length = 42.2 +/- 2.1 microns, area = 197 +/- 19
      microns2, and diameter = 5.5 +/- 0.3 microns) and found to be similar to myocytes
      in vivo. Transmission electron micrographs of ES cell-derived cardiac myocytes
      indicated myofibrillar architecture ranged from sparse and disorganized to
      densely packed, parallel arrays of myofibrils organized into mature sarcomeres.
      This pattern of myofibrillar assembly in maturing sarcomeres was similar to that
      observed during in vivo myocyte differentiation. Another hallmark of cardiac
      development is the formation of intercalated discs, which functionally couple
      adjacent cardiac myocytes. Electron micrographs indicated nascent intercalated
      discs were forming in foci of ES cell-derived cardiac myocytes. In addition,
      indirect immunostaining with anti-connexin 43 antibody (Ab), a monoclonal Ab to
      the gap junction component of the intercalated disc, indicated that gap junctions
      were present in contracting ES cell foci. Furthermore, microinjection of single
      cardiac myocytes with Lucifer yellow (2.5 microM) resulted in the spread of
      fluorescence to adjacent cells within a contracting focus, an indication of
      functional cell-cell coupling across these gap junctions. Together, these results
      indicate ES cell-derived cardiac myocytes exhibit cell morphology, sarcomere
      formation, and cell-cell junctions similar to those observed in cardiac myocytes
      developing in vivo.

PMID- 8986377
TI  - Pre-mitotic nuclear migration in subsidiary mother cells of Tradescantia occurs
      in G1 of the cell cycle and requires F-actin.
AB  - We have studied pre-mitotic nuclear migration in living subsidiary mother cells
      (SMCs) of Tradescantia virginiana. Divisions in the four SMCs of each stomatal
      complex are asymmetrical and are preceded by the migration of nuclei from random
      locations in the cells to positions adjacent to the central guard mother cells
      (GMCs). In newly polarised SMCs, nuclei display erratic movements which gradually
      dampen over time. In older complexes, where nuclear migration occurred earlier in
      the ontogeny of the leaf, nuclei are stably positioned and change in morphology
      from spherical to dome-shaped. Labelling with bromodeoxyuridine (BrdU) shows that
      SMCs polarised in G1 of the cell cycle and remain polarised for a minimum of 22 h
      before entering mitosis, while the inducing GMCs stay in G1. Centrifugation
      (1,320 g, 15 min) of epidermal peels displaces the majority of nuclei to the
      centrifugal end of cells, including nuclei in polarised SMCs. After
      centrifugation, most SMC nuclei return towards the GMCs within 100 min in control
      and 5 microM oryzalin treated peels. However, nuclei are unable to reposition in
      the presence of cytochalasin B (5 micrograms/ml). Thus, the signal for SMC
      polarisation is issued very early in the ontogeny of the cells (G1), is
      apparently sustained for a prolonged period, and results in the actin-dependent
      migration of nuclei towards the GMC. Cytological changes and nuclear migrations
      similar to those occurring in polarising SMCs can be induced by a local
      application of pressure to the surface of epidermal cells.

PMID- 8986378
TI  - Beat frequency difference between the two flagella of Chlamydomonas depends on
      the attachment site of outer dynein arms on the outer-doublet microtubules.
AB  - The two flagella of Chlamydomonas, although similar to each other at first
      glance, differ in functional properties. A clear difference exists in the beat
      frequency: the trans-flagellum (the one farthest from the eyespot) beats with 30
      40% higher frequency than the cis-flagellum (the one nearest to the eyespot) in
      demembranated and reactivated cell models. This difference is considered to be
      influenced by outer arm dynein, because the two flagella beat at almost the same
      frequency in cell models of oda mutants lacking the outer dynein arm. When a
      sample of outer arm dynein extracted and purified from the wild-type axoneme was
      mixed with the cell models of an oda mutant, oda1, an almost normal number of
      outer dynein arms became attached to the axonemes, and the wild-type level of
      beat frequency was recovered on reactivation with ATP addition. The frequency
      imbalance, however, was not restored. Unexpectedly, when a similar experiment was
      performed with the cell model of another oda mutant, oda6, the addition of outer
      arm dynein restored the cis-trans frequency imbalance in addition to the normal
      number of outer arms and the higher level of reactivated motility. Among other
      oda mutants, oda3 yielded results similar to those with oda1, whereas oda2, oda4,
      and oda5 yielded results similar to those with oda6. Because the only structural
      difference between the two groups of oda mutants is that the oda1 and oda3
      axonemes lack the outer arm attachment site on the outer doublet A-tubule while
      the axonemes of the other mutants retain it, these findings suggest that the
      attachment site for the outer dynein arm is important in determining the
      flagellar beat frequency. This suggests that the basal portion of the outer arm
      dynein is important in regulating the flagellar activity and therefore the
      behavior of the cell.

PMID- 8986379
TI  - Tubulin assembly in the presence of calcium ions and taxol: microtubule bundling
      and formation of macrotubule-ring complexes.
AB  - It has been confirmed that taxol is able to prevent Ca(2+)-induced inhibition of
      microtubule formation from tubulin in the presence of microtubule-associated
      proteins. However, by means of electron microscopy and scanning force microscopy
      it could be demonstrated that assembly in the presence of Ca2+ and taxol leads to
      structural aberrations. The kind of aberration depends on the order of addition
      of taxol and Ca2+ to tubulin. When taxol was added first, microtubules were
      formed preferentially. But, these microtubules typically associated with each
      other by close wall-to-wall alignments or they formed complexes with some C
      shaped protofilament ribbons, resulting in microtubule bundles or doublet- and
      triplet-like microtubule structures, respectively. When Ca2+ was added first,
      macrotubules, rings, and ring crystals were the dominant assembly products.
      Mostly, the macrotubules were also bundled or they enclosed rings in their lumen.
      The findings clearly demonstrate the potency of Ca2+ to induce different
      polymorphic assemblies with additional protofilament associations, not realized
      in microtubules.

PMID- 8986380
TI  - Nonrandom chromosome segregation in male meiosis of a sciarid fly: elimination of
      paternal chromosomes in first division is mediated by non-kinetochore
      microtubules.
AB  - The mechanism of nonrandom chromosome segregation and elimination in male first
      meiotic division of sciarid flies is one of the enigmas of classical
      cytogenetics. Interpretations of the available data regarding this unusual
      chromosome transport are contradictory [reviewed by Gerbi, 1986: "Germline-Soma
      Differentiations. Results and Problems of Cell Differentiation," Vol. 13:71-104].
      In the present study of spermatogenesis in Trichosia pubescens the process is
      reinvestigated by indirect anti-tubulin immunofluorescence labeling of spindle
      microtubules and DAPI chromosome staining, partly in combination with ultrathin
      sectioning and electron microscopy. While the maternal homologues and the sex
      limited (L) chromosomes seem to be transported very quickly toward the pole of
      the monopolar spindle, where they stay throughout first meiotic division,
      paternal homologues remain some distance from the pole, stick together, and, as
      an undifferentiated cluster of chromatin, withdraw from the pole in the course of
      division. Finally the paternal chromatin becomes eliminated in a cytoplasmic bud
      which is cast off. The different behavior of maternal homologues (and L
      chromosomes) and paternal homologues may be caused by differences in kinetochore
      structure and function. In contrast to maternal and L chromosomes, the paternal
      homologues do not display structurally defined kinetochore-like regions and seem
      to be unable to orient poleward. During the process of elimination, a prominent
      bundle of pole-oriented microtubules is associated with the paternal chromatin
      cluster. It is suggested that transport away from the pole is brought about by
      these microtubules. Thus, meiotic chromosome elimination in sciarids may be
      related to mechanisms involving "polar ejection forces" [Rieder et al., 1986: J.
      Cell Biol. 103:581-591].

PMID- 8986381
TI  - Imaging of articular pathology: MRI, CT, arthrography.
AB  - The purpose of this review article is to present the advantages and limitations
      of magnetic resonance imaging (MRI), computed tomography (CT) and arthrography
      for evaluating articular pathology. Techniques, patient selection, indications
      and contraindications for each modality are reviewed. MRI provides superior soft
      tissue contrast and image plane selection, making it the ideal technique for most
      articular abnormalities. However, obese patients and patients with certain
      electrical or metallic implants cannot be examined with MRI. CT provides superior
      detail for fine cortical bone and subtle calcifications, but lacks the soft
      tissue contrast provided by MRI. Arthrography is an invasive technique with
      minimal risk of allergy to contrast material or infection. This technique permits
      accurate measurement of capsular volume, allows for fluid aspiration for
      laboratory studies and permits injection of anesthetic and/or steroid compounds
      for purposes of treatment or confirming the site of the patient's pain. Magnetic
      resonance imaging, computed tomography and arthrography are useful techniques for
      evaluating articular pathology. Careful review of the clinical symptoms and
      patient's condition is necessary to select the most appropriate technique.

PMID- 8986382
TI  - A contribution by the ascending pharyngeal artery to the arterial supply of the
      odontoid process of the axis vertebra.
AB  - The origin of transverse arterial branches that contribute to the arterial supply
      of the odontoid process (dens axis) is not clear. Dissections were performed on
      20 injected fetal and adult human cranio-cervical junctions to demonstrate the
      origin of the arteries that contribute feeding branches to the arteries supplying
      the neck of the odontoid process. At its termination near the anterior arch of
      the atlas, the ascending pharyngeal artery gave off transverse branches that
      anastomosed with the anterior ascending arteries to the odontoid process. It also
      gave off a branch that traversed the hypoglossal canal and anastomosed with the
      posterior ascending artery. A small branch linked the posterior ascending artery
      to the first transverse branch. This investigation complements previous work on
      the arterial supply to the odontoid process.

PMID- 8986383
TI  - A study of the normal position of auricle in neonates.
AB  - The term "low-set ears" has been in common use for several decades to describe
      various malformation syndromes. But an accurate description of the normal
      position of the auricles is lacking in relevant literature. This study was
      designed to determine the normal position of auricles using bony landmarks that
      are less variable. The normal position of the auricle was determined in 1,000
      neonates without any obvious congenital anomalies. A fixed bony point (point z)
      on the upper border of the posterior part of the zygomatic process of the
      temporal bone opposite the condyle of the mandible was selected. This point lies
      in front of the auricle and is easily palpable in neonates. The distance between
      point z and the upper and lower attachments of the auricle were measured as well
      as the distance between point z and the upper and lower poles of the auricle. The
      results were compared between the two sexes and between right and left sides.
      There was a wide variation in the distances measured in normal neonates. This
      highlights the importance of redefining the term "low-set ears."

PMID- 8986384
TI  - Morphology of the corpus callosum in human fetuses.
AB  - Shape and size of the human fetal corpus callosum of a relatively racially
      homogeneous southern Indian sample population were studied in midsagittal
      sections of formalin fixed brains. Length of corpus callosum and width of its
      genu, body, and splenium were measured and the data statistically analyzed.
      Presence of an isthmus between the body and splenium did not correlate with the
      measured variables. There was no significant gender difference. The variables
      correlated significantly among each other but only callosal length and genu width
      correlated with gestation age. Significant absolute increase occurred in callosal
      length and genu width, whereas body and splenium widths remained the same. Simple
      regression equations to estimate the callosal length and genu width for a given
      age are derived.

PMID- 8986385
TI  - The calcar femorale: a tale of historical neglect.
AB  - The term calcar femorale (originally referring to a bony spur projecting into the
      cancellous tissue of the base of the femoral neck) differs from most anatomical
      terms in that it has developed separate meanings in different areas of use. In
      particular, its present meaning for most orthopedic surgeons differs from its
      classical anatomical significance. This work shows that the classical, "textbook"
      anatomical interpretation-usually attributed to Merkel (1874, cited by Harty,
      1957, J. Bone Joint Surg. [Am.] 39:625-630)-is not entirely correct, being based
      on an incomplete appreciation of the true nature of the three-dimensional
      structure of the upper end of the femur. Though Humphry (1858, A Treatise on the
      Human Skeleton, Cambridge, England: Macmillan) was aware of the importance of the
      third dimension, it was the largely neglected work of Dixon (1910, J. Anat.
      Physiol., 44:223-230), itself published to draw attention to the ideas of Krause
      (1909, in Bardeleben's Handbuch der Anatomie des Menschen, Jena: Gustav Fischer),
      which indicated the true nature of the calcar femorale and the limitations of
      Merkel's view. Dixon's work has been developed and consolidated by others such as
      Garden (1961, J. Bone Joint Surg. [Br.] 43:576-589), who was apparently unaware
      of Dixon, just as Dixon himself appears to have been unaware of the work of
      Bigelow (1875, published in Bigelow, 1900, The Mechanisms of Dislocations and
      Fracture of the Hip, Boston: Little, Brown), which pre-empted one of his major
      concepts. Even earlier work by Bigelow (1869, published in Bigelow; 1900, The
      Mechanisms of Dislocations and Fracture of the Hip, Boston: Little, Brown)
      appears to have pre-empted that of Merkel. The adoption of the three-dimensional,
      "Dixon concept" of the bony anatomy of the upper end of the femur leads to an
      entirely different set of structural engineering analogies from those two
      dimensional ones which have become commonplace since the work of Ward (1838,
      cited by Garden, 1961, J. Bone Joint Surg. [Br.] 43:576-589) and Wolff (1870,
      cited by Keith, 1919, Menders of the Maimed, London: Frowde and Hodder &
      Stoughton).

PMID- 8986386
TI  - Anatomy departments and anatomy education: reflections and myths.
AB  - This report is based on the basic postulate that if the overall goal of anatomy
      departments is to function as vigorous academic and scholastic communities
      welcoming research and innovative thinking, there will be implications for the
      nature of anatomy teaching. In developing this theme, perceptions about the
      meaning of the term "anatomy" are explored, as are the repercussions of teaching
      anatomy entirely within the context of a medical curriculum. There have been a
      variety of responses to the perceived demise of anatomy, resulting in a
      discipline that is heterogeneous, both in terms of teaching and research
      emphases. The options open to university departments are assessed by way of the
      model of third-wave departments, with their characteristics of excellence,
      flexibility, planning, networking, and risk-taking. The consequences of this
      model for anatomy departments include the importance of a research emphasis, a
      close conceptual link between teaching and research, and a structural base for
      the research. In view of these consequences, three distinct forms of teaching are
      recognized: undergraduate teaching to medical and other health science students,
      undergraduate teaching to science students, and postgraduate teaching. Some of
      the distinctive features of the two forms of undergraduate teaching are explored.
      Various central contentions (myths) regarding anatomy departments and anatomy
      education are rejected.

PMID- 8986387
TI  - Anatomy into the next millennium: quo vadis, or simply where to?
AB  - Concerns are raised regarding the status of anatomy as an academic discipline and
      its future. The traditional place of anatomy in the medical and other curricula
      is under serious threat. There is a decline in the number of clinically qualified
      academic staff members in anatomy departments. Options for change if anatomy is
      to remain among viable academic disciplines are explored.

PMID- 8986389
TI  - Is inguinal hernia a defect in human evolution and would this insight improve
      concepts for methods of surgical repair?
AB  - In Homo sapiens sapiens and many mammalian quadrupeds, there is an absence of the
      posterior rectus sheath below the arcuate line (of Douglas) and an insubstantial
      transversalis fascia in the groin. This anatomical arrangement presents no
      particular functional anatomic difficulty for quadrupeds as their inguinal canal
      is directed "uphill" during ambulation and therefore is not subjected to
      significant gravitational stress. In humans, however, gravitational stress
      necessitated by erect posture, including bearing the weight of the intra
      abdominal organs directed toward the lower abdomen, considerably amplifies this
      intrinsic anatomic weakness. It allows a significant number of pathologic
      inguinal hernias, both direct and indirect, to become clinically manifest and
      associated with a coincident increase in morbidity and mortality, especially in
      patients with strangulated hernias and/or delayed treatment. The morbidity is
      associated with a significant national economic loss secondary to work hour loss
      from pain, discomfort, surgical treatment, and rehabilitation following therapy.
      The mortality is usually associated with strangulation, especially in those in
      patients with delayed treatment. The lack of the evolutionary development of a
      strong posterior rectus sheath and transversalis fascia in the lower abdomen is
      thought to represent a significant specific anatomic defect in the evolution of
      humankind. If so, then perhaps methods for surgical repair will be directed
      toward correction of this defect and avoid, not encourage, such methods as the
      utilization of the weak or absent transversalis "fascia," which are doomed to a
      high recurrence rate, or other methods that are unnecessarily complicated, such
      as certain laparoscopic repairs of inguinal hernia.

PMID- 8986390
TI  - Anomalous first septal perforator artery.

PMID- 8986391
TI  - A clinical anatomy curriculum for the medical student of the 21st century: gross
      anatomy.

PMID- 8986392
TI  - Anatomy departments and anatomy education: reflections and myths.

PMID- 8986393
TI  - Keratinocytes and cytokine/growth factors.
AB  - Cytokines are polypeptide growth factors produced by most nucleated cells in the
      body, including epithelial cells, keratinocytes, and Langerhans cells in the
      skin. Cytokines can be classified into interleukins, tumor necrosis factors,
      chemokines, colony-stimulating factor, interferons, and growth factors. Like
      classic hormones, cytokines bind to specific receptors to transmit their messages
      to target cells. Cytokine receptors can be divided into three cytokine receptor
      superfamilies: the immunoglobulin superfamily, the hematopoietin family, and the
      tumor necrosis factor family. Following cytokine/cytokine-receptor binding (first
      messenger), a signal transduction pathway is initiated. Factors affecting
      homeostasis in the skin and oral mucosa include a delicate balance between
      cytokines/cytokine-receptors and their antagonists. An imbalance in these
      variables can influence the development of cutaneous and oral diseases-such as
      lichen planus, autoimmune disorders, and some neoplastic processes- and can
      affect wound healing. Potential uses of cytokines include cancer and antiviral
      therapy.

PMID- 8986394
TI  - Molecular biology of human oral cancer.
AB  - The application of molecular biological tools to the study of cancer has
      significantly advanced the field of human cancer research. Such study has
      demonstrated the involvement of two classes of highly conserved cellular genes in
      the malignant transformation process: oncogenes and tumor suppressor genes.
      Despite these advances in the molecular biology of human cancers, our
      understanding of human oral cancer lags behind that of cancer of other body
      sites. This review attempts to assess the current status of the molecular biology
      of human oral cancer.

PMID- 8986395
TI  - The role of implant surface characteristics in the healing of bone.
AB  - The surface of an implant determines its ultimate ability to integrate into the
      surrounding tissue. The composite effect of surface energy, composition,
      roughness, and topography plays a major role during the initial phases of the
      biological response to the implant, such as protein adsorption and cellular
      adherence, as well as during the later and more chronic phases of the response.
      For bone, the successful incorporation (and hence rigid fixation) of an
      alloplastic material within the surrounding bony bed is called osteointegration.
      The exact surface characteristics necessary for optimal osteointegration,
      however, remain to be elucidated. This review will focus on how surface
      characteristics, such as composition and roughness, affect cellular response to
      an implant material. Data from two different culture systems suggest that these
      characteristics play a significant role in the recruitment and maturation of
      cells along relevant differentiation pathways. In the case of osteointegration,
      if the implant surface is inappropriate or less than optimal, cells will be
      unable to produce the appropriate complement of autocrine and paracrine factors
      required for adequate stimulation of osteogenesis at the implant site. In
      contrast, if the surface is appropriate, cells at the implant surface will
      stimulate interactions between cells at the surface and those in distal tissues.
      This, in turn, will initiate a timely sequence of events which include cell
      proliferation, differentiation, matrix synthesis, and local factor production,
      thereby resulting in the successful incorporation of the implant into the
      surrounding bony tissue.

PMID- 8986396
TI  - Advanced imaging methods.
AB  - Recent developments in imaging sciences have enabled dental researchers to
      visualize structural and biophysical changes effectively. New approaches for
      intra-oral radiography allow investigators to conduct densitometric assessments
      of dento-alveolar structures. Longitudinal changes in alveolar bone can be
      studied by computer-assisted image analysis programs. These techniques have been
      applied to dimensional analysis of the alveolar crest, detection of gain or loss
      of alveolar bone density, peri-implant bone healing, and caries detection. Dental
      applications of computed tomography (CT) include the detailed radiologic anatomy
      of alveolar processes, orofacial soft tissues and air spaces, and developmental
      defects. Image analysis software permits bone mass mineralization to be
      quantified by means of CT data. CT has also been used to study salivary gland
      disease, injuries of the facial skeleton, and dental implant treatment planning.
      Magnetic resonance imaging (MRI) has been used extensively in retrospective and
      prospective studies of internal derangements of the temporomandibular joint.
      Assessments based on MRI imaging of the salivary glands, paranasal sinuses, and
      cerebrovascular disease have also been reported. Magnetic resonance spectroscopy
      (MRS) has been applied to the study of skeletal muscle, tumors, and to monitor
      the healing of grafts. Nuclear imaging provides a sensitive technique for early
      detection of physiological changes in soft tissue and bone. It has been used in
      studies of periodontitis, osteomyelitis, oral and maxillofacial tumors, stress
      fractures, bone healing, temporomandibular joint, and blood flow. This article
      includes brief descriptions of the technical principles of each imaging modality,
      reviews their previous uses in oral biology research, and discusses potential
      future applications in research protocols.

PMID- 8986397
TI  - Scientific creativity in biomedical research: some case histories.
AB  - It is for me a pleasure, and a great honor, to be able to present the official
      lecture honoring the retirement of Professor Johannes Buttner. I first came to
      know Professor Buttner more than fifteen years ago, when he came to Yale
      University to give a lecture in 1980. I value highly his many stimulating works
      in the field of the history of clinical chemistry. I would draw attention
      particularly to his elegant studies of the origin of clinical chemistry as a
      discipline, and of the first chemical laboratories established in clinics (1, 2).
      I hope very much that, after his retirement, he will have many years to pursue
      these important themes further.

PMID- 8986398
TI  - Clinical expression of a rare beta-globin gene mutation co-inherited with
      haemoglobin E-disease.
AB  - A single nucleotide substitution and the effect on the phenotype in an Indonesian
      family with beta-thalassaemia, HbE-trait and HbE-beta-thalassaemia is described.
      In the proposita (female, age 20 (Hb 7.4 mmol/l; MCV 72 fl; MCH 1.45 fmol; HbA2
      3.5%; HbF 2.4%)). An A/G mutation in the RNA cleavage and polyadenylation
      sequence was detected (AATAAA/AATAGA). Her sister (Hb 8.2 mmol/l; MCV 77 fl; MCH
      1.60 fmol; HbA2/HbE 32.4%), carried a different mutation in the beta-globin gene
      (codon 25; G129/A), and consequently had HbE-trait. Their mother had a
      haemoglobin concentration of 6.4 mmol/l (MCV 56 fl; MCH 1.20 fmol; HbA2/HbE
      55.8%). She was compound heterozygous for the mutation in the poly A-signal and
      HbE-trait. Using restriction enzyme analysis and linkage studies, we subsequently
      identified six family members with HbE-beta-thalassaemia, five with beta
      thalassaemia and six with HbE-trait. Two individuals were unaffected. The
      mutation in the polyadenylation sequence causes a mild form of beta (+)
      thalassaemia. The MCV and MCH in individuals with both beta-thalassaemia and HbE
      trait were significantly lower, yet on average they were only slightly more
      anaemic than those carrying only the thalassaemic gene.

PMID- 8986399
TI  - Fast amplification of the low density lipoprotein receptor gene and detection of
      a large deletion by means of long polymerase chain reaction.
AB  - To demonstrate the usefulness of Long PCR in analyzing gene structures and large
      deletions we have developed a method to amplify the entire LDL receptor gene,
      including the promoter region and intron 1. This opens new ways for studies of
      the gene and allows the detection of certain LDL receptor-specific deletions. For
      the amplification of the LDL receptor gene, spanning approximately 45.5 x 10(3)
      bases and divided into 18 exons and 17 introns, we have designed overlapping PCR
      products (ranging from 4 to 16 x 10(3) bases in length), which can be amplified
      simultaneously overnight for fast results. It was possible to positively identify
      two samples from heterozygote carriers of the "5 kB French-Canadian" deletion
      using this method. As a side result the length of intron 1 of the LDL receptor
      gene could be established to be approximately 9.5 x 10(3) bases. The method is
      sensitive enough to detect deletions in 1:10 mixes of positive control with
      wildtype DNA.

PMID- 8986400
TI  - Age-dependent variations of lactate dehydrogenase and creatine kinase activities
      in water buffalo calf serum.
AB  - The electrophoretic patterns of the serum enzymes lactate dehydrogenase and
      creatine kinase from water buffalo calves are described. Differences in total
      activities as well as their relative distribution were seen at ages ranging from
      1 to 10 weeks. While total lactate dehydrogenase activity increased by over 100%,
      total creatine kinase increased by almost 400%. The relative activities of
      lactate dehydrogenase 1 and 5 decreased with age. Lactate dehydrogenase 2 and 3
      increased and lactate dehydrogenase 4 did not change. In relation to creatine
      kinase, the prevalent isoenzyme was creatine kinase-MM, but it's relative
      activity gradually decreased in comparison to the other two isoenzymes (creatine
      kinase-MB and creatine kinase-BB). Creatine kinase-BB was completely absent until
      the 3rd week of age. The percentage modifications of creatine kinase isoenzymes
      were correlated to age. The results suggest that isoenzymatic separation and
      characterization of lactate dehydrogenase and creatine kinase in relation to the
      various tissues can significantly contribute to the diagnosis of diseases which
      are linked to tissue damage.

PMID- 8986401
TI  - gamma-Glutamyltransferase and serum proteins in buffalo calves following
      colostral ingestion.
AB  - Catalytic activity concentrations of gamma-glutamyltransferase in blood were
      determined for the evaluation of colostral ingestion. gamma-Glutamyltransferase
      levels were compared with those of total proteins, albumins and total globulins
      in the serum, showing good correlation at 2-3 days after birth. gamma
      Glutamyltransferase was determined using the Boehringer Mannheim "Reflotron" dry
      chemistry enzyme strips. After colostral ingestion, blood gamma
      glutamyltransferase increased from 35 +/- 19 U/l at birth to 1563 +/- 1283 U/l.
      Electrophoretic separation of total proteins showed an increase of serum gamma
      globulins from 4.2 g/l before ingestion to 32.9 g/l after ingestion. The same
      analytes were determined in colostrum showing the major protein fraction to be
      gamma-globulins. gamma-Globulins and gamma-glutamyltransferase permeate to the
      blood stream, and there is a good correlation between them. The enzyme gamma
      glutamyltransferase can be used as an equivalent for the determination of gamma
      globulins in the calf serum and the degree of colostral ingestion.

PMID- 8986402
TI  - Determination of adenosine phosphates in whole blood by capillary zone
      electrophoresis.
AB  - The pool of chemical energy in an organism represented by high-energy compounds
      can be assessed by means of adenosine triphosphate (ATP) determination in whole
      blood and tissues. The elegant manner for the determination of adenosine
      phosphates (ATP, ADP, AMP) in a single assay is offered by the technique of
      capillary zone electrophoresis. For this purpose, the BioFocus 3000 Capillary
      Electrophoresis System (BIO-RAD Laboratories, Inc., Hercules, CA, USA) was used.
      For the construction of calibration curves, pure preparations of ATP, ADP and AMP
      were analyzed. The method was used for adenosine phosphates determination in the
      umbilical blood samples from physiological and immature newborns. Capillary zone
      electrophoresis enables a specific and simultaneous determination of adenosine
      phosphates and, thus, monitoring of unusual metabolic situations.

PMID- 8986403
TI  - Bilirubin and metamizol do not interfere with the randox enzymatic creatinine
      test. An evaluation of a new enzymatic creatinine determination method.
AB  - We evaluated the new commercially available enzymatic test kit for creatinine
      (Randox Laboratories Ltd. Ardmore, Crumlin, UK). The test correlated well with
      the reference HPLC method (yenz = 0.98x + 1.4; r = 1.00; n = 72). The
      correlations with the Jaffe method (yenz = 1.00x + 14.1; r = 0.99; n = 72) and
      the dry slide technique (yenz = 1.07x + 4.1; r = 1.00; n = 72) were also good,
      but these techniques gave slightly higher creatinine results than the HPLC or the
      Randox enzymatic method. This new test is insensitive to bilirubin interference.
      It has been reported that patients receiving metamizol showed unusually low
      values of creatinine, when determined enzymatically, but this drug does not
      interfere with the Randox method. The test evaluated is more specific than
      enzymatic methods published earlier and it provides an attractive alternative to
      the traditional picrate test.

PMID- 8986404
TI  - Improvement of the systematic predilution error of the Boehringer Mannheim
      Hitachi 911 analyzer.

PMID- 8986405
TI  - Daily intra-individual variability of lipoprotein(a) in serum.

PMID- 8986406
TI  - Influence of the presence or absence of pyridoxal-5'-phosphate in control sera on
      the interlaboratory comparability in measuring aspartate aminotransferase
      catalytic concentration.

PMID- 8986407
TI  - Proposed guidelines for the internal quality control of analytical results in the
      medical laboratory.
AB  - The factors involved in analytical quality relate to definition of quality,
      creation of quality, and control of quality, and errors arise from external and
      internal sources as well as from permanent and variable factors. Further, the two
      main types of error are classified as systematic and random errors. Internal
      quality control (IQC) systems can only operate on the variable factors which are
      related to batch-to-batch variations (external factors) and to the performance in
      the laboratory (internal factors). In creating an adequate internal control
      system, several problems are faced: (i) quality of control materials, (ii) types
      and frequency of possible errors, (iii) number and types of control materials,
      (iv) number of replicates of the control, (v) probability of error detection,
      (vi) probability of false rejection, (vii) consequences of reject signals, (viii)
      trouble-shooting systems, and (ix) prevention of errors among many other
      conditions. Gaussian distributions of control results are assumed and the
      statistical control rules are evaluated in relation to probability of false
      rejections, Pfr, and probability of error detection, Ped, for the different
      rules. Combinations of low Pfr and high Ped are obtained by combining results
      from e.g. four measurements of the same control sample by use of mean and range
      rules. Further, it is not possible to establish a common control system which can
      be used for all quantities and analytical procedures; on the contrary, each
      procedure should have its particular efficient IQC system. These aspects are
      discussed and a number of guidelines for statistical control rules and problem
      related internal quality control are presented.

PMID- 8986408
TI  - The role of the target organ in the development of autoimmune diseases
      exemplified in the obese strain (OS) chicken model for human Hashimoto disease.

PMID- 8986409
TI  - The obese strain chicken as a model for human Hashimoto's thyroiditis.
AB  - The OS and the related Cornell C strain are interesting animal models for the
      study of the etiology of autoimmune thyroiditis. They are especially valuable for
      studying the etiologic role of thyroid abnormalities and abnormalities in the
      processing of iodine. Limitations of the model are the scarcity of immunological
      reagents for chickens, the absence of avian cloned thyroid-specific genes,
      minimal amounts of microsomal antibody and some differences between OS chickens
      and Hashimoto's patients in the types of thyroid abnormalities observed.

PMID- 8986410
TI  - The biobreeding Worcester rat--a model of organ-specific autoimmunity.

PMID- 8986411
TI  - The BB rat as a model for autoimmune thyroiditis: relevance for the pathogenesis
      of human disease.

PMID- 8986412
TI  - Autoimmune thyroiditis--spontaneous disease models--cat.

PMID- 8986414
TI  - Iodine-induced thyroiditis in the non-obese diabetic (NOD) mouse--more questions
      than answers.

PMID- 8986413
TI  - The non-obese diabetic (NOD) mouse: an animal model for autoimmune thyroiditis.
AB  - The NOD mouse, an ideal model for insulin-dependent diabetes mellitus, is also
      useful to study the pathogenesis of autoimmune thyroiditis. Spontaneous
      thyroiditis greatly varies in frequency among NOD colonies, but Hashimoto-like
      thyroiditis can be induced in two experimental models: goiter involution after
      iodide administration and immunization by TSH receptor, described hereunder.

PMID- 8986416
TI  - Induction models of autoimmune thyroid disease--critical comments.

PMID- 8986415
TI  - Induction of experimental autoimmune thyroiditis (EAT) by heat-denaturated
      thyroglobulin (Tg).
AB  - Experimental Autoimmune Thyroiditis (EAT) is characterized by autoreactive T and
      B cell responses, assessed by a marked lymphocytic infiltration of the thyroid
      gland by T cells and the occurrence of circulating autoantibodies (AAb) to
      thyroglobulin (Tg). It was recently reported that administration of denaturated
      exogenous antigens primes class I-restricted cytotoxic T cells in vivo. Since
      cytotoxic T cells are involved in EAT development, porcine Tg (pTg) was heat
      denaturated, i.v. injected into CBA/J mice and features of EAT evaluated.
      Simultaneously, mice were immunized with pTg and adjuvants and evaluation of EAT
      performed. We found that heat-denaturated pTg (hdpTg) induced EAT in recipient
      mice similar to native pTg/adjuvants. Surprisingly, whereas Tg-specific cytotoxic
      T cells were regularly found in lymph node cells from hdpTg or native pTg
      immunized mice, proliferative responses were only detected using T cells from
      native pTg immunized mice. Autoantibodies to pTg were decreased by a factor 30 in
      sera from mice immunized with hdpTg. These data further emphasized the role of Tg
      specific cytotoxic T cells in EAT.

PMID- 8986417
TI  - Experimental autoimmunity to thyrotropin receptor.
AB  - Since the cloning of a full length cDNA encoding the thyrotropin receptor (TSHr),
      several laboratories have been actively trying to develop an optimal animal model
      to understand the pathogenesis of TSHr mediated autoimmune diseases and have made
      considerable progress. To date, results from our laboratory have indicated that
      the nature of the antigen, and the adjuvant used for immunization, immunogenetic
      background of the animal and fine specificities of antibodies elicited might play
      an important role in determining the qualitative nature of the antibody response.
      Although an ideal animal model for either Graves' disease or primary myxedema is
      not yet available, ongoing studies in our laboratory and elsewhere hold promise
      for establishing animal models for various TSHr mediated autoimmune diseases in
      the near future.

PMID- 8986418
TI  - Immunopathogenicity of thyrotropin receptor--ability to induce autoimmune thyroid
      disease in an experimental animal model.

PMID- 8986419
TI  - Graves' disease: xenotransplantation model (athymic nude mice).

PMID- 8986420
TI  - Graves' disease/model of SCID mouse.
AB  - The severe combined immunodeficient (SCID) mouse constitutes an interesting but
      not ideal model for the study of human Graves' disease (GD) thyroid tissue. While
      certainly thyroid tissue survives in the SCID mouse, the lymphocytes do not seem
      to be able to exert their effects in a long term manner as they do in the human
      host. Primary thyroid xenografts of GD will not remain hyperfunctional, and
      antibodies seem to subside after several weeks. GD thyroid tissue which has been
      removed from its immune environment by passing it through the nude mouse for
      eight weeks, and then re-xenografted in the SCID mouse, will again manifest
      lymphocytic infiltration only upon injection of autologous human peripheral blood
      mononuclear cells which thus reconstitute the lesion to some degree. However, we
      have not been able to reproduce GD by this procedure. We have been able to show
      organ-specific homing of the autologous peripheral blood lymphocytes to the GD
      thyroid tissue and a reappearance of histological lymphocytic infiltration,
      thyrocyte HLA-DR and ICAM-1 expression, and the reappearance of circulating
      thyroid autoantibodies after injection of autologous peripheral blood mononuclear
      cells (PBMC). (No such changes occur when normal thyroid tissue is similarly
      studied). This can be greatly magnified by deleting the CD8 cells prior to (PBMC)
      injection and can be prevented by adding a surfeit of CD8 cells instead,
      signifying that this subpopulation of lymphocytes contains suppressor T
      lymphocytes. The model affords means of studying various immunomodulators in an
      in vivo situation. Attempts are being made in various centres to more closely
      simulate GD but it may be necessary to have other mouse models with fewer natural
      killer (NK) cells to be able to successfully maintain the lymphocytes and tissue
      in its original state.

PMID- 8986421
TI  - The SCID mouse model: a discussion.

PMID- 8986423
TI  - Transgenic mice models in autoimmunity--discussion.
AB  - Transgenic mice are an important in vivo model for studying the function of
      single genes. Specific induction and tissue specific expression of the inserted
      genes are the great advantages of this system. However, there a risks in
      constructing transgenic mice and the interpretation of the experimental data. To
      prevent artefacts and to optimize the transgenic model, the experimental systems
      have to fulfill the following presets: 1. Experiments has to be done with a
      stable transgenic line and not with the first heterogeneous transgeniced
      generation, because they differ in their site of gene insertion and in the
      cellular response. 2. The number of experiments have to be statistically
      sufficient. Often only a few number of experiments are done, due to the bad
      reproduction of transgenic mice. 3. Health of transgenic mice has to be proven,
      since the transgenic animals are under laboratory conditions and not under
      professional breeding conditions. 4. As a control there should be a transgenic
      mouse with a comparable pseudogene insertion beside the normal littermate
      control, to exclude artefacts by the simple gene insertion. If all of these
      presets are fulfilled, a transgenic mice model will be one of the best
      experimental systems.

PMID- 8986422
TI  - Transgenic models for proliferative and hyperfunctional thyroid diseases.
AB  - Mouse transgenic models that develop thyroid diseases were generated. All
      transgenes were driven by the thyroid specific promoter of the thyroglobulin
      gene. The tissue specificity of the promoter was investigated by using the
      bacterial chloramphenicol acetyl transferase gene as reporter. The expression of
      an adenosine A2a receptor resulted in the permanent activation of the cAMP
      cascade. As a consequence, the transgenic mice developed severe hyperthyroidism
      and a large goiter, demonstrating in vivo the role of the cAMP cascade in the
      promotion of both function and proliferation of the thyroid cell. These mice
      constitute a model for autonomous hyperfunctional adenoma and non-autoimmune
      familial hyperthyroidism, where mutant thyrotropin receptors stimulate the cAMP
      cascade constitutively. In another transgenic model, the function of the
      retinoblastoma susceptibility gene product RB1 (and of related proteins) was
      inhibited by expression of the E7 oncoprotein of human papillomavirus type 16.
      The result was the development of a differentiated and normofunctional colloid
      goiter, with the progressive development of differentiated malignant lesions.
      This model suggests the essential role of RB1 and related proteins in the
      negative control of proliferation that characterizes thyroid cells in the adult.
      Other transgenic models of thyroid diseases are discussed.

PMID- 8986424
TI  - What could mice tell us about goiter or other benign thyroid diseases?
AB  - Several lines of research have been developed by using mice as animal models,
      including goiter development and involution, nodules formation and congenital
      hypothyroidism. They are reviewed and discussed as potential tools to better
      understand the thyroid pathophysiology.

PMID- 8986425
TI  - Continuous vs. pulsatile administration of thyrotropin-releasing hormone (TRH) in
      the model of the chronically cannulated rat: long-term effects on thyroid
      function.
AB  - Thyroid-stimulating hormone (TSH) belongs to a family of glycoprotein hormones
      secreted by the anterior lobe of the pituitary gland in a pulsatile fashion.
      Although this pulsatile pattern of release has been characterized by several
      groups, its exact physiological relevance remains to be elucidated. We
      established a model of a chronically cannulated rat allowing us to apply
      quantified pulses of thyrotropin-releasing hormone intravenously and to monitor
      the biological response on the anterior pituitary as well as on the thyroid
      level. Serum rTSH, T3 and T4 levels were measured as functional parameters.
      During the five day infusion period, TSH increased under both continuous and
      pulsatile TRH stimulation, but this increase was only maintained following
      pulsatile TRH but not after continuous application. No differences between the
      continuous and the pulsatile infusion regimen could be observed in terms of TT3
      release, whereas TT4 decreased following an initial stimulation under continuous
      application, but remained stimulated during pulsatile application. Our data
      indicate that the model of the chronically cannulated rat appears to be a
      valuable tool to study the impact of the temporal pattern of TRH/TSH on thyroid
      physiology.

PMID- 8986426
TI  - Comment on: goiter benign disease.

PMID- 8986427
TI  - Model of the athymic nude mouse for the study of benign goiter disease.
AB  - Since Shimosato et al., in the mid 70s transplanted for the first time thyroid
      carcinoma tissue onto nude mice, other research groups have made use of the nude
      mouse model for the investigation of xenotransplanted thyroid tissue. The use of
      this model for the investigation of benign goiters is briefly discussed in this
      article. Normal human thyroid tissue has been transplanted either as a control in
      experiments with benign and malignant goiter tissue, or for the study of thyroid
      tissue response to stimulators such as TSH or thyroid stimulating antibodies
      (TSAb). Thyroid glands from 8- to 10-week old human fetuses obtained at the time
      of legal abortion were cryopreserved in liquid nitrogen and successfully
      transplanted into nude mice. Moreover, all the variants of human benign goiter
      tissue have been xenotransplanted: tissue from nodular and diffuse goiters, hot
      and cold nodules or goiter areas, rapidly growing nodules, etc. Two examples of
      animal thyroid tissue xenotransplantation onto nude mice are briefly discussed:
      Nude mice bearing normal thyroid tissue transplants from 4 different species
      (man, rat, pig, guinea-pig) have been used for the study of the species specific
      effect of bovine TSH and TSAb. In studies aiming at elucidating the pathogenesis
      of hyperthyroidism, toxic goiter tissue from hyperthyroid cats has been
      transplanted. In methodological terms, these experiments have shown that
      surgically removed goiter tissue can be shipped by air in cell culture medium at
      4 degrees C over long distances and then successfully transplanted.-Finally, cell
      lines such as the rat cell line FRTL-5 can be transplanted onto nude mice either
      as cell suspension or embedded in collagen, for example for the study of
      proliferation and folliculogenesis. Using the xenotransplantation model, function
      and proliferation, morphogenesis and differentiation, as well as thyroid autonomy
      and response to stimulators have all been studied in xenotransplanted human and
      animal thyroid thyroid tissue and cell lines under various experimental
      conditions. Although new research tools, for example transgenic animals, are now
      increasingly and successfully used, xenotransplantation still offers the
      possibility of addressing some specific questions which cannot be answered so
      easily with other experimental models. For example, studies with human tissue,
      involving drugs or radioactive tracers which cannot be applied to the intact
      human being, can relatively easily be performed with xenotransplanted human
      tissue and application of the drug or tracer to the host mouse. Or embryological
      development can be followed and studied using fetal thyroid (and other) tissue
      transplanted onto nude mice; here, of course, difficult ethical issues have to be
      considered. Finally, it should be mentioned that, although many scientific
      questions can be studied nowadays by cell culture or other in vitro systems,
      animal models are still needed. Extrapolation to the human being, however, should
      always be done with caution and we should always keep in mind that for the
      understanding of a human disease indeed human experimental models remain the
      goldstandard.

PMID- 8986428
TI  - In vivo models in thyroid research. The limitations of the athymic nude mice
      model for studies on goiter benign disease.

PMID- 8986430
TI  - Particularities of lysosomal storage diseases gene therapy.

PMID- 8986429
TI  - Xenotransplantation of human thyroid carcinomas in athymic nude mice.
AB  - A nude mouse xenotransplantation model was established for human thyroid
      carcinomas of different histological types. Best results of serial passages were
      obtained in anaplastic cancers. The models allowed investigations under in vivo
      conditions. Hormonal influences were tested, and imaging procedures were
      possible. In most aggressive anaplastic carcinoma cell lines, growth inhibition
      of cytostatic drugs, cytokines and nutritional effects were investigated.

PMID- 8986431
TI  - Approaches to enhance cancer radiotherapy employing gene transfer methods.
AB  - This review presents an overview and discussion of the potential synergistic
      strategies of radiation therapy and gene transfer for treating neoplastic
      disease. Topics discussed include radiation-inducible promoters coupled to genes
      which produce proteins that are cytotoxic or enhance radiosensitivity, employment
      of molecular chemotherapy approaches in conjunction with radiation therapy, and
      genetic induction of radiosensitization through modification of DNA repair,
      signal transduction, and cell cycle control genes. Additional topics discussed
      relate to gene transfer augmentation of radioimmunotherapy of cancer.
      Specifically, gene transfer methods to genetically induce tumor cells to express
      enhanced levels of cell surface antigens and receptors to increase radiolabeled
      antibody and peptide targeting and thus increase their therapeutic effect,
      selection of radionuclides for therapeutic ligand labeling, and computer
      simulation of genetic tumor-specific delivery of radiolabeled ligands are
      proposed.

PMID- 8986432
TI  - Retroviral targeted delivery.
AB  - The systemic delivery of genes will open new applications for gene therapy. The
      deployment of retroviral vectors for this purpose is being considered and
      requires the development of retroviral vectors with a defined target cell
      specificity of infection. Several reports have recently described attempts to
      engineer the envelope protein of murine retroviruses in order to expand the host
      range and enable them to infect specific human cells. The strategies are based on
      the introduction of binding sites specific for receptors on the surface of target
      cells. Although the attempts to manipulate the specificity of viral target cell
      recognition are ambitious and promising, they are not without pitfalls. We
      summarize the results obtained and the difficulties encountered.

PMID- 8986433
TI  - Optimized galenics improve in vitro gene transfer with cationic molecules up to
      1000-fold.
AB  - Reproducible and optimized complex formation between polyanionic DNA and a
      polycationic vector is a key aspect of nonviral gene transfer systems. To this
      end, several factors relevant to in vivo delivery have been tested repeatedly on
      several cell types. Gene transfer with a lipopolyamine (transfectam) in the
      presence of serum was increased over 10-fold by sequential addition of the lipid
      to DNA. Paradoxically, high complex concentrations (> 200 micrograms DNA/ml) led
      to large enhancements too, which points to the fact that formation of productive
      complexes is a slow process. Each parameter, more than compensates for the
      decreased efficiency generally observed with nonviral vectors in serum.
      Transfectam and PEI (polyethylenimine)-mediated transfection also improved after
      mild centrifugation of the complexes on to the cells. These individual factors
      were shown to be essentially multiplicative, leading altogether to approximately
      a 1000-fold transfection increase with a luciferase reporter gene. Finally, 25
      cell lines and primary cells (including fibroblasts, hepatocytes and endothelial
      cells) were successfully transfected over a five orders-of-magnitude efficiency
      range, From this large set of data, a general relation between the overall
      transfection level (as measured by luciferase reporter gene expression) and the
      fraction of transfected cells (histochemically stained for beta-galactosidase)
      could be inferred. Finally, transfectam and PEI displayed similar trends over
      this large range of efficiencies, which reinforces the hypothesis of a common
      transfection mechanism where the key endosome-releasing stop occurs through a
      "proton sponge' effect.

PMID- 8986434
TI  - Engineering a mini-herpesvirus as a general strategy to transduce up to 180 kb of
      functional self-replicating human mini-chromosomes.
AB  - The engineering of therapeutic human artificial episomal chromosomes, HAECs,
      requires the development of strategies to deliver large functional self
      replicating extrachromosomal DNA in target cells. Members of the herpesviral
      family are among the largest episomal double-stranded DNA viruses. As model
      systems of this family of endemic infectious agents, vectors derived from the
      human herpes 4 Epstein-Barr virus (EBV) were constructed which transferred up to
      180 kb of DNA packaged as infectious virions. Such a transduction strategy was
      based on a non-oncogenic helper-dependent mini-EBV carrying minimal cis elements
      for latent replication and virus production. After exposure of human B lymphoma
      and lymphoblastoid cells to mini-EBVs transducing lacZ and human HPRT minigenes,
      stable cell transformants were selected which carried the delivered multimeric
      linear DNAs as circular episomes up to 160-180 kb in size. Following transduction
      of Lesch-Nyhan disease cells with a mini-EBV/HPRT, normal human HPRT function was
      restored in cells carrying large episomal HPRT minigenes. Direct visualization of
      the therapeutic mini-EBV by fluorescent in situ hybridization (FISH) on metaphase
      and interphase nuclei indicated that 99% (556/563) of the transduced mini-EBV DNA
      was episomal with an average copy number of one to two per nucleus. This system
      should allow the delivery of large genes in common diseases such as hemophilia A
      and codelivery of multiple genes in cells from polygenic diseases such as cancer.
      The extrachromosomal mini-EBV-based strategy offers an alternative to integrative
      or non-replicating gene therapy infectious vectors, which may be generally
      applicable to other herpesviruses characterized by different tropisms.

PMID- 8986435
TI  - Gene transfer to the rabbit patellar tendon: potential for genetic enhancement of
      tendon and ligament healing.
AB  - Injuries to ligaments and tendons occur very commonly, but often heal very
      poorly. A number of growth factors show promise as biological agents with which
      to augment the reparative responses of these tissues, but they are extremely
      difficult to deliver clinically. We have suggested the use of gene transfer as a
      possible way to obviate this limitation. Here we have used the lacZ marker gene
      to evaluate methods for gene delivery to ligaments and tendons. Cell cultures
      were established from the following tissues of the New Zealand white rabbit:
      anterior and posterior cruciate ligaments, medial collateral ligament, patellar
      tendon and semitendionsus. In vitro experiments confirmed that these cells were
      very efficiently transduced by an E1- E3- adenoviral vector carrying the lacZ
      gene. Cells derived from ligaments and tendons also proved readily susceptible to
      retroviral transduction and, following transfer of the ned gene, selection in
      G418. To determine whether these cells could be genetically altered in situ, gene
      transfer to the patellar tendons of rabbits' knee joints was attempted using an
      adenovirus for in vivo delivery and a retrovirus for ex vivo delivery. Direct,
      percutaneous injection of the adenovirus resulted in high levels of lacZ
      expression, but this was limited to the area of tendon immediately adjacent to
      the injection site, and preferentially labeled cells in the epitenon sheath. An
      unexpected finding of these studies was the in vivo adenoviral transduction of
      bone cells in areas where the tendon insertion site had been accidentally
      injected. Allotransplantation of tendon fibroblasts into which the lacZ gene had
      been retrovirally introduced led to lacZ expression throughout the body of the
      tendon itself. The genetically altered cells appeared able to migrate from the
      site of injection and to integrate themselves into the crimp pattern of the
      tissue. Both in vivo and ex vivo methods led to gene expression for at least 6
      weeks, which may be long enough for clinical purposes.

PMID- 8986436
TI  - Suicide gene expression induced in tumour cells transduced with recombinant
      adenoviral, retroviral and plasmid vectors containing the ERBB2 promoter.
AB  - In order to exploit the tumour-specific nature of ERBB2 expression for genetic
      prodrug-activation therapy, we have generated recombinant adenoviral, retroviral
      and plasmid vectors containing an expression cassette consisting of the ERBB2
      promoter and herpes simplex virus thymidine kinase coding sequence. In the case
      of the adenoviral vectors, the expression cassette was introduced into the E1 or
      E3 region of the genome. All of the vectors were capable of sensitizing ERBB2
      positive cells to the action of ganciclovir. In contrast to the retroviral and
      plasmid vectors, however, transduction with the adenoviral vectors also resulted
      in sensitization of ERBB2-negative cells to ganciclovir, infection of cell lines
      with a beta-galactosidase expressing adenovirus showed that the sensitizing
      effect was not due to adenoviral infection per as in all but one of the cell
      lines tested. This study demonstrates that the ERBB2 promoter can be used to
      induce ERBB2-dependent sensitization to ganciclovir when in the context of
      retroviral and plasmid vectors. Observations made in this study do, however,
      suggest that adenoviral vectors may not be the ideal system to engineer
      conditional expression, and possible explanation for this phenomenon are
      discussed.

PMID- 8986437
TI  - Gene therapy of spontaneous canine melanoma and feline fibrosarcoma by
      intratumoral administration of histoincompatible cells expressing human
      interleukin-2.
AB  - The production of human interleukin-2 (hIL-2) local to the tumor site by
      engineered histoincompatible cells has been shown in various murine models to
      promote a strong immune response leading to tumor growth inhibition or rejection.
      To assess whether this strategy would be similarly applicable for treatment of
      primary neoplastic cells, two naturally occurring tumors were used as preclinical
      models; the highly metastatic melanoma of the dog and the low metastatic
      fibrosarcoma of the cat. We demonstrate that both cats and dogs when treated by
      tumor surgery, radiotherapy and repeated local injections of xenogeneic Vero
      cells secreting high levels of hIL-2 relapse less frequently and survive longer
      than control animals treated by surgery and radiotherapy alone. Local secretion
      of hIL-2 by the xenogeneic cells is shown to be necessary for the induction of an
      optimal antitumor effect. Moreover, the safety of the procedure was demonstrated
      in both animal models and through extensive toxicological analysis performed in
      rats. These results confirm for the first time to our knowledge the safety and
      therapeutic potential of a gene transfer strategy in animals with spontaneous
      metastatic and nonmetastatic tumors.

PMID- 8986438
TI  - Laboratory and clinical studies in support of cystic fibrosis gene therapy using
      pCMV-CFTR-DOTAP.
AB  - The first phase I study of cystic fibrosis gene therapy using cationic liposomes
      to deliver the cystic fibrosis conductance regulator gene to the nose reported
      partial and transient correction of the nasal transepithelial ion transport
      defect, While encouraging, further improvements will be required if this form of
      treatment is to be of therapeutic value. We tested a new formulation, pCMV-CFTR
      DOTAP. The complex is stable for 10 days and effective at correcting the
      electrophysiological deficit in the trachea of CF mutant mice at 8 or 9 days
      after intratracheal instillation. Reliable protocols for consistent detection of
      as few as 10 molecules of CFTR mRNA and DNA in nasal brushing samples are
      described, Both vector and DNA have been produced to Good Manufacturing Practice
      standard, Nasal potential difference measurements developed at the National Heart
      and Lung Institute to assess the CFTR ion channel activity in CF patients
      replicated well at the Scottish Adult Cystic Fibrosis Service. The SPO
      fluorescence assay for halide ion conductance in nasal brushings has also been
      tested. These establish baseline conditions in the Scottish CF cohort from which
      evidence for correction can be judged under clinical trial conditions. These
      studies formed the basis for regulatory approval of a randomised, placebo
      controlled double-blind phase I research study.

PMID- 8986439
TI  - A stable cell line carrying adenovirus-inducible rep and cap genes allows for
      infectivity titration of adeno-associated virus vectors.
AB  - Adeno-associated virus (AAV) vectors are being developed for in vivo and ex vivo
      gene transfer to human cells. At present, widespread usage of AAV vectors is
      limited primarily by difficulties in generating recombinant virions on a scale
      sufficient for in-depth preclinical and clinical trials. However, recent work in
      several laboratories suggests that this technical obstacle should be overcome in
      the near future. As a result, it can be anticipated that the interest in AAV
      vectors will expand, Thus, it becomes important to develop assay systems that
      will permit accurate quantification of the infectivity of AAV vectors derived
      from a variety of sources. We have developed an assay using a cell line that
      expresses AAV helper functions (rep and cap) upon induction by adenovirus
      infection. This assay system is based on the replication of input rAAV genomes
      rather than transgene expression (transduction). Thus, infectivity titrations in
      this system yield an estimation of rAAV infectious particles irrespective of the
      promoter or transgene present in the vector genome. Moreover, this assay method
      is more sensitive than conventional methods being used in other laboratories.

PMID- 8986440
TI  - Efficacy of a peptide-based gene delivery system depends on mitotic activity.
AB  - We have developed and tested a transfection compound based on synthetic peptides.
      It consists of a 12 amino acid DNA binding peptide (P2) with an alkyl group added
      to the aminoterminus (P2lip) and a peptide derived from the hemagglutinin protein
      (HA). The components aggregate spontaneously to particles that proved to be an
      efficient, easy to use and chemically stable transfection compound. With this
      system we found a marked correlation between transfection efficiency and mitotic
      activity. Cells that are allowed to perform a mitosis after exposure to either
      DNA-P2lip/HA or DNA-cationic liposome complexes are transfected much more
      efficiently than cells arrested in the cell cycle. In search of an explanation
      for this phenomenon we studied transport of plasmid DNA across the nuclear
      membrane. Plasmid DNA injected into the cytoplasm of quiescent human fibroblasts
      is not expressed, in contrast to DNA injected into the nucleus. FISH analysis
      showed that the plasmid DNA is not transported into the nucleus efficiently.
      Similarly, DNA-P2lip/HA complexes are readily taken up by both proliferating and
      nonproliferating cells, but do not readily penetrate the nuclear membrane. We
      conclude that delivery of plasmid DNA to the cytoplasm is not sufficient for
      transfection of eukaryotic cells. The nuclear membrane is apparently an important
      barrier. This explains why a mitotic event is required for efficient transfection
      with the currently available transfection systems. The implications for the
      further development of transfection compounds for use in vivo, where
      nonproliferating cells are often the target, are discussed.

PMID- 8986441
TI  - Investigation of alternative prodrugs for use with E. coli nitroreductase in
      'suicide gene' approaches to cancer therapy.
AB  - The most commonly employed 'suicide' gene/prodrug system used in cancer gene
      therapy is the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir system.
      We have examined the efficacy of an alternative approach utilising the E. coli
      nitroreductase B enzyme with CB1954 and a variety of other prodrugs. V79 cells
      transfected with a nitroreductase expression vector were up to 770-fold more
      sensitive to CB1954 than control non-expressing cells. In general other prodrugs
      which were found by HPLC to act as substrates for purified E. coli nitroreductase
      also exhibited increased cytotoxicity against the nitroreductase-expressing
      cells, although this correlation was not absolute. In particular nitrofurazone
      (97-fold) and additional aromatic nitro-compounds (nine- to 50-fold) showed a
      large differential whereas the quinones and the antimetabolite, B-FU, were less
      effective (< three-fold). The results support the possibility of using
      nitroreductase and CB1954 for 'suicide gene' therapy and in addition suggest that
      alternative prodrugs, such as nitrofurazone, warrant further investigation in
      this novel approach.

PMID- 8986442
TI  - Partial regression, yet incomplete eradication of mammary tumors in transgenic
      mice by retrovirally mediated HSVtk transfer 'in vivo'.
AB  - Mice transgenic for the activated rat neu oncogene under the control of the mouse
      mammary tumor virus long terminal repeat (MMTV-LTR) (neu+ mice), develop breast
      tumors in 100% of cases. We have previously reported that double transgenic mice
      obtained from crossing neu+ mice with mice transgenic for the herpes simplex
      virus thymidine kinase (HSVtk) gene can be used as a suitable model to test the
      'suicide gene' strategy for mammary tumor gene therapy in vivo. In the present
      study, we evaluated the efficacy of the HSVtk/ganciclovir (GCV) system in the
      neu+ mice by inoculating cells producing a retroviral vector bearing the HSVtk
      gene in the mammary tumors on one side of the animals, and comparing their weight
      with that of the contralateral tumors, after systemic GCV administration. A
      statistically significant effect of this therapy was clearly seen (P < 0.001) but
      complete eradication of the tumors could not be achieved. This was not due to the
      inefficient delivery of GCV, as no HSVtk expression was detected in the residual
      tumors, but could be related to the low transduction efficiency (< 10%) and to
      inability of the 'bystander effect' (probably due to the absence of functional
      gap-junctions among mammary tumor cells) to kill nontransduced neoplastic cells.
      These data suggest that results obtained by in vivo models using transplanted
      tumor cell lines as targets for gene therapy might not be immediately
      transferable to spontaneously arising tumors in animals or humans.

PMID- 8986443
TI  - Xanthurenic acid derivative formation in the lens is responsible for senile
      cataract in humans.
AB  - BACKGROUND: The tryptophan degradation pathway leads to NAD production via 3
      hydroxykynurenine. Kynurenine aminotransferase (KAT) transforms 3
      hydroxykynurenine into xanthurenic acid. In this study, we measured the activity
      of KAT in human lenses and studied the consequences of xanthurenic acid formation
      METHODS: KAT activity was determined by the method of Tobes. Fluorescence
      spectroscopy and SDS-PAGE were used for the protein studies. Thin-layer
      chromatography and infrared and fast atom bombardment spectrometry were used for
      substance characterization. RESULTS: The KAT activity was detected in senile
      cataratous lenses, but was absent in the young lenses. Xanthurenic acid at
      physiological pH exists in equilibrium with its tautomeric form reported by us as
      oxo-xanthurenic acid (OXA), which is oxidized to di-oxoxanthurenic acid (DOXA), a
      naphthoquinone-like substance. The incubation of DOXA with crystallins in a
      solution of physiological pH led to crystallin crosslinking and formation of
      conjugates with glutathione. CONCLUSIONS: Xanthurenic acid is formed in human
      lenses. Its tautomerization and oxidation leads to a naphthoquinone-like
      substance, DOXA. DOXA provoked formation of conjugates with glutathione and
      crosslinking of crystallins. Thus, KAT activity seems to be the initial event in
      senile cataract formation in humans.

PMID- 8986444
TI  - Predictive factors for response to medical therapy in bacterial ulcerative
      keratitis.
AB  - BACKGROUND: Fifty-four consecutive cases of culture-positive bacterial ulcerative
      keratitis presenting at a major university hospital were reviewed to identify
      factors predictive of response to medical therapy for bacterial ulcerative
      keratitis (BUK). METHODS: Eleven patients (20%) failed medical therapy (defined
      as the need for surgical intervention or cyanoacrylate gluing). Using
      multivariate logistic regression, the following variables were evaluated: (1)
      predisposing ocular factors (e.g., contact lens wear), (2) pre-existing ocular
      diseases, (3) ulcer size, and (4) the number of topical ocular medications used
      at the time of presentation. RESULTS: We noted certain factors to be potentially
      predictive of medical therapy outcome. The average size of the ulcer at the time
      of presentation was 4.4 +/- 2.4 mm in the failure group but only 2.5 +/- 1.9 mm
      for the success group (P = 0.027). In addition, patients in the medical failure
      group used more topical ocular medications at the time of presentation (P =
      0.0075). Further analysis of the individual topical ocular medications revealed
      that the use of corticosteroids was higher in the failure group (56% vs 12%, P =
      0.0005 by Fisher's exact test). Other factors such as patient age, the type of
      organism(s), and the time elapsed between the onset of symptoms and the beginning
      of definitive therapy were not statistically significant. CONCLUSION: In this
      population, ulcer size at the onset of antibacterial treatment and the use of
      certain ocular medications, specifically corticosteroids, were significant
      predictive factors for failure of medical therapy for BUK.

PMID- 8986445
TI  - Cryopexy in primary rhegmatogenous retinal detachment: a risk factor for
      postoperative proliferative vitreoretinopathy?
AB  - PURPOSE: To evaluate the role of cryopexy in the stimulation of postoperative
      proliferative vitreoretinopathy (PVR) in primary rhegmatogenous retinal
      detachment. MATERIALS AND METHODS: A series of 595 eyes of 554 patients with
      primary rhegmatogenous retinal detachment, referred before any failed surgery,
      were prospectively evaluated. Univariate and multivariate statistical analyses of
      the data were conducted. RESULTS: The incidence of postoperative PVR in relation
      to the methods used for retinopexy was dependent on the types and anatomy of
      retinal breaks associated with retinal detachment. The incidence of postoperative
      PVR was nil in retinal detachments due to atrophic holes in lattice, oral
      dialyses, and macular holes, regardless of the retinopexy methods. Postoperative
      PVR occurred solely in retinal detachments due to horseshoe tears (incidence
      4.42%), paravascular tears of the postequatorial region (18.18%), and giant tears
      (24.6%) (P < 0.00001). The incidence of postoperative PVR was 0.5% in eyes with
      horseshoe tears with mobile posterior edges vs 9.72% in eyes with horseshoe tears
      with curled posterior edges, regardless of the retinopexy methods (P < 0.00001).
      In retinal detachments due to horseshoe tears with mobile posterior edges the
      incidence of postoperative PVR (0.5%) was not influenced by the retinopexy
      methods. In contrast, in retinal detachments due to horseshoe tears with curled
      posterior edges the incidence of postoperative PVR was higher in eyes managed
      with cryopexy (14.77%) than in eyes managed with laser retinopexy (1.78%) (P <
      0.02). In retinal detachments due to giant tears the incidence of postoperative
      PVR was not statistically significantly greater in eyes managed with cryopexy
      (33.3%) than in eyes managed with laser retinopexy (15.6%). In tears 180 degrees
      and over in size, however, the incidence of postoperative PVR was significantly
      higher in eyes managed with cryopexy (9/11 eyes) than in eyes managed with laser
      retinopexy (5/17 eyes) (P = 0.006). CONCLUSIONS: Cryopexy is not a stimulating
      factor for postoperative PVR in primary rhegmatogenous retinal detachments due to
      atrophic holes in lattice, oral dialyses, macular holes, or horseshoe tears with
      mobile posterior edges. In contrast, cryopexy probably is a stimulating factor
      for postoperative PVR in retinal detachments due to horseshoe tears with curled
      posterior edges or to retinal tears 180 degrees and over.

PMID- 8986446
TI  - Optic disc morphology in "age-related atrophic glaucoma".
AB  - BACKGROUND: This study was performed in order to evaluate whether, in primary
      open-angle glaucoma (POAG), patients with a different degree of fundus
      tessellation vary in optic disc morphology and level of intraocular pressure.
      METHODS: Color stereo optic disc photographs of 562 patients with POAG and a
      myopic refractive error of less than -8 diopters were morphometrically examined.
      According to the degree of fundus tessellation, the total group was divided into
      a tessellated subgroup (n = 256) and a nontessellated subgroup (n = 306), both
      matched for neuroretinal rim area and refractive error. RESULTS: In the
      tessellated subgroup, as compared to the nontessellated subgroup, the mean
      maximal intraocular pressure values were significantly lower, the parapapillary
      atrophy was significantly larger, the optic cup was significantly more shallow,
      frequency of disc hemorrhages was lower, the mean visual field defect was
      significantly more marked, and patient age was significantly higher. Within the
      whole study group, the degree of fundus tessellation increased significantly (P <
      0.005) with decreasing mean maximal intraocular pressure, decreasing optic cup
      depth, and increasing degree of parapapillary atrophy. In the subgroups with the
      highest degree of fundus tessellation, parapapillary atrophy was the greatest and
      the mean maximal intraocular pressure was the lowest compared to other subgroups.
      CONCLUSION: At the low-pressure end of POAG, marked fundus tessellation is
      associated with large parapapillary atrophy, shallow disc cupping, mostly
      concentric emaciation of the neuroretinal rim, and high patient age. The results
      suggest a distinct subtype of POAG in older patients with relatively low
      intraocular pressure leading to a mainly diffuse atrophy of the optic nerve.

PMID- 8986447
TI  - Optic disc morphology in juvenile primary open-angle glaucoma.
AB  - BACKGROUND: The aim of the study was to evaluate whether, in primary open-angle
      glaucoma (POAG), patients younger than 40 years differ in optic disc morphology
      from patients older than 40 years. METHODS: Out of a total group of 419 patients
      with POAG, we formed and compared two subgroups, one consisting of 37 patients
      with an age of less than 40 years, the other composed of 382 patients with an age
      equal to or more than 40 years. Both subgroups were matched for neuroretinal rim
      area. We examined the optic disc morphometrically using stereo disc photographs.
      RESULTS: The younger subgroup, as compared to the older subgroup, showed deeper
      and steeper optic disc cupping, concentric emaciation of the neuroretinal rim, a
      significantly smaller area of parapapillary atrophy, and significantly higher
      maximal and minimal intraocular pressure measurements (P < 0.001). The size and
      shape of the optic disc and the diameter of the retinal vessels at the optic disc
      border did not vary significantly. CONCLUSIONS: In POAG, patients younger than 40
      years differ in optic disc morphology from patients older than 40 years. The
      younger patients with POAG have high minimal and maximal intraocular pressure
      readings and an optic disc morphology with deep and steep cupping, concentric
      loss of neuroretinal rim, and an almost unremarkable parapapillary atrophy. POAG
      in patients under 40 represents chronic high-pressure open-angle glaucoma with
      mainly diffuse optic nerve damage.

PMID- 8986449
TI  - Electrolytes in the cornea: a therapeutic challenge.
AB  - BACKGROUND: Reported here are the results of electrolyte measurements in
      different layers of 70 apparently normal human corneas. METHODS: Samples were
      examined by energy-dispersive X-ray analysis under calibrated conditions in a
      scanning electron microscope. The method allows the simultaneous quantitative
      analysis of, among others, sodium (Na), chloride (Cl), phosphorus (P) and
      potassium (K). The results are related to the dry weight of the analyzed samples.
      Four distinct layers, subepithelium, middle stroma, posterior stroma and
      Descemet's membrane, were analysed in each cornea. RESULTS: In the middle stroma
      we found concentrations of: sodium 0.609 +/- 0.13, chloride 0.557 +/- 0.115,
      potassium 0.058 +/- 0.02 and phosphorus 0.038 +/- 0.01 (mol/kg dry weight)
      [corrected]. CONCLUSION: The collation of normal electrolyte concentrations
      provides reference values for future studies on changes of the corneal
      electrolyte composition in diseased or injured eyes. The electrolyte composition
      of rinsing fluids or eye drops should be adjusted to that of the corneal stroma.
      Phosphate buffer, for example, is not a good vehicle for topical eye treatments
      and should be replaced by organic buffering systems.

PMID- 8986448
TI  - Collagen synthesis in lens epithelial cells on capsules containing intraocular
      lens implants in rabbits: immunolocalization of prolyl 4-hydroxylase.
AB  - BACKGROUND: We evaluated ultrastructurally the presence and distribution of lens
      epithelial cells and extracellular matrix on the posterior capsule after
      implantation of a silicone or a polymethyl-methacrylate (PMMA) intraocular lens
      (IOL) in rabbits. The immunolocalization of prolyl 4-hydroxylase, an enzyme
      involved in procollagen synthesis, was also examined in such cells. METHODS:
      Anesthetized adult albino rabbits (n = 12) underwent phacoemulsification and
      aspiration (PEA) of the crystalline lens and implantation of a silicone or a PMMA
      IOL into the capsular bag of one eye. They were killed by an intravenous overdose
      of pentobarbital sodium. The lens capsules were processed for transmission
      electron microscopy and for immunohistochemical detection of the beta-subunit of
      prolyl 4-hydroxylase. RESULTS: Ultrastructurally, lens epithelial cells on the
      posterior capsule evidenced an accumulation of collagenous extracellular matrix.
      Prolyl 4-hydroxylase immunoreactivity was detected in the cytoplasm of cells
      distributed on the capsules. CONCLUSION: Lens epithelial cells are involved in
      the production of collagenous matrix on lens capsules after PEA and implantation
      of IOL, resulting in a fibrotic process of the lens capsule.

PMID- 8986450
TI  - Efficacy of iontophoresis in the rat cornea.
AB  - BACKGROUND: Iontophoresis can enhance penetration of drugs into tissues. We
      examined the extent of penetration of gentamicin into the cornea of rats during
      iontophoresis and the effect of varying the concentrations of gentamicin, the
      duration of iontophoresis and the current densities during iontophoresis.
      METHODS: Eight groups of rats underwent corneal iontophoresis using gentamicin
      dissolved in agar. Low and high concentrations of gentamicin were used, as well
      as low and high current densities and long and short durations of iontophoresis.
      Control groups received topical or subconjunctival gentamicin, topical saline
      solution and mock iontophoresis with the agar-gentamicin mixture. The Mann
      Whitney test was used for statistical evaluation. RESULTS: Highly bactericidal
      concentrations of gentamicin were obtained in all the iontophoresis-treated
      corneas. The high concentration compared to the low concentration of gentamicin
      in agar significantly increased the concentration of gentamicin in the corneas,
      as did the longer duration of iontophoresis. However, higher current intensity
      did not significantly enhance the drug concentration in the cornea. CONCLUSION:
      Iontophoresis with a concentrated gentamicin-agar mixture may provide a rapid
      increase of gentamicin levels in the cornea.

PMID- 8986451
TI  - Detection of antibodies to Borrelia species among patients with confirmed
      sarcoidosis in a region where Lyme disease is nonendemic.
AB  - BACKGROUND: Lyme disease is a multisystemic disorder caused by the spirochete
      Borrelia burgdorferi, while sarcoidosis is a multisystemic granulomatous disease
      of unknown etiology. The purpose of this study was to evaluate the relationship
      between Lyme disease and sarcoidosis. METHODS: We examined the seroprevalence of
      antibody to Borellia species in patients with sarcoidosis. We performed the
      enzyme-linked immunosorbent assay, using three Japanese Borrelia species in
      addition to B. burgdorferi, and dotblot analysis using purified Borrelia-specific
      proteins in 38 patients with histopathologically confirmed sarcoidosis and 80
      healthy controls. RESULTS: Two patients (5.3%) were positive for antibodies to
      Borrelia species according to one or both assays, and one (1.2%) healthy control
      was positive. In both patients it was suspected that Borrelia infection had
      developed prior to the development of sarcoidosis. CONCLUSION: Borrelia species
      were thought not to be responsible for the development of sarcoidosis in a
      nonendemic region in Japan. Since clinical manifestations of Lyme disease share
      certain similarities with those seen in sarcoidosis, ophthalmologists should be
      aware of the need to differentiate between the two diseases and the need for
      prompt treatment in each case.

PMID- 8986452
TI  - Antioxidant effects of calcium antagonists on rat myocardial membrane lipid
      peroxidation.
AB  - We studied the antioxidant effects of nine calcium antagonists (nisoldipine,
      benidipine, nilvadipine, felodipine, nicardipine, nitrendipine, nifedipine,
      verapamil, and diltiazem) by means of rat myocardial membrane lipid peroxidation
      with a nonenzymatic active oxygen-generating system (DHF/FeCl3-ADP). The order of
      antioxidant potency of these agents was nilvadipine > nisoldipine > felodipine >
      nicardipine > verapamil > benidipine. Their IC50 values (microM) were 25.1, 28.2,
      42.0, 150.0, 266.1, and 420.0, respectively. In contrast, nitrendipine,
      nifedipine, and diltiazem had little inhibitory effect on lipid peroxidation.
      These six calcium antagonists could be divided into four types on the basis of
      their antioxidant mechanisms. Nilvadipine, nisoldipine, and verapamil, which
      showed antioxidant effects both before and after the addition of active oxygen,
      and reduced the dihydroxyfumarate (DHF) auto-oxidation rate, were chain-breaking
      and preventive antioxidants. Felodipine, which showed antioxidant effects both
      before and after exposure to active oxygen and increased the DHF auto-oxidation
      rate, was only a chain-breaking antioxidant. Nicardipine, which showed an
      antioxidant effect only before exposure to active oxygen and reduced the DHF auto
      oxidation rate, was mainly a preventive antioxidant. Benidipine, which showed an
      antioxidant effect only before exposure to active oxygen and had no appreciable
      effect on the DHF auto-oxidation rate, could interrupt the chain reaction of
      lipid peroxidation at the initial step alone. Although these results suggest that
      the antioxidant properties of some calcium antagonists may be beneficial
      clinically in protecting against cellular damage caused by lipid peroxidation,
      further studies are required to establish the antioxidant effects of these agents
      in vivo.

PMID- 8986453
TI  - Neutral endopeptidase inhibition potentiates the effects of natriuretic peptides
      in renin transgenic rats.
AB  - The influence of neutral endopeptidase (NEP) inhibition with (S)-thiorphan on the
      hormonal, renal, and blood-pressure-lowering effects of an infusion of atrial
      (ANP), brain (BNP), and C-type natriuretic peptide (CNP) was evaluated in
      hypertensive transgenic rats (TGR) harboring an additional mouse renin gene
      (TGR(m(Ren2)27)). These TGR possess an activated natriuretic peptide system as
      compared with Sprague-Dawley rats (SDR), used in this study as control. (S)
      Thiorphan significantly decreased blood pressure in anesthetized TGR but not in
      anesthetized SDR during the 60-min infusion period. Exogenously administered ANP
      decreased blood pressure in SDR with no significant effects in TGR after 60 min.
      In contrast, BNP infusion significantly decreased blood pressure in TGR, while
      changes in SDR were not significant. The blood pressure was further decreased
      after combined infusion of ANP and BNP with (S)-thiorphan in TGR. No effect on
      blood pressure was registered during infusion of CNP in either experimental
      group. The plasma levels of ANP, BNP, and cGMP were higher in TGR than in SDR,
      whereas plasma renin activity was lower. Co-administration of ANP, BNP, or CNP
      with the NEP inhibitor (S)-thiorphan potentiated the plasma ANP, BNP, and cGMP.
      Infusion of ANP alone did not affect BNP plasma levels of TGR and vice versa. In
      contrast, CNP infusion increased ANP plasma levels in both TGR and SDR. Renal
      excretion of sodium and cGMP increased after infusion of (S)-thiorphan and ANP or
      BNP in both TGR and SDR. The combination of ANP and (S)-thiorphan had a slightly
      greater effect on urinary excretion of sodium and cGMP in TGR than either
      compound alone, but the effects were more pronounced in SDR than in TGR. Finally,
      infusion of CNP alone and in combination with (S)-thiorphan influenced the
      excretion of sodium and cyclic GMP only slightly. These results indicate that
      inhibition of neutral endopeptidase by (S)-thiorphan potentiates the hemodynamic
      and renal effects of natriuretic peptides ANP and BNP, and to some extent those
      of CNP, in hypertensive TGR and normotensive SDR. In contrast to ANP and BNP,
      infusion of CNP had no effect on the blood pressure in anesthetized TGR or SDR.
      Inhibition of NEP therefore seems to be a promising way to potentiate endogenous
      levels of natriuretic peptides, which may be of therapeutic benefit in
      cardiovascular diseases such as hypertension or heart failure.

PMID- 8986454
TI  - Chronic effect of beta-adrenoceptor blockade on plasma levels of brain
      natriuretic peptide during exercise in essential hypertension.
AB  - Many factors have been reported to stimulate the release of brain natriuretic
      peptide (BNP) as well as atrial natriuretic peptide (ANP). In hypertensive
      patients, however, little is known about whether these factors differ from those
      in normotensive subjects or if they are influenced by antihypertensive treatment.
      We measured the plasma concentrations of BNP and ANP in 12 hypertensive patients
      and examined the chronic effects of beta-adrenoceptor blockade on BNP secretion
      during exercise with a bicycle ergometer. The exercise raised both plasma BNP and
      ANP with concomitant increases in systolic blood pressure, heart rate (HR) and
      plasma norepinephrine (NE) and epinephrine (Epi) before and after treatment.
      Before treatment, the changes in ANP and BNP correlated with that in HR (p <
      0.05). After treatment 4 wk of treatment, the change in ANP correlated with those
      in NE and Epi as well as HR. Multivariate regression analysis indicated that only
      NE was a significant stimulus for ANP secretion during the treatment period. As
      for BNP, HR was the only significant stimulant for its secretion both before and
      after treatment. In essential hypertension, beta-adrenergic receptor blockade
      affected the factors stimulating exercise-induced ANP release but not those
      stimulating BNP release. BNP release, therefore, seems to be stimulated by
      similar but distinct factors from those that stimulate ANP release.

PMID- 8986455
TI  - Combined effects of the angiotensin II antagonist candesartan cilexetil (TCV-116)
      and other classes of antihypertensive drugs in spontaneously hypertensive rats.
AB  - The antihypertensive effects of an angiotensin II antagonist, candesartan
      cilexetil (TCV-116), and other classes of antihypertensive drugs (including a
      calcium antagonist, manidipine; a diuretic, hydrochlorothiazide (HCTZ); an alpha
      blocker, prazosin; and a beta-blocker, atenolol) administered in combination were
      examined in spontaneously hypertensive rats by oral administration daily for 2
      wk. TCV-116 at 1 mg/kg lowered the blood pressure by about 50 and 30 mmHg, 5 and
      24 h after dosing, respectively. The blood pressure was slightly lowered by HCTZ
      at 10 mg/kg, but it was synergistically reduced when HCTZ was given in
      combination with TCV-116. Manidipine at 3 mg/kg lowered the blood pressure by
      about 50 mmHg 1 h after administration. When manidipine was given in combination
      with TCV-116, blood pressure was reduced additively. Prazosin at 1 mg/kg lowered
      the blood pressure by 40 to 50 mmHg 1 h after dosing. When prazosin was given in
      combination with TCV-116, the reduction was intensified more than additively, to
      about 100 mmHg. Atenolol at 50 mg/kg lowered the blood pressure by 10 to 20 mmHg
      5 h after dosing. Even when atenolol was administered in combination with TCV
      116, the reduction in blood pressure was virtually the same as that observed when
      TCV-116 was given alone. TCV-116 and HCTZ had no effect on the pulse rate,
      whereas manidipine and prazosin both increased it, owing to reflex tachycardia,
      and atenolol decreased it. TCV-116 had no effect on the change in the pulse rate
      induced by these antihypertensive drugs and no effect on HCTZ-induced diuresis.
      TCV-116 and HCTZ each caused a significant increase in plasma renin concentration
      (PRC), and prazosin caused a slight elevation. Manidipine had no effect on the
      PRC, whereas atenolol reduced it. Given in combination with TCV-116, these
      antihypertensive drugs had the same effect on the elevated PRC induced by TCV-116
      as they did on the basal PRC when administered alone. These results suggest that
      antihypertensive drugs that cause compensatory activation of the renin
      angiotensin system have more marked antihypertensive activity when given in
      combination with TCV-116, but that there will is no combined effect on the pulse
      rate.

PMID- 8986456
TI  - Different effects of alcohol and salt on 24-hour blood pressure and heart rate in
      hypertensive patients.
AB  - To compare the influences of alcohol and salt intake on 24-h blood pressure (BP),
      we studied short-term effects of repeated alcohol ingestion and dietary salt
      intake in hypertensive patients. Thirty-two Japanese men with mild to moderate
      essential hypertension (54 +/- 1 years old, mean +/- SE) were examined. Sixteen
      patients were given alcohol (1 ml/kg) with dinner for 7 d after a 7-d control
      period with an isocaloric beverage. Another group consisting of 16 age- and
      weight-matched patients consumed a low-sodium diet (25 mmol/d) for 7 d, followed
      by a high-sodium diet (250 mmol/d) for 7 d. Twenty-four-hour BP was measured at
      the end of each period. Average 24-h BP in the alcohol period (137 +/- 4/83 +/- 2
      mmHg) was similar to that in the control period (138 +/- 4/84 +/- 2 mmHg).
      However, BP in the alcohol period was significantly lower in the evening, but
      significantly higher in the morning than that in the control period. Heart rate
      increased for several hours after alcohol ingestion, resulting in a significant
      increase in 24-h heart rate (67 +/- 2 vs. 64 +/- 2 beats/min). Average 24-h BP
      was higher in the high salt period (144 +/- 4/89 +/- 4 mmHg) than in the low salt
      period (135 +/- 3/85 +/- 3 mmHg, p < 0.05). The pressor effect of high salt
      intake was sustained throughout the day and was associated with a decrease in 24
      h heart rate (60 +/- 2 vs. 66 +/- 2 beats/min). In conclusion, short-term
      repeated intake of alcohol may have little effect on average 24-h BP while it
      causes an evening fall and a morning rise in BP, and high salt intake raises BP
      throughout the day. Alcohol consumption increases and salt loading decreases 24-h
      heart rate.

PMID- 8986457
TI  - Restoration of endothelial cell function by chronic cicletanine treatment in Dahl
      salt-sensitive rats with salt-induced hypertension.
AB  - The effects of chronic cicletanine (CICL) treatment on endothelial cell function
      were investigated in Dahl salt-sensitive (Dahl S) rats. Forty-four six-week-old
      Dahl S rats were divided into four groups: i) 10 Dahl S rats fed a low-salt (0.3%
      NaCl) diet and given vehicle, ii) 12 Dahl S rats fed a high-salt (4% NaCl) diet
      and given vehicle, iii) 11 low-dose (10 mg/kg body weight/d) CICL-treated Dahl S
      rats fed a high-salt diet, and iv) 11 high-dose (30 mg/kg body weight/d) CICL
      treated Dahl S rats fed a high-salt diet. The rats were maintained on the
      respective salt regimen for 12 wk and treated with cicletanine for the last 6 wk,
      after which various parameters of endothelial cell function were determined.
      Systolic blood pressure, measured by the tail-cuff method, was reduced
      significantly by high-dose cicletanine (223 vs. 195 mmHg, p < 0.01). Scanning
      electron microscopy revealed that high-dose CICL attenuated endothelial injury in
      the aorta of Dahl S rats. Arterial lesions in the heart and glomerulosclerosis in
      the kidney were significantly reduced by treatment with high-dose CICL. Moreover,
      prostacyclin (PGI2) and prostaglandin E2 (PGE2) generation in the aortic wall was
      significantly increased by 28% (p < 0.005) and by 149% (p < 0.001), respectively,
      by high-dose CICL. Nitric oxide (NO) generation in the aortic walls was
      significantly increased by high-dose CICL (0.38 vs. 15.4 pmol/cm2/30 min, p <
      0.001). This effect was accompanied by a 47% increase in cGMP synthesis in the
      vascular walls. In contrast, the synthesis of PGI2, PGE2, and NO in the kidney
      slices did not differ significantly among the four experimental groups. In
      addition, the generation of vasodilatory substances inversely correlated with the
      score of vascular lesions in the heart and kidney. The results suggested that the
      blood pressure reduction by chronic cicletanine treatment in Dahl S rats is
      associated with an improvement in endothelial cell function. The increased
      release of vasodilatory substances from endothelial cells may contribute to the
      blood pressure reduction and attenuation of vascular injury observed with
      cicletanine treatment.

PMID- 8986458
TI  - Down-regulation by cAMP of angiotensin II type 2 receptor gene expression in PC12
      cells.
AB  - The rat angiotensin II type 2 receptor (AT2-R) gene was isolated, and cis
      regulatory regions in its 5'-flanking area were analyzed. Primer extension and
      RNase protection analyses revealed a single transcriptional initiation site at
      the position 24 bp downstream of the TATA box. The 5'-flanking region of AT2-R
      contained several cis-regulatory elements, such as AP-1, AP-2, C/EBP, NF-1, NF
      IL6, NF-kappa B, and glucocorticoid- and cAMP-responsive elements (CRE). The
      treatment of PC12 cells with dibutyryl cAMP caused a marked decrease (90%) in the
      AT2-R mRNA level, which was blocked by the inhibitor of protein kinase A and did
      not require new protein synthesis. The protein level was also reduced 84% after a
      24-h exposure to cAMP and the binding affinity was unchanged. The half-life of
      the AT2-R mRNA decreased -66% by cAMP as compared with control (18.4 +/- 0.4 h).
      Deletion and mutation analyses of the 5'-flanking region (1.2 Kb) revealed that
      there were one negative (-1,199 to -739) and two positive cis-regulatory regions
      (-739 to -436 and -59 to +45), and that the CRE motif located at -426 repressed (
      23%) the promoter activity of the rat AT2-R gene. The region between -59 and +45
      containing TATA box and AP-2 site accounted for 70% of the promoter activity.
      These findings indicate that the promoter activity of the rat AT2-R gene is
      modulated by several cis-regulatory regions and that cAMP markedly downregulates
      the expression of the AT2-R mainly by inducing AT2-R mRNA destabilization rather
      than CRE-mediated inhibition of the gene transcription. Thus, humoral factors
      that transduce cAMP as an intracellular signal may modulate AT2-R-mediated
      function of Ang II by reducing AT2-R expression.

PMID- 8986460
TI  - Pheochromocytoma-related myocardial damage following delivery.
AB  - We present the case of a 35-year-old woman whose pregnancy was complicated by the
      rare condition of transient pheochromocytoma-related myocardial damage. Short
      duration left ventricular dysfunction was apparently caused by acute non
      transmural myocardial infarction provoked by coronary artery vasospasm rather
      than catecholamine-induced cardiomyopathy. Forty-eight days after onset, a 50 x
      55 x 35 mm tumor was excised and histologically confirmed to be a
      pheochromocytoma.

PMID- 8986459
TI  - Current status of antihypertensive therapy for elderly patients in Japan.
AB  - To assess how elderly Japanese hypertensive patients are treated by specialists,
      we conducted a cross-sectional survey. A total of 1,163 outpatients aged 50 years
      or older were studied. Hypertension was diagnosed in 939 of these patients, and
      827 were receiving drug therapy. The average blood pressure during therapy was
      143 +/- 16/81 +/- 10 mmHg. In patients aged 70 years or older, systolic blood
      pressure during antihypertensive therapy was significantly higher (p < 0.01) and
      diastolic blood pressure was significantly lower (p < 0.01) than the
      corresponding values in those aged 50 to 59 years or 60 to 69 years. The
      calculated mean blood pressures were similar in the different age groups. The
      rate of monotherapy in the patients aged 70 years or older was 58.8%, which was
      significantly higher (p < 0.01) than the rates of monotherapy in the other age
      groups. Calcium channel blockers were prescribed in about 80% of patients,
      irrespective of age or comorbidity. Of the patients receiving calcium channel
      blockers, 43.5% were treated with monotherapy. This rate significantly (p < 0.01)
      increased with advancing age. Diastolic blood pressures were significantly lower
      (p < 0.05) in patients with stroke and in those with ischemic heart disease,
      diabetes mellitus, or dyslipidemia, as compared with patients with no
      comorbidity. Among patients aged 70 years or older, the difference in systolic
      blood pressure between those with ischemic heart disease and those with no
      comorbidity was not significant. Blood pressure in elderly hypertensive patients
      was reduced to a level similar to that in younger patients. The target blood
      pressure was influenced by the presence of comorbidity. Furthermore, specialists
      showed a high preference for the use of calcium channel blockers in the
      management of hypertension.

PMID- 8986461
TI  - Mode of action of FK-506 on protective immunity to Hymenolepis nana in mice.
AB  - FK-506 (Tacrolimus) has been shown to block T cell proliferation in vitro by
      inhibiting the generation of several lymphokines, especially interleukin (IL)-2,
      but little direct evidence is available to support the view that the
      immunosuppressive effects of FK-506 in vivo are mediated by a similar inhibition
      of lymphokine cascade. To investigate the mechanisms of FK-506-induced
      immunosuppression, the effects of FK-506 on cell-mediated immunity to Hymenolepis
      nana were examined in mice. FK-506 administration into BALB/c mice daily at a
      dose of 10.0 mg/kg (but not 5.0 mg/kg) for 5 days caused suppression of
      protective immunity against H. nana challenge infection. During the infection of
      mice with H. nana, IL-2 and interferon (IFN)-gama were produced by mesenteric
      lymph node (MLN) cells with a time course corresponding to that of MLN T cell
      proliferation. These responses were completely suppressed by repeated
      administration of FK-506 for 5 days at a dose of 10.0 mg/kg/day (but not 5.0
      mg/kg/day). In contrast to the effects of FK-506 on IL-2 and IFN-gamma
      productions in MLN, IL-1 and tumor necrosis factor-alpha in the intestinal wall,
      which were enhanced by H. nana infection, were not completely decreased as a
      result of 10.0 mg/kg FK-506 treatment. The reverse transcriptase-PCR revealed
      complete inhibition of IL-2 and IFN-gamma mRNA expression on mesenteric L3T4+
      cells that were induced by H. nana infection, when mice were given 10.0 mg/kg/day
      FK-506 for 5 days. These results strongly suggest that FK-506 affects cell
      mediated immunity in vivo with mechanisms similar to those observed in vitro.

PMID- 8986463
TI  - Fracture healing is a process independent of p53 function.
AB  - We studied the role of the tumor suppressor gene p53 in the process of fracture
      healing using mice with a p53 gene deficiency. Fractures produced in femoral
      shafts of mice without a functional p53 gene (p53-/-) healed as well as those in
      wildtype mice (p53 +/+), and no tumor development was observed at the fracture
      site even after complete bone union. Formation of granulation tissue and
      cartilage, ossification and remodeling into mature trabecular and cortical bone
      showed no abnormalities in p53-/- mice. Apoptotic cells were found to be sparse
      in the ossifying zone of the fracture callus using in situ DNA nick end-labeling
      in mice of both genotypes, without any significant difference. These results
      indicate that apoptosis in fracture healing, even if it does play a significant
      role, occurs through a p53-independent pathway.

PMID- 8986462
TI  - Interactions between tissues engaged in wound repair and skeletal muscle
      regeneration.
AB  - Enhanced accumulation of granulation tissue in a wound healing model was observed
      in the presence of regenerating skeletal muscle. This study characterized the
      tissue accumulated in the normal wound healing and regeneration-adapted models.
      DNA, RNA, total protein, collagen, and noncollagen protein content, and
      protein:DNA and noncollagen protein:collagen ratios were determined using
      standard methods. DNA did not differ; but RNA increased and total protein
      decreased compared to early granulation tissue. Mean protein: DNA ratio was lower
      in regeneration-associated granulation tissue compared to age-matched normal and
      early granulation tissue. Collagen was reduced and noncollagen protein was
      increased in tissue surrounding regenerating muscle, yielding an elevated
      noncollagen:collagen ratio. The relative cellularity of granulation tissue was
      enhanced and collagen deposition potentially reduced, when accompanied by
      regeneration. Factors from a regeneration environment can interact with cells
      engaged in wound repair and potentially alter their behavior.

PMID- 8986464
TI  - Low dose sequential methotrexate and 5-fluorouracil administration is effective
      and safe as neo-adjuvant chemotherapy in oral cancer.
AB  - We report on the effects and complications associated with low dose sequential
      methotrexate (MTX) and 5-fluorouracil (5-FU) (MF therapy) as neo-adjuvant
      chemotherapy in oral cancer. The oral cancer of 19 patients was treated as
      follows: MTX (75 mg/body) was administrated by intravenous infusion for 1 hour,
      followed by 5-FU (500 mg/body) intravenous infusion for 2 hours, on Day 1. MTX
      (75 mg/body) intravenous infusion for 1 hour on Day 4. and parenteral dose of
      leucovorin on Day 2 and Day 5. A complete response was attained in one patient
      and a partial response in 11 patients. Complications observed were: increased
      serum transaminase levels (4), leucopenia (3). nausea or vomiting (4). anemia
      (1). The MF therapy of 2-8 courses was performed weekly or every 2 weeks. The
      volume in tumors of all cases decreased. Toxicity was extremely mild and
      radiotherapy or operation could be added sequentially without increased toxicity.
      These results suggests that MF therapy is effective and safety as neo-adjuvant
      chemotherapy before radiation and surgery for patients in oral cancer.

PMID- 8986465
TI  - A mouse model of herpes simplex virus encephalitis: diagnostic brain imaging by
      magnetic resonance imaging.
AB  - Herpes simplex virus encephalitis is a severe sporadic encephalitis in man with
      high mortality and morbidity. A critical step in the establishment of therapy is
      early diagnosis. Magnetic resonance imaging is a noninvasive, accurate diagnostic
      test for the detection of central nervous system disease. In an effort to monitor
      morphological changes in vivo we present a new diagnostic neuroimaging model of
      experimental herpes simplex virus encephalitis. A mouse model of herpes simplex
      virus encephalitis was used. 40 SJL mice were intranasally inoculated with an
      infectious dose of wild-type strain HSV-I F. Morphological abnormalities were
      studied by cranial magnetic resonance imaging (MRI). These findings were
      correlated with sequential neuropathological studies. 95% of animals developed
      cerebral abnormalities on MRI. resembling human HSVE. Areas of increased signal
      intensity on T2-weighted sequences and focal pathological contrast enhancement
      were mostly found in the frontal and temporal lobes and thalamic and cerebellar
      regions. All animals with MRI abnormalities had neuropathological signs of
      neuronal degeneration and reactive astrocytosis in corresponding regions. The
      described monitoring system offers a new approach for studies on neurovirulence
      and therapeutic strategies.

PMID- 8986466
TI  - Investigation of the influence of theophylline feeding on total, free, short
      chain acyl and long-chain acyl carnitine levels in skeletal muscle and liver of
      rats.
AB  - L-carnitine, the obligate fatty acyl carrier across the inner mitochondrial
      membrane, is sensitive to biochemical changes that alter lipid metabolism. The
      present study describes the effects of oral theophylline on L-carnitine
      concentrations in the skeletal muscle and the liver of rats. A significant rise
      in total, free and long-chain acyl carnitine concentrations was observed in the
      skeletal muscle but not in the liver. The increases observed after the first week
      of theophylline feeding returned to the control concentrations after fifth week
      despite the continuation of treatment. The observed changes in the skeletal
      muscle may be due to a) increased acyl carnitines that are formed as a
      consequence of enhanced fatty acid mobilization and b) increased L-carnitine
      uptake by the tissue.

PMID- 8986467
TI  - The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in
      the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the
      new vitamin C infusion treatment with a volunteer CFS patient.
AB  - A series of publications from our laboratory have indicated that the practice of
      megadose vitamin C drip infusion treatment enhanced the activity of endogenous
      glucocorticoids in such a way as to improve the clinical course of allergy and
      autoimmune disease-a disease entity that is known to respond to the therapeutic
      effect of glucocorticoids. The present paper represents an extention of our
      vitamin C studies, and intends to investigate the problem whether or not chronic
      fatigue syndrome (CFS), an acquired immunodeficiency disease, can also be counted
      as one of the candidate diseases for the vitamin C infusion treatment. We
      prepared two kinds of vitamin C infusion sets for the clinical use: the
      dehydroepiandrosterone-annexed vitamin C infusion set (the new set) and the annex
      free vitamin C infusion set (the old set). The new set was expected to enhance
      the endogenous activities of both glucocorticoids and gonadal steroids. We
      followed the clinical course of a male CFS patient using the old and new vitamin
      C infusion sets, and with and without the oral intake of erythromycin and
      chloramphenico. Results obtained are as follows: a) the observation period of a
      study subject covered a period of August 1995 to May 1996. Combination of
      pneumonia signs and dermatomyositis signs marked the onset of his CFS. b) Old
      infusion treatment together with the short term antibiotics treatment was found
      effective for the control of pneumonia in the first stage of the disease (from
      August to October, 1995). c) Signs of pneumonia recurrence gradually became
      eminent in the second stage of disease (from November, 1995, to January, 1996) in
      spite of the moderate frequency of the old treatment together with stepwise
      prolongation of the antibiotics treatment. d) The alternate practice of the old
      and new infusion treatments together with the long-term antibiotics treatment, as
      conducted in the 3rd stage of disease (from February to May, 1996) led to
      substantial extinction of pneumonia signs (leucocytosis, tachycardia etc). e) The
      practice of the new infusion treatment markedly increased the excretion of both
      17-ketosteroids and 17-hydroxycorticosteroids in the urine. Evidence was also
      available to indicate that the dehydroepiandrosterone annex was converted to
      testosterone, which in turn made a contribution to the control of CFS. f) The
      immunological survey of lymphocyte subsets including NK cell percent failed to
      find a coherent change in a study subject with CFS. In conclusion, the above
      results could be taken as evidence to indicate that the new vitamin C infusion
      treatment effectuates the clinical control of CFS by fortifying the endogenous
      activities of both cortisol and testosterone. The significance of parallelism
      between pulmonary infection and CFS, as observed in the clinical course of the
      test subject, was discussed in the light of the focal infection theory of
      nephritis.

PMID- 8986468
TI  - The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in
      the clinical control of chronic fatigue syndrome (CFS). II. Characterization of
      CFS patients with special reference to their response to a new vitamin C infusion
      treatment.
AB  - This study is a counterpart of the pilot study on the clinical management of
      chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and
      the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and
      without oral intake of erythromycin and chloramphenicol. We were motivated to
      start this clinical study by 2 reasons: i) we have made a success in the clinical
      management of autoimmune disease and allergy by use of the old megadose vitamin C
      infusion treatment, and we therefore took up CFS as a good candidate for vitamin
      C infusion treatment; ii) In 1995, we received a total of 313 chronic pneumonia
      patients whose clinical course showed a good fitness to the criteria of CFS. We
      assessed the nature of the disease by investigating the clinicoepidemiological
      aspect of our patients on the one hand and the response of the disease to both
      the old and new vitamin C infusion treatments with and without the use of 2
      antibiotics on the other hand. Results are summarized as follows: a) the analysis
      of the medical records of our outpatients revealed that chronic type pneumonia
      epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its
      extinction by the end of May 1996. The patient population contained no patients
      under 15 years of age, and showed a distinct female predominance in the patient
      number (207 females versus 106 males). In 1995, we also experienced a simple cold
      epidemic with its onset of January 1995 (162 males and 224 females). The majority
      of simple cold patients were under 25 years of age in both sexes. b) A chronic
      type pneumonia patient was distinguished from a simple cold patient in 2
      respects: firstly the former required prolonged medical care (over 1 month)
      resulting in an incomplete cure and return to medical care upon the recurrence of
      disease, whereas the latter required short-term medical care (mostly within 1
      week) ending up with complete cure. Secondly, the former required the long term
      use of 2 antibiotics (erythromycin and chloramphenicol) together with regular
      practice of the old and new vitamin C infusion treatments for disease control,
      whereas the latter recovered from the disease after the short time use of a set
      of conventional cold remedies. c) The clinical manifestations of our chronic
      pneumonia patients showed good fitness to the criteria of CFS. d) CFS was
      distinguished from autoimmune disease-allergy complex by the method of clinical
      control: the former required the long-term use of 2 antibiotics together with
      regular practice of the old and new vitamin C infusion treatments, whereas the
      latter was controllable by the single use of the old vitamin C infusion
      treatment. e) The combined use of the old and new vitamin C infusion treatments
      rather than the single use of the old vitamin C infusion treatment was more
      effective for the control of CFS-a finding which suggests that deficient
      activities of both endogenous glucocorticoid and endogenous androgen in a CFS
      patient are somehow related to the genesis and further development of CFS. f)
      Evidence was available to indicate that the sole use of the new vitamin C
      infusion treatment may induce a state of gonadal steroid excess together with
      various other problems in the recipient. The maintenance of a good balance
      between the old vitamin C infusion set (glucocorticoid-inducer) and the new
      vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in
      their use was of prime importance for the successful control of CFS. g) The
      historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is
      discussed in the light of the new infection concept.

PMID- 8986469
TI  - Cigarette smoking and vaginal atrophy in postmenopausal women.
AB  - The atrophy of the vaginal epithelium was studied clinically and cytologically on
      vaginal smears of 1638 healthy postmenopausal female non smokers and 531 healthy
      postmenopausal smokers (over 30 years), with a mean age of 58 years. A very
      strong statistically significant difference (p < 0.0001) in the atrophical
      vaginal changes between smokers and nonsmokers to the disadvantage of the
      smokers. Also a very statistically significant association (p < 0.0001) was
      observed between the cytological expression of the vaginal atrophy and duration
      at menopause of the non-smokers but no association in the cases of the smokers.
      Another important result of this study was that the smokers women had an early
      menopause (p < 0.0001), on average by 2 years sooner (mean age 48.5 years) than
      non-smokers (mean age 50.5 years). These results suggest that cigarette smoking
      has an effect on the vaginal squamous epithelium, increasing the atrophical
      changes and causing early menopause by mechanisms, some of which remain unclear.

PMID- 8986470
TI  - Effects of acridines on bacterial plasmid replication and endotoxin.
AB  - Different amino- and imino-acridines were systematically synthesized. The
      antibacterial, antiplasmid, antimotility and endotoxin complexing effect of
      acridines were studied, when antibacterial effect of the compounds was compared
      on E. coli. Aminoderivatives were more active than imino-acridines. The N-heptyl
      9-imino-acridine was able to select lon minus mutants in the E. coli culture,
      however, the other acridines tested were ineffective in this respect. The
      iminoacridines inhibited the motility of Proteus vulgaris more effectively than
      aminoderivatives. The antimotility action of the acridines was also dependent on
      the ionic content of the media. The antiplasmid effect was measured on an F-prime
      plasmid of E. coli LE140 strain. Iminoacridines had a more powerful antiplasmid
      effect than the amino-substituted derivatives. The majority of the compounds
      inhibited the intercellular plasmid transfer from E. coli. Kmr donor to a Na
      azide resistant recipient. In this test the aminosubstituted derivatives were
      shown to be more effective inhibitors of conjugation than the imino-substituted
      compounds. Endotoxin formed complexes with N-butylamino. N-propy-lamino and
      imidoderivatives. However, complex formation of N-ethyl-, N-heptyl-, N
      diethylaminoethyl- and N-diethylamino-propyl-acridines were different.
      Correlations between molecular orbitals and the antibacterial effects are also
      discussed.

PMID- 8986471
TI  - Lectin binding as a prognostic indicator in gestational trophoblastic diseases
      (GTD).
AB  - Gestational Trophoblastic Diseases (GTD) is a group of hyperproliferative
      conditions of the placenta. Very often these can be fatal or recurrent.
      Presently, no reliable marker is available apart from serum beta HCG levels to
      identify tumours with a higher aggressive nature, the reduction pattern of the
      serum beta HCG levels indicating persistence of the disease. This causes a delay
      of nearly 12-16 weeks in deciding on chemotherapy. In this study, the potential
      of Jack fruit lectin (JFL) binding as a quick and cheap method of assessing the
      aggressiveness of the disease immediately after evacuation was evaluated. A
      significantly higher intensity of lectin binding was noticed in GTD when compared
      to gestational age related normal placentae. Persisting tumour lesions generally
      showed intense, diffuse and granular lectin binding and showed significant
      cytological atypia. The lectin binding score showed close correlation with the
      regressing pattern of serum beta HCG but not with the initial levels of beta HCG,
      indirectly pointing to its potential in identifying lesions with high risk of
      persisting disease. Hence evaluation of the lectin binding characteristics of the
      lesion immediately after evacuation will be of help in following up these
      patients closely and planning therapy.

PMID- 8986472
TI  - Cigarette smoking as a risk factor for intraepithelial lesion of the cervix
      uteri.
AB  - Cervical intraepithelial lesions were diagnosed cytologically, and confirmed
      histologically in 328 patients from 1990 to 1996 at the University Hospital of
      Heraklion. The women were grouped according to the grade of the cervical
      intraepithelial lesion as low grade cases (LSIL) on high grade cases (HSIL)
      (Bethesda classification). They were also grouped according to their smoking
      status as non-smokers or smokers. A very strong statistically significant
      difference (p < 0.0001) in the incidence of the disease between non-smokers and
      smokers was found, to the disadvantage of smokers. Also a very statistically
      significant (p approximately 0.001) association was found between the number of
      cigarettes per day, duration of exposure (years of use) and the grade of cervical
      intraepithelial lesion. Our results indicate that cigarette smoking is a risk
      factor in the development of cervical intraepithelial lesions and possibly
      cervical squamous cancer. Further studies are required to prove this hypothesis
      and to document the biological plausibility of this relationship.

PMID- 8986473
TI  - Severe community-acquired pneumonia: what do we need to know to effectively
      manage patients?

PMID- 8986474
TI  - Prognosis factors in severe community-acquired pneumonia: a step forward.

PMID- 8986475
TI  - Aspergillosis in the ICU: the glass half-empty?

PMID- 8986476
TI  - A predictive model for the treatment approach to community-acquired pneumonia in
      patients needing ICU admission.
AB  - OBJECTIVE: To create a predictive model for the treatment approach to community
      acquired pneumonia (CAP) in patients needing Intensive Care Unit (ICU) admission.
      DESIGN: Multicenter prospective study. SETTING: Twenty-six Spanish ICUs.
      PATIENTS: One hundred seven patients with CAP, all of them with accurate
      etiological diagnosis, divided in three groups according to their etiology in
      typical (bacterial pneumonia), Legionella and other atypical (Mycoplasma,
      Chlamydia spp. and virus). For the multivariate analysis we grouped Legionella
      and other atypical etiologies in the same category. METHODS: We recorded 34
      variables including clinical characteristics, risk factors and radiographic
      pattern. We used a multivariate logistic regression analysis to find out a
      predictive model. RESULTS: We have the complete data in 70 patients. Four
      variables: APACHE II, (categorized as a dummy variable) serum sodium and
      phosphorus and "length of symptoms" gave an accurate predictive model (c =
      0.856). From the model we created a score that predicts typical pneumonia with a
      sensitivity of 90.2% and specificity 72.4%. CONCLUSION: Our model is an attempt
      to help in the treatment approach to CAP in ICU patients based on a predictive
      model of basic clinical and laboratory information. Further studies, including
      larger numbers of patients, should validate and investigate the utility of this
      model in different clinical settings.

PMID- 8986477
TI  - The intensive care management, mortality and prognostic indicators in severe
      community-acquired pneumococcal pneumonia.
AB  - OBJECTIVE: To determine mortality and factors that might predict outcome in
      severe community-acquired pneumococcal pneumonia treated by a standard protocol.
      DESIGN: Prospective, non-concurrent study. SETTING: Respiratory intensive care
      unit (ICU) in a teaching hospital. PATIENTS: 63 patients who were diagnosed by
      positive blood culture or Gram stain and culture of sputum or tracheal aspirate
      were included. MEASUREMENTS AND RESULTS: Clinical features, severity scores
      including Acute Physiology and Chronic Health Evaluation (APACHE) II, organ
      failure and lung injury scores, and the clinical course in the ICU were
      documented; 79% of patients required mechanical ventilation. Bacteraemia was
      present in 34 patients (54%); there were no distinguishing clinical features
      between bacteraemic and non-bacteraemic cases. The overall mortality was 21%,
      with only 5 deaths (15% mortality) in the bacteraemic group. Shock and a very low
      serum albumin (< 26 g/l) were the only clinical features that differentiated
      survivors from non-survivors; lung injury, APACHE II and multiple organ failure
      scores were all predictive of outcome. The positive predictive value and
      specificity in predicting death in individuals for the modified British Thoracic
      Society rule 1 were 26 and 64%; APACHE II > 2057 and 88%; > 2 organ failure 64
      and 92%; and lung injury > 233 and 73%, respectively. CONCLUSIONS: These results
      suggest that even in bacteraemic cases mortality should be below 25% with
      intensive care management and that conventional scoring systems, while predictive
      of group mortality, are unreliable in individuals.

PMID- 8986478
TI  - Severe community-acquired pneumonia in ICUs: prospective validation of a
      prognostic score.
AB  - OBJECTIVE: To determine predictors of intensive care unit (ICU) mortality in
      patients with community-acquired pneumonia (CAP), to develop a pneumonia-specific
      prognostic index, and to evaluate this index prospectively. DESIGN: Combined
      retrospective and prospective clinical study over two periods: January 1987
      December 1992 and January 1993-December 1994. SETTING: Four medical ICUs in the
      north of France. PATIENTS: Derivation cohort: 335 patients admitted to one ICU
      were retrospectively studied to determine prognosis factors and to develop a
      pneumonia-specific prognostic index. Validation cohort: 125 consecutive patients,
      admitted to four ICUs, were prospectively enrolled to evaluate this index.
      RESULTS: In the derivation cohort, 16 predictors of mortality were identified and
      assigned a value directly proportional to their magnitude in the mortality model:
      aspiration pneumonia (-0.37), grading of sepsis > or = 11 (-0.2), antimicrobial
      combination (-0.01), Glasgow score > 12+mechanical ventilation (MV) (+0.09),
      serum creatinine > or = 15 mg/l (+0.22), chest involvement shown by X-ray > or =
      3 lobes (+0.28), shock (+0.29), bacteremia (+0.29), initial MV (+0.29),
      underlying ultimately or rapidly fatal illness (+0.31), Simplified Acute
      Physiology Score > or = 12 (+0.49), neutrophil count < or = 3500/ mm3 (+0.52),
      acute organ system failure score > or = 2 (+0.64), delayed MV (+0.67),
      immunosuppression (+1.38), and ineffective initial antimicrobial therapy (+1.5).
      An index was obtained by adding each patient's points. According to a receiver
      operating characteristic curve, the cut-off value of this index was 2.5. In the
      validation cohort, an index of > or = 2.5 could predict death with a positive
      predictive value of 0.92, sensitivity 0.61, and specificity 0.98. CONCLUSION:
      This index, which performs well in classifying patients at high-risk of death,
      may help physicians in initial patient care (appropriateness of the initial
      antimicrobial therapy) and guide future clinical research (analysis and design of
      therapeutic trials).

PMID- 8986479
TI  - Outcome of ICU treatment in invasive aspergillosis.
AB  - OBJECTIVE: To assess the outcome of intensive care treatment in invasive
      aspergillosis. DESIGN: Retrospective study. SETTING: University Hospital, Medical
      Intensive Care Unit (ICU). PATIENTS: Twenty-five patients with invasive
      aspergillosis who were admitted to the medical ICU in a 5 1/2 year period. Twenty
      two had received high-dose chemotherapy for (mainly hematologic) malignancies,
      one had been treated with cyclosporine and prednisolone for systemic lupus
      erythematosus, one with high-dose methylprednisolone for polyarteritis nodosa and
      one had an ARDS after near-drowning. MEASUREMENTS AND RESULTS: The medical
      records were reviewed for patient and disease characteristics, outcome, reasons
      for admission to the ICU, supportive care and antifungal therapy as well as for
      the results of cultures and autopsy. Out of 25 patients, a definite ante mortem
      diagnosis could be established in seven. When autopsied patients were included, a
      total of 15 suffered from proven invasive aspergillosis. Although standard
      antifungal treatment and maximal available supportive care were given, 23 of 25
      patients (92%) died after a mean of 15 (1-51) days in the ICU. Both patients who
      recovered had received high-dose chemotherapy for hematologic malignancy and
      showed bone marrow recovery and/or had a localized pulmonary infection.
      CONCLUSIONS: In patients with highly suspected or proven invasive aspergillosis,
      admission to an ICU and mechanical ventilation should be considered in cases of
      localized infection and obvious signs of hematologic recovery. In most other
      circumstances ICU admission for mechanical ventilation does not seem to improve
      survival.

PMID- 8986480
TI  - Treatment of respiratory failure using minitracheotomy and intratracheal
      oxygenation in selected patients with chronic lung disease.
AB  - OBJECTIVE: To evaluate the efficacy of minitracheotomy (MT) insertion for
      intratracheal oxygen insufflation (ITO2) on arterial blood gases and survival in
      patients with respiratory failure from chronic lung disease. DESIGN: Open,
      prospective clinical study. SETTING: A 12-bed medical intensive care unit in a
      non-university hospital. PATIENTS: 20 patients (14 males and 6 females, mean age
      74.8 +/- 2.6 years), admitted for respiratory failure and denied mechanical
      ventilation. INTERVENTION: Percutaneous insertion of an MT for ITO2. Arterial
      blood gases were drawn just prior to, then 3, 24, 48 h and 1 week after MT
      insertion. Data are evaluated with a two-way analysis of variance for
      distribution-free data (Friedman's rank sums test). MEASUREMENTS AND RESULTS:
      Three hours after starting ITO2, the partial pressure of oxygen in arterial blood
      (PaO2) and the arterial oxygen saturation (SaO2) both increased from 51.7 +/- 2.8
      to 85.4 +/- 5.6 mmHg and from 79.7 +/- 3.1 to 93.7 +/- 0.9%, respectively (p <
      0.001 for both), along with a slight worsening in the partial pressure of carbon
      dioxide in arterial blood (PaCO2), from 59.6 +/- 2.5 to 63.5 +/- 3.0 mmHg (p <
      0.05). At 1 week, improvements in PaO2 and SaO2 were maintained in all patients,
      while PaCO2 decreased in 14 patients (mean decrease 8.3 mmHg) and increased in
      the remaining patients (mean 12.5 mmHg), when compared to pre-ITO2 values. Seven
      patients died during follow-up, leading to a success rate of 65%. Eight and 4
      patients were discharged home and to a nursing home, respectively, 9 still
      receiving ITO2 via MT as chronic oxygen therapy. CONCLUSION: Our results suggest
      that MT insertion for ITO2 may be a therapeutic option in selected patients with
      respiratory failure from CLD.

PMID- 8986481
TI  - New aspects of pulmonary mechanics: "slowly" distensible compartments of the
      respiratory system, identified by a PEEP step maneuver.
AB  - OBJECTIVE: The aims of the present study were 1) to evaluate a method for
      identification of "slowly" distensible compartments of the respiratory system
      (rs), which are characterized by long mechanical time constants (RC) and 2) to
      identify "slowly" distensible rs-compartments in mechanically ventilated
      patients. DESIGN: Prospective study on a physical lung model. SETTING: Intensive
      Care Unit, University Hospital, Tubingen. PATIENTS AND PARTICIPANTS: 19 patients
      with severe lung injury (acute respiratory distress syndrome, ARDS) and on 10
      patients with mild lung injury. MEASUREMENTS AND RESULTS: Positive end-expiratory
      pressure (PEEP)-increasing and -decreasing steps of about 5 cmH2O were applied
      and the breath-by-breath differences of inspiratory and expiratory volumes (delta
      V) were measured. The sequence of delta Vs were analyzed in terms of volume
      change in the "fast" compartment (Vfast), the "slow" compartment (Vslow), total
      change in lung volume (delta VL) and mechanical time constant of the slow
      compartment (RCslow). Thirty-eight measurements in a lung model revealed a good
      correlation between the preset Vslow/delta VL and Vslow/delta VL measured: r2 =
      0.91. The Vslow/delta VL measured amounted to 0.94 +/- 0.15 of Vslow/delta VL in
      the lung model. RCslow measured was 0.92 +/- 0.43 of the RCslow reference.
      Starting from a PEEP level of 11 cmH2O PEEP-increasing and PEEP-decreasing steps
      were applied to the mechanically ventilated patients. Three out of ten patients
      with mild lung injury (30%) and 7/19 patients with ARDS (36.8%) revealed "slowly"
      distensible rs-compartments in a PEEP-increasing step, whereas 15/19 ARDS
      patients and 1/10 patients with mild lung injury showed "slowly" distensible rs
      compartments in a PEEP-decreasing step (78.9% vs 10%, P < 0.002, chi-square
      test). CONCLUSIONS: The gas distribution properties of the respiratory system can
      be easily studied by a PEEP-step maneuver. The relative contribution of the
      "slow" units to the total increase of lung volume following a PEEP step could be
      adequately assessed. "Slowly" distensible rs-compartments could be detected in
      patients with severe and mild lung injury, however significantly more ARDS
      patients revealed "slow" rs-compartments in PEEP-decreasing steps. The influence
      of "slowly" distensible rs-compartments on pulmonary gas exchange is unknown and
      has yet to be studied.

PMID- 8986482
TI  - Routine daily chest radiography is not indicated for ventilated patients in a
      surgical ICU.
AB  - OBJECTIVE: To determine a) if clinical examination can accurately predict
      radiological change and b) if routine chest radiography is efficacious. DESIGN:
      All mechanically ventilated patients admitted to the Surgical Intensive Care Unit
      over a 4-week period were enrolled into the study. A physical examination was
      undertaken by two clinicians to predict significant (radiographic features which
      alter management) and insignificant (radiographic features which do not alter
      management) changes. The radiographs were then reviewed by a radiologist who
      noted any changes from previous radiographs. The clinical findings were then
      correlated with the radiographical findings. SETTING: The study was conducted in
      a 16-bedded Surgical Intensive Care Unit which admits approximately 800 patients
      per year. The majority of these patients require mechanical ventilation. PATIENTS
      AND PARTICIPANTS: All patients who required mechanical ventilation were included.
      Thirty-four patients were studied. The patients were young adults admitted
      primarily following trauma with a low incidence of pre-existing disease.
      INTERVENTIONS: There were no interventions in this study. MEASUREMENTS AND
      RESULTS: One hundred sixty-four radiographs were evaluated. Both examiners were
      efficient in predicting significant changes (sensitivity of 93 and 97%), but less
      efficient at predicting insignificant changes (sensitivity of 74 and 70%). Two
      significant radiographical changes were missed on clinical examination: one
      catheter malposition and one pneumothorax, representing a yield from radiography
      of 1%. A 52% reduction in the number of radiographs would have resulted if the
      need for radiography had been determined by clinical examination. CONCLUSIONS:
      Clinical examination can effectively predict the need for radiography. Routine
      chest radiography is, therefore, not indicated for ventilated patients in our
      Surgical Intensive Care Unit.

PMID- 8986483
TI  - Impaired gastric emptying in mechanically ventilated, critically ill patients.
AB  - OBJECTIVE: To measure gastric emptying in critically ill patients using an
      acetaminophen absorption model and determine which variables are associated with
      impaired gastric emptying. DESIGN: A prospective, cohort study. SETTING: A
      medical/surgical ICU at a tertiary care hospital: Hamilton General Hospital,
      Hamilton, Ontario. PATIENTS AND PARTICIPANTS: We recruited 72 mechanically
      ventilated patients expected to remain in the ICU for more than 48 h. Our results
      were compared to those in healthy volunteers. INTERVENTION: Within 48 h of
      admission to the ICU, 1.6 g acetaminophen suspension were administered via a
      nasogastric tube into the stomach. Blood samples were drawn a t = 0, 30, 60, 90,
      and 120 min for measurement of plasma acetaminophen levels determined by the
      enzymatic degradation method. MEASUREMENTS AND RESULTS: Maximal concentration of
      acetaminophen was 94.1 (75.3) mumol/l compared to 208.4 (33.1) mumol/l in a
      control population (p < 0.0001). The time to reach the maximal concentration was
      105 min (60-180) compared to 30 min (15-90) in controls (p < 0.0001). The area
      under the time-acetaminophen concentration curve t = 120 was 9301 (7343)
      mumol/min per l compared to 11644 (1336) mumol/min per l in the controls (p =
      0.28). The variables associated with delayed gastric emptying were age, sex and
      use of opioids for analgesia and sedation. CONCLUSIONS: Gastric emptying is
      delayed in critically ill patients. The important consequences of this phenomenon
      include intolerance to enteral nutrition and gastric colonization. Strategies to
      minimize the use of narcotics may improve gastric emptying. Studies to examine
      the effect of gastrointestinal prokinetic agents on gastric emptying are needed.

PMID- 8986484
TI  - Effects of continuous (CPAP) and bi-level positive airway pressure (BiPAP) on
      extravascular lung water after extubation of the trachea in patients following
      coronary artery bypass grafting.
AB  - OBJECTIVE: To evaluate the effects of continuous positive airway pressure (CPAP)
      and bi-level positive airway pressure (Bi-PAP) on extravascular lung water during
      weaning from mechanical ventilation in patients following coronary artery bypass
      grafting. DESIGN: Prospective, randomized clinical study. SETTING: Intensive care
      unit at a university hospital. PATIENTS: Seventy-five patients following coronary
      artery bypass grafting. INTERVENTIONS: After extubation of the trachea, patients
      were treated for 30 min with CPAP via face mask (n = 25), with nasal BiPAP (n =
      25), or with oxygen administration via nasal cannula combined with routine chest
      physiotherapy (RCP) for 10 min (n = 25). MEASUREMENTS AND RESULTS: Extravascular
      lung water (EVLW), pulmonary blood volume index (PBVI) and cardiac index (CI)
      were obtained during mechanical ventilation (T1), T-piece breathing (T2),
      interventions (T3), spontaneous breathing 60 min (T4) and 90 min (T5) after
      extubation of the trachea using a combined dye-thermal dilution method. Changing
      from mechanical ventilation to T-piece breathing did not show any significant
      differences in EVLW between the three groups, but a significant increase in PBVI
      from 155 +/- 5 ml/m2 to 170 +/- 4 ml/m2 could be observed in all groups (p <
      0.05). After extubation of the trachea and treatment with BiPAP. PBVI decreased
      significantly to 134 +/- 6 ml/m2 (p < 0.05). After treatment with CPAP or BiPAP,
      EVLW did not change significantly in these groups (5.5 +/- 0.3 ml/kg vs 5.0 +/-
      0.4 ml/kg and 5.1 +/- 0.4 ml/kg vs 5.7 +/- 0.4 ml/kg). In the RCP-treated group,
      however, EVLW increased significantly from 5.8 +/- 0.3 ml/kg to 7.1 +/- 0.4 ml/kg
      (p < 0.05). Sixty and 90 min after extubation, EVLW stayed at a significantly
      higher level in the RCP-treated group (7.5 +/- 0.5 ml/kg and 7.4 +/- 0.5 ml/kg)
      than in the CPAP-(5.6 +/- 0.3 ml/kg and 5.9 +/- 0.4 ml/kg) or BiPAP-treated
      groups (5.2 +/- 0.4 ml/kg and 5.2 +/- 0.4 ml/kg). No significant differences in
      CI could be observed within the three groups during the time period from
      mechanical ventilation to 90 min after extubation of the trachea. CONCLUSIONS:
      Mask CPAP and nasal BiPAP after extubation of the trachea prevent the increase in
      extravascular lung water during weaning from mechanical ventilation. This effect
      is seen for at least 1 h after the discontinuation of CPAP or BiPAP treatment.
      Further studies have to evaluate the clinical relevance of this phenomenon.

PMID- 8986485
TI  - Intrapleural administration of streptokinase in complicated purulent pleural
      effusion: a CT-guided strategy.
AB  - OBJECTIVE: To determine the usefulness and the results of a strategy using
      intrapleural streptokinase (SK) instillation guided by repeated computed
      tomography (CT) scan examinations in pleural empyemas unresponsive to chest tube
      drainage. DESIGN: A retrospective chart review. SETTING: The medical Intensive
      Care Unit and Department of Radiology, in a university hospital. PATIENTS:
      Sixteen patients with empyema who had a persistent pleural effusion despite
      drainage, among 37 patients with infectious pleural effusion. INTERVENTIONS: In
      the 16 patients, CT examination was performed before and at least once after SK.
      Intrapleural SK was instilled, either through the chest tube or via a needle
      puncture, according to the CT scan results. RESULTS: The first CT scan confirmed
      a persistent effusion in all, showing a multiloculated effusion in 13 patients,
      and an ectopic loculus in one. The first SK instillation resulted in a dramatic
      increase of fluid drained per day (from 68 +/- 28 ml to 567 +/- 262 ml; p <
      0.001), leading to complete resolution in 11 patients, while the others required
      a second CT scan-guided procedure. In one, the chest tube was misplaced, while in
      two, transparietal injection was needed. Finally, a complete resolution was
      observed in 14 (87.5%) of the patients. Two patients had a poor initial response
      to SK and were eventually scheduled for video-thoracoscopy. A single episode of
      chills and fever was observed among 32 SK instillations. CONCLUSION: CT-guided SK
      instillation in pleural empyema appears to be safe, and allowed complete
      resolution in 87.5% of our patients.

PMID- 8986486
TI  - Splanchnic blood flow is greater in septic shock treated with norepinephrine than
      in severe sepsis.
AB  - OBJECTIVE: To assess global and splanchnic blood flow and oxygen transport in
      patients with sepsis with and without norepinephrine treatment. DESIGN:
      Prospective, clinical study. SETTING: University hospital intensive care unit.
      PATIENTS: A convenience sample of 15 septic shock patients treated with
      norepinephrine and 13 patients with severe sepsis who did not receive
      norepinephrine. MEASUREMENTS AND MAIN RESULTS: There were no differences between
      the two groups in global haemodynamics and oxygen transport. Splanchnic blood
      flow and oxygen delivery (splanchnic DO2 303 +/- 43 ml/min per m2) and
      consumption (splanchnic VO2 100 +/- 13 ml/min per m2) were much higher in the
      septic shock group compared with the severe sepsis group (splanchnic DO2 175 +/-
      19 ml/min per m2, splanchnic VO2 61 +/- 6 ml/min per m2). Gastric mucosal pH was
      subnormal in both groups (septic shock 7.29 +/- 0.02, severe sepsis 7.25 +/-
      0.02) with no significant difference. No significant differences between groups
      were detected in lactate values. CONCLUSION: These data confirm a redistribution
      of blood flow to the splanchnic region in sepsis that is even more pronounced in
      patients with septic shock requiring norepinephrine. However, subnormal gastric
      mucosal pH suggested inadequate oxygenation in parts of the splanchnic region due
      to factors other than splanchnic hypoperfusion. Progress in this area will depend
      on techniques that address not only total splanchnic blood flow, but also inter
      organ flow distribution, intra-organ distribution, and other microcirculatory or
      metabolic malfunctions.

PMID- 8986487
TI  - Effect of hemofiltration on hemodynamics and systemic concentrations of
      anaphylatoxins and cytokines in human sepsis.
AB  - OBJECTIVE: To determine whether hemofiltration (HF) can eliminate cytokines and
      complement components and alter systemic hemodynamics in patients with severe
      sepsis. DESIGN: Prospective observation study. SETTING: Surgical intensive care
      unit of a university hospital. PATIENTS: 16 patients with severe sepsis.
      INTERVENTIONS: Continuous zero-balanced HF without dialysis (ultrafiltrate rate 2
      l/h) was performed in addition to pulmonary artery catheterization, arterial
      cannulation, and standard intensive care treatment. MEASUREMENTS AND MAIN
      RESULTS: Plasma and ultrafiltrate concentrations of cytokines (the interleukins
      IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha) and of complement
      components (C3adesArg, C5adesArg) were measured after starting HF (t0) and 4 h
      (t4) and 12 h later (t12). Hemodynamic variables including mean arterial pressure
      (MAP), mean central venous pressure, mean pulmonary artery pressure, pulmonary
      capillary wedge pressure, and cardiac output were serially determined. During HF,
      cytokine plasma concentrations remained constant. However, C3adesArg and
      C5adesArg plasma concentrations showed a significant decline during 12-h HF
      (C3adesArg: t0 = 676.9 +/- 99.7 ng/ml vs t12 = 467.8 +/- 71, p < 0.01; C5adesArg:
      26.6 +/- 4.7 ng/ml vs 17.6 +/- 6.2, p < 0.01). HF resulted in a significant
      increase over time in systemic vascular resistance (SVR) and MAP (SVR at t0: 669
      +/- 85 dyne.s/cm5 vs SVR at t12: 864 +/- 75, p < 0.01; MAP at t0: 69.9 +/- 3.5
      mmHg vs MAP at t12: 82.2 +/- 3.7, p < 0.01). CONCLUSIONS: HF effectively
      eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis. There was
      also a significant rise in SVR and MAP during high volume HF. Therefore, HF may
      represent a new modality for removal of anaphylatoxins and may, thereby, deserve
      clinical testing in patients with severe sepsis.

PMID- 8986488
TI  - The performance of SAPS II in a cohort of patients admitted to 99 Italian ICUs:
      results from GiViTI. Gruppo Italiano per la Valutazione degli interventi in
      Terapia Intensiva.
AB  - OBJECTIVE: To assess the validity of SAPS II (new Simplified Acute Physiology
      Score) in a cohort of patients admitted to a large sample of Italian intensive
      care units (ICU). DESIGN AND SETTING: The ability of the SAPS II scoring system
      to predict the probability of hospital mortality was assessed with calibration
      and discrimination measures obtained using published coefficients. A new logistic
      regression equation was then developed and further formal calibration and
      discrimination measures were estimated for the customized model. PATIENTS: From
      the 2202 consecutive patients recruited during a 1-month period in 99 ICUs, a
      total of 1393 patients were included in this validation study. RESULTS: When the
      parameters based on the standard model were applied, the expected probability of
      mortality did not fit those actually observed in the cohort (p < 0.001), although
      it showed satisfactory discrimination (area under the receiver operating
      characteristic curve = 0.80). Such lack of fit yields an overall under prediction
      of mortality (observed/expected ratio = 1.14) that reflects a uniform pattern
      across a preselected set of subgroups. Customization allowed new mortality
      estimates to be calculated, with satisfactory calibration (p = 0.82) and a more
      uniform pattern across subgroups. CONCLUSIONS: SAPS II maintained its validity in
      an independent sample of patients recruited in a large network of Italian ICUs
      only after appropriate adaptation (first-level customization). Whether the
      determinants of this relatively poor performance are related to differences in
      unmeasured case-mix, methods of application, or quality of care delivered is a
      matter for discussion that cannot be solved with the data presently available.
      However, these findings suggest that caution is warranted before implementing the
      standard SAPS II scoring system parameters outside formal research projects.

PMID- 8986489
TI  - Measuring health and health state preferences among critically ill patients.
AB  - OBJECTIVE: a) to examine the EuroQol instrument's ability to assess a patient's
      state of health prior to admission to an ICU; b) to describe a patient's health
      related quality of life (HRQoL) before the onset of the condition leading to
      admission to the ICU, and prior to discharge; c) to compare patients' preferences
      for a "common core" of EuroQol health states with preferences from healthy
      individuals. DESIGN: Patients in a step-down unit (SDU) retrospectively rated
      their health states prior to admission to the ICU, their current states of health
      and the "common core" of hypothetical EuroQol states of health. Proxies rated the
      patients' health states prior to admission to the ICU. Patients' preferences for
      EuroQol states of health were compared with the preferences obtained from a
      retrospective cohort of healthy individuals. SETTING: An SDU at the University
      Hospital of Bellvitge, Barcelona, Spain. PATIENTS: 103 critical medical and
      surgical patients were interviewed. INTERVENTION: The EuroQol questionnaire, a
      non-disease specific instrument to evaluate HRQoL. MEASUREMENTS AND MAIN RESULTS:
      Agreement between patients and proxies regarding their prior health state was
      moderate to good in physical and pain areas (kappa: 0.43-0.58), fair for mood
      (kappa: 0.38) and almost identical for prior overall health (65.9 vs 66.3).
      Compared with their prior HRQoL, patients had deteriorated in all physical areas
      and overall health at discharge from the SDU. Preferences for the worst health
      states varied significantly between patients and healthy individuals. CONCLUSION:
      The EuroQol can be reliably used with proxies to determine the state of health of
      patients prior to admission to the ICU. Preferences between healthy individuals
      and ICU patients differed.

PMID- 8986491
TI  - Severe head injuries: an outcome prediction and survival analysis.
AB  - OBJECTIVE: To identify the predictors determined early after admission and
      associated with unfavorable outcome or early (within 48 h) death after severe
      head injury. DESIGN: Prospective cohort study. SETTING: A neurosurgical intensive
      care unit in a university hospital. PATIENTS: 198 consecutive comatose patients
      hospitalized from 1989 to 1992. RESULTS: Logistic regression showed that a
      combination of age, best motor response score from the Glasgow Coma Scale, and
      hypoxia provided a good prediction model of unfavorable outcome (sensitivity =
      0.93). The length of participation of survivors was 6 to 61 months (median 27.1).
      The Cox model demonstrated age, motor score less than 3, mydriasis, and hypoxia
      as poor prognosis factors. CONCLUSIONS: Clinicians can determine the odds of a
      good outcome from the combination of three easily measurable factors using a
      simple diagram constructed from logistic regression. Survival analysis showed
      that motor score adjusted values greater than 3 had the same prognosis.

PMID- 8986490
TI  - Assessment of depth of midazolam sedation using objective parameters.
AB  - OBJECTIVE: To determine the relationship between the clinically evaluated depth
      of midazolam-induced sedation and the cardiac beat-to-beat variability (RR
      variability) in ICU patients in the intensive care unit (ICU). DESIGN:
      Prospective study. SETTING: ICU of a university hospital. PATIENTS: 20
      consecutive patients studied during weaning from mechanical ventilation and
      withdrawal of midazolam-induced sedation. MEASUREMENTS AND RESULTS: After
      clinical evaluation of depth of sedation according to the Ramsay sedation score,
      the RR variability over 512 RR intervals and predominant respiratory rate were
      measured. The power spectrum of RR variability was calculated by a fast Fourier
      transformation and the resulting total frequency band (0.016-0.35 Hz) was
      subdivided into a very low, a low, and a high frequency band. Stepwise multiple
      regression analysis in the first 10 patients (group 1) showed a significant
      relationship between depth of sedation and measures of RR variability combined
      with respiratory rate (r2 = 0.59; F = 12.1; p < 0.001). The more effective
      sedation was, the more depressed were both RR variability and predominant
      respiratory rate. Mean heart rate, mean respiratory rate, median deviation of RR
      intervals from the mean, and the ratio between spectral power density in the high
      and the low frequency bands proved to be the most important predictors of the
      Ramsay score (+/-1 level accuracy: 87%, p < 0.001). Using this regression
      equation, the Ramsay score was predicted in the remaining 10 patients (group 2)
      with a +/-1 level of accuracy of 81% (p < 0.001). CONCLUSION: In ICU patients, a
      significant correlation is found between the depth of midazolam-induced sedation
      as assessed by the Ramsay sedation score and RR variability, with a clinically
      sufficient prediction accuracy. RR variability can serve as an objective,
      continuously available, and non-invasive measurement to monitor midazolam-induced
      sedation in intubated and mechanically ventilated patients.

PMID- 8986492
TI  - Changes in cardiac output during air ambulance repatriation.
AB  - OBJECTIVES: To measure, with the use of suprasternal Doppler ultrasound, the
      hemodynamic changes in patients and volunteers during air ambulance repatriation.
      DESIGN: Unblinded prospective observational study. SETTING: Chartered air
      ambulances for the international repatriation of patients. PATIENTS AND
      PARTICIPANTS: Six medical crew members and seven patients transported back to
      hospitals in the UK. INTERVENTIONS: The measurement of non-invasive blood
      pressure, ECG, heart rate, oxygen saturation and hemodynamic variables with
      suprasternal Doppler. MEASUREMENTS AND RESULTS: There was a drop in systolic and
      mean arterial blood pressure in the patient's group once in the air. Oxygen
      saturation dropped in both groups once at cruising altitude. Heart rate remained
      unchanged. Stroke distance and minute distance increased significantly in the
      patient's group and non-significantly in the volunteers. Peak velocity increased
      significantly in the patient's group. There was an overall reduction of systemic
      vascular resistance during take off and once at cruising altitude. CONCLUSIONS:
      Hemodynamic changes happen during air ambulance transportation in fit and healthy
      volunteers and patients alike. These may be due to a combination of hypobaric
      hypoxia and gravitational forces. It is necessary to establish if these changes
      have short- or long-term effects in the critically ill.

PMID- 8986493
TI  - Therapeutic trial of diazepam versus placebo in acute chloroquine intoxications
      of moderate gravity.
AB  - OBJECTIVE: Acute chloroquine intoxication is responsible for a membrane
      stabilising effect which results in electrocardiographic (ECG) and hemodynamic
      disturbances. Diazepam is used in acute chloroquine intoxication on the basis of
      clinical and experimental observations, but its utility alone, in man, remains
      unproven. The goal of this study was to verify whether diazepam alone has an
      effect on the membrane-stabilising effect observed in moderately severe
      chloroquine intoxications. DESIGN: Prospective, multi-center, double-blind,
      placebo-controlled study. SETTING: Prehospital mobile intensive care units
      (Paris) and hospital intensive care units (paris and Dakar). PATIENTS AND
      PARTICIPANTS: Adults with moderately severe intoxication defined as: a suspected
      ingested dose of 2 or more but less than 4 g, systolic blood pressure (SBP)
      higher than 80 mmHg, QRS duration less than 0.12 s and the absence of dysrhythmia
      at inclusion. INTERVENTIONS: Patients received either a loading dose of 0.5 mg/kg
      diazepam followed by an infusion of 1 mg/kg over 24 h or an equivalent volume of
      placebo. MEASUREMENTS AND RESULTS: Outcome was measured by serial assessments of
      SBP, ECG (QRS and QT segments) and clinical deterioration. There were no
      significant differences observed in the initial or serial ECG or SBP
      measurements. There were no deaths and no patient had to be removed from the
      study due to clinical deterioration. CONCLUSIONS: Diazepam, at the dose studied,
      does not appear to reverse the chloroquine-induced membrane-stabilising effect in
      acute moderately severe chloroquine intoxication. Supportive intensive care of
      these intoxications appears to be all that is necessary.

PMID- 8986494
TI  - Long-term management of acute respiratory failure in metabolic myopathy.
AB  - OBJECTIVE: To describe how patients cope with the proposal of treatment with
      intermittent artificial ventilation after acute respiratory failure due to
      progressive respiratory muscle weakness. DESIGN: Case series, follow-up study.
      SETTING: Neurological intensive care unit (ICU). PATIENTS: 7 consecutive patients
      with metabolic myopathy treated for acute respiratory failure between 1983 and
      1992. INTERVENTIONS: Intermittent positive pressure ventilation (IPPV) via
      tracheostomy. MEASUREMENTS AND RESULTS: Symptoms of chronic hypoventilation
      preceded acute respiratory failure for months. With one exception, patients were
      mainly disabled from respiratory muscle weakness and sleep-related breathing
      disorders. IPPV was recommended to prevent recurrent respiratory failure. Two of
      three patients who accepted home IPPV returned to full-time jobs. One patient,
      who decided against IPPV, died from CO2 narcosis several months after discharge.
      All patients adhered to the respiratory regimen once instituted. CONCLUSIONS:
      Acute respiratory failure in chronic myopathy is heralded by daytime drowsiness.
      IPPV, or at least regular monitoring of waking and sleeping partial pressure of
      carbon dioxide, is highly recommended even if weaning is successful. IPPV
      improved quality of life. The treatment strategy at discharge from the ICU should
      be optimal, as patients are reluctant to modify regimens.

PMID- 8986495
TI  - Atrial septostomy under transesophageal guidance in a patient with primary
      pulmonary hypertension and absent right superior vena cava.
AB  - A patient presenting primary pulmonary hypertension and absent right superior
      vena cava underwent blade/balloon atrial septostomy as palliative therapy. Due to
      the anomaly of the venous drainage system, only transesophageal echocardiography
      allowed the performance of the maneuvre.

PMID- 8986496
TI  - Lung lavage with a saline volume similar to functional residual capacity followed
      by surfactant administration in newborns with severe meconium aspiration
      syndrome.

PMID- 8986497
TI  - Continuous arterial gas monitoring: initial experience with the Paratrend 7 in
      children.
AB  - OBJECTIVE: To describe clinical usage of the Paratrend 7 continuous arterial
      blood gas monitor in children. DESIGN: Children older than 24 months of age who
      required significant ventilatory intervention were eligible for sensor placement.
      INTERVENTIONS: The sensor was placed via the arterial catheter to measure pH,
      PCO2, PO2, and temperature. The simultaneous arterial blood gas value was
      recorded along with the sensor reading. RESULTS: The sensor functioned for as
      long as seven days and provided the clinicians with data on the patient's
      respiratory status. The statistical validity of the device when compared to the
      arterial blood gas showed that the bias/precision for pH was 0.006/0.024, for
      PCO2 -0.78/4.68 mmHg, and for PO2 1.9%/17.1% (mmHg). CONCLUSIONS: This report
      demonstrates actual clinical use of continuous blood gas monitoring in children.
      The information obtained is a major asset to the management of critically ill
      children in the intensive care unit.

PMID- 8986498
TI  - Initial postoperative serum lactate levels predict survival in children after
      open heart surgery.
AB  - OBJECTIVE: To evaluate the relationship between postoperative serum lactate
      levels and outcome in children undergoing open heart surgery. DESIGN:
      Prospective, noninterventional study. SETTING: Pediatric intensive care unit
      (PICU) of a university hospital. PATIENTS: 41 nonconsecutive children who had had
      cardiopulmonary bypass for repair of congenital heart disease. INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: Serum lactate levels were measured on admission
      to the PICU immediately after open heart surgery. Lactate levels were correlated
      with bypass and cross clamp times, estimated intraoperative blood loss, lowest
      temperature on bypass, admission Pediatric Risk of Mortality score, anion gap,
      and measures of postoperative morbidity. Mean lactate levels on admission to the
      PICU were 6.86 +/- 0.79 mmol/l for nonsurvivors (n = 7) and 2.38 +/- 0.13 mmol/l
      for survivors (n = 34) (p < 0.0001), and 4.87 +/- 0.7 mmol/l and 2.35 +/- 0.19
      mmol/l, for patients with (n = 11) and without (n = 30) multiple organ system
      failure, respectively (p < 0.0001). Admission lactate levels correlated with all
      measurements of postoperative morbidity. A serum lactate level of greater than
      4.2 mmol/l had a positive predictive value of 100% and a negative predictive
      value of 97% for postoperative death. CONCLUSIONS: Initial postoperative serum
      lactate levels after pediatric open heart surgery may be predictive of outcome.
      Lactate levels are also higher in patients who go on to develop multiple organ
      system failure. Elevated postoperative lactate levels may reflect intraoperative
      tissue hypoperfusion, and measures aimed at increasing oxygen delivery, with
      normalization of lactate, may improve patient outcome.

PMID- 8986499
TI  - Intensive care management of paediatric organ donors and its effect on post
      transplant organ function.
AB  - OBJECTIVES: 1. To document the clinical course of paediatric beating heart organ
      donors. 2. To evaluate the effect of the ICU management of pediatric donors on
      the immediate function of transplanted organs. 3. To examine the validity of
      current donor selection criteria. DESIGN: Retrospective chart review and case
      series study. SETTING: Multidisciplinary ICU of tertiary referral paediatric
      hospital. PATIENTS: All patients who became solid organ donors between January
      1980 and July 1990. OUTCOME MEASURES: 1. Incidence of major physiological
      abnormalities of the cardiovascular, pulmonary, renal and metabolic systems. 2.
      Number of organs retrieved and transplanted, reasons for non-transplantation of
      donated organs. 3. Immediate post-transplant function of transplanted organs.
      RESULTS: Seventy-seven organ donors were identified from whom 134 kidneys, 31
      livers and 12 hearts were transplanted. Sixty (78%) patients developed diabetes
      insipidus. Sustained hypotension occurred in 41 (53.2%) and was commoner in
      patients treated with inotropic agents in the presence of a low central venous
      pressure and in patients with diabetes insipidus who did not receive anti
      diuretic hormone replacement. Twenty-seven patients suffered at least one cardiac
      arrest. The data on post-transplant function were obtained for 129 kidneys (from
      70 donors) 30 livers and 9 hearts. Fifty-two kidneys, 10 livers and 2 hearts were
      transplanted from donors who had suffered at least one cardiac arrest without
      apparent adverse effect on post-transplant organ function. Thirty-six kidneys
      from 31 donors suffered either acute tubular necrosis (ATN) or primary non
      function. The donors of these organs spent longer in ICU (60.6 +/- 45.7 h versus
      41.8 +/- 30.1 h p = 0.045) and had a higher mean maximum serum sodium
      concentration (163.4 +/- 10.9 versus 158.5 +/- 9.5 mmol/l p = 0.05) than those
      without these complications. The serum creatinine concentration and degree of
      inotropic support did not predict post-transplant function. Standard biochemical
      tests for hepatic function, the dose of inotropic agent received, time in ICU and
      incidence of hypotension did not predict post-transplant liver function.
      CONCLUSIONS: Aggressive fluid resuscitation and management of diabetes insipidus
      may promote stability in paediatric organ donors. Donor cardiac arrest does not
      alter the ICU course or compromise post-transplant organ function. The current
      criteria used for donor selection failed to predict post-transplant organ
      function and their use may increase organ wastage.

PMID- 8986500
TI  - Meningococcal disease: a comparison of eight severity scores in 125 children.
AB  - OBJECTIVE: To investigate the accuracy of eight different prognostic scores
      (Stiehm, Niklasson, Leclerc, Garlund, the MOC score, Tesero, the Glasgow
      Meningococcal Septicaemia Prognostic Score (GMSPS) and Tuyzus) in the prediction
      of fatal outcome in meningococcal disease. DESIGN: Combined prospective and
      retrospective study. SETTING: A 175-bed pediatric department of a university
      hospital providing secondary care to +/- 180,000 inhabitants and serving as a
      referral center. The Pediatric Intensive Care (14 beds) is one of the six PICUs
      in the Netherlands and provides tertiary care for children under 18 years.
      PATIENTS: During an 8-year period (1986-1994) 125 children (mean age 4 years, 10
      months) with culture-proven meningococcal disease were studied: 34 patients
      presenting with meningitis, 33 patients with septic shock and 58 patients with
      meningitis and septic shock. MAIN RESULTS: All eight scores discriminated above
      average between survivors and non-survivors, as expressed by the corresponding
      Receiver Operator Characteristic (ROC) curves. The area under the ROC curve (AUC)
      ranged from 0.74 for the Garlund score to 0.93 for the GMSPS. The GMSPS performed
      significantly better than its competitors, even after exclusion of the base
      deficit as one of the score components (AUC = 0.92). It showed above average
      calibration when logistically transformed into a probability of mortality, and
      accurately identified a subgroup of patients with no mortality. None of the
      scores correctly identified non-survivors. CONCLUSION: The GMSPS is a simple
      score that can be reliably used for risk classification and the identification of
      low-risk patients.

PMID- 8986501
TI  - Gitaloxin poisoning in a child.
AB  - Gitaloxin is a digitalis glycoside used for the same indications as digoxin and
      digitoxin. The successful outcome for a 2 1/2-year-old boy who accidentally
      ingested 3 mg of gitaloxin (100 times the normal therapeutic dose) is reported.
      At admission the child presented with irregular heart rhythm. He subsequently
      started vomiting, even after continuous gastric feeding. Only 48 h after
      ingestion of gitaloxin he became somnolent and developed bradyarrhythmia. The
      symptoms disappeared 96 h later; the bradyarrhythmia, however, (second-degree
      atrioventricular block) decreased progressively only after 120 h. The initial
      clinical presentation of gitaloxin poisoning may be misleading and careful
      observation in a pediatric intensive care unit is mandatory. A cross-reaction
      between the fluorescence polarization immunoassay for digitoxin and the
      radioimmunoassay for gitaloxin was found and was used as a helpful, but rough,
      estimate of the severity of gitaloxin poisoning, in the absence of a specific
      measurement of gitaloxin.

PMID- 8986502
TI  - Pressure-limited ventilation with permissive hypercapnia and minimum PEEP in
      saline-lavaged rabbits allows progressive improvement in oxygenation, but does
      not avoid ventilator-induced lung injury.
AB  - OBJECTIVE: To determine whether pressure-limited intermittent mandatory
      ventilation with permissive hypercapnia and positive end-expiratory pressure
      (PEEP) titrated to arterial oxygen tension (PaO2) prevents or reduces acute lung
      injury, compared to conventional ventilation, in saline-lavaged rabbits. DESIGN:
      Prospective randomised trial. SETTING: University animal laboratory. SUBJECTS: 18
      New Zealand White rabbits. INTERVENTIONS: Following five sequential saline lung
      lavages, anaesthetised rabbits were randomly allocated in pairs to receive either
      of two ventilation protocols using intermittent mandatory ventilation. The study
      group had peak inspiratory pressure limited to 15 cm H2O and arterial partial
      pressure of carbon dioxide (PaCO2) was allowed to rise. The control group
      received 12 ml/kg tidal volume with rate adjusted for normocarbia. PEEP and
      fractional inspired oxygen (FIO2) were adjusted to maintain, PaO2 between 8 and
      13.3 kPa (60 and 100 mm Hg) using a predetermined protocol. At 10 h or following
      death, lung lavage was repeated and lung histology evaluated. MEASUREMENTS AND
      MAIN RESULTS: The mean increase in lavage cell counts and protein concentration
      and hyaline membrane scores were not significantly different between the groups.
      Oxygenation progressively improved more in the study group (p = 0.01 vs control
      for PaO2/FIO2 ratio and alveolar-arterial oxygen tension gradient (AaDO2)). PEEP
      was similar and the mean airway pressure higher in the control group, suggesting
      that this probably resulted from less ventilator-induced injury in the study
      group. Four deaths occurred in the control group (three due to pneumothorax and
      one to hypoxaemia) and none in the study group (p = 0.08). CONCLUSIONS: This
      ventilatory protocol may have failed to prevent lung overdistension or it may
      have provided insufficient PEEP to prevent injury in this model; PEEP greater
      than the lower inflection point of the pressure-volume curve has been shown to
      prevent injury almost entirely.

PMID- 8986503
TI  - Prostacyclin counteracts the increase in capillary permeability induced by tumour
      necrosis factor-alpha.
AB  - OBJECTIVE: To analyse how prostacyclin interferes with the short-term local
      circulatory effects of tumour necrosis factor-alpha (TNF alpha) in a skeletal
      muscle. DESIGN: An autoperfused sympathectomised cat gastrocnemius muscle
      enclosed in a plethysmograph. INTERVENTIONS: Arterial blood flow, total and
      segmental vascular resistances (large-bore arterial vessels, arterioles and
      veins), hydrostatic capillary pressure, tissue volume and capillary filtration
      coefficient were followed during local intra-arterial infusion of TNF alpha at
      various rates (2.5, 5.0 and 7.5 micrograms/kg per min) and during intra-arterial
      infusion of prostacyclin simultaneously with the highest dose of TNF alpha. The
      capillary filtration coefficient reflects the capillary surface for fluid
      exchange. RESULTS: Arterial infusion of TNFx had no influence on vascular
      resistance up to 5.0 micrograms/kg per min but induced vasodilation at 7.5
      micrograms/kg per min. No effects on the recorded hydrostatic capillary pressure
      were observed. The capillary filtration coefficient and the capillary filtration
      increased with the infusion rate of TNF alpha, the former by 55%. Simultaneous
      arterial infusion of prostacyclin (350 ng/kg per min) caused further vasodilation
      and an increase in hydrostatic capillary pressure and completely restored the
      capillary filtration coefficient to control. The TNF alpha-induced filtration was
      partly restored. CONCLUSIONS: The local circulatory effect of TNF alpha is small
      apart from a graded increase in the capillary filtration coefficient, most likely
      reflecting an increase in the capillary permeability. The prostacyclin-induced
      decrease in capillary filtration coefficient most likely reflects a restoration
      of capillary permeability. The TNF alpha-induced transcapillary filtration is not
      fully reduced by prostacyclin due to a simultaneous increase in hydrostatic
      capillary pressure.

PMID- 8986504
TI  - Neurological failure in a patient with fat embolism demonstrating no lung
      dysfunction.

PMID- 8986505
TI  - Cardiac aspergillosis: importance of transesophageal echocardiography.

PMID- 8986506
TI  - Acute metabolic acidosis in chronic alcoholism: ketoacidosis as differential
      diagnosis.

PMID- 8986507
TI  - Near fatal case of self-poisoning with thioridazine.

PMID- 8986508
TI  - Bouhaja et al., Intensive Care Med (1994) 20:307-308.

PMID- 8986509
TI  - The effect of a closed system suctioning on airway pressure in an experimental
      mode.

PMID- 8986510
TI  - Predictors for deterioration of respiratory function.

PMID- 8986511
TI  - Tidal volume in acute respiratory distress syndrome.

PMID- 8986512
TI  - Does early intervention improve the prognosis in anorexia nervosa? A systematic
      review of the treatment-outcome literature.
AB  - OBJECTIVE: Early intervention has been suggested to be an important positive
      prognostic factor in the treatment of anorexia nervosa (AN). The treatment
      outcome studies conducted thus far were systematically reviewed in search of
      evidence to confirm this suggestion. METHOD: An extensive search was conducted
      for treatment outcome studies specifically addressing the prognostic value of the
      duration of the illness. Thirty-three follow-up studies of eating disorders and
      AN in particular were subjected to nine "best-evidence" criteria for
      methodological soundness. Six of these studies were found to meet all of the
      criteria and thus considered in greater detail. RESULTS: In four of these
      studies, the duration of illness was not found to be related to the treatment
      outcome. This is presumably because of the low variability in duration of illness
      found in these studies. In the two remaining studies, a negative relation between
      duration of illness and the outcome of treatment was reported. As a result of
      methodological shortcomings and a lack of control for potentially confounding
      variables, however, the prognostic value of early intervention could still not be
      estimated on the basis of these studies. DISCUSSION: The prognostic value of
      early intervention in AN cannot be estimated on the basis of the treatment
      outcome literature. Unfortunately, the duration of the illness and not the
      occurrence of early intervention is considered in most of the outcome studies of
      AN. In addition, a number of methodological shortcomings make it impossible to
      evaluate the prognostic value of early intervention.

PMID- 8986514
TI  - Childhood sexual abuse and precursors of binge eating in an adolescent female
      population.
AB  - OBJECTIVE: We examined the cross-sectional association between childhood sexual
      abuse (CSA) and self-reported binge eating in an adolescent female population.
      METHODS: Study subjects were recruited from clinics specializing in the treatment
      of CSA, and control subjects were from high schools in the same cities. Height
      and weight were measured and subjects completed four questionnaires pertaining to
      binge eating, depression, locus of control, and self-esteem. RESULTS: Study
      subjects showed significantly higher depression, external locus of control, and
      binge eating, and significantly lower self-esteem and weight satisfaction scores
      than did control subjects. After adjusting for all covariables simultaneously,
      CSA was not an independent correlate of binge eating score. The strongest
      correlates of binge eating score in the multivariable analysis were depression,
      body mass index (BMI), and weight satisfaction. CONCLUSIONS: Psychological
      factors such as depression or weight satisfaction were more influential than is
      sexual abuse per se in the relationship between CSA and eating disorders.

PMID- 8986513
TI  - Predictors of outcome for two treatments for bulimia nervosa: short and long
      term.
AB  - OBJECTIVE: This study examined pretreatment variables to predict outcome in two
      treatments for bulimia nervosa. METHOD: Patients were offered either 16 weeks of
      cognitive-behavioral therapy (CBT) or a self-treatment manual followed by up to 8
      weeks of CBT (sequential group). Using complete data, stepwise regression
      analyses were performed. RESULTS: It was found that a longer duration of illness
      and lower binge frequency predicted a better outcome both at the end of treatment
      (p < .001) and at 18 months of follow-up (p < .005). In the sequential group,
      lower pretreatment binge frequency predicted better outcome at the end of
      treatment (p < .05) and at 18 months of follow-up (p < .05). In the CBT group,
      longer duration of illness predicted better outcome at the end of treatment (p <
      .02). DISCUSSION: It is concluded that (1) those with more frequent binging may
      require a more intense intervention and (2) those who have been ill longer may be
      more motivated to respond to treatment.

PMID- 8986515
TI  - Social support in patients with anorexia nervosa and bulimia nervosa.
AB  - OBJECTIVE: To investigate the social support networks of patients with anorexia
      nervosa (AN) and bulimia nervosa (BN). METHOD: Social support was measured using
      the Significant Others Scale for 44 patients with AN, 81 patients with BN, and 86
      polytechnic students. RESULTS: Eating disorder patients had smaller social
      networks than the students. AN patients were significantly less likely than BN
      patients to have a spouse or partner as a support figure. Both AN and BN patients
      reported less actual emotional and practical support than students. AN patients
      perceived their social support to be adequate, whereas BN patients were
      dissatisfied with their support. Patients set lower ideals for support than the
      students. Social support was not correlated with duration of illness. DISCUSSION:
      AN and BN patients have deficient social networks. In BN patients there is
      disturbance in both the size and perceived adequacy of social relationships.

PMID- 8986516
TI  - Self-esteem, eating problems, and psychological well-being in a cohort of
      schoolgirls aged 15-16: a questionnaire and interview study.
AB  - OBJECTIVE: This study aimed to investigate the extent of eating problems and
      their association with self-esteem in girls aged 15-16. METHOD: Six hundred and
      nine schoolgirls aged 15-16 completed a questionnaire examining eating behavior,
      self-esteem, and general psychological well-being. A subsample of 31 girls was
      subsequently interviewed in terms of eating behavior and self-esteem. RESULTS:
      The questionnaire findings revealed that 56% of girls felt too fat and had used
      some form of weight control strategy. In addition, 32% scored above the Hospital
      Anxiety and Depression Scale (HADS) threshold for anxiety and 43% reached the
      Rosenberg Self-Esteem Scale criterion for low self-esteem. Interviews confirmed
      that those showing abnormal eating behavior in the questionnaires did indeed show
      greater eating pathology as well as lower self-esteem. Interviews also revealed
      that those with high levels of eating concern showed greater levels of global
      self-dissatisfaction and higher dissatisfaction with their physical appearance
      and family relationships. DISCUSSION: The results suggest that preventative
      interventions targeted at girls with low self-esteem may be appropriate.

PMID- 8986517
TI  - Comparison of men and women with binge eating disorder.
AB  - OBJECTIVE: This study examined gender differences in individuals with binge
      eating disorder (BED) on eating-related psychopathology and general psychological
      functioning. METHOD: Subjects were age-matched men (n = 21) and women (n = 21)
      with BED who were administered the Eating Disorders Examination (EDE), the
      Structured Clinical Interview for DSM-III-R (SCID) and SCID II, and who completed
      the Emotional Eating Scale (EES) and other questionnaires regarding psychological
      functioning. RESULTS: Men and women did not differ on measures of eating
      disturbance, shape and weight concerns, interpersonal problems, or self-esteem,
      but more men than women met criteria for at least one Axis I diagnosis and had a
      lifetime diagnosis of substance dependence. Women were more likely to report
      eating in response to negative emotions, particularly anxiety, anger and
      frustration, and depression. DISCUSSION: Results from our study suggest that
      while men and women presenting for treatment for BED are very similar, males may
      have more Axis I psychiatric disturbance and less emotional eating than their
      female counterparts. These findings are discussed in terms of the role of gender
      in BED and possible treatment implications are explored.

PMID- 8986518
TI  - Age of onset for binge eating: are there different pathways to binge eating?
AB  - OBJECTIVE: In examining individuals with binge eating disorder (BED), we aimed to
      determine whether their binge eating preceded their first diet or their first
      diet preceded their binge eating, the age of their first diet, the age of their
      first binge, and the age when they met DSM-IV criteria for BED. Additionally, we
      aimed to identify psychological factors that may distinguish the two groups.
      METHODS: Eighty-seven individuals with BED (19 men and 68 women) were
      administered the Eating Disorders Examination, the Structured Clinical Interview
      for DSM-III-R, and several other measures of psychological functioning and
      psychiatric disturbance. RESULTS: Forty-five percent of the subjects reported
      that dieting preceded their first binge episode (dietfirst) and 55% reported that
      binge eating preceded their first diet (bingefirst). There were no significant
      differences in current eating disturbance, body mass index (BMI), or age for
      these two groups, but they differed on the age of the first episode of binge
      eating and the age when binging met BED criteria. The group reporting having
      binged first had a younger age of onset of binge eating and a younger age at
      which binge eating met diagnostic criteria than the dietfirst group. The
      bingefirst group also had a history of more psychiatric problems and were more
      likely to have an Axis II personality disorder. DISCUSSION: Age of onset of the
      first binge and BED is markedly different depending on whether an individual
      began dieting or binging first. These findings suggest that there may be
      important etiological differences between individuals who binge first and those
      who diet first. Moreover, individuals who binge first may be at greater risk for
      psychiatric disturbance.

PMID- 8986519
TI  - Global self-esteem as contingent on body satisfaction among patients with bulimia
      nervosa: lack of diagnostic specificity?
AB  - OBJECTIVE: To examine whether the self-esteem of patients with bulimia nervosa
      was more contingent on body satisfaction than that of nonpsychiatric control and
      of depressed participants. METHODS: Patients with bulimia nervosa (selected
      according to DSM-III-based structured clinical interviews), those with depression
      (selected based on chart diagnoses), and nonpsychiatric control samples completed
      measures of body dissatisfaction and of global self-esteem. RESULTS: Consistent
      with past work, we found that body dissatisfaction accounted for a greater amount
      of global self-esteem among bulimia nervosa patients, as compared to
      nonpsychiatric control subjects. However, the relation between global self-esteem
      and body dissatisfaction was similar in patients with bulimia nervosa as in those
      with depression. Although our depressed group possessed bulimic characteristics,
      this did not appear to account for our findings, in that the correlation between
      body dissatisfaction and self-esteem was highest among the nonbulimic depressed
      participants. DISCUSSION: Our results raise questions about the specific
      pathognomonic quality of body satisfaction-dependent self-esteem in bulimia
      nervosa.

PMID- 8986520
TI  - Impaired color naming of food and body shape words: weight phobia or distinct
      affective state?
AB  - OBJECTIVE: The current study investigated whether a concern with body shape and
      weight represents a distinct affective state, or whether it is better
      conceptualized as a highly specific form of anxiety. METHOD: The color-naming
      performance of women with a high Drive for Thinness score was examined under
      three experimental conditions: when a photograph of chocolate was present, when
      actual chocolate was present, and a control condition. High Drive for Thinness
      subjects demonstrated relatively impaired color naming of body shape words in the
      picture condition, but not in the food or control conditions. RESULTS: Although
      there was a significant impairment in the color naming of food words, this was
      unaffected by condition or degree of Drive for Thinness. DISCUSSION: The results
      are interpreted as supporting an analogy between weight/body shape concerns and
      subclinical phobic anxiety.

PMID- 8986521
TI  - Obsessive compulsive comorbidity in the dieting disorders.
AB  - OBJECTIVE: This study investigated the comorbidity of obsessive compulsive
      disorder and obsessive compulsive personality disorder with the dieting
      disorders. A comorbid sample was examined in order to test the hypothesis that
      obsessive compulsive symptoms and personality are premorbid in these patients.
      METHOD: Sixty-eight inpatients (35 with anorexia nervosa and 33 with bulimia
      nervosa) were assessed for DSM-III-R Axis 1 and Axis 11 obsessive compulsive
      psychopathology using the Composite International Diagnostic Interview (CIDI) and
      the Personality Disorders Inventory (PDE), respectively. RESULTS: Twenty-one
      percent of the group met criteria for a diagnosis of obsessive compulsive
      disorder. Thirty-seven percent of anorexia nervosa patients were comorbid for
      obsessive compulsive disorder compared to only 3% of bulimia nervosa patients. In
      most, the obsessive compulsive disorder had predated the dieting disorder.
      Nineteen percent of patients were found to have premorbid obsessive compulsive
      personality disorder. DISCUSSION: This study supports the assumption of obsessive
      compulsive comorbidity within the dieting disorders and provides empirical
      support that this obsessionality is a premorbid characteristic.

PMID- 8986522
TI  - Appraisal and coping strategies in stressful situations: a comparison of
      individuals who binge eat and controls.
AB  - OBJECTIVE: The objective of this study was to investigate whether individuals who
      engage in binge eating appraise and cope with stressful situations in a different
      manner than people who do not regularly binge eat. METHOD: Female undergraduates
      participated in a two-part study. The laboratory portion of the study involved
      participation in two tasks: an interpersonal stressor and an academic stressor.
      In the second portion of the study, participants completed a daily stress
      inventory for 1 week. RESULTS: Individuals in the binge group appraised both the
      laboratory and natural environment stressors as more stressful than did the
      controls. Differences were evident in the amount and type of coping strategies
      used between eating groups. The binge group reported using more positive coping
      strategies and more catastrophizing in both settings. DISCUSSION: Together, the
      results suggest that appraisal and coping or stress management components may be
      useful in treatment packages for individuals who binge eat.

PMID- 8986523
TI  - Serum electrolytes as markers of vomiting in bulimia nervosa.
AB  - OBJECTIVE: Patients with bulimia nervosa often have serum electrolyte
      abnormalities that result from vomiting and/or laxative or diuretic use. Thus,
      serum electrolytes could serve as an objective marker of such behaviors. METHOD:
      This study is a retrospective examination of serum electrolyte levels and
      vomiting behavior in 138 bulimic women, and of serum electrolyte levels in 70
      control women. RESULTS: Logistic regression analyses demonstrated that only
      potassium values distinguished bulimic subjects from controls. Potassium levels
      below the lower limit of normal (3.7 mg/l) occurred only in the bulimic group.
      DISCUSSION: Abnormally low values for potassium are a specific, but not
      sensitive, predictor of recent vomiting episodes.

PMID- 8986524
TI  - Clinical features of binge eating disorder in type I diabetes: a case report.
AB  - Eating disorders in patients with type I diabetes show some peculiar clinical
      features. We report the case of a young type I diabetic woman with binge eating
      disorder and dysthymic disorder. The patient shows a poor metabolic control and
      her body mass index is within the normal range. The eating disorder has been
      present for 3 years, and it developed after recurrent nocturnal hypoglycemic
      episodes. The authors discuss the complex relationships between binge eating
      disorder and hypoglycemic reactions and underline the diagnostic problems typical
      of comorbidity between type I diabetes and binge eating disorder.

PMID- 8986525
TI  - Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma
      peritonei in women.
AB  - Women with pseudomyxoma peritonei (PMP), characterized by multifocal mucinous
      implants (disseminated peritoneal adenomucinosis), often have synchronous
      appendiceal and ovarian mucinous tumors. There has been considerable debate as to
      whether the ovarian tumors are secondary to the appendiceal tumor or are
      independent primary ovarian tumors; the latter are usually classified as mucinous
      tumors of low malignant potential (MLMP). It has been reported that cytokeratins
      (CK) 7, 18, and 20, carcinoembryonic antigen (CEA), and human alveolar macrophage
      56 (HAM-56) are useful markers for distinguishing primary ovarian neoplasms from
      metastases of intestinal origin. Nearly all primary ovarian MLMP tumors and
      mucinous carcinomas are positive for CK 7, 18, and 20, CEA, and HAM-56, whereas
      most colorectal adenocarcinomas are negative for both CK 7 and HAM-56 and
      positive for CK 20 and CEA. Thirteen appendiceal and 14 ovarian mucinous tumors
      from 14 cases of PMP and 11 primary ovarian MLMP tumors were studied
      immunohistochemically for expression of CK 7, 18, and 20, monoclonal and
      polyclonal CEA (mCEA and pCEA), and HAM-56. Of 14 cases of PMP, 10 (71.4%) had
      identical staining patterns for all antibodies in both the appendiceal and
      ovarian tumors. For eight of these, the pattern of immunoreactivity was
      characterized by negative reactions for CK 7 and HAM-56 and positive reactions
      for CK 18 and 20, mCEA, and pCEA. One additional case for which only the ovarian
      tumor could be stained had the same pattern. The remaining two cases were also
      positive for CK 18 and 20 and CEA, but in addition were positive for CK 7. Two
      cases were discordant only for CK 7 and one case was discordant for both CK 7 and
      HAM-56. All 11 MLMP tumors were positive for CK 7 and 18, and pCEA. Eight (72.7%)
      of 11 were positive for HAM-56, mCEA, and CK 20. There was a statistically
      significant difference in the frequency of immunoreactivity for CK 7 (p = 0.0005)
      and HAM-56 (p = 0.0002) between the ovarian mucinous tumors in PMP and the MLMP
      tumors, with the ovarian tumors in PMP tending to be negative for CK 7 and HAM
      56, similar to the appendiceal adenomas. Most ovarian mucinous tumors in PMP
      demonstrate a pattern of immunoreactivity with CK 7, 18, and 20, CEA, and HAM-56
      that is identical to the associated appendiceal adenoma and distinct from primary
      ovarian MLMP tumors, consistent with the interpretation that these ovarian tumors
      are secondary to the appendiceal tumor.

PMID- 8986526
TI  - Human papillomavirus type influences the extent of chromosomal lag during mitosis
      in cervical intraepithelial neoplasia grade III.
AB  - The level of risk for carcinoma in the uterine cervix depends on the type of
      human papillomavirus (HPV) present. We examined whether the HPV type influences
      the proliferation rate and occurrence of mitotic figures with lagging chromosomes
      in the precursor of cervical carcinoma. The study group comprised 180 women who
      were referred because of cytologic changes indicating dysplasia and who were
      subsequently diagnosed with cervical intraepithelial neoplasia grade III. The HPV
      16-associated lesions showed a significantly higher number of mitoses per 1,000
      nuclei than the lesions without HPV (p < 0.001). The HPV-16-associated lesions
      also showed a significantly higher proportion of mitotic figures with lagging
      chromosomes than did the HPV-18- or HPV-31-associated lesions and lesions without
      HPV (p = 0.01, p = 0.007, and p = 0.002, respectively). Our results indicate that
      the differences in oncogenic potential among HPVs become apparent in the
      precursor lesion through the differences in the extent of chromosomal lag during
      mitosis.

PMID- 8986527
TI  - Quantitative image analysis of MIB-1 reactivity in inflammatory, hyperplastic,
      and neoplastic endocervical lesions.
AB  - The diagnosis of endocervical neoplasia can be difficult as it is sometimes
      mimicked by proliferative or reactive glands. MIB-1 is a proliferation marker
      that can aid in the diagnosis of squamous intraepithelial lesions (SIL) of the
      cervix and vulva, but its potential value in the diagnosis of endocervical
      lesions has not been fully explored. Ten formalin-fixed, paraffin-embedded cases
      of each of the following were obtained: morphologically normal endocervical
      glands from patients with cervical SIL, endocervicitis, microglandular
      hyperplasia (MGH), and endocervical adenocarcinomas (eight in situ, two
      invasive). Microwave unmasking of antigens was performed prior to
      immunohistochemical staining for MIB-1 using the avidin/biotin peroxidase method.
      Labeling indexes were calculated for 34 specimens (10 adenocarcinoma. 8 each of
      the other diagnoses) using image analysis (Samba 4000). There was diffuse MIB-1
      reactivity in adenocarcinoma (labeling index 57-96%, mean 80%), minimal focal
      reactivity in normal glands underlying SIL (labeling index 0.8-4.3%, mean 2.4%),
      moderate spotty reactivity in MGH (labeling index 2.9-18.4%, mean 8.5%), and
      minimal to focally diffuse reactivity in endocervicitis (labeling index 1.0
      13.3%, mean 5.7%). These data indicate that the percentage and distribution of
      MIB-1-reactive endocervical cells can be of diagnostic utility in distinguishing
      neoplastic glands from those of endocervicitis and MGH.

PMID- 8986529
TI  - Chorionic villi or trophoblastic tissue in uterine samples of four women with
      ectopic pregnancies.
AB  - The diagnosis of early ectopic pregnancy remains challenging for the
      gynecologist. Although early detection of a suspected pregnancy has been
      facilitated by quantitative beta human chorionic gonadotropin studies and
      ultrasonography, a patient subgroup remains with an ambiguous presentation. In
      this group of patients, the clinician must rely on microscopic examination of
      products of conception in a uterine curettage specimen to rule out the presence
      of an extrauterine pregnancy. The presence of an implantation site, chorionic
      villi, or trophoblastic tissue in uterine curettage samples is conventionally
      held as definitive evidence of an intrauterine pregnancy. We present a series of
      four cases that challenge this convention. In these cases, chorionic villi or an
      implantation site were identified in uterine samples of pregnant women who each
      ultimately proved to have an ectopic pregnancy. If clinical suspicion is high,
      the finding of either chorionic villi or an implantation site should not preclude
      further workup of a possible ectopic pregnancy. In cases where only a few villi
      or a single chorionic villus are identified, other signs of intrauterine
      implantation such as intermediate trophoblastic cells, hyalinized vessels, and a
      fibrinoid matrix should be sought to establish firmly the diagnosis of an
      intrauterine pregnancy.

PMID- 8986528
TI  - Immunohistochemical detection of p53 and bcl-2 proteins in neoplastic and non
      neoplastic endocervical glandular lesions.
AB  - The study examines p53 and bcl-2 protein expression in a variety of neoplastic
      and non-neoplastic endocervical glandular lesions. Immunohistochemical staining,
      using monoclonal antibodies against p53 (DO-7) and bcl-2, was performed on
      archival paraffin-embedded tissue following microwave antigen retrieval. With DO
      7 there was positive nuclear staining in 23/33 cases of adenocarcinoma, 2/10
      adenocarcinoma in situ, 2/10 tubo-endometrial metaplasia, 1/10 microglandular
      hyperplasia, and 1/17 normal endocervix. With adenocarcinoma in situ and non
      neoplastic lesions, positive staining was confined to scattered cells. Nine of 23
      positive cases of adenocarcinoma showed widespread staining. With anti-bcl-2
      antibody, there was positive cytoplasmic staining in 9/33 cases of
      adenocarcinoma, 0/10 adenocarcinoma in situ, 7/10 tubo-endometrial metaplasia,
      1/10 microglandular hyperplasia, and 0/17 normal endocervix. Five of nine
      positive adenocarcinomas showed widespread staining. There was widespread
      positive staining for bcl-2 in six of seven positive cases of tubo-endometrial
      metaplasia. The results indicate that p53 protein expression is frequent in
      endocervical adenocarcinoma and suggest that mutation of the p53 gene may be
      important in the evolution of some cases of endocervical adenocarcinoma.
      Scattered p53-positive cells may be seen in endocervical adenocarcinoma in situ
      and in non-neoplastic endocervical glandular lesions, the significance of which
      is uncertain. Bcl-2 protein expression is seen in a proportion of endocervical
      adenocarcinomas and may play a role in the evolution of these tumors through
      inhibition of apoptosis. Widespread positivity for bcl-2 protein is seen in most
      cases of tubo-endometrial metaplasia, suggesting that this type of metaplastic
      epithelium may represent an unusually stable population of cells.

PMID- 8986530
TI  - Comparison of the reproducibility of the WHO classifications of 1975 and 1994 of
      endometrial hyperplasia.
AB  - In a blinded, randomized design, six histopathologists with an interest in
      gynecological pathology examined the inter- and intraobserver variation of the
      histopathological diagnosis of endometrial hyperplasia according to the World
      Health Organization (WHO) classification of 1975 and the new WHO classification
      of 1994. On four occasions, the pathologists assessed hematoxylin/eosin-stained
      slides from 128 cases originally diagnosed and coded in the Snomed system as
      endometrial hyperplasia. In the first and third rounds, the slides were
      classified according to the 1975 classification and in the second and fourth
      rounds according to the 1994 classification. The overall interobserver agreement
      in the two rounds where the 1975 classification was used was 0.47 and 0.51, and
      the kappa values 0.24 [95% confidence interval (CI) 0.21-0.27] and 0.30 (95% CI
      0.27-0.33). The overall interobserver agreement in the two rounds using the 1994
      classification was 0.45 and 0.41 and the kappa values 0.25 (95% CI 0.23-0.28) and
      0.20 (95% CI 0.17-0.22). Reducing the classification to two categories with
      clinical significance (atypical endometrial hyperplasia versus others in the 1975
      classification, and atypical endometrial hyperplasia, complex versus others in
      the 1994 classification) increased the overall agreement of the 1975
      classification in both rounds to 0.91 and of the 1994 classification to 0.92 and
      0.90. The kappa values increased to 0.54 (95% CI 0.49-0.58) and 0.49 (95% CI 0.45
      0.54) in the 1975 classification and to 0.59 (95% CI 0.54-0.63) and 0.42 (95% CI
      0.37-0.46) in the 1994 classification. The intraobserver overall agreement for
      the 1975 classification ranged from 0.80 to 0.55 and the kappa values from 0.70
      (95% CI 0.58-0.81) to 0.28 (95% CI 0.17-0.39). The intraobserver overall
      agreement for the 1994 classification ranged from 0.71 to 0.46 and the kappa
      values from 0.60 (95% CI 0.51-0.70) to 0.20 (95% CI 0.09-0.30). It is concluded
      that there is considerable inter- and intraobserver variation using both the 1975
      and the 1994 classifications of endometrial hyperplasia. We propose that there is
      need for a specification and for a simplification of the classification.

PMID- 8986531
TI  - Tumors of the uterine isthmus: clinicopathologic features and immunohistochemical
      characterization of p53 expression and hormone receptors.
AB  - Five (3%) of 161 endometrial cancers treated surgically between 1988 and 1992
      were classified as primary isthmic tumors, and their clinicopathologic features,
      p53 expression, and hormone receptor status were evaluated. Three were
      endometrioid adenocarcinomas with squamous differentiation, one was a mixed
      serous and clear cell carcinoma, and one was a malignant mullerian mixed tumor;
      all five were high grade, invaded the entire thickness of the myometrium, and
      exhibited lymphatic space invasion. Four of the five patients had extrauterine
      metastases identified at the time of hysterectomy. All five patients died due to
      progressive disease with the survival time ranging from 1 to 23 months. Abnormal
      p53 gene expression was identified immunohistochemically in three of the five
      isthmic tumors. Weak positivity for estrogen and progesterone receptors was
      demonstrated in one case, with the remaining four being negative. Tumors arising
      in and confined to the uterine isthmus are unusual and, in our series, were
      uniformly aggressive with an unfavorable prognosis. The histopathologic features
      and biologic behavior of the isthmic tumors appeared similar to those of other
      high-grade endometrial cancers arising in the uterine corpus.

PMID- 8986532
TI  - Expression of fatty acid synthase is closely linked to proliferation and stromal
      decidualization in cycling endometrium.
AB  - Estrogen-driven proliferative phase growth is the most rapid physiological
      proliferative process that occurs in the adult. The tissue growth that occurs
      during this phase of the menstrual cycle requires incorporation of a substantial
      quantity of fatty acid into the structural lipids of cell membranes. Fatty acid
      synthase (FAS) is the major biosynthetic enzyme required for de novo synthesis of
      fatty acids. In this immunohistochemical study, we have observed that human
      endometrium displays distinct patterns of FAS expression in the proliferative and
      secretory phases of the normal menstrual cycle. Proliferative endometrial glands
      and stroma show high FAS expression that closely correlates with expression of Ki
      67, estrogen and progesterone receptors, supporting the view that FAS expression
      plays a role in cellular proliferation in response to estrogen. FAS expression
      declines during early to midsecretory phase, then reappears in decidualized
      stromal cells in late secretory phase as well as in the decidua of pregnancy. The
      second wave of FAS expression correlates with progesterone-receptor localization
      in the decidual cells, a finding suggesting a second induction of FAS expression
      in the endometrium, associated with differentiation, that may be regulated by
      progesterone.

PMID- 8986533
TI  - Microglandular adenocarcinoma of the endometrium: a form of mucinous
      adenocarcinoma that may be confused with microglandular hyperplasia of the
      cervix.
AB  - Microglandular adenocarcinoma of the endometrium may cause diagnostic problems
      because of its bland cytologic appearance and its histologic similarity to benign
      microglandular hyperplasia of the cervix. We present two cases of microglandular
      adenocarcinoma and discuss the clinical, pathologic, and immunohistochemical
      findings. Both patients were postmenopausal women, one of whom was taking
      exogenous hormones. Endometrial biopsy specimens contained polypoid tissue
      fragments, within which were microcystic spaces lined by flattened, cuboidal, or
      columnar cells. Solid nests or sheets of tumor cells surrounded glands in some
      tissue fragments. The nuclei were uniform and bland, and mitotic figures,
      although readily identifiable, were infrequent (1 per 10 high-power fields). A
      majority of tumor cells contained intracytoplasmic mucin. Numerous neutrophils
      were present in gland lumens and tissues. Immunohistochemical stains for
      carcinoembryonic antigen and TAG72 (B72.3) revealed focal moderate to intense
      apical and cytoplasmic staining; immunostains for p53 protein were negative. One
      carcinoma was confined to the endometrium, whereas the other invaded into the
      inner one-third of the myometrium. Both patients were well after a limited follow
      up of 1 year. Microglandular adenocarcinoma is a distinctive variant of
      endometrial carcinoma that is most likely a form of mucinous adenocarcinoma.

PMID- 8986534
TI  - Expression of epidermal growth factor-related proteins and epidermal growth
      factor receptor in common epithelial ovarian tumors.
AB  - The biologic significance of epidermal growth factor (EGF)-related proteins and
      EGF receptor (EGFR) in the development and progression of human ovarian carcinoma
      was studied in 7 ovarian cystadenomas, 6 mucinous tumors of low malignant
      potential (LMP), and 25 invasive adenocarcinomas by immunohistochemistry. Results
      were correlated with clinicopathologic features. We also examined
      immunoreactivity in five serous adenocarcinomas both before and after cisplatin
      chemotherapy. Amphiregulin (AR) expression was observed only in mucinous tumors
      (4 of 8 cystadenomas, 2 of 6 tumors of LMP, and 6 of 10 cystadenocarcinomas), but
      was not detected in the serous tumors or clear cell adenocarcinomas. EGF, cripto,
      and EGFR expression was significantly higher in mucinous cystadenocarcinomas than
      in mucinous cystadenomas or mucinous tumors of LMP. Three of five specimens
      obtained at a second operation after chemotherapy had more intense or diffuse
      immunostaining for transforming growth factor alpha (TGF-alpha) than the initial
      specimens did. Coexpression of more than two of the EGF-related proteins or EGFR
      significantly correlated with increased surgical stage in serous and clear cell
      carcinoma. AR expression seems to correlate with mucinous differentiation rather
      than with advanced stages of ovarian tumors. Our results indicate that expression
      of some EGF-related proteins is greater in certain subtypes of ovarian carcinomas
      than in their benign counterparts and that coexpression of these proteins is
      associated with advanced stage in serous and clear cell carcinoma. Increased TGF
      alpha expression may also be related to ovarian tumor resistance to cisplatin
      chemotherapy.

PMID- 8986535
TI  - P-glycoprotein as a prognostic indicator in pre- and postchemotherapy ovarian
      adenocarcinoma.
AB  - P-glycoprotein (P-gp) is a plasma membrane efflux transporter that maintains the
      intracellular concentration of chemotherapeutic agents at low levels. Since the
      clinical outcome of ovarian adenocarcinoma depends largely on its response to
      chemotherapy, an objective assessment of P-gp expression could serve as a
      prognostic indicator. Eighty-five patients were studied. Available tissue
      sections from the primary tumor (n = 75) and persistent or recurrent lesions (n =
      19) were tested with anti-P-gp (JSB-1) monoclonal IgG. Multivariate survival
      analysis using Cox regression was performed controlling for fixed covariates
      (age, surgical stage, and presence of residual tumor) and included occurrence of
      postchemotherapy tumors and P-gp positivity in postchemotherapy neoplasms as time
      dependent variables. P-gp was expressed in 49 prechemotherapy (65.3%) and 14
      postchemotherapy (73.7%) tumors. After controlling for potentially confounding
      factors, patients with P-gp-positive postchemotherapy neoplasms were at three
      times greater risk of dying within 2 years than their counterparts with P-gp
      negative tumors (hazard ratio = 3.1: 95% confidence interval = 1.2, 9.1; p <
      0.05). Detection of P-gp-expressive subclones can serve as an independent poor
      prognostic indicator for patients with postchemotherapy tumors.

PMID- 8986536
TI  - Osteosarcoma metastatic to the ovary: a case report and review of the literature.
AB  - A 23-year-old black woman presented with abdominal pain of sudden onset, high
      fever, chills, and an elevated serum alkaline phosphatase level. Examination
      revealed a tender abdominopelvic mass consistent with an ovarian mass. Her
      medical history was significant for an osteosarcoma of the left humerus removed 7
      years earlier and excision of multiple pulmonary and chest wall metastases 2
      years earlier. Exploratory laparotomy revealed a solid hemorrhagic left ovarian
      mass and ascites. There was no other evidence of disease. A left salpingo
      oophorectomy was performed. Pathological examination of the mass showed
      metastatic osteosarcoma. Four months later, the patient died of widespread
      osteosarcoma. The clinicopathologic features of ovarian osteogenic sarcomas
      reported in the literature are reviewed. Pain, fever, and elevated serum alkaline
      phosphatase levels may be the presenting clinical features of this rare ovarian
      tumor.

PMID- 8986537
TI  - Clear cell hyperplasia of the fallopian tube epithelium associated with ectopic
      pregnancy: report of a case.
AB  - A case of clear cell hyperplasia of the fallopian tube epithelium associated with
      ectopic pregnancy is described. The lesion was encountered in a 31-year-old woman
      who presented with abdominal pain and had a positive pregnancy test. Ultrasound
      examination disclosed an enlarged right fallopian tube. The patient underwent
      laparotomy, at which time the right fallopian tube was excised. On gross
      examination, a firm, 1.2 x 1 x 1-cm nodule almost obliterating the lumen of the
      tube and an abundant blood clot were present. On histologic examination,
      chorionic villi were found in the blood clot. The nodule was composed of
      epithelial cells that formed solid and glandular structures. The cells had clear
      cytoplasm and nuclei without atypia. The differential diagnosis included clear
      cell adenocarcinoma, but clear cell hyperplasia associated with pregnancy was
      diagnosed because of the absence of cytologic atypia and mitotic figures. The
      patient has had an uneventful postoperative follow-up period of 1 year.

PMID- 8986538
TI  - History of gynecological pathology. II. Dr. William H. Sternberg.

PMID- 8986539
TI  - Oral surgery.

PMID- 8986541
TI  - Closed reduction of chronic bilateral temporomandibular joint dislocation. A case
      report.
AB  - Attempts at manual reduction under general anesthesia of a chronically dislocated
      temporomandibular joint were unsuccessful. Light elastic traction was applied to
      modified dentures, and after 7 weeks the condyles were partially repositioned.
      Without further active reduction, the condyles were fully reseated by 9 months.

PMID- 8986540
TI  - The vascular anatomy of the human temporalis muscle: implications for surgical
      splitting techniques.
AB  - Despite the wide application of the temporalis muscle flap and its modifications,
      understanding of the vascular pattern and territories within the muscle remains
      poor. This study aimed to evaluate the vascular architecture in the human
      temporalis muscle for surgical application. The material comprised 15 fresh
      cadavers (30 muscle specimens), which were divided into three groups for vascular
      infusion by either Indian ink solution, lead oxide solution, or
      methylmethacrylate resin. The vascular network in the temporalis muscle was
      analyzed by stereomicroscopy, radiography, and scanning electron microscopy. The
      human temporalis muscle was found to have vascular supply from three primary
      arteries: the anterior deep temporal artery (ADTA), the posterior deep temporal
      artery (PDTA), and the middle temporal artery (MTA). Each primary artery branched
      into the secondary arterioles and then the terminal arterioles. The venous
      network accompanied the arteries, and double veins pairing one artery was a
      common finding. The capillaries formed a dense, interlacing network with
      orientation along the muscle fibres. Arteriovenous anastomosis was absent. In the
      coronal plane, the vessels were located mainly on the lateral and medial aspects
      of the muscle with a significantly lower vascular density in the midline.
      Morphometric analysis of the arterial network showed that the PDTA was larger in
      size at primary and secondary branching levels than the ADTA and the MTA, whereas
      no differences were present at the terminal arteriolar levels. The distribution
      of the arterial territories was as follows: the ADTA occupied 21% anteriorly, the
      PDTA occupied 41% in the middle region, and the MTA occupied 38% in the posterior
      region. This improved understanding of the vascular architecture within the
      temporalis muscle complements the anatomic basis of the flap-splitting technique
      and increases the safety of its application.

PMID- 8986542
TI  - Horseshoe Le Fort I osteotomy in combination with endosteal implants--a median
      term follow-up study.
AB  - Fourteen patients with Class VI resorption of the maxilla were treated with
      horseshoe Le Fort I osteotomy. In 11 cases, the procedure was followed by the
      placement of endosteal implants. In six patients, simultaneous placement of
      implants was carried out, while in five patients this was done in a second
      procedure. Ten patients wore their implant-supported dentures. In one patient,
      5/8 implants were lost due to nonintegration. Three patients lost one implant
      each. The total number of implants placed was 76, and the survival rate of the
      implants was 88.1%. In the one-step procedure (n = 42), the survival rate was
      84.8%; in the two-step procedure (n = 34), 92.3%. In comparison of the one-step
      to the two-step procedure, there was no statistically significant difference (P >
      0.11) between the amount of marginal peri-implant bone loss and the condition of
      the peri-implant soft tissues as measured 2 years after implantation.

PMID- 8986543
TI  - Fractures of the atrophic, edentulous maxilla during Le Fort I osteotomy.
AB  - The incidence of unfavorable fractures of the maxilla during Le Fort I osteotomy
      was compared between patients with atrophic, edentulous maxillae and patients
      with normal dentate maxillae. Unfavorable fractures frequently occurred in
      atrophic, edentulous maxillae. The most common maxillary fracture involved the
      junction of the horizontal plate of the palatine bone and posterior part of the
      maxilla. Prevention strategies and treatment options are discussed.

PMID- 8986544
TI  - Transmandibular implant versus intramobile cylinder implants: a randomized,
      prospective clinical trial.
AB  - A randomized, controlled clinical trial was conducted to compare two different
      implant treatment modalities for edentulous patients with severely resorbed
      mandibles. In one modality (the IMZ group), two intramobile cylinder implants
      were placed, connected by a Dolder bar and provided with an overdenture, and in
      the other (the TMI group), a transmandibular implant with a triple bar and
      cantilever extensions was placed, likewise provided with an overdenture. The
      conditions of the overdentures, the peri-implant tissues, and the implants were
      evaluated. Orthopantomograms were taken for radiologic evaluation. An overall
      complication scale which took account of all aspects was devised to compare the
      results. The follow-up period was 2-4 years, with a mean follow-up of 3 years.
      The condition of dentures and oral hygiene aspects were comparable for both
      groups. The complication rate in the TMI group was significantly higher than that
      in the IMZ group. The scores on the complication scale resulted in a significant
      difference between the TMI and the IMZ groups (Wilcoxon, P = 0.0044).

PMID- 8986545
TI  - Correlation of imaging and clinical features in the assessment of mandibular
      invasion of oral carcinomas.
AB  - The detection in the mandible of early local spreading of adjacent primary
      malignancies poses a difficult problem. A survey of 60 patients suspected of
      carcinomatous mandibular infiltration was undertaken, and the most important
      clinical and imaging data were studied. Tumor localization and bone scintigraphy
      proved to offer the most important predictive power. A decision tree and a
      logistic regression model which determines a score function combining these
      characteristics were designed. This decision tree improves the sensitivity and
      specificity of the preoperative assessment and provides the surgeon with an
      algorithm for the accurate estimation of early mandibular invasion.

PMID- 8986546
TI  - Oncologic aspects of vermilionectomy in microinvasive squamous cell carcinoma of
      the lower lip.
AB  - Twelve patients with microinvasive squamous cell carcinoma of the lower lip were
      studied in order to determine whether vermilionectomy was justifiable. The
      maximum tumor thickness (MTT) varied between 1.1 and 3.1 mm. In none of the
      patients was there local recurrence during a mean follow-up period of 4.4 years
      (range 4-8). In view of these results and of what has been reported in the
      literature, it seems warranted to conclude that vermilionectomy is an appropriate
      procedure in microinvasive carcinoma of the lower lip with a MTT of up to 3 mm.

PMID- 8986547
TI  - Diagnosis and treatment of branchial cleft cysts and fistulae. A retrospective
      study of 183 patients.
AB  - A retrospective analysis of 183 patients undergoing surgical treatment for
      branchial cleft cysts and fistulae between 1970 and 1990 was carried out. There
      were 148 (80.8%) cases of branchial cleft cysts and 35 (19.2%) cases of branchial
      cleft fistulae. In patients with branchial cysts, the most frequent clinical
      presentation consisted of a left-sided, painless, cervical mass. Patients with a
      branchial fistula presented with persistent mucous discharge from a skin opening
      in the neck. The introduction of ultrasonography, computed tomography, and
      magnetic nuclear resonance imaging has improved the accuracy of traditional
      radiologic methods such as parotid sialography and fistulography. Complete
      excision under general anesthesia is the treatment of choice, and the procedure
      is associated with a low incidence of local complications and neurologic
      sequelae. The overall recurrence rate was 4.9% after a follow-up of 2 years.

PMID- 8986548
TI  - Palatal juvenile xanthogranuloma. A case report.

PMID- 8986549
TI  - Oral myiasis. A case report.
AB  - Myiasis is a disease commonly seen in animals, especially sheep and cattle. The
      condition is rare in man. A patient with a neglected fractured mandible with
      superimposed myiasis is reported.

PMID- 8986550
TI  - Usefulness of fat-suppression magnetic resonance imaging for oral and
      maxillofacial lesions.
AB  - In magnetic resonance imaging (MRI) of the oral and maxillofacial region, where
      large amounts of fat are normally present, the high signal intensity of fat on T1
      weighted images (T1WI) and the chemical-shift artifact have limited the utility
      of paramagnetic contrast agents. Eliminating fat signal by fat-suppression
      techniques can increase the value of contrast-enhanced MRI. The present study was
      designed to evaluate the utility and role of chemical-shift imaging for fat
      suppression in the detection of oral and maxillofacial lesions in 22 patients (17
      with malignant tumors, two with benign tumors, and three with inflammation). The
      depiction of lesions on the postcontrast fat-suppression T1WI was compared with
      that of conventional pre- and postcontrast T1 and T2WI on a four-grade scale
      (grades 0-3). The postcontrast fat-suppression T1WI (average grade, 2.86) were
      significantly superior to the precontrast T1WI (0.82) and postcontrast T1WI
      (1.86) and T2WI (1.68). Postcontrast fat-suppression T1WI were particularly
      beneficial in the detection of central necrosis or extracapsular invasion of
      metastatic neck lymph nodes as well as in defining the lesion extent at fat
      containing areas such as the bone marrow or cheek. These findings demonstrated
      that the fat-suppression technique is extremely useful in the delineation of oral
      and maxillofacial lesions without increase of the scan time or image
      postprocessing procedures.

PMID- 8986551
TI  - In vivo surface analysis of titanium and stainless steel miniplates and screws.
AB  - This study was undertaken to characterize the surfaces of Champy titanium and
      stainless steel miniplates and screws that had been used to stabilize fractures
      of the mandible in an animal model. Miniplates and screws were retrieved at 4,
      12, and 24 weeks after surgery. Low-vacuum scanning electron microscopy (SEM) of
      autoclaved unused (control) and test miniplates from the same production batches
      was undertaken. Energy-dispersive X-ray (EDX) analysis was used to identify
      compositional variations of the miniplate surface, and Vickers hardness testing
      was performed. At autopsy, clinical healing of all fractures was noted. SEM
      analysis indicated no perceptible difference in the surface characteristics of
      the miniplates at all time intervals. Aluminium and silicon deposits were
      identified by EDX analysis over the flat surfaces. There was extensive damage to
      some screw heads. It is concluded that there were no significant changes in the
      surface characteristics of miniplates retrieved up to 24 weeks after implantation
      in comparison with controls. Damage to the screws during insertion due to
      softness of the materials may render their removal difficult. There was no
      evidence to support the routine removal of titanium or stainless steel miniplates
      because of surface corrosion up to 6 months after implantation.

PMID- 8986552
TI  - Fixation with reconstruction plates under critical conditions: the role of screw
      characteristics.
AB  - Mandibular angular ostectomy defects in 12 sheep were bridged with a titanium
      plate system (THORP), designed according to the screw-plate-locking principle.
      Two screw designs (hollow and solid) and two rough (plasma-coated, sand-blasted)
      surface and one smooth (anodized)-surface structure were tested in a critical two
      screw anchorage model. Fixation with two screws only per fragment was successful
      in only one-third of the cases. The fixation results were superior for screws
      with a rough surface, either sand-blasted or plasma-coated. The hollow-screw
      design did not seem to offer special advantages over the solid screws with
      identical surface structure. In the successful cases, the bone-screw contact was
      maintained continuously over a period of 8 weeks, and anchorage was even enhanced
      by reinforcement of the cancellous structures. In the unsuccessful cases, peri
      implant bone resorption seemed to be related to jeopardized bone perfusion in the
      vicinity of the implants. It is presumed that a plating system with locked screws
      has the advantage that only two screws will hold a relatively short condylar
      process. This study proved the assumption to be questionable. However, in view of
      the problems related to prosthetic replacement of the temporomandibular joint, an
      attempt to salvage the articular portion may still be justified in selected
      cases, even if the chance of success is as low as 30%.

PMID- 8986553
TI  - [Bacteriological, pharmacokinetic and clinical evaluation of azithromycin in the
      pediatric field].
AB  - Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules
      was studied for pharmacokinetic and clinical evaluation in the pediatric
      patients. Antibacterial activity of AZM against 43 clinical isolates: AZM
      exhibited slightly lower activity against Gram-positive bacteria and 2-8-fold
      higher activity against Gram-negative bacteria than erythromycin or
      clarithromycin. Plasma or urine samples were collected from eight patients
      receiving the drug in fine granular form, and two patients receiving it in
      capsules for the determination of drug levels. The elimination half-lives of AZM
      after administration at dose of 10 mg/kg/day for 3 days were 50.0 and 51.2 hours
      for fine granules, and 41.5 hours for capsules. AUC0-infinity was 11.7 and 24.3
      micrograms.hr/ml for fine granules, and 8.3 micrograms.hr/ml for capsules. The
      cumulative excretion rates up to 120 hours after the start of treatment were 8.24
      and 13.84% for fine granules, and 3.83% for capsules. AZM was administered to 123
      patients once daily at 3.7-20.0 mg/kg body weight over 3 to 5 days with reference
      to the standard dose of 10 mg/kg. The drug was used to treat patients with
      pharyngitis, tonsillitis, scarlet fever, pneumonia, mycoplasmal pneumonia,
      chlamydial pneumonia, otitis media, pertussis, intestinal infection, and SSTI.
      The effectiveness of AZM was evaluated in 109 cases. The drug was rated
      "excellent" in 65.1% of the patients and "good" in 29.4%, resulting in an
      efficacy rate of 94.5%. Furthermore, AZM eradicated 43 of 46 (93.5%) bacteria
      that had been identified before the treatment. Three patients complained of side
      effects of urticaria (1 case) and diarrhea (2 cases). Abnormal laboratory changes
      were reported as follows: decreased leukocyte (3 cases), increased eosinophil
      (5), increased platelet (2), increased eosinophil and platelet, elevated GPT (1),
      and elevated GOT and GPT (1). The abnormalities, however, were mild enough to
      raise no clinically significant problems. In conclusion, AZM in once daily
      regimen was effective and safe in treatment of pediatric infections.

PMID- 8986554
TI  - [Clinical evaluation of azithromycin in pediatric infections].
AB  - Azithromycin (AZM) was studied for its clinical efficacy in pediatric infections.
      The study on AZM was carried out in 43 patients whose diagnoses were given as
      follows: pharyngitis in five cases, tonsillitis in one, bronchitis in four,
      pneumonia in four, Mycoplasma pneumonia in 14, scarlet fever in nine, impetigo in
      four, pyodermia in one and Campylobacter enteritis in one. The patients received
      AZM once daily at 1.6 approximately 20.0 mg/kg body weight for three to five
      days. Effectiveness of AZM was evaluated in 39 cases and the drug was rated
      "excellent" in 15, "good" in 19, "fair" in one, "poor" in four, resulting in an
      efficacy rate of 87.2%. Twenty bacterial isolates were identified as causative
      isolates in 19 patients: Staphylococcus aureus, Streptococcus pyogenes,
      Streptococcus pneumoniae, Haemophilus influenzae, Campylobacter jejuni and
      Mycoplasma pneumoniae. AZM eradicated 16 isolates but four persisted after
      therapy. One patient complained of loose stool, while two patients were found
      with decreases in white blood cell counts, and seven showed increases in
      eosinophils. However, no serious case of adverse event was reported.

PMID- 8986555
TI  - [Therapeutic efficacy of azithromycin in pediatrics].
AB  - Azithromycin (AZM), a newly developed azalide antibiotic, was administered at a
      standard dose of 10 mg/kg once daily for 3 days to pediatric patients with
      bacterial infections and the therapeutic efficacy of AZM was investigated. 1. A
      total of 12 patients with the following diseases was evaluated: pharyngitis in
      two, tonsillitis in four, bronchitis in one, Mycoplasma pneumonia in one, scarlet
      fever in two and enteritis in two. The drug was rated "excellent" in eight cases
      and "good" in four. 2. Eleven strains were isolated from patients: five strains
      of Streptococcus pyogenes, four strains of Haemophilus influenzae, and two
      strains of Haemophilus parainfluenzae. Isolated bacteria were eradicated in eight
      strains and persisting in one, resulting in 88.9% in eradication rate. No follow
      up examinations in post-treatment were performed in two cases. 3. No adverse
      reaction was reported, while one case of eosinophilia was noted as an abnormal
      laboratory test value. 4. As far as compliance is concerned, patients claimed
      that the formulation of the drug is "easy to take" or "ordinary". With the
      results presented as above, we have concluded that AZM is a useful antibiotic in
      pediatric patients with bacterial infections.

PMID- 8986556
TI  - [Therapy with azithromycin in pediatric infections].
AB  - Azithromycin (AZM) was orally administered to 12 pediatric patients with the
      following bacterial infections: pharyngitis in four cases, tonsillitis in one,
      pharyngo-bronchitis in two, and mycoplasmal pneumonia in five. In eleven of the
      twelve cases (91.7%) was the drug found effective. Neither abnormal clinical
      findings nor abnormal laboratory test results changes were observed. Eleven of
      the twelve pediatric patients claimed that the formulation of the drug is easy to
      take. The above results suggest that AZM is a useful antibiotic drug in the
      treatment of pediatric patients with bacterial infections.

PMID- 8986557
TI  - [Clinical studies on azithromycin in pediatrics].
AB  - Fine granules or capsules of azithromycin (AZM) were given to 32 pediatric
      patients for the treatment of the following diseases: pharyngitis in three cases;
      tonsillitis in one; bronchitis in six; pneumonia in six; mycoplasmal pneumonia in
      14; pertussis and enteritis in one, each. Effectiveness of AZM was evaluated in
      30 cases and the drug was rated "excellent" in 18 patients, "good" in 11 and
      "fair" in one, resulting in a total efficacy rate of 96.7%. Three strains of
      bacteria were isolated from 3 patients as the causative organisms including:
      Streptococcus pneumoniae, Haemophilus influenzae and Haemophilus parainfluenzae,
      from three different patients, respectively. One patient complained of mild
      diarrhea, another patient mild urticaria. Abnormal laboratory test results were
      reported as follows: one patient showed a slight decrease in leukocyte count,
      three patients showed slight increases in eosinophils, and one patient had slight
      elevations in GOT and GPT. The above results suggest that AZM is a useful
      antibiotic drug in the treatment of pediatric patients with various bacterial
      infections.

PMID- 8986558
TI  - [Antimicrobial activity of cefodizime against clinical isolates].
AB  - In order to evaluate antimicrobial activity of cefodizime (CDZM), minimum
      inhibitory concentrations (MICs) of CDZM and control drugs were determined
      against clinical isolates collected from nation-wide medical institutions and in
      our laboratory from September to December of 1992 and from September to December
      of 1995. The results are summarized as follows: 1. Bacterial species with no or
      few strains resistant to CDZM included Streptococcus pyogenes, Haemophilus
      influenzae, Citrobacter koseri, Proteus mirabilis and Neisseria gonorrhoeae. The
      range of MIC values of CDZM against Klebsiella pneumoniae was spread. Other
      strains, Streptococcus pneumoniae, Moraxella subgenus Branhamella catarrhalis,
      Escherichia coli, Citrobacter freundii, Enterobacter spp., Serratia marcescens,
      Proteus vulgaris, Morganella morganii, Providencia spp., Peptostreptococcus spp.
      and Bacteroides fragilis group were resistant to cephems including CDZM. 2. The
      MIC90's of CDZM were 0.05 approximately 3.13 micrograms/ml against Streptococcus
      spp., H. influenzae, M. (B.) catarrhalis, E. coli, Klebsiella spp., P. mirabilis,
      N. gonorrhoeae and Peptostreptococcus spp. obtained in 1995 that were frequently
      found in daily treatment of infections. It appears that the effectiveness of CDZM
      was still relatively high against community-acquired infections. 3. Among H.
      influenzae isolates included imipenem (IPM)-resistant and norfloxacin (NFLX)
      resistant strains. The MIC-range of CDZM against strains collected in 1995
      including IPM-resistant and NFLX-resistant strains was < or = 0.025 approximately
      0.1 microgram/ml, and MIC90 against these strains was 0.05 microgram/ml. CDZM
      showed strong antimicrobial activities against H. influenzae strains resistant to
      carbapenems and new-quinolones.

PMID- 8986559
TI  - [Influence of multiple-dose administration of cefetamet pivoxil on blood and
      urinary concentrations of carnitine and effects of simultaneous administration of
      carnitine with cefetamet pivoxil].
AB  - Cefetamet pivoxil (CEMT-PI), a drug of pivaloyloxymethyl group, was investigated
      for its impact on the carnitine blood homeostasis and renal excretion upon
      administering CEMT-PI alone, and CEMT-PI simultaneously with carnitine. 500 mg of
      CEMT-PI (group A) and 500 mg of CEMT-PI and an equimolar amount (200 mg of
      carnitine) of levocarnitine chloride (group B) were administered twice a day for
      7 and 1/2 consecutive days to 5 healthy volunteers (group A) and 3 healthy
      volunteers (group B). No serious side effects nor abnormal values in physical and
      laboratory tests were observed throughout the study in both groups. During the
      treatment period, plasma total carnitine decreased slowly down to 25.5 microM
      (group A) and 38.8 microM (group B) and plasma free carnitine reached steady
      state levels at 17.7 microM (group A) and 29.2 microM (group B) on day 5. These
      concentrations represent 45 and 37% in group A, 66 and 58% in group B of the
      average pre-treatment baseline levels. Plasma pivaloylcarnitine quickly reached
      plateau levels of 6.12 microM (group A) and 4.05 microM (group B) on day 4. After
      treatment stop, plasma total and free carnitine returned to the pretreatment
      baseline level within 5 days (group A) and 3 days (group B), and plasma
      pivaloylcarnitine was detectable until day 7 of the treatment-free follow up in
      both groups. Although carnitine was given concurrently at a dose equimolar to the
      ingested amount of pivalic acid in group B, the plasma total and free carnitine
      exhibited a decrease. This was considered attributable to the fact that the
      bioavailability of carnitine is as low as 16% when administered orally, which is
      considerably less compared to the 55% bioavailability of cefetamet pivoxil.

PMID- 8986560
TI  - Consumer surveys of health plan performance: a comparison of content and approach
      and a look to the future.
AB  - BACKGROUND: Escalating demand in the market-place for consumer-supplied data on
      health plan performance has led to a growing number of competing survey
      instruments. Many of them offer distinct perspectives on what concepts should be
      measured and how they should be measured. The principal user groups of this
      information-purchasers, consumers, and health plans-face an increasingly complex
      decision when choosing between instruments. DIALECTIC OF SURVEY DEVELOPMENT: Many
      of the differences between surveys arise because the three user groups apply
      survey results for different purposes. At the same time, a standardized
      instrument would provide the three user groups more information and context. A
      dialectic process between these two dynamics is guiding the exchange between
      survey developers and users and is resulting in slow if somewhat unsteady
      progress toward consensus on common core content across user groups. SIX CONSUMER
      SURVEYS: This article seeks to promote public debate on the content and approach
      of consumer surveys of plan performance, a task that is separate from comparative
      empirical testing. Six instruments are described-the Consumer Satisfaction
      Survey, Employee Health Care Value Survey, Health Plan Value Check, Adult Health
      Care Survey, Annual Member Health Care Survey-Version 1.0, and the Consumer
      Health Plan Value Survey. To help differentiate the instruments, several common
      methodologic choice points faced by each (for example, use of "not applicable" as
      an option) are highlighted. The alternative approaches taken by the instruments
      to address these choice points are discussed in terms of the arguments for and
      against their use. ANTICIPATING THE FUTURE: Although it is too early to predict
      which survey measures or approaches will figure most heavily in the eventual core
      instrument, it is not too early to anticipate that the critical decisions will be
      made on both academic (for example, psychometric and cognitive testing) and
      marketplace criteria. Increasingly influential will be collective user
      prerequisites emerging out of the interplay of the three user groups in the
      marketplace. Six key collective prerequisites (for example, defining common
      ground between the user groups) are identified, and their likely impact on the
      development of consumer surveys of health plan performance are described.

PMID- 8986561
TI  - Collaboration between a referring hospital and a tertiary care center in
      improving the transfer process for cardiac patients.
AB  - BACKGROUND: Transfer of cardiac patients between hospitals is a complex process
      with many implications for quality of care. In the case of heart disease,
      specialized procedures such as coronary angioplasty, coronary bypass surgery, and
      valve replacement or repair require the performance of cardiac catheterization
      and coronary arteriography in a catheterization laboratory, as well as the
      availability of cardiac surgical services. The Department of Veterans Affairs
      Medical Center (DVAMC) at Muskogee, Oklahoma, transfers most cardiac patients
      requiring specialized diagnostic procedures and advanced cardiac care to DVAMC at
      Oklahoma City, Oklahoma. Concerns about the inefficiency of the transfer process
      led to the launch of a quality improvement project in late 1992. CHANGES IN THE
      TRANSFER PROCESS: Greater emphasis was placed on medical aspects compared to
      administrative aspects of transfer, and ready access to the physicians at DVAMC
      at Oklahoma City was provided. RESULTS: The time from request for transfer to the
      actual transfer decreased. Before the quality improvement project, only 33% of
      transfers of cardiac patients were completed within 24 hours-versus 78% in 1993
      and 1994, 89% in 1995, and 84% in the first half of 1996. In addition, DVAMC
      Muskogee physician satisfaction regarding services at DVAMC-Oklahoma City
      improved. CONCLUSION: Ongoing discussion between the cardiology team at the
      accepting hospital and physicians at the referring hospital expanded the
      continuum of care to both hospitals. Priority of transfers could be upgraded at
      any time without unduly jeopardizing patient safety or increasing resource
      utilization at the receiving center.

PMID- 8986562
TI  - A quality improvement team on autologous and directed-donor blood availability.
AB  - BACKGROUND: Until 1985, volunteer donors provided blood for almost all
      transfusions and donated blood was rarely restricted for transfusion to a
      specific patient. With the AIDS (Acquired Immunodeficiency Syndrome) crisis,
      autologous (blood from oneself) and directed (blood from families and friends)
      donations increased, calling for handling of far greater complexity. At the
      University of California at San Francisco Medical Center, the demand for special
      donations superseded the development of systems to meet the demand and autologous
      and/or directed donations were often not available when needed. After a rapid
      rise in incident reports and complaints from physicians, nurses, patients, and
      families, a quality improvement (QI) team was formed in mid-1991 to improve blood
      availability. METHOD: Meetings were held to analyze the processes involved in
      blood donation and transfusion, identify and categorize problems, develop
      interventions, test and implement solutions, and monitor improvements.
      Educational efforts were implemented throughout the medical center, recruitment
      for a special donations co-ordinator began, and changes were made in the blood
      bank's internal systems. RESULTS: In two years, with stable numbers of transfused
      units, the number of incident reports regarding blood availability decreased from
      19 to 2 per year-an improvement that has been sustained for more than three
      years. The QI team continues to meet regularly to design and implement additional
      improvements. CONCLUSION: A QI team has improved the availability of autologous
      and directed-donor blood to patients and has extended the impact of the QI
      methodology throughout the medical center as a whole.

PMID- 8986563
TI  - Measuring seriousness of hospital quality of care issues.
AB  - BACKGROUND: A 1995 article showed that the discipline of the person who
      determines what constitutes a serious quality of care issue is significantly
      associated with the type of issues identified as serious. Moreover, what is a
      serious issue for one organization or provider may be a minor issue for another.
      METHODS: Six hundred hospital administrators, physicians, nurses, and quality
      managers in 72 hospitals rated the seriousness of issues they had identified in
      their own hospitals. A panel of 90 external hospital administrators, physicians,
      and quality managers rated a condensed set of the same issues. RESULTS: Across
      all the hospitals, internal scores were significantly lower (less serious) than
      external scores. Internal respondents consistently rated issues identified in
      their hospital lower than did external raters. The mean internal rating was .60
      times the score for the anchor issue ("late lab or x-ray results," assigned a
      score of 300), while the mean external rating was 1.73 times the anchor score.
      DISCUSSION: Convergence of internal and external perceptions of the seriousness
      of quality of care issues in hospitals cannot be assumed. This raises questions
      about the effects of applying external judgments on seriousness of quality of
      care issues, such as those used in report cards or other external reports on
      hospital quality of care. CONCLUSION: There is greater conformity of viewpoint
      when respondents are asked to adopt an industrywide perspective rather than an
      internal one. External raters are more likely to consider problems serious than
      are internal raters, possibly because they do not have local knowledge of
      mitigating circumstances.

PMID- 8986564
TI  - Bladder management after total joint arthroplasty.
AB  - This study was undertaken to determine the impact of an indwelling Foley catheter
      on bladder dysfunction and incidence of urinary tract infections after total
      joint arthroplasty. A prospective randomized controlled trial was conducted
      assigning use of an indwelling Foley catheter (group 1) or intermittent
      catheterization (group 2) for 48 hours following operation. Postoperative
      cultures were obtained on days 2 and 5, and the number of intermittent
      catheterization events and void and catheterization volumes were recorded.
      Concurrent cost-effectiveness analysis was conducted. One hundred nineteen of 174
      consecutive patients having elective primary total joint arthroplasty completed
      the study. Five of 62 patients (8%) in group 1 and 7 of 57 patients (12%) in
      group 2 developed urinary tract infections (NS, P = 45). Twenty patients (35%) in
      group 2 and 12 (19%) in group 1 required straight catheterization for inability
      to void 48 hours after surgery (P = .05). Seventeen patients (35%) in group 2 and
      eight patients (16%) in group 1 required straight catheterization after epidural
      analgesia was discontinued (P = .024). Bladder management by indwelling Foley
      catheter saved more than 150 minutes of direct nursing contact per patient and
      $3,000 in total hospital costs. Indwelling Foley catheters reduced the frequency
      of postoperative urinary retention, were less labor intensive than intermittent
      straight catheterization, and were not associated with an increased risk of
      urinary infection. In the setting of epidural anesthesia and postoperative
      analgesia for total joint arthroplasty, management by indwelling catheter is a
      cost-effective strategy to facilitate postoperative return of normal bladder
      function.

PMID- 8986565
TI  - Total joint arthroplasty in orthotopic liver transplant recipients.
AB  - Eight total hip and two total knee arthroplasties were performed from 1986 to
      1991 in eight patients who had orthotopic liver transplantation. The indications
      for joint arthroplasty were avascular necrosis of the femoral head in five hips,
      pathologic femoral neck fracture caused by osteopenia in three hips, avascular
      necrosis of femoral and tibial condyles in one knee, and posttraumatic arthritis
      in one knee. Six patients (75%) had significant osteopenia. The mean interval
      between liver transplantation surgery and hip or knee joint arthroplasty was 2
      years (8-48 months). The patients who had hip arthroplasty were followed for a
      mean of 4.85 years (2-8 years), and those who had a knee arthroplasty after a hip
      arthroplasty, for a mean of 3.5 years (2-5 years) after the knee arthroplasty. In
      the patients who had hip arthroplasty, the mean Harris hip score was improved
      from 34 to 82 points. In the two patients who had a knee arthroplasty, the mean
      score was improved to 100 points both for pain and function of the knee and for
      overall function from mean preoperative knee scores of 49 and 25 points,
      respectively. Radiographs did not reveal any loosening of the components. None of
      the patients required reoperation and there were no serious postoperative
      complications.

PMID- 8986566
TI  - Neglected congenital dislocation of the hip. Role of computed tomography and
      computer-aided design for total hip arthroplasty.
AB  - Computed tomography (CT) provides important three-dimensional anatomic details in
      congenital dislocation of the hip that are useful for total hip arthroplasty
      (THR) and are not obtainable with conventional radiographic evaluation. In this
      study, 84 patients (119 hips) with congenital dislocation of the hip were
      evaluated with CT before surgery. Specifically, both the acetabulum and the femur
      were analyzed to make the best selection of the prosthesis. The average
      anteversion of the acetabulum was 23 degrees, with an opening of 30.9 mm and a
      depth of 14.7 mm. The bone stock of the true acetabulum was calculated and the
      average available diameter for the acetabular implant was 44.9 mm. The CT
      topogram revealed the true leg-length discrepancy (average 0.5-1.9 cm), and the
      amount of a shortening osteotomy when necessary was determined. Finally, to
      determine the stem with optimum fit and fill, a three-dimensional reconstruction
      of the femoral canal using CT data and computer-aided design (CAD) was matched
      with a three-dimensional geometry of several stem designs and sizes obtained from
      a CAD system.

PMID- 8986567
TI  - Total knee arthroplasty in patients with parkinson's disease.
AB  - A retrospective review of 24 consecutive patients with Parkinson's disease who
      underwent 33 primary cemented condylar total knee arthroplasties was performed.
      The average follow-up period was 33 months, with a minimum follow-up period of 2
      years. The pain score improved from 34 points before surgery to 89 points at the
      latest follow-up examination. The functional score improved from 42 points before
      surgery to 68 points at the latest follow-up examination. In patients whose
      Parkinson's disease progressed, the latest functional score was 49.5 points,
      significantly lower than the scores of those patients who did not progress. The
      results show that total knee arthroplasty is successful in patients with
      Parkinson's disease. Unfortunately in some patients. Parkinson's disease
      progresses and functional results decrease, but the benefit of pain relief
      persists.

PMID- 8986568
TI  - Custom total hip arthroplasty.
AB  - Custom total hip arthroplasty (THA) has been advocated as a primary operation to
      achieve optimal proximal fit and fill in THA. Because of the increased cost of
      the implant, it must be proved that survivorship of the custom component is
      improved compared with a well-cemented or cementless off-the-shelf femoral
      prosthesis. A series of 64 primary and revision femoral component custom titanium
      uncemented THAs were reviewed. In the primary custom group 90.9%, and in the
      revision group 80%, had good to excellent results using the Harris hip scoring
      system at a mean follow-up period of 6.5 years. The age range was 32 to 74 years
      (mean, 53 years). Thigh pain was present in 17% of the patients in this series.
      Significant osteolysis occurred in 4.7% of the cases. The average time to failure
      for the four primary custom THAs was 4.1 years, and for the four revision custom
      THAs, 2.4 years. Despite excellent proximal fit and fill, these short-term
      results have not resulted in improved success rates compared with a well-cemented
      or cementless off-the-shelf femoral component when performing THA.

PMID- 8986569
TI  - Clinical and radiographic results of the Total Condylar III and Constrained
      Condylar total knee arthroplasty.
AB  - The Total Condylar III (Johnson and Johnson, Braintree, MA) and Constrained
      Condylar (Zimmer, Warsaw, IN) knee prostheses are nonlinked, semi-constrained
      prosthetic alternatives to rigid or rotating hinge prostheses for use in complex
      knee reconstructions. Forty-six Total Condylar III or Constrained Condylar
      prostheses were implanted with cement in 36 patients and followed for a mean of 5
      years (range, 2-9 years). There were 25 primary total knee arthroplasties and 21
      revision total knee arthroplasties. The knees were evaluated using The Hospital
      for Special Surgery 100-point knee rating system. Overall, 40 knees (87%) had a
      good or excellent clinical result, 2 knees (4%) had a fair result, and 4 knees
      (9%) had a poor result. There was one revision for loosening of a cemented,
      nonmodular Constrained Condylar prosthesis, and one knee had a debridement for a
      late, metastatic infection, but the components were retained. There were no
      mechanical failures in those knees that were primary arthroplasties, but two
      mechanical failures occurred in those knees that were revision arthroplasties.
      Radiographic review showed one asymptomatic loosening of a Constrained Condylar
      tibial component with an uncemented press-fit stem, and only 8 knees had
      scattered nonprogressive tibial bone-cement radiolucent lines. The Total Condylar
      III and Constrained Condylar semiconstrained prostheses are successful when used
      in complex knee reconstructions.

PMID- 8986570
TI  - Results of total knee arthroplasty with a metal-backed patellar component. A 6
      year follow-up study.
AB  - This study reviews the clinical outcome of knee arthroplasty (Microloc, Johnson &
      Johnson Orthopedics, Norderstedt, Germany) with a resurfacing metal-backed
      patellar component. Thirty patients were available for clinical and radiographic
      reexamination with follow-up periods of 36 and 72 months. There were 21 women and
      9 men, with an average age of 71.1 years. At the follow-up examination, seven
      patients demonstrated a metallic friction noise, and three had only mild
      crepitation at the patellofemoral joint level. In the group complaining of knee
      pain, the average knee score dropped from 76.9 +/- 9.9 at 36 months to 44.7 +/-
      15.3 (P < .05) prior to revision surgery on average at 66 months. The function
      score dropped during the same time from 72.0 +/- 19.7 to 53.5 +/- 14.9. In
      contrast, the pain-free group did not demonstrate any significant changes in
      either knee or function score. Radiographic evaluation showed a patellar tilt of
      8.1 degrees +/- 4.0 degrees in the group complaining of pain, compared with 2.5
      degrees +/- 2.3 degrees in the pain-free patient collective. All 10 patients
      complaining of pain and increasing disability underwent revision surgery. At the
      time of surgery, an obvious polyethylene particle-induced synovitis was found,
      and in 7 patients it was associated with a metallosis. One of the main reasons
      for failure of metal-backed polyethylene components is thought to be the undue
      high stresses forced onto the insert. High loading of only a small fraction of
      the surface will lead to increased polyethylene creep and particle formation,
      resulting in synovitis and finally metallosis. Early revision seems to be the
      best solution to prevent progressive destruction of the entire joint. Previously
      reported results on metal-backed patellar components show a failure rate of 8.4%
      after 12 to 24 months. In this study, this rate had already increased to 33.3%
      after 6 years. One might therefore speculate that at 10 years, revision surgery
      might become necessary in more than 50% of the surviving patients with this type
      of implant.

PMID- 8986571
TI  - Results of different surgical procedures on total knee arthroplasty infections.
AB  - Seventy-six consecutive infected total knee arthroplasties in 74 patients were
      treated between December 1981 and March 1990. The average follow-up period was 57
      months (range, 24-121 months). No patients were lost to follow-up evaluation and
      12 patients died from unrelated causes. Patients were classified, based on the
      duration of their symptoms prior to treatment, as acutely infected (< 2 weeks) or
      chronically infected (> 2 weeks). All knees were evaluated following surgical
      treatment with radiographs and Knee Society knee score assessment. Successful
      eradication of infection was defined as a knee without clinical evidence of
      infection for a minimum of 2 years. The initial treatment modality was successful
      in eliminating the infection in 69 of 76 patients (90%). Infection was eventually
      eradicated in 72 of 76 (94%) patients. The individual clinical result was found
      to be more dependent on a patient's medical and musculoskeletal status (patient
      class A, B, C) than on knee score or radiographic assessment. Careful treatment
      selection based on patient class and duration of infection can result in a
      predictable and successful result.

PMID- 8986572
TI  - Elution characteristics of vancomycin and tobramycin combined in acrylic bone
      cement.
AB  - Combining two antibiotics in antibiotic-loaded bone-cement is common in clinical
      practice. As the effect this has on elution characteristics is unknown, an in
      vitro quantitative elution study was carried out. Three groups of five antibiotic
      loaded cement disks were prepared and placed in individual saline baths for 5
      weeks. The elution of tobramycin from the disks in the study group (containing
      2.4 g tobramycin and 1.0 g vancomycin per 40-g packet of Palacos-R cement powder
      [Smith & Nephew Orthopaedics, Memphis, TN]) was increased by 68% over that of the
      tobramycin control disks (2.4 g tobramycin only) (P = .024). The release of
      vancomycin from the study group disks was increased by 103% over the vancomycin
      control disks (1.0 g vancomycin only) (P = .007). Combining two antibiotics in
      bone-cement improves elution of both antibiotics in vitro and may translate into
      enhanced elution in vivo.

PMID- 8986573
TI  - Differences in stiffness of the interface between a cementless porous implant and
      cancellous bone in vivo in dogs due to varying amounts of implant motion.
AB  - To determine the mechanical properties of the interface between the tissue
      ingrowth into porous coatings and the implant, porous-coated cylindrical implants
      were inserted into the distal femur in 20 mature dogs and oscillated in vivo 8
      hours per day for 6 weeks at fixed amounts of micromotion (0, 20, 40 and 150
      microns). Applied torques and resulting displacements were recorded. The
      torsional resistance per unit angular displacement (TR/AD), reflecting the
      stiffness of the bone-porous coating interface, was 0.88 +/- 0.25 N-M/deg
      immediately after implantation in the 20-micron displacement group. It increased
      with time after surgery, reaching a maximum of 1.25 +/- 0.60 N-M/deg at 6 weeks.
      The TR/AD was lower initially (0.77 +/- 0.43 N-M/deg) in the 40-micron group and
      gradually decreased with time after surgery, reaching a maximum of 0.54 +/- 0.13
      N-M/deg at 6 weeks. The TR/AD was even lower (0.24 +/- 0.10 N-M/deg) in the 150
      micron group initially and remained the same (0.16 +/- 0.09 N-M/deg) with time
      after surgery. Histologic evaluation showed bone ingrowth in continuity with the
      surrounding bone in the 20-micron group consistent with the high stiffness values
      at sacrifice. In contrast, a mixture of fibrocallus and bone were found at the
      bone-porous coating interface in the 40-micron group, consistent with the
      intermediate stiffness values. In contrast, despite the fact that bone was found
      in the depth of the porous coating in the dogs in the 150-micron group, the low
      stiffness values were a reflection of fibrous tissue formation at the interface
      in that group, because of the large motion disrupting bony ingrowth at the bone
      porous coating interface. By monitoring the torsional resistance per unit of
      angular displacement dynamically in vivo, it was possible to evaluate the
      mechanical properties of the bone-porous coating interface as tissue ingrowth
      proceeded. Twenty microns of oscillating displacement was compatible with stable
      bone ingrowth with high interface stiffness, whereas 40 and 150 microns of motion
      was not.

PMID- 8986574
TI  - Average and peak contact stress distribution evaluation of total knee
      arthroplasties.
AB  - Seven total knee arthroplasty systems were tested to determine contact stress
      patterns and contact areas using a calibrated Fuji film stress analysis
      technique. Knees were loaded to 2,000 N (204 kg) at 15 degrees, 60 degrees, 90
      degrees, and 135 degrees flexion at 24 and 37 degrees C. Evaluation of stresses
      at 37 degrees C at 15 degrees and 60 degrees using an average contact stress
      assessment technique indicated that the LCS meniscal bearing knee system, (DePuy,
      Warsaw, IN), the AMK knee with a constrained insert (DePuy), and the PFC knee
      with a posterior-lipped insert (Johnson and Johnson, Raynham, MA) had the lowest
      average contact stresses (near or below 10 MPa). The PFC with a regular insert
      (Johnson and Johnson) the Ortholoc II (Dow Corning Wright, Arlington, TN), and
      the AMK with a regular insert (DePuy) had intermediate contact stresses. The AMK
      with a Hylamer-M insert (DePuy) and the MG II (Zimmer, Warsaw, IN) had the
      highest average contact stresses (near or above 20 MPa). A stress-calibrated Fuji
      film measurement technique has shown that an assessment of ranges of contact
      stress provides much more information about regions of expected wear than an
      assessment of average contact stresses. Testing of the tibiofemoral articulation
      of artificial knees revealed that all knees had some areas of contact with
      maximum stresses in excess of 15 MPa. As the yield strength of ultrahigh
      molecular-weight polyethylene is approximately 15 MPa, all tibial inserts could
      wear to some extent. Peak contact stresses at four test angles of the AMK, Series
      7000 (Osteonics, Allendale, NJ:) Genesis (Smith & Nephew Orthopaedics, Memphis,
      TN), and MG II patellofemoral articulations were high (above 30 MPa). Contact
      areas varied from line-shaped to bilateral circular or elliptical shapes. The LCS
      knee system experienced substantially lower patellofemoral contact stresses and
      larger contact areas. Changes in conformity of knee designs are warranted to
      overcome wear problems. Peak contact stresses measured from the LCS meniscal
      bearing tibiofemoral and patellofemoral joint were in excess of 30 MPa in some
      areas at low flexion angles. This design does create large areas of contact at
      very low contact pressures, however, and for this reason is expected to wear less
      than other designs.

PMID- 8986575
TI  - Extended tibial tubercle osteotomy in total knee arthroplasty.
AB  - Thirty tibial tubercle osteotomies were performed to obtain exposure and
      facilitate patellar tracking in 29 patients who underwent total knee
      arthroplasty. The thickness and width of the bone fragment were gradually tapered
      from proximal to distal. Fixation was obtained with three or four titanium
      screws. Average follow-up period was 18 months. Twenty-nine of the osteotomies
      healed primarily. In one patient, postoperative displacement of the tibial
      tubercle developed requiring additional screw and suture fixation. Extended
      tibial tubercle osteotomy is a useful technique during difficult total knee
      arthroplasty. Poor tibial bone stock is a relative contraindication. The authors
      recommend that a long tapered bone fragment that is 1.5 to 2 cm thick at the
      level of the tibial tubercle be elevated and fixation achieved with screws.

PMID- 8986576
TI  - Implant matching can improve joint implant selection.

PMID- 8986577
TI  - Implant matching has no clinical or scientific basis.

PMID- 8986578
TI  - Early delamination of a Hylamer-M tibial insert.

PMID- 8986579
TI  - Recurrent hemarthrosis after total knee arthroplasty.
AB  - Seven patients developed recurrent hemarthroses following total knee
      arthroplasty. The average interval between arthroplasty and the first bleed was
      more than 20 months (range, 1-30 months). All seven required open synovectomy an
      average of 21 months (6-31 months) after arthroplasty. Follow-up evaluation
      averaged 44 months (19-60 months) and all had an excellent result without further
      bleeds. A prolific synovitis was seen in all cases, with histologic features
      revealing a chronic synovitis with fibrosis and hemosiderin staining. Entrapment
      of the proliferative synovial tissue between the components is postulated to be
      the etiology for these recurrent bleeds which averaged four per patient prior to
      synovectomy.

PMID- 8986580
TI  - Prosthesis displacement as a complication of reduction of a dislocated total hip
      arthroplasty.
AB  - Acute displacement at the cement-prosthesis interface of the femoral component of
      a hip arthroplasty that occurred as a consequence of attempted reduction of a
      dislocation is described. Although this complication is theoretically possible
      with a polished tapered stem design, it is previously unrecognized, and may be
      avoidable if fluoroscopic control is used during closed reduction of a
      dislocation.

PMID- 8986581
TI  - Treatment of periprosthetic fractures around total hip arthroplasty with an
      extensively coated femoral component.
AB  - Late periprosthetic fractures may occur around loose cemented femoral components,
      usually as a consequence of osteolytic bone deficiency. The management of these
      fractures should include revision total hip arthroplasty using techniques that
      achieve fracture healing and component stability. If a cementless component is to
      be used, osseointegration is desirable. Presented herein is a technique of
      revision total hip arthroplasty for this injury using a curved, extensively
      coated femoral component. Four cases have been followed for a minimum of 2 years.
      Each case achieved a good or excellent clinical outcome while radiographs
      demonstrated fracture healing and osseointegration.

PMID- 8986582
TI  - Acute meniscal injury following successful unicompartmental knee arthroplasty.
AB  - The case of an active 53-year-old man with a well-functioning unicompartmental
      knee arthroplasty who suffered an acute athletic injury to the knee is described.
      A mechanical problem was diagnosed and he was successfully treated by
      arthroscopic partial lateral meniscectomy for a displaced meniscal tear. This
      case points to an important difference noted by history and physical examination
      between an acute injury to the unreplaced compartment of a knee with a
      unicompartmental knee arthroplasty and progression of the arthritic process.

PMID- 8986583
TI  - Fertility drugs and ovarian epithelial cancer: is there a link?

PMID- 8986584
TI  - Cryopreservation of embryos: medical, ethical, and legal issues.

PMID- 8986586
TI  - Fertilization and pregnancy using metaphase I oocytes in an intracytoplasmic
      sperm injection program.
AB  - PURPOSE: In this study we investigated whether metaphase I oocytes collected in
      an intracytoplasmic sperm injection program could successfully be matured and
      fertilized by injecting aged (> 20-hr) spermatozoa. MATERIALS AND METHODS:
      Metaphase I oocytes aspirated were preincubated for 20 hr to allow the oocytes to
      reach meiotic maturity. Only metaphase II oocytes were injected. The original
      sperm sample processed on the day of aspiration was used in the microinjection
      process. RESULTS: One hundred eighty-three oocytes were collected, of which 42
      (23%) were metaphase I oocytes. These were incubated for 20 hr and microinjected
      with the original sperm sample. Thirty-one (74%) of the metaphase I oocytes
      reached meiotic maturity (extruded polar body): 67.7% showed two pronuclei 18 hr
      after injection and 61.3% embryo development 40 hr postinjection. No difference
      in fertilization and embryo development rate was found in metaphase II oocytes
      injected 6 hr postaspiration versus 20 hr postaspiration. An ongoing pregnancy
      was also achieved using only embryos obtained from matured metaphase I oocytes.
      CONCLUSIONS: Metaphase I oocytes can be successfully matured in vitro and
      injected using aged (> 20-hr) sperm samples. Matured metaphase I oocytes, if
      successfully injected, produce embryos able to induce pregnancy.

PMID- 8986585
TI  - Coculture with homologous oviductal cells improved the implantation of human
      embryos--a prospective randomized control trial.
AB  - PURPOSE: The efficacy of homologous oviductal cell coculture on the success of a
      human in vitro fertilization program was investigated in a prospective randomized
      control clinical trial. METHODS AND RESULTS: One hundred eighty-one couples were
      randomized into the control and the coculture groups. Pronuclear-stage zygotes
      were either cultured in Earles' balanced salt solution supplemented with 15%
      preovulatory serum (control) or cultured with human oviductal cells (coculture)
      for 24 hr before embryo transfer. There was no difference in the age of the
      patients, indication for treatment, number of oocyte retrieved or fertilized, or
      number of embryo replaced between the two groups. The pregnancy rates per
      transfer for the control and the coculture group were 12.8 and 19.3%,
      respectively. The number of viable fetus was significantly higher (P < 0.01, chi
      square test) in the coculture group (25/264) than in the control group (8/262).
      The coculture group also showed a higher multiple pregnancy rate, lower abortion
      rate, and more spare embryos suitable for cryopreservation.

PMID- 8986587
TI  - The production of interleukin-1 alpha immunoreactivity by human oviductal cells
      in a coculture system.
AB  - PURPOSE: The aim of this study was to determine the concentration of interleukin
      1 alpha in human embryo culture medium with or without oviductal cell coculture
      and to correlate the interleukin-1 alpha levels with pregnancy. METHODS: Culture
      media from 32 in vitro fertilization and embryo transfer cycles were assayed for
      interleukin-1 alpha by immunoassay technique. Human embryos were cultured in
      Earles' balanced salt solution supplemented with 15% preovulatory serum (sEBSS)
      in 16 of these cycles, while embryos in the rest of the cycles were cocultured
      with human oviductal cells in sEBSS. RESULTS: Both sEBSS and spent sEBSS after
      embryo culture contained low or undetectable levels of interleukin-1 alpha in the
      pregnant and nonpregnant cycles. On the other hand, oviductal cells significantly
      increased the amount of interleukin-1 alpha immunoreactivity in the conventional
      culture medium or coculture medium (P < 0.001, Mann-Whitney rank sum test). The
      concentrations of interleukin-1 alpha in the spent sEBSS after oviductal cell
      culture and after coculture with human embryos were 1.5 +/- 1.0 and 1.3 +/- 0.9
      pg/ml, respectively. There was no difference in the interleukin-1 alpha
      concentration between the pregnant and the nonpregnant coculture cycles.
      CONCLUSIONS: These data showed that human oviductal cells produced interleukin-1
      alpha immunoreactivity in a coculture system. However, this production could not
      be used as a marker for successful embryo implantation.

PMID- 8986588
TI  - Successful glucocorticoid treatment for patients with abnormal autoimmunity on in
      vitro fertilization and embryo transfer.
AB  - PURPOSE: To analyze the effects of glucocorticoid treatment for patients with
      abnormal autoimmunity on IVF-ET outcomes, low-dose predonisolone or dexamethasone
      was administered in 51 IVF-ET cycles of 41 patients with positive antinuclear
      antibody (ANA), anti-DNA antibody, and/or lupus anticoagulant (LAC). Rates of
      clinical pregnancy and implantation in these patients were compared with those in
      48 cycles without corticosteroid therapy. Autoantibody-negative patients were
      also treated with IVF-ET combined with (29 cycles) or without (57 cycles)
      glucocorticoid administration, and the pregnancy and implantation rates were
      investigated. RESULTS: Without glucocorticoid treatment, the pregnancy rate per
      cycle and implantation rate per embryo in antibody-positive patients were 10.4
      and 3.8%, respectively. Significant increases in pregnancy (35.3%) and
      implantation (13.2%) rates were observed with corticosteroid treatment. In
      antibody-negative patients, the rates of pregnancy and implantation showed no
      significant differences with versus without the glucocorticoid administration.
      CONCLUSIONS: Our results indicate that because autoimmune abnormalities may be at
      least one cause of implantation failure following IVF-ET, the combined use of low
      dose corticosteroid can be effective for autoantibody-positive women.

PMID- 8986589
TI  - Success rates following intracytoplasmic sperm injection are improved by using
      ZIFT vs IVF for embryo transfer.
AB  - PURPOSE: The purpose of this study was to analyze whether the mode of embryo
      transfer (ZIFT vs IVF) affected the outcome in intracytoplasmic sperm injection
      (ICSI) cycles. METHODS AND RESULTS: Eighty-two ICSI cycles (42 ZIFT and 40 IVF)
      were analyzed. Several variables, including patient age and weight, numbers of
      mature eggs collected, injected, and fertilized, fertilization rate, number of
      fertilized eggs obtained per cycle, numbers of zygotes/embryos transferred,
      clinical pregnancy rate, and implantation rate, were compared. Mean patient age
      and weight were identical. The mean number of mature eggs collected and injected
      and fertilization rate were significantly higher in the ZIFT group, however, the
      mean numbers of zygotes/embryos transferred were identical. The clinical
      pregnancy and implantation rates in ZIFT cycles (52.3 and 23.2% respectively)
      were significantly higher than in IVF cycles (17.5 and 9.7%). CONCLUSIONS: These
      data suggest that ZIFT is the more appropriate method for transfer of ICSI
      derived embryos.

PMID- 8986590
TI  - The in vitro development of mouse embryos beyond the blastocyst stage into the
      hatching and outgrowth stage using different energy sources.
AB  - PURPOSE: The purpose of this study was to investigate the effect of male and
      female serum supplementation on the in vitro development of mouse embryos beyond
      the blastocyst stage until the outgrowth stage since the latter may be related to
      the nidation of the embryo. We also studied the effect of EGF addition on embryo
      culture and blastocyst outgrowth. METHODS AND RESULTS: The blastocyst and
      hatching rates of two-cell mouse embryos cultured in Ham's F-10 + BSA, Ham's F-10
      + male serum, or Ham's F-10 + female serum were found to be comparable (P >
      0.05). The outgrowth rate of hatched blastocysts was significantly increased,
      though, when they were transferred to 50% male serum compared to either 50% BSA
      or 50% female serum (P < 0.01 and P < 0.05, respectively). In the last
      experiment, either 100 or 150 ng/ml EGF was added to the culture medium from the
      two-cell stage till blastocyst development and the latter were cultured till
      outgrowth in 50% BSA, male serum, or female serum. For both concentrations of
      EGF, the outgrowth rate was significantly higher in male serum compared to the
      other conditions (P < 0.01 and P < 0.05, respectively). The outgrowth rate was
      also higher when EGF was used compared to plain medium before transferring the
      blastocysts to either male or female serum (P < 0.01 for both). CONCLUSIONS: We
      conclude that the development of embryos to the outgrowth stage is significantly
      enhanced by male serum. The addition of EGF from the two-cell stage also
      significantly improves the outgrowth success rate for both male and female serum
      conditions.

PMID- 8986591
TI  - Efficacy of calcium ionophore A23187 oocyte activation for generating parthenotes
      for human embryo research.
AB  - PURPOSE: Our purpose was to examine the efficacy of Ca-A23187 to activate human
      oocytes and produce parthenotes for research purposes. We examined the
      feasibility of using fluorescence in situ hybridization (FISH) to study the sex
      chromosome constitution of activated oocytes. METHODS: One hundred eight
      nonfertilized oocytes from our IVF program were exposed to Ca-A23187. Oocyte
      activation was determined by the presence of pronuclear (PN) development. FISH
      was done on chromosome preparations using X and Y dual-colored probes.
      Polyploidic and parthenogenetically activated oocytes from our IVF program served
      as controls. RESULTS: Of the 108 oocytes, 59 (55%) had no PN, 38 (35%) one PN, 10
      (9%) two PN, and 1 (0.9%) three PN. Fiftyseven oocytes (53%) were not recovered
      following spreading and no chromatin was observed on 14 slides (13%) after FISH.
      This contrasted with 50 of 227 (22%) and 3 of 227 (1.7%) loss rates,
      respectively, for controls (P < 0.0001). Eight of 49 activated oocytes underwent
      cleavage. FISH was performed on 37 oocytes. Of 21 zero-PN oocytes, I had no FISH
      signals, 15 had a single X, 4 had two X's, and I had four X's. For one-PN
      oocytes, two had no FISH signals, seven had one X, and three had two X's. For two
      PN oocytes, two had no FISH signals and two had two X's. FISH results were
      consistent with a maternal origin of genetic material. CONCLUSIONS: Ca-A23187
      resulted in a 45% activation rate, with 16% of oocytes progressing to cleavage
      before degeneration. Oocyte activation with Ca-A23187 allowed the generation of
      parthenotes for human embryo research. FISH was useful for evaluation of oocytes
      and parthenotes.

PMID- 8986592
TI  - Normal twins born following preimplantation genetic diagnosis in a couple
      affected by X-linked hydrocephaly.

PMID- 8986593
TI  - The topology of transcription by immobilized polymerases.
AB  - Current models for RNA synthesis involve an RNA polymerase that tracks along a
      static template. However, research on chromatin loops suggests that the template
      slides past a polymerase immobilized in a large transcription factory. The
      evidence for immobilized polymerases is reviewed, and a model for transcription
      by such fixed enzymes is presented. According to the model, gene activation would
      involve reducing gene-factory distance and increasing the affinity of a promoter
      for a factory. Locus controlling regions and enhancers would attach to a factory
      and increase the chances that a promoter could bind to a polymerase; after
      transcriptional termination, the gene would detach from the factory. As some RNA
      processing occurs cotranscriptionally, processing sites are also likely to be
      associated with the factory.

PMID- 8986594
TI  - Dynamic changes in nuclear architecture during mitosis: on the role of protein
      phosphorylation in spindle assembly and chromosome segregation.
AB  - During mitosis, the vertebrate cell nucleus undergoes profound changes in
      architecture. At the onset of mitosis, the nuclear envelope breaks down, the
      nuclear lamina is depolymerized, and interphase chromatin is condensed to
      chromosomes. Concomitantly, cytoplasmic microtubules are reorganized into a
      mitotic spindle apparatus, a highly dynamic structure required for the
      segregation of sister chromatids. Many of the above events are controlled by
      reversible phosphorylation. Hence, our laboratory is interested in characterizing
      the kinases involved in promoting progression through mitosis and in identifying
      their relevant substrates. Prominent among the kinases responsible for regulating
      entry into mitosis is the Cdc2 kinase, the first member of the cyclin dependent
      kinase (Cdk) family. Recently, we found that Cdc2 phosphorylates HsEg5, a human
      kinesin-related motor protein associated with centrosomes and the spindle
      apparatus. Our results indicate that phosphorylation regulates the association of
      HsEg5 with the mitotic spindle and that the function of this plus-end directed
      motor is essential for centrosome separation and bipolar spindle formation.
      Another kinase implicated in regulating progression through mitosis is Plk1 (polo
      like kinase 1), the human homologue of the Drosophila gene product "polo." By
      antibody microinjection we have found that Plk1 is required for the functional
      maturation of centrosomes and hence for entry into mitosis. Furthermore, we found
      that microinjected anti-Plk1 antibodies caused a more severe block to cell cycle
      progression in diploid fibroblasts than in immortalized tumor cells. This
      observation hints at the existence of a checkpoint linking Cdc2 activation to the
      presence of functional centrosomes.

PMID- 8986595
TI  - Yeast pre-mRNA is composed of two populations with distinct kinetic properties.
AB  - As an approach to the study of yeast pre-mRNA splicing in vivo, we have examined
      properties of transcripts derived from a gal-UAS intron-containing fusion gene
      encoding RP51A and a series of its derivatives. RNA half-life measurements were
      carried out after transcription initiation was blocked by the addition of
      glucose. Pre-mRNA encoded by GalRP51A decayed with a half-life of approximately 6
      min and was substantially polyadenylated, and transcripts derived from a
      nonspliced version of the same gene decayed with a similar half-life (
      approximately 4 min). A comparison of the steady-state levels of these two
      transcripts suggests that the bulk of GalRP51A pre-mRNA is processed much more
      rapidly, with an average lifetime of about 2 s. We propose that this inferred
      population of rapidly processed molecules is spliced cotranscriptionally and that
      it is the principal precursor to GalRP51A mRNA. Although the pre-mRNA molecules
      detected are therefore unlikely to be the major splicing precursors, an in vivo
      assay suggests that they are likely to have bound splicing factors. They must
      then be spliced much more slowly than most primary transcripts, or not spliced at
      all and then degraded through a different cellular pathway. As a result of its
      comparatively long lifetime, this minor fraction of the pre-mRNA population makes
      up the majority of the steady-state level of GalRP51A pre-mRNA.

PMID- 8986596
TI  - Nuclear organization and gene expression.
AB  - In actively transcribing cells, factors involved in pre-mRNA splicing localize in
      a speckled pattern at the fluorescence microscopic level. The speckled pattern
      corresponds to interchromatin granule clusters and perichromatin fibrils at the
      electron microscopic level. Based upon [3H]uridine incorporation studies
      transcription is thought to occur at the perichromatin fibrils and not within
      interchromatin granule clusters. We have shown that upon inhibition of RNA
      polymerase II transcription or pre-mRNA splicing, splicing factors redistribute
      and preferentially localize to interchromatin granule clusters, which become
      larger and more uniform in shape. Introduction of exogenous DNA templates into
      the cell nucleus results in a recruitment of splicing factors to the new sites of
      transcription. These data suggest that splicing factors are localized at storage
      and/or reassembly sites (interchromatin granule clusters) and are recruited to
      active sites of transcription (perichromatin fibrils). Furthermore, these data
      demonstrate that the speckled localization of pre-mRNA splicing factors is a
      reflection of the transcriptional and pre-mRNA splicing activities of the cell.

PMID- 8986597
TI  - The metaphase chromosome as a reporter of nuclear activity.

PMID- 8986598
TI  - The localization of sites containing nascent RNA and splicing factors.
AB  - Sites of transcription in the HeLa nucleus are not diffusely spread throughout
      euchromatin but are concentrated in approximately 2000 discrete sites or
      "transcription factories." These sites can be immunolabeled after allowing
      permeabilized cells to elongate nascent RNA chains in the presence of BrUTP.
      Splicing factors are also concentrated in a few tens of nuclear domains known as
      "speckles"; they are also more diffusely spread throughout euchromatin. As there
      has been some controversy whether the speckles are sites of transcription, we
      investigated the relative distributions of transcription factories and the
      speckles (detected using Sm autoimmune antibodies). We used conditions that
      minimize the redistribution of both the nascent RNA and the antigens during
      permeabilization and fixation and imaged the sites with high resolution using
      cryosections and a "confocal" microscope. The speckles contained little-if any
      nascent RNA and so were usually not transcriptionally active, but they were often
      surrounded by a few transcription sites. Whether they are active sites of
      processing of RNA or merely sites where the machinery is stored remains to be
      established.

PMID- 8986599
TI  - Regulatory roles of the nuclear envelope.
AB  - Roles of the nuclear envelope are considered in the regulation of nuclear protein
      import, ribonucleoprotein export, and coupling of DNA replication to the cell
      cycle. First, evidence is discussed that indicates that neutral and acidic amino
      acids can be important in nuclear localization signals as well as the widely
      acknowledged basic amino acids. Second, the recognition of nuclear localization
      signals by their receptor "importin" is discussed, focusing on the different
      roles of the two subunits of importin. Third, a role for the alpha subunit of
      importin in RNP export is considered together with the question of how the
      direction of traffic through nuclear pores is determined. The final part of this
      article considers evidence that the nuclear membrane prevents reinitiation of DNA
      replication in Xenopus eggs, by excluding a "licensing factor" that is essential
      for DNA replication. Replication licensing in Xenopus appears to involve several
      proteins including the MCM (minichromosome maintenance) complex and ORC, the
      origin recognition complex, which must bind before the MCM complex can bind to
      chromatin.

PMID- 8986600
TI  - Genetic analysis of macromolecular transport across the nuclear envelope.
AB  - Numerous factors that promote movement of macromolecules in and out of the
      nucleus have now been identified. These include both soluble cytoplasmic and
      nucleoplasmic proteins and proteins of the nuclear pore complex (NPC). Genetic
      analyses of the nuclear transport process in the model organism, the budding
      yeast Saccharomyces cerevisiae, have revealed remarkable conservation of all of
      these factors. In addition, important clues as to how these factors promote the
      unique bidirectional movement across the NPC have emerged from studies of yeast.
      We summarize the characterization and genetic interactions of the soluble
      transport factors and present data to illustrate how genetic experiments can be
      used to further define the import and export pathways.

PMID- 8986601
TI  - Ultrastructure of the nucleus in relation to transcription and splicing: roles of
      perichromatin fibrils and interchromatin granules.
AB  - In the present article we summarize our results concerning the in situ
      ultrastructural organization of the nuclear steps of mRNA production using
      several cellular models including normal noninfected cells, herpes simplex virus
      type 1 and adenovirus type 5 infected cells, and transiently transfected cells.
      We confirm that perichromatin fibrils are the in situ morphological expression of
      nascent transcripts and the main support of splicing. Special emphasis is devoted
      to the clusters of interchromatin granules which seem to be involved in several
      central functions including accumulations of snRNP components as well as sorting
      and/or regulation of export of different RNA species.

PMID- 8986602
TI  - Trans-acting factors in ribosome synthesis.

PMID- 8986603
TI  - Nuclear organization of adenovirus RNA biogenesis.

PMID- 8986604
TI  - Processing of pre-mRNA in polytene nuclei of Chironomus tentans salivary gland
      cells.
AB  - Salivary gland polytene cells in the dipteran Chironomus tentans provide
      exceptional experimental possibilities to analyze processing of specific pre
      mRNAs in intact eukaryotic cell nuclei. Here we give a brief account of how these
      experimental advantages can be exploited to analyze the splicing process in vivo.
      In multi-intron pre-mRNAs, spliceosomes assemble and splicing is initiated
      cotranscriptionally for all introns. Intron excision may, however, occur mainly
      co- transcriptionally or mainly posttranscriptionally depending on the position
      of each intron in relation to the remaining transcription time and intron
      specific efficiencies of excision. As measured for the U2 snRNP and an SR
      protein, 10-15% of the spliceosomal components are bound to pre-mRNA at active
      gene loci at a given moment, while the majority of the spliceosomal components
      are present in the nucleoplasm. A continuous redistribution of the spliceosomal
      components takes place in the nucleus as a result of a close coupling between
      transcription and spliceosomal assembly.

PMID- 8986605
TI  - The topography of chromosomes and genes in the nucleus.
AB  - At present several lines of evidence indicate that the nucleus is functionally
      compartmentalized into discrete structures with defined properties. For instance,
      it is well established that the molecular machines involved in replication,
      transcription, and RNA processing assemble into morphological entities but it
      remains unclear whether these correspond to autonomous "organelles" or rather
      represent temporary accumulations of either active factors recruited onto DNA
      templates or inactive factors stored in the vicinity of genes. According to the
      latter view, the spatial distribution of genes during interphase should play a
      major role in the subnuclear organization of nonchromatin components such as
      replication, transcription, and processing factors, and in this article we
      discuss current ideas on the functional compartmentalization of chromosomes and
      genes within the nucleus.

PMID- 8986607
TI  - Transportin: nuclear transport receptor of a novel nuclear protein import
      pathway.
AB  - Many nuclear proteins are imported into the cell nucleus by the "classical"
      nuclear localization signal (NLS)-mediated import pathway. In this pathway, a
      sequence rich in basic residues in the protein interacts with a heterodimeric
      complex termed importin and this, along with the GTPase Ran, mediates nuclear
      import of the NLS-bearing protein. The heterogeneous nuclear ribonucleoprotein
      (hnRNP) A1 protein contains a novel nuclear localization sequence, termed M9,
      that does not contain any clusters of basic residues. Very recently, we showed
      that M9 directs import into the nucleus by a novel protein import pathway
      distinct from the classical NLS pathway. A 90-kilodalton protein termed
      transportin was identified as a protein that specifically interacts with wild
      type M9 but not transport-defective M9 mutants. Transportin and an ATP
      regenerating system were found to be necessary and sufficient for import of M9
      containing proteins in an in vitro import assay. In this report, we provide
      additional evidence that transportin can interact directly with M9-containing
      proteins and also show that it can mediate import of full-length hnRNP A1. In
      addition, Ran, or a Ran-binding protein, is identified as a second protein
      component of this novel nuclear import pathway. Transportin relatives from
      Saccharomyces cerevisiae which likely serve as additional nuclear transport
      receptors are described.

PMID- 8986606
TI  - The PML and PML/RARalpha domains: from autoimmunity to molecular oncology and
      from retinoic acid to arsenic.
AB  - Acute promyelocytic leukemia (APL) is specifically associated to a t(15; 17)
      translocation which fuses a gene encoding a nuclear receptor for retinoic acid,
      RARalpha, to a previously unknown gene PML. The PML protein is localized in the
      nucleus on a specific domain of unknown function (PML nuclear bodies, NB)
      previously detected with autoimmune sera from patients with primary biliary
      cirrhosis (PBC). These bodies are nuclear matrix-associated and all of their
      identified components (PML, Sp100, and NDP52) are sharply upregulated by
      interferons. We show that autoantibodies against both PML and Sp100 are usually
      associated in sera with multiple nuclear dot anti-nuclear antibodies and
      demonstrate that PML is an autoantigen, not only in PBC, but also in other
      autoimmune diseases. In APL, the PML/RARalpha fusion interferes with both the
      retinoic acid (RA) response and PML localization on nuclear bodies, but the
      respective contribution of each defect to leukemogenesis is unclear. RA induces
      the terminal differentiation of APL blasts, yielding to complete remissions, and
      corrects the localization of NB antigens. Arsenic trioxide (As2O3) also induces
      remissions in APL, seemingly through induction of apoptosis. We show that in APL,
      As2O3 leads to the rapid reformation of PML bodies. Thus, both agents correct the
      defect in NB antigen localization, stressing the role of nuclear bodies in the
      pathogenesis of APL.

PMID- 8986608
TI  - The nucleoskeleton and attached activities.
AB  - This review briefly summarizes recent results obtained on the nucleoskeleton of
      HeLa cells. When the nucleoskeleton is observed in HeLa cells after removal of
      most chromatin using "physiological" conditions, four structural elements can be
      recognized: nuclear lamina, core filaments, diffuse skeleton, and nuclear bodies.
      After dispersing the nucleolar granular component, two additional structures can
      be visualized: the intranucleolar skeleton, and the fibrillar centers. The
      relationship between the nucleoskeleton and nuclear synthetic activities-DNA
      replication and ribosomal transcription-is discussed. The nucleoskeleton is an
      important nuclear structure, involved in nuclear compartmentalization and
      probably critical for replication and transcription.

PMID- 8986609
TI  - Expression of the meiosis-specific synaptonemal complex protein 1 in a
      heterologous system results in the formation of large protein structures.
AB  - The synaptonemal complex is a meiosis-specific structure essential for synapsis
      of homologous chromosomes. The synaptonemal complex protein 1 (SCP1) is a major
      constituent of the transversal filament, a fibrous structure that connects the
      central element of the synaptonemal complex with the two lateral elements. The
      SCP1 protein forms filamentous dimers with the two molecules that have the same
      polarity, with the C-termini being anchored in the lateral elements and the N
      termini reaching into the central element. We investigated whether the SCP1
      protein can take part in the formation of higher order protein structures by
      expressing it in a heterologous system. We find that expression of SCP1 in Swiss
      3T3 fibroblast cells results in the formation of large protein structures. These
      protein structures resemble a higher order protein structure produced by
      overexpression of a yeast transversal filament protein in meiotic cells. Our
      results show that SCP1 is a structural protein and that it most likely is
      directly involved in the assembly of the synaptonemal complex.

PMID- 8986610
TI  - More Sm snRNAs from vertebrate cells.
AB  - There are a number of low-abundance small nuclear RNAs (snRNAs) in eukaryotic
      cells. Many of them have been assigned functions in the biogenesis of cellular
      RNAs, such as splicing and 3' end processing. Here, we present the sequence of
      Xenopus U12 snRNA and compare the secondary structures of the low-abundance U11
      and U12 with those of the high-abundance U1 and U2, respectively. The data
      suggest functional parallels between these two pairs of snRNAs in pre-mRNA
      splicing. Using a highly sensitive method, we have identified several new low
      abundance snRNAs from HeLa cells. These include five U7 snRNA variants and six
      novel snRNAs. One of the six novel RNAs is an Sm snRNA, whereas the rest are not
      immunoprecipitable by either anti-Sm antibodies or anti-trimethylguanosine
      antibodies. The discovery of these new RNAs suggests that there may be yet more
      low-abundance snRNAs in the nuclei of eukaryotic cells.

PMID- 8986611
TI  - Repression of RNA polymerase II and III transcription during M phase of the cell
      cycle.
AB  - Nuclear transcription is repressed when eukaryotic cells enter mitosis. Using
      Xenopus egg extracts shifted to the mitotic state with recombinant cyclin B1
      protein, we have been able to reproduce mitotic repression of transcription in
      vitro. Active RNA polymerase III transcription is observed in interphase extracts
      in the absence of added cyclin, but is strongly repressed by the induction of
      cdc2/cyclin B (maturation/mitosis promoting factor, MPF) kinase activity in the
      mitotic extract. Studies with protein kinase inhibitors show that protein
      phosphorylation is required for repression. Add-back experiments indicate that
      repression of class III gene transcription is due to inactivation of the
      transcription factor TFIIIB. TFIIIB is composed of the TATA-box binding protein
      (TBP) and TBP-associated factors of 75 and 92 kDa. In the present study, we show
      that TBP and a polypeptide of 92 kDa are substrates of the mitotic kinase in
      highly purified TF- IIIB fractions. We also show that a phosphatase present in
      the Xenopus egg extract can reactivate transcription after repression by the
      mitotic kinases. This result suggests a mechanism for reactivation of
      transcription after exit from mitosis into the G1 phase of the cell cycle. As for
      pol III genes, purified cdc2/cyclin B kinase is sufficient to inhibit
      transcription by RNA polymerase II in a reconstituted transcription system
      containing the basal transcription factors and polymerase.

PMID- 8986612
TI  - Intranuclear redistribution of SV40T, p53, and PML in a conditionally SV40T
      immortalized cell line.
AB  - We have previously reported that EBNA-5, one of the Epstein-Barr virus-encoded
      proteins, accumulates in the nuclear bodies containing PML, the promyelocytic
      leukemia associated protein. In this study, we examine the intranuclear
      distribution of SV40 large T-antigen (SV40T), the p53 tumor suppressor protein
      (p53), and PML in a conditionally immortalized cell line, IDH4. In IDH4 cells,
      the expression of SV40T is regulated by a dexamethasone (Dex)-driven promoter.
      Withdrawal of Dex results in down-regulation of SV40T and growth arrest, whereas
      addition of Dex to the growth-arrested cells results in up-regulation of SV40T
      and proliferation. In proliferating IDH4 cells, SV40T is concentrated in nuclear
      dots that are also positive for p53. Many of these dots are juxtaposed to PML
      positive structures but do not colocalize with them. After removal of Dex, SV40T
      p53 dots gradually disappear, while the PML structures remain. Induction of SV40T
      in nonproliferating IDH4 cells causes a coordinated redistribution of SV40T and
      p53. The immunostaining for SV40T and p53 is first weak, then strong with a
      homogeneous distribution, and 3-4 days later becomes dot-like again. This
      reappearance of SV40T-p53 dots coincides with the recovery of proliferation in
      restimulated IDH4 cells. Also, the p53 pattern correlates with the SV40T pattern
      with regard to both morphology and intensity during both suppression and
      induction of SV40T. Taken together, our data suggest that (i) the level of p53 is
      coregulated with the level of SV40T in a dose-dependent fashion; (ii) the
      formation of SV40T-p53 nuclear dots correlates with the transformed phenotype;
      (iii) the SV40T-p53 dots localize preferentially to the neighborhood of PML
      bodies which are already present in normal cells.

PMID- 8986613
TI  - Testis-specific expression of a novel human H3 histone gene.
AB  - We have investigated the expression of a recently described, solitary human H3
      histone gene. Using RNase protection assays, the corresponding mRNA could only be
      detected in RNA preparations from human testis, whereas several human cell lines
      and somatic tissues did not exhibit expression of this gene. In situ
      hybridization of sections from human testis revealed expression to be confined to
      primary spermatocytes. In addition to H1t, this novel H3 gene, which is located
      on chromosome 1, is the second tissue-specific human histone gene that has been
      found to be expressed solely in the testis.

PMID- 8986614
TI  - Focal adhesion and stress fiber formation is regulated by tyrosine phosphatase
      activity.
AB  - Tyrosine phosphorylation of cytoskeletal proteins plays an important role in the
      regulation of focal adhesions and stress fiber organization. In the present study
      we examined the role of tyrosine phosphatases in this process using p125FAK and
      paxillin as substrates. We show that tyrosine phosphatase activity in Swiss 3T3
      cells was markedly increased when actin stress fibers were disassembled by cell
      detachment from the substratum, by serum starvation, or by cytochalasin D
      treatment. This activity was blocked by phenylarsine oxide, an inhibitor of a
      specific class of tyrosine phosphatases characterized by two vicinal thiol groups
      in the active site. Phenylarsine oxide treatment of serum-starved cells induced
      increased tyrosine phosphorylation of p125FAK and paxillin in a dose-dependent
      manner and induced assembly of focal adhesions and actin stress fibers, showing
      that inhibition of one or more phenylarsine oxide-sensitive tyrosine phosphatases
      is a sufficient stimulus for triggering focal adhesion and actin stress fiber
      formation in adherent cells.

PMID- 8986615
TI  - Differential regulation of gap junction protein (connexin) genes during
      cardiomyocytic differentiation of mouse embryonic stem cells in vitro.
AB  - Using an in vitro system for differentiation of embryonic stem (ES) cells into
      cardiac myocytes, we analyzed the expression of connexin (Cx) genes by RT-PCR to
      learn what changes in the expression of multiple connexin genes occur during the
      early stage of heart development. We also examined gap junctional intercellular
      communication by using Lucifer Yellow dye microinjection transfer, studied
      intracellular Ca2+ transients by confocal laser image analysis using fluo 3, and
      determined localization of Cx43 by immunofluorescence during in vitro
      differentiation of ES cells into cardiac myocytes. The transcripts for Cx43 and
      Cx45 were detected in undifferentiated ES cells and in embryoid bodies before and
      after the appearance of beating cardiomyocytes. In contrast, Cx40 transcripts
      were not observed in undifferentiated ES cells and were barely detectable in 3-
      and 5-day-old embryoid bodies. Cx40 transcripts significantly increased with the
      appearance of beating cells similar to those of cardiac-specific genes. Dye
      coupling was present among undifferentiated ES cells, prebeating cells of
      embryoid body outgrowth and ES cell-derived beating cardiomyocytes. When dye was
      injected into a beating cell, dye spread was restricted to neighboring beating
      cells. Immunofluorescence demonstrated that Cx43 protein was localized not only
      in beating cells but also in surrounding nonbeating cells, whereas myosin heavy
      chain alpha/beta was exclusively positive in the beating cells. These data
      suggest that the expression of multiple connexins is differentially regulated
      during the cardiomyocytic differentiation of ES cells in vitro and that Cx40
      expression may be linked to early stages in cardiomyocytic differentiation.

PMID- 8986616
TI  - Bistratene A causes phosphorylation of talin and redistribution of actin
      microfilaments in fibroblasts: possible role for PKC-delta.
AB  - Bistratene A is a marine toxin which induces phosphorylation of cellular
      proteins. Our current evidence indicates that this occurs through activation of
      protein kinase C-delta. In fibroblasts bistratene A causes rounding up of the
      cells and a rapid disappearance of vinculin staining and actin stress fibers as
      detected by fluorescence immunohistochemistry. Phosphorylation of the focal
      adhesion protein, talin, is increased after bistratene A treatment and this is
      inhibited by calphostin C, a specific inhibitor of PKC. No changes in the
      phosphorylation status of vinculin, tubulin, or vimentin were observed in the
      presence of the toxin. Treatment with bistratene A caused a redistribution of PKC
      delta from cytosolic and membrane compartments to the nuclear fraction. There was
      no effect on the subcellular distribution of any other PKC isoform. These results
      demonstrate that phosphorylation of talin is implicated in the disruption of
      actin microfilaments in fibroblasts by bistratene A and that this is most likely
      mediated by PKC-delta.

PMID- 8986617
TI  - Recruitment of type I collagen producing cells from the microvasculature in
      vitro.
AB  - We have previously suggested that microvascular pericytes can differentiate into
      fibroblast-like, type I collagen-producing cells during excessive dermal scarring
      in vivo (Sundberg, C., Ivarsson, M., Gerdin, B., and Rubin, K., Lab. Invest. 74,
      454-468, 1996). Here we have investigated to what extent pericytes derived from
      microvessels of full-term human placenta exhibited this capacity in vitro.
      Vascular fragments of human term placenta were isolated by enzymatic digestion
      and separation in Percoll. Their microvascular origin was ascertained by confocal
      microscopy using antibodies specific for endothelial cells (PAL-E) and pericytes
      (high-molecular-weight-melanoma-associated antigen). When vascular fragments were
      cultured in vitro, large cells with irregular edges migrated out from the
      fragments. After 4-6 days in culture, these cells started to proliferate and
      reached near confluence after approximately 8 days. The cultures were not
      overgrown by clones of cells with a high proliferative capacity, as demonstrated
      by cell membrane fluorescence staining and Ki67 expression. Expression of PAL-E,
      high-molecular-weight-melanoma-associated antigen, smooth muscle alpha-actin,
      desmin, and collagen synthesis (prolyl-4-hydroxylase and type I procollagen, as
      well as collagen pro-alpha1(I) mRNA) were followed during a culture period of 8
      days. The cells were PAL-E negative but expressed high-molecular-weight-melanoma
      associated antigen, smooth muscle alpha-actin, and desmin. Based on morphology
      and expression of the various markers, the outgrowing cells were identified as
      pericytes. With time in culture the cells decreased their expression of all these
      markers and increased their expression of prolyl-4-hydroxylase, type I
      procollagen, and collagen pro-alpha1(I) mRNA. Metabolic labeling and SDS-PAGE
      analysis of labeled proteins revealed that type I collagen was the major collagen
      species synthesized in the cultures. Our results support the hypotheses that
      pericytes can leave the vasculature and differentiate into collagen-producing
      cells and that cultured "fibroblasts" are derived from pericytes.

PMID- 8986618
TI  - Individual nuclei differ in their sensitivity to the cytoplasmic inducers of DNA
      synthesis: implications for the origin of cell cycle variability.
AB  - Nuclei of multinucleate cells generally initiate DNA synthesis simultaneously,
      suggesting that the timing of DNA synthesis depends upon the appearance of a
      cytoplasmic signal. In contrast, intact nuclei from quiescent mammalian cells
      initiate DNA synthesis asynchronously in cell-free extracts of Xenopus eggs,
      despite the common environment. Here we show that the two nuclei of permeabilized
      binucleate cells enter DNA synthesis coordinately in egg extracts, as they do in
      vivo, with different pairs of nuclei initiating replication at different times.
      This indicates that the two nuclei of a binucleate cell are identical in their
      sensitivity to the inducers of DNA synthesis in egg extracts; this sensitivity
      varies in general between the nuclei of unrelated cells. The asynchrony of DNA
      synthesis shown by unrelated nuclei in egg extracts is therefore not an artifact
      of the cell-free system but a reflection of genuine differences preexisting
      within the intact cell. Evidence that these differences between nuclei are
      responsible for a substantial fraction of G1 variability in living cells is
      presented.

PMID- 8986619
TI  - Extracellular matrix penetration by epithelial cells is influenced by
      quantitative changes in basement membrane components and growth factors.
AB  - We have previously shown that isolated mouse fetal choroid plexus epithelial
      (CPE) cells penetrate a basement membrane matrix (Matrigel) substrate in vitro to
      form single-layered epithelial vesicles embedded within the matrix. To determine
      which properties of the matrix are important for inducing or permitting cells to
      penetrate the substrate and organize into multicellular vesicles we have made
      quantitative changes to the basement membrane components and growth factors in
      cell cultures. Matrigel diluted to 33 or 10% with a collagen I gel was not
      permissive to cell invasion, and CPE cells formed a polarized epithelial
      monolayer on the substrate surface which had ultrastructural characteristics
      similar to those of CPE vesicles. Cells in these monolayers proliferated more
      rapidly than cells in epithelial vesicles. When deliberately embedded within a 33
      or 10% Matrigel matrix, CPE cells were able to form vesicles, indicating that a
      dilute matrix is nonpermissive to cell invasion but promotes epithelial
      polarization and organization into vesicles. Cells embedded within a 100%
      collagen I matrix did not proliferate or form epithelial vesicles and the
      majority of cells did not remain viable. Addition of laminin to the collagen I
      gel promoted cell adhesion and cell survival, but did not promote the formation
      of extensive monolayers on the substrate nor the formation of epithelial vesicles
      within the matrix. Cell invasion into the 33% Matrigel matrix was induced by
      addition of laminin, nidogen, or a laminin-nidogen complex to the substrate or by
      addition of TGFbeta2 to the culture medium, but not TGFbeta1 or PDGF. These
      studies show that CPE cells are sensitive to quantitative changes in matrix
      composition, which influences their survival and proliferation and also their
      ability to penetrate the matrix and organize into multicellular epithelial
      vesicles.

PMID- 8986620
TI  - Spontaneous apoptosis of thymocytes is uncoupled with progression through the
      cell cycle.
AB  - Most developing lymphocytes spontaneously die in the thymus during positive and
      negative selection of the T cell repertoire. By evaluating the expression of the
      proliferation antigens Ki-67 and PCNA, we demonstrated here that more than 95% of
      thymocytes are potentially proliferating. The coincidence within the same cell
      population of death and proliferation is thus apparent in developing thymocytes.
      Using dual-parameter cytometric techniques to evaluate in single cells the amount
      of DNA versus light-scattering values, we found that spontaneous thymocyte
      apoptosis occurs with similar frequency in all the cycle phases, whereas
      apoptosis induced by the anti-topoisomerase-II, etoposide (which is the
      consequence of irreversible DNA damage), takes place with higher frequency in S
      and G2 phases (i.e., in those cycle phases in which DNA is subjected to torsional
      constraints). The capability of thymocytes to enter apoptosis was also monitored
      by digesting DNA in situ with DNase I (a nuclease that cleaves DNA mimicking the
      nuclear damage common to most apoptotic suicides). We also show that endonuclease
      mediated DNA digestion occurs to a similar extent in cells with different DNA
      contents, i.e., in cycle phases in which the superstructural organization of
      chromatin is markedly different.

PMID- 8986621
TI  - Tau-like proteins associated with centrosomes in cultured cells.
AB  - The subcellular association of tau-like proteins with centrosomes in cultured
      cell lines and its effects in nucleating microtubule assembly were analyzed using
      biochemical and immunocytochemical approaches. Tau proteins, major components of
      microtubules, appear to be tightly associated with actin filaments in a variety
      of cell lines, while in pathological conditions of neurons, they are part of
      paired helical filaments found in Alzheimer's disease. Different studies suggest
      that, in addition to tau interactions with the components of the cytoskeletal
      network, tau polypeptides appear to be associated with highly structured cellular
      elements, in both interphase and mitotic cells. An in-depth analysis of tau
      subcellular distribution us- ing different polyclonal and monoclonal antibodies
      showed colocalization of tau-like components with centrosomes in interphase cells
      of the human Huh-7 hepatoma, in SW-13 adenocarcinoma, and in normal human
      fibroblasts. Tau associated with centrosomes in mitotic Huh-7 cells was also
      identified. However, antibodies against the tau binding repeats did not stain
      centrosomes. A set of different tau isoforms was also identified by Western blot
      analysis on isolated centrosomal preparations from Huh-7 cells, obtained by
      differential centrifugation through sucrose gradients. Microtubule nucleation in
      vitro over isolated centrosomes was inhibited by both the polyclonal antibody
      against native tau and an antibody to the N-terminal tau sequence, as revealed by
      immunofluorescence analysis and assembly kinetics experiments. The antibody
      TRS1.2 against the fragment containing the first binding repeat on tau did not
      affect nucleation. These studies allowed us to characterize tau association with
      the isolated centrosomal preparation and its involvement in microtubule assembly
      nucleated over centrosomes, thus suggesting possible structural and functional
      roles for these interactions.

PMID- 8986622
TI  - A chondroitin/dermatan sulfate form of CD44 is a receptor for collagen XIV
      (undulin).
AB  - Collagen XIV, a fibril-associated collagen with interrupted triple helices, is
      expressed in differentiated soft connective tissues and in cartilage. However, a
      cellular receptor for this protein has not been identified. Here we show that
      human placental collagen XIV, isolated by a mild and simple two-step method,
      serves as adhesive protein for a variety of mesenchymal and some epithelial
      cells. Cell adhesion could be inhibited by preincubation of the collagen XIV
      substrate with heparin or with the chondroitin/dermatan sulfate proteoglycan
      decorin and by pretreatment of cells with chondroitinase ABC or heparinase III,
      suggesting a cell membrane proteoglycan as receptor. Affinity chromatography of
      125I-labeled fibroblast cell surface proteins on collagen XIV-Sepharose yielded a
      chondroitin/dermatan sulfate proteoglycan with a molecular mass of 97-105 kDa
      after chondroitinase ABC digestion and of 60-70 kDa after further treatment with
      N-glycosidase F. The eluates contained also some high-molecular-weight material
      that was susceptible to digestion with heparinase but no detectable integrins.
      Immunoprecipitation with a specific monoclonal antibody identified the prominent
      chondroitin/dermatan sulfate proteoglycan as a member of the CD44 family. The
      interaction between collagen XIV and cells appears to be finely tuned, since
      matrix-associated glycosaminoglycans, and particularly proteoglycans like
      decorin, could compete with cells for the binding site(s) on collagen XIV under
      physiological conditions.

PMID- 8986623
TI  - Heparan sulfate proteoglycans play a dual role in regulating fibroblast growth
      factor-2 mitogenic activity in human breast cancer cells.
AB  - The human breast cancer cell lines MCF-7 and MDA-MB-231 differ in their
      responsiveness to fibroblast growth factor-2 (FGF-2). This growth factor
      stimulates proliferation in well-differentiated MCF-7 cells, whereas the less
      well-differentiated MDA-MB-231 cells are insensitive to this molecule. To
      investigate the potential regulation of FGF-2 mitogenic activity by heparan
      sulfate proteoglycans (HSPG), we have treated human breast cancer cells by
      glycosaminoglycan degrading enzymes or a metabolic inhibitor of proteoglycan
      sulfation: sodium chlorate. The interaction between FGF-2 and proteoglycans was
      assayed by examining the binding of 125I-FGF-2 to breast cancer cell cultures as
      well as to cationic membranes loaded with HSPG. Using MCF-7 cells, we showed that
      heparinase treatment inhibited FGF-2 binding to HSPG and completely abolished FGF
      2 induced growth; chlorate treatment of MCF-7 cells decreased FGF-2 binding to
      HSPG and cell responsiveness in a dose-dependent manner. This demonstrates a
      requirement of adequately sulfated HSPG for FGF-2 growth-promoting activity on
      MCF-7 cells. In highly invasive MDA-MB-231 cells which produce twice as much HSPG
      as MCF-7 cells and which are not normally responsive to exogenously added FGF-2,
      chlorate treatment decreased FGF-2 binding to HSPG and induced FGF-2 mitogenic
      effect. This chlorate effect was dose dependent and observed at concentrations of
      10-30 mM; higher chlorate concentrations completely abolished the FGF-2 effect.
      This shows that the HSPG level of sulfation can also negatively regulate the
      biological activity of FGF-2. Taken together, these results demonstrate a crucial
      role for HSPG in both positive and negative control of FGF-2 mitogenic activity
      in breast cancer cell proliferation.

PMID- 8986624
TI  - Localization of the newly initiated and processed ribosomal primary transcripts
      during the mitotic cycle in Physarum polycephalum.
AB  - We analyzed the fate of the rRNA released as a result of the prophasic
      disintegration of the nucleolus, during the "closed" mitosis of the naturally
      synchronous plasmodium of Physarum polycephalum. Using a probe complementary to
      the mature 19S and 26S rRNA, we previously showed that the nucleolus-derived
      rRNAs are stable in mitosis, mainly associated with numerous fibrillar nucleolar
      remnants (Pierron and Puvion-Dutilleul, 1993, Exp. Cell Res. 208, 509-517).
      However, a significant fraction of these mitotic rRNA precursors were also found
      in more diffuse nuclear, granular zones. In this paper, we trace pre-rRNA
      molecules in the early stages of their maturation by using probes derived from
      the 5' external transcribed spacer (5'-ETS), upstream and downstream of the
      processing site located 1.7 kb from the transcription initiation site. In
      agreement with a previous S1-mapping study (Blum et al., 1986, Nucleic Acids
      Res., 10, 4121-4133), we observed that the rRNA transcripts complementary to the
      5'-ETS portion downstream of the processing site are stable in mitosis, and we
      demonstrate that they are specifically associated with the border of the
      fibrillar nucleolar remnants. On the other hand, the pre-rRNA chains containing
      the upstream portion of the 5'-ETS become undetectable in mitosis, marking the
      cessation of rDNA transcription. Since the reappearance of these nascent pre-rRNA
      molecules signals the resumption of the transcriptional activity, we determined
      that a burst of rRNA synthesis is taking place within the prenucleolar bodies,
      immediately after the separation of the daughter nuclei. Taken together, our
      results illustrate the persistence of the nucleolar components of Physarum,
      within nucleolar remnants that, although transcriptionally inactive during
      mitosis, function as independent entities very early in interphase.

PMID- 8986625
TI  - Role of N-myristylation in targeting of band 4.2 (pallidin) in nonerythroid
      cells.
AB  - Band 4.2 (pallidin) is a major erythrocyte membrane protein which has been
      detected in a number of nonerythroid cell types. Increasing evidence suggests
      that band 4.2 is involved in maintaining membrane stability in the erythrocyte.
      For example, band 4.2 binds to the integral membrane protein band 3 and to
      cytoskeletal proteins in the erythrocyte membrane, and band 4.2 deficiency
      results in varying degrees of hemolytic anemia. We have previously shown that
      human erythrocyte band 4.2 is myristylated at its penultimate glycine. Here we
      report that when expressed in both Sf9 and COS cells, myristylated forms of band
      4.2 are detected at different intracellular locations than nonmyristylated forms.
      We also show that the unspliced form of human erythrocyte band 4.2 (a minor form
      in reticulocytes which contains an additional 30 amino acids after the first
      three N-terminal amino acids compared to the major erythroid form) is
      myristylated only at a barely detectable level, while mouse erythrocyte band 4.2
      (homologous to the major erythroid form of human band 4.2) is myristylated at a
      level comparable to that of human band 4.2. These results suggest that
      myristylation plays a key role in the targeting of band 4.2 to specific
      intracellular locations and is likely to have a role in the function of this
      protein.

PMID- 8986627
TI  - BCR-ABL induces neurite-like structures and BCR lacking the SH2-binding domain
      induces cell rounding in PC12 cells.
AB  - The activated tyrosine kinase oncoprotein BCR-ABL is responsible for pathogenesis
      of Philadelphia chromosome-positive human leukemias. Because BCR carries a GAP
      (GTPase-activating protein) activity toward cytoskeleton-related small GTP
      binding proteins, we utilized a neuronal PC12 cell system to test morphogenic
      potentials of BCR-ABL or BCR. We report here unique morphological phenotypes of
      PC12 cells expressing either BCR-ABL or a BCR mutant which lacks the SH2-binding
      domain (BCR Delta162-413). Although MAP kinase was not activated in PC12 cells
      expressing BCR-ABL, they showed incomplete neurite extensions even in the absence
      of the nerve growth factor (NGF). Overproduction of BCR Delta162-413 in PC12
      cells, on the other hand, induced cell rounding in the absence of NGF.
      Interestingly, those cells could hardly make terminal differentiation in the
      presence of NGF and continued to grow without changing their round shape,
      although NGF receptor as well as MAP kinase appeared to be activated.
      Interestingly, the botulinum C3 toxin induced neurite-like structures in PC12
      cells overexpressing BCR Delta162-413 without NGF.

PMID- 8986626
TI  - Age-associated changes in basal c-fos transcription factor binding activity in
      rat hearts.
AB  - The early response proto-oncogene c-fos is expressed at very low levels in the
      mammalian heart at baseline. To further investigate the mechanism of altered c
      fos expression with age, we studied in the basal state the binding of five
      transcription proteins to their cognate sites in the c-fos promoter/enhancer
      region, in adult and old F344 rats. Our results show a reduced binding of E2F and
      AP1 proteins to the c-fos promoter in aging hearts. The major calcium/cyclic AMP
      response element (CRE) and SP1 binding was unchanged. The only increase seen with
      age was in the serum response element (SRE) binding proteins. SRE is the point of
      convergence of different signal transduction pathways (via MAP kinases and the
      Rho family of GTPases) at the c-fos promoter. Increased SRE binding may reflect a
      compensation for a decreased binding of other transcription proteins to the c-fos
      promoter, alteration in the phosphorylation status of SRF, or a change in the
      ternary complex factors Elk 1 or SAP 1. Other possibilities include defects in
      the signal transduction pathways with aging, which combine to produce an overall
      negative balance in the function of the c-fos promoter despite the increased SRE
      binding activity. Both in vitro and in vivo experiments have shown decreased c
      fos expression with age. This may be due partly to alterations in the basal
      levels of transcription factor binding.

PMID- 8986628
TI  - Free ricin A chain reaches an early compartment of the secretory pathway before
      it enters the cytosol.
AB  - During the intoxication of mammalian cells by ricin, the catalytically active A
      chain must cross the membrane of an intracellular compartment in order to reach
      its ribosomal substrates in the cytosol. The actual site of ricin A chain
      translocation is unclear, and conflicting views hold that it enters the cytosol
      from endosomes or from an early compartment of the secretory pathway, possibly
      the lumen of the endoplasmic reticulum. Here we show that treating cells with
      brefeldin A, or transiently overexpressing mutant GTPases known to inhibit
      biochemical complexes mediating anterograde and retrograde transport between the
      endoplasmic reticulum and the Golgi complex, protected cells from intoxication by
      free ricin A chain. These data indicate that ricin A chain, either free or as
      part of intact ricin, reaches an early compartment of the secretory pathway
      before translocation into the cytosol occurs.

PMID- 8986629
TI  - Apoptosis and free radicals.
AB  - Free radicals that appear during physiological processes may lead to apoptosis in
      some pathological conditions when antioxidant capacity of the tissue is
      surpassed. Additionally, free radicals are involved in the control of apoptosis;
      antioxidant agents suppress apoptosis induced by a variety of stimuli. The
      possibility that apoptosis is regulated by modulation of the levels of free
      radicals is discussed.

PMID- 8986630
TI  - In search of a gene for hereditary cholestasis.

PMID- 8986631
TI  - The influence of dietary folate and methionine on the metabolic disposition of
      endotoxic homocysteine.
AB  - We have investigated the disposition of potentially endotoxic homocysteine (Hcy)
      and its transsulfuration metabolite cysteine (Cys) in 98 individuals (age range
      20-66 years). Our study reports on the relationship between Hcy and two important
      dietary factors likely to influence plasma levels of this thiol: dietary folate
      and dietary methionine. chi2 analysis shows a low frequency of elevated plasma
      Hcy at high folate intake. This frequency for Hcy >10 micromol/liter with a
      folate intake >350 microg/day is significant (P < 0.02). The data reflect a
      tendency for elevated Hcy values to be associated with low dietary folate,
      although many subjects with a low dietary folate also had a low plasma Hcy.
      Intake of dietary methionine was found to be significantly higher in males than
      in females (P < .0001). This may account for the looser relationship between Hcy
      and its transsulfuration product, Cys, in females (R2 = 0.30) compared to males
      (R2 = 0.73), since conversion of methionine to SAM in males would activate
      cystathionine beta synthase and commit excess Hcy to transsulfuration. The
      generally lower methionine intake of females means that more Hcy is utilized in
      the remethylation cycle in which methionine is produced from the de novo methyl
      group of 5-methyltetrahydrofolate or from the preformed methyl group of betaine.
      Clearly a Hcy moiety locked up in remethylation would be further removed from
      Cys, the end product of transsulfuration. An increasing number of studies are
      clarifying the relationship between Hcy, folate, and other B vitamins. However,
      less attention seems to be given to the influence of dietary methionine on the
      disposition of Hcy. The present study supports biochemical theory and indicates
      that more focus should be given to the effect of dietary methionine on Hcy. These
      findings have particular significance since even moderate increases in plasma Hcy
      are associated with a toxic vascular effect. Consequently the relationship
      between dietary folate and Hcy levels should be a factor in evaluating
      recommended dietary allowances for this vitamin. The simplicity of our dietary
      folate questionnaire also raises the possibility of a screening test in which
      individuals can ascertain whether their folate intake is adequate to reduce Hcy
      levels to a benign value.

PMID- 8986632
TI  - Dideoxyfingerprinting (ddF) analysis of the type X collagen gene (COL10A1) and
      identification of a novel mutation (S671P) in a kindred with Schmid metaphyseal
      chondrodysplasia.
AB  - Schmid metaphyseal chondrodysplasia (SMCD; MIM 156500) is an autosomal dominant
      disorder of the skeleton that is manifested in early childhood by short stature,
      coxa vara, and a waddling gait. Patients with SMCD have mutations in the gene
      that codes for the alpha-1 chain of collagen X (COL10A1); however, mutation
      analysis of this gene is hampered by its size. We studied a family with SMCD: the
      mother, a 36-year-old woman with a height of 149 cm, had mild bilateral coxa
      vara. Her two sons presented with short stature, bowed legs, and coxa vara in
      early childhood. DNA was extracted from peripheral lymphocytes from the three
      patients and subjected to PCR amplification by COL10A1 gene-specific primers. In
      addition to single-strand conformational polymorphism (SSCP) analysis of the
      COL10A1 gene, we used a novel method, dideoxy fingerprinting (ddF). The genetic
      defect in this family was found to be a previously unreported missense mutation
      (T-to-C transition) at nucleotide 2011. This change resulted in a Ser-to-Pro
      substitution at position 671 of the carboxy-terminus of the COL10A1 protein. In
      addition, the two boys, but not the mother, were found to carry a trinucleotide
      (CCC) deletion at position 2048 of the 3' untranslated region, a polymorphism of
      the COL10A1 gene. We conclude that ddF can be used in the analysis of the COL10A1
      gene along with SSCP. The S671P substitution is novel, but located in the same
      region with the other reported COL10A1 mutations, confirming type X collagen as
      the locus for this disease.

PMID- 8986633
TI  - Phospholipid hydroperoxide glutathione peroxidase (PHGPx) in rat testis nuclei is
      bound to chromatin.
AB  - In rat testis nuclei the activity of the selenoenzyme phospholipid hydroperoxide
      glutathione peroxidase (PHGPx, EC 1.11.1.12) is much higher than in other tissues
      and subcellular compartments, with the sole exception of mitochondria. In nuclei,
      the bound enzyme is solubilized by DNase I treatment, thus suggesting a binding
      to chromatin. Treatment with ionic strength releases about 70% of bound PHGPx,
      suggesting that electrostatic bonds are involved. Immunogold electron microscopy
      indicates the association of PHGPx with chromatin structures in isolated nuclei.
      A possible interpretation of these data is a PHGPx protective role against DNA
      peroxidative damage. Furthermore, in agreement with kinetic and structural
      information, PHGPx-chromatin binding could suggest an hypothetical thiol oxidase
      activity toward specific thiol bearing proteins which could substitute for GSH as
      alternative donor substrates. Such activity could give to the enzyme a new
      important function which is not only protective but also has a specific
      regulatory function in chromatin condensation.

PMID- 8986634
TI  - The glucocerebrosidase D409H mutation in Gaucher disease.
AB  - Gaucher disease, resulting from the decreased activity of the lysosomal enzyme
      glucocerebrosidase, is the most prevalent sphingolipid storage disease. Due to
      considerable heterogeneity of phenotypic expression, it has been subdivided into
      the nonneurological type 1 disease, and types 2 and 3, the neurological types. We
      describe homozygosity for the D409H mutation within the glucocerebrosidase gene
      associated with a unique form of type 3 Gaucher disease. Twelve patients,
      originating from three Arab sibships, were found to be homozygous for the D409H
      mutation. They all presented with oculomotor apraxia and a progressive cardiac
      valve defect with minimal organomegaly. When expressed in human cells in tissue
      culture, using the T7/EMC/vaccinia virus hybrid expression system, we were able
      to demonstrate that the mRNA carrying the D409H mutation was less stable than the
      normal counterpart. Pulse-chase experiments demonstrated that the mutated protein
      exhibited lower stability than the normal counterpart. Its activity toward the
      artificial substrate 4-methyl umbelliferyl glucopyranoside was similar to that of
      the mutated enzymes carrying the N370S or the L444P mutations. However, in
      loading experiments using lissamine-rhodamine conjugated glucosyl ceramide as a
      substrate, the recombinant mutated protein carrying the D409H mutation exhibited
      28.63 +/- 6.05% of the activity exhibited by the normal enzyme. L444P and N370S
      mutations exhibited 51.90 +/- 7.16 and 115.75 +/- 12.64% of normal enzyme
      activity, respectively. Loading of cells homozygous for the D409H mutation
      demonstrated 10. 05% of the activity shown by normal cells. L444P and N370S
      homozygous cells demonstrated 25.3 and 98.5% of foreskin fibroblast
      glucocerebrosidase activity, respectively. We demonstrate that homozygosity for
      the D409H mutation is a unique case of a peculiar phenotype associated with a
      specific intracellular glucocerebrosidase activity.

PMID- 8986635
TI  - Diagnosis of complex I deficiency in patients with lactic acidemia using skin
      fibroblast cultures.
AB  - The requirement for a rapid and easy method of preparing mitochondrial fractions
      from cultured skin fibroblasts led us to compare the results obtained from such a
      preparation with the more traditional methods of cellular fractionation. Values
      for NADH-cytochrome c reductase (rotenone sensitive) were compared for a series
      of three controls and nine patients with complex I (NADH-coenzyme Q reductase
      deficiency). Values obtained for deficient cell lines varied from 19 to 64% of
      the control values for the long mitochondrial preparation method and from 34 to
      70% of control for the rapid preparation. Mean values were statistically
      significantly different from the lowest control cell line (P < 0.01) in all
      cases. The specific activity on the basis of activity per milligram of
      mitochondrial protein and of activity per unit of citrate synthase activity was
      lower in the rapid preparation of mitochondria by some 41%, indicating a lesser
      degree of mitochondrial purification. However, the overall result showed that
      this type of rapid preparation, which uses four 9-cm petri dishes of cultured
      cells, can be used to diagnose mitochondrial complex I deficiency. This method
      will find general use in the measurement of either mitochondrial enzymes of low
      specific activity or mitochondrial enzymes whose measurement is made difficult by
      contaminating nonmitochondrial enzymes.

PMID- 8986636
TI  - Stimulation of interleukin-1beta-independent interleukin-6 production in human
      dental pulp cells by lipopolysaccharide.
AB  - Dental pulpal infection is most commonly caused by extensive dental caries. A
      principal driving force behind pulpal disease response appears to lie in the
      immune system's response to bacteria. However, the production of interleukin (IL)
      1beta and IL-6 in human dental pulp (HDP) cells in response to lipopolysaccharide
      (LPS) has not been well characterized. We examined IL-1beta and IL-6 production
      in HDP cells by challenging with LPS from Porphyromonas endodontalis, which is a
      Gram-negative bacteria found in root canals. Our results presented here showed
      that when HDP cells were stimulated by LPS, the production of IL-6 always
      preceded that of IL-1beta. Since the IL-6 production was observed even in the
      presence of the IL-1beta receptor antagonist, we concluded IL-6 production was
      independent of the IL-1beta molecule in LPS-stimulated HDP cells. This idea was
      further supported by the results obtained from RT-PCR experiments, in which IL-6
      mRNA, but not IL-1beta mRNA, was present in the RNA preparation isolated from the
      early stage of cells.

PMID- 8986638
TI  - Differential effects of insulin-like growth factor-1 on neonatal canine gene
      expression.
AB  - To determine the effects of insulin-like growth factor-1 (IGF-1) and amylin on
      glucose homeostasis in vivo in newborn dogs, euglycemic hyper-IGF-1 clamps and
      hypoglycemic hyper-IGF-1 clamps were performed in newborn dogs. Northern blotting
      and radioimmunoassays were used to study the effects of the infused IGF-1 and/or
      hypoglycemia on the mRNA expression of the genes for phosphoenolpyruvate
      carboxykinase (PEPCK) and on the expression of the amylin gene in newborn dogs.
      Our results were that (1) Infused IGF-1 (plasma IGF-1 >/=1000 ng/ml) rapidly
      lowered the plasma glucose level, and 120 +/- 38 mg glucose/pup was co-infused
      during a 105-min clamp to maintain the plasma glucose at the basal level. (2) The
      infused IGF-1 rapidly reduced the liver cytosolic mRNA for the PEPCK gene to an
      almost undetectable level. (3) Hyper-IGF-1 had no effect on mRNA level of the
      amylin gene in pancreas, 106.7 +/- 14.2% vs 100.0 +/- 5.9% (controls), or on
      plasma amylin concentration, 56. 0 +/- 5.7 pg/ml vs 52.1 +/- 5.7 pg/ml (basal).
      (4) The amylin mRNA level, 127.8 +/- 3.9% vs 100.0 +/- 5.9% (controls) (P =
      0.017), and the plasma amylin concentration, 132.3 +/- 18.3 pg/ml vs 110.0 +/-
      10.8 pg/ml (controls) (P = 0.371), showed a parallel stimulation by hypoglycemia
      in the presence of hyper-IGF-1. We concluded that (1) IGF-1 acutely suppressed
      cytosolic PEPCK gene expression in liver of newborn dogs. (2) IGF-1 does not
      effect the expression of the pancreatic amylin gene. (3) Amylin may be involved
      in glucose homeostasis in newborn dogs and may play a role as a counterregulatory
      factor during the neonatal period. Unsuppressed amylin production may contribute
      to neonatal hyperglycemia.

PMID- 8986637
TI  - Toxicity of cationic lipid-ribozyme complexes in human prostate tumor cells can
      mimic ribozyme activity.
AB  - Prostate tumor cell lines have been shown to both produce interleukin-6 (IL-6)
      and express the IL-6 receptor, suggesting a potential autocrine growth regulatory
      role for IL-6. We explored the role of IL-6 in the proliferation of the human
      prostatic carcinoma cell line, DU145, using ribozymes to inhibit IL-6 expression.
      Hammerhead-type ribozymes targeted against IL-6 mRNA sequences were prepared, and
      in vitro analyses were used to demonstrate that these molecules catalyzed the
      cleavage of IL-6 mRNA poly- nucleotide fragments. To test in situ activity, these
      ribozymes were transfected into DU145 cells using cationic transfection lipids,
      cytofectins. Treatment of cultured cells with ribozyme/cationic lipid complexes
      resulted in a reduction of IL-6 protein levels in the supernatant and reduced
      numbers of DU145 cells 48 h after treatment. However, similar results were also
      seen following treatment with control RNA/lipid complexes. This reduction in IL-6
      levels and cell numbers was a function of the RNA/lipid complexes and was not
      seen with either lipid or RNA alone. Therefore, the reductions in IL-6 levels and
      cell numbers observed were not due to ribozyme-mediated cleavage of IL-6 mRNA,
      but rather reflected a dose-dependent, nonspecific toxic effect of the treatment
      with ribozyme/cytofectin complexes. This effect can resemble functional ribozyme
      activity, complicating analysis of the activity of synthetic ribozymes after
      transfection into cultured cells.

PMID- 8986639
TI  - A new type of major aminopeptidase in bovine brain.
AB  - A new type of major aminopeptidase was purified from bovine brain by ammonium
      sulfate fractionation and TMAE-fractogel (anion exchange), arginine-Sepharose 4B,
      Sephadex G-150, and Sephadex G-100 column chromatography. The purified enzyme
      showed a maximum activity at pH 7.2, and its molecular size was estimated to be
      98,000 by gel filtration and 104,000 by SDS-PAGE with or without 2
      mercaptoethanol. Further properties were activation by thiol reagents; inhibition
      by EDTA, puromycin, bestatin, amastatin, actinonin, leuhistin and probestin; and
      very low concentrations of Cu2+, Cd2+, Pb2+, Al3+, Fe3+, and Zn2+ inhibited
      activity. The enzyme hydrolyzed several amino acyl-7-amido-4-methylcoumalin
      derivatives (amino acid-MCA). The order of MCA-substrate specificity expressed as
      kcat/Km is Lys-MCA > Arg-MCA > Leu-MCA > Met-MCA > Phe-MCA > Tyr-MCA > Ala-MCA >>
      Gly-MCA, Pro-MCA, Ser-MCA, Asn-MCA. Immunoreactivity of the antibody against the
      purified aminopeptidase was observed in human brain and most rat tissues examined
      including brain, liver, kidney, lung, heart, and skeletal muscle at the same
      molecular size as in bovine brain aminopeptidase. Most of the Lys-, Leu-, Met-,
      and Phe-MCA degrading activity in crude bovine and human brain extracts was
      absorbed by the aminopeptidase IgG, suggesting that this aminopeptidase is a
      major enzyme, sharing at least Lys-, Leu-, Met-, and Phe-MCA degrading
      aminopeptidase activities in the brains.

PMID- 8986640
TI  - Lung CuZn-superoxide dismutase and catalase gene expression in premature rabbits
      treated intratracheally with antioxidant-surfactant liposomes.
AB  - Tolerance to hyperoxia usually depends on an increase in lung antioxidant enzyme
      activity. Antioxidant-surfactant liposomes, encapsulating the antioxidant enzymes
      CuZn-superoxide dismutase (CuZnSOD) and catalase in synthetic surfactant lipids,
      increase lung antioxidant activity following intratracheal instillation in
      premature and term rabbits. We investigated whether the exogenous antioxidant
      enzymes encapsulated in these liposomes inhibit the endogenous antioxidant enzyme
      synthesis in the premature rabbit lung. Premature rabbits, delivered at 28 days
      of gestation, were treated intratracheally with antioxidant-surfactant liposomes,
      surfactant liposomes without antioxidant enzymes, or air placebo at birth and
      exposed to hyperoxia for 24 h. A comparison group was killed after breathing room
      air at birth. The right lungs of the pups were assayed for CuZnSOD and catalase
      activities and DNA content, the left lungs of the same pups were used to
      quantitate the concentrations of CuZnSOD and catalase mRNA using cRNA probes.
      Lung CuZnSOD and catalase mRNA quantities increased during exposure to hyperoxia,
      but were not affected by exogenous antioxidant enzymes. These data suggest that
      intratracheal instillation of CuZnSOD and catalase does not down-regulate mRNA
      transcription of these antioxidant enzymes in the premature rabbit lung.

PMID- 8986641
TI  - The development of insulin resistance with high fat feeding in rats does not
      involve either decreased insulin receptor tyrosine kinase activity or membrane
      glycoprotein PC-1.
AB  - Recent studies have suggested that the insulin receptor tyrosine kinase
      inhibitor, membrane glycoprotein PC-1, may play a role in certain insulin
      resistant states. In the present study, we examined whether either insulin
      receptor function or PC-1 activity was altered during the development of insulin
      resistance that occurs with high fat feeding in normal rats. Over the course of
      14 days of high fat feeding, both maximal and submaximal (physiological) insulin
      stimulated skeletal muscle glucose uptake decreased gradually; after 14 days of
      high fat feeding, submaximal and maximal insulin-stimulated glucose uptake
      decreased by approximately 40 and approximately 50%, respectively. In contrast,
      in the same muscles (tibialis anterior) of these animals, neither insulin
      receptor content nor insulin-stimulated insulin receptor autophosphorylation was
      altered after 14 days of high fat feeding. PC-1 has both nucleotide
      pyrophosphatase (EC 3.6.1.9) and alkaline phosphodiesterase I (EC 3.1.4.1) enzyme
      activities. These enzyme activities showed no changes during the course of 14
      days of high fat feeding. Individual data revealed that there was no significant
      correlation between insulin-stimulated glucose uptake and alkaline
      phosphodiesterase or nucleotide pyrophosphatase activity (P > 0.05). Together,
      these data indicate that neither defects in insulin receptor function nor
      elevated PC-1 activities are involved in the development of insulin resistance in
      rats with high fat feeding, and the insulin resistance induced with high fat
      feeding is likely due to postreceptor defects in skeletal muscle.

PMID- 8986642
TI  - Hexose metabolism in pancreatic islets: apparent dissociation between the
      secretory and metabolic effects of D-fructose.
AB  - In rat pancreatic islets, D-fructose causes a concentration-related shift to the
      left of the sigmoidal relationship between insulin release and D-glucose
      concentration. For instance, when D-fructose is tested at a 80 mM concentration,
      which is close to the threshold value for stimulation of insulin release by the
      ketohexose in the absence of D-glucose, a close-to-maximal secretory response is
      recorded in islets concomitantly exposed to as little as 6.0 to 8.3 mM D-glucose.
      Under these conditions, however, D-fructose fails to affect the utilization of D
      [5-3H]glucose, the oxidation of D-[U-14C]glucose, or its conversion to either 14C
      labeled acidic metabolites or amino acids. Under the same experimental
      conditions, the oxidation of D-[U-14C]fructose and its conversion to 14C-labeled
      amino acids represent no more than 80-85% of the corresponding values found with
      6 mM D-[U-14C]glucose. Actually, the total output of 14CO2 attributable to the
      oxidation of both D-[U-14C]glucose (6 mM) and D-[U-14C]fructose (80 mM) remains
      lower than that found in the sole presence of 8.3 mM D-[U-14C]glucose, despite
      the much higher rate of insulin secretion found in the former compared to the
      latter situation. These findings suggest that the insulinotropic action of D
      fructose cannot be fully accounted for by its capacity to act as a fuel in islet
      cells, as if it were to involve the generation of a second messenger distinct
      from those coupling factors currently implied in the process of nutrient
      stimulated insulin release.

PMID- 8986643
TI  - Immunodetection of mitochondrial glycerophosphate dehydrogenase (mGDH) by a
      polyclonal antibody raised against a recombinant mGDH fragment product.
AB  - The mitochondrial enzyme glycerophosphate dehydrogenase (mGDH) plays an essential
      role in the B-cell glucose-sensing device and its activity in islet homogenates
      is impaired in several animal models of type 2 diabetes. We have now developed a
      polyclonal antibody, raised against a recombinant mGDH fragment product, that
      could be used for the immunodetection of mGDH. Total RNA was isolated from rat
      pancreatic islets and used in the synthesis of cDNA. Specific primers were
      designed that corresponded to the FAD binding domain of mGDH. The PCR product was
      purified and cloned into an appropriate expression vector used for transformation
      of Escherichia coli cells. The fusion protein was extracted from the transformed
      cells, further purified, and used for immunization of rabbits. The antibody
      recognized a single band of 72 kDa in rat islets and testis. The recombinant mGDH
      product was also recognized as a single band with the expected 65-kDa reference.
      An ELISA procedure was designed for detection of antibodies against the
      recombinant mGDH fragment product. The availability of the mGDH antibody opens
      the way to a number of further applications such as immunocytochemis- try and
      mGDH quantification in biological material.

PMID- 8986644
TI  - Measurement of GLUT mRNA in liver of fetal and neonatal rats using a novel method
      of quantitative polymerase chain reaction.
AB  - Transfer of glucose into the hepatocyte is mediated by glucose transporters
      (GLUTs). GLUT mRNA levels are usually measured by Northern blot analysis. Reverse
      transcription-polymerase chain reaction (RT-PCR) is often used to measure RNA
      abundance. However, this method is only semiquantitative and has no internal
      control during first-strand synthesis. We designed a method of coreverse
      transcription and PCR amplification using bovine rhodopsin as an internal control
      for both cDNA synthesis and amplification. As part of the validation of this
      technique, we determined that there was no nonspecific amplification of bovine
      GLUTs by rhodopsin primers, that there were no differences in amplification due
      to different regions of the Glut gene amplified, and that there were no secondary
      structure effects on amplification. We applied our modified method of RT-PCR to
      measure the ontogeny of GLUT expression in liver of fetal and postnatal rats (d20
      fetuses and d1, d4, d14, and d21 juvenile rat pups). GLUT 1 mRNA quantity
      decreased whereas GLUT 2 increased with age. We were able to detect small
      quantities of GLUT 3 in fetal liver and of GLUT 5 in postnatal liver. This method
      of RT-PCR provides an internal control and allows measurement of mRNA levels in
      small quantities of tissue, making it ideal for use in the fetus and any system
      in which mRNA levels are low.

PMID- 8986645
TI  - Cathepsin K: isolation and characterization of the murine cDNA and genomic
      sequence, the homologue of the human pycnodysostosis gene.
AB  - Cathepsin K(EC 3.4.22.38) is a lysosomal cysteine protease that is strongly
      implicated in bone resorption. The human cathepsin K gene is highly expressed in
      osteoclasts and gene mutations cause pycnodysostosis, an autosomal recessive
      skeletal dysplasia. To investigate the evolutionary relatedness of cathepsin K
      across species, the mouse cathepsin K gene was isolated. A mouse heart cDNA
      clone, pMCatKl, contained the 3' untranslated region, mature enzyme coding
      sequence, and most of the propeptide. The remainder of the gene was amplified
      from mouse melanocyte RNA using 5' rapid amplification of cDNA ends. The gene
      contained a 990-bp open reading frame, predicting a 329-amino-acid
      prepropolypeptide. The structure of the protein included a 15-amino-acid
      presignal, a 99-amino-acid proregion, and a 215-amino-acid mature enzyme. Two
      potential N-glycosylation sites were identified, one in the proregion and one in
      the mature enzyme. The 5' untranslated region was 135 bp. The 3' untranslated
      region was 470 bp including a 9-bp poly(A) tract and contained two
      polyadenylation signals. The mouse cathepsin K nucleotide and amino acid
      sequences were highly conserved with the human, rabbit, and chicken homologues
      across the proregion and mature enzyme. The mouse cathepsin K gene was isolated
      from an V129 genomic library, and characterization of its genomic structure and
      intron sizes revealed exons with the initiation ATG in exon 2 and termination TGA
      in exon 8, a genomic organization that was highly conserved with its human
      homologue. The availability of the mouse cathepsin K cDNA and genomic sequences
      will facilitate generation of a mouse model of cathepsin K deficiency by gene
      targeting.

PMID- 8986646
TI  - Beta-sheet models for the ordered filamentous structure formed by a peptide that
      enhances the action of insulin.
AB  - Certain peptides with sequences related to part of the major histocompatibility
      complex class I antigen enhance the action of insulin. These peptides also
      aggregate into fibrous structures that seem to be related to their biological
      activity. In the current study, the 17-residue peptide with amino acid sequence
      Gly-Asn-Glu-Gln-Ser-Phe-Arg-Val-Asp-Leu-Arg-Thr-Leu-Leu-Arg-Tyr-Ala is used as a
      representative example of these bioactive molecules. As seen by electron
      microscopy, the peptide associates into gently twisted ribbons, 50 A thick, in
      which the amount of twist decreases as the ribbons become wider. X-ray
      diffraction analysis suggests that the peptides are arranged as in an
      antiparallel beta-sheet extending essentially endlessly along the fiber axis. The
      amino acid sequence of the peptide is such that one side of the beta-sheet is
      predominantly polar while the opposite side is nonpolar. This allows the beta
      sheets to form multilayers with alternating hydrophobic and hydrophilic
      interfaces. The length of the extended peptide (approximately 54 A) determines
      the thickness of the ribbon and the tendency of individual beta-sheets to twist
      accounts for the twisting of the ribbons. An alternative model is also discussed,
      again based on antiparallel beta-sheets, but with adjacent sheets interdigitated
      in a "side-by-side" fashion rather than forming stacked layers. Comparable
      inactive peptides such as Gly-Asn-Glu-Gln-Ser-Ala-Arg-Val-Asp-Leu-Arg-Thr-Leu-Leu
      Arg-Tyr-Tyr (changed amino acids underlined) do not form ordered filamentous
      structures.

PMID- 8986647
TI  - Maximum-entropy three-dimensional reconstruction with deconvolution of the
      contrast transfer function: a test application with adenovirus.
AB  - We have developed an objective, quantitative, and general algorithm to improve
      the fidelity of three-dimensional reconstructions made from electron micrographs
      while at the same time filtering much of the noise present in the recorded data.
      The new technique is called constrained maximum entropy tomography (COMET). The
      essence of the method is that it will produce the most featureless reconstruction
      that fits the projection data within their observational accuracy. In particular,
      the COMET procedure will minimise the detrimental effects of errors in the
      measured data and deconvolute the effects of the contrast transfer function. An
      objective test has been performed using COMET on a conventional image
      reconstruction obtained from cryo-electron micrographs of adenovirus. The density
      for hexon, the major coat protein of the virus, which is known to high resolution
      from X-ray crystallography, provided a known high-resolution control. The COMET
      reconstruction is in considerably better agreement with the crystallographic
      electron density than the original reconstruction, throughout the entire
      resolution range.

PMID- 8986648
TI  - Structural organization of the pre-mRNA splicing commitment: a hypothesis.
AB  - Several models have been presented in the past to explain localized distributions
      of nuclear RNAs from individual genes that range from small foci to more
      elongated "track-like" structures. We present here a hypothesis which explains
      that, in the case of regulated splicing, there is in diploid cells a spatial
      separation of transcription sites from the execution of regulated splicing which
      we situate to domains of SR protein accumulation. In addition, it explains the
      presence of poly(A) sequences, and the lack of the autoradiographic label due to
      short pulses of [3H]uridine, in these domains.

PMID- 8986649
TI  - The Cellulose System in the Cell Wall of Micrasterias
AB  - The cellulose system of the cell wall of Micrasterias denticulata and
      Micrasterias rotata was analyzed by diffraction contrast transmission electron
      microscopy, electron diffraction, and X-ray analysis. The studies, achieved on
      disencrusted cell ghosts, confirmed that the cellulose microfibrils occurred in
      crisscrossed bands consisting of a number of parallel ribbon-like microfibrils.
      The individual microfibrils had thicknesses of 5 nm for a width of around 20 nm,
      but in some instances, two or three microfibrils merged into one another to yield
      larger monocrystalline domains reaching up to 60 nm in lateral size. The
      orientation of the cellulose of Micrasterias is very unusual, as it was found
      that in the cell wall, the equatorial crystallographic planes of cellulose having
      a d-spacing of 0.60 nm [(11;0) in the Ibeta cellulose unit cell defined by
      Sugiyama et al., 1991, Macromolecules 24, 4168-4175] were oriented perpendicular
      to the cell wall surface. Up to now, such orientation has been found only in
      Spirogyra, another member of the Zygnemataceae group. The unusual structure of
      the secondary wall cellulose of Micrasterias may be tentatively correlated with
      the unique organization of the terminal complexes, which in this alga occur as
      hexagonal arrays of rosettes.

PMID- 8986651
TI  - Three-Dimensional Reconstruction of a Collagen IV Analogue in the Dogfish Egg
      Case Wall.
AB  - The wall of the egg case of the dogfish (Scyliorhinus canicula) contains an
      analogue of collagen Types IV and VIII organised into a regular 3-dimensional
      network. It presumably provides both a protective and a filtering role for the
      eggs contained within it. Electron micrographs of longitudinal and transverse
      sections, including systematically tilted sections, have been used both to
      define, for the first time, the space group symmetry of the lattice and to carry
      out 3-D reconstruction of the unit cell contents. This cell was found to be
      tetragonal, space group I422, with a = b = 11 &plusmn; 1 nm, and c = 74 &plusmn;
      4 nm. Consistent with this, projection symmetries were c2mm for the [1,0,0] view,
      p2mm for the [1,1,0] view, and p4mm for the projection down the c axis (the
      [0,0,1] view), and all observed reflections in the computed Fourier transform
      obeyed the rule h + k + l = 2n (n integer) for body-centred lattices. The 3-D
      reconstruction, the first electron micrograph 3-D reconstruction of a collagen
      containing material, is interpreted in terms of variations of previous molecular
      models for this structure. Type IV collagen is a constituent of the basal lamina,
      where it forms a network with both structural and filtering properties. The
      dogfish egg case structure may throw light on the (less regular) collagen IV
      structure of the basal lamina.

PMID- 8986650
TI  - Microstructures of external periosteal callus of repaired femoral fracture in
      children.
AB  - In order to understand further the mechanism of bone fracture repair, and thus to
      innovate better operative treatment for bone fracture and to design new implant
      materials for bone repair, microstructures of external periosteal callus (EPC) of
      repaired femoral fracture in both children and adults were investigated by using
      a scanning electron microscope, transmission electron microscopy, and an X-ray
      microdiffractometer. The repair time after the fractures in children and adults
      is on average 155 and 370 days, respectively. Collagen fibrils making up
      children's EPC (CEPC) are underdeveloped and insufficiently mineralized by
      hydroxyapatite (HA), while those from adults' EPC (AEPC) are similar to normal
      bone. A lot of particles loaded by brushite (DCPD) minerals were found among the
      collagen fibrils of CEPC. The main mineral phases in CEPC consist of DCPD and HA,
      while only HA exists in AEPC. Deposition of DCPD minerals could have compensated
      for the insufficient mineralization of the collagen fibrils of CEPC, thereby
      making fractured bone repair more rapidly in children than in adults.

PMID- 8986652
TI  - A structural study of isolated mammalian centrioles using negative staining
      electron microscopy.
AB  - We have used a combination of centrifugation onto electron microscope grids and
      negative staining to study the structure of isolated mammalian centrioles. The
      technique relies on visualisation of structural detail by use of a
      goldthioglucose negative stain. The approach provides an easy structural
      definition of the mature and immature centriole and has revealed some novel
      proximal projections on the mature centriole. The rapid technique should prove of
      use in future analyses of centriolar structure and biochemistry.

PMID- 8986653
TI  - Immunogold localisation of the intermediate chain within the protein complex of
      cytoplasmic dynein.
AB  - It was our goal to determine the location of the intermediate chain within the
      complex of cytoplasmic dynein by immunoelectron microscopy. To do so we generated
      two monoclonal antibodies (m74-1 and m74-2) specific for the intermediate chain.
      Both antibodies recognised the intermediate chain by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis immunoblot and ELISA assays of native and
      denatured proteins. When sucrose density gradient-purified cytoplasmic dynein
      from bovine brain was incubated with the gold-conjugated monoclonal antibodies,
      m74-1 and m74-2, and examined by negative staining, the gold label was found
      opposite the globular heads at the base of the V-shaped stalk of the motor
      complex. The labelling of the intermediate chain is the first mapping of a
      component within cytoplasmic dynein. The identification of the intermediate chain
      at the base of the complex supports a possible docking function of the
      intermediate chain.

PMID- 8986654
TI  - Two-dimensional crystallization of brush border myosin I.
AB  - Brush border myosin-I (BBMI) is a single-headed unconventional myosin found in
      the microvilli of intestinal epithelial cells, where it links the core bundle of
      actin filaments to the plasma membrane. An association of BBMI with anionic
      phospholipids has been shown to be mediated by a carboxy-terminal domain which is
      rich in basic amino acids. We have exploited this natural affinity of BBMI for
      negatively charged lipids to form two-dimensional (2D) crystals of this protein
      which are suitable for structural analysis by electron crystallographic
      techniques. The 2D crystals which we have obtained belong to one of two space
      groups, p22121 or p2. We present here projection maps calculated from images of
      negatively stained crystals for each of these crystal types to a resolution of 20
      A and show that the asymmetric unit is the same in both crystal types.

PMID- 8986655
TI  - Use of the hepatitis-B vaccine and infection with hepatitis B and C among
      orthopaedic surgeons. The American Academy of Orthopaedic Surgeons Serosurvey
      Study Committee.
AB  - We used a questionnaire, with a guarantee of anonymity to the respondents, and
      conducted serological testing of 3411 attendees at the 1991 Annual Meeting of The
      American Academy of Orthopaedic Surgeons to evaluate the prevalences of infection
      with the hepatitis-B and C viruses and the use of the hepatitis-B vaccine among
      orthopaedic surgeons. There was evidence of infection with hepatitis B in 410 (13
      per cent) of 3239 participants who had reported having no non-occupational risk
      factors; 2103 (65 per cent) reported that they had been immunized with the
      hepatitis-B vaccine. Of 3262 participants who reported having no non-occupational
      risk factors and who were evaluated for infection with hepatitis C, twenty-seven
      (less than 1 per cent) tested positive for the antibody to the hepatitis-C virus.
      The prevalence of previous infection with hepatitis B increased with increasing
      age; four (3 per cent) of 136 surgeons who were twenty to twenty-nine years old
      had evidence of infection, whereas ninety-six (27 per cent) of 360 surgeons who
      were sixty years old or more had evidence of infection. The prevalence of
      infection with hepatitis C also increased with increasing age; none of 135
      surgeons who were twenty to twenty-nine years old had evidence of infection, and
      five (1 per cent) of 360 surgeons who were sixty years old or more had evidence
      of the virus. The prevalence of vaccination decreased steadily with age: 123 (90
      per cent) of 136 surgeons who were twenty to twenty-nine years old reported that
      they had received the hepatitis-B vaccine, whereas 127 (35 per cent) of 360
      surgeons who were sixty years old or more reported that they had received the
      vaccine. The prevalence of infection with hepatitis B or hepatitis C was not
      associated with the measured indices of exposure to the blood of patients (the
      number of cutaneous or mucosal contacts with blood that had occurred within the
      previous month or the number of percutaneous injuries that had occurred within
      the previous month or year, as recalled by the participants). In conclusion, the
      prevalence of immunization with the hepatitis-B vaccine was high among the
      orthopaedic surgeons studied. Although the prevalence of infection with the
      hepatitis-C virus was several times greater in the current investigation than has
      been reported in studies of blood donors in the United States, infection with
      this virus was not associated with the indices of occupational exposure to blood
      measured in this study.

PMID- 8986656
TI  - An arthroscopic technique for anterior stabilization of the shoulder with a
      bioabsorbable tack.
AB  - Arthroscopically assisted repair of the anterior aspect of the labrum with use of
      a bioabsorbable tack was performed in fifty-two consecutive patients who had
      chronic anterior instability of the shoulder. The average age of the patients was
      twenty-eight years (range, sixteen to fifty years). The etiology of the
      instability was a traumatic injury in forty-nine patients; twenty-six of those
      injuries were sustained during participation in a contact sport. Fifty shoulders
      had a Bankart lesion. The patients were evaluated at an average of forty-two
      months (range, twenty-four to sixty months) after the procedure. Forty-one (79
      per cent) of the patients were asymptomatic and were able to participate in
      sports without restriction. The repair was considered to have failed in eleven
      (21 per cent) of the patients. In four of them, the failure resulted from a
      single traumatic reinjury during participation in a contact sport, and three of
      these reinjuries were treated nonoperatively. The remaining seven failures
      occurred atraumatically. Eight patients had an open glenoid-based capsulorrhaphy
      as a consequence of recurrent instability. At the reoperation, no evidence of the
      tack was found in any patient. In seven patients, the Bankart lesion had
      completely healed, and the anteroinferior aspect of the capsule was patulous.
      Anterior stabilization of the shoulder with a bioabsorbable tack may be indicated
      for patients who have anterior instability but do not need a capsulorrhaphy or
      capsular imbrication to reduce the joint volume.

PMID- 8986657
TI  - Arthroscopic release for chronic, refractory adhesive capsulitis of the shoulder.
AB  - Idiopathic adhesive capsulitis usually responds to gentle physical therapy or, if
      that fails, to closed manipulation with the patient under anesthesia. In some
      patients, however, loss of motion may be refractory to either of these treatments
      and an operative release may be indicated. We are reporting on the technique and
      results of arthroscopic capsular release as a new alternative for the management
      of such patients. During a three-year period, we managed twenty-three patients
      who had idiopathic adhesive capsulitis that had failed to respond to physical
      therapy or closed manipulation. These patients had an arthroscopic anterior
      capsular release and received forty-eight hours of intensive physical therapy as
      inpatients. During the physical therapy, the patients received an interscalene
      regional analgesic with use of repeated nerve blocks or with a continuous
      infusion through an interscalene catheter. This was followed by a supervised
      outpatient physical-therapy program. Six patients also had an arthroscopic
      acromioplasty for the treatment of impingement. There were no complications
      related to any of the procedures. At a mean of thirty-nine months (range, twenty
      four to sixty-four months) after the arthroscopic procedure, the improvement in
      the score of Constant and Murley averaged 48 points (range, 13 to 77 points). The
      mean improvement in motion was 49 degrees (range, 0 to 105 degrees) for flexion;
      42 degrees (range, 10 to 80 degrees) and 53 degrees (range, 0 to 100 degrees) for
      external rotation in adduction and abduction, respectively; and eight spinous
      process levels (range, three to fourteen levels) and 33 degrees (range, 30 to 60
      degrees) for internal rotation in adduction and abduction, respectively. These
      gains in motion were all significant (p < 0.01) compared with the preoperative
      values and were within a mean of 7 degrees of the values for the contralateral,
      normal shoulder. We concluded that, in patients who have loss of motion that is
      refractory to closed manipulation, arthroscopic capsular release improves motion
      reliably with little operative morbidity.

PMID- 8986658
TI  - Operative treatment of volar intra-articular fractures of the distal end of the
      radius.
AB  - We retrospectively reviewed the results of operative treatment of forty-nine
      volar marginal intra-articular fractures of the distal end of the radius.
      According to the Comprehensive Classification of Fractures, there were two B3.1
      fractures (characterized by a small volar fragment, with the sigmoid notch
      intact), three B3.2 fractures (characterized by a large volar fragment that
      included the sigmoid notch), and forty-four B3.3 fractures (characterized by
      comminution of the volar fragment). Although all fractures healed and only nine
      patients had evidence of osteoarthrosis on follow-up radiographs, there were six
      early and fourteen late complications, some of which adversely influenced the
      over-all outcome. After an average of fifty-one months (range, twenty-four to 117
      months), there were thirty-one excellent, ten good, and eight fair results
      according to the system described by Gartland and Werley, and thirty-two
      excellent, nine good, five fair, and three poor results according to the modified
      system of Green and O'Brien. Two factors were found to have a significant
      association with a fair or poor outcome: evidence of osteoarthrosis on the most
      recent follow-up radiographs and reversal of the normal volar tilt of the distal
      end of the radius. The age of the patient, the interval from the injury to the
      operation, a concomitant injury of the ipsilateral upper extremity, an associated
      fracture of the ulnar styloid process, the radio-ulnar index, ulnar angulation,
      the classification of the fracture, comminution of the volar fragment, and
      articular incongruity were not significantly associated with the outcome.

PMID- 8986659
TI  - Non-union of the scaphoid. Treatment with cannulated screws compared with
      treatment with Herbert screws.
AB  - We retrospectively reviewed the results for thirty-four patients in whom a non
      union of the scaphoid had been treated with bone-grafting and internal fixation
      with use of one of two types of screws as well as the temporary placement of
      Kirschner wires parallel to the screw to prevent rotation. The patients were
      divided into two groups: Group 1 contained sixteen patients who had been managed
      with a Herbert screw from 1986 through 1989 and Group 2, eighteen patients who
      had been managed with a 3.5-millimeter cannulated AO/ASIF screw from 1990 through
      1992. There were no clinical or radiographic differences between the two groups.
      The time to union, confirmed with tomography, was 7.6 +/- 3.6 months for Group 1
      and 3.6 +/- 1.2 months for Group 2. This difference was significant (p < 0.01).
      Both screws significantly improved the alignment of the scaphoid and decreased
      carpal collapse (p < 0.05). Regardless of the type of screw used, the time to
      union was significantly shorter when the screw had been placed in the central one
      third of the scaphoid (p < 0.05). Seventeen of the eighteen cannulated screws had
      been placed centrally, compared with seven of the sixteen Herbert screws (p <
      0.01).

PMID- 8986660
TI  - Carpal instability in the weight-bearing upper extremity.
AB  - The prevalence of carpal instability in a paraplegic population was investigated
      to establish an association between chronic repetitive stress on the wrist and
      the development of such instability. Nine of 162 paraplegic patients had static
      carpal instability and no history of an acute injury of the wrist. The
      predominant pattern of instability, found in eleven wrists (six patients), was
      non-dissociative volar intercalated segmental instability. The prevalence of
      carpal instability increased with the duration of weight-bearing on the upper
      extremity. Eighteen per cent of the patients in whom the spinal cord injury had
      occurred more than twenty years before the study had carpal instability. Carpal
      instability in these weight-bearing upper extremities and the increase in its
      prevalence with the duration of the forces across the wrist demonstrate an
      association between chronic repetitive stress on the wrist and carpal
      instability.

PMID- 8986661
TI  - Evaluation of a program for long-term treatment of Duchenne muscular dystrophy.
      Experience at the University Hospitals of Cleveland.
AB  - One hundred and forty-four boys who had Duchenne muscular dystrophy were managed
      at a single center between 1953 and 1994 and were followed for a mean of 8.9
      years. The long duration of follow-up provided an opportunity to examine the
      effects of physical therapy and orthopaedic treatment on contractures of the
      lower extremities and on the duration of the ability to walk. Contractures of the
      lower extremities were controlled best when patients were managed with a
      combination of daily passive stretching exercises, prescribed periods of standing
      and walking, tenotomy of the Achilles tendon, posterior tibial-tendon transfer,
      and application of knee-ankle-foot orthoses. Approximately two years after
      bracing, the severity of the contracture of the heel cords was similar in the
      patients who had had an operation and those who had not. By the fourth year after
      bracing, however, the patients who had had an operation had less severe
      contractures than those who had had bracing alone. Five to seven years after the
      operation and bracing, control of contractures was still good, especially for the
      patients who had had posterior tibial-tendon transfer. Contracture of the knee
      was well controlled five to seven years after bracing in all patients who had had
      bracing, with or without an operation. The program enabled the patients who had
      been managed with bracing to walk until a mean age of 13.6 years. After loss of
      the ability to walk with bracing, the ability to stand continued for an
      additional two years with use of orthoses. The findings of the present study
      demonstrate the value of traditional methods of operative treatment and bracing
      for controlling contractures of the lower extremities in patients who have
      Duchenne muscular dystrophy and for prolonging their ability to walk.

PMID- 8986662
TI  - Revision of the acetabular component of a total hip arthroplasty with cement in
      young patients without rheumatoid arthritis.
AB  - The results for eighty-two young patients without rheumatoid arthritis who had
      had eighty-seven revisions of the acetabular component because of aseptic
      loosening were studied. The mean duration of follow-up was approximately six
      years (range, 1.9 to 18.1 years). The clinical result was excellent or
      satisfactory for seventy-nine hips (91 per cent). However, at the latest
      radiographic assessment, twenty-six sockets were loose. Of the fifty hips that
      had had good bone stock (only slight enlargement of the acetabulum or local
      defects involving only one wall) before the revision, seven (14 per cent) had
      loosening of the socket, compared with nineteen (51 per cent) of the thirty-seven
      that had had poor bone stock (massive or global collapse of the acetabulum and
      defects involving at least two walls). The relationship between loosening and the
      quality of the bone stock before the revision was highly significant (p = 0.0002,
      chi-square test). The results of revision of the socket with use of cement and
      without use of any bone grafts in young patients who have poor acetabular bone
      stock are not very encouraging. The need for regular follow-up of all patients
      who have had an arthroplasty cannot be overemphasized.

PMID- 8986663
TI  - Energy expenditure during walking by children who have proximal femoral focal
      deficiency.
AB  - The energy expended during walking by sixteen children who had proximal femoral
      focal deficiency was measured to compare the outcomes after Syme amputation
      (seven subjects) with those after Van Nes rotational osteotomy (nine subjects).
      Multivariate regression analysis revealed that the subjects who had had a Van Nes
      procedure had a mean oxygen cost (energy per unit of body mass expended per
      distance walked) that was 0.12 milliliter per kilogram of body mass per meter
      lower than that of the subjects who had had a Syme amputation (p = 0.001). The
      subjects who had had a Van Nes procedure tended to walk faster (p = 0.07). A
      significant decrease in the oxygen cost as a function of increasing age was
      observed for both groups (p < 0.0001, r2= 0.79). We believe that the reduced
      energy expenditure associated with the Van Nes rotational osteotomy is one of
      several factors to consider when deciding which operation should be done for
      children who have proximal femoral focal deficiency.

PMID- 8986664
TI  - Pemberton pelvic osteotomy and varus rotational osteotomy in the treatment of
      acetabular dysplasia in patients who have static encephalopathy.
AB  - Forty-four patients (fifty-two hips) who had static encephalopathy and acetabular
      dysplasia were managed with a Pemberton osteotomy as part of a comprehensive
      operative approach. Thirty-three patients had quadriplegia and were unable to
      walk; the remaining eleven patients had diplegia and could walk. The age at the
      time of the operation ranged from four years and five months to sixteen years and
      five months, as an open triradiate cartilage is a prerequisite for the Pemberton
      procedure. Concomitant operative procedures included a varus rotational osteotomy
      in fifty of the involved hips, a soft-tissue release in thirty-seven hips, and an
      open reduction in thirteen hips. The mean center-edge angle preoperatively was 
      11 degrees (range, -80 to 17 degrees), which improved to a mean of 27 degrees
      (range, 5 to 62 degrees) at the time of the latest follow-up. The mean duration
      of follow-up was four years (range, two years to eight years and eight months).
      At the time of writing, none of the hips had redislocated but one hip had
      subluxated. Eight of the hips had been painful preoperatively, but none of these
      was painful at the time of the most recent follow-up. One patient who had not had
      pain in the hip preoperatively had pain at the time of the follow-up evaluation.
      There were no complications attributable to posterior uncovering of the hip. The
      age of the patient at the time of the operation had no discernible effect on the
      result.

PMID- 8986665
TI  - Limb salvage for neoplasms of the shoulder girdle. Intermediate reconstructive
      and functional results.
AB  - The intermediate functional results were assessed for fifty-seven patients who
      had had a limb-salvage procedure for treatment of a tumor of the shoulder girdle
      region at our institution from 1980 through 1990. Fifty-three patients had a
      malignant bone tumor (a sarcoma) and four had an extensive giant-cell tumor. The
      resections were classified according to the system of the Musculoskeletal Tumor
      Society. A variety of reconstructive procedures were performed after resection of
      the tumor, with the choice of procedure depending on the type of resection and
      the needs of the patient. The functional results were described and graded
      quantitatively according to the functional rating system of the Musculoskeletal
      Tumor Society. The average duration of follow-up was 5.3 years (median, 4.6
      years) for the forty-seven patients who were still alive at the time of the
      latest follow-up examination. Eight patients died of disease and two others died
      of unrelated malignant tumors an average of 1.8 years postoperatively. The
      resection of the tumor was classified as wide in forty of the fifty-three
      patients who had a sarcoma and as marginal in thirteen; four patients had local
      recurrence (two, after a wide resection, and two, after a marginal resection).
      One of the four patients who had a giant-cell tumor had local recurrence. The
      functional results were related to the type of resection and the method of
      skeletal reconstruction. After resection of the entire scapula and the proximal
      aspect of the humerus, reconstruction with a spacer frequently resulted in
      asymptomatic superior subluxation of the implant and poor function of the
      shoulder. After extra-articular resection of the glenoid cavity and the proximal
      aspect of the humerus with loss of the abductor mechanism, osseous arthrodesis
      resulted in good function that was superior to that found after reconstruction
      with a spacer or a proximal humeral replacement prosthesis. Our preferred method
      to achieve fusion was insertion of an intercalary allograft and a vascularized
      fibular graft. However, the allograft fractured in three of four patients in whom
      primary fusion had been obtained with this technique. An osteoarticular allograft
      inserted after intra-articular resection of the proximal aspect of the humerus
      and preservation of the abductor mechanism provided good function that was
      superior to that found after reconstruction with a proximal humeral replacement
      prosthesis, which produced symptomatic instability that led to a secondary
      arthrodesis in some patients. However, subchondral fracture and collapse of the
      osteoarticular allograft occurred in four of eight patients by the time of the
      latest follow-up examination. The results of all methods of reconstruction were
      satisfactory with regard to pain, emotional acceptance, and manual dexterity. We
      believe that the use of a method of reconstruction that is appropriate with
      regard to the needs of the patient and preoperative counseling regarding the
      expected functional level and restrictions of activity are critical for a high
      level of postoperative satisfaction.

PMID- 8986666
TI  - Transfer of a severely damaged digit to reconstruct an amputated thumb.
AB  - We retrospectively reviewed the results of reconstruction of a traumatically
      amputated thumb with use of an adjacent severely damaged digit in twenty-seven
      patients (twenty-five male and two female patients). The mean duration of follow
      up was nine years (range, two to twenty-one years). The mean age at the time of
      the reconstruction was thirty-four years (range, thirteen to fifty-six years).
      Five patients had the reconstruction on the day of the injury and twenty-two,
      after a mean delay of five months (range, fifteen days to thirteen months).
      Segments of the index finger were used in twenty-two patients; of the long
      finger, in four patients; and of the ring finger, in one patient. There were four
      complications: necrosis of the dorsal skin in one patient, reflex sympathetic
      dystrophy in one patient, and contracture of the first web space in two patients.
      Discriminative sensibility was ten millimeters or less, according to the Weber
      test, in twenty-four thumbs. Cortical integration with reference to the recipient
      thumb, on stimulation of the pollicized segment, was good in ten patients. Eleven
      patients could achieve tip-to-tip contact between the thumb and the little finger
      and twenty-five patients, between the thumb and the most radial finger. The
      ability to perform activities of daily living was considered good for ten
      patients, fair for eleven, and poor for six. Only digits with a nail, either
      present on the transferred segment or as a result of a free vascularized nail
      transfer, were considered to have a good cosmetic result. Although these results
      are far from impressive, the reconstruction is a viable alternative for selected
      patients because it maintains the ability to grasp objects and to oppose the
      digits.

PMID- 8986668
TI  - Leiomyoma of the hand in a child who has the human immunodeficiency virus.

PMID- 8986667
TI  - Excursion and strain of the median nerve.
AB  - Five fresh-frozen transthoracic cadaver specimens (ten upper extremities) were
      dissected in order to measure excursion and strain of the median nerve at the
      wrist and the elbow in association with different positions of the shoulder,
      elbow, wrist, and fingers. The relationships between motions of the joints and
      excursion and strain at the wrist and the elbow as well as between excursion and
      strain were also determined. When the wrist was moved from 60 degrees of
      extension to 65 degrees of flexion, the median nerve at the wrist underwent a
      mean total excursion of 19.6 millimeters (9.2 +/- 1.38 millimeters [mean and
      standard deviation] in extension and 10.4 +/- 1.50 millimeters in flexion). The
      change in strain was not measurable secondary to nerve-wrinkling. Motion of the
      fingers from hyperextension to full flexion caused a mean total excursion of 9.7
      millimeters (6.3 +/- 1.31 millimeters in hyperextension and 3.4 +/- 1.04
      millimeters in flexion) and a change in strain of 19.0 per cent. This change in
      strain became more pronounced when the wrist and the fingers moved in synergy.
      Such strain, if constant, has been shown to decrease microvascular perfusion and
      nerve conduction in rabbits. With motion of the shoulder, the mean total
      excursion of the median nerve at the elbow was 9.1 millimeters (4.4 +/- 1.64
      millimeters in abduction and 4.7 +/- 1.81 millimeters in adduction) and the
      change in strain was 13.3 per cent. With motion of the elbow, the mean total
      excursion was 12.3 millimeters (12.3 +/- 4.20 millimeters in flexion and zero
      millimeters in the resting position) and the change in strain was not measurable
      because of the wrinkle effect in flexion. With motion of the wrist, the mean
      total excursion was 5.6 millimeters (4.3 +/- 1.95 millimeters in extension and
      1.25 +/- 0.81 millimeters in flexion) and the change in strain was 14.8 per cent.
      With motion of the fingers, the mean total, excursion was 3.4 millimeters (2.6 +/
      1.13 millimeters in hyperextension and 0.80 +/- 0.92 millimeter in flexion) and
      the change in strain was 10.3 per cent. Motion of the wrist and the fingers
      induced profound excursion of the median nerve at the wrist, whereas motion of
      the shoulder and the elbow induced marked excursion of the median nerve at the
      elbow. These excursions were much more pronounced when a number of joints were
      moved in a composite manner. Any factor that might limit normal excursion, such
      as scarring, could induce strains that could adversely affect the function of the
      median nerve. The finding that the position and movement of the limb had a
      profound effect on excursion and strain of the median nerve at the wrist and the
      elbow may aid in the understanding of the pathophysiology of median-nerve
      neuropathy.

PMID- 8986669
TI  - Trans-scaphoid, transtriquetral, volar lunate fracture-dislocation of the wrist.

PMID- 8986670
TI  - Compression of the spinal cord due to destructive spondyloarthropathy of the
      atlanto-axial joints.

PMID- 8986671
TI  - The threadwire saw: a new device for cutting bone.

PMID- 8986672
TI  - Total hip arthroplasty with hydroxyapatite-coated prostheses.

PMID- 8986673
TI  - Formation of the pelvis by membranous instead of endochondral ossification?

PMID- 8986675
TI  - There's a hole in my bucket: the cost of disposable instruments.

PMID- 8986674
TI  - New developments in topical estrogen therapy.
AB  - OBJECTIVE: To review new developments in transdermal E2 therapy in postmenopausal
      women. DESIGN: A bibliographic search (Medline) of the medical literature from
      1966 through 1995 was used to identify new studies evaluating transdermal E2.
      PATIENT(S): Menopausal and postmenopausal women. RESULT(S): Like oral estrogen,
      transdermal E2 relieves menopausal symptoms, reverses urogenital atrophy, and
      conserves bone economy. Initial studies have demonstrated beneficial effects of
      transdermal E2 on cardiovascular function. Quality of life, patient satisfaction,
      and compliance also improve with transdermal E2. Advances in transdermal delivery
      continue to emerge, including low-dose systems and patches that maintain serum E2
      levels for a full 7-day period. CONCLUSION(S): New developments in transdermal
      administration have the potential to increase the number of postmenopausal women
      who accept and are compliant with long-term estrogen replacement therapy.

PMID- 8986676
TI  - Antoine van Leeuwenhoek and the discovery of sperm.

PMID- 8986677
TI  - Fertility outcome after laparoscopic microsurgical tubal anastomosis.
AB  - OBJECTIVE: To evaluate fertility outcome after laparoscopic microsurgical tubal
      anastomosis. DESIGN: A retrospective study. SETTING: Infertility Medical Center
      affiliated with University Medical School. PATIENT(S): Fifty-four patients, who
      had previously undergone tubal sterilization, seeking reversal. INTERVENTION(S):
      Laparoscopic microsurgical tubal anastomosis was performed. MAIN OUTCOME
      MEASURE(S): Pregnancy success was assessed. RESULT(S): The overall pregnancy rate
      (PR) was 77.5% (38/49) and 29 patients already have delivered healthy offspring.
      Pregnancy in seven patients is ongoing and one case ended in abortion. There was
      one case of ectopic pregnancy. The pregnancy success according to the method of
      previous tubal sterilization was 16 of 24 with the Fallope-ring method, 14 of 15
      in cases of cauterization, and 8 of 10 in patients in whom the Pomeroy technique
      was used. The pregnancy success according to the site of anastomosis was 3 of 4
      in cornual-isthmic, 4 of 5 in isthmic-isthmic, 26 of 35 in isthmic-ampulla, 3 of
      3 in cornual-ampulla, and 2 of 2 in ampulla-ampulla. The pregnancy success
      according to the tubal length was 5 of 7 at a length < or = 4 cm, 3 of 5 at 5 cm,
      15 of 17 at 6 cm, and 15 of 20 at lengths > or = 7 cm. CONCLUSION(S): Considering
      the high PR in our minimal follow-up period of 12 months, laparoscopic
      microsurgical tubal anastomosis could be an alternative procedure to
      microsurgical laparotomy in patients requesting reversal of tubal sterilization.

PMID- 8986678
TI  - A randomized clinical trial of oxidized regenerated cellulose adhesion barrier
      (Interceed, TC7) alone or in combination with heparin.
AB  - OBJECTIVE: To compare the efficacy of heparin-saturated oxidized regenerated
      cellulose absorbable adhesion barrier, Interceed (TC7; Johnson and Johnson
      Medical Inc., New Brunswick, NJ) to oxidized regenerated cellulose alone for the
      prevention of postoperative adhesions. DESIGN: Clinical trial. By random
      assignment, one ovary was wrapped in oxidized regenerated cellulose, and the
      contralateral ovary was wrapped in oxidized regenerated cellulose saturated with
      a heparin solution (1,000 U/mL). PATIENT(S): Forty women with defects on both
      ovaries due to adhesiolysis and/or ovarian cystectomy. MAIN OUTCOME MEASURE:
      Adhesion formation and raw ovarian surface area were assessed at second-look
      laparoscopy 10 days to 16 weeks later. RESULT(S): At the second-look laparascopy
      adhesions were present on 52.5% (21/40) of the ovaries treated with oxidized
      regenerated cellulose plus heparin and in 65% (26/40) of the contralateral
      ovaries treated with oxidized regenerated cellulose alone. For ovaries treated
      with oxidized regenerated cellulose plus heparin, the raw surface area was
      reduced from 9.41 +/- 1.27 cm2 (mean +/- SE) at laparotomy to 1.33 +/- 0.52 cm2
      at second-look laparoscopy. The corresponding figures for ovaries treated with
      oxidized regenerated cellulose alone were from 10.24 +/- 1.08 to 1.92 +/- 0.54
      cm2, respectively. The mean difference between the reductions in raw surface area
      (85.9% for oxidized regenerated cellulose plus heparin; 81.3% for oxidized
      regenerated cellulose alone) was not significantly different from zero
      (difference = - 0.24 cm2; 95% confidence interval = -2.56 to 3.04).
      CONCLUSION(S): Adding heparin did not enhance significantly the adhesion-reducing
      capacity of oxidized regenerated cellulose adhesion barrier when applied to
      ovarian surfaces after cystectomy and/or ovariolysis at laparotomy. This
      conclusion is subject to the possibility of a type II error.

PMID- 8986679
TI  - Multifetal reduction increases the risk of preterm delivery and fetal growth
      restriction in twins: a case-control study.
AB  - OBJECTIVE: To compare pregnancy outcome in twin gestations resulting from
      multifetal reduction to "primary" twin pregnancies derived from either
      spontaneous conception or infertility therapy. DESIGN: Case-control study.
      SETTING: University-affiliated tertiary center. PATIENT(S): Multifetal
      pregnancies (quadruplets or more) reduced to twins (group A) compared with twin
      gestations conceived either spontaneously (group B) or through infertility
      therapy (group C). INTERVENTION(S): Multifetal reduction for group A; perinatal
      care for groups A, B, and C. MAIN OUTCOME MEASURE(S): Comparison of perinatal
      complications between groups including antepartum bleeding, premature membrane
      rupture, and preterm labor. Neonatal outcomes compared including gestational age
      at delivery, birth weight, incidence of fetal growth restriction, and twin
      discordancy. RESULT(S): A higher incidence of idiopathic preterm labor was noted
      in group A cases (14/18) compared with either of the control groups (B: 26/54, or
      C: 24/54). As a consequence, group A had the lowest gestational age at delivery
      (32.6 +/- 3.9 weeks) compared with groups B (33.6 +/- 4.4 weeks) and C (36.0 +/-
      3.4 weeks). Corresponding birth weights of both first- and second-born twins were
      significantly lower in group A compared with group C, whereas the birth weight
      comparison between groups A and B showed a nonsignificant difference. The
      proportion of pregnancies in which one or both twins weighted less than the 10th
      percentile was greatest in group A pregnancies (A: 5/18 versus C: 5/54).
      Discordant birth weight among twin pairs was proportionately greater for group A
      cases at both the 20% and 30% discordance levels. CONCLUSION(S): Twin gestations
      resulting from multifetal reduction are at increased risk for preterm birth,
      fetal growth restriction, and discordancy when compared with fertility therapy
      derived, nonreduced twins.

PMID- 8986680
TI  - Somatostatin treatment reduces the exaggerated response of adrenocorticotropin
      hormone and cortisol to corticotropin-releasing hormone in polycystic ovary
      syndrome.
AB  - OBJECTIVE: To evaluate the influence of somatostatin analogue (octreotide) in the
      function of hypothalamic-pituitary-adrenal (HPA) axis in women with polycystic
      ovary syndrome (PCOS). SETTING: Women referred to the Department of Obstetrics
      and Gynecology, Universita Cattolica del Sacro Cuore. PATIENT(S): Twelve PCOS
      women and 12 normo-ovulatory controls. INTERVENTION(S): In early follicular
      phase, I microgram/kg human corticotrophin-releasing hormone (CRH) was injected
      at 9:00 A.M. and blood samples were collected for 90 minutes after stimulus; ACTH
      and cortisol plasma levels were measured. The following day at 8:00 A.M., PCOS
      patients received an ACTH test (250 micrograms IV) and samples were collected 60
      minutes after injection. After 6 weeks of octreotide treatment (100 mg s.c. twice
      daily), PCOS patients repeated the same study. MAIN OUTCOME MEASURE(S): Plasma
      cortisol and ACTH concentrations. RESULT(S): The ACTH and cortisol baseline
      levels were similar in PCOS and control patients. The responses to human CRH of
      ACTH (incremental area = 437.86 +/- 188.7 versus 175.78 +/- 87.6 pmol/L; mean +/-
      SD) and cortisol (incremental area = 17,293.6 +/- 4,320.3 versus 5,885 (912.1
      nmol/L) were significantly greater in PCOS with respect to control subjects.
      After octreotide treatment, ACTH response significantly decreased and no
      difference was observed with respect to controls (incremental area = 176.94 +/-
      91.4). Cortisol responses were decreased by treatment. However, they remained
      significantly higher than in controls. Treatment did not modify adrenal response
      to IV ACTH. CONCLUSION(S): Data suggest that, in the HPA axis, hyperfunction of
      PCOS somatostatin could be involved partially.

PMID- 8986681
TI  - Effectiveness of tibolone on hypoestrogenic symptoms induced by goserelin
      treatment in patients with endometriosis.
AB  - OBJECTIVE: To investigate the efficacy and safety of tibolone on hypoestrogenic
      vasomotor symptoms and bone parameters in patients treated with goserelin
      acetate. DESIGN: Prospective, randomized placebo controlled double-blind study.
      SETTING: Human volunteers in a university-based fertility clinic. PATIENT(S):
      Twenty-nine women of mean age 29.2 +/- 4.8 years with mild to severe
      endometriosis undergoing 6 months of treatment with 3.6 mg goserelin acetate in
      an SC depot formulation were studied. INTERVENTION(S): The patients were
      allocated randomly to either 2.5 mg/d tibolone (n = 15) or an iron pill (n = 14)
      in a double-blinded fashion beginning in the third cycle. MAIN OUTCOME
      MEASURE(S): Frequency and severity of hot flushes, sweating, irritability, loss
      of libido, nervousness, and sleeplessness were assessed by the patients using 0
      to 6 point scoring system and compared. Samples of urine were obtained for
      calcium and creatinine (Ca:Cr) ratios at the start of treatment and monthly there
      after. The vasomotor scoring for each symptom and Ca:Cr ratios before the
      treatment and at the end of 6th month were analyzed by parametric and
      nonparametric tests. RESULT(S): The mean age, weight, vasomotor scores, pelvic
      scores, and urine Ca:Cr ratios were similar in both placebo and tibolone group
      (28.7 +/- 4.8 versus 27.6 +/- 6.3 years, 50.9 +/- 5.3 versus 53.1 +/- 7.1 kg, 4.7
      +/- 1.1 versus 4.2 +/- 0.8, and 0.056 +/- 0.008 versus 0.059 +/- 0.006,
      respectively). The decreases in vasomotor scoring as regards to hot flushing,
      sweating, and other associated symptoms were statistically significant in
      tibolone group compared with placebo (10.4 +/- 1.6 versus 24.6 +/- 4.9). During
      the study significant reductions in urine Ca:Cr ratio was obtained in the
      tibolone patients compared with placebo (0.031 +/- 0.006 versus 0.0055 +/-
      0.007). The incidence of side effects (weight change, vaginal bleeding) was low
      and did not differ from the placebo group. CONCLUSION(S): Considering the
      beneficial effects of tibolone on vasomotor symptoms and bone loss, our data
      suggest that this synthetic steroid is an effective and safe option in relieving
      symptoms induced by GnRH-analogue.

PMID- 8986682
TI  - Potential effects of midcycle cervical mucus on mediators of immune reactivity.
AB  - OBJECTIVE: To examine the effect of cervical mucus (CM) on immune mediators in
      cervicovaginal lavage fluid. DESIGN: The stability of cytokines and
      immunoglobulins (Ig) within cervicovaginal lavage fluid was determined during 18
      hour contact with unsolubilized midcycle CM in vitro. SETTING: In vitro
      experiment. PATIENT(S): Healthy female volunteers from whom cervicovaginal lavage
      fluid and periovulatory CM were obtained. INTERVENTION(S): Changes in cytokine
      and Ig concentration in cervicovaginal lavage fluid after incubation with CM.
      MAIN OUTCOME MEASURE(S): Interleukin (IL)-4, IgA, and IgG concentrations were
      determined by ELISA. Interleukin-2 concentration was determined by bioassay using
      the IL-2-dependent cytotoxic T-lymphocyte cell line and ELISA. Results were
      expressed as percent antibody or cytokine recovery remaining after mucus contact,
      with differences over time evaluated by analysis of variance. RESULT(S): During
      18-hour mucus contact, significant changes were detected for IL-4, IgA, and IgG
      concentration. Interleukin-2 was stable in mucus-associated cervicovaginal lavage
      fluid as determined by functional bioassay and ELISA. CONCLUSION(S):
      Immunoglobulins and cytokines differ in their recovery from aqueous media after
      CM contact, suggesting that midcycle CM could alter immune reactivity within the
      reproductive tract by modifying the availability or function of immunomodulatory
      substances.

PMID- 8986683
TI  - In vitro culture of endometrial stromal and gland cells as a model for
      endometriosis: the effect of peritoneal fluid on proliferation.
AB  - OBJECTIVE: To test the hypothesis that the cell-free fraction of PF from women
      with endometriosis affects the proliferation of endometrial epithelial and
      stromal cells in vitro. DESIGN: A cell biologic and immunohistochemical study.
      SETTING: University teaching hospital. PATIENT(S): Premenopausal women undergoing
      laparoscopy and women with histologically normal endometrium undergoing
      hysterectomy were selected. INTERVENTION(S): Peritoneal fluid (PF) and serum were
      collected at laparoscopy. Endometrial epithelial and stromal cells were obtained
      by enzymic dissociation of tissue, and epithelium was separated from stromal
      cells by sieving. Epithelial and stromal cell populations were purified by
      removal of contaminating cells using Thy-1-and CD-45-labeled immunomagnetic
      beads. Isolated endometrial gland and stromal cells were cultured in the presence
      of PF or serum from women with and without endometriosis. MAIN OUTCOME
      MEASURE(S): Cell proliferation was assessed by measurement of incorporation of
      3[H]thymidine after 48 hours in culture. RESULT(S): Isolated endometrial gland
      and stromal cells were able to proliferate in vitro. The proliferative effect of
      PF or sera from women with endometriosis did not differ significantly from normal
      controls. CONCLUSION(S): We conclude that PF from women with endometriosis does
      not have an additional mitogenic effect compared with women without
      endometriosis. It may be postulated that the endometrium from women with
      endometriosis responds differently to the effects of PF.

PMID- 8986684
TI  - Cardioprotective effects of individual conjugated equine estrogens through their
      possible modulation of insulin resistance and oxidation of low-density
      lipoprotein.
AB  - OBJECTIVE: To examine the independent effects on insulin sensitivity and
      antioxidative activity of the three most prevalent constituents in Premarin
      (Wyeth-Ayerst Laboratories, Philadelphia, PA): estrone sulfate (E1S), 50%;
      equilin sulfate (EqS), 25%, and 17 alpha-dihydroequilin sulfate (17 alpha-ES),
      15%. DESIGN: Prospective randomized cross-over study. SETTING: University of
      Southern California Medical Center. PATIENT(S): Eight healthy postmenopausal
      women, mean age 53 +/- 2 years, and mean body mass index, 26 +/- 2 kg/m2, were
      enrolled. INTERVENTION(S): Each woman received, in randomized succession, daily
      oral doses of 17 alpha-ES (0.2 mg), E1S (0.625 mg), and EqS (0.3 mg) for 30 days.
      MAIN OUTCOME MEASURE(S): Oxidation of low-density lipoprotein (LDL) by negatively
      charged LDL (LDL-) and lag phase duration and measured the plasma glucose
      disappearance after insulin administration (K(itt)). RESULT(S): All three
      estrogen preparations demonstrated antioxidant effects with E1S demonstrating the
      most significant changes, followed by EqS and 17 alpha-ES. Using E1S, LDL-levels
      decreased from a baseline of 3.91 +/- 0.9 to 2.05 +/- 0.32 mg/dL and the lag time
      increased from 24.5 +/- 6.0 to 87.8 +/- 11.8 minutes. Changes in insulin
      tolerance tests revealed improved insulin action with the various estrogens. With
      EqS, K(itt) increased from 3.1% +/- 0.3% to 4.3% +/- 0.3% glucose/min, was
      intermediate with E1S and was least with 17 alpha-ES. CONCLUSION(S): All three
      conjugated equine estrogens demonstrated antioxidant activity. Also, some
      improved insulin action was demonstrated. To our knowledge, this is the first in
      vivo study to examine the effects of these components which may help explain, in
      part, some of the cardioprotective properties ascribed to Premarin.

PMID- 8986685
TI  - Acute effects of transdermal estradiol administration on plasma levels of nitric
      oxide in postmenopausal women.
AB  - OBJECTIVE: To investigate the acute effects of transdermal E2 administration on
      nitric oxide (NO) plasma levels in postmenopausal women. DESIGN: Randomized,
      placebo-controlled trial. SETTING: Normal human volunteers in an academic
      research environment. PATIENT(S): Twenty healthy postmenopausal women.
      INTERVENTION(S): Transdermal administration of 100 micrograms/d E2 or placebo.
      MAIN OUTCOME MEASURE(S): Plasma concentrations of NO stable oxidation products
      and serum concentrations of E2 were assessed before and 24 hours after the
      administration. RESULT(S): In the group treated with E2 mean concentration of NO
      metabolites 24 hours after patch application (37.31 +/- 7.62 mumol/L) resulted
      significantly higher than baseline (21.04 +/- 5.71 mumol/L) and the control group
      (23.50 +/- 4.03 mumol/L). The correlation between the mean percent increase in NO
      metabolites and absolute E2 concentrations 24 hours after the E2 administration
      was statistically significant. CONCLUSION(S): Transdermal administration of E2 to
      healthy postmenopausal women increases the plasma levels of NO and this supports
      the hypothesis that a NO-related mechanisms may contribute to the cardiovascular
      protective effect of estrogens in postmenopause.

PMID- 8986686
TI  - The effect of sequential three-monthly hormone replacement therapy on several
      cardiovascular risk estimators in postmenopausal women.
AB  - OBJECTIVE: To investigate the changes in plasma lipids and lipoproteins, low
      density lipoprotein (LDL) oxidizability, and plasma homocysteine during
      postmenopausal sequential 3-monthly hormone replacement therapy. DESIGN: Open
      longitudinal prospective study. SETTING: Gynecological outpatient department of a
      university hospital. PATIENT(S): Thirty-nine healthy nonhysterectomized
      postmenopausal women. INTERVENTION(S): Oral conjugated estrogen, 0.625 mg/d,
      combined with oral medrogestone 10 mg/d during the last 14 days of each 84-day
      treatment cycle. The treatment was given for four treatment cycles of 84 days (1
      year). MAIN OUTCOME MEASURE(S): Plasma lipids and lipoproteins, LDL
      oxidizability, and plasma homocysteine. RESULT(S): After 1 year of treatment
      plasma concentrations of total cholesterol and LDL cholesterol were 3.5% and 8.7%
      lower, respectively. High density lipoprotein cholesterol, apolipoprotein A-I,
      and triglycerides were 6.5%, 9.0% and 16% higher, respectively. Apolipoprotein B
      concentration remained unchanged. The results on LDL oxidizability were
      inconsistent. Plasma homocysteine decreased with 12.3% during the first 6 months
      of treatment in women with higher homocysteine concentrations at baseline. These
      values returned to baseline levels during the second half year of treatment.
      CONCLUSION(S): This sequential hormone regimen induced beneficial changes in the
      conventional lipid and lipoprotein risk estimators, whereas the observed changes
      in the other markers remained inconclusive and/or of minor importance.

PMID- 8986688
TI  - Frozen-thawed epididymal spermatozoa for intracytoplasmic sperm injection.
AB  - OBJECTIVE: To report the fertilization rate and pregnancy results for
      intracytoplasmic sperm injection (ICSI) cycles using frozen-thawed epididymal
      spermatozoa. DESIGN: Retrospective analysis of consecutive ICSI cycles. SETTING:
      Tertiary referral center for infertility. PATIENT(S): Infertile couples in whom
      39 patients (59 ICSI cycles) required the use of frozen-thawed epididymal
      spermatozoa. As no cycles were performed using fresh epididymal spermatozoa,
      outcomes were compared with those of 130 couples (170 ICSI cycles) using fresh
      ejaculated spermatozoa for severe oligoasthenozoospermia-teratozoospermia, in
      which < 200,000 motile spermatozoa were retrieved after Percoll density gradient
      centrifugation. INTERVENTION(S): Epididymal sperm aspiration during microsurgery,
      followed by ICSI. MAIN OUTCOME MEASURE(S): Fertilization, embryo cleavage, ET,
      and clinical pregnancy rates (PRs). RESULT(S): A total of 484 metaphase II
      oocytes were injected with frozen-thawed epididymal spermatozoa, resulting in a
      two-pronuclear fertilization rate per injected metaphase II oocyte of 47%,
      significantly lower than in cycles using fresh ejaculated spermatozoa (73%).
      Embryo implantation rates (12.0% versus 13.3%) and clinical PRs per transfer
      (18.4% versus 27.0%) were not different. When the prefreeze vitality was > 20%,
      compared with lower vitality, both the fertilization (56% versus 22%) and embryo
      cleavage (91% versus 57%) rates were significantly greater. CONCLUSION(S): The
      routine collection and cryopreservation of epididymal spermatozoa at microsurgery
      allows multiple ICSI treatment cycles with success rates similar to those of
      ejaculated spermatozoa. However, when the vitality of aspirated spermatozoa is <
      20%, the poor fertilization rates indicate the need to consider an alternative
      source of viable spermatozoa.

PMID- 8986689
TI  - The outcome of in vitro fertilization in unexplained habitual aborters concurrent
      with secondary infertility.
AB  - OBJECTIVE: To compare the IVF-ET reproductive performance of unexplained habitual
      aborters with nonaborting women with similar characteristics also treated with
      IVF-ET. DESIGN: Controlled clinical study. SETTING: In Vitro Fertilization Unit,
      Assaf Harofeh Medical Center, Zerifin, Israel. PATIENT(S): Twenty patients with
      habitual abortions and secondary infertility were subjected to 42 IVF-ET cycles.
      Their reproductive performance in IVF-ET was compared with the performance of the
      next followed nonaborting patients, pulled from a database, based on similar age
      and IVF indications. INTERVENTION(S): Ovulation induction with IM Depo
      triptorelin 3.75 mg and menotropins. Oocyte retrieval, embryo transfer, and
      luteal supplementation with hCG. MAIN OUTCOME MEASURE(S): Mean number of oocytes
      and fertilizations, mean number of embryos and their morphology. Pregnancy rates
      (PRs) and pregnancy outcome. RESULT(S): The mean number of oocytes,
      fertilizations, and embryos was higher in the aborters compared with the
      controls. Morphology of the transferred embryos was similar in both groups though
      in general better quality embryos developed in the aborters group. Pregnancy
      rates were similar in both groups (32% and 29% per cycle). Pregnancy outcome of
      the habitual aborting patients in IVF-ET remained unsuccessful, as before
      treatment: 50% abortions (7/14) compared with only an 8% abortion rate (1/12) in
      the controls. CONCLUSION(S): Habitual aborters' performance at early stages of
      IVF-ET is better compared with their controls. Despite similar PRs in IVF-ET
      cycles, their pregnancy outcome after IVF-ET is unsuccessful, as before IVF-ET.

PMID- 8986687
TI  - Quality of frozen-thawed testicular sperm and its preclinical use for
      intracytoplasmic sperm injection into in vitro-matured germinal-vesicle stage
      oocytes.
AB  - OBJECTIVE: To study the effects of cryopreservation on the quality of human
      testicular spermatozoa and the efficiency of intracytoplasmic sperm injection
      (ICSI) with frozen-thawed testicular sperm into metaphase II oocytes in vitro
      matured from the germinal-vesicle stage oocyte. DESIGN: Preclinical freezing
      study on supernumarary testicular spermatozoa after ICSI. SETTING: Tertiary IVF
      center coupled with an institutional research environment. PATIENT(S): Twenty
      nine patients undergoing excisional testicular biopsy for ICSI. INTERVENTION(S):
      Isolated testicular spermatozoa were cryopreserved and thawed; frozen-thawed
      motile testicular spermatozoa were microinjected. MAIN OUTCOME MEASURE(S):
      Prefreezing and post-thawing motility and viability, survival rate, fertilization
      rate, cleavage rate, and embryo quality after ICSI. RESULT(S): Mean percentage
      motility decreased from 21% before freezing to 6% after thawing. Vitality was
      impaired to a similar extent, decreasing from 68% to 22% (32% recovery rate).
      Injection of frozen-thawed testicular spermatozoa into in vitro-matured oocytes
      resulted in a fertilization rate of 50.9%. Cleavage rate was severely impaired.
      Half of the fertilized oocytes became arrested in the one-cell stage.
      CONCLUSION(S): Despite the low quality of the fresh testicular spermatozoa, a
      high percentage of prepared testicular sperm fractions showed survival and
      motility after the freezing and thawing process. Injection of frozen-thawed
      testicular sperm into matured oocytes resulted in fertilization rates comparable
      with these with fresh testicular sperm, but cleavage rates were severely
      impaired, which might be due to source of oocytes used for ICSI.

PMID- 8986690
TI  - Improved controlled ovarian hyperstimulation in poor responder in vitro
      fertilization patients with a microdose follicle-stimulating hormone flare,
      growth hormone protocol.
AB  - OBJECTIVE: To assess the efficacy of a novel protocol-microdose GnRH agonist
      (GnRH-a), FSH, and GH, for the stimulation of IVF patients who were canceled
      previously on a standard luteal GnRH-a, FSH, GH protocol. DESIGN: Prospective
      evaluation using the patient's previous IVF stimulation attempt as historic
      controls. SETTING: Private practice assisted reproductive technology center.
      PARTICIPANT(S): Thirty-two patients who had prior ovulation induction cycles
      canceled using luteal phase GnRH-a suppression followed by exogenous
      gonadotropins and GH. INTERVENTION(S): Precycle treatment with oral
      contraceptives followed by follicular phase administration of 40 micrograms
      leuprolide acetate every 12 hours beginning on cycle day 3 and FSH supplemented
      with GH beginning on cycle day 5. MAIN OUTCOME MEASURE(S): Paired analysis of E2
      day 5, number of follicles, ampules of FSH required, and cancellation rate. The
      number of oocytes, embryos, embryo quality, implantation rate, and pregnancy rate
      (PR) were determined for completed cycles on the microdose GnRH-a, FSH, GH
      protocol. RESULT(S): Controlled ovarian hyperstimulation was superior during
      microdose GnRH-a, FSH, GH stimulation when compared with the prior luteal GnRH-a
      cycle. Specifically, there was a higher E2 response, more oocytes, fewer cycle
      cancellations, and no premature LH surge or luteinization. The microdose GnRH-a,
      FSH, GH protocol produced an average of 10 oocytes and a 50% ongoing PR.
      CONCLUSION(S): The microdose GnRH-a, FSH, GH protocol is superior to standard
      protocols for the treatment of patients with decreased ovarian reserve undergoing
      controlled ovarian hyperstimulation for IVF.

PMID- 8986691
TI  - Processing of semen in an antibiotic-rich culture medium to minimize microbial
      presence during in vitro fertilization.
AB  - OBJECTIVE: To identify and determine the prevalence of microorganisms in
      preprocessed and postprocessed semen in an IVF-ET program. DESIGN: Prospective
      study. SETTING: University Teaching Hospital. PATIENT(S): Seventy-four men
      undergoing preprogram evaluation, each producing two semen samples.
      INTERVENTION(S): Semen processing with a wash and swim-up technique in a
      penicillin- and streptomycin-rich medium. MAIN OUTCOME MEASURE(S): The identity
      and prevalence of seminal microorganisms before and after processing. RESULT(S):
      Sixty-three percent of individual unprocessed semen samples grew microorganisms,
      the majority of which were nonpathogenic. Thirty-three men (44.6%) had microbes
      identified in repeat samples, four had identical organisms each time. Twenty
      (27%) had positive cultures in one sample, negative in the other. Twenty-one
      (28.4%) had consistently sterile semen. After seminal processing, the recovery
      rate for microbes was 5%. Microbial presence after processing did not correlate
      with either the sperm swim-up concentration or the initial microbial
      concentration. CONCLUSION(S): Bacteriospermia is common. The microorganisms found
      rarely are replicated and most likely represent contamination. Wash and swim-up
      semen preparation in an antibiotic rich culture medium effectively eliminates 95%
      of organisms.

PMID- 8986692
TI  - Hemostasis parameters during ovarian stimulation for in vitro fertilization:
      results of a prospective study.
AB  - OBJECTIVE: To evaluate the effect of IVF-ET on the hemostatic system. DESIGN:
      Prospective clinical study. SETTING: Apparently healthy age-matched women of the
      hospital staff at various stage of the menstrual cycle. PATIENT(S): Twenty-five
      women involved in a IVF-ET program at the Department of Obstetrics and
      Gynecology, Montpellier University Hospital. INTERVENTION(S): Twenty-six
      hemostasis parameters evaluated repeatedly in patients undergoing IVF-ET. MAIN
      OUTCOME MEASURE(S): Blood cell-dependent hemostasis parameters and plasmatic
      coagulation factors, determined at pituitary desensitization, maximal E2 level,
      and P plateau. RESULT(S): Activation of the hemostatic system is evidenced at the
      P plateau, when D-dimers and fragments 1 + 2 of the prothrombin levels rose
      dramatically. At E2 peak, no significant modification of hemostasis markers was
      noted. CONCLUSION(S): The present results indicate that ovarian hyperstimulation
      may induce hemostasis activation at the P plateau. The role of supraphysiologic
      sex hormone levels on the hemostatic system requires further investigation.

PMID- 8986693
TI  - Day 3 serum inhibin-B is predictive of assisted reproductive technologies
      outcome.
AB  - OBJECTIVE: To determine if women with day 3 serum inhibin-B concentrations < 45
      pg/mL (conversion factor to SI unit, 1.00) demonstrate a poorer response to
      ovulation induction and assisted reproductive technologies outcome relative to
      women with inhibin-B values > or = 45 pg/mL. DESIGN: Analysis of inhibin-B, FSH,
      and E2 concentrations in day 3 serum samples. SETTING: Academic clinical
      practice. PATIENT(S): One hundred fifty-six women who underwent 178 assisted
      reproductive technology (ART) cycles with luteal phase GnRH agonist suppression
      plus hMG and urofollitropin stimulation. MAIN OUTCOME MEASURE(S): Serum E2 on day
      of hCG, number of oocytes retrieved per patient, fertilization rate, cleavage
      rate, clinical pregnancy rate (PR) per initiated cycle, cancellation rate per
      initiated cycle, and spontaneous abortion rate. RESULT(S): Women with day 3 serum
      inhibin-B < 45 pg/mL demonstrated 70% of the E2 response, had 66.6% of the number
      of oocytes retrieved per patient, with 28% of the clinical PR per initiated
      cycle, and three times the cancellation rate per initiated cycle than women with
      day 3 inhibin-B > or = 45 pg/mL. After controlling for age, day 3 serum FSH, day
      3 serum E2, patient cycle number, and method of ART, day 3 serum inhibin-B > or =
      45 pg/mL was noted to be prognostic of the number of oocytes retrieved and
      clinical PR. The adjusted odds ratio of clinical pregnancy for those with day 3
      serum inhibin-B > or = 45 pg/mL versus those with inhibin-B < 45 pg/mL was 6.8
      (95% confidence interval 1.8 to 25.6). CONCLUSION(S): Women with low day 3 serum
      inhibin-B concentrations demonstrate a poorer response to ovulation induction and
      are less likely to conceive a clinical pregnancy through ART relative to women
      with high day 3 inhibin-B.

PMID- 8986694
TI  - Premature plasma progesterone and androgen elevation are not prevented by adrenal
      suppression in in vitro fertilization.
AB  - OBJECTIVE: To investigate the effects of adrenal suppression with dexamethasone
      (DEX) on P and androgen profiles during controlled ovarian hyperstimulation (COH)
      for IVF-ET. DESIGN: Prospective controlled trial. SETTING: In vitro fertilization
      program, Clamart, France. PATIENT(S): One hundred twenty IVF-ET candidates aged
      25 to 39 years undergoing 120 COH cycles. INTERVENTION(S): Group A: 60 women
      received a time-release GnRH agonist (GnRH-a) on cycle day 2. After pituitary
      desensitization was confirmed, 1 mg/d DEX was administered daily until hCG.
      Ovarian stimulation with hMG was started on the 7th day of DEX. Group B: 60 other
      women received an identical treatment except DEX was omitted. MAIN OUTCOME
      MEASURE(S): Plasma E2, P, androstenedione (A), and T were measured 18 days after
      GnRH-a, on the 7th day of DEX in group A, and on the day of hCG. RESULT(S): Peak
      plasma E2 levels were similar in groups A and B. After GnRH-a, P and androgen
      levels were low in both groups. In group A, an additional decrease in these
      hormones was observed after 7 days of DEX. During COH, we observed similar
      absolute increases of P, A, and T in groups A (+0.52, +1.56, and +0.12 ng/mL,
      respectively) and B (+0.55, +1.66, and +0.17 ng/mL, respectively). CONCLUSION(S):
      As expected, DEX lowered additionally P, A, and T levels from values achieved
      after GnRH-a alone, reflecting the adrenal contribution to the circulating levels
      of these hormones at baseline. Yet, the net increases in P, A, and T seen in COH
      were unaltered by DEX treatment, indicating that this phenomenon results solely
      from an effect of exogenous gonadotropins on the ovary.

PMID- 8986695
TI  - A simplified coculture system with luteinized granulosa cells improves embryo
      quality and implantation rates: a controlled study.
AB  - OBJECTIVE: To investigate the use of a simplified short-term coculture system
      with luteinized granulosa cells (GCs) in patients with failed IVF-ET. DESIGN:
      Controlled clinical study. SETTING: IVF unit, Department of Obstetrics and
      Gynecology, Carmel Medical Center. PATIENT(S): Patients with poor embryo quality
      in their previous IVF-ET cycles. INTERVENTION(S): Embryos from 40 patients, in
      which > 50% of the embryos were classified as poor quality in their previous IVF
      attempts, were grown on autologue GC culture system for a short period (24-48
      hours) before being replaced in the uterine cavity. MAIN OUTCOME MEASURE(S):
      Embryo quality. RESULT(S): Significant decrease in poor quality embryos and
      increase in the proportion of good quality embryos were observed using a
      coculture system with autologue human GCs. Pregnancy rates in this groups of
      patients reached our standard IVF results during the same period. CONCLUSION(S):
      This study describes a simplified short-term coculture system with human
      autologue GCs. Poor quality embryos may be rescued to cleave regularly.

PMID- 8986696
TI  - Changes in protamine 1 distribution in human sperm nucleus during in vitro sperm
      oocyte interaction: an immunoelectron microscopic study.
AB  - OBJECTIVE: To determine whether the process of sperm nuclear destabilization
      would begin before sperm-oocyte fusion in humans. DESIGN: Changes in the
      distribution of human protamine 1 were investigated in human spermatozoa from the
      ejaculate, in spermatozoa selected by swim-up or Percoll techniques, and in
      spermatozoa bound to zona pellucida (ZP) from oocytes that failed to fertilize in
      an IVF program. SETTING: Center for Infertility and Assisted Reproductive
      Technology, and university departments. PATIENT(S): Fifteen couples undergoing an
      IVF program. INTERVENTION(S): Women underwent a similar superovulation induction
      protocol that consisted of GnRH agonist associated with hMG. MAIN OUTCOME
      MEASURE(S): Comparative immunoelectron microscopic study of sperm nucleus
      labeling with an anti-human protamine 1 specific protamine monoclonal antibody.
      RESULT(S): After selection by swim-up or by Percoll, spermatozoa show a
      significantly lower nuclear labeling than in the ejaculate. After binding to the
      ZP, labeling increases, more in spermatozoa selected by swim-up than by Percoll,
      but, after Percoll selection, labeling in zona-bound spermatozoa is lower than in
      the ejaculate. CONCLUSION(S): In humans sperm binding to the ZP induces
      differences in the accessibility of the anti-human protamine 1 antibody, which
      are consistent with structural rearrangements of the DNA-nucleoproteins complex.
      These modifications must be a prelude to sperm decondensation, protamines
      replacement by histones, and subsequent reactivation of the sperm genome in the
      oocyte.

PMID- 8986697
TI  - Correlation between semen parameters of electroejaculates and achieving pregnancy
      by intrauterine insemination.
AB  - OBJECTIVE: To investigate whether any parameter in the routine semen analysis of
      electroejaculates is correlated with success in achieving pregnancy by IUI.
      DESIGN: Retrospective observational study. SETTING: An Assisted Reproductive
      Program at a tertiary care university center. PATIENT(S): Twenty-seven
      anejaculatory men with spinal cord injury (n = 24) or history of retroperitoneal
      lymph node dissection (n = 3), thirteen of whom attempted conception with their
      wives. INTERVENTION(S): Anejaculatory men underwent rectal probe
      electroejaculation and electroejaculates were used for IUI. MAIN OUTCOME
      MEASURE(S): Statistical correlation of semen parameters between electroejaculates
      that resulted in pregnancy and those that did not. RESULT(S): Seven pregnancies
      resulted from 56 IUIs using electroejaculates (pregnancy rate = 12.5% per IUI).
      The total motile sperm count and percentage of normal morphology were
      significantly higher in the specimens that resulted in pregnancies than those
      that did not. However, there was no statistically significant difference observed
      in pH, sperm concentration, or percentage of motility between the two groups.
      Swim-up techniques used to process electroejaculates significantly improved the
      motility of the specimens. No pregnancy occurred beyond the fifth IUI attempt.
      Repeated electroejaculation and duration of spinal cord injury had no effect on
      the quality of the ejaculates. CONCLUSION(S): The total motile sperm count and
      the percentage normal morphology of electroejaculates correlate with success in
      achieving pregnancy by IUI. Because repeated electroejaculation does not improve
      quality of ejaculate, the initial semen analysis of electroejaculates is not only
      useful in counseling couples undergoing such treatment program but should be
      planned for use as an inseminate.

PMID- 8986698
TI  - Fertility options after vasectomy: a cost-effectiveness analysis.
AB  - OBJECTIVE: To evaluate cost per delivery using two different initial approaches
      to the treatment of postvasectomy infertility. DESIGN: Model of expected costs
      and results in the United States in 1994. SETTING: Men with postvasectomy
      infertility, evaluated and treated at centers with experience in vasectomy
      reversal or sperm retrieval and ICSI. PATIENT(S): Men with postvasectomy
      infertility, with a female partner < or = 39 years of age. INTERVENTION(S):
      Initial microsurgical vasectomy reversal was compared with retrieved epididymal
      or testicular sperm. Actual treatment charges, complication rates, and pregnancy
      and delivery rates obtained in the United States were used for cost per delivery
      analysis. MAIN OUTCOME MEASURE(S): Cost per delivery, delivery rates. RESULT(S):
      Cost per delivery with an initial approach of vasectomy reversal was only
      $25,475. (95% confidence interval $19,609 to $31,339), with a delivery rate of
      47%. However, the cost per delivery after sperm retrieval and ICSI was $72,521.
      (95% confidence interval $63,357 to $81,685), with an average of $73,146 for
      percutaneous or testicular sperm retrieval and $71,896 for surgical epididymal
      sperm retrieval. The delivery rate after one cycle of sperm retrieval and ICSI
      was 33%. CONCLUSION(S): The most cost-effective approach to treatment of
      postvasectomy infertility is microsurgical vasectomy reversal. This treatment
      also has the highest chance of resulting in delivery of a child for a single
      intervention.

PMID- 8986699
TI  - Comparison of individual antioxidants of sperm and seminal plasma in fertile and
      infertile men.
AB  - OBJECTIVE: To measure individual antioxidants in sperm and seminal plasma from
      fertile and infertile men to determine if any particular antioxidant is reduced
      in infertile men. DESIGN: Semen samples were prepared by a discontinuous Percoll
      gradient to separate sperm and seminal plasma, and the antioxidant concentrations
      of each were assessed. Samples also were screened for phorbol ester-induced
      reactive oxygen species (ROS) activity. SETTING: Departments of Obstetrics and
      Gynaecology, and Clinical Biochemistry, The Queen's University of Belfast,
      Northern Ireland. PATIENT(S): Fifty-nine male patients attending our infertility
      center: 18 men whose wives had ongoing pregnancies from IVF with normozoospermic
      semen profiles, 20 infertile men with normozoospermic and 21 men with
      asthenozoospermic semen profiles. MAIN OUTCOME MEASURE(S): Ascorbate, urate,
      sulphydryl groups, tocopherol and carotenoid concentrations were measured in
      sperm and seminal plasma from fertile and infertile men. RESULT(S): In seminal
      plasma, ascorbate contributes almost twice as much as urate and thiol levels are
      about one third of ascorbate. Ascorbate levels in seminal plasma of
      asthenozoospermic individuals (+ROS) are significantly reduced. In sperm, thiols
      contributed most and ascorbate only a fraction of the total. CONCLUSION(S): In
      seminal plasma, ascorbate, urates, and thiols are the major antioxidants present.
      In contrast, within sperm, this group is the major contributor. In samples
      exhibiting ROS activity, ascorbate concentrations in the seminal plasma are
      significantly reduced.

PMID- 8986700
TI  - Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female
      macaques.
AB  - OBJECTIVE: To examine the effects of soy phytoestrogens on coronary vascular
      reactivity in atherosclerotic male and female rhesus monkeys. DESIGN: A
      prospective, randomized, blinded, controlled study. SETTING: Comparative Medicine
      Clinical Research Center of an academic medical center. PATIENT(S): Twenty-two
      young adult rhesus monkeys with pre-existing diet-induced atherosclerosis.
      INTERVENTION(S): Monkeys were fed soy-based diets for 6 months identical in
      composition, except that the isoflavones were extracted from one flow-isoflavone)
      and intact in the other (high-isoflavone). Quantitative coronary angiography was
      performed at the end of the study period. Females in the low-isoflavone group
      under went a second angiography after an acute IV dose of genistein. MAIN OUTCOME
      MEASURE(S): Percent change in diameter of the proximal left circumflex coronary
      artery in response to intracoronary acetylcholine and nitroglycerin, compared
      with control diameter. RESULT(S): Arteries from males constricted in response to
      acetylcholine. Arteries from females in the low-isoflavone group constricted (
      6.2% +/- 2.8%, mean +/- SEM), whereas arteries from females in the high
      isoflavone group dilated (6.4% +/- 1.2%, mean +/- SEM). Intravenous
      administration of genistein caused dilation in the previously constricting low
      isoflavone females (3.3% +/- 2.8%). CONCLUSION(S): Like mammalian estrogens,
      dietary soy isoflavones enhance the dilator response to acetylcholine of
      atherosclerotic arteries in female monkeys.

PMID- 8986702
TI  - Prenatal diagnosis of ring chromosome 14 after intracytoplasmic sperm injection.
AB  - OBJECTIVE: To collect extensively abnormal cytogenetic results in pregnancies
      obtained after intracytoplasmic sperm injection (ICSI). DESIGN: Case report.
      SETTING: University Hospital of Nantes, France. PATIENT(S): A couple with 5 years
      of primary infertility and severe male factor undergoing ICSI procedure.
      INTERVENTION(S): Ultrasound-guided transvaginal follicular aspiration,
      amniocentesis, and medical abortion. MAIN OUTCOME MEASURE(S): Serum levels of E2,
      beta-hCG, and fetal chromosomal karyotype. RESULT(S): Ultrasonic observation at
      12 weeks revealed an 8-mm thick cystic hygroma in the nuchal area. Because the
      karyotypic analysis was [46,XX,r(14)/45,XX,-14], medical abortion was performed
      at 14 weeks, after the patients gave their informed consent. CONCLUSION(S):
      According to the prevalence of this unusual chromosomal abnormality in humans,
      such abnormal cytogenetic results have to be collected extensively to assess the
      feasibility of using ICSI procedure.

PMID- 8986701
TI  - Prenatal exposure of female rhesus monkeys to testosterone propionate increases
      serum luteinizing hormone levels in adulthood.
AB  - OBJECTIVE: To determine whether prenatal androgenization of the developing
      primate hypothalamohypophyseal unit induces irreversible changes in LH secretion.
      DESIGN: Prospective nonrandomized study. SETTING: An academic research
      environment. ANIMALS: Forty-one adult ovulatory female rhesus monkeys.
      INTERVENTION(S): Seventeen female rhesus monkeys exposed prenatally to
      testosterone propionate (female pseudohermaphrodites) and 24 normal females
      underwent blood sampling over two ovulatory menstrual cycles. MAIN OUTCOME
      MEASURE(S): Serum FSH, LH, E2, and T were determined by RIA; P was determined by
      enzyme immunoassay. Serum bioactive LH was measured by mouse Leydig cell
      bioassay. RESULT(S): Tonic immunoactive LH hypersecretion and normal FSH release
      occurred in female pseudohermaphrodites compared with normal females.
      Periovulatory immunoactive LH and FSH secretion was similar in both female types,
      whereas a relative increase in the amount of circulating bioactive LH to
      immunoactive LH was found at midcycle in female pseudohermaphrodites versus
      normal females. The length of the follicular phase was unaffected by prenatal
      androgen exposure, but the slopes of serum T and E2 concentrations versus
      follicular phase cycle day were significantly lower in female
      pseudohermaphrodites than normal females. Luteal phase length and P secretion
      were comparable in both types of females. CONCLUSION(S): Androgen exposure during
      primate neural differentiation may alter permanently the pattern of LH secretion
      in the presence of cyclic gonadotropin release.

PMID- 8986703
TI  - Comparison of synthetic serum substitute and fetal cord serum as media
      supplements for in vitro fertilization: a prospective, randomized study.
AB  - OBJECTIVE: To compare the value of synthetic serum substitute and fetal cord
      serum (FCS) as protein supplements in the media used for IVF. DESIGN:
      Prospective, randomized study of 45 patients undergoing IVF. SETTING: Private
      infertility practice. INTERVENTION(S): The protein supplement for use in IVF
      medium was randomized prospectively to synthetic serum substitute or FCS. MAIN
      OUTCOME MEASURE(S): Oocyte fertilization rate, incidence of embryo arrest, number
      of embryos transferred, ongoing pregnancy rate, and implantation rate were
      assessed. RESULT(S): There was no significant difference in the fertilization
      rate, incidence of embryo arrest, number of embryos transferred, ongoing
      pregnancy rate, and implantation rate. CONCLUSION(S): Synthetic serum substitute
      is a better alternative to FCS as a protein supplement for IVF because of its
      availability and cost effectiveness. Synthetic serum substitute can be used in
      culture medium for sperm washing, insemination, culture, and transfer translating
      to decreased technician time without a significant difference in fertilization,
      pregnancy, or implantation rate.

PMID- 8986704
TI  - Massive ovarian enlargement in primary hypothyroidism.
AB  - OBJECTIVE: To report a case of ovarian cyst formation and myxedematous
      infiltration of the ovary in a subject with primary hypothyroidism. DESIGN:
      Retrospective case report. SETTING: University hospital. PATIENT(S): A 16-year
      old female adolescent with pelvic pain, galactorrhea, irregular menses, and
      ovarian cysts on pelvic examination. INTERVENTION(S): Laparotomy with bilateral
      ovarian wedge resection and thyroid replacement therapy. MAIN OUTCOME MEASURE(S):
      Ovarian histopathology, thyroid function tests, and menstrual history. RESULT(S):
      Resolution of patient's pain, galactorrhea, and resumption of normal menses.
      CONCLUSION(S): Ovarian cyst formation may accompany primary hypothyroidism in the
      child with accelerated or delayed sexual maturation. To date, the underlying
      pathophysiology of the morphological changes in the ovary remain enigmatic. This
      case report provides the first insight into the actual histologic changes that
      occur in ovaries of subjects with primary hypothyroidism without secondary
      ovarian pathology such as torsion. There is clear evidence of myxedematous
      infiltration into the ovarian stroma without luteinization of the theca interna.
      These microscopic findings suggest that local changes occurring independent of
      gonadotropin stimulation may contribute significantly to altered morphology of
      the ovaries in primary hypothyroidism.

PMID- 8986706
TI  - Future letters--"workshops on Internet".

PMID- 8986705
TI  - Surgical management of complete obliteration of the endometrial cavity.
AB  - OBJECTIVE: To describe a technique for surgical management of complete
      obliteration of the endometrial cavity. DESIGN: A report of a series of three
      patients. SETTING: A university-based hospital. PATIENT(S): Three patients with
      complete obliteration of the endometrial cavity. INTERVENTION(S): Transfundal
      scar removal using stents in the fallopian tubes to serve as landmarks. MAIN
      OUTCOME MEASURE(S): Regular withdrawal bleeding. RESULT(S): Regular menses in all
      three patients. CONCLUSION(S): The technique described here show promise for
      establishing uterine cavity integrity in cases of complete endometrial
      obliteration where there are no landmarks in the uterine cavity.

PMID- 8986707
TI  - Future letters--"workshops on Internet".

PMID- 8986708
TI  - Future letters--"workshops on Internet".

PMID- 8986709
TI  - A very sticky riddle.

PMID- 8986710
TI  - A very sticky riddle.

PMID- 8986711
TI  - Receptor editing, immune diversification, and self-tolerance.

PMID- 8986712
TI  - Characterization of the first definitive hematopoietic stem cells in the AGM and
      liver of the mouse embryo.
AB  - At day 10 in mouse gestation, the intraembryonic aorta-gonads-mesonephros (AGM)
      region generates the first definitive hematopoietic stem cells (HSCs) of the
      adult blood system. By 11 days postcoitum, the liver contains such HSCs. While
      HSCs of the adult bone marrow and late-stage fetal liver have been extensively
      characterized for cell surface markers, there has been no phenotypic description
      of the first HSCs during embryo development. We report here the temporal cell
      surface phenotype of HSCs from the AGM region and early fetal liver and show that
      all HSCs reside in the c-kit+ population. c-kit+ HSCs from AGM and liver are
      mainly CD34+ and in the AGM are in both Mac-1+ and Mac-1 fractions. These results
      demonstrate that during mouse ontogeny the first definitive HSCs are similar in
      cell surface phenotype to the HSCs of adult bone marrow but that spatial
      localization and developmental time are critical factors in the phenotypic
      assessment of this functional cell population.

PMID- 8986713
TI  - Identification of the earliest B lineage stage in mouse bone marrow.
AB  - We have identified a very early stage of B lineage cells in the CD45R (B220)+CD24
      (HSA) pre-pro-B fraction of mouse bone marrow delineated by expression of AA4.1,
      a molecule found on stem cells and early B lineage cells. These cells are B
      lineage precursors based on their capacity to generate B lineage cells rapidly in
      stromal-dependent culture and their expression of high levels of germline IgH
      transcripts in the absence of Rag-1/2. Half of these AA4.1+ precursors express
      low levels of CD4, characteristic of lymphoid progenitors, but few if any have up
      regulated CD19, a molecule expressed very early in the B lineage. Furthermore,
      expression of genes encoding pre-B and B cell receptor components (mb-1, B29, and
      lambda 5) and transcription factors necessary for B lineage differentiation
      (BSAP, E12, E47, and Id) provide further support for designating these cells as
      the earliest B cell precursors.

PMID- 8986714
TI  - Selective defects in the development of the fetal and adult lymphoid system in
      mice with an Ikaros null mutation.
AB  - Mice homozygous for an Ikaros null mutation display distinct defects in the
      development of fetal and adult lymphocytes. Fetal T lymphocytes, and fetal and
      adult B lymphocytes and their earliest progenitors are absent. Postnatally,
      hematopoietic stem cells give rise to thymocyte precursors that undergo aberrant
      differentiation into the CD4 lineage and clonal expansion. The lack of NK cells
      and some gamma delta T cell subsets and a large reduction in thymic dendritic
      APCs suggest that Ikaros is essential for establishing early branch points in the
      postnatal T cell pathway. The lymphoid defects detected in Ikaros null mice
      reveal critical molecular differences between fetal and postnatal hematopoietic
      progenitors that dictate their ability to give rise to T cells. These studies
      also establish Ikaros as a tumor suppressor gene acting during thymocyte
      differentiation. Phenotypic comparison of this null mutation with a severe
      dominant-negative Ikaros mutation identifies molecular redundancy in the
      postnatal hemolymphoid system.

PMID- 8986715
TI  - CD22 is both a positive and negative regulator of B lymphocyte antigen receptor
      signal transduction: altered signaling in CD22-deficient mice.
AB  - B cell activation following antigen receptor cross-linking can be augmented in
      vitro by ligation of cell surface CD22, which associates with the SHP1 protein
      tyrosine phosphatase. The targeted deletion of CD22 in mice demonstrated that
      CD22 differentially regulates antigen receptor signaling in resting and antigen
      stimulated B lymphocytes. B cells from CD22-deficient mice exhibited the cell
      surface phenotype and augmented intracellular calcium responses characteristic of
      chronically stimulated B cells, as occurs in SHP1-defective mice. Thus, CD22
      negatively regulates antigen receptor signaling in the absence of antigen.
      However, activation of CD22-deficient B lymphocytes by prolonged IgM cross
      linking resulted in modest B cell proliferation, demonstrating that CD22
      positively regulates antigen receptor signaling in the presence of antigen.

PMID- 8986716
TI  - Corepression of RelA and c-rel inhibits immunoglobulin kappa gene transcription
      and rearrangement in precursor B lymphocytes.
AB  - Multiple members of the NF-kappa B/Rel protein family are induced during B cell
      differentiation and have been implicated in transcriptional activation of the
      immunoglobulin kappa (Ig kappa) locus. Despite these findings, normal numbers of
      Ig kappa + B lymphocytes are produced by mice bearing targeted mutations in
      individual NF-kappa B/Rel genes. In the present study, precursor B lymphocytes
      were engineered to express a trans-dominant form of I kappa B alpha that
      simultaneously impairs the c-Rel and RelA transactivating subunits of NF-kappa B.
      This dual block in NF-kappa B/Rel signaling led to potent inhibition of germline
      Ig kappa transcription and rearrangement, whereas recombinase activity was
      unaffected. These findings suggest that c-Rel and RelA serve compensatory
      functional roles in the developmental mechanisms that govern Ig kappa gene
      assembly.

PMID- 8986717
TI  - A conserved degradation signal regulates RAG-2 accumulation during cell division
      and links V(D)J recombination to the cell cycle.
AB  - The proteins RAG-1 and RAG-2 are essential for initiation of V(D)J recombination.
      In dividing cells, RAG-2 accumulates during G1 and is undetectable during the S
      and G2/M cell cycle phases. A conserved degradation signal, including an
      essential CDK phosphorylation site at Thr-490, regulates RAG-2 accumulation
      during cell division and links V(D)J recombination to the cell cycle. Mutations
      within this signal abolish periodic degradation of RAG-2 protein in dividing
      cells. In mice expressing endogenous or wild-type transgenic RAG-2, V(D)J
      recombination intermediates accumulate preferentially in G0/G1 thymocytes; this
      restriction is relieved by mutation of Thr-490 to alanine (T490A). Thus, periodic
      destruction of RAG-2 protein couples V(D)J recombination to cell cycle phase.
      Using transgenic mice expressing the T490A RAG-2 mutant and a functional T cell
      receptor beta chain, we demonstrate that coupling of V(D)J recombination to the
      cell cycle is not essential for enforcement of allelic exclusion.

PMID- 8986718
TI  - Functional and physical interactions of Syk family kinases with the Vav proto
      oncogene product.
AB  - Syk family kinases are essential for lymphocyte development and activation.
      Therefore the identification of their direct effectors is of critical importance.
      Here, we report that Syk interacts in the yeast two-hybrid system with Vav, a
      proto-oncogene product exclusively expressed in hematopoietic cells. This
      interaction was direct, required the catalytic activity of Syk, the SH2 domain of
      Vav, and tyrosine residues in the linker domain of Syk. Vav also associated with
      Syk and Zap in antigen receptor-stimulated B or T cells, respectively.
      Functionally, Vav was phosphorylated by Syk family kinases both in vivo and in
      vitro. Furthermore, Syk and Vav cooperated to activate NF-AT synergistically.
      These results indicate that the interaction between Syk family kinases and Vav
      plays an important role in coupling immune recognition receptors to signaling
      pathways involved in lymphokine production.

PMID- 8986719
TI  - Signaling via IL-2 and IL-4 in JAK3-deficient severe combined immunodeficiency
      lymphocytes: JAK3-dependent and independent pathways.
AB  - Both IL-2 and IL-4 bind to receptors containing the common gamma chain and JAK3.
      Although JAK3 is required for proper lymphoid development, the precise roles of
      this kinase in IL-2 and IL-4 signaling in lymphocytes have not been defined.
      Here, we have studied IL-2 and IL-4 signaling in B cell lines lacking JAK3.
      Although IL-2-induced phosphorylation of IL-2R beta, JAK1, and STAT5 all required
      the presence of JAK3, IL-4-mediated phosphorylation of JAK1, STAT6, and insulin
      receptor substrates 1 and 2 did not. However, IL-4-induced effects were clearly
      improved following JAK3 expression. These data indicate that IL-4 signaling
      occurs in the absence of of JAK3, but is comparatively inefficient. These
      findings may help in understanding the pathogenesis of the immunodeficiency that
      occurs with mutations of JAK3 and may suggest a mechanism for the pleiotropic
      effects of IL-4.

PMID- 8986720
TI  - Fas modulation of apoptosis during negative selection of thymocytes.
AB  - A major mechanism maintaining immune tolerance is the deletion of potentially
      autoreactive thymocytes by apoptosis during development in the thymus. Previous
      reports suggest that apoptosis is induced by high avidity signals transduced via
      the T cell receptor; however, the role of signals transduced by other cell
      surface receptors during thymic selection remains poorly understood. Fas, a
      member of the TNF receptor family, has been shown to induce apoptosis in mature
      peripheral T cells; however, the effects of Fas on negative selection of
      thymocytes have not been previously detected. Using a sensitive terminal
      deoxynucleotidyl transferase method to detect apoptotic cells, we found that
      mutant Fas molecules in lpr mice decrease the sensitivity of thymocytes to T cell
      receptor-mediated apoptosis and that blockade of Fas-Fas ligand interactions in
      vivo can inhibit antigen-induced apoptosis of thymocytes in non-lpr mice. Thus,
      we have shown that Fas, in conjunction with antigen-specific signals, can
      modulate apoptosis during negative selection of thymocytes.

PMID- 8986721
TI  - Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK
      cells inhibits FcR-initiated tyrosine kinase activation.
AB  - Recognition of major histocompatibility (MHC) class I complexes on target cells
      by killer cell inhibitory receptors (KIR) blocks natural killer (NK) and T cell
      cytotoxic function. The inhibitory effect of KIR ligation requires the
      phosphotyrosine-dependent association of KIR with the cytoplasmic SH2-containing
      protein tyrosine phosphatase SHP-1. Using a somatic genetic model, we first
      define a requirement for the Src family protein tyrosine kinase (PTK) Lck in
      mediating KIR tyrosine phosphorylation. We then investigate how KIR ligation
      interrupts PTK-dependent NK cell activation signals. Specifically, we show that
      KIR ligation inhibits the Fc receptor (FcR)-induced tyrosine phosphorylation of
      the FcR-associated zeta signaling chain, the PTK ZAP-70, and phospholipase C
      gamma. Overexpression of catalytically inactive SHP-1 (acting as a dominant
      negative) restores the tyrosine phosphorylation of these signaling events and
      reverses KIR-mediated inhibition of NK cell cytotoxic function. These results
      suggest sequential roles for Lck and SHP-1 in the inhibition of PTK following MHC
      recognition by NK cells.

PMID- 8986722
TI  - The role of somatic mutation in the generation of the protective humoral immune
      response against vesicular stomatitis virus.
AB  - During most clinically relevant infections with cytopathic viruses, neutralizing
      antibodies are generated early, i.e., within the first week of infection. As
      early as 4 days after immunization of mice with vesicular stomatitis virus (VSV),
      a cytopathic virus closely related to rabies virus, hybridomas could be isolated
      that secreted virus-neutralizing IgGs. Such antibodies were devoid of somatic
      mutations, showed high binding avidities (approximately 10(9) M-1), and used V
      gene fragments predominantly belonging to the VHQ52 and VK19-28 families. In
      contrast, most secondary and hyperimmune response IgGs isolated 12 and 150 days
      after infection used several additional V gene combinations. These, which used
      the VHQ52/VK19-28 combination of early IgGs, were point mutated but showed only
      marginally enhanced binding avidities. Since all VHQ52/ VK19-28-positive IgGs
      bound to one subsite within the major antigenic site of VSV-G irrespective of the
      presence or absence of somatic point mutations, fine specificity diversification
      of secondary and hyperimmune responses was achieved by newly appearing V gene
      combinations.

PMID- 8986723
TI  - A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a
      homeostatic mechanism in inflammation.
AB  - In mice selectively deficient in CD11b/CD18, a beta 2 integrin, chemoattractant
      induced leukocyte adhesion to microvascular endothelium in vivo was reduced.
      Paradoxically, thioglycollate-induced neutrophil accumulation in the peritoneal
      cavity was increased and was associated with a significant delay in apoptosis of
      extravasated cells. The extravasated cells had a near absence of neutrophil
      phagocytosis and a reduction in oxygen free radical generation, which may
      contribute to the observed defect in apoptosis. This is supported by our in vitro
      studies, in which phagocytosis of opsonized particles by human neutrophils
      rapidly induced apoptosis that could be blocked with CD11b/ CD18 antibodies.
      Reactive oxygen species are the intracellular link in this process: phagocytosis
      induced apoptosis was blocked both in neutrophils treated with the flavoprotein
      inhibitor diphenylene iodonium and in neutrophils from patients with chronic
      granulomatous disease, which lack NADPH oxidase. Thus, CD11b/CD18 plays a novel
      and unsuspected homeostatic role in inflammation by accelerating the programmed
      elimination of extravasated neutrophils.

PMID- 8986724
TI  - The microbial plague continues.

PMID- 8986725
TI  - Live E. coli cells to treat uremia.

PMID- 8986726
TI  - Live E. coli cells to treat uremia.

PMID- 8986727
TI  - Making malaria research bite.

PMID- 8986728
TI  - Live-attenuated HIV vaccines: how safe is safe enough?

PMID- 8986729
TI  - Another way to generate T cells?

PMID- 8986730
TI  - Janus faces of NF-kappa B: neurodestruction versus neuroprotection.

PMID- 8986731
TI  - Utrophin muscles in on the action.

PMID- 8986732
TI  - Give the embryo a chance.

PMID- 8986733
TI  - Seeking the nucleoside transporter.

PMID- 8986734
TI  - Xenotransplanting hepatocytes: the triumph of a cup half full.

PMID- 8986735
TI  - Presenilins, amyloid-beta and Alzheimer's disease.

PMID- 8986736
TI  - Nitric oxide and inflammation: the answer is blowing in the wind.

PMID- 8986737
TI  - Resistance of neonatal monkeys to live attenuated vaccine strains of simian
      immunodeficiency virus.
AB  - A major safety concern of using live-attenuated vaccine strategies against AIDS
      is the potential exposure of neonates or fetuses to vaccine virus from the
      mother. Here we report that high viral loads and disease were observed in only 2
      of 18 neonatal monkeys infected with gene-deleted vaccine strains of simian
      immunodeficiency virus. Pathogenicity was restricted to neonates born to
      unvaccinated mothers, that is, lacking maternal immunity, and that received
      extremely high doses of vaccine virus orally. No in utero transmission of vaccine
      virus was observed in four neonates born to mothers vaccinated during the second
      trimester. Our results suggest that the live attenuated vaccine approach should
      remain a viable option for preventing HIV infection and disease in high-risk
      human populations.

PMID- 8986738
TI  - A new transmissible AIDS-like disease in mice induced by alloimmune stimuli.
AB  - The search for a suitable and reliable animal model for human AIDS that is easy
      to use on a large scale continues. Here we describe a new condition in mice that
      closely resembles human AIDS, namely, chronic lymphoproliferation with dramatic
      depletion of CD4-positive cells, progressive impairment of the immune responses,
      and Kaposi's sarcoma-like tumors or terminal B-lymphomas. The AIDS-like disease
      was primarily induced by mating BALB/c female mice to C57BL/6 males during a 1
      year period (7-10 allogeneic pregnancies) followed by immunization with paternal
      lymphocytes. The disease is sexually and vertically transmissible, transferrable
      by cell-free plasma and is associated with autoimmune reactions to major
      histocompatibility complex antigens and CD4 cells. We hope that this becomes a
      model for studying the mechanisms of AIDS immunopathogenesis and immune-based
      treatment approaches.

PMID- 8986739
TI  - Transcytosis of infectious human immunodeficiency virus across a tight human
      epithelial cell line barrier.
AB  - Contact between various epithelial cell lines and HIV chronically infected
      mononuclear cell lines results in a massive and rapid budding of HIV virions
      toward the epithelium followed by their internalization into epithelial endosome
      like structures. Here it is shown that as early as 30 minutes after apical
      contact, primary virus isolates generated from primary peripheral blood
      leukocytes from HIV-infected patients can cross an epithelial cell line barrier
      using transcytosis, the characteristic epithelial transcellular vesicular
      pathway. As the next step in the spread of infection, transcytosed HIV particles
      can productively infect mononuclear cells located at the basolateral side of the
      epithelial barrier. These observations suggest an alternative, rapid and
      efficient mechanism for transmission of HIV across an intact epithelial barrier.

PMID- 8986741
TI  - Myelination of the canine central nervous system by glial cell transplantation: a
      model for repair of human myelin disease.
AB  - There is a lack of effective means of promoting remyelination of the central
      nervous system (CNS) in humans with chronic demyelinating disease. We have
      investigated the ability of transplanted glia to myelinate areas of the CNS
      equivalent to focal demyelinated lesions in multiple sclerosis (MS). In these
      studies we show that transplantation of oligodendrocytes or their progenitors
      into the CNS of a neonatal or adult canine myelin mutant results in repair of
      large areas similar in size to many MS plaques. Progenitor or pre-progenitor
      cells of the oligodendrocyte lineage have the greatest capacity for myelination
      following grafting, although cells of neonatal origin may also be used. Such an
      approach may therefore have therapeutic value in the repair of focal lesions in
      human myelin disease.

PMID- 8986740
TI  - Reduction of serum cholesterol in Watanabe rabbits by xenogeneic hepatocellular
      transplantation.
AB  - Transplantation of xenogeneic hepatocytes would provide a novel therapy for liver
      disease and would help to solve the problem of an insufficient supply of donor
      organs. We have tested whether xenogeneic cells infused into the liver could
      correct the metabolic defect in the Watanable heritable hyperlipidemic (WHHL)
      rabbit, an animal model for homozygous familial hypercholesterolemia, and we have
      investigated whether the infused cells traverse the lining of the portal
      vasculature. We find that porcine hepatocytes are localized in the hepatic
      sinusoids after surgery and subsequently migrate out of the vessels and integrate
      into the hepatic parenchyma. The integrated porcine hepatocytes provide
      functional LDL receptors that lower serum cholesterol in the WHHL rabbit by 30
      60% for at least 100 days.

PMID- 8986742
TI  - Inositol prevents folate-resistant neural tube defects in the mouse.
AB  - Clinical trials demonstrate that up to 70% of neural tube defects (NTDs) can be
      prevented by folic acid supplementation in early pregnancy, whereas the remaining
      NTDs are resistant to folate. Here, we show that a second vitamin, myo-inositol,
      is capable of significantly reducing the incidence of spinal NTDs in curly tail
      mice, a genetic model of folate-resistant NTDs. Inositol increases flux through
      the inositol/lipid cycle, stimulating protein kinase C activity and upregulating
      expression of retinoic acid receptor beta, specifically in the caudal portion of
      the embryonic hindgut. This reduces the delay in closure of the posterior
      neuropore, the embryonic defect that is known to lead directly to spina bifida in
      curly tail embryos. Our findings reveal a molecular pathway of NTD prevention and
      suggest the possible efficacy of combined treatment with folate and inositol in
      overcoming the majority of human NTDs.

PMID- 8986743
TI  - Mutant presenilins of Alzheimer's disease increase production of 42-residue
      amyloid beta-protein in both transfected cells and transgenic mice.
AB  - The mechanism by which mutations in the presenilin (PS) genes cause the most
      aggressive form of early-onset Alzheimer's disease (AD) is unknown, but
      fibroblasts from mutation carriers secrete increased levels of the amyloidogenic
      A beta 42 peptide, the main component of AD plaques. We established transfected
      cell and transgenic mouse models that coexpress human PS and amyloid beta-protein
      precursor (APP) genes and analyzed quantitatively the effects of PS expression on
      APP processing. In both models, expression of wild-type PS genes did not alter
      APP levels, alpha- and beta-secretase activity and A beta production. In the
      transfected cells, PS1 and PS2 mutations caused a highly significant increase in
      A beta 42 secretion in all mutant clones. Likewise, mutant but not wildtype PS1
      transgenic mice showed significant overproduction of A beta 42 in the brain, and
      this effect was detectable as early as 2-4 months of age. Different PS mutations
      had differential effects on A beta generation. The extent of A beta 42 increase
      did not correlate with presenilin expression levels. Our data demonstrate that
      the presenilin mutations cause a dominant gain of function and may induce AD by
      enhancing A beta 42 production, thus promoting cerebral beta-amyloidosis.

PMID- 8986745
TI  - Aspartate residue 7 in amyloid beta-protein is critical for classical complement
      pathway activation: implications for Alzheimer's disease pathogenesis.
AB  - Fibrillar amyloid beta-protein has been implicated in the pathogenesis of
      Alzheimer's disease because of its neurotoxicity and its ability to activate
      complement. Reactive microglia, astrocytes and complement (C') components
      (reviewed in ref. 6) are associated with senile plaques, the fibrillar, beta
      sheet assemblies of amyloid beta-peptide found predominantly in brain from
      individuals with AD (ref. 7). These indications of inflammatory events are not
      prevalent in the nonfibrillar "diffuse" plaques often seen in age-matched control
      cases without dementia. Clinical studies over the past several years have
      correlated the use of anti-inflammatory drugs with a decrease in the incidence
      and progression of AD dementia and/or dysfunction, supporting a role for gliosis
      and inflammation in AD pathogenesis (reviewed in ref. 6). C5a, a product of C'
      activation, is chemotactic for microglia. Thus, complement activation provides a
      specific mechanism for recruiting reactive glial cells to the site of the
      fibrillar amyloid beta-protein plaque, which could lead to inflammatory events,
      neuronal dysfunction and degeneration. With the use of truncated amyloid beta
      peptides, the region of amyloid beta-protein limited by residues 4 and 11 has
      been identified as critical in the interaction between amyloid beta-protein and
      C1q, the recognition component of the classical complement pathway (CCP), which
      results in the activation of C'. Furthermore, substitution of an isoaspartic acid
      for aspartic acid at amyloid beta-protein residue 7 resulted in the complete
      elimination of CCP-activating activity. A molecular model of this interaction has
      been generated that should be useful in the design of candidate therapeutic
      inhibitors of CCP activation by amyloid beta-protein.

PMID- 8986744
TI  - Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys.
AB  - Apoptosis is a morphologically defined form of programmed cell death seen in a
      variety of circumstances, including immune cell selection, carcinogenesis and
      development. Apoptosis has very recently been seen after ischemic or traumatic
      injury to the central nervous system (CNS), suggesting that active cell death as
      well as passive necrosis may mediate damage after CNS injury. After spinal cord
      injury (SCI) in the rat, typical post-traumatic necrosis occurred, but in
      addition, apoptotic cells were found from 6 hours to 3 weeks after injury,
      especially in the spinal white matter. Apoptotic cells were positive for
      oligodendrocyte markers. After SCI in monkeys, apoptotic cells were found within
      remote degenerating fiber tracts. Both secondary degeneration at the site of SCI
      and the chronic demyelination of tracts away from the injury appear to be due in
      part to apoptosis. As cytokines have been shown to mediate oligodendrocyte death
      in vitro, it seems likely that chronic demyelination after CNS injury shares
      features with chronic degenerative disorders like multiple sclerosis.

PMID- 8986746
TI  - Sterile protection of monkeys against malaria after administration of interleukin
      12.
AB  - An estimated 300-500 million new infections and 1.5-2.7 million deaths attributed
      to malaria occur annually in the developing world, and every year tens of
      millions of travelers from countries where malaria is not transmitted visit
      countries with malaria. Because the parasites that cause malaria have developed
      resistance to many antimalarial drugs, new methods for prevention are required.
      Intraperitoneal injection into mice of one dose of 150 ng (approximately 7.5
      micrograms per kg body weight) recombinant mouse interleukin-12 (rmIL-12) 2 days
      before challenge with Plasmodium yoelii sporozoites protects 100% of mice against
      malaria. We report that one subcutaneous injection of 10 micrograms/kg
      recombinant human IL-12 (rhIL-12) 2 days before challenge with P. cynomolgi
      sporozoites protected seven of seven rhesus monkeys. Protection was associated
      with marked increases in plasma levels of interferon-gamma (IFN-gamma), and
      relative increases of lymphoid cell messenger RNA coding for IFN-gamma and
      several other cytokines. We speculate that rIL-12 protects monkeys through IFN
      gamma-dependent elimination of P. cynomolgi-infected hepatocytes. This first
      report of rIL-12-induced protection of primates against an infectious agent
      supports assessment of rhIL-12 for immunoprophylaxis of human malaria.

PMID- 8986747
TI  - T-cell antigen receptor transmembrane peptides modulate T-cell function and T
      cell-mediated disease.
AB  - This study describes a novel method of inhibiting T-cell function by the use of
      peptides rationally designed from the T-cell antigen receptor (TCR) alpha-chain
      transmembrane sequence involved with TCR receptor assembly. The most effective
      peptide (core peptide, CP) modulating in vitro and in vivo T-cell function
      contained nine amino acids two of which, lysine and arginine, were hydrophilic
      and separated by four hydrophobic amino acids. CP without chemical modification
      or conjugation was able to enter non-T and T cells. Conjugation of CP at the
      carboxyl terminus with palmitic acid resulted in a greater inhibition of T-cell
      interleukin-2 (IL-2) production in vitro than peptide alone. When examined for
      effects in vivo, CP reduced clinical signs of inflammation in three T cell
      mediated disease models including adjuvant-induced arthritis, experimental
      allergic neuritis, and cyclophosphamide-induced diabetes in NOD/Lt(F) mice. This
      peptide or its analogues has potential as a therapeutic agent in human
      inflammatory and autoimmune disorders.

PMID- 8986748
TI  - Cloning of a human nucleoside transporter implicated in the cellular uptake of
      adenosine and chemotherapeutic drugs.
AB  - In most mammalian cells nucleoside uptake occurs primarily via broad-specificity,
      es (e, equilibrative; 5, sensitive to NBMPR inhibition) transporters that are
      potently inhibited by nitrobenzylthioinosine (NBMPR). These transporters are
      essential for nucleotide synthesis by salvage pathways in hemopoietic and other
      cells that lack de novo pathways and are the route of cellular uptake for many
      cytotoxic nucleosides used in cancer and viral chemotherapy. They play an
      important role in adenosine-mediated regulation of many physiological processes,
      including neurotransmission and platelet aggregation, and are a target for
      coronary vasodilator drugs. We have previously reported the purification of the
      prototypic es transporter from human erythrocytes and have shown that this
      glycoprotein of apparent M, 55,000 is immunologically related to nucleoside
      transporters from several other species and tissues, including human placenta.
      Here we report the isolation of a human placental cDNA encoding a 456-residue
      glycoprotein with functional characteristics typical of an es-type transporter.
      It is predicted to possess 11 membrane-spanning regions and is homologous to
      several proteins of unknown function in yeast, nematodes, plants and mammals.
      Because of its central role in the uptake both of adenosine and of
      chemotherapeutic nucleosides, study of this protein should not only provide
      insights into the physiological roles of nucleoside transport but also open the
      way to improved therapies.

PMID- 8986749
TI  - Continuous separations in microfabricated channels for monitoring ultrasmall
      biological environments.

PMID- 8986750
TI  - More sensory competence for nociceptive neurons in culture.

PMID- 8986752
TI  - Equilibration rates in lipid monolayers.
AB  - A theoretical analysis is given for the rate of change of domain sizes in lipid
      monolayers at the air-water interface. The calculation is applicable to liquid
      domains formed from binary mixtures of lipids that form two coexisting liquid
      phases. Under conditions where the two lipid molecules have approximately equal
      areas, the equilibration rate does not involve macroscopic hydrodynamic flow in
      the subphase but rather depends on the diffusion coefficient of the lipid
      molecules. The calculation shows that the equilibration rate in binary mixtures
      of cholesterol and phosphatidylcholine is remarkably slow, the radius of a
      typical 20-microns diameter domain changing by as little as a part in a million
      per second. Under these circumstances, equilibration times of the order of days
      of weeks are expected. Even with such long times, the final state reached by the
      monolayer will in general be a state of metastable equilibrium, rather than true
      equilibrium.

PMID- 8986751
TI  - Positive strands to the rescue again: a segmented negative-strand RNA virus
      derived from cloned cDNAs.

PMID- 8986755
TI  - A synthetic cryIC gene, encoding a Bacillus thuringiensis delta-endotoxin,
      confers Spodoptera resistance in alfalfa and tobacco.
AB  - Spodoptera species, representing widespread polyphagous insect pests, are
      resistant to Bacillus thuringiensis delta-endotoxins used thus far as
      insecticides in transgenic plants. Here we describe the chemical synthesis of a
      cryIC gene by a novel template directed ligation-PCR method. This simple and
      economical method to construct large synthetic genes can be used when routine
      resynthesis of genes is required. Chemically phosphorylated adjacent
      oligonucleotides of the gene to be synthesized are assembled and ligated on a
      single-stranded, partially homologous template derived from a wild-type gene
      (cryIC in our case) by a thermostable pfu DNA ligase using repeated cycles of
      melting, annealing, and ligation. The resulting synthetic DNA strands are
      selectively amplified by PCR with short specific flanking primers that are
      complementary only to the new synthetic DNA. Optimized expression of the
      synthetic cryIC gene in alfalfa and tobacco results in the production of 0.01
      0.2% of total soluble proteins as CryIC toxin and provides protection against the
      Egyptian cotton leafworm (Spodoptera littoralis) and the beet armyworm
      (Spodoptera exigua). To facilitate selection and breeding of Spodoptera-resistant
      plants, the cryIC gene was linked to a pat gene, conferring resistance to the
      herbicide BASTA.

PMID- 8986756
TI  - Regulation of product chain length by isoprenyl diphosphate synthases.
AB  - An analysis of the x-ray structure of homodimeric avian farnesyl diphosphate
      synthase (geranyltransferase, EC 2.5.1.10) coupled with information about
      conserved amino acids obtained from a sequence alignment of 35 isoprenyl
      diphosphate synthases that synthesize farnesyl (C15), geranylgeranyl (C20), and
      higher chain length isoprenoid diphosphates suggested that the side chains of
      residues corresponding to F112 and F113 in the avian enzyme were important for
      determining the ultimate length of the hydrocarbon chains. This hypothesis was
      supported by site-directed mutagenesis to transform wild-type avian farnesyl
      diphosphate synthase (FPS) into synthases capable of producing geranylgeranyl
      diphosphate (F112A), geranylfarnesyl (C25) diphosphate (F113S), and longer chain
      prenyl diphosphates (F112A/F113S). An x-ray analysis of the structure of the
      F112A/F113S mutant in the apo state and with allylic substrates bound produced
      the strongest evidence that these mutations caused the observed change in product
      specificity by directly altering the size of the binding pocket for the growing
      isoprenoid chain in the active site of the enzyme. The proposed binding pocket in
      the apo mutant structure was increased in depth by 5.8 A as compared with that
      for the wild-type enzyme. Allylic diphosphates were observed in the holo
      structures, bound through magnesium ions to the aspartates of the first of two
      conserved aspartate-rich sequences (D117-D121), with the hydrocarbon tails of all
      the ligands growing down the hydrophobic pocket toward the mutation site. A model
      was constructed to show how the growth of a long chain prenyl product may proceed
      by creation of a hydrophobic passageway from the FPS active site to the outside
      surface of the enzyme.

PMID- 8986757
TI  - Chaperone activity and structure of monomeric polypeptide binding domains of
      GroEL.
AB  - The chaperonin GroEL is a large complex composed of 14 identical 57-kDa subunits
      that requires ATP and GroES for some of its activities. We find that a monomeric
      polypeptide corresponding to residues 191 to 345 has the activity of the
      tetradecamer both in facilitating the refolding of rhodanese and cyclophilin A in
      the absence of ATP and in catalyzing the unfolding of native barnase. Its crystal
      structure, solved at 2.5 A resolution, shows a well-ordered domain with the same
      fold as in intact GroEL. We have thus isolated the active site of the complex
      allosteric molecular chaperone, which functions as a "minichaperone." This has
      mechanistic implications: the presence of a central cavity in the GroEL complex
      is not essential for those representative activities in vitro, and neither are
      the allosteric properties. The function of the allosteric behavior on the binding
      of GroES and ATP must be to regulate the affinity of the protein for its various
      substrates in vivo, where the cavity may also be required for special functions.

PMID- 8986758
TI  - Kinetic and structural analysis of mutant CD4 receptors that are defective in HIV
      gp120 binding.
AB  - The T-cell antigen coreceptor CD4 also serves as the receptor for the envelope
      glycoprotein gp120 of HIV. Extensive mutational analysis of CD4 has implicated
      residues from a portion of the extracellular amino-terminal domain (D1) in gp120
      binding. However, none of these proteins has been fully characterized
      biophysically, and thus the precise effects on molecular structure and binding
      interactions are unknown. In the present study, we produced soluble versions of
      three mutant CD4 molecules (F43V, G47S, and A55F) and characterized their
      structural properties, thermostability, and ability to bind gp120.
      Crystallographic and thermodynamic analysis showed minimal structural alterations
      in the F43V and G47S mutant proteins, which have solvent-exposed mutant side
      chains. In contrast, some degree of disorder appears to exist in the folded state
      of A55F, as a result of mutating a buried side chain. Real time kinetic
      measurements of the interaction of the mutant proteins with gp120 showed affinity
      decreases of 5-fold for G47S, 50-fold for A55F, and 200-fold for F43V. Although
      both rate constants for the binding reaction were affected by these mutations,
      the loss in affinity was mainly due to a decrease in on rates, with less drastic
      changes occurring in the off rates. These observations suggest the involvement of
      conformational adaptation in the CD4-gp120 interaction. Together, the structural
      and kinetic data confirm that F43V is a critical residue in gp120 recognition
      site, which may also include main chain interactions at residue Gly-47.

PMID- 8986759
TI  - Methionine residues as endogenous antioxidants in proteins.
AB  - Cysteine and methionine are the two sulfur-containing residues normally found in
      proteins. Cysteine residues function in the catalytic cycle of many enzymes, and
      they can form disulfide bonds that contribute to protein structure. In contrast,
      the specific functions of methionine residues are not known. We propose that
      methionine residues constitute an important antioxidant defense mechanism. A
      variety of oxidants react readily with methionine to form methionine sulfoxide,
      and surface exposed methionine residues create an extremely high concentration of
      reactant, available as an efficient oxidant scavenger. Reduction back to
      methionine by methionine sulfoxide reductases would allow the antioxidant system
      to function catalytically. The effect of hydrogen peroxide exposure upon
      glutamine synthetase from Escherichia coli was studied as an in vitro model
      system. Eight of the 16 methionine residues could be oxidized with little effect
      on catalytic activity of the enzyme. The oxidizable methionine residues were
      found to be relatively surface exposed, whereas the intact residues were
      generally buried within the core of the protein. Furthermore, the susceptible
      residues were physically arranged in an array that guarded the entrance to the
      active site.

PMID- 8986760
TI  - Ferredoxin and ferredoxin-heme maquettes.
AB  - A 16-amino acid residue peptide derived from a consensus motif of natural
      ferredoxins incorporates a tetranuclear iron sulfur cluster under physiological
      conditions. Successful assembly of the [4Fe-4S]2+/1+ cluster within a monomeric
      peptide was demonstrated using size exclusion chromatography, UV-visible, visible
      CD, and cryogenic EPR spectroscopies. The robustness of [4Fe-4S]2+/1+ formation
      was tested using peptides with either the ligating cysteine exchanged for alanine
      or with the intervening amino acids replaced by glycine. The small size of the
      peptide allows for modular incorporation into more complex protein structures. In
      one larger structure, we describe a tetra-alpha-helix bundle that self-assembles
      both iron-sulfur clusters and hemes, thereby demonstrating feasibility for the
      general synthesis of maquettes containing multiple, juxtaposed redox cofactors.
      This is a motif common to the catalytic sites of native oxidoreductases.

PMID- 8986761
TI  - Amphipols: polymers that keep membrane proteins soluble in aqueous solutions.
AB  - Amphipols are a new class of surfactants that make it possible to handle membrane
      proteins in detergent-free aqueous solution as though they were soluble proteins.
      The strongly hydrophilic backbone of these polymers is grafted with hydrophobic
      chains, making them amphiphilic. Amphipols are able to stabilize in aqueous
      solution under their native state four well-characterized integral membrane
      proteins: (i) bacteriorhodopsin, (ii) a bacterial photosynthetic reaction center,
      (iii) cytochrome b6f, and (iv) matrix porin.

PMID- 8986762
TI  - Inhibiting transthyretin amyloid fibril formation via protein stabilization.
AB  - Transthyretin (TTR) amyloid fibril formation is observed systemically in familial
      amyloid polyneuropathy and senile systemic amyloidosis and appears to be the
      causative agent in these diseases. Herein, we demonstrate conclusively that
      thyroxine (10.8 microM) inhibits TTR fibril formation efficiently in vitro and
      does so by stabilizing the tetramer against dissociation and the subsequent
      conformational changes required for amyloid fibril formation. In addition, the
      nonnative ligand 2,4,6-triiodophenol, which binds to TTR with slightly increased
      affinity also inhibits TTR fibril formation by this mechanism. Sedimentation
      velocity experiments were employed to show that TTR undergoes dissociation
      (linked to a conformational change) to form the monomeric amyloidogenic
      intermediate, which self-assembles into amyloid in the absence, but not in the
      presence of thyroxine. These results demonstrate the feasibility of using small
      molecules to stabilize the native fold of a potentially amyloidogenic human
      protein, thus preventing the conformational changes, which appear to be the
      common link in several human amyloid diseases. This strategy and the compounds
      resulting from further development should prove useful for critically evaluating
      the amyloid hypothesis--i.e., the putative cause-and-effect relationship between
      TTR amyloid deposition and the onset of familial amyloid polyneuropathy and
      senile systemic amyloidosis.

PMID- 8986763
TI  - Purification of the beta-cell glucose-sensitive factor that transactivates the
      insulin gene differentially in normal and transformed islet cells.
AB  - The beta cell-specific glucose-sensitive factor (GSF), which binds the A3 motif
      of the rat I and human insulin promoters, is modulated by extracellular glucose.
      A single mutation in the GSF binding site of the human insulin promoter abolishes
      the stimulation by high glucose only in normal islets, supporting the suggested
      physiological role of GSF in the glucose-regulated expression of the insulin
      gene. GSF binding activity was observed in all insulin-producing cells. We have
      therefore purified this activity from the rat insulinoma RIN and found that a
      single polypeptide of 45 kDa was responsible for DNA binding. Its amino acid
      sequence, determined by microsequencing, provided direct evidence that GSF
      corresponds to insulin promoter factor 1 (IPF-1; also known as PDX-1) and that,
      in addition to its essential roles in development and differentiation of
      pancreatic islets and in beta cell-specific gene expression, it functions as
      mediator of the glucose effect on insulin gene transcription in differentiated
      beta cells. The human cDNA coding for GSF/IPF-1 has been cloned, its cell and
      tissue distribution is described. Its expression in the glucagon-producing cell
      line alpha TC1 transactivates the wild-type human insulin promoter more
      efficiently than the mutated construct. It is demonstrated that high levels of
      ectopic GSF/IPF-1 inhibit the expression of the human insulin gene in normal
      islets, but not in transformed beta TC1 cells. These results suggest the
      existence of a control mechanism, such as requirement for a coactivator of
      GSF/IPF-1, which may be present in limiting amounts in normal as opposed to
      transformed beta cells.

PMID- 8986764
TI  - Synthesis and biological activity of DNA damaging agents that form decoy binding
      sites for the estrogen receptor.
AB  - It is a goal of cancer chemotherapy to achieve the selective killing of tumor
      cells while minimizing toxicity to normal tissues. We describe the design of
      selective toxins forming DNA adducts that attract the estrogen receptor (ER), a
      transcription factor that is overexpressed in many human breast and ovarian
      tumors. The compounds consist of 4-(3-aminopropyl)-N,N-(2-chloroethyl)-aniline
      linked to 2-(4'-hydroxyphenyl)-3-methyl-5-hydroxy-indole. The former moiety is a
      DNA damaging nitrogen mustard and the latter is a ligand for the ER. The
      connection between these groups was refined to permit DNA adducts formed by the
      mustard portion of the molecule to present the ligand domain so that it was able
      to interact efficiently with the ER. By using 16-mers containing specific DNA
      adducts, it was determined that monoadducts and putative intrastrand crosslinks
      were preferred targets for the ER over interstrand crosslinks. A series of
      structurally related 2-phenylindole mustards was prepared, some of which were
      selectively toxic to the ER-positive breast cancer cell line MCF-7, as compared
      with the ER(-) negative line MDA-MB231. The ability both to bind to DNA and to
      interact significantly with the ER were essential to achieve selective lethality
      toward ER(+) cells. Compounds forming DNA adducts without the ability to bind
      receptor showed similar toxicities in the two cell lines. Several models could
      explain the selective toxicity of the mustard-phenylindole compounds toward ER(+)
      cells. The favored model suggests that a mustard-DNA adduct is shielded by the ER
      from DNA repair enzymes and hence cells possessing an abundance of the ER
      selectively retain the adduct and are killed.

PMID- 8986765
TI  - Peroxynitrite, the coupling product of nitric oxide and superoxide, activates
      prostaglandin biosynthesis.
AB  - Peroxynitrite activates the cyclooxygenase activities of constitutive and
      inducible prostaglandin endoperoxide synthases by serving as a substrate for the
      enzymes' peroxidase activities. Activation of purified enzyme is induced by
      direct addition of peroxynitrite or by in situ generation of peroxynitrite from
      NO coupling to superoxide anion. Cu,Zn-superoxide dismutase completely inhibits
      cyclooxygenase activation in systems where peroxynitrite is generated in situ
      from superoxide. In the murine macrophage cell line RAW264.7, the lipophilic
      superoxide dismutase-mimetic agents, Cu(II) (3,5-diisopropylsalicylic acid)2, and
      Mn(III) tetrakis(1-methyl-4-pyridyl)porphyrin dose-dependently decrease the
      synthesis of prostaglandins without affecting the levels of NO synthase or
      prostaglandin endoperoxide synthase or by inhibiting the release of arachidonic
      acid. These findings support the hypothesis that peroxynitrite is an important
      modulator of cyclooxygenase activity in inflammatory cells and establish that
      superoxide anion serves as a biochemical link between NO and prostaglandin
      biosynthesis.

PMID- 8986766
TI  - The ATM homologue MEC1 is required for phosphorylation of replication protein A
      in yeast.
AB  - Replication protein A (RPA) is a highly conserved single-stranded DNA-binding
      protein, required for cellular DNA replication, repair, and recombination. In
      human cells, RPA is phosphorylated during the S and G2 phases of the cell cycle
      and also in response to ionizing or ultraviolet radiation. Saccharomyces
      cerevisiae exhibits a similar pattern of cell cycle-regulated RPA
      phosphorylation, and our studies indicate that the radiation-induced reactions
      occur in yeast as well. We have examined yeast RPA phosphorylation during the
      normal cell cycle and in response to environmental insult, and have demonstrated
      that the checkpoint gene MEC1 is required for the reaction under all conditions
      tested. Through examination of several checkpoint mutants, we have placed RPA
      phosphorylation in a novel pathway of the DNA damage response. MEC1 is similar in
      sequence to human ATM, the gene mutated in patients with ataxia-telangiectasia (A
      T). A-T cells are deficient in multiple checkpoint pathways and are
      hypersensitive to killing by ionizing radiation. Because A-T cells exhibit a
      delay in ionizing radiation-induced RPA phosphorylation, our results indicate a
      functional similarity between MEC1 and ATM, and suggest that RPA phosphorylation
      is involved in a conserved eukaryotic DNA damage-response pathway defective in A
      T.

PMID- 8986767
TI  - Architectural limits on split genes.
AB  - Exon/intron architecture varies across the eukaryotic kingdom with large introns
      and small exons the rule in vertebrates and the opposite in lower eukaryotes. To
      investigate the relationship between exon and intron size in pre-mRNA processing,
      internally expanded exons were placed in vertebrate genes with small and large
      introns. Both exon and intron size influenced splicing phenotype. Intron size
      dictated if large exons were efficiently recognized. When introns were large,
      large exons were skipped; when introns were small, the same large exons were
      included. Thus, large exons were incompatible for splicing if and only if they
      were flanked by large introns. Both intron and exon size became problematic at
      approximately 500 nt, although both exon and intron sequence influenced the size
      at which exons and introns failed to be recognized. These results indicate that
      present-day gene architecture reflects at least in part limitations on exon
      recognition. Furthermore, these results strengthen models that invoke pairing of
      splice sites during recognition of pre-mRNAs, and suggest that vertebrate
      consensus sequences support pairing across either introns or exons.

PMID- 8986768
TI  - Identification of a novel selD homolog from eukaryotes, bacteria, and archaea: is
      there an autoregulatory mechanism in selenocysteine metabolism?
AB  - Escherichia coli selenophosphate synthetase (SPS, the selD gene product)
      catalyzes the production of monoselenophosphate, the selenium donor compound
      required for synthesis of selenocysteine (Sec) and seleno-tRNAs. We report the
      molecular cloning of human and mouse homologs of the selD gene, designated Sps2,
      which contains an in-frame TGA codon at a site corresponding to the enzyme's
      putative active site. These sequences allow the identification of selD gene
      homologs in the genomes of the bacterium Haemophilus influenzae and the archaeon
      Methanococcus jannaschii, which had been previously misinterpreted due to their
      in-frame TGA codon. Sps2 mRNA levels are elevated in organs previously implicated
      in the synthesis of selenoproteins and in active sites of blood cell development.
      In addition, we show that Sps2 mRNA is up-regulated upon activation of T
      lymphocytes and have mapped the Sps2 gene to mouse chromosome 7. Using the mouse
      gene isolated from the hematopoietic cell line FDCPmixA4, we devised a construct
      for protein expression that results in the insertion of a FLAG tag sequence at
      the N terminus of the SPS2 protein. This strategy allowed us to document the
      readthrough of the in-frame TGA codon and the incorporation of 75Se into SPS2.
      These results suggest the existence of an autoregulatory mechanism involving the
      incorporation of Sec into SPS2 that might be relevant to blood cell biology. This
      mechanism is likely to have been present in ancient life forms and conserved in a
      variety of living organisms from all domains of life.

PMID- 8986769
TI  - Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling.
AB  - Interferon gamma (IFN-gamma) induces rapid tyrosine phosphorylation of the latent
      cytoplasmic transcription factor, Stat1, which then forms homodimers,
      translocates to the nucleus and participates in IFN-gamma-induced transcription.
      However, little is known of the interactions between Stat1 and the general
      transcription machinery during transcriptional activation. We show here that
      Stat1 can directly interact with the CREB-binding protein (CBP)/p300 family of
      transcriptional coactivators. Specifically, two interaction regions were
      identified: the amino-terminal region of Stat1 interacts with the CREB-binding
      domain of CBP/p300 and the carboxyl-terminal region of Stat1 interacts with the
      domain of CBP/p300 that binds adenovirus E1A protein. Transfection experiments
      suggest a role for these interactions in IFN-gamma-induced transcription. Because
      CBP/p300-binding is required for the adenovirus E1A protein to regulate
      transcription of many genes during viral replication and cellular transformation,
      it is possible that the anti-viral effect of IFN-gamma is based at least in part
      on direct competition by nuclear Stat1 with E1A for CBP/p300 binding.

PMID- 8986770
TI  - Similar DNA recognition properties of alternatively spliced Drosophila POU
      factors.
AB  - The POU-IV or "Brn-3" class of POU-domain transcription factors is represented in
      Drosophila by I-POU and twin-of-I-POU, alternative splice products of the I-POU
      gene. I-POU has been previously reported to inhibit DNA binding by the POU-III
      class factor drifter/Cf1a via the formation of heterodimeric complexes. Here we
      report that expression of the I-POU/tI-POU message is maximal late in the
      embryonic phase of Drosophila development, and I-POU is the preferred splice
      variant. Although I-POU lacks two basic amino acid residues in the POU
      homeodomain found in tI-POU and Brn-3.0, these three POU-IV class proteins
      exhibit very similar DNA-binding specificity. In contrast to previously published
      reports, the results presented here show no effect of I-POU on DNA binding by
      drifter, and no evidence for I-POU/drifter dimerization. These results suggest
      that the I-POU/tI-POU gene products function by transcriptional mechanisms
      similar to those of the homologous POU-IV class factors expressed in other
      species, not by unique inhibitory mechanism.

PMID- 8986771
TI  - Mutagenesis associated with nitric oxide production in transgenic SJL mice.
AB  - We recently reported development of an experimental model for the study of nitric
      oxide (NO.) toxicology in vivo. SJL mice were injected with superantigen-bearing
      RcsX (pre-B-cell lymphoma) cells, which migrated to the spleen and lymph nodes,
      where their rapid growth induced activation of macrophages to produce large
      amounts of NO. over a period of several weeks. In the experiments described here,
      we used this model to investigate mutagenesis in splenocytes exposed to NO.
      during RcsX cell growth. Transgenic mice were produced by crossbreeding animals
      of the pUR288 transgenic C57BL/6 and SJL strains. RcsX cells were injected into
      F1 mice and NO. production was confirmed by quantification of urinary nitrate,
      the ultimate metabolite of NO. Mutant frequency in the lacZ gene of the pUR288
      plasmid was determined in DNA isolated from spleen (target) and kidney
      (nontarget) tissues. A significant elevation in mutant frequency was found in the
      spleen, but not in the kidney, of tumor-bearing mice. Furthermore, increases in
      mutant frequency in the spleen as well as NO. production were abrogated by
      administration of N-methylarginine, a NO. inhibitor, to mice following injection
      of RcsX cells. These results indicate that NO. had mutagenic activity in RcsX
      tumor-bearing mice and thus support a possible role for its involvement in the
      carcinogenic process.

PMID- 8986772
TI  - Direct interaction of flagellin termini essential for polymorphic ability of
      flagellar filament.
AB  - We report the structures of flagellar filaments reconstituted from various
      flagellins with small terminal truncations. Flagellins from Salmonella
      typhimurium strains SJW1103 (wild type), SJW1660, and SJW1655 were used, which
      form a left-handed supercoil, the L- and R-type straight forms, respectively.
      Structure analyses were done by electron cryomicroscopy and helical image
      reconstruction with a help of x-ray fiber diffraction for determining precise
      helical symmetries. Truncation of either terminal region, irrespective of the
      original flagellin species, results in a straight filament having a helical
      symmetry distinct either from the L- or R-type. This filament structure is named
      Lt-type. Although the local subunit packing is similar in all three types, a
      close comparison shows that the Lt-type packing is almost identical to the R-type
      but distinct from the L-type, which demonstrates the strong two-state preference
      of the subunit interactions. The structure clearly suggests that both termini are
      located in the inner tube of the concentric double-tubular structure of the
      filament core, and their proper interaction is responsible for the correct
      folding of fairly large terminal regions that form the inner tube. The double
      tubular structure appears to be essential for the polymorphic ability of
      flagellar filaments, which is required for the swimming-tumbling of bacterial
      taxis.

PMID- 8986773
TI  - Determination of the lifetime and force dependence of interactions of single
      bonds between surface-attached CD2 and CD48 adhesion molecules.
AB  - We studied single molecular interactions between surface-attached rat CD2, a T
      lymphocyte adhesion receptor, and CD48, a CD2 ligand found on antigen-presenting
      cells. Spherical particles were coated with decreasing densities of CD48-CD4
      chimeric molecules then driven along CD2-derivatized glass surfaces under a low
      hydrodynamic shear rate. Particles exhibited multiple arrests of varying
      duration. By analyzing the dependence of arrest frequency and duration on the
      surface density of CD48 sites, it was concluded that (i) arrests were generated
      by single molecular bonds and (ii) the initial bond dissociation rate was about
      7.8 s-1. The force exerted on bonds was increased from about 11 to 22 pN; the
      detachment rate exhibited a twofold increase. These results agree with and extend
      studies on the CD2-CD48 interaction by surface plasmon resonance technology,
      which yielded an affinity constant of approximately 10(4) M-1 and a dissociation
      rate of > or = 6 s-1. It is concluded that the flow chamber technology can be an
      useful complement to atomic force microscopy for studying interactions between
      isolated biomolecules, with a resolution of about 20 ms and sensitivity of a few
      piconewtons. Further, this technology might be extended to actual cells.

PMID- 8986774
TI  - The photoisomerization of retinal in bacteriorhodospin: experimental evidence for
      a three-state model.
AB  - The primary events in the all-trans to 13-cis photoisomerization of retinal in
      bacteriorhodopsin have been investigated with femtosecond time-resolved
      absorbance spectroscopy. Spectra measured over a broad range extending from 7000
      to 22,400 cm-1 reveal features whose dynamics are inconsistent with a model
      proposed earlier to account for the highly efficient photoisomerization process.
      Emerging from this work is a new three-state model. Photoexcitation of retinal
      with visible light accesses a shallow well on the excited state potential energy
      surface. This well is bounded by a small barrier, arising from an avoided
      crossing that separates the Franck-Condon region from the nearby reactive region
      of the photoisomerization coordinate. At ambient temperatures, the reactive
      region is accessed with a time constant of approximately 500 fs, whereupon the
      retinal rapidly twists and encounters a second avoided crossing region. The
      protein mediates the passage into the second avoided crossing region and thereby
      exerts control over the quantum yield for forming 13-cis retinal. The driving
      force for photoisomerization resides in the retinal, not in the surrounding
      protein. This view contrasts with an earlier model where photoexcitation was
      thought to access directly a reactive region of the excited-state potential and
      thereby drive the retinal to a twisted conformation within 100-200 fs.

PMID- 8986776
TI  - Red blood cell adhesion on a solid/liquid interface.
AB  - Red blood cells (RBCs), previously fixed with glutaraldehyde, adhere to glass
      slides coated with fibrinogen. The RBC deposition process on the horizontal glass
      surface is investigated by analyzing the relative surface covered by the RBCs, as
      well as the variance of this surface coverage, as a function of the concentration
      of particles. This study is performed by optical microscopy and image analysis. A
      model, derived from the classical random sequential adsorption model, has been
      developed to account for the experimental results. This model highlights the
      strong influence of the hydrodynamic interactions during the deposition process.

PMID- 8986775
TI  - Effect of beta-amyloid block of the fast-inactivating K+ channel on intracellular
      Ca2+ and excitability in a modeled neuron.
AB  - beta-Amyloid peptide (A beta), one of the primary protein components of senile
      plaques found in Alzheimer disease, is believed to be toxic to neurons by a
      mechanism that may involve loss of intracellular calcium regulation. We have
      previously shown that A beta blocks the fast-inactivating potassium (A) current.
      In this work, we show, through the use of a mathematical model, that the A beta
      mediated block of the A current could result in increased intracellular calcium
      levels and increased membrane excitability, both of which have been observed in
      vitro upon acute exposure to A beta. Simulation results are compared with
      experimental data from the literature; the simulations quantitatively capture the
      observed concentration dependence of the neuronal response and the level of
      increase in intracellular calcium.

PMID- 8986777
TI  - Spectral diffusion and the energy landscape of a protein.
AB  - We present a novel type of spectral diffusion experiment in the millikelvin range
      to characterize the energy landscape of a protein as compared with that of a
      glass. We measure the time evolution of spectral holes for more than 300 hr after
      well-defined initial nonequilibrium conditions. We show that the model of
      noninteracting two-level systems can describe spectral diffusion in the glass,
      but fails for the protein. Our results further demonstrate that randomness in the
      energy landscape of a protein shows features of organization. There are "deep
      minimum" states separated by barriers, the heights of which we are able to
      estimate. The energy landscape of a glass is featureless by comparison.

PMID- 8986778
TI  - Identification of fission yeast nuclear markers using random polypeptide fusions
      with green fluorescent protein.
AB  - We describe a method for identifying genes encoding proteins with stereospecific
      intracellular localizations in the fission yeast Schizosaccharomyces pombe. Yeast
      are transformed with a gene library in which S. pombe genomic sequences are fused
      to the gene encoding the Aequorea victoria green fluorescent protein (GFP), and
      intracellular localizations are subsequently identified by rapid fluorescence
      screening in vivo. In a model application of these methods to the fission yeast
      nucleus, we have identified several novel genes whose products are found in
      specific nuclear regions, including chromatin, the nucleolus, and the mitotic
      spindle, and sequence similarities between some of these genes and previously
      identified genes encoding nuclear proteins have validated the approach. These
      methods will be useful in identifying additional components of the S. pombe
      nucleus, and further extensions of this approach should also be applicable to a
      more comprehensive identification of the elements of intracellular architecture
      in fission yeast.

PMID- 8986779
TI  - Androgen-repressed phenotype in human prostate cancer.
AB  - An androgen-repressed human prostate cancer cell line, ARCaP, was established and
      characterized. This cell line was derived from the ascites fluid of a patient
      with advanced metastatic disease. In contrast to the behavior of androgen
      dependent LNCaP and its androgen-independent C4-2 subline, androgen and estrogen
      suppress the growth of ARCaP cells in a dose-dependent manner in vivo and in
      vitro. ARCaP is tumorigenic and highly metastatic. It metastasizes to the lymph
      node, lung, pancreas, liver, kidney, and bone, and forms ascites fluid in athymic
      hosts. ARCaP cells express low levels of androgen receptor mRNA and prostate
      specific antigen mRNA and protein. Immunohistochemical staining shows that ARCaP
      cells stain intensely for epidermal growth factor receptor, c-erb B2/neu, and c
      erb B3. Staining is negative for chromogranin A and positive for bombesin,
      serotonin, neuron-specific enolase, and the c-met protooncogene (a hepatic growth
      factor/scatter factor receptor). ARCaP cells also secrete high levels of
      gelatinase A and B and some stromelysin, which suggests that this cell line may
      contain markers representing invasive adenocarcinoma with selective
      neuronendocrine phenotypes. Along with its repression of growth, androgen is also
      found to repress the expression of prostate-specific antigen in ARCaP cells as
      detected by a prostate-specific antigen promoter-beta-galactosidase reporter
      assay. Our results suggest that the androgen-repressed state may be central to
      prostate cancer progression and that advanced prostate cancer can progress from
      an androgen-independent to an androgen-repressed state.

PMID- 8986780
TI  - The aphid transmission factor of cauliflower mosaic virus forms a stable complex
      with microtubules in both insect and plant cells.
AB  - We analyzed the distribution of the cauliflower mosaic virus (CaMV) aphid
      transmission factor (ATF), produced via a baculovirus recombinant, within Sf9
      insect cells. Immunogold labeling revealed that the ATF colocalizes with an
      atypical cytoskeletal network. Detailed observation by electron microscopy
      demonstrated that this network was composed of microtubules decorated with
      paracrystalline formations, characteristic of the CaMV ATF. A derivative mutant
      of the ATF, unable to self-assemble into paracrystals, was also analyzed. This
      mutant formed a net-like structure, with a mesh of four nanometers, tightly
      sheathing microtubules. Both the ATF- and the derivative mutant-microtubule
      complexes were highly stable. They resisted dilution-, cold-, and calcium-induced
      microtubule disassembly as well as a combination of all three for over 6 hr. CaMV
      ATF cosedimented with microtubules and, surprisingly, it bound to Taxol
      stabilized microtubules at high ionic strength, thus suggesting an atypical
      interaction when compared with that usually described for microtubule-binding
      proteins. Using immunofluorescence double labeling we also demonstrated that the
      CaMV ATF colocalizes with the microtubule network when expressed in plant cells.

PMID- 8986781
TI  - Effect of genetic background on the contribution of New Zealand black loci to
      autoimmune lupus nephritis.
AB  - Autoimmune diseases such as systemic lupus erythematosus are complex genetic
      traits with contributions from major histocompatibility complex (MHC) genes and
      multiple unknown non-MHC genes. Studies of animal models of lupus have provided
      important insight into the immunopathogenesis of disease, and genetic analyses of
      these models overcome certain obstacles encountered when studying human patients.
      Genome-wide scans of different genetic crosses have been used to map several
      disease-linked loci in New Zealand hybrid mice. Although some consensus exists
      among studies mapping the New Zealand Black (NZB) and New Zealand White (NZW)
      loci that contribute to lupus-like disease, considerable variability is also
      apparent. A variable in these studies is the genetic background of the non
      autoimmune strain, which could influence genetic contributions from the affected
      strain. A direct examination of this question was undertaken in the present study
      by mapping NZB nephritis-linked loci in backcrosses involving different non
      autoimmune backgrounds. In a backcross with MHC-congenic C57BL/6J mice, H2z
      appeared to be the strongest genetic determinant of severe lupus nephritis,
      whereas in a backcross with congenic BALB/cJ mice, H2z showed no influence on
      disease expression. NZB loci on chromosomes 1, 4, 11, and 14 appeared to
      segregate with disease in the BALB/cJ cross, but only the influence of the
      chromosome 1 locus spanned both crosses and showed linkage with disease when all
      mice were considered. Thus, the results indicate that contributions from disease
      susceptibility loci, including MHC, may vary markedly depending on the non
      autoimmune strain used in a backcross analysis. These studies provide insight
      into variables that affect genetic heterogeneity and add an important dimension
      of complexity for linkage analyses of human autoimmune disease.

PMID- 8986782
TI  - Insulin-stimulated translocation of GLUT4 glucose transporters requires SNARE
      complex proteins.
AB  - A major physiological role of insulin is the regulation of glucose uptake into
      skeletal and cardiac muscle and adipose tissue, mediated by an insulin-stimulated
      translocation of GLUT4 glucose transporters from an intracellular vesicular pool
      to the plasma membrane. This process is similar to the regulated docking and
      fusion of vesicles in neuroendocrine cells, a process that involves SNARE-complex
      proteins. Recently, several SNARE proteins were found in adipocytes: vesicle
      associated membrane protein (VAMP-2), its related homologue cellubrevin, and
      syntaxin-4. In this report we show that treatment of permeabilized 3T3-L1
      adipocytes with botulinum neurotoxin D, which selectively cleaves VAMP-2 and
      cellubrevin, inhibited the ability of insulin to stimulate translocation of GLUT4
      vesicles to the plasma membrane. Furthermore, treatment of the permeabilized
      adipocytes with glutathione S-transferase fusion proteins encoding soluble forms
      of VAMP-2 or syntaxin-4 also effectively blocked insulin-regulated GLUT4
      translocation. These results provide evidence of a functional role for SNARE
      complex proteins in insulin-stimulated glucose uptake and suggest that adipocytes
      utilize a mechanism of regulating vesicle docking and fusion analogous to that
      found in neuroendocrine tissues.

PMID- 8986783
TI  - Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic-nuclear
      transport.
AB  - The product of the c-abl protooncogene is a nonreceptor tyrosine kinase found in
      both the cytoplasm and the nucleus. We report herein that cell adhesion regulates
      the kinase activity and subcellular localization of c-Abl. When fibroblastic
      cells are detached from the extracellular matrix, kinase activity of both
      cytoplasmic and nuclear c-Abl decreases, but there is no detectable alteration in
      the subcellular distribution. Upon adhesion to the extracellular matrix protein
      fibronectin, a transient recruitment of a subset of c-Abl to early focal contacts
      is observed coincident with the export of c-Abl from the nucleus to the
      cytoplasm. The cytoplasmic pool of c-Abl is reactivated within 5 min of adhesion,
      but the nuclear c-Abl is reactivated after 30 min, correlating closely with its
      return to the nucleus and suggesting that the active nuclear c-Abl originates in
      the cytoplasm. In quiescent cells where nuclear c-Abl activity is low, the
      cytoplasmic c-Abl is similarly regulated by adhesion but the nuclear c-Abl is not
      activated upon cell attachment. These results show that c-Abl activation requires
      cell adhesion and that this tyrosine kinase can transmit integrin signals to the
      nucleus where it may function to integrate adhesion and cell cycle signals.

PMID- 8986784
TI  - Estrogen-induced transcription of the progesterone receptor gene does not
      parallel estrogen receptor occupancy.
AB  - The activation of the silent endogenous progesterone receptor (PR) gene by 17
      beta-estradiol (E2) in cells stably transfected with estrogen receptor (ER) was
      used as a model system to study the mechanism of E2-induced transcription. The
      time course of E2-induced PR transcription rate was determined by nuclear run-on
      assays. No marked effect on specific PR gene transcription rates was detected at
      0 and 1 h of E2 treatment. After 3 h of E2 treatment, the PR mRNA synthesis rate
      increased 2.0- +/- 0.2-fold and continued to increase to 3.5- +/- 0.4-fold by 24
      h as compared with 0 h. The transcription rate increase was followed by PR mRNA
      accumulation. No PR mRNA was detectable at 0, 1, and 3 h of E2 treatment. PR mRNA
      accumulation was detected at 6 h of E2 treatment and continued to accumulate
      until 18 h, the longest time point examined. Interestingly, this slow and gradual
      transcription rate increase of the endogenous PR gene did not parallel binding of
      E2 to ER, which was maximized within 30 min. Furthermore, the E2-ER level was
      down-regulated to 15% at 3 h as compared with 30 min of E2 treatment and remained
      low at 24 h of E2 exposure. These paradoxical observations indicate that E2
      induced transcription activation is more complicated than just an association of
      the occupied ER with the transcription machinery.

PMID- 8986785
TI  - Modulation of the chaperone-like activity of bovine alpha-crystallin.
AB  - The effects of pantethine, glutathione, and selected chemical reagents on the
      anti-aggregation activity of alpha-crystallin was evaluated. Protein aggregation
      was monitored by light scattering of solutions of denatured beta L-crystallin or
      alcohol dehydrogenase (ADH). The ratios of beta L-crystallin/alpha-crystallin and
      ADH/alpha-crystallin were adjusted so that partial inhibition of protein
      aggregation at 60 degrees C or 37 degrees C, respectively, was observed and
      modulation of the chaperone action of alpha-crystallin could be evaluated easily
      with selected endogenous metabolites. Enhancement of the anti-aggregation
      activity in the beta L-crystallin assay was strongest with pantethine, which
      appeared to interact with alpha-crystallin. Enhancement of the anti-aggregation
      activity in the ADH assay was strongest with glutathione which appeared to
      interact with ADH. The results indicated that the products of common metabolic
      pathways can modulate the chaperone-like effects of alpha-crystallin on protein
      aggregation.

PMID- 8986786
TI  - Cytoplasmically sequestered wild-type p53 protein in neuroblastoma is relocated
      to the nucleus by a C-terminal peptide.
AB  - Cytoplasmic sequestration of wild-type p53 protein occurs in a subset of primary
      human tumors including breast cancer, colon cancer, and neuroblastoma (NB). The
      sequestered p53 localizes to punctate cytoplasmic structures that represent large
      protein aggregates. One functional consequence of this blocked nuclear access is
      impairment of the p53-mediated G1 checkpoint after DNA damage. Here we show that
      cytoplasmic p53 from NB cells is incompetent for specific DNA binding, probably
      due to its sequestration. Importantly, the C-terminal domain of sequestered p53
      is masked, as indicated by the failure of a C-terminally directed antibody to
      detect p53 in these structures. To determine (i) which domain of p53 is involved
      in the aggregation and (ii) whether this phenotype is potentially reversible, we
      generated stable NB sublines that coexpress the soluble C-terminal mouse p53
      peptide DD1 (amino acids 302-390). A dramatic phenotypic reversion occurred in
      five of five lines. The presence of DD1 blocked the sequestration of wild-type
      p53 and relocated it to the nucleus, where it accumulated. The nuclear
      translocation is due to shuttling of wild-type p53 by heteroligomerization to
      DD1, as shown by coimmunoprecipitation. As expected, the nuclear heterocomplexes
      were functionally inactive, since DD1 is a dominant negative inhibitor of wild
      type p53. In summary, we show that nuclear access of p53 can be restored in NB
      cells.

PMID- 8986787
TI  - On the molecular basis and regulation of cellular capacitative calcium entry:
      roles for Trp proteins.
AB  - During the last 2 years, our laboratory has worked on the elucidation of the
      molecular basis of capacitative calcium entry (CCE) into cells. Specifically, we
      tested the hypothesis that CCE channels are formed of subunits encoded in genes
      related to the Drosophila trp gene. The first step in this pursuit was to search
      for mammalian trp genes. We found not one but six mammalian genes and cloned
      several of their cDNAs, some in their full length. As assayed in mammalian cells,
      overexpression of some mammalian Trps increases CCE, while expression of partial
      trp cDNAs in antisense orientation can interfere with endogenous CCE. These
      findings provided a firm connection between CCE and mammalian Trps. This article
      reviews the known forms of CCE and highlights unanswered questions in our
      understanding of intracellular Ca2+ homeostasis and the physiological roles of
      CCE.

PMID- 8986788
TI  - GAIP is membrane-anchored by palmitoylation and interacts with the activated (GTP
      bound) form of G alpha i subunits.
AB  - GAIP (G Alpha Interacting Protein) is a member of the recently described RGS
      (Regulators of G-protein Signaling) family that was isolated by interaction
      cloning with the heterotrimeric G-protein G alpha i3 and was recently shown to be
      a GTPase-activating protein (GAP). In AtT-20 cells stably expressing GAIP, we
      found that GAIP is membrane-anchored and faces the cytoplasm, because it was not
      released by sodium carbonate treatment but was digested by proteinase K. When Cos
      cells were transiently transfected with GAIP and metabolically labeled with
      [35S]methionine, two pools of GAIP--a soluble and a membrane-anchored pool--were
      found. Since the N terminus of GAIP contains a cysteine string motif and cysteine
      string proteins are heavily palmitoylated, we investigated the possibility that
      membrane-anchored GAIP might be palmitoylated. We found that after labeling with
      [3H]palmitic acid, the membrane-anchored pool but not the soluble pool was
      palmitoylated. In the yeast two-hybrid system, GAIP was found to interact
      specifically with members of the G alpha i subfamily, G alpha i1, G alpha i2, G
      alpha i3, G alpha z, and G alpha o, but not with members of other G alpha
      subfamilies, G alpha s, G alpha q, and G alpha 12/13. The C terminus of G alpha
      i3 is important for binding because a 10-aa C-terminal truncation and a point
      mutant of G alpha i3 showed significantly diminished interaction. GAIP interacted
      preferentially with the activated (GTP) form of G alpha i3, which is in keeping
      with its GAP activity. We conclude that GAIP is a membrane-anchored GAP with a
      cysteine string motif. This motif, present in cysteine string proteins found on
      synaptic vesicles, pancreatic zymogen granules, and chromaffin granules, suggests
      GAIP's possible involvement in membrane trafficking.

PMID- 8986789
TI  - DNA damage and p53-mediated cell cycle arrest: a reevaluation.
AB  - Most mammalian cells exhibit transient delays in the G1 and G2 phases of the cell
      cycle after treatment with radiation or radiomimetic compounds. p53 is required
      for the arrest in G1, which provides time for DNA repair. Recently, a role of p53
      in the G2/M transition has also been suggested. However, it has been reported
      that the presence of functional p53 does not always correlate with the induction
      of these checkpoints. To precisely assess the role of p53 in activating cell
      cycle checkpoints and in cell survival after radiation, we studied the response
      of two isogenic human fibrosarcoma cell lines differing in their p53 status (wild
      type or mutant). We found that when irradiated cells undergo a wild-type p53
      dependent G1 arrest, they do not subsequently arrest in G2. Moreover, wild-type
      p53 cells irradiated past the G1 checkpoint arrest in G2 but do not delay in the
      subsequent G1 phase. Furthermore, in these cell lines, which do not undergo
      radiation-induced apoptosis, the wild-type p53 cell line exhibited a greater
      radioresistance in terms of clonogenic survival. These results suggest that the
      two checkpoints may be interrelated, perhaps through a control system that
      determines, depending on the extent of the damage, whether the cell needs to
      arrest cell cycle progression at the subsequent checkpoint for further repair.
      p53 could be a crucial component of this control system.

PMID- 8986790
TI  - Cyclin E, a redundant cyclin in breast cancer.
AB  - Cyclin E is an important regulator of cell cycle progression that together with
      cyclin-dependent kinase (cdk) 2 is crucial for the G1/S transition during the
      mammalian cell cycle. Previously, we showed that severe overexpression of cyclin
      E protein in tumor cells and tissues results in the appearance of lower molecular
      weight isoforms of cyclin E, which together with cdk2 can form a kinase complex
      active throughout the cell cycle. In this study, we report that one of the
      substrates of this constitutively active cyclin E/cdk2 complex is retinoblastoma
      susceptibility gene product (pRb) in populations of breast cancer cells and
      tissues that also overexpress p16. In these tumor cells and tissues, we show that
      the expression of p16 and pRb is not mutually exclusive. Overexpression of p16 in
      these cells results in sequestering of cdk4 and cdk6, rendering cyclin D1/cdk
      complexes inactive. However, pRb appears to be phosphorylated throughout the cell
      cycle following an initial lag, revealing a time course similar to
      phosphorylation of glutathione S-transferase retinoblastoma by cyclin E
      immunoprecipitates prepared from these synchronized cells. Hence, cyclin E kinase
      complexes can function redundantly and replace the loss of cyclin D-dependent
      kinase complexes that functionally inactivate pRb. In addition, the
      constitutively overexpressed cyclin E is also the predominant cyclin found in
      p107/E2F complexes throughout the tumor, but not the normal, cell cycle. These
      observations suggest that overexpression of cyclin E in tumor cells, which also
      overexpress p16, can bypass the cyclin D/cdk4-cdk6/p16/pRb feedback loop,
      providing yet another mechanism by which tumors can gain a growth advantage.

PMID- 8986791
TI  - Microtubule reorganization is obligatory for growth cone turning.
AB  - To examine the role of microtubules in growth cone turning, we have compared the
      microtubule organization in growth cones advancing on uniform laminin substrates
      with their organization in growth cones turning at a laminin-tenascin border. The
      majority (82%) of growth cones on laminin had a symmetrical microtubule
      organization, in which the microtubules entering the growth cone splay out toward
      the periphery of the growth cone. Growth cones at tenascin borders had
      symmetrically arranged microtubules in only 34% of cases, whereas in the majority
      of cases the microtubules were displaced toward one-half of the growth cone,
      presumably stabilizing in the direction of the turn along the tenascin border.
      These results suggest that reorganization of microtubules could underlie growth
      cone turning. Further evidence for the involvement of microtubule rearrangement
      in growth cone turning was provided by experiments in which growth cones
      approached tenascin borders in the presence of nanomolar concentrations of the
      microtubule stabilizing compound, Taxol. Taxol altered the organization of
      microtubules in growth cones growing on laminin by restricting their distribution
      to the proximal regions of the growth cone and increasing their bundling. Taxol
      did not stop growth cone advance on laminin. When growing in the presence of
      Taxol, growth cones at tenascin borders were not able to turn and grow along the
      laminin-tenascin border, and consequently stopped at the border. Growth cones
      were arrested at borders for as long as Taxol was present (up to 6 h) without
      showing any signs of drug toxicity. These effects of Taxol were reversible.
      Together, these results suggest that microtubule reorganization in growth cones
      is a necessary event in growth cone turning.

PMID- 8986792
TI  - Homocysteine induces congenital defects of the heart and neural tube: effect of
      folic acid.
AB  - The biological basis or mechanism whereby folate supplementation protects against
      heart and neural tube defect is unknown. It has been hypothesized that the amino
      acid homocysteine may be the teratogenic agent, since serum homocysteine
      increases in folate depletion; however, this hypothesis has not been tested. In
      this study, avian embryos were treated directly with D,L-homocysteine or with L
      homocysteine thiolactone, and a dose response was established. Of embryos treated
      with 50 microliters of the teratogenic dose (200 mM D,L-homocysteine or 100 mM L
      homocysteine thiolactone) on incubation days 0, 1, and 2 and harvested at 53 h
      (stage 14), 27% showed neural tube defects. To determine the effect of the
      teratogenic dose on the process of heart septation, embryos were treated during
      incubation days 2, 3, and 4; then they were harvested at day 9 following the
      completion of septation. Of surviving embryos, 23% showed ventricular septal
      defects, and 11% showed neural tube defects. A high percentage of the day 9
      embryos also showed a ventral closure defect. The teratogenic dose was shown to
      raise serum homocysteine to over 150 nmol/ml, compared with a normal level of
      about 10 nmol/ml. Folate supplementation kept the rise in serum homocysteine to
      approximately 45 nmol/ml, and prevented the teratogenic effect. These results
      support the hypothesis that homocysteine per se causes dysmorphogenesis of the
      heart and neural tube, as well as of the ventral wall.

PMID- 8986793
TI  - Parathyroid hormone-related peptide (PTHrP) regulates fetal-placental calcium
      transport through a receptor distinct from the PTH/PTHrP receptor.
AB  - To determine the role of PTHrP in fetal calcium metabolism, blood calcium was
      measured in mice homozygous (HOM) for deletion of the PTHrP gene. On day 18.5 of
      gestation, ionized calcium and the maternal-fetal calcium gradient were
      significantly reduced in HOM PTHrP-ablated fetuses compared with that of their
      littermates. To assess the placental contribution to the effect of PTHrP, 45Ca
      and 51Cr-EDTA (as a blood diffusional marker) were administered by intracardiac
      injection to pregnant, heterozygous dams on day 17.5 of gestation. Five minutes
      after the injection, whole fetal 45Ca accumulation was significantly decreased in
      HOM PTHrP-ablated fetuses compared with that of their littermates. Next, two
      fetuses from each litter were injected in utero with fragments of PTHrP, PTH, or
      diluent 1 h before administering 45Ca and 51Cr to the dam. PTHrP-(1-86) and PTHrP
      (67-86) significantly increased relative 45Ca accumulation in HOM PTHrP-ablated
      fetuses, but PTHrP-(1-34), PTH-(1-84), and the diluent had no effect. Finally,
      similar studies were performed on fetal mice that lacked the PTH/PTHrP receptor
      gene. Ionized calcium was significantly reduced in HOM PTH/PTHrP receptor-ablated
      fetuses. However, 5 min after maternal injection of 45Ca and 51Cr, relative
      accumulation of 45Ca was significantly increased in these fetuses. It was
      concluded that PTHrP is an important regulator of fetal blood calcium and
      placental calcium transport. In addition, the bioactivity of PTHrP for placental
      calcium transport is specified by a mid-molecular region that does not use the
      PTH/PTHrP receptor.

PMID- 8986794
TI  - Multiple independent transpositions of mitochondrial DNA control region sequences
      to the nucleus.
AB  - Transpositions of mtDNA sequences to the nuclear genome have been documented in a
      wide variety of individual taxa, but little is known about their taxonomic
      frequency or patterns of variation. We provide evidence of nuclear sequences
      homologous to the mtDNA control region in seven species of diving ducks (tribe
      Aythyini). Phylogenetic analysis places each nuclear sequence as a close relative
      of the mtDNA haplotypes of the specie(s) in which it occurs, indicating that they
      derive from six independent transposition events, all occurring within the last
      approximately 1.5 million years. Relative-rate tests and comparison of
      intraspecific variation in nuclear and mtDNA sequences confirm the expectation of
      a greatly reduced rate of evolution in the nuclear copies. By representing mtDNA
      haplotypes from ancestral populations, nuclear insertions may be valuable in some
      phylogenetic analyses, but they also confound the accurate determination of mtDNA
      sequences. In particular, our data suggest that the presumably nonfunctional but
      more slowly evolving nuclear sequences often will not be identifiable by changes
      incompatible with function and may be preferentially amplified by PCR primers
      based on mtDNA sequences from related taxa.

PMID- 8986795
TI  - Independent evolution of the prochlorophyte and green plant chlorophyll a/b light
      harvesting proteins.
AB  - The prochlorophytes are oxygenic prokaryotes differing from other cyanobacteria
      by the presence of a light-harvesting system containing both chlorophylls (Chls)
      a and b and by the absence of phycobilins. We demonstrate here that the Chl a/b
      binding proteins from all three known prochlorophyte genera are closely related
      to IsiA, a cyanobacterial Chl a-binding protein induced by iron starvation, and
      to CP43, a constitutively expressed Chl a antenna protein of photosystem II. The
      prochlorophyte Chl a/b protein (pcb) genes do not belong to the extended gene
      family encoding eukaryotic Chl a/b and Chl a/c light-harvesting proteins.
      Although higher plants and prochlorophytes share common pigment complements,
      their light-harvesting systems have evolved independently.

PMID- 8986796
TI  - Evolutionary theory predicts late-life mortality plateaus.
AB  - Most demographic data indicate a roughly exponential increase in adult mortality
      with age, a phenomenon that has been explained in terms of a decline in the force
      of natural selection acting on age-specific mortality. Scattered demographic
      findings suggest the existence of a late-life mortality plateau in both humans
      and dipteran insects, seemingly at odds with both prior data and evolutionary
      theory. Extensions to the evolutionary theory of aging are developed which
      indicate that such late-life mortality plateaus are to be expected when enough
      late-life data are collected. This expanded theory predicts late-life mortality
      plateaus, with both antagonistic pleiotropy and mutation accumulation as driving
      population genetic mechanisms.

PMID- 8986797
TI  - Somatic and germ cell parasitism in a colonial ascidian: possible role for a
      highly polymorphic allorecognition system.
AB  - A colonial protochordate, Botryllus schlosseri, undergoes a natural
      transplantation reaction in the wild that results alternatively in colony fusion
      (chimera formation) or inflammatory rejection. A single, highly polymorphic
      histocompatibility locus (called Fu/HC) is responsible for rejection versus
      fusion. Gonads are seeded and gametogenesis can occur in colonies well after
      fusion, and involves circulating germ-line progenitors. Buss proposed that
      colonial organisms might develop self/non-self histocompatibility systems to
      limit the possibility of interindividual germ cell "parasitism" (GCP) to
      histocompatible kin [Buss, L. W. (1982) Proc. Natl. Acad. Sci. USA 79, 5337-5341
      and Buss, L. W. (1987) The Evolution of Individuality (Princeton Univ. Press,
      Princeton]. Here we demonstrate in laboratory and field experiments that both
      somatic cell and (more importantly) germ-line parasitism are a common occurrence
      in fused chimeras. These experiments support the tenet in Buss's hypothesis that
      germ cell and somatic cell parasitism can occur in fused chimeras and that a
      somatic appearance may mask the winner of a gametic war. They also provide an
      interesting challenge to develop formulas that describe the inheritance of
      competing germ lines rather than competing individuals. The fact that fused B.
      schlosseri have higher rates of GCP than unfused colonies additionally provides a
      rational explanation for the generation and maintenance of a high degree of Fu/HC
      polymorphism, largely limiting GCP to sibling offspring.

PMID- 8986798
TI  - Developmental signal transduction pathways uncovered by genetic suppressors.
AB  - We have found conditions for saturation mutagenesis by restriction enzyme
      mediated integration that result in plasmid tagging of disrupted genes. Using
      this method we selected for mutations in genes that act at checkpoints downstream
      of the intercellular signalling system that controls encapsulation in
      Dictyostelium discoideum. One of these genes, mkcA, is a member of the mitogen
      activating protein kinase cascade family while the other, regA is a novel
      bipartite gene homologous to response regulators in one part and to cyclic
      nucleotide phosphodiesterases in the other part. Disruption of either of these
      genes results in partial suppression of the block to spore formation resulting
      from the loss of the prestalk genes, tagB and tagC. The products of the tag genes
      have conserved domains of serine protease attached to ATP-driven transporters,
      suggesting that they process and export peptide signals. Together, these genes
      outline an intercellular communication system that coordinates organismal shape
      with cellular differentiation during development.

PMID- 8986800
TI  - Integration of Agrobacterium tumefaciens T-DNA in the Saccharomyces cerevisiae
      genome by illegitimate recombination.
AB  - Agrobacterium tumefaciens can transfer part of its Ti plasmid, the T-DNA, to
      plant cells where it integrates into the nuclear genome via illegitimate
      recombination. Integration of the T-DNA results in small deletions of the plant
      target DNA, and may lead to truncation of the T-DNA borders and the production of
      filler DNA. We showed previously that T-DNA can also be transferred from A.
      tumefaciens to Sac-charomyces cerevisiae and integrates into the yeast genome via
      homologous recombination. We show here that when the T-DNA lacks homology with
      the S. cerevisiae genome, it integrates at random positions via illegitimate
      recombination. From 11 lines the integrated T-DNA was cloned back to Escherichia
      coli along with yeast flanking sequences. The T-DNA borders and yeast DNA
      flanking the T-DNA were sequenced and characterized. It was found that T-DNA
      integration had resulted in target DNA deletions and sometimes T-DNA truncations
      or filler DNA formation. Therefore, the molecular mechanism of illegitimate
      recombination by which T-DNA integrates in higher and lower eukaryotes seems
      conserved.

PMID- 8986799
TI  - Transduction of nondividing cells using pseudotyped defective high-titer HIV type
      1 particles.
AB  - The use of Moloney murine leukemia virus (Mo-MLV)-based vectors to deliver
      therapeutic genes into target cells is limited by their inability to transduce
      nondividing cells. To test the capacity of HIV-based vectors to deliver genes
      into nondividing cells, we have generated replication-defective HIV type 1 (HIV
      1) reporter vectors carrying neomycin phosphotransferase or mouse heat stable
      antigen, replacing the HIV-1 sequences encoding gp160. These vectors also harbor
      inactive vpr, vpu, and nef coding regions. Pseudotyped HIV-1 particles carrying
      either the ecotropic or the amphotropic Mo-MLV envelope proteins or the vesicular
      stomatitis virus G protein were released after single or double transfections of
      either human 293T or monkey COS-7 cells with titers of up to 10(7) colony-forming
      units per milliliter. A simple ultrafiltration procedure resulted in an
      additional 10- to 20-fold concentration of the pseudotyped particles. These
      vectors along with Mo-MLV-based vectors were used to transduce primary human skin
      fibroblasts and human peripheral blood CD34+ cells. The HIV-1 vector system was
      significantly more efficient than its Mo-MLV-based counterpart in transducing
      human skin fibroblasts arrested at the G0/G1 stage of the cell cycle by density
      dependent inhibition of growth. Human CD34+ cells were transduced efficiently
      using HIV-1 pseudotype particles without prior stimulation with cytokines.

PMID- 8986801
TI  - The Malthusian parameter of ascents: what prevents the exponential increase of
      one's ancestors?
AB  - The reason that the indefinite exponential increase in the number of one's
      ancestors does not take place is found in the law of sibling interference, which
      can be expressed by the following simple equation: [equation: see text] where Nn
      is the number of ancestors in the nth generation, ASZ is the average sibling size
      of these ancestors, and Nn + 1 is the number of ancestors in the next older
      generation (n + 1). Accordingly, the exponential increase in the number of one's
      ancestors is an initial anomaly that occurs while ASZ remains at 1. Once ASZ
      begins to exceed 1, the rate of increase in the number of ancestors is
      progressively curtailed, falling further and further behind the exponential
      increase rate. Eventually, ASZ reaches 2, and at that point, the number of
      ancestors stops increasing for two generations. These two generations, named AN
      SA and AN SA + 1, are the most critical in the ancestry, for one's ancestors at
      that point come to represent all the progeny-produced adults of the entire
      ancestral population. Thereafter, the fate of one's ancestors becomes the fate of
      the entire population. If the population to which one belongs is a successful,
      slowly expanding one, the number of ancestors would slowly decline as you move
      toward the remote past. This is because ABZ would exceed 2. Only when ABZ is less
      than 2 would the number of ancestors increase beyond the AN SA and AN SA + 1
      generations. Since the above is an indication of a failing population on the way
      to extinction, there had to be the previous AN SA involving a far greater number
      of individuals for such a population. Simulations indicated that for a member of
      a continuously successful population, the AN SA ancestors might have numbered as
      many as 5.2 million, the AN SA generation being the 28th generation in the past.
      However, because of the law of increasingly irrelevant remote ancestors, only a
      very small fraction of the AN SA ancestors would have left genetic traces in the
      genome of each descendant of today.

PMID- 8986803
TI  - Mutation rate varies among alleles at a microsatellite locus: phylogenetic
      evidence.
AB  - The understanding of the mutational mechanism that generates high levels of
      variation at microsatellite loci lags far behind the application of these genetic
      markers. A phylogenetic approach was developed to study the pattern and rate of
      mutations at a dinucleotide microsatellite locus tightly linked to HLA-DQB1
      (DQCAR). A random Japanese population (n = 129) and a collection of multiethnic
      samples (n = 941) were typed at the DQB1 and DQCAR loci. The phylogeny of DQB1
      alleles was then reconstructed and DQCAR alleles were superimposed onto the
      phylogeny. This approach allowed us to group DQCAR alleles that share a common
      ancestor. The results indicated that the DQCAR mutation rate varies drastically
      among alleles within this single microsatellite locus. Some DQCAR alleles never
      mutated during a long period of evolutionary time. Sequencing of representative
      DQCAR alleles showed that these alleles lost their ability to mutate because of
      nucleotide substitutions that shorten the length of uninterrupted CA repeat
      arrays; in contrast, all mutating alleles had relatively longer perfect CA repeat
      sequences.

PMID- 8986802
TI  - Identification of genes induced by factor deprivation in hematopoietic cells
      undergoing apoptosis using gene-trap mutagenesis and site-specific recombination.
AB  - A strategy employing gene-trap mutagenesis and site-specific recombination
      (Cre/loxP) has been developed to isolate genes that are transcriptionally
      activated during programmed cell death. Interleukin-3 (IL-3)-dependent
      hematopoietic precursor cells (FDCP1) expressing a reporter plasmid that codes
      for herpes simplex virus-thymidine kinase, neomycin phosphotransferase, and
      murine IL-3 were transduced with a retroviral gene-trap vector carrying coding
      sequences for Cre-recombinase (Cre) in the U3 region. Activation of Cre
      expression from integrations into active genes resulted in a permanent switching
      between the selectable marker genes that converted the FDCP1 cells to factor
      independence. Selection for autonomous growth yielded recombinants in which Cre
      sequences in the U3 region were expressed from upstream cellular promoters.
      Because the expression of the marker genes is independent of the trapped cellular
      promoter, genes could be identified that were transiently induced by IL-3
      withdrawal.

PMID- 8986804
TI  - Induction of HSP70 and polyubiquitin expression associated with plant virus
      replication.
AB  - By examining the front of virus invasion in immature pea embryos infected with
      pea seed-borne mosaic virus (PSbMV), the selective control of different host
      genes has been observed. From our observations, the early responses to PSbMV
      replication can be grouped into three classes, inhibited host gene expression,
      induced host gene expression, and no effect on a normal host function. The
      expression of two heat-inducible genes encoding HSP70 and polyubiquitin was
      induced coordinately with the onset of virus replication and the down-regulation
      of two other genes encoding lipoxygenase and heat shock cognate protein. The down
      regulation was part of a general suppression of host gene expression that may be
      achieved through the degradation of host transcripts. We discuss the
      possibilities of whether the induction of HSP70 and polyubiquitin genes
      represents a requirement for the respective protein products by the virus or is
      merely a consequence of the depletion of other host transcripts. The former is
      feasible, as the induction of both genes does result in increased HSP70 and
      ubiquitin accumulation. This also indicates that, in contrast to some animal
      virus infections, there is not a general inhibition of translation of host mRNAs
      following PSbMV infection. This selective control of host gene expression was
      observed in all cell types of the embryo and identifies mechanisms of cellular
      disruption that could act as triggers for symptom expression.

PMID- 8986805
TI  - Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in
      t(X;1)(p11;q21)-positive papillary renal cell carcinomas.
AB  - The (X;1)(p11;q21) translocation is a recurrent chromosomal abnormality in a
      subset of human papillary renal cell carcinomas, and is sometimes the sole
      cytogenetic abnormality present. Via positional cloning, we were able to identify
      the genes involved. The translocation results in a fusion of the transcription
      factor TFE3 gene on the X chromosome to a novel gene, designated PRCC, on
      chromosome 1. Through this fusion, reciprocal translocation products are formed,
      which are both expressed in papillary renal cell carcinomas. PRCC is ubiquitously
      expressed in normal adult and fetal tissues and encodes a putative protein of 491
      aa with a relatively high content of prolines. No relevant homologies with known
      sequences at either the DNA or the protein level were found.

PMID- 8986806
TI  - A novel member of the RING finger family, KRIP-1, associates with the KRAB-A
      transcriptional repressor domain of zinc finger proteins.
AB  - The Kruppel-associated box A (KRAB-A) domain is an evolutionarily conserved
      transcriptional repressor domain present in approximately one-third of zinc
      finger proteins of the Cys2-His2 type. Using the yeast two-hybrid system, we
      report the isolation of a cDNA encoding a novel murine protein, KRAB-A
      interacting protein 1 (KRIP-1) that physically interacts with the KRAB-A region.
      KRIP-1 is a member of the RBCC subfamily of the RING finger, or Cys3HisCys4,
      family of zinc binding proteins whose other members are known to play important
      roles in differentiation, oncogenesis, and signal transduction. The KRIP-1
      protein has high homology to TIF1, a putative modulator of ligand-dependent
      activation function of nuclear receptors. A 3.5-kb mRNA for KRIP-1 is
      ubiquitously expressed among all adult mouse tissues studied. When a GAL4-KRIP-1
      fusion protein is expressed in COS cells with a chloramphenicol acetyltransferase
      reporter construct with five GAL4 binding sites, there is dose-dependent
      repression of transcription. Thus, KRIP-1 interacts with the KRAB-A region of
      C2H2 zinc finger proteins and may mediate or modulate KRAB-A transcriptional
      repressor activity.

PMID- 8986807
TI  - The common nodABC genes of Rhizobium meliloti are host-range determinants.
AB  - Symbiotic bacteria of the genus Rhizobium synthesize lipo-chitooligosaccharides,
      called Nod factors (NFs), which act as morphogenic signal molecules on legume
      hosts. The common nodABC genes, present in all Rhizobium species, are required
      for the synthesis of the core structure of NFs. NodC is an N
      acetylglucosaminyltransferase, and NodB is a chitooligosaccharide deacetylase;
      NodA is involved in N-acylation of the aminosugar backbone. Specific nod genes
      are involved in diverse NF substitutions that confer plant specificity. We
      transferred to R. tropici, a broad host-range tropical symbiont, the ability to
      nodulate alfalfa, by introducing nod genes of R. meliloti. In addition to the
      specific nodL and nodFE genes, the common nodABC genes of R. meliloti were
      required for infection and nodulation of alfalfa. Purified NFs of the R. tropici
      hybrid strain, which contained chitin tetramers and were partly N-acylated with
      unsaturated C16 fatty acids, were able to elicit nodule formation on alfalfa.
      Inactivation of the R. meliloti nodABC genes suppressed the ability of the NFs to
      nodulate alfalfa. Studies of NFs from nodA, nodB, nodC, and nodI mutants indicate
      that (i) NodA of R. meliloti, in contrast to NodA of R. tropici, is able to
      transfer unsaturated C16 fatty acids onto the chitin backbone and (ii) NodC of R.
      meliloti specifies the synthesis of chitin tetramers. These results show that
      allelic variation of the common nodABC genes is a genetic mechanism that plays an
      important role in signaling variation and in the control of host range.

PMID- 8986808
TI  - HMG I(Y) interferes with the DNA binding of NF-AT factors and the induction of
      the interleukin 4 promoter in T cells.
AB  - HMG I(Y) proteins bind to double-stranded A + T oligonucleotides longer than
      three base pairs. Such motifs form part of numerous NF-AT-binding sites of
      lymphokine promoters, including the interleukin 4 (IL-4) promoter. NF-AT factors
      share short homologous peptide sequences in their DNA-binding domain with NF
      kappa B factors and bind to certain NF-kappa B sites. It has been shown that HMG
      I(Y) proteins enhance NF-kappa B binding to the interferon beta promoter and
      virus-mediated interferon beta promoter induction. We show that HMG I(Y) proteins
      exert an opposite effect on the DNA binding of NF-AT factors and the induction of
      the IL-4 promoter in T lymphocytes. Introduction of mutations into a high
      affinity HMG I(Y)-binding site of the IL-4 promoter, which decreased HMG I(Y)
      binding to a NF-AT-binding sequence, the Pu-bB (or P) site, distinctly increased
      the induction of the IL-4 promoter in Jurkat T leukemia cells. High
      concentrations of HMG I(Y) proteins are able to displace NF-ATp from its binding
      to the Pu-bB site. High HMG I(Y) concentrations are typical for Jurkat cells and
      peripheral blood T lymphocytes, whereas E14 T lymphoma cells and certain T helper
      type 2 cell clones contain relatively low HMG I(Y) concentrations. Our results
      indicate that HMG I(Y) proteins do not cooperate, but instead compete with NF-AT
      factors for the binding to DNA even though NF-AT factors share some DNA-binding
      to DNA even though NF-AT factors share some DNA-binding properties with NF-kB
      factors. This competition between HMG I(Y) and NF-AT proteins for DNA binding
      might be due to common contacts with minor groove nucleotides of DNA and may be
      one mechanism contributing to the selective IL-4 expression in certain T
      lymphocyte populations, such as T helper type 2 cells.

PMID- 8986809
TI  - Complementary mutations in an antigenic peptide allow for crossreactivity of
      autoreactive T-cell clones.
AB  - T cells recognize antigen by formation of a trimolecular complex in which the T
      cell receptor (TCR) recognizes a specific peptide antigen within the groove of a
      major histocompatibility complex (MHC) molecule. It has generally been assumed
      that T-cell recognition of two distinct MHC-antigen complexes is due to
      similarities in the three-dimensional structure of the complexes. Here we report
      results of experiments examining the crossreactivity of TCRs recognizing the
      myelin basic protein peptide MBPp85-99 and several of its analogs in the context
      of MHC. We demonstrate that single conservative amino acid substitutions of the
      antigenic peptide at the predominant TCR contact residues at positions 91 and 93
      totally abrogate reactivity of specific T-cell clones. Yet, when a conservative
      substitution is made at position 91 concomitant with a substitution at position
      93, the T-cell clones regain reactivity equivalent with that of the original
      stimulating peptide. Thus, the exact nature of the amino acid side chains
      engaging one TCR functional pocket may change the apparent selectivity of the
      other predominant TCR functional pocket, thus suggesting a remarkable degree of
      receptor plasticity. This ability of the TCR-MHC-peptide complex to undergo
      conformational changes provides a conceptual framework for reconciling the
      apparent paradox of the extreme selectivity of the TCR and its remarkable
      crossreactivity with different MHC-peptide complexes.

PMID- 8986810
TI  - Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection.
AB  - To understand the role of the immune system in limiting HIV type 1 replication,
      it is critical to know to what extent the rapid turnover of productively infected
      cells is caused by viral cytopathicity or by immune-mediated lysis. We show that
      uncultured peripheral blood mononuclear cells of many patients contain cytotoxic
      T lymphocytes (CTL) that lyse target cells-at plausible peripheral blood
      mononuclear cell-to-target ratios-with half-lives of less than 1 day. In 23
      patients with CD4 counts ranging from 10 to 900 per microliter, the average rate
      of CTL-mediated lysis corresponds to a target cell half-life of 0.7 day. We
      develop mathematical models to calculate the turnover rate of infected cells
      subjected to immune-mediated lysis and viral cytopathicity and to estimate the
      fraction of cells that are killed by CTL as opposed to virus. The models provide
      new interpretations of drug treatment dynamics and explain why the observed rate
      of virus decline is roughly constant for different patients. We conclude that in
      HIV type 1 infection, CTL-mediated lysis can reduce virus load by limiting virus
      production, with small effects on the half-life of infected cells.

PMID- 8986811
TI  - Characterization of avian T-cell receptor gamma genes.
AB  - In birds and mammals T cells develop along two discrete pathways characterized by
      expression of either the alpha beta or the gamma delta T-cell antigen receptors
      (TCRs). To gain further insight into the evolutionary significance of the gamma
      delta T-cell lineage, the present studies sought to define the chicken TCR gamma
      locus. A splenic cDNA library was screened with two polymerase chain reaction
      products obtained from genomic DNA using primers for highly conserved regions of
      TCR and immunoglobulin genes. This strategy yielded cDNA clones with
      characteristics of mammalian TCR gamma chains, including canonical residues
      considered important for proper folding and stability. Northern blot analysis
      with the TCR gamma cDNA probe revealed 1.9-kb transcripts in the thymus, spleen,
      and a gamma delta T-cell line, but not in B or alpha beta T-cell lines. Three
      multimember V gamma subfamilies, three J gamma gene segments, and a single
      constant region C gamma gene were identified in the avian TCR gamma locus.
      Members of each of the three V gamma subfamilies were found to undergo
      rearrangement in parallel during the first wave of thymocyte development. TCR
      gamma repertoire diversification was initiated on embryonic day 10 by an
      apparently random pattern of V-J gamma recombination, nuclease activity, and P
      and N-nucleotide additions to generate a diverse repertoire of avian TCR gamma
      genes early in ontogeny.

PMID- 8986812
TI  - Identification of a novel p53 functional domain that is necessary for efficient
      growth suppression.
AB  - Activation of the p53 tumor suppressor protein has been demonstrated to block
      cell growth by inducing either a transient cell cycle arrest or programmed cell
      death (apoptosis). Although evidence exists linking p53's function as an
      activator of transcription to its ability to effect cell cycle arrest, the role
      of this activity in the induction of apoptosis remains unclear. To gain insight
      into the molecular mechanisms underlying p53-mediated antiproliferative pathways,
      a study was initiated to explore the functions of a putative p53 signaling
      domain. This region of the human p53 protein is localized between amino acids 61
      and 94 (out of 393) and is noteworthy in that it contains five repeats of the
      sequence PXXP (where P represents proline and X any amino acid). This motif has
      been shown to play a role in signal transduction via its SH3 domain binding
      activity. A p53 cDNA deletion mutant (delta pro AE), which lacks this entire
      proline-rich domain (deleted for amino acids 62-91), was created and
      characterized for a variety of p53 functions. The entire domain has been shown to
      be completely dispensable for transcriptional activation. On the other hand, this
      deletion of the p53 proline-rich domain impairs p53's ability to suppress tumor
      cell growth in culture. Amino acid substitution mutations at residues 22 and 23
      of p53 (eliminates transcriptional activity) also impair p53-mediated inhibition
      of cell growth in culture. Unlike wild-type p53, the delta proAE mutant cDNA can
      be stably expressed in tumor derived cell lines with few immediate detrimental
      effects. These cells express physiologic levels of p53 protein that are induced
      normally in response to DNA damage, indicating that removal of the proline-rich
      domain does not disrupt p53's upstream regulation by DNA damage. These data
      indicate that, in addition to the transcriptional activation domain, the p53
      proline-rich domain plays a critical role in the transmission of
      antiproliferative signals down-stream of the p53 protein and may link p53 to a
      direct signal transduction pathway.

PMID- 8986813
TI  - CD8+ T-cell-derived soluble factor(s), but not beta-chemokines RANTES, MIP-1
      alpha, and MIP-1 beta, suppress HIV-1 replication in monocyte/macrophages.
AB  - It has been demonstrated that CD8+ T cells produce a soluble factor(s) that
      suppresses human immuno-deficiency virus (HIV) replication in CD4+ T cells. The
      role of soluble factors in the suppression of HIV replication in
      monocyte/macrophages (M/M) has not been fully delineated. To investigate whether
      a CD8+ T-cell-derived soluble factor(s) can also suppress HIV infection in the
      M/M system, primary macrophages were infected with the macrophage tropic HIV-1
      strain Ba-L. CD8+ T-cell-depleted peripheral blood mononuclear cells were also
      infected with HIV-1 IIIB or Ba-L. HIV expression from the chronically infected
      macrophage cell line U1 was also determined in the presence of CD8+ T-cell
      supernatants or beta-chemokines. We demonstrate that: (i) CD8+ T-cell
      supernatants did, but beta-chemokines did not, suppress HIV replication in the
      M/M system; (ii) antibodies to regulated on activation normal T-cell expressed
      and Secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1 alpha) and
      MIP-1 beta did not, whereas antibodies to interleukin 10, interleukin 13,
      interferon alpha, or interferon gamma modestly reduced anti-HIV activity of the
      CD8+ T-cell supernatants; and (iii) the CD8+ T-cell supernatants did, but beta
      chemokines did not, suppress HIV-1 IIIB replication in peripheral blood
      mononuclear cells as well as HIV expression in U1 cells. These results suggest
      that HIV-suppressor activity of CD8+ T cells is a multifactorial phenomenon, and
      that RANTES, MIP-1 alpha, and MIP-1 beta do not account for the entire scope of
      CD8+ T-cell-derived HIV-suppressor factors.

PMID- 8986814
TI  - Results of MDR-1 vector modification trial indicate that granulocyte/macrophage
      colony-forming unit cells do not contribute to posttransplant hematopoietic
      recovery following intensive systemic therapy.
AB  - To formally test the hypothesis that the granulocyte/macrophage colony-forming
      unit (GM-CFU) cells can contribute to early hematopoietic reconstitution
      immediately after transplant, the frequency of genetically modified GM-CFU after
      retroviral vector transduction was measured by a quantitative in situ polymerase
      chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1)
      vector, and by a quantitative GM-CFU methylcellulose plating assay. The results
      of this analysis showed no difference between the transduction frequency in the
      products of two different transduction protocols: "suspension transduction" and
      "stromal growth factor transduction." However, when an analysis of the frequency
      of cells positive for the retroviral MDR-1 vector posttransplantation was carried
      out, 0 of 10 patients transplanted with cells transduced by the suspension method
      were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients
      transplanted with the cells transduced by the stromal growth factor method were
      positive for the MDR-1 vector transcription unit by in situ or in solution PCR
      assay (a difference that is significant at the P = 0.0065 level by the Fisher
      exact test). These data suggest that only very small subsets of the GM-CFU
      fraction of myeloid cells, if any, contribute to the repopulation of the
      hematopoietic tissues that occurs following intensive systemic therapy and
      transplantation of autologous hematopoietic cells.

PMID- 8986815
TI  - A novel modifier gene for plasma von Willebrand factor level maps to distal mouse
      chromosome 11.
AB  - Type 1 von Willebrand disease (VWD), characterized by reduced levels of plasma
      von Willebrand factor (VWF), is the most common inherited bleeding disorder in
      humans. Penetrance of VWD is incomplete, and expression of the bleeding phenotype
      is highly variable. In addition, plasma VWF levels vary widely among normal
      individuals. To identify genes that influence VWF level, we analyzed a genetic
      cross between RIIIS/J and CASA/Rk, two strains of mice that exhibit a 20-fold
      difference in plasma VWF level. DNA samples from F2 progeny demonstrating either
      extremely high or extremely low plasma VWF levels were pooled and genotyped for
      41 markers spanning the autosomal genome. A novel locus accounting for 63% of the
      total variance in VWF level was mapped to distal mouse chromosome 11, which is
      distinct from the murine Vwf locus on chromosome 6. We designated this locus Mvwf
      for "modifier of VWF." Additional genotyping of as many as 2407 meioses
      established a high resolution genetic map with gene order Cola1-Itg3a-Ngfr
      Mvwf/Gip-Hoxb9-Hoxb1++ +-Cbx'rs2-Cox5a-Gfap. The Mvwf candidate interval between
      Ngfr and Hoxb9 is approximately 0.5 centimorgan (cM). These results demonstrate
      that a single dominant gene accounts for the low VWF phenotype of RIIIS/J mice in
      crosses with several other strains. The pattern of inheritance suggests a gain-of
      function mutation in a unique component of VWF biosynthesis or processing.
      Characterization of the human homologue for Mvwf may have relevance for a subset
      of type 1 VWD cases and may define an important genetic factor modifying
      penetrance and expression of mutations at the VWF locus.

PMID- 8986816
TI  - Definition of HLA-DQ as a transplantation antigen.
AB  - Recent studies have demonstrated the importance of recipient HLA-DRB1 allele
      disparity in the development of acute graft-versus-host disease (GVHD) after
      unrelated donor marrow transplantation. The role of HLA-DQB1 allele disparity in
      this clinical setting is unknown. To elucidate the biological importance of HLA
      DQB1, we conducted a retrospective analysis of 449 HLA-A, -B, and -DR
      serologically matched unrelated donor transplants. Molecular typing of HLA-DRB1
      and HLA-DQB1 alleles revealed 335 DRB1 and DQB1 matched pairs; 41 DRB1 matched
      and DQB1 mismatched pairs; 48 DRB1 mismatched and DQB1 matched pairs; and 25 DRB1
      and DQB1 mismatched pairs. The conditional probabilities of grades III-IV acute
      GVHD were 0.42, 0.61, 0.55, and 0.71, respectively. The relative risk of acute
      GVHD associated with a single locus HLA-DQB1 mismatch was 1.8 (1.1, 2.7; P =
      0.01), and the risk associated with any HLA-DQB1 and/or HLA-DRB1 mismatch was 1.6
      (1.2, 2.2; P = 0.003). These results provide evidence that HLA-DQ is a transplant
      antigen and suggest that evaluation of both HLA-DQB1 and HLA-DRB1 is necessary in
      selecting potential donors.

PMID- 8986817
TI  - Effect of age on in vivo rates of mitochondrial protein synthesis in human
      skeletal muscle.
AB  - A progressive decline in muscle performance in the rapidly expanding aging
      population is causing a dramatic increase in disability and health care costs. A
      decrease in muscle endurance capacity due to mitochondrial decay likely
      contributes to this decline in muscle performance. We developed a novel stable
      isotope technique to measure in vivo rates of mitochondrial protein synthesis in
      human skeletal muscle using needle biopsy samples and applied this technique to
      elucidate a potential mechanism for the age-related decline in the mitochondrial
      content and function of skeletal muscle. The fractional rate of muscle
      mitochondrial protein synthesis in young humans (24 +/- 1 year) was 0.081 +/-
      0.004%.h-1, and this rate declined to 0.047 +/- 0.005%.h-1 by middle age (54 +/-
      1 year; P < 0.01). No further decline in the rate of mitochondrial protein
      synthesis (0.051 +/- 0.004%.h-1) occurred with advancing age (73 +/- 2 years).
      The mitochondrial synthesis rate was about 95% higher than that of mixed protein
      in the young, whereas it was approximately 35% higher in the middle-aged and
      elderly subjects. In addition, decreasing activities of mitochondrial enzymes
      were observed in muscle homogenates (cytochrome c oxidase and citrate synthase)
      and in isolated mitochondria (citrate synthase) with increasing age, indicating
      declines in muscle oxidative capacity and mitochondrial function, respectively.
      The decrease in the rates of mitochondrial protein synthesis is likely to be
      responsible for this decline in muscle oxidative capacity and mitochondrial
      function. These changes in muscle mitochondrial protein metabolism may contribute
      to the age-related decline in aerobic capacity and muscle performance.

PMID- 8986818
TI  - Cell surface expression of the epithelial Na channel and a mutant causing Liddle
      syndrome: a quantitative approach.
AB  - The epithelial amiloride-sensitive sodium channel (ENaC) controls transepithelial
      Na+ movement in Na(+)-transporting epithelia and is associated with Liddle
      syndrome, an autosomal dominant form of salt-sensitive hypertension. Detailed
      analysis of ENaC channel properties and the functional consequences of mutations
      causing Liddle syndrome has been, so far, limited by lack of a method allowing
      specific and quantitative detection of cell-surface-expressed ENaC. We have
      developed a quantitative assay based on the binding of 125I-labeled M2 anti-FLAG
      monoclonal antibody (M2Ab*) directed against a FLAG reporter epitope introduced
      in the extracellular loop of each of the alpha, beta, and gamma ENaC subunits.
      Insertion of the FLAG epitope into ENaC sequences did not change its functional
      and pharmacological properties. The binding specificity and affinity (Kd = 3 nM)
      allowed us to correlate in individual Xenopus oocytes the macroscopic amiloride
      sensitive sodium current (INa) with the number of ENaC wild-type and mutant
      subunits expressed at the cell surface. These experiments demonstrate that: (i)
      only heteromultimeric channels made of alpha, beta, and gamma ENaC subunits are
      maximally and efficiently expressed at the cell surface; (ii) the overall ENaC
      open probability is one order of magnitude lower than previously observed in
      single-channel recordings; (iii) the mutation causing Liddle syndrome (beta
      R564stop) enhances channel activity by two mechanisms, i.e., by increasing ENaC
      cell surface expression and by changing channel open probability. This
      quantitative approach provides new insights on the molecular mechanisms
      underlying one form of salt-sensitive hypertension.

PMID- 8986819
TI  - L-selectin activates the Ras pathway via the tyrosine kinase p56lck.
AB  - Selectins mediate rolling, the initial step of leukocyte adhesion to endothelial
      cells [Springer, T. A. (1995) Annu. Rev. Physiol. 57, 827-872 and Butcher, E. C.
      (1991) Cell 67, 1033-1036]. In this study we show that L-selectin triggering of
      Jurkat cells using different antibodies or glycomimetics resulted in activation
      of the src-tyrosine kinase p56lck; tyrosine phosphorylation of intracellular
      proteins, in particular mitogen-activating protein kinase and L-selectin; and
      association of Grb2/Sos with L-selectin. This association correlated with an
      activation of p21Ras, mitogen-activating protein kinase, Rac2, and a transient
      increase of 2-O synthesis. Stimulation of the Ras pathway by L-selectin requires
      functional p56lck, since p56lck-deficient Jurkat cells (JCaM1.6) do not show
      tyrosine phosphorylation, association of L-selectin with Grb2/Sos, and activation
      of Ras upon L-selectin triggering. Transfection of JCaM1.6 cells with p56lck
      reconstitutes the observed signaling events. Genetic inhibition of Ras or Rac2
      prevented Rac2 stimulation and 2-O synthesis, respectively. The specificity and
      the physiological significance of the observed signaling cascade is indicated by
      stimulation of L-selectin-transfected P815, L-selectin-positive CEM or peripheral
      blood lymphocytes resulting in the same activation events as in Jurkat cells. Our
      results point to a signaling cascade from L-selectin via p56lck, Grb2/Sos, Ras,
      and Rac2 to 2-O.

PMID- 8986820
TI  - Sensitivity to inhibition by beta-chemokines correlates with biological
      phenotypes of primary HIV-1 isolates.
AB  - Primary HIV-1 isolates were evaluated for their sensitivity to inhibition by beta
      chemokines RANTES (regulated upon activation, normal T-cell expressed and
      secreted), macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta.
      Virus isolates of both nonsyncytium-inducing (NSI) and syncytium-inducing (SI)
      biological phenotypes recovered from patients at various stages of HIV-1
      infection were assessed, and the results indicated that only the isolates with
      the NSI phenotype were substantially inhibited by the beta-chemokines. More
      important to note, these data demonstrate that resistance to inhibition by beta
      chemokines RANTES, MIP-1 alpha, and MIP-1 beta is not restricted to T cell line
      adapted SI isolates but is also a consistent property among primary SI isolates.
      Analysis of isolates obtained sequentially from infected individuals in whom
      viruses shifted from NSI to SI phenotype during clinical progression exhibited a
      parallel loss of sensitivity to beta-chemokines. Loss of virus sensitivity to
      inhibition by beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta was furthermore
      associated with changes in the third variable (V3) region amino acid residues
      previously described to correlate with a shift of virus phenotype from NSI to SI.
      Of interest, an intermediate V3 genotype correlated with a partial inhibition by
      the beta-chemokines. In addition, we also identified viruses sensitive to RANTES,
      MIP-1 alpha, and MIP-1 beta of NSI phenotype that were isolated from individuals
      with AIDS manifestations, indicating that loss of sensitivity to beta-chemokine
      inhibition and shift in viral phenotype are not necessarily prerequisites for the
      pathogenesis of HIV-1 infection.

PMID- 8986821
TI  - Immune response in human melanoma after transfer of an allogeneic class I major
      histocompatibility complex gene with DNA-liposome complexes.
AB  - Analysis of the antitumor immune response after gene transfer of a foreign major
      histocompatibility complex class I protein, HLA-B7, was performed. Ten HLA-B7
      negative patients with stage IV melanoma were treated in an effort to stimulate
      local tumor immunity. Plasmid DNA was detected within treated tumor nodules, and
      RNA encoding recombinant HLA-B7 or HLA-B7 protein was demonstrated in 9 of 10
      patients. T cell migration into treated lesions was observed and tumor
      infiltrating lymphocyte reactivity was enhanced in six of seven and two of two
      patients analyzed, respectively. In contrast, the frequency of cytotoxic T
      lymphocyte against autologous tumor in circulating peripheral blood lymphocytes
      was not altered significantly, suggesting that peripheral blood lymphocyte
      reactivity is not indicative of local tumor responsiveness. Local inhibition of
      tumor growth was detected after gene transfer in two patients, one of whom showed
      a partial remission. This patient subsequently received treatment with tumor
      infiltrating lymphocytes derived from gene-modified tumor, with a complete
      regression of residual disease. Thus, gene transfer with DNA-liposome complexes
      encoding an allogeneic major histocompatibility complex protein stimulated local
      antitumor immune responses that facilitated the generation of effector cells for
      immunotherapy of cancer.

PMID- 8986822
TI  - Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum
      against the hypervariable region 1 of the envelope 2 protein.
AB  - The identification of the neutralization domains of hepatitis C virus (HCV) is
      essential for the development of an effective vaccine. Here, we show that the
      hypervariable region 1 (HVR1) of the envelope 2 (E2) protein is a critical
      neutralization domain of HCV. Neutralization of HCV in vitro was attempted with a
      rabbit hyperimmune serum raised against a homologous synthetic peptide derived
      from the HVR1 of the E2 protein, and the residual infectivity was evaluated by
      inoculation of HCV-seronegative chimpanzees. The source of HCV was plasma
      obtained from a patient (H) during the acute phase of posttransfusion non-A, non
      B hepatitis, which had been titered for infectivity in chimpanzees. The anti-HVR1
      antiserum induced protection against homologous HCV infection in chimpanzees, but
      not against the emergence of neutralization escape mutants that were found to be
      already present in the complex viral quasispecies of the inoculum. The finding
      that HVR1 can elicit protective immunity opens new perspectives for the
      development of effective preventive strategies. However, the identification of
      the most variable region of HCV as a critical neutralization domain poses a major
      challenge for the development of a broadly reactive vaccine against HCV.

PMID- 8986823
TI  - Rescue of a segmented negative-strand RNA virus entirely from cloned
      complementary DNAs.
AB  - We provide the first report, to our knowledge, of a helper-independent system for
      rescuing a segmented, negative-strand RNA genome virus entirely from cloned
      cDNAs. Plasmids were constructed containing full-length cDNA copies of the three
      Bunyamwera bunyavirus RNA genome segments flanked by bacteriophage T7 promoter
      and hepatitis delta virus ribozyme sequences. When cells expressing both
      bacteriophage T7 RNA polymerase and recombinant Bunyamwera bunyavirus proteins
      were transfected with these plasmids, full-length antigenome RNAs were
      transcribed intracellularly, and these in turn were replicated and packaged into
      infectious bunyavirus particles. The resulting progeny virus contained specific
      genetic tags characteristic of the parental cDNA clones. Reassortant viruses
      containing two genome segments of Bunyamwera bunyavirus and one segment of
      Maguari bunyavirus were also produced following transfection of appropriate
      plasmids. This accomplishment will allow the full application of recombinant DNA
      technology to manipulate the bunyavirus genome.

PMID- 8986824
TI  - Muramic lactam in peptidoglycan of Bacillus subtilis spores is required for spore
      outgrowth but not for spore dehydration or heat resistance.
AB  - Bacterial endospores derive much of their longevity and resistance properties
      from the relative dehydration of their protoplasts. The spore cortex, a
      peptidoglycan structure surrounding the protoplasm, maintains, and is postulated
      to have a role in attaining, protoplast dehydration. A structural modification
      unique to the spore cortex is the removal of all or part of the peptide side
      chains from the majority of the muramic acid residues and the conversion of 50%
      of the muramic acid to muramic lactam. A mutation in the cwlD gene of Bacillus
      subtilis, predicted to encode a muramoyl-L-alanine amidase, results in the
      production of spores containing no muramic lactam. These spores have normally
      dehydrated protoplasts but are unable to complete the germination/ outgrowth
      process to produce viable cells. Addition of germinants resulted in the
      triggering of germination with loss of spore refractility and the release of
      dipicolinic acid but no degradation of cortex peptidoglycan. Germination in the
      presence of lysozyme allowed the cwlD spores to produce viable cells and showed
      that they have normal heat resistance properties. These results (i) suggest that
      a mechanical activity of the cortex peptidoglycan is not required for the
      generation of protoplast dehydration but rather that it simply serves as a static
      structure to maintain dehydration, (ii) demonstrate that degradation of cortex
      peptidoglycan is not required for spore solute release or partial spore core
      rehydration during germination, (iii) indicate that muramic lactam is a major
      specificity determinant of germination lytic enzymes, and (iv) suggest the
      mechanism by which the spore cortex is degraded during germination while the germ
      cell wall is left intact.

PMID- 8986825
TI  - A novel host factor for integration of mycobacteriophage L5.
AB  - Bacterial integration host factors (IHFs) play central roles in the cellular
      processes of recombination, DNA replication, transcription, and bacterial
      pathogenesis. We describe here a novel mycobacterial IHF (mIHF) of Mycobacterium
      smegmatis and Mycobacterium tuberculosis that stimulates integration of
      mycobacteriophage L5. mIHF is the product of a single gene and is unrelated at
      the sequence level to other integration host factors. By itself, mIHF does not
      bind preferentially to attP DNA, although it significantly alters the pattern of
      integrase (Int) binding, promoting the formation of specific integrase-mIHF-attP
      intasome complexes.

PMID- 8986826
TI  - Functional reorganization in thalamocortical networks: transition between
      spindling and delta sleep rhythms.
AB  - Thalamic reticularis, thalamocortical, and cortical cells participate in the 7-14
      hz spindling rhythm of early sleep and the slower delta rhythms of deeper sleep,
      with different firing patterns. In this case study, showing the interactions of
      intrinsic and synaptic properties, a change in the conductance of one kind of
      cell effectively rewires the thalamocortical circuit, leading to the transition
      from the spindling to the delta rhythm. The two rhythms make different uses of
      the fast (GABAA) and slow (GABAB) inhibition generated by the thalamic
      reticularis cells.

PMID- 8986827
TI  - Nitric oxide-related species inhibit evoked neurotransmission but enhance
      spontaneous miniature synaptic currents in central neuronal cultures.
AB  - Nitric oxide (NO.) does not react significantly with thiol groups under
      physiological conditions, whereas a variety of endogenous NO donor molecules
      facilitate rapid transfer to thiol of nitrosonium ion (NO+, with one less
      electron than NO.). Here, nitrosonium donors are shown to decrease the efficacy
      of evoked neurotransmission while increasing the frequency of spontaneous
      miniature excitatory postsynaptic currents (mEPSCs). In contrast, pure NO donors
      have little effect (displaying at most only a slight increase) on the amplitude
      of evoked EPSCs and frequency of spontaneous mEPSCs in our preparations. These
      findings may help explain heretofore paradoxical observations that the NO moiety
      can either increase, decrease, or have no net effect on synaptic activity in
      various preparations.

PMID- 8986828
TI  - A regenerative link in the ionic fluxes through the weaver potassium channel
      underlies the pathophysiology of the mutation.
AB  - The homozygous weaver mouse displays neuronal degeneration in several brain
      regions. Previous experiments in heterologous expression systems showed that the
      G protein-gated inward rectifier K+ channel (GIRK2) bearing the weaver pore
      region GYG-to-SYG mutation (i) is not activated by G beta gamma subunits, but
      instead shows constitutive activation, and (ii) is no longer a K(+)-selective
      channel but conducts Na+ as well. The present experiments on weaverGIRK2
      (wvGIRK2) expressed in Xenopus oocytes show that the level of constitutive
      activation depends on intracellular Na+ concentration. In particular,
      manipulations that decrease intracellular Na+ produce a component of Na(+)
      permeable current activated via a G protein pathway. Therefore, constitutive
      activation may not arise because the weaver mutation directly alters the gating
      transitions of the channel protein. Instead, there may be a regenerative cycle of
      Na+ influx through the wvGIRK2 channel, leading to additional Na+ activation. We
      also show that the wvGIRK2 channel is permeable to Ca2+, providing an additional
      mechanism for the degeneration that characterizes the weaver phenotype. We
      further demonstrate that the GIRK4 channel bearing the analogous weaver mutation
      has properties similar to those of the wvGIRK2 channel, providing a glimpse of
      the selective pressures that have maintained the GYG sequence in nearly all known
      K+ channels.

PMID- 8986829
TI  - A novel heat-activated current in nociceptive neurons and its sensitization by
      bradykinin.
AB  - Pain differs from other sensations in many respects. Primary pain-sensitive
      neurons respond to a wide variety of noxious stimuli, in contrast to the
      relatively specific responses characteristic of other sensory systems, and the
      response is often observed to sensitize on repeated presentation of a painful
      stimulus, while adaptation is typically observed in other sensory systems. In
      most cases the cellular mechanisms of transduction and sensitization in response
      to painful stimuli are not understood. We report here that application of pulses
      of noxious heat to a subpopulation of isolated primary sensory neurons rapidly
      activates an inward current. The ion channel activated by heat discriminates
      poorly among alkali cations. Calcium ions both carry current and partially
      suppress the current carried by other ions. The current is markedly increased by
      bradykinin, a potent algogenic nonapeptide that is known to be released in vivo
      by tissue damage. Phosphatase inhibitors prolong the sensitization caused by
      bradykinin, and a similar sensitization is caused by activators of protein kinase
      C. We conclude that bradykinin sensitizes the response to heat by activating
      protein kinase C.

PMID- 8986830
TI  - Transforming neural computations and representing time.
AB  - Motifs of neural circuitry seem surprisingly conserved over different areas of
      neocortex or of paleocortex, while performing quite different sensory processing
      tasks. This apparent paradox may be resolved by the fact that seemingly different
      problems in sensory information processing are related by transformations
      (changes of variables) that convert one problem into another. The same basic
      algorithm that is appropriate to the recognition of a known odor quality,
      independent of the strength of the odor, can be used to recognize a vocalization
      (e.g., a spoken syllable), independent of whether it is spoken quickly or slowly.
      To convert one problem into the other, a new representation of time sequences is
      needed. The time that has elapsed since a recent event must be represented in
      neural activity. The electrophysiological hallmarks of cells that are involved in
      generating such a representation of time are discussed. The anatomical
      relationships between olfactory and auditory pathways suggest relevant
      experiments. The neurophysiological mechanism for the psychophysical logarithmic
      encoding of time duration would be of direct use for interconverting olfactory
      and auditory processing problems. Such reuse of old algorithms in new settings
      and representations is related to the way that evolution develops new
      biochemistry.

PMID- 8986831
TI  - Suppression of glucocorticoid secretion and antipsychotic drugs have similar
      effects on the mesolimbic dopaminergic transmission.
AB  - Specific antagonists of central dopaminergic receptors constitute the major class
      of antipsychotic drugs (APD). Two principal effects of APD are used as criteria
      for the pre-clinical screening of their antipsychotic action: (i) inhibition of
      basal and depolarization-induced activity of mesolimbic dopaminergic neurons;
      (ii) antagonism of the locomotor effects of dopaminergic agonists. Given that
      glucocorticoid hormones in animals increase dopamine release and dopamine
      mediated behaviors and that high levels of glucocorticoids can induce psychotic
      symptoms in humans, these experiments examined whether inhibition of endogenous
      glucocorticoids might have APD-like effects on mesolimbic dopaminergic
      transmission in rats. It is shown that suppression of glucocorticoid secretion by
      adrenalectomy profoundly decreased (by greater than 50%): (i) basal dopaminergic
      release and the release of dopamine induced by a depolarizing stimulus such as
      morphine (2 mg/kg, s.c.), as measured in the nucleus accumbens of freely moving
      animals by microdialysis; (ii) the locomotor activity induced by the direct
      dopaminergic agonist apomorphine. The effects of adrenalectomy were
      glucocorticoid specific given that they were reversed by the administration of
      glucocorticoids at doses within the physiological range. Despite its profound
      diminution of dopaminergic neurotransmission, adrenalectomy neither modified the
      number of mesencephalic dopaminergic neurons nor induced gliosis in the
      mesencephalon or in the nucleus accumbens, as shown by tyrosine hydroxylase and
      glial fibrillary acidic protein immunostaining. In conclusion, these findings
      suggest that blockade of central effects of glucocorticoids might open new
      therapeutic strategies of behavioral disturbances.

PMID- 8986832
TI  - Ca2+/calmodulin-dependent protein kinase II phosphorylation of the presynaptic
      protein synapsin I is persistently increased during long-term potentiation.
AB  - Long-term potentiation (LTP) is an increase in synaptic responsiveness thought to
      be involved in mammalian learning and memory. The localization (presynaptic
      and/or postsynaptic) of changes underlying LTP has been difficult to resolve with
      current electrophysiological techniques. Using a biochemical approach, we have
      addressed this issue and attempted to identify specific molecular mechanisms that
      may underlie LTP. We utilized a novel multiple-electrode stimulator to produce
      LTP in a substantial portion of the synapses in a hippocampal CA1 minislice and
      tested the effects of such stimulation on the presynaptic protein synapsin I. LTP
      inducing stimulation produced a long-lasting 6-fold increase in the
      phosphorylation of synapsin I at its Ca2+/calmodulin-dependent protein kinase II
      (CaM kinase II) sites without affecting synapsin I levels. This effect was fully
      blocked by either the N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5
      phosphonopentanoic acid (APV) or the CaM kinase II inhibitor KN-62. Our results
      indicate that LTP expression is accompanied by persistent changes in presynaptic
      phosphorylation, and specifically that presynaptic CaM kinase II activity and
      synapsin I phosphorylation may be involved in LTP expression.

PMID- 8986833
TI  - Recombinant scrapie-like prion protein of 106 amino acids is soluble.
AB  - The N terminus of the scrapie isoform of prion protein (PrPSc) can be truncated
      without loss of scrapie infectivity and, correspondingly, the truncation of the N
      terminus of the cellular isoform, PrPC, still permits conversion into PrPSc. To
      assess whether additional segments of the PrP molecule can be deleted, we
      previously removed regions of putative secondary structure in PrPC; in the
      present study we found that deletion of each of the four predicted helices
      prevented PrPSc formation, as did deletion of the stop transfer effector region
      and the C178A mutation. Removal of a 36-residue loop between helices 2 and 3 did
      not prevent formation of protease-resistant PrP; the resulting scrapie-like
      protein, designated PrPSc106, contained 106 residues after cleavage of an N
      terminal signal peptide and a C-terminal sequence for glycolipid anchor addition.
      Addition of the detergent Sarkosyl to cell lysates solubilized PrPSc106, which
      retained resistance to digestion by proteinase K. These results suggest that all
      the regions of proposed secondary structure in PrP are required for PrPSc
      formation, as is the disulfide bond stabilizing helices 3 and 4. The discovery of
      PrPSc106 should facilitate structural studies of PrPSc, investigations of the
      mechanism of PrPSc formation, and the production of PrPSc-specific antibodies.

PMID- 8986834
TI  - Arrest of neuronal migration by excitatory amino acids in hamster developing
      brain.
AB  - The influence of the excitotoxic cascade on the developing brain was investigated
      using ibotenate, a glutamatergic agonist of both N-methyl-D-aspartate (NMDA)
      ionotropic receptors and metabotropic receptors. Injected in the neopallium of
      the golden hamster at the time of production of neurons normally destined for
      layers IV, III, and II, ibotenate induces arrests of migrating neurons at
      different distances from the germinative zone within the radial migratory
      corridors. The resulting cytoarchitectonic patterns include periventricular
      nodular heterotopias, subcortical band heterotopias, and intracortical arrests of
      migrating neurons. The radial glial cells and the extracellular matrix are free
      of detectable damage that could suggest a defect in their guiding role. The
      migration disorders are prevented by coinjection of DL-2-amino-7-phosphoheptanoic
      acid, an NMDA ionotropic antagonist, but are not prevented by coinjection of L(+)
      2-amino-3-phosphonopropionic acid, a metabotropic antagonist. This implies that
      an excess of ionic influx through the NMDA channels of neurons alters the
      metabolic pathways supporting neuronal migration. Ibotenate, a unique molecular
      trigger of the excitotoxic cascade, produces a wide spectrum of abnormal neuronal
      migration patterns recognized in mammals, including the neocortical deviations
      encountered in the human brain.

PMID- 8986835
TI  - Regeneration of broken tip links and restoration of mechanical transduction in
      hair cells.
AB  - A hair cell's tip links are thought to gate mechanoelectrical transduction
      channels. The susceptibility of tip links to acoustic trauma raises questions as
      to whether these fragile structures can be regenerated. We broke tip links with
      the calcium chelator 1,2-bis(O-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid
      and found that they can regenerate, albeit imperfectly, over several hours. The
      time course of tip-link regeneration suggests that this process may underlie
      recovery from temporary threshold shifts induced by noise exposure. Cycloheximide
      does not block tip-link regeneration, indicating that new protein synthesis is
      not required. The calcium ionophore ionomycin prevents regeneration, suggesting
      regeneration normally may be stimulated by the reduction in stereociliary Ca2+
      when gating springs rupture and transduction channels close. Supporting the
      equivalence of tip links with gating springs, mechanoelectrical transduction
      returns over the same time period as tip links; strikingly, adaptation is
      substantially reduced, even 24 hr after breaking tip links.

PMID- 8986836
TI  - Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive
      weight gain in genetically obese Zucker rats and rats during nicotine withdrawal.
AB  - Elevation of the neuropeptide corticotropin-releasing factor (CRF) in the brain
      is associated with a reduction of food intake and body weight gain in normal and
      obese animals. A protein that binds CRF and the related peptide, urocortin, with
      high affinity, CRF-binding protein (CRF-BP), may play a role in energy
      homeostasis by inactivating members of this peptide family in ingestive and
      metabolic regulatory brain regions. Intracerebroventricular administration in
      rats of the high-affinity CRF-BP ligand inhibitor, rat/human CRF (6-33), which
      dissociates CRF or urocortin from CRF-BP and increases endogenous brain levels of
      "free" CRF or urocortin significantly blunted exaggerated weight gain in Zucker
      obese subjects and in animals withdrawn from chronic nicotine. Chronic
      administration of CRF suppressed weight gain nonselectively by 60% in both Zucker
      obese and lean control rats, whereas CRF-BP ligand inhibitor treatment
      significantly reduced weight gain in obese subjects, without altering weight gain
      in lean control subjects. Nicotine abstinent subjects, but not nicotine-naive
      controls, experienced a 35% appetite suppression and a 25% weight gain reduction
      following acute and chronic administration, respectively, of CRF-BP ligand
      inhibitor. In marked contrast to the effects of a CRF-receptor agonist, the CRF
      BP ligand inhibitor did not stimulate adrenocorticotropic hormone secretion or
      elevate heart rate and blood pressure. These results provide support for the
      hypothesis that the CRF-BP may function within the brain to limit selected
      actions of CRF and/or urocortin. Furthermore, CRF-BP may represent a novel and
      functionally selective target for the symptomatic treatment of excessive weight
      gain associated with obesity of multiple etiology.

PMID- 8986837
TI  - Sequence-specific antitumor activity of a phosphorothioate
      oligodeoxyribonucleotide targeted to human C-raf kinase supports an antisense
      mechanism of action in vivo.
AB  - To determine the mechanism of action responsible for the in vivo antitumor
      activity of a phosphorothioate antisense inhibitor targeted against human C-raf
      kinase (ISIS 5132, also known as CGP69846A), a series of mismatched
      phosphorothioate analogs of ISIS 5132 or CGP69846A were synthesized and
      characterized with respect to hybridization affinity, inhibitory effects on C-raf
      gene expression in vitro, and antitumor activity in vivo. Incorporation of a
      single mismatch into the sequence of ISIS 5132 or CGP69846A resulted in reduced
      hybridization affinity toward C-raf RNA sequences and reduced inhibitory activity
      against C-raf expression in vitro and tumor growth in vivo. Moreover,
      incorporation of additional mismatches resulted in further loss of in vitro and
      in vivo activity in a manner that correlated well with a hybridization-based
      (i.e., antisense) mechanism of action. These results provide important
      experimental evidence supporting an antisense mechanism of action underlying the
      in vivo antitumor activity displayed by ISIS 5132 or CGP69846A.

PMID- 8986838
TI  - Domains of P2X receptors involved in desensitization.
AB  - ATP-gated ion channels (P2X receptors) are abundantly expressed in both neuronal
      and nonneuronal tissues, where they can serve as postsynaptic receptors. The
      response to ATP shows marked desensitization in some tissues but not others.
      Currents induced by ATP in Xenopus oocytes expressing cloned P2X1 (or P2X3)
      receptor had strong desensitization, whereas currents in cells expressing P2X2
      receptors desensitized relatively little (90% vs. 14% decline of current in a 10
      s application). In chimeric receptors, substitution into the P2X1 receptor of
      either one of two 34-residue segments from the P2X2 receptor removed the
      desensitization; these segments included the first or the second hydrophobic
      domain. In contrast, desensitization was introduced into the P2X2 receptor only
      by providing both these segments of the P2X1 (or P2X3) receptor. This suggests
      that desensitization requires interaction between the two hydrophobic domains of
      the receptor, and supports the view that these are membrane-spanning segments.

PMID- 8986839
TI  - Integration of circadian and phototransduction pathways in the network
      controlling CAB gene transcription in Arabidopsis.
AB  - The transcription of CAB genes, encoding the chlorophyll a/b-binding proteins, is
      rapidly induced in dark-grown Arabidopsis seedlings following a light pulse. The
      transient induction is followed by several cycles of a circadian rhythm.
      Seedlings transferred to continuous light are known to exhibit a robust circadian
      rhythm of CAB expression. The precise waveform of CAB expression in light-dark
      cycles, however, reflects a regulatory network that integrates information from
      photoreceptors, from the circadian clock and possibly from a developmental
      program. We have used the luciferase reporter system to investigate CAB
      expression with high time resolution. We demonstrate that CAB expression in light
      grown plants exhibits a transient induction following light onset, similar to the
      response in dark-grown seedlings. The circadian rhythm modulates the magnitude
      and the kinetics of the response to light, such that the CAB promoter is not
      light responsive during the subjective night. A signaling pathway from the
      circadian oscillator must therefore antagonize the phototransduction pathways
      controlling the CAB promoter. We have further demonstrated that the phase of
      maximal CAB expression is delayed in light-dark cycles with long photoperiods,
      due to the entrainment of the circadian oscillator. Under short photoperiods,
      this pattern of entrainment ensures that dawn coincides with a phase of high
      light responsiveness, whereas under long photoperiods, the light response at dawn
      is reduced.

PMID- 8986840
TI  - Molecular recognition of pathogen attack occurs inside of plant cells in plant
      disease resistance specified by the Arabidopsis genes RPS2 and RPM1.
AB  - The Arabidopsis thaliana disease resistance genes RPS2 and RPM1 belong to a class
      of plant disease resistance genes that encode proteins that contain an N-terminal
      tripartite nucleotide binding site (NBS) and a C-terminal tandem array of leucine
      rich repeats. RPS2 and RPM1 confer resistance to strains of the bacterial
      phytopathogen Pseudomonas syringae carrying the avirulence genes avrRpt2 and
      avrB, respectively. In these gene-for-gene relationships, it has been proposed
      that pathogen avirulence genes generate specific ligands that are recognized by
      cognate receptors encoded by the corresponding plant resistance genes. To test
      this hypothesis, it is crucial to know the site of the potential molecular
      recognition. Mutational analysis of RPS2 protein and in vitro
      translation/translocation studies indicated that RPS2 protein is localized in the
      plant cytoplasm. To determine whether avirulence gene products themselves are the
      ligands for resistance proteins, we expressed the avrRpt2 and avrB genes directly
      in plant cell using a novel quantitative transient expression assay, and found
      that expression of avrRpt2 and avrB elicited a resistance response in plants
      carrying the corresponding resistance genes. This observation indicates that no
      bacterial factors other than the avirulence gene products are required for the
      specific resistance response as long as the avirulence gene products are
      correctly localized. We propose that molecular recognition of P. syringae in RPS2
      and RPM1-specified resistance occurs inside of plant cells.

PMID- 8986842
TI  - When the brain changes its mind: interocular grouping during binocular rivalry.
AB  - The prevalent view of binocular rivalry holds that it is a competition between
      the two eyes mediated by reciprocal inhibition among monocular neurons. This view
      is largely due to the nature of conventional rivalry-inducing stimuli, which are
      pairs of dissimilar images with coherent patterns within each eye's image. Is it
      the eye of origin or the coherency of patterns that determines perceptual
      alternations between coherent percepts in binocular rivalry? We break the
      coherency of conventional stimuli and replace them by complementary patchworks of
      intermingled rivalrous images. Can the brain unscramble the pieces of the
      patchwork arriving from different eyes to obtain coherent percepts? We find that
      pattern coherency in itself can drive perceptual alternations, and the patchworks
      are reassembled into coherent forms by most observers. This result is in
      agreement with recent neurophysiological and psychophysical evidence
      demonstrating that there is more to binocular rivalry than mere eye competition.

PMID- 8986843
TI  - Progressive entorhinal cortex lesions accelerate hippocampal sprouting and spare
      spatial memory in rats.
AB  - Accelerating hippocampal sprouting by making unilateral progressive lesions of
      the entorhinal cortex spared the spatial memory of rats tested for retention of a
      learned alternation task. Subsequent transection of the sprouted crossed
      temporodentate pathway (CTD), as well as a simultaneous CTD transection and
      progressive entorhinal lesion, produced a persistent deficit on the memory task.
      These results suggest that CTD sprouting, which is homologous to the original
      perforant path input to the dentate gyrus of the hippocampus, is behaviorally
      significant and can ameliorate at least some of the memory deficits associated
      with hippocampal deafferentation.

PMID- 8986845
TI  - Pedantic speaking style differentiates Asperger syndrome from high-functioning
      autism.
AB  - Asperger syndrome (AS) is a pervasive developmental disorder recently introduced
      as a new diagnostic category in the ICD-10 and the DSM-IV. Along with motor
      clumsiness, pedantic speech has been proposed as a clinical feature of AS.
      However, few attempts have been made to define and measure this symptom. We
      studied 17 patients with AS (ICD-10; 14 male, 3 female; mean age 16.4 years, mean
      full-scale IQ 97) and compared them with a control group of 13 patients with
      normal-intelligence autism or high-functioning autism (HFA) (ICD-10/DSM-III-R; 12
      male, 1 female; mean age 15.5 years, mean full-scale IQ 81.2). An operational
      definition of pedantic speech was formulated and a rating scale devised. 13 (76%)
      of the AS patients were rated as pedantic compared to 4 (31%) of the HFA group
      (chi 2 = 6.3; p = .01). Results suggest that pedantic speech is common in AS and
      may help differentiate AS from high-functioning autism.

PMID- 8986846
TI  - Hand preference and hand skill in children with autism.
AB  - Hand preference and hand skill was assessed in two broad age groups of children
      with autism, children with learning disabilities, and control schoolchildren. The
      first group comprised children ages 3-5 years and the second group of children
      ages 11-13 years. Degree of handedness remained relatively stable across age
      groups, particularly within the autistic and learning-disabled populations. The
      main difference was between the subject groups, with the normal controls more
      lateralized than either the children with autism or children with learning
      disabilities. As with degree of handedness, consistency of handedness also
      differed significantly between subject groups with the normal controls more
      consistent in their hand preference than the other two groups. In addition,
      younger children were less consistent in their hand preference than older
      children. However, the present study found no evidence of a dissociation of hand
      skill and hand preference in children with autism compared to children with
      learning disabilities and normal developing children.

PMID- 8986847
TI  - Adaptive and intellectual functioning in autistic and nonautistic retarded
      children.
AB  - This study examined the relationship between adaptive functioning on the Vineland
      Adaptive Behaviour Scale (VABS) and intellectual functioning on the Stanford
      Binet Intelligence Scale, 4th edition (SB-IV) in autistic children and
      nonautistic retarded children of comparable CA and SB-IV composite score (IQ).
      The autistic group had lower scores than the retarded group in VABS adaptive
      composite, Socialization domain, and Communication domain, and SB-IV Verbal
      Reasoning area. VABS domain scores yielded higher classification rates than the
      SB-IV area scores in discriminating the two groups. Correlations between the two
      measures were much higher for the autistic group than for the retarded group.
      Results support the conclusion that the cognitive impairment in autism is
      reflected in greater impairment in adaptive behaviors than in mental retardation
      without autism.

PMID- 8986848
TI  - The autism survey: an evaluation of reliability and validity.
AB  - Psychometric properties of the Autism Survey, an instrument designed to assess
      respondents' knowledge about autism, were evaluated. Subjects completed the
      survey at a training conference and again 1 month later. Confirmatory factor
      analysis indicated that the survey measures one factor. With respect to
      reliability, the Autism Survey proved to be stable across time, and the total
      score was internally consistent. A few rogue items were recommended for deletion.
      Further analyses support the validity of the instrument.

PMID- 8986849
TI  - Case study: cross-gender preoccupations with two male children with autism.
AB  - Persons with autism frequently exhibit circumscribed interests and unusual
      preoccupations. In this case study, two young males with autism are presented who
      have preoccupations with feminine gender-stereotyped activities and objects.
      These types of preoccupations in children with autism have not been reported in
      the literature, but may be more prevalent than realized due to parental
      underreporting given the negative stigma associated with feminine interests in
      young boys. The development of gender identity in young children with autism has
      rarely been addressed in the literature. It seems unlikely that these two cases
      can be categorized as gender identity disorders. Understanding these
      preoccupations in the context of autism rather than focusing on the gender
      identity issues has important implications for treatment. These cases point to
      the need for further study of the complex interplay of environmental and
      neurobiologic factors affecting gender identity roles and preoccupations in
      autism.

PMID- 8986850
TI  - Brief report: the effects of typed and spoken modality combinations on the
      language performance of adults with autism.

PMID- 8986851
TI  - Brief report: two case studies using virtual reality as a learning tool for
      autistic children.
AB  - The children complied with most requests. Some of our teaching goals were limited
      by technology or space while others were limited by the difficulty of presenting
      a task to the children in a way that was understandable within their environment.
      However, the opportunity to introduce this technology to children was an
      important first step in exploring the potential VR offers to understanding the
      perceptual processes involved in autism. Our results indicate that the will
      accept a VR helmet and wear it, identify familiar objects and qualities of these
      objects in their environment while using the helmet, and locate and move toward
      objects in their environment while wearing the helmet. More research is necessary
      to verify the potential in this area, especially to discover if learning
      experiences through VR generalize to other environments, but it appears virtual
      reality may provide a useful tool for furthering our understanding of autism and
      guiding efforts at treatment and intervention.

PMID- 8986852
TI  - Brief report: physiognomic perception in autism.

PMID- 8986853
TI  - Is the prevalence of autism increasing?

PMID- 8986854
TI  - [Acute myocardial infarction in young Japanese women].
AB  - Women appear to be protected, until the menopause, from the development of
      coronary artery disease. The incidence of acute myocardial infarction in young
      women is very low, so there is little information on the etiology, clinical
      features, and prognosis for such patients. We studied 24 young female patients
      with acute myocardial infarction (< 50 years) among 2,457 consecutive patients
      with acute myocardial infarction admitted to the coronary care unit of the
      National Cardiovascular Center from December 1977 through August 1994. Their
      clinical features and in-hospital mortality were compared with 100 consecutive
      young male patients (< 50 years) with acute myocardial infarction. The fraction
      of patients of age younger than 50 years among all age groups was lower in female
      than in male acute myocardial infarction patients (5% vs 13%, p < 0.01). The
      increase of the coronary risk factors, hypercholesterolemia (25% vs 55%, p <
      0.05) and cigarette smoking (17% vs 96%, p < 0.05) were less common in women. In
      female patients, the serum total cholesterol level was lower (195 +/- 50 vs 216
      +/- 48 mg/dl, p = 0.06), and the serum high-density lipoprotein cholesterol level
      was higher (50 +/- 12 vs 39 +/- 12 mg/dl, p < 0.05) than in male patients. Other
      risk factors did not differ significantly between the two groups. Angiography 1
      month after myocardial infarction showed fewer diseased coronary arteries (> 75%
      stenosis) in female than male patients (0.8 +/- 0.9 vs 1.8 +/- 1.0, p < 0.01),
      and normal coronary arteries were seen in 35% of female patients (male 6%, p <
      0.05). Ten female patients (42%) had obviously non-atherosclerotic causes of
      acute myocardial infarction: Takayasu aortitis in three patients, coronary
      embolism in two, acute dissection of the aorta in two, and idiopathic coronary
      artery dissection, Kawasaki disease, and systemic lupus erythematosus in one
      each. In contrast, among male patients, only one had coronary embolism (1%). In
      hospital mortality was higher in women (17%) than in men (2%, p < 0.05). Young
      female patients (< 50 years) with acute myocardial infarction have a low
      incidence of hyperlipidemia and normal coronary arteries or involvement of the
      left main trunk are more common compared with male patients (< 50 years).
      Although 42% of female patients had obvious non-atherosclerotic etiology of acute
      myocardial infarction, the causes varied widely.

PMID- 8986855
TI  - Safety and effectiveness of exercise training in patients with silent myocardial
      ischemia.
AB  - The effectiveness of exercise training in patients with silent myocardial
      ischemia was examined. Forty patients with coronary heart disease (mean age 55 +/
      8 years) were recruited for a 12-week exercise training program. All patients
      underwent treadmill exercise stress testing, exercise thallium-201 single photon
      emission computed tomography and left heart catheterization. They were divided
      into three groups based on the symptoms and the results of exercise thallium
      scintigraphy, i.e., painful myocardial ischemia (PMI group), silent myocardial
      ischemia (SMI group), and non-myocardial ischemia (NMI group). Normalized
      treadmill time was longer in the SMI group (108 +/- 24%) than in the PMI group
      (86 +/- 14%, p < 0.05). All 40 patients, 14 from the PMI group, 16 from the SMI
      group and 10 from the NMI group, completed the whole exercise training program. A
      significant prolongation of treadmill time was attained in all three groups after
      exercise training [PMI group: from 494 +/- 105 to 632 +/- 78 sec (p < 0.05), SMI
      group: from 609 +/- 147 to 746 +/- 137 sec (p < 0.05), NMI group: from 572 +/-
      112 to 739 +/- 13 sec (p < 0.05)]. The improvement of myocardial ischemia
      following exercise training was similar in the SMI and PMI groups. No adverse
      effects were detected throughout the program. The exercise training program
      adopted in this study proved safe and effective in patients with silent
      myocardial ischemia.

PMID- 8986856
TI  - [Clinical characteristics of pulmonary embolism without definitive predisposing
      factors].
AB  - Patients with pulmonary embolism may have no definitive predisposing factors for
      thrombi. The clinical entity of chronic pulmonary embolism is also uncertain.
      This study clarified the clinical characteristics of pulmonary embolism without
      definitive predisposing factors. During the last 10 years, 36 consecutive
      patients were diagnosed as having pulmonary embolism (mean age 61 years, female
      75%). Twenty-four patients (67%) had definitive predisposing factors
      ("definitive" group). Patients without definitive predisposing factors had the
      following characteristics. The onset of symptoms was out-hospital and insidious.
      The main symptom was exertional dyspnea without acute episode compatible with an
      embolism. In four patients (33%) there was a delay of over 2 years form the onset
      of symptoms to the diagnosis. Three patients had been treated for depression.
      Thrombolytic therapy caused an inadequate fall in mean pulmonary artery pressure
      from 41 +/- 11 to 24 +/- 8 mmHg and in three patients it remained over 30 mmHg.
      Deep vein thrombosis were found in four of nine patients in whom venography were
      performed 10 days after thrombolytic therapy, but only one patient showed
      thrombus in the "definitive" group. During the convalescent stage, all patients
      were treated with prophylactic warfarin. Home oxygen therapy was indicated in
      three patients and an inferior vena caval filter was implanted in two patients.
      One third of patients with pulmonary embolism in our institute had no definitive
      predisposing factors. In these patients, even with thrombolytic therapy, recovery
      of pulmonary hypertension was often insufficient and deep vein thrombosis
      persisted. Clinicians should be aware of this disease to avoid undue delay in its
      diagnosis.

PMID- 8986858
TI  - [Automatic assessment of left ventricular cavity area by the automated contour
      tracking method].
AB  - Measurements of left ventricular cavity area by the manual tracing method from
      apical four-chamber views were compared with those using the automated contour
      tracking (ACT) method. Nine consecutive patients in whom clear images were
      obtained by two-dimensional echocardiography were studied, and left ventricular
      end-diastolic, end-systolic areas an fractional area changes were calculated
      using the ACT method. The ACT method slightly underestimated left ventricular
      cavity areas, but excellent correlations were obtained with left ventricular end
      diastolic and end-systolic areas between the ACT and manual methods (r = 0.99,
      SEE = 1.5 cm2; r = 0.99, SEE = 1.2 cm2; respectively). Manual tracing fractional
      area change correlated well with that by the ACT method (r = 0.95, SEE = 3.4%).
      The ACT method provides accurate estimates of the area of the left ventricular
      cavity.

PMID- 8986857
TI  - [Left ventricular lesions in arrhythmogenic right ventricular dysplasia and 12
      lead electrocardiographic findings].
AB  - Left ventricular lesions in arrhythmogenic right ventricular dysplasia have not
      been well described, and the relationship between the left ventricular lesions
      and the 12-lead electrocardiographic findings has not been analyzed. This study
      examined whether the presence of left ventricular lesions and the extent of right
      ventricular lesions due to arrhythmogenic right ventricular dysplasia are
      predictable by 12-lead electrocardiographic findings. The 12-lead
      electrocardiograms during sinus rhythm and left and right ventriculography were
      studied in 29 patients (27 males and 2 females, mean age 42.6 +/- 15.5 years)
      diagnosed by the current criteria for this disease. After evaluation, patients
      were divided into two groups: those with normal left ventricles (normal group)
      and those with left ventricular wall motion abnormalities (abnormal group).
      Seventeen of the 29 patients (59%) were classified into the abnormal group. Left
      ventricular wall motion abnormalities were located in the posterolateral (4
      patients), apical (1), and posterolateral and apical regions (12). QS patterns of
      abnormal Q waves in lead I, aVL or V5, V6 rS patterns (R/S ratio < 1) in leads I
      and V6, and/or R or Rs patterns (R/S ratio > 1) in lead V1 were observed in all
      patients in the abnormal group, but in none in the normal group. There was a
      positive correlation between the right ventricular end-diastolic volume index and
      the number of precordial negative T waves (r = 0.746, p < 0.0001), and the time
      from onset of the QRS to the terminal portion of the epsilon wave in lead V1 (r =
      0.627, p < 0.001). The correlation coefficients showed no significant differences
      between the groups. A left ventricular lesion associated with arrhythmogenic
      right ventricular dysplasia was not unusual (59%), and our study suggests that
      the posterolateral and apical regions are the most frequent sites. The presence
      of these lesions were predictable by the QRS abnormalities. Moreover, regardless
      of the presence of such a lesion, the extent of the right ventricular lesion is
      also predictable by the 12-lead electrocardiographic findings.

PMID- 8986859
TI  - [Partial rupture progressing to complete rupture of the left ventricular anterior
      papillary muscle after acute myocardial infarction: a case report].
AB  - A 71-year old man presented with partial rupture progressing to complete rupture
      of the left ventricular anterior papillary muscle after acute anterolateral
      myocardial infarction. The progressive rupture was demonstrated by transthoracic
      and transesophageal echocardiography. Transthoracic echocardiography showed
      exaggerated systolic prolapse of the anterior mitral leaflet with grade III
      mitral regurgitation and partial disruption of the anterolateral papillary
      muscle, but transesophageal echocardiography during surgery disclosed the
      progression of the partial rupture to complete rupture. The flail anterior mitral
      leaflet with severe mitral regurgitation and the head of the ruptured papillary
      muscle into the left atrium in systole were confirmed. The patient was treated by
      coronary artery bypass grafting and mitral valve prosthesis using a St. Jude
      Medical valve with good outcome.

PMID- 8986860
TI  - [A 42-year-old woman with cardiac tumor and tamponade].

PMID- 8986861
TI  - [Stethoscope: an Egyptian mystery].

PMID- 8986862
TI  - Thrombotic thrombocytopenic purpura: evolution across 15 years.
AB  - Thrombotic thrombocytopenic purpura (TTP) was originally described 70 years ago.
      It is considered an uncommon disorder with a reported occurrence rate of one case
      per 1 million patients. Mortality has decreased from almost 100% early on to 30
      50% with the advent of newer treatment methods. We reviewed 41 patients with a
      diagnosis of TTP spanning the years 1980 to mid 1994. We found a much higher case
      rate, one per 6000 hospital admissions, and an overall death rate of 40%.
      However, isolating 5 year periods we noted a marked fall in mortality from 54%
      (1980-1984), 44% (1985-1989), to 18% (1990-1994). Previous reports describe
      relapsing TTP and report an incidence of 7-15% although very recent data suggests
      a higher incidence. In our study, we found an overall relapse rate of 25% and by
      5 year periods 23% (1980-1984), 13% (1985-1989), and 46% (1990-1994). We suggest
      that the improvement in survival and the increase in relapse rate are related and
      reflect more effective therapy for this once almost always fatal disease.
      Patients now survive their initial episode and thus are at risk for recurrence.
      Identification of risk factors for relapse will require further study.

PMID- 8986863
TI  - Apheresis in grade 4 bone marrow transplant associated thrombotic
      microangiopathy: a case series.
AB  - Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) ranges in
      severity from a self-limited to a fatal disorder. There has been no specific
      therapy for this condition. We have previously described a clinical grading
      system for BMT-TM, based upon lactate dehydrogenase level (LDH) and percentage
      fragmented cells (FC) as follows: grade 0, normal or increases LDH and % FC < or
      = to 1.2%; grade 1, normal LDH and FC > or = to 1.3%; grade 2, increases LDH and
      FC = 1.3-4.8%; grade 3, increases LDH and FC = 4.9-9.6%; and grade 4, increases
      LDH and FC > or = to 9.7%. Patients with grade 4 BMT-TM usually have fulminant
      disease and generally succumb. This study summarizes results using a variety of
      apheresis procedures in a series of 16 patients with grade 4 BMT-TM. The
      apheresis procedures consisted of plasma exchange (with replacement with fresh
      frozen plasma or cryo-poor plasma), and protein A immunoadsorption (PAI). The PAI
      exchanges were not done concurrently with plasma exchange procedures. Fifteen
      patients had undergone an allogeneic BMT and the 16th patient had undergone an
      autologous peripheral blood stem cell transplant. Half showed hematologic
      improvement with a downstaging of their TM to grades 1-3. All non-responders died
      a median of 11 days following the onset of grade 4 BMT-TM. The median survival in
      the responders was significantly (P = 0.001) increased to 218 days with three
      responders surviving more than 400 days following the onset of this severe
      complication. These results suggest a role for apheresis in the treatment of this
      lethal complication. Nevertheless grade 4 BMT-TM represents a major complication
      of BMT; the median survival in this group of 16 patients with grade 4 BMT-TM was
      only 31 days.

PMID- 8986864
TI  - Successful collection and transplantation of peripheral blood stem cells in
      cancer patients using large-volume leukaphereses.
AB  - It was the aim of our study to determine the collection efficiency and yield of
      CD34+ cells in 88 cancer patients (pts, 44 males/44 females) who underwent 154
      large-volume leukaphereses (LV-LPs). The diagnoses were as follows: 18 patients
      had Non-Hodgkin's lymphoma, 9 Hodgkin's disease, 24 multiple myeloma, 6 acute
      leukemia, 27 breast cancer, and 4 patients had solid tumors of different types.
      During the course of LV-LPs, 20 liters (1) of blood were processed at a median
      flow-rate of 85 ml/min (CS 3000 Baxter) and 130 ml/min (COBE Spectra),
      respectively. Peripheral blood stem cells (PBSC) were collected following
      granulocyte colony-stimulating factor (G-CSF)-supported cytotoxic chemotherapy. A
      31% and 21% mean decrease in the platelet and white blood count was noted at the
      end of the LV-LPs when compared with the pre-leukapheresis values. The aphereses
      were well tolerated without adverse effects. The level of circulating CD34+ cells
      was closely related to the number of CD34+ cells contained in the respective
      leukapheresis product (R = 0.89, P < 0.001). Compared with 270 patients who
      underwent 838 regular 10 1 LPs, the yield of CD34+ cells/kg was almost two-fold
      greater (4.84 +/- 0.63 x 10(6) [Mean +/- SEM] vs. 2.60 +/- 0.16 x 10(6), P <
      0.001). The antigenic profile of CD34+ cells was assessed in 54 separate products
      collected on the occasion of 27 LV-LPs following the processing of 10 1 and 20 1,
      respectively. The intra-individual comparison included differentiation- as well
      as lineage-associated markers (CD38, Thy-1, c-kit, CD33, CD45RA). No difference
      in the subset composition was observed between the first and second product,
      arguing against a preferential release of particular CD34+ cell subsets during
      the procedure. As shown by molecular biological or immunocytochemical
      examination, the likelihood of harvesting malignant cells using large-volume
      aphereses was not increased in comparison with regular leukaphereses. Single
      harvests of > or = 2.5 x 10(6) CD34+ cells/kg could be obtained in 74% of the
      patients, compared with 52% in case of regular LPs. As the majority of patients
      were autografted with more than 2.5 x 10(6) CD34+ cells/kg following high-dose
      therapy, hematological recovery in general was rapid and not related to the type
      of apheresis product used. Considering patient comfort and savings in resource
      utilization, large-volume leukaphereses have become the standard procedure for
      PBSC collection in our center.

PMID- 8986865
TI  - Pediatric large volume peripheral blood progenitor cell collections from patients
      under 25 kg: a primer.
AB  - Collection of peripheral blood progenitor cells from small pediatric patients
      provides many social and technical challenges not faced when collecting from
      adult patients. This paper provides a single institutions experience with 85
      collections from 14 patients less than 25 kg of weight over a 2 year period.
      Specific challenges include obtaining venous access, anticoagulation, volume
      shifts, and obtaining patient cooperation. A systematic analysis of options for
      access, alternative modes of anticoagulation, and the effect of large ratios of
      extra-corporeal volume to patient's blood volume are discussed. Access uniformly
      required central venous catheters (CVC) ranging from 7-10 Fr. Anticoagulation
      included systemic heparinization titrating dose by activated clotting time in all
      cases and combined with citrate at a ratio of 1:25-1:30 in most cases.
      Collections were performed on a COBE Spectra, after priming with leukoreduced
      irradiated red cells and omitting both the initial 120cc diversion and rinse back
      of red cells at the end. Social challenges include issues of assent and ability
      to distract patients for the duration of a prolonged collection. Progenitor
      yields from collections from 14 patients were quantitated by CD34+ assay in all
      cases and CFU-GM in ten of 14 patients. A median of 4.5 x 10(6)/kg CD34+ cells
      were obtained for each collection. Complications, including those related to
      catheter access, are enumerated. In summary, large volume peripheral blood
      progenitor collection can be safely and efficaciously performed in small
      pediatric patients.

PMID- 8986866
TI  - Prevention of citrate reactions during therapeutic plasma exchange by constant
      infusion of calcium gluconate with the return fluid.
AB  - We have examined the effectiveness of intravenous calcium gluconate infusion in
      the prevention of citrate reactions during therapeutic plasma exchange. Over 3
      years, 636 procedures were performed on 90 patients, mostly for treatment of
      neurological disorders. Return fluid consisted of 4-5% human serum albumin in
      0.9% NaCl. Anticoagulant ACD-A was used at a starting ratio of 1:16. Whole blood
      flow rates were 70-80 ml/min. Treatments were divided into three groups for
      management of citrate reactions: Group A (360 treatments) were managed using
      simple measures only, including slowing the whole blood flow rate, altering the
      ACD:whole blood flow ratio, and oral calcium carbonate wafers; Group B (102
      treatments) received small intravenous boluses of 10% calcium gluconate, us to 25
      ml during the procedure; Group C (174 treatments) received constant infusion of
      calcium gluconate (10 ml/liter of return fluid) during the procedure. Citrate
      reactions occurred in 35.6% of Group A and 29.4% of Group B treatments (P = 0.3),
      but in only 8.6% of Group C treatments (P < 0.0001). Men with and without
      reactions were the same age (mean 63.3 vs. 61 years, P = 0.0823), but women with
      reactions were younger than women without reactions (mean 49.9 vs. 57.9 years, P
      < 0.0001). Supplementation of the return fluid with calcium gluconate is an
      effective, convenient, and well-tolerated method for prevention of citrate
      toxicity during therapeutic plasma exchange procedures using albumin-based return
      fluid.

PMID- 8986867
TI  - Anti-dsDNA antibody kinetics during in vivo apheresis in systemic lupus
      erythematosus patients and in an in vitro apheresis model.
AB  - Levels of anti-dsDNA measured just after an immunoadsorption procedure in
      systemic lupus erythematosus (SLE) patients are sometimes paradoxically larger
      than those measured just before the procedure. A 1:100 in vitro single
      compartment immunoadsorption system model was devised to determine which of two
      models, one- or two-compartment, more closely approximates the kinetics of anti
      dsDNA during apheresis procedures. Ten SLE patients were employed in this study.
      A total of 4,100 ml of plasma was passed through the dextran sulfate cellulose
      columns during one clinical apheresis session. In eight of ten patients, the log
      of RIA-measured anti-dsDNA titers decreased linearly as treated plasma volume
      increased, in both the clinical procedure and the experimental model. The mean
      adsorption efficacy in the clinical apheresis procedure and in the in vitro model
      was 0.37 and 0.27, respectively. However, in one patient the RIA-measured level
      of anti-dsDNA increased during the apheresis procedure; this phenomenon was
      mirrored in the model (definitely a single pool model). In contrast, the level of
      anti-dsDNA, as measured by ELISA, decreased in accordance with the increase of
      treated plasma volume in both the clinical and the in vitro apheresis procedures.
      Therefore, an increased titer of anti-dsDNA as measured by RIA immediately
      following clinical apheresis cannot be accounted for exclusively by an inflow of
      antibodies from a secondary (extravascular) pool into the circulating plasma. In
      short, a one-compartment model is applicable and an explanation must be sought
      elsewhere.

PMID- 8986868
TI  - Evidence for supporting cell proliferation and hair cell differentiation in the
      basilar papilla of adult Belgian Waterslager canaries (Serinus canarius).
AB  - We used the bromodeoxyuridine technique to study the proliferative activity in
      the basilar papilla of normal and Belgian Waterslager canaries with and without
      preceding sound trauma. Without sound trauma, there were, on average, six
      supporting cell divisions per day in the basilar papilla of Waterslager canaries.
      This rate of supporting cell proliferation corresponds well with estimates of the
      rate of hair cell differentiation derived from counts of immature-appearing hair
      cells obtained by using scanning electron microscopy of the Waterslager basilar
      papilla. Thus, supporting cell division appeared correlated with hair cell
      differentiation in Waterslager canaries. Bromodeoxyuridine labeling of cells in
      undamaged non-Waterslager canaries also indicated a very low rate of supporting
      cell division. In contrast with Waterslager canaries, this low rate of
      proliferation was not associated with a measurable rate of hair cell
      differentiation. In both normal and Waterslager canaries, exposure to
      traumatizing sound induced a dramatic increase in the rate of cell proliferation.
      These data show that a very low rate of supporting cell proliferation is normally
      present in birds, but it is not associated with a corresponding rate
      differentiation of hair cells. Only an increase above this low ambient rate of
      supporting cell proliferation, such as that following loss of hair cells, induces
      the differentiation of new hair cells in birds. The reason why Waterslager
      canaries do not completely compensate for their inherited hair cell deficit of
      30% is not clear, when they can clearly respond to additional cochlear trauma
      from noise exposure with an increase in proliferation rate.

PMID- 8986869
TI  - Dimensions and density of dendritic spines from rat dentate granule cells based
      on reconstructions from serial electron micrographs.
AB  - In the hippocampus, most excitatory synapses are located on dendritic spines. It
      has been postulated that the geometry of spines and/or postsynaptic density (PSD)
      influences synaptic efficiency and may contribute to the expression of plastic
      processes such as learning or long-term potentiation (LTP). Based on three
      dimensional reconstructions of dentate granule cell dendrites from serial
      electron micrographs, we have measured head dimensions, neck cross-sectional
      areas, neck length, and PSD area and form of 115 spines of dentate granule cells
      in the medial perforant path termination zone. All dimensions showed a large
      variability, with up to 100-fold differences in values. A calculated diffusion
      index for transport of molecules through the reconstructed neck varied over a 100
      fold range. The neck and head dimensions were moderately positively correlated,
      whereas the PSD area was strongly correlated with head volume. Distribution
      histograms and scatter plots of various spine dimensions did not reveal any
      systematic clustering, suggesting that there is a continuum of spine geometries
      rather than distinct classes for granule cell dendritic spines in the middle
      molecular layer. Transversely (n = 13) and longitudinally (n = 27) sectioned
      dendrites had mean spine densities of 2.66 and 1.01 spines/microns, respectively,
      uncorrected for so-called hidden spines. Bifurcating spines made up 2.1% of the
      total spine number in transversely and 2.3% in longitudinally sectioned
      dendrites. The twin spine heads never shared the same presynaptic bouton.
      Fenestrated or split PSDs shared the same presynaptic element in all but two
      cases, arguing against PSD division as an intermediate step in synapse formation.

PMID- 8986870
TI  - Secretoneurin: a market in rat hippocampal pathways.
AB  - Secretoneurin is a 33-amino acid peptide, generated in brain by proteolytic
      processing of secretogranin II. The distribution of secretoneurin-like
      immunoreactivity and secretogranin II mRNA was investigated in the hippocampus of
      the rat. Secretogranin II mRNA was found in high concentrations throughout the
      granule cell and pyramidal cell layers and in many local neurons, notably in the
      hilus of the dentate gyrus. The general distributional pattern of secretoneurin
      like immunoreactivity was characterized by a prominent staining in the area of
      the terminal field of mossy fibers with an obvious staining in the infrapyramidal
      area of CA3 and a strongly immunopositive band in the inner third of the
      molecular layer of the dentate gyrus. Lesions of the granule cells by local
      injection of colchicine significantly reduced secretoneurin-like immunoreactivity
      in the terminal field of mossy fibers, but not in the inner molecular layer of
      the dentate gyrus. On the other hand, destruction of interneurons of the dentate
      gyrus (mossy cells and certain gamma-aminobutyricacid-ergic interneurons) by
      kainic acid-induced seizures was associated with a reduction of secretoneurin
      like immunoreactivity in the inner molecular layer of the dentate gyrus. However,
      30 days after kainic acid-induced seizures, a strongly secretoneurin
      immunoreactive band reappeared in this area, which at this late time point is due
      to sprouting of mossy fibers collaterals. Our experiments suggest a widespread
      distribution of secretoneurin-like immunoreactivity in neurons of the hippocampal
      formation with a preferential localization in excitatory pathways including
      associational/commissural fibers originating from secretoneurin-containing mossy
      cells.

PMID- 8986871
TI  - Immunocytochemical evidence for the involvement of an FMRFamide-related peptide
      in egg production in the flatworm parasite Polystoma nearcticum.
AB  - The monogenean flatworm Polystoma nearcticum exhibits reproductive synchrony with
      its treefrog host, Hyla versicolor, and becomes reproductively active only during
      the short period of host sexual activity at spawning. In this way, it provides a
      useful model system for exploring factors that may influence egg production in
      flatworm parasites. One such factor is the peptidergic innervation of the egg
      chamber or ootype. By using immunocytochemical techniques, the occurrence and
      distribution of GYIRFamide-like immunoreactivity, an authentic flatworm FMRFamide
      related peptide (FaRP), have been monitored in the cells and fibres innervating
      the reproductive apparatus of worms collected at different stages of host sexual
      activity. Serotonin (5-HT) immunoreactivity in the worm was mapped for
      comparison. Extensive immunostaining for the FaRP and 5-HT was obtained
      throughout both the central and the peripheral nervous systems of worms, which
      were recovered from reproductively active frogs. In contrast, the innervation of
      the ootype of worms that were determined to be sexually inactive, including those
      recovered from frogs postspawning, showed little or no immunoreactivity for the
      FaRP; immunostaining for 5-HT in the ootype was unaffected by the reproductive
      state of the worm. These results indicate that FaRP expression in the neurons of
      the ootype innervation of P. nearcticum coincides with the parasite's brief
      period of egg production and, thus, provides evidence that regulatory peptides
      may be involved in the egg-assembly mechanism in flatworm parasites.

PMID- 8986872
TI  - Distribution of nitric oxide synthase in rat dorsal vagal complex and effects of
      microinjection of nitric oxide compounds upon gastric motor function.
AB  - Nitric oxide (NO) has received attention as a vagal nonadrenergic-noncholinergic
      (NANC) mediator of gastrointestinal relaxation. The dorsal vagal complex (DVC) is
      the primary hindbrain site of vagal control of the gastrointestinal tract, and
      yet the subnuclear distribution of NO and its physiological effects have not been
      analyzed in this nucleus. Therefore, this study estimates the relative number of
      NO synthase (NOS)-containing neurons in subnuclear regions of the DVC, identifies
      NOS-containing vagal abdominal preganglionic neurons in the dorsal motor nucleus
      of the vagus, and defines a role of NO in the DVC in control of gastric motor
      function. The location of NADPH-diaphorase-positive staining (a marker of NOS
      activity) and NOS immunoreactivity overlap in the DVC. In the dorsal motor
      nucleus of the vagus there are positively stained cells caudal to the obex and at
      its most rostral extent, but not at the intermediate level. Intraperitoneal
      fluorogold combined with NADPH-diaphorase activity labels approximately 5% and
      15% of fluorogold-immunoreactive cells in the caudal and rostral dorsal motor
      nucleus of the vagus, respectively. Thus, a portion of NOS-containing neurons are
      preganglionic vagal neurons projecting to the abdominal viscera. In the nucleus
      tractus solitarius, the majority of NADPH-diaphorase-positive cells are within
      the centralis, medial, and ventral/ventrolateral subnuclei. Fiber/terminal
      staining is present in the subnucleus centralis, subnucleus gelatinosus,
      subpostremal zone, and the medial nucleus tractus solitarius. The presence of NOS
      terminal staining implicates NO in afferent control of gastric function in the
      DVC (e.g., vago-vagal circuits in subnucleus gelatinosus). To determine a role of
      NO in the DVC, NO-related agents were microinjected into the DVC in alpha
      chloralose-anesthetized rats while recording indices of gastric motor function. L
      Arginine, microinjected into the DVC, significantly decreases intragastric
      pressure (-2.2 +/- 0.4 cm2, N = 12), and this effect is abolished by vagotomy.
      Microinjection of an NOS inhibitor, NG-nitro-L-arginine methyl ester, increases
      intragastric pressure (1.9 +/- 0.7 cm2, N = 10), with the greatest effect in the
      DVC rostral to the obex. Overall, it was concluded that tonic release of NO in
      the DVC mediates gastric relaxation, at least in anesthetized animals, and NOS
      containing preganglionic neurons in the dorsal motor nucleus of the vagus may be
      "command" NANC neurons which control a variety of gastrointestinal functions.

PMID- 8986873
TI  - Development of microglia in the prenatal rat hippocampus.
AB  - The distribution and appearance of microglia cell precursors in the prenatal
      hippocampus were examined in embryonic day 14 (E14) to E21 rats by nucleoside
      diphosphatase histochemistry. For comparison, the differentiation of astroglial
      cells was analyzed from E17 by vimentin and glial fibrillary acidic protein
      immunohistochemistry. Based on morphologic features, nucleoside diphosphatase
      positive microglial cell precursors were classified as ameboid microglial cells
      and primitive ramified microglial cells. Ameboid microglia were present in the
      hippocampal primordium on E14. As the hippocampus developed, however, ameboid
      microglia gradually transformed into primitive ramified microglia, first
      recognized at E19. Microglial cell precursors, often related to nucleoside
      diphosphatase-labeled blood vessels, were particularly observed next to the pial
      surface on days E14 and E17 and in the highly vascularized area around the
      hippocampal fissure from E19. Within the brain parenchyma, the microglial cell
      precursors tended to be located within the differentiating cell and neuropil
      layers rather than in the germinative zones. The late developing dentate gyrus
      remained almost devoid of microglial cell precursors before birth. Vimentin
      positive astroglial processes with radial orientation were observed throughout
      the hippocampal subregions from E17. In contrast, glial fibrillary acidic protein
      positive, radial processes were barely discernible in the fimbria and the dentate
      gyrus before E19. The results are discussed in relation to the possible
      interactive role of microglial cells in central nervous tissue development and
      histogenesis. Regarding the origin of hippocampal microglial cell precursors, the
      present observations support the view that these cells may well originate from
      different mesodermal sources depending on time and localization.

PMID- 8986874
TI  - Morphology of globus pallidus neurons: its correlation with electrophysiology in
      guinea pig brain slices.
AB  - Intracellular recordings obtained from globus pallidus neurons in guinea pig
      revealed, on the basis of their membrane properties, the existence of at least
      two major (types I and II) and one minor (type III) groups of neurons. Type I
      neurons were silent at the resting membrane level and generated a burst of spikes
      with strong accommodation to depolarizing current injection. Type II neurons
      fired at the resting membrane level or with small membrane depolarization, and
      their repetitive firing (< or = 200 Hz) was very sensitive to the amplitude of
      injected current and showed weak accommodation. Type III neurons did not fire
      spontaneously at the resting membrane level. The neurons were morphologically
      characterized by intracellular injection of biocytin following the
      electrophysiological recordings. Among the major groups, the soma size of type I
      neurons (40 x 23 microns) was larger than that of type II neurons (29 x 17
      microns). Both types of neurons had three to six primary dendrites. Dendritic
      spines were very sparse. Occasionally, dendrites exhibited varicosities,
      especially in their terminal branches. Dendritic fields were disc-like in shape
      and were perpendicular to striopallidal fibers. Most of the axons had
      intranuclear collaterals. Main axonal branches projected rostrally or caudally,
      and in some neurons one axonal branch could be followed caudally, and another
      rostrally, into the striatum. These two types were major neurons in the globus
      pallidus and were considered to be projection neurons. Type III neurons were
      small (18 x 12 microns), and their dendrites were covered with numerous spines.
      They were considered to be interneurons.

PMID- 8986875
TI  - Projections of the marginal nuclei in the spinal cord of the pigeon.
AB  - In the avian spinal cord, there are several groups of neurons lying outside the
      central gray substance. The most conspicuous ones lie at the very margin of the
      ventrolateral cord. In the lumbosacral spinal cord, these marginal nuclei
      protrude into the vertebral canal to form accessory lobes. The projections of
      these marginal nuclei were studied in the pigeon by neuroanatomical tracing
      methods. Anterograde transport of tracer injected into the lumbosacral accessory
      lobes showed that these neurons project to the contralateral medial ventral gray
      and to paragriseal cells located in the contralateral ventral and lateral white
      matter of lumbosacral segments. Double-labeling experiments disclosed that
      lumbosacral paragriseal cells projecting to the cerebellum are contacted by
      accessory lobe axon terminals. The projection of cervical marginal nuclei was
      studied with retrograde transport of tracers applied to the spinal tracts in the
      lateral funiculus. Retrogradely labeled cells were found in contralateral
      marginal nuclei of both rostral and caudal segments. All marginal nuclei have an
      ascending and a descending projection spanning about five segments each. The
      possible role of marginal nuclei in sensorimotor circuits is discussed.

PMID- 8986876
TI  - Optic nerve regenerates but does not restore topographic projections in the
      lizard Ctenophorus ornatus.
AB  - In adult fish and amphibians, the severed optic nerve regenerates and visual
      behaviour is restored. By contrast, optic axons do not regenerate in the more
      recently evolved birds and mammals. Here we have investigated optic nerve
      regeneration in a member of the class Reptilia, phylogenetically intermediate
      between the fish and amphibians and the birds and mammals. We assessed visual
      recovery anatomically and behaviourally one year after unilateral optic nerve
      crush in the adult ornate dragon lizard. Ctenophorus ornatus. Ganglion cell
      densities and numbers of axons in the optic nerve on either side of the crush
      site indicated that two-thirds of ganglion cells survived axotomy and regrew
      their axons. However, myelination fell from a mean of 21% in normals to 5.5% and
      3%, proximal and distal to the crush, respectively. Anterograde labelling of the
      entire optic nerve showed that axons regenerated along essentially normal
      pathways and that the major projection, as in normals, was to the superficial one
      third of the contralateral optic tectum. However, localised retinal injections
      indicated that regenerated projections lacked retinotopic order. Any one retinal
      region projected to the entire tectum. This feature presumably explains why the
      experimental lizards consistently appeared blind to stimuli via the regenerated
      nerve. Our findings indicate that although axons regenerate along essentially
      normal pathways in adult lizards, conditions within the visual centres do not
      allow regenerating optic axons to select appropriate central connections. In a
      wider context, the result suggests that the ability for regenerating central
      axons to form topographic maps may also have been lost in the more recently
      evolved vertebrate classes.

PMID- 8986877
TI  - Distribution of NADPH-diaphorase and nitric oxide synthase in relation to
      catecholaminergic neuronal structures in the brain of the lizard Gekko gecko.
AB  - A recent study of the distribution of NADPH-diaphorase (NADPHd) and nitric oxide
      synthase (NOS) in a turtle brain (Bruning et at. [1994]: J. Comp. Neurol. 348:183
      206) has revealed that these enzymes are not only widely distributed throughout
      the brain, but also seem to be colocalized with other classical
      neurotransmitters, such as catecholamines and acetylcholine. The main goals of
      the present study were 1) to determine sites of colocalization of NADPHd/NOS with
      tyrosine hydroxylase (TH, as marker for catecholamines), and 2) by studying a
      representative of another reptilian radiation, to assess primitive and derived
      traits of the distribution of NADPHd and NOS in the brains of reptiles. For that
      purpose, single (NADPHd or NOS) and double staining (NADPHd with TH, or NOS with
      TH) techniques were applied to the brains of adult gekkonid lizards (Gekko
      gecko). The distribution of NADPHd and NOS in Gekko was largely comparable to
      that in turtles, which implies involvement in certain functions of these enzymes.
      Notable differences, however, were observed in the thalamus and pretectum.
      Colocalization was observed in numerous cells of the ventral tegmental area, the
      substantia nigra, and the retrorubral dopaminergic cell group. In other
      catecholaminergic cell groups, e.g., the locus coeruleus and the solitary tract
      nucleus, TH-immunoreactive cells and NADPHd/NOS-positive cells were closely
      intermingled, but not double-stained. From the present evidence, it is concluded
      that extensive colocalization of NADPHd/NOS with catecholamines occurs in the
      midbrain dopaminergic cell groups of reptiles and birds, but not (or only
      sparsely) in the corresponding cell groups of amphibians and mammals.

PMID- 8986878
TI  - Distribution of GABA, glycine, and glutamate immunoreactivities in the vestibular
      nuclear complex of the frog.
AB  - This study describes the localization of gamma-aminobutyric acid (GABA), glycine,
      and glutamate immunoreactive neurons, fibers, and terminal-like structures in the
      vestibular nuclear complex (VNC) of the frog by using a postembedding procedure
      with consecutive semithin sections at the light microscopic level. For purposes
      of this study, the VNC was divided into a medial and lateral region.
      Immunoreactive cells were observed in all parts of the VNC. GABA-positive
      neurons, generally small in size, were predominantly located in the medial part
      of the VNC. Glycine-positive cells, more heterogeneous in size than GABA-positive
      cells, were scattered throughout the VNC. A quantitative analysis of the spatial
      distribution of GABA glycine immunoreactive cells revealed a complementary
      relation between the density of GABA and glycine immunoreactive neurons along the
      rostrocaudal extent of the VNC. In about 10% of the immunolabeled neurons, GABA
      and glycine were colocalized. Almost all vestibular neurons were, to a variable
      degree, glutamate immunoreactive, and colocalization of glutamate with GABA
      and/or glycine was typical. GABA, glycine, or glutamate immunoreactive puncta
      were found in close contact to somata and main dendrites of vestibular neurons. A
      quantitative analysis revealed a predominance of glutamate-positive terminal-like
      structures compared to glycine or GABA containing profiles. A small proportion of
      terminal-like structures expressed colocalization of GABA and glycine or glycine
      and glutamate. The results are compared with data from mammals and discussed in
      relation to vestibuloocular and vestibulo-spinal projection neurons, and
      vestibular interneurons. GABA and glycine are the major inhibitory transmitters
      of these neurons in frogs as well as in mammals. The differential distribution of
      GABA and glycine might reflect a compartmentalization of neurons that is
      preserved to some extent from the early embryogenetic segmentation of the
      hindbrain.

PMID- 8986879
TI  - Organisation of the reticular thalamic projection to the intralaminar and midline
      nuclei in rats.
AB  - This study examines the projection of the reticular thalamic nucleus to the
      classic "nonspecific" dorsal thalamic nuclei of rats. Individual nuclei of the
      intralaminar (central-lateral, paracentral, central-medial, parafascicular) and
      the midline (reuniens/rhomboid, parataenial) nuclear groups, together with the
      reticular nucleus itself, were injected with the neuronal tracers biotinylated
      dextran or fluorescent latex microspheres (red or green). Reticular cells
      projecting to the intralaminar and midline nuclei are limited largely to the
      rostral pole of the nucleus. Within the rostral pole, most reticular cells
      projecting to the intralaminar and midline nuclear groups are found in largely
      distinct sectors; cells that project to the intralaminar nuclei tend to lie more
      laterally, whereas those projecting to the midline nuclei lie more medially
      within the pole. Among the individual nuclei of both the intralaminar and midline
      nuclear groups, however, the segregation is far less distinct. For instance, the
      reticular cells that project to the intralaminar central-lateral, central-medial,
      paracentral, and parafascicular nuclei are intermixed completely on the lateral
      edge of the rostral pole. After separate injections of different colored latex
      microspheres into individual intralaminar nuclei, the incidence of double
      labelled reticular cells is about 37%, a percentage much higher than among the
      "specific" dorsal thalamic nuclei (< 1%). All the above-mentioned results refer
      to the reticular labelling seen on the side ipsilateral to the injection. After
      separate injections into the intralaminar central-medial nucleus, the midline
      nuclei, and the reticular nucleus itself, we also see a very small group of
      reticular cells labelled on the contralateral side. In general, our results
      indicate that the reticular projection to the intralaminar and midline nuclei is
      far more diffuse than the reticular projection to the specific dorsal thalamic
      nuclei.

PMID- 8986880
TI  - Vocal control pathways through the anterior forebrain of a parrot (Melopsittacus
      undulatus).
AB  - A feature of the telencephalic vocal control system in the budgerigar
      (Melopsittacus undulatus) that has been hypothesized to represent a profound
      difference in organization from the oscine vocal system is its reported lack of
      an inherent circuit through the anterior forebrain. The present study reports
      anatomical connections that indicate the existence of an anterior forebrain
      circuit comparable in important ways to the "recursive" pathway of oscine
      songbirds. Results from anterograde and retrograde tracing experiments with
      biocytin and fluorescently labeled dextran amines indicate that the central
      nucleus of the anterior archistriatum (AAc) is the source of ascending
      projections upon the oval nuclei of the anterior neostriatum and ventral
      hyperstriatum (NAo and HVo, respectively). Efferent projections from the latter
      nuclei terminate in the lateral neostriatum afferent to AAc, thereby forming a
      short recurrent pathway through the pallium. Previously reported projections from
      HVo and NAo upon the magnocellular nucleus of the lobus parolfactorius (LPOm),
      and after LPOm onto the magnocellular nucleus of the dorsal thalamus (DMm; G.F.
      Striedter [1994] J. Comp. Neurol. 343:35-56), are confirmed. A specific
      projection from DMm onto NAom is also demonstrated; therefore, a recurrent
      pathway through the basal forebrain also exists in the budgerigar vocal system
      that is similar to the anterior forebrain circuit of oscine songbirds. Parallels
      between these circuits and mammalian basal ganglia-thalamo-cortical circuits are
      discussed. It is hypothesized that vocal control nuclei of the avian anterior
      neostriatum may perform a function similar to the primate supplemental motor
      area.

PMID- 8986881
TI  - Developmentally regulated expression of calcitonin gene-related peptide in the
      superior olive.
AB  - During postnatal development, the expression of calcitonin gene-related peptide
      (CGRP) and its mRNA was investigated in the superior olivary complex of the
      hamster in order to better understand its role in the development of the efferent
      olivocochlear (OC) pathway. Although both the peptide and its mRNA were expressed
      at birth in a few periolivary cells, neither CGRP mRNA nor any immunoreactivity
      could be detected in the lateral superior olive until after postnatal day (P) 5.
      By P9, CGRP expression had significantly increased and was mostly contained
      within the lateral superior olive. Between P7 and P18, there appears to be a
      transient increase in the transcript expression both in periolivary regions and
      in the lateral superior olive. Notably, both peptide and mRNA expression
      decreased precipitously throughout the superior olive after P18. In comparison,
      although both the facial and trigeminal motor nuclei had significant CGRP
      expression at birth, the facial motor nucleus demonstrated a decrease in the
      level of CGRP expression between P1 and P6, while the trigeminal motor nucleus
      reached a maximal level of expression around P18. If CGRP expression is related
      to synaptogenesis in OC neurons, as has been suggested for certain motor neurons,
      then we predict that the ephemeral increases in transcript expression in OC
      neurons are related to synaptogenetic mechanisms in the cochlear periphery.
      Importantly, the time course for CGRP expression in lateral OC neurons indicates
      that their OC terminals in the cochlear periphery may not begin forming synapses
      until near the end of the 1st postnatal week.

PMID- 8986882
TI  - Calretinin in the thalamic reticular nucleus of the rat: distribution and
      relationship with ipsilateral and contralateral efferents.
AB  - In order to investigate the existence of anatomical subdivisions within the
      thalamic reticular nucleus (Rt), the distribution of reticular neurons expressing
      the calcium binding protein calretinin was investigated in the rat by means of
      immunocytochemistry. Calretinin immunoreactive (Cr-ir) neurons were mainly
      distributed in the lateral and ventral regions, and along the medial border of
      the Rt rostral pole. Caudal to the rostral pole, many neurons were Cr-ir in the
      more dorsal part of the rostral two-thirds (the "dorsal cap") of the Rt. Fewer Cr
      ir neurons were present more caudally along the lateral and medial borders, and
      in the caudalmost part of the nucleus, related to the acoustic thalamus. The
      distribution of Cr-ir neurons in the rostral Rt was compared with that of neurons
      projecting to the ipsilateral and contralateral anterior, intralaminar, midline,
      and mediodorsal nuclei, or to the contralateral rostral Rt. The retrograde
      transport of Fluorogold revealed a remarkably precise topography of the rostral
      Rt: different reticular areas were found to project to different thalamic nuclei,
      or to different rostrocaudal or mediolateral portions of the same thalamic
      nucleus, with a limited degree of overlap. The double-labeling experiments
      demonstrated that the reticular neurons projecting to the ipsilateral
      anterodorsal, midline, mediodorsal, and anterior intralaminar nuclei frequently
      expressed calretinin; by contrast, the majority of the reticular commissural
      neurons did not express the protein, with the exception of neurons projecting to
      the contralateral mediodorsal and midline nuclei. The ipsilaterally projecting
      calretinin-positive neurons were frequently located along the medial edge of the
      rostral pole and in the dorsal cap of the nucleus, segregated from the
      commissural calretinin-negative neurons. The combined analysis of calretinin
      expression patterns and tract tracing data provided further insight in the
      anatomical organization of the thalamic reticular nucleus, suggesting a different
      neurophysiological role for the ipsilaterally vs. the contralaterally projecting
      reticular neurons in the modulation of the synaptic activity of the dorsal
      thalamus.

PMID- 8986883
TI  - Multi-segmental innervation of single pontine reticulospinal axons in the cervico
      thoracic region of the cat: anterograde PHA-L tracing study.
AB  - To characterize the fine morphology of individual reticulospinal axons at
      multiple spinal segments, localized injections of the anterograde neural tracer,
      Phaseolus vulgaris leucoagglutinin (PHA-L), were made into the nucleus
      reticularis pontis oralis (NRPo) of the cat. Following survival periods of 6-8
      weeks, labelled axons, between 1 and 8 microns in diameter, were found throughout
      the cervical and upper thoracic segments. Thick axons (diameter > or = 3 microns)
      were found to descend beyond the upper thoracic spinal cord, while most thin
      axons (diameter < 3 microns) ended in the upper cervical cord. From serial
      transverse sections (50 microns) of segments C3 to T2, in four cats, the
      trajectories of 23 single, thick reticulospinal axons were traced in continuity
      over distances of between 21.8 and 59.4 mm, corresponding to 3 and 8 segments,
      respectively. Most axons gave off at least one, and as many as four collaterals
      per segment, some preferentially in the cervical enlargement. The remainder gave
      off collaterals at most but not all segments. Detailed reconstruction of the
      collateralization and arborization in the spinal gray matter showed two major
      termination types, one where terminals remained ipsilateral to the stem axon, the
      other where additional collaterals extended across the midline from the
      ipsilateral gray matter to terminate in the contralateral gray matter. Axons
      tended to have collaterals of one type or the other, irrespective of the
      rostrocaudal level. Both ipsilateral and bilateral projections terminated mainly
      in laminae VII or VIII although the branching patterns varied from axon to axon.
      Individual stem axons, in general, showed similar termination patterns at each
      level.

PMID- 8986884
TI  - Projections from the cervical enlargement to the cerebellar nuclei in the rat,
      studied by anterograde axonal tracing.
AB  - Spinocerebellar projections from the cervical enlargement originate from neurons
      in the medial part of lamina VI and the central part of lamina VII. In the
      present study, the topographic projections of the cervical enlargement to the
      cerebellar nuclei were examined by anterograde tracing with biotinylated dextran
      in the rat. Following injections of the tracer into the spinal cord at levels
      between the C5 and T1 segments, anterogradely labeled axons and terminals were
      immunohistochemically demonstrated in the cerebellar nuclei. Unilateral
      injections revealed that projections are bilateral, but predominantly
      ipsilateral, to the cells of origin. Labeled axons entered the media nucleus from
      its rostrodorsal and rostromedial aspects. Labeled terminals were distributed to
      dorsal and medial parts of the middle subdivision at its rostral levels and to
      medial parts of the caudomedial subdivision of the medial nucleus. Most axons
      terminated in the middle subdivision. Single axons were seen to course
      rostrocaudally in the medial nucleus and give off terminal axons to both
      subdivisions. A few labeled terminals were seen in the dorsolateral protuberance
      of the medial nucleus, and in the anterior interpositus and the posterior
      interpositus nuclei. No labeled terminals were seen in the lateral cerebellar
      nucleus. The present study demonstrates that spinocerebellar neurons in laminae
      VI and VII of the cervical enlargement project to dorsomedial areas of the medial
      nucleus at rostral levels, bilaterally but predominantly ipsilaterally. It is
      suggested that these areas specifically receive cutaneous and muscular input
      related to the forelimb movement.

PMID- 8986885
TI  - Primary sensory and forebrain motor systems in the newborn brain are
      preferentially damaged by hypoxia-ischemia.
AB  - Cerebral hypoxia-ischemia causes encephalopathy and neurologic disabilities in
      newborns by unclear mechanisms. We tested the hypothesis that hypoxia-ischemia
      causes brain damage in newborns that is system-preferential and related to
      regional oxidative metabolism. One-week-old piglets were subjected to 30 minutes
      of hypoxia and then seven minutes of airway occlusion, producing asphyxic cardiac
      arrest, followed by cardiopulmonary resuscitation and four-day recovery. Brain
      injury in hypoxic-ischemia piglets (n = 6) compared to controls (n = 5) was
      analyzed by hematoxylin-eosin, Nissl, and silver staining, relationships between
      regional vulnerability and oxidative metabolism were evaluated by cytochrome
      oxidase histochemistry. Profile counting-based estimates showed that 13% and 27%
      of neurons in layers II/III and layers of somatosensory cortex had ischemic
      cytopathology, respectively; CA1 neuronal perikarya appeared undamaged, and < 10%
      of CA3 and CA4 neurons were injured; and neuronal damage was 79% in putamen, 17%
      in caudate, but nucleus accumbens was undamaged. Injury was found preferentially
      in primary sensory neocortices (particularly somatosensory cortex), basal ganglia
      (predominantly putamen, subthalamic nucleus, and substantia nigra reticulata),
      ventral thalamus, geniculate nuclei, and tectal nuclei. In sham piglets,
      vulnerable region generally had higher cytochrome oxidase levels than less
      vulnerable areas. Postischemic alterations in cytochrome oxidase were regional
      and laminar, with reductions (31-66%) occurring in vulnerable regions and
      increases (20%) in less vulnerable areas. We conclude that neonatal hypoxia
      ischemia causes highly organized, system-preferential and topographic
      encephalopathy, targeting regions that function in sensorimotor integration and
      movement control. This distribution of neonatal encephalopathy is dictated
      possibly by regional function, mitochondrial activity, and connectivity.

PMID- 8986886
TI  - Molecular characterization of E587 antigen: an axonal recognition molecule
      expressed in the goldfish central nervous system.
AB  - The E587 antigen (Ag) is a 200-Kd membrane glycoprotein originally identified by
      a monoclonal antibody on new and regenerating retinal ganglion cell axons in the
      adult goldfish. We report the isolation of cDNAs encoding the E587 Ag and
      identify it as a member of the L1 family of cell adhesion molecules (CAMs). The
      predicted amino acid sequence of E587 Ag shows an approximately equal identity
      (40%) to mouse L1, chick neuron-glia CAM, and chick neuron-glia-related CAM.
      Although the overall similarity is low, there is a high conservation of
      structural domains and specific sequence motifs. Wholemount in situ
      hybridizations were performed on goldfish between 34 hours and 3 days
      postfertilization (pf). A dramatic increase in E587 Ag mRNA was observed between
      34 and 48 hours pf. The expression of E587 Ag mRNA in neurons shortly precedes
      axonogenesis. A marked decrease in expression occurs by 3 days pf, when the
      axonal scaffold has already been established. Wholemount immunohistochemistry on
      embryos demonstrates expression of E587 Ag on all major tracts. E587 Ag is absent
      from mature retinal ganglion cell axons, but its expression is induced by optic
      nerve transection. A corresponding induction of E587 Ag mRNA in retinal ganglion
      cells is shown by in situ hybridization. Furthermore, E587 Ag mRNA was detected
      in the optic nerve, which suggests that nonneuronal cells also express this
      molecule. E587 Ag was previously shown to promote retinal axon fasciculation and
      outgrowth in young fish and to mediate axon-glial interactions in vitro. The
      expression pattern and developmental regulation of E587 Ag in the central nervous
      system, its reexpression in retinal ganglion cells following optic nerve
      transection, and its relation to the L1 family indicate that E587 Ag functions as
      a cell recognition molecule important during axonal growth and regeneration.

PMID- 8986887
TI  - Distribution of motoneurons supplying feline neck muscles taking origin from the
      shoulder girdle.
AB  - A combination of fluorescent retrograde tracers and horseradish peroxidase (HRP)
      was used to compare the spinal distributions of motoneurons supplying shoulder
      muscles with attachments to the skull and cervical spinal cord that suggest a
      significant role in head movement. Two muscles, the rhomboideus and the levator
      scapulae, were innervated by multiple segmental nerve bundles that entered the
      muscles at different rostrocaudal locations. Motoneurons that were labelled
      retrogradely from rhomboideus nerve bundles formed a single, long column in the
      ventral horn from C4 to C6, lateral to previously studied motor nuclei supplying
      deep neck muscles. When different tracers were used to differentiate motoneurons
      supplying specific nerve bundles, discrete subnuclei could be identified that
      were organized in a rostrocaudal sequence corresponding to the rostrocaudal order
      of the nerve bundles. Levator scapulae motoneurons formed a second elongate
      column immediately lateral to the rhomboidues motor nucleus. Three other muscles,
      that trapezius, sternomastoideus, and cleidomastoideus, were supplied by cranial
      nerve XI. Labelled motoneurons from these muscles formed a single column from the
      spinomedullary junction to middle C6. Within this column, the three motor nuclei
      supplying the sternomastoideus, cleidomastoideus, and trapezius were laminated
      mediolaterally. Sternomastoideus and cleidomastoideus motoneurons were confined
      to upper cervical segments, whereas trapezius motoneurons were found from C1 to
      C6. In C1 and C6, the motoneuron column was located centrally in the gray matter,
      but, between C2 and C5, the column lay on the lateral wall of the ventral horn in
      a position dorsolateral to motor nuclei supplying the rhomboideus and the deeper
      neck muscles. The findings in this study suggest that descending and
      propriospinal systems responsible for coordinating head movement may have to
      descend as far caudally as C6 if they are to project onto muscles controlling the
      mobility of the lower neck.

PMID- 8986888
TI  - Lateral ankle instability and the Brostrom-Gould procedure.
AB  - Lateral ankle instability can present as either acute or chronic. Proper
      identification of the etiology is necessary to determine the proper treatment
      plan. The Brostrom-Gould procedure, when properly used, can provide adequate
      correction of the unstable ankle. A review of the procedure, its indications, and
      the results of 44 patients who underwent the procedure will be discussed.

PMID- 8986889
TI  - Salvage of first metatarsophalangeal joint by creation of artificial extensor
      hood apparatus.
AB  - The purpose of this procedure was to salvage a first metatarsophalangeal joint
      after extensor hallucis longus tendon rupture, repair, re-rupture, and severe
      scarring in a 23-year-old female patient who originally underwent a bunionectomy
      and extensor hallucis longus tendon lengthening surgery. Initially, the existing
      functional tendon was surgically identified and freed from surrounding scar
      tissue, which provided only partial improvement. After this surgery, the patient
      exhibited only 30 degrees of active dorsiflexion of the first metatarsophalangeal
      joint with pain. To re-establish normal function, an artificial extensor hood
      apparatus (sling portion only) was later implanted into the first metatarsal head
      to augment function of the dorsiflexory power of the extensor hallucis longus.
      After reconstruction and implantation of an artificial extensor hood apparatus,
      the first metatarsophalangeal joint and extensor hallucis longus tendon have
      returned to normal function.

PMID- 8986890
TI  - Classification of diabetic foot wounds.
AB  - Foot ulcers in persons with diabetes are one of the most common precursors to
      lower extremity amputation. Appropriate care of the diabetic foot ulceration
      requires a clear, descriptive classification system that may be used to direct
      appropriate therapy and possibly predict outcome. Ideally, this system would be
      used by all participants in a multidisciplinary limb salvage team. We describe a
      clinical classification system for diabetic foot wounds that evaluates wound
      depth, the presence of infection, and peripheral arterial occlusive disease in
      every category of the wound assessment. The goal of this system is to improve
      communication, leading to a less complex, more predictable treatment course and,
      ultimately, an improved result.

PMID- 8986891
TI  - Chevron bunionectomy with microplate and screw fixation: a retrospective follow
      up of 26 feet.
AB  - The authors report the results of 21 patients (26 feet) who had Chevron osteotomy
      of the first metatarsal head to correct hallux valgus. Fixation was achieved by
      using a small plating system consisting of one L-plate (8.5 mm x 17 mm x 0.8 mm)
      and four screws (1.6 mm). Results showed no capital fragment displacement,
      avascular necrosis, or plate deformation. One case of screw loosening was noted
      on x-rays. This patient noted occasional irritation over the plate while wearing
      shoes. Symptoms did not cause the patient to seek removal of the plate and
      screws. The small plate system allows the surgeon to perform the osteotomy as
      originally described by Austin, with the added security of rigid internal
      fixation.

PMID- 8986893
TI  - Economic outcomes analysis from an ambulatory surgical center.
AB  - In the competitive healthcare marketplace, foot surgeons are being placed under
      pressure to demonstrate the economic value of surgical care. The management
      methodology of "fiscal outcomes review" is one tool being used to evaluate such
      care. Initially developed for internal corporate management as an executive
      decision support system, the process is being used an an external cost control
      technique to "economically credential" providers of surgical care. Consequently,
      the economic outcomes analysis of a single surgical procedure represents a first
      attempt to gather, allocate, analyze, and interpret meaningful charge information
      relative to the podiatric Ambulatory Surgery Center setting. When compared with
      the traditional outpatient hospital setting, charge reductions are documented
      without compromising quality. The long-held belief that Ambulatory Surgery Center
      surgery is more efficient than traditional outpatient surgery, can then be
      corroborated.

PMID- 8986892
TI  - Accessory soleus muscle: a review of the literature and case report.
AB  - The accessory soleus is a rare anatomic variant that must be considered in the
      differential diagnosis of all posteromedial soft tissue masses of the ankle. The
      authors review and discuss the pertinent findings of the previously reported 70
      cases of accessory soleus muscles cited in English literature. A case report is
      presented that highlights the diagnosis of the accessory soleus muscle with
      magnetic resonance imaging studies and surgical excision of the mass in a
      symptomatic patient.

PMID- 8986894
TI  - Asymmetric "V" osteotomy: a predictable surgical approach for chronic central
      metatarsalgia.
AB  - Chronic metatarsalgia is a condition found through the years to present many
      treatment difficulties. These difficulties began with a lack of understanding,
      not only concerning the etiologic nature of this condition, but failure to
      appreciate the surgical treatment ramifications inherent to alterations in the
      metatarsal parabola. These failures have subsequently led to lesions under the
      adjacent metatarsal heads, stress fractures, flail toes, and other postoperative
      pathology. This often leads to further surgical intervention or accommodative
      modifications. The authors offer an analysis of surgical approaches to this
      problem and present a more predictable surgical technique to enhance the
      metatarsal parabola, while decreasing either excessive plantarflexion of a
      particular metatarsal or set of metatarsals. To date the senior author (E.L.) has
      performed the asymmetric "V" osteotomy on 30 patients for a total of 40
      metatarsals. After a 12- to 18-month postoperative period, there have been no
      significant complications, including recurrences, transfer lesions, excessive
      secondary bone callous, malunions, or adjacent metatarsalgia. Delayed union with
      secondary bone callous has developed in two instances. The authors introduce an
      innovative surgical approach to structural metatarsal abnormalities as a distinct
      advantage to other previously described osteotomies with greater predictability,
      better anatomic reduction, primary bone healing, and faster return to normal
      activities.

PMID- 8986895
TI  - Major arthrodeses in patients with neuropathic arthropathy.
AB  - Neuropathic arthropathy is a complex deformity found in a multitude of disease
      processes. Various forms of conservative and surgical treatment options have been
      reported throughout the literature; however, a limited number of such treatments
      address the underlying deformity. This article reviews the indications and
      surgical criteria necessary to perform successful arthrodesis procedures in
      patients afflicted with this problem. A case report is presented, using
      arthrodesis as a salvage procedure for a painful Charcot deformity of the midfoot
      in a patient with diabetic neuroarthropathy.

PMID- 8986896
TI  - Lateral calcaneal artery flap for coverage of a posterior heel defect in a child.
AB  - The lateral calcaneal artery fasciocutaneous transpositional flap is utilized for
      coverage in a case presentation of a 6-year-old child with an insensate posterior
      heel defect. The procedural technique and 32-month follow-up is described.
      Advocacy of this flap, for this patient, and potential detriments of alternative
      coverage options are discussed.

PMID- 8986897
TI  - Recurrent plantar ulceration following pan metatarsal head resection.
AB  - Although the pan metatarsal head resection, since it was originally described and
      performed by Hoffman in 1911, has proven to be an effective and viable procedure
      in treating many forefoot deformities, it is not without its own complications.
      The authors provide an historical perspective of the pan metatarsal head
      resection, a discussion on the complication of recurrent plantar ulceration after
      the pan metatarsal head resection, and a review of their own experience with this
      procedure. A retrospective review was performed of all patients having undergone
      pan metatarsal resections between August 1980 and April 1993. Twenty procedures
      were performed on 12 patients with diabetic neuropathy, and 21 procedures were
      performed on 15 patients with rheumatoid arthritis. The incidence of recurrent
      plantar ulceration after surgical correction was 25% and 28%, respectively. All
      27 patients underwent primary healing. The authors, therefore, conclude that the
      complication of recurrent plantar ulceration after this procedure is a very
      likely and distinct possibility.

PMID- 8986898
TI  - Streptococcal toxic shock syndrome from a puncture wound to the foot.
AB  - Puncture wounds to the foot are a common occurrence. If treated properly, the
      majority will be resolved without major complications. Toxic shock syndrome and
      streptococcal toxic shock-like syndrome are devastating complications of some
      staphylococcal and streptococcal infections. This paper discusses the
      similarities and differences between the two toxic states, reviews the
      pathophysiology, and presents a case report of near-fatal streptococcal toxic
      shock-like syndrome secondary to a puncture wound of the foot.

PMID- 8986899
TI  - Is prophylactic diabetic foot surgery dangerous?
AB  - Any treatment rendered to the deformed, insensate foot should be undertaken with
      the prime intentions of reducing the potential for future limb-threatening events
      and allowing the patient to continue as an ambulatory, productive member of
      society. The purpose of this article is to compare morbidity and outcomes of
      elective foot surgery among diabetics and nondiabetics with isolated toe
      deformities. We compared the prevalence of infection, wound complication, and
      recurrence of ulcers in 31 diabetics and 33 nondiabetics. All of these patients
      received a single proximal interphalangeal joint arthroplasty with a mean follow
      up of 3 years (range 12 to 61 months). The diabetic group was divided into two
      subgroups: 1) insensate with deformity, but no history of ulceration, and 2)
      insensate with deformity and a previous history of ulceration. Diabetics with a
      history of ulceration were more likely to experience a postoperative infection
      (14.3%) than neuropathic diabetic patients with no history of ulceration (0%) and
      nondiabetic subjects (0%) (p = 0.04, Cl = 3.1 to 8.6). There was not a
      significant difference in prevalence of dehiscence among diabetic and nondiabetic
      groups (16.1% versus 9.1%, respectively, Cl = 0.4 to 8.8). The long-term outcomes
      after prophylactic surgery at a site of previous ulceration were uniformly good,
      with 96.3% of patients remaining ulcer-free a mean of 3 years postoperatively.

PMID- 8986900
TI  - Deep venous thrombosis and pulmonary embolism following cast immobilization of
      the lower extremity.
AB  - It is generally accepted that venous thrombosis in the lower extremity
      predisposes to pulmonary embolism. A case of pulmonary embolism after cast
      immobilization of the lower extremity, as well as a review of thromboembolic
      disease is presented. A high level of vigilance and close follow-up of even
      simple cast treatment is necessary to avoid this complication.

PMID- 8986901
TI  - Grand rounds: sports medicine.

PMID- 8986902
TI  - White-coat hypertension: misnomers, misconceptions and misunderstandings. What
      should we do next?

PMID- 8986903
TI  - Parathyroid hypertensive factor and intracellular calcium regulation.

PMID- 8986904
TI  - M235-->T polymorphism of the angiotensinogen gene predicts hypertension in the
      elderly.
AB  - OBJECTIVE: To determine whether the M235-->T polymorphism (exon 2) of the
      angiotensinogen gene is associated with hypertension in elderly patients with
      isolated systolic hypertension [ISH: systolic blood pressure (SBP) > or = 160
      mmHg, diastolic blood pressure (DBP) < 90 mmHg) or systolic-diastolic
      hypertension (SDH: DBP > or = 90 mmHg, SBP > or = 160 mmHg) compared with
      normotensive controls (SBP < 160 mmHg, DBP < 90 mmHg). DESIGN: A case-control
      study in 769 non-institutionalized, elderly (aged > or = 60 years; female:male
      ratio 0.85) residents of Dubbo, New South Wales. METHODS: Individuals were
      classified as having ISH (n = 171), having SDH (n = 218) and being normotensive
      controls (n = 366) with age and sex matching. MM, TT and MT genotypes were
      determined by a nested polymerase chain reaction strategy using DNA extracted
      from serum. The prediction of ISH or SDH by genotype or allele was examined in a
      multiple-logistic regression model that controlled for various confounders.
      RESULTS: SBP (mean +/- SD, mmHg)/DBP (mean +/- SD, mmHg) was 176 +/- 16/79 +/- 8
      in the ISH group, 167 +/- 23/97 +/- 7 in the SDH group and 134 +/- 14/74 +/- 9 in
      the normotensive control group. The frequencies of M and T alleles in the normal
      population (0.69 and 0.31, respectively) were altered significantly in the ISH
      group (0.61 and 0.39, respectively; chi 2 = 6.0, P < 0.02) and the SDH group
      (0.62 and 0.38, respectively; chi 2 = 6.0, P < 0.02). The presence of the TT
      genotype predicted both ISH (odds ratio 1.9, 95% confidence interval 1.1-3.3) and
      SDH (1.7, 1.0-3.0) as did that of the T allele (ISH: 1.3, 1.0-1.7; SDH: 1.3, 1.0
      1.7). CONCLUSIONS: The M235-->T polymorphism may be a marker for both forms of
      hypertension in the elderly. Whether the TT genotype represents a genetic risk
      factor for the development of hypertension in later life requires confirmation.

PMID- 8986905
TI  - Hepatocyte growth factor is a novel member of the endothelium-specific growth
      factors: additive stimulatory effect of hepatocyte growth factor with basic
      fibroblast growth factor but not with vascular endothelial growth factor.
AB  - OBJECTIVE: To seek an endothelium-specific growth factor by examining the
      mitogenic effects of hepatocyte growth factor (HGF) on endothelial cells and on
      vascular smooth muscle cells (VSMC). METHODS: Rat and human endothelial cells and
      VSMC were employed. DNA, RNA and protein synthesis were measured by using [3H]
      thymidine, uridine and leucine. Coculture of endothelial cells with VSMC was also
      performed to study the role of endothelial cells. RESULTS: Coculture of
      endothelial cells with VSMC resulted in a significant decrease in DNA synthesis
      of VSMC. HGF, as well as basic fibroblast growth factor (bFGF), stimulated DNA,
      RNA and protein synthesis by endothelial cells in a dose-dependent manner.
      Interestingly, co-incubation of endothelial cells with HGF and bFGF resulted in
      an additive stimulation of DNA synthesis. Similarly, HGF and interleukin-1 alpha
      and -6 stimulated DNA synthesis by coronary endothelial cells, whereas
      interleukin-1 beta and transforming growth factor-beta (TGF-beta) did not.
      However, HGF showed markedly different actions from bFGF on VSMC growth. bFGF,
      TGF-beta, interleukin-1 alpha, -1 beta and -6 stimulated DNA synthesis in VSMC
      significantly, whereas HGF did not. Finally, we examined the mitogenic effect of
      HGF on human aortic endothelial cells and VSMC. Incubation with HGF increased DNA
      synthesis and growth by endothelial cells in a dose-dependent manner, whose
      degree was significantly greater than those with bFGF, vascular endothelial
      growth factor (VEGF) and interleukin-6. Addition of HGF and VEGF showed no
      additive effect on DNA synthesis in endothelial cells, in contrast to those of
      bFGF and HGF. On the other hand, bFGF, but not HGF and VEGF, stimulated DNA
      synthesis in VSMC. CONCLUSION: These results demonstrate that HGF can exert
      stimulating effects on endothelial cell growth, but not on VSMC growth, in an
      additive manner with bFGF but not with VEGF. These characteristics of HGF as an
      endothelium-specific growth factor may provide the opportunity for a new
      therapeutic strategy for vascular diseases in which the abnormalities were
      vasoconstriction and pathological growth.

PMID- 8986906
TI  - High end tidal CO2 association with blood pressure response to sodium loading in
      older adults.
AB  - OBJECTIVE: To test the hypothesis that blood pressure of older adults with high
      resting end tidal CO2 (PETCO2) is sensitive to high dietary intake of sodium
      chloride. DESIGN AND METHODS: Forty-four Caucasian men and women, aged 41-79
      years (mean +/- SEM 55.5 +/- 1.4), restricted their dietary intake of sodium
      chloride for 11 days and ingested sodium chloride capsules (an additional 190
      mmol sodium/day) during the last seven of those days. On days 1, 4 and 11,
      resting PETCO2 and blood pressure were monitored for 25 min in the laboratory,
      followed by ambulatory blood pressure monitoring in the natural environment for
      24 h. Overnight urine samples were obtained at days 4 and 11 to estimate
      excretion of sodium and of an endogenous digitalis-like factor (EDLF) that is
      sensitive to changes in plasma volume. RESULTS: Individual resting PETCO2
      remained stable within and between laboratory monitoring sessions and was
      correlated with urinary excretion of the endogenous digitalis-like factor, both
      before and after the period of high sodium intake. The high-sodium diet was
      associated with increased urinary sodium excretion and body weight in all
      quartiles of PETCO2. The high-sodium diet produced significant increases in
      resting and in 24 h systolic blood pressures in the upper two quartiles of the
      PETCO2 distribution, and significant increases in resting and in 24 h diastolic
      blood pressures in the highest PETCO2 quartile only. CONCLUSION: These findings
      indicate blood pressure sensitivity to sodium loading is differentially
      associated with high resting PETCO2 in older adults. A high PETCO2 may be an
      index of a dynamic steady state that influences sodium transport mechanisms.

PMID- 8986907
TI  - Altered cellular calcium responsiveness to insulin in normal and hypertensive
      pregnancy.
AB  - OBJECTIVE: To investigate the glucose-independent calcium-related effects of
      insulin from subjects with normal and hypertensive pregnancies. METHOD: We used
      lndo-l fluorescence spectroscopy to measure cytosolic free calcium levels (Cai)
      in peripheral blood mononuclear cells (PBM) from 17 women (aged 20-40 years), six
      nonpregnant controls (NPC), five pregnant normotensive (PNT) women and six
      pregnant hypertensive (PHT) women, before and 5, 30, 60, 120 and 180 min after in
      vitro incubation with 200 microU/ml insulin. RESULTS: Basal Cai levels were
      significantly higher in PHT women (175.2 +/- 18.8 nmol/l) than they were in NPC
      women (122.8 +/- 2.8 nmol/l) and PNT women (123.9 +/- 3.5 nmol/l). The initial
      insulin-induced rise in Cai was similar in NPC (delta Cai 13.5 +/- 5.6 nmol/l)
      and PNT women (delta Cai 14.6 +/- 3.7 nmol/l), but appeared blunted in PHT women
      (delta Cai 8.2 +/- 3.5 nmol/l), and, for all pregnant subjects, was closely and
      inversely related to basal Cai. Over time, in PNT women, delta Cai did not
      increase from the initial response (maximal delta Cai 20.5 +/- 2.3 nmol/l)
      compared to NPC. The total cellular calcium response to insulin was also blunted
      in PNT women (the area under the calcium-responses curve was 86 +/- 3.4 versus
      97.4 +/- 6.5 nmol/l), but was excessive in PHT women (115.5 +/- 6 nmol/l, P =
      0.05). CONCLUSIONS: Hypertension in pregnancy is associated with excess Cai,
      insulin raises Cai in PBM, and different alterations of Cai responsiveness to
      insulin occur both in normal and in hypertensive pregnancy. These cellular
      calcium alterations may help to explain altered tissue responsiveness to insulin
      and other hormones in pregnancy.

PMID- 8986908
TI  - Effects of beta-adrenergic blockade on insulin-mediated glucose disposal in
      hypertensive and normotensive rats.
AB  - OBJECTIVE: To evaluate the impact of beta-adrenergic blockade in spontaneously
      hypertensive rats (SHR) and in their normotensive controls, Wistar-Kyoto (WKY)
      rats, on whole-body glucose disposal under metabolic steady state conditions, in
      unrestrained and conscious animals. METHOD: SHR (n = 13) and WKY rats (n = 12)
      underwent a 240 min insulinaemic clamp study with or without a super-infusion
      (120th to 240th minutes; second step) of propranolol. RESULTS: From 0 to 120 min
      (the first step) SHR showed significantly increased glucose uptake, muscle
      glycogen synthesis and glycogen synthase activity compared with WKY rats. When
      propranolol was superinfused, glucose uptake and muscle glycogen synthesis in SHR
      returned to levels similar to those observed in WKY rats during the first step.
      No significant differences were found for whole-body glycolysis in SHR and WKY in
      the first and second steps. CONCLUSION: Hypertensive rats display an increased
      insulin sensitivity compared with controls. Beta-Blockade is associated with a
      reduction in overall glucose metabolism in SHR, but not in WKY rats.

PMID- 8986909
TI  - The effect of angiotensin II receptor antagonism with losartan on glucose
      metabolism and insulin sensitivity.
AB  - OBJECTIVE: To investigate the metabolic effects of losartan (Cozaar) in patients
      with essential hypertension. METHODS: Twenty patients with mild hypertension
      (office blood pressure > 140/95 mmHg and home diastolic blood pressure > 90 mmHg)
      were examined in a double-blind, placebo-controlled cross-over study of 4 weeks
      of treatment with 50-100 mg losartan. The effects on glucose metabolism were
      assessed by euglycaemic glucose clamp examinations [glucose disposal rate (GDR,
      mg/kg per min)] and oral glucose-tolerance tests (OGTT). RESULTS: Supine blood
      pressure was reduced from 146 +/- 3/90 +/- 3 mmHg on placebo to 134 +/- 4/83 +/-
      3 mmHg on losartan and the difference was maintained during 120 min of insulin
      infusion and glucose clamping. GDR was 6.2 +/- 0.5 mg/kg per min on placebo and
      6.4 +/- 0.5 mg/kg per min on losartan. The glucose and insulin responses (the
      area under the curve) during OGTT were similar with placebo and losartan (0.86 +/
      0.3 versus 0.88 +/- 0.4 and 341 +/- 60 versus 356 +/- 60, respectively; arbitary
      units). Serum cholesterol was 5.3 +/- 0.2 mmol/l on placebo and 5.1 +/- 0.2
      mmol/l losartan treatment. High-density lipoprotein cholesterol and triglycerides
      were, respectively, 1.1 +/- 0.1 and 1.5 +/- 0.2 mmol/l with placebo, and 1.1 +/-
      0.1 and 1.4 +/- 0.1 mmol/l with losartan treatment. CONCLUSION: In mildly
      hypertensive patients, selective angiotensin II receptor antagonism with losartan
      for 4 weeks lowers blood pressure at rest and during 120 min of glucose clamping,
      and has neutral effects on insulin sensitivity, glucose metabolism and serum
      lipids.

PMID- 8986910
TI  - Evaluation of reproducibility of spontaneous baroreflex sensitivity at rest and
      during laboratory tests.
AB  - OBJECTIVE: The aim of the present study was to examine the reproducibility of
      arterial baroreflex sensitivity (BRS) provided by the spontaneous baroreflex
      method at rest and during laboratory tests. METHODS: Twenty healthy volunteers
      were studied 24 h apart, in the same laboratory and under the same environmental
      conditions, at rest, during active standing, while performing mental arithmetics
      and during static hand-gripping. Systolic blood pressure, mean arterial pressure
      and pulse interval were continuously and non-invasively measured by using a
      Finapres device. BRS was evaluated by analysing the slopes of spontaneously
      occurring sequences of three or more consecutive beats in which systolic blood
      pressure and pulse interval of the following beat both increased or decreased, in
      the same direction, in a linear fashion. Individual BRS were obtained by
      averaging all slopes computed within a given test. RESULTS: Under each test
      condition BRS did not differ significantly between the two consecutive days,
      showing strikingly similar values. The mean group coefficients of variation
      (CVAR), obtained by averaging individual CVAR, between the two experimental days
      were 15.0, 13.9 and 19.7% for resting, standing, static hand-gripping and mental
      arithmetic, respectively. No relationships were found between individual CVAR and
      individual mean arterial pressure, pulse interval and number of baroreflex
      sequences under any tested condition, on both experimental days. CONCLUSIONS:
      These results show that the spontaneous baroreflex method provides good BRS
      reproducibility under various stimuli that affect the neural control of
      circulation differently. They also suggest that BRS variability is dependent
      neither on haemodynamic modifications nor on the degree of baroreflex engagement,
      but it seems to reflect an inherent feature of the way in which arterial
      baroreflex modulate the heart period.

PMID- 8986911
TI  - Relationship between mechanical properties of the carotid artery wall and
      baroreflex function in acutely treated hypertensive patients.
AB  - OBJECTIVE: To evaluate the relationship between the mechanical properties of the
      carotid artery wall and baroreflex function after acute reduction of blood
      pressure with lacidipine in essential hypertension. DESIGN: After 15 days of
      placebo washout, the hypertensive patients underwent a single-blind haemodynamic
      study before and 90 min after administration of 4 mg lacidipine (a
      dihydropyridine calcium antagonist). METHODS: Brachial intra-arterial blood
      pressure was recorded in eight mild-to-moderate essential hypertensive patients
      aged 40-53 years (mean +/- SEM 46.8 +/- 4.7 years). The carotid pulse diameter
      was recorded simultaneously by an echo-tracking technique. The mechanical
      properties of the carotid artery wall were evaluated by calculating Peterson's
      incremental elastic modulus (Ep) both as an averaged value of 10 heart cycles
      with stable blood pressure and was the dynamic correlation, on a beat-to-beat
      basis, of Ep and the systolic blood pressure during a 20 mmHg increase in blood
      pressure following a bolus injection of phenylephrine. The elastic properties of
      the carotid artery were investigated further by determining the correlation
      between the systolic pressure and systolic diameter, beat by beat, during a
      ramped increase of blood pressure after phenylephrine administration. The
      baroreceptor reflex sensitivity was measured simultaneously by the Oxford method
      and by correlating Ep and the electrocardiographic R-R' interval on a beat-to
      beat basis during phenylephrine injections. RESULTS: After lacidipine
      administration Peterson's elastic modulus, measured under resting steady-state
      conditions, was reduced (18.7 +/- 7.4 versus 16.4 +/- 6 x 10(5) dyne/cm2),
      whereas the baroreflex sensitivity was unchanged (6.6 +/- 3.3 versus 6.3 +/- 0.2
      ms/mmHg) and resetting of the baroreflex had occurred. At the same time, the
      correlations between the systolic blood pressure and Ep and between the systolic
      blood pressure and carotid systolic diameter over a 20 mmHg increase in blood
      pressure were unchanged. Moreover, the correlations between the systolic blood
      pressure and the R-R' interval and between Ep and R-R' interval during the
      phenylephrine-induced blood pressure increase did not differ statistically.
      CONCLUSIONS: The results suggest that the resetting of the baroreflex after the
      acute reduction in blood pressure caused by lacidipine is dissociated from
      mechanical changes in the carotid artery wall.

PMID- 8986912
TI  - Decreased developmental cell death in sympathetic and spinal sensory nervous
      systems of the Kyoto spontaneously hypertensive rat.
AB  - OBJECTIVE: To investigate the hypotheses that Kyoto spontaneously hypertensive
      rats (SHR) possess more sympathetic neurons than do normotensive Wistar-Kyoto
      (WKY) animals due to reduced perinatal cell death and that this is due to
      increased availability of the sympathetic survival neurotrophin, nerve growth
      factor. METHODS: Total cell counts of neuron numbers were performed in neonatal
      and adult SHR and WKY rat superior cervical ganglia and correlated with counts of
      apoptotic cells. The values for sympathetic neuron numbers were compared with
      those for a spinal sensory ganglion. Immunocytochemistry was used to obtain more
      information about the phenotypes of neurons counted. RESULTS: Adult SHR
      sympathetic ganglia contained about 25% more sympathetic neurons than did those
      of WKY animals. Similar elevation of numbers was found both for neurons
      containing and for those devoid of neuropeptide Y. In neonatal animals, in
      contrast, there was no strain difference in sympathetic cell numbers but the
      number of apoptotic cells was reduced in SHR. Spinal sensory neuron numbers in
      adult SHR were elevated to a similar extent as were sympathetic neurons, but
      biochemical and morphometric data suggested that this change does not involve
      cells that are sensitive to nerve growth factor. CONCLUSIONS: Although our
      results support the view that there is reduced developmental cell death both in
      sympathetic and in sensory systems, they also suggest that this is unlikely to be
      due to a simple excess of nerve growth factor during development.

PMID- 8986913
TI  - Regression of left ventricular hypertrophy in experimental renovascular
      hypertension: diastolic dysfunction depends more on myocardial collagen than it
      does on myocardial mass.
AB  - OBJECTIVE: To evaluate regression of experimental left ventricular hypertrophy
      (LVH) in terms of its effects both on myocardial collagen levels and on diastolic
      stiffness. METHODS: Two-kidney, one clip Goldblatt hypertensive rats were left
      untreated for 4 weeks (HT4W, n = 12) or 12 weeks (HT12W, n = 11) and compared
      with rats the treatment of which was started after 4 weeks of hypertension with
      30 mg/kg per day losartan for 8 weeks (LOS, n = 12), or 50 mg/l enalapril for 8
      weeks (ENA, n = 11). A group of sham-operated rats served as controls (SHAM, n =
      9). RESULTS: The blood pressure of the rats increased significantly and LVH
      developed both after 4 and after 12 weeks of hypertension. Treatment with
      losartan or enalapril significantly decreased blood pressure and induced complete
      regression of LVH. Myocardial hydroxyproline concentrations increased in groups
      HT4W and HT12W (530 +/- 153 and 581 +/- 111 micrograms/g, respectively) relative
      to that in the SHAM group (421 +/- 22 micrograms/g). None of the treatments
      induced regression of increased myocardial collagen levels. The slopes of the end
      diastolic stress-strain relationships in the isolated beating hearts were
      significantly higher in HT4W, HT12W and in both treated groups compared with
      those in the SHAM group, indicating increased diastolic myocardial stiffness.
      CONCLUSION: Losartan and enalapril treatments decreased blood pressure and
      induced complete regression of LVH in this model of renovascular hypertension. In
      contrast, none of the treatments induced regression of increased myocardial
      collagen levels or reduced the abnormal left ventricular diastolic stiffness.
      These data suggest that diastolic dysfunction depends more on increased
      myocardial collagen levels than it does on myocardial mass in this model of
      pathological LVH.

PMID- 8986914
TI  - Vascular responsiveness in isolated perfused kidneys of diabetic hypertensive
      rats.
AB  - OBJECTIVE: The aim of this study was to investigate whether diabetes and
      hypertension cause additive effects in the responses to various vasoconstrictor
      and vasodilator agents, in isolated perfused kidneys obtained from streptozotocin
      (STZ)-diabetic Wistar-Kyoto (WKY) rats and from diabetic spontaneously
      hypertensive rats (SHR). METHODS: SHR and WKY rats were administered STZ 55 mg/kg
      by intravenous injection into a lateral tail vein at age 12 weeks. Eight weeks
      later the kidneys were isolated and perfused via the left renal artery with a
      physiological salt solution. Renal perfusion pressure was measured continuously.
      Concentration response curves were plotted for various vasoconstrictor and
      vasodilator agents. RESULTS: Both the diabetic and the hypertensive state were
      associated with an increased wet kidney weight. The contractile responses of the
      renal arterial system to phenylephrine (PhE), serotonin (5-HT) and angiotensin II
      (Ang II) in terms both of the maximal rise in perfusion pressure (mmHg) and of
      the sensitivity (log EC50) were the same in preparations from diabetic WKY rats
      and in those from normoglycaemic WKY rats. The maximal contractile responses both
      to PhE and to Ang II were enhanced in kidneys from SHR compared with those in
      kidneys from their normotensive controls, whereas simultaneously occurring
      diabetes impaired this sensitization. After precontraction with 3 x 10(-6) mol/l
      PhE both endothelium-dependent (methacholine) and endothelium-independent (sodium
      nitroprusside) vasodilator drugs caused the same vasodilator response in the
      preparations taken from the four groups of animals. CONCLUSION: In isolated
      perfused kidneys obtained from STZ-diabetic WKY rats and SHR, the isolated
      diabetic state did not influence the vasoconstriction caused by various agonists.
      However, the enhanced vascular reactivity in the hypertensive state was blunted
      by simultaneously occurring diabetes mellitus. Endothelium-dependent and 
      independent vasorelaxation in this model was not affected neither by the
      hypertensive nor by the diabetic state.

PMID- 8986915
TI  - Importance of the renin-angiotensin system in the generation of kidney failure in
      renovascular hypertension.
AB  - OBJECTIVES: To determine the possible relationship between the degree of dietary
      sodium intake and the development of renal failure during blockade of the renin
      angiotensin system. DESIGN: Antihypertensive doses of captopril, an angiotensin
      converting enzyme, and hydralazine, a non-specific vasodilator, were administered
      in sham-operated and two-kidney, two clip Goldblatt hypertensive rats subjected
      to various degrees of dietary sodium intake. METHODS: The blood pressure, water
      intake, urine flow and sodium excretion of the animals were determined before and
      during a 3-day period of drug administration. Plasma concentrations of urea and
      creatinine were measured as indicators of renal function and glomerular
      filtration rate. RESULTS: The blood pressure of the clipped rats was higher than
      that of sham-operated rats (241 +/- 5 versus 150 +/- 4 mmHg), regardless of their
      sodium intake. Captopril administration failed to lower blood pressures of sodium
      replete hypertensive rats, but in hypertensive rats fed either a low- or a 'no'
      sodium diet the blood pressure was reduced by 45 +/- 7 and 127 +/- 19 mmHg,
      respectively. Furthermore, hydralazine reduced blood pressure in hypertensive
      rats fed a 'no'-sodium diet by a similar degree, to 99 +/- 8 mmHg. Captopril, but
      not hydralazine, significantly increased plasma levels of urea and creatinine in
      hypertensive rats fed the 'no'-sodium diet. CONCLUSION: These findings indicate
      that angiotensin II plays an important role in the maintenance of renal function
      during blood pressure reduction by angiotensin converting enzyme inhibition in
      volume-contracted renovascular hypertensive states.

PMID- 8986916
TI  - Antihypertensive effects and arterial haemodynamic alterations during angiotensin
      converting enzyme inhibition.
AB  - OBJECTIVE: To assess the respective roles of the anti-hypertensive and blood
      pressure-independent effects of angiotensin converting enzyme (ACE) inhibition in
      the changed arterial haemodynamics observed in hypertensive patients with end
      stage renal disease (ESRD) treated by haemodialysis. DESIGN AND METHODS: Twelve
      hypertensive patients with ESRD were included in a double-blind, cross-over study
      comparing a single 20 mg dose of the ACE inhibitor quinapril versus placebo. Two
      study periods each of 172 h duration were separated by a 2-week placebo period.
      Repeated measurements of the following parameters were performed: brachial artery
      systolic blood pressure (SBP); diastolic blood pressure and mean blood pressure
      (using a mercury sphygmomanometer); carotid artery SBP and pulse pressure (by
      applanation tonometry); aortic stiffness (by pulse wave velocity); and the effect
      of arterial wave reflections in the common carotid artery (the augmentation
      index, by applanation tonometry). A radioimmunoassay was used to determine plasma
      angiotensin II levels. Quinaprilat pharmacokinetics were studied using a specific
      assay. Two-way (time-treatment) analysis of variance for repeated measures,
      analysis of covariance for two within-factors and a covariate changing with the
      level of the factor time (pressures measured at each time) and baseline values of
      the studied parameter as a second covariate were used for statistical analysis.
      RESULTS: Quinapril treatment induced a long-lasting decrease in arterial wave
      reflections, which was still observable 172 h after quinapril administration and
      still present after removing the effect of the decrease in blood pressure. The
      effect on wave reflections was associated with a more pronounced and sustained
      decrease in carotid SBP and pulse pressure than that in brachial SBP and pulse
      pressure. Quinapril administration also induced a long-lasting decrease in aortic
      pulse wave velocity, but this effect was entirely dependent on parallel changes
      in blood pressure. Arterial haemodynamic changes were not related to plasma
      angiotensin II or quinaprilat levels. CONCLUSIONS: The results of this controlled
      study indicate that, in ESRD patients, ACE inhibition results in a long-lasting,
      blood pressure-independent decrease in arterial wave reflections. The consequence
      of this was a decrease in pulsatile pressure load in the central arteries with
      increased aortic distensibility. The increased aortic distensibility resulted
      from the decrease in blood pressure. The observed arterial haemodynamic
      alterations suggest that ACE inhibition induced alterations in arterial wave
      reflections in the distal parts of the arterial tree.

PMID- 8986917
TI  - Valsartan, a new angiotensin II antagonist for the treatment of essential
      hypertension: efficacy and safety compared with placebo and enalapril.
AB  - OBJECTIVE: To compare the antihypertensive efficacy and systemic tolerability of
      valsartan, a new angiotensin II receptor antagonist, with placebo and with an
      angiotensin converting enzyme (ACE) inhibitor, enalapril. DESIGN: A total of 348
      adult outpatients with mild-to-moderate uncomplicated essential hypertension
      participated in this double-blind, parallel, study. Patients were allocated
      randomly in a ratio of 2:2:1 to receive 80 mg valsartan once a day, 20 mg
      enalapril once a day, or placebo for 8 weeks in general practice. Patients were
      assessed at 4 and 8 weeks of therapy. MAIN OUTCOME MEASURES: The primary efficacy
      variable was the change from baseline in mean sitting diastolic blood pressure
      (SDBP) after 8 weeks of therapy. Secondary variables included the change in
      sitting systolic blood pressure (SSBP) and response rates at 8 weeks. RESULTS:
      Valsartan and enalapril produced statistically significant reductions in
      diastolic and systolic blood pressures compared with placebo. Similar falls were
      found in both of the active treatment groups with mean changes in SDBP at 8 weeks
      of -9.5 mmHg for valsartan and -9.4 mmHg for enalapril (-4.5 mmHg for placebo).
      No significant differences between valsartan and enalapril were found for
      reductions in SDBP or SSBP. Response rates at 8 weeks were significantly greater
      for valsartan (54%) and enalapril (58%) than for placebo (20%), with no
      significant difference between the two active treatments. Both valsartan and
      enalapril demonstrated a consistent antihypertensive effect over time, with 90%
      of patients with a response at 4 weeks responding at 8 weeks. Both of the
      treatments were tolerated well. Although the incidence of coughing was generally
      low in the study, more cases were reported with enalapril (three) than with
      valsartan (one) or placebo (none). CONCLUSIONS: The data show 80 mg valsartan
      once a day to be as effective as 20 mg enalapril once a day in the treatment of
      mild-to-moderate hypertension. Valsartan is tolerated well and does not appear to
      be associated with any increase in the incidence of coughing.

PMID- 8986918
TI  - Sodium-lithium countertransport.

PMID- 8986919
TI  - Epithelial sodium channels and hypertension.

PMID- 8986920
TI  - Altered myogenic responsiveness of the renal microvasculature in experimental
      hypertension.
AB  - Recent investigations have delineated the renal microvascular responsiveness to
      pressure, by using isolated afferent arterioles, juxtamedullary nephrons, and
      isolated perfused hydronephrotic kidneys. Both afferent arterioles and
      interlobular arteries (ILA) manifest pressure-dependent vasoconstrictor responses
      to elevated renal arterial pressure. Several recent studies have indicated that
      the afferent arteriole adjacent to the glomerulus constricts primarily in
      response to tubuloglomerular feedback signals, whereas the afferent arteriole
      near the ILA is under the dominant influence of myogenic tone. Furthermore, the
      responsiveness of the ILA to pressure is dependent on the basal diameter, with
      the smaller diameter (distal) segments demonstrating more marked responses than
      do the larger (proximal) segments. The myogenic afferent arteriolar response is
      shifted to higher perfusion pressure in spontaneously hypertensive rat (SHR)
      kidneys, and blunted both in Dahl salt-sensitive rats and in Goldblatt renal
      hypertensive rats. This altered responsiveness of the afferent arteriole may
      account for the alterations in renal blood flow autoregulation, namely, resetting
      toward higher pressures in SHR, and impairment in Dahl salt-sensitive rats and
      Goldblatt hypertensive rats Distal ILA segments vasoconstricted similarly in
      response to pressure both in SHR and in Wistar-Kyoto rats (WKY), whereas proximal
      ILA segments did not exhibit vasoconstriction in either strain. The intermediate
      ILA segment from SHR kidneys manifests more prominent myogenic vasoconstriction
      than does that from WKY rat kidneys. The enhanced myogenic responsiveness of the
      intermediate ILA segment may act in concert with afferent arteriolar
      vasoconstriction to prevent glomerular hypertension in superficial nephrons.
      Finally, the myogenic vasoconstriction of renal microvessels is mediated in part
      by voltage-dependent calcium channels, and the altered myogenic response may be
      associated with modified activity of voltage-dependent calcium channels. Thus,
      the myogenic preglomerular tone constitutes a pivotal determinant of renal
      autoregulation, and teleologically may also play an important role in protecting
      glomeruli from barotrauma in hypertension, whereas the functional myogenic
      element is soon reinforced by an element of "structural autoregulation' of
      preglomerular resistance vessels.

PMID- 8986921
TI  - Relationship between the angiotensin converting enzyme gene polymorphism and the
      effects of enalapril on left ventricular hypertrophy and impaired diastolic
      filling in essential hypertension: M-mode and pulsed Doppler echocardiographic
      studies.
AB  - OBJECTIVE: To investigate the relationship between the angiotensin converting
      enzyme (ACE) gene polymorphism and the effects of the ACE inhibitor enalapril on
      left ventricular hypertrophy and impaired diastolic filling. DESIGN AND METHODS:
      Enalapril (5-10 mg/day) was administered for 12 months to 60 previously untreated
      patients with essential hypertension. M-mode and pulsed Doppler echocardiography
      were performed before and after treatment, and changes in various parameters
      after treatment with enalapril were examined. ACE gene polymorphism was examined
      by the polymerase chain reaction method and the patients were classified as
      having the 190 bp deletion homozygous (DD) genotype, the 490 bp insertion
      homozygous (II) genotype or the 490 bp insertion 190 bp deletion heterozygous
      (ID) genotype. RESULTS: The DD genotype was observed in 10 patients (17%), the ID
      genotype in 24 patients (40%) and the II genotype in 26 patients (43%). Plasma
      ACE activity before treatment with enalapril was significantly higher in seven
      patients with DD genotype than it was in 18 patients with ID genotype and in 14
      patients with II genotype. In all of the 60 patients, the left ventricular mass
      index, the peak atrial systolic velocity:early diastolic velocity ratio and the
      deceleration time from the peak of the early diastolic wave to the baseline in
      transmitral flow velocity were decreased significantly after treatment with
      enalapril. The changes in left ventricular mass index and atrial systolic
      velocity:early diastolic velocity ratio after enalapril administration were
      significantly greater in the DD genotype group than they were in the other two
      genotype groups. CONCLUSION: Enalapril-induced regression of left ventricular
      hypertrophy and improvement in left ventricular impaired diastolic filling were
      significantly greater in the DD genotype group than they were in the ID and II
      genotype groups, suggesting that the circulating and tissue renin-angiotensin
      systems, particularly the former system, are most active in hypertensive patients
      with the DD genotype.

PMID- 8986922
TI  - Regulation of type 1 angiotensin II receptor and its subtype gene expression in
      kidney by sodium loading and angiotensin II infusion.
AB  - OBJECTIVE: To test the hypothesis that a high salt intake decreases gene
      expression of both type 1 angiotensin receptor subtypes 1A and 1B (AT1A and AT1B)
      and diminishes AT1 receptor density in the kidney through an angiotensin II (Ang
      II)-independent mechanism. METHODS: Wistar rats were divided into four groups and
      fed a normal-sodium diet (0.5%, NSD), NSD + 25 ng/kg per min Ang II infusion, a
      high-sodium diet (4%, HSD), or HSD + Ang II infusion for 2 weeks. Quantitative
      reverse transcriptase-polymerase chain reaction was used for analysis of changes
      in renal AT1A and AT1B messenger RNA (mRNA) levels. Radioligand binding assays
      were used for measurement of Ang II receptor density. RESULTS: Body weight and
      mean arterial pressure did not differ among the four groups. Renal AT1A and AT1B
      mRNA levels were decreased significantly in NSD + Ang II and HSD + Ang II groups
      compared with those in the NSD group. Renal AT1B mRNA was also decreased
      significantly in HSD versus NSD. The renal AT1 receptor density was decreased
      significantly in NSD + Ang II and HSD + Ang II, but was not changed in HSD
      compared with NSD. CONCLUSION: A high salt intake downregulates the AT1B mRNA
      expression but does not change the AT1A mRNA expression and AT1 receptor density
      in the kidney, suggesting that differential regulation occurs in the kidney.
      Infusion of a nonpressor dose of Ang II, either alone or in conjunction with a
      high salt intake, downregulates the AT1 receptor and its subtype gene expression
      in the kidney, suggesting that Ang II regulates these responses through a
      negative feedback mechanism.

PMID- 8986923
TI  - Lack of mutations in epithelial sodium channel beta-subunit gene in human
      subjects with hypertension.
AB  - OBJECTIVE: To investigate a possible role for mutations of the epithelial sodium
      channel in patients with essential hypertension. DESIGN: A cross-sectional study
      screening essential hypertension patients and normotensive controls for the
      presence of a genetic abnormality in the epithelial sodium channel beta-subunit
      in the Japanese population. SETTING: An institutional teaching hospital. PATIENTS
      AND PARTICIPANTS: Ninety Japanese patients with essential hypertension and 51
      normotensive controls were investigated. The hypertensive patients were
      consecutive samples from our hypertension clinics. It was required that they had
      had a previous history of systolic blood pressure higher than 160 mmHg or
      diastolic higher than 95 mmHg. Secondary hypertension was excluded by clinical
      presentation or appropriate laboratory examinations. Normotensive subjects were
      patients visiting our outpatient clinics without evidence or a history of
      hypertension. It was required that they had systolic blood pressures less than
      160 mmHg and diastolic blood pressures less than 90 mmHg, and that they were aged
      above 60 years. INTERVENTIONS: Genomic DNA from each subject was purified from
      whole blood and was used as the template for polymerase chain reaction
      amplification of the carboxy-terminal portion of the epithelial sodium channel
      beta-subunit. Amplified DNA segments were screened for genetic mutations by
      direct sequencing. MAIN OUTCOME MEASURE: Genetic mutations of the epithelial
      sodium channel beta-subunit. RESULTS: No significant genetic mutation was
      detected in any of the hypertensive and normotensive subjects, except for a
      polymorphism found in three subjects (two hypertensives and one normotensive).
      CONCLUSION: Mutations of the carboxy-terminal portion of the epithelial sodium
      channel beta-subunit were not identified in an unselected cohort of patients with
      essential hypertension from the Japanese community.

PMID- 8986924
TI  - Seasonal variations in office, home and 24 h ambulatory blood pressure in
      patients with essential hypertension.
AB  - OBJECTIVE: To study the influence of seasons on blood pressure in ordinary
      circumstances. DESIGN AND METHODS: We examined seasonal variations of home and 24
      h ambulatory and office blood pressures in outpatients with essential
      hypertension. Office, home and ambulatory blood pressures of 50 outpatients with
      essential hypertension were recorded in 1993. The subjects were 26 women and 24
      men, aged 59.3 +/- 1.1 years (mean +/- SEM). Office blood pressure was measured
      monthly by physicians. Home blood pressure was measured every day by the patients
      in the morning and evening. Ambulatory blood pressure was recorded every 30 min
      in summer and in winter. The order of ambulatory blood pressure monitoring was
      randomized. The daytime and night-time blood pressures were calculated according
      to the true waking and sleeping times of the individual patients. RESULTS: Both
      office and home blood pressures showed significant seasonal variations. The
      winter-summer differences in office and home blood pressures were 4.7 +/- 1.3/
      3.3 +/- 0.9 and 5.9 +/- 1.1/2.7 +/- 0.6 mmHg, respectively. They were not
      influenced by the presence of antihypertensive agents. The winter-summer
      difference was also significant for daytime ambulatory blood pressure (3.5 +/-
      1.4/ 2.5 +/- 0.8 mmHg), but not for night-time ambulatory blood pressure (-2.9 +/
      1.7/-1.2 +/- 1.0 mmHg) or average 24 h blood pressure (1.5 +/- 1.3/1.2 +/- 0.7
      mmHg). There were no significant differences in the waking and sleeping times
      between the two seasons. CONCLUSIONS: Office, home and daytime ambulatory blood
      pressure levels were higher in winter than they were in summer in patients with
      essential hypertension. However, the seasonal variations in average 24 h blood
      pressure may be small because of the lack of changes in night-time blood
      pressure.

PMID- 8986925
TI  - Sleep and blood pressure: spontaneous baroreflex sensitivity in dippers and non
      dippers.
AB  - OBJECTIVE: Baroreflex sensitivity (BRS) increases during sleep, whereas arterial
      blood pressure falls. Some hypertensive patients do not have a nocturnal fall in
      blood pressure (non-dippers). The objective was to ascertain whether there is a
      difference between 24 h BRS values in dippers and non-dippers that might account
      for the difference in nocturnal blood pressure behaviour. DESIGN: In a group of
      consecutive untreated hypertensive patients undergoing 24 h ambulatory intra
      arterial blood pressure (IABP) monitoring, 18 were non-dippers i.e., their mean
      IABP during sleep failed to drop by 10% of their waking IABP. Each non-dipper was
      matched for age and waking IABP with two dippers. The BRS had previously been
      assessed with the "Oxford' bolus phenylephrine technique; spontaneous BRS was
      assessed throughout the 24 h period by off-line computer analysis of spontaneous
      variations in IABP and R-R interval. RESULTS: In both groups there was a
      significant increase in spontaneous BRS during sleep (P < 0.0001 for dippers, P <
      0.0001 for non-dippers). There was no significant difference between spontaneous
      BRS in dippers and non-dippers, when they were either awake or asleep.
      CONCLUSION: BRS did not differ significantly between dippers and non-dippers,
      when they were either awake or asleep. Changes in BRS during sleep are not likely
      to account for the abnormal dipping pattern in a minority of hypertensives and
      are not likely to contribute to the normally observed nocturnal fall in blood
      pressure.

PMID- 8986926
TI  - Prevalence of carotid atherosclerosis in middle-aged hypertensive and control
      subjects. A cross-sectional systematic study with duplex ultrasound.
AB  - BACKGROUND: Arterial hypertension has been found to increase atherosclerotic
      lesions, although contradictory results have suggested that hypertension has
      little or no effect. These discrepancies are probably caused by differences in
      populations. OBJECTIVE: To examine the effect of hypertension on carotid
      atherosclerosis in a population-based series of patients with an established
      diagnosis of arterial hypertension and controls. METHODS: Carotid intima-media
      thickness (IMT) and plaques were evaluated with duplex ultrasound in 1031 middle
      aged (aged 40-60 years) men (n = 511) and women (n = 520), 513 with arterial
      hypertension and 518 controls. IMT was measured in the internal carotid artery,
      bifurcation and proximal, middle and distal common carotid artery, determining
      mean and maximal values for each patient. RESULT: Male sex, age, smoking and
      cholesterol were the most significant risk factors for combined plaque and intima
      media thickness (CPIMT); hypertension and and abnormal glucose test result were
      further significant risk factors. There was a significant difference in CPIMT
      between the hypertensive and control subjects, but this was caused by the
      differences in the men; there were no statistically significant differences among
      the women. Plaques were found more frequently in the hypertensive men than they
      were in their controls (62.8 versus 49.8%), the corresponding percentages for the
      hypertensive and control women being 38.0 and 32.1%. There was a larger
      proportion of male subjects with a long duration of hypertension (> or = 7 years)
      who had plaques and greater CPIMT than there was of those with a short duration
      of hypertension. CONCLUSION: Hypertension had a significant effect on CPIMT and
      on the prevalence of plaques in men, but its effect in women was not significant.
      A long duration of hypertension resulted in greater CPIMT values and a higher
      prevalence of plaques, particularly in men.

PMID- 8986927
TI  - Left ventricular concentric remodelling and carotid structural changes in
      essential hypertension.
AB  - AIM: Left ventricular concentric remodelling defines a modified left ventricular
      geometry in the presence of a normal left ventricular mass; it is an early and
      frequent adaptation in arterial hypertension. The present study was designed to
      evaluate the extent of carotid structural changes in essential hypertensives with
      left ventricular remodelling. PATIENTS AND METHODS: Two groups of hypertensive
      patients, who had never previously received anti-hypertensive treatment, 14 with
      left ventricular concentric remodelling (group I, relative wall thickness 0.48 +/
      0.02) and 48 with normal left ventricular geometry (group II, relative wall
      thickness 0.37 +/- 0.04) underwent clinical and laboratory examination,
      echocardiography, carotid artery ultrasonography and 24 h ambulatory blood
      pressure monitoring (ABPM). The left ventricular dimensions and mass were
      obtained according to the Penn convention. The intima-media thickness (IMT) of
      the posterior wall of both common carotid arteries was measured 5, 10 and 20 mm
      caudally to the bulb and the average value was used for analysis. RESULTS: In
      both groups age (group I 44 +/- 9 years; group II 40 +/- 9 years), body surface
      area (group I 1.85 +/- 0.2 m2; group II 1.80 +/- 0.2 m2), duration of
      hypertension (group I 4.4 +/- 4; group II 3.8 +/- 3.9 years), metabolic
      parameters and smoking habits were similar. Both clinic and 24 h ABPM values were
      higher in group I (clinic 157 +/- 12/102 +/- 5; 24 h ABPM 145 +/- 10/95 +/- 7
      mmHg) than they were in group II (clinic 146 +/- 11/97 +/- 5; 24 h ABPM = 134 +/-
      10/87 +/- 8 mmHg, P < 0.01). The left ventricular mass index (LVMI) and IMT were
      found to be slightly but significantly greater in group I than they were in group
      II (LVMI 106 +/- 7 versus 98 +/- 12 g/m2, P < 0.05; IMT 0.68 +/- 0.13 versus 0.61
      +/- 0.10 mm, P < 0.05). A significant correlation was found between LVMI and
      common carotid IMT in the whole group of hypertensive patients (r = 0.43, P <
      0.01). CONCLUSIONS: Our results indicate that left ventricular concentric
      remodelling does not represent the only early cardiovascular change in arterial
      hypertension but rather is associated often with carotid intima-media thickening.

PMID- 8986928
TI  - Fixed-dose combination of perindopril with indapamide in spontaneously
      hypertensive rats: haemodynamic, biological and structural effects.
AB  - OBJECTIVE: The present study was designed to test the effects of chronic combined
      treatment with low doses of an angiotensin converting enzyme inhibitor
      (perindopril) and of the diuretic indapamide in spontaneously hypertensive rats
      (SHR). METHODS: Adult SHR were treated with placebo or increasing doses of the
      combination of the drugs (0.3, 1 and 3 mg/kg per day; ratio of doses 0.32). In a
      separate set of experiments, the effects of the drugs combined (1 mg/kg per day)
      was compared with those induced by each drug alone. RESULTS: The drug combination
      dose-dependently decreased systolic blood pressure and its hypotensive effect was
      more marked than those induced by each treatment administered alone (untreated
      208 +/- 5 mmHg, indapamide 185 +/- 5 mmHg, perindopril 150 +/- 3 and the
      combination 123 +/- 7 mmHg). A 12-week treatment with the drug combination (1
      mg/kg per day) was not accompanied by any change in diuresis or urinary excretion
      of Na or K. The same treatment decreased cardiac hypertrophy and collagen. At the
      vascular level, the drug combination decreased aortic, carotid and femoral media
      cross-sectional areas, as well as aortic and carotid collagen density. This
      latter effect was accompanied by a significant increase in carotid artery
      compliance assessed in vivo at constant pressure. Finally, in isolated aortae,
      chronic combined drug treatment was associated with an increased basal release of
      nitric oxide and a decrease in the hypertension-induced endothelium-dependent
      contractions in response to acetylcholine. CONCLUSION: These experiments suggest
      that chronic combined treatment with low doses of an angiotensin converting
      enzyme inhibitor and a diuretic such as indapamide may be of value in the
      treatment of hypertension.

PMID- 8986929
TI  - Reproducibility of the response to short-term low salt intake in essential
      hypertension.
AB  - BACKGROUND: The reproducibility of the arterial pressure response to change in
      salt intake in essential hypertensives has been little investigated. OBJECTIVE:
      To study the reproducibility of the response to salt in 14 untreated patients
      with mild essential hypertension. METHODS: After a run-in phase (1 month), each
      patient ingested, in random order and with cross-over, 1 week of high salt intake
      (170 mmol/day) and 1 week of low salt intake (40 mmol/day). The identical
      experimental protocol was then repeated after an average interval of 3.4 months.
      Arterial pressure was measured (clinic arterial pressure and 24 h ambulatory
      monitoring) on the seventh day of each diet period. The reproducibility of the
      arterial pressure response was assessed in terms the intraclass correlation
      coefficient and the K statistics. RESULTS: There was a good compliance with the
      dietary prescription because the urinary Na excretion was on average very close
      to the prescribed intake both during the first and during the second salt intake
      period. Both clinic and 24 h arterial pressure fell significantly (P < 0.01) and
      to the same extent in the low-salt phases of the study. Clinic arterial pressure
      was consistently higher than 24 h ambulatory arterial pressure but the average
      changes induced by salt depletion were similar. The variability of 24 h
      ambulatory arterial pressure at constant salt intake was lower than that of
      clinic arterial pressure. However, the arterial pressure response to salt showed
      the same variability with the two methods. The reproducibility of the dichotomous
      classification of patients into salt-sensitive and -resistant was low both in
      terms of 24 h ambulatory and in terms of clinic blood pressure. CONCLUSION:
      Although on rechallenging the average arterial pressure response to salt remains
      unchanged in essential hypertensives, the individual responses are variable and
      the reproducibility of the dichotomous classification is unsatisfactory. The
      problem of dichotomizing patients into salt-sensitive and -resistant ones is only
      in very little part resolved by more precise arterial pressure estimates.

PMID- 8986930
TI  - Is salt-sensitivity of blood pressure a reproducible phenomenon-commentary.

PMID- 8986931
TI  - High sodium sensitivity and glomerular hypertension/hyperfiltration in primary
      aldosteronism.
AB  - OBJECTIVE: To assess sodium sensitivity and glomerular haemodynamics in patients
      with primary aldosteronism. DESIGN AND METHODS: Two-week studies were performed
      in six patients with primary aldosteronism whose diagnosis had been confirmed by
      histology of the removed adrenal adenoma. Patients were fed normal or sodium
      restricted diets for 1 week each and renal clearance measured during the normal
      sodium diet. Pressure-natriuresis relationships were drawn by plotting the
      urinary sodium excretion on the y-axis as a function of the systemic mean
      arterial pressure on the x-axis. RESULTS: The extrapolated x-intercept of the
      pressure-natriuresis curve was 118 +/- 9 mmHg. The sodium sensitivity, which
      corresponds to the reciprocal of the slope, was augmented to 0.111 +/- 0.013
      mmHg/mmol per day, and the reduction in mean arterial pressure by sodium
      restriction was 11 +/- 2%. As we had reported previously, the difference between
      the mean arterial pressure (137 +/- 5 mmHg) with the normal-sodium diet and the x
      intercept was assumed to be the effective filtration pressure across the
      glomerular capillary walls (18.2 +/- 2.0 mmHg). By dividing the glomerular
      filtration rate (128 +/- 10 ml/min per 1.73 m2) by the effective filtration
      pressure, the whole kidney ultrafiltration coefficient in these patients was
      estimated to be 0.127 +/- 0.021 ml/s per mmHg, which was approximately normal.
      The glomerular capillary pressure was calculated to be 54 +/- 2 mmHg. CONCLUSION:
      Compared with non-sodium-sensitive essential hypertension patients (n = 18) whose
      glomerular filtration rate and capillary hydraulic pressure were 84 +/- 3 ml/min
      per 1.73 m2 and 47 +/- 1 mmHg, the sodium sensitivity of blood pressure in
      patients with primary aldosteronism was augmented, and both glomerular hyper
      filtration and glomerular capillary hypertension were observed. We confirmed that
      the glomerular haemodynamic characteristics in primary aldosteronism are typical
      of those expected for sodium-sensitive hypertension caused by enhanced tubular
      sodium reabsorption.

PMID- 8986932
TI  - Insulin sensitivity following treatment with the alpha 1-blocker bunazosin retard
      and the beta 1-blocker atenolol in hypertensive non-insulin-dependent diabetes
      mellitus patients.
AB  - OBJECTIVE: To compare the effects of the alpha 1-blocker bunazosin retard and the
      beta 1-blocker atenolol (Uniloc) on insulin sensitivity and glucose and lipid
      homeostasis in patients with type-2 diabetes and hypertension. METHODS: Patients
      with controlled type-2 diabetes (non-insulin-dependent diabetes mellitus),
      treated by diet or oral sulphonylurea derivatives, and with mild-to-moderate
      hypertension were include in a randomized, parallel group, double-blind,
      multicentre study. After a single-blind placebo run-in period lasting 4-6 weeks,
      the patients were treated either with bunazosin retard or with atenolol for a
      further 16 weeks including an initial dose titration period to achieve blood
      pressure control. Treatment involved 3, 6 or 12 mg bunazosin retard tablets or
      25, 50 or 100 mg atenolol tablets, administered orally once a day and prescribed
      according to blood pressure response. The euglycaemic hyper-insulinaemic clamp
      technique was used to assess insulin sensitivity both after the placebo period
      and after the active treatment. A total of 95 patients was enrolled in the study
      (placebo phase). Forty-eight patients were withdrawn from the placebo phase,
      mainly due to their blood pressures being outside the required range (seated
      diastolic blood pressure 90-114 mmHg) and 47 patients were allocated randomly to
      active treatment. Of these, 23 were administered bunazosin retard and 24
      atenolol. All evaluations were on an intention-to-treat basis. RESULTS: Insulin
      sensitivity assessed as glucose utilization during the clamp was significantly
      higher following bunazosin retard compared with following atenolol administration
      (3.52 +/- 0.27 versus 2.86 +/- 0.19 units of metabolic clearance rate of glucose
      index, P < 0.05). The insulin level attained during clamps (infusion rate 56
      mU/m2 per min) was higher (P < 0.05) following atenolol (117 +/- 5 mU/l) than it
      was following bunazosin retard administration (102 +/- 5) or placebo (108 +/- 3),
      possibly due to an impaired insulin clearance. Compared with placebo, atenolol
      treatment resulted in significantly increased glucosylated haemoglobin whereas
      bunazosin retard had no significant effect. The two drugs did not show any
      consistent differences in lipid profile or fibrinogen and plasminogen activator
      inhibitor 1 levels. During the study seven serious adverse events were reported
      and one was reported shortly after completion of the study. All except one were
      classified as not related to the study drug and five of them occurred during
      placebo treatment. The non-serious side effects were in general considered to be
      either unrelated to the test drugs or expected effects of the two respective drug
      classes. Both bunazosin retard and atenolol displayed acceptable safety profiles.
      CONCLUSION: Bunazosin retard treatment in hypertensive non-insulin-dependent
      diabetes mellitus patients appears to be associated with a slightly higher
      insulin sensitivity than is atenolol.

PMID- 8986933
TI  - Insulin resistance in patients with a recent diagnosis of coronary artery
      disease.
AB  - OBJECTIVE: To elucidate whether insulin resistance is present in coronary artery
      disease (CAD) at diagnosis and to study its relationship with other known
      cardiovascular risk factors. METHODS: We evaluated the incidence of insulin
      resistance in 40 newly diagnosed CAD patients. Fifteen healthy subjects were used
      as a control group. The patients and controls had no previous history of
      metabolic disorders, and were not being administered any medication that might
      have affected their insulin sensitivity. Immediately after diagnosis of CAD, a
      standard 75 g oral glucose-tolerance test (OGTT) and an insulin suppression test
      (IST) were performed on separate days. The IST consisted of a constant infusion
      of glucose, insulin and somatostatin for 150 min; insulin resistance was
      estimated by determining the steady-state plasma glucose (SSPG) concentrations
      during the last 60 min of the test. The insulin sensitivity index (ISI) was
      calculated by the formula ISI = (glucose infusion rate/SSPG]x10(3). RESULTS:
      Insulin resistance, defined by an ISI below the normal range derived from the
      control group, was present in 82.5% of the CAD patients. As a group, the patients
      with CAD displayed lower ISI (means +/- SD:29.23 +/- 11.23 versus 50.33 +/- 9.37
      dl/kg per min, P < 0.001) than did controls. Serum triglycerides and uric acid
      were higher and high-density lipoprotein cholesterol levels were lower in
      patients than they were in controls. No differences were observed in fasting
      plasma insulin, glucose, total and low-density lipoprotein cholesterol
      concentration. An abnormal OGTT result was observed in 27 patients. The ISI was
      low in 88.8% of the patients with an abnormal OGTT result and in 69% of the 13
      patients with a normal OGTT result. CONCLUSIONS: Insulin resistance and even
      impaired glucose tolerance are common findings in CAD at diagnosis. The changes
      in the lipid profile and in uric acid levels paralleled the changes in insulin
      sensitivity. These results suggest that insulin resistance might play a role in
      the development of coronary atherosclerosis and that its early diagnosis might be
      important in the prophylaxis of CAD.

PMID- 8986934
TI  - Plasma lipids, erythrocyte membrane lipids and blood pressure of hypertensive
      women after ingestion of dietary oleic acid from two different sources.
AB  - OBJECTIVE: To study the effect of a diet rich in mono-unsaturated fatty acids
      (MUFA), from high-oleic sunflower oil (HOSO) and olive oil, on plasma lipids,
      erythrocyte membrane lipids (including fatty acid composition) and blood pressure
      of hypertensive (normocholesterolaemic or hypercholesterolaemic) women. METHODS:
      There were 16 participants who were hypertensive women aged 56.2 +/- 5.4 years.
      The participants ate a diet enriched with HOSO or olive oil for two 4-week
      periods with a 4-week washout period before starting the second type of MUFA
      diet. At entry and during study of each diet, plasma lipids and apolipoproteins
      were measured by conventional enzymatic methods. Erythrocyte membrane lipid and
      fatty acid compositions were analysed by means of the latroscan thin-layer
      chromatography/flame ionization detection technique and by gas chromatography,
      respectively. Blood pressure was also measured. The statistical analysis was
      conducted by using Student's two-tailed paired t-test. RESULTS: In both groups of
      hypertensive patients, there was a significant increase in plasma high-density
      lipoprotein (HDL) cholesterol concentration after the HOSO or olive oil diets,
      with regard to baseline. Additionally, a significant decrease in plasma HDL2
      cholesterol concentration and an increase in plasma HDL3 cholesterol
      concentration were evident. The membrane free-cholesterol concentration increased
      significantly and the phospholipid concentration decreased significantly in
      erythrocytes after the olive oil diet, though both MUFA diets produced a
      significant decrease in the concentration of membrane esterified cholesterol.
      Therefore, the molar ratio of cholesterol to phospholipids was raised
      significantly in the erythrocyte membrane of hypertensive women after the dietary
      olive oil, but not after the HOSO diet. In the hypertensive and normo
      cholesterolaemic group the HOSO diet significantly increased the content in the
      erythrocyte membrane of oleic, eicosenoic, arachidonic and docosapentaenoic
      acids, whereas the olive oil diet increased the content of palmitoleic acid and
      long-chain polyunsaturated fatty acids of the n-3 family besides, compared with
      baseline. A significant decrease in linoleic acid was also evident. In the
      hypertensive and hypercholesterolaemic group, the HOSO diet resulted in
      significant increases in palmitoleic, oleic, eicosenoic and behenic acids,
      whereas the olive oil diet enhanced the content of arachidonic, docosapentaenoic
      and docosahexaenoic acids besides, with respect to baseline. In addition, there
      was a significant decrease in stearic acid, but only after dietary olive oil was
      there a decrease in linoleic acid. The most important differences between the two
      MUFA diets were the increase in n-3 fatty acids and the decrease in the n-6; n-3
      fatty acids ratio after dietary olive oil in the erythrocyte membranes of
      hypertensive patients. Interestingly, a significant reduction in systolic and
      diastolic blood pressures was only evident after the ingestion of olive oil.
      CONCLUSION: These data suggest that the beneficial effects of dietary olive oil
      on the plasma lipids and lipoprotein profile, lipid and fatty acid composition of
      erythrocyte membrane, and blood pressure in women with untreated essential
      hypertension are not found equally for the HOSO-rich diet, despite both vegetable
      oils providing a similar concentration of MUFA.

PMID- 8986935
TI  - Sodium, potassium and blood pressure.

PMID- 8986936
TI  - Treatment guidelines in hypertension: current limitations and future solutions.
AB  - AREAS OF AGREEMENT: Among the many guidelines and recommendations put forward by
      national and international authorities in recent years, there has been close
      agreement that the physician should assess each patient carefully over many
      months, should address the total profile of cardiovascular risk not just the
      raised blood pressure, and should treat patients right up to the age of 85 years
      with either classical essential hypertension or isolated systolic hypertension.
      The major guidelines described five groups of first-line antihypertensive drugs:
      diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, calcium
      antagonists and alpha-blockers. AREAS OF UNCERTAINTY: In other areas, the various
      guidelines were either united in uncertainty, or divided on the best course of
      action. The availability of many new methods and approaches for the measurement
      of blood pressure has introduced greater uncertainty into the interpretation of
      the blood pressure level in the individual patient, with question marks still
      surrounding the interpretation of white-coat hypertension, of ambulatory blood
      pressure monitoring and of home blood pressure readings in relation to clinic
      blood pressure. There is lack of uniformity in recommendations for the threshold
      values at which raised blood pressure should be lowered and in the
      recommendations for the target blood pressure the physician should set in the
      individual patient. CHOICE OF DRUG TO INITIATE TREATMENT: Since the publication
      of the major guidelines in 1993 and 1994, the greatest uncertainty has surrounded
      the choice of drugs to initiate treatment. This reflects the fact that so far no
      major trials have been completed confirming that the newer agents such as ACE
      inhibitors, calcium antagonists or alpha-blockers reduce cardiovascular morbidity
      and mortality in hypertensive patients. While awaiting the results of the many
      prospective randomized trials that are in progress with these newer agents, a
      number of case-control studies have raised concerns that non-potassium-sparing
      diuretics may increase the incidence of sudden cardiac death and that calcium
      antagonists might increase the occurrence of coronary heart disease in
      hypertensive subjects. CURRENT ACTION: These issues highlight the importance of
      initiating prospective, randomized, controlled trials early in the development of
      all new drugs. While awaiting the results of trials currently in progress, the
      physician should continue to use all five groups of antihypertensive drugs,
      tailoring the choice of drug to suit the individual patient, and should use low
      doses of antihypertensive drugs either alone, or in appropriate combinations.

PMID- 8986937
TI  - Antihypertensive therapy debate: contribution from the Shanghai Trial Of
      Nifedipine in the Elderly (STONE).
AB  - BACKGROUND: In 1993, a number of influential bodies reported the results of
      consensus conferences on the management of hypertension, including the World
      Health Organization/International Society of Hypertension, the fifth United
      States Joint National Committee (JNC-V), the British Hypertension Society, the
      Canadian Hypertension Society (CHS) and the New Zealand National Advisory
      Committee. Most of these guidelines were in general agreement. The most
      significant difference was in the choice of first-line agents, whether to use
      only beta-blockers or thiazides (JNC-V/CHS) or to use any of the five major
      classes of antihypertensive agents. EVIDENCE FROM THE SHANGHAL TRIAL OF
      NIFEDIPINE IN THE ELDERLY (STONE): At present, this is the only placebo
      controlled trial on newer classes of medications for which results are available.
      The trial has both strengths and weaknesses. Among the strengths of this trial is
      the comparability of the subjects in both arms and the robustness of the results.
      STONE does at least suggest that outcomes with newer agents like long-acting
      nifedipine are comparable to outcomes in major clinical trials in the elderly
      using diuretics and beta-blockers.

PMID- 8986938
TI  - Benefits of twenty-four-hour blood pressure control.
AB  - BACKGROUND: Despite the clear recognition that blood pressure does not remain at
      the same level over a 24-h period, normally falling during sleep and rising
      during times of physical or mental activity, a single blood pressure measurement
      gained during the working day is conventionally used to classify a patient as
      normotensive or hypertensive. ANTIHYPERTENSIVE TREATMENT AND 24-H BLOOD PRESSURE
      CONTROL: There is still no definitive proof that antihypertensive drugs providing
      full 24-h blood pressure control will lead to improved outcomes compared with
      drugs that provide incomplete 24-h blood pressure control. However, there is a
      large body of evidence showing that cardiovascular target-organ damage is
      correlated with 24-h blood pressure measurements and supportive evidence that a
      fall in these 24-h measurements can predict a likely reduction in cardiovascular
      target-organ damage. CONCLUSIONS: In deciding which antihypertensive agent to
      use, physicians should select, where possible, those agents that provide blood
      pressure control through the 24-h period.

PMID- 8986939
TI  - Renal protection in diabetes: an emerging role for calcium antagonists.
AB  - BACKGROUND: The combination of diabetes and hypertension increases the chances of
      progressive renal disorder and, ultimately, renal failure. Roughly 40% of all
      diabetics, whether insulin-dependent or not, develop diabetic nephropathy.
      Diabetic nephropathy is the single most important cause of end-stage renal
      disease in the Western world and accounts for more than a quarter of all end
      stage renal diseases. Diabetic nephropathy is a major cause of increased
      morbidity and mortality in diabetic patients. Increased arterial blood pressure
      is an early and common phenomenon in incipient and overt diabetic nephropathy.
      The relationship between arterial blood pressure and diabetic nephropathy is a
      complex one, with diabetic nephropathy increasing blood pressure and blood
      pressure accelerating the course of nephropathy. OVERVIEW: Calcium antagonists
      antagonize preglomerular vasoconstriction. Additional putative mechanisms include
      the ability to retard renal growth and possibly to attenuate mesangial entrapment
      of macromolecules, and to attenuate the mitogenic effect of diverse growth
      factors. Calcium antagonists (except the original short-acting dihydropyridine
      drugs) reduce microalbuminuria and preserve kidney function in diabetic patients
      with incipient diabetic nephropathy. There are still no long-term trials using
      the new long-acting dihydropyridine calcium antagonists to treat patients with
      incipient nephropathy. A recent, 1-year, randomized, double-blind study in
      hypertensive insulin-dependent diabetic patients with diabetic nephropathy showed
      a better attenuation of the rate of decline in glomerular filtration in patients
      treated with nisoldipine (long-acting dihydropyridine) than with an angiotension
      converting enzyme (ACE) inhibitor. The mean 24-h arterial blood pressure during
      this study was almost identical in both treatment groups, at 103 (SD 9) and 101
      (SD 11) mmHg, respectively. Furthermore, a recent 5-year randomized open study in
      hypertensive non-insulin-dependent patients with diabetic nephropathy has
      revealed the same beneficial effect of a calcium antagonist and of ACE inhibition
      on the progression of nephropathy. In a third group treated with sympatholytic
      drugs, creatinine levels doubled in more than 50% of the subjects compared to
      less than 10% in the two other groups mentioned above. However, long-term studies
      are needed to consolidate these findings and expand them to insulin-dependent
      diabetic patients with diabetic kidney disease.

PMID- 8986940
TI  - Modulation of endothelial function: strategy for long-term cardiovascular
      protection.
AB  - PROPERTIES OF THE ENDOTHELIUM: The endothelium lines all vessels of the body and
      is the most important communication structure between flowing blood on one hand
      and the vessel wall, composed of smooth muscle cells and matrix proteins, on the
      other. Endothelial cells release factors that affect the differentiation and
      growth of vascular smooth muscle cells; dedifferentiation and subsequent
      proliferation of vascular smooth muscle cells are important early mechanisms in
      the pathogenesis of chronic vascular disease. CALCIUM ANTAGONISTS AND THE
      ENDOTHELIUM: Calcium antagonists primarily affect the cellular interactions of
      endothelial cells, smooth muscle cells, monocytes and thrombocytes, which are
      important in the early phases of the development of atherosclerosis. The
      protective effect of calcium antagonists on the vascular system appears to be low
      at later stages, which include increased matrix formation and central necrosis of
      atherosclerotic plaques. CONCLUSION: Present evidence indicates that calcium
      antagonists may be useful prophylactic agents at an early stage in the
      development of atherosclerotic vascular changes.

PMID- 8986941
TI  - Benefit versus risk of calcium antagonists in hypertensive patients with
      concomitant risk factors.
AB  - BLOOD PRESSURE REDUCTION AND CARDIOVASCULAR MORBIDITY AND MORTALITY: Several
      hypertension trials have shown that antihypertensive treatment can reduce the
      cardiovascular morbidity and mortality accompanying this condition. They have
      also shown, however, that the reduction does not entirely normalize the risk of
      hypertensive patients. STRATEGIES TO IMPROVE THE BENEFIT OF ANTIHYPERTENSIVE
      TREATMENT: Although some of the risk of the hypertensive patient may prove to be
      irreversible, pathophysiological and clinical evidence obtained in recent years
      suggests that some modifications to antihypertensive treatment strategies might
      increase the benefit. For example, greater use of drugs such as calcium
      antagonists and angiotensin converting enzyme (ACE) inhibitors as first-line
      agents might bring greater benefits, because some properties of these drugs which
      are additive to their blood pressure lowering effects, such as regression of
      cardiovascular structural changes, nephroprotection and delay of atherogenesis,
      may provide a degree of protection against target-organ damage. ONGOING CLINICAL
      TRIALS AND THE INTERNATIONAL NIFEDIPINE (GITS) GASTROINTESTINAL SYSTEM STUDY OF
      INTERVENTION AS A GOAL IN HYPERTENSIVE TREATMENT (INSIGHT): Several ongoing
      clinical trials are aimed at comparing the effects of calcium antagonists and ACE
      inhibitors versus beta-blockers and diuretics on cardiovascular morbidity and
      mortality. INSIGHT is particularly interesting because the effects of nifedipine
      GITS and a combined thiazide and potassium-sparing diuretic on cardiovascular
      morbidity and fatal events are being compared in patients with hypertension plus
      one or more additional risk factors, such as hypercholesterolemia, smoking,
      diabetes, left ventricular hypertrophy, etc. INSIGHT is therefore the first trial
      to address, in a prospective fashion, the prognostic influence of
      antihypertensive treatment in hypertensives with concomitant risk factors.

PMID- 8986942
TI  - Antibody responses to the hepatitis C virus E2 protein: relationship to viraemia
      and prevalence in anti-HCV seronegative subjects.
AB  - A small proportion of patients with chronic hepatitis C virus (HCV) infection
      show no serological responses to the HCV polypeptides incorporated in commercial
      III generation immunoassays. To determine whether sera from these subjects
      contain antibodies to the highly immunoreactive second envelope polypeptide E2,
      which is not included in current anti-HCV assays, we studied 59 anti-HCV negative
      subjects who were found consistently to be HCV RNA positive by polymerase chain
      reaction (PCR). Controls included 167 anti-HCV seropositive patients with or
      without serum HCV RNA and normal subjects. Antibodies to the E2 region were
      sought for by ELISA using the following antigens: a full length E2 protein
      expressed in insect cells using a baculovirus vector and extracted under
      denaturing conditions (dE2), and a C-terminal truncated soluble E2 (sE2) protein
      (a.a. 390-683), also expressed with a baculovirus vector, containing a signal
      peptide of rabies virus G protein which allows its secretion into the culture
      supernatant. Sera from only two (3.4%) of the 59 anti-HCV negative, HCV RNA
      positive patients recognised sE2 and none dE2. In sharp contrast, 82% of
      seropositive, viraemic patients recognised sE2 and 60% dE2, the difference in
      immunoreactivity being statistically significant (P < 0.0003). A significantly
      lower proportion of sera from anti-HCV positive, HCV RNA negative subjects
      recognised either sE2 or dE2 (16% and 13%, respectively, P < 0.000001). Healthy
      controls were consistently negative. These results indicate that antibody
      responses to predominantly conformational epitopes on the HCV E2 protein are
      common in patients with chronic HCV infection and are strictly related to the
      presence of circulating viral genomes. In contrast, only a minor proportion of
      HCV RNA positive patients, but anti-HCV seronegative by commercial immunoassays,
      have humoral immune responses to the HCV E2 region.

PMID- 8986943
TI  - Heterogeneous response for a mammalian hepadnavirus infection to acyclovir: drug
      arrested intermediates of minus-strand viral DNA synthesis are enveloped and
      secreted from infected cells as virion-like particles.
AB  - Three woodchucks infected persistently with the woodchuck hepatitis virus (WHV)
      were treated with acyclovir (ACV) to investigate the effect of inhibiting viral
      DNA synthesis upon the replication of an orthohepadnavirus in vivo. Normal
      viraemia was reduced during the treatment period in all three animals, but each
      responded with a distinct serum phenotype. In the most provocative case, the
      profile of the WHV DNAs in both the liver and serum provided a simple and novel
      description of the orthohepadnaviral infection for this ACV protocol. The pre
      drug viraemia was rapidly cleared from the serum and replaced by virion-like
      particles containing predominantly minus-strand WHV DNAs. These serum DNA species
      had the character of replicative intermediates arrested in their elongation by
      ACV-mediated chain termination and were contained in particles with a buoyant
      density in CsCl essentially identical with virions. However, in infected
      hepatocytes, initiation of reverse transcription within newly formed core
      particles was not inhibited by the ACV treatment. Instead, an heterogeneous array
      of minus-strand DNAs were synthesised, each presumed to be truncated by the
      incorporation of one molecule of ACV monophosphate. An approximately normal level
      of core particles was present in the liver of this woodchuck after 26 days of the
      ACV protocol; excess drug-arrested nucleocapsids were steadily removed throughout
      the dosing period upon their envelopment and secretion as virion-like particles
      into the circulation. These data suggest that plus-strand DNA synthesis may not
      be absolutely required prior to secretion of virus from the infected cell.

PMID- 8986944
TI  - A randomized controlled trial of high-dose maintenance interferon therapy in
      chronic hepatitis C.
AB  - In chronic hepatitis C virus (HCV) infection, the rate of sustained response to
      interferon is low. We evaluated, in patients responding to a 26-week course of
      interferon, the effect of high-dose maintenance therapy in preventing relapse.
      Three hundred and ten patients with chronic HCV infection (38.3% with cirrhosis,
      80.6% with HCV type 1) received interferon alfa-2b for 26 weeks (10 MU tiw for 8
      weeks, then 5 MU tiw for 18 weeks). One hundred and twenty-four subjects (40%)
      normalized aminotransferases, and were allocated randomly either to continue on 5
      MU tiw for a further 26 weeks (prolonged therapy group: 60 patients) or to stop
      interferon (brief therapy group: 64 patients). Fifty-two weeks after stopping
      interferon the overall sustained biochemical response rate was 13.2% (41/310).
      The number of patients with normal aminotransferases was comparable between the
      prolonged and brief therapy groups (30% vs. 35.9%, P = n.s.), and the rate of HCV
      RNA clearance was similar (48.8% vs. 42.4%, P = n.s.). The timing of
      posttreatment relapse was not influenced by the duration of therapy. Fifty-nine
      patients (19%) did not complete therapy due to adverse effects. Multivariate
      analysis identified four features predicting sustained biochemical response in
      subjects normalizing aminotransferases under therapy: negative HCV-RNA at end of
      therapy, normal aminotransferases at 4 weeks of therapy, high baseline
      aminotransferases, and high baseline platelets. Infection with HCV type 1 was not
      a significant predictor of response, due to its high prevalence in our population
      (80.6%). It is concluded that in patients with chronic hepatitis C mostly
      infected by HCV type 1, a prolonged high-dose interferon course (900 MU over 52
      weeks) did not increase the rate of sustained biochemical response and of HCV-RNA
      clearance in comparison to a brief course (510 MU over 26 weeks).

PMID- 8986945
TI  - Molecular subtyping of human T-lymphotropic virus type I (HTLV-I) by a nested
      polymerase chain reaction-restriction fragment length polymorphism analysis of
      the envelope gene: two distinct lineages of HTLV-I in Taiwan.
AB  - The major type of human T-lymphotropic virus type I (HTLV-I), generally referred
      to as the cosmopolitan type, has been grouped into three subtypes (A, B, and C)
      by phylogenetic analysis of the long terminal repeat sequences of the viral
      genome. Twelve subtype-specific nucleotide variations have been deduced by
      comparison between the envelope (env) sequences of 16 HTLV-I strains with defined
      subtypes and 9 Taiwanese HTLV-I strains. To gain further insights into the
      molecular epidemiology of HTLV-I and the origin of this virus in Taiwan, a rapid
      method of identification for the cosmopolitan subtypes was developed by using a
      nested polymerase chain reaction (PCR) and subsequent restriction fragment length
      polymorphism (RFLP) studies using the two subtype B-specific and four subtype C
      specific nucleotides located within the positions 5708 to 6320 of the envgene.
      The nested PCR-RFLP method was used to subtype HTLV-I from four virus-positive
      cell lines derived from 1 Japanese and 3 North American patients, as well as 41
      blood-unrelated Taiwan Chinese. The sequences of PCR products were determined and
      the six positions of subtype-specific nucleotide variations were examined. The
      sequence data completely supported the subtyping data via the nested PCR-RFLP
      method. The results demonstrated that, as is the case in Japan, at least two
      distinct cosmopolitan subtypes (A and B) of HTLV-I were present in Taiwan, but
      the more prevalent subtype in Taiwan is A in contrast to subtype B in Japan.
      Furthermore, rapid subtyping could facilitate molecular epidemiological studies
      of HTLV-I infection and linkage between HTLV-I subtypes and virus-associated
      diseases.

PMID- 8986946
TI  - Seroepidemiological study of measles after the 1992 nationwide MMR revaccination
      program in Taiwan.
AB  - The incidence of measles declined rapidly in Taiwan after the introduction of the
      measles vaccine into the routine immunization schedule in 1978. However, an
      epidemic still occurred every 3-5 years until recently. A nationwide measles
      mumps-rubella (MMR) revaccination program for school and preschool children has
      been in place since 1992 to control the indigenous transmission of measles. In
      order to understand the current immune status after this recent nationwide
      revaccination program, we determined the presence of measles IgG antibodies by
      enzyme-linked immunosorbent assay (ELISA) in 1,281 blood samples from healthy
      persons aged from 2 months to above 30 years collected between 1993 and 1995, and
      also in another batch of 90 sera samples from children aged 2 years collected
      before 1992. The results showed that 1) the measles antibody seropositive rate
      (36.4%) was lowest in children aged 5-7 months and rose to an unexpectedly high
      level of 85.8% at the age of 12-14 months, 2) the seropositive rate rose further
      to between 85.9% and 95.1% after 2 years of age and remained high in adults and
      pregnant women, and 3) the seropositive rate of the 2-year-old children collected
      before 1992 was 61.4%, which was significantly lower than the rate of the same
      age group collected after the nationwide MMR revaccination program. We conclude
      that the national revaccination program has promoted effectively measles immunity
      in Taiwan. This immunity explains the rarity of reported measles cases since the
      last epidemic in 1989. This revaccination program should continue and be extended
      to all preschool children and young adults so that indigenous measles can be
      eliminated by the year 2000.

PMID- 8986947
TI  - Hepatitis C virus genotypes in French haemophiliacs: kinetics and reappraisal of
      mixed infections.
AB  - The distribution and kinetics of hepatitis C virus (HCV) genotypes and the
      prevalence of mixed infections were studied in a group of 45 French patients with
      haemophilia A or B or von Willebrand's disease, 21 of them being anti-human
      immunodeficiency virus (HIV) positive; genotyping was carried out by three
      methods based on the core, 5' untranslated region (5'UTR), and the detection of
      type-specific NS4 antibodies. Genotyping of the 5'UTR revealed genotypes 1a (n =
      10), 1b (n = 13), 2a (n = 3), 2b (n = 4), 2NC (n = 3), 3a (n = 10), and two mixed
      infections (1a + 1b and 3a + 2). Five of 33 patients showed a change from one HCV
      genotype to another. The core genotyping assay showed 8 of 45 mixed infections:
      6/8 1a + 1b and 2/8 3a + 2. Sequencing of core polymerase chain reaction (PCR)
      products showed that mixed infection 1a + 1b could be explained by nonspecific
      annealing of the 1b primer to type 1a sequence. By designing new primers whose
      sequence was more specific to HCV types 1a and 1b, we could confirm 1a + 1b mixed
      infection in only one of six cases. Serotyping assay showed for 17 of 21 anti-HIV
      negative patients a concordance with the 5'UTR genotype; however, only 6 of 19
      anti-HIV positive patients showed detectable serological reactivity. In summary,
      we have observed a similar HCV genotype distribution between our haemophilic
      group and the French anti-HCV positive patients. The study demonstrates the
      difficulties of assessing with the presently available genotyping and serotyping
      assays the real prevalence of mixed infections in multiply transfused patients.

PMID- 8986948
TI  - Comparison between vaginal tampon and cervicovaginal lavage specimen collection
      for detection of human papillomavirus DNA by the polymerase chain reaction. The
      Canadian Women's HIV Study Group.
AB  - The aim of the study was to compare the accuracy of self-administered vaginal
      tampon (VT) specimens for the detection of human papillomaviruses (HPVs) with
      that of cervicovaginal lavage specimens (CVL). Two hundred seventy-four paired VT
      and CVL specimens were collected prospectively from women at risk of sexually
      transmitted diseases. Specimens were treated and amplified with the polymerase
      chain reaction (PCR). Each woman served as her own control. One hundred and forty
      four of 272 (52.9%) CVLs and 159 of 271 (58.7%) VTs contained HPV DNA sequences
      (correlation of 88%). The sensitivity and specificity of vaginal tampons reached
      93.9% (138/147) and 80.5% (99/123), respectively. HPV typing results were
      concordant for 99 negative paired samples and 114 paired samples positive for the
      same type(s) (correlation of 78.9%). It is concluded that these sampling methods
      collect cells from different areas of the genital epithelium, highlighting the
      importance of further assessment of the comparative predictive value of HPV
      detection in each sample.

PMID- 8986949
TI  - Additional mutations detected in sequential HIV-1 isolates from ZDV-treated
      patients.
AB  - Sequential isolates from four patients under zidovudine (ZDV) therapy were
      obtained using PBMC coculture in the absence or in the presence of 0.25 microM
      ZDV. PBMC-based HIV susceptibility assay demonstrated the emergence of ZDV
      resistance in the sequential isolates from the four patients. Except in one case,
      the isolates obtained in the presence of ZDV did not exhibit a greater resistance
      pattern than their counterparts obtained in the absence of the drug. In parallel,
      partial reverse transcriptase gene sequence was determined directly on amplified
      products from proviral DNA. In addition to the mutations previously described at
      the critical codons 41, 67, 70, 215, and 219, numerous additional mutations were
      found in either ZDV-sensitive or ZDV-resistant isolates. The mutation Thr215Tyr
      was not observed in a case of highly resistant virus (ZDV IC50 > 6.25 microM),
      while the mutation Lys70Arg was found in either resistant or sensitive ones. The
      analysis of additional mutations did not reveal any clear pattern for ZDV
      resistance but pointed out the existence of highly variable regions neighbouring
      the five critical codons. Neither nucleotide sequence nor PBMC-based
      susceptibility assay provided unambiguous data about pretherapy isolates or early
      on-therapy isolates which could predict the emergence of ZDV resistance in
      further samples.

PMID- 8986950
TI  - Improved methods for quantification of human immunodeficiency virus type 1 RNA
      and hepatitis C virus RNA in blood using spin column technology and
      chemiluminescent assays of PCR products.
AB  - The quantification of human immunodeficiency virus type 1 (HIV-1) RNA or
      hepatitis C virus (HCV) RNA has been facilitated by adapting a spin column
      procedure for sample preparation and the use of chemiluminescent detection of
      polymerase chain reaction (PCR) products in microtiter plate format. All
      materials were commercially available and relatively inexpensive. By making a
      single dilution prior to amplification, concentrations of 500 copies to 2.5
      million HIV-1 1 RNA copies per mL and 1,000 copies to 50 million HCV RNA copies
      per mL could be determined on 140-microL samples. Between-run imprecision
      employing the improved procedure for HIV-1 RNA was 23%. Correlation of HIV-1 RNA
      concentrations obtained using chemiluminescent detection with values obtained by
      colorimetric assay of PCR products was 0.98. Correlation of HCV RNA concentration
      determined by the spin column-chemiluminescent assay procedure with those
      obtained by branched DNA methodology was 0.91. Spin columns could be used with
      serum or plasma containing acid-citrate-dextrose or heparin anticoagulant, but
      heparinized samples required treatment with heparinase prior to amplification.

PMID- 8986951
TI  - Acute sporadic hepatitis in the Republic of Yemen.
AB  - The causes of acute icteric viral hepatitis were determined in 78 adult Yemeni
      patients. Acute hepatitis B (IgM anti-HBc positive) was the most common type
      (26.9%). Acute hepatitis E (IgM anti-HEV positive) occurred in 14% and was not
      associated with travel outside Yemen. Sixty percent of all 78 patients were
      positive for IgG anti-HEV as were 40% of a series of 48 healthy male blood donors
      and pregnant females, indicating that HEV is prevalent in Yemen. Acute hepatitis
      A (IgM anti-HAV positive) and hepatitis C and D were responsible for 5.1%, 6.4%,
      and 2.6% cases, respectively. This totals to 106%, as an infection with two
      viruses occurred in 6.4% cases. In 51.3% of all cases, no virological markers of
      acute hepatitis were detected, suggesting an as yet undiscovered agent.

PMID- 8986952
TI  - Reactivity of synthetic peptides representing selected sections of hepatitis C
      virus core and envelope proteins with a panel of hepatitis C virus-seropositive
      human plasma.
AB  - A series of 54 synthetic peptides, 15-20 residues long, that represented selected
      parts of the structural proteins of hepatitis C virus (HCV) were tested for
      immunoreactivity with a panel of 45 plasma samples from potential blood donors
      who were known to be seropositive for anti-HCV. Most of the ten peptides that
      represented the core protein showed reactivity with most of the panel samples.
      All except one of the 20 peptides that represented non-hypervariable regions of
      envelope proteins E1 and E2 showed little or no reactivity. In contrast, 18 of
      the the 24 peptides that represented variants of the hypervariable region 1 of
      the E2 protein reacted with at least one panel sample. Notably, 40% of the panel
      samples cross-reacted with two or more different peptides sequences some of which
      differed by more than 50%. Two panel samples each cross-reacted with seven
      different peptide sequences. The results suggest a broad anti-hypervariable
      region antibody specificity in many anti-HCV-seropositive samples and possible
      limits on the mutability of hypervariable region sequences. The work contributes
      to understanding the immunogenicity and persistence of HCV.

PMID- 8986954
TI  - Spock would have been a terrible nurse (and other issues related to critical
      thinking in nursing)

PMID- 8986953
TI  - Temporary seronegativity in a human immunodeficiency virus type 1-infected man.
AB  - Over a period of 3 months a human immunodeficiency virus 1 (HIV-1)-infected
      patient showed a sequence of positive-negative-positive anti-HIV screening test
      results. During this period the level of HIV p24 antigen declined and the HIV
      antibody pattern by Western blot gradually became complete, suggesting recent HIV
      infection. However the patient's weight loss, esophageal candidiasis, and
      Pneumocystis carinii pneumonia, together with the severely and persistently
      lowered CD4 cell counts and the absence of an IgM anti-HIV response, suggest late
      stage HIV infection. Despite additional and follow-up testing, it was impossible
      to determine whether the patient suffered from acute, primary HIV infection with
      severe immunodepression or from advanced HIV infection (AIDS) with hampered HIV
      antibody production leading to false-negative test results by the anti-HIV enzyme
      immunoassay and Western blot. This case illustrates that HIV serology does not
      always follow the rules. The presence of HIV infection should be considered in a
      patient showing clinical signs of acute or late-stage HIV infection, even if the
      anti-HIV assay is negative.

PMID- 8986955
TI  - Critical thinking: prevailing practice in baccalaureate schools of nursing.
AB  - This study describes the prevailing practice of NLN-accredited baccalaureate
      nursing programs with respect to the NLN-required outcome criterion of critical
      thinking. Currently accredited 4-year baccalaureate nursing programs scheduled
      for an accreditation site visit in the 1992 to 1993 and 1993 to 1994 academic
      years were invited to participate by providing a copy of the self-study report
      pages relevant to NLN Required Outcome Criterion 1: Critical Thinking. Of the 124
      programs in the population, 55 used the newly approved accreditation criteria and
      provided the requested materials. This article describes the prevailing practices
      regarding the definition and evaluation/measurement of critical thinking.

PMID- 8986956
TI  - Critical thinking of beginning baccalaureate nursing students during the first
      clinical nursing course.
AB  - The development of critical thinking is an essential component of baccalaureate
      nursing education and yet little is known about beginning nursing students'
      critical thinking abilities in making clinical decisions. The purpose of this
      study was to describe the critical thinking of seven beginning baccalaureate
      nursing students during their first clinical nursing course. Qualitative
      methodology using the case study approach was used to describe students' critical
      thinking from their perspectives. Sources of data for describing students'
      critical thinking included reflective journal writing, interviews, and the
      researcher's nonparticipatory lab observations. Paul's (1993) dimensions of
      reasoning were used as a framework to describe students' critical thinking. Four
      major themes revealed through the data analysis were: development of the
      professional self-perspective, development of a perfectionist perspective,
      development of a caring perspective, and development of a self-directed learning
      perspective. The descriptive nature of the study indicated that beginning
      students do indeed think critically. Opportunities for dialogue in a supportive
      environment are instrumental in facilitating students' critical thinking and
      growth as reflective practitioners.

PMID- 8986957
TI  - An approach to defining and operationalizing critical thinking.
AB  - The faculty in a midwestern university confronted the imperative to define and
      measure critical thinking in the nursing undergraduate curriculum. Theoretical
      and operational definitions were developed by faculty through literature review,
      extensive discussion, student participation, and evaluation. These activities
      also led to the generation of a list of indicators to assess the presence of
      critical thinking. Through the process faculty have developed a deeper
      understanding of critical thinking and fostered students' critical thinking
      abilities.

PMID- 8986958
TI  - Critical thinking: a model.
AB  - The emphasis on critical thinking in nursing has increased in response to the
      rapidly changing health care environment. This emphasis is underscored in nursing
      education by the National League for Nursing (NLN) accreditation process with the
      inclusion of a required outcome criterion related to the critical thinking
      abilities of baccalaureate nursing graduates. This article proposes a model and
      an accompanying process that can provide direction for nurse educators in the
      development and evaluation of nursing students' critical thinking abilities.

PMID- 8986959
TI  - Promoting the cognitive development of freshman nursing students.
AB  - One of the goals of baccalaureate nursing education is to facilitate students'
      cognitive development, that is, their ability to employ reason, manage diversity,
      and engage in contextual decision-making. Despite this goal, however, studies
      indicate that the majority of nursing students tend to be at the lower levels of
      development, rather than at more advanced levels. The purpose of the study
      reported here was to describe the cognitive development of one university's
      nursing student population at the beginning and end of the freshman year,
      investigate the effects of planned developmental instruction strategies on
      cognitive growth, and investigate the relationship among cognitive development,
      GPA, and SAT scores. While subjects evidenced some cognitive growth, the mean
      level of cognitive development for all subjects was at the lower end of the
      scale. Specific instructional strategies are described, statistical and
      qualitative analyses of groups are reported, and suggestions for further research
      are proposed.

PMID- 8986960
TI  - Use of Iliad to improve diagnostic performance of nurse practitioner students.
AB  - Nurse practitioners (NPs) have dual goals as primary care providers, combining
      the traditional goals of nursing with extended goals as diagnosticians.
      Diagnostic reasoning, therefore, is a critical component of NP education. Iliad,
      a computerized diagnostic reasoning expert system, has been used effectively to
      teach diagnostic skills to medical students. A pilot study was undertaken to
      determine the effects of Iliad training on NP students' diagnostic skill
      performance and to identify technical and instructional issues of implementation.
      The study found that the use of Iliad improved NP students' diagnostic reasoning,
      and that the training effects were modified by prior nursing experience.
      Successful use of Iliad required planning, faculty commitment, and technical
      support.

PMID- 8986961
TI  - A comparison of critical thinking abilities between accelerated and traditional
      baccalaureate nursing students.
AB  - Critical thinking is an outcome expected of all nursing graduates. The purpose of
      this study was to evaluate the influence of an accelerated nursing curriculum on
      students' abilities to think critically. The Watson-Glaser Critical Thinking
      Appraisal (WGCTA) was used to measure the critical thinking ability of the
      student nurses. The sample consisted of two groups of BSN students: traditional
      (n = 45) and accelerated (n = 43). Both groups completed the WGCTA at the
      beginning and end of their nursing course sequence. Findings revealed a
      significant difference between the test scores of the two group at the beginning
      of the curriculum (t = -2.42) but no significant difference at the end (t = 
      1.76). Findings also revealed significant differences in pre- and post-curriculum
      test scores of traditional students (t = -2.84) but no difference for accelerated
      students (t = -1.65). Findings have implications for BSN program development.

PMID- 8986962
TI  - Oral manifestations associated with human immunodeficiency virus infection in a
      Spanish population.
AB  - A study was made of the oral manifestations in 396 patients with human
      immunodeficiency virus (HIV) infection. The following risk groups were
      established: intravenous drug users (79.5%), homosexuals (7.8%), homosexual
      intravenous drug users (3.3%), heterosexuals (8.1%) and hemophiliacs/transfusion
      patients (1.3%). The oral lesions, in decreasing order of frequency, were:
      periodontal disease (78.28%), candidiasis (65.65%), hairy leukoplakia (16.16%),
      herpes simplex virus lesions (5.30%). Kaposi's sarcoma (2.27%), recurrent
      aphthous ulceration (RAS) (1.01%), lichen planus (0.5%), non-Hodgkin's lymphoma
      (0.25%), tuberculous lesion of the tongue (0.25%) and ulcerations of uncertain
      etiology (0.25%). Attention is drawn to the greater predominance of these lesions
      in patients with CD4 values of less than 200/ mm3, compared with those who have
      higher lymphocyte counts.

PMID- 8986963
TI  - Hepatitis C virus infection in Italian patients with oral lichen planus: a
      prospective case-control study.
AB  - To assess the aetiology of liver disease associated with lichen planus, we
      prospectively studied 70 consecutive newly diagnosed patients with oral lichen
      planus (OLP) living in northwest Italy (Piemonte) and 70 controls matched for age
      and sex with other oral keratoses coming from the same district. Twenty-two
      patients with OLP (31.4%) and 9 controls (12.9%) were found to be affected by
      chronic liver disease (CLD) (P = 0.014). In sixteen of the 22 OLP patients with
      CLD the liver disease was hepatitis C virus (HCV)-related, whereas 2 of the 9
      controls had a HCV-related CLD (P = 0.016). In another OLP case, liver damage was
      related to a combination of HCV and alcohol abuse. The prevalence of HCV
      antibodies in the whole OLP group (27.1%) was significantly higher than in
      controls (4.3%) (P = 0.014), whereas no difference was found between the OLP and
      control groups regarding hepatitis B virus markers and other common causes of
      CLD. HCV infection was more frequently found in patients with erosive OLP (58.8%)
      than in patients with non-erosive OLP (13.2%) (P = 0.004). Serum HCV-RNA was
      detected by polymerase chain reaction (RT-PCR) in the majority (93.7%) of OLP
      patients who had HCV antibodies. Excluding OLP and control patients with HCV
      markers, there was no difference between the two groups regarding frequency of
      CLD. Our data show that HCV is probably the main pathogenic factor in liver
      disease of Italian patients with OLP, and suggests that HCV could be involved in
      the pathogenesis of OLP.

PMID- 8986964
TI  - T cell antigen receptor expression by intra-epithelial lymphocytes in oral lichen
      planus.
AB  - The distribution of T lymphocytes expressing the alpha beta or gamma delta
      heterodimer of the T cell receptor (TCR) was examined in normal oral mucosa (NOM)
      and reticular oral lichen planus (OLP) using a panel of antibodies specific for
      CD3, the alpha beta TCR and the gamma delta TCR. Intra-epithelial lymphocytes
      were counted and epithelial surface length was measured by image analysis. T
      cells in the lamina propria were not quantified. Total intra-epithelial
      lymphocytes were increased in OLP compared with NOM (P = 0.0004). The proportions
      of cells expressing the gamma delta TCR in NOM and OLP were 10% and 9.3%,
      respectively, suggesting there is no selective recruitment from the circulation
      of either alpha beta or gamma delta TCR-bearing cells into normal oral epithelium
      or that affected by OLP. The role, if any, of gamma delta T cells in the
      pathogenesis of OLP remains to be determined.

PMID- 8986965
TI  - Immunoglobulin G subclass measurements in recurrent aphthous stomatitis.
AB  - We have measured serum levels of IgG subclasses and total IgG, IgA and IgM in a
      group of 34 recurrent aphthous stomatitis (RAS) patients. At the time of blood
      collection, 23 of the 34 patients had active oral lesions. The remaining 11
      patients were at an inactive stage. All measurement were performed in the
      Beckmann 360 Array Protein System. Serum levels of IgG2 subclass were
      significantly lower (P < 0.05) in the whole group of patients (34) when compared
      to the control group. This relationship was still significant (P < 0.05) when
      only the 11 patients without active oral lesions were considered but disappeared
      in patients at an active stage. We conclude that low serum levels of IgG2 may
      play a role in the pathogenesis of RAS, just as in other recurrent infectious
      diseases, and that serum levels of this immunoglobulin subclass, as well as total
      IgA, may undergo transient changes, depending on the different periods of
      activity and quiescence of the disease.

PMID- 8986966
TI  - MTS1 gene mutations in archival oral squamous cell carcinomas.
AB  - Multiple tumor suppressor gene 1 (MTS1) has been found mutated or deleted in a
      variety of human cancers. Our purpose was to identify and characterize MTS1 gene
      mutations in primary oral squamous cell carcinomas (SCCs) in each of the three
      exons of the MTS1 gene. Seventeen archival samples of oral SCC were evaluated for
      the presence of MTS1 mutations using single strand conformation polymorphism
      (SSCP) and DNA sequencing. Three of 17 tumors exhibited MTS1 gene mutations: one
      tumor exhibited a mutation in exon 2 and two tumors exhibited mutations at the
      splice site junction of intron 2 and exon 3. Three tumors also exhibited a common
      base change in the 3' untranslated region of exon 3, which is interpreted as a
      likely polymorphic variant. An examination of the three tumors exhibiting MTS1
      point mutations revealed no unique characteristics relative to p53
      immunohistochemical activity, mitotic frequency, or degree of histologic
      differentiation. This study indicates that MTS1 gene mutations may be involved in
      at least a minor proportion of oral SCCs.

PMID- 8986967
TI  - Immunohistochemical evaluation of the Ca(2+)-binding S-100 proteins S-100A1, S
      100A2, S-100A4, S-100A6 and S-100B in salivary gland tumors.
AB  - The Ca(2+)-binding S-100 proteins are involved in the regulation of a number of
      cellular processes and an altered expression has been reported in several
      neoplastic tissues. Tissue specimens of normal salivary glands (n = 23),
      pleomorphic adenomas (n = 60), basal cell adenomas (n = 6), canalicular ademomas
      (n = 2), myoepitheliomas (n = 2), adenoid cystic carcinomas (n = 26) and
      adenocarcinomas NOS (n = 11) were evaluated for the expression of S-100A1, S
      100A2, A-100A4, S-100A6 and S-100B by using highly specific polyclonal and
      monoclonal antibodies generated against the recombinant human protein. In normal
      salivary glands, the ductal cells showed mild to intense immunoreactivity for S
      100A1, S-100A2, S-100A4 and S-100A6, while S-100B was observed in nerve fibers in
      the connective tissue. The normal myoepithelial cells were unreactive. In
      pleomorphic adenoma, the luminal tumor cells of the duct-like structures showed
      moderate to intense immunoreactivity for S-100A2, while reactivity for S-100A1, S
      100A4 and S-100A6 was relatively weak. The non-luminal cells, also termed
      neoplastic myoepithelial cells, showed immunoreactivity for S-100B, while tumor
      cells in the solid, myxoid and chondroid areas were immunoreactive for S-100A1, S
      100A4, S-100A6 and S-100B. The non-luminally located tumor cells in basal cell
      adenomas and canalicular adenomas, and numerous tumor cells in clusters in
      myoepitheliomas were intensely reactive for S-100A2. In adenoid cystic carcinomas
      and in adenocarcinomas not otherwise specified, the luminal cells forming the
      tubular or cribriform structures were markedly positive for S-100A2 and/or S
      100A6. Squamous metaplastic cells in salivary tumors showed intense
      immunoreactivity for S-100A2. The results of the present study suggest that the
      majority of the tumor cells in salivary neoplasms, despite the most heterogeneous
      tumor cell differentiation, express S-100 proteins more heterogeneously than the
      normal glandular ducts. The salivary ducts in normal glands, the luminal tumor
      cells and squamous metaplastic cells in the neoplastic lesions were intensely
      immunoreactive for S-100A2 as compared to S-100A1, S-100A4 or S-100A6. In
      contrast, the non-luminal tumor cells showed a rather heterogeneous expression of
      the S-100 proteins.

PMID- 8986968
TI  - Central odontogenic fibroma current concepts.
AB  - The author reviews current knowledge concerning the central odontogenic fibroma,
      which at present in incompletely understood, and reaches the following
      conclusions. 1) The separation of this lesion into simple and WHO types remains
      valid because they exhibit different histologic features. However, more care
      should be taken in rendering the diagnosis of the WHO type than in the past;
      unlike the simple type, it is a fibroblastic lesion. 2) Complex central
      odontogenic fibroma is a more appropriate term than the WHO type because the WHO
      does not use the latter term in its 1992 manual. 3) The microscopic distinction
      of simple odontogenic fibroma from desmoplastic fibroma remains difficult in some
      cases. 4) The granular cell odontogenic tumor, which has sometimes been referred
      to as a type of odontogenic fibroma, is a separate entity, although some simple
      odontogenic fibromas exhibit scattered granular cells. 5) The separation of
      lesions that have been reported recently as odontogenic fibromas with giant cell
      reactions from central giant cell granulomas that exhibit foci of odontogenic
      epithelium requires further study.

PMID- 8986969
TI  - Hyalinizing clear cell carcinoma: report of a case.
AB  - Hyalinizing clear cell carcinoma (HCCC) is a recently described low-grade
      malignant neoplasm of minor salivary glands. Of the thirteen reported patients
      with this neoplasm, the majority have occurred in the oral cavity of elderly
      women. We report another case and add further supporting evidence that
      hyalinizing clear cell carcinoma is a distinct pathological entity.

PMID- 8986970
TI  - A comparison of colo-colic and ileo-colic intussusception.
AB  - There are many differences in the clinical features of intussusception between
      African and temperate countries. The records of 192 patients with intussusception
      who presented to the Pediatric Surgical Service at King Edward VIII Hospital,
      Durban, South Africa during a 10-year period were reviewed. Compared with
      temperate countries, the patients were older (median, 1 year 7 months), presented
      later (median, 4.2 days), had a higher proportion of colo-colic lesions (17%),
      had absence of primary bowel pathology, and had a high surgical rate (82%). To
      define clinically important differences, the clinical and pathological features
      of 158 cases of ileo-colic intussusceptions were compared with 34 colo-colic
      cases. Compared with the ileo-colic group, colo-colic lesions occurred in older
      children (median, 3.8 years) (v 1.5 years; P < .001). In the colo-colic group,
      there were fewer shocked and pyrexial patients, and the rate of successful
      nonoperative reduction was higher. The groups had a similar incidence of surgical
      intervention (82%). In the ileo-colic group, there was a higher mortality rate
      and more complications, but only the higher resection rate (P < .001) was
      statistically significant.

PMID- 8986971
TI  - Changing patterns of diagnosis and treatment of infantile hypertrophic pyloric
      stenosis: a clinical audit of 303 patients.
AB  - This review of 303 patients with infantile hypertrophic pyloric stenosis (IHPS)
      concentrates on the influence of clinical audit on diagnosis, complications, and
      factors contributing to hospital stay. Although the audit has enabled improvement
      in care by pediatric surgeons, there has been less change in areas controlled by
      other specialities. During a 12-year period, the number of patients diagnosed
      solely by clinical examination decreased from 74% to 28%, and the use of
      diagnostic tests increased (ultrasonography from 16% to 65% and barium meal from
      12% to 28%). This trend continued throughout the series despite a review after
      8.5 years, which recommended fewer tests. Although there may be some benefit from
      earlier confirmation of IHPS (the percentage of patients with a serum chloride
      value of less than 85 mmol/L decreased from 26% to 15%), the need for diagnostic
      tests could be reduced by expectant management. Better improvement occurred with
      surgical complications; the incidence of mucosal perforation decreased from 7 of
      151 (4.6%) in the first 6 years to 0 of 152 in the last 6 years, and wound
      dehiscence was reduced from 3 to 0. The wound infection rate decreased from 9% to
      4%, but had fluctuations. The average length of stay was reduced from 3.7 to 3.2
      days. Further reductions in hospital stay will depend on earlier operation for
      patients with normal electrolyte values at the time of admission (61%) and a
      preparedness to confidently discharge patients even if there is vomiting. From
      the data available, early operation on the day of admission and discharge the
      next day would be a reasonable strategy for the majority of patients whose
      admission electrolyte values are normal. Complications such as mucosal
      perforation and wound dehiscence should be rare. This is not to suggest that IHPS
      is a condition of minor consequence; the surgeon must be skilled and care
      meticulous. If electrolytes are disturbed at the time of operation or if
      unrecognized mucosal perforation occurs, what should be an uneventful illness can
      result in disaster.

PMID- 8986972
TI  - Comparison of continuous infusion of fentanyl to bolus dosing in neonates after
      surgery.
AB  - OBJECTIVE: Concern about respiratory depression may lead to underuse of
      postoperative narcotic analgesia in neonates. The authors compared continuous
      infusion of fentanyl with bolus dosing in infants after surgery to determine
      whether continuous infusion is associated with less respiratory depression. STUDY
      DESIGN: In the first phase of the study, 16 patients were randomly assigned to
      receive fentanyl by continuous infusion (C) or bolus dosing every 2 hours (B) in
      a double-blinded trial. Respiratory events were recorded. An observational pain
      score and saliva for cortisol concentration were obtained 2, 8, and 24 hours
      after beginning treatment to compare efficacy of pain control. In the second
      phase, 20 additional patients received fentanyl by continuous infusion in an
      unblinded fashion, with the same data collection, to more accurately determine
      the incidence of respiratory events. RESULTS: In phase 1, apnea occurred in eight
      of nine B patients (89%) compared with one of seven C patients (14%; P < .009),
      prompting termination of the randomized trial. The incidence of apnea or
      significant respiratory depression in the next 20 patients (phase 2) who received
      fentanyl by continuous infusion was 25% (5 of 20; P < .01 v B). Episodes of apnea
      in B patients required significantly more intervention than episodes in C
      patients (P < .01). However, in phase 2, more patients remained intubated and
      ventilated than in phase 1. Pain scores and salivary cortisol concentrations
      decreased over the 24-hour study period and were similar in B and C patients
      during both phases of the study. CONCLUSION: Continuous infusion of fentanyl at
      the doses studied is associated with pain control similar to that with bolus
      dosing at regular intervals. Although episodes of respiratory depression were
      less severe and less frequent for C patients, there may be an increased need for
      ventilator support with continuous infusion of fentanyl to achieve acceptable
      pain control. Providing adequate pain control to neonates in the immediate
      postoperative period remains a challenge.

PMID- 8986973
TI  - Abdominal aortic aneurysms in children.
AB  - Abdominal aortic aneurysms are rare in children. Causes include mycotic
      aneurysms, vasculitides (eg, Takayasu's arteritis), connective tissue diseases
      (eg, Marfan's syndrome, Ehlers-Danlos syndrome, and tuberous sclerosis) and
      traumatic false aneurysms. Four cases are described. Case 1 was a 12-year-old boy
      who presented with an acute unheralded rupture of the subdiaphragmatic aorta
      accompanied by lower limb paralysis and ischemia. Attempted repair failed because
      of extensive friability of the large arteries. Histological evaluation confirmed
      cystic medial necrosis despite Marfanoid phenotype. Cases 2 and 3 were boys aged
      12 and 11 with Takayasu's arteritis who presented with hypertensive
      encephalopathy and heart failure. Although both had involvement of the origins of
      the renal arteries, one aneurysm was predominantly suprarenal and the other
      infrarenal. Currently both children are being managed successfully with
      antihypertensive therapy. Case 4 was a 5-year-old girl who presented with
      hypertension and a pulsatile abdominal mass after treatment of infective
      endocarditis 18 months previously. Arteriography and three-dimensional computed
      tomography confirmed an aneurysm (6 x 5 x 4 cm) arising from the aorta and
      involving the right renal artery. Aneurysmectomy, removal of a small ischemic
      right kidney, and Gore-Tex grafting resulted in cure of the hypertension and
      uneventful recovery. The present series confirms that rupture is a fatal
      complication, renovascular complications are common, and medical control of
      hypertension is an essential part of management. Management strategies need to be
      highly individualized, and may be successful without surgical intervention. Close
      clinical and ultrasound follow-up of those managed nonoperatively is essential.

PMID- 8986974
TI  - Diversion of salivary flow to treat drooling in patients with cerebral palsy.
AB  - The authors performed six sialodochoplasties between 1991 and 1994 to treat
      drooling in six children who suffered from cerebral palsy. There were three boys
      and three girls, aged 13 to 22 years (mean, 16 years). All patients underwent
      parotid duct rerouting. The first four patients (group I) also underwent
      associated excision of submandibular ducts, and the last two patients (group II)
      benefited from rerouting of the submandibular ducts. In group I, results were
      considered good in two cases, fair in one case, and poor in one case. A fistula
      of the new Stenon duct appeared in one patient, which required excision and
      ligation followed by progressive involution of the parotid gland. Both group II
      patients had excellent and rapid results. The requirements leading to surgical
      decision are determined. The importance of physiotherapy is emphasized. Surgical
      techniques are described and discussed, as are objective criteria for the
      assessment of surgical results, namely salivary radioisotopic scanning.

PMID- 8986976
TI  - Thoracoscopy in children.
AB  - Pediatric surgical experience with video-assisted thoracoscopy is limited. The
      authors report their experience with 27 thoracoscopies in 22 children. The median
      age was 6.1 years (range, 1 day to 16 years). The two primary indications for
      thoracoscopy were management of pneumothorax and mediastinal cysts. Fifteen
      thoracoscopies accomplished their purpose without complications. Intraoperative
      complications required conversion to an open operation in three patients. One
      bronchogenic cyst and four pneumothoraces recurred. The main complications were
      poor visualization, bleeding from an intercostal artery, and difficulty with
      suturing. Compared with open thoracotomy, anesthesia time did not differ
      significantly, and less pain medication was required postoperatively.

PMID- 8986975
TI  - Can blood gas values predict pulmonary hypoplasia in antenatally diagnosed
      congenital diaphragmatic hernia?
AB  - The prognosis of antenatally diagnosed congenital diaphragmatic hernias (CDH) is
      clearly related to the degree of pulmonary hypoplasia (PH). After birth,
      controversies remain regarding the implementation of various therapies,
      especially the use of extracorporeal membrane oxygenation (ECMO). In the
      literature, the persistence of a Pao2 below 100 mm Hg and of Paco2 above 40 mm Hg
      despite optimal conventional therapy indicates poor prognosis. Therefore, since
      1992, published and personal experiences led the authors to exclude CDH patients
      from ECMO when conventional therapy (including high-frequency oscillatory
      ventilation and nitric oxide) did not obtain Pao2 of above 80 mm Hg and Paco2 of
      below 60 mm Hg. The aim of this retrospective study is to determine whether blood
      gas results correlate with postmortem findings. Between July 1990 and July 1994,
      32 cases of CDH were monitored antenatally and managed postnatally at the
      authors' institution. Six patients survived; 26 died, including one immediately
      at birth. Thirteen were treated by ECMO. Seventeen had a best Pao2 of above 80 mm
      Hg, including the six survivors. Fourteen did not reach this level, and none of
      them survived. Twenty-three infants underwent postmortem examination. PH was
      assessed using two criteria: (1) lung weight to body weight ratio (LW/BW) and (2)
      radial alveolar count (RAC). Two patients did not have hypoplasia (LW/BW >
      0.018). Twenty-one patients had PH; 12 of them had an LW/BW ratio of less than
      .009; for 9, the LW/BW ratio was between .009 and .018, and the RAC (< 3.1)
      confirmed PH. All infants with a best Pao2 of less than 80 mm Hg had PH. Patients
      with a best Pao2 of greater than 80 mm Hg included two infants who died from
      complications without PH, eight infants with demonstrated PH, and the six
      survivors. In conclusion. (1) No infant with nonhypoplastic lungs has been
      deprived of ECMO by the authors' criteria. (2) Adequate values of blood gases may
      not eliminate PH. Therefore, this probably justifies starting ECMO when
      conventional therapy fails. (3) Conversely, permanent poor values of Pao2 allowed
      the prediction of PH in all cases. Such patients probably can be excluded from
      ECMO treatment.

PMID- 8986977
TI  - Routine use of the piggyback technique in pediatric orthotopic liver
      transplantation.
AB  - The theoretical advantages of the piggyback technique over conventional
      orthotopic liver transplantation are as follows. (1) Continuous venous
      decompression during the anhepatic phase is provided without venovenous bypass.
      (2) Warm ischemia time can be shortened because there is no need for the
      infrahepatic vena cava anastomosis. The following report is a review of the
      authors' experience with this method in children during the past year at their
      institution. Analyses of intraoperative hemodynamics and blood loss,
      postoperative renal function, patient and graft survival, and length of hospital
      stay have shown excellent results. There were no intraoperative deaths, and
      causes of death and graft loss were not related to the technique. The authors
      conclude that children who undergo liver transplantation can be very
      satisfactorily managed with the piggyback operation, and this technique may be
      more advantageous than the conventional method.

PMID- 8986978
TI  - The surgical management of giant cervicofacial lymphatic malformations.
AB  - Giant cervicofacial lymphatic malformation, a potentially life-threatening
      congenital malformation, historically has been removed in staged resections.
      However, complete surgical extirpation is desirable and can be achieved with the
      aid of a multidisciplinary team. The authors present the case of a 12-year-old
      girl who had an extensively enlarged cervicofacial lymphatic malformation.
      Effective treatment involved aggressive surgical excision, facilitated by
      mandibular osteotomies to provide access to the floor of the mouth, the tongue,
      and the pharyngeal wall. In addition, total removal of involved facial and neck
      skin was performed. The remaining soft tissue defect was reconstructed primarily
      with an abdominal musculocutaneous free flap. In the 5 years since the procedure,
      there has been no recurrence. Based on this experience, excision of involved skin
      and mandibular access osteotomies are important techniques to help completely
      remove cervicofacial lymphatic malformations with oral involvement, thus
      potentially reducing the number of recurrences. In addition, these cases require
      the best efforts of a multidisciplinary team to achieve a successful result so
      that complete and radical excision can be performed with the hope of avoiding the
      pitfalls of multiple resections.

PMID- 8986979
TI  - Prediction of morbidity during infancy after repair of congenital diaphragmatic
      hernia.
AB  - Recent studies have suggested there may be a high incidence of pulmonary and
      extrapulmonary sequelae among infants who have undergone repair of congenital
      diaphragmatic hernia (CDH). The aim of this study was to identify factors that
      predict high-risk cases to facilitate counseling of parents. Morbidity, defined
      as conditions requiring treatment and/or hospitalization during follow-up, was
      documented. Only five of 15 cases that had been diagnosed antenatally (at 16 to
      26 weeks' gestation) and underwent surgical repair after preoperative
      stabilization were without morbidity at the time of follow-up. Respiratory
      problems were identified in seven (chylothorax in 3, recurrent infections in 4)
      and failure to thrive in four; three infants required further gastrointestinal
      surgery. A comparison of infants with and without morbidity showed that the only
      significant difference between the groups was in the duration of respiratory
      support. A requirement for respiratory support for more than 10 days had 90%
      sensitivity, 100% specificity, and a positive predictive value for morbidity at
      follow-up of 100%.

PMID- 8986980
TI  - Restorative proctocolectomy in children and adolescents.
AB  - Children and adolescents with colitis present specific problems for surgeons.
      There has been a fashion, particularly in North America, for restoring continuity
      after colectomy by a direct ileo-anal anastomosis. The authors reviewed their
      experience with restorative proctocolectomy with ileal reservoir (RPC) in
      patients under 18 years of age to evaluate the outcome and to discuss the
      problems and challenges associated with the procedure in this age group. Fifteen
      patients (6 boys, 9 girls) were operated on between 1984 and 1995. The diagnoses
      included 12 patients with ulcerative colitis (UC), two with familial adenomatous
      polyposis (FAP), and one with total colonic neuronal dysplasia. The median age of
      the patients at the time of ileal pouch formation was 15 years, and follow-up
      data were available for all patients at a median of 43 months. Ten patients with
      UC underwent pouch surgery 4 to 14 months after initial total abdominal colectomy
      (7 for acute severe disease, 3 for chronic disease). Four patients (2 with
      chronic UC, 2 with FAP) underwent primary RPC. There were no deaths in this
      series. Three (20%) patients suffered serious early morbidity (pouch hemorrhage,
      pelvic sepsis, severe psychological crisis). Late morbidity included three
      patients who had small bowel obstruction, one who required laparotomy, two who
      required pouch revision, and five of 12 (42%) patients with UC who presented with
      a documented episode of pouchitis between 2 and 72 months after ileostomy
      closure. All patients had acceptable bowel frequency and quality of continence.
      This experience suggests that RPC provides an important surgical option for
      children and adolescents with UC or FAP.

PMID- 8986981
TI  - Characterization of alpha-adrenoceptor activity in the preterm piglet mesentery.
AB  - To characterize neonatal mesenteric alpha-adrenoceptor populations, an
      extracorporeal perfusion circuit was established to control intestinal blood flow
      in prematurely delivered (by cesarean section at 90% of gestational age) piglets.
      Activation of alpha 1-adrenoceptors was documented by observing dose-dependent
      increases in mesenteric perfusion pressure after intramesenteric arterial
      injection of methoxamine; alpha 2-adrenoceptor activity was confirmed by finding
      similar increases in mesenteric perfusion pressure after intramesenteric arterial
      injections of BHT 933. Peripheral intravenous injections of WB 4101 (a
      competitive alpha 1A-adrenoceptor antagonist), but not clorethylclonidine (CEC,
      an alpha 1B-adrenoceptor antagonist), significantly blunted (P < .05, ANOVA) the
      mesenteric vasoconstrictor responses to methoxamine. The mesenteric
      vasoconstrictor response to BHT 933 (an alpha 2-adrenoceptor agonist) also was
      blunted by WB 4101, but not by CEC. These data suggest that alpha 1A- and alpha 2
      adrenoceptors can be activated in the small intestinal mesentery of piglets well
      before they reach full-term maturation, although receptor specificity has not
      been fully established.

PMID- 8986982
TI  - Epithelioid sarcoma in children.
AB  - Literature regarding the natural history and prognosis of epithelioid sarcoma in
      the pediatric population is sparse. During the past 11 years, eight patients with
      epithelioid sarcoma were treated at St Jude Children's Research Hospital. Of the
      eight children, six of whom were male, seven presented with localized disease and
      one with metastatic disease. The primary tumor was located in the upper extremity
      in four patients; the other sites were the scalp, external ear, back, and
      mediastinum. The mean duration of symptoms before diagnosis was 8.3 months
      (range, 1 to 12 months). Surgical treatment comprising amputation or wide local
      excision was performed in six patients, three of whom had additional lymph node
      dissection. Three patients received multiagent chemotherapy, and four patients
      were treated with supplementary radiation. Two patients died of progressive local
      and distant disease within 9 months of diagnosis. The other six patients are
      alive and have no evidence of disease 12 months to 10 years 6 months after the
      completion of treatment.

PMID- 8986983
TI  - Transdiaphragmatic pressure gradients and the lower esophageal sphincter after
      tight abdominal wall plication in the rat.
AB  - BACKGROUND: Gastroesophageal reflux (GER) is increasingly recognized as a
      complication of surgical closure of gastroschisis and omphalocele. AIM: This
      study tests the hypothesis that forceful abdominal wall closure reinforces the
      transdiaphragmatic pressure gradients that constitute the main GER-driving force
      and challenges the antireflux barrier. MATERIALS AND METHODS: Abdominal and
      esophageal pressures as well as lower esophageal sphincter pressures (LESP) and
      length (LESL) were measured in 17 adult rats before tight abdominal wall
      plication, after it, and 1 week later. RESULTS: This maneuver increased the
      transdiaphragmatic expiratory gradient from 0.67 +/- 1.31 to 6.97 +/- 2.68 mm Hg
      (P < .01) and the inspiratory gradient from 4.36 +/- 1.13 to 10.79 +/- 2.31 mm Hg
      (P < .01) by markedly increasing both the expiratory (from 1.47 +/- 0.74 to 9.44
      +/- 1.85 mm Hg; P < .01) and inspiratory (from 0.98 +/- 0.69 to 6.83 +/- 1.55 mm
      Hg; P < .01) intraabdominal pressures. These changes were transient, and all
      pressures became normal after 1 week. The antireflux barrier functioned properly
      under these new conditions because both LESP and the diaphragmatic pinch-cock
      pressure (DPP) increased, from 20.3 +/- 3.63 to 26.5 +/- 4.31 mm Hg (P < .01) and
      from 16.4 +/- 7.25 to 22.5 +/- 4.36 mm Hg (P < .01), respectively, while LESL
      remained unchanged. CONCLUSION: Tight abdominal wall plication in the rat
      generates high intraabdominal pressures and thus reinforces the
      transdiaphragmatic pressure gradients, but these conditions elicit a healthy
      barrier response with sphincteric reinforcement. In addition, these changes are
      transient and fade out some time after operation. These facts should be taken
      into account for understanding the pathogenesis of GER after repair of abdominal
      wall defects in human babies.

PMID- 8986984
TI  - Anomalous pancreatico-biliary junction--report of a new experimental model and
      review of the literature.
AB  - A model of anomalous pancreatico-biliary junction was developed and used to
      investigate a possible role in the development of choledochal cyst and tumors of
      the biliary tract. An anastomosis was constructed between an isolated pancreas
      duodenal segment and the gallbladder in 20 minipigs, but the results did not show
      any subsequent dilatation of the biliary tract, although intestinal metaplasia
      was observed in 20% of the animals. The severity of the epithelial changes was
      proportional to the duration of the experiment and may represent a premalignant
      change. A critical review of all reported animal models of anomalous
      pancreaticobiliary junction also is provided.

PMID- 8986985
TI  - Effect of BN 50727 on pathological findings and tissue platelet activating factor
      levels during ileal ischemia in newborn piglets.
AB  - The role of platelet activating factor (PAF), a potent ulcerogen mediator in the
      digestive tract, is thought to be important in the genesis of necrotizing
      enterocolitis. The aim of this study was to evaluate the role of PAF in the
      perpetuation and aggravation of gastrointestinal damage resulting from limited
      ischemia in the 2-day-old piglet using a natural PAF antagonist (BN 50727).
      Animals were separated into six groups: U4, controls; S, sham operated animals
      undergoing laparotomy; I4 and I9, ligation of the mesenteric vessels in the last
      ileal loop; IT4 and IT9, same procedure together with treatment with BN 50727 (50
      mg/kg) orally before and after surgery and intraperitoneally during surgery.
      Animals were killed at day 4 in groups U4, S, I4 and IT4 and at day 9 in groups
      I9 and IT9, with histological studies and mediator measurements taken.
      Macroscopic and histological lesions of intestinal wall in groups I4, I9, IT4 and
      IT9 were similar to those of human neonatal necrotizing enterocolitis and did not
      vary according to the absence or the presence of BN 50727 treatment (P = .7, I4 v
      IT4 and P = .9, I9 v IT9). Peritoneal bands were significantly reduced in treated
      groups IT4 and IT9 as compared with untreated ones I4 and I9 (P = .003). Mucosal
      PAF levels in the terminal ileum were higher in group I4 than in groups U4 or I9.
      In the upper loop, mucosal PAF levels were comparable in all groups. An increase
      in stool PAF levels was observed only in group I9 (26.4 ng/g v 4.7 ng/g, I9 v U4
      + S, P < .05), whereas values comparable to those observed in controls were
      detected in other groups (I4, 7.2 ng/g; IT4, 4.5 ng/g; IT9, 6.8 ng/g). Tumor
      necrosis factor alpha (TNF alpha) measurements did not exhibit any difference
      between groups. Using a PAF antagonist, the role of PAF in the aggravation of
      intestinal damage after ischemia was not remarkable because treatment did not
      induce any modifications of parietal intestinal lesions. PAF antagonists appeared
      to reduce significantly the local peritoneal consequences of local inflammation.

PMID- 8986986
TI  - Evaluation of the lower urinary tract function in caudal duplication (dipygus)
      anomaly.
AB  - Caudal duplication is a rare anomaly with less than 30 reported cases. For those
      patients who also have double bladders, there are not enough data regarding the
      function of the lower urinary tract. A boy with caudal duplication anomaly was
      evaluated fluoroscopically and urodynamically. The results of the evaluation
      showed that the bladders were filling and emptying synchronously with normal and
      almost identical detrusor pressures. The child did not require either or both
      bladders to be resected. Because the level of the duplication in dipygus cases
      varies, thorough evaluation of the lower urinary tract, including urodynamics,
      should be considered for every case.

PMID- 8986987
TI  - Anorectal malformation: a new anatomic variant resembling an H-type fistula.
AB  - A new anatomic variant of an anorectal malformation resembling an H-type fistula
      was observed in a newborn girl. This variant consisted of a high-grade stenosis
      of the anal canal below the level of the levator muscle with a blind-ending
      fistulous tract originating from the stenotic segment and running toward the
      posterior wall of the vestibulum. The embryogenesis of this malformation remains
      to be seen.

PMID- 8986988
TI  - New application of endoloop for rectal polypectomy.
AB  - The primary difficulty in performing rectal procedures such as polypectomy in
      children is the limited space in which to suture after a biopsy. Use of an
      available laparoscopic pretied loop ligature has been adapted to simplify these
      cases.

PMID- 8986989
TI  - Stomach rupture associated with physical struggle in a child.
AB  - A 5-year-old girl with spontaneous rupture of the stomach was treated
      successfully with excision of the ischemic edges of the perforation with primary
      repair. In this case, vigorous resistance against medical measurement resulted in
      rupture of the stomach, which was already distended with a large amount of fluid
      and air. The child survived following immediate surgical intervention and
      intensive postoperative care.

PMID- 8986991
TI  - Carpet bezoar obstruction of the small intestine.
AB  - Bezoars are food or fiber concretions of the alimentary tract, which infrequently
      cause intestinal obstruction. The authors describe a case of a 7-year-old child
      with pica in whom a synthetic fiber bezoar obstruction of the small intestine
      developed at the site of a previously stapled intestinal anastomosis.

PMID- 8986990
TI  - Severe hypertension and cardiac failure associated with neuroblastoma: a case
      report.
AB  - The authors report on 3-year-old-girl with neuroblastoma complicated by severe
      hypertension and cardiac failure. She had cardiomegaly and pleural and
      pericardial effusions. Echocardiogram showed left ventricular hypertrophy and
      decrease of the left ventricular ejection fraction to 0.36 (normal > .40).
      Abdominal computed tomographic scan indicated a 7 x 7-cm tumor in the left
      suprarenal area. There was a marked increase in catecholamines and metabolites in
      her body fluids. After hypertension was controlled with doxazosin (a long-acting
      alpha 1 adrenergic blocker), her cardiac function gradually improved. A tumor was
      surgically removed and diagnosed as a poorly differentiated ganglioneuroblastoma.
      Preoperative differentiation between neuroblastoma and pheochromocytoma was not
      possible on the basis of catecholamine analysis or imaging studies including
      computed tomography scan and magnetic resonance imaging. It is important to
      control hypertension quickly in the patients with catecholamine-induced
      cardiomyopathy to facilitate surgical intervention for diagnosis and treatment.

PMID- 8986992
TI  - Mischievous magnets: unexpected health hazard in children.
AB  - The authors encountered two cases of gastrointestinal complication caused by
      ingested magnetic beads. Because of the magnetic property, the steel beads,
      components of bracelets or necklaces worn for naturalistic healing power, have
      caused perforations, fistula formation, and obstruction. The authors believe the
      public should be warned of the health hazard of such devices.

PMID- 8986994
TI  - Dicephalus dipus dibrachius: an unusual case of conjoined twins.
AB  - Conjoined twinning is a rare anomaly, occurring in one of every 50,000 births.
      Dicephalus dipus dibrachius is an extremely rare form of conjoined twinning in
      which the infant has two arms, two legs, one trunk, but two heads. These infants
      are often stillborn or die shortly after birth. The authors describe a case of
      dicephalus twinning with 11-day survival. A thorough investigation using multiple
      imaging modalities (plain radiographs, contrast studies, ultrasonography, and
      magnetic resonance imaging) demonstrated that these twins had separate spinal
      columns but shared multiple internal organs including heart, liver, pancreas,
      intestine and bladder. Based on the anatomy of this case, the authors conclude
      that separation of dicephalus dipus dibrachius twins should not be attempted.

PMID- 8986993
TI  - Child abuse as a cause of traumatic chylothorax.
AB  - Chylothorax is an uncommon condition that may be associated with significant
      morbidity and mortality. The authors report a case of traumatic chylothorax
      attributed to child abuse and describe our management with tube thoracostomy and
      nutritional support with medium-chain triglycerides. Child abuse should be
      suspected in any case of chylothorax when no other etiology is evident and
      particularly when other signs of abuse are present.

PMID- 8986995
TI  - Pneumatic intussusception reduction via a colostomy: case report.
AB  - Intussusception is uncommon in infants with a colostomy. The authors present the
      first documented case of intussusception in an infant with a colostomy in which
      pneumatic reduction was achieved via the stomal opening. The inflated balloon of
      a Foley catheter was plugged against the stoma at skin level and a tight seal was
      obtained. Successful reduction was achieved without any adverse effects to the
      patient.

PMID- 8986996
TI  - Synovial sarcoma of the esophagus.
AB  - A 14-year-old girl presented with dysphagia and weight loss. Barium swallow,
      computed tomography, and endoscopy showed a polypoid intraluminal mass in the
      cervical esophagus. The tumor was locally resected and postoperative chemotherapy
      and radiotherapy were administered. Histological examination of the surgical
      specimen established a diagnosis of synovial sarcoma. The patient remains free of
      discernible disease 30 months after surgery. Esophageal sarcomas are rare tumors.
      This appears to be the second reported case of esophageal synovial sarcoma in a
      child.

PMID- 8986997
TI  - Megacystis microcolon intestinal hypoperistalsis syndrome: evidence of a primary
      myocellular defect of contractile fiber synthesis.
AB  - Two infant boys with megacystis microcolon intestinal hypoperistalsis syndrome
      (MMIHS) are reported. Presenting with neonatal intestinal obstruction, they
      underwent laparotomies that showed megacystis, microcolon, and aperistaltic
      shortened small bowel without any mechanical obstruction. Patient 1 gradually
      improved and is developing normally at home, on a normal diet without
      genitourinary or gastrointestinal complaints (now 11 years old). Patient 2, who
      underwent vesicoamniotic drainage antenatally, never developed adequate
      gastrointestinal or genitourinary function in spite of appropriate diversion and
      pharmacologic support. He showed progressive deterioration and died at the age of
      7 months. Detailed histo-immuno- and ultrastructural pathology assessment,
      although confirming results in the existing literature in some aspects, showed
      previously unreported neuronal dysplastic changes associated with increased
      laminin and fibronectin. Although patient 1 showed ultrastructural features of
      vacuolar degeneration of smooth muscle as reported in the literature, patient 2
      showed ultrastructural and histochemical evidence of excessive smooth muscle cell
      glycogen storage with severely reduced contractile fibres displaced to the
      extreme periphery of the cells, suggesting a fundamental defect of glycogen
      energy utilization. A deficiency of fiber synthesis as the alternative primary
      defect is discussed. In both cases, a two-step genetic defect may explain the
      variability in clinical outcome and pathological findings.

PMID- 8986998
TI  - Successful endoscopic balloon dilatation for hypertrophic pyloric stenosis.
AB  - The authors successfully applied endoscopic balloon dilatation for the treatment
      of hypertrophic pyloric stenosis (HPS). The patient was an infant girl who had
      undergone repair of a giant omphalocele. Endoscopic balloon dilatation was
      performed using a 9-mm endoscope and an 8-mm polyethylene terephthalate (PET)
      balloon dilator. Dilatation was performed three times for 10 minutes. Vomiting
      continued after the dilatation. At the second session, dilatation was performed
      using a 12-mm PET balloon dilator. The 9-mm endoscope then passed through the
      pylorus. The patient has had no episodes of vomiting since the second treatment.
      This procedure is an important therapeutic option for selected patients with HPS.

PMID- 8987000
TI  - Management of giant omphalocele by progressive external compression: case report.
AB  - The management of giant omphalocele remains a major surgical challenge. A staged
      approach is mandatory to achieve an uncomplicated reduction. The case of a child
      conservatively and successfully treated by progressive external compression of
      the herniated organs and viscera using an elastic bandaging is described here.
      The complete integration of the omphalocele content and the closure of the
      abdominal wall were obtained in 9 days. No ventilatory support was required. The
      procedure is easy, safe, effective and inexpensive. Large base and intact
      amniotic sac are prerequisites for feasibility.

PMID- 8986999
TI  - Recurrent apparent life-threatening event relieved by glossopexy.
AB  - An infant with repaired esophageal atresia presented with several apparent life
      threatening events (ALTEs). He had upper airway instability, gastroesophageal
      reflux (GER), and tracheomalacia. Oxygen breathing test results showed a modest
      increase in arterial Po2 consistent with the development of an intrapulmonary
      shunt from absorption collapse of some hypoventilated areas of the lung.
      Glossopexy was followed by improvement in upper airway stability, normal oxygen
      test, and disappearance of ALTE. These findings support the concept that upper
      airway instability, obstructive apnea, lower airway instability, absorption
      collapse, massive intrapulmonary shunt, and ALTE are the result of a cascade
      reaction. The authors conclude that infants with ALTE associated with obstructive
      apnea and O2 shunting require glossopexy to reduce the risk of sudden death.

PMID- 8987001
TI  - Acquired biliary atresia.
AB  - Three infants are described in whom acquired biliary atresia developed during the
      perinatal period. In two cases this was related to a spontaneous perforation of
      the bile duct, and in the other it probably was related to previous surgery for
      duodenal and ileal atresias. Clinically, the symptoms in these patients differed
      from the congenital forms of biliary atresia; two of the infants had dilated
      intrahepatic ducts on ultrasonography, and all had restriction of disease to the
      extrahepatic bile ducts and an excellent response to surgery.

PMID- 8987002
TI  - Video-assisted thoracoscopic pneumonectomy for bronchial carcinoid tumor in a 14
      year-old girl.
AB  - A 14-year-old girl with a carcinoid tumor of the proximal right bronchus
      intermedius underwent a video-assisted thoracoscopic pneumonectomy. She was fully
      ambulant within 48 hours of surgery, had less pain than that normally associated
      with standard thoracotomy, and was discharged on the 7th postoperative day.

PMID- 8987003
TI  - Endourologic removal of upper airway foreign objects: case report.
AB  - The authors report on removal of upper airway foreign bodies using endourology
      baskets and stone graspers in a patient who did not respond to standard upper
      airway management. The procedure was safe and effective with localization and
      successful removal of most of the stone burden.

PMID- 8987004
TI  - Angiosarcoma of the liver in children.
AB  - The clinico-pathological features of four cases of pediatric hepatic
      angiosarcomas are described. One case was initially diagnosed in infancy and
      underwent resection of a left-sided benign hemangioendothelioma of the liver.
      Further resection of a lesion in the right liver was followed by malignant
      transformation. Primary hepatic resection of the tumor was not possible in three
      other cases, and all received courses of chemotherapy without significant tumor
      shrinkage. One child underwent liver transplantation but died 4 months later of
      immunosuppression complications. The remaining three children died of
      disseminated malignancy. Histological verification of malignancy was difficult in
      three cases in which there was discrepancy between the rapid growth of the liver
      tumor and the microscopic features of benign hemangioendothelioma.

PMID- 8987005
TI  - Immune deficiency in familial duodenal atresia.
AB  - The familial occurrence of duodenal atresia is uncommon. This study evaluated the
      inheritance patterns, the nature and associations, and the presence of
      immunologic deficits in duodenal atresia recurring in at least three siblings
      each in two nonrelated families. In the first family, an association with
      Fanconi's anemia was observed in three of seven pregnancies (2 boys, 1 girl)
      suggesting an autosomal recessive mode of transmission. Patients died as a result
      of overwhelming (fungal) septicemia in association with pancytopenia. In a second
      family, identical multiple atresias occurred in two female siblings born 18
      months apart and a third child with a duodenal stenosis. Overwhelming sepsis and
      a T-cell dysfunction was seen in the postoperative period, which had partially
      corrected by follow-up at 5 months. A history of family occurrence of duodenal
      atresia should alert the physician to the possibility of associated pathology
      including immune deficiency states.

PMID- 8987006
TI  - Percutaneous Cecostomy: a new technique in the management of fecal incontinence.

PMID- 8987008
TI  - Neutrality and psychoanalysis: separation, divorce, or a new set of vows?

PMID- 8987009
TI  - Free association and analytic neutrality: the basic structure of the
      psychoanalytic situation.
AB  - This paper re-examines within a contemporary context an essential foundation of
      classical technique, the psychoanalytic situation. Defined in terms of basic
      elements of psychoanalytic relatedness which make possible the most profound
      exploration of human motivation, its core structure is viewed as an extraordinary
      interpersonal arrangement anchored by two clearly differentiated yet
      complimentary ways of relating: free-association and analytic neutrality. The
      patient's role, organized by the prerequisites of expressive freedom, is counter
      posed with the psychoanalyst's, which is structured to empower listening and
      understanding. Elaborating the parameters of this unique relationship, the
      authors emphasize the synergic effects of each participants' activity in creating
      a vehicle for destabilizing neurotic equilibrium. An extensive discussion of
      analytic neutrality, conceived as guiding ideal that informs all the analyst's
      attitudes and actions in the exploration of psychic reality, is presented.
      Specifically, the authors distinguish three essential dimensions which bear upon
      the interactive process: neutrality with regard to conflict, neutrality with
      regard to sequence, and neutrality with regard to transference. In contrast to
      the rigid constraint on human responsiveness often caricatured in the literature,
      this vision of technical neutrality establishes its vital contribution to the
      integrity, depth, and tone of any analytic process that unfolds.

PMID- 8987010
TI  - The therapeutic action of psychoanalysis: abstinence and informative experiences.
AB  - In recent years a number of analytic concepts have been subject to scrutiny, with
      the value of interpretations, the usefulness of abstinence, the possibility of
      neutrality, all questioned. One reason for the skepticism about interpretations,
      in particular, is that before a patient can use an interpretation for psychic
      change, his perceptual frame must change, a process that is rarely initiated by
      the verbal content of an interpretation alone. Instead, alterations in perception
      usually require experiences which are discordant with expectations. In this paper
      the author demonstrates how the nonverbal elements of an intervention, the action
      communications, provide informative experiences, creating the dissonance between
      expectation and eventuality which makes psychic change possible. Case vignettes
      are presented to illustrate this point as well as to support the idea that when
      nonverbal experiences contribute to lasting change within a patient, the
      therapeutic benefit does not accrue primarily from the gratification provided by
      the experience, but from how the experience informs the patient about his mode of
      thinking, perceiving, and reacting.

PMID- 8987011
TI  - The ego and its significance in analytic interventions.
AB  - Freud's view of the ego as Januslike, the one component of the psychic system
      turned toward the external world yet partly unconscious, should have insured its
      centrality in clinical interventions. However, history and experience do not bear
      this out. It is argued that a core part of the change process in analysis lies in
      the modifications that occur in ego functioning, making it necessary to carefully
      consider the role of the ego in clinical technique. Numerous clinical examples
      are presented to show the manner and significance of such an approach.

PMID- 8987012
TI  - Emerging indicators of ego growth and associated resistances.
AB  - In this paper the technique of resistance analysis is extended beyond a focus on
      defenses against aggressive drive derivatives to include a focus on resistances
      based on libidinal conflicts and resistances which stem from defenses against
      accessing and using autonomous ego functions. For example, patients may resist
      progress by forming primary defenses against expression of joyful affects,
      increased capacity to think, and/or new possibilities for effective action. This
      expanded focus for analysis of resistance permits us to build a technique bridge
      between drive-defense perspectives and ego psychology, it highlights the need to
      analyze the sense of danger involved in autonomous ego functioning, and it points
      to a way of freeing such functioning from the influences of resistance.

PMID- 8987013
TI  - The perverse subject of analysis.
AB  - In this paper I suggest that the analysis of perversion necessarily involves the
      elaboration and analysis of a perverse transference-countertransference. Both
      analyst and analysand contribute to and participate in the perverse transference
      countertransference which intersubjective construction is powerfully shaped by
      the perverse structure of the patient's unconscious internal object world. In the
      fragment of an analysis that is presented, I illustrate the way in which the
      analyst makes use of his experience in (of) the transference-countertransference
      in gaining understanding of the perverse scenario that the patient is utilizing
      as a form of psychic organization, defense, communication, and object
      relatedness. I discuss the analyst's use of his own unobtrusive, mundane
      thoughts, feelings, fantasies, ruminations, sensations, and so on, in the service
      of understanding the perverse transference-countertransference, which
      understanding is utilized in the formulation of transference interpretations. The
      perversity of the transference-countertransference is viewed as deriving from the
      patient's defensive use of particular forms of sexualization as a way of
      protecting himself or herself against the experience of psychological deadness.
      Compulsive erotization is understood as representing a method of creating an
      illusory sense of vitality. The subversion of the recognition of the experience
      of psychological deadness is achieved in part through compulsively enlisting
      others in the enactment of exciting, erotized, and often dangerous substitutes
      for the experience of being alive.

PMID- 8987014
TI  - Seduction trauma: representation, deferred action, and pathogenic development.
AB  - Seduction trauma refers to a range of phenomena currently described under the
      rubric of child abuse. Freud elucidated the fantasy distortion and elaboration of
      traumatic experience and retained the importance of actual trauma. Psychic trauma
      is associated with the alteration of self and object representations and ensuing
      new identifications, e.g., with victim and aggressor. The "deferred action" of
      psychic trauma is an antiquated concept and psychic trauma has immediate effects
      as well as far reaching developmental consequences. Prior trauma predisposes to
      later traumatic vulnerability and to trauma linked to phase specific unconscious
      conflict. The pathogenesis of child sex abuse and the enactment of oedipal incest
      extends before and after the oedipal phase, is often associated with other forms
      of abuse, and has a history of pathogenic parent-child relationship.

PMID- 8987015
TI  - Memory systems and the psychoanalytic retrieval of memories of trauma.
AB  - Increasingly, psychoanalysis has confronted the issue of recovered memories of
      childhood trauma. Based on trauma research, the concept of a special traumatic
      memory has evolved. Overwhelming psychic experience is thought to generate a
      defensively altered state of consciousness (specifically dissociation), which
      encodes memory in unassimilated visual, somatic, and behavioral, rather than
      linguistic modes. Analytic reevocation and interpretation of the original altered
      states of consciousness then permits the transformation of "early" traumatic
      memory into "later" explicit memory. Examined from the vantage point of
      contemporary cognitive research and theory, underlying flaws may be found in
      these propositions when they are extended to patients without explicit memory of
      trauma: first, dissociation is a chameleonlike process, perhaps as closely
      associated with suggestibility as with trauma; second, state-dependent learning
      does not adequately account for the absence of explicit memory; and third,
      implicit memory does not map onto explicit memory in any direct or simple
      fashion. Consequently, the clinical application of current propositions about
      traumatic memory to patients without explicit memory of trauma may warrant
      considerable caution. Provisional guidelines are offered for estimating the
      validity of retrieved memories of trauma.

PMID- 8987016
TI  - Suggestion and veridicality in the reconstruction of sexual trauma, or can a bait
      of suggestion catch a carp of falsehood?
AB  - Freud used the term suggestion in psychoanalysis in different ways, including
      suggestion as an integral part of the transference and suggestion in the sense of
      undue influence or technical error. This distinction can be expressed in terms of
      the patient's suggestibility (capacity for transference) and the analyst's
      unwarranted suggestion or persuasion representing countertransference,
      theoretical bias, or a departure from technical neutrality. Whether suggestion is
      explicit or implicit, the effects of suggestion and suggestibility may be mutual
      and reciprocal. To the extent that a psychoanalyst maintains the goal of
      technical neutrality, undue suggestion is likely to be minimal. To the extent
      that it occurs for transferential or countertransferential reasons, suggestion
      may itself be analyzed. Problems of suggestion are more likely to occur and
      persist when they are part of the analyst's theoretical orientation, influencing
      the course of the analysis and expressing compromise formations for both patient
      and analyst. At times, even tentatively stated words or unintended behaviors of
      the analyst can have a dynamic impact that may not be readily analyzed. The
      analytic situation itself may have retrospective (nachtraglich) action. A
      previously published case is described in which an apparent enactment led the
      analyst to urge a reconstruction of sexual abuse even though the patient never
      actually recalled what was presumed to have been fellatio. The need for technical
      neutrality and alternative reconstructions in such cases is considered. The
      degree to which the personality and goals of the analyst influence the course of
      reconstruction remains a vexing issue for psychoanalysis as a scientific
      endeavor. There is a need for detailed analytic case studies in which alternative
      reconstructions can be compared by investigating opportunities for external
      confirmation or falsification.

PMID- 8987017
TI  - Welfare reform.

PMID- 8987018
TI  - Parents' resources and home management of the care of chronically ill infants.
AB  - PURPOSE: To identify resources of parents or primary caretakers who managed
      chronically ill infants at home and to determine psychometric properties of Home
      Care Resources Inventory (HCRI). DESIGN: Cross-sectional, descriptive SETTING:
      Outpatient clinics. PARTICIPANTS: Parents or primary caretakers (N = 100) of
      chronically ill infants who were discharged from hospital at least one week; 93%
      of sample were mothers; infants' ages ranged from 1-22 months. MAIN OUTCOME
      MEASURES: HCRI, the Spielberger State Anxiety Inventory, and a demographic
      questionnaire. RESULTS: Parents reported strong resources in the area of support
      and inconsistent resources in areas of coping, time, and respite. The HCRI has
      acceptable psychometric properties. CONCLUSIONS: Identifying resources,
      especially personal time and respite, is essential for successful home management
      of chronically ill infants. The HCRI can be used to pinpoint areas that are
      strong or weak in the two resource areas measured.

PMID- 8987019
TI  - Shots for tots: Louisiana's infant immunization initiative.
AB  - PURPOSE: To describe the "Shots for Tots" immunization initiative, a community
      based approach to overcoming barriers to timely immunizations. POPULATION:
      Children in southwest Louisiana, ages 1 month to 5 years, requiring
      immunizations. CONCLUSIONS: The "Shots for Tots" immunization initiative has been
      successful in improving immunization rates. PRACTICE IMPLICATIONS: With the
      increase in community-based practice and the resurgence of many vaccine
      preventable diseases, this program can serve as an example to pediatric nurses
      involved in prevention and primary care in their efforts to improve immunization
      rates.

PMID- 8987021
TI  - Children, coping, and the stress of illness: a synthesis of the research.
AB  - PURPOSE: To synthesize and critique the current research on coping strategies
      used by children who are ill, to identify gaps in the research base, and to
      provide direction for practice, future research, and theory development.
      POPULATION: 32 research articles on coping strategies used by children with
      chronic or acute illness. CONCLUSIONS: Children's repertoire of coping strategies
      is the same during health and illness, although the frequency or effectiveness of
      some of the strategies is often different. PRACTICE IMPLICATIONS: Much more in
      depth descriptive and longitudinal research is needed, particularly how, when,
      and why coping strategies are learned, retained, and later discarded. Research is
      needed to examine the relationship between coping and health outcomes, and on the
      effectiveness of nursing interventions designed to influence children's coping
      behavior.

PMID- 8987020
TI  - Smoking status among women in households with young children.
AB  - PURPOSE: To identify sociodemographic and health related correlates of smoking
      status among women in households with young children. DESIGN: A secondary
      analysis of the 1992 California Behavioral Risk Factor Surveillance System public
      use data tape. PARTICIPANTS: Women (N = 520) in households with very young
      children (< or = 5 years of age). MAIN OUTCOME MEASURES: Current smoking status.
      RESULTS: Approximately 18% were current smokers; more than 40% smoked more than
      10 cigarettes each day. A majority of smokers indicated a high level of nicotine
      addiction, but had plans to quit. Smoking prevalence varied by sociodemographic
      variables with higher rates for unmarried, less than college educated, and
      unemployed participants. Health status also was related to smoking, with higher
      rates among those with poor health and those limited in activities. CONCLUSIONS:
      Smoking is one way of coping with the stressors of daily life, including those
      associated with caring for young children. Special cessation efforts may be
      needed for the unemployed, the unmarried woman, and for those in poor health.

PMID- 8987022
TI  - Failure to thrive.

PMID- 8987023
TI  - Use of visual organizers in place of nursing care plans when caring for children.

PMID- 8987024
TI  - Colcemid alters S phase and other parameters in skin during chronic exposure to
      benzo(a)pyrene.
AB  - The administration of Colcemid for collecting mitotic figures in a carcinogenesis
      study, using benzo(a)pyrene (BaP), diminished the experimental differences
      between exposed and control mice. A dose-related increase in noncollected mitotic
      index (n-mitotic index) was seen in keratinocytes in the dorsal epidermis of mice
      which received four weekly treatments of BaP at 16, 32 and 64 micrograms in 50
      microliters of acetone. In contrast, the number of mitotic figures collected for
      4 hr by Colcemid block (c-mitotic index) was depressed at 16 micrograms,
      unchanged at 32 micrograms, and elevated at 64 micrograms of BaP. Weekly
      treatments with 4,8 or 16 micrograms BaP for 3-8 months induced an elevation in
      both n-mitotic and c-mitotic indices. The differences in results produced by the
      two methods of determining mitotic index depended upon dose and duration of
      treatment with BaP. The administration of Colcemid to acetone-treated mice
      increased the labeling index (number of labeled cells) and reduced the rate of
      DNA synthesis (low grain count per keratinocyte nucleus). After chronic
      application of BaP, Colcemid abrogated the increase in labeling index, but
      produced no additional effect on the number of grains per labeled keratinocyte.
      The modifying effect of Colcemid was greatest when administered during the peak
      of the tissue response to BaP. A number of significant changes in morphology of
      the skin associated with chronic exposure to BaP were attenuated by the use of
      Colcemid.

PMID- 8987025
TI  - Selective adsorption: a new method for purification of protein A-gold complexes.
AB  - Protein gold complexes are prepared by adding gold colloids to cytochemically
      active proteins in solution. The gold particles of the colloid form complexes
      with the protein spontaneously, but some of the protein remains uncomplexed.
      Currently, when protein A-gold complexes are prepared, the uncomplexed protein. A
      is separated from the complex by ultracentrifugation, which is a lengthy
      procedure and requires special equipment. This report describes a simple and
      rapid method for removing uncomplexed protein A from freshly-prepared "crude"
      protein A-gold at the laboratory bench. In this method, larger gold particles of
      15-nm diameter are added to a crude protein A-gold preparation made with smaller
      particles (e.g.,6nm diameter). The 15-nm particles adsorb uncomplexed protein A
      preferentially, but do not form complexes with already-formed 6-nm protein A
      gold. The adsorbed protein A, attached to the 15-nm particles, can then be
      sedimented in a bench centrifuge, leaving the purified 6-nm protein A-gold
      complexes in the supernatant. The stability, immunocytochemical activity, and
      degree of aggregation of the protein A-gold complexes prepared by this method are
      comparable to protein A-gold complexes prepared by ultracentrifugation. The
      method is simple to perform, avoids lengthy purification procedures, and yields
      complexes with reproducible labelling characteristics.

PMID- 8987026
TI  - Cross-sectional sample preparation by focused ion beam: a review of ion-sample
      interaction.
AB  - A focused ion beam (FIB) was applied for cross-sectional sample preparation with
      both transmission electron microscopes (TEM) and scanning electron microscopes
      (SEM). The FIB sample preparation has the advantage of high positioning accuracy
      for cross sections. On the other hand, a broad ion beam (BIB) has been
      conventionally used for thinning TEM samples. Although both FIB and BIB use
      energetic ion beams, they are essentially different from each other in many
      aspects such as beam size, beam current density, incident angle of the beam with
      respect to cross sections, and beam scanning (i.e., dynamic or static beam). In
      this study, FIB cross-sectioning is compared with BIB thinning. We review
      inherent characteristics such as positioning accuracy and uniformity of cross
      section, radiation damage, and beam heating. Discussion is held from a view-point
      of ion beam and sample interaction.

PMID- 8987027
TI  - Thin foil preparation of metal particles in brittle ceramic matrices.
AB  - Thin foil preparation for metal particles in brittle ceramic matrices is
      particularly difficult, due to differential thinning of the component materials.
      This paper considers the preparation of thin foils of stony meteorites. Stony
      meteorites have a composite nature consisting of small metal particles (< 200
      microns) embedded in an inherently brittle silicate matrix. Specimens of this
      type are difficult to prepare as thin foils because the area of interest is
      limited to specific regions within the metal particles. The problems of thin foil
      preparation of metal particles in the stony meteorites were overcome by
      developing a technique involving electrochemical polishing prior to ion beam
      thinning. The metal particles were first separated from the silicate matrix and
      then embedded in Epo-Tek H20E silver epoxy. This specific epoxy was selected for
      its good electron conductivity which allowed the specimen to be thinned by the
      electrochemical polishing technique. Specimens prepared by this technique have
      permitted the direct observation and characterization of the metallic phases in
      stony meteorites.

PMID- 8987028
TI  - Participation of endodermal epithelial cells on the synthesis of plasma LDL and
      HDL in the chick yolk sac.
AB  - We ultrastructually examined the chick yolk sac endodermal epithelium and
      evaluated our findings in combination with the biochemical analysis of serum and
      yolk lipoproteins. Twenty-five to 30 nm-sized particles were demonstrated to be a
      principal element of the extracellular yolk mass and these were determined to be
      yolk very low density lipoprotein (VLDL). The particles were shown to be taken up
      by the epithelial cells via coated pits and engulfed by plasma membrane
      invaginations together with yolk subdroplets, another element of the yolk mass.
      Through apical vacuoles, the two yolk elements were incorporated into yolk drops,
      which were identified to be one of the lysosomal structures by a cytochemical
      procedure using acid phosphatase (AcP)ase activity. During the last week of
      incubation, which is the final third of the incubation period, the digestion
      seemed to progress rapidly in the yolk drops, which came to resemble
      lipolysosomes; lipoprotein production became active as expressed by an enlarged
      Golgi apparatus. The newly produced lipoprotein particles were electron-lucent
      and irregular in size (50-120 nm). They were sequestered in secretory vacuoles
      and secreted from the vascular surface of the epithelial cells. Finally, the
      particles were thought to be taken into the vitelline circulation as plasma
      lipoproteins. The major component of lipoprotein in serum was determined to be
      low density lipoprotein (LDL) and high density lipoprotein (HDL), while
      cholesterol content was found to increase during incubation. We concluded that
      endodermal epithelial cells participate the synthesis of plasma LDL and HDL. For
      this synthesis the cells probably apply lipids and apo-protein generated from
      yolk VLDL degradation.

PMID- 8987030
TI  - Processing Trichomonas vaginalis for scanning electron microscopy.

PMID- 8987029
TI  - Immunohistochemical study and western blotting analysis of titin-like proteins in
      the striated muscle of Drosophila melanogaster and in the striated and smooth
      muscle of the oligochaete Eisenia foetida.
AB  - The presence and distribution of titin-like proteins have been examined in
      transversely striated muscle of Drosophila melanogaster, in obliquely striated
      muscles (body wall and inner muscular layer of the pseudoheart) and smooth muscle
      (outer muscular layer of the pseudoheart) from the earthworm Eisenia foetida by
      means of Western blotting analysis, light microscopy immunohistochemistry, and
      electron microscopy immunogold labeling, using antibodies anti vertebrate
      (chicken) titin (3,000 kDa) and arthropod (D. melanogaster) mini-titin (twitchin
      or projectin) (700 kDa). To determine whether these antibodies immunoreact non
      specifically against vertebrate titin, mouse skeletal muscle was also studied. As
      negative control, mouse smooth muscle was used. Immunoreaction to mini-titin was
      found in all the invertebrate muscles studied. For each of these muscles, Western
      blotting analysis of mini-titin showed a single band, at approximately 700 kDa.
      Electron microscopy immunolabeling to this protein was observed along the whole
      sarcomere length (A bands and I bands) in both transversely striated muscles of
      the insect and obliquely striated muscles of the earthworm, although the number
      of immunogold particles was more abundant in the insect muscles. Mini-titin
      immunolabeling was also observed in the smooth muscle cells that formed the outer
      layer of the earthworm pseudoheart although in lower amounts than in the
      obliquely striated muscle. The absence of true sarcomeres in the smooth muscle
      cells did not permit to determine the extension of mini-titin immunolabeling. No
      immunoreaction to this protein was found in the striated and smooth muscles of
      the mouse. Immunoreaction to titin was only observed in the mouse skeletal
      muscle, in which both A bands and I bands appeared immunolabeled. Present results
      show that mini-titin in the invertebrate muscles studied differs
      immunohistochemically from vertebrate titin and, in contrast with titin, mini
      titin is also present in invertebrate smooth muscles.

PMID- 8987031
TI  - Deblurring and 3D-like rendering of light microscope images.

PMID- 8987032
TI  - Improved fixation and contrast of insect Malpighian tubules using osmium
      tetroxide-potassium ferricyanide.

PMID- 8987033
TI  - XTEM sample preparation technique for n-type compound semiconductors using
      photochemical etching.
AB  - A sample preparation technique based on photochemical etching (PCE) is described
      for cross-sectional transmission electron microscopy (XTEM) of n-type compound
      semiconductors. XTEM samples of an InGaAsP/InP single-layer structure, prepared
      by using a moderately focused laser beam and Br2-methanol solution, gave high
      quality, damage-free XTEM images. The PCE technique is applicable to other n-type
      compound semiconductors.

PMID- 8987034
TI  - Resistance to rocuronium in an epileptic patient on long-term carbamazepine
      therapy--a case report.

PMID- 8987035
TI  - Hazards of nitrous oxide administration in presence of venous air embolism.
AB  - Nitrous oxide administration in presence of venous air embolism results in its
      volume augmentation. The present case report of a 50-year old patient undergoing
      posterior fossa tumor excision in the sitting position demonstrates the hazards
      of nitrous oxide in presence of venous air embolism. Administration of 66%
      nitrous oxide 140 minutes after the incidence of air embolism resulted in a
      significant decrease of end-tidal carbon dioxide tension, moderate hypotension,
      and tachycardia, suggesting volume augmentation of the air embolism. The results
      of our case report are in contrast to that by Shapiro et al who noted that
      nitrogen washout following administration of 100% oxygen was complete 65 minutes
      after the occurrence of venous air embolism. Shapiro and colleagues suggest the
      use of nitrous oxide challenge as a diagnostic aid in deciding when lung
      excretion of intravascular air is complete. However, our case report implies that
      nitrogen washout was not complete 140 minutes after venous air embolism
      incidence. Accordingly, we recommend to stop nitrous oxide administration once
      air embolism is suspected and to refrain from its re-administration throughout
      the rest of surgery.

PMID- 8987036
TI  - Anesthesia for bronchoalveolar lavage--the use of modified CPAP system.

PMID- 8987037
TI  - Underwater seal for CPAP oxygenation during one-lung ventilation by a Univent
      tube.

PMID- 8987038
TI  - Trauma cases admitted to the surgical intensive care unit--progress and outcome.
AB  - A review of the trauma admissions to the Surgical Intensive Care Unit (SICU) at
      King Khalid University Hospital, Riyadh during the period from 30 October 1984 to
      29 October 1989 was made. A total of 181 cases constituting 15.7% of the total
      surgical admissions to the unit during that period were recognised. The main
      cause of the trauma was road traffic accidents (83.4%). The male to female ratio
      in this group was 6.3:1. Thirty patients died in the SICU, 16 died within 24
      hours of admission to the unit and the remaining 14 developed multiple organ
      failure prior to death. Positive cultures from different sites were obtained from
      50% of them. Recommendations are made to improve the management of similar cases.

PMID- 8987039
TI  - Use of the laryngeal mask for closed circuit anesthesia.
AB  - We examined whether the laryngeal mask could be used effectively in 70 patients
      breathings spontaneously during closed-circuit anesthesia. After administration
      of oxygen 101.min-1, anesthesia was induced and the laryngeal mask inserted.
      After 6 min of denitrogenation (3.51.min-1 nitrous oxide and 1.51.min-1 oxygen),
      the fresh-gas flow was decreased to the minimum required to maintain refilling of
      a ventilator bellows (Carden Ventmasta); nitrous oxide was turned off. A
      vaporiser outside the breathing system was set either by observing an end-tidal
      agent monitor or at 3-5 times greater than the required end-tidal concentration.
      The total fresh gas flow, hemodynamics and respiratory variables were monitored.
      Several types of operations were performed and lasted 9-126 min (mean 37 min).
      The average total fresh gas flow during the closed circuit period was 340 ml.min
      1 (range 200-500 ml.min-1). Blood pressure, heart rate and respiration were
      stable throughout anesthesia and there were no major side effects attributable to
      the technique. We believe that closed-circuit anesthesia in patients breathing
      spontaneously through the laryngeal mask, as described here, can be used safely,
      conveniently and effectively. This technique is suitable for surgical operations
      of short duration.

PMID- 8987040
TI  - Comparison of intubation conditions under propofol in children--alfentanil vs
      atracurium.
AB  - We have assessed tracheal intubating conditions in 45 ASA I-II children, aged 4
      14 years, undergoing elective ear, nose and throat surgery. After the induction
      dose of propofol 2.5 mgkg-1, Group I received alfentanil 10 ugkg-1, Group II
      received alfentanil 20 ugkg-1 and Group III received atracurium 0.5 mgkg-1 for
      tracheal intubation. The mean arterial pressure (MAP), heart rate (HR), arterial
      oxygen saturation (SaO2), end tidal carbondioxide (ETCO2) and intubation
      conditions were investigated. The quality of tracheal intubation was graded
      according to ease of laryngoscopy, position of the vocal cords, coughing and jaw
      relaxation. There were no significant differences in the overall assessment of
      intubating conditions between the three groups. Intubations were accomplished in
      94% of the patients in Group I and II, and 100% of the patients in Group III. We
      conclude that the combination of propofol and alfentanil conditions for treacheal
      intubation in children and attenuate the hemodynamic responses to layngoscopy and
      tracheal intubation.

PMID- 8987041
TI  - Reduction of propofol pain--fentanyl vs lidocaine.
AB  - To compare the local efficacy of lidocaine and fentanyl in reducing propofol
      injection pain (PIP), we conducted a prospective randomized double-blind study in
      75 ASA I and II adult patients. When administered 20 seconds before propofol with
      a venous tourniquet, lidocaine but not fentanyl or placebo, reduced the incidence
      of moderate to severe pain on subsequent injection of propofol (P < 0.001). Two
      patients (8%) in the lidocaine group (n = 25) experienced a moderate degree of
      pain and none experienced severe pain. Fifteen (60%) in the fentanyl group (n =
      25) experienced moderate or severe degrees of pain, compared with 15 (60%) in the
      saline group (n = 25). We conclude that lidocaine, acting locally, reduce
      propofol injection pain while fentanyl does not.

PMID- 8987042
TI  - Trafficking of lysosomal membrane proteins in polarized kidney cells.
AB  - Segregation of lysosomal membrane proteins into the endosomal system occurs via
      clathrin coated vesicles, either from the trans-Golgi network or the cell
      surface. In both cases, cytosolic signals present in these proteins interact with
      clathrin adaptor proteins. In polarized kidney MDCK cells, transport of lysosomal
      membrane proteins via the plasma membrane occurs in a polarized fashion through
      the basolateral domain. Here, we discuss recent developments on lysosomal
      membrane protein trafficking, with a particular focus on the transport of these
      proteins in polarized MDCK cells.

PMID- 8987043
TI  - Cellular mechanisms in renal tubular transport of divalent inorganic anions.
AB  - The kidney is a key organ in the homeostasis of inorganic phosphate (Pi) and
      sulfate (Si). These anions are freely filtered at the glomerular capillaries and
      are then reabsorbed in the proximal tubule. Studies on isolated membrane vesicles
      allowed the identification of Na/phosphate and Na/sulfate-cotransporters.
      Subsequently these transporters have been cloned. Vesicle studies documented that
      physiological (and pathophysiological) alterations involve regulated transport
      rates of these cotransporters. Molecular studies using cDNA-probes and specific
      antibodies indicated that physiological regulation occurs at multiple cellular
      levels (e.g. transcription/translation and membrane traffic).

PMID- 8987044
TI  - The ENaC channel as the primary determinant of two human diseases: Liddle
      syndrome and pseudohypoaldosteronism.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC) controls sodium
      reabsorption in the distal nephron. Its activity is under the control of
      aldosterone. The genes encoding ENaC have been identified and revealed an
      heteromultimeric structure of the protein composed of three homologous alpha beta
      gamma subunits. The role of ENaC in the pathogenesis of hypertension has been
      demonstrated by complete linkage of the gene encoding the beta and gamma subunits
      to an autosomal form of salt-sensitive hypertension. Analysis of these genes from
      patients affected by a sever hypertension (Liddle syndrome) identified mutations
      in the carboxy-terminus of ENaC subunits causing channel hyperactivity,
      consistent with increased sodium reabsorption in the distal nephron.
      Pseudohypoaldosteronism type-1 (PHA-1) represents a hereditary form of salt
      loosing nephropathy characterized by hyperkalemia, dehydration and metabolic
      acidosis. Analysis of genes encoding ENaC subunits in patients affected by PHA-1
      identified different types of mutations causing loss of function or a decrease in
      ENaC channel activity. These studies demonstrated the critical role of ENaC
      channel in the maintenance salt and extracellular fluid balance, and regulation
      of blood pressure.

PMID- 8987045
TI  - The aquaporin family of water channels in kidney.
AB  - The longstanding puzzle of membrane water-permeability was advanced by discovery
      of a new class of proteins known as the "aquaporins" (AQPs). First identified in
      red blood cells, AQP1 was shown to function as a water channel when expressed in
      Xenopus oocytes or when pure AQP1 protein was reconstituted into synthetic
      membranes. Analysis of the primary sequence revealed that the two halves of the
      AQP1 polypeptide are tandem repeats; site directed mutagenesis studies indicate
      that the repeats may fold into an obversely symmetric structure which resembles
      an hourglass. Electron crystallography elucidated the tetrameric organization of
      AQP1, and functional studies suggest that each tetramer contains multiple
      functionally independent aqueous pores. AQP1 is abundant in the apical and
      basolateral membranes of renal proximal tubules and descending thin limbs, and is
      also present in multiple extra renal tissues. AQP2 is expressed only in the
      principal cells of renal collecting duct where it is the predominant vasopressin
      (ADH, antidiuretic hormone) regulated water channel. AQP2 is localized in the
      apical membrane and in intracellular vesicles which are targeted to the apical
      plasma membranes when stimulated by ADH. Humans with mutations in genes encoding
      AQP1 and AQP2 exhibit contrasting clinical phenotypes. AQP3 resides in the
      basolateral membranes of renal collecting duct principal cells providing an exit
      pathway for water; AQP4 is abundant in brain where it may function as the
      hypothalamic osmoreceptor responsible for secretion of ADH. Continued analysis of
      the aquaporins is providing detailed molecular insight into the fundamental
      physiological problems of water balance and disorders of water balance.

PMID- 8987046
TI  - Diagnostic utility of somatosensory evoked potentials (SEPs) in presurgical
      assessment of cervical spondylotic myelopathy.
AB  - Median and tibial nerve SEPs were recorded in 27 patients with spondylotic
      myelopathy. SEP data were compared with clinical and MRI data. SEPs were abnormal
      in all but five patients. Segmental dysfuction of the cervical cord was observed
      in 12 patients (45%), whereas abnormality of dorsal column conduction was
      observed in 10 (37%) and 16 (59.3%) patients after median and tibial nerve
      stimulation, respectively. No clear correlation was found between the severity of
      MRI abnormalities and that of clinical presentation or SEP abnormalities.
      However, there was no patient with normal SEPs and severe MRI abnormalities,
      including narrowing of cervical cord diameter or impingement of the cervical cord
      or intramedullary T2 signal hyper intensity. Conversely, 8 of the 13 patients
      with no evidence of cord narrowing or T2 signal abnormality showed abnormal SEPs.
      This divergence between SEP and MRI data suggests that SEP recording should be
      included in presurgical assessment of these patients, especially those without
      clear MRI evidence of cervical cord compression.

PMID- 8987047
TI  - Scalp topographic mapping of middle-latency somatosensory evoked potentials in
      normal aging and dementia.
AB  - Middle-latency somatosensory evoked potentials (MLSEPs) were recorded in four
      groups of subjects: 13 normal young controls (mean age, 17.9 years). 11 normal
      elderly (mean age, 66.9 years), 11 patients with dementia of Alzheimer's type
      (DAT: mean age, 70.5), and four with vascular dementia (mean age, 79.3). MLSEPs
      in normal elderly showed an increase in the latency of P22, N30, P45, N60, and
      P100, and in the amplitude of N60. DAT patients also presented such changes;
      however, the increase in the amplitude of N60 was much more evident than that
      found in normal aging and was accompanied by a significant increase in amplitude
      of P45. Patients with vascular dementia tended to show longer latencies and
      larger amplitudes than the other groups. The increase in amplitude of P45 and N60
      in MLSEPs seems to be characteristically associated with normal aging and the
      development of dementia. It is suggested that the mechanism of such functional
      changes might be correlated with the structural and neurochemical changes
      accompanying neuronal loss in these conditions.

PMID- 8987048
TI  - Age-and height-dependent changes of amplitude and latency of somatosensory evoked
      potentials in children and young adults with Down's syndrome.
AB  - Middle-latency somatosensory evoked potentials (MLSEPs) were recorded from 19
      scalp electrodes in 34 patients with Down's syndrome (DS) aged 7.4 to 35.7 years
      and in 16 normal control subjects aged 6.4 to 34.4 years. DS patients showed an
      increase in amplitude of P22, P45, and N60. P100 latency was significantly
      shortened. After normalization for height of subjects, N20 and N60 latencies were
      significantly longer in the patient group than in control subjects. On the other
      hand, it was possible to observe in both groups a significant trend for MLSEP
      amplitudes to decrease with age during the age period considered in this work.
      This study further confirms that the pattern of increase in amplitude of MLSEP
      components observed in DS is a finding peculiar of this syndrome and is not
      correlated with early aging processes.

PMID- 8987049
TI  - "One-way asynchrony' of burst-suppression activity.
AB  - In a patient with traumatic intracerebral lesions, we recorded two subsequent
      electroencephalograms with burst-suppression activity. Between the two
      measurements, the clinical condition of the patient deteriorated. The first EEG
      showed symmetrical interhemispheric asynchrony of bursts. In the second EEG,
      however, we noted synchrony from one hemisphere to the other, but asynchrony in
      the opposite direction. We propose a simple model that can explain why one-way
      asynchrony of burst-suppression activity is prognostically more severe than
      symmetrical asynchrony.

PMID- 8987050
TI  - EEG findings in acetazolamide-responsive hereditary paroxysmal ataxia.
AB  - EEG studies were performed in six family members affected by acetazolamide
      responsive paroxysmal ataxia. Intermittent rhythmic delta activity was found at
      rest in five of them; low amplitude spikes were associated with delta waves in
      two cases, resulting in irregular spike and wave patterns. Slowing of background
      activity was present in three patients. EEG abnormalities were activated by
      hyperventilation and modified neither by intermittent photic stimulation, nor by
      acetazolamide therapy. Our results suggest that EEG may be helpful to recognize
      this rare, but well defined, treatable disorder.

PMID- 8987051
TI  - Erythema nodosum in children: a study of 27 patients.
AB  - Erythema nodosum (EN) seems to occur in children more rarely than in adults. It
      still remains the most frequent acute panniculitis, for which the diagnosis is
      almost always clinical. In a retrospective study of 27 pediatric patients, we
      have attempted to clarify the clinical spectrum and prognosis of this disease and
      discuss the differential diagnosis of nodular eruptions on the lower limbs of
      children. In almost half the patients of our series, the cause of EN remained
      undetermined. Streptococcal infections (usually of the pharynx) were the most
      common cause of EN in children (22% of patients in our series), followed by
      Yersinia infection in about 15% of patients. Tuberculosis, an important cause in
      the past, was never found, but must always be excluded. A benign course was noted
      in all patients. Erythema nodosum is easily recognized clinically, but other
      subcutaneous lesions, especially nodular vasculitis and Schonlein-Henoch purpura,
      have to be excluded by pathologic study, in cases of atypical presentation or
      long duration.

PMID- 8987052
TI  - Disseminated cutaneous eruption after BCG vaccination.
AB  - We present nine infants (3 to 10 months of age) with numerous small, papular,
      papular-lichenoid, and papulo-pustular lesions predominantly on the upper and
      lower limbs associated with local (axillary) lymphadenopathy which appeared after
      BCG vaccination. Histopathology of the lesions showed small tuberculoid
      granulomas mainly in the papillary dermis. The presence of BCG bacillus was
      demonstrated in five out of seven samples from the lymph nodes after culture and
      in one skin biopsy specimen. All cases, whether treated or not, evolved to
      complete resolution of the skin lesions. We believe that this peculiar
      association results from hematogenous spread of the bacillus, which regresses
      after an adequate immune system reaction.

PMID- 8987053
TI  - Tegumentary leishmaniasis in childhood.
AB  - Very little has been published about tegumentary leishmaniasis in children and
      there are many controversies about this disorder in the literature. Therefore, we
      discuss the pathogenesis, clinical aspects, means to diagnosis, and treatment of
      this endemic disease.

PMID- 8987054
TI  - Mechanical properties of skin in Ehlers-Danlos syndrome, types I, II, and III.
AB  - Mechanical properties of skin were evaluated in vivo in 17 children suffering
      from Ehlers-Danlos syndrome (EDS) types I, II, and III. These were compared with
      normal values from 63 healthy children. Noninvasive measurements were performed
      under suction of 500 mbar using a Cutometer equipped with a 4-mm probe. Prominent
      increases in skin extensibility and elasticity were the most distinctive and
      diagnostic features of all three EDS types. Differences in the average values of
      biomechanical variables were present among the three types. Patients with EDS-I
      were the most affected, whereas those with EDS-III had virtually normal skin.
      However, interindividual differences in the severity of rheological alterations
      were found within each type, illustrating a continuum in the variation of
      mechanical properties of EDS skin rather than yielding step differences among the
      types.

PMID- 8987055
TI  - Malignant rhabdoid tumor presenting as a hemangioma.
AB  - Malignant rhabdoid tumor is a rare and highly aggressive malignancy of unknown
      etiology. We report a primary cutaneous rhabdoid tumor on the upper back of a
      newborn. It was initially diagnosed as a hemangioma clinically, and that
      diagnosis was supported by radiologic studies, including magnetic resonance
      imaging. However, detailed investigation with light microscopy,
      immunohistochemistry, and electron microscopy enabled us to make a diagnosis of
      rhabdoid tumor. This is the seventh reported case of rhabdoid tumor with primary
      cutaneous involvement.

PMID- 8987056
TI  - Congenital leukemia cutis preceding monoblastic leukemia by 3 months.
AB  - We report an infant born with a cutaneous nodular eruption and neutropenia. Skin
      biopsy specimens revealed an immature dermal infiltrate suggestive of leukemia
      cutis, but repeated peripheral blood and bone marrow examinations failed to
      demonstrate malignant cells. The eruption resolved spontaneously. At the age of 3
      months, a second occurrence of maculopapular skin lesions led to discovery of an
      acute monoblastic leukemia with (9;11)(p21-22;q23) translocation. Congenital
      acute leukemia is a rare disease associated with skin infiltration in 25% to 30%
      of patients. Usually the diagnosis is easily made by peripheral blood examination
      and/or bone marrow aspirate. However, skin involvement may precede acute leukemia
      by several weeks. Although very rare, this event must be kept in mind.

PMID- 8987057
TI  - Partial lipodystrophy associated with juvenile dermatomyositis: report of two
      cases.
AB  - A 27-year-old woman and a 13-year-old girl diagnosed with juvenile
      dermatomyositis in childhood developed clinical findings of partial lipodystrophy
      10 years after diagnosis. Exhaustive clinical and laboratory examinations showed
      an association with other abnormalities: hypertrichosis, steatohepatitis, and an
      abnormal insulin response to the glucose loading test in the first patient.
      Hypertrichosis, steatohepatitis, insulin-resistant diabetes mellitus, and
      acanthosis nigricans were observed in the second patient. Renal function was
      normal in both patients. Although a localized form of lipodystrophy has been
      reported associated with connective tissue disease (connective tissue
      lipoatrophy), the partial form has been infrequently described in association
      with juvenile dermatomyositis.

PMID- 8987058
TI  - Chronic meningococcemia in childhood: case report and review of the literature.
AB  - Chronic meningococcemia is a rare form of meningococcal infection. Most reported
      cases occur in adults. Only about 10% of reported patients are under 18 years of
      age. We herein report chronic meningococcemia in a 17-month-old immunocompetent
      child and review the literature. Our patient had a 4-month history of several
      episodes of intermittent fever accompanied by widespread erythematous and
      purpuric, crusted papules and pustules with necrotic centers. Blood cultures were
      positive for group C Neisseria meningitidis. Histopathology of a skin biopsy
      specimen revealed leukocytoclastic vasculitis. Because the disease is uncommon
      and can be confused with other conditions including other infectious processes,
      vasculitis, and collagen vascular diseases, it is important to have a high degree
      of suspicion for chronic meningococcemia. This will help avoid a delayed
      diagnosis and/or inappropriate treatment. The positive blood culture remains the
      diagnostic sine qua non. Treatment with ceftriaxone was rapidly successful in our
      patient.

PMID- 8987059
TI  - Trichophyton rubrum infection in a 3-day-old neonate.

PMID- 8987060
TI  - Trichostasis spinulosa: a clinical simulant of acne open comedones.
AB  - Trichostasis spinulosa is a disorder of the pilosebaceous follicles that may
      simulate acne open comedones. It is a commonly reported cosmetic annoyance in
      adults but not children. A review of the literature and a case of trichostasis
      spinulosa in a 13-year-old black girl with a history of onset at 18 months of age
      are presented.

PMID- 8987061
TI  - Successful treatment of onychomycosis with fluconazole in two patients with
      hyperimmunoglobulin E syndrome.
AB  - We report two patients with hyperimmunoglobulin E syndrome who had fingernail
      onychomycosis and were successfully treated with fluconazole. Relapse of oral
      candidiasis, but not of onychomycosis, was observed within three months of
      stopping fluconazole. There were no adverse effects from this therapy. Based on
      our experience, we think that fluconazole may be useful in the treatment of
      onychomycosis in patients with hyper-IgE syndrome as well as in those with other
      primary immunodeficiency disorders.

PMID- 8987062
TI  - Treatment of childhood cutaneous T-cell lymphoma with alpha-interferon plus PUVA.
AB  - All forms of cutaneous T-cell lymphoma are rare in childhood. We describe an 8
      year-old boy with plaque-stage mycosis fungoides stage IIA whose cutaneous
      eruption had been present for 5 years. Histologic examination revealed the
      presence of a granulomatous infiltrate together with atypical lymphocytes within
      the dermis. The child had an excellent response to combination psoralen-UVA
      (PUVA) with interferon-alpha 2a treatment and is currently in remission.

PMID- 8987063
TI  - Lymphomatoid papulosis: successful weekly pulse superpotent topical
      corticosteroid therapy in three pediatric patients.
AB  - Lymphomatoid papulosis is a T-cell proliferation that occurs primarily in adults
      but has been well described in children. Lesions may regress spontaneously but
      often leave residual scarring and, as a result, intervention frequently is
      considered. Therapeutic modalities commonly employed for adults with lymphomatoid
      papulosis may be poorly tolerated by pediatric patients. We present a series of
      three children with lymphomatoid papulosis treated with superpotent topical
      corticosteroids (halobetasol or clobetasol propionate). When applied twice daily
      for 2 to 3 weeks followed by weekly pulsed application, this treatment resulted
      in complete resolution of nearly all cutaneous lesions. Three ulcerated lesions,
      occurring in two patients, required adjuvant therapy with intralesional
      triamcinolone. To date one patient remains free of cutaneous disease and two
      children experience occasional new lesions that respond to renewed treatment with
      topical clobetasol propionate. None of the children have evidence of systemic
      disease. We conclude that pulsed application of a superpotent topical
      corticosteroid is efficacious and safe in the management of cutaneous lesions of
      lymphomatoid papulosis and avoids the risks often associated with more aggressive
      interventions. Since these agents do not alter the risk of subsequent malignancy,
      careful ongoing surveillance of children with lymphomatoid papulosis is
      imperative.

PMID- 8987064
TI  - What syndrome is this? Branchio-oto-renal syndrome.

PMID- 8987065
TI  - An acute generalized bullous eruption in a young girl.

PMID- 8987066
TI  - A 3-day rate of efficacy of a moderate potency topical steroid in the treatment
      of atopic dermatitis in infancy and childhood.

PMID- 8987067
TI  - Childhood granulomatous periorificial dermatitis.

PMID- 8987068
TI  - Oral controlled release technology for peptides: status and future prospects.
AB  - In spite of significant efforts in academic and commercial laboratories, major
      breakthroughs in oral peptide and protein formulation have not been achieved. The
      major barriers to developing oral formulations for peptides and proteins include
      poor intrinsic permeability, lumenal and cellular enzymatic degradation, rapid
      clearance, and chemical and conformational stability. Pharmaceutical approaches
      to address these barriers, which have been successful with traditional, small,
      organic drug molecules, have not readily translated into effective peptide and
      protein formulations. The success achieved by Sandoz with cyclosporin
      formulations remains one clear example of what can be achieved, although it is
      likely that effective oral formulations for peptides and proteins will remain
      highly compound specific. Although the challenges are significant, the potential
      therapeutic benefit remains high, particularly with the increasing identification
      of potential peptide and protein drug candidates emerging from the biotechnology
      arena. Successful formulations will most likely require a systematic and careful
      merger of formulation and design delivery systems which maximize the potential
      for absorption across the epithelial cell layer.

PMID- 8987069
TI  - Current status and future prospects of transdermal drug delivery.

PMID- 8987070
TI  - Biocompatibility issues of implantable drug delivery systems.

PMID- 8987072
TI  - Characterization of lipid membrane dynamics by simulation: 3. Probing molecular
      transport across the phospholipid bilayer.
AB  - PURPOSE: The goal of this study is to elucidate the role of the motions of the
      hydrocarbon chains of a phospholipid bilayer in penetrant diffusion. Penetrant
      size, as well as its position in the hydrocarbon core of the lipid bilayer, has
      also been explored regarding impact on the diffusion rate in a phospholipid
      bilayer. METHOD: Molecular dynamics, MD, simulations were carried out on a model
      dimyristoyl phosphatidylcholine (DMPC) membrane bilayer with and without methanol
      and propanol as penetrants. The MD trajectories were analyzed in terms of
      estimating time and space properties. RESULTS: These simulations show that
      torsion angle kink shifts in the hydrocarbon chains of phospholipids are natural
      occurrences in a bilayer assembly. The diffusion coefficients of methanol and
      propanol in a DMPC lipid bilayer, as calculated from the MD simulations, agree
      with experimental measurements. Both methanol and propanol show different
      diffusion rates in different regions of the hydrocarbon chain matrix of the lipid
      bilayer. Solute size has more impact on diffusion rate in the bilayer regions
      with high torsion angle order parameters, as compared to the regions with low
      torsion angle order parameters. CONCLUSIONS: The simulated transport behavior
      suggests that a kink shift diffusion mechanism is more likely to occur in regions
      with high torsion angle order parameters, and a free volume transport mechanism
      is more likely operative in the region with low torsion angle order parameters,
      mainly the center core of the bilayer. A three zone diffusion model is proposed
      for transport of a penetrant across a bilayer.

PMID- 8987073
TI  - Guidance in the setting of drug particle size specifications to minimize
      variability in absorption.
AB  - PURPOSE: To provide guidance in setting particle size specifications for poorly
      soluble drugs to minimize variability in absorption. METHODS: A previously
      reported computer method was used to simulate the percent of dose absorbed as a
      function of solubility, absorption rate constant, dose, and particle size.
      RESULTS: The simulated percent of dose absorbed was tabulated over a realistic
      range of solubilities, absorption rate constants, and doses using drug particle
      sizes that might be typically found in a dosage form. CONCLUSIONS: The greatest
      effect of particle size on absorption was simulated for low dose- low solubility
      drugs. In general, the sensitivity of absorption to particle size decreased with
      increasing dose or solubility. At a solubility of 1 mg/mL, particle size had
      practically no effect on the percent of dose absorbed over the range of doses
      simulated (1-250 mg).

PMID- 8987074
TI  - In-vitro dissolution profile comparison: statistics and analysis, model dependent
      approach.
AB  - PURPOSE: To develop and propose a "model dependent' approach for the in-vitro
      dissolution profiles comparison. METHODS: Diltiazem hydrochloride tablet
      dissolution profiles were compared using a statistical approach based on a
      mathematical model. A similarity region (SR) was defined based on the intra- and
      inter-lot parameter variances of the final production size standard lots.
      Statistical distances between the test and reference lot parameter means were
      computed and normalized. A 90% confidence region (CR) was developed around the
      statistical distance. The confidence region was compared with the similarity
      region to assess the similarity or dis-similarity of the test and reference (REF)
      lot dissolution profiles. Two test lots, one with a "minor' modification (mm) the
      other with a "major' modification (MM), were evaluated. RESULTS: "Weibull' was
      selected as the "model' function. A comparison of the confidence regions around
      the statistical distance of "mm-REF' and "MM-REF' with the similarity region,
      suggested that the dissolution profiles of the "minor' modification lot were
      similar and that of "major' modification lot were dis-similar to the reference
      lot. CONCLUSIONS: A "model dependent' approach was shown to be useful for the
      inter-lot in-vitro dissolution profiles comparison.

PMID- 8987071
TI  - Drug delivery issues in vaccine development.
AB  - Although significant headway has been made in vaccine development, there are
      several delivery-related issues that must be overcome to advance tomorrow's
      candidate vaccines. Some of these are in the areas of: single-shot subunit
      vaccines, therapeutic vaccines for cancer, the use of cytokines as vaccine
      adjuvants, DNA-based vaccines, and the development of vaccines that provide
      sterilizing immunity, as might be required for an affective HIV-1 prophylactic
      vaccine. The hurdles for vaccine advancement in these areas are briefly
      described.

PMID- 8987075
TI  - Feasibility of effect-controlled clinical trials of drugs with pharmacodynamic
      hysteresis using sparse data.
AB  - PURPOSE: To explore, by simulation procedures, the feasibility of characterizing,
      from sparse data, the concentration-effect relationship of drugs with
      pharmacodynamic hysteresis. METHODS: For computer simulations, the concentration
      effect relationship was assumed to be describable by the Sigmoid-Emax equation,
      the site of drug action was located in a distinct effect compartment (keo = 10 x
      kelim), and the pharmacokinetics were those of either a linear one- or two
      compartment system. In view of the poor estimability of the parameters of the
      Sigmoid-Emax model under the usual clinical conditions, central compartment post
      distributive drug concentrations required to elicit various intensities of effect
      within the therapeutic range were used as data descriptors. Effect intensities of
      5 and 25, or 25 and 50 units (with the "unknown" Emax = 100 units) were targeted
      in multiple-dose (steady state) trial designs. From these data, drug
      concentrations required to produce effect intensities of 15 and 50 units were
      estimated by both log-linear and linear interpolation and the actual effect
      intensities produced by these concentrations were calculated. These simulations
      were performed over a wide range of Hill coefficient values (0.5 to 4.0) and
      dosing intervals (0.1 to 1.5 x elimination t1/2. RESULTS: Acceptable results
      could be obtained by measuring drug concentrations and effect intensities at or
      near the end of a dosing interval. The largest deviations of effective
      concentration estimates (in terms of effect intensity) occurred at a Hill
      coefficient value of 0.5 and the results were very little affected by changing
      the dosing interval. CONCLUSIONS: Our results demonstrate that effect-controlled
      clinical trials, with sparse data, of drugs with pharmacodynamic hysteresis for
      determining concentration-effect relationship in the therapeutic range are
      feasible in principle.

PMID- 8987076
TI  - Characterization of a solid state reaction product from a lyophilized formulation
      of a cyclic heptapeptide. A novel example of an excipient-induced oxidation.
AB  - PURPOSE: To elucidate the structure of a degradation product arising from a
      lyophilized formulation of a cyclic heptapeptide, and to provide a mechanism to
      account for its formation. METHODS: Preparative HPLC was used to isolate the
      degradate in quantities sufficient for structural studies. A structure assignment
      was made on the basis of the compounds spectroscopic properties (UV, MS, NMR) and
      the results of amino acid analysis. RESULTS: The degradate was identified as a
      benzaldehyde derivative arising from the oxidative deamination of an aminomethyl
      phenylalanine moiety. The extent of formation of this product is influenced by
      the amount of mannitol used as an excipient in the formulation. A mechanism is
      proposed whereby reducing sugar impurities in mannitol act as an oxidizing agent
      via the intermediacy of Schiff base adducts which subsequently undergo
      tautomerization and hydrolysis. CONCLUSIONS: Reducing sugar impurities in
      mannitol are responsible for the oxidative degradation of the peptide via a
      mechanism that involves Schiff base intermediates. This mechanism may be a
      potential route of degradation of other arylmethyl amines in mannitol-based
      formulations.

PMID- 8987077
TI  - Degradation kinetics of DMP 777, an elastase inhibitor.
AB  - PURPOSE: The objective was to evaluate the degradation profile of the elastase
      inhibitor DMP 777 and lay the foundation for formulation development. METHODS:
      The pKa was determined by potentiometric titration in mixed-aqueous solvents. The
      degradation kinetics were studied as a function of pH, buffer concentration,
      ionic strength, methanol concentration and temperature using a stability
      indicating HPLC assay. The degradation products were identified by LC-MS, NMR,
      and by comparison with authentic samples. RESULTS: The pKa for the protonated
      piperazine nitrogen was estimated to be 7.04. The pH-rate profile is described by
      specific acid-, water-, and specific base-catalyzed pathways. The pH of maximum
      stability is in the range of 4 to 4.5 where water is the principal catalyst in
      the reaction. Buffer catalysis, primary salt effects and medium effects were
      observed. The proposed mechanism for acid catalyzed degradation is the rarely
      observed AAL1 which involves alkyl-nitrogen heterolysis. The driving force for
      the reaction appears to lie in the stability of the benzylic carbocation. The
      proposed mechanism for base catalyzed degradation is BAC2 which involves beta
      lactam ring opening. The beta-lactam ring of DMP 777, a monolactam, appears to be
      as reactive as that in benzylpenicillin in the KOH controlled region where a
      similar mechanism of hydrolysis should be operative. A contributing factor to
      this increased reactivity may lie in the reduced basicity of the beta-lactam
      nitrogen making it a good leaving group. CONCLUSIONS: The degradation profile
      indicates that development of a solution dosage form of DMP 777 with adequate
      shelf-life stability at room temperature is feasible.

PMID- 8987078
TI  - Chemical and swelling evaluations of amino group crosslinking in gelatin and
      modified gelatin matrices.
AB  - PURPOSE: To determine the extent of amino group crosslinking in gelatin matrices
      by chemical assay, and to compare these results to crosslinking evaluations from
      swelling measurements. METHODS: Matrices crosslinked with a water soluble
      carbodiimide (EDC/G), glutaraldehyde (GTA/G), as well as a GTA crosslinked matrix
      prepared from gelatin modified to contain 230% greater crosslinking sites
      (GTA/Mod) were evaluated. Crosslinking extent, Xc, was determined by a UV assay
      of uncrosslinked amino groups before and after crosslinking, and was used to
      obtain crosslinking densities. Equilibrium swelling ratios, Qm, at 37 degrees C
      in isotonic pH 7.4 were used to calculate crosslinking degree from the Flory
      equation for swelling of ionic polymers for comparison to the chemically
      determined crosslinking densities. RESULTS: Of the original 33 x 10(-5) moles
      epsilon-amino groups/g gelatin, 91 to 95% were crosslinked in EDC/G and GTA/G.
      GTA/Mod lost 95% of the original 108 x 10(-5) moles amino groups/g gelatin.
      Crosslinking densities were 4.1 x 10(-4) and 4.2 x 10(-4) moles/mL for EDC/G and
      GTA/G, respectively. The value for GTA/Mod increased to 14.2 x 10(-4) moles/mL.
      Values of Qm followed the same trend. The Flory crosslinking degrees for both
      gelatin matrices were 12 x 10(-4) and 13 x 10(-4) moles/mL, respectively. The
      value for the more extensively crosslinked GTA/Mod was 280 x 10(-4) moles/mL.
      CONCLUSIONS: The swelling and chemical evaluations of crosslinking are in general
      agreement for matrices with the lower of two crosslinking levels. The chemical
      determination appears suitable for evaluating amino group crosslinking in gelatin
      and it may be suitable for other proteinaceous materials.

PMID- 8987079
TI  - Stereoselective and carrier-mediated transport of monocarboxylic acids across
      Caco-2 cells.
AB  - PURPOSE: To characterize the transport mechanism of monocarboxylic acids across
      intestinal epithelial cells by examining the stereoselectivity of the
      transcellular transport of several chiral monocarboxylic acids. METHODS: The
      transport of monocarboxylic acids was examined using monolayers of human
      adenocarcinoma cell line, Caco-2 cells. RESULTS: The permeability of L
      [14C]lactic acid at a tracer concentration (1 microM) exhibited pH- and
      concentration-dependencies and was significantly greater than that of the D
      isomer. The permeabilities of both L-/D-[14C]lactic acids involve saturable and
      nonsaturable processes; the saturable process showed a higher affinity and a
      lower capacity for L-lactic acid compared with the D-isomer, while no difference
      between the isomers was seen for the nonsaturable process. The transport of L
      lactic acid was inhibited by chiral monocarboxylic acids such as (R)/ (S)
      mandelic acids and (R)/(S)-ibuprofen in a stereoselective manner. Mutually
      competitive inhibition was observed between L-lactic acid and (S)-mandelic acid.
      CONCLUSIONS: Some chiral monocarboxylic acids are transported across the
      intestinal epithelial cells in a stereoselective manner by the specific carrier
      mediated transport mechanism.

PMID- 8987080
TI  - Biliary excretion of glycyrrhizin in rats: kinetic basis for multiplicity in bile
      canalicular transport of organic anions.
AB  - PURPOSE: To examine the presence of multiplicity for the biliary excretion of
      xenobiotic conjugates, we studied the disposition of glycyrrhizin (GR), which has
      glucuronide within its molecular structure and has the ability to inhibit the
      biliary excretion of liquiritigenin (LG) glucuronides. METHODS: GR was
      administered intravenously as a bolus to Sprague-Dawley (SD) rats which received
      an i.v. infusion of inhibitors (dibromosulfophthalein (DBSP) and indocyanine
      green (ICG)) at their transport maximum rates. Biliary excretion of GR was also
      examined in Eisai hyperbilirubinemic rats (EHBR), which have a hereditary defect
      in the canalicular transport system of several organic anions. RESULTS: Infusion
      of ICG did not affect the biliary excretion of GR, whereas infusion of DBSP
      reduced it significantly. The plasma concentration of GR was increased by DBSP
      but not by ICG. In EHBR, the biliary excretion of GR was severely impaired,
      resulting in an increase in the plasma concentration of GR. CONCLUSIONS: These
      findings suggest (1) that the biliary excretion of GR is mediated by the system
      which is shared by DBSP and LG glucuronides but not by ICG and (2) that this
      system is hereditarily defective in EHBR. Together with our previous findings,
      the multiplicity for the biliary excretion of organic anions is shown.

PMID- 8987081
TI  - Gastrointestinal uptake of biodegradable microparticles: effect of particle size.
AB  - PURPOSE: To investigate the effect of microparticle size on gastrointestinal
      tissue uptake. METHODS: Biodegradable microparticles of various sizes using
      polylactic polyglycolic acid (50:50) co-polymer (100 nm, 500 nm, 1 micron, and 10
      microns) and bovine serum albumin as a model protein were formulated by water-in
      oil-in-water emulsion solvent evaporation technique. The uptake of microparticles
      was studied in rat in situ intestinal loop model and quantitatively analyzed for
      efficiency of uptake. RESULTS: In general, the efficiency of uptake of 100 nm
      size particles by the intestinal tissue was 15-250 fold higher compared to larger
      size microparticles. The efficiency of uptake was dependent on the type of
      tissue, such as Peyer's patch and non patch as well as on the location of the
      tissue collected i.e. duodenum or ileum. Depending on the size of microparticles,
      the Peyer's patch tissue had 2-200 fold higher uptake of particles than the non
      patch tissue collected from the same region of the intestine. Histological
      evaluation of the tissue sections demonstrated that 100 nm particles were
      diffused throughout the submucosal layers while the larger size
      nano/microparticles were predominantly localized in the epithelial lining of the
      tissue. CONCLUSIONS: There is a microparticle size dependent exclusion phenomena
      in the gastrointestinal mucosal tissue with 100 nm size particles showing
      significantly greater tissue uptake. This has important implications in designing
      of nanoparticle-based oral drug delivery systems, such as an oral vaccine system.

PMID- 8987082
TI  - Liver targeting of interferon through pullulan conjugation.
AB  - PURPOSE: The purpose of this study was to actively target interferon (IFN) to the
      liver through its chemical conjugation with pullulan, a water-soluble
      polysaccharide with a high affinity for the liver. METHODS: Chemical conjugation
      of IFN with pullulan was achieved by a cyanuric chloride method. Following
      intravenous injection of the conjugates to mice, their body distribution and the
      activity of an IFN-induced enzyme, 2', 5'-oligoadenylate (2-5A) synthetase in the
      liver and other organs, were evaluated. RESULTS: The cyanuric chloride method
      enabled us to prepare an IFN-pullulan conjugate that retained approximately 7-9%
      of the biological activity of IFN. Pullulan conjugation enhanced the liver
      accumulation of IFN and the retention period with the results being reproducible.
      When injected intravenously to mice, the IFN-pullulan conjugate enhanced the
      activity of 2-5A synthetase in the liver. The activity could be induced at IFN
      doses much lower than those of free IFN injection. In addition, the liver 2-5A
      synthetase induced by conjugate injection was retained for 3 days, whereas it was
      lost within the first day for the free IFN-injected mice. CONCLUSIONS: IFN
      pullulan conjugation was promising for IFN targeting to the liver with efficient
      exertion of its antiviral activity therein.

PMID- 8987083
TI  - The pH-dependence in the partitioning behaviour of (RS)-[3H]propranolol between
      MDCK cell lipid vesicles and buffer.
AB  - PURPOSE: The pH-dependent partitioning of (RS)-[3H]propranolol between
      unilamellar vesicles of MDCK cell lipids and buffer was determined. METHODS:
      Partitioning studies were performed by means of equilibrium dialysis at 37
      degrees C between pH 7 and 11 at a molar propranolol/lipid ratio in the membrane
      of 10(-6). RESULTS: The partition-pH diagram was bell-shaped. The highest
      apparent partition coefficient was 1797 at pH 9.7, the lowest was 805 at pH 6.9.
      Curve fitting with a combination of Henderson-Hasselbalch equations revealed an
      inflection point at the apparent pKa of propranolol, i.e. 9.7, and two additional
      pKa values at pH 7.7 and 10.0. The first one corresponds to the pKa of free fatty
      acids (FFA) within lipid bilayers and the other one to the pKa of
      phosphatidylethanolamine (PhE). The true partition coefficients (P) of the
      neutral as well as the ionised solute were fitted for each ionisation status of
      the membrane. The highest P, i.e. 2123, was calculated for neutral propranolol in
      the membrane with deprotonated FFA and protonated PhE. CONCLUSIONS: The
      partitioning behaviour of (RS)-[3H]propranolol in a complex membrane/buffer
      system can be described when considering ionisation changes of drug and lipids.

PMID- 8987084
TI  - New cationic lipid formulations for gene transfer.
AB  - PURPOSE: To develop appropriate dosage forms of DNA for gene delivery. METHODS: 3
      beta [N-(N', N' dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) was mixed
      either with Tween 80 alone, or with additional lipid components including castor
      oil and phosphatidylcholine (PC) or dioleoylphosphatidylethanolamine (DOPE) to
      make different lipid formulations. The particle size and the physical stability
      of the formulations upon mixing with plasmid DNA containing the luciferase cDNA
      were examined using laser light scattering measurement. The transfection activity
      of the DNA/lipid complexes was tested in presence or absence of serum using a
      cell culture system. RESULTS: We demonstrated that many favorable properties as a
      gene carrier could be achieved by formulating DNA into new dosage forms using
      Tween 80 as the major emulsifier. Compared to the cationic liposomes, these new
      formulations transfected different cell lines with an equivalent or higher
      efficiency. Not only are they resistant to serum, but also form stable DNA
      complexes which could be stored for longer periods of time without losing
      transfection activity. CONCLUSIONS: Cationic lipids formulated into different
      lipid formulations using Tween 80 as a surfactant appeared to have more favorable
      physical and biological activities than traditional cationic liposomes as a
      carrier for gene delivery.

PMID- 8987085
TI  - Riboflavin-enhanced transport of serum albumin across the distal pulmonary
      epithelium.
AB  - PURPOSE: Conjugation of bovine serum albumin (BSA) with riboflavin (BSA
      riboflavin) increases its uptake into cultured epithelial cells. Our purpose was
      to determine whether transport of BSA-riboflavin across the intact distal
      pulmonary epithelium is also increased, and whether transcytosis plays a role.
      METHODS: In anesthetized rats, we instilled 3H-BSA-riboflavin or 3H-BSA into the
      trachea and measured their appearance in blood. In isolated, perfused rat lungs
      we measured the distal pulmonary epithelium permeability-surface area product
      (PS) for FITC-BSA or FITC-BSA-riboflavin. RESULTS: In intact rats we found 2.1
      times more 3H-BSA-riboflavin than 3H-BSA appeared in blood 60 min after
      intratracheal instillation of the protein. In isolated, perfused rat lungs we
      found that BSA-riboflavin had double the PS of BSA (2.63 vs. 1.46 x 10(-5)
      cm3/sec). The addition of transcytosis inhibitors monensin or nocodazole (both 3
      x 10(-5) M) reduced the BSA-riboflavin PS to that of BSA and had no effect on the
      PS of unconjugated BSA. Simultaneous measurements of 3H-sucrose PS showed no
      differences in paracellular transport among any of the experimental groups.
      CONCLUSIONS: Conjugation with riboflavin increases the flux of BSA across the
      distal pulmonary epithelium. The increased transport appears to be due to
      transcytosis, which apparently does not play a significant role in the movement
      of unconjugated BSA across the distal pulmonary epithelium.

PMID- 8987086
TI  - Anionic gels as vehicles for electrically-modulated drug delivery. I. Solvent and
      drug transport phenomena.
AB  - PURPOSE: The purpose of this study was to elucidate the in vitro behavior of
      anionic gels as formulation matrices for electrically-modulated drug delivery.
      Agarose and combinations of agarose with other anionic polymers (carbomer 934P;
      xanthan gum) were selected and tested to evaluate their potential for drug
      delivery. METHODS: Electrical current was applied by an automatic crossover power
      supply to minimize the current fluctuation. Hydrocortisone was selected as the
      model drug in order to minimize electrostatic interference with drug transport.
      Syneresis and drug migration were evaluated as a function of current application
      time and the intensity of electrical current. RESULTS: The data show that
      electrical current strength and gellant content can affect both the syneresis and
      drug migration. A linear correlation was found between hydrocortisone loss and
      mass loss via the exudate. Moreover, in agarose-carbomer 934P gel systems,
      cumulative gel mass loss is a linear function of time at low intensities of
      electrical current (e.g., 0.5 mA and 1 mA). However, hydrocortisone distribution,
      after electrical application, is relatively asymmetric in those agarose-carbomer
      934P gels (and in agarose-xanthan gum gels) in contrast to gel matrices
      containing only agarose. CONCLUSIONS: In this study, the use of carbomer 934P in
      conjunction with agarose enables the formulator to achieve zero-order release
      with electrical application. Increased anisotropicity of a gel system due to the
      application of electrical current could alter the effectiveness of a drug
      delivery system.

PMID- 8987087
TI  - A new method for diffusion measurement in polymeric films based on a stacked
      sheet concept.
AB  - PURPOSE: To develop and evaluate a simple, yet well defined, method to measure
      diffusion in semi-solids, i.e. polymeric materials. METHODS: The method was based
      on a concept where equivalent discs of polymeric films were cut and stacked on
      top of each other. The diffusion process was allowed to proceed unidimensionally
      through the stack of films perpendicular to the film surface. After an
      appropriate time, the stack was analysed disc by disc with respect to solute
      content and from the concentration profile so obtained the diffusion coefficient
      was calculated. RESULTS: An all-in-one device was developed, manufactured in
      stainless-steel, that cuts circular discs and stores each one successively in a
      "stack" in the cell compartment. CONCLUSIONS: Data from a silicone based system
      shows that the method, although simple, is accurate and reproducible.

PMID- 8987088
TI  - Deacetylation of diltiazem by several rabbit tissues.
AB  - PURPOSE: Diltiazem (DTZ) undergoes extensive metabolism yielding several
      metabolites, some of which retain a certain degree of pharmacological activity. N
      demethylating activity has been detected mainly in the liver. Nevertheless, the
      organs involved in the formation of the deacetylated metabolite of DTZ (M1) have
      not been fully elucidated. In order to address this issue, we have carried out in
      vitro studies using the blood, lung, brain, small intestine, and liver as enzyme
      sources. METHODS: DTZ (1,000 ng/ml) was incubated in 10,000 x g supernatant
      homogenates of selected tissues or in whole blood for 240 minutes at 37 degrees
      C. Multiple samples were withdrawn, and DTZ and its metabolite M1 were assayed by
      HPLC. RESULTS: The apparent degradation rate constant of DTZ was in the rank
      order blood > lung > brain > liver > small intestine. This trend can also be
      observed for the AUC and for the percentage of DTZ metabolized. In all the tissue
      homogenates examined there was a net production of the deacetylated metabolite.
      The M1 metabolite was also detected in the blood (500 ng/ml after 240 minutes of
      incubation). CONCLUSIONS: The widespread distribution of the DTZ deacetylase
      activity described in this study suggests that extrahepatic metabolism of DTZ to
      M1 may play a relevant role in the overall pharmacokinetics of DTZ.

PMID- 8987089
TI  - Localization of purine metabolizing enzymes in bovine brain microvessel
      endothelial cells: an enzymatic blood-brain barrier for dideoxynucleosides?
AB  - PURPOSE: The specific activities of the purine and pyrimidine metabolizing
      enzymes, purine nucleoside phosphorylase (PNP), adenosine deaminase (ADA) and
      cytidine deaminase (CDA) were determined in bovine brain microvessel endothelial
      cells (BBMECs), whole cerebral tissue and erythrocytes. In addition, the
      substrate specificities (Km and Vmax) of purified calf spleen PNP for inosine and
      2',3'-dideoxyinosine (ddI) and of purified calf intestinal ADA for 2',3'
      dideoxyadenosine (ddA), 6-chloro-2',3'-dideoxypurine (6-Cl-ddP), and 2'-beta
      fluoro-2', 3'-dideoxyadenosine (F-ddA) have been explored. METHODS: BBMECs were
      isolated from bovine cerebral cortex by a two step enzymatic dispersion treatment
      followed by centrifugation over 50% Percoll density gradients. Activities of
      alkaline phosphatase, gamma-glutamyl transpeptidase, ADA, PNP and CDA were
      determined in various tissue homogenates (cerebral cortex, BBMECs and
      erythrocytes). Enzyme kinetic studies were also conducted using commercially
      available enzymes and several nucleoside analogs of interest. RESULTS: The
      activities of ADA and PNP were 42-fold and 247-fold higher in the cerebral
      microvessels than in the cerebral cortex, respectively, while there was no
      detectable CDA activity in the microvessel fraction and very little overall
      activity in the cortex. CONCLUSIONS: ADA and PNP may serve as an enzymatic blood
      brain barrier for some of the anti-HIV dideoxynucleosides. Simulations of brain
      availability for ddI, ddA, 6-Cl-ddP, and F-ddA demonstrated that the quantitative
      significance of enzyme localization may vary dramatically, however, depending on
      the membrane permeability of the drug and its bioconversion rate constant within
      the endothelial cell.

PMID- 8987090
TI  - Different pH dependency of mitomycin C activity in monolayer and three
      dimensional cultures.
AB  - PURPOSE: Previous studies by other investigators have shown an enhancement of
      mitomycin C (MMC) activity at acidic extracellular pH (pHe) in monolayer cultures
      of human cells. The goal of the present study was to determine if the efficacy of
      intravesical MMC therapy in patients treated for superficial bladder cancer can
      be enhanced by using acidified dosing solutions. We evaluated (a) the effect of
      pHe on MMC activity in patient bladder tumors in vitro, and (b) the pH dependency
      of MMC activity in 2-dimensional monolayer and 3-dimensional multilayer cultures
      of human bladder RT4 tumor cells. METHODS: Patient bladder tumors were maintained
      as 3-dimensional histocultures. RT4 cells were harvested and maintained as
      monolayer cultures or as 3-dimensional cell pellets on a collagen gel matrix. The
      cell pellets were 300-450 cell layers and 4,000-5,000 microns in diameter. Tumors
      or cells were incubated for 2 hr with MMC-containing media at pHe of 5, 6, and
      7.4. The drug effect was measured by the inhibition of DNA precursor (thymidine)
      incorporation. The stability of MMC as a function of pHe was determined. About
      24% of MMC was degraded following 2 hr exposure at pHe 5 and < or = 2% at pHe 6
      and 7.4. RESULTS: The drug concentrations required to inhibit thymidine
      incorporation by 50% (IC50) were corrected for the degraded MMC at acidic pHe.
      The results showed no pH-dependent MMC activity in human patient bladder tumors
      nor in RT4 multilayer cultures; the IC50 values were about 10 micrograms/ml at
      all three pHe. In contrast, the monolayer RT4 cultures showed a pH-dependent MMC
      cytotoxicity; the IC50 were 0.1, 0.8 and 1.2 micrograms/ ml at pHe 5, 6 and 7.4,
      respectively (p < 0.05). Pre-incubation of multilayered RT4 cultures in acidic pH
      medium for 8 hr enhanced the MMC activity; the IC50 was reduced by about 5 fold
      at pHe about 3 fold at pHe 6. Similar pH-dependent MMC activity was found when
      multilayers were pre-treated for 1 hr with 0.5 microgram/ml nigericin, a proton
      ionophore known to cause the intracellular pH (pHi) to equilibrate with pHe.
      CONCLUSIONS: These data suggest that the difference in the pH dependency of MMC
      activity in the monolayer and multilayer systems was due to the different
      experimental conditions. The time lag for pHi to equilibrate with pHe in the
      multilayer systems and the instability of MMC at low pHe imply that the efficacy
      of intravesical MMC therapy is unlikely to be enhanced by using acidic dosing
      solution.

PMID- 8987091
TI  - Application of the electrotopological state index to QSAR analysis of flavone
      derivatives as HIV-1 integrase inhibitors.
AB  - PURPOSE: A QSAR study based on electrotopological state (E-state) indices was
      conducted for a series of flavone HIV-1 integrase inhibitors to guide drug
      design. METHODS: E-state indices formulated to encode electronic and topological
      information for each skeletal atom in a molecule (Kier and Hall Pharm. Res. 7:801
      807 (1990)) were calculated using the Molconn-X program, and partial least
      squares (PLS) multivariate regression was used to derive QSAR models. RESULTS:
      Predictive models with correlation coefficients (r2) of 0.98 (3 PLS components)
      and 0.99 (5 PLS components) and corresponding cross-validated correlation
      coefficients (c.v. r2) of 0.51 and 0.73, were obtained for inhibition of cleavage
      and integration, respectively, with one molecule omitted from the analysis.
      CONCLUSIONS: E-state indices at C6, C3', C5', C5, and O4 were found to be more
      important for prediction of activity than those for any of the other 12 flavone
      skeletal atoms that are common to the molecules in the data set.

PMID- 8987093
TI  - Population review of 1995: England and Wales.

PMID- 8987092
TI  - A candidate for cancer gene therapy: MIP-1 alpha gene transfer to an
      adenocarcinoma cell line reduced tumorigenicity and induced protective immunity
      in immunocompetent mice.
AB  - PURPOSE: To evaluate the possibility of cancer gene therapy by the gene delivery
      of chemokine, the effects of human macrophage inflammatory protein 1 alpha (hu
      MIP-1 alpha), murine-macrophage inflammatory protein 1 alpha (mu-MIP-1 alpha),
      and human-interleukin 8 (hu-IL-8) on tumor progression and immunization were
      studied. METHODS: Cachexia-inducing and highly tumorigenic adenocarcinoma cells
      (cell line colon 26, clone 20) were transfected with either a control plasmid, hu
      MIP-1 alpha, mu-MIP-1 alpha, or hu-IL-8 expression vector. The production of hu
      MIP-1 alpha reached > 1.5 ng/ml in vitro when transfectant cells were cultured at
      a cell density of 2 x 10(5) cells in 7 ml for 3 days. Immunocompetent BALB/c mice
      were inoculated into the footpad with the tumor cells, and then primary tumor
      growth, morphological analyses, and tumor immunogenicity were studied. RESULTS:
      The secretion of hu-MIP-1 alpha, mu-MIP-1 alpha, and hu-IL-8 did not affect the
      growth rate in vitro. Reduced tumorigenicities in vivo were observed in
      transfected cells with hu-MIP-1 alpha and mu-MIP-1 alpha. Morphologic observation
      of the site of inoculation of cells transfected with hu-MIP-1 alpha showed
      infiltration of macrophages and neutrophils on the 5th day after the inoculation.
      Mice that had rejected cells transfected with hu-MIP-1 alpha gene were immune to
      a subsequent challenge with the parental cells. CONCLUSIONS: The rejection of the
      cells depends on cytolysis and generates potent and long lasting antitumor
      immunity. These data suggest that tumor cells transfected with the MIP-1 alpha
      gene might be useful as an effective therapy for the treatment of certain tumors.

PMID- 8987094
TI  - Current patterns and trends in male mortality by social class (based on
      occupation).
AB  - Every ten years, information from the decennial census is used together with
      national death registration data to study socio-economic differences in
      mortality. This article reports the findings of one of the analyses prepared for
      the latest decennial supplement. This volume is due for publication late in 1997.
      Over 175,000 deaths of men aged 20-64 in England and Wales were analysed using
      the Registrar General's Social Class (based on occupation) schema. The social
      gradient in all-cause mortality observed in earlier decades is still seen in 1991
      93. In absolute terms, there has been a fall in mortality rates in England and
      Wales over the twenty-year period 1970-72 to 1991-93. This is reflected in the
      falls in mortality rates for each of the social classes I to IV over the two
      decades. In contrast, the mortality rate of Social Class V rose in the early
      1980s. Since then, it has fallen. However, it is still higher than in the early
      1970s. Trends in mortality show a relative widening of social differentials
      developing over this period. This is true for all-cause mortality and for the
      specific causes investigated in this article. Mortality is almost three times
      higher in Social Class V (SMR 189) than in Social Class I (SMR 66). Classes IIIM
      and IV (SMRs 117, 116 respectively) have nearly double the mortality of Class I.
      Even larger differentials are observed for stroke, lung cancer and suicide.

PMID- 8987095
TI  - Mortality trends in the United Kingdom, 1982 to 1992.
AB  - This article examines trends in mortality rates in the United Kingdom over the
      decade 1982 to 1992. Whilst the overall rate of mortality has declined, the
      extent of improvements has varied by sex, age and cause. Male mortality has
      improved slightly more than female mortality over the period, resulting in a
      narrowing of the sex differential. Analyses of mortality by age indicate that the
      greatest improvements have occurred in the 45 and over age group and in the year
      after birth with male mortality at the young adult ages actually increasing over
      the period. Trends in cause of death patterns over the period have also been
      studied, and the impact of these changes on the shape of the mortality curve
      described.

PMID- 8987096
TI  - Mortality trends by cause of death in England and Wales 1980-94: the impact of
      introducing automated cause coding and related changes in 1993.
AB  - This article describes the implementation of a computerised system for coding the
      cause of death from death registrations in England and Wales since the beginning
      of 1993, and the impact this has had on national cause of death statistics.
      Overall the automated system has been effective and reliable at deriving ICD-9
      codes for the underlying cause of death and other conditions mentioned on the
      certificate. Automation increases the consistency and international comparability
      of cause of death coding. However, it has led to discontinuities in time trends
      between 1992 and 1993, which are explored here. The largest effect was related to
      expected changes in the application of ICD-9 selection rule 3. However there were
      other effects which were not expected. The automated system does not deal
      adequately with external causes of death, which are certified after coroner's
      inquest, and ONS has reverted to coding these clerically. Lessons for the
      implementation of ICD-10 for mortality have been learnt.

PMID- 8987098
TI  - Effect of oral supplements of vitamin A on the plasma retinol levels in calves
      and their immunological unresponsiveness.
AB  - Forty calves were used to evaluate the immune response effects induced by a wide
      range of dietary vitamin A intake levels. The immune response was not affected by
      the tested doses of vitamin A administered orally during a 56 day period. There
      was no change in plasma immunoglobulin concentrations and no difference in
      specific antibody titres following injection of keyhole limpet haemocyanin (KLH)
      at 10, 20 and 40 days of age. Some small and temporary variations were recorded
      in the plasma vitamin A concentration following daily oral administration of
      various doses up to 10,000 IU. Only oral supplementation of 20,000 IU of vitamin
      A daily over 50 days significantly increased the plasma level of vitamin A.

PMID- 8987097
TI  - Breakdown of peptides from a casein hydrolysate by rumen bacteria. Simultaneous
      study of enzyme activities and physicochemical parameters.
AB  - The breakdown of a pancreatic hydrolysate of casein (tryptone) by an inoculum of
      ruminal mixed bacteria was studied in vitro. Peptides were degradated at 33%
      after 5 h. The dipeptidyl aminopeptidase type 1 (DAP-1), exoaminopeptidase and
      leucine aminopeptidase (LAP) like activities were measured using, respectively,
      Gly-Arg-MNA, Ala-pNa and Leu-pNA as substrates. While the total proteolytic
      activity remained stable throughout peptide breakdown, the DAP-1 already present
      at the beginning of fermentation increased until two times its early activity.
      This peptidase activity is a major index for the presence of Prevotella
      ruminicola. A peak of exoaminopeptidase and LAP activities were observed at 3 h
      incubation. This latter activity, which was associated with the production of
      lactate after 3 h, suggested that Streptococcus bovis was present in the
      environment. With the use of high-performance size exclusion chromatography
      (HPSEC), the size of the peptides during their breakdown could be measured,
      showing that high molecular weight peptides (4 to 2 kDa) were apparently more
      rapidly broken down to the profit of small-sized peptides (< 0.5 kDa), which
      increased. These degradation abilities were closely linked to DAP-1 activity.
      Separation of tryptone peptides by reverse-phase high-performance liquid
      chromatography (HPLC) showed that more hydrophilic peptides disappeared than
      hydrophobic peptides. Moreover, a few peaks eluting for one in the hydrophilic
      area and for the others in the hydrophobic area resisted the bacterial breakdown.
      In contrast, amino acid profiles indicated that hydrophobic amino acids were not
      taken up significantly faster than the hydrophobic amino acids by mixed ruminal
      bacterial.

PMID- 8987099
TI  - Hybrid ducks overfed with boiled corn develop an acute hepatic steatosis with
      decreased choline and polyunsaturated fatty acid level in phospholipids.
AB  - Hepatic and plasma lipid changes were investigated in hybrid ducks after
      steatosis was induced by overfeeding. Fourteen hybrid ducks were force-fed (11 kg
      corn in 13 days). The liver of the overfed ducks weighed ten times more than that
      of controls (695 vs 69 g). The phospholipid, ash, water and protein content of
      the liver were only slightly higher (2.6-, 3.6-, 4.4- and 3.2-fold, respectively)
      but the liver lipid concentration was 16.5 times higher after than before
      overfeeding (56.1 vs 3.4 g/100 g liver, respectively). Liver phosphatidylcholine
      concentration was higher in the control group (32.4 vs 22.9 mol/100 mol
      phospholipid) revealing a choline deficiency that could contribute to the
      development of liver steatosis. In liver phospholipid, the level of linoleic and
      arachidonic acids were markedly decreased in the overfed ducks, from 5 and 18.1
      to 3.7 and 7.1 mol/100 mol fatty acids, respectively, and were mainly replaced by
      oleic acid. Plasma triacylglycerols increased 5.9-fold, cholesterol 2.2-fold and
      phospholipid 1.6-fold. Heat-induced (50 min at 105 degrees C) fat release, an
      index of poor liver integrity, was particularly high for the large, fat livers
      which contained low levels of phospholipids and phosphatidylcholine.

PMID- 8987100
TI  - A sucrose-DMSO extender for freezing rabbit semen.
AB  - The aim of this study was to define a simple extender for freezing rabbit semen
      from selected males used to inseminate selected doses to obtain embryos for an
      embryo bank. Four experiments were carried out. In the first experiment, freezing
      extender was defined on the basis of the results of the post-thawing motility
      rate. Three factors and their interactions were studied: final concentration of
      dimethyl sulphoxide (DMSO) (1, 1.25, 1.5 and 1.75 M), egg yolk (0% of 10 v/v) and
      sugar (none, or 0.5 M of glucose, lactose, sucrose, or maltose). The sucrose and
      1.75 DMSO improved significantly the post-thawing motility rate (sucrose 1.75 M
      DMSO extender: 42 +/- 3%). In the second experiment, this freezing extender was
      used to freeze semen from three lines. The post-thawing motility and normal
      acrosome rates were similar among the lines when the covariates, fresh motility
      and normal acrosome rates, respectively, were used in the analysis (52 +/- 1 and
      66 +/- 1%, respectively). In the third experiment, frozen semen from the White
      New Zealand line (NZ) was tested by morphological normality and viability of
      embryos recovered. Recovery data from NZ does inseminated with fresh and frozen
      semen were compared. No significant differences were found in the number of
      normal embryos obtained per donor dose (8.9 +/- 0.5) and in their survival after
      vitrification (52% of live foetuses at 29 days of gestation). The sucrose-DMSO
      extender and freezing procedure used in this work can offer satisfactory results
      to apply in conservation and genetic programmes.

PMID- 8987101
TI  - Three year results of in vitro production of bovine embryos in serum-poor bovine
      oviduct conditioned medium. An overview.
AB  - This paper presents a synthesis of 3 year results of in vitro production of
      bovine embryos in medium previously conditioned by bovine oviduct epithelial
      cells. In Louvain-la-Neuve, Belgium, a total of 18356 oocytes were matured and
      inseminated in vitro: 13967 (76%) had cleaved at 3 days post-insemination and
      3593 (26%) became blastocysts using this culture system. Our data show that
      conditioned medium can be stored frozen for up to 3 years without significant
      loss of activity and is resistant to lyophilization. One single batch of
      conditioned medium was tested within the same period in four different
      laboratories and yielded variable results: 27 and 37% blastocysts/cleaved embryos
      in two of them and only 7 and 0% in the two others whereas in each case more than
      30% blastocysts were obtained with the local reference co-culture system. In one
      laboratory, the batch of oil used to overlay the culture drops had a detrimental
      effect on the blastocyst rate in conditioned medium but not in co-culture.

PMID- 8987102
TI  - Effect of indole-3-acetic acid (plant auxin) on the preservation at 15 degrees C
      of boar semen for artificial insemination.
AB  - In order to extend the duration of boar sperm survival at 15 degrees C for
      artificial insemination, we tested the effect of indole-3-acetic acid (IAA),
      which appeared to be the main sperm protective substance present in the Coco
      nucifera endosperm (coconut water). Two IAA concentrations (10 and 100 ng/mL) in
      Beltsville extender (BTS) were studied for their in vitro effects. The motility,
      the percentage of motile spermatozoa and the acrosome morphology of sperm were
      recorded each day over 13 days of storage at 15 degrees C, after 5 min and 3 h of
      incubation at 39 degrees C. The IAA effect on sperm preservation was also studied
      in vivo at a concentration of 10 ng/mL in BTS by inseminating groups of females
      twice at 24 h intervals either at D0 (day of sperm collection) and D1 (D0/1) or
      at D5 and D6 (D5/6). At D0/1, the two groups of females (control and IAA) were
      inseminated with a total of 6.3 x 10(9) spermatozoa (3.15 x 10(9) at D0 and the
      same dose at D1) whereas at D5/6, on IAA group was inseminated with a total of
      6.3 x 10(9) spermatozoa and another one with 12.6 x 10(9) spermatozoa. The
      animals in the D5/6 control group were inseminated each with a total of 12.6 x
      10(9) spermatozoa. For each group of females (n = 106-140), fertility rate (%
      farrowing) and prolificacy rate (litter size) were recorded. No effect of IAA in
      vitro on the motility rate and on the percentage of motile spermatozoa was
      observed over a 13 day storage. However, IAA (10 ng/mL) had a significant
      positive effect on the percentage of living spermatozoa with intact acrosomes
      after 13 days (66 vs 54%, P < 0.05). The fertility and prolificacy rates after 5
      6 days of sperm preservation in BTS extender alone did not differ significantly
      between D5/6 and D0/1 but the total number of inseminated spermatozoa was 12.6 x
      10(9) at D5/6 instead of 6.3 x 10(9) at D0/1. When the spermatozoa were stored in
      the presence of 10 ng/mL IAA for 5-6 days at 15 degrees C, the fertility and
      prolificacy of the females inseminated with only 6.3 x 10(9) spermatozoa were
      identical to those of the females inseminated with an equal number of spermatozoa
      at D0/1 in the presence or absence of IAA.

PMID- 8987103
TI  - Insulin receptors: the binding capacity and localization in the digestive tract
      during the rabbits neonatal period.
AB  - The aim of this study was to localize and measure the receptor-binding capacity
      for insulin in the stomach, duodenum, ileum, jejunum, caecum, colon and in
      isolated hepatocytes in 48 rabbits aged 1-7, 14 and 21 days. Two methods were
      employed: radioimmunoassay (RIA) and receptor-binding assay (RBA). Isolated
      rabbit hepatocytes were used to estimate the maximal binding (Bo). Insulin (INS)
      concentrations measured by RIA-INS test were highest in the colostrum (701
      microU/mL as 100%) of the does, and in the blood (82 microU/mL) of newborn
      rabbits during the first day postpartum. The Bo of colostral insulin for isolated
      hepatocytes was 556 microU/mL, which corresponded to 79.1% of the total binding
      as assessed by the RIA-INS test. The Bo for insulin binding in the different
      parts of the digestive tract tested was the highest on the first day (mean 8.0
      fM/g) and the lowest on the 6th day postnatally (mean 4.9 fM/g; P < 0.01). The
      receptor capacity for insulin varied in relation to the different parts of the
      digestive tract, and with the age of each individual rabbit.

PMID- 8987104
TI  - Influence of increasing breast meat yield on muscle histology and meat quality in
      the chicken.
AB  - The histological characteristics, ie, myofibre types and cross-sectional areas
      (CSA), of pectoralis major and sartorius muscles of 20 male chickens from two
      lines (ten birds from each line) divergently selected for breast meat yield were
      compared. Moreover, some quality parameters (ie, drip loss, ultimate pH value and
      meat colour) of the breast muscle were recorded. The animals from both lines
      displayed identical pectoralis major myofibre types and CSA. A slight difference
      in typology, but not in myofibre CSA, was observed in the sartorius muscle:
      animals with the highest breast meat yield tended to have a more pronounced
      glycolytic character. No significant difference was observed in the quality of
      breast meat (pH, colour and drip loss).

PMID- 8987105
TI  - The ovarian secretion of androstenedione and oestradiol during late pregnancy and
      the early postpartum period in sheep with an autotransplanted ovary.
AB  - During late pregnancy in the ewe, ovarian function is suppressed by placental
      steroids and following parturition ovarian function is restored. This experiment
      determined the ovarian secretion of oestradiol and androstenedione during late
      pregnancy and the early postpartum period in ewes. Six ewes with ovarian
      autotransplants were transplanted with three day 6 embryos and three gave birth
      on day 147. Ovarian and jugular blood sampled were collected on three different
      occasions. On each occasion a 4 h period of sampling was followed by a 6 or 8 h
      period during which the ewes were challenged with 150 ng of gonadotropin
      releasing hormone (GnRH). Basal secretion of oestradiol and androstenedione was
      0.3 +/- 0.1 and 10.5 +/- 3.0 ng min-1, respectively, on day 120 of pregnancy.
      Oestradiol secretion remained low on days 7 and 21 postpartum (0.4 +/- 0.3 and
      0.3 +/- 0.1 ng min-1, respectively). Androstenedione secretion (ng min-1) on days
      7 and 21 postpartum was 2.5 +/- 0.5 and 4.1 +/- 1.8, respectively. The injection
      of GnRH on day 121 of pregnancy produced luteinizing hormone (LH) release with a
      peak concentration of 0.6 +/- 0.1 ng mL-1, that did not stimulate steroid
      secretion. On day 8 postpartum GnRH injection induced LH release with a peak
      concentration of 3.9 +/- 1.1 ng mL-1 that stimulated secretion of oestradiol (0.2
      +/- 0.1 to 2.1 +/- 0.9 ng min-1; P < 0.01) and androstenedione (2.3 +/- 0.6 to
      17.1 +/- 6.9 ng min-1; P < 0.001). Similar effects were seen on day 22
      postpartum; GnRH injection induced LH release with a peak concentration of 4.7 +/
      1.4 ng mL-1 that stimulated secretion of oestradiol (0.2 +/- 0.1 to 3.7 +/- 1.1
      ng min-1; P < 0.001) and androstenedione (4.2 +/- 2.6 to 29.5 +/- 9.2 ng min-1; P
      < 0.01). These results suggest that the suppression of ovarian function during
      late pregnancy in the ewe is reversed by 7 days postpartum.

PMID- 8987106
TI  - Water restriction and bone metabolism in camels.
AB  - 'Krafft disease', occurring in camels living in the very arid areas of North
      Africa, is characterized by spontaneous fractures of costal and/or appendicular
      bones. To better understand the mechanisms of this, we studied the influence of
      water restriction on plasma and urinary markers of bone metabolism in camels.
      Eight 2-year-old nonpregnant, nonlactating camels were studied at the research
      station of Laayoune (Morocco). After a 10 day period of daily watering, five
      animals were watered only every 10th day over a 50 day period, then again watered
      daily for a final 10 day period (rehydration). The three control animals were
      watered daily throughout the whole experimental period (70 days). Each camel was
      fed a ration of straw, luceme hay and barley, resulting in a daily intake of 25 g
      calcium and 11 g phosphorus. Water restriction induced a decrease in daily
      urinary volume and an increase in plasma osmolality. These symptoms of
      dehydration were not associated with any significant change either in the markers
      of osteoblastic activity (plasma alkaline phosphatase activity and osteocalcine
      concentration) or in the markers of bone resorption (urinary excretion of
      calcium, hydroxyproline pyridinoline and deoxypyridinoline). Thus, in well-fed
      camels, water restriction did not affect bone metabolism. However, no conclusions
      were possible regarding the influence of dehydration or calcium and/or phosphorus
      deficiency in the etiology of 'Kraft disease'.

PMID- 8987108
TI  - Morphological abnormalities of rabbit spermatozoa studied by scanning electron
      microscope and quantified by light microscope.
AB  - Rabbit spermatozoa morphological abnormalities were examined to establish
      criteria for judging the quality of ejaculates. Ten New Zealand White bucks, aged
      9 months and weighing 4.3 +/- 0.2 kg, were placed in a climatic chamber for 3
      weeks at +20 degrees C and 70% RH. Sperm was collected three times a week using
      an artificial vagina. The use of a scanning electron microscope (from x 2000 to x
      15,000) in this study produced an illustrated guide for the classification of
      abnormalities. Mean percentage quantitative values studied by light microscope (x
      400) observation were: 18.2% total abnormalities, 2.9% head abnormalities, 13.6%
      tail abnormalities and 1.7% broken spermatozoa. Variability was very high (CV
      35.7, 54.0, 45.3 and 32.5%, respectively); consequently, each ejaculate should be
      analysed before use for artificial insemination. Among the different tail
      abnormalities observed, the most frequent were coiled tails, 9.1%, cytoplasmic
      droplets, 2.4%, bent tails, 1.3% and swollen tails, 0.5%.

PMID- 8987107
TI  - The deleterious effects of human erythropoietin gene driven by the rabbit whey
      acidic protein gene promoter in transgenic rabbits.
AB  - Human erythropoietin (EPO) gene and cDNA associated with the rabbit whey acidic
      protein (WAP) gene promoter were used to tentatively produce the recombinant
      protein in milk of transgenic mice and rabbits. Several gene constructs showed
      good efficiency in the mouse mammary cell line HC11. None of them was able to
      direct the expression of the hormone at a concentration higher than 50
      micrograms/mL in mouse and rabbit milk. With one of the construct, the rabbits
      had an abnormally high amount of red blood cells irrespectively of their sex,
      they could not reproduce and no milk could be obtained from them. These animals
      died prematurely. In these animals, the EPO gene was therefore expressed at a low
      but supraphysiological level in organs other than the mammary gland. These
      experiments show that transgenic animals obtained with gene constructs which do
      not contain insulators cannot be used as living fermentors to produce human
      erythropoietin in their milk at an industrial scale.

PMID- 8987110
TI  - Effect of thiobase incorporation into duplex DNA during the polymerization
      reaction.
AB  - 6-Thioguanine, a thioderivative of the nucleic acid base guanine, is a metabolic
      inhibitor and possesses antitumor activity. In addition, it inhibits the
      synthesis of nucleotides and is incorporated readily into the nucleic acid during
      the polymerization reaction by substituting for guanine. The biological activity
      of 6-thioguanine has been related to the alterations in the dimensions and
      energetics of a duplex DNA as a result its incorporation in place of guanine
      (Bugg and Thewalt 1975). With the advancement in the computer hardware technology
      and emergence of sophisticated molecular modeling packages, it is now possible to
      simulate the biological activities of different drugs. An effort has been made to
      explain the biological activities of thoiderivatives of nucleic acid bases. For
      this, semiempirical MNDO quantum chemical calculations were performed on some non
      complementary (thiosubstituted) base pairs to understand the effects of
      substitution of sulfur for oxygen in nucleic acid bases. The base pairs
      considered in this study are thioguanine-cytosine (TG-C), guanine-thiocytosine (G
      TC) and thioguanine-thiocytosine (TG-TC). The results obtained suggest that the
      replacement of guanine by thioguanine and/or replacement of cytosine by
      thiocytosine weakens the stability of the double helical DNA by reducing the
      strength of the hydrogen bonds.

PMID- 8987109
TI  - Effects of a 33 residue interleukin-1 beta peptide and the antioxidant PQQ on
      interleukin-1 beta-mediated inhibition of glucose-stimulated insulin release from
      cultured mouse pancreatic islets.
AB  - Interleukin-1 beta (IL-1 beta) significantly inhibits insulin secretion from
      glucose stimulated islet cells. The mechanism for this inhibition has been
      hypothesized to be due to stimulation of the inducible form of nitric oxide
      synthase and a resulting increase in nitric oxide (NO) concentration. Ways to
      block the effect of IL-1 beta have focused on blocking the binding of IL-1 beta
      to the IL-1 receptor and the use of antioxidants to neutralize increases in NO.
      This report focuses on a 33 residue peptide synthesized based on the C-terminal
      region of the IL-1 beta molecule, a reported binding site of the IL-1 beta
      molecule, and the redoxcycling antioxidant pyrroloquinoline quinone (PQQ). The 33
      residue peptide did not function as an antagonist, but as a weak agonist. High
      concentrations of PQQ itself inhibited glucose-dependent insulin release while
      low concentrations did not. PQQ had no effect on the actions of IL-1 beta. Three
      isosteric and isomeric analogues of PQQ were also investigated. One of the PQQ
      isomers had an inhibitory effect on insulin secretion at low concentrations where
      PQQ had no effect. These results reflect the sensitivity of islets to oxidative
      stress.

PMID- 8987111
TI  - Rapid induction of hepatocyte growth factor mRNA after administration of gomisin
      A, a lignan component of shizandra fruits.
AB  - Gomisin A (Go), a lignan component of shizandra fruits, protects the liver from
      injury by acetaminophen (AAP). One of its possible mechanisms is supposed to be
      related to the suppression of lipid peroxidation. Since hepatocyte growth factor
      (HGF) was reported to prevent hepatotoxin-induced liver damage, we tested HGF as
      the intermediary of Go effects. Simultaneous analyses of HGF mRNA expression and
      liver histology in rats were performed at 6 and 24 hr after treatment with AAP,
      Go or both. HGF mRNA rapidly expressed at 6 hr after Go treatment, while no HGF
      mRNA was observed at 6 hr after AAP treatment. Induction of HGF mRNA at 24 hr was
      observed after treatment with AAP or AAP plus Go. Histological findings indicate
      that massive necrosis and vacuolization in the liver of rats treated with both
      AAP and Go were reduced in comparison with rats treated with AAP only. These data
      suggest that Go rapidly induces HGF mRNA through different mechanisms from AAP
      induced liver injury.

PMID- 8987112
TI  - Different classes of PAF-antagonists block norepinephrine-induced vascular escape
      and tachyphylaxis in the isolated rabbit kidney.
AB  - In order to study the role of platelet activating factor (PAF) on norepinephrine
      induced vascular escape and tachyphylaxis, compounds from different
      pharmacological families sharing PAF-antagonistic activity, were infused in the
      isolated rabbit kidney perfused with Krebs-Henseleit solution. A natural compound
      derived from Ginkgo biloba (BN 52020, 1.1 x 10(-6) M), a triazolobenzodiazepine
      substance (WEB 2170, 1.1 x 10(-6) M) and a dihydropyridine derivative lacking
      cardiovascular effects (PCA 4248, 2.7 x 10(-6) M), were analysed. The vascular
      reactivity to three cycles of norepinephrine (1.3 x 10(-6) M), infused in the
      kidneys treated with each of the PAF- antagonists, were evaluated for vascular
      escape and tachyphylaxis. The results demonstrated a significant reduction of
      both regulatory phenomena. A fall in renal vascular escape promoted by PAF
      antagonists, from a control level of 50.32 +/- 4.61 to 27.64 +/- 8.01% (p <
      0.05), suggests a role for PAF-acether in the vascular adjustment of the
      mammalian kidney.

PMID- 8987113
TI  - TCDD endrin and lindane induced increases in lipid metabolites in maternal sera
      and amniotic fluids of pregnant C57BL/6J and DBA/2J mice.
AB  - TCDD, endrin and lindane induce an oxidative stress and enhance lipid
      peroxidation in fetal and placental tissues of mice. The levels of the products
      resulting from altered lipid metabolism, including malondialdehyde (MDA),
      formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) have been determined in
      maternal sera and amniotic fluids of pregnant C57BL/6J and DBA/2J mice after oral
      administration of single fetotoxic doses of TCDD, endrin and lindane on day 12 of
      gestation, using high pressure liquid chromatography (HPLC). Under these
      conditions, TCDD given at a dose of 30 micrograms/kg body weight to C57BL/6J mice
      produced 2.5-3.9 and 1.7-4.0 fold increases in the levels of the four metabolites
      in maternal sera and the amniotic fluids, respectively. TCDD given to DBA/2J mice
      at a dose of 60 micrograms/kg produced 1.5-1.7 and 1.7-2.2 fold increases in the
      levels of these metabolites in maternal sera and the amniotic fluids,
      respectively. Endrin, when given at a dose of 4.5 mg/kg body weight to either
      mouse strain, produced increases of 1.9-3.1 and 1.7-3.2-fold in the levels of the
      four metabolites in maternal sera and the amniotic fluids, respectively, in the
      C57BL/6J mice and increases of 1.4-1.6 and 1.2-1.5 fold in the levels of these
      metabolites in maternal sera and the amniotic fluids, respectively, in the DBA/2J
      mice. Lindane given at a dose of 30 mg/kg body weight to C57BL/6J mice produced
      1.5-2.0 and 1.3-1.7-fold increases in the four metabolites in maternal serum and
      amniotic fluids, respectively, while administration of this same dose to DBa/2J
      mice produced 1.2-1.5 and 1.1-1.5 fold increases, respectively. Increases in the
      levels of lipid metabolites occur in maternal serum and amniotic fluid as a
      result of enhanced lipid peroxidation in response to TCDD, endrin and lindane.
      Lipid peroxidation may participate in the fetotoxic effects of these xenobiotics
      and these effects are observed regardless of the Ah-responsiveness of the mice,
      although higher levels of the metabolites are produced by TCDD in Ah-responsive
      mice.

PMID- 8987114
TI  - Determination of a new carbapenem antibiotic, DA-1131, in rat plasma, urine, and
      bile by column-switching high-performance liquid chromatography.
AB  - A column-switching high-performance liquid chromatographic method has been
      developed for the determination of a new carbapenem antibiotic, DA-1131, in rat
      plasma, urine, and bile. Each biological sample was diluted with an equal volume
      of a stabilizer, 3% KH2PO4 (containing 2.0% sodium citrate, adjusted to pH 6.0
      with 10 M NaOH). After centrifugation for 1 min at 3000 g, an aliquot of the
      supernatant was injected directly onto the HPLC column. Deionized water was run
      for 3 min at a flow rate of 1.5 ml/min to retain DA-1131 in an extraction column,
      while proteins and endogenous interferences were eluted to the waste. The analyte
      was then back-flushed onto an analytical column, C18 reversed-phase column. The
      mobile phases for analytical column, 10 mM 3-[N-morpholino]propane sulfonic acid
      (pH 4.5)-acetonitrile (90:10, v/v) for plasma samples, and 5 mM KH2PO4 (adjusted
      to pH 8.0 with 10 M NaOH)-acetonitrile (90:10, v/v) for urine and bile samples,
      were run at a flow rate of 1.0 ml/min. The column effluent was monitored by
      ultraviolet detection at 300 nm. The retention time for DA-1131 was 8 min in
      plasma samples and 13 min for urine and bile samples. The detection limits for DA
      1131 in rat plasma, urine, and bile were 0.05, 1.0, and 1.0 microgram/ml,
      respectively. The intraday and interday coefficients of variation of the assay
      were generally low (below 8.40%) for rat plasma, urine, and bile samples. No
      interference from endogenous substances was observed.

PMID- 8987115
TI  - Pharmacokinetic changes of M1, M2, M3, and M4 after intravenous administration of
      a new anthracycline, DA-125, to alloxan-induced diabetes mellitus rats.
AB  - The pharmacokinetics of M1, M2, M3, and M4 were compared after intravenous (i.v.)
      administration of DA-125, 15 mg/kg to the control (n = 15) and alloxan-induced
      diabetes mellitus (AIDM, n = 11) rats. After i.v. administration of DA-125,
      almost 'constant' plasma concentrations of M1 and M2 were maintained from 1-2 h
      onwards to 8-10 h in both groups of rats due to the continuous formation of M2
      from M1. The plasma concentrations of M3 were the lowest among M1-M4 in the
      control rats due to the rapid and essentially complete conversion of M3 to M4.
      The AUC0-8 h of M1 (189 versus 78.5 mg min/ml) was significantly greater in the
      AIDM rats than that in the control rats. However, the AUCts of M2 (32.7 versus
      44.3 micrograms min/ml) and M4 (not measurable versus 19.7 micrograms min/ml)
      were significantly smaller in the AIDM rats. The renal clearances of both M1
      (0.157 versus 0.334 ml/min/kg) and M2 (0.726 versus 14.6 ml/min/kg) decreased
      significantly in the AIDM rats, presumably due to their impaired kidney function.
      The liver weight decreased significantly in the AIDM rats (2.77 versus 3.77% of
      body weight), suggesting impaired liver function. Above data suggested that the
      metabolism of M1 to M2-M4 in the liver and kidney decreased significantly in the
      AIDM rats. M2 was the main metabolite among M1-M4 excreted in 24 h urine in both
      group of rats. In the AIDM rats, the amount of M2 excreted in 24 h urine
      decreased significantly (15.7 versus 229 micrograms) whereas the amount of M2
      recovered at 24 h from the whole GI tract increased significantly (45.1 versus
      14.0 micrograms).

PMID- 8987116
TI  - Increased cyclic AMP in aortas of cholesterol fed rabbits.
AB  - Cyclic Amp (cAMP) levels were measured in the aortas of rabbits fed a cholesterol
      rich diet for either 24 days (Group I), 86 days (Group II) or 86 days followed by
      54 days of a normal diet (Group III). Aortic levels of cholesterol and
      cholesterol esters, calcium and collagen and noncollagen protein synthetic rates
      were also measured at each time period. Cyclic AMP levels were unchanged in the
      Group I animals but were significantly elevated in Groups II & III. Aortic levels
      of cholesterol and cholesterol esters, calcium and collagen and noncollagen
      protein synthetic rates were also significantly elevated in Groups II & III but
      unchanged in Group I. Since cAMP levels were not changed in Group I animals the
      increase in cAMP appears to be a later, adaptive change in response to the
      feeding of a cholesterol rich diet. The observation that cAMP levels are
      increased in response to cholesterol feeding is important since cAMP is known to
      be involved with a wide range of metabolic functions, which may have a
      significant effect on the development of vascular disease.

PMID- 8987117
TI  - Acetohexamide reductase activities in liver microsomes and cytosol of cisplatin
      treated male rats: cisplatin indirectly modulates the microsomal enzyme activity.
AB  - Treatment with cisplatin, at a dose of 7.2 mg/kg body weight, caused a
      significant decrease of acetohexamide reductase activity in liver microsomes of
      male rats at 4 and 7 days after its treatment; this dose of cisplatin has been
      reported to decrease testosterone levels in serum of male rats. However, the
      treatment with cisplatin could not decrease acetohexamide reductase activity in
      liver cytosol of male rats at the days tested. Although acetohexamide reductase
      activity in liver microsomes of male rats, as described above, was decreased by
      the treatment with cisplatin, the decreased microsomal enzyme activity was nearly
      restored when testosterone propionate was given once daily for 7 days after
      cisplatin treatment. Based on these results, it is reasonable to postulate that
      cisplatin indirectly decreases the microsomal enzyme activity which is regulated
      by androgens, by causing a significant decrease of the testosterone level in
      serum of male rats.

PMID- 8987119
TI  - Effect of aluminum on superoxide dismutase, catalase and lipid peroxidation of
      rat liver.
AB  - Results of the present study suggest that aluminum treatment to rats resulted in
      elevation of microsomal lipid peroxidation along with inhibition of catalase
      activity in the liver. Aluminum treatment to rats has no significant effect on
      rat liver superoxide dismutase activity. A 25% inhibition in catalase activity
      was observed when liver supernatant was incubated with A1C13 at 5 x 10(-3) M
      concentration and above.

PMID- 8987118
TI  - Dithiothreitol tetraacetate S-acetyl esterase activity in different liver
      subcellular fractions and its potential role in the ester-mediated prevention of
      oxidative stress induced cell damage.
AB  - The liver was previously shown to be able to hydrolyze dithiothreitol
      tetraacetate (DTTAC) to dithiothreitol (DTT) via a DTTAC-S-acetyl esterase
      (DTTACEST). In the present studies the intracellular distribution of DTTACEST
      activity and its characteristics are reported. Enzyme specific activity was:
      microsomes > > mitochondria > > nuclei and was absent in the cytosolic fraction.
      The Km of the DTTACEST in each fraction was: mitochondria > microsomes > nuclei
      and the Vmax was microsomes > mitochondria > nuclei. The results were analyzed in
      relation to the previously established antioxidative stress and free radical
      trapping properties of DTTAC and DTT and the preventive effects exerted by DTTAC
      against carbon tetrachloride induced liver necrosis or cancer.

PMID- 8987120
TI  - Subacute exposure to cadmium chloride induces HSP-72 in rat liver.
AB  - Two groups of rats (n = 5) weighing 175-185 g were implanted (sc) with osmotic
      minipumps to deliver (0.5 microliter/hr) deionized water or cadmium chloride
      (CdCl2; 0.2 M) for 14 days. On completion of subacute treatment, liver and
      kidneys were collected from control and CdCl2 treated groups for analysis. We
      report that, subacute exposure to CdCl2 results in significant Cd accumulation in
      liver and kidneys, and heat-shock-protein 72 (HSP-72) induction in the liver.
      Results affirm a role for liver HSP-72 in Cd-toxicity.

PMID- 8987121
TI  - The renaissance of Hippocratic epidemiology.
AB  - Epidemiology is a small but not unimportant field in medicine. It has a clear
      identity and special spirit. It is a science that has to avoid methodologic
      dogmatism. It is a science that is strongly dependent upon collaboration with
      medical practice and basic medical science. And it is a science that in the true
      spirit of Hippocrates tries to contribute to the conquering of diseases in
      patients and in populations.

PMID- 8987122
TI  - The emergence of HIV/AIDS in Africa.
AB  - The recent spread of HIV/AIDS in Africa must be seen in the broader context of
      emerging infectious diseases, whose epidemiology results from changes in the
      equilibrium between the agent, the host, and the environment. For sexually
      transmitted agents such as HIV, epidemic spread requires a high basic
      reproductive rate (number of secondary cases generated by one primary case),
      which is itself dependent on the rate of change of sex partners, the
      transmissibility of the agent, and the duration of infectiousness. Factors
      relating to the agent which may have influenced the spread of HIV in Africa are
      viral types (HIV-1, HIV-2) and subtypes, of which at least 9 exist for the main
      group of HIV-1. Major host factors include sexual behaviour and sexual networks,
      commercial sex, sexually transmitted diseases, condom use, and circumcision
      status in males. Most difficult to study are environmental factors in the
      broadest sense, such as behavioral norms, poverty, migration, and HIV/AIDS
      prevention efforts. Any model attempting to explain HIV/AIDS emergence must
      account for the extreme heterogeneity of the epidemic within the African
      continent, and must be relevant to the application of more effective
      interventions. Although descriptive and analytic epidemiology remain necessary,
      intervention-oriented research on HIV/AIDS is now the priority in Africa.

PMID- 8987123
TI  - Overview of diabetic neuropathy.

PMID- 8987124
TI  - The clinical spectrum of diabetic neuropathy.

PMID- 8987125
TI  - The electrophysiologic profile of diabetic neuropathy.

PMID- 8987126
TI  - Metabolic alterations of peripheral nerve in diabetes.

PMID- 8987127
TI  - Peripheral nerve immunohistochemistry in diabetic neuropathy.

PMID- 8987128
TI  - Diabetic autonomic neuropathy.

PMID- 8987129
TI  - Neurotrophins and other growth factors in diabetic neuropathy.
AB  - There is enthusiasm for the application of knowledge concerning neurotrophins and
      other growth factors to human neurologic disease. New neurotrophins and other
      growth factors or inflammatory mediators that influence neurons and axons have
      been recently identified. Diabetic neuropathy may be an ideal testing ground for
      these substances because specific neurotrophins and growth factors could
      theoretically prevent loss of diabetic dorsal root ganglion (DRG) cells or
      enhance regeneration of diabetic nerves. Several of the neurotrophins support DRG
      cells in culture or prevent their loss during neonatal development, and a few
      help prevent retrograde loss of adult DRG cells after axotomy. Early Phase I
      trials suggest that nerve growth factor, brain-derived neurotrophic factor, and
      neurotrophin-3 are reasonably safe agents as administered in short-term trials to
      humans, but there are lingering experimental doubts. For example, it has not been
      established whether DRG cells are targeted by diabetes. Additional work suggests
      that simultaneous and sequential cocktails of trophins are required to support
      and rescue neurons and that the use of single agents may not be sufficient.
      Finally, it in uncertain whether trophins might act as a general tonic for DRG
      cells to prevent diabetes-related injury or whether they are actually deficient
      in human diabetic patients.

PMID- 8987130
TI  - Utility of skin biopsy in diabetic neuropathy.

PMID- 8987131
TI  - Diabetic amyotrophy: current concepts.
AB  - Diabetic amyotrophy is a disabling illness that is distinct from other forms of
      diabetic neuropathy. It is characterized by weakness followed by wasting of
      pelvifemoral muscles, either unilaterally or bilaterally, with associated pain.
      Sensory impairment is minimal in the cutaneous distribution sharing the same root
      or peripheral nerve as affected musculature. Most commonly, the onset is in
      middle age or later, although it may occur in youth. A concomitant distal
      predominantly sensory neuropathy may be present. Electrodiagnostic studies are
      most often consistent with a neurogenic lesion attributable to a lumbosacral
      radiculopathy, plexopathy, or proximal crural neuropathy. The natural course of
      the illness is variable with gradual but often incomplete improvement. The site
      of the lesion and the pathogenesis of diabetic amyotrophy remain controversial.
      Recent studies suggest a role for immunomodulating agents in certain types of
      diabetic neuropathy, including diabetic amyotrophy.

PMID- 8987132
TI  - Diabetic retinopathy and diabetic papillopathy.

PMID- 8987133
TI  - Design of controlled clinical trials for diabetic polyneuropathy.
AB  - Diabetic neuropathy is a common and debilitating complication of diabetes
      mellitus associated with high health costs. In recent years several clinical
      trials have been undertaken to test the efficacy of drug intervention in this
      disorder. The results of these trials have in general been disappointing. In this
      review we discuss selection criteria, efficacy endpoints, duration of clinical
      trials, and data collection and analyses. We offer suggestions based on past
      experiences that might improve trial design and execution in order to achieve
      improved results from treatment of this silent but common disorder.

PMID- 8987134
TI  - N of 1.

PMID- 8987135
TI  - The distribution of estrogen receptor-beta mRNA in the rat hypothalamus.
AB  - The recent cloning of a second form of the estrogen receptor (ER-beta) has made
      it possible to map the distribution of ER-beta mRNA-containing perikarya in the
      rat hypothalamus. The present in situ hybridization histochemical studies have
      detected ER-beta mRNA in the medial preoptic area; the anterior periventricular,
      paraventricular, supraoptic, arcuate, medial tuberal and medial mammillary
      nuclei; the bed nucleus of the stria terminals, and zona incerta. As previously
      described for the classical ER (ER-alpha) mRNA, a dense accumulation of ER-beta
      mRNA-expressing perikarya is present in the medial preoptic area and bed nucleus
      of the stria terminalis. In contrast, ER-beta mRNA was also concentrated in the
      paraventricular and supraoptic nuclei, brain regions which contain little or no
      ER-alpha mRNA. Moreover, the arcuate and ventromedial nuclei, areas with abundant
      ER-alpha. contain only a weak level of ER-beta hybridization signal. The
      description of ER-beta mRNA-containing perikarya in the rat hypothalamus provides
      a foundation for further morphological and physiological studies aimed at
      elucidating the role of ER-beta in the hypothalamus.

PMID- 8987136
TI  - Production and characterization of monoclonal antibodies to
      dehydroepiandrosterone sulfate: application to direct enzyme-linked immunosorbent
      assays of dehydroepiandrosterone sulfate and androsterone/epiandrosterone
      sulfates in plasma.
AB  - Mice were immunized with 5-androstene-3 beta-ol-7,17-dione-7-CMO:bovine serum
      albumin (DHEA-7-O-CMO-BSA) or 5-androstene-3 beta-ol-17-one hemisuccinate-bovine
      serum albumin (DHEA-3HS-BSA) conjugates and monoclonal antibodies were produced,
      characterized, and selected for maximum DHEAS binding. Of these hybridomas, four
      clones from DHEA-3HS-BSA-immunized mice had acceptable criteria for the
      development of a competitive enzyme-linked immunosorbent assay (ELISA) for DHEAS
      in plasma. One hybridoma supernatant from DHEA-7-O-CMO-BSA-immunized mice showed
      360% cross-reactivity to both androsterone sulfate and epiandrosterone sulfate.
      This allows the possibility of the direct determination of androsterone sulfate
      and epiandrosterone sulfate in plasma after correction for the DHEAS
      contribution. Both ELISAs employ a DHEA-3HS-thyroglobulin conjugate adsorbed to
      the wells of a standard 96-well microtiter plate. DHEAS in the standards or
      diluted plasma sample competes with immobilized DHEA-3HS-thyroglobulin for
      antibody-binding sites. Antibody is detected with anti-mouse-lg peroxidase by
      further washing, adding o-phenylenediamine substrate, and reading the absorbance
      at 492 nm. The ELISAs are simple, reproducible, and reliable and, to our
      knowledge, they are the first tests employing monoclonal antibodies to DHEAS.

PMID- 8987137
TI  - Steroidal geminal dihydroperoxides and 1,2,4,5-tetraoxanes: structure
      determination and their antimalarial activity.
AB  - Cholestane-derived gem-dihydroperoxides and tetraoxanes were synthesized starting
      from 5 alpha- and 5 beta-cholestan-3-ones by acid-catalyzed addition of hydrogen
      peroxide to the ketone. They were characterized by IR, NMR, and mass spectroscopy
      analysis aided by molecular mechanics calculations, and, in the instance of 5
      beta-cholestane-3 alpha,3 beta-dihydroperoxide (6), by x-ray analysis. The
      synthesized compounds were tested in vitro against Plasmodium falciparum Sierra
      Leone (D6) and Indochina (W2) malaria clones. All compounds were inactive to both
      clones, with the exception of tetraoxane 7a, which exhibited modest activity
      toward D6 clone with IC50 = 155 nM.

PMID- 8987138
TI  - Steroids 54. Amino acylamidosteroids.
AB  - Aminosteroids were prepared and acylated with protected amino acids by means of
      the mixed anhydride or the active ester method. The tert-butyloxycarbonyl- (BOC)
      protecting group was eliminated by acidolysis, and the benzyloxycarbonyl- (Z)
      group by catalytic hydrogenation. 3 beta- and 6 beta-Glycylamidosteroids were
      prepared by indirect amination of chloroacetamido derivatives, formed by the
      Ritter reaction on the corresponding 3 alpha,5 alpha-cyclo and 5 alpha,6 alpha
      epoxy steroids. Water-soluble double salts were produced from the compounds for
      pharmacological investigations.

PMID- 8987139
TI  - Nucleosteroids: reaction of activated purine bases with steroidal reactive
      centers.
AB  - The reaction of 16 alpha,17 alpha-epoxy-3 beta-hydroxy-5-pregnen-20-one with 6
      methyl thiopurine activated with sodium hydride leads to the coupling of the
      purine base with the carbonyl group at C-20 to give a steroidal nucleoside
      analog, which is termed "nucleosteroid." In the presence of an excess of purine,
      a parallel reaction occurs in which the oxirane ring is opened, presumably by
      nucleophilic attack of an intermediate C-20 oxyanion, and yields as the main
      product of reaction an oligomeric mixture of nucleosteroid units linked together
      by ether linkages. Analogous reactions conducted with 3 beta-hydroxy-5-pregnen-20
      one and with 3 beta,17 alpha-dihydroxy-5-pregnen-20-one gave minor amounts or
      only traces of the corresponding coupling adduct, and oligomerization did not
      occur. This behavior is interpreted in terms of the conformational differences
      showed by the different steroids to the attack by the purine.

PMID- 8987140
TI  - Synthesis of estrogen sulfamates: compounds with a novel endocrinological
      profile.
AB  - Estrogen sulfamates are promising hormones by oral administration. Therefore,
      generally applicable and convenient methods for the multigram synthesis of these
      derivatives are desirable. Numerous estra-1,3,5(10)-trienes derived from estrone,
      estradiol. 14 alpha,15 alpha-methylenestradiol, ethinylestradiol, and estriol
      have been esterified with sulfamoyl chloride and N-methylsulfamoyl chloride by a
      novel approach involving the use of 2,6-di-tert-butylpyridines as bases and
      chemoselective hydroxy group protections. These pathways circumvent the
      nonselective formation of esters and side reactions by in situ generated
      azasulfenes. For toxicological and clinical studies a new synthesis of estrone
      sulfamate on a 100-g scale was developed using dimethylformamide as the solvent
      and base.

PMID- 8987141
TI  - Stereochemical probes for the estrogen receptor: synthesis and receptor binding
      of (17 alpha,20E/Z)-21-phenyl-19-norpregna-1,3,5(10), 20-tetraene-3,17 beta
      diols.
AB  - Previous studies from our laboratory using 17 alpha-E- and 17 alpha-Z-halovinyl
      and phenylthiovinyl estradiols demonstrated a marked preference for the Z
      stereochemistry and a significant steric tolerance for the Z-vinyl substituent.
      To further explore the extent of that stereochemical preference and steric
      tolerance we have prepared stereoselectively the 17 alpha-E- and 17 alpha-Z
      phenylvinyl estradiols (E- and Z-styrylestradiols). The results, in addition to
      demonstrating a facile preparation of the target compounds, supported the
      previously observed stereochemical and steric effects. The relative binding
      affinities for the Z isomer were 3-4 fold greater than the E isomer at both 4
      degrees C and 25 degrees C, and only one-half to one-fourth those of estradiol
      under similar conditions. The developing model for ligand-accessible space within
      the estrogen receptor suggests that Z-phenylvinyl estradiols may provide
      interesting and useful probes for mapping the receptor.

PMID- 8987142
TI  - Microdialysis and SPECT measurements of amphetamine-induced dopamine release in
      nonhuman primates.
AB  - The competition between endogenous transmitters and radiolabeled ligands for in
      vivo binding to neuroreceptors might provide a method to measure endogenous
      transmitter release in the living human brain with noninvasive techniques such as
      positron emission tomography (PET) or single photon emission computerized
      tomography (SPECT). In this study, we validated the measure of amphetamine
      induced dopamine release with SPECT in nonhuman primates. Microdialysis
      experiments were conducted to establish the dose-response curve of amphetamine
      induced dopamine release and to document how pretreatment with the dopamine
      depleter alpha-methyl-para-tyrosine (alpha MPT) affects this response. SPECT
      experiments were performed with two iodinated benzamides, [123I]IBZM and
      [123I]IBF, under sustained equilibrium condition. Both radio-tracers are specific
      D2 antagonists, but the affinity of [123I]IBZM (KD-0.4 nM) is lower than that of
      [123I]IBF (KD 0.1 nM). With both tracers, we observed a prolonged reduction in
      binding to D2 receptors following amphetamine injection. [123I]IBZM binding to D2
      receptors was more affected than [123I]IBF by high doses of amphetamine,
      indicating that a lower affinity increases the vulnerability of a tracer to
      endogenous competition. With [123I]IBZM, we observed an excellent correlation
      between reduction of D2 receptor binding measured with SPECT and peak dopamine
      release measured with microdialysis after various doses of amphetamine.
      Pretreatment with alpha MPT significantly reduced the effect of amphetamine on
      [123I]IBZM binding to D2 receptors, confirming that this effect was mediated by
      intrasynaptic dopamine release. Together, these results validate the use of this
      SPECT paradigm as a noninvasive measurement of intrasynaptic dopamine release in
      the living brain.

PMID- 8987143
TI  - GABA induces GABAergic MSCs in cultured embryonic rat thalamic neurons.
AB  - Application of 0.1-10 microM GABA in the vicinity of cultured embryonic rat
      thalamic neurons recorded with patch pipettes in the presence of 2 microM TTX
      induced or increased the frequency of miniature synaptic currents (MSCs) that
      reversed polarity at the Cl- equilibrium potential. These MSCs were blocked by
      the GABAA receptor antagonist bicuculline and exhibited exponential decay
      kinetics that closely paralleled those estimated from fluctuation analysis of Cl-
      channels activated pharmacologically by applying 1-10 microM GABA to the same
      cells. We conclude that the MSCs are mediated by GABA. Application of the GABAA
      receptor agonist muscimol activated Cl- current but failed to induce GABAergic
      MSCs while submicromolar concentrations of GABA evoked GABAergic MSCs but did not
      activate Cl- channels. The GABAB receptor agonist (-)baclofen did not mimic GABA
      in inducing MSCs. Induction of GABAergic MSCs by GABA required extracellular
      Ca2+. Verapamil and Co2+, which block voltage-dependent calcium channels,
      completely blocked GABA-induced MSCs independent of their effects on the direct
      activation of a Cl- current response. The results indicate that GABA can trigger
      GABAergic Cl(-)-dependent MSCs in a Cao(2+)-dependent manner. The mechanism may
      involve a novel receptor and/or signal transduction pathway.

PMID- 8987144
TI  - Electron microscopic study of GABAergic synaptic innervation of nitric oxide
      synthase immunoreactive neurons in the dorsal raphe nucleus in the rat.
AB  - A double immunocytochemical method combining the preembedding avidin biotin
      peroxidase complex technique and the postembedding immunogold technique was used
      to examine synaptic interactions between GABAergic and nitric oxide synthase
      containing neurons in the same tissue sections of the dorsal raphe nucleus of the
      Wistar white rat. Although a large number of immunogold stained GABAergic axon
      terminals were found to be presynaptic to dendrites containing nitric oxide
      synthase-like immunoreaction product, synapses between GABA-like immunoreactive
      axon terminals and nitric oxide synthase-like immunoreactive perikarya were rare.
      The labeled boutons were found to make symmetrical and asymmetrical synapses. No
      axo-axonic synapse was found. These results suggest that GABAergic neurons could
      modulate nitric oxide producing neurons in the dorsal raphe nucleus through
      direct synaptic relations.

PMID- 8987145
TI  - Localization of monoamine oxidase A and B mRNA in the rat brain by in situ
      hybridization.
AB  - Monoamine oxidases A and B (MAOA and MAOB) are the major catabolic isoenzymes of
      catecholamines and serotonin in the mammalian brain. Although the distribution of
      the monoamine oxidase protein has been mapped by ligand binding and
      immunohistochemistry, the sites of MAOA and MAOB synthesis have not been
      precisely determined. In this study, we used in situ hybridization to visualize
      MAOA and MAOB mRNA in the rat brain by using specific cDNA and oligonucleotide
      probes. MAOA mRNA was localized in major monoaminergic cell groups, such as the
      dorsal vagal complex, the C1/A1 groups, the locus ceruleus, the raphe nuclei, the
      substantia nigra, and the ventral tegmental area. MAOA mRNA was also found in
      forebrain structures, such as the cortex, the hippocampus, the thalamus, and the
      hypothalamus. In contrast to the distribution of MAOA mRNA, high levels of MAOB
      mRNA were present in only three brain regions: the area postrema, the subfornical
      organ, and the dorsal raphe. The in situ visualization of MAO mRNA demonstrates
      that MAOA mRNA synthesis is wide spread in many catecholaminergic and
      serotonergic cell groups, whereas MAOB mRNA synthesis is far more discrete and
      limited. The different expression patterns of MAOA and MAOB suggests that may
      also have different physiological functions.

PMID- 8987146
TI  - Dopamine efflux in the rat nucleus accumbens evoked by dopamine receptor
      stimulation in the entorhinal cortex is modulated by oestradiol and progesterone.
AB  - This study compared the effects of dopamine receptor stimulation in the
      entorhinal cortex on dopamine release in the nucleus accumbens, measured by in
      vivo microdialysis in conscious Sprague-Dawley rats, with and without oestradiol
      and progesterone priming. Nonselective dopamine receptor stimulation with
      apomorphine reduced dopamine release in the nucleus accumbens, an effect which
      was prevented by injection of cis-flupenthixol into the entorhinal cortex.
      Selective D1 receptor stimulation with SKF38393 increased dopamine release,
      whereas selective D2 receptor stimulation with quinpirole did not affect dopamine
      release. Combined administration of oestradiol and progesterone potentiated the
      response to apomorphine and prevented the response to SKF38393. The effects of
      single hormone administration on the response to apomorphine suggested that the
      modulation was primarily due to oestradiol enhancing effects of progesterone.
      Experiments with high [K+] suggested these hormonal effects were exerted
      predominantly in the entorhinal cortex. The present experiments have demonstrated
      that dopaminergic modulation of transmission in a cortico-striatal loop linking
      temporal and prefrontal cortex is regulated by oestradiol and progesterone.
      Dysfunction in this system in humans may give rise to affective and cognitive
      symptoms which may, if initiated by a postpartum fall in oestrogen and
      progesterone concentrations, constitute the core pathophysiology of puerperal
      psychosis.

PMID- 8987147
TI  - Noradrenergic neurons release both noradrenaline and neuropeptide Y from a single
      pool: the large dense cored vesicles.
AB  - In peripheral adrenergic nerve endings, noradrenaline is stored in two different
      types of vesicles, the large and the small dense cored vesicles. A systematic
      study was undertaken to examine the release of noradrenaline and neuropeptide Y
      from dog spleen and rat vas deferens under various conditions of stimulation,
      particularly those which previously have demonstrated a differential regulation
      of exocytosis of the different types of storage vesicles. Here we present
      evidence that noradrenaline is released by exocytosis exclusively from the large
      dense cored vesicles, in which it is stored together with neuropeptide Y. Upon a
      single stimulation (at frequencies varying from 2-20 Hz), the release of
      noradrenaline and neuropeptide Y from the dog splenic nerve increased with the
      frequency of stimulation, but the ratio of noradrenaline to neuropeptide Y
      remained constant. After repeated stimulation of the splenic nerve, both
      substances' overflow decreased gradually and in parallel to values of 12.5% and
      11.1% of the first stimulation for noradrenaline and neuropeptide Y,
      respectively. Similarly, repeated stimulation of the rat vas deferens (of which
      only 2-10% is large dense cored vesicles, whereas in the dog splenic nerve the
      large dense cored vesicles make up 30-40% of the total vesicle population) with
      120 mM K+, in the presence of phentolamine, caused a gradual and parallel decline
      in the release of noradrenaline and neuropeptide Y (31.6% and 34.0%,
      respectively). Moreover, omega-conotoxin (10(-8) M to 10(-5) M) had a similar
      inhibitory effect on the release of both substances, alpha-latrotoxin (10(-9) M)
      evoked a parallel release of both noradrenaline and neuropeptide Y. The results
      indicate that noradrenaline in peripheral noradrenergic nerves is released
      exclusively from large dense cored vesicles by an exocytotic mechanism.

PMID- 8987148
TI  - L-DOPA modulates striatal dopaminergic function in vivo: evidence from PET
      investigations in nonhuman primates.
AB  - Significant increases in striatal L-[11C]DOPA retention were observed in adult
      female rhesus monkeys with positron emission tomography (PET) following
      administration of drugs that increase cerebral L-DOPA concentrations. The monkeys
      were scanned twice: at baseline (using 10-50 micrograms of tracer substance) and
      during continuous administration of L-DOPA (3 or 15 mg/kg/h) and 6-R-Erythro
      4,5,6,7-tetrahydrobiopterin (6R-BH4) (5 mg/kg/h) and during combined
      administration of both drugs. PET scans of L-[11C]DOPA distribution were obtained
      in GE2048-15B or GE4096-15WB Plus positron tomographs. In all studies the
      specific striatal L-[11C]DOPA influx rate increased by an average of 17-20%.
      These increases were significantly higher than the retest variability obtained
      with saline infusions under identical experimental conditions. In individual
      monkeys the magnitude of increase in the striatal L-[11C]DOPA influx rate varied
      from no effect of the drug infusion to a 45% increase. Taken together, the
      results of this study demonstrate that L-DOPA in itself can affect dopaminergic
      neurotransmission in vivo and also adds further evidence that the neuromodulatory
      effects of the amino acid are predominantly autoreceptor antagonist-like. The
      findings most likely have importance for the further understanding of the
      dopaminergic system in neurodegenerative and psychiatric disorders.

PMID- 8987149
TI  - Presynaptic and postsynaptic GABAB receptors of neocortical neurons of the rat in
      vitro: differences in pharmacology and ionic mechanisms.
AB  - The properties of pre- and postsynaptic GABAB receptors were investigated with
      intracellular recordings from rat neocortical neurons in vitro. An antagonist of
      the GABAB receptor (CGP 35348) and ions or drugs interfering with GABAB receptor
      mediated K+ conductance (Ba2+, QX 314) were employed to delineate possible
      differences. CGP 35348 reduced the conductance of the late inhibitory
      postsynaptic potential (IPSPB) in a dose-dependent manner. Neither the early
      GABAA receptor-mediated inhibitory postsynaptic potential (IPSPA), nor resting
      membrane potential or direct excitability, were consistently affected by CGP
      35348. Bath application of 100 mumol/l Ba2+ decreased IPSPB conductance to about
      40% and increased IPSPA conductance to 130% of control. The depression of a
      second IPSP by a pair of stimuli (paired pulse depression, or PPD) was used as an
      index for presynaptic GABAB receptor activation. Neither CGP 35348 nor Ba2+
      exerted significant effects on the PPD at intervals of 400 msec. The dependence
      of PPD on the latency of the interval of the stimulus pair was investigated after
      intracellular applicatio of QX 314 had virtually abolished the IPSPB. Decreasing
      the stimulus interval from 500 msec to 100 msec revealed a stronger depression of
      the second IPSPA. Application of CGP 35348 alleviated PPD for stimulus intervals
      below 300 msec. The data indicate a distinct pharmacological difference between
      pre- and postsynaptic GABAB receptors. Moreover, we suggest that two temporally
      distinct presynaptic GABAB receptor effects contribute to PPD: a short-lasting
      effect, sensitive to CGP 35348, and a long-lasting effect, insensitive to CGP
      35348. The latter is insensitive to Ba2+, implying that this component is not
      associated with a K+ conductance mechanism.

PMID- 8987150
TI  - Localized changes in GABA receptor-gated chloride channel in rat brain after long
      term haloperidol: relation to vacuous chewing movements.
AB  - Several lines of evidence suggest that the GABAergic system may be involved in
      dyskinetic side effects of long-term neuroleptic treatment. In this study,
      [35S]TBPS autoradiography was used to investigate changes in the GABA receptor
      gated chloride ionophore in rats showing vacuous chewing movements (VCMs) after
      21 weeks of treatment with haloperidol decanoate (HAL). A significant decrease in
      [35S]TBPS binding was observed in the globus pallidus of HAL-treated rats,
      compared to vehicle-treated controls (+23%, P < 0.001). However, this was equally
      observed in rats showing high VCM levels (> 70 counts/5 min) and those showing
      low VCM levels (< 30 counts/5 min), suggesting that this pallidal change cannot
      account for the differential development of VCMs after long-term HAL. In
      contrast, a small but significant increase in [35S]TBPS binding in the
      ventrolateral caudate-putamen was seen in animals in the high VCM group (+16%, P
      < 0.03), but not in those in the low VCM group, when compared to vehicle-treated
      controls. No significant alterations were found in other basal ganglia regions
      and related structures, including the substantia nigra, subthalamic nucleus,
      entopeduncular nucleus, and thalamic nuclei. The results are consistent with the
      notion of altered striatopallidal output as a result of chronic HAL treatment.
      They also suggest the possibility that alterations in GABA receptor-linked Cl
      channels in the ventrolateral caudate-putamen may contribute to the development
      of dyskinetic syndromes after long-term neuroleptic treatment.

PMID- 8987152
TI  - Real-time measurement of stimulated 5-hydroxytryptamine release in rat substantia
      nigra pars reticulata brain slices.
AB  - Fast cyclic voltammetry at a carbon fibre microelectrode was used to measure 5-HT
      signals following electrical or chemical stimulation in rat substantia nigra pars
      reticulata slices. Chemical stimulation with (+)-amphetamine or veratrine gave
      signals which were indistinguishable from those of exogenous 5-HT. Electrical
      stimulation of sufficient duration gave voltammetric signals which were
      characteristic of 5-HT. Release of dopamine was not detected following either
      chemical or electrical stimulation. The 5-HT signals were attenuated by TTX and
      enhanced by fluvoxamine. It was not possible to demonstrate regulation of 5-HT
      release in the SNr by 5-HT1B autoreceptors using CGS 12066A or methiothepin.
      Signal following electrical stimulation were not enhanced by either benztropine
      or GBR12909, or modified in the presence of either quinpirole or sulpiride. We
      conclude that 5-HT release can be detected voltammetrically in the SNr; 5-HT
      release is likely to be from axon terminals, but somatodendritic DA release could
      not be detected.

PMID- 8987151
TI  - Differential distribution of tyrosine hydroxylase fibers on small and large
      neurons in layer II of anterior cingulate cortex of schizophrenic brain.
AB  - A series of recent postmortem investigations of the anterior cingulate cortex in
      schizophrenic brain have suggested that there may be a loss and/or impairment of
      inhibitory interneurons in layer II. It has been postulated that changes of this
      type could secondarily result in a relative increase of dopaminergic inputs to
      GABAergic interneurons. To test this hypothesis, an immunoperoxidase technique
      was developed to extensively and reliably visualize tyrosine hydroxylase
      immunoreactive (TH-IR) varicose fibers in human postmortem cortex. This method
      has been applied to the anterior cingulate (ACCx; Brodmann area 24) and
      prefrontal (PFCx: Brodmann area 10) cortices from a cohort of 15 normal control
      and 10 schizophrenic cases. The number of TH-IR varicosities in contact with
      large neurons (LN), small neurons (SN), and neuropil (NPL) was blindly analyzed
      using a computer-assisted microscopic technique. There was no significant
      difference in density of TH-IR varicosities in apposition with either LN or SN
      cell bodies observed in either ACCx or PFCx of schizophrenics when compared to
      normal controls. The density of varicosities was significantly reduced in NPL of
      layers V and VI in ACCx, but 2 neuroleptic-free cases did not show this change,
      suggesting that these decreases of TH-IR varicosities may be related to
      antipsychotic effects on corticostriatal projection cells in this region. When
      the density of TH-IR varicosities on SNs was compared to that observed on LNs,
      both groups showed a higher density on SNs. In ACCx, this pattern was much more
      pronounced for the schizophrenic group, particularly in layer II where the
      density on SNs was three times higher than that for LNs (P = 0.01). Unlike the
      changes in layer V, this latter change in layer II showed no relationship to
      neuroleptic exposure. There was a positive correlation between age and the
      density of TH-IR varicosities on SNs of layer II in ACCx; however, the patients
      were younger than the controls and would have been expected to show a lower
      density, rather than a higher one, if age considerations had accounted for the
      group differences. Overall, the results reported here suggest that there are no
      gross differences in the distribution of TH-IR varicosities in various laminae of
      the dorsolateral prefrontal cortex. In the anterior cingulate region, however,
      there may be a significant shift in the distribution of TH-IR varicosities from
      large neurons to small neurons that occurs selectively in layer II of
      schizophrenic subjects. Using size criteria, the majority of small neurons are
      likely nonpyramidal, while the majority of large neurons are predominantly
      pyramidal in nature. Taken together with other accumulating evidence of
      preferential abnormalities in this lamina of the cingulate region, the findings
      reported here are consistent with a model of schizophrenia in which a subtle
      "miswiring" of ventral tegmental inputs may result in a relative, though not
      absolute, hyperdopaminergic state with respect to an impaired population of
      GABAergic interneurons.

PMID- 8987153
TI  - Long-lasting decreases of AMPA responses following postsynaptic activity in
      single hippocampal neurons.
AB  - Direct postsynaptic depolarization and firing of single CA1 neurons caused
      decreased responses to iontophoresed alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA). Since there was no associated change in the excitatory
      postsynaptic potential (EPSP) evoked by electrical stimulation in the same band
      of stratum radiatum, we infer that the decreased AMPA response was mediated
      predominantly by extrasynaptic receptors. The decreased AMPA response developed
      within 10-30 min after conditioning, a time course similar to the delayed
      increase in AMPA responses associated with long-term potentiation (LTP) [Davies
      et al. (1989), Nature, 338:500-503; Sergueeva et al. (1993), Neuropharmacology,
      32:933-935]. Our observations suggest the existence of mirror-image processes
      that may regulate AMPA receptors and possibly synaptic efficacy.

PMID- 8987154
TI  - Inhibition of 7-dehydrocholesterol reductase by the teratogen AY9944: a rat model
      for Smith-Lemli-Opitz syndrome.
AB  - Our aim is to verify the validity of a rat model proposed for Smith-Lemli-Opitz
      (SLO) syndrome, a developmental disorder characterized by a defect in 7
      dehydrocholesterol-delta 7 (7DHC)-reductase and by facial dysmorphism close to
      the holoprosencephaly caused by the teratogen AY9944. We investigated the sterol
      profile in rats treated with AY9944 blocking 7DHC-reductase. AY9944 was given
      orally to rats on gestation day 3 (D3). The sera were sampled for kinetic data on
      D3, D6, D9, D12, and D21. Cholesterol was measured in parallel by the routine
      enzymatic method and by the gas chromatography/mass spectrometry (GC-MS)
      procedure used in SLO diagnosis. In addition to sterols, we dosed steroid
      hormones punctually on D4 and on D10, and examined D21 fetuses in other animals.
      The enzymatic method was not specific for cholesterol, and measured 70% pure 7DHC
      added to a normal serum. On D21, 77% live fetuses showed pituitary agenesis.
      Cholesterol was rapidly reduced by more than 50% on D6 involving an accumulation
      of 7DHC, 8DHC, and trienols, as identified in SLO-affected children. The most
      abundant 7DHC reached a maximum from D9 to D12, equaling cholesterol on D9 (11
      mg/dl). On D10, the magnitudes of hypocholesterolemic and of 7DHC accumulation
      were found to be dose-dependent. Progesterone was reduced as early as 24 hr after
      treatment and dropped to 40% of the levels in the controls on D10, correlating to
      the decrease in cholesterolemia. This rat model reproduces the same biochemical
      perturbations as seen in SLO, strongly suggesting that aberrant sterols (7DHC,
      8DHC, or nortrienol) may contribute to the developmental defects.

PMID- 8987155
TI  - Mesonephros has a role in limb development and is related to thalidomide
      embryopathy.
AB  - Recent studies have demonstrated a link between limb reduction defects and
      mesonephros removal [Geduspan and Solursh, 1992) Dev. Biol., 151:242-250].
      However, there is some question as to whether the limb-reduction defects seen in
      that study resulted from the removal of mesonephros or from the formation of scar
      tissue medial to the limb territory. The current study was conducted to test the
      hypothesis that elimination of the mesonephros without producing scar tissue
      adjacent to the limb will adversely affect limb morphogenesis. The hypothesis was
      tested by the insertion of tantalum foil barriers into various levels of the
      intermediate mesoderm of developing chick embryos to prevent the caudal
      elongation of the mesonephros. Limb reduction defects were obtained when the
      mesonephros was prevented from forming caudal to somite 14. No limb defects were
      seen when a foil barrier was placed into the intermediate mesoderm at the level
      of somite 21 or 25. Our results support the notion that a signal from the
      mesonephros is necessary for normal limb development. In addition, it appears
      that a craniocaudal factor emanating from the mesonephros plays a role in limb
      development. The limb reduction defects obtained in this study were also compared
      to the pattern of thalidomide embryopathy in humans. There is a close
      correspondence between the types of limb reduction anomalies seen with
      thalidomide and mesonephric blocks and between the severity of defects vs. the
      timing of thalidomide intake or mesonephric blockage. A model for possible
      thalidomide embryopathy is presented.

PMID- 8987156
TI  - Cervical flexion: its contribution to normal and abnormal cardiac morphogenesis.
AB  - Although His in 1881 and Patten in 1922 suggested that cervical flexion could
      play an important role in normal cardiac morphogenesis, until recently this
      hypothesis has been largely neglected. The purpose of this report is to present
      data indicating that prevention of cervical flexion leads to double outlet right
      ventricle (DORV), which is unrelated to any affect on neural crest cell
      migration. At stage 11-12, suture material was inserted into the neural tube to
      prevent cervical flexion. Six out of 22 experimental embryos survived until stage
      38 and 5 out of 6 had DORV. Neither abnormalities of the aortico-pulmonary septum
      nor interruption of the aortic arch were observed at dissection. Hemodynamic
      studies performed at stage 18 revealed distinctive characteristics that are
      inconsistent with hemodynamic studies previously reported following neural crest
      ablation. With respect to immunohistochemical studies using neural crest
      associated antigen HNK-1 antibody, normal migration of neural crest cells was
      noted in the outflow tract in the experimental embryos at stage 22. These
      hemodynamic and immunohistochemical studies suggest that insertion of suture
      material into the neural tube at stage 11-12 does not jeopardize neural crest
      migration. We propose that reduction in cervical flexion increases the distance
      between the future aorta and the left ventricle, which prevents the transition of
      intracardiac flow pattern from a serial circulation to a parallel one, leaving
      persistence of a "double outlet" from the right ventricle.

PMID- 8987157
TI  - Is there a cocaine syndrome? Dysmorphic and anthropometric assessment of infants
      exposed to cocaine.
AB  - It was suggested that a "fetal cocaine syndrome" exists. The objective of this
      study was to systematically investigate whether or not a "cocaine syndrome"
      exists. The setting was Parkland Memorial Hospital, a large urban public hospital
      in Dallas, TX, where approximately 15,000 infants are delivered annually. Infants
      who tested positive by urinalysis for cocaine (n = 25) were included in this
      study. Controls negative for cocaine (n = 25) were matched to cocaine-exposed
      infants for estimated gestational age, sex, and race. A standardized
      dysmorphology examination (135 features) and a series of anthropometric measures
      (n = 22) were done for each cocaine-exposed and control infant by an observer
      blinded to drug-exposure status. Fetal growth retardation characterized cocaine
      exposed infants. No characteristic pattern of minor dysmorphic or anthropometric
      features of the face, limbs, or torso was observed among cocaine-exposed infants.
      Cocaine-exposed infants lack a facial gestalt or torso/limb features that would
      characterize a syndrome. If a "cocaine syndrome" that can be characterized
      dysmorphologically and/or anthropometrically exists, its occurrence seems
      infrequent.

PMID- 8987158
TI  - All-trans-retinoyl-beta-glucuronide is a potent teratogen in the mouse because of
      extensive metabolism to all-trans-retinoic acid.
AB  - All-trans-retinoyl-beta-D-glucuronide (all-trans-RAG) is a water-soluble
      derivative of all-trans-retinoic acid (all-trans-RA) and has been characterized
      as an endogenous metabolite of vitamin A in rat bile and kidney. All-trans-RAG
      was previously demonstrated to be a major metabolite after application of all
      trans-RA in several species (mouse, rat, rabbit, monkey); all-trans-RAG was
      described in these experiments to exhibit a very low placental transfer to the
      embryo. Because retinoid-like activity has been found after application of all
      trans-RAG in vivo as well as in several in vitro systems, and because of its low
      placental transfer, this glycoconjugate appeared to be an interesting retinoid
      with possible therapeutic activity, but reduced teratogenicity. Here we
      investigated the teratogenic activity of all-trans-RAG in comparison to all-trans
      RA in mice, and performed accompanying pharmacokinetic studies. Surprisingly, all
      trans-RAG was more teratogenic than equimolar doses of all-trans-RA following
      subcutaneous application on day 11 of gestation in the mouse (20 mumol/kg body
      weight). Pharmacokinetic studies revealed that all-trans-RAG was extensively
      hydrolyzed to all-trans-RA and that the plasma area under the concentration-time
      curve (AUC) of all-trans-RA following all-trans-RAG application exceeded the
      plasma AUC value of all-trans-RA following application of all-trans-RA. Extensive
      hydrolysis of all-trans-RAG was also observed after intravenous application of
      this glycoconjugate. Transfer of all-trans-RAG to the embryo was low, but
      transfer was high to maternal organs such as the liver and kidney. These in vivo
      studies suggest that all-trans-RAG serves as a precursor of all-trans-RA by the
      intravenous and subcutaneous routes, and application of all-trans-RAG results in
      high and teratogenic in vivo exposure to all-trans-RA.

PMID- 8987159
TI  - Developmental toxicity of ibutilide fumarate in rats after oral administration.
AB  - In two Segment II Teratology studies, timed-pregnant Crl:CD[BR] (Sprague-Dawley)
      rats were treated orally (gastric intubation) on days 6-15 of gestation with
      ibutilide fumarate (ibutilide), a class III antiarrhythmic that has been shown to
      increase the refractory period and action potential duration of myocardial cells.
      In the first study, ibutilide does of 20, 40, and 80 mg/kg/ day were tested.
      Although maternal toxicity was equivocal in the 80 mg/kg/day group, all 23 rats
      that conceived had entirely resorbed liters when the animals were killed on day
      20 of gestation. Similarly, 12 of 24 litters were completely resorbed in the 40
      mg/kg/day group, with an 87.7% postimplantational loss. Of the surviving fetuses
      in this group, 48.6% had at least one malformation. The incidences of malformed
      pharynx and malformed palate, along with adactyly, were statistically
      significantly higher in this group than in the control group. In addition, a
      significant (P < 0.05) increase in total malformations (5.7% of the fetuses),
      relative to the controls (0.8%), was found for the 20 mg/kg/day group. Since a no
      observed adverse effect level (NOAEL) was not found, a second teratology study
      was performed. In this study, the ibutilide doses were 5, 10, and 20 mg/kg/day.
      The 20 mg/kg/day dose was again teratogenic with 9.2% of the fetuses malformed,
      as compared to a control value of 1.0%. Also, the incidences of scoliosis and
      interventricular septal defect were statistically significantly higher in this
      group. Although statistically significant differences were not detected,
      scoliosis was also found in the 10 mg/kg/day group (3 fetuses in 2 litters),
      along with a significant dose-response trend for this malformation. As the
      result, the NOAEL for ibutilide teratogenicity in rats was set at 5 mg/kg/day.
      This dose is 4 times the proposed maximum clinical dose (two 1 mg doses, each
      infused over 10 minutes, or 0.033 mg/kg for a 60 kg person), when corrected for
      2.6% oral bioavailability in the rat at a dose of 10 mg/kg, as determined in
      separate studies.

PMID- 8987160
TI  - The treatment of deep vein thrombosis with continuous intravenous low-molecular
      weight dermatan sulphate (Desmin). A pilot study.
AB  - Eight patients with femoro-popliteal or sural DVT, confirmed by phlebography,
      were treated with intravenous Desmin (LMW-dermatan sulphate): on the first day,
      after an initial i.v. injection of 400 mg, all patients received an infusion of
      800 mg in 500 ml of saline, during 24 hours; this infusion was repeated in each
      of the subsequent 9 days (global treatment period: 10 days). To monitor efficacy
      of the antithrombotic treatment a phlebography, with calculation of Marder score,
      was repeated at the end of treatment. Laboratory tests monitoring blood
      coagulation were carried out: aPTT, TT, PT. Factor Xa inhibition (by chronometric
      and chromogenic method), Stachrom DS, fibrinogen, prothrombin fragments F1 + 2
      and TAT. Seven patients completed the ten-day treatment: 6 patients evidenced
      good improvement of the phlebographic patterns, 1 remained stationary and 1
      patient was withdrawn due to adverse events. During the ten days treatment we did
      not observe any variation of blood coagulation tests. Desmin tolerability was
      good and no haemorrhagic episodes were registered. The collected results point to
      a good antithrombotic activity of the new LMW-dermatan sulphate, that deserves to
      be further evaluated with controlled investigations on larger number of patients.

PMID- 8987161
TI  - Involvement of phosphoprotein phosphatase 1 in collagen-platelet interaction.
AB  - The binding of type I collagen to its receptor initiates platelet aggregation,
      but the relationship of the receptor to other signal transduction components is
      not yet established. Correlation of platelet aggregation and anti-type I collagen
      receptor antibody immunoprecipitation of type I collagen treated [32PO4]-labeled
      platelets showed that there are two phosphoproteins (M(r) 53 kDa and 21 kDa) that
      coprecipitated with the 65 kDa platelet type I collagen receptor. In the present
      investigation, we have identified one of the phosphoproteins. A soluble component
      the 100,000x g supernatant fraction of 53 kDa protein is recognized by polyclonal
      anti-PP1 antibody. The activity of the precipitated phosphatase is inhibited by
      okadaic acid and inhibitor 1, suggesting that it is protein phosphatase 1 (PP 1).
      Phosphorylation decreases PP 1 activity as was found with [32PO4]-phosphorylase b
      as the substrate. The immunocoprecipitation of the type-1 collagen receptor and
      PP 1 inot the result of cross reactivity of the anti-type I collagen receptor
      antibody with the PP I protein. These results indicate that the platelet type I
      collagen receptor, PP 1, and unidentified 21 kDa protein are in close association
      with the platelet type I collagen receptor upon the binding of type I collagen by
      the receptor.

PMID- 8987162
TI  - The quantitative reduction by acute-dose warfarin of venous thrombosis in normal
      and hyperthrombotic rats.
AB  - Warfarin was tested for its relative ability to reduce thrombosis in two series
      of rats. In one series both the warfarin and control animals were made
      hyperthrombotic by an infusion of ellagic acid just before thrombosis was
      measured. In the second series (termed normothrombotic) no thrombotic stimulant
      was given. In all, 179 test and 109 control animals were used. Warfarin was given
      in varying doses to the test animals. Ellagic acid was administered as a single
      standard dose. At operation, two test animals and one control of similar weight
      were operated on concurrently. Thrombosis was measured by the weight of thrombus
      occurring on a standard 2 cm intravenous platinum wire in one hour. In optimum
      dose, warfarin reduced thrombus formation by 74% in the unstimulated series and
      by 83% in the hyperthrombotic one, when the mean factor II levels were 18% and
      19% respectively. The residual thrombus under warfarin treatment was, however,
      greater in the hyperthrombotic than in the unstimulated animals at all levels of
      factor II. Best correlation of thrombus weight was with factor II in unstimulated
      animals.

PMID- 8987163
TI  - Inhibition of thrombin by hirudin genetically fused to wild-type or mutant
      antithrombin.
AB  - Recombinant fusion proteins consisting of hirudin variant 3 (HV3) fused at its C
      terminus to either of two forms of mature rabbit antithrombin (AT) were generated
      in COS-I cells. HV3 fused to wild-type AT was designated HAT, while a similar
      chimeric protein in which the P12 residue of AT was mutated from Ala to Thr, was
      designated HAT(H) for the Hamilton (A382T) mutation. Addition of the HV3 domain
      resulted in a decreased mobility of both HAT and HAT(H) relative to COS-derived
      AT (68 kDa versus 60 kDa). Both proteins had a greatly increased ability to
      inhibit thrombin in amidolytic activity assays, relative to recombinant AT.
      Addition of heparin to these reactions was without effect. Incubation of
      conditioned media containing recombinant AT with 125I-labelled thrombin resulted
      in the formation of SDS-stable AT-IIa complexes; no such complexes were detected
      in identical reactions containing either HV3-AT fusion protein. The two proteins
      did not differ significantly in their ability to compete for the binding of 125I
      labelled thrombin to immobilized HV1 (CGP 39393). Both proteins were found to
      bind to heparin-Sepharose, but less tightly than unfused AT. This property was
      demonstrated by the peak elution of the fusion proteins at 0.65 M NaCl, as
      compared to that of COS-derived AT at 1.05 M NaCl. We conclude that the fusion
      proteins inhibit thrombin with similar affinity to unfused hirudin via their
      hirudin and not their antithrombin domains. The heparin-binding capability of
      these proteins may indicate the acquisition of vessel wall binding capacity by
      these novel forms of recombinant hirudin.

PMID- 8987164
TI  - A novel G/A and the 4G/5G polymorphism within the promoter of the plasminogen
      activator inhibitor-1 gene in patients with deep vein thrombosis.
AB  - Plasma plasminogen activator inhibitor-1 (PAI-1) level was observed to be
      associated with sequence variations at the PAI-1 locus. Therefore, PAI-1 gene
      promoter was screened for possibly new polymorphisms and to investigate the
      contribution of these sequence variations to PAI-1 levels in patients with deep
      vein thrombosis (DVT). DNA was isolated from blood of 83 consecutive unrelated
      patients (42 +/- 11 years old) and from 50 apparently healthy subjects of similar
      age and gender distribution. Six fragments covering DNA sequence- 1523 base pairs
      (bp) upstream from the start of PAI-1 gene transcription to +90 bp in the first
      exon, were amplified by polymerase chain reaction and analyzed by single-strand
      conformation polymorphisms. Two polymorphisms were found: a previously described
      4G/5G deletion/insertion polymorphism -675bp upstream from the start of
      transcription and a novel G/A single base substitution polymorphism further
      upstream at -844 bp. The two polymorphisms were in strong linkage disequilibrium.
      Significant differences between patients and controls were observed neither for
      the frequencies of the 4G/5G alleles (0.60/0.40 and 0.59/0.41, respectively) nor
      for the frequencies of the G/A alleles (0.33/0.67 and 0.41/0.59, respectively).
      The distribution of both polymorphisms was similar in idiopathic and secondary
      DVT as well as in first and recurrent DVT. In patients association between the
      4G/5G genotypes and PAI activity was observed, with the highest values in the
      4G/4G genotype (13.3 U/mL), median values in the 4G/5G genotype (9.8 U/mL) and
      the lowest values in the 5G/5G genotype (2.0 U/mL). Despite the lack of
      association between the G/A genotypes and plasma PAI-1 levels, electrophoretic
      mobility shift assay showed specific binding of a nuclear protein from human
      vascular endothelial cells extracts to both the G and the A variant, suggesting
      functional importance of this novel G/A polymorphism in regulating the expression
      of PAI-1 gene.

PMID- 8987165
TI  - The effect of a 5HT2 receptor antagonist sarpogrelate (MCI-9042) treatment on
      platelet function in Buerger's disease.
AB  - The effect of a new, specific 5-HT2 receptor antagonist sarpogrelate (MCI-9042)
      treatment on platelet function and serotonin levels in both plasma and whole
      blood in Buerger's disease, was assessed in a pilot study. We investigated 10
      patients suffering from Buerger's disease. Sarpogrelate in a dose of 3 x 100 mg a
      day was given p.o. for a period of 8 weeks. It was well tolerated and no major
      side effects were noted. It was judged to be effective in some patients as
      assessed by its effect on both subjective complaints and objective evaluation of
      ankle pressure index (API). Sarpogrelate induced a significant decrease in plasma
      serotonin (5-HT) concentration starting after the 4th week which lasted through
      to the 8th week of the study, whereas plasma tryptophan concentration increased
      significantly after 2 and 4 weeks. There were no changes in plasma 5-HIAA
      concentration. On the other hand whole blood 5-HT concentration increased
      significantly after 2 weeks, and there was also a tendency to increase in whole
      blood tryptophan concentration (p = 0.052). Platelet aggregation induced by ADP
      and collagen did not show any statistically significant changes. Surprisingly,
      platelet aggregation induced by serotonin increased significantly after 2 weeks
      and even more so after 4 weeks of treatment, and then it returned to baseline
      values after 8 weeks. There was no effect on platelet count, APTT, TT and
      fibrinogen concentration.

PMID- 8987166
TI  - Characterisation of cell-surface procoagulant activities using a microcarrier
      model.
AB  - A novel model is described for characterisation of cell-surface procoagulant
      activities and their inhibitors. Microcarrier beads were used to present living
      cells to recalcified blood plasma in the stirred measuring wells of an
      electromagnetic coagulometer. By this means the procoagulant activity on the
      surface of the cells could be automatically determined as clotting time.
      Procoagulant activity was investigated on normal and transformed cells, and
      representing hemopoietic, endothelial, muscle and connective tissue phenotypes.
      The procoagulant activity on each cell type was characterised by the use of
      specifically immunodepleted plasmas and specific inhibitors, including monoclonal
      antibodies. The predominant cell surface trigger of coagulation found in this
      series was tissue factor, and only blood monocytes provided some evidence for
      direct activation of factor X independent of FVII. Human ECV304 transformed
      endothelial cells were more closely studied as representative of a cell type
      constitutively expressing procoagulant. Coagulation mediated by ECV304 cells was
      found to be strictly dependent on tissue factor, as shown by an inhibitory
      monoclonal antibody, and on coagulation factors V, VII and X. ECV304 procoagulant
      activity was strongly inhibited by active-site-inactivated FVIIa, a synthetic
      peptide inhibitor of FXa (Tenstop) and the thrombin inhibitor, hirudin. While not
      appropriate for routine clinical assessment of coagulation factor function, we
      have found this model to be valuable in characterising the procoagulant activity
      on different cell types and particularly useful as a drug discovery tool in the
      search for new anticoagulants.

PMID- 8987167
TI  - Trypsin induced von Willebrand factor release from human endothelial cells in
      mediated by PAR-2 activation.
AB  - Nystedt and co-workers cloned in 1994 a second protease activatable receptor (PAR
      2) that could be activated by trypsin but not by thrombin (1). In this study, we
      investigated whether trypsin induced stimulation of endothelial cells is linked
      to PAR-2 activation. We have found by mRNA analysis that endothelial cells of
      venous and arterial origin express both protease activatable receptors. The
      functional thrombin receptor and the protease activated receptor-2 (PAR-2)
      mediate apparently the same effects in human vascular endothelial cells. Both,
      the activation of the thrombin receptor with thrombin or SFLLRN and the
      activation of the PAR-2 with trypsin or SLIGRL induced intracellular calcium
      mobilisation and a subsequent release of von Willebrand factor (vWf) from Weibel
      Palade bodies. As a consequence, it can be concluded that endothelial cells have
      two different receptors mediating the same cellular responses after activation.

PMID- 8987168
TI  - The prostacyclin stimulating plasma factor activity improves thromboresistance
      only if vascular PGI2-production is intact.
AB  - PGI2 is important in regulating platelet vessel wall interaction (1). In
      perfusion chamber experiments the amount of PGI2 formed was inversely related to
      the amount of platelets deposited (2). In 1978 a plasma factor was described
      which stimulates vascular PGI2-production (3). In later years, this activity has
      been monitored in different patient groups (for review see 4). Interestingly, it
      has been found that diseases associated with an increased bleeding tendency such
      as uraemia (5) or hepatic failure (6) were associated with an increased PF
      activity while others with an enhanced thrombophilia sometimes show an absence of
      PF-activity (7). Recently, the PGI2 stimulating plasma factor has been purified
      and cloned (8). It was the aim of these experiments to assess whether PF-activity
      plays a role in local hemostasis regulation under in-vivo flow conditions and
      whether this is dependent on the presence of an intact PGI2-formation.

PMID- 8987169
TI  - Mn-superoxide dismutase from the halophilic halotolerant bacterium Ba1--isolation
      and active site spectroscopic studies.
AB  - The superoxide-dismutase (SOD) enzyme, isolated from the halophilic halotolerant
      bacterium Ba1, was found to be a dimer with a molecular weight of 40 kD and a
      subunit weight of 23.5 kD. The partial N-terminal sequence showed significant
      homology to SODs isolated from various sources. Metal analysis showed that SOD
      from Ba1 contains manganese and iron with the following stoichiometries: 0.9 +/-
      0.4 Mn/dimer and 0.6 +/- 0.2 Fe/dimer. Two bands were obtained by isoelectric
      focusing, at pI of 4.45 and at 4.40. Native SOD from Ba1 at room temperature was
      ESR silent. An ESR spectrum of hydrated Mn(II) was obtained from denaturated
      enzyme. Native enzyme cooled to 97 K showed an ESR spectrum identified as being
      due to Fe(III). The spectrum was pH-independent. SOD from Ba1 was not inactivated
      by H2O2. On the basis of these observations, SOD from Ba1 was characterized as
      MnSOD. The excitation fluorescence spectrum of SOD from Ba1 showed four main
      peaks in the visible region. The effects on the spectra of KSCN, NaN3, NaF, and
      ascorbate were examined. Measurements of H2(17)O-nmr relaxation times T1 and T2,
      for solutions containing E. coli MnSOD and FeSOD, showed no paramagnetic
      contribution. These results support the assumption that the water molecule at the
      active site is strongly bound.

PMID- 8987170
TI  - Physical characterization of a totally synthetic rubredoxin.
AB  - The entire polypeptide of hyperthermophilic Pyrococcus furiosus rubredoxin was
      synthesized in order to specifically probe structural determinants of protein
      thermostability. The uv-visible, circular dichroic, electron paramagnetic, and
      nuclear magnetic resonance spectra, and electrochemical properties, of the native
      and synthetic proteins were essentially identical. The synthetic protein had a
      half-life for denaturation of 24 hr at 80 degrees C. The synthetic protein is
      considerably more thermostable than nonhyperthermophilic rubredoxins, but not as
      stable as the native protein. Based on the spectroscopic evidence, it appears
      that the synthetic protein is incorporating iron properly to form holoprotein,
      but the peptide still may not be folded correctly.

PMID- 8987171
TI  - The influence of trace elements on calcium phosphate formation by matrix
      vesicles.
AB  - The effects of two inhibitors, fluoride (F-) and zinc (Zn2+), were studied on the
      formation of mineral by matrix vesicles (MV) in an in vitro system. Kinetically,
      mineral formation by MV incubated in a synthetic cartilage lymph (SCL) is
      characterized by three phases: a lag period, a period of rapid uptake, and
      finally a period of slow uptake. Zn2+ at > or = 5 microM completely inhibited MV
      mineralization; at < or = 1 microM, it had little effect on rate of ion uptake,
      but delayed conversion of an OCP-like intermediate into hydroxyapatite (OHAp). F-
      at > or = 10 microM reduced the rate of rapid uptake by MV and caused the OCP
      like precursor to convert to OHAp. When synthetic OCP was seeded into SCL,
      mineralization ensued and OHAp became the dominant phase. With Zn2+ present, OCP
      like features persisted longer; with F-, the OCP-like features were lost more
      rapidly. When ACP was seeded into SCL, OHAp formed; Zn2+ at < or = 1 microM
      caused OCP-like mineral to form. Our findings indicate that Zn2+ stabilizes a
      noncrystalline precursor in MV regulating the length of the lag period; Zn2+ also
      favors the formation of an OCP-like intermediate whose growth accounts for the
      rapid uptake phase. This OCP-like phase appears to nucleate formation of OHAp by
      MV.

PMID- 8987172
TI  - A history of studies of visual accommodation in birds.
AB  - Since 1813, when Crampton first described the ciliary muscle of the avian eye,
      there has been little agreement on how birds are able to change the focus of
      their eyes. Numerous later studies on the eyes of a variety of bird species
      contradicted earlier findings or proposed new accommodative mechanisms. The
      resulting confusion persists today, and a number of significant works on the
      avian eye perpetuate many of the myths developed during the 1800s. There is
      little consensus on avian accommodation; the early literature contains many
      accurate descriptions of the mechanisms, along with elegant experimental evidence
      to support them. Much of the early literature, however, is in German and has
      remained obscure. Further, among the mechanistic descriptions of avian
      accommodation are many that are incorrect. The current confusion can be
      attributed in part to the fact that some birds have both corneal and lenticular
      accommodation. It is unclear to what extent different bird species employ both
      mechanisms, or depend on one mechanism or the other. These facts, together with
      the diversity of bird species, their range of visual requirements, and the
      numerous anatomical differences in their eyes, make it impossible to describe a
      single avian mechanism of accommodation. Our own experience in studying
      accommodation in the chick eye has led us to review the historical literature in
      an attempt to provide a new foundation for future studies on visual accommodation
      in birds. While in relation to the anatomical arrangements [of the bird eye],
      these have led our knowledge pretty much to a conclusion.... There is among all
      these works no real difference of opinion. However, in terms of the accommodative
      mechanism of the bird eye, at the present time there are many different views of
      what is going on. Here the circumstances are very similar to what happened a few
      decades ago in the study of accommodation generally, but particularly with
      humans, when Helmholtz made the remark. "There is no other portion of
      physiological optics in which one finds so many differing and contradictory ideas
      us in the accommodation of the eye, where we have only recently actually made
      observations on what previously was left to the play of hypotheses".

PMID- 8987173
TI  - Seasonal changes in immune function.
AB  - Winter is energetically demanding. Physiological and behavioral adaptations have
      evolved among nontropical animals to cope with winter because thermoregulatory
      demands increase when food availability decreases. Seasonal breeding is central
      within the suite of winter adaptations among small animals. Presumably,
      reproductive inhibition during winter conserves energy at a time when the adds of
      producing viable young are low. In addition to the well-studied seasonal cycles
      of mating and birth, there are also significant seasonal cycles of illness and
      death among many populations of mammals and birds in the field. Challenging
      winter conditions, such as low ambient temperatures and decreased food
      availability, can directly induce death via hypothermia, starvation or shock. In
      some cases, survival in demanding winter conditions puts individuals under great
      physiological stress, defined here as an adaptive process that results in
      elevated blood levels of glucocorticoids. The stress of coping with energetically
      demanding conditions can also indirectly cause illness and death by compromising
      immune function. Presumably, the increased blood concentrations of adrenocortical
      steroids in response to winter stressors compromise immune function and
      accelerate catabolic mechanisms in the field, although the physiological effects
      of elevated glucocorticoids induced by artificial stressors have been
      investigated primarily in the laboratory. However, recurrent environmental
      stressors could reduce survival if they evoke persistent glucocorticoid
      secretion. The working hypothesis of this article is that mechanisms have evolved
      in some animals to combat seasonal stress-induced immunocompromise as a temporal
      adaptation to promote survival. Furthermore, we hypothesize that mechanisms have
      evolved that allow individuals to anticipate periods of immunologically
      challenging conditions, and to cope with these seasonal health-threatening
      conditions. The primary environmental cue that permits physiological anticipation
      of season is the daily photoperiod; however, other environmental factors may
      interact with photoperiod to affect immune function and disease processes. The
      evidence for seasonal fluctuations in lymphatic organ size, structure, immune
      function, and disease processes, and their possible interactions with recurrent
      environmental stressors, is reviewed. Seasonal peaks of lymphatic organ size and
      structure generally occur in late autumn or early winter and seasonal minima are
      observed prior to the onset of breeding. Although many of the field data suggest
      that immune function and disease processes are also enhanced during the winter,
      the opposite seasonal pattern is also observed in some studies. We propose that
      compromised immune function may be observed in some populations during
      particularly harsh winters when stressors override the enhancement of immune
      function evoked by short day lengths. Because so many factors covary in field
      studies, assessment of our proposal that photoperiod mediates seasonal changes in
      immune function requires laboratory studies in which only photoperiod is varied.
      A review of the effects of photoperiod on immune function in laboratory studies
      reveals that exposure to short day lengths enhances immune function in every
      species examined. Short day exposure in small mammals causes reproductive
      inhibition and concomitant reduction in plasma levels of prolactin and steroid
      hormones, as well as alterations in the temporal pattern of pineal melatonin
      secretion. These hormones affect immune function, and influence the development
      of opportunistic diseases, including cancer: however, it appears that either
      prolactin or melatonin secretion is responsible for mediating the effects of
      photoperiod on immune function. Taken together, day length appears to affect
      immune function in many species, including animals that typically do not exhibit
      reproductive responsiveness to day length.

PMID- 8987174
TI  - Pathophysiology of cholesterol gallstone disease.
AB  - The purpose of the present paper is to review the current knowledge about
      cholesterol gallstone disease. It is generally accepted that the formation of
      cholesterol gallstone requires three major pathogenic defects, namely,
      supersaturation, nucleation and crystal growth as well as disorder of gallbladder
      motility. The supersaturation is necessary but not sufficient to explain stone
      formation. It has been suggested that nucleation is the key factor for gallstone
      formation. However, those three factors are necessary for the formation of
      cholesterol gallstones, and the presence of just one or two factors does not lead
      to stones. We also touch briefly on the results from studies performed in Mexico
      in this area.

PMID- 8987175
TI  - Alanine aminotransferase activity in mammary tissue, muscle and liver of dam rat
      during lactation and weaning.
AB  - Transamination reaction is the first step in the catabolism of most of the L
      amino acids. Alanine is an important molecule in the inter-organ nitrogen
      transport, conveying them from muscle to the liver. Amino groups from this amino
      acid are generally first transferred to alpha-ketoglutarate in the cytosol of
      liver cells to form glutamate and leaving behind the corresponding alpha-keto
      acid analog. Measurements of the alanine aminotransferase (EC2.6.1.2.) activity
      were compared in liver, mammary gland and skeletal muscle in virgin, lactating
      and weaning dam rats. In this study liver was the principal tissue involved in
      alanine transamination, while muscle showed a reduction in the enzyme activity
      during lactation. Results indicate an increase in alanine amino-transferase
      activity in the mammary gland during lactation and weaning when compared with
      virgin rats. This suggests that mammary gland during lactation is an important
      extra-hepatic tissue involved in the metabolism of alanine and probably shunted
      into the pathways for amino group metabolism in terms of nitrogen economy.

PMID- 8987176
TI  - Changes in transition metal contents in rat brain regions after in vivo
      quinolinate intrastriatal administration.
AB  - Total copper and manganese contents were measured in five rat brain regions 7
      days after a unilateral striatal injection of quinolinic acid (QUIN, 240 nmol/ 1
      microliter), an endogenous N-methyl-D-aspartate (NMDA) receptor agonist.
      Concentrations of both transition metals were evaluated in tissue of brain
      cortex, hippocampus, corpus striatum, midbrain and cerebellum of saline- and QUIN
      treated rats using graphite furnace atomic absorption spectrophotometry.
      Increases in copper content were observed after QUIN striatal injection in
      cerebellum, hippocampus, midbrain and corpus striatum (37, 55, 71 and 152% as
      compared against control values, respectively) but not in brain cortex. Manganese
      levels were found enhanced only in corpus striatum of QUIN-treated rats by 35%
      vs. control values, but not in all other brain regions analyzed. QUIN-induced
      increases in regional copper content were partially prevented in hippocampus,
      midbrain and striatum (17, 57, and 23% vs. control, respectively) by pretreatment
      of rats with an NMDA receptor antagonist, dizocilpine (MK-801, 10 mg/kg, i.p.),
      administered 60 min before QUIN microinjection. The same protective effect of
      dizocilpine was observed against QUIN-induced enhancement of striatal manganese
      content (-0.45% vs. control). These findings resemble those changes observed in
      postmortem Huntington's disease brains and suggest that alterations in regional
      content of copper, but not in manganese, may be a consequence of the spreading of
      QUIN-induced neurotoxic events into the striatal tissue to the neighboring
      regions of the brain, by action of QUIN on NMDA receptors.

PMID- 8987177
TI  - Comparison between Sprague-Dawley and Wistar rats as an experimental model of
      pharmacokinetic alterations induced by spinal cord injury.
AB  - Two strains of rats, Sprague-Dawley and Wistar, were assayed in order to
      determine which strain is the more suitable experimental model for the study of
      pharmacokinetic alterations induced by spinal cord injury. Animals were submitted
      to spinal cord contusion at the T8-T9 level by the weight drop method. A single
      acetaminophen oral dose (100 mg/ kg) was administered 24 h after injury and blood
      samples were drawn for a period of 4 h. Acetaminophen concentration in whole
      blood was determined by high performance liquid chromatography and
      pharmacokinetic parameters were estimated. For both strains, Cmax and AUC were
      significantly lower, whereas tmax remained unchanged, in injured animals compared
      to sham-injured controls. Circulating acetaminophen concentrations were higher;
      therefore, pharmacokinetic alterations were more easily discerned, in Sprague
      Dawley than in Wistar rats. It is concluded that the Sprague-Dawley strain is a
      more suitable model for the study of pharmacokinetic alterations induced by
      spinal cord injury.

PMID- 8987178
TI  - Flow cytometry evaluation of complement mediated bacterial membrane damage.
AB  - The study of the complement-outer bacterial membrane interactions is gaining
      enthusiasm for applying a continuous development of more specialized techniques.
      In this paper a novel flow cytometry technique shows that highly fluorescent
      lucifer yellow-stained Neisseriae gonorrhoeae when exposed to the redox reaction
      of p-nitro blue chloride tetrazolium (NBT), as formazan precipitation takes
      place, a shift to lesser fluorescent channels of the histogram population occurs.
      That effect is labeled NBT-laser beam quenching (NBT-LBQ). A significant
      difference by Kolmogorov-Smirnov summation curve analysis is found between
      complement heat-inactivated and its counterpart assessed with normal complement
      microorganisms. The operation of this NBT-LBQ effect by microbial flow cytometry
      casts an interesting potential for the evaluation of the outer membrane
      complement-interaction of serum sensitive microorganisms.

PMID- 8987179
TI  - Gangliosides minimize motor disabilities and histopathological changes in
      cortical lesioned and transplanted rats.
AB  - The effect of bovine brain gangliosides was studied in rats lesioned by partial
      suction of the right somatosensory cortex and also in rats implanted with a piece
      of fetal brain tissue in this area. In both experiments a group of animals
      received 30 mg/kg i.p. of gangliosides daily for a period of 7 days after
      surgery. In lesioned rats, the untreated group showed a lower maintenance on a
      tight rope test at 7 as well as at 14 days, as compared with a sham-operated
      group (p < 0.05). In transplanted rats ganglioside treatment prevented the
      increase of the probability of falls from a horizontal bar at days 7 and 14 post
      operations and the probability of slips on a vertical bar at day 7 (p < 0.05).
      Rats were killed at day 15 and brain coronal sections were obtained. Nuclear area
      and circularity were measured in a sample of cortical and grafted cells in a
      computer aid-image analyzer. Ganglioside protection on the normal size and shape
      of the nuclei in the ipsilateral cortex in lesioned as well as in transplanted
      rats (p < 0.01) was found. A higher nuclear area in ganglioside than in saline
      treated grafts was noted. Results suggest a protective action of the gangliosides
      against the lesion-induced motor dysfunction and secondary cortical cell
      degeneration.

PMID- 8987180
TI  - Induction of macrophage killing of Leishmania donovani by human CD4+ T cell
      clones.
AB  - Immunity in leishmaniasis is mediated by T cells, but protective responses in
      humans have not been fully defined. In this study, the functional activity of
      CD4+ T cell clones derived from an immune individual was investigated to identify
      potentially protective responses. The T cells proliferated and produced
      interferon-gamma (IFN-gamma) in response to a soluble Leishmania donovani antigen
      extract and live amastigotes. There was considerable variation in the anti
      leishmanial activity of the T cell clones when they were co-cultured with L.
      donovani infected monocytes isolated from an HLA-DR,DQ matched donor. All of the
      clones which demonstrated antigen specific reactivity by proliferation or
      cytokine production induced some degree of inhibition of intracellular parasite
      replication, but only a few of the clones induced pronounced leishmanicidal
      activity. There was strong correlation between the level of amastigote-induced
      IFN-gamma secretion and anti-leishmanial activity. This approach enables the
      identification of potentially protective immune responses in humans at the clonal
      level, and offers a means for the identification of the relevant antigen(s).

PMID- 8987181
TI  - Technetium-99m-alendronate: a new radiopharmaceutical for bone scanning.
AB  - The purpose of this paper is to report the preparation of a new technetium-99m
      radiopharmaceutical for bone scanning. The chelating agent for 99mTc is a new
      bisphosphonate, alendronate, 4-amino-1-hydroxy-butylidene-1, 1-bisphosphonate
      (ABP) used as a treatment for osteoporosis. ABP, because of its amino group,
      seems to be better suited to form a strong and stable complex with technetium-99m
      and therefore might be better than 99mTc-etidronate (HEDP) or 99mTc-medronate
      (MDP) for bone scanning. A sterile dry kit containing APB, a reducing agent and a
      stabilizer was prepared. The parameters studied were molar concentrations, pH,
      shelf life, labeling efficiency and radiochemical purity. The oven dried sterile
      kit was formulated with 5 mg ABP, 0.25 mg stannous fluoride and 0.025 mg gentisic
      acid at pH 2.5-3.5. The labeling efficiency with 20-1500 MBq of pertechnetate
      (99mTcO4-) was over 95% at room temperature and was stable for 5 h. Technetium
      99m-alendronate was tested in two rabbits and it proved to be a promising new
      radiopharmaceutical for bone scanning. Work is underway to study 99mTc-ABP
      biodistribution in a statistically significant number of laboratory animals and,
      later on, to determine radiopharmacokinetic parameters in normal volunteers.

PMID- 8987182
TI  - Carbamazepine poisoning in adolescent suicide attempters. Effectiveness of
      multiple-dose activated charcoal in enhancing carbamazepine elimination.
AB  - The aim of the study was to evaluate continuous administration of multiple-dose
      activated charcoal (MDAC) in enhancing elimination of carbamazepine (CBZ) in
      eight consecutive adolescent suicide attempters. Diluted charcoal was
      administered through a nasogastric tube at a dose of 1 g/kg every 4 h, and a
      saline cathartic at the same dosage was administered every 12 h. Plasma CBZ
      concentrations were measured at 0.0, 12, 24 and 36 h by means of a modified EMIT
      technique. As a measure of CBZ disappearance, half life of elimination (t1/2
      beta) and exogenous total body clearance (CLB) were calculated. Clinical
      improvement occurred after 12 to 24 h, except in one patient who was the most
      severely intoxicated and who required advanced life-support therapy.
      Pharmacokinetic data reported a mean t1/2 beta of 9.5 h, shorter than the
      reference value of 18-54 h (p < 0.05), and a mean CLB of 103.13 ml/ min/kg,
      higher than the reference of 75.01 ml/min/ kg (p < 0.05). Initial mean CBZ levels
      of 27.9 decreased to 0.82 microgram/ml (97% of elimination, p < 0.05). MDAC was
      free from adverse side effects. In conclusion, MDAC is an effective procedure in
      enhancing CBZ elimination in overdosed patients as well as being relatively free
      from serious side effects, widely available, inexpensive and non-invasive.

PMID- 8987183
TI  - Double mitral valve orifice. Two-dimensional and Doppler echocardiographic
      diagnosis.
AB  - The purpose of this study was to demonstrate the usefulness of two-dimensional
      and Doppler echocardiography for diagnosing double mitral valve orifices (DMVO)
      in addition to identifying associated pathologies. We report five cases, three
      male and two female with an age ranging from 4 to 44 years old (mean age: 17
      years), with the diagnosis of DMVO according to the following characteristics:
      using two-dimensional echocardiography on the short parasternal axis, both
      orifices were observed; apical in which the "seagull sign" was identified in both
      chambers, in addition to identifying the flows of each orifice by pulsed and
      codified color Doppler obtaining the corresponding gradients. With respect to the
      associated pathologies, all patients presented some type of malformation, such as
      subaortic ring, patent ductus arteriosus, coarctation of the aorta, bicuspid
      aorta and pulmonary stenosis. Using the color Doppler echocardiography allows an
      adequate anatomical and functional definition of DMVO.

PMID- 8987185
TI  - Effects of occupational exposure to mercury vapors on T-cell and NK-cell
      populations.
AB  - The counts of lymphocytes, (CD3+) T-cells, (CD4+) T-helper and (CD 8+) T
      suppressor and (CD 16+) NK-cells were determined in the peripheral blood of 81
      males with a history of occupational exposure to metallic mercury vapors and in
      36 males without this exposure. For the determination of T-cell populations
      monoclonal antibodies were used in indirect immunofluorescence tests. The
      weighted mean of mercury concentrations in air was 0.028 mg x m-3. Mercury
      concentration in the urine of the exposed subjects ranged from 10-240 micrograms
      x l-1, and in blood it was from 4-30 micrograms x l-1. Stimulation of the T-cell
      line was noted as evidenced by increased number of T-cells by 35% in the workers
      with exposure to mercury vapors below or by 38% in the workers over 10-years, by
      increased number of T-helper cells by 42% (p < 0.001) in the workers with
      exposure below or by 60% (p < 0.001) in the workers over 10 years and by
      increased number of T-suppressor cells by 85% (p < 0.001) in the workers below or
      by 96% (p < 0.001) in the workers over 10 years exposure. Lower increase of T
      helper cells population than T-suppressor cells population was the cause of
      decreased value of the T-helper/T-suppressor ratio by about 21% (p < 0.01) in the
      workers with exposure below and over 10 years. No changes were observed in the T
      cell populations between workers with up to 10 and those with over 10 years
      exposure. The quantitative changes of T-helper cells and T-helper/T-suppressor
      ratio may represent an immunological indicator of exposure to mercury vapors.
      Presented changes in human T-lymphocytes population associated with occupational
      exposure to mercury vapors have been proposed to explain the origin of more
      frequent autoimmunity induced by mercury.

PMID- 8987184
TI  - Effects of diazepam on fentanyl-induced epileptoid EEG activity and increase of
      multineuronal firing in limbic and mesencephalic brain structures.
AB  - Electroencephalographic and clinical signs of epileptoid activity have been
      associated with the administration of fentanyl during surgery in patients. These
      phenomena have been in turn related to changes in metabolic rate, oxygen
      consumption, and blood flow in specific brain structures both in humans and
      experimental animals. However, direct evidence showing changes in neuronal firing
      in specific brain regions during fentanyl-induced epileptoid activity has not
      been reported. Eight adult male cats with chronically implanted bipolar
      electrodes in the mesencephalic reticular formation, hippocampus, amygdala, and
      parieto-occipital cortex were included in the study. Different treatments, i.e.,
      vehicle-fentanyl or diazepam-fentanyl, were administered to the experimental
      animals at 7-day intervals under neuromuscular blockade and assisted ventilation.
      Electroencephalographic (EEG) seizures, grouped and isolated spikes, and
      significant increases of multineuronal activity (MUA) were elicited by fentanyl,
      50 micrograms/kg iv, in these brain structures. Both EEG and MUA changes reached
      their maximal values within 6 min of fentanyl administration, and then diminished
      as time elapsed. Diazepam, 100, 200, or 400 micrograms/kg, but not 50
      micrograms/kg iv, significantly reduced or prevented the fentanyl-induced
      epileptoid EEG activity and MUA increases. The present results show that both
      fentanyl-induced epileptoid EEG activity as well as the concomitant increase in
      MUA of brain subcortical structures are part of the same epileptogenic
      phenomenon, mainly generated at limbic structures. In addition, the effects of
      diazepam against both epileptoid EEG activity and increase of MUA of brain
      subcortical structures support the use of benzodiazepines as premedicants for
      fentanyl anesthesia in order to prevent or to reduce epileptoid phenomena that
      can result from opioid administration during the anesthetic procedures.

PMID- 8987186
TI  - Electro-oculographic recordings reveal reading deficiencies in learning disabled
      children.
AB  - This study was undertaken in order to learn the functional differences in reading
      tasks between two groups of children: those identified as learning disabled and a
      group of control children. During the earliest stages of learning to read,
      children adopt a logographic strategy, in which letter order is ignored and
      phonologic factors are secondary. The children later move into an alphabetic and
      then to an orthographic reading stage. Reading strategies can be studied by
      electro-oculographic (EOG) recordings during text reading. This investigation
      uses EOG to study text reading time, and number of saccadic and regressive
      movements, to test if learning disabled children show altered strategies on text
      reading. Nineteen learning disabled and thirteen control subjects were included
      in the study. Learning disabled children showed longer text reading time, and
      greater number of saccadic and regressive eye movements. Electro-oculographic
      recording is not a test customarily performed on learning disabled children.
      However, our results concerning the dynamic discriminative reading have shown
      that it can be a useful tool for the examination of learning disabled children.

PMID- 8987187
TI  - Humoral and cellular immune response within the subarachnoid space of patients
      with neurocysticercosis.
AB  - To study the immune response within the subarachnoid space in patients with
      neurocysticercosis, we measured the cerebrospinal fluid contents of
      immunoglobulins A, E, G, and M in 38 patients and the contents of the
      proinflammatory cytokines TNF-alpha, IL-1b, IL-6 and IFN-gamma in 17 patients.
      The same measurements were made in 30 neurological patients without inflammatory
      or immune-mediated disorders. Each immunoglobulin and cytokine, including the
      gender and age of the patient, was compared by multiple regression analysis with
      the CSF contents of cells, protein and ELISA for cysticercal antigens. A direct
      correlation was found of IgM with cell content (p < 0.058) and with ELISA values
      (p < 0.027); of age with protein content (p < 0.006); of IL-6 with protein
      content (p < 0.018) and of IL-1b with ELISA values (p < 0.004). An inverse
      correlation was found of glucose with ELISA values (p < 0.008). A complex
      function of the immune response within the subarachnoid space was observed: mean
      values of IgG, IgM, IgE and interleukins 1b and 6 were increased, whereas values
      of IgA, TNF-alpha and IFN-gamma were similar to those of controls.

PMID- 8987188
TI  - Monounsaturated fatty acid (avocado) rich diet for mild hypercholesterolemia.
AB  - To assess the effect of a high monounsaturated fatty acids (MFA) diet on serum
      lipids, 30 healthy adult normolipidemic volunteers and 37 adult patients with
      mild hypercholesterolemia (5.4-9.3 mmol/l), 15 of them also with
      hypertriglyceridemia (2.3-4.8 mmol/l), were studied. Fifteen healthy and 30
      hypercholesterolemic subjects (15 of them with associated type 2 diabetes
      mellitus) received an avocado enriched diet (2000 Kcal, lipids 53% MFA 49 g
      saturated/unsaturated ratio 0.54), and seven non-diabetic hypercholesterolemic
      individuals received an isocaloric control diet (MFA 34 g, saturated/unsaturated
      ratio 0.7). Serum total cholesterol, LDL-cholesterol, HDL-cholesterol and
      triglyceride concentrations were measured before and after a 7-day diet period.
      In healthy individuals a 16% decrease of serum total cholesterol level followed
      the high MFA diet, while it rose after the control diet (p < 0.001 between
      diets). In hypercholesterolemic subjects a significant (p < 0.01) decrease of
      serum total cholesterol (17%), LDL-cholesterol (22%) and triglycerides (22%), and
      increase of HDL-cholesterol (11%) levels occurred with the avocado diet, while no
      significant changes were noticed with the control diet. High lipid, high MFA
      avocado enriched diet can improve lipid profile in healthy and especially in mild
      hypercholesterolemic patients, even if hypertriglyceridemia (combined
      hyperlipidemia) is present.

PMID- 8987189
TI  - Nortriptyline-fluphenazine vs. carbamazepine in the symptomatic treatment of
      diabetic neuropathy.
AB  - We compared the efficacy and tolerance of the combination of nortriptyline
      fluphenazine (NF) vs. carbamazepine (CMZ) in the symptomatic therapy of patients
      with severe, distal, symmetrical, predominantly sensitive diabetic polyneuropathy
      (DPN). We followed a double blind, crossover, randomized and double placebo
      design. Sixteen patients with severe DPN participated in the study. Patients
      received either NF (1 tablet three times a day (tid)), for 2 weeks and 2 tablets
      tid for the next 2 weeks or CMZ 1/2 tablet tid for 2 weeks and 1 tablet tid for
      the next 2 weeks. After this, patients received placebos of both drugs (wash-out
      period), until symptoms returned to baseline levels (100%), then they were
      crossed over to receive the other comparing drug schedule. A visual analogue
      scale was used to evaluate the percent changes in pain and paresthesia. HbA1,
      fasting serum glucose, and safety tests were performed at 2- and 4-week
      intervals, respectively. Both therapies produced significant improvement of both
      pain and paresthesia. No statistically significant differences were observed
      between both therapies for either pain or paresthesia. No significant biochemical
      changes were observed with any of the two therapies. Side effects were mild and
      more frequent in the NF period. In this study no superiority of either drug
      schedule was demonstrated; therefore, the decision to use any of them should be
      made according to the associated pathology and potential side effects of each
      drug.

PMID- 8987190
TI  - Pattern-visual evoked potentials in thinner abusers.
AB  - Organic solvents cause injury to lipids of neuronal and glial membranes. A well
      known characteristic of workers exposed to thinner is optic neuropathy. We
      decided to look for neurophysiologic signs of visual damage in patients
      identified as thinner abusers. Pattern reversal visual evoked potentials was
      performed on 34 thinner abuser patients and 30 controls. P-100 wave latency was
      found to be longer on abuser than control subjects. Results show the possibility
      of central alterations on thinner abusers despite absence of clinical symptoms.

PMID- 8987191
TI  - Treatment of endometriosis with cyproterone acetate. Preliminary report.
AB  - The objective of this work was to evaluate the effectiveness of cyproterone
      acetate for the treatment of endometriosis. Seven patients with dysmenorrhea due
      to endometriosis and idiopathic hirsutism were included. Endometriosis was
      laparoscopically classified as minimal in two cases, mild in two, moderate in two
      and severe in one patient. Cyproterone acetate was initiated at a daily dose of
      10 mg orally for 20 days, followed by 10 days without medication. This sequence
      was repeated over a period of 6 months. Dysmenorrhea improved in all study
      subjects. Menstrual disorders were observed in all women, with oligomenorrhea in
      six patients and spotting in one. At the end of treatment, a second look
      laparascopy revealed minimal endometriosis in five patients and no evidence of
      the disease in the other two cases. Hirsutism was slightly reduced in two
      patients and without changes in the other five. These preliminary data disclose
      the possible therapeutic use of cyproterone acetate in endometriosis.

PMID- 8987192
TI  - Antibody response of Mexican infants to Haemophilus influenzae type b capsular
      polyribosylribitol phosphate. Differences between natural and vaccine induced
      (oligosaccharide-CRM197 conjugated vaccine) immunization.
AB  - In this study we compared natural vs. induced Haemophilus influenzae type b (Hib)
      anti-capsular polyribosylribitol phosphate (PRP) antibody response in a low
      socioeconomic population. One hundred twenty five 2-month-old children received
      the complete HbOC vaccine immunization scheme and a booster dose at 15 months of
      age. One hundred twenty five non-immunized children served as the control group.
      Serum Hib anti-PRP antibody titers were determined by ELISA in all children. We
      found at the end of the primary immunization scheme an antibody concentration of
      27.28 micrograms/ml in the immunized group vs. 7.48 micrograms/ml in the control
      group. The antibody response was mainly of the IgG1 class in both groups. After
      the booster dose the antibody concentration was 30.14 g/ml in the vaccinated
      group vs. 6.06 micrograms/ml in the control group (p < 0.01). Ninety nine percent
      of immunized and non-immunized infants had titers greater than 1 microgram/ml.
      These results confirm that immunization with the HbOC vaccine induces an
      important increase in anti-PRP specific antibody titer, but they also demonstrate
      that natural exposure induces responses higher than those referred as protective
      (1 microgram/ml).

PMID- 8987193
TI  - Blood lead concentrations and associated factors in residents of Monterrey,
      Mexico.
AB  - Data from interviews of 469 random subjects living in Monterrey, Nuevo Leon,
      Mexico were analyzed to investigate factors associated with blood lead (PbB). The
      following criteria were considered: age, sex, residence zone, occupation,
      smoking, alcohol consumption, and the use of glazed pottery. Multiple linear
      regression analysis disclosed that PbB concentration was significantly higher in
      males, in residents of northeastern (NE) Monterrey, and in blue-collar workers.
      The highest atmospheric lead (PbA) concentrations of all Monterrey were also
      found in the NE, the zone that contains the greatest density of factories within
      the city. PbB and PbA means were significantly correlated (r = 0.964) with regard
      to the four urban zones considered. It is concluded that increased PbB level in
      specific categories is probably explained by exposure to PbA originating from
      industrial emissions.

PMID- 8987194
TI  - PRISM score evaluation to predict outcome in pediatric patients on admission at
      an emergency department.
AB  - This study was undertaken in order to evaluate for the first time the usefulness
      of PRISM score to predict outcome in pediatric patients in the Intensive Care
      Area of the Emergency Department at the Instituto Nacional de Pediatria in Mexico
      City. A prolective evaluation of PRISM score was done using 100 consecutive
      pediatric patients admitted to INP-ED between July and November 1992 and
      considered critically ill by the attending pediatricians to calculate by a lineal
      logistic model the expected mortality and compare with the observed one. Using a
      cut-off of r = 0, we evaluated at the same time the sensitivity, specificity and
      efficiency of this score. Fifty-eight patients were male and 42 were female. The
      mean age was 51 months with a range of 3 days -192 months. PRISM score for
      survivors was in general 8.7 +/- 7.2 and 25.8 +/- 14 for nonsurvivors (p <
      0.001). Based on the logistic regression coefficients defined by Pollack et al.,
      our sample of 100 patients was estimated to expect 12.91 deaths whereas in fact
      11 were observed. Inspection of the survival rates across the different
      categories of expected mortality showed agreement and consistency in relation to
      original reports (9). The sensitivity, specificity and efficiency in general were
      1.0, 0.98 and 0.98, respectively. The PRISM is an objective and efficient method
      which helps physicians to predict patients' outcome and risk of mortality,
      providing the medical staff with an epidemiological criteria. Additionally, it
      may be helpful in decision-making for ICU admissions and correct identification
      of patients who can benefit from that level of care.

PMID- 8987195
TI  - Salt intake and blood pressure in rural and metropolitan Mexico.
AB  - A selected group of 155 Mexican adults aged 20-64 years were studied to
      investigate the role of sodium (Na) intake in explaining blood pressure (BP)
      differences in a rural town and urban Mexico City. The subjects had their BP,
      height, weight and skinfolds measured and they collected 3 continuous 24 h
      urines. Adjusted for age differences, average BPs were significantly higher (p <
      .05) for the urban (112.7 systolic: 73.6 diastolic mmHg) than for the rural group
      (108.4 systolic: 70.8 diastolic mmHg). They were also higher for men (111.8
      systolic: 74.3 diastolic mmHg) than for women (109.6 systolic: 70.2 diastolic
      mmHg), the diastolic BP difference being significant (p < 0.05). The average
      daily Na excretion was also higher in the urban (122.2 mmol/day) than in the
      rural community (98.0 mmol/day) (p < 0.01). Potassium excretion rates showed
      similar differences. The differences in sodium excretion and blood pressure among
      communities were particularly marked in those over 30 years of age. The means for
      the four community-sex groups had the same rank order for both BP and Na.
      However, although some large surveys have suggested that half the observed
      differences in BP might be explained by different Na intakes, in this study the
      relationship between Na excretion and BP did not achieve statistical
      significance. Differences in the body mass index (BMI) accounted for 41% of the
      observed variance in BP.

PMID- 8987196
TI  - Comparable growth of a Trichomonas vaginalis strain in PEHPS and TYI-S-33 media.
AB  - PEHPS medium, developed for axenic cultivation of Entamoeba histolytica and E.
      invadens, was also capable of supporting the growth of a Trichomonas vaginalis
      strain, with an inoculum of 1 to 100 trichomonads/ml. The logarithmic growth
      phase in PEHPS or in TYI-S-33 medium lasted 72 h; yield (3.33 +/- 0.56 x 10(6)
      trichomonads/ml), duplication time (4.27 h), number of duplications (16.85), or
      increase ratio (33,328) in PEHPS medium showed no significant differences with
      those obtained in TYI-S-33 under similar culture conditions. Accordingly, PEHPS
      medium might be used for the axenic cultivation of T. vaginalis.

PMID- 8987197
TI  - Pvu II RFLPs of LDL receptor gene in normolipidemic subjects from Havana City.
AB  - Allele and genotype frequencies for Pvu II restriction fragment length
      polymorphism of LDL receptor gene were determined in 36 normolipidemic unrelated
      subjects from Havana City. The frequencies were similar to those reported for
      other populations.

PMID- 8987198
TI  - Recombination of epithelial root sheath and dental papilla cells in vitro.
AB  - Hertwig's epithelial root sheath (HERS) cells were isolated and recombined with
      ectomesenchymal cells in vitro utilizing extracellular matrix components as
      substrate. After 14 days in culture, HERS cells were differentiated and exhibited
      a stratified organization. These features resembled those observed in vivo as
      epithelial rests of Malassez. A mineralization process was also present in HERS
      cells, in which calcium salts were deposited. This mineralization was correlated
      with the strong immunoexpression of osteopontin by HERS. The results obtained add
      support to the possible role of HERS in the secretion of hypocalcified material
      on the root during early cementogenesis.

PMID- 8987199
TI  - Hartmannella vermiformis isolated from the cerebrospinal fluid of a young male
      patient with meningoencephalitis and bronchopneumonia.
AB  - Meningoencephalitis and bronchopneumonia were documented in a patient from
      Peubla, Mexico. The patient began with symptoms and signs of a common flu and 12
      days after the onset of his disease he was admitted to the hospital presenting
      symptoms and signs of meningoencephalitis. The clinical course evolved into an
      endocraneal hypertension syndrome with bronchopneumonia, coma and death. Wide
      spectrum antibiotics, immunosuppressive and anti-tuberculosis therapy were
      unsuccessfully administered. Important antecedents were degree I malnutrition and
      repeated contact with polluted water. Post-mortem autopsy was not performed. Gram
      positive cocci were isolated from the spinal fluid 2 days after admission, and
      then active amebae were isolated from three different samples of the spinal fluid
      at days 16, 18 and 19 after admission. Such samples were concentrated and
      inoculated onto specific culture media. Identification of amebae was based on
      their morphology and biochemistry. All amebae were Hartmannella vermiformis.
      Amebae were apparently not the cause of the disease and might be considered as an
      opportunistic colonizer which may have caused the evolution of the disease to
      become worse.

PMID- 8987200
TI  - Fragile X studies and authorship.

PMID- 8987201
TI  - Advocating advocacy.

PMID- 8987202
TI  - Psychiatric nurses' knowledge of the Americans with Disabilities Act.
AB  - The Americans with Disabilities Act (ADA) provides civil rights protection for
      qualified individuals with disabilities. In spite of the protection afforded,
      people with serious and persistent mental illness may require advocates to help
      them benefit from the ADA. This descriptive investigation used primary data from
      900 psychiatric nurses to determine their knowledge of the ADA. Subjects were
      also asked to provide information about their clinical practice responsibilities,
      and how frequently they have provided clients, with ADA information. Results
      indicate that the majority of the psychiatric nurses in this study did not have
      the knowledge necessary to act as advocates with respect to the ADA. Moreover,
      few psychiatric nurses in the study had provided clients with ADA information.

PMID- 8987203
TI  - Cognitive theory applied to the treatment of delusions of schizophrenia.
AB  - This article reviews theory regarding cognitive interventions in schizophrenia,
      focusing particularly on the treatment of delusions. The cognitive theory of
      psychopathology is first introduced and the specific goals of cognitive therapy
      are then presented. A range of philosophical and etiologic perspectives on the
      nature of delusions are explored, including the cognitive perspective. Specific
      stages and techniques of therapy are discussed with theoretical underpinnings and
      suggestions for incorporation in advanced practice psychiatric nursing.

PMID- 8987205
TI  - Uncovering a world of mental illness: an analysis in perceptual transformation in
      undergraduate nursing students.
AB  - The culture of nursing education is a major influence in transforming student
      nurses' perceptions of mental illness and nurse educators are the primary
      facilitators in this process. Undergraduate nursing students' perceptions of
      mental illness change positively, however, it has not been understood how these
      changes occur. This pilot study extends understanding of how 22 undergraduate
      psychiatric nursing students' perceptions of mental illness became transformed
      during the course of one semester. The author analyzed student narratives using
      Heideggerian Hermeneutics. Five students, who wrote narratives, read a manuscript
      discussing the constitutive pattern and the relational themes and consensually
      validated the interpretation. The constitutive pattern that emerged is the
      Uncovering of Mental Illness. Three relational themes were identified that
      contributed to, and led to the development of the constitutive pattern. The three
      themes are (1) uncovering others' sameness through differences, (2) coming face
      to-face with mental illness, and (3) the staff nurse influence in the uncovering
      process. In addition to increasing understanding of perceptual transformation,
      the findings from this interpretation suggest that nurse educators can guide
      students in the development of therapeutic relationships by facilitating the
      uncovering process.

PMID- 8987204
TI  - Delayed recall of childhood sexual abuse: psychiatric nursing's responsibilities
      to clients.
AB  - In no other area of psychiatric care is such suspicion being cast on clients as
      in the area of delayed recall of childhood sexual abuse. Adult survivors of
      childhood abuse are encountered in nursing contexts of all kinds. Psychiatric
      nurses should be the ones that other nurses and members of the public can look to
      for guidance and clinical wisdom about dissociative amnesia for childhood abuse.
      It is incumbent on psychiatric nurses, especially those who publish about
      clinical issues, to provide the most accurate and complete available knowledge,
      to prioritize clients' needs, and to recommend care that meets the highest
      standards.

PMID- 8987206
TI  - Recent advances in the pharmacotherapy of major depression.
AB  - Major depression and its pharmacotherapy have changed substantially during the
      last decade. Several new agents have been approved for clinical use, and
      psychiatric nurses must be aware of the benefits and potential adverse reactions
      associated with each. Moreover, more than 40 states now grant prescriptive
      authority to advanced practice nurses, and psychiatric nurses need a thorough and
      balanced knowledge of these agents to initiate and monitor treatment
      appropriately. This review highlights key features of several newer
      antidepressants: three selective serotonin reuptake inhibitors approved for major
      depression (fluoxetine [Prozac, Dista, Indianapolis, IN], sertraline [Zoloft,
      Roerig, New York, NY], and paroxetine [Paxil, SmithKline Beecham, Philadelphia,
      PA]), a serotonin-norepinephrine reuptake inhibitor venlafaxine (Effexor, Wyeth
      Ayerst, Philadelphia, PA), and nefazodone (Serzone, Bristol-Myers Squibb,
      Princeton, NJ).

PMID- 8987207
TI  - A multinational study of psychiatric nursing staffs' beliefs and concerns about
      work safety and patient assault.
AB  - In an effort to understand beliefs and concerns about work safety and patient
      assault, the author describes the results of a multinational survey of 999
      nursing staff members working in psychiatric facilities across the United States,
      Canada, United Kindgom, and South Africa. Although the majority of the sample
      (75%) reported being physically assaulted at least once during their careers, 62%
      responded that they felt safe in their work environment most of the time.
      Significant differences were found among the nurses with regard to beliefs about
      adequacy of staffing, safety of the physical environment, admission of assaultive
      patients, expectations about being victims of assault, overall level of safety,
      and taking legal action against a patient. A significant difference in attitudes
      was also found among nursing staff members, who reported previous assaults. They
      believed that assaults are expected events in their work with psychiatric
      patients.

PMID- 8987208
TI  - Intersubjectivity, social microcosm, and the here-and-now in a support group for
      nurses.
AB  - Intersubjectivity, a concept from Watson's nursing model is interwoven with the
      group dynamics of social microcosm and the here-and-now. Examples from a graduate
      nursing student's clinical experience illustrate the application of a
      transpersonal dynamic, formerly associated with dyads, to interactions between a
      nurse and a support group. A psychiatric consultation liaison nurse specialist
      student facilitates a support group for registered nurses in a neurological
      intensive care unit, in response to a group-perceived need to improve
      communications between nurses, nurses and patients, and nurses and physicians.
      Discovery and processing of hidden anger and pain activates healing for these
      nurses.

PMID- 8987209
TI  - Genetic testing and public health.

PMID- 8987210
TI  - The international imperative.

PMID- 8987211
TI  - Haemolytic-uraemic syndrome: of sausages and legislation.

PMID- 8987212
TI  - Haemolytic-uraemic syndrome in the Hunter: public health implications.
AB  - Three cases of haemolytic-uraemic syndrome in the Hunter area were reported in
      February 1995. An investigation was initiated to identify any verocytotoxic
      Escherichia coli in clinical samples that could be associated with the
      development of the disease. Escherichia coli O6:H- and O2:H7 were isolated from
      Case 1. No organisms were identified for Case 2, and Case 3 samples yielded
      Campylobacter jejuni. In addition, efforts were made to trace sources of any such
      pathogens in food samples or in the environment generally. Shiga-like toxins were
      found in meat products sampled from butchers' shops patronised by the families of
      the three cases. However, it was not found possible to match stool samples with
      samples of food from sources used by the families of the children. Environmental
      factors seemed likely to have played a significant role in the development of
      haemolytic-uraemic syndrome in Case 3. It is suggested that the incidence of the
      disease may be reduced by increasing the frequency of testing of meat products
      for Shiga-like toxins I and II and through educational and research programs.

PMID- 8987213
TI  - Haemolytic-uraemic syndrome in Western Australia, 1980 to 1994.
AB  - A retrospective, population-based study of patients hospitalised with the
      haemolytic-uraemic syndrome in Western Australia from 1980 to 1994 was undertaken
      to describe the epidemiology of the disease in this state. We identified 41
      patients. Episodes were commonest in children under five years of age (63.4 per
      cent) and were more frequent in females (58.5 per cent) than in males; only one
      Aboriginal patient was detected. More than 90 per cent of episodes had a
      gastrointestinal prodrome lasting from one to 22 days; in 47.6 per cent of these
      episodes patients had bloody diarrhoea. The average hospital stay was 26 days,
      and 63.4 per cent of patients required dialysis (mean 10 days). More than 20 per
      cent of patients developed chronic renal failure, 9.7 per cent died, two patients
      developed hypertension and one child became epileptic; three of the 10 patients
      over 16 years of age (30 per cent) died. The haemolytic-uraemic syndrome is
      potentially fatal, affects mostly young children, and is usually preceded by a
      gastrointestinal illness. Episodes can occur in common-source outbreaks but, with
      the exceptions of related cases in families, that appears not to have been so in
      Western Australia since 1980. There is a need for increased awareness of the
      haemolytic-uraemic syndrome to enhance prospects for earlier detection and better
      clinical outcomes. Improved public health surveillance is also needed to reduce
      the risks of the syndrome in the community.

PMID- 8987214
TI  - Some public health issues in the current state of genetic testing for breast
      cancer in Australia.
AB  - Two genes associated with a high breast cancer risk (BRCA1 and BRCA2) have been
      discovered recently from study of large breast-cancer-dense kindreds. It is
      problematic to make inferences from these atypical families to the general
      population. Nevertheless, it appears that about 1 to 2 per cent of all breast
      cancer may be due to rare deleterious mutations in BRCA1 or BRCA2. The majority
      of breast cancer families with fewer than four cases are likely to have cancers
      not attributable to these genes. There may be more common mutations in other
      genes (such as ATM, HRAS1) that confer a moderate risk of breast cancer, and may
      account for 5 to 15 per cent of cases. At this early stage of cancer genetics,
      the risks associated with particular mutations are not known, there are no proven
      and acceptable strategies for women with an inherited susceptibility to
      ameliorate risk or improve prognosis, and risk estimates appropriate for
      Australian women with a family history of breast cancer are not established,
      although data from the United States may overestimate risk. Information is needed
      from population-based studies, such as the Australian Breast Cancer Family Study
      (Hopper et al. Breast 1994; 3: 79-86), but 100 per cent mutation detection in
      large cancer genes is difficult and expensive. Development of a systematic,
      research-oriented, evidence-based approach to genetic testing in Australia is
      recommended. Australia could lead the world in having common protocols used in
      breast cancer clinics across the country, linked to a national research
      consortium and database.

PMID- 8987215
TI  - Needs assessment must become more change-focused.
AB  - Area-based needs-assessment methods tend to reinforce the status quo in service
      or program delivery rather than challenge it. Data collection easily becomes
      routine and self-justifying. To rid ourselves of ritualistic methods of data
      collection, we must turn attention to the process of change that should result
      from it. That is, we must think in advance of the types of decisions that must
      made about service delivery and the nature of the change process itself. There
      are two routes to this end, depending on how change is conceptualised. If one
      adopts a conflict model of change, then felt need or, more crudely, what
      consumers or groups and communities want becomes the primary focus. This would
      place consumers in the chief role within an action-oriented advocacy process.
      Alternatively, if a more functionalist model of change is adopted, then the focus
      of activity is on the information needs of managers and the type of data they
      require to justify a resource shift. Typically these data are not about "needs'
      but marginal health gains and costs. In either event, the data collection
      procedures should be far more specific and directed than the existing broad-brush
      procedures that presently serve only a limited purpose and effectively dilute or
      detract from both agendas for change. There are several possible pathways to
      resolve some of these issues, in particular, using hypothetical results to
      foresee if or how change could result from any proposed data collection activity.

PMID- 8987216
TI  - Nonfatal firearm misuse: licence status of perpetrators and legality of the
      firearms.
AB  - The primary aim of this study was to identify the licence status of those
      involved in incidents of nonfatal firearm-related misuse and to determine the
      involvement of legal firearms in such incidents. Firearm-related attempted
      suicides were excluded. The study also sought to identify the types of firearms
      most likely to be misused. Over a three-month period in early 1994, all nonfatal
      firearm-related incidents reported in any New Zealand newspaper were identified
      by a commercial clipping bureau. Data pertaining to the licence status and the
      legality of the firearm involved in these incidents were obtained from the police
      who completed a standardized questionnaire under the Official Information Act
      (1982). Over the study period, 78 incidents yielded information on 97
      perpetrators and 100 firearms. Of the 97 perpetrators, 66 per cent were
      unlicensed, 20 per cent were licensed, the licence status of 8 per cent of the
      perpetrators was unknown and the remaining 7 per cent were using air guns and
      therefore a licence was not required. Half of the perpetrators involved in
      domestic disputes were licensed. Of the 100 firearms, 44 per cent were classified
      as "legal firearms' and 56 per cent were classified as "illegal firearms'. These
      findings suggest that strategies aimed at reducing or preventing injury due to
      firearm misuse must focus on both licensed and unlicensed individuals and both
      legal and illegal firearms.

PMID- 8987217
TI  - Estimating nonparticipation bias in a longitudinal study of bereavement.
AB  - Nonparticipants in epidemiological studies may differ in important respects from
      participants but the magnitude of this potential bias is rarely quantified. This
      study estimates the effect of nonparticipation on estimates of mental health
      problems following stillbirth, neonatal death or sudden infant death syndrome. Of
      805 families approached, 512 (64 per cent) were recruited, of whom 77 per cent of
      mothers and 71 per cent of fathers completed four study interviews. Younger,
      unmarried, unemployed parents without private health insurance were less often
      recruited, and even if recruited, were less likely to complete the interview. By
      evaluating several possible scenarios, we estimated that had mothers lost to
      follow-up remained in the study, anxiety rates would have varied by no more than
      +/-4 per cent. Relative risks associated with bereaved-control comparisons would
      have differed little from the observed estimate of 2.33. Estimating the effects
      of initial nonresponse is more difficult but the adoption of a worst-case
      scenario produced a relative risk of 3.47. Despite systematic nonparticipation
      suggestive of social disadvantage, attrition-related bias may have had only a
      modest effect on anxiety and depression rate estimates. However, this may not be
      the case when sample loss is high, when associations between attrition and
      outcome are strong, and when attrition-related behaviour differs across
      comparison groups.

PMID- 8987218
TI  - Rodenticide poisoning among children.
AB  - We aimed to determine the nature, extent and sequence of events of accidental
      childhood poisoning with rodenticides and identify potential intervention
      strategies. Subjects were identified prospectively from callers to the Victorian
      Poisons Information Centre and those presenting to the Emergency Departments of
      hospitals participating in the Victorian Injury Surveillance System from 1 April
      to 31 December 1993. The events preceding rodenticide ingestion were examined via
      telephone questionnaire involving 128 parents or guardians of children under five
      years exposed to rodenticides. Rodenticides are not leading agents for severe
      poisoning but are a frequent and increasing cause of less severe poisoning. Most
      children (90 per cent) had obtained the rodenticide from the site at which it had
      been laid, usually by the caregiver (67 per cent), in the kitchen, lounge room or
      laundry, inside cupboards or-wardrobes. In 69 per cent of these cases,
      respondents thought the site would not normally allow access to children. Only 13
      per cent of children were admitted to hospital, although 41 per cent sought
      medical attention. Most caregivers (90 per cent) were aware of some dangers
      associated with rodenticides. Children usually ingest insufficient amounts of
      rodenticide to cause serious effects. However, medical assessment and monitoring
      of prothrombin times is often indicated, with a consequent cost to the healthcare
      system. Potential countermeasures, focusing on packaging and positioning of
      rodenticide baits, product reformulation, and the distribution of management
      guidelines for health workers, were identified. Implementation of the identified
      countermeasures was initiated by a workshop involving stakeholders from industry,
      research and health professions.

PMID- 8987219
TI  - Why? Who? How? Estimating numbers of illicit drug users: lessons from a case
      study from the Australian Capital Territory.
AB  - There is currently a resurgence of interest in estimating numbers of illicit drug
      users in Australia. Defining why numbers are needed, who is to be counted and how
      estimates should be derived are vital steps in the production of useful, valid
      estimates. We present a range of estimates of heroin users in the Australian
      Capital Territory which were developed as part of an investigation of the
      feasibility of prescribing heroin to dependent users. These produced estimates
      ranging from 433 to 1251 users. We conclude that household surveys, capture
      recapture, and multipliers derived from nomination techniques have serious and
      often unrecognised limitations. Capture-recapture estimates, in particular, are
      unlikely to be useful, except at a local level. The best way forward for the
      derivation of national estimates for the National Drug Strategy is a three
      pronged approach; national surveys, validated multipliers and monitoring of key
      indicators by drug-related services and agencies.

PMID- 8987220
TI  - Barriers to health promotion activities in public hospitals.
AB  - Despite the central role hospitals have in the health care system, relatively few
      health promotion activities are conducted in Australian public hospitals. This
      study investigated the types of obstacles that were perceived to inhibit health
      promotion activities in hospitals. A questionnaire for self-completion was sent
      to medical superintendents in all public hospitals in Queensland and 112
      questionnaires were returned (92.6 per cent response rate). The results indicated
      that lack of finance, lack of interest by relevant others, and needs (for
      appropriate programs, training and patient receptivity) were the barriers
      reported by superintendents. The barriers of 'interest' and 'needs' were related
      to a lack of written policies in some areas, but not directly to levels of other
      health promotion activities being conducted in the hospitals. Success in
      facilitating health promotion programs in hospitals will need to include a change
      in the environment, in particular the views of medical superintendents. The
      combination of attitude change and the availability of a motivated person (such
      as a health promotion officer) to lead the activities may be needed in order to
      produce an increase in the level of health promotion in public hospitals.

PMID- 8987221
TI  - Deaths in Broome, Western Australia, 1883 to 1994.
AB  - We examined all records of deaths held in the Derby Courthouse (1883 to 1895) and
      the Broome Courthouse (from 1896). Records of 3409 deaths (2659 males, 750
      females) were analysed. Race of origin was ascertained from > 99 per cent of
      records: 35.9 per cent of deaths were of Aboriginals, 42.8 per cent of Asians and
      21.3 per cent were among other races. In the early decades (1880s to 1920s) most
      deaths were of young Asian males and related to deep-sea diving in the pearling
      industry; many other deaths were caused by homicide and suicide. Pearling deaths
      declined after World War I and the number of Aboriginal deaths increased. The 80
      to 100 deaths caused by the Japanese air raid in March 1942 were not entered into
      the Broome register. After World War II deaths among young males and Asians
      decreased and reported Aboriginal deaths increased; many were of malnourished
      infants and young children with infections. In the 1970s and 1980s deaths of
      young adults in motor vehicle accidents and of young adults from homicide and
      suicide increased; some occurred in custody. The pearling industry caused
      hundreds of deaths in the late nineteenth century and in the first two decades of
      this century, particularly among young Asian divers. Many were recorded in the
      Derby and Broome Death Registries but others were not recorded. These official
      records show changing patterns of mortality, for example, mortality associated
      with violence, infection and undernutrition (in young Aboriginal children), and
      more recently, motor vehicle accidents.

PMID- 8987222
TI  - Healthy and unhealthy life styles of female brothel workers and call girls
      (private sex workers) in Sydney.
AB  - Two groups of female sex workers were compared with respect to their healthy or
      unhealthy life styles. Both 'call girls' (private sex workers) and brothel
      workers were infected with sexually transmitted diseases as often in their
      noncommercial sexual relations as in their work, smoking was a serious problem
      for both, and each group endured problems from clients specific to their work
      sites. However, overall, the call girls had healthier life styles, but were more
      vulnerable to pressures from clients for unsafe sex and to potential violence.

PMID- 8987223
TI  - Reproducibility of data collected by patient interview.
AB  - This study examined the reproducibility of data, not generally considered at risk
      for poor patient recall, obtained on two separate occasions. Our study used data
      collected for a register of heart attacks in the Lower Hunter Region of New South
      Wales, and included 1675 patients who were registered at least twice. Reporting
      inconsistencies between occasions were assessed for eight data items. We found
      that the sex of five patients had been recorded differently on the two occasions.
      Among patients interviewed on both occasions, between 0.5 per cent and 2.0 per
      cent of patients had inconsistent reports for marital status, country of birth,
      smoking status and height, 2.7 per cent for date of birth, 13 per cent for
      education level and between 1.6 per cent and 9.6 per cent for the history of
      various medical conditions. Patients not from an English-speaking background,
      over 60 years of age or without tertiary education tended to have higher rates of
      inconsistent reporting. Time between occasions, marital status and sex were not
      associated with increased rates of inconsistent reporting. We concluded that
      apparently straightforward data items, such as date of birth and education level,
      were not perfectly reproducible when obtained by patient interview on separate
      occasions. Our results provide a starting point for sensitivity analysis in other
      studies if the potential inaccuracies in reporting of such data should be of
      concern.

PMID- 8987224
TI  - BCG vaccination practices in Victoria.
AB  - To determine the patterns of usage of bacille Calmette-Guerin (BCG) vaccine in
      Victoria and assess whether the vaccine was being administered to those in high
      risk groups, as identified by the National Health and Medical Research Council,
      an audit of BCG vaccine unit sales and expenditure, over the past four years was
      conducted. A postal survey covering all registered Victorian BCG vaccinators
      inquired about BCG vaccination practices during 1993. Vaccine sales and
      expenditure had nearly doubled since 1991. The number of registered vaccinators
      had also increased. The survey response rate was 77 per cent, (228 of 295). Half
      of the vaccinators were working in general practice, 11 per cent of vaccinators
      used no set guideline for client selection, 69 per cent vaccinated fewer than 25
      people in 1993, 26 per cent had vaccinated neonates (mainly southeast Asian),
      with few of these vaccinations being carried out in maternity hospitals. Tertiary
      students and ethnic groups were the most commonly vaccinated groups. Only small
      amounts of BCG were being given to people outside risk groups, mainly travellers
      and anxious public. There has been significant increase in numbers of registered
      vaccinators and use of BCG with much wastage. Application of guidelines was
      inconsistent and coverage of high-risk groups varied. Despite some selection for
      vaccination by personal choice, little vaccine appeared to be used in
      nonrecommended groups. Subsequent changes in practice have resulted, including
      publicising and clarifying guidelines, reduction in the number of vaccinators,
      vaccinator upgrading courses, and restructuring of the vaccine ordering system.

PMID- 8987225
TI  - Investigation of notifications of hepatitis C in 1994: the experience of three
      health departments.
AB  - Laboratories must notify health departments of cases of hepatitis C in
      Queensland, the Northern Territory (NT) and the Australian Capital Territory
      (ACT). Our objectives were to estimate the minimum proportion of notified cases
      of hepatitis C that were recent infections and to determine the risk factors for
      infection of the notified cases. We conducted a retrospective investigation of
      all eligible notifications received at the health departments in Queensland, the
      Northern Territory and the Australian Capital Territory. Of the 963 notifications
      about which information was received, 16 per cent were repeat notifications.
      These were excluded from further analysis. In Queensland, 7 per cent, and in both
      NT and ACT, 3 per cent of the notifications were considered to be recent
      infections. The most common risk factor reported for both recent and all other
      hepatitis C cases was a history of injecting drug use, although the proportion of
      cases with that history was different in NT from ACT and Queensland. Cases were
      tested because of screening programs: for drugs and alcohol, in sexually
      transmitted diseases clinics and prison; and because of clinical indications such
      as a risk factor, symptoms, or results of liver function tests. Another common
      reason for testing was a request from a patient. A significant proportion of
      recorded notifications was repeat notifications. Most notifications were of
      patients who had become infected more than 12 months ago and the most common risk
      factor was injecting drug use. There was not a high proportion of cases with
      unknown risk factors.

PMID- 8987227
TI  - Review of the nutrition policy of the Arnhem Land Progress Association.
AB  - The process of implementation and the effect of the nutrition policy of the
      Arnhem Land Progress Association (ALPA) were reviewed three years after
      implementation of the policy in five remote Aboriginal community retail stores in
      May 1990. In 1993, compliance with the policy varied among stores. Recommended
      foods were available regularly in most communities; however, promotional and
      educational components of the policy were not widely implemented. Dietary
      improvements were evident in those communities where stores most complied with
      the policy. Some aspects of the ALPA nutrition policy require modification, and
      renewed commitment to the policy is likely to improve further the diet in the
      Aboriginal communities involved. The ALPA nutrition policy is a potential model
      for the development of other local food and nutrition policies in remote
      Aboriginal communities.

PMID- 8987226
TI  - Knowledge of cancer risk reduction practices in rural towns of New South Wales.
AB  - The Australian Cancer Society has published guidelines for recommended risk
      reduction strategies for breast, cervical, smoking-related and skin cancer. While
      knowledge may not be sufficient for change, it is argued to be necessary for
      change to occur. A measure of the level of health knowledge in the community can
      be useful for health promotion practitioners, identifying where health messages
      are not reaching their proposed targets. Our aims were to examine the level of
      knowledge about risk reduction practices for breast, cervical, smoking-related
      and skin cancers, for a rural New South Wales sample, and to examine sex and age
      effects on knowledge levels. A survey of 2846 women and 1732 men from rural New
      South Wales, which used an unprompted recall strategy, revealed some notable
      deficits in recall of cancer risk reduction practices: only 26 per cent of women
      identified mammograms as a risk reduction strategy for breast cancer; only 5 per
      cent of women knew at which ages mammograms should start and stop; only 6 per
      cent of women could identify when Pap tests should be discontinued; less than
      half of the sample could identify common solar protection strategies; and less
      than one-third of people identified passive smoking as a lung cancer risk.

PMID- 8987228
TI  - Field epidemiology of an outbreak of dengue fever in Charters Towers, Queensland:
      are insect screens protective?
AB  - Between March and July 1993 a dengue virus epidemic swept through Charters
      Towers, a rural North Queensland mining community of 10,000. This clearly
      delineated outbreak provided an ideal opportunity to carry out one of the few
      field epidemiological studies of dengue in Australia. The epicurve was consistent
      with that of a point source outbreak, 18 weeks in duration and peaking at four
      weeks. A basic reproduction number for the dengue epidemic of 1.99 indicates a
      similar rate of spread to that found in dengue epidemics overseas. A female-to
      male sex ratio of 1.7:1 was obtained for the 238 cases identified. An age- and
      sex-matched retrospective case-control study showed that cases were significantly
      more likely to live in unscreened houses than were controls (McNemar chi 2 = 56.1
      df, P < 0.0001). Despite being generally accepted, an association between insect
      screens and a reduced incidence of mosquito-borne diseases has not previously
      been demonstrated in Australia. We speculate that unscreened housing facilitates
      the initial spread of a dengue epidemic.

PMID- 8987229
TI  - Drowning fatalities of children in Tasmania: differences from national data.
AB  - All drownings of people under 15 years of age in Tasmania from 1981 to 1993 were
      identified from the Tasmanian coroner's case files. Age- and sex-specific
      mortality rates were calculated and found to be similar to Australian drowning
      mortality rates. An exception was the lower drowning rate for Tasmanian females
      aged 0 to 4 years. Only 9 per cent of drowning deaths were caused by immersion in
      a swimming pool, 32 per cent of deaths occurred in dams and ponds and 21 per cent
      occurred in a river. Most drownings (88 per cent) associated with dams, ponds,
      swimming pools and baths were in the 0-to-4-year age group. Compared with
      Australia as a whole, toddlers drowning in swimming pools is uncommon in
      Tasmania; however, there are relatively more drownings in dams and ponds.
      Strategies for the prevention of drowning in childhood in Tasmania should
      consider the hazards associated with rural living.

PMID- 8987230
TI  - Prevalence of tuberculosis infection among primary school-entry children in
      Sydney.

PMID- 8987231
TI  - Entering the "land of the "puter braindead"!
AB  - My goal has been to give you a basic understanding of the concepts involved with
      understanding and exploring the web. By this point you should know: what the
      Internet is, what the World Wide Web is, what a web site is, what a home page is,
      what a URL is, what a browser is, what hyperlinks are, and how to use your
      browser to surf the web. Problems that arise can usually be solved by going to
      the "Help" icon on your browser or going to the Web Tutorials that all browsers
      have on their software.

PMID- 8987232
TI  - The Internet and medical education.
AB  - The Internet is a watershed event. Access to information resources throughout the
      world has never been greater or easier. The Internet's effect on medicine,
      education and practice, is being expanded and redefined daily. Understanding what
      the Internet is and how it is effecting medical education and medical practice
      will be vital to the successful practitioner. This paper will provide historical
      information on the development of the Internet and define the current terminology
      used by computer professionals and the media. It will discuss how the Internet is
      currently being used and why you want to be a part of it.

PMID- 8987233
TI  - Medical resources on the World Wide Web (WWW).

PMID- 8987234
TI  - Drug-related blood dyscrasias. Introduction.

PMID- 8987235
TI  - When should the clinician suspect a drug-induced blood dyscrasia, and how should
      he proceed?
AB  - Blood dyscrasias account for only a minor fraction of all adverse drug reactions
      (ADRs), but are relevant because of their relatively high morbidity and
      mortality. For the majority of drugs, the magnitude of risk is low enough to
      remain undetected until wider distribution of the drug takes place. Thus, only
      post-marketing studies, carried out with appropriate methodology and sufficient
      statistical power, will allow the risk of serious haematological side-effects of
      new drugs to be ascertained. Publication of carefully studied and thoroughly
      described single case studies and reports to registries are necessary to detect
      new associations between drugs and blood dyscrasias, while only large cohort or
      case-control studies are suited to quantify the risks. Physicians managing a
      newly detected blood dyscrasia should be aware that it may be drug-induced. They
      should assess the exact diagnosis, obtain and thoroughly document a detailed
      exposure history and follow the blood counts after withdrawal of all potentially
      relevant agents. The recognition and appropriate management of the problem in
      individual cases is the basis for both effective patient care and the quality of
      subsequent pharmaco-epidemiological evaluation.

PMID- 8987236
TI  - Aetiology of severe aplastic anaemia and outcome after allogeneic bone marrow
      transplantation or immunosuppression therapy. Working Party on Severe Aplastic
      Anaemia of the European Blood and Marrow Transplantation Group.
AB  - This study is based on 2163 patients with severe aplastic anaemia from the
      European Bone Marrow Transplantation Working Party Registry on Severe Aplastic
      Anaemia. It was designed to define patients' characteristics according to
      different aetiology and to assess the impact of aetiology of the aplasia on
      treatment outcome. Significant differences were found in age, sex, disease
      severity and DR typing between idiopathic, post-hepatitis and drug-associated
      severe aplastic anaemia. These differences did not affect the overall outcome of
      patients treated with bone marrow transplantation (BMT) or immunosuppression (IS)
      therapy.

PMID- 8987237
TI  - Drugs in the aetiology of agranulocytosis and aplastic anaemia.
AB  - Agranulocytosis and aplastic anaemia are rare but serious conditions known to be
      caused by numerous drugs. Most of what is known or suspected about the aetiology
      is based on case reports, with only a few formal epidemiological studies that
      provide quantitative estimates of risk. Updated results have been obtained from a
      combined analysis of data from 3 case-control studies that used similar methods:
      the International Agranulocytosis and Aplastic Anemia Study (IAAAS), conducted in
      Israel and Europe; a study conducted in the northeast US; and a study conducted
      in Thailand. Totals of 362 cases of agranulocytosis, 454 cases of aplastic
      anaemia and 6458 controls were included in the analyses. The IAAAS and Thai study
      were population-based, providing estimates of the incidence of the 2 dyscrasias.
      The overall annual incidence of agranulocytosis in the ambulatory population was
      3.4/10(6) in the IAAAS and 0.8/10(6) in Thailand; by contrast the incidence of
      aplastic anaemia was 2.0/10(6) in the IAAAS and 4.1/10(6) in Thailand. A total of
      21 compounds were significantly associated with an increased risk of
      agranulocytosis in the IAAAS and US studies. Excess risks ranged from 0.06 to 13
      cases/10(6) users/wk; the most strongly associated drugs were procainamide, anti
      thyroid drugs and sulphasalazine. An association with drugs that had previously
      been suspected was also seen in Thailand. The overall aetiologic fractions of
      agranulocytosis due to drug use were 62% in the IAAAS, 72% in the US and 70% in
      Thailand. Eleven drugs were significantly associated with an increased risk of
      aplastic anaemia, with excess risks ranging from 1.4 to 60 cases/10(6) users in a
      5-month period. The most strongly associated drugs were penicillamine, gold and
      carbamazepine. Aetiologic fractions were 27% in the IAAAS, 17% in the US and 2%
      in Thailand, which paralleled the prevalence of use of associated drugs in the 3
      populations. The present results confirm that agranulocytosis is largely a drug
      induced disease, with similar proportions accounted for in 3 disparate geographic
      regions. By contrast, although many of the expected associations were observed
      for aplastic anaemia, most of the aetiology is not explained by drugs. For all
      associated drugs, the excess risks are sufficiently low that blood dyscrasias
      should not figure prominently in the balancing of risks and benefits.

PMID- 8987238
TI  - Incidence and non-drug aetiologies of aplastic anaemia in Thailand. The Thai
      Aplastic Anaemia Study Group.
AB  - A population-based, case-control study of aplastic anaemia has been conducted in
      Thailand since 1989. Up to December 1994, the overall annual incidence was
      3.9/10(6) in Bangkok, 5.0/10(6) in Khonkaen and 3.0/10(6) in Songkla. In Bangkok,
      the incidence peaked in 2 age groups (at 15-24 yr and > or = 60 yr), whereas in
      Khonkaen and Songkla there was a consistent increase in incidence with increasing
      age. The results of case-control analyses for non-drug risk factors indicate a
      strong inverse association with socio-economic status present in all 3 areas; a
      strong association with grain farming in the 2 rural areas that does not appear
      to be explained by pesticides; an association with occupational exposure to
      solvents in Bangkok; and a positive association with hepatitis A seropositivity.

PMID- 8987239
TI  - Drug use and aplastic anaemia: the French experience. French Cooperative Group
      for the Epidemiological Study of Aplastic Anaemia.
AB  - The cause of the rare and severe condition of aplastic anaemia is largely
      unknown, although certain drugs have been implicated as possible aetiological
      factors, mostly through the evidence of case reports. A case-control study was
      conducted in metropolitan France between 1985 and 1988 to investigate
      aetiological factors in aplastic anaemia. It was conducted in parallel with the
      establishment of a national register of the incidence of aplastic anaemia, which
      started in May 1984. The controls used in the study consisted of 2 hospitalized
      controls (i.e. patients admitted to hospital at the same time as the case) and a
      neighbour control named by the case. All three controls were matched for age and
      sex, and were interviewed by the same investigator as the case. A total of 147
      cases, 287 hospitalized controls and 108 neighbour controls were interviewed. An
      association of varying degrees was noted between aplastic anaemia and the
      following conditions or treatments: clinical hepatitis during the past 6 months;
      history of chronic immune disorder (mainly rheumatoid arthritis); gold salts and
      D-penicillamine; colchicine and allo-thiopurinol; acetaminophen and salicylates.
      This survey confirmed the vanishing role of previously known toxic agents in the
      aetiology of aplastic anaemia. Some differences observed between the results of
      the present study and those published previously suggest that targeted studies on
      each category of drug according to specific disease areas should be initiated.

PMID- 8987240
TI  - Drug-related blood dyscrasias in a Swedish reporting system, 1985-1994.
AB  - Drug-related blood dyscrasias as reported in Sweden during a 10-yr period have
      been analysed in relation to sales and prescription data. The number of cases
      reported were as follows: agranulocytosis 390, thrombocytopenia 391, pancytopenia
      50 and aplastic anaemia 36. The annual incidence rates per 10(6) inhabitants
      were: agranulocytosis 4.8, thrombocytopenia 5.6, pancytopenia 1.1 and aplastic
      anaemia 0.5. Incidences in the elderly were higher for all dyscrasias except
      aplastic anaemia. The most commonly reported drugs for all dyscrasias were
      sulphonamides and diuretics, but when related to sales data the risk of
      agranulocytosis was high for clozapine, dapsone, mianserin and sulphasalazine,
      while the risk did not seem to be increased for furosemide. For thrombocytopenia,
      furosemide, co-trimoxazole and the measles, mumps and rubella vaccine were most
      commonly reported. The risk for pancytopenia and aplastic anaemia was increased
      for acetazolamide and co-trimoxazole. As spontaneous reporting systems are
      primarily set up for signalling purposes, such data must always be interpreted
      with utmost care.

PMID- 8987241
TI  - An epidemiological study of aplastic anaemia: relationship of drug exposures to
      clinical features and outcome.
AB  - Two hypotheses were examined in the combined data from 3 case-control studies of
      aplastic anaemia, conducted in Thailand, Europe/Israel and the US: 1. Cases
      exposed to drugs associated with a significantly increased risk of aplastic
      anaemia are more likely to present with thrombocytopenia (e.g. petechiae, easy
      bruising); and 2. cases exposed to these drugs are more likely to recover quickly
      than non-exposed cases. After excluding all cases who lacked information on
      timing of symptoms and those whose symptoms began > or = 180 d before hospital
      admission, 392 cases remained for analysis. A total of 51 (13%) had been exposed
      to one of the significantly associated drugs; the remaining 341 (87%) had not.
      Among the former, 31% reported thrombocytopenia either before or at the same time
      as non-bleeding symptoms (e.g. pallor, fatigue); the corresponding proportion
      among the non-exposed was 53%. Data on time to recovery (return of the 3 blood
      cell lines to normal levels) were not available for the Thai cases; among the
      others, the median time to recovery for the non-fatal cases was 7 and 6 months in
      the 29 exposed and the 83 non-exposed cases, respectively. The data do not
      support either hypothesis: the two groups of aplastic anaemia cases appeared to
      be similar in both the presenting symptoms and the recovery time.

PMID- 8987242
TI  - Immune pathophysiology of acquired aplastic anaemia.
AB  - Clinical observations and laboratory studies have supported an immune basis for
      most acquired aplastic anaemias, with the majority of patients responding to
      immunosuppressive therapy. In vitro, interferon (IFN) and tumour necrosis factor
      (TNF) inhibit haematopoiesis, including colony formation by early and late
      progenitor cells and the generation of long-term culture initiating cells
      (LTCIC). These lymphokines induce Fas antigen expression on CD34+ cells and
      apoptosis within the haematopoietic cell compartment. Local secretion of
      cytokines is far more potent than addition to long-term bone marrow cultures.
      Activated cytotoxic lymphocytes, high levels of INF gamma and TNF alpha, and
      increased Fas expression on CD34+ marrow cells are present in patients.
      Haematopoiesis is severely diminished in severe aplastic anaemia on presentation:
      CD34+ cell numbers, colony forming cells and LTCIC are all markedly decreased.
      LTCIC numbers do not predict recovery. Blood cell counts increase in some cases
      in the absence of changed numbers of LTCIC, but recovered patients have higher
      and sometimes normal LTCIC numbers. The mechanism by which chemical and
      biological agents incite altered immunity remains unclear. Drug associations have
      been inferred from case reports and formal epidemiological studies, but have
      remained refractory to systematic laboratory study. Whatever the initial events,
      immune system destruction of haematopoiesis plays a central role in the
      development of acquired aplastic anaemia.

PMID- 8987243
TI  - Could aplastic anaemia be considered a pre-pre-leukaemic disorder?
AB  - Clinical evidence for a link between aplastic anaemia, paroxysmal nocturnal
      haemoglobinuria (PNH) and hypoplastic leukaemia is provided by studies of clonal
      disorders, which may be a complication of congenital or acquired aplastic
      anaemia. Fanconi's anaemia is the most common congenital disorder and leukaemia
      occurs in at least 10% of cases. In acquired aplastic anaemia, a high incidence
      of myelodysplastic syndrome (MDS) was noted in patients with aplastic anaemia,
      seemingly cured of their aplasia by antilymphocyte globulins (ALG). In a recent
      survey, the 10-year cumulative incidence rates were 9.6% for MDS, 6.6% for acute
      leukaemia (115-fold higher than in the general population). Biological evidence
      is provided by bone marrow morphology, as a certain degree of dysmyelopoiesis is
      not unusual in aplastic anaemia. Cytogenetic analyses in aplastic anaemia are
      scarce, but data have shown clonal cytogenetic abnormalities at diagnosis in
      otherwise typical aplastic anaemia. Recently, flow cytometry to assess the
      glycosyl-phosphatidylinositol (GPI) molecule defect in PNH has demonstrated that
      a significant proportion of patients with otherwise typical aplastic anaemia
      have, in fact, a GPI defect due to alterations within the PIG-A gene. Finally,
      aplastic anaemia patients were recently reported to have molecular evidence of
      clonal haematopoiesis; this must now be discussed in light of recent clonality
      studies in normal individuals. The clinical and biological evidence for a link
      between aplastic anaemia, PNH and hypoplastic leukaemia allows the generation of
      a model of aplastic anaemia as a possible pre-pre-leukaemic disorder.

PMID- 8987244
TI  - Immune mechanisms leading to drug-induced blood dyscrasias.
AB  - Drug-induced blood dyscrasias may be due to toxicity of the drug, inborn errors
      of metabolism or immunological reactions. In the latter case, drug-induced
      antibodies are directed to specific target cells, such as platelets
      (thrombocytopenia) or granulocytes (agranulocytosis). Some of these immune
      mechanisms are based on the physical interaction between drug, antibody and
      target cells. A particular drug may bind to the surface of the blood cell which,
      as a carrier of the drug, will be destroyed as part of the immune reaction to the
      drug (hapten mechanism). Other drugs will form immune complexes with drug
      specific antibodies. These immune complexes will bind to certain blood cells and
      destroy them as innocent bystanders (immune complex mechanism). In vitro assays
      are described which enable the offending drug to be detected by mimicking these
      immune mechanisms using patient serum, platelets or granulocytes, and the
      suspected drug. The diagnostic value of these in vitro assays is discussed.

PMID- 8987246
TI  - Long-term bone marrow cultures in aplastic anaemia.
AB  - The long-term bone marrow culture (LTBMC) system provides an in vitro
      physiological model for the study of stromal cell mediated haemopoiesis in
      patients with aplastic anaemia. The two aspects of haemopoiesis--stromal and stem
      cell function--can be analysed separately using a modification of LTBMC with
      cross-over studies. Patients with aplastic anaemia universally demonstrate
      defective stem cell function in terms of reduced or absent marrow repopulating
      ability, reflecting a deficiency of long-term culture initiating cells. Defects
      in stromal cell function, as assessed by the ability of aplastic anaemia stroma
      to support normal generation of haemopoietic progenitors, are not common, but may
      conceal an isolated deficiency of a particular growth factor in some patients due
      to the overlapping nature of haemopoietic growth factor activities. The stem cell
      abnormality in aplastic anaemia reflects a deficiency in cell numbers, as well as
      dysfunction in certain cases. An increased level of apoptosis in aplastic anaemia
      marrow CD34+ cells exists, and this correlates well with disease severity. LTBMC
      studies demonstrate that more of the haemopoietic cells are nonviable (apoptotic
      and dead) compared with normal controls, and this correlates with reduced colony
      (CFU-GM) generation. An increase in apoptosis among primitive haemopoietic cells
      may contribute to the stem cell defect in aplastic anaemia. Haemopoietic growth
      factors such as G-CSF, when given after immunosuppressive therapy such as
      antilymphocyte globulin and cyclosporin for aplastic anaemia, may act partly by
      reducing the increased level of apoptosis, resulting in improved stem cell
      survival.

PMID- 8987245
TI  - The role of cytokines in haematopoiesis.
AB  - Cytokines, by definition, exert an effect on haematopoiesis. Diseases
      characterized by haematopoietic insufficiency, such as aplastic anaemia, should
      therefore be investigated for abnormal expression of these regulatory proteins.
      In studies on hairy cell leukaemia, a severe deficiency was found in the
      production of interleukin-3 (IL-3), granulocyte-macrophage colony stimulating
      factor (GM-CSF), granulocyte CSF, IL-6 and tumour necrosis factor alpha (TNF
      alpha). Further studies on IL-6 at the mRNA and protein levels revealed that
      peripheral blood mononuclear cells and even hairy cells could be stimulated by
      interferon alpha (IFN alpha) to produce IL-6. It is interesting to speculate on
      the beneficial effects of IFN alpha therapy on the expansion of normal
      haematopoiesis and suppression or even elimination of malignant cells. Studies on
      a patient with angio-immunoblastic lymphadenopathy, another disease showing
      haematopoietic insufficiency, who developed severe aplastic anaemia, showed
      massive increases in IFN gamma and TNF alpha levels in serum; IL-6 and GM-CSF
      levels were below the limit of detection. These results correlated with an
      abnormal distribution of CD4+ and CD8+ T lymphocytes in the patient's blood and
      were compatible with the suppressive effects of IFN gamma and TNF alpha on
      haematopoiesis.

PMID- 8987247
TI  - Reactive metabolites and agranulocytosis.
AB  - Central to most hypotheses of the mechanism of idiosyncratic drug-induced blood
      dyscrasias is the involvement of reactive metabolites. In view of the reactive
      nature of the majority of such metabolites, it is likely that they are formed by,
      or in close proximity to the blood cells affected. The major oxidative system of
      neutrophils generates hypochlorous acid. We have demonstrated that the drugs
      associated with the highest incidence of agranulocytosis are oxidized to reactive
      metabolites by hypochlorous acid and/or activated neutrophils. There are many
      mechanisms by which such reactive metabolites could induce agranulocytosis. In
      the case of aminopyrine-induced agranulocytosis, most cases appear to involve
      drug-dependent anti-neutrophil antibodies, and these are likely to be induced by
      cell membrane antigens modified by the reactive metabolite of aminopyrine. The
      target of agranulocytosis associated with many other drugs is usually neutrophil
      precursors and may involve cytotoxicity or a cell-mediated immune reaction
      induced by a reactive metabolite. In the case of aplastic anaemia, there is
      evidence in some cases for involvement of cytotoxic T cells, which could either
      be induced by metabolites generated by neutrophils, or more likely, by reactive
      metabolites generated by stem cells.

PMID- 8987248
TI  - Anti-cytochrome P450 autoantibodies in drug-induced disease.
AB  - Drugs may induce hepatitis through immune mechanisms. In this review we have used
      the examples of 2 drugs to elucidate the first steps leading to the triggering of
      such disease, namely tienilic acid (TA) and dihydralazine (DH). These drugs are
      transformed into reactive metabolite(s) by cytochrome P450 (2C9 for TA and 1A2
      for DH) (step 1). The reactive metabolites produced are very short-lived and bind
      directly to the enzymes which generated them (step 2). A neoantigen is thus
      formed which triggers an immune response (step 3), characterized by the presence
      of autoantibodies in the patient's serum (step 4). The autoantibodies are
      directed against the cytochrome P450 which generated the metabolite(s). Although
      the process by which TA and DH induce-hepatitis has been elucidated, further
      studies are necessary to generalize this mechanism. In addition, an animal model
      will also be useful to fully understand the immune mechanism of this type of
      disease.

PMID- 8987249
TI  - Pharmacogenetics and blood dyscrasias.
AB  - Pharmacogenetic differences in the handling of and response to drugs can markedly
      alter the risk of severe idiosyncratic adverse drug reactions, including
      neutropenia, agranulocytosis and aplastic anaemia. Inherited deficiencies of drug
      metabolizing enzymes can shunt the metabolism of drugs to metabolites which are
      directly toxic (e.g. 6-mercaptopurine metabolism to 6-thioguanine nucleotides) or
      towards electrophilic metabolites which can kill cells and/or lead to a host
      immune response (e.g. sulphonamide metabolism to hydroxylamine metabolites).
      Defects in detoxification pathways (e.g. glutathione conjugation) similarly can
      predispose patients to adverse outcomes. The advent of molecular screening tools
      to define individual (rather than population) risk may lead to the use of
      clinical laboratory tests to identify/predict idiosyncratic adverse drug
      reactions.

PMID- 8987250
TI  - Mechanisms, chemical structures and drug metabolism.
AB  - From the studies that have been done by many laboratories over the last 2
      decades, it is now clear that the toxicities produced by many drugs are due to
      their reactive metabolites. It is though that, in many cases, reactive
      metabolites cause toxicity by binding covalently to tissue proteins. However,
      until recently it was difficult to identify these protein targets. Due to the
      development of an immunochemical approach, this problem has been overcome, as is
      illustrated here by studies that have been conducted on the metabolic basis of
      the idiosyncratic hepatitis caused by the inhalation anaesthetic halothane. The
      major problem to solve in the future will be to determine how protein adduct
      formation leads to toxicity. It is possible that protein adduct formation may
      alter an important cellular function or may lead to immunopathology, as is
      thought to occur in the case of halothane hepatitis. If an allergic reaction is
      suspected, purified protein targets of reactive metabolites can serve as antigens
      for identifying sensitized individuals. This information can be used to prevent
      not only an allergic reaction to the drug, but possible cross-reactions to other
      drugs that are structurally related. Another important application of these
      studies is the design of safer alternative drugs that will not produce
      structurally similar toxic reactive metabolites.

PMID- 8987251
TI  - Overview of benzene-induced aplastic anaemia.
AB  - The scientific literature is replete with reports of cases of benzene-induced
      toxicity to the haematopoietic system. These mainly involve aplastic anaemia, the
      first cases of which were reported in 1897. At high level of benzene exposure
      (air concentration > 100 p.p.m.), the incidence of aplastic anaemia is
      approximately 1/100 individuals exposed, but this drops precipitously at lower
      levels of exposure (10-20 p.p.m.) to around 1/10,000. Factors that affect
      susceptibility may include high liver cytochrome P450 2E1 activity and low folic
      acid intake. The mechanism of benzene-induced aplastic anaemia remains unclear,
      but is likely to involve: (a) metabolism of benzene in the liver; (b) transport
      of metabolites to the marrow and their secondary activation to toxic quinones and
      free radicals by peroxidase enzymes; (c) induction of apoptosis, DNA damage and
      altered differentiation in early progenitor cells; and (d) depletion of the stem
      cell pool.

PMID- 8987252
TI  - Metabolic basis of benzene toxicity.
AB  - Potential metabolic mechanisms underlying the haemopoietic toxicity of benzene
      include bioactivation of phenolic metabolites of benzene by peroxidases in bone
      marrow and ring opening reactions to generate muconate derivatives. Peroxidase
      mediated activation of phenolic metabolites of benzene generates reactive
      quinones which can be detoxified by NAD(P)H:quinone acceptor oxidoreductase
      (NQO1). The major peroxidase enzyme in bone marrow is myeloperoxidase (MPO) and
      potential target cells for phenolic metabolites of benzene were characterized in
      bone marrow stroma on the basis of high MPO:NQO1 ratios. MPO was found to be
      expressed at the level of myeloid progenitor cells in both murine (lineage
      negative cells) and human (CD34+ cells) systems. This suggests that progenitor
      cells may be relevant targets of phenolic metabolites of benzene resulting in
      aberrant haemopoiesis. A polymorphism in NQO1 is also described which leads to a
      complete lack of NQO1 activity. The toxicological significance of this
      polymorphism with respect to benzene toxicity is under investigation.

PMID- 8987253
TI  - The effects of benzene and other leukaemogenic agents on haematopoietic stem and
      progenitor cell differentiation.
AB  - A characteristic shared by a diverse group of myelotoxic compounds and
      leukaemogens is the ability to act synergistically with granulocyte-macrophage
      colony stimulating factor (GM-CSF) in increasing clonogenic response.
      Pretreatment of murine or human bone marrow cells with the benzene metabolite,
      hydroquinone, but not phenol, catechol or trans, trans-muconaldehyde, results in
      a selective enhancement of GM-CSF but not an interleukin-3 (IL-3)-mediated
      clonogenic response. Clonal enhancement is preserved and magnified in enriched
      populations of CD34+ cells (> 95% purity), suggesting an intrinsic effect on
      haematopoietic progenitor cell (HPC) recruitment rather than a secondary effect
      involving accessory cytokines. Clonogenic enhancement of murine HPCs is not
      accompanied by alterations in GM-CSF receptor expression or ligand affinity and
      appears to be mediated via a p53-independent mechanism. These observations
      suggest that hydroquinone treatment alters recruitment and differentiation in a
      primitive subpopulation of CD34+ cells and are consistent with a role for altered
      stem cell differentiation in the development of chemically induced
      myelodysplasias.

PMID- 8987255
TI  - Mechanisms.

PMID- 8987254
TI  - Epidemiology.

PMID- 8987256
TI  - Blood dyscrasias and the pharmaceutical industry: screening surveillance and
      monitoring, and future drug development.

PMID- 8987257
TI  - Thoughts of euthanasia.

PMID- 8987258
TI  - Hawaii needs a policy on assisted suicide.

PMID- 8987259
TI  - Multidisciplinary evaluation of preschool children in a military psychiatry
      clinic: a 10-year comparison and a brief outcome study.
AB  - A little over a decade ago, the Child and Adolescent Psychiatry Service at
      Tripler Army Medical Center opened the Child Study Group (CSG), a
      multidisciplinary diagnostic team clinic for preschool children. The methods and
      results of the clinic were reported previously (Lee, 1987). The current study is
      a comparison of the cohort of children seen from January through December 1984
      with the parallel group seen from January through June 1994. The paper also
      presents a brief follow-up study of the children seen in 1994.

PMID- 8987260
TI  - Origin of the Doppler ultrasound spectrum from blood.
AB  - Backscattering of an incident ultrasound beam by blood gives rise to a Doppler
      spectrum whose characteristics are affected not only by the velocity
      distribution, but also by certain basic aspects of the RBC's behavior. Starting
      from fundamental assumptions, an explicit expression is derived for the Doppler
      spectrum in terms of the variance in the scatterer number density and the
      backscattering cross section. This shows that the Doppler power at a given
      frequency is weighted by the backscattering cross section and the manner in which
      the red blood cells (RBC's) are packed (packing factor). Since spatial variations
      in the flow field can result in changes in the variance and backscattering cross
      section, the mean Doppler frequency will not necessarily be proportional to the
      mean flow through the sample volume. Experimental results for two different flow
      fields are used to illustrate these effects. The implications of these findings
      are discussed in relation to volumetric flow estimation and the power mode
      display used in some color Doppler flow imaging systems.

PMID- 8987261
TI  - Sizing emboli in blood using pulse Doppler ultrasound--I: Verification of the EBR
      model.
AB  - An experiment to verify a theory describing ultrasound backscattering from emboli
      in flowing blood is presented. The theoretical predictions for the backscattered
      power versus embolus size are based on the measurement of the embolus to blood
      ratio (EBR) of backscattered acoustic power. This tool is necessary for in vivo
      clinical application because it removes the need to characterize attenuation and
      reflection loss in heterogeneous tissue. The experiment presented utilizes a
      customized ultrasound pulse Doppler that is capable of interrogating a sample
      volume with two different frequencies concurrently. A flow circuit including a
      3.6-mm-diameter conduit in polyacrylamide gel in which emboli are observed with
      the dual frequency Doppler is described. The flow within the circuit has acoustic
      backscatter coefficient similar to blood due to a calibrated concentration of
      31.1-mu diameter polystyrene microspheres. Polystyrene microsphere "emboli"
      having nominal diameters of 161 and 239 mu are placed in this flow loop and time
      series Doppler shift signatures are recorded. These signatures are investigated
      and a refraction artifact hypothesis is proposed to explain systematic deviation
      of the signatures away from theoretically expected results. Results show that
      gross discrimination of embolus size is feasible.

PMID- 8987262
TI  - Sizing emboli in blood using pulse Doppler ultrasound--II: Effects of beam
      refraction.
AB  - A theoretical and numerical study of the acoustic field intensity within a curved
      flow conduit having 1) diameter similar to the wavelength of the interrogating
      frequency and 2) speed of sound mismatch with the surrounding medium is
      presented. The field intensity is shown to vary significantly and in a monotonic
      fashion across the flow conduit. The resulting insonation of emboli transiting
      through the Doppler sample volume is explored with a Monte Carlo study of the
      behavior of the embolus to blood power ratio (EBR). The numerical simulation
      findings are shown to be in good agreement with previously reported experimental
      results. A method is explored for estimating embolus diameter when this
      refraction artifact is present, and shown to yield excellent results when applied
      to experimental data. Further work toward clinical application of these results
      is discussed.

PMID- 8987263
TI  - Measurement of volumetric flow with no angle correction using multiplanar pulsed
      Doppler ultrasound.
AB  - In this paper we show that by scanning at points on the surface of a sphere that
      the normal angle correction used in pulsed Doppler flow measurements is no longer
      necessary. Thus, it is possible to measure three-dimensional (3-D) flow using
      multiplanar ultrasound even though we only get one-dimensional (1-D) velocity
      information from pulsed Doppler ultrasound. The technique handles the three basic
      problems in flow measurements using ultrasound Doppler: The variations of the
      cross-sectional area, the time dependent changes in the velocity field, and the
      dependency of the angle of insonation. The technique is tested in a flow phantom
      using different angles of insonation to validate the angle independence of this
      new technique. Using six different angles of insonation in the range 0 degree to
      69 degrees with flowrates in the range of 0-170 ml/s a linear dependence was
      found to be: measured (color Doppler) = 0.98 real flow (reference) + 1.36 ml/s,
      with a 95% confidence interval of +/- 13.9 ml/s.

PMID- 8987264
TI  - The design of an optical fiber pressure transducer for use in the upper airways.
AB  - The development of an optical fiber transducer for use in biomedical applications
      has been presented. The design was targeted for use in the upper airways of
      patients with sleep disorders stemming from partial or total occlusion of the
      airway. The transducer's preliminary specification was suited for that of upper
      airway manometry: a resolution of 10 Pa over the range +/- 5 kPa, a single
      transducer being less than 0.94 mm in diameter. Amplitude modulated optical fiber
      sensors are susceptible to loss due to bending of the fiber core and cladding.
      The design of the transducer uses a series of three optical fibers, one emitting
      and two receiving, the combination of the two receiving optical fibers is used to
      reduce effects of light loss: a bend radius of 50 mm is typical for the insertion
      into the naso-pharynx. The transducer transduction element is a silicone gel
      coated with reflective titanium dioxide, the meniscus deforms under pressure and
      modulates the intensity of light reflected back into the receiving optical
      fibers. The main disadvantage of optical fiber pressure transducers is their
      susceptibility to temperature drift. Temperature in the airway rarely changes
      more than 17 degrees C. The frequency of breathing and the high thermal mass of
      the catheter means that temperature drift in this application is not significant,
      and will cause an insignificant error of 12 Pa. The transducer is inexpensive to
      produce, and may be deemed disposable: approximately $20 in material costs (using
      current manufacturing techniques this can be halved). The system has the added
      advantage of being electrically, magnetically, and chemically passive. The
      potential for miniaturization is limited only by the mechanical strength of the
      optical fibers as mechanical problems associated with fragile elastic membranes
      do not apply.

PMID- 8987265
TI  - Deconvolved electrical impedance spectra track distinct cell morphology changes.
AB  - A two-component Cole-Cole model was used to obtain statistically significant fits
      to 100-Hz-10-MHz impedance data for EMT-6 mouse tumors during the progressive
      histological changes induced by hyperthermia. The resulting fitting parameters
      were used to deconvolute and reconstruct the two dispersions which confer the
      predominant impedance features to this tissue. The time-dependent changes of
      these two dispersions were correlated with the concurrent, heat-induced
      morphological changes of the tumors' cells. The higher frequency dispersion (fc
      approximately 1 MHz) was identified with a Maxwell-Wagner relaxation process
      linked to the overall volume response of the cells. The lower frequency
      dispersion (fc approximately 10 kHz) represented an alpha-relaxation associated
      with the surface morphology and integrity of the plasma membranes. Thus, two
      aspects of the characteristic cellular damage sequence in these tumors were found
      to be separately discernable and trackable in real-time using the impedance data.

PMID- 8987266
TI  - Three-dimensional mapping of acute ischemic regions using artificial neural
      networks and tagged MRI.
AB  - Many methods for mapping ischemic myocardial regions by functional analysis have
      been suggested. However, the complicated relationship between myocardial function
      and perfusion, and the inherent limitations of the imaging techniques used, have
      led to a generally low mapping accuracy. We show herein, that highly accurate
      mapping can be obtained by combining tagged magnetic resonance imaging (MRI),
      three-dimensional (3-D) analysis, and artificial neural networks. Nine canine
      hearts with acute ischemia were studied using multiplanar tagged MRI. Twenty-four
      myocardial cuboids were tagged in each heart and reconstructed in 3-D at end
      diastole (ED) and end systole (ES). The cuboids were arranged in three slices
      approximately 1 cm thick and covered most of the left ventricle (LV). Transmural
      thickening and endocardial area strain were calculated for each cuboid. Applying
      a post-mortem (PM) analysis, the percent ischemia in each cuboid was estimated
      using monastral blue dye; the PM analysis served as a "gold standard." An
      artificial neural network (ANN), designed to estimate the percent ischemia in
      each cuboid from the functional indexes, was then created. The ANN "learned" the
      function-ischemia relationship in 192 cuboids taken from eight of the hearts and
      was asked to estimate the percent ischemia in the 24 cuboids of the ninth heart.
      The process was repeated nine times, each time using a different heart as test
      case. The average accuracy of mapping, i.e., the accuracy with which the ANN has
      mapped the normal and ischemic cuboids using the functional parameters, was 87.5%
      +/- 7.8 (s.d.). This accuracy was superior to the accuracy obtained by optimal
      thresholding of the same thickening (80.1%) and endocardial strain (76.9%) data.

PMID- 8987267
TI  - An automatic technique for finding and localizing externally attached markers in
      CT and MR volume images of the head.
AB  - An image processing technique is presented for finding and localizing the
      centroids of cylindrical markers externally attached to the human head in
      computed tomography (CT) and magnetic resonance (MR) image volumes. The centroids
      can be used as control points for image registration. The technique, which is
      fast, automatic, and knowledge-based, has two major steps. First, it searches the
      entire image volume to find one voxel inside each marker-like object. We call
      this voxel a "candidate" voxel, and we call the object a candidate marker.
      Second, it classifies the voxels in a region surrounding the candidate voxel as
      marker or nonmarker voxels using knowledge-based rules and calculates an
      intensity-weighted centroid for each true marker. We call this final centroid the
      "fiducial" point of the marker. The technique was developed on 42 scans of six
      patients-one CT and six MR scans per patient. There are four markers attached to
      each patient for a total of 168 marker images. For the CT images the false marker
      rate was zero. For MR the false marker rate was 1.4% (Two out of 144 markers). To
      evaluate the accuracy of the fiducial points, CT-MR registration was performed
      after correcting the MR images for geometrical distortion. The fiducial
      registration accuracy averaged 0.4 mm and was better than 0.6 mm for each of the
      eighteen image pairs.

PMID- 8987268
TI  - Accurate measurement of three-dimensional knee replacement kinematics using
      single-plane fluoroscopy.
AB  - A simple extension of a previously reported object recognition technique has been
      used to implement a six-degree-of-freedom position/orientation estimator for the
      measurement of knee replacement motion from two-dimensional (2-D) fluoroscopic
      images. Computer modeling studies and controlled mechanical tests were performed
      to assess the accuracy of the technique. The results indicate that knee rotations
      can be measured with an accuracy of approximately one degree and that sagittal
      plane translations can be measured with an accuracy of approximately 0.5 mm. The
      measurement technique is uniquely well suited for performing dynamic kinematic
      measurements on individuals with knee replacements, and for performing
      comparative studies among subjects with different designs of knee replacements.

PMID- 8987269
TI  - A modified boundary element method for the estimation of potential fields on the
      scalp.
AB  - A modified boundary element method (BEM) for the calculation of potential fields
      on the scalp is proposed and tested in a three-shell model. The method greatly
      reduces the computational burden with only a small cost in accuracy. The
      resistivity of the skull is taken as infinite and the potential field on the
      inner skull surface is calculated using the standard BEM method for a one-surface
      system. Then the potential at any single selected point on the scalp is
      calculated directly from Green's theorem. The method does not give an accurate
      estimate of the magnitude of the potential on the scalp, but it does preserve
      correct relative magnitudes over all source locations in the head.

PMID- 8987270
TI  - Examination of epimysial leads used to stimulate the latissimus dorsi muscle.
AB  - Cardiomyoplasty is a new surgical treatment for heart failure in which the
      patient's latissimus dorsi muscle (LDM) is isolated, wrapped around the heart,
      and electrically stimulated to provide cardiac assistance. At present, long term
      stimulation of the LDM is achieved with intramuscular electrodes, which produce
      minimal nerve damage. This study examined the use of epimysial electrodes by
      measuring the epimysial lead characteristics during a four-week LDM training.
      Lead resistance started at 463 +/- 41 omega after implantation, decreased during
      the following week (251 +/- 16 omega), and remained less than the initial value
      during the last three weeks (weeks two: 282 +/- 19 omega and week four: 341 +/-
      28 omega). The recruitment properties were similar to nervecuff electrodes: low
      threshold voltages (week one: 0.75 +/- 0.12, week two: 0.90 +/- 0.33, week four:
      0.52 +/- 0.10 V) and a very steep recruitment curve with low saturation voltages.
      Histological examination revealed normal muscle fibers with no inflammatory
      response. Epimysial leads may be more convenient for most surgeons because the
      design does not require any free-dissection of the nerve nor guiding a needle
      around the nerve with the risk of perforating vessels or nerve branches. These
      results indicate that epimysial leads are worthy of further investigation.

PMID- 8987271
TI  - The cap-choke catheter antenna for microwave ablation treatment.
AB  - A matched-dipole type catheter antenna is described for intracavitary and/or
      transluminal microwave treatment of diseases that may be responsive to thermal
      ablation therapy. This cap-choke antenna consists of an annular cap and coaxial
      choke design that can yield SAR distributions in and can produce heating of
      tissue surrounding the distal end of the catheter antenna. The cap-choke antenna
      is simple in construction, provides the desired specific absorption rate (SAR)
      distribution, and is efficient, i.e., the measured power reflection coefficient
      is 2% in tissue equivalent phantom modeling materials.

PMID- 8987272
TI  - Effects of low charge injection densities on corrosion responses of pulsed 316LVM
      stainless steel electrodes.
AB  - The safe charge injection density for pulsing of 316LVM electrodes has been
      reported to be 40 microC/cm2. However, only 20 microC/cm2 is available for
      nonfaradic charge transfer and double layer charge injection. Therefore, we
      evaluated long term pulsing at 20 microC/cm2 with capacitor coupling.

PMID- 8987273
TI  - Linear hydraulic pressure-pulse actuator (LHPA): a versatile instrument that
      produces a simulated blood pressure pulse wave for small sized vessels.
AB  - An instrument is presented which produces a simulated circulatory pulsatile
      pressure wave for small sized vessels. The linear hydraulic pressure-pulse
      actuator (LHPA) is designed to be extremely versatile, that is, a blood pressure
      wave source of any shape, amplitude, offset and frequency can be simulated. In
      addition, the LHPA can reproduce accurately a real pulse pressure wave by simply
      imputting an actual data record of a circulatory pressure pulse. The design is
      accomplished by incorporating the use of a linear force solenoid driven with a
      voltage-to-current source power amplifier. Testing of the device is presented
      here, as well as pressure pulse results from a recorded pulsatile pressure input
      to the LHPA. The device is simple to implement in that its response is linear,
      for volume changes upto +/- 5 mL, without the need for feedback compensation.

PMID- 8987274
TI  - Classifying nursing-sensitive patient outcomes.
AB  - This report describes research at the University of Iowa College of Nursing to
      develop a comprehensive classification of nursing-sensitive patient outcomes. The
      Nursing-Sensitive Outcomes Classification (NOC) completes the nursing process
      elements of the Nursing Minimum Data Set (NMDS). We describe resolution of
      conceptual and methodological problems that define the inductive approach taken
      to develop the NOC. Strategies used to develop NOC included review of the
      literature, clinical databases and instruments; concept analysis; and surveys of
      nurse experts. Examples of outcomes, definitions, and indicators are presented.
      The NOC provides standardized patient outcomes for determining the effectiveness
      of nursing interventions and enables inclusion of these data in data sets for
      healthcare effectiveness research.

PMID- 8987275
TI  - Nursing intervention classification systems.
AB  - PURPOSE: To analyze the features, development, and research of the Omaha System,
      the Iowa Nursing Intervention Classification, and the Home Health Care
      Classification and provide a critical review of the unique components of each.
      ORGANIZING FRAMEWORK: Five elements: achievement of original purpose, language
      used, ease of computerizing format, clinical utility, and linkage of the Nursing
      Minimum Data set (NMDS) nursing care elements. CONCLUSIONS: Further testing and
      development of nursing classification systems should be done to determine the
      general value of nursing classification, the extent to which the original goals
      and purposes of classification are met, and to identify the unique features and
      contributions of each system. Further testing is important to determine the
      strengths, weaknesses, and applicability of the various systems for capturing the
      elements of the NMDS for different care settings, care givers, and patient
      populations. IMPLICATIONS: Nursing classification may eventually lead to naming
      and describing the work of nurses. Research findings will continue to provide
      information leading to a unified nursing language system that describes the
      practice of nursing in local, regional, national, and international health-care
      data sets used for research, clinical, education, policy, and administrative
      purposes.

PMID- 8987276
TI  - Toward a model for nursing informatics.
AB  - PURPOSE: To propose a new model for the development of nursing informatics based
      on historical precedent. SIGNIFICANCE: Nursing informatics is expanding rapidly.
      The proposed model aids in understanding the areas of research, relating them to
      each other, and it shows areas where work is missing or should be extended.
      ORGANIZING FRAMEWORK: Nursing informatics as the interaction of cognitive
      science, computer science, and information science resting on a base of nursing
      science. IMPLICATIONS: As this model is tested, it can act as an organizing
      framework to understand and relate studies of nursing informatics and give
      organization for future research, education, and development.

PMID- 8987277
TI  - Life-span perspective of personality in dementia.
AB  - PURPOSE: To propose an alternative view of personality change in dementia by
      presenting existing evidence for the continuity of personality. SIGNIFICANCE: As
      the population continues to age, dementing illnesses will account for a greater
      proportion of morbidity and mortality; the care of these people will have a
      significant effect on the health care system. ORGANIZING FRAMEWORK: Life-span
      perspective of personality continuity. SCOPE METHOD: Review of current literature
      on personality in dementia using Medline, 1980-1994; CINAHL, 1990-1994; and Psych
      Lit., 1980-1994. FINDINGS: Although there are systematic shifts in personality
      with dementia, individuals tend to maintain their unique pattern of premorbid
      personality traits. CONCLUSIONS: The personalities of dementia patients seem to
      reflect adaptive patterns that served them in the past. IMPLICATIONS: Use of a
      life-span perspective can enhance individualized care for demented patients and
      advance theory development.

PMID- 8987278
TI  - HIV/AIDS related knowledge, attitudes, and preventive behavior of pregnant Korean
      women.
AB  - OBJECTIVE: To assess HIV-AIDS-related knowledge, attitudes, and preventive
      behavior of pregnant Korean women before designing patient and public education
      programs. DESIGN: Pre-experimental cross-sectional survey. POPULATION, SAMPLE,
      SETTING, YEARS: Convenience sample of 409 women at six prenatal clinics in Seoul,
      Korea, in 1993. OUTCOME MEASURES: HIV-AIDS-related knowledge, attitudes, and
      preventive behavior. METHODS: Self-administered questionnaires. FINDINGS: The
      women described high levels of knowledge about HIV and AIDS risk factors but less
      knowledge about transmission of the virus, as well as attitudes of rejection
      toward unrelated people with HIV/AIDS; 16% provided condoms for their husband's
      use in extramarital sex, the primary risk behavior. CONCLUSIONS: Korean women are
      at risk for heterosexual transmission of HIV despite knowledge of risk factors.
      CLINICAL IMPLICATIONS: Korean education programs for women should focus on modes
      of heterosexual transmission, care of individuals with HIV or AIDS, self
      assessment of HIV-AIDS risk, and self protection.

PMID- 8987279
TI  - Healing of adult male survivors of childhood sexual abuse.
AB  - OBJECTIVE: To generate a framework of healing by male survivors of childhood
      sexual abuse. DESIGN: Qualitative using grounded theory methodology. POPULATION,
      SAMPLE, SETTING, YEARS: Population was American men living in the community who
      have experienced some healing from childhood sexual abuse. Sample was 19 men who
      were recommended by area therapists or who had publicly identified themselves as
      survivors. Participants were interviewed in 1993 and 1994. METHOD: Formal,
      unstructured interviews using open-ended questions. FINDINGS: The core variable
      that emerged was "Escaping the dungeon: The journey to freedom." The metaphor of
      "dungeon" reflects the men's experiences of powerlessness, isolation, silence and
      darkness, shame, and pain from their abuse. Healing was described as breaking
      free, living free, and freeing those left behind. CONCLUSIONS: Healing involves a
      struggle against an internal force, emotional pain, and against an external
      force, the sociocultural prescription that men should not be victims. CLINICAL
      IMPLICATIONS: Clinicians working with adult male survivors should consider the
      pervasive effects of some childhood sexual abuse experiences. Therapists can
      address the intrapsychic wounds of male survivors while acknowledging the context
      of their healing, a society where the victimization of men is often invalidated.

PMID- 8987280
TI  - Advancing nursing practice with a unit-based clinical expert.
AB  - OBJECTIVE: To explore patterns in the practice of nursing and patient outcomes.
      DESIGN: Qualitative field research. POPULATION, SAMPLE, SETTING: Populations were
      critical care nurses and critically ill adult patients in the 10-bed medical
      critical care unit of a 900-bed teaching hospital. A convenience-purposive sample
      of 27 nurses and 31 patients was studied in 1985. METHODS: Six months of
      participant observation, unstructured interviews, and the constant comparison
      method of grounded theory. FINDINGS: Markedly different patterns were found in
      expert and nonexpert practice. The substantive theory of conversion helped
      explain how the majority of nonexpert nurses advanced their practice. The
      metaphor of catalyzed conversion captures how a unit-based expert nurse serves as
      a catalyst to advance the practice of nonexperts. Presence, defined as the way of
      being within a given clinical context, differentiated nurses. CONCLUSIONS: (a)
      Expert and nonexpert practices are substantively different. (b) Expert and
      nonexpert practice results in different patient outcomes. (c) Conversion helps
      explain changes in nonexpert practice. CLINICAL IMPLICATIONS: A unit-based expert
      nurse can increase patient-focused care.

PMID- 8987281
TI  - Interviews with seven holders of endowed chairs in nursing.
AB  - OBJECTIVE: To describe the activities of selected nurses holding endowed-chair
      positions and the development and funding of endowed chairs. DESIGN:
      Longitudinal, exploratory/descriptive. SAMPLE, SETTING, YEARS: Data were
      collected 1992-1995 from seven university nurses in five states. METHODS:
      Questionnaire and interviews. FINDINGS: Nurses holding endowed-chairs are highly
      committed to advancing nursing. There is an extremely high level of job
      satisfaction and also mobility into upper administrative positions. Activities
      commonly extend beyond the faculty role and involve working with local and
      national groups. CONCLUSIONS: The numbers and funding of endowed chairs in
      nursing are increasing. Holders are contributing significantly to the
      profession's advancement and to human welfare. IMPLICATIONS: Clinical practice
      and nursing's image are enhanced by the research and other scholarly activities
      of nurses holding endowed positions.

PMID- 8987282
TI  - Shared experiences and meanings of military nurse veterans.
AB  - OBJECTIVE: To determine the shared perceptions, feelings, and experiences of U.S.
      military nurse veterans. DESIGN: Phenomenological based on Heideggerian
      philosophy. POPULATION, SAMPLE, SETTING: The population was of military nurse
      veterans in the U.S.A. from World War II, Korea, Vietnam, and Operation Desert
      Storm. The convenience sample was 22 nurses recruited from local and national
      veterans' groups who volunteered to be interviewed. METHODS: Transcribed
      interviews with team members producing written interpretations; the team produced
      consensus about themes. Each interview was summarized and validation from the
      research team and respondents was sought. CONCLUSIONS: Five common themes or
      shared meanings emerged: reacting personally to the war experience, living in the
      military, the meaning of nursing in the military, the social context of war, and
      images and sensations of war. CLINICAL IMPLICATIONS: A coherent review of wartime
      nursing.

PMID- 8987283
TI  - Caring and comfort metaphors used by patients in critical care.
AB  - OBJECTIVE: To examine the meaning of metaphors used by critical care patients
      about their ventilator weaning experience. DESIGN: Grounded theory. POPULATION,
      SAMPLE, SETTING: In 1992-1993, from a population of mechanically ventilated
      patients, a convenience sample of 20 adult patients was recruited from one 14-bed
      multispecialty ICU in a 740-bed teaching hospital in eastern Canada. METHODS:
      Transcripts of interviews were reviewed from the 20 original study transcripts,
      of which 18 included one or more metaphors for a total of 70. All were coded and
      classified with sub-themes analyzed for implicit meanings. FINDINGS: Four
      categories of metaphors were Physical Discomfort, Nurse Caring, Altered Self, and
      Patient Work. Data provide the elements for a mid-range theory of caring.
      CONCLUSIONS: Metaphors provide vivid images of significant patient concerns and
      are a way for people to express meaning and feeling. CLINICAL IMPLICATIONS:
      People communicate about their inner world through language. Examining patients'
      metaphors is a valuable approach to understanding the experiential world of
      patients in critical care so that nursing actions can be directed toward personal
      needs which may not be expressed openly. Providing interventions aimed at these
      personal needs will help patients find suitable levels of physical and emotional
      comfort.

PMID- 8987284
TI  - Emerging model of quality.
AB  - A theoretical model of quality, based on an organismic worldview, provides a
      framework for understanding health care quality. This retroductively developed
      model incorporates ethical and economic concepts: value, beneficence, prudence,
      and justice. The model supports viewing patients and families as equal partners
      with providers in defining, evaluating, and achieving health care quality.
      Further model development can generate mid-range theories useful for improving
      quality in an ethical and economic manner.

PMID- 8987285
TI  - Serenity as a goal for nursing practice.
AB  - PURPOSE: To extend a conceptual analysis of serenity by explaining how serenity
      develops and to present an analysis of serenity interventions. SIGNIFICANCE:
      Serenity is highly desired by many. There is evidence that the experience of
      serenity improves health. The information presented proposes how nurses can use
      knowledge about serenity in practice. ORGANIZING FRAMEWORK: Serenity is viewed as
      a learned, positive emotion of inner peace that can be sustained. It is a
      spiritual concept that decreases perceived stress and improves physical and
      emotional health. SOURCES AND APPROACH: Results of a conceptual analysis of
      serenity, research findings related to development of a Serenity Scale, practice
      experience, and the literature provided a foundation for the analysis. Inductive
      reasoning and substruction were the primary methods of constructing the proposed
      relationships. A nursing practice example is included. CONCLUSIONS: The
      experience of serenity is related to development of the higher self. Four levels
      of serenity are a safe, wise, beneficent, and universal self. Knowledge about
      serenity can help nurses to select interventions that promote clients' health.

PMID- 8987286
TI  - Collaborative research by graduate students.
AB  - PURPOSE: Educators are challenged to prepare graduate students for future
      cooperative efforts by fostering collaboration. ORGANIZING FRAMEWORK: Assumptions
      and beliefs about collaborative research are examined and a definition and
      ethical considerations are suggested. A sample letter of agreement is also
      provided. CONCLUSIONS: Effective collaborative research is accomplished through
      planning and organization, and cannot be left to chance.

PMID- 8987287
TI  - Autonomic nervous system and asthma.

PMID- 8987288
TI  - A study of autonomic status and its effect on ventilatory functions in bronchial
      asthma.
AB  - The present study was undertaken to evaluate the autonomic nervous function in
      patients with bronchial asthma after indirect autonomic stimulation by seven
      different manoeuvres. A total of 30 cases of bronchial asthma and 20 healthy
      matched controls were studied after excluding all other diseases and drugs which
      could have a modulating effect on autonomic function. The tests used were: heart
      rate responses to the Valsalva manoeuvre, deep breathing, intravenous atropine,
      carotid sinus massage and standing from the supine position, and, the blood
      pressure responses to sustained handgrip and to standing from the supine
      position, the former five being tests of parasympathetic function and the latter
      two of sympathetic function. A significant difference in responses was observed
      in asthmatics who showed heightened cardiovascular responses to tests of
      parasympathetic function as compared to controls. Ventilatory function parameters
      (FVC and PEFR) also showed a parallel enhanced response (marked decrease) to
      parasympathetic stimulation by Valsalva manoeuvre, deep breathing and carotid
      sinus massage in asthmatics compared to controls. This aspect of differences in
      ventilatory response has not been previously reported in literature. No
      significant differences were found in the blood pressure responses to sustained
      handgrip and to standing from the supine position. Correlations between the
      autonomic status of the asthmatics with the clinical characteristics of the
      patients were analysed.

PMID- 8987289
TI  - Acute respiratory distress syndrome (ARDS) in miliary tuberculosis: a twelve year
      experience.
AB  - Miliary tuberculosis [MTB] is an uncommon but important treatable cause of acute
      respiratory distress syndrome [ARDS]. In this communication, six patients with
      MTB who developed ARDS in the course of their illness are described. The
      difficulties encountered in diagnosing MTB as a primary cause of ARDS are
      highlighted. The pathogenetic mechanisms of ARDS in MTB are briefly reviewed.

PMID- 8987290
TI  - Fluoroscopic transbronchial fine needle aspiration for diagnosis of peripheral
      pulmonary nodules.
AB  - Transbronchial fine needle aspiration (TBNA) was performed under fluoroscopic
      guidance in 21 patients with either solitary (15 patients) or multiple (6
      patients) peripherally located nodules. Good aspirate could be obtained in 16
      patients (76.1%). Ten were confirmed to be malignant and 2 turned out to be
      tubercular. Nonspecific benign inflammatory aspirate was obtained in the other
      four. There were no significant complications. TBNA is thus an effective, safe
      and quick method for diagnosis of solitary/multiple pulmonary nodules.

PMID- 8987291
TI  - Tropical pulmonary eosinophilia.

PMID- 8987292
TI  - The CV Raman Medal (1995) Award Lecture. New knowledge about exertional
      breathlessness: use and misuse.

PMID- 8987293
TI  - Superior mediastinal mass in a 14-year-old male child.

PMID- 8987294
TI  - Pulmonary nocardiosis.
AB  - A case of pulmonary nocardiosis is described in a patient who had alcoholic
      cirrhosis of liver and portal hypertension. The patient also had diffuse
      proliferative glomerulonephritis and was on prednisolone treatment.

PMID- 8987295
TI  - Syndrome of primary ciliary dyskinesia: Kartagener's syndrome with empyema
      thoracis and azoospermia.
AB  - Primary ciliary dyskinesia is a genetically determined disorder with several
      pulmonary complications. A case of an 18-year-old male suffering from this entity
      and having empyema thoracis and azoospermia is presented here.

PMID- 8987296
TI  - Unilateral pulmonary hypoplasia with bifid ureter and pelvis.

PMID- 8987297
TI  - Pneumomediastinum, pneumothorax and subcutaneous emphysema with kerosene oil.

PMID- 8987298
TI  - Plain word.

PMID- 8987299
TI  - What is the INR?

PMID- 8987300
TI  - Patient and dentist: a unique dental care partnership.

PMID- 8987301
TI  - It's about risk.

PMID- 8987302
TI  - Advanced instant photography.
AB  - With the popularization of cosmetic and esthetic dental procedures, the
      importance of various photographic techniques has increased. The dentist's choice
      of a particular system depends on whether the intended use of the dental image is
      to assist in treatment acceptance, or to use the patient's "initial phase of
      excitement" to contribute to photomarketing. This paper uses before-and-after
      photos to demonstrate a dramatic alteration of the patient's smile.
      Photomarketing may be enhanced through the introduction of instant cameras,
      including the Polaroid Macro 5 SLR.

PMID- 8987303
TI  - Posterior acid-etch bridge--a modified retentive design.
AB  - This article reviews the recent literature on clinical trial studies of acid-etch
      bridges. Due to long-term retention problems, acid-etch bridges are not as yet
      considered among the permanent types of bridge prosthesis. When failure of acid
      etch bridges occurs, the weak link seems to be the enamel-resin junction rather
      than the metal-resin junction. A modified posterior acid-etch bridge design is
      described in detail. This design, which incorporates a major retention-promoting
      component, is meant to improve long-term retention of posterior acid-etch
      bridges. Cast projections are added to the bridge design. These fit loosely into
      slot cavities made in the abutment teeth. Following bridge cementation, the slot
      cavities are restored with posterior composite. As a result, the cast metal
      projections are locked into the abutment teeth. This added retention device will
      maximize the long-term retention of posterior acid-etch bridges.

PMID- 8987304
TI  - Progress in HIV and AIDS care.
AB  - These recent meetings emphasized the considerable progress that has been made in
      HIV/AIDS. The prospect for non-progression of the disease, improved management of
      complications arising from the condition, and the potential for additional
      progress were the hallmarks of these meetings. The considerable developments that
      have occurred make it necessary for the dental profession to continue to play a
      role in the recognition, diagnosis, and management of oral conditions, and to
      keep abreast of the considerable developments in this field-and the implications
      that these developments have for patients presenting with complications related
      to other conditions, which may include bacterial, fungal or viral infections and
      malignant disease.

PMID- 8987305
TI  - Repair of washout defects.
AB  - Endodontic therapy may be needed after extensive fixed partial denture treatment.
      When endodontic access preparation is performed through a cast restoration,
      retention of the restoration is reduced and the underlying abutment structure may
      be weakened. Eventually, it may give way to cement breakdown and caries,
      resulting in a washout defect, which can jeopardize the restoration's longevity.
      This paper describes the clinical management of such a situation using stainless
      steel prefabricated posts and a bonding cement.

PMID- 8987306
TI  - A clean break: exiting dental partnerships.

PMID- 8987308
TI  - Performance improvement just got easier.

PMID- 8987307
TI  - The building blocks for quality care.

PMID- 8987309
TI  - Responsibility matrix for clinical pathways.

PMID- 8987310
TI  - Preventing worker injuries.

PMID- 8987311
TI  - Quality evaluations made easy and meaningful.

PMID- 8987312
TI  - Six steps to maximizing HEDIS results.

PMID- 8987313
TI  - Spanning organizational boundaries to improve care and service: inpatient and
      outpatient chronic peritoneal dialysis.
AB  - The University of Michigan Health Systems (UMHS), an academic, tertiary care
      health system, provides chronic peritoneal dialysis (PD) along an inpatient
      outpatient continuum that gives patients access to an integrated system of
      settings, services, and care levels. An evaluation of key indicators was
      conducted to determine the quality of PD services as chronic dialysis clients
      were admitted to one UMHS inpatient unit. The challenge of matching the chronic
      PD patient's needs with the appropriate level of care along the health care
      continuum was addressed. This information presents an effective way to use
      quality data to improve PD care practices and patient outcomes.

PMID- 8987315
TI  - Redesign for patient satisfaction.
AB  - In this era of changing health care systems, the word redesign is often linked
      with mergers, layoffs, or an economic move to balance the bottom line. Redesign
      is often perceived as a way to reduce the need for professional nurses by
      eliminating job functions. In this cost-cutting milieu, however, the most
      important factor--the patient--has been put aside. The article explores what
      factors contribute to patient satisfaction and describes the redesign process
      that was implemented at one institution to increase patients' satisfaction during
      hospitalization.

PMID- 8987314
TI  - Model for a nursing center: spanning boundaries.
AB  - The article provides an example of spanning organizational and professional
      boundaries to improve care in a medically underserved community through the
      development of a nursing center. Descriptions of the practice and organizational
      models demonstrate how each was tailored to the specific community. Using
      Andersen's behavioral model of families' use of health services and objectives
      for the year 2000, the impact on access to care and population outcomes are
      evaluated.

PMID- 8987316
TI  - Determining the effectiveness of critical pathways for coronary artery bypass
      graft patients: retrospective comparison of readmission rates.
AB  - The article describes a study performed to determine whether the use of the
      critical path tool made a difference in the readmission rates of patients after
      coronary artery bypass graft (CABG) surgery compared with CABG patients cared for
      without the critical path tool. The sample for this retrospective study consisted
      of 780 specific patient medical records from the medical record department.
      Examination of the data revealed no statistically significant difference in
      readmission for CABG patients cared for with critical paths and those cared for
      without critical paths. A comparison of hospital length of stay and surgical
      length of stay between the two groups however, revealed statistically significant
      differences between the two groups. The critical path group had a significant
      decrease in hospital and surgical length of stay.

PMID- 8987317
TI  - A patient-focused pathway for ambulatory anticoagulation care.
AB  - Careful monitoring of ambulatory patients on anticoagulation medication is
      essential to prevent serious complications such as hemorrhages or blood clots.
      Nurse-run clinics developed in the 1980s provided some of the assistance
      necessary for chronic maintenance. These clinics had systems problems, however,
      that were frustrating for both the nurse and the patient. The article describes
      how multidisciplinary involvement at one medical center helped develop an
      anticoagulation pathway that improved service to patients and clarified and
      strengthened the nurse's role in the pathway.

PMID- 8987318
TI  - Clinical pathway implementation in the acute care hospital setting.
AB  - A study was conducted to assess the current status of clinical path
      implementation for acute care cases and to explore implementation issues related
      to defining discharge outcomes and measuring variances in clinical paths. Results
      indicated that documentation, identification of critical indicators and discharge
      outcomes, and variance detection and correction are three core issues that must
      be addressed by institutions that implement clinical paths. A discussion of each
      of these areas is provided.

PMID- 8987319
TI  - Altered skin integrity in children admitted to a pediatric intensive care unit.
AB  - As part of a quality improvement study, the incidence and severity of altered
      skin integrity in a tertiary pediatric intensive care unit (PICU) were
      investigated in an attempt to identify contributing risk factors. Demographic,
      severity of illness, and practice variables were collected on 271 of 357
      admissions during an 18-week period. Data were analyzed from the date of PICU
      admission until a change in skin integrity occurred or until PICU discharge.
      Altered skin integrity occurred in 26 percent of admissions; 7 percent of the
      cases had skin breakdown. By multivariate analysis, only the Pediatric Risk of
      Mortality Score and white race were associated with altered skin integrity.

PMID- 8987320
TI  - The clinical efficacy of gamete intrafallopian transfer by minilaparotomy versus
      in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: To evaluate the clinical performance of gamete intrafallopian transfer
      (GIFT) and in vitro fertilization and embryo transfer (IVF-ET). METHODS:
      Infertile women were divided into 2 groups: for GIFT, 239 patients (326 cycles)
      with at least 1 patent tube; and, for IVF-ET, 125 patients (210 cycles) with
      bilateral tubal occlusion. A specially designed retractor was developed to
      replace the gametes into an appropriate section of the Fallopian tube accurately
      and safely. Several parameters, including the pregnancy and delivery rates of
      each group, were compared. RESULTS: The success rate per trial in the GIFT group
      was approximately 1.5 times higher than that in the IVF group (pregnancy rate:
      44.2% vs. 31.0%, p < 0.01; delivery rate: 33.4% vs. 22.9%, p < 0.01). The
      pregnancy and delivery rates of GIFT decreased steadily with the number of
      trials. These apparent decreases were not observed up to the 3rd trial in IVF-ET
      cases. CONCLUSIONS: GIFT with a minilaparotomy procedure yielded significantly
      higher success rates than IVF-ET. Accordingly, GIFT is considered to be the first
      treatment choice in infertility cases with at least 1 patent Fallopian tube.

PMID- 8987321
TI  - The prevalence of hemoglobin S and glucose-6-phosphate dehydrogenase deficiency
      in Jordanian newborn.
AB  - OBJECTIVE: The aim of this study was to determine the incidence of HbS and
      glucose-6-phosphate dehydrogenase (G6PD) deficiency in Jordanian newborn. STUDY
      DESIGN: A total of 181 male and female babies born at Princess Basma Teaching
      Hospital, randomly selected, and cord blood samples were collected, and the
      erythrocyte G6PD activity was measured, and the hemoglobin electrophoresis for
      blood lysate was conducted and scanned for HbS scanning. RESULTS: The frequencies
      of two major red cell genetic defects, sickle hemoglobin (HbS) and deficiency
      G6PD was determined, of the studied subjects 10 (11%) females and 11 (12%) males
      were found to be deficient in the G6PD gene. The frequency of HbS carriers among
      the females was 4% while it was 6% among males. The coincidence of both G6PD
      deficiency and sickle cell hemoglobin in the samples was 1%. No coincidence was
      found between G6PD deficiency and hyperbilirubinemia. CONCLUSION: A better
      understanding of the distributions of these genetic disorders has the potential
      to aid in the more efficient utilization of health care resources and improved
      planning.

PMID- 8987322
TI  - Pulmonary embolism associated with Sjogren's syndrome in pregnancy.
AB  - The occurrence of pulmonary embolisms in patients having circulating lupus
      anticoagulant has been reported. Lupus anticoagulant has been noticed in
      association with autoimmune diseases and early-onset severe preeclampsia. We
      report a case of Sjogren's syndrome with circulating lupus anticoagulant in a
      patient who developed a pulmonary embolism and severe preeclampsia at 29 weeks of
      gestation.

PMID- 8987323
TI  - Calcium supplementation and prevention of pregnancy induced hypertension.
AB  - In a randomized controlled trial 201 healthy nulliparous women were randomly
      allocated by means of a computer generated randomization list. From 20 weeks of
      gestation until delivery they received either 2 g of oral elemental calcium (n =
      103) per day or an identical placebo (n = 98). Eleven women (5.47%) were lost to
      follow-up after randomization. The study groups were very similar at the time of
      randomization; with respect to several clinical and demographic variables.
      Treatment compliance was very similar in both groups as was determined by pill
      count. The rate of pregnancy induced hypertension was lower in the calcium group
      than in the placebo group 8.24%; vs 29.03%; (RR = 0.28; 95% CI 0.14-0.59). The
      incidence of gestational hypertension was 6.18% in the calcium group and 17.20%
      in the placebo group (RR = 0.28; 95% CI 0.08-0.80), and the incidence of
      preeclampsia was 2.06% in the calcium group and 11.82% in the placebo group (RR =
      0.13; 95% CI 0.01-0.64). In conclusion calcium supplementation given in pregnancy
      to nulliparous women reduces the incidence of pregnancy induced hypertension.

PMID- 8987324
TI  - Outcome of unplanned vaginal deliveries after two previous caesarean sections.
AB  - Once a caesarean section always a caesarean section may not stand true any more
      but twice a caesarean section always a caesarean section still stays put because
      of its high maternal and foetal complications. Jinnah Postgraduate Medical Centre
      is large tertiary care hospital and has a caesarean section rate of over 18%, 10
      patients (3.9%) were picked up in a retrospective study who had vaginal delivery
      after 2 previous caesarean sections in 2 years. They were admitted late in
      labour. Only one patient had dehiscence of scar. The aim of the study was to
      evaluate the outcome and safety of vaginal deliveries after 2 previous caesarean
      sections even when the trial was not conducted at the hospital.

PMID- 8987325
TI  - Uterine cervical clear-cell adenocarcinoma with a choriocarcinomatous component:
      a case report.
AB  - A 55-year-old woman presented with vaginal bleeding. A tumor was found in the
      cervix; it was composed of 2 distinctive elements: a clear-cell adenocarcinoma
      and a choriocarcinoma. Histologic findings suggested that the choriocarcinomatous
      element was derived from a preexisting clear-cell adenocarcinoma through a
      metaplastic process.

PMID- 8987327
TI  - Absence of vagina and hypoplasia of the urethra and ectopia of the ureter.
AB  - A 16-year-old Japanese girl was admitted for evaluation of complaints of primary
      amenorrhea, cyclic lower abdominal pain, and urinary incontinence. Her vaginal
      introitus appeared rudimentary with a depth of 0.5 cm and hypoplasia of the
      hymenal ring. A hypoplastic urethra (diameter: 1 cm; length: 0.5 cm) and 1 of 2
      right ectopic ureters opened into the introitus. Transabdominal ultrasonography
      demonstrated fluid distending the uterus, the proximal 1/3 of the vagina, and the
      pouch of Douglas. Computed tomography (CT) and magnetic resonance imaging (MRI)
      confirmed the presence of hematometrocolpos and fluid collection in the pouch of
      Douglas. These associated anomalies can be due to faulty growth of the urogenital
      sinus. In addition to the transabdominal ultrasonography and CT, MRI was useful
      in the diagnosis and evaluation of vaginal agenesis.

PMID- 8987326
TI  - The value of human growth hormone as an adjuvant for ovarian stimulation in a
      human in vitro fertilization program.
AB  - The purpose of this study was to evaluate whether the combined treatment of
      growth hormone (GH) and gonadotropins can improve ovulation stimulation in
      previously poor responders. Twelve patients who, had suboptimal responses in
      previous in vitro fertilization cycle were enrolled. They underwent 1 cycle with
      gonadotropin-releasing hormone analogue (GnRH-a) and gonadotropins and another
      cycle with GnRH-a, gonadotropins, and GH. Serum gonadotropins, insulin-like
      growth factor-1 (IGF-1), and sex steroids, including estradiol (E2), progesterone
      (P4), testosterone, and androstenedione were measured on Day 2 and during
      ovulation induction. The serum IGF-1 level was higher in the GH cycle. There were
      no significant differences in the levels of the serum luteinizing hormone, E2,
      P4, testosterone, and androstenedione between the 2 cycles, so was IGF-1, E2 and
      P4 in follicular fluid. Co-treatment with GH did not improve the ovarian
      response. However, the GH cycles had better performance in terms of the number of
      oocytes fertilized and the pregnancy rate.

PMID- 8987328
TI  - The role of transvaginal ultrasonography and colour Doppler imaging in the
      detection of ectopic pregnancy.
AB  - OBJECTIVE: To assess the use of transvaginal ultrasound and colour Doppler
      imaging in the detection of ectopic pregnancy. MATERIALS AND METHODS: Seventy-one
      patients with suspected ectopic pregnancies had transvaginal sonography and
      colour Doppler imaging performed and 61 ectopic pregnancies were confirmed at
      surgery. Various ultrasound features on transvaginal B mode scanning were noted
      and the resistance index of peritrophoblastic flow in the adnexal masses
      computed. RESULTS: The use of transvaginal B mode imaging alone in the diagnosis
      of ectopic pregnancy achieved a sensitivity of 98% and a positive predictive
      value of 86%. The mean gestational age at time of diagnosis was 6 weeks 5 days
      (range 4 weeks to 13 weeks 2 days). The use of transvaginal colour flow imaging
      did not increase detection rates of ectopic pregnancy. The mean RI values for
      patients with or without ectopic pregnancy were almost identical. CONCLUSION:
      Colour Doppler imaging failed to improve on the results of transvaginal B mode
      sonography in the detection of ectopic pregnancy.

PMID- 8987329
TI  - Mucinous cystadenocarcinoma with sarcoma-like mural nodules arising in a mature
      cystic teratoma of the ovary: a case report.
AB  - Almost all cases with malignant transformation of a mature cystic teratoma of the
      ovary have been reported to be associated with squamous cell carcinoma. We
      describe a very rare case of mucinous cystadenocarcinoma with sarcoma-like mural
      nodules arising in an ovarian teratoma.

PMID- 8987330
TI  - Genital Chlamydia trachomatis infection in Egyptian women: incidence among
      different clinical risk groups.
AB  - OBJECTIVE: To investigate genital Chlamydial infection incidence among high risk
      clinical conditions in Egyptian women. METHODS: A case control study in Ain Shams
      University Hospital involving 501 patients with cervicitis (n = 58), abnormal
      cervical smear (n = 256), tubal infertility (n = 85), ectopic pregnancy (n = 22),
      preterm labour (n = 80) and 192 controls. Active cervical Chlamydial infection
      was diagnosed using direct immunofluorescent technique. Data were analyzed by Chi
      square (chi 2) and Z tests. RESULTS: Significant increase of Chlamydial infection
      among different clinical conditions compared to controls. The percentage of
      positive chlamydial infection was 79.3% among cervicitis group, 33.3% among
      subjects with inflammatory smear, 75.2% among those with cervical condyloma,
      82.6% among those with cervical intraepithelial neoplasia, 51.8% among tubal
      infertility subjects, 77.2% among ectopic patients and 56.3% among subjects with
      preterm labour. CONCLUSION: The incidence of Chlamydial infection in these high
      risk Egyptian patients is relatively high. Emperical treatment is recommended as
      the diagnosis is costly and usually not available.

PMID- 8987331
TI  - Assessment of tubal patency by transvaginal sonographic hydrotubation with color
      Doppler flow.
AB  - OBJECTIVE: To assess the value of transvaginal sonographic hydrotubation with
      color Doppler flow (TSH) as a test of tubal patency. METHODS: Thirty-nine women
      undergoing infertility investigation at Chulalongkorn Hospital participated in
      this prospective, blind comparative study. Before diagnostic laparoscopy (DL)
      with chromopertubation, TSH was performed using the SSD 680, 5 MHz vaginal
      ultrasound probe and 20-50 ml of saline was injected into the uterine cavity.
      RESULTS: Nine cases could not be evaluated properly. Of the 30 cases, there were
      complete agreements between TSH and DL in 24 (80%), partial agreement in 5
      (16.67%) and non-agreement in 1 (3.33%). TSH had sensitivity 100%; specificity
      84.62%, positive predictive value 50%, negative predictive value 100%, false
      positive rate 15.38%, but no false negative rate. CONCLUSION: TSH is a simple
      diagnostic procedure for screening of tubal patency. However, other confirmatory
      test is needed if tubal occlusion is suspected.

PMID- 8987332
TI  - A method of measuring dipalmitoylphosphatidylcholine (DPPC) by high-performance
      liquid chromatography (HPLC): effect of dexamethasone on DPPC secretion in fetal
      rat alveolar type II cell culture.
AB  - OBJECTIVE: To establish a method by which to measure
      dipalmitoylphosphatidylcholine (DPPC), which is the most prevalent phospholipid
      in lung surfactant, by high-performance liquid chromatography (HPLC), and to
      measure DPPC secretion in type-II alveolar cell culture to determine whether
      glucocorticoid has a direct accerelating effect. METHOD: Type-II alveolar cell
      suspensions were made with fetal rat lungs and then cultured. Dexamethasone, (10(
      9), 10(-8) M) was added to some of the culture dishes. DPPC was extracted from
      the culture medium, purified, and measured by high-performance liquid
      chromatography (HPLC). RESULTS: In the measurements of DPPC, the specificity of
      isolation and measurement parity were excellent [coefficient of variation:
      intraassay; 5.66% (0.005 mg/ml), 25.37% (0.05 mg/ml): interassay; 8.35% (0.005
      mg/ml), 0.08% (0.05 mg/ml)]. The DPPC concentration in the culture dishes of the
      dexamethasone was not significantly different than that of the control dishes
      (Student's t-test). CONCLUSION: The above results prove that dexamethasone does
      not directly stimulate lung alveolar type-II cells.

PMID- 8987333
TI  - Doppler-velocity waveforms in ductus venosus in normal and small-for-gestational
      age fetuses.
AB  - OBJECTIVE: To investigate blood-flow patterns in ductus venosus in growth
      retarded fetuses. METHODS: Reference ranges of ductus venosus flow velocities
      were constructed from a cross-sectional study of 179 normal fetuses between 16 to
      38 weeks' gestation. and the ductus venosus flow-velocity waveforms in 11 small
      for-gestational-age (SGA) fetuses were compared with normal patterns. RESULTS: Of
      179 pregnant women who were possible subjects, 175 were employed for the
      analysis, and ductus venosus flow-velocity waveforms were obtained in 197 out of
      211 examinations (success rate = 93.4%). The peak forward velocities during (a)
      ventricular systoles, (b) the lowest forward velocities during atrial
      contractions, and (c) the time-averaged velocities all linearly increased as
      gestational ages increased [respectively: (a) slope, 1.135; constant, 31.720; (b)
      slope, 1.154; constant, 1.557; (c) slope, 1.240; constant, 19.386]. Peak forward
      velocities during ventricular systoles and time-averaged velocities in the SGA
      group did not differ from those of the normal group. Three SGA fetuses with
      abnormal flow in the umbilical artery showed a marked reduction of the lowest
      velocities during atrial contractions in the ductus venosus, and two of them
      showed no forward velocity at all. CONCLUSION: The Doppler-velocity waveforms of
      ductus venosus showed a marked reduction of the end diastolic flow, especially in
      SGA fetuses with abnormal umbilical artery flows.

PMID- 8987334
TI  - Correlation between the stimulatory effect of oxytocin on the formation of
      inositol phosphates and the oxytocin receptor level in the pregnant rabbit
      myometrium.
AB  - OBJECTIVE: In order to elucidate the roles of inositol trisphosphate (IP3) and
      oxytocin (OT) receptors in rabbit parturition, the concentration of IP3 induced
      by OT and the OT receptor levels were determined in rabbit myometria before and
      after parturition. METHODS: The effects of OT on IP3 formation and OT receptor
      levels were determined in the myometria of non-pregnant rabbits, Days 26, 28 and
      30 of pregnancy rabbits, postpartum rabbits within 12 hours and steroid-treated
      ovariectomized rabbits. Prostaglandins (PGs) levels were also measured in the
      myometrial and decidual tissues. RESULTS: OT receptors were not detectable in the
      myometria of non-pregnant rabbits, and OT had no effect on the formation of
      inositol phosphates (IPs). On Day 28 of pregnancy, OT receptors became
      detectable, and then OT could induce the formation of IPs. Thereafter, the
      stimulatory effects of OT on IPs formation and the OT receptor levels
      dramatically increased toward the end of pregnancy and reduced rapidly after
      parturition. When the ovariectomized pregnant rabbits were treated with estrogen,
      OT receptors in the myometrium were induced, and OT acquired the ability to
      stimulate IP3 formation. However, OT had no effect on the production of cAMP,
      cGMP, prostaglandin (PG) E2 and F2 alpha in the myometria, even if receptors
      existed, although PGE2 production in the decidual tissues was markedly
      stimulated. In addition, an OT receptor antagonist inhibited the stimulatory
      effects of OT on IP3 formation. CONCLUSIONS: These results suggest that the
      formation of IPs by OT, the OT receptor levels in the myometrium, and the
      production of PGF2 in the decidua might play crucial roles in parturition.

PMID- 8987335
TI  - Regulation of neutrophil superoxide generation by alpha-tocopherol in human
      peripheral and umbilical-cord blood.
AB  - OBJECTIVES: Alfa-tocopherol (VE) inhibits protein phosphorylation and affects
      protein kinase C (PKC)-dependent superoxide (O2) generation of phagocytic cells.
      Because umbilical-cord blood contains low concentrations of VE, we studied the
      effects of VE on stimulation-dependent O2 generation of neutrophils derived from
      the healthy human peripheral circulation (HPMNs) and the umbilical cord (UCBNs).
      METHODS: O2- generation and VE content were assayed by reduction of
      ferricytochrome c and by HPLC with an electrochemical detector, respectively.
      Neutrophil-specific annexin protein was identified by an immunological method.
      RESULTS: Both types of neutrophils generate significant amounts of PKC-dependent
      O2-generation, but weak PKC-independent O2-generation, except for opsonized
      zymosan-stimulated O2- generation in UCBNs. The VE content of UCBNs was similar
      to that of HPMNs although umbilical-cord blood contains a low concentration of
      VE. A neutrophil-specific annexin protein was also found in the UCBNs.
      CONCLUSION: UCBNs have a greater ability to incorporate VE than HPMNs do, but
      have similar general characteristics of stimulation-dependent O2-generation to
      those of HPMNs.

PMID- 8987336
TI  - Cytokines concentrations in the cervical mucus of pregnant women.
AB  - OBJECTIVE: Interleukin-1 alpha, interleukin-1 beta, interleukin-6 and interleukin
      8 in specimens of cervical mucus were assayed to assess defense mechanisms
      against infection in the cervical canal during pregnancy. METHODS: Two hundred
      and thirty-nine pregnant women who attended the obstetrics outpatient clinic in
      our hospital were included as subjects. Cervical mucus was collected with a newly
      developed collection swab, and cytokines and granulocyte elastase in the samples
      of cervical mucus were quantified using enzyme immunoassay kits. The 1-factor
      ANOVA, the Kruskal-Wallis test, and scheffe's F were used for statistical
      analysis. RESULTS: Interleukin-1 alpha, interleukin-1 beta and interleukin-8
      levels rose significantly as the concentrations of granulocyte elastase
      increased. High concentrations of interleukin-1 alpha (75.36 +/- 19.93 pg/ml),
      interleukin-1 beta (1005.29 +/- 238.75 pg/ml) and interleukin-8 (4822.4 +/- 633.2
      pg/ml) were found in the specimens from the group of high granulocyte elastase
      levels. CONCLUSIONS: These cytokines might be involved in defense mechanisms
      against ascending infection from the vagina.

PMID- 8987337
TI  - Raising food hygiene standards--could customer power and the new laws hold the
      key?
AB  - In September 1995 new general food hygiene regulations came into force. The new
      law, quite rightly, requires proprietors of food businesses to focus their
      thoughts and actions on risks to food safety. Proprietors are required to
      identify and assess risks and ensure that adequate management procedures are put
      into place to ensure food safety. This is a welcome move as contributing factors
      in most cases of food poisoning involve poor food hygiene practices. At the same
      time there has been a large increase in the amount of advice and guidance to
      local authority enforcement officers, particularly to assess risks to food safety
      when considering what action to take in any situation - the lower the risk the
      less appropriate it is to take legal action. However, there are many conditions
      found in food premises which present little or no risk to health, such as routine
      cleanliness in non-high risk areas, but lower standards on these might be viewed
      by the public as inappropriate for food businesses. With an increasing amount of
      choice available to customers, proprietors and managers of food businesses need
      to be more aware than ever of the complex pattern of consumer demands including
      that of supplying a clean and safe product in its broadest sense. The notion of
      consumer sovereignty is not a new concept. Combined with the new laws could it
      hold the key to genuine improved standards in food hygiene? This article reviews
      the subject and draws attention to a research programme being undertaken at the
      University of Brighton to identify, compare and contrast factors which the public
      perceive as important in terms of food hygiene in public eating places with those
      considered important by professionals with an interest in the subject. The
      results could bring benefits to the catering industry and customers.

PMID- 8987338
TI  - Latchkey children.
AB  - Children who are regularly left without adult supervision during a significant
      portion of the day, referred to as 'latchkey children', are a growing social
      phenomenon. The main reason for the rising prevalence of latchkey children is the
      increase in dual income and single parent families. Studies on the effects of the
      latchkey phenomenon report conflicting results. The potential positive
      consequences include learning to be independent and responsible. The potential
      negative consequences include loneliness, boredom, fear, academic under
      achievement, drug and alcohol abuse, accidental injury, and impairment of the
      parent-child relationship. Such wide variations in reported consequences in
      latchkey children might reflect differences in the maturity of the children and
      in the parent-child relationships prior to entering the latchkey arrangement.
      Counselling parents about the problems associated with a latchkey arrangement,
      referring children to an after-school programme, and teaching children self-help
      skills might minimise the possibility of negative consequences.

PMID- 8987339
TI  - Diet in the prevention of cancer: what are the chances of avoidance?
AB  - In most western populations, cancer causes about a fifth of all deaths, and in
      developing populations, 5-15%, with the likelihood of further rises. Diet is
      considered responsible for about a third of cases of cancer and smoking another
      third. Dietarily, for cancer avoidance, recommendations made include eat less,
      eat much less fat especially saturated fat, and eat more plant foods, i.e.
      cereals, but very particularly vegetables and fruit. However, only high
      consumptions of the latter are consistently associated with a lower risk of
      cancers, notably of the digestive and respiratory tracts. For each change urged,
      meaningful compliance will be very difficult, due largely to conservativeness as
      well as to the higher cost of a 'prudent' diet. Notwithstanding, urges to make
      dietary changes, particularly relating to plant foods, must be continued,
      especially with regard to persons familially susceptible and, additionally, with
      the recognition that the measures recommended also serve to lessen susceptibility
      to cardiovascular diseases. Compliance, even by a small proportion, could result
      in large numbers benefiting due to the universality of the burden from cancer.

PMID- 8987340
TI  - Tackling the tobacco challenge: achieving 'healthy public policy' in tobacco
      control in Guernsey.
AB  - Scientific evidence identifying smoking as the major cause of poor health and
      premature death in both industrialised and increasingly in developing countries
      is now overwhelming. Despite this, for a variety of reasons, there has been
      reluctance amongst many Governments including that of Britain, to take all
      logical action necessary to restrict and reduce smoking, especially amongst the
      young. The States of Guernsey in the Channel Islands has recently agreed to
      introduce an integrated package of measures designed specifically to make smoking
      less attractive and less accessible and less affordable to young people in an
      attempt to reduce the number of addicted adult smokers. These measures include a
      total ban of all public advertising of tobacco, apart from at point of sale, a
      substantial price rise followed by further price rises for a minimum period of
      five years, a raising of the minimum age for the purchase of tobacco from 16 to
      18 years, an increase in the size and content of pack health warnings, and
      increased funding for specific nonsmoking health promotion activities. The
      various barriers to achieving these reforms are described.

PMID- 8987341
TI  - Studies of risks associated with technological development in Nigeria.
AB  - This paper attempts to assess the magnitude of the risks associated with
      industrial and transportation technologies in Nigeria using data from various
      governmental agencies and private organisations. The minimum annual averages of
      injured persons and data from accidents associated with technological risks in
      Nigeria were as follows: factories-402.4 injured persons and 5.8 deaths;
      petroleum industry - 106.5 injured and 45.3 deaths; road traffic accidents -
      25,262 injured persons and 9,117 deaths; and railways 170.5 injured persons and
      43.2 deaths. Of the eleven plane crashes reported between 1978 and 1991 the nine
      crashes for which information was disclosed claimed 352 lives. The highest
      technological risk is from road traffic accidents. The annual average death from
      road traffic accidents (9,117) was 1.05 times the annual average death (8,662)
      from communicable diseases and 1.2 times the number of deaths (7,711) from
      cholera epidemics in 1991. Between 1988 and 1991 there were 855 reported cases of
      occupational diseases with an annual average of 214 cases. Conjunctivitis,
      dermatitis, chronic bronchitis and bronchial asthma accounted for 91% of the 855
      reported cases. The observations reflect the technological risk situation in
      Nigeria, and the need for improvements in both reducing risks and increasing the
      recording of risk statistics.

PMID- 8987344
TI  - Presentation to Senate Finance Committee Subcommittee on Health. Concerning
      Maryland Medicaid managed care program draft regulations.

PMID- 8987345
TI  - 1997 legislative prospectus.

PMID- 8987342
TI  - A survey of the adequacy of video display terminal/unit equipment in 7 local
      authorities in the Midlands.
AB  - In order to assess the adequacy of equipment in the run-up to the full
      implementation of the Display Screen Equipment Regulations, several local
      authorities agreed to take part in a pilot survey of their own video display
      terminals. The instrument was a self-reporting questionnaire based on the new
      regulations. A number of the questionnaires were also completed in parallel by
      EHOs in order to assess the objectivity with which questionnaires were completed.
      The surveys found many deficiencies but discovered that respondents with better
      levels of training were less critical of their work station. The reasons for this
      are discussed. The parallel inspection validated the instrument and suggests that
      self-inspection by users is a good indicator of some conditions at the work
      station but not of temperature, light, or relative humidity. Occupational stress
      was also measured. The levels were above UK average and levels of depression were
      found to be associated with respondents' aches and pains.

PMID- 8987349
TI  - Proposed fee schedule for physicians spells disaster for health care in Maryland.

PMID- 8987347
TI  - Wrap-up of 1996 legislative session--not just stadiums!

PMID- 8987350
TI  - Pulmonary tuberculosis in a high school student and a broad contact
      investigation: lessons relearned.
AB  - A case of acid-fast bacillus smear-positive cavitary tuberculosis (TB) was
      diagnosed in a high school senior (Student A) who lived in a community with a low
      prevalence for TB. A broad TB investigation was conducted in July 1994 among
      persons who attended the high school graduation with Student A. Follow-up
      investigations three months later focused on close contacts at highest risk. A
      positive tuberculin skin test (TST) was defined as induration of > or = 5 mm
      after placement of purified protein derivative. We determined the TST results and
      the estimated costs incurred by the local health department for the broad
      screening that was conducted. TST results were available for 122/161 (75%) close
      contacts, and for 1804 persons with nonclose contact with Student A. Her family
      members were known to have had prior positive TSTs. Positive TSTs were found
      among 3/122 (2.5%) close contacts, versus 34/1804 (1.9%) persons with nonclose
      contact. Only one close contact had conversion of TST from negative to positive,
      and no other active TB case was identified. We estimate the broad TST screening
      cost the local health department $36,507. Broad TST screening was costly and
      diverted staff from their customary public health service priorities. Local
      health departments and clinicians should follow the recommendations of the
      American Thoracic Society and the Centers for Disease Control and Prevention
      regarding TB contact investigations.

PMID- 8987351
TI  - Isolated systolic hypertension in the elderly.

PMID- 8987352
TI  - Maryland women living with HIV/AIDS.
AB  - Approximately one-quarter of the acquired immunodeficiency syndrome (AIDS) cases
      reported in Maryland are women. African-American women account for 80% or more of
      the cases in the Baltimore-Metropolitan area. Human immunodeficiency virus (HIV)
      positive women are frequently dealing with a constellation of social problems
      including lack of resources, care-taking responsibilities for extended families,
      histories of substance abuse, and loss of others to AIDS. This article is an
      attempt to describe the social context of living with HIV/AIDS to Maryland
      physicians.

PMID- 8987353
TI  - The Finneys of Baltimore: and the trumpets sounded.

PMID- 8987354
TI  - Acute leukemia and chemotherapy: a modeling viewpoint.
AB  - A couple of models of acute myeloblastic leukemia (AML) are proposed. Normal and
      leukemic cells are assumed to exist side-by-side with the two cell populations
      obeying Gompertzian dynamics but with the leukemic cells exercising inhibition
      over the normal cells. The kinetic equations and steady-state properties of one
      of the models is analytically obtained. Possible situations of detection or
      nondetection of malignancy are then discussed. Based on the models of AML, a
      treatment model is proposed and numerically simulated. Consequently, the option
      of aggressive treatment of the disease with heavy doses of drugs is shown to be a
      plausible and worthwhile chemotherapeutic strategy.

PMID- 8987355
TI  - Dynamical complexity in age-structured models of the transmission of the measles
      virus: epidemiological implications at high levels of vaccine uptake.
AB  - This article explores the effect of increasingly finely stratified age structure
      on the dynamical properties of deterministic metapopulation models of the
      transmission of the measles virus. The dynamical simplicity of earlier age
      structured models is shown to break down once the age-specific force of infection
      is no longer assumed to be constant across all child age classes below 5 years of
      age. While the biennial epidemics characteristic of earlier models are still
      observed, additional higher period stable cycles arise and coexist with the
      biennial cycle. The existence of multiple stable limit cycles necessarily implies
      model sensitivity on initial conditions, and for certain parameter values,
      chaotic dynamics are observed. Using a novel parameterization of the magnitude of
      seasonal forcing we are also able to make more biologically relevant comparisons
      between the dynamics of age- and non-age-structured models than have hitherto
      been possible. The epidemiological significance of these results is discussed,
      and we demonstrate that perturbations of the kind produced by intensive
      vaccination programs can shift transmission dynamics between biennial and
      triennial cycles. The possible implications of this work for studies of
      intermittency and infection persistence are also considered.

PMID- 8987356
TI  - Dose timing in tumor radiotherapy: considerations of cell number stochasticity.
AB  - A typical tumor radiotherapy regimen using external beam X rays consists of doses
      on weekdays for 4-7 weeks. During the final weeks, the tumor may contain only a
      few cells capable of regenerating the tumor and may be growing exponentially
      between doses. Stochastic fluctuations of the cell number can influence the
      optimal time pattern of dose delivery. If the total dose is fixed, a
      deterministic model of exponential tumor growth, neglecting stochastic effects,
      predicts that the way the radiation dose is spread out in time does not affect
      the average number of tumor cells at the end. However, we here show, within the
      framework of a birth-death model, that when stochastics are taken into account,
      the earlier the dose is given (consistent with other constraints imposed by quite
      different considerations), the better. The proof uses a transformation that
      simplifies the characteristic equation of the partial differential equation
      governing the probability generating function for a birth-death process with time
      dependent rates. The theorem that earlier is better holds for any statistical
      distribution of cell number from patient to patient at the start of the
      exponential growth phase and for virtually any cell-killing model. Numerical
      results indicate the stochastic effects, although not dominant, are not
      negligible.

PMID- 8987358
TI  - Soil microorganisms as controllers of atmospheric trace gases (H2, CO, CH4, OCS,
      N2O, and NO).
AB  - Production and consumption processes in soils contribute to the global cycles of
      many trace gases (CH4, CO, OCS, H2, N2O, and NO) that are relevant for
      atmospheric chemistry and climate. Soil microbial processes contribute
      substantially to the budgets of atmospheric trace gases. The flux of trace gases
      between soil and atmosphere is usually the result of simultaneously operating
      production and consumption processes in soil: The relevant processes are not yet
      proven with absolute certainty, but the following are likely for trace gas
      consumption: H2 oxidation by abiontic soil enzymes; CO cooxidation by the
      ammonium monooxygenase of nitrifying bacteria; CH4 oxidation by unknown
      methanotrophic bacteria that utilize CH4 for growth; OCS hydrolysis by bacteria
      containing carbonic anhydrase; N2O reduction to N2 by denitrifying bacteria; NO
      consumption by either reduction to N2O in denitrifiers or oxidation to nitrate in
      heterotrophic bacteria. Wetland soils, in contrast to upland soils are generally
      anoxic and thus support the production of trace gases (H2, CO, CH4, N2O, and NO)
      by anaerobic bacteria such as fermenters, methanogens, acetogens, sulfate
      reducers, and denitrifiers. Methane is the dominant gaseous product of anaerobic
      degradation of organic matter and is released into the atmosphere, whereas the
      other trace gases are only intermediates, which are mostly cycled within the
      anoxic habitat. A significant percentage of the produced methane is oxidized by
      methanotrophic bacteria at anoxic-oxic interfaces such as the soil surface and
      the root surface of aquatic plants that serve as conduits for O2 transport into
      and CH4 transport out of the wetland soils. The dominant production processes in
      upland soils are different from those in wetland soils and include H2 production
      by biological N2 fixation, CO production by chemical decomposition of soil
      organic matter, and NO and N2O production by nitrification and denitrification.
      The processes responsible for CH4 production in upland soils are completely
      unclear, as are the OCS production processes in general. A problem for future
      research is the attribution of trace gas metabolic processes not only to
      functional groups of microorganisms but also to particular taxa. Thus, it is
      completely unclear how important microbial diversity is for the control of trace
      gas flux at the ecosystem level. However, different microbial communities may be
      part of the reason for differences in trace gas metabolism, e.g., effects of
      nitrogen fertilizers on CH4 uptake by soil; decrease of CH4 production with
      decreasing temperature; or different rates and modes of NO and N2O production in
      different soils and under different conditions.

PMID- 8987357
TI  - Proton-dependent multidrug efflux systems.
AB  - Multidrug efflux systems display the ability to transport a variety of
      structurally unrelated drugs from a cell and consequently are capable of
      conferring resistance to a diverse range of chemotherapeutic agents. This review
      examines multidrug efflux systems which use the proton motive force to drive drug
      transport. These proteins are likely to operate as multidrug/proton antiporters
      and have been identified in both prokaryotes and eukaryotes. Such proton
      dependent multidrug efflux proteins belong to three distinct families or
      superfamilies of transport proteins: the major facilitator superfamily (MFS), the
      small multidrug resistance (SMR) family, and the resistance/ nodulation/cell
      division (RND) family. The MFS consists of symporters, antiporters, and
      uniporters with either 12 or 14 transmembrane-spanning segments (TMS), and we
      show that within the MFS, three separate families include various
      multidrug/proton antiport proteins. The SMR family consists of proteins with four
      TMS, and the multidrug efflux proteins within this family are the smallest known
      secondary transporters. The RND family consists of 12-TMS transport proteins and
      includes a number of multidrug efflux proteins with particularly broad substrate
      specificity. In gram-negative bacteria, some multidrug efflux systems require two
      auxiliary constituents, which might enable drug transport to occur across both
      membranes of the cell envelope. These auxiliary constituents belong to the
      membrane fusion protein and the outer membrane factor families, respectively.
      This review examines in detail each of the characterized proton-linked multidrug
      efflux systems. The molecular basis of the broad substrate specificity of these
      transporters is discussed. The surprisingly wide distribution of multidrug efflux
      systems and their multiplicity in single organisms, with Escherichia coli, for
      instance, possessing at least nine proton-dependent multidrug efflux systems with
      overlapping specificities, is examined. We also discuss whether the normal
      physiological role of the multidrug efflux systems is to protect the cell from
      toxic compounds or whether they fulfil primary functions unrelated to drug
      resistance and only efflux multiple drugs fortuitously or opportunistically.

PMID- 8987364
TI  - [Ischemic neuronal damage in early recovery. A morphological study on evolution
      of damage in hyperglycemia and normoglycemia].
AB  - The evolution of neuronal damage in various regions during ischemia and in early
      recovery was investigated morphologically using hyperglycemic and normoglycemic
      Wistar rats. Hyperglycemia (20-35 mu mol/ml plasma) was achieved with the
      infusion of glucose (i.v.) prior to ischemia. Forebrain ischemia (10 minutes) was
      induced by bilateral common carotid artery occlusion and hypotension.
      Normoglycemic rats were fasted prior to ishcemia. Ischemic changes of neurons
      were quantified by a five-point scale in the caudoputamen (CPu), globus pallidus
      (GP), hippocampus CA 1 (CA 1), parietal cortex (Par), and substantia nigra
      reticulata (SNR) during ishcemia and for 90 minutes after recirculation. In the
      hyperglycemic group, (1), CPu, CA 1 and Par; severely damaged neurons were seen
      at 60-90 minutes after recirculation. (2) GP; there was little neuronal damage.
      (3) SNR; immediately after recirculation damaged neurons were observed, and more
      damage was observed at 90 minutes post recirculation. In the normoglycemic group,
      no prominent neuronal damage was observed in any region. Hyperglycemia
      exacerbated ischemic neuronal damage after reperfusion. The evolution of neuronal
      damage was similar in the CPu and Par regions, but was different in the GP and
      SNR regions.

PMID- 8987363
TI  - [Purification and partial characterization of a novel human platelet aggregation
      factor in the extracellular products of Streptococcus mitis, strain Nm-65].
AB  - In this paper, we report the purification and partial characterization of human
      platelet aggregation factor form the extracellular products (ECP) of
      Streptococcus mitis (S. mitis) isolated from a patient with Kawasaki disease
      (KD). Platelet aggregation reaction was carried out using platelet-rich plasma
      (PRP) and washed platelets suspended in ACD-PBS. The aggregation factor was
      designated as S. mitis-derived human platelet aggregation factor (Sm-hPAF). The
      results obtained were as follows. 1) Sm-hPAF was isolated by chromatography on
      DEAE-Sepharose CL-6 B, hydroxyapatite and Superdex 75 columns. The purified Sm
      hPAF showed a single band upon SDS-polyacrylamide gel electrophoresis (SDS-PAGE)
      and molecular weight of approximately 66 kDa on SDS-PAGE. The isoelectric point
      (pI) of Sm-hPAF was 8.5, and Sm-hPAF showed an absorption peak at 278 nm on
      absorption spectra. When the platelet aggregation activity of the Sm-hPAF was
      compared with that of ECP, the specific aggregation activity of the of Sm-hPAF
      was significantly increased (up to 28-fold). Sugars were not found in Sm-hPAF.
      The sequence of the first 15 amino-terminal amino acid residues were H.Asp-Glu
      Gln-Gly-Asn-Arg-Pro-Val-Glu-Thr-Glu-Asn-Ile-Ala-Arg. The platelet aggregation
      activity of Sm-hPAF was inactivated by heating at 45 degrees C for 10 min. 2)
      PGE2 was released from platelets after incubation for 10 min with Sm-hPAF in a
      dose-dependent fashion. Platelet aggregation by the Sm-hPAF was totally inhibited
      by either PGE1, or GRGDS, but these reagents did not inhibit the platelet
      aggregation by collagen. 3) Histological examination of the rabbit skin sites
      showing an early reaction revealed increased dilatation of the veins and
      capillaries with cellular infiltration in the perivascular space of the dermis.
      Hyperplasia of the endothelial cells was noted. Degeneration of the vascular
      walls was observed in the later stages of the reaction. Aggregation of red cells
      in the vascular endothelium was also observed. Sm-hPAF was capable of producing
      vasculitis. 4) Twenty (76.9%) platelet-rich plasma samples (PRP) derived from 26
      healthy human volunteers reacted with Sm-hPAF, but the remaining 6 PRPs were not
      reactive. Preliminary study suggests the existence of an inhibitory factor in
      plasma from nonreactive donors.

PMID- 8987365
TI  - [Chronotropic effects of alpha-agonist on the rat isolated right atria].
AB  - This study was performed to investigate whether or not alpha-adrenergic
      stimulation exerts a chronotropic effect on the heart. Isolated right atria of
      rats were used. Phenylephrine (10(-5)-10(-4) mol/l), an alpha-agonist, did not
      affect the rate of the atrial beat under treatment with propranolol (1 x 10(-6)
      mol/l), a beta-blocker. When the atrial rate was increased to approximately
      double by treatment with isoproterenol (1 x 10(-8) mol/l) or forskolin (1 x 10(
      6) mol/l), phenylephrine at the same doses significantly reduced the rate by
      about 6%. This effect was blocked by phentolamine (1 x 10(-6) mol/l). These
      results suggest that alpha-adrenoceptors function to reduce heart rate in the
      atria, of which rate is raised through intracellular cAMP activity.

PMID- 8987362
TI  - [Mass screening of urinary tract infection for elementary and junior high school
      children].

PMID- 8987366
TI  - [Detection of ventricular late potentials and the incidence of ventricular
      tachycardia in diabetic patients, with reference to myocardial infarction].
AB  - To clarify the relationship between diabetes mellitus (DM) and fatal ventricular
      arrhythmias, such as ventricular tachycardia (VT), in patients with ishcemic
      heart disease, signal-averaged electrocardiograms were recorded in 107 patients
      with DM and/or myocardial infarction (MI). During the acute stage of MI (within 6
      weeks of onset), patients with DM had significantly greater amplitude in the last
      40 msec of filtered QRS as compared to those without DM (69.1 +/- 55.1 vs 33.9 +/
      17.5 microV, p < 0.01), thus signifying a lower incidence of late ventricular
      potential (LP) and VT. We therefore investigated the incidence of VT in 257
      consecutive patients with acute MI (74 with DM, 183 without DM). Although there
      was no significant difference in the incidence of VT between the two groups, a
      subgroup with congestive heart failure (CHF, Killip > or = II) in the DM group
      had a significantly lower incidence of VT than a subgroup with CHF but not DM
      (18.5% vs 41.9%, p < 0.05). It is concluded that patients with DM have a lower
      incidence of LP and VT during the acute stage of MI.

PMID- 8987367
TI  - [Virtual CT endoscopy "cruising eye view". Development and clinical
      applications].

PMID- 8987368
TI  - [Intraoperative diagnosis. The reason of restricted indication and suggestion].

PMID- 8987369
TI  - A new radiographic projection for the posterolateral notch in cases of recurrent
      dislocation of the shoulder.

PMID- 8987370
TI  - Low levels of IL-1ra versus IL-1 levels in prostatic fluid are not a cause of
      prolongation of prostatitis.

PMID- 8987371
TI  - Emergency response to environmental toxic incidents: the role of the occupational
      physician.
AB  - A survey of accidental environmental releases of hazardous chemicals conducted by
      the Agency for Toxic Substances and Disease Registry indicates that fixed
      facility events accounted for 77% of the episodes whereas 23% of the releases
      were related to transportation activities, such as loading or unloading
      materials. In nearly all the events (88%) only one chemical was released.
      Volatile organic compounds, chlorine, herbicides, acids and ammonia were the most
      common substances involved. In nearly one out of six reported events, an injury
      occurred. To prepare for emergencies associated with the accidental release of
      hazardous materials, the federal government, industry and professional
      organizations including the medical community have all been involved. In the
      United States, the Superfund Amendment Reauthorization Act (SARA) Title III
      passed in 1986 addresses the need to establish local emergency planning
      committees, to report and collect data, and a number of other matters.
      Professional societies, including the Joint Commission for the Accreditation of
      Health Care Organizations, the American College of Occupational and Environmental
      Medicine (ACOEM), and the American Industrial Hygiene Association, have all
      attempted to ensure proper education and training of those professionals called
      to assist in such emergencies. The occupational physician can assume numerous
      roles in the challenge related to emergency response, by becoming familiar with
      computerized information available to promptly determine the type of hazard
      released and its appropriate antidote, advising on the proper personal protective
      equipment, awareness of secondary contamination and participation on local
      emergency planning committees among many others. Emergency release of hazardous
      materials continues to occur with a frequency in the United States that deserves
      active vigilance and planning.

PMID- 8987372
TI  - Ill health retirement--guidelines for occupational physicians. Association of
      Local Authority Medical Advisors (working party).
AB  - These guidelines have been produced by a working party of the Association of
      Local Authority Medical Advisors to help doctors arrive at equitable decisions
      when assessing applications for ill health retirement. The general guidelines are
      intended to apply to all pension schemes and the specific ones to those such as
      The Local Government Pension Scheme where there is a requirement for the
      applicant to have permanent ill health.

PMID- 8987373
TI  - Work-related musculoskeletal symptoms among car mechanics: a descriptive study.
AB  - A questionnaire concerning musculoskeletal symptoms (MSS) and working environment
      was answered by 100% of 103 car mechanics in 12 different garages. Almost all the
      mechanics had been troubled with MSS at work the past year. The most common MSS
      were symptoms from the low back, neck, head and shoulders. When asked which
      symptoms had been most troublesome at work most mechanics reported symptoms from
      the low back, upper back, shoulders and neck. Symptoms from the shoulders, low
      back and upper back were associated with absence from work due to MSS (OR = 4.2,
      2.3 and 2.1 respectively). Mechanics between the ages of 30 and 40 reported
      significantly more shoulder symptoms than both younger and older colleagues (p <
      0.001). It seems that symptoms from the back and shoulders restrain car
      mechanics, work more than any other MSS. The mechanics' most common working
      postures may contribute to the development of back and shoulder symptoms.

PMID- 8987374
TI  - Work related injuries in Danish fishermen.
AB  - A one-year retrospective study among Danish commercial fishermen revealed that
      the overall rate of injury was 20.4 per 100 persons per year. There were no
      significant differences in injury rates related to age. The overall rates of
      injury related to the different types of vessels-trawlers, gill-netters and
      Danish seiners-did differ statistically when the number of man-days at sea was
      taken into account. There was, however, a significant increase in the number of
      injuries on trawlers over 100 gross register tons. The overall number of days
      lost due to injury among all fisherman was 47 days per 1,000 days at sea. The
      highest number of days lost for work was on trawlers of 100-199 gross register
      tonnage. Preventive measures should be implemented in all age groups and in all
      the main types of fishing vessels.

PMID- 8987360
TI  - The secretory pathway of protists: spatial and functional organization and
      evolution.
AB  - All cells secrete a diversity of macromolecules to modify their environment or to
      protect themselves. Eukaryotic cells have evolved a complex secretory pathway
      consisting of several membrane-bound compartments which contain specific sets of
      proteins. Experimental work on the secretory pathway has focused mainly on
      mammalian cell lines or on yeasts. Now, some general principles of the secretory
      pathway have become clear, and most components of the secretory pathway are
      conserved between yeast cells and mammalian cells. However, the structure and
      function of the secretory system in protists have been less extensively studied.
      In this review, we summarize the current knowledge about the secretory pathway of
      five different groups of protists: Giardia lamblia, one of the earliest lines of
      eukaryotic evolution, kinetoplastids, the slime mold Dictyostelium discoideum,
      and two lineages within the "crown" of eukaryotic cell evolution, the alveolates
      (ciliates and Plasmodium species) and the green algae. Comparison of these
      systems with the mammalian and yeast system shows that most elements of the
      secretory pathway were presumably present in the earliest eukaryotic organisms.
      However, one element of the secretory pathway shows considerable variation: the
      presence of a Golgi stack and the number of cisternae within a stack. We suggest
      that the functional separation of the plasma membrane from the nucleus
      endoplasmic reticulum system during evolution required a sorting compartment,
      which became the Golgi apparatus. Once a Golgi apparatus was established, it was
      adapted to the various needs of the different organisms.

PMID- 8987375
TI  - Reasons for rejection: why people fail to qualify as firefighters.
AB  - In the decade beginning 1 January 1985, 916 individuals (including five females)
      were medically examined with a view to joining the full-time service of
      Strathclyde Fire Brigade (SFB). One hundred and nine (11.9%), including two
      females, were rejected. The five main causes of failure were: ocular (n = 46,
      42.2%); lack of stamina (n = 21, 19.2%); 'others' (n = 12, 11.0%); cardiovascular
      (n = 9, 8.3%) and orthopaedic (n = 6, 5.5%). Thirty-two had chest X-rays. One
      abnormality was found -an azygous lobe-but it played no part in the decision to
      decline the applicant. There was little life- or health-threatening pathology
      found. The most serious cases were murmurs consistent with mitral stenosis and
      regurgitation (one each), one case of ocular melanoma, four cases of hypertension
      and two cases of haematuria/ proteinuria (++). This study shows that potentially
      serious findings can occasionally be detected in a population of 18-30 year olds
      who might be expected to be of better than average fitness, and that routine
      chest X-rays are not helpful in the selection process.

PMID- 8987376
TI  - Musculoskeletal problems in the tomato growing industry: 'tomato trainer's
      shoulder'?
AB  - Tomato training entails highly repetitive shoulder muscle contractions, static
      contractions and work at shoulder level, factors linked in other working groups
      with neck and shoulder complaints. The frequency of musculoskeletal complaints
      was compared using the Nordic Questionnaire in 56 tomato trainers and 52 other
      matched glasshouse workers whose job did not include these work task factors. A
      higher 12- month (odds ratio (OR) = 5.9; [95% confidence interval (CI) = 2.4
      16.7] and 7- day (OR = 3.6, CI = 1.2-11.1) period prevalence of shoulder
      complaint was recorded in trainers than in pickers and deleafers. Other upper
      limb and upper trunk complaints were also more common in tomato trainers,
      highlighting an area of ergonomic concern.

PMID- 8987377
TI  - A survey of respiratory and dermatological disease in the chrome plating industry
      in the West Midlands, UK.
AB  - Between 1993-1995 a cross-sectional survey of 20 chrome plating companies in the
      West Midlands was undertaken to assess the prevalence of respiratory and
      dermatological disease in platers. By means of a questionnaire and clinical
      examination 71 platers were examined of whom 23% were found to have dermatitis at
      the time of the visit and 45% of companies had at least one case of dermatitis in
      their plating workforce. Twenty-three per cent of platers had evidence of old
      chrome ulceration and 13% had evidence of new and healing chrome ulcers. When the
      nasal passages of platers were examined 17% had inflammation and 14% had septal
      perforation. Those with perforations were aged less than 35 years at the time of
      perforation which had usually occurred in the first 10 years of exposure. Lower
      respiratory symptoms were rare. Guidance on the prevention of disease in this
      occupational group which does not always have ready recourse to experienced
      occupational medical advice will be discussed.

PMID- 8987378
TI  - Upper limb disorders.
AB  - Disorders of the upper limb cause significant morbidity and incur substantial
      costs. These conditions are amongst the most common reasons for attendance to
      occupational physicians, and they are also commonly encountered in the practice
      of a wide array of medical specialities (rheumatology, orthopaedic surgery,
      rehabilitation and neurology). Despite this collective experience, standardized
      methods for labelling these conditions and algorithms for their clinical
      evaluation and treatment are only beginning to be developed. The purpose of this
      review is to outline a classification system for upper limb disorders, to address
      the features of the clinical history and examination which are of most benefit in
      reaching a diagnosis, and to briefly outline approaches to investigation and
      treatment.

PMID- 8987361
TI  - T helper cell activation and human retroviral pathogenesis.
AB  - T helper (Th) cells are of central importance in regulating many critical immune
      effector mechanisms. The profile of cytokines produced by Th cells correlates
      with the type of effector cells induced during the immune response to foreign
      antigen. Th1 cells induce the cell-mediated immune response, while Th2 cells
      drive antibody production. Th cells are the preferential targets of human
      retroviruses. Infections with human T-cell leukemia virus (HTLV) or human
      immunodeficiency virus (HIV) result in the expansion of Th cells by the action of
      HTLV (adult T-cell leukemia) or the progressive loss of T cells by the action of
      HIV (AIDS). Both retrovirus infections impart a high-level activation state in
      the host immune cells as well as systemically. However, diverging responses to
      this activation state have contrasting effects on the Th-cell population. In HIV
      infection, Th-cell loss has been attributed to several mechanisms, including a
      selective elimination of cells by apoptosis. The induction of apoptosis in HIV
      infection is complex, with many different pathways able to induce cell death. In
      contrast, infection of Th cells with HTLV-1 affords the cell a protective
      advantage against apoptosis. This advantage may allow the cell to escape immune
      surveillance, providing the opportunity for the development of Th-cell cancer. In
      this review, we will discuss the impact of Th-cell activation and general immune
      activation on human retrovirus expression with a focus upon Th-cell function and
      the progression to disease.

PMID- 8987379
TI  - How to write a recruiting policy.
AB  - Occupational health professionals have an important role to play in ensuring that
      individuals recruited by any organization are medically capable of performing
      their required duties in an efficient manner. To achieve this, the physician's
      knowledge of the workplace should be used to establish the necessary medical
      standards whilst their occupational health expertise and experience should be
      called upon to establish the relevant means of objectively assessing attainment
      of the established criteria. A written policy detailing the procedures, both
      medical and administrative is essential.

PMID- 8987380
TI  - Hydration in protein crystallography.
AB  - Water in close proximity to the protein surface is fundamental to protein
      folding, stability, recognition and activity. Protein structures studied by
      diffraction methods show ordered water molecules around some charged, polar, and
      non-polar (hydrophobic) amino acids, although the later are only observed when
      they are at the interface between symmetry related molecules in the crystal.
      Water networks surrounding the protein have been observed for small proteins.
      Crystallographically observed water molecules are referred to as bound structural
      water molecules. During crystallographic data analysis, bound water molecules are
      often treated as though they belong to the protein. Recent developments in the
      treatment of the bulk solvent contribution to the low order diffraction data
      allow a better evaluation of the surface structure of the protein and a better
      localization of bound waters. The mobility of bound waters is studied by means of
      temperature and occupancy factors. The bulk solvent has relatively large disorder
      (liquid like) which is represented by liquidity factors. Within this context
      water layers surrounding the protein have little mobility.

PMID- 8987382
TI  - Protein-protein recognition.

PMID- 8987381
TI  - Circular permutation of polypeptide chains: implications for protein folding and
      stability.

PMID- 8987383
TI  - Application of the anomalous dispersion of X-rays to macromolecular
      crystallography.

PMID- 8987359
TI  - Flow cytometry and cell sorting of heterogeneous microbial populations: the
      importance of single-cell analyses.
AB  - The most fundamental questions such as whether a cell is alive, in the sense of
      being able to divide or to form a colony, may sometimes be very hard to answer,
      since even axenic microbial cultures are extremely heterogeneous. Analyses that
      seek to correlate such things as viability, which is a property of an individual
      cell, with macroscopic measurements of culture variables such as ATP content,
      respiratory activity, and so on, must inevitably fail. It is therefore necessary
      to make physiological measurements on individual cells. Flow cytometry is such a
      technique, which allows one to analyze cells rapidly and individually and permits
      the quantitative analysis of microbial heterogeneity. It therefore offers many
      advantages over conventional measurements for both routine and more exploratory
      analyses of microbial properties. While the technique has been widely applied to
      the study of mammalian cells, is use in microbiology has until recently been much
      more limited, largely because of the smaller size of microbes and the
      consequently smaller optical signals obtainable from them. Since these technical
      barriers no longer hold, flow cytometry with appropriate stains has been used for
      the rapid discrimination and identification of microbial cells, for the rapid
      assessment of viability and of the heterogeneous distributions of a wealth of
      other more detailed physiological properties, for the analysis of antimicrobial
      drug-cell interactions, and for the isolation of high-yielding strains of
      biotechnological interest. Flow cytometric analyses provide an abundance of
      multivariate data, and special methods have been devised to exploit these.
      Ongoing advances mean that modern flow cytometers may now be used by
      nonspecialists to effect a renaissance in our understanding of microbial
      heterogeneity.

PMID- 8987384
TI  - From conductances to neural network properties: analysis of simple circuits using
      the hybrid network method.

PMID- 8987385
TI  - Structure and function of the phosphotyrosine binding (PTB) domain.

PMID- 8987386
TI  - A framework for the analysis of mixed time series/point process data--theory and
      application to the study of physiological tremor, single motor unit discharges
      and electromyograms.

PMID- 8987387
TI  - Know your practice inside & out.

PMID- 8987388
TI  - Did socioeconomic factors influence clinical decisions?

PMID- 8987389
TI  - Department of Justice and FTC redefine antitrust rules.

PMID- 8987391
TI  - Newborn screening in Tennessee.

PMID- 8987390
TI  - Recognizing Weber-Christian disease.
AB  - The eponym Weber-Christian Disease (WCD) defines a chronic disorder characterized
      by relapsing febrile episodes and panniculitis. Systemic manifestations due to
      visceral involvement may be present. WCD is associated with no identifiable
      cause, although chronic panniculitis may be due to definable underlying
      disorders. A variety of distinctive disease entities, such as systemic lupus
      erythematosus (SLE), pancreatic disease, alpha-I-antitrypsin disease,
      lymphoproliferative neoplasia, infections, or trauma are associated with chronic
      panniculitis. The accurate diagnosis of panniculitis requires an adequate deep
      skin biopsy showing inflammation of the subcutaneous layers. We describe a white
      woman with fever and recurrent episodes of painful nodules of the lower
      extremities, excisional biopsy of which confirmed panniculitis. The febrile
      episodes and skin lesions responded dramatically with the use of oral
      corticosteroids.

PMID- 8987392
TI  - Acute stroke intervention.

PMID- 8987393
TI  - Molecular mechanisms of the protein serine/threonine phosphatases.
AB  - The dephosphorylation of proteins on their serine, threonine and tyrosine
      residues is catalysed by three families of protein phosphatases that regulate
      numerous intracellular processes. Diversity of structure within a family is
      generated by targeting and regulatory subunits and domains. Structural studies of
      these enzymes have revealed that although the two families of protein Ser/Thr
      phosphatases are unrelated in sequence, the architecture of their catalytic
      domains is remarkably similar and distinct from the protein tyrosine
      phosphatases. Insights into the molecular mechanisms of catalysis and regulation
      of these enzymes have been obtained.

PMID- 8987395
TI  - Three-part inventions: intracellular signaling and induced proximity.
AB  - Everyone has had the experience of stoking a fire; putting the logs close
      together causes flames to appear from previously dying embers. In a similar way,
      mere proximity might mediate qualitative biological responses. We discuss natural
      molecules that appear to have arisen to bring two proteins together and
      illustrate how this simple mechanism can be used to control a wide variety of
      biological processes.

PMID- 8987394
TI  - Structure and function of the protein tyrosine phosphatases.
AB  - The tyrosine and dual-specificity phosphatases are involved in signaling, cell
      growth and differentiation, and the cell cycle. The enzymes share a common
      catalytic mechanism mediated by an active site cysteine, arginine and aspartic
      acid. Supplementary domains assist in targeting and substrate specificity.

PMID- 8987396
TI  - A novel family of Ras-binding domains.

PMID- 8987397
TI  - KOW: a novel motif linking a bacterial transcription factor with ribosomal
      proteins.

PMID- 8987399
TI  - Making sense of nonsense in yeast.
AB  - Messenger RNA (mRNA) degradation is a process that plays an important role in the
      regulation of gene expression and can be linked to translation. Study of the
      nonsense-mediated mRNA decay pathway has greatly aided our understanding of the
      link between these processes. Evidence indicates that this pathway regulates the
      abundance of both aberrant and wild-type transcripts. Factors involved in this
      pathway have been identified and recent results indicate that they might also be
      involved in modulating translation. Here, we discuss the mechanism of nonsense
      mediated mRNA decay in the yeast Saccharomyces cerevisiae and the potential role
      that this pathway can have on the regulation of gene expression.

PMID- 8987398
TI  - Functions for MHC class I carbohydrates inside and outside the cell.
AB  - Major histocompatibility complex (MHC) class I heavy chain glycoproteins have an
      invariant N-linked glycosylation site at Asn86, which is found between two
      extremely variable protein domains. For human MHC class I molecules, Asn is the
      only site of glycosylation and the attached oligosaccharides are remarkably
      uniform. The carbohydrate initiates interactions with calnexin in the endoplasmic
      reticulum that facilitate the assembly of MHC class I molecules and their
      delivery to the cell surface. However, recognition of MHC class I molecules by
      antibodies and T cells is indifferent to the carbohydrate, although lines of
      circumstantial evidence implicate lectins and carbohydrates in the recognition of
      MHC class I glycoproteins by natural killer cells.

PMID- 8987400
TI  - Evidence for a Ras/Ral signaling cascade.
AB  - It is becoming clear that Ras proteins mediate their diverse biological functions
      by binding to, and participating in, the activation of multiple downstream
      targets. Recent work has identified nucleotide-exchange factors for Ral-GTPases
      as the newest members of the set of putative Ras 'effector molecules'. This new
      work has also detected two potential downstream targets of Ral proteins, a novel
      CDC42/Rac GTPase-activating protein and a phospholipase D.

PMID- 8987401
TI  - Methods and reagents. Eliminating ghost bands from plasmid preps.
AB  - Methods and reagents is a unique monthly column that highlights current
      discussions in the newsgroup bionet.molbio.methds-reagnts, available on the
      internet. This month's column updates the discussion of a ghost DNA band that
      continues to haunt netters. For details on how to partake in the newsgroup, see
      the accompanying box.

PMID- 8987402
TI  - Eukaryotic gene nomenclature--a resolvable problem?

PMID- 8987403
TI  - Connecting protein family resources using the proWeb network.

PMID- 8987404
TI  - Lessons from the discovery of the ubiquitin system.

PMID- 8987405
TI  - Hepatic venous outflow obstruction--where east meets west.

PMID- 8987406
TI  - Aflatoxin and liver injury.

PMID- 8987407
TI  - Bacterial enterotoxins.

PMID- 8987408
TI  - Hepatic venous outflow obstruction in Nepal.
AB  - Intra hepatic inferior venacaval (IVC) obstruction at the site or just above
      hepatic vein opening in the IVC, is a common hepatic problem in Nepal. These
      patients either present as a chronic IVC obstruction with insidious onset or may
      present with rapid onset disease (acute/subacute disease). The former type may be
      asymptomatic (20%) or may have features of chronic liver dysfunction. The latter
      presents with rapid onset ascites. Presence of hepatomegaly with flank/back veins
      are characteristic clinical features of the disease. The disease is invariably
      encountered amongst rural poor, alcoholic and in the peripartum period.
      Ultrasonography, IVC graphy hepatogram and liver biopsies are the usual
      diagnostic modalities. Twenty four percent of the 126 chronic hepatic IVC disease
      had associated liver cell cancer at our centre. The aetiology of the disease is
      unclear. Presently it is believed that local thrombophlebitis in IVC causes such
      obstruction. Despite, surgical and radiological intervention, the ideal
      management in such patients is yet to be established. We believe conservative
      therapy, particularly prevention and early therapy of sepsis in such patients
      prolongs survival.

PMID- 8987409
TI  - Falciparum malaria with acute liver failure.
AB  - INTRODUCTION: Falciparum malaria occasionally presents with encephalopathy,
      jaundice and fever mimicking fulminant hepatic failure. PATIENTS: We recently
      managed seven cases (mean age 34 years, range 20-45; all men) of acute falciparum
      malaria presenting with a short history [mean duration 8.1 (4-15) days] of fever,
      jaundice, altered sensorium and oliguria. Only one patient had splenomegaly.
      Investigations revealed jaundice (bilirubin 1.9-30.7 mg/dl), moderate to severe
      anaemia (Hb 4-8 gm/dl), increased liver enzymes (2-4 times normal) and azotaemia
      (serum creatinine 1.6-7.4 mg/dl). Coagulation parameters were deranged in 3 with
      clinical bleeding in two cases. One patient without a past history of diabetes
      had increased blood glucose values with ketonuria. HBsAg was negative in all
      cases. Patients received supportive therapy along with intravenous quinine.
      Peritoneal dialysis was done in one patient. Three patients showed rapid recovery
      and four succumbed to the disease. Post-mortem liver biopsy showed Kupffer cell
      hyperplasia, pigment deposition, foci of steatosis and necrosis along with
      submassive necrosis in one case. CONCLUSIONS: In areas endemic for malaria,
      awareness of this entity is a must. In a patient with jaundice and altered
      sensorium, disproportionate anaemia, azotaemia and only mild elevation of liver
      enzymes should help differentiate these patients from cases of fulminant hepatic
      failure. The diagnosis can be confirmed by peripheral blood examination. Early
      institution of specific therapy may be the only life saving measure in these
      patients.

PMID- 8987410
TI  - Early gastric carcinoma.
AB  - This is a retrospective analysis of 8 cases of early gastric carcinoma treated
      from 1988 to 1995 in Bangalore. All the cases underwent surgery after being
      diagnosed by endoscopy and biopsy. One patient died of an unrelated cause 2 years
      after surgery. The remaining 7 patients are asymptomatic and without recurrence.

PMID- 8987412
TI  - TCBS for the isolation of Vibrio cholerae.

PMID- 8987411
TI  - Primary biliary cirrhosis without pruritus--an Indian variant.
AB  - Primary biliary cirrhosis (PBC) is extremely rare in India. We report three cases
      of PBC without pruritus. The absence of pruritus in the present cases and in
      those reported earlier from India is highlighted.

PMID- 8987414
TI  - Percutaneous catheter drainage in pancreatic pseudocysts.
AB  - Percutaneous catheter drainage (PCD) was performed in 12 pancreatic pseudocysts
      in 11 patients. The procedure was performed under realtime ultrasound guidance
      adopting a direct transperitoneal approach in all cases. Complete cure was
      achieved in 9 (75%) of the Pseudocysts drained. Success rate was higher in
      pseudocysts not communicating with the main pancreatic duct (MPD), 7 of 8 (87.5%)
      as compared to those with ductal communication, 2 of 4 (50%). The mean duration
      of catheter drainage was 14.2 days in the first group while it was significantly
      longer, (42.5 days) in the latter group. No death or major complication related
      to the procedure was encountered in the study. A single pseudocyst got infected
      after catheter insertion but it was treated successfully with antibiotics. The
      follow up period was 3-18 months with a mean of 6.8 months. PCD failed in 2
      pseudocysts communicating with MPD and associated strictures in the MPD. In one
      case having no communication with MPD the procedure failed because the cyst had
      thick debris which could not be drained properly. PCD may be a safe and effective
      therapy in the management of pseudocysts with best results in those not
      communicating with the MPD. Communicating pseudocysts, also having strictures in
      MPD, should not be subjected to PCD.

PMID- 8987413
TI  - Non-surgical treatment of achalasia cardia.

PMID- 8987415
TI  - Impact of the site of arterial anastomosis on the risk of biliary complications
      after liver transplantation.
AB  - Biliary complications are an important cause of morbidity after orthotopic liver
      transplantation (OLT). It has been suggested that the denervation of recipient
      bile duct and the sphincter of Oddi may contribute to biliary complications.
      Recipient bile duct and the sphincter of Oddi receive its regulatory innervation
      through the nerve plexus around the gastroduodenal artery (GDA). These nerves are
      likely to be severed if recipient hepatic artery is divided at or proximal to the
      origin of GDA during arterial anastomosis of OLT (proximal arterial anastomosis).
      This study was carried out to determine the impact of the site of arterial
      anastomosis on the incidence of biliary complications. A total of 331 transplants
      by a single surgeon (JACB) were analysed. Patients with Roux-en-Y
      choledochoduodenostomy were excluded. Biliary complications were noted in 16.9%
      patients during first three months after transplantation. Incidence of biliary
      complications in patients with proximal and distal arterial anastomosis was found
      to be 17.2% and 12.9% respectively (ns). We conclude that the site of arterial
      anastomosis as an index of sphincter of Oddi denervation does not significantly
      influence the incidence of biliary complications.

PMID- 8987416
TI  - Anal leiomyosarcoma.

PMID- 8987417
TI  - Hepatitis B vaccination in the expanded programme of immunization.

PMID- 8987418
TI  - Hepatitis B--potential of perinatal transmission in India.
AB  - To estimate the frequency of perinatal hepatitis B virus (HBV) infection, 850
      pregnant females were tested for HBsAg and HBeAg using RPHA kits. Frequency of
      HBsAg positivity was 4.6% by RPHA and 6.34% by micro-ELISA. HBeAg was detected in
      18% of the HBsAg positive pregnant females. Presuming a perinatal HBV infection
      rate of 90% amongst infants born to HBsAg and HBeAg positive pregnant females and
      17% amongst infant born to HBsAg positive but HBeAg negative mothers, we
      estimated that 1.17% to 1.64% infants out of 24 million births occurring annually
      in this country would be infected with HBV. In other words every year 2.8 to 3.9
      lakh infants are being infected by HBV perinatally, 90% of whom will eventually
      develop chronic HBV infection. Urgent control measures are necessary to
      circumvent this problem.

PMID- 8987420
TI  - Expanded programme on immunization (EPI). Decrease of measles cases in Mexico.

PMID- 8987419
TI  - Biennial meet of the International Association for the Study of the Liver. Cape
      Town, 18-24 February 1996.

PMID- 8987421
TI  - Zoonoses control 1995.

PMID- 8987422
TI  - Food safety. Outbreak of botulism.

PMID- 8987423
TI  - Surveillance of traumatic brain injuries in Utah.
AB  - From 1990 through 1992 we conducted surveillance of cases requiring hospital
      admission and of fatal cases of traumatic brain injury among residents of Utah
      and found an annual incidence rate of 108.8 per 100,000 population. The greatest
      number of injuries occurred among men and persons aged 15 to 24 years. Motor
      vehicles were the leading cause of injury, followed by falls and assaults. The
      incidence rate we found is substantially lower than previously published rates of
      traumatic brain injury. This may be the result of a decrease in the incidence of
      these injuries in the decade since earlier studies were done, as well as changing
      hospital admission criteria that serve to exclude less severe cases of injury.
      Despite the apparent decline in rates, our findings indicate the continued
      importance of traumatic brain injury as a public health problem and the need to
      develop more effective prevention strategies that will address the major causes
      of these injuries.

PMID- 8987424
TI  - Sputum gram's stain in community-acquired pneumococcal pneumonia. A meta
      analysis.
AB  - The usefulness of the sputum Gram's stain is controversial. This meta-analysis
      was designed to evaluate the sensitivity and specificity of the sputum Gram's
      stain in community-acquired pneumococcal pneumonia. Using a predetermined
      protocol, articles were discovered through a MEDLINE search (1966 to 1993) and
      the examination of bibliographies and were graded for quality by three blinded
      reviewers. Information on the reference standard, blinding, stain interpreter,
      control for antibiotic use, and definition of a positive test was collected. We
      found 12 articles containing 17 test characteristics to evaluate. The number of
      patients in each study ranged from 16 to 404. Sputum culture was the most common
      reference standard (10 of 17 estimations). Sensitivity ranged from 15% to 100%
      and specificity from 11% to 100%. Test characteristics varied markedly among
      studies and appeared related partly to the test interpreter. The sputum Gram's
      stain may yield misleading results in community-acquired pneumonia, as its
      sensitivity and specificity vary substantially in different settings. A
      practitioner electing to use the study should be well trained and use a specific
      definition for a positive test.

PMID- 8987425
TI  - When patients ask about assisted suicide. A viewpoint from Oregon.
AB  - The passage of the Oregon Death With Dignity Act has profound implications for
      the prevailing model of care for dying patients. Patients are already asking for
      assisted suicide. Most physicians have not been trained in evaluating these
      requests in a therapeutic way. We discuss the issues around the needs of dying
      patients and, regardless of the legal status, what to do when patients ask for a
      lethal dose of medication. With the tools to explore the meaning of these
      requests, physicians will be better able to understand and meet the needs of
      their dying patients.

PMID- 8987426
TI  - Practice environment for nurse practitioners in California. Identifying barriers.
AB  - Barriers exist that prevent nurse practitioners from using their primary health
      care knowledge and skills. We present the incidence of and specific barriers
      experienced by nurse practitioner respondents in California, the state with the
      largest number of nurse practitioners in the nation. A January 1995 survey was
      sent to all nurse practitioners certified in California to elicit their
      experiences regarding legal or social barriers in their practice, with space for
      an open-ended response. Of an estimated 3,895 nurse practitioners in California,
      2,741 (70%) returned surveys. Most nurse practitioner (65%) respondents in
      California are providing primary care. Perceived barriers to practice are lack of
      prescriptive authority, lack of support from physicians, reimbursement
      difficulties, and lack of public awareness. Current barriers to nurse
      practitioner practice in California are similar to national barriers discovered
      in 1992 data. The development of interprofessional dialogue and the recognition
      of the contributions of all primary care professionals are some of the steps that
      can be taken to reduce these barriers and increase the use and effectiveness of
      nurse practitioners in primary care.

PMID- 8987428
TI  - Epidemiology and control of coccidioidomycosis in California.

PMID- 8987427
TI  - Prognosis and treatment of burns.
AB  - Survival rates for burn patients in general have improved markedly over the past
      several decades. The development of topical antibiotic therapy for burn wounds,
      the institution of the practice of early excision and grafting, and major
      advances in intensive care management have all contributed to this success. In
      this review we address these 3 important advances in the modern treatment of burn
      injuries and provide a brief historical overview of these accomplishments and
      others, emphasizing specific achievements of note and promises for the future. We
      also discuss 3 topics of interest to burn physicians, including the special
      problems and high mortality of elderly burn patients, the disturbingly high
      mortality in burn patients with inhalation injury, and the possible use of
      artificial skin to facilitate rapid wound closure.

PMID- 8987429
TI  - Occupational lead exposure and management.

PMID- 8987430
TI  - Human babesiosis and ehrlichioses--emerging tick-borne diseases.

PMID- 8987431
TI  - Directly observed therapy for tuberculosis.

PMID- 8987432
TI  - Multidrug-resistant tuberculosis--how far are we from New York City?

PMID- 8987433
TI  - Smoking cessation--new challenge and opportunities.

PMID- 8987434
TI  - Naltrexone hydrochloride use in the treatment of alcoholism.

PMID- 8987435
TI  - Spontaneous group B streptococcal meningitis in a patient with cirrhosis.

PMID- 8987436
TI  - Lysinuric protein intolerance presenting as coma in a middle-aged man.

PMID- 8987437
TI  - Parkinson's disease. Diagnosis and treatment.
AB  - Although Parkinson's disease is primarily a neurologic disorder, primary care
      physicians should be knowledgeable about the disease and its treatment because
      most patients will see their primary care physician first for their symptoms.
      Furthermore, in today's setting of managed care, primary care physicians will
      likely be called on even more to assume primary responsibility for the treatment
      of patients afflicted with Parkinson's disease; neurologists will likely play the
      role of consultants who see a patient only periodically and offer recommendations
      and advice for the primary care physicians to implement.

PMID- 8987438
TI  - Academic physicians, clinical investigators, and managed care. Whither
      Hippocrates?

PMID- 8987439
TI  - Barriers to practice--reality or perception?

PMID- 8987440
TI  - Physicians and nurse practitioners--old conflicts and new opportunities.

PMID- 8987441
TI  - Parkinson's disease--a progress report.

PMID- 8987442
TI  - A guide of the perplexed--assisted suicide.

PMID- 8987443
TI  - Out-of-control snowboarders.

PMID- 8987444
TI  - Antagonistic effects of intestinal Lactobacillus isolates on pathogens of
      chicken.
AB  - Twelve Lactobacillus strains isolated from chicken intestine, which demonstrated
      a strong and moderate capacity to adhere to the ileal epithelial cells in vitro,
      were used to investigate their inhibitory ability against five strains of
      salmonella, i.e. Salmonella enteritidis 935/79, Salm. pullorum, Salm.
      typhimurium, Salm. blockley and Salm. enteritidis 94/448, and three serotypes of
      Escherichia coli, viz. E. coli O1:K1, O2:K1 and O78:K80. The results showed that
      all the 12 Lactobacillus isolates were able to inhibit the growth of the five
      strains of salmonella, and the three strains of E. coli in varying degrees.
      Generally, they were more effective in inhibiting the growth of salmonella than
      E. coli. Inhibition of the pathogenic bacteria was probably due to the production
      of organic acids by the Lactobacillus isolates.

PMID- 8987445
TI  - Identification of Rhodococcus equi using the polymerase chain reaction.
AB  - Two regions in the gene coding for 16S rRNA in Rhodococcus equi were selected as
      species-specific primer sequences for the polymerase chain reaction (PCR). PCR
      using these primers was tested against 10 strains of R. equi (including the type
      strain) and gave positive results for all but was negative for all other tested
      species of Rhodococcus; representatives of the most closely related genera and a
      number of other bacterial species. This method could therefore be used to
      identify this species which can infect the lungs or other organs of horses, pigs,
      humans and other animals.

PMID- 8987447
TI  - Fatty acid patterns of film-forming yeasts and new evidence for the heterogeneity
      of Pichia membranaefaciens.
AB  - Total fatty acids (C14:0 to C18:3) of 50 strains assigned by classical
      identification methods to Pichia membranaefaciens (28), P. anomala (15), Dekkera
      anomala (2), D. bruxellensis (2) and Candida vini (3) were determined and data
      analysed by multivariate statistical procedures. Principal components cluster
      analysis defined six groups of strains. Thirteen strains of P. anomala formed a
      well-defined cluster, whereas P. membranaefaciens was split into three groups.
      The taxonomic status of the P. membranaefaciens strains was evaluated by
      determination of the G + C content and DNA-DNA hybridization. The results
      provided evidence in support of P. membranaefaciens encompassing distinct
      species. Only eight strains were certified as P. membranaefaciens and six were
      included in the same cluster, indicating that numerical analysis of fatty acid
      profiles points to genetic differences which remain undetectable by conventional
      phenotypic tests.

PMID- 8987446
TI  - Replicate plating: does it increase reliability?
AB  - As a part of a clinical study to evaluate the antibacterial effect of a topically
      applied erythromycin gel, microbiological specimens were taken from two groups of
      patients: one group using 2% erythromycin gel and the other group using a placebo
      gel. These specimens were plated in triplicate using a common source on
      bacteriological media using standard procedures. After the appropriate incubation
      times, the numbers of aerobic and anaerobic organisms were counted separately
      from each of three plates. A comparison of the bacterial colony counts from the
      replicate plates showed a high degree of similarity for each type of organism.
      Tests for treatment differences in organism counts were performed based on
      single, double and triplicate plating. The results obtained were almost
      identical, suggesting that replicate plating from a common source is no more
      accurate than single plating. The only apparent advantage of this type of
      replicate plating is heightened confidence in the reliability of bacterial counts
      from single plates.

PMID- 8987448
TI  - Detection of bacterial antigens using immuno-PCR.
AB  - A new and very sensitive antigen detection technique, immuno-polymerase chain
      reaction (immuno-PCR), was developed. This method is basically similar to the
      enzyme-linked immunosorbent assay which detects an antigen-antibody reaction, but
      instead of an enzyme being conjugated to an antibody, a DNA fragment is used and
      this DNA can be amplified by PCR. We applied this method to the detection of the
      fish pathogen, Pasteurella piscicida, in naturally infected yellowtail. Using
      immuno-PCR, 3.4 cfu ml-1 of bacteria could be detected. In comparison, ELISA
      detected only 3.4 x 10(4) cfu ml-1. Immuno-PCR is a powerful method for detection
      of pathogens in host tissues.

PMID- 8987449
TI  - Variation in Salmonella core lipopolysaccharide as detected by the monoclonal
      antibody M105.
AB  - The lipopolysaccharide antigenicity of 22 Salmonella strains (representing nine
      serogroups) and four non-salmonellae Enterobacteriaceae to the Salmonella genus
      specific monoclonal antibody M105 was analysed. The monoclonal antibody M105
      reacted with all 22 Salmonella strains. Probing SDS-PAGE separated LPS molecules
      with MAb M105 revealed that the antibody reacted with the core region of all
      Salmonella serovars. However, no reaction was obtained to the long-chain LPS of
      serovars O (Salm. adelaide and Salm. ealing), C1 (Salm. infantis, Salm.
      livingstone and Salm. virchow) or Salm. arizonae. It is plausible that the
      presence of a second core antigenic type results in the lack of reaction between
      long-chain LPS and the Salmonella genus specific monoclonal antibody M105.

PMID- 8987450
TI  - Survival of Salmonella enteritidis Pt4 and Salm. typhimurium Swindon in aerosols.
AB  - Small particle aerosols of plate-grown Salmonella enteritidis and Salm.
      typhimurium were generated and maintained within a rotating drum at 75% relative
      humidity and 24 degrees C for 2 h. Plate-grown organisms were found to be more
      aerosol-stable than broth-grown organisms. Differences were observed between the
      two species; plate-grown Salm. typhimurium retained 100% viability after 2 h
      compared to approximately 70% for plate-grown Salm. enteritidis. A large
      proportion of cells of both serotypes remained viable in aerosols after 2 h,
      confirming the potential for airborne transmission for these organisms, e.g.
      within henhouses and during food processing.

PMID- 8987451
TI  - Multiple strains of Saccharomyces cerevisiae on a single grape vine.
AB  - On the basis of the levels of secondary product formation four different
      phenotypes were represented among the 28 strains of Saccharomyces cerevisiae
      isolated during the spontaneous fermentation of grape juice. The genetic analysis
      indicated that four different strains, representing each phenotypic class, were
      derived, one from the other, by mutation. The spontaneous fermentation of a
      Malvasia must was dominated by different strains of Saccharomyces cerevisiae at
      different stages of fermentation.

PMID- 8987452
TI  - Growth/survival of Salmonella enteritidis on fresh poultry and fish stored under
      vacuum or modified atmosphere.
AB  - The effect of vacuum and modified atmosphere packaging on the growth/survival of
      Salmonella enteritidis on fresh poultry and fish (Boops boops) is described.
      Salmonella enteritidis survived but did not grow significantly in all samples
      (poultry or fish) at 3 degrees C. At 10 degrees C the numbers of Salm.
      enteritidis increases rapidly in vacuum-packed samples and in samples flushed
      with 100% N2, 20% CO2/80% O2 of both types of proteinaceous food. Growth was also
      evident in fish and poultry flushed with 100% CO2; however the rate of growth was
      greater in fish samples rather than in poultry.

PMID- 8987453
TI  - Leuconostoc mesenteroides subsp. mesenteroides FR52 synthesizes two distinct
      bacteriocins.
AB  - Mesenterocin 52, a bacteriocin produced by Leuconostoc mesenteroides subsp.
      mesenteroides FR52, was purified from producing cells by the adsorption
      desorption method, combined with reverse-phase high-performance liquid
      chromatography. The elution profile revealed the presence of two inhibitory peaks
      of activity, each displaying different inhibitory spectra. Mesenterocin 52A
      possessed a broad inhibitory spectrum, including anti-Listeria activity, while
      Mesenterocin 52B was only active against Leuconostoc spp. The amino acid sequence
      and M(r) of Mesenterocin 52A appeared identical to the previously described
      Mesentericin Y105. In contrast, Mesenterocin 52B possessed a M(r) of 3446 Da,
      corresponding to 32 amino acids and a sequence that shared no homology with known
      bacteriocins: NH2-KGVLGWLSMASSALTGPQQPNSPWLAKIKNHK.

PMID- 8987454
TI  - Lactate and acetate production in Listeria innocua.
AB  - Listeria innocua NCTC 11289 was grown aerobically in continuous culture in
      defined media at 30 degrees C. Both acetate and lactate were produced, the
      proportion of acetate decreased with increasing dilution rate. Enzymatic analysis
      showed lactate dehydrogenase was activated 10-fold by fructose-1, 6-bisphosphate.
      The presence of phosphate acetyltransferase and acetate kinase but not pyruvate
      oxidase was detected, suggesting the sequential action of phosphate
      acetyltransferase and acetate kinase to produce acetate from acetyl CoA via
      acetylphosphate.

PMID- 8987455
TI  - Methane production associated with rumen-ciliated protozoa and its effect on
      protozoan activity.
AB  - Methane production by methanogenic bacteria associated with ciliated protozoa in
      the rumen, and its effect on the metabolic activity of the protozoa, were
      measured in vitro. Apparent daily methane emission per protozoan cell ranged from
      a trace amount to 2 nmol. Enhanced substrate disappearance accompanIed
      methanogenesis.

PMID- 8987456
TI  - Bioinformatics--principles and potential of a new multidisciplinary tool.
AB  - The materials of bioinformatics are biological data, and its methods are derived
      from a wide variety of computational techniques. Recent years have seen an
      explosive growth in biological data, and the development of novel computational
      methods. These methods have become essential to research progress in structural
      biology, genomics, structure-based drug design and molecular evolution. The
      development and maintenance of a robust infrastructure of biological data is of
      equal importance if biotechnology is to take maximum advantage of research
      advances in a wide variety of fields. While bioinformatics has already made
      important contributions, it faces significant challenges as it matures.

PMID- 8987457
TI  - Database links are a foundation for interoperability.
AB  - Several techniques are being introduced into the bioinformatics community to
      permit interoperation between molecular biology databases (DBs). The common
      factor to these approaches is the creation of links between entities in different
      DBs. Links can connect pieces of information about a single protein that are
      partitioned across multiple DBs, and can also encode relationships between
      different biological entities, such as relationships between an enzyme, its gene
      and its catalytic activity. This article provides an overview of the DB
      interoperation problem, and offers several solutions. It discusses how links are
      used in molecular biology DBs, and describes the potential stumbling blocks when
      DB links are created and used.

PMID- 8987458
TI  - Computational comparisons of model genomes.
AB  - Complete genomes from model organisms provide new challenges for computational
      molecular biology. Novel questions emerge from the genome data obtained from the
      functional prediction of thousands of gene products. In this review, we present
      some approaches to the computational comparison of genomes, based on sequence and
      text analysis, and comparisons of genome composition and gene order.

PMID- 8987459
TI  - Informatics for ubiquitous sequencing.
AB  - Methods and technologies currently being developed promise an increase of between
      one and two orders of magnitude in the practical throughputs of DNA sequencing
      for gene discovery, expression analysis and variant analysis. Integrated
      laboratories will use all of these methods as components of a molecular strategy
      for the functional characterization of genes and their products. This review
      summarizes the types of data produced by these strategies, and the analysis and
      management challenges that they raise.

PMID- 8987461
TI  - Gene expression in normal and disease states--identification of therapeutic
      targets.
AB  - Analysis of gene-expression patterns derived from large expressed sequence tag
      (EST) databases has become a valuable tool in the discovery of therapeutic
      targets and diagnostic markers. Sequence data derived from a wide variety of cDNA
      libraries offer a wealth of information for identifying genes for pharmaceutical
      product development. Collecting, storing, organizing, analyzing and presenting
      cDNA expression data requires advanced bioinformatics methods and high
      performance computational equipment. Comparison of expression patterns from
      normal and disease tissues enables inferences about gene function to be made, and
      medically relevant genes as candidates for therapeutics research and development
      programs to be identified.

PMID- 8987460
TI  - Microbial pathogen genomes--new strategies for identifying therapeutics and
      vaccine targets.
AB  - Advances in high-throughput DNA-sequencing techniques have given us the
      unprecedented ability to rapidly determine the nucleotide sequences of entire
      bacterial genomes. The application of these methods to the genomes of microbial
      pathogens, combined with efficient analytical tools and genome-scale approaches
      for studying gene expression, is revolutionizing our approach to the selection of
      targets for drug screening and vaccine development. This is bringing new life to
      this important, but long-neglected, field of research.

PMID- 8987462
TI  - Gene patents--a time to balance access and incentives.
AB  - The issue of patents on inventions of genomic research is the subject of intense
      debate. The exchange of scientific information and access to new technologies are
      critical to biomedical research. Similarly, strong patent laws are necessary to
      encourage innovation. Thus, it is time to balance access and incentive. Patents
      claiming genes with purely speculative utilities should not be issued, and they
      possibly limit research. Reasonable access to properly patented genes should be
      provided for research, and exclusive positions maintained for commercial
      utilities. This will promote ready access to genomic information and fundamental
      technologies, while optimizing the discovery and disclosure of basic advances in
      biomedical research.

PMID- 8987463
TI  - Intellectual property issues in genomics.
AB  - Controversy over intellectual property rights in the results of large-scale cDNA
      sequencing raises intriguing questions about the roles of the public and private
      sectors in genomics research, and about who stands to benefit (and who stands to
      lose) from the private appropriation of genomic information. While the US Patent
      and Trademark Office has rejected patent applications on cDNA fragments of
      unknown function from the National Institutes of Health, private firms have
      pursued three distinct strategies for exploiting unpatented cDNA sequence
      information: exclusive licensing, non-exclusive licensing and dedication to the
      public domain.

PMID- 8987464
TI  - Bioinformatics in the pharmaceutical industry.
AB  - The great advances in human healthcare that are presaged by the Human Genome
      Project can be realized by the pharmaceutical industry. A prerequisite for this
      will be the successful integration of bioinformatics into most aspects of drug
      discovery. Although, from a scientific viewpoint, this is not a difficult
      problem, there are formidable technological obstacles. Once these are overcome,
      rapid progress can be expected.

PMID- 8987465
TI  - Company strategies for using bioinformatics.
AB  - Bioinformatics enables biotechnology companies to access and analyse their
      growing databases of experimental results, and to exploit public data from genome
      programmes and other sources. Traditionally occupying the domain of a 'guru'
      supplying answers to infrequent research questions, corporate bioinformatics is
      breaking down under the flood of data. New, more robust, professional and
      expandable systems will give scientists effective access to new tools. This
      review outlines how companies have evolved beyond the 'guru', and have organized
      their bioinformatics by acquiring or developing bioinformatics resources. It also
      describes why the biologist must be central to this process, and why this is a
      problem for computer professionals to solve, not for 'gurus'.

PMID- 8987466
TI  - Safe biotechnology. 7. Classification of microorganisms on the basis of hazard.
      Working Party "Safety in Biotechnology" of the European Federation Biotechnology.
AB  - The current systems for classifying human pathogens on the basis of hazard are
      well developed and their basic criteria are in general agreement one with
      another. Of more importance, the safety practices based on these classifications
      have generally been successful. They have enabled extensive research activities,
      medical practice and industrial production to be conducted on an ever-increasing
      scale, involving dangerous microorganisms (e.g. in vaccine production and
      treatment of infected patients) with a very low incidence of adverse effects on
      the workers involved and the general public. Although the EU has adopted a
      harmonised list of agents in groups 1-4 there is as yet no complete agreement
      among member states and individual microbiologists. The purpose of this paper is
      to present a historical survey and to discuss the current processes for
      identifying and classifying the hazards posed by the use of microorganisms in
      research and technology. This is essential in the design of appropriate methods
      of counteracting potential risks.

PMID- 8987467
TI  - The effect of pre- and pro-sequences and multicopy integration on heterologous
      expression of the Fusarium solani pisi cutinase gene in Aspergillus awamori.
AB  - A synthetic derivative of the cutinase cDNA of Fusarium solani pisi was expressed
      in Aspergillus awamori using the A. awamori endoxylanase II (exlA) promoter and
      terminator. The influence of the origin of the pre-sequence and the presence of a
      pro-sequence on the efficiency of extracellular cutinase production was analysed
      in single-copy transformants containing an expression cassette integrated at the
      pyrG locus. Transformants containing a construct encoding a direct, inframe
      fusion of the xylanase pre-peptide to the mature cutinase showed a 2-fold higher
      cutinase production level compared to strains containing constructs with an
      additional cutinase pro-peptide. The effect of multicopy integration of the
      expression cassette on cutinase production was analysed in strains with different
      numbers of a cutinase construct containing its own pre-pro-sequence. The
      multicopy strains showed a 6-to 12-fold increased production of extracellular
      cutinase relative to the single-copy strains. No linear dose response relation to
      the number of expression cassettes present in the strains was observed. The
      amount of active enzyme produced by the strains correlated with the amount of
      cutinase-specific mRNA, suggesting that cutinase overproduction is not limited at
      the level of translation or secretion.

PMID- 8987469
TI  - Isolation and characterization of a bacterial growth-stimulating peptide from a
      peptic bovine hemoglobin hydrolysate.
AB  - A peptide with a bacterial-growth-stimulating activity was isolated from a bovine
      hemoglobin hydrolysate by reversed-phase high-performance liquid chromatography.
      Its primary structure and molecular mass, determined by amino acid analysis and
      fast-atom bombardment mass spectrometry, were identical to those of fragment 48
      52 (Ser-Thr-Ala-Asp-Ala) of the beta chain of bovine hemoglobin. The
      microbiological tests in solid media demonstrated that this peptide exhibited a
      growth-stimulating activity on gram-negative bacteria.

PMID- 8987468
TI  - Application of factorial and Doehlert designs for optimization of pectate lyase
      production by a recombinant Escherichia coli.
AB  - The expression of a recombinant pectate lyase from Bacteroides thetaiotaomicron
      strain 217 was studied in Escherichia coli strain HB101(pBT4). First, two sets of
      complete 2(4) factorial designs were used to evaluate the influences of casamino
      acids, glucose, magnesium, calcium, tetracycline, ampicillin, tryptophan and MOPS
      buffer on pectate lyase production in a basal medium. While casamino acids,
      glucose and magnesium were found to be the prevalent factors, the presence of
      tetracycline, ampicillin and MOPS buffer were necessary for the reproducibility
      of the process, probably by increasing the plasmid stability. Secondly,
      application of the Doehlert design, a response-surface methodology, allowed a
      good prediction of pectate lyase production according to the variation in glucose
      and magnesium concentrations. This optimization strategy allowed the production
      of biomass and recombinant pectate lyase respectively to be increased from 0.2 gl
      1 to 1.9 gl-1 (dry weight) and from 10 units ml-1 to 210 units ml-1 within 24 h
      at 30 degrees C in shake flasks.

PMID- 8987470
TI  - Aerobic biodegradation of selected monoterpenes.
AB  - Batch experiments were conducted to assess the biotransformation potential of
      four hydrocarbon monoterpenes (d-limonene, alpha-pinene, gamma-terpinene, and
      terpinolene) and four alcohols (arbanol, linalool, plinol, and alpha-terpineol)
      under aerobic conditions at 23 degrees C. Both forest-soil extract and enriched
      cultures were used as inocula for the biodegradation experiments conducted first
      without, then with prior microbial acclimation to the monoterpenes tested. All
      four hydrocarbons and two alcohols were readily degraded. The increase in biomass
      and headspace CO2 concentrations paralleled the depletion of monoterpenes, thus
      confirming that terpene disappearance was the result of biodegradation
      accompanied by microbial growth and mineralization. Plinol resisted degradation
      in assays using inocula from diverse sources, while arbanol degraded very slowly.
      A significant fraction of d-limonene-derived carbon was accounted for as non
      extractable, dissolved organic carbon, whereas terpineol exhibited a much higher
      degree of utilization. The rate and extent of monoterpene biodegradation were not
      significantly affected by the presence of dissolved natural organic matter.

PMID- 8987471
TI  - Problems of translating heterologous genes in expression systems: the role of
      tRNA.
AB  - tRNA can have large effects on the expression and overexpression of heterologous
      genes in microbial expression systems through reduced translation and errors in
      amino acid sequences of protein products. Examples are given of large effects on
      gene expression related to tRNA content and to tRNA base modifications, both of
      which differ in heterologous expression systems compared to the cells from which
      the genes originally came. tRNA should be of greater concern in the expression of
      heterologous genes.

PMID- 8987472
TI  - Validation of a metabolic network for Saccharomyces cerevisiae using mixed
      substrate studies.
AB  - Setting up a metabolic network model for respiratory growth of Saccharomyces
      cerevisiae requires the estimation of only two (energetic) stoichiometric
      parameters: (1) the operational PO ratio and (2) a growth-related maintenance
      factor k. It is shown, both theoretically and practically, how chemostat
      cultivations with different mixtures of two substrates allow unique values to be
      given to these unknowns of the proposed metabolic model. For the yeast and model
      considered, an effective PO ratio of 1.09 mol of ATP/mol of O (95% confidence
      interval 1.07-1.11) and a k factor of 0.415 mol of ATP/C-mol of biomass (0.385
      0.445) were obtained from biomass substrate yield data on glucose/ethanol
      mixtures. Symbolic manipulation software proved very valuable in this study as it
      supported the proof of theoretical identifiability and significantly reduced the
      necessary computations for parameter estimation. In the transition from 100%
      glucose to 100% ethanol in the feed, four metabolic regimes occur. Switching
      between these regimes is determined by cessation of an irreversible reaction and
      initiation of an alternative reaction. Metabolic network predictions of these
      metabolic switches compared well with activity measurements of key enzymes. As a
      second validation of the network, the biomass yield of S. cerevisiae on acetate
      was also compared to the network prediction. An excellent agreement was found for
      a network in which acetate transport was modeled with a proton symport, while
      passive diffusion of acetate gave significantly higher yield predictions.

PMID- 8987473
TI  - Kinetics and stability of GM-CSF production by recombinant yeast cells
      immobilized in a fibrous-bed bioreactor.
AB  - The continuous production of murine granulocyte-macrophage colony-stimulating
      factor (GM-CSF) by recombinant yeast cells immobilized in a fibrous-bed
      bioreactor was studied. A high cell density of approximately 68 g/L and a GM-CSF
      productivity of approximately 3.5 mg/L.h were attained in the fibrous-bed
      bioreactor-fed with a rich (nonselective, pH 6.7) medium at a dilution rate of
      0.16 h-1. The GM-CSF production was stable even though the fraction of plasmid
      carrying cells in the reactor effluent gradually dropped below 5% over a period
      of 2 weeks. At the end of that period, the immobilized cells in the fibrous
      matrix still had a high fraction, approximately 26%, of plasmid-carrying cells.
      Similar results were obtained with reactors operated at 0.05 h-1 dilution rate
      and pH 4.0. Although the GM-CSF production was lower at pH 4, the reactor was
      stably operated for over 4 weeks without contamination or significant loss of
      productivity. The stable long-term GM-CSF production from the fibrous-bed
      bioreactor was attributed to the effect of cell immobilization on plasmid
      stability. Because GM-CSF production was growth-associated, as was found in batch
      fermentation with free cells, this stabilization effect cannot be attributed
      solely to the reduced cell growth in the immobilized cell environment. Plasmid
      carrying cells were preferentially retained in the fibrous matrix, perhaps
      because their abilities to adhere to the fiber surface and to form cell
      aggregates were higher than those of plasmid-free cells.

PMID- 8987475
TI  - Luciferase-dependent, cytochrome P-450-catalyzed dehalogenation in genetically
      engineered Pseudomonas.
AB  - To investigate the possibility of luciferase-dependent photoreduction of
      cytochrome P-450's in vivo, Vibrio harveyi luciferase was coexpressed with the
      bacterial cytochrome P-450cam in Pseudomonas putida. Luciferase expression was
      under the control of the Pm promoter from the meta-cleavage TOL operon,
      incorporated into the chromosome by a mini Tn5-mediated transposition. Cytochrome
      P-450cam expression was controlled by the Ptac-lac promoter on the broad host
      range vector pMMB206. Both proteins were expressed in Pseudomonas putida strain
      MTCC 102 (PpW). This strain does not harbor the cam plasmid, which encodes the
      enzymes responsible for degradation of the terpene camphor. The metabolic
      activity of the resulting strain (PpW-lux-cam) toward model halogenated compounds
      was studied. In the absence of the natural cytochrome P-450cam, electron transfer
      partners putidaredoxin (PR) and putidaredoxin reductase (Fp), and at low oxygen
      tension, the bacterial cells efficiently dehalogenate model chlorinated
      hydrocarbons in a light-independent reaction. Hexachloroethane and
      pentachloroethane were metabolized to tetrachloroethylene and trichloroethylene,
      respectively, at rates comparable to that of strain PpG786, which carries the
      scam plasmid. Reductive dehalogenation required the expression of both luciferase
      and cytochrome P-450 in the same cells. These results indicate that alternative
      electron transfer partners may be exploited for cytochrome P-450-dependent
      bioremediation strategies.

PMID- 8987474
TI  - Metabolic inhibitors, elicitors, and precursors as tools for probing yield
      limitation in taxane production by Taxus chinensis cell cultures.
AB  - Inhibition of biosynthetic enzymes and translation and translocation processes,
      elicitation, and precursor feeding were used to probe biosynthetic pathway
      compartmentation, substrate-product relationships, and yield limitation of the
      diterpenoid taxanes in cell cultures of Taxus chinensis (PRO1-95). The results
      suggest the following: (i) the source of isopentenyl pyrophosphate in taxane
      production is likely plastidic rather than cytoplasmic; (ii) baccatin III may not
      be a direct precusor of Taxol (Taxol is a registered trademark of Bristol-Myers
      Squibb for paclitaxel); (iii) baccatin III appears to have cytoplasmic and
      plastidic biosynthetic components, while Taxol production is essentially
      plastidic; and (iv) arachidonic acid specifically stimulates Taxol production but
      does not have a significant effect on baccatin III yield. Semiempirical
      mathematical models were used to describe these results and predict potential
      yield-limiting steps. Model simulations suggest that, under current operating
      conditions, Taxol production in Taxus chinensis (PRO1-95) cultures is limited by
      the ability of the cells to convert phenylalanine to phenylisoserine rather than
      by the branch-point acyl transferase. This result is supported by the lack of
      improvement of Taxol yield by feeding phenylalanine or benzoylglycine. The
      methods described in this article, while specifically expanding our knowledge of
      taxane production in PRO1-95 cultures, could be generally useful in investigating
      complex aspects of secondary metabolic pathways in plant cell cultures,
      especially when details of the pathway and compartmentation are sparse.

PMID- 8987476
TI  - Mass transfer of antibiotics adsorbed by human serum albumin in hemodialyzers.
AB  - The removal rate of a drug by a hemodialyzer is very important to determine the
      dosage of the drug to a patient without kidney function. Mass transfer of a drug
      in a hemodialyzer and a patient's body is more complicated than that of ordinary
      solutes because most drugs are adsorbed by serum albumin. In this paper, we
      reveal the adsorption characteristics of five clinical antibiotics onto human
      serum albumin (HSA) with new experimental methods and discuss the influence of
      adsorption characteristics on removal of antibiotics by hemodialyzers using
      mathematical models. The adsorption equilibrium of the antibiotics with HSA
      followed the Langmuir isotherm. Adsorption rates of the antibiotics onto HSA were
      measured using a constant-flow stirred tank reactor with an ultrafiltration
      module. A kinetic model for antibiotic transfer in a hemodialyzer and a patient's
      body was derived with the parameters obtained by the above experiments. Validity
      of the model was confirmed by dialysis experiments using hemodialyzers and
      antibiotic solutions including HSA. Removal estimation of a drug by hemodialysis
      therapy is feasible by the model with the parameters of the Langmuir isotherm for
      the drug.

PMID- 8987477
TI  - Heat flux measurements for the fast monitoring of dynamic responses to glucose
      additions by yeasts that were subjected to different feeding regimes in
      continuous culture.
AB  - Heat measurements have been successfully as an analytical tool for the study of
      the dynamics of energy metabolism of Saccharomyces cerevisiae and Candida utilis
      grown in continuous culture under fluctuating substrate supply. A low average
      dilution rate (D = 0.05 h-1) was maintained either by adding the medium as
      continuously (dropwise) as possible or (blockwise) by adding the medium at high
      speed during a short period (D = 0.5 h-1 for 40 s) and not at all during the
      following period (D = 0.00 h-1 for 360 s). The resulting biological activity was
      monitored on-line with conventional (O2 and CO2) off-gas analyses, DOT
      measurements, and heat flux measurements. In C. utilis cultures, the biomass
      specific maximum oxygen consumption rate (qO2,max), the biomass yield (Ys,x), and
      the dynamic responses to a glucose pulse and to a change in feeding regime were
      not significantly affected by different preceding feeding regimes. In contrast,
      S. cerevisiae grown in continuous culture with blockwise feed showed a 50%
      increase in qO2,max and a 25% drop in Ys,x compared to the culture grown with
      dropwise feed. The dynamic response to a glucose pulse (0.6 g L-1) was slower for
      the continuous (dropwise) than for the blockwise grown S. cerevisiae. With a
      second testing method for the dynamic response of the yeasts, the feeding regime
      was changed. The blockwise fed S. cerevisiae proved to be better "trained" to
      cope with sudden changes in glucose supply and, therefore, was more "shockproof"
      toward a change in feeding regime. This clearly points to major differences in
      the intracellular metabolic flux control between the yeasts. These findings are
      of relevance for industrial baker's yeast production, where reactor mixing times
      of one to several minutes are not uncommon. The observed, heat production,
      together with the dissolved oxygen concentration, appeared to give the fastest
      response to actual changes in the culture. It is suggested that heat measurements
      can be a very useful tool to monitor and control the growth of S. cerevisiae in
      laboratory and industrial fermenter operations.

PMID- 8987478
TI  - Competitive immunosorbent assays using ligand-enzyme conjugates bifunctional
      liposomes: theory and experiment.
AB  - Two models of immunoadsorbent assays are developed that describe the competitive
      adsorption of labeled antigen and unlabeled analyte to antibody binding sites
      immobilized on a solid surface. In the first model, a small labeled antigen and a
      small unlabeled analyte compete with only binding site limitations and no steric
      limitations. A multicomponent langmuir isotherm results that is sufficient to
      quantify competitive adsorption. This model can describe, with no adjustable
      parameters, the data of competitive assays for biotin using biotinylated
      horseradish peroxidase (B-HRP) over a wide range of anti-biotin antibody (ABA)
      surface densities. In the second model, the small unlabeled analyte competes with
      a large colloidal particle containing many antigens and enzyme labels attached to
      its surface. This model quantifies the steric interference that large particles
      can experience upon binding (large ligand effect) due to the lower probability of
      finding an available area of the right size to accommodate the larger adsorbent.
      This large ligand model also takes into account the increased probability of
      binding a large particle due to the larger number of antibody binding sites
      covered per collision. The resulting model is used to analyze the competitive
      assay data of biotin competing with liposomes to which many biotin and HRP
      molecules have been conjugated. This analysis is of interest because previous
      work has shown that these bifunctional liposomes can reduce the detection limit
      for antigens in bulk solution relative to assays performed with conventional
      small labeled antigens.

PMID- 8987479
TI  - Biological verification of fluid-to-particle interfacial heat transfer
      coefficients in a pilot scale holding tube simulator.
AB  - Inactivation kinetics of immobilized bovine pancrease trypsin (type III) was used
      in conjunction with a finite difference model to verify fluid-to-particle heart
      transfer coefficients to particulates in a holding tube of a pilot scale aseptic
      processing simulator operated at temperature ranging from 90 and 110 degrees C.
      The enzyme was sealed in a stainless steel capsule, which was pretested to be
      suitable for high-temperature, shortime application, and embedded at the center
      of a finite cylindrical particle. The percentage retention of the enzyme activity
      was calculated by using transient temperatures and their respective D values in a
      finite difference program. Heat transfer coefficients estimated for the potato
      particles under similar experimental conditions were used as input data.
      Excellent comparison was observed between predicted and measured percentage
      retention of enzyme activity.

PMID- 8987480
TI  - Bioreactor strategies for the treatment of growth-inhibitory waste: an analysis
      of thiodiglycol degradation, the main hydrolysis product of sulfur mustard.
AB  - The microbial degradation of thiodiglycol, the primary hydrolysis product of
      sulfur mustard, by a pure culture of Alcaligenes xylosoxydans ssp. xylosoxydans
      (SH91) was accomplished in laboratory scale stirred tank reactors. This is a
      major component of the overall biodegradation process proposed for the complete
      mineralization of sulfur mustard. Several configurations were evaluated for
      degradation efficiency including batch, repeated batch, continuous stirred tank
      reactor (CSTR), and two-stage series CSTR. The repeated batch reactor provided
      the highest degradation rate of thiodiglycol. Further, this method degraded
      thiodiglycol in the liquid broth to below the detection limits (0.03 mM). Both
      batch and repeated batch experiments were simulated by an unstructured
      mathematical model. Simulation results were in agreement with the experimental
      data, particularly at low TDG concentration (around 30 mM). This study
      demonstrates the degradation of thiodiglycol using bioreactors and, more
      generally, is an experimental study of bioreactor designs for the degradation of
      growth-inhibitory substances.

PMID- 8987481
TI  - Ty1-mediated integration of expression cassettes: host strain effects, stability,
      and product synthesis.
AB  - The yeast retrotransposon Ty1 has been used to insert multiple copies of
      heterologous genes into the genome of Saccharomyces cerevisiae. Amplification
      using a GAL1-regulated Ty1 element carrying a 4.6 kilobase pair expression
      cassette (Escherichia coli lacZ structural gene under the control of the yeast
      CUP1 promoter, and the bacterial neo gene) was compared with that of a GAL1
      regulated Ty1 element carrying only the neo gene. Mobilization of Ty1 was induced
      from a chromosomal element and a 2 mu-plasmid-based element; similar results were
      obtained for both locations. The two marked Ty1 cassettes were successfully
      integrated into the genomes of three different S. cerevisiae strains.
      Efficiencies were found to vary significantly between strains. The size of the
      inserted cassette was also important; the efficiency for the CUP1p-lacZ-neo
      cassette was much lower than that for the neo cassette in the same host. All
      amplified copies were found to be quite stable with or without expression for at
      least 50 generation in nonselective medium; moreover, there were no significant
      effects on the growth of the cells. After integration, beta-galactosidase
      specific activity from the lacZ construct in the three hosts was found to
      correlate well with the copy number of the CUP1p-lacZ expression cassette
      amplified by the Ty1 retrotransposon.

PMID- 8987482
TI  - Sialidase activity in culture fluid of Chinese hamster ovary cells during batch
      culture and its effects on recombinant human antithrombin III integrity.
AB  - Sialidase activity in cell-free supernatant of batch-cultivated Chinese hamster
      ovary (CHO) cells producing human recombinant antithrombin III (rhAT III) was
      monitored during cultivation using 4-methylumbelliferyl substrate and HPLC for
      free sialic acid determination. Supernatant sialidase as well as lactate
      dehydrogenase activity increased significantly during batch growth. The enhanced
      number of dead cells correlated with increasing sialidase activity which seemed
      to be principally due to cell lysis, resulting in release of cytosolic sialidase.
      Loss of terminally alpha (2-->3) bound sialic acids of the oligosaccharides of
      rhAT III was analyzed in lectin-based Western blot and enzyme-linked lectin
      assays, using Maackia amurensis and Datura stramonium agglutinins for specific
      determination of Neu5Ac alpha (2-->3)Gal- and Gal beta (1-->4)-GlcNAc-terminated
      glycoproteins, respectively. Results show a remarkable loss of terminal sialic
      acids of rhAT III along with decrease in CHO cell viability and concomitant
      increase of dead cells throughout long-term batch cultivation. To avoid this
      degradation effect, process parameters forcing high viability are essential and
      harvesting of culture at an early time even at suboptimal recombinant protein
      concentration is highly recommended to avoid product desialylation.

PMID- 8987483
TI  - A quantitative immunoassay utilizing Escherichia coli cells possessing surface
      expressed single chain Fv molecules.
AB  - A facile, quantitative immunoassay is described that utilizes Escherichia coli
      (E. coli) bacteria expressing single chain Fv (scFv) antibody fragments attached
      to the cell surface. A Scatchard analysis demonstrated that the antibodies on the
      surface of the cells retained full binding activity (Kd = 2.2 x 10(-9) M) and
      that there are 60,000 scFv molecules per cell. The cells are used as the antibody
      reagent in the assay, and, following incubation with analyte, simple
      centrifugation is used to separate the antibody-bound from unbound analyte. The
      immunoassay is rapid and accurate down to the nanomolar level. In addition, a
      variety of detection strategies can be used, and the immunoassay is not adversely
      affected by the presence of animal serum. A key advantage of the new immunoassay
      is that the antibody reagent can be inexpensively produced in a "ready to use"
      form by simply growing cultures of the bacteria.

PMID- 8987484
TI  - Asymmetric bioreduction of a ketosulfone to the corresponding trans
      hydroxysulfone by the yeast Rhodotorula rubra MY 2169.
AB  - A microbial screen identified the yeast Rhodotorula rubra MY 2169 as a suitable
      biocatalyst for the asymmetric bioreduction of a ketosulfone (5,6 dihydro-6(s)
      propyl-4H-thieno[2,3b] thiopyran-4-one-7,7-dioxide) to the corresponding trans
      hydroxysulfone. This synthesizer is a precursor to the carbonic anhydrase
      inhibitor L-685,393, a new drug candidate targeted for the treatment of ocular
      glaucoma. Process development studies revealed that the rate of bioreduction was
      sensitive to temperature, pH, solvent concentration and the physiological state
      of the yeast cells. The maximum specific bioreduction rate was achieved by
      employing cells harvested in the stationary phase of growth. The diastereomeric
      excess of the trans-hydroxysulfone produced was found to be only affected by the
      residual amount of ketosulfone present in the bioconversion medium; therefore,
      when close monitoring of the residual ketosulfone was implemented, the desired
      enantiomeric excess was achieved at harvest. When scaled up, this bioreduction
      process supported the production of gram quantities of highly optically pure
      trans-hydroxysulfone (diastereomeric excess > 96%).

PMID- 8987486
TI  - Control of pellet morphology of filamentous fungi in fluidized bed bioreactors by
      means of a pulsing flow. Application to Aspergillus niger and Phanerochaete
      chrysosporium.
AB  - The application of a pulsing flow to fluidized-bed bioreactors in order to
      control pellet morphology of filamentous fungi was investigated. The operation at
      an optimum pulsation frequency allowed two effects: a narrower pellet size
      distribution which improves fluidization quality, and an enhanced production of
      citric acid by Aspergillus niger and manganese peroxidase by Phanerochaete
      chrysosporium. In the case of A. niger, the pellet diameter corresponding to the
      pulsed system operated at 0.35 s-1 was kept between 3.3 +/- 0.1 mm after 22 days
      of operation; however, in the nonpulsed bioreactor which was operative for only
      11 days, pellets with a diameter of 6.7 +/- 0.3 mm were produced. Similar results
      were obtained in the case of P. chrysosporium, since with a pulsing frequency of
      0.0625 s-1, a pellet diameter of 2.1 +/- 0.4 mm after 34 days of operation was
      maintained. On the contrary, the system without pulsation presented great
      conglomerates of mycelia with an average diameter of 3 cm surrounded by free
      pellets with a diameter distribution of 2.75 +/- 0.5 mm. The nonpulsed bioreactor
      was only operative for 14 days. Both citric acid and manganese peroxidase
      production attained higher values and were maintained longer in the pulsed
      bioreactor.

PMID- 8987485
TI  - Kinetics of taxol production and nutrient use in suspension cultures of Taxus
      cuspidata in shake flasks and a Wilson-type bioreactor.
AB  - Suspension cultures of Taxus cuspidata were grown in shake flasks and Wilson-type
      reactors where bubbled air provided both agitation and mixing. Taxol titers of 22
      mg l-1 were achieved for both configurations in 20 days for a volumetric
      productivity of 1.1 mg l-1 day-1. This productivity is many-fold higher than
      reported for other Taxus sp. suspension cultures. Taxol was released to the
      extracellular medium as it was produced with little intracellular retention (< or
      = 10%). Taxol production occurred during the last seven days of the cultivation
      period and was not growth-associated. Although the same taxol titers could be
      obtained in both reactor types, nutrient uptake rates were faster in the Wilson
      type reactor than in shake flasks. Formation of a growth ring in the Wilson-type
      reactor reduced measured cell mass yields.

PMID- 8987487
TI  - Site-directed mutations of the catalytic and conserved amino acids of the
      neuraminidase gene, nanH, of Clostridium perfringens ATCC 10543.
AB  - The small nanH gene encoding the neuraminidase from Clostridium perfringens ATCC
      10543 was cloned in JM109 using pUC19 as a vector. Sequence analysis revealed an
      ORF encoding 382 amino acids without a signal peptide sequence. Four regions of
      amino-acid sequence, 71-82, 140-151, 208-219, and 255-266 constituted four
      repeated and conserved sequence motifs-Ser-X-Asp-X-Gly-X-Thr-Trp-, the "Asp
      boxes." When compared, the nanH polypeptides of C. perfringens ATCC 10543 and
      Salmonella typhimurium LT12 shared 33% sequence identity and 60% similarity if
      conservative replacements were included. The homology-modeled structure of C.
      perfringens NanH showed the same folding topology as the x-ray three-dimensional
      structure of NanH in S. typhimurium LT12. Amino acid residues Arg37, Arg56,
      Asp62, His63, Asp100, Glu230, Asp247, Tyr347, and Glu362 located around the
      pocket of modeled C. perfringens small nanH were superimposed with the active
      site pocket of S. typhimurium LT12, nanH. The catalytic amino-acid residues as
      well as the role of the "Asp boxes" have not been characterized for C.
      perfringens and S. typhimurium. In this study, Asp100, Glu230, and Asp62 were
      found to be involved in the catalytic activity of C. perfringens small nanH with
      immunoreactive properties and site-directed mutagenesis analysis. Four "Asp-box"
      motifs were found remote from the active-site pocket. Mutational and
      immunoreactive analysis of the highly conserved amino acids located in the "Asp
      boxes" suggest that these highly conserved residues are important in maintaining
      the tertiary structure of NanH. The results of this study provide some knowledge
      for the design of new inhibitors of small neuraminidase.

PMID- 8987488
TI  - Construction and use of recombinant Escherichia coli strains for the synthesis of
      toluene cis-glycol.
AB  - The toluene dioxygenase genes derived from Pseudomonas putida NCIMB 11767 were
      subcloned from a previously constructed recombinant plasmid, pIG, using pUC18 as
      the cloning vector and E. coli TG2 as the host strain. The resulting strain, E.
      coli TG2 (p1/1), produced toluene cis-glycol when grown in LB broth or minimal
      medium in the presence of toluene. Restriction mapping and partial DNA sequencing
      provided evidence for the presence of ORFs with extensive homology to parts of
      the tod operon from P. putida F1. The clones exhibited some residual toluene cis
      glycol dehydrogenase activity which resulted in the formation of small amounts of
      3-methylcatechol. Expression of the dioxygenase was induced by toluene, but was
      not directed by the lac promoter within the cloning vector. The clones were
      assessed for toluene cis-glycol production in pH-controlled batch cultures, and
      the maximum product concentration obtained was 1.02 g l-1. Product formation was
      dependent upon the presence of glucose in the culture medium. Although the
      substrate was toxic, the biotransformation was apparently limited by the supply
      of toluene. The results suggest that it should be possible to improve toluene cis
      glycol production by recombinants substantially by improving both the strain and
      fermentation process.

PMID- 8987489
TI  - Fungal melanins and their interactions with metals.
AB  - Fungal melanins are dark brown or black pigments located in cell walls. They also
      exist as extracellular polymers. Melanized fungi possess increased virulence and
      resistance to microbial attack as well as enhanced survival while under
      environmental stress. Melanins contain various functional groups which provide an
      array of multiple nonequivalent binding sites for metal ions. Pigmented
      Cladosporium cladosporoides was shown to biosorb 2.5- to four-fold more Ni, Cu,
      Zn, Cd, and Pb than albino Penicillium digitatum and at four- to six-fold higher
      rates. Metal desorption was significantly lower for extracellular melanin than
      from pigmented or albino biomass which indicated the strength of the melanin
      metal bond. At equilibrium, tributyltin chloride (TBTC) concentrations of 2.5 mM,
      pigmented and albino Aureobasidium pullulans absorbed approximately 0.9 and 0.7
      mumol TBTC mg -1 dry wt, respectively, whereas purified extracellular melanin
      exhibited uptake levels of approximately 22 mumol TBTC mg-1 dry wt at an
      equilibrium concentration of only 0.4 mM. Addition of melanin to the growth
      medium reduced the toxic effect of CuSO4 and TBTC due to melanin metal binding
      and sequestration.

PMID- 8987490
TI  - Tracing the interaction of bacteriophage with bacterial biofilms using
      fluorescent and chromogenic probes.
AB  - Phages T4 and E79 were fluorescently-labeled with rhodamine isothiocyanate
      (RITC), fluoroscein isothiocyanate (FITC), and by the addition of 4'6-diamidino-2
      phenylindole (DAPI) to phage-infected host cells of Escherichia coli and
      Pseudomonas aeruginosa. Comparisons of electron micrographs with scanning
      confocal laser microscope (SCLM) images indicated that single RITC-labeled phage
      particles could be visualized. Biofilms of each bacterium were infected by
      labeled phage. SCLM and epifluorescence microscopy were used to observe
      adsorption of phage to single-layer surface-attached bacteria and thicker
      biofilms. The spread of the recombinant T4 phage, YZA1 (containing an rII-LacZ
      fusion), within a lac E. coli biofilm could be detected in the presence of
      chromogenic and fluorogenic homologs of galactose. Infected cells exhibited blue
      pigmentation and fluorescence from the cleavage products produced by the phage
      encoded beta-galactosidase activity. Fluorescent antibodies were used to detect
      non-labeled progeny phage. Phage T4 infected both surface-attached and surface
      associated E. coli while phage E79 adsorbed to P. aeruginosa cells on the surface
      of the biofilm, but access to cells deep in biofilms was somewhat restricted.
      Temperature and nutrient concentration did not affect susceptibility to phage
      infection, but lower temperature and low nutrients extended the time-to-lysis and
      slowed the spread of infection within the biofilm.

PMID- 8987491
TI  - Electrotransformation of Clostridium thermosaccharolyticum.
AB  - Transformation of the thermophile Clostridium thermosaccharolyticum ATCC 31960
      was achieved using plasmid pCTC1 and electroporation. Evidence supporting
      transformation was provided by Southern blots, detection of the plasmid in 10 out
      of 10 erythromycin-resistant clones, retransformation of E. coli and C.
      thermosaccharolyticum with plasmid DNA isolated from C. thermosaccharolyticum,
      and a proportional relationship between the number of transformants and the
      amount of DNA added. Transformation efficiencies were very low for plasmid DNA
      prepared from E. coli (0.6 transformants mg-1 DNA), although somewhat higher for
      plasmid DNA prepared from C. thermosaccharolyticum (52 transformants mg-1 DNA).
      Transformation-dependent erythromycin resistance indicates that an adenosine
      methylase gene originating from Enterococcus faecalis, a mesophile, is expressed
      in C. thermosaccharolyticum. The plasmid pCTC1 appears to be replicated
      independently of the chromosome, as indicated by visualization of recovered
      plasmid on gels, and retransformation using recovered plasmid. pCTC1 is
      maintained in C. thermosaccharolyticum at both 45 and 60 degrees C. Restriction
      analysis showed little or no rearrangement occurred upon passage through the
      thermophile.

PMID- 8987492
TI  - Effect of inoculum level of xylitol production from rice straw hemicellulose
      hydrolysate by Candida guilliermondii.
AB  - The effect of inoculum level on xylitol production by Candida guilliermondii was
      evaluated in a rice straw hemicellulose hydrolysate. High initial cell density
      did not show a positive effect in this bioconversion since increasing the initial
      cell density from 0.67 g L-1 to 2.41 g L-1 decreased both the rate of xylose
      utilization and xylitol accumulation. The maximum xylitol yield (0.71 g g-1) and
      volumetric productivity (0.56 g L-1 h-1) were reached with an inoculum level of
      0.9 g L-1. These results show that under appropriate inoculum conditions rice
      straw hemicellulose hydrolysate can be converted into xylitol by the yeast C.
      guilliermondii with efficiency values as high as 77% of the theoretical maximum.

PMID- 8987493
TI  - The effect of novobiocin on solvent production by Clostridium acetobutylicum.
AB  - Cells of Clostridium acetobutylicum treated with novoblocin, a DNA gyrase
      inhibitor, produced higher butyrate levels and lower solvent levels with acetone
      being the most affected. Seven enzyme activities involved in acid and solvent
      production were analyzed. Among them, only CoA transferase, required for acetone
      formation and acid uptake, experienced a significant decrease in activity. As in
      Escherichia coli and Bacillus subtilis, DNA from C. acetobutylicum became less
      negatively supercoiled in the early stationary phase (solventogenic stage), as
      shown by analysis of linking number of a reporter plasmid by agarose gel
      electrophoresis in the presence of chloroquine.

PMID- 8987494
TI  - Genes, enzymes and secondary metabolites in industrial microorganisms. The 1995
      Thom Award Lecture.
AB  - Apparently contrasting approaches, ie genetic engineering and screening of new
      microorganisms, play essential complementary roles to develop current industrial
      microbiology. Three topics, production and modification of milk-clotting
      proteinases by genetic engineering, hormonal control of secondary metabolism in
      streptomycetes, and screening of bioactive metabolites, are introduced as cases
      of such a hybrid approach, while symbiotic microorganisms are discussed as an
      example of the vast terra incognita still remaining for the future microbiology.

PMID- 8987495
TI  - Biomass relationship to growth and phosphate uptake of Pseudomonas fluorescens,
      Escherichia coli and Acinetobacter radioresistens in mixed liquor medium.
AB  - The ability of Pseudomonas fluorescens, Escherichia coli and Acinetobacter
      radioresistens to remove phosphate during growth was related to the initial
      biomass as well as to growth stages and bacterial species. Phosphate was removed
      by these bacteria under favourable conditions as well as under unfavourable
      conditions of growth. Experiments showed a relationship between a high initial
      cell density and phosphate uptake. More phosphate was released than removed when
      low initial cell densities (10(2)-10(5) cells ml-1) were used. At a high initial
      biomass concentration (10(8) cells ml-1), phosphate was removed during the lag
      phase and during logarithmic growth by P. fluorescens. Escherichia coli, at high
      initial biomass concentrations (10(7) cells ml-1), accumulated most of the
      phosphate during the first hour of the lag phase and/or during logarithmic growth
      and in some cases removed a small quantity of phosphate during the stationary
      growth phase. Acinetobacter radioresistens, at high initial cell densities
      (10(6), 10(7) cells ml-1) removed most of phosphate during the first hour of the
      lag phase and some phosphate during the stationary growth phase. Pseudomonas
      fluorescens removed phosphate more than A. radioresistens and E. coli with
      specific average ranges from 3.00-28.50 mg L-1 compared to average ranges of 4.92
      17.14 mg L-1 for A. radioresistens and to average ranges of 0.50-8.50 mg L-1 for
      E. coli.

PMID- 8987496
TI  - Soy-based medium for ethanol production by Escherichia coli KO11.
AB  - An optimized soy-based medium was developed for ethanol production by Escherichia
      coli KO11. The medium consists of mineral salts, vitamins, crude enzymatic
      hydrolysate of soy and fermentable sugar. Ethanol produced after 24 h was used as
      an endpoint in bioassays to optimize hydrolysate preparation. Although longer
      fermentation times were required with soy medium than with LB medium, similar
      final ethanol concentrations were achieved (44-45 g ethanol L-1 from 100 g
      glucose L-1). The cost of materials for soy medium (excluding sugar) was
      estimated to be $0.003 L-1 broth, $0.06 L-1 ethanol.

PMID- 8987497
TI  - Flagellar proteins of motile spores of Actinomycetes.
AB  - Flagella of some of the actinoplanete genera were purified and the molecular
      sizes of their flagellin subunits compared by SDS-PAGE analysis to flagellins of
      cells of other bacteria. Several species of Actinoplanes have a major flagellar
      protein of subunit sizes of 42-43 kDa and a lesser amount of a second protein,
      possibly a minor flagellin subunit, of 60 kDa. The flagellar protein sizes of
      other actinoplanetes ranged from 32-43 kDa (major) and 48-58 kDa (minor).
      Antibodies formed against the 42-kDa protein of A. rectilineatus showed cross
      reactivity in Western blots against flagellar proteins of spores of other
      Actinoplanes species, two species of Dactylosporangium and an Ampullariella
      species. Cross-reactivity was also observed with motile cells of two other
      actinomycetes, Arthrobacter atrocyaneus and a Geodermatophilus species, and with
      Bacillus subtilis. No cross-reactivity was observed with Escherichia coli or
      Planomonospora parontospora flagellar proteins. The amino acid composition and
      partial N-terminal sequence of the 42-kDa flagellar protein of A. rectilineatus
      was compared to literature data for other bacterial flagellins and found to be
      most similar to B. subtilis 168.

PMID- 8987498
TI  - A complete computer monitoring and control system using commercially available,
      configurable software for laboratory and pilot plant Escherichia coli
      fermentations.
AB  - The advent of inexpensive computers and associated control and data acquisition
      software makes possible the development of sophisticated, configurable,
      integrated monitoring and control systems for small-scale laboratory and pilot
      scale fermentors at low cost. We describe here the implementation of such a
      system, the interfacing of off-line instruments to enhance real time data
      analysis, low level process control and several substrate feeding protocols.

PMID- 8987499
TI  - Stabile production of a thrombin resistant pro-urokinase derivative (PRO-UKS1) by
      Namalwa KJM-1 cells adapted to serum-free medium.
AB  - Pro-UKS1 was designed as a thrombin-resistant derivative of pro-urokinase (pro
      UK) by introducing a glycosylation site using site-directed mutagenesis. An
      expression plasmid for pro-UKS1, pMo1UKS1SEd1-5, was constructed and introduced
      into Namalwa KJM-1 cells (Hosoi et al., 1988), and cells resistant to G418 and
      Methotrexate (MTX) were obtained. Amongst them, the highest pro-UKS1 producer
      (resistant to 500 nM of MTX), clone 41-8, was selected and further characterized.
      Clone 41-8 was cultured in serum-free ITPSGF medium (Hosoi et al., 1988). Under
      the conventional conditions, the concentration of pro-UKS1 reached 26 micrograms
      ml-1. Addition of glucose and tri-iodothyronine (T3) improved productivity, and
      the maximal productivity of pro-UKS1 was 67 micrograms ml-1 day-1. In this
      conditioned medium, content of pro-UKS1 was above 80% of total proteins.

PMID- 8987500
TI  - Succinoyl trehalose lipid induced differentiation of human monocytoid leukemic
      cell line U937 into monocyte-macrophages.
AB  - A novel type of succinoyl trehalose lipid (STL-1) prepared from n-hexadecane
      culture of Rhodococcus erythropolis SD-74 markedly inhibited the growth of a
      human monocytoid leukemic cell line, U937, and induced its morphological
      alteration along a monocyte-macrophage lineage. STL-1 markedly increased
      differention-associated characteristics in macrophage, such as nitroblue
      tetrazolium reducing ability, appearance of Fc receptor, phagocytic activities in
      U937. Furthermore, U937 cells, which were activated with STL-1 exhibited
      cytotoxic activity against human lung carcinoma cell line A549. However, STL-1
      did not affect growth of a normal human fetal lung cell line TIG-1. The
      individual components of STL-1, neither sugar moiety nor fatty acids in the free
      form, were effective at inducing the differentiation of U937 cell. From these
      results, we concluded that STL-1 has low cytotoxicity against normal human cells
      and the ester molecule itself is responsible for the activity of inducing
      differentiation of human monocytoid leukemic cell line U937 into monocyte
      macrophage which results in the stimulation of the production of some cytotoxic
      substances.

PMID- 8987501
TI  - Modulation of oligosaccharide structure of a pro-urokinase derivative (pro-UK
      delta GS1) by changing culture conditions of a lymphoblastoid cell line Namalwa
      KJM-1 adapted to serum-free medium.
AB  - Pro-UK delta GS1 was designed as a long-life and thrombin-resistant derivative of
      pro-urokinase (pro-UK) by deleting the growth factor domain of pro-UK and
      introducing a glycosylation site near the thrombin cleaving site for thrombin
      resistance using site-directed mutagenesis. An expression plasmid for pro-UKDGS1,
      pIH1UK delta GS1SEd1-5 was constructed and introduced into Namalwa KJM-1, a
      lymphoblastoid cell line adapted to serum-free medium, and cells resistant to
      G418 and Methotrexate (MTX) were obtained. Amongst them, the highest pro-UK delta
      GS1 producer (resistant to 200 nM of MTX), clone 2-9, was selected and used for
      further studies. Under the conventional conditions, i.e. at 37 degrees C in serum
      free ITPSGF medium (based on RPMI-1640 medium), the oligosaccharide structure of
      pro-UK delta GS1 produced by clone 2-9 mainly consisted of fucose (Fuc)
      containing biantennary complex-type oligosaccharide. Addition of dexamethasone
      (Dex), changed the carbohydrate contents in the media, and a shift down of
      incubation temperature caused a change in oligosaccharide structure of pro-UK
      delta GS1 from mainly Fuc-containing biantennary to mainly Fuc-containing tri-
      and tetraantennary complex-type oligosaccharide. The modulated pro-UK delta GS1
      showed superior in vivo activity for a canine femoral thrombosis formed by
      inserting a copper-coil.

PMID- 8987503
TI  - Identification of three C20-gibberellins: GA97 (2 beta-hydroxy-GA53), GA98 (2
      beta-hydroxy-GA44) and GA99 (2 beta-hydroxy-GA19).
AB  - Three new C20-gibberellins, GA97 (2 beta-hydroxy-GA53), GA98 (2 beta-hydroxy
      GA44) and GA99 (2 beta-hydroxy-GA19), have all been isolated from spinach, GA97
      also from tomato root cultures and pea pods, and GA98 from maize pollen. The
      structures of these compounds were established by GC-mass spectrometric
      comparisons of the trimethylsilylated methyl esters with authentic samples
      prepared from gibberellic acid (GA3).

PMID- 8987502
TI  - Establishment of a novel embryonic stem cell line by a modified procedure.
AB  - To generate mutant mice, embryonic stem (ES) cells are used as a vehicle for
      introducing mutations. The establishment of ES cells is difficult because it
      requires specific skills and it is time-consuming. We established a novel ES cell
      line derived from hybrid mice between C57BL/6 and DBA/2 using a modified method.
      To collect a large number of preimplantational embryos, we collected embryos at
      the 8-cell stage and cultured them to blastocysts, whereas the usual procedure of
      preparing the delayed blastocysts demands technical skills. To eliminate
      unnecessary female cells at an initial stage of inner cell mass culture, male
      clones were selected by polymerase chain reaction to detect the mouse Sry gene.
      The established ES cell line efficiently contributed to the germ-line when
      injected into 8-cell embryos of ICR mice. This potency was maintained after
      manipulation throughout gene targeting.

PMID- 8987504
TI  - Chitinase and beta-1,3-glucanase in the lutoid-body fraction of Hevea latex.
AB  - The lutoid-body (bottom) fraction of latex from the rubber tree (Hevea
      brasiliensis) contains a limited number of major proteins. These are, besides the
      chitin-binding protein hevein, its precursor and the C-terminal fragment of this
      precursor, proteins with enzymic activities: three hevamine components, which are
      basic, vacuolar, chitinases with lysozyme activity, and a beta-1,3-glucanase.
      Lutoid-body fractions from three rubber-tree clones differed in their contents of
      these enzyme proteins. The hevamine components and glucanase were isolated and
      several enzymic and structural properties were investigated. These enzymes are
      basic proteins and cause coagulation of the negatively charged rubber particles.
      The coagulation occurs in a rather narrow range of ratios of added protein to
      rubber particles, which indicates that charg neutralization is the determining
      factor. Differences in coagulation of rubber particles by lutoid-body fractions
      from various rubber clones can be explained by their content of hevamine and
      glucanase. Glucanase from the lutoid-body fraction may dissolve callus tissue and
      this may explain the observation that rubber-tree clones with a high glucanase
      content in this fraction produce more latex than clones with little glucanase.
      Sequence studies of two CNBr peptides of the glucanase indicate that this protein
      is homologous with glucanases from other plants, and that a C-terminal peptide,
      possibly involved in vacuolar targeting, may have been cleaved off.

PMID- 8987505
TI  - A putative precursor protein in the evolution of the bean alpha-amylase
      inhibitor.
AB  - Seeds of the common bean Phaseolus vulgaris and the tepary bean (P. acutifolius)
      contain a family of plant defence proteins that includes phytohaemagglutinin
      (PHA), arcelin and alpha-amylase inhibitor (alpha AI). These homologous proteins
      differ by the absence of short loops at the surface of the protein and by the
      presence of a proteolytic processing site (Asn77) that allows alpha AI to be post
      translationally cleaved and activated. We now report the derived amino acid
      sequence of two amylase inhibitor-like (AIL) proteins that are not
      proteolytically processed, although they have the typical processing site. One
      protein is from the common bean, and the other from the tepary bean. On a
      dendrogram, these proteins are grouped with alpha AIs rather than with the
      arcelins or lectins. alpha AI differs from AIL primarily by the deletion of a 15
      amino-acid segment from the middle of the AIL sequence. When alpha AI is
      expressed in tobacco, it is proteolytically processed to form an active molecule.
      However, AIL sequences are not processed. We suggest that the AIL proteins may be
      an intermediate in the evolution of an active alpha AI.

PMID- 8987506
TI  - O-demethylation of 7,7'-epoxylignans by Aspergillus niger.
AB  - Biotransformation of the 7,7'-epoxylignans, (+)-veraguensin, (+)-galbelgin and
      galgravin by Aspergillus niger has been investigated. These lignans were
      converted to their corresponding 4,4'-O-demethyl derivatives, (+)-verrucosin, (+)
      fragransin A2 and nectandrin B.

PMID- 8987507
TI  - Antibiotic phenol nor-triterpenes from Maytenus canariensis.
AB  - The new phenols 6-oxo-tingenol, 3-O-methyl-6-oxo-tingenol and 6-oxo-iguesterol
      were isolated from the root bark of Maytenus canariensis. Their structures were
      determined by 1H and 13C NMR spectroscopic studies, including HMQC, HMBC, DEPT
      and ROESY and chemical transformations. The synthesis of 6-oxo-tingenol was
      achieved from tingenone. These compounds exhibit antibiotic activity against Gram
      positive bacteria.

PMID- 8987508
TI  - Carbazole alkaloids from Clausena excavata and their biological activity.
AB  - Five new carbazole alkaloids, clausines B, E, H, I and K, as well as 22 known
      compounds, were isolated from the stem bark of Clausena excavata. The structures
      were established from spectral data and chemical transformation. These compounds
      showed significant inhibition of rabbit platelet aggregation and caused
      vasocontraction. The crude methanol extract, partitioned layers and
      chromatographic fractions revealed the presence of promotive and inhibitive
      constituents, simultaneously. These results might explain the philosophy of use
      in Chinese medicine, in that the dose and content variation in a prescription
      produced different, promotive or inhibitive, effects on therapy.

PMID- 8987509
TI  - Absolute configuration of octanol derivatives in apple fruits.
AB  - In extracts obtained by liquid-liquid extraction and enzymatic hydrolysis from
      five apple cultivars (Renao; Bedan; Peau de Chien; Noel des Champs; Red
      Delicious), chiral evaluation of free and glycosidically-bound octane-1,3-diol
      and 5(Z)-octene-1,3-diol, as well as ethyl 3-hydroxyoctanoate and ethyl 5(Z)-3
      hydroxyoctenoate, was performed by multidimensional gas chromatography (MDGC),
      combining a polar achiral column (DB-Wax) with a chiral main column (2,3-di-O
      acetyl-6-O-tert. butyldimethylsilyl-beta-cyclodextrin/OV 1701). Comparison of
      retention times of synthesized optically-enriched reference compounds with
      isolated diols and hydroxyesters, revealed the (R)-configuration for the free
      diols in cvs. Renao, Bedan, Peau de Chien and Noel des Champs and the (R)
      configuration for the bound diols in cvs Bedan, Peau de Chien and Noel des
      Champs, exhibiting enantiomeric excesses (ees) greater than 99%. (R)
      hydroxyesters (ee > 99%) were detected in cvs. Noel des Champs and Red Delicious.

PMID- 8987510
TI  - 2,5-Dimethyl-4-hydroxy-3[2H]-furanone 6'O-malonyl-beta-D-glucopyranoside in
      strawberry fruits.
AB  - 2,5-Dimethyl-4-hydroxy-3[2H]-furanone 6'-O-malonyl-beta-D-glucopyranoside was
      isolated from a glycosidic extract of strawberry fruit (Fragaria x ananassa, cv.
      Senga Sengana) by means of countercurrent chromatography and reverse-phase HPLC.
      Identification was achieved by comparison of chromatographic and 1H, 13C and 2D
      NMR, as well as mass spectral data with those of the synthesized reference
      compound. In ripe strawberry fruit, a 1:1 ratio of the malonylated glucoside to
      its deacylated glucoconjugate was determined by on-line liquid chromatography
      atmospheric pressure chemical ionization-tandem mass spectrometry.

PMID- 8987512
TI  - Triterpenoidal saponin glycosides from Glinus lotoides var dictamnoides.

PMID- 8987511
TI  - Dinormonoterpenoids and their apiosylglucosides from Thevetia peruviana.

PMID- 8987513
TI  - Saponins from Pisonia umbellifera.
AB  - Six saponins were isolated from the leaves of Pisonia umbellifera. Three are new
      oleanolic acid saponins, and two of them contain an unusual seco-glycopyranosyl
      moiety. Their structures were determined using a combination of 1H and 13C NMR,
      and mass spectrometry as 3-O-{beta-D-glucopyranosyl(1-->2)[beta-D-glucopyranosyl
      (1-->2)-beta-D-xylopyranosyl(1-->3)]-beta-D-glucuronopyranosyl} 28-O-beta-D
      glucopyranosyl olean-12-en-3 beta-ol-28-oic acid, 3-O-{2'-(2"-O-glycolyl)
      glyoxylyl-beta-D-glucuronopyranos yl} 28-O-beta-D-glucopyranosyl olean-12-en-3
      beta-ol-28-oic acid and 3-O-{2'-O-glycolyl)-glyoxylyl-beta-D-glucuronopyranosyl++
      +} olean-12-en-3 beta-ol-28-oic acid.

PMID- 8987515
TI  - Steroidal glycosides from the subterranean parts of Liriope spicata var.
      prolifera.
AB  - In a continuation of phytochemical studies on the underground organs of Liriope
      spicata var. prolifera, four new steroidal glycosides, lirioproliosides A-D,
      along with two known compounds, 25(S)-ruscogenin 1-O-[alpha-L-rhamnopyranosyl(1-
      >2)[beta-D-xylopyranosyl (1-->3)]-beta-D-fucopyranoside and ophiopogonin A, were
      identified. The structures of lirioproliosides A-D were established by a
      combination of spectroscopic and chemical methods as 25(S)-ruscogenin 1-O-[alpha
      L-rhamnopyranosyl(1-->2)][beta-D-xylopyranosyl (1-->3)]-beta-D-fucopyranoside-3-O
      alpha-L-rhamnopyranoside, 25(S)-ruscogenin 1-O-[3-O-acetyl-alpha-L
      rhamnopyranosyl(1-->2)]-beta-D-fucopyranoside, 25(S)-ruscogenin (1-O-[2-O-acetyl
      alpha-L-rhamnopyranosyl (1-->2)]-beta-D-fucopyranoside and ruscogenin (1-O-[2-O
      acetyl-alpha-L-rhamnopyranosyl(1-->2)]-beta-D-fucopyranoside, respectively. Among
      these steroidal glycosides, ophiopogonin A and lirioprolioside B, and
      lirioproliosides C and D, were isolated as epimeric pairs.

PMID- 8987514
TI  - An echinocystic acid saponin derivative from Kalimeris shimadae.
AB  - A new triterpene saponin, shimadoside A, has been isolated from Kalimeris
      shimadae and its structure deduced as 3-O-beta-D-glucopyranosiduronic acid-3
      beta, 16 alpha-dihydroxyolean-12-en-28-oic acid-28-O-beta-D-xylopyranosyl-(1-->3)
      beta-D-xylopyranosyl-(1--> 4)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D
      xylopyranoside by means of spectral data, especially NMR, including COSY, HMQC,
      HOHAHA and ROESY techniques, and chemical degradation.

PMID- 8987516
TI  - Ruakuric acid: a natural product from Aspergillus fumigatus.
AB  - A new chroman derivative, named ruakuric acid, was isolated from a strain of
      Aspergillus fumigatus growing in conjunction with a coral lichen. The structure
      was determined as 6-acetyl-5-hydroxy-4-methoxy-chroman-2-carboxylic acid (mixture
      of 2,4-cis,trans isomers).

PMID- 8987517
TI  - Teixidol, an abeo-taxane from European yew, Taxus baccata.
AB  - A new taxoid, teixidol, was isolated from the leaves of Taxus baccata. Its
      structure, which features an 11(15-->1)abeo-taxane skeleton consisting of a 5/7/6
      membered ring system, was established by spectroscopic analysis.

PMID- 8987518
TI  - Studies on the hatching enzyme (choriolysin) and its substrate, egg envelope,
      constructed of the precursors (choriogenins) in Oryzias latipes: a sequel to the
      information in 1991/1992.
AB  - Enzymatic hatching of fish embryos is caused by a sequential occurrence of many
      elementary processes from the commitment of the hatching gland cells to the
      emergence of the embryos. Molecular biological approaches to the formation,
      properties and function of the hatching enzyme should be required for elucidation
      of the enzymatic hatching, since this enzyme is a key molecule to analyze these
      processes. Besides them, there are some other processes indirectly related to
      hatching, e.g., formation and hardening of the egg envelope. The present article
      describes the results of our studies on some of the above-mentioned problems in
      the fish, Oryzias latipes, which have been obtained mostly in the early 1990s.

PMID- 8987519
TI  - Effects of eel neuropeptide Y on ion transport across the seawater eel intestine.
AB  - A neuropeptide Y (eNPY) was isolated from the intestinal extract of eels. This
      peptide enhanced significantly the serosa-negative transepithelial potential
      difference (PD) and short-circuit current (Isc) across the intestine of the
      seawater eel after pretreatment with isobutylmethylxanthine, serotonin and
      methacholine. The effects of eNPY on the Isc were concentration-dependent with a
      threshold concentration of 3 x 10(-9) M and a maximal effect at 3 x 10(-7) M.
      Similar concentration-response curve was obtained by porcine peptide YY (pPYY).
      Since 9 amino acid residues are replaced in the pPYY, this result indicates that
      these substitutions do not change the potency and the efficacy. These stimulatory
      actions of eNPY were not blocked by tetrodotoxin, an inhibitor of neural firing,
      or yohimbine, an alpha 2-adrenoceptor antagonist, indicating that eNPY acts
      without enteric neural firing or catecholamine release. When eNPY and adrenaline
      (AD) were applied simultaneously, the effects were additive only at lower dosage
      (3 x 10(-8) M for eNPY, 3 x 10(-8) M for AD), but not at high dosage (10(-6) M
      eNPY, 10(-7) M AD). The ceiling effect at high dosage suggests that these two
      regulators act through common signal transduction systems and affect the Na(+)
      K(+)-Cl- cotransport system, since both effects were completely blocked by
      bumetanide, a specific inhibitor of Na(+)-K(+)-Cl- cotransporter.

PMID- 8987520
TI  - Characterization of novel metallo-proteases released from ascidian hemocytes by
      treatment with calcium ionophore.
AB  - We have previously demonstrated that calcium ionophore induced the release of a
      novel metallo-protease from hemocytes of a solitary ascidian, Halocynthia
      roretzi. Here, we isolated the enzymes, PI and PII, from the culture media of H.
      roretzi hemocytes, which had been treated with calcium ionophore, A23187. The
      purification procedure included hydrophobic and anion-exchange chromatographies,
      and gel filtration. The molecular weights of the enzymes were estimated to be
      11,000 by gel filtration, but the apparent sedimentation coefficients were 5.0 S,
      which suggests that the H. roretzi enzymes are of larger proteins with molecular
      weights of 80,000-90,000. The most susceptible substrate was succinyl-Leu-Leu-Val
      Tyr-4-methylcoumaryl-7-amide, and the optimum pH was 8.0, in either case of PI or
      PII. The activities of PI and PII enzymes were strongly inhibited by metal
      chelating agents and propioxatin A, but not by phosphoramidon, a typical metallo
      protease inhibitor. Zinc and calcium ions were found to be essential for the
      maximum expression of protease activity in both enzymes. Thus, the isolated
      enzymes are characterized as phosphoramidon-insensitive metallo-proteases, which
      are inhibited by propioxatin A. Extracellular roles of these enzymes were also
      discussed.

PMID- 8987521
TI  - Two types of cDNAs encoding proopiomelanocortin of sockeye salmon, Oncorhynchus
      nerka.
AB  - To investigate regulatory mechanisms of proopiomelanocortin (POMC) gene
      expression in sockeye salmon, we have isolated and characterized cDNAs encoding
      two types of sockeye salmon POMC, which are referred to as ssPOMC-A and -B. Two
      types of PCR products were amplified from total RNA of sockeye salmon pituitaries
      by use of rainbow trout sequences. Full length cDNA clones encoding ssPOMC-A and
      ssPOMC-B were obtained from a pituitary cDNA library of sockeye salmon using the
      PCR products as probes. The ssPOMC-A and -B cDNAs have a length of 1072 and 1709
      bps, respectively. Northern blot analysis showed that both ssPOMC-A and -B mRNAs
      were expressed only in the pituitary, and their sizes were about 1.2 kb and 1.8
      kb, respectively. The presence of two ssPOMC genes was confirmed by Southern blot
      analysis of genomic DNA obtained from a single sockeye salmon. The deduced amino
      acid sequences of the ssPOMC-A and -B contained 230 and 226 residues,
      respectively. The amino terminal of beta-endorphin in ssPOMC-B which corresponds
      to Met-enkephalin domain is YSGFM, which is different from YGGFM of Met
      enkephalin found in many other vertebrate species. The homology of nucleotide
      sequences between ssPOMC-A and -B is 59% in the entire coding region, whereas
      alpha-MSH coding regions are highly homologous (91%). Although the deduced amino
      acid sequences of ssPOMs show 43% overall similarity, their hydropathy profiles
      are coincident with those of several other vertebrate species, particularly the
      amino terminal of N-terminal peptide (NPP) shows almost the same pattern with
      other vertebrate NPPs.

PMID- 8987522
TI  - Modification of prolactin receptor (PRL-R) expression by PRL in the mouse liver:
      estimation of the ratio of two forms of PRL-R mRNAs by "one-sided competitive
      PCR".
AB  - We developed new means of measuring the ratio of the short to the long form (S/L
      ratio) of the mouse prolactin receptor (mPRL-R) cDNA by PCR using a primer common
      to the two forms and two specific primers. A means of estimating the amount of
      mPRL-R cDNA by competitive PCR was also established. We confirmed that these
      procedures were valid, since the S/L ratio of standard DNA was unaltered by one
      sided cPCR amplification under the following conditions: the ratio was between
      0.1 and 4, and the amount of cDNA was between 10(3) and 10(7) molecules/tube. The
      result of one-sided cPCR showed that the short form was dominant in the mouse
      liver, while the long form was dominant in other tissues. In addition, pituitary
      grafting increased the S/L ratio in the liver, implying that prolactin down
      regulated the functional long form of PRL-R and lowered tissue sensitivity to
      prolactin itself by modifying the post-transcriptional regulation of PRL-R.

PMID- 8987523
TI  - Homeobox genes exhibit evolutionary conserved regionalization in the central
      nervous system of an ascidian larva.
AB  - Animals in each subgroup of the phylum Chordata exhibit a similar process by
      which they form a tubular central nervous system (CNS). However, little is known
      about spatial relationship among the CNSs of chordates; vertebrates,
      cephalochordates and urochordates (tunicates). Ascidians constitute a major
      animal group in the subphylum Urochordata. In the present study, we examined the
      expression patterns of labial and orthodenticle related genes of the ascidian,
      Halocynthia roretzi, in the developing larval CNS. These homeobox genes exhibited
      region-specific expression patterns that are strikingly similar to those of
      murine Hoxb-1 and Otx2. The regionalization as characterized by the expression of
      these genes supports the division of the ascidian larval CNS suggested by the
      previous morphological studies. Furthermore, conservation of the expression
      pattern of the homeobox genes suggests that such regionalization occurred in the
      CNS of a putative common ancestor of chordates.

PMID- 8987524
TI  - Glycoproteins: a consideration of the potential problems and their solutions with
      respect to purification and characterisation.
AB  - Glycoproteins, as a class of biomolecules, present a number of differences in
      structure and function from non-glycosylated proteins. This makes their
      purification and characterisation a potentially daunting prospect. This article
      provides a brief summary of the occurrence, structure and composition of
      glycoproteins and the main areas where these factors may complicate the
      purification and characterisation process. There follows a review of the range of
      techniques available, an insight into the choices of ways forward in considering
      glycoprotein purification and characterisation. Appropriate prominence is given
      to lectins; their application to the purification, identification and
      characterisation of glycoproteins, and the major contribution they have made to
      the study of this class of biomolecules.

PMID- 8987525
TI  - Flocculation of Esch. coli with cationic polymers: a model for the dose curve
      based on charge.
AB  - Continuously grown cells from a glucose limited chemostat were flocculated with
      four different cationic polymers. The polymer was added to the cells either
      dropwise or as a slug at the start of the flocculation period. Dose curves for
      each polymer type and using each method of polymer addition were constructed. It
      was evident that classical overdose was possible with all four polymers if slug
      addition was used. Continuous addition produced dose curves overdose was possible
      with all four polymers if slug addition was used. Continuous addition produced
      dose curves with no overdosing except when low molecular weight, low charge
      density polymer was used. The dose curves could be combined if they were based on
      amount of charge added. The dose curve was not linear, but fitted a logarithmic
      model well. Charge density was much more important than MW of the polymer.

PMID- 8987526
TI  - Affinity purification of cellulose-binding enzymes of Clostridium stercorarium.
AB  - Cellulose-affinity chromatography proved to be a fast and efficient purification
      procedure for exoenzymes of the thermophilic anaerobe Clostridium stercorarium,
      suitable for the preparation of large amounts of enzymes for technical
      applications. The cellulose-binding enzymes could be identified as the C.
      stercorarium; cellulolytic enzymes Avicelase I and Avicelase II characterized
      previously as endo-1,4-beta-glucanase and exo-1,4-beta-glucanase. A third protein
      was identified as xylanase A, the major endo-1,4-beta-xylanase of this organism.

PMID- 8987527
TI  - The effect of thermal deactivation on the properties and processing
      characteristics of E. coli.
AB  - Recombinant microorganisms are often employed to produce proteins of commercial
      significance. It is important to render such organisms non-viable before culture
      fluids are released from the fermenter. Thermal deactivation is a superficially
      attractive option because of its simplicity. The effects of such a thermal
      deactivation step at the end of a recombinant fermentation are reported in this
      study. In particular, the consequences of this treatment for down-stream process
      operations, namely homogenisation and centrifugation, are analysed and discussed.
      Homogenisation efficiency was adversely affected by a simple treatment whereby
      cells are raised to 65 degrees C from stationary phase. Cell debris size was also
      significantly increased. These changes could be partially explained by an
      increase in fractional peptidoglycan crosslinkage and a decrease in mean cell
      length. A simple process modification removed these detrimental effects.
      Specifically, the addition of 15 g of glucose 15 mins prior to thermal
      deactivation enhances downstream processing. Disruption efficiency is increased
      above that for stationary-phase cells and the resultant cell debris size is
      significantly reduced, theoretically aiding inclusion body purification. This
      novel process modification demonstrates that thermal deactivation may be employed
      to prevent the release of viable recombinant organisms while providing a broth
      with desirable processing characteristics. It also emphasises the need to
      optimise any bioprocess as an interconnected sequence of units.

PMID- 8987528
TI  - Alternative regulation principles for the production of recombinant proteins in
      Escherichia coli.
AB  - Established expression vectors exploiting regulated promoters such as the lac or
      tac promoters have economic and technical limitations when used for the
      industrial production of recombinant proteins. Consequently, alternative
      expression systems are being developed that can be more readily manipulated while
      maintaining high yields of protein. Several suitable expression vectors have been
      described for use in Escherichia coli that are based on promoters the activity of
      which is under metabolic control. This article discusses the advantages and
      disadvantages of a cross-section of these expression systems, how they compare
      with established systems and how they can be applied to the industrial-scale
      production of recombinant proteins.

PMID- 8987529
TI  - Disposable sensor for biochemical oxygen demand.
AB  - Disposable-type microbial sensors were prepared for the determination of
      biochemical oxygen demand (BOD). The yeast, Trichosporon cutaneum, was directly
      immobilized on the surface of miniature oxygen electrodes using an ultraviolet
      crosslinking resin (ENT-3400). The oxygen electrodes (15 mm x 2 mm x 0.4 mm) were
      made on silicon substrates using micromachining techniques. They were Clark-type
      two-electrode systems with-1021 mV applied to the working electrode. Typical
      response times of the BOD sensors were in the range of 7-20 min. At 20 degrees C,
      the sensors' dynamic range was from 0 to 18 mg/1 BOD when a glucose/glutamate BOD
      standard solution was used. The lower limit of detection was 0.2 mg/l BOD. This
      value was one order of magnitude lower than that of sensors previously reported.
      The sensors' operational lifetime of 3 days was satisfactory for a disposable
      type. The sensors' responses were reproducible to within 8% relative standard
      deviation. The BOD sensors' were applied to untreated and treated waste waters
      from industrial effluents and municipal sewage. BOD values determined using these
      sensors correlated well with those determined by the conventional 5-day BOD
      determination method.

PMID- 8987531
TI  - The effect of cations on the hydrolysis of lactose and the transferase reactions
      catalysed by beta-galactosidase from six strains of lactic acid bacteria.
AB  - beta-Galactosidases from Lactobacillus delbruekii subsp. bulgaricus 20056, Lb.
      casei 20094, Lactococcus lactis subsp. lactis 7962, Streptococcus thermophilus
      TS2, Pediococcus pentosaceus PE39 and Bifidobacterium bifidum 1901 were partially
      purified. The rate of hydrolysis of lactose given by the predominant beta
      galactosidase activity from each of the bacteria studied was in all cases
      enhanced by Mg2+, while the effect of K+ and Na+ differed from strain to strain.
      The beta-galactosidases from all strains also catalysed trans-galactosylation
      reactions. The types of oligosaccharides produced appeared to be very similar in
      each case, but the rates of their production differed. All the beta
      galactosidases were also capable of hydrolysing galactosyl-lactose although,
      unlike the other bacteria studied, Lb. delbruekii subsp. bulgaricus 20056 and Lc.
      lactis subsp. lactis 7962 were unable to utilise galactosyl-lactose as a carbon
      source for growth.

PMID- 8987532
TI  - An expression system based on the promoter region of the Aspergillus awamori 1,4
      beta-endoxylanase A gene.
AB  - A new, highly inducible fungal promoter derived from the Aspergillus awamori 1,4
      beta-endoxylanase A (exlA) gene is described. Induction analysis, carried out
      with the wild-type strain in shake flasks, showed that exlA expression in
      regulated at the transcriptional level. Using a beta-glucuronidase (uidA)
      reporter strategy, D-xylose was shown to be an efficient inducer of the exlA
      promoter, whereas sucrose or maltodextrin were not. Upon D-xylose induction, the
      exlA promoter was threefold more efficient than the frequently used A. niger
      glucoamylase (glaA) promoter under maltodextrin induction. Detailed induction
      analyses demonstrated that induction was dependent on the presence of D-xylose in
      the medium. Carbon-source-limited chemostat cultures with the uidA reporter
      strain showed that D-xylose was also a very good inducer in a fermenter, even in
      the presence of sucrose.

PMID- 8987530
TI  - A mutant trypsin-like enzyme from Streptomyces fradiae, created by site-directed
      mutagenesis, improves affinity chromatography for protein trypsin inhibitors.
AB  - The Ser-170 residue of a trypsin-like enzyme from Streptomyces fradiae (SFT),
      which is considered to be the active-site serine, was replaced with alanine by
      site-directed mutagenesis to improve the affinity chromatography step for a Kazal
      type trypsin inhibitor pancreatic secretory trypsin inhibitor (PSTI). The
      resulting mutant SFT, designated as [S170A]SFT, was expressed in Streptomyces
      lividans and purified to homogeneity. [S170A]SFT was catalytically inactive, but
      still had the ability to bind tightly to PSTI and to soybean trypsin inhibitor
      with dissociation constants of 3.1 x 10(-7) M and 1.9 x 10(-8) M respectively. We
      further demonstrated that recombinant human PSTI secreted into Saccharomyces
      cerevisiae culture broth could be purified to homogeneity with a one-step
      [S170A]SFT-affinity column. The purified PSTI contained no molecules
      intramolecularly cleaved by active trypsin, which are found when trypsin-affinity
      chromatography is used for the purification. This eliminated the need for further
      separation of intact PSTI from intramolecularly cleaved PSTI by high-performance
      liquid chromatography, thus simplifying and improving its purification process.

PMID- 8987533
TI  - Saccharomyces cerevisiae mutants selected for increased production of Trichoderma
      reesei cellulases.
AB  - Trichoderma reesei endoglucanase I (EGI) was used as a reporter enzyme for
      screening mutagenized yeast strains for increased ability to produce protein.
      Sixteen haploid Saccharomyces cerevisiae strains, transformed with a yeast
      multicopy vector pALK222, containing the EGI cDNA under the ADH1 promoter,
      produced EGI activity of 10(-5)-10(-4) g/l. On the average 93% of the total
      activity was secreted into the culture medium. Two strains with opposite mating
      types were mutagenized, and several mutants were isolated possessing up to 45
      fold higher EGI activity. The best mutants were remutagenized and a second
      generation mutant, strain 2804, with an additional twofold increase in EGI
      activity was selected. The mutant strain 2804 grew more slowly and reached a
      lower final cell density than the parental strain. In the selective minimal
      medium, the 2804 strain produced 40 mg/l immunoreactive EGI protein, but only 2%
      was active enzyme. In the rich medium the secreted EGI enzyme stayed active, but
      without selection pressure the EGI production ceased after 2 days of cultivation,
      when the strain 2804 had produced 10 mg/l of EGI. A sevenfold difference was
      found between the parental and the 2804 strain in their total EGI production
      relative to cell density. The difference in favour of the mutant strain was also
      detected on the mRNA level. The 2804 mutant was found to be more active than the
      parental strain also in the production of T. reesei cellulases, cellobiohydrolase
      I, and cellobiohydrolase II.

PMID- 8987534
TI  - Recombinant Hansenula polymorpha as a biocatalyst: coexpression of the spinach
      glycolate oxidase (GO) and the S. cerevisiae catalase T (CTT1) gene.
AB  - The methylotrophic yeast Hansenula polymorpha has been developed as an efficient
      production system for heterologous proteins. The system offers the possibility to
      cointegrate heterologous genes in anticipated fixed copy numbers into the
      chromosome. As a consequence co-production of different proteins in
      stoichiometric ratios can be envisaged. This provides options to design this
      yeast as an industrial biocatalyst in procedures where several enzymes are
      required for the efficient conversion of a given inexpensive compound into a
      valuable product. To this end recombinant strains have been engineered with
      multiple copies of expression cassettes containing the glycolate oxidase (GO)
      gene from spinach and the catalase T (CTT1) gene from S. cerevisiae. The newly
      created strains produce high levels of the peroxisomal glycolate oxidase and the
      cytosolic catalase T. The strains efficiently convert glycolate into glyoxylic
      acid, oxidizing the added substrate and decomposing the peroxide formed during
      this reaction into water and oxygen.

PMID- 8987535
TI  - Pulse-field gel-electrophoretic analysis of the amplification and copy-number
      stability of an integrational plasmid in Bacillus subtilis.
AB  - The stability of integration and amplification of an integrational plasmid in
      Bacillus subtilis was analyzed. A cat-containing plasmid was constructed that
      could be integrated into the amy locus to facilitate measurement of excision
      events. Pulse-field gel electrophoresis was used to measure the copy number in
      strains that were resistant to different levels of chloramphenicol. The stability
      of the amplified unit in strains containing from 2 to 18 tandem copies of the
      amplicon in the presence and absence of chloramphenicol and through different
      generation times was then determined. Our results demonstrate that, for any given
      strain, the copy number of the amplicon remains stable. Furthermore, this
      stability is maintained when a clone containing an amplicon of defined size is
      cultured through as many as 100 generations in the absence of selective pressure.

PMID- 8987536
TI  - IS431mec-mediated integration of a bleomycin-resistance gene into the chromosome
      of a methicillin-resistant Staphylococcus aureus strain isolated in Japan.
AB  - A methicillin-resistant Staphylococcus aureus (MRSA) strain B-26, isolated
      clinically in Hiroshima University Hospital, is resistant to bleomycin together
      with kanamycin. In the present study, we analysed the nucleotide sequence of the
      5.1-kb HindIII fragment containing the bleomycin- and kanamycin-resistance genes,
      which were previously cloned [Bhuiyan et al. (1995) Appl Microbiol Biotechnol 43:
      65-69] from the chromosomal DNA of MRSA B-26. The present study found that the
      DNA sequence contains the duplicated target sequence (GATTAGAT) consisting of 8
      bp for transposase and the entire nucleotide sequence of the plasmid pUB110,
      together with the sequence of inverted repeats (16 bp), designated IR-r and IR-1
      in IS431 mec. The 8-bp duplication sequence, produced by the transposable
      element, was first found by us. We proposed that bleomycin resistance in MRSA B
      26 is attributed to the IS431 mec-mediated integration of pUB110 into the
      chromosome.

PMID- 8987537
TI  - Initial steps of sophoroselipid biosynthesis by Candida bombicola ATCC 22214
      grown on glucose.
AB  - Candida bombicola ATCC 22214 produces the glycolipid sophoroselipid when
      cultivated on a medium with glucose as the sole carbon source. Under phosphate
      limiting conditions the product yield rises from 0.033 to 0.143 and the specific
      product formation rate rises from 0.004 h-1 to 0.007 h-1. Enhanced sophoroselipid
      synthesis is initiated by the decline of the specific activities of NAD- and NADP
      dependent isocitrate dehydrogenase (EC 1.1.1.41 and 1.1.1.42) to 2% and 0% of the
      initial activities respectively. Constantly high specific activity of citrate
      synthase (EC 4.1.3.7) causes an accumulation of isocitrate and citrate in the
      mitochondria. Both acids are transported into the cytosol where citrate is
      cleaved by ATP: citrate lyase (EC 4.1.3.8) giving rise to acetyl-CoA, the
      precursor of fatty acid synthesis. The ATP: citrate lyase is unaffected by
      different energy charges; the apparent K(m) values for coenzyme A, ATP and
      citrate are 23 microM, 250 microM and 256 microM respectively. NADPH for fatty
      acid synthesis might be generated by further metabolism of oxaloacetate, the
      other product of the citrate-cleaving reaction, by oxidation of the isocitrate by
      the cytosolic NADP-dependent isocitrate dehydrogenase or via the hexose
      monophosphate shunt. A possible explanation for sophoroselipid formation during
      exponential growth is given.

PMID- 8987538
TI  - Comparison of the properties of native and pentaammineruthenium(III)-modified
      xylanase.
AB  - Two xylanases, xynA of Bacillus pumilus and xyn II of Trichoderma reesei, were
      purified and then modified by the attachment of pentaammineruthenium, thereby
      resulting in the generation of a xylanase with veratryl alcohol oxidase activity.
      Hydrolytic activity of T. reesei xyn II on soluble xylans was unchanged by
      modification with pentaammineruthenium; however, modification of B. pumilus xynA
      greatly reduced xylan hydrolysis unless the active site of the xylanase was
      protected with xylose during the modification. The presence of histidine,
      cysteine, or reduced glutathione during xylan hydrolysis greatly increased the
      xylanase activity of the pentaammineruthenium-modified B. pumilus xylanase.
      Glycine, glutamic acid, methionine, or oxidized glutathione had no effect on
      xylanase activity.

PMID- 8987539
TI  - Rice allergenic protein and molecular-genetic approach for hypoallergenic rice.
AB  - Allergenic proteins with a molecular mass of about 14 to 16 kDa were isolated
      from a rice salt-soluble fraction based on the reactivity with IgE antibodies
      from patients allergic to rice. cDNA clones encoding these allergenic proteins
      were isolated from a cDNA library of maturing rice seeds, and the deduced amino
      acid sequences showed considerable similarity to wheat and barley alpha
      amylase/trypsin inhibitors, which have recently been identified as major
      allergens associated with baker's asthma. An antisense RNA strategy was applied
      to repress the allergen gene expression in maturing rice seeds. Immunoblotting
      and ELISA analyses of the seeds using a monoclonal antibody to a 16-kDa allergen
      showed that allergen content of seeds from several transgenic rice plants was
      markedly lower than that of the seeds from parental wild type rice.

PMID- 8987540
TI  - Cloning, sequencing, and expression of a beta-amylase gene from Bacillus cereus
      var. mycoides and characterization of its products.
AB  - The cloned gene was composed of 1638 bp for coding plus promoter like and SD-like
      sequences ahead of it. The deduced amino acid sequence had high similarity with
      known beta-amylases. The N-terminal sequence of the cloned beta-amylase seemed to
      be a signal peptide. The gene was introduced into Bacillus subtilis 1A289 using
      pHY300PLK as a vector and the expressed protein was recovered from the culture
      media. The enzyme fraction produced was divided into two components upon the DEAE
      column chromatography. The amino acid sequence of one fraction (FrI) was the same
      as the mature enzyme, and the other (FrII) lacked the N-terminal amino acid
      residue (Ala) of the mature enzyme. The kinetic parameters of the hydrolysis
      catalyzed by the enzyme component FrI were measured, and the subsite affinities
      of the enzyme were evaluated. In conclusion, it was shown that the recombinant
      enzyme was the same as the mature enzyme functionally and proteochemically.

PMID- 8987541
TI  - Modification of wheat flour with bromelain and baking hypoallergenic bread with
      added ingredients.
AB  - Based on the wheat glutenin IgE-binding epitope, Gln-Gln-Gln-Pro-Pro, a practical
      method is proposed for the production of hypoallergenic wheat flour. Bromelain
      was found effective for decomposing the epitope structure. In practice, soft
      flour was mixed with water dissolving bromelain and the mixture was incubated at
      37 degrees C for 4 h. The result of IgE-ELISA (enzyme-linked immunosorbent assay)
      suggested negative allergenicity. A mixture of bromelain-modified flour, glucose,
      citric, acid, a surfactant and sodium hydrogen carbonate was baked to produce
      hypoallergenic bread, resembling English muffins.

PMID- 8987542
TI  - Purification and properties of tyrosinase isozymes from the gill of Lentinus
      edodes fruiting body.
AB  - Six tyrosinase isozymes were purified from the browned gill of the fruiting body
      of Lentinus edodes by ammonium sulfate fractionation, DEAE-Sephacel and Q
      Sepharose column chromatography, and partially denaturing SDS-PAGE. At the step
      of Q-Sepharose column chromatography, two active fractions (A and B) were
      obtained. Each fraction was separated to three further fractions, A1, A2, and A3,
      and B1, B2, and B3, respectively, by partially denaturing SDS-PAGE. All these
      isozymes consisted of two types of polypeptides: alpha polypeptide (A alpha or B
      alpha) and either beta (A beta or B beta) or gamma polypeptide (A gamma or B
      gamma). The alpha polypeptide contained the consensus amino acid sequence of the
      active site of known tyrosinases, which is considered to act as a catalytic
      subunit. From the results of peptide mapping and the amino acid composition, A
      alpha and B alpha polypeptides were considered to be different proteins. The
      kinetic properties of the purified tyrosinase isozymes differed greatly according
      to whether they contained beta or gamma polypeptide, indicating these
      polypeptides to be a possible regulatory subunit.

PMID- 8987543
TI  - Conversion of a cyanhydrin compound into S-(-)-3-phenyllactic acid by
      enantioselective hydrolytic activity of Pseudomonas sp. BC-18.
AB  - A Pseudomonas strain, named BC-18, which can convert racemic phenylacetaldehyde
      cyanhydrin (3-phenyllactonitrile) enantioselectively to S-(-)-3-phenyllactic acid
      (S-PLA), was isolated from soil. Although PLA produced with intact cells
      contained the S enantiomers of approximately 75% enantiomeric excess (% e.e.),
      repeated crystallization gave a higher purity (99.8% e.e.) of the S configuration
      product. Production of S-PLA was significantly increased when 2.0% (w/v) of
      calcium chloride were added to the reaction mixture for precipitation of S-PLA.
      Chemical mutagenesis yielded a mutant strain, named BC348-9, with 16 times higher
      activity (40 mU/OD630), compared with that of the parent strain (2.5 mU/OD630).
      When the mutant strain BC348-9 was used, approximately 18 g/OD630 was produced,
      which is 12 times higher than that of the parent strain. The final accumulation
      of PLA exceeded 6.0%, 1.2 times higher than that of the parent strain.

PMID- 8987544
TI  - Cloning and sequence analysis of a protease-encoding gene from the marine
      bacterium Alteromonas sp. strain O-7.
AB  - The gene (aprI) encoding alkaline serine protease (AprI; subtilase) from
      Alteromonas sp. strain O-7 was cloned and sequenced. The nucleotide sequence of
      aprI has been identified. The deduced amino acid sequence indicated that aprI
      codes for a precursor of 715 amino acids and the precursor is composed of four
      regions including a signal peptide, an N-terminal pro-region, a mature protease
      region and a C-terminal extension region of 215 amino acids as previously
      described for aprII [H. Tsujibo et al., Gene, 136, 247-251 (1993)]. The amino
      acid sequence of the mature AprI (AprI-M) showed high sequence homology with
      those of other class I subtilases. The C-terminal region was characterized by a
      repeat of 94 amino acids residues, which showed about 50% similarity with those
      of the C-terminal pro-region of several known proteases from Gram-negative
      bacteria.

PMID- 8987545
TI  - Mercuric ion uptake by Escherichia coli cells producing Thiobacillus ferrooxidans
      merC.
AB  - The merC gene of Thiobacillus ferrooxidans was overexpressed in Escherichia coli
      under the control of the tac promoter. MerC protein synthesized in E. coli has a
      N-terminal amino acid sequence of S-A-I-X-R-I-I-D-K-I-G-I-V-G-, which agrees with
      the amino acid sequence deduced from its nucleotide sequence except that an
      initiating methionine residue was removed. The MerC protein was localized in the
      particulate (membrane) cell fraction, and not in the soluble cytoplasmic
      fraction. E. coli cells carrying a plasmid containing the tac promoter-directed
      merC showed 203Hg2+ uptake in an isopropyl-1-thio-beta-D-galactopyranoside (IPTG)
      dependent manner.

PMID- 8987546
TI  - Lymphatic absorption of seal and fish oils and their effect on lipid metabolism
      and eicosanoid production in rats.
AB  - Eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) were distributed mainly in
      the sn-1 and 3 positions of seal oil triglyceride and in the sn-2 position of
      fish oil triglyceride. In Expt. 1, the structural distribution of EPA and DHA in
      lymph triglyceride of rats given seal or fish oils was similar to the
      distribution in the administered oils. In Expt. 2, seal oil-rich or fish oil-rich
      fats having constant polyunsaturated/monounsaturated/saturated fatty acids and n
      6/n-3 polyunsaturated fatty acids ratios were fed to rats for 3 weeks. Seal oil
      more effectively reduced plasma and liver triglyceride than fish oil. Ratio of
      the productions of aortic prostacyclin and platelet thromboxane A2 stimulated by
      thrombin was significantly higher in rats fed seal oil than in those fed fish
      oil. The results suggested that the different intramolecular distribution of EPA
      and DHA in dietary fat affected lipid metabolism differently in rats.

PMID- 8987547
TI  - Soluble egg shell membrane protein as a regulating material for collagen matrix
      reconstruction.
AB  - Soluble egg shell membrane protein (SEP) was prepared from egg shell membrane by
      the combined treatment of performic acid oxidation (4 or 25 degrees C for 24 h)
      and pepsin digestion (25 degrees C for 24-72 h) before dialyzing against water
      and lyophilizing. The yield of SEP was about 16-39%. SEP had high contents of
      acidic amino acids (320-340 residues/1000 residues) containing cysteic acid (101
      108 residues) converted from cystine, a small amount of saccharides, a main
      molecular weight of 12,000-22,000 and pI 4.2-4.8. SEP accelerated the
      reconstruction of collagen matrix with ordered molecular rearrangement and
      reduced redissolution of the collagen matrix under several solvent conditions.
      SEP elevated the denaturation temperature of the matrix.

PMID- 8987548
TI  - The phylogeny of species of the genus Saccharomycopsis Schionning
      (Saccharomycetaceae) based on the partial sequences of 18S and 26S ribosomal
      RNAs.
AB  - Eight strains of Saccharomycopsis species were examined for their partial base
      sequences of 18S and 26S rRNAs. The base sequences on the fingerprint segment
      showed three kinds of ACUAU, UCUAU, and AUAU. In the partial base sequences
      (positions 1451-1618, 168 bases) of 18S rRNA, all the strains of Saccharomycopsis
      species examined had 1-0 base difference except for the strains of
      Saccharomycopsis fibuligera (base differences, 5-4). In the partial base
      sequences on the positions 1611-1835 region (225 bases) of 26S rRNA, however,
      S'copsis vini had 15-11 base differences. The other species had 7-2 base
      differences. In the partial base sequences on the positions 493-622 region (130
      bases) of 26S rRNA, the calculated percent similarities were 62-77. Discussion
      was made phylogenetically and taxonomically, especially on the separation of
      S'copsis fibuligera (identical to Endomyces fibuliger) from the genus
      Saccharomycopsis.

PMID- 8987549
TI  - Design and synthesis of gentiohexaosyl derivatives for an ANP receptor
      antagonist, HS-142-1.
AB  - A hexaosyl fragment of the major component of lipooligosaccharide HS-142-1, O-(3
      O-caproyl-beta-D-glucopyranosyl)-(1-->6)-[O-(beta-D- glucopyranosyl)-(1-->6)-O-(3
      O-caproyl-beta-D-glucopyranosyl)-(1--> 6)]2-D-glucopyranose (1), was efficiently
      synthesized by block synthesis. More stable analogs, O-(3-O-hexyl-beta-D
      glucopyranosyl)-(1-->6)-[O-(beta-D-glucopyranosyl)- (1-->6)-O-(3-O-hexyl-beta-D
      glucopyranosyl)-(1-->6)]2-D-glucopyranose (4) and O-(3-O-caproyl-2,4,6-tri-O
      methyl-beta-D-glucopyranosyl)-(1-->6)-[O- (2,3,4-tri-O-methyl-beta-D
      glucopyranosyl)-(1-->6)-O-(3-O-caproyl-2,4-di -O- methyl-beta-D-glucopyranosyl)
      (1-->6)]2-2,3,4-tri-O-methyl-D-glucopyrano se (2), were also designed and
      synthesized in a similar manner.

PMID- 8987550
TI  - Evidence for the interaction between (-)-epigallocatechin gallate and human
      plasma proteins fibronectin, fibrinogen, and histidine-rich glycoprotein.
AB  - Human plasma proteins were subjected to affinity chromatography with (-)
      epigallocatechin gallate (EGCg)-agarose, and the bound proteins were examined by
      sodium dodecylsulfate-polyacrylamide gel electrophoresis. A molecular weight
      evaluation of the protein bands suggested the presence of three proteins,
      fibronectin, fibrinogen, and a 75-kDa protein. When human serum was used, the 75
      kDa protein dominated the bound fraction. The determination of the partial amino
      acid sequence of a peptide derived by endopeptidase digestion of this fraction
      suggested the 75-kDa protein to be histidine-rich glycoprotein (HRG). The
      presence of these proteins in the bound fraction was confirmed by the
      immunoblotting method. Affinity chromatography of the individual proteins
      indicated that fibrinogen and HRG had direct affinity for EGCg. Dot binding
      assays demonstrated the interaction of EGCg with these proteins. The method also
      showed that only gallate-containing catechins were bound by these proteins. These
      data suggest that when EGCg is absorbed in the body through the digestive system,
      it may interact with these proteins in blood plasma.

PMID- 8987551
TI  - Purification and characterization of N-acetylglucosamine 6-phosphate deacetylase
      with activity against N-acetylglucosamine from Vibrio cholerae non-O1.
AB  - An enzyme that deacetylates N-acetylglucosamine to glucosamine from Vibrio
      cholerae non-O1 was purified to homogeneity by sequential procedures. The native
      enzyme had a molecular mass of 190,000 Da and was predicted to be composed of
      four identical subunits with molecular masses of 45,000 Da. The purified enzyme
      hydrolyzed N-acetylglucosamine, N-acetylglucosamine 6-phosphate, and N
      acetylglucosamine 6-sulfate, but not chitin oligosaccharides, and N
      acetylgalactosamine. The deacetylase activity was completely abolished by N
      ethylmaleimide, p-chloromercuribenzoate, EDTA, and Cu2+. On the other hand, the
      activity was activated by Co2+. The amino-terminal amino acids of the purified
      enzyme were sequenced. Among the 22 N-terminal amino acid residues, 12 residues
      of Vibrio deacetylase were identical with that of Escherichia coli GlcNAc 6
      phosphate deacetylase.

PMID- 8987552
TI  - Purification of membrane-bound ATPase of a psychrophilic marine bacterium, Vibrio
      sp. strain ABE-1 and characterization as a F0F1-type enzyme.
AB  - The ATPase bound to the inner membrane of a psychrophilic marine bacterium,
      Vibrio sp. strain ABE-1 (Vibrio ABE-1) was extracted with Triton X-100 and
      purified by fractionation with polyethylene glycol, sucrose density gradient
      centrifugation, and DEAE-Toyopearl 650M column chromatography. The molecular
      masses of subunits constituting the purified ATPase were estimated as 54, 49,
      33.5, 27, 23.5, 18.5, and 15 kDa by SDS-PAGE. The composition and molecular
      masses of the subunits of the purified ATPase were similar to those of
      Escherichia coli F0F1-ATPase (EF0F1). The 54-, 49-, and 18.5-kDa polypeptides of
      the Vibrio ABE-1 ATPase strongly cross-reacted with the antibodies against the
      EF0F1 alpha, beta, and b subunits, respectively. However, the Vibrio ABE-1 ATPase
      contained no cross-reactive polypeptide with the antibodies against A and B
      subunits of V-type H(+)-ATPase from mung bean tonoplasts. The ATPase activity
      showed two pH optimum peaks at pH 5.3 and 8.0 and was strongly inhibited by N,N'
      dicyclohexyl carbodiimide (DCCD) and NaN3. It hydrolyzed ATP, GTP, and ITP at
      similar rates. These properties confirm that the purified ATPase is a F0F1-type.
      The optimum temperature for the ATP-hydrolyzing activity of the enzyme was
      observed at 50 degrees C, but the DCCD-sensitivity of the enzyme was markedly
      decreased above 30 degrees C, suggesting that the F1-moiety is released from the
      enzyme complex at high temperatures. This characteristic is compatible with the
      psychrophilic nature of Vibrio ABE-1.

PMID- 8987553
TI  - Acid xylanase from yeast Cryptococcus sp. S-2: purification, characterization,
      cloning, and sequencing.
AB  - A xylan-degrading enzyme produced by yeast Cryptococcus sp. S-2 was isolated and
      purified, and characterized as an endoxylanase (1,4-beta-D-xylan xylanohydrolase
      [EC 3.2.1.8]). We estimated the molecular weight and isoelectric point of
      purified xylanase (xyn-CS2) to be 22,000 and 7.4, respectively. This low
      molecular-weight xylanase had an unusual pH optimum of 2.0, and showed 75% of
      maximal activity even at pH 1.0. An open reading frame of the cDNA specified 209
      amino acids, including a putative signal peptide of 25 amino acids. The deduced
      amino acid sequence of xyn-CS2 shared significant similarities with the family-G
      xylanases of B. pumilus, C. acetobutylicum, T. reesei, and A. kawachii. Xyn-CS2
      included two unique cysteine residues in a putative catalytic region, raising the
      possibility that these residues are at least partially responsible for its
      acidophilic nature.

PMID- 8987554
TI  - A novel differentiation factor for PC12 cells from culture supernatant of mouse
      hepatocyte cell line MLE-15A2.
AB  - We have found a factor that induces neurite outgrowth of rat PC12 cells in the
      culture supernatant of the cell line MLE-15A2. This factor was designated as
      MDDF. The factor was sensitive to protease, dithiothreitol, and high-temperature
      treatments. The apparent molecular mass was 80 kDa on Superdex 200 gel
      filtration. No significant tyrosine phosphorylation was detected after MDDF
      stimulation in Western blotting analysis with anti-phosphotyrosine antibody,
      suggesting that the signal transduction may not be mediated by a tyrosine kinase
      cascade that is involved in signaling of most of the known factors. Activation of
      MAP kinase was very weak and was seen only 5 min after stimulation, suggesting
      that prolonged activation of MAP kinase was not required for neurite outgrowth
      induced by MDDF. Because the biochemical characteristics of MDDF are different
      from those of any known peptide factors that induce neurite outgrowth of PC12
      cells, MDDF may be a novel differentiation factor for PC12 cells.

PMID- 8987555
TI  - Expression of two cDNAs encoding class I chitinases of rice in Escherichia coli.
AB  - Two cDNAs encoding class I chitinases of rice were expressed in Escherichia coli.
      The cDNAs were fused to the MS2-polymerase gene in an expression vector, pEx31.
      The fusion proteins, expressed under the control of the lambda PL-promoter,
      showed the chitinase activity independent of the existence of the hevein domain.
      The enzymatic hydrolysis of colloidal chitin by the fusion proteins showed that
      the proteins were endo-type enzymes.

PMID- 8987556
TI  - Angiotensin I-converting enzyme inhibitors in autolysates of squid liver and
      mantle muscle.
AB  - Autolysis of squid liver and mantle muscle homogenates, and blends of both, each
      yielded inhibitory activity toward the angiotensin I-converting enzyme. The
      inhibitory activity and the amount of solubilized protein in each of these
      autolysates were examined over a period of 24 h. Inhibitory peptides were
      isolated from the mixed autolysate, their structures (IC50) being Tyr-Ala-Leu-Pro
      His-Ala (9.8 microM) and Gly-Tyr-Ala-Leu-Pro-His-Ala (27.3 microM).

PMID- 8987558
TI  - Cytotoxicity and suppression of immunoglobulin production against human Namalwa
      cells caused by oxidized cholesterol.
AB  - The effects of oxidized cholesterols on proliferation and IgM production of human
      lymphoblastoid Namalwa cells were examined. An oxidized cholesterol mixture, in
      contrast to cholesterol, was a potent cytotoxin to Namalwa cells. Among oxidized
      cholesterols examined, 25-hydroxycholesterol was the most cytotoxic. However, no
      oxidized cholesterol examined suppressed IgM production, although cholestanetriol
      and 7-ketocholesterol did suppress it. Thus, oxidized cholesterols are cytotoxic
      to lymphocytes, while the influence on the immunoglobulin production may be
      marginal.

PMID- 8987557
TI  - Photocytotoxicity of water-soluble fullerene derivatives.
AB  - New water-soluble fullerene carboxylic acids (1 and 2) derived from C60 and C70
      fullerenes, respectively, were examined for photocytotoxicity toward Raji cells
      (B lymphocyte). These compounds did not show any photocytotoxic effect even at 50
      microM, while pheophorbide a showed significant photocytotoxicity at 0.5 microM.
      Therefore, fullerene derivatives derived from C60 and C70 would not be practical
      agents for photodynamic therapy.

PMID- 8987559
TI  - Partial interfacial activation of Proteus vulgaris lipase overexpressed in
      Escherichia coli.
AB  - An expression plasmid carrying an alkaline lipase gene from Proteus vulgaris was
      constructed. The lipase content in Escherichia coli cells harboring the
      expression plasmid reached about 22% of total soluble protein. The purified
      enzyme displayed a partial interfacial activation toward p-nitrophenyl butyrate
      (PNPB).

PMID- 8987560
TI  - Amino acid sequence and some properties of lectin-D from the roots of pokeweed
      (Phytolacca americana).
AB  - Two pokeweed lectins, designated PL-D1 and PL-D2, have been isolated from the
      roots of pokeweed (Phytolacca americana) using chitin affinity column
      chromatography followed by gel filtration on a Sephacryl S-200 column and fast
      protein liquid chromatography on a Mono-Q column, and their amino acid sequences
      have been analyzed. PL-D1 consists of 84 amino acid residues and has a molecular
      mass of 9317, while PL-D2 has an identical sequence with PL-D1 except lack of the
      C-terminal Leu-Thr. PL-D is composed of two chitin-binding domains, A and B, with
      50% homology with each other. Both PL-Ds did not agglutinate native rabbit
      erythrocytes, but showed about 0.1% of the agglutinating activity of wheat germ
      agglutinin toward trypsin-treated erythrocytes. In the presence of beta (1-->4)
      linked oligomers of N-acetyl-D-glucosamine, which inhibit the hemagglutination,
      PL-D1 had an ultraviolet-difference spectrum with maxima at 292-294 nm and 284
      285 nm, attributed to the red shift of the tryptophan residue, suggesting the
      location of tryptophan residue(s) at or near saccharide-binding site of PL-D1.

PMID- 8987561
TI  - Inhibitory potency of Erythrina variegata proteinase inhibitors toward serine
      proteinases in the blood coagulation and fibrinolytic systems.
AB  - The Erythrina variegata Kunitz family trypsin inhibitors, ETIa and ETIb,
      prolonged the activated partial thromboplastin time (APTT) and also the
      prothrombin time (PT) of human plasma, but the Kunitz family chymotrypsin
      inhibitor, ECI, and Bowman-Birk family inhibitor, EBI, from E. variegata hardly
      prolonged these times. Trypsin inhibitors ETIa and ETIb inhibited the amidolytic
      activity of factor Xa, and ETIb but not ETIA inhibited plasma kallikrein. Neither
      ETIa nor ETIb exhibited any inhibitory activity toward beta-factor XIIa and
      thrombin. Furthermore, trypsin inhibitors ETIa and ETIb inhibited plasmin, a
      serine proteinase in the fibrinolytic system, whereas ECI and EBI did not. These
      results indicate that Erythrina Kunitz proteinase inhibitors possess different
      potency toward serine proteinases in the blood coagulation and fibrinolytic
      systems, in spite of their high similarity in amino acid sequence.

PMID- 8987562
TI  - A novel proteinaceous Kex 2 proteinase inhibitor, kexstatin, from Streptomyces
      platensis Q268.
AB  - We found a novel proteinaceous Kex 2 proteinase inhibitor, named kexstatin, in
      the culture supernatant of Streptomyces platensis Q268. The purified kexstatin
      was homogeneous by SDS-PAGE and the molecular weight was estimated to be 13,000.
      The N-terminal amino acid sequence of kexstatin has high similarity to
      Streptomyces subtilisin inhibitor (SSI), suggesting that kexstatin belongs to the
      SSI family. Kexstatin was a strong inhibitor of Kex 2 proteinase and subtilisin
      but not thermolysin, trypsin, or chymotrypsin. The IC50 value of kexstatin
      against 1 microgram of Kex 2 proteinase was 1.4 micrograms.

PMID- 8987563
TI  - The SIGNAL experiment in BIORACK: Escherichia coli in microgravity.
AB  - Microgravity affects certain physical properties of fluids, such as convection
      movement and surface tension. As a consequence, cells and living organisms may
      exhibit different behaviour in space, which may result from differences in the
      immediate environment of the cell or changes in the structure of the membrane in
      microgravity. Two experiments to examine the effects of microgravity on cell
      microenvironment and signal transduction through membranes were performed using a
      well-characterized system with different strains of the non-pathogenic Gram
      negative bacterium Escherichia coli. Our results indicate that (i) microgravity
      appears to reduce the lag period of a non-motile culture of E. coli, and (ii) the
      ompC gene, regulated by the two-component system EnvZ-OmpR, is induced as well or
      better in microgravity than in ground controls.

PMID- 8987564
TI  - DNA repair in microgravity: studies on bacteria and mammalian cells in the
      experiments REPAIR and KINETICS.
AB  - The impact of microgravity on cellular repair processes was tested in the space
      experiments REPAIR and KINETICS, which were performed during the IML-2 mission in
      the Biorack of ESA: (a) survival of spores of Bacillus subtilis HA101 after UV
      irradiation (up to 340 J m-2) in the experiment REPAIR; (b) in the experiment
      KINETICS the kinetics of DNA repair in three different test systems: rejoining of
      X-ray-induced DNA strand breaks (B1) in cells of Escherichia coli B/r (120 Gy)
      and (B2) in human fibroblasts (5 and 10 Gy) as well as (B3) induction of the SOS
      response after gamma-irradiation (300 Gy) of cells of Escherichia coli PQ37.
      Cells were irradiated prior to the space mission and were kept in a non-metabolic
      state (metabolically inactive spores of B. subtilis on membrane filters, frozen
      cells of E. coli and human fibroblasts) until incubation in orbit. Germination
      and growth of B. subtilis were initiated by humidification, E. coli and
      fibroblasts were thawed up and incubated at 37 degrees C for defined repair
      periods (up to 4.5 h), thereafter they were frozen again for laboratory analysis.
      Relevant controls were performed in-flight (1 x g reference centrifuge) and on
      ground (1 x g and 1.4 x g) The results show no significant differences between
      the microgravity samples and the corresponding controls neither in the survival
      curves nor in the kinetics of DNA strand break rejoining and induction of the SOS
      response (proven by Student's t-test, 2 P = 0.05). These observations provide
      evidence that in the microgravity environment cells are able to repair radiation
      induced DNA damage close to normality. The results suggest that a disturbance of
      cellular repair processes in the microgravity environment might not be the
      explanation for the reported synergism of radiation and microgravity.

PMID- 8987565
TI  - Cultivation of Saccharomyces cerevisiae in a bioreactor in microgravity.
AB  - Yeast cells were cultured for 8 d in a newly developed bioreactor during the
      Spacelab IML-2 mission. Two bioreactors, one stirred and one without stirring,
      were installed in the Biorack facility in space. Two control units were installed
      in the Biorack module at the Kennedy Space Center. Samples were drawn on mission
      day 3, 5, 6, 7 and 8 and preserved either by freezing or chemically fixed for
      post-flight analysis. The values of pH, pH regulation, temperature and redox
      potential were transmitted on-line to the ground station throughout the mission.
      The performance of the bioreactor was satisfactory except for a partial failure
      of the medium micropump. Despite the failure of the pump, the data support the
      following conclusions: There is a significant difference in the distribution of
      the bud scars between cells cultured at 0 x g and at 1 x g. The percentage of
      randomly distributed bud scars was significantly higher in the flight (17%) than
      in the ground control cells (5%). No remarkable differences were noted in the
      cell cycle, ultrastructure, cell proliferation, cell volume, ethanol production
      and glucose consumption.

PMID- 8987566
TI  - Effects of the space environment on Drosophila melanogaster development.
      Implications of the IML-2 experiment.
AB  - One hundred and sixty Drosophila females laid several thousands of embryos during
      the 14.5 days of the IML-2 spaceflight. The progeny were either recovered frozen
      (embryos at final stages of development and larvae), or maintained alive
      developing further until adulthood. All embryos, larvae, pupae and imagoes
      recovered were normal in morphology and function. Results from earlier
      experiments were reproduced in IML-2 with a better experimental design. We
      confirm that in Space there is a stimulation of oogenesis and that development is
      slightly delayed when compared to that of synchronous parallel ground controls.
      Nevertheless, it is clear from the accompanying 1 x g flight control centrifuge
      and from the 1.4 x g ground centrifuge samples, that centrifugation itself can
      produce similar effects, emphasizing the importance of reevaluating the role of
      the 1 x g on-flight controls. The results emphasize the apparent paradox that
      simple cellular model systems in microgravity show alterations in many
      fundamental processes such as those involved in cell signalling, while
      development, relying heavily on these key cellular mechanisms can proceed quite
      normally in the absence of gravity. The effects on development are small and more
      the consequence of a reaction to the abnormal Space environment in general than a
      specific effect of microgravity.

PMID- 8987567
TI  - Microgravity effects on Drosophila melanogaster behavior and aging. Implications
      of the IML-2 experiment.
AB  - Earlier Space experiments had indicated that young male Drosophila flies exposed
      to microgravity showed an acceleration in aging. In a 14.5-day Space Shuttle
      Flight we sent 300 young male flies with the purpose of confirming these findings
      and to establish whether changes in the behavior of the flies were responsible
      for the effect in accordance with the proposal that alterations in mitochondrial
      metabolism may be involved in the aging response. By repeatedly video-recording,
      we have found a very marked increase in the locomotor activity of the fruitflies
      in Space. The males showed an accelerated aging response upon recovery, both in
      terms of physiological vitality assays (mating and negative geotaxis) and of life
      span curves. The involvement of mitochondrial metabolism is also suggested by the
      finding of a greater decrease in mitochondrial 16S ribosomal RNA in the
      microgravity exposed flies than in ground controls. On the other hand, a parallel
      1 x g centrifuge control did not show such differences in the life-span curves
      when compared to flies exposed to a similar centrifugation on the ground.
      Drosophila females also increased their locomotor activity but did not show
      differential changes in the life-span curves. These results are discussed in
      terms of the current mechanisms of aging in multicellular eukaryotic organisms.

PMID- 8987568
TI  - Activation signals of T lymphocytes in microgravity.
AB  - Human peripheral blood lymphocytes and monocytes were activated with concanavalin
      A with or without exogenous recombinant interleukin 1 (IL-1) alone or IL-1 +
      interleukin 2 (IL-2) under microgravity conditions to test the hypothesis that
      lack of production of IL-1 by monocytes is the cause of the near total loss of
      activation observed earlier on several Spacelab flights. The 60 min failure of
      the on-board 1 x g reference centrifuge at the time of the addition of the
      activator renders the in-flight data at 1 x g unreliable. However, the data from
      a previous experiment on SLS-1 show that there is no difference between the
      results from the in-flight 1 x g centrifuge and 1 x g on ground. The comparison
      between the data of the cultures at 0 x g in space and of the synchronous control
      at 1 x g on ground show that exogenous IL-1 and IL-2 do not prevent the loss of
      activity (measured as the mitotic index) at 0 x g; production of interferon
      gamma, however, is partially restored. In contrast to a previous experiment in
      space, the production of IL-1 is not inhibited.

PMID- 8987569
TI  - Movements and interactions of leukocytes in microgravity.
AB  - The mitogenic activation of human lymphocytes resuspended in vitro is
      dramatically reduced in microgravity. As cell-cell contacts are one of the
      elements essential for activation, the behaviour of human leukocytes (mainly
      lymphocytes and monocytes as accessory cells) in the presence of the mitogen
      concanavalin A was studied in the centrifuge microscope NIZEMI at 0 x g.
      Aggregates (formed by intercellular bindings of membrane glycoproteins via the
      tetravalent alpha-glucoside ligand concanavalin A) were found at 0 x g as well as
      at 1 x g already 12 h after the addition of the mitogen. In general, the
      aggregates observed at 0 x g after an incubation time of 46 and 78 h were smaller
      than the corresponding aggregates in the ground control. The findings are of
      primary importance since they confirm the indirect evidence we had from earlier
      Spacelab experiments and demonstrate that cell-cell contacts are occurring also
      in microgravity. In addition, single cells in 0 x g show a significant higher
      locomotion velocity than the cells at 1 x g. The fact that the locomotion
      capability is not decreased during the 78-h incubation with concanavalin A
      provides further evidence that the cells are not proceeding through the cell
      cycle.

PMID- 8987570
TI  - Feeding frequency affects cultured rat pituitary cells in low gravity.
AB  - In this report, we describe the results of a rat pituitary cell culture
      experiment done on STS-65 in which the effect of cell feeding on the release of
      the six anterior pituitary hormones was studied. We found complex microgravity
      related interactions between the frequency of cell feeding and the quantity and
      quality (i.e. biological activity) of some of the six hormones released in
      flight. Analyses of growth hormone (GH) released from cells into culture media on
      different mission days using gel filtration and ion exchange chromatography
      yielded qualitatively similar results between ground and flight samples. Lack of
      cell feeding resulted in extensive cell clumping in flight (but not ground)
      cultures. Vigorous fibroblast growth occurred in both ground and flight cultures
      fed 4 times. These results are interpreted within the context of autocrine and/or
      paracrine feedback interactions. Finally, the payload specialist successfully
      prepared a fresh trypsin solution in microgravity, detached the cells from their
      surface and reinserted them back into the culture chamber. These cells reattached
      and continued to release hormone in microgravity. In summary, this experiment
      shows that pituitary cells are microgravity sensitive and that coupled operations
      routinely associated with laboratory cell culture can also be accomplished in low
      gravity.

PMID- 8987572
TI  - An improved quantitative RT-PCR fluorescent method for analysis of gene
      transcripts in the STS-65 space shuttle experiment.
AB  - We describe a reverse transcription polymerase chain reaction (RT-PCR) technique
      using fluorescent dUTP to examine changes in mRNA level in samples. In this
      procedure, the amplified product is identified by the fluorescent detection
      system in an automated DNA sequencer, and if the MW of the DNA/RNA or the
      fluorescent dye is different, several samples can be analyzed in a single lane.
      The basis for this technique is similar to that of radiolabeled methods, and we
      applied this technique for the comparison of the expression level of the rat c
      myc gene in osteoblasts exposed to microgravity and unit gravity conditions.
      Using the fluorescent- and radiolabeled methods, the level of rat c-myc mRNA were
      compared quantitatively and the results demonstrated that the c-myc expression
      level was not altered by microgravity. Therefore, this fluorescent RT-PCR
      technique is useful for gene expression analysis particularly when the samples
      are limited, such as in space flight experiments. The method also allows for
      rapid assessment of mRNA changes in many samples simultaneously.

PMID- 8987571
TI  - Microgravity induces prostaglandin E2 and interleukin-6 production in normal rat
      osteoblasts: role in bone demineralization.
AB  - It has been suggested that microgravity alters bone metabolism. Evidence for this
      phenomenon includes the negative calcium balance and decreased bone density in
      astronauts, as well as, inhibition of bone formation in rats flown for 2 to 3
      weeks. However, the specific mechanisms that modulate these changes in
      microgravity are unknown. The purpose of this study was to clarify the mechanism
      of microgravity-induced bone demineralization using normal rat osteoblasts
      obtained from femur marrow cultures. The osteoblasts were cultured for 5 days
      during a Shuttle-Spacelab flight (STS-65). After collection of the culture
      medium, the cellular DNA and RNA were fixed on board. Enzyme-immunoassay of the
      culture medium for prostaglandin E2 (PGE2) indicated that microgravity induced a
      4.5- to 136-fold increase in flight samples as compared to the ground control
      cultures. This increase of PGE2 production was consistent with a 3.3- to 9.5-fold
      elevation of inducible prostaglandin G/H synthase-2 (PGHS-2) mRNA, quantitated by
      reverse transcription-polymerase chain reaction (RT-PCR). The mRNA induction for
      the constitutive isozyme PGHS-1 was less than that for PGHS-2. The interleukin-6
      (IL-6) mRNA was also increased (6.4- to 9.3-fold) in microgravity as compared to
      the ground controls. Since PGE2 and IL-6 are both known to play a role in
      osteoclast formation and bone resorption, these data provide molecular mechanisms
      that contribute to our understanding of microgravity-induced alterations in the
      bone resorption process.

PMID- 8987575
TI  - Bioprocessing in microgravity: free flow electrophoresis of C. elegans DNA.
AB  - Free flow electrophoresis of a nematode C. elegans DNA was carried out on the
      space shuttle flight STS65/Colombia. During the processes of the experiment, the
      house keeping data of the FFEU and the electrophoretic migration profiles were
      monitored at POCC (Payload Operations Control Center) of MSFC (Marshall Space
      Flight Center, Alabama) according to the real-time down-link system. The three
      dimensional electropherogram (3DEP) on the basis of the down-linked data showed
      some trouble with the apparatus but three sequential experiments indicated this
      disturbance of the apparatus is rather preferably stable. Comparing post-flight
      analyses of the DNA component fractionated, that is, amplification by PCR method,
      it revealed that the DNAs were separated approximately into two peaks: one of
      them contained seven-fold higher content of DNA estimated by a sod-4 gene probe
      than an unc-6 gene probe. These results suggested that this separation technique
      could be still more effective for the separation of biological macromolecules
      such as DNA, and the efficiency of separation of the free flow electrophoresis
      under microgravity environment was useful.

PMID- 8987574
TI  - Bioprocessing in microgravity: applications of continuous flow electrophoresis to
      rat anterior pituitary particles.
AB  - In this report we describe the results of a continuous flow electrophoresis (CFE)
      experiment done on STS-65 in which we tested the idea that intracellular growth
      hormone (GH) particles contained in a cell lysate prepared from cultured rat
      anterior pituitary cells in microgravity might have different electrophoretic
      mobilities from those in a synchronous ground control cell lysate. Collectively,
      the results suggested that CFE processing in microgravity was better than on
      earth; more sample could be processed/time (6 x) and more variant forms of GH
      molecules could be resolved as well. We had also hoped to carry out a pituitary
      cell CFE experiment, but failure of the hardware required that the actual cell
      electrophoresis trials be done on earth shortly after Shuttle landing. Data from
      these experiments showed that space-flown cells possessed a higher
      electrophoretic mobility than ground control cells, thereby offering evidence for
      the idea that exposure of cultured cells to microgravity can change their net
      surface charge-density especially when the cells are fed. Collectively, the
      results from this pituitary cell experiment document the advantage of using
      coupled cell culture and CFE techniques in the microgravity environment.

PMID- 8987576
TI  - Preservation of viable biological samples for experiments in space laboratories.
AB  - Standard viable preservation methods for biological samples using low
      temperatures have been investigated concerning their storage capabilities under
      higher temperature levels than usual. For a representative set of organism
      classes (plants, mammalian cells, arthropods and aquatic invertebrates), the
      minimum appropriate storage conditions have been identified by screening storage
      temperatures at -196 degrees, -80 degrees, -20 degrees, +4 degrees, +20
      degrees/25 degrees C for periods from 2 days to 4 weeks. For storage below 0
      degree C, as a typical cryopreservative, dimethylsulfoxide (DMSO) was used. For
      some samples, the addition of trehalose (as cryopreservative) and the use of a
      nitrogen atmosphere were investigated. After storage, the material was tested for
      vitality. The findings demonstrated that acceptable preservation can be achieved
      under higher storage temperatures than are typically applied. Small, dense
      cultured plant cells survive for 21 d when moderately cooled (+4 degrees to -20
      degrees C); addition of trehalose enhances viability at -20 degrees C. For
      mammalian cells, the results show that human lymphocytes can be preserved for 3 d
      at 25 degrees C, 7 d at 4 degrees C and 28 d at -80 degrees C. Friend leukaemia
      virus transformed cells can be stored for 3 d at 25 degrees C, 14 d at 4 degrees
      C and 28 d at -80 degrees C. Hybridoma cells can be kept 7 d at 4 degrees C and
      28 d at -20 degrees C or -80 degrees C. Model arthropod systems are well
      preserved for 2 weeks if maintained at lower temperatures that vary depending on
      the species and/or stage of development; e.g., 12 degrees C for Drosophila
      imagoes and 4-6 degrees C for Artemia nauplii. For aquatic invertebrates such as
      sea urchins, embryonic and larval stages can be preserved for several weeks at +6
      degrees C, whereas sperm and eggs can best be stored at + 4 degrees C for up to 5
      d at maximum. These results enhance the range of feasible space experiments with
      biological systems. Moreover, for typical terrestrial preservation methods,
      considerable modification potential is identified.

PMID- 8987579
TI  - Chemistry of biologically active benzoxazinoids.
AB  - 2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) and its desmethoxy
      derivative (DIBOA) are major allelochemicals produced by corn, wheat, rye and
      related monocotyledons. These benzoxazinone derivatives have a wide variety of
      biological actions, including antifungal and mutagenic activities. Structure
      activity relationships of these compounds and their derivatives (benzoxazinoids),
      the reactivity of benzoxazinoids with nucleophiles, and the substituent effects
      of the 7-methoxy and 2-hydroxy groups are discussed in relation to the molecular
      mechanisms of the biological activities.

PMID- 8987577
TI  - Transgenic insect cells: mosquito cell mutants and the dihydrofolate reductase
      gene.

PMID- 8987580
TI  - Dhurrin-6'-glucoside, a cyanogenic diglucoside from Sorghum bicolor.
AB  - A novel cyanogenic diglucoside has been isolated from methanolic extracts of
      young seedlings of Sorghum bicolor. Its structure was established as dhurrin-6
      glucoside from NMR, mass spectrometry and enzymatic hydrolysis data. Compared
      with dhurrin, which is the major cyanogenic glucoside in sorghum leaves, dhurrin
      6-glucoside occurs only in low concentrations. In contrast, however, the
      diglucoside is present in significant amounts in guttation droplets of young
      Sorghum seedlings. The presence of the diglucoside and its occurrence in
      apoplasmic exudates supports the hypothesis that diglucosides represent
      metabolites of cyanogenic monoglucosides which can be translocated within the
      plant.

PMID- 8987581
TI  - Essential oils from fruits of three types of Thapsia villosa.
AB  - Thapsia villosa has been divided into five types and previous analyses of the
      essential oils from the fruits of two of these types showed that limonene and
      methyl eugenol were the major constituents. The composition of the essential oils
      from the fruits of the other three types of T. villosa, with the chromosome
      numbers 2n = 22 (2x), 2n = 22 (2x) and 2n = 44 (4x), is reported here. The oil
      from all three types shows a similar chemical profile, with geranyl acetate as
      the main constituent accounting for 78-92% of the total oil. The composition of
      the essential oils from these plants is clearly different from the first two
      types of T. villosa mentioned, and also from the other species within the genus
      Thapsia.

PMID- 8987582
TI  - Mono- and diglycosides of (E)-6,9-dihydroxymegastigma-4,7-dien-3-one in Vitis
      vinifera wine.
AB  - Two beta-D-glucopyranosides and two 6-O-beta-D-apiofuranosyl-beta-D
      glucopyranosides of (E)-6,9-dihydroxymegastigma-4,7-dien-3-one were isolated from
      Vitis vinifera cv. Gewurztraminer wine and their structures were established by
      NMR spectroscopy.

PMID- 8987578
TI  - Baculovirus--insect cell interactions.
AB  - Baculovirus interactions with host cells range from the physical interactions
      that occur during viral binding and entry, to the complex and subtle mechanisms
      that regulate host gene expression and modify and regulate cellular and
      organismal physiology and defenses. Fundamental studies of baculovirus
      biochemistry and molecular biology have yielded many interesting and important
      discoveries on the mechanisms of these virus-host interactions. Information from
      such studies has also resulted in exciting new strategies for environmentally
      sound insect pest control, and in the development and improvement of a valuable
      eukaryotic expression vector system. In addition a number of important and
      valuable model biological systems have emerged from studies of baculoviruses.
      These include robust systems for studies of eukaryotic transcription, viral DNA
      replication, membrane fusion, and apoptosis. Because functions have been
      identified for only a small number of baculovirus genes, we can expect many
      exciting new discoveries in the future and an unfolding of the complex and
      intricate relationship between baculoviruses and insect cells.

PMID- 8987583
TI  - Aferoside A, a steroidal saponin from Costus afer.
AB  - A new steroidal saponin, aferoside A, has been isolated from the roots of Costus
      afer. Its structure was established as 3-O-([beta-D-apiofuranosyl-(1-->2)]-[alpha
      L-rhamnopyranosyl-(1--> 4)]-beta-D-glucopyranosyl)-25(R)-spirost-5-en-3 beta-ol
      by chemical transformations and various spectroscopic methods, mainly 2D NMR
      techniques (COSY, HMQC and HMBC).

PMID- 8987584
TI  - Nitrile hydratase and its application to industrial production of acrylamide.
AB  - Nitrile hydratase (NHase) was discovered in our laboratory. This enzyme was
      purified and characterized from various microorganisms. NHases are roughly
      classified into two groups according to the metal involved: Fe-type and Co-type.
      NHases are expected to have great potential as catalysts in organic chemical
      processing because they can convert nitriles to the corresponding higher-value
      amides under mild conditions. We have used microbial enzymes for the production
      of useful compounds: NHase has been used for the industrial production
      (production capacity: 30,000 tons/year) of acrylamide from acrylonitrile. This is
      the first successful example of a biotransformation process for the manufacture
      of a commodity chemical. This review summarizes the history of NHase studied not
      only from a basic standpoint but also from an applied point of view.

PMID- 8987585
TI  - Cloning and nucleotide sequence of ApaLI restriction-modification system from
      Acetobacter pasteurianus IFO 13753.
AB  - The ApaLI restriction-modification system from Acetobacter pasteurianus IFO 13753
      recognizes the nucleotide sequence GTGCAC. The gene coding for the ApaLI
      methylase (M.ApaLI) was cloned into Escherichia coli DH5 alpha MCR, and the
      nucleotide sequence of the gene was analyzed. The M.ApaLI gene coded for a
      protein of 429 amino acid residues (molecular mass, 46,554 daltons). The ApaLI
      restriction endonuclease (R.ApaLI) gene was analyzed by inverse polymerase chain
      reaction. The R.ApaLI gene coded for a protein of 375 amino acid residues
      (molecular mass, 42,143 daltons). The two genes had the same orientation
      separated by two base pairs. The deduced amino acid sequence of M.ApaLI shows
      significant similarities to the family of cytosine-5 methylases. However, the
      deduced amino acid sequence of R.ApaLI did not have as much relatedness in the
      nucleotide sequence, when compared with those of the other restriction
      endonucleases already reported.

PMID- 8987586
TI  - Hydrolysis kinetics of okara and characterization of its water-soluble
      polysaccharides.
AB  - As a part of a study of reuse of waste okara, the kinetic mechanism of okara
      hydrolysis and the properties of the water-soluble polysaccharides (WSP)
      extracted were investigated. Okara was hydrolyzed by being autoclaved at pH 4.5
      in two volume of water with or without a chelator such as hexametaphosphate.
      Okara hydrolysis proceeded by surface degradation mechanism without a chelator.
      Characterization of WSP suggested that the "egg-box regions" in okara were
      susceptible to degradation by a chelator and that the "non-egg-box regions"
      contained WSP linked with hydrophobic proteins. WSP with a molecular weight of
      more than 10(5) and the amount of protein bound to the polysaccharides seemed to
      govern their emulsifying characteristics.

PMID- 8987587
TI  - Accumulation of benzoic acid in suspension cultured cells of Pinus thunbergii
      Parl. in response to phenylacetic acid administration.
AB  - The generation and accumulation of both benzoic acid (BA) and its conjugates were
      induced in suspension cultured cells of Pinus thunbergii by administering either
      phenylacetic acid (PA), a toxic metabolite of Bacillus cereus (strain HY-3)
      accompanying the pine wood nematode, or a lyophilized culture supernatant of this
      bacterium. BA conjugates reached their maximal levels in quantity two days after
      the administration and then decreased gradually until the 14th day, while BA
      increased significantly throughout this period. This pattern is similar to that
      in 3-year-old pine trees treated with PA, suggesting that the pathological
      reaction of pine tissues to the PA toxin might be involved in the pathogenesis
      mechanism for the pine wilt disease.

PMID- 8987588
TI  - Relationship between the pathogenicity of the pine wood nematode, Bursaphelenchus
      xylophilus, and phenylacetic acid production.
AB  - Phenylacetic acid (PA), a toxin produced by three strains of bacteria
      accompanying the pine wood nematode, Bursaphelenchus xylophilus, was found to be
      formed in a culture of the nematode. An animal nutrient, nutrient broth (NB)
      medium, was more suitable for PA production of the accompanying bacteria than a
      vegetable nutrient, potato sucrose malt extract (PSM) medium. It is presumed that
      dead nematodes in the PSM medium provided the bacteria with nutrient for PA
      production. In the culture of virulent isolate OKD-3, more PA was detected than
      in that of less-virulent isolate OKD-1. PA production of the accompanying
      bacteria can dominate the pathogenicity of the nematode.

PMID- 8987589
TI  - Effect of dietary L-glutamine on the hepatotoxic action of D-galactosamine in
      rats.
AB  - The protective effect of dietary L-glutamine against the hepatotoxic action of D
      galactosamine (GaIN) was investigated by model experiments with rats. Rats fed
      with 20% casein diets containing 10% free amino acids were injected with GaIN,
      and the serum aspartate aminotransferase, alanine aminotransferase and lactate
      dehydrogenase activities and the hepatic glycogen content were assayed 20 hours
      after the injection. These enzyme activities in the group fed with 10% L
      glutamine diet for 8 days were lower than those in the groups fed with the
      control, 10% L-glutamic acid and 10% L-alanine diets for 8 days. The more
      prolonged the feeding period with the 10% L-glutamine diet was, the more the
      serum activity levels of such enzymes were decreased. Although neomycin also
      lowered these enzyme activities, its simultaneous ingestion with neomycin did not
      show any additive or synergistic effect. The hepatic glycogen content in the 10%
      glutamine group still remained high after the GaIN treatment. It is therefore
      assumed that the effectiveness of glutamine intake would have been mediated by
      glycogen metabolism rather than by uridine metabolism.

PMID- 8987590
TI  - A new screening method for the selection of Lactobacillus acidophilus group
      lactic acid bacteria with high adhesion to human colonic mucosa.
AB  - A hemagglutination (HA) assay was done for the screening of lectin-like
      components in surface layer protein (SLP) from Lactobacillus (L.) acidophilus A
      group strains. The new screening method, using polystyrene beads coated with rat
      colonic mucin (RCM), which combines sugar chains similar to those of human
      colonic mucin, was also done. The results showed that the HA assay was not a good
      indicator for selecting strains having high adhesion to the human intestinal
      tract. The SLPs from 3 strains that strongly bound to RCM also bound well to
      carbohydrate portions of Carnoy's-fixed human colonic mucous layer. These results
      suggest that this method is a new promising screening technique for the L.
      acidophilus strains having high adhesion to the human intestinal tract.

PMID- 8987591
TI  - S-methyl methanethiosulfonate, bio-antimutagen in homogenates of Cruciferae and
      Liliaceae vegetables.
AB  - The isolation of a new type of bio-antimutagen, S-methyl methanethiosulfonate
      (MMTS), from cauliflower (Brassica oleracea var. botrytis) and the distribution
      and formation of MMTS in Cruciferae and Liliaceae vegetables are described. For
      the separation and purification, cauliflower curds were homogenized, extracted
      with acetone, and then purified by organic solvent extraction and by various
      processes of chromatographic separation. The chemical structure of an active
      principle was identified as MMTS by GC-MS and 1H-NMR analyses. MMTS was widely
      found in vegetable homogenates of the Cruciferae and Liliaceae species, and is
      found from its precursor S-methyl-L-cysteinesulfoxide (SMCS), by wounding the
      vegetable tissues. Wounding may induce C-S lyase, which converts SMCS to MMTS.
      The amount of MMTS formed was affected by the pH value for C- lyase, but not by
      the SMCS content in a tissue homogenate.

PMID- 8987593
TI  - Effects of tea (Camellia sinensis) chemical compounds on ethanol metabolism in
      ICR mice.
AB  - The effects of a green tea (Camellia sinensis) extract on ethanol metabolism in
      ICR male mice were studied. A crude green tea extract (GTE) and the tea
      components as (-)-epigallocatechin gallate (EGCg), (-)-epigallocatechin (EGC),
      and caffeine were administered before the tests. One hour later, the mice were
      orally given 2g/kg body weight (b.w.) of ethanol (20% ethanol w/v). The results
      show that the levels in the blood and liver of ethanol and acetaldehyde were
      lower, and that the levels of acetate and acetone were higher than in the
      controls orally given 500 mg/kg b.w. of GTE. After the administration of 75 mg/kg
      b.w. and 225 mg/kg b.w. of EGCg, the acetate and acetone concentrations in the
      blood and liver were lower than in the controls. The mice given caffeine at the
      same dose as that in GTE showed almost the same effects as the group treated with
      GTE. This suggests that EGCg and caffeine, the principal components of GTE, both
      had an effect on ethanol metabolism.

PMID- 8987594
TI  - Increased conversion ratio of tryptophan to niacin by the administration of
      clofibrate, a hypolipidemic drug, to rats.
AB  - The effect of clofibrate, a hypolipidemic drug and also known as a peroxisomal
      proliferator, on the conversion ratio of tryptophan to niacin was investigated by
      using rats. The rats were fed with a nicotinic acid-free, 20% casein diet
      (control group) or the same diet + 0.25% clofibrate group) for 19 days. The
      conversion ratio gradually increased with increasing number of days. Around day
      8, the ratio was about 10-times higher in the clofibrate group than in the
      control group, and the value remained almost constant after that day. The content
      of liver total nicotinamide was higher in the clofibrate group than in the
      control group. Among the enzymes involved in the conversion of tryptophan to
      niacin, the aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) activity,
      which is critical in the conversion, was lower in the clofibrate group than in
      the control group. As the change in ACMSDase activity took several days, there is
      a possibility that clofibrate decreased the biosynthesis of ACMSDase protein
      and/or mRNA. To learn whether the increase in the conversion ratio by clofibrate
      would be nutritionally meaningful or not, the growth-promoting activity of
      clofibrate was determined by using weanling rats fed with a nicotinic acid-free,
      tryptophan-limiting diet (basal diet). As a result, the body weight gain was
      higher in the clofibrate group than in the basal group. This result shows that
      clofibrate enhanced the conversion ratio without any side-effects under the
      conditions used and supports again the claim that the activity of ACMSDase exerts
      a critical influence on the tryptophan-NAD conversion.

PMID- 8987595
TI  - Role of the intrachain disulfide bond of ovalbumin during conversion into S
      ovalbumin.
AB  - Disulfide-reduced and carboxymethylated ovalbumin was treated at pH 9.9 and 55
      degrees C for 24 h as a specific condition for preparation of S-ovalbumin. The
      stability and conformation of the product were investigated. Such alkaline
      treatment converted native protein to S-ovalbumin, but this modified ovalbumin
      was not stabilized, according to results of calorimetric analysis. Instead, it
      had lost its native like conformation; the magnitude of CD spectra decreased. The
      conformation after alkaline treatment was not clear, but the possibility of
      aggregation was excluded by electrophoretic analysis. These observations showed
      that the transformation of native ovalbumin into S-ovalbumin requires the
      presence of the disulfide bond.

PMID- 8987597
TI  - Characterization of a matrix protein in the gastroliths of the crayfish
      Procambarus clarkii.
AB  - As a first step in understanding the calcification mechanism, a matrix protein in
      the gastrolith of the crayfish Procambarus clarkii was purified and sequenced.
      The protein was insoluble in acid, but after trypsin digestion, it dissolved in 6
      M urea. The trypsin-digested protein dissolved in urea solution was purified by
      reversed-phase HPLC and designated gastrolith matrix protein fragment. The
      fragment had a molecular weight of 9658 and a blocked amino terminus. It had
      tandemly repeated units not reported before at the central part of the sequence,
      with each unit being Gly-Ser-X1-X2-Phe as the most typical sequence. This peptide
      was found associated with chitin, a main component of the organic matrix.

PMID- 8987596
TI  - Molecular cloning of cDNA that encodes chymotrypsin inhibitor ECI from Erythrina
      variegata seeds and its expression in Escherichia coli.
AB  - Synthetic oligonucleotides representing all possible sequences of the N-terminal
      and internal amino acid sequences of the chymotrypsin inhibitor ECI from
      Erythrina variegata seeds were used to generate a probe specific for ECI-related
      sequences by the polymerase chain reaction on the E. variegata genomic DNA. A
      lambda phage cDNA library constructed from poly(A+) RNA from maturing seeds was
      screened with the ECI gene thus obtained as a probe and characterized by DNA
      sequencing. The cloned ECI cDNA comprised 737 nucleotides and one open reading
      frame that encoded a polypeptide chain of 203 amino acids including a signal
      peptide composed of 24 amino acids. An expression plasmid was designed for export
      of the recombinant inhibitor into the periplasm. For this purpose, the cDNA
      fragment encoding matured ECI was ligated into the NcoI and BamHI sites following
      the pel B signal sequence in the expression vector pET-22b and expressed in
      Escherichia coli BL21 (DE3). However, this attempt failed as the recombinant
      inhibitor caused the formation of inclusion bodies in E. coli cells as a
      heterologous preprotein (SR-ECI), with the pel B upstream leader. SR-ECI was made
      soluble and renatured by refolding and reoxidation, and subsequently processed
      with pronase to give rise to recombinant ECI (R-ECI) that had an extra methionine
      residue attached to the N-terminal amino acid of ECI. Purified R-ECI inhibited
      chymotrypsin almost as strongly as authentic ECI.

PMID- 8987598
TI  - Expression of 135-kDa insecticidal protein gene from Bacillus thuringiensis in
      the yeast Saccharomyces cerevisiae.
AB  - Bacillus thuringiensis subsp. aizawai produces 130-kDa and 135-kDa (CryIA(a))
      insecticidal proteins. When Saccharomyces cerevisiae was transformed by the
      vector carrying a cryIA(a) gene, the gene expression could not be observed. When
      the 5'-upstream region from the initiation codon was removed using a synthetic
      oligonucleotide, the CryIA(a) protein was successfully synthesized in yeast. The
      yeast extract containing CryIA(a) protein had insecticidal activity against
      Plutella xylostella larvae.

PMID- 8987599
TI  - S-methylmethionine sulfonium in fruits of citrus hybrids.
AB  - The S-methylmethionine sulfonium (MMS) concentrations in fruits of citrus hybrids
      were measured, and found to increase during ripening of the fruit. However, there
      of eleven hybrids of 'Seto unshiu' crossed with 'Morita ponkan' and four of 9
      hybrids of 'Murcott' tangor crossed with 'Seto unshiu' had low MMS concentrations
      even at late harvest stage. Crossbreeding is useful in producing new citrus
      fruits that have juices with the desirable characteristics of their parents
      without formation of dimethyl sulfide which is an off-flavor.

PMID- 8987600
TI  - Effects of the glycoprotein sugar chains on the amino-carbonyl reaction of
      chicken and Japanese quail ovomucoids with glucose.
AB  - The amino-carbonyl reactions of two glycoproteins, chicken ovomucoid and quail
      ovomucoid, which have similar amino acid sequences but different sugar chains,
      were compared. The free guanidino groups, but not amino groups, of chicken
      ovomucoid decreased more rapidly than those of quail ovomucoid during reaction
      with glucose. Protein polymerization and formation or brownish or fluorescent
      compounds also occurred more quickly in the chicken ovomucoid. These results
      suggested that the sugar chain moieties affect the amino-carbonyl reaction of
      glycoproteins with deducing sugars, especially at advanced stages of the
      reaction.

PMID- 8987602
TI  - Synthesis of 7-methoxyapigeninidin and its fungicidal activity against
      Gloeocercospora sorghi.
AB  - In the structure of sakuranetin, which was isolated as a phytoalexin from the
      rice plant, the methoxy group at C-7 has been shown to be important for its high
      activity. Apigeninidin was isolated as a phytoalexin from sorghum, but it had no
      methoxy group at C-7. We prepared 7-methoxyapigeninidin and compared its
      fungicidal activity with that of apigeninidin. The 7-methoxyapigeninidin showed
      higher activity against sorghum fungi than apigeninidin, suggesting that the
      methoxy group at C-7 was important for the high fungicidal activity.

PMID- 8987601
TI  - Inhibition of Escherichia coli heat-labile enterotoxin by an amino carbonyl
      product, lactose-alpha-lactalbumin.
AB  - The inhibition by lactose-alpha-lactalbumin amino carbonyl product of Escherichia
      coli heat-labile enterotoxin was studied by GM1-ELISA and by assay with CHO-K1
      cells. The product dose-dependently inhibited the binding of the enterotoxin to
      GM1 ganglioside and decreased the morphological change of CHO-K1 cells caused by
      this toxin. The results suggest that this product may be a receptor analogue in
      the intestine.

PMID- 8987603
TI  - Binding of egg white proteins to viruses.
AB  - The binding of some egg white proteins to bovine rotavirus, hen new castle
      disease virus (NDV), and human influenza virus (IV) was investigated by using the
      hemagglutination inhibition (HI) test and supplemented by an enzyme-linked
      immunosorbent assay (ELISA). In comparison with other egg white proteins,
      ovomucin showed the highest affinity for the three viruses, while ovomucoid
      showed only slight affinity for NDV in the HI test and ELISA.

PMID- 8987604
TI  - Differences in hemagglutination inhibition activity against bovine rotavirus and
      hen Newcastle disease virus based on the subunits in hen egg white ovomucin.
AB  - The hemagglutination inhibition (HI) activity of ovomucin (OM) subunits, and the
      effects of alkylation before and after reduction and protease treatments on the
      HI activity of OM to bovine rotavirus (RV) and hen newcastle disease virus (NDV)
      were investigated. The appearance of the HI activity of Om against RV was
      accomplished by a macromolecule composed of alpha- and beta-subunits, while that
      against NDV required the beta-subunit moiety only.

PMID- 8987605
TI  - Ansamycin antibiotics as free radical scavengers isolated from Streptomyces by
      using the bactericidal action of the hydroxyl radical.
AB  - Ansamycin antibiotics (1-4) were isolated from the cultured broth of Streptomyces
      sp. USF-319 strain as a result of our screening for free radical scavengers. They
      inhibited the bactericidal effect of the Fenton reagent toward Bacillus subtilis
      by their radical scavenging activity. Some of them also showed inhibitory
      activity against lipid peroxidation and lipoxygenases.

PMID- 8987606
TI  - Purification and characterization of ferredoxin from Hydrogenobacter thermophilus
      strain TK-6.
AB  - Ferredoxin was purified from cells of Hydrogenobacter thermophilus strain TK-6.
      Purification was performed aerobically by the addition of octyl-beta-glucoside to
      the buffers. The purified ferredoxin had a molecular mass of 13,000 and contained
      a [4F3-4S] cluster. The protein had a long stretch at the N-terminal region;
      however, the sequence was not similar to the sequences of ferredoxins with a long
      stretch from Archaebacteria.

PMID- 8987607
TI  - Ice nucleus production of Fusarium moniliforme var. subglutinans in relation to
      its growth characteristics.
AB  - The effects of culture conditions on the ice nucleus production of Fusarium
      moniliforme var. subglutinans isolated from the gut of larvae of the rice stem
      borer (Chilo suppressalis Walker) were examined. The ice nucleus production was
      only affected by cultivation temperature and pH: the optimum temperature and pH
      were 15 degrees C to 20 degrees C and 4.0 to 6.0, respectively.

PMID- 8987609
TI  - Changes in vacuolar protease activities during synchronous culture of
      Saccharomyces cerevisiae.
AB  - Enzymatic activities of proteinases A and B, carboxypeptidase Y, and
      aminopeptidase I, vacuolar enzymes in beer yeast, Saccharomyces cerevisiae, were
      measured at different stages of growth in the synchronous culture. All enzymatic
      activities fluctuated synchronously during the cell growth in a periodical cycle.
      The maximum activities were observed before cytokinesis and the minimum
      activities were found just after completing cytokinesis.

PMID- 8987608
TI  - Simple detection of xylosidase activity in single colonies, using 1-naphthyl-beta
      D-xylopyranoside.
AB  - Since the xylosidase of Bacillus pumilus hydrolyzed 1-naphthyl-beta-D
      xylopyranoside (naphthyl-X) to produce xylose and 1-naphthol and a chromogenic
      azo compound is produced by coupling 1-naphthol and Fast Blue Salt B, a simple
      method for detection of xylosidase activity in single colonies was studied.
      Escherichia coli JM109 carrying the xylosidase gene of B. pumilus was cultivated
      at 37 degrees C for 18 h on a LB plate containing 0.5 mg/ml naphthyl-X, and then
      the plate was overlaid with 3 ml of a top layer containing 24 mg of agar and 6 mg
      of Fast Blue Salt B. After incubation of the plate at 37 degrees C for 1 h, each
      colony became reddish-brown. Even a small colony with xylosidase on the plate was
      easily distinguished from colonies without the enzyme.

PMID- 8987610
TI  - Cleavage specificity of coxsackievirus 3C proteinase for peptide substrate (2):
      Importance of the P2 and P4 residues.
AB  - Coxsackievirus 3C proteinase (3Cpro) cleaves between Gln and Gly, but additional
      amino acids are required to constitute a cleavage site. To investigate the
      additional sequence requirements, cleavages of the peptide substrate, and its
      derivatives were examined. Substitutions of each residue from the P2 to P5
      positions showed the importance of the P2 Phe and P4 Ala for recognition by
      3Cpro.

PMID- 8987611
TI  - Buckwheat protein extract suppression of the growth depression in rats induced by
      feeding amaranth (Food Red No. 2).
AB  - Dietary fiber has an ameliorative effect on the toxicity of amaranth (Food Red
      No. 2). To test the possibility that a buckwheat protein extract (BWPE) has
      dietary fiber-like activity by virtue of its low digestibility, we examined the
      influence of BWPE on amaranth toxicity in rats. The results show that BWPE
      containing diet suppressed the growth depression induced by the dietary addition
      of 5% amaranth.

PMID- 8987612
TI  - Protein sequences of two keto ester reductases: possible identity as hypothetical
      proteins.
AB  - We determined the amino acid sequences of two keto ester reductases (YKER-V and 
      VI) purified from a cell-free extract of Saccharomyces cerevisiae. The N-terminal
      and internal amino acid sequences of YKER-VI (AcKR) were in agreement with the
      sequence of hypothetical 36.4-kDa protein (S. cerevisiae chromosome X reading
      frame ORF YJR105w) in yeast. The N-terminal amino acid sequence of YKER-V was
      also identical with that of the hypothetical protein coded by yeast chromosome
      XIV or II. These results suggested that two hypothetical proteins were expressed
      as keto ester reductases in yeast cells.

PMID- 8987613
TI  - Comparison of thermal and guanidine hydrochloride denaturation behaviors of
      glucoamylase from the STA1 gene of Saccharomyces cerevisiae var. diastaticus.
AB  - To investigate the relationships between enzyme inactivation and conformational
      change, the effects of heat and guanidine hydrochloride (GnHC1) on the STA1 gene
      glucoamylase (STA1GA) of Saccharomyces cerevisiae var. diastaticus were examined
      by circular dichroism and fluorescence spectroscopies. A conformational change
      was observed in the thermal denaturation of STA1GA, while extensive enzyme
      inactivation occurred in GnHC1 denaturation before noticeable conformational
      change.

PMID- 8987614
TI  - Analysis of the Escherichia coli gntT and gntU genes and comparison of the
      products with their homologues.
AB  - The Escherichia coli gluconate permease genes, gntT ant gntU, were cloned and
      characterized. At least four homologues to GntT were found in E. coli by database
      searching. These proteins including GntT and GntU appear to have similar
      topological structures with 14 membrane-spanning segments, suggesting that they
      constitute a GntP family.

PMID- 8987615
TI  - Cytokinin controls the cell cycle at mitosis by stimulating the tyrosine
      dephosphorylation and activation of p34cdc2-like H1 histone kinase.
AB  - In excised pith parenchyma from Nicotiana tabacum L. cv. Wisconsin Havana 38,
      auxin (naphthalene-1-acetic acid) together with cytokinin (6-benzylaminopurine)
      induced a greater than 40-fold increase in a p34cdc2-like protein, recoverable in
      the p13suc1-binding fraction, that had high H1 histone kinase activity, but
      enzyme induced without cytokinin was inactive. In suspension-cultured N.
      plumbaginifolia Viv., cytokinin (kinetin) was stringently required only in late
      G2 phase of the cell division cycle (cdc) and cells lacking kinetin arrested in
      G2 phase with inactive p34cdc2-like H1 histone kinase. Control of the Cdc2 kinase
      by inhibitory tyrosine phosphorylation was indicated by high phosphotyrosine in
      the inactive enzyme of arrested pith and suspension cells. Yeast cdc25
      phosphatase, which is specific for removal of phosphate from tyrosine at the
      active site of p34cdc2 enzyme, was expressed in bacteria and caused extensive in
      vitro activation of p13suc1-purified enzyme from pith and suspension cells
      cultured without cytokinin. Cytokinin stimulated the removal of phosphate,
      activation of the enzyme and rapid synchronous entry into mitosis. Therefore,
      plants can control cell division by tyrosine phosphorylation of Cdc2 but differ
      from somatic animal cells in coupling this mitotic control to hormonal signals.

PMID- 8987616
TI  - Immunocytochemical localization of phenylalanine ammonia-lyase in tissues of
      Populus kitakamiensis.
AB  - The polypeptide encoded by the partial fragment of cDNA of phenylalanine ammonia
      lyase (PAL; EC 4.3.1.5), PALcDNA1 (Osakabe et al., 1995, Plant Sci. 105: 217
      226), isolated from Populus kitakamiensis (P. sieboldii x P. grandidentata), was
      expressed in Escherichia coli cells. The polypeptide was purified and an
      antiserum raised against it. The antiserum recognized a protein of 77 kDa on
      nitrocellulose blots after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of total protein and the partially purified PAL protein from P.
      kitakamiensis. Moreover, the antiserum recognized a protein on the blot after non
      denaturing polyacrylamide gel electrophoresis of P. kitakamiensis proteins and
      this protein had PAL activity. Furthermore, the antibody inhibited PAL activity
      of extracts from stem tissues. These results showed that the antiserum against
      the partial PAL peptide recognized only the PAL subunits in extracts of P.
      kitakamiensis. Immunolocalization studies of P. kitakamiensis tissues revealed
      that the PAL protein was specifically localized in the xylem and the phloem
      fibers and no immunogold signal was found in the epidermis, the cortex, the pith,
      or the cambium of either stems or leaves.

PMID- 8987617
TI  - Evidence for the nitrate-dependent spatial regulation of the nitrate reductase
      gene in chicory roots.
AB  - Young chicory plants (Cichorium intybus L. var. Witloof) show a tenfold higher
      nitrate reductase NR activity in roots compared to leaves. Northern analysis
      revealed, besides the nitrate inducibility of the nitrate reductase gene (nia), a
      higher level of expression in the roots. By modifying the external nitrate
      concentration the NR activity in the leaves remained negligible whereas a maximal
      activity was observed in the roots when grown in the presence of 5 mM nitrate.
      Surprisingly, variation of the external nitrate concentration induced changes in
      the spatial regulation of nia within the root. In-situ hybridization mainly
      localized nia mRNA in the cortical cells of roots grown at low nitrate
      concentrations (0.2 nM). At high nitrate concentrations (5 mM), nia mRNA was more
      abundant in the vascular tissues. The root apex revealed a strong signal under
      both conditions. The isolation and characterization of the NR structural gene
      from chicory is also presented. Southern blot analysis revealed the presence of a
      single nia gene per haploid genome of chicory.

PMID- 8987618
TI  - Enzymatic properties of chorismate synthase isozymes of tomato (Lycopersicon
      esculentum Mill.).
AB  - Three plastidic chorismate synthase isozymes (CS1, CS2 and CS2 delta) of tomato
      were identified by isolation of the corresponding cDNAs. These three cDNAs are
      derived from only two genes (LeCS1 and LeCS2). This additional complexity results
      from differential splicing of the primary transcript of one of the genes (LeCS2)
      giving rise to two different transcripts (CS2 and CS2 delta transcripts). All
      three isozymes were individually expressed in Escherichia coli both as precursor
      proteins with N-terminal transit peptides and as mature proteins. Only the mature
      but not the precursor isozymes CS1 and CS2 were enzymatically active. The enzyme
      CS2 delta was unstable in E. coli. Both CS1 and CS2 were purified to near
      homogeneity and their enzymatic properties were analyzed. They differ
      substantially in their Km values for the substrate 5-enol-pyruvylshikimate 3
      phosphate (11 and 80 microM for the mature forms of CS1 and CS2, respectively).
      The two isozymes appear to be active only as oligomers, and the potential
      physiological implications of this result are discussed.

PMID- 8987619
TI  - Molecular cloning of a P-type Ca(2+)-ATPase from the halotolerant alga Dunaliella
      bioculata.
AB  - We have determined the complete primary structure of a putative P-type Ca(2+)
      ATPase from the unicellular, halotolerant alga Dunaliella bioculata. The protein
      (DBCA1) with a calculated molecular mass of 114 kDa and eight to ten putative
      transmembrane segments contains all amino acid motifs specific to the family of P
      type ATPases. Highest homology scores were obtained by comparison with
      (sarco)endoplasmic reticulum-type plant and animal Ca(2+)-ATPases (54% identity,
      70% similarity). In addition, all amino acids shown to be essential for Ca2+
      transport in animal sarcoplasmic reticulum Ca(2+)-ATPases are preserved in DBCA1.
      Significantly lower homologies were found with animal plasma membrane Ca(2+)
      ATPases (33% identity, 55% similarity), and the carboxyterminus of DBCA1 gave no
      indications of possible calmodulin-binding sites, characteristic of those
      enzymes. It is assumed that DBCA1 is a representative of the endomembrane class
      of Ca(2+)-ATPases. In Northern blot experiments with polyadenylated RNA, a 3.7-kb
      transcript was detected at levels which were very low compared with those of the
      plasma membrane H(+)-ATPase from D. bioculata (DBPMA1; Wolf et al., 1995, Plant
      Mol Biol 28: 657-666). Southern blot analyses suggest the existence of additional
      Ca(2+)-ATPase genes in the haploid genome of D. bioculata.

PMID- 8987620
TI  - Characterization of three heat-shock-protein genes and their developmental
      regulation during somatic embryogenesis in white spruce [Picea glauca (Moench)
      Voss].
AB  - Three cDNAs (PgEMB22, 27 and 29) predicted to encode low-molecular-weight (LMW)
      heat-shock proteins (HSPs) were cloned and characterized from white spruce [Picea
      glauca (Moench) Voss] somatic embryo tissues by differentially screening a
      cotyledonary embryo cDNA library. Clone PgEMB22 is predicted to encode a putative
      mitochondria-localized LMW HSP, and PgEMB27 and 29 are predicted to encode
      different cytoplasmic class II LMW HSPs, although they share 84.7% identity
      within DNA coding regions and 83.0% identity for predicted proteins. They are
      developmentally regulated during somatic embryo development and subsequent embryo
      germination, in addition they show strong response to heat-shock stress.
      Transcripts of the two kinds of hsp genes could be detected in embryogenic
      tissues before induction of embryo maturation, but subsequently increased, being
      most abundant at late embryo stages. Gene expression levels were very low or not
      detectable in germinated plantlets or needle tissues from older plants. Abscisic
      acid and polyethylene glycol, stimulators for spruce embryo maturation, could
      also induce the hsp genes.

PMID- 8987621
TI  - A two-step bioconversion process for vanillin production from ferulic acid
      combining Aspergillus niger and Pycnoporus cinnabarinus.
AB  - A two-step bioconversion process of ferulic acid to vanillin was elaborated
      combining two filamentous fungi, Aspergillus niger and Pycnoporus cinnabarinus.
      In the first step, A. niger transformed ferulic acid to vanillic acid and in the
      second step vanillic acid was reduced to vanillin by P. cinnabarinus. Ferulic
      acid metabolism by A. niger occurred essentially via the propenoic chain
      degradation to lead to vanillic acid, which was subsequently decarboxylated to
      methoxyhydroquinone. In 3-day-old cultures of P. cinnabarinus supplied with
      vanillic-acid-enriched culture medium from A. niger as precursor source, vanillin
      was successfully produced. In order to improve the yields of the process,
      sequential additions of precursors were performed. Vanillic acid production by A.
      niger from ferulic acid reached 920 mg1-1 with a molar yield of 88% and vanillin
      production by P. cinnabarinus from vanillic acid attained 237 mg1-1 with a molar
      yield of 22%. However, the vanillic acid oxidative system producing
      methoxyhydroquinone was predominant in P. cinnabarinus cultures, which explained
      the relatively low level in vanillin.

PMID- 8987622
TI  - Cloning, sequencing, and expression of the cellulase genes of Humicola grisea
      var. thermoidea.
AB  - We have cloned an endoglucanase (EGI) gene and a cellobiohydrolase (CBHI) gene of
      Humicola grisea var. thermoidea using a portion of the Trichoderma reesei
      endoglucanase I gene as a probe, and determined their nucleotide sequences. The
      deduced amino acid sequence of EGI was 435 amino acids in length and the coding
      region was interrupted by an intron. The EGI lacks a hinge region and a cellulose
      binding domain. The deduced amino acid sequence of CBHI was identical to the H.
      grisea CBHI previously reported, with the exception of three amino acids. The H.
      grisea EGI and CBHI show 39.8% and 37.7% identity with T. reesei EGI,
      respectively. In addition to TATA box and CAAT motifs, putative CREA binding
      sites were observed in the 5' upstream regions of both genes. The cloned
      cellulase genes were expressed in Aspergillus oryzae and the gene products were
      purified. The optimal temperatures of CBHI and EGI were 60 degrees C and 55-60
      degrees C, respectively. The optimal pHs of these enzymes were 5.0. CBHI and EGI
      had distinct substrate specificities: CBHI showed high activity toward Avicel,
      whereas EGI showed high activity toward carboxymethyl cellulose (CMC).

PMID- 8987623
TI  - Calcium influences the stability and conformation of rotavirus SA11 glycoprotein
      VP7 expressed in Dictyostelium discoideum.
AB  - We have previously reported expression of the rotavirus outer capsid
      glycoprotein, VP7, in the relatively new expression host, Dictyostelium
      discoideum. To optimise yields of recombinant VP7, we examined the role of Ca2+
      since stability of both VP7 and mature rotavirus during a rotavirus infection are
      calcium-dependent. Low micromolar levels of free extracellular Ca2+ were required
      to maximise yields of VP7 in D. discoideum whilst levels of VP7 were reduced
      following depletion of intracellular Ca2+ reserves using A23187 and EGTA.
      Immunoblot analysis suggested that VP7 was being degraded in an intracellular
      compartment. Immunoprecipitation with a conformation-dependent neutralising
      antibody confirmed that EGTA-induced Ca2+ chelation alters the conformation of
      VP7. These results suggest that stability of VP7 is dependent on maintaining
      adequate levels of intracellular Ca2+ and that conformational changes in VP7
      which occur following depletion of Ca2+ reserves induce rapid proteolysis of the
      protein. Since these results establish conditions for expressing optimal levels
      of VP7 in the correct conformation they have important implications for the
      development of a subunit vaccine based on recombinant VP7.

PMID- 8987624
TI  - Continuous production of high degree casein hydrolysates by immobilized proteases
      in column reactor.
AB  - The enzymatic complete hydrolysis of casein was investigated by using immobilized
      endopeptidase and exopeptidase packed in the jacketed column reactors. The mass
      transfer efficiency of proteins was improved by using sliced shrimp chitin hull
      as enzyme support, which formed a network structure inside the column reactor
      that prevented the formation of protein precipitate and increased the line flow
      rate of protein solution. The specificity of the protease was of crucial
      importance for both the hydrolysis degree and the free amino acid content of the
      hydrolysates. Of the enzymes, tested, the immobilized A. oryzae protease was the
      most effective enzyme in breaking down the casein molecules and releasing the
      free amino acid from casein hydrolysates. The immobilized pancreatic and kidney
      exopeptidase could lead to a 20% increase of free amino acids. The free amino
      acid content of casein hydrolysates was 34.81% after processing and could reach
      to 64% if the column length was doubled, but 100% hydrolysis was impossible as
      the reverse reaction was also taking place. The casein hydrolysates was
      characterized by its high degree of hydrolysis and high content of free amino
      acids. It can be applied in infant formula, element diet, and as a protein
      ingredient for food industry.

PMID- 8987625
TI  - Synthesis of soluble rubella virus spike proteins in two lepidopteran insect cell
      lines: large scale production of the E1 protein.
AB  - The two envelope glycoproteins of rubella virus (RV), E1 of 58 kDa and E2 of 42
      47 kDa, were individually expressed in lepidopteran Spodoptera frugiperda as well
      as in Trichoplusia ni insect cells using baculovirus vectors. The authentic
      signal sequences of E1 and E2 were replaced with the honeybee melittin signal
      sequence, allowing efficient entrance into the secretory pathway of the insect
      cell. In addition, the hydrophobic transmembrane anchors at the carboxyl termini
      of E1 and E2 proteins were removed to enable secretion rather than maintenance in
      the cellular membranes. Synthesis of the recombinant proteins in the absence and
      presence of tunicamycin revealed that both E1 and E2 were glycosylated with
      apparent molecular weights of 52 kDa and 37 kDa, respectively. Recombinant E2
      appeared to be partially secreted, whereas E1 was essentially found inside the
      infected insect cell. The E1 protein was produced in large scale using a 10-1
      bioreactor and serum-free medium (SFM). Purification of the recombinant protein
      product was performed from cytoplasmic extracts by ammonium sulphate
      precipitation followed by Concanavalin A affinity chromatography. This type of
      purified recombinant viral glycoproteins may be useful not only in diagnostic
      medicine or for immunization, but should enable studies designed to solve the
      structure of the virus particle.

PMID- 8987626
TI  - Thermostabilization of protective antigen--the binding component of anthrax
      lethal toxin.
AB  - Protective antigen (PA) is the binding component of anthrax lethal toxin produced
      by Bacillus anthracis, and constitutes a major ingredient of the vaccine against
      anthrax. PA and lethal factor when added together are cytolytic to mouse
      macrophages and J774G8 macrophage cell line. This in vitro lethal toxicity assay
      is very useful in understanding the molecular mechanism of action of lethal
      toxin. Effective utilization of PA is, however, hampered due to its
      thermolability. On prolonged storage at 37 degrees C, PA was found to lose its
      activity almost completely. The effect of solvent additives like trehalose,
      sorbitol, xylitol, sodium citrate and magnesium sulphate on the thermal
      stabilization of PA was examined. The results indicated an increase in the
      stability of PA when the incubation at 37 degrees C was carried out in the
      presence of solvent additives used in the 1-3 M range. Magnesium sulphate helped
      retain the activity up to 82.7% against the control in which no additive was
      used, as judged by cytolytic assay using J774G8 macrophage cell line. Trehalose
      or sodium citrate also showed an appreciable protection of PA activity, while
      sorbitol or xylitol were not very effective. Competitive binding assay using
      radiolabeled PA showed that PA had lost capacity of binding to macrophage cells
      on prolonged incubation at 37 degrees C. Circular dichroism results at 4, 18, and
      37 degrees C indicated an increase in secondary structure at 37 degrees C
      relative to that at 4 or 18 degrees C, supporting the activity data.

PMID- 8987627
TI  - Bioreactor studies on temperature induction of the Q- mutant of bacteriophage
      lambda in Escherichia coli.
AB  - The parasite-host interactions between bacteriophage lambda (denoted as lambda)
      and Escherichia coli bacteria were studied in different bioreactor systems.
      Although the replicated lambda-DNA of Q- mutant remains naked for a longer time
      to reach a high gene expression, the epidemic of lambda-infection and the
      coevolutionary host-phage relations limit the temperature induction efficiency.
      The temperature induction is strongly dependent upon the susceptible population
      density at which lambda-infection is activated. Maximum beta-galactosidase
      expression occurs at the threshold of the infection system. According to this
      concept, the lethal level of parasitic lambda to hosts is approx. 5 x 10(6)
      pfu/ml. Since a higher phage lambda burden is exerted upon host cells at a low
      ODsh, the system moves towards virulence reduction for total survival. Prey
      predator isocline analysis is used to consider the stability of the outcome of
      infection. The host growth has a destabilizing effect at lower population
      densities and a stabilization effect at higher population. Based upon the
      predictions, a substrate enrichment enhances bacterial growth and reporter
      protein production. However, the operations still need to follow the trajectory
      of threshold tie line to guarantee maximal productivity. Since the washout of
      infected cells reduces induction performance in continuous cultures, a batch mode
      of operation is better than continuous stirred tank reactor (CSTR) mode to
      achieve high gene expression. The threshold cell density regulates induction
      performances and therefore produces the optimal gene expression by maintaining
      maximal viable cells that provide sufficient resources for lambda expression.

PMID- 8987628
TI  - Development of an on-line control system for the cultivation of animal cells in a
      hollow-fiber reactor using flowing injection analysis and a visual programming
      language.
AB  - A system for the independent control of ammonia and glutamine in a hollow-fiber
      reactor has been developed. On-line analysis of the two chemical species was
      performed using FIA. A custom-made program has been written to fully automate the
      FIA, to perform measurements, calibrations and data acquisition, and to activate
      two peristaltic feed pumps. Diagnostic tests were also automatically performed in
      order to identify, and in some cases eliminate, erroneous measurements and
      calibrations due to instrument failures. For this purpose, a visual programming
      language (LabVIEW) has been chosen. Ammonia concentration was controlled by
      varying the medium supply rate to the hollow-fiber reactor which was shown to
      behave like an ideal-stirred tank reactor. The glutamine concentration was
      controlled through the intermittent activation of a pump delivering a
      concentrated solution of this species to the reactor. This control system was
      tested with a culture of hybridoma cells at three different ammonia and one
      glutamine set-points. The hollow-fiber reactor was successfully operated
      automatically for more than 1200 h with ammonia and glutamine concentrations
      accurately controlled at non-limiting levels. The visual programming environment
      was found to be reliable and highly suitable for the development of custom
      programs for bioprocess control.

PMID- 8987629
TI  - Physiology of Saccharomyces cerevisiae during cell cycle oscillations.
AB  - Synchronized populations of Saccharomyces cerevisiae CBS 426 are characterized by
      autonomous oscillations of process variables. CO2 evolution rate, O2 uptake rate
      and heat production rate varied by a factor of 2 for a continuous culture grown
      at a dilution rate of 0.10 h-1. Elemental analysis showed that the carbon mass
      fraction of biomass did not change. Since the reactor is not at steady state, the
      elemental and energy balances were calculated on cumulated quantities, i.e. the
      integral of the reaction rates. It was possible to show that carbon, degree of
      reduction and energy balances matched. Application of simple mass balance
      principles for non-steady state systems indicated that oscillations were
      basically characterized by changes in biomass production rate. In addition, the
      amount of intermediates, e.g. ethanol or acetate, produced or consumed was
      negligible. Growth rate was low during the S-phase (0.075 h-1) and high during
      the G2, M and G1 phases (0.125 h-1) for a constant dilution rate of 0.10 h-1.
      However, nitrogen, ash, sulfur and potassium content showed systematic increases
      during the S-phase (bud initiation). Cell component analyses showed that changes
      in cellular fractions during oscillations (storage carbohydrate content decreased
      during the S-phase) were due to changes in production rates, particularly for
      protein and carbohydrates. Nevertheless, using the data evaluation techniques for
      dynamic systems presented here, it was shown that storage carbohydrates are not
      consumed during the S-phase. Only the synthesis rate of the different cell
      components changed depending on position in cell cycle. The growth process may be
      divided into two phenomena: the formation of new cells during mitosis with a low
      yield, and size increase of new born cells with high yield. Both kinetic and
      stoichiometric coefficients varied with the position in the oscillation: the
      results showed that biomass structure changed and that specific growth rate, as
      well as biomass yield, varied by +/- 25% during the oscillation.

PMID- 8987630
TI  - Model-based automation of baker's yeast production.
AB  - An on-line model, estimating key state variables in bioprocesses, is utilized for
      control of fed-batch baker's yeast production. The state estimates are produced
      by balances and phenomenological expressions combined with on-line measurements.
      The goal of the control strategy is to maintain the highest possible glucose flux
      that can be entirely respiratively assimilated by the cells, resulting in the
      highest possible yeast growth without formation of metabolic products, such as
      acetic acid and ethanol. Stepwise improvement of the control algorithm is carried
      out in order to find a strategy to avoid undesired, irreversible metabolic
      pathways. In the final algorithm, such undesired changes in metabolism are
      predicted from an estimate of intracellular storage carbohydrates. A considerable
      decrease in the estimate indicates future metabolic changes at a time early
      enough to avoid them. At maximal yield, a growth rate near the highest possible
      is obtained in laboratory-scale Saccharomyces cerevisiae cultivations with the
      control strategy developed.

PMID- 8987632
TI  - Progress towards a new wave of immune-based therapeutics.

PMID- 8987631
TI  - Characterization of a protease deficient strain of Penicillium roqueforti
      generated by heterologous plasmid integration: potential use for protein
      production.
AB  - A strain of Penicillium roqueforti was transformed with a plasmid which confers
      resistance to phleomycin. Stable transformants were selected. They all present a
      high resistance to the antibiotic. Their proteolytic activity was tested. One
      transformant is a proteolytic deficient strain unable to degrade casein. It is
      characterized by a tandem integration of the transformant vector in one site of
      the genome. The extracellular proteins profile of the strain reveals the absence
      of a 43 kDa polypeptide which probably corresponds to the aspartyl protease of
      Penicillium roqueforti. The aspA gene which encodes aspartyl protease is not
      expressed in the transformant and Southern analyses show that the aspA gene is
      not disrupted by the transformation vector.

PMID- 8987633
TI  - Urine-based diagnostic technologies.
AB  - The worldwide dissemination of infectious agents has created a demand for simple
      diagnostic tests. Urine-based testing makes use of non-invasive collection of
      specimens, and there is no need for expensive facilities and equipment, or for
      highly trained personnel. As urine antibodies retain activity under normal
      conditions of transport and storage, such tests appear to have widespread
      application. Urine-based antibody tests have also indicated a compartmentalized
      antibody response to HIV-1 infection. Urine studies suggest that antibodies to
      the products of endogenous viral genes may be involved in the pathogenesis of
      chronic diseases of suspected viral etiology.

PMID- 8987635
TI  - Identifying structure-function relationships in four-helix bundle cytokines:
      towards de novo mimetics design.
AB  - Many cytokines (growth-factor proteins) are constructed from a common four-helix
      bundle structural framework. Rapid advances have been made in relating the
      structure and function of a growing number of four-helix bundle cytokines. This
      understanding opens the way to design de novo mimetics through such strategies as
      cytokine hybrids, structure-excerpted scaffolds and contact residue topology
      mimics. These may provide leads for agonists and antagonists of cell growth and
      differentiation.

PMID- 8987634
TI  - Evaluation of hepatitis C virus protein epitopes for vaccine development.
AB  - Infection with hepatitis C virus (HCV) leads to viral persistence and chronic
      disease in a very high proportion of cases, despite a broad immunological
      response to viral proteins. These responses may thwarted by the high rate of
      mutation, which leads to the generation of 'escape' variants of HCV that persist
      as a quasi-species in infected individuals. The specificity of the immuno
      response of infected patients suggests that responses directed at certain viral
      epitopes may be associated with less aggressive disease and, possibly, good
      interferon response and virus clearance. The identification of such epitopes may
      hold the key for future development both of prophylactic and therapeutic
      vaccines.

PMID- 8987636
TI  - Antisense oligonucleotides: towards clinical trials.
AB  - Antisense oligonucleotides have the ability to selectively block disease-causing
      genes, thereby inhibiting production of disease-associated proteins. The
      specificity and application of antisense oligonucleotides have been strongly
      validated in animal models for various disease targets. Based on the
      pharmacological, pharmacodynamic and pharmacokinetic profiles, the first
      generation of antisense oligonucleotides--phosphorothioates--have reached the
      stage of human clinical trials for various diseases. While ongoing human clinical
      trials are being carried out to further establishing the safety and efficacy of
      these oligonucleotides, the experience gained is providing a basis for designing
      a second generation of antisense oligonucleotides.

PMID- 8987637
TI  - Hematopoietic cell culture therapies (Part II): Clinical aspects and
      applications.
AB  - High-dose chemotherapy, followed by hematopoietic stem cell transplantation,
      holds significant promise for increasing the probability of long-term remission
      and possibly cure in a variety of cancers. Hematopoietic cell culture, or ex vivo
      expansion of hematopoietic cells, may play a significant role in reducing the
      danger and expense associated with the transplantation procedure. Phase I
      clinical trials have shown that ex vivo expanded cells have no significant
      toxicities, and some benefits. Ex vivo expansion of hematopoietic cells is likely
      to find other applications in gene therapy, tumor purging, production of
      dendritic cells for immunotherapy and the production of mature blood cells for
      transfusion therapies.

PMID- 8987638
TI  - Towards inexpensive DNA diagnostics.
AB  - Methodologies to obtain DNA sequence information efficiently and accurately will
      provide the basis for a broad spectrum of economical products and applications to
      a variety of industrial sectors, in addition to healthcare. Such technologies
      will build upon the evolving molecular biology and instrumentation base that is
      serving a specific research market. This will require the efficient integration
      of technical advances in microchemistry, micromachining, separation technologies,
      detection systems, microelectronics and information technology, and will involve
      the expertise of engineers, physicists, chemists, mathematicians, computer
      scientists and molecular biologists. The biotechnology, microelectronics,
      software, instrumentation, pharmaceutical and fine chemical industries will be
      vital to this development.

PMID- 8987639
TI  - The development of microfabricated arrays for DNA sequencing and analysis.
AB  - Microfabricated arrays of immobilized oligodeoxynucleotide probes are proving to
      be a powerful tool for rapidly generating sequence data via hybridization. These
      arrays are made either by immobilization of the probe post-synthetically, or by
      in situ synthesis of the probe. Hybridization of the target is easily achieved on
      the arrays, with analysis proceeding either by direct detection, or through
      enzyme-mediated detection; analysis of the hybridization pattern yields sequence
      information about the target. Such facile and rapid data acquisition will assist
      the challenging task of sequencing the human genome, and also will lead to a new
      generation of diagnostic assays.

PMID- 8987640
TI  - The occurrence of killer, sensitive, and neutral yeasts in Brazilian Riesling
      Italico grape must and the effect of neutral strains on killing behaviour.
AB  - The occurrence of killer toxins amongst yeast in Brazilian Riesling Italico grape
      must was investigated by using the sensitive strain EMBRAPA-26B as a reference
      strain at 18 degrees C and 28 degrees C. From a total of 85 previously isolated
      yeasts, 21 strains showed ability to kill the sensitive strain on unbuffered
      grape must/agar (MA-MB) and 0.1 M citrate/phosphate-buffered yeast
      extract/peptone/dextrose/agar (YEPD-MB) media both supplemented with 30 mg/l
      methylene blue. The killer activity of only four yeasts depended on the
      incubation temperature rather than the medium used. At 28 degrees C, the strains
      11B and 53B were not able to show killer action. On the other hand, strains 49B
      and 84B did not kill the sensitive yeast at 18 degrees C. The killer strain
      EMBRAPA-91B and a commercial wine killer yeast K-1 were employed to examine the
      sensitivity of the isolated yeasts on YEPD-MB and MA-MB at 18 degrees C. The
      sensitivity and neutral characteristics of yeasts were shown to be dependent on
      the medium and the killer strain. Interactions, including K-R-, K-R+ and K+R+
      strains, simultaneously, have revealed that some K-R+ strains appear to protect
      the K-R- strain against the killer toxin. Sensitive dead cells, although to a
      less extent, also exhibited similar protection. Kinetic studies have shown that
      the maximum specific growth rates were higher for the 20B YEPD-MB-sensitive
      strains (mu(max) = 0.517 h-1) than for both the 91B (mu(max) = 0.428 h-1) and K-1
      (mu(max) = 0.466 h-1) killer strains. The protective capacity of neutral or
      sensitive cells that contaminate a fermentation, as well as the higher maximum
      specific growth rate of sensitive yeasts, besides other factors, may preclude the
      dominance of a killer strain. This protective capacity may also reduce the risk
      of a sensitive inoculum being killed by wild-type killer yeasts in open non
      sterile fermentation.

PMID- 8987642
TI  - Selection of an adhesive phenotype of Streptococcus salivarius subsp.
      thermophilus for use in fixed-bed reactors.
AB  - Streptococcus salivarius subsp. thermophilus was cultivated in a chemostat in
      order to obtain an adhesive phenotype of this strain. When the system was
      operated at low dilution rates (D < 0.2 h-1) for about 4 weeks, the strain formed
      a visible film on the surface of the culture vessel. The biofilm cells were not
      washed out even when dilution rates were increased (D = 6.9 h-1), and this
      resulted in a high biomass productivity (P = 4.1 g1(-1) h-1). On the other hand,
      when the culture was grown at dilution rates faster than 0.2 h-1, only the free
      suspended cells were present in the culture broth, and were washed out at
      velocities of about 1.0 h-1. The biomass productivity was consequently lower (P =
      1.33 g1(-1) h-1) than in the previous case. The selected adhesive phenotype was
      grown on different glass beads and the possibility of lactate fermentation in a
      continuous and semicontinuous mode was demonstrated.

PMID- 8987641
TI  - Continuous production of ethanol using yeast cells immobilized in preformed
      cellulose beads.
AB  - Saccharomyces cerevisiae cells were immobilized on preformed cellulose beads by
      adsorption. The fermentation capacity of the immobilized yeast cells was found to
      be practically independent of the hydrogen ion concentration between pH 3.1 and
      6.25. The fermentation capacity was maximal at 30 degrees C. The immobilized
      yeast cells were used for continuous production of ethanol in a fluidized-bead
      reactor. The average values characteristic for the process were an ethanol
      concentration of 41.9 +/- 0.1 g1(-1), a fermentation efficiency of 82.9 +/- 2.1%
      and a volumetric productivity of 3.94 +/- 0.52 g1(-1) h-1.

PMID- 8987643
TI  - A microcarrier culture method for the production of large quantities of viable
      Chlamydia pneumoniae.
AB  - We studied the propagation of Chlamydia pneumoniae strain TW-183 in HEp2 cells
      grown on microcarrier beads. Infection of the cells in microcarrier culture was
      optimized by addition of 7.5% polyethylene glycol 4000 (PEG4000) during
      adsorption. The yield in microcarrier culture was similar to that of microtitre
      plate culture using centrifugation-assisted infection (120 x 10(6) and 225 x
      10(6) bacteria/10(6) HEp2 cells respectively), as was the burst size (505 and 449
      bacteria produced/infecting bacterium respectively). However, up to 64% savings
      in labour time and 27% saving in culture medium were achieved if the microcarrier
      culture method was used instead of the microtitre-plate culture method. The
      optimal yield of viable bacteria could only be achieved at a narrow range of
      multiplicities of infection (0.24 - 1.14 inclusion-forming units/cell),
      independent of the mode of infection (centrifugation-assisted infection of
      PEG4000-facilitated infection by adsorption) and independent of incubation
      temperature (35 degrees C or 37 degrees C). The yield of microcarrier cultures
      was the same at an incubation temperature of 35 degrees C or 37 degrees C in
      contrast to an increased production at 35 degrees C in the microtitre-plate
      culture method using centrifugation-assisted infection. In conclusion, the
      microcarrier culture method is useful to produce large quantities of viable
      Chlamydia pneumoniae economically.

PMID- 8987644
TI  - Efficient selection of hygromycin-B-resistant Yarrowia lipolytica transformants.
AB  - The yeast Yarrowia lipolytica was shown to be sensitive to the aminoglycoside
      antibiotic hygromycin B. Spontaneous resistants appeared at a frequency of (2-5)
      x 10(-7) in media containing 100 mg/l drug. In order to develop a new selective
      marker for the transformation of this yeast, we constructed new plasmids
      expressing the Escherichia coli hygromycin-resistance gene (hph) under the
      control of the promoter and terminator sequences of the strongly expressed XPR2
      gene of Y. lipolytica. Direct selection of hygromycin-B-resistant transformants
      on complete medium was very efficient and resulted in transformation frequencies
      comparable to those observed with conventional auxotrophic markers. This new
      marker can be used for integrating single copies of plasmid and for gene
      disruption and provides a convenient tag for genetic studies.

PMID- 8987645
TI  - A cellulase gene from a new alkalophilic Bacillus sp. (strain N186-1). Its
      cloning, nucleotide sequence and expression in Escherichia coli.
AB  - Several alkalophilic Bacillus spp. strains were selected for their capacity to
      produce alkaline cellulases. Culture supernatants of these strains showed optimal
      cellulase activities between pH 8 and 9 and they were stable from pH 6 to pH 12.
      A cellulase gene (celB1) from the alkalophilic Bacillus sp. strain N186-1 was
      cloned in Escherichia coli using polymerase chain reaction techniques. The cloned
      gene was present in a 2.539-bp HindIII fragment and its nucleotide sequence was
      determined. The coding sequence showed an open-reading frame encoding 389 amino
      acids. The amino acid sequence, deduced from the nucleotide sequence, permitted
      us to include it in family 5 (or A) of the glycosyl hydrolases. The complete open
      reading frame of celB1 was cloned in the plasmid pET-11d and expressed in E. coli
      BL21 (DE3), in which a protein of 39 kDa was obtained in the cytoplasm; however,
      no endoglucanase activity was detected. A second construction in pET-12a allowed
      the production of a 39-kDa protein located in the periplasmic space of E. coli
      that had endoglucanase activity. The protein produced has optimal activity at pH
      7 and 50 degrees C and it retains more than 70% of its activity after incubation
      for 1 h at pH 12.

PMID- 8987646
TI  - Cometabolic degradation of 4-chlorophenol by Alcaligenes eutrophus.
AB  - Alcaligenes eutrophus was grown in batch cultures using either phenol as a sole
      substrate or mixtures of phenol and 4-chlorophenol. Phenol was found to be the
      sole source for carbon and energy while 4-chlorophenol was utilized only as a
      cometabolite. Maximum growth rates on phenol reached only 0.26 h-1, significantly
      below the growth rates reported earlier with Pseudomonas putida. The cometabolite
      was found to decrease biomass yield and increase lag time before logarithmic
      growth occurred. Both phenol and 4-chlorophenol were found to inhibit the growth
      rate linearly with maximum concentrations of 1080 ppm and 69 ppm respectively,
      beyond which no growth occurred. The best-fit parameters are incorporated into a
      simple, dynamic (i.e. time-varying) model capable of predicting all the batch
      growth conditions presented here. It is shown that P. putida is capable of faster
      bioremediation when phenol is the sole carbon source or for mixed substrates with
      low concentrations of the cometabolite, but for high concentrations of 4
      chlorophenol, A. eutrophus becomes superior because of the long lag times that
      occur in the Pseudomonas species.

PMID- 8987647
TI  - Growth and fermentation responses of Selenomonas ruminantium to limiting and non
      limiting concentrations of ammonium chloride.
AB  - The objective of this study was to assess fermentation product, growth rate and
      growth yield responses of Selenomonas ruminantium HD4 to limiting and non
      limiting ammonia concentrations. The ammonia half-inhibition constant for S.
      ruminantium in batch culture was 296 mM. Cells were grown in continuous culture
      with a defined ascorbate-reduced basal medium containing either 0.5, 5, 25, 50,
      100 or 200 mM NH4Cl and dilution rates were 0.07, 0.14, 0.24 or 0.40 h-1. Ammonia
      was the growth-limiting nutrient when 0.5 mM NH4Cl was provided and the half
      saturation constant was 72 microM. Specific rates of glucose utilization and
      fermentation acid carbon formation were highest for 0.5 mM NH4Cl. Lactate
      production (moles per mole of glucose disappearing) increased at the fastest
      dilution rate (0.40 h-1) for 5.0 mM NH4Cl while acetate and propionate decreased
      when compared to slower dilutions (0.07 and 0.14 h-1). Lactate production
      remained low while acetate and propionate remained high for all dilution rates
      when NH4Cl concentrations were 25 mM or greater. Yield (Y(Glc) and Y(ATP)) were
      nearly doubled when NH4Cl was increased from 0.5 mM (25.1 g cells/mol glucose
      used and 13.9 g cells/mol ATP produced respectively) to the higher
      concentrations. Y(Glc) was highest at 25 mM and 50 mM NH4Cl (48.2 cells/mol and
      43.1 cells/mol respectively) as was Y(ATP) (23.2 cells/mol and 20.8 cells/mol
      respectively). Y(NH3) was highest at the lowest NH4Cl concentration. The maximal
      fermentation product formation rate occurred at a growth-limiting ammonia
      concentration, while maximal glucose and ATP bacterial yields occurred at non
      growth-limiting ammonia concentrations. Given the growth response of this ruminal
      bacterium, it is possible that maximization of ruminal bacterial yield may
      necessitate sacrificing the substrate degradation rate and vice versa.

PMID- 8987648
TI  - The effects of pantothenate deficiency and acetate addition on anaerobic batch
      fermentation of glucose by Saccharomyces cerevisiae.
AB  - Physiological effects of deficiency of pantothenate, a necessary precursor in the
      synthesis of coenzyme A, were studied using the yeast strain Saccharomyces
      cerevisiae CBS 8066. Cells were grown on defined media in anaerobic batch
      cultures with glucose (50 g/l) as the carbon and energy source. Batch cultures
      containing more than 60 micrograms/l pantothenate showed no significant
      differences with respect to growth rates and product yields. However, with an
      initial pantothenate concentration at 30 micrograms/l, the average glucose
      consumption rate was 50% lower than in rich medium and, at even lower
      concentration of pantothenate, the culture did not consume all the glucose in the
      medium. Furthermore, pantothenate deficiency caused the acetate and pyruvate
      yields to increase and the biomass yield to decrease, compared to the yields in
      pantothenate-rich medium. The increased acetate formation could be counteracted
      by initial addition of acetate to the medium, and thereby the glycerol yield
      could be decreased. An initial addition of acetate of 1.6 g/l to pantothenate
      deficient medium (30 micrograms/l) caused a 35% decrease in glycerol yield and a
      6% increase in ethanol yield. Furthermore, the time required for complete
      conversion of the glucose decreased by 40%. Acetate addition affected the acetate
      and glycerol yields in a similar way in pantothenate-rich medium (1000
      micrograms/l) also.

PMID- 8987649
TI  - Fermentation of molasses using a thermotolerant yeast, Kluyveromyces marxianus
      IMB3: simplex optimisation of media supplements.
AB  - The use of molasses as a substrate for ethanol production by the thermotolerant
      yeast Kluyveromyces marxianus var. marxianus was investigated at 45 degrees C. A
      maximum ethanol concentration of 7.4% (v/v) was produced from unsupplemented
      molasses at a concentration of 23% (v/v). The effect on ethanol production of
      increasing the sucrose concentration in 23% (v/v) molasses was determined.
      Increased sucrose concentration had a similar detrimental effect on the final
      ethanol produced as the increase in molasses concentration. This indicated that
      the effect may be due to increased osmotic activity as opposed to other
      components in the molasses. The optimum concentration of the supplements
      nitrogen, magnesium, potassium and fatty acid for maximum ethanol production rate
      was determined using the Nelder and Mead (Computer J 7:308-313, 1965) simplex
      optimisation method. The optimum concentration of the supplements were 0.576 g1(
      1) magnesium sulphate, 0.288 g1(-1) potassium dihydrogen phosphate and 0.36%
      (v/v) linseed oil. Added nitrogen in the form of ammonium sulphate did not affect
      the ethanol production rate.

PMID- 8987650
TI  - Extracellular production of a Serratia marcescens serine protease in Escherichia
      coli.
AB  - The Serratia marcescens serine protease (SSP) is one of the extracellular enzymes
      secreted from this Gram-negative bacterium. When the ssp gene, which encodes a
      SSP precursor (preproSSP) composed of a typical NH2-terminal signal peptide, a
      mature enzyme domain, and a large COOH-terminal pro-region, is expressed in
      Escherichia coli, the mature protease is excreted through the outer membrane into
      the medium. The COOH-terminal pro-region, which is integrated into the outer
      membrane, provides the essential function for the export of the mature protein
      across the outer membrane. This is a very simple pathway, in contrast to the
      general secretory pathway exemplified by the secretion of a pullulanase from
      Klebsiella oxytoca, in which many separately encoded accessory proteins are
      required for the transport through the outer membrane. Moreover, the NH2-terminal
      region of 71 amino acid residues of the COOH-terminal pro-sequence plays an
      essential role, as an "intramolecular chaperone," in the folding of the mature
      enzyme in the medium. In addition to ssp, the S. marcescens strain contains two
      ssp homologues encoding proteins similar to SSP in amino acid sequence and size,
      but with no protease activity. Characterization of the homologue proteins and
      chimeric proteins between the homologues and SSP, all of which are produced in E.
      coli, has shown that they are membrane proteins that are localized in the outer
      membrane in the same manner as for SSP. By use of the COOH-terminal domain of
      SSP, pseudoazurin was exported to the cell surface of E. coli, which proves the
      usefulness of the SSP secretory system in the export of foreign proteins across
      the outer membrane.

PMID- 8987651
TI  - Effect of acetylation of ovalbumin on its adsorption behavior at solid/liquid
      interface.
AB  - This paper reports the effect of modification of lysine residues on the
      adsorption of ovalbumin at alumina/water interface. It has been shown that the pH
      dependence of the adsorption changes on acetylation of lysine. Thus at pH 7.6
      acetylated ovalbumin does not show any affinity for alumina surface although
      unmodified protein does. It seems that although electrostatic interactions are
      operative, surface unfolding of proteins and surface hydrophobicity of protein
      also control the adsorption of ovalbumin onto alumina.

PMID- 8987653
TI  - Detection of protein A produced by Staphylococcus aureus with a fiber-optic-based
      biosensor.
AB  - Staphylococcus aureus is a pathogen important in causing human infections and
      intoxication. A sensitive fiber-optic that produces evanescent waves was
      developed for the detection of protein A, a product secreted only by S. aureus.
      In the immunosensor, a 40-mV argon-ion laser that generated laser light at 488 nm
      was used together with plastic optical fiber and antibodies to protein A were
      physically adsorbed onto the fiber. The principle of the detection involved a
      sandwich immunoassay with fluorescein isothiocyanate conjugated with anti
      (protein A) immunoglobulin G to produce signals of the antigen-antibody reaction.
      The detection limit was 1 ng of protein A per milliliter. The fiber-optic
      immunosensor could be used for rapid and specific detection of S. aureus in
      clinical specimens and foods.

PMID- 8987652
TI  - Molecular cloning of a novel gene, dtsR, which rescues the detergent sensitivity
      of a mutant derived from Brevibacterium lactofermentum.
AB  - Several strains of Corynebacterium and Brevibacterium are known for their ability
      to secrete large amounts of amino acids, especially L-glutamate. We focused on
      the mechanism of L-glutamate secretion triggered by a detergent, namely
      polyoxyethylenesorbitan monopalmitate (PESP). A mutant strain, AJ11060, derived
      from Brevibacterium lactofermentum ATCC 13869 indicates the sensitivity to PESP.
      A multicopy suppresser gene that compliments the sensitivity of AJ11060 to the
      detergent was derived from a gene library of B. lactofermentum AJ12036. A 2855-bp
      DNA fragment was cloned and sequenced. An open reading frame was found that coded
      for the rescuer gene of the sensitivity to PESP of AJ11060 and was designated
      dtsR. The expression of the dtsR gene in B. lactofermentum was confirmed by using
      anti-DtsR antibody. The deduced DtsR protein indicated significant homology with
      some biotin enzymes such as the beta chain of propionyl-CoA carboxylase from rat
      (48.3%) and human (48.7%), or a 12S chain of methylmalonyl-CoA
      carboxyltransferase from Propionibacterium freudenreichii (43.1%).

PMID- 8987655
TI  - Metabolism of lysine, threonine, and leucine in growing rats on gluten or zein
      diets at various dietary protein levels.
AB  - The metabolic fates of the carbon skeletons of leucine, lysine, and threonine
      were studied in growing rats on the diets containing graded levels of protein
      calorie percentages (10, 20, 30, and 40 PC%) by use of either gluten or zein at
      4100 kcal of metabolizable energy per kg of diets. In growth experiment for 21
      days, body weight gain, food intake, and body fat increased at higher PC% in the
      gluten diets, but rats given zein did not maintain their initial weight even at
      40 PC%. The concentration of plasma free lysine remained low with the zein diets,
      but plasma threonine increased at 10 and 20 PC% in the gluten and zein diets,
      respectively. Plasma leucine increased as the protein level increased either
      dietary protein. More than 70% of 14C was incorporated into body protein 12 h
      after an intraperitoneal injection of labeled lysine in all groups, but little
      14CO2 was expired in rats on the gluten and zein diets. About 79% of 14C
      threonine was incorporated into body protein in rats given the gluten and zein
      diets at 10 PC%, but the values were gradually decreased with increasing the
      dietary protein levels. Some 40-50% of 14C-leucine was incorporated into the body
      protein in rats given the gluten diets, and the values for the zein diets were
      extensively decreased in the higher PC% groups where the expired 14CO2 was
      inversely increased to a great extent. These results showed that, when a specific
      amino acid was limiting or deficient in the diet, the major portion of the
      labeled amino acid was utilized for body protein synthesis and little was
      oxidized to carbon dioxide, whereas the oxidative degradation of essential amino
      acid other than limiting one was increased and the efficiency of the amino acid
      utilization was relatively decreased.

PMID- 8987654
TI  - Acid lipase inhibitor in chicken plasma identified as apolipoprotein A-I.
AB  - We have reported a inhibitor of acid lipases in liver lysosomes and erythrocytes
      from chickens [M. Fujii et al., Int. J. Biochem., 22, 895-898 (1990)]. In this
      paper, the properties of the inhibitor were described in comparison with those of
      apo A-I of chicken. The purified inhibitor migrated with the same mobility on SDS
      PAGE as apo A-I, and had a molecular weight of 27,000. The peptide map from the
      lipase inhibitor was similar to that of apo A-I. Antibodies to the acid lipase
      inhibitor also reacted with apo A-I. Apo A-I inhibited the acid lipase activities
      of liver lysosomes and erythrocytes from chickens as strongly as the lipase
      inhibitor. The N-terminal amino acid sequence of lipase inhibitor was identical
      to that of apo A-I as far as residue 20. The amino acid sequence of peptides
      obtained from the inhibitor by cleavage with CNBr corresponded to internal
      sequence of apo A-I, and so the CNBr-peptides were derived by cleavage after the
      methionine residues in apo A-I. The findings showed that the inhibitor of the
      acid lipases in liver lysosomes and erythrocytes from chickens was identical to
      apo A-I.

PMID- 8987656
TI  - Isolation and analysis of cinnamic acid 4-hydroxylase homologous genes from a
      hybrid aspen, Populus kitakamiensis.
AB  - Cinnamic acid 4-hydroxylase (CA4H) is the second enzyme involved in
      phenylpropanoid biosynthesis and is a member of the cytochrome P-450 superfamily.
      Three CA4H homologous genes, cyp73A, cyp73b, and cyp73c, and a cDNA clone of
      cyp73a were isolated from a genomic library and a cDNA library of a hybrid aspen;
      Populus kitakamiensis, and were characterized. They might be interrupted by two
      introns each. cyp73a and cyp73b were very similar to each other not only in
      coding regions but also in non-coding regions. Southern blot analysis showed that
      four homologous genes for CA4H constructed a small gene family in the diploid
      genome of P. kitakamiensis. In the promoter regions, there were many common cis
      element-like sequences in phenylpropanoid biosynthesis genes.

PMID- 8987657
TI  - Purification and characterization of extracellular chin deacetylase from
      Colletotrichum lindemuthianum.
AB  - Chitin deacetylase, active in the presence of acetate (96% of the enzymatic
      activity was retained in the presence of 100 mM sodium acetate), was purified to
      electrophoretic homogeneity from a culture filtrate of Colletotrichum
      lindemuthianum (944-fold with a recovery of 4.05%). The enzyme was induced in the
      medium after the eighth day of incubation simultaneously with the blackening of
      the medium. The molecular mass of the enzyme was 31.5 kDa and 33 kDa as judged by
      SDS-PAGE and gel filtration, respectively, suggesting that the enzyme is a single
      polypeptide. The optimum temperature was 60 degrees C and the optimum pH was 11.5
      12.0 when glycol chitin was used as substrate. The enzyme was active toward
      glycol chitin, partially N-deacetylated water soluble chitin, and chitin
      oligomers the degrees of polymerization of which were more than four, but was
      less active with chitin trimer and dimer, and inactive with N-acetylglucosamine.
      The Km and kcat for glycol chitin were 2.55 mM and 27.1 s-1, respectively, and
      those for chitin pentamer were 414 microM and 83.2 s-1, respectively. The
      reaction rates of the enzyme toward glycol chitin and chitin oligomers seemed to
      follow the Michaelis-Menten kinetics.

PMID- 8987658
TI  - Efficient L-serine production from methanol and glycine by resting cells of
      Methylobacterium sp. strain MN43.
AB  - Resting cells of methanol-utilizing microorganisms isolated from soils were
      examined for L-serine production under conditions in which L-serine-degradation
      was suppressed. Strain MN43, a facultative methylotrophic bacterium identified as
      a Methylobacterium sp., was selected for further studies. Under the optimal
      conditions, 65 mg/ml L-serine was produced by this bacterium from 50 mg/ml
      glycine and 104 mg/ml methanol in 5 days, with a molar conversion ratio from
      glycine to L-serine of 93%. This production is the highest so far reported for
      microbes producing L-serine.

PMID- 8987659
TI  - Biodegradation of cellulose acetate by Neisseria sicca.
AB  - Bacteria capable of assimilating cellulose acetate, strains SB and SC, were
      isolated from soil on a medium containing cellulose acetate as a carbon source,
      and identified as Neisseria sicca. Both strains degraded cellulose acetate
      membrane filters (degree of substitution, DS, mixture of 2.8 and 2.0) and
      textiles (DS, 2.34) in a medium containing cellulose acetate (DS, 2.34) or its
      oligomer, but were not able to degrade these materials in a medium containing
      cellobiose octaacetate. Biodegradation of cellulose acetate (DS, 1.81 and 2.34)
      on the basis of biochemical oxygen demand reached 51 and 40% in the culture of N.
      sicca SB and 60 and 45% in the culture of N. sicca SC within 20 days. A decrease
      in the acetyl content of degraded cellulose acetate films and powder was
      confirmed by infrared and nuclear magnetic resonance analyses. After 10-day
      cultivation of N. sicca SB and SC, the number-average molecular weight of
      residual cellulose acetate decreased by 9 and 5%, respectively. Activities of
      enzymes that released acetic acid and produced reducing sugars from cellulose
      acetate were mainly present in the culture supernatant. Reactivity of enzymes for
      cellulose acetate (DS, 1.81) was higher than that for cellulose acetate (DS,
      2.34).

PMID- 8987660
TI  - Molecular cloning and nucleotide sequence of the groEL gene from the alkaliphilic
      Bacillus sp. strain C-125 and reactivation of thermally inactivated alpha
      glucosidase by recombinant GroEL.
AB  - The groEL gene of the alkaliphilic Bacillus sp. strain C-125 was cloned in
      Escherichia coli and sequenced. The groEL gene encoded a polypeptide of 544 amino
      acids and was preceded by the incomplete groES gene, lacking its 5'-end. The
      sequence of the derived amino acids was 87.5% identical to that of B. subtilis,
      85.4% identical to that of B. stearothemophilus, and 60.9% identical to that of
      E. coli. The GroEL protein was expressed in E. coli. Purified GroEL protected
      yeast alpha-glucosidase from irreversible aggregation at a high temperature and
      the addition of Mg-ATP was essential for reactivation of the alpha-glucosidase.
      The addition of E. coli GroES increased recovery of the enzyme activity,
      indicating that C-125 GroEL could function in coordination with E. coli GroES.

PMID- 8987661
TI  - Tastes produced by peptides containing ionic groups and by related compounds.
AB  - The typical tastes imparted by ionic groups are salty-like of sodium chloride and
      umami-like of monosodium glutamate, but the relationship between the taste and
      chemical structure has not previously been elucidated. One of the reason for the
      difficulty in understanding the taste-structure relationship is the presence of
      the ambiguous and unfavorable tastes of neutral salts. We define the strange
      tastes of neutral salts (TNS) collectively in a specific category, and then the
      tastes due to ionic groups. Sour, salty, and umami tastes and TNS were studied
      for different acidic and basic groups and various combinations of both groups to
      elucidate the taste characteristics of the ionic groups. The results reveal that
      the tastes due to ionic groups have common characteristics, being different from
      bitter and sweet tastes.

PMID- 8987662
TI  - Syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives.
AB  - The syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives
      against plant pathogenic fungi and termites were investigated. Dihydro-5,6
      dehydrokawain was isolated by a simple method without chromatography from the
      leaves of Alpinia speciosa K. SCHUM. The white crystalline compound obtained was
      identified as dihydro-5,6-dehydrokawain (1) by instrumental analyses. 4-Hydroxy-6
      (2-phenylethyl)-2H-pyran-2-one (3) was prepared by hydrolyzing dihydro-5,6
      dehydrokawain. Three dihydro-5,6-dehydrokawain derivatives were synthesized by
      reacting 3 with phosphoric agents. Among the synthesized compounds, dimethyl [6
      (2-phenylethyl)-2-oxo-2H-pyran-4-yl]phosphorothionate (4) had the strongest
      antifungal activity of 91% at 100 ppm against Corticium rolfsii.

PMID- 8987663
TI  - Substrate specificity of a novel alcohol resistant metalloproteinase, vimelysin,
      from Vibrio sp. T1800.
AB  - Vimelysin is a novel alcohol resistant metalloproteinase from Vibrio sp. T1800.
      The substrate specificity of vimelysin was studied by using natural and
      furylacryloyl dipeptide substrates. Vimelysin cleaved mainly Pro7-Phe8 bond and
      slightly Tyr4-Ile5 bond in human angiotensin I. Vimelysin also cleaved mainly
      Phe24-Phe25 and Tyr16-Leu17 bonds, and slightly His5-Leu6, His10-Leu11, Ala14
      Leu15, and Gly23-Phe24 bonds in oxidized insulin B-chain. The substrate
      specificity of vimelysin, by using furylacryloyl (Fua) dipeptides were also
      studied. The ratio of kcat/Km for Fua-Gly-Phe-NH2/Fua-Gly-Leu-NH2, Fua-Phe-Leu
      NH2/Fua-Gly-Leu-NH2, and Fua-Phe-Phe-NH2/Fua-Gly-Leu-NH2 were 15.9, 27.8, and
      59.0, respectively. These results indicate that vimelysin easily recognizes
      phenylalanine in P1' positions, which is different from thermolysin.

PMID- 8987664
TI  - Molecular cloning and expression of the pyrimidine nucleoside phosphorylase gene
      from Bacillus stearothermophilus TH 6-2.
AB  - The pyrimidine nucleoside phosphorylase (Py-NPase) of Bacillus stearothermophilus
      TH 6-2 is a dimer of 46-kDa subunits and catalyzes the reversible phosphorolysis
      of uridine and thymidine. The gene encoding this pyrimidine nucleoside
      phosphorylase (pyn gene) has been cloned and sequenced from B. stearothermophilus
      TH 6-2. The pyn gene corresponded to an open reading frame of 1299 nucleotides
      that translates into a putative 433 amino acid protein with a molecular weight of
      46,271. The deduced amino terminal sequence of Py-NPase coincided with that
      previously found for the purified enzyme. The deduced amino acid sequence of Py
      NPase shared significant similarity with those of human and Escherichia coli
      thymidine phosphorylases. The cloned pyn gene was overexpressed in E. coli cells
      to produce an active enzyme in large quantities that accounted for approximately
      20% of the total protein.

PMID- 8987665
TI  - Effects of feeding tryptophan-limiting diets on the conversion ratio of
      tryptophan to niacin in rats.
AB  - We investigated the effects of feeding various types of nicotinic acid-free,
      tryptophan-limiting diets on the conversion ratio of tryptophan to niacin in
      rats. Various tryptophan-limiting diets were made by adding zein, gelatin,
      glycine, threonine, methionine, or glycine + threonine + methionine to a
      nicotinic acid-free, 9% casein diet. When the rats were fed with the tryptophan
      limiting diets, the conversion ratio of tryptophan to niacin was markedly
      decreased. However, the ratio recovered after the addition of tryptophan to the
      tryptophan-limiting diets. These results clearly prove that the conversion was
      lowest when the rats were fed with the tryptophan-limiting diets. Therefore, we
      think that the pellagragenic factor of corn is simply due to a low content of
      tryptophan, but the adverse effect is due to a low conversion ratio of tryptophan
      to niacin.

PMID- 8987666
TI  - In vivo macrophage-stimulation activity of the enzyme-degraded water-soluble
      polysaccharide fraction from a marine alga (Gracilaria verrucosa).
AB  - The water-soluble polysaccharide fraction from Gracilaria verrucosa (GWS) has
      been reported to increase the phagocytic activity of mice [Yoshizawa et al.,
      Nippon Shokuhin Kogyo Gakkaishi, 41, 557-560 (1994)]. In this study, the
      macrophage-stimulation activity of enzyme-degraded GWS (GWS-E) was investigated
      by intraperitoneally and orally administering GWS-E to mice. The intraperitoneal
      administration of GWS-E increased the number of peritoneal exudate cells (PEC),
      and increased the phagocytic activity and oxygen radical-secreting activity
      (spontaneous chemiluminescence) of PEC. This administration could also stimulate
      splenic macrophages (SPM), increasing radical-secreting activity. When GWS-E was
      administered orally, the radical-secreting activity of PEC and SPM increased. In
      this case of oral administration, the activity of SPM increased in a dose
      dependent manner, while that of PEC had an optimum dose. These results indicate
      that GWS-E had macrophage-stimulation activity in vivo and would be suitable as a
      source for a physiologically functional food with protective and
      immunopotentiating activity.

PMID- 8987667
TI  - Nicardipine and nifedipine inhibit fatty acid desaturases in rat liver
      microsomes.
AB  - Nicardipine and nifedipine, Ca channel blockers, inhibited rat liver microsomal
      desaturases, though verapamil, methoxyverapamil, cinnarizine, flunarizine, and
      diltiazem did not. However, nicardipine and nefidipine apparently did not inhibit
      the fungal desaturation in Mortierella alpina 1S-4. Nicardipine inhibited rat
      liver microsomal delta 5 desaturase specifically (50% inhibitory concentration.
      170 microM), and nifedipine inhibited delta 6 desaturase specifically (78
      microM). The inhibition by nicardipine and nifedipine is uncompetitive, the Ki
      values for delta 5 and delta 6 desaturases being 62 and 44 microM, respectively.

PMID- 8987668
TI  - A novel gene that interferes with the phosphotransfer signal transduction
      mediated by the EnvZ osmosensor in Escherichia coli.
AB  - In Escherichia coli, expression of the major outer membrane proteins, OmpC and
      OmpF, is regulated in response to the medium osmolarity and other environmental
      stimuli. A two-component signal transduction system, mediated by EnvZ and OmpR,
      is crucially responsible for this osmotic regulation of the ompC and ompF genes.
      In this study, an E. coli gene was cloned, which interferes with expression of
      both the ompC and ompF genes at the level of transcription, provided that the
      cloned gene was introduced in E. coli cells by a multicopy plasmid. The gene
      product was identified as F107, which was previously characterized as a
      hypothetical protein in E. coli genome databases. F107 containing 107 amino acids
      appears to be highly hydrophobic, and has a sequence similarity to the eukaryotic
      type of cytochrome-c oxidase subunit III. The mechanism by which F107 inhibits
      transcription of ompC and ompF was examined extensively, mainly by using a set of
      envZ and ompR mutants. These results suggested that F107 interferes specifically
      with a function of the EnvZ osmosensory kinase. Possible mechanisms by which F107
      affects the EnvZ function are discussed.

PMID- 8987669
TI  - Cloning of stress tolerance gene in Torulaspora delbrueckii No. 3110.
AB  - A cryptic plasmid (pSRY1) was found in Torulaspora delbrueckii No. 3110. A
      plasmid vector (pSRY21) was constructed by ligating it to pPR1-RIM-C ORF with a
      cycloheximide resistance gene (RIM-C). The transformation efficiency of the
      strain No. 3110 with pSRY21 by the protoplast-PEG method was increased by 3000
      fold by treatment of the protoplasts with polylysine [poly(epsilon-L-lysine)].
      Previously we have reported a mutant No. 3110, T1, which can neither assimilate
      nor accumulate trehalose. The mutant was salt- and temperature-sensitive. We
      cloned a DNA fragment from No. 3110, which, when introduced, complemented these
      mutant characters of T1. These results suggested an important role of metabolism
      of trehalose for the stress tolerance.

PMID- 8987670
TI  - Effects of mepanipyrim on intracellular trafficking: a comparative study on its
      effects on exocytic and endocytic trafficking of proteins, sphingolipids, and
      cholesterol.
AB  - Mepanipyrim, N-(4-methyl-6-prop-1-ynylpyrimidin-2-yl)aniline, diminished the cell
      surface expression of envelope glycoproteins of Newcastle disease and vesicular
      stomatitis viruses at concentrations where their synthesis was not profoundly
      affected. Intoxication by diphtheria toxin and ricin and recycling of transferrin
      were not affected even when cells were treated with mepanipyrim for 2 h before
      the addition of these probes, indicating that mepanipyrim does not act on the
      endocytic and recycling pathways of these proteins. Metabolic conversion of C6
      NBD-ceramide to sphingomyelin and its back-exchange to the medium was also not
      affected, but synthesis and back-exchange of C6-NBD glucosylceramide were greatly
      influenced, and an accumulation of LDL-derived, unesterified cholesterol was
      induced by the drug. These results are discussed relating to the site(s) of
      action of mepanipyrim.

PMID- 8987671
TI  - Antimutagenic effect of methanolic extracts from peanut hulls.
AB  - The antimutagenic effects of methanolic extracts of peanut hulls (MEPH) were
      evaluated by the Ames test. MEPH inhibited the mutagenicity of 4-nitroquinoline-N
      oxide (NQNO), a direct-acting mutagen. MEPH also inhibited the mutagenicity of
      some indirect-acting mutagens and decreased in the order of 2-amino-3-methyl
      imidazo(4,5-f)quinoline (IQ) > aflatoxin B1 (AFB1) > 2-amino-6-methyldipyrido(1,2
      a:3',2'-d)imidazole (Glu-P-1) > 3 amino-1,4-dimethyl-5H-pyridol(4,3-b)indole (Trp
      P-1) > benzo(a)pyrene (B(a)P for S. typhimurium TA98, and IQ > Trp-P-1 > Glu-P-1
      > AFB1 > B(a)P for S. typhimurium TA100.

PMID- 8987672
TI  - Chitinous component of the cell wall of Fusarium oxysporum, its structure deduced
      from chitosanase digestion.
AB  - The cell of Fusarium oxysporum was digested with commercial Bacillus chitosanase.
      The chitosanase produced low molecular weight heterooligosaccharides consisting
      of GlcN and GlcNAc from the cell wall. A main component of the digestion products
      was identified as 2-amino-2-deoxy-beta-D-glucopyranosyl- (1-->4)-2-acetamido-2
      deoxy-D-glucopyranose. The chitosanase appeared to be more effective than
      Streptomyces griseus chitinase for cell wall digestion. Moreover, maltose was
      unexpectedly found in the digestion products, indicating that the cell wall
      contains alpha-1,4-linked glucan chain as a polysaccharide component.

PMID- 8987673
TI  - Effect of natural food colorings on immunoglobulin production in vitro by rat
      spleen lymphocytes.
AB  - Water-soluble (cacao pigment, cochineal pigment, corn pigment, betanin, carthamus
      yellow, and monascus pigment) and water-insoluble (gardenia yellow, laccaic acid,
      bixin, and curcumin) natural colorings inhibited IgE production by rat spleen
      lymphocytes at 10 and microM, respectively. Although many of these colorings only
      inhibited the production of IgG and IgM at high concentrations, the water
      insoluble colorings enhanced IgM production even at 1 microM. These results
      suggest that natural colorings have immunoglobulin production-regulating
      activity.

PMID- 8987675
TI  - Stereoconfiguration of anteiso-fatty biosynthesized from DL-isoleucine in rat
      skin.
AB  - Isoleucine (Ile) is a precursor for the biosynthesis of anteiso-fatty acids in
      rat skin, and among the four possible stereoisomers of Ile, L-Ile, and L-allo-Ile
      were selectively used for biosynthesis of anteiso-fatty acids. This study
      examined the optical rotation of anteiso-fatty acid derived from DL-Ile to
      ascertain its stereoconfiguration. Specific rotation of anteiso-fatty acid
      derived from DL-Ile favorably compared with that derived from L-Ile, suggesting
      the selective biosynthesis of the (S)-enantiomer of anteiso-fatty acid in rat
      skin.

PMID- 8987674
TI  - Gene analysis of trehalose-producing enzymes from hyperthermophilic archaea in
      Sulfolobales.
AB  - The genes encoding new trehalose-producing enzymes from S. acidocaldarius
      ATCC33909 were cloned to analyze the distribution of these genes in Sulfolobales.
      Comparison of the amino acid sequences with S. solfataricus KM1 showed
      approximately 50% similarity. Southern analysis suggest that homologues of the
      trehalose-producing enzyme genes exist widely in sulfolobales and strains in
      Sulfolobales were classified into three kinds of genotypes.

PMID- 8987676
TI  - Identification of low molecular weight probes on perforin- and Fas-based killing
      mediated by cytotoxic T lymphocytes.
AB  - Perforin- and Fas-based killing pathways are two major mechanisms of cytotoxic T
      lymphocytes (CTL)-mediated cytotoxicity. In this paper, we have reported the
      identification of low molecular weight probes on CTL-mediated cytolysis. In
      addition to inhibitors of acidification so far reported, three other groups of
      compounds have been identified to block perforin-based cytolysis by the CD8+ CTL
      clone: (1) an inhibitor of actin polymerization (cytochalasin D), (2) respiratory
      inhibitors (antimycin A and oligomycin A), and (3) protein kinase inhibitors
      (calphostin C, herbimycin A, K252a, and staurosporine). Since Fas-based cytolysis
      by CD4+ CTL clone was inhibitable or rather increased by these agents, only
      vacuolar type H(+)-ATPase inhibitors such as concanamycin A have been shown to be
      highly specific probes to block perforin-based CTL-mediated cytotoxicity.

PMID- 8987677
TI  - Estimation of pH and the number of lytic granules in a CD8+ CTL clone treated
      with an inhibitor of vacuolar type H(+)-ATPase concanamycin A.
AB  - A vacuolar type H(+)-ATPase inhibitor, concanamycin A (CMA), raised the pH and
      induced morphologic changes such as vacuolation in lytic granules in the CD8+
      cytotoxic T lymphocyte clone OE4. Here we measured the pH in lytic granules
      present in OE4 by immunoelectron microscopic observation using (3-(2,4
      dinitroanilino)-3'-amino-N-methyldipropylamine (DAMP) as a pH probe. In control
      OE4, only the peripheral region, but not cores, were heavily stained with DAMP.
      Exposure to 100 nM CMA for 60 min raised the pH in the lytic granules from 5.7 +/
      0.2 to 6.8 +/- 0.2. Furthermore, the number of lytic granules in OE4 was
      estimated under phase contrast microscopy after Wright staining. About 20 lytic
      granules in average were detected in control cells, while CMA induced vacuolation
      and decreased their number by 20 to 30%.

PMID- 8987678
TI  - Effects of beta 1-->4 linked galactooligosaccharides on use of magnesium and
      calcification of the kidney and heart in rats fed excess dietary phosphorous and
      calcium.
AB  - Magnesium deficiency was induced in male Wistar rats by adding an excess of
      phosphorous and calcium to the diet (1.195 g of phosphorous and 1.04 g of
      calcium/100 g of diet). Feeding of these animals with a diet containing beta 1-
      >4 linked galactooligosaccharides (4'-GOS) (5 g of 4'-GOS/100 g of diet)
      increased the apparent magnesium absorption ratios and the concentrations of
      magnesium in the serum and femur, and reduced accumulation of calcium in the
      kidney and heart. We speculate that the use of magnesium increased by feeding 4'
      GOS to a limited extent prevented the lower magnesium status and the severity of
      calcification of the kidney and heart caused by excess dietary phosphorous and
      calcium.

PMID- 8987679
TI  - Analysis of catalytic action of transglutaminase induced in human promyelocytic
      leukemia (HL-60) and human hepatoblastoma (HepG2) cells.
AB  - Transglutaminase is a calcium-dependent enzyme that catalyzes an amine
      incorporation and a cross-linking of proteins. Intracellular transglutaminase is
      induced when human promyelocytic leukemia HL-60 cells are treated with retinoic
      acid and human hepatoblastoma HepG2 cells, with interleukin-6. To find whether
      the intracellular reaction catalyzed by transglutaminase increased when the
      enzyme is induced in these cells, the transglutaminase-catalyzed incorporation of
      14C-labeled methylamine into cellular proteins was measured. The incorporation
      level of the labeled methylamine into proteins of HL-60 and HepG2 cells did not
      increase after the transglutaminase had been induced. The presence of the calcium
      ionophore A23187 did not affect these results. These findings suggested that even
      after the enzyme induction the catalytic action of intracellular transglutaminase
      is maintained at a constant level in these cells by unknown regulatory
      mechanism(s).

PMID- 8987680
TI  - Fractionation of proteins with modified membranes.
AB  - The fractionation of two proteins, either positively charged (Lysozyme) or
      negatively charged (bovine serum albumin, BSA) was investigated by varying the
      ionic strength with unmodified or positively charged inorganic ultrafiltration
      membranes. Chemical modification was obtained by coating of polyvinylimidazole
      which amine groups reacted further with bisepoxiranes in order to have both
      partly quaternized amine group and pH stable network on membrane surface. The
      retention of the single protein decreases, with ionic strength when electrostatic
      interactions between the free protein in the bulk and the adsorbed protein onto
      the membrane are occurring. An increase of single protein retention with modified
      membranes appears at high ionic strength due to hydrophobic interactions between
      proteins and polymer coating. For protein mixtures, at low ionic strength
      (0.015), observed selectivities are more than 10 whatever the membrane used; both
      membrane fouling and protein-protein interactions occur in the protein mixture.
      At intermediate (0.25 M) and high (1 M) ionic strengths, the observed selectivity
      with modified membranes remains stable (about 6) whereas selectively with
      unmodified membranes decreases and is close to size selectivity. Hence the
      fractionation of proteins with modified membranes remains satisfactory in the
      entire range of ionic strengths due to ionic and salt promoted interactions
      between protein and membranes.

PMID- 8987681
TI  - Partitioning of beta-mannanase and alpha-galactosidase from Aspergillus niger in
      Ucon/Reppal aqueous two-phase systems and using temperature-induced phase
      separation.
AB  - Enzyme partitioning and recovery with a new aqueous two-phase system based on
      commercially available hydroxypropyl starch Reppal PES 200 and the thermo
      separating polymer Ucon 50-HB-5100 was studied. Ucon is an ethylene oxide
      propylene oxide random copolymer. A culture supernatant of Aspergillus niger
      containing extracellular beta-mannanase and alpha-galactosidase was partitioned
      in two steps. The primary aqueous two-phase system contained Ucon and Reppal as
      phase forming polymers. The effect on enzyme partitioning of salt composition,
      salt concentration, pH and polymer concentration was studied with the aim of
      obtaining optimal partitioning of target enzymes to the phase containing the
      thermoseparating Ucon polymer. The partitioning of the enzymes could be strongly
      influenced by addition of the hydrophobic triethyl ammonium ion and the
      chaotropic perchlorate ion. Also the effect on cationic surfactant, cetyl
      trimethyl ammonium bromide, on enzyme partitioning was studied. In the second
      step, temperature induced phase separation was carried out on the isolated Ucon
      phase. A water phase and a concentrated aqueous Ucon phase were formed. The
      enzymes were obtained in the water phase almost free of polymer.

PMID- 8987682
TI  - An investigation into the possible use of hydrocyclones for the removal of yeast
      from beer.
AB  - This investigation has focused on the importance of hydrocyclone design and
      running conditions for the removal of yeast from suspensions. Experiments have
      been carried out using both a model system of yeast grown in suspension cultures
      and rough beer. It appeared that the most important factor was the design of the
      hydrocyclone with a positive correlation between higher residence times and
      acceleration with the efficiency of separation. The other factor that affected
      the separation efficiency was the concentration of the yeast suspension and a new
      phenomenon of a lower efficiency of hydrocyclones at very low feed concentrations
      has been observed. The separation efficiency was also affected by temperature
      with lower temperatures giving poorer separations.

PMID- 8987683
TI  - Purification of murine IgG1 on group specific affinity sorbents.
AB  - Murine IgG1 a CD4-antibody, was produced from the cell line MAX 16 H 5. DEAE
      Sepharose CL-6B and group specific sorbents based on different ligands, such as
      protein A-Sepharose, AvidChrom, Thiophilic Resin (T-Resin) Fractogel EMD TA 650S,
      Sepharose 4B-immobilized metal chelate and histidine sorbents, were compared in
      terms of their suitability for the large-scale purification of this IgG.
      Evaluation criteria were selectivity for IgG1 protein capacity and recovery,
      stability under cleaning-in-place (CIP) conditions and the rate of IgG1
      adsorption. Both thiophilic gels performed best under these conditions, with
      Fractogel EMD TA 650S demonstrating slightly higher contamination with other
      proteins compared to the T-Resin based on 6% beaded Agarose. Higher purities were
      obtained with these gels compared to conventional purification techniques
      employing a combination of ion exchange and hydrophobic interaction
      chromatography. Favorable adsorption kinetics were found on DEAE-Sepharose with
      the effective diffusivity in the pores of the sorbent being five-times
      accelerated compared to the diffusion coefficient of IgG1 in solution. Multilayer
      adsorption of the IgG1 was experienced from adsorption isotherms on DEAE
      Sepharose and Fractogel EMD TA 650S. This was linked to an early breakthrough of
      this protein during frontal chromatography. Co-purification of pyrogens between
      two-(Thiophilic Resin) and five-times (DEAE-Sepharose) of the original level was
      significant with all sorbents except protein A-Sepharose and AvidChrom. Thus an
      additional chromatographic step is required in case of pyrogen contamination of
      the cell culture homogenate.

PMID- 8987684
TI  - Centrifugal recovery and dissolution of recombinant Gly-IGF-II inclusion-bodies:
      the impact of feedrate and re-centrifugation on protein yield.
AB  - The impact of centrifuge feedrate and multiple centrifuge passes on protein yield
      following recombinant Gly-Insulin-like Growth Factor II (Gly-IGF-II) inclusion
      body dissolution has been investigated. Altering centrifuge feedrate did not
      significantly improve the overall protein yield following dissolution. Improved
      centrifuge recovery at a low feedrate was offset by poorer inclusion body paste
      purity. This reduced purity resulted in a significant loss of protein during
      inclusion-body dissolution due to proteolysis. Multiple centrifuge passes
      improved the inclusion-body paste purity. This resulted in a net improvement in
      the overall protein yield following dissolution. This work demonstrates that a
      strong interaction exists between centrifuge performance and inclusion-body
      dissolution for protease-sensitive products such as Gly-IGF-II.

PMID- 8987685
TI  - Polymer-shielded dye-ligand chromatography of lactate dehydrogenase from porcine
      muscle in an expanded bed system.
AB  - Dye-affinity chromatography is a widely used technique in protein purification.
      It has recently been shown that the efficiency of the chromatography process can
      be significantly improved by pretreatment of the affinity matrix with certain
      water soluble polymers such as poly(vinyl pyrrolidone). This technique termed as
      polymer-shielded, dye-affinity chromatography has been successfully used in
      packed bed mode at a lab scale for the purification of a number of enzymes. The
      present work deals with the application of polymer-shielded dye-affinity
      chromatography in an expanded bed system of Streamline-Cibacron Blue 3GA for the
      isolation of lactate dehydrogenase from a crude porcine muscle extract. The
      elution conditions were optimised to obtain an efficient process. A higher
      recovery of the target enzyme (78%) was obtained from the polymer shielded column
      as compared to the unshielded column (17%), after low ionic strength elution. The
      purification factor obtained after chromatography on the polymer shielded column
      was higher (4.1) than that from unshielded column (1.8).

PMID- 8987686
TI  - Variation in sessile microflora during biofilm formation on AISI-304 stainless
      steel coupons.
AB  - Coupons of stainless steel type AISI-304 were exposed to the industrial cooling
      system of a petrochemical plant fed by seawater from the Guanabara Bay, Rio de
      Janeiro, Brazil, in order to study the in situ formation of biofilms. Bacteria,
      microalgae and fungi were detected on the coupons as soon as 48 h after exposure.
      Their respective numbers were determined at times 48, 96 and 192 h and over the
      following 8 weeks. Aerobic, anaerobic and sulfate-reducing bacteria were
      quantified according to the technique of the most probable number, and fungi by
      the pour plate technique. The number of microorganisms present in the forming
      biofilm varied over the experimental period, reaching maximal levels of 14 x
      10(11) cells cm-2, 30 x 10(13) cells cm-2, 38 x 10(11) cells cm-2 and 63 x 10(5)
      cells cm-2, respectively, for aerobic bacteria, anaerobic bacteria, sulfate
      reducing bacteria and fungi, and the dynamics of this variation depended on the
      group of microorganisms. Bacillus sp, Escherichia coli, Serratia sp and
      Pseudomonas putrefaciens were identified among the aerobic bacteria isolated.
      Additionally, microalgae and bacteria of the genus Gallionella were also
      detected. Nonetheless, no evidence of corrosion was found on the stainless steel
      type AISI-304 coupons over the experimental period.

PMID- 8987687
TI  - Fermentation of xylose and rice straw hydrolysate to ethanol by Candida shehatae
      NCL-3501.
AB  - Candida shehatae NCL-3501 utilized glucose and xylose efficiently in batch
      cultures. The specific rate of ethanol production was higher with mixtures of
      glucose and xylose (0.64-0.83 g g-1 cells d-1) compared to that with individual
      sugars (0.38-0.58 g g-1 cells d-1). Although the optimum temperature for growth
      was 30 degrees C, this strain grew and produced appreciable levels of ethanol at
      45 degrees C. A stable ethanol yield (0.40-0.43 g g-1 substrate utilized) was
      obtained between 10 g L-1 and 80 g L-1 of initial xylose concentration.
      Conversion efficiency was further improved by immobilization of the cells in
      calcium alginate beads. Free or immobilized cells of C. shehatae NCL-3501
      efficiently utilized sugars present in rice straw hemicellulose hydrolysate,
      prepared by two different methods, with 48 h. Ethanol yields of 0.45 g g-1 and
      0.5 g g-1 from autohydrolysate, and 0.37 g g-1 from acid hydrolysate were
      produced by free and immobilized cells, respectively.

PMID- 8987688
TI  - Expression of mouse metallothionein in the cyanobacterium Synechococcus PCC7942.
AB  - A cDNA encoding mouse metallothionein was cloned into the shuttle vector pUc303,
      creating a translational fusion with the bacterial chloramphenicol
      acetyltransferase gene. The resulting fusion protein has been expressed in the
      cyanobacterium Synechococcus PCC7942. Cyanobacterial transformants expressed
      mouse metallothionein-specific mRNA species as detected by RNA slot blots. In
      addition, the transformants expressed a unique cadmium ion-binding protein
      corresponding to the predicted size of the mouse metallothionein fusion protein.
      Expression of this fusion protein conferred a two- to five-fold increase in
      cadmium ion tolerance and accumulation on Synechococcus PCC7942.

PMID- 8987690
TI  - Effect of hydromechanical stress on cellular antigens of Bordetella pertussis.
AB  - Cells of Bordetella pertussis grown in a bioreactor under stirring conditions
      were studied to investigate the effect of shear stress on cellular-bound
      filamentous haemagglutinin (FHA). FHA attached to the bacterial surface, unlike
      extracellular FHA, was not affected at the shear levels tested. Moreover, no
      other cellular immunogen involved in the whole-cell protective activity seemed to
      be affected by hydromechanical forces.

PMID- 8987689
TI  - A direct comparison of approaches for increasing carbon flow to aromatic
      biosynthesis in Escherichia coli.
AB  - Different approaches to increasing carbon commitment to aromatic amino acid
      biosynthesis were compared in isogenic strains of Escherichia coli. In a strain
      having a wild-type PEP:glucose phosphotransferase (PTS) system, inactivation of
      the genes encoding pyruvate kinase (pykA and pykF) resulted in a 3.4 fold
      increase in carbon flow to aromatic biosynthesis. In a strain already having
      increased carbon flow to aromatics by virtue of overexpression of the tktA gene
      (encoding transketolase), the pykA and/or pykf mutations had no effect. A PTS-
      glucose+ mutant showed a 1.6-fold increase in carbon flow to aromatics compared
      to the PTS+ control strain. In the PTS- glucose+ host background, overexpression
      of tktA caused a further 3.7-fold increase in carbon flow, while inactivation of
      pykA and pykF caused a 5.8-fold increase. When all of the variables tested (PTS
      glucose+, pykA, pykF, and overexpressed tktA) were combined in a single strain, a
      19.9-fold increase in carbon commitment to aromatic biosynthesis was achieved.

PMID- 8987691
TI  - Antimicrobial effects of hydrophilic extracts of Pelargonium species
      (Geraniaceae).
AB  - Methanolic extracts of representative species and cultivars of Pelargonium
      (Geraniaceae) were assessed for activity against 25 different species of bacteria
      and Aspergillus niger. All samples were active against at least 18 bacterial
      species and some were active against all 25 species, although there was very poor
      antifungal action. Antioxidant action was very pronounced, and this together with
      the strong antibacterial activity indicates that there is a potential usage in
      the food or other industry for Pelargonium extracts.

PMID- 8987692
TI  - Studies of Clostridium cellulolyticum ATCC 35319 under dialysis and co-culture
      conditions.
AB  - The degradation of cellulose by Clostridium cellulolyticum has been studied in
      several ways: (1) in batch fermentation in 50-ml sealed-cap flasks, referred to
      as the control; (2) in batch fermentation with pH at 7.2; (3) fermentation in
      dialysis which permits elimination of all the products of metabolism; (4)
      fermentation in dialysis with a constant bubbling of nitrogen; (5) in co-culture
      with Clostridium A22 in batch with and without pH regulation and with dialysis.
      H2, CO2, acetate, ethanol and lactate were the major end-products of cellobiose
      and cellulose fermentation. Compared to batch culture, growth of Cl.
      cellulolyticum on cellobiose increased by a factor of 10 in dialysed culture. The
      end products from the dialysed culture were detected in a small range compared to
      the concentration for the batch culture. Related to the biomass, CMCase
      activities were of the same level, showing a direct relation between the biomass
      formation and the cellulase production. The percentage of cellulose degradation
      (50%) by Cl. cellulolyticum was greater when dialysis of end products with a
      constant bubbling of nitrogen took place during the course of fermentation (6 d)
      in comparison with cultures in 50-ml sealed-cap flasks (23%), in a fermentor
      (36%) or using dialysis without N2 bubbling (40%). The presence of two micro
      organisms produced no further enzyme activities and hence the percentage of
      cellulose degradation was quite similar in mono- and co-culture. No synergistic
      action was found between two cellulolytic strains.

PMID- 8987693
TI  - Associated mycoflora of rye bread.
AB  - Penicillium roqueforti (27%), P. corylophilum (20%) and Eurotium species (15%)
      made up the important mycoflora associated with rye bread on 3425 identified
      fungi isolates. These fungi were dominant as spoilers of packaged rye bread in
      almost every month of a 4 year investigation. Penicillium decumbens (3%),
      Paecilomyces variotti (8%) and Aspergillus flavus (5%) were found more rarely,
      but were the major species found over periods of a few months. Penicillium
      commune (5%), P. solitum (4%), A. niger (4%) and Mucor species (2%) were a
      constant, but small, part of the total mycoflora of rye bread. Identification of
      the fungi in the production environment in a rye bread factory showed the
      locality of potential contamination sources. Elimination of the contamination
      sources by improved cleaning and disinfection procedures quickly resulted in a
      significant reduction in the frequency of mould growth in the packaged rye bread.

PMID- 8987694
TI  - 16S rDNA analysis of Butyrivibrio fibrisolvens: phylogenetic position and
      relation to butyrate-producing anaerobic bacteria from the rumen of white-tailed
      deer.
AB  - Complete 16S rDNA sequences of six strains of Butyrivibrio fibrisolvens,
      including the type strain (ATCC 19171), were determined. The type strain was
      found to have less than 89% sequence similarity to the other isolates that were
      examined. The five plasmid-bearing strains formed a closely related cluster and
      three of these strains (OB156, OB157 and OB192) were very highly related (> 99%),
      indicating that they are isolates of the same genomic species. The phylogenetic
      position of Butyrivibrio was found to be within the subphylum Clostridium, of
      Gram-positive bacteria. The closest relatives to the type strain were Eubacterium
      cellulosolvens and Cl. xylanolyticum and the closest relatives to the separately
      clustered strains were Roseburia ceciola, Lachnospira pectinoschiza and
      Eubacterium rectale.

PMID- 8987695
TI  - An opportunity to distinguish species of Saccharomyces sensu stricto by
      electrophoretic separation of the larger chromosomes.
AB  - Intact chromosomal DNA of the type strains of Saccharomyces sensu stricto species
      and some of their synonyms and 38 Hungarian wine and 14 brewing yeast strains
      were separated by rotating field gel electrophoresis (RFE). The applied
      electrophoretic conditions enabled us to distinguish strains of S. bayanus, S.
      pastorianus and S. cerevisiae from each other, for strains of the three species
      showed clear differences in their electrophoretic patterns at heavy chromosomes
      (> 1300 kb).

PMID- 8987696
TI  - Rapid detection and isolation of DNA-binding compounds from Streptomyces
      xanthochromogenes.
AB  - The culture medium of Streptomyces xanthochromogenes JH903 was found to show
      selective activity against DNA-repair-deficient Escherichia coli CM871 strain. In
      this report we describe a simple method to locate and isolate DNA binding
      compounds from the fermentation broth. The method is based on the retention of
      DNA-reacting compounds in cellulose complexed with DNA, and purification of these
      compounds with thin-layer chromatography. Screening of microbial metabolites from
      chloroform extracts of fermentation media resulted in detection of five genotoxic
      fractions.

PMID- 8987697
TI  - Identification of Arcobacter isolates by PCR.
AB  - A polymerase chain reaction (PCR) assay was developed for the identification of
      the three species of Arcobacter which have been recovered from clinically ill or
      healthy humans and/or livestock, namely Arcobacter butzleri, Arcobacter skirrowii
      and Arcobacter cryaerophilus. The assay utilizes primers targeted to the genes
      encoding 16S rRNA of Arcobacter spp. The assay reduces the amount of time
      required to positively identify strains of Arcobacter.

PMID- 8987698
TI  - Characterization of novel non-toxic Bacillus thuringiensis isolates from Korea.
AB  - Four Bacillus Thuringiensis isolates from soil samples produced parasporal
      inclusions which were non-toxic to insects. The isolates were named B.
      thuringiensis NTB-1, NTB-2, NTB-3 and NTB-4. The parasporal inclusions were shown
      to be ovoid by phase contrast and scanning electron microscopy. The serotypes of
      the four isolates were determined by agglutination using 33 antisera; NTB-1 and
      NTB-4 seemed to be subsp. israelensis, and NTB-2 seemed to be subsp.
      pondicheriensis. NTB-3 did not react with the 33 antisera. However, comparison of
      parasporal protein and plasmid DNA patterns of the four isolates with those of 15
      known non-toxic B. thuringiensis strains demonstrated that the four isolates are
      novel.

PMID- 8987699
TI  - Galacto-oligosaccharide production from lactose by Sirobasidium magnum CBS6803.
AB  - Galacto-oligosaccharide (Gal-OS) was produced from lactose by a yeast,
      Sirobasidium magnum CBS6803. With toluene-treated resting cells, 136 mg ml-1 of
      Gal-OS was produced from 360 mg ml-1 of lactose at 50 degrees C for 42 h. Then,
      the yield of Gal-OS was increased by a culture method in which cell growth
      followed the enzymatic reaction: 224 mg ml-1 of Gal-OS was produced at 30 degrees
      C for 60 h. Finally, combination of the toluene-treated resting cells and glucose
      oxidase plus catalase was applied to improve productivity by the removal of a by
      product, glucose, which inhibits the Gal-OS production, from the reaction
      mixture. In this case, 242 mg ml-1 of Gal-OS was produced at 50 degrees C for 42
      h without cell growth. The structure of the major product was identified as 4'
      galactosyl-lactose.

PMID- 8987700
TI  - Diversity of bacterial capabilities in utilizing alkylated benzenes and other
      aromatic compounds.
AB  - Seventeen aerobic bacterial strains known to degrade one or more aromatic
      compounds were tested for their ability to utilize benzene, seven different
      methylated benzenes or other aromatic compounds as their sole source of carbon.
      The results are discussed with respect to the possibility of finding strains
      which degrade one or more of these compounds by the applied method of screening,
      and to their taxonomic status.

PMID- 8987701
TI  - Detection of maltose fermentation genes in the baking yeast strains of
      Saccharomyces cerevisiae.
AB  - The presence of any one of the five unlinked MAL loci (MAL1, MAL2, MAL3, MAL4 and
      MAL6) confers the ability to ferment maltose on the yeast Saccharomyces
      cerevisiae. Each locus is composed of three genes encoding maltose permease,
      alpha-glucosidase and MAL activator. Chromosomal DNA of seven representative
      baking strains has been separated by pulse-field gel electrophoresis and probed
      with three genes in MAL6 locus. The DNA bands to which all of the three MAL
      derived probes simultaneously hybridized were chromosome VII carrying MAL1 in all
      of the strains tested, chromosome XI carrying MAL4 in six strains, chromosome III
      carrying MAL2 in three strains and chromosomes II and VIII carrying MAL3 and
      MAL6, respectively, in the one strain. The number of MAL loci in baking strains
      was comparable to those of brewing strains.

PMID- 8987702
TI  - Induction of the PhoE porin by NaCl as the basis for salt-induced acid
      sensitivity in Escherichia coli.
AB  - Organisms grown in low salt broth (LSB) are acid resistant but become sensitive
      on growth for 30-60 min with 300 mmol l-1 added NaCl. Salt-induced acid
      sensitivity only occurs in relA+ strains and sensitization is abolished by
      glucose, this catabolite repression effect being reversed by cAMP. The finding
      that sensitization did not occur in a phoE strain but did occur in a phoE+
      derivative of it suggested that the response might result from PhoE induction,
      since PhoE acts as the major outer membrane (OM) proton pore under most
      conditions. In agreement with this, low-salt broth (LSB)-grown cells of a
      chromosomally lac- strain carrying pJP102 (phoE-lacZ) produced low levels of beta
      galactosidase but growth with added NaCl led to rapid and appreciable induction.
      Also, a phoA mutant carrying a phoE-phoA fusion produced little alkaline
      phosphatase after growth in LSB but much more in LSB with added NaCl. Increased
      beta-galactosidase synthesis (in phoE-lacZ strains) in the presence of NaCl was
      abolished by glucose, this effect being reversible by cAMP, and there was more
      NaCl-induced synthesis of this enzyme in relA+ strains. Accordingly, it appears
      that addition of NaCl to LSB leads to acid sensitivity because it induces
      synthesis of the OM proton pore PhoE.

PMID- 8987704
TI  - Bacteriophages: a model system for human viruses.

PMID- 8987703
TI  - 11-Hydroxy-4-methyl-2,4,6-dodecatrienoic acid from fermentations of a Mucor
      species.
AB  - 11-Hydroxy-4-methyl-2,4,6-dodecatrienoic acid was isolated from fermentations of
      the Mucor species, strain KL 94-92 aq. The compound exhibits cytotoxic activity
      and the structural elucidation, as well as the biological properties of the new
      compound, are described.

PMID- 8987705
TI  - Production of chitinase and beta-N-acetylglucosaminidase by intestinal bacteria
      of Pinnipedian animals.
AB  - The chitinase- and beta-N-acetylglucosaminidase(GlcNAcase)-producing ability of
      intestinal bacteria from Pinnipedian animals was determined using fluorogenic 4
      methylumbelliferone glycosides of N-acetylglucosamine oligosaccharides.
      Intestinal microflora of a single Cape fur seal, three California sea lions and
      three South American sea lions were characterized by a predominance of isolates
      of the Bacteroidaceae and Enterobacteriaceae families and the genus Clostridium.
      Of the 711 isolates tested 26.0, 10.0 and 8.7% could hydrolyse 4-MU(GlcNAc)1, 4
      MU(GlcNAc)2 and 4-MU(GlcNAc)3, respectively. This result suggests that beta
      GlcNAcase producers occur at a higher density than do chitinase producers.
      Moreover, beta-GlcNAcase, and to a lesser degree, chitinase seem to be
      efficiently produced by facultative anaerobes in the Cape fur seal and the
      California sea lion, and by both facultative and obligated anaerobes in the South
      American sea lion. To our knowledge, this is the first paper to report that
      isolates of the family Bacteroidaceae and the genus Streptococcus produce
      chitinase and/or beta-GlcNAcase.

PMID- 8987706
TI  - Identification of flagellar (H) antigenic subfactors in Bacillus thuringiensis H
      serotypes 10, 18 and 24 isolated in Japan.
AB  - A total of 95 Bacillus thuringiensis strains isolated from Japan and belonging to
      H serotypes 10, 18 and 24, were examined for their H antigenic subfactors. Of 84
      H serotype 10 isolates, 83 were identified as the H serotype 10a: 10b (serovar
      darmstadiensis) and only one isolate was assigned to the H serotype 10a: 10c
      (serovar londrina). Among five isolates belonging to the H serotype 18, three
      were allocated to the H serotype 18a: 18b (serovar kumamotoensis), while two
      isolates did not react to antisera against the two known H antigenic subfactors,
      18b and 18c. All of the six H serotype 24 isolates were assigned to the H
      serotype 24a: 24b (serovar neoleonensis).

PMID- 8987708
TI  - Detection of Hsp60 (Gro-EL)-like proteins in Vibrio parahaemolyticus and Vibrio
      species by western immunoblotting analysis.
AB  - Detection of heat shock proteins in Vibrio parahaemolyticus was investigated by
      SDS-PAGE and Western immunoblotting procedure using an anti-Hsp 60 antibody.
      Results indicate that V. parahaemolyticus elicited at least one Hsp 60 (GroEL)
      like protein with apparent molecular weight of about 58,000 (58 kDa) when
      submitted to a heat shift from 30 to 42 degrees C. Kanagawa phenomenon-positive
      and -negative strains of V. parahaemolyticus responded the same way. Six other
      Vibrio species also showed an increased synthesis of GroEL-like (58 kDa) protein
      after heat shock, while synthesis of 58 kDa protein of V. alginolyticus was at a
      similar level before and after heat shock. Vibrio nereis showed an increased
      synthesis of a 60 kDa GroEL-like protein.

PMID- 8987707
TI  - Alanine germination receptors of Bacillus subtilis.
AB  - The alanine-stimulated spore germination responses of Bacillus subtilis 168 have
      been dissected by combining physiological and genetical approaches. From the
      analyses the authors infer that there are three classes of alanine response. Two
      of the responses are mediated via the GerA proteins, with and without germinal
      adjuncts, the third is mediated via the GerB proteins and obligately requires
      adjuncts.

PMID- 8987709
TI  - Aerobic degradation of 2-sulphobenzoic acid by Pseudomonas strain SB(W).
AB  - A 2-sulphobenzoic acid-degrading bacterium, Pseudomonas sp. strain SB(W), was
      isolated from creosote-contaminated soil. It used this compound as its sole
      carbon, sulphur and energy source, and gave a nearly stoichiometric release of
      sulphate from 2-sulphobenzoic acid. It did not grow on 3- to 4- sulphobenzoic
      acids. Isolated SB(W) produced two transient metabolites. The first to appear,
      and the more abundant metabolite, was identified as 2,3-dihydroxybenzoic acid.
      The second metabolite was identified as salicylic acid. Both of these compounds
      served as growth substrates for the isolates.

PMID- 8987710
TI  - Antigenicity and N-terminal amino acid sequence of a 35 kDa porin-like protein of
      Listonella (Vibrio) anguillarum: comparison among different serotypes and other
      bacterial species.
AB  - Listonella (Vibrio) anguillarum, an important fish pathogen, is divided into 10
      serotypes according to O-antigens present on the outer membrane. However, the
      biochemical and immunological properties of porin proteins have not been
      reported. In this study, the antigenicity and N-terminal amino acid sequence of
      the 35 kDa porin-like-major outer membrane protein (Omp35La) were compared among
      different serotypes of L. anguillarum as well as other bacteria. In Western
      blotting analysis, antisera against Omp35La from strains of J-O-1, -2 and -3
      serotypes could detect Omp35La, but not other proteins, in most L. anguillarum
      strains and isolated of the genera Vibrio and Photobacterium. This antigenicity
      of Omp35La is unrelated to the serotype and is conserved in related organisms. An
      N-terminal sequence showed identification with OmpF and OmpC of Escherichia coli
      and Salmonella typhimurium. However, this similarity was lower when compared to
      other human pathogens. Thus it was concluded that Omp35La does not contribute to
      the serotypes of L. anguillarum, although the N-terminal structure is well
      conserved among different serotypes.

PMID- 8987711
TI  - Random-amplified polymorphic DNA (RAPD) analysis shows intraspecies differences
      among Xanthomonas albilineans strains.
AB  - Five strains of Xanthomonas albilineans, causal agent of leaf scald disease in
      sugarcane from various geographical regions, were compared using random
      amplification of polymorphic DNA (RAPD) to determine whether they could be
      differentiated at the DNA level. CsCl-purified genomic DNA from these strains
      were amplified by the polymerase chain reaction (PCR) using arbitrary 10-mer
      primers according to standard RAPD conditions and the amplification product
      profiles analysed by conventional agarose gel electrophoresis. Although most RAPD
      markers were common to all five strains, unique profiles for each strain were
      discernible using four 10-mer arbitrary primers individually. Reproducible DNA
      fingerprints indicate that RAPD analysis can be used to identify and
      differentiate the X. albilineans strains. This technique has the potential for
      use in monitoring the appearance of foreign strains of X. albilineans in various
      geographical regions and could be used for the construction of phylogenetic
      trees.

PMID- 8987712
TI  - Characterization of Cryptococcus neoformans by random DNA amplification.
AB  - Random amplified polymorphic DNA (RAPD) was optimized and used to distinguish
      between the varieties and serotypes of Cryptococcus neoformans. The RAPD
      technique distinguished between serotypes A, D or AD within C. neoformans var.
      neoformans, and revealed further differentiation within each serotype. Four RAPD
      profiles were clearly recognizable within C. neoformans var. gattii, although its
      two serotypes, B and C, were only differentiated with one primer combination out
      of seven.

PMID- 8987713
TI  - Isolation of Escherichia coli O157 from raw meat products.
AB  - This study has evaluated an enrichment and four subculture procedures for
      detection of Escherichia coli O157 in raw meat products. The combination of
      enrichment in modified tryptone broth incubated at 42 degrees C for 6 h, followed
      by immunomagnetic separation and subculture on to cefixime, tellurite sorbitol
      MacConkey agar was the most sensitive and selective procedure. Traditional
      subculture using 10 microliters and 100 microliters inocula and culture of
      centrifuged deposits were less satisfactory. A most probable number method was
      used to enumerate E. coli O157 in naturally contaminated samples associated with
      human cases. The results indicated that the samples contained < 0.3 to 2300 cfu g
      1 of E. coli O157 which confirms that the infective dose for this organism is
      low.

PMID- 8987714
TI  - Serological identification of infection by verocytotoxin-producing Escherichia
      coli.
AB  - One hundred sera from patients with haemolytic ureamic syndrome were screened for
      antibodies to the lipopolysaccharide (LPS) of Escherichia coli serogroup O5, O26,
      O115, O128, O145 and O153, and Shigella dysenteriae 1. Three sera contained
      antibodies to the LPS of E. coli belonging to serogroup O5.

PMID- 8987715
TI  - An in situ method for determining bacterial survival on food preparation surfaces
      using a redox dye.
AB  - A simple method is described for the direct enumeration of viable bacteria dried
      on test surfaces. Inoculated surfaces were overlayed with agar and after
      incubation nitroblue tetrazolium solution (pale yellow) was used to stain
      colonies (purple) at the agar-test surface interface. Stained colonies could be
      readily detected and counted even against the opaque background of ceramic tile
      or stainless steel or when present within opaque films of milk or serum. Recovery
      of bacterial by this method was approximately fivefold greater than using a
      conventional swabbing procedure. The method was used to demonstrate the marked
      effect of the composition of the suspension fluid, in which bacteria were dried,
      and the length of surface exposure upon bacterial survival.

PMID- 8987716
TI  - Irreversible paraben inhibition of glycolysis by Streptococcus mutans GS-5.
AB  - Parabens were found to inhibit irreversibly glycolysis by the cariogenic dental
      plaque bacterium Streptococcus mutans GS-5 and to decrease the capacity of the
      bacterium to lower the pH in dense cell suspensions containing excess glucose.
      The hierarchy of effectiveness was butyl > propyl > ethyl > methyl paraben.
      Results of studies of the nature of glycolytic inhibition by butyl paraben
      indicated that it could act at millimolar concentrations as an irreversible
      inhibitor of the phosphotransferase system for sugar uptake and was lethal for
      the bacterium at these same levels. Butyl paraben acted also as a reversible
      inhibitor of the F-ATPase of the organism. Overall, it appeared that the lethal
      actions of parabens can be interpreted at least in part as due to irreversible
      damage to key enzymes, such as those of the phosphotransferase system.

PMID- 8987717
TI  - Cross-infection of chicks by airborne transmission of Salmonella enteritidis PT4.
AB  - Airborne cross-infection by Salmonella enteritidis PT4 strains was demonstrated
      between sets of orally infected 1-d-old chicks and identical uninfected control
      chicks. Low numbers of Salm. enteritidis were detected in the air of the rooms
      housing the chicks. Sentinel mice within the rooms did not become infected. This
      study demonstrates that low levels of airborne Salm. enteritidis are a potential
      source of cross-infection in poultry houses.

PMID- 8987718
TI  - Specific primers for detection of Alicyclobacillus acidoterrestris by RT-PCR.
AB  - The reverse transcription-polymerase chain reaction (RT-PCR), after a short
      enrichment culture, was used to detect Alicyclobacillus acidoterrestris in acidic
      beverages. Two specific primers were selected from the region of V2 and V4 on 16S
      rRNA gene. With this primer set, 294-bp fragments from A. acidoterrestris could
      be amplified. The detection limit of the RT-PCR with the FHLP filters was about
      10-1 fg of pure total RNA per reaction. Juice samples inoculated with 10(4) cfu
      of A. acidoterrestris per ml were RT-PCR positive without enrichment. However,
      after 15 h of enrichment, the samples inoculated with 2-3 cfu ml-1 were positive.
      This RT-PCR culture assay would enable rapid and specific detection of strains of
      A. acidoterrestris in acidic beverages.

PMID- 8987719
TI  - A new species of Neisseria from the dental plaque of the domestic cow, Neisseria
      dentiae sp. nov.
AB  - A new species of the genus Neisseria is proposed, Neisseria dentiae sp. nov. The
      organism is found in dental plaque of domestic cows. It resembles N. animalis, N.
      canis and N. iguanae phenotypically but is distinguished from the first two by
      being positive for acidification of gluconate, D-glucose and usually D-fructose,
      and from the third by lack of predominant tetrad arrangement, lack of distinct
      alpha-haemolysis and by growing on nutrient agar and usually acidifying D
      fructose. It is suggested that it may have significance for dental microbiology
      because members of the genus rapidly utilize oxygen and this may contribute to
      the anaerobic microenvironment found in dental plaque.

PMID- 8987720
TI  - Detection of Campylobacter jejuni and Camp. coli in chicken faecal samples by
      PCR.
AB  - PCR primers were selected from the flagellin gene sequences flaA and flaB of
      Campylobacter coli to amplify DNA from Camp. jejuni and Camp. coli. When the PCR
      products were analysed by hybridization to an internal probe immobilized in
      microtitre wells, positive reactions were observed only for strains of Camp.
      jejuni and Camp. coli. The assay was used to analyse 31 chicken faecal samples.
      Full correspondence was found between the PCR assay conducted on the enriched
      cultures and the standard culture method. When analysing the transport medium
      prior to enrichment, the PCR assay detected nine of 11 culture positive samples.

PMID- 8987721
TI  - Mathematical description of the growth of Lactobacillus sake and Lactobacillus
      pentosus under conditions prevailing in fermented sausages.
AB  - The growth behaviour of Lactobacillus sake and Lactobacillus pentosus was
      determined in a model system stimulating the conditions of fermenting sausages.
      Minor effects on the growth were observed by varying the concentrations of
      glucose, peptone, manganese and sodium nitrite. Temperature and sodium chloride
      concentration were found to have most effect on the growth. The measured data
      were used for a mathematical model describing the growth response of L. sake and
      L. pentosus sufficiently well to estimate the behaviour of the investigated
      strains. In all combinations relevant to sausage fermentation L. sake proved to
      be more competitive. It exhibited a shorter lag phase, higher maximal growth rate
      and higher final cell yield than L. pentosus.

PMID- 8987722
TI  - Native and heterologous protein secretion by Streptomyces lividans.
AB  - The secretion of the heterologous parathion phosphotriesterase in S. lividans
      using the Streptomyces beta-galactosidase signal sequence was further
      characterised using a pulse/chase system. Unsecreted cell-associated protein in
      both the precursor and signal-cleaved forms was observed when the protein was
      expressed from both low- and high-copy vectors. Fractionation of the cells
      followed by immunoprecipitation with phosphotriesterase antibody suggests that
      the precursor is membrane-bound while the signal cleaved form is present in the
      soluble fraction. Preliminary data on the processing of alpha-amylase, a native
      streptomyces protein, showed much more rapid processing and secretion, but
      nevertheless still revealed cell-associated, signal-cleaved protein.

PMID- 8987723
TI  - Properties of an intracellular beta-glucosidase purified from the cellobiose
      fermenting yeast Candida wickerhamii.
AB  - An intracellular beta-glucosidase was isolated from the cellobiose-fermenting
      yeast, Candida wickerhamii. Production of the enzyme was stimulated under aerobic
      growth, with the highest level of production in a medium containing cellobiose as
      a carbohydrate source. The molecular mass of the purified protein was
      approximately 94 KDa. It appeared to exist as a dimeric structure with a native
      molecular mass of about 180 KDa. The optimal pH ranged from 6.0 to 6.5 with p
      nitrophenyl beta-D-glucopyranoside (NpGlc) as a substrate. The optimal
      temperature for short-term (15-min) assays was 35 degrees C, while temperature
      stability analysis revealed that the enzyme was labile at temperatures of 28
      degrees C and above. Using NpGlc as a substrate, the enzyme was estimated to have
      a Km of 0.28 mM and a Vmax of 525 mumol product min-1 mg protein-1. Similar to
      the extracellular beta-glucosidase produced by C. wickerhamii, this enzyme
      resisted end-product inhibition by glucose, retaining 58% of its activity at 100
      mM glucose. The activity of the enzyme was highest against aryl beta-1,4
      glucosides. However, p-nitrophenyl xylopyranoside, lactose, cellobiose, and
      trehalose also served as substrates for the purified protein. Activity of the
      enzyme was stimulated by long-chain n-alkanols and inhibited by ethanol, 2
      propanol, and 2-butanol. The amino acid sequence, obtained by Edman degradation
      analysis, suggests that this beta-glucosidase is related to the family-3 glycosyl
      hydrolases.

PMID- 8987724
TI  - Optimization of the benzoate-inducible benzoate p-hydroxylase cytochrome P450
      enzyme system in Aspergillus niger.
AB  - Introduction in the fungus Aspergillus niger of multiple copies of the A. niger
      bphA gene, encoding the cytochrome P450 enzyme benzoate p-hydroxylase, did not
      result in increased activities of this enzyme [Gorcom RFM van, et al. Mol Gen
      Genet (1990) 223: 192-197] probably because of low expression levels of the gene
      encoding the second component of the microsomal cytochrome P450 enzyme system,
      cytochrome P450 reductase. For improvement of this and other cytochrome-P450
      dependent reactions, A. niger strains were constructed in which the copy number
      of the A. niger cprA gene (encoding cytochrome-P450 reductase) or the copy
      numbers of both cprA and the cytochrome-P450-encoding gene were increased.
      Expression of both genes was controlled by their own transcription control
      regions. Benzoate p-hydroxylase activity of different transformants was
      determined in microsomal fractions using a newly developed indirect in vitro
      assay. In transformants containing multiple copies of both genes, benzoate p
      hydroxylase activity was significantly higher than in the wild-type strain or in
      transformants in which the copy number of only one of the genes was increased.
      These results clearly indicate the importance of co-expression of cytochrome-P450
      reductase for achieving maximal cytochrome P450 activities in cytochrome-P450
      overproducing filamentous fungi.

PMID- 8987725
TI  - Overexpression of binding protein and disruption of the PMR1 gene synergistically
      stimulate secretion of bovine prochymosin but not plant thaumatin in yeast.
AB  - When the heterologous proteins thaumatin and bovine prochymosin are produced in
      yeast cells as a fusion with the yeast invertase secretory signal peptide, less
      than 2% of the product is secreted in a biologically active form into the medium.
      The remainder accumulates intracellularly in a misfolded conformation. We
      investigated whether this poor secretion can be improved by overexpression of
      binding protein (BiP) one of the major chaperones in eukaryotic cells. Indeed, a
      tenfold increase in the level of binding protein, as a result of the introduction
      of extra copies of the kar2 gene into yeast cells containing a single, integrated
      copy of the invertase/prochymosin fusion gene, caused more than a 20-fold
      increase in the amount of extracellular prochymosin. By additional disruption of
      the PMR1 gene of these cells we were able to obtain secretion of virtually all of
      the prochymosin produced. Export of thaumatin, on the other hand, was not
      significantly stimulated by binding protein overexpression.

PMID- 8987726
TI  - A new glucose oxidase from Aspergillus niger: characterization and regulation
      studies of enzyme and gene.
AB  - A new glucose oxidase from Aspergillus niger was isolated and characterized. The
      enzyme showed different kinetic and stability characteristics when compared to a
      commercially available batch of A. niger glucose oxidase. The gene encoding the
      new glucose oxidase was isolated and DNA sequence analysis of the coding region
      showed 80% identity to the sequence of a glucose oxidase gene previously
      published. However, the similarity of the non-coding sequences up- and downstream
      of the open reading frame was much less, showing only 66% and 50% identity
      respectively. Despite the low degree of similarity between the promotor region of
      the new gene and the previously published one, the new glucose oxidase was
      likewise induced by calcium carbonate. In addition, we showed that this induction
      occurred on the transcriptional level. Observations concerning the effect of
      gluconolactone and the levels of glucose-6 phosphate isomerase upon calcium
      carbonate induction suggested that the enhancement of glucose oxidase
      biosynthesis by calcium carbonate was accompanied by a metabolic shift from
      glycolysis to the pentose phosphate pathway.

PMID- 8987727
TI  - Metabolism of ricinoleate by Neurospora crassa.
AB  - Neurospora crassa is a potential expression system for evaluating fatty-acid
      modifying genes from plants producing uncommon fatty acids. One such gene encodes
      the hydroxylase that converts oleate to ricinoleate, a fatty acid with important
      industrial uses. To develop this expression system, it is critical to evaluate
      the metabolism and physiological effects of the expected novel fatty acid(s). We
      therefore examined effects of ricinoleate on lipid biosynthesis and growth of N.
      crassa. Ricinoleate inhibited growth and reduced levels of phospholipids and 2
      hydroxy fatty acids in glycolipids, but led to increased lipid accumulation on a
      mass basis. To evaluate incorporation and metabolism of ricinoleate, we followed
      the fate 14 microM-3mM [1-14C]ricinoleate. The fate of the [14C]ricinoleate was
      concentration-dependent. At higher concentrations, ricinoleate was principally
      incorporated into triacylglycerols. At lower concentrations, ricinoleate was
      principally metabolized to other compounds. Thus, N. crassa transformants
      expressing the hydroxylase gene can be detected if the level of hydroxylase
      expression allows both growth and ricinoleate accumulation.

PMID- 8987728
TI  - The cytosolic pathway of L-malic acid synthesis in Saccharomyces cerevisiae: the
      role of fumarase.
AB  - Saccharomyces cerevisiae accumulates L-malic acid but not only minute amounts of
      fumaric acid. A 13C-nuclear magnetic resonance study following the label from
      glucose to L-malic acid indicates that the L-malic acid is synthesized from
      pyruvic acid via oxaloacetic acid. From this, and from previously published
      studies, we conclude that a cytosolic reductive pathway leading from pyruvic acid
      via oxaloacetic acid to L-malic acid is responsible for the L-malic acid
      production in yeast. The non-production of fumaric acid can be explained by the
      conclusion that, in the cell, cytosolic fumarase catalyzes the conversion of
      fumaric acid to L-malic but not the reverse. This conclusion is based on the
      following findings. (a) The cytosolic enzyme exhibits a 17-fold higher affinity
      towards fumaric acid than towards L-malic acid; the Km for L-malic acid is very
      high indicating that L-malic acid is not an in vivo substrate of the enzyme. (b)
      Overexpression of cytosolic fumarase does not cause accumulation of fumaric acid
      (but rather more L-malic acid). (c) According to 13C NMR studies there is no
      interconversion of cytosolic L-malic and fumaric acids.

PMID- 8987729
TI  - Evaluation of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose, a
      new fluorescent derivative of glucose, for viability assessment of yeast Candida
      albicans.
AB  - A new fluorescent derivative of D-glucose, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino]-2-deoxy-D-glucose (2-NBDG), which had been previously developed for the
      analysis of glucose uptake activity by living cells, was investigated to evaluate
      its applicability for assaying the viability of yeast Candida albicans.
      Lineweaver-Burk plots showed to uptake of 2-NBDG to be competitively inhibited by
      D-glucose and not by L-glucose, which suggested the involvement of the glucose
      transporting system of C. albicans in the uptake of 2-NBDG. A good correlation
      was obtained between the yeast viability, determined by the plate-count method,
      and the 2-NBDG uptake activity of yeast cells (correlation constant: r = 0.97).
      This is expected to lead to the development of a new fluorescent probe for the
      determination of yeast cell viability.

PMID- 8987730
TI  - Effect of vitamins on the aerobic degradation of 2-chlorophenol, 4-chlorophenol,
      and 4-chlorobiphenyl.
AB  - The effect of vitamins on the aerobic degradation and dechlorination of 2
      chlorophenol and 4-chlorophenol by Pseudomonas pickettii, strain LD1, and 4
      chlorobiphenyl by Pseudomonas sp. strain CPE1 was determined. These
      microorganisms are capable of using the target compounds as the sole carbon and
      energy source, but do not need vitamins to metabolize them. The addition to the
      culture medium of a vitamin solution containing biotin, folic acid, pyridoxine
      hydrochloride, riboflavin, thiamine hydrochloride, niacin, pantothenic acid,
      cyanocobalamin, p-aminobenzoic acid, and thioctic acid (total final
      concentration: < or = 600 ppb) resulted in a 7%-16% increase in the amount of
      target compounds degraded over the incubation period required for the
      concentration of the compound in the cultures to drop to approximately zero. A
      corresponding increase in the amount of chloride ion produced was also detected
      during the same period, indicating active (and often stoichiometric)
      dechlorination of the target compounds.

PMID- 8987731
TI  - Cellular and regional distribution of the glutamate transporter GLAST in the CNS
      of rats: nonradioactive in situ hybridization and comparative
      immunocytochemistry.
AB  - Oligonucleotide and cRNA probes were used for nonradioactive in situ
      hybridizations carried out to identify the neural cell types expressing the
      glutamate transporter GLAST mRNA in the rat CNS. Additionally, the regional
      distribution of GLAST mRNA-expressing cells was studied, and the results were
      complemented by immunocytochemical investigations using an antibody against a
      synthetic GLAST peptide. The findings documented that GLAST is expressed by
      Bergmann glia and by astrocytes throughout the CNS. The glial localization of
      GLAST mRNA was verified unequivocally by double-labeling with an astrocytic
      marker protein. Additionally, GLAST mRNA reactivity and GLAST immunoreactivity
      were found in ependymal cells. In other neural cell types of the CNS, GLAST
      expression was not detectable. A high level of astrocytic immunolabeling was
      observed in the entire gray matter of the brain, with variations in intensity in
      different regions. Those brain areas that are known to possess high glutamatergic
      activity and astrocytic glutamate metabolism stained intensely for both GLAST
      mRNA and GLAST protein. The latter observation suggests that the GLAST glutamate
      transporter participates in the regulation of extracellular glutamate
      concentrations, especially in brain areas receiving an intense glutamatergic
      innervation.

PMID- 8987732
TI  - mu-Opioid receptors modulate NMDA receptor-mediated responses in nucleus
      accumbens neurons.
AB  - The nucleus accumbens (NAcc) may play a major role in opiate dependence, and
      central NMDA receptors are reported to influence opiate tolerance and dependence.
      Therefore, we investigated the effects of the selective mu-opioid receptor
      agonist [D-Ala2-N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) on membrane properties of
      rat NAcc neurons and on events mediated by NMDA and non-NMDA glutamate receptors,
      using intracellular recording in a brain slice preparation. Most NAcc neurons
      showed a marked inward rectification (correlated with Cs+- and Ba2+-sensitive
      inward relaxations) when hyperpolarized, as well as a slowly depolarizing ramp
      with positive current pulses. Superfusion of DAMGO did not alter membrane
      potential, input resistance, or the inward relaxations. In the presence of 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX) used to block non-NMDA glutamate
      receptors and bicuculline to block GABAA receptors, EPSPs evoked by local
      stimulation displayed characteristics of an NMDA component: (1) long duration,
      (2) voltage sensitivity, and (3) blockade by the NMDA receptor antagonist DL-2
      amino-5-phosphonovaleric acid (D-APV). DAMGO (0.1-1 muM) significantly decreased
      both NMDA- and non-NMDA-EPSP amplitudes with reversal of this effect by naloxone
      and the mu-selective antagonist [Cys2-Tyr3-Orn5-Pen7]-somatostatinamide (CTOP).
      To assess a postsynaptic action of DAMGO, we superfused slices with tetrodotoxin
      and evoked inward currents by local application of glutamate agonists.
      Surprisingly, 0.1-1 microM DAMGO markedly enhanced the NMDA currents (with
      reversal by CTOP) but reduced the non-NMDA currents. At higher concentrations (5
      microM), DAMGO reduced NMDA currents, but this effect was enhanced, not blocked,
      by CTOP. These results indicate a complex DAMGO modulation of the NMDA component
      of glutamatergic synaptic transmission in NAcc: mu receptor activation decreases
      NMDA-EPSP amplitudes presynaptically yet increases NMDA currents
      postsynaptically. These new data may provide a cellular mechanism for the
      previously reported role of NMDA receptors in opiate tolerance and dependence.

PMID- 8987733
TI  - Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody.
AB  - The neurological mouse mutant strain reeler displays abnormal laminar
      organization of several brain structures as a consequence of a defect in cell
      migration during neurodevelopment. This phenotype is a result of the disruption
      of reelin, a gene encoding a protein that has several structural characteristics
      of extracellular matrix proteins. To understand the molecular basis of the action
      of Reelin on neuronal migration, we constructed a full-length reelin clone and
      used it to direct Reelin expression. Here, we demonstrate that Reelin is a
      secreted glycoprotein and that a highly charged C-terminal region is essential
      for secretion. In addition, we demonstrate that an amino acid sequence present in
      the N-terminal region of Reelin contains an epitope that is recognized by the CR
      50 monoclonal antibody. CR-50 was raised against an antigen expressed in normal
      mouse brain that is absent in reeler mice. The interaction of CR-50 with its
      epitope leads to the disruption of neural cell aggregation in vitro. Here, we
      used CR-50 to precipitate Reelin from reticulocyte extracts programmed with
      reelin mRNA, from cells transfected with reelin clones, and from cerebellar
      explants. The reelin gene product seems to function as an instructive signal in
      the regulation of neuronal migration.

PMID- 8987734
TI  - A novel subunit for shal K+ channels radically alters activation and
      inactivation.
AB  - Shal (Kv4) potassium channel genes encode classical subthreshold A-currents, and
      their regulation may be a key factor in determining neuronal firing frequency.
      The inactivation rate of Shal channels is increased by a presently unidentified
      class of proteins in both Drosophila and mammals. We have cloned a novel Shal
      channel subunit (jShalgamma1) from the jellyfish Polyorchis penicillatus that
      alters Shal currents from both invertebrates and vertebrates. When co-expressed
      with the conserved jellyfish Shal homolog jShal1, jShalgamma1 dramatically
      changes both the rate of inactivation and voltage range of activation and steady
      state inactivation. jShalgamma1 provides fast inactivation by a classic N-type
      mechanism, which is independent of its effects on voltage dependence. jShalgamma1
      forms functional channels only as a heteromultimer, and jShalgamma1 + jShal1
      heteromultimers are functional only in a 2:2 subunit stoichiometry.

PMID- 8987735
TI  - Protein kinase C activation regulates human serotonin transporters in HEK-293
      cells via altered cell surface expression.
AB  - Antidepressant- and cocaine-sensitive serotonin (5-hydroxytryptamine, 5-HT)
      transporters (SERTs) dictate clearance of extracellular 5-HT after release. To
      explore protein kinase C-mediated SERT regulation, we generated a stable human
      SERT (hSERT)-expressing cell line (293-hSERT) and evaluated modulation of 5-HT
      activity via studies of 5-HT flux, hSERT-mediated currents under voltage clamp,
      and surface distribution of SERT protein. 293-hSERT cells exhibit saturable, high
      affinity, and antidepressant-sensitive 5-HT uptake as well as hSERT-dependent
      whole-cell currents. In these cells, the protein kinase C activator beta-PMA
      caused a time-dependent reduction in 5-HT uptake capacity (Vmax) after acute
      application and a reduction in SERT-mediated currents. Effects of beta-PMA were
      mimicked by the phorbol ester beta-PDBu, were not observed with the inactive
      alpha-isomers, and could be blocked by treatment of cells with the protein kinase
      C inhibitor staurosporine. Biotinylation/immunoblot analyses showed that activity
      reductions are paralleled by a staurosporine-sensitive loss of surface SERT
      protein. These data indicate that altered surface abundance, rather than reduced
      catalytic transport efficiency, mediates acute PKC-dependent modulation of 5-HT
      uptake.

PMID- 8987736
TI  - Single-channel properties of recombinant AMPA receptors depend on RNA editing,
      splice variation, and subunit composition.
AB  - Non-NMDA glutamate receptor subunits of the AMPA-preferring subfamily combine to
      form ion channels with heterogeneous functional properties. We have investigated
      the effects of RNA editing at the Q/R site, splice variation of the "flip/flop"
      cassette, and multimeric subunit assembly on the single-channel conductance and
      kinetic properties of the recombinant AMPA receptors formed from GluR2 and GluR4
      expressed in HEK 293 cells. We found that AMPA receptor single-channel
      conductance was dependent on the Q/R site editing state of the subunits
      comprising the channel. Calcium-permeable (unedited) channels had resolvable
      single-channel events with main conductance states of 7-8 pS, whereas fully
      edited GluR2 channels had very low conductances of approximately 300 fS
      (estimated from noise analysis). Additionally, the flip splice variant of GluR4
      conferred agonist-dependent conductance properties reminiscent of those found for
      a subset of AMPA receptors in cultured cerebellar granule cells. These results
      provide a description of the single-channel properties of certain recombinant
      AMPA receptors and suggest that the single-channel conductance may be determined
      by the expression of edited GluR2 subunits in neurons.

PMID- 8987737
TI  - Peptidergic modulation of intrathalamic circuit activity in vitro: actions of
      cholecystokinin.
AB  - Cholecystokinin (CCK)-mediated actions on intrathalamic rhythmic activities were
      examined in an in vitro rat thalamic slice preparation. Single electrical stimuli
      in the thalamic reticular nucleus (nRt) evoked rhythmic activity (1-15 sec
      duration) in nRt and the adjacent ventrobasal nucleus (VB). Low CCK
      concentrations (20-50 nM) suppressed rhythmic oscillations in 43% of experiments
      but prolonged such activities in the remaining slices. Higher CCK concentrations
      (100-400 nM) had a predominantly antioscillatory effect. Suppression of
      oscillations was associated with a relatively large membrane depolarization of
      nRt neurons that changed their firing mode from phasic (burst) to tonic (single
      spike) output. This decreased burst discharge of nRt neurons during CCK
      application reduced inhibitory drive onto VB neurons from multiple peaked
      inhibitory postsynaptic currents (IPSCs) to single peaked inhibitory events. We
      hypothesize that suppression of inhibitory drive onto VB neurons decreases their
      probability of burst output, which, together with a reduction of nRt burst
      output, dampens the oscillatory activity. Low CCK concentrations, which produced
      little or no depolarization of nRt neurons, did not alter the firing mode of the
      nRt neurons. However, the probability of burst output from nRt neurons in
      response to subthreshold stimuli was increased in low CCK concentrations,
      presumably leading to an increase in the number of nRt neurons participating in
      the rhythmic activity. Our findings suggest that the neuropeptide CCK, by
      altering the firing characteristics of nRt neurons, has powerful modulatory
      effects on intrathalamic rhythms; the ultimate action was dependent on CCK
      concentration and resting state of these cells.

PMID- 8987738
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar
      granule neurons from apoptosis by activating the mitogen-activated protein kinase
      (MAP kinase) pathway.
AB  - Pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38) are
      neuropeptides of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon
      family. PACAP receptors are expressed in different brain regions, including
      cerebellum. We used primary culture of rat cerebellar granule neurons to study
      the effect of PACAP-38 on apoptosis induced by potassium deprivation. We
      demonstrated that PACAP-38 increased survival of cerebellar neurons in a dose
      dependent manner by decreasing the extent of apoptosis estimated by DNA
      fragmentation. PACAP-38 induced activation of the extracellular signal-regulated
      kinase (ERK)-type of mitogen-activated protein (MAP) kinase through a cAMP
      dependent pathway. PD98059, an inhibitor of MEK (MAP kinase kinase), completely
      abolished the antiapoptotic effect of PACAP-38, suggesting that MAP kinase
      pathway activation is necessary for PACAP-38 action.

PMID- 8987739
TI  - The role of synaptic and voltage-gated currents in the control of Purkinje cell
      spiking: a modeling study.
AB  - We have used a realistic computer model to examine interactions between synaptic
      and intrinsic voltage-gated currents during somatic spiking in cerebellar
      Purkinje cells. We have shown previously that this model generates realistic in
      vivo patterns of somatic spiking in the presence of continuous background
      excitatory and inhibitory input (). In the present study, we analyzed the flow of
      synaptic and intrinsic currents across the dendritic membrane and the interaction
      between the soma and dendrite underlying this spiking behavior. This analysis
      revealed that: (1) dendritic inward current flow was dominated by a
      noninactivating P-type calcium current, resulting in a continuous level of
      depolarization; (2) the mean level of this depolarization was controlled by the
      mean rate of excitatory and inhibitory synaptic input; (3) the synaptic control
      involved a voltage-clamping mechanism exerted by changes of synaptic driving
      force at different membrane potentials; (4) the resulting total current through
      excitatory and inhibitory synapses was near-zero, with a small outward bias
      opposing the P-type calcium current; (5) overall, the dendrite acted as a
      variable current sink with respect to the soma, slowing down intrinsic inward
      currents in the soma; (6) the somato-dendritic current showed important phasic
      changes during each spike cycle; and (7) the precise timing of somatic spikes was
      the result of complex interactions between somatic and dendritic currents that
      did not directly reflect the timing of synaptic input. These modeling results
      suggest that Purkinje cells act quite differently from simple summation devices,
      as has been assumed previously in most models of cerebellar function. Specific
      physiologically testable predictions are discussed.

PMID- 8987740
TI  - A direct comparison of the single-channel properties of synaptic and
      extrasynaptic NMDA receptors.
AB  - The assumption that synaptic and extrasynaptic glutamate receptors are similar
      underpins many studies that have sought to relate the behavior of channels in
      excised patches to the macroscopic properties of the EPSC. We have examined this
      issue for NMDA receptors in cerebellar granule cells, the small size of which
      allows the opening of individual synaptic NMDA channels to be resolved directly.
      We have used whole-cell patch-clamp recordings to determine the conductance and
      open time of NMDA channels activated during the EPSC and used cell-attached and
      outside-out recordings to examine NMDA receptors in somatic membrane. Conductance
      and open time of synaptic channels were indistinguishable from those of
      extrasynaptic channels in cell-attached patches. However, the channel conductance
      in outside-out patches was 20% lower than in cell-attached recordings. This
      change was partially reduced by dantrolene and phalloidin, suggesting that it may
      involve depolymerization of actin following Ca2+ release from intracellular
      stores. Our results demonstrate that synaptic and extrasynaptic NMDA receptors
      have similar microscopic properties. However, NMDA channel conductance is reduced
      following the formation of an outside-out patch.

PMID- 8987741
TI  - Prostaglandin F2alpha is required for NMDA receptor-mediated induction of c-fos
      mRNA in dentate gyrus neurons.
AB  - Activation of NMDA receptors has been linked to a diversity of lasting
      physiological and pathological changes in the mammalian nervous system. The
      cellular and molecular mechanisms underlying permanent modifications of nervous
      system structure and function after brief episodes of neuronal activity are
      unknown. Immediate-early genes (IEGs) have been implicated in the conversion of
      short-term stimuli to long-term changes in cellular phenotype by regulation of
      gene expression. The intracellular signaling pathways coupling activation of
      receptors at the cell surface with induction of IEGs in the nucleus are
      incompletely understood. NMDA produces a striking increase in the IEG c-fos in
      dentate gyrus (DG) neurons in vitro; this induction is dependent, in part, on the
      arachidonic acid cascade. Here we show that NMDA receptor activation triggers the
      synthesis of the prostaglandins PGF2alpha and PGE2, but not PGD2, in rat cerebral
      cortical neurons in vitro. We further demonstrate that PGF2alpha, but not PGE2 or
      PGD2, is necessary but not sufficient for NMDA induction of c-fos mRNA in DG
      neurons. These findings provide insight into the molecular events coupling
      activation of the NMDA receptor with regulation of the IEG c-fos and identify the
      diffusable messenger PGF2alpha as obligatory for NMDA receptor-mediated
      transcription of a nuclear IEG.

PMID- 8987742
TI  - Developmental expression of platelet-derived growth factor alpha-receptor in
      neurons and glial cells of the mouse CNS.
AB  - The synthesis of platelet-derived growth factor-alpha receptor (PDGF-alphaR) is
      commonly attributed to oligodendrocyte progenitors during late embryonic and
      postnatal development. However, we recently demonstrated that mature neurons
      could also synthesize PDGF-alphaR, emphasizing a larger role for this receptor
      than previously described. In the present study, to analyze the pattern of PDGF
      alphaR expression during postnatal development of the mouse CNS, we used in situ
      hybridization and immunohistochemistry on brain and spinal cord tissue sections.
      We found that, in addition to immature cells of the oligodendrocyte lineage,
      neurons of various CNS regions express PDGF-alphaR transcripts and protein as
      early as postnatal day 1 (P1). Whereas neuronal expression was maintained at all
      ages, the oligodendroglial expression strongly decreased after P21. In the adult,
      PDGF-alphaR was detected in very few oligodendrocyte progenitors scattered in the
      cerebral cortex or in white matter tracts, thus suggesting the presence of PDGF
      alphaR on O-2Aadult progenitors. In the mature CNS, PDGF-alphaR transcripts and
      protein were mainly localized in neurons of numerous structures, such as the
      olfactory bulb, cerebral cortex, hippocampus, and brainstem nuclei and in motor
      neurons of the ventral horn of the spinal cord. The differential expression of
      PDGF-alphaR in oligodendroglia and neurons argues in favor of several roles of
      PDGF during development.

PMID- 8987743
TI  - Trafficking of cell-surface beta-amyloid precursor protein: evidence that a
      sorting intermediate participates in synaptic vesicle recycling.
AB  - We recently demonstrated that the Alzheimer's beta-amyloid precursor protein
      (APP) is internalized from the axonal cell surface. In this study, we use
      biochemical and cell biological methods to characterize endocytotic compartments
      that participate in trafficking of APP in central neurons. APP is present in
      presynaptic clathrin-coated vesicles purified from bovine brain, together with
      the recycling synaptic vesicle integral membrane proteins synaptophysin,
      synaptotagmin, and SV2. In contrast, APP is largely excluded from synaptic
      vesicles purified from rat brain. In primary cerebellar macroneurons, cell
      surface APP is internalized with recycling synaptic vesicle integral membrane
      proteins but is subsequently sorted away from synaptic vesicles and transported
      retrogradely to the neuronal soma. Internalized APP partially co-localizes with
      rab5a-containing compartments in axons and with V-ATPase-containing compartments
      in both axons and neuronal soma. These results provide direct biochemical
      evidence that an obligate sorting compartment participates in the regeneration of
      synaptic vesicles during exo/endocytotic recycling at nerve terminals but do not
      preclude concurrent "kiss-and-run" recycling. Moreover, APP is now, to our
      knowledge, the first demonstrated example of an axonal cell-surface protein that
      is internalized with recycling synaptic vesicle membrane proteins but is
      subsequently sorted away from synaptic vesicles.

PMID- 8987744
TI  - Essential role for dlg in synaptic clustering of Shaker K+ channels in vivo.
AB  - The assemblage of specific ion channels and receptors at synaptic sites is
      crucial for signaling between pre- and postsynaptic cells. However, the
      mechanisms by which proteins are targeted to and clustered at synapses are poorly
      understood. Here we show that the product of the Drosophila discs-large gene,
      DLG, is colocalized with Shaker K+ channels, which are clustered at glutamatergic
      synapses at the larval neuromuscular junction. In heterologous cells, DLG can
      cluster Shaker-type K+ channels, and, in the yeast two-hybrid system, the DLG
      PDZ1-2 domains bind directly to the C-terminal tail of Shaker proteins. We also
      demonstrate that DLG-Shaker interactions are required in vivo for Shaker
      clustering at the neuromuscular junction. Synaptic clustering of Shaker channels
      is abolished not only by mutations in dlg but also by a mutation in Shaker that
      deletes its C-terminal DLG binding motif. Analyses of various dlg mutant alleles
      suggest that channel clustering and synaptic targeting functions depend on
      distinct DLG domains. These studies demonstrate for the first time that DLG plays
      an important role in synaptic organization in vivo that correlates with its
      ability to bind directly to specific membrane proteins of the synapse.

PMID- 8987745
TI  - Low-threshold Ca2+ currents in dendritic recordings from Purkinje cells in rat
      cerebellar slice cultures.
AB  - Voltage-dependent Ca2+ conductances were investigated in Purkinje cells in rat
      cerebellar slice cultures using the whole-cell and cell-attached configurations
      of the patch-clamp technique. In the presence of 0.5 mM Ca2+ in the extracellular
      solution, the inward current activated with a threshold of -55 +/- 1.5 mV and
      reached a maximal amplitude of 2.3 +/- 0.4 nA at -31 +/- 2 mV. Decay kinetics
      revealed three distinct components: a fast (24.6 +/- 2 msec time constant), a
      slow (304 +/- 46 msec time constant), and a nondecaying component. Rundown of the
      slow and sustained components of the current, or application of antagonists for
      the P/Q-type Ca2+ channels, allowed isolation of the fast-inactivating Ca2+
      current, which had a threshold for activation of -60 mV and reached a maximal
      amplitude of 0.7 nA at a membrane potential of -33 mV. Both activation and steady
      state inactivation of this fast-inactivating Ca2+ current were described with
      Boltzmann equations, with half-activation and inactivation at -51 mV and -86 mV,
      respectively. This Ca2+ current was nifedipine-insensitive, but its amplitude was
      reduced reversibly by bath-application of NiCl2 and amiloride, thus allowing its
      identification as a T-type Ca2+ current. Channels with a conductance of 7 pS
      giving rise to a fast T-type ensemble current (insensitive to omega-Aga-IVA) were
      localized with a high density on the dendritic membrane. Channel activity
      responsible for the ensemble current sensitive to omega-Aga-IVA was detected with
      10 mM Ba2+ as the charge carrier. These channels were distributed with a high
      density on dendritic membranes and in rare cases were also seen in somatic
      membrane patches.

PMID- 8987746
TI  - Specialized membrane domains for water transport in glial cells: high-resolution
      immunogold cytochemistry of aquaporin-4 in rat brain.
AB  - Membrane water transport is critically involved in brain volume homeostasis and
      in the pathogenesis of brain edema. The cDNA encoding aquaporin-4 (AQP4) water
      channel protein was recently isolated from rat brain. We used immunocytochemistry
      and high-resolution immunogold electron microscopy to identify the cells and
      membrane domains that mediate water flux through AQP4. The AQP4 protein is
      abundant in glial cells bordering the subarachnoidal space, ventricles, and blood
      vessels. AQP4 is also abundant in osmosensory areas, including the supraoptic
      nucleus and subfornical organ. Immunogold analysis demonstrated that AQP4 is
      restricted to glial membranes and to subpopulations of ependymal cells. AQP4 is
      particularly strongly expressed in glial membranes that are in direct contact
      with capillaries and pia. The highly polarized AQP4 expression indicates that
      these cells are equipped with specific membrane domains that are specialized for
      water transport, thereby mediating the flow of water between glial cells and the
      cavities filled with CSF and the intravascular space.

PMID- 8987747
TI  - Conservation of topology, but not conformation, of the proteolipid proteins of
      the myelin sheath.
AB  - The proteolipid protein gene products DM-20 and PLP are adhesive intrinsic
      membrane proteins that make up >/=50% of the protein in myelin and serve to
      stabilize compact myelin sheaths at the extracellular surfaces of apposed
      membrane lamellae. To identify which domains of DM-20 and PLP are positioned
      topologically in the extracellular space to participate in adhesion, we
      engineered N-glycosylation consensus sites into the hydrophilic segments and
      determined the extent of glycosylation. In addition, we assessed the presence of
      two translocation stop-transfer signals and, finally, mapped the extracellular
      and cytoplasmic dispositions of four antibody epitopes. We find that the
      topologies of DM-20 and PLP are identical, with both proteins possessing four
      transmembrane domains and N and C termini exposed to the cytoplasm. Consistent
      with this notion, DM-20 and PLP contain within their N- and C-terminal halves
      independent stop-transfer signals for insertion into the bilayer of the rough
      endoplasmic reticulum during de novo synthesis. Surprisingly, the conformation
      (as opposed to topology) of DM-20 and PLP may differ, which has been inferred
      from the divergent effects that many missense mutations have on the intracellular
      trafficking of these two isoforms. The 35 amino acid cytoplasmic peptide in PLP,
      which distinguishes this protein from DM-20, imparts a sensitivity to mutations
      in extracellular domains. This peptide may normally function during
      myelinogenesis to detect conformational changes originating across the bilayer
      from extracellular PLP interactions in trans and trigger intracellular events
      such as membrane compaction in the cytoplasmic compartment.

PMID- 8987748
TI  - Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1
      dendrites and dendritic spines of the immature and mature rat.
AB  - Recent studies have shown high levels of calcium in activated dendritic spines,
      where the smooth endoplasmic reticulum (SER) is likely to be important for
      regulating calcium. Here, the dimensions and organization of the SER in
      hippocampal spines and dendrites were measured through serial electron microscopy
      and three-dimensional analysis. SER of some form was found in 58% of the immature
      spines and in 48% of the adult spines. Less than 50% of the small spines at
      either age contained SER, suggesting that other mechanisms, such as cytoplasmic
      buffers, regulate ion fluxes within their small volumes. In contrast, >80% of the
      large mushroom spines of the adult had a spine apparatus, an organelle containing
      stacks of SER and dense-staining plates. Reconstructed SER occupied 0.001-0.022
      microm3, which was only 2-3.5% of the total spine volume; however, the convoluted
      SER membranes had surface areas of 0.12-2.19 microm2, which were 12 to 40% of the
      spine surface area. Coated vesicles and multivesicular bodies occurred in some
      spines, suggesting local endocytotic activity. Smooth vesicles and tubules of SER
      were found in continuity with the spine plasma membrane and margins of the
      postsynaptic density (PSD), respectively, suggesting a role for the SER in the
      addition and recycling of spine membranes and synapses. The amount of SER in the
      parent dendrites was proportional to the number of spines and synapses
      originating along their lengths. These measurements support the hypothesis that
      the SER regulates the ionic and structural milieu of some, but not all,
      hippocampal dendritic spines.

PMID- 8987749
TI  - Functional properties of AMPA and NMDA receptors expressed in identified types of
      basal ganglia neurons.
AB  - AMPA- and NMDA-type glutamate receptors (AMPARs and NMDARs) mediate excitatory
      synaptic transmission in the basal ganglia and may contribute to excitotoxic
      injury. We investigated the functional properties of AMPARs and NMDARs expressed
      by six main types of basal ganglia neurons in acute rat brain slices (principal
      neurons and cholinergic interneurons of striatum, GABAergic and dopaminergic
      neurons of substantia nigra, globus pallidus neurons, and subthalamic nucleus
      neurons) using fast application of glutamate to nucleated and outside-out
      membrane patches. AMPARs in different types of basal ganglia neurons were
      functionally distinct. Those expressed in striatal principal neurons exhibited
      the slowest gating (desensitization time constant tau = 11.5 msec, 1 mM
      glutamate, 22 degrees C), whereas those in striatal cholinergic interneurons
      showed the fastest gating (desensitization time constant tau = 3.6 msec). The
      lowest Ca2+ permeability of AMPARs was observed in nigral dopaminergic neurons
      (PCa/PNa = 0.10), whereas the highest Ca2+ permeability was found in subthalamic
      nucleus neurons (PCa/PNa = 1.17). NMDARs of different types of basal ganglia
      neurons were less variable in their functional properties; those expressed in
      nigral dopaminergic neurons exhibited the slowest gating (deactivation time
      constant of predominant fast component tau1 = 150 msec, 100 microM glutamate),
      and those of globus pallidus neurons showed the fastest gating (tau1 = 67 msec).
      The Mg2+ block of NMDARs was similar; the average chord conductance ratio g
      60mV/g+40mV was 0.18-0.22 in 100 microM external Mg2+. Hence, AMPARs expressed in
      different types of basal ganglia neurons are markedly diverse, whereas NMDARs are
      less variable in functional properties that are relevant for excitatory synaptic
      transmission and neuronal vulnerability.

PMID- 8987750
TI  - Induction of cell proliferation by fibroblast and insulin-like growth factors in
      pure rat inner ear epithelial cell cultures.
AB  - Proliferation of supporting cells in the inner ear is the early major event
      occurring during hair cell regeneration after acoustic trauma or aminoglycoside
      treatment. In the present study, we examined the possible influence of 30 growth
      factors on the proliferation of pure rat utricular epithelial cells in culture.
      Utricular epithelial sheets were separated and partially dissociated from early
      postnatal rats via a combined enzymatic and mechanical method. The cultured
      utricular epithelial cells expressed exclusively epithelial cell antigens, but
      not fibroblast, glial, or neuronal antigens. With tritiated thymidine
      incorporation assays, we found that several fibroblast growth factor (FGF) family
      members, insulin-like growth factor-1 (IGF-1), IGF-2, transforming growth factor
      alpha (TGF-alpha), and epidermal growth factor (EGF), stimulated proliferation of
      the utricular epithelial cells. In contrast, neurotrophins and other growth
      factors did not elicit any detectable mitogenic effects. Among all of the growth
      factors examined, FGF-2 was the most potent mitogen. When FGF-2 was added in
      combination with IGF-1 or TGF-alpha to the medium, combined effects were seen.
      These results were confirmed with BrdU immunocytochemistry. Thus, the present
      culture system provides a rapid and reliable assay system to screen novel growth
      factors involved in proliferation of mammalian inner ear supporting cells.
      Furthermore, immunostainings revealed that the cultured utricular epithelial
      cells expressed FGF and IGF-1 receptors, and utricular hair cells produced FGF-2
      in vivo. The addition of neutralizing antibodies against FGF-2 or IGF-1 to the
      cultures significantly inhibited the utricular epithelial cell proliferation.
      This work suggests that FGF-2 and IGF-1 may regulate the proliferation step
      during hair cell development and regeneration.

PMID- 8987752
TI  - Actin plays a role in both changes in cell shape and gene-expression associated
      with Schwann cell myelination.
AB  - Schwann cell (SC) differentiation into a myelinating cell requires concurrent
      interactions with basal lamina and an axon destined for myelination. As SCs
      differentiate, they undergo progressive morphological changes and initiate myelin
      specific gene expression. We find that disrupting actin polymerization with
      cytochalasin D (CD) inhibits myelination of SC/neuron co-cultures. Basal lamina
      is present, neurons are healthy, and the inhibition is reversible. Electron
      microscopic analysis reveals that actin plays a role at two stages of SC
      differentiation. At 0.75-1.0 microg/ml CD, SCs do not differentiate and appear as
      "rounded" cells in contact with axons. This morphology is consistent with
      disruption of actin filaments and cell shape changes. However, at 0.25 microg/ml
      CD, SCs partially differentiate; they elongate and segregate axons but generally
      fail to form one-to-one relationships and spiral around the axon. In situ
      hybridizations reveal that SCs in CD-treated cultures do not express mRNAs
      encoding the myelin-specific proteins 2',3'-cyclic nucleotide phosphodiesterase
      (CNP), myelin-associated glycoprotein (MAG), and P0. Our results suggest that at
      the lower CD dose, SCs commence differentiation as evidenced by changes in cell
      shape but are unable to elaborate myelin lamellae because of a lack of myelin
      specific mRNAs. We propose that F-actin influences myelin-specific gene
      expression in SCs.

PMID- 8987751
TI  - Growth factor-induced transcription of GluR1 increases functional AMPA receptor
      density in glial progenitor cells.
AB  - We analyzed the effects of two growth factors that regulate oligodendrocyte
      progenitor (O-2A) development on the expression of glutamate receptor (GluR)
      subunits in cortical O-2A cells. In the absence of growth factors, GluR1 was the
      AMPA subunit mRNA expressed at the lowest relative level. Basic fibroblast growth
      factor (bFGF) caused an increase in GluR1 and GluR3 steady-state mRNA levels.
      Platelet-derived growth factor (PDGF) did not modify the mRNA levels for any of
      the AMPA subunits but selectively potentiated the effects of bFGF on GluR1 mRNA
      (4.5-fold increase). The kainate-preferring subunits GluR7, KA1, and KA2 mRNAs
      were increased by bFGF, but these effects were not modified by cotreatment with
      PDGF. Nuclear run-on assays demonstrated that PDGF+bFGF selectively increased the
      rate of GluR1 gene transcription (2.5-fold over control). Western blot analysis
      showed that GluR1 protein levels were increased selectively (sixfold over
      control) by PDGF+bFGF. Functional expression was assessed by rapid application of
      AMPA to cultured cells. AMPA receptor current densities (pA/pF) were increased
      nearly fivefold in cells treated with PDGF+bFGF, as compared with untreated
      cells. Further, AMPA receptor channels in cells treated with PDGF+bFGF were more
      sensitive to voltage-dependent block by intracellular polyamines, as expected
      from the robust and selective enhancement of GluR1 expression. Our combined
      molecular and electrophysiological findings indicate that AMPA receptor function
      can be regulated by growth factor-induced changes in the rate of gene
      transcription.

PMID- 8987753
TI  - Postnatal development of corticospinal projections from motor cortex to the
      cervical enlargement in the macaque monkey.
AB  - The postnatal development of corticospinal projections was investigated in 11
      macaques by means of the anterograde transport of wheat germ agglutin-horseradish
      peroxidase injected into the primary motor cortex hand area. Although the fibers
      of the corticospinal tract reached all levels of the spinal cord white matter at
      birth, their penetration into the gray matter was far from complete. At birth, as
      in the adult, corticospinal projections were distributed to the same regions of
      the intermediate zone, although they showed marked increases in density during
      the first 5 months. The unique feature of the primate corticospinal tract, namely
      direct cortico-motoneuronal projections to the spinal motor nuclei innervating
      hand muscles, was not present to a significant extent at birth. The density of
      these cortico-motoneuronal projections increased rapidly during the first 5
      months, followed by a protracted period extending into the second year of life.
      The densest corticospinal terminations occupied only 40% of the hand motor nuclei
      in the first thoracic segment at 1 month, 73% at 5 months, and 75.5% at 3 years.
      A caudo-rostral gradient of termination density within the hand motor nuclei was
      present throughout development and persisted into the adult. As a consequence,
      the more caudal the segment within the cervical enlargement, the earlier the
      adult pattern of projection density was reached. No transitory corticospinal
      projections were found. The continuous postnatal expansion of cortico
      motoneuronal projections to hand motor nuclei in primates is in marked contrast
      to the retraction of exuberant projections that characterizes the development of
      other sensory and motor pathways in subprimates.

PMID- 8987754
TI  - An electrophysiological study of the postnatal development of the corticospinal
      system in the macaque monkey.
AB  - Postnatal development of the corticospinal system was investigated in 13 macaques
      using noninvasive transcranial magnetic stimulation (TMS) of the motor cortex and
      direct electrical stimulation of corticospinal axons in the medullary pyramid and
      spinal cord. The latency of antidromic corticospinal volleys evoked from the
      pyramid and recorded from the motor cortex decreased dramatically during the
      first postnatal months. Our data predict that conduction velocity (CV) of the
      fastest corticospinal neurons over their cranial course would reach adult values
      at approximately 11 months. The CV of corticospinal neurons in the spinal cord
      increased with age but with a slower time course. In the neonate, the fastest
      spinal CV was estimated at 7.8 m/sec, approximately 10 times slower than in
      adults (mean 80.0 m/sec). Our data predict that full myelination of corticospinal
      axons in the spinal cord would not occur until approximately 36 months. No short
      latency EMG responses were elicited in arm and hand muscles by TMS until 3 months
      of age; TMS thresholds were high initially and then fell progressively with age.
      When corrected for body size, relative latencies of EMG responses showed an
      exponential decrease during the first postnatal months. Our data are consistent
      with the hypothesis that fine finger movements are not observed before functional
      CM connections are well established and that rapid changes in the physiological
      properties of the corticospinal system coincide with the period in which
      precision grip is known to mature (3-6 months). However, corticospinal
      development continues long after simple measures of dexterity indicate functional
      maturity, and these changes may contribute to the improved speed and coordination
      of skilled hand tasks.

PMID- 8987756
TI  - Postnatal development of binocular disparity sensitivity in neurons of the
      primate visual cortex.
AB  - In macaque monkeys, the age at which neurons in the primary visual cortex (V1)
      become sensitive to interocular image disparities, a prerequisite for stereopsis,
      is a matter of conjecture. To resolve this fundamental issue in binocular vision
      development, we measured the responsiveness of individual V1 neurons in
      anesthetized and paralyzed infant monkeys as a function of the relative,
      interocular, spatial phase of dichoptic sine-wave gratings. We found that an
      adult-like proportion of units were sensitive to interocular image disparity as
      early as the sixth postnatal day, several weeks before the onset age for
      stereopsis in monkeys. The ocular dominance distributions of cells in infant
      monkeys were also indistinguishable from those of adults. Thus, at or only a few
      days after birth, V1 neurons are capable of combining neural signals from the two
      eyes as in adults and are sensitive to interocular image disparities. However,
      the monocular spatial-frequency response properties of these disparity-sensitive
      units were immature, and their overall responsiveness was far lower than that in
      adults. During the first 4 postnatal weeks, both the spatial frequency response
      properties and the peak response amplitude rapidly improved, which resulted in a
      corresponding increase in the absolute sensitivity of individual units to
      interocular disparity. The results demonstrate that early binocular vision
      development in monkeys is not constrained by a paucity of disparity-sensitive V1
      neurons but, instead, by the relative immaturity of the spatial response
      properties and the overall unresponsiveness of existing disparity-sensitive
      neurons.

PMID- 8987755
TI  - Maturation of neuronal form and function in a mouse thalamo-cortical circuit.
AB  - Postnatal development of physiological properties underlying slow intrathalamic
      oscillations was studied by whole-cell recording from synaptically coupled
      neurons of the reticular nucleus (RTN) and ventral posterior nucleus (VPN) of
      mouse brain slices in vitro and compared with the morphological development of
      dye-injected cells. Between postnatal days 3 and 11 (P3-P11), progressive changes
      in RTN and VPN neurons included shortening of the membrane time constant,
      decreasing input resistance, and lowering of the resting membrane potential
      (RMP). Low-threshold Ca2+ spikes (LTS) were present from P3, but their capacity
      to sustain multispike bursts was limited before P11. Synaptic responses were
      evoked in RTN and VPN neurons by electrical stimulation of the internal capsule
      from P3. Younger RTN neurons responded with a single spike, but their capacity to
      fire bursts gradually improved as the RMP reached levels below the LTS activation
      potential. Concomitantly, as the reversal potential of the inhibitory
      postsynaptic potential in VPN neurons became more negative, its capacity to
      deinactivate the LTS increased, and rebound bursts that could maintain
      oscillations were produced; sustained oscillations became the typical response to
      internal capsule stimulation at P12. The functional maturation of the
      intrathalamic circuitry, particularly between P10 and P14, occurs in parallel
      with the morphological maturation (size, dendritic growth, and dendritic field
      structure) of individual RTN and VPN neurons, as studied by confocal microscopy.
      Maturation of RTN cells led that of VPN cells by 2-3 d. The appearance of
      intrathalamic oscillations is probably correlated with the appearance of slow
      wave sleep in postnatal animals.

PMID- 8987757
TI  - Synaptic integration of functionally diverse pallidal information in the
      entopeduncular nucleus and subthalamic nucleus in the rat.
AB  - To determine the principles of synaptic innervation of neurons in the
      entopeduncular nucleus and subthalamic nucleus by neurons of functionally
      distinct regions of the pallidal complex, double anterograde labeling was carried
      out at both light and electron microscopic levels in the rat. Deposits of the
      anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran
      amine were placed in different functional domains of the pallidal complex in the
      same animals. The tracer deposits in the ventral pallidum and the globus pallidus
      gave rise to GABA-immunopositive projections to the entopeduncular nucleus, the
      subthalamic nucleus, and the more medial lateral hypothalamus that were largely
      segregated but overlapped at the interface between the two fields of projection.
      In these regions the proximal parts of individual neurons in the entopeduncular
      nucleus, lateral hypothalamus, and subthalamic nucleus received synaptic input
      from terminals derived from both the ventral pallidum and the globus pallidus.
      Furthermore, the analysis of the afferent synaptic input to the dendrites of
      neurons in the subthalamic nucleus that cross functional boundaries of the
      nucleus defined by the pallidal inputs, revealed that terminals with the
      morphological and neurochemical characteristics of those derived from the
      pallidal complex make synaptic contact with all parts of the dendritic tree,
      including distal regions. It is concluded that functionally diverse information
      carried by the descending projections of the pallidal complex is synaptically
      integrated by neurons of the entopeduncular nucleus, lateral hypothalamus, and
      subthalamic nucleus by two mechanisms. First, neurons located at the interface
      between functionally distinct, but topographically adjacent, projections could
      integrate diverse information by means of the synaptic convergence at the level
      of the cell body and proximal dendrites. Second, because the distal dendrites of
      neurons in the subthalamic nucleus receive input from the pallidum, those that
      extend across two distinct domains of pallidal input could also provide the
      morphological basis of integration.

PMID- 8987758
TI  - GDNF reduces drug-induced rotational behavior after medial forebrain bundle
      transection by a mechanism not involving striatal dopamine.
AB  - Parkinson's disease (PD) is characterized by the progressive loss of the
      substantia nigra (SN) dopaminergic neurons projecting to the striatum.
      Neurotrophic factors may have the potential to prevent or slow down the
      degenerative process occurring in PD. To that end, we examined whether low
      amounts of glial cell line-derived neurotrophic factor (GDNF) continuously
      released from polymer-encapsulated genetically engineered cells are able to
      prevent the loss of tyrosine hydroxylase immunoreactivity (TH-IR) in SN neurons
      and ameliorate the amphetamine-induced rotational asymmetry in rats that have
      been subjected to a unilateral medial forebrain bundle (MFB) axotomy. Baby
      hamster kidney (BHK) cells transfected with the cDNA for GDNF were encapsulated
      in a polymer fiber and implanted unilaterally at a location lateral to the MFB
      and rostral to the SN. ELISA assays before implantation show that the capsules
      release approximately 5 ng of GDNF/capsule per day. One week later, the MFB was
      axotomized unilaterally ipsilateral to the capsule placement. Seven days later,
      the animals were tested for amphetamine-induced rotational asymmetry and killed.
      The striatum was excised and analyzed either for catecholamine content or TH-IR,
      while the SN was immunostained for the presence of TH-IR. GDNF did not prevent
      the loss of dopamine in the striatum. However, GDNF significantly rescued TH-IR
      neurons in the SN pars compacta. Furthermore, GDNF also significantly reduced the
      number of turns per minute ipsilateral to the lesion under the influence of
      amphetamine. Improvement of rotational behavior in the absence of dopaminergic
      striatal reinnervation may reflect neuronal plasticity in the SN, as suggested by
      the dendritic sprouting observed in animals receiving GDNF. These results
      illustrate that the continuous release of low levels of GDNF close to the SN is
      capable of protecting the nigral dopaminergic neurons from an axotomy-induced
      lesion and significantly improving pharmacological rotational behavior by a
      mechanism other than dopaminergic striatal reinnervation.

PMID- 8987759
TI  - Registration of neural maps through value-dependent learning: modeling the
      alignment of auditory and visual maps in the barn owl's optic tectum.
AB  - In the optic tectum (OT) of the barn owl, visual and auditory maps of space are
      found in close alignment with each other. Experiments in which such alignment has
      been disrupted have shown a considerable degree of plasticity in the auditory
      map. The external nucleus of the inferior colliculus (ICx), an auditory center
      that projects massively to the tectum, is the main site of plasticity; however,
      it is unclear by what mechanisms the alignment between the auditory map in the
      ICx and the visual map in the tectum is established and maintained. In this
      paper, we propose that such map alignment occurs through a process of value
      dependent learning. According to this paradigm, value systems, identifiable with
      neuromodulatory systems having diffuse projections, respond to innate or acquired
      salient cues and modulate changes in synaptic efficacy in many brain regions. To
      test the self-consistency of this proposal, we have developed a computer model of
      the principal neural structures involved in the process of auditory localization
      in the barn owl. This is complemented by simulations of aspects of the barn owl
      phenotype and of the experimental environment. In the model, a value system is
      activated whenever the owl carries out a foveation toward an auditory stimulus. A
      term representing the diffuse release of a neuromodulator interacts with local
      pre- and postsynaptic events to determine synaptic changes in the ICx. Through
      large-scale simulations, we have replicated a number of experimental observations
      on the development of spatial alignment between the auditory and visual maps
      during normal visual experience, after the retinal image is shifted through
      prismatic goggles, and after the reestablishment of normal visual input. The
      results suggest that value-dependent learning is sufficient to account for the
      registration of auditory and visual maps of space in the OT of the barn owl, and
      they lead to a number of experimental predictions.

PMID- 8987760
TI  - Human brain language areas identified by functional magnetic resonance imaging.
AB  - Functional magnetic resonance imaging (FMRI) was used to identify candidate
      language processing areas in the intact human brain. Language was defined broadly
      to include both phonological and lexical-semantic functions and to exclude
      sensory, motor, and general executive functions. The language activation task
      required phonetic and semantic analysis of aurally presented words and was
      compared with a control task involving perceptual analysis of nonlinguistic
      sounds. Functional maps of the entire brain were obtained from 30 right-handed
      subjects. These maps were averaged in standard stereotaxic space to produce a
      robust "average activation map" that proved reliable in a split-half analysis. As
      predicted from classical models of language organization based on lesion data,
      cortical activation associated with language processing was strongly lateralized
      to the left cerebral hemisphere and involved a network of regions in the frontal,
      temporal, and parietal lobes. Less consistent with classical models were (1) the
      existence of left hemisphere temporoparietal language areas outside the
      traditional "Wernicke area," namely, in the middle temporal, inferior temporal,
      fusiform, and angular gyri; (2) extensive left prefrontal language areas outside
      the classical "Broca area"; and (3) clear participation of these left frontal
      areas in a task emphasizing "receptive" language functions. Although partly in
      conflict with the classical model of language localization, these findings are
      generally compatible with reported lesion data and provide additional support for
      ongoing efforts to refine and extend the classical model.

PMID- 8987761
TI  - Electrophysiological and immunocytochemical evidence for a cGMP-mediated
      inhibition of subfornical organ neurons by nitric oxide.
AB  - The activation of neurons in the subfornical organ (SFO) by angiotensin II
      (AngII) is well established and is widely regarded as the basis for the AngII
      induced increase in water intake. Application of the nitric oxide (NO) donor
      sodium nitroprusside (SNP) led to an inhibition of the spontaneous electrical
      activity in 96% of the neurons sensitive for SNP (n = 50). In addition, the
      firing rate in 60% of the neurons inhibited by SNP decreased in response to
      superfusion with the natural substrate of the NO synthase (NOS) L-arginine
      whereas 70% increased their frequency after application of the NOS blocker NG
      monomethyl-L-arginine (L-NMMA; n = 10). The inhibitory effect of SNP could be
      mimicked by application of membrane-permeable 8-Br-cGMP. The presence of nNOS,
      the neuronal isoform of NOS, was demonstrated immunocytochemically and using the
      NADPH-diaphorase technique on SFO slices. Using a highly selective antibody
      against cGMP in formaldehyde-fixed tissue, the NO donors SNP, 3
      morpholinosydnonimine (SIN-1), and S-nitroso-N-acetyl-DL-penicillamine (SNAP)
      caused a strong increase in cGMP formation when applied under the same conditions
      as used for the electrophysiological recordings. These electrophysiological
      results suggest an important role for NO in SFO-mediated responses and offer a
      plausible explanation for the in vivo-observed opposite effects of AngII and NO
      on water intake.

PMID- 8987762
TI  - Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large
      fiber sensory neuropathy.
AB  - Chronic treatment of adult rats for 2-3 weeks with high doses of pyridoxine
      (vitamin B6) produced a profound proprioceptive loss, similar to that found in
      humans overdosed with this vitamin or treated with the chemotherapeutic agent
      cisplatin. Pyridoxine toxicity was manifest as deficits in simple and precise
      locomotion and sensory nerve function and as degeneration of large-diameter/large
      fiber spinal sensory neurons. As assessed quantitatively in a beam-walking task
      and by EMG recording of H waves evoked by peripheral nerve stimulation,
      coadministration of the neurotrophic factor neurotrophin-3 (NT-3; 5-20 mg . kg-1
      . d-1, s.c.) during chronic pyridoxine treatment largely attenuated the
      behavioral and electrophysiological sequelae associated with pyridoxine toxicity.
      Furthermore, NT-3 administration prevented degeneration of sensory fibers in the
      dorsal column of the spinal cord. These data are consistent with the evidence
      that NT-3 is a target-derived neurotrophic factor for muscle sensory afferents
      and suggest that pharmacological doses of NT-3 may be beneficial in the treatment
      of large-fiber sensory neuropathies.

PMID- 8987763
TI  - Deprivation state switches the neurobiological substrates mediating opiate reward
      in the ventral tegmental area.
AB  - The population of mesolimbic dopaminergic neurons is believed to be a primary
      site at which opiates produce their rewarding effects. Using an unbiased,
      counterbalanced place conditioning paradigm, we reexamined the contribution made
      by these cells to the rewarding properties of morphine. Rats were conditioned
      such that distinct environments were paired with an intra-ventral tegmental area
      (VTA) microinfusion of either 500 ng per 0.5 microl per side morphine or 0. 5
      microl per side sterile saline. Furthermore, rats were conditioned either
      previously drug-naive or while in a motivational state of opiate dependence and
      withdrawal. We report that pretreatment with the broad-spectrum dopamine
      antagonist alpha-flupentixol blocked the acquisition of conditioned place
      preferences for environments paired with morphine microinjections directly into
      the VTA in opiate-dependent and withdrawn, but not in previously drug-naive,
      rats. Lesions of the tegmental pedunculopontine nucleus (TPP) produced exactly
      the opposite pattern of results. TPP lesions blocked the acquisition of
      conditioned place preferences for environments paired with VTA morphine
      microinjections in previously drug-naive, but not in opiate-dependent and
      withdrawn, rats. These data double-dissociate two independent reward substrates
      within the VTA itself and suggest that deprivation state selects which of these
      two substrates will be active. Furthermore, these findings are the first to
      demonstrate a nondopaminergic substrate for reward within the VTA itself.

PMID- 8987764
TI  - Age-related differences in neural activity during memory encoding and retrieval:
      a positron emission tomography study.
AB  - Positron emission tomography (PET) was used to compare regional cerebral blood
      flow (rCBF) in young (mean 26 years) and old (mean 70 years) subjects while they
      were encoding, recognizing, and recalling word pairs. A multivariate partial
      least-squares (PLS) analysis of the data was used to identify age-related neural
      changes associated with (1) encoding versus retrieval and (2) recognition versus
      recall. Young subjects showed higher activation than old subjects (1) in left
      prefrontal and occipito-temporal regions during encoding and (2) in right
      prefrontal and parietal regions during retrieval. Old subjects showed relatively
      higher activation than young subjects in several regions, including insular
      regions during encoding, cuneus/precuneus regions during recognition, and left
      prefrontal regions during recall. Frontal activity in young subjects was left
      lateralized during encoding and right-lateralized during recall [hemispheric
      encoding/retrieval asymmetry (HERA)], whereas old adults showed little frontal
      activity during encoding and a more bilateral pattern of frontal activation
      during retrieval. In young subjects, activation in recall was higher than that in
      recognition in cerebellar and cingulate regions, whereas recognition showed
      higher activity in right temporal and parietal regions. In old subjects, the
      differences in blood flow between recall and recognition were smaller in these
      regions, yet more pronounced in other regions. Taken together, the results
      indicate that advanced age is associated with neural changes in the brain systems
      underlying encoding, recognition, and recall. These changes take two forms: (1)
      age-related decreases in local regional activity, which may signal less efficient
      processing by the old, and (2) age-related increases in activity, which may
      signal functional compensation.

PMID- 8987765
TI  - Regulation of a putative neurotransmitter effect of corticotropin-releasing
      factor: effects of adrenalectomy.
AB  - This study tested the hypothesis that endogenous glucocorticoids regulate a
      putative neurotransmitter function of corticotropin-releasing factor (CRF) in the
      locus coeruleus (LC). LC spontaneous discharge and activation by
      intracerebroventricularly administered CRF, hypotensive challenge, sciatic nerve
      stimulation, and carbachol were compared in adrenalectomized and sham-operated
      halothane-anesthetized rats. LC spontaneous discharge was higher in
      adrenalectomized versus sham-operated rats. Intracoerulear microinfusion of a CRF
      antagonist decreased LC discharge rates of adrenalectomized rats to rates
      comparable with those observed in sham-operated rats but had no effect in sham
      operated rats. The CRF dose-response curve was shifted in a complex manner in
      adrenalectomized rats, suggesting that a proportion of CRF receptors were
      occupied before CRF administration, and low doses of CRF were additive. Higher
      doses of CRF produced effects that were greater than predicted by simple
      additivity. Hypotensive challenge increased LC discharge rates of
      adrenalectomized rats by a magnitude greater than that predicted on the basis of
      additivity. In contrast, LC responses to carbachol and sciatic nerve stimulation
      were similar in both groups. The results suggest that adrenalectomy enhances
      tonic and stress-induced CRF release within the LC and also alters postsynaptic
      sensitivity of LC neurons to CRF. Because adrenalectomy also alters release of
      neurohormone CRF, the present study suggests that CRF actions as a neurohormone
      and as a neurotransmitter in the LC may be co-regulated. Such parallel regulation
      may underlie the coexistence of neuroendocrine and noradrenergic dysfunctions in
      stress-related psychiatric disorders.

PMID- 8987766
TI  - Functional stages in the formation of human long-term motor memory.
AB  - Previous research has demonstrated that the primate CNS has the ability to learn
      and store multiple and conflicting visuo-motor maps. Here we studied the ability
      of human subjects to learn to make reaching movements while interacting with one
      of two conflicting mechanical environments as produced by a robotic manipulandum.
      We demonstrate that two motor maps may be learned and retained, but only if the
      training sessions in the tasks are separated by an interval of approximately 5
      hr. If the interval is shorter, learning of the second map begins with an
      internal model appropriate for the first task and performance in the second task
      is significantly impaired. Analysis of the after-effects suggests that with a
      short temporal distance, learning of the second task leads to an unlearning of
      the internal model for the first. With the longer temporal distance, learning of
      the second task starts with an unbiased internal model, and performance
      approaches that of naives. Furthermore, the memory of the consolidated skill
      lasts for at least 5 months after training. These results argue for a distinct
      change in the state of resistance of motor memory (to disruption) within a few
      hours after acquisition. We suggest that motor practice results in memories that
      have at least two functional components: soon after completion of practice, one
      component fades while another is strengthened. A further experiment suggests that
      the hypothetical first stage is not merely a gateway to long-term memory, but
      also temporary storage for items of information, whether new or old, for use in
      the near-term. Our results raise the possibility that there are distinct neuronal
      mechanisms for representation of the two functional stages of motor memory.

PMID- 8987767
TI  - Nitric oxide production in rat thalamus changes with behavioral state, local
      depolarization, and brainstem stimulation.
AB  - Since its discovery as a putative neurotransmitter in the CNS, several functional
      roles have been suggested for nitric oxide (NO). However, few studies have
      investigated the role of NO in natural physiology. Because NO synthase (NOS) has
      been localized in regions believed to be important for attention and arousal, we
      hypothesized that NO production would be state-dependent. To test this
      hypothesis, we used in vivo microdialysis, coupled with the hemoglobin-trapping
      technique, to monitor extracellular NO concentrations in rat thalamus during
      wake, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. The thalamus is
      known to receive a massive innervation from the NOS/cholinergic neurons in the
      mesopontine brainstem, which have been suggested to play a key role in EEG
      desynchronized states. To test whether thalamic NO output was sensitive to
      neuronal-dependent changes in the mesopontine brainstem, we measured thalamic NO
      concentration in response to electrical stimulation in the laterodorsal tegmentum
      (LDT) of anesthetized rats. Finally, the calcium dependence of NO release was
      tested by local depolarization with a high potassium dialysate or by addition of
      a calcium chelator. The results showed that (1) extracellular NO concentrations
      in the thalamus were high during wake and REM sleep and significantly lower
      during SWS, (2) thalamic NO release increased in response to LDT stimulation in
      both a site-specific and tetrodotoxin (TTX)-dependent manner, and (3) NO
      production was calcium-dependent. These data suggest that thalamic NO production
      may play a role in arousal.

PMID- 8987768
TI  - Unique postsynaptic signaling at the hair cell efferent synapse permits calcium
      to evoke changes on two time scales.
AB  - The cholinergic efferent fibers to the outer hair cells (OHCs) of the mammalian
      cochlea suppress sound-evoked activity of the auditory nerve on two time scales
      via one nicotinic receptor. A rapid action (tens of milliseconds) is responsible
      for modulating auditory nerve responses to acoustic stimulation. A slower action
      (tens of seconds) may protect the ear from acoustic overstimulation. The rapid
      action is likely caused by calcium influx through the nicotinic receptor that
      leads to opening of calcium-activated potassium (KCa) channels, but the mechanism
      of the slower action has not been explained. To investigate this mechanism, we
      perfused the cochlea with agents that alter intracellular calcium release and
      uptake. Both fast and slow effects were enhanced by perfusion of the cochlea with
      ryanodine, an agonist of calcium-induced calcium release (CICR). Antagonists of
      sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), cyclopiazonic acid,
      and thapsigargin (1) selectively enhanced the magnitude of slow effects, (2)
      prevented the diminution of slow effects with continued efferent stimulation, and
      (3) spread the range of frequencies over which slow effects were observed. We
      propose that the slow effect is attributable to release of calcium from the
      subsurface cisterna of the OHC, perhaps triggered by CICR from the synaptic
      cisterna; the two time scales of efferent action may result from the unique
      arrangement of the two cisternae in the baso-lateral region of the OHC.

PMID- 8987769
TI  - Anatomic organization of the basilar pontine projections from prefrontal cortices
      in rhesus monkey.
AB  - In our ongoing attempt to determine the anatomic substrates that could support a
      cerebellar contribution to cognitive processing, we investigated the prefrontal
      cortical projections to the basilar pons. A detailed understanding of these
      pathways is needed, because the prefrontal cortex is critical for a number of
      complex cognitive operations, and the corticopontine projection is the obligatory
      first step in the corticopontocerebellar circuit. Prefrontopontine connections
      were studied using the autoradiographic technique in rhesus monkey. The pontine
      projections were most prominent and occupied the greatest rostrocaudal extent of
      the pons when derived from the dorsolateral prefrontal convexity, including areas
      8Ad, 9/46d, and 10. Lesser pontine projections were observed from the medial
      prefrontal convexity and area 45B in the inferior limb of the arcuate sulcus. In
      contrast, ventral prefrontal and orbitofrontal cortices did not demonstrate
      pontine projections. The prefrontopontine terminations were located
      preferentially in the paramedian nucleus and in the medial parts of the
      peripeduncular nucleus, but each cortical area appeared to have a unique
      complement of pontine nuclei with which it is connected. The existence of these
      corticopontine pathways from prefrontal areas concerned with multiple domains of
      higher-order processing is consistent with the hypothesis that the cerebellum is
      an essential node in the distributed corticosubcortical neural circuits
      subserving cognitive operations.

PMID- 8987770
TI  - Mechanosensory neurons innervating Aplysia siphon encode noxious stimuli and
      display nociceptive sensitization.
AB  - Numerous studies of learning and memory in Aplysia have focused on primary
      mechanosensory neurons innervating the siphon and having their somata in the left
      E (LE) cluster of the abdominal ganglion. Although systematic analyses have been
      made of the responses of these LE cells to mechanical stimulation of the tightly
      pinned siphon, little is known about corresponding responses when the siphon is
      unrestrained. The present study demonstrates that LE mechanosensory thresholds in
      the freely moving siphon are much higher than in the pinned siphon. Light tactile
      stimuli adequate to activate central neurons and reflexive siphon movements often
      fail to activate the LE cells when the siphon is unrestrained. Because the LE
      cells display increasing discharge to increasing pressures, with maximal
      activation by crushing or tearing stimuli that cause tissue injury, they satisfy
      accepted definitions of nociceptor. Indeed, they show similarities to vertebrate
      Adelta nociceptors, including a property apparently unique (among primary
      afferents) to nociceptors-sensitization by noxious stimulation of their receptive
      field. Either pinching or pinning the siphon decreases LE cell mechanosensory
      threshold and enhances soma excitability. Such stimuli reduce effective tissue
      compliance and cause neuromodulation that enhances sensory responsiveness. These
      results, and recent descriptions of predatory attacks on Aplysia, suggest that LE
      sensory neurons are tuned to grasping and crushing stimuli that threaten or
      produce bodily harm. LE cell sensitization has effects, resembling hyperalgesia
      and allodynia, that compensate for loss of sensory function during injury and
      help protect against subsequent threats.

PMID- 8987771
TI  - Adult mammalian sensory and motor neurons: roles of endogenous neurotrophins and
      rescue by exogenous neurotrophins after axotomy.
AB  - We have tested the ability of neurotrophins to reverse axotomy-induced changes in
      adult motor and sensory neurons, using the physiological measure of conduction
      velocity. Five weeks after axotomy, sensory and motor conduction velocities were
      greatly reduced. NT-3 at 60 microg/d, pumped directly onto the cut nerve stump,
      largely prevented the change in sensory fibers. Lower doses were less effective,
      and NT-4/5 was without effect. In contrast, both NT-3 and NT-4/5 were effective
      at rescuing motoneurons, with similar dose dependencies. This amelioration of
      physiological deficits in adult mammalian neurons suggests possible therapeutic
      application of neurotrophins. We have also studied the physiological effects of
      neurotrophin deprivation on intact peripheral neurons. After 2 weeks of
      sequestration of trkB ligands (BDNF and NT-4/5), motor, but not sensory, neuron
      conduction was significantly slowed. Sequestration of NT-3 was found to affect
      both motor and sensory fiber velocities but more modestly and only with higher
      doses of sequestering agent. These data therefore suggest that peripherally
      produced neurotrophins are necessary for the maintenance of normal functional
      properties of peripheral neurons.

PMID- 8987772
TI  - Changes in hippocampal circuitry after pilocarpine-induced seizures as revealed
      by opioid receptor distribution and activation.
AB  - The pilocarpine model of temporal lobe epilepsy was used to study the time
      dependent changes in dentate gyrus circuitry after seizures. Seizures caused a
      decrease in mu- and delta-opioid receptor immunoreactive (MOR-IR and DOR-IR,
      respectively) neurons in the hilus and MOR-IR neurons in the granule cell layer.
      Additionally, diffuse DOR-IR, MOR-IR, and GABA immunoreactivities (GABA-IR) were
      increased in the inner molecular layer. Using the in vitro hippocampal slice
      preparation to study the physiological consequences of the anatomical changes, we
      found that the disinhibitory effects of the mu-opioid receptor agonist [D-Ala2,
      MePhe4,Gly-(ol)5]-enkephalin (DAMGO) and the GABAA receptor antagonist
      bicuculline were greatly depressed 5-13 d after pilocarpine injection but
      returned to control levels within 6 weeks. The amplitudes of monosynaptic evoked
      IPSCs and the effects of DAMGO on this parameter were also slightly decreased 5
      13 d after pilocarpine injection but significantly increased at 6 weeks. DAMGO
      significantly decreased the mean amplitude of spontaneous IPSCs (sIPSCs) at 6
      weeks after pilocarpine injection but not in controls. The delta-opioid receptor
      agonist [D-Pen2,5]-enkephalin (DPDPE) principally inhibited excitatory
      transmission in saline-treated animals without affecting either sIPSCs or evoked
      IPSCs. The DPDPE-induced inhibition of excitatory transmission became more
      pronounced at 6 weeks after pilocarpine injection. These results illustrate the
      anatomical reorganization and functional changes in dentate gyrus circuitry
      evident in an animal model of temporal lobe epilepsy and provide evidence of
      compensatory changes after trauma to the hippocampal formation.

PMID- 8987773
TI  - Nitric oxide involvement in Hydra vulgaris very primitive olfactory-like system.
AB  - Hydra feeding response is a very primitive olfactory-like behavior present in a
      multicellular organism. We investigated the role of nitric oxide (NO) in the
      induction and control of hydra feeding response. Under basal conditions, hydra
      specimens produce detectable amounts of nitrite (NO2-), the breakdown product of
      NO. When hydra were incubated with reduced glutathione (GSH), the typical
      activator of feeding response, an increase of basal NO production was observed.
      This effect was inhibited by glutamic or alpha-aminoadipic acids, two GSH
      antagonists, which block GSH-induced feeding response, and by the NO synthase
      (NOS) inhibitor L-NAME. Moreover, we found that hydra possess a calcium-dependent
      (but calmodulin-independent) NOS isoform. By using exogenous NO donors and NOS
      inhibitors, we demonstrated that NO stimulus can participate both in triggering
      tentacular movements and in recruiting neighbor tentacles during hydra feeding
      response. By using dbt2-cGMP, an analog to cGMP, we observed that the NO effect
      was independent of cGMP pathway. Our results strongly implicate NO involvement in
      hydra very primitive feeding behavior, thus confirming its preservation
      throughout evolution.

PMID- 8987774
TI  - 17 alpha-estradiol exerts neuroprotective effects on SK-N-SH cells.
AB  - Estradiol (E2) has been shown to exert organizational, neurotrophic, and
      neuroprotective effects in the CNS. The present study assessed the specificity of
      the neuroprotective effects of estradiol for the potent 17 beta-isomer. SK-N-SH
      cells from a human neuroblastoma cell line, which we have shown to be estrogen
      responsive, were cultured at low or high plating density. Then cells were exposed
      to 17 beta-E2 (0.2 or 2 nM), 17 alpha-E2 (0.2 or 2 nM), or cholesterol,
      testosterone, dihydrotestosterone, progesterone, or corticosterone (all at 2 nM).
      Cultures were insulted by serum deprivation, which caused a profound loss of
      cells. At 1 or 2 d of serum deprivation and steroid hormone replacement, the
      protection afforded cells by the steroid addition was assessed. Serum deprivation
      killed approximately 90% of cells cultured at both low and high plating density.
      Both 17 alpha- and 17 beta-E2 provided protection of SK-N-SH cells at either
      plating density. Further, a 10-fold molar excess of tamoxifen antagonized only
      approximately one-third of the neuroprotective effects of either isomer of
      estradiol, and a 100-fold excess of tamoxifen had no additional effect on the
      neuroprotection by 17 beta-E2. By contrast, none of the other steroids tested
      protected cells from the insult of serum deprivation. These results indicate that
      the neuroprotective effects of estrogens are not attributable to the general
      steroid structure, and the majority of the neuroprotection may not be mediated
      via a tamoxifenantagonized receptor mechanism.

PMID- 8987775
TI  - Plastic neuronal remodeling is impaired in patients with Alzheimer's disease
      carrying apolipoprotein epsilon 4 allele.
AB  - A relationship between the apolipoprotein E (apoE) genotype and the risk to
      develop Alzheimer's disease has been established recently. Apolipoprotein
      synthesis is implicated in developmental processes and in neuronal repair of the
      adult nervous system. In the present study, we investigated the influence of the
      apolipoprotein polymorphism on the severity of neuronal degeneration and the
      extent of plastic dendritic remodeling in Alzheimer's disease. Changes in length
      and arborization of dendrites of Golgi-impregnated neurons in the basal nucleus
      of Meynert, locus coeruleus, raphe magnus nucleus, medial amygdaloid nucleus,
      pedunculopontine tegmental nucleus, and substantia nigra were analyzed after
      three-dimensional reconstruction. Patients with either one or two apoE epsilon 4
      alleles not only showed a more severe degeneration in all areas investigated than
      in patients lacking the apoE 4 allele but also revealed significantly less
      plastic dendritic changes. ApoE epsilon 4 allele copy number, furthermore, had a
      significant effect on the pattern of dendritic arborization. Moreover, the
      relationship between the intensity of dendritic growth and both the extent of
      neuronal degeneration and the stage of the disease seen in patients lacking the
      apoE epsilon 4 allele was very weak in the presence of one epsilon 4 allele and
      completely lost in patients homozygous for the epsilon 4 allele. The results
      provide direct evidence that neuronal reorganization is affected severely in
      patients with Alzheimer's disease carrying the apoE epsilon 4 allele. This
      impairment of neuronal repair might lead to a more rapid functional
      decompensation, thereby contributing to an earlier onset and more rapid
      progression of the disease.

PMID- 8987776
TI  - Nerve growth factor induces apoptosis in human medulloblastoma cell lines that
      express TrkA receptors.
AB  - Neurotrophins act through their cognate receptors to promote the differentiation
      and/or survival of neuronal progenitor cells, immature neurons, and other cells.
      Here, we examined the effects of nerve growth factor (NGF) and its cognate
      receptor (Trk or TrkA) on the survival of a common childhood brain tumor, i.e.,
      medulloblastoma, a tumor that resembles CNS neuroepithelial progenitor cells. To
      do this, we engineered two human medulloblastoma cell lines (i.e., D283MED and
      DAOY cells) to express human TrkA using a retroviral expression vector.
      Surprisingly, NGF-treated medulloblastoma cells expressing the TrkA receptor
      (D283trk and DAOYtrk cells) grown in the presence or absence of serum underwent
      massive apoptosis, but similar treatment did not induce apoptosis in wild-type
      uninfected cells, cells expressing an empty vector, or cells expressing the TrkC
      receptor. Furthermore, D283MED cells engineered to express the human p75 NGF
      receptor (D283p75) also did not undergo apoptosis. Significantly, NGF-induced
      apoptosis in D283trk and DAOYtrk cells can be inhibited by anti-NGF antibodies
      and by K-252a, an inhibitor of TrkA tyrosine phosphorylation and mimicked by high
      concentrations of NT3. Because NGF treatment primarily eliminated D283trk cells
      from the S phase of the cell cycle, this form of NGF-mediated apoptosis is cell
      cycle-dependent. These findings suggest that a NGF/TrkA signal transduction
      pathway could activate apoptotic cell death programs in CNS neuroepithelial
      progenitor cells and in childhood brain tumors.

PMID- 8987777
TI  - An extracellular proteolytic cascade promotes neuronal degeneration in the mouse
      hippocampus.
AB  - Mice lacking the serine protease tissue plasminogen activator (tPA) are resistant
      to excitotoxin-mediated hippocampal neuronal degeneration. We have used genetic
      and cellular analyses to study the role of tPA in neuronal cell death. Mice
      deficient for the zymogen plasminogen, a known substrate for tPA, are also
      resistant to excitotoxins, implicating an extracellular proteolytic cascade in
      degeneration. The two known components of this cascade, tPA and plasminogen, are
      both synthesized in the mouse hippocampus. tPA mRNA and protein are present in
      neurons and microglia, whereas plasminogen mRNA and protein are found exclusively
      in neurons. tPA-deficient mice exhibit attenuated microglial activation as a
      reaction to neuronal injury. In contrast, the microglial response of plasminogen
      deficient mice was comparable to that of wild-type mice, suggesting a tPA
      mediated, plasminogen-independent pathway for activation of microglia. Infusion
      of inhibitors of the extracellular tPA/plasmin proteolytic cascade into the
      hippocampus protects neurons against excitotoxic injury, suggesting a novel
      strategy for intervening in neuronal degeneration.

PMID- 8987778
TI  - Activation of the CED3/ICE-related protease CPP32 in cerebellar granule neurons
      undergoing apoptosis but not necrosis.
AB  - Neuronal apoptosis occurs during nervous system development and after
      pathological insults to the adult nervous system. Inhibition of CED3/ICE-related
      proteases has been shown to inhibit neuronal apoptosis in vitro and in vivo,
      indicating a role for these cysteine proteases in neuronal apoptosis. We have
      studied the activation of the CED3/ICE-related protease CPP32 in two in vitro
      models of mouse cerebellar granule neuronal cell death: K+/serum deprivation
      induced apoptosis and glutamate-induced necrosis. Pretreatment of granule neurons
      with a selective, irreversible inhibitor of CED3/ICE family proteases, ZVAD
      fluoromethylketone, specifically inhibited granule neuron apoptosis but not
      necrosis, indicating a selective role for CED3/ICE proteases in granule neuron
      apoptosis. Extracts prepared from apoptotic, but not necrotic, granule neurons
      contained a protease activity that cleaved the CPP32 substrate Ac-DEVD
      aminomethylcoumarin. Induction of the protease activity was prevented by
      inhibitors of RNA or protein synthesis or by the CED3/ICE protease inhibitor.
      Affinity labeling of the protease activity with an irreversible CED3/ICE protease
      inhibitor, ZVK(biotin)D-fluoromethylketone, identified two putative protease
      subunits, p20 and p18, that were present in apoptotic but not necrotic granule
      neuron extracts. Western blotting with antibodies to the C terminus of the large
      subunit of mouse CPP32 (anti-CPP32) identified p20 and p18 as processed subunits
      of the CPP32 proenzyme. Anti-CPP32 specifically inhibited the DEVD-amc cleaving
      activity, verifying the presence of active CPP32 protease in the apoptotic
      granule neuron extracts. Western blotting demonstrated that the CPP32 proenzyme
      was expressed in granule neurons before induction of apoptosis. These results
      demonstrate that the CED3/ICE homolog CPP32 is processed and activated during
      cerebellar granule neuron apoptosis. CPP32 activation requires macromolecular
      synthesis and CED3/ICE protease activity. The lack of CPP32 activation during
      granule neuron necrosis suggests that proteolytic processing and activation of
      CED3/ICE proteases are specific biochemical markers of apoptosis.

PMID- 8987779
TI  - Cellular localization of the prohormone convertases in the hypothalamic
      paraventricular and supraoptic nuclei: selective regulation of PC1 in
      corticotrophin-releasing hormone parvocellular neurons mediated by
      glucocorticoids.
AB  - The prohormone convertases (PCs) are processing enzymes that activate proproteins
      via cleavage at specific single or pairs of basic residues. The hypothalamic
      paraventricular nucleus (PVN) and supraoptic nucleus (SON) are primary sites of
      biosynthesis of several neuroendocrine hormone precursors, including
      provasopressin (pro-AVP), pro-oxytocin (pro-OT), and procorticotrophin-releasing
      hormone (pro-CRH), which require post-translational processing to yield active
      products. Using in situ hybridization, we observed PC1 and PC5 mRNAs in PVN and
      SON magnocellular neurons, while PC2 mRNA was observed in both magnocellular and
      parvocellular PVN neurons as well as magnocellular SON neurons. Similar to furin,
      PC7 mRNA was expressed throughout the PVN and SON, whereas PACE4 mRNA levels were
      undetectable. Both immunohistochemical and Western blot studies were performed to
      demonstrate the presence of PC proteins and forms in the PVN and SON. Using
      double-labeling in situ hybridization, we examined the cellular colocalization of
      each PC mRNA with pro-AVP, pro-OT, and pro-CRH mRNAs in PVN and SON. PC1 mRNA was
      colocalized with both AVP and OT mRNA in PVN and SON magnocellular neurons. All
      AVP, OT, and CRH neurons expressed PC2. In contrast, PC5 mRNA was colocalized
      only with OT mRNA. We examined the effects of adrenalectomy (ADX) on PVN PC mRNA
      levels. PC1 mRNA levels were increased selectively within CRH/AVP parvocellular
      neurons but were unchanged in PVN magnocellular AVP or OT neurons. These results
      established the anatomical organization of each convertase and proneuropeptide
      substrates in the PVN and SON and suggested potential roles for each enzyme under
      resting and stimulated conditions.

PMID- 8987780
TI  - Role of Ca2+ ions in nicotinic facilitation of GABA release in mouse thalamus.
AB  - Presynaptic nicotinic acetylcholine receptors (nAChRs) are present in many
      regions of the brain and potentially serve as targets for the pharmacological
      action of nicotine in vivo. To investigate their mechanism of action, we
      performed patch-clamp recordings in relay neurons from slices of thalamus sensory
      nuclei. In these nuclei, nAChR activation facilitated the release of the
      inhibitory neurotransmitter GABA. Micromolar concentrations of nicotinic agonists
      increased the frequency of miniature GABAergic synaptic currents and decreased
      the failure rate of evoked synaptic currents. These actions of nicotinic agonists
      were not observed in knock-out mice lacking the beta 2 nAChR subunit gene.
      Nicotinic effects were dependent on extracellular calcium ions, and they
      persisted when calcium was replaced by strontium or barium but not by magnesium.
      Furthermore, in high extracellular calcium concentrations, nicotinic agonists
      evoked an increase in spontaneous release lasting for minutes after removal of
      the agonist. This supports the view that presynaptic nAChRs facilitate the
      release of neurotransmitter by increasing the calcium concentrations in
      presynaptic nerve endings. With use of cadmium and nickel ions as selective
      blockers, it was found that in different sensory nuclei the presynaptic influx of
      calcium could result either from the activation of voltage-dependent calcium
      channels or from a direct influx through nAChR channels. Finally, we propose that
      the nicotinic facilitation of GABAergic transmission may contribute to the
      increase of signal-to-noise ratio observed in the thalamus in vivo during
      arousal.

PMID- 8987781
TI  - Heterogeneity of nicotinic receptor class and subunit mRNA expression among
      individual parasympathetic neurons from rat intracardiac ganglia.
AB  - Neurons have the potential to form thousands of distinct neuronal nicotinic
      receptors from the eight alpha and three beta subunits that currently are known.
      In an effort to determine how much of this potential complexity is realized among
      individual neurons, we examined the nicotinic pharmacological and biophysical
      properties and receptor subunit mRNA expression patterns in individual neurons
      cultured from rat epicardial ganglia. Analysis of the whole-cell pharmacology of
      these neurons showed a diversity of responses to the agonists acetylcholine,
      nicotine, cytisine, and 1,1-dimethyl-4-phenylpiperazinium, suggesting that a
      heterogeneous population of nicotinic receptor classes, or subtypes, is expressed
      by individual neurons. Single-channel analysis demonstrated three distinct
      conductances (18, 24, and 31 pS), with patches from different neurons containing
      different combinations of these channel classes. We used single-cell RT-PCR to
      examine nicotinic acetylcholine receptor (nAChR) subunit mRNA expression by
      individual neurons. Although mRNAs encoding all eight neuronal nAChR subunits for
      which we probed (alpha 2-alpha 5, alpha 7, beta 2-beta 4) were present in
      multicellular cultures, we found that individual epicardial neurons express
      distinct subsets of these nAChR subunit mRNAs. These results suggest that
      individual epicardial neurons express distinct arrays of nAChR subunits and that
      these subunits may assemble into functional receptors with distinct and variable
      subunit composition. This variable receptor subunit expression provides an
      explanation for the diversity of pharmacological and single-channel responses we
      have observed in individual neurons.

PMID- 8987782
TI  - Pathway-specific synaptic plasticity: activity-dependent enhancement and
      suppression of long-term heterosynaptic facilitation at converging inputs on a
      single target.
AB  - To explore mechanisms of long-term, pathway-specific synaptic plasticity, we
      examined consequences of differential stimulation of Aplysia sensorimotor
      connections in culture where two sensory neuron (SN) inputs converge on a single
      target motor cell L7. A single pairing of tetanus in one SN with bath application
      of 5-HT evoked long-term (24 hr) increase in efficacy of the SN connection given
      paired stimulation that was comparable in magnitude to the increase in synaptic
      efficacy evoked with repeated applications of 5-HT. Repeated pairing of tetanus
      in one SN with applications of 5-HT evoked a significant increase in efficacy of
      the SN connection given paired stimuli, and significant reduction in facilitation
      that is normally evoked by repeated applications of 5-HT in the unpaired SN
      connection. Hyperpolarization of L7 or incubation with APV interfered with both
      enhancement of facilitation with paired stimulation and suppression of
      facilitation with unpaired stimulation, but without interfering with long-term
      facilitation evoked either by repeated applications of 5-HT or by a single
      pairing. The results suggest that a single connection can undergo at least two
      forms of activity-dependent, pathway-specific facilitation lasting more than 24
      hr. One form, evoked with a single pairing, is initiated and maintained primarily
      by activity in the presynaptic neuron. The other form, evoked with repeated
      paired stimuli, requires target-dependent activity that differentially modulates
      long-term heterosynaptic facilitation at the converging inputs.

PMID- 8987783
TI  - Activation of hippocampal adenosine A3 receptors produces a desensitization of A1
      receptor-mediated responses in rat hippocampus.
AB  - The adenosine A3 receptor is expressed in brain, but the consequences of
      activation of this receptor on electrophysiological activity are unknown. We have
      characterized the actions of a selective adenosine A3 receptor agonist, 2-chloro
      N6-(3-lodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA), and a selective A3
      receptor antagonist, 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/
      )-dihydropyridine-3,5-dicarboxylate (MRS 1191), in brain slices from rat
      hippocampus. In the CA1 region, activation of A3 receptors had no direct effects
      on synaptically evoked excitatory responses, long-term potentiation, or synaptic
      facilitation. However, activation of A3 receptors with Cl-IB-MECA antagonized the
      adenosine A1 receptor-mediated inhibition of excitatory neurotransmission. The
      effects of Cl-IB-MECA were blocked by pretreatment with MRS 1191, which by itself
      had no effect on A1 receptor-mediated responses. The presynaptic inhibitory
      effects of baclofen and carbachol, mediated via GABA(B) and muscarinic receptors,
      respectively, were unaffected by Cl-IB-MECA. The maximal response to adenosine
      was unchanged, suggesting that the primary effect of Cl-IB-MECA was to reduce the
      affinity of adenosine for the receptor rather than to uncouple it. Similar
      effects could be demonstrated after brief superfusion with high concentrations of
      adenosine itself. Under normal conditions, endogenous adenosine in brain is
      unlikely to affect the sensitivity of A1 receptors via this mechanism. However,
      when brain concentrations of adenosine are elevated (e.g., during hypoxia,
      ischemia, or seizures), activation of A3 receptors and subsequent heterologous
      desensitization of A1 receptors could occur, which might limit the
      cerebroprotective effects of adenosine under these conditions.

PMID- 8987784
TI  - Mechanisms of C5a and C3a complement fragment-induced [Ca2+]i signaling in mouse
      microglia.
AB  - Microglial cells are activated in response to brain insults; the mechanisms of
      this process are not yet understood. One of the important signaling mechanisms
      that might be involved in microglia activation is related to changes in the
      intracellular calcium concentration ([Ca2+]i). Using fluo-3 microfluorimetry, we
      have found that external application of the complement fragment C5a (4-10 nM)
      induced [Ca2+]i elevation in microglial cells in situ in corpus callosum slices.
      Similarly, application of complement fragments C5a (0.1-10.0 nM) or C3a (100 nM)
      generates biphasic [Ca2+]i transients composed of an initial peak followed by a
      plateau in cultured microglia. Incubation of microglial cells for 30 min with
      pertussis toxin (PTX; 1 microgram/ml) inhibited both C5a- and C3a-triggered
      [Ca2+]i responses, suggesting the involvement of PTX-sensitive G-proteins in the
      signal transduction chain. Removal of Ca2+ ions from the extracellular solution
      eliminated the plateau phase and limited the response to the initial peak. The
      restoration of the extracellular Ca2+ concentration within 30-60 sec after the
      beginning of the complement fragment-induced [Ca2+]i elevation led to the
      recovery of the plateau phase. Inhibition of the endoplasmic reticulum Ca2+ pumps
      with 500 nM thapsigargin transiently increased the [Ca2+]i and blocked the
      [Ca2+]i signals in response to subsequent complement fragment application. Our
      data suggest that complement factors induce [Ca2+]i responses by Ca2+ release
      from internal pools and subsequent activation of Ca2+ entry controlled by the
      filling state of the intracellular Ca2+ depots.

PMID- 8987785
TI  - Bicuculline and gabazine are allosteric inhibitors of channel opening of the
      GABAA receptor.
AB  - Anesthetic drugs are known to interact with GABAA receptors, both to potentiate
      the effects of low concentrations of GABA and to directly gate open the ion
      channel in the absence of GABA; however, the site(s) involved in direct gating by
      these drugs is not known. We have studied the ability of alphaxalone (an
      anesthetic steroid) and pentobarbital (an anesthetic barbiturate) to directly
      activate recombinant GABAA receptors containing the alpha 1, beta 2, and gamma 2L
      subunits. Steroid gating was not affected when either of two mutated beta 2
      subunits [beta 2 (Y157S) and beta 2 (Y205S)] are incorporated into the receptors,
      although these subunits greatly reduce the affinity of GABA binding. These
      observations indicate that steroid binding and subsequent channel gating do not
      require these particular residues, as already shown for barbiturates. Bicuculline
      or gabazine (two competitive antagonists of GABA binding) reduced the currents
      elicited by alphaxalone and pentobarbital from wild-type GABAA receptors;
      however, gabazine produced only a partial block of response pentobarbital or
      alphaxalone, and bicuculline only partially blocked responses to pentobarbital.
      These observations indicate that the blockers do not compete with alphaxalone or
      pentobarbital for a single class of sites on the GABAA receptor. Finally, at
      receptors containing alpha 1 beta 2 (Y157S) gamma 2L subunits, both bicuculline
      and gabazine showed weak agonist activity and actually potentiated responses to
      alphaxalone. These observations indicate that the blocking drugs can produce
      allosteric changes in GABAA receptors, at least those containing this mutated
      beta 2 subunit. We conclude that the sites for binding steroids and barbiturates
      do not overlap with the GABA-binding site. Furthermore, neither gabazine nor
      bicuculline competes for binding at the steroid or barbiturate sites. The data
      are consistent with a model in which both gabazine and bicuculline act as
      allosteric inhibitors of channel opening for the GABAA receptor after binding to
      the GABA-binding site.

PMID- 8987786
TI  - The type 1 inositol 1,4,5-trisphosphate receptor gene is altered in the
      opisthotonos mouse.
AB  - The opisthotonos (opt) mutation arose spontaneously in a C57BL/Ks-db2J colony and
      is the only known, naturally occurring allele of opt. This mutant mouse was first
      identified based on its ataxic and convulsive phenotype. Genetic and molecular
      data presented here demonstrate that the type 1 inositol 1,4,5-trisphosphate
      receptor (IP3R1) protein, which serves as an IP3-gated channel to release calcium
      from intracellular stores, is altered in the opt mutant. A genomic deletion in
      the IP3R1 gene removes two exons from the IP3R1 mRNA but does not interrupt the
      translational reading frame. The altered protein is predicted to have lost
      several modulatory sites and is present at markedly reduced levels in opt
      homozygotes. Nonetheless, a strong calcium release from intracellular stores can
      be elicited in cerebellar Purkinje neurons treated with the metabotropic
      glutamate receptor (mGluR) agonist quisqualate (QA). QA activates Group 1 mGluRs
      linked to GTP-binding proteins that stimulate phospholipase C and subsequent
      production of the intracellular messenger IP3, leading to calcium mobilization
      via the IP3R1 protein. The calcium response in opt homozygotes shows less
      attenuation to repeated QA application than in control littermates. These data
      suggest that the convulsions and ataxia observed in opt mice may be caused by the
      physiological dysregulation of a functional IP3R1 protein.

PMID- 8987787
TI  - A transcription-dependent switch controls competence of adult neurons for
      distinct modes of axon growth.
AB  - Although maturing neurons undergo a precipitous decline in the expression of
      genes associated with developmental axon growth, structural changes in axon
      arbors occur in the adult nervous system under both normal and pathological
      conditions. Furthermore, some neurons support extensive regrowth of long axons
      after nerve injury. Analysis of adult dorsal root ganglion (DRG) neurons in
      culture now shows that competence for distinct types of axon growth depends on
      different patterns of gene expression. In the absence of ongoing transcription,
      newly isolated neurons can extend compact, highly branched arbors during the
      first day in culture. Neurons subjected to peripheral axon injury 2-7 d before
      plating support a distinct mode of growth characterized by rapid extension of
      long, sparsely branched axons. A transition from "arborizing" to "elongating"
      growth occurs in naive adult neurons after approximately 24 hr in culture but
      requires a discrete period of new transcription after removal of the ganglia from
      the intact animal. Thus, peripheral axotomy-by nerve crush or during removal of
      DRGs--induces a transcription-dependent change that alters the type of axon
      growth that can be executed by these adult neurons. This transition appears to be
      triggered, in large part, by interruption of retrogradely transported signals,
      because blocking axonal transport in vivo can elicit competence for elongating
      growth in many DRG neurons. In contrast to peripheral axotomy, interruption of
      the centrally projecting axons of DRG neurons in vivo leads to subsequent growth
      in vitro that is intermediate between "arborizing" and "elongating" growth. This
      suggests that the transition between these two modes of growth is a multistep
      process and that individual steps may be regulated separately. These observations
      together suggest that structural remodeling in the adult nervous system need not
      involve the same molecular apparatus as long axon growth during development and
      regeneration.

PMID- 8987788
TI  - Coupling of muscarinic cholinergic receptors and cGMP in nocturnal regulation of
      the suprachiasmatic circadian clock.
AB  - Acetylcholine has long been implicated in nocturnal phase adjustment of circadian
      rhythms, yet the subject remains controversial. Although the suprachiasmatic
      nucleus (SCN), site of the circadian clock, contains no intrinsic cholinergic
      somata, it receives choline acetyltransferase-immunopositive projections from
      basal forebrain and mesopontine tegmental nuclei that contribute to sleep and
      wakefulness. We have demonstrated that the SCN of inbred rats in a hypothalamic
      brain slice is sensitive to cholinergic phase adjustment via muscarinic receptors
      (mAChRs) only at night. We used this paradigm to probe the muscarinic signal
      transduction mechanism and the site(s) gating nocturnal responsiveness. The
      cholinergic agonist carbachol altered the circadian rhythm of SCN neuronal
      activity in a pattern closely resembling that for analogs of cGMP; nocturnal
      gating of clock sensitivity of each is preserved in vitro. Specific inhibitors of
      guanylyl cyclase (GC) and cGMP-dependent protein kinase (PKG), key elements in
      the cGMP signal transduction cascade, blocked phase shifts induced by carbachol.
      Further, carbachol administration to the SCN at night increased cGMP production
      and PKG activity. The carbachol-induced increase in cGMP was blocked both by
      atropine, an mAChR antagonist, and by LY83583, a GC inhibitor. We conclude that
      (1) mAChR regulation of the SCN is mediated via GC-->cGMP-->PKG, (2) nocturnal
      gating of this pathway is controlled by the circadian clock, and (3) a gating
      site is positioned downstream from cGMP. This study is among the first to
      identify a functional context for mAChR-cGMP coupling in the CNS.

PMID- 8987789
TI  - Resetting the biological clock: mediation of nocturnal CREB phosphorylation via
      light, glutamate, and nitric oxide.
AB  - Synchronization between the environmental lighting cycle and the biological clock
      in the suprachiasmatic nucleus (SCN) is correlated with phosphorylation of the
      Ca2+/cAMP response element binding protein (CREB) at the transcriptional
      activating site Ser133. Mechanisms mediating the formation of phospho-CREB (P
      CREB) and their relation to clock resetting are unknown. To address these issues,
      we probed the signaling pathway between light and P-CREB. Nocturnal light rapidly
      and transiently induced P-CREB-like immunoreactivity (P-CREB-lir) in the rat SCN.
      Glutamate (Glu) or nitric oxide (NO) donor administration in vitro also induced P
      CREB-lir in SCN neurons only during subjective night. Clock-controlled
      sensitivity to phase resetting by light. Glu, and NO is similarly restricted to
      subjective night. The effects of NMDA and nitric oxide synthase (NOS) antagonists
      on Glu-mediated induction of P-CREB-lir paralleled their inhibition of phase
      shifting. Significantly, among neurons in which P-CREB-lir was induced by light
      were NADPH-diaphorase-positive neurons of the SCN's retinorecipient area. Glu
      treatment increased the intensity of a 43 kDa band recognized by anti-P-CREB
      antibodies in subjective night but not day, whereas anti-alpha CREB-lir of this
      band remained constant between night and day. Inhibition of NOS during Glu
      stimulation diminished the anti-P-CREB-lir of this 43 kDa band. Together, these
      data couple nocturnal light, Glu, NMDA receptor activation and NO signaling to
      CREB phosphorylation in the transduction of brief environmental light stimulation
      of the retina into molecular changes in the SCN resulting in phase resetting of
      the biological clock.

PMID- 8987790
TI  - Temporal and spatial expression patterns of transgenes containing increasing
      amounts of the Drosophila clock gene period and a lacZ reporter: mapping elements
      of the PER protein involved in circadian cycling.
AB  - Rhythmic oscillations of the PER protein, the product of the Drosophila period
      (per) gene, in brain neurons of the adult fly are strongly involved in the
      control of circadian rhythms. We analyzed temporal and spatial expression
      patterns of three per-reporter fusion genes, which share the same 4 kb regulatory
      upstream region but contain increasing amounts of per's coding region fused in
      frame to the bacterial lacZ gene. The fusion proteins contained either the N
      terminal half (SG), the N-terminal-two-thirds (BG), or nearly all (XLG) of the
      PER protein. All constructs led to reporter signals only in the known per
      expressing cell types within the anterior CNS and PNS. Whereas the staining
      intensity of SG files was constantly high at different Zeitgeber times, the in
      situ signals in BG and XLG files cycled with approximately 24 hr periodicity in
      the PER-expressing brain cells in wild-type and per01 loss of function files.
      Despite the rhythmic fusion-gene expression within the relevant neurons of per01
      BG files, their locomotor activity in light/dark cycling conditions and in
      constant darkness was identical to that of per01 controls, uncoupling protein
      cycling from rhythmic behavior. The XLG construct restored weak behavioral
      rhythmicity to (otherwise) per01 files, indicating that the C-terminal third of
      PER (missing in BG) is necessary to fulfill the biological function of this clock
      protein.

PMID- 8987792
TI  - Altered excitability of the crayfish lateral giant escape reflex during agonistic
      encounters.
AB  - The excitability of the lateral giant escape reflex of socially dominant and
      submissive crayfish at rest and during agonistic encounters was studied and
      compared. During agonistic encounters the excitability of the lateral giant
      reflex falls, substantially in subordinates and slightly in dominants, whereas at
      rest excitability seems to be independent of social status. Thus, paradoxically,
      socially dominant animals are more likely to execute lateral giant escape
      reactions during interactions than are subordinates. It is suggested that
      subordinates under threat of attack tend to engage circuitry involved in
      flexible, nonreflex ("voluntary") types of escape not mediated by giant neurons
      and therefore inhibit giant neuron-mediated reflex circuitry that produces
      prompt, but less adaptive, responses. In contrast, dominants go about their
      business, mainly ignoring their conspecifics and relying on reflex escape to
      protect them from unexpected attack. Consistent with this view, escape of
      subordinates during agonistic encounters is mediated by nongiant, not reflex,
      circuitry. These observations and their interpretation suggest a possible
      functional role for recently described social status-dependent serotonergic
      modulation of the lateral giant reflex, which is inhibitory in sign in
      subordinates and facilitatory in dominants.

PMID- 8987791
TI  - Neuronal adaptations to changes in the social dominance status of crayfish.
AB  - The effect of superfused serotonin (5-HT; 50 microns) on the synaptic responses
      of the lateral giant (LG) interneuron in crayfish was found to depend on the
      social status of the animal. In socially isolated animals. 5-HT persistently
      increased the response of LG to sensory nerve shock. After social isolates were
      paired in a small cage, they fought and determined their dominant and subordinate
      status. After 12 d of pairing, 5-HT reversibly inhibited the response of LG in
      the social subordinate and reversibly increased the response of LG in the social
      dominant crayfish. The effect of 5-HT changed approximately linearly from
      response enhancement to inhibition in the new subordinate over the 12 d of
      pairing. If, after 12 d pairing, the subordinate was reisolated for 8 d, the
      response enhancement was restored. If the subordinate, instead, was paired with
      another subordinate and became dominant in this new pair, the inhibitory effect
      of 5-HT changed to an enhancing effect over the next 12 d of pairing. If,
      however, two dominant crayfish were paired and one became subordinate, the
      enhancing effect of 5-HT persisted in the new subordinate even after 38 d
      pairing. These different effects of serotonin result from the action of two or
      more molecular receptors for serotonin. A vertebrate 5-HT, agonist had no effect
      on social isolates but reversibly inhibited the response of LG in both dominant
      and subordinate crayfish. The inhibitory effects of the agonist developed
      approximately linearly over the first 12 d of pairing. A vertebrate 5-HT2 agonist
      persistently increased the response of LG in isolate crayfish and reversibly
      increased the response of the cell in dominant and subordinate crayfish. Finally,
      although neurons that might mediate these effects of superfused 5-HT are unknown,
      one pair of 5-HT-immunoreactive neurons appears to contact the LG axon and
      initial axon segment in each abdominal ganglion in its projection caudally from
      the thorax.

PMID- 8987793
TI  - Learning-dependent synaptic modifications in the cerebellar cortex of the adult
      rat persist for at least four weeks.
AB  - Several experiments have demonstrated increased synapse number within the
      cerebellar cortex in association with motor skill learning but not with motor
      activity alone. The persistence of these synaptic changes in the absence of
      continued training was examined in the present experiment. Adult female rats were
      randomly allocated to either an acrobatic condition (AC) or a motor activity
      condition (MC). The AC animals were trained to traverse a complex series of
      obstacles, and each AC animal was pair-matched with an MC animal that traversed
      an obstacle-free runway. These animals were further assigned to one of three
      training conditions. Animals in the EARLY condition were trained for 10
      consecutive days before being killed, animals in the DELAY, condition received
      the same 10 d of training followed by a 28 d period without training, and animals
      in the CONTINUOUS condition were trained for the entire 38 d. Unbiased
      stereological techniques were used to obtain estimates of the number of synapses
      per Purkinje cell within the cerebellar paramedian lobule. Results showed the AC
      animals to have significantly more synapses per Purkinje cell than the MC animals
      in all three training conditions. There were no differences in the number of
      synapses per Purkinje cell among the EARLY, DELAY, and CONTINUOUS conditions.
      These data demonstrate that both the motor skills and the increases in synapse
      number presumed to support them persist in the absence of continued training.

PMID- 8987794
TI  - Oscillatory gamma-band (30-70 Hz) activity induced by a visual search task in
      humans.
AB  - The coherent representation of an object in the visual system has been suggested
      to be achieved by the synchronization in the gamma-band (30-70 Hz) of a
      distributed neuronal assembly. Here we measure variations of high-frequency
      activity on the human scalp. The experiment is designed to allow the comparison
      of two different perceptions of the same picture. In the first condition, an
      apparently meaningless picture that contained a hidden Dalmatian, a neutral
      stimulus, and a target stimulus (twirled blobs) are presented. After the subject
      has been trained to perceive the hidden dog and its mirror image, the second part
      of the recordings is performed (condition 2). The same neutral stimulus is
      presented, intermixed with the picture of the dog and its mirror image (target
      stimulus). Early (95 msec) phase-locked (or stimulus-locked) gamma-band
      oscillations do not vary with stimulus type but can be subdivided into an
      anterior component (38 Hz) and a posterior component (35 Hz). Nonphase-locked
      gamma-band oscillations appear with a latency jitter around 280 msec after
      stimulus onset and disappear in averaged data. They increase in amplitude in
      response to both target stimuli. They also globally increase in the second
      condition compared with the first one. It is suggested that this gamma-band
      energy increase reflects both bottom-up (binding of elementary features) and top
      down (search for the hidden dog) activation of the same neural assembly coding
      for the Dalmatian. The relationships between high- and low-frequency components
      of the response are discussed, and a possible functional role of each component
      is suggested.

PMID- 8987795
TI  - Multiple receptors involved in peripheral alpha 2, mu, and A1 antinociception,
      tolerance, and withdrawal.
AB  - We examined the interactions among three classes of peripherally-acting
      antinociceptive agents (mu-opioid, alpha 2-adrenergic, and A1-adenosine) in the
      development of tolerance and dependence to their antinociceptive effects.
      Antinociception was determined by assessing the degree of inhibition of
      prostaglandin E2 (PGE2)-induced mechanical hyperalgesia, using the Randall
      Selitto paw-withdrawal test. Tolerance developed within 4 hr to the
      antinociceptive effect of the alpha 2-adrenergic agonist clonidine; dependence
      also occurred at that time, demonstrated as a withdrawal hyperalgesia that was
      precipitated by the alpha 2-receptor antagonist yohimbine. These findings are
      similar to those reported previously for tolerance and dependence to mu and A1
      peripheral antinociception (Aley et al., 1995). Furthermore, cross-tolerance and
      cross-withdrawal between mu, A1, and alpha 2 agonists occurred. The observations
      of cross-tolerance and cross-withdrawal suggest that all three receptors are
      located on the same primary afferent nociceptors. In addition, the observations
      suggest that the mechanisms of tolerance and dependence to the antinociceptive
      effects of mu, A1, and alpha 2 are mediated by a common mechanism. Although any
      of the agonists administered alone produce antinociception, we found that mu, A1,
      and alpha 2 receptors may not act independently to produce antinociception, but
      rather may require the physical presence of the other receptors to produce
      antinociception by any one agonist. This was suggested by the finding that
      clonidine (alpha 2-agonist) antinociception was blocked not only by yohimbine
      (alpha 2-antagonist) but also by PACPX (A1-antagonist) and by naloxone (mu
      antagonist), and that DAMGO (mu-agonist) antinociception and CPA (A1-agonist)
      antinociception were blocked not only by naloxone (mu-antagonist) and PACPX (A1
      antagonist), respectively, but also by yohimbine (alpha 2-antagonist). This cross
      antagonism of antinociception occurred at the ID50 dose for each antagonist at
      its homologous receptor. To test the hypothesis that the physical presence of mu
      opioid receptor is required not only for mu antinociception but also for alpha 2
      antinociception, antisense oligodeoxynucleotides (ODNs) for the mu-opioid and
      alpha 2C-adrenergic receptors were administered intrathecally to reduce the
      expression of these receptors on primary afferent neurons. These studies
      demonstrated that mu-opioid ODN administration decreased not only mu-opioid but
      also alpha 2-adrenergic antinociception; A1 antinociception was unaffected. In
      contrast, alpha 2C-adrenergic ODN decreased antinociception induced by all three
      classes of antinociceptive agents. In conclusion, these data suggest that
      peripheral antinociception induced by mu, alpha 2, and A1 agonists requires the
      physical presence of multiple receptors. We propose that there is a mu, A1, alpha
      2 receptor complex mediating antinociception in the periphery. In addition, there
      is cross-tolerance and cross-dependence between mu, A1, and alpha 2
      antinociception, suggesting that their underlying mechanisms are related.

PMID- 8987796
TI  - Quantitative trait loci affecting methamphetamine responses in BXD recombinant
      inbred mouse strains.
AB  - Individual differences in most behavioral and pharmacological responses to abused
      drugs are dependent on both genetic and environmental factors. The genetic
      influences on the complex phenotypes related to drug abuse have been difficult to
      study using classical genetic analyses. Quantitative trait locus (QTL) mapping is
      a method that has been used successfully to examine genetic contributions to some
      of these traits by correlating allelic variation in polymorphic genetic markers
      of known chromosomal location with variation in drug-response phenotypes. We
      evaluated several behavioral responses to multiple doses of methamphetamine
      (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI)
      strains. Stereotyped chewing, horizontal home cage activity, and changes in body
      temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing
      behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH
      sensitivity and allelic status at multiple microsatellite genetic markers were
      subsequently determined for each response. QTLs were provisionally identified for
      each phenotype, some unique to a particular behavior and others that appeared to
      influence multiple phenotypes. Candidate genes suggested by these analyses
      included several that mapped near genes relevant for the neurotransmitters
      acetylcholine and glutamate. The locations of QTLs provisionally identified by
      this analysis were compared with QTLs hypothesized in other studies to influence
      methamphetamine- and cocaine-related phenotypes. In several instances, QTLs
      appeared to overlap, which is consistent with idea that common neural substrates
      underlie some responses to psychostimulants.

PMID- 8987797
TI  - A developmental gene (Tolloid/BMP-1) is regulated in Aplysia neurons by
      treatments that induce long-term sensitization.
AB  - Long-term sensitization training, or procedures that mimic the training, produces
      long-term facilitation of sensory-motor neuron synapses in Aplysia. The long-term
      effects of these procedures require mRNA and protein synthesis (Montarolo et al.,
      1986; Castellucci et al., 1989). Using the techniques of differential display
      reverse transcription PCR (DDRT-PCR) and ribonuclease protection assays (RPA), we
      identified a cDNA whose mRNA level was increased significantly in sensory neurons
      by treatments of isolated pleural-pedal ganglia with serotonin for 1.5 hr or by
      long-term behavioral training of Aplysia. The effects of serotonin and behavioral
      training on this mRNA were mimicked by treatments that elevate cAMP. The aplysia
      mRNA increased by serotonin and behavioral training was 41-45% identical to a
      developmentally regulated gene family which includes Drosophila tolloid and human
      bone morphogenetic protein-1 (BMP-1). Both tolloid and BMP-1 encode
      metalloproteases that might activate TGF-beta (transforming growth factor beta)
      like molecules or process procollagens. Aplysia tolloid/BMP-1-like protein (apTBL
      1) might regulate the morphology and efficacy of synaptic connections between
      sensory and motor neurons, which are associated with long-term sensitization.

PMID- 8987798
TI  - Consequences of nigrostriatal denervation on the functioning of the basal ganglia
      in human and nonhuman primates: an in situ hybridization study of cytochrome
      oxidase subunit I mRNA.
AB  - To examine the consequences of nigrostriatal denervation and chronic levodopa (L
      DOPA) treatment on functional activity of the basal ganglia, we analyzed, using
      in situ hybridization, the cellular expression of the mRNA encoding for
      cytochrome oxidase subunit I (COI mRNA), a molecular marker for functional
      neuronal activity, in the basal ganglia. This analysis was performed in monkeys
      rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      Intoxication, some of which had been receiving L-DOPA, and in patients with
      Parkinson's disease (PD). In MPTP-intoxicated monkeys compared with control
      animals, COI mRNA expression was increased in the subthalamic nucleus (STN) and
      in the output nuclei of the basal ganglia, i.e., the internal segment of the
      globus pallidus and the substantia nigra pars reticulata. This increase was
      partially reversed by L-DOPA treatment. COI mRNA expression remained unchanged in
      the external segment of the globus pallidus (GPe). In PD patients, all of whom
      had been treated chronically by L-DOPA, COI mRNA expression in the analyzed basal
      ganglia structures was similar to that in control subjects. These results are in
      agreement with the accepted model of basal ganglia organization, to the extent
      that the output nuclei of the basal ganglia are considered to be overactive after
      nigrostriatal denervation, partly because of increased activity of excitatory
      afferents from the STN. Yet, our results would also seem to contradict this
      model, because the overactivity of the STN does not seem to be attributable to a
      hypoactivation of the GPe.

PMID- 8987799
TI  - Pontine nitric oxide modulates acetylcholine release, rapid eye movement sleep
      generation, and respiratory rate.
AB  - Pontine cholinergic neurotransmission is known to play a key role in the
      regulation of rapid eye movement (REM) sleep and to contribute to state-dependent
      respiratory depression. Nitric oxide (NO) has been shown to alter the release of
      acetylcholine (ACh) in a number of brain regions, and previous studies indicate
      that NO may participate in the modulation of sleep/wake states. The present
      investigation tested the hypothesis that inhibition of NO synthase (NOS) within
      the medial pontine reticular formation (mPRF) of the unanesthetized cat would
      decrease ACh release, inhibit REM sleep, and prevent cholinergically mediated
      respiratory depression. Local NOS inhibition by microdialysis delivery of N(G)
      nitro-L-arginine (NLA) significantly reduced ACh release in the cholinergic cell
      body region of the pedunculopontine tegmental nucleus and in the cholinoceptive
      mPRF. A second series of experiments demonstrated that mPRF microinjection of NLA
      significantly reduced the amount of REM sleep and the REM sleep-like state caused
      by mPRF injection of the acetylcholinesterase inhibitor neostigmine. Duration but
      not frequency of REM sleep epochs was significantly decreased by mPRF NLA
      administration. Injection of NLA into the mPRF before neostigmine injection also
      blocked the ability of neostigmine to decrease respiratory rate during the REM
      sleep-like state. Taken together, these findings suggest that mPRF NO contributes
      to the modulation of ACh release, REM sleep, and breathing.

PMID- 8987800
TI  - The neuronal basis of the behavioral choice between swimming and shortening in
      the leech: control is not selectively exercised at higher circuit levels.
AB  - Swimming and the whole-body shortening reflex are two incompatible behaviors
      performed by the medicinal leech Hirudo medicinalis. We set out to examine the
      neuronal basis of the choice between these behaviors, taking advantage of the
      fact that the neuronal circuit underlying swimming is relatively well understood.
      The leech swim circuit is organized hierarchically and contains three
      interneuronal levels, including two upper levels of "command-like" neurons. We
      tested the responses of the swim circuit neurons to stimuli that produced
      shortening, using reduced preparations in which neurophysiological recording
      could be performed while behaviors were elicited. We found that the majority of
      the swim circuit neurons, including most of the command-like cells and all of the
      cells at the highest hierarchical level of the circuit, were excited by stimuli
      that produced shortening as well as by stimuli that produced swimming. Only a
      subset of neurons, at levels below the top, were inhibited during shortening;
      these included one of the command-like cells and an oscillator cell (an
      interneuron that is part of the central pattern generator for swimming). These
      results imply that the control of the choice between swimming and shortening is
      not exercised selectively at the higher levels of the swim circuit.

PMID- 8987801
TI  - Increased probability of GABA release during withdrawal from morphine.
AB  - Opioid receptors located on interneurons in the ventral tegmental area (VTA)
      inhibit GABA(A)-mediated synaptic transmission to dopamine projection neurons.
      The resulting disinhibition of dopamine cells in the VTA is thought to play a
      pivotal role in drug abuse; however, little is known about how this GABAA synapse
      is affected after chronic morphine treatment. The regulation of GABA release
      during acute withdrawal from morphine was studied in slices from animals treated
      for 6-7 d with morphine. Slices containing the VTA were prepared and maintained
      in morphine-free solutions, and GABAA IPSCs were recorded from dopamine cells.
      The amplitude of evoked IPSCs and the frequency of spontaneous miniature IPSCs
      measured in slices from morphine-treated guinea pigs were greater than placebo
      treated controls. In addition, activation of adenylyl cyclase, with forskolin,
      and cAMP-dependent protein kinase, with Sp-cAMPS, caused a larger increase in
      IPSCs in slices from morphine-treated animals. Conversely, the kinase inhibitors
      staurosporine and Rp-CPT-cAMPS decreased GABA IPSCs to a greater extent after
      drug treatment. The results indicate that the probability of GABA release was
      increased during withdrawal from chronic morphine treatment and that this effect
      resulted from an upregulation of the cAMP-dependent cascade. Increased
      transmitter release from opioid-sensitive synapses during acute withdrawal may be
      one adaptive mechanism that results from prolonged morphine treatment.

PMID- 8987802
TI  - Detection and discrimination of first- and second-order motion in patients with
      unilateral brain damage.
AB  - The present investigation explored the extent to which extrastriate cortex is
      necessary for various aspects of motion processing and whether the processing of
      first-order (Fourier) and second-order (non-Fourier) motion involves the same
      extrastriate cortical regions. Orientation, direction, and speed discrimination
      thresholds were measured in 21 patients with unilateral damage to the lateral
      occipital, temporal, or posterior parietal cortex. Their results were compared
      with those of 14 age-matched control subjects. The stimuli were static random-dot
      noise patterns, the luminance of which (first-order) or contrast (second-order)
      was modulated by a drifting sinusoid. Each image was presented at an eccentricity
      of 5.6 deg in one of the four visual quadrants. The contrasts required to
      identify orientation and direction were measured in a forced-choice paradigm for
      three speeds (1.5, 3, and 6 deg/sec). Speed discrimination performance was
      measured for stimuli presented simultaneously in two of the four quadrants. The
      results indicate the following: (1) orientation thresholds were increased only
      slightly in the patients; (2) direction thresholds were modestly elevated, and
      this effect was more pronounced for second-order stimuli than for first-order
      stimuli; (3) speed discrimination thresholds were elevated significantly in the
      patients with lesions in the region bordering superior-temporal and lateral
      occipital cortex; and (4) speed discrimination thresholds for first-order stimuli
      were more elevated than those for second-order stimuli. The results suggest that
      there is substantial overlap in the cortical areas involved in first- and second
      order speed discrimination.

PMID- 8987803
TI  - Cellular, subcellular, and subsynaptic distribution of AMPA-type glutamate
      receptor subunits in the neostriatum of the rat.
AB  - Glutamate released in the basal ganglia is involved in the expression of clinical
      symptoms of neurodegenerative diseases like Parkinson's or Huntington's.
      Neostriatal neurons are the targets of glutamatergic inputs derived from the
      cortex and the thalamus acting via AMPA-type as well as other glutamate
      receptors. To determine the location of subunits of the AMPA subclass of
      glutamate receptors (GluR) in the rat neostriatum, we applied multiple
      immunocytochemical techniques using anti-peptide antibodies against the GluR1,
      GluR2/3, and GluR4 subunits at both the light and electron microscopic levels.
      All medium spiny efferent neurons, some of which were identified as striatonigral
      neurons, displayed immunoreactivity for GluR1 and GluR2/3 subunits. Double
      immunofluorescence revealed that at least 70-90% of parvalbumin-immunopositive
      GABAergic interneurons were immunoreactive for each of GluR1, GluR2/3, or GluR4
      subunits and that at least 40% of choline acetyltransferase-immunopositive
      cholinergic interneurons were immunopositive for GluR1 or GluR4 subunits. The
      majority of nitric oxide synthase-immunopositive neurons had no detectable
      immunoreactivity for any of the AMPA receptor subunits. Electron microscopic
      analysis confirmed the presence of immunoreactivity for GluR1 and GluR2/3 in the
      perikarya of spiny neurons and interneurons and GluR4 in perikarya of
      interneurons only. GluR1 and GluR2/3 subunits were detected in dendrites and
      spines. A significant population of extrasynaptic receptors was revealed by pre
      embedding immunogold labeling along the plasma membranes of perikarya, dendrites,
      and spines. Receptors were concentrated in the postsynaptic membrane
      specialization of asymmetrical synapses, as revealed by the postembedding
      immunogold method. Quantitative analysis demonstrated that immunoreactivity for
      the GluR1 and GluR2/3 subunits is higher at the periphery than at the middle of
      the postsynaptic membrane specialization. Our results demonstrate that AMPA
      receptor subunits are distributed widely and heterogeneously among striatal
      neurons and are concentrated on the postsynaptic membrane of asymmetrical
      synaptic specializations, although extrasynaptic receptors are also present.

PMID- 8987804
TI  - Differential localization of delta glutamate receptors in the rat cerebellum:
      coexpression with AMPA receptors in parallel fiber-spine synapses and absence
      from climbing fiber-spine synapses.
AB  - The delta 2 glutamate receptors are prominently expressed in Purkinje cells and
      are thought to play a key role in the induction of cerebellar long-term
      depression. The synaptic and subsynaptic localization of delta receptors in rat
      cerebellar cortex was investigated with sensitive and high-resolution immunogold
      procedures. After postembedding incubation with an antibody raised to a C
      terminal peptide of delta 2, high gold particle densities occurred in all
      parallel fiber synapses with Purkinje cell dendritic spines, whereas other
      synapses were consistently devoid of labeling. Among the types of immunonegative
      synapse were climbing fiber synapses with spines and parallel fiber synapses with
      dendritic stems of interneurons. At the parallel fiber-spine synapse, gold
      particles signaling delta receptors were restricted to the postsynaptic
      specialization. By the use of double labeling with two different gold particle
      sizes, it was shown that delta and AMPA GluR2/3 receptors were colocalized along
      the entire extent of the postsynaptic specialization without forming separate
      domains. The distribution of gold particles representing delta receptors was
      consistent with a cytoplasmic localization of the C terminus and an absence of a
      significant presynaptic pool of receptor molecules. The present data suggest that
      the delta 2 receptors are targeted selectively to a subset of Purkinje cell
      spines and that they are coexpressed with ionotropic receptors in the
      postsynaptic specialization. This arrangement could allow for a direct
      interaction between the two classes of receptor.

PMID- 8987805
TI  - Decreased [18F]spiperone binding in putamen in idiopathic focal dystonia.
AB  - In this study we have investigated the pathophysiology of two idiopathic focal
      dystonias: hand cramp with excessive cocontractions of agonist and antagonist
      hand or forearm muscles during specific tasks, such as writing, and facial
      dystonia manifested by involuntary eyelid spasms (blepharospasm) and lower facial
      and jaw spasms (oromandibular dystonia). We used positron emission tomography
      (PET) to measure the in vivo binding of the dopaminergic radioligand
      [18F]spiperone in putamen in 21 patients with these two focal dystonias and
      compared the findings with those from 13 normals. We measured regional cerebral
      blood flow and blood volume in each subject as well as the radiolabeled
      metabolites of [18F]spiperone in arterial blood. A stereotactic method of
      localization, independent of the appearance of the images, was used to identify
      the putamen in all of the PET images. We analyzed the PET and arterial blood data
      with a validated nonsteady-state tracer kinetic model representing the in vivo
      behavior of the radioligand. An index of binding called the combined forward rate
      constant was decreased by 29% in dystonics, as compared with normals (p < 0.05).
      There were no significant differences between dystonics and normals in regional
      blood flow, blood volume, nonspecific binding, permeability-surface area product
      of [18F]spiperone or the dissociation rate constant. These findings are
      consistent with a decrease of dopamine D2-like binding in putamen and are the
      first demonstration of a receptor abnormality in idiopathic dystonia. These
      results have important implications for the pathophysiology of dystonia as well
      as for function of the basal ganglia.

PMID- 8987806
TI  - Differential influence of associative and nonassociative learning mechanisms on
      the responsiveness of prefrontal and accumbal dopamine transmission to food
      stimuli in rats fed ad libitum.
AB  - Feeding a novel food (Fonzies) to rats fed ad libitum with standard food
      increased extracellular dopamine (DA) in the medial prefrontal cortex (PFCX) and
      in the medial nucleus accumbens (NAc). Previous Fonzies feeding, although it did
      not affect the increase of extracellular DA in the PFCX in response to Fonzies
      feeding, blunted that increase in the NAc (habituation); recovery from
      habituation in the NAc was complete 5 d after previous Fonzies feeding.
      Predictive association of an otherwise neutral stimulus extrinsic to Fonzies
      (empty plastic box) with Fonzies feeding resulted in the acquisition by the
      stimulus of the property to elicit incentive responses directed toward the
      stimulus and to increase extracellular DA in the PFCX. However, the same
      stimulus, or a more complex stimulus including intrinsic stimuli (Fonzies-filled
      plastic box), failed to acquire the ability to modify extracellular DA in the
      NAc. Pseudoconditioning, i.e., nonpredictive association of the extrinsic
      stimulus (empty box) with Fonzies feeding, did not result in acquisition by the
      stimulus of the property to elicit incentive responses and to increase
      extracellular DA in the PFCX. Repeated nonreinforced presentation of previously
      conditioned extrinsic stimuli (empty box) resulted in extinction of the property
      to elicit incentive responses and to increase extracellular DA in the PFCX. These
      results indicate that in rats fed ad libitum, phasic activation of mesocortical
      and mesolimbic DA systems by motivational stimuli is differentially influenced by
      associative (conditioning) and nonassociative (habituation) learning mechanisms
      and is differentially related to acquisition and expression of incentive
      motivation.

PMID- 8987807
TI  - GABAergic presubicular projections to the medial entorhinal cortex of the rat.
AB  - We characterized presubicular neurons giving rise to bilateral projections to the
      medial entorhinal cortex (MEA) of the rat. Retrograde labeling of presubiculo
      entorhinal projections with horseradish peroxidase and subsequent GABA
      immunocytochemistry revealed that 20-30% of the ipsilaterally projecting neurons
      are GABAergic. No GABAergic projections to the contralateral MEA were observed.
      GABAergic projection neurons were observed only in the dorsal part of the
      presubiculum, which, when taking into account the topography of presubicular
      projections to MEA, indicates that only the dorsal part of MEA receives GABAergic
      input. The GABAergic projection neurons constitute approximately 30-40% of all
      GABAergic neurons present in the superficial layers of the dorsal presubiculum.
      Using double-label fluorescent retrograde tracing, we found that the ipsilateral
      and contralateral presubiculo-entorhinal projections originate from different
      populations of neurons. Anterograde labeling of presubiculo-entorhinal
      projections and electron microscopical analysis of labeled terminals
      substantiated the presence of a restricted GABAergic presubiculo-entorhinal
      projection. A small fraction of afferents to only ipsilateral dorsal MEA formed
      symmetrical synapses with dendritic shafts. No symmetrical synapses on spines
      were noted. Most afferents to the dorsal part of ipsilateral MEA, as well as all
      afferents to the remaining ipsilateral and contralateral MEA, formed asymmetrical
      synapses with both spines and dendritic shafts in an almost equal ratio. Thus, we
      conclude that the majority of the presubiculo-entorhinal projections exert an
      excitatory effect on both principal neurons and interneurons. The projections
      from the dorsal part of the presubiculum comprise a small inhibitory component
      that originates from GABAergic neurons and targets entorhinal interneurons.

PMID- 8987808
TI  - Release of [3H]-D-aspartate from primary astrocyte cultures in response to raised
      external potassium.
AB  - There are significant Ca2+-independent increases in extracellular glutamate and
      aspartate during various CNS insults such as ischemia and anoxia. However, the
      cellular sources of such presumed nonvesicular excitatory amino acid (EAA)
      release have not been established. To further explore potential mechanisms and
      sites for EAA release, we studied the release of preloaded [3H]-D-aspartate from
      primary cultured astrocytes prepared from the cerebral cortices of rat pups. Two
      phases of release were seen in response to raised KCl. The first phase was small
      and transient, and the second phase was slower and increased progressively. The
      initial phase of [3H]-D-aspartate release was greatly enhanced by ouabain
      pretreatment and was inhibited when astrocytes were preexposed to the EAA
      transport inhibitor threo-hydroxy beta-aspartic acid (THBA). Neither of these
      manipulations affected the second release component. The second phase of release
      was inhibited by an anion channel blocker, L-644,711, which is known to inhibit
      hypotonic swelling-induced release of EAA. Ouabain also resulted in the first
      phase of release occurring at lower [K+]o. Omission of Ca2+ had no effect on
      either phase of [3H]-D-aspartate release. These results support the hypothesis
      that the first component of release in cultured astrocytes is a reversal of the
      glutamate transporter, and the second component is a result of high KCl-induced
      swelling. Because marked increases in [K+]o are well established in CNS
      pathologies such as ischemia, such release may represent a significant source for
      the increased extracellular EAAs seen in such conditions.

PMID- 8987809
TI  - Translocation of RNA granules in living neurons.
AB  - Sorting of RNAs to specific subcellular loci occurs in diverse settings from fly
      oocytes to mammalian neurons. Using the membrane-permeable nucleic acid stain
      SYTO 14, we directly visualized the translocation of endogenous RNA in living
      cells. Labeled RNA was distributed nonrandomly as discrete granules in neuronal
      processes. The labeled granules colocalized with poly(A+) mRNA, with the 60S
      ribosomal subunit, and with elongation factor 1alpha, suggesting that granules
      represent a translational unit. A subset of labeled granules colocalized with
      beta-actin mRNA. Correlative light and electron microscopy indicated that the
      fluorescent granules corresponded to clusters of ribosomes at the ultrastructural
      level. Poststaining of sections with heavy metals confirmed the presence of
      ribosomes within these granules. In living neurons, a subpopulation of RNA
      granules was motile during the observation period. They moved at an average rate
      of 0.1 microm/sec. In young cultures their movements were exclusively
      anterograde, but after 7 d in culture, one-half of the motile granules moved in
      the retrograde direction. Granules in neurites were delocalized after treatment
      with microtubule-disrupting drugs. These results raise the possibility of a
      cellular trafficking system for the targeting of RNA in neurons.

PMID- 8987810
TI  - STEP61: a member of a family of brain-enriched PTPs is localized to the
      endoplasmic reticulum.
AB  - The STEP family of protein tyrosine phosphatases is highly enriched within the
      CNS. Members of this family are alternatively spliced to produce both
      transmembrane and cytosolic variants. This manuscript describes the distinctive
      intracellular distribution and enzymatic activity of the membrane-associated
      isoform STEP61. Transfection experiments in fibroblasts, as well as subcellular
      fractionations, sucrose density gradients, immunocytochemical labeling, and
      electron microscopy in brain tissue, show that STEP61 is an intrinsic membrane
      protein of striatal neurons and is associated with the endoplasmic reticulum. In
      addition, structural analysis of the novel N-terminal region of STEP61 reveals
      several motifs not present in the cytosolic variant STEP46. These include two
      putative transmembrane domains, two sequences rich in Pro, Glu, Asp, Ser, and Thr
      (PEST sequences), and two polyproline-rich domains. Like STEP46, STEP61 is
      enriched in the brain, but the recombinant protein has less enzymatic activity
      than STEP46. Because STEP46 is contained in its entirety within STEP61 and
      differs only in the extended N terminus of STEP61, this amino acid sequence is
      responsible for the association of STEP61 with membrane compartments and may also
      regulate its enzymatic activity.

PMID- 8987811
TI  - Thyroid hormone-responsive genes in developing cerebellum include a novel
      synaptotagmin and a hairless homolog.
AB  - Proper development of the mammalian CNS requires sufficient thyroid hormone;
      thyroid hormone deficiency during a brief perinatal period produces severe
      neurological defects in humans and experimental animals. Thyroid hormone exerts
      its effects through nuclear receptors, which modulate the transcription of
      downstream genes in response to hormone binding. Surprisingly, few genes that are
      regulated by thyroid hormone receptors in the CNS have been described. Here, I
      report the isolation and characterization of genes that are expressed in response
      to thyroid hormone in developing rat brain. One such gene (Srg1) encodes a novel
      protein related to synaptotagmin, a protein involved in regulating
      neurotransmitter release; another (hr) encodes a putative zinc finger protein
      related to the product of a recently identified mouse gene, hairless. Both Srg1
      and hr are induced rapidly (<4 hr), suggesting that they are regulated directly
      by thyroid hormone. The temporal and spatial expression of both Srg1 and hr is
      characteristic of genes important to nervous system development. Srg1 and hr are
      likely part of a cascade of gene activation induced by thyroid hormone that is
      critical for CNS organization and development.

PMID- 8987812
TI  - Immunocytological and biochemical localization and biological activity of the
      newly sequenced cerebral peptide 2 in Aplysia.
AB  - Cerebral peptide 2 (CP2), a 41 amino acid neuropeptide, was identified because it
      was transported from the cerebral ganglia of Aplysia to other central ganglia.
      Immunocytology indicates that CP2 is distributed widely in the CNS and peripheral
      tissues of Aplysia. Most CP2-immunoreactive neurons were found in the cerebral
      ganglia and extensively overlap with the distribution of cerebral peptide 1
      (CP1). HPLC analyses confirm that individual cerebral neurons synthesize both CP1
      and CP2. In other ganglia, CP1 and CP2 are localized predominantly to different
      neurons. CP2-immunoreactive fibers and varicosities are present in the neuropil
      of all ganglia but were found surrounding cell bodies and axon hillocks most
      often in the buccal and abdominal ganglia. Thus, the effects of CP2 on neurons in
      these ganglia were determined using intracellular recording. In the buccal
      ganglia, CP2 evokes rhythmic activity in many motor neurons that seems similar to
      that observed during ingestion; however, only one identified neuron was found to
      be depolarized directly. By contrast, in the abdominal ganglion, many neurons are
      depolarized directly by CP2. A number of these have been shown to be part of the
      circuit that regulates respiratory pumping. Injection of CP2 into freely behaving
      Aplysia increases the rate of respiratory pumping and causes other changes in
      behavior. CP2 is stable in hemolymph, which raises the possibility that it may
      act as a hormone. Thus, CP2 is a bioactive neuropeptide that is present in many
      neurons and likely functions as a transmitter or a hormone.

PMID- 8987813
TI  - Polygenic disease and retinitis pigmentosa: albinism exacerbates photoreceptor
      degeneration induced by the expression of a mutant opsin in transgenic mice.
AB  - Expression of a mouse opsin transgene containing three point mutations (V20G,
      P23H, and P27L; termed VPP) causes a progressive photoreceptor degeneration that
      resembles in many important respects that seen in patients with autosomal
      dominant retinitis pigmentosa caused by a P23H point mutation. We have attempted
      to determine whether the degree of degeneration induced by expression of the
      transgene is influenced by albinism, a genetically mediated recessive trait that
      results in a deficiency in melanin formation in pigmented tissues throughout the
      body. Litters of albino and pigmented mice (normal as well as transgenic) were
      reared in either darkness or cyclic light. Retinal structure and function were
      evaluated by light microscopy, electroretinography (ERG), and retinal
      densitometry. The data were consistent in demonstrating that at similar ages, the
      extent of photoreceptor degeneration was greater in transgenic albino animals
      than in their pigmented counterparts. The albino VPP mice had significantly fewer
      cell bodies in the outer nuclear layer of the retina, a larger reduction in ERG
      amplitude, and a lower rhodopsin content in the rod photoreceptors. These
      structural and functional differences could not be attributed to the greater
      level of retinal illumination experienced by the albino retina under normal
      ambient conditions, because they persisted when pigmented and albino mice were
      reared in darkness from birth. Although the explanation remains unclear, our
      findings indicate that the rate of photoreceptor degeneration in VPP mice is
      adversely affected by the existence of the albino phenotype, a factor that may
      have implications for the counseling of human patients with retinitis pigmentosa
      and a familial history of other genetic disorders.

PMID- 8987814
TI  - Motor discoordination results from combined gene disruption of the NMDA receptor
      NR2A and NR2C subunits, but not from single disruption of the NR2A or NR2C
      subunit.
AB  - NMDA receptors consist of two distinct classes of subunits. The NR1 subunit
      possesses all properties of the NMDA receptor-channel complex, whereas four NR2
      subunits (NR2A-2D) potentiate and differentiate NMDA receptor responses by
      heteromeric assemblies with NR1. The mRNAs for the five NMDA receptor subunits
      are expressed in the cerebellum in a distinct temporospatial manner. To study
      functions of the NMDA receptors in the cerebellum, we generated knockout mice
      deficient in either NR2A or NR2C or both of these subunits. All three mutant mice
      developed normally and showed normal overall morphology of the cerebellum. The
      NMDA receptor-mediated components of EPSCs in granule cells, as assessed by whole
      cell recordings of cerebellar slices, were reduced in NR2A- and NR2C-deficient
      mice and nearly abolished in mice lacking both NR2A and NR2C. The NR2A- and NR2C
      deficient granule cells were different in the current-voltage relationship and
      time course of NMDA receptor responses. The NR2A and NR2C subunits thus
      contribute to distinct NMDA receptor-mediated excitatory transmission in mossy
      fiber-granule cell synapses in the mature cerebellum. Both NR2A- and NR2C
      deficient mice showed no impaired movements in the motor coordination tasks
      tested. The mutant mice deficient in both NR2A and NR2C could also manage simple
      coordinated tasks, such as staying on a stationary or a slowly rotating rod, but
      failed more challenging tasks such as staying on a quickly rotating rod. These
      data demonstrate that the NMDA receptors play an active role in motor
      coordination.

PMID- 8987815
TI  - A Drosophila calcium channel alpha1 subunit gene maps to a genetic locus
      associated with behavioral and visual defects.
AB  - We have cloned cDNAs that encode a complete open reading frame for a calcium
      channel alpha1 subunit from Drosophila melanogaster. The deduced 1851 amino acid
      protein belongs to the superfamily of voltage-gated sodium and calcium channels.
      Phylogenetic analysis shows that the sequence of this subunit is relatively
      distant from sodium channel alpha subunits and most similar to genes encoding the
      A, B, and E isoforms of calcium channel alpha1 subunits. To indicate its
      similarity to this subfamily of vertebrate isoforms, we name this protein Dmca1A,
      for Drosophila melanogaster calcium channel alpha1 subunit, type A. Northern blot
      analysis detected a single 10. 5 kb transcript class that is regulated
      developmentally, with expression peaks in the first larval instar, midpupal, and
      late pupal stages. In late-stage embryos, Dmca1A is expressed preferentially in
      the nervous system. Variant transcripts are generated by alternative splicing. In
      addition, single nucleotide variations between cDNAs and genomic sequence are
      consistent with RNA editing. Dmca1A maps to a chromosomal region implicated in,
      and is the likely candidate for, the gene involved in the generation of
      behavioral, physiological, and lethal phenotypes of the cacophony, nightblind-A,
      and lethal(1)L13 mutants.

PMID- 8987816
TI  - Human alpha4beta2 neuronal nicotinic acetylcholine receptor in HEK 293 cells: A
      patch-clamp study.
AB  - The cloning and expression of genes encoding for the human neuronal nicotinic
      acetylcholine receptors (nAChRs) has opened new possibilities for investigating
      their physiological and pharmacological properties. Cells (HEK 293) stably
      transfected with two of the major brain subunits, alpha4 and beta2, were
      characterized electrophysiologically using the patch-clamp technique. Fast
      application of the natural ligand ACh can evoke currents up to 3500 pA, with an
      apparent affinity (EC50) of 3 microM and a Hill coefficient of 1.2. The rank
      order of potency of four nAChR ligands to activate human alpha4beta2 receptors is
      (-)-nicotine > ACh > (-)-cytisine > ABT-418. At saturating concentrations, the
      efficacy of these ligands is ABT-418 >> (-)-nicotine > ACh >> (-)-cytisine > GTS
      21 (previously named DMXB). Coapplication of 1 microM ACh with known nAChR
      inhibitors such as dihydro-beta-erythroidine and methyllycaconitine reversibly
      reduces the current evoked by the agonist with respective IC50 values of 80 nM
      and 1.5 microM. The current-voltage relationship of human alpha4beta2 displays a
      strong rectification at positive potentials. Experiments of ionic substitutions
      suggest that human alpha4beta2 nAChRs are permeable to sodium and potassium ions.
      In the "outside-out" configuration, ACh evokes unitary currents (main conductance
      46 pS) characterized by a very fast rundown. Potentiation of the ACh-evoked
      currents is observed when the extracellular calcium concentration is increased
      from 0.2 to 2 mM. In contrast, however, a reduction of the evoked currents is
      observed when calcium concentration is elevated above 2 mM.

PMID- 8987817
TI  - Neuronal nicotinic receptor expression in sensory neurons of the rat trigeminal
      ganglion: demonstration of alpha3beta4, a novel subtype in the mammalian nervous
      system.
AB  - The identification of a family of neuronal nicotinic receptor subunit genes
      establishes the potential for multiple subtypes with diverse physiological
      functions. Virtually all of the high affinity nicotinic receptors measured to
      date in the rodent CNS are composed of alpha4 and beta2 subunits only. However,
      the demonstration of other subunit transcripts in a variety of central and
      peripheral nervous tissues suggests a greater degree of receptor subtype
      heterogeneity than so far has been elucidated. The purpose of the present studies
      was to determine at the mRNA and protein levels which neuronal nicotinic receptor
      subunits are expressed by sensory neurons of the rat trigeminal ganglion and in
      what combinations these gene products associate to form neuronal nicotinic
      receptor subtypes in this tissue. Radioreceptor binding analysis indicated that
      in the adult rat trigeminal ganglion there exist at least two nicotinic receptor
      binding sites with differing affinities for [3H]-epibatidine. In situ
      hybridization histochemical studies revealed the existence of mRNA encoding the
      alpha3, alpha4, alpha5, beta2, and beta4 subunits, but not the alpha2 subunit.
      Immunoprecipitation with subunit-specific antisera demonstrated that each of the
      subunits present in the ganglion at the mRNA level is a constituent of nicotinic
      receptors capable of binding 3H-epibatidine. Various applications of these
      approaches yielded strong evidence that, in addition to alpha4beta2, which is
      thought to be the predominant neuronal nicotinic receptor subtype in the rodent
      CNS, trigeminal sensory neurons express as the principal subtype alpha3beta4,
      which has not been demonstrated previously in mammalian nervous tissue.

PMID- 8987818
TI  - Enhanced cleavage of an atypical intron of dopamine D3-receptor pre-mRNA in
      chronic schizophrenia.
AB  - The D2-class of dopamine receptors (D2, D3, and D4) is a target for typical and
      atypical neuroleptic drugs. They have been considered, therefore, as factors that
      may contribute to the pathophysiology of psychotic disorders. Interestingly, in
      cortical brain tissues obtained postmortem form patients with chronic
      schizophrenia D3 mRNA was found to be significantly lower than in the
      corresponding anatomic regions of controls. Because the expression of a truncated
      D3-like mRNA (named D3nf) appeared to be unaffected in schizophrenic brains,
      these findings suggest the possibility that the loss of D3 mRNA results from an
      abnormal splicing of D3 pre-mRNA in schizophrenia that is accompanied by an
      increased accumulation of the truncated D3nf mRNA. To test this, three approaches
      were taken. (1) Substrate D3 pre-mRNA was spliced in vitro in HeLa nuclear
      extracts. Results from these experiments show that D3nf mRNA results from the
      alternative removal of a short spliceosomal intron in D3 pre-mRNA that has a
      noncanonical 3' splice site. (2) Substrate D3 pre-mRNA was spliced in vivo in
      stably transfected rat GH3 cells. Despite the atypical 3' cleavage that is
      necessary to generate D3nf mRNA, D3 and D3nf mRNA were found to be processed at
      similar amounts. (3) The relative D3/D3nf splicing efficiencies were then
      determined in the anterior cingulate cortex of postmortem brains obtained from
      controls and from patients with chronic schizophrenia. Significant differences
      were found between the relative levels of D3 and D3nf mRNA, suggesting that an
      enhanced D3nf-specific splicing of D3 pre-mRNA in schizophrenia leads to a
      decreased expression of D3 mRNA.

PMID- 8987819
TI  - Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human
      hippocampus and is capable of degrading the amyloid-beta peptide (1-40).
AB  - We reported earlier that the levels of Ca2+-dependent metalloproteinases are
      increased in Alzheimer's disease (AD) specimens, relative to control specimens.
      Here we show that these enzymes are forms of the matrix metalloproteinase MMP-9
      (EC3.4.24. 35) and are expressed in the human hippocampus. Affinity-purified
      antibodies to MMP-9 labeled pyramidal neurons, but not granular neurons or glial
      cells. MMP-9 mRNA is expressed in pyramidal neurons, as determined with
      digoxigenin-labeled MMP-9 riboprobes, and the presence of this mRNA is confirmed
      with reverse transcriptase PCR. The cellular distribution of MMP-9 is altered in
      AD because 76% of the total 100 kDa enzyme activity is found in the soluble
      fraction of control specimens, whereas only 51% is detectable in the same
      fraction from AD specimens. The accumulated 100 kDa enzyme from AD brain is
      latent and can be converted to an active form with aminophenylmercuric acetate.
      MMP-9 also is detected in close proximity to extracellular amyloid plaques.
      Because a major constituent of plaques is the 4 kDa beta-amyloid peptide,
      synthetic Abeta1-40 was incubated with activated MMP-9. The enzyme cleaves the
      peptide at several sites, predominantly at Leu34-Met35 within the membrane
      spanning domain. These results establish that neurons have the capacity to
      synthesize MMP-9, which, on activation, may degrade extracellular substrates such
      as beta-amyloid. Because the latent form of MMP-9 accumulates in AD brain, it is
      hypothesized that the lack of enzyme activation contributes to the accumulation
      of insoluble beta-amyloid peptides in plaques.

PMID- 8987820
TI  - Monoclonal antibody O10 defines a conformationally sensitive cell-surface epitope
      of proteolipid protein (PLP): evidence that PLP misfolding underlies
      dysmyelination in mutant mice.
AB  - Mutations in the gene for proteolipid protein (PLP) have been associated with CNS
      dysmyelination and abnormal oligodendrocyte death in spontaneous mouse mutants
      and in Pelizaeus-Merzbacher disease; however, the effect of mutations on PLP
      structure and function are little understood. We have identified a monoclonal
      antibody directed against a novel cell surface epitope of PLP, termed O10. By
      immunofluorescence analysis, COS-7 cells transiently transfected to express PLP
      (or its isoform DM20) can be stained with antibody O10 and another antibody
      (A431) directed against the C terminus of PLP/DM20. The subcellular distribution
      of immunofluorescence labels for the two antibodies is not identical, suggesting
      that the O10 epitope is acquired post-translationally. When PLP/DM20 from jimpy,
      jimpymsd, and rumpshaker mutant mice is expressed in COS-7 cells and compared
      with wild-type PLP/DM20, none of the mutant isoforms displays the O10 epitope,
      whereas the C-terminal epitope is detected. Because the O10 but not the A431
      epitope is also sensitive to SDS and reducing agents, this strongly suggests
      abnormal protein folding in the PLP mutants. PLP from jimpymsd mice is obviously
      misfolded, because the amino acid substitution (Ala242 --> Val) is located within
      a transmembrane domain to which the O10 antibody does not bind. We propose that
      the O10 epitope emerges as the full length protein reaches a functional tertiary
      structure and that the absence of this epitope marks a structural defect of PLP
      that leads to dysmyelination.

PMID- 8987821
TI  - Cell type-specific sorting of neuropeptides: a mechanism to modulate peptide
      composition of large dense-core vesicles.
AB  - The CNS of Lymnaea stagnalis contains two populations of egg-laying hormone (ELH)
      producing neurons that differ in size and topology. In type I neurons, all
      peptides located C-terminally from the cleavage site Arg-Ser-Arg-Arg180-183 are
      sorted into secretory large dense-core vesicles (LDCV), whereas N-terminal
      located peptides accumulate in a distinct type of vesicle, the large
      electrondense granule (LEG). Via immunoelectron microscopy, we now show that the
      second population of ELH-producing neurons, type II neurons, lack LEG and
      incorporate all proELH-derived peptides into LDCV. This finding provides the
      first example of a cell type-specific sorting of neuropeptides into LDCV.
      Furthermore, we provide evidence that LEG are formed through a differential
      condensation process in the trans-Golgi network and that these bodies are
      ultimately degraded. Analysis of the endoprotease composition of the two types of
      proELH-producing neurons suggests that the formation of LEG, and consequently the
      retention of N-terminal peptides from the secretory pathway, requires the action
      of a furin-like protein.

PMID- 8987822
TI  - Neural cell type-specific expression of QKI proteins is altered in quakingviable
      mutant mice.
AB  - qkI, a newly cloned gene lying immediately proximal to the deletion in the
      quakingviable mutation, is transcribed into three messages of 5, 6, and 7 kb.
      Antibodies raised to the unique carboxy peptides of the resulting QKI proteins
      reveal that, in the nervous system, all three QKI proteins are expressed strongly
      in myelin-forming cells and also in astrocytes. Interestingly, individual
      isoforms show distinct intracellular distributions: QKI-6 and QKI-7 are localized
      to perikaryal cytoplasm, whereas QKI-5 invariably is restricted to the nucleus,
      consistent with the predicted role of QKI as an RNA-binding protein. In
      quakingviable mutants, which display severe dysmyelination, QKI-6 and QKI-7 are
      absent exclusively from myelin-forming cells. By contrast, QKI-5 is absent only
      in oligodendrocytes of severely affected tracts. These observations implicate QKI
      proteins as regulators of myelination and reveal key insights into the mechanisms
      of dysmyelination in the quakingviable mutant.

PMID- 8987823
TI  - Endocytosis of activated TrkA: evidence that nerve growth factor induces
      formation of signaling endosomes.
AB  - The survival, differentiation, and maintenance of responsive neurons are
      regulated by nerve growth factor (NGF), which is secreted by the target and
      interacts with receptors on the axon tip. It is uncertain how the NGF signal is
      communicated retrogradely from distal axons to neuron cell bodies. Retrograde
      transport of activated receptors in endocytic vesicles could convey the signal.
      However, little is known about endocytosis of NGF receptors, and there is no
      evidence that NGF receptors continue to signal after endocytosis. We have
      examined early events in the membrane traffic of NGF and its receptor,
      gp140(TrkA) (TrkA), in PC12 cells. NGF induced rapid and extensive endocytosis of
      TrkA in these cells, and the receptor subsequently moved into small organelles
      located near the plasma membrane. Some of these organelles contained clathrin and
      alpha-adaptin, which implies that TrkA is internalized by clathrin-mediated
      endocytosis. Using mechanical permeabilization and fractionation, intracellular
      organelles derived from endocytosis were separated from the plasma membrane.
      After NGF treatment, NGF was bound to TrkA in endocytic organelles, and TrkA was
      tyrosine-phosphorylated and bound to PLC-gamma1, suggesting that these receptors
      were competent to initiate signal transduction. These studies raise the
      possibility that NGF induces formation of signaling endosomes containing
      activated TrkA. They are an important first step in elucidating the molecular
      mechanism of NGF retrograde signaling.

PMID- 8987824
TI  - Changing patterns of expression and subcellular localization of TrkB in the
      developing visual system.
AB  - Neurotrophins play important roles in the survival, differentiation, and
      maintenance of CNS neurons. To begin to investigate specific roles for these
      factors in the mammalian visual system, we have examined the cellular
      localization of the neurotrophin receptor trkB within the developing cerebral
      cortex and thalamus of the ferret using extracellular domain-specific antibodies.
      At prenatal ages (gestation is 41 d), trkB-immunostained fibers were observed in
      the internal capsule and as two distinct fascicles within the intermediate zone
      of the cerebral cortex. The staining of these fiber tracts declined with
      increasing age, whereas soma and dendrite staining of cortical neurons was first
      evident in early postnatal life and increased during subsequent development.
      Staining of subplate neurons [by prenatal day 5 (P5)] was followed by staining of
      cortical layer 5 neurons (at P10). By P31, trkB immunoreactivity was particularly
      prominent in layers 3 and 5 but was absent from subplate neurons. Staining
      included cells, especially pyramidal neurons, in all cortical layers by P45, and
      this pattern was maintained into adulthood. The optic tract and fibers within the
      lateral geniculate nucleus (LGN) were also strongly trkB immunoreactive at
      prenatal ages. Cellular staining of a subset of LGN neurons, those within the C
      layers and perigeniculate nucleus, was apparent by P10 and maintained until P45,
      when the adult pattern of highly trkB-immunoreactive neurons in all layers of the
      LGN first appeared. The pattern of trkB immunoreactivity suggests that specific
      subsets of cortical and thalamic neurons may respond to neurotrophins such as
      brain-derived neurotrophic factor and/or NT-4/5 at discrete developmental times
      and locations. The appearance of trkB on axon fibers early in development and
      then on cell bodies and dendritic processes later is consistent with roles for
      both long-range and local, including autocrine and/or paracrine, delivery of
      neurotrophins in cell survival and maturation.

PMID- 8987825
TI  - Origin of oligodendrocytes within the human spinal cord.
AB  - To determine the time and site of origin of the oligodendrocyte lineage in the
      developing human spinal cord, we have examined tissues from 45 to 83 d
      postconception (dpc) using sets of probes and antibodies recognizing
      oligodendrocyte-specific glycolipids, transcripts, and proteins. We found that
      two clusters of oligodendrocyte precursors appear on or before 45 dpc on each
      side of the cord ventral ependyma above the floor plate. These precursors express
      glycolipids recognized by the O4 and Rmab antibodies, platelet-derived growth
      factor alpha-receptor, myelin basic protein (MBP), and 2', 3'-cyclic nucleotide
      3' phosphodiesterase as well as MBP and proteolipid transcripts. Expression of
      the morphogen sonic hedgehog was detected in the floor plate at 45 dpc and
      decreased at 58 dpc. During this period, oligodendrocyte precursors emerged in
      the ventral and lateral region of the forming white matter, a process occurring
      first in cervical and later in lumbar cord. The majority of O4(+) cells express
      the proliferating cell nuclear antigen (PCNA), and their pattern of dispersion
      suggests that these cells progressively populate the lateral and dorsal cord
      regions. Oligodendrocytes expressing galactocerebroside appeared at 53 dpc and
      did not express PCNA. Oligodendrocyte precursors were detected in dorsal cord
      regions at 74 dpc and at 83 dpc when myelination started in the ventral roots.
      Thus, oligodendrocyte precursors expressing myelin transcripts and proteins
      emerge in the ventral region of the embryonic cord several weeks before
      myelination.

PMID- 8987826
TI  - A role for nitric oxide in the development of the ferret retinogeniculate
      projection.
AB  - The ferret retinogeniculate projection segregates into eye-specific layers during
      the first postnatal week and into ON/OFF sublaminae, which receive inputs from
      either on-center or off-center retinal ganglion cells, during the third and
      fourth postnatal weeks. The restriction of retinogeniculate axon arbors into eye
      specific layers appears to depend on action potential activity () but does not
      require activation of NMDA receptors (). The formation of ON/OFF sublaminae is
      also activity-dependent and is disrupted by in vivo blockade of NMDA receptors
      (). To investigate a possible mechanism whereby blockade of postsynaptic NMDA
      receptors in the lateral geniculate nucleus (LGN) results in changes in the size
      and position of presynaptic axon arbors, we tested the role of the diffusible
      messenger nitric oxide (NO) in the development of the retinogeniculate pathway.
      We found previously that NO synthase (NOS) is transiently expressed in LGN cells
      during the refinement of retinogeniculate projections (). In this study,
      treatment with NG-nitro-L-arginine (L-NoArg), an arginine analog that inhibits
      NOS, during the third and fourth postnatal weeks resulted in an overall pattern
      of sublamination that was significantly reduced compared with normal and control
      animals. Single retinogeniculate axon arbors were located in the middle of eye
      specific layers rather than toward the inner or outer half as in normal or
      control animals. The effect of NOS inhibition was not a consequence of the
      hypertensive effect of L-NoArg. In contrast to the effect of L-NoArg on the
      formation of ON/OFF sublaminae, treatment with L-NoArg during the first postnatal
      week did not disrupt the formation of eye-specific layers. Biochemical assays
      indicated significant inhibition of NOS during both treatment periods. These data
      suggest that NO acts together with NMDA receptors in activity-dependent
      refinement of connections during a specific phase of retinogeniculate
      development.

PMID- 8987827
TI  - Chondroitin sulfate proteoglycan and tenascin in the wounded adult mouse
      neostriatum in vitro: dopamine neuron attachment and process outgrowth.
AB  - Extracellular matrix (ECM) molecules, including chondroitin-4 or chondroitin-6
      sulfate proteoglycans (CSPGs) and tenascin, are upregulated in and around wounds
      and transplants to the adult CNS. In the present study, striatal wounds from
      adult mice were used in a novel in vitro paradigm to assess the effects of these
      wound-associated molecules on embryonic dopamine cell attachment and neurite
      outgrowth. Light and electron microscopic immunocytochemistry studies have shown
      that astroglial scar constituents persist in cultured explants for at least 1
      week in vitro, and despite the loss of neurons from adult striatal explants,
      there is a retention of certain structural features suggesting that the wound
      explant-neuron coplant is a viable model for analysis of graft-scar interactions.
      Explants from the wounded striatum taken at different times after a penetrating
      injury in vivo were used as substrates for embryonic ventral mesencephalon
      neurons that were plated on their surfaces. Dopamine cell attachment is increased
      significantly in relation to the expression of both CSPG and tenascin. The
      increase in neuronal attachment in this paradigm, however, is accompanied by a
      postlesion survival time-dependent significant decrease in neuritic growth from
      these cells. In vitro ECM antibody treatment suggests that CSPG may be
      responsible for heightened dopamine cell attachment and that tenascin
      simultaneously may support cell attachment while inhibiting neurite growth. The
      present study offers a new approach for the in vitro analysis of cell and
      molecular interactions after brain injury and brain grafting, in essence acting
      as a nigrostriatal transplant-in-a-dish.

PMID- 8987828
TI  - Influence of cocaine on the JAK-STAT pathway in the mesolimbic dopamine system.
AB  - Chronic exposure to cocaine produces characteristic biochemical adaptations
      within the rat ventral tegmental area (VTA), a brain region rich in dopaminergic
      neurons implicated in the reinforcing and locomotor-activating properties of
      cocaine. Some of these changes are mimicked by chronic ciliary neurotrophic
      factor (CNTF) infusions into the same brain area. We show in this study that
      chronic cocaine treatment regulates the signal transduction pathway used by CNTF
      specifically in the VTA. There is an increase in immunoreactivity of Janus kinase
      (JAK2), a CNTF-regulated protein tyrosine kinase, in the VTA after chronic but
      not acute cocaine administration. This increase is not seen in the nearby
      substantia nigra or several other brain regions studied. Furthermore, this
      increase in JAK2 is not seen after chronic administration of other psychotropic
      drugs and was not observed for JAK1. The increase in JAK2 levels is associated
      with an increased responsiveness of the system to acute CNTF infusion into the
      VTA, as measured by induction in this brain region of signal transducers and
      activators of transcription (STAT) DNA binding activity and of Fos-like proteins,
      two known functional endpoints of JAK activation. Double-labeling
      immunohistochemical studies show that JAK2 immunoreactivity in the VTA is
      enriched in dopaminergic and nondopaminergic cells, both of which exhibit
      increased JAK2 immunoreactivity after chronic cocaine treatment. These findings
      suggest a scheme whereby some of the effects of chronic cocaine on VTA
      dopaminergic neurons are mediated directly by regulation of the JAK-STAT pathway
      in these cells, as well as perhaps indirectly by regulation of this pathway in
      nondopaminergic cells.

PMID- 8987829
TI  - Dynamics of mismatch correction in the hippocampal ensemble code for space:
      interaction between path integration and environmental cues.
AB  - Populations of hippocampal neurons were recorded simultaneously in rats shuttling
      on a track between a fixed reward site at one end and a movable reward site,
      mounted in a sliding box, at the opposite end. While the rat ran toward the fixed
      site, the box was moved. The rat returned to the box in its new position. On the
      initial part of all journeys, cells fired at fixed distances from the origin,
      whereas on the final part, cells fired at fixed distances from the destination.
      Thus, on outward journeys from the box, with the box behind the rat, the position
      representation must have been updated by path integration. Farther along the
      journey, the place field map became aligned on the basis of external stimuli. The
      spatial representation was quantified in terms of population vectors. During
      shortened journeys, the vector shifted from an alignment with the origin to an
      alignment with the destination. The dynamics depended on the degree of mismatch
      with respect to the full-length journey. For small mismatches, the vector moved
      smoothly through intervening coordinates until the mismatch was corrected. For
      large mismatches, it jumped abruptly to the new coordinate. Thus, when mismatches
      occur, path integration and external cues interact competitively to control place
      cell firing. When the same box was used in a different environment, it controlled
      the alignment of a different set of place cells. These data suggest that although
      map alignment can be controlled by landmarks, hippocampal neurons do not
      explicitly represent objects or events.

PMID- 8987830
TI  - Synaptic inputs to ON parasol ganglion cells in the primate retina.
AB  - In primates, the retinal ganglion cells that project to the magnocellular layers
      of the lateral geniculate nucleus have distinctive responses to light, and one of
      these has been identified morphologically as the parasol ganglion cell. To
      investigate their synaptic connections, we injected parasol cells with
      Neurobiotin in lightly fixed baboon retinas. The five ON-center cells we analyzed
      by electron microscopy received approximately 20% of their input from bipolar
      cells. The major synaptic input to parasol cells was from amacrine cells via
      conventional synapses and, in this respect, they resembled alpha ganglion cells
      of the cat retina. We also found the gap junctions between amacrine cells and
      parasol ganglion cells that had been predicted from tracer-coupling experiments.
      To identify the presynaptic amacrine cells, ON-center parasol cells were injected
      with Neurobiotin and Lucifer yellow in living macaque retinas, which were then
      fixed and labeled by immunofluorescence. Two kinds of amacrine cells were filled
      with Neurobiotin via gap junctions: a large, polyaxonal cell containing
      cholecystokinin and a smaller one without cholecystokinin. There were also
      appositions between cholecystokinin-containing amacrine cell processes and
      parasol cell dendrites. Cholinergic amacrine cell processes often followed
      parasol cell dendrites and made extensive contacts. In other mammals, the light
      responses of polyaxonal amacrine cells like these and cholinergic amacrine cells
      have been recorded, and the effects of acetylcholine and cholecystokinin on
      ganglion cells are known. Using this information, we developed a model of parasol
      cells that accounts for some properties of their light responses.

PMID- 8987832
TI  - Local control of leg movements and motor patterns during grooming in locusts.
AB  - This study demonstrates that the thoracic and abdominal nervous system of locusts
      is sufficient to mediate several site-specific and distinct grooming leg
      movements. Locusts can use a hindleg or middle leg to groom at least four
      ipsilateral thoracic and abdominal sites, without input from the brain,
      subesophageal ganglion, or prothoracic ganglion. The hindleg is used to groom the
      posterior abdomen, the ventral or posterior hindleg coxa, and the ear; the middle
      leg is used to groom the anterior hindleg coxa. Grooming movements are often
      rhythmic and display site-specific intralimb coordination patterns. During
      grooming of the posterior abdomen or ventral hindleg coxa, for example, hindleg
      tibial extension occurs nearly simultaneously with femur elevation, in contrast
      with locust hindleg movements during walking. Electromyographic (EMG) recordings
      during these movements show that rhythmic bursts of tibial extensor activity
      occur nearly in-phase with those of trochanteral levators, in contrast to hindleg
      EMGs during walking. During grooming of the ear, hindleg tibial extension/flexion
      and tibial extensor/flexor muscle bursts can occur independently of the femur
      elevation/depression and trochanteral levator/depressor muscle bursts, suggesting
      that the neural modules controlling tibial and femoral movements can be uncoupled
      during this behavior. Tibial extension can occur before, or even in the absence
      of, tibial extensor muscle activity, suggesting that spring-like properties of
      the leg and energy transfer from femur motion may play important roles in such
      leg movements. Adjacent legs sometime show coordinated femur movement during
      grooming with one hindleg, suggesting that grooming may also involve interlimb
      coordination.

PMID- 8987831
TI  - Effects of chronic treatment with delta9-tetrahydrocannabinol on cannabinoid
      stimulated [35S]GTPgammaS autoradiography in rat brain.
AB  - Chronic Delta9-tetrahydrocannabinol (Delta9-THC) administration produces
      tolerance to cannabinoid effects, but alterations in signal transduction that
      mediate these changes are not yet known. The present study uses in vitro
      autoradiography of agonist-stimulated [35S]GTPgammaS binding to localize
      cannabinoid receptor-activated G-proteins after chronic Delta9-THC treatment.
      Cannabinoid (WIN 55212-2)-stimulated [35S]GTPgammaS binding was performed in
      brain sections from rats treated chronically with 10 mg/kg Delta9-THC for 21 d.
      Control animals received saline or an acute injection of Delta9-THC. Acute Delta9
      THC treatment had no effect on basal or WIN 55212-2-stimulated [35S]GTPgammaS
      binding. After chronic Delta9-THC treatment, net WIN 55212-2-stimulated
      [35S]GTPgammaS binding was reduced significantly (up to 70%) in most brain
      regions, including the hippocampus, caudate-putamen, perirhinal and entorhinal
      cortex, globus pallidus, substantia nigra, and cerebellum. In contrast, chronic
      Delta9-THC treatment had no effect on GABAB-stimulated [35S]GTPgammaS binding. In
      membranes and brain sections, Delta9-THC was a partial agonist, stimulating
      [35S]GTPgammaS by only 20% of the level stimulated by WIN 55212-2 and inhibiting
      WIN 55212-2-stimulated [35S]GTPgammaS at high concentrations. Because the EC50 of
      WIN 55212-2-stimulated [35S]GTPgammaS binding and the KD of cannabinoid receptor
      binding were unchanged by chronic Delta9-THC treatment, the partial agonist
      actions of Delta9-THC did not produce the decrease in cannabinoid-stimulated
      [35S]GTPgammaS binding. These results suggest that profound desensitization of
      cannabinoid-activated signal transduction mechanisms occurs after chronic Delta9
      THC treatment.

PMID- 8987833
TI  - Central generation of grooming motor patterns and interlimb coordination in
      locusts.
AB  - Coordinated bursts of leg motoneuron activity were evoked in locusts with
      deefferented legs by tactile stimulation of sites that evoke grooming behavior.
      This suggests that insect thoracic ganglia contain central pattern generators for
      directed leg movements. Motoneuron recordings were made from metathoracic and
      mesothoracic nerves, after eliminating all leg motor innervation, as well as all
      input from the brain, subesophageal ganglion, and prothoracic ganglion. Strong,
      brief trochanteral levator motoneuron bursts occurred, together with silence of
      the slow and fast trochanteral depressor motoneurons and activation of the common
      inhibitor motoneuron. The metathoracic slow tibial extensor motoneuron was active
      in a pattern distinct from its activity during walking or during rhythms evoked
      by the muscarinic agonist pilocarpine. Preparations in which the metathoracic
      ganglion was isolated from all other ganglia could still produce fictive motor
      patterns in response to tactile stimulation of metathoracic locations. Bursts of
      trochanteral levator and depressor motoneurons were clearly coordinated between
      the left and right metathoracic hemiganglia and also between the mesothoracic and
      the ipsilateral metathoracic ganglia. These data provide clear evidence for
      centrally generated interlimb coordination in an insect.

PMID- 8987834
TI  - Costorage and corelease of modulatory peptide cotransmitters with partially
      antagonistic actions on the accessory radula closer muscle of Aplysia
      californica.
AB  - Many neurons that contain a classical neurotransmitter also contain modulatory
      peptides, but it has been difficult to establish unequivocally that these
      peptides are functional cotransmitters. Here, we provide evidence for functional
      cotransmission in a neuromuscular system of Aplysia. Using immunocytochemical
      techniques, we localize members of two peptide families, the small cardioactive
      peptides (SCPs) and the buccalins (BUCs), to a single subset of dense-core
      vesicles in the terminals of the cholinergic motorneuron B15. We describe a new
      preparation and method for the direct detection of released peptides and show
      that the SCPs and BUCs are released when neuron B15 is intracellularly
      stimulated. Consistent with their subcellular localization, the SCPs and BUCs are
      released in a stoichiometric ratio that is constant across conditions that change
      the absolute amount of peptides released. Peptide release is calcium-dependent
      but does not require muscle contractions. Thus, the release cannot be attributed
      to a displacement of peptides that may be present in the extracellular space. In
      previous studies, we characterized the physiological firing patterns of neuron
      B15. Here, we simulate these firing patterns and show that peptide release
      occurs. Additionally, we find that significant quantities of material are
      released under behaviorally relevant conditions. We find that concentrations of
      released peptides in the muscle are in the concentration range in which
      exogenously applied peptides exert characterized modulatory actions on muscle
      contractions. Together, our findings provide strong support for the hypothesis
      that peptides contained in neuron B15 are functional cotransmitters.

PMID- 8987835
TI  - Release of peptide cotransmitters in Aplysia: regulation and functional
      implications.
AB  - To gain insights into the physiological role of cotransmission, we measured
      peptide release from cell B15, a motorneuron that utilizes ACh as its primary
      transmitter but also contains putative peptide cotransmitters, the small
      cardioactive peptides (SCPs) and the buccalins (BUCs). All stimulation parameters
      used were in the range in which B15 fires in freely moving animals. We stimulated
      neuron B15 in bursts and systematically varied the interburst interval, the
      intraburst frequency, and burst duration. Both peptides were preferentially
      released when B15 was stimulated at higher intra- or interburst frequencies or
      with longer burst durations. Across stimulation patterns, the amount of peptide
      released depended on the mean frequency of stimulation and was independent of the
      specific pattern of stimulation. The parameters of stimulation that produce a
      larger release of peptides correspond to those that evoke larger contractions.
      Large and frequent contractions are likely to fuse or summate, thus disrupting
      the rhythmic behavior mediated by the muscle innervated by motorneuron B15.
      Because the combined effect of the SCPs and BUCs is to accelerate the relaxation
      and shorten the duration of muscle contractions, these peptides reduce the
      probability of the disruptive fusion or summation of muscle contractions. Because
      these cotransmitters regulate an aspect of muscle contractions that is not
      controlled by acetylcholine (ACh), the primary transmitter of B15, we suggest
      that peptides and ACh form parallel but functionally distinct lines of
      transmission at the neuromuscular junction. Both types of transmission may be
      necessary to ensure that behavior remains efficient over a wide range of
      conditions.

PMID- 8987836
TI  - Amiloride disrupts NaCl versus KCl discrimination performance: implications for
      salt taste coding in rats.
AB  - Amiloride, an epithelial sodium channel blocker, suppresses the responsiveness of
      narrowly tuned sodium-responsive taste afferents when orally applied in the rat.
      Broadly tuned salt-responsive taste afferents, which respond to sodium and
      nonsodium salts and acids, are relatively unaffected by the drug. We used
      amiloride treatment to examine the consequences of the specific removal of input
      from narrowly tuned sodium-responsive afferents on taste discrimination. Five
      water-restricted rats were trained in a gustometer to press one lever after
      licking NaCl and another lever after licking KCl across a range of concentrations
      (0.05, 0.1, and 0.2 M). Correct responses were rewarded with brief water access,
      and incorrect responses were punished with a time-out. After training, animals
      averaged about 90% correct responses and maintained competent performance during
      subsequent control sessions. Amiloride was then placed in all solutions at a
      given concentration (1-100 microM) for single test sessions. Control sessions
      were interposed between amiloride sessions. At high amiloride concentrations,
      overall responding was reduced to 50% correct and progressively improved as the
      drug concentration was lowered. The sigmoidal dose-response functions
      corresponded quantitatively with electrophysiological findings. Performance
      deficits occurred primarily with NaCl and were concentration dependent;
      performance during KCl trials was relatively undisturbed by amiloride
      adulteration. At high amiloride concentrations, rats treated NaCl as if it were
      KCl. Given that amiloride is tasteless to the rat, these results provide
      convincing evidence of the importance of narrowly tuned afferents in the
      discrimination between sodium and nonsodium salts and suggest that this is a
      general coding principle in the gustatory system.

PMID- 8987837
TI  - Endogenous activation of mu and delta-1 opioid receptors is required for long
      term potentiation induction in the lateral perforant path: dependence on
      GABAergic inhibition.
AB  - Opioid peptides costored with glutamate have emerged as powerful regulators of
      long-term potentiation (LTP) induction in several hippocampal pathways. The
      objectives of the present study were twofold: (1) to identify which opioid
      receptor types (mu, delta, or kappa) regulate LTP induction at lateral perforant
      path-granule cell synapses and (2) to test the hypothesis that endogenous opioids
      regulate LTP induction via modulation of GABAergic inhibition. LTP of lateral
      perforant path-evoked field EPSPs was induced selectively by high-frequency
      stimulation applied to the outer third of the molecular layer of the dentate
      gyrus of rat hippocampal slices. No changes in medial perforant path responses
      occurred. LTP was blocked when high-frequency stimulation was applied in the
      presence of the mu receptor antagonist CTAP, the selective delta-1 receptor
      antagonist BNTX, or the delta-1 and delta-2 receptor antagonist naltrindole. By
      contrast, the kappa-1 opioid receptor antagonist NBNI had no effect on LTP
      induction. The role of GABAergic inhibition was investigated by comparing the
      effect of naloxone on LTP induction in slices maintained in standard buffer and
      picrotoxin-containing buffer. Naloxone blocked LTP in standard buffer, whereas
      normal LTP was induced in picrotoxin-treated, disinhibited slices. Finally, NMDA
      receptor blockade completely inhibited LTP in both standard and disinhibited
      slices. The results show that mu and delta-1 opioid receptors regulate LTP
      induction and that this mechanism critically depends on GABAergic inhibition. A
      key issue then becomes how endogenous opioids fine-tune the activity of intact
      inhibitory networks in the dentate gyrus, effectively gating synaptic plasticity
      in specific dendritic strata.

PMID- 8987838
TI  - GDNF selectively protects dopamine neurons over serotonin neurons against the
      neurotoxic effects of methamphetamine.
AB  - Repeated methamphetamine (METH) administration to animals can result in long
      lasting decreases in striatal dopamine (DA) and serotonin (5-HT) levels. Glial
      cell line-derived neurotrophic factor (GDNF) has pronounced effects on
      dopaminergic systems in vivo, including partial neuroprotective effects against 6
      hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -induced
      lesions. The present study examined the ability of GDNF to prevent METH-induced
      reductions in potassium-evoked overflow of DA, and DA and 5-HT content, in
      striatum. GDNF (10 microg) or vehicle was injected into the right striatum of
      anesthetized rats. Twenty-four hours later, the rats were injected four times at
      2 hr intervals with METH (5 mg/kg, s.c.) or saline. One week later, in vivo
      electrochemistry was used to monitor the overflow of DA evoked by local potassium
      application. Evoked overflow of DA was dramatically decreased in the striatum of
      METH-treated animals. GDNF prevented the reduction in evoked overflow of DA in
      the right striatum of the METH-treated animals. After each experiment, the
      animals were killed, and striatal DA and 5-HT levels determined by HPLC. The METH
      treatment produced significant decreases in both neurotransmitters. GDNF
      administration prevented the reduction in striatal DA levels on the treated side
      of the brain, whereas levels on the contralateral side were still decreased. In
      dose-response studies, 1 microg of GDNF was as protective as 10 microg, whereas
      0.1 microg was only partially protective. In contrast, 5-HT levels were only
      minimally protected by previous administration of GDNF. These results suggest
      that GDNF can selectively protect DA neurons, compared with 5-HT neurons, against
      the neurotoxic effects of METH.

PMID- 8987839
TI  - Central administration of a growth hormone (GH) receptor mRNA antisense increases
      GH pulsatility and decreases hypothalamic somatostatin expression in rats.
AB  - To test the hypothesis of the involvement of centrally expressed rat growth
      hormone receptors (rGH-R) in the ultradian rhythmicity of pituitary GH secretion,
      adult male rats were submitted to a 60 hr intracerebroventricular infusion of an
      antisense (AS) oligodeoxynucleotide (ODN) complementary to the sequence of rGH-R
      mRNA. Eight hour (10 A.M.-6 P.M.) GH secretory profiles, obtained from freely
      moving male rats infused with 2.0 nmol/hr of rGH-R AS, revealed a marked increase
      in GH peak amplitude (150 +/- 12 vs 101 +/- 10 ng/ml), trough levels (16.2 +/-
      3.0 vs 5.4 +/- 1.4 ng/ml), and number of peaks (2.9 +/- 0.3 vs 1.8 +/- 0.2). No
      change was observed in rats treated with an ODN complementary to the prolactin
      receptor mRNA sequence (2.0 nmol/hr). Infusion of increasing ODN concentrations
      resulted in a dose-dependent stimulation of GH release. In parallel, somatogenic
      binding sites in the choroid plexus were decreased by 40%, and levels of rGH-R
      mRNA were increased in the periventricular nucleus (PeV) but unchanged in the
      arcuate nucleus (ARC). Levels of somatostatin mRNA, in the PeV but not in the
      ARC, were lowered by the treatment. Levels of GH-releasing hormone mRNA in the
      ARC were not affected. These data suggest that GH negative feedback results from
      a direct effect on central GH receptors and a subsequent activation of
      hypophysiotropic somatostatin neurons located in the anterior periventricular
      hypothalamus.

PMID- 8987840
TI  - Spontaneous discharge and peripherally evoked orofacial responses of trigemino
      thalamic tract neurons during wakefulness and sleep.
AB  - In the present study, ongoing and evoked activity of antidromically identified
      trigemino-thalamic tract (TGT) neurons was examined over the sleep-wake cycle in
      cats. There was no difference in the mean spike discharge rate of TGT neurons
      when quiet sleep (QS) and active sleep (AS) were compared with wakefulness (W).
      However, tooth pulp-evoked responses of TGT neurons were decreased during AS when
      compared to W. Conversely, the responses of TGT neurons to air puff activation of
      facial hair mechanoreceptors reciprocally increased during AS when compared to W.
      The present data demonstrate that ascending sensory information emanating from
      distinct orofacial areas is differentially modified during the behavioral state
      of AS. Specifically, the results obtained suggest that during AS, sensory
      information arising from hair mechanoreceptors is enhanced, whereas information
      arising from tooth pulp afferents is suppressed. These data may provide
      functional evidence for an AS-related gate control mechanism of sensory outflow
      to higher brain centers.

PMID- 8987841
TI  - Behavior-relevant changes in nucleus accumbens dopamine transmission elicited by
      food reinforcement: an electrochemical study in rat.
AB  - Voltammetry was used to monitor dopamine (DA) transmission in nucleus accumbens
      (NAcc) of rats lever-pressing for food. Under standard conditions, animals
      responded on a fixed ratio 1 (FR1) schedule for 0.2 ml of milk delivered over 30
      sec; milk delivery was paired with a 30 sec cue light. Consumption of the initial
      few milk rewards of the session caused DA signal increases. These initial signal
      increases were typical of the first and, at times, the second test days. On
      subsequent days, the most pronounced initial signal increases coincided with
      presentation of conditioned stimuli that marked the start of the session.
      Biphasic changes in DA signal that were time-locked to each reinforced lever
      press were also observed; responses were preceded by increases and were followed,
      during milk consumption, by decreases in DA signal. At the end of milk delivery,
      the signal increased again in apparent anticipation of the next lever-press.
      Delaying milk delivery caused a corresponding delay in DA signal decreases, and
      the amount of time signals remained depressed was bound by the duration of milk
      consumption. Greater decreases in DA signal were observed when the rate of milk
      delivery was doubled or tripled, and such increases in reward value were
      associated with more pronounced signal increases during the period that preceded
      each lever-press. In contrast, DA signal increases were seen when milk was
      delivered at half the usual rate or was withheld altogether or when animals were
      denied access to the lever. Under partial reinforcement conditions, reinforced
      lever-presses were preceded by more pronounced signal increases and decreases of
      comparable magnitude accompanied milk consumption. These results suggest that
      meso-NAcc DA neurons are activated primarily in response to the incentive rather
      than to the reinforcing properties of rewards.

PMID- 8987842
TI  - The hypothalamic ventromedial nuclei couple activity in the hypothalamo-pituitary
      adrenal axis to the morning fed or fasted state.
AB  - Function in the adrenocortical system is markedly altered by availability of
      food. Basal activity is lowest and stress responsivity highest in the morning
      when nocturnal rats eat approximately 90% of their daily calories during the
      dark. After an overnight fast, basal corticotrophin and corticosteroid levels are
      elevated, and responsivity to stressors is decreased. Central neural sites that
      control these changes are unidentified. The hypothalamic ventromedial nuclei
      (VMN) appear to signal satiety; lesions result in increased food intake, obesity,
      and elevated basal insulin and corticosteroids. Thus, the VMN are good candidates
      for calorically mediated control of adrenocortical system function in satiated
      rats. We injected colchicine into the VMN to cause reversible inhibition of
      activity (Avrith and Mogenson, 1978) and tested the effects on basal and
      stimulated function in the adrenocortical system. Colchicine-injected rats that
      fed ad libitum exhibited increased basal but reduced corticotrophin and
      corticosterone responses to restraint in the morning compared with controls. By
      contrast, after an overnight fast, control rats had increased basal
      adrenocortical hormones and decreased stress responses that did not differ from
      colchicine-injected rats. Colchicine was visualized within cells in the VMN for
      up to 5 d using fluorescein/colchicine, and the treatment did not cause increased
      gliosis; moreover, the functional effects of the injections were reversed within
      15 d. We conclude that (1) the VMN serve to couple activity in the adrenocortical
      system to energy intake and (2) discrete colchicine injections provide a
      behaviorally and neuroendocrinologically useful period of inhibition without
      causing permanent functional damage.

PMID- 8987843
TI  - Ultrastructural localization suggests that retinal and cortical inputs access
      different metabotropic glutamate receptors in the lateral geniculate nucleus.
AB  - Glutamate has an important neuromodulatory role in synaptic transmission through
      metabotropic glutamate receptors (mGluRs) linked to a variety of G-protein
      coupled second messenger pathways. Activation of these receptors on relay cells
      in the lateral geniculate nucleus (LGN) with the agonist trans-(1S,3R)-1-amino-1,
      3-cyclopentanedicarboxylic acid produces a membrane depolarization that
      inactivates the low-threshold Ca2+ spike, causing a transition from burst to
      tonic response mode. The excitatory effects of metabotropic receptor activation
      in the LGN appear to be produced through the receptors linked to phosphoinositide
      hydrolysis and apparently only through activation of the corticogeniculate
      pathway. Two mGluRs, mGluR1alpha (a splice variant of mGluR1) and mGluR5, are
      linked to the phosphoinositide system. We examined the localization of these
      receptors with affinity-purified, anti-peptide, polyclonal antibodies raised to
      the C-terminal region of each receptor protein. Under examination with the light
      microscope, we found that both types of receptors are present in the geniculate
      neuropil and in that of the overlying thalamic reticular nucleus, including the
      perigeniculate nucleus. We also examined the ultrastructural localization of
      immunolabel with the electron microscope, using a postembedding immunogold marker
      to identify terminals, dendrites, and somata that contain GABA. Label for the
      antibody directed against mGluR1alpha was primarily localized in the dendrites of
      relay cells, postsynaptic to various terminal types. Of these, terminal profiles
      normally associated with corticogeniculate inputs predominated, whereas retinal
      terminal profiles were scarce. Label for the antibody directed against mGluR5
      label was prominent in inhibitory F2-terminal profiles associated with the
      retinal input to relay cells. In the perigeniculate nucleus, both mGluRs were
      localized to dendrites. The distribution of the two phosphoinositide-linked
      mGluRs in the LGN suggests very different functional roles for the two receptor
      types. We conclude from these data that mGluR1 appears to have a dominant role in
      corticogeniculate control of response mode through the feedback glutamatergic
      pathway from layer VI, whereas mGluR5 is positioned to affect retinogeniculate
      activation of relay cells through feed forward glomerular interactions.

PMID- 8987844
TI  - The influence of auditory and visual distractors on human orienting gaze shifts.
AB  - We studied the influences of competing visual and auditory stimuli on horizontal
      gaze shifts in humans. Gaze shifts were made to visual or auditory targets in the
      presence of either an irrelevant visual or auditory cue. Within an experiment,
      the target and irrelevant cue were either aligned (enhancer condition) or
      misaligned (distractor condition) in space. The times of presentation of the
      target and irrelevant cue were varied so that the target could have been
      presented before the irrelevant cue, or the irrelevant cue before the target. We
      compared subject performance in the enhancer and distractor conditions, measuring
      reaction latencies and the frequency of incorrect gaze shifts. Performance
      differed the most when the irrelevant cue was presented before the target and
      differed the least when the target was presented before the irrelevant cue. Our
      results reveal that, in addition to the spatial and temporal register of the
      stimuli, the experimental context in which the stimuli are presented also
      influences multisensory integration: an irrelevant auditory cue influenced gaze
      shifts to visual targets differently than an irrelevant visual cue influenced
      gaze shifts to auditory targets. Furthermore, we observed patterns of influence
      unique to either visual or auditory irrelevant cues that occurred regardless of
      the modality of the target. We believe that subjects adopted a state of motor
      readiness that reflected the unique demands of target selection in each
      experiment and that this state modulated the influences of the irrelevant cue on
      the target.

PMID- 8987846
TI  - Glucose uptake kinetics of Saccharomyces cerevisiae monitored with a newly
      developed FIA.
AB  - The glucose content of the culture liquid during shift experiments and
      synchronized cultures of Saccharomyces cerevisiae H1022 (ATCC 32167) was
      monitored using a greatly improved and highly precise FIA. During shift-up
      experiments on the dilution rate, an overshoot of the glucose-concentration was
      observed. The amplitude of the overshoot showed a dependency on the duration of
      undisturbed cultivation before application of the shift. Mutarotational non
      equilibrium was excluded as the cause of the observed overshoot. For the first
      time glucose measurements of oscillating cultures of Saccharomyces cerevisiae are
      demonstrated with high accuracy and reproducibility. The data strongly support
      the proposals by Munch et al. (1992a, b) that faint oscillations in glucose
      concentration are responsible for the persistence of the synchronization.
      Analytical subsystems prove to be a powerful tool for investigation of the
      dynamics of metabolic pathways of microbial organisms. Accurate glucose
      measurements at low concentrations point out the limits and allow refinements of
      commonly used models.

PMID- 8987845
TI  - 5HT1B receptor agonists inhibit light-induced phase shifts of behavioral
      circadian rhythms and expression of the immediate-early gene c-fos in the
      suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) is a circadian oscillator and a critical
      component of the mammalian circadian system. It receives afferents from the
      retina and the mesencephalic raphe. Retinal afferents mediate photic entrainment
      of the SCN, whereas the serotonergic afferents originating from the midbrain
      modulate photic responses in the SCN; however, the serotonin (5HT) receptor
      subtypes in the SCN responsible for these modulatory effects are not well
      characterized. In this study, we tested the hypothesis that 5HT1B receptors are
      located presynaptically on retinal axon terminals in the SCN and that activation
      of these receptors inhibits retinal input. The 5HT1B receptor agonists TFMPP and
      CGS 12066A, administered systemically, inhibited light-induced phase shifts of
      the circadian activity rhythm in a dose-dependent manner at phase delay and phase
      advance time points. This inhibition was not affected by previous systemic
      application of either the selective 5HT1A receptor antagonist (+)WAY 100135 or by
      the 5HT2 receptor antagonist mesulergine, whereas pretreatment with the
      nonselective 5HT1 antagonist methiothepin significantly attenuated the effect of
      TFMPP. TFMPP also produced a dose-dependent reduction in light-stimulated Fos
      expression in the SCN, although a small subset of cells in the dorsolateral
      aspect of the caudal SCN were TFMPP-insensitive. TFMPP (1 mM) infused into the
      SCN produced complete inhibition of light-induced phase advances. Finally,
      bilateral orbital enucleation reduced the density of SCN 5HT1B receptors as
      determined using [125I]-iodocyanopindolol to define 5HT1B binding sites. These
      results are consistent with the interpretation that 5HT1B receptors are localized
      presynaptically on retinal terminals in the SCN and that activation of these
      receptors by 5HT1B agonists inhibits retinohypothalamic input.

PMID- 8987847
TI  - Refolding, isolation and characterization of crystallizable human interferon
      alpha 8 expression in Saccharomyces cerevisiae.
AB  - Human interferon-alpha 8 was expressed in Saccharomyces cerevisiae and found to
      accumulate intracellularly in an insoluble form. The protein could be solubilized
      and converted to a biologically active form with high yield by a denaturation
      refolding procedure. The interferon-alpha 8 was further purified to apparent
      homogeneity by copper-chelate affinity chromatography and anion-exchange
      chromatography and fully characterized by sodium dodecylsulfate polyacrylamide
      gel electrophoresis (SDS-PAGE), N-terminal sequence analysis, mass spectrometry,
      circular-dichroism (CD) spectroscopy and specific activity. Secondary-structure
      predictions from CD spectroscopy indicate that the molecule is correctly folded.
      Peptide mapping supported the correct sequence and the expected disulfide-bridge
      connectivity. The purified protein elutes on reversed-phase high-pressure liquid
      chromatography (RP-HPLC) as two peaks. Electrospray mass spectrometry and N
      terminal sequence analysis of the minor component indicated the existence of an N
      terminal acetyl group for the later eluting HPLC-component. In anti-viral assays,
      the two IFN forms were equally active. Hexagonal crystals of this interferon
      preparation could be obtained. On the basis of the electrophoretic mobility, HPLC
      profile, and biological activity assay, the crystalline material was judged to be
      identical to the uncrystallized interferon. Interferon in crystallized form was
      found to be stable for up to 24 months and, therefore, could be used for long
      term storage, particularly for material intended for clinical use.

PMID- 8987849
TI  - Food allergy, oral tolerance and immunomodulation--their molecular and cellular
      mechanisms.
AB  - This paper describes the molecular and cellular mechanisms of food allergy and
      oral tolerance including immunomodulation. Food allergy is triggered by an
      aberrant immune response elicited by oral administration of dietary antigens.
      Oral tolerance is a state of immunological unresponsiveness induced by oral
      administration of dietary antigens and is thought to serve to suppress food
      allergy. This review first describes the characteristic properties of T and B
      cells relating to milk allergy and also the location of binding sites to T and B
      cells on allergen molecules. The immunogenicity of allergens is shown to be
      reduced by the modulations of the T cell binding site, using sophisticated
      methods such as site-specific mutagenesis. Furthermore, this review focuses on
      oral tolerance with special reference to the identification of lymphocyte
      compartment subsets and the immunological mechanism relating to oral tolerance.
      Finally, the application of oral tolerance for the treatment of allergy is
      speculated on.

PMID- 8987848
TI  - Inactivation of MET2 in brewer's yeast increases the level of sulfite in beer.
AB  - Brewer's yeasts sometimes produce inadequate or excessive amounts of sulfite, an
      antioxidant and flavour stabilizer, so means of controlling the sulfite
      production are desired. Understanding the physiology and regulation of the sulfur
      assimilation pathway of Saccharomyces yeasts is the key to change sulfite
      production. The MET2 gene of Saccharomyces yeasts encodes homoserine O-acetyl
      transferase, which catalyzes the conversion of homoserine to O-acetyl homoserine
      which in turn combines with hydrogen sulfide to form homocysteine, the immediate
      precursor of methionine. We expected that inactivation of MET2 would lead to
      accumulation of sulfide and derepression of the entire sulfur assimilation
      pathway and, therefore, possibly also to sulfite accumulation. Brewer's yeasts
      were constructed in which several of the four MET2 gene copies were inactivated.
      Sulfite production was increased in strains with one remaining MET2 gene and even
      more so when no active MET2 was present. In both cases, hydrogen sulfide
      production was also increased. To the extent that excess sulfide can be removed,
      this strategy may be applied to control sulfite accumulation by brewer's yeast in
      beer production.

PMID- 8987850
TI  - Fractal analysis of aggregates formed by heating dilute BSA solutions using light
      scattering methods.
AB  - The structure of aggregates formed by heating dilute BSA solution was analyzed
      with fractal concept using light scattering methods. BSA was dissolved in HEPES
      buffer on pH 7.0 and acetate buffer of pH 5.1 to 0.1% and 0.001% solutions,
      respectively, and heated at 95 degrees C, varying the heating time ta. The
      fractal dimension Df of the aggregate in the solution was evaluated from static
      light scattering experiments. The polydispersity exponent tau and the average
      hydrodynamic radius <Rh> of the aggregates were calculated from dynamic light
      scattering experiments using master curves obtained by Klein et al. The values of
      Df and tau of heat-induced aggregates of BSA at pH 7.0 were about 2.1 and 1.5,
      respectively, the values of which agreed with those predicted by the reaction
      limited cluster-cluster aggregation (RLCCA) model. On the other hand, Df of heat
      induced aggregates at pH 5.1 was about 1.8, which agreed with that predicted by
      the diffusion-limited cluster-cluster aggregation (DLCCA) model. The dependence
      of <Rh> for the sample of pH 7.0 on ta was similar to that of the polystyrene
      colloids reported previously.

PMID- 8987851
TI  - Transmural potential changes associated with the in vitro absorption of theanine
      in the guinea pig intestine.
AB  - Theanine, L-N-ethylglutamine, is one of the major components of amino acids in
      Japanese green tea. To characterize the mode for intestinal absorption of
      theanine, the ionic dependency and kinetic properties of the theanine- and
      glutamine-evoked transmural electrical potential difference changes (delta PD)
      were investigated in vitro by using everted sacs prepared from the guinea pig
      ileum. Both theanine and glutamine applied to the luminal side induced dose
      dependent increases in delta PD (increase in serosal positive value). The
      theanine- and glutamine-evoked delta PD values conformed to the Michaelis-Menten
      relationship, with delta PDmax not being different, whereas the half-saturation
      concentration was lower for glutamine (3.1 +/- 0.2 mM) than for theanine (21.4 +/
      0.6 mM). The theanine-evoked delta PD value was much smaller when theanine was
      applied in the presence of glutamine than when applied alone. The theanine- and
      glutamine-evoked delta PD values were both inhibited by removing Na+ from the
      luminal solution. These results suggest that the intestinal absorption of
      theanine and glutamine is mediated by a common Na(+)-coupled co-transporter in
      the brush-border membrane, the affinity of which is lower for theanine than for
      glutamine.

PMID- 8987852
TI  - Sequence-specific binding sites in the Taka-amylase A G2 promoter for the CreA
      repressor mediating carbon catabolite repression.
AB  - The N-terminal part of the CreA protein encompassing two zinc fingers was
      expressed in Escherichia coli as a fusion protein with the maltose binding
      protein (MalE) of E. coli. Our results show that CreA binds to the promoter of
      the Taa-G2 gene encoding Taka-amylase A of Aspergillus oryzae. DNase I
      footprinting experiments showed that CreA bound to three sites with high affinity
      and to one site with low affinity within the first 401-bp region upstream of the
      transcription initiation site. All of the sites contained sequences related to
      the CreA consensus binding site (5'-SYGGRG-3'), and are suggested to participate
      in repression of the Taa-G2 gene in response to glucose.

PMID- 8987853
TI  - Molecular cloning and nucleotide sequences of cDNA and gene encoding endo
      inulinase from Penicillium purpurogenum.
AB  - A cDNA and a gene encoding endo-inulinase from Penicillium purpurogenum were
      isolated, and were cloned for the first time. Two oligonucleotide probes, which
      were synthesized based on the partial amino acid sequences of the purified endo
      inulinase, were used to screen a cDNA library. A 1.7-kb DNA fragment encoding
      endo-inulinase was isolated and analyzed. A single open reading frame, consisting
      of 1548-bp, was found to encode a polypeptide that comprised a 25-amino acid
      signal peptide and 490-amino acid mature protein. All the partial amino acid
      sequences of the purified enzyme were discovered in the deduced ones. The deduced
      amino acid sequences of endo-inulinase had similar sequences to those of fructan
      hydrolases. A 3.5-kb chromosomal DNA fragment encoding endo-inulinase was also
      isolated and analyzed. The same ORF with cDNA clone as identified. There were no
      introns in the endo-inulinase gene.

PMID- 8987854
TI  - Cloning and sequence analysis of a cDNA encoding salmon (Onchorhynchus keta)
      liver transglutaminase.
AB  - We isolated cDNA clones encoding a transglutaminase (TGase: EC 2.3.2.13) from a
      salmon (Onchorhynchus keta) cDNA library prepared from the liver. In the cDNA
      sequence combined, an open reading frame coding for a protein of 680 aa was
      found. The deduced sequence showed a considerable similarity (62.4%) to that of
      red sea bream TGase. By comparison of sequence similarity to other TGases, the
      structure of salmon TGase was like tissue type TGases, rather than membrane
      associated type or plasma type TGases. As a structural feature of salmon TGase, 3
      aa residues were substituted in the 25 aa sequence around the active site Cys
      residue, which is conserved among several tissue type TGases. The critical
      residues thought to form the catalytic-center triad (Cys272, His331, and Asp301)
      were found in the highly conserved region, but the region surrounding Tyr511,
      which corresponds to the residue participates in hydrogen-bond interactions of
      active center domain, was less similar to other TGases, except for red sea bream
      TGase. These finding suggests that the overall structure of fish TGase resembles
      tissue-type TGases, but has some unique structure.

PMID- 8987855
TI  - Two components of cell-bound isopullulanase from Aspergillus niger ATCC 9642-
      their purification and enzymatic properties.
AB  - Cell-bound isopullulanase (pullulan 4-glucanohydrolase: EC 3.2.1.57, IPU) from
      Aspergillus niger ATCC9642 [Y. Sakano et al., Denpun Kagaku, 37, 39-41 (1990)]
      was separated into two active components, IPU F1 (pI = 5.0) and IPU F2 (pI =
      4.9), using a Mono-P HR 5/20 column. The substrate specificity on pullulan and
      panose, specific activity, optimum pH, pH stability, and susceptibility to
      certain chemical reagents were similar between IPU F1 and IPU F2. IPU F1 and F2
      had an identical N-terminal amino acid sequence, A-V-T-A-D-N-S-Q-L-L. However,
      IPU F1 contained more total carbohydrate (15.3%) than IPU F2 (12.4%). SDS
      polyacrylamide gel electrophoresis showed that the molecular weight of IPU F1
      (71,000) was greater than that of IPU F2 (69,000). After deglycosylation of IPU
      F1 and F2 with peptide-N-glycosidase F, the molecular weights of IPU F1 and F2
      became 59,000.

PMID- 8987856
TI  - An alanine racemase gene as a new index for detecting Escherichia coli in foods.
AB  - A gene of alanine racemase, a typical prokaryotic enzyme, was evaluated as a new
      index for detecting Escherichia coli in foods. An alanine racemase gene fragment
      containing a non-conserved sequence of the gene was amplified from genomic DNA of
      E. coli by a polymerase chain reaction, and then labeled with digoxigenin as a
      probe for detecting E. coli. Food samples and bacteria were each treated as at 25
      degrees C for 10 min in 0.1N NaOH containing 0.5% SDS, before being directly
      spotted on to nylon membranes for DNA hybridization. The probe was specific for
      E. coli; all 48 strains of E. coli examined, including such pathogenic strains as
      E. coli O157:H7, showed positive signals, whereas all 59 strains of non-E. coli
      species, except for one strain (Shigella sonnei), did not show a signal. Various
      foods inoculated with E. coli K-12 showed positive signals whereas no
      uninoculated foods showed any signal. Quantification of E. coli cells in the
      death phase by the hybridization method showed good correlation with that by the
      plate culture method. The alanine racemase gene could prove useful as an index
      for detecting E. coli in foods.

PMID- 8987857
TI  - Cis- and trans-linalool 3,7-oxides and methyl salicylate glycosides and (Z)-3
      hexenyl beta-D-glucopyranoside as aroma precursors from tea leaves for oolong
      tea.
AB  - Two new alcoholic aroma precursors, cis- and trans-linalool, 3,7-oxides 6-O-beta
      D-apiofuranosyl-beta-D-glucopyranosides (1 and 2), as well as two already known
      compounds, (Z)-3-hexenyl beta-D-glucopyranoside (3) and methyl salicylate 6-O
      beta-D-xylopyranosyl-beta-D-glucopyranoside (beta-primeveroside: 4), and another
      new monoterpendiol glycoside, 8-hydroxygeranyl beta-primeveroside (5) have
      recently been isolated as aroma precursors in tea leaves (Camellia sinensis var.
      sinensis cv. Maoxie) ready for oolong tea processing.

PMID- 8987859
TI  - Isolation and identification of styrene-degrading Corynebacterium strains, and
      their styrene metabolism.
AB  - By supplying styrene in the gas phase as the sole carbon and energy source,
      styrene-degrading aerobic microorganisms were readily isolated from soil samples.
      They were identified as Corynebacterium pseudodiphtheriticum and similar species,
      or Pseudomonas sp. Growth experiments on some aromatic compounds, resting-cell
      reactions with them, and the measurement of degrading enzyme activities suggest
      that Corynebacterium sp. AC-5 and St-5 strains metabolize styrene through styrene
      oxidation into styrene oxide, then convert it into phenylacetaldehyde by a
      reaction using styrene oxide isomerase, and phenylacetaldehyde is reduced to 2
      phenylethanol. The Corynebacterium sp. ST-10 strain did not have styrene oxide
      isomerase, and metabolized styrene oxide by an unknown enzymatic reaction.
      Possible metabolism of styrene was proposed for the Corynebacterium strains.

PMID- 8987858
TI  - Effects of oxygen and transition metals on the advanced Maillard reaction of
      proteins with glucose.
AB  - The generation of fluorescence and 3-deoxyglucosone (3DG), browning,
      polymerization, and impairment of the amino acid residues of lysozyme incubated
      with glucose were investigated at 37 degrees C and 50 degrees C at pH 7.4 in a
      phosphate or TAPSO buffer under aerobic and non-aerobic conditions with or
      without DETAPAC as a chelating reagent. Browning, the generation of fluorescence,
      and polymerization were accelerated under the non-aerobic, compared to aerobic,
      conditions. Moreover, the formation of 3DG was also significantly increased under
      non-aerobic conditions. The incubation of both reaction systems resulted in
      noticeable losses of arginine and lysine residues. DETAPAC significantly
      inhibited the advanced Maillard reaction under both aerobic and non-aerobic
      conditions. However, DETAPAC had no effect on the impairment of lysine and
      arginine residues. The generation of fluorescence, browning and polymerization of
      lysozyme in the TAPSO buffer were markedly inhibited under both aerobic and non
      aerobic conditions. These observations suggest that transition metals in the
      phosphate buffer may have accelerated the formation of Amadori compounds via
      Schiff's base. In addition, under non-aerobic conditions, the formation of
      advanced glycation end products from 3DG via Amadori compounds is presumed to be
      the major pathway, because the formation of N epsilon-(carboxymethyl)lysine,
      glyoxal, and glucosone was accelerated by an oxidative reaction catalyzed with
      transition metal ions. These presumptions are supported by the results from a
      lysozyme-3DG reaction system.

PMID- 8987860
TI  - Architecture of alkaline-soluble and bioactive polysaccharide from the kernels of
      Prunus mume Sieb. et Zucc. assessed by anti P-1 antibody.
AB  - P-1 was partially hydrolyzed with 0.01, 0.05, and 0.1 M trifluoroacetic acid
      (TFA), successively, and the dialyzable (E-1, E-2, and E-3) and non-dialyzable (I
      1, I-2, and I-3) fractions were prepared and analyzed chemically and
      immunochemically. Either I-1 or E-1 reacted with anti P-1 serum as strongly as P
      1 and were mitogenic. The cross-reactivity of I-2 and I-3 was less than I-1 with
      anti P-1 serum. However, they were as mitogenic as I-1. The cross-reactivity of E
      2 and E-3 to anti P-1 serum was also very weak, and they were not mitogenic. The
      E-1 fraction had a similar sugar composition to I-1 and P-1. E-2 was a
      monosaccharide, all of Ara, and would be from the linkage of furanosyl residues
      in P-1. The composition of E-3 was free from Ara and the structure of E-3 was
      similar to that of I-3. E-3 would be considered to be deleted arabinofuranose
      from E-1. These results suggest that the mitogenic activity measured by the
      alkaline phosphatase assay is a property of the core part, I-3, but that P-1
      contains several epitopes other than the core part by the immunochemical
      analysis.

PMID- 8987861
TI  - Method of obtaining mutants defective in immunoglobulin mu transcription factors.
AB  - A method of obtaining mutants defective in the regulatory function of Ig mu gene
      expression was developed. Such mutants are useful for discovering the functions
      of transcription factors and isolating their genes, especially those of DNA
      unbinding factors. Cells expressing Ig mu and Eco-GPT simultaneously under
      control of each mu enhancer were prepared as follows: myeloma X63Ag8.653 cells
      were transfected with pSV-V mu Me delta CH1 encoding a mu gene modified for cell
      surface mu expression without light chains, selected by neomycin resistance,
      transfected with Eco-GPT gene connected to the mu enhancer, and selected with
      mycophenolic acid in a medium containing xanthine. The mu(m)/Eco-GPT cells were
      mutated with ethane methyl sulfonate (EMS), and selected with toxin-conjugated
      anti-mu antibody, and then with 6-thioguanine. The mu(M)-/Eco-GPT- mutants
      obtained were fused with X63Ag8.653 cells. Fusion caused the mutant to recover
      mu(M) expression, suggesting that some trans-acting transcription factor other
      than the mu-encoding gene itself was probably mutated.

PMID- 8987862
TI  - Structural elucidation of N-liked sugar chains of storage glycoproteins in mature
      pea (Pisum sativum) seeds by ion-spray tandem mass spectrometry (IS-MS/MS).
AB  - The structures of N-linked sugar chains of the storage glycoproteins in mature
      pea seeds have been estimated. Nine pyridylaminated (PA-) N-linked sugar chains
      were derived and purified from the hydrazinolysate of the storage glycoproteins
      by reversed-phase HPLC and size-fractionation HPLC. The structures of the PA
      sugar chains purified were first identified by two-dimensional PA-sugar chain
      mapping, considering the data of sugar composition analysis or sequential
      exoglycosidase digestions. The deduced structures were further analyzed by IS
      MS/MS analysis. Every relevant fragment ion derived from all PA-sugar chains
      could be assigned on the basis of deduced structures. The estimated nine
      structures fell into two categories; the first was a typical oligomannose type
      (Man8-3GlcNAc2; 77.7%) which can be hydrolyzed by endo-beta-N
      acetylglucosaminidase PS [Y. Kimura et al., Biosci. Biotech. Biochem., 60, 228
      232 (1996)], the second was a xylose-containing type (Man4-3Xyl1GlcNAc2,
      Man3Fuc1Xyl1GlcNAc2; 22.3%). Among these structures, Man8GlcNAc2 (19.7%),
      Man6GlcNAc2 (24.7%), and Man3Fuc1Xyl1GlcNAc2 (18.8%) were the dominant
      structures.

PMID- 8987863
TI  - Effects of dietary fats and curcumin on IgE-mediated degranulation of intestinal
      mast cells in brown Norway rats.
AB  - Brown Norway rats were primed intraperitoneally with beta-lactoglobulin for 3 wk
      to induce reaginic antibody, during which time they were fed diets containing 10%
      each of coconut oil (CO), high oleic safflower oil, safflower oil (SO), or fish
      oil, then they were challenged for 3 h orally with the antigen. The dietary SO,
      compared to other dietary fats, resulted in lower circulatory release of rat
      chymaseII (RChyII), an indicator of degranulation of mucosal mast cells in the
      intestine, in response to the antigen. Addition of 0.5% curcumin to the CO or SO
      diet lowered the release. The SO diet, compared to CO diet, tended to increase
      the concentration of reaginic antibody, but the influence of curcumin addition
      was not prominent. These results indicate that dietary ingredients differently
      influence the synthesis of immunoglobulin E and degranulation of mast cells.

PMID- 8987864
TI  - Biodegradability of oxidized poly(vinyl alcohol).
AB  - Poly(vinyl alcohol) dehydrogenase (PVADH) purified from Pseudomonas sp. 113P3
      catalyzed an oxidation of poly(vinyl alcohol) (PVA) in the presence of
      pyrroloquinoline quinone (PQQ) to give a beta-diketone structure on PVA. Although
      PVADH oxidized not only enzymatically oxidized PVA but also chemically oxidized
      PVA, PVA-degrading microorganisms, Pseudomonas sp. 113P3 and Arthrobacter
      tumescens sp. 52-1 grew on the enzymatically oxidized PVA, but not on the
      chemically oxidized PVA. This suggests that the growth of PVA-degrading
      microorganisms is affected by the structure of oxidized PVA.

PMID- 8987865
TI  - Biochemical characteristics of osmophilic yeasts isolated from pollens and honey.
AB  - A total of 1752 strains of osmophilic yeasts were isolated from honey and
      pollens. Forty-three strains of osmophilic yeasts produced polyols, among which 6
      strains produced erythritol in good yields. On the other hand, 52 osmophilic
      yeasts converted sucrose to fructooligosaccharides, among which 8 strains
      produced both extra and intracellular beta-fructofuranosidase, which converted
      sucrose to fructooligosaccharides. This investigation concluded that osmophilic
      yeasts converted sucrose not only to polyols, but also to fructooligosaccharides
      in good yields.

PMID- 8987866
TI  - Lipid composition of commercial bakers' yeasts having different freeze-tolerance
      in frozen dough.
AB  - The lipid composition of some commercial bakers' yeasts having different freeze
      sensitivity in frozen dough was investigated to clarify the correlation between
      their lipid composition and freeze-tolerance. The total lipid content including
      neutral lipid, free fatty acid, sterol, and phospholipid ranged between 23.0 to
      32.2 mg/100 mg protein of the yeasts tested. Phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine were the
      main phospholipids found in all yeast strains, but no distinct difference in
      these components between freeze-tolerant and freeze-sensitive strains was
      observed. Palmitoleic (C16:1), oleic (C18:1), palmitic (16:0), and stearic
      (C18:0) acids were the major fatty acids present in total lipid and phospholipid,
      and unsaturation indices of fatty acid in these lipid components were almost
      equal by the strains. The molar ratios of sterol to phospholipid of freeze
      sensitive strains were higher than those of freeze-tolerant strains. The
      difference in the sterol-phospholipid ratio that influences the fluidity of
      plasma membranes in yeast cells was supposed to reflect the difference in freeze
      sensitivity of bakers' yeast.

PMID- 8987867
TI  - A new and efficient method for gene transfer into mouse FM3A cells using
      metaphase chromosomes by electroporation.
AB  - We introduced chromosome-mediated genes into mouse thymidine kinase-deficient
      FM3A (FM3Atk-) cells, by electroporation. The effects of some parameters on the
      electric shock-mediated transfection of FM3Atk- cells were investigated. Gene
      transfer of mouse L929 metaphase chromosome DNA into FM3Atk- resulted in a
      maximum frequency of (3.0 +/- 0.3) x 10(-5) at a cell density of 2.0 x 10(8)/ml
      and chromosome dosage of 5.0 x 10(7) cell equivalents/ml in a buffer containing
      0.25 M mannitol, 0.5 mM MgCl2, 0.1mM CaCl2, and 1 mM Tris-HCl (pH 7.1). The
      highest yield of the transformants was obtained at an electric field strength of
      1 kV/cm and a capacitance of 35 microF, with a single exponentially decaying
      pulse at 0 degrees C was optimal for post-shock incubation after electroporation.
      The tk gene was detected in the transformants by in situ hybridization analysis.

PMID- 8987868
TI  - Gene cloning and expression of new trehalose-producing enzymes from the
      hyperthermophilic archaeum Sulfolobus solfataricus KM1.
AB  - The genes encoding for trehalose-producing enzymes, a glycosyl-trehalose
      producing enzyme (glycosyltransferase) and a gylcosyl-trehalose-hydrolyzing
      enzyme (alpha-amylase), from Sulfolobus solfataricus KM1 were cloned and
      expressed in E. coli. The nucleotide sequence of the glycosyltransferase gene and
      the alpha-amylase gene indicated proteins with lengths of 728 and 558 amino acids
      and molecular masses of 86-kDa and 65-kDa, respectively. Regions highly conserved
      in the alpha-amylase family exist in the amino acid sequences of these enzymes.

PMID- 8987869
TI  - Effect of reaction temperature on the determination of rat serum IgE by the
      avidin-biotin method.
AB  - We established an avidin-biotin method for the sensitive determination of rat IgE
      and found that a non-specific signal was generated depending on the reaction
      temperature. When the sera of rats immunized or not with ovalbumin (OVA) were
      fractionated in a hydroxyapatite column and OVA-specific IgE was determined by
      the avidin-biotin method at 4 degrees C or 37 degrees C, OVA-specific IgE peaks
      were detected at 37 degrees C, even with nonimmunized rats, but not at 4 degrees
      C.

PMID- 8987870
TI  - Inhibitory effect of arphamenine A on intestinal dipeptide transport.
AB  - Arphamenine A, an Arg-Phe analog without a peptide bond, has been reported to be
      a possible inhibitor of the peptide transporter [H. Daniel and S.A. Adibi, FASEB
      J., 8, 753 (1994)]. The present study demonstrated that arphamenine A is not a
      real inhibitor, but is a substrate for the transporter, being transported
      transepithelially under a proton gradient. The substrate specificity of the
      peptide transporter was wider than expected.

PMID- 8987871
TI  - Intracellular fate of 2-NBDG, a fluorescent probe for glucose uptake activity, in
      Escherichia coli cells.
AB  - A fluorescent derivative of D-glucose, 2-NBDG, which was previously developed for
      the evaluation of glucose uptake activity by living cells, was used on
      Escherichia coli cells and its fate after incorporation in the cells was
      investigated. 2-NBDG was converted to another fluorescent derivative (2-NBDG
      metabolite) immediately after it was taken by E. coli cells. This 2-NBDG
      metabolite was then decomposed to non-fluorescent forms. 2-NBDG metabolite was
      decomposed into the original 2-NBDG by G6Pase with concurrent liberation of
      inorganic phosphate. Furthermore, FAB/MS analysis showed that its molecular
      weight was 420, the same value as that of 2-NBDG 6-phosphate. These indicate 2
      NBDG metabolite should be 2-NBDG 6-phosphate. Based on these results, the
      feasibility of 2-NBDG as a fluorescent non-toxic probe for glucose uptake
      activity and its application to viability assessment of various living systems
      are discussed.

PMID- 8987873
TI  - Substantially complete removal of the 34kDa allergenic soybean protein, Gly m Bd
      30 K, from soy milk of a mutant lacking the alpha- and alpha'-subunits of
      conglycinin.
AB  - Substantially complete removal (99.78%) of the allergenic soybean protein, Gly m
      Bd 30 K, was attained by applying simple centrifugation at 10,000 x g and at pH
      4.5 in the presence of Na2SO4 to defatted soy milk from a genetically mutated
      soybean cultivar (Tohoku 124) which lacked the alpha- and alpha'-subunits of
      conglycinin. The removal rate was ten times higher than that (97.44%) from a
      normal soybean cultivar of I.O.M. grade.

PMID- 8987872
TI  - Cloning and characterization of one member of the chalcone synthase gene family
      from Solanum tuberosum L.
AB  - We have isolated a chalcone synthase gene 2 (ST-CHS2) from potato by rapid
      amplification of cDNA ends by PCR. CHS2 cDNA had high homology to tomato LET-CHS2
      (98%), petunia PHCHSJ (94%), potato ST-CHS1B (92%), petunia PHCHSA (92%), and LET
      CHS1 (90%) at the overall 389-amino acid level. Genomic hybridization analysis
      indicated that CHS genes of potato comprise a family of at least six individual
      members.

PMID- 8987874
TI  - Taste-modifying triterpene glycosides from Staurogyne merguensis.
AB  - Five new oleanane-type triterpene glycosides named strogins 1-5 were isolated
      from leaves of Staurogyne merguensis. Their structures were determined on the
      basis of chemical and spectral evidence. After strogins 1, 2 and 4 were held in
      mouth, water elicited a sweet taste. On the other hand, strogins 3 and 5 had no
      activity. The structure-activity relationship is discussed.

PMID- 8987875
TI  - Infraspecific taxonomy and essential oil chemotypes in sweet basil, Ocimum
      basilicum.
AB  - Essential oil compositions of fresh and freeze-dried leaves were determined for
      16 accessions of Ocimum basilicum belonging to different varieties to see whether
      they could be used as infraspecific taxonomic characters. One accession of O. x
      citriodorum was also studied. Some 30 monoterpenoids, sesquiterpenoids and
      phenylpropanoids were identified, the major components (more than 20% of the
      total essential oil composition in one or more accessions) being geranial and
      neral in O. x citriodorum, and linalool, methyl chavicol, eugenol, methyl eugenol
      and geraniol in O. basilicum. Based on a combination of the latter compounds,
      five major essential oil profiles could be distinguished in the accessions
      studied for O. basilicum. These profiles were largely the same for fresh and
      freeze-dried material of the same plant, although in the dried leaves, methyl
      chavicol and eugenol concentrations had generally declined in comparison to those
      of linalool. There appeared to be little correlation between essential oil
      patterns and varietal classification within O. basilicum. In view of the chemical
      heterogeneity of O. basilicum and its use as an essential oil-producing crop,
      culinary herb, medicinal plant and insect-controlling agent, in all of which
      chemicals play an important role, the infraspecific classification of this taxon
      should take chemical characters into consideration. A system for the
      classification of essential oil chemotypes in O. basilicum is proposed.

PMID- 8987876
TI  - Triterpenoid saponins from Herniaria fontanesii.
AB  - Two new saponins have been isolated from the aerial parts of Herniaria
      fontanesii. Their structures were established as 28-O-[alpha-L-rhamnopyranosyl-(1
      ->2-[(alpha-L- rhamnopyranosyl)-(1-->3)-]-(beta-D-4-acetoxyfucopyranosyl] ester
      of 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl uronic]-2 beta-3
      beta-16-alpha-trihydroxy-olean-12-ene-23, 28-dioic acid and 28-omicron-[alpha-L
      rhamnopyranosyl-(1-->2-[alpha-L-rhamnopyranosyl (1-->3)]-(beta-D-fucopyranosyl]
      ester of 3-omicron-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl uronic]
      2 beta-3 beta-16-alpha-trihydroxy-olean-12-ene-23, 28 dioic acid.

PMID- 8987877
TI  - A flavonoid diglycoside from Lepisorus ussuriensis.

PMID- 8987878
TI  - Two flavonol triglycosides from flowers of Indigofera hebepetala.
AB  - Two new flavonol triglycosides, kaempferol 3-omicron-alpha-L-rhamnopyranosyl(1
      >2)-beta-D-galactopyranoside-7-O- alpha-L-arabinofuranoside and kaempferol 3-O
      alpha-rhamnopyranosyl(1-->6)-beta-D-galactopyranoside-7-O- alpha-L
      arabinofuranoside were isolated from the flowers of Indigofera hepepetala,
      together with three known glycosides, kaempferol 3-omicron-alpha-L
      arabinopyranoside-7-O-alpha-L-rhamnopyranoside, kaempferol 3-O-alpha-L
      rhamnopyranoside-7-O-alpha-L-arabinopyranoside and kaempferol 7-rhamnoside. The
      structures were determined by means of Rf values, UV, EI-mass spectrometry, FAB
      mass spectrometry, 1H NMR, 13C (B.B and DEPT) NMR, NOE difference measurement and
      1H-1H COSY spectral data.

PMID- 8987879
TI  - Secretory production of bioactive recombinant human granulocyte-macrophage colony
      stimulating factor by a baculovirus expression system.
AB  - The proliferation and differentiation of hematopoietic cells are stimulated by a
      group of glycoproteins called colony stimulating factors (CSFs). Previously, we
      found that the human hepatoma cell line HA22T/VGH secreted a high level of human
      granulocyte-macrophage colony-stimulating factor (hGM-CSF). The cDNA of hGM-CSF,
      including the signal peptide sequence, was amplified from the total RNA of
      HA22T/VGH by a reverse-transcription polymerase chain reaction and was cloned
      into the pUC18 vector. After confirming the nucleotide sequence, the cDNA was
      inserted into a pVL1393 baculovirus transfer vector. The recombinant baculovirus
      carrying hGM-CSF cDNA was generated by co-transfecting the hGM-CSF recombinant
      transfer vector and BaculoGold baculovirus DNA into the Sf9 insect cells. The
      expected hGM-CSF transcript was detected in the recombinant virus-infected Sf9
      cells. The conditioned media of the infected cells were analyzed by a slot-blot
      immunoassay. The results indicate that the infected insect cells produced and
      secreted hGM-CSF. According to colony forming assay, a maximum titer of 2.1 x
      10(6). U ml-1 of hGM-CSF in the medium was obtained on the third day after
      infection.

PMID- 8987882
TI  - The inhibitory mechanisms of glucose and carbon dioxide on the biosyntheses of
      penicillins and cephalosporins.
AB  - The inhibitory mechanism of glucose and CO2 on the biosyntheses of penicillins
      and cephalosporins is discussed in the present paper. 6-aminopenicillanic acid (6
      APA) is considered to be an intermediate product, and the reaction between 6-APA
      and glucose may play an important role in the yield and rate of biosyntheses of
      beta-lactam antibiotics. According to this hypothesis the experimental phenomena
      taking place in biosynthesis of penicillin and cephalosporin, such as the
      inhibition by glucose and carbon dioxide and the reduction of the yield, can be
      satisfactorily explained. The stability of 6-aminopenicillanic acid (6-APA) in
      bicarbonate solution, the reaction of 6-APA with sugars, the determination of the
      concentration of the 6-APA-sugar compound and the effect of these reactions on
      the biosynthesis of penicillin G are investigated to present evidences for this
      hypothesis.

PMID- 8987883
TI  - Dielectrophoretic separation of bacteria using a conductivity gradient.
AB  - Dielectrophoresis, the lateral motion induced on particles by non-uniform
      electric fields, is a sensitive function of the electrical conductivity of the
      particle suspending medium. This dependence is exploited in a new technique for
      separating bioparticles from suspended mixtures. The bioparticles are first
      immobilised by positive dielectrophoresis at electrodes in a separation chamber,
      and the conductivity of the liquid flowing through the chamber is then gradually
      and continuously increased so as to produce a conductivity gradient with time.
      The bioparticles are released from the electrodes according to their own
      dielectric properties and as a function of flow rate and medium conductivity.
      This is demonstrated for pure suspensions and mixtures of the bacteria Bacillus
      subtilis, Escherichia coli and Micrococcus luteus.

PMID- 8987884
TI  - Purification and characterization of two low molecular mass alkaline xylanases
      from Fusarium oxysporum F3.
AB  - Two low molecular mass endo-1,4-beta-D-xylanases from Fusarium oxysporum were
      purified to homogeneity by gel-filtration and ion-exchange chromatography. They
      exhibit molecular masses of 20.8 (xylanase I) and 23.5 (xylanase II) kDa, and
      isoelectric points of 9.5 and 8.45-8.70, respectively. Both xylanases display
      remarkable pH (9.0) stability. At 40 to 55 degrees C xylanase II is more
      thermostable than xylanase I but less active on xylan. In contrast to xylanase I,
      xylanase II is able to hydrolyze 1-O-4-methylumbelliferyl-beta-D-glucopyranosyl)
      beta-D-xylopyranoside (muxg). Neither of these enzymes hydrolyze xylotriose. They
      bind on crystalline cellulose but not on insoluble xylan. Analysis of reaction
      mixtures by high pressure liquid chromatography revealed that both enzymes cleave
      preferentially the internal glycosidic bonds of xylopentaose and oat spelts
      xylan. Thus the purified enzymes appeared to be true endo-beta-1,4-xylanases. The
      amino terminal sequences of xylanases I and II show to homology. Xylanase I shows
      high similarity with alkaline low molecular mass xylanases of family G/11.

PMID- 8987885
TI  - Generation of a monoclonal antibody to a defined portion of the Helicobacter
      pylori vacuolating cytotoxin by DNA immunization.
AB  - The capacity of mammalian cells to express proteins encoded by plasmid vectors
      injected as naked DNA has opened the possibility to induce an immune response
      against protein antigens by DNA vaccination. We have used DNA immunization to
      generate a strong antibody response to a defined portion of the Helicobacter
      pylori vacuolating cytotoxin. A high specific monoclonal antibody has been
      derived from the splenocytes of an immunized mouse. Our data show that DNA
      immunization offers the possibility to obtain monoclonal antibodies following a
      significant shortcut with respect to traditional immunization protocols.

PMID- 8987886
TI  - Removal of Cr(VI) from ground water by Saccharomyces cerevisiae.
AB  - Chromium can be removed from ground water by the unicellular yeast, Saccharomyces
      cerevisiae. Local ground water maintains chromium as CrO42- because of
      bicarbonate buffering and pH and Eh conditions (8.2 and +343 mV, respectively).
      In laboratory studies, we used commercially available, nonpathogenic S.
      cerevisiae to remove hexavalent chromium [Cr(VI)] from ground water. The
      influence of parameters such as temperature, pH, and glucose concentration on
      Cr(VI) removal by yeast were also examined. S. cerevisiae removed Cr(VI) under
      aerobic and anaerobic conditions, with a slightly greater rate occurring under
      anaerobic conditions. Our kinetic studies reveal a reaction rate (Vmax) of 0.227
      mg h-1 (g dry wt biomass)-1 and a Michaelis constant (Km) of 145 mg/l in natural
      ground water using mature S. cerevisiae cultures. We found a rapid (within 2
      minutes) initial removal of Cr(VI) with freshly hydrated cells [55-67 mg h-1 (g
      dry wt biomass)-1] followed by a much slower uptake [0.6-1.1 mg h-1 (g dry wt
      biomass)-1] that diminished with time. A materials-balance for a batch reactor
      over 24 hours resulted in an overall shift in redox potential from +321 to +90
      mV, an increase in the bicarbonate concentration (150-3400 mg/l) and a decrease
      in the Cr(VI) concentration in the effluent (1.9-0 mg/l).

PMID- 8987887
TI  - Spectroscopic and elemental investigation of microbial decomposition of aquatic
      fulvic acid in biological process of drinking water treatment.
AB  - As humic substances left in treated water tend to form trihalomethans during
      chlorination, their removal in water treatment processes is a significant concern
      for drinking water supplies. One of the removal technologies, the biofilm reactor
      is studied for the microbial decomposition of aquatic fulvic acid (AFA). The AFA
      is characterized by elemental analysis. UV-Vis, 13C-NMR, and IR spectroscopic
      methods. The spectroscopic and elemental investigation was capable of
      characterizing the microbial decomposition of AFA. Biologically treated fulvic
      acid was in a more oxidized state; its spectra displayed a higher degree of
      condensation of aromatic constituents than influent fulvic acid. Microbial
      degradation of AFA was more active in the low molecular weight fractions and
      intensively occurred in the aliphatic fraction.

PMID- 8987888
TI  - Bacterial influence on partitioning rate during the biodegradation of styrene in
      a biphasic aqueous-organic system.
AB  - The degradation by a consortium of slightly-halophile marine bacteria of styrene
      initially dissolved in silicone oil was monitored in batch reactors stirred at
      75, 125 and 500 rpm, respectively. In the 75 and 125 rpm cases, the styrene
      biodegradation rate was higher than the rate of spontaneous partitioning of
      styrene from the oil to the water, determined under abiotic conditions. Abiotic
      transfer tests carried out after biodegradation runs revealed that bacterial
      activity had resulted in a significant increase in the rate of styrene
      partitioning between the two liquid phases. Even though bacterial adsorption was
      noticeable at the oil-water interface, this effect appeared to be due to the
      release by the bacteria of chemicals in the aqueous phase. Similarity with
      observations made with Triton X-100 suggested that the chemicals released may
      have been biosurfactants or solubilizing agents.

PMID- 8987889
TI  - Degradation of 3-nitrophenol by Pseudomonas putida B2 occurs via 1,2,4
      benzenetriol.
AB  - Growth of Pseudomonas putida B2 in chemostat cultures on a mixture of 3
      nitrophenol and glucose induced 3-nitrophenol and 1,2,4-benzenetriol-dependent
      oxygen uptake activities. Anaerobic incubations of cell suspensions with 3
      nitrophenol resulted in complete conversions of the substrate to ammonia and
      1,2,4-benzenetriol. This indicates that P. putida B2 degrades 3-nitrophenol via
      1,2,4-benzenetriol, via a pathway involving a hydroxylaminolyase. Involvement of
      this pathway in nitroaromatic metabolism has previously only been found for
      degradation of 4-nitrobenzoate. Reduction of 3 nitrophenol by cell-free extracts
      was strictly NADPH-dependent. Attempts to purify the enzymes responsible for 3
      nitrophenol metabolism were unsuccessful, because their activities were extremely
      unstable. 3-Nitrophenol reductase was therefore characterized in cell-free
      extracts. The enzyme had a sharp pH optimum at pH 7 and a temperature optimum at
      25 degrees C. At 30 degrees C, reductase activity was completely destroyed within
      one hour, while at 0 degrees C, the activity in cell-free extracts was over 100
      fold more stable. The Km values for NADPH and 3-nitrophenol were estimated at
      0.17 mM and below 2 microM, respectively. The substrate specificity of the
      reductase activity was very broad: all 17 nitroaromatics tested were reduced by
      cell-free extracts. However, neither intact cells nor cell-free extracts could
      convert a set of synthesized hydroxylaminoaromatic compounds to the corresponding
      catechols and ammonia. Apparently, the hydroxylaminolyase of P. putida B2 has a
      very narrow substrate specificity, indicating that this organism is not a
      suitable biocatalyst for the industrial production of catechols from
      nitroaromatics.

PMID- 8987890
TI  - Biodegradation of rubber particles in soil.
AB  - The biodegradation of rubber particles in rubber-soil mixtures at different
      rubber contents was monitored by the carbon dioxide production. The cumulative
      carbon dioxide production was modelled according to a two parameter exponential
      function. The model provides an excellent fit (R2 > 0.98) for the observed data.
      The two parameters yield a reliable estimate of the half-life for the process
      observed, but estimation of the true half-life of rubber in soil will need more
      research.

PMID- 8987891
TI  - Changes in mutagenicity during crude oil degradation by fungi.
AB  - Two fungal strains, Cunninghamella elegans and Penicillium zonatum, that grow
      with crude oil as a sole carbon source were exposed to three crude oils that
      exhibit a range of mutagenic activity. At regular time intervals following fungal
      incubation with the various crude oils, extracts were tested for the presence of
      mutagenic activity using the spiral Salmonella assay. When the most mutagenic of
      the oils, Pennsylvania crude oil, was degraded by C. elegans or by P. zonatum,
      its mutagenicity was significantly reduced; corresponding uninoculated
      (weathered) controls of Pennsylvania crude remained mutagenic. West Texas Sour
      crude oil, a moderately mutagenic oil, exhibited little change in mutagenicity
      when incubated with either C. elegans or P. zonatum. Swanson River Field crude
      oil from Cook Inlet, Alaska is a slightly mutagenic oil that became more
      mutagenic when incubated with C. elegans; weathered controls of this oil showed
      little change in mutagenicity. Mycelial mat weights measured during growth on
      crude oils increased corresponding to the biodegradation of about 25% of the
      crude oil.

PMID- 8987892
TI  - Anaerobic degradation of phthalic acid esters during digestion of municipal solid
      waste under landfilling conditions.
AB  - Anaerobic microorganisms in municipal solid waste samples from laboratory-scale
      landfill reactors and a pilot-plant biogas digestor were investigated with the
      aim of assessing their ability to transform four commercially used phthalic acid
      esters (PAEs) and phthalic acid (PA). The PAEs studied were diethyl phthalate
      (DEP), butylbenzyl phthalate (BBP), dibutyl phthalate (DBP) and bis(2-ethylhexyl)
      phthalate (DEHP). No biological transformation of DEHP could be detected in any
      of the experiments. Together with waste samples from the simulated landfilling
      conditions, the PAEs (except DEHP) were hydrolytically transformed to their
      corresponding monoesters. These accumulated as end products, and in most cases
      they were not further degraded. During incubation with waste from the biogas
      digestor, the PAEs (except DEHP) were completely degraded to methane and carbon
      dioxide. The influence of the landfill development phase on the transformations
      was investigated utilizing PA and DEP as model substances. We found that during
      both the intense and stable methanogenic (but not the acidogenic) phases, the
      microorganisms in the samples had the potential to transform PA. A shorter lag
      phase was observed for the PA transformation in the samples from the stable
      methanogenic phase as compared with earlier phases. This indicates an increased
      capacity to degrade PA during the aging phases of the municipal solid waste in
      landfills. No enhancement of the DEP transformation could be observed as
      conditions in the methanogenic landfill model changed over a year's time. The
      results indicate that microorganisms developing in a methanogenic landfill
      environment have a substantially lower potential to degrade compared with those
      developing in a biogas reactor.

PMID- 8987894
TI  - Cyanobacteria carrying an smt-lux transcriptional fusion as biosensors for the
      detection of heavy metal cations.
AB  - The metal-responsive smt operator/promoter region of Synechococcus PCC7942 was
      fused to the luxCDABE genes of Vibrio fischeri. Plasmid DNA (pJLE23) carrying
      this fusion conferred metal ion-inducible luminescence to transformed
      cyanobacteria. Synechococcus PCC7942 (pJLE23) was sensitive to ZnCl2
      concentrations within a range of 0.5-4 microM as demonstrated by induction of
      luminescence. Trace levels of CuSO24 and CdCl2 were also detected.

PMID- 8987893
TI  - Transposon and spontaneous deletion mutants of plasmid-borne genes encoding
      polycyclic aromatic hydrocarbon degradation by a strain of Pseudomonas
      fluorescens.
AB  - Pseudomonas fluorescens strain LP6a, isolated from petroleum condensate
      contaminated soil, utilizes the polycyclic aromatic hydrocarbons (PAHs)
      naphthalene, phenanthrene, anthracene and 2-methylnaphthalene as sole carbon and
      energy sources. The isolate also co-metabolically transforms a suite of PAHs and
      heterocycles including fluorene, biphenyl, acenaphthene, 1-methylnaphthalene,
      indole, benzothiophene, dibenzothiophene and dibenzofuran, producing a variety of
      oxidized metabolites. A 63 kb plasmid (pLP6a) carries genes encoding enzymes
      necessary for the PAH-degrading phenotype of P. fluorescens LP6a. This plasmid
      hybridizes to the classical naphthalene degradative plasmids NAH7 and pWW60, but
      has different restriction endonuclease patterns. In contrast, plasmid pLP6a
      failed to hybridize to plasmids isolated from several phenanthrene-utilizing
      strains which cannot utilize naphthalene. Plasmid pLP6a exhibits reproducible
      spontaneous deletions of a 38 kb region containing the degradative genes. Two
      gene clusters corresponding to the archetypal naphthalene degradation upper and
      lower pathway operons, separated by a cryptic region of 18 kb, were defined by
      transposon mutagenesis. Gas chromatographic-mass spectrometric analysis of
      metabolites accumulated by selected transposon mutants indicates that the
      degradative enzymes encoded by genes on pLP6a have a broad specificity permitting
      the oxidation of a suite of polycyclic aromatic and heterocyclic substrates.

PMID- 8987895
TI  - A comparison of carbon/energy and complex nitrogen sources for bacterial sulphate
      reduction: potential applications to bioprecipitation of toxic metals as
      sulphides.
AB  - Detailed nutrient requirements were determined to maximise efficacy of a sulphate
      reducing bacterial mixed culture for biotechnological removal of sulphate,
      acidity and toxic metals from waste waters. In batch culture, lactate produced
      the greatest biomass, while ethanol was more effective in stimulating sulphide
      production and acetate was less effective. The presence of additional bicarbonate
      and H2 only marginally stimulated sulphide production. The sulphide output per
      unit of biomass was greatest using ethanol as substrate. In continuous culture,
      ethanol and lactate were used directly as efficient substrates for sulphate
      reduction while acetate yielded only slow growth. Glucose was utilised following
      fermentation to organic acids and therefore had a deleterious effect on pH.
      Ethanol was selected as the most efficient substrate due to cost and efficient
      yield of sulphide. On ethanol, the presence of additional carbon sources had no
      effect on growth or sulphate reduction in batch culture but the presence of
      complex nitrogen sources (yeast extract or cornsteep) stimulated both. Cornsteep
      showed the strongest effect and was also preferred on cost grounds. In continuous
      culture, cornsteep significantly improved the yield of sulphate reduced per unit
      of ethanol consumed. These results suggest that the most efficient nutrient
      regime for bioremediation using sulphate-reducing bacteria required both ethanol
      as carbon source and cornsteep as a complex nitrogen source.

PMID- 8987896
TI  - Differential killer sensitivity as a tool for fingerprinting wine-yeast strains
      of Saccharomyces cerevisiae.
AB  - The extreme variability of the killer phenomenon in nature, expressed differently
      in different strains of the same yeast species, embodies an exceptional potential
      for the discrimination of yeasts at the strain level. Killer-sensitive
      relationships between a killer reference panel of 24 yeasts belonging to 13
      species of six genera, and different industrial wine-starters of Saccharomyces
      cerevisiae can be used profitably for a rapid and simple fingerprinting
      procedure.

PMID- 8987897
TI  - Proteolytic activity of lactobacilli in a model goats' milk curd system.
AB  - Mesophyllic lactobacilli cultures propagated in MRS broth were inoculated in
      goats' milk curd slurries and incubated at 30 degrees C for 10 d. The micro
      organisms tested were Lactobacillus casei subsp. casei IFPL 731 and IFPL 99, and
      Lactobacillus plantarum IFPL 3. Whole cells, cell-free extracts and cell lysates
      were evaluated for acceleration of proteolysis in the curd slurries. Conversion
      of water-soluble nitrogen to non-protein nitrogen and amino acid nitrogen,
      reverse phase-HPLC peak areas and ratio of hydrophobic to hydrophilic peptides,
      were all affected by the type of inoculum used as well as the strain under study.
      The results suggest that the accelerated-ripening model system developed,
      containing cell lysates, may be suitable as a good and rapid indicator of the
      contribution of the strains to proteolysis during cheese ripening.

PMID- 8987898
TI  - Rapid GC analysis of cellular fatty acids for characterizing Lactobacillus sake
      and Lact. curvatus strains of meat origin.
AB  - A rapid procedure based on the gas chromatographic analysis of cellular fatty
      acids was used to differentiate between strains of Lactobacillus sake and Lact.
      curvatus isolated from dry salami. All strains had very similar fatty acid
      profiles except four of them which lacked C19 cycl acid, but neither this feature
      nor other differences in single fatty acid contents could be successfully
      correlated with the biochemical discrimination of Lact. sake from Lact. curvatus.
      When, however, strains were compared on the basis of the total content of fatty
      acids with 18 carbon atoms divided by that with 16 carbon atoms, a very good
      correlation with strain characterization by classical methods was achieved. It
      was concluded that selected cellular fatty acids ratios might be useful for
      characterizing phylogenetically related strains of lactic acid bacteria.

PMID- 8987899
TI  - The cryopreservation of some large ciliate entodiniomorphid protozoa taken from
      the rumen.
AB  - Large entodiniomorphid ciliates taken from the rumen cannot be reliably kept in
      vivo, and cryopreservation was investigated as an alternative approach to
      storage. Three species of large entodiniomorphid ciliated (Polyplastron
      multivesiculatum, Epidinium ecaudatum forma caudatum and Ophryoscolex caudatus
      forma tricoronatus) were cryopreserved by one-step freezing, with mean recoveries
      of 43, 51 and 80%, respectively. For Ophryoscolex caudatus forma tricoronatus two
      step freezing was investigated. The mean recovery was 30%, and of tested
      parameters, the equilibration time and temperature of the cryoprotective additive
      of dimethyl sulphoxide and the length of holding phase at -40 degrees C were
      found to be critical for the success of the method.

PMID- 8987900
TI  - Physiological response of Enterococcus faecalis JH2-2 to cold shock: growth at
      low temperatures and freezing/thawing challenge.
AB  - Growth at low positive temperatures and induced phenotypic resistance to extreme
      cold temperature (freezing/thawing cycles) of Enterococcus faecalis were
      investigated. The effect of low temperatures on the specific growth rates was
      studied; use of Arrhenius profile and Ratkovsky 'square-root' model allowed
      determination of the 'temperature characteristic' (mu approximately equal to
      13,800 cal mol-1), the critical temperature (Tcrit approximately equal to 17.9
      degrees C) and the notional minimum growth temperature (T0 approximately equal to
      3.6 degrees C). Preincubation of Ent. faecalis cells at low temperatures (8-16
      degrees C) during periods corresponding to their generation time resulted in an
      increased ability of the bacterial cells to withstand short periods of
      freezing/thawing (-20 degrees C/+37 degrees C) challenge. Moreover, the increase
      of the incubation period at low positive temperature led to a higher degree of
      adaptation.

PMID- 8987901
TI  - Purification and characterization of glucoamylase produced by Aspergillus niger
      in solid state fermentation.
AB  - Glucoamylases produced by Aspergillus niger grown on wheat brain in solid
      cultures were purified. Four different forms, GA I, GA I', GA II and GA III, were
      found having apparent molecular weights of 112,000, 104,000, and 74,000 and
      61,000 Da respectively. The enzymes are glycoproteins with a carbohydrate content
      of 16%, and optimal activity at 60 degrees C and pH 4.4. Activity was strongly
      inhibited by Hg2+ while Mn2+ and Fe2+ were stimulatory. The Km values for the
      degradation of starch and maltose were 3.5 and 7.8 mg ml-1, respectively.

PMID- 8987902
TI  - The role of ciliate protozoa in the lysis of methanogenic archaea in rumen fluid.
AB  - Predation by ciliate protozoa can account for 90% of the eubacterial protein
      turnover in the rumen. However, little is known about the factors affecting the
      lysis of archaea in rumen fluid. Bacterial lysis was followed from the release of
      acid-soluble 14C from 14C leucine-labelled bacteria. The rumen methanogen
      Methanobrevibacter MF1 was broken down more rapidly than other non-ruminal
      archaea in rumen fluid withdrawn from sheep harbouring either a mixed protozoa
      population or monofaunated with Polyplastron multivesiculatum or Entodinium spp.
      The removal of protozoa from the rumen fluid had little effect on the breakdown
      of Methanobrevibacter, while lysis of the non-methanogenic ruminal bacterium
      Selenomonas ruminantium decreased by over 70%. Substantial lysis of
      Methanobrevibacter occurred in cell-free rumen fluid and this effect could be
      abolished by autoclaving. In view of the high number of bacteriophages in rumen
      fluid and susceptibility of ruminal bacteria to phage-induced lysis it is
      tempting to suggest that phages have a role in the lysis of archaea in rumen
      fluid.

PMID- 8987903
TI  - Genetic relatedness amongst intestinal spirochaetes isolated from rats and birds.
AB  - Multilocus enzyme electrophoresis was used to determine genetic relationships
      amongst 32 intestinal spirochaetes (Serpulina spp.) isolated from rats (17),
      rheas (7), chickens, (4), ducks (2), a swan (1) and a flamingo (1). The strains
      were divided into 20 electrophoretic types (ETs), with a mean genetic diversity
      per locus of 0.62. The results were compared with those previously published for
      porcine intestinal spirochaetes. One strain from a healthy rat, and three rhea
      strains which were recovered from cases of necrotizing typhlitis, were grouped in
      the same ETs as certain porcine strains of Serpulina hyodysenteriae. The rhea
      strains could be differentiated from these by pulsed-field gel electrophoresis.
      Fifteen of the rat strains were genetically and phenotypically closely related.
      In contrast the avian strains were genetically more heterogeneous, with
      pathogenic isolates located in three different genetic groups.

PMID- 8987904
TI  - Characterization of a stable L-form of the fish pathogen Aeromonas salmonicida.
AB  - A stable L-form of Aeromonas salmonicida, which resulted from induction with
      benzylpenicillin, contained more of an outer membrane protein, with an estimated
      molecular weight of 40 kDa but less of 47.9 and 38 kDa proteins, than did
      parental walled cells. In addition, from Western blots, two protein bands reacted
      strongly with a polyclonal antiserum. The antiserum did not react demonstrably
      with the band detected in the L-forms on the gels.

PMID- 8987905
TI  - Characteristics of maltose transporter activity in an ale and large strain of the
      yeast Saccharomyces cerevisiae.
AB  - Kinetic studies on maltose uptake by ale and larger yeasts showed lower Km and
      higher Vmax values than for laboratory yeasts. Eadie-Hofstee plots were biphasic
      and inhibition by sulphydryl reagents was consistent with low affinity uptake by
      a specific transporter rather than by non-specific adsorption. High affinity
      maltose transport by both strains was inhibited by galactose, CCCP, 2, 4,-DNP and
      NEM. In contrast, glucose and pCMBS inhibited high affinity transport by the ale
      yeast but not by the larger yeast. In the case of pCMBS the difference could
      result from a single amino acid change in the maltose transporter.

PMID- 8987906
TI  - Elicitation of dihydrobenzophenanthridine oxidase in Sanguinaria canadensis cell
      cultures.
AB  - Dihydrobenzophenanthridine (DHBP) oxidase catalyses the last step in the
      biogenesis of the benzo[c]phenanthridine alkaloid sanguinarine. Addition of
      autoclaved fungal preparations or putative plant defence signalling intermediates
      (jasmonic acid (JA), methyl jasmonate (MeJ), acetylsalicylic acid (ASA)) to
      Sanguinaria canadensis cell suspension cultures elicited an increase in the
      activity of DHBP oxidase. MeJ and ASA were better inducers of oxidase activity
      than were the fungal elicitor and JA. Enzyme-specific activity could be induced
      in a dose- and time-dependent manner up to 4- to 14-fold, respectively, when
      cells were treated with MeJ or with ASA. A change in total enzyme activity in
      cultured cells was observed only at the highest concentration of MeJ and not at
      any level of ASA tested. The results suggest that MeJ and ASA may play a role in
      the S. canadensis defence against pathogens by eliciting the enzymes involved in
      the synthesis of the phytoalexin benzophenanthridine alkaloids.

PMID- 8987907
TI  - Structural characterization of 15-hydroxytrichodiene, a sesquiterpenoid produced
      by transformed tobacco cell suspension cultures expressing a trichodiene synthase
      gene from Fusarium sporotrichioides.
AB  - Tobacco (Nicotiana tabaccum) cell suspension cultures transformed with a gene
      encoding trichodiene synthase, a sesquiterpene synthase from the fungus Fusarium
      sporotrichioides, produced a novel sesquiterpenoid derived from the in vivo
      production of trichodiene. Mass and nuclear magnetic resonance spectroscopic
      analyses identified the new compound as 15-hydroxytrichodiene. The in vivo
      hydroxylation of trichodiene by transformant tobacco cell suspension cultures
      demonstrates that the introduction of a foreign sesquiterpene synthase gene can
      result in the production of novel sesquiterpenoid metabolites.

PMID- 8987908
TI  - Triterpene alcohols from the flowers of compositae and their anti-inflammatory
      effects.
AB  - Eleven tabular and nine ligulate flowers from 15 species of Compositae plants
      were investigated for their triterpene alcohol constituents. This led to the
      isolation and identification of 11 triterpene alcohols as follows: heliaol,
      taraxasterol, psi-taraxasterol, alpha-amyrin, beta-amyrin, lupeol, taraxerol,
      cycloartenol, 24-methyl-enecycloartanol, tirucalla-7,24-dienol and dammaradienol.
      The tabular flowers of Calendula officinalis, Carthamus tinctorius, Cosmos
      bipinnatus, Chrysanthemum morifolium, Helianthus annuus and Matricaria
      matricarioides showed a characteristic feature by containing helianol as the most
      predominant component (29-86%) in the triterpene alcohol fractions. The
      triterpene alcohols from Compositae flowers were evaluated with respect to their
      anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate-induced
      inflammation (1 microgram per ear) in mice. All of these showed marked inhibitory
      activity, and their 50% inhibitory dose was 0.1-0.8 mg per ear.

PMID- 8987909
TI  - Hydroxycinnamoyl ester glycosides and saponins from flowers of Verbascum
      phlomoides.
AB  - A new iridoid ester glycoside acylated with p-coumaric acid was isolated from the
      flowers of Verbascum phlomoides, together with one known one, specioside. Caffeic
      acid esters, verbascoside and forsythoside B were found as minor constituents. A
      new saponin was also obtained and identified as desrhamnosylverbascosaponin.

PMID- 8987910
TI  - Triterpenes from the combined leaf and stem of Lithospermum caroliniense.
AB  - An investigation of the combined leaf and stem of Lithospermum caroliniense
      afforded two new pentacyclic triterpenoids based on the olean-12-ene and taraxast
      12-ene skeletal types. The structures of these compounds were elucidated on the
      basis of spectral analysis as 1 alpha,3 beta,23-trihydroxyolean-12-ene-28-oic
      acid and 3 alpha,19 beta,21 alpha,23-tetrahydroxytaraxast-12-ene-28-oic acid.

PMID- 8987911
TI  - Steroidal saponins from Sansevieria trifasciata.
AB  - The methanol extract of the whole plant of Sansevieria trifasciata has yielded 12
      steroidal saponins, 10 of which are new constituents. The respective structures
      of the new compounds have been shown by the spectroscopic evidence, and alkaline-
      and acid-catalysed degradation. This is the first report of the isolation of
      steroidal saponins from S. trifasciata.

PMID- 8987912
TI  - Acylated pelargonidin glycosides in red-purple flowers of Ipomoea purpurea.
AB  - Four acylated pelargonidin glycosides were isolated from the red-purple flowers
      of Ipomoea purpurea. The acylated anthocyanins were all based on pelargonidin 3
      sophoroside-5-glucoside, acylated with caffeic acid and/or glucosylcaffeic acids.
      Three novel anthocyanins were elucidated to be pelargonidin 3-O-[2-O-(6-O-(trans
      3-O-(beta-D-glucopyranosyl)-caffeyl)- beta-D-glucopyranosyl)-6-O-(trans-4-O-(6-O
      (trans-caffeyl)-beta-D- glucopyranosyl)-caffeyl)-beta-D-glucopyranoside]-5-O-
      [beta-D-glucopyranoside], pelargonidin 3-O-[2-O-(6-O-(trans-caffeyl)-beta-D
      glucopyranosyl)-6-O- (trans-4-O-(6-O-(trans-caffeyl)-beta-D-glucospyranosyl)
      ceffeyl )-beta-D- glucopyranoside]-5-O-[beta-D-glucopyranoside] and pelargonidin
      3-O[2-O-(2-O-(6-O-(trans-caffeyl)-beta-D-glucopyranosyl)-6-O- (trans-caffeyl)
      beta-D-glucopyranoside]-5-O-[beta-D-glucopyoside]. Another anthocyanin was
      pelargonidin 3-O-[2-O-(glucosylcaffeylglucosyl)-6-O-(caffeyl)-glucoside]-5-gluc
      oside, which was reported to be present in the red-purple flowers of Pharbitis
      nil. Apart from the second pigment cited, these are analogous pigments of the
      violet-blue Ipomoea anthocyanins which are composed of acylated cyanidin
      glycosides, instead of pelargonidin.

PMID- 8987913
TI  - Genetic manipulation of mosquitoes: an approach to controlling disease.

PMID- 8987914
TI  - Fishing the best pool for novel ribozymes.
AB  - Novel RNA enzymes, or ribozymes, are sought in large pools of random RNA
      sequences. Because of the large number of random positions in an individual pool
      molecule, only a vanishingly small fraction of the possible sequences are
      actually present. Even so, increasing the length of the individual pool molecules
      significantly increases the probability of finding a particular complex ribozyme.
      Because ribozymes are typically composed of conserved sequences interleaved with
      regions that can vary in sequence and length, a longer molecule allows a greater
      number of possible arrangements of a given ribozyme motif, increasing the
      likelihood that it will be present in the pool. Once a ribozyme motif has been
      found, rational and irrational optimization techniques can be used to identify
      related ribozyme sequences with greater activity.

PMID- 8987915
TI  - Biophysical methods for the determination of antibody-antigen affinities.
AB  - Binding specificities against virtually any antigen can be isolated from antibody
      libraries displayed on filamentous phage. The determination of antibody-antigen
      affinity constants and binding kinetics is an important part of antibody
      characterization, and may be predictive of antibody performance in
      biotechnological applications. This article, intended as a guideline for the
      scientist who isolates a novel antibody and wishes to characterize its binding
      properties, presents the authors' view on widely used methodologies for the
      quantitative determination of antibody-antigen interactions.

PMID- 8987916
TI  - Automation of selective assays for on-line bioprocess monitoring by flow
      injection analysis.
AB  - On-line analysis of one component in a complex media used for bioprocesses
      requires the application of selective tests such as enzymes assays. Because these
      assays are susceptible to interference by other medium components and have a
      limited detection range, automatic sample pretreatment is a prerequisite. The
      progress made with automatic sample pretreatment in flow-injection analysis makes
      this technique particularly suitable for on-line monitoring of bioprocesses.
      Moreover, newly developed software control systems may improve the necessary
      robustness of flow-infection analysis systems.

PMID- 8987917
TI  - The future of PCR technology: diversification of technologies and applications.
AB  - The polymerase chain reaction has had a major impact on research in molecular
      biology, on the human genome project and on the diagnosis of disease. In the
      future, this powerful technique will be increasingly applied to the study of
      individual genomic variation and to assess the genetic consequences of ecological
      and demographic events on past and contemporary populations of many organisms.

PMID- 8987918
TI  - For what we stand.

PMID- 8987919
TI  - Vaginal versus abdominal reconstructive surgery for the treatment of pelvic
      support defects: a prospective randomized study with long-term outcome
      evaluation.
AB  - OBJECTIVES: Our purpose was to determine whether a vaginal or abdominal approach
      is more effective in correcting uterovaginal prolapse. STUDY DESIGN: Eighty-eight
      women with cervical prolapse to or beyond the hymen or with vaginal vault
      inversion > 50% of its length and anterior vaginal wall descent to or beyond the
      hymen were randomized to a vaginal versus abdominal surgical approach. Forty
      eight women underwent a vaginal approach with bilateral sacrospinous vault
      suspension and paravaginal repair, and 40 women underwent an abdominal approach
      with colposacral suspension and paravaginal repair. Ancillary procedures were
      performed as indicated. Detailed pelvic examination was performed postoperatively
      by the nonsurgeon coauthor yearly up to 5 years. The women were examined while
      standing during maximum strain. Surgery was classified as optimally effective if
      the woman remained asymptomatic, the vaginal apex was supported above the levator
      plate, and no protrusion of any vaginal tissue beyond the hymen occurred.
      Surgical effectiveness was considered unsatisfactory if the woman was
      symptomatic, the apex descended > 50% of its length, or the vaginal wall
      protruded beyond the hymen. RESULTS: Eighty women (vaginal 42, abdominal 38) were
      available for evaluation at 1 to 5.5 years (mean 2.5 years). The groups were
      similar in age, weight, parity, and estrogen status, and 56% had undergone prior
      pelvic surgery. There was no significant difference between the groups in
      morbidity, complications, hemoglobin change, dyspareunia, pain, or hospital stay.
      The vaginal group had longer catheter use, more urinary tract infections, more
      incontinence, decreased operative time, and lower hospital charge. Surgical
      effectiveness was optimal in 29% of the vaginal group and 58% of the abdominal
      group and was unsatisfactory leading to reoperation in 33% of the vaginal group
      and 16% of the abdominal group. The reoperations included procedures for
      recurrent incontinence in 12% of the vaginal and 2% of the abdominal groups. The
      relative risk of optimal effectiveness by the abdominal route is 2.03 (95%
      confidence interval 1.22 to 9.83), and the relative risk of unsatisfactory
      outcome using the vaginal route is 2.11 (95% confidence interval 0.90 to 4.94).
      CONCLUSIONS: Reconstructive pelvic surgery for correction of significant pelvic
      support defects was more effective with an abdominal approach.

PMID- 8987920
TI  - Pelvic support defects and visceral and sexual function in women treated with
      sacrospinous ligament suspension and pelvic reconstruction.
AB  - OBJECTIVE: Our purpose was to evaluate the efficacy and consequences of
      sacrospinous ligament suspension and pelvic reconstruction. STUDY DESIGN:
      Patients who underwent sacrospinous ligament suspension between 1978 and 1991
      were evaluated from follow-up visits, telephone interviews, questionnaires, and
      chart reviews. Before and after operation, vaginal support was graded in three
      segments. Postoperative visceral and sexual function was evaluated. RESULTS: Mean
      length of follow-up for 243 patients was 73.6 months. Of these, 102 (42.0%) had a
      support defect in at least one segment; anterior, posterior, and apical defects
      were found in 91 (37.4%), 33 (13.6%), and 20 (8.2%) patients, respectively. A
      clinically significant defect was defined as a symptomatic first-degree or any
      second-or third-degree prolapse. Defect-free survival rates at 1, 5, and 10 years
      were 88.3%, 79.7%, and 51.9%, respectively. Eleven patients (4.5%) underwent
      subsequent pelvic reconstruction. CONCLUSION: Sacrospinous ligament suspension
      and pelvic reconstruction are effective for vaginal apex support, but vaginal
      prolapse recurs with time, most commonly in the anterior segment.

PMID- 8987921
TI  - Hysterectomy after endometrial ablation.
AB  - OBJECTIVES: Our purpose was to determine the number of women undergoing
      hysterectomy after endometrial ablation and the indications for the subsequent
      surgery. STUDY DESIGN: Forty-two premenopausal women, who had severe menorrhagia
      associated with a clinically normal examination result, underwent rollerball
      endometrial ablation between November 1990 and December 1991. Thirty-seven women
      whom we gave ongoing care were evaluated by chart review. Four women who received
      care elsewhere were interviewed by telephone. One woman was lost to follow-up.
      Patients were followed up a minimum of 4 years. Age, parity, operating time,
      endometrial preparation, preablation sterilization, and preablation dysmenorrhea
      were assessed in regard to subsequent hysterectomy. Patient satisfaction was
      assessed at 24 months. Life-table analysis was performed to determine cumulative
      probability of hysterectomy. RESULTS: Fourteen of the 41 women (34%) underwent
      hysterectomy within 5 years after rollerball endometrial ablation. Continued
      abnormal menstrual bleeding and menstrual pain were significantly associated with
      subsequent hysterectomy. Eleven of the 14 cases of hysterectomy were associated
      with gross abnormality such as myomas, adenomyosis, endometriosis, and chronic
      hematosalpinx. A linear relationship between hysterectomy and time was noted.
      CONCLUSION: On the basis of our findings one third of women undergoing rollerball
      endometrial ablation for menorrhagia can expect to have a hysterectomy within 5
      years. If the linear relationship noted during the first 5 years is extrapolated,
      theoretically, all women may need hysterectomy by 13 years. Most patients undergo
      hysterectomy because of significant pelvic abnormality. Further studies with
      longterm follow-up are needed to define the role of endometrial ablation for
      menorrhagia.

PMID- 8987922
TI  - Diagnosis and assessment of sigmoidoceles.
AB  - OBJECTIVE: This study analyzed the clinical presentation, incidence,
      characteristics as demonstrated by defecating proctography, and surgical outcomes
      of sigmoidoceles. STUDY DESIGN: Defecating proctograms were obtained on all women
      with clinical evidence of pelvic floor defects between June 1, 1991, and June 30,
      1995. The proctograms were retrospectively reviewed for the presence of a
      sigmoidocele and concomitant pelvic hernias. The distance between the maximum
      point of sigmoid descent with strain and the perineal body was measured. A chart
      review was performed to obtain clinical history, physical examination results,
      surgical treatment, and outcome. RESULTS: Nine sigmoidoceles (4.0%) were noted in
      234 defecating proctograms. The leading edge of the sigmoid hernia ranged from
      3.8 cm beyond the perineal body to 8 cm above the perineal body. All nine
      patients were found to have concomitant rectoceles by proctography, whereas only
      three were found to have enteroceles. Physical examination before proctography
      suggested that six patients had vaginal vault prolapse with enterocele, one
      patient had uterine prolapse with an enterocele, and two patients had rectoceles
      alone. Five of the seven patients clinically diagnosed with an enterocele showed
      no small bowel herniation on defecography. No sigmoidoceles were suspected by
      physical diagnosis alone. All rectoceles were diagnosed by clinical examination.
      All patients except one, who had concomitant rectal prolapse, complained of
      constipation. Two patients required manual pressure to the perineum or vagina to
      defecate. Seven of the nine patients underwent pelvic reconstructive surgery. The
      surgical procedure for sigmoidocele was determined by severity of constipation,
      degree of prolapse, and sigmoid redundancy at the time of surgery. Two patients
      underwent sigmoid resection with sigmoidopexy, one patient had sigmoidopexy
      alone, and four patients had Halban obliteration of the cul-de-sac. Two patients
      are successfully using pessaries. Follow-up from 4 months to 2 years (mean 12
      months) showed no recurrence of an apical defect by clinical examination. One
      patient had a recurrent rectocele to the hymenal ring with strain. Five patients
      had no complaints of constipation, whereas two noted improvement but continued
      symptoms. Both these patients had Halban procedures only, and one had the
      recurrent rectocele. CONCLUSIONS: Sigmoidoceles are an uncommon but not rare
      finding with apical support defects. Physical examination alone does not make the
      diagnosis. All patients had a rectocele, which substantiates a posterior vaginal
      support defect. In these patients there was a strong association with
      constipation that responded to surgical correction, but the degree of anatomic
      distortion did not always correlate with functional impairment.

PMID- 8987923
TI  - The role of colpocleisis with urethral lengthening in transsexual phalloplasty.
AB  - OBJECTIVE: Transsexual surgery is an unique area of rarely performed surgery.
      This study examines factors that have significance in the prevention of major
      morbidity in this unusual surgery. The role of the gynecologist in the
      psychologic, endocrine, and operative management is presented. STUDY DESIGN:
      Initial operations were complicated by fistulas at the urethra-to-phallus
      anastomosis site. After reviewing these complications, we modified our approach
      to include a two-stage procedure allowing for healing before microsurgery and
      sparing of the anterior vaginal wall during vaginal hysterectomy and
      colpocleisis. By sparing the anterior vaginal wall, we were able to better extend
      the urethra for later phallus attachment. RESULTS: Using the two-stage procedure
      at colpocleisis allowed a significant reduction in the fistula rate. (p = 0.0087)
      with the effective elimination-fistulas, the use of stiffeners during
      phalloplasty for better functional results is possible. CONCLUSION: Extending the
      urethra during colpocleisis allows for better healing and significantly decreased
      fistula formation. Proper blood supply for microvascular surgery and adequate
      tissue for the anastomosis site contribute to better results.

PMID- 8987924
TI  - Laparoscopic management of suspicious adnexal masses.
AB  - OBJECTIVE: Our aim was to evaluate the feasibility and applicability of operative
      laparoscopy in the management of adnexal masses that do not meet the standard
      serum CA 125 and ultrasonographic criteria for benignity. STUDY DESIGN: One
      hundred thirty-eight patients underwent operative laparoscopy for removal of
      suspicious adnexal masses. The CA 125 level was > 35 mlU/ml in 39 of 138 (28%)
      patients; ultrasonographic findings were abnormal in 127 of 138 (92%); masses
      were > 10 cm in 43 of 138 (32%) of patients. RESULTS: Malignancies were
      discovered in 14% (19/138) of patients. Eight percent (11/138) of the procedures
      were converted to laparotomy, six because of inability to dissect the mass
      laparoscopically and five for staging or debulking of carcinoma. Operative times
      ranged from 25 to 210 minutes, with a mean of 86. Three major complications were
      encountered-an enterotomy and a lacerated vena cava, both of which were repaired
      laparoscopically, and a small bowel herniation through a lateral port site that
      required reoperation. Hospital stays ranged from 0 to 11 days, with a mean of
      1.5. In two patients with "apparent" stage I adnexal carcinomas recurrence was
      diagnosed 6 and 38 months after surgery. CONCLUSIONS: Laparoscopic management of
      suspicious adnexal masses is technically feasible, with a low rate of morbidity
      and a short hospital stay. Adnexal carcinomas can be identified and managed
      appropriately with staging and complete resection as indicated.

PMID- 8987925
TI  - Use of a pedicled rectus abdominis muscle flap sling in the treatment of
      complicated stress urinary incontinence.
AB  - OBJECTIVE: A pedicled rectus muscle flap sling in the treatment of complicated
      stress urinary incontinence was evaluated. STUDY DESIGN: Thirty-two women
      underwent a combined vaginal and abdominal sling operation for stress
      incontinence with a pedicled muscle flap developed from the rectus abdominis
      muscle. All operations were performed jointly by the same two surgeons. The
      procedure involved transecting one rectus abdominis muscle just above its first
      tendinous intersection and isolating the muscle as a flap on its inferior
      vascular pedicle. The muscle flap was then swung beneath the urethra and bladder
      neck, pulled into the retropubic space on the contralateral side, and sewn to the
      obturator internus fascia or to Cooper's ligament. All patients undergoing the
      procedure had demonstrable stress incontinence on physical examination and
      underwent preoperative fluoroscopic video urodynamics. The diagnosis of
      complicated stress incontinence was based on the presence of one or more of the
      following factors: previous failed antiincontinence surgery (33 operations in 22
      patients, average 1.5 operations), open vesical neck on fluoroscopy (14
      patients), urethral closure pressure < or = 30 cm H2O by the Brown-Wickham
      technique (16 patients), or massive vaginal prolapse and demonstrable stress
      incontinence with the prolapse reduced and the urethra supported in a normal
      position (16 patients). Follow-up ranged from 2 to 13 months (average 6 months).
      Surgical outcome was assessed by physical examination and a detailed telephone
      interview conducted by a physician who was not involved in the operations.
      RESULTS: Twenty-eight patients (87.5%) were satisfied with the results of the
      operation. There were four surgical failures (12.5%). Stress incontinence
      persisted in three patients after surgery, and one patient who had mixed
      incontinence before surgery was cured of stress incontinence but continued to
      have significant urinary leakage as a result of detrusor overactivity. There
      appears to be less voiding dysfunction with this technique than with other sling
      procedures for stress incontinence. CONCLUSIONS: The sling procedure with a
      rectus abdominis muscle flap appears to be a viable surgical technique in the
      treatment of complicated stress incontinence. Further study is needed to assess
      the long-term results of this operation and to evaluate its proper place in
      reconstructive pelvic surgery.

PMID- 8987926
TI  - Interobserver and intraobserver reliability of the proposed International
      Continence Society, Society of Gynecologic Surgeons, and American Urogynecologic
      Society pelvic organ prolapse classification system.
AB  - OBJECTIVE: Our purpose was to determine the intraobserver and interobserver
      reliability of site-specific measurements and stages with the proposed
      international Continence Society, Society of Gynecologic Surgeons, and American
      Urogynecologic Society 1994 draft prolapse terminology document. STUDY DESIGN:
      Women who completed informed consent procedures underwent pelvic examinations by
      two investigators, each blinded to the results of the other's examination. The
      reproducibility of the nine site-specific measurements and the summary stage and
      substage were analyzed with Spearman's correlation coefficient (rs) and Kendel
      tau B Correlation Coefficient (tau b), respectively. Similar analyses were
      performed on supine and upright examinations performed at two different times by
      one examiner. RESULTS: Experienced examiners averaged 2.05 minutes per
      examination and new examiners averaged 3.73 minutes. In the study of
      interobserver reliability, 48, subjects, mean age 61 +/- 14 years, parity 3 +/-
      2, weight 74 +/- 31 kg, comprised the study population. Correlations for each of
      the nine measurements were substantial and highly significant (rs 0.817, 0.895,
      0.522, 0.767, 0.746, 0.747, 0.913, 0.514, and 0.488, p = 0.0008 to < 0.0001).
      Staging and substaging were highly reproducible (tau b 0.702 and 0.652). In no
      subject did the stage vary by more than one; in 69% stages were identical. In the
      study of intraobserver reliability, for 25 subjects correlations for each of the
      nine measurements were equally strong (rs 0.780, 0.934, 0.765, 0.759, 0.859,
      0.826, 0.812, 0.659, 0.431). Measurements from the upright examinations reflected
      greater prolapse. Staging and substaging were highly reproducible (tau b 0.712
      and 0.712). In no subject did the stage vary by more than one; in 64% stages were
      identical. All stage discrepancies represented an increase in the upright
      position. CONCLUSIONS: There is good reproducibility of measures with the
      proposed system. The data suggest that the reliability is independent of examiner
      experience. Patient position is likely important in maximizing the severity of
      the prolapse.

PMID- 8987927
TI  - The efficacy of Marlex mesh in the repair of severe, recurrent vaginal prolapse
      of the anterior midvaginal wall.
AB  - OBJECTIVE: The study assesses the efficacy and complications of Marlex mesh in
      repairing severe recurrent anterior vaginal wall prolapse. STUDY DESIGN: Twenty
      four patients with two or more postsurgical recurrences of severe anterior
      vaginal wall prolapse were divided into control and treatment groups.
      Transvaginal repair was similar between groups except for reinforcement of the
      anterior vaginal wall with synthetic mesh. Two examiners graded preoperative and
      postoperative support over the following 2 years (K = 0.9). Fisher's exact test,
      log-linear analysis, and analysis of variance were used to compare categoric and
      continuous variables. RESULTS: Four patients in the control group and none in the
      treatment group had recurrent anterior vaginal wall prolapse (p < 0.05). Three
      patients had mesh-related complications. CONCLUSION: Repair with a synthetic mesh
      decreased the expected incidence of severe recurrent anterior vaginal prolapse
      but was associated with common complications related to synthetic mesh. Mesh
      reinforcement is an effective treatment for severe recurrent prolapse of the
      anterior midvaginal wall.

PMID- 8987928
TI  - Incidence of recurrent cystocele after anterior colporrhaphy with and without
      concomitant transvaginal needle suspension.
AB  - OBJECTIVE: Our purpose was to compare the recurrent cystocele rate after anterior
      colporrhaphy versus anterior colporrhaphy performed in conjunction with
      transvaginal needle bladder neck suspension. STUDY DESIGN: A retrospective chart
      review of all patients undergoing anterior colporrhaphy with and without needle
      bladder neck suspension over a 3-year period was conducted. Preoperatively all
      patients had symptomatic anterior vaginal wall relaxation. Patients undergoing
      concomitant needle suspension procedures had genuine stress incontinence. Twenty
      seven patients underwent anterior colporrhaphy alone, and 40 patients underwent
      anterior colporrhaphy with needle suspension. Demographic data including age,
      parity, menopausal status, and use of estrogen replacement was collected for each
      group. The recurrence rate of anterior vaginal wall relaxation was determined for
      each group by reviewing standardized postoperative office notes. RESULTS: There
      was no significant difference in the duration of follow-up between the two groups
      (13.2 months in the anterior repair group vs 13 months in the anterior repair
      needle suspension group). However, a significant difference in recurrent
      cystocele rates was found between the two groups (7% [2/ 27] in the anterior
      repair group compared with 33% [13/40] in the anterior repair-needle suspension
      group, p < 0.01). CONCLUSION: The incidence of recurrent cystocele is
      significantly higher after anterior colporrhaphy with concomitant needle bladder
      neck suspension compared with anterior colporrhaphy alone. This difference may be
      related to the vaginal retropubic dissection at the time of transvaginal needle
      bladder neck suspension resulting in an iatrogenic paravaginal defect or
      denervation of the anterior vaginal wall.

PMID- 8987929
TI  - Guidelines to determine the route of oophorectomy with hysterectomy.
AB  - OBJECTIVES: Our purpose was to determine whether there is adequate visibility and
      access for transvaginal oophorectomy in most patients and the success rate of the
      transvaginal approach. The final goal was to establish objective guidelines for
      choosing the route of oophorectomy with hysterectomy. STUDY DESIGN: Patients
      underwent laparoscopy-assisted vaginal hysterectomy (n = 91) or vaginal
      hysterectomy (n = 875). Ovarian removal, either unilateral (n = 97) or bilateral
      (n = 187), was carried out for clinical or prophylactic reasons. The
      accessibility of the ovaries for transvaginal removal was assessed by stretching
      the infundibulopelvic ligament and grading the position of the ovaries from 0 (no
      descent) to III (descent past the hymenal ring with traction). RESULTS: In 158
      patients transvaginal bilateral oophorectomy was performed without laparoscopic
      assistance. In another 29 patients bilateral transvaginal oophorectomy was
      performed with laparoscopy-assisted vaginal hysterectomy, and prophylactic
      bilateral oophorectomy by the transvaginal route was successful in all but 1 of
      143 patients with ovaries of grade I or higher. In 20 patients laparoscopic lysis
      of adhesions was necessary to permit transvaginal oophorectomy. Ninety-seven
      patients underwent transvaginal unilateral oophorectomy, 74 with conventional
      vaginal hysterectomy and 23 with laparoscopy-assisted vaginal hysterectomy. Among
      the patients not having oophorectomy, all ovaries had sufficient mobility to have
      been removed transvaginally. CONCLUSION: Good surgical practice dictates that
      visibility and accessibility be the primary criteria for selecting the route of
      oophorectomy with hysterectomy. In most patients the ovaries are visible and
      accessible to transvaginal removal.

PMID- 8987930
TI  - Osmotic lysis of tumor spill in ovarian cancer: a murine model.
AB  - OBJECTIVE: Our purpose was to determine, in the murine model, whether human
      ovarian cancer cells injected intraperitoneally are subject to osmotic lysis by
      peritoneal lavage with sterile water, thereby decreasing the establishment of
      peritoneal implants. STUDY DESIGN: Preliminary experiments on six nude mice
      determined that the injection of 20 million cells of the SKOV-3 cell line
      reliably leads to the establishment of intraperitoneal tumor xenografts in the
      mice within 60 days. Four other nude mice functioned as sham controls undergoing
      peritoneal lavage with 3 to 4 ml of saline solution or sterile water to determine
      any adverse effects from the lavage alone. Subsequently, 36 nude (nu/nu) mice
      were injected intraperitoneally with 1 ml of the SKOV-3 cell line at a
      concentration of 20 million cells per milliliter. Alternate mice then underwent
      intraperitoneal lavage with either 3 to 4 ml of normal saline solution (control
      group) or sterile water (study group). The mice were followed up until tumor
      growth caused a moribund status or until 60 days after injection and then were
      killed. At necropsy the number and size of tumor nodules were recorded, and each
      mouse was assigned a composite tumor score. Statistical comparison used the X2 or
      Fisher's exact test for discrete variables. Time to failure analysis used the
      Kaplan-Meier method. RESULTS: Tumor growth occurred in 35 of 36 (97%) of the mice
      during the study period. In the first 30 days 89% of the saline solution group
      grew clinically visible tumor compared with 55% of the water group (p = 0.03).
      Ascites developed more frequently in the water group than in the saline solution
      group. The median tumor scores at death were significantly higher for the water
      group versus the saline solution group. Survival time, as determined by the time
      from injection until moribund status, was worse for the water group (p = 0.002).
      CONCLUSIONS: Intraperitoneal lavage with sterile water did not offer protection
      against the establishment of xenografts after the intraperitoneal injection of
      human ovarian cancer cells in the nude mouse model.

PMID- 8987931
TI  - Choroid plexus cysts and trisomy 18: risk modification based on maternal age and
      multiple-marker screening.
AB  - Choroid plexus cysts are more common in fetuses with chromosomal aneuploidies,
      particularly trisomy 18. Although it is accepted that the risk of karyotypic
      abnormality justifies amniocentesis when associated abnormalities are present,
      disagreement continues as to the risk of trisomy 18 in a fetus with an isolated
      choroid plexus cyst. We propose consideration of maternal age and multiple-marker
      screening for chromosomal aneuploidy in the assessment of risk. Bayesian
      statistical modeling was used to calculate the risk of trisomy 18 from age
      related risk figures for trisomy 18 and the incidence of isolated choroid plexus
      cysts in fetuses with trisomy 18. The risk was further modified on the basis of
      the ability of multiple-marker screening to detect fetuses with trisomy 18. From
      risk estimates calculated across maternal ages 20 to 45 years, the risk of
      trisomy 18 does not approach that of amniocentesis until a maternal age of > or =
      37 years. Therefore in the presence of an isolated choroid plexus cyst and normal
      multiple-marker screen results amniocentesis is justified only in the patient
      with advanced maternal age.

PMID- 8987932
TI  - Postmenopausal adnexal cysts: how clinical management has evolved.
AB  - It has been 25 years since the introduction of the palpable postmenopausal ovary
      syndrome. As diagnostic imaging techniques have improved, small findings imaged
      in the adnexa were often handled as if they had been palpated. Clinical
      management was not made on any scientific basis. New endovaginal probes afford a
      degree of image magnification that is as if we are doing ultrasonography through
      a low-power microscope ("sonomicroscopy"). More recent additions of CA 125
      measurement, color flow Doppler, and advanced endoscopic surgical techniques have
      come into the picture. This report attempts to describe an approach to
      postmenopausal cystic adnexal masses that synthesizes available information and
      techniques. It is designed to prevent unnecessary surgery and to prevent undue
      anxiety but not to miss or, at the least, unduly delay the diagnosis of ovarian
      cancer when it is, in fact, present.

PMID- 8987933
TI  - Human immunodeficiency virus testing and counseling: nuts and bolts.
AB  - The human immunodeficiency virus poses an increasing health hazard to women.
      Physicians must recognize this risk and evaluate their patients for human
      immunodeficiency virus. Because of general increased awareness and the
      recommendations that all prenatal patients be offered human immunodeficiency
      virus testing and counseling, more and more women will be tested, yet counseling
      has not become a routine aspect in the evaluation of patients. This article
      reviews the key components of human immunodeficiency virus testing and
      counseling, including test interpretation, risk assessment, risk reduction, and
      pretest and posttest counseling. Familiarity with these areas should enable the
      practitioner to feel comfortable in providing this service.

PMID- 8987934
TI  - Pregnancy outcome and intelligence at age five years.
AB  - OBJECTIVE: Our purpose was to determine the influence of being small for
      gestational age at term and being preterm < 34 weeks on cognitive functioning at
      age 5 years. STUDY DESIGN: Five hundred forty-six children of black low-income
      mothers, nearly all at risk for being small for gestational age, followed up
      prenatally with early ultrasonographic gestational age dating, were classified as
      either term appropriate for gestational age, term small for gestational age, or
      preterm at < 34 weeks. At a mean of 5.5 +/- 0.5 years, a Wechsler Preschool and
      Primary Scale of Intelligence-Revised intelligence quotient test was
      administered. An intelligence quotient < 70 was used to define mental
      retardation. Univariate and multivariate analyses adjusted for maternal age,
      smoking, education and language skills, home environment, and child gender and
      preschool attendance were performed. RESULTS: Term small-for-gestational-age and
      preterm infants at < 34 weeks had 4 and 6 point intelligence quotient reductions
      compared with term appropriate-for-gestational-age infants. In the regression
      analyses these differences in intelligence quotient remained significant after
      confounders were adjusted. High maternal receptive language level (8 points), a
      positive home environment (5 points), and attendance at preschool (5 points) were
      each significantly associated with an increase in intelligence quotient.
      CONCLUSION: Both term small-for-gestational-age infants and those born at < 34
      weeks had a significantly lower mean intelligence quotient, and small-for
      gestational-age infants had an increased risk of mental retardation at age 5
      years. Higher maternal language skills, a positive home environment, and
      attendance at preschool each were associated with an increase in the mean
      intelligence quotient of 5 to 7 points.

PMID- 8987935
TI  - Fetal fibronectin: a new tool for the prediction of successful induction of
      labor.
AB  - OBJECTIVE: The Bishop score is the only available tool for predicting successful
      labor induction. Vaginal fetal fibronectin has been shown to predict which
      patients will enter labor spontaneously, usually within 2 weeks. This study was
      designed to determine whether fetal fibronectin can also predict the success of
      labor induction. STUDY DESIGN: Term patients undergoing labor induction had a
      single swab from the vagina tested for fetal fibronectin before initiation of
      cervical ripening or oxytocin. The swab was tested with a blinded qualitative
      immunoassay for fetal fibronectin (positive > or = 50 ng/ml). RESULTS: Of the
      overall 160 subjects, 108 had a positive and 52 had a negative fetal fibronectin
      result. Patients with a positive result had a lower cesarean section rate (15% vs
      27%, p = 0.05) and shorter intervals to delivery, including first dose of
      prostaglandin to delivery interval (21.3 vs 35.8 hours, p = 0.0001) and first
      stage of labor (14.8 vs 21.2 hours, p = 0.0009). These differences remain similar
      even in nulliparous women with Bishop scores < or = 5, with patients with
      positive results having statistically shorter intervals to delivery and similar
      differences in cesarean section rates (22% vs 35%), although this difference was
      not significant. In this subgroup more than half the patients in the negative
      results group (11/20) were undelivered after 24 hours and were judged to require
      a second dose of prostaglandin compared with only 2 of 53 in the group with
      positive results (p = 0.000001). By stepwise logistic regression analysis the
      predictive ability of a positive result for fetal fibronectin was found to be
      independent of the Bishop score. CONCLUSIONS: Vaginal fetal fibronectin appears
      to be an efficacious new test that independently predicts which patients will
      have shorter and easier inductions of labor and lower cesarean section rates,
      even nulliparous patients with low Bishop scores. This test has the potential for
      clinical utility and cost reduction.

PMID- 8987936
TI  - Further defining the risks confronting twins.
AB  - OBJECTIVE: We report the absolute and relative risks for neonatal and infant
      death, low and very low birth weight, and delivery at < 33 and < 35 weeks'
      gestation in twin pregnancy stratified by maternal race and age, as well as
      gender pair combinations of the twins. STUDY DESIGN: Data on 324,141 twin infants
      were obtained from the 1985 to 1988 U.S. Linked Birth/ Infant, Death Data Sets.
      In this observational cohort study, we analyzed the outcomes of 138,779 twin
      pregnancies of white and black women that ended with the delivery of two live
      born infants. RESULTS: Rates for the aforementioned outcomes are increased for
      black infants, for male-male pairs compared with male-female pairs (with female
      female pairs being intermediate), and for young mothers. For male-male twins born
      to young (< or = 22 years old) black women, relative risks range from 2.1 for
      both pair members being low birth weight (< 2500 gm) to 5.0 for both pair members
      dying in infancy, when male-female pairs born to older (> or = 28 years) white
      women served as the reference group. CONCLUSIONS: Although all twin pregnancies
      are at higher risk than singletons, risk is influenced by maternal race and age,
      as well as gender pair combination. These analyses provide useful information for
      counseling women pregnant with twins. Furthermore, they suggest that failure to
      consider variations in baseline risk may have seriously flawed studies evaluating
      prophylactic interventions in twin pregnancy.

PMID- 8987937
TI  - Determination of chorionicity in twin gestations by high-frequency abdominal
      ultrasonography: counting the layers of the dividing membrane.
AB  - OBJECTIVE: Our aim was to determine whether chorionicity in twin gestations can
      be diagnosed by use of high-frequency ultrasonography to count the layers of
      intraamniotic membrane. STUDY DESIGN: This prospective study of 66 twin
      pregnancies between 13 and 38 weeks' gestation used transabdominal
      ultrasonography at 10 MHz. The pregnancy was classified as monochorionic when two
      layers were counted and as dichorionic when three or four layers were counted.
      The findings of the examiner, who had no other information about chorionicity,
      were compared with those of the histopathologic examination of the placenta.
      RESULTS: Ultrasonography allowed chorionicity to be determined correctly in 60 of
      63 cases (95%; 100% in the second trimester and 92% in the third. The predictive
      value for dichorionicity was 100% (48/48) and the sensitivity 94% (48/51). The 12
      monochorionic diamniotic pregnancies in which the membrane was visualized were
      all correctly diagnosed. In a thirteenth case, with severe oligohydramnios, the
      membrane could not be seen. Two patients were lost to follow-up. In 95% of the
      cases (63/66) only one examination was required to diagnose chorionicity.
      Intraobserver variability was 0% (0/26). Interobserver variability, tested by
      photographs, was 3% (2/65). CONCLUSIONS: This technique should be the first-line
      method for determining chorionicity in the second and third trimesters because it
      is the most effective. Its excellent reproducibility may be attributable to the
      use of high-frequency ultrasonography.

PMID- 8987938
TI  - Intrauterine growth restriction with absent end-diastolic flow velocity in the
      umbilical artery is associated with maldevelopment of the placental terminal
      villous tree.
AB  - OBJECTIVE: Our purpose was to evaluate the structure of placental terminal villi
      and their capillaries in pregnancies complicated by intrauterine growth
      restriction with absent end-diastolic flow velocity in the umbilical artery.
      STUDY DESIGN: Glutaraldehyde-perfusion-fixed villous tissue and a plastic cast of
      the vessels in at least two cotyledons were prepared from 10 cases with
      intrauterine growth restriction and 9 gestational age-matched control placentas.
      The structure and dimensions of 20 terminal capillary loops per cast were
      determined by scanning electron microscopic examination, and their appearances
      were correlated with the peripheral villi of the perfusion-fixed villous tissue.
      RESULTS: Capillary loops in the growth-restricted cases were sparse in number and
      significantly longer than in the control cases (218 microns [72] vs 137 microns
      [30], mean and SD, p < 0.05). They exhibited fewer branches (4.0 [1.9] per loop
      vs 6.1 [2.2], p < 0.05) and a majority of loops were uncoiled (79% vs 18%, p <
      0.05). The villous tissues from the growth-restricted cases demonstrated
      elongated villi, consistent with the cast findings. The trophoblast surface was
      wrinkled and in some areas covered by fibrin plaques. CONCLUSIONS: The terminal
      villous compartment of the placenta appears to be maldeveloped in preterm
      intrauterine growth restriction pregnancies where absent end-diastolic flow
      velocity is demonstrated in the umbilical artery before delivery. These findings
      are consistent with an increase in fetoplacental vascular impedance at the
      capillary level and may account for the impaired gas and nutrient transfer in
      this disorder.

PMID- 8987939
TI  - Novel appearance of placental nuclear monoamine oxidase: biochemical and
      histochemical evidence for hyperserotonomic state in preeclampsia-eclampsia.
AB  - OBJECTIVE: The aim of this study was to explore the relevance of placental
      monoamine oxidase at the subcellular level in the etiology of the
      hyperserotonomic state in preeclampsia-eclampsia. STUDY DESIGN: The study was
      conducted on placentas from 20 normal pregnant women and 25 women with varied
      severity of preeclampsia-eclampsia. Placental serotonin and subcellular monoamine
      oxidase activity were determined. Histochemical localization of monoamine oxidase
      was done in placental sections and cell isolates. RESULTS: Placental serotonin
      increases with severity (rsystolic 0.84, rdiastolic 0.83) and monoamine oxidase
      decreases (rsystolic 0.86, rdiastolic 0.79). Placental monoamine oxidase showed
      marked changes in preeclampsia-eclampsia. Histochemical localization of monoamine
      oxidase showed diffused low activity evenly throughout the cytoplasm and nucleus
      of the syncytiotrophoblastic cells in preeclampsia-eclampsia; in contrast, normal
      placenta showed high activity in the cytoplasm without any activity in the
      nucleus of syncytiotrophoblastic cells. Detection of monoamine oxidase activity
      in nuclei of the placenta in preeclampsia-eclampsia is a novel finding. Monoamine
      oxidase activity at the subcellular level further strengthens this observation. A
      severity-dependent decrease was present in the nuclei of placentas with
      preeclampsia-eclampsia. The use of specific substrates and inhibitors revealed
      the presence of monoamine oxidase in mitochondria and nucleus. CONCLUSION: The
      study delineates an impaired catabolism of placental serotonin in preeclampsia
      eclampsia. The novel appearance of monoamine oxidase in nuclei in proximity to
      its normal site and low activity resulting in a hyperserotonomic state may lead
      to preeclampsia-eclampsia.

PMID- 8987940
TI  - Decreased very-low-density lipoprotein and low-density lipoprotein receptor
      messenger ribonucleic acid expression in placentas from preeclamptic pregnancies.
AB  - OBJECTIVE: Our purpose was to investigate the levels of very-low-density
      lipoprotein and low-density lipoprotein receptor messenger ribonucleic acid
      expression in placentas obtained from normal pregnant women at various
      gestational stages and from patients with preeclampsia. STUDY DESIGN: The
      relative level of expression of very-low-density lipoprotein and low-density
      lipoprotein receptor messenger ribonucleic acid in each sample was determined by
      Northern blot analysis as a ratio of the intensity to that of glyceraldehyde-3
      phosphate dehydrogenase messenger ribonucleic acid. RESULTS: The expression of
      very-low-density lipoprotein receptor messenger ribonucleic acid increased
      significantly (p < 0.05) from both the first (n = 9) and second (n = 8)
      trimesters to the third (n = 11) trimester. Similarly, the expression of low
      density lipoprotein receptor messenger ribonucleic acid increased significantly
      (p < 0.05) from the first to the third trimester. The expression of both very-low
      density lipoprotein and low-density lipoprotein receptor messenger ribonucleic
      acids in third-trimester placentas from preeclamptic pregnancies (n = 13) was
      significantly lower than that in normal pregnancies in the third trimester.
      CONCLUSION: These results demonstrate the expression of very-low-density
      lipoprotein and low-density lipoprotein receptor messenger ribonucleic acids in
      the human placenta, both of which increase at late gestational stages, and the
      decreased expression in cases of preeclampsia. Abnormal fetomaternal lipid
      metabolism resulting from low expression of these receptors in the placenta may
      be involved in the pathogenesis of preeclampsia.

PMID- 8987941
TI  - Technetium Tc 99m rapidly crosses the ovine placenta and intramembranous pathway.
AB  - OBJECTIVE: This study examined the movement of the soluble ion technetium Tc 99m
      across the ovine placenta and intramembranous pathway. STUDY DESIGN: Nineteen
      fetal sheep at 131 +/- 1 (SE) days' gestation were studied. After a 1-hour
      control period technetium Tc 99m was injected into either a fetal vein (n = 7),
      the amniotic cavity (n = 5), or a maternal vein (n = 5). Maternal and fetal
      blood, fetal urine, and amniotic and allantoic fluid were sampled during the
      control period and for 8 hours after the injection. Fetal urine was drained
      externally throughout the experiment. In five animals technetium Tc 99m was
      injected intraamniotically after the fetus was killed with air emboli and sampled
      as described. RESULTS: Intrafetally injected technetium Tc 99m rapidly crossed
      the placenta; then it entered and was concentrated in the amniotic cavity.
      Intraamniotically injected technetium Tc 99m rapidly entered into the fetal
      circulation. The maternally injected technetium Tc 99m rapidly crossed the
      placenta into the fetus, suggesting a half-time for placental exchange of < 50
      minutes. The technetium Tc 99m injected into the dead fetus group demonstrated
      significantly less maternal absorption than in the live fetus group. CONCLUSIONS:
      The soluble ion technetium Tc 99m demonstrated a much more rapid movement in both
      directions across the ovine placenta then previously demonstrated for the smaller
      ion sodium. Technetium Tc 99m rapidly crossed the intramembranous pathway
      bidirectionally, suggesting a high permeability of the intramembranous pathway.
      Minimal maternal absorption of technetium Tc 99m in the dead fetus group suggests
      little transmembranous absorption by the mother.

PMID- 8987942
TI  - Ultrasonographically adjusted midtrimester risk of trisomy 21 and significant
      chromosomal defects in advanced maternal age.
AB  - OBJECTIVE: Our purpose was to determine whether normal midtrimester
      ultrasonography results reduces the risk of fetal Down syndrome and any
      clinically significant chromosomal defects in pregnancies with advanced maternal
      age and to develop risk tables on the basis of age and ultrasonographic results.
      STUDY DESIGN: Biometry data were obtained in 4079 women between 15 and 24 weeks
      undergoing amniocentesis for maternal age. Expected values of humerus, femur,
      both combined, and abdominal circumference based on biparietal diameter were
      generated from a normal group. Observed/expected values of each parameter and
      nuchal thickness > or = 6 mm was used to screen for Down syndrome and any
      clinically significant chromosome defects. Receiver-operator characteristic
      curves were used to determine threshold screening values for each parameter. By
      use of stepwise logistic regression the optimal measurements for detection of
      chromosome anomalies were established. An abnormal ultrasonography result was
      defined as either abnormal biometry choroid plexus cysts or a structural defect.
      RESULTS: The finding of shortened humerus (observed/expected < 0.90), abnormal
      nuchal thickness, or an anatomic defect had the highest sensitivity for Down
      syndrome detection, 70.6%, p < 0.0001, whereas a short humerus, small abdominal
      circumference, (observed/expected < 0.92), or an anatomic defect had a
      sensitivity of 46.7%, p < 0.0001, for any significant chromosome defect. With a
      normal ultrasonography the risk of Down syndrome in a 39-year-old woman falls
      from 1:100 to < 1:292. CONCLUSION: A normal ultrasonography substantially reduces
      the risk of Down syndrome and any chromosome abnormality. This information is
      useful in counseling women who decline amniocentesis on the basis of maternal
      age.

PMID- 8987943
TI  - Fetal brain sparing is associated with accelerated shortening of visual evoked
      potential latencies during early infancy.
AB  - OBJECTIVE: Our purpose was to assess the effects that fetal growth restriction
      exerts on the myelination of the developing brain. STUDY DESIGN: Fetal
      haemodynamic centralization, an adaptive strategy to growth restriction caused by
      placental insufficiency, was determined by Doppler ultrasonography. Infants with
      a raised ratio between umbilical artery pulsatility index and cerebral artery
      pulsatility index are severely growth restricted. Visual evoked potentials give
      information on the degree of brain myelination. Shortening of visual evoked
      potential latencies is a normal feature of myelination. In a consecutive series
      of 105 Neonates, visual evoked potentials were recorded at the corrected ages of
      6 months and 1 years. Correction for possible confounders, such as cranial
      ultrasonographic findings, gestational age, and head circumference, was
      performed. RESULTS: At 6 months, infants with a raised umbilical artery/cerebral
      artery pulsatility index ratio have shorter visual evoked potential latencies.
      Opposite of neonates with a normal umbilical artery/cerebral artery ratio, they
      show no postnatal maturational shortening of visual evoked potential latencies.
      CONCLUSION: Accelerated neurophysiologic maturation, found in infants with a high
      umbilical artery/cerebral artery ratio, might be the result of a beneficial
      adaptive process to severe fetal growth restriction.

PMID- 8987944
TI  - Three classes of radical vaginal hysterectomy for treatment of endometrial and
      cervical cancer.
AB  - OBJECTIVES: The aims of this study were to (1) describe three types of extended
      vaginal hysterectomy with different degree of radicality, (2) to identify
      possible indications for each one of them, and (3) to encourage individualization
      of the treatment, with special reference to the reevaluation of the role of
      vaginal surgery in gynecologic oncology. STUDY DESIGN: The surgical-anatomic
      principles of radical vaginal surgery and the techniques of three increasingly
      extended vaginal hysterectomies are illustrated. Possible indications are pointed
      out on the basis of our personal experience from previously published
      retrospective studies. RESULTS: Class I extended vaginal hysterectomy allows the
      "en bloc" dissection of the uterus along with the upper third of vagina and both
      the adnexa. The parametria are not removed. This procedure has proved to be of
      value for treatment of stage I endometrial cancer. In the class II extended
      vaginal hysterectomy the distal tract of the anterior and posterior parametria
      are preserved, whereas the cardinal ligament is entirely removed. This operation
      has shown promising results for treatment of stage IB-IIA cervical cancer of
      small volume while reducing the incidence of bladder and rectal dysfunctions. The
      class III procedure includes the complete removal of the parametria (anterior,
      lateral, and posterior). This operation has been shown to provide a high rate of
      cure for stage IB-IIA cervical cancer. CONCLUSIONS: In view of the several
      advantages of vaginal surgery, this approach should be considered in the
      individualized treatment of selected cases of endometrial and cervical cancers.
      The three classes of radical vaginal hysterectomy allow tailoring the type of
      vaginal operation to the clinical and physical characteristics of the patients.
      The combined use of extraperitoneal or laparoscopic lymphadenectomy would
      considerably extend the indications for radical vaginal operations.

PMID- 8987945
TI  - Generation of tumor-specific cytolytic T lymphocytes from peripheral blood of
      cervical cancer patients by in vitro stimulation with a synthetic human
      papillomavirus type 16 E7 epitope.
AB  - OBJECTIVE: Approximately 90% of squamous carcinomas of the cervix harbor the
      human papillomavirus and type 16 has been detected in nearly 50% of cases. Recent
      studies in mice have shown that the human papillomavirus type 16 E7 oncoprotein
      contains peptide epitopes that are processed and presented in association with a
      major histocompatibility antigen for recognition by cytolytic T lymphocytes. We
      investigated whether an epitope from human papillomavirus type 16 E7 could be
      used to generate specific human cytolytic T lymphocytes in patients with cervical
      carcinoma. STUDY DESIGN: After radiation therapy, three patients with antigen HLA
      A2 and with locally advanced cervical cancer underwent leukapheresis. Epitope
      specific cytolytic T lymphocytes were generated from the peripheral blood
      mononuclear cells by in vitro stimulation with autologous peripheral blood
      mononuclear cells pulsed with a human papillomavirus type 16 E7, HLA-A2
      restricted, synthetic peptide, E7(11-20) (YMLDLQPETT). RESULTS: In two patients
      cytolytic T lymphocytes were capable of E7(11-20)-specific, HLA-A2-restricted
      cytolysis of the peptide-pulsed, HLA-matched, T2 target cell line. Cytolytic T
      lymphocytes from one of these patients also demonstrated specific cytolysis
      against the HLA-A2+, HPV-16+ CaSki cervical cancer cell line but did not lyse
      either HLA-A2+, HPV-16- MS-751 cells or HLA-A2-, HPV-16- HT-3 cells. CONCLUSIONS:
      These experiments demonstrate that novel cytolytic T lymphocytes that recognize a
      human papillomavirus type 16 E7 epitope can be generated by using the peripheral
      blood mononuclear cells from irradiated patients with cervical cancer. In
      addition, because CaSki cells were specifically lysed by the cytolytic T
      lymphocytes, these data indicate that the peptide E7(11-20) is endogenously
      processed and presented on the cell surface of the CaSki cells. The demonstration
      of epitope-specific lysis of cytolytic T lymphocytes of HPV-16+ cervical cancer
      cells supports further efforts to develop human papillomavirus peptide-based
      vaccines or antigen-specific adoptive immunotherapy for the prevention and
      treatment of cervical carcinoma.

PMID- 8987946
TI  - Relative influence of age and menopause on total and regional body composition
      changes in postmenopausal women.
AB  - OBJECTIVE: We measured total and regional body composition to evaluate the
      differences in body composition associated with menopause and to determine
      whether the changes in fat distribution were more related to age or to menopause.
      STUDY DESIGN: Two hundred five healthy white women who had never received
      estrogen replacement therapy were studied according to menopausal status and age.
      Bone mass and body composition were measured by dual x-ray absorptiometry. The
      proportions of android and gynoid fat were calculated in all women and
      differences were sought by statistical analysis. RESULTS: Compared with
      premenopausal women, postmenopausal women were characterized by a significant
      increase in the proportion of android fat and the ratio trunk fat/leg fat,
      whereas the absolute amount of body fat mass did not significantly change. The
      different variables of android fat distribution tended to correlate better with
      years since menopause than with age. In multiple linear regression, years since
      menopause was a predictor of body fat mass and fat trunk, whereas age was not a
      predictor of any of the fat distribution variables. CONCLUSIONS: This study
      underlines the early changes in body fat distribution with a shift of body fat
      toward a more central location in postmenopausal women. This change in fat
      distribution appears to be more related to menopause than to age and might,
      together with other factors, contribute to explain the increased cardiovascular
      risk reported in postmenopausal women.

PMID- 8987947
TI  - Specific immune response against Gardnerella vaginalis hemolysin in patients with
      bacterial vaginosis.
AB  - OBJECTIVE: Our goal was to study the mucosal host response in bacterial vaginosis
      by evaluating the presence of a specific immune response elicited against the
      Gardnerella vaginalis hemolysin in vaginal fluids of patients and by verifying
      its correlation with usual criteria adopted to diagnose bacterial vaginosis.
      STUDY DESIGN: A total of 123 white women attending the gynecologic care unit for
      urogenital complaints or for screening of uterine malignancies (Papanicolaou
      test) aged from 20 to 60 years, nonmenstruating, were enrolled. Bacterial
      vaginosis was diagnosed by clinical criteria and a Gram stain score > 6. RESULTS:
      We performed the determination of the antibody response in vaginal fluid against
      the hemolysin produced by G. vaginalis, a common agent present in bacterial
      vaginosis. The purified G. vaginalis toxin was a suitable antigen for detecting
      the presence of an immune response in the vaginal fluids of patients with
      bacterial vaginosis regardless of the strain of G. vaginalis present. A specific
      immunoglobulin A response was detected in 60% of women with overt bacterial
      vaginosis (Gram stain score > 6) and in 18.5% of women with intermediate vaginal
      flora (Gram stain score 4 to 6). The specificity of the test was 91%.
      CONCLUSIONS: We found a correlation between the specific local immune response to
      G. vaginalis toxin and bacterial vaginosis. The highly purified form of the toxin
      is able to discriminate disorders from the opportunistic colonization by G.
      vaginalis.

PMID- 8987948
TI  - Prognostic role of immunosuppressive acidic protein in advanced ovarian cancer.
AB  - OBJECTIVE: Our purpose was to investigate immunosuppressive acidic protein in the
      prognostic characterization of advanced ovarian cancer. STUDY DESIGN: Serum
      levels of immunosuppressive protein were prospectively measured in 80 patients
      with untreated ovarian carcinoma. To evaluate the prognostic significance of
      immunosuppressive acidic protein levels, cutoff points were studied every 50
      micrograms/ml between 450 and 1350 micrograms/ml. RESULTS: Pretreatment
      immunosuppressive acidic protein levels were not significantly associated with
      stage, histotype, grade of differentiation, postoperative residual tumor, and
      response to chemotherapy. The most significant association with survival was
      observed at a cutoff value of 1100 micrograms/ml (p = 0.0089). In the univariate
      analysis for overall survival, International Federation of Gynecology and
      Obstetrics stage and immunosuppressive acidic protein status were found to have a
      role in predicting ovarian cancer prognosis. In the multivariate analysis only
      immunosuppressive acidic protein status was significantly associated with
      survival. A statistical correlation was found between serum levels and overall
      survival (p = 0.0104, chi 2 6.56), including immunosuppressive acidic protein as
      a continuous variable. CONCLUSION: Our data suggest that immunosuppressive acidic
      protein assay is a potentially useful tool in the prognostic characterization of
      advanced ovarian cancer.

PMID- 8987949
TI  - Modulation of leukemia inhibitory factor gene expression and protein biosynthesis
      in the human fallopian tube.
AB  - OBJECTIVE: The fallopian tube is the site of fertilization and early embryonic
      growth and a common site of ectopic implantation. Although the factors
      responsible for early embryogenesis and implantation are incompletely understood,
      leukemia inhibitory factor may have an important role in early embryonic
      development and implantation. We set out to evaluate the production and
      modulation of leukemia inhibitory factor in the fallopian tube. STUDY DESIGN: We
      first investigated leukemia inhibitory factor messenger ribonucleic acid levels
      in fallopian tubes. We then investigated leukemia inhibitory factor messenger
      ribonucleic acid and protein production in tubal epithelial and stromal cell
      cultures. RESULTS: Leukemia inhibitory factor messenger ribonucleic acid is
      expressed in the fallopian tube with only slight variation during the menstrual
      cycle; however, it is markedly elevated in association with ectopic pregnancy.
      The level is higher in the tubal mucosa than in the remaining layers and is
      higher in the more distal segments of the fallopian tube. Estradiol and
      progesterone did not modulate leukemia inhibitory factor expression in epithelial
      or stromal cell cultures. Interleukin-1 alpha, tumor necrosis factor-alpha, and
      transforming growth factor-beta enhanced leukemia inhibitory factor expression in
      epithelial and stromal cells, with transforming growth factor-beta 1 enhancing
      expression by fourfold in stromal cells. Epithelial cells secreted high levels of
      leukemia inhibitory factor compared with stromal cells (332 +/- 89 vs 25 +/- 42
      pg/mg total protein). Yet stromal cells treated with transforming growth factor
      beta alone or in combination with epidermal growth factor and platelet-derived
      growth factor, as well as TNF-alpha alone or in combination with interleukin-1
      alpha enhanced secretion of leukemia inhibitory factor at or above the levels
      found with epithelial cells. CONCLUSIONS: We speculate that the high constitutive
      levels of leukemia inhibitory factor expressed in the ampullary portion of the
      fallopian tube may play a role in early embryonic development. Additionally,
      elevated expression with ectopic implantation and the marked induction of
      secretion in the tubal stroma by growth factors and cytokines suggest a link
      between inflammation, leukemia inhibitory factor, and tubal ectopic pregnancies.

PMID- 8987950
TI  - Increased monocyte chemotactic protein-1 level and activity in the peripheral
      blood of women with endometriosis. Le Groupe d'Investigation en Gynecologie.
AB  - OBJECTIVE: Our purpose was to evaluate monocyte chemotactic protein-1 in the
      peripheral blood of women with and without endometriosis. STUDY DESIGN: Fifty
      seven patients with endometriosis at laparoscopy done for infertility and pelvic
      pain were compared with 44 fertile women with no evidence of endometriosis at
      tubal ligation by laparoscopy. Monocyte chemotactic protein-1 concentration in
      the plasma was determined by enzyme-linked immunosorbent assay and its biologic
      activity was evaluated by measuring monocyte chemotaxis with use of a human
      histiocytic cell line (U937). RESULTS: Monocyte chemotactic protein-1
      concentrations (median and range of values) found in the plasma were higher in
      patients with endometriosis (163, 0 to 788 pg/ml) than in normal controls (0, 0
      to 355 pg/ml). This elevation was significant only in the minimal stage of
      endometriosis (revised American Fertility Society stage I). However, increased
      chemotactic activity (mean number of migrating cells/mm2 +/- SEM) was found in
      the stages I (1240 +/- 141), II (519 +/- 30), and III-IV (523 +/- 23) of the
      disease compared with normal controls (205 +/- 20). A total of 35% to 44% of this
      activity was inhibited in the presence of an antibody specific to monocyte
      chemotactic protein-1. CONCLUSION: Endometriosis is associated with increased
      level and activity of monocyte chemotactic protein-1 in the peripheral blood. The
      elevation and activation of this cytokine could play a relevant role in the
      immunoinflammatory process associated with the disease.

PMID- 8987951
TI  - In vitro susceptibility of clinical yeast isolates to fluconazole and
      terconazole.
AB  - OBJECTIVE: Fifty clinical yeast isolates, representing equally Candida albicans,
      Candida krusei, Candida parapsilosis, Candida tropicalis, and Torulopsis
      glabrata, were tested in vitro for their susceptibility to terconazole and
      fluconazole. STUDY DESIGN: The minimal inhibitory concentrations of terconazole
      and fluconazole were determined by use of a proposed standardized broth
      macrodilution assay. Also, the response of selected yeast isolates to 25
      micrograms of either drug was measured by agarose disk diffusion experiments.
      RESULTS: For all species the minimum inhibitory concentrations for terconazole
      were significantly lower than those for fluconazole (p < 0.05). In fact, for each
      individual isolate the minimum inhibitory concentration of terconazole was
      consistently lower than that of fluconazole. Differences in the geometric mean of
      terconazole and fluconazole minimum inhibitory concentrations were largest among
      C. krusei and T. glabrata, followed by C. parapsilosis, C. tropicalis, and C.
      albicans, in order of decreasing difference. Disk diffusion experiments suggested
      that terconazole is a more effective fungistatic agent than fluconazole is.
      CONCLUSION: Terconazole may be more effective than fluconazole against yeast
      species other than C. albicans.

PMID- 8987952
TI  - The management of placenta percreta: conservative and operative strategies.
AB  - OBJECTIVE: Our purpose was to assess preferences for the management of placenta
      percreta and identify aspects of care related to an improved outcome. STUDY
      DESIGN: Both an analysis of a questionnaire issued to members of the Society of
      Perinatal Obstetricians and a retrospective study at our institution were used to
      obtain case histories of women with placenta percreta during a recent 3-year
      period. RESULTS: Fifty-five of the 109 cases (50%) reported by members of the
      Society of Perinatal Obstetricians were suspected ante partum. Complications
      associated with this disorder included uterine rupture (3 cases), transfusion of
      > 10 units (44 cases, 40%), ureteral ligation or fistula formation (5 cases each,
      5%), infection (31 cases, 28%), perinatal death (10 cases, 9%), and maternal
      death (8 cases, 7%). Management options included surgical removal of the uterus
      and involved tissues (101 cases, 93%) and conservative treatment with the
      placenta left in situ after delivery (8 cases, 7%). More members of the Society
      of Perinatal Obstetricians responding to our survey opted for conservative
      management if adjacent tissues were involved (69% with extension into the bladder
      or gastrointestinal tract) compared with 31% when the percreta was confined to
      the uterus, p < 0.001. Conservative therapy was also associated with less blood
      loss in reported cases (median units red blood cells transfused, 0 vs 7, p =
      0.003). Two of the three cases of placenta percreta at our institution were
      identified ante partum. The third case represents the first reported with
      antepartum identification of percreta followed by deliberate conservative
      treatment. CONCLUSIONS: With greater involvement of surrounding tissues,
      conservative treatment was preferred in hemodynamically stable patients. If
      surgical excision of the placenta is attempted or necessary, physicians
      experienced in pelvic dissection must be involved because of the frequency of
      maternal morbidity and mortality.

PMID- 8987953
TI  - Determining the clinical efficacy and cost savings of successful external
      cephalic version.
AB  - OBJECTIVE: The aim of this study was to determine predictors of successful
      external cephalic version and to calculate the associated cost savings achieved
      with success. STUDY DESIGN: A retrospective study of 203 women with singleton
      gestations who underwent external cephalic version was performed. Descriptive,
      univariate, and multivariate analyses were performed on patient-specific risk
      data to predict successful version. National claims data were used for the cost
      simulation. RESULTS: Higher parity (p = 0.02), transverse-oblique presentation (p
      = 0.001), posterior placenta (p = 0.001), and a longer duration of pregnancy (p =
      0.001) significantly increased the likelihood of a successful version. Heavier
      maternal weight was negatively associated with successful version (p = 0.05). The
      cost simulation revealed an average savings of $2462 for each successful version.
      CONCLUSION: This study identifies clinical variables associated with an increased
      external cephalic version success rate. If, in fact, successful external cephalic
      version reduces both maternal and fetal morbidity associated with cesarean
      delivery and, as demonstrated in this analysis, the costs associated with the
      delivery, then greater effort should be made to maximize the success rate of
      external cephalic version.

PMID- 8987954
TI  - Prospective assessment of pregnancy outcomes after first-trimester exposure to
      fluconazole.
AB  - OBJECTIVE: Our purpose was to study prospectively the pregnancy outcome after
      first-trimester exposure to fluconazole, an effective antifungal agent
      teratogenic in animals. STUDY DESIGN: We conducted a prospective cohort study of
      women who contacted three Italian teratogen information services. We compared the
      pregnancy outcomes of 226 women exposed to fluconazole with that of 452 women
      exposed to nonteratogenic agents, with use of logistic regression to control for
      potential confounders. RESULTS: Among the 226 pregnancies exposed to fluconazole
      there were 22 miscarriages, 1 stillbirth, and 7 infants with congenital
      anomalies. The prevalence of these outcomes and of neonatal growth parameters and
      the rate of neonatal complications were similar to those in the reference group.
      Women in the fluconazole group had a fivefold increased occurrence of induced
      abortions. CONCLUSIONS: First-trimester exposure to fluconazole does not appear
      to increase the prevalence of miscarriages, congenital anomalies, and low birth
      weight.

PMID- 8987955
TI  - Cocaine and beta-adrenergic receptor function in pregnant myometrium.
AB  - OBJECTIVE: Our purpose was to evaluate the in vitro effect of cocaine on beta
      adrenergic receptor function in pregnant human myometrium. STUDY DESIGN:
      Myometrium was obtained from 25 pregnant women at term who were undergoing
      cesarean section but who were not in labor. Membrane preparations were assayed
      for cyclic adenosine monophosphate production after exposure to isoproterenol,
      sodium fluoride, or forskolin in the presence and absence of either cocaine or
      benzoylecgonine, a major metabolite of cocaine. RESULTS: Cocaine inhibited
      isoproterenol-induced cyclic adenosine monophosphate production in concentrations
      as low as 10(-8) mol/L but had no effect on cyclic adenosine monophosphate
      production induced by sodium fluoride or forskolin. Benzoylecgonine (10(-4)
      mol/L) had no effect on isoproterenol-induced cyclic adenosine monophosphate
      production. CONCLUSION: Cocaine is a beta-adrenergic receptor antagonist in human
      myometrium at concentrations as low as 10(-8) mol/L. This acute effect of cocaine
      may result in increased uterine contractility with adrenergic stimulation,
      potentially leading to increased uterine activity associated with acute cocaine
      use.

PMID- 8987957
TI  - Nitric oxide synthase activity in the gravid rat uterus decreases a day before
      the onset of parturition.
AB  - OBJECTIVE: Our purpose was to determine the timing, tissue location, and isoform
      of the uterine nitric oxide synthase activity decrease at term in gravid rat
      uteri. STUDY DESIGN: Nitric oxide synthase specific activity was assayed in rat
      uteri 11 through 22 days' gestation by the difference in radiolabeled arginine to
      citrulline conversion with and without the cofactor reduced nicotinamide adenine
      dinucleotide phosphate. Nitric oxide synthase isoform was assessed by calcium
      sensitivity and subcellular location. RESULTS: Rat uterine nitric oxide synthase
      activity decreased between days 15 and 21 of gestation but did not decrease
      further at term (day 22), before and after the onset of labor. Decidual nitric
      oxide synthase activity exceeded the myometrial activity at 15 days' gestation,
      but then the two were equal at 18 through 22 days' gestation. The nitric oxide
      synthase activity was calcium insensitive except for half the decidual cytosolic
      activity on day 15. CONCLUSION: The decrease in pregnant rat uterine nitric oxide
      synthase activity coincides with the preparation of the uterus for parturition
      rather than the final activation of labor.

PMID- 8987956
TI  - Oxytocin receptors in bovine cervix during pregnancy and parturition: gene
      expression and cellular localization.
AB  - OBJECTIVES: Our purpose was to determine the expression of transcripts encoding
      the oxytocin receptor protein in bovine cervix during pregnancy and parturition,
      the cellular localization of immunoreactive oxytocin receptors, and oxytocin
      receptors concentrations in the same tissues. STUDY DESIGN: Ribonuclease
      protection assay for oxytocin receptor messenger ribonucleic acid was used to
      determine gene expression in bovine cervical tissues obtained from 20 cows
      throughout pregnancy and parturition, cellular localization of oxytocin receptors
      was determined by immunohistochemistry, and tritiated oxytocin binding was
      measured in each tissue. RESULTS: Oxytocin receptor gene expression and tritiated
      oxytocin binding were well correlated in each instance. During pregnancy the
      level of oxytocin receptor messenger ribonucleic acid was very low; it was
      increased at term with a further, marked increase at parturition. Tritiated
      oxytocin binding also increased dramatically at parturition and was most abundant
      in the mucosal layer. Strong oxytocin receptor immunoreactivity was present in
      mucosal epithelial cells, and scattered muscle cells in the muscular part showed
      the signal. CONCLUSIONS: Our results, together with the previous finding that
      oxytocin stimulates prostaglandin E2 release from cervical tissue in vitro,
      indicate that cervical mucosal epithelial cells are targets for oxytocin at
      parturition and may mediate release of prostaglandin E2.

PMID- 8987958
TI  - Bradykinin-mediated relaxation of isolated maternal resistance arteries in normal
      pregnancy and preeclampsia.
AB  - OBJECTIVE: The aim of the study was to investigate bradykinin-mediated
      vasodilator function in small arteries from normotensive pregnant and nonpregnant
      women and from women with preeclampsia. STUDY DESIGN: Small subcutaneous arteries
      (approximately 250 microns luminal diameter) were dissected from biopsy specimens
      obtained at cesarean section from 24 normotensive pregnant women and 6 women with
      preeclampsia and during abdominal surgery in 15 nonpregnant women. Vascular
      function was assessed after arteries were mounted on a small vessel myograph.
      RESULTS: Preconstricted arteries from normotensive pregnant women demonstrated
      enhanced relaxation to bradykinin compared with those from nonpregnant women (p <
      0.05), whereas arteries from women with preeclampsia showed blunted responses
      compared with those from normotensive pregnant women (P < 0.01). Relaxation in
      all groups was attenuated in the presence of the nitric oxide synthase inhibitor
      N omega-nitro-L-arginine so that it became similar in the three groups.
      Indomethacin had a small but significant inhibitory effect on bradykinin-induced
      relaxation, but this component of relaxation was no different among groups.
      Sensitivity of arteries to norepinephrine and sodium nitroprusside showed no
      significant differences in the three groups of women. CONCLUSION: This study
      provides evidence for an increase in bradykinin-mediated nitric oxide synthesis
      from the vascular endothelium of small arteries from the peripheral circulation
      of normotensive pregnant women and a relative reduction in women with
      preeclampsia. In turn, these changes may contribute to vasodilation in normal
      pregnancy and elevation of the blood pressure in preeclampsia.

PMID- 8987959
TI  - Ectopic pregnancy.

PMID- 8987960
TI  - Less vaginal cuff and pelvic infection after laparoscopic hysterectomy?

PMID- 8987961
TI  - Minilaparotomy: a laparoscopic viewpoint.

PMID- 8987962
TI  - Gestational thrombocytopenia: is it new?

PMID- 8987963
TI  - Doppler velocimetry of hepatic blood flow in postpartum patients with HELLP
      syndrome (hemolysis, elevated liver enzymes, and low platelets)

PMID- 8987964
TI  - The independent medical examination: cardiology assessment.
AB  - Insurance companies frequently seek medical opinions from various specialists
      concerning the severity of a medical problem, the appropriateness of a treatment
      plan and a assessment of the degree of medical impairment in persons who claim
      they are entitled to disability benefits. The insurer is requesting a medical
      opinion from a physician not involved in the care of the claimant and with no
      regular business ties to the insurance company; the insurance industry refers to
      this as an independent medical examination (IME). The purpose of the cardiology
      IME is to have an objective assessment concerning symptomatology and disease
      severity, and to reach a conclusion as to whether the cardiology problem is
      expected to prevent a return to work. The cardiologist needs to narrow the focus
      on the heart solely in terms of its primary function, that is, its ability to
      pump blood.

PMID- 8987965
TI  - Serum ferritin and heart disease: the effect of moderate exercise on stored iron
      levels in postmenopausal women.
AB  - OBJECTIVE: To determine the effect of a moderate exercise regimen on stored iron
      as measured by serum ferritin in previously sedentary postmenopausal women.
      DESIGN: Randomized assignment to one of three groups: a five day/week walking
      group (five-day group, n = 27); a three day/week walking group (three-day group,
      n = 27) or a sedentary group (control group, n = 25). SETTING: Community-based
      intervention. PARTICIPANTS: Women who were postmenopausal, over 50 years old,
      sedentary, not on hormone replacement therapy, nonsmokers, physically capable of
      exercising, without clinical signs of cardiovascular, pulmonary or metabolic
      disease, and not on medication that would affect iron metabolism. In addition,
      they had neither donated blood nor been transfused within the previous 12 months.
      All participants were screened volunteers who had responded to media
      advertisements. Seventy-nine participants met these criteria. Results are
      reported for 56 subjects (five-day group, n = 17; three-day group, n = 19;
      control group, n = 20) who completed the study. Their mean age was 61.3 +/- 5.8
      years. INTERVENTION: The five-day group and the three-day group walked an average
      of 279 +/- 20 and 171 +/- 7 mins/week, respectively. Participants were counselled
      not to change their dietary intake. MAIN RESULTS: Following 24 weeks of walking,
      mean serum ferritin decreased significantly in the five-day group (P < 0.03), but
      not in the three-day group (P < 0.09) compared with controls. CONCLUSIONS: The
      extent of physical activity required to elicit a decrease in stored iron in
      postmenopausal women was determined. This may be clinically significant because
      stored iron increases significantly following menopause and excess stored iron
      have been cited as risk factors for coronary artery disease.

PMID- 8987966
TI  - Extracellular matrix and cardiovascular diseases.
AB  - Extracellular matrix (ECM) in the heart and vascular wall includes fibrous
      proteins and proteoglycans. Fibrous proteins are classified within two
      categories: structural (collagen and elastin) and adhesive molecules (laminin and
      fibronectin). These ECM components are important in maintenance of both structure
      and function of the heart and vascular tissues. Myocardial infarction,
      hypertrophy, hypertension and heart failure are well known to be associated with
      progressive cardiac fibrosis. Vascular hypertrophy and thickening has been
      associated with the pathological series of events that attends both hypertension
      and restenosis. The accumulation of ECM in the cardiovascular system plays an
      important role in the development of heart failure after myocardial infarction
      and hypertension, as well as in vascular hypertrophy and restenosis. Angiotensin
      II (angiotensin) and transforming growth factor beta 1 are known to play a role
      in signalling the abnormal accumulation of ECM in these cardiovascular diseases.
      Administration of angiotensin-converting enzyme inhibitor or angiotensin receptor
      type 1 antagonist is associated with regression of cardiac hypertrophy and
      fibrosis as well as vascular hypertrophy.

PMID- 8987967
TI  - Primary repair of Fallot's tetralogy in an older adult: a 20-year follow-up.
AB  - A patient with tetralogy of Fallot who presented at 58 years of age is described.
      Following surgical intracardiac repair he had 20 years of improved functional
      capacity. Though such surgery is now usually performed in infancy, the literature
      indicates that surgical correction of tetralogy of Fallot in appropriate adults
      is associated with low mortality and good long-term results.

PMID- 8987968
TI  - Ambulatory blood pressure monitoring: guidelines for use in clinical practice.
AB  - Ambulatory blood pressure monitoring is rapidly becoming an integral part of the
      diagnosis and management of hypertensive patients, particularly in major urban
      Canadian centres. To date, there have been several attempts to define the
      indications for ambulatory blood pressure monitoring, the most recent coming from
      an ad hoc panel of the American Society of Hypertension. This panel developed an
      algorithm for diagnosing persistent hypertension using office, home and
      ambulatory blood pressure readings. A revised algorithm tailored to the Canadian
      health care setting is proposed for implementing ambulatory blood pressure
      monitoring in the diagnosis of hypertension. Concerns about the term 'white coat'
      hypertension are discussed and the concept of a white coat effect for both
      untreated and treated patients is presented. There is preliminary evidence that
      patients who have a white coat component to their office readings experience
      fewer cardiovascular outcomes than do those with more persistent ambulatory
      hypertension. Recommendations from the ad hoc committee of the American Society
      of Hypertension provide a practical basis for using ambulatory blood pressure
      monitoring in clinical practice in Canada.

PMID- 8987969
TI  - Unstable angina--report from a Canadian expert roundtable.
AB  - Unstable angina is generally considered to encompass a spectrum of symptomatic
      manifestations of ischemic heart disease, intermediate between stable angina and
      acute myocardial infarction. Approximately 75,000 Canadians are hospitalized
      yearly with unstable angina. The pathophysiology of unstable angina is still
      imperfectly understood, but is related to the same pathophysiological factors
      underlying myocardial infarction and sudden cardiac death. In March 1995 a group
      of Canadian cardiologists met to review the current understanding of unstable
      angina and to define a Canadian approach to this common problem. Important issues
      and questions regarding the diagnosis and management of unstable angina were
      defined. The objective was to outline approaches to the management of unstable
      angina that would be appropriate in Canada. Topics discussed included definition,
      incidence, clinical presentations, pathophysiology, initial diagnostic and risk
      stratification approaches, acute medical management, role of invasive
      interventions and long term management.

PMID- 8987970
TI  - Pathophysiology and treatment of cocaine toxicity: implications for the heart and
      cardiovascular system.
AB  - OBJECTIVE: To review the data on pharmacology, pathophysiology and treatment of
      cocaine toxicity, with particular relevance to the heart and cardiovascular
      system. DATA SOURCE AND STUDY SELECTION: Published epidemiology, laboratory and
      clinical studies on the pharmacology, electrophysiology and pathophysiology of
      cocaine toxicity and its treatment. MAIN RESULTS: Cocaine toxicity-related
      morbidity and mortality are frequent due to the potent pharmacological effects of
      the drug as an indirect-acting sympathomimetic agent and its class I
      antiarrhythmic property paradoxically inducing pro-arrhythmia. The cardiac and
      cardiovascular toxic effects of cocaine include various degrees of myocardial
      ischemia, cardiac arrhythmias, cardiotoxicity, hypertensive effects,
      cerebrovascular effects and a hypercoagulable state. Treatment of cocaine
      toxicity must be based on the multiple factors leading to the toxicity. Sodium
      bicarbonate appears to have an important role in the acute setting with
      conduction abnormalities, seizures or acidosis. Unopposed alpha-stimulation
      provided by beta-blockade should be avoided. Central nervous system
      hyperexcitability should be treated with diazepam. The use of calcium antagonists
      appears logical. CONCLUSION: Cocaine is an alkaloid with widespread illicit use.
      The rationale for treating acute cocaine intoxication has become clearer and more
      logical with increased knowledge of its mechanisms of action.

PMID- 8987971
TI  - An essential binding surface for ShK toxin interaction with rat brain potassium
      channels.
AB  - An "Ala scan" analysis of ShK toxin, a 35-residue basic peptide possessing three
      disulfide bonds, identifies seven side chains which influence binding to brain
      delayed rectifier potassium channels. Additional analogs were synthesized and
      tested to further decipher the roles of these residues, particularly Tyr23. The
      inhibitory effects of these analogs on 125I-labeled dendrotoxin binding to rat
      brain membranes showed that replacement of Tyr23 with Ala drastically lowered the
      affinity of the toxin for the Kv1.2 channels. Ala substitution of Phe27 reduced
      potency more than 15-fold. Monosubstituted Ala analogs for Ile7, Ser20, or Lys30
      each displayed 5-fold reductions in potency. Thus, aromaticity at position 23 is
      important for effective delayed rectifier brain K channel binding. In contrast,
      the aromatic residue at position 27 was not critical, since cyclohexylalanine
      substitution increased affinity. The solution structure of ShK toxin clusters
      Ile7, Arg11, Ser20, Lys22, Tyr23, and Phe27 in close proximity, forming the
      potassium channel binding surface of the toxin. We propose an essential binding
      surface on the toxin in which Lys22 and Tyr23 are major contributors, through
      ionic and aromatic (hydrophobic) interactions, with the potassium channel.

PMID- 8987973
TI  - Disruption of the active site solvent network in carbonic anhydrase II decreases
      the efficiency of proton transfer.
AB  - The importance of maintaining the active site water network for efficient proton
      transfer was investigated by substituting amino acids of varying size at position
      65 in carbonic anhydrase II (including four amino acids found in other CA
      isozymes, F, L, S, and T, and two amino acids that do not occur naturally at
      position 65, G and H) and measuring the rate constants for the proton transfer
      reactions in the variant carbonic anhydrases. Intramolecular proton transfer
      between zinc-bound water and H64 is significantly inhibited by the introduction
      of bulky residues at position 65; kcat for CO2 hydration decreases up to 26-fold,
      comparable to the observed decrease in intramolecular proton transfer caused by
      removal of H64 [Tu, C., Silverman, D. N., Forsman, C., Jonsson, B.-H., &
      Lindskog, S. (1989) Biochemistry 28, 7913-7918]. Intermolecular proton transfer
      between protonated H64 and external buffer is also inhibited, although to a
      lesser degree. Furthermore, an alternative proton transfer pathway, consisting of
      an active site solvent-mediated proton transfer from zinc-water to imidazole
      buffer, is inhibited in the A65F, A65L, and A65H CAII variants. Therefore, the
      active solvent bridge between zinc-bound water and H64 is disrupted by
      substitutions at position 65. The inhibition of proton transfer reactions
      correlates with the disruption of the crystallographically observed solvent
      network in the CA active site and rotation of the proton acceptor, H64 [Scolnick,
      L. R., & Christianson, D. W. (1996) Biochemistry 35, 16429-16434], suggesting
      that this solvent network, including water molecules 292, 264, and 369, or a
      structurally related network, forms the proton transfer pathway in CAII for both
      intramolecular proton transfer and stimulation of proton transfer in imidazole
      buffers.

PMID- 8987972
TI  - Biosynthesis of 3,6-dideoxyhexoses: in vivo and in vitro evidence for protein
      protein interaction between CDP-6-deoxy-L-threo-D-glycero-4-hexulose 3-dehydrase
      (E1) and its reductase (E3).
AB  - CDP-6-deoxy-L-threo-D-glycero-4-hexulose 3-dehydrase (E1), together with its
      reductase (E3), catalyzes a novel deoxygenation reaction essential for the
      biosynthesis of 3,6-dideoxyhexoses. In an attempt to gain evidence substantiating
      the E1.E3 complex formation as a prerequisite for the C-3 deoxygenation activity,
      we have carried out experiments to study the interaction between these two
      proteins. The detection of a new species when a mixture of E1 and E3 was analyzed
      by size-exclusion chromatography was the initial indication supporting the
      proposed complex formation. Additional evidence for the expected complex
      formation was provided by the change of the CD spectrum of E1 upon its coupling
      with E3. The fact that the catalytic efficiency of this system is limited by the
      quantity of one enzyme, which becomes catalytically competent only after coupling
      with the second enzyme, further illustrated the importance of such a complex
      formation to the deoxygenation activity. By using the two-hybrid system which
      scores for interactions between two proteins coexpressed in yeast, the E1.E3
      complex formation in vivo was also firmly established. These results, when
      considered with the incompatibility of other electron transfer proteins as
      replacements for E3 in this electron relay, nicely demonstrated the specificity
      of the E1-E3 recognition. The apparent dissociation constant of the E1.E3 complex
      formed in rapid equilibrium was estimated to be 288 +/- 22 nM from the
      correlation between the initial rate of the overall reaction and the
      concentration of one protein component, and the stoichiometry between E3 and E1
      of this complex was deduced as 1.7. Interestingly, while the conformation of the
      E1.E3 complex was sensitive to the salt concentration in the buffer, the decrease
      in the catalytic activity at high ionic strength was most likely due to the
      retardation of the electron transfer mediated by E3. In conjunction with early
      mechanistic studies, the present data establish the significance of the E1.E3
      complex formation for catalysis and, consequently, corroborate the mechanism
      proposed for the overall deoxygenation process.

PMID- 8987974
TI  - X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II
      reveal the structural basis of compromised proton transfer in catalysis.
AB  - The three-dimensional structures of A65F, A65L, A65H, A65T, A65S, and A65G human
      carbonic anhydrase II (CAII) variants have been solved by X-ray crystallographic
      methods to probe the importance of residue 65 and the structural implications of
      its evolutionary drift in the greater family of carbonic anhydrase isozymes.
      Structure-activity relationships in this series of CAII variants are correlated
      with those established for other carbonic anhydrase isozymes. We conclude that a
      bulky side chain at position 65 hinders the formation of an effective solvent
      bridge between zinc-bound water and H64 and thereby hinders solvent-mediated
      proton transfer between these two groups [Jackman, J. E., Merz, K. M., Jr., &
      Fierke, C. A. (1996) Biochemistry 35, 16421-16428]. Despite the introduction of a
      polar hydroxyl group at this position, smaller side chains such as serine or
      threonine substituted for A65 do not perturb the formation of a solvent bridge
      between H64 and zinc-bound solvent. Thus, the evolution of residue 65 size is one
      factor affecting the trajectory of catalytic proton transfer.

PMID- 8987975
TI  - The active state of the AT1 angiotensin receptor is generated by angiotensin II
      induction.
AB  - In the current model of receptor activation, the given hormone is not involved in
      the conversion of the inactive receptor (R) to the fully active state (R*).
      Rather, it preferentially selects the activated receptor conformation, thereby
      shifting the equilibrium toward R*. The hormone angiotensin II (Ang II) contains
      two residues, Tyr4 and Phe8, that are essential for agonism. We show that the
      conserved Asn111 in transmembrane helix III of the AT1 angiotensin receptor
      directly interacts with the Tyr4 side chain. A decrease in the size of the Asn111
      side chain induces an intermediate activated receptor conformation (R'). The Ang
      II analogue [Sar1,Ile4,Ile8]Ang II fully activates the N111G mutant, indicating
      that either the transition from R' to R* or the stabilization of the R* state
      requires binding by Ang II but not its Tyr4 and Phe8 side chains. In contrast,
      [Sar1,Ile4,Ile8]Ang II binds to but does not activate the wild-type AT1 receptor
      (R), suggesting that in the wild-type receptor spontaneous occurrence of R' and
      R* states is rare. Thus, Ang II through interactions involving Tyr4 and Phe8
      induces a transition from R to R' and through unspecified interactions induces
      transition from R' to R* states rather than stabilizing the spontaneously
      generated R* state by "conformational, selection".

PMID- 8987976
TI  - Kinetically controlled folding of the serpin plasminogen activator inhibitor 1.
AB  - The serpin plasminogen activator inhibitor 1 (PAI-1) folds into an active
      structure and then converts slowly to a more stable, but low-activity, "latent"
      conformation [Hekman, C. M., & Loskutoff, D. J. (1985) J. Biol. Chem. 260, 11581
      11587]. Thus, the folding of PAI-1 is apparently under kinetic control. We have
      determined the urea denaturation and refolding transitions of both latent and
      active PAI-1 proteins by using intrinsic tryptophan fluorescence. While folding
      of active PAI-1 is reversible, the denaturation and refolding of latent PAI-1 are
      not. Instead, denatured latent PAI-1 refolds in lower concentrations of urea to
      give the active protein. Thus, the high-stability latent conformation is
      kinetically inaccessible over a range of urea concentrations. Complete
      denaturation of latent PAI-1 occurs at 5.5 M urea [delta G(H2O) approximately 21
      kcal] whereas active PAI-1 denatures in only 3.8 M urea [delta G(H2O)
      approximately 12 kcal]. The fluorescence emission profile, as a function of urea
      of both the active and latent forms of the protein, reveals intermediates with
      partial structure. Circular dichroism measurements and limited protease digestion
      with Lys-C suggest that the intermediate in the denaturation of latent PAI-1
      retains most of the secondary structure of the fully folded protein, whereas the
      intermediate in the denaturation of active PAI-1 exhibits significant loss of
      secondary structure. The Lys-C digestion patterns show that the active protein is
      more susceptible to proteolysis near sheet A than is the latent form. The studies
      suggest a model for the kinetically controlled folding pathway of PAI-1.

PMID- 8987977
TI  - Protein engineering thrombin for optimal specificity and potency of anticoagulant
      activity in vivo.
AB  - Previous alanine scanning mutagenesis of thrombin revealed that substitution of
      residues W50, K52, E229, and R233 (W60d, K60f, E217, and R221 in chymotrypsinogen
      numbering) with alanine altered the substrate specificity of thrombin to favor
      the anticoagulant substrate protein C. Saturation mutagenesis, in which residues
      W50, K52, E229, and R233 were each substituted with all 19 naturally occurring
      amino acids, resulted in the identification of a single mutation, E229K, that
      shifted the substrate specificity of thrombin by 130-fold to favor the activation
      of the anticoagulant substrate protein C over the procoagulant substrate
      fibrinogen. E229K thrombin was also less effective in activating platelets (18
      fold), was resistant to inhibition by antithrombin III (33-fold and 22-fold in
      the presence and absence of heparin), and displayed a prolonged half-life in
      plasma in vitro (26-fold). Thus E229K thrombin displayed an optimal phenotype to
      function as a potent and specific activator of endogenous protein C and as an
      anticoagulant in vivo. Upon infusion in Cynomolgus monkeys E229K thrombin caused
      an anticoagulant effect through the activation of endogenous protein C without
      coincidentally stimulating fibrinogen clotting and platelet activation as
      observed with wild-type thrombin. In addition, E229K thrombin displayed enhanced
      potency in vivo relative to the prototype protein C activator E229A thrombin.
      This enhanced potency may be attributable to decreased clearance by antithrombin
      III, the principal physiological inhibitor of thrombin.

PMID- 8987978
TI  - Combinatorial mutagenesis and structural simulations in the environment of the
      redox-active tyrosine YZ of photosystem II.
AB  - Tyr161 of the D1 protein (Yz) is a redox component closely associated with the
      water-oxidizing complex of photosystem II. Yz reduces the primary donor P680+,
      and Yzox is then rereduced by the manganese cluster that oxidizes water. We aimed
      to investigate whether water oxidation by P680+ could occur through an
      alternative pathway in the absence of Tyr161. For this purpose, combinatorial
      mutagenesis was performed in residues presumed to be in the environment of
      Tyr161. Full sequence degeneracy was introduced in two regions of the D1 protein:
      at codons 157, 158, 160, 162, 163, 164, and 165, which are close to Yz by
      sequence, and at codons 186-191 which are assumed to be close to Yz in the
      tertiary structure; at position 161, the nucleotide combinations were designed to
      not give rise to a Tyr codon. The combinatorial DNA mixture was used to transform
      an obligate photoheterotrophic mutant (Y161W) of the cyanobacterium Synechocystis
      sp. PCC 6803, in which Trp at position 161 impairs photosynthetic activity.
      Transformants were selected in which photoautotrophic growth was restored,
      resulting in 11 viable mutants. In all of these mutants, however, a Tyr codon was
      found at position 161, introduced either by complex repair processes or as a
      result of PCR-induced mutations. Additional mutations found in residues
      neighboring Tyr161 mostly retained photosystem II properties similar to those of
      wild type. However, in two of these mutants, FVEYPI and FLVYNI, photoautotrophic
      growth was impaired and the relative variable fluorescence was reduced. Computer
      simulations of the environment of Yz suggest that the position of Tyr161 varies
      with respect to some neighboring residues without major functional consequences.
      We conclude that Tyr161 fulfills a critical role through its chemical nature and
      positioning and that this function cannot be substituted by another residue at a
      nearby position.

PMID- 8987979
TI  - Effects of mutations in plastocyanin on the kinetics of the protein rearrangement
      gating the electron-transfer reaction with zinc cytochrome c. Analysis of the
      rearrangement pathway.
AB  - We study, by flash kinetic spectrophotometry on the microsecond time scale, the
      effects of ionic strength and viscosity on the kinetics of oxidative quenching of
      the triplet state of zinc cytochrome c (3Zncyt) by the wild-type form and the
      following nine mutants of cupriplastocyanin: Leu12Glu, Leu12Asn, Phe35Tyr,
      Gln88Glu, Tyr83Phe, Tyr83His, Asp42Asn, Glu43Asn, and the double mutant
      Glu59Lys/Glu60Gln. The unimolecular rate constants for the quenching reactions
      within the persistent diprotein complex, which predominates at low ionic
      strengths, and within the transient diprotein complex, which is involved at
      higher ionic strengths, are equal irrespective of the mutation. Evidently, the
      two complexes are the same. In both reactions, the rate-limiting step is
      rearrangement of the diprotein complex from a configuration optimal for docking
      to the one optimal for the subsequent electron-transfer step, which is fast. We
      investigate the effects of plastocyanin mutations on this rearrangement, which
      gates the overall electron-transfer reaction. Conversion of the carboxylate
      anions into amide groups in the lower acidic cluster (residues 42 and 43),
      replacement of Tyr83 with other aromatic residues, and mutations in the
      hydrophobic patch in plastocyanin do not significantly affect the rearrangement.
      Conversion of a pair of carboxylate anions into a cationic and a neutral residue
      in the upper acidic cluster (residues 59 and 60) impedes the rearrangement.
      Creation of an anion at position 88, between the upper acidic cluster and the
      hydrophobic patch, facilitates the rearrangement. The rate constant for the
      rearrangement smoothly decreases as the solution viscosity increases,
      irrespective of the mutation. Fittings of this dependence to the modified
      Kramers's equation and to an empirical equation show that zinc cytochrome c
      follows the same trajectory on the surfaces of all the plastocyanin mutants but
      that the obstacles along the way vary as mutations alter the electrostatic
      potential. Mutations that affect protein association (i.e., change the binding
      constant) do not necessarily affect the reaction between the associated proteins
      (i.e., the rate constant) and vice versa. All of the kinetic and thermodynamic
      effects and noneffects of mutations consistently indicate that in the protein
      rearrangement the basic patch of zinc cytochrome c moves from a position between
      the two acidic clusters to a position at or near the upper acidic cluster.

PMID- 8987980
TI  - Elimination of the hydrolytic water molecule in a class A beta-lactamase mutant:
      crystal structure and kinetics.
AB  - Two site-directed mutant enzymes of the class A beta-lactamase from
      Staphylococcus aureus PC1 were produced with the goal of blocking the site that
      in the native enzyme is occupied by the proposed hydrolytic water molecule. The
      crystal structures of these two mutant enzymes, N170Q and N170M, have been
      determined and refined at 2.2 and 2.0 A, respectively. They reveal that the side
      chain of Gln 170 displaces the water molecule, whereas that of Met170 does not.
      In both cases, the catalytic rates with benzylpenicillin are reduced by 10(4)
      compared with the native enzyme. With nitrocefin, the N170Q mutant enzyme
      exhibits an approximately 800-fold reduced rate compared with the native enzyme
      and in addition, a fast initial burst with stoichiometry of 1 mol of degraded
      nitrocefin/mol of enzyme. Stopped-flow kinetic experiments establish that the
      rate constant of the burst is 250 s-1, a value comparable with the rate of
      acylation of the native enzyme. Two structurally based mechanisms that explain
      the kinetic properties of the N170Q beta-lactamase are proposed, both invoking a
      deacylation-impaired enzyme due to the elimination of the hydrolytic water
      molecule. The catalytic rate of the N170M mutant enzyme with nitrocefin is
      reduced by approximately 50-fold compared with the native enzyme, and the slow
      progressive inhibition that is revealed indicates that the hydrolysis proceeds
      via a branched pathway mechanism. This is consistent with the structural data
      that show that the water site is preserved and that Met170 occupies part of the
      space that is required for substrate binding. The short contacts between the
      substrate and the enzyme may lead to structure perturbation and inactivation.

PMID- 8987981
TI  - Mechanistic interpretation of tryptophan fluorescence quenching in the time
      courses of glutamate dehydrogenase catalyzed reactions.
AB  - We have related the ratios of the protein fluorescence quenching and nucleotide
      absorbance time courses for the glutamate dehydrogenase catalyzed oxidative
      deamination of L-glutamate to identify the occurrence and sequential location of
      a previously demonstrated charge-transfer intermediate. Static studies showed the
      major portion of the fluorescence quenching signal to be due to radiationless
      singlet energy transfer from tryptophan to reduced coenzyme chromophores and that
      conformational changes contribute little to this signal. The ratio approach
      applied to the transient time courses shows correspondingly that, over most of
      the time range, the fluorescence quenching signal provides a quantitative measure
      of the sum of all posthydride transfer species. However, it also indicates the
      very early occurrence of a species of anomalous optical properties for the
      reaction catalyzed by the Clostridium symbiosum enzyme as well as that from
      bovine liver. Transient-state kinetic isotope effect time courses of both the
      fluorescence and the absorbance signals confirm that this species must be the
      prehydride charge-transfer complex in both enzyme reactions. Kinetic analysis of
      alpha-deuterio- and alpha-protio-L-glutamate reaction time courses proves the
      kinetic competence of the assignments. These results also demonstrate that the
      intramolecular transfer of a proton from the alpha-amino group of the substrate
      to an immediately adjacent aspartate carboxylate group on the enzyme is an
      obligatory initial event in the reactions catalyzed by both enzyme species, even
      though the occurrence of protein release from a critical lysine residue to the
      solvent occurs at different phases in those two reactions. The abnormally low
      intrinsic KIE required to simulate both the alpha-deuterio-L-glutamate reaction
      and its protio counterpart implies that the transition state of the hydride
      transfer step must be highly asymmetric.

PMID- 8987983
TI  - A 19F-NMR study of the equilibrium unfolding of membrane-associated D-lactate
      dehydrogenase of Escherichia coli.
AB  - Partially folded protein intermediates have been observed by 19F-NMR spectroscopy
      during the equilibrium unfolding of the membrane-associated D-lactate
      dehydrogenase (D-LDH) of Escherichia coli by a denaturant, guanidine
      hydrochloride (Gdn.HCl). The results from 19F-NMR and circular dichroism
      spectroscopic studies suggest that the intermediates observed at low Gdn.HCl
      concentrations (< 3.5 M) exhibit features similar to "molten globules" that
      contain considerable amounts of secondary and tertiary structure. The results of
      19F-NMR studies on 5F-Trp-labeled D-LDH, such as the chemical shift changes,
      nuclear Overhauser effect, and solvent-induced isotopic shift effect, show that
      different regions of D-LDH unfold nonuniformly in Gdn.HCl in the presence of
      lysophosphatidylcholine. The polypeptide appears to unfold in a general order
      from the carboxyl end to the amino end, in agreement with previous findings from
      our laboratory that the carboxyl-terminal region of D-LDH is largely exposed to
      the solvent while the amino-terminal region is buried in the protein core. The
      structure of the partially unfolded intermediate forms of D-LDH is stabilized in
      the presence of lipid-like detergents, such as lysophosphatidylcholine.

PMID- 8987982
TI  - The enolase superfamily: a general strategy for enzyme-catalyzed abstraction of
      the alpha-protons of carboxylic acids.
AB  - We have discovered a superfamily of enzymes related by their ability to catalyze
      the abstraction of the alpha-proton of a carboxylic acid to form an enolic
      intermediate. Although each reaction catalyzed by these enzymes is initiated by
      this common step, their overall reactions (including racemization, beta
      elimination of water, beta-elimination of ammonia, and cycloisomerization) as
      well as the stereochemical consequences (syn vs anti) of the beta-elimination
      reactions are diverse. Analysis of sequence and structural similarities among
      these proteins suggests that all of their chemical reactions are mediated by a
      common active site architecture modified through evolution to allow the enolic
      intermediates to partition to different products in their respective active sites
      via different overall mechanisms. All of these enzymes retain the ability to
      catalyze the thermodynamically difficult step of proton abstraction. These
      homologous proteins, designated the "enolase superfamily", include enolase as
      well as more metabolically specialized enzymes: mandelate racemase, galactonate
      dehydratase, glucarate dehydratase, muconate-lactonizing enzymes, N-acylamino
      acid racemase, beta-methylaspartate ammonia-lyase, and o-succinylbenzoate
      synthase. Comparative analysis of structure-function relationships within the
      superfamily suggests that carboxyphosphonoenolpyruvate synthase, another member
      of the superfamily, does not catalyze the reaction proposed in the literature but
      catalyzes an enolase-like reaction instead. The established and deduced structure
      function relationships in the superfamily allow the prediction that other
      apparent members of the family for which no catalytic functions have yet been
      assigned will also perform chemistry involving abstraction of the alpha-protons
      of carboxylic acids.

PMID- 8987984
TI  - Effect of the apolipoprotein A-I and surface lipid composition of reconstituted
      discoidal HDL on cholesterol efflux from cultured fibroblasts.
AB  - Five series of reconstituted discoidal HDL (LpA-I) particles have been prepared,
      and their constituents, apolipoprotein A-I (apoA-I), 1-palmitoyl-2
      oleoylphosphatidylcholine (POPC), unesterified cholesterol (UC),
      phosphatidylinositol (PI), or sphingomyelin (SM), have been systematically varied
      to elucidate the relationship between HDL composition and cholesterol efflux from
      non-cholesterol-loaded human skin fibroblasts. The physical properties, such as
      hydrodynamic diameters, alpha-helix contents, and surface potentials, of these
      LpA-I have been measured and related to the ability of the LpA-I to accept
      cellular cholesterol. The results show that for LpA-I particles containing 2, 3,
      or 4 apoA-I per particle, Lp4A-I are the best acceptors of cellular cholesterol,
      followed by Lp3A-I and then Lp2A-I particles. Discoidal Lp2A-I with variations in
      POPC content, from 121 to 266 mol/particle; show no difference in their abilities
      to promote cholesterol efflux. Similarly, inclusion of 7 and 15 mol of free
      cholesterol to Lp2A-I also does not affect their ability to accept cellular
      cholesterol. However, increasing the content of either PI or SM, up to 20
      mol/particle, is associated with significantly increased abilities of the LpA-I
      to promote cholesterol efflux. The efflux of cellular cholesterol to discoidal
      LpA-I particles is independent of specific changes in apoA-I conformation and
      charge, but appears to be positively related to major changes in the size of the
      lipoprotein particle. The study suggests that in contrast to interlipoprotein
      cholesterol transfers, the efflux of cholesterol from cultured fibroblasts is
      less sensitive to factors that affect the frequency of molecular collisions and
      more dependent on the ability of an HDL particle to absorb and retain cholesterol
      molecules. Since SM and PI appear to modulate this adsorption/desorption of
      cholesterol to HDL, variations in the concentration of these lipids within HDL
      would be expected to affect plasma cholesterol homeostasis.

PMID- 8987985
TI  - Structure-function analysis of liver-type (GLUT2) and brain-type (GLUT3) glucose
      transporters: expression of chimeric transporters in Xenopus oocytes suggests an
      important role for putative transmembrane helix 7 in determining substrate
      selectivity.
AB  - The liver-type (GLUT2) and brain-type (GLUT3) human facilitative glucose
      transporters exhibit distinct kinetics (K(m) values for deoxyglucose transport of
      11.2 +/- 1.1 and 1.4 +/- 0.06 mM, respectively) and patterns of substrate
      transport (GLUT2 is capable of D-fructose transport, GLUT3 is not) [Gould, G. W.,
      Thomas, H. M., Jess, T. J., & Bell, G. I. (1991) Biochemistry 30, 5139-5145]. We
      have generated a range of chimeric glucose transporters composed of regions of
      GLUT2 and GLUT3 with a view to identifying the regions of the transporter which
      are involved in substrate recognition and binding. The functional characteristics
      of these chimeras were determined by expression in Xenopus oocytes after
      microinjection of cRNA. Replacement of the region from the start of putative
      transmembrane helix 7 to the C-terminus of GLUT3 with the corresponding region
      from GLUT2 results in a chimera with the ability to transport fructose and
      exhibits a K(m) for 2-deoxyglucose transport of close to that observed for wild
      type GLUT2 (8.3 +/- 0.3 mM compared to 11.2 +/- 1.1 mM). Replacement of the
      region in GLUT3 from the end of helix 7 to the C-terminus with the corresponding
      region from GLUT2 resulted in a species which was unable to transport fructose
      and whose K(m) for 2-deoxyglucose was indistinguishable from wild-type GLUT3. We
      have determined the affinity for 2-deoxyglucose, D-fructose, and D-galactose of
      these and other chimeras. In addition, the Ki for maltose, a competitive
      inhibitor of 2-deoxyglucose transport, which binds to the exofacial sugar binding
      site was determined for these chimeras. The results obtained support a model in
      which the seventh putative transmembrane-spanning helix is intimately involved in
      the selection of transported substrate and in which this region plays an
      important role in determining the K(m) for 2-deoxyglucose. Additional data is
      presented which suggests that a region between the end of putative transmembrane
      helix 7 and the end of helix 10, together with sequences in the N-terminal half
      of the protein may also participate in substrate recognition and transport
      catalysis.

PMID- 8987986
TI  - Calcium binding properties of synthetic gamma-carboxyglutamic acid-containing
      marine cone snail "sleeper" peptides, conantokin-G and conantokin-T.
AB  - Total chemical synthesis of two Conus-derived peptides, conantokin-G (con-G), a
      17-residue polypeptide containing five residues of gamma-carboxyglutamic acid
      (Gla), and conantokin-T (con-T), a 21-residue polypeptide possessing four
      residues of Gla, was accomplished. Calcium binding isotherms were obtained for
      each peptide, and these differed considerably from each other. The binding
      isotherm for con-G was complex and could only be fit to degenerate models
      involving multiple Ca2+ binding sites. The data for Ca2+ binding to con-T was
      uniquely fit to a simple one-site model. In the case of con-G, circular dichroism
      (CD) studies revealed a polypeptide without observable alpha-helicity in the
      absence of Ca2+ and a dramatic shift to a high degree of alpha-helix at
      saturating Ca2+ concentrations. In contrast, apo-con-T possessed significant
      alpha-helical structure, and saturation with Ca2+ produced a less substantial
      change in its alpha-helical content. Titrations with Ca2+ of the change in alpha
      helical content of con-T produced a C50 value for Ca2+ that was essentially the
      same as its Kd from direct binding studies, demonstrating that occupancy of the
      single macroscopic binding site resulted in the conformational change. Similar
      titrations with con-G provided a C50 value in concert with the Kd for binding of
      Ca2+ to this peptide. Moreover, in agreement with these particular Ca(2+)-induced
      structural changes, gel filtration analyses demonstrated significantly reduced
      hydrodynamic volumes of both of these polypeptides after saturation of their apo
      forms with Ca2+, with con-G showing a more pronounced change than con-T. One
      dimensional H-NMR spectra showed both line broadening and changes in chemical
      shifts of several peptide amide proton resonances after addition of Ca2+ to con
      G, again suggestive of a large Ca(2+)-induced conformational change in this
      polypeptide. A derivative of con-G was synthesized with all amino acids present
      in the D-configuration (D-con-G). This variant peptide displayed Ca2+ binding
      isotherms nearly identical to those of con-G and underwent a Ca(2+)-induced
      conformational change very similar to that of con-G. Intracranial injections of
      con-G and con-T in young (< 2 weeks) and older (3-4 weeks) mice produced the
      expected "sleep-like" and hyperactive effects, respectively. The variant, D-con
      G, was inactive in these assays. These studies demonstrate that synthetic con-G
      and con-T possess their expected bioactivities and undergo large and defined
      conformational alterations in the presence of Ca2+. We propose that binding of
      Ca2+ to these polypeptides contributes to their ability to adopt a defined
      conformation, and this divalent cation-dependent conformation is necessary for
      their neuroactivities.

PMID- 8987987
TI  - Structural requirements and thermodynamics of the interaction of proline peptides
      with profilin.
AB  - The binding to poly(L-proline) is used for the affinity purification of
      profilins, but little is known about the structural and thermodynamic aspects of
      the interaction. We used changes in the intrinsic fluorescence of profilin, CD
      spectroscopy, and isothermal titration calorimetry to assess how the size and
      composition of synthetic proline-rich peptides influence binding to Acanthamoeba
      and human profilins. Although a 6 residue type II poly(L-proline) helix can span
      the binding site, highest affinity binding is achieved by proline oligomers > or
      = 10 residues. Binding is stereospecific since (D-proline)11 does not bind. In 75
      mM KCI the dissociation equilibrium constant for poly(L-proline) is about 10
      microM proline decamer units for amoeba profilin and 20-30 microM for human
      profilin. Consistent with a significant hydrophobic component of the interaction,
      delta Cp is negative and higher salt concentrations enhance the affinity. No
      protons dissociate or bind during the interaction. Binding of poly(L-proline) is
      favored both entropically and enthalpically. Substitution of glycine in proline
      undecamers reduces affinity by about 1 kcal mol-1 for each substitution due to
      increased rotational freedom of the free peptides. Substitution of alanine has a
      similar effect. Disorder in the free peptides imparts an unfavorable entropic
      cost for immobilizing the substituted peptides on the binding site on profilin.

PMID- 8987989
TI  - Kinetics of gelsolin interaction with phalloidin-stabilized F-actin. Rate
      constants for binding and severing.
AB  - The kinetics of gelsolin interaction with actin filaments have been investigated
      using two fluorescent probes, tetramethylrhodamine isothiocyanate-labeled
      phalloidin bound to F-actin and N-(1-pyrenyl)iodoacetamide-labeled actin. We have
      also analyzed the F-actin severing by gelsolin using an assay for actin filaments
      which measures the polymerization rate of monomeric actin added to the gelsolin
      severed filaments. Phalloidin-stabilized actin filaments were used in order to
      minimize the depolymerization reaction and thus simplify the kinetic analysis.
      Because gelsolin activity is Ca(2+)-activated, experiments were conducted in the
      presence of 0.5 mM CaCl2 to ensure maximal activity. We show that the interaction
      of gelsolin with F-actin may be separated into two distinct kinetic phases which
      correspond to binding and severing events. Using a two-step model of gelsolin
      activity, we have determined that gelsolin binds to F-actin with an association
      rate constant of 2 x 10(7) M-1 s-1, dissociates with a rate constant in the range
      0.4-1.2 s-1, and subsequently severs phalloidin-stabilized F-actin with a first
      order rate constant of 0.25 s-1. Characterization of the binding and severing
      reactions will facilitate further investigation of gelsolin activity and its
      regulation.

PMID- 8987990
TI  - Mutational analysis of the role of the N terminus of actin in actomyosin
      interactions. Comparison with other mutant actins and implications for the cross
      bridge cycle.
AB  - Yeast actin mutants with acidic residues at the N terminus either neutralized
      (DNEQ) or deleted (delta-DSE) were used to assess the role of N-terminal acidic
      residues in the interactions of actin with myosin in the contractile cycle.
      Cosedimentation experiments revealed an approximately 3-fold decrease in the
      binding constant for DNEQ and delta-DSE actins to myosin subfragment-1 (S1)
      relative to that of wild type actin both in the presence of MgATP and in the
      absence of nucleotides (strong binding). DNEQ and delta-DSE actins protected S1
      from tryptic digestion as well as the wild type and rabbit actins. The activation
      of S1 ATPase by DNEQ and delta-DSE actins (up to 50 microM) was very low but
      increased greatly after cross-linking these mutant actins to S1 by dimethyl
      suberimidate. Thus, the increased dissociation of mutant actins from S1 in the
      presence of ATP is the main cause for the low acto-S1 ATPase activities. At low
      ionic strength conditions and in the presence of methylcellulose, the DNEQ and
      delta-DSE actins moved in the in vitro motility assays at a mean velocity similar
      to that of wild type actin (3.0 microns/s). Yet, the sliding velocity of the N
      terminal and D24A/D25A and E99A/E100A mutant actins decreased relative to that of
      the wild type at all levels of external load introduced into the assay and at low
      densities of heavy meromyosin (HMM) on the cover slip. This indicates a lower
      relative force generation with the mutant actins. In contrast, the force
      generated under the same conditions with the 4Ac mutant actin (with four acidic
      charges at the N terminus) was higher than with wild type actin. At higher-ionic
      strength conditions (I = 150 mM), the sliding of the DNEQ and delta-DSE as well
      as that of the D24A/D25A and E99A/E100A actins ceased even in the presence of
      methylcellulose, while I341A actin (deficient in strong binding to myosin) still
      moved. These results indicate the importance of electrostatic actomyosin
      interactions under physiological salt conditions and show functionally distinct
      roles for the different myosin binding sites on actin.

PMID- 8987988
TI  - Profilin and gelsolin stimulate phosphatidylinositol 3-kinase activity.
AB  - Actin-binding proteins such as profilin and gelsolin bind to phosphatidylinositol
      (PI) 4,5-bisphosphate (PI 4,5-P2) and regulate the concentration of monomeric
      actin. We report here that profilin and gelsolin stimulate PI 3-kinase-mediated
      phosphorylation of PI 4,5-P2 (lipid kinase activity) in a concentration-dependent
      manner. This effect is specific to profilin and gelsolin because other
      cytoskeletal proteins such as tau or actin do not affect PI 3-kinase activity. In
      addition to lipid kinase activity, PI 3-kinase also has protein kinase activity:
      it phosphorylates proteins (p85 subunit of PI 3-kinase). However, the protein
      kinase activity of PI 3-kinase was not affected in the presence of profilin.
      Kinetic analysis, as a function of varying concentrations of ATP and PI 4,5-P2,
      showed that profilin affects the Vmax of PI 3-kinase without affecting k(m).
      Profilin may also affect PI 3-kinase activity by its direct association to the
      enzyme because dot-blot analysis using antibody to glutathione S-transferase
      (GST) suggested that GST-85 kDa, a fusion protein of PI 3-kinase, binds to
      profilin. However, PI 3-kinase did not affect the actin-sequestering ability of
      profilin (determined by pyrene-labeled actin), which indicates that actin and p85
      do not share a common binding site on profilin. These studies suggest that
      profilin and gelsolin may control the generation of 3-OH phosphorylated
      phosphoinositides, which in turn may regulate the actin polymerization.

PMID- 8987991
TI  - Polymerization and in vitro motility properties of yeast actin: a comparison with
      rabbit skeletal alpha-actin.
AB  - Actin purified from the yeast (Saccharomyces cerevisae) was polymerized faster
      than rabbit skeletal alpha-actin by MgCl2. The two actins polymerized at similar
      rates in the presence of CaCl2. Yeast actin, up to 25 microM, was not polymerized
      by KCl (100-300 mM); the monovalent salt also inhibited the MgCl2-induced
      polymerization of actin. The local structure of the subdomain-2 region in yeast
      actin filaments was probed by subtilisin and trypsin digestions. Loop 38-52
      appeared more flexible and accessible to subtilisin in yeast than in rabbit
      actin. In contrast, tryptic digestions at Lys-61 and -68 occurred at the same
      rate for yeast and alpha-actin filaments. Modification of yeast actin by a
      sulfhydryl reagent CPM [7-(diethylamino)-3-(4'-maleimidophenyl)-4-methylcoumain]
      was specific to the Cys-374 residue; no labeling of a yeast actin mutant
      containing an alanine substitution for cysteine 374 was observed. The rates of
      Cys-374 labeling by CPM were similar for yeast and muscle actin, suggesting a
      similar environment for the C terminus in both polymers. In the in vitro motility
      assays, yeast actin required higher concentrations of heavy meromyosin (HMM) for
      its sliding than did the rabbit actin. At saturating concentrations of HMM, the
      sliding velocities of both actins were the same (3.0 microns/s). Relative forces
      generated by HMM with yeast and muscle actin were assessed by monitoring their in
      vitro motility in the presence of NEM-HMM load. The sliding of yeast actin was
      stopped at a level of external load (molar ratio NEM-HMM/HMM = 0.25) lower than
      that of muscle actin (NEM-HMM/HMM = 0.43), suggesting lower force production with
      yeast actin. These results are discussed in terms of the myosin cross-bridge
      cycle and actomyosin interactions.

PMID- 8987992
TI  - Interaction of deletion mutants of troponins I and T: COOH-terminal truncation of
      troponin T abolishes troponin I binding and reduces Ca2+ sensitivity of the
      reconstituted regulatory system.
AB  - The interaction between troponin I (TnI) and troponin T (TnT) remains the least
      understood binary interaction among the regulatory proteins of vertebrate
      striated muscle. To identify the specific binding domains of TnI and TnT and to
      evaluate the interactions of TnT with troponin C and tropomyosin (Tm), we
      generated an NH2-terminal fragment of human fast skeletal beta TnT (TnT1-201;
      residues 1-201) using site-directed mutagenesis. The mutant protein failed to
      bind to rabbit skeletal muscle TnI as judged by HPLC, showed reduced TnC binding
      and reduced ternary troponin (Tn) complex formation, and exhibited a much reduced
      Ca2+ sensitivity in the reconstituted regulatory system. It is shown that the
      amount of Tn complex formed by TnT1-201 rather than the activity of the mutant Tn
      complex affected this Ca2+ sensitivity. Binding of the mutant to Tm was similar
      to that of intact TnT. These results support the view that the COOH-terminal
      segment of TnT is necessary for binding to TnI and TnC and Ca2+ sensitivity in
      the thin filament, whereas its NH2-terminus strongly binds to Tm. To identify the
      regions of TnI which bind to muscle TnT, we used four recombinant fragments of
      fast skeletal muscle TnI containing amino acid residues 1-94 (TnI1-94), 1-120
      (TnI1-120), 96-181 (TnI96-181), and 122-181 (TnI122-181) and a synthetic peptide,
      TnI98-114, containing residues 98-114 corresponding to the inhibitory region.
      Only TnI1-120 showed weak binding to TnT but not to TnT1-201. These results
      suggest that (i) a region within the NH2-terminal 120 residues of TnI interacts
      with TnT and (ii) the COOH-terminal residues 202-258 of TnT contain the
      interaction site of TnI. Overall, our results also imply that residues 159-201
      constitute the smallest region of TnT which contributes to the Ca2+ sensitivity
      of actoS1 ATPase in a reconstituted regulatory system.

PMID- 8987993
TI  - Expression, zinc-affinity purification, and characterization of a novel metal
      binding cluster in troponin T: metal-stabilized alpha-helical structure and
      effects of the NH2-terminal variable region on the conformation of intact
      troponin T and its association with tropomyosin.
AB  - A repeating metal-binding (Cu2+ > Ni2+ > Zn2+ approximately Co2+) sequence
      [HE/AEAH]4 (Tx) has been recently identified in the NH2-terminal variable region
      of troponin T (TnT) isoforms specifically expressed in the breast but not leg
      muscles of the avian orders of Galliformes and Craciformes [Jin, J.-P., &
      Smillie, L. B. (1994) FEBS Lett. 341, 135-140]. In the present study, two
      expression plasmids were constructed to produce chicken TnT1 NH2-terminal
      fragments of 47 (N47) or 165 (N165) amino acids containing the Tx metal-binding
      cluster. The recombinant protein/peptide was expressed in Escherichia coli
      BL21(DE3)pLysS and purified by a highly effective Zn(2+)-affinity chromatography
      method. Amino acid analyses, NH2-terminal peptide sequencing, mass spectrometry
      and immunological identification confirmed the authenticity of the genetically
      engineered TnT fragments. In the presence of 2,2,2-trifluoroethanol, transition
      metals had significant effects on the secondary structure of TnT fragment N47, as
      shown by circular dichroism. N165 in non-denaturing buffer demonstrated alpha
      helical content comparable to previous data from rabbit fast skeletal TnT
      fragment T1. Zn(2+)-binding avidity of the metal-binding TnT and its fragments
      demonstrated tertiary relationships between the NH2-terminal variable region and
      the COOH-terminal segment of the intact TnT protein. Solid-phase protein-binding
      assays established that Zn(2+)-binding to the Tx cluster induces epitopic
      structure changes in this NH2-terminal segment, further affecting other epitopic
      structures of intact TnT as well as the function of TnT's tropomyosin binding
      sites. The results demonstrate that metal ion-binding to the Tx cluster
      reconfigures the overall conformation of TnT through structural relationships
      between the NH2-terminal variable region and other domains of the intact TnT
      molecule. Accordingly, the developmental and/or muscle type specific NH2-terminal
      structure of TnT isoforms may modulate the Ca(2+)-activation of muscle
      contraction.

PMID- 8987994
TI  - Creating RNA bulges: cleavage of RNA in RNA/DNA duplexes by metal ion catalysis.
AB  - The manipulation of a single-stranded RNA target by forming different
      RNA/antisense hybrids demonstrates the possibility of cleaving the RNA strand
      within duplexes. This was achieved using the sequence composition of the
      antisense oligonucleotide, an approach that results in various bulges [unpaired
      base(s)] in the RNA target, which is then cleavable at these specific bulge sites
      under free metal ion or metal complex catalysis. RNA cleavages promoted by metal
      ions were performed under mild conditions and characterized by separating the RNA
      fragments carrying end label. The observed products result from intramolecular
      transesterification causing RNA strand scission. No detectable cleavage of the
      RNA was observed with either a fully complementary RNA/antisense hybrid or a
      bulged base in the antisense strand. A molecular modeling study of the RNA
      backbone suggests that the local conformation of the RNA backbone at a bulge in
      such hybrid duplexes greatly facilitates the metal-assisted catalytic cleavage.
      Endonucleolytic RNA cleavage within an RNA/antisense hybrid by metal complexes
      attached to the antisense oligonucleotide might lead to a new approach in
      antisense technology with artificial ribonucleases which operate with catalytic
      turnover.

PMID- 8987995
TI  - A short autocomplementary sequence plays an essential role in avian sarcoma
      leukosis virus RNA dimerization.
AB  - Retroviral genomes consist of two identical RNA molecules joined noncovalently
      near their 5'-ends. Recently, two models have been proposed for RNA dimer
      formation on the basis of results obtained in vitro with human immunodeficiency
      virus type 1 RNA and Moloney murine leukemia virus RNA. It was first proposed
      that viral RNA dimerizes by forming an interstrand quadruple helix with purine
      tetrads. The second model postulates that RNA dimerization is initiated by a loop
      loop interaction between the two RNA molecules. In order to better characterize
      the dimerization process of retroviral genomic RNA, we analyzed the in vitro
      dimerization of avian sarcoma-leukosis virus (ASLV) RNA using different
      transcripts. We determined the requirements for heterodimer formation, the
      thermal dissociation of RNA dimers, and the influence of antisense DNA
      oligonucleotides on dimer formation. Our results strongly suggest that purine
      tetrads are not involved in dimer formation. Data show that an autocomplementary
      sequence located upstream from the splice donor site and within a major packaging
      signal plays a crucial role in ASLV RNA dimer formation in vitro. This sequence
      is able to form a stem-loop structure, and phylogenetic analysis reveals that it
      is conserved in 28 different avian sarcoma and leukosis viruses. These results
      suggest that dimerization of ASLV RNA is initiated by a loop-loop interaction
      between two RNA molecules and provide an additional argument for the ubiquity of
      the dimerization process via loop-loop interaction.

PMID- 8987996
TI  - Elucidation of the role of Arg 110 of murine leukemia virus reverse transcriptase
      in the catalytic mechanism: biochemical characterization of its mutant enzymes.
AB  - Based on the projected three-dimensional equivalence of conserved amino acids in
      the catalytic domains of DNA polymerases, we propose Arg 110 of MuLV RT to be an
      important participant in the catalytic mechanism of MuLV RT. In order to obtain
      evidence to support this proposition and to assess the functional importance of
      Arg 110, we carried out site directed mutagenesis of Arg 110 and replaced it with
      Lys, Ala, and Glu. The mutant enzymes were characterized with respect to their
      kinetic parameters, ability to bind template-primers, and the mode of DNA
      synthesis. All the three substitutions at 110 position resulted in severe loss of
      polymerase activity without any significant effect on the RNase H function. In
      spite of an approximately 1000-fold reduction in kcat of polymerase activity with
      three mutant enzymes, no significant reduction in the affinities for either
      template-primer or dNTP substrates was apparent. Mutant enzymes also did not
      exhibit significant sulfur elemental effect, implying that the chemical step,
      i.e., phosphodiester bond formation, was not defective. Examination of the mode
      of DNA synthesis by the mutant enzymes indicated a shift from processive to the
      distributive mode of synthesis. The mutants of R110 also displayed significant
      loss of pyrophosphorolysis activity. Furthermore, the time course of primer
      extension with mutant enzymes indicated severe reduction in the rates of addition
      of the first nucleotide and even further reduction in the addition of the second
      nucleotide. These results suggest that the rate limiting step for the mutant
      enzymes may be before and after the phosphodiester bond formation. Based on these
      results, we propose that Arg 110 of MuLV RT participates in the conformational
      change steps prior to and after the chemical step of polymerase reaction.

PMID- 8987997
TI  - Functional consequences and exonuclease kinetic parameters of point mutations in
      bacteriophage T4 DNA polymerase.
AB  - Three groups of T4 DNA polymerase mutants were prepared and characterized. In the
      first group, Ala and Asn were substituted for four acidic residues in the
      exonuclease domain that were chosen on the basis of their sequence alignment with
      the Klenow fragment from Escherichia coli DNA polymerase I. Two divalent metal
      ions required for catalyzing the 3'-5' exonuclease reaction are ligated by
      carboxyl groups from these conserved Asp and Glu residues. The Ala and Asn
      replacements have a profound effect on the exonuclease activity of T4 DNA
      polymerase and also have a significant, but less pronounced influence on its
      polymerase activity which is located in a domain distal to the exonuclease
      region. The kcat values for the exonuclease reaction were reduced by 3-4 orders
      of magnitude by these replacements, but the values of Km(app) did not differ
      greatly from the wild-type enzyme. The second group consists of replacements of
      other residues, that are conserved in the exonuclease domain of eukaryotic DNA
      polymerases, but do not contribute to divalent metal ion coordination. Many of
      these alterations resulted in decreased exonuclease and/or polymerase activity.
      Mutants in the third group have substitutions of conserved residues in the
      polymerase domain which diminished polymerase and altered exonuclease activities.
      Our results, combined with structural data on crystals of protein N388, a
      truncated form of T4 DNA polymerase (Wang et al., 1996), show that: (i) the
      reduction in the relative specific exonuclease activities of mutants in the first
      group was significantly less than that of mutants in the Klenow fragment, despite
      the nearly identical geometric arrangement of the metal liganding groups in two
      proteins; (ii) altered residues, that affect exonuclease and/or polymerase
      activities in mutants of the second group, cluster within a small area of the
      exonuclease domain, suggesting that this area may be directly or indirectly
      involved in polymerase activity; (iii) mutations in the third group, which affect
      polymerase and exonuclease activities, may participate in DNA and dNTP binding.
      Our results point to the functional interdependence of the polymerase and
      exonuclease domains in T4 DNA polymerase, a property not observed with the Klenow
      fragment.

PMID- 8987998
TI  - The phosphodiester bond 3' to a deoxyuridine residue is crucial for substrate
      binding for uracil DNA N-glycosylase.
AB  - Using the method of water-soluble carbodiimide-induced chemical ligation, four 27
      member oligodeoxyribonucleotides containing a pyrophosphate internucleotide bond
      near or adjacent to a deoxyuridine residue were prepared. Escherichia coli uracil
      DNA N-glycosylase (UDG) activity was found to be sensitive to the presence of an
      internucleotide pyrophosphate bond in both single- and double-stranded DNA. The
      rate of uracil excision from single-stranded DNA containing a pyrophosphate bond
      adjacent to the uracil residue, either 3' or 5', was 0.01% and 0.1% of the rate
      of uracil removal from control DNA without a pyrophosphate bond, respectively.
      The rate of uracil excision from duplex DNA containing a pyrophosphate bond 3' or
      5' to the uracil residue was also reduced, being 0.1% and 1% the rate of uracil
      removal from the corresponding duplex DNA control. Placing the pyrophosphate bond
      one nucleotide 5' or 3' away from the deoxyuridine in both single- and double
      stranded oligodeoxyribonucleotides provided much better substrates for UDG.
      Kinetic measurements showed that the pyrophosphate bond placed adjacent to the
      deoxyuridine residue drastically reduced the affinity of UDG toward the modified
      DNA substrate, with the greatest effect occurring when the pyrophosphate bond was
      3' adjacent to the deoxyuridine. The enzyme was able to excise a 3'-terminal
      uracil at the nicked site of a nicked duplex, DNA, provided that the terminal
      deoxyuridine was 3'-phosphorylated. The effect of the pyrophosphate bond on the
      substrate susceptibility of oligonucleotides containing deoxyuridine is discussed
      with respect to the mechanism of action of UDG.

PMID- 8987999
TI  - Frayed wires: a thermally stable form of DNA with two distinct structural
      domains.
AB  - In aqueous solutions containing mono- and divalent cations, the
      oligodeoxyribonucleotide d(A15G15) readily self-assembles into high-molecular
      weight species that resolve as discrete bands on native and denaturing
      electrophoresis gels. The complexes consist of an integer number of strands of
      d(A15G15), the number of strands range from one (the monomer) to greater than
      nine. The complexes form within a few minutes even at low concentrations (2
      microM strands) of d(A15G15). The relative concentration of species is determined
      by the solvent conditions. The complexes are resistant to standard denaturation
      conditions, 50% formamide heated to 95 degrees C for 2 min followed by
      electrophoresis in 7 M urea at 55 degrees C. In the proposed model for the
      oligomers and polymers of d(A15G15), several molecules of d(A15G15) interact via
      a stem of tetraplex structure formed by the guanine residues. The 15 guanine
      residues in the stem account for its high stability. The 5' end adenines form
      single-stranded arms that are displaced from the guanine-containing stem. The
      arms can participate in the formation of Watson-Crick base pairs with dT10 and
      other partially complementary oligodeoxyribonucleotides such as d(CT15).
      Engagement of the arms in interactions with other strands does not affect the
      distribution of the species between different conformations. On the other hand,
      the addition of the fully complementary oligodeoxyribonucleotide d(C15T15) to the
      polymer leads to the disappearance of the high-molecular weight complexes and
      results in the formation of a canonical Watson-Crick base-paired duplex. The type
      and concentration of the cation present in solution determine which conformation
      d(A15G15) will adopt. Divalent cations at millimolar concentrations lead to the
      formation of the polymer, while the presence of the monovalent cations stabilizes
      lower-molecular weight complexes consisting of two to six strands of d(A15G15).

PMID- 8988000
TI  - Fidelity of translesional synthesis past benzo[a]pyrene diol epoxide-2'
      deoxyguanosine DNA adducts: marked effects of host cell, sequence context, and
      chirality.
AB  - We have used a site-specific approach to investigate the mutagenic potential of
      (+)- and (-)-trans-anti-benzo[a]pyrene diol epoxide (BPDE) DNA adducts.
      Oligodeoxyribonucleotides (5'TCCTCCTG1G2-CCTCTC), modified at the exocyclic amino
      groups of G1 or G2, were incorporated into a single-stranded shuttle vector and
      introduced into Escherichia coli or simian kidney (COS) cells. This experimental
      system permits translesional synthesis to proceed in the absence of DNA repair.
      The presence of (+)- or (-)-BPDE-N2-dG adducts strongly inhibited translesional
      synthesis in E. coli; induction of cellular SOS functions reduced this blocking
      effect. Vectors containing (+)-BPDE adducts at G1 or G2 generated mutation
      frequencies of 19% and 3%, respectively; these values were not altered
      significantly by induction of SOS functions. In COS cells, (+)-BPDE-modified
      vectors generated mutation frequencies of 13% at G1 and 45% at G2. In E. coli,
      the (-)-BPDE adduct generated mutation frequencies of < or = 2% at G1 and G2 and,
      in COS cells, 13% at G1 and 21% at G2. The predominant mutations in E. coli and
      COS cells were G-->T transversions targeted to the site of the lesion; however,
      when G2 was modified, a significant number of targeted G-->A and G-->C mutations
      were observed in COS cells. We conclude from this study that (+)-and (-)-BPDE-N2
      dG adducts pair preferentially to dCMP and dAMP during translesional synthesis in
      a process that is strongly influenced by the stereochemistry of the adduct, by
      the bases flanking the lesion, and by host cell factors.

PMID- 8988001
TI  - Gene V protein dimerization and cooperativity of binding of poly(dA).
AB  - Gene V protein of bacteriophage f1 is a dimeric protein that binds cooperatively
      to single-stranded nucleic acids. In order to determine whether a monomer-dimer
      equilibrium has an appreciable effect upon the thermodynamics of gene V protein
      binding to nucleic acids, the dissociation constant for the protein dimer was
      investigated using size-exclusion chromatography. At concentrations ranging from
      5 x 10(-10) to 1.2 x 10(-5) M, the Stokes radius of the protein was that expected
      of the dimer of the gene V protein. The Stokes radius of the protein was also
      independent of salt concentration from 0.2 to 1.0 M NaCl in a buffer containing
      10 mM Tris-HCl, pH 7.4, and 1 mM EDTA. The binding of the dimeric gene V protein
      to poly(dA) was studied using a simplified lattice model for protein-protein
      interactions adapted for use with a dimeric protein that binds simultaneously to
      two strands of nucleic acid. Interpretation of the salt dependence, C = [d
      log(Kint omega)]/[d log(NaCl)], of binding of such a dimeric protein to nucleic
      acid using the theory of Record et al. (Record, M. T., et al. (1976) J. Mol.
      Biol. 107, 145-158) indicates that C is a function of the numbers of cations and
      anions released from protein and nucleic acid upon binding of the dimer, not of
      the monomer. Cooperativity of gene V protein binding to poly(dA) was studied with
      titration experiments that are sensitive to the degree of cooperativity of
      binding. The cooperativity factor omega, defined as the ratio of the binding
      constant for a site adjacent to a previously bound dimer to that for an isolated
      site, was found to be relatively insensitive to salt, with a value in the range
      of 2000-7000 for binding to poly(dA) at 3 degrees C and at 23 degrees C. This
      high cooperativity factor supports the suggestion that protein-protein contacts
      play a major role in the formation of the superhelical gene V protein-single
      stranded nucleic acid complex.

PMID- 8988002
TI  - Specific recognition of A/G and A/7,8-dihydro-8-oxoguanine (8-oxoG) mismatches by
      Escherichia coli MutY: removal of the C-terminal domain preferentially affects
      A/8-oxoG recognition.
AB  - Escherichia coli MutY is a 39 kDa adenine DNA glycosylase and 3'
      apurinic/apyrimidinic (AP) lyase that is active on DNA substrates containing A/G,
      A/C, or A/8-oxoG mismatches. 8-oxoG (7,8-dihydro-8-oxoguanine or GO) is a major
      stable product of oxidative damage, and A/GO mismatches may be particularly
      important biological substrates for MutY. Proteolytic digestion of MutY using
      thermolysin was found to produce two relatively stable fragments of 25 and 12
      kDa. The 25 kDa fragment begins at the N terminus of MutY and spans the region
      homologous with E. coli endonuclease III, a DNA glycosylase/AP lyase that repairs
      oxidatively damaged pyrimidines. The 12 kDa fragment, which consists of much of
      the rest of MutY, had no detectable activity. The purified 25 kDa fragment (M25)
      had nearly wild-type binding and cleavage activities with A/G-mismatched
      substrates. Binding to A/GO-mismatched DNA, however, was dramatically reduced in
      M25 compared to that in intact protein. Borohydride-dependent enzyme-DNA cross
      linking, which is a hallmark of the reaction of several DNA glycosylases that
      possess concomitant AP lyase activity, was also substantially reduced when M25
      was allowed to react with A/GO-mismatched DNA. The significant differences in M25
      recognition and reactivity with A/G and A/GO mismatches suggest that the C
      terminal region of MutY, a region with no homologous counterpart in E. coli
      endonuclease III, plays an important role in the repair of mismatched DNA arising
      from oxidation damage.

PMID- 8988003
TI  - Rotational and conformational dynamics of Escherichia coli ribosomal protein
      L7/L12.
AB  - Fluorescence methods were utilized to study dynamic aspects of the 24 kDa dimeric
      Escherichia coli ribosomal protein L7/L12. Oligonucleotide site-directed
      mutagenesis was used to introduce cysteine residues at specific locations along
      the peptide chain, in both the C-terminal and N-terminal domains, and various
      sulfhydryl reactive fluorescence probes (iodoacetamido) fluorescein, IAEDANS,
      pyrenemethyl iodoacetate) were attached to these residues. In addition to the
      full-length proteins, a hinge-deleted variant and variants corresponding to the C
      terminal fragment and the N-terminal fragment were also studied. Both steady
      state and time-resolved fluorescence measurements were carried out, and the
      results demonstrated that L7/L12 is not a rigid molecule. Specifically, the two C
      terminal domains move freely with respect to one another and with respect to the
      dimeric N-terminal domain. Removal of the hinge region, however, significantly
      reduces the mobility of the C-terminal domains. The data also show that the
      rotational relaxation time monitored by the fluorescent probe-depends upon the
      probe's excited state lifetime. This observation is interpreted to indicate that
      a hierarchy of motions exists in the L7/L12 molecule including facile motions of
      the C-terminal domains and dimeric N-terminal domain, in addition to the overall
      tumbling of the protein. Probes attached to the N-terminal domain exhibit global
      rotational relaxation times consistent with the molecular mass of the dimeric N
      terminal fragment. Upon reconstitution of labeled L7/L12 with ribosomal cores,
      however, the motion associated with the dimeric N-terminal domain is greatly
      diminished while the facile motion of the C-terminal domains is almost unchanged.

PMID- 8988004
TI  - Dimer/monomer equilibrium and domain separations of Escherichia coli ribosomal
      protein L7/L12.
AB  - The dimer to monomer equilibrium and interdomain separations of cysteine variants
      of L7/L12 have been investigated using fluorescence spectroscopy. Steady-state
      polarization measurements on cysteine containing variants of L7/L12, labeled with
      5-(iodoacetamido)fluorescein, demonstrated dimer to monomer dissociation
      constants near 30 nM for variants labeled at position 33, in the N-terminal
      domain, and positions 63 and 89, in the C-terminal domain. A dissociation
      constant near 300 nM was determined for a variant labeled at position 12, in the
      N-terminal domain. The polarization of a labeled C-terminal fragment did not
      change over the range of 200 microM to 1 nM, indicating that this construct
      remains monomeric at these concentrations, whereas a dimer to monomer
      dissociation constant near 300 nM was observed for an FITC labeled N-terminal
      fragment. Intersubunit fluorescence resonance energy self-transfer was observed
      when appropriate probes were attached to cysteines at residues 12 or 33, located
      in the N-terminal domain. Probes attached to cysteines at positions 63 or 89 in
      the C-terminal domain, however, did not exhibit intersubunit self-transfer. These
      results indicate that these residues in the C-terminal domains are, on average,
      separated by greater than 85 A. Intersubunit self-transfer does occur in a C-89
      double mutation variant lacking 11 residues in the putative hinge region,
      indicating that the loss of the hinge region brings the two C-terminal domains
      closer together. Rapid subunit exchange between unlabeled wild-type L7/L12 and
      L7/L12 variants labeled in the N-terminal domain was also demonstrated by the
      loss of self-transfer upon mixing of the two proteins.

PMID- 8988005
TI  - Fluorescence emission of ethidium bromide intercalated in defined DNA duplexes:
      evaluation of hydrodynamics components.
AB  - The arrangement and stacking of noncovalently contiguous double-helical sections
      are increasingly invoked in single-stranded DNA and RNA tertiary structure. These
      tertiary structures of nucleic acids are defined by their double stranded
      regions, and their orientation in the molecular frame constitutes an important
      component of the nucleic acid structure. A direct view of these tertiary
      structures can be obtained by fluorescence polarization anisotropy of bound
      ethidium bromide (EB). The orientation of the dye in the molecular frame of the
      nucleic acid yields the orientation of the helix. The complete anisotropy
      function for EB intercalated in genome-derived DNA duplexes was derived by
      Allison and Schurr (1979) and accounts for base-pair twisting and DNA bending.
      Single-stranded ribozymes, ribosomal and transfer RNAs, and model DNA junctions
      contain double-stranded regions shorter than 35 bp in length, for which bending
      is not significant. We developed and experimentally verified an expression of the
      anisotropy function for short DNA duplexes which is theoretically compatible with
      the existing theory, originally developed for long nucleic acids (Schurr et al.,
      1992). Simulations showed that for DNA duplexes shorter than 35 bp, our
      expression of the anisotropy function is equivalent to Schurr's and is consistent
      with experiments carried out on eight DNA duplexes. Modeling the eight duplexes
      as cylinders, we calculate a duplex diameter of 1.91 +/- 0.15 nm when EB makes a
      90 degrees angle with the DNA helix axis and undergoes anisotropic wobbling and
      1.97 +/- 0.15 nm when EB makes a 70.5 degrees angle and undergoes isotropic
      wobbling, respectively. We used this treatment to establish the conformation of
      five DNA oligonucleotides made of single and tethered hairpins, some designed to
      exhibit coaxial stacking. Analysis of the fluorescence anisotropy decays shows
      that the tethered hairpins take an extended rather than parallel conformation. It
      also shows that the DNA oligonucleotides made of two tethered hairpins exhibit
      freedom compatible with two independent hairpins. When the linker between
      hairpins is shortened, the two hairpins are not independent anymore as probed by
      fluorescence anisotropy, suggesting coaxial stacking of the two helices.

PMID- 8988006
TI  - NMR characterization of side chain flexibility and backbone structure in the type
      I antifreeze protein at near freezing temperatures.
AB  - The flexibility of the polar side chains in the alpha-helical Type I antifreeze
      protein (AFP) near the solution freezing temperature was investigated by two
      dimensional nuclear magnetic resonance spectroscopy. These experiments were
      conducted to define the rotameric conformations of the proposed ice-binding
      groups, threonines and asparagines, in order to probe the molecular mechanism for
      ice binding. On the basis of the 3J alpha beta 2 NMR coupling constant values of
      7.1, 8.5, 8.5, and 6.8 Hz for residues T2, T13, T24, and T35, respectively, it
      can be calculated that the regularly spaced ice-binding threonines sample many
      possible rotameric states prior to ice binding. The lack of a dominant side chain
      rotamer is further corroborated by nuclear Overhauser distance measurements for
      T13 and T24. N16 and N27, both with 3J alpha beta 2 and 3J alpha beta 3 coupling
      constants of 8.4 and 4.5 Hz, respectively, show a slight preference for the side
      chain conformation with a chi 1 of -60 degrees. These data suggest that prior to
      ice binding the threonine and asparagine side chains are free to rotate and that
      a unique preformed ice-binding structure in solution is not apparent. These
      observations do not support the rigid side chain model proposed recently by an X
      ray study [Sicheri, F., & Yang, D. S. C. (1995) Nature 375, 427-431].

PMID- 8988007
TI  - Site-specific d(GpG) intrastrand cross-links formed by dinuclear platinum
      complexes. Bending and NMR studies.
AB  - The novel platinum drugs [{trans-PtCl(NH3)2}2H2N(CH2)nNH2]2+ (1,1/t,t) are
      currently undergoing preclinical development. The bifunctional DNA binding of
      these agents allows comparison with that of cisplatin [Farrell et al. (1995)
      Biochemistry, 34, 15480]. The major DNA lesion of cisplatin, the 1,2-d(GpG)
      intrastrand adduct, produces a rigid, directed bend 30-35 degrees into the major
      groove of DNA. We have now completed a structural analysis of the corresponding
      adduct formed with the dinuclear complexes. Gel retardation assays on 15-22 bp
      oligonucleotides containing a central d(TG*G*T) site show that the (Pt,Pt)
      intrastrand adducts result in a flexible nondirectional bend. This bend is
      essentially independent of chain length (n = 2, 4, 6). Chemical reactivity assays
      indicated a hypersensitivity of the thymine 5' to the adduct and an enhanced
      sensitivity of the 3'-thymine to OsO4. 2D 1H NMR studies on a d(TG1G2T) adduct of
      [{trans-PtCl(NH3)2}2H2N(CH2)6NH2]2+ have delineated the structural features
      responsible for these observations. In contrast to the cisplatin adduct, which
      displays a 100% N-type sugar of the 5'-G and an anti base conformation of the
      platinated bases in both solid state and solution, the dinuclear adduct does not
      display the typical N-type sugar pucker. The base orientations are anti (5'-T),
      anti (G1), anti/syn (G2), and anti (3'-T) while the sugar conformations are N,
      S/N, N, and S, respectively. The 5'-T remains stacked with its guanine neighbor
      while the 3'-T becomes unstacked, a reverse of the situation observed for cis
      DDP.

PMID- 8988008
TI  - DNA-induced lateral segregation of cationic amphiphiles in lipid bilayer
      membranes as detected via 2H NMR.
AB  - 2H NMR spectroscopy was used to investigate the response of specifically choline
      deuterated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) to changes in
      surface electrostatic charge in membranes consisting of mixtures of POPC plus
      various cationic amphiphiles plus polyadenylic acid (polyA). Three different
      cationic amphiphiles were investigated: cetyltrimethylammonium bromide (CTAB),
      dioleoyldimethylaminopropane (DODAP), and 3 beta [N-(N',N'
      dimethylaminoethane)carbamoyl]-cholesterol (DC-CHOL). Each of the cationic
      amphiphiles elicited a concentration-dependent decrease (increase) in the
      quadrupolar splitting from POPC-alpha-d2 (POPC-beta-d2), as expected for the
      accumulation of cationic charges at the surface of a lipid bilayer. However, the
      strength of the response varied with the cationic amphiphile in the order CTAB >
      DODAP > DC-CHOL. When polyA was added to the cationic amphiphile-containing lipid
      bilayers, the 2H NMR spectrum consisted of two overlapping Pake patterns,
      indicating the presence of two lipid domains with different effective surface
      charges and only slow exchange of lipids between the two domains. There was no
      evidence of any non-bilayer lipid arrangements. Analysis of the quadrupolar
      splittings of the two 2H NMR spectral components demonstrated that the polyA
      containing domain was enriched with respect to cationic amphiphiles while the
      polyA-free domain was depleted with respect to cationic amphiphiles. We conclude
      that polyA is able to laterally segregate cationic amphiphiles into long-lived
      lipid domains of distinct composition.

PMID- 8988009
TI  - Molecular recognition by cholesterol esterase of active site ligands: structure
      reactivity effects for inhibition by aryl carbamates and subsequent
      carbamylenzyme turnover.
AB  - Interactions of mammalian pancreatic cholesterol esterases from pig and rat with
      a family of aryl carbamates CnH2n+1NHCOOAr [n = 4-9; Ar = phenyl, p-X-phenyl (X =
      acetamido, bromo, fluoro, nitro, trifluoromethyl), 2-naphthyl, 2
      tetrahydronaphthyl, estronyl] have been investigated, with an aim of delineating
      the ligand structural features which lead to effective molecular recognition by
      the active site of the enzyme. These carbamates inhibit the catalytic activity of
      CEase by rapid carbamylation of the active site, a process that shows saturation
      kinetics. Subsequent slow decarbamylation usually leads to full restoration of
      activity, and therefore aryl carbamates are transient inhibitors, or pseudo
      substrates, of CEase. Structural variation of carbamate inhibitors allowed
      molecular recognition in the fatty acid binding and steroid binding loci of the
      extended active site to be probed, and the electronic nature of the carbamylation
      transition state to be characterized. Optimal inhibitory activity is observed
      when the length of the carbamyl function is n = 6 and n = 7 for porcine and rat
      cholesterol esterases, respectively, equivalent to eight- and nine-carbon fatty
      acyl chains. In contrast, inhibitory activity increases progressively as the
      partial molecular volume of the aromatic fragment increases. Hammett plots for p
      substituted phenyl-N-hexyl carbamates indicate that the rate-determining step for
      carbamate inhibition is phenolate anion expulsion. Effects of the bile salt
      activator taurocholate on the kinetically resolved phases of the pseudo-substrate
      turnover of aryl carbamates were also studied. Taurocholate increases the
      affinity of the carbamate for the active site of cholesterol esterase in the
      reversible, noncovalent complex that precedes carbamylation and increases the
      rate constants of the serial carbamylation and decarbamylation steps. Structural
      variation of the N-alkyl chain and of the aryl fused-ring system provides an
      accounting of bile salt modulation of the fatty acid and steroid binding sites,
      respectively. In that pseudo-substrate turnover of aryl carbamates proceeds by a
      three-step mechanism that is analogous to that for rapid turnover of lipid ester
      substrates, these investigations illuminate details of ligand recognition by the
      extended active site of cholesterol esterase that are prominent determinants of
      the substrate specificity and catalytic power of the enzyme.

PMID- 8988010
TI  - Tetrahydrobiopterin-free neuronal nitric oxide synthase: evidence for two
      identical highly anticooperative pteridine binding sites.
AB  - The properties of neuronal nitric oxide synthase containing one
      tetrahydrobiopterin (BH4) per dimer [nNOS(BH4+)] were compared to those of the
      BH4-free enzyme [nNOS(BH4-)]. The stimulation by BH4 of the formation of L
      citrulline at the expense of H2O2 production unambiguously demonstrated that BH4
      is essential in coupling reductive oxygen activation to Arg oxidation. The clear
      difference between the Stokes radii of nNOS(BH4-) and nNOS(BH4+) indicates that
      the introduction of one BH4 per dimer significantly changes the enzyme structure.
      Whereas the heme in nNOS(BH4+) was primarily high-spin, nNOS(BH4-) contained
      mainly low-spin heme. This was slowly converted into the high-spin form with Arg
      and/or BH4, with a rate that was independent of the concentration of either
      compound. Dithiothreitol inhibited the Arg/BH4-induced spin conversion by
      stabilizing low-spin heme. Formation of high-spin heme, with rates varying from
      0.04 to 0.4 min-1, always correlated to an equally fast increase in activity.
      Radioligand binding studies showed the rapid association (within 20 s) of BH4 to
      nNOS(BH4-), but not to nNOS(BH4+), after preincubation with Arg. Complete and
      monophasic dissociation of radioligand occurred in the presence of excess
      unlabeled BH4, demonstrating the exchangeability of high-affinity bound BH4.
      Studies of the association of NG-nitro-L-arginine (L-NNA) to nNOS(BH4+) revealed
      that excess BH4 increased the amount of bound L-NNA 2-fold. Most of the binding
      data are explained by a model in which nNOS dimers accommodate two identical BH4-
      and Arg/L-NNA-binding sites, with cooperativity between Arg- and BH4-binding and
      anticooperativity between the BH4-binding sites.

PMID- 8988011
TI  - Determination of affinities for lck SH2 binding peptides using a sensitive
      fluorescence assay: comparison between the pYEEIP and pYQPQP consensus sequences
      reveals context-dependent binding specificity.
AB  - The development of a sensitive fluorescence binding assay for evaluating the
      binding of phosphotyrosyl (pY) peptides to the recombinant SH2 domain of lck in
      solution is described. Several fluorescent peptides containing the consensus
      sequence of the viral hamster polyoma middle T antigen (pYEEI) were
      characterized. The peptides contained either the acetamido-anilino-naphthyl
      sulfonic acid (AANS), acrylodan, or dansyl groups as fluorophores. The spectral
      features of these probes were characterized in the presence and absence of the
      lck SH2 domain. The binding affinities (Kd) for the fluorescent peptides studied
      ranged from 40 to 500 nM. The fluorescent peptide containing the sequence
      FTATEC(AANS)QpYEEIP exhibited the highest binding affinity (Kd = 3.98 x 10(-8) M)
      and largest change in emission intensity (approximately 8.7-fold) upon binding
      the SH2 domain. This probe was subsequently used in competitive binding assays to
      study the interaction of the lck SH2 domain with a series of phosphopeptides
      related to the pYEEIP and pYQPQP (the pY505 C-terminal) consensus sequences. The
      effects of peptide length and substitutions of residues within the pYEEIP
      sequence are discussed in terms of binding affinities. Comparison between the two
      peptide series revealed that the contributions of individual substitutions to
      binding affinity are context-dependent. The data also led to the conclusion that
      the presence of P at +2 results in a functional "truncation" of the binding
      sequence; i.e., residues at positions higher than +2 do not participate
      significantly in binding. This implicit truncation may actually be a desired
      property for the autoregulatory nature of the pYQPQP sequence, since it retains
      specificity for the SH2 domain while adjusting the Kd to a value appropriate for
      maintaining the delicate balance of receptor-ligand interactions that are
      involved in signal transduction events.

PMID- 8988012
TI  - Thermodynamic characterization of the partially unfolded state of Ca(2+)-loaded
      bovine alpha-lactalbumin: evidence that partial unfolding can precede Ca2+
      release.
AB  - The thermal denaturation of bovine alpha-lactalbumin (BLA) was studied at pH 7.5
      and at various Ca2+ concentrations using near-UV circular dichroism and
      differential scanning calorimetry. The Ca2+ dependence of the denaturation
      equilibria proves that, in the transition region, partially unfolded alpha
      lactalbumin consists of a mixture of Ca(2+)-loaded and Ca(2+)-free protein. The
      thermodynamic parameters of the unfolding of these two species were determined at
      68 degrees C and were then compared with one other, with the thermodynamic
      parameters deduced from calorimetric titration of alpha-lactalbumin with Ca2+,
      and with those derived from Ca2+ titration of a mutant human lysozyme having an
      engineered Ca(2+)-binding site. This comparison indicated that (a) the unfolding
      curves for Ca(2+)-BLA deduced from the near-UV ellipticity change are more able
      to distinguish between unfolding with and without Ca2+ release than those deduced
      from differential scanning calorimetry, (b) the Ca(2+)-loaded denaturated state
      of BLA is more folded than the Ca(2+)-free protein at 68 degrees C, and (c) a
      heat-induced unfolding process, consisting of an initial Ca2+ release, followed
      by a conformational relaxation, is unlikely to occur at the experimental pH and
      in the millimolar region of Ca2+ concentrations, due to the large free energy
      requirement of the initial step. A more probable mechanism would be unfolding via
      a Ca(2+)-loaded intermediately unfolded state, with subsequent Ca2+ release.

PMID- 8988014
TI  - Electron transfer from the nitrogenase iron protein to the [8Fe-(7/8)S] clusters
      of the molybdenum-iron protein.
AB  - The reduction of substrates catalyzed by nitrogenase requires electron transfer
      between the iron (Fe) protein and the molybdenum-iron (MoFe) protein in a
      reaction that is coupled to the hydrolysis of MgATP. The [4Fe-4S] cluster of the
      Fe protein transfers one electron ultimately to the M-clusters (FeMoco) of the
      MoFe protein for substrate reduction, with the P-clusters ([8Fe-(7/8)S]) of the
      MoFe protein as proposed electron transfer intermediates. This work presents
      direct EPR evidence for primary electron transfer from the [4Fe-4S] cluster of
      the Fe protein to the P-clusters of the MoFe protein in a reaction that requires
      the MgATP-bound state of the Fe protein. An oxidized state of the MoFe protein
      was prepared in which the P-clusters were oxidized by 2 equiv of electrons to the
      P2+ state. In this oxidation state, the M-clusters (S = 3/2) and the P(2+
      clusters (S > or = 3) are paramagnetic and can be observed by perpendicular and
      parallel mode EPR, providing the opportunity to follow electron transfer from the
      Fe protein to either cluster type in the MoFe protein. Electron transfer from the
      reduced [4Fe-4S]1+ cluster of two different Fe proteins to the P2+ clusters of
      the MoFe protein was observed by the disappearance of the [4Fe-4S]1+ cluster EPR
      signal and the conversion of the MoFe protein P-clusters from the P2+ to the P1+
      oxidation state. In the first case, stoichiometric quantities of the wild-type Fe
      protein transferred one electron to the P-clusters only in the presence of MgATP.
      MgADP would not support this electron transfer reaction. In the second case, an
      altered Fe protein (L127 delta) that is in a conformation resembling the MgATP
      bound state was found to transfer an electron to the P-clusters in the absence of
      MgATP. These results suggest that the first electron transferred from the Fe
      protein goes to the P-cluster and that the MgATP-bound protein conformation of
      the Fe protein, not MgATP hydrolysis, is required for this electron transfer
      reaction.

PMID- 8988015
TI  - Resonance Raman evidence that photodissociation of nitric oxide from the non-heme
      iron center activates nitrile hydratase from Rhodococcus sp. N-771.
AB  - Nitrile hydratase (NHase) from Rhodococcus sp. N-771, which contains a non-heme
      iron center in the catalytic site, has been known to be activated by light
      illumination. Recently, endogenous nitric oxide (NO) was found in this enzyme by
      FTIR spectroscopy [Noguchi et al. (1995) FEBS Lett. 358, 9-12]. In order to
      directly detect the bonding between NO and the iron atom and the reaction of NO
      upon photoactivation, resonance Raman spectra of the NHase were measured with 413
      nm excitation at 85 K. Two prominent bands at 592 and 570 cm-1 were observed in
      the inactive from, and both of them were completely lost upon photoactivation.
      Upon subsequent introduction of 15NO, the active NHase was converted to the
      inactive form again and the above two bands were restored with downshifts by 10
      and 12 cm-1, respectively. Also, the excitation profiles of these bands in the
      350-500 nm region mostly followed the absorption spectrum arising from the iron
      center. From these isotopic shifts and the excitation profiles, the two Raman
      bands were assigned to the Fe-NO stretching and bending vibrations that are
      probably coupled with each other. The results provided solid evidence that NO is
      bound to the non-heme iron in the inactive NHase and its photodissociation
      activates the enzyme.

PMID- 8988013
TI  - Endoplasmic reticulum chaperone GRP94 subunit assembly is regulated through a
      defined oligomerization domain.
AB  - GRP94 is an abundant, resident glycoprotein of the mammalian endoplasmic
      reticulum lumen and member of the hsp90 family of molecular chaperones. To
      identify the structure/function relationships which define the molecular basis of
      GRP94 activity, we have performed a structural analysis of native GRP94 and
      identified a discrete domain, representing amino acids 676-719, which regulates
      dimerization and displays autonomous oligomerization activity. Velocity
      sedimentation and gel filtration chromatography were used to identify native
      GRP94 as a dimer with an extended, rod-like shape. Limited proteolysis resulted
      in the loss of approximately 16 kDa from the C-terminus and disassembly into
      monomers, implicating the C-terminus as the site of assembly. An assembly
      function for the C-terminal domain was established by analysis of the quaternary
      structure of C-terminal constructs synthesized either in vitro or through
      recombinant expression. In vitro translation was used to demonstrate that a C
      terminal 20 kDa domain was both necessary and sufficient for dimerization.
      Structural studies of recombinant fusion protein constructs yielded
      identification of a 44 amino acid domain that displayed autonomous dimerization
      activity and conferred a highly elongated structure, characteristic of native
      GRP94, to the fusion protein. These data, combined with molecular dimensions
      obtained from rotary shadowing electron microscopy, provide a structural model of
      GRP94 and identify the molecular basis of GRP94 self-assembly.

PMID- 8988016
TI  - FTIR study of conformational substates in the CO adduct of cytochrome c oxidase
      from Rhodobacter sphaeroides.
AB  - Fourier transform infrared (FTIR) spectroscopy of cytochrome c oxidase from
      Rhodobacter sphaeroides reveals multiple CO stretch bands that are associated
      with different conformational substates of the enzyme. Here we report the
      temperature dependence of the infrared bands for the CO bound to the Fea3 heme
      iron and to CuB. We have also studied the kinetics of ligand return from Fea3 to
      CuB using temperature derivative spectroscopy (TDS). Two classes of substates
      (alpha/beta) can be distinguished from their different properties with regard to
      the width of the IR band, the temperature dependence of the peak position, and
      the peak of the enthalpy distribution. The pronounced temperature dependence of
      the stretch frequencies in the beta conformation and the lack thereof in the
      alpha conformation implies very different dynamic behavior in the active site and
      reflects structural differences between the two conformations, most likely a
      shift of the position of CuB in response to a change in its stereochemical
      environment. Similar conformational changes will be necessary during the
      catalytic cycle of the enzyme when dioxygen is bound in the active site.

PMID- 8988017
TI  - Differential scanning calorimetric study of the interaction of cholesterol with
      the major lipids of the Acholeplasma laidlawii B membrane.
AB  - It has been proposed that the lower levels of exogenous cholesterol incorporation
      into the membranes of the sterol-non-requiring as compared to the sterol
      requiring mycoplasmas may be due to the much higher glycolipid content of the
      former and to the reduced ability of glycolipids, as opposed to phospholipids, to
      incorporate sterols [Efrati et al. (1986) Arch. Biochem. Biophys. 248, 282-288].
      In order to test this hypothesis, we have investigated the interaction of
      cholesterol with the major membrane glyco- and phospholipids of the sterol-non
      requiring mycoplasma Acholeplasma laidlawii B, utilizing elaidic acid-homogenous
      membranes in order to obviate any differences in the nature of cholesterol-lipid
      interactions due to variations in the fatty acid composition of the different
      membrane components. Specifically, we have studied the effect of increasing
      quantities of cholesterol on the thermotropic phase behavior of aqueous
      dispersions of phosphatidylglycerol, diglucosyl diacylglycerol, and monoglucosyl
      diacylglycerol, as well as the total membrane polar lipids of this organism,
      using high-sensitivity differential scanning calorimetry. We find that
      cholesterol is highly miscible in both the lamellar gel and liquid-crystalline
      states of phosphatidylglycerol but exhibits limited miscibility in the two
      neutral glycolipids, particularly in their lamellar gel and crystalline states.
      We also demonstrate that cholesterol has a limited miscibility in both the
      lamellar gel and liquid-crystalline states of bilayers composed of the total A.
      laidlawii B membrane polar lipids. These results demonstrate that the nature of
      cholesterol-lipid interactions depends markedly on the structure of the
      glycerolipid polar headgroup and suggests that the incorporation of lower levels
      of cholesterol into the membranes of the sterol-non-requiring mycoplasmas may
      indeed be due, at least in part, to their high glycolipid contents. We also show
      that cholesterol stabilizes the lamellar liquid-crystalline phase of the
      monoglucosyl diacylglycerol relative to the inverted hexagonal phase at all
      sterol concentrations, in contrast to the effects of cholesterol on
      dielaidoylphosphatidylethanolamine, which destabilizes the lamellar liquid
      crystalline phase at low concentrations.

PMID- 8988018
TI  - Glial cell line-derived neurotrophic factor: selective reduction of the
      intermolecular disulfide linkage and characterization of its disulfide structure.
AB  - Glial cell line-derived neurotrophic factor is a protein known to enhance the
      survival of dopaminergic neurons against several neurotoxins. It has been shown
      to have therapeutic potential in the treatment of Parkinson's disease and other
      neurodegenerative diseases. We have determined the inter- and intramolecular
      disulfide linkages of the dimeric molecule by a combination of direct peptide
      analysis and peptide analysis after either partial reduction or partial oxidation
      of the protein. Under an acidic condition, the interchain disulfide bond was
      selectively cleaved with tris(2-carboxyethyl)phosphine, revealing that Cys101 was
      involved in the intermolecular disulfide linkage. Three other disulfides, Cys68
      Cys131, Cys72-Cys133, and Cys41-Cys102, were identified as intramolecular
      linkages. The determined disulfide structure is highly homologous to that of
      transforming growth factor beta 2. Since one intramolecular disulfide points
      through a ring consisting of eight amino acid residues based on the similarity
      with transforming growth factor beta 2, the disulfide-linked peptides were not
      purified by conventional methods. Only the peptides from an N-terminal region
      (residues -1 to 37) were liberated by proteolytic treatment with trypsin or
      endoproteinase Lys-C, resulting in a stable cystine-knot protein.

PMID- 8988019
TI  - Chloride channel properties of the uncoupling protein from brown adipose tissue
      mitochondria: a patch-clamp study.
AB  - The uncoupling protein (UCP) from brown adipose tissue mitochondria possesses H+
      and Cl- transport activities [reviewed in Klingenberg, M. (1990) Trends Biochem.
      Sci. 15, 108-112]. Being a member of a mitochondrial carrier family, the
      transport of H+ and Cl- is carrier-like, i.e., much slower as compared to
      channels. Here we report that UCP reconstituted into giant liposomes displays
      stable chloride channel properties under patch-clamp conditions. The transport
      inhibitors (GTP, GDP, ATP, and ADP) also inhibit this channel in a reversible
      way, showing that the channel activity is associated with UCP. The slightly
      inward-rectifying chloride channel has a unit conductance of approximately 75 pS
      in symmetrical 100 mM KCl and closes at high positive potentials on the matrix
      side of UCP. Channel gatings switch from slow open-closure transitions to fast
      flickerings as the holding potential increases over +60 mV. Substitution
      experiments reveal a strong discrimination against cations [P(Cl-)/P(K+)
      approximately 17] and a permeability ratio order of Cl- > Br- > F- > SCN- > I- >
      NO3- > SO4(2-) > HPO4(2-) > gluconate. Nucleotide inhibition studies indicate
      that 70% UCP molecules had its matrix side oriented outside in the giant
      liposomes. Fatty acids, pH, divalent cations (Ca2+ and Mg2+), and mersalyl do not
      influence these Cl- currents. The Cl- channel can be blocked by 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) from the matrix side of UCP.
      The data are consistent with a dimer consisting of two monomeric 75-pS Cl-
      channels or with a monomeric 150-pS channel having a 50% subconductance state.
      The channel current increases with Cl- concentration showing a typical saturation
      curve with Km approximately 63 mM and gmax approximately 120 pS (100 mM KCl in
      the pipet). The Cl- conductance measured under these conditions is 6 orders of
      magnitude higher than the Cl- transport activity reported earlier, suggesting
      that the UCP has the potential of behaving as an anion channel.

PMID- 8988020
TI  - Identification of competitive antagonists of the rod photoreceptor cGMP-gated
      cation channel: beta-phenyl-1,N2-etheno-substituted cGMP analogues as probes of
      the cGMP-binding site.
AB  - cGMP is the natural activator of the cyclic nucleotide-gated channel originally
      isolated from rod photoreceptors but now known to be expressed in a wide variety
      of neural and non-neural cells. To identify antagonists of cGMP action and to
      better understand the interaction between cGMP and the channel protein,
      experimental studies were undertaken using four synthetic cGMP analogues, PET
      cGMP, 8-Br-PET-cGMP, Rp-8-Br-PET-cGMPS, and Sp-8-Br-PET-cGMPS. With excised
      patches from either Xenopus oocytes expressing a cloned rat rod channel alpha
      subunit or from native Xenopus rod photoreceptors, Rp-8-Br-PET-cGMPS
      competitively suppressed the cGMP-induced current with an IC50 of 25 microM and
      Sp-8-Br-PET-cGMPS inhibited this current with an IC50 of 105 microM. On the
      expressed rat rod channel, 8-Br-PET-cGMP behaved as a very weak partial agonist
      at high concentrations and an antagonist (IC50 = 64 microM) at lower
      concentrations when coapplied with cGMP. PET-cGMP did not activate channel
      currents alone but showed a synergism when coapplied with subsaturating
      concentrations of cGMP. Because Sp-8-Br-PET-cGMPS is a potent activator of type I
      cGMP-dependent protein kinase, but a competitive antagonist of channel
      activation, it will be a useful reagent for discriminating between those effects
      of cGMP that are mediated by a protein kinase and those mediated by channel
      activation. Because the PET derivatives all contain a phenyl-substituted 5
      membered ring system fused to the amino group in position 2 and the nitrogen in
      position 1 of the guanine ring, the results support the idea that N1 and N2 are
      important for channel activation. They also suggest a minor role for the cyclic
      phosphate group in binding or activation.

PMID- 8988021
TI  - Membrane binding of phospholipases C-beta 1 and C-beta 2 is independent of
      phosphatidylinositol 4,5-bisphosphate and the alpha and beta gamma subunits of G
      proteins.
AB  - We have measured the membrane binding affinities of purified phosphatidylinositol
      specific phospholipases C-beta 1 and C-beta 2 to membranes of varying lipid
      composition using fluorescence methods. Our studies show that these proteins bind
      with affinities of 10(-5)-10(-4) M, with a small dependence on lipid type.
      Binding was relatively insensitive to the presence of phosphatidylinositol
      specific phospholipases C-beta s' major physiological substrate,
      phosphatidylinositiol 4,5-bisphosphate, as well as the presence of Ca2+, which is
      required for activity. The presence of purified GTP gamma S-activated alpha 11
      subunits of heterotrimeric guanine nucleotide binding proteins (G proteins) did
      not alter the membrane binding affinity of phosphatidylinositol-specific
      phospholipases C-beta 1, even though alpha 11 is a potent activator of this
      protein. Similarly, the presence of purified beta gamma subunits of G proteins
      did not alter the membrane association of phosphatidylinositol-specific
      phospholipases C-beta 2 even though these subunits strongly activate this
      isoform. These results argue against a recruitment model for PLC-beta activation
      by G proteins, negatively charged lipids, Ca2+, or substrate, and suggest that
      activation occurs through association of the membrane-bound species.

PMID- 8988022
TI  - Thermodynamic properties of an extremely rapid protein folding reaction.
AB  - The cold-shock protein CspB from Bacillus subtilis is a very small beta-barrel
      protein, which folds with a time constant of 1 ms (at 25 degrees C) in a U
      reversible N two-state reaction. To elucidate the energetics of this extremely
      fast reaction we investigated the folding kinetics of CspB as a function of both
      temperature and denaturant concentration between 2 and 45 degrees C and between 1
      and 8 M urea. Under all these conditions unfolding and refolding were reversible
      monoexponential reactions. By using transition state theory, data from 327
      kinetic curves were jointly analyzed to determine the thermodynamic activation
      parameters delta H H2O++, delta S H2O++, delta G H2O++, and delta C p H2O++ for
      unfolding and refolding and their dependences on the urea concentration. 90% of
      the total change in heat capacity and 96% of the change in the m value (m = d
      delta G/d[urea]) occur between the unfolded state and the activated state. This
      suggests that for CspB the activated state of folding is unusually well
      structured and almost equivalent to the native protein in its interactions with
      the solvent. As a consequence of this native-like activated state a strong
      temperature-dependent enthalpy/entropy compensation is observed for the refolding
      kinetics, and the barrier to refolding shifts from being largely enthalpic at low
      temperature to largely entropic at high temperature. This shift originates not
      from the changes in the folding protein chains itself, but from the changes in
      the protein-solvent interactions. We speculate that the absence of intermediates
      and the native-like activated state in the folding of CspB are correlated with
      the small size and the structural type of this protein. The stabilization of a
      small beta-sheet as in CspB requires extensive non-local interactions, and
      therefore incomplete sheets are unstable. As a consequence, the critical
      activated state is reached only very late in folding. The instability of
      partially folded structure is a means to avoid misfolding prior to the rate
      limiting step, and a native-like activated state reduces the risk of non
      productive side reactions during the final steps to the native state.

PMID- 8988023
TI  - Real-time refolding studies of 6-19F-tryptophan labeled Escherichia coli
      dihydrofolate reductase using stopped-flow NMR spectroscopy.
AB  - Escherichia coli dihydrofolate reductase (ecDHFR, EC1.5.1.3) contains 5
      tryptophan residues that have been replaced with 6-19F-tryptophan. Five native
      and four of the five unfolded tryptophan resonances can be resolved in the 1D 19F
      NMR spectra and have been assigned [Hoeltzli, S. D., & Frieden, C. (1994)
      Biochemistry 33, 5502-5509]. This resolution allows the behavior of the native
      and the unfolded resonances assigned to each individual tryptophan to be
      monitored during the unfolding or refolding process. We now use these assignments
      and stopped-flow NMR to investigate the real-time behavior of specific regions of
      the protein during refolding of DHFR after dilution from 4.6 to 2.3 M urea
      (midpoint of the transition = 3.8 M) at 5 degrees C. Approximately half of the
      intensity of each of the four unfolded resonances is present at the first
      measurable time point (1.5 s). Little native resonance intensity is detectable at
      this time. The remaining unfolded resonance intensities present then disappear in
      two phases, with rates similar to the two slowest phases observed by either
      stopped-flow fluorescence or circular dichroism spectroscopy upon refolding under
      the same conditions. Substantial total resonance intensity is missing during the
      first 20 s of the refolding process. The appearance of the majority of native
      resonance intensity (as assessed by the height of each of the five native
      tryptophan resonances) is slow and similar for all five tryptophans. In contrast,
      the largest amplitude changes observed by either stopped-flow far-UV circular
      dichroism spectroscopy or fluorescence spectroscopy, and the greatest loss of
      unfolded resonance intensity, occur much more rapidly. We conclude from these
      studies: (1) that, under these conditions, the unfolded state remains
      substantially populated after initiation of refolding; (2) that the early steps
      in refolding involve a solvent protected intermediate containing substantial
      secondary structure, but (3) that the stable native side chain interactions form
      slowly and are associated with the final rate-limiting phase of the refolding
      process. Preliminary analysis of the area of broadened native resonances suggests
      that these resonances may appear at different rates, indicating that some regions
      of the protein begin to sample a native-like side chain environment while side
      chain environment in other regions of the protein remains less ordered. The
      results of this study are consistent with the earlier studies demonstrating that
      mobility of side chains is an early step in unfolding [Hoeltzli, S. D., &
      Frieden, C. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 9318-9322] and that recovery
      of enzymatic activity occurs as a late step in the folding process [Frieden, C.
      (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4413-4416].

PMID- 8988024
TI  - Kinetic mechanism of folding and unfolding of Rhodobacter capsulatus cytochrome
      c2.
AB  - In spite of marginal sequence homology, cytochrome c2 from photosynthetic
      bacteria and the mitochondrial cytochromes c exhibit some striking structural
      similarities, including the tertiary arrangement of the three main helices. To
      compare the folding mechanisms for these two distantly related groups of
      proteins, equilibrium and kinetic measurements of the folding/unfolding reaction
      of cytochrome c2 from Rhodobacter capsulatus were performed as a function of
      guanidine hydrochloride (GuHCl) concentration in the absence and presence of a
      stabilizing salt, sodium sulfate. Quenching of the fluorescence of Trp67 by the
      heme was used as a conformational probe. Kinetic complexities due to non-native
      histidine ligation are avoided, since cytochrome c2 contains only one histidine,
      His17, which forms the axial heme ligand under native and denaturing conditions.
      Quantitative kinetic modeling showed that both equilibrium and kinetic results
      are consistent with a minimal four-state mechanism with two sequential
      intermediates. The observation of a large decrease in fluorescence during the 2
      ms dead-time of the stopped-flow measurement (burst phase) at low GuHCl
      concentration, followed by a sigmoidal recovery of the initial amplitude toward
      the unfolding transition region, is attributed to a well-populated compact
      folding intermediate in rapid exchange with unfolded molecules. A nearly
      denaturant-independent process at low GuHCl concentrations reflects the rate
      limiting conversion of a compact intermediate to the native state. At high GuHCl
      concentrations, a process with little denaturant dependence is attributed to the
      rate-limiting Met96-iron deligation process during unfolding, which is supported
      by the kinetics of imidazole binding. The strong GuHCl-dependence of folding and
      unfolding rates near the midpoint of the equilibrium transition is attributed to
      destabilization of each intermediate and their transition states in folding and
      unfolding. Addition of sodium sulfate shifts the rate profile to higher
      denaturant concentration, which can be understood in terms of the relative
      stabilizing effect of the salt on partially and fully folded states.

PMID- 8988025
TI  - Competitive interaction of component enzymes with the peripheral subunit-binding
      domain of the pyruvate dehydrogenase multienzyme complex of Bacillus
      stearothermophilus: kinetic analysis using surface plasmon resonance detection.
AB  - The interactions of the peripheral enzymes (E1, a pyruvate decarboxylase, and E3,
      dihydrolipoyl dehydrogenase) with the core component (E2, dihydrolipoyl
      acetyltransferase) of the pyruvate dehydrogenase (PDH) multienzyme complex of
      Bacillus stearothermophilus have been analyzed using a biosensor based on surface
      plasmon resonance detection. A recombinant di-domain (lipoyl domain plus
      peripheral subunit-binding domain) from E2 was attached to the biosensor chip by
      means of the pendant lipoyl group. The dissociation constant (Kd) for the complex
      between the peripheral subunit-binding domain and E3 (5.8 x 10(-10) M) was found
      to be almost twice that for the complex with E1 (3.24 x 10(-10) M). This was due
      to differences in the rate constants for dissociation (kdiss); these were 1.06 x
      10(-3) and 1.87 x 10(-3) s-1 for the complexes with E1 and E3, respectively,
      whereas the rate constants for association (kass) were identical (3.26 x 10(6) M
      1 s-1). Separate studies using non-denaturing polyacrylamide gel electrophoresis
      confirmed the difference in affinity and demonstrated that E1 can rapidly
      displace E3 from an E3-di-domain complex and vice versa. The peripheral subunit
      binding domain showed no detectable interaction with the E1 alpha subunit of E1
      (alpha 2 beta 2) but exhibited a strong affinity for E1 beta (Kd = 8.5 x 10(-9)
      M), confirming that the E1 beta subunit is responsible for binding E1 to E2.
      These measurements introduce new features of potential importance into the
      assembly and mechanism of the multienzyme complex.

PMID- 8988026
TI  - Yeast sterol C8-C7 isomerase: identification and characterization of a high
      affinity binding site for enzyme inhibitors.
AB  - The yeast gene ERG2 encodes a sterol C8-C7 isomerase and is essential for
      ergosterol synthesis and cell proliferation. Its striking homology with the so
      called sigma1 receptor of guinea pig brain, a polyvalent steroid and drug binding
      protein, suggested that the yeast sterol C8-C7 isomerase (ERG2) carries a similar
      high affinity drug binding domain. Indeed the sigma ligands [3H]haloperidol (Kd =
      0.3 nM) and [3H]ifenprodil (Kd = 1.4 nM) bound to a single population of sites in
      ERG2 wild type yeast microsomes (Bmax values of 77 and 61 pmol/mg of protein,
      respectively), whereas binding activity was absent in strains carrying ERG2 gene
      mutations or disruptions. [3H]Ifenprodil binding was inhibited by sterol
      isomerase inhibitors such as fenpropimorph (Ki = 0.05 nM), tridemorph (Ki = 0.09
      nM), MDL28,815 (Ki = 0.44 nM), triparanol (Ki = 1.5 nM), and AY-9944 (Ki = 5.8
      nM). [3H]Haloperidol specifically photoaffinity-labeled a protein with an
      apparent molecular weight of 27400, in agreement with the molecular mass of the
      sterol C8-C7 isomerase (24900 Da). 9E10 c-myc antibodies specifically
      immunoprecipitated the c-myc tagged protein after [3H]haloperidol photolabeling,
      unequivocally proving that the drug binding site is localized on the ERG2 gene
      product. Haloperidol, trifluperidol, and ifenprodil inhibited the growth of
      Saccharomyces cerevisiae and reduced the ergosterol content of cells grown in
      their presence. Our results demonstrate that the yeast sterol C8-C7 isomerase has
      a polyvalent high-affinity drug binding site similar to mammalian sigma receptors
      and that in yeast sigma ligands inhibit sterol biosynthesis.

PMID- 8988027
TI  - Mutation of lysines in a plasminogen binding region of streptokinase identifies
      residues important for generating a functional activator complex.
AB  - Through a unique but poorly understood mechanism, streptokinase (SK) interacts
      with human plasminogen to generate an "activator complex" that efficiently
      cleaves substrate plasminogen molecules. Previous studies have suggested that
      lysine residues in SK may play a role in the binding and function of the
      activator complex. To investigate this hypothesis, 10 different lysine residues
      in the plasminogen binding region of SK were altered to construct 8 recombinant
      (r) SK mutants. Only one double mutant, rSKK256,257A (replacing Lys with Ala at
      residues 256 and 257), showed a statistically significant reduction (63%) in
      binding affinity for Glu-plasminogen. This mutant also displayed a lagtime in the
      appearance of maximal activity, and modest impairments (2-5-fold) in kinetic
      parameters for amidolytic and plasminogen activator activity compared to rSK. In
      contrast, another mutant, rSKK332,334A, formed an activator complex with profound
      and nearly selective defects in the catalytic processing of substrate plasminogen
      molecules. When compared to rSK in kinetic assays of plasminogen activation, the
      rSKK332,334A mutant formed an activator complex that bound substrate plasminogens
      normally (normal K(m), but its ability to activate or cleave these molecules
      (kcat) was reduced by 34-fold. In contrast, in amidolytic assays, the kinetic
      parameters of rSKK332,334A showed only minor differences (< 2-fold) from rSK.
      Similarly, the binding affinity of this mutant to human Glu-plasminogen was
      indistinguishable from rSK [(2.6 +/- 0.8) x 10(9) vs (2.4 +/- 0.2) x 10(9) M-1,
      respectively]. In summary, these experiments have identified lysine residues in a
      plasminogen binding region of SK which appear to be necessary for normal high
      affinity binding to plasminogen, and for the efficient catalytic processing of
      substrate plasminogen molecules by the activator complex.

PMID- 8988028
TI  - Annexin V inhibition of factor IXa-catalyzed factor X activation on human
      platelets and on negatively-charged phospholipid vesicles.
AB  - Annexin V was found to inhibit factor IXa-catalyzed factor X activation on both
      thrombin-activated human platelets and artificial lipid vesicles containing
      phosphatidylserine, supporting previous observations of the importance of
      negatively-charged lipid in potentiating the reaction. Annexin V reduced the Vmax
      of factor X activation in factor IXa titrations on the platelet surface with an
      IC50 of 4 nM in the absence of thrombin-activated factor VIII (factor VIIIa), and
      4.5 nM in its presence, whereas there was no effect on the EC50,FIXa. This
      noncompetitive inhibition is consistent with interference of recognition of the
      factor IXa binding site on the platelet, which was confirmed by equilibrium
      binding of [125I]-factor IXa to thrombin-activated platelets where, in the
      absence of factor VIIIa and factor X, annexin V reduced the number of factor IXa
      binding sites/platelet from 610 to 320, without changing the Kd,app. In the
      presence of factor VIIIa and factor X, annexin V reduced the number of binding
      sites, but also raised the Kd,app. Although factor VIIIa improved the affinity of
      factor IXa for the lipid surface from Kd approximately 60 nM in its absence to Kd
      1 nM in its presence, addition of annexin V to factor IXa titrations on lipid
      vesicles in the presence of factor VIIIa increased the EC50,FIXa with an IC50 of
      1.5 nM, without affecting the Vmax. These data provide evidence that factor IXa,
      although requiring negatively-charged phospholipid for part of its binding site,
      is accommodated differently on platelets and on artificial vesicles.

PMID- 8988029
TI  - Identification of a novel region of homozygous deletion on chromosome 9p in
      squamous cell carcinoma of the lung: the location of a putative tumor suppressor
      gene.
AB  - Cytogenetic and molecular studies have implied the presence of tumor suppressor
      genes (TSGs) on chromosome 9p that are critical in the development of lung and
      other cancers. The p16/CDKN2 gene, a cyclin dependent kinase inhibitor, is a well
      defined TSG on 9p21. Although the frequency of mutations in the p16/CDKN2 gene
      has been detected in approximately 30% of non-small cell lung cancer, loss of
      heterozygosity on 9p has been observed in greater than 70% of non-small cell lung
      cancers. These and other deletion mapping studies have suggested the existence of
      additional TSGs on 9p. This study examined chromosome 9p for TSG loci by
      analyzing 23 squamous cell carcinomas of the lung with 21 microsatellite markers.
      Loss of heterozygosity was detected in all of the tumors, and homozygous
      deletions of the p16/ CDKN2 locus were observed in 6 of the 23 tumors (26%). In
      addition, a novel region of homozygous deletion was detected in six tumors (26%)
      at D9S126, approximately 2.5 cM proximal to p16/CDKN2. A single tumor contained a
      homozygous deletion at both the p16/CDKN2 locus and the D9S126 locus. The
      possibility of homozygous loss was confirmed by multiplex PCR using both the
      D9S126 marker and a chromosome 9p control marker. Fluorescence in situ
      hybridization analysis with P1 and cosmid probes containing D9S126 also confirmed
      these data. The minimum region of homozygous deletion was determined by testing
      markers immediately proximal and distal to the D9S126 region. The data identify a
      homozygous loss on the short arm of chromosome 9 suggesting the presence of a
      novel TSG locus, proximal to p16/CDKN2 and located between D9S265 and D9S259.

PMID- 8988030
TI  - A recurring translocation, t(3;6)(q27;p21), in non-Hodgkin's lymphoma results in
      replacement of the 5' regulatory region of BCL6 with a novel H4 histone gene.
AB  - 3q27 translocations affecting the BCL6 gene can involve not only immunoglobulin
      genes (IG) but also other as yet uncharacterized chromosomal loci as partners.
      Here, we describe cloning of the junctional area of a recurring translocation,
      t(3;6)(q27;p21), in non-Hodgkin's lymphoma of B-cell type and isolation of clones
      from 6p21; high resolution fluorescence in situ hybridization mapped the clones
      to sub-band 6p21.3. Nucleotide sequence analysis of a fragment from the
      junctional area of 6p21 revealed the presence of a novel H4 histone gene that was
      included in the histone gene cluster on this particular region, and the same
      fragment detected approximately 380-bp transcripts in hematological tumor cells.
      Breakpoints on 3q27 of two cases carrying t(3;6) were immediately 3' of the BCL6
      exon 1, and the H4 histone gene was substituted for the 5' regulatory elements of
      BCL6. Because H4 gene expression is tightly coupled to DNA replication, this
      study suggested an immediate mechanism for deregulated expression of BCL6,
      leading to the development of non-Hodgkin's lymphoma.

PMID- 8988031
TI  - Expression of reciprocal hybrid transcripts of HMGIC and FHIT in a pleomorphic
      adenoma of the parotid gland.
AB  - The developmentally regulated HMGIC gene, which encodes an architectural
      transcription factor, has recently been linked to the pathogenesis of benign
      solid tumors with chromosome aberrations involving 12q13-15. Among these tumors
      are pleomorphic adenoma of the salivary glands, lipoma, uterine leiomyoma,
      hamartomas of the breast and lung, fibroadenoma of the breast, angiomyxoma, and
      endometrial polyps. For most tumor types, however, the translocation partners are
      variable. At present, no translocation partner genes of HMGIC are known for
      pleomorphic adenomas. Here, we report that in a primary pleomorphic adenoma of
      the parotid gland, the FHIT gene, which spans the chromosome 3p14.2 fragile site
      FRA3B, and is frequently disrupted in tumors, acts as a fusion partner of HMGIC.
      In addition to normal HMGIC and FHIT transcripts, an HMGIC/FHIT hybrid transcript
      as well as its reciprocal counterpart, FHIT/HMGIC, were found to be expressed by
      reverse transcription-PCR. The results establish the concurrent disruption of two
      tumor-associated genes in a benign tumor.

PMID- 8988032
TI  - Human prostatic carcinoma oncogene PTI-1 is expressed in human tumor cell lines
      and prostate carcinoma patient blood samples.
AB  - Rapid expression cloning and differential RNA display identifies a gene, named
      prostate tumor inducing gene-1 (PTI-1), that is differentially expressed in
      prostate cancer versus normal prostate and benign prostatic hypertrophy. PTI-1
      encodes a truncated and mutated human elongation factor 1 alpha, and its 5'
      untranslated region (UTR) shares significant homology with the 23S rRNA gene of
      Mycoplasma hyopneumoniae. PCR with human genomic DNAs, using PTI-1 5' UTR
      specific primers, suggests that this sequence is part of the human genome.
      Furthermore, reverse transcription (RT)-PCR, with one primer specific to the 5'
      UTR region and the other to the elongation factor 1 alpha coding region,
      amplifies PTI-1 transcripts from total RNA of various human tumor cell lines and
      blood samples from prostate carcinoma patients. RT-PCR products with the
      predicted size and sequence of PTI-1 are detected in RNAs from cell lines of
      human prostate, breast, and colon carcinomas. This RT-PCR product is shown by
      Southern blotting and sequence analyses to contain the junction sequence between
      the 5' UTR and the coding region of the PTI-1 gene. Furthermore, RT-PCR analysis
      indicates that the PTI-1 gene is also expressed in prostate carcinoma patient
      derived blood samples. On the basis of serial dilution experiments, PTI-1 can
      detect 1 prostate carcinoma cell in 10(8) cells not expressing PTI-1. In this
      context, PTI-1 represents a sensitive marker for detecting human prostate cancer
      in the bloodstream. This study confirms the authenticity of the PTI-1 gene and
      documents its potential clinical utility as a sensitive and specific indicator of
      prostate cancer progression.

PMID- 8988033
TI  - ATM gene product phosphorylates I kappa B-alpha.
AB  - The recently cloned ATM gene is mutated in patients with ataxia telangiectasia,
      but its biological functions remain to be experimentally determined. Structural
      analysis has revealed ATM sequence similarities to the catalytic domains of
      phosphatidyl-3 kinase and other members of this family of yeast and mammalian
      proteins. Rabbit polyclonal antibodies raised against polypeptide regions unique
      to the COOH terminus and to the NH2 terminus of the published ATM sequence
      confirm ATM as M(r) approximately 350,000 protein in normal cells, which is
      missing in AT cells. Immunoprecipitated protein(s) is capable of phosphorylating
      I kappa B-alpha in an in vitro kinase assay. However, we did not observe a
      phosphatidyl-3 kinase or a DNA-dependent protein kinase function by ATM
      immunoprecipitates. These data support a protein kinase activity for ATM and
      suggest a role in NF-kappa B activation.

PMID- 8988034
TI  - Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human
      advanced esophageal carcinoma.
AB  - Growth factor receptors transmit intracellular signals that may be important in
      carcinogenesis. The Grb7 protein was recently identified as a substrate of the
      epidermal growth factor receptor and related Her2/ erbB2 receptor-linked tyrosine
      kinase activity. The Grb7 gene has been found to be coamplified with Her2/erbB2
      in breast carcinomas. In this study, Grb7 expression was studied in 32 human
      esophageal cancers. A human Grb7 cDNA encoding for N-terminal amino acids was
      isolated and found to be 90% homologous to the murine counterpart. Although there
      was no amplification of the Grb7 gene in esophageal cancers, Grb7 mRNA was found
      to be overexpressed in 14 cancers (43.8%) but not in adjacent normal esophageal
      mucosa. It is noteworthy that coexpression of Grb7 with epidermal growth factor
      receptor or Her2/erbB2 was detected in 10 esophageal carcinomas (31.3%) and was
      significantly related to extramucosal tumor invasion (P = 0.02), whereas such a
      relationship was not shown by each sole expression. These findings suggest a
      possible relationship of Grb7 signaling in association with expression of
      tyrosine kinase receptors in aggressive human esophageal cancer.

PMID- 8988035
TI  - Deletion within the D17S34 locus in a primitive neuroectodermal tumor.
AB  - Loss of heterozygosity on chromosome 17p13.3 is frequently observed in solid
      tumors, and the presence of a tumor suppressor gene has been predicted in this
      region of chromosome 17. We have analyzed a primitive neuroectodermal tumor
      sample exhibiting loss of heterozygosity at the D17S34 locus, a commonly used
      telomeric marker on the short arm of chromosome 17. The remaining allele showed a
      rearrangement. Cosmids spanning the D17S34 locus and probes from that region were
      used to demonstrate a 9-kb deletion within the D17S34 locus and were found to
      contain evolutionary, conserved sequences. Genetic alterations in this region may
      also affect expression of immediately adjacent genes, such as ABR, and could be a
      common mechanism in the causation of primitive neuroectodermal tumors.

PMID- 8988036
TI  - Methylation of the 5' CpG island of the endothelin B receptor gene is common in
      human prostate cancer.
AB  - Production of the potent vasoconstrictor endothelin-1 (ET-1) by human prostate
      cancer cells accompanies prostate cancer progression in vivo. The predominant
      endothelin receptor expressed by normal prostate epithelium, ETB, is not
      expressed by any of the established human prostate cancer cell lines, and ETB
      binding is decreased on prostate cancer tissues. ETB, which may mediate ET-1
      clearance and may inhibit ET-1 secretion, is encoded by a gene that contains a 5'
      CpG island encompassing the transcriptional regulatory region. We examined this
      regulatory region of the ETB receptor gene (EDNRB) to determine whether
      hypermethylation of cytidine nucleotides accompanies decreased ETB expression in
      human prostate cancer. We found somatic methylation of CpG island sequences in
      EDNRB in 5 of 5 human prostate cancer cell lines, 15 of 21 primary prostate
      cancer tissues, and 8 of 14 prostate cancer metastases (70% of samples overall).
      Normal tissues contained only unmethylated EDNRB. Treatment of human prostatic
      carcinoma cell line cultures with 5-azacytidine induced ETB mRNA expression,
      suggesting that CpG island methylation changes might accompany the apparent
      transcriptional silencing of EDNRB in vivo.

PMID- 8988037
TI  - Beta 4 integrin transfection of UM-UC-2 (human bladder carcinoma) cells: stable
      expression of a spontaneous cytoplasmic truncation mutant with rapid loss of
      clones expressing intact beta 4.
AB  - The alpha 6 beta 4 integrin is a component of the hemidesmosome, the anchoring
      structure in the basal membrane of epithelial cells. alpha 6 beta 4 expression is
      frequently altered in neoplastic cells. It is sometimes lost and sometimes
      overexpressed, which suggests that disruption of normal function is involved in
      neoplastic transformation. To examine the effect of this integrin on the growth
      and behavior of malignant cells that have lost beta 4, we transfected a full
      length beta 4 cDNA into the UM-UC-2 cell line that expresses alpha 6 but not beta
      4. Although large numbers of clones were obtained when a control vector was used
      in the transfection, only 12 clones could be isolated that expressed beta 4. Of
      these, only two beta 4-positive clones, clones 8 and 11, persisted long enough
      for further study. Clone 8 cells initially expressed beta 4, but within 2 weeks,
      all positive cells were lost from the culture. Clone 11 persisted in culture and
      retained strong surface expression of alpha 6 beta 4. Biochemical analysis and
      Western blotting revealed that this clone contained a truncated form of beta 4
      that had lost the distal cytoplasmic domain. We conclude that expression of wild
      type beta 4 in UM-UC-2 inhibits cell growth, presumably by an integrin-mediated
      signaling pathway. Clone 11 escaped from normal signaling because the cytoplasmic
      domain, a region essential for basal polar localization, was lost. The alpha 6
      beta 4 integrin appears to have tumor suppressor activity in epithelial tumors.

PMID- 8988038
TI  - Baculovirus P35 inhibits the glucocorticoid-mediated pathway of cell death.
AB  - Recent evidence suggests that members of the interleukin-1-beta-converting enzyme
      (ICE)/Ced-3 family are key mediators of mammalian apoptosis. The known members of
      the ICE/Ced-3 cysteine protease family are synthesized as proenzymes and require
      proteolytic processing to produce active, heterodimeric enzymes. The baculovirus
      protein P35 has recently been shown to inhibit several members of the ICE/Ced-3
      cysteine protease family. The importance of ICE/Ced-3 cysteine proteases in
      programmed cell death prompted us to investigate the role of the apoptotic
      mediator, CPP32, in the glucocorticoid-mediated cell death pathway.
      Glucocorticoids induce growth inhibition and apoptosis in sensitive leukemic cell
      lines, immature thymocytes, and eosinophils. In this report, we demonstrate the
      enzymatic cleavage of proCPP32 to its active subunits in cells undergoing
      glucocorticoid-induced apoptotic cell death. Concurrently, in apoptotic cells,
      PARP, a 116-kilodalton (kDa) human poly(ADP-ribose) polymerase, is
      proteolytically cleaved to its signature 85-kDa fragment. The proteolytic
      processing of PARP (the nuclear DNA repair enzyme known to be cleaved in
      association with apoptosis) is catalyzed by members of the ICE/Ced-3 family.
      Importantly, stable transfection of the antiapoptotic baculovirus P35 inhibits
      glucocorticoid-induced apoptotic cell death, proteolytic processing of proCPP32,
      and cleavage of the 116kDa PARP. We conclude that activation of CPP32 is a
      critical event in glucocorticoid-induced apoptosis and that this pathway is
      inhibited at or upstream of CPP32 by baculovirus P35. These data demonstrate that
      PARP cleavage occurs during glucocorticoid-induced apoptotic cell death and show
      that this proteolytic process is blocked by the expression of baculovirus P35,
      supporting a role for activation of the ICE/Ced-3-like cysteine protease during
      glucocorticoid-induced apoptosis.

PMID- 8988039
TI  - Reversal of loss of imprinting in tumor cells by 5-aza-2'-deoxycytidine.
AB  - To determine whether loss of imprinting in cancer might be reversed by altering
      DNA methylation, we treated tumor cells with 5-aza-2'-deoxycytidine, a specific
      inhibitor of cytosine DNA methyltransferase. Treated cells showed several
      significant and reproducible changes. (a) Equal expression of maternal and
      paternal alleles of insulin-like growth factor 2 switched to predominant
      expression of a single parental allele. (b) H19 expression was reactivated. (c)
      Biallelic H19 expression switched to monoallelic expression. (d) Biallelic
      methylation of H19 switched to preferential allelic methylation. These results
      imply that abnormally imprinted cells are susceptible to epigenetic modification
      and that the effect of 5-aza-2'-deoxycytidine on tumor cells with loss of
      imprinting is not random but specific to one allele.

PMID- 8988041
TI  - Nuclear protein patterns in normal T-lymphocytes and lymphoblastoid cells.
AB  - We compared the two-dimensional patterns of nuclear proteins obtained from normal
      quiescent T lymphocytes with those from normal proliferating T lymphocytes and
      three lymphoblastoid cell lines (CEM, Namalwa, and Molt-4). We identified sets of
      nuclear proteins which are specific for normal quiescent or normal proliferating
      T lymphocytes, or shared by the three lymphoblastoid cell lines and absent from
      the normal T cells. The protein patterns from two nuclear subfractions, i.e., S1
      fraction, obtained after nuclease extraction, and the nuclear matrix, were also
      analyzed. In S1 nuclear fraction, 6 proteins of 75 kDa [isoelectric point (pI)
      4.4], 55 kDa (pI 6.7), 41 kDa (pI 4.1), 39 kDa (pI 5.0), 32 kDa (pI 5.5), and 29
      kDa (pI 6.6) were found to be specifically present in normal quiescent cells but
      not in normal proliferating or lymphoblastoid cell lines. Five proteins of 23 kDa
      (pI 4.2), 23 kDa (pI 4.3), 22 kDa (pI 4.4), 21 kDa (pI 4.5), and 21 kDa (pI 4.6)
      were observed only in the S1 fraction of normal proliferating lymphocytes,
      whereas they were absent in normal quiescent cells and in the transformed cell
      lines. Eight proteins of 56 kDa (pI 4.7), 50 kDa (pI 4.6), 45 kDa (pI 4.4), 43
      kDa (pI 4.3), 42 kDa (pI 4.3), 41 kDa (pI 4.3), 43 kDa (pI 4.2), and 42 kDa (pI
      4.1) were found only in the nuclear matrix of normal quiescent cells. Moreover,
      two doublets of proteins of 31-33 kDa (pI 4.3) and 31-33 kDa (pI 4.2) were found
      only in the nuclear matrix of the normal proliferating cells and three proteins
      of 37 kDa (pI 3.8), 37 kDa (pI 3.7), and 35 kDa (pI 4.5) were specifically
      present in the nuclear matrix of the lymphoblastoid cells lines, but not in
      normal quiescent or activated lymphocytes.

PMID- 8988040
TI  - [D-Arg1,D-Trp5,7,9,Leu11]substance P: a novel potent inhibitor of signal
      transduction and growth in vitro and in vivo in small cell lung cancer cells.
AB  - [D-Arg1,D-Trp5,7,9,Leu11]Substance P (SP) was identified out of a panel of novel
      SP analogues as the most potent inhibitor of small cell lung cancer (SCLC) cell
      growth. This analogue inhibited proliferation of H-510 and H-69 SCLC cells in
      liquid culture and in semisolid media (IC50, 5 microM). Colony formation
      stimulated by multiple neuropeptides, including vasopressin and bradykinin, was
      also blocked by [D-Arg1,D-Trp5,7,9,Leu11]SP. This new SP analogue inhibited
      vasopressin- or bradykinin-induced Ca2+ mobilization and mitogen-activated
      protein kinase activation. Administration of [D-Arg1,D-Trp5,7,9,Leu11]SP
      inhibited the growth of an H-69 xenograft in nude mice. Our results support the
      hypothesis that SP analogue broad-spectrum neuropeptide antagonists could be of
      therapeutic value in SCLC.

PMID- 8988042
TI  - Bcl-2 and Bcl-XL antagonize the mitochondrial dysfunction preceding nuclear
      apoptosis induced by chemotherapeutic agents.
AB  - A number of apoptosis-inducing agents used in cancer therapy (etoposide,
      doxorubicin, 1-beta-D-arabinofuranosylcytosine), as well as the proapoptotic
      second messenger ceramide, induce a disruption of the mitochondrial transmembrane
      potential (delta psi m) that precedes nuclear DNA fragmentation. This effect has
      been observed in tumor cell lines of T-lymphoid, B-lymphoid, and myelomonocytic
      origin in vitro. Circulating tumor cells from patients receiving chemotherapy in
      vivo also demonstrate a delta psi m disruption after in vitro culture that
      precedes nuclear apoptosis. Transfection-enforced hyperexpression of the proto
      oncogenes bcl-2 and bcl-XL protects against chemotherapy-induced apoptosis, at
      both the level of the mitochondrial dysfunction preceding nuclear apoptosis and
      the level of late nuclear apoptotic events. Bcl-2-mediated inhibition of ceramide
      induced delta psi m disruption is observed in normal as well as anucleate cells,
      indicating that bcl-2 acts on an extranuclear pathway of apoptosis. In contrast
      to Bcl-2 and Bcl-XL, hyperexpression of the protease inhibitor cytokine response
      modifier A fails to protect tumor cells against chemotherapy-induced delta psi m
      disruption and apoptosis, although cytokine response modifier A does prevent the
      delta psi m collapse and posterior nuclear apoptosis triggered by cross-linking
      of Fas/Apo-1/CD95. In conclusion, delta psi m disruption seems to be an
      obligatory step of early (pre-nuclear) apoptosis, and delta psi m is stabilized
      by two members of the bcl-2 gene family conferring resistance to chemotherapy.

PMID- 8988043
TI  - DNA-dependent protein kinase is not required for accumulation of p53 or cell
      cycle arrest after DNA damage.
AB  - In response to DNA damage, cells transduce a signal that leads to accumulation
      and activation of p53 protein, transcriptional induction of several genes,
      including p21, gadd45, and gadd153, and cell cycle arrest. One hypothesis is that
      the signal is mediated by DNA-dependent protein kinase (DNA-PK), which consists
      of a catalytic subunit (DNA-PKcs) and a regulatory subunit (Ku). DNA-PK has
      several characteristics that support this hypothesis: Ku binds to DNA damaged by
      nicks or double-strand breaks, DNA-PKcs is activated when Ku binds to DNA, DNA-PK
      will phosphorylate p53 and other cell cycle regulatory proteins in vitro, and DNA
      PKcs shares homology with ATM, which is mutated in ataxia telangiectasia and
      involved in signaling the p53 response to ionizing radiation. The hypothesis was
      tested by analyzing early passage fibroblasts from severe combined
      immunodeficient mice, which are deficient in DNA-PK. After exposure to ionizing
      radiation, UV radiation, or methyl methane-sulfonate, severe combined
      immunodeficient and wild-type cells were indistinguishable in their response. The
      accumulation of p53, induction of p21, gadd45, and gadd153, and arrest of the
      cell cycle in G1 and G2 occurred normally. Therefore, DNA-PK is not required for
      the p53 response or cell cycle arrest after DNA damage.

PMID- 8988044
TI  - Energy balance and colon cancer--beyond physical activity.
AB  - Low levels of physical activity and high levels of energy intake and body mass
      have all been directly associated with colon cancer. The purpose of this study
      was to determine how physical inactivity interacts with other components of
      energy balance (energy intake and body mass) in determining colon cancer risk.
      Data were obtained from 2073 first primary cases of colon cancer and 2466 age-
      and sex-matched controls identified from 8 counties in Utah, the Northern
      California Kaiser Permanente Medical Care Program, and the Twin Cities
      metropolitan area in Minnesota. Recent and lifetime physical activity was
      assessed by intensity of activities performed at home, leisure, and at work;
      energy intake was estimated from an extensive diet history questionnaire; and
      body mass index (BMI) was calculated from measured height at the time of
      interview and reported weight for the referent year. For both men and women, lack
      of lifetime vigorous leisure-time activity was associated with increased risk of
      colon cancer [odds ratio (OR), 1.63 and 95% confidence interval (CI), 1.26-2.12
      for men and OR, 1.59 and 95% CI, 1.21-2.10 for women, comparing the lowest to
      highest level of activity]. There were no differences in risk associated with
      physical activity by tumor site within the colon or by age at diagnosis. High
      levels of energy intake were also associated with increased risk of colon cancer
      in men and women (OR, 1.74 and 95% CI, 1.14-2.67 for men and OR, 1.70 and 95% CI,
      1.07-2.70 for women). A large BMI was more associated with increased risk in men
      (OR, 1.94 and 95% CI, 1.49-2.54) than in women (OR, 1.45 and 95% CI, 1.08-1.94).
      Those at greatest risk of colon cancer were those who had the most unfavorable
      energy balance in that they were physically inactive, had high energy intakes,
      and had a large BMI (OR, 3.35 and 95% CI, 2.09-5.35). However, when physical
      activity was high, having a high energy intake and large BMI resulted in a
      nonsignificant increased colon cancer risk (OR, 1.28 and 95% CI, 0.81-2.03). This
      pattern was consistent between the sexes, but there was some evidence that men
      may be at higher risk than women, especially older women, as a result of
      unfavorable energy balance. These results support previous findings that physical
      inactivity, high energy intake, and large body mass are associated with increased
      risk of developing colon cancer. However, energy balance as a whole seems to be
      associated with risk of colon cancer. These findings suggest systemic metabolic
      influences on carcinogenesis and have important implications for prevention.

PMID- 8988045
TI  - Inhibition of angiogenesis and breast cancer in mice by the microtubule
      inhibitors 2-methoxyestradiol and taxol.
AB  - 2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite which disrupts
      microtubule function, has been shown to inhibit proliferating cells in vitro and
      suppress certain murine tumors in vivo. In vitro screening has determined that
      breast cancer cell lines are most sensitive to inhibition by 2-ME. Additionally,
      2-ME has been shown to inhibit angiogenesis in vitro. We tested whether 2-ME
      suppresses cytokine-induced angiogenesis in vivo and inhibits growth of a human
      breast carcinoma in severe combined immunodeficient mice. A model of basic
      fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF)
      induced corneal neovascularization in C57BL/6 mice was used to evaluate the
      antiangiogenic effects of 2-ME and other microtubule inhibitors such as Taxol,
      vincristine, and colchicine. 2-ME (150 mg/kg p.o., n = 20) inhibited bFGF and
      VEGF-induced neovascularization by 39% and 54%, respectively. Taxol (6 mg/kg
      i.p., n = 17) inhibited bFGF and VEGF-induced neovascularization by 45% and 37%,
      respectively. Vincristine (0.2 mg/kg i.p., n = 8) and colchicine (0.25 mg/kg
      i.p., n = 8) had no effect. Treatment with 2-ME (75 mg/kg p.o., n = 9) for 1
      month suppressed the growth of a human breast carcinoma in mice by 60% without
      toxicity. Recognition of the antiangiogenic and antitumor properties of 2-ME and
      Taxol may be crucial in planning clinical applications to angiogenesis-dependent
      diseases.

PMID- 8988046
TI  - Identification of naturally processed human ovarian peptides recognized by tumor
      associated CD8+ cytotoxic T lymphocytes.
AB  - Identification of naturally processed peptides recognized by tumorspecific CTLs
      may lead to epitope-specific tumor vaccines. Because these epitopes may be
      expressed differently on epithelial tumors and may differ in their ability to
      induce CTL in vivo, we have isolated the HLA-A2-peptide complexes by
      immunoaffinity from an established ovarian tumor line transfected with and
      expressing HLA-A2 gene. High-performance liquid chromatography-fractionated
      peptides were used to reconstitute epitopes recognized on HLA-A2 by three HLA-A2+
      CD8+ CTL lines. These lines recognized at least three of the same groups of
      fractions (designated SKOV3.A, -B, and -C) but showed differences in the pattern
      of recognition of other fractions. To gain insight in the epitope distribution by
      freshly isolated ovarian tumors, we compared the recognition of peaks SKOV3.B and
      -C with the corresponding peaks from an ovarian tumor (OVA-6) that expressed
      similar levels of HLA-A2, using one of these lines (CTL-OVA-5) as indicator. CTL
      OVA-5 recognized a large number of epitopes from peaks B and C rechromatographed
      on more resolving high-performance liquid chromatography gradient. Although a
      number of peaks appeared to be coincident on both SKOV3 and OVA-6, an even higher
      number appeared either not to overlap or to overlap only partially. These
      findings, which represent the first analysis of the epitopes presented by a
      patient tumor, suggest that the use of tumor line-derived peptides for
      vaccination may require selection of the epitopes corresponding to the ones
      presented by freshly isolated human tumors.

PMID- 8988047
TI  - Prevention of adenocarcinoma colon 26-induced cachexia by interleukin 10 gene
      transfer.
AB  - A s.c. injection of a mouse colon adenocarcinoma cell line, colon 26 clone 20,
      induced cachexia, as evidenced by progressive weight loss and severe
      hypoglycemia. Several lines of evidence indicate that a pro-inflammatory
      cytokine, interleukin 6 (IL-6), plays a major role, albeit partially, in the
      establishment of cachexia in this model. Because IL-10 can potentially inhibit
      the production of pro-inflammatory cytokines including IL-6, we evaluated the
      effects of IL-10 gene transfer on the establishment of cachexia. IL-6 transcript
      was detected at tumor sites of mice inoculated with parental or control vector
      transfectant cells, and serum IL-6 levels were markedly increased in these mice.
      The injection of parental cells into IL-6-deficient mice induced cachexia with
      elevated serum IL-6 levels comparable to wild-type mice, indicating that tumor
      cells are a major source of IL-6. The inoculation of IL-10-transfectant cells
      kept IL-10 mRNA expression at tumor sites and induced the elevation in serum IL
      10 levels without affecting the growth rates of colon 26 cells both in vitro and
      in vivo. However, the implantation with IL-10-transfectant cells reduced the
      expression of IL-6 mRNA at the tumor sites and the elevation in serum IL-6
      levels. Concomitantly, mice inoculated with IL-10-transfectant cells did not
      exhibit progressive weight loss, a reduction in food intake, or severe
      hypoglycemia, which was observed in mice inoculated with parental or control
      vector-transfectant cells. Collectively, these results suggest that IL-10 gene
      transfer prevented the occurrence of cachexia with a concomitant inhibition of IL
      6 production at the tumor sites.

PMID- 8988048
TI  - Effect of linker variation on the stability, potency, and efficacy of carcinoma
      reactive BR64-doxorubicin immunoconjugates.
AB  - The internalizing anti-Le(y) monoclonal antibody (MAb) BR64 was conjugated to the
      anticancer drug doxorubicin (DOX) using an acid-labile hydrazone bond to the DOX
      and either a disulfide or thioether bond to the MAb. The resulting disulfide
      (BR64-SS-DOX) and thioether (BR64-S-DOX) conjugates were evaluated for stability,
      potency, and antigen-specific activity in both in vitro and in vivo model
      systems. The BR64-SS-DOX conjugates demonstrated antigen-specific activity both
      in vitro and when evaluated against antigen-expressing, DOX-sensitive human
      carcinoma xenografts. However, the stability and potency of disulfide conjugates
      were poor, and in vivo activity superior to unconjugated DOX was seen only at
      doses approaching the maximum tolerated dose. Furthermore, BR64-SS-DOX conjugates
      were not active against antigen-expressing, DOX-insensitive colon tumor
      xenografts. In contrast, the BR64-S-DOX conjugates demonstrated good stability
      both in vitro and in vivo. The increased stability of the BR64-S-DOX conjugates
      resulted in the delivery of more biologically active DOX to tumors with a
      concomitant increase in potency and efficacy over that which could be achieved
      with either unconjugated DOX or BR64-SS-DOX conjugates. Delivery of DOX by BR64
      SS-DOX conjugates resulted in complete regressions and cures of both DOX
      sensitive lung xenografts and DOX-intensitive colon tumor xenografts. These
      results demonstrate the importance of linker stability when delivering drugs such
      as DOX to carcinomas via internalizing antibodies and are likely to have direct
      relevance to the clinical utility of MAb-directed delivery.

PMID- 8988049
TI  - Localization of a novel tumor suppressor locus on human chromosome 3q important
      in osteosarcoma tumorigenesis.
AB  - Mitotic recombination org nondysjunction are common mechanism for tumor-specific
      loss of constitutional heterozyosity (LOH) and tumor suppressor allelic
      inactivation and can be useful in localizing new putative tumor suppressor genes.
      In osteosarcoma, the highest frequencies of LOH have been reported for
      chromosomes 3q, 13q, 17p, and 18q. The high incidence of LOH on chromosome 3q
      suggests the presence of a novel tumor suppressor gene. To localize this putative
      tumor suppressor gene, we have used polymorphic markers on chromosome 3q to
      define the minimal region in which mitotic recombination or deletion results in
      LOH, which should contain the tumor suppressor gene. This putative tumor
      suppressor has been localized to a region between 3q26.2-3q26.3 of less that 1 cM
      between the polymorphic loci D3S1212 and D3S1246.

PMID- 8988050
TI  - Overexpression of DNA polymerase beta sensitizes mammalian cells to 2',3'
      deoxycytidine and 3'-azido-3'-deoxythymidine.
AB  - Mammalian DNA polymerase beta is a DNA repair enzyme expressed constitutively at
      a low level. In vitro, purified DNA polymerase (Pol) beta incorporates the
      nucleotide analogues 2'-3' deoxycytidine (ddC)-triphosphate and 3'-azido-3'
      deoxythymidine (AZT)-triphosphate into DNA, causing chain termination. We have
      tested the possibility of enhancing the cytotoxicity of these chain terminators
      against mammalian cells by increasing the level of Pol beta. Chinese hamster
      ovary AA8 and murine melanoma B16 cell lines were stably transfected with rat pol
      beta cDNA under the control of a viral enhancer/promoter. We found that
      overexpression of Pol beta sensitized the cells to ddC and AZT. To confirm the
      role of this polymerase in this process, we prepared cell extracts from the
      control and Pol beta overexpressing Chinese hamster ovary cell lines and tested
      in vitro their capacity to incorporate ddC-triphosphate and AZT-triphosphate into
      DNA. We found that inhibition of DNA replication by both chain terminators was
      more pronounced when extracts from pol beta-transfected cells were used,
      providing a direct evidence of the involvement of Pol beta in the sensitization
      process. In addition, we showed that cotransfection with bacterial or viral
      thymidine/thymidylate kinase genes enhanced the Pol beta-mediated cytotoxicity of
      AZT, suggesting that phosphorylation and polymerization activities might be
      combined to potentiate their respective effects. These observations may be useful
      for improving therapeutic efficiency of DNA chain terminators.

PMID- 8988051
TI  - MLL self fusion mediated by Alu repeat homologous recombination and prognosis of
      AML-M4/M5 subtypes.
AB  - Fifty-six patients with de novo acute myeloid leukemia M4/M5 subtypes were
      studied for rearrangements of the mixed lineage leukemia gene, MLL (also called
      HRX, Htrx-1, or ALL-1). Ten patients (18%) showed rearrangements of the MLL gene,
      9 in a major breakpoint cluster region within a centromeric 8.3-kb BamHI
      fragment, whereas rearrangement in one patient was the result of a direct tandem
      duplication of exons 2-6 of MLL. Analysis of sequences at the duplication
      junction revealed that the points of MLL fusion within introns 6 and 1 both lie
      within Alu elements. This suggests the involvement of Alu repeat mediated
      homologous recombination in MLL self fusion. For the 10 rearranged samples,
      cytogenetics analysis revealed a normal karyotype in 3, and 3 had abnormalities
      other than 11q23. Survival analysis of patients revealed no difference between
      those with rearrangement of MLL and those showing the germ-line configuration.

PMID- 8988052
TI  - Aberrant cell growth induced by avian winged helix proteins.
AB  - Winged helix transcription factors act as important regulators of embryonal
      development and tissue differentiation in vertebrates and invertebrates.
      Identification of the retroviral oncogene v-qin as a member of the winged helix
      family showed that these developmental regulators also have oncogenic potential.
      We used low-stringency hybridization of a chicken embryonic cDNA library to
      isolate cDNA clones coding for the three chicken winged helix (CWH) proteins, CWH
      1, CWH-2, and CWH-3. The CWH genes are transcribed in a tissue-restricted pattern
      in adult and embryonic chicken tissues. The CWH proteins bind to conserved DNA
      binding sites for winged helix proteins in a sequence-specific manner. Expression
      of the CWH proteins from replication-competent retroviral RCAS vectors induces
      changes in morphology and growth pattern of chicken embryo fibroblasts. CWH-1 and
      CWH-3 also induce anchorage-independent growth in agar. Chicken embryo
      fibroblasts expressing the RCAS constructs release replication-competent viruses
      that are able to elicit the same cellular changes as the parental plasmid DNA.
      Our results suggest that winged helix transcription factors not only function as
      regulators of development and differentiation but also have the potential to
      stimulate abnormal cell proliferation.

PMID- 8988053
TI  - Raf-1/bcl-2 phosphorylation: a step from microtubule damage to cell death.
AB  - Recent studies have shown that paclitaxel leads to activation of Raf-1 kinase and
      have suggested that this activation is essential for bcl-2 phosphorylation and
      apoptosis. In the present study, we demonstrate that, in addition to paclitaxel,
      other agents that interact with tubulin and microtubules also induce Raf-1/bcl-2
      phosphorylation, whereas DNA-damaging drugs, antimetabolites, and alkylating
      agents do not. Activation of Raf-1 kinase by paclitaxel is linked to tubulin
      polymerization; the effect is blunted in paclitaxel-resistant cells, the tubulin
      of which does not polymerize following the addition of paclitaxel. In contrast,
      vincristine and vinblastine, drugs to which the paclitaxel-resistant cells retain
      sensitivity were able to bring about Raf-1 phosphorylation. The requirement for
      disruption of microtubules in this signaling cascade was strengthened further
      using paclitaxel analogues by demonstrating a correlation between tubulin
      polymerization, Raf-1/bcl-2 phosphorylation, and cytotoxicity. Inhibition of RNA
      or protein synthesis prevents Raf-1 activation and bcl-2 phosphorylation,
      suggesting that an intermediate protein(s) acts upstream of Raf-1 in this
      microtubule damage-activating pathway. A model is proposed that envisions a
      pathway of Raf-1 activation and bcl-2 phosphorylation following disruption of
      microtubular architecture, serving a role similar to p53 induction following DNA
      damage.

PMID- 8988054
TI  - Two mechanisms of basic fibroblast growth factor-induced angiogenesis in bladder
      cancer.
AB  - In the urine of patients with bladder cancer, levels of the angiogenio peptide
      basic fibroblast growth factor (bFGF) may be elevated 100-fold. To date, levels
      of expression of bFGF in bladder tumor tissue have not been determined, nor has
      the cellular source of the urinary bFGF been identified. bFGF mRNA expression was
      quantified using RNase protection analysis in 32 primary bladder tumors and 8
      normal bladder specimens. In addition, bFGF protein expression in the tumor
      cytosol was determined using a Quantikine ELISA, and bFGF protein expression was
      localized with immunohistochemistry. bFGF mRNA expression was absent in 28 of 32
      (87%) bladder cancers despite detectable expression in 7 of 8 (87%) normal
      bladder specimens (P = 0.0001). In only one tumor was bFGF mRNA expression higher
      than in normal bladder tissue. Median bFGF protein expression was also higher in
      the normal bladder specimens than in the superficial tumors (3800 pg/g protein
      versus 1140 pg/g protein; P < 0.02), but there was no statistically significant
      difference between protein expression in normal bladder and invasive cancers
      (3800 pg/g versus 3600 pg/g). Median bFGF protein expression was higher in
      invasive cancers than in superficial tumors (P < 0.05). Intense bFGF
      immunoreactivity was seen in the basal lamina of normal transitional epithelium,
      in normal human detrusor muscle, and in vessels within tumors. Tumor cell
      immunoreactivity was rare and was usually weak. Only in the tumor which strongly
      overexpressed bFGF mRNA and protein was cytoplasmic staining detectable in the
      neoplastic cells. There are two mechanisms of bFGF-induced angiogenesis in
      bladder cancer. Rarely, neoplastic cells synthesize bFGF but more commonly bFGF
      is released by degradation of epithelial basement membranes and detrusor muscle,
      from where it can diffuse into the tumor microenvironment and bind to blood
      vessels. Mechanisms of extracellular matrix degradation may be important in
      bladder cancer angiogenesis and progression and as such are potential therapeutic
      targets.

PMID- 8988055
TI  - Interleukin-6 as a paracrine and autocrine growth factor in human prostatic
      carcinoma cells in vitro.
AB  - Interleukin (IL)-6 plays a significant role in genitourinary carcinomas. The
      present study was conducted to define the role of IL-6 in the growth of prostatic
      carcinoma and benign prostatic hyperplasia (BPH). An in vitro experiment was
      carried out using human prostatic carcinoma cell lines (LNCaP, which is androgen
      sensitive and slow growing, and DU145 and PC3, which are androgen insensitive and
      fast growing), and primary human epithelial and stromal cells derived from BPH.
      Cells were treated with recombinant human IL-6 or conditioned medium (CM) derived
      from the above cultured cells to identify possible paracrine and autocrine
      pathways. LNCaP was clearly responsive to exogenous IL-6 and to the CM derived
      from stromal cells, but not to the CM from LNCaP cells (P < 0.001). DU145 and PC3
      were slightly stimulated to grow by exogenous IL-6 and the CM derived from both
      stromal and respective homologous cells (P < 0.01). In contrast, BPH-derived
      epithelial cells showed little or no response to IL-6. The stimulatory effect of
      CM on prostatic carcinoma cells was significantly reduced by the addition of anti
      IL-6 antibody to the culture medium. Furthermore, the growth of DU145 and PC3 in
      serum-free medium was also inhibited by anti-IL-6 antibody (P < 0.001). All cell
      lines tested, except for LNCaP, secreted IL-6 into the culture medium. Results of
      reverse transcriptase-PCR analysis indicated that IL-6 receptor mRNA was present
      in all carcinoma cell lines but not in epithelial cells or stromal cells derived
      from BPH. These results suggest that IL-6 functions as a paracrine growth factor
      for LNCaP and as an autocrine growth factor for DU145 and PC3, but it has no
      stimulatory effect on epithelial cells derived from BPH.

PMID- 8988056
TI  - Altered nuclear matrix protein profiles in oncogene-transformed mouse fibroblasts
      exhibiting high metastatic potential.
AB  - The nuclear matrix provides the structural support of the nucleus and is involved
      in various cellular functions of the nucleus. Nuclear matrix proteins, which are
      both tissue and cell type specific, are altered with transformation and state of
      differentiation. Here, nuclear matrix protein profiles of oncogene-transformed
      mouse fibroblasts with various degrees of metastatic activity were analyzed using
      two-dimensional gel electrophoresis. This study shows that as the metastatic
      potential increases, similar nuclear matrix protein profiles are associated with
      each increase regardless of transformation agent.

PMID- 8988057
TI  - Glutathione metabolism in patients with non-small cell lung cancers.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the
      United States. Because NSCLC is highly chemoresistant, it is, usually not
      treatable. Altered glutathione (GSH) metabolism is thought to be one major
      mechanism of chemoresistance, and GSH levels are reported to be elevated in
      NSCLC. The main objective of this study is to delineate the potential mechanisms
      involved in elevation of tissue GSH, including extraction from the circulation by
      NSCLC. Twenty consecutive patients with NSCLC were enrolled. At the time of
      lobectomy, pulmonary artery and vein were identified, and blood flow was measured
      by an electromagnetic probe. Subsequently, blood samples were drawn from
      pulmonary artery, the vein draining the tumor-bearing lobe, and a normal lobe.
      Immediately after lobectomy, tumor and lung specimens were snap frozen. NSCLC
      tumor specimens had higher levels of GSH compared with lung tissue (20.8 +/- 9.4
      versus 11.6 +/- 3.0 nmol/mg protein, respectively; P < 0.05). The tumor
      demonstrated higher activity of the enzyme gamma-glutamyl transpeptidase, a
      membrane-bound enzyme involved in transmembrane uptake of GSH, than lung tissue
      (41.9 +/- 26.4 versus 22.4 +/- 12.3 units/mg protein, respectively; P < 0.05).
      Also, the tumor-bearing lobe showed elevated extraction of GSH and two of its
      component amino acids compared with lung tissue (GSH uptake: 0.60 +/- 0.67 versus
      0.20 +/- 0.40 microM/min, respectively; P < 0.05). NSCLC tumors are able to
      extract circulating GSH and its constituent amino acids to synthesize
      intracellular GSH. Increased activity of gamma-glutamyl transpeptidase may be one
      mechanism underlying increased GSH uptake by NSCLC.

PMID- 8988058
TI  - Sigma 2 receptors as potential biomarkers of proliferation in breast cancer.
AB  - sigma 1 and sigma 2 receptors have been shown to exist in a number of rodent and
      human tumor cell lines. Although their expression is heterogeneous and their
      function is unknown, sigma receptors have been proposed as potential targets for
      diagnostic tumor-imaging agents. In this study, the density of sigma 2 receptors
      in proliferative (P) and quiescent (Q) cells of the mouse mammary adenocarcinoma,
      line 66, was examined. Scatchard analyses of sigma 2 receptors were performed on
      membrane preparations of 66 P cells from 3-day cultures and 66 Q cells from 7-,
      10-, and 12-day cultures. The Scatchard studies revealed that 66 P cells had
      approximately 10 times more sigma 2 receptors/cell than the 66 Q cells from 10
      day cultures. Although > 97% of the cells were quiescent after 7 days in culture,
      the maximum differential in the sigma 2 expression between 66 P and 66 Q cells
      was not attained until these cells had been in culture for 10 days. These data
      suggest that ligands labeled with positron-emitting or single photon-emitting
      radionuclides, which selectively bind sigma 2 receptors, have the potential to
      noninvasively assess the proliferative status of human breast tumors.

PMID- 8988059
TI  - A novel retinoic acid receptor-selective retinoid, ALRT1550, has potent antitumor
      activity against human oral squamous carcinoma xenografts in nude mice.
AB  - We have identified a novel retinoid, ALRT1550, that potently and selectively
      activates retinoic acid receptors (RARs). ALRT1550 binds RARs with Kd values of
      approximately equal to 1-4 nM, and retinoid X receptors with low affinities (Kd
      approximately equal to 270-556 nM). We studied the effects of ALRT1550 on
      cellular proliferation in squamous carcinoma cells. ALRT1550 inhibited in vitro
      proliferation of UMSCC-22B cells in a concentration-dependent manner with an IC50
      value of 0.22 +/- 0.1 (SE) nM. 9-cis-Retinoic acid (ALRT1057), a pan agonist
      retinoid that activates RARs and retinoid X receptors, inhibited proliferation
      with an IC50 value of 81 +/- 29 nM. In vivo, as tumor xenografts in nude mice,
      UMSCC-22B formed well-differentiated squamous carcinomas, and oral administration
      (daily, 5 days/week) of ALRT1550, begun 3 days after implanting tumor cells,
      inhibited tumor growth by up to 89% in a dose-dependent manner over the range of
      3-75 micrograms/kg. ALRT1550 (30 micrograms/kg) also inhibited growth of
      established tumors by 72 +/- 3% when tumors were allowed to grow to approximately
      equal to 100 mm3 before dosing began. In comparison, 9-cis retinoic acid at 30
      mg/kg inhibited growth of established tumors by 73 +/- 5%. Interestingly,
      retinoids did not appear to alter tumor morphologies in UMSCC-22B tumors.
      Notably, ALRT1550 produced a therapeutic index of approximately equal to 17 in
      this model, indicating a separation between doses that inhibited tumor growth and
      that induced symptoms of hypervitaminosis A. In summary, ALRT1550 potently
      inhibits cellular proliferation in vitro and in vivo in this squamous cell
      carcinoma tumor model. These data support additional study of ALRT1550 for its
      potential for improving anticancer therapy in human clinical trials.

PMID- 8988060
TI  - Concurrent overexpression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4) in
      intestinal adenomas from multiple intestinal neoplasia (Min) mice and human
      familial adenomatous polyposis patients.
AB  - We postulated that increased expression of the cell cycle regulators cyclin D1
      and cyclin-dependent kinase (Cdk) 4 may be involved in the development of
      intestinal adenomas associated with familial adenomatous polyposis (FAP). In the
      present study of multiple intestinal neoplasia (Min) mice and human FAP patients,
      the expression and distribution of cyclin D1, Cdk4, and cell proliferative
      activity (5-bromo-2'-deoxyuridine incorporation) in normal and adenomatous
      intestinal epithelium were investigated. Immunohistochemical analysis of Min
      mouse intestine revealed that cyclin D1 immunoreactivity in the intestinal
      epithelium was restricted to the adenomatous areas, with a significantly higher
      percentage of positively staining nuclei in high-grade dysplasia versus low-grade
      dysplasia (54.8 +/- 18.4% versus 34.6 +/- 16.9%, P = 0.016). Morphologically
      normal areas of intestinal epithelia were uniformly negative for cyclin D1
      immunoreactivity. Cdk4 nuclear immunoreactivity was restricted to the crypt areas
      in morphologically normal small intestine and colon. Conversely, Cdk4
      immunoreactivity was uniformly abundant in adenomatous areas regardless of the
      degree of dysplasia. Increased expression of cyclin D1 and Cdk4 in adenomas was
      accompanied by a significantly increased 5-bromo-2'-deoxyuridine incorporation
      rate in the same areas. Immunoblot analysis of lysates from surgical specimens
      revealed increased levels of cyclin D1 and Cdk4 in the majority of intestinal
      adenomas from human FAP patients in comparison to the adjacent grossly normal
      colonic mucosa. Our results indicate that overexpression of cyclin D1 and Cdk4
      occurs in intestinal adenomas and is associated with increased cell proliferative
      activity in premalignant neoplastic cells. Increased cyclin D1 immunoreactivity
      is associated with more severe dysplasia. These data suggest that abnormal up
      regulation of these important G1 cell cycle proteins is a relatively early event
      in intestinal carcinogenesis and that these changes may contribute to malignant
      progression within those lesions.

PMID- 8988061
TI  - p53 status affects the rate of the onset but not the overall extent of
      doxorubicin-induced cell death in rat-1 fibroblasts constitutively expressing c
      Myc.
AB  - To better understand the effects of p53 on the process of DNA damage-induced cell
      death, we examined the influence of p53 status on the rate of the onset and the
      overall extent of cell death induced by doxorubicin. We performed this study with
      Rat-1 fibroblasts, with Rat-1/myc cells which constitutively express c-Myc, and
      with Rat-1/myc/p53His175 cells derived from Rat-1/myc cells, which, in addition,
      express the full-length dominant-negative p53His175 mutant gene. The p53His175
      mutant suppresses the transactivation function of endogenous p53 in these cells.
      In contrast to the parental Rat-1 cells, which exhibited only low levels of
      apoptosis within the first 24 h of treatment with 0.1 to 1 microM doxorubicin,
      similarly treated Rat-1/myc cells underwent massive and rapid apoptosis.
      Introduction of p53His175 into Rat-1/myc cells reversed this effect, indicating
      that Myc-accelerated doxorubicin-induced apoptosis requires functional p53.
      However, when the overall extent of cell death was measured using clonogenic
      assays, we found that greater than 90% of cells did not survive upon a 24-h
      pretreatment with doxorubicin at a concentration as low as 0.1 microM. Moreover,
      the effect of doxorubicin on all three cell lines was similar, irrespective of
      their p53 or c-Myc status. Taken together, our experiments indicate that: (a)
      constitutive expression of c-Myc accelerates the onset of doxorubicin-induced
      apoptosis in Rat-1 fibroblasts; (b) wild-type p53 function is necessary for this
      acceleration; and (c) neither overexpression of c-Myc nor the p53 status
      influences the overall extent of doxorubicin-induced cell death.

PMID- 8988062
TI  - Interpatient variability in bioavailability is related to the extent of
      absorption: implications for bioavailability and bioequivalence studies.

PMID- 8988063
TI  - Recombinant protein and therapeutic monoclonal antibody drug development in the
      United States from 1980 to 1994.

PMID- 8988064
TI  - Population pharmacodynamic model for ketorolac analgesia.
AB  - OBJECTIVE: To derive a population pharmacokinetic-pharmacodynamic model that
      characterizes the distribution of pain relief scores and remedication times
      observed in patients receiving intramuscular ketorolac for the treatment of
      moderate to severe postoperative pain. BACKGROUND: The data analysis approach
      deals with the complexities of analyzing analgesic trial data: (1) repeated
      measurements, (2) ordered categorical response variables, and (3) nonrandom
      censoring because the patients can take a rescue medication if their pain relief
      is insufficient. METHODS: Patients (n = 522) received a single oral or
      intramuscular administration of placebo or a single intramuscular dose of 10, 30,
      60, or 90 mg ketorolac for postoperative pain relief. Pain relief was measured
      periodically with use of a five-category ordinal scale up to 6 hours after
      dosing. In this period, 288 patients received additional medication because of
      insufficient pain relief. Pharmacokinetic data was available for 85 subjects.
      Models were fitted to the data with the NONMEM program. RESULTS: The
      pharmacokinetic data was best described by a two-compartment model with first
      order absorption. Pain relief was found to be a function of drug concentration
      (Emax model), time (waxing and waning of placebo effect), and an individual
      random effect. The drug concentration at half-maximal effect (EC50) and the first
      order rate constant (keo) half-life for pain relief were 0.37 mg/L and 24
      minutes. The probability of remedication was found to be a function of the
      observed level of pain relief and was found to increase with time. Monte Carlo
      simulations showed that adequate pain relief was achieved in 50% of the patients
      at 41, 27, 23, and 21 minutes after 10, 30, 60, or 90 mg of intramuscular
      ketorolac. Adequate pain relief was maintained up to 6 hours in 50%, 70%, 78%,
      and 81% of patients after these four doses. Only 25% of the patients achieved
      adequate pain relief with placebo. CONCLUSIONS: A population pharmacokinetic
      pharmacodynamic model for the analgesic efficacy of intramuscular ketorolac was
      derived. The simulated relationship between dose, time, and percentage of
      patients with adequate pain relief suggested that 30 mg intramuscular ketorolac
      was the optimal initial dose for postoperative pain relief.

PMID- 8988065
TI  - The hypoalgesic effect of tramadol in relation to CYP2D6.
AB  - Tramadol inhibits norepinephrine reuptake, stimulates serotonin release, and acts
      with mu-opioid receptors by way of its metabolite (+)-M1. Formation of M1 seems
      to depend on the genetic polymorphic CYP2D6. The analgesic effect of 2 mg/kg
      tramadol was evaluated in 15 extensive and 12 poor metabolizers of sparteine in
      two parallel, randomized, double-blind, placebo-controlled crossover studies that
      used experimental pain models. In extensive metabolizers, tramadol increased
      pressure pain detection (p = 0.03) and tolerance (p = 0.06) thresholds, as well
      as thresholds for eliciting nociceptive reflexes, after single (p = 0.0002) and
      repeated (p = 0.06) stimulation of the sural nerve. Peak pain and pain area in
      the cold pressor test were reduced (p = 0.0006 and 0.0009). In poor metabolizers,
      only thresholds to pressure pain tolerance (p = 0.02) and nociceptive reflexes
      after single stimulation (p = 0.04) were increased and the reflex threshold was
      less increased in poor metabolizers than in extensive metabolizers (p = 0.02).
      The serum concentration of (+)-M1 2 to 10 hours after tramadol ranged from 10 to
      100 ng/L in extensive metabolizers, whereas in poor metabolizers serum
      concentrations of (+)-M1 were below or around the detection limit of 3 ng/ml. It
      is concluded that formation of (+)-M1 by way of CYP2D6 is important for the
      effect of tramadol on experimental pain.

PMID- 8988066
TI  - Multiple-dose pharmacokinetics of cefpirome in long-term hemodialysis with high
      flux membranes.
AB  - Cefpirome is a cephalosporin eliminated primarily by kidneys that requires dosage
      reduction in patients with renal failure. The pharmacokinetic parameters were
      studied in 10 patients with end-stage renal disease who were receiving
      hemodialysis. Repeated intravenous administration of 2 gm cefpirome three times a
      week resulted in trough levels of 12.2 +/- 5.4 micrograms/ml and peak serum
      concentrations of 99.6 +/- 82.1 micrograms/ml. After 3 1/2 hours of hemodialysis
      with polysulfone high-flux membranes, 62.3% +/- 23.3% of cefpirome was removed.
      The interdialytic half-life was 9.35 +/- 0.99 hours, and the intradialytic half
      life was 2.02 +/- 0.7 hours.

PMID- 8988067
TI  - Decrease of plasma and urinary oxidative metabolites of acetaminophen after
      consumption of watercress by human volunteers.
AB  - To investigate the effect of the consumption of watercress (Nasturtium officinale
      R. Br.), a cruciferous vegetable, on acetaminophen metabolism, the
      pharmacokinetics of acetaminophen and its metabolites were studied in a crossover
      trial of human volunteers. A single oral dose of acetaminophen (1 gm) was given
      10 hours after ingestion of watercress homogenates (50 gm). In comparison with
      acetaminophen only, the ingestion of watercress resulted in a significant
      reduction in the area under the plasma cysteine acetaminophen (Cys-acetaminophen)
      concentration-time curve and in the peak plasma Cys-acetaminophen concentration
      by 28% +/- 3% and by 21% +/- 4% (mean +/- SE; n = 7; p < 0.005), respectively.
      Correspondingly, the Cys-acetaminophen formation rate constant and Cys
      acetaminophen formation fraction were decreased by 55% +/- 9% and 52% +/- 7% (p <
      0.01), respectively. Consistent with the results obtained from the plasma, the
      total urinary excretion of Cys-acetaminophen in 24 hours was also reduced. A
      decrease of mercapturate acetaminophen, a Cys-acetaminophen metabolite, was also
      shown in the plasma and urine samples. However, the plasma pharmacokinetic
      processes and the urinary excretions of acetaminophen, acetaminophen glucuronide,
      and acetaminophen sulfate were not altered significantly by the watercress
      treatment. These results suggest that the consumption of watercress causes a
      decrease in the levels of oxidative metabolites of acetaminophen, probably due to
      inhibition of oxidative metabolism of this drug.

PMID- 8988068
TI  - Genotyping of S-mephenytoin 4'-hydroxylation in an extended Japanese population.
AB  - OBJECTIVE: To assess the genotype pattern of S-mephenytoin 4'-hydroxylation in an
      extended Japanese population. METHODS: One hundred eighty-six unrelated, healthy
      Japanese subjects were genotyped for S-mephenytoin 4'-hydroxylase (CYP2C19)
      according to a genotyping technique to identify the wild-type (wt) gene and two
      mutations, CYP2C19m1 in exon 5 and CYP2C19m2 in exon 4. Fourty-six of the 186
      subjects genotyped were phenotyped with racemic mephenytoin using the
      conventional 8-hour urine analysis of 4'-hydroxymephenytoin. RESULTS: The
      frequency of poor metabolizers by the genotyping analysis was 18.8% (35 of the
      186 subjects), consisting of 12 homozygous for CYP2C19m1 (m1/m1), three
      homozygous for CYP2C19m2 (m2/m2), and 20 heterozygous for the two defects
      (m1/m2). Thus the allele frequencies of CYP2C19m1 and CYP2C19m2 were calculated
      to be 0.29 and 0.13 (107 and 46 of the total of 372 alleles), respectively. Among
      the 46 subjects phenotyped, seven were identified as the poor metabolizers, with
      a log10 urinary excretion of 4'-hydroxymephenytoin of < 0.3% of the racemic dose.
      These seven subjects were genotyped as the individuals with the m1/m1 (two),
      m1/m2 (four) or m2/m2 (one) allele combination, indicating a complete concordance
      between the phenotyping and genotyping tests. CONCLUSION: The present genotyping
      test confirmed that the frequency of CYP2C19 mutant gene m1 is about 2.2 times
      greater than another mutant gene, m2, among Japanese poor metabolizers. The
      genotyping of CYP2C19 discriminates between the two S-mephenytoin 4'
      hydroxylation phenotypes completely in the Japanese subjects.

PMID- 8988069
TI  - Abnormal desmopressin-induced forearm vasodilatation in patients with heart
      failure: dependence on nitric oxide synthase activity.
AB  - BACKGROUND: Peripheral vasodilatation in response to muscarinic agonists has been
      shown to be subnormal during heart failure. However, a more recent study
      suggested that the abnormal muscarinic-induced vasodilatation was not due to
      abnormal nitric oxide synthase activity. This study was designed to show that
      nitric oxide synthase contributes to desmopressin-induced forearm vasodilatation
      and to determine whether vasodilatation mediated by nitric oxide synthase is
      abnormal during heart failure. METHODS: Desmopressin (10, 50, and 100 ng/min) was
      infused into the brachial artery of 10 healthy subjects and eight patients with
      heart failure, and forearm blood flow was measured by venous occlusion
      plethsymography. Desmopressin responses were then recorded during inhibition of
      nitric oxide synthase with L-monomethylarginine or after aspirin. RESULTS: In
      healthy subjects, desmopressin caused a significant (p < 0.001) dose-dependent
      increase in forearm blood flow of 0.9 +/- 0.6, 4.0 +/- 2.6, and 7.9 +/- 2.6
      ml/min/dl, respectively. Desmopressin responses in heart failure of 0.8 +/- 0.6,
      1.7 +/- 1.4, and 3.1 +/- 1.0 ml/min/dl were significantly less (p < 0.001) than
      normal. L-Monomethylarginine reduced desmopressin responses in normal subjects (p
      < 0.01), and this inhibitory effect was significantly (p < 0.01) greater than in
      patients with heart failure. Aspirin did not affect desmopressin-induced
      vasodilatation. CONCLUSION: Nitric oxide synthase contributes to desmopressin
      induced forearm vasodilatation. In response to desmopressin, patients with heart
      failure have subnormal vasodilatation mediated through nitric oxide synthase.

PMID- 8988070
TI  - A comparison of nebulized budesonide with oral prednisolone in the treatment of
      exacerbations of obstructive pulmonary disease.
AB  - Nebulized corticosteroids in acute bronchospasm may offer topical anti
      inflammatory activity while minimizing undesirable systemic effects. We compared
      the side-effect profile of nebulized budesonide (2 mg twice daily) with that of
      oral prednisolone (30 mg once daily) in a randomized parallel-group study of 19
      adults with severe acute airway obstruction. Over the 5 days of the study,
      baseline forced expiratory volume in 1 second (FEV1) increased from 1.8 (95%
      confidence interval [CI], 0.7) to 2.1 (95% CI, 0.7) L in the group that received
      oral corticosteroids compared with 1.9 (95% CI, 0.7) to 2.0 (95% CI, 0.7) L in
      the group that received nebulized corticosteroid. All biochemical variables were
      similar at day 1. Comparison of budesonide treatment with prednisolone on day 5
      showed that urinary corticosteroid metabolites were significantly higher (2012
      [95% CI, 812] compared with 1079 [95% CI, 346] mg/24 hr [p < 0.05]), urinary
      androgen metabolites were not different, serum osteocalcin was elevated (2.3 [95%
      CI, 1.4] compared with 0.6 [95% CI, 0.6] ng/ml [p < 0.05]), and 24-hour urinary
      calcium to creatinine ratios were lower (0.28 [95% CI, 0.1] compared with 0.53
      [95% CI, 0.2]), whereas urinary hydroxyproline to creatinine ratios were similar.
      The biochemical markers associated with corticosteroid side effects improve in
      patients treated with nebulized corticosteroids compared with patients who
      receive conventional treatment.

PMID- 8988071
TI  - The effect of ephedrine plus caffeine on smoking cessation and postcessation
      weight gain.
AB  - OBJECTIVES: To evaluate the efficacy of a combination of ephedrine and caffeine
      on smoking cessation rates, postcessation weight gain, and withdrawal symptoms
      and to examine changes in glycosylated hemoglobin (HbA1c) after smoking
      cessation. METHODS: This randomized double-blind placebo-controlled study with a
      1-year follow-up period was carried out at the Department of Pulmonary Medicine
      in Denmark. Study subjects were 225 heavy smokers who wanted to quit smoking
      without gaining weight. Two-thirds of the subjects were randomized to receive 20
      mg ephedrine plus 200 mg caffeine three times a day; one-third of the subjects
      received placebo treatment. The dosage was gradually decreased from week 12 to
      discontinuation at week 39. Group support and control were performed at entry and
      after 1, 3, 6, 12, 26, 39, and 52 weeks. Main outcome measures were (1) self
      reported abstinence with validation by carbon monoxide in expired air and serum
      cotinine and (2) weight gain. RESULTS: The success rates after 1 year were 17% in
      the group treated with ephedrine plus caffeine and 16% in the group treated with
      placebo; the success rates were not significantly different at any time. The
      success rates for the four counseling physicians varied between 7% and 27% after
      1 year (p < 0.05). The weight gain was significantly lower in the ephedrine plus
      caffeine-treated group during the first 12 weeks, but weight gains were similar
      after 1 year. No differences in the smoking withdrawal symptoms could be observed
      between the treatment groups. HbA1c was lower 6 weeks and 1 year after smoking
      cessation (p < 0.05). CONCLUSIONS: We found an effect of this combination of
      ephedrine and caffeine on weight gain during the first 12 weeks, but we found no
      effect on the success rates or craving for cigarettes.

PMID- 8988073
TI  - Low frequency of dextromethorphan O-demethylation deficiency in a Chinese
      population.

PMID- 8988072
TI  - Multiple-dose pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an
      inhibitor of HMG-CoA reductase, in healthy subjects.
AB  - This study examined the pharmacokinetics, pharmacodynamics, and safety of
      atorvastatin, an investigational inhibitor of 3-hydroxy-3-methylglutaryl coenzyme
      A (HMG-CoA) reductase, in 50 healthy subjects by means of a randomized, double
      blind parallel-group design. Volunteers received rising single and multiple doses
      of 0.5 to 80 mg/day atorvastatin (40 subjects) or placebo (10 subjects). The drug
      was administered once or twice daily for 14 days. Atorvastatin was well tolerated
      by healthy subjects. The most common adverse events reported after atorvastatin
      headache and nausea-occurred as frequently after placebo. Atorvastatin peak
      concentration and area under the plasma concentration-time curve (AUC) values
      increased more than proportionally with atorvastatin dose after both single and
      multiple drug doses. The extent of atorvastatin absorption (AUC) was similar
      after once- or twice-daily drug administration. Steady-state drug concentrations
      were achieved by the third day of drug dosing. Mean elimination half-life values
      ranged from 11 to 24 hours. Atorvastatin accumulation was approximately 1.5- and
      3.0-fold after once- and twice-daily administration, respectively. Atorvastatin
      produced dose-related reductions in total cholesterol and low-density lipoprotein
      cholesterol that were similar after once- and twice-daily drug administration.
      Reductions in mean total cholesterol and low-density lipoprotein cholesterol
      values ranged from 13% and 22% (2.5 mg/day) to 45% and 58% (80 mg/day),
      respectively (p < or = 0.0013 in comparison with placebo and with baseline over
      this dose range). In summary, atorvastatin doses of up to 80 mg/day were well
      tolerated and had significant cholesterol-lowering effects.

PMID- 8988074
TI  - Continuous intraoperative electromyographic monitoring of cranial nerves during
      resection of fourth ventricular tumors in children.
AB  - The authors reviewed the results of continuous intraoperative electromyographic
      (EMG) monitoring of muscles innervated by cranial nerves in 17 children whose
      preoperative imaging studies showed compression or infiltration of the fourth
      ventricular floor by tumor to determine how intraoperative EMG activity
      correlated with postoperative cranial nerve morbidity. Bilateral lateral rectus
      (sixth) and facial (seventh) nerve musculatures were monitored in all children.
      Cranial nerve function was documented immediately postoperatively and at 1 year.
      Of the 68 nerves monitored, nine new neuropathies occurred in six children (sixth
      nerve in four children and seventh nerve in five). In five new neuropathies,
      intraoperative EMG activity could be correlated in one of four sixth nerve
      injuries and four of five seventh nerve injuries. Electromyographic activity
      could not be correlated in four children with new neuropathies. Of 59 cranial
      nerves monitored that remained unchanged, 47 had no EMG activity. Twelve cranial
      nerves (three sixth nerves and nine seventh nerves) had EMG activity but no
      deficit. Of four children with lateral rectus EMG activity, three had new seventh
      nerve injuries. Lateral rectus EMG activity did not predict postoperative
      abducens injury. The absence of lateral rectus EMG activity did not assure
      preserved abducens function postoperatively. Likely because of the close
      apposition of the intrapontine facial nerve to the abducens nucleus, lateral
      rectus EMG activity was highly predictive of seventh nerve injury. Although
      facial muscle EMG activity was not an absolute predictor of postoperative facial
      nerve dysfunction, the presence of facial muscle EMG activity was associated
      statistically with postoperative facial paresis. The absence of facial muscle EMG
      activity was rarely associated with facial nerve injury. The authors speculate
      that EMG activity in the facial muscles may have provided important
      intraoperative information to the surgeon so as to avoid facial nerve injury.

PMID- 8988075
TI  - Third ventricle colloid cysts: a consecutive 12-year series.
AB  - A continuous follow-up review of colloid cysts including aspects of natural
      history and evaluation of treatment options is necessary to optimize individual
      treatment. Thirty-seven consecutive patients with colloid cyst of the third
      ventricle seen at Karolinska Hospital between 1984 and 1995 were reviewed. Five
      patients were admitted in a comatose state, and two died despite emergency
      ventriculostomy. Three had recurrent cysts following previous aspiration
      procedure. During the study period, patients underwent a total of 10
      ventriculostomies, 10 aspirations, 26 microsurgical operations, and two shunt
      operations. Twenty-four of 26 microsurgical operations were transcallosal and two
      were transcortical. Twenty-four operations (22 transcallosal and two transfrontal
      approaches) without permanent morbidity were performed by four surgeons.
      Transient memory deficit from forniceal traction was noted in 26%. The remaining
      two transcallosal operations, which led to permanent morbidity or mortality, were
      performed by two different surgeons. Aspiration of cysts performed by four
      different surgeons carried a 40% risk of transient memory deficit (10% permanent)
      and an 80% recurrence rate. One patient was found to be cured on radiological
      studies obtained at the 5-year follow-up review. Seven cysts were followed by
      means of radiological studies with no treatment for 6 to 37 months. Five of these
      cysts grew, indicating that younger patients with colloid cysts will probably
      need surgical treatment. The main causes of unfavorable results were: 1) failure
      to investigate symptoms that proved fatal; 2) subtotal resection; and 3) surgical
      complications. Transcallosal microsurgery produced excellent results when
      performed by experienced surgeons. A colloid cyst of the foramen of Monro is a
      disease that should be detected before permanent neurological damage has
      occurred. Permanent morbidity or mortality should not be accepted in modern
      series of third ventricle colloid cysts.

PMID- 8988076
TI  - Medulloblastoma: is the 5-year survival rate improving? A review of 80 cases from
      a single institution.
AB  - A series of 80 cases of medulloblastomas in children undergoing operation and
      postoperatively followed between 1980 and 1990 at Great Ormond Street Hospital
      for Children (GOSH) has been reviewed and compared to an earlier series reported
      from the same institution by McIntosh. The overall 5-year survival rate for the
      present series was 50%, although three patients died after surviving 5 years. The
      operative mortality rate was 5%. Survival analysis revealed that the presence or
      absence of spinal metastases and the necessity for some form of cerebrospinal
      fluid diversion within 30 days of the operation independently significantly
      affected survival in this series. Those patients with no spinal metastasis and
      total tumor removal had a 5-year survival rate of 73%, making this the most
      favorable subgroup in the series. Patient age and gender, duration of symptoms,
      Chang T stages, tumor volume, extent of resection, and postoperative chemotherapy
      were not significant variables. Although these results are better than those
      reported in the earlier GOSH series, they are not significantly different from
      the results of the second 5-year cohort of patients described in that article.
      Radiotherapy remains the greatest advance in treatment, although it is hoped that
      further improvement will result from the various chemotherapy protocols now being
      studied and from increasing knowledge of the biological behavior of these tumors.

PMID- 8988077
TI  - Utility of relative cerebral blood volume mapping derived from perfusion magnetic
      resonance imaging in the routine follow up of brain tumors.
AB  - It was recently demonstrated that imaging of brain tumors by relative cerebral
      blood volume (CBV) maps reconstructed from dynamic magnetic resonance (MR) data
      provide similar diagnostic information compared to positron emission tomography
      (PET) or 201Tl single-photon emission computerized tomography (201Tl-SPECT)
      scans. The authors used relative CBV mapping for routine follow-up evaluation of
      patients with brain tumors and compared its sensitivity to diagnostic MR imaging,
      201Tl-SPECT and clinical assessment. Fifty-nine patients were prospectively
      followed using 191 concomitant studies of dual section relative CBV maps, MR
      imaging, 201Tl-SPECT, and neurological evaluations. Studies were repeated every 2
      to 3 months (median three evaluations/patient). The relative CBV maps were graded
      as relative CBV 0 to 4, where Grades 3 and 4 are indicative of proliferating
      tumors (four = rapid leak). There were 44 high-grade and 15 low-grade tumors
      followed during treatment. During the follow-up period a change in relative CBV
      grade was observed in 56% of the patients, revealing an increasing grade in 72%
      of them. The rapid leak phenomenon was detected in 35% of all studies and in 81%
      of those with a worsening relative CBV grade. Tumor progression was detected
      earlier by relative CBV maps as follows: earlier than MR imaging in 32% of the
      studies (earlier by a median of 4.5 months; p < 0.01); earlier than 201Tl-SPECT
      in 63% (median 4.5 months; p < 0.01), and earlier than clinical assessment in 55%
      (median 6 months; p < 0.01). In 82% of studies with positive MR imaging but
      negative 201Tl-SPECT, the lesions were smaller than 1.5 cm. The relative CBV maps
      clearly delineated the appearance of rapid leak in these lesions. Routine use of
      relative CBV maps that can be implemented on any high-field MR unit and added to
      the regular MR evaluation provides useful functional information in patients with
      brain tumors. When used as an adjunct follow-up evaluation it proved more
      sensitive than the other modalities for early prediction of tumor growth. It is
      very sensitive to small regional changes, unlike functional imaging such as PET
      or SPECT scans. Based on previous experience with 76 regional CBV studies, the
      authors conclude that regional CBV mapping correlates with active tumor and it
      may separate enhancing scar and radiation injury from infiltrative tumor. A new
      effect named the rapid leak phenomenon was also observed; this phenomenon, as
      identified on the regional CBV maps, correlates with high malignancy.

PMID- 8988078
TI  - Lack of specificity in electrophysiological identification of lower sacral roots
      during selective dorsal rhizotomy.
AB  - The authors investigated the efficacy of anal sphincter electromyography (EMG) in
      identifying the lower sacral roots during selective dorsal rhizotomy. In nine
      children undergoing selective dorsal rhizotomy for cerebral palsy (CP)
      spasticity, direct electrical stimulation of the L1-S5 dorsal and ventral roots
      was performed while monitoring EMG responses from the anal sphincter and lower
      extremity muscles. Anal sphincter activation was seen with stimulation of
      lumbosacral roots at many levels. Stimulation of dorsal and ventral roots gave
      anal sphincter EMG responses in 100% of the dorsal and ventral roots from L-4 and
      caudally. Only at the L-1 level did a minority of nerve roots have anal sphincter
      response to stimulation. Patterns of extremity muscle and sphincter activation
      specific to the S3-5 roots, namely anal sphincter activation without activation
      of other muscle groups, were found in only five (22%) of 23 roots stimulated. The
      pattern of stimulation responses in the majority of S3-5 roots indicated that the
      pathophysiology of lower-extremity spasticity in CP may involve the anal
      sphincter and does not spare the lower sacral roots. Thus, this study indicates
      that electrophysiological mapping alone, without anatomical identification,
      cannot be used to identify the lower sacral roots during selective dorsal
      rhizotomy for CP spasticity, and it proposes a model for investigation of
      associated bowel and bladder symptoms.

PMID- 8988079
TI  - Selective dorsal rhizotomy and rates of orthopedic surgery in children with
      spastic cerebral palsy.
AB  - If the spasticity of cerebral palsy (CP) is reduced in children at a young age by
      selective dorsal rhizotomy, the incidence of lower-extremity deformities
      requiring orthopedic surgery may be reduced; however, this has never been
      investigated in detail. The authors examined the effects of selective dorsal
      rhizotomy on rates of lower-extremity orthopedic surgery in 178 children with CP.
      Age at selective dorsal rhizotomy ranged from 2 to 19.3 years (mean 5.5 years)
      with follow-up intervals ranging from 24 to 70 months (mean 44 months). Spastic
      CP was classified as quadriplegia (33%), diplegia (65%), and hemiplegia (2%). To
      assess the effects of early versus late rhizotomy on rates of orthopedic surgery,
      patients were grouped as follows: Group I underwent rhizotomy between 2 and 4
      years of age (54 patients), and Group II underwent rhizotomy between 5 and 19
      years of age (124 patients). Comparison of Kaplan-Meier plots of lifetime
      orthopedic surgery rates revealed that Group II underwent orthopedic surgery at a
      higher rate than Group I (p = 0.037). Analysis by procedure type revealed higher
      orthopedic surgery rates in Group II than Group I for heel cord releases (p =
      0.0025), adductor releases (p = 0.018), and hamstring releases (p = 0.02).
      Orthopedic surgery rates were no higher for Group II compared to Group I for
      ankle/foot operations (p = 0.023), femoral osteotomy (p = 0.25), iliopsoas
      releases (p = 0.35), and "other" operations (p = 0.013). The data indicate that
      early rhizotomy reduces the need for orthopedic surgery for heel cord, hamstring,
      and adductor releases.

PMID- 8988080
TI  - Pathogenesis of Chiari malformation: a morphometric study of the posterior
      cranial fossa.
AB  - To investigate overcrowding in the posterior cranial fossa as the pathogenesis of
      adult-type Chiari malformation, the authors studied the morphology of the
      brainstem and cerebellum within the posterior cranial fossa (neural structures
      consisting of the midbrain, pons, cerebellum, and medulla oblongata) as well as
      the base of the skull while taking into consideration their embryological
      development. Thirty patients with Chiari malformation and 50 normal control
      subjects were prospectively studied using neuroimaging. To estimate overcrowding,
      the authors used a "volume ratio" in which volume of the posterior fossa brain
      (consisting of the midbrain, pons, cerebellum, and medulla oblongata within the
      posterior cranial fossa) was placed in a ratio with the volume of the posterior
      fossa cranium encircled by bony and tentorial structures. Compared to the control
      group, in the Chiari group there was a significantly larger volume ratio, the two
      occipital enchondral parts (the exocciput and supraocciput) were significantly
      smaller, and the tentorium was pronouncedly steeper. There was no significant
      difference in the posterior fossa brain volume or in the axial lengths of the
      hindbrain (the brainstem and cerebellum). In six patients with basilar
      invagination the medulla oblongata was herniated, all three occipital enchondral
      parts (the basiocciput, exocciput, and supraocciput) were significantly smaller
      than in the control group, and the volume ratio was significantly larger than
      that in the Chiari group without basilar invagination. These results suggest that
      in adult-type Chiari malformation an underdeveloped occipital bone, possibly due
      to underdevelopment of the occipital somite originating from the paraxial
      mesoderm, induces overcrowding in the posterior cranial fossa, which contains the
      normally developed hindbrain. Basilar invagination is associated with a more
      severe downward herniation of the hindbrain due to the more severely
      underdeveloped occipital enchondrium, which further exacerbates overcrowding of
      the posterior cranial fossa.

PMID- 8988081
TI  - Selection criteria and outcome of operative approaches for thoracolumbar burst
      fractures with and without neurological deficit.
AB  - Criteria for choosing operative techniques for the treatment of thoracolumbar
      burst fractures remain disputed, particularly in neurologically intact patients.
      A retrospective study of 25 patients with thoracolumbar burst fractures was
      performed to assess fracture characteristics, operative approaches, fixation,
      radiographic results, and neurological, functional, and pain outcomes. Anterior
      corpectomy, allograft strut, and plate fixation were performed in 14 patients
      with or without neurological deficit when vertebral compression or canal
      encroachment was at least 40% or kyphosis was 15 degrees or more with a stable
      posterior column. In nine cases, an anterior operation and a posterior segmental
      fixation were combined for similar deformity and three-column instability.
      Posterior transpedicular decompression, fixation, and fusion were used primarily
      for two symptomatic patients with less than 40% encroachment and at most 40%
      compression. Overall, 21 patients (84%) were walking and 18 (72%) were continent
      at follow-up evaluation (mean 16.3 months) versus eight (32%) and 11 (44%) at
      presentation, respectively. Preoperatively, 17 patients experienced neurological
      deficit; 16 improved and 12 increased one Frankel grade. No patient deteriorated.
      Prior employment or activity level was resumed by 19 patients (76%) and only four
      patients professed incapacity. Pain was eliminated after 18 procedures (72%), all
      anterior or combined approaches. Restoration of anatomical alignment (< 5
      degrees) was achieved in 19 cases. No anterior construct failed and only one
      patient treated posteriorly had postoperative kyphosis progression. Operative
      morbidity occurred in three cases (12%). Satisfactory neurological and functional
      outcomes were achieved in a majority of patients with thoracolumbar burst
      fractures after correction of canal compromise, middle column compression, and
      attendant deformity. These results indicate that anterior decompression and a
      weight-bearing strut graft are critical to clinical success in patients with
      significant vertebral destruction.

PMID- 8988082
TI  - Outcome analysis for adults with spondylolisthesis treated with posterolateral
      fusion and transpedicular screw fixation.
AB  - The outcomes of 52 adult patients with symptomatic low-grade spondylolisthesis
      treated with autologous posterolateral arthrodesis and pedicle screw fixation
      were retrospectively reviewed. Although a 90% rate of successful fusion was
      obtained using this technique, only 60% of patients were considered to have good
      outcomes. Treatment failures consisted mostly of back pain and were not predicted
      by preoperative symptoms. Compensation claims and smoking had very significant
      adverse impacts on both employment and pain results despite high fusion rates,
      particularly in patients under the age of 55 years. Overall, patients who
      required more than one operation demonstrated poor outcomes compared to those who
      only needed one. However, patients with at least two prior operations or
      preoperative pseudoarthrosis fared particularly poorly, whereas those who had
      undergone only one prior surgery and had no attendant compensation issue reported
      good results. A trend toward poor outcome was observed in patients with
      postlaminectomy spondylolisthesis, versus those with isthmic or degenerative
      etiologies. Gender did not exert an impact on outcome. The authors conclude that
      autologous posterolateral arthrodesis combined with pedicle screw fixation
      resulted in a high fusion rate, and contributed to successful outcomes in the
      treatment of certain subgroups of adults with spondylolisthesis. In the absence
      of other risk factors, patients may obtain significant benefit from surgery
      despite older age and a single failed operation. Careful patient selection
      appears critical in predicting the maximum benefit from this technique.

PMID- 8988083
TI  - Modified open-door cervical expansive laminoplasty for spondylotic myelopathy:
      operative technique, outcome, and predictors for gait improvement.
AB  - Twenty-five patients underwent an expansive cervical laminoplasty for
      nontraumatic cervical spondylosis with myelopathy during the period from June
      1990 to November 1994, and all had a minimum of 18 months of follow-up review.
      The open-door laminoplasty procedure presently reported consisted of the same
      approach evaluated by Hirabayashi in 1977, except that the authors of this report
      used three rib allografts to anchor the "open door," rather than spinous process
      sutures or autologous bone grafts. Posterior foraminotomies and decompression
      were performed in patients with clinical radiculopathy and radiographic evidence
      of foraminal stenosis. Preoperatively, gait disturbance was present in all
      patients. All 25 patients (100%) had long-tract signs on presentation.
      Nondermatomal upper-extremity symptoms (numbness, tingling, weakness, and pain)
      were quite common in this group of patients. Bowel, bladder, and/or sexual
      dysfunction was found in 13 (52%) of 25 patients. Preoperative radiographic
      studies showed a mean midline anteroposterior diameter spinal canal/vertebral
      body (SC/VB) ratio of 0.623 and a mean compression ratio (sagittal/lateral
      diameter ratio x 100%) of 37%. This procedure was quite successful in relieving
      preoperative symptoms and few complications occurred. Gait disturbance was
      improved in 21 (84%) of 25 patients and hand numbness and tingling were improved
      in 13 (87%) of 15 patients. Bowel or bladder function improved in 10 (77%) of 13
      patients. Radiculopathy, when present, was alleviated in all four patients after
      the decompressive procedure. The postoperative SC/VB ratio, as measured by plain
      lateral radiographs and/or computerized tomography scans, was improved to 0.871,
      a 38% improvement. In a comparison with the preoperative SC/VB ratio using the
      two-tailed t-test, alpha was less than 0.001. The compression ratio improved to
      63% postoperatively, which yielded an alpha of less than 0.005 according to the
      two-tailed t-test. Only one postoperative complication, an anterior scalene
      syndrome, was encountered. Various predictors of surgical outcome based on gait
      improvement were evaluated. Age greater than 60 years at the time of
      presentation, duration of symptoms more than 18 months prior to surgery,
      preoperative bowel or bladder dysfunction, and lower-extremity dysfunction were
      found to be associated with poorer surgical outcome. Even when these conditions
      were present, gait improvement was noted in at least 70% of the patients.

PMID- 8988084
TI  - Diagnosis of root avulsions in traumatic brachial plexus injuries: value of
      computerized tomography myelography and magnetic resonance imaging.
AB  - Surgical management and prognosis of traction injuries of the brachial plexus
      depend on the accurate diagnosis of root avulsion from the spinal cord.
      Myelography, computerized tomography (CT) myelography, and recently magnetic
      resonance (MR) imaging have become the main radiological methods for preoperative
      diagnosis of cervical root avulsions. Most of the previous studies on the
      accuracy of CT myelography and MR imaging studies have correlated the
      radiological findings with the extraspinal surgical findings at brachial plexus
      surgery. Surgical experience shows that in many cases extraspinal findings
      diverge from intradural determinations. Consequently, only correlation with the
      intradural surgical findings will allow assessment of the factual accuracy of CT
      myelography and MR imaging studies. In a prospective study, 135 cervical roots
      (C5-8) were evaluated by CT myelography and/or MR imaging and further explored
      intradurally via a hemilaminectomy. The accuracy of the preoperative CT
      myelography-based diagnosis in relation to the intraoperative findings was 85%.
      On the other hand, MR imaging demonstrated an accuracy of only 52%. The most
      common reasons for false-positive or false-negative findings were: 1) partial
      rootlet avulsion; 2) intradural fibrosis; and 3) dural cystic lesions.
      Computerized tomography myelography scans using 1- to 3-mm axial slices prove to
      be the most reliable method to evaluate preoperatively the presence of complete
      or partial root avulsion in traumatic brachial plexus injuries. Because
      extradural judgment of cervical root avulsion can be unreliable, accurate
      assessment of intraspinal root avulsion enormously simplifies the decision
      concerning the choice of donor nerves for transplantation and/or neurotization
      during brachial plexus surgery.

PMID- 8988085
TI  - Toward an agreement on terminology of nuclear and subnuclear divisions of the
      motor thalamus.
AB  - The nomenclature most commonly applied to the motor-related nuclei of the human
      thalamus differs substantially from that applied to the thalamus of other
      primates, from which most knowledge of input-output connections is derived.
      Knowledge of these connections in the human is a prerequisite for stereotactic
      neurosurgical approaches designed to alleviate movement disorders by the
      placement of lesions in specific nuclei. Transfer to humans of connectional
      information derived from experimental studies in nonhuman primates requires
      agreement about the equivalence of nuclei in the different species, and dialogue
      between experimentalists and neurosurgeons would be facilitated by the use of a
      common nomenclature. In this review, the authors compare the different
      nomenclatures and review the cyto- and chemoarchitecture of the nuclei in the
      anterolateral aspect of the ventral nuclear mass in humans and monkeys, suggest
      which nuclei are equivalent, and propose a common terminology. On this basis, it
      is possible to identify the nuclei of the human motor thalamus that transfer
      information from the substantia nigra, globus pallidus, cerebellum, and
      proprioceptive components of the medial lemniscus to prefrontal, premotor, motor,
      and somatosensory areas of the cerebral cortex. It also becomes possible to
      suggest the principal functional systems involved in stereotactically guided
      thalamotomies and the functional basis of the symptoms observed following
      ischemic lesions in different parts of the human thalamus.

PMID- 8988086
TI  - Utilization of type I collagen gel, demineralized bone matrix, and bone
      morphogenetic protein-2 to enhance autologous bone lumbar spinal fusion.
AB  - Autologous bone grafts are currently considered "gold standard" material for
      achieving long-term spinal arthrodesis. The present study was performed to
      determine whether demineralized bone matrix (DBM), type I collagen gels, or bone
      morphogenetic protein-2 (BMP-2) can improve autologous bone spinal fusions. Using
      a unilateral decompression-contralateral fusion technique in dogs, each of these
      materials was added to an autologous bone graft. Volumetric analysis,
      histological analysis, and biomechanical testing were performed to assess the
      effectiveness of each material. The DBM had an inhibitory effect on solid bone
      fusion of the spine, whereas the type I collagen gels improved the bony interface
      between the graft and the host spine. The BMP-2 strongly enhanced the amount of
      bone deposition at the fusion site and increased the number of intervertebral
      levels that were solidly fused. This study strongly supports the use of BMP-2 as
      an additive to autologous bone grafts in spine stabilization.

PMID- 8988087
TI  - Specific repression of the preproendothelin-1 gene in intracranial arteriovenous
      malformations.
AB  - Cerebrovascular arteriovenous malformations (AVMs) display abnormal vascular
      development and dysautoregulation of blood flow. Genetic mechanisms that
      contribute to the pathogenesis and phenotype of cerebral AVMs are unknown. As a
      first step in understanding the pathophysiology of AVMs, the authors investigated
      the hypothesis that endothelial dysfunction-specifically, deregulation of
      endothelin-1 (ET-1) secretion-contributes to the abnormal vascular phenotype and
      the lack of hemodynamic autoregulation elaborated by these lesions. Endothelin-1
      peptide and preproendothelin-1 (ppET1) messenger RNA were not detected in the
      intranidal vasculature of all 17 patients with AVMs studied, but were prominently
      expressed in human control subjects with normal cerebrovasculature (p < 0.01).
      Although AVM vasculature lacked ET-1, its expression was prominent in vasculature
      distant from these lesions, suggesting local repression of the ppET-1 gene. Local
      repression of ET-1 was specific to AVMs; ET-1 in vascular malformations of
      patients with Sturge-Weber disease was actually elevated compared to normal
      controls (p < 0.01). Repression of the ppET-1 gene was an intrinsic phenotype of
      AVM endothelial cells and was not due to factors in the AVM microenvironment. The
      authors also showed that ETA receptor expression was low in AVM vasculature
      compared to normal controls. Together, these results demonstrate that the ppET-1
      gene is locally repressed in AVM lesions and suggest a role for abnormal ppET-1
      gene regulation in the pathogenesis and clinical sequelae of cerebral AVMs.

PMID- 8988088
TI  - Histological interaction of cultured endothelial cells and endovascular embolic
      materials coated with extracellular matrix.
AB  - This study was undertaken to evaluate the histological reaction of cultured
      endothelial cells to endovascular embolic materials in vitro. Endothelial cells
      were isolated and cultured from a canine carotid artery. Embolic materials
      (platinum microcoils, polyvinyl alcohol particles, silicon balloons, or silk
      threads), either in their normal state or after having been coated with type 1
      collagen, fibronectin, or laminin, were placed on endothelial cells and
      cocultured for 6, 12, and 24 hours and 2, 3, 7, 14, and 21 days. The cocultures
      were investigated histologically using a scanning electron microscope.
      Endothelial cells were not found on any uncoated embolic materials, even at 21
      days. On the materials coated with fibronectin or laminin, endothelial cells
      began to proliferate in 7 days, covering the materials extensively in 14 days. On
      the other hand, endothelial cells began to proliferate on the collagen-coated
      materials in 3 days, covering them extensively in 7 days and reaching confluence
      with a cobblestone pattern in 21 days. The densities of endothelial cells on
      collagen-coated materials were much higher than those observed on the materials
      coated with other extracellular matrices. Future advantages of the clinical use
      of collagen-coated embolic materials in interventional treatment are discussed.

PMID- 8988089
TI  - Progesterone and estrogen receptors in meningiomas: prognostic considerations.
AB  - Meningiomas often contain steroid hormone receptors, but the correlation of
      receptor presence with patient outcome or mitotic index is unclear. Intracranial
      meningiomas from 70 patients (27 males and 43 females, mean age 52.9 + 1.7 years
      [mean +/- standard error of the mean], range 15-78 years) were evaluated
      immunocytochemically for female sex hormone receptors using specific monoclonal
      antibodies. Prognostic correlations were determined using statistical analyses
      that included clinical and histological variables. Twenty-eight tumors were
      benign, 27 had atypical features, and 15 were malignant. Thirty tumors were
      meningotheliomatous, 11 were fibroblastic, 28 were transitional, and one was
      secretory. Twenty-nine of the 70 primary tumors recurred (mean interval to
      recurrence 50.1 +/- 10 months). The mean progression-free follow-up period for
      patients without recurrence was 82.1 +/- 7.7 months. Nuclear staining for the
      progesterone receptor (PR) was found in 58 cases (83%) and PR status was scored
      as 0 (0% nuclei positive), 1 (< 1%), 2 (1-9%), 3 (10-49%), or 4 (> 50%). Only six
      tumors (8.6%) contained nuclear estrogen receptor (ER) staining, which was
      limited to a small number of nuclei (< 1%). Fisher's exact test (two-tailed)
      showed an inverse correlation between tumor grade and PR staining score (p < or =
      0.001), with 96% of benign and 40% of malignant meningiomas containing PR
      positive nuclei. No correlation between age or histological subtype and PR score
      was detected. Meningiomas from female patients had more PRs (p < or = 0.05).
      Analysis of variance revealed that the mitotic index (total counts of mitoses per
      10 high-power fields) for tumors with 0 PR staining (18 +/- 4.4) was higher (p <
      or = 0.0001) than for those with PR scores of 1 to 4 (4.3 +/- 1.9, 5.1 +/- 2, 2.2
      +/- 0.8, and 1.7 +/- 0.9, respectively). Univariate analysis indicated that the
      absence of PR, high mitotic index, and higher tumor grade were significant
      factors for shorter disease-free intervals. Multivariate analysis showed that a
      three-factor interaction model, with a PR score of 0, mitotic index greater than
      6, and malignant tumor grade, was a highly significant predictor (p < or =
      0.0001) for worse outcome in patients harboring meningiomas. These data indicate
      that the presence of PRs, even in a small number of tumor cells, is a favorable
      prognostic factor for meningiomas.

PMID- 8988090
TI  - Analysis of proliferation markers and p53 expression in gliomas of astrocytic
      origin: relationships and prognostic value.
AB  - Consecutive paraffin sections of 105 astrocytomas and 15 oligoastrocytomas were
      examined for expression of p53, MIB-1 (Ki-67), and proliferating cell nuclear
      antigen (PCNA). The tumors had been examined previously for genetic abnormalities
      and by flow cytometry. Regardless of the tumor's stage and grade and the
      patient's age and gender, p53 expression was found in 40% of tumors. Although p53
      expression was associated with a loss on chromosome 17p and was more frequent in
      aneuploid tumors, it had no association with survival time. The MIB-1 and PCNA
      labeling indices increased with increasing tumor grade but showed no association
      with other clinicopathological parameters. In individual tumors, there was poor
      concordance between any of the variables (MIB-1, PCNA, and p53). Results for p53
      and MIB-1 were similar for both astrocytomas and oligoastrocytomas. The MIB-1 and
      PCNA values appeared to have prognostic utility in univariate analysis but not
      after adjusting for patient age and tumor grade. The poor concordance between MIB
      1 and PCNA in individual tumors indicates that any one means of assessing
      proliferative potential in gliomas may not be reliable.

PMID- 8988091
TI  - Effect of hemodilution with diaspirin cross-linked hemoglobin on intracranial
      pressure, cerebral perfusion pressure, and fluid requirements after head injury
      and shock.
AB  - Hemodilution has been shown to increase cerebral blood flow (CBF) and reduce
      lesion volume in models of occlusive cerebral ischemia, but it has not been
      evaluated in the setting of head trauma and shock in which ischemia is thought to
      play a role in the evolution of secondary injury. In a porcine model of brain
      injury and shock the authors compared hemodilution with diaspirin cross-linked
      hemoglobin (DCLHb) to a standard resuscitation regimen using Ringer's lactate
      solution and shed blood. After creation of a cryogenic brain injury followed by
      hemorrhage, the animals received a bolus of either 4 ml/kg of Ringer's lactate
      solution (Group 1, six animals) or DCLHb (Group 2, six animals), followed by
      infusion of Ringer's lactate solution to restore mean arterial pressure (MAP) to
      baseline. Group 1 received shed blood 1 hour after hemorrhage (R1) in the form of
      packed red blood cells. Group 2 received shed blood only for an Hb count of less
      than 5 g/dl. The animals were monitored for 24 hours. At R1, Group 2 had a
      significantly greater cerebral perfusion pressure ([CPP] 88 +/- 5.7 vs. 68 +/-
      2.4 mm Hg, p < 0.05). By 3 hours after hemorrhage (R3) Group 2 had a
      significantly lower Hb concentration (8.5 +/- 0.4 vs. 12.1 +/- 0.3 g/dl, p <
      0.05) and a significantly lower intracranial pressure ([ICP] 9 +/- 0.8 vs. 14 +/-
      0.6 mm Hg, p < 0.05). The total 24-hour fluid requirement was significantly less
      in Group 2 (10,654 +/- 505 ml vs. 15,542 +/- 1094 ml, p < 0.05) There was no
      difference between the groups regarding levels of regional CBF in the injured
      hemisphere. Cerebral O2 delivery was not significantly different between groups
      at any time. Lesion volume as determined at postmortem examination was not
      significantly different between the groups. The increased MAP and CPP and lower
      ICP observed in the Group 2 animals indicate that hemodilution with DCLHb may be
      beneficial in the treatment of head injury and shock.

PMID- 8988092
TI  - Activation of complement by tissue plasminogen activator, but not acute cerebral
      ischemia, in a rabbit model of thromboembolic stroke.
AB  - Although complement activation is associated with tissue injury during
      inflammatory and ischemic states, complement activation in states of acute
      cerebral ischemia before and after administration of tissue plasminogen activator
      (TPA) has not yet been examined and is the focus of this investigation. Twenty
      four New Zealand White rabbits weighing 3 to 3.5 kg were used for this study. Of
      these, 20 were subjected to intracranial autologous clot embolization via the
      internal carotid artery. Three hours postembolization, rabbits received an
      intravenous infusion of TPA (6.3 mg/kg, 20% bolus with the remainder infused over
      a 2-hour interval; 12 animals) or vehicle (eight animals). All animals were
      observed for a total of 7 or 8 hours postembolization. These two groups were
      compared to a cohort undergoing sham operation with subsequent TPA infusion (four
      animals). Plasma samples to quantify complement component C5 hemolytic activity
      (C5H5O) were obtained at the following time points: 30 minutes before and after
      clot embolization; 1 hour before and 1 hour after the initiation of therapy with
      TPA or vehicle and at the completion of the protocol; 7 to 8 hours after clot
      embolization. The C5 activation was not detected as the result of acute cerebral
      ischemia. However, animals receiving TPA with or without concomitant clot
      embolization exhibited C5 activation as assessed by a reduction in C5 hemolytic
      function, both 1 hour after initiation of TPA infusion (78.7 +/- 10.3% and 77.5
      +/- 9.9% of baseline value, respectively; mean +/- standard error of the mean
      [SEM]) and at the end of the protocol, 2 hours after the completion of the TPA
      infusion (72.5 +/- 8.8% and 53.3 +/- 8.1%, respectively; mean +/- SEM, p < 0.05,
      each group). This study supports the conclusion that TPA, but not acute cerebral
      ischemia, may activate the complement cascade in this rabbit model of
      thromboembolic stroke.

PMID- 8988093
TI  - Duraplasty with biosynthetic cellulose: an experimental study.
AB  - In the search for a new synthetic substitute for the dura mater, the authors
      conducted a research study using 32 mongrel dogs divided into three groups. Group
      I animals (21 dogs) underwent a right-sided parietooccipital craniotomy and
      substitution of two 1-cm pieces of dura mater by two different grafts: one piece
      of biosynthetic cellulose (50 mu thick) and one fragment of temporal fascia. The
      animals were observed for 30, 90, or 180 days. Group II animals (five dogs)
      underwent a somewhat larger craniotomy, removal of a 2-cm piece of dura mater,
      and lesioning of the cortex made by a thin sharp forceps, which caused bleeding
      that was controlled by application of a thin film of cellulose (10 mu thick).
      Duraplasty was performed using a 50-mu-thick cellulose membrane to complete the
      procedure and the animals were observed over a period of 270 days. Group III
      animals (six dogs) underwent smaller (1-cm diameter) bilateral parietal
      craniectomy, which included additional covering of the dura on the left side with
      50-mu-thick cellulose and a suture of temporalis muscle. This group was observed
      for 40, 60, 80, or 120 days. Transient mild clinical symptoms were observed
      during the early postoperative period. At autopsy, macroscopic examination
      demonstrated good acceptance of the grafts with few and moderate extradural
      fibrosis, which caused adherence of the implants to the bone fragment. No
      adherence to the cortex was observed. Microscopic examination demonstrated
      absence of graft adherence to the cortical surface even when the cortex was
      injured. The cellulose was enveloped by two layers of connective tissue, the
      external layer being thicker than the internal one. Cellulose fibers increased in
      thickness over time until 30 days and then decreased in thickness until 270 days.
      This decrease in thickness between 30 to 270 days was statistically significant
      (p < 0.05). The physical properties of biosynthetic cellulose and the low
      cellular reaction to its implantation qualify this material as a dural
      substitute. Additional long-term studies must be undertaken to complete this
      report.

PMID- 8988095
TI  - Regional parenchymal enhancement with mixed cavernous/venous malformations of the
      brain. Case report.
AB  - With improvements in imaging technology, the detection of both cavernous
      malformations and venous malformations has increased markedly in recent years.
      Although much has been learned about the association of cavernous and venous
      malformations, important questions regarding the true nature of such a
      relationship remain unanswered. It has been proposed that certain venous
      malformations produce local venous hypertension with resultant microhemorrhage,
      growth factor release, and creation of cavernous malformations. The authors
      report on two patients with cerebellopontine venous malformations associated with
      cavernous malformations. Both patients demonstrated persistent regional
      parenchymal enhancement associated with the vascular malformations. In addition,
      both patients had significant clinical symptoms referable to the region of
      affected brain. This previously undescribed finding may represent an imaging
      correlate to the complex interaction among venous malformations, venous
      hypertension, and cavernous malformations.

PMID- 8988094
TI  - Primary endodermal sinus tumor presenting with spinal cord compression. Case
      report.
AB  - Endodermal sinus tumor is an uncommon malignant germ-cell neoplasm. These tumors
      usually present in childhood or young adulthood as testicular or ovarian masses;
      however, mediastinal and intracranial tumors have been described. The authors
      report the occurrence of a primary paraspinal endodermal sinus tumor in a 21
      month-old boy who presented with thoracic spinal cord compression. A review of
      the literature failed to reveal a similar case. The clinical presentation,
      radiographic characteristics, operative findings, and patient outcome are
      discussed.

PMID- 8988096
TI  - Hyperactive pectoralis reflex as an indicator of upper cervical spinal cord
      compression. Report of 15 cases.
AB  - Myelopathy from cervical spondylosis is often accompanied by hyperreflexia of the
      upper-extremity deep tendon reflexes (DTRs). Reflexes such as the pectoralis jerk
      and the deltoid jerk may only be apparent in the context of hyperreflexia.
      Although the nerve roots involved in the reflex arcs are well described, levels
      of cervical spinal cord compression that lead to the hyperreflexia are not as
      clear. This is of particular significance for patients with multilevel cervical
      spondylosis in determining the levels responsible for their symptoms. The authors
      examined 15 consecutive patients who presented for treatment of cervical
      myelopathy. The clinical examination was then correlated with levels of cervical
      spinal cord compression by cervical magnetic resonance imaging or computerized
      tomography with intrathecal contrast enhancement. The presence of a prominent
      pectoralis jerk was seen only in patients with spinal cord compression at the C2
      3 and/or C3-4 levels (nine patients). No patient with compression at or below the
      C4-5 disc space without coexisting compression at a higher level had hyperactive
      pectoralis reflexes. This association between the C3-4 level and a hyperactive
      pectoralis reflex was significant (p < 0.004, Fisher's exact test). The deltoid
      reflex was tested in the last nine consecutive patients. It was present in
      patients with compression of the upper spinal cord at levels C3-4 and C4-5 (four
      of five patients) but appeared in only one of four patients with compression
      below C4-5. This association did not attain statistical significance. The
      presence of a hyperactive pectoralis reflex is specific for lesions of the upper
      cervical spinal cord. Examination of upper-extremity DTRs may be helpful in
      planning the appropriate levels for surgical decompression in patients with
      multilevel spondylosis and myelopathy.

PMID- 8988097
TI  - Tumoral calcinosis of the cervical spine in an infant. Case illustration.

PMID- 8988098
TI  - Intracranial hypotension.

PMID- 8988099
TI  - Surgery or radiosurgery?

PMID- 8988100
TI  - Surgery or radiosurgery.

PMID- 8988101
TI  - Surgery or radiosurgery.

PMID- 8988102
TI  - Surgery or radiosurgery.

PMID- 8988103
TI  - Recurrent AVMs after negative angiography.

PMID- 8988104
TI  - Recurrent AVMs after negative angiography.

PMID- 8988105
TI  - Trigeminal neuralgia and contralateral mass.

PMID- 8988107
TI  - And now all this.

PMID- 8988106
TI  - Heat shock protein.

PMID- 8988108
TI  - Immune system in suicide-gene therapy.

PMID- 8988109
TI  - Clinical implications of lamivudine resistance by HBV.

PMID- 8988110
TI  - Few psychological consequences of presymptomatic testing for Huntington disease.

PMID- 8988111
TI  - Opioids in labour--no analgesic effect.

PMID- 8988112
TI  - Bile acid research and applications.

PMID- 8988113
TI  - Pardonable revisions and protocol reviews.

PMID- 8988114
TI  - Ambulatory blood pressure in pregnancy and fetal growth.
AB  - BACKGROUND: Retarded growth in utero has been linked with high blood pressure and
      other risk factors for cardiovascular disease in adult life. However, the
      influence on fetal growth of the maternal blood pressure during pregnancy is not
      well defined. In a prospective study, we examined the relation between maternal
      ambulatory blood pressure during pregnancy and indices of fetal growth. METHODS:
      We studied 209 healthy nulliparous pregnant women referred to an inner-city
      district general hospital (86% of 244 consecutively referred women who met the
      study criteria). 24 h ambulatory blood-pressure recordings were obtained in early
      (median 18 weeks [IQR 17-18]) mid (28 weeks [28]), and late (36 weeks [36])
      gestation. Eight infants delivered before 32 weeks' gestation were excluded from
      the analysis. FINDINGS: A 5 mm Hg (1 SD) increase in mean 24 h diastolic blood
      pressure at 28 weeks' gestation was associated with a 68 g (95% Cl 3-132)
      decrease in birthweight; a similar change in diastolic pressure at 36 weeks'
      gestation was associated with a 76 g (24-129) decrease in birthweight. These
      associations were independent of potential confounders (maternal age, height,
      weight, cigarette smoking, alcohol intake, ethnic origin, pregnancy hypertension
      syndromes, and preterm birth). Maternal mean 24 h diastolic blood pressure at 28
      weeks' gestation was also inversely associated with the infant's ponderal index
      at birth in multivariate analysis (p = 0.06). Higher maternal ambulatory blood
      pressure at 28 weeks' and 36 weeks' gestation also predicted lower head
      circumference, although these associations were dependent on birthweight.
      Associations between ambulatory systolic blood pressure and indices of fetal
      growth were weak and inconsistent and ambulatory blood pressure at 18 weeks'
      gestation did not predict fetal growth. INTERPRETATION: There is a continuous
      inverse association between fetal growth and maternal blood pressure, throughout
      the range seen in normal pregnancy. Maternal blood pressure may be an important
      confounding factor in the reported associations between fetal growth retardation
      and adult hypertension and cardiovascular disease.

PMID- 8988115
TI  - A randomised, prospective, double-blind, placebo-controlled trial of glyceryl
      trinitrate ointment in treatment of anal fissure.
AB  - BACKGROUND: Anal fissure is most commonly treated surgically by internal anal
      sphincterotomy. However, there is some concern over the effects of this procedure
      on continence. Nitric oxide donors such as glyceryl trinitrate (GTN) have been
      shown to cause a reversible chemical sphincterotomy capable of healing fissures
      in a small series of cases. This study reports a prospective, randomised, double
      blind, placebo-controlled trial to test the hypothesis that topical GTN is the
      best first-line treatment for chronic anal fissure. METHODS: 80 consecutive
      patients were randomised to receive treatments with topical 0.2% GTN ointment or
      placebo. Maximum anal resting pressure (MARP) was measured with a constantly
      perfused side-hole catheter before and after the first application of trial
      ointment. Anodermal blood flow was measured during manometry by laser Doppler
      flowmetry. After initial treatments, patients were given a supply of ointment
      (either GTN or placebo) to be applied to the lower anal canal twice daily.
      Patients were reviewed 2-weekly. At the initial and follow up visits patients
      were asked to record pain experienced on defaecation on a linear analogue pain
      score. Endpoints were healing of the fissure or condition after 8 weeks of
      treatment. FINDINGS: After 8 weeks, healing was observed in 26/38 (68%) patients
      treated with GTN and in 3/39 (8%) patients treated with placebo (p < 0.0001, chi
      2 test). Linear analogue pain score fell significantly in both groups after 2
      weeks of treatment. This fall was maintained in those treated with GTN but pain
      scores returned to pre-treatment values by 4 weeks on treatment with placebo.
      MARP fell significantly from a mean of 115.9 (SD 31.6) to 75.9 (30.1) cm H2O (p <
      0.001, Student's paired t-test) in patients treated with GTN but no change was
      seen in MARP after placebo. Anodermal blood flow measured by laser Doppler
      flowmetry significantly increased after application of GTN ointment but was
      unaffected by placebo. INTERPRETATION: Topical GTN provides rapid, sustained
      relief of pain in patients with anal fissure. Over two-thirds of patients treated
      in this way avoided surgery which would otherwise have been required for healing.
      Long-term follow up is needed to assess the risk of recurrent fissure in patients
      with GTN.

PMID- 8988116
TI  - Measles vaccination and Guillain-Barre syndrome.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) has been associated with several
      infectious agents, and the possibility that the disorder may be caused by
      vaccination has been raised. We compared the numbers of cases of GBS observed
      immediately after mass measles vaccination campaigns with the numbers that would
      be expected from baseline rates, to assess whether there is a causal relation
      between measles vaccination and GBS. METHODS: We analysed data on 2296 cases of
      GBS reported to the Poliomyelitis Eradication Surveillance System of the Pan
      American Health Organization as cases of suspected poliomyelitis. These cases
      occurred among 73 million immunised children aged 9 months to 15 years in
      Argentina, Brazil, Chile, and Colombia, between January, 1990, and December,
      1994. These children were targeted for mass measles vaccination campaigns (each
      lasting 1 month) in 1992 and 1993. The frequency of GBS cases observed during the
      vaccination campaigns or the next 42 days (the latent period) was compared with
      that during the rest of the study period, with the assumption of a Poisson
      distribution. FINDINGS: The average annual incidence of GBS was 0.62 per 100000
      children aged 1-14 years. The number of cases that would be expected within any
      72-day period would therefore be 92. The average observed number of cases during
      latent periods after measles vaccination was 97. The probability that 97 or more
      cases would occur during a period with an expected number of 92 was 0.31.
      INTERPRETATION: The average annual rates of GBS by age-group for the 5 years
      analysed were consistent with previous data; thus we are confident that the
      surveillance system is sufficiently sensitive. There was no statistically
      significant association between measles vaccination and GBS. If there is any
      causal relation, the number of GBS cases due to measles vaccination was so small
      that data from the vaccination of more than 70 million children were not
      sufficient to detect a rise in the number of observed GBS cases beyond the
      expected number.

PMID- 8988117
TI  - Are younger children at highest risk of renal sequelae after pyelonephritis?
AB  - BACKGROUND: The general belief about the relation between risk of renal sequelae
      after pyelonephritis and age is that infants are at highest risk and children
      older than 5 years at lower risk. This assumption has led to differences in
      treatment based on age. The aim of this prospective study was to investigate the
      occurrence of renal lesions in children aged 0-16 years. METHODS: Between May,
      1994, and January, 1996, all children aged 0-16 years who were admitted to our
      department with a diagnosis of probable pyelonephritis and a positive urine
      culture were included in this prospective study. All patients received
      antibiotics for 7-21 days. During the acute phase of urinary-tract infection,
      scintigraphy with technetium-99m-dimercaptosuccinic acid (DMSA) and
      ultrasonography were done. Voiding cystourethrography was undertaken at least 6
      weeks after the end of antibiotic treatment. When scintigraphy showed renal
      parenchymal lesions, repeat scintigraphy was done after at least 2 months to
      assess the progression of renal lesions. For the analysis, children were grouped
      by age according to presumed risk of renal sequelae after pyelonephritis: high
      risk (< 1 year), moderate risk (1-5 years), low risk (> 5 years). FINDINGS: 201
      patients were enrolled in the study (119 < 1 year, 47 aged 1-5 years, 35 > 5
      years). During the acute phase of urinary-tract infection, renal lesions were
      found in 66 (55%) infants under 1 year, in 37 (79%) children aged 1-5 years, and
      in 24 (69%) children older than 5 years. Of these 127 children, 108 underwent
      repeat scintigraphy after an average of 3 months (50 < 1 year, 36 aged 1-5 years,
      22 > 5 years). Overall, renal scars were found on repeat scintigraphy in 20 (40%)
      infants under 1 year, in 31 (86%) children aged 1-5 years, and in 14 (64%)
      children older than 5 years. 38 (36%) of these 65 patients had vesicoureteric
      reflux. Among 88 children who had a first documented urinary-tract infection and
      underwent repeat scintigraphy, renal scars were found in 20 (43%) under 1 year,
      in 26 (84%) aged 1-5 years, and in eight (80%) older than 5 years.
      INTERPRETATION: This study did not confirm the conventional view that the risk of
      renal scars after pyelonephritis diminishes with age. We believe that all
      children, irrespective of age, will benefit from any measure that prevents the
      development of renal sequelae.

PMID- 8988118
TI  - Hepatitis-B-virus resistance to lamivudine given for recurrent infection after
      orthotopic liver transplantation.
AB  - BACKGROUND: Orthotopic liver transplantation for end-stage hepatitis-B-virus
      (HBV) infection is commonly complicated by recurrence of HBV. Lamivudine, a
      cytosine nucleoside analogue, has been shown to suppress HBV infection. We report
      the development of resistance to lamivudine in three patients who underwent
      transplantation for end-stage liver disease secondary to hepatitis B. METHODS:
      Two of the patients received lamivudine for recurrent HBV infection after
      transplantation, whereas the third patient began treatment 1 month before
      transplantation in an attempt to prevent HBV recurrence after transplantation.
      The three patients initially responded well to treatment, but viral recurrence
      occurred after 9-10 months of treatment in all patients. HBV DNA was amplified
      from serum and sequenced through a conserved polymerase domain-the tyrosine,
      methionine, aspartate, aspartate (YMDD) locus. We assessed the susceptibility of
      HBV to lamivudine by infecting primary human hepatocytes with serum taken before
      the start of treatment and after recurrence in varying concentrations of
      lamivudine. FINDINGS: DNA sequencing showed a common mutation within the YMDD
      locus of the HBV polymerase gene in all patients during lamivudine treatment. In
      hepatocyte cultures infected with pretreatment serum, HBV DNA concentrations were
      reduced to less than 6% of those in control cultures by addition of lamivudine in
      concentrations as low as 0.03 mumol/L. By contrast, in cultures treated with
      serum taken after recurrence, HBV DNA concentrations did not fall below 20% of
      control values, even with lamivudine at 30 mumol/L. INTERPRETATION: Resistance to
      lamivudine has been reported in HIV patients with mutations in the YMDD locus of
      the polymerase gene. Our findings indicate a common mechanism of lamivudine
      resistance for HIV and HBV that involves similar point mutations in homologous
      domains of the viral polymerases.

PMID- 8988119
TI  - Plasmodium falciparum malaria transmitted in hospital through heparin locks.
AB  - BACKGROUND: After a community investigation had implicated hospital admission as
      a shared feature of a cluster of acute Plasmodium falciparum malaria (AFM) cases
      in Riyadh, Saudi Arabia, we began an in-hospital investigation to determine the
      method of transmission. METHODS: We investigated all AFM patients admitted to one
      paediatric hospital for any reason from December, 1991, to April, 1992. We
      classified AFM as locally acquired (LAFM) if during the month before AFM onset
      the patient had not visited a malarious area, and as hospital acquired (HAFM) if
      the LAFM patient had been admitted to hospital during that month. We compared
      exposures of HAFM cases with those of other patients sampled from the same wards.
      We observed nursing practices and investigated by anonymous questionnaire how
      nurses administered parenteral drugs. FINDINGS: Of 21 LAFM cases, 20 (95%) had a
      previous hospital admission (exposure admission) compared with 15 (25%) of 61
      other patients (p < 0.001; chi 2 test). During the exposure admission, all HAFM
      patients had occupied the same room as, or a room adjacent to, an AFM patient; 14
      (23%) of 60 other patients occupied the same room or rooms adjacent to an AFM
      patient (p < 0.001, chi 2). 90% of HAFM patients received infusions through a
      heparin lock during the exposure admission, compared with 49% of 120 general
      patients (p < 0.001, chi 2). 10% of nurses admitted to using one syringe for more
      than one heparin lock and 50% filled syringes with enough heparin for three to
      ten heparin locks. INTERPRETATION: P falciparum was transmitted between patients
      when single syringes were used on heparin locks of sequential patients. This
      practice would easily transmit other blood-borne agents.

PMID- 8988120
TI  - Falling again.

PMID- 8988121
TI  - Guillain-Barre syndrome in mother and newborn child.

PMID- 8988122
TI  - Dyspareunia and vulvodynia: unrecognised manifestations of symptomatic
      dermographism.

PMID- 8988124
TI  - Occlusive paromomycin for cutaneous leishmaniasis.

PMID- 8988123
TI  - Old-world leishmaniasis of the auricle.

PMID- 8988125
TI  - Pregnancy after treatment with three recombinant gonadotropins.

PMID- 8988126
TI  - New variant Creutzfeldt-Jakob disease in France.

PMID- 8988127
TI  - Finger clubbing and HIV infection in Malawian children.

PMID- 8988129
TI  - President Clinton wages public war against AIDS.

PMID- 8988128
TI  - Regression of immunoproliferative small intestinal disease after eradication of
      Helicobacter pylori.

PMID- 8988130
TI  - Cardiac pacing.

PMID- 8988131
TI  - Insulin analogues.

PMID- 8988132
TI  - Culture, media, and HIV/AIDS in Asia.

PMID- 8988133
TI  - Perinatal necropsy by magnetic resonance imaging.

PMID- 8988134
TI  - Perinatal necropsy by magnetic resonance imaging.

PMID- 8988135
TI  - Perinatal necropsy by magnetic resonance imaging.

PMID- 8988136
TI  - Co-sleeping and sudden infant death syndrome.

PMID- 8988137
TI  - Chronic fatigue syndrome.

PMID- 8988138
TI  - Toxicity of tungsten.

PMID- 8988139
TI  - Routine prenatal screening for congenital heart disease.

PMID- 8988140
TI  - Incidental eradication of Helicobacter pylori.

PMID- 8988141
TI  - Demographic and nutritional consequences of civil war in Liberia.

PMID- 8988142
TI  - Unscrupulous trade in needles for reuse.

PMID- 8988143
TI  - M tuberculosis drug resistance in AIDS.

PMID- 8988144
TI  - M tuberculosis drug resistance in AIDS.

PMID- 8988145
TI  - Absence of awareness of primary HIV infection.

PMID- 8988146
TI  - Change in male:female ratio among newborn babies in Netherlands.

PMID- 8988147
TI  - Peer review and grant applications.

PMID- 8988148
TI  - Peer review and grant applications.

PMID- 8988149
TI  - Peer review and grant applications.

PMID- 8988150
TI  - Health sector reform and rise of caesarean birth in Chile.

PMID- 8988151
TI  - Increased mortality in US nuclear test veterans.

PMID- 8988153
TI  - Zafirlukast for asthma.

PMID- 8988154
TI  - Mirtazapine--a new antidepressant.

PMID- 8988155
TI  - Brave new now.

PMID- 8988156
TI  - Twist and shout.

PMID- 8988157
TI  - Linking chromosomal clues.

PMID- 8988158
TI  - Landmarks in the Rosetta Stone of mammalian comparative maps.

PMID- 8988159
TI  - Leaving Kansas ... finding genes in 1997.

PMID- 8988160
TI  - P1148A in fibrillin-1 is not a mutation anymore.

PMID- 8988161
TI  - PMP22 Thr(118)Met: recessive CMT1 mutation or polymorphism?

PMID- 8988162
TI  - A breast/ovarian cancer patient with germline mutations in both BRCA1 and BRCA2.

PMID- 8988163
TI  - Ethical issues in genetic research: disclosure and informed consent.
AB  - As research to correlate genetic status with predisposition to disease has
      accelerated, so has the concern that participation in such studies creates the
      risk of genetic discrimination and emotional distress. There is a need to broaden
      disclosure during the consent process to ensure that potential subjects
      understand these risks and other issues and to address them in the consent form.
      We describe the broad approach that we have taken in regard to disclosure and
      consent in gene mapping studies.

PMID- 8988164
TI  - Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T)
      gene family.
AB  - Holt-Oram syndrome is a developmental disorder affecting the heart and upper
      limb, the gene for which was mapped to chromosome 12 two years ago. We have now
      identified a gene for this disorder (HOS1). The gene (TBX5) is a member of the
      Brachyury (T) family corresponding to the mouse Tbx5 gene. We have identified six
      mutations, three in HOS families and three in sporadic HOS cases. Each of the
      mutations introduces a premature stop codon in the TBX5 gene product. Tissue in
      situ hybridization studies on human embryos from days 26 to 52 of gestation
      reveal expression of TBX5 in heart and limb, consistent with a role in human
      embryonic development.

PMID- 8988165
TI  - Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt
      Oram syndrome.
AB  - Holt-Oram syndrome is characterized by upper limb malformations and cardiac
      septation defects. Here, we demonstrate that mutations in the human TBX5 gene
      underlie this disorder. TBX5 was cloned from the disease locus on human
      chromosome 12q24.1 and identified as a member of the T-box transcription factor
      family. A nonsense mutation in TBX5 causes Holt-Oram syndrome in affected members
      of one family; a TBX5 missense mutation was identified in affected members of
      another. We conclude that TBX5 is critical for limb and heart development and
      suggest that haploinsufficiency of TBX5 causes Holt-Oram syndrome.

PMID- 8988166
TI  - Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre
      Chotzen syndrome.
AB  - Saethre-Chotzen syndrome is one of the most common autosomal dominant disorders
      of craniosynostosis in humans and is characterized by craniofacial and limb
      anomalies. The locus for Saethre-Chotzen syndrome maps to chromosome 7p21-p22. We
      have evaluated TWIST, a basic helix-loop-helix transcription factor, as a
      candidate gene for this condition because its expression pattern and mutant
      phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen
      phenotype. We mapped TWIST to human chromosome 7p21-p22 and mutational analysis
      reveals nonsense, missense, insertion and deletion mutations in patients. These
      mutations occur within the basic DNA binding, helix I and loop domains, or result
      in premature termination of the protein. Studies in Drosophila indicate that
      twist may affect the transcription of fibroblast growth factor receptors (FGFRs),
      another gene family implicated in human craniosynostosis. The emerging cascade of
      molecular components involved in craniofacial and limb development now includes
      TWIST, which may function as an upstream regulator of FGFRs.

PMID- 8988167
TI  - Mutations of the TWIST gene in the Saethre-Chotzen syndrome.
AB  - Saethre-Chotzen syndrome (acrocephalo-syndactyly type III, ACS III) is an
      autosomal dominant craniosynostosis with brachydactyly, soft tissue syndactyly
      and facial dysmorphism including ptosis, facial asymmetry and prominent ear
      crura. ACS III has been mapped to chromosome 7p21-22. Of interest, TWIST, the
      human counterpart of the murine Twist gene, has been localized on chromosome 7p21
      as well. The Twist gene product is a transcription factor containing a basic
      helix-loop-helix (b-HLH) domain, required in head mesenchyme for cranial neural
      tube morphogenesis in mice. The co-localisation of ACS III and TWIST prompted us
      to screen ACS III patients for TWIST gene mutations especially as mice
      heterozygous for Twist null mutations displayed skull defects and duplication of
      hind leg digits. Here, we report 21-bp insertions and nonsense mutations of the
      TWIST gene (S127X, E130X) in seven ACS III probands and describe impairment of
      head mesenchyme induction by TWIST as a novel pathophysiological mechanism in
      human craniosynostoses.

PMID- 8988168
TI  - Comparative anchor tagged sequences (CATS) for integrative mapping of mammalian
      genomes.
AB  - Precise comparisons of mammalian gene maps require common anchor loci as
      landmarks for conserved chromosomal segments. Using a computer script that
      automates DNA sequence database alignments, we designed 410 evolutionarily
      conserved primer pair sequences which are specific for anchor locus gene
      amplification from any mammalian species' DNA. Primer pairs were designed to span
      introns for polymorphism ascertainment, and to include sufficient exonic sequence
      (25-400 bp) to allow for gene identification. A total of 318 primer pairs were
      optimized for domestic cats, and 86% of the sequenced feline PCR products showed
      homology to the gene of primer origin. A screen of 20 mammals from 11 orders
      revealed that 35-52% of the 318 primers yielded a single PCR product without
      further optimization suggesting that nearly 75% can be optimized for any
      eutherian mammal.

PMID- 8988169
TI  - The mitochondrial genome of Arabidopsis thaliana contains 57 genes in 366,924
      nucleotides.
AB  - We have determined the complete sequence of the mitochondrial DNA in the model
      plant species Arabidopsis thaliana, affording access to the first of its three
      genomes. The 366,924 nucleotides code for 57 identified genes, which cover only
      10% of the genome. Introns in these genes add about 8%, open reading frames
      larger than 100 amino acids represent 10% of the genome, duplications account for
      7%, remnants of retrotransposons of nuclear origin contribute 4% and integrated
      plastid sequences amount to 1%-leaving 60% of the genome unaccounted for. With
      the significant contribution of duplications, imported foreign DNA and the
      extensive background of apparently functionless sequences, the mosaic structure
      of the Arabidopsis thaliana mitochondrial genome features many aspects of size
      relaxed nuclear genomes.

PMID- 8988170
TI  - Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine
      expansions in the alpha 1A-voltage-dependent calcium channel.
AB  - A polymorphic CAG repeat was identified in the human alpha 1A voltage-dependent
      calcium channel subunit. To test the hypothesis that expansion of this CAG repeat
      could be the cause of an inherited progressive ataxia, we genotyped a large
      number of unrelated controls and ataxia patients. Eight unrelated patients with
      late onset ataxia had alleles with larger repeat numbers (21-27) compared to the
      number of repeats (4-16) in 475 non-ataxia individuals. Analysis of the repeat
      length in families of the affected individuals revealed that the expansion
      segregated with the phenotype in every patient. We identified six isoforms of the
      human alpha 1A calcium channel subunit. The CAG repeat is within the open reading
      frame and is predicted to encode glutamine in three of the isoforms. We conclude
      that a small polyglutamine expansion in the human alpha 1A calcium channel is
      most likely the cause of a newly classified autosomal dominant spinocerebellar
      ataxia, SCA6.

PMID- 8988171
TI  - UBE3A/E6-AP mutations cause Angelman syndrome.
AB  - Angelman syndrome (AS), characterized by mental retardation, seizures, frequent
      smiling and laughter, and abnormal gait, is one of the best examples of human
      disease in which genetic imprinting plays a role. In about 70% of cases, AS is
      caused by de novo maternal deletions at 15q11-q13 (ref. 2). Approximately 2% of
      AS cases are caused by paternal uniparental disomy (UPD) of chromosome 15 (ref.
      3) and 2-3% are caused by "imprinting mutations'. In the remaining 25% of AS
      cases, no deletion, uniparental disomy (UPD), or methylation abnormality is
      detectable, and these cases, unlike deletions or UPD, can be familial. These
      cases are likely to result from mutations in a gene that is expressed either
      exclusively or preferentially from the maternal chromosome 15. We have found that
      a 15q inversion inherited by an AS child from her normal mother disrupts the 5'
      end of the UBE3A (E6-AP) gene, the product of which functions in protein
      ubiquitination. We have looked for novel UBE3A mutations in nondeletion/non
      UPD/non-imprinting mutation (NDUI) AS patients and have found one patient who is
      heterozygous for a 5-bp de novo tandem duplication. We have also found in two
      brothers a heterozygous mutation, an A to G transition that creates a new 3'
      splice junction 7 bp upstream from the normal splice junction. Both mutations are
      predicted to cause a frameshift and premature termination of translation. Our
      results demonstrate that UBE3A mutations are one cause of AS and indicate a
      possible abnormality in ubiquitin-mediated protein degradation during brain
      development in this disease.

PMID- 8988172
TI  - De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in
      Angelman syndrome.
AB  - Angelman syndrome (AS) is associated with maternal deletions of human chromosome
      15q11-q13 and with paternal uniparental disomy for this region indicating that
      deficiency of an imprinted, maternally expressed gene within the critical
      interval is the likely cause of the syndrome. Although the gene for E6-AP
      ubiquitin-protein ligase (UBE3A) was mapped to the critical region for AS,
      evidence of expression from both parental alleles initially suggested that it was
      an unlikely candidate gene for this disorder. Because attempts to identify any
      novel maternally expressed transcripts were unsuccessful and because the UBE3A
      gene remained within a narrowed AS critical region, we searched for mutations in
      UBE3A in 11 AS patients without known molecular defects (large deletion,
      uniparental disomy, or imprinting mutation). This analysis tested the possibility
      that deficiency of an undefined, maternally expressed transcript or isoform of
      the UBE3A gene could cause AS. Four mutations were identified including a de novo
      frameshift mutation and a de novo nonsense mutation in exon 3 and two missense
      mutations of less certain significance. The de novo truncating mutations indicate
      that UBE3A is the AS gene and suggest the possibility of a maternally expressed
      gene product in addition to the biallelically expressed transcript. Intragenic
      mutation of UBE3A in AS is the first example of a genetic disorder of the
      ubiquitin-dependent proteolytic pathway in mammals. It may represent an example
      of a human genetic disorder associated with a locus producing functionally
      distinct imprinted and biallelically expressed gene products.

PMID- 8988173
TI  - AP2 inhibits cancer cell growth and activates p21WAF1/CIP1 expression.
AB  - The 52-kD Activator Protein (AP2) is a DNA-binding transcription factor
      implicated in signalling terminal differentiation. Profound developmental
      abnormalities have been recently observed in AP2-null mice. The molecular events
      by which AP2 promotes differentiation or development are, however, unknown.
      Increased expression of the universal cell cycle inhibitor p21WAF1/CIP1 occurs in
      growth-arrested terminally differentiating cells. In a search for cellular
      factors that could activate p21 during phorbol ester (TPA)-induced
      differentiation, we identified AP2 as a regulator of p21 expression. Mutagenesis
      of an AP2 DNA-binding site within a p21 promoter-luciferase reporter inhibited
      its activation by either AP2 transfection or TPA stimulation. Endogenous p21
      protein levels were elevated and DNA synthesis was inhibited in AP2 versus
      control vector-transfected cells. Overexpression of AP2 in HepG2 human
      hepatoblastoma and SW480 human colon adenocarcinoma cells inhibited cell division
      and stable colony formation. These results link the differentiation-associated
      factor AP2 to negative cell cycle and growth control, possibly through p21
      activation.

PMID- 8988174
TI  - Delayed early embryonic lethality following disruption of the murine cyclin A2
      gene.
AB  - In higher eukaryotes, cell cycle progression is controlled by cyclin dependent
      kinases (Cdks) complexed with cyclins. A-type cyclins are involved at both G1/S
      and G2/M transitions of the cell cycle. Cyclin A2 activates cdc2 (Cdk1) on
      passage into mitosis and Cdk2 at the G1/S transition. Antisense constructs, or
      antibodies directed against cyclin A2 block cultured mammalian cells at both of
      these transitions. In contrast, overexpression of cyclin A2 appears to advance S
      phase entry and confer anchorage-independent growth, and can lead to apoptosis. A
      second A-type cyclin, cyclin A1 has been described recently which, in the mouse,
      is expressed in germ cells but not somatic tissues. To address the possible
      redundancy between different cyclins in vivo and also the control of early
      embryonic cell cycles, we undertook the targeted deletion of the murine cyclin A2
      gene. The homozygous null mutant is embryonically lethal, demonstrating that the
      cyclin A2 gene is essential. Surprisingly, homozygous null mutant embryos develop
      normally until post-implantation, around day 5.5 p.c. This observation may be
      explained by the persistence of a maternal pool of cyclin A2 protein until at
      least the blastocyst stage, or an unexpected role for cyclin A1 during early
      embryo development.

PMID- 8988175
TI  - Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using
      comparative genomic hybridization and targeted linkage analysis.
AB  - Many human cancer susceptibility genes have been successfully mapped by genetic
      linkage studies. One that has so far eluded researchers is that for Peutz-Jeghers
      (P-J) syndrome, a condition characterized by intestinal hamartomatous polyposis
      and melanin spots of the lips, buccal mucosa and digits. A dramatically elevated
      risk of malignancy has also been documented. Gastrointestinal tumours as well as
      cancers of the breast, ovary, testis and uterine cervix appear to be
      overrepresented in families with this syndrome. The nature of hamartomatous
      polyps is equivicol. Hamartomas are usually considered histologically benign, but
      in the case of Peutz-Jeghers patients, there are reports of adenomatous and
      malignant changes in the polyps, and the possibility of a hamartoma-carcinoma
      sequence has been discussed. A search for a putative tumour suppressor locus was
      made using comparative genomic hybridization (CGH) of Peutz-Jeghers polyps,
      combined with loss of heterozygosity (LOH) study. Genetic linkage analysis in 12
      families using markers from a deletion site demonstrated the presence of a high
      penetrance locus in distal 19p with a multipoint lod score of 7.00 at marker
      D19S886 without evidence of genetic heterogeneity. The study demonstrates the
      power of CGH combined with LOH analysis in identifying putative tumour suppressor
      loci, and provides molecular evidence of malignant potential in hamartomas.

PMID- 8988176
TI  - Mutations in SOD1 associated with amyotrophic lateral sclerosis cause novel
      protein interactions.
AB  - A subset of familial and sporadic amyotrophic lateral sclerosis (ALS-a fatal
      disorder characterised by progressive motor neuron degeneration) cases are due to
      mutations in the gene encoding Cu,Zn superoxide dismutase (SOD1). Two mutations
      which have been successfully used to generate transgenic mice that develop an ALS
      like syndrome are glycine 85 to arginine (G85R) and glycine 93 to alanine (G93A)
      with the mutant SOD1 allele overexpressed in a normal mouse genetic background.
      No ALS-like phenotype is observed in mice overexpressing wild-type SOD1 or mice
      without any SOD1 activity. These dominant mutations, which do not necessarily
      decrease SOD1 activity, may confer a gain of function that is selectively lethal
      to motor neurons. The yeast interaction trap system allowed us to determine
      whether these mutations in SOD1 caused novel protein interactions not observed
      with wild-type SOD1 and which might participate in the generation of the ALS
      phenotype. Two proteins, lysyl-tRNA synthetase and translocon-associated protein
      delta, interact with mutant forms of SOD1 but not with wild-type SOD1. The
      specificity of the interactions was confirmed by the coimmunoprecipitation of
      mutant SOD1 and the expressed proteins. These proteins are expressed in ventral
      cord, lending support to the relevance of this interaction to motor neuron
      disease.

PMID- 8988177
TI  - Deregulation of the platelet-derived growth factor B-chain gene via fusion with
      collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell
      fibroblastoma.
AB  - Dermatofibrosarcoma protuberans (DP), an infiltrative skin tumour of intermediate
      malignancy, presents specific features such as reciprocal translocations
      t(17;22)(q22;q13) and supernumerary ring chromosomes derived from the t(17;22).
      In this report, the breakpoints from translocations and rings in DP and its
      juvenile form, giant cell fibroblastoma (GCF), were characterised on the genomic
      and RNA level. These rearrangements fuse the platelet-derived growth factor B
      chain (PDGFB, c-sis proto-oncogene) and the collagen type I alpha 1 (COL1A1)
      genes. PDGFB has transforming activity and is a potent mitogen for a number of
      cell types, but its role in oncogenic processes is not fully understood. COL1A1
      is a major constituent of the connective tissue matrix. Neither PDGFB nor COL1A1
      have so far been implicated in any tumour translocations. These gene fusions
      delete exon 1 of PDGFB, and release this growth factor from its normal
      regulation.

PMID- 8988178
TI  - Low mutation rates of microsatellite loci in Drosophila melanogaster.
AB  - Analysis of variation at microsatellite DNA loci is widely used in studies of
      parentage, linkage and evolutionary history. The utility of microsatellites is
      primarily due to high levels of allelic diversity, believed to reflect mutation
      rates orders of magnitude higher than base pair substitutions at single-copy
      genes. For humans, mice, rats and pigs, microsatellite mutation rates have been
      estimated at 10(-3)-10(-5). However, a recent study comparing microsatellite
      variation in humans with non-human primates suggests that microsatellite mutation
      rates may vary considerably across taxa. We measured mutation rates of 24
      microsatellite loci in mutation accumulation lines of Drosophila melanogaster.
      Surprisingly, only a single mutation was detected after screening 157,680 allele
      generations, yielding an estimated average mutation rate per locus of 6.3 x 10(
      6), a mutation rate considerably lower than reported for various mammals. We
      propose that the comparatively low mutation rate is primarily a function of short
      microsatellite repeat lengths in the D. melanogaster genome.

PMID- 8988179
TI  - Variation of risks of breast and ovarian cancer associated with different
      germline mutations of the BRCA2 gene.
AB  - The breast cancer susceptibility gene BRCA2 on chromosome 13q12-13 has recently
      been identified. Germline mutations of BRCA2 are predicted to account for
      approximately 35% of families with multiple case, early onset female breast
      cancer, and they are also associated with an increased risk of male breast
      cancer, ovarian cancer, prostate cancer and pancreatic cancer. Germline mutations
      of a second cancer susceptibility gene BRCA1 (ref. 5), are associated with a
      strong predisposition to ovarian cancer as well as female breast cancer. Recent
      studies have suggested that the phenotype in BRCA1 families with respect to the
      ratio of breast to ovarian cancer varies with the location of the BRCA1 mutation.
      To determine whether germline mutations in BRCA2 are associated with a similar
      variation in phenotypic risk, we have analysed the distribution of mutations in
      25 families with multiple cases of breast and/or ovarian cancer ascertained in
      the United Kingdom and Eire. These mutations all lead to premature truncation of
      BRCA2 as a result of frameshift deletions/insertions or nonsense mutations.
      Analysis of the mutation distribution along the length of the gene indicates a
      significant genotype-phenotype correlation. Truncating mutations in families with
      the highest risk of ovarian cancer relative to breast cancer are clustered in a
      region of approximately 3.3 kb in exon 11 (P = 0.0004). Published data on
      mutations in 45 other BRCA2-linked families provide support for this correlation.

PMID- 8988180
TI  - Pancreatic agenesis attributable to a single nucleotide deletion in the human
      IPF1 gene coding sequence.
AB  - The homeodomain protein IPF1 (also known as IDX1, STF1 and PDX1; see Methods) is
      critical for development of the pancreas in mice and is a key factor for the
      regulation of the insulin gene in the beta-cells of the endocrine pancreas.
      Targeted disruption of the Ipf1 gene encoding IPF1 in transgenic mice results in
      a failure of the pancreas to develop (pancreatic agenesis). Here, we report the
      identification of a single nucleotide deletion within codon 63 of the human IPF1
      gene (13q12.1) in a patient with pancreatic agenesis. The patient is homozygous
      for the point deletion, whereas both parents are heterozygotes for the same
      mutation. The deletion was not found in 184 chromosomes from normal individuals,
      indicating that the mutation is unlikely to be a rare polymorphism. The point
      deletion causes a frame shift at the C-terminal border of the transactivation
      domain of IPF1 resulting in the translation of 59 novel codons before
      termination, aminoproximal to the homeodomain essential for DNA binding.
      Expression of mutant IPF1 in Cos-1 cells confirms the expression of a prematurely
      terminated truncated protein of 16 kD. Thus, the affected patient should have no
      functional IPF1 protein. Given the essential role of IPF1 in pancreas
      development, it is likely that this autosomal recessive mutation is the cause of
      the pancreatic agenesis phenotype in this patient. Thus, IPF1 appears to be a
      critical regulator of pancreas development in humans as well as mice.

PMID- 8988181
TI  - Affirmative action.

PMID- 8988182
TI  - Imaging of hepatic cirrhosis.

PMID- 8988183
TI  - MR imaging of the brain in epidemiologic research: the Cardiovascular Health
      Study.

PMID- 8988184
TI  - Focused appendix CT technique: a commentary.

PMID- 8988185
TI  - The small renal mass: what is the role of multiphasic helical scanning?

PMID- 8988186
TI  - Assessing contrast on MR images.
AB  - Magnetic resonance imaging pulse sequences are frequently judged by their ability
      to facilitate discrimination between pathologic and normal tissue. Objective
      analysis is usually based on signal intensity measurements. However, the
      literature shows disagreement as to how this analysis should be performed. The
      ability to visually differentiate two objects on the basis of signal intensity
      depends on the contrast-to-noise ratio (CNR). This parameter, however, can be
      calculated only by measuring the intensity of photons reaching the eye from two
      distinct objects and, hence, is display dependent. The signal difference-to-noise
      ratio (SDNR) is a display-independent parameter that reflects the contrast
      generating ability of a pulse sequence. When comparing two imaging sequences, the
      SDNR is proportional to the CNR, assuming the images being compared are displayed
      so that corresponding regions have the same intensity (i.e., photon fluxes).
      Because the SDNR is display independent, it should be the preferred parameter for
      assessing the contrast-generating ability of a pulse sequence. The value and
      limitations of these parameters are discussed.

PMID- 8988187
TI  - Is comparison of mechanical versus pulse-spray thrombolysis in dogs highly
      relevant clinically?

PMID- 8988188
TI  - Like cats and dogs: no perfect animal model for thrombolysis.

PMID- 8988189
TI  - Sulcal, ventricular, and white matter changes at MR imaging in the aging brain:
      data from the cardiovascular health study.
AB  - PURPOSE: To determine the distribution of changes in sulcal size, ventricular
      size, and white matter signal intensity depicted on cranial magnetic resonance
      (MR) images, with stratification according to age, race, and sex. MATERIALS AND
      METHODS: Ventricular size, sulcal size, and white matter signal intensity changes
      were graded on cranial MR images of 3,660 community-living, elderly participants
      in the Cardiovascular Health Study. A healthier subgroup was also defined.
      Summary statistics for both groups were generated for age, race, and sex.
      RESULTS: Regression models of the entire imaged cohort showed higher grades of
      all variables with increasing age, and higher ventricular and sulcal grades in
      men and in nonblack individuals. White matter grade was greater in women and in
      black individuals. Regression models of the healthier subgroup showed similar
      associations, except for a lack of association of sulcal and ventricular size
      with race. CONCLUSION: Sulcal width, ventricular size, and white matter signal
      intensity change with age, sex, and race. Knowledge of these changes is important
      in appropriate interpretation of MR images of the elderly.

PMID- 8988190
TI  - Clinically serious abnormalities found incidentally at MR imaging of the brain:
      data from the Cardiovascular Health Study.
AB  - PURPOSE: To determine the prevalence of clinically serious findings unrelated to
      stroke on cranial magnetic resonance (MR) images in a population of community
      dwelling elderly people. MATERIALS AND METHODS: Neuroradiologists reviewed MR
      images of 3,672 people aged 65 years and older who were enrolled in a
      longitudinal, population-based study of cardiovascular and cerebrovascular
      disease. The neuroradiologists alerted MR imaging field centers about potentially
      serious abnormalities. Clinical information was obtained from clinical
      examinations performed before MR imaging, hospital discharge summaries, and the
      field centers at which MR imaging was performed. RESULTS: On 3,672 image sets, 64
      (1.74%) clinically serious abnormalities were found. Among the presumptive
      diagnoses were 19 meningiomas (0.52%), six pituitary adenomas (0.16%), five
      cavernous malformations (0.14%), eight vascular stenoses (0.22%), four aneurysms
      (0.11%), two intraventricular masses (0.05%), two subdural fluid collections
      (0.05%), and two other tumors (0.05%). Only nine participants with these
      abnormalities required surgery. All but one of the meningiomas were in women, and
      the prevalence of the tumor decreased with increasing age. CONCLUSION: Physicians
      should be alert to the possible presence of clinically serious conditions in
      otherwise asymptomatic elderly individuals.

PMID- 8988191
TI  - Infarctlike lesions in the brain: prevalence and anatomic characteristics at MR
      imaging of the elderly--data from the Cardiovascular Health Study.
AB  - PURPOSE: To determine the prevalence and anatomic characteristics of infarctlike
      lesions seen on cranial magnetic resonance (MR) images. MATERIALS AND METHODS:
      The study cohort consisted of 5,888 community-living individuals aged 65 years
      and older enrolled in a longitudinal, population-based study of cardiovascular
      disease. MR images were obtained from 3,658 participants and evaluated by trained
      readers. Lesion size, anatomic location, and signal intensity were recorded.
      Infarctlike lesion was defined as a nonmass, hyperintense region on spin-density-
      and T2-weighted images and, in cerebral white matter and brain stem, a
      hypointense region on T1-weighted images. RESULTS: Infarctlike lesions were
      depicted on MR images of 1,323 (36%) participants. Eighty-five percent (1,128
      participants) had lesions 3 mm or larger in maximum dimension, although 70.9%
      (1,320 of 1,861) of these lesions were 10 mm or less. Lesion prevalence increased
      with age, especially with lesions 3 mm or larger, which increased from 22.1% (86
      of 389) in the 65-69-year age group to 42.9% (88 of 205) in the over-85-year age
      group (P < .0001). Lesion prevalence was slightly greater in men (497 of 1,527
      [32.5%]) than in women (631 of 2,131 [29.6%]), but did not differ between blacks
      and non-blacks. The deep nuclei were the most commonly affected anatomic sites,
      with 78.2% (1,451 of 1,856) of lesions. Lesions that involved the cerebrum and
      posterior fossa accounted for 11.7% (218 of 1,856) and 10.1% (187 of 1,856) of
      lesions, respectively. CONCLUSION: If the lesions reported in this study indicate
      cerebrovascular disease, subclinical disease may be more prevalent than clinical
      disease, and the prevalence of disease may rise with age. Also, infarctlike
      lesions have a distinctive anatomic profile.

PMID- 8988192
TI  - Orbital pseudotumors: value of short inversion time inversion-recovery MR
      imaging.
AB  - PURPOSE: To evaluate magnetic resonance (MR) signal intensities of orbital
      pseudotumors on short inversion time inversion-recovery (STIR) images and to
      predict the effect of treatment. MATERIALS AND METHODS: Sequential MR
      examinations were performed in 17 patients with orbital pseudotumors, before and
      after treatment. All patients underwent MR imaging with T1- and T2-weighted spin
      echo or fast spin-echo sequences, and STIR sequences with two 0.5-T systems.
      Quantitatively and qualitatively, the differences in signal intensities among
      three therapeutic response groups (good, mild, and no responses) were analyzed
      for each pulse sequence. RESULTS: Quantitatively, both contrast and contrast-to
      noise ratio on STIR images corresponded well to the results of response to
      therapy for all background markers; contrast and contrast-to-noise ratio values
      in the good response group were the largest, while those in the no response group
      were the smallest (P < .0001). Qualitatively, the signal intensities of the
      lesions in the good response group were interpreted as hyperintense to the
      cerebral cortex in 14 (93%) or 11 (73%) of 15 lesions by two observers,
      respectively, while in the no response group, both observers assessed 16 (89%) of
      18 lesions as hypo- or isointense to the muscle (P < .0001). CONCLUSION: STIR
      images showed a variety of signal intensities in the lesions, and the signal
      intensities on the STIR images helped predict the response to the therapy in
      orbital pseudotumors.

PMID- 8988193
TI  - Uveal melanoma: detection of extraocular growth with MR imaging and US.
AB  - PURPOSE: To compare the sensitivity and specificity of magnetic resonance (MR)
      imaging with that of ultrasound (US) in the detection of extraocular extension of
      uveal melanoma. MATERIALS AND METHODS: In 70 patients, the diagnosis of melanoma
      and absence or presence of extraocular growth were confirmed with histologic
      examination (13 patients) or with ophthalmoscopy and surgery (57 patients).
      Unenhanced and enhanced T1-weighted and T2-weighted MR imaging was performed with
      surface coils at 1.5 T. A- and B-mode US scans were obtained with 8- and 10-MHz
      probes, respectively. RESULTS: Extraocular growth was confirmed in seven
      patients: Five patients had retrobulbar tumor, and two had optic nerve
      infiltration. US enabled detection in three cases, whereas six cases were
      diagnosed with MR imaging including both cases of optic nerve infiltration. False
      positive findings were more frequent with US (n = 5) than with MR imaging (n =
      1). CONCLUSION: MR imaging proved to be more sensitive and more specific than US
      in the detection of extraocular extension of uveal melanoma.

PMID- 8988194
TI  - Profile of U.S. radiologists at middecade: overview of findings from the 1995
      survey of radiologists.
AB  - PURPOSE: To profile the demographic, professional, and practice characteristics
      of diagnostic radiologists and radiation oncologists in the United States.
      MATERIALS AND METHODS: Questionnaires mailed to a national stratified random
      sample of 3,024 diagnostic radiologists, radiation oncologists, and nuclear
      medicine specialists yielded a 75% response rate. Weighted data reflect what
      responses would be if all radiologists had been surveyed and had responded.
      RESULTS: Among professionally active, posttraining radiologists in 1995, 14% were
      women; 12% were radiation oncologists, 62% diagnostic generalists, and 26%
      diagnostic subspecialists; 92% were board certified in radiology; 48% had
      postresidency fellowship training; 69% were in a position where practice
      ownership was a potential, and of these, 80% were practice owners. Enjoyment of
      work was less the greater the perceived effect of managed care on a radiologists
      practice, but average work satisfaction was unchanged from 1990. Among
      radiologists aged 55 years or older, the percentage who were retired was
      unchanged from 1990. Average hours worked by professionally active radiologists
      aged 65 years or older increased since 1990. CONCLUSION: Despite the spread of
      managed care and other trends that affect radiologists, surprisingly, few changes
      were evident in the demographic or professional characteristics of U.S.
      radiologists in 1995 compared with 1990.

PMID- 8988195
TI  - Elastography of breast lesions: initial clinical results.
AB  - PURPOSE: To determine the appearance of various breast lesions on elastograms and
      to explore the potential of elastography in the diagnosis of breast lesions.
      MATERIALS AND METHODS: A total of 46 breast lesions were examined with
      elastography. Patients underwent biopsy or aspiration of all lesions, revealing
      15 fibroadenomas, 12 carcinomas, six fibrocystic nodules, and 13 other lesions.
      The elastogram was generated from radio-frequency data collected with use of a 5
      MHz linear-array transducer. The elastogram and corresponding sonogram were
      evaluated by a single observer for lesion visualization, relative brightness, and
      margin definition and regularity. The sizes of the lesions at each imaging
      examination and at biopsy were recorded and compared. RESULTS: Softer tissues
      such as fat appear as bright areas on elastograms. Firm tissues, including
      parenchyma, cancers, and other masses, appear darker. The cancers were
      statistically significantly darker than fibroadenomas (P < .005) and
      substantially larger on the elastogram than on the sonogram. Seventy-three
      percent of fibroadenomas and 56% of solid benign lesions could be distinguished
      from cancers by using lesion brightness and size difference. Some cancers that
      appeared as areas of shadowing on sonograms appeared as discrete masses on
      elastograms. CONCLUSION: Elastography has the potential to be useful in the
      evaluation of areas of shadowing on the sonogram. It also may be helpful in the
      distinction of benign from malignant masses.

PMID- 8988196
TI  - Breast neoplasms: T2* susceptibility-contrast, first-pass perfusion MR imaging.
AB  - PURPOSE: To evaluate the differentiation of benign from malignant breast tumors
      with T2*-weighted perfusion magnetic resonance (MR) imaging (blood volume
      imaging) versus that with dynamic T1-weighted contrast agent-enhanced MR imaging.
      MATERIALS AND METHODS: Ten healthy adult volunteers and 18 adult patients with
      benign or malignant lesions underwent both conventional T1-weighted dynamic
      contrast-enhanced breast MR imaging and repetitive first-pass, single-section,
      dynamic T2*-weighted perfusion MR imaging. Images were obtained before, during,
      and after injection of 20 mL of gadopentetate dimeglumine; peak gadopentetate
      dimeglumine concentrations were calculated from the maximal signal intensity loss
      on T2*-weighted images. RESULTS: No perfusion effect was detectable in healthy
      breast parenchyma. A strong susceptibility-mediated signal intensity loss
      occurred in malignant breast tumors. No or only minor perfusion effects were seen
      in fibroadenomas, in spite of their rapid enhancement at T1-weighted dynamic
      imaging. Perfusion imaging was possible after conventional dynamic contrast
      enhanced breast MR imaging. CONCLUSION: T2*-weighted perfusion imaging exploits
      the susceptibility-mediated signal intensity loss of a first-pass bolus of
      gadopentetate dimeglumine within the capillary bed. First-pass perfusion imaging
      of breast lesions is feasible. It is promising in the differentiation of benign
      from malignant, rapidly enhancing lesions.

PMID- 8988197
TI  - Transthoracic needle biopsy of small pulmonary nodules.
AB  - PURPOSE: To evaluate the diagnostic accuracy, complications, and usefulness of
      transthoracic needle biopsy of small pulmonary nodules. MATERIALS AND METHODS:
      Between January 1993 and January 1995, 302 patients underwent transthoracic
      needle biopsy of pulmonary lesions. Sixty-four lesions (in 62 patients)
      represented small nodules, defined as lesions of 15 mm or less maximum diameter.
      A total of 75 biopsies were performed in the 64 lesions. Approximately 90% of the
      biopsies were performed with computed tomographic guidance. RESULTS: There were
      21 benign lesions and 43 cancers (36 primary, seven metastatic). Transthoracic
      needle biopsy findings were positive for cancer in 40 cases. In all three false
      negative lesions, only one biopsy was performed. There were 21 true-negative
      results and no false-positive results. Positive and negative predictive values
      were 100% and 88%, respectively. Pneumothorax occurred in 20 (27%) of 75
      biopsies, but chest tube placement was necessary in only three cases (4%).
      Surgery or thoracoscopy was avoided in 31 patients: 17 of 20 patients with benign
      disease, seven patients with metastatic disease, and seven patients with
      inoperable lung cancer. CONCLUSION: Transthoracic needle biopsy of small
      pulmonary nodules can produce diagnostic yields comparable with published results
      of transthoracic needle biopsy of larger lesions.

PMID- 8988198
TI  - Small pulmonary lesions detected at CT: clinical importance.
AB  - PURPOSE: To evaluate the histopathologic findings of pulmonary nodules 1 cm or
      smaller detected at computed tomography (CT) that were removed at video-assisted
      thorascopic surgery. MATERIALS AND METHODS: Clinical, radiologic, and
      histopathologic findings were retrospectively reviewed in 64 patients (48 women,
      16 men; aged 22-85 years) who underwent video-assisted thorascopic surgical
      resection of small pulmonary lesions present on CT scans. RESULTS: Sixty-four
      patients had a total of 65 lesions resected. Of the 64 patients, 37 (58%)
      patients had no known previous malignancy and 27 (42%) had previous malignancy.
      Overall, 58% (38 of 65 [95% confidence interval = 0.45, 0.73]) of these lesions
      were malignant. Among the patients without previous malignancy, 14 (38%) had lung
      carcinoma (10 [27%], primary bronchogenic carcinoma; four [11%], carcinoid). In
      patients with a previous malignancy, malignant lesions were diagnosed in 81% (22
      of 27). This included seven (26%) patients with bronchogenic carcinoma as a
      second primary carcinoma. In patients without previous malignancy, benign lesions
      were diagnosed in 59% (22 of 37); in patients with previous malignancy, benign
      lesions were diagnosed in 18% (five of 27). CONCLUSION: A considerable number of
      the malignant lesions were primary bronchogenic carcinoma. In addition, diagnosis
      in patients with a previous malignancy other than suspected metastatic disease
      can substantially alter treatment. For these reasons, early biopsy with an
      acceptable technique for diagnosis of these lesions is recommended.

PMID- 8988199
TI  - Quality control phantom for digital chest radiography.
AB  - PURPOSE: To develop and test a chest phantom for routine quality control testing
      of digital radiography systems. MATERIALS AND METHODS: The phantom was
      constructed from sheets of copper, aluminum, and acrylic, which were cut and
      arranged to yield a radiographic projection resembling that of a human thorax.
      Regional test objects allowed quantitative assessment of optical density,
      contrast detail, and spatial resolution. Validation tests were performed to
      assess image stability in a stable imaging environment and sensitivity to changes
      in image quality when they occur. RESULTS: The phantom yielded consistent
      pseudoclinical images when used in a routine quality control program and
      facilitated detection of simulated problems that were induced in imaging system
      performance. CONCLUSION: The chest phantom enables quantitative, full-system
      testing of digital radiography system as they are used clinically for chest
      radiography.

PMID- 8988200
TI  - Simulation of subtle lung nodules in projection chest radiography.
AB  - PURPOSE: To measure the radiologic characteristics of subtle lung nodules and
      develop nodule phantoms that simulate these characteristics. MATERIALS AND
      METHODS: From a database of chest radiographs, 16 radiographs that showed
      confirmed subtle lung nodules were selected. The optical density values
      surrounding each nodule were obtained, and the radiologic characteristic of the
      nodules were evaluated. A set of Teflon nodule phantoms with similar x-ray
      transmission and variability was designed and fabricated. The contrast
      characteristics of the images of the nodule phantoms were measured. RESULTS: Most
      of the subtle nodules appeared to have diffuse edges with Gaussian-like contrast
      profiles. The contrast and size characteristics of the nodule phantom images
      fulfilled the design criteria within a 4% deviation. CONCLUSION: The radiologic
      pattern of subtle lung nodules is poorly simulated by nodule phantoms with simple
      spherical or disk shapes. The nodule phantoms in this study produce realistic
      radiographic patterns with an energy-dependent attenuation equivalent to that of
      tissue. The nodule phantoms are intended for use in experiments involving human
      subjects.

PMID- 8988201
TI  - Amplitude Doppler US: slow blood flow detection tested with a flow phantom.
AB  - PURPOSE: To evaluate the in vitro sensitivity for the detection of slow blood
      flow in tiny tubes with an amplitude Doppler ultrasound (US) technique at
      different angles and pulse repetition frequencies. MATERIALS AND METHODS: Human
      blood treated with heparin was pumped through silicone tubes (flow phantoms made
      by the author) with lumina of 3.00 mm, 0.30 mm, and 0.05 mm. Slow flow was imaged
      by using amplitude and color Doppler US techniques with two US devices at
      different pulse repetition frequencies and angles and in different sound
      propagation media. RESULTS: Under ideal conditions, the lowest detectable
      velocity was 0.04-0.06 cm/sec in the 3.00-mm tube. Detection was about three to
      four times less sensitive in the 0.30-mm and 0.05-mm tubes. Amplitude Doppler US
      sensitivity is only slightly dependent on the angle of incidence and propagation
      medium. CONCLUSION: The fractional volume flow determined the sensitivity of the
      amplitude Doppler technique for detecting low flow. Amplitude Doppler US is
      nearly angle independent; thus, it is superior to color Doppler US. Amplitude
      Doppler US is three to four times more sensitive when tube have very tiny lumina
      and when probes of a lower frequency are used.

PMID- 8988202
TI  - Definition of liver tumors in the presence of diffuse liver disease: comparison
      of findings at MR imaging with positive and negative contrast agents.
AB  - PURPOSE: The potential to define liver tumors at magnetic resonance (MR) imaging
      was compared with a positive and a negative contrast agent (gadoxetic acid
      disodium, or gadolinium EOB-DTPA [a hepatocyte-directed agent], and ferumoxides,
      or superpara-magnetic iron oxide particles [a Kupffer cell-directed agent],
      respectively) in normal rats and in rats with induced acute hepatitis, fatty
      liver, or cirrhosis. MATERIALS AND METHODS: Rats with implanted liver
      adenocarcinomas were divided into four groups: no diffuse liver disease ("normal"
      [n = 6]) and diffuse liver diseases (induced acute hepatitis [n = 6], fatty liver
      [n = 6], or cirrhosis [n = 6]). Rats first received gadoxetic acid disodium (50
      mumol/kg) and then, 45 minutes later, ferumoxides (10 mumol/kg). Liver signal
      intensity enhancement and tumor-to-liver contrast-to-noise ratio (C/N) were
      measured in each group. RESULTS: Mean liver signal intensity enhancement values
      with gadoxetic acid disodium and ferumoxides were excellent in the normal liver
      model (176% and -62%, respectively; P < .01) but were significantly reduced in
      the acute hepatitis model (82% and -36%, respectively). In the fatty livers
      compared with the normal livers, enhancement with gadoxetic acid disodium was
      reduced (57%) but with ferumoxides was excellent (-55%). In the cirrhotic livers
      compared with the normal livers, enhancement with gadoxetic acid disodium (174%)
      was virtually the same but was impaired with ferumoxides (-43%). CONCLUSION:
      Hepatic enhancement and tumor-to-liver C/N with either positive or negative liver
      enhancing agents can be impaired by the presence of underlying liver disease.
      Prior knowledge of the type of diffuse liver disease may influence the choice of
      contrast agent for tumor detection.

PMID- 8988203
TI  - Helical CT technique for the diagnosis of appendicitis: prospective evaluation of
      a focused appendix CT examination.
AB  - PURPOSE: To evaluate a focused, helical computed tomographic (CT) technique for
      imaging the appendix in patients suspected of having appendicitis. MATERIALS AND
      METHODS: One hundred patients prospectively underwent appendix CT examination,
      with use of oral and colon contrast media and contiguous, thin-collimation,
      helical CT imaging of the right lower quadrant. Results were correlated with the
      results of surgery and pathologic examination from 61 patients or from clinical
      follow-up in 39 patients. RESULTS: CT scans were positive for appendicitis in 59
      patients: true-positive in 56 patients on the basis of surgery and pathologic
      examination, and false-positive in two patients on the basis of clinical follow
      up; in the case of the other positive scan, the clinical outcome was
      indeterminate. CT scans were negative for appendicitis in 41 patients: true
      negative in five patients on the basis of surgery and pathologic examination, and
      true-negative in 36 patients on the basis of clinical follow-up. CT had a
      sensitivity of 100%, a specificity of 95%, a positive predictive value of 97%, a
      negative predictive value of 100%, and an accuracy of 98%. The normal appendix
      was always identified. CT helped establish alternative diagnoses in 33 of the 41
      patients (80%) in whom the results of CT were negative for appendicitis.
      CONCLUSION: Appendix CT examination can help diagnose or exclude appendicitis and
      establish an alternative diagnosis.

PMID- 8988204
TI  - CT diagnosis of mesenteric adenitis.
AB  - PURPOSE: To quantify how frequently mesenteric adenitis clinically mimics
      appendicitis and to determine its appearance at computed tomography (CT).
      MATERIALS AND METHODS: The medical records of 651 consecutive patients with an
      admission diagnosis of appendicitis were reviewed to determine how often
      mesenteric adenitis was the discharge diagnosis. The CT scans of a separate group
      of 18 patients with a discharge diagnosis of mesenteric adenitis were reviewed.
      These patients were part of a group of 100 consecutive patients prospectively
      evaluated with CT of the appendix for clinically suspected appendicitis. RESULTS:
      Fifty of 651 patients (7.7%) with an admission diagnosis of appendicitis had a
      discharge diagnosis of mesenteric adenitis. Mesenteric adenitis constituted 50 of
      the 252 (19.8%) discharge diagnoses other than appendicitis. All 18 CT scans of
      mesenteric adenitis showed three or more nodes that measured at least 5 mm in
      shortest axis clustered in the right lower quadrant, with a normal appendix
      identified. Eight patients had associated ileal or ileocecal wall thickening.
      CONCLUSION: Mesenteric adenitis is an important clinical mimic of appendicitis.
      It appears at CT as clustered, enlarged mesenteric lymph nodes with a normal
      appendix, and there may be associated ileitis or ileocolitis noted.

PMID- 8988205
TI  - Distinguishing small hepatic hemangiomas from vascular liver metastases in
      gastrinoma: use of a somatostatin-receptor scintigraphic agent.
AB  - PURPOSE: To compare somatostatin-receptor scintigraphy and conventional imaging
      modalities in the differentiation of small hepatic hemangiomas from small liver
      metastases in Zollinger-Ellison syndrome. MATERIALS AND METHODS: Twenty-nine
      patients had hypervascular liver lesions smaller than 2 cm that could have been
      either metastases or hemangiomas. Fourteen patients had metastases, 14 had
      hemangiomas, and one had both. Scintigraphy was compared with computed tomography
      (CT), magnetic resonance (MR) imaging, and angiography for the correct
      identification of the lesions. RESULTS: The hemangiomas and liver metastases both
      had a mean size of 1.3 cm. In the patients with hepatic hemangiomas, scintigraphy
      showed no lesions. CT, angiography, or MR imaging showed a lesion in 40%-93%.
      With metastases present, any liver lesion was detected in 93% with scintigraphy
      versus 20%-60% with another modality. Scintigraphy depicted liver metastases in
      93% of patients, which was higher than the sensitivities of other modalities. The
      accuracy (96%) and positive (100%) and negative (93%) predictive values of
      scintigraphy for detecting liver metastases were superior to those of other
      modalities. There were 45 liver metastases and 31 hemangiomas; a per lesion
      analysis gave results similar to the per patient analysis results. CONCLUSION: In
      Zollinger-Ellison syndrome, somatostatin-receptor scintigraphy provides an
      excellent diagnostic tool to differentiate small hepatic hemangiomas from small
      liver metastases.

PMID- 8988206
TI  - Focal hepatic lesions: effect of three-dimensional wavelet compression on
      detection at CT.
AB  - PURPOSE: To evaluate the effect of three-dimensional, wavelet-based compression
      on the detection of focal hepatic lesions at computed tomography (CT). MATERIALS
      AND METHODS: CT images obtained in 69 patients with focal hepatic lesions were
      studied (35 consecutive cases and 34 cases selected to be difficult on the basis
      of lesion size or contrast). Image data were compressed by means of a three
      dimensional, wavelet-based algorIthm at ratios of 10:1, 15:1, and 20:1. Normal
      and abnormal sections (on original and compressed images) were reviewed by using
      an interactive workstation. Four readers rated the presence or absence of a
      lesion with a five-point scale. RESULTS: At receiver operating characteristic
      analysis, no statistically significant difference was detected for all cases
      considered together. Differences approached but did not reach statistical
      significance for the diagnostic performance of one reader with compressed images
      (15:1, P = .054; 20:1, P = .051). For the subset of difficult cases, a
      significant difference was observed with 20:1 compressed images for one reader (P
      = .026). Diagnostic performance of readers was less certain in normal than in
      abnormal cases with both original and compressed images (difference was
      significant for 15:1 [P = .035] and 20:1 [P < .0001] compressed images).
      CONCLUSION: Three-dimensional wavelet compression is satisfactory at ratios of at
      least 10:1. Additional studies with a larger sample would help confirm findings
      with higher ratios.

PMID- 8988207
TI  - Splenic hemangiomas and hamartomas: MR imaging characteristics of 28 lesions.
AB  - PURPOSE: To determine the magnetic resonance (MR) imaging features of splenic
      hemangiomas and hamartomas, including their pattern of dynamic contrast material
      enhancement. MATERIALS AND METHODS: The appearance of 28 lesions in 18 patients
      was retrospectively reviewed on T2-weighted images (16 patients), unenhanced T1
      weighted images (18 patients), and dynamic contrast-enhanced T1-weighted images
      (17 patients). Seventeen of 23 hemangiomas and all five hamartomas were proved at
      pathologic examination. RESULTS: Of the 22 hemangiomas imaged with T2-weighting,
      19 were hyperintense, two were isointense, and one was hypointense relative to
      the spleen. Dynamic gadolinium-enhanced imaging demonstrated a progressive
      centripetal pattern of enhancement in 19 of 22 hemangiomas. On delayed images, 19
      hemangiomas demonstrated uniform enhancement. Of the five hamartomas, four were
      imaged with T2-weighting; three were hyperintense and one was hypointense
      relative to the spleen. All hamartomas demonstrated diffuse heterogeneous
      enhancement on images obtained early after administration of contrast material
      and became more uniformly enhanced on delayed images. CONCLUSION: Splenic
      hemangiomas showed signal intensity characteristics and enhancement patterns
      similar to those described for hepatic hemangiomas. Since these features have
      been shown to reliably distinguish hemangiomas from other benign and malignant
      liver lesions, it may be reasonable to consider without histologic verification
      that lesions in the spleen with these imaging features represent hemangiomas.

PMID- 8988208
TI  - Splenic lymphangiomatosis in children.
AB  - PURPOSE: To study the clinical and imaging features of splenic lymphangiomatosis.
      MATERIALS AND METHODS: The clinical and abdominal imaging data of 10 children
      with splenic lymphangiomatosis were retrospectively reviewed. The modalities used
      in the study included computed tomography (CT) (10 patients), sonography (five
      patients), and magnetic resonance (MR) imaging (two patients). Pathologic
      confirmation of lymphangiomatosis was obtained in nine patients. RESULTS: Splenic
      lymphangiomatosis was discovered incidentally in all cases and was a key finding
      in enabling the correct diagnosis in six children with extrasplenic disease as
      well. Only two children had clinical splenomegaly. Sonograms and MR images showed
      multiple, wEll-defined cysts. Multiple, low-attenuation lesions that did not
      enhance with intravenous administration of contrast material (n = 8) or a mottled
      spleen (n = 2) were seen at CT. One of the mottled spleens had target lesions on
      an early (arterial) image obtained after administration of a bolus of contrast
      material. One child underwent a splenectomy; one child underwent therapeutic
      embolization. Eight patients remained asymptomatic with respect to the spleen 1
      20 years later. CONCLUSION: Splenic lymphangiomatosis is often an incidental
      imaging finding that frequently has a characteristic imaging appearance. The
      recognition of this appearance helps in diagnosis of this disease and may prevent
      the need for further invasive procedures. Splenic changes can be isolated or can
      coexist with bone or soft-tissue lymphangiomas.

PMID- 8988209
TI  - Suppression of venous signal in time-of-flight MR angiography of the lower
      extremities after administration of gadopentetate dimeglumine.
AB  - PURPOSE: To evaluate a magnetic resonance (MR) angiography time-of-flight
      technique that can effectively suppress venous signal after gadopentetate
      dimeglumine administration. MATERIALS AND METHODS: Twelve adult patients
      underwent MR angiography for the evaluation of peripheral vascular disease.
      Gradient-echo sequences were performed after the administration of 0.2 mmol/kg
      gadopentetate dimeglumine. Three sequences were compared: a nontriggered
      sequence; a gap sequence, an electrocardiographically triggered, segmented
      sequence with a 7-mm gap between saturation and imaging sections; and a no-gap
      sequence, a similar sequence as gap but with partially overlapping imaging and
      saturation sections. For each sequence, identical regions of interest were
      generated for arterial, venous, and background muscle tissue and noise. A paired
      Student t test was used to compare the signal-to-noise and contrast-to-noise
      ratios (C/Ns) among the sequences. In seven patients, the no-gap sequence was
      used to acquire MR angiograms of the distal lower extremities. RESULTS: The mean
      artery-muscle C/N was similar for the triggered sequences; both were
      statistically significantly greater than the ratios for the nontriggered
      sequence. Venous suppression was much better with the no-gap sequence. Overall,
      the best artery-vein C/N was also obtained with the no-gap sequence. MR
      angiograms with effective venous suppression could be obtained only with the no
      gap sequence. CONCLUSION: Time-of-flight MR angiograms can be obtained with
      effective venous suppression after the administration of 0.2 mmol/kg
      gadopentetate dimeglumine.

PMID- 8988210
TI  - Thoracic aorta: comparison of gadolinium-enhanced three-dimensional MR
      angiography with conventional MR imaging.
AB  - PURPOSE: To evaluate gadolinium-enhanced three-dimensional magnetic resonance
      (MR) angiography for thoracic aortic disease and to compare this technique with
      conventional thoracic MR imaging. MATERIALS AND METHODS: One hundred eight
      consecutive patients underwent 122 thoracic MR examinations, including
      conventional MR imaging followed by enhanced three-dimensional MR angiography. A
      gradient-echo sequence was used at 1.5 T (116 examinations) and 1.0 T (6
      examinations) during infusion of 0.2 mmol/kg gadopentetate dimeglumine. Two
      independent readers (A and B), with varied experience in thoracic MR angiography,
      retrospectively evaluated the images for presence of aortic dissection, aneurysm,
      arch vessel disease, and protruding atheroma. Correlation with findings of
      surgery or other imaging modalities was available in 98 cases. RESULTS: Enhanced
      MR angiography was sensitive (92%-96%) and specific (100%) for acute and chronic
      aortic dissection (n = 26) and was as useful as conventional MR imaging in the
      diagnosis of aneurysm (n = 43) and arch vessel disease (n = 7). One of two
      intramural hematomas were overlooked at MR angiography by reader A, and both were
      overlooked by reader B. CONCLUSION: Enhanced three-dimensional MR angiography is
      a rapid and accurate imaging modality in diagnosis of thoracic aortic disease but
      is insensitive to intramural hematoma.

PMID- 8988211
TI  - Percutaneous US-guided radio-frequency tissue ablation of liver metastases:
      treatment and follow-up in 16 patients.
AB  - PURPOSE: To determine the potential efficacy of radio-frequency (RF) ablation of
      liver metastases during long-term follow-up. MATERIALS AND METHODS: Sixteen
      patients with 31 hepatic metastases were treated with percutaneous, ultrasound
      guided RF ablation. RF was applied to monopolar electrodes (2-3-cm tip exposure)
      either individually or within a multiprobe array (two to four probes) for 6
      minutes at 90 degrees C over one to four treatment sessions per metastasis.
      RESULTS: In only one of 75 sessions, a moderate complication, self-limited
      intraperitoneal hemorrhage, was observed. Four patients (four lesions) underwent
      surgical resection 15-60 days after RF treatment. Residual, viable tumor was seen
      in all of these patients. The remaining 12 patients were followed up for 9-29
      months (mean, 18.1 months). In these patients, 18 of 27 lesions remained stable
      or decreased in size and showed no enhancement at computed tomography and/or
      magnetic resonance imaging for at least 9 months. Two patients died of
      disseminated disease at 13 months and one at 16 months. Disease-free survival was
      achieved in eight patients. CONCLUSIONS: RF ablation appears to be a simple,
      safe, and potentially effective treatment for selected patients with liver
      metastases and may become a less invasive alternative to surgical therapy.

PMID- 8988212
TI  - Saline-enhanced radio-frequency tissue ablation in the treatment of liver
      metastases.
AB  - PURPOSE: To assess the effect of intraparenchymal saline injection on the results
      of radio-frequency (RF) tissue ablation. MATERIALS AND METHODS: Ex vivo and in
      vivo animal RF ablation was performed with and without intraparenchymal saline
      injection. Initially, saline was injected as a bolus (1-20 mL) before RF
      application. For subsequent in vivo studies, saline was injected as a bolus
      before RF application or continuously (1 mL/min) during RF application. Finally,
      14 patients with liver metastases and one patient with primary cholangiocarcinoma
      were treated with the continuous infusion technique. A single RF electrode (tip
      exposure, 1-3 cm) was used with various ablation parameters. RESULTS: With
      pretreatment bolus injection of saline, lesions measured 1.4 cm +/- 0.1, 1.6 cm
      +/- 0.2, and 1.2 cm +/- 0.1 in ex vivo liver, in vivo animal muscle, and in vivo
      animal liver, respectively. Without saline enhancement, lesion sizes were 1.0 +/-
      0.2, 1.2 +/- 0.2, and 0.8 +/- 0.1 cm, respectively. With continuous saline
      injection in in vivo pig liver, lesion size was 1.8 - 4.1 cm in diameter. In
      human tumors, necrosis volume was variable, but complete necrosis was seen in 13
      of 25 lesions (diameter, 1.2-3.9 cm). Partial necrosis greater than 50% was seen
      in 12 lesions (diameter, 1.5-4.5 cm). CONCLUSION: Saline-enhanced RF ablation
      might permit percutaneous destruction of large liver lesions.

PMID- 8988213
TI  - Multiphasic helical CT of the kidney: increased conspicuity for detection and
      characterization of small (< 3-cm) renal masses.
AB  - PURPOSE: To evaluate the potential of thin-section multiphasic helical computed
      tomography (CT) in the detection and characterization of small (< 3.0-cm) renal
      masses. MATERIALS AND METHODS: Identically collimated helical CT of the kidney
      was performed before and after administration of contrast material in 93 patients
      with small renal masses. Helical CT scans were obtained during the
      corticomedullary and nephrographic phases. Differences between attenuation of the
      lesion and that of the kidney were measured quantitatively. The presence of a
      mass or absence of disease was confirmed with clinical, imaging, and histologic
      findings. RESULTS: The number of masses smaller than 3.0 cm detected on
      corticomedullary-phase scans (n = 211) was statistically significantly fewer than
      those on nephrographic-phase scans (n = 295) (P < .01). Mean differences in
      enhancement between the renal cortex and masses were 148 HU +/- 54 and 137 HU +/-
      44 during the corticomedullary and nephrographic phases, respectively, and the
      difference in attenuation of the renal medulla and that of the masses was
      statistically significantly greater during the nephrographic phase (P < .01).
      False-positive results (n = 9) occurred only on corticomedullary-phase scans
      because of lack of enhancement of the renal medulla. CONCLUSION: Nephrographic
      phase scans enabled greater lesion detection and better characterization of small
      renal masses than corticomedullary-phase scans. Nephrographic-phase scans should
      be obtained when only monophasic scanning is used to detect small renal masses.

PMID- 8988214
TI  - Staging prostate cancer with MR imaging: a combined radiologist-computer system.
AB  - PURPOSE: To test the accuracy of a combined radiologist-computer system in the
      diagnosis with magnetic resonance (MR) imaging of cancer of the prostate gland.
      MATERIALS AND METHODS: The combined system was developed and tested by four
      specialists in prostate MR imaging and five radiologists expert in body MR
      imaging. Each group read MR images obtained in 100 proved cases of prostate
      cancer. The images were obtained from two sources, and all were obtained with an
      endorectal surface coil. Prostate MR specialists ranked imaging features of cases
      to develop a checklist for image interpretation. Features with greatest
      diagnostic value were incorporated in the combined system. Accuracy measures were
      derived from the area index of the receiver operating characteristic curve for
      the combined system and compared with those of radiologists working alone.
      RESULTS: Body MR radiologists had a mean baseline accuracy of 0.67; mean accuracy
      of their combined system was 0.80. The prostate MR specialists, when they rated
      the features in each case, had a mean accuracy of 0.81; the accuracy of their
      combined system was 0.87. CONCLUSIONS: A combined radiologist-computer system
      substantially improved accuracy of body MR radiologists in the diagnosis of
      prostate cancer. High levels of accuracy were also achieved by the system with
      prostate MR specialists.

PMID- 8988215
TI  - Pheochromocytoma: effect of nonionic contrast medium in CT on circulating
      catecholamine levels.
AB  - PURPOSE: To study the catecholamine-releasing effect of peripheral intravenous
      administration of the nonionic contrast medium iohexol in patients with
      pheochromocytomas. MATERIALS AND METHODS: Ten patients (eight women, two men;
      mean age, 44 years; age range, 25-70 years) with pheochromocytomas and related
      tumors and six healthy volunteers (five men, one woman; mean age, 31 years; age
      range, 27-35 years) were examined. Plasma catecholamine levels were measured at
      intervals for 60 minutes after the injection of 0.9% saline or iohexol on 2
      separate days. All 10 patients intravenously received the specific alpha
      adrenergic blocker phenoxybenzamine hydrochloride (0.5 mg/kg in 250 mL of 5%
      dextrose infused over 2 hours) 24 hours before iohexol-enhanced computed
      tomography. RESULTS: There was no statistically significant increase in
      epinephrine or norepinephrine levels in the patients or the control subjects.
      CONCLUSION: While it may be prudent to administer oral alpha- and beta
      adrenoceptor antagonists in all patients with a biochemically proved
      pheochromocytoma to control their symptoms and to prevent a spontaneous
      adrenergic crisis, specific blockade may not be required before contrast medium
      enhanced scanning with iohexol. Although the sample size of this study is
      relatively small, the results do suggest that in an incidentally detected,
      clinically silent adrenal mass that may or may not be hypersecreting, the
      nonionic contrast medium iohexol may be used for scanning without blockade.

PMID- 8988216
TI  - Laser ablation-induced changes in the prostate: findings at endorectal MR imaging
      with histologic correlation.
AB  - PURPOSE: To correlate laser ablation-induced changes in the prostate as depicted
      at endorectal magnetic resonance (MR) imaging with results at histologic
      examination. MATERIALS AND METHODS: In eight patients with prostate carcinoma,
      visually guided laser ablation was performed during lymphadenectomy. Radical
      prostate resection was performed 4-9 days (mean, 6.9 days) after ablation in
      seven patients and at 70 days in one patient. The study protocol consisted of (a)
      endorectal T2-weighted fast spin-echo imaging, (b) dynamic T1-weighted spoiled
      gradient-echo imaging prior to and after injection of contrast material, and (c)
      gadolinium-enhanced T1-weighted spin-echo imaging. Imaging findings were
      correlated with macroscopic and histologic findings. RESULTS: Histologic
      examination revealed periurethral necrosis with a marginal zone that consisted of
      partially necrotic tissue, dilated vessels, and hemorrhagic areas. Considerable
      interindividual difference was observed in the extent of morphologic alterations
      (area, 0-18.0 cm3). Gadolinium-enhanced images were best suited for assessment of
      laser ablation-induced changes. The correlation between the volume of altered
      tissue measured on MR images and in macroscopic specimens was excellent (r2 =
      .96). CONCLUSION: MR imaging helped monitor changes induced with laser ablation
      (which differed greatly among individuals). MR monitoring may thus be useful in
      patients with obstructive benign prostatic hyperplasia after laser ablation.

PMID- 8988217
TI  - CT and MR imaging in the local staging of primary malignant musculoskeletal
      neoplasms: Report of the Radiology Diagnostic Oncology Group.
AB  - PURPOSE: To assess the relative accuracies of computed tomography (CT) and
      magnetic resonance (MR) imaging in the local staging of primary malignant bone
      and soft-tissue tumors. MATERIALS AND METHODS: At four institutions, 367 eligible
      patients (aged 6-89 years) with malignant bone or soft-tissue neoplasms in
      selected anatomic sites were enrolled. Patients underwent both CT and MR imaging
      within 4 weeks before surgery. In each patient, CT scans were interpreted
      independently by two radiologists and MR images by two other radiologists at the
      enrolling institution. The CT and MR images were then interpreted together by two
      of those radiologists and subsequently reread at the other institutions. Imaging
      and histopathologic findings were compared and were supplemented when needed with
      surgical findings. Receiver operating characteristic curve analysis and
      descriptive statistical analysis were performed. RESULTS: Cases were analyzable
      in 316 patients: 183 had primary bone tumors; 133 had primary soft-tissue tumors.
      There was no statistically significant difference between CT and MR imaging in
      determining tumor involvement of muscle, bone, joints, or neurovascular
      structures. The combined interpretation of CT and MR images did not statistically
      significantly improve accuracy. Interreader variability was similar for both
      modalities. CONCLUSION: CT and MR imaging are equally accurate in the local
      staging of malignant bone and soft-tissue neoplasms in the specific anatomic
      sites studied.

PMID- 8988218
TI  - Nonmyelomatous monoclonal gammopathy: correlation of bone marrow MR images with
      laboratory findings and spontaneous clinical outcome.
AB  - PURPOSE: To determine the frequency of abnormal bone marrow magnetic resonance
      (MR) images in patients with nonmyelomatous monoclonal gammopathy and to compare
      the outcomes in patients with normal and in those with abnormal MR studies.
      MATERIALS AND METHODS: In 37 patients with monoclonal gammopathy of undetermined
      or borderline significance (19 men, 18 women; aged 28-85 years), MR imaging
      findings of the vertebral, pelvic, and femoral bone marrow were analyzed and
      correlated with initial laboratory findings and outcome after a follow-up of 15
      60 months (median, 31 months) with no treatment. RESULTS: Thirty patients had
      normal MR studies; none required specific therapy after a median follow-up of 30
      months. Seven had either diffuse (n = 4) or focal (n = 3) bone marrow
      abnormalities. Four required treatment after 15, 20, 50, or 58 months; three did
      not require treatment after 18, 26, or 40 months. Treatment-free survival curves
      in patients with normal and in those with abnormal MR studies were statistically
      significantly different (P = .005). CONCLUSION: Bone marrow abnormalities were
      detected with MR imaging in seven patients (19%) with monoclonal gammopathy of
      undetermined or borderline significance. All patients with a normal MR
      investigation still had not required treatment after a median follow-up of 30
      months.

PMID- 8988219
TI  - Cupid's bow contour of the vertebral body: evaluation of pathogenesis with bone
      densitometry and imaging-histopathologic correlation.
AB  - PURPOSE: To investigate the Cupid's bow contour by means of bone densitometry and
      imaging-histopathologic correlation. MATERIALS AND METHODS: Radiographs and
      histologic slices were obtained in 64 cadaveric thoracolumbar spines to assess
      the morphology, distribution, and histopathologic features of the Cupid's bow
      contour. Dual-energy x-ray absorptiometry and radiography were performed in the
      lumbar spine in 406 healthy subjects. Bone density and body height and weight
      were then related to the presence of the Cupid's bow contour. The Cupid's bow
      contour was compared with the fish vertebra of osteoporosis and Schmorl node.
      RESULTS: No clinically important relationship was found between lumbar bone
      density, body height and weight, and prevalence of the Cupid's bow contour.
      Histologic examination showed thickened bone in the Cupid's bow end plate with
      annular fibers inserting into this region. In cadavers, the Cupid's bow contour
      occurred at multiple lumbar and thoracic levels, with the highest frequency in
      the lower lumbar spine. Lateral radiographs enabled better detection of the
      contour change. CONCLUSION: The Cupid's bow deformity is a developmental
      phenomenon that is unrelated to osteopenia or mechanical stress on the spine.

PMID- 8988220
TI  - Mesenteric circulation: three-dimensional MR angiography with a gadolinium
      enhanced multiecho gradient-echo technique.
AB  - To evaluate the mesenteric circulation with magnetic resonance (MR) angiography,
      the authors examined 16 individuals (12 patients, four volunteers) with a
      gadolinium-enhanced, breath-hold, fat-saturated, multiecho, three-dimensional,
      gradient-echo sequence. Twenty examinations were performed. Grades of 3 or 4 (on
      a five-point scale [4 = best seen, 0 = not seen]) were applicable to 17 (85%) of
      20 MR angiograms obtained in superior mesenteric artery trunks, 15 (75%) in
      celiac arteries, five (25%) in inferior mesenteric arteries; 15 (75%) of first
      order branching, 12 (60%) of second-order branching, and 10 (50%) of third-order
      branching; 17 (85%) in superior mesenteric veins; and 17 (85%) in portal veins.
      MR angiography with this technique depicted the mesenteric arterial and venous
      circulation and the portal vein with excellent resolution in a short time.

PMID- 8988221
TI  - Total-body MR imaging in as little as 18 seconds.
AB  - Eighteen human subjects underwent echo-planar magnetic resonance (MR) imaging of
      the whole body at 1.5 T. A stack of axial images was obtained from the top of the
      head to the feet with gradient-echo, spin-echo, and inversion-recovery spin-echo
      pulse sequences by moving the patient table through the magnet isocenter. In all
      examinations, the subjects tolerated the procedure well and table motion was
      uniform. Image quality depended on careful setting of the transmit frequency,
      gain, and shims. Results were easily obtained and reproducible in all cases in as
      little as 18 seconds.

PMID- 8988222
TI  - Hepatic arterial-phase dynamic gadolinium-enhanced MR imaging: optimization with
      a test examination and a power injector.
AB  - To optimize findings at dynamic gadolinium-enhanced hepatic magnetic resonance
      imaging in the hepatic arterial phase, a timing examination was performed after
      injection of a 0.5-mL timing bolus of gadopentetate dimeglumine. In the
      experimental group (n = 28), power injection was used and the imaging delay was
      determined in each patient on the basis of the results of the timing examination.
      In the control group (n = 28), hand injection and a fixed 20-second imaging delay
      were used. Arterial-phase examinations (defined as relative liver enhancement of
      not more than 30% of peak parenchymal enhancement) were successful in 26 (93%)
      experimental group patients and in 17 (61%) control group patients.

PMID- 8988223
TI  - MR-guided endovascular interventions: susceptibility-based catheter and near-real
      time imaging technique.
AB  - In a 47-year-old healthy male volunteer, susceptibility-based magnetic resonance
      (MR) imaging was performed in the basilic vein in the right upper arm at 1.5 T. A
      conventional 3-F nonbraided polyethylene catheter with a 0.3-mm lumen diameter
      was locally impregnated with dysprosium oxide, and six ringed areas of increased
      susceptibility were created. passive tracking of the catheter was performed with
      near-real-time conventional two-dimensional gradient-echo angiography. The entire
      prepared part of the catheter was depicted without steering problems or
      complications. Passive tracking is expected to provide a valuable adjunct to
      active tracking for guiding endovascular interventions.

PMID- 8988224
TI  - Transjugular intrahepatic portosystemic shunts: assessment with helical CT
      angiography.
AB  - To evaluate diagnostic computed tomographic (CT) angiograms of transjugular
      intrahepatic portosystemic shunts (TIPS), helical CT angiography was performed in
      10 patients with (n = 7) or without (n = 3) shunt dysfunction. CT angiography was
      performed with 3-mm-thick sections, pitch of 1, 120 kV, and 180-220 mA, after
      injection of 150 mL nonionic contrast material at 5 mL/sec, with a 50-second
      scanning delay after initiation of injection. All patients underwent transjugular
      portography within 1 week after CT angiography. In all cases, CT angiography
      correctly showed the presence or absence of the abnormality. These preliminary
      data suggest that CT angiography can provide diagnostic images of normal and
      abnormal TIPS.

PMID- 8988225
TI  - Endotracheal placement of balloon-expanded stents: an experimental study in
      rabbits.
AB  - The authors implanted balloon-expanded stents in the trachea of 10 rabbits for 1
      day to 6 months. Follow-up included chest radiography, clinical examination,
      light microscopy, and scanning electron microscopy. Pneumothorax occurred in two
      cases after placement, marked stridor due to mucus plugging in all cases, signs
      of infection in three cases (two of which developed into pneumonitis),
      compression of the upper stent end in two cases, and moderate to severe mucus
      plugging in all cases. Microscopically, none of the stents was completely covered
      with epithelium even at 6 months. The high rate of complications may be a result
      of the rigid construction, which does not allow tracheal movement or adaptation
      of the stent shape to the shape of the trachea.

PMID- 8988226
TI  - Depiction of the cisterna chyli at CT.

PMID- 8988227
TI  - Gain setting in power Doppler US.

PMID- 8988228
TI  - Disease of the supraaortic branches: spiral CT versus MR imaging.

PMID- 8988229
TI  - Normal levels of DM RNA and myotonin protein kinase in skeletal muscle from adult
      myotonic dystrophy (DM) patients.
AB  - A major question about the pathogenesis of myotonic dystrophy (DM) is how the
      (CTG)n repeat mutation alters expression of the DM gene and how that is related
      to disease causation. Most previous studies have found a decrease in DM RNA and
      protein in patient tissue. In contrast to these reports we find, unexpectedly,
      that independent of the size of the CTG repeat: (1) there are equal levels of RNA
      products of mutant and normal alleles, and (2) levels of Mt-PK in skeletal muscle
      from DM patients is unaltered from normal. These findings are consistent with the
      recent hypothesis that mutant DM DNA or RNA may cause disease by disrupting the
      function of other, yet unidentified, genes.

PMID- 8988230
TI  - Detection of a novel splice-site mutation that results in skipping exon 3 of the
      WASP gene in a patient with Wiskott-Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is one of the primary immunodeficiency diseases,
      that is inherited as an X-linked recessive trait. Since the responsible gene, the
      WASP gene, has been identified, various mutations for patients with WAS have been
      reported. We found a novel splice-site mutation in a patient with clinically
      diagnosed WAS. The mutation was a replacement of ag by aa in an acceptor site of
      intron 2 of the WASP gene. Sequencing studies of the WASP cDNA of the patient
      revealed that exon 3 of the WASP gene was abnormally missing due to a splicing
      defect.

PMID- 8988231
TI  - Structural and functional characterization of three human immunoglobulin kappa
      light chains with different pathological implications.
AB  - The structural properties of three immunoglobulins light chains: kappa SCI,
      responsible for light chain deposition disease (Bellotti, V., Stoppini, M.,
      Merlini, G., Zapponi, M.C., Meloni, M.L., Banfi, G. and Ferri, G. (1991) Biochim.
      Biophys. Acta 1097, 177-182), k INC responsible for light chain amyloidosis
      (Ferri, G., Stoppini, M., Iadarola, P., Bellotti, V. and Merlini, G. (1989)
      Biochim. Biophys. Acta 995, 103-108) and the non-pathogenic kappa MOS were
      analyzed by fluorescence spectroscopy and circular dichroism. Comparative
      evaluation of the data shows that SCI and MOS have similar stability under
      different conditions, while the amyloid k INC behaves as a very unstable protein.
      As calculated from the GdnHCl curves, the midpoint of unfolding transition was
      1.35 M for SCI, 1.20 M for MOS and 0.1 M for INC. Analysis of CD spectra
      evidences that the three proteins conserve their conformation in the range of pH
      4-8. Change in temperature at pH 4.0 produces the premature transition of INC (Tm
      40 degrees C) with respect to SCI and MOS (Tm 50 degrees C). At this pH both the
      pathological SCI and INC light chains aggregate at a temperature of 20 degrees C
      lower than the normal counterpart. The specific kidney deposition of kappa SCI
      has been evidenced after injection of the 125I labelled light chain into mice. No
      deposition was detectable in the case of INC and MOS.

PMID- 8988232
TI  - Inhibition of human TNF alpha and LT in cell-free extracts and in cell culture by
      antisense oligonucleotides.
AB  - Antisense oligonucleotides (ODN), complementary to mRNA of human tumor necrosis
      factor alpha (TNF alpha) and lymphotoxin (LT) were tested for their ability to
      inhibit TNFs. TNFs production was studied in cell-free systems including wheat
      germ extract (WGE) and rabbit reticulocyte lysate (RRL). All ODN were effective
      in WGE at low concentration (0.2 microM), except those targeted to the 3' region
      of TNF alpha mRNA. A short ODN complementary to a common region between TNF alpha
      and LT inhibited both TNFs. In contrast, high ODN concentration (50 microM) was
      needed to inhibit LT mRNA translation in RRL, whereas no clear inhibition of TNF
      alpha was observed unless RNase H was added to the translation mixture. ODN
      effects on TNFs production by stimulated cell line in culture were also
      investigated. Three ODN-one located in the 5'-untranslated region, one spanning
      the AUG initiation codon and one downstream of this AUG-were the most effective
      sequences to decrease TNF alpha production. Two ODN targeted to the AUG
      initiation codon of LT were also able to inhibit its production. In conclusion we
      confirm the role of RNase H in cell free systems, and we found that there is no
      correlation between ODN efficiency in a cell-free system nor in cell culture.
      Efficient ODN could be used for in vitro investigation of the role of TNF alpha
      and LT in mechanism in which they are involved.

PMID- 8988233
TI  - Identification and purification of Ca2+/calmodulin-dependent protein kinase V
      from human gastric carcinoma.
AB  - We previously purified a novel Ca2+/calmodulin-dependent protein kinase (CaM
      kinase) V, which has proven to be a member of the CaM kinase I family.
      Immunohistochemical staining of surgically-resected specimens from human subjects
      using specific antibody which reacts with CaM kinases I and V demonstrated
      heterogeneous distribution of CaM kinase I/V in normal gastric mucosa. The kinase
      was located mainly at the bottom of foveoral epithelium and in the gastric gland
      (< 25% immunopositive). In contrast, this kinase was abundant in various types of
      gastric carcinomas (> 75%), but not in gastric adenomas. Preferential and
      consistent presence of this kinase was confirmed by immunoblot analysis of
      gastric carcinoma and human gastric cancer cell lines, Kato-III and MKN-45. CaM
      kinase I/V was co-purified with CaM kinase II from resected gastric carcinoma
      using anion-exchange chromatography followed by calmodulin-affinity
      chromatography. The two kinases were finally separated by HPLC-based gel
      filtration. Purified CaM kinase I/V from gastric carcinoma did not possess
      detectable autophosphorylating activity, in contrast to CaM kinase II. The
      findings suggest CaM kinase I/V may possess abnormal biochemical properties in
      human gastric carcinoma, and the kinase could participate in cell growth of the
      carcinoma.

PMID- 8988235
TI  - Decreased plasma carnitine and trimethyl-L-lysine levels associated with
      lysosomal accumulation of a trimethyl-L-lysine containing protein in Batten
      disease.
AB  - Batten disease, or juvenile neuronal ceroid-lipofuscinosis, is an autosomal
      recessive hereditary disorder that leads to blindness, severe neurological
      degeneration, and premature death. The disease is characterized by massive
      accumulation of lysosomal storage bodies in most tissues. A significant
      constituent of the storage material is a protein that appears to be almost
      identical to a small hydrophobic inner mitochondrial membrane protein, subunit c
      of ATP synthase. The protein isolated from the storage bodies contains an epsilon
      N-trimethyl-L-lysine (TML) residue at amino acid position 43. The presence of TML
      in the stored protein suggests that one of the lysine residues in subunit c is
      normally trimethylated, and this trimethylation may act as a signal to initiate
      degradation of the protein. Free TML produced by the degradation of TML
      containing proteins is the first intermediate in the carnitine biosynthetic
      pathway. It is possible that trimethylated subunit c is a major source of the
      free TML used in carnitine biosynthesis. If this is the case, one would predict
      that the genetic defect resulting in the accumulation of TML containing subunit c
      would also reduce systemic levels of free TML and carnitine. To evaluate this
      possibility, plasma TML and carnitine levels were measured in affected human
      subjects, heterozygous carriers, and normal controls. Both TML and carnitine
      levels were significantly depressed in the affected individuals. This suggests
      that subunit c is normally a major source of TML for carnitine biosynthesis. In
      Batten disease, failure to degrade the TML-containing form of subunit c is
      probably responsible for the reduction in plasma TML and carnitine levels.

PMID- 8988234
TI  - A common structural motif in immunopotentiating peptides with sequences present
      in human autoantigens. Elicitation of a response mediated by monocytes and Th1
      cells.
AB  - We have found a common structural motif in human autoantigens, heat shock
      proteins and viral proteins. Peptides modelled after sequences present in those
      molecules were synthesized and immunomodulating properties tested. They share a
      core of 15 amino acid residues and a common pattern ('2-6-11' motif)
      characterized by requirements at fixed positions with respect to a Pro (position
      6); an apolar residue or a Lys at position 2; and a Glu, Asp or Lys at position
      11. Any of these peptides, when added to cultures of lymphomononuclear cells,
      caused the activation of monocytes manifested by a release of IL-1 alpha, IL-1
      beta and TNF alpha. A release of INF gamma and IL-2 took also place; this release
      was abolished by anti-DR antibodies. Neither IL-4 nor IL-5 could be detected.
      This suggests a presentation by APCs and the appearance of cells with a Th1
      phenotype. Monocytes and Th1 cells freshly obtained from 12 patients of Graves'
      disease, 8 of Hashimoto's disease and 8 of primary biliary cirrhosis exhibited
      activation features similar to those found in cells from healthy subjects
      incubated in the presence of peptides with a "2-6-11' motif and representing
      fragments of autoantigens. Their immunopotentiating properties suggest their
      involvement in the initiation or progression of the autoimmune response mediated
      by activated monocytes and Th1 cells.

PMID- 8988236
TI  - Antimycin resistance and ubiquinol cytochrome c reductase instability associated
      with a human cytochrome b mutation.
AB  - Progressive exercise intolerance was associated with a decreased maximal rate of
      ubiquinol cytochrome c reductase (complex III) activity in the muscle
      mitochondria of the studied patient and with a thirty five-fold increase in the
      I50 for antimycin A. In contrast, myxothiazol sensitivity was not altered.
      Complex III activity was stable at 37 degrees C, but progressively decreased at 4
      degrees C. An heteroplasmic G to A mutation at position 15615 of the
      mitochondrial DNA, resulting in the replacement of the highly conserved Gly290 in
      cytochrome b by Asp, was identified. Histochemical studies showed increased
      cytochrome oxidase and succinate dehydrogenase activities under the sarcolemma of
      type I fibres. After partial extraction of mitochondria from the muscle, the
      residual pellet contained a lower percentage of the mutation than did whole
      muscle, suggesting that the percentage of mutation is higher in the most readily
      extracted mitochondria, most probably present under the sarcolemma. In the
      current 8 transmembrane helix model of cytochrome b, Gly290 lies at the end of
      the sixth transmembrane helix, facing the intermembrane space and close to the
      presumed sites of interaction between cytochrome b, the iron-sulfur protein and
      the 9.5 kDa protein. Since immunoblotting experiments showed a relative decrease
      in the proportions of these three subunits in the patient's mitochondria compared
      with the other complex III subunits, it is probable that the complex III
      instability and the relative decrease in these subunits are related to the
      mutation. The relationship between the decrease in the apparent affinity for
      antimycin A and the instability of complex III are discussed.

PMID- 8988237
TI  - Biochemical properties of acetyl- and butyrylcholinesterase in human meningioma.
AB  - The structural properties of acetyl-(AChE) and butyrylcholinesterase (BuChE) in
      meningioma and the possible relationship with brain and plasma were investigated.
      Meningioma ChEs were extracted with saline and saline-Triton X-100 buffers. The
      tumor ChE forms were identified by sedimentation analysis, and their
      amphiphilic/hydrophilic behaviour was assessed by Triton X-114 phase-partitioning
      and hydrophobic chromatography. Meningioma contained amphiphilic globular AChE
      dimers (G2A) and monomers (G1A), and hydrophilic BuChE tetramers (G4H). The
      conversion of G2A into G1A AChE by reduction confirmed their structures. In
      contrast to the meningioma species, brain G1A AChE forms remained amphiphilic
      after incubation with alkaline hydroxylamine and phosphatidylinositol-specific
      phospholipase C (PIPLC). Meningioma G1A and PIPLC-converted G1H, and brain G1A
      AChE showed similar rate constants for thermal inactivation, and this suggested
      that the thermal stability of AChE subunits was unaffected by the presence or not
      of phosphatidylinositol residues. AChE in meningioma and brain did not differ in
      the interaction with the lectins Con A, LCA, WGA and RCA. BuChE in meningioma and
      brain bound to a similar extent to Con A, LCA and WGA-Agarose, whereas one-half
      of BuChE in the tumor, all in plasma and little in brain was fixed by RCA.
      Therefore, meningioma possesses RCA(+)- and RCA(-)-BuChE, the former
      predominating in brain and the latter in plasma. It remains to be clarified
      whether the tumor RCA(+)-BuChE is intrinsic or derived from plasma.

PMID- 8988238
TI  - Plasma tumor necrosis factor-a (TNF-a) levels in Gaucher disease.
AB  - Tumor necrosis factor-a (TNF-a) levels were measured in the plasma of patients
      with different types of Gaucher disease (GD) and patients with other lysosomal
      storage diseases. The highest TNF-a levels were observed in the most severe
      neuronopathic type of GD, exceeding those found in healthy individuals as well as
      patients with other lysosomal disorders. Type I GD cases showed a wide range of
      TNF-a levels ranging from normal to 2.5 x the highest control value. TNF-a is a
      pleiotropic cytokine produced mainly by activated macrophages. Our data suggest
      that it may play a role in the pathophysiology of GD disease.

PMID- 8988239
TI  - Identification of regulatory sequences in the promoter of the PDGF B-chain gene
      in malignant mesothelioma cell lines.
AB  - Platelet-derived growth factor (PDGF) B-chain mRNA is readily detectable in
      malignant mesothelioma (MM) cell lines, but not in normal mesothelial (NM) cell
      lines. The high affinity receptor for PDGF B-chain dimers, the PDGF beta
      receptor, is expressed in MM cell lines. NM cell lines predominantly express the
      PDGF alpha-receptor. Coexpression of the PDGF beta-receptor and its ligand may
      lead to an autocrine growth stimulating loop in the malignant cell type. In
      nuclear run off experiments, PDGF B-chain mRNA was detectable in MM cells only,
      indicating an increased level of transcription in this cell type. The proximal
      promoter of the PDGF B-chain gene contains DNaseI hypersensitive (DH) sites and
      mediates reporter gene activation in both normal and malignant cells. Nuclear
      proteins, extracted from both cell types, interact with DNA sequences within the
      proximal promoter around bp-64 to -61 relative to the transcription start site.
      Electrophoretic mobility shift assays (EMSAs) indicate that these factors are
      more abundantly present in the malignant than in the normal cell type. A DH site
      around -9.9 kb was found in both cell types. When tested in CAT assays, this
      region exerted a stimulatory effect on transcription in malignant cells. The
      elevated level of transcription of the PDGF B-chain gene in malignant cells may
      well be the result of interaction of regulatory sites in the proximal promoter
      and an enhancing element located at -9.9 kb from the transcription start site.

PMID- 8988240
TI  - Selective endocytosis of fluorothymidine and azidothymidine coupled to LDL into
      HIV infected mononuclear cells.
AB  - Drug targeting via lipoproteins may be of benefit for use of cytotoxic drugs like
      fluorothymidine (FLT) or azidothymidine (AZT). Both drugs are potent inhibitors
      of the human immunodeficiency virus (HIV) reverse transcriptase and are used in
      the therapy of HIV infection. With regard to this project, the selective
      endocytosis in HIV infected human macrophages was studied after covalent coupling
      of AZT and LDL to low density lipoproteins (LDL). Cultured human macrophages and
      the lymphocytic Molt 4/8 cell line were infected with HIV-1 in vitro and
      subsequently treated with FLT-LDL or AZT-LDL. Viral replication was followed by
      determination of cell-released capsid antigen p24. Internalisation into HIV-1
      infected human macrophages by the scavenger receptor pathway leads to a dose
      dependent inhibition of HIV replication. Otherwise, in HIV infected, but
      scavenger receptor missing lymphocytes (Molt 4/8 cells), neither endocytosis nor
      inhibition of HIV replication results. Thus, covalent coupling of drugs to LDL
      leads to a macrophage specific transport. This strategy could possibly avoid
      toxic side effects in the therapeutic use of antiretroviral drugs and thus may
      open a way for an earlier chemotherapy in HIV infection.

PMID- 8988241
TI  - Molecular machinery mediating vesicle budding, docking and fusion.
AB  - A general machinery buds and fuses transport vesicles which connect intracellular
      compartments with each other and allow communication with the extracellular
      environment. Cytoplasmic coat proteins deform membranes to bud vesicles and
      interact directly or indirectly with cargo molecules. Compartment-specific SNAREs
      (SNAP receptors) on vesicles and target membranes dock vesicles and provide a
      scaffolding for the general fusion machinery to initiate lipid bilayer fusion.

PMID- 8988242
TI  - Bacterial protein toxins and cell vesicle trafficking.
AB  - A group of bacterial protein toxins interfere with vesicular trafficking inside
      cells. Clostridial neurotoxins affect mainly the highly regulated fusion of
      neurotransmitter- and hormone-containing vesicles with the plasma membrane. They
      cleave the three SNARE proteins: VAMP, SNAP-25 and syntaxin, and this selective
      proteolysis results in a blockade of exocytosis. The Helicobacter pylori
      cytotoxin is implicated in the pathogenesis of gastroduodenal ulcers. It causes a
      progressive and extensive vacuolation of cells followed by necrosis, after a
      cytotoxin-induced alteration of membrane trafficking by late endosomes. Vacuoles
      originate from this compartment in a rab7-dependent process and swell because
      they are acidic and accumulate membrane-permeant amines.

PMID- 8988243
TI  - Actin-, myosin- and ubiquitin-dependent endocytosis.
AB  - Endocytosis is a general term that is used to describe the internalization of
      external and plasma membrane molecules into the cell interior. In fact, several
      different mechanisms exist for the internalization step of this process. In this
      review we emphasize the work on the actin-dependent pathways, in particular in
      the yeast Saccharomyces cerevisiae, because several components of the molecular
      machinery are identified. In this yeast, the analysis of endocytosis in various
      mutants reveals a requirement for actin, calmodulin, a type I myosin, as well as
      a number of other proteins that affect actin dynamics. Some of these proteins
      have homology to proteins in animal cells that are believed to be involved in
      endocytosis. In addition, the demonstration that ubiquitination of some cell
      surface molecules is required for their efficient internalization is described.
      We compare the actin, myosin and ubiquitin requirements for endocytosis with
      recent results found studying these processes using Dictyostelium discoideum and
      animal cells.

PMID- 8988244
TI  - Polypeptide translocation machinery of the yeast endoplasmic reticulum.
AB  - Proteins enter the secretory pathway by two general routes. In one, the complete
      polypeptide is made in the cytoplasm and held in an incompletely folded state by
      chaperoning adenosine triphosphatases (ATPases) such as hsp70. In Saccharomyces
      cerevisiae, fully synthesized secretory precursors engage the endoplasmic
      reticulum (ER) membrane by interaction with a set of Sec proteins comprising the
      polypeptide translocation apparatus (Sec61p, Sec62p, Sec63p, Sec71p, Sec72p).
      Productive interaction requires displacement of hsp70 from the precursor, a
      reaction that is facilitated by Ydj1p, a homologue of the Escherichia coli DnaJ
      protein. Both DnaJ and Ydj1p regulate chaperone activity by stimulating the
      ATPase activity of their respective hsp70 partners (E. coli DnaK and S.
      cerevisiae Ssa1p, respectively). In the ER lumen, another hsp70 chaperone, BiP,
      binds ATP and interacts with the ER membrane via its contact with a peptide loop
      of Sec63p. This loop represents yet another DnaJ homologue in that it contains a
      region of approximately 70 residue similarity to the 'J box', the most conserved
      region of the DnaJ family of proteins. In the presence of ATP, under conditions
      in which BiP can bind to Sec63p, the secretory precursor passes from the cytosol
      into the lumen through a membrane channel formed by Sec61p. A second route to the
      membrane pore that is used by many other secretory precursors, particularly in
      mammalian cells, requires that the polypeptide engage the ER membrane as the
      nascent chain emerges from the ribosome. Such cotranslational translocation
      bypasses the need for certain Sec proteins, instead utilizing an alternate set of
      cytosolic and membrane factors that allows the nascent chain to be inserted
      directly into the Sec61p channel.

PMID- 8988245
TI  - The cytosolic and membrane components required for peroxisomal protein import.
AB  - Peroxisomes are vital intracellular organelles which house enzymes involved in a
      variety of metabolic pathways. The large number of human disorders associated
      with flawed peroxisome biogenesis emphasizes the importance of protein targeting
      to, and translocation across, the peroxisomal membrane. This brief review will
      summarize some of the emerging themes of peroxisomal protein import, specifically
      addressing the targeting signals possessed by constituent proteins, as well as
      the cytosolic, membrane and luminal components of the import machinery. Although
      a detailed understanding of the molecular mechanisms of peroxisomal protein
      import is not yet available, remarkable progress has been made in the field in
      recent years. An overview of these advances will be presented.

PMID- 8988246
TI  - In vitro systems in the study of peroxisomal protein import.
AB  - Our level of understanding of peroxisome biogenesis in comparison with other
      cellular organelles is rudimentary, yet the fragments of information available
      indicate that the targeting and import of peroxisomal proteins occur by
      fundamentally different mechanisms. Genetic studies have identified a number of
      genes required for peroxisome assembly, but in most cases the functions of the
      gene products remain unknown. In vitro protein translocation systems have played
      a prominent role in unravelling the biochemistry of protein translocation into
      other organelles. This review considers some of the requirements for establishing
      a bona fide peroxisomal import assay and discusses the findings which have
      emerged as a result of using such experimental systems.

PMID- 8988247
TI  - Cytosolic factors in mitochondrial protein import.
AB  - In vitro import studies have confirmed the participation of cytosolic protein
      factors in the import of various precursor proteins into mitochondria. The
      requirement for extramitochondrial adenosine triphosphate for the import of a
      group of precursor proteins seems to be correlated with the chaperone activity of
      the cytosolic protein factors. One of the cytosolic protein factors is hsp70,
      which generally recognizes and binds unfolded proteins in the cytoplasm. Hsp70
      keeps the newly synthesized mitochondrial precursor proteins in import-competent
      unfolded conformations. Another cytosolic protein factor that has been
      characterized is mitochondrial import stimulation factor (MSF), which seems to be
      specific to mitochondrial precursor proteins. MSF recognizes the mitochondrial
      precursor proteins, forms a complex with them and targets them to the receptors
      on the outer surface of mitochondria.

PMID- 8988248
TI  - Regulated protein degradation in mitochondria.
AB  - Various adenosine triphosphate (ATP)-dependent proteases were identified within
      mitochondria which mediate selective mitochondrial protein degradation and
      fulfill crucial functions in mitochondrial biogenesis. The matrix-localized PIM1
      protease, a homologue of the Escherichia coli Lon protease, is required for
      respiration and maintenance of mitochondrial genome integrity. Degradation of non
      native polypeptides by PIM1 protease depends on the chaperone activity of the
      mitochondrial Hsp70 system, posing intriguing questions about the relation
      between the proteolytic system and the folding machinery in mitochondria. The
      mitochondrial inner membrane harbors two ATP-dependent metallopeptidases, the m-
      and the i-AAA protease, which expose their catalytic sites to opposite membrane
      surfaces and cooperate in the degradation of inner membrane proteins. In addition
      to its proteolytic activity, the m-AAA protease has chaperone-like activity
      during the assembly of respiratory and ATP-synthase complexes. It constitutes a
      quality control system in the inner membrane for membrane-embedded protein
      complexes.

PMID- 8988249
TI  - The mitochondrial processing peptidase: function and specificity.
AB  - Targeting signals of mitochondrial precursors are cleaved in the matrix during or
      after import by the mitochondrial processing peptidase (MPP). This enzyme
      consists of two nonidentical alpha- and beta-subunits each of molecular weight of
      about 50 kDa. In mammals and fungi, MPP is soluble in the matrix, whereas in
      plants the enzyme is part of the cytochrome bc1 complex. MPP is a
      metalloendopeptidase which has been classified as a member of the pitrilysin
      family on the basis of the HXXEHX76E zinc-binding motif present in beta-MPP. Both
      subunits of MPP are required for processing activity. The alpha-subunit of MPP,
      which probably recognizes a three-dimensional motif adopted by the presequence,
      presents the presequence to beta-MPP, which carries the catalytic active site.
      MPP acts as an endoprotease on chemically synthesized peptides corresponding to
      mitochondrial presequences. Matrix-targeting signals and MPP cleavage signals
      seem to be distinct, although the two signals may overlap within a given
      presequence. The structural element helix-turn-helix, that cleavable presequences
      adopt in a membrane mimetic environment, may be required for processing but is
      not sufficient for proteolysis. Binding of the presequence by alpha-MPP tolerates
      a high degree of mutations of the presequence. alpha-MPP may present a
      degenerated cleavage site motif to beta-MPP in an accessible conformation for
      processing. The conformation of mitochondrial presequences bound to MPP remains
      largely unknown.

PMID- 8988250
TI  - Allosteric proteins after thirty years: the binding and state functions of the
      neuronal alpha 7 nicotinic acetylcholine receptors.
AB  - A key statement of the 1965 Monod-Wyman-Changeux (MWC) model for allosteric
      proteins concerns the distinction between the ligand-binding function (Y) and the
      relevant state function (R). Sequential models predict overlapping behavior of
      the two functions. In contrast, a straightforward experimental consequence of the
      MWC model is that for an oligomeric protein the parameters which characterize the
      two functions should differ significantly. Two situations, where R > Y and the
      system is hyper-responsive or where R < Y and the system is hypo-responsive, have
      been encountered. Indeed, the hyper-responsive pattern was first observed for the
      enzyme aspartate transcarbamoylase, by comparing Y with R monitored by a change
      in sedimentation. Extensions of the theory to ligand-gated channels led to the
      suggestion that, on the one hand, hyper-responsive properties also occur with
      high-affinity mutants. On the other hand, native channels of the acetylcholine
      neuronal alpha 7 receptor and low-affinity mutants of the glycine receptor can be
      interpreted in terms of the hypo-responsive pattern. For the ligand-gated
      channels, whereas R is detected directly by ion flux, ligand binding has rarely
      been measured and the formation of desensitized states may complicate the
      analysis. However, stochastic models incorporating both binding and channel
      opening for single molecules predict differences that should be measurable with
      new experimental approaches, particularly fluorescence correlation spectroscopy.

PMID- 8988251
TI  - The plasma membrane calcium pump: recent developments and future perspectives.
AB  - The Ca2+ pump of the plasma membrane (PMCA) is regulated by a number of agents.
      The most important is calmodulin (CaM), which binds to a domain located in the C
      terminal portion of the pump, removing it from an autoinhibitory site next to the
      active site. The CaM-binding domain is preceded by an acidic sequence which
      contains a hidden signal for endoplasmic reticulum (ER) retention. Chimeras of
      the PMCA and endoplasmic reticulum (SERCA) pumps have revealed the presence of a
      strong signal for ER retention in the first 45 residues of the SERCA pump. Four
      gene products of the PMCA pump are known: two of them (1 and 4) are ubiquitously
      expressed, two (2 and 3) are specific for nerve cells and may be induced by their
      activation. Mutagenesis work has identified four residues in three of the
      transmembrane domains of the pump which may be components of the trans-protein
      Ca2+ path. The mutation of two of these residues alters the membrane targeting of
      the pump.

PMID- 8988252
TI  - Vacuolar H(+)-ATPase: from mammals to yeast and back.
AB  - Vacuolar H(+)-adenosine triphosphatase (V-ATPase) is composed of distinct
      catalytic (V1) and membrane (V0) sectors containing several subunits. The
      biochemistry of the enzyme was mainly studied in organelles from mammalian cells
      such as chromaffin granules and clathrin-coated vesicles. Subsequently, mammalian
      cDNAs and yeast genes encoding subunits of V-ATPase were cloned and sequenced.
      The sequence information revealed the relation between V- and F-ATPase that
      evolved from a common ancestor. The isolation of yeast genes encoding subunits of
      V-ATPase opened an avenue for molecular biology studies of the enzyme. Because V
      ATPase is present in every known eukaryotic cell and provides energy for vital
      transport systems, it was anticipated that disruption of genes encoding V-ATPase
      subunits would be lethal. Fortunately, yeast cells can survive the absence of V
      ATPase by 'drinking' the acidic medium. So far only yeast cells have been shown
      to be viable without an active V-ATPase. In contrast to yeast, mammalian cells
      may have more than one gene encoding each of the subunits of the enzyme. Some of
      these genes encode tissue- and/or organelle-specific subunits. Expression of
      these specific cDNAs in yeast cells may reveal their unique functions in
      mammalian cells. Following the route from mammals to yeast and back may prove
      useful in the study of many other complicated processes.

PMID- 8988253
TI  - Mitochondrial distribution and inheritance.
AB  - Mechanisms mediating the inheritance of mitochondria are poorly understood, but
      recent studies with the yeasts Saccharomyces cerevisiae and Schizosaccharomyces
      pombe have begun to identify components that facilitate this essential process.
      These components have been identified through the analysis of conditional yeast
      mutants that display aberrant mitochondrial distribution at restrictive
      conditions. The analysis of these mutants has uncovered several novel proteins
      that are localized either to cytoskeletal structures or to the mitochondria
      themselves. Many mitochondrial inheritance mutants also show altered
      mitochondrial morphology and defects in maintenance of the mitochondrial genome.
      Although some inheritance components and mechanisms appear to function
      specifically in certain types of cells, other conserved proteins are likely to
      mediate mitochondrial behavior in all eukaryotic cells.

PMID- 8988254
TI  - Actin-based organelle movement.
AB  - Evidence for actin-dependent organelle movement was first obtained from studies
      of cytoplasmic streaming in plants. These studies, together with cell-free
      organelle motility studies and biophysical analyses of muscle myosin, support a
      model whereby organelle-associated motor molecules utilize the energy of
      adenosine triphosphate binding and hydrolysis to drive movement along F-actin
      tracks. Recent studies indicate that this mechanism for organelle movement may be
      responsible for organelle and vesicle movement during secretion, endocytosis and
      mitochondrial inheritance in a variety of eukaryotes.

PMID- 8988255
TI  - Myc: a single gene controls both proliferation and apoptosis in mammalian cells.
AB  - c-myc was discovered as the cellular homologue of the transduced oncogene of
      several avian retroviruses. The gene encodes a transcription factor, which forms
      a heteromeric protein complex with a partner protein termed Max. In mammalian
      cells, Myc is a central regulator of cell proliferation and links external
      signals to the cell cycle machinery. Myc also induces cells to undergo apoptosis,
      unless specific signals provided either by cytokines or by oncogenes block the
      apoptotic pathway. Recent progress sheds light both on the factors regulating the
      function and expression of Myc and on the downstream targets in the cell cycle.
      Together, these findings suggest the existence of a novel signal transduction
      pathway regulating both apoptosis and proliferation.

PMID- 8988256
TI  - Translational control of endogenous and recoded nuclear genes in yeast
      mitochondria: regulation and membrane targeting.
AB  - Mitochondrial gene expression in yeast, Saccharomyces cerevisiae, depends on
      translational activation of individual mRNAs by distinct proteins encoded in the
      nucleus. These unclearly coded mRNA-specific translational activators are bound
      to the inner membrane and function to mediate the interaction between mRNAs and
      mitochondrial ribosomes. This complex system, found to date only in organelles,
      appears to be an adaptation for targeting the synthesis of mitochondrially coded
      integral membrane proteins to the membrane. In addition, mRNA-specific
      translational activation is a rate-limiting step used to modulate expression of
      at least one mitochondrial gene in response to environmental conditions. Direct
      study of mitochondrial gene regulation and the targeting of mitochondrially coded
      proteins in vivo will now be possible using synthetic genes inserted into mtDNA
      that encode soluble reporter/passenger proteins.

PMID- 8988259
TI  - Symptoms of DSM-III-R major depression among Anglo, African and Mexican American
      adolescents.
AB  - Ethnocultural differences in the phenomenology of DSM-III-R major depression
      among adolescents was examined in a sample of 334 Anglo, African and Mexican
      American patients 12-17 years of age. Diagnoses were made using the Diagnostic
      Interview Schedule for Children, Version 2.1. Analyses of rates of individual
      symptoms as well as the nine DSM-III-R criteria revealed minimal differences
      among youths in the three ethnic groups who received a diagnosis of major
      depressive disorder. There also were minimal differences between boys and girls
      in symptom profiles.

PMID- 8988258
TI  - Molecular genetics of the peptidyl transferase center and the unusual Var1
      protein in yeast mitochondrial ribosomes.
AB  - Mitochondria possess their own ribosomes responsible for the synthesis of a small
      number of proteins encoded by the mitochondrial genome. In yeast, Saccharomyces
      cerevisiae, the two ribosomal RNAs and a single ribosomal protein, Var1, are
      products of mitochondrial genes, and the remaining approximately 80 ribosomal
      proteins are encoded in the nucleus. The mitochondrial translation system is
      dispensable in yeast, providing an excellent experimental model for the molecular
      genetic analysis of the fundamental properties of ribosomes in general as well as
      adaptations required for the specialized role of ribosomes in mitochondria.
      Recent studies of the peptidyl transferase center, one of the most highly
      conserved functional centers of the ribosome, and the Var1 protein, an unusual
      yet essential protein in the small ribosomal subunit, have provided new insight
      into conserved and divergent features of the mitochondrial ribosome.

PMID- 8988257
TI  - Nuclear organization and transcriptional silencing in yeast.
AB  - Transcriptional repression at the yeast silent mating type loci requires the
      formation of a nucleoprotein complex at specific cis-acting elements called
      silencers, which in turn promotes the binding of a histone-associated Sir-protein
      complex to adjacent chromatin. A similar mechanism of long-range transcriptional
      repression appears to function near telomeric repeat sequences, where it has been
      demonstrated that Sir3p is a limiting factor for the propagation of silencing. A
      combined immunofluorescence/in situ hybridization method for budding yeast was
      developed that maintains the three-dimensional structure of the nucleus. In wild
      type cells the immunostaining of Sir3p, Sir4p and Rap1 colocalizes with Y'
      subtelomeric sequences detected by in situ hybridization. All three antigens and
      the subtelomeric in situ hybridization signals are clustered in foci, which are
      often adjacent to, but not coincident with, nuclear pores. This colocalization of
      Rap1, Sir3p and Sir4p with telomeres is lost in sir mutants, and also when Sir4p
      is overexpressed. To test whether the natural positioning of the two HM loci,
      located roughly 10 and 25 kb from the ends of chromosome III, is important for
      silencer function, a reporter gene flanked by wild-type silencer elements was
      integrated at various internal sites on other yeast chromosomes. We find that
      integration at internal loci situated far from telomeres abrogates the ability of
      silencers to repress the reporter gene. Silencing can be restored by creation of
      a telomere at 13 kb from the reporter construct, or by insertion of 340 bp of
      yeast telomeric repeat sequence at this site without chromosomal truncation.
      Elevation of the internal nuclear pools of Sir1p, Sir3p and Sir4p can relieve the
      lack of repression at the LYS2 locus in an additive manner, suggesting that in
      wild-type cells silencer function is facilitated by its juxtaposition to a pool
      of highly concentrated Sir proteins, such as those created by telomere
      clustering.

PMID- 8988260
TI  - Mental disorders in cancer suicides.
AB  - Mental disorders among suicide victims who had suffered from cancer were
      investigated using psychological autopsy data on all suicides in Finland over 1
      year. Retrospective DSM-III-R consensus diagnoses were assigned to all 60 cancer
      suicides and to 60 age- and sex-matched comparison suicides without a cancer
      history. Depressive syndromes were equally common along cancer suicides (80%) and
      others (82%). Alcohol dependence and personality disorders were more frequent
      among noncancer suicides. Major depression and substance abuse were more common
      among victims with cancer in remission than in terminal stages. Only a small
      minority of cancer suicides seem to occur in the absence of mental disorders.

PMID- 8988261
TI  - Clonazepam in acute mania: time-blind evaluation of clinical response and
      concentrations in plasma.
AB  - This study was performed to evaluate the optimal doses and clinical efficacy of
      clonazepam as a first-line drug in acute mania, as well as to determine its
      effective plasma concentrations. Clonazepam was administered orally to 11 newly
      admitted inpatients. On day 0, the loading dose was titrated upward according to
      the clinical global impression; the maintenance dose was calculated with intent
      to maintain the plasma level that had been achieved after initial dose
      escalation. Clinically based dose adjustments were allowed on days 4 and 7. Manic
      symptoms were scored on days 0, 4 and 14 according to a time-blind procedure;
      clonazepam plasma levels were measured by HPLC. On day 14, there was a
      significant decrease in manic symptoms and 66.7% of the patients who completed
      the trial were markedly improved. Steady-state plasma levels of clonazepam were
      significantly correlated with daily doses (rs = 0.795, P < 0.005) and therapeutic
      concentrations ranged between 6.5-83.9 micrograms/l. At the onset of therapy, the
      clinically titrated loading dose resulted in plasma concentrations within the
      narrow range of 18.9-34.0 micrograms/l. These results support the potential value
      of clonazepam in the short-term management of acute mania; the initial control of
      agitation was achieved with plasma drug levels in a remarkably narrow range as
      compared with the further control of mania.

PMID- 8988263
TI  - Circadian variation of plasma cobalamin, transcobalamin-bound cobalamin and
      unsaturated binding capacity of transcobalamin and haptocorrin in healthy
      elderly.
AB  - Blood samples were drawn every second hour during a 24-h period from healthy
      elderly subjects. Plasma levels of cobalamin, albumin, transcobalamin-bound
      cobalamin and unsaturated binding capacity of transcobalamin and haptocorrin were
      determined. During night, all components decreased in parallel with plasma
      albumin. The nocturnal decreases were therefore ascribed to plasma volume changes
      due to bed-rest. Reports on the recently proposed role of cobalamin for the
      biological clock were reviewed, but the proposed role could not be explained by
      this study.

PMID- 8988262
TI  - Increased serum interleukin-1-receptor-antagonist concentrations in major
      depression.
AB  - Recently, it has been shown that major depression may be accompanied by an
      increased production of interleukin-1 beta (IL-1 beta), an acute phase (AP)
      response and simultaneous signs of activation and suppression of cell-mediated
      immunity. The interleukin-1-receptor antagonist (IL-1-rA) is released in vivo
      during an AP response and serum levels are increased in many immune disorders.
      The release of IL-1-rA may limit the pro-inflammatory effects of IL-1. This study
      has been carried out to examine serum IL-1-Ra in 68 depressed subjects (21 minor,
      25 simple major and 22 melancholic subjects) vs. 22 normal controls. Depressed
      subjects showed significantly higher serum IL-1-rA concentrations than healthy
      controls. 29% of all depressed subjects had serum IL-1-rA levels higher than the
      mean value +2 standard deviations of normal controls; 44% depressed subjects had
      IL-1-rA values greater than 0.215 ng/ml with a specificity of 90%. In depressed
      subjects, there was a significant and positive relationship between serum IL-1-rA
      and severity of illness. In depression, there were no significant relationships
      between serum IL-1-rA concentrations and indicants of hypothalamic-pituitary
      adrenal (HPA)-axis activity, such as 24-h urinary cortisol and postdexamethasone
      cortisol values. Women had significantly higher serum IL-1-rA levels than men.
      The findings support the thesis that depression is accompanied by an immune
      inflammatory response.

PMID- 8988264
TI  - Suicide attempts, age and duration of illness in recurrent affective disorders.
AB  - One of the strongest predictors of suicide is a suicide attempt in the history of
      the patient. The question, however, is to what extent age and duration of the
      illness affects the risk of a suicide attempt. In this study, we examined the
      course of 310 patients with primary affective disorders before lithium
      prophylaxis and compared the clinical data of those with and without suicide
      attempts in their history. In a subgroup of 98 patients with suicide attempts,
      measures for both suicide attempts and inpatient episodes were investigated.
      Comparing patients with suicide attempts and those without, we found no
      difference between duration of illness and number of previous episodes between
      the two groups. However, those with a suicide attempt in their history had an
      earlier onset of the illness. In the group of 98 suicide attempters, we found no
      significant correlation between age and rates for both episodes and suicide
      attempts, which indicates that these rates were not declining as the illness
      progressed and the patient aged. Dividing the sample into three different age
      groups, episode rates and rates of attempted suicide were found to be positively
      correlated in all age groups, again indicating that as long as episodes occur,
      the suicide risk does not decline. The results are not in favor of findings which
      suggest that the risk of attempting suicide might manifest itself primarily in
      the early course of the illness or that suicide attempts in the early course of
      illness provide a 'cathartic effect' which leads to a lower risk in the later
      course of the illness. Rather, the findings support the view that the risk of
      suicide attempts in recurrent affective disorders is unchanged in all age groups
      and throughout all stages of untreated illness.

PMID- 8988265
TI  - T-lymphocyte proliferative response to mitogen stimulation in elderly depressed
      patients.
AB  - T-lymphocyte responses to phytohemoagglutinin (PHA) stimulation were examined in
      10 elderly women with nonmelancholic Major Depressive Disorders (MDD), in 10 age-
      and sex-matched controls and in 10 young female controls, before and after in
      vivo stimulation with corticotropin-releasing hormone (CRH). The tests were
      repeated in MDD patients after 30 days of therapy with phosphatidylserine (BC
      PS), 200 mg/day, p.o. T-lymphocyte responses to PHA stimulation did not differ in
      the three groups, and were not changed by CRH administration. BC-PS therapy,
      while significantly improving the depressive symptomatology, did not modify the T
      lymphocyte response to PHA, either before or after CRH stimulation.

PMID- 8988266
TI  - The neuroendocrine response to d-fenfluramine in women with premenstrual
      depression.
AB  - An oral d-fenfluramine neuroendocrine challenge test was carried out in 17 women
      with premenstrual depression and 14 controls, twice in each subject, once in the
      late luteal phase when mood change was likely to be at its worst (i.e.
      premenstrual) and once postmenstrually. Women weighing < 65 kg received 15 mg,
      the remainder 30 mg of d-fenfluramine. Although there was considerable individual
      variability, a substantial average prolactin response was observed in both groups
      but no phase, group or group x phase interaction effects were found. Oestradiol
      levels were significantly higher during the postmenstrual test but showed no
      relationship to prolactin response. Cortisol showed a more modest response to the
      drug and a phase effect was found, with cortisol increase being greater during
      the postmenstrual test in both groups. In contrast to earlier findings with i.v.
      L-tryptophan challenge, the present study failed to show any difference in
      neuroendocrine response between women with premenstrual depression and controls.
      These results suggest that 5-hydroxy-tryptophan2 receptor function is unaltered
      in perimenstrual mood disorder although other interpretations of the negative
      findings are discussed.

PMID- 8988267
TI  - Major and minor depression in later life: a study of prevalence and risk factors.
AB  - In this paper, the results of a community-based study into the prevalence and
      risk factors associated with depression in the older (55-85 years) population of
      The Netherlands are presented. The prevalence of major depression was 2.02%, that
      of minor depression 12.9%, while 14.9% had clinically relevant levels of
      depressive symptoms. Associations with a comprehensive set of risk factors were
      not affected dramatically by age or sex. However, comparing major to minor
      depression, risks were substantially differently distributed. It appears that
      major depression is more often an exacerbation of a chronic mood disturbance,
      with roots in long-standing vulnerability factors; while minor depression is more
      often a reaction to the stresses commonly experienced in later life.

PMID- 8988268
TI  - Annotation: the extraordinary cognitive journey from foetus through infancy.

PMID- 8988269
TI  - The impact of postnatal depression on boys' intellectual development.
AB  - A follow-up study was carried out to investigate the children of 204 mothers who
      had previously participated in a study of their mental health during pregnancy
      and the first postnatal year. One hundred and seventy two children, 170 mothers,
      and 99 fathers were assessed when the children were 3 years 10 months. Boys of
      mothers depressed in the first year postpartum scored approximately 1 standard
      deviation lower on standardised tests of intellectual attainment than boys whose
      mothers were well that year. The difference was reliable even when behaviour
      during the test was controlled for, and general behavioural problems, birth
      weight, parental IQ measures of the family climate and home environment, mother
      child interaction, and breast-feeding during infancy were taken into account.

PMID- 8988270
TI  - Self-perceptions of adolescents with and without mood disorder: content and
      structure.
AB  - This study compared the self-perceptions of three groups of adolescents: one
      group with conduct disorder, a second group comorbid with both mood and conduct
      disorder, and a third group of normal controls. Results indicated that the three
      groups differed on several domains of self-perception, with each group reporting
      perceived strengths and weaknesses. Second-order principal component analyses
      revealed differences across groups in the structure of their self-perceptions.
      Finally, regression analyses indicated that self-perceptions share variance with
      a mixture of internalizing and externalizing symptoms. Results are discussed from
      a clinical-developmental perspective.

PMID- 8988271
TI  - Sibling resemblance for psychiatric disorders in offspring at high and low risk
      for depression.
AB  - This study examined sibling resemblance for major depressive disorder, anxiety
      disorder, and conduct disorder, in offspring at high and low risk for depression
      by virtue of parental diagnosis. The sample, which ranged in age from 6 to 23
      years, included 164 sibling pairs at high risk, and 68 sibling pairs at low risk.
      Each cohort was assessed at two waves separated by a 2-year period. Sibling
      resemblance in the high risk cohort was substantially greater than resemblance in
      the low risk cohort for anxiety disorder (and comorbid conditions including
      anxiety disorder), but not depression. Discussion focused on the possibility that
      anxiety disorder may reflect the most pronounced familial influences common to
      siblings at high risk for depression.

PMID- 8988272
TI  - Follow-up of two-year-olds referred for possible autism.
AB  - Thirty, 2-year-old children referred for possible autism were evaluated using a
      parent interview, a rating scale and psychometric tests and reassessed one year
      later. Clinical diagnosis was relatively stable across time; diagnosis using the
      formal measures changed significantly, particularly for younger and more
      developmentally delayed children. Several patterns contributed to the increasing
      differentiation of children with autism from age 2 to 3, including the
      development of clearly recognizable, repetitive behaviors in the autistic
      children and significant improvements in basic social skills in the children
      judged not to be autistic.

PMID- 8988273
TI  - Treating people as objects, agents, or "subjects": how young children with and
      without autism make requests.
AB  - A procedure previously used to investigate imperative communication in non-human
      primates was applied to young children, some of whom had autism. The goal was to
      examine closely how requests are made in a problem-solving situation. Each
      child's spontaneous strategies to obtain an out-of-reach object were analyzed in
      terms of the ways in which he or she used the adult who was present. Results
      showed that fewer children with autism used a strategy of treating the person as
      a "subject", and that more children with autism used object-centred strategies.

PMID- 8988274
TI  - The identity of mixed parentage adolescents.
AB  - Theories about "black identity" are discussed in relation to a study of
      adolescents with one white and one African or African-Caribbean parent. Interview
      findings on their racial self-definition, attitudes to their mixed parentage, and
      allegiance to black and white people and cultures reveal a wide range of racial
      identities and cultural allegiances. Differences are related to type of school,
      social class, and the degree of politicisation of the young person's attitudes to
      race. The findings are discussed in relation to the issue of interracial adoption
      and fostering, and to recent debates about the concept of an "essential" black
      identity.

PMID- 8988275
TI  - Self-reported and parent reported problems in adolescent international adoptees.
AB  - Self-reported and parent reported problem behaviors of 1,538 intercountry adopted
      adolescents aged 14-18 years were compared with those from general population
      samples; 22% of the adopted boys, and 18% of the adopted girls could be regarded
      deviant according to self-reports, compared with about 10% of the subjects from
      the general population. Parents' reports showed a slightly greater difference
      between adopted versus nonadopted boys. Childhood deprivation was weakly
      associated with later parent reported, but not with self-reported problems.
      Racial antagonism was not related to problem behaviors. Adolescence may
      constitute a period of increased vulnerability for adopted children.

PMID- 8988276
TI  - New reproductive technology and the family: the parent-child relationship
      following in vitro fertilization.
AB  - Parent-child relationships and the parents' psychosocial functioning were
      assessed in families with a 24-30-month-old, single born child conceived by
      homologous in vitro fertilization (IVF) and in a control group of families with a
      naturally conceived child. The investigation included behavioural observations of
      mother-child interactions in the home, and self-rated questionnaires. No
      significant multivariate group effects were found for indicators of the parent
      child relationship, nor for the parents' psychosocial functioning. However, in
      the case of IVF the employment status of the mother was associated with her
      behaviour towards her child: employed IVF-mothers showed less respect for their
      child's autonomy compared with both nonemployed IVF-mothers and employed control
      mothers.

PMID- 8988277
TI  - Problem behavior in early and middle childhood: an initial behavior genetic
      analysis.
AB  - Twin samples were used to estimate the relative importance of genetic and
      environmental influences on problem behavior in children, assessed by the Child
      Behavior Checklist (CBCL). For the younger cohort, mothers completed the CBCL/2
      3, while for the older cohort the CBCL/4-18 was used. Nearly half of the older
      sample had also been assessed with the questionnaire for younger children at a
      prior date, providing tentative answers regarding continuity and change in the
      etiology of problem behavior. Results suggested that shared environmental
      influences may be more important in early childhood than in middle childhood,
      while the reverse holds for genetic influences.

PMID- 8988278
TI  - Performance of children with ADHD on the Rey-Osterrieth complex figure: a pilot
      neuropsychological study.
AB  - This study evaluates the performance of boys with Attention Deficit Hyperactivity
      Disorder (ADHD) on the Rey-Osterrieth Complex Figure (ROCF) taking into
      consideration familiality and comorbid psychiatric and learning disorders (LD).
      Sixty-five children with ADHD performed at developmentally lower levels of Copy
      Organization and Recall Style than did 45 controls. ADHD children with LD scored
      significantly lower on Copy Organization than did ADHD children without LD,
      whereas psychiatric comorbidity and familiality had no effect. These results
      suggest that a developmental analysis of the ROCF identifies organizational
      difficulties associated with ADHD and that these impairments cannot simply be
      attributed to comorbidities associated with ADHD.

PMID- 8988279
TI  - Debate and argument. Who participates in child sexual abuse research?

PMID- 8988280
TI  - Is the Continuous Performance Task useful in research with ADHD children?
      Comments on a review.
AB  - A recent review of the Continuous Performance Task (CPT) as a research tool by
      Corkum and Siegel, Journal of Child Psychology and Psychiatry, 34, 1217-1239,
      1993, is criticized for insufficient covering of the relevant literature,
      disregard of the question of differentiation among clinical groups, and
      inadequacy of explanations of Attention-Deficit-Hyperactivity Disorder (ADHD) in
      terms of arousal, activation, and effort. An attention-deficit in ADHD children
      cannot be inferred from poor performance on a CPT. Impaired performance is
      anything but specific to ADHD children and is caused by a host of variables among
      which "attention" probably plays a minor role.

PMID- 8988281
TI  - Review of the Observer 3.0.

PMID- 8988282
TI  - Physiology of the circadian system in animals and humans.
AB  - Virtually all organisms have developed an internal timing system capable of
      reacting to and anticipating environmental stimuli with a program of
      appropriately timed metabolic, physiologic, and behavioral events. The
      predominant biological rhythms coincide with the geophysical cycle of day and
      night-the circadian rhythms. The suprachiasmatic nuclei comprise the primary pace
      maker in mammals, exhibiting the properties fundamental to a rhythm-generating
      structure. This article summarizes recent research that has elucidated mechanisms
      of signal transduction within the circadian system. The roles of various
      neurochemicals and hormones in transmitting the circadian timing signal are
      described. Properties of the circadian system, including photic and nonphotic
      entrainment, phase response curves, masking, and the intrinsic variability in the
      system are discussed.

PMID- 8988283
TI  - Circadian rhythm sleep disorders: pathophysiology and treatment.
AB  - The prediction that abnormalities of circadian clock function in humans would
      manifest principally as sleep/wake disruption led to the description of the first
      circadian sleep/wake disorders almost 20 years ago. Since then, formal
      classification of sleep pathology has expanded this category to include six
      specific disorders. In this review, the physiology of mammalian circadian clocks
      is summarized with emphasis on the role of light and hormonal signals in
      circadian adjustment and entrainment. Each of the circadian sleep disorders-time
      zone change (jet lag) syndrome, shift work sleep disorder, irregular sleep/wake
      pattern, delayed sleep phase syndrome, advanced sleep phase syndrome, and non-24
      h sleep wake disorder-is reviewed. Presenting characteristics, approaches to
      diagnosis, models of pathophysiology, and methods of treatment are summarized for
      each sleep disorder. Developments in the understanding of circadian physiology
      offer promise for important advances in the diagnosis and treatment of these
      sleep disorders.

PMID- 8988284
TI  - Circadian rhythm, sleep, and epilepsy.
AB  - This review article: (1) describes the circadian distribution of ictal and
      interictal events; (2) differentiates transitional arousal, non-rapid eye
      movement and rapid eye movement sleep components and their substrates; (3)
      suggests the means by which the neural generators of these seizure-prone vs.
      seizure-resistant sleep and arousal states modulate the timing of different
      seizure manifestations; (4) considers clinical and mechanistic findings for the
      reciprocal effects of seizures and antiepileptic drugs upon the sleep-wake cycle;
      and (5) assesses clinical and basic mechanisms of sleep deprivation effects upon
      seizures.

PMID- 8988285
TI  - Monitoring of median nerve somatosensory evoked potentials during cervical spinal
      cord decompression.
AB  - We evaluated the intraoperative utility of monitoring median nerve somatosensory
      evoked potentials (SEPs) in 31 consecutively hospitalized neurosurgical patients
      (mean age 55.3 +/- 2.1 years) who underwent spinal cord decompression for
      cervical herniated disc, spondylosis, or tumor. Pre- and postoperative standard
      neurological examinations included evaluation of motor function, sensory
      responses, gait, tone, and reflexes. Evoked potentials were recorded from
      clavicular Erb's (N9) and contralateral cortical (N20) points. Intraoperatively,
      SEP measurements were obtained after the onset of anesthesia (baseline control)
      and were repeated throughout the operative procedures. N20 and N9-N20 conduction
      latencies were measured for each SEP recording; disappearance of the SEP waveform
      was interpreted as a nonquantifiable increase in latency. Follow-up neurological
      examinations were made immediately after and up to 6 months following surgery.
      Postoperatively, the 31 study subjects were assigned to one of two groups based
      on neurological evaluation: 27 group I subjects had either no change or
      improvement (good outcome) whereas four group II subjects had postoperative
      neurological deterioration (poor outcome). Intraoperative N9-N20 interpeak
      latency was found to increase during cervical decompression in six of 27 group I
      and in two of four group II subjects. Only two of the Group I subjects exhibited
      increases > 10% (14 and 19%, respectively). Intraoperative communication to the
      surgeon of a marked increase of N9-N20 latency during positioning for cervical
      traction clearly obviated a poor outcome in one group I subject; Upon removal of
      traction, latency decreased and significant changes in neurological function were
      not detected postoperatively. The SEP waveform disappeared in two of the group II
      and in none of the group I subjects. In the two group II subjects exhibiting
      increases of N9-N20 latencies, increments were > 20%. These findings indicate
      that in patients undergoing cervical spinal cord decompression, disappearance of
      SEPs or increases > 20% in the N9-N20 interpeak latency are suggestive of
      operative conditions that place patients at risk for poor neurological outcome.

PMID- 8988286
TI  - Electroencephalographic abnormalities in liver transplant recipients: practical
      considerations and review.
AB  - This article reviews the central nervous system complications of orthotopic liver
      transplantation (OLT) and the contribution of EEG in their assessment. The
      utility of EEG in the evaluation of disturbances of the level of consciousness,
      cerebrovascular disorders, infections, seizures, medication effects, and central
      pontine myelinolysis is discussed. EEG may aid in the assessment of altered
      levels of consciousness, correlate a variety of behavioral manifestations,
      demonstrate the presence of subclinical seizure patterns, and monitor the
      treatment response, thus contributing to the management of the OLT patient.

PMID- 8988288
TI  - Sacral cord conduction time of the soleus H-reflex.
AB  - The sacral cord conduction time of the soleus H-reflex was investigated in 30
      normal adult subjects using three different methods. (1) The posterior tibial
      nerve was stimulated at the popliteal fossa by graded electric shocks, and the
      recordings were made from different lumbar epidural intervertebral levels. The
      afferent action potentials from the dorsal roots and the reflexively evoked
      efferent action potentials from the ventral roots were recorded. The time
      interval between the negative peaks of the ventral and dorsal root potentials was
      used to calculate the approximate sacral cord reflex delay time, which was found
      to be 1.3 ms. on average. (2) The sacral cord reflex delay time was found to be
      about 2.0 ms using the conduction time of the afferent, that of the efferent
      limbs and total reflex time of the soleus H-response. (3) By stimulating the
      lumbosacral roots at the epidural levels and using the difference between the
      soleus H and M response latencies, the sacral cord reflex delay was determined to
      be approximately 2.4 ms. These findings indicated that the soleus H-reflex is
      exclusively monosynaptic. It is proposed that in humans the synaptic transmission
      at the sacral cord is approximately 0.4 ms.

PMID- 8988287
TI  - Repetitive magnetic stimulation of cerebral cortex in normal subjects.
AB  - Changes of excitability in the neuraxis were studied in 11 healthy subjects with
      repetitive transcranial magnetic stimuli of the motor cortex at frequencies of 1
      10 Hz. Following trains of four stimuli, compound muscle action potentials
      (CMAPs) were obtained from the flexor carpi radialis muscle. At an
      interstimulation interval (ISI) of 100-180 ms. the amplitudes of the CMAPs evoked
      by stimuli II and IV were inhibited as compared with the amplitude of the CMAPs
      evoked by the first stimulus. In contrast, the amplitude of the CMAPs evoked by
      stimulus III was almost unchanged. Changes in excitability depended on the
      stimulation intensity. Thus, it was demonstrated that the amplitude of the CMAPs
      evoked by stimulus III was reduced at low stimulation intensities (100 and 110%
      of threshold intensity) but normalized at higher stimulation intensities (120 and
      130% of threshold intensity). Results of H-reflex studies indicated that
      excitability changes at the segmental level are not necessarily involved in the
      inhibition of the CMAPs evoked by stimuli II and IV at an ISI of 100 ms. It is
      proposed that long acting neurotransmitter modulation can explain part of the
      inhibition during repetitive magnetic stimulation, and that recruitment of
      different neurons, due to electric field differences, explains the dependence of
      excitability on stimulation intensity.

PMID- 8988290
TI  - Technology and equipment review. Report generators and databases for
      electromyography.

PMID- 8988289
TI  - Inter- and intraindividual variability of posterior tibial nerve somatosensory
      evoked potentials in comatose patients.
AB  - Thirty-two sequential posterior tibial nerve somatosensory evoked potentials (PTN
      SEP) were recorded in 30 neurologically impaired, ventilated, comatose patients.
      To establish the time invariance of PTN-SEP in this population, Spearman rank
      correlations of latencies, interpeak latency, amplitudes, and mean absolute
      amplitude with time were computed. The results revealed no significant time
      dependency. The mean, standard deviation, and 5th and 95th percentiles for the
      inter- and intraindividual distribution of PTN-SEP parameters, pairwise PTN-SEP
      parameter differences, and direct cross-correlation of PTN-SEP were estimated
      using bootstrap procedures. The standard deviations of the interindividual
      distribution of PTN-SEP parameters are two to three times higher than the
      standard deviations of the intraindividual distributions. The coefficients of
      variation, that is, standard deviations divided by means, for the intraindividual
      distribution of latencies ranged from 0.012 to 0.042, of amplitudes from 0.146 to
      0.230. The mean maximal cross-correlation coefficient of two randomly chosen PTN
      SEP across patients equaled 0.65, and within patients 0.91. These data
      demonstrate the interindividual variability and intraindividual stability of PTN
      SEP. The normal limits of intraindividual variability (1.96 x standard deviation)
      are 3.76, 1.33, 2.92, 6.00, and 3.04 ms for latencies N1, P1, N2, P2, and
      interpeak latency P1-N2, respectively. The intraindividual differences of
      amplitudes N1/P1, P1/N2, N2/P2, and the mean absolute amplitude should not exceed
      0.67, 0.67, 0.90, and 0.27 microV or, expressed as quotients, 61, 52, 41, and
      61%, respectively. The intraindividual maximal cross-correlation coefficient
      should not be lower than 0.74 with a lag of < 2.00 ms. The results of this study
      are of use for discrete and continuous PTN-SEP monitoring on intensive care units
      and during neuroradiological interventions and neurosurgery.

PMID- 8988291
TI  - Current management of the undescended testis.
AB  - True undescended testes are unilateral in approximately 80% of cases, are rarely
      corrected by human chorionic gonadotropin (hCG), and should be treated by
      orchiopexy before the patient reaches the age of 3 years to permit optimal
      tubular development and sperm function. A cryptorchid testis does not mature
      normally after the age of 2 years and may produce adverse effects on the
      contralateral descended testis. The higher a cryptorchid testis resides above the
      scrotum, the more dysgenetic the morphology is likely to be. Hypoplastic
      cryptorchid testes should be removed early, and high-positioned testes that have
      not been surgically placed into the scrotum before midadolescence generally
      should be removed.

PMID- 8988292
TI  - Urinary reconstruction (rather than diversion) for continence in difficult
      pediatric urologic disorders.
AB  - Surgical reconstruction of the pediatric urinary tract for purposes of
      restoration of function is a complex and highly successful undertaking that holds
      the potential of dramatically enhancing a child's health and quality of life.
      Unfortunately, such reconstruction may carry with it adverse sequelae that may
      complicate subsequent therapy and may be difficult to reverse completely. Urinary
      tract function has several components, each of which are essential to ensure
      maximal renal preservation, freedom from clinically significant infection, and
      continence. Several surgical alternatives exist for each component.
      Representative alternatives and surgical judgment with respect to their
      application are reviewed.

PMID- 8988293
TI  - Laparoscopy in pediatric urology: challenge and opportunity.
AB  - The development of operative laparoscopic techniques in Pediatric Urology has
      been generally cautious. It is premature to attempt an assessment of the ultimate
      impact of laparoscopy in pediatric urology, yet several areas of application have
      significant potential. Diagnostic laparoscopy for cryptorchidism has evolved into
      operative laparoscopy for intra-abdominal testes, and a significant number of
      cases have been performed successfully, with the possibility of improved results
      over open techniques. Laparoscopic nephrectomy and nephroureterectomy have been
      spring-boards for complex reconstructive renal surgery, although it is clear that
      new tissue joining technologies are needed. Complex reconstructive surgery is
      just beginning, yet may have a role in practice. These developments and the
      current status of laparoscopy in pediatric urology will be reviewed.

PMID- 8988294
TI  - Laparoscopy in pediatric urology: too much of a good thing?
AB  - Laparoscopy is still an evolving technique; its rightful place in pediatric
      urology has yet to be defined. Although both the first reported use of diagnostic
      laparoscopy in pediatric surgery and its initial use in pediatric urology were
      published in 1973, the field lay dormant until recently. Once operative
      laparoscopy was initiated with the report of laparoscopic cholecystectomy in
      1987, a torrent of articles followed; many operative procedures in adult urology
      and subsequently in pediatric urology appeared. This article presents the
      advantages and the disadvantages of several of the more important and common
      possible indications for laparoscopy in pediatric urology.

PMID- 8988295
TI  - Evaluation of the infant who has ambiguous genitalia, and principles of operative
      management.
AB  - Infants and children with ambiguous genitalia pose challenging diagnostic and
      therapeutic issues for the clinician. Success depends on rapid and precise
      diagnosis, appropriate gender assignment, proper medical therapy, and meticulous
      surgical technique. A well-trained multispecialty clinical team is essential. The
      major disease categories include chromosomal abnormalities, excessive androgen
      syndromes, and deficient androgen syndromes. The specific diseases involved are
      described in this article, as well as the diagnostic and therapeutic
      considerations for each.

PMID- 8988296
TI  - Principles in repair of hypospadias.
AB  - Hypospadias, a common congenital deformity, is the result of incomplete formation
      of the urethra during the 10th- to 14th weeks of gestational life. Surgery to
      repair the foreshortened urethra and penile curvature in hypospadias has a
      history of more than 150 years. To date, more than 300 surgical procedures with
      accompanying variations have been proposed for the repair of hypospadias. With
      modern techniques of tissue transfer, even the most severe case of hypospadias is
      amenable to repair. The modern era of hypospadias surgery has allowed the
      application of skin grafts and flap techniques to add significantly to urethral
      length. At the same time, a variety of new techniques have been proposed to
      "minimize" hypospadias surgery. In this article the authors argue that for the
      worst cases of hypospadias, complete dissection of the abnormal anatomy and
      modern tissue transfer techniques should be used to reconstruct the deformity.

PMID- 8988297
TI  - Genitourinary tract cancer in childhood.
AB  - Tumors of the genitourinary tract are heterogeneous and can be organized
      according to both site and specific histopathology. This article divides these
      neoplasms into primary tumor originating from the kidney, adrenal gland,
      collecting system, urinary bladder, and gonads. Primary renal tumors are further
      subdivided into Wilms' tumors and rare kidney tumors of childhood including clear
      cell sarcoma, rhabdoid tumors, mesoblastic nephromas, and renal cell carcinoma,
      sarcomas, and lymphomas. The rarity and smooth muscle origin of collecting system
      tumors is noted. Adrenal tumors are divided into cortical and medullary. Cortical
      neoplasms include adenomas and renal cortical carcinomas; pheochromocytoma and
      neuroblastoma arise from the adrenal medulla. Bladder and prostate
      rhabdomyosarcomas most frequently affect these organs and are discussed together.
      Finally, gonadal neoplasms with emphasis on germ cell tumors of these organs are
      presented. The multidisciplinary approach and importance of the pediatric
      surgical oncologist in the management of genitourinary tumors in childhood are
      emphasized.

PMID- 8988298
TI  - Early primary valve ablation for posterior urethral valves.
AB  - Early diagnosis and the use of new pediatric endoscopic equipment have
      significantly improved the survival of infant boys with posterior urethral
      valves. The sequelae of urethral obstruction in these patients includes
      abnormalities in the urethra, bladder, ureters, and kidneys. The question remains
      of how best to treat all valve patients to maximize function of the entire
      urinary tract. Our experience with early valve ablation (EVA) suggests that the
      damaged bladder and upper tracts have a potential to heal if the obstruction is
      removed and the bladder is allowed to fill and empty cyclically in the first few
      months of life. One year after EVA, even patients with severe obstructive changes
      show return of normal bladder capacity and compliance, and resolution or
      improvement in reflux. Unfortunately, the renal insufficiency associated with
      valves often is secondary to primary renal dysplasia, with many patients
      progressing to renal failure and transplantation. Upper tract diversion has
      failed to improve long-term outcome in patients with renal dysplasia;
      furthermore, it jeopardizes the potential for bladder healing and normal bladder
      function. Therefore, even for patients with renal insufficiency, early primary
      ablation should be used as the definitive treatment for posterior urethral
      valves.

PMID- 8988299
TI  - Urogenital sinus and cloacal malformations.
AB  - Urogenital sinus and cloacal malformations comprise a wide spectrum of abnormal
      anatomy. This article discusses lessons learned from treating these anomalies for
      4 decades. Once the outlook was dim for these children. Today there is a good
      surgical solution for most of their problems.

PMID- 8988300
TI  - Academic health centers in an era of managed care.

PMID- 8988301
TI  - The impact of managed care on practicing physicians.

PMID- 8988302
TI  - Medicaid managed care: state experiences.

PMID- 8988303
TI  - Image and reality: managed-care experiences by type of plan.

PMID- 8988304
TI  - Questions from the floor. Commonwealth fund investigations of managed care.

PMID- 8988305
TI  - Keynote address. Danger and opportunity: the new economics of health care.

PMID- 8988306
TI  - Presentation of the Margaret E. Mahoney Award.

PMID- 8988307
TI  - Characterization of Trichuris skrjabini by isoenzyme gel electrophoresis:
      comparative study with Trichuris ovis.
AB  - Morphological and biometric studies were performed in Trichuris skrjabini
      (Baskakov, 1924) collected from the caecum of Capra hircus. The LDH (EC
      1.1.1.27.), G6PD (EC 1.1.1.49.), GPI (EC 5.3.1.9.), MDH (EC 1.1.1.37) and malic
      enzyme (ME) (EC 1.1.1.40) isoenzymatic patterns of T. skrjabini were determined
      by starch gel electrophoresis. The G6PD and GPI isoenzymatic patterns of T.
      skrjabini displayed two anodic bands for both enzymes: one fast migration band
      and one band near the origin. This isoenzymatic pattern was interpreted as two
      gene loci encoding both enzymes. The LDH isoenzymatic pattern of T. skrjabini was
      characterized by the presence of a cathodically migrating band, while the MDH
      isoenzymatic pattern showed a very slow cathodic band. These two phenotypes were
      interpreted as the expression of a homozygous state of a gene locus for LDH and
      MDH in T. skrjabini. The ME isoenzymatic pattern was characterized by the
      presence of a single anodic band. Further, comparative isoenzymatic studies were
      carried out between T. skrjabini and T. ovis. The different G6PD, GPI, LDH, MDH
      and ME isoenzymatic patterns observed for both species allowed us to distinguish
      them and therefore to use isoenzymatic patterns as a diagnostic tool to
      differentiate species of Trichuris.

PMID- 8988308
TI  - A comparative study of the parasitological buffy coat technique and an antigen
      enzyme immunoassay for trypanosome diagnosis in sequential Trypanosoma congolense
      infections in N'Dama, Gobra zebu and N'Dama x Gobra crossbred cattle.
AB  - The buffy coat/dark ground techniques (BCT) and an antigen enzyme immunoassay (Ag
      ELISA) were compared for the diagnosis of trypanosome infection in N'Dama, Gobra
      zebu and N'Dama x Gobra (F1) crossbred cattle following two sequential
      experimental Trypanosoma congolense infections. Both first and second challenge
      were performed by intradermal needle inoculation of trypanosome bloodstream
      forms. During the course of the first challenge, the overall trypanosome
      percentage of positive cases detected by BCT in blood samples was higher (P <
      0.001) in comparison with that obtained by Ag-ELISA in tested serum samples of
      the three cattle breeds. Conversely, in the second infection the overall number
      of infections detected by BCT was lower in N'Dama (P < 0.005) and F1 (P < 0.001)
      than that obtained using Ag-ELISA; nearly identical positive rates were detected
      by the two diagnostic techniques in Gobra zebus. Both in the first and second T.
      congolense challenge, positive rate obtained using BCT significantly decreased as
      the infection progressed. On the other hand, the positive rate given by Ag-ELISA
      and its sensitivity manifested a significant opposite trend during the course of
      the first infection. No relationship between progression of infection and Ag
      ELISA positive rate as well as Ag-ELISA sensitivity was found in the second T.
      congolense challenge. The Ag-ELISA was less than 50% sensitive in detecting
      circulating antigens during the first 2 months of the primary infection. However,
      it showed a high and stable sensitivity throughout the second trypanosome
      infection. It was concluded that the Ag-ELISA was suitable for use in detecting
      chronic or repeated infections but needs to be combined with BCT to provide
      reliable results.

PMID- 8988309
TI  - The importance of 2,3-dimercaptopropinol (British anti-lewisite, BAL) in the
      trypanocidal activity of topical melarsoprol.
AB  - Both melarsomine dichlorhydrate (mel Cy, Cymelarsan) and melarsen oxide can be
      dissolved in dimethylsulfoxide and converted into a gel by the addition of
      hydroxypropylcellulose. When Trypanosoma brucei brucei-infected mice are treated
      topically with these gels the circulating trypanosomes are rapidly cleared from
      the circulation but the infections relapse soon after the last application.
      However, when these two compounds are allowed to react with 2,3
      dimercaptopropinol (British anti-lewisite, BAL) and form "melarsoprol" their
      efficacy, especially in the case of mel Cy, is restored to that of commercial
      melarsoprol (Arsobal) and trypanosomes in the central nervous system (CNS) can be
      eliminated. This would indicate that the dimercaptopropinol portion of the
      molecule does not act solely as an "antidote" to arsenic toxicity, but also plays
      an important role in the absorption of melarsoprol through the skin and/or blood
      brain barrier into the CNS and/or into the trypanosome.

PMID- 8988310
TI  - Extraction of Schistosoma haematobium antigens from infected human urine and
      generation of potential diagnostic monoclonal antibodies to urinary antigens.
AB  - Proteins in Schistosoma haematobium infected human urine were concentrated by
      precipitation with saturated ammonium sulphate 50% (v/v) and various fractions
      obtained at different stages of precipitation tested for presence of schistosome
      antigens (ShAgs) by dot-ELISA. The protein fraction (UP2S) obtained following two
      times precipitation was found to contain high concentrations of ShAg. Fraction
      UP2S was dialysed against phosphate-buffered saline (pH 7.4) and further purified
      by Sephadex G-200 column chromatography. Two protein peaks were eluted of which
      the first peak UP2S(pkI) was found to contain high concentrations of ShAgs as
      determined by microplate-ELISA. The second peak UP2S(pkII) consisted of human
      urine proteins. Further analysis of UP2S(pkI) revealed that ShAgs were mainly in
      the form of immune complexes with human IgG, IgM, IgA, IgE and complement C3. The
      ShAgs in both UP2S and UP2S(pkI) were found to be active as they induced immune
      responses in mice which produced antibodies reactive with S. haematobium worm as
      well as soluble egg antigens (SEA). Pure ShAgs were obtained from UP2S following
      dissociation of immune complexes with a carbonate buffer (pH 11.42) and further
      purification on Sephadex G-200. Immunizations with UP2S led to the generation of
      MoAbs which could bind both SEA and UP2S.

PMID- 8988311
TI  - Dynamic aspects of morbidity and acquired immunity in schistosomiasis control.
AB  - In schistosomiasis control, rational planning of chemotherapy programmes is
      complicated by the dynamic interactions between treatment and levels of acquired
      immunity and morbidity in the community. In this paper, mathematical models that
      address the development of acquired immunity and the prevalence of morbidity are
      incorporated within an age-structured transmission framework to explore some of
      the dynamic complexities of long-term chemotherapy programmes. As well as
      illustrating some of the potential problems inherent in predicting the
      consequences of control measures, the model provides insights into the dynamics
      of schistosomiasis transmission and the parameters that need to be measured to
      further improve the design of community-based control programmes.

PMID- 8988312
TI  - Oxidation of nutrients in bull calves treated with beta-adrenergic agonists.
AB  - Oxidation of protein (OXP), carbohydrate (OXCHO) and fat (OXF) was investigated
      with 12 growing bulls treated with beta-agonist (L-644, 969) during two 6 weeks
      trials (Section A and B) at a mean live weight of 195 and 335 kg. Heat production
      and nutrient oxidation was calculated from gas exchange, with CO2 reduced for CO2
      from fermentation processes, and nitrogen excretion in urine. The beta-agonist
      had no effect on the level of rumen fermentation as indicated by the same methane
      production for control and treated animals. Heat Production (HE, RQx) increased
      by the treatment of beta-agonist corresponding to the increment in the protein
      retention. OXP/HE,RQx was reduced to about 10% in treated animals, indicating
      that in order to supply amino acids for an increased protein deposition oxidation
      of protein is decreased. OXF/HE,RQx were markedly higher in treated animals, but
      as indicated by the same CH4 production the level of the short chain fatty acids
      (SCFA) production was the same. Therefore, it was concluded that the increase in
      OXF was not caused by an increase in SCFA but by a direct influence of beta
      agonist on mobilization and oxidation of body fat.

PMID- 8988313
TI  - The pattern of protein and energy retention and the chemical composition of the
      body in White Leghorn pullets.
AB  - The change of body composition, energy content and energy and protein balance was
      studied in White Leghorn pullets from hatching to 140 days of age. The animals
      received corn, soybean meal and fish meal based diets ensuring maximal growth.
      Correlations were established between ingested feed and body weight gain both
      from the point of view of quantity and quality, determining the content of
      protein, fat, ash, water and energy in the total body and in feathers,
      separately. On the basis of digestibility and comparative slaughtering the energy
      and protein requirements for maintenance and for protein and fat retention were
      calculated. The obtained results can be utilised to develop a mathematical model
      for energy and protein retention in growing White Leghorn pullets.

PMID- 8988314
TI  - Effect of microbial phytase on cadmium accumulation in pigs.
AB  - 2 x 6 pigs continuously housed in metabolic cages from 25-100 kg weight were fed
      N-reduced diets based on barley, maize and soybean meal. Diet I (control)
      contained in FM (fresh matter) 0.56%, 0.48% and 0.46% P (feeding phases A: 25-50
      kg, B: 50-75 kg, C: 75-100 kg weight) and 0.76%, 0.71% and 0.68% Ca. Diet II was
      low in P (0.46%, 0.40%, 0.32%) and Ca (0.69%, 0.62%, 0.52%) and 800 U Aspergillus
      phytase per kg were added. Analyzed cadmium concentrations in diet I were 23.4,
      19.9 and 13.7 micrograms/kg FM and 20.6, 14.9 and 12.7 micrograms/kg FM in diet
      II respectively. At 100 kg weight in both treatment groups low cadmium
      concentrations in liver (11.8 vs. 17.3 micrograms Cd/kg FM) and kidneys (59.6 vs.
      102 micrograms Cd/kg FM) were found. Contrary to findings for rats fed
      semisynthetic diets enriched with high CdCl2 levels, phytase supplementation to
      the P- and Ca-reduced pig diet with a low Cd concentration significantly enhanced
      liver and kidney cadmium accumulation. Differences in dietary Cd levels, the
      binding form of Cd in the diets and the duration of the experimental trials may
      partially explain the differences found between rats and pigs. Complex
      interactions between cadmium and various elements, especially calcium, might also
      have additionally influenced the carry over of cadmium in the present study.
      Irrespective of the dietary treatment, liver and kidney cadmium concentrations in
      both groups were considerably lower than maximal permitted values.

PMID- 8988315
TI  - Comparison of the influence of dietary fibre sources with different proportions
      of soluble and insoluble fibre on Ca, Mg, Fe, Zn, Mn and Cu apparent absorption
      in rats.
AB  - The 6 week experiment was performed on growing Wistar male rats. In the third and
      the sixth weeks digestibility trials were performed. The following high fibre
      preparations were supplemented to the control diet (C): high methoxylated citrus
      pectin (Cr); apple pomace (A), potato fiber "Povex" (P) and sugar beet pulp (B).
      Fibre supplementation, except Cr, significantly increased Ca, Mg, Fe, Mn, Zn, Cu
      excretion in faeces and decreased their apparent absorption in both trials.
      Significant correlations (P < or = 0.001) were found between crude, insoluble and
      total fibre intake and mineral excretion and apparent absorption. Apparent
      absorption of minerals increased from the third to the sixth week in group C and
      in group Cr, except Fe, while it decreased in groups P and B or showed tendency
      to decrease. In the sixth week the following differences (P < or = 0.05) in
      apparent absorption were observed between diets, in descending order: [equation:
      see text]

PMID- 8988316
TI  - Effect of feeding various dietary vitamin B6 concentrations during gestation and
      lactation on vitamin B6 level in liver and carcass of rat dams.
AB  - The present investigation was designed to determine the vitamin B6 concentration
      in liver and carcass of rat dams fed various dietary vitamin B6 levels during
      gestation and lactation. Therefore, gravid female rats received 0.6, 3, 6, 18 or
      180 mg vitamin B6 per kg diet. After parturition each group was divided into 2
      groups of 8 dams each, which received then a diet with 3, respectively 6 mg/kg
      vitamin B6 during lactation. At the end of the experiment at day 14 of lactation
      weight gain and food consumption as well as liver and carcass weights did not
      differ within the groups. The present data clearly show that both in liver and
      carcass of lactating rats, there exists only a slight dose-response-relationship
      between the dietary vitamin B6 intake and the vitamin B6 concentration in body
      tissue. Moreover, liver reflects the various vitamin B6 supplies during gestation
      and lactation somewhat better than carcass. The distribution of the vitamins did
      not differ among the groups and was therefore independent of the vitamin B6
      supply. The present findings, especially regarding the liver, elucidate, that an
      adequate vitamin B6 supply during lactation can not compensate for a lack of
      vitamin B6 during gestation and vice versa a high dose of vitamin B6 during
      gestation did not completely protect against a suboptimal vitamin B6 during
      lactation.

PMID- 8988317
TI  - Crude protein degradability, protein digestible in the intestine and net energy
      for lactation of whole crop barley in various vegetative stages.
AB  - Crude protein degradability (CP deg), protein digestible in the intestine (PDI)
      and net energy of lactation (NEL) content of whole crop spring barley were
      estimated by means of the in situ method using three steers fitted with rumen
      cannulas and fed near the maintenance level of nutrition. Barley was cut in five
      consecutive vegetative stages (end of the earing, S1, end of the flowering, S2,
      middle of the milky stage of the grain, S3, beginning of the dough stage, S4,
      middle of the dough stage, S5, including S5 silage). CP deg, PDI and NEL were
      significantly (P < 0.01) affected by the growth stage. The relationships of the
      CP deg (%), PDI (g/kg DM) and NEL (MJ/kg DM) to the vegetative stage of barley
      quantified on a decimal scale (X) were as follows: CP deg = 40.1 + 0.46X (I2yx =
      82%), PDI = -330.8 + 12.86X-0.1007 X2 (I2yx = 83%), and NEL = -0.48 + 0.0802X
      (I2yx = 86%), resp. Compared with drying at 60 degrees C ensiling increased CP
      deg (P < 0.01) and NEL (P < 0.05), whereas PDI was not affected (P > 0.05).

PMID- 8988318
TI  - Attempts to induce reductive acetogenesis into a sheep rumen.
AB  - A rumen fistulated wether was used for continuous infusion of a 2
      bromoethanesulfonic acid (BES) solution (2 g/d in 50 ml of water). The infusion
      was started after introduction of a pulse dose of BES (2 g) into the rumen.
      Immediately after introduction of the pulse dose, methane concentration in rumen
      gases was lowered from about 40 to less than 1%, with concomittant decreases and
      increases in the molar proportions of acetic and propionic acids respectively in
      the rumen volatile fatty acids. After 4 days of infusion however, and despite
      repeated pulse dosage of BES, methanogenesis adapted to BES and methane
      concentration in rumen gases reached 20%. Addition of BES to incubations of rumen
      contents with hay resulted in considerable inhibition of methanogenesis. Extra
      addition of methanol in such incubations increased both acetate and methane
      production, whereas addition of formate had no effect. In a second experiment
      using a second rumen fistulated whether, a 4 day control period was followed by
      10 days of daily introduction of 11 of cattle cecal contents into the rumen. The
      cattle cecal contents were collected from slaughterhouse cattle, filtered and
      kept at -20 degrees C until use. Comparison of in vitro fermentation of thawed
      with fresh contents showed absence of methanogenesis but not of reductive
      acetogenesis after freezing and thawing. Evidence for the latter was sought by
      calculation of metabolic hydrogen recoveries from amounts of end products formed
      in incubations. In a similar way, evidence for induction of reductive
      acetogenesis was sought from incubations in vitro, carried out with rumen
      contents obtained before, during and after introduction of cecal contents into
      the rumen. No such evidence was obtained.

PMID- 8988319
TI  - Epitope mapping of preS2 of the hepatitis B virus surface antigen against a
      conformation-dependent monoclonal antibody using synthetic peptides.
AB  - Previously we reported that the N-terminal sequence 120/123-129 of the preS2
      region of the hepatitis B virus surface antigen plays an important role on
      peptide antigenicity against a monoclonal antibody H8 (H8 mAb) by affecting the B
      cell epitope conformation of a peptide existing within the sequence 130-145 (Lee
      et al., Biochem. Mol. Biol. Int., 34, 159-168, 1994). In this study, we try to
      map the H8 mAb binding site using a series of substituted peptides in the
      sequence 131-143 by competitive ELISA. Peptide antigenicities were greatly
      reduced when the residues 131 (L), 137 (R), 140 (Y), 141 (F) and 142 (P) were
      substituted. The residues 133 (D), 134 (P) and 136 (V) had a slight affect on the
      mAb binding, whereas the residues 135 (R) and 139 (L) had no effects on the mAb
      binding. In contrast to H8 mAb, however, three anti-HBsAg polyclonal antisera
      showed the lowest bindings to the peptide substituted at position 135. These
      results suggest that the epitope against H8 mAb is discontinuously
      conformational.

PMID- 8988320
TI  - Modulation of ouabain sensitive sodium potassium pump of erythrocytes from
      patients with chronic renal failure: role of acute hemodialysis.
AB  - Significantly higher levels of plasma urea creatinine and potassium were observed
      in patients with renal failure compared to normal controls. The RBC sodium
      concentration was raised whereas the RBC potassium concentration was decreased in
      chronic renal failure. These alterations in the RBC Na+ and K+ concentrations
      were associated with decrease in ouabain sensitive sodium efflux rate and ouabain
      sensitive sodium efflux rate constant. However, there was no significant impact
      of acute hemodialysis on the intracellular electrolytes levels, ouabain sensitive
      sodium efflux rate and ouabain sensitive sodium efflux rate constant. These
      findings suggest an intrinsic alteration in the transport capacity of Na(+)-K+
      pump which could account for the rise in intracellular sodium and fall in
      intracellular potassium content in the RBCs of chronic renal failure patients.

PMID- 8988321
TI  - Activation of grass carp liver alcohol dehydrogenase by limited proteolysis.
AB  - Limited proteolysis of grass carp alcohol dehydrogenase by alkaline protease or
      subtilisin BPN' at 30 degrees C for 6 hr generated a nicked species that was
      catalytically active. Electrophoresis on a denaturing SDS-PAGE showed that the 40
      kDa subunit of the intact enzyme was cleaved to produce subunits of 27 and 13
      kDa, which remained tightly associated with each other under native condition.
      Such a proteolytically nicked form was catalytically more active than the
      original intact form of the enzyme. The Vmax value toward the oxidation of
      ethanol at pH 10 increased by 7.8 fold whereas the K(m) value also exhibited a
      140 fold increase. On the other hand, when the same protease treatment was
      applied to horse liver alcohol dehydrogenase, no activation nor any specific
      cleavage can be observed.

PMID- 8988322
TI  - Pattern recognition approach to nucleic acid sequences.
AB  - A pattern recognition method through the two dimensional matrix representation of
      the nucleic acids sequence is developed. This approach of two dimensional
      plotting primarily enables to visualize all types of bonding between different
      bases in a RNA or DNA. The two dimensional matrix uses the capability of
      intramolecular Watson-Crick type (A-U and C-G) and Wobble type (G-U) base
      pairing. The method discusses both parallel and anti-parallel stranded base
      pairing. The application of the method to tRNA is shown.

PMID- 8988323
TI  - Antioxidant property of Fructus Momordicae extract.
AB  - The antioxidant effect of Fructus Momordicae extract, FME (mogrosides 75
      approximately 80%), was studied. FME reduced the stable free radical 1,1-diphenyl
      2-picrylhydrazyl (DPPH) and scavenged superoxide radicals (O2-) generated by a
      hypoxanthine and xanthine oxidase system. It also scavenged hydroxyl radicals
      (.OH) generated by Fenton reaction. In addition, FME inhibited Fe(II) induced
      lipid peroxidation in rat cortex homogenates in a dose-dependent manner, as
      indicated by decreased thiobarbituric acid-reactive substances (TBARS) formation.
      Oral administration of FME inhibited TBARS and malonaldehyde (MDA) formation in
      the ipsilateral cortex 30 min after iron-salt injection into the left cortex of
      rat. FME showed inhibitory effect on 4-hydroxy-2(E)-nonenal (4-HNE) formation
      induced by Fe(III) injection into the rat cortex. These data suggest that Fructus
      Momordicae extract has an antioxidant activity against free radicals and lipid
      peroxidation.

PMID- 8988324
TI  - The role of chelators in the catalysis of glutathione-gamma-glutamyl
      transpeptidase-dependent lipid peroxidation by transition metals.
AB  - A gamma-glutamyl transpeptidase-glutathione (GGT-GSH) system induces transition
      metal-dependent lipid peroxidation (LPO). The role of the transition metals iron
      and copper in this system was studied by determination of LPO rates, the rates of
      Fe3+ reduction, and the steady state concentration of Fe2+ as function of
      concentration of o-phenanthroline or citrate. Optimum curves were obtained,
      compatible with the idea that Fe2+ chelated by an entity other than o
      phenanthroline or citrate is important in thiol-driven LPO. Cu enhanced LPO at
      low concentrations, inhibited LPO at high ones, and catalytically elevated the
      steady state concentration of Fe2+. Relating the steady states of Fe2+ at various
      chelator concentrations with those of LPO rates, indicate that a Fe(2+)-O-O-Fe3+
      complex may not be the principal oxidizing entity. The above, and the resistance
      of LPO to catalase, superoxide dismutase and mannitol are compatible with the
      notion that the Fe which participates in redox cycles is chelated to an entity
      that may be refractory to the action of these antioxidants.

PMID- 8988325
TI  - A new simple method of representing relative orientation of bases in DNA helical
      structures.
AB  - It is shown that the strandwise correlation of the torsion angles in Nucleic acid
      structures can throw light on the aspects like helical distortion, in double
      helical and other associated forms. The single crystal X-ray coordinates for 7 A
      DNA, 29 B-DNA, 8 Z-DNA and 4 tRNA structures are used to calculate the glycosyl
      angle chi and they are plotted in a two dimensional plot. A new torsion angle pi
      is defined as O4'-C1'-N1(9)-X, where X is a fictitious atom on the normal at
      N1(9). The chi 1 vs. chi 2 plots (where 1 and 2 refer to I and II-strand of DNA
      respectively) show the characteristic clustering features of A, B and Z DNAs.
      They are also compactly reflected in the modified graphical representation like
      (chi 1 + chi 2) vs. magnitude of chi 1 - chi 2 plot. chi 1 vs. chi 2 plot of the
      Hoogsteen type of base pairing obtained from the tRNA structures is off diagonal.
      The distortions due to complexing of the structures under each category, in
      particular, B-DNAs is readily observed. The observed points of A/B hybrid form
      clusters between A and B uncomplexed forms. The new torsion angle pi shows
      similar behavior as that of chi.

PMID- 8988326
TI  - Effects of metabolic inhibitors and lectins on the menadione-dependent generation
      of H2O2 by rat thymocytes.
AB  - The capacity of oxidative metabolism and its regulation is an important factor in
      disease control. Using scopoletin as a fluorescent substrate of peroxidase the
      extent of menadione-dependent production of H2O2 by rat thymocytes was
      determined. The reaction was inhibited by 2,4-dinitrophenol, papaverine,
      nordihydroguaiaretic acid and iodacetamide. The membrane-penetrating SH reagent N
      ethylmaleimide primed the reaction, probably due to an inhibition of glutathione
      peroxidase. To delineate an influence of cell-surface protein-carbohydrate
      interactions by exogenous lectins, the impact of cell binding was analyzed for
      several plant lectins, namely concanavalin A, phytohemagglutinin, the lectins
      from Triticum vulgaris and from Sambucus nigra. Except for the alpha-NeuNAc(2
      6)gal/galNAc-binding agglutinin, the other three plant proteins with
      specificities to different parts of N-linked oligosaccharides primed the
      reaction. This activity of lectins did not coincide with their ability to
      aggregate cells. The given results indicate that biosignaling pathways triggered
      by lectins are involved in the regulation of the intracellular reduction of
      menadione.

PMID- 8988327
TI  - Properties of the regulatory subunit of cAMP-dependent protein kinase type II
      from human brain.
AB  - The regulatory subunit type II (RII) of cAMP-dependent protein kinase purified
      from human brain was represented by two proteins with apparent molecular masses
      of 51-52 kD and 54 kD. Dephosphorylation of human RII containing 3 mol
      phosphate/mol protein did not change the electrophoretic pattern. One-dimensional
      peptide mapping of 51-52 kD and 54 kD proteins after digestion with St. aureus V8
      protease evidenced to their being distinct proteins. The data obtained permit to
      assume that human RII of neural type is represented by two isoforms.

PMID- 8988328
TI  - Lipocortin 1 binding sites on human T-cells: the population of cells with the
      binding sites is larger in CD8+ T-lymphocytes than in CD4+ T-lymphocytes.
AB  - Lipocortin 1 (LC1) is believed to be a mediator of glucocorticoids in displaying
      anti-inflammatory and immune suppressive responses. The existence of specific LC1
      binding sites (putative receptor) on monocytes and neutrophils has been reported.
      We have studied the distribution of LC1 binding sites in human peripheral blood
      leukocytes by flow cytometry. The population of cells with LC1 binding sites was
      much larger in monocytes than in lymphocytes in both rheumatoid arthritis
      patients (93.1 +/- 2.3% vs 8.8 +/- 1.0%) and healthy volunteers (97.0 +/- 0.9% vs
      9.9 +/- 1.5%). The LC1 binding cell population was larger in CD8+ T-lymphocytes
      than in CD4+ T-lymphocytes in both healthy volunteers (26.4 +/- 4.5% vs 10.6 +/-
      2.0%) and rheumatoid arthritis patients (28.8 +/- 4.7% vs 8.7 +/- 2.1%). No
      difference in LC1 binding cell populations was found between rheumatoid arthritis
      patients and healthy controls.

PMID- 8988329
TI  - Expression of mRNA encoding cAMP-specific phosphodiesterase isoforms in rat
      parotid glands.
AB  - In previous reports, we have shown that cAMP-specific phosphodiesterase (PDE4) is
      the major PDE in the rat parotid gland, and that PDE4 is activated by
      phosphorylation. In this study, we investigated the expression of PDE4 isoform
      genes and alternative splicing variants of PDE4D in the rat parotid gland using
      reverse transcriptase-polymerase chain reaction (RT-PCR). PDE4A, PDE4B, PDE4C and
      PDE4D of PDE4 subfamily were expressed. PDE4D was found to be the dominant PDE4
      isoform. A weak band of PDE4C was detectable. Three alternative splicing variants
      (PDE4D1, PDE4D2 and PDE4D3) derived from the rat PDE4D gene were expressed in the
      parotid gland. These data suggested that the intracellular cAMP level is
      regulated by multiple response mechanisms through the activations of the PDE by
      phosphorylation and gene expression in the rat parotid gland.

PMID- 8988330
TI  - Magnesium depletion impairs myocardial carbohydrate and lipid metabolism and
      cardiac bioenergetics and raises myocardial calcium content in-vivo: relationship
      to etiology of cardiac diseases.
AB  - This study examines the effects of Mg depletion on myocardial bioenergetic,
      carbohydrate, lipid and phospholipid metabolism. Rats were studied after long
      term (12 week) selective dietary restriction of Mg (20% normal dietary intake).
      Myocardial biopsy samples were examined for glucose 6-phosphate and glycogen to
      evaluate carbohydrate pathways and for glycerol phosphate and mitochondrial fatty
      acid oxidation and phospholipid contents to evaluate lipid and phospholipid
      turnover. Dietary Mg deficiency resulted in falls in myocardial glycogen, glucose
      6-phosphate, glycerol phosphate, as well as the contents of phosphatidylcholine
      (PC), phosphatidylethanolamine (PE), diphosphatidyl glycerol (DPG), phosphatidyl
      inositol (PI) and total phospholipid phosphorus. These observations demonstrate
      impaired phospholipid metabolism, probably at the biosynthetic level. The
      mitochondrial oxidation of long-chain fatty acids was also impaired after Mg
      depletion. Mg depletion (serum Mg fell 60%) also resulted in significant falls in
      myocardial [ATP], phosphocreatine (PCr), and Mg with a concomitant rise in
      myocardial Ca content. These observations are consistent with the tenet that
      prolonged low [Mg2+]zero can result in marked reduction in oxygen and substrate
      delivery to the cardiac myocytes, with concomitant changes in membrane
      phospholipids (potentially resulting in a pro-oxidant state) probably as a result
      of coronary vasoconstriction.

PMID- 8988331
TI  - Phosphatidylserine directs differential phosphorylation of actin and
      glyceraldehyde-3-phosphate dehydrogenase by protein kinase C: possible
      implications for regulation of actin polymerization.
AB  - The phospholipid-dependent protein kinase C is implicated in the regulation of
      cellular motility and energy metabolism. Phosphatidylserine, a main cofactor of
      protein kinase C, is involved in the regulation of glyceraldhehyde-3-phosphate
      dehydrogenase, which as actin, was shown to be phosphorylated by purified protein
      kinase C. Here, we study the effect of phosphatidylserine on the enzyme-substrate
      interaction of protein kinase C with glyceraldhehyde-3-phosphate dehydrogenase
      and actin. The stoichiometry of glyceraldhehyde-3-phosphate dehydrogenase
      phosphorylation is not affected by varying the level of phosphatidylserine.
      However, actin phosphorylation is dependent on phosphatidylserine level, peaking
      at high phosphatidylserine concentration. Moreover, if actin and glyceraldhehyde
      3-phosphate dehydrogenase are cophosphorylated at high phosphatidylserine
      concentration, actin phosphorylation is favored, despite lower affinity for
      protein kinase C. Hence, phosphatidylserine directs differential phosphorylation
      of these key proteins of glycolysis and cellular motility and might be capable of
      recruiting protein kinase C for preferential actin phosphorylation. The
      sedimentation of phosphorylated actin is increased 3.8 fold and total actin 1.7
      fold, suggesting that phosphorylation promotes actin polymerization.

PMID- 8988332
TI  - Proton gradients during salt adaptation of Synechococcus.
AB  - The ability of cells to energize their membranes during salt-adaptation as
      measured by delta pH was studied using the electron spin resonance (ESR) spin
      probe technique. Salt-adaptated cells have the following features: an increased
      stability of delta pH across the cytoplasmic membrane and a significantly lower
      rate of delta pH formation across the thylakoid membrane. Therefore, during salt
      adaptation, the cytoplasmic membrane takes over the role of primary energizing
      membrane from the thylakoid membrane. In contrast to non-adapted cells, delta pH
      across the thylakoid membrane of salt-grown cells is higher under respiratory
      than under photosynthetic conditions.

PMID- 8988333
TI  - Tempace and troxyl-novel synthesized 2,2,6,6-tetramethylpiperidine derivatives as
      antioxidants and radioprotectors.
AB  - Two novel 2,2,6,6-tetramethylpiperidine derivatives (Tempace and Troxyl) were
      synthesized and their capacity to act as scavengers of superoxide, inhibitors of
      iron and ascorbate-driven Fenton reaction and radioprotectors was tested. The
      possibility for one-electron oxidation of novel compounds by heme-ferryl species
      was also examined. The results clearly indicate that Tempace and Troxyl are
      acting as promising antioxidants and radioprotectors thus providing a base for
      further investigations and pharmacological applications.

PMID- 8988334
TI  - Azospirillum lipoferum tRNAs: fractionation and identification of tRNA species
      and the nucleotide sequence of tRNA(Asn) (QUU).
AB  - Transfer RNAs of Azospirillum lipoferum were separated by two-dimensional gel
      electrophoresis and identified by aminoacylation. Thirty-six tRNA spots were
      resolved by this technique and twenty-six tRNA species have been identified.
      There are five tRNAs for Leu, four for Val, three for Pro, two each for Arg, Ile,
      Lys and Tyr, and one each for Ala, Asp, His, Phe, Ser and Thr. The tRNA (Asn)
      (QUU) was purified and its nucleotide sequence was determined. The A. lipoferum
      tRNA (Asn) (QUU) is 92% similar to B. subtilis tRNA (Asn) gene and two
      hypermodified nucleosides, queuosine (Q) and N-(9-beta-D Ribofuranosylpurine-6
      YL)-carbamoyl)-threonine (t6A) are present in this tRNA.

PMID- 8988335
TI  - Structural determinants of cobrotoxin affect its mobility on sodium dodecyl
      sulfate polyacrylamide gel.
AB  - In order to identify the structural determinants of cobrotoxin that caused its
      anomalous mobility in sodium dodecyl sulfate (SDS) gel, comparative studies on
      the capacities of cobrotoxin and its modified derivatives for binding with SDS
      were made. Cobrotoxin migrates faster in SDS gel after modification of Lys
      residues or carboxylated groups. However, the capacities of modified derivatives
      for binding with SDS molecules did not show a positive correlation with their
      electrophoretic mobilities. Moreover, it was found that the segment at positions
      22-38 had the greatest capacity to bind with SDS than other segments of
      cobrotoxin, but guanidination of Lys residues of this peptide fragment did not
      significantly change its migration. These results suggest that the SDS-binding
      capacity of cobrotoxin is not solely responsible for its anomalous mobility in
      SDS gel, and that the effects may arise from the electrostatic interactions
      between Lys residue and carboxylated groups.

PMID- 8988336
TI  - Identification and immunohistochemical localization of macrophage migration
      inhibitory factor in human kidney.
AB  - Macrophage migration inhibitory factor (MIF) was the first lymphokine identified
      in activated T-lymphocytes. MIF can induce proinflammatory cytokines, such as
      interleukin-1 and tumor necrosis factor-alpha. In this study, we identified MIF
      expression in a tissue specimen of a normal portion of a nephrectomized human
      kidney by reverse transcription-polymerase chain reaction (RT-PCR) and Western
      blot analysis. Furthermore, immunohistochemical study using an anti-human MIF
      polyclonal antibody demonstrated that MIF was mostly present in the renal tubule
      epithelial cells and, to a lesser extent, in Bowman's capsular epithelial cells.
      We also carried out immunohistochemistry on cultured human renal proximal tubule
      epithelial cells, which showed that MIF was present in the cytoplasm of the
      epithelial cells. These results suggest the possibility that MIF takes part in
      the mechanism of inflammation and immunological events in the human kidney.

PMID- 8988337
TI  - Effect of cyclic GMP produced by natriuretic peptides on osteoblast-like MC3T3-E1
      cells.
AB  - The C-type natriuretic peptide (10(-7) M) and atrial natriuretic peptide (10(-7)
      M) enhanced cGMP accumulation by 418 and 83 times the control value,
      respectively, in osteoblast-like MC3T3-E1 cells. The natriuretic peptide B
      receptor was assumed to be the major natriuretic peptide receptor. 8
      Bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) activated alkaline
      phosphatase doubled the activity versus the control value on day 15.
      Phosphodiesterase activity was not stimulated by the addition of cGMP (1 MicroM).
      cGMP-dependent protein kinase (G kinase) activity of the supernatant fraction was
      25.5 pmol/min/mg protein. The 42 kDa protein band was detected to be
      phosphorylated by G kinase on SDS-PAGE. These results supported the hypothesis
      that natriuretic peptides regulate the differentiation of MC3T3-E1 cells through
      a cGMP-dependent pathway.

PMID- 8988338
TI  - Interleukin-4 stimulates rheumatoid synovial fibroblasts to express matrix
      metalloproteinase-1 (tissue collagenase) and histamine H1 receptor mRNA.
AB  - In the present study, we investigated the effect of interleukin-4 (IL-4) on
      metalloproteinase 1 (MMP-1/tissue collagenase) production in human rheumatoid
      synovial fibroblasts. Northern blot analysis revealed that addition of IL-4 with
      or without histamine stimulated the cells to increase the amount of proMMP-1
      mRNA, and the IL-4 with histamine addition resulted in a 3.3-fold increase
      compared with histamine only. Furthermore, IL-4 itself stimulated the expression
      of histamine H1 receptor mRNA. These results suggest that IL-4 may play an
      important role in joint destruction in RA.

PMID- 8988339
TI  - Age-related analysis of EcoRI generated satellite DNA-containing chromatin of rat
      liver.
AB  - EcoRI digestion of nuclei and their subsequent lysis with EDTA solubilizes 45%
      and 36% of chromatin DNA from the liver of young (18 +/- 2 weeks) and old (100 +/
      5 weeks) rats, respectively. After hybridization with 185 bp rat satellite I
      DNA, these soluble fractions are found to be enriched in specific DNA sequences
      such as satellite DNA. Besides regular repeat pattern, a major portion of the
      satellite chromatin forms higher order organization. Digestion kinetics confirms
      condensation of satellite DNA-containing chromatin similar to that of bulk
      chromatin in old age. Furthermore, densitometric scanning of the slot-blot of
      soluble chromatin fractions reveals loss of satellite DNA in the old. However, an
      increase in the linker histone H1 and its subfraction H1zero in the satellite DNA
      enriched fraction of chromatin from old rats suggests greater compaction. These
      results provide the first evidence that the satellite DNA-containing chromatin
      differs in the liver of young and old rats.

PMID- 8988340
TI  - cDNA sequence analysis of a novel cardiotoxin-like protein from Taiwan banded
      krait.
AB  - The cDNAs encoding a novel protein was constructed from the cellular RNA isolated
      from the venom glands of Bungarus multicinctus by reverse transcription
      polymerase chain reaction. The deduced amino acid sequence of this novel protein
      contained 65 amino acid residues with 8 cysteine residues. Comparative sequence
      analysis showed that it was structurally related to cardiotoxin rather than
      neurotoxins. These results suggest that the venom of Bungarus multicinctus may
      contain cardiotoxin(s) which was not noticed before.

PMID- 8988341
TI  - Bone mass homeostasis and bisphosphonate action.
AB  - The evidence supporting the concept of bone mass homeostasis controlled by
      mechanical loads is summarized. The well-known adaptation of bone structure to
      mechanical loads can only be achieved if an increase in load stimulates bone
      formation and a decrease stimulates bone resorption. This defines the feedback
      system that can play a role in the coupling of bone formation to bone resorption.
      The two processes are not determining bone mass, but serve as means to maintain
      it at the homeostatic level. Imbalance produced by excess resorption, which
      cannot be effectively matched by increased formation, a slower process, causes
      bone loss. Slowing of bone resorption can facilitate the restoration of bone mass
      to homeostatic levels and, since bone formation is mechanically driven, the newly
      evolving structure would best be suited for mechanical usage and should reduce
      the risk of fractures.

PMID- 8988342
TI  - Rapid nodule evaluation computer-aided image analysis procedure for bone nodule
      quantification.
AB  - Using bone cell cultures, the effects of drugs on cell activities such as
      proliferation, differentiation, matrix formation, and mineralization can be
      explored. To quantify these parameters accurately and quickly, a kinetic
      reproducible computed image analysis procedure of culture dishes is proposed
      which could be conjointly used with biochemical analysis of the medium. In the
      present article, different mathematical procedures coupled either with or without
      histochemical staining are investigated and analyzed. Using serial cross sections
      and microradiographies of bone nodules, we demonstrated that the gray-level
      parameter is well correlated with bone mass and/or the mineralization status of
      the nodules. The procedure selected is a multistep procedure called rapid nodule
      evaluation (RNE), which uses a binary reconstruction program with different
      thresholds. To challenge this RNE procedure with the classical Von Kossa staining
      and quantification procedure, we cultured the cells in the presence of 10 nmol/L
      dexamethasone and compared the results using the two procedures. The RNE
      procedure appeared to be accurate and reproducible, and also has the advantage of
      speed and dynamic analysis over the classical Von Kossa quantification procedure.

PMID- 8988343
TI  - Progesterone stimulates proliferation and differentiation of osteoprogenitor
      cells in bone cell populations derived from adult female but not from adult male
      rats.
AB  - We examined the effects of the synthetic glucocorticoid dexamethasone (Dex) and
      of the sex steroids progesterone (Prog) and testosterone (Testo) on proliferation
      and differentiation of progenitors for osteoblasts, adipocytes, and macrophages
      in cell populations derived from lumbar vertebrae of adult male and female rats.
      To assay for these progenitors, we used a previously described colony assay,
      where progenitors are identified by the appearance of colonies of the
      differentiated phenotype in long term cultures of cell populations containing
      these progenitors. In cell populations derived from both males and females, Dex
      (10(-9)-10(-6) mol/L) induced a similar dose-dependent increase in the number of
      osteoblast colonies (bone nodules), colonies of alkaline phosphatase (AP)
      positive cells, adipocyte colonies and macrophage colonies (ED2-positive cells).
      Prog (10(-8)-10(-5) mol/L), on the other hand, increased bone nodule formation in
      female-derived populations but not in male-derived populations. Maximal
      stimulation was seen at 10(-5) mol/L. 17 beta-Estradiol (E2) enhanced the Prog
      induced increase in the number of bone nodules in a dose-related fashion. Maximal
      stimulation was seen at 10(-8) mol/L E2. E2 (10(-9)-10(-6) mol/L) had no effect
      on Dex-induced bone nodule formation, indicating that the effect is specific for
      Prog-induced stimulation of bone nodule formation. Prog also caused a dose
      dependent increase in the number of colonies of AP-positive cells. Interestingly,
      the effect of Prog on the number of AP-positive colonies was the same in
      populations derived from both sexes. Prog-induced stimulation of adipocyte and
      macrophage development in female-derived populations was significantly greater
      than that in male-derived populations. Testo (10(-9)-10(-5) mol/L) had no effect
      on any of the parameters evaluated in populations derived from either males or
      females. These observations demonstrate that the effect of Prog on proliferation
      and differentiation of progenitors for osteoblasts, adipocytes, and macrophages
      in cell populations derived from lumbar vertebrae of adult male or female rats is
      sex-dependent and is seen either only (bone nodule formation) or more pronounced
      (adipocyte and macrophage development) in female-derived populations.

PMID- 8988344
TI  - Ovariectomy and orchidectomy induce a transient increase in the osteoclastogenic
      potential of bone marrow cells in the mouse.
AB  - Withdrawal of gender steroids in both women and men is associated with an
      increase in bone turnover with bone resorption exceeding bone formation leading
      to bone loss. To further investigate this process, the osteoclastogenic potential
      of mouse bone marrow cells was assessed at different timepoints after ovariectomy
      (ovx) or orchidectomy (orx). Cocultures of osteoclast-free fetal mouse long bones
      together with bone marrow from ovariectomized or orchidectomized mice indicated
      that the withdrawal of gender steroids in female and male mice induces a
      transient increase in osteoclastogenesis. The osteoclastogenic potential of the
      bone marrow cells was increased 7 days after ovx or orx. However, osteoclastic
      resorption was not increased at 3 days after surgery and had normalized 30 days
      after either ovx or orx. These results suggest that the withdrawal of gender
      steroids induces a transient increase in osteoclastogenesis in mice of both
      genders, which is associated with the early phase of rapid bone loss.

PMID- 8988345
TI  - Comparative effects of droloxifene, tamoxifen, and estrogen on bone, serum
      cholesterol, and uterine histology in the ovariectomized rat model.
AB  - The purpose of this study was to compare the effects of droloxifene (DRO),
      tamoxifen (TAM), and 17 alpha-ethynyl estradiol (EE) on bone mineral density,
      bone histomorphometry, total serum cholesterol, and uterine histology in the
      ovariectomized (ovx) rat model. Sprague-Dawley female rats at five months of age
      were sham-operated and treated orally with vehicle (n = 8), or ovx (n = 56) and
      treated (p.o.) with either vehicle, DRO at 0.1 or 1.0 mg/kg daily, TAM at 0.1 or
      1 mg/kg daily, or EE at 3 or 30 micrograms/kg daily for 4 weeks. The uterine wet
      weight and uterine histologic parameters (cross-sectional tissue area, stromal
      thickness, and luminal epithelial thickness) were determined. Femoral and lumbar
      vertebral bone mineral density was determined ex vivo using dual energy x-ray
      absorptiometry. Static and dynamic cancellous bone histomorphometry was performed
      on double-labeled, undecalcified longitudinal sections from proximal tibial
      metaphyses. Furthermore, the changes in total serum cholesterol and body weight
      gain were also determined. Compared to sham controls, ovx for four weeks
      significantly decreased uterine weight (-72%), uterine cross-sectional tissue
      area (-74%), stromal thickness (-52%), and luminal epithelial thickness (-53%).
      ovx rats treated with EE at 30 micrograms/kg/day maintained these parameters at
      the levels of sham controls. Uterine weight and uterine cross-sectional tissue
      area in 3 micrograms/kg/day of EE treated ovx rats were higher than that of
      vehicle-treated ovx rats. In ovx rats treated with TAM at both 0.1 and 1
      mg/kg/day, these parameters were significantly less than sham controls but
      significantly higher than ovx controls. DRO at 0.1 mg/kg/day had no effects on
      all above parameters. Uterine weight and cross-sectional tissue area in 1
      mg/kg/day of DRO treated ovx rats was slightly but significantly higher than that
      in ovx controls. However, DRO at 1 mg/kg/day had no effects on uterine stromal
      thickness and luminal epithelial thickness compared to ovx controls. The ovx
      induced decrease in femoral and lumbar vertebral bone mineral density was
      prevented by treatment with EE at 30 micrograms/kg/day, TAM at both 0.1 and 1
      mg/kg/day, or DRO at 1 mg/kg/day. Similarly, the decrease in bone mass and the
      increase in bone resorption and bone turnover in proximal tibial metaphyses were
      prevented by treatment with EE at 30 micrograms/kg/day or TAM at both 0.1 and 1
      mg/kg/day, or DRO at 1 mg/kg/day. Total serum cholesterol decreased significantly
      in ovx rats treated with either EE, DRO, or TAM at all dose levels compared to
      vehicle treated ovx controls (-32% to -56%). The ovx-induced body weight gain was
      completely prevented by EE at 30 micrograms/kg/day, and partially prevented by
      DRO at 1 mg/kg/day. TAM at both 0.1 and 1 mg doses caused a significant decrease
      in body weight compared to both sham and ovx controls. Our results indicated that
      DRO prevented ovx-induced bone loss and lowered total serum cholesterol with an
      ED50 less than 1 mg/kg/day. The bone protective and cholesterol lowering effects
      of DRO were comparable to those observed with TAM and EE. However, DRO differed
      from TAM and EE in its lack of significant estrogenic effects on uterine tissue
      at doses which were bone protective. These data suggest that DRO may be a
      significant alternative to EE and TAM for prevention and treatment of
      postmenopausal osteoporosis.

PMID- 8988346
TI  - Dexamethasone suppresses in vivo levels of bone collagen synthesis in neonatal
      mice.
AB  - The objective of this study was to determine the acute effects of glucocorticoids
      on in vivo levels of bone collagen synthesis in neonatal mice. Mice were injected
      with vehicle or dexamethasone at the start of the experiment. At 22 h, mice were
      given a 10 microCi injection of [3H]proline. At 24 h, the mice were sacrificed
      and the incorporation of [3H]proline into collagenase-digestible CDP labeling)
      and noncollagen (NCP labeling) protein in calvariae were determined by digestion
      with bacterial collagenase. Calvarial RNA was analyzed for COL 1A1 and
      osteocalcin mRNA levels by Northern blotting. After 24 h, vehicle-treated mice
      showed a 9.8 +/- 1.0% weight gain while dexamethasone-treated mice (1 mg/kg) had
      a 7.4 +/- 0.8% weight loss. Dexamethasone (1 mg/kg) decreased CDP and NCP
      labeling in calvariae by 51 +/- 4% and 17 +/- 4%, respectively (13 experiments).
      The inhibitory effect on protein labeling was selective for collagen since
      dexamethasone decreased the percent collagen synthesis from 25.4 +/- 1.6% to 16.6
      +/- 1.0% (13 experiments). Dexamethasone at 3 mg/kg also decreased CDP labeling
      and the percent collagen synthesis in calvariae. There was a 30% reduction in
      COL1A1 mRNA levels and a 67% decrease in osteocalcin mRNA levels. To determine
      the reversibility of the inhibition of collagen synthesis, mice were given a
      single injection of dexamethasone (1 mg/kg) and then injected with [3H]proline 2
      h prior to sacrifice at 24, 48, or 72 h. The reduction in CDP labeling observed
      at 24 h was fully reversed by 48-72 h. Moreover, by 72 h, the-rate of weight gain
      by dexamethasone-treated mice was similar to vehicle-treated controls. These data
      show that administration of dexamethasone to neonatal mice leads to a selective
      decrease in bone collagen synthesis within 24 h that is accompanied by down
      regulation of osteocalcin and COL1A1 mRNA levels. This model will be useful in
      determining mechanisms by which high dose glucocorticoids inhibit bone formation
      in vivo.

PMID- 8988347
TI  - Effects of strontium ions on growth and dissolution of hydroxyapatite and on bone
      mineral detection.
AB  - Preparation and analyses of a series of hydroxyapatites (HA) containing 1-10 mol
      % of Ca2+ replaced by Sr2+ is reported. The solubility of these apatites is found
      to increase with increasing content of Sr2+, 10% SrHA dissolves faster than CaHA
      at given values of Ca2+ and phosphate concentrations, but with a similar rate at
      the same degree of saturation. Sr2+ is found to inhibit the rates of both
      dissolution and growth of CaHA and 10% SrHA at pH 7.2, CaHA being more strongly
      inhibited by Sr2+ than 10% SrHA. The effect of partial substitution of Ca2+ in
      hydroxyapatite by Sr2+ on bone mineral content (BMC) and bone mineral density
      (BMD) measured by dual energy X-ray absorptiometry has been studied using three
      commercial densitometers. Extrapolating the absorption data for up to 10%
      replacement of Ca2+ by Sr2+ to 100% substitution of Ca2+ by Sr2+ in HA leads to
      an apparent increase in BMC or BMD of about a factor of 10. This factor is in
      agreement with theoretical calculations using attenuation coefficients of the
      atoms concerned. It is concluded that existing BMC scanners register artificially
      high values of BMC if the bone contains significant amounts of Sr2+ or other
      metal ions with atomic number larger than calcium.

PMID- 8988348
TI  - Time course of femoral neck osteopenia in ovariectomized rats.
AB  - To characterize osteopenic changes in the femoral neck of ovariectomized (ovx)
      rats, female Sprague-Dawley rats were ovx or sham operated upon at 3 months of
      age and killed at various times from 0 to 360 days postsurgery. Quantitative bone
      histomorphometry was performed on undecalcified longitudinal sections of the
      proximal femur from each rat. This skeletal site was found to be slowly growing,
      as its rate of longitudinal bone growth in 3-month-old baseline control rats (5
      microns/day) was nearly a factor of 10 less than that of a more commonly used
      sample site, the proximal tibia. In control rats, cancellous bone volume and
      cortical bone width of the femoral neck remained relatively constant, but
      cancellous mineral apposition rate declined with age during the course of the
      study. In contrast, cancellous bone volume in ovx rats was significantly
      decreased to 75%-82% of control level at 30-90 days and further decreased to 50%
      56% of control level at later times postovariectomy. Indices of cancellous bone
      turnover such as osteoclast and osteoblast surfaces and bone formation rate were
      markedly increased in ovx rats at 30 days, declined toward control levels by 90
      days, then increased moderately at 180-360 days. In comparison to control rats, a
      slight decrease in cortical width of the femoral neck was observed in ovx rats at
      180 days and reached statistical significance at 360 days postovariectomy.
      Endocortical bone formation rate was increased significantly in ovx rats compared
      with control rats at most time points. The results indicate that both cancellous
      and cortical osteopenia associated with high bone turnover occur in the femoral
      neck of ovx rats. Cancellous bone loss at this skeletal site is statistically
      significant as early as 30 days postovariectomy, but remains relatively moderate
      for the first 90 days before becoming more pronounced at later times after
      ovariectomy. In contrast, cortical osteopenia was not observed in the femoral
      neck of ovx rats until 1 year postovariectomy. This histomorphometric
      characterization of osteopenic changes in the femoral neck of ovx rats may serve
      as a basis for use of this slowly growing sample site in preclinical studies of
      the prevention and treatment of bone loss in the estrogen-depleted skeleton.

PMID- 8988349
TI  - Morning or evening administration of nasal calcitonin? Effects on biochemical
      markers of bone turnover.
AB  - The purpose of this study was to examine the effect of intranasal salmon
      calcitonin (sCT) administration (200 IE), given either in the morning (8:00) or
      evening (21:00), on the known circadian variation in biochemical markers of bone
      turnover. An open, placebo-controlled, randomized, crossover study, with three 24
      h studies of blood samples drawn every third hour and urine collected in 3 h
      aliquots was undertaken. Subjects consisted of nine healthy postmenopausal women,
      aged 58 +/- 7 years. Urinary CrossLaps (a measure of bone resorption) was
      measured by ELISA and corrected for creatinine (Cr). Serum osteocalcin (sOC) was
      measured by radioimmunoassay (RIA). The first 24 h study was performed without
      intervention. Prior to this control study the participants were randomized to
      either morning (8:00) or evening (21:00) sCT (200 IE). sCT administrations were
      given 4-5 days prior to and during the second study. After a washing-out period
      of 2 weeks the participants were given 200 IE of sCT at the reverse time of the
      day 5 days prior to and during the third study. At all timepoints, urinary
      CrossLaps/Cr exhibited a significant (p < 0.001) circadian rhythm with its zenith
      in early morning and nadir in late afternoon. Both morning and evening
      administration of sCT significantly decreased the urinary excretion of
      CrossLaps/Cr approximately 3-6 h after administration with a subsequent rebound
      effect. sOC did not exhibit a significant circadian variation and was not
      affected by the calcitonin. The 24 h mean urinary CrossLaps/Cr and sOC remained
      unchanged. Both morning and evening sCT significantly decreased the urinary
      excretion of CrossLaps/Cr 3-6 h after administration, with a rebound effect
      approximately 12 h later. However, the present study does not indicate that
      neither evening nor twice-daily administration is superior to morning
      administration.

PMID- 8988350
TI  - Evidence for secular change in Paget's disease.
AB  - Death certification data has shown that death rates due to Paget's disease of
      bone and osteosarcoma in older people (assumed to be attributable to Paget's)
      declined in the latter part of the 19th and in the early 20th century, suggesting
      that there may be a secular trend toward less severe disease. We have reviewed a
      21 year experience in a clinic specializing in Paget's disease. Data from all
      1041 patients attending the clinic in this period were reviewed. Despite an
      increase in the susceptible population and an increased rate of referral to the
      clinic over this time (p = 0.012), there was a fall in the absolute numbers of
      patients referred with severe disease, as judged by the initial plasma alkaline
      phosphatase activity at presentation. In the years 1973-1978 the initial plasma
      alkaline phosphatase was > 500 U/L in an average of 22 new patients per year and
      > 1000 U/L in 12 per year. In the years 1988-1993, the figures were 12 and 3 per
      year, respectively. During this period, there were no other facilities offering
      scintigraphy or intravenous treatment for Paget's disease in the Auckland region,
      making it unlikely that patients with severe disease were being seen and treated
      elsewhere. The average age of newly referred patients rose steadily from a mean
      62 years, in 1971-1973 to 71 years in 1991-1993 (p < 0.001). 534 subjects had
      scintiscans (52%) from which the extent of skeletal involvement was calculated.
      Skeletal involvement showed a significant negative correlation with year of birth
      (p < 0.01) but not with age or year of presentation. The proportion of patients
      with > 20% skeletal involvement had fallen by a third in the cohort born after
      1926, compared to the cohort born before 1915. Our data demonstrate that, on
      average, newly referred patients with Paget's disease have less severe disease
      and are significantly older at diagnosis than was the case two decades ago.

PMID- 8988351
TI  - The accumulation of whole body skeletal mass in third- and fourth-grade children:
      effects of age, gender, ethnicity, and body composition.
AB  - The purpose of this longitudinal study is to describe bone mass and body
      composition, and the annual changes in these measurements, among third grade
      students recruited from a suburban school district. Whole body bone mineral
      content (WBBMC), bone mineral density (WBBMD), fat, and lean mass were measured
      by dual-energy X-ray absorptiometry. Bone mass in the lumbar spine (LBMC) region
      of the whole body scan was also utilized. 773 students (38% white, 57% black, 5%
      other) had baseline visits; 561 had a second measurement a year later. At
      baseline, black children have significantly higher WBBMC, WBBMD, height, and lean
      mass than whites. Black males, but not black females, have a greater LBMC. There
      are no significant gender differences in body size, WBBMC, or WBBMD, although
      girls have a greater LBMC and fat mass, and boys have a higher lean mass. Most of
      these differences persist in visit 2. The annual change in bone and lean mass is
      greater in blacks. Stepwise linear regression analyses of bone mass on body size,
      gender, and ethnicity and their interactions indicate that log-transformed weight
      explains most of the variance in both WBBMC and WBBMD (multiple r2 = 0.90 and
      0.64, respectively). There are significant black/white differences in intercepts
      and slopes. Other variables explain only another 1%-2% of the variance. The
      strongest Pearson correlations are between changes in bone mass and changes in
      lean mass and log-transformed weight (r ranging from 0.62 to 0.84, p = 0.0001).
      We conclude that there is a significant black/white, but not male/female
      difference in whole body bone mass and bone density before puberty. Ethnic and
      gender differences in bone and body composition suggest that the lean component
      may contribute to a greater peak bone mass in blacks vs. whites, and perhaps in
      males vs. females.

PMID- 8988352
TI  - Insect-resistant tobacco plants expressing insect-specific neurotoxin AaIT.
AB  - The recombinant plant expression vector pNGY-2 with designed and synthesized AaIT
      gene had been constructed. The AaIT gene was fused behind the sequence of TMV and
      inserted into expression vector under the control of two linked 35s promoters.
      The recombinant plasmid pNGY-2 was transferred into tobacco NC89 by agrobacterium
      mediated transfer system. The GUS activity analysis and Southern blotting of
      regenerated plants indicated that AaIT gene had been integrated into tobacco
      genome. Insect bioassays showed that some transgenic plants had notable insect
      resistant activity.

PMID- 8988353
TI  - The cloning, sequence analysis, and expression in E. coli of coat protein gene of
      grapevine fanleaf virus Gh.
AB  - Fragments of 5' end and 3' end of the coat protein gene of a Chinese strain
      grapevine fanleaf virus (GFLV-Gh) were separately amplified through RT-PCR. The
      two products were cloned and ligated into a complete full-length coat protein
      gene via an inherent BgIII restriction site. The entire gene contains 1512
      nucleotides which encode a 504 amino acids coat protein, molecular weight
      approximately 56 kDa. Comparison with GFLV F-13 shows 88.4% homology in
      nucleotides and 95.8% similarity in deduced amino acid residues. Also this coat
      protein gene was expressed in E. coli DH 5 alpha.

PMID- 8988354
TI  - Preparation, cloning, and high level expression in E. coli of interleukin 2
      pseudomonas exotoxin fusion genes.
AB  - Using PCR and oligonucleotide-directed mutagenesis, recombinant plasmids which
      express IL2-PE fusion genes, e.g., IL2-PE40, IL2-PE40 KDEL, IL2-PE66(4Glu), and
      IL2-PE66(4Glu) KDEL, were constructed and expressed in E. coli at a high level.
      The fusion proteins were 20-30% of the total soluble bacterial proteins, existing
      as inclusion bodies in the host cell. In addition, there are single EcoRI, PstI,
      and SmaI restriction sites at the 5', 3' terminals and the linking region of the
      fusion genes, respectively, in the constructed expression plasmids so that these
      vectors could be conveniently converted to other expression vectors containing
      other cytokines or toxins.

PMID- 8988355
TI  - Construction of a stable and non-resistant bivalent vaccine candidate strain
      against Shigella flexneri 2a and Shigella sonnei.
AB  - The E. coli cs3 gene coding for CFA/II antigen was site-specifically integrated
      into the asd gene locus of S. flexneri 2a vaccine strain T32, resulting in the
      inactivation of the asd gene. Meanwhile, the gene cluster for S. sonnei O antigen
      was cloned into a non-resistant expression vector pXL378 to construct the plasmid
      pXL390. By transforming the asd-mutant of the T32 strain with pXL390, the
      bivalent vaccine candidate strain FS01 against S. flexneri 2a and S. sonnei was
      finally obtained. Experiments showed that the recombinant plasmid pXL390 was very
      stable in the asd-T32 strain without the use of any antibiotics; the FS01 strain
      was genetically stable and expressed two kinds of Shigella LPS-O antigens on the
      surface without any enhancement of its toxicity. Animal tests demonstrated that
      FS01 strain, when administered subcutaneously in mice, could provide 100%
      protection against the intraperitoneal challenges of virulent S. flexneri 2a and
      S. sonnei.

PMID- 8988356
TI  - Construction of a stable expression vector carrying sop genes [ZJ1].
AB  - Mini-F, the fifth fragment of F plasmid from EcoRI digestion, is known to carry
      an efficient partitioning function. Two pBR322 plasmid derivatives, pDMC32 and
      pDMC311, have been constructed from this fragment. The plasmid pDMC32 carries all
      the relative genes for plasmid stability, ccd, repD, and sop genes (sopA, sopB,
      and sopC), along with oriS and oriV, while pDMC311 carries only sop genes (sopA,
      sopB, and sopC). The plasmid maintenance proportions for pDMC32 and pDMC311 in E.
      coli were 93% and 100%, respectively, after 100 generations continuous
      cultivation of cells harboring the derivatives, MI32 (pDMC32) and MI311
      (pDMC311), in a phosphate-limited basal medium. As a control, the maintenance
      proportion of plasmid pBR322 dropped down to a low of 10% at generation 55 of
      continuous cultivation of E. coli MIR322 (pBR322) in the same medium. In order to
      make a stable expression vector that carries only sop genes, plasmid pDMC40 was
      constructed by adding a trp promoter from pDR720 to pBR322. The stable expression
      vector pDMC48 was then derived from pDMC40 by inserting sop genes into it from
      pDMC311. The maintenance proportion of plasmid pDMC48 in E. coli was still 100%
      after 100 generations of continuous cultivation of cells harboring the plasmid in
      phosphate-limited basal medium.

PMID- 8988357
TI  - Study on bovine serum albumin recovery from reversed micellar solutions.
AB  - From near-infrared spectra, it was confirmed that CTAB/hexanol-octane reversed
      micellar solution is a suitable medium for BSA solubilization. The effects of
      various factors, e.g., PH, and the type and concentration of salt in stripping
      solution, on Bovine Serum Albumin (BSA) back extraction were studied. The
      suitable conditions for stripping have been ascertained, i.e., 1.0-2.0 mol/L KBr,
      pH = 4.3-4.9. Spectroscopic studies showed that no significant change is observed
      in the structure of the main chain of BSA after extraction and back extraction.
      In addition, the problem of how long the reversed micellar solution can be
      recycled has been examined. Finally, the recovery and concentration of protein
      were successfully obtained with suitable phase ratio.

PMID- 8988358
TI  - Studies on high-density cultivation of Vero cells with biosilon solid
      microcarrier.
AB  - From eight kinds of microcarriers, Biosilon has been chosen as the most suitable
      microcarrier for high-density cultivation of African green monkey kidney (Vero)
      cells. Conditions affecting high-density cultivation were studied with a 500 ml
      modified Wheaton spinner flask. When cultivation with a 1.5 L CelliGen bioreactor
      at inoculum density of 4.9 x 10(6)/ml and perfusion volume increased from 0.20 L
      to 3.65 L gradually, the cell density could reach 2.05 x 10(7)/ml after 22 days
      of cultivation. When Vesicular Stomatitis Virus (VSV) was inoculated into the
      cultures of 1.21 x 10(6) ml at the some MOI (multiplicity of infection), the
      virus titers reached 7 log TCID50/ml and 8 log TCID50/ml, respectively.

PMID- 8988359
TI  - Cloning and function determination of promoter region of glucoamylase gene from
      Aspergillus niger T21.
AB  - A 850 bp fragment of the 5' flanking region of the glucoamylase gene (glaA) was
      synthesized from A. niger T21 genome using PCR. The function detection vector was
      constructed by fusing this fragment to E. coli hygromycin B phosphotransferase
      gene (hph) and was used to transform A. niger. The high hygromycin resistance
      transformants thus obtained verified that the synthesized fragment functioned as
      a promoter in filamentous fungi. Southern blot analysis showed the hph gene has
      been integrated into genomic DNA of A. niger transformant.

PMID- 8988360
TI  - Study on the column process of adsorption decolorization for monosodium glutamate
      solution in fluidized beds.
AB  - The adsorption decolorization of monosodium glutamate solution employed in
      multiple column fluidized beds in a series is studied. The equilibrium data, the
      mass transfer kinetics, and fluid flow parameters are determined. A mathematics
      model taking into account the effects of particle size classification, particle
      size distribution, external and internal diffusions, and axial mixing in the
      liquid and solid phases is proposed, and the simulated results are in good
      agreement with the experimental data.

PMID- 8988361
TI  - Sequencing 39,350 bp of Saccharomyces cerevisiae chromosome XII utilizing ordered
      shotgun libraries.
AB  - A 39,350 bp cosmid containing DNA of Saccharomyces cerevisiae chromosome XII was
      sequenced by making use of ordered sub-clones of 1 kb insert-length selected from
      a physical clone map. In a first analysis, 96 clones were sequenced from both
      ends (10 gels) with two standard sequencing primers covering 91% of the total
      sequence (49% double-stranded). After selection of another eight clones six gaps
      of a total of 1.8 kb and several single-stranded stretches remained. These gaps
      were closed by 86 primer walks leading to an overall redundancy of 4.4 per base
      and a total of 292 sequencing reactions. The number of walking primers can be
      reduced significantly by more uniform clone lengths and longer sequencing reads,
      thus, the total amount of sequencing reactions can approach the minimum value
      achieved with primer walking strategies, with only very few walking primers
      needed for gap closure.

PMID- 8988363
TI  - Genetic analysis of the acetan biosynthetic pathway in Acetobacter xylinum:
      nucleotide sequence analysis of the aceB, aceC, aceD and aceE genes.
AB  - Sequence analysis of a 5.323 kb chromosomal DNA fragment from Acetobacter xylinum
      involved in the biosynthesis of the exopolysaccharide acetan, revealed the
      presence of four ace genes designated aceB, aceC, aceD and aceE. Comparison of
      translated gene sequences to the databanks was used to assign putative gene
      functions. AceB displayed strong homology to a glucose-diphosphoprenyl beta, D
      glucose transferase from Xanthomonas campestris, while AceC was homologous to a
      cellobiosyl-diphosphoprenyl alpha, D-mannose transferase from the same organism.
      Thus these genes encode enzymes catalyzing the second and third steps of the
      acetan biosynthetic pathway. AceD and AceE were homologous to ExoP and ExoT
      respectively from Rhizobium meliloti and are likely to be involved in acetan
      polymerization and export.

PMID- 8988362
TI  - DENN, a novel human gene differentially expressed in normal and neoplastic cells.
AB  - A novel 5843 bp human cDNA sequence was isolated from fetal liver cDNA using the
      RACE procedure. Within this cDNA was characterised an uninterrupted ORF of 3861
      nt encoding a predicted hydrophilic protein of 1287 aa with a calculated
      molecular mass of 141790 Da and an isoelectric point of 5.41. An RGD cellular
      adhesion motif was identified within the putative serine- and leucine-rich
      protein. Northern blot hybridisation with a specific cDNA probe revealed
      differential levels of expression of 6.5 kb transcripts in 35 human tissues and
      cancer cell lines, with strongest signals observed in fetal brain and kidney;
      adult testis, ovary, brain and heart; and in the SW480, K-562, HeLa S3 and HL-60
      cell lines. To reflect this feature, the novel gene was designated DENN for
      differentially expressed in normal and neoplastic cells. Furthermore, an
      alternative splicing event within DENN involving a 129 nt alternative exon
      encoding 43 aa was found in fetal liver and in several human cancer cell lines.
      Based on the predicted aa sequence, two peptides were designed and synthesised to
      raise rabbit polyclonal antisera which detected a distinct protein band of 140
      145 kDa in Western blots of human cell lines. Immunofluorescent labelling of
      human cells with the same antibodies indicated predominant cell membrane
      localisation with some cytoplasmic staining.

PMID- 8988364
TI  - Sequence of the 5'-flanking and 5'-UTR regions of the rat endothelin-A receptor
      gene.
AB  - Endothelin receptors bind peptides of the endothelin family, the most potent
      vasoconstrictors known, and have been implicated in hypertension. To begin to
      define DNA sequences necessary for the transcriptional regulation of the rat
      endothelin type A receptor (ETA), we have sequenced the 5'-untranslated region
      (UTR) and part of the 5'-flanking region, a total of 1153 nucleotides. Comparison
      of the rat and human sequences revealed a 57% similarity in the 5'-flanking
      sequences, and a 63% similarity in the 5'-UTRs. Several conserved sequences were
      identified, including GATA and E-boxes, which may be important for the regulation
      of ETA gene expression. Primer extension analysis identified two transcription
      initiation sites within the rat gene.

PMID- 8988365
TI  - Identification and sequences of the Treponema pallidum mglA and mglC genes.
AB  - Treponema pallidum, the agent of syphilis, cannot be continuously cultivated in
      vitro. To identify treponemal genes encoding exported proteins, we performed
      TnphoA mutagenesis of a T. pallidum genomic DNA library in Escherichia coli.
      Clone 6D2 was chosen for further study based on partial nucleotide sequence
      obtained from p6D2 containing a TnphoA insertion. A complete open reading frame
      (orf1) and a truncated orf (orf2) were identified in the treponemal DNA of p6D2.
      Orf1 encodes a hydrophobic protein of 531 amino acids with a calculated M(r) of
      57,882 Da. The deduced amino acid sequence of Orf1 has homology to the MglC
      proteins of E. coli, Haemophilus influenzae, and Salmonella typhimurium. T.
      pallidum Orf1 (MglC) contains a conserved motif that is found in integral
      cytoplasmic membrane proteins of ATP-binding cassette (ABC) transport systems. T.
      pallidum orf2 encodes a protein of 496 amino acids with a calculated M(r) of
      55,547 Da. The deduced amino acid sequence of Orf2 has homology to the MglA
      proteins of S. typhimurium, E. coli, H. influenzae, and Mycoplasma genitalium.
      Orf2 (MglA) contains two consensus ATP-binding motifs. T. pallidum mglA and mglC
      are located downstream of mglB, consistent with the gene order of previously
      identified mgl operons. The putative T. pallidum mgl operon encodes the first
      high-affinity ABC transport system identified in this spirochete.

PMID- 8988366
TI  - Nucleotide sequence of ribosomal protein L3 cDNA and the exon-intron structure of
      L3 gene in the nematode, Caenorhabditis elegans.
AB  - A cDNA and a gene encoding the nematode (C. elegans) ribosomal protein L3 have
      been cloned and sequenced. The nearly full-length cDNA is 1255 bp in size except
      for the poly (A) tail. The encoded protein consists of 401 amino acids and has
      calculated molecular weight of 45,657 daltons. The gene sequence determined is
      1649 bp and consists of four exons. The sequence of the nematode protein shows
      high homology to other eukaryotic proteins.

PMID- 8988367
TI  - Novel DNA probes capable of discriminating indica and japonica rice cultivars.
AB  - We obtained two DNA clones, G93 (1.6kb) and G318 (1.7kb) from indica rice (Oryza
      sativa L.) cultivar Culture 340. Southern hybridization analysis indicated that
      both DNA probes hybridized with DNA of indica cultivars but not with japonica
      cultivars. Some javanica cultivars DNAs did not hybridize with these probes.
      Nucleotide sequence (400bp) of a part of G93 showed a 65.8% G + C content. These
      novel DNA probes can be used for the study of evolutional fingerprinting of rice
      cultivars.

PMID- 8988368
TI  - Molecular structure of the mouse amelogenin genomic DNA.
AB  - A genomic DNA clone (14.5 kbp) for amelogenin, a tooth enamel specific protein,
      has been isolated from a mouse genomic library. The nucleotide structure of this
      DNA was determined by the polymerase chain reaction and sequence analysis. The
      result indicated that the cloned DNA contained all the exons in addition to
      approximately 5.5 kbp of upstream sequence.

PMID- 8988369
TI  - Molecular cloning of a hemopexin-like cDNA from rainbow trout liver.
AB  - Hemopexin is an abundant heme-binding serum protein synthesized in the liver and
      for which the sequence is determined only for mammals. Little is known about fish
      heme-binding proteins. We have cloned a rainbow trout complementary DNA that
      encodes a 445 amino acid polypeptide exhibiting an overall 30% homology with
      human hemopexin and 69% with the goldfish warm temperature acclimation-related 65
      kDa protein. Structural homology, deduced from hydrophobic cluster analysis
      (HCA), was strong between the trout and human proteins since global HCA scores of
      76% were obtained when the N- or C-terminal halves of the two proteins were
      compared. Moreover, several characteristics of hemopexin were found in the trout
      protein; finally, the trout hemopexin-like messenger RNA was specifically
      expressed in the liver. We conclude that the trout protein is a good candidate
      for a true fish hemopexin.

PMID- 8988370
TI  - Identification of genes encoding for peptide synthetases in the gram-negative
      bacterium Lysobacter sp. ATCC 53042 and the fungus Cylindrotrichum oligospermum.
AB  - Genes encoding for the multifunctional peptide synthetases lysobactin synthetase
      and peptolide SDZ 214-103 synthetase were identified by hybridization of genomic
      libraries with oligonucleotides derived from consensus motifs of various genes
      encoding for delta-(L-alpha amino-adipoyl)-L-cysteinyl-D-valine (ACV) synthetases
      and gramicidin S synthetase. The sequence of subcloned gene fragments revealed
      core motifs and a modular structure typical for the family of peptide synthetase
      genes. A fragment of 4.6 kb of the lysobactin synthetase gene was sequenced and
      one amino acid activating module was localized. The cloning of lysobactin
      synthetase was verified by marker-exchange mutagenesis and the lysobactin minus
      phenotype of the mutant. The sequenced 3.1 kb fragment of peptolide SDZ 214-103
      synthetase contained parts of two modules and was highly homologous to
      corresponding regions of module 6 and 7 of cyclosporin synthetase. Therefore, the
      localized modules may activate the amino acids threonine and glycine.

PMID- 8988371
TI  - Cloning and sequencing of an ovine interleukin-5 cDNA.
AB  - Interleukin-5 (IL-5) is a T-cell derived cytokine which stimulates eosinophil
      production and activation in human, mice and sheep. IL-5 is active as a growth
      factor for mouse but not human B cells. The role of IL-5 on ruminant B cells has
      not been clearly defined. By hybridisation with human IL-5 cDNA, the ovine IL-5
      gene was isolated from a liver genomic library. The IL-5 cDNA was obtained by
      reverse-transcriptase PCR using primers designed from the 5' and 3' coding
      sequence derived from the ovine IL-5 gene. The sequences of the cDNA shows that
      there is 79% and 73% nucleotide homology with the human and mouse sequences. The
      ovine IL-5 cDNA encoded a protein of 132 amino acids and the level of amino acid
      homology with human and mouse IL-5 is 64% and 56%, respectively. Two cysteine
      residues are conserved in ovine, human and mouse IL-5. There are two potential N
      linked glycoyslation sites in ovine IL-5.

PMID- 8988372
TI  - Cloning, DNA sequence, and regulation of expression of a gene encoding beta
      galactosidase from Lactococcus lactis.
AB  - The beta-galactosidase from Escherichia coli is one of the most important enzymes
      in molecular biology. Here we report the cloning and sequencing of a gene
      encoding beta-galactosidase from Lactococcus lactis and compare the predicted
      amino acid sequence to that from other organisms. The beta-galactosidase from L.
      lactis was found to be a protein of 996 residues with 68.7% similarity to the E.
      coli enzyme and 65.8% similarity to the enzyme from Klebsiella pneumoniae. The
      lactococcal beta-galactosidase has lower similarity (approx 55%) to the enzymes
      from other lactic acid bacteria and no significant similarity to the beta
      galactosidase enzymes from Agrobacterium radiobacter, Bacillus
      stearothermophilus, or Clostridium thermosulfurogenes. Expression of the lacZ
      gene from L. lactis was found to be higher when cells were grown in medium
      containing lactose than when grown in glucose, and expression was higher when
      cells were grown at 30 degrees C than at 35 degrees C.

PMID- 8988373
TI  - Identification of the bacteriophage T5 dUTPase by protein sequence comparisons.
AB  - It is shown by protein sequence comparisons that a 148 amino acid open reading
      frame (ORF 148) located at 67% of the bacteriophage T5 genome encodes a protein
      with strong similarity to known dUTPases. This protein contains five
      characteristic amino acid sequence motifs that are common to the dUTPase gene
      family. A similarity in size and high degree of sequence identity strongly
      suggest that the protein encoded by the ORF 148 of bacteriophage T5 is dUTPase.

PMID- 8988374
TI  - Cloning, nucleotide sequence, and functional expression of the Escherichia coli
      enolase (eno) gene in a temperature-sensitive eno mutant strain.
AB  - The entire Escherichia coli eno gene was cloned by functional complementation of
      a newly isolated temperature-sensitive enolase mutant and its nucleotide sequence
      determined. The deduced amino acid sequence is homologous to other known
      prokaryotic or eukaryotic enolases and amino acid residues, assumed to be
      involved in substrate or cofactor binding and catalysis, were found to be
      strictly conserved among all enolase proteins. Expression of the eno gene under
      the control of the lac promoter/operator resulted in an IPTG-inducible production
      of enzymatically active enolase in wild-type and enolase mutant strains.

PMID- 8988375
TI  - Characterisation of the chicken Cu,Zn superoxide dismutase gene.
AB  - A PCR product was generated from embryonic chicken spinal cord cDNA using primers
      designed to conserved regions of the human and bovine amino and carboxyl-terminal
      coding sequences of the Cu,Zn superoxide dismutase (SOD1, EC 1.15.1.1) gene. DNA
      sequencing confirmed this product to be the chicken homologue of the SOD1 gene.
      This sequence was compared to SOD1 from bovine, human and Xenopus laevis.
      Important structural features of SOD1 are shown to be conserved in the chicken
      gene.

PMID- 8988376
TI  - Sequence analysis of the 5.8S ribosomal DNA and internal transcribed spacers
      (ITS1 and ITS2) from five species of the Oxalis tuberosa alliance.
AB  - The internal transcribed spacer region (ITS1 and ITS2) of the 18S-25S nuclear
      ribosomal DNA sequence and the intervening 5.8S region from five species of the
      genus Oxalis was amplified by polymerase chain reaction and subjected to direct
      DNA sequencing. On the basis of cytogenetic studies some species of this genus
      were postulated to be related by the number of chromosomes. Sequence homologies
      in the ITS1, 5.8S and ITS2 among species are in good agreement with previous
      relationships established on the basis of chromosome numbers. We also identified
      a highly conserved sequence of six bp in the ITS1, reported to be present in a
      wide range of flowering plants, but not in the Oxalidaceae family to which the
      genus Oxalis belongs to.

PMID- 8988377
TI  - GTG as translation initiation codon in the apocytochrome b gene of sunflower
      mitochondria.
AB  - Sunflower mitochondrial DNA contains a single copy of the cob gene. The gene
      begins with the unusual GTG initiation codon and lies in a transcription unit
      having a different organization with respect to that common to the other six
      known sequences from plant species which include both monocotyledons and
      dicotyledons.

PMID- 8988379
TI  - The benefits of school screening for scoliosis in the central part of The
      Netherlands.
AB  - The Netherlands has well-organized school health services, and children are
      assessed on a regular basis for scoliosis among other disturbances and
      pathologies. The purpose of this study was to assess the benefits of an annual
      screening programme for scoliosis in the Netherlands. Three cohorts of 10,000
      children sampled at 10, 12 and 14 years of age, respectively, were followed for 3
      years. Children with a positive bending sign were referred to a second screening
      stage, in which external asymmetry was quantified. Children diagnosed via the
      programme (group 1) were compared with those children who had been referred for
      treatment independently of the screening (group 2). The total number of children
      in these groups combined was then compared with the number that would have been
      expected on the basis of accepted prevalence figures for idiopathic scoliosis
      given in current literature. Over 30,000 children were screened. Although the
      programme established a total of 57 cases of definite scoliosis (0.18%), the 34
      cases (0.11%) already known, mainly detected by previous school health checks,
      were more severe regarding the risk of progression and treatment. The annual
      screening programme did not detect a single case that needed surgery. These
      figures provide the basis on which to decide for or against adopting an annual
      screening programme for scoliosis; the decision is a socio-political one. Based
      on this study, we expect all scoliotic patients needing treatment should be
      detected in time if periodic health checks will be maintained biennially. On
      medical grounds, it is our view, that screening for scoliosis should not be
      performed in the Netherlands annually.

PMID- 8988378
TI  - Idiopathic scoliosis: biomechanics and biology.
AB  - For whatever reason, right-left asymmetry has attracted an illogical proportion
      of research effort. Non-structural scoliosis, for example secondary to a leg
      length inequality, is indeed a problem of right-left asymmetry, but structural
      scoliosis is a complex three-dimensional deformity involving all planes.
      Biomechanical, biological and clinical evidence indicates clearly that the
      problem is one of front-back asymmetry and not right-left. The importance of
      biological factors lies in their ability to bring the spinal column to and beyond
      its buckling threshold. Thus a taller and more slender spine is more liable to
      bend and, being stiffer in the sagittal plane, favours movement into other
      planes. This epitomises the spine of the scoliosis patient who is growing faster
      with a spinal template similar to other family members allowing idiopathic
      scoliosis to express itself genetically. It is the opposite condition to
      idiopathic hyperkyphosis (Scheuermann's disease), but this deformity is
      rotationally stable, thus remaining in the sagittal plane. The presence of an
      adjacent area of lordo-scoliosis below the region of hyperkyphosis testifies to
      the common nature of the pathogenesis of idiopathic scoliosis and Scheuermann's
      disease. It is the area of compensatory hyperlordosis below the Scheuermann's
      area that has obligatorily buckled and represents a human model supporting the
      lordosis theory, as does surgically tethering the back of the young growing human
      spine, which crankshafts accelerated progression. Similarly the only successful
      animal model of the formation of idopathic follows creation of a lordotic spinal
      segment in an otherwise kyphotic spine. For centuries, engineers have recognised
      that the mechanical behaviour of a column under load is influenced by geometry,
      as well as by material properties; it is clear that the spinal column also obeys
      these well-described laws.

PMID- 8988380
TI  - Spinal imbalance and decompensation problems in patients treated with Cotrel
      Dubousset instrumentation.
AB  - The basic principles of current idiopathic scoliosis treatment are three
      dimensional correction and rigid fixation. Although it is accepted that Cotrel
      Dubousset instrumentation (CDI) meets these goals, there is concern about the
      potential risk of trunk imbalance and spinal decompensation during the derotation
      manoeuvre. The results of 45 patients with idiopathic scoliosis treated with CDI
      between December 1988 and August 1992 were retrospectively analysed. Mean age was
      14.3 years and mean follow-up period was 48.6 months. An average correction of
      49.6% was achieved in the major curves. The best results were obtained in King
      type III curves, with a 69.4% correction. Spinal imbalance was evaluated by
      measuring lateral trunk shift (LT), shift of head (SH) and shift of stable
      vertebra (SS). Decompensation was measured by the increase in secondary curves.
      When all curve types were included, the average preoperative LT value of 1.96
      vertebral units (VU) was brought down to 0.91 VU postoperatively, achieving a
      55.9% correction. Fourteen patients had an SH value of zero preoperatively and
      remained balanced after instrumentation. Of the 41 remaining patients, 21
      achieved an SH value of zero postoperatively. When all cases were included, the
      average preoperative SH value was 1.0 VU, which was corrected to 0.42 VU with CDI
      (69% correction). An average correction of SS of 75.5% was obtained, with the
      mean preoperative value of 0.73 VU being corrected to 0.19 VU. At the last follow
      up visit, a secondary curve had formed above the major curve in one patient, and
      three patients had a junctional kyphosis. Loss of correction in the frontal plane
      correlated with loss of correction of LT. The rigid and semiflexible lumbar
      curves had a tendency to progress when they were not instrumented, especially in
      type II curves. Junctional kyphosis could be prevented when concave laminar claws
      were used in the thoraco-lumbar region. It was concluded that spinal
      decompensation and imbalance could be minimized with careful preoperative
      planning, avoidance of overcorrection and use of long instrumentation in double
      major curves.

PMID- 8988381
TI  - The segmental effect of Cotrel-Dubousset instrumentation on vertebral rotation,
      rib hump and the thoracic cage in idiopathic scoliosis.
AB  - The segmental effect of Cotrel-Dubousset instrumentation (CDI) on the spine and
      thoracic cage was investigated in 38 patients with adolescent idiopathic
      scoliosis by preoperative and postoperative postero-anterior and lateral
      radiographs and computed tomography from T1 to S1. Mean Cobb angle decreased by
      67%. The T5-T12 kyphosis in the hypokyphotic patients increased on average by 8.4
      degrees (P < 0.001). Average preoperative as well as postoperative maximal
      vertebral rotation was located at the apex level, and was reduced from 19.0
      degrees to 14.3 degrees (P < 0.001). All vertebrae between the upper and lower
      instrumented vertebrae were significantly derotated. Average derotation for the
      apical zone was 4.8 degrees (P < 0.001), for the upper instrumented zone it was
      2.5 degrees (P < 0.01), and for the lower instrumented zone it was 2.6 degrees (P
      < 0.01). Vertebral derotation was significantly higher in the apical zone than in
      the upper and lower instrumented zones. The apical rib hump index (RHi) decreased
      by 38% (P < 0.001) and the cumulative RHi for the five apical levels decreased by
      34% (P < 0.001). The RHi for the two levels above and below the instrumentation
      each decreased by 20% (n.s.). No significant increase in sagittal or transverse
      rib cage diameter at any level was observed. The translation in the coronal plane
      of the apical vertebra of major right thoracic curves improved significantly (P <
      0.001). The preoperative flexibility index of the major curve correlated
      positively (r = 0.47) with derotation at the apex level (P < 0.01). However, no
      correlation was found between flexibility index and reduction of RHi at the apex
      level. Vertebral derotation did not correlate with reduction in RHi at any level.
      The study shows that CDI results in a postoperative three-dimensional improvement
      of the spine and a limited improvement of the thoracic cage, with no tendency
      towards a worsened deformity at any level within or outside the instrumentation.

PMID- 8988383
TI  - Development of an instrument for clinical evaluation after surgery for
      neuromuscular scoliosis.
AB  - Surgical treatment for neuromuscular scoliosis is effective for most patients.
      Although those afflicted constitute a heterogeneous group, the aim of surgical
      treatment is approximately the same for all patients: a spine balanced in the
      coronal and sagittal planes over a level pelvis. Surgery results in a more stable
      and straighter spine, which should in turn improve performance in different
      activities. Previous evaluations of surgery for neuromuscular scoliosis reported
      in the literature have focused primarily on Cobb angles; there are very few
      studies dealing with the ability to perform various activities. A new tool for
      evaluation was developed in several steps, starting with a telephone interview
      with patients who had undergone surgery and a literature search. The evaluation
      instrument was then developed, followed by a pilot study and validation of new
      parts of the instrument. The instrument focuses on performance components and on
      activity performance. Eight items are evaluated before and after surgery. These
      data are complemented by a questionnaire administered to the patient or relatives
      at follow-up. The new parts of the instrument were developed specifically for
      patients with neuromuscular scoliosis, and the data obtained have been shown to
      have a high correlation with established measures of activities of daily living
      of daily living). They should therefore provide us with useful information
      concerning functional gains as a result of surgery as well as the effect of
      surgery on activity performance.

PMID- 8988382
TI  - Rip hump correction and rotation of the lumbar spine after selective thoracic
      fusion.
AB  - In this study a series of 32 patients with idiopathic scoliosis, managed with
      selective thoracic fusion, was reviewed. Classified according to King and
      instrumented with the H-frame, the patients were evaluated for curve correction,
      rib hump correction and postoperative shift in lumbar rotation. Age and follow-up
      average 19.4 and 2.4 years, respectively. The 32 patients had an average primary
      and lumbar curve correction of, respectively, 66% (6.0% correction loss) and 53%
      (3.4% correction loss). The respective values for postoperative rib hump
      correction and shift in apical lumbar rotation averaged 8 degrees and 9.4 degrees
      in type II King curves 4.4 degrees and 3.5 degrees in type III and 11 degrees and
      -5 degrees in Type IV. Significant differences were noted between the curve types
      in rib hump correction and shift in lumbar rotation. The study showed that en
      bloc postoperative rotation of the compensatory lumbar segment, directed towards
      the rib hump, positively influences rib hump correction. This en bloc rotation of
      the unfused lumbar segments is induced by the correcting forces applied by the
      instrumentation. The unfused lumbar spine of a patient with a King type II curve
      shows a larger lumbar rotation shift and subsequent rib hump correction than that
      of a patient with a King type III curve. Together with factors such as lateral
      angulation, rib-vertebra angles and structural limitations, the rotational
      dynamics of the unfused lumbar spine seem to form an important component in the
      under-standing and surgical management of scoliosis.

PMID- 8988384
TI  - Results of surgical treatment of spinal thoracic and lumbar metastases.
AB  - The results of surgical treatment of vertebral metastases were evaluated from a
      retrospective review of a consecutive series of 100 patients, with special
      reference to anatomoclinical aspects and functional outcome. The primary tumour
      in most cases was lung, breast, or prostate; it was unknown in 11 cases.
      Diagnosis of the metastasis occurred 4-86 months after that of the primary tumour
      (lung metastasis: 4 months; breast metastasis: 86 months; prostatic metastasis:
      22 months). Patients complained of vertebral pain in 96 cases and/or radicular
      pain in 43 cases. Intractable pain was observed in lung metastasis in particular.
      All patients received analgesics, and 57 received morphinics. Walking was
      impossible for 50 patients. Thirty-eight patients presented with neurologic
      deficit; neurologic status varied according to the primary tumour. Treatment
      included anterior surgery in 58 patients, posterior surgery in 33 patients, and
      combined surgery in 9 patients. Mean duration of hospitalisation was 12 days. No
      patient was admitted to the intensive care unit. Mean follow-up was 13.5 months.
      Eighty-nine patients were dead at follow-up, with an average survival of 10
      months. Mean survival time was 7 months for patients with lung metastasis, 12
      months for those with breast metastasis and 24 months for those with prostatic
      metastasis. Ten patients were still alive at follow-up (mean follow-up period 45
      months, range 17-72 months). Analgesics were stopped for 62 patients following
      discharge from hospital. Morphinics had to be continued in seven patients. Thirty
      five patients out of 50 (70%) recovered walking capacity. Neurologic status
      improved in 30 out of 38 patients. Although duration of survival was limited,
      surgery proved to be beneficial in providing a significant and early improvement
      in the functional status of more than 80% of patients. A precise evaluation of
      preoperative pain is necessary. Pain is dependent upon the bony lesion, the
      primary tumour, and the tumoral topography, which defines the surgical approach.

PMID- 8988385
TI  - Ewing's tumor of the spine: report on seven cases including one with a 10-year
      follow-up.
AB  - This study analyzed the cases of seven patients who completed the Treatment
      Protocol of the University Clinic of Navarre for Ewing's tumor of the spine
      between 1982 and 1993. The surgical procedures aimed at gaining local control and
      recovering the neurological deficit are discussed. Poor results in the survival
      rate can be expected, as shown by the clinical study. Only two patients are
      alive, including one who is free of disease more than 10 years after surgery.

PMID- 8988386
TI  - Iatrogenic spinal infection following epidural anaesthesia: case report.

PMID- 8988387
TI  - Bacterial surface structures--an update.

PMID- 8988388
TI  - Phase-variable outer membrane proteins in Escherichia coli.
AB  - Escherichia coli contains at least two phase-variable proteins in its outer
      membrane. One, termed antigen 43 (Ag43), is the product of the metastable flu
      gene located at min 43.6 on the E. coli chromosome and is responsible for colony
      form variation and for autoaggregation in liquid media. Ag43 is composed of two
      proteinaceous subunits, alpha 43 and beta 43 in 1:1 stoichiometry. alpha 43
      (apparent M(r) 60,000) is surface expressed, extends beyond the O-side chains of
      smooth lipopolysaccharide and is bound to the cell surface through an interaction
      with beta 43 (apparent M(r) 53,000), itself an integral, heat-modifiable, outer
      membrane protein. alpha 43 shows limited N-terminal sequence homology with
      certain enterobacterial adhesins, and notable sequence homology with AIDA-1, an
      adhesin of diffuse-adhering E. coli. In addition, alpha 43 contains an RGD motif
      and a consensus sequence for an (autoproteolytic?) aspartyl protease active site.
      Expression of Ag43 is subject to reversible phase variation-in liquid minimal
      medium, the rates of variation from Ag43+ to Ag43- states and from Ag43- to Ag43+
      states being approximately 2.2 x 10(-3) and approximately 1 x 10(-3),
      respectively. Phase switching of Ag43 is regulated by DNA methylation
      (deoxyadenosine methylase (dam) mutants being 'locked OFF') and by OxyR (oxyR
      mutants being 'locked ON'). It is proposed that OxyR acts as a repressor of Ag43
      transcription by binding to unmethylated GATC sites in the regulatory region of
      the gene. In some strains, Ag43 may also undergo antigenic variation. A 94 kDa
      immunocrossreactive outer membrane protein, showing similar rates of phase
      variation, has additionally been detected for some enteropathogenic and
      uropathogenic strains of E. coli. This 94 kDa protein can be proteolytically
      cleaved in situ with trypsin to yield two membrane-bound products with M(r)s and
      properties similar to those of alpha 43 and beta 43. Results suggest that Ag43
      may represent one of a family of antigenically-related high-M(r) adhesins which
      are synthesized as polyprotein precursors. Some members may be processed and
      presented on the cell surface as bipartite protein complexes (as Ag43). Others
      can remain uncleaved.

PMID- 8988389
TI  - On the targeting and membrane assembly of the Escherichia coli outer membrane
      porin, PhoE.
AB  - Within gram-negative bacteria such as Escherichia coli, the outer membrane porins
      provide a relatively non-specific uptake route which is utilised by a wide range
      of solutes including many antibiotics. Understanding the targeting and membrane
      assembly of these proteins is therefore of importance and this mini review aims
      to discuss this process in light of present knowledge.

PMID- 8988390
TI  - Biochemistry and cell biology of bacterial endotoxins.

PMID- 8988391
TI  - Molecular mimicry of host structures by bacterial lipopolysaccharides and its
      contribution to disease.
AB  - The core oligosaccharides of low-molecular-weight lipopolysaccharide (LPS), also
      termed lipooligosaccharide (LOS), of pathogenic Neisseria spp. mimic the
      carbohydrate moieties of glycosphingolipids present on human cells. Such mimicry
      may serve to camouflage the bacterial surface from the host. The LOS component is
      antigenically and/or chemically identical to lactoneoseries glycosphingolipids
      and can become sialylated in Neisseria gonorrhoeae when the bacterium is grown in
      the presence of cytidine 5'-monophospho-N-acetylneuraminic acid, the nucleotide
      sugar of sialic acid. Strains of Neisseria meningitidis and Haemophilus
      influenzae also express similarly sialylated LPS. Sialylation of the LOS
      influences susceptibility to bactericidal antibody, may decrease or prevent
      phagocytosis, cause down-regulation of complement activation, and decrease
      adherence to neutrophils and the subsequent oxidative burst response. The core
      oligosaccharides of LPS of Campylobacter jejuni serotypes which are associated
      with the development of the neurological disorder, Guillain-Barre syndrome (GBS),
      exhibit mimicry of gangliosides. Cross-reactive antibodies between C. jejuni LPS
      and gangliosides are considered to play an important role in GBS pathogenesis. In
      contrast, the O-chain of a number of Helicobacter pylori strains exhibit mimicry
      of Lewis(x) and Lewis(y) blood group antigens. The role of this mimicry remains
      to be investigated, but may play a role in bacterial camouflage, the induction of
      autoimmunity and immune suppression in H. pylori-associated disease.

PMID- 8988392
TI  - Interactions of bacterial adhesins with extracellular matrix and plasma proteins:
      pathogenic implications and therapeutic possibilities.

PMID- 8988393
TI  - Fimbrial adhesins: similarities and variations in structure and biogenesis.
AB  - Fimbriae are wiry (2 to 4 nm diam.) or rod-shaped (6 to 8 nm diam.), fibre-like
      structures on the surfaces of bacteria which mediate attachment to host cells.
      Much has been learned in recent years about the biogenesis, structure and
      regulation of expression of these adhesive organelles in Gram-negative bacteria.
      Analyses of the genetic determinants encoding the biogenesis of fimbriae has
      revealed that the adhesive interaction of fimbriae can be mediated by major
      subunits (CFA/I and CS1 fimbriae) or minor subunits (P, S, and type 1 fimbriae),
      with the adhesin being located either at the tip of the fimbria or along the
      length of the fimbrial shaft. Minor subunits can also act as adapters, anchors,
      initiators or elongators. Post-translational glycosylation of the type 4 pilins
      of Neisseria gonorrhoeae, Neisseria meningitidis and Pseudomonas aeruginosa has
      been demonstrated. The structures of the PapD chaperone of Escherichia coli and
      of N. gonorrhoeae type 4 fimbrin have been resolved at 2.0-2.6 A. Rod-shaped
      fimbriae should not be thought of as being rigid inflexible structures but rather
      as dynamic structures which can undergo transition from a helicoidal to a
      fibrillar conformation to provide a degree of elasticity and plasticity to the
      fimbriae so that they can resist shear forces, rather like a bungee cord. At
      least four mechanisms have been identified in the assembly of fimbriae from
      fimbrin subunits, namely the chaperone-usher pathway (e.g., P-fimbriae of
      uropathogenic E. coli), the general secretion assembly pathway (e.g., type 4
      fimbriae or N-methylphenylalanine fimbriae of P. aeruginosa, the extracellular
      nucleation-precipitation pathway (e.g., curli of E. coli) and the CFA/I, CS1 and
      CS2 fimbrial pathway.

PMID- 8988394
TI  - Cell envelope characteristics of Helicobacter pylori: their role in adherence to
      mucosal surfaces and virulence.
AB  - Helicobacter pylori colonises the gastric mucosa of humans and causes both antral
      gastritis and duodenal ulcer disease. Exactly how H. pylori causes disease is not
      known but several pathogenic determinants have been proposed for the organism.
      These include adhesins, cytotoxins and a range of different enzymes including
      urease, catalase and superoxide dismutase. Surface molecules of H. pylori such as
      flagella, lipopolysaccharide, the urease enzyme and outer membrane proteins are
      putative adhesin molecules. While phosphatidylethanolamine and the Lewis(b) blood
      group antigen have been proposed as receptor molecules for the organism the exact
      mechanism by which H. pylori adheres to the gastric mucosa has still to be
      identified. Characterisation of the adhesins of H. pylori could lead to the
      development of adhesin analogues for use in the inhibition of colonisation and
      improved therapy for ulcer disease. In vivo studies with isogenic mutants which
      are incapable of adhering to the gastric mucosa would greatly clarify the
      significance of adherence. Such mutants could possibly be useful as a vaccine
      against infection with wild-type organisms.

PMID- 8988395
TI  - Peptide selection for presentation by HLA class I: a role for the human
      transporter associated with antigen processing?
AB  - Peptide epitopes presented by HLA class I are supplied by an elaborate system of
      antigen processing which subjects candidate epitopes to a process of selection
      according to little-understood rules. Transport of peptides from the cytosol into
      the endoplasmic reticulum by the TAP (transporter associated with antigen
      processing) complex is likely to play an important role in peptide selection for
      presentation. The recent development of an assay measuring substrate binding to
      the TAP complex has led to the identification of the major structural properties
      of peptides selected by the human transporter. Human TAP favors transport of
      peptides with structural features common to HLA class I ligands. However, TAP
      dislikes peptide ligands preferred by some HLA class I alleles, which may
      therefore frequently rely on alternative sources of peptide ligands.

PMID- 8988397
TI  - Immune system-neuroendocrine dysregulation in spinal cord injury.
AB  - Multiple communicative pathways among the nervous, endocrine and immune systems
      facilitate physiological immunoregulation. Spinal cord injury (SCI) patients have
      decreased natural (NK cell) and adaptive (T cell) immune function and reduced
      blood levels of cellular adhesion molecules (CAMs) that participate in immune
      function and wound healing. We found decreased LFA-1 and VLA-4 on peripheral
      blood leukocytes in SCI patients and lower levels of CAMs in SCI patients with
      pressure ulcers than in those without them. SCI might affect immune cells and
      immune responsiveness by: (1) disrupting the outflow of signals from the
      sympathetic nervous system to lymphoid tissues and their blood vessels as well as
      the returning afferent signals from these tissues to the brain; (2)
      immunosuppression caused by the stressors affecting SCI patients; (3)
      interrupting returning signals to the CNS from the periphery thereby reducing
      facilitation of immunoregulatory CNS neurons and decreasing their activity; or a
      combination of all three. SCI patients may develop dysregulation of the
      sympathetic nervous system that is intimately involved in immune function.
      Chronic stress mediates immunosuppression by corticosteroids, catecholamines,
      endorphins and met-enkephalin. The hypothalamus coordinates the response to
      stress through the release of soluble products from the sympathetic nervous
      system and hypothalamic-pituitary-adrenal axis. Whereas the nervous and endocrine
      systems are not concerned with immunological specificity, they do influence the
      intensity, kinetics and localization of immune responses. Products of an
      activated immune system may generate feedback circuits capable of inhibiting,
      enhancing or regulating neuronal input. Immune system cells can produce
      neurologically active peptides including ACTH, CRF, growth hormone, thyrotropin,
      prolactin, human chorionic gonadotropin, endorphin, enkephalins, substance P,
      somatostatin and VIP. Cytokines are likely important mediators of the HPA
      response to immune stimuli.

PMID- 8988398
TI  - Emerging cross-regulatory roles of immunity and autoimmunity in atherosclerosis.
AB  - Atherosclerosis is a histopathological process of a multifactorial origin.
      Whereas the genetic and biochemical causes received considerable attention, the
      involvement of the immune system has generally been considered negligible. In
      recent years evidence has been presented to support the dominant role played by
      the immune system in atherosclerosis. Two major antigenic determinants against
      which the immune response may be triggered have been suggested, namely the heat
      shock protein 60/65 and oxidized low density lipoprotein. The current paper
      reviews the data regarding the involvement of the immune system in atherogenesis
      with respect to the antigenic candidates mentioned above.

PMID- 8988400
TI  - Inflammatory mechanisms in the CNS: targets for therapeutic intervention.

PMID- 8988396
TI  - Class I HLA-restricted cytotoxic T lymphocyte responses against malaria-
      elucidation on the basis of HLA peptide binding motifs.
AB  - In animal models, CD8+ T cells are a critical effector mechanism in the
      protective immunity against malaria. Conventional approaches to the development
      of many vaccines, including those against malaria, have however proved
      inadequate. In particular, an alternative approach is needed for the development
      of vaccines designed to induce a cellular immune response mediated by CD8+ T
      cells. Advances in the field of molecular immunology during the past decade have
      provided an insight into the presentation of peptides by MHC class I molecules
      and their recognition by CD8+ T cells. These studies have provided a conceptual
      basis for the development of efficacious parasitic and viral vaccines. By a
      combination of immunochemical and cellular immunologic analyses based on specific
      peptide binding motifs, a subunit malaria vaccine that includes CD8+ T cell
      epitopes restricted by the most common class I HLA alleles, including HLA-A2, can
      now be constructed.

PMID- 8988401
TI  - Is local biotransformation the key to understanding the pharmacological activity
      of salicylates and gold drugs?
AB  - It is suggested that some drugs may be converted by inflammatory cells to yield
      active species. The transformation may be non-enzymatic, although being driven by
      the enzymatic production of highly reactive species which are normal products of
      activated leukocytes, such as singlet oxygen, hydrogen peroxide, hypochlorite,
      hydroxyl radical and nitric oxide. Drugs which may be transformed in this fashion
      are the anti-rheumatic gold complexes which may be converted either to
      aurocyanide or to Au(III) complexes by myeloperoxidase in polymorphonuclear
      leukocytes. Salicylate may also be activated by its oxidation to
      dihydroxybenzoates although evidence for its transformation is weaker than for
      the gold complexes.

PMID- 8988399
TI  - Experimental autoimmune uveitis: molecular mimicry and oral tolerance.
AB  - Intraocular inflammatory disease or uveitis, which affects the uveal tract and
      the retina of the eyes in human, is the major cause of visual impairment.
      Experimental autoimmune uveitis (EAU) is a T-cell-mediated autoimmune disease
      directed against retinal proteins and has been studied in several mammalian
      species including subhuman primates as a model for human posterior uveitis.
      Autoimmune responses provoked by molecular mimicry occur when the nonself and
      host determinants are similar enough to cross-react yet different enough to break
      immunological tolerance, and is one of the proposed mechanisms for induction of
      autoimmune diseases. Therapeutic immunomodulatory strategies have been used to
      induce antigen-specific peripheral immune tolerance in animal models of T-cell
      mediated autoimmune diseases by oral administration of autoantigens. Oral
      tolerance leads to unique mechanisms of tissue and disease-specific
      immunosuppression, which would circumvent the immunotherapeutic problem of
      multiple target tissue autoreactivity. Several groups have investigated the
      effects of delivering autoantigens across gastric mucosal surfaces. This review
      briefly discusses molecular mimicry and the mechanism of induction of oral
      tolerance with respect to immunopathogenesis of T-cell-mediated autoimmune
      disease in general and EAU in particular.

PMID- 8988402
TI  - Effects of three different Ca(2+)-ATPase inhibitors on Ca2+ response and
      leukotriene release in RBL-2H3 cells.
AB  - The effects of three Ca(2+)-ATPase inhibitors, thapsigargin (TG), cyclopiazonic
      acid (CPA), and 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ), on the Ca2+
      response, degranulation, and leukotriene C4 (LTC4) release in RBL-2H3 cells were
      investigated. All three compounds elevated the intracellular free Ca2+
      concentration ([Ca2+]i), and caused degranulation in the presence of 12-O
      tetradecanoylphorbol-13-acetate (TPA), a protein kinase C activator. The dose
      dependency of each compound in the Ca2+ response was in good agreement with that
      in degranulation. TG and CPA also caused the release of LTC4 in a dose-dependent
      manner, and this effect was unaffected by TPA or calphostin C, a selective PKC
      inhibitor. DTBHQ, however, did not induce LTC4 release, and rather inhibited the
      antigen-induced release of LTC4. These results suggest [1] that both
      degranulation and LTC4 release caused by these compounds are dependent on their
      [Ca2+]i increasing effect, [2] that degranulation and LTC4 release are mediated
      via independent pathways following the Ca2+ response, and [3] that DTBHQ
      additionally prevents the synthesis of LTC4 possibly by inhibition of 5
      lipoxygenase.

PMID- 8988403
TI  - Anti-inflammatory activity of topical nimesulide gel in various experimental
      models.
AB  - OBJECTIVE AND DESIGN: The anti-inflammatory activity of topically applied
      nimesulide gel was compared in different experimental models with that of
      diclofenac and piroxicam gels. MATERIAL: Wistar albino rats of either sex were
      used. TREATMENT: In acute models, 50 mg of nimesulide or diclofenac were applied
      to right hind paws 1 h (carrageenan) or immediately before (formalin) irritant
      injection (sub-plantar). In adjuvant arthritis, 50 mg of nimesulide, diclofenac
      or piroxicam were applied daily to injected paws for 14 days. METHODS: Paw volume
      was measured by plethysmograph. Statistical significance was tested with
      Student's t-test. RESULTS: In the carrageenan paw odema, topical nimesulide gel
      exhibited similar anti-inflammatory activity to diclofenac gel, and was more
      effective than diclofenac gel in formalin-paw odema. In both acute (18 h) and
      chronic (14 d) phases of adjuvant arthritis, nimesulide gel was more effective
      than diclofenac or piroxicam gels. CONCLUSION: Topical nimesulide gel possesses
      higher anti-inflammatory activity than that of diclofenac or piroxicam gels.

PMID- 8988404
TI  - Macrophage-colony forming cells (M-CFC), with different sensitivities to colony
      stimulating factors, from peritoneal exudates and tissues of chronically inflamed
      mice.
AB  - OBJECTIVE AND DESIGN: To determine whether nonadherent macrophage precursors are
      present within the inflamed peritoneal cavity in mice, we analysed the
      mononuclear cell populations from different peritoneal tissues. OBJECTS: A group
      of 90 female mice BDF1 (C57BL/ 6 x DBA/2) was used for the study. Mononuclear
      cells were harvested from the peripheral blood, bone marrow, peritoneal exudate,
      omentum, mesentery, parietal peritoneum and diaphragm. TREATMENT: Mice were
      injected intraperitoneally with 0.2 ml of Freund's incomplete adjuvant. Animals
      were sacrificed at 6, 13, 16, 21 and 30 days. Three to six animals were examined
      for each time period. METHODS: Progenitor cell assay was performed in 1 ml of
      semi-solid agarose (0.3% Seakem GTG) DMEM which was supplied either with
      recombinant colony stimulating factors or with mesothelial cell-conditioned
      medium. RESULTS: Nonadherent macrophage-colony forming cells were present in all
      peritoneal compartments (35-140 precursor cells/5 x 10(4) mononuclear cells).
      Granulocyte/ macrophage-colony forming cells were found in the inflamed omentum.
      Combined simultaneous treatment with GM-CSF and M-CSF blocked the proliferation
      of the exudate and mesentery-derived macrophage precursors, but not other
      peritoneal tissue-derived macrophage precursors. Sequential stimulation with GM
      CSF and M-CSF did not inhibit macrophage colony formation. CONCLUSIONS: GM-CSF
      can possibly influence the proliferative response induced by M-CSF. Nonadherent
      macrophage precursors recovered from different tissue compartments seem to differ
      in their sensitivity to growth regulation.

PMID- 8988405
TI  - Perspectives on immunotoxicity regulatory guidelines.
AB  - The regulatory guidelines relating to testing for immunotoxicity are not
      harmonised amongst the various agencies. This paper outlines the current
      situation within Europe, Japan and the USA. The agencies within the USA
      representing both agrochemicals and food additives are the most demanding in
      their requirements, and these guidelines are currently used as the definitive
      requirements for the testing of compounds for immunotoxicity.

PMID- 8988406
TI  - Pathology of toxic effects on the immune system.
AB  - The lymphoid organs/tissues are widely distributed throughout the body. However,
      a study of the primary and secondary lymphoid organs provides an adequate
      assessment of immune status. A histopathological approach to investigate
      immunotoxicity of various agents is described. The advantages and limitations of
      this approach are discussed. The usefulness of immunocytochemistry as an aid to
      study the various sub-populations of lymphocytes are stressed. Histopathological
      assessments are useful in evaluating immunosuppressive responses. Their value is
      somewhat less obvious in studying the potentials of test compounds for allergic
      and hypersensitive reactions. Variable factors affecting the structure and
      function of lymphoid organs such as stress, nutrition and age are discussed.
      Pathological lesions produced by various agents in lymphoid organs such as
      thymus, bone marrow, spleen, and lymph nodes are described.

PMID- 8988407
TI  - T cell reactions in patients showing adverse immune reactions to drugs.
AB  - OBJECTIVE AND DESIGN: To better understand how T cells react to small compounds,
      we investigated the in vitro T cell reactivity to drugs from drug allergic
      patients. MATERIAL AND SUBJECTS: Peripheral blood mononuclear cells (PBMC) of
      three drug allergic individuals were stimulated in vitro by different drugs.
      METHODS: Proliferation was assayed by 3H-thymidine incorporation. Upregulation of
      activation parameter on T cells was done by immunofluorescence and cytokine
      release determined via standard ELISA. RESULTS: Drugs can stimulate both CD4 and
      CD8 T-cell subsets. PenG-stimulated PBMC showed a heterogenous cytokine pattern
      and clones secreted high amounts of INF gamma. In contrast, sulfamethoxazole and
      lidocaine-stimulated PBMC secreted high levels of IL-5 and lidocaine-specific
      clones can be Th1 or Th2-like. CONCLUSION: Drug specific T cells play a pivotal
      role in drug hypersensitivity reactions, both by regulating the immune response
      and probably also as specific effector cells with different patterns of cytokine
      release.

PMID- 8988408
TI  - The popliteal lymph node assay in mice: screening of drugs and other chemicals
      for immunotoxic hazard.
AB  - The popliteal lymph node assay (PLNA) in mice represents a predictive test for
      assessing the sensitizing (allergenic and autoimmunogenic) potential of drugs and
      low molecular weight chemicals. Measuring activation of the draining lymph node
      of the hind paw, the PLNA facilitates the detection and analysis of immunotoxic
      effects in a rapid and reproducible manner. An attractive feature of the PLNA is
      that it can be performed in combination with the routine toxicity testing
      required for new drugs. Thus, it is possible to investigate whether animals
      exposed by the oral, intravenous, or inhalative route have been sensitized to the
      test compound or a reactive metabolite of the test compound generated in vivo.
      PLNAs may be appropriate supplements to routine toxicity screening of chemicals,
      thereby enhancing chemical safety.

PMID- 8988409
TI  - Clinical immunotoxicity of antirheumatic drugs.
AB  - Non-steroidal antiinflammatory drugs (NSAIDs), corticosteroids and disease
      modifying antirheumatic drugs are commonly used for the treatment of the
      inflammatory rheumatic diseases. In addition to their antiinflammatory effects,
      many of these drugs influence an otherwise impaired immune system, which may
      result clinically in decreased resistance to infection and/or increased incidence
      of malignancies, in stimulation of the immune response and autoimmune diseases,
      or in allergy or hypersensitivity. Only corticosteroids increase considerably the
      risk of infections, immunosuppressive agents-at the low doses used in
      rheumatology-do not have this effect. Although the data are conflicting,
      neoplasms, especially leukaemias and lymphomas seem to develop more frequently
      during immunosuppressive treatment. Methotrexate, most commonly used nowadays in
      the early stage of joint disease, does not seem to increase the risk of
      malignancies. Although several drugs may induce autoimmune diseases, d
      penicillamine is the commonest inducer. NSAIDs have the greatest propensity to
      produce allergy or hypersensitivity, causing various cutaneous, renal, and
      bronchial symptoms, and rarely vasculitis. Methods for the measurement of their
      plasma concentrations are available for most of the drugs, although not routinely
      used. Clinical vigilance, regular check-ups and full knowledge of side effects
      are crucial in the diagnosis of drug-induced immunotoxicity, especially because
      the symptoms and signs of immunotoxicity may mimic the naturally occurring
      features of the underlying disease.

PMID- 8988410
TI  - [Pharmacokinetic and clinical evaluation of azithromycin using fine granules or
      capsules in the pediatric patients].
AB  - Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules
      was studied for pharmacokinetic and clinical evaluations. 1. Antibacterial
      activities. MIC profile of AZM was as follows: 0.78 approximately 1.56
      micrograms/ml against Staphylococcus aureus, < or = 0.025 approximately 0.10
      microgram/ml against Streptococcus pyogenes, 0.10 approximately 0.39 and 6.25
      micrograms/ml against Streptococcus pneumoniae, < or = 0.025 approximately 0.39
      microgram/ml against Moraxella(Branhamella) catarrhalis, 0.39 approximately 3.13
      micrograms/ml against Haemophilus influenzae, and 0.20 approximately 6.25
      micrograms/ml against Haemophilus parainfluenzae. 2. Absorption and excretion.
      The elimination half-life of AZM after its administration at 10 mg/kg/day for
      three days was 28.1 approximately 46.1 hours. The cumulative urinary excretion
      rate in the first 120 hours after start of treatment was 4.01 approximately
      8.47%. 3. Clinical evaluation. AZM was given to 76 pediatric patients to treat
      following infections: pharyngitis in seven, tonsillitis in 11, bronchitis in 11,
      pneumonia in 19, Mycoplasma pneumonia in eight, scarlet fever in 13, infective
      enteritis in one, SSTI in four, and otitis media in two. Effectiveness of AZM was
      assessed in 75 patients and the drug was rated "excellent" or "good" in 71
      resulting in an efficacy rate of 94.7%, 87.0% of the 46 cases indicated that AZM
      had eradicated bacteria identified before the treatment. One patient complained
      of moderate diarrhea which disappeared after treatment of anti-diarrheic.
      Abnormal laboratory changes were reported in 12 patients in the following:
      decreased leukocytes in eight, increased eosinophils in two, increased platelet
      count in one, and increased GPT in one. All cases of abnormality was deemed mild
      in severity and clinically insignificant.

PMID- 8988411
TI  - [Pharmacokinetic and clinical evaluation of azithromycin in pediatrics].
AB  - Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules
      was administered at a standard dose of 10 mg/kg once daily for 3 days to
      pediatric patients with bacterial infections. AZM was studied for its
      pharmacokinetic and clinical evaluation. 1. AZM possessed potent activity against
      Gram-positive bacteria and Gram-negative bacteria that had been clinically
      isolated. 2. Plasma samples were collected from two patients diagnosed as having
      pneumonia or enteritis, and urine samples were collected from one patient
      diagnosed as having pneumonia for drug level determination. The drug
      concentrations in plasma were 0.095 and 0.204 microgram/ml just before the end of
      treatment, and 0.017 and 0.096 microgram/ml at 48 hours post-treatment. The drug
      concentrations in urine were 5.16 micrograms/ml and 5.63 micrograms/ml during a
      period between 24 and 48 hours and between 48 and 72 hours after the start of
      treatment, respectively. 3. The drug was found effective in 37 of 38 cases with
      various pediatric infections. AZM treatment eradicated bacteria in 17 of 30
      strains (56.7%). 4. One patient complained of mild vomiting, while abnormal
      laboratory test results indicating mild eosinophilia were reported in four cases.

PMID- 8988412
TI  - [Clinical study of a macrolide antibiotic, azithromycin, in pediatric patients].
AB  - Azithromycin (AZM), 10% fine granules or 100 mg capsules, were given orally to 27
      children with various pediatric infections. The results of the study are shown
      below. 1. Pharmacokinetic investigation. We studied plasma and urinary
      concentrations after 100 mg AZM capsules were given. One patient received 8.3
      mg/kg of AZM once a day for 3 days, and AZM concentration in plasma was 0.033
      microgram/ml 48 hours after the final dosing. Doses of 8.3 and 12.5 mg/kg body
      weight of AZM were respectively given to two patients once daily for 3 days. As a
      result, AZM concentrations in urine during a period between 96 and 120 hours post
      dosing were 1.67 and 4.53 micrograms/ml, respectively, and urinary excretion rate
      in 120 hours after the first dosing was 10.54% in the patient that was given 12.5
      mg/kg. 2. Clinical investigation. Clinical efficacies were examined in 24
      patients. Excellent results were obtained in 7 patients, good results in 14
      patients, hence the clinical efficacy rate was 87.5%. Bacteriologically,
      Haemophilus influenzae strains isolates from 2 patients were eradicated in 1 and
      decreased in the other. Safety was evaluated in 26 patients. An adverse reaction
      was observed in 1 patient (urticaria). Abnormal laboratory test results were
      observed in 2 patients, decreased WBC in 1 and elevation of eosinophils in the
      other. The above results suggest that AZM is a useful oral antibiotic for
      pediatric patients with infection with susceptible organisms.

PMID- 8988413
TI  - [A clinical evaluation of azithromycin in the treatment of pediatric infection].
AB  - Fine granule preparation of azithromycin (AZM), a new macrolide antibiotic, was
      given to treat various infections in pediatric patients. Efficacies of AZM in a
      total of 21 patients (tonsillitis in six, bronchitis in five, pneumonia in five,
      impetigo contagiosa in three, staphylococcal scalded skin syndrome in one and
      bacterial enterogastritis in one) were rated "excellent" in 11 patients and
      "good" in eight. The remaining two cases were not included in the evaluation. AZM
      eradicated all strains of infection-causative bacteria identified in the 21
      patients: Staphylococcus aureus in two, Streptococcus pneumoniae in four,
      Moraxella (Branhamella) catarrhalis in four, Haemophilus influenzae in six,
      Haemophilus parainfluenzae in three and Mycoplasma pneumoniae in one. One patient
      complained of mild diarrhea, while two patients showed increases in eosinophils
      as abnormal laboratory changes.

PMID- 8988414
TI  - [Pharmacokinetic and clinical evaluations of azithromycin in the pediatric
      field].
AB  - Azithromycin (AZM), an oral macrolide antibiotic drug, was studied for its
      efficacy and pharmacokinetics in the treatment of pediatric patients with
      respiratory tract infections. The results of the study are presented. Fifteen
      pediatric patients in an age range between 1 and 10 years were given 8.9 to 14.7
      mg/ kg body weight of AZM once daily for 3 to 4 days. Pharmacokinetics of AZM in
      three patients were examined. AZM concentration in plasma was 0.037 microgram/ml
      at 72 hours after final dosing, while urine concentration was 10.9 micrograms/ml
      measured during a period between 72 and 96 hours post-dosing. Fourteen patient
      cases were included in analysis of drug efficacy for AZM. AZM was found "markedly
      effective" in all seven patients with pneumonia, and "effective" in all three
      patients with acute bronchitis, two patients with mycoplasmal pneumonia, and one
      patient with tonsillitis. In one patient with mycoplasmal bronchitis, AZM was
      found slightly effective. The efficacy rate was 92.9% (13/14). The study found
      one case of side effect, moderate diarrhea. No laboratory abnormality was
      documented. In conclusion, an antibiotic AZM was found useful in a treatment of
      pediatric respiratory tract infections.

PMID- 8988415
TI  - [Pharmacokinetic and clinical evaluation of azithromycin in pediatric
      infections].
AB  - Azithromycin (AZM) was studied for its concentrations in plasma and urine,
      efficacy and safety. 1. Plasma and urine samples were collected from one patient
      diagnosed as having Mycoplasma pneumonia for drug level determination. The drug
      was given once daily at 9.7 mg/kg body weight for three days. The drug
      concentrations in plasma was 0.149 microgram/ml in 12 hours after the start of
      the treatment, and 0.095 microgram/ml at the point of 24 hours after the end of
      the treatment. Urinary recovery rate up to 72 hours post-dosing was 6.39%. 2. The
      effectiveness of AZM was assessed in 19 patients with following diagnoses:
      pharyngitis in two patients, bronchitis in four, pneumonia in seven and
      Mycoplasma pneumonia in six. The drug was rated "excellent" in 11, "good" in
      seven, "poor" in one, resulting in an efficacy rate of 94.7%. 3. AZM eradicated
      two strains of Streptococcus pyogenes and Streptococcus pneumoniae identified in
      patients. 4. The AZM MIC's were 0.39 microgram/ml against Staphylococcus aureus,
      0.20 microgram/ml against S. pneumoniae, < or = 0.0008 microgram/ml against
      Mycoplasma pneumoniae. 5. One patient complained of mild diarrhea, while another
      showed a slight increase in eosinophils, suggesting an abnormal laboratory
      change. In conclusion, AZM was found useful in treatment of pediatric infections.

PMID- 8988416
TI  - [Pharmacokinetic and clinical studies on azithromycin in children].
AB  - Azithromycin (AZM) is a new oral macrolide antibiotic drug. AZM either in 10%
      fine granules form or in 100 mg capsule form was studied for its pharmacokinetics
      and treatment efficacy in pediatric patients with various infections. 1.
      Pharmacokinetics. Plasma and urine samples were collected from four patients with
      pharyngitis and post-dosing drug levels were determined. The drug was given once
      daily at 10 mg/kg body weight for 3 days. The drug concentrations found in plasma
      at 96 hours after the first dosing (48 hours after the final dosing) lay in a
      range of 0.02 and 0.04 microgram/ml and in urine at 120 hours after the first
      dosing (72 hours after the final dosing) in a range between 3.2 and 7.7
      micrograms/ml. AZM was found in two patients but no effect was observed on blood
      levels of theophylline determined between 48 and 96 hours after the first dosing
      in the treatment of underlying bronchial asthma. 2. Clinical study results.
      Clinical studies of AZM was carried out in 25 pediatric patients with bacterial
      infections that mainly affected the respiratory tract. The patients received
      either 10% fine granules at 10 or 20 mg/ kg body weight or 100 mg capsules at 10
      mg/kg body weight once daily over 3 to 6 days. The drug was found markedly
      effective in six patients, moderately effective in thirteen patients, while the
      investigators could not assess the drug efficacy in six patients. Although no
      side effect was reported in the study, two patients experienced slight decrease
      in WBC.

PMID- 8988417
TI  - Bovine and porcine trabecular cells produce prostaglandin F2 alpha in response to
      cyclic mechanical stretching.
AB  - Bovine and porcine trabecular cells in Petri dish cultures were exposed to cyclic
      mechanical stretching of the dish bottom for 30 second cycles (2 Hertz) at a
      strain magnitude of 4.5 mm/m for up to 3 days. Growth rate of the cells was not
      affected by the stretching but production of prostaglandin F2 alpha (PGF2 alpha)
      increased. We believe one stimulus for production of PGF2 alpha in trabecular
      cells may be the stretching of the trabecular meshwork caused by changes in
      aqueous flow and intraocular pressure.

PMID- 8988418
TI  - Vitreous changes during ocular inflammation induced by interleukin 1 beta.
AB  - To determine the mechanisms of vitreous changes during ocular inflammation, we
      investigated these changes, focusing on the collagen, in an experimental model of
      ocular inflammation induced by intravitreal injection of interleukin 1 beta in
      rabbits. Inflammation caused gel contraction, with release of a watery liquid
      from the gel, and increases in the amount of insoluble material and high
      molecular-weight components of the vitreous collagen, presumably due to extensive
      cross-links of the collagen molecules. The cross-links of vitreous collagen may
      promote vitreous gel contraction and the release of watery liquid from the gel.

PMID- 8988419
TI  - Collagen types in healing alkali-burned corneal stroma in rabbits.
AB  - We evaluated the change in the type of collagen found during healing in the
      alkali-burned corneal stroma of rabbits. We estimated the relative proportions of
      alpha chains in pepsin-solubilized collagen, using sodium dodecylsulfate
      polyacrylamide gel electrophoresis. Bands of alpha 1(I), alpha 2(I), alpha 1(V),
      and alpha 1(III) chains stained with Coomassie Blue were separated. The alpha
      1(III) and alpha 1(V) chains showed a transient proportional increase in healing
      corneal stroma in the area exposed to alkali. No significant alterations in
      collagen alpha chains were detected in peripheral corneal stroma that had not
      been directly exposed to alkali. Our results suggest that the keratocytes which
      repopulate the alkali-injured corneal stroma early in healing synthesize a higher
      proportion of collagen types III and V than type I, and then switch to
      synthesizing predominantly type I collagen as stromal healing progresses.
      Collagen types III and V thus appear to be of primary importance in the healing
      of the corneal stroma.

PMID- 8988420
TI  - Fluorophotometry with a small animal adapter.
AB  - The usefulness of the Fluorotron Master fluorophotometer fitted with a small
      animal adapter was evaluated with tree shrews. We also determined that the
      optimal measurement parameters for these animals, which are regarded as promising
      for experimental use in ophthalmic research, are: fluorescein-Na concentration,
      0.5 x 10(-9) to 1.0 x 10(-6) g/mL; fluorescein-Na dosage, 2 mg/kg; measurement
      time, 30 minutes after injection of fluorescein-Na into the ocular compartments.
      Results indicated that ultrafiltration for the measurement of protein-unbound
      fluorescein can be done with a hematocrit tube and a minimal blood sample,
      thereby reducing the impact of the sampling on the animal's general condition.
      The Fluorotron Master with the small animal adapter can offer advantages in
      estimating the blood-ocular barrier permeability using disease models in tree
      shrews.

PMID- 8988421
TI  - Retinopathy in diabetic (KKA gamma) mice: diabetic microvascular changes to the
      retina in KKA gamma mice revealed by light and electron microscopy.
AB  - Pericytic changes in the retinal vessels of diabetic (KKA gamma) and control
      (C57BL) mice were studied by light and electron microscopy. An improved
      histochemical technique for alkaline phosphatase was used in the light
      microscopic study. In the control mice, a continuous pathway was identified
      extending from the retinal arterioles, via the superficial and deep retinal
      capillaries, to the retinal venules. The deep retinal capillaries formed networks
      and were localized within the deeper retinal layers; the retinal arterioles,
      superficial capillaries, and venules were present in the nerve fiber layer.
      Examination of KKA gamma mice, aged 16 to 28 weeks, revealed engorgement of the
      arterioles, hypertrophy of the pericytes (which contained numerous actin
      filaments) within the superficial retinal capillaries, and narrowing of the deep
      retinal capillaries. These microvascular changes indicate retinal hyperperfusion,
      local hypertension of the superficial retinal capillaries, adaptive
      hyperfunctional changes in the pericytes of these capillaries, and ischemia of
      the deep retinal capillaries. The pericytic changes observed in the diabetic
      capillaries contrasted sharply with previous reports; an explanation for this
      variance is suggested.

PMID- 8988423
TI  - Measurement of optic nerve head circulation: comparison of laser speckle and
      hydrogen clearance methods.
AB  - Microcirculation in the optic nerve head (ONH) in the ocular fundus was measured
      noninvasively using the recently developed laser speckle circulation analyzer.
      Results were compared with capillary blood flow (CBF) measurements made by the
      hydrogen clearance method. The ONH blood flow of six normal rabbits was measured
      simultaneously by both methods. Inhalation of 10% carbon dioxide (CO2) increased
      the CBF by 22% (hydrogen clearance method). Intravenous injection of endothelin-1
      (ET-1) (10(-10) mol/kg) decreased the CBF by 19%. Significant correlations were
      found between the NB (normalized blur) value by the laser speckle method and CBF
      (r = 0.38, P < 0.05, n = 30) and also between the relative change of NB and CBF
      (r = 0.92, P < 0.01, n = 30) in the ONH. This indicates that evaluation of the NB
      change in the ONH is as accurate with the laser speckle method as with the
      hydrogen clearance method, giving a basis for the clinical application of the
      laser speckle method of measuring ONH circulation.

PMID- 8988422
TI  - FGF receptor 1 expression in experimental choroidal neovascularization.
AB  - Fibroblast growth factor (FGF) is an important factor in neovascularization. To
      clarify the role of FGF, we demonstrated the expression of FGF receptor 1 mRNA in
      experimentally induced choroidal neovascularization using in situ hybridization.
      Krypton laser photocoagulation was applied to the posterior retina of colored
      rats to induce choroidal neovascularization; the eyes were removed at various
      intervals after photocoagulation. Chorioretinal sections were made, and FGF
      receptor 1 cDNA fragments were used to make antisense and sense probes for in
      situ hybridization. In normal chorioretinal tissue, stain indicating FGF receptor
      1 mRNA was observed in the ganglion cells and the inner nuclear layer. After
      photocoagulation, FGF receptor 1 mRNA appeared in the retinal pigment epithelial
      cells, in melanocytes of the choroid and in the choroidal blood vessel wall of
      the photocoagulation lesions. This suggests that FGF is involved in the process
      of neovascularization. Previous studies have reported that the capillary
      endothelial cells and retinal pigment epithelial cells produce basic FGF in
      vitro; FGF may affect the cells in an autocrine or paracrine manner.

PMID- 8988424
TI  - A new method to selectively injure the optic nerve using argon-laser
      photocoagulation.
AB  - To create a model by noninvasive means for the study of Wallerian and
      transneuronal degeneration of the central nervous system, we devised a two-step
      argon laser photocoagulation (ALP) procedure with which we could selectively
      injure the optic nerve in rats. Changes in the optic nerve distal to the site of
      injury were studied histologically to evaluate this method; we succeeded in
      selectively and completely injuring the optic nerve. We found this ALP technique
      to be superior to either the panretinal or one-step photocoagulation method.
      Changes within astrocytes of the intracerebral optic tract and the lateral
      geniculate body in animals were also studied immunohistochemically following ALP
      and compared with those which follow enucleation. Reactive astrocytes with
      enhanced immunoreactivity for glial fibrillary acidic protein (GFAP) increased in
      number in the intracerebral optic tract and in the lateral geniculate body on the
      contralateral side of the optic injury in both groups of animals. The increased
      GFAP immunoreactivity was sustained for 6 weeks following injury; the
      proliferative tendency of the glial cells, shown by the bromodeoxyuridine method,
      peaked 3 days after injury and then decreased gradually. These glial responses in
      the optic tract and lateral geniculate body of animals subjected to ALP are
      similar to those of animals following enucleation. Our results indicate that this
      new technique for selectively and noninvasively injuring the optic nerve with ALP
      is applicable to the study of Wallerian and transneuronal degeneration.

PMID- 8988425
TI  - Apoptosis regulated by growth factors in multicellular spheroids of trabecular
      cells.
AB  - Bovine and porcine trabecular cells were incubated up to one month in a
      polystyrene dish nonadherent environment for suspension culture, and their
      morphological changes were examined by light and electron microscopy. The
      trabecular cells formed multicellular spheroids during the first day. Apoptosis
      occurred selectively and continuously in the spheroids, which had initially been
      filled with cells. After one month, the final structure of the spheroids had
      become a meshwork of cells separated by large extracellular spaces. Epidermal and
      basic fibroblast growth factors prevented apoptosis of the trabecular cells in
      the spheroids which remained filled with cells for the entire observation period.
      The trabecular multicellular spheroids may represent the in vivo process of
      trabecular meshwork formation and can be used as a system for identifying
      regulatory factors involved in this process.

PMID- 8988426
TI  - Susceptibility of cultured rabbit corneal epithelial cells to various herpes
      simplex virus isolates.
AB  - Rabbit corneal epithelial cells were cultured in rabbit corneal epithelial growth
      medium containing 0.03 mM/L Ca2+ without serum. Their susceptibility to herpes
      simplex virus (HSV) was compared with that of vero cells. Six clinical isolates
      obtained from the cornea, three from the oral mucosa, and two from the facial
      skin were examined. The 50% tissue culture infectious dose (TCID)50 of each
      isolated strain was calculated for both types of cells. Corneal epithelial cells
      appeared to be more susceptible to all strains isolated from the cornea or oral
      mucosa, while corneal epithelial cells and vero cells appeared to be equally
      susceptible to the two isolates from the skin. Thus, isolates derived from
      herpetic keratitis will grow better in corneal epithelial cells, suggesting that
      rabbit corneal epithelial cells are more suitable for isolating viruses from the
      cornea.

PMID- 8988428
TI  - Atheromatous and atheroma-like lesions of the central retinal artery:
      histopathological correlations.
AB  - Arteriosclerosis is very rare in the distal central retinal artery (CRA) of aged
      eyes devoid of significant ocular pathology. Nevertheless, atheromatous and
      atheroma-like lesions are occasionally observed in routine ophthalmic pathology.
      We investigated the histopathologic correlations of the eyes and vessels
      involved. Twenty-eight globes presenting atheromatous and atheroma-like lesions
      (defined as accumulations of foamy macrophages in the tunica intima) in the CRA
      or its first-order branches were obtained from our files and studied under light
      microscopy. Vessels were examined for 7 histological characteristics related to
      atherogenesis, and the histopathological features of the involved eyes were
      analysed. Deposits of foamy macrophages were observed most frequently in the
      postlaminar CRA, followed by the intraneural and the intralaminar segment. There
      was a conspicuous association with glaucoma (78.6%), especially neovascular
      glaucoma (71.4%). The most frequently associated ocular pathologic features were
      optic atrophy (96.4%), atrophy of the inner retina (85.7%), cataract (64.3%), and
      inflammatory conditions (50%). Atheromatous and atheroma-like lesions of the CRA
      appear to be more common than generally reported. It is unlikely that they
      represent an age-related degenerative type of arteriosclerosis. They are more
      likely to be primarily or secondarily related to the severe ocular disease
      conditions with which they are found.

PMID- 8988427
TI  - Implications of the severity of retinopathy of prematurity on childhood
      development.
AB  - This study investigated the severity of retinopathy of prematurity (ROP) and its
      relationship to childhood development. The subjects were 21 children with a
      birthweight of 2500 g or less who were tested for flash visual evoked potential
      (FVEP) at conceptual ages ranging from 1 to 3 years. We also examined 73 children
      with a birthweight of 1500 g or less, using the Developmental Quotient (DQ) test,
      at 2 1/2 years of age. Twenty-five of this group were given an Intelligence
      Quotient (IQ) test at 6 to 7 years of age. The P100 latency of FVEP in the severe
      ROP group was significantly longer than that of the mild ROP group (P < 0.05).
      The main DQ in the severe ROP group was 99.1 +/- 17.9, significantly lower than
      the 108.7 +/- 15.5 of the mild ROP group (P < 0.05). No significant IQ
      differences were found between the two groups. The proportion of children with
      verbal-performance IQ discrepancies was, however, significantly greater in the
      severe ROP group than in the mild ROP group (P < 0.05). Since infants with severe
      ROP are more likely to suffer developmental disorders, long-term follow-up is
      absolutely necessary and must be done in cooperation with pediatricians.

PMID- 8988429
TI  - Ophthalmic tumor formation in Waldenstrom's macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia is a malignant disease of the reticuloendothelial
      system; ocular complications reported previously have been concerned chiefly with
      hyperviscosity manifestations. Ophthalmic tumor formation is rare, although not
      unheard of, in this particular condition. This report describes two rare
      instances of Waldenstrom's macroglobulinemia which involved conjunctival and
      orbital tumors. One patient developed the tumors after a lengthy clinical course;
      in the other patient, eyelid and orbital tumors were the first symptoms. Careful
      examination of the external eye, especially the fornix of the conjunctiva, in
      patients with Waldenstrom's macroglobulinemia can identify an initial lesion or
      invasions to other organs.

PMID- 8988430
TI  - Detection of herpes simplex virus DNA in tear fluid of stromal herpetic keratitis
      patients by nested polymerase chain reaction.
AB  - The value of the polymerase chain reaction (PCR) in the diagnosis of stromal
      herpetic keratitis was examined using tear fluid specimens; the sensitivity of
      the nested PCR method in detecting the herpes simplex virus (HSV) genome was 1
      plaque-forming unit/mL. PCR assay of 72 tear samples from the eyes of 15 patients
      with stromal herpetic keratitis detected the HSV genome in 5 (33.3%). No positive
      band was detected in 20 tear samples from both eyes of 10 healthy volunteers.
      Seven of 38 tear samples (18.4%) and 1 of 34 samples (2.9%) collected from the
      diseased eye and the contralateral normal eye, respectively, produced positive
      results; the difference in rates was statistically significant (P < 0.05). The
      positive rate of samples collected from the diseased eye during an active phase
      was 16.0% (4 of 25 samples); in the quiescent phase, 23.1% (3 of 13 samples); the
      difference was not significant (P = 0.45). In HSV genome-positive cases, the
      average number of tear collections needed to detect the HSV genome was 3.3.
      Results indicate that PCR assay of tear fluid provides valuable information for
      the diagnosis of stromal herpetic keratitis, and that repeated tear samples
      should be collected regardless of the phase of the phase of disease activity.

PMID- 8988431
TI  - Optic sharp edge or convexity: comparison of effects on posterior capsular
      opacification.
AB  - Posterior capsular opacification was evaluated in 46 eyes with an implanted sharp
      edged biconvex (BC) lens, 108 eyes with the sharp-edged convex-plano (CP) lens,
      160 eyes with the round-edged BC lens and 58 eyes with the round-edged CP lens.
      In each eye, the intraocular lens had been fixed in the sac after continuous
      circular capsulorrhexis, with the optic edge completely enclosed by the anterior
      capsule. Two years postoperatively, the posterior capsules of these eyes were
      photographed and the degree of opacification was classified as Grade 1 (clear) to
      Grade 4 (severely opacified). In the sharp-edged BC group, 91% of the eyes were
      Grade 1; 4% Grade 2; 2% Grade 3; 2% Grade 4. In the sharp-edged CP group, the
      corresponding percentages were 83, 7, 4, and 6; for the round-edged BC group: 18,
      27, 24, and 31; and for the round-edged CP group: 34, 17, 28, and 21. These
      findings suggest that the most significant factor in prevention of posterior
      capsular opacification is the sharpness of the optic edge. We believe that the
      sharp optic edge creates higher pressure on the posterior capsule and acts as a
      barrier to lens epithelial cell migration.

PMID- 8988432
TI  - Structure and magnetic resonance imaging of the fiber connection between
      Whitnall's ligament and the superior wall of the orbit.
AB  - To confirm the structure of the fiber connection between Whitnall's ligament and
      the superior wall of the orbit, ten orbits from five Japanese cadavers were
      examined by magnetic resonance imaging (MRI) and dissection. MRI showed a well
      circumscribed low-intensity signal at the fiber connection. Pre-aponeurotic fat
      was prominent and the fibers originating from Whitnall's ligament were fused at
      the lower face of the capsule of the pre-aponeurotic fat in four cadavers. Fibers
      originating from the upper face of the fat were attached to the superior
      periorbit (minimum width: 15 mm). The fifth cadaver had very little pre
      aponeurotic fat and few fibers. These anatomic differences may be within the
      normal range of variation. The fibers may support Whitnall's ligament and may
      help to retract pre-aponeurotic fat during levator muscle contraction as the eye
      opens.

PMID- 8988434
TI  - Current trends in cataract and refractive surgery in Japan--1995 survey.
AB  - A fourth annual survey was carried out by mail in February 1996 to investigate
      the current trends in cataract and refractive surgery in Japan. A questionnaire
      was sent to 911 ophthalmologist members of the Japanese Society of Cataract and
      Refractive Surgery. Data received from 46.7% of the recipients were cross
      analyzed and compared with those from the previous surveys.

PMID- 8988433
TI  - Progressive zonal outer retinitis.
AB  - A 27-year-old woman with uniocular progressive zonal outer retinitis was
      examined. The retinitis area was curvilinear and gray, with zonal opacification.
      It enlarged centrifugally and concentrically, with narrowing of the zonal
      opacification. Results of perimetry and electroretinography showed that the outer
      retina was primarily affected. Damage was more severe in the photoreceptor cones
      than in the rods. Peripheral retinal phlebitis was seen on fluorescein
      angiography. Intraretinal pigment migration with retinal pigment epithelial
      atrophy occurred in the macula as sequelae.

PMID- 8988435
TI  - Effect of vitrectomy on epiretinal membranes after endogenous fungal
      endophthalmitis.
AB  - Pars plana vitrectomy was used to remove proliferative membranes caused by
      endogenous fungal endophthalmitis in 3 patients (3 eyes). Tractional retinal
      detachment was present in all. In 2 eyes, a fibrovascular membrane originated in
      the optic nerve head and was connected to a full-thickness chorioretinal scar. In
      the other, a thick preretinal membrane was found in the macula, with total
      retinal detachment. In all eyes, the epiretinal membrane was successfully removed
      and the retina reattached. Visual outcome depended on the site of the
      chorioretinal scar. We advocate pars plana vitrectomy as the method of choice for
      tractional retinal detachment following fungal endophthalmitis.

PMID- 8988436
TI  - Volume measurement of horizontal extraocular muscles with magnetic resonance
      imaging.
AB  - The horizontal extraocular muscle volume of 11 normal adults and 3
      ophthalmoplegic patients was measured with magnetic resonance imaging (MRI),
      using a 1.5 Tesla superconductive system which can provide T1 weighted images of
      3 mm gapless slices of the orbit with the spin echo technique. The MRI film was
      projected and magnified on Kent paper with an overhead projector; muscle shapes
      were traced and cut from the paper. Muscle volume was defined as the total weight
      of the Kent paper shapes representing the muscles from all MRI slices. The
      average volumes of the medial and lateral rectus muscles (MRM, LRM) of the 11
      subjects were 690 +/- 87 mm3 and 734 +/- 77 mm3. In two patients with peripheral
      nerve palsy, the small muscle volume was classified as atrophic; in the one
      patient with orbital myositis, the large muscle volume was classified as
      hypertrophic. This measurement technique is useful for evaluation of the
      extraocular muscles, especially in ophthalmoplegia.

PMID- 8988437
TI  - Wound infection after cataract surgery.
AB  - Nineteen patients were treated for bacterial and fungal infection of the
      sclerocorneal incision following cataract extraction during a 19-year period. The
      infections were caused by Staphylococcus aureus (2), Staphylococcus epidermis
      (2), Streptococcus pneumoniae (3), Streptococcus viridans (1), Pseudomonas
      aeruginosa (1), Mycobacterium fortuitum (3), Aspergillus flavus (6), and Candida
      tropicalis (1). The predisposing factors involved were an obstructed nasolacrimal
      duct (S. pneumoniae, S. viridans), airborne contamination of the wound by fungal
      spores (A. flavus), and defective sterilization of instruments (M. fortuitum).
      Ten of the 19 infections resulted in complete loss of the eye from
      endophthalmitis. Early recognition of wound infection by frequent meticulous
      examination of the sclerocorneal incision for infectious infiltration is of
      utmost importance so that specific therapy can be instituted immediately to
      prevent the development of endophthalmitis.

PMID- 8988438
TI  - Modifications of arterial baroreflexes: obligatory roles in cardiovascular
      regulation in stress and poststress recovery.
AB  - Despite the physiological importance of arterial baroreflexes as a powerful
      stabilizer of blood pressure, their functions themselves are not always stable
      and there are a variety of circumstances in which they are significantly
      modulated. During stressful conditions, including fight/flight, defense/attack,
      somatic nociception, visceral nociception, exercise, and mental stress, arterial
      baroreflexes are generally inhibited. The inhibition is purposeful for achieving
      dynamic readjustment of circulation needed for the animal's reaction to cope with
      these conditions. Central sites which are proposed to be involved in the
      inhibition include the motor cortex, amygdala, hypothalamus, dorsolateral part of
      the periaqueductal gray matter, parabrachial nucleus, cerebellar vermis, etc. On
      the other hand, arterial baroreflexes are occasionally facilitated, during sleep,
      following endurance exercise, etc. The facilitation favors restoration of energy
      exhausted during a stressful phase in which the animal reacts actively to
      changing environment. The central sites proven to elicit the facilitation are the
      medial prefrontal cortex, the preoptic/anterior hypothalamus, the ventrolateral
      part of the periaqueductal gray matter, and the nucleus raphe magnus. The
      inhibition and facilitation of arterial baroreflexes, which probably occur
      alternatively, are essential mechanisms supporting reactions to stressful
      conditions and poststress recovery, respectively. This review describes when,
      how, and why the arterial baroreflexes are so modulated.

PMID- 8988439
TI  - Cellular approach to auditory signal transmission.
AB  - The aim of this article is to review the findings of current research on the
      synaptic transmission of the auditory afferent tract from hair cells to brain
      stem auditory nuclei. The depolarization of inner hair cells by the activation of
      mechano-electrical transduction channels induces the entry of Ca ions through the
      voltage-gated Ca2+ channel. This Ca2+ influx triggers the transmitter release.
      The transmitter is likely glutamate, and it generates EPSPs at the afferent
      terminal and elicits action potentials. The intensity and the temporal
      information of sounds are processed separately by specific auditory tracts and
      coded as frequency-selective and phase-locked behaviors of action potentials.
      Recent studies using the whole-cell patch-clamp technique revealed several
      voltage-gated and chemically gated ion channels; these channels characterize the
      intensity coding and the time-coding functions of auditory neurons.

PMID- 8988440
TI  - Endogenous arachidonic acid inhibits hypotonically-activated Cl- channels in
      isolated rat hepatocytes.
AB  - Properties of hypotonically-activated Cl- channels in isolated rat hepatocytes
      were studied by the patch-clamp whole-cell technique. Hypotonic stress (140-150
      mosmol kg 1 H2O) induced a hyperpolarization of the membrane of hepatocytes in
      the presence of an inwardly oriented Cl gradient, but had no effect on the
      membrane potential in the absence of Cl. An increase in the hypotonically-induced
      conductance was significantly inhibited by 4-acetamido-4'-isothiocyanatostilbene
      2, 2'-disulfonic acid (SITS; 50 microM), but not by Ba2+ (1 mM). Pre-incubation
      with arachidonic acid (20 microM) significantly inhibited the hypotonically
      activated conductance. The combined application of a cyclo-oxygenase inhibitor,
      indomethacin (50 microM) and a lipoxygenase inhibitor, esculetin (100 microM)
      also inhibited the conductance, whereas quinacrine (200 microM), a phospholipase
      A2 inhibitor, significantly induced a large steady conductance. Outward Cl-
      currents, but not cationic currents, were elicited by the hypotonic stress. The
      current did not show any rapid time-dependent inactivation during the voltage
      clamp of 0.1 s. The combined application of arachidonic acid, indomethacin and
      esculetin inhibited the hypotonically-activated Cl- currents. The present study
      has shown that the Cl- channel is activated by exposure to hypotonic stress and
      closed by an increase in arachidonic acid concentration in isolated rat
      hepatocytes.

PMID- 8988441
TI  - Tracheal, circulatory, and respiratory responses to femoral nerve stimulation.
AB  - Tracheal, circulatory, and respiratory responses to electrical stimulation of the
      afferent nerve from the hindlimb were analyzed in decerebrate, paralyzed, and
      mechanically ventilated dogs. Tension of the tracheal smooth muscle (TSM),
      arterial blood pressure, and phrenic nerve activity (PNA) were measured during
      stimulation of the proximal end of the transected femoral nerve (FNS) with train
      pulses (duration; 0.5 ms, frequency; 40 Hz). With low intensity (e.g., 0.62 V)
      FNS, TSM exhibited relaxation, arterial pressure decreased, and neural
      respiratory output (NRO) was reduced (3 of 8 dogs) or unchanged (5 of 8 dogs).
      With increases in stimulus intensity, TSM always exhibited relaxation while
      arterial pressure and NRO exhibited excitatory responses almost at the same
      thresholds (approximately 5 V). The TSM relaxation and the excitatory NRO and
      arterial responses augmented with increases in stimulus intensity up to 16 times
      of threshold of the excitatory NRO response. TSM response was blocked by
      intravenous atropine but pressor response and phrenic response were not. The
      arterial response disappeared after administration of a ganglionic blocker. These
      findings suggest that TSM, arterial pressure, and PNA may be controlled by one
      neuronal mechanism during high intensity FNS, but that arterial pressure and PNA
      may be modified by another mechanism in an inhibitory direction when the stimulus
      intensity is low. This study suggested the existence of a neural mechanism which
      controls the airway and cardiorespiratory systems properly to execute exercise.
      Physiological significance of the responses to low intensity femoral nerve
      stimulation was uncertain.

PMID- 8988442
TI  - Similarities and differences in the time course of mechanical activity of the
      canine myocardium and isovolumic left ventricle.
AB  - BACKGROUND: The isovolumic non-ejecting left ventricle (LV) is functionally
      analogous to the isometric myocardium and the curve of the time course of left
      ventricular isovolumic pressure, P(t), resembles the curve of the time course of
      myocardial isometric force, F(t). In this study therefore, we first tested the
      hypothesis that the same general empirical model that fit F(t) and L(t), the
      isotonic shortening curve, will also fit P(t) by evaluating the model P(t) = P0 +
      C(t/A)B exp[1-(t/A)]B in 8 Suga-Sagawa isolated cross-circulated canine left
      ventricles. P0 is the end-diastolic pressure; A, B, and C are parameters. We went
      further to compare the time course of P(t) to those of F(t) and L(t) exploiting
      their common basic analytical models not only to characterize similarities but
      also to highlight differences between them. METHODS: To obtain curves of P(t), we
      inserted a latex balloon in the LV and injected water into it and recorded the
      isovolumic pressure curve, P(t), in each of 8 ventricles. Eight in situ right
      ventricular papillary muscles of the isolated canine heart were also studied with
      a servo system that clamped length or force to produce F(t) or L(t). Each curve,
      P(t), F(t), or L(t) was fit with the above model by Marquardt's algorithm and A,
      B, and C determined. RESULTS: The model fit the curves closely, the coefficient
      of determination being 0.995 +/- 0.003 for P(t); 0.994 +/- 0.003 for F(t), and
      0.990 +/- 0.004 for L(t). The common model allowed direct quantitative comparison
      of the time course of either myocardial isometric or isotonic dynamics with the
      time course of left ventricular isovolumic dynamics by comparing the ventricular
      parameters A and B, which determine details of time course, with their
      corresponding myocardial counterparts. Under basal (i.e. control) conditions, A
      and B averaged 0.194 +/- 0.015 and 2.09 +/- 0.065 respectively for P(t). Mean A
      for isotonic shortening was 0.219 +/- 0.022 (p < 0.02 compared to mean A for
      P(t)). Mean B for F(t) was 1.87 +/- 0.100 (p < 0.001 compared to mean B for
      P(t)). The values of A for P(t) and F(t) were not different and the values of B
      for P(t) and L(t) were closely similar. CONCLUSION: The same empirical model that
      fits F(t) and L(t) also fits P(t). Comparison of myocardial to ventricular curves
      showed that during contraction, P(t) corresponded closely to F(t) and L(t).
      However during relaxation, P(t) led both F(t) and L(t) both of which pursued a
      similar time course. This suggests that myocardial contraction may be isometric
      during LV isovolumic contraction and it may be valid to extrapolate information
      about myocardial isometric contraction directly to left ventricular isovolumic
      contraction and vice versa. On the other hand during left ventricular isovolumic
      relaxation, myocardial dynamics may well involve some length changes. It is
      difficult, however, to reconcile such presumed length changes to the putative
      isometricity of myocardial function during contraction.

PMID- 8988443
TI  - Two types of stretch-activated channel activities in guinea-pig gastric smooth
      muscle cells.
AB  - Using cell-attached patch-clamp techniques, stretch-activated channels were
      investigated in guinea-pig gastric smooth muscle cells. Suction applied to the
      pipette interior or cell swelling induced by hypotonic bath solution induced two
      kinds of channel openings, a short-lasting and small opening (OS) and a long
      lasting and large opening (OL) with conductances of 33 and 53 pS, respectively.
      Threshold suction for OS was lower than that for OL. In many patches examined, OS
      and OL coexisted. The distributions of open- and closed-times of OS could be
      fitted by the sum of two exponentials, the time constants of which were 1.3 and
      9.3 ms for the open-time, and 0.6 and 8.4 ms for the closed-time. Both OS and OL
      were blocked by 100 microM Gd3+ in the pipette. The reversal potentials did not
      change upon altering [Cl-]o. The results indicate that OS and OL seem to
      represent non-selective cation channel activities, which do not discriminate
      among K+, Na+, and Ca2+. These channels may play an important role in the stretch
      induced contraction in gastric muscle.

PMID- 8988444
TI  - Melatonin accelerates reentrainment of circadian locomotor activity rhythms to
      new light-dark cycles in the rat.
AB  - We examined whether continuous melatonin administration through subcutaneously
      implanted silastic tubing accelerates reentrainment of circadian rhythms of
      locomotor activity to shifted illumination cycles. We found that rats required
      less time to reentrain to an advanced or delayed phase shift of a light-dark
      cycle while carrying a silastic implant filled with melatonin than while carrying
      an empty implant. These results suggest that continuous administration of
      melatonin accelerates the reentrainment of the circadian locomotor activity
      rhythm to a new light-dark cycle.

PMID- 8988445
TI  - Interaction between the L-type Ca2+ channel and the Ca(2+)-activated K+ channel
      in the fluctuating myogenic contraction in the rabbit basilar artery.
AB  - Ring preparations of the rabbit basilar artery spontaneously developed a
      fluctuating contraction that was not inhibited by the removal of the endothelium
      or by blockade of the synthesis or action of neurotransmitters and prostanoids.
      Nifedipine greatly relaxed the spontaneously-developed contraction.
      Charybdotoxin, an antagonist of the Ca(2+)-activated K+ channel, converted the
      fluctuating contraction to a tonic contraction, whereas the ATP-sensitive K+
      channel blocker, glibenclamide, had no effect. These results indicate that the
      increased Ca2+ influx via the L-type Ca2+ channel in the rabbit basilar artery
      may induce myogenic contraction and consequently activate the Ca(2+)-activated K+
      channel, which might lead to the fluctuation of the contraction by feedback
      regulation of the Ca2+ channel.

PMID- 8988447
TI  - Bipolar II disorder: a progress report.

PMID- 8988446
TI  - Physiological requirement of aldosterone action on the Na+/K+ pump in ADH
      stimulated Na+ absorption in renal epithelium.
AB  - Short-circuit current measurement in renal epithelium (A6) indicated that the
      amount of antidiuretic hormone-stimulated Na+ entry in aldosterone-treated cells
      exceeded the ability of the Na+/K(+)-pump to extrude Na+ in aldosterone-untreated
      cells. This suggests that, if aldosterone has no stimulatory action on Na+/K(+)
      pump activity, the activity of Na+/K(+)-pump is not large enough to extrude Na(+)
      entering through antidiuretic hormone-activated Na(+)-permeant channels in the
      apical membrane. The present study concludes that the stimulatory action of
      aldosterone on the Na+/K+ pump is a physiological requirement in antidiuretic
      hormone-stimulated Na+ absorption.

PMID- 8988448
TI  - Cerebral hypoperfusion in medication resistant, depressed patients assessed by
      Tc99m HMPAO SPECT.
AB  - Functional imaging studies generally show decreased cerebral metabolism and
      perfusion in depressed patients relative to normal controls, although the
      location of the deficits varies. We used Tc99m HMPAO SPECT to compare cerebral
      blood flow in medication resistant, depressed patients and a normal control
      group. HMPAO uptake ratios (adjusted for age) were significantly lower in the
      depressed patients in the transaxial slices 4 cm and 6 cm above the orbitomeatal
      line (OML) on the left side. Examining individual regions of interest (corrected
      for age and multiple testing), we found significantly lower perfusion in the left
      superior temporal, right parietal and bilateral occipital regions in the patient
      group. These findings are in limited agreement with previous HMPAO SPECT studies.
      Methodological differences between studies, particularly variability in adjusting
      data for age, lead to a divergence in findings. Future research should seek to
      standardize protocols and data analysis in order to generate comparable results.

PMID- 8988449
TI  - Effects of childbearing on the natural history of panic disorder with comorbid
      mood disorder.
AB  - This historical prospective study included 22 women with panic disorder. They
      experienced 45 pregnancies associated with or after their first lifetime episode
      of panic disorder. Mood disorder predated or was associated with 32 of these
      pregnancies. The most common effect of pregnancy was No Change in symptoms from
      baseline during pregnancy and continued No Change postnatally for both panic
      attacks (n = 22; 49%) and depression (n = 19; 59%). The pattern of panic attack
      across gestations was consistent for only 5 of 14 multiparae. An interesting
      observation was that first lifetime onset of panic disorder was common postpartum
      (n = 4) or post-miscarriage (n = 2). First-onset depression was also common
      postpartum (n = 4).

PMID- 8988451
TI  - The Seasonal Pattern Assessment Questionnaire for identifying seasonal affective
      disorders.
AB  - The SPAQ is a widely used tool for identifying possible cases of recurrent major
      depressive disorders with a seasonal pattern. However, its test-retest
      reliability, sensitivity, specificity, positive predictive value, negative
      predictive value, efficiency and predictive validity have not previously been
      formally assessed. Forty-seven subjects who fulfilled the DSMIIIR criteria for a
      major depressive disorder with a seasonal pattern were traced and re-interviewed
      after five to eight years. The SPAQ was found to have a positive predictive value
      of 48% and an efficiency of 57% in identifying cases of SAD confirmed by follow
      up. The test-retest reliability was low. There was a mean difference in
      seasonality score between the first and second test of 3.17 +/- 4.7 (mean +/- 1
      S.D.). Although the SPAQ is a rapid method of collecting information about recent
      seasonal variation, it has low test-retest reliability and on its own is unable
      to predict the seasonality of the future course of illness.

PMID- 8988450
TI  - Clinical presentations of major depression by African Americans and whites in
      primary medical care practice.
AB  - This study compared the psychiatric history and presenting clinical
      characteristics of 119 African American and 153 white patients assessed for and
      participating in a randomized control trial of treatments for major depression in
      primary care practice. African Americans and whites participated equally in the
      assessment process, and both groups presented with similar psychiatric treatment
      histories, severity of depression, level of psychosocial functioning, and
      severity of medical illness. However, racial differences were evident in the
      comorbidity of psychiatric disorders, severity of somatic symptoms, self-reported
      physical functioning, life stress, and health beliefs. Implications for the
      recognition of depression in African American primary care patients are
      discussed.

PMID- 8988452
TI  - Efficacy of treatment with trazodone in combination with pindolol or fluoxetine
      in major depression.
AB  - Fluoxetine, a selective serotonin (5-HT) reuptake inhibitor (SSRI), and
      trazodone, a heterocyclic antidepressant, are effective in the treatment of major
      depression and treatment resistant depression (TRD). Chronic treatment with both
      drugs causes increases in extracellular 5-HT through 5-HT reuptake inhibition and
      desensitization of inhibitory 5-HT1A autoreceptors. It has been shown that
      pindolol, a serotonin (5-HT)1A-receptor antagonist, may shorten the latency of
      onset of SSRIs in depression. The aim of the present study was to examine whether
      pindolol may increase the efficacy of a subtherapeutical dosage of trazodone in
      the treatment of major depression and TRD, defined according to the Thase and
      Rush criteria (1995). Thirty-three major depressed inpatients of whom 26 with TRD
      participated in this study. Ten days after hospitalization, treatment with
      trazodone 100 mg/day was started. After 1 week trazodone treatment, patients were
      randomized-using a double blind placebo controlled design-to receive trazodone
      100 mg/day+placebo; trazodone 100 mg/day+pindolol 7.5 mg/day: or trazodone 100
      mg/day+fluoxetine 20 mg/day and treated during 4 weeks. The 17-item Hamilton
      Depression Rating Scale (HDRS) was used as outcome measure. It was found that
      trazodone+pindolol was as effective as trazodone+fluoxetine in the treatment of
      major depression and TRD and significantly more effective than trazodone+placebo.
      Using an outcome measure of 50% reduction in the HDRS, we found that 72.5% of the
      depressed patients treated with trazodone+pindolol and 75% of depressed patients
      treated with trazodone+fluoxetine showed a clinically significant response
      compared with 20.0% of trazodone+placebo-treated patients.

PMID- 8988453
TI  - "Normal' P300 amplitude predicts rapid response to ECT in melancholia.
AB  - Consenting melancholic depressives (n = 17) were treated with bilateral ECT under
      anaesthesia. All patients except two were antidepressant-naive. The auditory P300
      event-related potential (ERP) was recorded before and after the ECT course. The
      latency of P300 in depressives before treatment did not differ from controls, but
      the amplitude was smaller than in matched controls (n = 15). The P300 amplitude
      was larger in depressives who had rapid response than in the rest. Rapid
      responders did not differ from controls on P300 amplitude before treatment. Hence
      it is suggested that "Normal' P300 predicts rapid therapeutic response to ECT in
      melancholia.

PMID- 8988454
TI  - Linkage studies in bipolar affective disorder with markers on chromosome 21.
AB  - Straub et al. (1994: Nature Genet. 8. 291-296) have suggested that a
      susceptibility gene for bipolar affective disorder is located at chromosome
      21q22.3, on the basis of linkage analysis in one large family. This result has
      been supported by Gurling et al. (1995: Nature Genet. 10, 8-9) who also found
      some evidence for linkage to this region under locus heterogeneity. In order to
      investigate the validity of these results and to estimate how broadly applicable
      they are, we performed a linkage study between bipolar affective disorder and two
      DNA markers (D21S171 and PFKL) from 21q22.3 using 60 bipolar pedigrees from three
      European centres and Brazil. The most positive result obtained was a maximised
      admixture lod score of 1.2 for the marker PFKI, under the assumption of locus
      heterogeneity, dominant transmission and a diagnostic classification which
      included recurrent unipolar depression. However, since lod scores obtained for
      both markers were substantially negative overall, we conclude that there is no
      common major gene for bipolar affective disorder at 21q22.3. It remains possible
      that a gene of major effect in this region operates in a minority of families.

PMID- 8988455
TI  - Recognition and management of major depression in psychiatric outpatient care: a
      questionnaire survey.
AB  - We studied the ability of psychiatric practitioners to recognize and treat major
      depression in standard clinical practice in Finland. A questionnaire with 18
      items (including, e.g. physicians characteristics, two case reports and
      diagnostic and treatment proposals for both of them) was sent to 255 physicians
      in communal psychiatric outpatient care, 216 physicians responded (85%). Results
      suggest that diagnostic accuracy was good. Treatment proposals showed high
      sensitivity and lower specificity when the use of antidepressive medication was
      examined. This may reflect increased education concerning the illness and the
      effect of the new antidepressants, which are probably considered easier to
      initiate, or may be partly due to systematic error. Physicians characteristics
      determined neither diagnostic nor treatment decisions.

PMID- 8988456
TI  - Personality: a moderator of the relation between cognitive functioning and
      depression in adults aged 55-85?
AB  - Previous studies found modest associations between cognitive functioning and
      depressive symptoms in community samples of older adults. Low levels of cognitive
      functioning are associated with depressive symptoms. The present study
      investigates whether personality (locus of control and neuroticism) moderates
      this relation, and whether gender-differences in moderating effects can be
      established. The study is based on data of the baseline sample of 3107
      participants of the Longitudinal Aging Study Amsterdam (LASA), which was age (55
      85 years) and sex-stratified. Multiple regression analyses are used to detect
      moderating effects. The findings show modest effects, indicating that personality
      is a moderator of the relation between cognitive functioning and depressive
      symptoms, particularly in women. In women, a relatively strong internal locus of
      control is protective of becoming depressed when experiencing impairment in
      general cognitive functioning (MMSE), and impairment in fluid intelligence and
      information processing speed. In men, a low level of neuroticism is protective of
      becoming depressed when experiencing memory impairment. If these findings are
      replicated and extended in future studies, pertinent interventions such as
      cognitive therapy or memory training may be designed to alleviate depressive
      symptoms.

PMID- 8988457
TI  - New aspects of pathology in Parkinson's disease with concomitant incipient
      Alzheimer's disease.
AB  - Alzheimer's disease and Parkinson's disease are the most common age-related
      degenerative disorders of the human brain. Both diseases involve multiple
      neuronal systems and are the consequences of cytoskeletal abnormalities which
      gradually develop in only a small number of neuronal types. In Alzheimer's
      disease, susceptible neurons produce neurofibrillary tangles and neuropil
      threads, while in Parkinson's disease, they develop Lewy bodies and Lewy
      neurites. The specific lesional pattern of both illnesses accrues slowly over
      time. Presently available data support the view that fully developed Parkinson's
      disease with concurring incipient Alzheimer's disease is likely to cause impaired
      cognition.

PMID- 8988458
TI  - New horizons in molecular mechanisms underlying Parkinson's disease and in our
      understanding of the neuroprotective effects of selegiline.
AB  - There have been many claims that the selective monoamine oxidase type B (MAO-B)
      inhibitor selegiline may have distinct properties in slowing the progression of
      Parkinson's disease (PD). Degeneration of nigro-striatal dopaminergic neurons is
      the primary histopathological feature of PD. Although many different hypotheses
      have been advanced, the cause of chronic nigral cell death and the underlying
      mechanisms remain elusive as yet. Therefore, there is no clear knowledge
      regarding an understanding of the reported effects of selegiline on the
      progression of PD. However, there is a considerable body of indirect evidence
      that oxidative stress may play a role in the pathogenesis of this illness.
      Oxidative stress refers to cytotoxic consequences of hydrogen peroxide and oxygen
      derived free radicals such as the hydroxyl radical (.OH), the superoxide anion
      (.O2), and nitric oxide (NO), which are generated as byproducts of normal and
      aberrant metabolic processes that utilize molecular oxygen. On the other hand, an
      increasing body of experimental data has implicated excitotoxicity as a mechanism
      of cell death in both acute and chronic neurological disease. One of the receptor
      which is particularly involved in the toxic effects of excitatory amino acids is
      the NMDA (N-methyl-D-aspartate) receptor. Excessive stimulation of this type of
      receptor by glutamic acid or NMDA agonists leads to a massive influx of calcium
      ions into the neuron followed by activation of a variety of calcium-dependent
      enzymes, impaired mitochondrial function, and the generation of free radicals.
      This article will consider the concept that excitotoxicity is linked with the
      generation of free radicals. In view of this idea it will be further discussed
      how selegiline might exert its neuroprotective effects via indirect actions on
      the polyamine binding site of the NMDA receptor. Under treatment with the MAO-B
      inhibitor selegiline, the degradation of putrescine via MAO, a key factor in
      regulating the polyamine metabolism, might be diminished in the Parkinsonian
      brain, which in turn would suppress the polyamine synthesis. Hence, the reported
      neuroprotective effect of selegiline might also receive a contribution from the
      diminished potentiation of the NMDA receptor by the polyamine binding site. On
      the other hand, since N1-acetylated spermine and spermidine are also good
      substrates of MAO-B, it is likely that these compounds will be present in the
      brain in increased concentrations. It therefore seems possible that they will
      exert a neuroprotective effect via an antagonistic modulation of the polyamine
      binding site of the NMDA receptor.

PMID- 8988459
TI  - Early diagnosis in Parkinson's disease--limitation of biochemical markers and
      instrumental methods.
AB  - For most cases of Parkinson's disease (PD) we can estimate the time lag from the
      first onset of unspecific complaints until diagnosis by case history to be about
      2 years. Until now the exact course of neurodegeneration in PD is still unknown.
      On base of recent knowledge we can discuss different models for the development
      of PD. There are substantially different possible approaches to recognise PD as
      soon as possible. The time interval for an earlier diagnosis is different for
      these methods and depends on the real course of neurodegerdation.

PMID- 8988460
TI  - The pharmacology of B-type selective monoamine oxidase inhibitors; milestones in
      (-)-deprenyl research.
AB  - (-)-deprenyl cannot be considered as a simple, selective inhibitor of MAO-B. It
      increases the dopaminergic tone in the central nervous system by a complex
      mechanism. The MAO-B inhibition could result in a potentiation of the effect and
      the reduction of the dose of L-dopa, including the restoration of the sensitivity
      to L-dopa treatment, when the response to the drug has already been diminished or
      lost. Pre-treatment with (-)-deprenyl prevent the effect of neurotoxins like
      MPTP, 6-hydroxydopamine, DSP-4, AF64A by inhibiting the conversion of the
      pretoxin to toxin, or by inhibiting the neuronal reuptake mechanisms, or the
      combination of the two processes. However, other effects of the inhibitor cannot
      be ruled out. (-)-deprenyl, but not its (+)-enantiomer, proved to be a potent
      inhibitor of programmed cell death (apoptosis) of PC12 cells and that of human
      melanoma cells, in a concentration which does not induce MAO-B inhibition. The
      activity of MAO-B increases with age and the age related changes led to an
      overproduction of neurotoxic agents. The inhibition of the enzyme activity can
      play a preventive role against neurodegenerative brain disorders. The most widely
      used MAO-B inhibitor in the therapy is (-)-deprenyl and it lacks the "cheese
      reaction". The complex mechanism for the lack of the former effect is not fully
      known.

PMID- 8988461
TI  - (-)-Deprenyl reduces neuronal apoptosis and facilitates neuronal outgrowth by
      altering protein synthesis without inhibiting monoamine oxidase.
AB  - (-)-Deprenyl stereospecifically reduces neuronal death even after neurons have
      sustained seemingly lethal damage at concentrations too small to cause monoamine
      oxidase-B (MAO-B) inhibition. (-)-Deprenyl can also influence the process growth
      of some glial and neuronal populations and can reduce the concentrations of
      oxidative radicals in damaged cells at concentrations too small to inhibit MAO.
      In accord with the earlier work of others, we showed that (-)-deprenyl alters the
      expression of a number mRNAs or proteins in nerve and glial cells and that the
      alterations in gene expression/protein synthesis are the result of a selective
      action on transcription. The alterations in gene expression/protein synthesis are
      accompanied by a decrease in DNA fragmentation characteristic of apoptosis and
      the death of responsive cells. The onco-proteins Bcl-2 and Bax and the scavenger
      proteins Cu/Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD2) are
      among the 40-50 proteins whose synthesis is altered by (-)-deprenyl. Since
      mitochondrial ATP production depends on mitochondrial membrane potential (MMP)
      and mitochondrial failure has been shown to be one of the earliest events in
      apoptosis, we used confocal laser imaging techniques in living cells to show that
      the transcriptional changes induced by (-)-deprenyl are accompanied by a
      maintenance of mitochondrial membrane potential, a decrease in intramitochondrial
      calcium and a decrease in cytoplasmic oxidative radical levels. We therefore
      propose that (-)-deprenyl acts on gene expression to maintain mitochondrial
      function and to decrease cytoplasmic oxidative radical levels and thereby to
      reduce apoptosis. An understanding of the molecular steps by which (-)-deprenyl
      selectively alters transcription may contribute to the development of new
      therapies for neurodegenerative diseases.

PMID- 8988462
TI  - Are metabolites of l-deprenyl (selegiline) useful or harmful? Indications from
      preclinical research.
AB  - A frequent topic of controversy has been whether metabolism of l-deprenyl
      (selegiline) to active metabolites is a detriment to clinical use. This paper
      reviews possible roles of the metabolites of l-deprenyl in producing unwanted
      adverse side effects or in augmenting or mediating its clinically useful actions.
      Levels of l-amphetamine and l-methamphetamine likely to be reached, even with
      excessive intake of l-deprenyl, would be unlikely to produce neurotoxicity and
      there is no preclinical or clinical evidence of abuse liability of l-deprenyl. In
      contrast, there is evidence that l-amphetamine and l-methamphetamine have some
      qualitatively different actions than their d-isomer counterparts on EEG and
      cognitive functioning which might result in beneficial clinical effects and
      complement beneficial clinical actions of l-deprenyl itself.

PMID- 8988463
TI  - Deprenyl in the treatment of Parkinson's disease: clinical effects and
      speculations on mechanism of action.
AB  - Selegiline is a relatively selective inhibitor of monoamine oxidase type B that
      has been used in Parkinson's disease as an adjunct to levodopa and as putative
      neuroprotective therapy. Clinical trials demonstrate that selegiline slows the
      rate of disease progression and delays the appearance of disability necessitating
      levodopa. However, confounding symptomatic effects have made it difficult to
      ascertain the presence of any direct neuroprotective effect. Laboratory studies
      demonstrate that selegiline protects dopaminergic neurons through a mechanism
      that does not involve MAO-B inhibition. Recent studies suggest that
      neuroprotection in laboratory models may be related to the capacity of selegiline
      to up-regulate a series of anti-oxidant and anti-apoptotic molecules which
      promote cell survival. Further delineation of the precise mechanism whereby
      selegiline induces this effect may permit for the development of enhanced
      neuroprotective benefits in PD patients.

PMID- 8988464
TI  - The clinical potential of Deprenyl in neurologic and psychiatric disorders.
AB  - This article reviews the results of clinical studies with Deprenyl in various
      neurologic and psychiatric disorders except Parkinson's disease. Promising
      results could be observed both in narcolepsy in a dose of at least 20 mg/day in
      three different trials and in one study of Tourette's syndrome including
      attention hyperactivity disorders using an average dosis of 8.1 mg/ day.
      Controversial results were reported for Alzheimer's disease. On the one hand
      significant improvement of cognitive functions was found by various authors. On
      the other hand in a more recent study no effect on the progression of the disease
      could be observed. For depression a higher dosage of deprenyl between 30 to 60
      mg/day appears to be necessary for effective treatment. No positive results were
      found in amyotrophic lateral sclerosis and in tardive dyskinesias.

PMID- 8988465
TI  - Pharmacology and neuroprotective properties of rasagiline.
AB  - Rasagiline [R(+)-N-propargyl-1-aminoindane] is a selective irreversible inhibitor
      of MAO-B which is not metabolised to amphetamine-like derivatives. Like deprenyl,
      when given to rats in a dose selective for inhibition of MAO-B, it does not
      affect striatal extracellular fluid dopamine levels, but when administered
      chronically (21 days) it increased striatal microdialysate dopamine without
      reduction in deaminated metabolites. Similarly to deprenyl, rasagiline (10(-6)M)
      increased the percentage of tyrosine hydroxylase positive cells in a primary
      culture of rat fetal mesencephalic cells (6 days in culture). Rasagiline, but not
      deprenyl, also increased the number of neurons per field in this organotypic
      culture.

PMID- 8988466
TI  - Potential of neurotrophic factors in therapy of Parkinson's disease.
AB  - Neurotrophic factors of dopaminergic neurons may represent a potential
      neuroprotective therapy for PD. This article reviews published experiments that
      demonstrate the effects of neurotrophic factors on dopaminergic neurons in vitro
      and in vivo. At present this issue is predominantly investigated in basic
      neuroscientific research. Its possible future clinical relevance is discussed.

PMID- 8988467
TI  - Telemedicine expanding the scope of health care information.
AB  - The definition of health information is growing to include multimedia audio,
      video, and high-resolution still images. This article describes the telemedicine
      program at East Carolina University School of Medicine, including the
      telemedicine applications presently in use and the virtual reality applications
      currently under development' Included are the major design criteria that shape
      the telemedicine network some of the lessons learned in developing the network,
      and a discussion of the future of telemedicine, including efforts to incorporate
      telemedicine within a fully integrated health information system.

PMID- 8988468
TI  - Approaching equity in consumer health information delivery: NetWellness.
AB  - The growing public interest in health and wellness information stems from many
      sources, including social changes related to consumers' rights and women's health
      movements, and economic changes brought about by the managed health care
      revolution. Public, hospital, and medical center libraries have been ill-equipped
      to meet the increasing need for consumer-oriented materials, even though a few
      notable programs have been established. The "Information Superhighway" could be
      an effective tool for sharing health information if access to telecomputing
      equipment and training were available to those with an information need. The
      University of Cincinnati Medical Center, with its libraries in the leading role,
      is delivering NetWellness, an electronic consumer health library service, to
      residents of 29 counties in three midwestern states. Users connect directly
      through the Internet, through regional Free-Nets, and by visiting one of 43
      public access sites where networked workstations have been installed. The
      continued success of the project depends on developing partnerships, providing
      quality content and maintaining fair access.

PMID- 8988469
TI  - Implementation of in-home telemedicine in rural kansas: answering an elderly
      patient's needs.
AB  - The Interactive Home Health Care Program is a demonstration project evaluating
      the use of in-home telemedicine to provide health care for elderly and disabled
      people. Local cable systems interconnect a base station staffed by a telemedicine
      nurse with a modified television in the home. Six months into the project, 38
      patients are being cared for at three sites in rural Kansas. Individual patient
      profiles show improvement. Technical and social challenges appear solvable. An
      evaluation is in progress.

PMID- 8988470
TI  - The implementation of telemedicine within a community cancer network.
AB  - Telemedicine is being used by physicians at the member hospitals of the Jefferson
      Cancer Network (JCN) for consultations regarding the diagnosis and management of
      cancer patients. The technology employed for this telemedicine system was chosen
      to meet three related specifications: low capital and operating cost, internal
      maintainability by community hospital data processing staffs, and compatibility
      with the existing technologic infrastructure. The solution selected is the
      ubiquitous desktop personal computer and associated software, and Integrated
      Services Digital Network (ISDN) communications links. The overall performance of
      this technology has been very satisfactory; ISDN communications has sufficient
      bandwidth for the transfer of patient data, including text reports, radiographs,
      and pathology slide images. The presence of the radiologist's interpretation
      along with the radiographic images allows the presentation of the images on these
      systems to be acceptable for review purposes. The video frame rates of these
      systems (12 to 15 frames per second) is adequate, particularly given the "talking
      heads" nature of the video presentations. Furthermore, the quality of the video
      image (resolution, size, frame rate) is secondary to the quality of the
      presentation of the medical information displayed and the capability for mutual
      annotation of the patient data during the consultation.

PMID- 8988471
TI  - Electronic clinical trial protocol distribution via the World-Wide Web: a
      prototype for reducing costs and errors, improving accrual, and saving trees.
AB  - Clinical trials today typically are inefficient, paper-based operations. Poor
      community physician awareness of available trials and difficult referral
      mechanisms also contribute to poor accrual. The Physicians Research Network (PRN)
      web was developed for more efficient trial protocol distribution and eligibility
      inquiries. The Medical University of South Carolina's Hollings Cancer Center
      trials program and two community oncology practices served as a testbed. In 581
      man-hours over 18 months, 147 protocols were loaded into PRN. The trials program
      eliminated all protocol hardcopies except the masters, reduced photocopier use
      59%, and saved 1.0 full-time equivalents (FTE), but 1.0 FTE was needed to manage
      PRN. There were no known security breaches, downtime, or content-related
      problems. Therefore, PRN is a paperless, user-preferred, reliable, secure method
      for distributing protocols and reducing distribution errors and delays because
      only a single copy of each protocol is maintained. Furthermore, PRN is being
      extended to serve other aspects of trial operations.

PMID- 8988472
TI  - Rural telemedicine data/image transfer methods and purposes of interactive video
      sessions.
AB  - A national survey conducted for the Office of Rural Health Policy in 1995
      identified 558 participants in rural telemedicine; 499 (89%) responded to a
      detailed follow-up survey to describe type of use. While 84% of respondents
      reported using interactive video, only 25% reported access to e-mail for exchange
      of data. The challenge to medical informatics is to connect dispersed providers,
      not just with videoconferencing, but also with other information-sharing methods.

PMID- 8988473
TI  - Symbolic anatomic knowledge representation in the Read Codes version 3: structure
      and application.
AB  - The Read Thesaurus (Version 3 of the Read Codes) is a controlled medical
      vocabulary produced during the Clinical Terms Projects with the involvement of
      over 2,000 health care professionals from all United Kingdom specialties. In
      addition to allowing the transfer of clinical information in a meaningful way, it
      supports analysis of this information and provides a basis for the development of
      shareable medical knowledge bases. The thesaurus includes a comprehensive,
      dynamic set of over 7,000 gross anatomic concepts richly linked in a network with
      over 16,000 operative procedures and 40,000 disorders. The representation of
      anatomic concepts aims to balance the requirements for expressivity, clearness,
      and simplicity. The underlying directed acyclic graph hierarchy is independent of
      the alphanumeric code and enables continued refinement and expansion. A template
      table allows semantic definition, qualification, and linkage of concepts.

PMID- 8988474
TI  - Automated computer interviews to elicit utilities: potential applications in the
      treatment of deep venous thrombosis.
AB  - OBJECTIVE: To assess the practicality of an automated computer interview as a
      method to assess preferences for use in decision making. To assess preferences
      for outcomes of deep vein thrombosis (DVT) and its treatment. STUDY DESIGN: A
      multimedia program was developed to train subjects in the use of different
      preference assessment methods, presented descriptions of mild post-thrombotic
      syndrome (PTS), severe PTS and stroke and elicited subject preferences for these
      health states. This instrument was used to measure preferences in 30 community
      volunteers and 30 internal medicine physicians. We then assessed the validity of
      subject responses and calculated the number of quality-adjusted life years
      (QALYs) for each individual for each alternative. RESULTS: All subjects completed
      the computerized survey instrument without assistance. Subjects generally
      responded positively to the program, with volunteers and physicians reporting
      similar preferences. Approximately 26.5% of volunteers and physicians had
      preferences that would be consistent with the use of thrombolysis.
      Individualization of therapy would lead to the most QALYs. CONCLUSIONS:
      Utilization of computerized survey instruments to elicit patient preferences
      appears to be a practical and valid approach to individualize therapy.
      Application of this method suggests that there may be many patients with DVT for
      whom treatment with a thrombolytic drug would be optimal.

PMID- 8988475
TI  - Preparing librarians to meet the challenges of today's health care environment.
AB  - OBJECTIVE: Refine the understanding of the desirable skills for health sciences
      librarians as a basis for developing a training program model that reflects the
      fundamental changes in health care delivery and information technology. DESIGN: A
      four-step needs assessment process: focus groups developed lists of desirable
      skills; the research team organized candidate skills into a taxonomy; a survey of
      a random sample of librarians and library users assessed perception of importance
      of individual skills; and the research team framed, as a unifying hypothesis, a
      training model. SURVEY METHODS: The survey was distributed to random samples of
      150 librarians, stratified by type of library, and 150 library users, stratified
      by type of use. A non-randomized sample was obtained by mounting the survey on a
      World Wide Web server. The survey instrument included 96 distinct skills
      organized into 13 categories. Respondents rated the importance of each skill on a
      Likert scale and provided a separate ranking by identifying the ten most
      important skills for the profession. RESULTS: Among the participants, 51% of
      librarians and 36% of library users responded to the survey. All categories of
      skills were rated above the midpoint of priority on the Likert scale. All groups
      rated personality characteristics and skills as most important, with an
      understanding of the health sciences, education, and research being rated
      comparably to technical skills. CONCLUSIONS: Health sciences librarians need a
      new educational model that provides them with broad-based tools to discover new
      roles and new resources for acquiring individual skills as the need arises. A
      unifying training model would involve trainees in developing their learning plan
      in a way that promotes proactive inquiry and self-directed learning, and it would
      rotate the trainees through projects to provide skills and an understanding of
      end-user work processes.

PMID- 8988476
TI  - Telehealth: the need for evaluation.

PMID- 8988477
TI  - Renal nerve responses to somatic nerve activation in stroke-prone spontaneously
      hypertensive rats.
AB  - In chloralose/urethane anaesthetised stroke-prone spontaneously hypertensive
      rats, blood pressure and integrated renal nerve activity were higher whereas
      heart rate was lower than in Wistar rats by 37, 146 and 11%, respectively (all P
      < 0.001). The renal nerve signal was subjected to fast Fourier transformation to
      generate power spectra. In the hypertensive rats, total spectral power was 400%
      (P < 0.01) and power at the heart rate frequency was 50% (P < 0.01) greater while
      phase and time differences were shorter (both P < 0.001) than in Wistar rats.
      Brachial nerve stimulation increased total power in Wistar and hypertensive rats
      (P < 0.05), but importantly, power at the heart rate frequency was decreased by
      80% in Wistar whereas there was a 20% (P < 0.05) increase in hypertensive rats,
      while phase and time differences were raised only in hypertensive rats (P <
      0.05). Bilateral cervical vagotomy of the hypertensive rats had minimal actions
      on most variables but phase and time differences were doubled compared to intact
      hypertensive animals, but brachial nerve stimulation decreased power at the heart
      rate frequency (P < 0.05) which was a very different response from intact rats.
      Resting blood pressure, heart rate, total power and power at the heart rate
      frequency in the carotid sinus denervated animals were lower than in intact
      hypertensive rats, between 17 and 71%, respectively, but increased during
      brachial nerve stimulation. These experiments demonstrated that whereas somatic
      sensory input can modulate the pattern of sympathetic nerve activity to the
      kidney under normal conditions, this does not occur in the hypertensive rat. This
      appears to be related to afferent information carried by the vagus which
      suppresses the normal response; the carotid sinus baroreceptors are devoted to
      organising the nerve activity in relation to the blood pressure pulse wave.

PMID- 8988478
TI  - Corticotropin releasing factor-like immunoreactivity in afferent projections to
      the sacral spinal cord of the cat.
AB  - Distribution and origin of corticotropin releasing factor (CRF) in the thoraco
      lumbar and sacral spinal cord of the cat has been studied using
      immunohistochemical method. CRF immunoreactive (CRF-IR) nerve fibers and
      terminals were most prominent in dorsal part of sacral spinal cord. In the sacral
      segments of the spinal cord, immunoreactivity for CRF was detected in a prominent
      bundle of axons and varicosities extending from Lissauer's tract (LT) along the
      lateral edge of the superficial dorsal horn (laminae I and II) to laminae V at
      the base of the dorsal horn. Individual CRF-IR fibers passed from the bundle in
      ventral medial and ventrolateral directions to the dorsal commissure and the
      sacral preganglionic nucleus (SPN), respectively. The bundle of CRF-IR axons
      closely resembled vasoactive intestinal polypeptide (VIP) containing fibers in LT
      and on the lateral edge of the dorsal horn. Sacral dorsal root transection
      eliminated both the CRF and VIP fiber staining in the dorsal horn. Spinal
      transection at the T12-T13 segmental level did not influence the CRF- or VIP-IR.
      Less intense CRF-IR was also present in fibers in: (1) the dorsal lateral
      funiculus adjacent to LT, (2) the superficial layers of the dorsal horn and
      intermediolateral nucleus at thoracolumbar spinal levels, (3) the ventral horn,
      including Onuf's nucleus, (4) the intermediate gray matter including the dorsal
      gray commissure, and (5) the SPN. The similarity in the distribution of CRF-IR
      and pelvic nerve afferent projections in the sacral spinal cord raises the
      possibility that CRF may be a transmitter in afferent neurons innervating the
      pelvic viscera.

PMID- 8988479
TI  - Autonomic and sensory innervation of cat molar gland and blood vessels in the
      lower lip, gingiva and cheek.
AB  - Innervation of the molar gland and blood vessels in the lower lip, gingiva and
      cheek mucous membrane was investigated in the cat with the aid of whole mount
      acetylthiocholinesterase (WATChE) histochemistry and retrograde neuronal tracing
      methods with horseradish peroxidase (HRP) and HRP-conjugated wheat germ
      agglutinin (WGA-HRP). The molar gland was found to be supplied from the buccal
      nerve and branches of the mylohyoid nerve on the basis of microdissection of
      WATChE-stained mandibular preparations under a dissecting microscope. The rostral
      half of the lower lip-gingiva was innervated by mental branches from the inferior
      alveolar nerve. The caudal half of the lower lip-gingiva and cheek mucous
      membrane were observed to be supplied from the buccal nerve. Following injections
      of HRP/WGA-HRP into the molar gland, lower lip-gingiva and cheek, many
      retrogradely labeled ganglion neurons were observed in the ipsilateral main and
      accessory otic ganglia, superior cervical ganglion and mandibular division of the
      trigeminal ganglion. In the pterygopalatine ganglion, a small number of positive
      neurons were found, but in a few cases in which the injected tracer was
      restricted to the lower lip-gingiva and anterior half of the molar gland, labeled
      neurons were not detected in the main ganglion nor in its accessory microganglia.
      These findings indicate that the cat molar gland receives a postganglionic
      parasympathetic supply from the otic ganglia, postganglionic sympathetic input
      from the superior cervical ganglion and sensory innervation from the trigeminal
      ganglion by way of the buccal nerve and mylohyoid nerve. Vessels in the rostral
      half of the lower lip-gingiva receive the same inputs from the inferior alveolar
      nerve, and vessels in the caudal half receive inputs from the buccal nerve. The
      vessels in the cheek mucous membrane receive dual parasympathetic supplies from
      the otic ganglia and the pterygopalatine ganglion by way of the buccal nerve.

PMID- 8988480
TI  - Nitric oxide reduces basal efflux of catecholamines from perfused dog adrenal
      glands.
AB  - Norepinephrine, epinephrine, dopamine, and both the free and extended forms of
      [met]enkephalin spontaneously efflux from adrenal glands under basal conditions.
      The present study was done to determine whether nitric oxide has a regulatory
      role in these effluxes. Isolated adrenal glands (n = 63) from mongrel dogs were
      perfused retrogradely with Krebs-Ringer solution. In some experiments NG
      monomethyl-L-arginine (3 x 10(-4) M), an inhibitor of nitric oxide synthesis, was
      added to the perfusate. In other experiments one of the nitric oxide donors, 3
      morpholinosydnonimine (10(-7) M or 10(-5) M) or sodium nitroprusside (10(-6) M or
      10(-4) M) was added. Norepinephrine, epinephrine, dopamine and their metabolites
      3,4-dihydroxyphenylglycol and 3,4-dihydroxyphenylacetic acid in perfusates were
      quantitated by high performance liquid chromatography with electrochemical
      detection and in some experiments the [met]enkephalins were determined by
      radioimmunoassay. In the presence of NG-monomethyl-L-arginine, the basal effluxes
      of norepinephrine, epinephrine, and dopamine were significantly increased from
      control, but the effluxes of the free and extended forms of the [met]enkephalins
      were not changed. The effects of NG-monomethyl-L-arginine on catecholamine efflux
      were reversed in the presence of L-arginine (10(-3) M). Sodium nitroprusside (10(
      6) M) inhibited effluxes of norepinephrine and epinephrine and 3
      morpholinosydnonimine had no effect on these effluxes. Dopamine efflux appeared
      to be under different controls from those of norepinephrine and epinephrine since
      dopamine efflux was unaffected by sodium nitroprusside and was decreased over
      time by 3-morpholinosydnonimine (10(-7) M). It is concluded that endogenously
      produced nitric oxide inhibits the basal efflux of norepinephrine, epinephrine,
      and dopamine from isolated dog adrenal glands; this inhibition appears to be near
      maximal for norepinephrine and epinephrine but not for dopamine.

PMID- 8988481
TI  - The effect of pelvic nerve stimulation on recto-anal motility in the cat.
AB  - Rectal and anal motility responses to pharmacological manipulation of neuro
      transmission and graded efferent electrical pelvic nerve stimulation were
      investigated in alpha-1-chloralose anaesthetized cats. N omega-nitro-L-arginine
      (L-NNA), a competitive inhibitor of nitric oxide synthase, did not influence
      spontaneous rectal and anal motility. No significant change in anal pressure or
      rectal tone was observed after sectioning the pelvic nerves in animals pretreated
      with L-NNA. The effect of pelvic nerve stimulation on anal tone was varying and
      depended upon the intensity of stimulation and the prevailing anal tone. A
      reduction of anal tone on pelvic nerve stimulation was consistently converted to
      an increase of anal tone after pretreatment with L-NNA. The rectal response to
      pelvic nerve stimulation was unchanged by L-NNA. Residual increase of anal tone
      observed on pelvic nerve stimulation after L-NNA and noradrenergic blockade was
      partly sensitive to hexamethonium and abolished by atropine. The results suggest
      that there is no tonic influence on rectal and anal motility via nitric oxide
      mechanisms. On the other hand, the reduction of anal tone on high intensity
      pelvic nerve stimulation seemed to be dependent on the release of nitric oxide.
      An excitatory cholinergic component of the smooth muscle contractility of the
      feline anal canal, partly sensitive to hexamethonium, was demonstrated to be
      conveyed in the pelvic nerves.

PMID- 8988482
TI  - Nitrergic neurons in the pancreas of newborn guinea pig: their distribution and
      colocalization with various neuropeptides and dopamine-beta-hydroxylase.
AB  - The distribution of nitrergic neurons in the pancreas of the newborn guinea pig
      was first investigated, using nitric oxide synthase (NOS) immunofluorescence and
      nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d)
      histochemistry. There was total colocalization of NOS and NADPH-d in the
      pancreatic ganglion cells. NADPH-d was then used as a marker for NOS. In the
      whole mount preparation of the pancreas, most of the nitrergic neurons were
      located in the head and the body region, along the branches of pancreatic blood
      vessels. Some were also associated with the main pancreatic duct, islets of
      Langerhans and pancreatic acini. To investigate whether NADPH-d stained cells
      were neurons and whether NADPH-d was colocalized with various neuropeptides and
      dopamine-beta-hydroxylase (D beta H), an enzyme involved in the synthesis of
      noradrenaline, antibodies against neuron specific enolase (NSE), vasoactive
      intestinal peptide (VIP), neuropeptide Y (NPY). D beta H, substance P (SP),
      calcitonin gene-related peptide (CGRP) and bombesin (BOM) were used. Of all NSE
      positive ganglion cells, 76.8% were NADPH-d positive. NOS, VIP, NPY and D beta H
      immunoreactivities were found in both the neuronal cell bodies and nerve fibres
      in the pancreas while SP, CGRP and BOM immunoreactivities were detected only in
      the nerve fibres. SP-, CGRP- and BOM-containing nerves were in close contact with
      both NADPH-d positive as well as NADPH-d negative neurons. The percentages of
      NADPH-d/VIP, NADPH-d/NPY, NADPH-d/D beta H neurons in the total number of
      pancreatic neurons were 67.4%, 53.5%, 21.5% respectively. With double labelling
      in adjacent sections three subpopulations of pancreatic ganglion cells were
      demonstrated: NADPH-d/VIP/NPY, NADPH-d/VIP/D beta H and NADPH-d/NPY/D beta H.

PMID- 8988483
TI  - Comparison of inotropic and chronotropic effects of vasoactive intestinal peptide
      in isolated dog atria.
AB  - The positive chronotropic and inotropic effects of vasoactive intestinal peptide,
      VIP, were studied in an isolated canine right atrial preparation. Atria were
      removed, maintained in a bath, and perfused with Tyrode's solution. Contractile
      force and atrial depolarization were measured. VIP (18.8-600 pmol) was injected
      into a cannulated sinoatrial nodal artery and dose response curves were obtained.
      The mean EC50 was similar for the inotropic and the chronotropic responses (136
      and 144 pmol, respectively). Time courses of the onset and of recovery from the
      responses were measured. Times for onset of VIP effects were similar but, once
      the effect was initiated, rate of development of the response and recovery time
      from the responses were dose dependent. The increases in atrial rate lasted two
      to four times longer than did the increases in contractile force. Recovery from
      the chronotropic and inotropic responses to VIP differ, suggesting that the
      intracellular responses are coupled differently to the receptors. The responses
      to VIP were compared to those of 100 pmol isoproterenol, another positive
      chronotropic and inotropic agent. Isoproterenol was a slightly more potent
      chronotropic and inotropic agent than VIP. Desensitization of the responses was
      determined. Repeated exposures to VIP decreased the chronotropic response but not
      the inotropic response to VIP. There was no significant decrease in
      responsiveness to isoproterenol.

PMID- 8988484
TI  - Effects of locally administered desipramine on myocardial interstitial
      norepinephrine levels.
AB  - We investigated whether locally administered neuronal uptake blockade with
      desipramine (DMI) modified basal myocardial interstitial norepinephrine (NE)
      levels and stimulation-induced NE responses. Using the dialysis technique,
      dialysates were sampled from the midwall of the left ventricle in anesthetized
      cats. Dialysate NE concentrations, as an index of myocardial interstitial NE
      level, were measured by high performance liquid chromatography. Through the
      dialysis probe, local administration of DMI (10(-4) mol/l) increased the
      dialysate NE level from 24.6 +/- 12.2 to 127.8 +/- 37.4 and from 11.9 +/- 5.4 to
      64.9 +/- 28.7 pg/ml regardless of whether stellate ganglia were intact or
      transected. The arterial pressure and heart rate responses to electrical
      stimulation of the stellate ganglia were not altered by DMI. Control nerve
      stimulation increased dialysate NE concentrations to 214.5 +/- 100.0 and 57.5 +/-
      22.0 pg/ml at 5 Hz and 2 Hz, respectively. During local administration of DMI,
      nerve stimulation-induced NE response increased to 997.5 +/- 202.0 at 5 Hz and to
      436.0 +/- 68.5 pg/ml at 2 Hz. We conclude that local administration of DMI caused
      marked rises in basal myocardial interstitial NE concentrations and responses to
      cardiac sympathetic activation.

PMID- 8988485
TI  - Modulation of noradrenaline release from isolated human atrial appendages.
AB  - Prejunctional modulation of noradrenaline release has been studied extensively in
      various experimental preparations. However, the presence and importance of
      prejunctional noradrenaline release modulation in human cardiac tissue is still
      unclear. In this study, we have used superfused human right atrial appendages
      excised from patients undergoing open heart surgery. The tissues were cut into
      six pieces and incubated with [3H]noradrenaline (4 microCi/ml. 0.2 microM) for 30
      min at 37 degrees C. The tissues were then inserted into a suprafusion system and
      washed for 75 min with a Krebs-Henseleit solution at a rate of 0.4 ml/min. The
      experimental protocol consisted of a 60-min perfusion period during which a field
      stimulation (2 ms pulses, 60 s. 50 mA, 5 Hz) was delivered at 10 and 45 min. The
      effect of the drugs on the stimulation-induced outflow of radioactivity was
      determined by adding them 20 min before the second stimulation. Each experiment
      was carried out with or without desipramine (1 microM) to study the influence of
      the reuptake blockade. Fenoterol (1-1000 nM), a beta 2-adrenoceptor agonist, and
      angiotensin II (1-1000 nM) significantly increased noradrenaline release in a
      concentration-dependent manner. The administration of arecaidine propargyl ester
      (0.03-3 microM), a non-specific muscarinic receptor agonist, and
      propylnorapomorphine (0.1 nM-1 microM), a DA2-dopaminergic agonist, produced a
      concentration-dependent inhibition of the stimulation-induced outflow of
      radioactivity. The alpha 2-adrenoceptor agonist, oxymetazoline (1 microM)
      inhibited noradrenaline release at a stimulation frequency of 2 Hz, but not at 5
      and 10 Hz. The alpha 2-adrenoceptor antagonist, idazoxan (1 microM),
      significantly increased the release of noradrenaline at 2 and 5 Hz but not at 10
      Hz. The results obtained in the present study demonstrated the presence of the
      facilitatory beta 2-adrenoceptor and angiotensin II receptor as well as the
      presence of inhibitory alpha 2-adrenoceptor, muscarinic and DA2-dopamine
      receptors in the human atrial appendage.

PMID- 8988486
TI  - The discharge behaviour of single sympathetic neurones supplying human sweat
      glands.
AB  - Firing properties of single sudomotor axons were studied via tungsten
      microelectrodes inserted percutaneously into cutaneous fascicles of the peroneal
      nerve in awake subjects. Sweating was induced by radiant heat and measured by
      changes in skin electrical resistance within the innervation territory on the
      dorsum of the foot. Eight units were classified as sudomotor neurones because
      spike-triggered averaging revealed a time-locked relationship between the unitary
      discharge and the subsequent decrease in skin resistance (1.12 +/- 0.05 s), but
      no relationship to skin blood flow (measured by a laser-doppler probe). Sudomotor
      units usually fired only one (maximum six) spike(s) in a sympathetic burst. The
      mean firing rate was 0.62 Hz, but instantaneous frequencies above 50 Hz could be
      generated. R-wave triggered histograms and coherence analysis revealed
      significant coupling between the firing of three sudomotor neurones and the ECG.
      Moreover, the firing of four sudomotor neurones showed a weak but significant
      correlation with the spontaneous fluctuations in cardiac interval, diastolic
      pressure, or the rate of fall in arterial pressure. We conclude that the
      discharge of human sudomotor neurones is modulated by baroreceptor input.

PMID- 8988487
TI  - The afferent discharges from sensors for interleukin 1 beta in the hepatoportal
      system in the anesthetized rat.
AB  - The effect of intraportal administrations of interleukin 1 beta (IL-1 beta) on
      the afferent activity of the hepatic branch of the vagus nerve was observed in
      urethane anesthetized rats. An intraportal injection of IL-1 beta in doses of 10
      pg and 100 pg per animal (300-400 g body wt.) resulted in dose-dependent increase
      in the afferent activity, which lasted about 70-100 min. Further, intraportal
      injection of IL-1 beta (100 pg) induced reflex activation of efferent activity of
      the splenic (sympathetic) nerve and vagal thymic nerve. This reflex activation
      was not observed in hepatic vagotomized rat and after an administration of the
      same dose of IL-1 beta into the systemic vein in normal rat. The results suggest
      the existence of sensors for IL-1 beta which send information on IL-1 beta in the
      portal venous blood to the central nervous system through the hepatic branch of
      the vagus nerve and play some role in reflex regulation of immune function.

PMID- 8988488
TI  - Effect of celiac ganglionectomy on tachykinin innervation, receptor distribution
      and intestinal responses in the rat.
AB  - Substance P (SP) is an important neurotransmitter in the control of intestinal
      motility and is found in both the enteric and sympathetic nervous systems. This
      study examined the effect of celiac ganglionectomy on (1) mechanical properties
      of the circular muscles of the duodenum, ileum and proximal colon, (2) circular
      muscle responses to SP and neurokinin A. (3) distribution of substance P-like
      immunoreactive nerves, and (4) the distribution of neurokinin 1 and neurokinin 2
      receptors. Celiac ganglionectomy resulted in an effective sympathectomy as
      evidenced by a marked decrease in norepinephrine content and tyrosine hydroxylase
      staining in the duodenum, ileum and proximal colon. The in vitro length/tension
      characteristics of the circular muscle of the duodenum, ileum and colon were
      unchanged after ganglionectomy. In all regions of the gut studied, substance P
      and neurokinin A caused dose-dependent contractions that were unaltered by celiac
      ganglionectomy. Immunohistochemistry revealed moderate substance P-like
      immunoreactive fibers in the myenteric plexus, submucosal plexus and circular
      muscle of the ileum, while in the colon, substance P-like immunoreactivity was
      intense in the myenteric plexus, and moderate in the circular muscle. In vitro
      autoradiography showed minimal binding of SP (NK1 receptor) or neurokinin A (NK2
      receptor) in the ileum and significantly greater binding in the circular muscle
      layer of the colon. Celiac ganglionectomy did not affect substance P-like
      immunoreactivity, or NK1 or NK2 receptor binding. A greater contractile response
      to neurokinins was seen in the colon than in the duodenum or ileum, which
      paralleled the receptor density. The studies demonstrate that surgical celiac
      ganglionectomy, unlike chemical sympathectomy, does not affect the substance P
      innervation, receptor density or physiological responses of the intestine. The
      greater contractile response of the colon than the ileum parallels the greater
      receptor density rather than the peptide content as determined by
      immunhistochemistry.

PMID- 8988489
TI  - Synaptic vesicle proteins in cells of the sympathoadrenal lineage.
AB  - The cells of sympathoadrenal lineage display different characteristics after
      differentiation, although they stem from the same neural crest precursor during
      embryonic development. In the present study we compared the distribution patterns
      of several synaptic vesicle proteins in the superior cervical ganglion (SCG) and
      the adrenal medulla. Using indirect immunofluorescence combined with confocal
      laser scanning microscopy, it was observed that antisera against integral
      synaptic vesicle membrane proteins (SV2, synaptotagmin I, synaptobrevin II and
      synaptophysin) induced strong immunoreactivities in these cells, but anti
      synaptobrevin I caused only a faint fluorescence. Immunoreactivities of the
      synaptic vesicle-associated proteins Rab3a and SNAP25 were also observed in the
      cells. Synapsin-Ia-reactive material appeared absent from chromaffin cells but
      present in small amounts in sympathetic neurons in the SCG and iris terminals. On
      the other hand, synapsin IIa immunoreactive material was strong in most SCG
      neurons and in adrenergic iris terminals. The neural specific clatrin light chain
      was detected in the SCG cells and in ganglion cells of the adrenal, but only weak
      traces could be observed in chromaffin cells. One of the vesicular monoamine
      transmitter transporters, VMAT2, which is expressed in catecholamine neurons in
      the brain stem, was observed in most cells in the SCG and also in groups of cells
      in the adrenal medulla, where the VMAT2-positive small chromaffin cells were PNMT
      negative. SIF cells in the SCG contained most of the synaptic vesicle proteins
      investigated. The results show that after differentiation, sympathetic neurons,
      SIF cells and adrenal chromaffin cells still share many vesicle proteins even
      though their physiology is different.

PMID- 8988490
TI  - Postural tachycardia syndrome: time frequency mapping.
AB  - Orthostatic tachycardia is common but its specificity remains uncertain. Our
      preliminary work suggested that using autonomic function testing in conjunction
      with time-frequency mapping (TFM), it might be possible to characterize a subset
      of the postural tachycardia syndrome (POTS), that is due to a restricted
      autonomic neuropathy. We describe 20 patients (17 women and 3 men, aged 14-43
      years) with florid POTS and 20 controls (14 women and 6 men, aged 20-41 years).
      Autonomic failure was quantified by its distribution (cardiovagal, adrenergic and
      sudomotor) and severity, a symptom profile was generated, and spectral indices,
      based on modified Wigner distribution during rest and head-up tilt (80 degrees)
      were evaluated. During tilt-up POTS patients differed from controls by an
      excessive heart rate (> 130 bpm) (P < 0.001), and higher diastolic pressure (P <
      0.01). During rest, cardiovagal oscillations (at respiratory frequencies [RF])
      and slow rhythms at nonrespiratory frequencies (NONRF) (from 0.01 to 0.07 Hz) in
      R-R intervals (RRI) (P < 0.01) were reduced. Both RF and NONRF rhythms in RRI
      were further blunted with tilt-up (P < 0.001). Slow adrenergic vasomotor rhythms
      in blood pressure (BP) (approximately 0.07 Hz) surged with tilt-up and returned
      to normal levels afterwards. The index of sympatho-vagal balance (NONRF-Systolic
      BP (SBP)/RF-RRI) was dramatically increased in POTS (P < 0.001). Distal
      postganglionic sudomotor failure was observed, and impairment of the BP responses
      to the Valsalva maneuver (phase II) suggested peripheral adrenergic dysfunction.
      Persistent orthostatic dizziness, tiredness, gastrointestinal symptoms and
      palpitations were common in POTS patients. It is possible to identify a subset of
      POTS patients who have a length-dependent autonomic neuropathy, affecting the
      peripheral adrenergic and cardiovagal fibers, with relative preservation of
      cardiac adrenergic fibers.

PMID- 8988491
TI  - Cells of origin of spinal projections from the paraventricular nucleus (PVN) of
      the hypothalamus in the chicken.
AB  - Hypothalamic neurons projecting to the lumbar (lumbar-neurons) and sacral (sacral
      neurons) segments were retrogradely labeled by injections of fluorescent axonal
      tracers (FITC-WGA, TRITC-WGA) into both the lumbar and sacral segments. Labeled
      neurons were distributed in the principal part of the paraventricular nucleus
      (PVN), but not in the pars dispersa of this nucleus. Of these neurons, some small
      and oval-shaped neurons (about 10 microns in diameter) in a middle part of the
      PVN were observed to be labeled by both FITC-WGA and TRITC-WGA (lumbosacral
      neurons) suggesting double projections to lumbar and sacral segments.

PMID- 8988492
TI  - For the children.

PMID- 8988493
TI  - The prognostic value of the Glasgow Coma Scale, hypoxia and computerised
      tomography in outcome prediction of pediatric head injury.
AB  - The outcome of 151 children less than 15 years of age and admitted within 24 h of
      head injury was studied in relation to clinical and computed tomography (CT) scan
      features. Thirty one (20.5%) had a poor outcome (24 died, 6 were severely
      disabled at 6 months after injury and 1 was in a persistent vegetative state)
      while 120 (79.5%) had a good outcome (89 recovered well and 31 were moderately
      disabled). Factors associated with a poor outcome were Glasgow Coma Scale (GCS)
      score 24 h following injury, presence of hypoxia on admission and CT scan
      features of subarachnoid haemorrhage, diffuse axonal injury and brain swelling.
      GCS scores alone, in the absence of other factors, had limited predictive value.
      The prognostic value of GCS scores < 8 was enhanced two-to fourfold by the
      presence of hypoxia. The additional presence of the CT scan features mentioned
      above markedly increased the probability of a poor outcome to > 0.8, modified
      only by the presence of GCS scores > 12. Correct predictions were made in 90.1%
      of patients, indicating that it is possible to estimate the severity of a
      patient's injury based on a small subset of clinical and radiological criteria
      that are readily available.

PMID- 8988494
TI  - Long-term outcome in infants with the shaking-impact syndrome.
AB  - Nonaccidental injury accounts for nearly one quarter of all hospital admissions
      for head injury in infancy, and is associated with significant morbidity and
      mortality. Long-term outcome in survivors, however, has been incompletely
      studied. In this series, 84 infants 2 years of age and younger with the shaking
      impact syndrome consecutively admitted to a single hospital between 1978 and 1988
      were identified. A questionnaire detailing current medical, developmental, and
      behavioral status was developed, and attempts were made to locate the 62 children
      surviving the acute injury. Family instability and strict confidentiality
      restrictions precluded locating the majority of children, but 14 children with
      demographic and injury characteristics similar to those of the overall group were
      contacted at an average of 9 years after injury. Seven children were severely
      disabled or vegetative, 2 were moderately disabled, and 5 had a good outcome. Of
      the latter group, 3 had repeated grades and/or required tutoring. Acute factors
      associated with poor outcome included unresponsiveness on admission, need for
      intubation, age less than 6 months, and bilateral or unilateral diffuse
      hypodensity on CT scan. All children with bilateral diffuse hypodensity and loss
      of gray-white differentiation on CT scan remained blind, retarded, nonverbal, and
      nonambulatory in spite of aggressive medical and surgical management. This study
      suggests that the majority of children surviving the shaking-impact syndrome
      suffer major permanent morbidity, and that acute factors predicting long-term
      outcome may help guide aggressiveness of care.

PMID- 8988495
TI  - Posterior fossa lateral ependymoma in childhood.
AB  - Over a period extending from 1984 to 1993, 16 children ranging in ages from 2
      months to 12 years with posterior fossa ependymoma were treated. Four of these
      tumors were classified as lateral ependymomas because of their configuration and
      suspected site of origin. These 4 patients' ages ranged from 2 months to 5 years.
      Signs and symptoms of increased intracranial pressure and cranial nerve
      dysfunction were the hallmark of their presentation. Their imaging evaluation
      included a preoperative and postoperative CT san and/or MRI. A gross total
      surgical resection' was completed in the 4 children. At least a 1-year follow-up
      was available for all the patients. Intraoperative brain stem evoked potentials
      and facial and glossopharyngeal nerve monitoring were used in all the surgeries.
      Three children required a ventriculoperitoneal shunt postoperatively.
      Chemotherapy was used postoperatively in 3 children. The 4th child did not
      receive chemotherapy due to parental refusal and succumbed to a recurrence 1
      years postoperatively. Radiation therapy was given to 2 children. Tumor
      recurrences developed in all children at 12 months, 18 months, 3 years and 4
      years postoperatively in proximity to the original tumor site. Histologic
      sections in 3 patients, including those at the time of recurrence, were
      consistent with a low mitotic index. Only 1 child's histologic diagnosis was
      consistent with a high-grade ependymoma. The lower cranial nerve dysfunction
      transiently worsened in all the patients and was permanent in 2. The child's age,
      tumor histology and extent of resection play an important role in the prognosis
      of posterior fossa ependymoma. The lateral posterior fossa ependymoma has a
      particularly poor prognosis due to its location and its significant postoperative
      morbidity. The authors propose a combined midline and lateral suboccipital
      approach in order to expose the fourth ventricular floor, upper cervical spine,
      lateral recess, cerebellomedullary fissure, cerebellopontine and the
      cerebellomedullary cistern in an attempt at a "total' resection with a focus on
      the site of origin. The usage of neurophysiological monitoring appears to be
      useful in limiting and predicting the extent of postoperative complications.
      However, prolonged morbidity is likely and is commonly related to lower cranial
      nerve deficits. The author proposes a proactive approach in order to limit the
      sequelae of these complications.

PMID- 8988496
TI  - Mixed neuronal-glial tumors (gangliogliomas) in children.
AB  - Mixed tumors account for about 10% of the childhood central nervous system
      tumors. Studies of the most common tumor, the ganglioglioma, in patients of all
      ages suggest that optimal therapy is total gross resection. There are few studies
      on these tumors in children. In our institution between 1984 and 1993, 28
      children with gangliogliomas (4 of which were anaplastic) and 4 children with
      dysembryoplastic neuroepithelial tumors were treated and followed. Fourteen had
      local subarachnoid involvement. Total gross resection was usually curative,
      regardless of histology. Subarachnoid involvement was not indicative of a poorer
      prognosis.

PMID- 8988497
TI  - Long-term follow-up after high-activity 125I brachytherapy for pediatric brain
      tumors.
AB  - A retrospective review including long-term follow-up (4.6-12.0 years) was
      performed of all 28 pediatric patients who underwent high-activity 125I
      brachytherapy at the University of California, San Francisco, for primary or
      recurrent brain tumors from 1980 until 1991. There were 4 glioblastomas, 11 high
      grade nonglioblastoma multiforme (NGM) malignant gliomas, 10 contrast-enhancing
      low-grade NGM, 2 choroid plexus carcinomas, and 1 rhabdomyosarcoma. The 13
      survivors included 7 of 8 patients with primary high-grade NGM, 2 of 3 patients
      with primary low-grade NGM, and 3 of 7 patients with recurrent low-grade NGM.
      Necrosis (with or without tumor) was identified in 17 of 22 reoperated patients.
      The mean Karnofsky performance status was 88 +/- 9 at the time of brachytherapy,
      87 +/- 7 at 3 years, and 87 +/- 9 in 11 patients alive at 6-12 years.
      Brachytherapy is a useful modality for treating selected pediatric brain tumors,
      and although focal necrosis is a common sequela, it does not tend to have a major
      impact on the Karnofsky performance status, if the implant site is amenable to
      reoperation.

PMID- 8988498
TI  - Fatal air bag mediated craniocervical trauma in a child.
AB  - This case report describes a 5-year-old child who sustained fatal craniocervical
      injuries as the result of an inflating automobile air bag. Although air bags have
      in general been shown to reduce the severity of injury to occupants of vehicles
      involved in front-end collisions, a growing number of incidents suggests that in
      some instances the air bag system itself may cause injuries, some of which can be
      serious or even fatal. Small children and infants in infant seats travelling in
      the front passenger seat appear to be particularly at risk. The increasing number
      of reports of air bag mediated injuries highlights the need for changes in both
      system design and possibly the threshold speed required for air bag deployment.

PMID- 8988499
TI  - Spinal epidural venous plexus: its MR enhancement patterns and their clinical
      significance.
AB  - OBJECTIVE: Evaluation of the clinical utility of enhancement of the spinal
      epidural venous plexus (SEVP) on postcontrast MR imaging. MATERIALS AND METHODS:
      The SEVP on pre- and postcontrast T1-weighted sagittal and axial MR images were
      evaluated in 188 patients whose MR findings were abnormal (positive group), in
      223 patients with normal MR (negative group), and in 35 volunteers. The
      enhancement patterns of the SEVP were graded 1 to 4 according to their degree of
      dilation. These three groups were compared and analyzed. RESULTS: Epidural and
      intradural lesions in the positive group showed higher grades of epidural vein
      enhancement compared with the negative group (p = 0.01). Epidural abscesses and
      epidural metastases frequently showed moderate to marked dilatation of the SEVP.
      Degenerative disk disease with stenosis of the spinal canal exhibited more
      localized patterns of dilation. Most intradural lesions with cord swelling
      demonstrated dilation of the SEVP. Visualization of the SEVP did not differ
      statistically between bone and soft tissue lesions in the positive group and the
      negative group (p = 0.13). Evaluation of follow-up examinations showed that
      changes in SEVP grades were indicative of changes in disease. CONCLUSION: SEVP
      enhancement patterns assist in the evaluation of disease in the spinal canal and
      will help to differentiate normal from pathological conditions.

PMID- 8988500
TI  - Intra-arterial digital subtraction angiography with extra-large fields using a
      computed radiography system in evaluating peripheral vascular disease.
AB  - The authors evaluated the usefulness of intra-arterial digital subtraction
      angiography (DSA) with extra-large field sizes using a computed radiography (CR)
      system in evaluating peripheral vascular disease (PVD). Intra-arterial DSA using
      CR was performed in 55 patients with suspected PVD. A 4 F catheter was advanced
      into the abdominal aorta via the transbrachial approach and 90 ml of contrast
      medium was injected during six exposures using a long leg changer mounting a
      total of 18 imaging plates on six surfaces. Visualization of the superficial
      femoral and popliteal arteries was judged as diagnostic in all cases. The
      abdominal aorta, iliac arteries, and subtrifurcation were also visualized in most
      cases, but visualization was suboptimal in some cases. As a complication, median
      nerve palsy occurred in one case. This technique is thought to be a useful method
      for evaluating PVD because of the advantages of a large field of view and wide
      exposure latitude, in spite of its relatively long processing time.

PMID- 8988501
TI  - MR imaging of idiopathic trigeminal neuralgia: correlation with non-surgical
      therapy.
AB  - Magnetic resonance (MR) findings in patients with idiopathic trigeminal neuralgia
      were evaluated and correlated with the effectiveness of non-surgical treatments.
      Thirty-four patients with idiopathic trigeminal neuralgia (ITN) were examined
      using T1- and T2-weighted spin-echo (SE) pulse sequence techniques to evaluate
      their trigeminal root-entry zones and the vessels contacted prior to non-surgical
      treatment (retrogasserian glycerol injection, peripheral nerve block, or only
      oral analgesics). Vascular contact at the proximal portion of the preganglionic
      segment (PGS) of the trigeminal nerve and deformity of the PGS on the affected
      side were observed in 97% and 47% of the patients, respectively. Non-surgical
      treatments were curative in 12 (67%) but failed in two (11%) of the 18 patients
      without deformed PGS. However, among 16 patients with deformed PGS, they were
      curative in only six (37.5%) and failed in four (25%). Results of this study
      suggest that MR imaging could be useful in the clinical assessment of trigeminal
      neuralgia prior to instituting non-surgical treatment.

PMID- 8988502
TI  - Prevalence of vertebral artery dissection in Wallenberg syndrome:
      neuroradiological analysis of 93 patients in the Tohoku District, Japan.
AB  - To assess the prevalence of vertebral artery dissection in Wallenberg syndrome
      (lateral medullary syndrome), records of 93 patients (70 men, 21 women, and 2
      patients not identified by gender; mean age at ictus, 58.1 years) with symptoms
      of Wallenberg syndrome who underwent MRI and/or vertebral angiography were
      reviewed retrospectively. Study items included the following: (A) headache; (B)
      arterial intramural hematoma on T1-weighted images as an MR finding; and (C)
      double lumen, intimal flap, pearl and string sign, and string sign as
      angiographic findings. These abnormal findings suggesting vertebral artery
      dissection were scored as 1 or 2 points. According to his or her total score,
      each patient was classified as "definite dissection." "probable dissection,"
      "suspected dissection," or "no dissection." Twenty-three of 93 patients were
      classified as "definite dissection," 23 as "probable dissection," 27 as
      "suspected dissection," and 20 as "no dissection." The frequency of definite or
      probable dissection in Wallenberg syndrome was estimated at 50% or more. Thus,
      vertebral artery dissection is a frequent cause of Wallenberg syndrome.

PMID- 8988503
TI  - Renal cortical retention of contrast medium after angiography as assessed by
      delayed CT: a multivariate analysis.
AB  - Renal cortical retention (RCR) of contrast medium discovered by delayed X-ray
      examination is sometimes reported in patients with problems in the urinary
      system. However, we frequently found RCR even in patients with normal renal
      function. Therefore, we examined the incidence and factors involved in RCR by
      delayed computed tomography (CT) 12-24 hours after angiography in 168 patients.
      RCR was found in 80 of 168 cases (48%). Ioxaglate (60%) and iohexol (60%) showed
      higher incidences of RCR than diatrizoate (37%) and iopamidol (37%). Multivariate
      logistic regression analysis was performed to determine the predisposing factors
      of RCR. Dose of administered contrast medium by body weight (p = 0.004), age (p =
      0.009), sex (p = 0.013), type of contrast medium (p = 0.003), serum albumin (p =
      0.011), and serum creatinine (p = 0.002) were identified as significant and
      independent predisposing factors of RCR. We suggest that RCR is not a rare
      phenomenon if delayed CT is carried out.

PMID- 8988504
TI  - Functional evaluation of transplanted kidneys by Gd-DTPA enhanced turbo FLASH MR
      imaging.
AB  - We evaluated the usefulness of dynamic turbo FLASH MR imaging in the differential
      diagnosis of complications after renal transplantation in 17 patients (10 from
      living relatives and 7 from cadavers). Coronal turbo FLASH dynamic images were
      obtained every 5 sec for 5 min after an intravenous bolus injection of Gd-DTPA.
      Corticomedullary differentiation (CMD) on spin echo coronal T1-weighted images
      and MR renogram patterns of the renal cortex and medulla were obtained for
      quantitative analysis of the Gd-DTPA-enhanced dynamic turbo-FLASH images. The
      signal intensity ratio of the medulla to cortex after Gd-DTPA enhancement was
      compared among four groups: normal (n = 9), acute tubular necrosis (ATN) or
      cyclosporine A (CyA) tubulopathy (n = 6), acute rejection (AR) in the living
      related donor kidney (n = 4), and AR in the cadaveric kidney (n = 5). Although
      loss of CMD was seen in severe renal dysfunction in the transplanted kidneys,
      there was considerable overlap among the four groups. On dynamic study, there was
      significant differences in the signal intensity ratio of the medulla to cortex
      between normally functioning kidneys or ATN/CyA tubulopathy and AR (p < 0.01). In
      patients with severe renal dysfunction, the arterial cortical peak was
      indistinct. In conclusion, MR renograms obtained from dynamic turbo FLASH MR
      imaging played a significant role in evaluating dysfunction of the renal
      transplant.

PMID- 8988505
TI  - Human melanoma treated by boron neutron capture therapy: comparison of the
      clinical response with the predicted response.
AB  - PURPOSE: A patient with malignant melanoma on the left foot was treated by
      thermal neutron capture therapy using 10B-paraboronophenylalanine. We compared
      the actual (clinical) response with the predicted response estimated using our
      past experimental and clinical data, and discussed some problems to be overcome
      in the future. MATERIALS AND METHODS: We adopted an intravenous drip infusion of
      the compound whereby 170 mg/kg of the drug was administered over 4-5 hours before
      neutron irradiation. The patient was then irradiated with thermal neutrons from
      the Musashi Reactor at a reactor power of 100 kW and a neutron flux of 1.0 x
      10(9) n/cm2/s at the collimator surface. The total absorbed dose to the melanoma
      and the surrounding skin was calculated by multiplying the thermal neutron
      fluences by the conversion factor. RESULTS: The total absorbed doses to the
      melanoma and the surrounding normal skin were calculated as 19.0 and 9.4 Gy,
      respectively. These absorbed doses were estimated at 33.5 and 14.2 RBE-Gy,
      respectively, assuming that the relative biological effectiveness (RBE) of the
      high LET radiations was 2.0 and that each component of the mixed radiation was
      simply additive. The melanoma showed marked regression with mild skin reaction
      (dry desquamation) a month after therapy, and finally disappeared 10 months after
      therapy. There were no no substantial side effects. CONCLUSION: We concluded that
      the outcome of our calculated dose values agreed well with the clinical response
      and that their compatibility indicated considerable validity for our approach.
      However, there are still some problems-uncertainty concerning the 10B
      concentration in tumor and skin, determination of the total absorbed dose, and a
      single curative dose for malignant melanoma-to be overcome with regard to
      clinical use of this therapy.

PMID- 8988506
TI  - Clinical evaluation of gamma knife radiosurgery for intracranial arteriovenous
      malformation.
AB  - PURPOSE: Aim of the study is to compare our treatment results or gamma knife
      radiosurgery for arteriovenous malformation (AVM) and to obtain factors
      determining nidus obliteration and/or adverse effect. METHODS: We analyzed 236
      patients with AVM treated between June 1990 and February 1994. The patients
      consisted of 137 men and 99 women, and ranged in age from 4 to 71 years. AVM
      volume ranged 0.7 to 37.7 ml. Maximum and peripheral doses ranged from 18.2 to
      60.0 Gy and 10.0 to 28.0 Gy, respectively. RESULTS: Complete obliteration rates
      at 1,2, and 3 years were 36.2, 68.9, and 86.6%, respectively. The mean time to
      complete obliteration was 21.4 months. Univariated analysis revealed that
      calculated target volume, peripheral dose, peripheral percent dose and treatment
      optimality were significant factors for complete obliteration. In multivariate
      analysis, calculated target volume, treatment optimality, and CT-based planning
      were significant factors. The actuarial risk of post-radiosurgical brain edema at
      2 years was 20.0%. In both univariate and multivariate analysis, calculated
      target volume was the only significant factor. Symptomatic complications
      developed in 10.0% of patients at 2 years, but no significant factors were
      identified. Permanent complications and severe neurological deficits were seen in
      4.4 and 2.8% of patients, respectively. CONCLUSIONS: Our results were similar to
      those reported previously. Accurate CT-based planning contributed to an improved
      obliteration rate.

PMID- 8988507
TI  - Radiologic manifestation of spinal accessory neurinoma: a case report.
AB  - Spinal accessory nerve neurinoma is very rare; only 12 cases have been reported
      in the literature. We describe a 54-year-old woman who had a cisterna magna tumor
      expanding extracranially to the C1 cervical body. The tumor originated from the
      spinal root of the right accessory nerve. The radiological features including CT,
      MRI, and angiography are discussed. There have been reports on cranial MRI
      studies of spinal accessory neurinoma. MRI suggested an extra-axial tumor. The
      histological diagnosis was mixed Antoni A and B neurinoma. The neuroradiological
      findings of 12 cases of neurinoma of the accessory nerve reported in the
      literature are reviewed.

PMID- 8988508
TI  - Case report: MR appearance of hemangiopericytoma of the thigh.
AB  - We report a case of hemangiopericytoma in the thigh of a 42-year-old woman. CT
      examination depicted a peripherally enhanced, multicystic mass without
      calcification. On T1-weighted images of MRI, the mass showed slightly high signal
      intensity relative to muscle, with the exception of the lower pole, which showed
      high signal intensity. On T2*-weighted images, the mass showed high signal
      intensity and cystic appearance. The lower pole showed low signal intensity on
      T2*-weighted images and was thought to be intratumoral hemorrhage. Low signal
      intensity structures on both T1- and T2*-weighted images were observed within and
      around the mass. They were thought to be dilated vessels, although this was not
      confirmed at surgery. Hemangiopericytoma should be considered in the differential
      diagnosis of a tumor in the thigh when MR images show the mass with slightly high
      signal intensity on T1-weighted images, intratumoral hemorrhage, and flow voids
      within or adjacent to the tumor.

PMID- 8988509
TI  - Influence of immediate post-therapy bone scintigraphy in the assessment of
      response to therapy in a case of nasopharyngeal carcinoma.
AB  - A patient with undifferentiated stage IV (T3N3M0) nasopharyngeal carcinoma (WHO
      type III) underwent pre- and one-month post-therapy bone scintigraphy as part of
      an ongoing trial combining scintigraphic and radiographic modalities. The patient
      had advanced disease in the nasopharynx and bulky cervical lymph nodes at
      presentation. Initial bone scintigraphy performed 10 days prior to therapy was
      negative for bone metastases. Immediately after concomitant chemoradiotherapy,
      bone scintigraphy revealed distant metastases, whereas clinical assessment of
      disease disclosed complete response to therapy in the nasopharynx and cervical
      lymph nodes. The scintigraphic findings were also confirmed by a subsequent MRI
      scan of the corresponding regions.

PMID- 8988510
TI  - Unusual pulmonary metastasis of neuroblastoma: a case report.
AB  - A case of unusual pulmonary metastasis of neuroblastoma in an 8-year-old girl is
      presented. Nodular opacities mimicking pulmonary tuberculosis first appeared in
      lung apices on chest radiographs. They subsequently developed into extensive
      consolidations with mediastinal involvement. Metastasis of neuroblastoma was
      confirmed at autopsy.

PMID- 8988511
TI  - Adult cystic Wilms' tumor (nephroblastoma): radiologic features with pathologic
      correlation.
AB  - Wilms' tumor is an uncommon disease in adults. Wilms' tumor typically presents as
      a large complex mass with cystic component and varying degrees of vascularity.
      The previously reported radiologic findings have reflected this complex
      appearance. We present a case of cystic Wilms' tumor in an adult patient. The
      tumor presented as a large, rapidly growing, hypovascular, multicystic mass with
      minimal solid component which showed as septation on ultrasound, contrast
      enhanced CT, and MR studies. The preoperative findings were suggestive of
      multilocular cystic nephroma. We suggest that Wilms' tumor should be included in
      the differential diagnosis of a patient who presents with a large, rapidly
      growing, multicystic renal mass.

PMID- 8988512
TI  - Comparison of multileaf collimation and shield alloy blocks on an irregular
      target volume.
AB  - Multileaf collimation (MLC) is a crucial component dynamic conformal radiotherapy
      and can be used as a replacement for conventional blocks. The most appropriate
      volumetric approach for the lesion's shape is achieved by MLC by conforming the
      prescribed dose to the critical structure or normal tissue dose. In this study,
      the edge effects of dose profiles on an irregular radiation field obtained by MLC
      and shield alloy blocks drawn by a water-phantom system were compared. We used a
      SL25 linac machine with MLC consisting of 40 pairs of opposing leaves and
      conventional alloy block shielding on a water phantom system. We found no
      significant edge effect difference between MLC and conventional shielding, but
      MLC showed clear advantages over conventional blocks in terms of time-saving,
      repeatability, and reliability.

PMID- 8988513
TI  - Expression of IGF-I, IGF-I receptor and IGF binding proteins-1, -2, -3, -4 and -5
      in human atherectomy specimens.
AB  - The molecular and cellular processes that induce rapid atherosclerotic plaque
      progression in patients with unstable angina and initiate restenosis following
      coronary interventional procedures are uncertain. We examined primary (de novo)
      and restenotic lesions retrieved at the time of directional coronary atherectomy
      for expression of insulin-like-growth factor-I (IGF-I). IGF-I receptor, and five
      IGF binding proteins (IGFBPs), IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-5 in
      smooth muscle cells (SMCs) using colloidal gold immunocytochemistry. IGF-1, its
      receptor and binding proteins were not detected in SMCs of normal coronary
      arteries. IGF-I localized primarily in synthetic smooth muscle cells (sSMCs) in
      both de novo and restenotic plaques. IGF-I receptor localized on sSMCs and their
      processes and colocalized with IGF-I. Although morphometric analysis of IGF-I and
      IGF-I receptor immunoreactivity in sSMCs of de novo and restenotic lesions showed
      comparable levels of IGF-I (3.2 +/- 1.0 and 2.9 +/- 0.9, respectively). IGF-I
      receptor was significantly higher in de novo lesions as compared to restenotic
      lesions (10.7 +/- 2.5 and 4.2 +/- 1.3, P < 0.05, respectively). IGFBP-1, IGFBP-2,
      IGFBP-3, IGFBP-4 and IGFBP-5 localized in the cytoplasm of sSMCs and in the
      extracellular matrix. Quantitative reverse transcription polymerase chain
      reaction (QRT-PCR) performed on de novo atherectomy specimens identified mRNA for
      IGF-I, IGF-I receptor, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5 levels and detected
      mRNA for IGFBP-3. The expression of IGF-I, IGF-I receptor, and IGFBPs in
      atherectomy plaques suggests that the development of coronary obstructive lesions
      may be a result of changes in the IGF system.

PMID- 8988514
TI  - Canine prosomatostatin: isolation of a cDNA, regulation of gene expression, and
      characterization of post-translational processing intermediates.
AB  - Somatostatin is a tetradecapeptide (SS-14) initially isolated from the
      hypothalamus that is also found in D cells of the stomach and pancreas where it
      exerts an inhibitory action on a variety of gastrointestinal functions. Since
      many of concepts important to an understanding of gastrointestinal physiology are
      derived from experiments in the dog we examined somatostatin gene expression and
      post-translational processing in the canine fundus, antrum and pancreas. The
      canine somatostatin cDNA which is highly homologous to other known mammalian
      somatostatins was used to examine somatostatin expression in isolated canine
      fundic D-cells. Somatostatin expression induced by cholecystokinin (10(-8) M) was
      inhibited by the somatostatin analog, octreotide (10(-7) M). To examine
      somatostatin processing in the canine gut we noted that synthesis of SS-14 and
      somatostatin octacosapeptide (SS-28) involves endoproteolytic cleavage of
      prosomatostatin (proSS) at both paired and single basic amino-acid residues,
      respectively. Antisera capable of recognizing the amino-terminal residues of SS
      28, SS-28(1-14) and SS-28(1-12) were characterized and identified concentrations
      of SS-28(1-12) but not SS-28(1-14) in the fundus, antrum and pancreas equivalent
      to those of SS-14. Since previous biosynthetic studies in canine fundic D-cells
      showed that SS-14 was synthesized without the appearance of a SS-28 intermediate,
      we hypothesize that proSS is sequentially cleaved at a dibasic site to produce SS
      14 followed by monobasic cleavage that results in the formation of SS-28(1-12).
      Furthermore, equivalent amounts of SS-14 and SS-28(1-12) were co-released from
      canine fundic D-cells by CCK (10(-8) M) suggesting that the generation of these
      products occurs within the same regulated pathway of secretion.

PMID- 8988515
TI  - The effect of galanin and galanin fragments on blood pressure in the Cane toad,
      Bufo marinus.
AB  - Galanin has previously been shown to have a slight vasodepressor or no effect on
      blood pressure in placental mammals, but causes potent increases in blood
      pressure in several other vertebrate species. In this paper, the part of the
      galanin molecule responsible for the pressor activity was investigated in the
      Cane road, Bufo marinus by administration of fragments of galanin into
      anaesthetised toads and isolated arterial segments in an organ bath. In
      anaesthetised toads, the order of efficacy was human galanin > porcine galanin >
      Gal 1-16 > Gal 1-15 > Gal 3-15 > Gal 21-29 = 0. In isolated vessels, the first
      three peptides were equally effective. When four fragments of human galanin were
      tested in anaesthetised toads, the order of efficacy was human galanin > Gal 1-15
      > Gal 5-20 > Gal 10-25 > Gal 15-30. The substitution of alanine for tryptophan at
      position 2 or for tyrosine at position 9 abolished the pressor response to the
      human galanin fragment 1-18 in anaesthetised toads. These results suggest that
      vascular activity in the toad is retained within the N-terminus and that
      positions 2 (tryptophan) and 9 (tyrosine) are key amino acids in retention of the
      vascular activity of galanin.

PMID- 8988516
TI  - Effect of three galanin antagonists on the pressor response to galanin in the
      Cane toad, Bufo marinus.
AB  - Galanin is a neuropeptide that causes a marked pressor response in several non
      mammalian vertebrate species, and some marsupials. In this study, the effect of
      three galanin antagonists were tested on the pressor response to an intravenous
      dose (6.3 nmol/kg) of porcine galanin in anaesthetised Cane toads, Bufo marinus.
      Antagonists were injected at either 20 or 50 times the molar dose (x MD) of
      galanin. The antagonist, C7 (Galanin 1-13-spantide) reduced the pressor effect of
      galanin by 32.2 +/- 6.0% when delivered at 20 x MD (n = 4) and by 42.9 +/- 15.7%
      when delivered at 50 x MD (n = 4) of galanin, the response recovering within 30
      min. A second antagonist, M32a (Galanin 1-13-NPY 24-36) had no effect on the
      pressor response to galanin at 20 x MD (n = 4), but significantly reduced the
      pressor effect by 54.8 +/- 6.4% at 50 x MD (n = 5), which also recovered within
      30 min. Administration of a third antagonist, galantide or M15 (Galanin 1-13
      Substance P5-11), resulted in a profound drop in blood pressure, and did not
      affect the response to galanin at either dose. In conclusion, C7 and M32a are
      effective, short-term antagonists of the blood pressure effects of galanin in the
      toad.

PMID- 8988518
TI  - The effects of chronic administration of epidermal growth factor (EGF) to rats on
      the levels of endogenous EGF in the submandibular glands and kidneys.
AB  - Epidermal growth factor (EGF) is mainly produced in the submandibular glands
      (SMG) and in the kidneys. It has recently been reported that EGF-related ligands
      may induce their own biosynthesis (autoinduction) in vitro. In the present paper,
      we investigated whether chronic systemic treatment with EGF influenced the amount
      of endogenous EGF in the SMG and kidneys. Eight-week-old female Wistar rats were
      treated with subcutaneous injections of placebo (n = 16) or human recombinant EGF
      (150 micrograms/kg per day, n = 8) for 4 weeks. Urine was sampled the last 24 h
      of the study period. At the time of killing, the SMG and the kidneys were
      removed. The SMG was larger in the EGF-treated animals, 229.8 +/- 35.5 (mean +/-
      SD) mg than in the control animals, 181.7 +/- 18.1 mg (P < 0.01). The total EGF
      content was smaller (0.51 +/- 0.15 vs. 1.12 +/- 0.40 nmol EGF/SMG, P < 0.001).
      The kidneys were larger in the EGF-treated animals (1.38 +/- 0.08 vs. 1.28 +/-
      0.08 g, P < 0.05), but the EGF content and urinary excretions were not changed.
      In conclusion, chronic systemic treatment with EGF causes growth of the SMG with
      concomitantly reduced contents of EGF, and growth of the kidneys with unchanged
      content and excretion of EGF. These findings suggest that EGF may play a part in
      the regulation of the growth of the SMG and in EGF biosynthesis.

PMID- 8988517
TI  - Direct and modulatory effects of FMRFamide, SKPYMRFamide and acety1-SKPYMRFamide
      on LPa2, LPa3, and RPa3 identified neurons of Helix lucorum.
AB  - Three neuroactive peptides with an RFamide carboxyl terminal, one a tetrapeptide,
      FMRFamide, and two heptapeptides, SKPYMRFamide and acetyl-SKPYMRFamide, evoke
      direct and modulatory effects on identified neurons from left (LPa2, LPa3) and
      right (RPa3) parietal ganglia of the land snail. Helix lucorum. Local application
      of tetrapeptide and heptapeptides induce hyperpolarization or outward current
      when neurons are clamped at the resting potential. The reversal potential of
      these direct responses is near the potassium equilibrium potential. All
      investigated FMRFamide-related peptides reduce reversibly the inward current to
      local acetylcholine (ACh) application onto the neuron soma. Threshold
      concentrations of peptides for an inhibitory action on ACh-induced current are
      0.5-1.0 microM, ID50 = 0.7-1.2 microM, SKPYMRFamide evokes parallel shift to
      right of ACh dose-response curves increasing the ED50 for ACh but without
      changing the Hill number. SKPYMRFamide does not change the reversal potential of
      the ACh-induced inward current. It was concluded that SKPYMRFamide reduces the
      affinity of ACh for ACh receptor without a change in the number of ligand-binding
      sites per ACh receptor molecule. FMRFamide-related peptides can reduce the
      affinity of ACh for cholinergic receptors through inhibition of the molecular
      mechanism connecting the ACh receptor with its ion channels.

PMID- 8988519
TI  - Effects of interleukin-1 beta fragment (163-171) on progesterone and estradiol-17
      beta release by bovine granulosa cells from different size follicles.
AB  - Recent studies indicate that interleukin-1 beta may play a role in ovarian
      function. To explore this possibility, we examined the effects of a fragment of
      interleukin-1 beta (163-171 aa) on progesterone and estradiol-17 beta production
      by bovine granulosa cells from small (< 5 mm) and large (> 8 mm) follicles; in
      addition we investigated the distribution of monocytes/macrophages, a possible
      source of interleukin-1 beta in the follicles, to determine a possible
      relationship between production of the cytokine and its activity. Bovine
      follicles were divided according to the size, granulosa cells were obtained by
      aspiration and plated at a density of 10(5) cells/well; then different
      concentrations of interleukin-1 beta fragment (0, 0.5, 5, 20 ng/ml) with or
      without bFSH were added for 24 h. Progesterone (P4) and estradiol-17 beta (E2)
      concentrations in media were evaluated by validated RIAs. Interleukin-1 beta (0.5
      and 5 ng/ml) stimulated (P < 0.05) P4 output in both small and large follicles,
      while FSH-induced P4 output was reduced (P < 0.05) in large but not in small
      follicles by all the concentrations of peptide. FSH-induced E2 output was reduced
      (P < 0.05) in large, but not in small follicles. Immunohisto- and cytochemistry
      revealed a higher number of monocytes/macrophages in large follicles. It appears
      from our data that: (1) interleukin-1 beta fragment may modulate steroidogenesis
      in bovine granulosa cells depending on the stage of development of the follicle,
      and (2) the presence of monocytes/macrophages is related to this modulation.

PMID- 8988520
TI  - Isolation and characterization of schistostatin-2(11-18) from the desert locust,
      Schistocerca gregaria: a truncated analog of schistostatin-2.
AB  - An octapeptide was isolated from 7000 brains of the desert locust. Schistocerca
      gregaria by screening of HPLC fractions using a RIA for Dip-AST-2 (allatostatin-2
      from the cockroach). Maldi-TOF-MS revealed a mass of 921.4 Da. The primary
      structure of the peptide is LPVYNFGL-NH2. It is identical to the C-terminal
      portion of schistostatin-2 from Schistocerca gregaria. Therefore, it was
      designated Scg-AST-2(11-18). The chromatographic properties of the synthetic
      peptide are identical to these of the native peptide. The peptide is a truncated
      product of Scg-AST-2, suggesting that an endopeptidase which cleaves between Arg
      and Leu is present in the brain complex of S. gregaria. Although, Scg-AST-2(11
      18) contains the same C-terminus as Dip-AST-2, it has no inhibitory activity on
      the corpora allata (CA) of 2-day-old virgin females of D. punctata. This suggests
      that Scg-AST2 (11-18) may be the result of a proteolytic inactivation mechanism
      and/or that it may be involved in stage-dependent down regulation of allatostatic
      activity. To our knowledge, Scg-AST-2 is the first isolated peptide which has the
      active core of the allatostatin peptide family but nevertheless shows no activity
      in this bioassay.

PMID- 8988522
TI  - In the trout, CRH and AVT synergize to stimulate ACTH release.
AB  - Anterior pituitaries of the rainbow trout (Oncorhynchus mykiss) were incubated
      with graded concentrations of arginine vasotocin (AVT) or synthetic rat
      corticotrophin-releasing hormone (rCRH-41), alone or in combination, and the ACTH
      secreted into the medium was measured by a sensitive cytochemical bioassay. The
      aim was to determine the relative potencies of the two secretogogues and whether,
      in this fish species, they act synergistically. Rat CRF-41 and AVT both produced
      concentration-dependent increases in ACTH release. The minimum effective
      concentration for both peptides was approximately 1 nM but, at higher
      concentrations, the efficacy of CRF-41 was greater than that of AVT. Clear
      evidence of synergy between the two peptides was obtained. The response of the
      trout thus falls in line with observations in mammals and contrasts with findings
      for the goldfish.

PMID- 8988521
TI  - Postprandial glucose-dependent insulinotropic polypeptide and insulin responses
      in patients with chronic pancreatitis with and without secondary diabetes.
AB  - OBJECTIVE: To study GIP and insulin release after a test meal in patients with
      chronic pancreatitis with and without secondary diabetes mellitus. METHODS: 28
      patients with chronic pancreatitis were classified in groups I and II according
      to the presence or absence of secondary diabetes mellitus. Twelve healthy
      subjects were included as controls. After a test meal plasma GIP levels and serum
      insulin levels were determined at 0, 30, 60, 120 and 180 min. RESULTS: A
      significant diminished GIP response was found in the groups of patients with
      respect to the control group. No association could be detected with severity of
      pancreatic insufficiency. Higher values of GIP were demonstrated at 60 and 120
      min in patients without diabetes than in patients with it. CONCLUSIONS: An
      abnormal GIP response is present in cases of chronic pancreatitis irrespective of
      the presence or severity of pancreatic insufficiency. This response is further
      affected if secondary diabetes mellitus is present.

PMID- 8988523
TI  - Endothelin-1 and big endothelin-1 levels in normal term pregnancy and in
      preeclampsia.
AB  - To study the concentrations of endothelin-1 (ET-1) and its precursor, big ET-1,
      in samples of amniotic fluid, fetal urine, umbilical arterial and venous blood,
      retroplacental blood and maternal uterine and brachial venous blood obtained from
      normal and preeclamptic women. Samples were collected from 31 healthy pregnant
      women (16 in labor and 15 undergoing elective cesarean section) and 35
      preeclamptic women (9 in labor and 26 undergoing cesarean section). Big ET-1 and
      ET-1 were measured by radioimmunoassay and the ET-1 to big ET-1 ratios were
      calculated. In preeclamptic women there was a significant elevation of ET-1 in
      the maternal brachial and uterine veins and of big-ET-1 in the brachial vein. The
      ET-1 concentrations and the ET-1/big ET ratios were significantly higher on the
      fetal side (i.e., in the umbilical vein and amniotic fluid) than in maternal
      blood, but in these sampling locations there was no difference between the normal
      pregnancy and preeclampsia group. A significant negative correlation (r = -0.67,
      P < 0.01) was found between plasma ET-1 in the umbilical vein and birth weight in
      the preeclamptic group. ET-1 was significantly higher in amniotic fluid than in
      the first neonatal urine of corresponding pregnancies (15.0 +/- 2.0 vs. 3.0 +/-
      2.9 pmol/l, P < 0.05). The ET-1 and big ET-1 concentrations are significantly
      higher in fetal plasma and amniotic fluid than in maternal plasma, indicating
      increased endothelin converting enzyme activity and increased ET-1 production in
      utero. The elevated ET-1 concentration in maternal blood in preeclamptic compared
      with normal pregnant women and the negative correlation between ET-1 in the
      umbilical vein and birth weight suggest that ET-1 plays a pathophysiological role
      in preeclampsia and other conditions with intrauterine growth restriction.

PMID- 8988524
TI  - Physiologic basis of ovulation induction.
AB  - Optimal regimens for ovulation induction depend on a sound, fundamental
      understanding of the physiology of ovulation. This chapter will review the
      endocrinology of folliculogenesis, with particular emphasis on the signaling
      pathways activated by FSH and LH. Important new information regarding the
      molecular mechanisms of signal transduction and the biologic responses that are
      produced will also be presented. Ultimately, a clearer understanding of
      mechanisms regulating the selection and promotion of the dominant follicle, as
      described here, will lead to advances in the field of ovulation induction and
      pregnancy in women.

PMID- 8988525
TI  - Ovulation induction in the nonestrogenized patient.
AB  - Women with nonestrogenized amenorrhea comprise a wide array of clinical problems.
      Identification and correction of the underlying pathologic process is the most
      appropriate approach to ovulation induction. Patients with central nervous system
      (CNS) or hypothalamic amenorrhea are treated with pulsatile gonadotropin
      releasing hormone (GnRH) when it is not possible to correct the underlying causes
      of these disorders. Gonadotropin therapy is needed for pituitary-related
      amenorrhea after conservative therapy is unsuccessful. However, ovarian
      hyperstimulation and multiple pregnancies are risks of gonadotropin therapy. The
      outcome is poor for ovarian failure or gonadotropin-resistant ovaries. An
      occasional pregnancy is established, but oocyte donation or adoption should be an
      early consideration. Women with nonestrogenized amenorrhea and a low or normal
      follicle-stimulating hormone (FSH) level can expect high ovulation and pregnancy
      rates with gonadotropin therapy when more conservative means are unsuccessful:
      Treatment is not likely to benefit those with elevated FSH levels.

PMID- 8988526
TI  - Ovulation induction in the estrogenized anovulatory patient.
AB  - Ovulation induction is one of the greatest success stories in reproductive
      endocrinology. With appropriate therapy in properly f1p4cted patients, the
      conception and live birth-rates in treated patients are almost indistinguishable
      from normal. In the estrogenized woman there are many different techniques to
      reverse the condition of chronic anovulation. With clomiphene citrate, up to 80%
      of patients will ovulate, and approximately half will conceive. In women who fail
      clomiphene therapy, injectable gonadotropins are usually successful in inducing
      ovulation. New protocols for administering these powerful agents have minimized
      the risk of ovarian hyperstimulation and multiple pregnancy. When medical therapy
      fails to result in successful ovulatory cycles, surgical treatments can be
      considered. Laparoscopic ovarian ablation has been shown to be effective
      treatment. Whether this less invasive surgery results in fewer adhesions than
      conventional ovarian wedge resection remains to be proven. By carefully
      considering each patient and individualizing treatment based on a full knowledge
      of alternatives, ovulation induction remains one of the most challenging and
      rewarding treatments in reproductive endocrinology.

PMID- 8988527
TI  - Evaluation and treatment of low responders.
AB  - Identification and treatment of low responders to ovulation induction is one of
      the most frustrating challenges in reproductive medicine. Because complex
      ovulation induction is required so frequently and is so expensive, efficient
      diagnosis of hyporesponders is critical. At present, the best techniques of
      evaluating ovarian reserve are basal follicle-stimulating hormone/Estradiol
      levels early in the proliferative phase and the clomiphene citrate challenge
      test. When poor responders are identified, strong consideration should be given
      to adjunctive approaches such as gonadotropin-releasing hormone analog and
      microdose flare or possibly, embryo hatching in those women undergoing in vitro
      fertilization.

PMID- 8988528
TI  - Ovulation induction in the ovulatory woman.
AB  - Controlled ovarian hyperstimulation is frequently employed as empiric therapy for
      the treatment of unexplained infertility, mild male factor, cervical factor, and
      treated endometriosis. Prescribed in the form of either clomiphene citrate or
      gonadotropins, it is often combined with intrauterine insemination and offered to
      patients as a less expensive and less invasive alternative to the assisted
      reproductive technologies. Efficacy studies for these regimens are very
      important, as patients who would appear to be ideal candidates for this empiric
      therapy frequently do not suffer from absolute infertility; rather they are often
      subfertile, and may conceive spontaneously given enough time. Although there are
      few well-designed, controlled trials that assess the effectiveness of this form
      of therapy, the majority of the published data do suggest an improvement in
      pregnancy rates when compared to expectant management.

PMID- 8988529
TI  - Reproductive toxicity of ovulation induction.
AB  - The development of ovulation-inducing drugs has enabled clinicians to more
      effectively treat the hypothalamic, pituitary, and ovarian abnormalities
      resulting in infertility. Pregnancy rates have been improved with the use of
      agents such as clomiphene citrate (CC), human menopausal gonadotropin [hMG or
      follicle-stimulating hormone (FSH) preparations], with gonadotropin-releasing
      hormone (GnRH) and its analogs, stimulating the development of multiple ovarian
      follicles and increasing the number of fertilizable oocytes. The use of these
      drugs is not without certain detrimental or "toxic" consequences. The negative
      effects from superovulation can occur during follicle development, decreasing the
      number of healthy oocytes and embryos capable of leading to viable pregnancy.
      Ovulation induction can lead not only to higher incidences of spontaneous
      abortions, and multiple and ectopic pregnancies, but also to poor pregnancy
      rates, due, in part, to asynchrony between embryonic development and the uterine
      environment. Diseases such as ovarian hyperstimulation syndrome (OHSS), resulting
      in the secretion of supraphysiologic levels of estradiol, can lend to severe
      health complications, possibly requiring hospitalization. Most drugs used for
      ovulation induction can lead to OHSS. Although incidences of OHSS following CC
      use are less frequent, CC has been associated with hot flushes, multiple
      gestations, visual disturbances, cervical mucus abnormalities, and luteal phase
      deficiency. Finally, there are reports that link any or all of the ovulation
      inducing drugs with a higher incidence of ovarian and breast cancer, however, a
      cause-effect relationship has yet to be proven.

PMID- 8988530
TI  - Prevention and treatment of ovarian hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of
      ovarian stimulation. Although the milder form is more common, particularly among
      patients undergoing gonadotropin stimulation for assisted reproductive
      technology, the severe form is rare. Classification schemes are clinically
      directed and useful in diagnosis and management of moderate and severe cases. The
      ovarian renin-angiotensin system, as well as vascular endothelial growth factor
      (VEGF)/vascular permeability factor (VPF) offers attractive theories as to the
      pathogenesis of this disorder. Unfortunately, clinical applications of these
      findings are not yet available. Possible prevention measures would include
      identification of patients at high risk, withholding human chorionic gonadotropin
      (hCG), using a gonadotropin-releasing hormone agonist to trigger ovulation, using
      a smaller dose of hCG, controlled gonadotropin drift, or avoidance of fresh
      embryo transfer by cryopreservation and frozen embryo transfer at a later date.
      Management of moderate to severe OHSS rests upon the principles of expanding
      intravascular volume and maintaining adequate urine output.

PMID- 8988531
TI  - Ovulation induction and ovarian malignancy.
AB  - Many couples faced with infertility are treated with ovulation inducing
      medicines. Recently, concerns have been raised about the possible risk of ovarian
      malignancy after such ovarian stimulation. Theories of pathogenesis for ovarian
      cancer include incessant ovulation, elevated pituitary gonadotropins, genetic
      predisposition, and chemical carcinogens. Protective factors include suppression
      of ovulation, pregnancy, and castration. Low numbers of exposed women who develop
      ovarian cancer make this a difficult research subject. Research to date
      demonstrates conflicting results, with some investigators reporting an increased
      risk of ovarian cancer with fertility drugs, whereas others do not. The likely
      magnitude of risk, if one believes a risk exists, may be two to three times that
      of the general population which is at most 4-5% in a woman's lifetime. The
      present uncertainty makes it challenging to apply this to today's practice of
      medicine. With continued efforts worldwide, we hope an understanding of this will
      be forthcoming.

PMID- 8988532
TI  - The evolution of new agents for ovulation induction.
AB  - The field of clinical ovulation-induction therapy has remained relatively static
      for over 30 years. This field promises to benefit from advances in our
      understanding of the biology of ovulation, and from exciting new work in the
      areas of molecular and cellular biology and in the biochemistry of steroids,
      gonadotropins, and their receptors. New therapies with recombinant gonadotropins
      and their analogues show promise for the near future. Advances in our ability to
      stimulate and suppress the reproductive axis through central mechanisms also show
      some promise. In the long term, our understanding of the mechanisms involved in
      folliculogenesis and oocyte maturation may be combined with an enhanced ability
      to dissect these processes that lead to disordered ovulation. Our improved
      understanding of the implantation process may well lead to an ability to create
      nearly universal nidation in women who are undergoing ART or who have
      implantation disorders. This article discusses some of the many new opportunities
      in the clinical and basic science of ovulation induction. New technologies, such
      as those available through the Human Genome Project, and the use of genetic
      manipulation of animal models will stimulate additional new avenues of research.

PMID- 8988533
TI  - Binding of peptides naturally presented by HLA-B27 to the differentially disease
      associated B*2704 and B*2706 subtypes, and to mutants mimicking their
      polymorphism.
AB  - B*2704 and B*2706 are closely related HLA-B27 subtypes of which the former but
      not the latter is associated to ankylosing spondylitis. Their peptide specificity
      relative to other disease-associated subtypes was analyzed by testing binding of
      self-peptides naturally presented by B*2705 or B*2702, and synthetic analogs, to
      B*2704, B*2706, and site-specific mutants mimicking their changes. Peptides with
      basic, aliphatic or aromatic C-terminal residues bound to B*2705 with similar
      affinity. In B*2704 C-terminal aliphatic/ aromatic residues were preferred.
      B*2706 discriminated drastically between polar and nonpolar C-terminal residues,
      showing strong preference for Leu and Phe, and less than B*2704 for basic and Tyr
      residues. Loss of single acidic charges (D > S77, D > Y116) increased preference
      for C-terminal Leu and Phe, but allowed efficient binding of peptides with basic
      residues or Tyr. Their gain (V > E152, H > D114) maintained wide C-terminal
      specificity, but severely impaired binding, presumably by disrupting interactions
      with internal peptide residues. This was compensated by Y116 in the double
      D114Y116 mutant. The specificity of B*2704 and B*2706 was explained only
      partially by the separate effects of single mutations, indicating that novel
      properties arise from concomitant changes at various positions. For instance,
      specificity of B*2706 for nonpolar C-terminal residues required simultaneous
      removal of Asp77 and Asp116. B*2706 differed from B*2705, B*2702, and B*2704 in
      its lower suitability for C-terminal Tyr, suggesting that this feature might be
      relevant for HLA-B27 association to spondyloarthropathy.

PMID- 8988534
TI  - The Fas antigen (CD95) on human lymphoid cells: epitope analysis with ten
      antibodies.
AB  - The expression of CD95 antigen was examined on adult and cord blood lymphocytes
      using a highly sensitive immunofluorescence/flow cytometric procedure. CD95 was
      expressed by the majority of circulating blood T cells in adults, and by a
      smaller proportion of CD4+ and CD8+ T cells in cord blood. The majority of
      circulating B cells did not react with seven CD95 antibodies, but three
      antibodies did stain B cells. In tonsil sections, CD95 was expressed throughout
      the tissue but germinal centres showed generally stronger staining than the
      surrounding follicular mantle and interfollicular areas. This was confirmed by
      flow cytometry, which showed expression preferentially on B cells with a germinal
      centre phenotype. Because different antibodies stained different proportions of B
      cells, CD95 epitopes were examined by inhibition, additive binding and protease
      susceptibility studies using a panel of ten CD95 antibodies. B cells apparently
      reacting selectively with CD95 antibodies were sorted and CD95 mRNA was reverse
      transcribed to cDNA and analyzed, in order to confirm the presence of CD95 in
      cells which reacted selectively and to explore the possible existence of CD95
      isoforms. The major cDNA band was identical in the two populations. Inhibition of
      N-glycosylation suggested that the epitopes detected differentially could not be
      accounted for by differential N-glycosylation.

PMID- 8988535
TI  - S-Endo 1, a pan-endothelial monoclonal antibody recognizing a novel human
      endothelial antigen.
AB  - A murine monoclonal antibody (mAb) S-Endo 1 has been produced to detect
      circulating endothelial cells detached from blood vessels in pathological
      conditions. We have demonstrated that the associated-antigen (S-Endo 1 Ag) was
      highly expressed on human vascular structure irrespective of tissue origin or
      vessel caliber. Its expression was not restricted to endothelium, since it was
      also detected at low level on smooth muscle cells, stroma cells and follicular
      dendritic cells. But its absence on hematopoietic cells made S-Endo 1 a helpful
      reagent to specifically discriminate endothelium from hematopoietic tissues.
      Biochemical characterization showed that S-Endo 1 recognizes a monomeric
      structure of approximately 118 kDa on cultured endothelial cells. S-Endo 1 was
      submitted to the 5th International Workshop (Boston, 1993) and did not cluster in
      any of the old or new endothelial clusters discussed at the conference,
      indicating its unique reactivity. Together with the data presented in this paper,
      this suggested that S-Endo 1 defines a previously undescribed endothelial
      molecule.

PMID- 8988536
TI  - Genetic heterogeneity between type 1a and type 1b insulin-dependent diabetes
      mellitus: HLA class II and TAP gene analysis.
AB  - The aim of this study was to compare the genetic susceptibility linked to the HLA
      Class II region genes of the Major Histocompatibility Complex in isolated insulin
      dependent diabetes mellitus (1a-IDDM) and insulin-dependent diabetes mellitus
      associated with another autoimmune endocrinopathy (1b-IDDM). HLA genes DRB1, DQA1
      and DQB1 were studied at the genomic level, as well as genes TAP1 and TAP2. One
      hundred and seventy-nine 1a-IDDM diabetic patients were compared with 83 1b-IDDM
      patients. While it appeared that common genetic traits characterize diabetes
      regardless of the subtype (1a or 1b), certain features differentiate the two
      forms of IDDM. Extending the analysis of risk haplotypes DRB1*03 and DRB1*04 to
      TAP genes elicited a difference between 1a-IDDM and 1b-IDDM patients. Haplo-type
      DRB1*03 was thus characterized in 1a-IDDM patients by a lower frequency of
      alleles TAP1-B (13.5%) and TAP2-B (16.2%), not found in 1b-IDDM patients (33.3%
      for each allele). Likewise, haplotype DRB1*04 is characterized in 1b-IDDM
      patients by a lower frequency of alleles TAP1-C (4.0%) and TAP2-B (8.0%) than in
      1a-IDDM patients (22.2% and 25.9%, respectively). In total, this study showed
      that extending the characterization of HLA Class II haplotypes to TAP genes
      discriminates between the forms of diabetes restricted to a specific pancreatic
      affection and those reflecting a wider autoimmune disorder affecting several
      organs.

PMID- 8988537
TI  - Molecular analysis of the DLA DR region.
AB  - The dog is an important model for studying organ transplantation. In order to
      develop a DNA-based typing system, a genomic analysis of the canine DR region of
      the MHC was undertaken. Southern analysis suggests the presence of two DRB genes
      in most dogs and all have one DRA gene. One dog out of 200 examined contains only
      one DRB gene. The DRA gene was mapped in one lambda phage clone. One DRB gene
      (DRBB1) was localized to two overlapping phage clones. Another DRB gene (DRBB2)
      was localized to two overlapping phage clones. Sequence analysis of the two DRB
      genes suggests that one gene is intact (DRBB1) and one gene is a pseudogene
      (DRBB2) because it lacks a splice acceptor signal for exon 3 and lacks exons 2
      and exon 4. Intron 1 and 2 sequence data from DRBB1 allow amplification of the
      polymorphic exon 2 which, in turn, can serve as a basis for developing a typing
      system for DRB.

PMID- 8988538
TI  - Molecular analysis of DLA-DRBB1 polymorphism.
AB  - The polymorphism of the canine major histocompatibility complex class II DRB
      gene, DRBB1, was analyzed. Exon 2 that encodes the polymorphic beta 1 domain was
      amplified by the polymerase chain reaction (PCR). The PCR product from 250 dogs
      was cloned and sequenced. Eighteen alleles were identified. Most of the variation
      in amino acid composition occurred at positions in the peptide binding site.
      Inheritance of these sequences showed Mendelian segregation with one or two
      alleles per dog. Cluster analysis of the nucleotide and predicted amino acid
      sequences subdivided the canine DRBB1 alleles into three major allelic groups.
      The number of nonsynonymous changes was higher than the number of synonymous
      changes in the putative antigen recognition sites indicative of positive
      selection. The data generated can serve as a basis for developing a typing assay
      for the canine DRBB1 gene.

PMID- 8988539
TI  - HLA gene and haplotype frequencies in Dutch blood donors.
AB  - We analyzed the HLA-A, -B, -C, -DR and -DQ phenotypes of 2,440 healthy,
      unrelated, Dutch Caucasoid blood donors and of 20,814 Dutch blood donors who were
      registered as volunteer bone marrow or platelet donors. Phenotype and gene
      frequencies, Hardy-Weinberg equilibrium fit and homozygosity were calculated as
      well as 2- and 3-locus haplotype frequencies, deltas, relative deltas and
      significance levels of the deltas. The population appears to be in Hardy-Weinberg
      equilibrium. Many haplotypes are in strong positive linkage disequilibrium. A
      phylogenetic tree, based on the HLA-A, -B and -DR gene frequencies of blood
      donors in different Dutch regions, reflects the limited but manifest
      heterogeneity of the Dutch population. Additionally we introduce a stepwise test
      for Hardy-Weinberg equilibrium and discuss the applicability of this test and of
      the single test for Hardy-Weinberg equilibrium for tissue typing quality control
      and for selection of split antigens prior to gene and haplotype frequency
      analyses.

PMID- 8988540
TI  - New HLA-DR haplotypes containing the DRB6 pseudogene.
AB  - An unexpected probe reaction pattern was observed in two samples during HLA-DR
      typing by PCR-Sequence Specific Oligonucleotide Probes. In order to confirm the
      unusual typings, samples were analyzed by PCR-Sequence Specific Primers, cloning,
      and nucleotide sequencing of the second exon of the HLA-DRB-genes. The confirmed
      DR, DQ phenotype for one sample was DRB1*0701, DRB4*01, DRB5*0101, DRB6*0201,
      DQB*0602, DQB1*0202. The phenotype of other sample was DRB1*1602, DRB1*1302,
      DRB3*0301, DRB6*0101, DQB1*0501, DQB1*0502. The first sample has the novel
      combination of DRB1*0701 with DRB5*0101 and DRB6*0201. The second sample has
      either DRB6*0101 together with DRB1*1602 in absence of any DRB5 allele or
      DRB6*0101 together with DRB1*1302, DRB3*0301. We postulate that the most likely
      haplotype in sample #1 is DRB1*0701; DRB5*0101, DRB1*0602 which could have arisen
      from gene conversion. The most likely haplotype in sample #2, DRB1*1602,
      DRB6*0101, DQB1*0502 would have arisen from an homologous recombination event.

PMID- 8988541
TI  - A new HLA-DQB1*0306 allele sharing motifs from DQB1*03032 and DQB1*04 sequences.
AB  - We have discovered a new HLA-DQB1 allele in a Japanese family, MAT. In the family
      the new allele segregates in three generations and demonstrates the positive
      association with DRB1*0901. We observed a novel RFLP pattern in the course of
      examining the modified PCR-RFLP method for HLA-DQB1 genotyping. The PCR-SSOP
      analysis also showed a new hybridized pattern. Sequence analysis of the allele
      indicates that it was generated by a gene conversion-like event between the
      HLADQB1*03032 and one of DQB1*04 contemporary alleles. This new allelic product
      did not react with all of allosera and monoclonal antibodies against DQ1, DQ2,
      DQ3, DQ4 and DQ7. The HLA molecule encoded by the allele is not defined by
      serology. This new allele was officially recognized and named DQB1*0306 by the
      WHO Nomenclature Committee in November 1995.

PMID- 8988542
TI  - Distribution of the HLA-A9 antigen family (A23, A24 and A2403).
AB  - Characterization of 50 local anti-HLA-A9 (A23 and/or A24) sera against the HLA
      A2403 antigen allowed the retrospective assignment of A2403 and the verification
      of A23 and A24 specificities in a panel of 9196 volunteer bone marrow donors. The
      six A2403 positive subjects identified were confirmed by PCR using four sequence
      specific primer mixtures. Population analysis showed the distribution and HLA-A/B
      linkage disequilibrium of HLA-A23 and A24 to be typical of a Northern European
      Caucasoid population. HLA-A2403 has a phenotype frequency of 0.00065 (gene
      frequency-0.00033) and is in linkage disequilibrium with HLA-B63 and possibly
      B35.

PMID- 8988543
TI  - Complete coding region of the new HLA-DQB1*0612 allele, obtained by RT-PCR.
AB  - A novel HLA-DQB1 allele was detected by oligotyping in the Bubi population of
      Equatorial Guinea. In order to characterize the new allelic variant, a RT-PCR
      method which permitted the cloning of its complete coding region was designed.
      With this method, we have determined the nucleotide sequence of the new DQB1*0612
      allele, related to *0604 and *0609 but differing from them at polymorphic codon
      70. A proposal for the improvement of the sequencing strategies of HLA class II
      alleles is made.

PMID- 8988544
TI  - DPA1*0105, a novel DPA1 variant in a negroid population.

PMID- 8988545
TI  - A novel recombinant HLA-B*39 allele (B*3910) in a South African Zulu.
AB  - The sequence of a new B*39 allele has been identified in a South African Zulu
      individual. This allele designated B*3910, differs at two nucleotide positions
      (246 and 272) from B*39011. The difference at position 246 is silent, while that
      at position 272 results in an amino acid change from cysteine (B*39011) to
      tyrosine (B*3910). As these same differences are found in other HLA-B alleles,
      they were probably introduced into the B*3910 sequence by a short gene conversion
      event with another allele. This finding provides further evidence for the
      diversification of HLA-B allelic sequences via recombination.

PMID- 8988546
TI  - Identification of a new HLA-B*55 allele, HLA-B*5503.

PMID- 8988547
TI  - Extensive conservation of upstream C4 promoter sequences: a comparison between
      C4A and C4B.
AB  - Basal levels of expression of complement C4 vary in individuals but it is unknown
      whether this is due to gene copy number, protein clearance rates or differences
      in expression. To investigate whether differences in the promoter region may
      influence transcription of the C4 genes, we sequenced the promoter region of the
      C4B1 gene from the HLA-A1, B8, C4AQ0, C4B1, DR3 haplotype and compared this with
      an equivalent C4A3 region. The promoter regions of the C4 genes were highly
      conserved, indicating that transcriptional differences are unlikely. An unusual
      feature of the alignment was the higher level of polymorphism in the RP genes
      past the breakpoint of deletion/duplication in a region where the highest
      conservation would be expected.

PMID- 8988548
TI  - A new allelic variant of HLA-DRB1*1101 (DRB1*11013) segregating in a Sardinian
      family.

PMID- 8988549
TI  - Nomenclature for factors of the HLA system, update July 1996.

PMID- 8988550
TI  - HLA-G transcription studies during the different stages of normal and malignant
      hematopoiesis.
AB  - Specific expression of the non classical class I HLA-G gene on trophoblasts, the
      only fetal tissue in contact with maternal cells which lack MHC class I antigens,
      may indicate a role of this gene in fetal-maternal tolerance. We recently
      reported HLA-G transcription in peripheral blood leukocytes. In this work, we
      have investigated HLA-G transcription in hematopoietic stem cells, in different
      hematopoietic lineages and in malignant cells by using a RT-PCR technique. PCR
      amplification with primers specific to the exon 2 and the 3' untranslated region
      has enabled to detect HLA-G transcription in B and T cell populations. No
      transcription was found in CD34+ cells, in thymocytes, in polynuclear cells, in
      monocytes and in natural killer cells. Among the malignancies analyzed, HLA-G is
      transcribed in 2 of 13 cases of acute leukemia characterized by a monocytic
      contingent, in 3 of 6 CLL and in all the cases of B-NHL (n = 6). No HLA-G
      transcription was detected in myeloma (n = 2). The splicing type does not seem to
      be linked to a lymphocyte subpopulation nor to a malignant proliferation stage.
      These results suggest that HLA-G is a marker of mature lymphoid cells and may
      play an immunological function as a peptide presenting molecule. HLA-G
      transcription in some cases of malignancy might indicate a contribution to the
      tumoral progression by blocking natural killing reaction.

PMID- 8988551
TI  - Observations on the prevalence of trypanosomosis in small ruminants, equines and
      cattle, in relation to tsetse challenge, in The Gambia.
AB  - The prevalence of trypanosome infections in Djallonke sheep and West African
      Dwarf goats at different sites in The Gambia showed a significant, positive
      correlation with contemporary assessments of tsetse challenge. A similar
      correlation was observed in village N'Dama cattle which showed comparable
      prevalence values in the same areas. Trypanosome prevalences also tended to be
      higher in horses and donkeys in areas with high tsetse challenge compared with
      sites with relatively few flies. A ranking of the numbers of tsetse blood-meals
      from cattle, small ruminants and equines (1:0.06: > 0.03) corresponded with the
      estimated biomass of these livestock groups (1:0.09:0.05). Observations on the
      grazing ranges of livestock showed that, while cattle foraged widely into tsetse
      infested habitat, sheep, goats and donkeys remained closer to the villages. This
      difference indicated that, under the management system practised in The Gambia,
      small ruminants and equines were probably exposed to a lower level of tsetse
      attack than cattle.

PMID- 8988552
TI  - Identification of a fibronectin-like molecule on the surface of Leishmania
      amastigotes.
AB  - The major surface glycoprotein of Leishmania gp63, a fibronectin-like molecule,
      plays a key role in parasite-macrophage interaction. In this article, we describe
      a cross-reactivity between an anti-fibronectin monoclonal antibody and the
      amastigote gp63 by means of immunoelectron microscopy and immunoblot.
      Immunoreactivity was found on the amastigote membrane and in the flagellar
      pocket. We suggest that gp63 may play a role in the protection and/or nutrition
      process of the parasite in the phagolysosomes of the macrophage.

PMID- 8988553
TI  - On the diagnostics of Sarcocystis in cattle: sarcocysts of a species unusual for
      Bos taurus in a dwarf zebu.
AB  - Sarcocysts from the musculature of a dwarf zebu born in a German zoo are
      described by light and transmission electron microscopy. In addition to the three
      named bovine Sarcocystis species (Sarcocystis cruzi, S. hominis, and S. hirsuta)
      a fourth species was found which was not previously reported from cattle. It
      mostly resembles Sarcocystis gracilis Ratz, 1909 from roe deer.

PMID- 8988554
TI  - A questionnaire survey of nematode parasite control practices on goat farms in
      Denmark.
AB  - A questionnaire survey to examine worm control practices on angora and other goat
      farms in Denmark was undertaken in 1993. Questionnaires were inserted in the
      July, 1993 issue of the official journal of the angora goat farmers in Denmark
      (Mohair News) and 72 questionnaires posted directly to other goat farms selected
      from a list of 150 farms registered with the Goat Breeders Association. Data from
      51 angora and 41 other goat farms indicated that anthelmintics were used on more
      than 80% of the farms. On 51% of the farms, no predetermined drenching programmes
      were followed. On 72% and 64% of the farms, kids (< 1 year of age) and adult
      goats (> 1 year old) were drenched 1-3, and two or three times per year,
      respectively. Only 9% of the farmers used the recommended weight of the heaviest
      animal in a herd to determine anthelmintic doses for groups of both kids and
      adult goats. Visual perception which may result in underdosing was used to
      determine weights for drenching on 41% and 69% of the farms for kids and adult
      goats, respectively. From 1986 to 1993, Class I anthelmintics (benzimidazoles)
      were the most commonly used. Anthelmintic classes were not alternated annually on
      the majority of farms, which would enhance selection for resistance. While the
      majority of farmers (58%) rotated goats regularly between paddocks, only 21%
      drenched the goats when being moved. Anthelmintic treatment for newly introduced
      goats was not carried out on 45% of 55 respondent farms, nine of which had
      imported stock. This increases the likelihood of introducing resistant worms to
      the farms.

PMID- 8988556
TI  - A survey of anthelmintic resistance in nematode parasites of goats in Denmark.
AB  - The occurrence of anthelmintic resistance in 15 goat herds in Denmark was
      investigated using the faecal egg count reduction test (FECRT), egg hatch assay
      (EHA) for thiabendazole (TBZ) and a microlarval development assay (LDA) for TBZ,
      levamisole (LEV) and ivermectin (IVM). Resistance to both benzimidazole (BZ) and
      levamisole (LEV) anthelmintics was detected on six farms, and to both BZs and IVM
      on one farm. Resistance to BZs was also detected on two farms and to LEV on two
      farms. Ivermectin resistance was present on one farm. Trichostrongylus and
      Ostertagia spp. were the predominant nematode species in both pre-treatment and
      post-treatment faecal cultures. In all nine instances where BZ resistance was
      detected in the FECRT, the LD50 values for TBZ in the EHA were higher than 0.5
      microM TBZ (0.1 microgram TBZ/ml), indicating resistance. LD50 values for TBZ in
      the LDA were also higher than 0.5 microM where resistance to BZs was detected in
      the FECRT, except two farms where LD50 values of 0.21 and 0.29 microM TBZ were
      recorded. LD50 values in the LDA for isolates declared resistant to LEV ranged
      from 0.78 to 5.62 microM LEV. For IVM, the two resistant isolates had LD50 values
      of 25 and 68 nM IVM. There were disagreements in the declaration of resistance
      between methods of calculating faecal egg count reduction percentage (FECR%)
      based on the arithmetic mean and those where geometric mean EPG is used.
      Similarly, inclusion of pre-treatment EPG or control group EPG in the calculation
      of FECR% influenced declaration of resistance.

PMID- 8988555
TI  - Worm control practices on sheep farms in Denmark and implications for the
      development of anthelmintic resistance.
AB  - A questionnaire survey was undertaken on sheep farms in Denmark to obtain
      information on sheep management and worm control practices. The questionnaires
      were inserted in the June and July, 1993 issue of the Danish Sheep Breeders
      Journal, circulated monthly to approximately 1200 sheep breeders nationwide. A
      total of 183 (11%) questionnaires were returned. A second questionnaire was
      posted to 50 of the 183 responding farmers to examine the repeatability of
      responses to the first questionnaire. The majority (97%) of the 183 farmers used
      anthelmintics. The mean number of doses per year for lambs (< 12 months old) and
      adult sheep (> 12 months old) were 1.9 and 2.3, respectively. Only 42% of the
      farms followed predetermined drenching programmes. Live weights were determined
      by visual appraisal on 45% and 84% of the farms for lambs and adult sheep,
      respectively. In calculating anthelmintic doses for groups of lambs and adult
      sheep, the recommended weights of the heaviest animals were only used on only 18%
      and 27% of the farms respectively. Benzimidazoles were the most commonly used
      anthelmintics from 1986 to 1993. Eighty one percent of 94 responding farmers had
      been using the same class of anthelmintic for 3 or more consecutive years.
      Information from this study indicated lack of knowledge about worm control
      strategies, anthelmintic use and the problem of anthelmintic resistance among the
      majority of Danish sheep farmers. The majority of responses to the questionnaire
      were repeatable at least to a fair degree except when farmers were asked to
      recall anthelmintics used in past years.

PMID- 8988557
TI  - Critical test evaluation (1977-1992) of drug efficacy against endoparasites
      featuring benzimidazole-resistant small strongyles (population S) in Shetland
      ponies.
AB  - Several compounds (n = 13 single or combinations; most at therapeutic dosages)
      were evaluated between 1977 and 1992 in critical tests (n = 91) against
      benzimidazole (BZ) resistant small strongyles (Population S) and several other
      species of internal parasites in Shetland ponies, mostly under 1 year old. The
      closed breeding herd, from which the test ponies were selected, had been treated
      every 8 weeks with cambendazole (CBZ) for 4 years (1974-1978) and oxibendazole
      (OBZ) for 14 years (1978-1992). Published field test data (1974-1992) on older
      ponies in the herd showed BZ resistance of small strongyles. Average efficacies
      in the present critical tests against small strongyles for OBZ (n = 59 animals)
      were high in early years (95% or higher), but gradually declined to a low of 1%
      in 1991. Side-resistance of small strongyles was evident in critical tests (n = 1
      6/single drug or combination) for several other BZs and a pro-BZ; ivermectin and
      piperazine were highly active, but pyrantel pamoate exhibited weak activity. BZ
      resistance was evident for six small strongyle species (Cyathostomum catinatum,
      Cyathostomum coronatum, Cylicocylus nassatus, Cylicostephanus calicatus,
      Cylicostephanus goldi, and Cylicostephanus longibursatus). Activity on bots,
      ascarids, large strongyles, and pinworms was essentially as expected, indicating
      no drug resistance.

PMID- 8988558
TI  - A study (1977-1992) of population dynamics of endoparasites featuring
      benzimidazole-resistant small strongyles (population S) in Shetland ponies.
AB  - Critical tests (91) were done between 1977 and 1992 in Shetland ponies to
      evaluate drug susceptibility and population dynamics (present paper) of
      endoparasites. The test ponies, most less than 1 year old, were from a herd where
      older animals were treated every 8 weeks initially with cambendazole (CBZ) (1974
      1978) and then with oxibendazole (OBZ) (1978-1992). Previous field test data
      (1974-1992) on older ponies in the breeding herd indicated the presence of
      benzimidazole (BZ) resistant small strongyles. Data on population dynamics from
      the present critical tests indicated that 28 species of small strongyles
      persisted over the study period in spite of initial susceptibility and later
      refractiveness of six species to both CBZ and OBZ. Changes in intensities and
      other aspects were observed for the six BZ-resistant species (Cyathostomum
      catinatium, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus
      calicatus, Cylicostephanus goldi, and Cylicostephanus longibursatus).
      Variabilities, some striking, were found in prevalence and intensity in bots,
      stomach worms, ascarids, eyeworms, large strongyles, pinworms and tapeworms.

PMID- 8988559
TI  - Activity of doramectin against nematode and arthropod parasites of swine.
AB  - The efficacy of doramectin, a novel avermectin, was assessed against both
      naturally-acquired and experimentally-induced infections of gastrointestinal
      roundworms, lungworms, kidneyworms, lice and mites in studies conducted across
      North America and Europe. Twenty-two studies evaluated efficacy against fourth
      larval and adult stages of the following nematode species: Hyostrongylus rubidus,
      Ascaris suum, Strongyloides ransomi, Oesophagostomum dentatum, Oesophagostomum
      quadrispinulatum, Trichuris suis, Metastrongylus spp. and Stephanurus dentatus.
      Efficacy was evaluated against the louse Haematopinus suis in six studies and
      against the mite Sarcoptes scabiei in four studies. A common study design was
      employed for each study type. In all studies, animals were allotted at random to
      a doramectin-treated or a saline-treated group. The doramectin-treated group
      received the drug at 300 micrograms kg-1 by intramuscular injection while the
      saline-treated group received saline by the same route. In the nematode studies,
      worm burdens were determined for each animal at slaughter 14-16 days after
      treatment. Efficacy against each nematode species/stage was assessed on the basis
      of percentage reduction in geometric mean worm burden in doramectin-treated
      animals compared with saline-treated controls. In louse and mite studies, counts
      were made immediately before treatment and then at weekly intervals for four
      weeks. Efficacy was based on a comparison of the level of infestation on the day
      of treatment with that on the last day of test. Data from individual studies were
      combined to derive a single estimate of efficacy against each of the parasite
      species represented in the study program. Efficacy of doramectin was 98% or
      greater against all nematode species except T. suis for which the efficacy was
      87% and 79% against adult and fourth larval stage, respectively. Efficacy was
      100% against both Haematopinus suis and Sarcoptes scabiei.

PMID- 8988560
TI  - Doramectin efficacy against the kidney worm, Stephanurus dentatus in sows.
AB  - Sixteen sows passing Stephanurus dentatus eggs in their urine were bought on the
      local market and placed in individual pens with solid concrete floors in an open
      sided bam. Water was supplied by nipple waterers and sows were fed individually
      1.8 kg feed daily. First, urine samples were taken at dawn on days -8 and -7 and
      weights were taken on day 0. Sows were assigned to one of two groups on the basis
      of average urine egg counts and weights. Group T1 sows were each injected IM in
      the neck with sterile saline at the rate of 1.5 ml per 50 kg and group T2 sows
      were each injected IM with doramectin at the rate of 300 micrograms kg-1 on day
      0. Urine samples were again taken on days 56 and 57 and the sows were necropsied
      on day 57. Urine of all doramectin treated sows were test negative for kidney
      work eggs on days 56 and 57 as was one control sow, whereas the average count for
      controls was 3762 eggs ml-1. No worms were found in doramectin treated sows and a
      total of 499 were found in the controls for an average of 62 per sow. The
      majority of worms were in the perirenal area and kidneys, a few were scattered in
      liver, lungs, abdominal muscles and peritoneal cavity. The efficacy of doramectin
      against Stephanurus dentatus in sows was 100% (P < 0.0001).

PMID- 8988561
TI  - Doramectin efficacy against gastrointestinal nematodes in pigs.
AB  - Four controlled trials with growing pigs were performed to determine efficacy of
      doramectin against natural and induced populations of nematodes. In Trial 1 (T1),
      20 pigs with natural infections were assigned to one of two like groups on the
      basis of weight, sex and worm egg counts. In Trial 2 (T2), 20 pigs with negative
      worm egg counts were assigned to one of two groups on the basis of weight and
      sex. Each pig was subsequently given (per os) 3000 Trichuris suis embryonated
      eggs; 2000 Ascaris suum embryonated eggs; 10000 Oesophagostomum spp. infective
      larvae and 10,000 Strongyloides ransomi infective larvae (SC injection). In Trial
      3 (T3), 20 pigs with negative worm egg counts were assigned as in T2, and each
      pig was subsequently given (per os) 2000 A. suum embryonated eggs, 15000
      Oesophagostomum quadrispinulatum infective larvae, and 2891 Hyostrongylus rubidus
      infective larvae. In Trial 4 (T4), 16 pigs with negative worm egg counts were
      each assigned to one of two groups as in T2 and were given (per os) 2670 T. suis
      embryonated eggs. On Day 0 of each trial, each pig of the control group was
      injected IM in the neck with sterile saline at the rate of 1.5 ml 50 kg-1. Each
      pig in the treated group of each trial was similarly injected with doramectin at
      the rate of 300 micrograms kg-1. All pigs were necropsied 14 or 15 days post
      treatment and parasites recovered by standard parasitological procedures.
      Efficacies against natural infections were: A. suum, 100%; Oesophagostomum spp.
      100%; H. rubidus, 99.4%; and Strongyloides ransomi, 99.9%. Efficacies against
      induced infections were: 4th stage A. suum, 100%; 4th stage O.dentatum, 99.9%;
      4th stage O.quadrispinulatum, 97.1 and 99.6%; 4th stage H. rubidus, 100%; adult
      S. ransomi, 100%; adult Trichuris suis in mixed infection, 54.1%; and in pure
      infection, 95.3%.

PMID- 8988562
TI  - Sero-surveillance of hypodermosis in a herd under therapeutic control. Effect of
      a low level of infestation.
AB  - A cattle herd from the experimental farm of INRA in Nouzilly has been treated for
      hypodermosis since October 1990. Additionally, a regional eradication scheme has
      been implemented in this area since autumn 1992. Bi-monthly warble counts were
      performed between March and July each year on an average of 200 animals. No
      warble was recorded in this herd from 1991 to 1994 with the exception of two
      dairy cows in 1993. In autumn 1994, therapeutic control measures were stopped.
      Serological surveys were performed in the autumn of each year from 1991 until
      1995. Anti-Hypoderma antibodies were found in 25%, 27.2%, 4.3%, 3.2% and 0% of
      the animals respectively. An experimental low infestation was conducted in the
      summer of 1994. During the spring 1994, third instars of Hypoderma bovis were
      collected from naturally infested animals. From a total of 13 pupae, six adults
      (four males and two females) emerged and were released in the herd of Nouzilly on
      24 June and 4 July. In October 1994 serological investigations revealed two
      animals seropositive for hypodermosis. This number increased to six in January
      1995. The antibody kinetics of these six animals remained parallel throughout the
      next 6 months: the titres increased up to April and started to fall in May to
      return to negative values in August. Manual examinations of the animals at weekly
      intervals between April and July revealed the presence of four warbled animals
      with one, one, two and three warbles respectively. The two other seropositive
      animals remained warble free. One other animal showed antibody titre fluctuations
      between negative and low positive values, but was warble free in the spring. In
      October 1995 all the animals of the herd were seronegative. The interpretation
      and the value of a sensitive immunodiagnosis in a large eradication programme are
      discussed and compared with warble counts, especially in the case of a low level
      of infestation.

PMID- 8988563
TI  - Natural superinfection of Parascaris equorum in a stall-confined orphan horse
      foal.
AB  - At 4 days of age, an orphan horse foal born on a pasture was placed in a parasite
      free stall. It was euthanized at 205 days of age and examination revealed
      numerous. Parascaris equorum specimens, ranging from 3.0 mm to adult size,
      indicating reinfections in the stall over an extended period of time. Initial
      infection of the foal was from stages on pasture. The foal had been observed
      repeatedly eating its own feces and the question is posed as to whether
      "recycling' of P. equorum eggs several times by coprophagy allowed time for
      embryonation and reinfection to occur.

PMID- 8988564
TI  - Thelazia rhodesii (Desmarest, 1828) infections in cattle in Mindanao,
      Philippines.
AB  - Thelazia rhodesii was found in the eyes of 149 of 643 bovine heads (23%) that
      were examined at the abattoir of Cagayan de Oro City, Philippines, during the
      period February 1994 to February 1995. In nearly half of the animals both eyes
      were infected and an average of 4.1 worms per infected animal was recovered. Of
      the 1286 eyes examined, 17% were infected; worm burdens ranged from one to 36
      (average 2.9) worms per infected eye. Monthly prevalence of infection ranged from
      13% to 36%. T. rhodesii infection was significantly more common in cattle of more
      than 3 years of age (25%) than in younger animals (15%). Ocular lesions were
      observed in 73 (11%) cattle; 22% of these were infected with T. rhodesii. There
      was no relationship between presence of T. rhodesii and ocular lesions.

PMID- 8988565
TI  - Genetic manipulations of microorganisms for the degradation of
      hexachlorocyclohexane.
AB  - Hexachlorocyclohexane (HCH) is an organochlorine insecticide which has been
      banned in technologically advanced countries. However, it is still in use in
      tropical countries for mosquito control and thus new areas continue to be
      contaminated. Anaerobic degradation of HCH isomers have been well documented but
      until recently there have been only a few reports on aerobic microbial
      degradation of HCH isomers. The isolation of these microbes made it possible to
      design experiments for the cloning of the catabolic genes responsible for
      degradation. We review the microbial degradation of HCH isomers coupled with the
      genetic manipulations of the catabolic genes. The first part discusses the
      persistence of residues in the environment and microbial degradation while the
      second part gives an account of the genetic manipulations of catabolic genes
      involved in the degradation.

PMID- 8988566
TI  - Flux analysis and control of the central metabolic pathways in Escherichia coli.
AB  - The growth of the bacterial cell involves the co-ordination of the fluxes of
      carbon into a considerable diversity of products that are the components of the
      cell. Fortunately the monomers from which the cell's polymers are made are
      themselves synthesised from a relatively small group of precursors that are the
      products of the central metabolic pathways. This simplification renders cell
      metabolism accessible to flux analysis, a method for handling experimental data
      to derive metabolic fluxes. Through such analysis of the growth of Escherichia
      coli ML308 on 11 single carbon sources in batch, turbidostat or chemostat culture
      general patterns are discernible. Most significant among these are that growth on
      different carbon sources is achieved without any obvious enzyme acting as a
      regulator of metabolic flux, except when acetate is the sole source of carbon. In
      this case a junction is created at which iso citrate dehydrogenase (ICDH) and
      isocitrate lyase (ICL) compete for their common substrate and this competition is
      resolved by partial inactivation of ICDH to match flux through ICL and this
      balance limits growth rate. In this sense, flux through ICDH and ICL is 'rate
      limiting'. Uptake of six of the remaining carbon inputs exceeds the capacity of
      the central metabolic pathways (CMPs) to sustain flux to the precursors required
      for growth and the CMPs are balanced by excretion of acetate. Restriction of
      carbon uptake by chemostat progressively diminishes growth rate and acetate
      excretion until acetate excretion is prevented. For the four remaining carbon
      sources, uptake is apparently restricted and the products are biomass, carbon
      dioxide and water. Carbon sources feeding the phosphorylated parts of the CMPs
      flux relatively more carbon to precursors (Pre-C) than CO2 when compared with
      carbon sources which feed into the non-phosphorylated pathways. Pre-C/CO2 ratios
      for the former are 1.73-3.91 and for the latter are 0.46-0.78. Flux analysis of
      all 11 carbon sources shows that there is an overabundant supply of 'energy' (ATP
      + [2H]), generated by the CMPs, in all phenotypes and conditions down to a
      glucose chemostat at mu of 0.72. This excess energy is a thermodynamic
      inefficiency which must be dissipated as heat. E. coli ML308 probably evolved in
      circumstances of 'feast' and 'famine'. The two strategies selected (excretion of
      surplus carbon and restriction of mu) would appear to be defences against
      'feast'. Presumably there are defences against 'famine'. These are not made
      obvious by flux analysis but allosteric control of irreversible enzymes would
      protect pools of essential nutrients from rapid depletion on the sudden onset of
      'famine'.

PMID- 8988567
TI  - The transcriptional apparatus required for mRNA encoding genes in the yeast
      Saccharomyces cerevisiae emerges from a jigsaw puzzle of transcription factors.
AB  - The number of identified yeast factors involved in transcription has dramatically
      increased in recent years and the understanding of the interplay between the
      different factors has become more and more puzzling. Transcription initiation at
      the core promoter of mRNA encoding genes consisting of upstream, TATA and
      initiator elements requires an approximately ribosome-sized complex of more than
      50 polypeptides. The recent identification and isolation of an RNA polymerase
      holoenzyme which seems to be preassembled before interacting with a promoter
      allowed a better understanding of the roles, assignments and interplays of the
      various constituents of the basal transcription machinery. Recruitment of this
      complex to the promoter is achieved by numerous interactions with a variety of
      DNA-bound proteins. These interactions can be direct or mediated by additional
      adaptor proteins. Other proteins negatively affect transcription by interrupting
      the recruitment process through protein-protein or protein-DNA interactions. Some
      basic features of cis-acting elements, the transcriptional apparatus and various
      trans-acting factors involved in the initiation of mRNA synthesis in yeast are
      summarized.

PMID- 8988568
TI  - Identification of Euro-Americans, Afro-Americans, and Amerindians from palatal
      dimensions.
AB  - Seven measurements were taken on 414 Euro-American, Afro-American, and Amerindian
      palates in an attempt to evaluate differences in dental arcade shape among these
      three groups. Width measurements across the palate at the first incisor, canine,
      second premolar, and second molar were taken directly on the dental arcade. The
      distances along the sagittal plane from the front of the palate to the level of
      these teeth were calculated from measurements taken between the right central
      incisor and the canine, second premolar and second molar. Discriminant functions
      computed from the measurements properly classified palates by group 66.0% of the
      time if sex is unknown. If sex is known to be male, other functions properly
      classified 65.7% of the sample; for sex known to be female 72.0% correct
      classification was achieved. Because these percentage are more than twice that
      expected from probability theory alone, it is concluded that the seven
      measurements are useful in determining ethnic group.

PMID- 8988569
TI  - Some considerations regarding the use of amino acid racemization in human dentine
      as an indicator of age at death.
AB  - An HPLC method is described for simultaneously obtaining the enantiomeric ratio
      of three amino acids (aspartic acid, serine, and glutamic acid) from dental
      collagen, with a view to using this information for estimating age at death.
      Results are reported from a sample of twenty three known age modern teeth, six
      known age 19th C. AD teeth, and two unknown age Romano-British teeth. It was
      found (as expected) that all three D/L ratios changed significantly with
      chronological age. Standard calibration techniques were used to estimate ages for
      the six 19th C. AD specimens from regression equations estimated from the modern
      specimens, and also to predict (for the first time) the error associated with
      such estimates. Errors using aspartic acid were found to be similar to those
      obtained by other methods of age estimation from dental evidence, serine, and
      glutamic acid providing much poorer age estimates. Additionally, a systematic
      difference in the age-enantiomeric ratio relationship was observed between modern
      and older dental samples. It is concluded that there is some fundamental
      difference in the observed enantiomeric ratios between modern teeth and older
      samples, possibly as a result of the chemical alteration of the dental proteins.

PMID- 8988570
TI  - Sleepwalking disorder and mens rea: a review and case report. Maricopa County
      Superior Court.
AB  - This paper examines complications of sleepwalking disorder (DSM-IV 307.46), an
      arousal disorder or parasomnia, in relationship to mens rea, or culpable mental
      state necessary to a finding of criminal responsibility. The legal history of
      criminal intent and insanity is reviewed. A case of indecent exposure is
      discussed in a man with a history of closed head injuries and sleepwalking
      disorder who was found standing naked in the middle of a busy urban thoroughfare
      in the wee hours of the morning and arrested. On psychiatric evaluation, the
      defendant was found to have a long-standing sleepwalking disorder. At trial,
      scientific literature and psychiatric expert testimony concerning sleepwalking
      disorder was presented. The psychiatrist opined that the defendant was probably
      sleepwalking at the time of the alleged offense. No rebuttal testimony was
      offered by the prosecution. The jury found the man not guilty. The author surveys
      the legal history of sleepwalking disorder and compares this example with others
      in which uncontrolled behavior during sleep has resulted in harm to the patient
      or to others. Clinical and forensic implications of the disorder are reviewed.
      The parasomnias' impact on forensic practice should be systematically studied.
      Intervention strategies should be refined and implemented.

PMID- 8988571
TI  - Fatal excited delirium following cocaine use: epidemiologic findings provide new
      evidence for mechanisms of cocaine toxicity.
AB  - We describe an outbreak of deaths from cocaine-induced excited delirium (EDDs) in
      Dade County, Florida between 1979 and 1990. From a registry of all cocaine
      related deaths in Dade County, Florida, from 1969-1990, 58 EDDs were compared
      with 125 victims of accidental cocaine overdose without excited delirium.
      Compared with controls, EDDs were more frequently black, male, and younger. They
      were less likely to have a low body mass index, and more likely to have died in
      police custody, to have received medical treatment immediately before death, to
      have survived for a longer period, to have developed hyperthermia, and to have
      died in summer months. EDDs had concentrations of cocaine and benzoylecgonine in
      autopsy blood that were similar to those for controls. The epidemiologic findings
      are most consistent with the hypothesis that chronic cocaine use disrupts
      dopaminergic function and, when coupled with recent cocaine use, may precipitate
      agitation, delirium, aberrant thermoregulation, rhabdomyolysis, and sudden death.

PMID- 8988572
TI  - The differential diagnosis of ritual abuse allegations.
AB  - OBJECTIVE: Because psychiatrists do not have a consistent way to classify and
      define the forms of child abuse that may be mistaken for ritual abuse, the
      objective of this paper is to create a comprehensive differential diagnosis of
      allegations of ritual abuse. METHOD: The authors reviewed 60 articles, chapters,
      and books that contained allegations of ritual abuse or behaviors that might be
      mistaken for ritual abuse, that were made by patients or caretakers. RESULTS:
      This paper clarifies the behaviors that represent or may be mistaken for ritual
      abuse: Cult-based ritual abuse, pseudoritualistic abuse, activities by organized
      satanic groups, repetitive psychopathological abuse, sexual abuse by pedophiles,
      child pornography portraying ritual abuse, distorted memory, false memory, false
      report due to a severe mental disorder, pseudologia phantastica, adolescent
      behavior simulating ritual abuse, epidemic hysteria, deliberate lying, and
      hoaxes. CONCLUSIONS: The differential diagnosis of allegations of ritual abuse is
      important in both clinical and forensic psychiatry. In some cases, it will not be
      possible to tell whether a particular allegation is factual or what the
      underlying mental processes are. It is important to separate the role of the
      mental health professional as therapist from the role as an expert witness in
      court.

PMID- 8988573
TI  - Summary of validation studies from twenty-six forensic laboratories in the United
      States and Canada on the use of the AmpliType PM PCR amplification and typing
      kit.
AB  - A cooperative study was undertaken to collect and summarize the results of
      validation studies from forensic laboratories in the United States and Canada on
      the use of the AmpliType PM PCR amplification and typing kit for genetic typing
      of forensic biological evidence. This report compiles data from 26 laboratories
      on: 1) reproducibility studies on DNA extracted from various samples, 2) genetic
      typing of DNA extracted from a variety of biological samples on various
      substrates, 3) the effects of exogenous chemicals, materials, and environmental
      factors on test results, 4) sensitivity studies to determine the least detectable
      amount of extracted genomic DNA that can be reliably typed, 5) analysis of
      mixtures containing two sources of genomic DNA, 6) cross-hybridization with DNA
      extracted from various nonhuman species, and 7) evaluation of assay performance
      on parallel studies with other genetic typing systems on proficiency test panels,
      mock cases, and adjudicated/nonprobative casework. Equivalent results were
      obtained by each laboratory that supplied data, demonstrating the reliability and
      consistency of the test. Overall, it can be concluded from this study that the
      AmpliType PM PCR amplification and typing kit meets the guidelines of the
      Technical Working Group on DNA Analysis Methods (TWGDAM) and there is general
      scientific acceptability of this kit for forensic DNA testing.

PMID- 8988574
TI  - Antisocial personality disorder, sexual sadism, malignant narcissism, and serial
      murder.
AB  - This paper examines the research on serial murder and its relationship to
      antisocial personality disorder and sexual sadism. The concept of malignant
      narcissism is also discussed. Case studies of serial killers are examined
      regarding the nature of sexual violation and crime scene behavior.

PMID- 8988575
TI  - Foraging by food deprived larvae of Neobellieria bullata (Diptera:
      Sarcophagidae).
AB  - Traditional entomological methods of estimating postmortem interval from
      developmental stages of fly larvae associated with the body are based on the
      premise that older larvae are not recruited from the surrounding environment. We
      found that food deprived second and third instar larvae of the fleshfly,
      Neobellieria bullata Parker, can locate beef liver over a distance of 33 cm,
      apparently by using chemical cues, and can crawl to the food within 90 min. The
      implications of these results are discussed with respect to methods of estimating
      postmortem interval by calculating rates of fly larvae development.

PMID- 8988576
TI  - Fatal air transport accidents involving athletic teams from the United States.
AB  - Team sports at multiple levels of competition have steadily grown more popular
      and more economically significant in the United States and Canada during the past
      150 years. Year-round competition across these large countries requires
      continual, reliable, and safe transportation of teams and their supporters, often
      by air, with the potential albeit small for loss of athletes, coaches, and entire
      teams in air crashes and other accidents. This paper reviews potential and actual
      accidents involving United States athletic teams from the 1930s to the present,
      including four fatal air charter crashes from 1960 through 1977. Common factors
      in crashes included inclement weather, component failure, human factors, and
      overloading or misloading aircraft. The safety of commercial and charter aviation
      has been significantly improved. However, weather, human factors, and ongoing
      maintenance and inspection of aircraft for safety remain significant problems
      which call for continued vigilance.

PMID- 8988577
TI  - A compilation of fatal and control concentrations of drugs in postmortem femoral
      blood.
AB  - A compilation of postmortem femoral blood concentrations of drugs is presented.
      The samples are collected from cases in which the cause of death was: A)
      certified intoxication by one substance alone, B) certified intoxication by more
      than one substance and/or alcohol, and C) certified other cause of death without
      incapacitation due to drugs. The concentrations were compared with blood
      concentrations detected in suspected drugged drivers (D), and with previously
      published fatal and therapeutic concentrations. The special features of this
      compilation are: 1) exclusively femoral blood concentrations are quoted, 2) all
      analyses are based on samples handled according to a standardized, quality
      controlled procedure, 3) two control groups are included, and 4) one-substance
      only intoxications are separated from other intoxications. The material is based
      on a selection of 15,800 samples sent to the Department of Forensic Chemistry in
      Linkoping, Sweden, during 1992 to 1995 from the six forensic pathology units in
      Sweden, and the list includes 83 drugs. The compilation includes drugs, where
      previously published data are scarce. Furthermore, the data gathered from cases
      with other cause of death than intoxication (group C) constitute a new kind of
      reference information, which probably offers a better estimate of obviously non
      fatal levels in postmortem blood than any compilation of therapeutic
      concentrations in living subjects. The possible factors influencing postmortem
      drug concentrations are discussed.

PMID- 8988578
TI  - Possible markers for postmortem drug redistribution.
AB  - The possibility that postmortem biochemical changes in blood might parallel drug
      redistribution and thus serve as markers was explored in a detailed case study.
      Eighteen blood and 14 tissue and fluid samples were taken at autopsy 16 h after
      the death of a 34-year-old female from amitriptyline overdose. Ranges of drug
      concentrations in blood were amitriptyline 1.8 to 20.2 micrograms/mL,
      nortriptyline 0.6 to 7.3 micrograms/mL, levels were lowest in femoral vein and
      highest in pulmonary vein blood. Corresponding levels of 17 amino acids showed
      markedly different patterns of site-to-site variability. There was a strong
      positive correlation between individual amino acid and drug concentrations in
      pulmonary blood samples (n = 5), particularly for glycine, leucine, methionine,
      serine, and valine. In blood samples from the great veins and right heart (n =
      10), the correlation was less strong (r = 0.6 to 0.7). Methionine showed a strong
      positive correlation in pulmonary samples (r = 0.93), and negative correlation in
      great veing samples (r = -0.68). Lactic acid showed a strong negative correlation
      in pulmonary samples (r = -0.93) but a positive correlation in great vein samples
      (r = 0.71). Alanine aminotransferase, alkaline phosphatase, aspartate
      aminotransferase, gamma-glutamyl transferase, glucose, and bilirubin had a weak
      positive correlation with drug levels in great vein samples but not pulmonary
      samples. The results suggest that hepatic enzymes are relatively poor markers for
      postmortem hepatic drug shifts but that amino acids, particularly methionine, may
      be useful markers for pulmonary drug shifts.

PMID- 8988579
TI  - Three-dimensional imaging in forensic anthropology: a test study using the
      Macintosh.
AB  - Forensic anthropologists have unique, albeit usually fleeting, access to modern
      skeletal remains. By constructing a database of three-dimensional images, such
      remains can be accessed long after the remains are gone. A method is proposed
      which uses Macintosh hardware and NIH Image software to preserve remains
      digitally through red-blue three-dimensional imaging techniques. Additionally,
      the qualitative and quantitative accuracy of these images is assessed. By
      creating this type of forensic database, anthropologists can address issues such
      as populational variance, thereby using modern forensic skeletal remains to
      explore some of the fundamental issues within anthropology.

PMID- 8988580
TI  - Recommended technique for brain removal to retain anatomic integrity of the
      pineal gland in order to determine its size in sudden infant death syndrome.
AB  - A standardized removal and dissection procedure is presented for human infant
      brain. A previously unreported cistern of the pineal gland must be severed at
      autopsy in order to preserve the gland's anatomic integrity during brain removal.
      Utilization of these methods to investigate Sudden Infant Death Syndrome brain
      tissue should facilitate interdisciplinary studies and comparisons of inter
      agency findings. We use these dissection procedures to extend our findings on
      reduced pineal gland size as an anatomic marker assisting the forensic
      pathologist in making the diagnosis of Sudden Infant Death Syndrome.

PMID- 8988581
TI  - Skin scraping, cupping, and moxibustion that may mimic physical abuse.
AB  - Physical abuse and child abuse can manifest themselves as many different
      appearances. However, there are some cultural practices of Oriental medicine that
      may mimic physical and/or child abuse. This paper will discuss the practice of
      skin scraping, cupping, and moxibustion, which has been misdiagnosed as
      physical/child abuse by unfamiliar examiners.

PMID- 8988582
TI  - HPLC/MS determination of buprenorphine and norbuprenorphine in biological fluids
      and hair samples.
AB  - An original method, based upon HPLC (high performance liquid
      chromatography)/Ionspray-MS, has been developed for the identification of
      buprenorphine (BUP) and norbuprenorphine (norBUP) in biological fluids and hair
      samples. Biological fluids (2 mL) are extracted at pH 8.4 by CHCl3/2-propanol/n
      heptane (25:10:65, v/v) after addition of deuterated BUP (BUP-d4, 10 ng). Hair
      samples (40 mg) are extracted in the same conditions after decontamination by
      CH2Cl2, mechanical pulverization, addition of BUP-d4 (1 ng), acidic incubation (1
      mL 0.1 N HCl, 56 degrees C overnight), then neutralization by NaOH. Analytes are
      separated on a 4-microns NovaPak C18 (Waters) column (150 by 2.0 mm, ID) with a
      mobile phase of acetonitrile/2 mM NH4COOH buffer, pH 3.0 (80:20, v/v; flow rate
      200 microL/min; post column split 1:3). Detection is done by a Perkin-Elmer Sciex
      API-100 mass analyzer equipped with an ISP interface (nebulizing and curtain
      gas:99.95-% N2; main settings: orifice + 50 V, electron multiplier + 2400 V). The
      mean retention times for BUP, BUP-d4, and norBUP are 5.84, 5.79, and 4.42 min,
      respectively. For all compounds, mass spectra exhibit a unique, protonated
      molecular ion [M + H]+ at m/z 414 (norBUP), 468 (BUP), and 472 (BUP-d4), without
      any significant fragmentation. The lower limits of detection are 0.10 and 0.05
      ng/mL blood, and 4 and 2 pg/mg hair for BUP and norBUP, respectively. BUP and
      norBUP concentrations measured in hair from six addicts under substitutive
      therapy by BUP ranged from 4 to 140 pg/mg, and from nondetected to 67 pg/mg,
      respectively. The good performances of this method in terms of both sensitivity
      and specificity make it a convenient alternative to HPLC/coulometry and GC/MS for
      the separate analysis of BUP and norBUP in biological samples.

PMID- 8988583
TI  - An improved high resolution single method for orosomucoid ORM1 and ORM2
      phenotyping.
AB  - An improved high resolution single method for orosomucoid ORM1 and ORM2
      phenotyping using isoelectric focusing (IEF) in wide-scales ultrathin layer
      polyacrylamide gels of pH range 4.2 to 4.9 is presented. The method is reliable,
      simple, and provides an alternative for the three currently required ones for
      typing this genetic system.

PMID- 8988584
TI  - Highly informative single-stranded conformation polymorphism (SSCP) of short
      tandem repeats in DNA identification.
AB  - The analysis of short tandem repeats (STR) by PCR is a useful technique widely
      used in DNA identification. Some loci have alleles differing in the number of
      complete repeat units, whereas others are polymorphic with alleles differing even
      to the level of a single base. Minor differences in the sequence of STR can
      confuse the analysis when the PCR product are poorly resolved in denaturing PAGE.
      The study by SSCP of STR in loci CSF1PO, TPOX, and THO1 and the alleles of locus
      DIS80 is shown in a representative case of paternity dispute. The analysis of
      short tandem repeats (STR) by the conformation polymorphisms of single-stranded
      DNA (SSCP) clearly enhanced the degree of resolution. The high resolution of SSCP
      of the STR may be the result of the arrangement of very prominent secondary
      structure and conformation due to the primary repetitive sequence. The method may
      be of particular interest to distinguish STR with similar PAGE mobility under
      denaturing conditions and to distinguish tandem repeats of the same size but
      different sequence.

PMID- 8988585
TI  - Population study of the HUMTH01, HUMVWA31A, HUMF13A1, and HUMFES/FPS STR
      polymorphisms in the north of Portugal.
AB  - Allele and genotype frequencies of four short tandem-repeat loci were determined
      in a population sample from the North of Portugal using the polymerase chain
      reaction (PCR). After denaturing PAGE, 6 alleles were identified for HUMTH01 (n =
      419), 9 alleles for HUMVWA31A (n = 376), 12 alleles for HUMF13A1 (n = 232), and 5
      alleles for HUMFES/FPS (n = 409). No deviation from Hardy-Weinberg equilibrium
      was found. The allele frequencies observed are similar to those of the European
      populations compared. The combined power of discrimination is 0.999.

PMID- 8988586
TI  - Genetic variations at four tetrameric tandem repeat loci in Korean population.
AB  - Allele and genotype frequencies for four tetrameric short tandem repeat (STR)
      loci, HumFES/FPS, HumFOLP23, HumGABRB15, and HumCYAR04, have been determined by
      polymerase chain reaction (PCR) amplification and subsequent polyacrylamide gel
      electrophoresis from approximately 200 genetically unrelated Koreans. This method
      allows a single base pair resolution and rapid typing with silver staining. The
      allele and genotype distributions satisfy Hardy-Weinberg expectation. Also, these
      STR loci have proven to be useful for forensic analyses and paternity tests in
      which the variable number of tandem repeat (VNTR) loci have some limitations.

PMID- 8988587
TI  - Co-amplification of the amelogenin and HLA DQ alpha genes: optimization and
      validation.
AB  - An optimized PCR-based system allowing the co-amplification of the HLA DQ alpha
      and the amelogenin genes has been developed and validated, enabling simultaneous
      identity testing and sex determination. Sensitivities below 100 pg of human DNA
      were obtained, using a convenient, high resolution agarose gel system and
      ethidium bromide staining. Comparison of several co-amplification methods
      revealed that the best sensitivities and most consistent results were obtained
      using a hotstart technique employing an inactivating antibody to Taq polymerase.
      HLA DQ alpha typing results were reliably obtained using the co-amplification
      process. The sensitivity and ease of this system rendered it directly applicable
      to forensic analyses. The optimized techniques described here have been validated
      and successfully applied to forensic cases including People vs. Trujillo, in
      which the California Superior Court accepted these techniques as scientifically
      reliable and admissible. Work currently in progress has demonstrated that the
      described protocol may also be used to co-amplify the amelogenin gene with the
      AmpliType PM (polymarker) system, allowing identity testing at six loci in
      addition to sex determination.

PMID- 8988588
TI  - Estimation of age from teeth by amino acid racemization: influence of fixative.
AB  - To determine the age of a subject from teeth accurately utilizing the
      racemization rates of amino acids, standard samples of the same tooth species
      from the same jaw are necessary as controls, as well as data for identification.
      However, standard teeth are generally stored in fixatives such as ethanol and
      formalin. We investigated and compared the degree of progression of racemization
      of dentinal aspartic acid in teeth stored in 95% ethanol, 10% formalin, or 10%
      neutral formalin fixatives. The racemization rate of dentinal aspartic acid in
      teeth stored in 10% neutral formalin was the highest, followed by that for teeth
      stored in 10% formalin then that for teeth stored in 95% ethanol. Teeth stored in
      these fixatives at 15 degrees C showed almost no progression of racemization. The
      racemization ratio (D/L ratio) in teeth extracted 10 years previously was almost
      unchanged from that at the time of extraction, and allowed an accurate evaluation
      of the subjects age at tooth extraction.

PMID- 8988589
TI  - Contribution of microscopic plant anatomy to postmortem bone dating.
AB  - The authors describe a microscopical method of studying plant anatomy for
      estimating the age of vegetal organs which can help to date bones. This procedure
      was not based on counting the number of annual rings, as usually, but on
      demonstrating a completely primary structure without development of secondary
      formations; this material was considered as a part of a young root system whose
      development would correspond to about one year. The usefulness and limits of this
      procedure are discussed.

PMID- 8988590
TI  - Gas residues of engine starting fluid in postmortem sample from an arsonist.
AB  - Diethyl ether was found in samples of the blood, urine, and lung from a fire
      victim. Because the lung also carried a number of low-boiling paraffins, it was
      inferred that the detected compounds came from engine starting fluid, which the
      victim apparently had been exposed to while be intentionally used it as an
      accelerant to start the fire. The reported death illustrates the value of
      searching post mortem samples for highly volatile residues of possible arson
      accelerants.

PMID- 8988591
TI  - Sudden unexpected death in young adult due to right ventricular dysplasia.
AB  - This case report illustrates a rare familial cardiomyopathy first reported in the
      medical literature in 1982 known as right ventricular dysplasia (right
      ventricular cardiomyopathy). The patient is a young woman with a history of
      cardiac arrhythmias suspected to be associated with prolapsed mitral valve who
      presented to the Berks Country Coroner's office as a sudden unexpected death in a
      young adult. It is important to recognize the illustrated classic cardiac
      pathology of this rare entity for clinical management, as an anatomic explanation
      of cause of sudden death and for the accumulation of statistics to establish
      frequency, conditions of predisposition, response to therapy and predicted
      outcome.

PMID- 8988592
TI  - An electrocution death of an infant who had received an electric shock from an
      uncovered oval shaped lamp switch in his mouth while in a hospital.
AB  - A male infant aged one year and nine months was found dead on a bed after
      admission to hospital with suspected pneumonia. The patient apparently put an
      uncovered oval shaped lamp switch (pendant switch) into his mouth and died of
      electric shock after contacting the exposed wires of the switch (100 V, 60 Hz
      alternating current). There were extensive first- to fourth-degree burns on the
      inner surface of the both lips. Because the histological findings were consistent
      with electric burns and the burns showed vital reactions, electric shock was
      judged to be the cause of death. The pendant switch is normally a very convenient
      piece of bedside equipment for inpatients. However, when the patient is an infant
      who naturally puts all the objects into the mouth, such a switch should be placed
      out of reach, and it should be certain that the cap is not loose.

PMID- 8988593
TI  - Detection of alprazolam in three cases of methadone/benzodiazepine overdose.
AB  - Benzodiazepine abuse is common among clients at methadone maintenance clinics.
      Diazepam and lorazepam are readily detected by immunological screening methods
      and confirmed by GC/MS. Alprazolam has been relatively difficult to confirm. We
      recently reported a modification of an existing serum HPLC procedure which allows
      us to analyze whole blood. We report here three cases of fatal drug overdose
      caused by co-ingestion of methadone and alprazolam. In all three cases,
      alprazolam was detected by HPLC and could not be identified by alkaline
      extraction GC/MS. Postmortem blood concentrations of methadone were at the lower
      range or below the concentrations previously identified in methadone overdose
      fatalities, suggesting an increased risk from co-ingestion of methadone and
      alprazolam.

PMID- 8988594
TI  - Fatal ephedrine intoxication.
AB  - A 28-year-old white female with a history of two prior suicide attempts was found
      dead in her home by her common law husband. Autopsy findings were unremarkable
      except for partially dissolved ephedrine tablets in the stomach contents.
      Quantitation of ephedrine was by gas chromatography/mass spectrometry (GC/MS)
      following liquid/liquid extraction from alkaline samples and pentafluoropropionic
      acid derivatization. Significant toxicological finding included ephedrine; blood,
      11 mg/L; liver, 24 mg/kg; kidney, 14 mg/kg; brain, 8.9 mg/kg; and amitriptyline;
      blood, 0.33 mg/kg; liver 7.8 mg/kg. The ephedrine values found far exceed those
      associated with therapeutic administration and are consistent with the few
      reported cases of severe ephedrine intoxication. The cause of death was
      determined to be fatal ephedrine intoxication and manner of death suicide.

PMID- 8988595
TI  - Bastadin 20 and bastadin O-sulfate esters from Ianthella basta: novel modulators
      of the Ry1R FKBP12 receptor complex.
AB  - New compounds bastadin 20 (9), 15,34-O-disulfatobastadin 7 (10), and 10-O
      sulfatobastadin 3 (11) were isolated from Ianthella basta collected in Exmouth
      Gulf, Western Australia. Compounds 10 and 11 exhibited moderate differential
      activity as SR Ca2+ channel agonists (EC50 13.6 and 100 microM, respectively) of
      the Ry1R FKBP12 complex, while the potency of 9 was almost half that of 10 (EC50
      20.6 microM). The problem of dereplication of bastadins was addressed using 1H
      NMR "fingerprinting" of MeO signals in the corresponding permethyl bastadin
      derivatives.

PMID- 8988596
TI  - Syringin 4-O-beta-glucoside, a new phenylpropanoid glycoside, and costunolide, a
      nitric oxide synthase inhibitor, from the stem bark of Magnolia sieboldii.
AB  - Syringin 4-O-beta-glucoside (1), a new phenylpropanoid glycoside, and costunolide
      (2) were isolated from the stem bark of Magnolia sieboldii. The structures were
      determined by spectroscopic and chemical methods. Costunolide (2) exhibited
      strong nitric oxide synthase inhibitory activity in the endotoxin-activated
      murine macrophage, J774.1.

PMID- 8988598
TI  - Biological activities of the nortropane alkaloid, calystegine B2, and analogs:
      structure-function relationships.
AB  - Calystegines, polyhydroxy nortropane alkaloids, are a recently discovered group
      of plant secondary metabolites believed to influence rhizosphere ecology as
      nutritional sources for soil microorganisms and as glycosidase inhibitors.
      Evidence is presented that calystegines mediate nutritional relationships under
      natural conditions and that their biological activities are closely correlated
      with their chemical structures and stereochemistry. Assays using synthetic (+)-
      and (-)-enantiomers of calystegine B2 established that catabolism by Rhizobium
      meliloti, glycosidase inhibition, and allelopathic activities were uniquely
      associated with the natural, (+)-enantiomer. Furthermore, the N-methyl derivative
      of calystegine B2 was not catabolized by R. meliloti, and it inhibited alpha
      galactosidase, but not beta-glucosidase, whereas the parent alkaloid inhibits
      both enzymes. This N-methyl analog therefore could serve to construct a cellular
      or animal model for Fabry's disease, which is caused by a lack of alpha
      galactosidase activity.

PMID- 8988597
TI  - Antimycobacterial cycloartanes from Borrichia frutescens.
AB  - In a bioassay-guided search for antimycobacterial compounds from higher plants of
      the southeastern United States, we have chemically investigated the sea daisy
      (Borrichia frutescens) from coastal marshes of Louisiana for their active
      constituents. Bioactive chromatographic fractions provided two new triterpenes,
      (24R)-24,25-epoxycycloartan-3-one (1) and (23R)-3-oxolanosta-8,24-dien-23-ol (4),
      and (3 alpha H, 24R)-24,25-epoxycycloartan-3-ol (3a). Compound 3a had been
      previously isolated as a mixture of C-24 epimers. The structures of 1, 3a, and 4
      were established by spectroscopic methods and chemical transformations, and the
      molecular structures of 1 and 4 were determined by single-crystal X-ray
      diffraction. In a radiorespirometric bioassay against Mycobacterium tuberculosis,
      the epoxycycloartanes 1 and 3a exhibited minimum inhibitory concentrations of 8
      micrograms/mL. In contrast, the lanostadiene-type triterpene 4 showed no
      significant inhibition at 128 micrograms/mL, as did the acetate 3b. Cytotoxicity
      for Vero cells gave IC50 values of 71.8, 39.8, and 103.6 micrograms/mL for
      triterpenes 1, 3a, and 4, respectively.

PMID- 8988599
TI  - New triterpenoid saponins from Gynostemma pentaphyllum.
AB  - Three new triterpenoidal saponins (1-3), together with the known compound 4, were
      isolated from a MeOH extract of the aerial parts of Gynostemma pentaphyllum.
      Their structures were elucidated on the basis of chemical and spectral methods,
      such as 1H-1H DQFCOSY, HMQC, HMBC, and TOCSY NMR spectra. The aglycon moiety of 1
      and 2 is a new dammarane-type triterpene 12-oxo-2 alpha, 3 beta, 20 (S)
      trihydroxydammar- 24-ene.

PMID- 8988600
TI  - Antiplatelet arylnaphthalide lignans from Justicia procumbens.
AB  - Fractionation of the EtOH extract of Justicia procumbens, guided by antiplatelet
      bioassay, led to the isolation of nine known arylnaphthalide lignans, neojusticin
      A (1), justicidin B (2), justicidin A (3), taiwanin E methyl ether (4),
      neojusticin B (5), chinensinaphthol methyl ether (6), taiwanin E (8),
      chinensinaphthol (9), and diphyllin (10), and a new arylnaphthalide lignan that
      was characterized by spectral means as 4'-demethylchinensinaphthol methyl ether
      (7). Compounds 1, 2, 4, and 8 significantly inhibited platelet aggregation.

PMID- 8988601
TI  - Fusaricide, a new cytotoxic N-hydroxypyridone from Fusarium sp.
AB  - A new cytotoxic N-hydroxypyridone, fusaricide (1), was isolated from a Fusarium
      sp. Its structure was solved by X-ray diffraction and spectroscopic analyses.

PMID- 8988602
TI  - A new derivative of glucose and 2-C-methyl-D-erythritol from Ferula sinaica.
AB  - A new glucose derivative (1) and 2-C-methyl-D-erythritol (2) were isolated from
      the leaves of Ferula sinaica. The two structures were elucidated by highfield NMR
      spectroscopy, and that of 1 was confirmed by X-ray diffraction analysis.

PMID- 8988603
TI  - A 1,4-disubstituted quinolizidine from a Madagascan mantelline frog (Mantella).
AB  - A major alkaloid, 217A, in skin extracts of a mantelline frog (Mantella baroni)
      was isolated by HPLC and the structure defined by 1H-NMR spectral analysis as
      (1R,4S,10S)- or (1R,4R,10R)- 1-methyl-4-(Z)-(1-pent-2-en-4-ynyl) quinolizidine
      (1). Four other alkaloids-207I (2), 231A (3), 233A (4), and 235E' (5)-detected in
      frog skin extracts are proposed to be 1,4-disubstituted quinolizidines based on
      diagnostic mass and FTIR spectra.

PMID- 8988604
TI  - Cell-based screen for identification of inhibitors of tubulin polymerization.
AB  - This assay is based on morphological changes of rat glioma cells treated with db
      cAMP. The db-cAMP treatment induces a tubulin-dependent change causing the cells
      to acquire a spherical shape. Pretreatment with tubulin inhibitors brings about
      the disintegration of tubulin polymer and/or prevents its polymerization. Cells
      with inhibited tubulin fail to respond to db-cAMP treatment. Cells treated with
      inhibitors of tubulin polymerization are then separated from the spherical cells
      by aspiration. A semiautomated scanning procedure evaluates the final culture
      density and yields graphical data.

PMID- 8988605
TI  - Antiinflammatory activity of coumarins from Santolina oblongifolia.
AB  - Four coumarins were isolated from the EtOAc extract of the flower-tops of
      Santolina oblongifolia Boiss. (Compositae). They were identified as 7
      methoxycoumarin (herniarin) (1), 6,7-dihydroxycoumarin (aesculetin) (2), 6
      methoxy-7-glucosidylcoumarin (scopolin) (3), and 6-hydroxy-7-methoxycoumarin
      (scopoletin) (4). This is the first report of the isolation of aesculetin and
      scopolin from the genus Santolina. The isolated coumarins showed marked activity
      as inhibitors of eicosanoid-release from ionophore-stimulated mouse peritoneal
      macrophages.

PMID- 8988606
TI  - Structure and stereochemistry of pseudolarolide J, a novel nortriterpene lactone
      from Pseudolarix kaempferi.
AB  - Pseudolarolide J (1), a novel nortriterpene lactone, has been isolated from the
      seeds of Pseudolarix kaempferi and structurally characterized from spectral data
      and X-ray crstallographic analysis.

PMID- 8988607
TI  - Naturally occurring proline analogues.

PMID- 8988608
TI  - Energy transfer reactions involving carotenoids: quenching of chlorophyll
      fluorescence.
AB  - Carotenoids have a key role in photosynthesis in photosynthetic systems,
      transferring excitation energy to chlorophyll (Chl) during light harvesting.
      These pigments also protect the photosynthetic apparatus from photodamage by
      quenching the Chl triplet state and singlet oxygen. In addition, in higher plants
      and some algae, a number of xanthophylls also have the ability to deactivate
      excited Chl under conditions of excess excitation via the operation of the
      xanthophyll cycle (violaxanthin<-->antheraxanthin<-->zeaxanthin or
      diadinoxanthin<-->diatoxanthin). The formation of zexanthin (or diatoxanthin) can
      be clearly correlated with the non-photochemical quenching of Chl fluorescence,
      and is now recognized as a major photoprotective process in higher plants and a
      number of algal genera. The interconversion of these xanthophylls in response to
      a changing light environment alters the extent of their carbon-carbon double bond
      conjugation, which, in turn, affects the excited state energies and lifetimes of
      the carotenoids and may also alter their structure/conformation and
      hydrophobicity. The possible roles of these photophysical and physicochemical
      changes in the mechanism(s) of xanthophyll-mediated energy dissipation via
      quenching of Chl fluorescence are discussed.

PMID- 8988610
TI  - Targeted gene transfer in eucaryotic cells by dye-assisted laser optoporation.
AB  - The blue beam of an Argon laser (488 nm) has been focused on the cell membrane in
      the presence of phenol-red, an usual component of cell culture media, through a
      100 x objective. At the site of the beam impact, due probably to local
      temperature changes, the cell membrane modifies its permeability. As a
      consequence of the hit, circular areas, whose radius may be apparently regulated
      by changing the irradiation time and/or the radiation intensity (energy), appear
      on the wall, last for a short time and fade spontaneously within 1-2 minutes. No
      evident sings of cell injury or hurt have been observed afterward. Plasmid DNA,
      purposely added to culture fluid, easily slips in the cytoplasm; utilizing such
      approach, thereafter indicated as "optoporation', we have successfully
      transfected two genes, namely beta-galactosidase and chloramphenicol-acetyl
      transferase in murine NIH3T3 fibroblasts. Therefore optoporation represents an
      additional procedure for gene transfer with several advantages over already
      available methods: (1) it only takes advantage of the presence of phenol-red, a
      normal cell medium component, with no need of addition of extraneous substances;
      (2) it is a very mild treatment virtually suitable for any cell type and (3) it
      allows transfection of selected cells even in the presence of cells of different
      type (providing that they are morphologically distinguishable).

PMID- 8988609
TI  - Virucidal activity of pure singlet oxygen generated by thermolysis of a water
      soluble naphthalene endoperoxide.
AB  - Using the water-soluble naphthalene carrier of singlet oxygen NDPO2, we have
      shown that pure singlet oxygen is able to inactivate enveloped viruses (human
      immunodeficiency virus type 1, herpes simplex virus type 1, cytomegalovirus,
      vesicular stomatitis virus), but has no effect on non-enveloped viruses
      (adenovirus and poliovirus 1). These results are related to the experiments on
      photoinactivation of viruses by hydrophobic photosensitizers (merocyanine 540,
      hypericin, phthalocyanines, hematoporphyrin and benzoporphyrin derivatives) and
      they strengthen the hypothesis that singlet oxygen plays a predominant role in
      this process.

PMID- 8988611
TI  - A mutant of Escherichia coli hyper-resistant to a number of DNA damaging agents:
      location of the mutational site.
AB  - A mutant of Escherichia coli, isolated as hyper-resistant to UVC, is found to be
      hyper-resistant to UVA, H2O2, low concentrations of nalidixic acid, novobiocin,
      UVA plus H2O2 and UVA plus 8-methoxypsoralen. A mutational site (uvh) conferring
      the hyper-resistance phenotype to UVC, and presumably to other DNA damaging
      agents, has been mapped at the 89.9 min region on the chromosome. Complementation
      analysis with an F-prime uvh+/uvh- diploid strain showed that the uvh+ allele is
      dominant over uvh- in trans. Studies with a variety of plasmids, carrying various
      LexA regions, introduced into the UV hyper-resistant strain show that mutation at
      the uvh locus may be responsible for derepression of the SOS inducible repair
      system. Based on the results, it is suggested that uvh is a part of the SOS
      inducible system. A plausible explanation for the hyper-resistance phenotypes for
      various DNA damaging agents and a model for the genetic control of a second set
      of putative SOS regulons are presented.

PMID- 8988612
TI  - UVB irradiation-induced transcription from the long terminal repeat of
      intracisternal A particles and UVB-induced secretion of an extracellular factor
      that induces transcription of the intracisternal A particles in unirradiated
      cells.
AB  - Intracisternal A particles (IAPs) are endogenous defective retroviral-like
      elements encoded by a family of proviral sequences present as a thousand copies
      in the mouse genome. In order to analyse the regulation of the long terminal
      repeat (LTR) directed transcription by UVB, D152 murine cells were transfected
      with a chimeric construct carrying the LTR of IAP linked to the bacterial
      chloramphenicol-acetyl-transferase reporter gene and then subjected by UVB
      irradiation in a dose- and time-dependent manner. Like the human immunodeficiency
      virus 1 type LTR and in spite of the lack of the nuclear factor kappa B consensus
      sequence, the IAP LTR could be activated by UVB. In addition, the D152 cells
      produced an extracellular factor are factors in response to UVB irradiation which
      activated the IAP LTR in unirradiated cells. This factor was detected both when
      responding cells were cocultured with inducing cells and when conditioned medium
      from irradiated cultures was added to the cell cultures.

PMID- 8988613
TI  - Photoinduced electron transfer from nucleotides to DNA intercalating viologens. A
      study by laser-flash photolysis and spectroelectrochemistry.
AB  - Fluorescent DNA-binding N,N'-dialkyl 6-(2-pyridinium)phenanthridinium dications
      (where dialkyl stands for -(CH2)2-or-(CH2)3-, abbreviated dq2pyp and dq3pyp,
      respectively) associate with GMP (guanosine-5'-monophosphate) in 0.1-mol l-1, pH
      3.5-5.5, phosphate buffer solution to yield 1:1 and 1:2 non-emissive complexes,
      the formation constants of which range from 197-63 and 19-11 l mol-1,
      respectively. In addition to the strong static quenching, dynamic deactivation of
      their excited state occurs at diffusion-controlled rate ki = 5.2 x 10(9) l mol-1
      s-1). Illumination of the GMP-containing solutions of the dyes with a 355 nm
      laser pulse produces a transient, with strong absorbance at 510 and 720 nm for
      dq2pyp, and 420 and 560 nm for dq3pyp. An identical transient is produced in the
      presence of ascorbic acid instead of the mononucleotide. By comparison to the
      electrochemically generated absorption spectra of the monoreduced dyes, the
      photogenerated transients have been assigned unequivocally to their corresponding
      radical-cations, formed by electron transfer to the anglet excited state. The
      back redox reaction between the oxidized quencher and dq2pyp+ proceeds at a rate
      of 1-2 x 10(9) l mol-1 s-1. The same transient has been observed also for the DNA
      intercalated viologens; this result, together with the little ability of these
      dyes to sensitize the formation of singlet dioxygen or to produce superoxide
      anion, demonstrate that their DNA photocleavaging activity is initiated by an
      efficient light-induced electron transfer from the nucleobases.

PMID- 8988614
TI  - Biologically weighted personal UV dosimetry.
AB  - People are exposed to natural or artificial UV radiation in different ways;
      unintentionally or intentionally, at their workplace on their spare time. To
      quantify the amount of individual UV exposure, a personal dosimetry is necessary.
      In research, polysulphone film (PSF) dosimeters are the most frequently used
      personal UV dosimeters. We use calculated weighting factors in the measurement
      processing of polysulphone film dosimeters. The special weighting factor
      transforms the dosimeter reading from an equivalent UV dose to the biologically
      effective UV dose. The factor depends on the investigated problem (action
      spectrum of the photobiological effect and spectral distribution of the incident
      UV source), the calibration of PSF was carried out once by a monochromatic
      radiation (gamma = 295 nm). The equivalent dose readings are available from this
      calibration curve for any investigated question. A presented result of this
      method is the seasonal measurement of erythemally effective UV exposure by
      ambient solar radiation, and the individual exposure level in a "normal" person
      concerning UV exposure and also in groups with the risk of a lack of sunshine.
      Further applications are occupational measurements of the risk of health damage
      by UV radiation (with respect to the limit of the maximum permissible 8 h
      exposure according to IRPA/INIRC-guidelines). We controlled the extent of UV
      exposure in workers in the area of arc welding workplaces. The biological
      weighting of PSF readings simplifies a routine use of PSF in personal UV
      monitoring to investigators without the expending special measurement technology
      (e.g. spectroradiometer).

PMID- 8988616
TI  - Equivalent background speed in recovery from motion adaptation.
AB  - We measured, in the same observers, (1) the detectability, d, of a small
      rotational jump following adaptation to rotational motion and (2) the
      detectability of the same jump when superimposed on one of several background
      rotation speeds. Following 90 s of motion adaptation the detectability of the
      jump was impaired, and sensitivity slowly recovered over the course of 60 s. The
      detectability of the jump was also impaired by the background speed in a way
      consistent with a quadratic form of Weber's law. We propose that motion
      adaptation impairs the detectability of the small jump because it is as if an
      equivalent background speed has been superimposed on the display. We measured the
      equivalent background by finding the real background speed that produced the same
      d' at each instant in the recovery from motion adaptation. The equivalent
      background started at approximately one to two thirds the speed of the adapting
      motion, declined rapidly, rose to a small peak at 30 s, then disappeared by 60 s.
      Since the equivalent background speed corresponds to the speed of the motion
      aftereffect, we have measured the time course of the motion aftereffect with
      objective psychophysics.

PMID- 8988615
TI  - How big is a Gabor patch, and why should we care?
AB  - We propose a two-parameter model for the perceived size (spatial extent) of a
      Gaussian-windowed, drifting sinusoidal luminance pattern (a Gabor patch) based on
      the simple assumption that perceived size is determined by detection threshold
      for the sinusoidal carrier. Psychophysical measures of perceived size vary with
      peak contrast, Gaussian standard deviation, and carrier spatial frequency in a
      manner predicted by the model. At suprathreshold peak contrasts Gabor perceived
      size is relatively unaffected by systemic noise but varies in a manner that is
      consistent with the influence of local contrast gain control. However, at and
      near threshold, systemic noise plays a major role in determining perceived size.
      The data and the model indicate that measures of contrast threshold using
      Gaussian-windowed stimuli (or any other nonflat contrast window) are determined
      not just by contrast response of the neurons activated by the stimulus but also
      by integration of that activation over a noisy, contrast-dependent extent of the
      stimulus in space and time. Thus, when we wish to measure precisely the influence
      of spatial and temporal integration on threshold, we cannot do so by combining
      contrast threshold measures with Gaussian-windowed stimuli.

PMID- 8988617
TI  - Photon migration of near-diffusive photons in turbid media: a Lagrangian-based
      approach.
AB  - We show that light transport in a turbid medium can be described by a path
      integral with a quasi-particle Lagrangian. The most probable trajectory over
      which photons can be found can be obtained from this Lagrangian. This approach
      extends the diffusion approximation to the near-diffusive regime, in which
      photons travel only a few transport mean free paths.

PMID- 8988618
TI  - Improved solutions of the steady-state and the time-resolved diffusion equations
      for reflectance from a semi-infinite turbid medium.
AB  - Improved solutions of the diffusion equation for time-resolved and steady-state
      spatially resolved reflectance are investigated for the determination of the
      optical coefficients of semi-infinite turbid media such as tissue. These
      solutions are derived for different boundary conditions at the turbid-medium-air
      interface and are compared with Monte Carlo simulations. Relative reflectance
      data are fitted in the time domain, whereas relative and absolute reflectance are
      investigated in the steady-state domain. It is shown that the error in deriving
      the optical coefficients is, especially for steady-state spatially resolved
      reflectance, considerably smaller for the solutions under study than for the
      commonly used solutions. Analysis of experimental measurements of absolute steady
      state spatially resolved reflectance confirms these results.

PMID- 8988619
TI  - Perturbation theory for diffuse light transport in complex biological tissues.
AB  - A perturbation theory for the forward problem of optical transport in turbid
      media is developed. It is applicable to media with scattering and absorption in
      homogeneties and steady-state and modulated light. Absorbing perturbations can be
      described by a volume distribution of virtual sources that primarily causes a
      monopole perturbation light field. Scattering objects have an additional
      contribution that, in the limiting case of sharply bounded objects, is
      represented by a surface distribution of virtual sources and causes a dipolelike
      perturbation pattern. Using the concept of virtual sources, we discuss a possible
      ambiguity between the perturbations from scattering and absorbing inhomogeneities
      and the implications for the source-detector placement in inverse problems. We
      show that the surface effects due to sharp boundaries of scattering objects pose
      both a numerical problem and a chance to improve the resolution of inverse
      algorithms.

PMID- 8988620
TI  - Convolution picture of the boundary conditions in photon migration and its
      implications in time-resolved optical imaging of biological tissues.
AB  - To model the effect of a tissue-air boundary on time-resolved optical
      measurements, a convolution picture is presented based on the photon migration
      picture. It is demonstrated that the boundary conditions (either index matched or
      index mismatched) can be formulated as a spatiotemporal convolution of two terms,
      with the first being identical to the solution in the infinite medium and the
      second being independent of the original light source. The conditions under which
      the spatial convolution part in the second term becomes negligible are also
      determined thus permitting the complete separation of the two terms by use of a
      temporal Laplace or Fourier transformation. This result is promising, since it,
      suggests a method of removing the effect of the boundary conditions in the
      applications of time-resolved optical imaging (in both the time domain and the
      frequency domain) in biological tissues.

PMID- 8988621
TI  - Luminescence optical tomography of dense scattering media.
AB  - Using a set of coupled radiation transport equations, we derive image operators
      for luminescence optical tomography with which it is possible to reconstruct
      concentration and mean lifetime distribution from information obtained from dc
      and time-harmonic optical sources. Weight functions and detector readings were
      computed from analytic solutions of the diffusion equation and from numerical
      solutions of the transport equation by Monte Carlo methods. Detector readings
      were also obtained from experiments on vessels containing a balloon filled with
      dye embedded in an Intralipid suspension with dye in the background. Image
      reconstructions were performed by the conjugate gradient descent method and the
      simultaneous algebraic reconstruction technique with a positivity constraint. A
      concentration correction was developed in which the reconstructed concentration
      information is used in the mean-lifetime reconstruction. The results show that
      the target can be accurately located in both the simulated and the experimental
      cases, but quantitative inaccuracies are present. Observed errors include a
      shadowing effect in regions that have the lowest weight within the inclusion.
      Application of the concentration correction can significantly improve
      computational efficiency and reduce error in the mean-lifetime reconstructions.

PMID- 8988622
TI  - Imaging objects in tissuelike media with optical tagging and the diffuse photon
      differential transmittance.
AB  - In a proof-of-concept experiment, we optically tagged objects embedded in an
      inhomogeneous and multiple-scattering medium and measured the difference between
      the transmitted diffuse photons at two optical wave-lengths, one at and the other
      off a sharp absorption peak of the exogenous contrast agent. We demonstrated that
      the visibility of tagged objects was significantly enhanced in comparison with
      that of untagged objects. From our analysis it seems possible to use dual
      wavelength differential transmittance spectrometry together with monoclonal
      antibody-delivered optical contrast agents to detect tumors as small as 0.1-0.3
      cm in size and embedded as deeply as a few centimeters beneath a tissue surface.

PMID- 8988623
TI  - Regularized progressive expansion algorithm for recovery of scattering media from
      time-resolved data.
AB  - Reconstructions of the absorption cross sections of dense scattering media from
      time-resolved data are presented. A progressive expansion (PE) algorithm, similar
      to a layer-stripping, is developed to circumvent the underdeterminedness of the
      inverse problem. An overlapping scheme, which used detector readings from several
      consecutive time intervals, is introduced to reduce the propagation of
      reconstruction errors that occur at shallower depths. To reduce the sensitivity
      of the PE algorithm to noise a regularized progressive expansion (RPE) algorithm
      is proposed, which incorporates regularization techniques into the PE algorithm.
      The PE and the RPE algorithms are applied to the problem of image reconstruction
      from time-resolved data. The test media were isotropically scattering slabs
      containing one or two compact absorbers at different depths below the surface.
      The data were corrupted by additive white Gaussian noise with various strengths.
      The reconstruction results show that the PE and the RPE algorithms, when they are
      combined by proper overlapping, can effectively overcome the underdeterminedness
      of the inverse problem. The RPE algorithm yields reconstructions that are more
      accurate and more stable under the same noise level.

PMID- 8988624
TI  - Frequency-domain optical imaging of absorption and scattering distributions by a
      Born iterative method.
AB  - We presents a Born; iterative method, for reconstructing optical properties of
      turbid media by means of frequency-domain data. The approach is based on
      iterative solution of a linear perturbation equation, which is derived from the
      integral from of the Helmholtz wave equation for photon-density waves in each
      iteration the total field and the associated weight matrix are recalculated based
      on the previous reconstructed image. We then obtain a new estimate by solving the
      updated perturbation equation. The forward solution, also based on a Helmholtz
      equation, is obtained by a multigrid finite difference method. The inversion is
      carried out through a Tikhonov regularized optimization process by the conjugate
      gradient descent method. Using this method, we first reconstruct the distribution
      of the complex wave numbers in a test medium, from which the absorption and the
      scattering distributions are then derived. Simulation results with two
      dimensional test media have shown that this method can yield quantitatively (in
      terms of coefficient valued) as well as qualitatively (in terms of object
      location and shape) accurate reconstructions of absorption and scattering
      distributions in cases in which the first-order Born approximation cannot work
      well. Both full-angle and limited-angle measurement schemes have been simulated
      to examine the effect of the location of detectors and sources. The robustness of
      the algorithm to noise has also been evaluated.

PMID- 8988625
TI  - Comparison of the response of serum ceruloplasmin and cholesterol, and of tissue
      ascorbic acid, metallothionein, and nonprotein sulfhydryl in rats to the dietary
      level of cystine and cysteine.
AB  - The effects were compared of the addition of graded levels of L-cystine and of L
      cysteine (0.3, 3, or 5%) to a 10% casein diet on several metabolic parameters in
      rats. The growth-promoting effect of cystine was equivalent to that of cysteine.
      Supplementation of these two amino acids elevated serum cholesterol, liver
      ascorbic acid, liver nonprotein sulfhydryl (SH) and kidney metallothionein, and
      reduced the activity of serum ceruloplasmin. The responses of serum cholesterol,
      liver nonprotein SH, and serum ceruloplasmin to cystine were greater than of
      those to cysteine. When the basal diet was supplemented with 0.3% of these amino
      acids, the elevation of liver ascorbic acid by cystine supplementation was less
      than that by cysteine supplementation. However, when supplemented with 5% of
      these amino acids, the elevation of liver ascorbic acid by cystine was greater
      than that by cysteine. There was no difference in the influence of cystine and
      cysteine on kidney metallothionein. This study demonstrates that dietary cystine
      and cysteine had the same influence on growth, but had a differential influence
      on such metabolic parameters as liver nonprotein SH, serum ceruloplasmin, serum
      cholesterol, and tissue ascorbic acid.

PMID- 8988626
TI  - Characterization of the bovine kappa-casein gene promoter.
AB  - kappa-Casein gene promoter was localized within a 570-bp fragment (-552/+18) of a
      5'-flanking region by the gene transfection assay. Deletion mutation analysis in
      mammary epithelial cell line, HC11, suggested that there are regulatory element
      in a region from -439 through -125. Some nuclear proteins from lactating rate
      mammary gland bind to this region specifically. One of them expressed
      preferentially during pregnancy bound to a 132-bp fragment (-439/-308) and
      another expressed preferentially during lactation bound to a 183-bp fragment (
      307/-125).

PMID- 8988627
TI  - Xyloglucan endotransglycosylation in suspension-cultured poplar cells.
AB  - Xyloglucan endotransglycosylase activity was identified and defined by transfer
      of a part of xyloglucan to reduced xyloglucan heptasaccharide ([3H]XXXGol) in an
      enzyme preparations from suspension-cultured poplar cells. Although the activity
      was distributed in buffer-soluble and buffer-insoluble fractions associated with
      cells and in the extracellular fraction, it was mostly recovered in the buffer
      insoluble fraction, suggesting that the enzyme was bound to the cell wall. The
      affinity for acceptor XXXGol was increased at a higher concentration of donor
      xyloglucan with a constant Vmax. The Vmax for donor xyloglucan was increased at a
      higher concentration of the oligosaccharide without any change in affinity. These
      kinetic data suggest that the acceptor acts by combining with the enzyme
      independently of the donor. The velocity of the reaction decreased gradually as
      the heptasaccharide units was increased from two to four, suggesting that the
      xyloglucan endotransglycosylase reaction caused donor xyloglucan substantially to
      decrease in molecular size. The activity in buffer-soluble fraction was increased
      by ABA in auxin-starved cells, when cultured in MS medium containing various
      plant hormones. Nevertheless, the activity increased markedly at the exponential
      growth and decreased immediately at the stationary phase of cells in the presence
      of 2,4-D. The activity of xyloglucan endotransglycosylase is developmentally
      regulated during the growth but is not directly induced by plant hormones.

PMID- 8988628
TI  - Three extracellular chitinases in suspension-cultured rice cells elicited by N
      acetylchitooligosaccharides.
AB  - In rice suspension culture, a large part (about 90% of total activity in the
      culture) of the chitinase activity was found in the medium. Two extracellular
      chitinases (which we named RCH-A and -B) were separated from the cell suspension
      by DEAE-cellulofine column chromatography. When cells were treated with N
      acetylchitooligosaccharides (chitin oligosaccharides) for 3 days, extracellular
      chitinase activity increased about 3-fold over the control culture. After the
      treatment, another extracellular chitinase (named RCH-C) appeared in addition to
      increases in the levels of RCH-A and -B. Partial amino acid sequences of these
      enzymes indicated that RCH-A (33.5 kDa) and -B (34 kDa) were class Ib chitinases
      but RCH-C (27 kDa) was a class III chitinase. RCH-A and -B were capable of
      actively degrading water-insoluble chitin with high affinities, while RCH-C had
      less affinity for the substrate. However, when a water-soluble chitin derivative,
      6-O-hydroxyethylchitin (glycolchitin) was used, RCH-C as well as RCH-A and -B
      degraded actively with a high affinity. A synergistic effect was observed when
      these three chitinases acted simultaneously in the hydrolysis of chitin.

PMID- 8988629
TI  - Ginsenosides increase secretion of lipoprotein lipase by 3T3-L1 adipocytes.
AB  - Treatment of 3T3-L1 adipocytes with either an oleanolic acid glycoside or a 20(S)
      protopanaxatriol glycoside increased the secretion of lipoprotein lipase activity
      into the medium dose-dependently. At a concentration of 100 micrograms/ml,
      ginsenosides Ro, Re, Rg1, and Rh1 increased the secretion of lipase activity into
      the medium by 119, 107, 56, and 32%, respectively. The ratio of lipase activity
      in the medium to cellular lipase activity was 4.7% in control cells and 8.6% in
      ginsenoside Ro-treated cells, 8.3% in ginsenoside Re-treated cells, 7.0% in
      ginsenoside Rg1-treated cells, and 6.3% in ginsenoside Rh1-treated cells.
      Ginsenoside Rb2, which is a 20(S)-protopanaxadiol glycoside, increased the
      secretion of lipase activity by 16% at 25 micrograms/ml, and the ratio of lipase
      activity in the medium to cellular lipase activity was higher in ginsenoside Rb2
      treated cells than in control cells. However, at 100 and 200 micrograms/ml,
      ginsenoside Rb2 decreased the secretion of lipase activity in parallel with
      cellular lipase activity. Ginsenoside Rd also decreased the secretion of lipase
      activity in the same dose-dependent manner. Thus, the effective dose for the
      secretion of lipoprotein lipase activity with ginsenosides varies with their
      aglycone structure.

PMID- 8988630
TI  - Effects of ganglioside GD1a on the fluidity and phase transition of
      phosphatidylcholine model membrane immobilized on porous cellulose acetate
      filter.
AB  - The thermotropic effect of ganglioside GD1a on the phosphatidylcholine membrane
      immobilized on the porous cellulose acetate filter was investigated by ESR spin
      labeling and DSC. The spin-labeled GD1a having 12-DOXYL-stearic acid instead of
      the long acyl chain of the ceramide portion (GD1a*) was incorporated into the
      model membrane. An ESR examination of the membrane showed that GD1a* undergoes an
      anisotropic rotation in the wide range of temperature -30-70 degrees C. By
      monitoring the overall splitting (2T parallel) of spin-labeled
      phosphatidylcholine (PC*), the model membranes were found to show decreased
      fluidity in accordance with the GD1a content. The phase transition temperature
      (Tm) of distealoylphosphatidylcholine (DSPC) model membranes could be estimated
      by the measurement of ESR and DSC. The effects of GD1a were found to be more
      significant in broadening the phase transition rather than in elevating the Tm of
      DSPC model membranes.

PMID- 8988631
TI  - Base specificity and primary structure of poly U-preferential ribonuclease from
      chicken liver.
AB  - The primary structure and base specificity of chicken liver RNase CL1 which has
      been reported by Miura et al. [Chem. Pharm. Bull., 32, 4053-4060 (1984)] as poly
      U-preferential RNase, were extensively studied. The sequence study of this enzyme
      and comparison of the amino acid sequence of the enzyme with homologous RNases
      from oyster and Drosophila melanogaster suggested that RNase CL1 consists of
      three peptides with 17, 19, and 163 amino acid residues. The amino acid sequence
      of these three peptides were identified. The two small peptides are joined to the
      large peptide by disulfide bridges. The amino acid sequence of RNase CL1 had 62
      (31.2%) and 63 residues (31.6%) identical with oyster RNase and D. melanogaster
      RNase, respectively, and belongs to the RNase T2 family RNase. Reassessment of
      the base specificity of RNase CL1 found that it is guanylic acid, then uridylic
      acid-preferential, and not poly U preferential.

PMID- 8988632
TI  - Cytotoxicity of 7-ketocholesterol toward cultured rat hepatocytes and the effect
      of vitamin E.
AB  - The effects of 7-ketocholesterol on rat hepatocytes prepared by collagenase
      perfusion were examined. The viability of cells incubated with 100 microM 7
      ketocholesterol was significantly lower than those with cholesterol, although the
      LDH activity in the cultured medium remained unchanged during the incubation.
      Hepatocytes treated with 7-ketocholesterol produced large amounts of .NO and O2-
      in the early stage of incubation. Treatment of the hepatocytes with Carboxy-PTIO,
      which selectively scavenged .NO, or with L-NMMA, an inhibitor of .NO synthase,
      increased the cell viability. The addition of 7-ketocholesterol to the culture
      medium tended to increase the ratio of total sterol to phospholipid of the
      hepatocytes in a time-dependent manner without changing the content of
      phospholipid. No lipid peroxidation or oxidation of the cellular SH groups,
      protein SH and glutathione, was apparent. Vitamin E added 1 h before the addition
      of 7-ketocholesterol prevented the hepatocytes from cell death by suppressing the
      incorporation of 7-ketocholesterol into the hepatocytes and by scavenging O2-.

PMID- 8988633
TI  - Cloning and nucleotide sequence of the beta-D-glucosidase gene from
      Bifidobacterium breve clb, and expression of beta-D-glucosidase activity in
      Escherichia coli.
AB  - Genomic DNA encoding a beta-D-glucosidase (EC 3.2.1.21), which has beta-D
      fucosidase activity, was cloned from Bifidobacterium breve clb. We sequenced a
      1.9-kbp cloned DNA fragment that contained a single open reading frame encoding
      460 amino acids with a calculated molecular mass of 51,513 Da. A putative
      ribosome binding site was found 5 bp upstream of the initiation codon. The amino
      acid sequence of this beta-D-glucosidase from Bifidobacterium breve clb had 46%
      identity with that of beta-glucosidase from Microbispore bispore. The enzyme of
      Bifidobacterium breve clb was expressed in Escherichia coli. A cell-free extract
      prepared from the recombinant strain showed 80 to 90-fold more beta-D-glucosidase
      activity than that from Bifidobacterium breve clb. The recombinant enzyme was
      purified to homogeneity from cell-free extracts of the recombinant strain using 4
      column chromatographies. The recovery of enzyme from the recombinant strain was
      about 138-fold-higher than that of Bifidobacterium breve clb. The enzymatic
      properties were similar to those of Bifidobacterium breve clb. For application of
      this recombinant enzyme, we attempted to synthesize a disaccharide that seemed to
      be specifically assimilated by Bifidobacteria using the condensation activity of
      the enzyme.

PMID- 8988634
TI  - In vitro survey of alpha-glucosidase inhibitory food components.
AB  - A survey of food components with alpha-glucosidase (AGH) inhibitory activity was
      conducted to identify a prophylactic effect for diabetes in food. Sardine muscle
      hydrolyzed by alkaline protease showed potent activity (IC50 = 48.7 mg/ml) as
      well as green and oolong teas (IC50 = 11.1 and 11.3 mg/ml, respectively).
      Furthermore, hydrolyzates prepared by various proteases gave differing AGH
      inhibitory activity. DEAE-Sephadex chromatography of the alkaline protease
      hydrolyzate eluted potent AGH inhibitors (IC50 = 15.6 mg/ml) with a 50 mM
      phosphate buffer (pH 7.0) containing 0.3 M NaCl, and their subsequent separation
      by HPLC in an ODS column showed that there were some inhibitors possessing
      primary amino groups. This indicates that they would have been high anionic and
      peptidic compounds.

PMID- 8988636
TI  - 3-Hydroxyisobutyrate dehydrogenase from Pseudomonas putida E23: purification and
      characterization.
AB  - The NAD(+)-dependent 3-hydroxyisobutyrate dehydrogenase [EC 1.1.1.31] was
      purified to homogeneity from Pseudomonas putida E23. The enzyme was a tetramer
      (molecular mass, 120 kDa) consisted of identical subunits (molecular mass, 30
      kDa). The enzyme was specific for NAD+ (Km, 0.44 mM). The maximal activity was
      obtained at about pH 10. The enzyme was specific for the L-isomer of 3
      hydroxyisobutyrate. In addition to L-3-hydroxyisobutyrate, L-serine, 2-methyl-DL
      serine, and 3-hydroxypropionate were substrates. The Km for L-3
      hydroxyisobutyrate, L-serine, 2-methyl-DL-serine, and 3-hydroxypropionate were
      0.12, 18, 44, and 83 mM, respectively. The enzyme was inhibited by p
      chloromercuribenzoate, HgCl2, and AgNO3, but not by EDTA, alpha,alpha'-dipyridyl,
      and o-phenanthroline. The N-terminal 26 amino acid sequence was compared with the
      sequences deduced from the enzyme genes of rat liver and Pseudomonas aeruginosa.

PMID- 8988635
TI  - Dipeptidyl aminopeptidase IV from Pseudomonas sp. WO24.
AB  - Dipeptidyl aminopeptidase IV from Pseudomonas sp. WO24 was purified as two
      molecular forms of 84 and 82-kDa by SDS-PAGE. Peptide mapping and N-terminal
      sequence analyses indicated that both proteins might be derived from the same
      protein, and that the 82-kDa molecule might be a truncated form from the 84-kDa
      molecule at least at the N-terminus. The DAP IV gene of Pseudomonas sp. WO24 was
      cloned and expressed in E. coli. The enzyme expressed in E. coli JM109 harboring
      a hybrid plasmid, pYO-6A, with about a 3-kbp fragment containing the DAP IV gene,
      was purified with an activity recovery of 24%. The recombinant enzyme also had
      the same two molecular forms, though the ratio of the two forms (about 1:1) was
      different from that of the native ones (about 1:4). The native and recombinant
      enzyme preparations had similar specific activities, suggesting that the 84 and
      82-kDa molecules are in an active form and have almost the same specific
      activity. The molecular mass, the subunit number, the substrate specificity, and
      the effects of various inhibitors of the native enzyme indicated that this enzyme
      was a typical DAP IV and had properties similar to those of Flavobacterium
      meningosepticum rather than others.

PMID- 8988637
TI  - Purification and characterization of a lectin from Amaranthus hypochondriacus
      var. Mexico seeds.
AB  - A lectin from Amaranthus hypochondriacus var. Mexico (AHML) was purified by
      affinity chromatography using asialofetuin-Sepharose 4B. AHML is specific for N
      acetyl-D-galactosamine as are the other Amaranthus lectins. AHML has no
      carbohydrate moiety and requires no metal ion for the hemagglutination activity.
      The pI of AHML is 6.8. AHML has a native molecular mass of 45.0 kDa and is
      composed of homo-subunits having molecular masses of 36.8 kDa.

PMID- 8988638
TI  - Steady-state kinetic and calorimetric studies on the binding of Aspergillus niger
      glucoamylase with gluconolactone, 1-deoxynojirimycin, and beta-cyclodextrin.
AB  - Binding equilibria of Aspergillus niger glucoamylase with its several ligands
      were observed to analyze the binding modes of the ligands. Steady-state kinetic
      studies using p-nitrophenyl alpha-glucoside as a substrate showed that 1
      deoxynojirimycin, which is a mixed type inhibitor for Rhizopus glucoamylase, was
      a competitive type inhibitor bound at the active site of the enzyme, but
      gluconolactone, which is also a mixed type inhibitor for Rhizopus glucoamylase,
      was a non-competitive type inhibitor forming a nonproductive ternary complex with
      the enzyme and the substrate. beta-Cyclodextrin, which binds to the starch
      binding domain of the enzyme, did not inhibit the enzyme activity, showing that
      there was no interaction between the catalytic domain and the starch-binding
      domain for the binding of the substrate and beta-cyclodextrin. Isothermal
      titration calorimetry showed that one 1-deoxynojirimycin molecule and two beta
      cyclodextrin molecules bind to the catalytic domain and the starch-binding domain
      of the enzyme, respectively, and there is no significant interaction between the
      binding of these ligands.

PMID- 8988639
TI  - Efficient lipase-catalyzed preparation of long-chain fatty acid esters of bile
      acids: biological activity and synthetic application of the products.
AB  - A highly regioselective (3-position) and efficient (quantitative yield) acylation
      of bile acids catalyzed by immobilized Candida antarctica lipase was established.
      Methyl cholate derivatives acylated with long-chain fatty acids (C12-C16) showed
      an inhibitory effect on the growth of some strains of Gram-positive and -negative
      bacteria (27-400 micrograms/ml). The anti-bacterial activity was slightly weaker
      than has been observed for methyl cholate, while the increased lipophilicity and
      lower melting points of the present derivatives are well suited for a potential
      germicide which would be safe and be topically applied. This enzyme-catalyzed
      transesterification is also demonstrated as an expeditious route to
      ursodeoxycholic acid, in respect of the regioselective introduction of acyl
      protecting groups on the hydroxyl groups of the intermediates. 7-Ketolithocholic
      acid, a known direct precursor of ursodeoxycholic acid, was obtained from cholic
      acid via chenodeoxycholic acid in a 46% yield and 9 steps.

PMID- 8988640
TI  - Analysis of (-)-epigallocatechin gallate in human serum obtained after ingesting
      green tea.
AB  - A method for analyzing the EGCg concentration in human serum was developed by
      using high-performance liquid chromatography with electrochemical detection. EGCg
      was detected in human serum after the ingestion of 5 g of green tea powder (matsu
      cha) dissolved in 200 ml of hot water. The concentration of EGCg in the serum
      reached the highest level about 2 h after ingesting the green tea, and then
      decreased.

PMID- 8988641
TI  - Isolation and characterization of a plasmid from Lactobacillus helveticus CP53.
AB  - A plasmid, pCP53 (11.5 kilo base pairs long), was isolated from Lactobacillus
      helveticus CP53 and its restriction map was constructed. A chimeric plasmid,
      pCP53D (4.7 kb), which had a 2.0-kb HindIII fragment from pCP53 and a
      tetracycline resistance (Tc) gene from Streptococcus faecalis replicated and
      expressed tetracycline resistance in Lactobacillus casei CP680. Fifteen strains
      of L. helveticus were transformed with pCP53D by electroporation and selected for
      Tc resistance. Transformants were obtained from two out of 15 host strains, L.
      helveticus CP611 and CP791, with 5 x 10(3) and 50 transformants per microgram of
      DNA, respectively.

PMID- 8988642
TI  - Effect of sesamin on the composition of eicosapentaenoic acid in liver and on its
      lymphatic absorption in rats.
AB  - Changes in the hepatic concentration of n-3 fatty acids, e.g., eicosapentaenoic
      acid and linolenic acid, were significantly reduced by their simultaneous
      administration with sesamin, whereas there was no such effect of sesamin for n-6
      and n-9 fatty acids. However, there was no significant difference in lymphatic
      absorption between eicosapentaenoic acid (n-3) and arachidonic acid (n-6),
      irrespective of the presence of absence of sesamin.

PMID- 8988643
TI  - Transduction of a cosmid with the R4 phage cos sequence by heterogeneous
      actinophages, SPA10 and SPA38.
AB  - A cosmid, pR4C1, composed of the actinophage R4 cos sequence and Streptomyces
      plasmid pIJ365, was encapsidated in R4 phage particles in vivo. [T. Morino et
      al., Mol. Gen. Genet., 198, 228-233 (1985)] In this report a cosmid derivative,
      pR4C4, is shown to be also encapsidated by heterogeneous actinophages, SPA10 and
      SPA38, and transferred to Streptomyces lividans. Use of this transduction and
      conservation of the DNA packaging mechanism are discussed.

PMID- 8988644
TI  - Inhibitory effect of dietary wheat bran on formation of aberrant crypt foci in
      rat colon induced by a single injection of 1,2-dimethylhydrazine.
AB  - The frequency of appearance of aberrant crypt foci (ACF) in the distal colon was
      significantly lower in rats fed a high fiber (20% wheat bran) diet than in those
      fed a fiber-free one at 4 weeks after a single injection of 1,2-dimethylhydrazine
      (DMH, 20 mg/kg), although crypt/ACF was high in the former relative to the
      latter. This result suggests that dietary wheat bran effectively serves as a
      regulator of ACF frequency at early stages after DMH injection.

PMID- 8988645
TI  - Antimutagenic effects of ajoene, an organosulfur compound derived from garlic.
AB  - The antimutagenic effects of ajoene, which is an organosulfur compound derived
      from garlic, were investigated by the Ames test. Ajoene inhibited mutagenesis
      induced by both benzo[a]pyrene (B[a]P) and 4-nitro-1,2-phenylenediamine (NPD) in
      a dose-dependent manner. In particular, NPD-induced mutagenesis was more
      effectively suppressed by ajoene than the B[a]P-induced type. Furthermore, the
      inhibition of mutagenesis by ajoene was more effective for transition-type
      mutations than for the frame shift type. HPLC analysis of B[a]P metabolism in the
      presence of the rat liver microsomal fraction (S-9) showed that ajoene dose
      dependently inhibited the metabolic activation of B[a]P. This suggests that
      ajoene affected the metabolic enzymes in the S-9 fraction.

PMID- 8988646
TI  - Bacterial production and purification of phosphorylatable phosphoenolpyruvate
      carboxylase from tobacco.
AB  - Tobacco phosphoenolpyruvate carboxylase (PEPC) [EC 4.1.1.31] cDNA was efficiently
      expressed in E. coli under the control of the lacZ promoter. The enzyme, purified
      to homogeneity, had the same catalytic activity, and was phosphorylated in vitro
      by maize PEPC kinase.

PMID- 8988647
TI  - Preparation and some properties of type I collagen from fish scales.
AB  - Soluble collagen from fish (sardine) scales was yielded at about 5% with 0.5 M
      acetic acid after demineralization with EDTA, while a great portion of the
      collagen remained insoluble. The solubility of this insoluble collagen was about
      20% at 45 degrees C (denaturation temperature of soluble collagen) for 24 h. The
      remaining 80% of the insoluble collagen was denatured in the form of insoluble
      gelatin, and that may be an interesting food material.

PMID- 8988648
TI  - N-linked sugar chain of 55-kDa royal jelly glycoprotein.
AB  - An N-linked sugar chain from 55-kDa royal jelly glycoprotein (RJGP), which
      maintains the high viability of rat liver primary cultured cell and is a
      different molecular species from 350-kDa RJGP [Kimura et al., Biosci. Biotech.
      Biochem., 59, 507-509 (1995)], has been identified. The sugar chains were
      released by hydrazinolysis followed by N-acetylation and pyridylamination. The
      structural analysis of the pyridylaminated sugar chain was done by a combination
      of sequential exo-mannosidase digestions, MALDI-TOF MS, and 500 MHz 1H-NMR. For
      the carbohydrate moiety of 55-kDa RJGP, only one N-linked sugar chain has been
      detected. The structure has been found to be Man alpha 1-->2Man alpha 1-->6(Man
      alpha 1--> 2Man alpha 1-->3)Man alpha 1-->6(Man alpha 1-->2Man alpha 1-->2Man
      alpha 1-->3)Man beta 1-->4GlcNAc beta 1-->4GlcNAc, which is a non-processed high
      mannose type structure.

PMID- 8988649
TI  - Expression, purification and crystallization of a cohesin domain from the
      cellulosome of Clostridium thermocellum.
AB  - The cellulosome of the cellulolytic bacterium, Clostridium thermocellum, is a
      multi-enzyme complex in which the enzymatic (cellulolytic) subunits are attached
      to a unique nonhydrolytic subunit called scaffoldin. The attachment is mediated
      by two mutually interacting domains: namely multiple cohesin domains on the
      scaffoldin subunit and a dockerin domain on each of the enzymatic subunits.
      Knowledge of the three-dimensional structure of each of the interacting
      components would be critical to a better understanding of the cohesin-dockerin
      interaction at the molecular level. In this report, we describe the purification
      of one of the nine cohesin domains of the scaffoldin subunit from C.
      thermocellum. A DNA segment containing the cohesin 2 sequence was fused to a hexa
      histidine tag, and the resultant construct was expressed in Escherichia coli. The
      expressed peptide was efficiently isolated by metal-chelate affinity
      chromatography. The purified recombinant form of the cohesin was crystallized
      pending determination of its structure.

PMID- 8988651
TI  - Oil bioremediation using insoluble nitrogen source.
AB  - Oil bioremediation is limited by the availability of nitrogen and phosphorous,
      which are needed by the bacteria and not present in sufficient amounts in
      hydrocarbons. The supply of these two essential elements as water-soluble salts
      presents several problems. These include the rapid dilution of the salts in the
      large volumes of polluted land or water and their utilization by other bacteria
      that do not degrade oil. In addition, increasing the concentration of mobile
      nitrogen creates further environmental problems. The use of hydrophobic sources
      of nitrogen and phosphorous that have a low water solubility can overcome these
      problems. We have studied one such compound. F-1, that is not used by most
      bacteria but serves as a good nitrogen and phosphorous source for those bacterial
      strains that are capable of utilizing it. We have shown that bacteria using F-1
      do not cross-feed other bacterial strains. Moreover, when the concentration of
      the pollutant is sufficiently reduced, the multiplication of the bacteria slows
      down until they become a negligible fraction of the bacterial population.
      Chemical analysis indicated that following a 28-day treatment of Alaskan crude
      oil, most of the hydrocarbons, including polycyclic aromatics, are degraded to
      undetectable levels. The C34 and C35 components were also degraded, although
      their degradation was not completed within this time period. In treatment of a
      sandy beach that was accidentally polluted with crude heavy oil, about 90%
      degradation was obtained within about 4 months at an outside average temperature
      of 5 -10 degrees C.

PMID- 8988650
TI  - Overexpression and single-step purification of a thermostable xylanase from
      Bacillus stearothermophilus T-6.
AB  - Xylanase T-6 is a thermostable alkaline-tolerant enzyme that is produced by
      Bacillus stearothermophilus T-6. Xylanase T-6 was found to bleach pulp
      effectively at pH 9 and 65 degrees C and was used successfully on an industrial
      scale mill trial. To facilitate the future characterization of the protein via X
      ray analysis and protein engineering, it was necessary to overexpress the enzyme
      in Escherichia coli. The xylanase gene was cloned into T-7 polymerase expression
      vectors and its expression was optimized. The enzyme was found to constitute over
      70% of the cell protein and it was efficiently purified from the host proteins by
      a single heating step. Over 2 g soluble and active enzyme per 1 culture were
      achieved.

PMID- 8988652
TI  - Sol-gel applications in environmental biotechnology.
AB  - Sol gel process was applied for three different applications in environmental
      biotechnology: (1) thin, fluorescein diacetate-doped sol-gel film made possible
      epifluorescent microscopic examination of adsorbed Escherichia coli CN13 cells
      without additional staining: (2) Thiobacillus thiooxidans cell-free extract
      entrapped into sol-gel matrix displayed oxidative activity on H2S in liquid
      medium; and (3) two media (E. coli (EC) and sulfate-reducing bacteria (SRB)) were
      doped into sol-gel and used to enumerate environmental samples for E. coli and
      sulfate-reducing bacteria, by the most probable number (MPN) method. The
      comparison of the modified method with the standard enumeration method revealed
      very good correlation. The sol-gel MPN method is sensitive, saves times, and the
      substrate can be prepared and stored long-term at room temperature (up to 1
      year).

PMID- 8988653
TI  - Experimental study of ureteral free grafts. IV. Histomorphometric study.
AB  - OBJECTIVES: The ureteral changes that occur when rat ureter is used as an
      autologous free graft were evaluated using histomorphometrical methods. METHODS:
      The normal values were determined in ureters from normal rats (NU group) and
      compared with those of a control group undergoing ureterolysis, as well as with
      two groups in which the ureter was used as an autologous free graft (in one of
      these groups the ureter was integrated into the urinary tract by anastomosis,
      whereas in the other group the ureter was not integrated). The main
      histomorphometrical parameters were thickness or length and surface or area.
      Thickness measurements were made using a micrometer. For area determinations,
      paper prints of light micrographs from each segment were measured using a Koizumi
      KP-90 digital planimeter. A non-parametric variance analysis (Kruskal-Wallis
      test) was used to compare the results. These results were compared with those of
      the Wilcoxon test. The results are expressed as different levels of alpha, (0.05,
      0.01 and 0.001). RESULTS: When p < 0.01, there were practically no statistically
      different variables between NU and AU. Comparison of NU to SC and SC to AU showed
      only seven statistically different variables. Muscle layer thickness was
      different only when the comparison was made with the RUb group. When p < 0.001,
      RUa and RUb were not different, nor were NU and AU or SC and NU. Differences were
      observed between RUb and all the other groups. RUa was different from NU, SC, or
      AU in 3, 4 or 5 of the 18 variables analyzed. Most of the surface variables were
      significantly different in RUb in comparison to the other groups. There were also
      differences between RUa and NU, as well as between NU and SC, in the area of the
      lamina propria. CONCLUSIONS: Initial ischemia and denervation are not the cause
      of the observed changes, as these changes are different in both types of free
      graft. Histomorphometrical studies constitute a useful method in the assessment
      of differences between ureteral free graft groups. None of the histomorphometric
      findings is inconsistent with the use of the rat ureter as a free graft.

PMID- 8988654
TI  - Comparison between results of ileal conduit and continent ileal bladder (VIP),
      after radical cystectomy.
AB  - OBJECTIVES: The aim of the present study is to analyze the results achieved with
      the ileal bladder according to the VIP (vescica ileale Padovana) procedure.
      METHODS/RESULTS: We compared the results obtained in 31 patients with invasive
      bladder cancer who underwent radical surgery (22 underwent the ileal conduit
      procedure and 9 were treated by orthotopic bladder substitution) and analyzed the
      early complications, long-term results and physiological data of the group
      submitted to the VIP procedure. In the patient group submitted to the VIP
      procedure, there was only one case who required removal of the new bladder due to
      an enteroneovesical fistula. Another case developed medium serrate anular
      stricture of the bulbar urethra about 8 months postoperatively and was treated by
      endoscopic urethrotomy. The uroradiologic and urodynamic evaluations confirmed
      urinary tract stability integrity of renal function and good adaptation of the
      new reservoir. The andrological studies showed complete sexual potency in 2 of 9
      patients. CONCLUSIONS: The VIP procedure appears to be a good technique, with
      complications no greater than those of traditional urinary diversion, and
      improves the quality of life of patients undergoing radical surgery for invasive
      bladder cancer.

PMID- 8988655
TI  - Atypical metastasis from prostatic carcinoma. Report of a case of renal
      metastasis and literature review.
AB  - Occult prostatic carcinoma (carcinoma diagnosed because of the presence of
      metastasis) is commoner and commoner; the sites for metastatic disease are
      progressively more diverse. This is partially due to the longer life of the
      general population and to the better expectative of life for oncologic patients
      with modern treatments. We report the first case to our knowledge, of occult
      prostatic carcinoma diagnosed in a patient with a parenchymatous acute renal
      failure secondary to diffuse metastatic infiltration. We also review other
      atypical locations of metastasis from prostatic carcinoma reported in the
      literature and discuss the ways of spread in these cases.

PMID- 8988656
TI  - Subchorionic placental cyst: histopathological and clinical aspects in two cases.
AB  - Authors report here two cases of subchorionic placental cysts with diameters of 5
      x 6 cm and 10 x 12 cm, respectively, diagnosed by ultrasound in pregnancy.
      Subsequent histological and biochemical examinations seem to prove their origin
      from the trophoblastic "X-cells" and confirm their frequent benign nature.

PMID- 8988657
TI  - Fibroadenoma of the vulva. Report of a case.
AB  - A case of fibroadenoma occurring in the vulva of a 24 year old woman is
      presented. This rare benign tumor appears as dermal or subcutaneous well
      circumscribed nodule. Histologically the fibroadenoma is characterized by
      epithelial and stromal proliferation. Two different concepts concerning
      histogenesis are cited; the authors believe that this tumor arises in ectopic
      mammary tissue.

PMID- 8988658
TI  - Aortoesophageal fistula. Report of one case complicating foreing body ingestion
      with considerations about pathogenesis.
AB  - Aorto-esophageal fistula is a very rare disease and few cases are reported. The
      most frequent ethiological factors are foreign body ingestion primary disease of
      esophagus or aorta and iatrogenic damages in particular endoscopical
      investigations. In this report a new case is described and a pathogenic
      explanation for the development of the disease is proposed.

PMID- 8988659
TI  - Some considerations about the "Fibrolipocalcareous myopathy" (Mattioli-Foggia and
      Raso disease).
AB  - Fibrolipocalcareous myopathy also known as Mattioli-Foggia and Raso Disease was
      observed first time in 1945. They described clinical, anatomopathologic and
      radiological Bigliardi aspects. At present the published cases are more than
      forty. We have pointed out our attention on the published cases. We believe,
      regard to histopathological and whole clinical data, that this disease could be
      considered as a) the outcome of a vascular hamartoma; or b) the consequence of a
      "mesoblastic phacomatosis".

PMID- 8988660
TI  - Primary solitary meningioma of the lung.
AB  - Light microscopic, ultrastructural and immunohistochemical features of a case of
      primary meningioma of the lung are described in this report. The lesion was
      incidentally discovered in the right lung of a 68-year-old man and treated by
      lobe resection. No evidence of recurrence or metastasis has been detected 2 years
      after surgery. The literature is reviewed and the differential diagnosis from
      other neoplasms presenting as coin lesions in the lung is stressed. Different
      histogenetical theories and the relation to so-called "minute pulmonary
      chemodectomas" are discussed.

PMID- 8988661
TI  - Barber poles, battlefields, and wounds that will not heal.

PMID- 8988662
TI  - Hayes Martin Lecture. The physician (ARZT) and the arts.

PMID- 8988663
TI  - Repair of midline vertical lower lip deficiency after mandible reconstruction.
AB  - BACKGROUND: When lower lip incisions are combined with anterior oromandibular
      resection and composite flap reconstruction, increased potential exists for
      abnormal healing of the lower lip. The aim of this study is to describe these
      deformities and operative techniques for their correction. METHODS: A
      retrospective review of all patients undergoing oromandibular reconstruction with
      osteocutaneous free tissue transfer at Indiana University Medical Center and
      Affiliated Hospitals during the 5-year period between January 1991 and 1996 was
      performed. Patients requiring secondary lower lip revision or repair were
      identified. Patient characteristics, lip deformities, and operative correction
      techniques were detailed. RESULTS: Sixty patients underwent 62 free tissue
      transfers for oromandibular reconstructions. Five patients (7.1%) required
      reoperation for lower lip deformities related to abnormal wound healing. All
      affected patients had lower lip split incisions for access to the oropharynx and
      composite anterior floor of mouth and mandibular resection and reconstruction.
      Each patient had successful repair of the lower lip deformity and correction of
      related functional deficits using lower lip tissue. CONCLUSION: Lower lip
      deformities occur in a subset of patients undergoing anterior mandibular
      reconstruction. Horizontally redundant lower lip tissue can be mobilized to
      repair the secondary aesthetic and functional deficits.

PMID- 8988664
TI  - Validation and clinical application of computer-combined computed tomography and
      positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose head and neck
      images.
AB  - BACKGROUND: Positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose
      (PET-FDG) improves the detection of head and neck squamous cell cancer (HNSCC),
      but lacks anatomical detail. The accuracy of registered computed
      tomography/magnetic resonance (CT/MR) and PET-FDG in delineation of HNSCC at the
      primary site and its clinical application was investigated. METHOD:
      Preoperatively 30 patients were staged clinically and each had either CT (23), MR
      (5), or both CT and MR (2) scans, as well as CT/MR-PET-FDG registration. Tumor
      margins or infiltration of specific anatomical landmarks on the different scans
      were compared and judged against histology. RESULTS: For primary tumors CT-PET
      FDG (97%) and MR-PET-FDG (100%) delineated the tumor more accurately than CT
      (69%) or MR (40%) alone. Similarly, CT-PET-FDG (98%) and MR-PET-FDG (100%) were
      better than CT (70%) and MR alone (80%) in identifying tumor invasion of specific
      anatomical structures. Management was altered in 7 of 30 patients. The registered
      images were particularly useful in delineating tumor extension in the
      infratemporal fossa, maxilla and mandible, and identifying recurrences obscured
      by scar tissue. CONCLUSIONS: It is possible to accurately register CT, MR, and
      PET-FDG data sets in the head and neck. The initial results show that registered
      CT/ MR-PET-FDG images provide additional clinically relevant information over
      that obtained from clinical evaluation or conventional CT/MR imaging.

PMID- 8988665
TI  - Evaluation of single isotope technetium 99M-sestamibi in localization efficiency
      for hyperparathyroidism.
AB  - BACKGROUND: Regardless of surgical effectiveness, ongoing activity in parathyroid
      localization in hyperparathyroidism (HPT) is an established enterprise. Sestamibi
      (MIBI), the most recent new modality, is being assessed in this regard. METHODS:
      Twenty mCI of 99 TC Sestamibi was administered intravenously in patients with
      prospective HPT. Images were assessed by pinhole and full-field gamma camera at
      20 minutes and 2 hours. Dual-phase one isotope only was utilized. Patients were
      then studied for pathology and MIBI correlation. RESULTS: Sixty-three cases
      underwent MIBI scanning, 50, or 79%, of which were due to a single adenoma.
      Sensitivity showed in 41 of 50 adenomas and was 82% correct. Quadrant
      localization was 97%. Eleven patients showed hyperplasia with MIBI sensitivity of
      82% on a case basis but only 31% for multiglandular disease. Overall MIBI
      sensitivity is 80%. One false-positive and one true-negative case were observed.
      All patients achieved eucalcemia. No operative morbidity of significance
      occurred. CONCLUSION: Scanning with 99M Sestamibi dual-phase technique is the
      preferred mode of parathyroid localization in current practice. It is of
      assistance in primary HPT, essential in recurrent HPT, and of use in ectopic
      gland detection. It can support surgical intervention in the marginal HPT
      patient. Scanning still requires bilateral exploration for complete assessment.

PMID- 8988666
TI  - Preoperative parathyroid localization with sestamibi.
AB  - PURPOSE: Results of noninvasive preoperative parathyroid localization with
      technetium99m-labeled sestamibi are reported in a series of 51 patients. PATIENTS
      AND METHODS: Forty-four patients had hyperparathyroidism surgically treated for
      the first time and seven patients underwent reexploration for recurrent or
      persistent hyperparathyroidism. Preoperative scintigraphy with sestamibi was
      performed in all patients before surgical exploration. Results of the
      radionuclide studies were compared with surgical and pathologic findings.
      RESULTS: Twenty-six patients had solitary adenomas. All 26 were localized
      preoperatively by the scans. Among 18 patients with multiglandular pathology, 69
      pathological glands were found at surgery. Thirty-six of these glands, in 15
      patients, were localized by the scans. Among the 7 patients evaluated after
      failed exploration or recurrent hyperparathyroidism, 7 pathologic glands were
      found, of which 6 were correctly localized by the scan. Ectopic lesions in 2
      patients were correctly localized by the scan. CONCLUSIONS: The authors conclude
      that sestamibi parathyroid localization is an effective method for preoperative
      parathyroid localization, with accuracy exceeding that of other noninvasive
      studies.

PMID- 8988667
TI  - Decreased expression of transforming growth factor beta receptors on head and
      neck squamous cell carcinoma tumor cells.
AB  - BACKGROUND: Transforming growth factor beta (TGF-beta) has antiproliferative
      effects on normal and neoplastic cells that express specific TGF-beta receptors.
      We hypothesize that diminished expression of TGF-beta and/or its receptors may
      contribute to the uncontrolled proliferation of head and neck squamous cell
      carcinoma (HNSCCA) cancer cells. METHODS: Using immunohistochemical techniques,
      we characterized the expression of TGF-beta isoforms and TGF-beta receptors, TGF
      beta(RI) and TGF-beta(RII), in HNSCCA. Tumor production of TGF-beta was evaluated
      in culture supernatants from a cytokine-stimulated HNSCCA tumor line (HTB-43).
      RESULTS: All control specimens displayed strong cell-associated staining of TGF
      beta as well as both receptors. Forty-seven of 47 cancer specimens exhibited
      positive staining for TGF-beta in the tumor matrix. Forty of the 47 cancer
      specimens demonstrated no expression of TGF-beta(RI), and 43 of the 47 expressed
      no TGF-beta(RII). Only interleukin 1 alpha (IL-1 alpha) and IL-1 beta induced
      significant TGF-beta expression from the HTB-43 cells. CONCLUSIONS: Decreased
      expression of TGF-beta receptors may play a significant role in the pathogenesis
      of HNSCCA by allowing uncontrolled cell proliferation.

PMID- 8988668
TI  - Supraspinal accessory lymph node metastases in supraomohyoid neck dissection.
AB  - BACKGROUND: Some patients undergoing surgical resection of primary squamous cell
      carcinoma of the oral cavity and oropharynx also undergo supraomohyoid neck
      dissection for staging of the negative (N(o)) neck. Dissection of the supraspinal
      accessory lymph node pad requires significant traction of the spinal accessory
      nerve. There are currently no data to indicate the incidence of metastases to
      this site and thus the necessity of performing dissection of these nodes.
      METHODS: A prospective analysis of a consecutive series of 44 patients with newly
      diagnosed squamous carcinoma of the oral cavity or oropharynx undergoing surgical
      management of the primary lesion with staging neck dissection was performed.
      Patients underwent unilateral (41) or bilateral (3) supraomohyoid neck dissection
      with separate submission of the supraspinal accessory lymph node pad for
      pathologic evaluation to determine the incidence of nodal metastases. RESULTS: A
      total of 15 patients (32%) had microscopic metastatic squamous cell carcinoma
      involving the supraomohyoid neck dissection specimen. Only 1 patient had a
      metastatic deposit involving the supraspinal accessory lymph node pad. This
      patient also had metastases in additional lymph nodes at level II. There was an
      equal incidence of metastases for all patients when stratifying by T stage.
      CONCLUSION: This preliminary report reveals a small incidence of supraspinal
      accessory lymph node metastases in patients with T + NO squamous cell carcinoma
      of the oral cavity and oropharynx. We continue to accrue patients to determine if
      the incidence of supraspinal accessory lymph node metastases varies with an
      increased number of patients.

PMID- 8988669
TI  - Supraomohyoid neck dissection.
AB  - BACKGROUND: Supraomohyoid neck dissection (SOHND) has assumed increasing
      importance as a staging lymphadenectomy in patients with N(o) oral and
      oropharyngeal squamous cell carcinoma (SCC), as well as a potentially curative
      procedure in selected patients with limited metastatic disease in the neck.
      METHODS: Retrospective chart review of 287 patients who had a total of 320 SOHND
      for SCC between 1986 and 1993 as a follow-up to an earlier report that covered
      our experience between 1980 and 1985. After excluding 24 patients who also had
      local recurrence, or a new primary, the remaining 296 SOHND were assessed for the
      effectiveness of tumor control in the neck. RESULTS: Of 248 elective SOHND,
      clinically negative nodes proved histologically positive in 60 patients (25%),
      only 4 of whom failed in the neck (7%). A total of 48 patients (16%) had a
      therapeutic SOHND for limited N+ disease, confirmed pathologically in 31, with
      neck recurrence documented in 2 (6%). Nodes proved negative histologically in 205
      patients, 10 of whom failed in the neck (5%). Nine of the 16 patients with neck
      recurrence had received postoperative radiation therapy and 9 recurred within the
      field of the SOHND. CONCLUSIONS: SOHND is a reliable staging procedure in
      patients with N(o) oral or oropharyngeal SCC. Therapeutic SOHND, in conjunction
      with postoperative radiation therapy, was highly effective in controlling neck
      metastases in carefully selected patients with limited disease in the upper neck.

PMID- 8988670
TI  - Selective neck dissection and the management of the node-positive neck.
AB  - OBJECTIVE: To assess the oncologic effectiveness of the selective neck dissection
      (SND) in patients with both clinically and pathologically proven regional
      metastases. METHODS: A 4-year retrospective medical chart review was conducted in
      an academic tertiary care referral center. Twenty-nine patients with a newly
      diagnosed upper aerodigestive tract squamous cell carcinoma, and both clinically
      and histologically proven cervical metastases who underwent 36 SND, had their
      records reviewed. Minimum follow-up was 2 years. RESULTS: Regional metastasis
      were staged N1 in 13 patients, N2A in 1, N2B in 8, and N2C in 7. Seventeen
      supraomohyoid and 19 lateral neck dissections were performed. Extracapsular
      spread of tumor was present in 11 patients. Postoperative radiation therapy was
      administered to 20 patients. Actuarial disease-specific survival at 4 years was
      47% overall, 67% in N1 patients, and 41% in N2 patients. Only 1 failure in the
      treated neck occurred for a 4-year actuarial regional failure rate of 4%. The
      actuarial local failure and distant metastasis rate were 36% each. CONCLUSIONS:
      In carefully selected patients with clinically and histologically apparent
      regional metastases, the selective neck dissection can be an oncologically
      effective procedure.

PMID- 8988671
TI  - The utility of routine frozen section examination for intraoperative diagnosis of
      thyroid cancer.
AB  - BACKGROUND: The value of routine frozen section examination for intraoperative
      diagnosis of thyroid cancer and determination of extent of thyroidectomy is
      controversial and needs to be evaluated on an institution to institution basis.
      METHODS: A prospective evaluation of 76 patients with nodular thyroid disease who
      had an adequate fine needle aspiration biopsy (FNAB) underwent thyroidectomy with
      routine thyroid frozen section examination. A direct comparison of FNAB and
      frozen section examination, along with a cost benefit analysis of frozen section
      examination, was completed. RESULTS: The thyroid pathology was carcinoma in 24,
      follicular adenoma in 24, multinodular goiter in 24, thyroiditis in 3, and a cyst
      in 1 patient. The sensitivity, specificity, and accuracy of frozen section
      examination were 93%, 100%, and 97%, respectively, compared with 88%, 89%, and
      91% for FNAB (P > 0.05). Diagnosis was deferred in 38 patients (50%) in whom
      frozen section examination showed a follicular neoplasm. One to 6 frozen section
      examinations were obtained per patient with alteration in intraoperative
      management in only 2 patients (3%) at a charge of $246 to $606 per patient and a
      total charge of $26,040. CONCLUSION: In patients with an adequate FNAB, frozen
      section examination rarely affected intraoperative decision making in thyroid
      surgery and its routine use was not cost effective.

PMID- 8988672
TI  - Conservation surgery for recurrent carcinoma of the glottic larynx.
AB  - BACKGROUND: Partial laryngectomy following previous irradiation is an
      oncologically sound procedure with excellent local control and survival rates.
      Several reports suggest an increased complication rate in previously irradiated
      patients. METHODS: To analyze whether previous irradiation affected
      complications, disease control, or survival we performed a retrospective analysis
      of all patients who underwent vertical partial laryngectomy (VPL) for squamous
      cell carcinoma of the glottic larynx between January 1984 and August 1993.
      RESULTS: Sixty-eight patients had adequate followup. The overall 5-year survival
      rates were 79% for previously treated patients and 95% for primary VPL patients
      (P = NS). The local control rates with surgical salvage were 93% and 98%,
      respectively. No increase in wound complications, time to decannulation, length
      of hospitalization, or ability to swallow were found. CONCLUSIONS: VPL can be
      performed safely in selected patients following previous radiotherapy without a
      significant increase in complications or cost.

PMID- 8988673
TI  - A retrospective comparison of treatment outcome in the posterior and anterior
      tongue.
AB  - BACKGROUND: The perceived poor survival for tongue base cancer compared with the
      anterior tongue influences selection of treatment. METHODS: Treatment outcome is
      compared in patients with epidermoid carcinoma of the tongue base (n = 112) and
      anterior tongue (n = 188). A multivariate Cox's proportional hazard model is used
      to assess the independent effect of tumor location on survival. RESULTS: Seventy
      one percent of patients with tongue base tumors had advanced stages of disease
      (Stages III & IV) at presentation compared with 32% for the anterior tongue (P =
      .000). Disease-specific survival at 5 years for the tongue base was 26%, and for
      the anterior tongue was 64%. Significant risk factors for disease relapse
      included age > 50 years, advanced stages of disease, and radiotherapy as a single
      treatment modality. The adjusted hazard ratio for disease relapse for the tongue
      base compared with the oral tongue was 1.2 (95% CI = 0.83, 1.74; P = .332).
      CONCLUSIONS: Treatment response for tongue base and anterior tongue tumors is
      similar. The pessimism that besets the management of cancer of the tongue base
      may not be justified in all patients.

PMID- 8988674
TI  - Glutathione S-transferase and cytochrome-P-450 polymorphism as risk factors for
      squamous cell carcinoma of the larynx.
AB  - PURPOSE: While cigarette smoking and alcohol consumption are recognized
      covariates for laryngeal carcinoma, the role of genetic factors in determining
      individual susceptibility is unknown. We describe the influence of polymorphism
      in carcinogen-metabolizing enzymes on susceptibility to squamous cell carcinoma
      of the larynx. MATERIAL AND METHODS: We investigated 269 patients with T1-T4
      laryngeal carcinoma and 216 controls. Enzyme genotypes at the glutathione-S
      transferase GSTM1 (A, B, A/B, null), GSTM3 (A, B), GSTT1 (null and expressors),
      and cytochrome P-450, CYP2D6 (intron 3/exon 4 boundary mutation and exon 5
      deletion), CYP1A1 (3'-mutation and exon 7 mutation), and CYP2E1 (mutation at the
      5' flanking region) loci were determined using polymerase chain reaction and
      restriction-based approaches. RESULTS: While the frequencies of the heterozygote
      GSTM1 A/B and homocygote GSTM3 B/ B were statistically significantly lower in
      cases than controls, the frequency of the GSTT1 null genotype was higher in the
      cases than controls. Genotype frequencies of 123 patients suffering squamous cell
      carcinomas located at different sites within the upper aerodigestive tract showed
      no differences between cases and controls. CONCLUSIONS: The data provide evidence
      that susceptibility to laryngeal carcinoma, but not pharyngeal carcinoma, is
      mediated by allelism at a number of loci encoding enzymes involved in the
      detoxification of electrophils derived from environmental pollution including
      cigarette smoke.

PMID- 8988676
TI  - A modified method of carcinogenesis induction in the DMBA hamster cheek pouch
      model of squamous neoplasia.
AB  - BACKGROUND: The classic hamster cheek pouch model of squamous cell neoplasia
      requires triweekly application of 9,10-dimethyl-1,2-benzanthracene (DMBA) on
      tissues for 20 weeks. This study describes a new methodology for induction of
      neoplasia using a sustained-release delivery of carcinogen that is less labor
      intensive with decreased risk to personnel. METHODS: Cotton sutures were
      impregnated with DMBA and coated with silicone elastomer. These sutures were then
      placed in the cheek pouch of animals, were harvested at weekly intervals, and
      residual DMBA was measured confirming sustained release. Carcinogenesis was
      compared in Syrian hamsters grouped into classic triweekly painted model (n =
      10), sustained-release DMBA (n = 19), sustained-release with weekly painting (n =
      17), and control (n = 10). RESULTS: The sustained-release implants resulted in a
      90% yield of squamous neoplasia at 20 weeks, similar to the classic painted model
      but with less handling of the carcinogen and the animals. CONCLUSIONS: This model
      is safer for personnel, time efficient, and effective for inducing
      carcinogenesis.

PMID- 8988675
TI  - Fluorescence imaging and spectroscopy of 5-aminolevulinic acid induced
      protoporphyrin IX for the detection of neoplastic lesions in the oral cavity.
AB  - BACKGROUND: Semiquantitative fluorescence measurements following topical
      application of 5-aminolevulinic acid (5-ALA) in 16 patients with neoplastic
      lesions of the oral cavity were performed. METHODS: Time course and type of
      porphyrin accumulation were analyzed in neoplastic and surrounding healthy tissue
      by measuring emission spectra of 5-ALA-induced protoporphyrin IX fluorescence.
      Fluorescence images in the red and green spectral range from the tumor tissue
      were recorded with a charge-coupled device camera. RESULTS: Protoporphyrin IX
      fluorescence was detected in the oral mucosa of all patients after local
      application of 5-ALA. Protoporphyrin IX in neoplastic tissue accumulated earlier
      in comparison with the surrounding normal tissue. The maximum fluorescence
      contrast of 10:1 between tumor and host tissue was generally seen 1-2 hours after
      application, allowing a demarcation of tumor tissue even with the naked eye.
      CONCLUSION: Labeling of mucosal lesions of the oral cavity with Protoporphyrin IX
      fluorescence induced by the local application of 5-ALA seems to be a promising
      diagnostic procedure for neoplastic lesions that are difficult to visualize under
      white light examination. It is the aim of further investigations to evaluate the
      relevance of this new diagnostic procedure as a noninvasive and sensitive method
      for patients with oral cancer.

PMID- 8988677
TI  - The erbB oncogenes as prognostic markers in oral squamous cell carcinomas.
AB  - BACKGROUND: In clinical practice it became clear that conventional prognostic
      parameters of oral squamous cell carcinomas (OSCC) are of limited value for the
      prediction of a disease-free survival. The overexpression of erbB oncogenes is of
      importance for the clinical course of a variety of solid tumors. After
      discovering amplifications of erbB oncogenes even in OSCC, it was the aim of the
      present study to clarify the potential of oncogenes as additional prognostic
      markers. MATERIALS AND METHODS: The amplification of the erbB oncogenes in
      tumorous tissue of 85 OSCC patients was determined using the double-differential
      polymerase chain reaction. Histologically healthy mucosa in these patients was
      also studied. In univariate analysis the amplification of erbB oncogenes with
      clinical and histopathological prognostic parameters was compared. RESULTS: No
      significant correlation between common prognostic parameters and erbB-2
      amplification was found. Patients whose OSCC tissue showed an average gene copy
      number for erbB-2 of greater than 1.2, for erbB-3 below 0.11, and a ratio of erbB
      1 and erbB-2 below 0.31 had a statistically significant decrease in disease-free
      survival. Even in histologically healthy oral mucosa from tumor patients an
      amplification of erbB oncogenes was found. CONCLUSIONS: ErbB oncogene
      amplifications in oral squamous cell carcinomas play a significant role as a
      prognostic factor and seem to be effective in predicting decrease in disease-free
      survival. Genetic abnormalities in tumor-surrounding tissue support the field
      cancerization hypothesis.

PMID- 8988678
TI  - Argyrophilic nucleolar organizer regions staining is useful in predicting
      recurrence-free interval in oral tongue and floor of mouth squamous cell
      carcinoma.
AB  - BACKGROUND: Argyrophilic nucleolar organizer regions (AgNORs) represent a tissue
      marker of cell proliferative activity. The purpose of this study was to assess
      the prognostic value of AgNORs expression in oral squamous cell carcinoma (SCC).
      METHODS: The AgNORs area/nucleus was studied in paraffin sections by means of
      digital image analysis in 43 cases of stage II oral tongue and floor of the mouth
      SCC. RESULTS: Time free of disease was considered a dependent variable of a
      binary indicator of AgNORs expression (7.77 microns2/nucleus as a cut-off point).
      High AgNORs level was associated with a statistically significant negative effect
      on recurrence-free interval of disease in a Cox proportional hazards models
      controlled for occult lymph node metastasis, involvement of the surgical margins,
      thickness of the lesion, and vascular invasion. CONCLUSIONS: The AgNORs area
      increased the capability of predicting which patients have a high risk of
      recurrence of cancer, and its evaluation may provide useful information for the
      therapeutic approach to the oral tongue and floor of the mouth SCC.

PMID- 8988679
TI  - The extent of neck disease after regional failure during observation of the N0
      neck.
AB  - BACKGROUND: The optimum management of the N0 neck remains controversial. When the
      neck is observed it is hoped that close follow-up will detect regional failure at
      an early stage. To test this hypothesis we examined patients undergoing
      therapeutic neck dissection for newly developed neck metastases during
      observation after treatment of the primary tumor. METHODS: A retrospective chart
      review of 47 patients undergoing neck dissection for regional failure after
      surgical treatment of the primary tumor and observation of the neck from 1987 to
      1992 was performed. The median time to failure in the neck was 13 months.
      RESULTS: The clinical neck stage at the time of neck dissection was N1 in 37, N2A
      in 6, N2B in 1, and N3 in 3. However, pathologic staging revealed stages of N1 in
      19, N2A in 5, N2B in 20, and N3 in 3. Extracapsular spread (ECS) was present in
      23 patients (49%). Overall 36 patients (77%) had adverse pathologic findings (N
      greater than 1 or ECS). CONCLUSIONS: These data indicate that when observation is
      used for the neck at risk for metastasis, patients tend to fail with high stage
      disease in the neck. This supports the philosophy of elective treatment of the
      neck but cannot show whether elective treatment will improve survival.

PMID- 8988680
TI  - Patterns of nodal and distant metastasis based on histologic varieties in
      differentiated carcinoma of the thyroid.
AB  - BACKGROUND: Understanding of differentiated carcinoma of the thyroid has improved
      in recent years with the definition of prognostic factors and risk group
      analysis. We intend to review our experience of differentiated thyroid cancer in
      relation to the risk of nodal and distant metastasis based on various histologic
      subgroups. METHODS: This is a retrospective review of a consecutive series of
      1,038 previously untreated patients with differentiated carcinoma of the thyroid
      treated over a period of 55 years. Univariate and multivariate analysis of
      various prognostic factors was performed. The incidence of nodal and distant
      metastasis was analyzed based on various histologic varieties of differentiated
      thyroid cancer. RESULTS: There were 337 male and 701 female patients. The various
      histologic subgroups included papillary (810), follicular (169), and Hurthle cell
      cancer (59). The cumulative risk of nodal metastasis based on histological group
      was 61%, 30%, and 21% for papillary, follicular, and Hurthle cell variety,
      respectively. The risk of distant metastasis for the same histologic varieties
      was 10%, 22%, and 33%, respectively. The 5- and 20-year survival for these
      histologic subgroups was papillary (94% and 87%, respectively), follicular (87%
      and 81%), and Hurthle cell tumors (81% and 65%; P < 0.001). CONCLUSIONS: The
      incidence of nodal metastasis is highest in the papillary subgroup; however, the
      incidence of distant metastasis was 33% in the Hurthle cell variety. The risk of
      nodal and distant metastasis varies considerably based on individual histologic
      variety.

PMID- 8988681
TI  - Management of the neck in parotid carcinoma.
AB  - BACKGROUND: Management of the clinically negative neck remains a controversial
      issue in patients with carcinoma of the parotid gland. Our treatment policy has
      always been conservative, reserving lymphadenectomy for selected patients.
      METHODS: We retrospectively evaluated 121 patients with malignant tumors of the
      parotid gland who received their definitive treatment at the Memorial Sloan
      Kettering Cancer Center between 1966 and 1988. RESULTS: A total of 35 neck
      dissections (ND) were performed, 14 of which involved removal of clinically
      positive nodes (radical in 10, modified in 2, and limited in 3). Twenty-one
      patients had an elective lymphadenectomy (radical in 14, modified in 2, and
      limited in 4), usually because of ominous histology or high T stage. In addition
      to histologically positive regional lymph nodes, facial nerve paralysis, gender,
      and advanced stage, the decision to perform a ND, whether elective or
      therapeutic, was significantly predictive of decreased survival (P < 0.001). In
      the majority of patients (86, or 65%), the neck was observed rather than treated
      electively, with no impact on overall survival. Only 4 of 121 patients developed
      neck recurrence following treatment, including 3 who had neck dissection as part
      of their initial management. CONCLUSIONS: These data support our policy of
      reserving elective ND only for those histologic diagnoses that carry the highest
      risk of nodal metastases, as well as for selected patients whose primary tumor
      resection might be facilitated by lymphadenectomy.

PMID- 8988682
TI  - Parathyroid surgery using monitored anesthesia care as an alternative to general
      anesthesia.
AB  - BACKGROUND: Although there have been several reports in the literature describing
      a renewed interest in performing thyroid surgery under local anesthesia (LA),
      there has been little information regarding parathyroid surgery under local
      anesthesia. METHODS: We retrospectively reviewed our experience of 49 LA
      parathyroid patients over a 9-year period at a single institution. A bilateral
      cervical block (C2-C3) was administered by a single surgeon using lidocaine and
      bupivacaine. RESULTS: The study included 39 females and 10 males with an average
      age of 62 years (range, 35-89 years). Every surgery was curative and the final
      pathology revealed 46 parathyroid adenomas and 3 cases of parathyroid
      hyperplasia. Forty-seven percent of the patients were discharged within 6 hours
      of operation and the remaining patients had a 1.4-day average length of hospital
      stay. A group of age- and sex-matched controls who underwent parathyroid surgery
      using general anesthesia (GA) served as a control group with 27% of operations
      performed as outpatients and an average length of stay of 1.6 days. Return to
      work averaged 6 days for the LA group versus 8 days for the GA. In the LA group,
      there was one instance of postoperative hemorrhage requiring reoperation and one
      instance of conversion to GA secondary to an inability to tolerate LA. There were
      no instances of recurrent laryngeal nerve injury or permanent hypoparathyroidism
      in either group. CONCLUSIONS: These data suggest that experienced surgeons can
      perform parathyroid surgery safely and effectively using LA as an alternative to
      GA.

PMID- 8988683
TI  - The value of computed tomography scan versus an explorative surgical approach for
      removal of squamous cell carcinoma of the posterior pharyngeal wall.
AB  - BACKGROUND: The prevertebral fascia plays a key role in surgery of posterior
      pharyngeal wall tumors. Invasion of the prevertebral muscles determines the
      irresectability of the tumor and accurate diagnosis of invasion posteriorly is a
      prerequisite for major ablative surgery. METHODS: A retrospective study was
      performed to define the value of CT scanning versus open neck exploration with
      regard to the resectability of posterior pharyngeal wall carcinoma. The
      predictive value of preoperative CT scans was assessed and compared with the
      outcome of open neck exploration and resectability of the primary tumor, using
      the final histopathology report as a gold standard. RESULTS: Nineteen patients
      with 20 tumors were included in this study. Overall the CT scan was correct
      concerning prevertebral muscle status in 4 out of 20 (20%), whereas open neck
      exploration was correct in 18 tumors (90%). CONCLUSION: The predictive value of a
      suspicious CT scan in determining prevertebral muscle invasion is extremely low
      in this study. Open neck exploration seems to be superior for determining
      resectability of posterior wall carcinoma.

PMID- 8988684
TI  - Phonomicrosurgical treatment of early glottic cancer and carcinoma in situ.
AB  - BACKGROUND: In recent years, transoral resection of early glottic cancer has
      developed into a phonomicrosurgical approach that resulted from the convergence
      of microlaryngoscopic surgical technique theory with body cover mucosal wave
      theory of voice production. The vocal outcome from these procedures has improved
      by minimizing the deep resection margin and thereby maximizing the preservation
      of the vocal folds' normal layered microstructure (laminae propria and
      epithelium). Recurrence and cure rates from this narrow-margin approach were
      examined. METHODS: The phonomicrosurgical resection approach is composed of four
      basic procedures in which there is an increasing depth of resection to
      accommodate a narrow-field deep cancer margin. This approach was employed to
      treat 13 T1 cancers and 7 with carcinoma in situ (CIS). RESULTS: No patients who
      underwent a cancer resection developed a recurrence. Minimum follow-up on these
      patients was 2 years and the mean follow-up was 42 months. In the group with CIS,
      2 patients developed microinvasive carcinoma despite en bloc excision of the CIS.
      Both were successfully treated; 1 was resected transorally and the other
      underwent radiation therapy. CONCLUSIONS: This study indicates that the
      phonomicrosurgical approach, which incorporates a narrow deep cancer margin to
      enhance the postoperative vocal outcome, resulted in standard control and cure of
      early glottic neoplasia.

PMID- 8988685
TI  - An analysis of the treatment of 114 patients with recurrent pleomorphic adenomas
      of the parotid gland.
AB  - BACKGROUND: Nerve preserving surgery is widely recommended for recurrent parotid
      pleomorphic adenomas though the risk of further relapse may be high. Adjuvant
      radiotherapy may improve control but its exact role requires clarification.
      METHODS: A series of 114 patients with first recurrences treated between 1952 and
      1992 is reviewed. Treatment modality was either surgery alone (SG; n = 63) or
      surgery with radiotherapy (SG + RT; n = 51). Results were determined with respect
      to long-term tumor control (K-M life-tables) and facial nerve function. RESULTS:
      The rate to second recurrence was 15% (17/114), median follow-up 14 years. There
      were no cases of malignant degeneration. Multinodular recurrences treated by SG
      were at particular high risk of relapse, but control was significantly improved
      with adjuvant radiotherapy (SG versus SG = RT; 43% versus 4% at 15 years, P =
      0.008). In contrast, no difference was demonstrated in the uninodular tumor group
      (SG versus SG = RT; 15% versus 13% at 15 years, P = 0.9). The incidence of
      permanent facial nerve injury was 15%. CONCLUSIONS: This study emphasizes the
      distinction between multinodular and uninodular recurrences; the former is at
      high risk of relapse and benefits from adjuvant radiotherapy whereas solitary
      tumors may be adequately treated by surgery alone.

PMID- 8988687
TI  - The management of late fetal death: a guide to comprehensive care.

PMID- 8988686
TI  - Hormone replacement therapy in women with liver disease.

PMID- 8988688
TI  - Combining nuchal translucency with umbilical Doppler velocimetry for detecting
      fetal trisomies in the first trimester of pregnancy.
AB  - OBJECTIVE: The aim of our study was to evaluate whether the combined use of
      umbilical artery pulsatility index (UAPI) and nuchal translucency (NT)
      measurements would be useful in the prediction of fetal chromosomal abnormalities
      at 10 to 13 weeks of gestation. DESIGN: A prospective study. POPULATION AND
      METHODS: Five hundred and fifty-three consecutive women with singleton
      pregnancies between 10 and 13 weeks of gestation, who underwent chorionic villus
      sampling at our institution. UAPI and fetal NT thickness were measured
      immediately before the invasive procedure. Pregnancies in which structural
      malformations had been detected by ultrasound were excluded. RESULTS: Using the
      95th centile and 3 mm as the cutoffs for UAPI and NT, respectively, the detection
      rate for all chromosomal anomalies was 84.2%, with a false positive rate (1
      specificity) of 6.6%, a positive predictive value of 31.3%, and a negative
      predictive value of 99.4%. Out of the 553 tested pregnancies 502 had both
      parameters within the normal range and only three of them (0.6%) were
      chromosomally abnormal; in six of the eight cases (75%) in which both parameters
      were abnormal a chromosome anomaly was present. Of the 43 cases in which only one
      parameter was abnormal, 10 were chromosomally abnormal (23.2%). CONCLUSIONS: Our
      results suggest that the presence of chromosomal anomalies may be strongly
      suspected when an increased NT thickness (NT > or = 3 mm) is associated with an
      abnormally high UAPI at 10 to 13 weeks of gestation. The number of cases studied
      is small, however, and these conclusions are tentative and preliminary. The value
      of a single measurement of NT and UAPI for screening purposes needs to be
      substantiated by further investigation.

PMID- 8988689
TI  - Fetal Rhesus D genotyping on amniocytes in alloimmunised pregnancies using
      fluorescence duplex polymerase chain reaction.
AB  - OBJECTIVE: 1. To establish the reliability of fetal amniocyte Rhesus D (RhD)
      genotyping using fluorescence duplex polymerase chain reaction (PCR) and 2. to
      assess the potential clinical impact on management of alloimmunised pregnancies.
      DESIGN: Multicentre observational study. SETTING: Four departments of obstetrics
      and gynaecology in Germany. METHODS: Fourty-four amniotic fluid samples were
      obtained by amniocentesis from a retrospective group of 27 RhD alloimmunised
      pregnancies and 15 samples from 14 women treated prospectively. Two RhD gene
      specific fragments (exon 7 and 10) were amplified using two separate fluorescence
      duplex PCR assays, and laser detected in an automated DNA sequence analyser.
      RESULTS: Amplification of the Rh gene sequences was successful in all samples.
      PCR at the two RhD gene regions resulted in complete concordance. Genotyping
      correctly predicted the RhD status of all fetuses serotyped (n = 41). After
      intrauterine transfusions, PCR identified the RhD type of two fetuses more
      accurately than serotyping. Earlier knowledge of a negative RhD status would have
      rendered unnecessary 12 amniocenteses in four fetuses of the retrospective study
      group, and prevented further invasive testing in one fetus treated prospectively.
      In the latter group, women with a positive fetal RhD genotype underwent intensive
      prenatal care including serial invasive monitoring and intrauterine treatment.
      CONCLUSIONS: Fetal RhD genotyping of amniocytes is a reliable technique with the
      potential to improve routine management of alloimmunised pregnant women.

PMID- 8988690
TI  - Maternal and fetal levels of methionine and homocysteine in early human
      pregnancy.
AB  - OBJECTIVE: To investigate methionine metabolism during normal human embryonic
      development by measuring levels of methionine and total homocysteine in samples
      of maternal serum, extra-embryonic coelomic fluid, and amniotic fluid. DESIGN:
      Cross-sectional observational study. SETTING: Collaboration between St
      Bartholomew's Hospital, London, and the University Hospital of Nijmegen in The
      Netherlands. PARTICIPANTS: Twenty-three women with uncomplicated pregnancies
      between 8 and 12 weeks of gestation before surgical termination of an
      ultrasonographically normal fetus. METHODS: Maternal serum samples were collected
      prior to surgery. Samples of extra-embryonic fluid and amniotic fluids were
      obtained by transvaginal ultrasound-guided coelocentesis and amniocentesis.
      Methionine was measured using an amino acid analyser and total homocysteine by
      high performance liquid chromatography. RESULTS: Levels of methionine were four
      times higher in extra-embryonic coelomic fluid and twice as high in amniotic
      fluid compared with maternal serum. In contrast, the total homocysteine
      concentrations were much lower in both extra-embryonic coelomic fluid and
      amniotic fluid than in maternal serum. All differences were significant (P < or =
      0.01). CONCLUSIONS: The comparatively high concentrations of methionine in extra
      embryonic coelomic fluid and amniotic fluid, and the concomitant low levels of
      total homocysteine in these fluids, suggest a role for methionine metabolism
      during early human pregnancy.

PMID- 8988691
TI  - The intrapartum CTG prior to neonatal encephalopathy at term: a case-control
      study.
AB  - OBJECTIVE: To compare cardiotocograph (CTG) records during labour in cases of
      neonatal encephalopathy and matched controls. DESIGN: Case-control study.
      SETTING: Metropolitan area of Perth, Western Australia. SUBJECTS: Term deliveries
      complicated by neonatal encephalopathy and controls matched for sex, hospital,
      time of birth, day of week of birth and maternal health insurance. MAIN OUTCOME
      MEASURES: Low fetal heart rate (FHR) variability, FHR accelerations, late
      decelerations, total Kreb's score and FIGO classification of CTG records.
      RESULTS: The neonatal encephalopathy group had significantly more abnormal CTG
      records (89%) classified according to FIGO, although 52% of control CTG records
      were also abnormal. CTG records from cases developed significant differences in
      terms of absence of FHR accelerations and low FHR variability, but not late
      decelerations, prior to delivery. CONCLUSION: Given the low incidence of neonatal
      encephalopathy in this study (7 per 1000) the predictive value of an abnormal CTG
      record is clinically unhelpful. However, the changes in the FHR in such cases
      suggest a greater disturbance of fetal (rest-activity) behaviour during labour.

PMID- 8988692
TI  - Ripening and dilatation of the unfavourable cervix for induction of labour by a
      double balloon device: experience with 250 cases.
AB  - OBJECTIVE: To determine the efficacy of the double balloon device (the Atad
      Ripener Device) in ripening and dilatation of the unfavourable cervix for
      induction of labour. METHODS: Two hundred and fifty women with unfavourable
      cervices (Bishop score < or = 4) underwent induction of labour with the Atad
      Ripener Device. Indications were pregnancy induced hypertension (n = 118), post
      dates (n = 69), elective inductions (n = 23), other reasons including
      nonreassuring nonstress test, intrauterine growth retardation, previous caesarean
      section and diabetes mellitus (n = 40). The Atad Ripener Device was inserted into
      the cervix, the uterine balloon inflated in the internal os, and the cervico
      vaginal balloon in the external os of the cervix (100 mL of normal saline to each
      balloon). Pressure produced by the inflated balloons caused gradual dilatation
      and effacement of the cervix. The Atad Ripener Device was removed 12 h after
      insertion, the cervix assessed again, and labour managed according to obstetrical
      criteria. RESULTS: The Atad Ripener Device caused an increase in the Bishop score
      in all subgroups with a mean change of 4.6 (from 2.0 prior to induction to 6.6
      upon removal of the Atad Ripener Device; P < 0.05). The mean time interval from
      insertion of the Atad Ripener Device to delivery was 18.9 h, and from removal to
      delivery was 6.9 h. Caesarean section was performed in 39/250 patients (16%), and
      the others had a normal vaginal delivery. CONCLUSIONS: 1. The double balloon
      device induces significant ripening and dilatation of the unfavourable cervix. 2.
      Induction of labour was successfully achieved following removal of the Atad
      Ripener Device. 3. Our caesarean section rate was low compared with rates
      reported for women with an unfavourable cervix induced by other methods.

PMID- 8988693
TI  - Stepwise compared with rapid application of vacuum in ventouse extraction
      procedures.
AB  - OBJECTIVE: To compare a one-step (rapid) application of negative pressure
      (vacuum) with conventional stepwise application for ventouse extraction following
      a prolonged second stage of labour. DESIGN: Randomised controlled study. SETTING:
      Teaching Hospital. PARTICIPANTS: Forty-seven women were randomised to the rapid
      vacuum group and 47 to the stepwise group. MAIN OUTCOME MEASURES: Duration of
      ventouse procedure, effectiveness of methods of application, morbidity of mother
      and infant. RESULTS: There was no significant difference in frequency of
      detachment of the cup after rapid or stepwise application of vacuum. A reduction
      in mean duration of the ventouse procedure of 6 min was realised without
      significant difference in maternal or neonatal morbidity. CONCLUSION: Rapid
      application of vacuum significantly reduces the duration of a ventouse extraction
      procedure without compromise to efficiency and safety.

PMID- 8988694
TI  - Preventing Rhesus D haemolytic disease of the newborn by giving anti-D
      immunoglobulin: are the guidelines being adequately followed?
AB  - OBJECTIVE: To ascertain whether anti-D immunoglobulin is being administered to
      Rhesus D negative women in accordance with the 1991 recommendations for its use
      to cover all events which may result in fetomaternal haemorrhage. DESIGN: The
      notes of women delivered in 1994 were examined for compliance with the 1991
      recommendations. SETTING: Seven maternity units using a central antenatal
      screening service. PARTICIPANTS: Nine hundred and twenty-two Rhesus D negative
      women delivered in these seven hospitals. MAIN OUTCOME MEASURES: The
      prescription, dosage and indications for administration of anti-D immunoglobulin
      to women during pregnancy and in the puerperium. RESULTS: Postnatal anti-D
      immunoglobulin was given in appropriate doses to more than 95% of women who
      required it. Omissions mainly arose from confusion among women who recently had
      received antenatal treatment with anti-D immunoglobulin. The 1991 recommendations
      for antenatal administration were less closely followed. Abdominal trauma was
      covered in only 20% of cases. An inadequate dosage of 250 i.u. was given to 25
      women for antepartum haemorrhage after 20 weeks of gestation. The purpose of the
      Kleihauer test was sometimes poorly understood, with a 'negative' result
      interpreted as a reason not to give anti-D immunoglobulin. CONCLUSION: Closer
      adherence to the 1991 recommendations might further reduce the incidence of
      Rhesus D immunisation below the current 1%. It is suggested that more careful
      application of the recommendations should be evaluated before considering either
      routine antenatal prophylaxis, or the European recommendation of a larger dose
      (1000-1500 i.u.), both of which would increase the requirements for this limited
      resource.

PMID- 8988695
TI  - Counselling implications of chromosomal abnormalities other than trisomy 21
      detected through a maternal serum screening programme.
AB  - OBJECTIVE: To identify counselling requirements, we reviewed the frequency and
      type of non-trisomy 21 chromosome abnormalities found at amniocentesis after
      maternal serum screening for Down's syndrome. DESIGN: The study involved a review
      of the cytogenetic results of amniocenteses performed because of a raised
      maternal serum screening risk. SETTING: The maternal serum screening and
      amniocenteses were performed at hospitals in the Yorkshire region. SAMPLE: 1715
      amniocenteses were performed as a result of a raised maternal serum screening
      risk for the period 1990 to 1993. METHODS: The cytogenetic results were
      classified into the main categories of numerical and structural chromosomal
      abnormalities. MAIN OUTCOME MEASURES: The nature and frequency of abnormal
      cytogenetic results were identified in which parental samples were required in
      order to determine if the abnormal finding was de novo or familial and/or for
      which specialist genetic counselling was required. RESULTS: Sixty-nine
      pregnancies of 1715 amniocenteses were identified with a chromosomal abnormality
      (4.0%): 35 (2.0%) with trisomy 21 and 34 (2.0%) with another chromosomal
      abnormality. For 20 of these 34 abnormalities, parental karyotypes were required
      and in 29 of the 34 specialist genetic counselling was required. CONCLUSIONS:
      Women undergoing maternal serum screening and, in particular, those proceeding to
      amniocentesis, should be informed that there is an equal chance that a
      chromosomal abnormality other than trisomy 21 will be found at amniocentesis, the
      nature of which usually requires parental samples and specialist counselling.

PMID- 8988696
TI  - Faecal incontinence after childbirth.
AB  - OBJECTIVE: To measure the prevalence and severity of postpartum faecal
      incontinence, especially new incontinence, and to identify obstetric risk
      factors. DESIGN: A cohort study with information on symptoms collected in home
      based interviews and obstetric data from hospital casenotes. SETTING: Deliveries
      from a maternity hospital in Birmingham. PARTICIPANTS: Nine hundred and six women
      interviewed a mean of 10 months after delivery. MAIN OUTCOME MEASURES: New faecal
      incontinence starting after the birth, including frank incontinence, soiling and
      urgency. RESULTS: Thirty-six women (4%) developed new faecal incontinence after
      the index birth, 22 of whom had unresolved symptoms. Twenty-seven had symptoms
      several times a week, yet only five consulted a doctor. Among vaginal deliveries,
      forceps and vacuum extraction were the only independent risk factors: 12 (33%) of
      those with new incontinence had an instrumental delivery compared with 114 (14%)
      of the 847 women who had never had faecal incontinence. Six of those with
      incontinence had an emergency caesarean section but none became incontinent after
      elective sections. CONCLUSIONS: Faecal incontinence as an immediate consequence
      of childbirth is more common than previously realised, and medical attention is
      rarely sought. Forceps and vacuum extraction deliveries are risk factors, with no
      protection demonstrated from emergency caesarean section. Identification and
      treatment is a priority.

PMID- 8988697
TI  - Antecedent circumstances surrounding neural tube defect births in 1990-1991. The
      Steering Committee of the National Confidential Enquiry into Counselling for
      Genetic Disorders.
AB  - OBJECTIVE: To investigate births with neural tube defects at a time when most
      districts were screening for the condition. The objective was to document the
      circumstances surrounding each affected birth and assess the care provided
      against given standards. DESIGN: Retrospective review of antenatal casenotes by
      the obstetric team. POPULATION: Three hundred and eight births in England and
      Wales in 1990 to 1991 were reported to the Office of Population Census Survey
      (OPCS) to involve neural tube defects. Sufficient information was available to
      identify both the woman and the obstetrician in 213 pregnancies. Details were
      obtained from a questionnaire completed by the obstetric team for 168 (79%). In
      20/168 cases either the reported outcome was not a live birth/stillbirth or the
      pregnancy did not involve a neural tube defect: eight resulted in a 'normal'
      infant, eight were terminated and in four the abnormality was not a neural tube
      defect. Thus 148 eligible cases were available for analysis. RESULTS: Of the 148
      births, the anomaly was not detected prenatally or detected later than 25 weeks
      of gestation in 98 cases (66%), diagnosed in a multiple pregnancy in 24 (16%) and
      diagnosed prenatally but the woman chose to continue the pregnancy in 26 (18%).
      Of the 98 births not detected prenatally or detected late during pregnancy, the
      surrounding circumstances were that screening was declined in six cases (4%),
      screening was not offered due to late booking in 30 (20%), serum alpha
      fetoprotein screening gave a false negative result in eight (5%), ultrasound
      screening gave a false negative result in 29 (20%), both screening methods gave
      false negative results in 17 (11%) and other reasons in eight (5%). The estimated
      sensitivity of ultrasound screening for anencephaly was 100%. For spina bifida
      the estimated sensitivity for singleton pregnancies is higher for serum alpha
      fetoprotein screening, 84% to 92%, than ultrasound screening, 70% to 84%, for a
      range of assumptions regarding the degree of under-reporting to OPCS of live
      births and terminations. CONCLUSIONS: Late booking precluded the offer of
      screening tests in a substantial proportion (22%) of cases. The presence of
      multiple fetuses including one or more with a neural tube defect was a serious
      additional complication in prenatal screening, diagnosis and counselling.
      Screening for neural tube defects was widespread in 1990 to 1991, although
      variations in the services provided were documented. Ultrasound scanning was a
      major component but was associated with a lower sensitivity than maternal serum
      alpha-fetoprotein screening for neural tube defects other than anencephaly.

PMID- 8988698
TI  - Are sociodemographic factors predictive of preterm birth? A reappraisal of the
      1958 British Perinatal Mortality Survey.
AB  - OBJECTIVE: Reassessment of the predictive value of sociodemographic factors on
      preterm birth. DESIGN: Population-based case-control study. SETTING: England,
      Wales and Scotland. SAMPLE: The study sample consisted of 5630 primiparous and
      9538 multiparous women who were delivered during the first week of March 1958 in
      Britain. Multiple births were excluded. METHOD: Factors potentially predictive of
      preterm birth were assessed for primiparous and multiparous women separately,
      using the split-sample cross-validation technique. MAIN OUTCOME MEASURE: Preterm
      birth, defined as birth occurring before 259 days of gestation. RESULTS: Preterm
      birth rates for primiparous and multiparous women were 54 and 53 per 1000 births,
      respectively. In primiparous women low maternal age (under 20 years) was the only
      sociodemographic variable that was predictive of preterm birth (P = 0.01).
      However, only 10.7% of preterm birth among primiparous women was associated with
      low maternal age. In multiparous women, using univariable analysis, employment
      status was statistically significantly associated with preterm birth. This
      association disappeared when employment status was adjusted for by other
      variables in the model. Social class was not predictive of preterm birth in
      either primiparous or multiparous women. CONCLUSION: From the results of this
      study it is concluded that sociodemographic factors do not have a substantial
      impact on the risk of preterm birth. It seems unlikely that preventative measures
      aimed at social-demographic adversity will reduce preterm birth rates.

PMID- 8988699
TI  - A double-blind randomised controlled trial of the effects of medroxyprogesterone
      acetate on bone density of women taking oestrogen replacement therapy.
AB  - OBJECTIVE: To assess the effects of medroxyprogesterone acetate on bone density
      in women who have had a hysterectomy. DESIGN: Randomised, double-blind, placebo
      controlled trial of medroxyprogesterone acetate 10 mg, 20 mg or placebo as an
      adjunct to oestrogen therapy. PARTICIPANTS: One hundred and twenty-three women,
      aged 18 to 45 years and currently receiving daily oestrogen, who presented at a
      university-based rheumatology practice. INTERVENTIONS: The women were randomly
      assigned to receive either medroxyprogesterone acetate 10 mg, 20 mg or placebo
      daily beginning on day 15 of each month for one year. Forty-one women were
      randomised into each group. MAIN OUTCOME MEASURE: The primary outcome measurement
      was the percentage of change from baseline in bone mineral density of the lumbar
      spine (L2-L4). Secondary outcome measures included differences in femoral neck
      bone density, cholesterol and triglyceride levels between groups. RESULTS: At one
      year, change in bone mineral density did not differ between either the treatment
      or placebo groups. Medroxyprogesterone acetate 20 mg and 10 mg led to
      statistically significant reductions in very low density lipoprotein cholesterol,
      total triglycerides, and very low density lipoprotein triglycerides when compared
      with placebo. Medroxyprogesterone acetate 20 mg also led to a statistically
      significant reduction in high density lipoprotein cholesterol, high density
      lipoprotein-2 cholesterol, and high density lipoprotein-2 triglycerides.
      CONCLUSIONS: Medroxyprogesterone acetate at either dose as an adjunct to
      oestrogen did not improve bone mineral density at one year when compared with
      placebo. Medroxyprogesterone acetate 10 mg may not adversely affect lipids.
      Medroxyprogesterone acetate 20 mg, however, did reduce high density lipoprotein
      cholesterol and therefore may increase cardiovascular risk.

PMID- 8988700
TI  - Laparoscopic sterilisation: opinion and practice among gynaecologists in
      Scotland.
AB  - OBJECTIVES: 1. To produce a list of evidence-based criteria for good quality care
      relating to female laparoscopic sterilisation. 2. To assess the level of
      agreement with each criterion among gynaecologists in Scotland. 3. To obtain an
      overview of current sterilisation practice for comparison with the agreed
      criteria. DESIGN: 1. Agreement with criteria assessed by questionnaire survey; 2.
      Overview of current practice obtained by questionnaire survey and by casenote
      review. SETTING: Scotland. SAMPLE: 1. Questionnaire survey: all 132 consultant
      gynaecologists in NHS practice. 2. casenote review: 988 consecutive women
      sterilised in 12 representative hospitals. RESULTS: The response rate to the
      questionnaire survey was 94%. A list of 15 evidence-based criteria was produced,
      covering patient selection, information and counselling, techniques of tubal
      occlusion and timing of sterilisation. All 15 suggested criteria gained an
      overall balance of support among responding gynaecologists. Similar impressions
      of current practice were gained from the questionnaire survey and from the
      casenote review. Aspects of practice which measured up well to the agreed
      criteria included: only 6% of women sterilised were younger than 25 years of age;
      over 85% of casenotes included clear documentation that women had been counselled
      regarding failure rate and intended permanency; 88% of sterilisations were
      performed, or directly supervised by, a gynaecologist of consultant or senior
      registrar status; and only 2% of sterilisations were undertaken in combination
      with induced abortion. Aspects of practice which compared poorly with the agreed
      criteria, and for which recommendations for change have been made, included: only
      22% of casenotes mentioned that the option of vasectomy had been discussed; only
      30% of gynaecologists indicated that they provide locally produced information
      leaflets as an adjunct to counselling; four methods of tubal occlusion (including
      unipolar diathermy) were in use; and there were wide variations among hospitals
      in the use of day-case care, ranging from 19% to 99%. CONCLUSIONS: A list of
      criteria for good quality care in relation to sterilisation has been validated by
      agreement among Scottish gynaecologists. Current practice (as assessed by
      questionnaire survey and casenote review) has been compared with the criteria and
      some recommendations for change in practice have been made. Following
      dissemination of these results and recommendations, re-audit will be undertaken
      in order to identify any changes.

PMID- 8988701
TI  - Serum levels of the tumour-associated trypsin inhibitor in patients with
      endometriosis.
AB  - OBJECTIVE: To show that in patients with endometriosis a 6 kD polypeptide, the
      tumour-associated trypsin inhibitor (TATI), can occur at elevated concentrations
      in serum. DESIGN: In a prospective study TATI serum levels were assessed prior to
      surgery in 368 consecutive patients suffering from benign gynaecological diseases
      (e.g. pelvic pain, infertility, elective sterilisation, uterine fibroids and
      pelvic masses) with (n = 71) and without (n = 297) endometriosis, who underwent
      laparoscopy or laparotomy for diagnosis and/or treatment. RESULTS: The TATI serum
      levels of patients suffering from endometriosis were significantly different from
      those in the control group and showed a positive correlation with the stage of
      endometriosis. The sensitivity of TATI was 0.34 with a specificity of 0.85 for
      all cases of endometriosis, with an increase of sensitivity (0.67) and slight
      decrease of specificity (0.82), considering only a group of Stage III/IV
      patients. Excluding patients with benign ovarian cysts, the specificity of TATI
      was 0.91 and 0.85, respectively. The combination of TATI and CA125 showed an
      increase of sensitivity to 0.59 for all cases of endometriosis and 0.89 for
      patients with Stage III/IV endometriosis. CONCLUSIONS: The sensitivity of TATI as
      a screening method for endometriosis is too low, but considering its high
      specificity, TATI in combination with CA125 could provide an additional
      diagnostic tool in diagnosis and follow up of patients with endometriosis.

PMID- 8988702
TI  - Posterior colporrhaphy: its effects on bowel and sexual function.
AB  - OBJECTIVE: To determine the anatomical cure rate of posterior colporrhaphy and
      its effect on bowel and sexual function one to six years later. DESIGN:
      Retrospective observational study. SETTING: Urogynaecology Unit, St George's
      Hospital, London. PARTICIPANTS: Two hundred and thirty-one women who underwent
      posterior colporrhaphy. MAIN OUTCOME MEASURES: Anatomical and symptomatic cure of
      rectocoele. METHODS: The charts of 231 women who underwent 244 posterior
      colporrhaphies between 1 January 1989 and 4 January 1994 were reviewed. One
      hundred and seventy one (74%) were interviewed; 140 (61%) were examined. Mean
      follow up time was 42.5 months (range 11-74). RESULTS: Two hundred and nine women
      had prior or concurrent vaginal and/or bladder neck surgery including 38 previous
      posterior colporrhaphies. Postoperatively prolapse symptoms due to rectocoele
      decreased (64% vs 31%). Constipation (22% vs 33%), incomplete bowel emptying (27%
      vs 38%), incontinence of faeces (4% vs 11%) and sexual dysfunction (18% vs 27%)
      increased. Those with incontinence of stool were more likely to have had two or
      more posterior colporrhaphies. Sixty-two percent felt that they improved over all
      after surgery. Additional postoperative symptoms included: vaginal and/or
      perineal splinting (33%), soiling and/or inability to wipe clean (16%), rectal
      digitation (23%), incontinence of flatus (19%), and rectal and/or vaginal pain
      (22%). Thirty-three women (24%) had large rectocoeles, seven of whom did not have
      impaired bowel emptying. CONCLUSIONS: Posterior colporrhaphy corrects the vaginal
      defect in 76% of women. It does not necessarily correct and may contribute to
      bowel and sexual dysfunction, particularly in those requiring multiple
      procedures. The presence of the anatomical defect does not imply dysfunction. The
      prevalence of bowel symptoms suggests the need for close questioning about bowel
      habits and the selective use of bowel investigations for some women before
      surgery.

PMID- 8988703
TI  - Urogenital ageing and its effect on sexual health in older British women.
AB  - OBJECTIVE: To provide information on the extent of problems of urogenital ageing
      in older British women. DESIGN: A MORI survey of a representative population
      sample of older British women. SETTING: Home interviews. PARTICIPANTS: Two
      thousand and forty-five women aged 55-85+. RESULTS: Urogenital symptoms had
      affected 48.8% of the women at some time, but no more than 11% were currently
      affected by individual symptoms; however, these were often of long duration. The
      majority (73%) were not sexually active, with lack of a partner being a factor
      for many. There was also a decreasing prevalence of sexual activity with
      increasing age. Those sexually active in the 65-74 year old age group (n = 148)
      tended to have a similar sexual frequency (at least once per month) compared with
      the younger women studied. Approximately 12% of those who reported dyspareunia
      and/or vaginal dryness claimed a severe problem; 33% did not seek professional
      advice and 36% resorted to an over the counter remedy. Use of hormone replacement
      therapy was generally of relatively short duration. There was a declining
      gradient of ever-use with age. CONCLUSIONS: The extent of significant urogenital
      symptoms is relatively low, but some women are seriously affected and use self
      help as well as professional assistance. The extent of sexual activity in older
      women and factors affecting this have been defined, and the effect of urogenital
      symptoms on sexual activity demonstrated.

PMID- 8988704
TI  - Reversal of sterilisation by the railroad technique.
AB  - OBJECTIVE: To show that a simple, easily learned and relatively inexpensive
      method of reversal of sterilisation provides good results. DESIGN: Retrospective
      observational study. SETTING: An NHS Trust Hospital. SAMPLE: Sixty-seven women
      aged 19 to 39 years who underwent reversal of sterilisation between January 1984
      and December 1993. MAIN OUTCOME MEASURES: Pregnancy rate following reversal; rate
      of ectopic pregnancy. RESULTS: Thirty-four women (51%) had intrauterine
      pregnancies after reversal of sterilisation; intrauterine pregnancy rate in women
      who had been sterilised with rings or clips was 64%. Five women (7.5%) had
      ectopic pregnancies. CONCLUSION: This technique provides results that compare
      favourably with those of microsurgery. It offers hope to couples who do not meet
      the restrictive criteria for microsurgery and in vitro fertilisation and should
      appeal to purchasing authorities.

PMID- 8988705
TI  - GAX collagen in the treatment of urinary incontinence in elderly women: a two
      year follow up.
AB  - OBJECTIVE: To determine the efficacy of GAX collagen in the treatment of elderly
      women with genuine stress incontinence. DESIGN: A single centre prospective
      study. SETTING: A London teaching hospital. PARTICIPANTS: Thirty-four women older
      than 60 years of age with genuine stress incontinence diagnosed on
      videocystourethrography. INTERVENTIONS: Up to three paraurethral injections of
      GAX collagen. MAIN OUTCOME MEASURES: Subjective and pad test assessments
      performed pre-operatively, after one month, one year and two years after the
      first injection of collagen. Videocystourethrography and urethral pressure
      profilometry were carried out pre-operatively, after three months and one year.
      RESULTS: There was a reduction in urinary leakage as measured on pad testing.
      After two years 77% of the surviving 26 women were symptomatically cured.
      Objectively after two years 48% of the women were cured and 9% were improved over
      their initial pre-treatment level of incontinence. The cure rate was the same
      whether or not the women had undergone previous vaginal surgery. The maximum
      urethral closure pressure was not increased with treatment indicating that
      collagen injections do not act by producing obstruction, but this should be
      interpreted with caution due to the small sample size. CONCLUSION: GAX collagen
      is an effective method of treating urinary incontinence in the elderly and
      especially women who have undergone previous continence procedures. The technique
      is easy to perform and particularly suitable in those who are frail, but if
      failure occurs after two years consideration needs to be given to its cost
      effectiveness.

PMID- 8988706
TI  - Investigation of 100 consecutive negative cone biopsies.
AB  - OBJECTIVE: To investigate the reasons for cone biopsies reported as not
      containing intraepithelial or invasive malignancy and thereby find ways to
      decrease their incidence. DESIGN: One hundred cone biopsies reported as negative
      were identified out of a total of 436 consecutive cone biopsies. The patients'
      cytology, colposcopy and histology reports and cytology and histology slides were
      reviewed. Further opinions in cases of doubt were obtained in cytology and
      histology. In cone biopsies still considered negative after reviews, deeper
      levels were cut, exhausting all paraffin blocks. Follow up cytology, colposcopy
      and histology were reviewed. SETTING: Gynaecological oncology unit in a
      university teaching hospital. RESULTS: After re-evaluation the final diagnoses of
      cone biopsies initially reported as negative were positive (n = 21),
      unsatisfactory (n = 27) and true negative (n = 51), with one case excluded
      because of insufficient material for review. The positive cases were diagnosed on
      review (n = 11) or extra levels (n = 10). The unsatisfactory cases were all due
      to denudation. The 51 true negative cases were divided into those which never had
      had histologic confirmation by punch biopsy or endocervical curettage (n = 47)
      and those with a previously confirmed histological abnormality (n = 4).
      CONCLUSIONS: The number of negative cone biopsies can be reduced by: 1. taking
      Pap smears after correction of atrophy and inflammation; 2. more scrupulous
      colposcopy aimed at reducing the number of unsatisfactory colposcopies or
      misinterpreted colposcopic findings; this through examination should include the
      vagina and vulva; 3. confirmation of smear and colposcopic findings by biopsy
      prior to cold-knife conisation and performing a large loop excision of the
      transformation zone (LLETZ) for cases where there is a discrepancy between the
      smear abnormality and colposcopy/biopsy findings; 4. good quality cone biopsies
      using a technique that does not handle the mucosa and is performed after the
      mucosa has had time to regenerate following the colposcopic investigations; and
      5. exhausting all blocks with multiple levels before reporting a cone biopsy as
      negative.

PMID- 8988707
TI  - Gestational trophoblastic disease with liver metastases: the Charing Cross
      experience.
AB  - OBJECTIVE: To define management options for women presenting with gestational
      trophoblastic disease (GTD) which had already metastasised to the liver. DESIGN:
      Retrospective analysis of case records between 1958 and 1994. SETTING: A national
      referral centre for trophoblastic disease. RESULTS: The database containing 1676
      treated patients was reviewed and 46 patients with hepatic metastases were
      identified (2.7%). The median age was 32 years (range 19-52 years). The
      antecedent pregnancy to the GTD was normal in 65% (30/46), and the time interval
      between the antecedent pregnancy and presentation was longer than one year in 50%
      (22/44). Lung metastases were present in 43 patients (93%) and brain deposits in
      15 patients (33%). Forty-five patients (98%) were high risk by WHO criteria. The
      five-year overall survival was 27%. The five-year survival of the subgroup of
      patients having both hepatic and cerebral metastases was 10%. There was no
      significant survival difference between the different chemotherapy regimens used
      in the study period (pre-1979 CHAMOCA: methotrexate, actinomycin D,
      cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine; 1979
      onwards EMA/CO-EP: etoposide, methotrexate, adriamycin-D/ cyclophosphamide,
      vincristine-etoposide and cis-platinum). Multivariate analysis revealed that a
      prognostic score > 12 was significant (Hazard ratio 5.4, 95% CI 0.7-41.9; P =
      0.04). CONCLUSIONS: The outcome for women presenting with hepatic metastases from
      GTD is poor with an even worse prognosis if cerebral metastases are also present.
      Alternative therapeutic measures, such as high dose therapy or new drugs, should
      be explored in these women.

PMID- 8988708
TI  - Local immune response in endometrial carcinomas.
AB  - OBJECTIVE: To determine whether Langerhans cells act as antigen-presenting cells
      in endometrial carcinomas and their related lesions. SAMPLES: Frozen endometrial
      samples were obtained from 13 women with normal menstrual cycles, 3
      postmenopausal women, 11 women with hyperplasia (simple 4, complex 4 and atypical
      3) and 32 women with endometrial carcinomas. MAIN OUTCOME MEASURES: Langerhans
      cells (CD1), T lymphocytes (CD4 and CD8), B lymphocytes (CD22), natural killer
      (NK) cells (CD57) and HLA-DR were all quantitatively assessed in endometrial
      samples using immunohistochemical method. RESULTS: The numbers of Langerhans,
      CD4+, CD8+ and B cells were higher in the secretory phase than in the
      proliferative endometrium. The CD8+ cells appeared to be more plentiful than the
      CD4+ cells. When compared with the proliferative endometrium, the numbers of
      Langerhans cells were higher in hyperplasias and carcinomas. Most of Langerhans
      cells were HLA-DR+, showing a strong correlation with CD4+ cells in carcinomas.
      This suggests that MHC class II antigen restricted lymphocytes in carcinomas are
      activated by HLA-DR+ Langerhans cells. However, epithelial expression of HLA-DR
      in carcinomas did not show on association with high numbers of Langerhans and
      CD4+ cells. No correlation was observed between Langerhans cells and
      clinicopathologic features of carcinomas. In contrast, the number of NK cells
      significantly decreased in noninvasive carcinomas but increased in Grade 3
      tumours. CONCLUSION: Based on the above findings, Langerhans cells are considered
      to act as antigen-presenting cells in carcinomas, but it was not shown that they
      were activated by epithelial expression of HLA-DR in carcinomas.

PMID- 8988710
TI  - An unusual case of cystolithiasis: a urological lesson for gynaecologists.

PMID- 8988709
TI  - Use of magnesium sulphate in Scottish obstetric units.
AB  - The greater efficacy of magnesium sulphate compared with diazepam or phenytoin in
      the treatment of eclampsia is now generally accepted. We used a postal
      questionnaire to establish the frequency and nature of use of magnesium sulphate
      in obstetric units in Scotland. Ninety percent of units responded and of these
      90% were either using the drug or intended to do so. There was considerable
      heterogeneity in the indications for its use and some important omissions in the
      monitoring of patients receiving the drug. The introduction of magnesium sulphate
      for a rare indication to units with no previous experience of its use may be
      associated with significant risks to obstetric patients.

PMID- 8988711
TI  - The relation between serum markers in the second trimester and placental
      pathology. A study on extremely small for gestational age fetuses.

PMID- 8988712
TI  - Active mismanagement of labour.

PMID- 8988713
TI  - Randomised evaluation of a prototype suction fetal scalp electrode.

PMID- 8988714
TI  - Fetal size at birth in relation to quality of blood glucose control in
      pregnancies complicated by pregestational diabetes mellitus.

PMID- 8988715
TI  - Birth under water--to breathe or not to breathe.

PMID- 8988716
TI  - Differentiation of growth retarded from normally grown fetuses and prediction of
      intrauterine growth retardation using Doppler ultrasound.

PMID- 8988717
TI  - Risk factors and fetal outcome in cases of shoulder dystocia compared with normal
      deliveries of a similar birthweight.

PMID- 8988718
TI  - Is there any value in the long-term follow up of women treated for endometrial
      cancer?

PMID- 8988719
TI  - Breast carcinoma mortality rates and screening.

PMID- 8988720
TI  - Helicobacter pylori and primary gastric lymphoma. A histopathologic and
      immunohistochemical analysis of 237 patients.
AB  - BACKGROUND: Few previous articles have analyzed the relation between infection
      with Helicobacter pylori (H. pylori) and primary gastric lymphoma in a large
      number of patients. METHODS: Resected and biopsied specimens from 237 patients
      with primary gastric lymphoma were investigated for H. pylori using hematoxylin
      and eosin stain, modified Giemsa stain, and immunohistochemistry. These specimens
      were compared with specimens from 29 patients with chronic active gastritis, 33
      with peptic ulcers, and 41 with gastric carcinoma. RESULTS: H. pylori was
      detected in 145 of 237 patients (61%) with gastric lymphoma. The frequency of H.
      pylori positivity was higher in patients with lymphoma restricted to the mucosa
      and submucosa (76%) than in those with lymphoma invading beyond the submucosa
      (48%) (P < 0.001), and was also higher in patients with low grade mucosa
      associated lymphoid tissue lymphoma (72%) than in those with high grade tumors
      (55%) (P < 0.05). The frequency of H. pylori positivity in patients with lymphoma
      was lower than in those with chronic active gastritis (100%) (P < 0.001) or
      peptic ulcer (91%) (P < 0.05). In patients with lymphoma restricted to the mucosa
      and the superficial portion of the submucosa, the frequency of H. pylori
      positivity (90%) was as high as that observed in patients with chronic active
      gastritis and peptic ulcer. The H. pylori grading score for patients with
      lymphoma (0.9 +/- 1.0) was lower than for those with chronic active gastritis
      (1.9 +/- 0.8) (P < 0.001), peptic ulcers (2.2 +/- 1.0) (P < 0.001), or gastric
      carcinoma (1.2 +/- 1.1) (P < 0.05). CONCLUSIONS: These results suggest that H.
      pylori is more likely to be associated with early states of primary gastric
      lymphoma than with advanced states. Thus, H. pylori may disappear during the
      progression of primary gastric lymphoma.

PMID- 8988721
TI  - Enhanced induction of apoptosis of human gastric carcinoma cells after
      preoperative treatment with 5-fluorouracil.
AB  - BACKGROUND: It has been reported that anticancer drugs induce apoptosis, thus it
      is considered that apoptosis may be important in cancer chemotherapy. The authors
      examined whether the administration of 5-fluorouracil (5-FU) enhanced apoptosis
      of gastric carcinoma cells, and investigated the relationship between apoptosis
      and the expression of Ki-67 and the Bax gene. METHODS: Twenty patients with
      gastric carcinoma were divided into 2 groups. Ten patients received continuous
      intravenous 5-FU at 500 mg/body weight/day for 7 days preoperatively whereas the
      other 10 did not receive any chemotherapy or radiotherapy, and served as
      controls. For detection of apoptotic cells, apoptotic indices were examined by
      the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      biotin nick end labeling (TUNEL) method. The expression of Ki-67 and the Bax gene
      were examined by immunohistochemical staining. RESULTS: Apoptosis of gastric
      carcinoma cells increased significantly to 6.1 +/- 3.6% in the 5-FU-treated group
      compared with the controls (3.2 +/- 1.8%; P < 0.05). The level of expression of
      Ki-67, a marker of cell proliferation, was inversely correlated with the extent
      of TUNEL staining that was specific for apoptosis. The percentage of cells that
      were immunopositive for Ki-67 fell to 50.8 +/- 7.3% of the apoptotic area in the
      5-FU-treated group compared with 57.5 +/- 6.9% in the controls (P < 0.05). There
      was no significant correlation between frequency of apoptotic cells and the level
      of expression of the Bax gene. CONCLUSIONS: The authors demonstrated enhanced
      apoptosis in gastric tumors after continuous intravenous infusion of 5-FU for 7
      days. This result suggests that it may be possible to evaluate the effects of
      chemotherapy by detecting apoptotic cells.

PMID- 8988722
TI  - Anorectal malignant melanoma. A clinicopathologic study, including
      immunohistochemistry and DNA flow cytometry.
AB  - BACKGROUND: Anorectal malignant melanoma is a rare tumor with an extremely poor
      prognosis. DNA flow cytometric study as well as detailed immunohistochemical
      study have not been reported previously. METHODS: Eighteen cases of anorectal
      melanoma were studied, including immunohistology for melanoma markers and
      epithelial markers and DNA flow cytometric study of paraffin blocks. RESULTS:
      Most patients were Ashkenazi Jews, compared with Sephardi Jews and Arabs. Of the
      17 patients followed, 14 died of disease at 4-39 months from presentation. Three
      patients were alive with disease at 12, 53, and 72 months of follow-up. Tumor
      thickness ranged from 3-35 mm (mean, 12.8 mm). The 2 long term survivors had
      tumor thickness < or = 7 mm. No correlation was found between the mode of primary
      surgical treatment (8 patients: abdominoperineal resection; 10 patients: local
      excision) and outcome. Vimentin, HMB-45, and S-100 protein stainings were
      positive in 18, 17, and 15 tumors, respectively. Polyclonal carcinoembryonic
      antigen (CEA), broad-spectrum cytokeratin, epithelial membrane antigen,
      monoclonal CEA, and TAG-72 (B72.3) stainings were positive in 13, 3 (only focal
      and rare staining), 2, 0, and 0 tumors, respectively. Thirteen tumors had
      adequate material for DNA analysis, and all were DNA aneuploid. S-phase fraction
      could be assessed in 11 tumors and ranged from 7.7-24% (mean, 14%). An S-phase
      fraction of < 10% was observed in the 2 long term survivors. CONCLUSIONS:
      Anorectal melanoma in this study carried a grave prognosis. The frequent staining
      for polyclonal CEA (with negative monoclonal CEA staining) was probably due to
      nonspecific cross-reacting antigens. The occasional staining for epithelial
      markers warrants a comprehensive immunohistochemical study to ensure a correct
      diagnosis, especially in small biopsies of amelanotic undifferentiated tumors
      that lack junctional changes. The aneuploidy of all tested tumors reflected their
      highly malignant behavior. A trend toward longer survival was observed in
      patients with thin tumors and an S-phase fraction of < 10%. However, due to the
      small number of survivors, the latter observation should be further tested in a
      larger scale series.

PMID- 8988723
TI  - What constitutes long-term survival after surgery for hilar cholangiocarcinoma?
AB  - BACKGROUND: Hilar cholangiocarcinomas are rarely considered to be resectable and
      specific data regarding long-term survival are not available. METHODS: A
      retrospective single center experience from 1971 and 1995 details long-term
      survival among 339 patients who underwent surgery for adenocarcinoma of the
      hepatic duct bifurcation. Tumor removal was accomplished by resection of the bile
      duct bifurcation either alone (33 patients), in combination with hepatic
      resection (77 patients), or combined with hepatic and vascular resection (41
      patients). Thirty-two patients underwent total hepatectomy and liver
      transplantation. In 188 patients the tumor was unresectable and palliative
      internal or external biliary drainage was established. The resectability rate was
      49.2% and rose to 54% after inclusion of liver transplantation. The
      clinicopathologic features of 32 5-year survivors were compared with patients
      whose survival was less than 5 years. RESULTS: Thirty-two patients survived
      longer than 5 years after surgical treatment of hilar cholangiocarcinoma; 22 of
      these patients (69%) were still alive at last follow-up. Twenty-six long-term
      survivors had primarily undergone resection; 4 received liver transplants. There
      was 1 long-term survivor beyond 5 years after both exploratory laparotomy and
      subsequent percutaneous transhepatic drainage, and palliative hepatojejunostomy.
      Long-term survival after resection was significantly associated with less
      advanced tumor stages. Lymph node involvement and residual tumor were the primary
      prognostic factors both in a multivariate analysis after resection and in the
      cohort of long-term survivors. Nevertheless, long-term survivors were still at a
      significant risk to die from tumor recurrence. CONCLUSIONS: Radical resection
      offers the best possibility of prolonged survival with a good quality of life for
      patients with hilar cholangiocarcinoma.

PMID- 8988724
TI  - Ectopic production and processing of atrial natriuretic peptide in a small cell
      lung carcinoma cell line and tumor from a patient with hyponatremia.
AB  - BACKGROUND: Tumors and tumor cell lines from two patients with small cell lung
      carcinoma (SCLC) (one with and one without hyponatremia) were studied. Ectopic
      production and prohormone processing of atrial natriuretic peptide (ANP) were
      investigated to determine if a biologically active peptide was produced in a
      tumor cell line from a patient with hyponatremia and no evidence of arginine
      vasopressin (AVP) production. METHODS: Ribonuclease (RNase) protection assays
      were performed on mRNA isolated from tumors and tumor cell lines established from
      two SCLC patients, one with and one without hyponatremia. Cellular extracts and
      conditioned media were studied using reversed-phase high performance liquid
      chromatography (HPLC) to determine the immunoreactive form of ANP. Tumor cell
      line sonicates were studied for subcellular localization of enzymatic activity
      that cleaved pro-ANP peptide substrates. RESULTS: RNase protection assays showed
      a 200-base pair protected fragment in the mRNA isolated from the tumor and tumor
      cell line from the patient with hyponatremia (Patient 4). HPLC characterization
      of the cellular extract and conditioned medium from the tumor and tumor cell line
      from Patient 4 demonstrated ANP immunoreactivity in the same fraction as ANP-
      (S99-Y126). The tumor cell line extract that localizes to a subcellular fraction
      enriched for lysosomes and secretory organelles contains a 60-kilodalton
      molecular weight protein with enzyme activity that hydrolyzes synthetic pro-ANP
      substrates and catalyzes the formation of ANP-(S99-Y126). CONCLUSIONS: A tumor
      cell line from a patient with hyponatremia was able ectopically to produce,
      process, and secrete ANP in the same immunoreactive form as the biologically
      active molecule. Preliminary studies show that tumor cell line NCI-H1284 contains
      an enzyme that can cleave precursors at the same amino acid sequences needed to
      produce ANP-(S99-Y126) from pro-ANP.

PMID- 8988725
TI  - Lung carcinoma in African Americans and whites. A population-based study in
      metropolitan Detroit, Michigan.
AB  - BACKGROUND: African Americans are at higher risk for lung carcinoma than whites
      in the United States. This racial disparity is greater among younger people. The
      authors evaluated whether racial differences in lung carcinoma risk can be
      explained by differences in cigarette smoking behaviors. METHODS: For this study,
      5588 population-based cases of African Americans and whites with pathologically
      confirmed lung carcinoma, diagnosed between 1984 and 1987, were identified
      through the Metropolitan Detroit Cancer Surveillance System. Also identified were
      3692 population-based controls. Logistic regression methods were used to evaluate
      the risk of lung carcinoma associated with race both within cigarette smoking
      category and after adjustment for cigarette-smoking behaviors. RESULTS: The
      difference in lung carcinoma incidence between African Americans and whites was
      explained almost entirely by differences in smoking habits among study
      participants age 55-84 years. However, among males age 40-54 years, African
      Americans were 2-4 times more likely to develop lung carcinoma of any histologic
      type than whites even after adjustments were made for smoking habits. Similar
      excesses in risk among African American females age 40-54 years were demonstrated
      only for squamous cell and small cell carcinomas (odds ratios [OR] and 95%
      confidence intervals [CI] = 3.7 [1.5-8.9] and 2.7 [1-7.3], respectively). Also,
      in this younger age group, African American male nonsmokers and smokers of 1-40
      pack-years had a significantly higher risk of lung carcinoma than white males
      belonging to the same age group with a similar cigarette-smoking history (ORs and
      95% CIs = 8 [2-32.8] and 3.1 [1.9-5.4] respectively). CONCLUSIONS: Elevated risk
      for lung carcinoma among younger (but not among older) African Americans,
      particularly among males, exists both within cigarette smoking exposure level and
      beyond that associated with smoking habits. This may indicate a high risk group
      particularly susceptible to lung carcinogens, or it may indicate unique exposures
      not yet identified.

PMID- 8988726
TI  - Expression of plasminogen activators and plasminogen activator inhibitor 1 in
      dedifferentiated chondrosarcoma.
AB  - BACKGROUND: The plasminogen activator system plays an important role in different
      malignant tumors. These enzymes participate in the destruction of intercellular
      matrices and basement membranes and/or can modulate the growth potency of tumor
      cells and may even promote metastases. In this study, the expression of three
      glycoproteins that play a role in the plasminogen activator system as activators
      of proteolysis-urokinase type plasminogen activator (u-PA), tissue type
      plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1)
      were studied in various components of dedifferentiated chondrosarcomas of bone.
      METHODS: The expression of u-PA, t-PA, and PAI-1 was investigated in 10
      dedifferentiated chondrosarcomas and 14 conventional chondrosarcomas. The
      plasminogen activator/inhibitor glycoproteins were visualized
      immunohistochemically on paraffin sections and the levels of expression were
      assessed semiquantitatively. RESULTS: In dedifferentiated chondrosarcoma, high
      grade dedifferentiated components displayed strong, diffuse coexpression of u-PA,
      t-PA, and PAI-1. For all glycoproteins studied, the immunoreactivity was
      significantly increased compared with the reactions in the low grade
      cartilaginous component of the same tumor and conventional chondrosarcoma. In the
      latter, u-PA, t-PA, and PAI-1 expression was found to be enhanced at invasive
      foci and in regions of endochondral ossification. CONCLUSIONS: The current study
      documents the overexpression of u-PA, t-PA, and PAI-1 in dedifferentiated
      chondrosarcoma and suggests involvement of the plasminogen activator system in
      the biology of these tumors.

PMID- 8988727
TI  - High antileukemic activity of sequential high dose cytosine arabinoside and
      mitoxantrone in patients with refractory acute leukemias. Results of a clinical
      phase II study.
AB  - BACKGROUND: The current study was initiated to assess the efficacy and side
      effects of a timed sequential application of high dose cytosine arabinoside
      (AraC) in combination with mitoxantrone (S-HAM) in patients with refractory acute
      myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). METHODS: Patients
      with refractory AML or ALL were eligible for S-HAM salvage therapy, which was
      comprised of AraC, 1 g/m2 or 3 g/m2 every 12 hours, on Days 1, 2, 8, and 9 and
      mitoxantrone, 10 mg/m2/day, given on Days 3, 4, 10, and 11. RESULTS: Of 22 fully
      evaluable patients, 14 patients (64%) achieved a complete remission whereas 5
      patients (23%) succumbed to early death and 3 patients (14%) did not respond.
      Blood counts recovered at a median of 33.5 days after the start of treatment and
      complete remission was achieved after a median of 38 days. The median duration of
      complete remission was 4 months (range, 1-14 months) whereas overall survival
      time lasted for a median of 4.5 months (range, 1-30+ months). Treatment
      associated toxicity was comprised predominantly of infection and diarrhea that
      reached World Health Organization Grades 3 and 4 in 64% and 32% of patients,
      respectively. Complementary pharmacokinetic evaluations of plasma AraC and AraU
      levels revealed no impact of initial AraC administration on the pharmacokinetics
      of subsequent AraC administrations and failed to demonstrate any evidence of self
      potentiation. CONCLUSIONS: The clinical data show the S-HAM regimen to be a
      promising approach for the treatment of patients with advanced acute leukemias.
      However, further evaluation at earlier stages of treatment is needed.

PMID- 8988728
TI  - Increasing incidence of and declining mortality from breast carcinoma. Trends in
      Malmo, Sweden, 1961-1992.
AB  - BACKGROUND: The incidence of breast carcinoma is increasing in most populations,
      whereas mortality caused by this disease is fairly constant. The authors analyzed
      the incidence of and mortality from invasive breast carcinoma in a population
      with access to good medical care, into which mammographic screening was
      introduced in 1976 and adjuvant therapy in 1978. METHODS: In a consecutive series
      of patients with invasive breast carcinoma from Malmo, 1961-1991, changes in age
      adjusted incidence were analyzed and compared with incidence of the disease in
      the rest of Sweden. Age-adjusted breast carcinoma mortality was studied for the
      period 1964-1992. RESULTS: The introduction of mammographic screening was
      associated with an increase in breast carcinoma incidence. This was restricted to
      the age group that was eligible for screening (age 45-69 years) and to Stage I
      disease. Between 1977 and 1992, age-adjusted breast carcinoma mortality decreased
      in Malmo by 43% (95% CI, 26-56%) as compared with 12% (95% CI, 8-16%) in the rest
      of Sweden. The decrease was statistically significant in both populations and
      significantly greater in Malmo than in the rest of Sweden (P < 0.001). In Malmo
      the decrease was seen in two age groups, age 45-69 years and age 70 years and
      older. In the rest of Sweden the decrease was seen only among women age 70 years
      and older. In the rest of Sweden the decrease was seen only among women age 70
      years and older. There were no changes in incidence or mortality among women
      younger than 45 years in either population. CONCLUSIONS: Breast carcinoma
      incidence was strongly related to diagnostic activity, especially mammographic
      screening. The decrease in mortality occurred in temporal relation to the
      introduction of screening and adjuvant therapy, making a causal relation likely.
      The difference in results between Malmo and the rest of Sweden indicates an
      important role for screening in mortality reduction.

PMID- 8988729
TI  - Evidence of increased failure in the treatment of prostate carcinoma patients who
      have perineural invasion treated with three-dimensional conformal radiation
      therapy.
AB  - BACKGROUND: The detection of perineural invasion (PNI) in the diagnostic
      transrectal biopsy of the prostate is associated with a 93% frequency of
      extracapsular disease extension in patients treated by prostatectomy for
      adenocarcinoma of the prostate. Extracapsular extension is associated with an
      inferior outcome compared with that of patients who have organ-confined disease.
      This study examined the association of PNI and treatment failure in a consecutive
      series of patients treated with three-dimensional conformal radiation therapy
      (3DCRT) alone. METHODS: The authors report actuarial biochemical no evidence of
      disease (bNED) survival rates for 484 consecutive patients with clinically
      localized prostate carcinoma diagnosed by transrectal needle biopsy who completed
      3DCRT alone between May 1989 and December 1994. The median follow-up time was 28
      months (range, 2-75 months), and the median dose to the center of the prostate
      was 7368 centigray (cGy) (range, 6316-8074 cGy). Patients were subdivided into 2
      groups according to pretreatment prostate specific antigen (PSA) levels (< 20
      ng/mL vs. > or = 20 ng/mL). Pathology records were reviewed for the presence or
      absence of PNI. bNED failure was defined as a PSA level > or = 1.5 ng/mL and
      rising on 2 consecutive occasions. bNED survival rates were calculated using
      Kaplan-Meier methodology and comparisons of survival curves were accomplished
      using the log rank test. RESULTS: The 3-year bNED survival for all 484 patients
      was 77%. The presence of PNI predicted decreased bNED survival in all patients.
      This detrimental effect, however, was confined to patients with pretreatment PSA
      values < 20 ng/mL. The bNED survival rates for patients with pretreatment PSA <
      20 ng/mL demonstrated a highly significant decrease if PNI was present versus
      when it was absent (65% vs. 88% at 3 years, 39% vs. 65% at 5 years; P = 0.0009
      for overall curve comparison). For patients with pretreatment PSA < 20 ng/mL,
      multivariate analysis of prognostic variables demonstrated a significant
      association between bNED survival and PNI (P = 0.002), palpation stage (P =
      0.02), and pretreatment PSA (P = 0.006). Gleason score, age, and dose were not
      independent predictors of bNED survival in this group of patients. CONCLUSIONS:
      To the authors' knowledge, this is the first report demonstrating that PNI
      detected on diagnostic transrectal biopsy is a significant predictor of decreased
      bNED survival in patients treated with radiotherapy. The subgroup of patients
      affected are those with pretreatment PSA < 20 ng/mL. This result suggests that
      such patients may benefit from more aggressive treatment, particularly the use of
      larger planning target volumes or adjuvant therapies.

PMID- 8988730
TI  - Evaluation of radiation effect, tumor differentiation, and prostate specific
      antigen staining in sequential prostate biopsies after external beam radiotherapy
      for patients with prostate carcinoma.
AB  - BACKGROUND: Sequential systematic biopsies after radiotherapy (RT) for prostate
      carcinoma were evaluated with respect to radiation effect, tumor differentiation,
      and prostate specific antigen (PSA) staining, and these histopathologic
      parameters were correlated with local outcome. METHODS: Since 1990, transrectal
      ultrasound-guided biopsies have been used to follow patients with localized
      prostate carcinoma after radical external RT at the General Hospital division of
      the Ottawa Regional Cancer Centre. Eighty-nine patients with residual tumor in 1
      or more biopsies at 10-78 months of follow-up were selected for review. All
      patients had undergone biopsy on more than one occasion. The 198 biopsies were
      stained for PSA, high molecular weight keratin, and proliferative cell nuclear
      antigen (PCNA). Therapy effect was graded by nuclear and cytoplasmic changes.
      RESULTS: Of these 89 selected patients, 25 progressed to local failure (LF), 38
      had delayed tumor clearance, and 26 remained biopsy positive without local or
      biochemical progression. In the 24- and 36-month biopsies, RT effect correlated
      with mean nadir serum PSA (Grade 4-6 RT effect: 0.7 ng/mL; Grade 0-3 RT effect:
      1.3 ng/mL [P = 0.01]) and with local outcome (Grade 0-2 RT effect: 55% LF; Grade
      3-4 RT effect: 30% LF; and Grade 5-6 RT effect: 0% LF [P = 0.003]). Of tumors
      with minimal RT effect, 61% were PCNA positive, compared with 34% for moderate
      and 17% for marked RT effect (P < 0.001). Adjacent areas within biopsies showed
      varied RT effect in 27 patients, of whom 41% had local failure, compared with 18%
      of patients with uniform RT effect (P = 0.03). Gleason score was assigned only if
      RT effect was minimal (36 patients/59 biopsies); 74% had the same Gleason score
      (+/-1) as the original, whereas 23% were 2 points lower. Only 1 biopsy lost PSA
      staining completely and 10% stained faintly, whereas 34% stained moderately and
      55% strongly. CONCLUSIONS: PSA staining is apparently retained in residual tumor
      after RT, despite obvious RT effect. RT effect correlates with serum PSA nadir,
      PCNA staining, and local outcome. Varied RT effect is commonly observed in
      biopsies, and correlates with local failure. There is no convincing evidence for
      tumor dedifferentiation after RT.

PMID- 8988731
TI  - The ratio of free to total serum prostate specific antigen and its use in
      differential diagnosis of prostate carcinoma in Japan.
AB  - BACKGROUND: To improve the clinical usefulness of prostate specific antigen
      (PSA), unique methods have been proposed. The percentage of free PSA in serum
      facilitates the distinction between benign histologic conditions and prostate
      carcinoma while retaining high sensitivity. METHODS: Using monoclonal antibodies,
      an AIA total PSA assay system was established that recognized PSA equally in free
      or complex form. The clinical usefulness of the ratio of two different molecular
      forms of PSA was investigated using 268 archival serum samples. RESULTS: Men with
      prostate carcinoma had significantly lower ratios of free to total PSA than those
      with benign prostatic hyperplasia (BPH) (P = 0.0001). At total PSA levels between
      2.1 and 10 ng/mL, medians of total PSA were not significantly different between
      men with prostate carcinoma and men with BPH. Differences in median percentages
      of free PSA for these two groups were statistically significant (P = 0.0001). The
      ratio of free to total PSA was useful for identifying prostate carcinoma in
      palpably benign glands with total PSA of 2.1-10 ng/mL (P = 0.0001), whereas total
      PSA was not useful for such identification. When calculated for low total PSA
      levels between 2.1 and 4 ng/mL, sensitivity and specificity were 91.7% and 72.2%,
      respectively, with a cutoff value of 17%. This ratio of free to total PSA was as
      useful as PSA density in receiver-operating curve analysis. CONCLUSIONS: The use
      of the ratio of free to total PSA renders total PSA of greater use of
      distinguishing prostate carcinoma and is applicable to patients with low total
      PSA. Elderly men with a clinical diagnosis of BPH who are scheduled for surgery
      may benefit from the determination of this ratio.

PMID- 8988732
TI  - Trends in prostate carcinoma incidence in Connecticut (1988-1994) by age and
      race.
AB  - BACKGROUND: Large increases in prostate carcinoma incidence rates from 1988 to
      1992, followed by sharp declines, in several U.S. cancer registries have been
      attributed to the impact of screening. Trends may vary by age, racial and/or
      ethnic group, and geography. METHODS: Trends in prostate carcinoma incidence
      rates between 1988 and 1994 were examined by age group and race (African American
      and white), using data from the population-based Connecticut Tumor Registry.
      RESULTS: Incidence rates for all stages combined rose from 1988 to 1992 and then
      declined for men age 65-74, 75-84, and 85 + years; however, as of 1994, no
      decline was evident for those age 45-54 and 55-64 years. Distant stage rates
      declined after 1991 for men age 65-74 and older, but not for younger age groups
      (in which increases in rates had occurred for all tumor grades among locoregional
      stage cancers). Trends in age-standardized rates were similar for African
      Americans and whites in Connecticut, but larger increases in Utah suggested
      regional differences in screening rates. CONCLUSIONS: Temporal trends in prostate
      carcinoma incidence in elderly men in Connecticut were consistent with the impact
      of screening, but the explanation for trends in younger men was less clear,
      indicating the need for continued monitoring.

PMID- 8988733
TI  - The influence of prostate volume on the ratio of free to total prostate specific
      antigen in serum of patients with prostate carcinoma and benign prostate
      hyperplasia.
AB  - BACKGROUND: Determining the ratio of free to total prostate specific antigen (f
      PSA to t-PSA, calculated as the percentage of f-PSA [f-PSA%]) in serum allow for
      a clearer distinction between patients with prostate carcinoma (PCa) and patients
      with benign prostate hyperplasia (BPH) than determining the level of t-PSA alone.
      To find influencing factors on f-PSA%, the authors investigated prostate volume,
      TNM classification, and tumor stage. METHODS: The authors measured f-PSA and t
      PSA in 36 men with untreated PCa (tumor classification: T1, 2, 3pNO, MO), 44
      patients with BPH, and 54 healthy controls. Prostate volume was determined by
      transrectal ultrasound. RESULTS: The median values of t-PSA and f-PSA% were 7.8
      micrograms/L and 10.5% in PCa patients, 4.3 micrograms/L and 20.8% in patients
      with BPH, and 1.4 micrograms/L and 23.6% in the control group. Patients with PCa
      had a significantly lower proportion of f-PSA than BPH patients and healthy men.
      There was no correlation of f-PSA% to TNM stage or tumor grade. In PCa patients a
      significant positive correlation (correlation coefficient [r] = 0.51, P < 0.001)
      was found between f-PSA% and prostate volume, whereas there was no significant
      correlation in BPH patients (r = -0.27, P > 0.05). There was a significant
      difference in f-PSA% between PCa and BPH patients with prostate volumes smaller
      than 40 cm3 (9.0% vs. 21.6%, P < 0.01) but not between patients in these 2 groups
      with prostate volumes exceeding 40 cm3 (15.1% vs. 18.2%, P = 0.11). CONCLUSIONS:
      Determining the ratio of f-PSA to t-PSA to discriminate between PCa and BPH
      patients yields significant results only in men with a prostate volume of less
      than 40 cm3.

PMID- 8988734
TI  - Vinblastine, ifosfamide, and gallium nitrate--an active new regimen in patients
      with advanced carcinoma of the urothelium. A phase II trial of the Eastern
      Cooperative Oncology Group (E5892).
AB  - BACKGROUND: This study was conducted to assess the efficacy and toxicity of
      vinblastine, ifosfamide, and gallium nitrate (VIG) as first-line chemotherapy in
      patients with locally advanced or metastatic carcinoma of the urothelium.
      METHODS: Forty-five eligible patients were enrolled and stratified into good and
      poor risk groups. Poor risk was defined as age > or = 70 years, 1 functioning
      kidney, and prior adjuvant or neoadjuvant chemotherapy. Good risk patients were
      treated with vinblastine, 0.11 mg/kg, on Days 1 and 2; ifosfamide, 1.2 g/m2, on
      Days 1-5 with mesna uroprotection; and gallium nitrate, 300 mg/m2, as a
      continuous infusion on Days 1-5. Poor risk patients received similar therapy with
      doses decreased by 20% and administered over 4 days. All patients received
      recombinant human granulocyte-colony stimulating factor. Cycles were repeated at
      21-day intervals until disease progression or to a maximum of 6 cycles. RESULTS:
      Twenty of 45 patients (44%; 95% confidence interval, 30-60%) demonstrated an
      objective response, with 6 patients (13%) achieving a complete clinical response.
      The median duration of response was 47 weeks and the median survival duration for
      all patients was 10 months. Hematologic toxicity was significant, with 28
      patients and 31 patients experiencing Grade 3 or 4 leukopenia and anemia,
      respectively. Six patients had clinically significant cardiac events (primarily
      atrial arrhythmias). There were two early deaths that were possibly treatment
      related. CONCLUSIONS: VIG is an active regimen in patients with advanced
      urothelial carcinoma. Toxicity is significant but acceptable. Patients with
      significant cardiac disease (especially arrhythmias) should be treated with extra
      care. The 4-day regimen appears to have similar therapeutic efficacy with less
      toxicity.

PMID- 8988735
TI  - 18-Fluorodeoxyglucose uptake and survival of patients with suspected recurrent
      malignant glioma.
AB  - BACKGROUND: After intensive initial radiation therapy for malignant glioma,
      magnetic resonance imaging (MRI) and computerized tomography (CT) cannot
      distinguish tumor progression from radiation injury. METHODS: The authors studied
      the prognostic value of 18-fluorodeoxyglucose positron emission tomography (FDG
      PET) in 55 patients with malignant glioma for whom MRI obtained after initial
      surgery and radiation therapy demonstrated enlarging, enhancing lesions
      consistent with either tumor progression or radiation necrosis. Forty patients
      (73%) had an initial diagnosis of Grade 4 malignant glioma and 15 (27%) had Grade
      3 malignant glioma. The FDG-PET scans were graded visually on a four-level scale
      at the time of acquisition. RESULTS: In univariate analysis, the FDG-PET score
      was a significant predictor of survival time after FDG-PET scanning (P = 0.005).
      Median survival was 10 months for patients with FDG-PET scores of 2 or 3 (glucose
      uptake > or = adjacent cortex) and 20 months for those with scores of 0 or 1
      (glucose uptake < adjacent cortex). In multivariate proportional hazards
      analysis, the FDG-PET score was a significant predictor of survival (P = 0.019)
      in a model that included patient age, recurrence number, and FDG-PET score. There
      was no significant difference in the FDG-PET score hazard ratio for patients with
      Grade 3 or 4 tumors at initial diagnosis, first or later suspected recurrence,
      initial photon irradiation given with standard fractions or hyperfractionation,
      or stereotactic irradiation prior to FDG-PET scanning. CONCLUSIONS: This analysis
      demonstrates that FDG-PET scanning has prognostic value in a cohort limited to
      patients with suspected recurrent high grade glioma.

PMID- 8988736
TI  - Gangliogliomas in adults.
AB  - BACKGROUND: Gangliogliomas are rare tumors occurring in both children and adults
      that are characterized by the presence of neoplastic cells resembling both
      neurons and glia. METHODS: The authors reviewed 18 adults patients with
      intracranial gangliogliomas treated at the study institutions between October
      1987 and November 1995. RESULTS: The median age at diagnosis was 33.7 years, with
      a range of 21 to 55 years. Median follow-up was 37.7 months, with a range of 4
      months to 13 years. Clinical manifestations among the patients included seizures
      (13), headache (2), ataxia (1), and hemiparesis and paresthesias (1 patient
      each). Tumors were located in the temporal lobe (6 patients), temporal lobe and
      thalamus (1 patient), frontal lobe (5 patients), cerebellum (4 patients), and
      insula or thalamus (1 patient each). Thirteen patients underwent gross total
      resection, 4 underwent incomplete resection, and 1 underwent only a stereotactic
      biopsy. Treatment modalities included surgery only, surgery plus radiation, and
      surgery plus radiation and chemotherapy. Median survival was 90.3 months, with a
      range of 14 months to 13 years. Three patients were dead at follow-up with a mean
      survival of 32.3 months. These patients showed anaplastic features in their
      pathology at initial surgery or surgery for recurrence. CONCLUSIONS: In adults,
      gangliogliomas have a relatively favorable prognosis; however, the presence of
      anaplastic features predicts a worse outcome.

PMID- 8988737
TI  - Long-term follow-up of patients with medullary carcinoma of the thyroid.
AB  - BACKGROUND: All patients with medullary carcinoma of the thyroid (MCT) diagnosed
      in Sweden during 1959 through 1981 were identified. There were 113 males and 134
      females with a mean age of 51.6 years (range, 11-85 years). The cohort was
      followed with regard to survival to identify prognostic factors. The results 5
      and 10 years after diagnosis have been presented previously. METHODS: The purpose
      of this study was to examine to what extent those prognostic factors found in the
      authors' previous analyses remained independent prognostic factors for survival
      10 years or longer after diagnosis. The follow-up period was extended an
      additional 5 years and ranged between 11 and 32 years. RESULTS: The relative
      survival rate was 69.2% and 64.7%, respectively, 10 and 15 years after diagnosis.
      The survival rate was worse after excluding those patients with a family history
      of MCT (60.8% and 53.7%, respectively, 10 and 15 years after diagnosis). In
      multivariate analyses, age, tumor size, stage of the disease at diagnosis, tumor
      amyloid content and an euploid DNA pattern were found to be independent
      prognostic factors. However, in analyses of survival 10 years or longer after
      diagnosis only stage, tumor size, and age remained independent prognostic
      factors. CONCLUSIONS: There is still an excess mortality 10 years or longer after
      a diagnosis of MCT. However, the authors identified 3 groups of patients in whom
      the survival 10 years or longer after diagnosis did not differ from that of the
      general population: patients with a family history of MCT detected by screening,
      those with tumor size < 1 cm, or those with early stage disease at diagnosis.

PMID- 8988738
TI  - Increased expression of membrane type 1-matrix metalloproteinase in head and neck
      carcinoma.
AB  - BACKGROUND: Three types of membrane type-matrix metalloproteinases (MT-MMPs) have
      been identified as activators of pro-MMP2 (gelatinase A/72-kilodalton Type IV
      collagenase), which is believed to be crucial for tumor invasion and metastasis.
      MT1-MMP has been shown to be widely expressed in various tissues and to be
      overexpressed in lung and gastric carcinomas. METHODS: Activation of pro-MMP2 was
      examined in head and neck squamous cell carcinoma (HNSCC) by gelatin zymography.
      The expression of the MT1-MMP mRNA transcript was studied by Northern
      hybridization and that of MT1-MMP protein by immunohistochemical staining with a
      monoclonal antibody against MT1-MMP. RESULTS: Activation of pro-MMP2 was observed
      in ten of ten HNSCC tissues. Increased expression of the MT1-MMP mRNA transcript
      was also detected in eight of eight of these tissues. MT1-MMP positive cells were
      detected at the tumor cell lesions in the majority of these carcinoma tissues by
      immunohistochemical staining (24 of 27). MT1-MMP expression was more intense in
      moderately and well differentiated tumors than in poorly differentiated ones (P <
      0.05). CONCLUSIONS: These results suggest that MT1-MMP is involved in the
      activation of pro-MMP2 in HNSCC. These findings suggest that MT1-MMP is
      significant not only as a tumor marker but as a new target for chemotherapy
      against HNSCC.

PMID- 8988739
TI  - Definitive irradiation in the treatment of Hodgkin's disease. Analysis of
      outcome, prognostic factors, and long-term complications.
AB  - BACKGROUND: In the curative treatment of Hodgkin's disease, many institutions
      give doses above 40 Gray (Gy). To assess the effectiveness of treating patients
      with 35 Gy, data from a single institution regarding survival, prognostic
      factors, patterns of failure, and secondary complications were reviewed. METHODS:
      Data for a total of 172 patients with Hodgkin's disease were reviewed. All
      patients received definitive irradiation between 1971 and 1994. Median follow-up
      was 110 months. Kaplan-Meier methods were used to estimate survival, relapse-free
      survival, and complication rates. RESULTS: Relapse-free survival was 83% at 5
      years and 76% at 10 years. The only two prognostic factors related to relapse
      free survival were the stage of disease and the number of sites. The involved
      infield control rate was 96%. The 10-year estimates of hypothyroidism and second
      malignancies were 14% and 10%, respectively. CONCLUSIONS: Doses of 35 Gy are
      adequate for treating Hodgkin's disease. The stage of disease and the number of
      sites are predictive of relapse-free survival. The incidence of late
      complications necessitates long term surveillance of these patients.

PMID- 8988740
TI  - Recruiting cancer patients to participate in motivating their relatives to quit
      smoking. A cancer control study of the Cancer and Leukemia Group B (CALGB 9072).
AB  - BACKGROUND: A diagnosis of cancer provides a teachable moment in which a
      physician can counsel or teach the patient. The Cancer and Leukemia Group B
      hypothesized that this teachable moment could also be used to encourage
      counseling of the patients' relatives who smoke. The authors' first study sought
      to determine the feasibility of such an intervention, the cooperation of the
      patients, and the compliance of relatives who were smokers. The long-range goal
      is to recruit by mail a large population of adult smokers into an intervention
      program and to assist them in quitting cigarette smoking. METHODS: Oncologists
      and their clinical research associates asked recently diagnosed cancer patients
      to identify their relatives who were smokers and assist in persuading them to
      quit. Consenting patients spoke to relatives and mailed them a personalized
      motivational leaflet along with a list of the benefits of quitting smoking.
      Intervention was continued only with relatives who were contacted in this manner.
      The participating physicians then wrote to the smokers, advising them to quit;
      enclosed with each physician's letter were the National Cancer Institute booklet
      "Clearing the Air," which is about quitting smoking, and a questionnaire
      determining "stage of change" (the stage of the smoker's inaction or action
      regarding quitting smoking). After 6 months, a postintervention questionnaire was
      mailed to the relatives. RESULTS: Written consent was obtained from 89% of 144
      eligible patients solicited. Eighty percent of patients involved in the study
      contacted relatives. Sixty-three percent of contacted relatives returned the
      first questionnaire and 40% answered the second. Nine percent of all contacted
      relatives reported having quit smoking after the intervention. CONCLUSIONS: The
      intervention proved to be feasible and will lead to the next study, which will
      randomize relatives who smoke within a more intensive intervention over 12 months
      and compare the results with nonintervention controls.

PMID- 8988741
TI  - Long-term survival of patients with recurrent or refractory germ cell tumors
      after high dose chemotherapy.
AB  - BACKGROUND: The optimal treatment of patients with recurrent or refractory germ
      cell tumors is still a debated topic. High dose chemotherapy (HDCT) with
      autologous stem cell rescue (ASCR) might be promising for intensification of
      first or subsequent salvage treatment. However, the long-term results of this
      approach remain largely unknown. METHODS: Between August 1989 and September 1992,
      74 patients with recurrent and/or refractory germ cell tumors were treated in a
      Phase I/II trial with HDCT consisting of carboplatin (1500-2000 mg/m2), etoposide
      (1200-2400 mg/m2), and ifosfamide (0-10 g/m2). In September 1995 all patients
      were reevaluated to determine overall response, late toxicities, and survival.
      RESULTS: Two patients died from treatment-related toxicity shortly after HDCT,
      and 47 had recurrence or progression of disease after a median of 3 months
      (range, 1-44 months). Of these latter patients, three were living continuously
      disease free at the conclusion of this study after a second HDCT regimen, salvage
      surgery, or chronic oral etoposide treatment. The results were an overall
      survival of 38% (95% confidence interval, 27-50%) and a failure free survival of
      31% (95% confidence interval, 21-43%) at 5 years. There were no long-term
      survivors among patients whose disease progressed while they were receiving
      conventional doses of cisplatin before HDCT. Late toxicities consisted mainly or
      renal impairment (in 21% of patients), paresthesias (in 29%), and ototoxicity (in
      18%). CONCLUSIONS: HDCT can be curative for patients with germ cell tumors who do
      not become disease free after conventional dose chemotherapy but respond to this
      treatment.

PMID- 8988742
TI  - Dienogest, a novel synthetic steroid, overcomes hormone-dependent cancer in a
      different manner than progestins.
AB  - BACKGROUND: Dienogest is a synthetic progestational steroid that is used for
      contraception. It is being studied for the treatment of endometriosis, but its
      anticancer activity remains unknown. The authors investigated the anticancer
      effect of dienogest on hormone-dependent cancers. METHODS: The authors used two
      cell lines derived from human endometrial carcinoma (HEC-88nu cells expressing
      estrogen receptors [ER] but not progesterone receptors [PR] and Ishikawa cells
      expressing both ER and PR) and a cell line derived from human breast carcinoma
      (MCF-7 cells expressing both ER and PR). The authors examined the in vivo
      antitumor activity and the antiuterotropic activity of dienogest in mice and
      compared it with the activity of several progestins. RESULTS: At oral doses of
      0.01-1 mg/kg/day, dienogest significantly suppressed the 17 beta-estradiol
      benzoate (E2)-dependent tumor growth of HEC-88nu cells, which were unresponsive
      to known progestins such as medroxyprogesterone acetate (MPA, 100 mg/kg/day,
      administered orally) and norethisterone (NES, 100 mg/kg/ day, administered
      orally). The suppressive effect of dienogest on tumor growth was not diminished
      in the presence of excess MPA. Dienogest also suppressed the E2-dependent tumor
      growth of both Ishikawa and MCF-7 cells, both of which responded to MPA. However,
      the minimum effective dose of dienogest (0.01-1 mg/kg/day) was much lower than
      that of MPA (100 mg/kg/day). In contrast, dienogest did not suppress the E2
      induced increase in uterine weight, whereas MPA and NES suppressed it
      significantly. CONCLUSIONS: Dienogest showed potent anticancer activity against
      hormone-dependent cancers at doses at which progestins show no activity.

PMID- 8988743
TI  - Metabolic changes in elderly cancer patients after glucose ingestion. The role of
      tumor necrosis factor-alpha.
AB  - BACKGROUND: Previous studies have demonstrated an increased basal metabolic rate
      in cancer patients. However, no previous study has investigated the changes in
      energy expenditure and substrate oxidation after administration of a glucose
      load. Furthermore, the role of tumor necrosis factor-alpha (TNF-alpha) on cancer
      induced metabolic changes is still a neglected area. METHODS: In 25 cancer
      patients and 16 healthy subjects matched with regard to age, body mass index, and
      fat-free mass, indirect calorimetry was made before and after administration of a
      glucose load (75 g per subject, administered orally). RESULTS: Cancer patients
      had fasting plasma concentrations of insulin (74 +/- 3.3 vs. 67 +/- 4.1 pmol/L; P
      < 0.05), lactate (0.68 +/- 0.11 vs. 0.41 +/- 0.1 mmol/L; P < 0.05), free fatty
      acids (884 +/- 121 vs. 342 +/- 76 mmol/mL; P < 0.001), and TNF-alpha (1.23 +/-
      0.31 vs. 0.45 +/- 0.11 ng/mL; P < 0.01) greater than controls, whereas plasma
      glucose concentrations (4.8 +/- 0.5 vs. 5.1 +/- 0.3 mmol/L; P = not significant)
      were not different from controls. Indirect calorimetry at baseline demonstrated
      that basal metabolic rate, fat oxidation, and protein oxidation were
      significantly greater in cancer patients than in controls. After administration
      of the glucose load, carbohydrate oxidation progressively rose in both cancer
      patients and controls, with no differences between the two groups, whereas
      glucose uptake (59.3 +/- 3.8 vs.69.1 +/- 3.6 g/kg fat-free mass [FFM] x 240
      minutes; P < 0.01) and storage (49.1 +/- 4.1 vs. 60.2 +/- 3.3 g/kg FFM x 240
      minutes; P < 0.05) were markedly reduced in cancer patients as compared with
      controls. Finally, glucose-induced thermogenesis (GIT) was lower in cancer
      patients than in controls. CONCLUSIONS: This study demonstrated that GIT is lower
      in cancer patients than in healthy subjects matched with regard to age and body
      mass index. An overactivity of the glucose fatty acid cycle is responsible for
      such results. Plasma concentrations of TNF-alpha might play a modulating role in
      the metabolic changes that occur after administration of a glucose load. The role
      of TNF-alpha on glucose and lipid metabolism in cancer patients would be a worthy
      subject of future investigations.

PMID- 8988744
TI  - Predictors of survival in patients with carcinoma of the gallbladder.

PMID- 8988745
TI  - Thermography. Its relation to pathologic characteristics, vascularity,
      proliferation rate, and survival of patients with invasive ductal carcinoma of
      the breast.

PMID- 8988746
TI  - The fall in incidence of prostate carcinoma. On the down side of a prostate
      specific antigen induced peak in incidence--data from the Utah Cancer Registry.

PMID- 8988747
TI  - Prospective randomized clinical trial to evaluate the optimal dose of 131I for
      remnant ablation in patients with differentiated thyroid carcinoma.

PMID- 8988748
TI  - Pregnancy-associated lymphomas. A clinicopathologic study.

PMID- 8988749
TI  - Post-irradiation malignant mesothelioma.

PMID- 8988750
TI  - 9th Congress of the European College of Neuropsychopharmacology. Amsterdam, The
      Netherlands, September 21-25, 1996. Abstracts.

PMID- 8988751
TI  - 27th annual meeting of the Deutsche Gesellschaft fur Immunologie. Hamberg,
      September 26-28, 1996. Abstracts.

PMID- 8988752
TI  - FDI/ADA Orlando Congress abstracts.

PMID- 8988755
TI  - British Human Genetics Conference 1996. University of York, September 16-18,
      1996. Abstracts.

PMID- 8988754
TI  - 14th World Congress on Endourology and SWL 12th Basic Research Symposium.
      Melbourne, Australia, November 11-14, 1996. Abstracts.

PMID- 8988753
TI  - 6th World Congress for Microcirculation. Munich, Germany, August 25-30, 1996.
      Abstracts.

PMID- 8988756
TI  - Monovalent latex agglutination reagents for the diagnosis of nonmeningitic
      pneumococcal infection.
AB  - The pneumococcus is a leading cause of serious bacterial infection worldwide.
      Given the difficulties with available assays for the diagnosis of invasive
      nonmeningitic pneumococcal infection, we evaluated monovalent slide latex
      agglutination reagents among patients with blood culture-confirmed pneumococcal
      infection and control patients in Baltimore, Maryland, USA; Sao Paulo, Brazil;
      and Cairo, Egypt. Among 50 patients with invasive nonmeningitic pneumococcal
      infection, 23 had a positive urine test for a sensitivity of 46% (95% confidence
      intervals of 32% and 61%). Among 39 healthy children, 36 had a negative assay,
      for a specificity of 92% (95% confidence intervals of 78% and 98%). Among 80
      children with pneumonia without a positive blood culture for Streptococcus
      pneumoniae, the specificity was 88% (95% confidence intervals of 78% and 94%).
      Although the assay was fairly specific, the positive predictive value using
      optimistic assumptions was only 73%-83%. This study suggests that this assay has
      a sensitivity and positive predictive value that may limit its value in some
      settings.

PMID- 8988757
TI  - Diagnosis of Legionella pneumophila, Mycoplasma pneumoniae, or Chlamydia
      pneumoniae lower respiratory infection using the polymerase chain reaction on a
      single throat swab specimen.
AB  - Diagnosis of Mycoplasma pneumoniae and Chlamydia pneumoniae lower respiratory
      infections using DNA amplification by polymerase chain reaction (PCR) on throat
      swab specimens has been reported. In this study we determined the sensitivity of
      the detection of Legionella pneumophila in simulated throat swab specimens by
      PCR. Next, we compared the sensitivity and specificity of a single throat swab
      PCR with the current tests for diagnosis of Legionella spp., M. pneumoniae, and
      C. pneumoniae in patients with lower respiratory tract infections. Patients' work
      up included: (a) throat swab specimen for Legionella spp., M. pneumoniae, and C.
      pneumoniae PCR; (b) throat swab specimen for C. pneumoniae culture; (c) sputum
      specimen for L. pneumophila direct fluorescent antibody and culture; (d) urine
      specimen for L. pneumophila serogroup 1 antigen detection; and (e) serum specimen
      for L. pneumophila, M. pneumoniae, and C. pneumoniae acute and convalescent
      antibody titers. A total of 155 patients with lower respiratory infection were
      enrolled in this prospective study. Throat swab PCR was positive for Legionella
      spp. in five of the six patients with legionellosis, indicating the presence of
      this organism in the oropharynx of patients with Legionnaires disease. Mycoplasma
      pneumoniae PCR was positive in eight of the nine patients with mycoplasma
      infection. Chlamydia pneumoniae PCR was positive in the two patients with C.
      pneumoniae infection. None of the other 138 patients with negative PCR had other
      positive confirmatory tests for respiratory infection by these three organisms
      (100% specificity). PCR was able to detect 15 of the 17 infected (88.2%). Results
      of this investigation indicate that PCR on a single throat swab specimen is a
      rapid, sensitive, and specific test that may greatly simplify the diagnosis of
      lower respiratory infection caused by Legionella spp., Mycoplasma pneumoniae, or
      C. pneumoniae.

PMID- 8988758
TI  - Application of the Roche Amplicor Mycobacterium tuberculosis (PCR) test to
      specimens other than respiratory secretions.
AB  - The ability of the Roche AMPLICOR Mycobacterium tuberculosis (MTB) test to detect
      M. tuberculosis in specimens other than respiratory secretions was evaluated. A
      total of 249 specimens from 219 patients were tested. Of these, 12 specimens grew
      isolates of the M. tuberculosis complex and four grew isolates of the M. avium
      complex. The AMPLICOR MTB test was positive for 10 of the 12 specimens which grew
      M. tuberculosis and for three specimens which were culture negative. Two of the
      latter specimens were from patients with a clinical diagnosis of tuberculosis and
      with multiple sputum specimens which grew M. tuberculosis. Four specimens grew M.
      avium complex isolates, and all yielded negative AMPLICOR MTB test results. The
      sensitivity, specificity, and positive and negative predictive values for the
      AMPLICOR MTB test were 85.7%, 99.5%, 92.3%, and 99.1%, respectively. Our data
      indicate that the AMPLICOR MTB test will permit the rapid detection of M.
      tuberculosis in specimens other than respiratory secretions.

PMID- 8988759
TI  - Association of quantitative cytomegalovirus antigenemia with symptomatic
      infection in solid organ transplant patients.
AB  - A prospective virologic follow-up of solid organ transplant patients was designed
      to determine the usefulness of antigenemia and viremia as virologic markers for
      the diagnosis of cytomegalovirus (CMV) infections, and also for monitoring CMV
      disease and therapy control. A total of 629 blood samples from 127 patients (60
      liver, 47 kidney, and 20 heart transplant recipients) were studied by tube and
      shell vial cultures, and by antigenemia assay. This later was carried out by an
      indirect immunofluorescent assay method for formalin-fixed cytospin slides
      containing 2 x 10(5) leukocytes, using a monoclonal antibody directed against the
      CMV pp65 antigen. CMV was detected by at least one of the three methods in 238
      specimens (37.8%) from a total of 63 patients. The antigenemia assay was positive
      in 215 (90.3% of positive samples). A total of 94 samples were detected only by
      this marker, which occurred either in samples with low positive counts (70.2%
      with antigenemia counts < 10 positive cells/10(5) leukocytes) or in specimens
      from treated patients. There were 30 episodes of CMV disease in 23 patients.
      Antigenemia was positive in all these episodes, 27 of them with counts > 20
      positive cells/10(5) leukocytes. With this cut-off, positive and negative
      predictive values for symptomatic CMV infection were 100% and 97.2%,
      respectively. The antigenemia assay is a rapid, sensitive, specific, and early
      marker of CMV infection in transplantees. Cultures became negative with antiviral
      therapy while remaining antigenemia detectable. There was an association between
      highest quantitative antigenemia test results and clinical symptoms in our
      patients. In its quantitative version, the assay is useful to detect symptomatic
      infection and appears to be a helpful tool in managing patients at risk and in
      guiding antiviral therapy.

PMID- 8988760
TI  - Evaluation of rapid culture centrifugation method for adenovirus detection in
      stools.
AB  - Routine laboratory testing for adenovirus (Adv) requires a procedure that is
      rapid and reliable, especially for samples from children and immunosuppressed
      patients, when diarrhea may signal the onset of severe gastrointestinal
      disorders. An improved culture technique for Adv isolation, using centrifugation
      step of 24-well plates and needing only 48 h incubation, was evaluated for 382
      stool samples. This technique was compared with conventional tube cell culture
      and a commercial enzyme-linked immunosorbent assay (ELISA) kit. Adv was isolated
      in 36 samples (9.4%) by rapid culture, in 32 (8.4%) by conventional culture, and
      in 42 samples (11%) using genus-specific ELISA. A total of 30 isolates were found
      to be Adv positive in both rapid and conventional cultures, and half of the Adv
      positive rapid culture isolates were identified as serotypes 40/41 using a type
      specific ELISA. The improved culture method considerably reduces incubation time
      and also offers a slightly enhanced sensitivity to Adv serotypes. Combined with
      appropriate cell lines adapted to the isolation of enteric adenoviruses, it
      therefore constitutes a valuable laboratory test particularly useful in the
      diagnosis of gastroenteritis.

PMID- 8988761
TI  - Comparison of the Murex Candida albicans CA50 test with germ tube production for
      identification of C. albicans.
AB  - A total of 502 yeast isolates were tested with the 30-min MUREX Candida albicans
      CA50 (Norcross, GA) test for presumptive identification of C. albicans. The
      results were compared with the standard 2-h germ tube test, which was the
      reference standard. Of the 502 isolates, 316 were C. albicans and 186 were non-C.
      albicans. Identifications were based on germ tube reactions; the API20C and
      chlamydospore agars were used when discrepant results persisted between the germ
      tube and MUREX test after repeat testing of the MUREX method. A total of 16 C.
      albicans gave negative results on initial testing with the MUREX test but were
      interpreted as positive when repeated. Three germ tube negative yeasts initially
      tested positive with the MUREX but were negative when repeated. Two additional
      yeast isolates gave incorrect results with the MUREX, even with repeat testing:
      C. albicans and C. lusitaniae. The initial sensitivity and specificity for the
      MUREX C. albicans CA50 test were 94.6% and 97.8%, respectively. As an addition to
      the study, two fetal bovine sera were compared for production of germ tubes;
      fetal bovine serum and Fetal Clone II. The testing found them to be in 100%
      agreement.

PMID- 8988762
TI  - Antimicrobial susceptibility testing of Helicobacter pylori. Comparison of E
      test, broth microdilution, and disk diffusion for ampicillin, clarithromycin, and
      metronidazole.
AB  - The optimal method for the determination of the minimum inhibitory concentration
      (MIC) of antimicrobials against Helicobacter pylori has not been established. The
      epsilometer agar diffusion gradient test (E-Test; AB Biodisk, Solna, Sweden) was
      compared with broth microdilution, the reference method, and disk diffusion for
      the antimicrobial susceptibility testing of 122 clinical isolates of H. pylori to
      ampicillin, clarithromycin, and metronidazole. Isolates were considered to be
      resistant when the MIC values was > 8 micrograms/ml for either ampicillin or
      metronidazole and > 2 micrograms/ml for clarithromycin. For an individual
      isolate, the MICs for ampicillin and clarithromycin determined by broth
      microdilution and the E-test were highly reproducible, with replicate results
      being within +/- 1 log2 dilution. The correlation between the MICs determined by
      E-test and broth microdilution was excellent for both ampicillin and
      clarithromycin (90.1% and 88.5% were within +/- log2 dilution, and 98.3% and
      96.7% of the values were within +/- 2 log2 dilution, respectively). In no
      instance did the interpretation of "sensitive" or "resistant" differ. Conversely,
      only 70.5% of the E-test results of metronidazole were within +/- 1 log2 dilution
      of the broth microdilution results. In addition, 15 (12.3%) of the H. pylori
      isolates interpreted as resistant by the E-test were sensitive by the broth
      microdilution method. All discrepancies occurred when the E-test MIC values fell
      between 8 and 32 micrograms/ml. The results of the ampicillin and clarithromycin
      disk diffusion assay correlated 100% with the results of the broth microdilution.
      However, these data suggest that when the E-test MIC results of metronidazole
      yield values between 8 and 32 micrograms/ml, the MIC should be reevaluated by
      another method.

PMID- 8988763
TI  - Bacteremia due to Agrobacterium tumefaciens (radiobacter). Report of infection in
      a pregnant women and her stillborn fetus.
AB  - Agrobacterium tumefaciens (radiobacter) is usually a plant pathogen, but is
      isolated occasionally from human clinical specimens, frequently along with other
      bacteria. Agrobacterium tumefaciens (radiobacter) has been isolated from blood,
      central intravenous catheters, peritoneal fluid, urine, and cellulitis aspirates,
      often in immunocompromised individuals. This report details the isolation of A.
      tumefaciens (radiobacter) from the blood of a pregnant woman, as well as from the
      blood of her stillborn, premature fetus. It is, to our knowledge, the first
      report of such an occurrence.

PMID- 8988764
TI  - Adrenal insufficiency, recurrent bacteremia, and disseminated abscesses caused by
      Nocardia asteroides in a patient with acquired immunodeficiency syndrome.
AB  - Nocardia asteroides is an opportunistic pathogen of increasing incidence in human
      immunodeficiency virus (HIV)-infected persons. The lungs are the most common site
      of infection, followed by the brain; involvement of other extrapulmonary sites is
      less common. We describe a patient with acquired immunodeficiency syndrome who
      presented with a number of unique manifestations of nocardial infection: the
      first reported case of bilateral adrenal abscesses with adrenal insufficiency,
      the first case of a renal abscess due to N. asteroides alone, and the first case
      of recurrent, symptomatic bacteremia. A review of the literature on nocardial
      infections in HIV-positive individuals is presented.

PMID- 8988765
TI  - Two investigational glycylcyclines, DMG-DMDOT and DMG-MINO. Antimicrobial
      activity studies against gram-positive species.
AB  - DMG-DMDOT (CL-331,002 OR CL-331,928) and DMG-MINO (CL-329,998 or CL-344,677) are
      two new semisynthetic tetracyclines called glycylcyclines, with a broad spectrum
      of activity and includes Enterobacteriaceae, Gram-positive cocci, JK
      diphtheroids, and Bacillus cereus. Potent activity was demonstrated against all
      Streptococcus spp. strains [minimum inhibitory concentrations] (MIC90S) 0.06-0.25
      micrograms/ml) and staphylococci (oxacillin susceptible ans resistant; MIC90S
      0.12-2 micrograms/ml). Both glycylcyclines (MIC90, 0.06 micrograms/ml) were more
      potent than minocycline (MIC90 8 micrograms/ml) against Enterococcus faecium,
      many of which were vancomycin resistant (116 strains). Organisms with minocycline
      MICs at > or = 8 micrograms/ml (Staphylococcus aureus, enterococci, beta
      hemolytic streptococci, and pneumococci) had glycylcycline MIC results ranging
      from 0.06 to 0.5 micrograms/ml (e.g., apparent use against existing tetracycline
      resistance phenotypes). Drugs in this class appear promising for therapy of
      infections caused by Gram-positive species now testing resistant to contemporary
      antimicrobial agents, and further development of compounds in this class is
      encouraged.

PMID- 8988766
TI  - Activity of the quinupristin-dalfopristin combination (RP-59500; Synercid) tested
      against vancomycin-resistant Enterococcus species.

PMID- 8988767
TI  - The use of the labiocolumellar crease incision in rhinoplasty.
AB  - Aurel Rethi, in 1934, first described the transverse upper columellar incision
      for open rhinoplasty for resection of a portion of columella in cases of overly
      projecting nasal tip. The mid columellar incision has come to be known as the
      "Rethi" incision. Numerous variations of this approach have been popularized
      through the years. Recently, a great debate has raged over the criteria to be
      used in selecting patients for rhinoplasty. In this paper, we review 100
      consecutive rhinoplasties and discuss our technique of labiocolumellar crease
      incision for open approach, and relate the criteria that we utilize to select
      patients for open rhinoplasty. There were 37 male and 63 female patients. Of
      these, 32 primary, 45 secondary, 18 cleft, and 5 reconstructive rhinoplasties
      were performed. Twenty-eight percent of primary, 62% of secondary, 78% of cleft,
      and 80% of reconstructive rhinoplasties were performed using the open approach
      via the labiocolumellar crease incision. There were no cases of circulatory
      compromise of the columella. The presence of a scar along the columella base (as
      with the C-flap in cleft patients) should be an indication for open rhinoplasty.
      Several myths about the labiocolumellar crease incision are dispelled. Adhering
      to principles of aesthetic subunits should guide the surgeon to place scars in a
      less noticeable position.

PMID- 8988768
TI  - Transblepharoplasty forehead lift and upper face rejuvenation.
AB  - A complete upper face rejuvenation via blepharoplasty incisions is feasible. This
      technique is indicated in: (1) patients with male pattern baldness, (2) patients
      with a history of hair transplants, (3) patients with excessively high foreheads,
      (4) patients in which upper blepharoplasty is planned simultaneously with the
      brow lift, (5) patients with spastic frontalis syndrome, and (6) patients needing
      periorbital or bicularis muscle repositioning. Standard upper blepharoplasty
      incisions are made. Dissection is proceeded to the superior orbital rim. All the
      soft tissues, including the retro-orbicularis oculi fat (ROOF) pad, are elevated.
      A cuff of periosteum and the overlying subgaleal fascia is left. Superior
      dissection in the frontal area can proceed subgaleally or sub-periosteally. In
      the latter case, the periosteum is entered about 1.5 cm above the orbital rim. In
      the temporal area, dissection is done in the subgaleal plane up to 1 cm above the
      zygomatic arch. This dissection is accurately and safely done with the aid of the
      endoscope introduced through the same incision. Resection of the procerus and
      corrugator muscles is performed via the eyelid incision, identifying and
      protecting the supratrochlear and supraorbital nerves. Extra-fine-tip cautery is
      used for hemostasis. Initial fixation consists of suturing the ROOF pad to the
      periosteum of the orbital rim (two sutures). The tail of the brow is sutured to
      the temporal fascia (third suture). The frontotemporal flap can be stabilized in
      an elevated position with an external tied-over dressing, percutaneous screws, or
      well-supportive contouring tape, depending on the clinical situation. The eyelids
      are closed in a standard fashion. This operation was performed on 14 patients--12
      with the assistance of the endoscope and in 2 without the endoscope. However, the
      endoscope has made the operation more precise. Analysis of the brow position,
      frontalis and corrugator activity, and the aesthetics of the upper face reveal
      that this operation can give results similar to other techniques with comparable
      morbidity, more expeditiously and with fewer scars.

PMID- 8988769
TI  - Reduction mammaplasty: the results of avoiding nipple-areolar amputation in cases
      of extreme hypertrophy.
AB  - In extreme cases of breast hypertrophy, amputation of the nipple-areolar complex
      and transplantation during reduction mammaplasty has been advocated to avoid
      nipple necrosis. We report our experience with 172 patients having inferior
      breast pedicle reduction without amputation of the nipple-areolar complex. Mean
      total weight of resected tissue was 1,946 g (548 to 5,100 g), with a mean nipple
      areolar transposition of 10 cm (0.5 to 23 cm). Dividing patients into four groups
      by weight of resection, we compared complication rates. In this series, where
      nipple-areola amputation was avoided, there was a 99.6% survival rate of the
      nipple-areolar complex with 97.1% retention of nipple sensibility. Patients with
      extreme breast hypertrophy (3,000 g resected tissue) experienced no increase in
      complications when compared to smaller reductions. In most cases of
      gigantomastia, amputation of the nipple can be avoided using the inferior breast
      pedicle technique. Size of breast resection alone should not determine the fate
      of the nipple.

PMID- 8988770
TI  - Silicon tissue assay: are there intracapsular variations?
AB  - In previous studies, we were able to demonstrate baseline non-augmented cadaveric
      silicon tissue values as well as silicone-augmented breast capsular tissue
      silicon levels from various geographic locations in the United States. One of the
      limitations of these previous studies was the potential for intracapsular
      variations in the silicon level and whether a single measurement would be a valid
      comparison for the entire breast capsule. This study was then undertaken to
      measure the variations in tissue silicon levels from multiple sites within each
      breast capsule sampled. Four patients that underwent silicone breast and three
      tissue expander explantations were evaluated. All the women had silicone implants
      for breast augmentation and the placement of tissue expanders for reconstruction
      following mastectomy. A variety of reasons for explantation were noted. Each of
      the patient's breast capsules were divided into four quadrants (upper inner,
      upper outer, lower inner, and lower outer). All samples were harvested in a no
      touch technique and were sent for silicon tissue assays. Silicon values ranged
      from 44 to 9,000 micrograms per gram of tissue and were consistent with our
      previously measured values. We conclude that random samples of breast capsules
      reflect the variations within the specimen samples, but can be used to measure
      elevated silicon values accurately. It is our belief that multiple samples do not
      need to be taken for each capsule measurement and that a previous potential
      limitation to the measurements has been eliminated.

PMID- 8988771
TI  - Free colon transfer: a versatile method for reconstruction of pharyngoesophageal
      defects with a large pharyngostoma.
AB  - Free transverse colon transfers based on the middle colic vessels were used to
      reconstruct a pharyngoesophageal defect in 9 patients. In all patients, cancer
      invaded up to the oropharynx. Resection resulted in a larger pharyngostoma than
      normally seen following standard total pharyngolaryngoesophagectomy. In such
      cases, it can be difficult to achieve good swallowing function after
      reconstruction using the free jejunal transfer. This mainly results from a
      significant discrepancy between the diameter of the pharyngostoma and that of the
      jejunum. Compared to the jejunum, the transverse colon has a larger diameter with
      a longer vascular pedicle and can provide a longer, straight intestinal tube,
      facilitating easy passage of a food bolus. In our series, all transfers survived
      well and all patients had good swallowing function postoperatively. We consider
      that a free colon transfer is more suitable than a free jejunal transfer for
      pharyngoesophageal reconstruction in patients with a large pharyngostoma.

PMID- 8988772
TI  - Effect of vascular endothelial growth factor (VEGF) on survival of random
      extension of axial pattern skin flaps in the rat.
AB  - Current evidence suggests that neovascularization is mediated by a wide range of
      angiogenic growth factors. Vascular endothelial growth factor (VEGF) appears to
      be one of the most important angiogenic factors in vivo. The aim of this project
      was to evaluate the efficacy of VEGF in augmentation of blood supply to skin
      flaps. Epigastric skin flaps were raised in 16 Sprague-Dawley male rats. In group
      A (N = 8), 5 micrograms of VEGF was injected into the epigastric artery after
      flap elevation. In the control, group B (N = 8), the artery was injected with
      saline. On the seventh day, the rats were photographed and the digital images
      were analyzed using imaging software (Image-Pro Plus 1.2). The blood flow in the
      flaps was measured with a percutaneous laser Doppler probe at specific locations.
      Histological studies of the flaps were done. Results showed that the mean
      percentage surviving flap area was 71.9% in group A and 53.7% in the control
      group, which is statistically significant (p < 0.001). Histological examination
      revealed increased density of the capillaries in the flaps treated with VEGF when
      compared to the control group. We believe the increase in skin survival is due to
      angiogenesis induced by the VEGF.

PMID- 8988773
TI  - Hypospadias repair: the influence of postoperative care and a patient factor on
      surgical morbidity.
AB  - More than 200 surgical techniques have been advocated for hypospadias repair and
      perfection is still eluding us. The purpose of this paper is not to comment on a
      surgical technique, but to highlight the importance of postoperative care on the
      eventual surgical outcome. Two hundred six children undergoing primary
      hypospadias surgery from 1984 to 1994 at Mount Vernon Hospital were analyzed. The
      mean age of surgery was 3.8 years (range, 8 months-17 years) and our mean follow
      up was 6.1 years. Various surgical techniques were used. During 1989, we changed
      our postoperative regime and patients were mobilized early (within 48 hours)
      compared to the strict-bed rest-till-catheter-out regime before 1988. This
      significantly reduced our fistula rate from 22% to 9.8% (chi squared p = 0.0016).
      Patient factors such as pulling on the catheter, urinary obstruction/blocked
      catheter, erections, straining due to constipation, and interference with
      dressings influence surgical outcome negatively. One of these patient factors was
      documented in all of our 33 patients who developed fistulas. In 6 patients
      (3.5%), a patient factor was present without any complication. This is highly
      significant statistically (chi squared p < 0.0001). The type of urinary
      diversion, period of urinary diversion, type of dressing, catheter size, and
      anesthetic regime did not influence outcome significantly.

PMID- 8988775
TI  - Distraction lengthening following growth cessation due to thumb replantation in a
      child.
AB  - Growth disturbance due to premature physeal closure as a sequela of digit
      replantation, on occasion, can cause shortening, resulting in suboptimal
      function. A simple method for correction using only local tissues is possible via
      gradual bony distraction. This was attempted in a toddler, whose dominant thumb
      was amputated by a riding lawn mower when he was an infant, because replantation
      caused significant growth cessation. The first metacarpal distraction over 64
      days netted 22 mm of lengthening. Because a further immobilization period to
      allow spontaneous consolidation by neo-osteogenesis was aborted at the family's
      insistence, a fibular autograft of that dimension was inserted into the created
      bony gap. Ultimately, after 24 months of follow-up, the distracted thumb had been
      increased 26% in length and was 88% of the length of the contralateral thumb at
      that time, compared to only 74% prior to initiating the distraction.

PMID- 8988774
TI  - Orbital hemorrhage during rhinoplasty.
AB  - The most common complication of rhinoplasty is perioperative and postoperative
      hemorrhage. We present two patients who experienced intraoperative orbital
      hemorrhage during rhinoplasty. Patients with a history of previous nasal trauma,
      because of scarring/altered anatomy, may be more prone to this serious
      complication. A precise and well-placed osteotomy must be done to avoid aberrant
      anatomy and complications. The proposed mechanism for orbital hemorrhage is
      shearing or tearing of fibrovascular scar tissue involving the angular vessels
      during the surgical dissection. Prompt recognition and management of an orbital
      hemorrhage during or following rhinoplasty is necessary to prevent possible
      ocular injury and loss of vision. A management algorithm for orbital hemorrhage
      is presented along with a discussion of surgical techniques to prevent this
      complication. Surgeons performing rhinoplasty should be cognizant of this type of
      intraoperative complication along with its medical and surgical management.

PMID- 8988776
TI  - Preexpanded radial forearm free flap to the scalp.
AB  - The radial forearm flap is a versatile tool for the reconstructive surgeon
      because of its thinness, durable skin quality, aesthetic match, and relative ease
      of dissection. This flap is an ideal candidate for reconstruction of head and
      neck defects. One of the drawbacks is its relative small size, which may limit
      its use in certain applications. We describe the preexpansion of the radial
      forearm flap for its use in covering a large scalp defect. Preexpansion of the
      radial forearm free flap enables the reconstructive surgeon to increase the size
      of the flap markedly without altering its neurovascular anatomic relationships.
      Also described is the unexpected benefit of a periprosthetic capsule that covers
      the flexor tendons of the forearm and acts as an excellent bed for a skin graft.

PMID- 8988777
TI  - Nasal dysplasia.
AB  - We report a case of a rare congenital nasal malformation. A young male patient
      was seen with a unilateral duplication of the left nostril. According to the
      morphogenetic classification, described by van der Meulen, this nasal
      malformation could be classified as a type IV nasal dysplasia. The other observed
      abnormalities that were seen were part of the CHARGE association, which is
      defined as coloboma of the iris, heart deformities, choanal atresia, retarded
      growth, genital and ear deformities. The patient underwent a surgical correction
      of the nose using an L-approach, yielding a satisfactory result 1 year
      postoperatively. Details of the case and a review of the scarce literature are
      presented.

PMID- 8988778
TI  - A case report on spontaneous return of levator function following postcataract
      blepharoptosis repair.
AB  - Blepharoptosis is a recognized complication of cataract extraction and other
      ocular procedures. A 6-month waiting period is recommended before repairing
      postcataract ptosis because most cases resolve during this time. We report the
      course of a patient who developed spontaneous recovery of eyelid function 11
      months after cataract surgery. She had previously undergone successful ptosis
      repair 8 months after cataract extraction, but developed overcorrection 3 months
      later as her levator function returned to normal. We recommend at least a 1-year
      waiting period before repair of postcataract ptosis. If corrective surgery is
      undertaken earlier than 1 year due to visual obstruction or for aesthetic
      reasons, we suggest two guidelines. The levator should be plicated rather than
      resected and patients should be forewarned of the possibility for a revisionary
      procedure if spontaneous return of levator function occurs.

PMID- 8988779
TI  - Spontaneous esophageal perforation in an acute burn patient.
AB  - Spontaneous perforation of the esophagus is an uncommon and catastrophic event
      accompanied by extremely high morbidity and mortality. In a burn patient,
      diagnosis may be delayed because of painful burns that may mask the underlying
      problem. Diagnosis is dependent on a high index of suspicion and by inclusion of
      this entity in the differential diagnosis of chest pain. The authors report on a
      45-year-old male who developed a spontaneous perforation of the esophagus while
      hospitalized for treatment of an 11% total body surface area burn. Diagnosis and
      initiation of appropriate treatment resulted in salvage of this patient. The
      pathophysiology of this disease and a review of the literature are presented.

PMID- 8988780
TI  - Gluteal infarction as a complication of aortofemoral bypass grafting.
AB  - Early complications following aortofemoral bypass grafting include acute limb
      ischemia, renal failure, bowel and spinal cord ischemia, and myocardial
      infarction. Although the literature recognizes these more common complications,
      we have found very few reports that raised the possibility of an anatomically
      determined, soft-tissue infarction as a complication of aortofemoral bypass
      grafting. Our plastic surgery service was consulted in August and October 1992 to
      examine 2 patients with soft-tissue complications following aortofemoral bypass
      grafting. Both patients were found to have complete gluteal infarction.
      Recognition of muscle infarction following aortofemoral grafting must be
      distinguished from postoperative pressure sores, since the muscle infarction
      requires prompt and thorough anatomic debridement to prevent in situ muscle
      liquefaction and sepsis.

PMID- 8988781
TI  - Pseudoaneurysm of the anterior superficial temporal artery.
AB  - Pseudoaneurysm of the superficial temporal artery must be considered in the
      differential diagnosis of masses of the lateral forehead and temporal fossa.
      While the first reported case of a temporal artery aneurysm was reported by
      Thomas Bartholin in 1740, there is scant mention of this lesion in the plastic
      and maxillofacial surgical literature. Pseudoaneurysms can arise in the forehead
      and scalp as a result of blunt traumatic impingement of the superficial temporal
      artery against the calvarium. The anterior branch of the artery is most
      vulnerable, because in the lateral forehead it courses over the frontal osseous
      ridge in the galea aponeurotica formed by the fusion line of the deep and
      superficial temporalis muscle fascia. This dense fascial investment has a
      tethering effect in the gap between the temporalis and frontalis muscles and
      prevents the artery from displacing laterally in response to traumatic forces. A
      history of recent blunt trauma or surgery to the forehead, combined with a
      pulsatile bruit, should direct the physician to the diagnosis of pseudoaneurysm
      of the superficial temporal artery. Treatment is surgical resection of the
      involved segment without the need for reconstruction. This report includes a
      review of the literature and presents the first documented case of a bicycle
      helmet as the cause of a superficial temporal artery pseudoaneurysm.

PMID- 8988782
TI  - Acroangiodermatitis (pseudo-Kaposi's sarcoma) associated with Klippel-Trenaunay
      syndrome.
AB  - Acroangiodermatitis is an unusual cutaneous sequela of chronic venous
      insufficiency and congenital vascular malformations of the lower extremities. It
      typically manifests as purple-colored plaques on the extensor surfaces of the
      toes of the affected limb. Histologically, it closely resembles Kaposi's sarcoma
      and had thus been named "pseudo-Kaposi's sarcoma." This is a report of
      acroangiodermatitis in a patient with Klippel-Trenaunay syndrome.

PMID- 8988783
TI  - Noma: a review.
AB  - Cancrum oris or noma is a condition not well known in western Europe and North
      America. It is, however, a relatively common cause of mortality and disability in
      children of undeveloped areas of Africa, Asia, and South America. This paper
      describes the experience at Galmi Hospital, in the sub-Saharan region of South
      Africa in the Niger Republic, with 50 operative patients out of a group of 300
      who were referred. An extensive review of the literature is presented describing
      the epidemiological impact of the disease, the characteristics of the lesions,
      the pathogenesis, symptoms, sequelae, differential diagnosis, and preoperative
      preparation. Additionally, we review approaches to anesthesia, methods of
      reconstruction, and the most common causes of complications and mortality.
      Numerous photographs illustrating the devastating consequences of this problem
      are presented.

PMID- 8988784
TI  - Neovaginoplasty in male transsexuals: review of surgical techniques and
      recommendations regarding eligibility.
AB  - The surgical aim of genital reassignment surgery in male-to-female transsexuals
      is to create a perineogenital complex as feminine in appearance and function as
      possible. In this paper, we present a review of the various methods to line the
      neovagina in male-to-female transsexuals. These methods may be classified in five
      categories involving, respectively, application of nongenital skin grafts, penile
      skin grafts, penile skin flaps, nongenital skin flaps, and pedicled intestinal
      transplants. Based on this review and our extensive personal experience, we come
      to certain recommendations regarding the eligibility of these methods.

PMID- 8988785
TI  - How to harvest a septal chondromucosal graft.
AB  - A simple technique to facilitate easier harvesting of a septal chondromucosal
      graft is presented. Turning over the ala (like a swinging door) using a perialar
      incision greatly helps easy harvesting of the graft under extremely good direct
      vision.

PMID- 8988787
TI  - Re: Is blood transfusion necessary in reduction mammaplasty patients?

PMID- 8988786
TI  - An expresso explosion.

PMID- 8988788
TI  - Re: Is there a plastic surgery beltway?

PMID- 8988789
TI  - Liposculpture with the nasal Fraser suction techniques.

PMID- 8988790
TI  - Ziskind-Somerfeld Research Award 1996. Medial and superior temporal gyral volumes
      and cerebral asymmetry in schizophrenia versus bipolar disorder.
AB  - Prior magnetic resonance imaging (MRI) studies report both medial and lateral
      cortical temporal changes and disturbed temporal lobe asymmetries in
      schizophrenic patients compared with healthy controls. The specificity of
      temporal lobe (TL) changes in schizophrenia is unknown. We determined the
      occurrence and specificity of these TL changes. Forty-six schizophrenic patients
      were compared to 60 normal controls and 27 bipolar subjects on MRI measures of
      bilateral volumes of anterior and posterior superior temporal gyrus (STG),
      amygdala, entorhinal cortex, and multiple medial temporal structures, as well as
      global brain measures. Several regional comparisons distinguished schizophrenia
      from bipolar disorder. Entorhinal cortex, not previously assessed using MRI in
      schizophrenia, was bilaterally smaller than normal in schizophrenia but not in
      bipolar disorder. Schizophrenic but not bipolar patients had an alteration of
      normal posterior STG asymmetry. Additionally, left anterior STG and right
      amygdala were smaller than predicted in schizophrenia but not bipolar disorder.
      Left amygdala was smaller and right anterior STG larger in bipolar disorder but
      not schizophrenia.

PMID- 8988791
TI  - Effect of sertraline on regional metabolic rate in patients with affective
      disorder.
AB  - Seventeen patients with major affective disorder completed a 10-week, placebo
      controlled, randomized trial of the serotonin reuptake inhibitor sertraline.
      Patients underwent positron emission tomography with 18F-deoxyglucose and were
      assessed with the Hamilton Depression Rating Scale at baseline and 10 weeks after
      treatment with sertraline or placebo. The middle frontal gyrus, an area
      previously characterized by decreased metabolic activity in depressive patients,
      showed relatively increased activity on both sides after sertraline when
      contrasted with temporal and some occipital areas. Sertraline was associated with
      a significantly increased relative metabolic rate in right parietal lobe and in
      left occipital area 19, and a decreased metabolic rate in right occipital area
      18. Other areas that differed between controls and a larger cohort of 39
      depressive patients--including medial frontal lobe, cingulate gyrus, and thalamus
      -also showed a normalization of metabolic rate after sertraline.

PMID- 8988792
TI  - Magnetic resonance imaging-based measurement of hippocampal volume in
      posttraumatic stress disorder related to childhood physical and sexual abuse--a
      preliminary report.
AB  - We have previously reported smaller hippocampal volume and deficits in short-term
      memory in patients with combat-related posttraumatic stress disorder (PTSD)
      relative to comparison subjects. The purpose of this study was to compare
      hippocampal volume in adult survivors of childhood abuse to matched controls.
      Magnetic resonance imaging was used to measure volume of the hippocampus in adult
      survivors of childhood abuse (n = 17) and healthy subjects (n = 17) matched on a
      case-by-case basis for age, sex, race, handedness, years of education, body size,
      and years of alcohol abuse. All patients met criteria for PTSD secondary to
      childhood abuse. PTSD patients had a 12% smaller left hippocampal volume relative
      to the matched controls (p < .05), without smaller volumes of comparison regions
      (amygdala, caudate, and temporal lobe). The findings were significant after
      controlling for alcohol, age, and education, with multiple linear regression.
      These findings suggest that a decrease in left hippocampal volume is associated
      with abuse-related PTSD.

PMID- 8988793
TI  - PET brain mapping study of auditory verbal supraspan memory versus visual
      fixation in schizophrenia.
AB  - Changes in regional cerebral blood flow (rCBF), associated with performance of an
      auditory verbal supraspan memory task, were studied in eight remitted DSM-III-R
      schizophrenic patients and eight pair-wise matched normal controls. Four positron
      emission tomography (PET) scans, using the [15O]-H2O technique, were acquired:
      two while subjects fixated a cross hair and two while performing a verbal free
      recall supraspan memory task. Task performance showed typical patterns of recency
      and primacy effects in both groups; however, patients performed more poorly than
      controls on the primary (working) memory aspect of the task. Regions showing rCBF
      changes overlapped in both groups and were similar to those seen in previous
      studies of normals; however, patients had smaller increases in rCBF than controls
      in frontal and superior temporal cortical regions bilaterally. Our results
      suggest that remitted patients with schizophrenia demonstrate impairments of
      capacity-limited information processing, which may be related to metabolic
      dysfunction within a distributed network of brain structures, including the
      prefrontal and temporal cortical regions; however, dysfunction limited to the
      frontal cortex cannot be ruled out by the results of this experiment.

PMID- 8988794
TI  - Visuospatial working memory in patients with schizophrenia.
AB  - Recent investigations have documented abnormalities in working memory related
      processes in schizophrenics on tasks assessing the central executive component of
      this cognitive model. This preliminary study investigated the function of another
      component of the working memory system, the visuospatial scratch pad in
      schizophrenia. The "scratch pad's" passive visual store--responsible for the
      temporary retention of visual material--was assessed via a computerized spatial
      delayed response task, whereas its active spatial rehearsal subsystem-
      specialized for retaining the temporal properties--was explored through visual
      block span. To assess elemental visual spatial abilities we used the Judgment of
      Line Orientation test. Thirty-two schizophrenics and 27 controls were tested.
      Although we discovered the basic perceptual abilities of patients to be intact,
      we determined that whenever memory was necessitated on spatial tasks, patients
      demonstrated marked deficits. This pattern of cognitive dysfunction is consistent
      with impairments in a neural network involving prefrontal and/or posterior brain
      regions in schizophrenia.

PMID- 8988795
TI  - Minimal effects of dextroamphetamine on scopolamine-induced cognitive impairments
      in humans.
AB  - The central anticholinergic drug scopolamine has been used to model aspects of
      the memory impairment that occurs in Alzheimer's disease and in aging. To
      determine whether nonspecific stimulant effects can attenuate the cognitive
      impairment induced by scopolamine, we studied the effects of scopolamine and the
      stimulant dextroamphetamine in 17 young normal volunteers. After a baseline day
      of cognitive testing, subjects participated in two study days, in which they
      received dextroamphetamine (d-AMP) (0.25 mg/kg p.o.) + scopolamine (0.5 mg i.v.)
      and placebo + scopolamine, in randomized order under double-blind conditions.
      There were no statistically significant differences in cognitive test performance
      between the two drug conditions with the exception of one of the category
      retrieval tasks. Stimulant effects were documented to occur by other measures. We
      conclude that d-AMP at the dose used does not attenuate the memory impairment
      induced by scopolamine.

PMID- 8988796
TI  - Lack of behavioral effects of monoamine depletion in healthy subjects.
AB  - This study was designed to determine the behavioral effects of a reduction in
      catecholamine and indoleamine function in healthy subjects. Eight healthy
      subjects received the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine
      (AMPT) in combination with a full-strength tryptophan-depleting amino acid drink
      during one 4-day test session, and AMPT and tryptophan-supplemented amino acid
      drink (n = 2), or a 25% strength tryptophan-depleting amino acid drink (n = 6)
      during a second 4-day test session. The combined administration of AMPT and the
      tryptophan-free amino acid drink did not produce statistically significant or
      even clinically noticeable changes in mood among the healthy subjects. The
      implications of these observations for the monoamine hypotheses of depression are
      discussed.

PMID- 8988797
TI  - Pregnancy, delivery and infancy complications and attention deficit hyperactivity
      disorder: issues of gene-environment interaction.
AB  - We evaluated the role of pregnancy, delivery, and infancy complications (PDICs)
      in the etiology of attention deficit hyperactivity disorder (ADHD) and addressed
      issues of comorbidity and familiarity by testing multiple hypotheses. Subjects
      were 6-17-year-old boys with DSM-III-R ADHD (n = 140) and normal controls (n =
      120) and their first-degree biologic relatives. Information on PDICs was obtained
      from mothers in a standardized manner blind to the proband's clinical status.
      Using linear and logistic regression models, a positive association was found
      between ADHD and PDICs in the probands. Additionally, PDICs were associated with
      the correlates of ADHD (i.e., impaired cognitive functioning and poor school
      performance). Moreover, it was those specific complications that reflect chronic
      exposure, such as maternal bleeding, smoking, family problems, and illicit drug
      use during pregnancy that accounted for these findings. No interaction between
      genetic factors and PDICs were found. Our findings add to the literature
      supporting an association between ADHD and PDICs. Our results may help clinicians
      focus on particular complications rather than the wide range of possible
      perinatal complications.

PMID- 8988798
TI  - Adrenocorticotropic hormone and cortisol responses to corticotropin-releasing
      hormone: changes in panic disorder and effects of alprazolam treatment.
AB  - This study applied the corticotropin-releasing hormone (CRH) stimulation test to
      patients with panic disorder, before and during treatment with alprazolam, and to
      control subjects. In contrast to some, but not all prior studies, untreated,
      nondepressed panic disorder patients failed to show blunted adrenocorticotropic
      hormone or cortisol responses to CRH. In fact, the responses were subtly enhanced
      in that they were more rapid than those of controls. After 12 weeks of alprazolam
      treatment, repeat testing gave results that were indistinguishable from those of
      controls. Inconsistency among reports of CRH testing in panic disorder may be
      related to interactions among illness mechanisms, concurrent subthreshold
      depressive symptoms, the chronic stress of the illness, and hyperresponsiveness
      of panic patients to the acute stress of experimental manipulations. Pretreatment
      abnormalities in hypothalamic-pituitary-adrenal axis function appear to resolve
      with alprazolam treatment. Preliminary observations suggest that pretreatment
      dysregulation of the hypothalamic-pituitary-adrenal system may predict a more
      difficult or less satisfactory treatment.

PMID- 8988799
TI  - The anatomy of mood disorders--review of structural neuroimaging studies.
AB  - The structural neuroimaging findings in mood disorders were reviewed, to evaluate
      evidence for a neuroanatomic model of pathophysiology, involving the prefrontal
      cortex, the basal ganglia, the amygdala-hippocampus complex, thalamus, and
      connections among these structures. Global atrophy is not consistently found. The
      best replicated finding is an increased rate of white matter and periventricular
      hyperintensities. A smaller frontal lobe, cerebellum, caudate, and putamen appear
      present in unipolar depression. A larger third ventricle, and smaller cerebellum
      and perhaps temporal lobe appear present in bipolar disorder. These localized
      structural changes involve regions that may be critical in the pathogenesis of
      mood disorders. Generalized and localized anatomic alterations may be related to
      age or vascular disease. The clinical and biological correlates of these changes
      need to be investigated to allow development of a more complete model of
      pathophysiology of mood disorders.

PMID- 8988800
TI  - Elevated lymphocyte spiperone binding: a vulnerability factor for affective
      psychosis?

PMID- 8988801
TI  - Electrodermal activity as a prodromal sign in schizophrenia.

PMID- 8988802
TI  - Treatment of long-term tardive dyskinesia with vitamin E.

PMID- 8988803
TI  - A preliminary study of tryptophan depletion on tics, obsessive-compulsive
      symptoms, and mood in Tourette's syndrome.

PMID- 8988804
TI  - Diazinon toxicokinetics, tissue distribution and anticholinesterase activity in
      the rat.
AB  - The toxicokinetics, tissue distribution, and anticholinesterase (antiChE)
      activity of diazinon were investigated in the rat. Plasma concentrations most
      adequately fitted a two-compartment open model after i.v. administration of 10
      mg/kg and a one-compartment model after oral administration of 80 mg/kg. Diazinon
      elimination half-life following i.v. and oral dosing was 4.70 and 2.86 h,
      respectively. The oral bioavailability was found to be low (35.5%). Hepatic
      extraction ratios after i.v. administration of 5 or 10 mg/kg were 54.8% and
      47.7%, respectively, suggesting that low systemic oral bioavailability can be
      explained by a first-pass effect in the liver. Diazinon was found to be
      approximately 89% protein-bound in plasma within the concentration range 0.4-30
      ppm. The highest concentration of diazinon after i.v. administration was found in
      the kidneys, when comparing to liver, kidney, brain. Both red blood cell (RBC)
      acetylcholinesterase (AChE) and plasma ChE activities were inhibited rapidly (44%
      and 17% at 10 min, and 36% and 13% min for i.v. and oral administration,
      respectively), but inhibition of RBC AChE was greater than that of plasma ChE.

PMID- 8988805
TI  - Presence of antibodies to heat stress proteins and its possible significance in
      workers exposed to high temperature and carbon monoxide.
AB  - Antibodies to the ubiquitous group of stress proteins known as heat shock
      proteins (Hsps) have been found to be associated with a number of diseases in
      humans. Hsps are known to be induced by certain xenobiotics, some of which are
      common in the working environment. The biological significance of the presence of
      such autoantibodies is presently unclear. In the present study, we used
      immunoblotting to investigate the presence of antibodies against the different
      stress proteins, Hsp27, Hsp60, Hsp71, Hsc (heat shock cognate) 73 and Hsp89 alpha
      and beta in groups of workers exposed to high temperature or carbon monoxide.
      These data were related to a detailed clinical evaluation and to various
      laboratory measurements including electrocardiogram (ECG), B echogram, white
      blood cell counts and typing, the activity of alanine aminotransferase (ALT),
      acid phosphatase (ACP) and alkaline phosphatase (ALP) and lymphocyte DNA damage.
      Antibodies to Hsp27 and Hsp71 were found more frequently in the high temperature
      and carbon monoxide-exposed groups than in controls (P < 0.05). The carbon
      monoxide-exposed group showed the highest incidence of anti-Hsp antibodies. Anti
      Hsp60 antibodies were only detected in workers exposed to high temperature or
      carbon monoxide. The percentage of workers with abnormal ECG, B echogram changes
      and displaying hepatitis B antigen (HBsAg) was higher in the carbon monoxide
      group than in the control group (P < 0.05). There was a significant increase in
      the activity of ALT in the high temperature and carbon monoxide groups and in the
      activities of ACP and ALP in the carbon monoxide group (P < 0.05). The extent of
      DNA damage measured in lymphocytes was higher in workers from the high
      temperature and carbon monoxide-exposed groups. We suggest that the increased
      frequency of antibodies to Hsps is the result of these damages of the release of
      denatured Hsps and of a decrease in the phagocytic ability of macrophages in
      these workers. The data gathered in the present study show a statistical relation
      between the occurrence of antibodies against Hsps and the frequency of health
      problems in workers and suggest a potential role for the antibodies as useful
      biomarkers to assess whether workers are experiencing environmental stress.

PMID- 8988806
TI  - Age-related metabolic effects of acetaldehyde on rats with reference to
      detoxification enzymes and sulfhydryl groups.
AB  - Induced-acetaldehyde toxic effects on gluatathione [GSH] metabolism and
      sulfhydryl (SH) groups in liver and in brain of female albino rats with reference
      to age was studied. The total -SH groups were decreased whereas the specific
      activities of glutathione-S-transferase [GST] and glutathione peroxidase [GPo]
      were increased in acetaldehyde treated rats. However, the specific activity
      levels of glutathione reductase [GR] and gamma-glutamylcysteine synthetase [gamma
      GCS] were decreased. In general, acetaldehyde induced changes in the specific
      activities of the enzymes that increase with increasing age.

PMID- 8988807
TI  - Carotenoid analysis of several dark-green leafy vegetables associated with a
      lower risk of cancers.
AB  - We have examined the carotenoid contents of several dark green vegetables found
      to be associated with a lower risk of various epithelial cancers in our
      epidemiological study and animal study. Samples of these vegetables were
      quantitatively examined by high-performance liquid chromatography (HPLC) on a C
      18 reversed-phase column for individual carotenoid content. Pure reference
      compounds (alpha-carotene, beta-carotent, lycopene, canthaxanthin, and lutein)
      and internal standard (beta-Apo-8'-carotenal) were employed to quantify
      xanthophylls and carotenes in these vegetables. The results indicated that fresh,
      dark-green, leafy vegetables were high in beta-carotene (0.94-9.36 mg/100 g) and
      oxygenated carotenoids or xanthophylls, primarily lutein (0.94-7.39 mg/100 g),
      whereas lycopene and alpha-carotene were not prominent and canthaxanthin was non
      existent in these vegetables. These analyses suggest that consumption of
      carotenoids such as lutein in addition to beta-carotene may be associated with a
      lower risk of cancers.

PMID- 8988808
TI  - Effect of repetitive bleeding on NADH-cytochrome b5 methemoglobin reductase
      activity and molybdenum content in erythrocytes in rats.
AB  - Reticulocytosis in rats was induced by repetitive bleeding. Both in the vitro and
      the in vivo studies showed that the detected reductive speed of methemoglobin of
      the bleeding group was faster than that of the control group at all time
      intervals. At the same time, the NADH-cytochrome b5 methemoglobin reductase
      activity and the molybdenum content in erythrocytes of the bleeding group were
      significantly increased. Regressional analysis showed that there was a
      significantly positive correlation between the enzyme activity and the molybdenum
      content. It is proposed that molybdenum might be required for the enzyme
      activity.

PMID- 8988809
TI  - Removal of heavy metals by two free floating aquatic macrophytes.
AB  - A concentration-dependent decrease in biomass, protein, RNA, DNA, and nutrient
      (NO3(-) and PO4(3-)) uptake of Lemna minor and Azolla pinnata by Cr, Ni, and Zn
      was detected. Cr was found to exert maximum toxicity followed by Ni and Zn. Metal
      uptake was dependent on time and concentration of metal in the external medium.
      Both the macrophytes, however, showed preference for Zn followed by Ni and Cr.
      The uptake kinetics also revealed a low Vmax and high Km for Cr. L. minor was
      more efficient in accumulating Zn and Cr than A. pinnata in Ni. Compared to
      immobilized algae and bacterial capsules the test macrophytes showed a greater
      efficiency for metal removal.

PMID- 8988810
TI  - Embryonic hypertension following exposure to teratogenic doses of 5-fluoro-2'
      deoxyuridine.
AB  - The teratogenicity of 5-fluoro-2'-deoxyuridine (FdU) is well established.
      Previously, we have demonstrated that teratogenic doses of FdU produce hematomas
      and suggested that those hematomas produced skeletal malformations in chicken
      embryos. In this study, the cardiovascular effects of teratogenic doses of FdU in
      chicken embryos were studied. A dose of either 0.026 micrograms FdU or 0.030
      micrograms FdU was injected into the yolk sacs of fertile chicken eggs containing
      embryos at Hamburger and Hamilton stages 17-19 of development. The embryos were
      then returned to the incubator. Aortic systolic and diastolic blood pressure,
      blood velocity and heart rate were measured at stages 21, 24 or 27 using a
      servonull system and Doppler ultrasound. In addition, mean arterial blood
      pressure, blood flow, and stroke volume were calculated from these data. Similar
      data were also recorded from uninjected and saline injected control embryos.
      Systolic and mean arterial blood pressures were significantly increased in FdU
      treated embryos at stage 27. The other parameters measured or calculated were not
      significantly different from control embryos. Our study suggests that elevated
      systolic blood pressure in chicken embryos treated with FdU may lead to hematoma
      formation and subsequent birth defects.

PMID- 8988812
TI  - A preliminary study of C-reactive protein in the diagnosis and monitoring of Lyme
      disease.
AB  - Concentrations of C-reactive protein (CRP) in the serum of 14 patients suffering
      from Lyme disease were measured. 86% of these patients were found to have
      abnormally high concentrations of serum CRP (range 14-158 mg/L). The CRP
      concentration of a 60-year-old patient abated from 29 mg/L to 13 mg/L after
      treatment. Results suggest that serum CRP concentration can provide a valuable
      and accurate means for the clinical diagnosis and monitoring of Lyme disease.

PMID- 8988811
TI  - The use of enzyme-digested soybean residue for feeding common carp.
AB  - This experiment was an attempt to use the soybean residue derived from the
      production of "soy milk". The residue contains about 18% protein, 70%
      carbohydrates and 7.5% lipid as fish feed for rearing common carp, Cyprinus
      carpio. There were 4 types of diets: (1) soybean residue, (2) soybean residue
      digested with Papain, (3) soybean residue (64%) mixed with beef liver (34%) and
      (4) same mixture as (3) but digested with Papain. The results indicate that the
      percentage increase in weight and length of fish feeding with beef liver
      supplemented diets was higher than those feeding with soybean residue alone. This
      was possibly due to the fact that beef liver was able to supplement the nutrient
      deficiency in soybean. The two types of feeds (2 and 4) digested with Papain also
      yielded significantly better fish growth in terms of weight and length gains,
      than their counterparts without digestion. Furthermore, the water turbidity of
      the tanks added with digested feeds was significantly less, as Papain was able to
      hyrolyse the protein substrates suspended in the water, and thus lowered the
      turbidity.

PMID- 8988813
TI  - Effect of acetaldehyde on oxidoreductases in tissues of rats at different ages.
AB  - The toxicity of acetaldehyde and age related changes on oxidoreductases in the
      liver, brain, kidney, and muscle of female albino rats (Wistar strain) were
      studied. The specific activities of lactate [LDH], isocitrate [ICDH (NAD/NADP)],
      succinate [SDH], malate [MDH], glutamate [GDH] and glucose-6-Phosphate [G-6-PDH]
      dehydrogenases were significantly increased as a function of age. However,
      acetaldehyde treatment significantly inhibited oxidoreductases in the tissue of
      21, 90 and 180 day old rats. Liver enzymes of young (21 days) rats exhibited
      greater sensitivity to acetaldehyde toxicity. Similar inhibition of
      oxidoreductases in brain and kidney of adult (180 days) rats treated with
      acetaldehyde was observed. LDH and GDH as compared to other enzymes studied
      showed higher susceptibility to acetaldehyde toxicity. The differential
      sensitivity of tissues and inhibition of oxidoreductases by acetaldehyde as a
      function of age could be attributed to hypoxic conditions, energy crisis, and
      mitochondrial structural changes. The results suggest that acetaldehyde affects
      oxidation of glucose via HMP shunt pathway, glycolytic pathways and Krebs cycle
      resulting in the impairment of carbohydrate metabolism.

PMID- 8988814
TI  - The distribution of HgCl2 in rat body and its effects on fetus.
AB  - Both female and male Wistar rats were dividend into 3 groups according to their
      body weights. The two test groups were given 75 micrograms/ml and 7.5
      micrograms/ml HgCl, respectively, via drinking water, while the control group was
      given distilled water. Animals were mated after the male rats were treated for 12
      weeks and female rats for 2 weeks. Blood samples from rats were taken on the 18th
      day of the pregnancy and the results showed that the HgCl2 was absorbed and
      stored in the blood in the form of inorganic mercury. The greatest amount of
      HgCl2 was found in the kidney. The placenta and the tests also had high mercury
      deposits. Fetuses showed low levels of HgCl2, thus, the placenta appears to serve
      as a barrier against HgCl2. No pathological changes were observed in the
      placenta, ovary, liver, and kidney in the female rats, but the epithelial cells
      of the rental proximal convoluted tubules were cloudy and swelling. The renal
      corpuscle showed no changes in the male rats. Pathological examination showed
      that a portion of the seminiferous epithelia were falling off, and the number of
      sperm released by the male was reduced. Examination by electron microscopy
      revealed that particulate fat was increased in sperm cells, which suggests that
      spermatozoa had been degenerated and were possibly one of the causes for the
      decreased rates of pregnancy in the exposed groups. No malformation of organs and
      bones in the rat fetuses were observed.

PMID- 8988815
TI  - CJA--metamorphosis.

PMID- 8988816
TI  - Anaesthesia technology: friend and foe.

PMID- 8988817
TI  - The hypertensive response to intubation. Do researchers acknowledge previous
      work?
AB  - PURPOSE: To see whether investigators of a circumscribed research topic, the
      haemodynamic response to orotracheal intubation, review and cite previous work. A
      1989 editorial about the response was critical to investigators for measuring
      physiology but not outcome; for nonetheless making recommendations; for studying
      only patients not at risk; and for implying patients are at risk when this is not
      certain. METHODS: A systemic Medline search was made for English language reports
      published during or after 1990, and their citation lists read for missed reports.
      All retrieved papers were read for citation of the editorial and for
      acknowledgement of its criticisms. Citations were tabulated, and cross-referenced
      between papers, to see whether blocks of citations had been obtained from other
      investigators' reports. RESULTS: Eighty-one full reports, from 48 groups of
      investigators, were obtained. The 1989 editorial was cited twice. All studies
      included physiological measurements, but none reported long-term outcome. There
      was no comment on the need to know outcome in 39 reports. Pre-existing risk
      factors were exclusions in 65 studies. In 56 papers, complications of the
      response were given as the reason for the study; in 41 of these papers only
      healthy subjects were studied. In total, 249 references about the response were
      identified from the 81 papers. There was no obvious evidence that citations were
      obtained from others' papers. CONCLUSION: Recognised deficiencies in research
      method were not acknowledged. When submitting work for publication, investigators
      should provide evidence of how they searched for previous work.

PMID- 8988818
TI  - Quality and retrieval of obstetrical anaesthesia randomized controlled trials.
AB  - PURPOSE: Randomized controlled trials (RCTs) are suitable for meta-analysis and
      systematic reviews provided they are of high quality and are easy to retrieve. We
      determined these attributes of RCTs in obstetrical anaesthesia in a sample of
      available journals that are indexed in MEDLINE. SOURCE: Randomized controlled
      trials published between January 1985 and December 1994 in seven anaesthetic and
      three obstetric journals were identified by a MEDLINE search, and by handsearch
      of the same journals. Each RCT was assigned a quality score by a blinded rater
      using a reliable and validated scaled. The quality of each RCT was described and
      compared over time and by journal. The comparative yield of MEDLINE and hand
      search was evaluated. PRINCIPAL FINDINGS: Three hundred and forty RCTs were
      retrieved by MEDLINE and handsearch. Two hundred and twenty seven (65%) were
      identified by the MEDLINE search and 333 by the handsearch (98%). The median
      quality score was 3/5. There was no difference in score over time. Anesthesiology
      had the highest median score, Anaesthesia had the lowest (P < 0.05). CONCLUSIONS:
      Care must be taken when reviewing obstetrical anaesthesia research. Strategies in
      addition to a MEDLINE search must be used to identify RCTs since more than one
      third were missed using MEDLINE alone. Poor quality RCTs are more likely to be
      biased in favour of a new treatment. Therefore, to increase the validity of
      reviews sensitivity analyses based on quality should be done.

PMID- 8988819
TI  - Dose-response to anaesthetic induction with sufentanil: haemodynamic and
      electroencephalographic effects.
AB  - PURPOSE: To determine the effect of a five-fold variation in sufentanil dose on
      the haemodynamic and electroencephalo graphic (EEG) response to anaesthetic
      induction and tracheal intubation. METHODS: Thirty-four patients undergoing
      elective coronary artery bypass grafting (CABG) participated in this randomized
      double-blind study. Patients in Group L (n = 17) received 3 micrograms.kg-1
      sufentanil and those in Group H (n = 17) 15 micrograms.kg-1. Premedication was 60
      micrograms.kg-1 lorazepam po. Anaesthesia and neuromuscular blockade were induced
      by infusing sufentanil and 0.15 mg.kg-1 vecuronium i.v. over five minutes.
      Haemodynamic data and the electroencephalographic (EEG) spectral edge were
      acquired by computer and compared at Control, Induction and Intubation. RESULTS:
      Sufentanil dose did not affect the haemodynamic or EEG response at end-induction.
      No bradyarrhythmias occurred, and the incidence of hypotension was 12% in both
      groups. However, during induction apparent electromyographic artifacts and a
      transiently greater increase in heart rate were observed in Group H. The serum
      sufentanil concentration at Induction was 6.1 +/- 1.8 ng.ml-1 in Group L and 25.4
      +/- 8.8 ng.ml-1 in Group H, and did not correlate with haemodynamic changes. No
      patient recalled any intraoperative event. CONCLUSION: Increasing sufentanil dose
      from 3 to 15 micrograms-1 does not influence the ultimate haemodynamic response
      to induction. Combined with lorazepam premedication, 3 micrograms-1 sufentanil
      produces near-maximal haemodynamic and EEG effects and is adequate for induction
      and tracheal intubation of patients undergoing CABG. Sufentanil 15 micrograms.kg
      1 is no more efficacious, and causes transient cardiovascular stimulation.

PMID- 8988820
TI  - Conscious sedation for interventional neuroradiology: a comparison of midazolam
      and propofol infusion.
AB  - PURPOSE: The aim of this study was to compare two conscious sedation techniques,
      midazolam (M) and propofol (P), for interventional neuroradiology by assessment
      of the incidence of complications and satisfaction scores. METHODS: Forty
      patients were randomized to receive 0.75 micrograms.kg-1 fentanyl and a M or P
      bolus followed by an infusion (M 15 micrograms.kg-1 + 0.5 micrograms.kg-1.min-1;
      P 0.5 mg.kg-1 + 25 micrograms.kg-1 min-1). The incidences of complications and
      untoward events requiring intervention were documented. These included
      respiratory depression, excessive pain, inappropriate movements and the inability
      to examine the patient. The satisfaction of the anaesthetic technique from the
      perspective of both the neuroradiologist and the patient was scored. RESULTS: The
      incidence and types of complications were no different between the two groups.
      Pain occurred in 12 patients (6M, 6P), inappropriate movements in 17 (7M, 10P)
      and respiratory changes in 10 patients (2M, 8P). CONCLUSIONS: Both techniques
      were satisfactory and the incidence of complications was similar for both groups.

PMID- 8988821
TI  - Pre-emptive analgesia with ketamine, morphine and epidural lidocaine prior to
      total knee replacement.
AB  - PURPOSE: Pre-emptive analgesia can improve postoperative pain management. The
      purpose of this study was to examine the effectiveness of ketamine as a pre
      emptive analgesic as previous studies have shown the involvement of N-methyl-D
      Aspartate (NMDA) receptor in neuroplasticity. METHODS: Forty-five ASA 1-2
      patients, undergoing unilateral total knee replacement were studied. In the study
      groups, epidural lidocaine was used as the primary anaesthestic. Patients
      received ketamine + morphine epidurally 30 min either before (group EB) or after
      skin incision (group EA). Group G patients received general anaesthesia and
      ketamine + morphine were given 30 min after skin incision via an epidural
      catheter used for postoperative pain control. Epidural morphine and ketamine in
      lidocaine was given to all patients at the end of surgery and every 12 hr for
      three days for analgesia supplemented with PCA morphine. The time until first PCA
      trigger, morphine consumption, pain scores, satisfaction scores, and morphine
      related side effects were recorded at 6, 12, 24, 48 and 72 hr after surgery.
      RESULTS: Epidural ketamine plus morphine with lidocaine before surgical incision
      produced better pain relief and patient satisfaction than when given after
      incision. A longer time to PCA and decreased morphine consumption were observed
      in group EB than in group G. In group EA, epidural anaesthesia also produced some
      pre-emptive analgesic effect compared with general anaesthesia shown by decreased
      morphine consumption. CONCLUSIONS: Administration of ketamine plus morphine with
      epidural lidocaine anesthesia before surgery provided improved postoperative
      analgesia compared with general anaesthesia alone or when analgesics were given
      after skin incision.

PMID- 8988822
TI  - Interleukin-10 and interleukin-1 receptor antagonists increase during cardiac
      surgery.
AB  - BACKGROUND: It has been reported that inflammatory cytokines such as interleukin
      8 and 6 (IL-8, IL-6) increase during cardiac surgery and caused postoperative
      cardiac dysfunction. Therefore, it is important to investigate changes of
      suppressive cytokines such as IL-10, interleukin-4 (IL-4) and interleukin-1
      receptor antagonist (IL-1ra) during cardiac surgery. METHOD: Serum levels of
      cytokines and IL-1ra were measured in 10 patients during cardiac surgery with
      cardiopulmonary bypass. Six blood samples were drawn after inducing anaesthesia.
      In each sample, serum IL-10, IL-4, IL-8, IL-6 and IL-1ra were measured by enzyme
      linked immunosorbent assay. RESULTS: Serum IL-6 and IL-8 concentration (19.1 +/-
      8.8 pg.ml-1, and 13.4 +/- 5.2 pg.ml-1, preoperatively) increased to 227.5 +/- 191
      pg.ml-1 and 81.0 +/- 56 pg.ml-1 at 60 min after declamping aorta (P < 0.01,
      respectively). Serum IL-10 concentration increased at 60 min after declamping the
      aorta compared with the preoperative value (from 1.0 +/- 0 pg.ml-1 to 552.0 +/-
      158 pg.ml-1 P < 0.001]). Similarly, serum IL-1ra concentration increased from the
      preoperative value of 1331 +/- 896 pg.ml-1 to 43353 +/- 12812 pg.ml-1 at 60 min
      after declamping the aorta (P < 0.001). Positive correlations were obtained
      between IL-10 and IL-8, and between IL-10 and IL-6 (gamma = 0.7, gamma = 0.8, P <
      0.001, respectively). CONCLUSION: These findings demonstrate that pro- and anti
      inflammatory cytokines increase to maintain their balance during cardiac surgery.

PMID- 8988823
TI  - Music increases satisfaction in elderly outpatients undergoing cataract surgery.
AB  - PURPOSE: Music has long been known to reduce anxiety, minimize the need for
      sedatives, and make patients feel more at ease. The purpose of the study was to
      evaluate the effect of music in elderly outpatients undergoing elective cataract
      surgery with retrobulbar block and monitored anaesthetic care using fentanyl or
      alfentanil and midazolam. METHODS: One hundred and twenty one patients were
      prospectively and randomly assigned to hear: relaxing suggestions, white noise,
      operating room noise or relaxing music via audio-cassette headphones. Vital signs
      were documented before and after retrobulbar block and every 15 min thereafter.
      Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) before and
      after surgery. Visual analogue scales (VAS) were used to assess anxiety and
      patient satisfaction postoperatively with a standardized questionnaire. Between
      group comparisons were made using Chi-Square, or ANOVA, where appropriate.
      RESULTS: There were no differences between groups in STAI or anxiety VAS scores
      at any time. Differences were noted in systolic blood pressure, but not in other
      vital signs. Patients' ratings of the whole operative experience, satisfaction
      with the tape played, general level of relaxation and preference for the chosen
      tape for subsequent surgery were different (music > relaxing suggestions > white
      noise and OR noise, P < 0.05). CONCLUSIONS: Elderly patients undergoing cataract
      surgery under retrobulbar block were more satisfied with their experience if they
      heard relaxing music, rather than relaxing suggestions or white noise or OR
      noise. The type of auditory stimuli to which the patients were exposed did not
      influence the level of anxiety.

PMID- 8988824
TI  - Intubating conditions and neuromuscular block after divided dose mivacurium or
      single dose rocuronium.
AB  - PURPOSE: To evaluate the tracheal intubating conditions and neuromuscular
      blocking characteristics of divided dose mivacurium or single dose rocuronium.
      METHODS: Thirty-two patients undergoing elective surgery were studied.
      Anaesthesia was with propofol 2 mg.kg-1, followed by an infusion of 150
      micrograms.kg-1.min.1. Patients were randomized to receive either mivacurium-0.15
      mg.kg-1 followed 30 sec later by 0.1 mg.kg-1, or rocuronium- 0.9 mg.kg-1,
      followed 30 sec later by placebo. Tracheal intubating conditions were assessed 90
      sec after the initial dose of relaxant by an anaesthetists who was unaware of
      patient group. The electromyographic (EMG) response of the first dorsal
      interosseus muscle to ulnar nerve train-of-four was measured. RESULTS: Successful
      tracheal intubation was performed in all patients after both mivacurium and
      rocuronium. Intubating conditions (jaw relaxation, open visible vocal cords) were
      judged to be good-excellent in all but one patient before insertion of the
      tracheal tube. However, patients receiving mivacurium were more likely to
      experience coughing and bucking after tracheal tube insertion (10/16 patients)
      than those receiving rocuronium (3/16 patients, P < 0.05). No patient in the
      rocuronium group experienced moderately vigorous coughing and bucking after
      insertion of the tracheal tube vs six patients in the mivacurium group (P <
      0.05). Time to 10 and 25% recovery of neuromuscular function was faster (P <
      0.05) after divided dose mivacurium (20 +/- 1 and 23 +/- 1 min, respectively)
      than after rocuronium (45 +/- 5 and 57 +/- 8 min, respectively). CONCLUSION: The
      results suggest that, during conditions of the study, divided dose mivacurium is
      not recommended for a 90-sec tracheal intubation in patients where moderate
      coughing and bucking is deemed unacceptable.

PMID- 8988825
TI  - Videotape feedback in teaching laryngoscopy.
AB  - PURPOSE: To evaluate if videotape feedback provides educational insights for
      students learning laryngoscopy that they would not otherwise perceive. METHODS:
      Twenty-six medical students were videotaped while performing laryngoscopy for
      oral intubation. Before and after reviewing their performance on the videotape,
      they answered a standardized questionnaire assessing the adequacy of positioning,
      head movement during laryngoscopy, degrees of neck flexion and head extension,
      time elapsed, and whether the laryngoscope contacted the upper lip or teeth.
      After the review, they were asked if being videotaped was distracting, whether it
      provided new instructional insights and, if so, which was most important.
      RESULTS: Only 4% of students felt that initial head and neck positioning was
      suboptimal and this increased to 38% after videotape review (P = 0.029). The
      perceived inadequacy of positioning seemed related to initial overestimation of
      head extension (34.0 +/- 15 degrees) compared with that seen on videotape (21.5
      +/- 13.5 degrees, P = 0.003). The estimated duration of laryngoscopy was
      underestimated (55 +/- 32 sec vs. 75 +/- 29 sec, P = .024) before videotape
      review. Although 26.9% (7/26) of students admitted feeling distracted by the
      video camera, all felt the experience had educational value. CONCLUSION:
      Videotape feedback changed students' perception of how they performed
      laryngoscopy. In particular, head extension was overestimated and duration of
      laryngoscopy underestimated.

PMID- 8988826
TI  - Septic shock.
AB  - PURPOSE: Many patients with sepsis require surgery for their management, often on
      an urgent or emergency basis. Anaesthetists are commonly required to manage
      patients with sepsis and septic shock in the operating room, past anaesthesia
      recovery area, and the intensive care unit. Since little has been written in the
      Anaesthesia literature on sepsis and septic shock, a review of this topic was
      considered appropriate. SOURCE: References were obtained from computerized
      searches on the National Library of Medicine (English language), recent review
      articles and personal files. PRINCIPLES FINDINGS: Septic shock is a common cause
      of morbidity and mortality. Its presentation may be subtle or catastrophic.
      Successful management depends on an understanding of the pathophysiology of the
      syndrome, allowing rapid, appropriate resuscitation. This often requires
      aggressive correction of volume deficit, maintenance of adequate perfusion
      pressure with inotropic and vasopressor therapy, mechanical ventilation and
      correction of coagulopathy. Appropriate cultures must be taken and antibiotic
      therapy started, often empirically. Anaesthetic management should include careful
      haemodynamic monitoring. Anaesthesia induction and maintenance must be tailored
      to the haemodynamically unstable patient. CONCLUSIONS: The management of the
      septic patient in the perioperative period presents a challenge for the
      anaesthetist. Haemodynamic and respiratory instability should be anticipated.
      Management requires multisystem intervention and careful anesthetic management.

PMID- 8988827
TI  - Recall after total intravenous anaesthesia due to an equipment misuse.
AB  - PURPOSE: To present a case of recall after total intravenous anaesthesia (TIVA)
      with propofol-alfentanil infusions to point out an uncommon misuse of the Bard
      InfusOR syringe driver. CLINICAL FEATURES: A healthy patient underwent diagnostic
      dilatation and curettage and laparoscopy for lysis of peritoneal adhesions. After
      induction, anaesthesia was maintained with propofol-alfentanil infusions using
      the Bard InfusOR syringe drivers. Ten minutes into maintenance, the patient was
      moving. The flashing green light confirmed delivery of the medication and the
      alarms were not activated. However, the latch of the movable lever in the
      propofol syringe driver was found to be improperly positioned at the top of the
      plunger and only a small amount of propofol had been delivered. Postoperatively,
      the patient could recall the abdomen being touched during laparoscopy. An
      explanation was given and the patient was satisfied. CONCLUSION: The Bard InfusOR
      syringe driver is not designed to detect a malposition of the lever on the
      syringe plunger. The anaesthetist must ensure proper placement of the lever and
      visual confirmation of medication delivery in order to prevent awareness due to
      this particular problem.

PMID- 8988828
TI  - Negative pressure induced airway and pulmonary injury.
AB  - PURPOSE: To describe negative pressure injury occurring during the use of a
      laryngeal mask airway (LMA) in which airway bleeding rather than pulmonary oedema
      was the major complication. CLINICAL FEATURES: A patient presented to the day
      surgery unit for resection of a ganglion cyst on her right wrist. She underwent
      general anaesthesia using an LMA, and experienced severe laryngospasm and
      transient hypoxaemia (oxygen saturation to 66%) seven minutes after incision.
      This resolved within 90 sec of succinylcholine administration. Nonetheless, the
      LMA was removed, a tracheal tube was inserted atraumatically and positive
      pressure ventilation was maintained until the time of emergence, when fresh blood
      appeared in the tracheal tube. The blood ultimately became frothy, resembling
      pulmonary oedema fluid. Haemoptysis, continued postoperatively and led to the
      hospitalization of this ambulatory patient. CONCLUSION: Rapid development of
      large subatmospheric pressures, as can occur during severe laryngospasm, may
      disrupt the tracheobronchial vasculature causing airway bleeding. This bleeding
      should be distinguished from negative pressure pulmonary oedema.

PMID- 8988829
TI  - Increased cis-atracurium requirements during prolonged administration to a child.
AB  - PURPOSE: To report increase infusion requirements of cis-atracurium during
      prolonged infusion (six weeks) to provide neuromuscular blockade in a child
      during prolonged mechanical ventilation. Despite a previous study in adult
      patients which demonstrated no increase in infusion requirements over five days,
      we noted a considerable increase over six weeks. CLINICAL FEATURES: A seven month
      old infant required prolonged mechanical ventilation and neuromuscular blockade
      following an episode of multi-system organ failure from pseudomembranous colitis.
      The infusion of cis-atracurium was adjusted according to the train-of-four
      response obtained with a peripheral nerve stimulator using standard train-of-four
      monitoring. Initial infusion requirements which were 2.8 micrograms.kg-1 min-1 on
      day #1 increased to 22.3 micrograms.kg-1 min-1 on day #40. CONCLUSION: Increased
      infusion requirements were necessary during the prolonged administration of cis
      atracurium to a critically ill infant. Titration of the dose based on monitoring
      with a peripheral nerve stimulator is recommended.

PMID- 8988830
TI  - Spinal somatosensory evoked potentials after epidural isoproterenol in awake
      sheep.
AB  - PURPOSE: The use of 10-15 micrograms epinephrine as an epidural test-dose is
      controversial. Isoproterenol would be a better alternative. However, before 5
      micrograms isoproterenol can be incorporated in an epidural test-dose,
      neurotoxicological studies have to be performed. The present study was designed
      to assess spinal somatosensory evoked potentials (spinal SSEP) before and after
      epidural isoproteronol. METHODS: Spinal SSEPs were recorded before, 30 min after,
      and 72 hr after 50 micrograms isoproterenol were given epidurally (L3-4) to six
      chronically instrumented awake sheep. The spinal SSEPs after epidural (L3-4)
      administration of 15 ml lidocaine 2% were used to evaluate the model. The SSEPs
      were generated by transcutaneous stimulation of the sciatic nerve in the thigh.
      Spinal SSEPs were recorded directly from the spinal cord at vertebra T12 using a
      monopolar epidural electrode referenced to a subcutaneous needle electrode in the
      adjacent paraspinal area. RESULTS: Thirty minutes and 72 hr after epidural
      injection of 50 micrograms isoproterenol the latency and the amplitude of the
      SSEP waves were similar to baseline values. After lidocaine, no SSEPs could be
      generated in three sheep while in three sheep the latency of wave 2 (W2) was
      prolonged and the amplitude diminished. CONCLUSION: Administration of epidural
      isoproterenol did not affect spinal SSEPs in this study indicating an absence of
      neurotoxic side effects.

PMID- 8988831
TI  - Halothane and isoflurane enhance melanoma tumour metastasis in mice.
AB  - PURPOSE: To investigate the incidence of tumour metastasis from B16 melanoma
      tumour cells in experimental animals following exposure to equipotent
      concentrations of halothane or isoflurane, and to differentiate if exposure to
      one anaesthetic resulted in greater metastases than the other. METHODS:
      Experimental animals (C57B1 mice), were randomized to receive 1.3 MAC hours of
      halothane or isoflurane anaesthesia. The control group of animals received oxygen
      alone under identical conditions. Fifteen minutes after completion of
      anaesthesia, control and experimental groups were given 1 x 10(5) B16 melanoma
      cells intravenously. After 21 days, all animals were autopsied, and the
      metastatic nodules in their lungs were counted. The difference in the numbers of
      metastatic nodules between control and experimental groups of animals was
      analyzed for significance by the Mann Whitney "U test". RESULTS: More metastases
      were observed in the animals exposed to halothane (37.28 +/- 5.08, P < 0.0001),
      or isoflurane anaesthesia (28.24 +/- 4.07, P < 0.0014) than in the control
      animals (12.22 +/- 1.52). CONCLUSION: Exposure to halothane or isoflurane
      anaesthesia increased the number of pulmonary metastases in C57B1 mice compared
      with the control groups but there was no difference in metastases among animals
      treated with halothane or isoflurane.

PMID- 8988832
TI  - Dose-response of flurbiprofen on postoperative pain and emesis after paediatric
      strabismus surgery.
AB  - PURPOSE: Intravenous flurbiprofen, a non-steroidal antiinflammatory drug (NSAID),
      has been used recently for postoperative pain relief in adults. The drug is also
      likely to have antiemetic property. The present study was undertaken to
      investigate the effect of flurbiprofen on postoperative pain and emesis in
      children undergoing strabismus surgery, which is well known to produce
      postoperative nausea and vomiting. METHODS: In a prospective, randomised,
      controlled clinical trial, 90 children aged 2-11 yr received saline (control),
      flurbiprofen 0.5 mg.kg-1, or flurbiprofen 1 mg.kg-1. Saline and flurbiprofen were
      administered i.v. immediately after induction of anaesthesia. Anaesthesia was
      induced and maintained with sevoflurane and nitrous oxide in oxygen.
      Postoperative pain was assessed by a blinded observer using an objective pain
      scale (OPS). No opioids or antiemetics were administered throughout the study.
      The incidence and frequency of vomiting were compared among groups. RESULTS:
      Flurbiprofen 1 mg.kg-1 provided lower OPS (highest) scores during the eight hours
      after surgery and a reduced requirement for postoperative supplementary analgesic
      (diclofenac suppository) compared with the other two regimens. The two doses of
      flurbiprofen failed to decrease the incidence and frequency of vomiting.
      CONCLUSION: These data suggest that preoperative flurbiprofen 1 mg.kg-1 iv is a
      simple and effective approach to postoperative pain relief but not to the
      prevention of emesis following paediatric strabismus surgery.

PMID- 8988833
TI  - Diltiazem and vecuronium: neuromuscular and cardiovascular effects.

PMID- 8988834
TI  - Using continuous pressure monitoring to aid central vein cannulation.

PMID- 8988835
TI  - Intravenous anaesthesia and leukocytes.

PMID- 8988836
TI  - Placement of double-lumen tubes with a stylet.

PMID- 8988837
TI  - Preventive not pre-emptive analgesia with piroxicam.

PMID- 8988838
TI  - Inhibition of esophageal cancer proliferation by adenovirally mediated delivery
      of p16INK4.
AB  - We have been investigating the molecular basis of esophageal carcinogenesis in an
      attempt to develop gene therapy of established esophageal cancers and
      premalignant esophageal lesions. In this report we demonstrate the efficacy of
      adenovirally mediated p16 gene replacement in esophageal squamous cell cancers.
      Adenoviral p16 efficiently transduced epidermoid cancer cells containing p16
      mutations, and expression of exogenous p16 in these cells correlated with G1 cell
      cycle arrest and profound growth inhibition. No effects were observed in
      esophageal adenocarcinoma cells due to extremely poor transduction of these cells
      by adenovirus. These results may have implications regarding the design of
      clinical trials using p16 gene replacement strategies for intervention in
      esophageal cancers.

PMID- 8988839
TI  - Antibody-mediated gene delivery for B-cell lymphoma in vitro.
AB  - The targeted introduction of therapeutic genes into malignant cells based on
      receptor mediated endocytosis of ligand-DNA conjugates recently was established
      as a transfection system and provides a promising strategy for cancer therapy.
      Antiidiotype antibodies could be of particular interest for this approach because
      their immunoglobulin receptor idiotypes represent highly specific tumor markers.
      Their safe and specific applicability in vivo, alone or as immunotoxins, has been
      proven in clinical trials for passive immunotherapy and vaccination strategies.
      For these reasons we have explored the utility of antiidiotype antibodies for
      gene delivery systems using the reporter genes beta-galactosidase and luciferase.
      Two monoclonal antibodies, SIC5 and 5D10, specific for B-lymphoma cell lines,
      which represent models for murine plasmacytoma (38C13) and human non-Hodgkin's
      lymphoma (SU-DHL-4) have been covalently linked to polylysine via the
      heterobifunctional cross-linker SPDP. Highly efficient uptake and internalization
      of the immunoconjugates have been shown by fluorescence microscopy and
      fluorescence-activated cell sorting (FACS) analysis. Successful transfections
      have been shown at the RNA and the reporter gene level (beta-galactosidase,
      luciferase) using different promoter/enhancer systems. Beta-galactosidase
      activity was detected by flow cytometry (FACS-gal) analysis for both cell lines,
      and SU-DHL-4 cells showed significant luciferase activity.

PMID- 8988840
TI  - Expression of costimulatory molecules: B7 and ICAM up-regulation after treatment
      with a suicide gene.
AB  - The herpes simplex virus thymidine kinase gene (HSV-TK) in combination with
      ganciclovir (GCV), is currently being used in gene therapy-based clinical trials
      for cancer treatment. Its therapeutic effect is based on a "bystander effect"
      whereby HSV-TK gene-modified tumor cells are toxic to nearby unmodified tumor
      cells when exposed to the antiviral drug GCV. We have recently hypothesized that
      the in vivo mechanism of this bystander effect is due to alterations in the tumor
      microenvironment in response to release of cytokines and an infiltration of
      leukocytes after treatment with HSV-TK gene-modified tumor cells and GCV, which
      results in tumor regression. Expression of B7, a recently identified
      costimulatory molecule that is important for T-cell stimulation, has been shown
      to be modulated by stimulatory cytokines interferon-gamma, tumor necrosis factor
      alpha, and inhibited by interleukin-10. In the present study, we investigated
      whether the cytokines released after HSV-TK and GCV treatment could include the
      expression of the costimulatory molecules B7-1 and B7-2 and the adhesion molecule
      (ICAM)-1 in the tumor. Furthermore, we investigated whether this altered
      environment affected the antitumor properties of host lymphocytes. An in vitro
      model was developed to establish the effects of HSV-TK gene-modified tumor cells
      and GCV on tumor infiltrating cells. The murine macrophage cell line (IC21) was
      exposed to either supernatants or cell lysates collected from a mixture of HSV-TK
      transduced (KBALB-STK) and non-transduced (KBALB) murine fibrosarcoma tumor cells
      previously exposed to GCV (experimental). Immunohistochemical analysis showed a
      significant expression (P < .0001) of B7-1 and B7-2 post exposure of IC21 cells
      to either supernatant or lysate. In contrast, the level of expression in IC21
      cells exposed to the control lysate or supernatant remained unchanged for B7-1
      and B7-2. In vivo analysis for B7-1 and B7-2 expression by immunohistochemistry
      in tumor tissues from experimental mice receiving HSV-TK gene-modified tumor
      cells and GCV treatment showed a significant expression of B7.1 (35%, P < .0001)
      and B7.2 (38.2%, P < .0001) on tumor-infiltrating mononuclear cells. In contrast,
      tumor-bearing control animals showed low levels of B7-2 expression (5.8%),
      whereas B7-1 was undetectable, as confirmed by reverse-transcriptase polymerase
      chain reaction. In addition, a significant up-regulation of ICAM expression (50%)
      on tumor tissues was observed in the experimental group (P = .0317) as compared
      with the control group (25%). Furthermore, T cells isolated from experimental
      mice showed a significant in vitro proliferative response (p = .0202) when
      exposed to syngeneic tumor cells as compared with the control group. These data
      demonstrated that the use of HSV-TK gene-modified tumor cells and GCV as a
      suicide gene in the treatment of an intraperitoneal tumor resulted in the
      expression of the B7 costimulatory molecules and ICAM-1 adhesion molecule and
      enhanced proliferative response of host T cells. These findings help to
      understand the mechanism of tumor cell killing in vivo using HSV-TK gene-modified
      tumor cells.

PMID- 8988841
TI  - Liposomal delivery of the herpes simplex virus thymidine kinase gene in glioma:
      improvement of cell sensitization to ganciclovir.
AB  - In this study, we investigated whether the regulation and the copy number of the
      herpes simplex virus thymidine kinase (HSVtk) gene increased the sensitization to
      ganciclovir (GCV) of glioma cell lines (Rat C6 and human U118-MG) using liposome
      mediated gene transfer. Three recombinant plasmids carrying the HSVtk gene driven
      by the thymidine kinase promoter in single (pAGo) and double copy (pYED) or by
      the human cytomegalovirus promoter (pCMVtk) were used for the transfection. The
      DNA delivery was optimized by screening a panel of cationic liposomes using Lac-Z
      and luciferase as reporter genes. The efficiency of transfection reached 33% to
      36% in vitro but only 18.6% in vivo after an intratumoral injection of DNA
      liposome complexes. Moreover, after transfection of the three plasmids, the cell
      killing effect of GCV was evaluated. A significant enhancement (four- to
      fivefold) of the cell sensitivity to GCV was shown in pCMVtk and pYED as compared
      with pAGo-transfected cells in both cell lines. According to the plasmid, the
      effect of the HSVtk/GCV system was confirmed by in vivo experiments and was
      objectified by a higher tumor weight reduction with pCMVtk (49%) than pAGo (27%).
      From these results, we conclude that (1) the gene transfer can be achieved by
      cationic liposomes both in vitro and in vivo and that (2) using this type of
      vector, the antitumor effect of the HSVtk/GCV system could be potentiated by the
      up-regulation of HSVtk gene duplication.

PMID- 8988842
TI  - Participation of c-met in the progression of human gastric cancers: anti-c-met
      oligonucleotides inhibit proliferation or invasiveness of gastric cancer cells.
AB  - The protooncogene c-met encodes the receptor for hepatocyte growth factor (HGF),
      a potent epithelial cell mitogen with scattering activity. In this study, we
      first screened c-met expression in human gastric carcinomas. Twenty-eight of 154
      tumors (18%) were positively stained for MET proteins. The incidence of c-met
      expression increased with higher histopathological stages of the cancer. Second,
      we examined functional roles of c-met in cultured gastric carcinoma cells, using
      an antisense strategy. Cell lines used were MKN-45, TMK-1, and MKN-28. Among
      them, MKN-45 cells exhibited the highest c-met expression and grew in response to
      HGF, whereas TMK-1 cells had an ability to invade in an HGF-dependent manner.
      When antisense oligodeoxyribonucleotides complementary to c-met messenger RNA
      (mRNA) were administered to the culture medium, the content of MET protein was
      selectively decreased in either MKN-45 or TMK-1 cells, indicating that the
      antisense molecules did inhibit the translation of c-met mRNA. The growth of MKN
      45 cells was markedly inhibited by the antisense c-met oligonucleotides in a dose
      dependent manner, but not by sense or scrambled controls. The antisense
      oligonucleotides also effectively inhibited the migration of TMK-1 cells. These
      results indicate that c-met gene products may be causally related to the
      proliferation or invasion of gastric cancer cells, and that antisense c-met DNA
      has the potential to help circumvent the progression of gastric cancers.

PMID- 8988843
TI  - The drug verapamil inhibits bystander killing but not cell suicide in thymidine
      kinase-ganciclovir prodrug-activated gene therapy.
AB  - The bystander effect, in which unmodified cells are killed as the result of
      enzyme-prodrug activation in genetically modified neighboring cells, amplifies
      the suicide response in a tumor in which only a fraction of the cells are
      targeted. The drug verapamil (VRP), a calcium channel antagonist that is also
      used to counteract the multidrug resistance of tumor cells, is shown to inhibit
      the bystander effect by herpes simplex virus thymidine kinase (HSVtk) enzyme
      prodrug therapy with ganciclovir by protecting beta geo marked bystander cells in
      both in vitro coculture assays and in an in vivo animal tumor model. VRP had no
      stimulatory or inhibitory effect on the proliferation of CT 26 cells, their
      tumorigenicity, or prodrug-activated cell death produced by the action of the
      HSVtk gene. The kinetics of the protection afforded by VRP was time dependent
      with respect to the time of addition of the prodrug, and protection was
      ineffective when added two or more days after prodrug administration.

PMID- 8988844
TI  - The immunology of domestic animals: its present and future.
AB  - Veterinary immunology, defined as the immunology of domestic and wild animals
      having economical or sentimental value to man, provides both practical knowledge
      that is useful to animal husbandry, and new insights into fundamental immunology.
      Defining new immunologically based diagnostic tools and immunotherapeutic
      approaches, including vaccine strategies, obviously still represents important
      applied objectives. Resistance of domestic animals to disease might also be
      improved through genetic selection of animals for immunological traits. New
      contributions to fundamental immunology will arise from so-called 'Immunological
      opportunities in farm animals' (M. Parkhouse) such as: the ileal Peyer's patch of
      large animals as an accessible model for studying B cell differentiation; the
      significance of a high number of gamma delta T cells in ungulates and of double
      positive CD4+ CD8+ T cells; the possible manipulation of the immune system at a
      regional level in the living animal by cannulating lymphatic vessels; the use of
      spontaneous immunodeficiency or autoimmune diseases of animals as models for
      human clinical research. The fulfillment of these objectives benefits from the
      flow of information and communications among immunologists working on domestic
      animals. In addition to national specialized groups, the Veterinary Immunology
      Committee of the International Union of Immunological Societies (VIC-IUIS) was
      created to facilitate communication on veterinary immunology; to establish
      'official' links between veterinary immunology and the rest of the immunologists'
      community; and to support the organization of international workshops on domestic
      animal immunological reagents.

PMID- 8988845
TI  - The VH and CH immunoglobulin genes of swine: implications for repertoire
      development.
AB  - Swine have the largest number of IgG subclass genes of all species so far studied
      but have a single gene for IgA which occurs in two allelic forms that differ in
      hinge length. Swine also have constant region genes for C mu and C epsilon, but
      lack a gene homologous to that which encodes IgD in rodents and primates, despite
      the otherwise high degree of sequence similarity of all other swine CH genes with
      those of humans. Swine have < 20 VH genes, a single JH and perhaps a limited
      number of DH segments. Newborn piglets show preferential VH and DH usage and may
      use gene conversion as a mechanism for expanding their antibody repertoire.
      Despite the close similarity of their Ig gene sequences to humans, swine belong
      to the group of animals that includes rabbits, chickens and cattle when
      classified on the basis of B cell development. This group, unlike rodents and
      humans, have a single VH family, use hindgut follicles early in life (rather than
      bone marrow throughout life) to diversify their antibody repertoire and probably
      all use gene conversion. It is proposed that IgD may serve a function in
      repertoire development in rodents and humans which is unnecessary in the chicken
      lagomorph-artiodactyl group. The diversity of immunoglobulins and immunoglobulin
      genes among species justifies the quest of veterinary immunologists to define the
      system for their species of interest rather than making extrapolations from mouse
      and human immune systems.

PMID- 8988846
TI  - T cell cytokines and disease prevention.
AB  - Until recently, work on cytokines has been dominated by the use of murine or
      human molecules. In the last 5 years we have seen a rapid expansion in the
      production of bovine, ovine and porcine cytokine reagents. cDNA clones,
      recombinant proteins and monoclonal antibody probes are not available for a wide
      variety of cytokines from veterinary species. One of the most interesting recent
      proposals in immunology has been the division of T helper cells into two classes.
      Th1 cells have been characterised by the production of gamma-interferon,
      interleukin (IL)-2, tumour necrosis factor-beta (lymphotoxin-alpha) and the
      ability to mediate delayed-type hypersensitivity responses, and Th2 cells by
      their production of IL-4, IL-5, IL-6 and IL-10 and the ability to stimulate
      production of mast cells, eosinophils and IgE. An important issue for us is to
      determine whether polarisation of T helper cells to Th1 or Th2 occurs in
      veterinary species. This paper will attempt to review the status of the Th1 and
      Th2 debate for sheep, cattle and pigs. It will also discuss the potential for the
      use of cytokines in modulating the type of immune response following vaccination.
      By incorporation of particular cytokines into vaccine formulations or the
      inhibition of production of specific cytokines it may be possible to redirect the
      nature of the immune response to a particular antigen.

PMID- 8988848
TI  - Veterinary cytokine database.

PMID- 8988847
TI  - Inflammatory cytokines in animal health and disease.
AB  - Inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL
      1), IL-6 and IL-8, are rapidly induced early in a disease or injury process. They
      mediate and modulate myriad healing processes but, if overexpressed, may
      exacerbate the severity of a disease condition. In order to test this concept and
      to establish a foundation for the role of inflammatory cytokines in the
      pathogenesis of gram-negative bacterial infections in the respiratory tract of
      animals, the patterns of inflammatory cytokine expression were determined in
      experimental porcine pleuropneumonia. We observed that IL-1 and IL-6, but not
      TNF, were rapidly and dramatically elevated in the lavage fluid of the lung
      within 24 h of infection. The increased levels of IL-1 might contribute to
      increased severity of disease, but elevated IL-6 levels were consistent with a
      protective acute phase response. Additional studies were performed to examine the
      hypothesis that IL-4 expression later in infection might be involved in turning
      off the inflammatory response and promoting an antigen-specific humoral immune
      response. Interleukin-4 efficiently suppressed inflammatory cytokine production
      in alveolar macrophages. Its expression was induced in peripheral blood
      mononuclear cells by TNF, IL-4, and by reexposure to a specific antigen. To
      obtain the maximum amount of information on the role of inflammatory cytokines in
      animals of veterinary significance it will be useful to perform studies in
      species such that evolutionary relatedness will allow widespread application of
      the findings. Furthermore, the variety of molecules involved in inflammatory
      cytokine regulation will require much more extensive investigations of the
      relevant enzymes, inhibitors and receptors in veterinary species. Finally, the
      complexity and redundancy of immune defenses in animals mean that attempts to
      modulate health status through manipulation of inflammatory cytokines must be
      performed with caution and that a multiplicity of processes will be affected.

PMID- 8988849
TI  - Differentiation of B cells in the bovine. Role of cytokines in immunoglobulin
      isotype expression.
AB  - Cytokines such as IFN-gamma, IL-4 and TGF-beta, are known to regulate Ig class
      switching by positively or negatively regulating germline CH transcription in the
      mouse and human. Here we show at the protein level that similar regulatory
      mechanisms are in place in the bovine using various modes of B cell activation
      and cytokine combinations. Using antigen-receptor cross-linkage or mitogen
      (pokeweed mitogen) costimulation, we demonstrate that recombinant bovine IL-4
      upregulates the expression of IgM, IgG1 and IgE in vitro. Upregulation of IgG1
      and IgE production by rboIL-4 is inhibited in a dose-dependent manner by the
      addition or rboIFN-gamma to the cultures. Using similar methodologies, we have
      also investigated the effects of TGB-beta on IgA production in the presence or
      absence of various cofactors including IL-10 and IL-2. We find that TGF-beta will
      not solely upregulate IgA production from noncommitted precursors (sIgM+) in
      coculture with mitogen or with formalin fixed Staphylococcus cowan Strain I
      (SAC), but does have positive effects on IgA production in the presence of both
      IL-2 and IL-10. These observations suggest that different modes of T-independent
      costimulation using classical B cell activators does not result in differential
      IgG subisotype or IgE production by bovine B cells in the presence of cytokines.
      Together these results suggest that individual cytokines regulate isotype
      expression in cattle.

PMID- 8988850
TI  - Early ontogeny of immune cells and their functions in the fetal pig.
AB  - The origin of immune cells and their products have been studied in the prenatal
      period in miniature pigs. Macrophages were first detected on day 25, and
      myelocytes and lymphoid cells by day 28. Membrane antigens SLA-DR and CD45 were
      found by day 22, membrane molecules MG-7, 8/1, CD1, CD2 and 74-22 by day 28,
      Gamma/delta T cells were found initially in extrathymic sites (in the liver). The
      first gamma/delta T cells were detected as early as 40 days of gestation. The
      expression of fibronectin, Thy-1 and its message, Ig isotypes and the first
      induction of IFN alpha were described.

PMID- 8988851
TI  - In vivo depletion of T-cells and cytokines during primary exposure of sheep to
      parasites.
AB  - This study examined the role of CD8+ and WC1+ T-cells and of interferon (IFN)
      gamma in the development of protective immunity against infection with the
      enteric nematode parasite Trichostrongylus colubriformis in sheep. Monoclonal
      antibodies (mAb) were administered during induction of the immune response to
      deplete or neutralise these components. Protection against the primary and
      challenge infections was assessed by faecal egg count and total worm count.
      Prolonged administration of mAb recognising IFN-gamma and CD8 resulted in
      significantly increased protection during the 6 week primary infection and
      following challenge. CD8+ cells were depleted from blood but not from intestinal
      mucosa. After injection of mAb (CC15) recognising the surface antigen WC1, WC1+
      and Tcr gamma delta + cells were depleted from blood but not markedly from
      enteric mucosa, and protection against challenge, although variable, was
      increased by up to 88%. It appears that CD8+ and WC1+/gamma delta+ cells and IFN
      gamma all retard the potential development of naturally acquired immunity against
      the parasite.

PMID- 8988852
TI  - Constitutive and inflammatory lymphocyte trafficking.
AB  - Here we provide a brief overview of lymphocyte trafficking with particular
      emphasis on the current state of knowledge in the pig. We discuss how the
      emphasis of research has changed since early studies in the 1960s and outline the
      current hypothesis of a multistep cascade for lymphocyte migration through
      specialized endothelia. During the last several years our research has focused
      mainly on lymphocyte migration in vivo. The inbred Babraham herd of MHC
      homozygous Large White pigs has allowed study of entry of either labelled (FITC
      or 51Cr) or unlabelled CD45 allotype-different donor lymphocytes and their
      subsets into various lymphoid, non-lymphoid and inflammatory tissues. The
      findings are considered under three different categories. Firstly, constitutive
      lymphocyte entry via 'high endothelial venules' (HEV-mediated), secondly, non-HEV
      mediated lymphocyte homing and thirdly, lymphocyte entry into several models of
      inflammation with particular reference to the role of E-selectin. These findings
      demonstrate and underline the complexity and heterogeneity of lymphocyte homing,
      both at the whole population and subset level and yet, whilst a major step
      forward, the current hypotheses are perhaps too simple to explain much of this
      heterogeneity.

PMID- 8988853
TI  - gamma/delta T cell/endothelial cell interactions.
AB  - Ruminant gamma/delta T cells exhibit unique patterns of tissue- and inflammation
      specific recruitment. Studies of other cells, such as alpha/beta T cells and even
      neutrophils, have clearly shown that interactions with the vascular endothelium
      regulate the entry of these cells into tissues. The leukocyte/endothelial cell
      interaction is a dynamic event that occurs under considerable shear force
      associated with blood flow, and it involves a variety of adhesion molecules
      expressed by both the leukocyte and endothelium. We have begun a systematic
      analysis of gamma/delta T cell interactions with endothelial and other cells in
      novel in vitro assays that reflect blood flow to gain insight into the molecular
      basis of the selective recruitment of these lymphocytes to epithelial-associated
      tissues and sites of inflammation. We have found that bovine gamma/delta T cells
      in newborns predominantly use the selectin family of leukocyte and vascular
      adhesion proteins to interact with endothelial cells. This is in direct contrast
      to other lymphocytes, such as alpha/beta T cells, which predominantly interact
      with selectins only after conversion to a memory cell phenotype. Our analyses of
      gamma/delta T cell-selectin interactions will be summarized.

PMID- 8988854
TI  - Alternative pathway of complement in ruminants: role in infection.
AB  - Besides being initiated by antigen-antibody complexes, the classical pathway also
      can be activated by two innate mechanisms: (1) A family of proteins called
      collectins, which resemble C1q, bypass the activation of C1q. (2) Acute phase
      proteins, belonging to the family of pentraxins, activate the classical pathway
      by binding to C1q. The term 'alternative' complement pathway is a misnomer. This
      system is a primary primitive immune mechanism. It is phylogenetically older than
      the classical pathway. Contrary to the classical pathway, it does not require
      development of a specific immune response before getting into action. It acts
      within minutes after the microorganism has entered the body. The alternative
      pathway is continually activated at a low controlled rate but amplified by the
      surface of intruding microorganisms. It has the capacity to distinguish between
      self and non-self. Many nonpathogenic microorganisms are killed by the
      alternative pathway of complement. Pathogens have developed evasion mechanisms to
      escape the killing effect of this pathway. The kinetics of the activation of the
      alternative pathway of ruminants differs from that of mouse and man. The
      difference might be mediated by conglutinin.

PMID- 8988855
TI  - NK-lysin, structure and function of a novel effector molecule of porcine T and NK
      cells.
AB  - NK-lysin (NKL), a 78-residue antimicrobial peptide, was isolated from pig small
      intestine. Standard methods identified the peptide as basic, with six half
      cystine residues in three intrachain disulphide bonds. The sequence showed 33%
      identity with a part of a putative gene product (NKG5) from activated T and NK
      cells, NK-lysin showed antibacterial activity against Escherichia coli and
      Bacillus megaterium and marked lytic activity against YAC-1, a NK sensitive
      tumour cell line, while sheep red blood cells were unaffected. The cDNA clone
      corresponding to NK-lysin has been characterized. We have also analyzed the cell
      and tissue specific expression and the induction of the gene. A lymphocyte
      fraction enriched in T and NK cells, stimulated by human interleukin-2 (IL-2),
      showed a 30-fold increase of the NKL transcript. NK-lysin specific mRNA is also
      detectable in spleen, bone marrow and colon. Immunostaining showed NKL to be
      present in different types of lymphocytes. Our results strongly suggest that NK
      lysin is involved in the inducible cytotoxicity of T and NK cells.

PMID- 8988856
TI  - PR-39, a proline-rich peptide antibiotic from pig, and FALL-39, a tentative human
      counterpart.
AB  - The peptide antibiotic PR-39 was originally isolated from the upper part of pig
      intestine. It has antibacterial activity against Gram negative bacteria at
      concentrations comparable with tetracycline. Studies of the mechanism of action
      showed that PR-39 inhibits both DNA and protein synthesis. Recently, PR-39 was
      found in wound fluid and was shown to have inductive activity on matrix
      components as part of the wound repair process. We have now sequenced the
      complete gene and possible mediators of its expression will be discussed. Our
      attempts to characterize the human counterpart of PR-39 by probing for the well
      conserved prepro-part led to a different peptide antibiotic. A clone containing
      the coding information for this new peptide was isolated from a human bone marrow
      cDNA library. The putative human peptide antibiotic was designated FALL-39 after
      the first four residues and the total number of residues. All human peptide
      antibiotics previously isolated (or predicted) belong to the defensin family with
      three disulfide bridges, while FALL-39 lacks cysteine. The clone for the prepro
      FALL-39 encodes a cathelin-like precursor protein with 170 amino acid residues.
      We have postulated a dibasic processing site for the mature FALL-39 and
      chemically synthesized the peptide. In the presence of the basal medium E,
      synthetic FALL-39 was highly active against Escherichia coli D21 and Bacillus
      megaterium Bm11. Residues 13-34 in FALL-39 can be predicted to form a perfect
      amphipatic helix and CD spectra showed that medium E induced 30% helix formation
      in FALL-39. By Northern blot analyses the transcript was located in bone marrow
      and testis. The structure of the gene and the chromosomal location is under
      investigation.

PMID- 8988857
TI  - Fish immunology: the utility of immortalized lymphoid cells--a mini review.
AB  - Long term cell lines can be readily established at high frequency with PBLs from
      normal channel catfish. Depending upon the mode of stimulation, morphologically
      and functionally distinct catfish lymphoid cell lines resembling B cells, T cells
      and monocytes have been developed. These fish cell lines appear unique from their
      putative mammalian counterparts in that they are immortalized without the need
      for exogenous factors or overt attempts at transformation.

PMID- 8988858
TI  - The immune system of ectothermic vertebrates.
AB  - The adaptive immune system, as defined by T cell receptors, immunoglobulins, and
      the major histocompatibility complex (MHC), has been described definitively at
      the level of teleost fish. Cartilaginous fish, which display many of the
      hallmarks of such an adaptive system, nevertheless have several features of their
      responses that seem primitive. Data are presented suggesting that some adaptive
      mechanisms in cartilaginous fish, including MHC restriction and somatic
      diversification, are present to the same "degree' as compared to mammals, and
      that these animals may possess other molecules and functions previously
      overlooked. MHC linkage studies in amphibians suggest that the entire genetic
      complex, including class I, class II, and class III genes, arose early in the
      vertebrate line (at least 350 x 10(6) years ago) and has been maintained intact,
      at least for those genes involved in immunity. Studies of MHC in polyploid
      Xenopus have demonstrated that there is a maximal number of expressed MHC genes
      'permitted' to be expressed in any individual, regardless of the number of
      potential MHC-bearing chromosomes present in the species. A speculative
      hypothesis is presented on the origins of adaptive immunity based on ectothermic
      models.

PMID- 8988859
TI  - The Second International Swine CD Workshop.

PMID- 8988860
TI  - Summary report of the Second Equine Leucocyte Antigen Workshop.

PMID- 8988861
TI  - Mucosal immunity: an overview and studies of enteric and respiratory coronavirus
      infections in a swine model of enteric disease.
AB  - Based on the tenet of a common mucosal immune system, antigenic stimulation at
      one mucosal site results in the distribution of antigen-specific IgA precursor
      cells to distant mucosal sites. However, recent studies suggest that functional
      compartmentalization and limited reciprocity may exist within some components of
      the common mucosal immune system. Although oral immunization is often very
      effective in inducing immunity to respiratory pathogens, the converse
      (respiratory immunization to prevent enteric diseases) may not be as effective.
      To address this question and to study interactions between the bronchus
      associated (BALT) and gut-associated (GALT) lymphoid tissues related to
      protective immunity, we used as a model two antigenically related porcine
      coronaviruses which replicate primarily in the intestine (transmissible
      gastroenteritis virus, TGEV) or respiratory tract (porcine respiratory
      coronavirus, PRCV). The tissue distribution and magnitude of the antibody
      secreting cell (ASC) responses (measured by ELISPOT) and cell-mediated immune
      responses (measured by lymphoproliferative assays, LPA) coincided with the viral
      tissue tropisms. Immunization via GALT (gut infection with TGEV) elicited high
      numbers of IgA ASC and high LPA responses in GALT (gut lamina propria, LP or
      mesenteric lymph nodes, MLN), but lower responses in BALT (bronchial lymph nodes,
      BLN) and induced complete protection against enteric TGEV challenge. In contrast
      immunization via BALT (respiratory infection with PRCV) elicited systemic type
      responses (high numbers of IgG ASC in the BLN), but few ASC and low LPA responses
      in the gut LP or MLN and induced only partial protection against enteric TGEV
      challenge. Thus administration of vaccines intranasally may not be optimally
      effective for inducing intestinal immunity in contrast to the reported efficacy
      of oral vaccines for inducing respiratory immunity.

PMID- 8988862
TI  - Antigen presenting cells in the porcine gut.
AB  - It has long been known that mucosal responses are most effectively stimulated by
      local presentation of antigen but the mechanisms whereby the gut immune system is
      able to distinguish between potential pathogens and harmless dietary antigens are
      not clear. The gut immune system is capable of mounting both primary and
      secondary responses to potentially harmful antigens while avoiding the expression
      of damaging responses to harmless food proteins. Historically, most attention has
      focused on Peyer's patches and there is evidence of their role in the induction
      of both primary and secondary responses. Fed antigen can also be detected in the
      intestinal lamina propria (LP) and it has been shown that murine LP cells can
      stimulate allogenic mixed lymphocyte responses and present KLH to naive T cells.
      In contrast to guinea pigs, rodents and humans, pig intestinal epithelial cells
      do not express MHC Class II molecules, but they are present on a number of other
      cell types in the subepithelial LP. Amongst these are a significant proportion of
      non-professional APC including endothelial cells and eosinophils. Phenotypically
      pig LP T cells are a homogeneous population and the majority of CD4 T cells
      express the low molecular weight isoform of CD45. This is compatible with the
      suggestion that they are CD45RO-positive cells. A significant proportion of LP
      CD4 T cells are CD25 (IL-2R) positive, but following activation they secrete IL
      4, with little or no IL-2 production. Based upon these observations, we would
      conclude that the lamina propria is a unique immunological microenvironment, and
      suggest that it may be of significance not only in surveillance and the provision
      of help during rapid responses to recall antigens but also in the down-regulation
      of local responses to food-derived peptides.

PMID- 8988864
TI  - Workshop summary: local/mucosal immunity.

PMID- 8988863
TI  - Regulation of mucosal IgA responses in vivo: cytokines and adjuvants.
AB  - The predominance of IgA plasma cells at mucosal sites reflects a combination of
      the selective localisation and vigorous proliferation after extravasation of IgA
      plasma cell precursors. Experiments are described here which demonstrate that
      post-extravasation events leading to IgA precursor cell retention, proliferation
      and antibody secretion are under cytokine control. This has led to investigation
      of therapeutic interventions to modify cytokine availability to maximise mucosal
      vaccination responses and correct IgA deficiencies.

PMID- 8988865
TI  - The respiratory immune system of pigs.
AB  - Respiratory tract infections with bacteria like Actinobacillus pleuropneumoniae
      are extremely common in pigs and are of major veterinary relevance. The
      respiratory tract can be divided into the upper part, consisting of the nose,
      pharynx, larynx and trachea, and the lower part, consisting of the different
      parts of the lung. After bronchoscopy and bronchoalveolar lavage (BAL) had been
      established for pigs, interest grew in the unspecific parts of the immune system
      of the respiratory tract (such as macrophages, mast cells, the mucociliary
      function) and the specific immune system, consisting of the different lymphocyte
      subsets. In contrast to the rodent and human lung, the lung of the pig contains
      large numbers of intravascular macrophages with a high clearance capacity. The
      main focus of this paper is the localization, subset composition and
      quantification of lymphocytes in the pig lung: the intravascular and interstitial
      pool and the lymphocytes in the bronchial epithelium and lamina propria including
      bronchus-associated lymphoid tissue form the major compartments. In the BAL only
      a small proportion of nucleated cells are lymphocytes. The effects of age,
      antigen exposition, immunization and infection on the lymphocyte distribution in
      the pig lung are presented. In addition to veterinary aspects, the lung of pigs
      can also serve as a model for diseases in humans.

PMID- 8988866
TI  - Restricted B-cell responses to microbial challenge of the respiratory tract.
AB  - The local B-cell response in the respiratory tract to infectious challenge has
      been analyzed in pigs and calves using two techniques: flow cytometry and
      antibody secreting cell (ASC) probes. Pneumonia in pigs caused by experimental
      infection with Mycoplasma hyopneumoniae resulted in a 25-fold increase in the B
      cell population in BAL and lung parenchyma 28 days post infection. ASC probes
      revealed that the B-cell response of immune pigs to a large challenge infection
      was localized to lung parenchyma and tracheobronchal lymph nodes. Naive calves
      infected with Pasteurella multocida had a 5-fold increase in the B-cell blast
      population in lung parenchyma and BAL, and a greater than 60-fold increase in the
      draining lymph node at 9 days post infection. The ASC probes prepared post
      challenge from immune calves showed the response to be localized to the draining
      lymph nodes, with little response in lung parenchyma. A major finding was that
      ASC probes prepared from lung parenchyma and from pulmonary lymph nodes of both
      calves and pigs recognized a restricted range of bacterial antigens, particularly
      compared to the range of antigens recognized by concurrently circulating sera.
      The use of ASC probes demonstrates that there is a restricted B-cell repertoire
      in the respiratory tract.

PMID- 8988867
TI  - Identification of potential CTL epitopes of bovine RSV using allele-specific
      peptide motifs from bovine MHC class I molecules.
AB  - Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract
      infection in young infants and housed calves. Depletion of CD8+ lymphocytes from
      calves inhibited their ability to clear the virus from the nasopharynx and lungs.
      To study these cells further, a cytotoxic T lymphocyte (CTL) assay was
      established. CTL could be demonstrated in the peripheral blood of gnotobiotic
      calves 7-10 days post infection (p.i.) with RSV and in lungs 10 days p.i. This
      response was both MHC-restricted and virus-specific. Following separation of the
      lung lymphocytes by magnetic activated cell sorting, it was shown that the
      cytolytic activity was mediated by cells of the CD8+ phenotype. To identify
      epitopes recognised by bovine CTL, the consensus motifs from MHC class I alleles
      found in the herd at Compton were identified. cDNA libraries were constructed and
      screened for full length class I sequences. The isolated cDNA clones were then
      transfected into mouse P815 cells and the expressed product immunoprecipitated
      and matched with a serological specificity. The bovine MHC class I molecules were
      isolated from lysed transfected cells by affinity chromatography, using a
      monoclonal antibody specific for bovine MHC class I, and bound peptides were
      separated by reverse-phase HPLC. Analysis of the protein sequences of bovine RSV
      for the defined motifs has identified potential CTL epitopes.

PMID- 8988868
TI  - Immunobiology of pseudorabies (Aujeszky's disease).
AB  - Aujeszky's Disease (AD), a serious illness of pigs causing significant economic
      losses in the pig industry, is caused by Pseudorabies Virus (PrV). PrV belongs to
      the alphaherpesvirus subfamily of the herpesviruses with a double-stranded DNA
      genome in an enveloped capsid capable of encoding approximately 70 proteins. For
      disease control, vaccination with live and killed vaccines is performed.
      Recently, 'marked' vaccines have become available for use in eradication programs
      based on the differentiation between infected and vaccinated animals. PrV is also
      used as a viral vector for the development of multivalent vaccines. Despite the
      effectiveness of PrV vaccines, relatively little is known about the immune
      response against PrV infection. Several viral envelope glycoproteins have been
      shown to represent targets for antibody responses, and a number of isolated
      glycoproteins as well as genetically engineered proteins were able to elicit
      protective immunity. The nature of the cellular immune response is even less
      defined. Using viral mutants genetically engineered to lack specific antigens, it
      has been shown that glycoprotein C (gC) acts as a target for cytotoxic T
      lymphocytes, and gB, gC, gD, and gH appear to be involved in stimulation of in
      vitro proliferation of PBMC from immune animals. In addition, gB and gC have been
      implicated in recognition of infected cells by lymphokine-activated killer (LAK)
      cells. In summary, the data indicate a prominent role for viral envelope
      glycoproteins in eliciting humoral and cellular immune responses in the animal
      host. A complicating factor is the ability of PrV to productively infect cells of
      the hematopoietic system, which may impair immune responses and might also play a
      role in persistent or latent infection.

PMID- 8988869
TI  - Eimeria tenella infections in chickens: aspects of host-parasite: interaction.
AB  - Intestinal coccidiosis, caused by various species of Eimeria, has become an
      economically important disease of poultry and livestock throughout the world.
      Infection of chickens starts after ingestion of oocysts when sporozoites
      penetrate the epithelium of the villi. After passage through the lamina propria,
      they enter crypt epithelial cells where they undergo several rounds of asexual
      and sexual proliferation, thus forming merozoites and later, gametocytes. When
      macrogametes are fertilized by microgametes, oocysts are formed that are shed in
      the faeces. Nowadays, coccidiosis is prevented by anticoccidial drugs that are
      added to food, but the prolonged use of these drugs leads inevitably to the
      emergence of resistant Eimeria strains. During infection, there are three stages
      when the chicken immune system can inhibit parasitic development. The first is
      when the sporozoite searches for a site of penetration and binds to the
      epithelium. The second is when the sporozoite is in the villus epithelium amongst
      intra-epithelial leucocytes. The third is during its passage through the lamina
      propria to the crypt epithelium. To investigate this, the decisive factors in the
      induction and effector phase of immunity against coccidiosis have been
      investigated in situ. Our studies have revealed that three phenomena are
      responsible for immunity against Eimeria infections. First, the actual passage
      and presence of parasites in the lamina propria to induce immunity. Second, the
      sporozoite seems to be the most important parasite stage for immunity, and third,
      cytotoxic T cells are necessary to inhibit parasites.

PMID- 8988870
TI  - Genetic control of resistance to trypanosomiasis.
AB  - To map the genetic sources of trypanotolerance in mice, a linkage analysis of
      survival following trypanosome challenge was performed by selective genotyping in
      a large F2 population produced by crossing the resistant C57BL/6 and susceptible
      BALB/c inbred mouse lines. We report evidence of a chromosomal region of large
      effect, possibly comprising more than one resistance locus, on Chromosome 17; and
      of further loci on Chromosomes 1 and 5. Together, these genes can account for all
      of the difference between the mean parental phenotypes.

PMID- 8988871
TI  - Genetic control of resistance to helminths in sheep.
AB  - Uncertainties over the continued effectiveness of currently available
      anthelmintics and the massive costs associated with development of new drugs have
      provided an impetus to search for alternative measures to control
      gastrointestinal nematodes in sheep. One option is to exploit the genetically
      determined variability in resistance existing within host populations. A number
      of selection experiments, comprising divergent and control lines, have been
      initiated to investigate the nature of this genetic regulation. It was found that
      the heritability of worm-egg counts in faeces after infection ranges from 0.2 to
      0.4, indicating that worthwhile genetic gains can be achieved in commercial
      breeding programmes. Immune responses directed against parasites are under
      genetic control and appear to be the major factor responsible for the interline
      differences. Consequently, selection for increased resistance to gastrointestinal
      nematodes has resulted in an enhanced reactivity across a broad range of
      immunological functions (humoral, cellular and effector responses). These
      mechanistic studies have relevance to the development of vaccines and vaccination
      strategies, as well as for the application of phenotypic and genetic markers to
      measure resistance more accurately or to identify genetically resistant animals
      independently of infection.

PMID- 8988872
TI  - Cytokines and their inhibitors in orf virus infection.
AB  - The epitheliotropic parapoxvirus, orf virus, can repeatedly infect sheep skin. A
      specific immune response is generated as reinfections induce smaller lesions with
      quicker resolution times than primary lesions. Cyclosporin-A treatment abrogates
      this partial immunity. Cytokine mRNAs detected in lesion biopsies include the
      transcripts for IL-1 beta, IL-3 GM-CSF, TNF-alpha and, less reproducibly, IFN
      gamma. CD4+ T-cells predominate in afferent lymph draining the site of infection,
      and are the major source of GM-CSF and IFN-gamma. IL-1 beta and IL-8 are also
      detected. The orf virus genome contains a homologue of mammalian vascular
      endothelial growth factor that may enhance virulence and a vaccinia virus E3L
      like gene which may inhibit the anti-viral effect of the interferons. A GM-CSF
      inhibitory activity has also been discovered and has been 'chased' into a 10 kb
      DNA segment of the orf virus genome. These studies indicate that orf virus may
      temporarily avoid host immunity by a combination of acute, rapid infection and
      replication in the epidermis and by producing virulence factors that inhibit
      protective proteins of the host immune and inflammatory response.

PMID- 8988873
TI  - Local cell traffic and cytokine production associated with ectoparasite
      infection.
AB  - This paper reviews recent advances in our understanding of changes in local
      cellular traffic and cytokine synthesis that occur as a result of infection of
      sheep with the ectoparasite Lucilia cuprina. Changes in the cellular composition
      and cytokine profile of infected skin and draining afferent and efferent lymph
      were assessed using standard approaches and, in addition, a variety of techniques
      that have only recently become available as a result of advances in ruminant
      cytokine biology. These include cytokine-specific immunoassay, reverse
      transcription PCR (RT-PCR) and immunohistology. The initial acute inflammatory
      response was characterised by the infiltration of polymorphonuclear cells
      followed by selected lymphocyte subsets into discrete areas adjacent to the site
      of infection. Analysis of cytokine expression in skin prior to and following
      infection provided a molecular basis for the observed cellular events. Both
      cellular and molecular events within the skin were reflected within draining
      afferent lymph providing a basis for the conclusion that events within the skin
      (other than antigen uptake and transport) may influence events within the
      draining node and thus the outcome of the immune response to the parasite.
      Analysis of cellular and molecular changes in efferent lymph during infection
      suggested initiation of antigen-specific immunity.

PMID- 8988874
TI  - Expression of TNF alpha in arthritis caused by caprine arthritis encephalitis
      virus.
AB  - Goats infected with caprine arthritis encephalitis virus (CAEV) develop chronic
      arthritis sharing many features with human rheumatoid arthritis (RA). TNF is
      thought to be a key mediator contributing to the formation of the arthritic
      lesion in RA. We studied this cytokine in goats suffering from chronic arthritis.
      TNF alpha expressing cells were detected by in situ hybridization in synovial
      membranes of arthritic carpal joints. Expression of TNF alpha did not correlate
      with the degree of viral replication as assessed by in situ hybridization for
      viral RNA. In line with the lack of correlation between the degree of viral
      replication and TNF expression in vivo, we failed to detect increased cytokine
      RNA in goat macrophages infected with CAE virus in vitro and no TNF protein was
      found in culture supernatants. In addition, virus infection failed to prime goat
      macrophages for enhanced TNF expression in response to lipopolysaccharide. Taken
      together, these findings argue against a direct role of CAE virus in increasing
      the expression of TNF alpha in caprine arthritis.

PMID- 8988875
TI  - Detrimental effect of bovine leukemia virus (BLV) on the immunological state of
      cattle.
AB  - Bovine leukemia virus (BLV) is a retrovirus which seems to affect both the
      humoral and the cellular immune response. Cows affected by enzootic bovine
      leukemia (EBL) showed a reduction of IgM-producing cells in the spleen and lymph
      nodes. Experimentally infected calves had lower levels of secretory IgM and a
      decrease in T lymphocytes in the peripheral blood. The reduction in the amount of
      T cells was noticed mainly in cells bearing the CD4 markers. BLV-infected animals
      showed diminished responsiveness to newly encountered antigens. Cows naturally
      infected by BLV produced Igs with impaired structural or biological reactivity.
      The primary immune response was shown to be deficient in BLV-infected cows
      following vaccination with synthetic antigen. A marked shift in the proportion of
      PBL, especially of the CD5+ subset, was noticed. Peripheral blood mononuclear
      cells from BLV-infected cows secrete elevated levels of certain cytokines and
      contain increased levels of cytokine mRNA. High levels of cytokines are also
      found in the sera of BLV-infected cows compared to non-infected animals. A
      correlation was found between BLV infection and lack of spontaneous recovery from
      Trichophyton verrucosum infection. Moreover, some studies ascertained a
      significant association between the herd BLV infection status and disease
      incidence. The culling rate was higher and milk production lower in BLV-infected
      vs. BLV-free herds. It seems that BLV infection affects the immune system of a
      cow to such an extent that it ceases to be productive enough to be kept and, in
      most cases, the animal is culled before any symptoms of illness associated with
      persistent immunodeficiency become apparent.

PMID- 8988876
TI  - T lymphocyte mediated protection against facultative intracellular bacteria.
AB  - Acquired immunity against intracellular bacteria is T cell dependent. T cells
      play a major role in protection against intracellular bacteria, but bacterial
      antigens recognized by T cells have been studied less extensively than bacterial
      antigens recognized by B cells. Using T lymphocytes from animals immunized
      against Brucella abortus, we have screened a bacterial genomic library for genes
      encoding antigens recognized by T cells. Lymphocytes that proliferated to B.
      abortus proteins were characterized for phenotype and cytokine activity. Bovine
      and murine lymphocytes recognized common bacterial antigens and possessed similar
      cytokine profiles, suggesting an analogous immune response in these two animal
      species. In vivo protection afforded by a particular cell type is dependent on
      the bacterial antigens presented and mechanisms of antigen presentation. MHC
      class I and class II gene knockout animals infected with B. abortus have
      demonstrated that protection to B. abortus is especially dependent on CD8+ T
      cells. Knowing the cells required for protection, vaccines can be designed to
      elicit the protective subset of lymphocytes. Currently, we are testing several
      recombinant B. abortus proteins using different immunization strategies. Finally,
      bacterial genes activated following intracellular phagocytosis are being examined
      using a novel, reporter system adapted to B. abortus.

PMID- 8988877
TI  - Inducible nitric oxide synthase of macrophages. Present knowledge and evidence
      for species-specific regulation.
AB  - An important mechanism by which macrophages (M phi) halt the growth of and
      eliminate a broad array of intracellular pathogens is the production of nitric
      oxide (NO). NO generation is catalyzed by inducible nitric oxide synthase (iNOS)
      converting arginine into citrulline and NO. In murine M phi, iNOS activity is
      regulated largely at the transcriptional level. LPS and IFN-gamma induce iNOS, IL
      4 and TGF-beta down-regulate LPS or IFN-gamma induced iNOS. In human M phi, iNOS
      cannot be induced by conventional activating regimes in vitro. We studied iNOS
      induction in ruminant monocytes and M phi from various sources (bone marrow,
      alveolar lavage, peripheral blood) and found that there is a species-specific and
      differentiation stage-dependent pattern of iNOS regulation in vitro. Notably,
      cattle M phi and monocytes respond to distinct signals by iNOS expression. Goat
      monocytes and M phi resemble human, pig and rabbit M phi in that upon treatment
      with conventional activating stimuli, they express less iNOS than unstimulated
      murine or bovine M phi and fail to generate detectable amounts of nitrite and
      nitrate.

PMID- 8988878
TI  - Mucosal mast cells and the allergic response against nematode parasites.
AB  - IgE-mediated Type-I allergic reactions at nematode-infected mucosal surfaces are
      considered to have a direct protective function. The contribution of mucosal mast
      cells (MMC) to these mucosal allergic responses is reviewed. In addition to the T
      helper 2 cell-mediated regulation of MMC hyperplasia during nematode infection
      the kit ligand, stem cell factor (SCF), plays a key role in the early development
      of the MMC response. Studies in the mouse suggest that MMC protect against
      certain nematodes which enter the mucosa but not against lumen dwelling
      nematodes. The protective roles of MMC in other species, including sheep, are
      less certain and there is some evidence that MMC might enhance parasite
      fecundity. The measurement of MMC-specific granule chymases released
      systemically, and into the gut lumen, permits precise monitoring of mast cell
      activation and suggests that the secreted chymases may target epithelial
      junctional complex proteins, thereby causing increased mucosal permeability. The
      abundant intraepithelial MMC found in parasitised mucosa may, therefore, serve as
      epithelial gatekeepers permitting the translocation of plasma proteins onto the
      mucosal surface.

PMID- 8988879
TI  - Local TH1 and TH2 responses to parasitic infection in the intestine: regulation
      by IFN-gamma and IL-4.
AB  - Control of parasitic infections is dependent on the production of cytokines that
      activate mechanisms which limit invasion, reproduction or survival of the
      parasite. In contrast, conditions that induce inappropriate cytokine responses
      facilitate the spread of infection and ultimately exacerbate the level of
      disease. Measurement of local cytokine responses to different gastrointestinal
      parasites, such as the intracellular protozoan, Cryptosporidium parvum, and
      luminal dwelling nematodes like Nippostrongylus brasiliensis and Heligmosomoides
      polygyrus, reveal stereotype response patterns. In general, intracellular
      parasites stimulate type 1 responses where IFN-gamma is the predominant immune
      activator, while extracellular parasites stimulate type 2 responses where IL-4
      plays a prominent role in elevating humoral immune mechanisms. Cytokines alter
      cellular function and the milieu of the intestinal lumen to affect the outcome of
      an infection. The importance of a particular response during the course of an
      infection can be studied by selective enhancement with an excess of exogenous
      recombinant cytokine or cytokine antagonists. For example, exogenous IL-12
      enhances resistance to C.parvum, but suppresses the normally rapid cure of an
      infection with N. brasiliensis. Both mechanisms are dependent on expression of
      IFN-gamma. At the molecular level, exogenous IL-12 stimulates IFN-gamma
      production which elevates a protective type 1 response to C. parvum but converts
      the normally anti-worm type 2 response to a type 1 response that inappropriately
      regulates the infection. Alternatively, excess IL-4 plays a prominent role in
      modulating effector elements that change intestinal physiology to create a
      hostile environment for worm parasites. Exogenous IL-4 can cure chronic worm
      infection, while IL-4 antagonists interfere with protective responses to
      infection. These observations provide a paradigm for analysis of stereotype
      responses to different gastrointestinal parasites, and demonstrate how cytokine
      induced immune system-dependent and independent effector mechanisms can limit
      parasitic infection, while inappropriate cytokine responses can exacerbate the
      state of disease.

PMID- 8988880
TI  - Novel viral vaccines for livestock.
AB  - Recent advances in our understanding of virulence factors of viruses and the
      proteins or glycoproteins involved in inducing neutralizing antibodies or cell
      mediated immunity are forming the foundation for the development of a new
      generation of viral vaccines. Using bovine herpesvirus as an example, we have
      identified glycoproteins gB, gC, and gD as important targets for inducing
      neutralizing antibody responses, with gD being able to induce the highest
      neutralizing and cellular responses. For subunit vaccine development, the
      glycoproteins were produced in both prokaryotic and eukaryotic expression
      systems. Glycoproteins produced in eukaryotic systems were very effective in
      stimulating a broad range of immune responses in cattle. These glycoproteins were
      then formulated into effective vaccines that prevented both virus shedding and
      clinical disease. Herpesviruses also served as an excellent model for the
      identification and deletion of specific genes which lead to attenuation. In
      herpesviruses, two major classes of genes can be deleted. Class I includes
      glycoprotein genes that are nonessential for virus replication in vitro, and
      Class II includes genes involved in nucleic acid metabolism. these gene deleted
      regions can then be replaced with genes coding for protective antigens of other
      pathogens to develop multivalent vaccines in a single vector. Similar approaches
      are being used for other viruses including vaccinia virus and adenovirus.
      Finally, we introduced plasmids coding for protective antigens, gB, gC, and gD,
      into animals and developed immunity to these antigens. This approach has the
      potential to revolutionize vaccination regimes of the future.

PMID- 8988881
TI  - Nonrecombinant and recombinant avirulent Salmonella vaccines for poultry.
AB  - We have constructed and evaluated a live avirulent Salmonella typhimurium vaccine
      strain, attenuated by deletion (delta) mutations in genes for adenylate cyclase
      (cya) and the cAMP receptor protein (crp). Immunization of chicks can preclude
      Salmonella colonization and invasion of challenged vaccinated chickens when
      compared with the non vaccinated control. Immunization induces significant cross
      protective immunity against various Salmonella serotypes and protects laying hens
      from transmission of Salmonella in or on eggs following challenge with S.
      enteritidis or S. typhimurium. Immunization of chicks destined to be breeders and
      then with a booster immunization at 16-18 weeks of age leads to maternal transfer
      of immunity to chicks which then can be immunized either orally or by coarse
      spray to display an enhanced immunity to prevent infection of visceral organs by
      and shedding of Salmonella. The attenuated S. typhimurium vaccine can be
      genetically manipulated to express foreign antigens specified by cloned genes
      from other pathogens. Immunization with such recombinant vaccines not only
      induces immunity to Salmonella but to infection by the pathogen that supplied the
      genes specifying the protective antigens expressed by the recombinant vaccine.

PMID- 8988882
TI  - Novel adjuvants and vaccine delivery systems.
AB  - Conventionally the efficiency of an adjuvant is measured by the capacity to
      induce enhanced antibody serum titres and cell mediated immunity (CMI) to a given
      antigen. Nowadays the capacity of an adjuvant is also measured by the quality as
      well as the magnitude of the induced immune response, guided by the protective
      immune response required. Quality includes isotype and IgG subclass responses, T
      helper cell responses characterized by the cytokine profile and cytotoxic T cells
      (CTL). In the early phase of immunization some adjuvants influence the antigen
      administration and uptake by a so-called depot effect exemplified by aluminium
      hydroxide gel and oil adjuvants, which possibly is not as desired as alledged. A
      modern depot is exerted by slow release formulations continuously releasing the
      antigen over a period of time or by pulses at intervals aiming at 'single
      injection' vaccine. Great efforts are made to formulate efficient delivery
      formulations targeting the antigens from the site of administration, to draining
      lymph nodes or distant lymphatic tissue or to mucosal surfaces by parenteral or
      mucosal administrations. Nowadays, non-replicating carriers besides replicating
      vaccines are formulated to induce mucosal immune responses encompassing secretory
      IgA and CMI. Efforts to evoke immune responses on mucosal membranes distant from
      the site of administration have resulted mostly in little success. For a long
      time it was considered that CTL under the restriction of MHC Class I only could
      be evoked by replicating viruses or intracellular parasites. However, novel
      adjuvant delivery systems readily induce CTL by delivering the antigen to the APC
      resulting in intracellular transport to the cytosol for the MHC Class I
      presentation system, as well as to the endosomal pathway for the MHC Class II
      presentation.

PMID- 8988883
TI  - Workshop: veterinary immunology teaching.

PMID- 8988884
TI  - Induced abortion and the risk of breast cancer.
AB  - BACKGROUND: It has been hypothesized that an interrupted pregnancy might increase
      a woman's risk of breast cancer because breast cells could proliferate without
      the later protective effect of differentiation. METHODS: We established a
      population-based cohort with information on parity and vital status consisting of
      all Danish women born from April 1, 1935, through March 31, 1978. Through linkage
      with the National Registry of Induced Abortions, information on the number and
      dates of induced abortions among those women was combined with information on the
      gestational age of each aborted fetus. All new cases of breast cancer were
      identified through linkage with the Danish Cancer Registry. RESULTS: In the
      cohort of 1.5 million women (28.5 million person-years), we identified 370,715
      induced abortions among 280,965 women (2.7 million person-years) and 10,246 women
      with breast cancer. After adjustment for known risk factors, induced abortion was
      not associated with an increased risk of breast cancer (relative risk, 1.00; 95
      percent confidence interval, 0.94 to 1.06). No increases in risk were found in
      subgroups defined according to age at abortion, parity, time since abortion, or
      age at diagnosis of breast cancer. The relative risk of breast cancer increased
      with increasing gestational age of the fetus at the time of the most recent
      induced abortion: <7 weeks, 0.81 (95 percent confidence interval, 0.58 to 1.13);
      7 to 8 weeks, 1.01 (0.89 to 1.14); 9 to 10 weeks, 1.00 >12 weeks, 1.38 (1.00 to
      1.90) (reference category, 9 to 10 weeks). CONCLUSIONS: Induced abortions have no
      overall effect on the risk of breast cancer.

PMID- 8988885
TI  - A preliminary evaluation of a recombinant circumsporozoite protein vaccine
      against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group.
AB  - BACKGROUND: The candidate vaccines against malaria are poorly immunogenic and
      thus have been ineffective in preventing infection. We developed a vaccine based
      on the circumsporozoite protein of Plasmodium falciparum that incorporates
      adjuvants selected to enhance the immune response. METHODS: The antigen consists
      of a hybrid in which the circumsporozoite protein fused to hepatitis B surface
      antigen (HBsAg) is expressed together with unfused HBsAg. We evaluated three
      formulations of this antigen in an unblinded trial in 46 subjects who had never
      been exposed to malaria. RESULTS: Two of the vaccine formulations were highly
      immunogenic. Four subjects had adverse systemic reactions that may have resulted
      from the intensity of the immune response after the second dose, which led us to
      reduce the third dose. Twenty-two vaccinated subjects and six unimmunized
      controls underwent a challenge consisting of bites from mosquitoes infected with
      P. falciparum. Malaria developed in all six control subjects, seven of eight
      subjects who received vaccine 1, and five of seven subjects who received vaccine
      2. In contrast, only one of seven subjects who received vaccine 3 became infected
      (relative risk of infection, 0.14; 95 percent confidence interval, 0.02 to 0.88;
      P<0.005). CONCLUSIONS: A recombinant vaccine based on fusion of the
      circumsporozoite protein and HBsAg plus a potent adjuvant can protect against
      experimental challenge with P. falciparum sporozoites. After additional studies
      of protective immunity and the vaccination schedule, field trials are indicated
      for this new vaccine against P. falciparum malaria.

PMID- 8988886
TI  - Medical care costs and quality of life after randomization to coronary
      angioplasty or coronary bypass surgery. Bypass Angioplasty Revascularization
      Investigation (BARI) Investigators.
AB  - BACKGROUND: Randomized trials comparing coronary angioplasty with bypass surgery
      in patients with multivessel coronary disease have shown no significant
      differences in overall rates of death and myocardial infarction. We compared
      quality of life, employment, and medical care costs during five years of follow
      up among patients treated with angioplasty or bypass surgery. METHODS: A total of
      934 of the 1829 patients enrolled in the randomized Bypass Angioplasty
      Revascularization Investigation participated in this study. Detailed data on
      quality of life were collected annually, and economic data were collected
      quarterly. RESULTS: During the first three years of follow-up, functional-status
      scores on the Duke Activity Status Index, which measures the ability to perform
      common activities of daily living, improved more in patients assigned to surgery
      than in those assigned to angioplasty (P<0.05). Other measures of quality of life
      improved equally in both groups throughout the follow-up period. Patients in the
      angioplasty group returned to work five weeks sooner than did patients in the
      surgery group (P<0.001). The initial mean cost of angioplasty was 65 percent that
      of surgery ($21,113 vs. $32,347, P<0.001), but after five years the total medical
      cost of angioplasty was 95 percent that of surgery ($56,225 vs. $58,889), a
      difference of $2,664 (P = 0.047). The five-year cost of angioplasty was
      significantly lower than that of surgery among patients with two-vessel disease
      ($52,930 vs. $58,498, P<0.05), but not among patients with three-vessel disease
      ($60,918 vs. $59,430). After five years of follow-up, surgery had an overall cost
      effectiveness ratio of $26,117 per year of life added, but unacceptable ratios of
      $100,000 or more per year of life added could not be excluded (P=0.13). Surgery
      appeared particularly cost effective in treating diabetic patients because of
      their significantly improved survival. CONCLUSIONS: In patients with multivessel
      coronary disease, coronary-artery bypass surgery is associated with a better
      quality of life for three years than coronary angioplasty, after the initial
      morbidity caused by the procedure. Coronary angioplasty has a lower five-year
      cost than bypass surgery only in patients with two-vessel coronary disease.

PMID- 8988887
TI  - An outbreak of gastroenteritis and fever due to Listeria monocytogenes in milk.
AB  - BACKGROUND: After an outbreak of gastroenteritis and fever among persons who
      attended a picnic in Illinois, chocolate milk served at the picnic was found to
      be contaminated with Listeria monocytogenes. METHODS: In investigating this
      outbreak, we interviewed the people who attended the picnic about what they ate
      and their symptoms. Surveillance for invasive listeriosis was initiated in the
      states that receive milk from the implicated dairy. Stool and milk samples were
      cultured for L. monocytogenes. Serum samples were tested for IgG antibody to
      listeriolysin O. RESULTS: Forty-five persons had symptoms that met the case
      definition for illness due to L. monocytogenes, and cultures of stool from 11
      persons yielded the organism. Illness in the week after the picnic was associated
      with the consumption of chocolate milk. The most common symptoms were diarrhea
      (present in 79 percent of the cases) and fever (72 percent). Four persons were
      hospitalized. The median incubation period for infection was 20 hours (range, 9
      to 32), and persons who became ill had elevated levels of antibody to
      listeriolysin O. Isolates from stool specimens from patients who became ill after
      the picnic, from sterile sites in three additional patients identified by
      surveillance, from the implicated chocolate milk, and from a tank drain at the
      dairy were all serotype 1/2b and were indistinguishable on multilocus enzyme
      electrophoresis, ribotyping, and DNA macrorestriction analysis. CONCLUSIONS: L.
      monocytogenes is a cause of gastroenteritis with fever, and sporadic cases of
      invasive listeriosis may be due to unrecognized outbreaks caused by contaminated
      food.

PMID- 8988888
TI  - Proton-pump inhibition of gastric chloride secretion in congenital chloridorrhea.

PMID- 8988889
TI  - Images in clinical medicine. Bullous pemphigoid.

PMID- 8988890
TI  - Primary pulmonary hypertension.

PMID- 8988891
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 1-1997. A 23-year-old man with fulminant hepatorenal failure of
      uncertain cause.

PMID- 8988892
TI  - Abortion, breast cancer, and epidemiology.

PMID- 8988894
TI  - Listeria gastroenteritis--old syndrome, new pathogen.

PMID- 8988893
TI  - A malaria vaccine based on a sporozoite antigen.

PMID- 8988895
TI  - Health care reform stages a comeback in Massachusetts.

PMID- 8988896
TI  - Propagation of a human herpesvirus from AIDS-associated Kaposi's sarcoma.
AB  - BACKGROUND: Although unique DNA sequences related to gammaherpesviruses have been
      found in Kaposi's sarcoma lesions, it is uncertain whether this DNA encodes a
      virus that is able to reproduce. METHODS: We isolated and propagated a filterable
      agent whose DNA sequences were found to be identical to those of the Kaposi's
      sarcoma-associated herpesvirus (KSHV). We obtained early-passage spindle cells
      from skin lesions of patients with the acquired immunodeficiency syndrome (AIDS)
      who had Kaposi's sarcoma and cultured them with cells of the human embryonal
      kidney epithelial-cell line 293. We characterized the virus according to its
      effects on cellular morphology and viral replication and its appearance on
      electron microscopy. RESULTS: KSHV was cytotoxic to 293 cells and was detected by
      the polymerase chain reaction (PCR) in infected cells but not uninfected ones.
      Cytotoxicity and positive PCR signals were consistently maintained with viral
      titers of 1 million per milliliter, for about 20 serial infections of 293 cells.
      The viral copy number was relatively low (1 to 10 copies per cell). Viral
      replication was confirmed by Southern blot analysis of DNA isolated from the
      enriched nuclear fraction of infected cells and by a semiquantitative PCR using
      dilutions of the lysates of infected cells to detect the 233-bp viral DNA
      fragment originally described in association with Kaposi's lesions. Electron
      microscopy revealed herpesvirus-like particles in about 1 percent of cells from
      infected cultures, as compared with none in cells from uninfected cultures.
      CONCLUSIONS: A herpesvirus with DNA sequences identical to those of KSHV can be
      propagated from skin lesions of patients with AIDS-associated Kaposi's sarcoma.

PMID- 8988897
TI  - The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal
      surgery in Cushing's disease.
AB  - BACKGROUND: Irradiation of the pituitary is widely considered the most
      appropriate treatment for patients with Cushing's disease in whom transsphenoidal
      microsurgery has been unsuccessful. However, there is little information about
      the long-term efficacy of this treatment. METHODS: We used external pituitary
      radiation to treat 30 adult patients with persistent or recurrent Cushing's
      disease after unsuccessful transsphenoidal surgery. The mean (+/-SD) dose of
      radiation was 50+/-1 Gy. Pituitary and adrenal function was assessed every six
      months after radiation therapy. Remission was defined as the regression of
      symptoms and signs of Cushing's syndrome, normal urinary cortisol excretion, and
      a low plasma cortisol concentration in the morning after the administration of 1
      mg of dexamethasone at midnight. RESULTS: Twenty-five patients (83 percent) had
      remissions during a median follow-up of 42 months (range, 18 to 114). The
      remissions began 6 to 60 months after radiation therapy, but in most cases (22
      patients) remission occurred during the first 2 years. None of the 25 patients
      had a relapse of Cushing's disease after remission was achieved. There was no
      relation between the response to radiotherapy and sex, age, urinary cortisol
      excretion before radiotherapy, the interval between surgery and radiotherapy,
      whether a pituitary adenoma was found by pathological examination, or tumor size.
      Seventeen patients had a deficiency of growth hormone after radiation therapy, 10
      had a deficiency of gonadotropins, 4 had a deficiency of thyrotropin, and 1 had a
      deficiency of corticotropin. CONCLUSIONS: Pituitary irradiation is an effective
      and well-tolerated treatment for patients with Cushing's disease in whom
      transsphenoidal surgery is unsuccessful.

PMID- 8988898
TI  - Images in clinical medicine. Thoracoscopic clipping of patent ductus arteriosus.

PMID- 8988899
TI  - Melatonin in humans.

PMID- 8988900
TI  - Vaccines to prevent viral hepatitis.

PMID- 8988901
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 2-1997. A 38-year-old man with digital clubbing, low-grade fever,
      and a murmur.

PMID- 8988902
TI  - Prevention of atherosclerosis in coronary-artery bypass grafts.

PMID- 8988903
TI  - Propagating Kaposi's sarcoma-associated herpesvirus.

PMID- 8988904
TI  - Treatment, and retreatment, of Cushing's disease.

PMID- 8988905
TI  - Men, women, and health insurance.

PMID- 8988906
TI  - Comparison of ground-based and space flight energy expenditure and water turnover
      in middle-aged healthy male US astronauts.
AB  - Energy requirements during space flight are poorly defined because they depend on
      metabolic-balance studies, food disappearance, and dietary records. Water
      turnover has been estimated by balance methods only. The purpose of this study
      was to determine energy requirements and water turnover for short-term space
      flights (8-14 d). Subjects were 13 male astronauts aged 36-51 y with normal body
      mass indexes (BMIs). Total energy expenditure (TEE) was determined during both a
      ground-based period and space flight and compared with the World Health
      Organization (WHO) calculations of energy requirements and dietary intake. TEE
      was not different for the ground-based and the space-flight periods (12.40 +/-
      2.83 and 11.70 +/- 1.89 MJ/d, respectively), and the WHO calculation using the
      moderate activity correction was a good predictor of TEE during space flight.
      During the ground-based period, energy intake and TEE did not differ, but during
      space flight energy intake was significantly lower than TEE; body weight was also
      less at landing than before flight. Water turnover was lower during space flight
      than during the ground-based period (2.7 +/- 0.6 compared with 3.8 +/- 0.5 L/d),
      probably because of lower fluid intakes and perspiration loss during flight. This
      study confirmed that the WHO calculation can be used for male crew members'
      energy requirements during short space flights.

PMID- 8988907
TI  - Zinc supplementation reduced morbidity, but neither zinc nor iron supplementation
      affected growth or body composition of Mexican preschoolers.
AB  - In rural Mexico and in many developing countries micronutrient deficiencies,
      growth stunting, and morbidity from infectious diseases are highly prevalent in
      young children. We assessed the extent to which growth stunting could be reversed
      and the number of infectious disease episodes reduced by zinc and/or iron
      supplementation. In a double-blind, randomized community trial 219 Mexican
      preschoolers were supplemented with either 20 mg Zn as zinc methionine, 20 mg Fe
      as ferrous sulfate, 20 mg Zn + 20 mg Fe, or a placebo. After 12 mo, plasma zinc
      increased significantly in the two zinc-treated groups, and plasma ferritin was
      significantly higher in the two iron-treated groups. There was no effect of
      treatments on growth velocity or body composition. Children in both zinc
      supplemented groups had fewer episodes of disease (zinc alone, 3.9 +/- 0.3;
      zinc+iron, 3.7 +/- 0.4; placebo, 4.6 +/- 0.5; P < 0.03), including diarrhea (zinc
      alone, 0.7 +/- 0.1; zinc+iron, 0.8 +/- 0.1; placebo, 1.1 +/- 0.2; P < 0.01). Zinc
      and zinc+iron supplements reduced morbidity but had no effect on growth or body
      composition.

PMID- 8988909
TI  - Consumption of cow milk and egg by lactating women and the presence of beta
      lactoglobulin and ovalbumin in breast milk.
AB  - beta-Lactoglobulin and ovalbumin in mature human milk in healthy lactating
      Japanese women (n = 24) were determined by using an enzyme-linked immunosorbent
      assay. Subjects consumed > or = +200 mL cow milk/d for 1 wk before the sampling
      day and exactly 200 mL cow milk on the morning of the sampling day. beta
      Lactoglobulin was detected (> 0.1 microgram/L) in breast milk in 15 of the 24
      subjects (62.5%), with a maximum concentration of 16.5 micrograms/L. Ovalbumin
      was detected in only two subjects (8.3%) after the subjects followed their usual
      diet. beta-Lactoglobulin concentrations were low in the subjects whose cow milk
      consumption during the entire lactating period was low, even though all subjects
      consumed the same amount of cow milk before sampling. This result suggests that
      beta-lactoglobulin concentrations in breast milk are related to long-term
      consumption of cow milk. Amounts of food antigens in breast milk may be
      controlled by modifying the daily maternal diet.

PMID- 8988908
TI  - Nutritional status and cognitive functioning in a normally aging sample: a 6-y
      reassessment.
AB  - Associations between nutritional status and cognitive performance were examined
      in 137 elderly (aged 66-90 y) community residents. Participants were well
      educated, adequately nourished, and free of significant cognitive impairment.
      Performance on cognitive tests in 1986 was related to both past (1980) and
      concurrent (1986) nutritional status. Several significant associations (P < 0.05)
      were observed between cognition and concurrent vitamin status, including better
      abstraction performance with higher biochemical status and dietary intake of
      thiamine, riboflavin, niacin, and folate (rs = 0.19-0.29) and better visuospatial
      performance with higher plasma ascorbate (r = 0.22). Concurrent dietary protein
      in 1986 correlated significantly (rs = 0.25-0.26) with memory scores, and serum
      albumin or transferrin with memory, visuospatial, or abstraction scores (rs =
      0.18-0.22). Higher past intake of vitamins E, A, B-6, and B-12 was related to
      better performance on visuospatial recall and/or abstraction tests (rs = 0.19
      0.28). Use of self-selected vitamin supplements was associated with better
      performance on a difficult visuospatial test and an abstraction test. Although
      associations were relatively weak in this well-nourished and cognitively intact
      sample, the pattern of outcomes suggests some direction for further research on
      cognition-nutrition associations in aging.

PMID- 8988910
TI  - Postprandial changes in plasma and serum viscosity and plasma lipids and
      lipoproteins after an acute test meal.
AB  - The influence of a fat-rich test meal on postprandial changes in plasma viscosity
      and serum viscosity was assessed in 12 normolipidemic adults. After a 12-14-h
      fast, volunteers (five men and seven women aged 23-50 y) were challenged with a
      test milk shake containing 50 g fat/m2 body surface area (BSA). Plasma viscosity,
      serum viscosity, and plasma lipids and lipoproteins were assessed at 0, 2, 3, 4,
      and 6 h. Viscosity values were determined by using a Mettler Contraves LS-40
      rotational microviscometer. Postprandial changes in the study variables were
      assessed by area under the curve and included triacylglycerols (2.02 mmol/L),
      plasma viscosity (-0.10 mPa.s), and serum viscosity (-0.01 mPa.s). Peak plasma
      triacylglycerol concentrations were significantly greater than those observed at
      baseline (P = 0.0022). There were no significant changes in any other variable
      when fasting and peak values were compared. Peak plasma viscosity increased in
      three and decreased in two subjects with no changes in the remaining seven
      subjects. Changes in peak plasma viscosity ranged from -7% to 7% with similar
      changes for serum viscosity, from -8% to 10%, and a slightly greater range for
      plasma fibrinogen, -16% to 10%. In this cohort of normotriacylglycerolemic
      subjects, there were no significant postprandial changes in plasma viscosity or
      serum viscosity.

PMID- 8988911
TI  - Comparison of the effects of medium-chain triacylglycerols, palm oil, and high
      oleic acid sunflower oil on plasma triacylglycerol fatty acids and lipid and
      lipoprotein concentrations in humans.
AB  - Although medium-chain triacylglycerols (MCTs, composed of medium-chain fatty
      acids 8:0 and 10:0) have long been described as having neutral effects on serum
      cholesterol concentrations, experimental evidence supporting this claim is
      limited. In a randomized, crossover, metabolic-ward study, we compared the lipid
      effects of a natural food diet supplemented with either MCTs, palm oil, or high
      oleic acid sunflower oil in nine middle-aged men with mild hypercholesterolemia.
      Rather than having a neutral effect, MCT oil produced total cholesterol
      concentrations that were not significantly different from those produced by palm
      oil (MCT oil: 5.87 +/- 0.75 mmol/L; palm oil: 5.79 +/- 0.72 mmol/L) but
      significantly higher than that produced by high oleic acid sunflower oil (5.22 +/
      0.52 mmol/L). Low-density-lipoprotein (LDL)-cholesterol concentrations
      paralleled those of total cholesterol. MCT oil tended to result in higher
      triacylglycerol concentrations than either palm oil or high oleic acid sunflower
      oil, but this difference was not significant. There were no differences in high
      density-lipoprotein cholesterol concentrations. The palmitic acid and total
      saturated fatty acid content of plasma triacylglycerols in the MCT-oil diet was
      not significantly different from that in the palm oil diet. On the basis of
      percentage of energy, this study suggests that medium-chain fatty acids have one
      half the potency that palmitic acid has at raising total and LDL-cholesterol
      concentrations.

PMID- 8988913
TI  - Kinetic modeling of folate metabolism through use of chronic administration of
      deuterium-labeled folic acid in men.
AB  - This study was conducted as an initial investigation of in vivo folate kinetics
      in healthy men (n = 4) and made use of a chronic-administration protocol with
      stable-isotope labeling. Subjects were given 0.453 mumol (200 micrograms) total
      folic acid in aqueous solution daily throughout the 18-wk study while they
      consumed self-selected folate-adequate diets. After a 2-wk pretrial period with
      unlabeled folic acid, subjects were given 0.227 mumol (100 micrograms) pteroyl-L
      [2H4]glutamic acid/d ([2H4]folic acid) combined with 0.227 mumol nonlabeled folic
      acid or [2H2]pteroylhexaglutamic acid/d for the next 8 wk; then for the next 8 wk
      the [2H4]folic acid was withdrawn and the subjects received only nonlabeled folic
      acid. Little unmetabolized folic acid was excreted in urine. Isotopic enrichment
      of urinary folate during [2H4]folic acid administration and withdrawal was
      consistent with a kinetic model having a rapid turnover pool and a slow turnover
      pool. In contrast with previous two-pool models, provisions were made for folate
      turnover by urinary folate excretion (as measured here) and by fecal excretion
      and catabolic processes. The precision of modeling will be improved in future
      studies by measurement of enrichment of additional pools. However, this study
      shows clearly the slow turnover of the whole-body folate pool (< or = 1% per day)
      and the feasibility of further long-term kinetic analysis.

PMID- 8988912
TI  - Folate deficiency in rats induces DNA strand breaks and hypomethylation within
      the p53 tumor suppressor gene.
AB  - Folate is essential for the de novo biosynthesis of purines and thymidylate, and
      is an important mediator in the transfer of methyl groups for DNA methylation.
      Folate deficiency, therefore, could contribute to abnormal DNA integrity and
      methylation patterns. We investigated the effect of isolated folate deficiency in
      rats on DNA methylation and DNA strand breaks both at the genomic level and
      within specific sequences of the p53 tumor suppressor gene. Our data indicate
      that folate deficiency induces DNA strand breaks and hypomethylation within the
      p53 gene. Such alterations either did not occur or were chronologically delayed
      when examined on a genome-wide basis, indicating some selectivity for the exons
      examined within the p53 gene. Folate insufficiency has been implicated in the
      development of several human and experimental cancers, and aberrations within
      these regions of the p53 gene that were examined in this study are thought to
      play an integral role in carcinogenesis. The aforementioned molecular alterations
      may therefore be a means by which dietary folate deficiency enhances
      carcinogenesis.

PMID- 8988914
TI  - Pupillary threshold as an index of population vitamin A status among children in
      India.
AB  - Two hundred seven vitamin A-deficient southern Indian children aged 1-7 y (mean
      age: 56.9 mo) underwent testing of dark-adapted visual and pupillary thresholds
      in their village setting according to a previously reported protocol. One hundred
      thirty (62.8%) of the children also underwent serum retinol testing, and 178
      (86.0%) participated in a randomized, placebo-controlled vitamin A dosing trial
      with pre- and postdose testing of dark-adaptation threshold. Most subjects (184
      of 207, 88.9%) were able to complete pupillary testing, an objective sign
      requiring minimal cooperation, including a high proportion of the youngest
      children (72.2% of subjects aged 2 y). The proportion of children completing
      visual threshold testing, which requires greater understanding and cooperation,
      was significantly smaller than that able to complete pupillary testing (131 of
      207, 63.3%; P < 0.0001, chi square). At baseline (predosing), the mean serum
      retinol concentration declined in linear fashion with a higher pupillary
      threshold (0.73 mumol/L with a score < or = 4; 0.47 mumol/L with a score > or =
      8; P < 0.01). The mean pupillary threshold for these highly vitamin A-deficient
      Indian children (-0.622 log cd/m2) was significantly higher than that for 136
      more moderately deficient Indonesian children (-0.985 log cd/m2; P < 0.001, two
      sample t test) and 56 normal American children (-1.335 log cd/m2; P < 0.0001, two
      sample t test). The improvement in pupillary dark-adaptation testing was not
      significant for children receiving vitamin A or placebo, though there was a
      nonsignificant trend toward greater improvement in children receiving vitamin A
      (P = 0.2, two-sample t test). Pupillary threshold testing represents a new,
      noninvasive, practical, and seemingly valid approach to assessing the vitamin A
      status of a moderately to severely deficient preschool population.

PMID- 8988915
TI  - Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy
      elderly men and women.
AB  - Wintertime declines in vitamin D lead to increased concentrations of parathyroid
      hormone (PTH) and accelerated bone loss in postmenopausal women. We conducted
      this study to compare calcidiol (25-hydroxyvitamin D) concentrations of men and
      women, to examine the influence of season, travel, vitamin D intake, and other
      variables on these concentrations, and to compare associations between calcidiol
      and PTH concentrations in elderly men and women. In this cross-sectional study of
      182 men and 209 women aged > 65 y, mean calcidiol concentrations were higher in
      men than in women overall (mean +/- SD: 82.4 +/- 35.8 compared with 68.9 +/- 32.1
      nmol/L, P < 0.001). In the subset measured in winter (February-May), plasma
      calcidiol concentrations were lower and not significantly different in men (59.4
      +/- 21.8, n = 52) and women (57.7 +/- 23.4 nmol/L, n = 83). In a multiple
      regression model, calcidiol concentrations were positively influenced by
      wintertime travel (P = 0.012), vitamin D intake (P = 0.002), and time spent
      outdoors (P = 0.096) and negatively influenced by weight (P < 0.001) and age (P =
      0.039). Plasma calcidiol and serum PTH concentrations were inversely related,
      with PTH rising slowly as calcidiol concentrations declined below 110 nmol/L (95
      CI: 60, 168 nmol/L). More than 90% of the men and women had calcidiol
      concentrations below this value in the wintertime. The high prevalence of lower
      wintertime calcidiol values may increase risk of bone loss in elderly men and
      women.

PMID- 8988916
TI  - Copper status of young men consuming a low-copper diet.
AB  - A study was conducted in 11 young men to evaluate the effect of a low-copper diet
      on indexes of copper status and to define an amount of dietary copper at which
      adequate copper status could not be maintained. The young men were confined to a
      metabolic research unit for 90 d. The study was divided into three periods, with
      dietary copper as the only variable. Dietary copper was 0.66 mg/d for 24 d, 0.38
      mg/d for 42 d, and 2.49 mg/d for 24 d. Plasma copper, ceruloplasmin activity,
      ceruloplasmin concentration, and erythrocyte superoxide dismutase (SOD) were
      measured at selected time points during each dietary copper period. Urine was
      collected throughout the study. Plasma copper, ceruloplasmin concentration and
      activity, and urinary copper declined significantly during the lowest dietary
      copper period. Plasma copper, ceruloplasmin concentration, and urinary copper
      increased in response to repletion. The average erythrocyte SOD concentration was
      lower during the depletion period than in the periods before or after depletion,
      but it did not decline significantly over time in the depletion period. The
      results suggest that these indexes are sensitive to copper depletion; that 0.38
      mg Cu/d is not sufficient to maintain copper status in normal, healthy young men;
      and that the minimum dietary copper requirement is between 0.4 and 0.8 mg/d.

PMID- 8988918
TI  - Analysis of body water compartments in relation to tissue depletion in clinically
      stable patients with chronic obstructive pulmonary disease.
AB  - Tissue depletion often occurs in patients with chronic obstructive pulmonary
      disease (COPD), even in those that are weight-stable. Limited data are available,
      however, about changes in body water compartments in chronic wasting diseases
      such as COPD. The purpose of this study was to measure body composition in severe
      COPD patients with special attention to fat-free mass (FFM) depletion and the
      distribution of body water compartments. Total body water (TBW) and extracellular
      water (ECW) were measured by deuterium and sodium bromide dilution techniques,
      respectively, in 38 COPD patients (age: 65 +/- 9 y, forced expiratory volume in 1
      s: 38 +/- 14% of predicted) in a stable clinical condition. FFM was calculated by
      assuming a hydration coefficient of 73%. Underweight patients [body mass index
      (BMI; in kg/m2) < or = 21] were characterized by a significantly lower percentage
      fat mass than normal-weight patients, but no significant difference was found in
      the ratio of ECW to intracellular water (ICW)(BMI < or = 21: 0.72 +/- 0.12, BMI >
      21: 0.71 +/- 0.16; NS). When the study population was divided into depleted
      patients (FFM/height2 < or = 15 kg/m2) and nondepleted patients (FFM/height2 > 15
      kg/m2), there was no significant difference in the percentage fat mass, but the
      ECW-ICW ratio was significantly higher in the depleted patients (0.78 +/- 0.16)
      than in the nondepleted patients (0.66 +/- 0.12, P < 0.05); this was most
      pronounced in women. In conclusion, it was found that COPD patients with extreme
      FFM wasting are characterized by an increased ECW-ICW ratio despite a relatively
      spared fat mass.

PMID- 8988917
TI  - Dietary fat and insulin sensitivity in a triethnic population: the role of
      obesity. The Insulin Resistance Atherosclerosis Study (IRAS)
AB  - From the Insulin Resistance Atherosclerosis Study (IRAS), 1173 men and women of
      African-American, non-Hispanic white, and Hispanic ethnicity with no history of
      diabetes were included in an evaluation of the cross-sectional relation of
      habitual dietary fat intake with insulin sensitivity (SI) as assessed by minimal
      model analysis of a 12-sample, insulin-modified frequently sampled intravenous
      glucose-tolerance test. Dietary intake was measured by a food-frequency interview
      modified to enhance sensitivity to food choices within the three ethnic groups.
      Percentage of energy from total fat was associated with rank of SI (SI(rank); r =
      -0.06, P = 0.03), with log fasting insulin (r = 0.10, P < 0.001), and with BMI (r
      = 0.10, P < 0.001). Multiple-linear-regression models included SI(rank) as the
      dependent variable, dietary fat (g/d) as the primary independent variable
      adjusted sequentially for total energy, other covariates, body mass index, and
      waist-hip circumference ratio (WHR). For all subjects combined, total fat intake
      was inversely related to SI(rank), but this association was not significant (P =
      0.14) and was attenuated by adjustment for body mass index and WHR (P = 0.44).
      The association of total fat (g/d) with SI(rank) differed significantly (P <
      0.01) for obese compared with nonobese individuals. Higher fat intake was
      associated with lower SI(rank) among obese (beta = -1.40, P = 0.03) but not among
      nonobese persons (beta = 0.16, P = 0.80). Among the obese (body mass index < or =
      63), adjustment for body mass index largely accounted for the observed
      association of dietary fat with SI(rank). These findings were generally
      consistent for monounsaturated, polyunsaturated, and saturated fats. Among
      individuals already at increased risk for non-insulin-dependent diabetes mellitus
      because of obesity, high intake of dietary fat may worsen insulin sensitivity.
      This effect may be mediated by the relation of dietary fat to obesity.

PMID- 8988919
TI  - Nutritional status of children with acute lymphoblastic leukemia: a longitudinal
      study.
AB  - To evaluate the nutritional consequences of acute lymphoblastic leukemia and its
      treatment, 15 children with leukemia were studied. Anthropometric data, fat-free
      mass by impedance, energy intake, and resting energy expenditure (REE) were
      determined at diagnosis and on days 22, 36, and 71 of the treatment. Interleukin
      (IL)-1 beta, IL-6, interferon-gamma, and tumor necrosis factor were also
      measured. Fifteen healthy control subjects were matched for age and sex. Body
      weight and height and body composition were comparable at all times of the study,
      although three children were underweight at diagnosis (weight-for-height < 85% of
      French standards). Although two different methods were used for dietary recall in
      the two groups, energy intake expressed as a percentage of normal recommended
      values for age and sex was lower in patients than in control subjects (104 +/-
      19%) on day 1 (47 +/- 32.1%) and day 22 (58 +/- 24%), but was comparable on day
      36 (85 +/- 71%) and day 71 (85 +/- 48%). This low energy intake involved both
      carbohydrates and fats. Energy and carbohydrate intakes improved significantly
      during the study in patients. The nonprotein respiratory quotient (RQ) in
      patients was significantly lower than in control subjects (0.84 +/- 0.04) on day
      1 (0.79 +/- 0.02) but was comparable on day 71. The REE of the patients on day 1
      (5057.8 +/- 1588.4 kJ/24 h) and day 71 (4844.7 +/- 116.1 kJ/24 h) and of the
      control subjects (4313.8 +/- 823.5 kJ/24 h) was not significantly different.
      Cytokines remained undetectable on days 1, 36, and 71. The results showed that at
      the time of diagnosis and during this period of chemotherapy there was no
      evidence of raised REE. The poor intakes during the first month of chemotherapy
      were recent as shown by the parents' questionnaire responses and the absence of
      consequences in body composition. The transient decrease in RQ seemed to be an
      adaptative mechanism to the poor carbohydrate intake. No indication of
      undernutrition in the patients as a group was evident during the first 71 d of
      treatment although further long-term nutritional assessment is needed.

PMID- 8988920
TI  - Vitamin E and carotenoids in gastric biopsies: the relation to plasma
      concentrations in patients with and without Helicobacter pylori gastritis.
AB  - The carotenoids--lycopene and alpha- and beta-carotene-- and alpha-tocopherol
      were measured in plasma and in mucosal biopsies in normal subjects and in those
      infected with Helicobacter pylori. Two indexes of the presence of the reactive
      oxygen species malondialdehyde and chemiluminescence were measured in biopsies
      taken from adjacent sites in the same patient. In general, plasma and mucosal
      concentrations of all antioxidants correlated well and were of a similar order or
      magnitude in plasma and mucosa. There was no significant difference between the
      slope of the regression lines nor an overall difference in the concentrations of
      these antioxidants between the H. pylori-positive and control groups, indicating
      an absence of effect of H. pylori infection. However, a marked difference was
      seen in chemiluminescence and malondialdehyde concentrations in biopsies. For
      chemiluminescence this was highly significant. These findings confirm the
      presence of free radicals in the mucosa of H. pylori-infected patients and
      suggest therefore that the lipid-soluble antioxidants have either no role in
      protecting mucosal cells from free radical damage or, if they are able to
      scavenge these species, they are then rapidly regenerated to their original forms
      by redox and other processes.

PMID- 8988921
TI  - Wheat bread supplemented with depolymerized guar gum reduces the plasma
      cholesterol concentration in hypercholesterolemic human subjects.
AB  - Recent human studies have shown that the physiologic effects of guar gum are not
      diminished by partial depolymerization of its galactomannan fraction. We
      evaluated the effect of depolymerized guar galactomannan on fasting plasma
      cholesterol and triacylglycerol concentrations in healthy volunteers with
      moderately raised plasma cholesterol concentrations (range: 5.2-8.0 mmol/L). This
      study was designed as a randomized, double-blind crossover of two 3-wk feeding
      periods separated by a 4-wk washout period. Control and guar wheat breads were
      prepared by a commercial bread-making process. Subjects (n = 11) were asked to
      replace their normal bread with that provided, receiving control bread for one 3
      wk period and guar bread for the other period, without altering their baseline
      diet. Subjects recorded their intake of foods for 6 consecutive days on three
      occasions during the study. Fasting venous blood samples (10 mL) were taken from
      subjects on two consecutive mornings at the start and end of each feeding period.
      No significant changes in body weight or dietary intake were recorded in the
      control and guar bread periods. There was a significant reduction (10%) in total
      plasma cholesterol concentration after the guar treatment (P < 0.001), mainly
      because of a reduction in the low-density-lipoprotein-cholesterol fraction. No
      changes in plasma high-density-lipoprotein-cholesterol or triacylglycerol
      concentrations were seen. The cholesterol-lowering effect of partially
      depolymerized guar gum appears to be of a magnitude similar to that of high
      molecular-weight guar gum used in earlier studies.

PMID- 8988922
TI  - Postprandial cholecystokinin release and gastric emptying in patients with
      bulimia nervosa.
AB  - This study was designed to investigate the biological underpinnings of the
      observed deficit in satiety in patients with bulimia nervosa. Eight women with
      bulimia nervosa and 10 age- and weight-matched control subjects consumed three
      laboratory meals consisting of 200, 400, and 600 g of a radiolabeled liquid meal.
      For 1 h after each meal, blood samples were obtained at 10-min intervals for
      measurement of cholecystokinin concentration and gastric emptying was measured.
      Subjects also completed perceptual rating scales at 10-min intervals. Compared
      with control subjects, patients with bulimia nervosa showed a blunting of
      postprandial cholecystokinin release, particularly with larger meal sizes, as
      well as delayed gastric emptying. Increasing meal size was associated with
      increased desire to binge eat in patients but not in control subjects. These data
      lend support to a model in which increased gastric capacity, perhaps resulting
      from repeated binge eating, gives rise to delayed gastric emptying and blunted
      postprandial cholecystokinin release, leading to an impaired satiety response,
      which tends to perpetuate the illness.

PMID- 8988923
TI  - Combined effects of lipid peroxidation and antioxidant status on carotid
      atherosclerosis in a population aged 59-71 y: The EVA Study. Etude sur le
      Vieillisement Arteriel.
AB  - There are few epidemiologic studies of the effects of lipid peroxidation and
      antioxidant status on atherosclerosis. The relation of lipid peroxidation
      evaluated by thiobarbituric acid-reactive substances (TBARS) and biological
      markers of antioxidant status to ultrasonographically assessed carotid
      atherosclerosis was examined from baseline data of a longitudinal study on
      cognitive and vascular aging (Etude sur le Vieillisement Arteriel, the EVA
      Study). The study sample was composed of 1187 mean and women aged 59-71 y without
      any history of coronary artery disease or stroke. Ultrasound examination included
      measurements of intima-media thickness (IMT) on the common carotid arteries
      (CCAs) and at the site of plaques. After adjustment for conventional
      cardiovascular risk factors, erythrocyte vitamin E was significantly and
      negatively associated with CCA-IMT in both men and women whereas plasma selenium
      and carotenoids were not. No association was found between TBARS and CCA-IMT in
      either sex. However, TBARS were significantly higher in men with carotid plaques
      than in those without. This association was strengthened in men with
      concentrations of erythrocyte vitamin E, plasma selenium, and carotenoids below
      the lowest quartile. Our findings give some epidemiologic support to the
      hypothesis that lipid peroxidation and low antioxidant status are involved in the
      early phases of atherosclerosis.

PMID- 8988924
TI  - Plasma glucose turnover and oxidation during hemodialysis: nutritional effect of
      dialysis fluid.
AB  - Mass transfer of glucose from dialysis fluid into patients is a source of energy
      and a form of nutrition during hemodialysis. The effect of glucose mass transfer
      on endogenous glucose metabolism and the overall nutritional importance of
      glucose transfer is not known. Rates of plasma glucose turnover and oxidation
      were determined by radioisotope-dilution techniques in patients with chronic
      renal failure (CRF) in the basal state, during hemodialysis, and during the
      infusion of glucose at a rate similar to the mass transfer rate (Mt: 6.6 +/- 0.7
      mumol.min-1.kg-1). Rates of plasma glucose turnover (11.8 +/- 0.8 mumol.min-1.kg
      1) and oxidation (4.0 +/- 0.4 mumol.min-1.kg-1) and contribution of glucose
      oxidation to the metabolic rate were similar to those of control subjects both in
      the basal state and during glucose infusion. During hemodialysis with acetate and
      glucose, the plasma glucose turnover rate was similar to that in the basal state,
      but the energy from glucose oxidation was less (P < or = 0.02) even though energy
      expenditure was increased by 21%. Immediate oxidation of plasma glucose and
      acetate accounted for 65% of the patients' energy expenditure. Energy (1172 kJ)
      from acetate Mt and glucose Mt surpassed the patients' energy requirements,
      offsetting the utilization of endogenous fuels, a sparing effect equivalent to 31
      g fat or 70 g carbohydrate. Rates of plasma glucose turnover and oxidation during
      bicarbonate-glucose and glucose-free acetate hemodialysis were similar to that
      during acetate-glucose hemodialysis. However, without glucose or acetate in the
      bath fluid, a deficit as much as 669 kJ must be met by the oxidation of
      endogenous fuels. Addition of organic nutrients that supply energy to dialysis
      fluids may over time be a beneficial supplemental treatment for the malnutrition
      and body wasting commonly observed in CRF.

PMID- 8988925
TI  - Coffee consumption and plasma total homocysteine: The Hordaland Homocysteine
      Study.
AB  - The health consequences of coffee drinking remain controversial. We report on an
      association between coffee consumption and the concentration of total
      homocysteine (tHcy) in plasma, a risk factor for cardiovascular disease and for
      adverse pregnancy outcome. The study population consisted of 7589 men and 8585
      women 40-67 y of age and with no history of hypertension, diabetes, ischemic
      heart disease, or cerebrovascular disease. They were recruited from Hordaland
      county of western Norway in 1992-1993. Daily use of coffee was reported by 89.1%
      of the participants, of whom 94.9% used caffeinated filtered coffee. There was a
      marked positive dose-response relation between coffee consumption and plasma
      tHcy, which was stronger than the relation between coffee and total serum
      cholesterol. In 40-42-y-old men, mean tHcy was 10.1 mumol/L for nonusers and 12.0
      mumol/L for drinkers of > or = 9 cups of coffee/d. Corresponding tHcy
      concentrations in 40-42-y-old women were 8.2 and 10.5 mumol/L, respectively.
      Although coffee drinking was associated with smoking and lower intake of vitamin
      supplements and fruit and vegetables, the coffee-tHcy association was only
      moderately reduced after these variables were adjusted for. The combination of
      cigarette smoking and high coffee intake was associated with particularly high
      tHcy concentrations. A strong inverse relation between tea and tHcy concentration
      in univariate analysis was substantially attenuated after smoking and coffee
      drinking were adjusted for. The results of the present report should promote
      future studies on tHcy as a possible mediator of adverse clinical effects related
      to heavy coffee consumption.

PMID- 8988926
TI  - Effect of early vitamin A supplementation on cell-mediated immunity in infants
      younger than 6 mo.
AB  - One hundred twenty infants were randomly assigned to receive either 15 mg vitamin
      A or placebo with each of three DPT/OPV (diphtheria, pertussis, tetanus/oral
      polio vaccine) immunizations at monthly intervals. Sixty-two received vitamin A
      and 58 received placebo. One month after the third supplementation dose, the
      response to the delayed cutaneous hypersensitivity test [multitest cell-mediated
      immunity (CMI) skin evaluation] for tetanus, diphtheria, and tuberculin (purified
      protein derivative, PPD) was the same in the vitamin A and placebo infants. The
      number of anergic infants was 17 (27%) and 19 (33%) in the vitamin A and placebo
      groups, respectively. The number of positive tests among well-nourished infants
      was significantly higher than that in malnourished infants irrespective of
      supplementation (P < 0.001). Among the infants with adequate serum retinol
      concentrations (> 0.7 mumol/L) after supplementation, the vitamin A-supplemented
      infants had a significantly higher proportion of positive CMI tests than the
      placebo infants (chi-square test: 8.99, P = 0.008). Among the infants with low
      serum retinol concentrations (< 0.7 mumol/L) after supplementation, vitamin A
      supplementation had no effect on CMI response. These results indicate that CMI in
      young infants was positively affected by vitamin A supplementation only in those
      infants whose vitamin A status was adequate (ie, serum retinol > 0.7 mumol/L) at
      the time of the CMI test. CMI was consistently better in well-nourished infants
      irrespective of supplementation.

PMID- 8988927
TI  - Cryptosporidium infection in infancy as a cause of malnutrition: a community
      study from Guinea-Bissau, west Africa.
AB  - Cryptosporidium parvum causes persistent diarrhea in young children in developing
      countries. To determine the interaction between nutritional status and
      cryptosporidiosis, an open cohort of 1064 children younger than 3 y of age was
      followed for 1441 child-years by weekly diarrhea recall visits. A total of 5072
      weight and 4264 height measurements was made. There were no tendencies of low
      weight (P = 0.38) or height (P = 0.16) in children who acquired
      cryptosporidiosis. Cryptosporidiosis in infancy was accompanied by an estimated
      weight loss of 392 g (95% CI: 247, 538 g) in boys and 294 g (95% CI: 109, 479 g)
      in girls, corresponding to 3.7% and 2.9% of mean weight, respectively, at 2 y of
      age. No significant catch-up growth covered for this loss in weight. A similar
      effect in linear growth was shown (P = 0.02). Although it has been suggested that
      the effect of infections on nutrition is usually transient because of catch-up
      growth, the present study suggests that cryptosporidiosis in infancy has a
      permanent effect on growth.

PMID- 8988929
TI  - Zinc deficiency in young children.

PMID- 8988928
TI  - Epidemiology of iron deficiency anemia in Zanzibari schoolchildren: the
      importance of hookworms.
AB  - Anemia is estimated to affect one-half of school-age children in developing
      countries. The school years are an opportune time to intervene, and interventions
      must be based on sound epidemiologic understanding of the problem in this age
      group. We report on the distribution of iron deficiency and anemia across age,
      sex, anthropometric indexes, and parasitic infections in a representative sample
      of 3595 schoolchildren from Pemba Island, Zanzibar. Iron status was assessed by
      hemoglobin, erythrocyte protoporphyrin (EP), and serum ferritin concentrations
      from a venous blood sample. Overall, 62.3% of children were anemic (hemoglobin <
      110 g/L), and 82.7% of anemia was associated with iron deficiency. The overall
      prevalence of iron-deficient erythropoiesis (EP > 90 mumol/mol heme) was 48.5%,
      and the prevalence of exhausted iron stores (serum ferritin < 12 micrograms/L)
      was 41.3%. In bivariate analyses, iron status was slightly better in girls than
      in boys, and was better in children aged 7-11 y than in those older or younger.
      Hemoglobin but not EP or serum ferritin concentrations were lower in stunted
      children. Infection with malaria, Trichuris trichiura, Ascaris lumbricoides, and
      hookworms were all associated with worse iron status; the association with
      hookworms was strongest by far. In multivariate analyses, hookworm infection
      intensity was the strongest explanatory variable for hemoglobin, EP, and serum
      ferritin. Sex, malarial parasitemia, A. lumbricoides infection, and stunting were
      also retained in the multivariate model for hemoglobin. Twenty-five percent of
      all anemia, 35% of iron deficiency anemia, and 73% of severe anemia were
      attributable to hookworm infection; < 10% of anemia was attributable to A.
      lumbricoides, malaria infection, or stunting. We conclude that anthelminthic
      therapy is an essential component of anemia control in schoolchildren in whom
      hookworms are endemic, and should be complemented with school-based iron
      supplementation.

PMID- 8988930
TI  - Better understanding of folate nutrition through chemistry.

PMID- 8988931
TI  - Insulin resistance in atherosclerosis.

PMID- 8988932
TI  - Role of isoflavones in the cholesterol reduction by soy proteins in the clinic.

PMID- 8988933
TI  - Retrograded (RS3) but not uncooked (RS2) resistant starch lowers fecal ammonia
      concentrations in healthy men.

PMID- 8988934
TI  - Validation of dietary assessment methods.

PMID- 8988935
TI  - Effects of dietary palmitic and oleic acids on lipoprotein cholesterol.

PMID- 8988936
TI  - Introduction and summary of the dietary and nutritional methods and findings in
      the Multiple Risk Factor Intervention Trial.

PMID- 8988937
TI  - Brief description of the Multiple Risk Factor Intervention Trial.
AB  - The Multiple Risk Factor Intervention Trial (MRFIT) was one of the coronary heart
      disease prevention trials recommended to the National Heart and Lung Institute in
      1971 as an alternative to a national single-factor dietary trial, which was
      judged to be infeasible. MRFIT was a randomized, primary prevention trial,
      conducted at 22 US clinical centers from 1973 to 1982 to test whether lowering
      elevated serum cholesterol and diastolic blood pressure and ceasing cigarette
      smoking would reduce coronary heart disease mortality. Men 35-57 y of age (n =
      12,866) with one or more of these risk factors were randomly assigned to the
      special intervention (SI) or usual care (UC) group and followed for 6-8 y. UC men
      were given information on risk factors, referred to their usual sources of care,
      and reexamined annually. SI participants received group and individual counseling
      on a fat-modified diet, a stepped-care drug treatment program for diastolic
      hypertension (after an initial attempt at blood pressure control by weight
      reduction, if indicated), and, for cigarette smokers, counseling aimed at
      cessation. SI men had risk factor assessments every 4 mo and annual examinations
      that were generally identical to those given to UC men and that always included
      measurement of blood cholesterol concentration. A listing of variables measured
      at each visit along with the design and major mortality results of MRFIT are
      included in this chapter.

PMID- 8988938
TI  - Methods of dietary and nutritional assessment and intervention and other methods
      in the Multiple Risk Factor Intervention Trial.
AB  - Various dietary assessment instruments were used in the Multiple Risk Factor
      Intervention Trial (MRFIT), either to assist with the special intervention
      program or to assess trial outcomes. For the latter purpose, the 24-h recall was
      the main method and was selected with the understanding that the single recall
      collected at baseline and at most annual visits--considered by itself--would be
      useful mainly for assessing groups rather than individuals. Major components of
      the data collection and analysis system developed for the 24-h recall included
      central training and certification of nutritionists, a central nutrient coding
      system, and a food grouping system to assist interventionists in using recall
      data for counseling. Several additional nutritional assessment methods were used
      for men in the special intervention group only to assist them in attaining the
      dietary goals. These goals consisted chiefly of reduced intake of saturated fat
      and cholesterol and a modest increase in intake of polyunsaturated fat; total fat
      intake was also decreased, primarily for control of energy intake. Short-term
      success at attainment of these nutritional goals was evaluated by means of 3-d
      food records collected before the intervention and after the initial 10-wk
      intensive intervention period. The MRFIT nutrient goals, which became more
      vigorous at certain points in the trial, were translated into food patterns.
      Adherence to these food patterns was also assessed by scoring of 3-d records and
      by subjective evaluation by nutritionists throughout the trial. Methods of
      collecting other trial data are also described in this chapter.

PMID- 8988939
TI  - Method issues in dietary data analyses in the Multiple Risk Factor Intervention
      Trial.
AB  - The selection process in the Multiple Risk Factor Intervention Trial caused
      relations between risk factors to differ between participants who were randomly
      assigned into the study and the screening population. Cigarette smoking, blood
      pressure, and serum cholesterol were moderately inversely related to each other
      in the randomly assigned population whereas these relations in the unselected
      population were direct and small in magnitude. This problem was addressed by
      covariate adjustment in analyses. The selection process also created an
      artificially high initial mean concentration of serum cholesterol; the mean
      plasma concentration at the second screening was 15 mg/dL lower than at the first
      screening. Most of this difference is attributable to regression to the mean. To
      account for this problem, emphasis was placed on change in plasma cholesterol
      over time, calculated from the second-screening measurement. Examination of the
      reliability of nutrition data based on one 24-h dietary recall showed that
      nutrient-biochemical relations are subject to considerable regression-dilution
      bias. The ratios of "within" to "between" components of variability were
      typically between one and four. Analyses in which multiple follow-up measures
      were averaged are emphasized in this monograph. Men assigned to the special
      intervention group reported considerable reductions in total energy intake, which
      was not consistent with observed weight loss. The most likely explanation for
      this is underreporting or underconsumption the day before the recall. To
      partially adjust for this, nutrient data are often expressed both in absolute
      units and as nutrient densities.

PMID- 8988940
TI  - Food group and nutrient intakes at baseline in the Multiple Risk Factor
      Intervention Trial.
AB  - This chapter relates food and nutrient intakes at baseline to other facets of
      reported dietary behavior, major risk factors, and sociodemographic
      characteristics of men in the Multiple Risk Factor Intervention Trial. Intakes of
      total fat (38.4% of energy), saturated fatty acids (14.2%), and dietary
      cholesterol (492 mg/d) were similar to amounts seen in the first and second
      National Health and Nutrition Examination Surveys in the 1970s and were generally
      lower than findings from studies in the 1960s. There were inverse relations
      between total serum cholesterol and intakes of total fat, saturated and
      monounsaturated fatty acids, and dietary cholesterol. These paradoxical
      associations were largely attributable to findings in the 21% of men who reported
      following a special diet, indicating that use of such a diet increases with
      severity of hypercholesterolemia. Fat intake was directly related to number of
      meals per week eaten away from home, and to cigarette smoking. Patterns of food
      and nutrient intake were similar for men stratified by baseline blood pressure
      and antihypertensive treatment. Intake of total energy and percentages from
      various dietary fats decreased with age, as did use of sucrose and caffeine.
      White men consumed more dairy products than did other ethnic groups, whereas
      black men consumed more eggs, sugars, and sweets. Asians had the highest intake
      of cereal foods. Those with more education ate less high-fat meat products, more
      fruit, and more polyunsaturated oils, but also more high-fat dairy products and
      less breads and cereals; they also drank more alcohol.

PMID- 8988942
TI  - Relation of changes in dietary lipids and weight, trial years 1-6, to changes in
      blood lipids in the special intervention and usual care groups in the Multiple
      Risk Factor Intervention Trial.
AB  - For men in the special intervention (SI) group of the Multiple Risk Factor
      Intervention Trial, the average decrease in serum total cholesterol was 16.9
      mg/dL (6.7%); for men in the usual care (UC) group, the average decrease was 9.7
      mg/dL (3.8%). The difference between the two groups for plasma total cholesterol
      was 6.2 mg/dL. Plasma low-density-lipoprotein (LDL) cholesterol decreased 10.6
      mg/dL (6.6%) in SI men and 5.4 mg/dL (3.4%) in UC men. Mean weight losses were
      3.0 lb (1.36 kg) and 0.1 lb (0.05 kg) for SI and UC men, respectively. Change in
      blood total cholesterol was directly related to baseline concentration; for men
      with serum total cholesterol > or = 220 mg/dL, those in the SI group decreased
      their total cholesterol by 7.8% (design goal: 10%) and those in the UC group by
      4.8% (expected: 0%). Change in dietary lipid intake (summarized by the Keys
      score) for SI men was significantly related to changes in blood total
      cholesterol, LDL cholesterol, and triglyceride, but not to change in high-density
      lipoprotein (HDL) cholesterol. Controlled for weight change, coefficients for
      Keys score change were smaller but remained significantly related to each blood
      lipid except HDL cholesterol. Weight loss was associated with favorable effects
      on all blood lipids. Influences of change in diet and weight on blood lipids were
      quantitatively less for hypertensive men for serum total cholesterol, HDL
      cholesterol, and triglyceride than for nonhypertensive men. Nonsmokers had
      greater decreases than smokers in blood total cholesterol, LDL cholesterol, and
      triglyceride.

PMID- 8988941
TI  - Food group and macronutrient intakes, trial years 1-6, in the special
      intervention and usual care groups in the Multiple Risk Factor Intervention
      Trial.
AB  - This chapter presents changes in dietary intake reported by men in the special
      intervention (SI) and usual care (UC) groups from baseline through 6 y of follow
      up in the Multiple Risk Factor Intervention Trial. Changes in nutrients by SI men
      after 1 y of following the intensive intervention program were as follows:
      reduced intake of total fat (from 38.4% to 34.3% of energy), saturated fatty
      acids (14.2% to 10.4% of energy), and cholesterol (448 to 263 mg/d), and
      increased intake of polyunsaturated fatty acids (from 6.4% to 8.6% of energy).
      These changes were maintained and did not increase through the remaining 5 y. UC
      men reported small changes in similar directions. Most of the change in saturated
      fatty acid intake by SI participants was from high-fat meat and high- and medium
      fat dairy products. Reduction in dietary cholesterol was achieved primarily by
      substantial decreases in intake of eggs and high-fat meats. Several baseline
      factors were associated with amount of dietary change in SI men. Greater changes
      were seen in men with higher baseline serum cholesterol concentrations, in those
      not consuming a special diet, in nonsmokers followed by lighter smokers, in
      hypertensive than in non-hypertensive men, in older participants, in white than
      in black men, in moderate drinkers than in nondrinkers or those consuming > or =
      22 drinks/wk, and in those with no "stressful life events" than in those
      reporting one or more life events.

PMID- 8988943
TI  - Adherence to dietary recommendations in the special intervention group in the
      Multiple Risk Factor Intervention Trial.
AB  - This chapter presents findings on adherence to the Multiple Risk Factor
      Intervention Trial eating pattern by special intervention participants, on the
      basis of measures other than the 24-h dietary recall and blood cholesterol
      concentrations. These additional assessments included subjective ratings by a
      nutritionist, used during follow-up years 1 and 2, and a food record rating that
      was calculated from a 3-d food record, used during years 3-6. An additional tool
      used during the latter part of the trial was a checklist for evaluating degree of
      shortfall of the participant's diet from recommendations, level of motivation
      toward adherence, and factors in the social environment potentially influencing
      dietary behavior. Subjective ratings and food record ratings indicated that
      approximately 40-65% of participants were good or excellent adherers, with
      declines in these percentages over time. There were consistent strong relations
      between these ratings and change in serum cholesterol. Checklist evaluations gave
      similar overall findings, with about one-half to three-quarters of participants
      rated positively on infrequency of deviation from the eating pattern, motivation,
      and conducive environment. Several baseline traits predicted adherence. Adherence
      was better in older participants, in white than in black men, in nondrinkers, in
      those with fewer stressful life events, in those eating away from home less
      often, in less overweight men (although heavier participants exhibited greater
      changes in serum cholesterol, perhaps reflecting their poorer baseline diets), in
      those with higher serum cholesterol and diastolic blood pressure, and in
      nonsmokers.

PMID- 8988944
TI  - Nutritional adequacy of diets reported at baseline and during trial years 1-6 by
      the special intervention and usual care groups in the Multiple Risk Factor
      Intervention Trial.
AB  - This chapter addresses whether a fat-modified diet as implemented by special
      intervention participants in the Multiple Risk Factor Intervention Trial affected
      intake of vitamins and minerals, and whether nutritional adequacy was altered by
      this dietary intervention. Despite likely underreporting of intake, for men in
      the special intervention group, most mean intakes of 15 micronutrients estimated
      from 24-h recalls were above established recommended dietary allowances. A few
      means were slightly below; lowest was zinc at 77% (from 98% at baseline) followed
      by calcium at 79% (from 102% at baseline). Calculated as nutrient densities (per
      1000 kcal), nutrients that were below indexes of nutritional quality (the
      corresponding standard based on nutrient density) during follow-up, although not
      reduced below baseline by this measure, were vitamin D, calcium, iron
      (marginally), and zinc. Analyses by food groups indicated that intake of these
      nutrients might have been improved by greater replacement of high- and medium-fat
      dairy products with low-fat dairy products (for vitamin D and calcium) and of
      high-fat meats with low-fat meats, fish, or poultry (for iron and zinc), or
      (because iron was adequate) by increasing consumption of vegetables and whole
      grain products. The safety of the eating pattern was further confirmed by more
      favorable micronutrient profiles in men who adhered best to the intervention
      program, as measured by degree of serum cholesterol reduction and weight loss.

PMID- 8988946
TI  - Relation of dietary fiber to blood lipids in the special intervention and usual
      care groups in the Multiple Risk Factor Intervention Trial.
AB  - This chapter addresses relations between intake of fiber--total, soluble, and
      insoluble--and blood lipids in the Multiple Risk Factor Intervention Trial
      through use of baseline data (single measurement), averages of four to five 24-h
      recalls and blood lipid determinations collected during annual follow-up
      examinations, and change from baseline to follow-up. No significant associations
      were observed at baseline. Consistent highly significant inverse associations
      were seen in analyses of follow-up measurements. Results from change data were of
      intermediate strength and consistency. These variations were in all likelihood
      due to the low reliability of a single 24-h recall at baseline for determination
      of dietary intake and change in intake for individuals. From follow-up data,
      plasma total and low-density-lipoprotein (LDL) cholesterol concentrations were
      lower by approximately 5 mg/dL for men in the special intervention group in
      quintile 5 of total fiber intake (25 g/d) compared with men in quintile 1 (8
      g/d), after adjustment for average body mass index and intake of alcohol,
      saturated and polyunsaturated fatty acids, and dietary cholesterol. Results were
      similar for men in the usual care group. There were no adverse effects on high
      density-lipoprotein cholesterol, nor any consistent associations with plasma
      triglycerides. Thus, increasing dietary fiber can provide additional reduction in
      blood total and LDL cholesterol and consequent improvement in the lipid profile,
      over and above the beneficial effects of a fat-modified diet.

PMID- 8988945
TI  - Relation of dietary carbohydrates to blood lipids in the special intervention and
      usual care groups in the Multiple Risk Factor Intervention Trial.
AB  - This chapter explores relations between reported intake of dietary carbohydrates
      and measurements of plasma lipids at baseline and during trial years 1-6 of the
      Multiple Risk Factor Intervention Trial. With control for dietary lipids,
      alcohol, and other factors, total carbohydrate intake at baseline was inversely
      related to baseline plasma total cholesterol and high-density-lipoprotein (HDL)
      cholesterol; starch and other simple carbohydrates were unrelated to plasma
      lipids and sucrose was inversely related to HDL cholesterol. During trial years 1
      6, men assigned to the special intervention group increased their intake of
      starch and other simple carbohydrates as they decreased their fat intake, and
      lowered their intakes of refined and processed sucrose. Total carbohydrate intake
      of these men was inversely related to total, low-density-lipoprotein (LDL), and
      HDL cholesterol. Starch and sucrose intakes were also inversely related to HDL
      cholesterol. In contrast, intake of other simple carbohydrates was directly
      related to HDL, and inversely related to plasma total and LDL cholesterol. For
      men in the highest quintile of intake of other simple carbohydrates compared with
      men in the lowest quintile, plasma total cholesterol was lower by 3.6 mg/dL, LDL
      cholesterol was lower by 4.3 mg/dL, and HDL cholesterol was higher by 1.6 mg/dL.
      Findings were generally similar for men in the usual care group.

PMID- 8988947
TI  - Relation of body mass and alcohol, nutrient, fiber, and caffeine intakes to blood
      pressure in the special intervention and usual care groups in the Multiple Risk
      Factor Intervention Trial.
AB  - This chapter presents analyses of relations of dietary variables to blood
      pressure, systolic (SBP) and diastolic (DBP), for men in the special intervention
      (SI) and usual care (UC) groups in the Multiple Risk Factor Intervention Trial.
      For each dietary factor, analyses were done at baseline, for trial years 1-6, and
      for change from baseline to years 1-6. Analyses were done for all participants
      and for men receiving or not receiving antihypertensive drug treatment and were
      controlled for age, race, education, serum cholesterol, smoking, special diet
      status, and (for specific nutrients) body mass index and alcohol intake. Nutrient
      data for trial years 1-6, which are based on four or five dietary recalls per
      man, are more reliable than the baseline or change data, which are based on only
      one recall. Therefore, this summary focuses on data for trial years 1-6, for SI
      and UC men pooled. Regression analyses confirmed direct independent relations of
      body mass index, alcohol intake, sodium, and ratio of sodium to potassium to SBP
      and DBP, and an inverse relation of potassium to SBP and DBP. Dietary starch was
      directly related to SBP and DBP; dietary saturated fatty acid and cholesterol and
      Keys score were directly related to DBP; dietary magnesium, fiber, and caffeine
      were inversely related to SBP and DBP; and dietary protein, polyunsaturated fatty
      acids, the ratio of polyunsaturated to saturated fatty acid, and other simple
      carbohydrates were inversely related to DBP. Method problems, all tending to
      produce underestimations, are also reviewed.

PMID- 8988948
TI  - Relation of food and nutrient intakes to body mass in the special intervention
      and usual care groups in the Multiple Risk Factor Intervention Trial.
AB  - This chapter summarizes weight and body mass index findings of the Multiple Risk
      Factor Intervention Trial and then focuses on relations of food group and
      nutrient intakes to weight change during follow-up. Results were qualitatively
      similar for the special intervention (SI) and usual care groups. Weight change
      was related both to dietary composition averaged over follow-up recalls and to
      changes from baseline. Greater weight loss compared with little change or gain
      was related to greater reductions from baseline and lower percentages of energy
      reported at follow-up from refined sucrose, total fat, and saturated and
      monounsaturated fatty acids. Greater weight loss was also associated with greater
      reductions in and lower intakes of cholesterol and energy. In both groups, these
      patterns reflected lower percentages of energy from medium-fat dairy products,
      eggs, highly saturated visible fats, crackers and snacks, refined sugars and
      sweets, and additionally for SI men, lower percentages of energy from high-fat
      meats, dairy products, and baked goods and desserts. In both groups weight loss
      was related to increased or higher percentages of energy from total and non
      sucrose simple carbohydrates, and to fiber intake, and for SI men, to higher
      percentages of energy from starch. These nutrient patterns involved higher
      percentages of energy from low-fat dairy products, breads and cereals, fruit, and
      vegetables, and for SI men, from low-fat baked goods and desserts. Overall,
      substantial weight loss was associated with a diet of lower energy density and
      with higher intakes of several essential micronutrients.

PMID- 8988949
TI  - Relation of smoking at baseline and during trial years 1-6 to food and nutrient
      intakes and weight in the special intervention and usual care groups in the
      Multiple Risk Factor Intervention Trial.
AB  - This chapter describes dietary composition according to cigarette smoking status
      at baseline and changes in smoking status during follow-up for men in the special
      intervention (SI) and usual care (UC) groups of the Multiple Risk Factor
      Intervention Trial. Five patterns of smoking behavior were defined: 1) sustained
      nonsmoking, 2) early (years 1-2 of the trial) sustained quitting, 3) late (years
      3-6 of the trial) sustained quitting, 4) recidivism, and 5) continued smoking. SI
      men who quit smoking showed greater favorable changes in dietary lipid
      composition and micronutrient intake than did continued smokers, and these
      changes were in many instances as great as favorable changes made by nonsmokers.
      On the other hand, SI men who quit smoking gained an average of 3.8 lb (1.7 kg),
      in contrast with nonsmokers who lost an average of 6.4 lb (2.9 kg). The gain by
      SI quitters was, however, less than that by UC quitters, who gained 6.5 lb (3.0
      kg). Moreover, despite weight gain, net change in high-density-lipoprotein (HDL)
      cholesterol for SI quitters was positive. With the associated decrease in low
      density-lipoprotein (LDL) cholesterol, early SI quitters had the most improvement
      in ratio of LDL to HDL among all subgroups. Thus, unfavorable nutritional
      patterns of smokers put them at double jeopardy regarding cardiovascular and
      other chronic diseases; additionally, long-term risks can be improved not only by
      smoking cessation but also by achievement of healthier eating patterns.

PMID- 8988951
TI  - Molecular biology, III. Tracking DNA: the Southern blot.

PMID- 8988952
TI  - Psychomotor symptoms of depression.
AB  - OBJECTIVE: The authors summarize current knowledge regarding the psychomotor
      symptoms of depression. METHOD: Findings from the objective quantification of
      psychomotor symptoms are reviewed, and methodological issues are considered. The
      contemporary empirical literature regarding the diagnostic, prognostic, and
      potential pathophysiologic significance of psychomotor symptoms is summarized.
      RESULTS: It has been repeatedly shown that depressed patients differ from normal
      and psychiatric comparison groups with regard to objectively quantified gross
      motor activity, body movements, speech, and motor reaction time. Course of
      illness, diurnal variation, medication status, sex, and age are associated with
      agitation and retardation and should be controlled when one is studying
      psychomotor symptoms. Psychomotor symptoms in depression may have unique
      significance. They have high discriminative validity, may be the only symptoms of
      depression that distinguish depression subtypes, and are predictive of good
      response to tricyclic antidepressants. Results of brain imaging and biochemical
      studies link depression and motor symptoms to abnormalities in the basal ganglia
      and basal ganglia/thalamo-cortical circuits. CONCLUSIONS: The investigation of
      psychomotor disturbance in depression is specifically consistent with neo
      Kraepelinian standards for the study of psychiatric disorders. Our current
      knowledge of psychomotor symptoms is conceptually obscure, yet a large body of
      evidence specifies their manifestation and supports their significance.
      Identifying the incidence of abnormal motor behaviors in depressed patients and
      assessing the component processes that accompany and determine their
      manifestation may be important advances in the study of psychomotor symptoms in
      depression.

PMID- 8988953
TI  - Premorbid brain size as a determinant of reserve capacity against intellectual
      decline in Alzheimer's disease.
AB  - OBJECTIVE: Both the magnitude of brain atrophy and premorbid brain size determine
      the volume of the brain affected by Alzheimer's disease. To examine the
      possibility that premorbid brain volume is a determinant of cognitive reserve in
      patients with Alzheimer's disease, the relation between diffuse brain atrophy and
      cognitive decline and the impact of premorbid brain size on cognitive decline
      were studied in patients with Alzheimer's disease. METHOD: By measuring whole
      brain volume and intracranial volume in 60 patients with probable Alzheimer's
      disease, mild to moderate in severity, with the use of high-resolution magnetic
      resonance imaging and image processing, the authors studied the impact of
      premorbid brain volume and magnitude of diffuse brain atrophy on cognitive
      functions. On the basis of the normative brain-calvarium relationship derived
      from data an 28 healthy adults and the total intracranial volume measure of each
      patient, the magnitude of brain atrophy and premorbid brain volume were
      estimated. RESULTS: After control for the effects of age, sex, and education as
      confounding factors, it was found that the Alzheimer's disease patients'
      intelligence was correlated both positively with premorbid brain volume and
      negatively with magnitude of brain atrophy, while impairments in language and
      memory were correlated with magnitude of brain atrophy but not with premorbid
      brain volume. CONCLUSIONS: These findings partially support the hypothesis that
      premorbid brain volume is a determinant of reserves against intellectual decline
      in Alzheimer's disease.

PMID- 8988954
TI  - Effects of Alzheimer's disease severity on cerebrospinal fluid norepinephrine
      concentration.
AB  - OBJECTIVE: Although loss of noradrenergic neurons in the locus ceruleus has been
      consistently demonstrated postmortem in Alzheimer's disease, several small
      studies suggest that indices of central noradrenergic activity increase with the
      severity of Alzheimer's disease in living patients. The authors estimated the
      effect of Alzheimer's disease severity on central noradrenergic activity by
      comparing the CSF norepinephrine concentrations of subjects with Alzheimer's
      disease in earlier and advanced stages. The effect of normal aging on CSF
      norepinephrine also was determined. METHOD: Lumbar punctures were performed in 49
      subjects with Alzheimer's disease of mild or moderate severity, 25 subjects with
      advanced Alzheimer's disease, 42 normal older subjects, and 54 normal young
      subjects. Advanced Alzheimer's disease was defined prospectively by a Mini-Mental
      State score of less than 12. Norepinephrine was measured by radioenzymatic assay.
      RESULTS: CSF norepinephrine concentration was significantly higher in the
      patients with advanced Alzheimer's disease (mean = 279 pg/ml, SD = 122) than in
      those with mild to moderate severity (mean = 198 pg/ml, SD = 89), normal older
      subjects (mean = 219 pg/ml, SD = 88), or normal young subjects (mean = 154 pg/ml,
      SD = 53). CSF and plasma norepinephrine levels and mean arterial blood pressure
      all were higher in the older subjects than in the young subjects. CONCLUSIONS:
      Despite the loss of locus ceruleus neurons in Alzheimer's disease, the aging
      associated high concentration of CSF norepinephrine is retained in the earlier
      stages of Alzheimer's disease and increases further as the disease progresses.
      Increased brain noradrenergic activity may contribute to the agitated behaviors
      or cognitive deficits of patients with advanced Alzheimer's disease.

PMID- 8988955
TI  - Prophylactic efficacy of phenelzine and imipramine in chronic atypical
      depression: likelihood of recurrence on discontinuation after 6 months'
      remission.
AB  - OBJECTIVE: Demonstration of antidepressant efficacy beyond 6 months has
      infrequently been addressed, and no long-term efficacy data exist for patients
      with chronic atypical depression. METHOD: Sixty patients with atypical depression
      (according to Columbia University criteria) of at least 2 years' duration and who
      had improved with imipramine or phenelzine were stabilized for 6 months and then
      randomly continued the same medication or placebo for 6 months. RESULTS: Several
      baseline differences suggested that patients who entered the discontinuation
      trial on a regimen of phenelzine were more chronically depressed than the
      imipramine-treated patients. Survival analysis showed a marked advantage for
      phenelzine relative to placebo. In addition, patients switched to placebo from
      phenelzine experienced a recurrence of depressive symptoms significantly more
      often than patients switched to placebo from imipramine. Patients maintained with
      imipramine did not have lower relapse rates than those switched from imipramine
      to placebo. Recurrence rates were 23% for patients maintained on a regimen of
      phenelzine, 41% for those maintained on a regimen of imipramine, 47% for those
      switched from imipramine to placebo, and 87% for placebo-treated patients
      originally treated with phenelzine. CONCLUSIONS: Patients with chronic atypical
      depression are at high risk of recurrence if phenelzine is withdrawn 6 months
      after initial improvement. Similar findings were not demonstrated for imipramine;
      this replicates acute trials demonstrating imipramine's relative ineffectiveness
      in patients with atypical depression. Differences in recurrence rates after the
      switch to placebo from phenelzine and imipramine could be due to the two drugs'
      different mechanisms of action or to baseline differences in the two populations.

PMID- 8988956
TI  - Effect of pindolol in hastening response to fluoxetine in the treatment of major
      depression: a double-blind, placebo-controlled trial.
AB  - OBJECTIVE: In two preliminary studies, pindolol produced robust results in
      hastening clinical response to antidepressant drugs in depressed patients.
      Validity of those pilot studies was limited by use of an open-label, unblinded
      study design, and so the authors conducted a double-blind, placebo-controlled
      trial to assess the effectiveness of pindolol in hastening response to
      fluoxetine. METHOD: Drug-free outpatients with major depression were concurrently
      treated with fluoxetine (20 mg/day) and either placebo or pindolol (5.0 mg b.i.d.
      or 2.5 mg t.i.d.), for 6 weeks, in a randomized, double-blind manner. After 6
      weeks, all patients received fluoxetine and placebo and were followed for 3
      further weeks in a single-blind manner. RESULTS: Forty-three patients completed
      at least 1 week of the protocol. Rates of partial remission after 2 weeks of
      treatment with fluoxetine and either pindolol or placebo were 17% (four of 23
      patients) and 20% (four of 20 patients), respectively. At study completion, 65%
      of the patients (N = 28) demonstrated at least a partial remission, and there was
      no difference between treatment groups. The pindolol group, but not the placebo
      group, demonstrated significant reductions in blood pressure and pulse rate. The
      average time to remission and the rates of attrition, overall response, and side
      effects were similar in the two groups. CONCLUSIONS: These findings do not
      support the efficacy of pindolol in hastening clinical response in patients
      treated with fluoxetine.

PMID- 8988957
TI  - Phenomenology of adolescent and adult mania in hospitalized patients with bipolar
      disorder.
AB  - OBJECTIVE: Although available data suggest that bipolar disorder most commonly
      begins in adolescence, it has often been underrecognized and misdiagnosed in this
      age group. The authors hypothesized that this might in part be because adolescent
      mania is phenomenologically different from adult mania. To test this hypothesis,
      they compared a cohort of adolescents hospitalized for acute mania with a group
      of hospitalized acutely manic adults. METHOD: The authors compared symptomatic
      differences between 40 adolescent (ages 12-18 years) and 88 adult (ages 19-45
      years) bipolar patients hospitalized for acute mania. They also compared the two
      groups with respect to demographic characteristics, psychiatric comorbidity,
      family history, and short-term outcome. RESULTS: Compared with adults, adolescent
      patients displayed a significantly higher rate of mixed bipolar disorder and a
      significantly lower rate of psychotic features (by DSM-III-R criteria), as well
      as higher ratings for many depressive symptoms (including suicidality and
      depressed mood) and lower ratings for thought disorder and delusions. Adolescents
      also displayed a significantly lower rate of substance abuse and significantly
      higher rates of familial mood disorder and drug abuse or dependence. CONCLUSIONS:
      Significant differences were found in the phenomenology of adolescent and adult
      mania in this study. The reasons for these differences are not known. Possible
      explanations include artifact due to methodological limitations and differences
      between adolescents and adults in familial loading for mood or substance use
      disorders or in developmental or maturational stage.

PMID- 8988959
TI  - Correlation between reduced in vivo benzodiazepine receptor binding and severity
      of psychotic symptoms in schizophrenia.
AB  - OBJECTIVE: Although there is evidence from postmortem studies suggestive of
      deficient inhibitory neurotransmission of gamma-aminobutyric acid (GABA) in
      schizophrenia, no direct in vivo evidence has been obtained to date. The authors
      used single photon emission computed tomography (SPECT) with iodine-123-labeled
      iomazenil ([123I]iomazenil), a radioligand that selectively binds with high
      affinity to the benzodiazepine subunit of the GABAA receptor complex in the human
      brain, to investigate the presence of benzodiazepine receptor abnormalities in
      the cerebral cortex of living subjects with schizophrenia. METHOD: Dynamic
      [123I]iomazenil SPECT was performed in 15 patients (14 patients with DSM-III-R
      schizophrenia and one with schizophreniform disorder) and 12 healthy subjects
      over a period of 2 hours. The time-integral method was used to generate ratios of
      "specific" to "nonspecific" [123I]iomazenil binding at equilibrium for several
      cortical regions. RESULTS: No overall between-group differences in benzodiazepine
      receptor binding were found, but significant correlations emerged between the
      severity of schizophrenic symptoms and [123I]iomazenil binding in limbic cortical
      regions: positive symptom scores were negatively correlated with benzodiazepine
      receptor binding in the left medial temporal region, and negative symptoms were
      inversely related to receptor binding in the medial frontal region. These
      correlations were not significant when a Bonferroni correction for multiple
      comparisons was applied. CONCLUSIONS: These preliminary results are consistent
      with previous research implicating limbic cortical regions in the pathophysiology
      of schizophrenia, suggesting that reduced inhibitory GABAergic tone in these
      areas may contribute to the appearance of schizophrenic symptoms.

PMID- 8988958
TI  - Effects of methylphenidate on regional brain glucose metabolism in humans:
      relationship to dopamine D2 receptors.
AB  - OBJECTIVE: The authors' goals were to determine whether baseline dopamine
      activity contributes to response to methylphenidate and to assess the pattern of
      metabolic responses associated with enhanced dopamine activity. METHOD: They used
      positron emission tomography with 2-deoxy-2[18F]fluoro-D-glucose to evaluate the
      effects of two sequential doses of methylphenidate on brain metabolism in 15
      healthy subjects. Dopamine D2 receptor availability was measured with
      [11C]raclopride to evaluate its relation to methylphenidate-induced metabolic
      changes. RESULTS: Methylphenidate increased brain metabolism in six subjects,
      decreased it in two, and did not change it in seven; however, it consistently
      increased cerebellar metabolism. Methylphenidate significantly increased
      "relative" (region relative to the whole brain) metabolism in the cerebellum and
      decreased it in the basal ganglia. Regional metabolic changes in the cerebellum
      and the frontal and temporal cortices were significantly correlated with D2
      availability. Frontal and temporal metabolism were increased in subjects with
      high D2 receptors and decreased in subjects with low D2 receptors. CONCLUSIONS:
      Methylphenidate induced variable changes in brain metabolism, but it consistently
      increased cerebellar metabolism. It also induced a significant reduction in
      relative metabolism in the basal ganglia. The significant association between
      metabolic changes in the frontal and temporal cortices and in the cerebellum and
      D2 receptors suggests that methylphenidate's metabolic effects in these brain
      regions are due in part to dopamine changes and that differences in D2 receptors
      may be one of the mechanisms accounting for the variability in response to
      methylphenidate.

PMID- 8988960
TI  - Childhood-onset schizophrenia: biological markers in relation to clinical
      characteristics.
AB  - OBJECTIVE: The purpose of this study was to examine the relationships between
      clinical and neurobiological measures of childhood-onset schizophrenia. It was
      hypothesized that there would be a more striking pattern in the rare cases with
      very early onset than is seen in subjects with later onset. METHOD: Premorbid,
      clinical, prenatal, perinatal, and magnetic resonance imaging brain measures were
      examined in 29 children and adolescents who met the DSM-III-R criteria for
      schizophrenia with onset before age 12. Specifically, gender, premorbid
      adjustment, and clinical symptoms were examined in relation to cerebral volume,
      ventricular volume, and maternal obstetrical complications. RESULTS: Males were
      more likely to have had an insidious onset than females. There was a significant
      negative correlation between score on the Scale for the Assessment of Negative
      Symptoms and total cerebral volume. CONCLUSIONS: These neurobiological
      associations support the continuity of early-onset schizophrenia with the later
      onset disorder; the striking association between smaller cerebral volume and
      negative symptoms suggests a more homogeneous or more potent neurobiological
      basis for very early-onset schizophrenia.

PMID- 8988961
TI  - Cerebrospinal fluid monoamine metabolites in childhood-onset schizophrenia.
AB  - OBJECTIVE: Pediatric studies of cerebrospinal fluid (CSF) monoamine metabolites
      in childhood-onset schizophrenia may help to elucidate both pathophysiology and
      treatment response in early-onset psychosis. METHOD: CSF homovanillic acid (HVA),
      5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)
      and serum prolactin were measured during drug-free and antipsychotic medication
      conditions in 18 patients (mean age = 14.2 years, SD = 1.7) who had onset of
      schizophrenia by age 12 (mean age at onset = 9.9 years, SD = 1.8). Relationships
      between changes in CSF monoamines and serum prolactin and clinical outcome were
      examined, and the degree of change in CSF monoamines in response to clozapine
      treatment was compared with that for 16 patients with later-onset schizophrenia.
      RESULTS: Despite patients' significant clinical improvement with treatment, CSF
      monoamine concentrations and ratios of HVA/5-HIAA and HVA/MHPG did not
      significantly change with 6 weeks of either haloperidol or clozapine treatment.
      Serum prolactin levels increased during haloperidol treatment. Clozapine had
      similar effects on CSF monoamines in patients with childhood- and later-onset
      schizophrenia. CONCLUSIONS: While these data are compatible with continuity
      between childhood- and later-onset schizophrenia, they also highlight the
      complexity of the biochemical events mediating clinical changes in schizophrenia.

PMID- 8988962
TI  - Superiority of carbohydrate-deficient transferrin to gamma-glutamyltransferase in
      detecting relapse in alcoholism.
AB  - OBJECTIVE: The usefulness of carbohydrate-deficient transferrin is widely
      accepted in screening (male) population samples for heavy alcohol consumption,
      but its role in relapse detection is not convincingly established. The authors
      therefore compared the diagnostic value of carbohydrate-deficient transferrin
      with the commonly used gamma-glutamyltransferase in identifying relapsed
      alcoholics during outpatient aftercare. METHOD: The patients were 101 male
      alcoholics who entered a 6-month rehabilitation program after hospital
      detoxification. Drinking status was assessed by means of self- and collateral
      reports obtained during regular contacts with the rehabilitation team; relapse
      was defined as consumption of any alcohol. Visits occurred weekly during month 1,
      biweekly during month 2, and every 4 weeks during months 3-6. At every visit a
      blood sample was taken for measurement of carbohydrate-deficient transferrin and
      gamma-glutamyltransferase. RESULTS: The proportion of men who reported relapse
      was 25.6% per scheduled contact on average. Positive predictive values indicated
      that relapse was identified with a 76.2% probability by carbohydrate-deficient
      transferrin values above the upper normal limit, in contrast to a 32.9% chance
      with gamma-glutamyltransferase. Carbohydrate-deficient transferrin was especially
      useful in detecting early relapses during the initial rehabilitation phase, when
      gamma-glutamyltransferase values had not normalized. Because of the longer half
      life of gamma-glutamyltransferase, it had some value with a 4-week monitoring
      schedule in detecting new drinking episodes in alcoholics whose previous results
      had been normal. CONCLUSIONS: Carbohydrate-deficient transferrin proved to be
      superior to gamma-glutamyltransferase in relapse detection in an outpatient care
      setting for alcoholics.

PMID- 8988963
TI  - Behavioral and neuroendocrine responses to m-chlorophenylpiperazine in subtypes
      of alcoholics and in healthy comparison subjects.
AB  - OBJECTIVE: The purpose of this study was to explore central serotonergic
      functions in subgroups of alcoholics and in healthy comparison subjects. METHOD:
      The mixed serotonin (5-HT) agonist/antagonist m-chlorophenylpiperazine (m-CPP)
      was administered to male alcoholic patients who were classified according to the
      criteria of von Knorring et al. as type I alcoholics (late onset) (N = 16) or
      type II alcoholics (early onset with antisocial traits) (N = 24) and to 22
      healthy comparison subjects. Psychological, physiological, and neuroendocrine
      measures were obtained before and after the m-CPP infusion. RESULTS: m-CPP
      elicited subtype-related differential effects among the alcoholics; the type I
      alcoholics reported more anger and anxiety, and the type II alcoholics reported
      increased euphoria and a greater likelihood of drinking. The healthy comparison
      subjects exhibited a greater increase in plasma ACTH response to the m-CPP
      infusion than the alcoholics regardless of subtype. CONCLUSIONS: Differences in
      certain 5-HT receptor functions may explain some of the clinical characteristics
      that differentiate the type II and type I subgroups of alcoholic patients.
      Furthermore, alcoholics may have reduced sensitivity of 5-HT2C receptors in
      comparison with healthy subjects.

PMID- 8988964
TI  - Violence by patients admitted to a private psychiatric hospital.
AB  - OBJECTIVE: The authors determined the rates and patterns of violence toward
      persons by psychiatric patients before admission to the inpatient service of the
      Payne Whitney Clinic and determined which factors were associated with a greater
      risk of violence. METHOD: During hospitalization, 763 patients were interviewed
      by a research assistant using a structured interview instrument. The interviewer
      inquired about demographic and socioeconomic information and about history of
      violence and alcohol and drug use. RESULTS: Having physically attacked another
      person in the month before admission was equally likely among male (13.6%) and
      female (14.7%) patients. The patterns of violence were similar for men and women
      in terms of target, severity of injuries, use of a weapon, and place of
      occurrence. Univariate analyses showed that only youth was associated with
      violence for male patients, while youth, low socioeconomic status, substance
      abuse, and axis II pathology were associated with a greater risk of violence for
      female patients. Logistic regression analyses showed that recent cocaine use was
      significantly associated with violence by female patients when age, socioeconomic
      status, and axis II pathology were controlled for. For male patients, recent
      heroin use was related to a greater risk of violence. CONCLUSIONS: The frequency
      of violence by female patients was 150% higher than it was in a study at the
      Payne Whitney Clinic a decade ago. The frequency of violence by male patients was
      50% higher than it was a decade ago. In the current study, substance abuse was
      associated with greater risk of violence by patients.

PMID- 8988965
TI  - Reform said or done? The case of Emilia-Romagna within the Italian psychiatric
      context.
AB  - OBJECTIVE: The authors sought to evaluate how the services required by the
      Italian Psychiatric Reform of 1978 were implemented in Emilia-Romagna, a region
      of 4 million inhabitants in Northern Italy. METHOD: All psychiatric facilities
      were monitored from 1978 to 1994 to determine the number and rates of admissions,
      average duration of stay, average intake, and percent of beds occupied at
      inpatient facilities as well as the number of patients residing in former mental
      hospitals and the number and rates of first contacts with mental health community
      centers. RESULTS: Three mental hospitals out of nine were closed during the
      period, and the number of patients who resided in mental hospitals declined from
      4,798 to 655. By 1994, there were 145 community centers, 48 day treatment
      centers, 12 general hospital psychiatric wards, three university psychiatric
      clinics, seven private psychiatric clinics, 24 psychiatric residences, and 123
      supervised apartments that were operating as alternatives to asylums. The overall
      rate of inpatient admissions remained stable, but compulsory admissions gradually
      decreased by 35% throughout the period. First contacts at outpatient centers
      increased by 17.9% from 1984 to 1991. CONCLUSIONS: The shift from a hospital
      based to a community-based psychiatric system of care, as foreseen by the Italian
      psychiatric reform, seems feasible. Some general political, administrative, and
      social backup conditions appear crucial to ensure the good outcome of this
      process.

PMID- 8988966
TI  - Characterizing quality of life among patients with chronic mental illness: a
      critical examination of the self-report methodology.
AB  - OBJECTIVE: The purposes of the study were 1) to characterize the quality of life
      of three patient groups with chronic mental illness, 2) to evaluate differences
      in reported life quality among the three groups, and 3) to evaluate the validity
      of a self-report methodology by comparing these results with several objective
      indicators of life quality. METHOD: The study group consisted of chronically
      mentally ill patients with schizophrenia (N = 69), bipolar disorder (N = 37), or
      major depression (N = 35). Subjects were administered the Quality of Life Index,
      and comparisons of both objective and self-report life quality indices were made
      among the three groups. Quality of life ratings of these subjects were also
      compared with those of patients with a chronic physical illness. RESULTS: The two
      groups with mood disorders reported significantly lower scores on the Quality of
      Life Index than the patients with schizophrenia. Moreover, the scores on the
      Quality of Life Index for patients with schizophrenia were very similar to those
      of the comparison group of physically ill patients. The opposite trend emerged
      when groups were compared with respect to objective indicators of life quality.
      Schizophrenic patients experienced more objectively aversive life circumstances
      than either of the affectively disturbed groups. CONCLUSIONS: The validity of
      self-report measures of life satisfaction is questioned, particularly for use
      with affectively disturbed populations, since scores may be influenced by
      affective bias, poor insight, and recent life events.

PMID- 8988967
TI  - Refusal of medical treatment: psychiatric emergency?

PMID- 8988968
TI  - McLean Hospital.

PMID- 8988969
TI  - Identification of children with pediatric autoimmune neuropsychiatric disorders
      associated with streptococcal infections by a marker associated with rheumatic
      fever.
AB  - OBJECTIVE: The authors' goal was to determine whether a trait marker of rheumatic
      fever susceptibility (labeled D8/17) could identify children with pediatric
      autoimmune neuropsychiatric disorders (obsessive-compulsive disorder and tic
      disorders) associated with streptococcal infections (PANDAS). METHOD: Blood
      samples obtained from 27 children with PANDAS, nine children with Sydenham's
      chorea, and 24 healthy children were evaluated for D8/17 reactivity. Individuals
      were defined as D8/17 positive if they had 12% or more D8/17+ cells. RESULTS: The
      frequency of D8/17-positive individuals was significantly higher in both patient
      groups than it was among the healthy volunteers: 85% of the children with PANDAS
      and 89% of the children with Sydenham's chorea, compared with 17% of the healthy
      children, were D8/17 positive. Further, the mean number of D8/17+ cells was
      similar in the two patient groups and was significantly higher in these groups
      than in the group of healthy children. CONCLUSIONS: These results suggest that
      there may be a subgroup of D8/17-positive children who present with clinical
      symptoms of obsessive-compulsive disorder and Tourette's syndrome, rather than
      Sydenham's chorea, but who have similar poststreptococcal autoimmunity.

PMID- 8988970
TI  - Association analysis of the catechol O-methyltransferase gene and bipolar
      affective disorder.
AB  - OBJECTIVE: Catechol O-methyltransferase (COMT) is an enzyme that inactivates
      catecholamines. Two common COMT alleles determine high and low activity of the
      enzyme. Previous studies using biochemical methods found lower enzyme activity in
      patients with major depression and bipolar disorder in comparison with control
      values, suggesting that a dysfunction in catecholamine metabolism may be related
      to the etiology of depression. METHOD: The authors studied two recently described
      DNA polymorphisms at the COMT gene (a silent C256G mutation and a structural
      mutation, Val-108-Met) in 88 patients with bipolar disorder and in 113 healthy
      comparison subjects, all of Spanish origin. RESULTS: The frequency of the C256
      allele was 0.58 in the patients and 0.54 in the comparison subjects. The
      frequency of the Val108 variant was 0.57 for both the patients and the comparison
      subjects. No allelic or genotypic associations were observed. CONCLUSIONS: The
      lack of association suggests that the COMT gene is not a major risk factor for
      bipolar disorder.

PMID- 8988971
TI  - Lower levels of nucleoside triphosphate in the basal ganglia of depressed
      subjects: a phosphorous-31 magnetic resonance spectroscopy study.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether the concentration of
      beta-nucleoside triphosphate is lower in the basal ganglia of depressed subjects.
      METHOD: In vivo 31P magnetic resonance spectra were acquired from a 45-cm3 region
      surrounding the basal ganglia of 35 unmedicated depressed subjects and 18
      comparison subjects. RESULTS: beta-Nucleoside triphosphate, which arises
      primarily from beta-ATP, was 16% lower in the depressed subjects than in the
      comparison subjects. CONCLUSIONS: The low level of beta-nucleoside triphosphate
      is consistent with an abnormality of high-energy phosphate metabolism in the
      basal ganglia of subjects with major depression.

PMID- 8988972
TI  - Gender differences in cerebellar metabolism: test-retest reproducibility.
AB  - OBJECTIVE: The purpose of this study was to evaluate gender differences in
      baseline measures of regional brain metabolism and to assess their
      reproducibility. METHOD: Fifteen male and 13 female healthy subjects, whose mean
      age was 44 years, were tested with positron emission tomography and
      [18F]fluorodeoxyglucose (FDG) under resting conditions; eight of the men and 11
      of the women underwent a second FDG scan under the same conditions 4-6 weeks
      later to assess the reproducibility of the previous results. RESULTS: There were
      no differences in whole brain metabolism between the women and the men. In the
      first evaluation the female subjects showed significantly higher metabolism in
      the temporal poles and cerebellum than the male subjects. During the second
      evaluation the female subjects had significantly higher metabolism only in the
      cerebellum. CONCLUSIONS: This study documents significant and reproducible gender
      differences in cerebellar metabolism; their functional significance merits
      further evaluation.

PMID- 8988973
TI  - Lower risk of suicide during pregnancy.
AB  - OBJECTIVE: The authors determined the risk of suicide during pregnancy. METHOD:
      The autopsy reports of all female residents of New York City, 10-44 years old,
      who committed suicide from 1990 to 1993 were assessed for pregnancy. These data
      were compared with age-adjusted and race-adjusted standardized mortality ratios
      for women, which were calculated by using population data from the 1990 U.S.
      Census as well as data obtained from the New York City Health Department on the
      number of live births, spontaneous abortions, and induced abortions. RESULTS: The
      standardized mortality ratio for suicide during pregnancy was 0.33; that is, the
      number of suicides of pregnant women was only one-third of that expected.
      CONCLUSIONS: Despite the mood swings and stresses associated with pregnancy and
      impending childbirth, pregnant women have a significantly lower risk of suicide
      than women of childbearing age who are not pregnant.

PMID- 8988974
TI  - Can pulmonary complications cause schizophrenia remission?

PMID- 8988975
TI  - Virtual reality therapy for fear of flying.

PMID- 8988976
TI  - Pancreatitis associated with risperidone treatment?

PMID- 8988977
TI  - Social phobia and stuttering.

PMID- 8988978
TI  - Perfectionism in anorexia nervosa.

PMID- 8988979
TI  - Substance abuse and ADHD.

PMID- 8988980
TI  - Psychosis and etiology.

PMID- 8988981
TI  - On the new clinical case conferences.

PMID- 8988982
TI  - Taking care of money matters.

PMID- 8988983
TI  - Taking care of money matters.

PMID- 8988984
TI  - Homosexuality and older brothers.

PMID- 8988985
TI  - Homosexuality and older brothers.

PMID- 8988986
TI  - Homosexuality and older brothers.

PMID- 8988987
TI  - Dissociation in patients with borderline personality disorder.

PMID- 8988988
TI  - Physical health and negative life events.

PMID- 8988989
TI  - Origin of homovanillic acid in plasma.

PMID- 8988990
TI  - Outcome assessment and pulmonary artery catheterization: why does the debate
      continue?

PMID- 8988991
TI  - Cerebral ischemic disorders and cerebral oxygen balance during cardiopulmonary
      bypass surgery: preoperative evaluation using magnetic resonance imaging and
      angiography.
AB  - We compared the preoperative prevalence of small cerebral infarctions and carotid
      stenosis to jugular venous oxygen saturation (Sjvo2) during coronary artery
      bypass grafting (CABG). Sjvo2 served as an indicator of whether cerebral oxygen
      supply meets demand in patients on cardiopulmonary bypass (CPB). The study
      population consisted of 121 patients who were either older than 65 yr or had a
      history of cerebrovascular disease. The patients underwent preoperative cerebral
      magnetic resonance imaging (MRI) and cervical magnetic resonance angiography
      (MRA) to detect small cerebral infarctions and carotid artery stenosis. Patients
      with atherosclerosis of the ascending aorta were identified by intraoperative
      epiaortic ultrasonography. Liberation of emboli from the aorta in these patients
      was prevented by modification of the standard operation. From preoperative MRI
      and MRA, 65 patients (54%) had small cerebral infarctions in the white matter or
      basal ganglia and nine patients (7%) demonstrated moderate or severe stenosis in
      the carotid arteries. Thirteen patients (11%) had moderate or severe atheromatous
      disease of the ascending aorta. The severity of aortic atherosclerosis was
      significantly correlated with the grade of carotid stenosis (P < 0.05). In
      patients with small infarctions, Sjvo2 was significantly lower than in patients
      without infarctions (controls) at initiation of CPB, 30 min after aortic cross
      clamping, and during the rewarming period of CPB (P < 0.05). Thus, small cerebral
      infarctions were not uncommon in elderly patients undergoing CABG. Patients with
      small cerebral infarctions may be at risk for an imbalance in cerebral oxygen
      supply and demand during the rewarming period because they are unable to deliver
      the necessary compensatory blood flow.

PMID- 8988993
TI  - Clinical application of transorotracheal tube tracheal insufflation of oxygen in
      patients undergoing simple video-assisted thoracoscopic surgery.
AB  - Video-assisted thoracoscopic surgery (VATS) has been performed during
      ganglionectomy and bullectomy and usually requires a collapsed or immobilized
      lung. Transtracheal insufflation of oxygen (TRIO) maintains an immobilized lung,
      adequate oxygenation, and partial CO2 elimination but has never been used for
      VATS. We have simplified the TRIO design with a catheter inserted through the
      lumen of the orotracheal tube in what we call "transorotracheal tube TRIO" (TRIO
      TOTT) and investigated its clinical use on simple VATS. Eleven patients
      undergoing bullectomy for primary simple pneumothorax (PSP) were studied. During
      the performance of VATS, a 12-gauge suction catheter was inserted as our
      modification and connected to the gas outlet of an anesthetic machine. The flow
      rate of oxygen was maintained at 10 L/min. Blood gas was collected prior to TRIO
      TOTT, during TRIO-TOTT at 5, 10, 15, and 20 min, and 5 min after TRIO-TOTT. The
      blood gas data showed excellent oxygenation while the PaCO2 increased at a rate
      of 1.2 mm Hg/min compared to 3-4 mm Hg/min for apnea oxygenation. After 20 min,
      the mean +/- SEM PaO2 and PaCO2 were 428 +/- 27 and 65.0 +/- 2.6 mm Hg,
      respectively. We conclude that TRIO-TOTT is a simple, safe, and effective
      ventilation method for simple VATS.

PMID- 8988992
TI  - Hemodynamic effects, myocardial ischemia, and timing of tracheal extubation with
      propofol-based anesthesia for cardiac surgery.
AB  - Recent interest in earlier tracheal extubation after coronary artery bypass graft
      (CABG) surgery has focused attention on the potential benefits of a propofol
      based technique. We randomized 124 patients (34 with poor ventricular function)
      undergoing CABG surgery to receive either a propofol-based (5 mg.kg-1.h-1 prior
      to sternotomy, 3 mg.kg-1. h-1 thereafter; n = 58) or enflurane-based (0.2%-1.0%,
      n = 66) anesthetic. Induction of anesthesia consisted of fentanyl 15
      micrograms/kg and midazolam 0.05 mg/kg intravenously in both groups. The
      enflurane group received an additional bolus of fentanyl 5 micrograms/kg prior to
      sternotomy and fentanyl 10 micrograms/kg with midazolam 0.1 mg/kg at commencement
      of cardiopulmonary bypass (CPB). Patients receiving propofol were extubated
      earlier (median 9.1 h versus 12.3 h, P = 0.006), although there was no difference
      in time to intensive care unit (ICU) discharge (both 22 h, P = 0.54). Both groups
      had similar hemodynamic changes throughout (all P > 0.10), as well as metaraminol
      (P = 0.49) and inotrope requirements (P > 0.10), intraoperative myocardial
      ischemia (P = 0.12) and perioperative myocardial infarction (P = 0.50). The
      results of this trial suggest that a propofol-based anesthetic, when compared to
      an enflurane-based anesthetic requiring additional dosing of fentanyl and
      midazolam for CPB, can lead to a significant reduction in time to extubation
      after CABG surgery, without adverse hemodynamic effects, increased risk of
      myocardial ischemia or infarction.

PMID- 8988994
TI  - Preoperative acute hypervolemic hemodilution with hydroxyethylstarch: an
      alternative to acute normovolemic hemodilution?
AB  - Acute normovolemic hemodilution (ANH) may help to reduce demand for homologous
      blood but requires extra time and apparatus. A more simple procedure is acute
      hypervolemic hemodilution (HHD), where hydroxyethylstarch is administered
      preoperatively without removal of blood. In a prospectively randomized study we
      compared ANH (preoperatively 15 mL/kg autologous blood removal and replacement
      with 15 mL/kg of hydroxyethylstarch with HHD (15 mL/kg of hydroxyethylstarch
      administered preoperatively) in 49 patients undergoing hip arthroplasty. To avoid
      excessive intravascular volume, we used the vasodilating effect of isoflurane. No
      significant differences were found between groups (ANH, n = 23; HHD, n = 26) for
      intraoperative blood loss (ANH versus HHD, median [minimum-maximum]); 545 [295
      785] mL versus 520 [315-825] mL) and postoperative blood loss (730 [525-945] mL
      versus 780 [495-895] mL), postoperative hemoglobin, hemotocrit, platelet count or
      coagulation variables, and transfusion requirements (ANH 43% versus HHD 35% of
      patients received homologous blood) (P > 0.05). Heart rate did not change
      significantly in either group. In the ANH group mean arterial blood pressure
      (MAP) decreased after hemodilution (P < 0.05) while in the HHD group MAP did not
      change over time. Mean time required to perform ANH was 58 (46-62) min versus HHD
      16 (12-19) min (P < 0.05). Costs for ANH were $63.60 USD and for HHD $32.75 USD
      (labor costs not included). In orthopedic patients undergoing hip replacement
      with a predicted blood loss of about 1000 mL, HHD seems to be a simple as well as
      time- and cost-saving alternative for ANH.

PMID- 8988995
TI  - A modified thromboelastographic method for monitoring c7E3 Fab in heparinized
      patients.
AB  - The monoclonal antibody, c7E3 Fab, binds to the platelet surface fibrinogen
      receptor (GPIIb/IIIa), inhibiting platelet aggregation and clot retraction. We
      performed an in vitro study to assess the ability of a modification of the
      thromboelastograph (MTEG) to detect inhibition of clot strength by c7E3 Fab and
      its reversal with platelet-rich plasma (PRP). In the modified assay (MTEG),
      thrombin was added to whole blood (WB) and platelet-poor plasma (PPP) and the
      resultant maximum amplitude (MA) was measured, MAWB and MAPPP, respectively.
      Anticoagulated blood samples from 17 patients scheduled for cardiac surgery were
      collected for a dose response (Part I; n = 5) and c7E3 Fab reversal (Part II; n =
      12) study. Clot strength was reduced in a dose-dependent manner by c7E3 Fab.
      Ecteola cellulose effectively reversed the effect of heparin on the thrombin time
      and the addition of PRP significantly increased the MAWB (P < 0.0001) and MAWP
      PPP (P < 0.0001). Subtracting the MAPPP from MAWB significantly magnified the
      response of MA to the addition of c7E3 Fab (P = 0.002) and its reversal with PRP
      (P = 0.005). This in vitro study indicates that the MTEG is a responsive assay
      demonstrating that inhibition by the antiplatelet c7E3 Fab is reversible with
      PRP.

PMID- 8988996
TI  - Effects and interactions of nitrous oxide, myocardial ischemia, and reperfusion
      on left ventricular diastolic function.
AB  - The effects of nitrous oxide on left ventricular diastolic function and its
      potential interactions with ischemia-induced diastolic dysfunction have not been
      described. Accordingly, we investigated the effects of nitrous oxide in ischemic
      and remote nonischemic myocardium during baseline, 90 min severe low-flow
      myocardial ischemia (systolic bulge), and reperfusion in 11 open-chest dogs.
      Anesthesia was maintained with fentanyl infusion (2 micrograms.kg-1.min-1),
      animals were ventilated with 60% nitrogen in oxygen, and hemodynamic variables
      were recorded prior to and after the replacement of nitrogen by 60% nitrous
      oxide. During baseline, nitrous oxide moderately increased chamber stiffness (+
      10%), myocardial stiffness (+33%), and unstressed length (+4%) and decreased the
      peak lengthening rate (-10%). Moreover, nitrous oxide decreased regional
      contractility during baseline (-12% at apex, -8% at base) as well as in
      nonischemic myocardium during myocardial ischemia (-9%) and reperfusion (-8%).
      However, nitrous oxide did not modify ischemia-induced systolic or diastolic
      dysfunction in ischemic myocardium during ischemia and reperfusion. Myocardial
      ischemia (+45%) and reperfusion (+57%) were associated with an increase in
      myocardial stiffness of nonischemic myocardium regardless of the anesthetic
      technique used. This study is the first to demonstrate that in addition to its
      well established negative inotropic effect, nitrous oxide affects regional
      diastolic function.

PMID- 8988997
TI  - Decreased digital flow persists after the abatement of cocaine-induced
      hemodynamic stimulation.
AB  - This study determined whether the development of delayed ischemic sequelae due to
      cocaine use--after the return of arterial blood pressure (BP) and heart rate to
      near-baseline values--may be attributable to regional vasoconstriction which
      persists beyond the acute systemic hemodynamic response. Five cocaine-using
      volunteers received intravenous infusions of saline placebo and cocaine 0.50
      mg/kg several days apart in a double-blinded cross-over design. The intensity and
      duration of the cocaine-induced decrease in peripheral blood flow (as documented
      by laser Doppler flowmetry of the finger) were compared to the increases in BP
      (obtained with a Dinamap) and heart rate using paired t-test and repeated
      measures analysis of variance. A significant increase in BP and a significant
      decrease in finger flow were noted by the first time point (5 min). Within 15
      min, cocaine induced a 36% +/- 5% increase in BP and a 73% +/- 18% decline in
      finger flow (P < 0.05 for difference between percent change in BP and percent
      change in flow). Dinamap(systolic) and Dinamap(diastolic) returned to within 15%
      of baseline within 30 min, while finger flow remained more than 50% below
      baseline for the remainder of the 60-min study period (P < 0.05). Changes in
      heart rate paralleled those in BP. Except for isolated cases of documented
      coronary vasoconstriction in patients presenting with complications after cocaine
      use, this study is the first to document the persistence of cocaine-induced
      vasoconstriction of a sensitive vascular bed beyond the hypertensive response. It
      thus helps to explain the development of ischemic injury after cocaine use
      despite a stable rate-pressure product.

PMID- 8988998
TI  - Comparison of end-tidal and arterial carbon dioxide in infants using laryngeal
      mask airway and endotracheal tube.
AB  - The laryngeal mask airway (LMA) has become a popular tool for airway management
      in selected adult and pediatric patients undergoing routine surgical procedures.
      The relationship between end-tidal and arterial carbon dioxide during controlled
      ventilation via the LMA in infants under 10 kg has not been reported. After
      induction of general anesthesia, the LMA was placed in 12 healthy infants and
      mechanical ventilation initiated. After maintaining steady-state level of end
      tidal carbon dioxide (minimum 5 min), an arterial blood sample was obtained and
      end-tidal carbon dioxide level noted. The laryngeal mask was then removed, the
      trachea intubated, and mechanical ventilation resumed with initial ventilatory
      variables. After reaching a steady-state level of end-tidal carbon dioxide, a
      second arterial sample was obtained and end-tidal carbon dioxide level noted. The
      mean end-tidal carbon dioxide and arterial partial pressure of carbon dioxide
      obtained during ventilation were 42.2 +/- 7.9 and 47.1 +/- 11.0 (LMA) and 37.4 +/
      4.6 and 42.6 +/- 6.7 (endotracheal tube), respectively. Analysis of differences
      between partial pressure of carbon dioxide and end-tidal carbon dioxide using the
      Bland and Altman method revealed bias+/-precision of 4.9 +/- 3.9 and 5.3 +/- 3.2
      with ventilation via the laryngeal mask and endotracheal tube. Our data indicate
      that, while ventilating infants under 10 kg with LMA, end-tidal carbon dioxide is
      an accurate indicator of arterial partial pressure of carbon dioxide.

PMID- 8988999
TI  - Intramuscular atropine sulfate in children: comparison of injection sites.
AB  - In children undergoing inhaled induction of anesthesia with halothane who suffer
      bradycardia, submental glossal injection of atropine may result in more rapid
      onset of vagolysis than traditional intramuscular sites. We compared the
      intervals between injection and onset of heart rate acceleration (tHR increases)
      after intramuscular injection of atropine into the deltoid, vastus lateralis, and
      glossa in children between 1 mo and 10 yr of age scheduled for elective surgery.
      The tHR increases was determined by measuring the interval between atropine
      injection and the time point at which the slope of the heart rate curve initially
      became positive. To ensure that the drug had taken effect before surgical
      stimulation, heart rate observation was continued until it increased at least 5%
      above baseline with evidence of continuing acceleration. Anesthesia was induced
      in all subjects by mask with nitrous oxide and halothane. After tracheal
      intubation, constant inspired concentrations of the anesthetics were administered
      for 3 min. While heart rate was monitored, atropine (0.02 mg/kg) was injected
      into one of the three sites. Each patient's end-tidal anesthetic concentrations
      were recorded, and minimum alveolar anesthetic concentrations (MAC) were
      subsequently calculated and adjusted for age. The tHR increases was recorded and
      averaged for each group. The study groups did not differ by age, weight, end
      tidal anesthetic concentrations, age-adjusted MAC, or heart rate at the time
      atropine was administered. After submental glossal injection (n = 11), tHR
      increases increase was fastest (3.0 +/- 1.1 min) and was significantly faster
      than that found with deltoid injection (n = 16; 4.4 +/- 1.1 min) or vastus
      lateralis injection (n = 8; 6.4 +/- 2.4 min) (P < 0.05 compared with both). The
      tHR increases also differed significantly between the deltoid and the vastus
      lateralis (P < 0.05). We conclude that submental glossal injection of atropine
      results in a more rapid onset of vagolysis than injection at traditional
      intramuscular sites.

PMID- 8989000
TI  - Small-dose hypobaric lidocaine-fentanyl spinal anesthesia for short duration
      outpatient laparoscopy. I. A randomized comparison with conventional dose
      hyperbaric lidocaine.
AB  - A randomized, single-blind trial of two spinal anesthetic solutions for
      outpatient laparoscopy was conducted to compare intraoperative conditions and
      postoperative recovery. Thirty women (ASA physical status I and II) were assigned
      to one of two groups. Group I patients received a small-dose hypobaric solution
      of 1% lidocaine 25 mg made up to 3 mL by the addition of fentanyl 25 micrograms.
      Group II patients received a conventional-dose hyperbaric solution of 5%
      lidocaine 75 mg (in 7.5% dextrose) made up to 3 mL by the addition of 1.5 mL 10%
      dextrose. All patients received 500 mL of crystalloid preloading. Spinal
      anesthesia was performed at L2-3 or L3-4 with a 27-gauge Quincke point needle.
      Surgery commenced when the level of sensory anesthesia reached T-6.
      Intraoperative hypotension requiring treatment with ephedrine occurred in 54% of
      Group II patients but not in any Group I patients. Median (range) time for full
      motor recovery was 50 (0-95) min in Group I patients compared to 90 (50-120) min
      in Group II patients (P = 0.0005). Sensory recovery also occurred faster in Group
      I patients (100 +/- 22 min) compared with Group II patients (140 +/- 27 min, P =
      0.0001). Postoperative headache occurred in 38% of all patients and 70% of these
      were postural in nature. Oral analgesia was the only treatment required. Spinal
      anesthesia did not result in a significant incidence of postoperative backache.
      On follow-up, 96% said they found spinal needle insertion acceptable, 93% found
      surgery comfortable, and 90% said they would request spinal anesthesia for
      laparoscopy in future. Overall, this study found spinal anesthesia for outpatient
      laparoscopy to have high patient acceptance and a comparable complication rate to
      other studies. The small-dose hypobaric lidocaine-fentanyl technique has
      advantages over conventional-dose hyperbaric lidocaine of no hypotension and
      faster recovery.

PMID- 8989001
TI  - Small-dose hypobaric lidocaine-fentanyl spinal anesthesia for short duration
      outpatient laparoscopy. II. Optimal fentanyl dose.
AB  - We performed a double-blind, controlled trial to determine the optimal dose of
      intrathecal fentanyl in small-dose hypobaric lidocaine spinal anesthesia for
      outpatient laparoscopy. Sixty-four gynecological patients were randomized into
      three groups, receiving 0, 10, or 25 micrograms fentanyl added to 20 mg lidocaine
      and sterile water (total 3 mL). Administration was with 27-gauge Whitacre needles
      and patients sat upright until the block was > T-8. One patient in the 0
      microgram fentanyl group required general anesthesia 40 min after the start of
      surgery, leaving 21 patients per group. Three patients in each of the 0-microgram
      and 10-microgram fentanyl groups had mild discomfort with trocar insertion, or
      return of some sensation and felt discomfort or sutures toward the end of
      surgery. Shoulder-tip pain was less frequent in the 25-microgram than 0-microgram
      fentanyl group, 28% vs 67% (P < 0.0166). Intraoperative supplementation with
      alfentanil (+/- propofol) was needed less often in the 25-microgram than 0
      microgram fentanyl group, 43% vs 76% (P = 0.028). Recovery of sensation took
      longer in the 25-microgram than in the 0-microgram and 10-microgram fentanyl
      groups, 101 +/- 21 vs 84 +/- 20 and 87 +/- 18 min (P < 0.05), although motor
      recovery and discharge times were the same. Postoperative analgesia was needed
      earlier in the 0-microgram than in the 25-microgram fentanyl group, median 54 (13
      120) vs 87 (65-132) min (P < 0.05). Pruritus was the only side effect that
      occurred more often in the 10-microgram and 25-microgram groups than in the 0
      microgram fentanyl group, 62% and 67% vs 14% (P < 0.0166). One patient required
      an epidural blood patch for postdural puncture headache. Based on these results,
      we concluded that 25 micrograms intrathecal fentanyl is required when 20 mg
      lidocaine is used for hypobaric spinal anesthesia (SA) to ensure reliable,
      durable anesthesia, reduce shoulder-tip pain, and minimize the need for
      intraoperative supplementation. This dose provides longer postoperative analgesia
      and does not increase side effects apart from pruritus. SA with small-dose
      hypobaric lidocaine-fentanyl was found to be a satisfactory technique for
      outpatient laparoscopy, although postdural puncture headache can occur in some
      patients.

PMID- 8989002
TI  - Small-dose propofol by continuous infusion does not prevent postoperative
      vomiting in females undergoing outpatient laparoscopy.
AB  - This study was designed to test the hypothesis that there is a direct
      prophylactic antiemetic effect of small-dose propofol given by continuous
      infusion. Sixty female patients undergoing outpatient laparoscopy under general
      anesthesia were randomized to receive, in a double-blind fashion, either a bolus
      of 0.1 mg/kg followed by a constant infusion of 1 mg.kg-1.h-1 of propofol or an
      equivalent volume of 10% Intralipid (placebo) beginning 30 min before induction
      of anesthesia and continuing until discharge from Stage I postanesthesia care
      unit (PACU). Anesthesia was induced and maintained in a standard fashion in all
      patients. The number of emetic episodes before and after discharge from PACU,
      nausea scores (11-point numerical scale), and time to discharge were evaluated.
      No significant differences between Intralipid and propofol were found for any of
      the outcome variables tested. While small-dose propofol is an effective adjuvant
      in reducing chemotherapy-induced emesis, we were unable to demonstrate any
      beneficial effect of propofol in reducing postoperative nausea and vomiting when
      used as the sole prophylactic medication in this patient population. Propofol may
      have a synergistic effect when administered with other antiemetics, or the
      specific antiemetic effect of propofol, if it exists, may be dose-dependent and
      the dose used in this study was below the efficacy threshold.

PMID- 8989003
TI  - Cocaine screening of parturients without prenatal care: an evaluation of a rapid
      screening assay.
AB  - Illicit drugs are used widely by inner city patients in our society. Because
      cocaine ingestion can produce life-threatening arrhythmias and interact with
      anesthetic drugs, it is potentially useful for the anesthesiologist to know a
      high-risk patient's cocaine status before administering anesthesia. The commonly
      used methods to detect cocaine abuse, however, often require 1-3 days for
      laboratory processing. With these tests, anesthesiologists are unable to test for
      recent cocaine use in an emergency setting. A new rapid latex agglutination assay
      for urinary metabolites of cocaine (OnTrak Abuscreen; Roche Diagnostic Systems
      Inc., Branchburg, NJ) was compared with an assay used by many hospital
      laboratories. The prevalence of cocaine abuse in the group of unregistered
      parturients was found to be 68%, with the latex agglutination results exactly
      matching the hospital laboratory results (kappa = 1.0). A sensitive and specific
      method now exists that allows anesthesiologists to assess cocaine use rapidly, so
      that they can use this information when planning a patient's anesthetic.

PMID- 8989004
TI  - Percutaneous nonangiographic insertion of Hickman catheters in marrow transplant
      recipients by anesthesiologists and intensivists.
AB  - Long-term central venous lines for chronic hemoaccess are usually inserted in the
      operating theater under local or general anesthesia or in interventional
      radiology suites using fluoroscopic technique. In a prospective study we
      determined the feasibility of percutaneous insertion of Hickman catheters without
      fluoroscopic control by anesthesiologists and intensivists in the setting of an
      intensive care unit. Fifty-four Hickman catheters were placed in 53 consecutive
      patients with hematological disorders and/or neoplastic diseases undergoing
      allogeneic or autologous bone marrow transplantation (BMT) or buffy coat therapy.
      There were no major complications. The mean time for insertion was 35 min. The
      median life span of catheters was 70 days (range 3-214). Twenty-six catheters
      were electively removed; six remained functioning in situ at the end of the
      study. For 3333 catheter days (1471 days in hospital and 1862 days at domiciliary
      care), six catheters were removed because of mechanical complications
      (inadvertent dislodgement, leak, secondary migration) and 14 because of suspected
      or documented infection. We conclude that percutaneous nonangiographic insertion
      of Hickman catheters by anesthesiologists minimizes technical expenditure and is
      at least as effective as surgical or radiological techniques. The rate of
      clinically important complications is acceptable.

PMID- 8989005
TI  - Pharmacokinetics of the enantiomers of mepivacaine after intravenous
      administration of the racemate in volunteers.
AB  - The pharmacokinetics of R(-)-mepivacaine and S(+)-mepivacaine were investigated
      in 10 healthy volunteers. The volunteers received racemic mepivacaine,
      hydrochloride (dose 60 mg) via a 10-min intravenous infusion. Blood samples were
      collected at gradually increasing intervals until 8 h after the start of the
      infusion. Plasma concentrations of the enantiomers were determined with a
      stereoselective high-performance liquid chromatographic (HPLC) method. Unbound
      fractions of the enantiomers were determined using equilibrium dialysis. The
      unbound fraction of R(-)-mepivacaine (mean +/- SD: 35.6% +/- 4.5%) was larger (P
      < 0.0001) than that of S(+)-mepivacaine (25.1% +/- 4.6%). The total plasma
      clearance and steady-state volume of distribution of R(-)-mepivacaine, based on
      total plasma concentrations (total plasma clearance [CL] = 0.79 +/- 0.12 L/min;
      volume of distribution at steady state [VSS] = 103 +/- 14 L) as well as on
      unbound plasma concentrations (plasma clearance of unbound drug [CLu] = 2.24 +/-
      0.30 L/min; volume of distribution of unbound drug at steady state [Vuss] = 290
      +/- 32 L), were larger (P < 0.0001) than those of S(+)-mepivacaine (CL = 0.35 +/-
      0.06 L/min; Vss = 57 +/- 7 L; CLu = 1.43 +/- 0.24 L/ min; Vuss = 232 +/- 30 L).
      The terminal half-life (t1/2,Z) and mean residence time (MRT) of R(-)-mepivacaine
      (t1/2,Z = 113 +/- 17 min; MRT = 131 +/- 15 min) were shorter than those of S(+)
      mepivacaine (t1/2,Z = 123 +/- 20 min, P < 0.02; MRT = 165 +/- 24 min, P <
      0.0001). This study demonstrated a marked difference in the pharmacokinetics of
      the enantiomers of mepivacaine. The stereoselectivity can be partially explained
      by a difference in the plasma protein binding of the enantiomers.

PMID- 8989006
TI  - Antinociceptive effect of bupivacaine encapsulated in poly(D,L)-lactide-co
      glycolide microspheres in the acute inflammatory pain model of carrageenin
      injected rats.
AB  - Encapsulating bupivacaine in poly(D,L)-lactide-coglycolide microspheres may
      prolong analgesia and diminish systemic toxicity. The antinociceptive effect of
      bupivacaine-loaded microspheres (1, 2.5, and 5 mg) and plain bupivacaine
      solutions (1, 2.5, and 5 mg) were compared using the vocalization threshold to
      paw pressure test (VTPP) in rats. Local anesthetic solutions were injected
      subcutaneously in the plantar hindpaw. First, the biological inactivity of the
      vehicle and drug-free microspheres (DFM) was evaluated in normal (n = 8) or
      carrageenin-injected rats (n = 24). Second, onset of antinociception was
      evaluated in normal rats (n = 16). We then evaluated the duration of
      antinociception induced by the different local anesthetic solutions in
      carrageenin-injected rats (n = 56). Neither the vehicle nor the DFM induced any
      modification of the VTPP. Onset of antinociception was 5 min for all local
      anesthetic solutions. Duration of antinociception was 60 min with plain
      bupivacaine (1 mg) and increased to 90, 120, and 180 min, respectively, for the
      different doses of bupivacaine-loaded microspheres (1, 2.5, and 5 mg). Larger
      doses of plain bupivacaine (2.5 and 5 mg) induced systemic toxicity. The
      encapsulation of bupivacaine in microspheres induced a dose-dependent increase in
      duration of antinociception as compared with plain bupivacaine.

PMID- 8989007
TI  - Densities of dextrose-free intrathecal local anesthetics, opioids, and
      combinations measured at 37 degrees C.
AB  - Dextrose-free anesthetic medications are commonly used to provide subarachnoid
      anesthesia and analgesia. Hypobaricity has been proposed as a mechanism to
      explain postural effects on the extent of sensory block produced by these drugs.
      Densities of dextrose-free solutions of local anesthetics and opioids, and
      commonly used anesthetic/opioid mixtures were determined at 37.00 degrees C for
      comparison with the density of human cerebrospinal fluid (CSF). Measurements
      accurate to 0.00001 g/mL were performed using a mechanical oscillation resonance
      frequency density meter. All undiluted solutions tested are hypobaric relative to
      human lumbar CSF with the exception of lidocaine 1.5% and 2.0% with epinephrine
      1:200,000. All mixtures of local anesthetics and opioids tested are hypobaric. We
      observed good agreement between measured densities and calculated weighted
      average densities of anesthetic mixtures. While the influence of baricity on the
      clinical effects of dextrose-free intrathecal anesthetics remains controversial,
      attempts to attribute postural effects to the baricity of these drugs requires
      establishment of accurate density values. These density data may facilitate
      elucidation of the mechanisms underlying the behavior of dextrose-free
      intrathecal anesthetics.

PMID- 8989008
TI  - Effects of epidural and intravenous buprenorphine on halothane minimum alveolar
      anesthetic concentration and hemodynamic responses.
AB  - There is limited information regarding the effects of epidural or intravenous
      (i.v.) buprenorphine on minimum alveolar anesthetic concentration (MAC) of
      volatile anesthetic and hemodynamic responses to tracheal intubation and surgical
      incision. This study was conducted to find the effects of i.v. and epidural
      buprenorphine required for postoperative pain relief on halothane MAC and
      hemodynamic responses to tracheal intubation and surgical incision in 126 female
      patients. Patients were randomly assigned to the four groups: Group I received
      i.v. and epidural saline as a control; Group II was given buprenorphine 4
      micrograms/kg i.v.; and Groups III and IV received buprenorphine 2 and 4
      micrograms/kg epidurally, respectively. Groups II-IV were divided into the two
      subgroups according to the timing of administration, either at induction of
      anesthesia in the operating room (OR) (OR group) or 90 min before anesthetic
      induction in the ward (Ward group). Anesthesia was induced with only halothane in
      oxygen, and the trachea was intubated without other drugs. Halothane MAC was
      determined by logistic regression analysis and the Dixon up-and-down method.
      Halothane MAC in the seven study groups was as follows: 0.75% +/- 0.05% (mean +/-
      SE) in Group I; 0.49% +/- 0.03% and 0.59% +/- 0.04%, respectively, in Groups II
      OR and Ward; 0.65% +/- 0.003% and 0.49% +/- 0.07%, respectively, in Groups III OR
      and Ward; and 0.51% +/- 0.07% and 0.37% +/- 0.02%, respectively, in Groups IV OR
      and Ward. Halothane MAC decreased significantly (P < 0.05) in groups that
      received buprenorphine except Group III-OR compared with Group I. Systolic blood
      pressure did not change significantly in Groups II-OR and IV-OR after tracheal
      intubation and in Group III-Ward and IV-Ward after surgical incision but
      increased significantly (P < 0.05) in the remaining groups in response to noxious
      stimuli. Heart rate responses to tracheal intubation and surgical incision were
      similar to those in systolic blood pressure. These results indicate that
      preanesthetic administration of epidural or IV buprenorphine required for
      postoperative analgesia reduces halothane MAC and attenuates hemodynamic
      responses to tracheal intubation and surgical incision according to the dose,
      route, and timing of administration.

PMID- 8989009
TI  - Prevention of spinal anesthesia-induced hypotension in the elderly: comparison
      between preanesthetic administration of crystalloids, colloids, and no
      prehydration.
AB  - The practice of routinely prehydrating patients by infusing a crystalloid or
      colloid solution (up to 1.0 L/70 kg) for prevention of spinal anesthesia-induced
      hypotension has been challenged recently, after several reports of failure to
      demonstrate its efficacy in young women. We compared the incidence and frequency
      of hypotension and vasopressor therapy after spinal anesthesia and no
      prehydration with crystalloid and colloid prehydration in elderly patients.
      Eighty-five ASA grade I or II patients (aged 60-89 yr) for elective total hip
      replacement were randomized to receive 500 mL crystalloid solution (Hartmanns, n
      = 29), 500 mL colloid (Haemaccel, n = 28), or no prehydration (n = 28) over 10
      min prior to spinal anesthesia. Hypotension was defined as a 30% decrease from
      baseline systolic blood pressure (BP) or systolic < 90 mm Hg, and was treated
      with ephedrine 3-mg boluses. Although absolute systolic BP readings were
      significantly higher in the colloid group between 6 and 30 min (P < 0.05), the
      incidence of hypotension was not significantly different between the groups. The
      incidence of ephedrine use, incidence of nausea/vomiting, and median total dose
      of ephedrine were similar in all groups. We conclude that, in elderly patients
      undergoing elective procedures, withholding prehydration is not associated with
      any greater degree of hypotension or need for vasopressor therapy compared with
      crystalloid or colloid prehydration.

PMID- 8989010
TI  - Prevention of hypotension during spinal anesthesia: a comparison of intravascular
      administration of hetastarch versus lactated Ringer's solution.
AB  - This study was designed to compare the efficacy of 6% hetastarch to that of
      crystalloid administration in reducing the incidence and severity of hypotension
      during spinal anesthesia. Forty ASA grade I patients scheduled for postpartum
      tubal ligations under spinal anesthesia were randomly allocated to receive either
      500 mL of hetastarch solution or 1000 mL of lactated Ringer's solution prior to
      spinal anesthesia. Spinal anesthesia was managed identically in both groups by
      anesthesiologists who were unaware of the type of fluid administered. The
      incidence of hypotension was 11 of 21 (52%) in the lactated Ringer's solution
      group and 3 of 19 (16%) in the hetastarch group. The difference in the incidence
      of hypotension was significant (P < 0.05). The requirement of 5-mg bolus doses of
      ephedrine to maintain systolic arterial blood pressure > 75% of baseline was
      significantly greater in the lactated Ringer's group than in the hetastarch group
      (15 vs 4, P < 0.05). We conclude that an intravenous infusion of 500 mL of 6%
      hetastarch solution is more effective than 1000 mL lactated Ringer's solution in
      attenuating spinal anesthesia induced hypotension in women undergoing postpartum
      tubal ligation.

PMID- 8989011
TI  - Differential sensory block after spinal bupivacaine in volunteers.
AB  - We performed this study to determine whether differential sensory block to touch,
      pinprick, and cold after spinal bupivacaine could be used to predict the
      dermatomal level of block to transcutaneous electrical stimulation (TES)
      equivalent to surgical stimulation, onset of tourniquet pain, or magnitude of
      hemodynamic depression. Eight subjects per group were randomized to receive 3.75,
      7.5, or 11.25 mg of 0.75% bupivacaine with 8.25% dextrose in a double-blind
      fashion. Sensory block was assessed with touch, pinprick, cold, TES at T-12, L-2,
      S-1, and thigh tourniquet pain. Differential extent of sensory block to touch,
      pinprick, and cold occurred at the time of offset of tolerance to TES (P < 0.03)
      and at the time of tourniquet pain (P < 0.05). However, the extent of
      differential sensory block to touch, pinprick, and cold varied up to 10
      dermatomes (2 SD) cephalad to block to TES and up to 7 dermatomes (2 SD) cephalad
      to the thigh tourniquet at the time of intolerable tourniquet pain. Sensory block
      to cold did not correlate with hemodynamic depression. Differential sensory block
      occurs after bupivacaine spinal anesthesia, but is a poor predictor for surgical
      anesthesia, tourniquet pain, and hemodynamic depression.

PMID- 8989012
TI  - Regional brain activity changes associated with fentanyl analgesia elucidated by
      positron emission tomography.
AB  - Recent positron emission tomography (PET) studies have demonstrated areas of pain
      processing in the human brain. Given the inhibitory effects of opioids on
      neuronal activity, we predicted that fentanyl's analgesic effects would be
      associated with suppression of pain-evoked responses in these distinct brain
      areas. To test this, PET was used to measure cerebral blood flow responses, as
      reflections of regional neuronal activity, to painful and nonpainful thermal
      stimuli both in the absence and presence of fentanyl in humans. During each PET
      scan in nine healthy volunteers a tonic heat source was placed against the
      subject's left forearm, delivering a preset temperature of either 40 degrees C
      (nonpainful) or 47-48 degrees C (painful). Subjects underwent eight blood flow
      studies, each consisting of 50 mCi [15O]water injection and a PET scan. The first
      four studies were performed during placebo administration in the stimulus
      sequence: nonpainful, painful, painful, nonpainful. This sequence was then
      repeated during intravenous (i.v.) administration of fentanyl 1.5 micrograms/kg
      [corrected]. Significant differences in regional cerebral blood flow (rCBF)
      between the placebo and the fentanyl conditions during nonpainful and painful
      stimuli were identified using statistical parametric mapping. It was found that
      pain increased rCBF in the anterior cingulate, ipsilateral thalamus, prefrontal
      cortex, and contralateral supplementary motor area. Fentanyl increased rCBF in
      the anterior cingulate and contralateral motor cortices, and decreased rCBF in
      the thalamus (bilaterally) and posterior cingulate during both stimuli. During
      combined pain stimulation and fentanyl administration, fentanyl significantly
      augmented pain-related rCBF increases in the supplementary motor area and
      prefrontal cortex. This activation pattern was associated with decreased pain
      perception, as measured on a visual analog scale. In contrast to our hypothesis,
      these data indicate that fentanyl analgesia involves augmentation of pain-evoked
      cerebral responses in certain areas, as well as both activation and inhibition in
      other brain regions unresponsive to pain stimulation alone.

PMID- 8989013
TI  - Changes in cerebral hemodynamics after a single dose of clonidine in severely
      head-injured patients.
AB  - alpha 2-Adrenergic agonists induce cerebral vasoconstriction, reduce intracranial
      pressure (ICP) in experimental animals and may be useful in the hemodynamic
      management of head-injured patients. We studied the effects of the alpha 2
      agonist clonidine on the cerebral circulation in 12 head-injured patients
      (Glasgow Coma Scale score < 8). Middle cerebral artery flow velocity (MCAV), ICP,
      mean arterial pressure (MAP), and cerebral perfusion pressure (CPP), were
      continuously recorded before (T0), at the end (T1), and 30 min after (T2) a 10
      min intravenous (i.v.) infusion of 2.5 micrograms/kg clonidine. The cerebral
      arteriovenous oxygen content difference (AVDO2) and Paco2 were sequentially
      obtained. ICP, Paco2, AVDO2, and MCAV did not change after clonidine
      administration. In contrast, MAP and CPP decreased (P < 0.05 and P < 0.05,
      respectively, at T1 and T2). Three subjects displayed a transient increase in ICP
      (> 10 mm Hg) at T1; this increase was concomitant with the decrease in MAP.
      Clonidine administered as an i.v. infusion may induce a critical but transient
      increase in ICP in some severely head-injured patients. This effect may result
      from cerebral autoregulatory vasodilation and increased cerebral blood volume as
      a response to the hypotensive effects of clonidine.

PMID- 8989014
TI  - Differential effects of two intraventricularly injected alpha 2 agonists, ST-91
      and dexmedetomidine, on electroencephalogram, feeding, and electromyogram.
AB  - Central alpha 2 agonists induce feeding in animals, electroencephalographic (EEG)
      synchronization, and sedation. Recent observations suggest that the
      investigational compound ST-91 and dexmedetomidine (DMET) may interact with
      distinct alpha 2 subclasses at spinal sites. We examined these drugs in brain. To
      accomplish these aims, ST-91, DMET, or methoxamine (METH), an alpha 1 agonist,
      were administered into the cerebral ventricles of unanesthetized rats prepared
      with chronic intracerebroventricular (ICVT) cannulae and cortical EEG electrodes.
      Behavior, EEG, electromyography (EMG), and feeding were assessed. We found that
      DMET resulted in dose-dependent (1-32 nmol) sedation, EEG synchronization, and a
      reduced gastrocnemeus EMG, while ST-91 (up to 153 nmol) had no effect. In
      contrast, ST-91 (1-153 nmol) resulted in a dose-dependent evocation of feeding,
      while the effects of DMET on feeding, if any, were obscured by the sedation. All
      effects were antagonized in a dose-dependent fashion by ICVT yohimbine (an alpha
      2 antagonist). ICVT atipamezole (an alpha 2 antagonist), but not prazosin (an
      alpha 1 antagonist), reversed the effects of DMET. With ST-91, both atipamezole
      and prazosin had modest, but significant, antagonistic effects. ICVT METH had no
      effect. The differential physiological actions of these two
      intracerebroventricularly injected drugs, in concert with previous
      pharmacological studies, suggest two distinct subclasses of yohimbine-sensitive
      alpha 2 adrenergic receptors in the brain.

PMID- 8989015
TI  - Intraventricular dexmedetomidine decreases cerebral blood flow during normoxia
      and hypoxia in dogs.
AB  - We tested the hypothesis that a centrally administered alpha 2-receptor agonist
      could alter the cerebrovascular response to hypoxia, without evidence of systemic
      absorption of the drug. Beagle dogs were anesthetized with 1.4% isoflurane and
      exposed to hypoxic hypoxia (Pao2 approximately 22 mm Hg) before and after
      ventricular-cisternal perfusion with mock cerebrospinal fluid (CSF group, n = 5)
      or dexmedetomidine (100 micrograms/mL; total dose 300 micrograms; DEX group, n =
      6). Cerebral perfusion pressure, Paco2 and arterial oxygen content were
      controlled and regional cerebral blood flow (CBF; microspheres) and global
      cerebral metabolic rate for oxygen consumption (CMRO2) were measured. In another
      group (n = 5), drug distribution under the experimental conditions was assessed
      by 3H-clonidine administered by ventricular-cisternal perfusion. In the mock CSF
      group, flow to the cerebral hemispheres increased during hypoxia under baseline
      conditions and after CSF infusion: 66 +/- 8 to 170 +/- 15 mL.min-1.100 g-1 (265%
      +/- 24% of baseline value), 83 +/- 9 to 154 +/- 14 mL.min-1.100 g-1 (201% +/- 54%
      of post-CSF infusion value). DEX decreased normoxic flow in the cerebral
      hemispheres from 76 +/- 6 to 44 +/- 4 ml.min-1.100 g-1 with decreases in other
      regions of similar magnitude. After DEX, the absolute flow in all regions during
      hypoxia was 52%-55% of that prior to DEX (P < 0.05). However, because DEX also
      decreased normoxic CBF, the percent increase in flow during hypoxia was similar
      before and after DEX. CMRO2 was not affected by hypoxia prior to DEX. However,
      after DEX, hypoxia caused a marked reduction in cerebral oxygen delivery (5.2 +/-
      1.0 vs 13.7 +/- 2.3 ml.min-1.100 g-1 for the CSF group) and CMRO2 (2.5 +/- 0.6 vs
      3.9 +/- 0.6 ml.min-1.100 g-1). Regional accumulation of intraventricularly
      administered 3H-clonidine was greatest in periventricular brain structures (e.g.,
      caudate nucleus, dorsal brainstem), and the concentration in the cerebral cortex
      was approximately 1% of the concentration in the ipsilateral caudate nucleus. We
      conclude that centrally administered DEX reduces CBF during normoxia and prevents
      adequate oxygen delivery during hypoxia. The mechanism of DEX-induced CBF
      reduction is not metabolically mediated, since CMRO2 is maintained at control
      values during normoxia despite the significant blood flow reduction. We believe
      that the reduction in CMRO2 during hypoxia in DEX-treated dogs is the result of a
      reduction of oxygen delivery rather than the underlying mechanism for the
      observed reduction in CBF during hypoxia.

PMID- 8989016
TI  - The effects of reversal of neuromuscular blockade on autonomic control in the
      perioperative period.
AB  - Impaired parasympathetic control of heart rate is associated with increased
      incidence of cardiac dysrhythmias and ischemia. Anticholinergic drugs suppress
      parasympathetic control and could be detrimental in the early postoperative
      period in high-risk patients. In this double-blind randomized trial, 30 ASA
      physical status I and II patients undergoing minor surgery received either
      atropine 20 micrograms/kg and neostigmine 50 micrograms/kg (Group A),
      glycopyrrolate 8 micrograms/kg and neostigmine 50 micrograms/kg (Group G), or
      placebo (Group P) for reversal of neuromuscular blockade. Two indices of
      parasympathetic modulation of heart rate, spontaneous baroreflex sensitivity, and
      high-frequency heart rate variability, were assessed. At 2 h after reversal,
      Group A showed persisting impairment of baroreflex sensitivity with respect to
      Group P (7.12 +/- 0.86 vs 12.71 +/- 1.38 ms/mm Hg, P = 0.022) as well as
      decreased high-frequency heart rate variability (280.8 +/- 30.1 vs 569.2 +/-
      115.2 ms2/Hz, P = 0.015). Groups A and G showed a borderline decrease in
      normalized high-frequency variability at 2 h (P = 0.05 for Groups A and G versus
      Group P). Anticholinergic drugs with neostigmine cause impairment of
      parasympathetic control of heart rate which persists into the early postoperative
      period. The effects of glycopyrrolate appear to be of shorter duration; this drug
      may thus be preferable in patients at risk of cardiovascular complications.

PMID- 8989017
TI  - The duration of impairment of autonomic control after anticholinergic drug
      administration in humans.
AB  - Impaired parasympathetic control of heart rate is associated with increased
      incidence of cardiac dysrhythmias and ischemia. Anticholinergic drugs, commonly
      administered during reversal of neuromuscular blockade, suppress parasympathetic
      control in the early postoperative period. This could potentially be detrimental
      in patients at risk of cardiovascular complications. The duration of
      parasympathetic impairment by two anticholinergic drugs were compared in this
      double-blind randomized cross-over study. Fourteen healthy volunteers received a
      single intravenous injection of atropine 20 micrograms/kg or glycopyrrolate 8
      micrograms/kg during two different study sessions. The methods of spontaneous
      baroreflex analysis and spectral analysis of heart rate variability generated
      indices of beat-by-beat parasympathetic modulation of heart rate. Both drugs
      resulted in a marked decrease in baroreflex sensitivity and high-frequency heart
      rate variability. The times to return to baseline values were approximately
      doubled after atropine compared to glycopyrrolate (177 +/- 22 vs 82 +/- 8 min for
      baroreflex sensitivity, 212 +/- 16 vs 111 +/- 14 min for high-frequency power,
      and 171 +/- 18 vs 95 +/- 18 min for high-frequency power normalized to total
      power; P < 0.01 for all variables). Atropine leads to more prolonged impairment
      of parasympathetic control than equipotent doses of glycopyrrolate, and its use
      may thus be less desirable in high-risk patients in the early postoperative
      period.

PMID- 8989019
TI  - Acetaminophen predisposes to renal and hepatic injury from compound A in the
      fasting rat.
AB  - Results of previous studies of Compound A, a degradation product of sevoflurane,
      suggested that decreases in glutathione stores may increase potential Compound A
      nephrotoxicity. By depleting these stores, fasting and various drugs may augment
      such nephrotoxicity. To test this possibility, we pretreated fasted Fisher rats
      with intraperitoneal 0 (vehicle only), 250, 500, or 1000 mg/kg of acetaminophen,
      a commonly used drug that depletes glutathione stores. After pretreatment, we
      administered Compound A for 3 h at concentrations ranging from 0 to 200 ppm. The
      larger doses of acetaminophen predisposed to greater renal and hepatic injury.
      For example, at 100 ppm Compound A, no rats had renal cortical injury when given
      vehicle only or 250 mg/kg acetaminophen, but 90% (9 of 10 rats) had injury at 500
      mg/kg and 100% (13 of 13) at 1000 mg/kg. Similarly, at 100 ppm Compound A,
      hepatic injury was not evident with vehicle only or 250 mg/kg, but occurred in
      30% of rats at 500 mg/kg, and in 69% at 1000 mg/kg. Given the considerable
      differences between humans and rats, and given the large doses of acetaminophen
      required, the clinical relevance of these findings is unclear. If clinically
      relevant, circumstances producing glutathione depletion (e.g., ingestion of drugs
      such as acetaminophen, or nutritional deficiencies) may predispose to renal or
      hepatic injury from Compound A in patients given sevoflurane at low fresh gas
      flow rates.

PMID- 8989018
TI  - Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers.
AB  - Present package labeling for sevoflurane recommends the use of fresh gas flow
      rates of 2 L/min or more when delivering anesthesia with sevoflurane. This
      recommendation resulted from a concern about the potential nephrotoxicity of a
      degradation product of sevoflurane, "Compound A," produced by the action of
      carbon dioxide absorbents on sevoflurane. To assess the adequacy of this
      recommendation, we compared the nephrotoxicity of 8 h of 1.25 minimum alveolar
      anesthetic concentration (MAC) sevoflurane (n = 10) versus desflurane (n = 9) in
      fluid-restricted (i.e., nothing by mouth overnight) volunteers when the
      anesthetic was given in a standard circle absorber anesthetic system at 2 L/min.
      Subjects were tested for markers of renal injury (urinary albumin, glucose, alpha
      glutathione-S-transferase [GST], and pi-GST; and serum creatinine and blood urea
      nitrogen [BUN]) before and 1, 2, 3, and/or 5-7 days after anesthesia. Desflurane
      did not produce renal injury. Rebreathing of sevoflurane produced average
      inspired concentrations of Compound A of 41 +/- 3 ppm (mean +/- SD). Sevoflurane
      was associated with transient injury to: 1) the glomerulus, as revealed by
      postanesthetic albuminuria; 2) the proximal tubule, as revealed by postanesthetic
      glucosuria and increased urinary alpha-GST; and 3) the distal tubule, as revealed
      by postanesthetic increased urinary pi-GST. These effects varied greatly (e.g.,
      on postanesthesia Day 3, the 24-h albumin excretion was < 0.03 g (normal) for one
      volunteer; 0.03-1 g for five others; 1-2 g for two others; 2.1 g for one
      volunteer; and 4.4 g for another volunteer). Neither anesthetic affected serum
      creatinine or BUN, nor changed the ability of the kidney to concentrate urine in
      response to vasopressin, 5 U/70 kg subcutaneously (i.e., these measures failed to
      reveal the injury produced). In addition, sevoflurane, but not desflurane, caused
      small postanesthetic increases in serum alanine aminotransferase (ALT),
      suggesting mild, transient hepatic injury.

PMID- 8989021
TI  - Comparison of tests for detecting leaks in the low-pressure system of anesthesia
      gas machines.
AB  - Small leaks in the low-pressure system (LPS) of the anesthesia gas machine can
      cause hypoxia or patient awareness. We sought to determine the relative
      sensitivities of the various tests recommended for detecting LPS leaks before
      anesthesia. Special adapters were fashioned to create leaks of six different
      sizes in the LPS that were equivalent to the following: a single 25-, 22-, 20-,
      or 15-gauge needle, two 15-gauge needles, or a 2.5-mm endotracheal tube
      connector. With each leak condition, five different leak tests were performed on
      three each of the following machines: Ohmeda Modulus I, Ohmeda Modulus II-Plus,
      and North American Drager Narkomed (2A, 3 and 4), for a total of 54 leaks to be
      detected for each leak test (3 x 3 x 6). The number of leaks detected with each
      test was compared by Fisher's exact test, P < 0.05 being considered significant.
      Only the negative pressure leak test detected all 54 leaks, a significant
      difference from the positive pressure test, which detected the least number of
      leaks, 28 (P < 0.05). Some leak tests are more suitable for specific anesthesia
      machines. Adoption of the negative pressure test as a universal LPS leak test may
      prevent the risks associated with using the wrong test for the particular
      anesthesia machine: hypoxic gas or patient awareness.

PMID- 8989020
TI  - Biotransformation of halothane, enflurane, isoflurane, and desflurane to
      trifluoroacetylated liver proteins: association between protein acylation and
      hepatic injury.
AB  - In susceptible patients, halothane, enflurane, isoflurane, and desflurane can
      produce severe hepatic injury by an immune response directed against reactive
      anesthetic metabolites covalently bound to hepatic proteins. The incidence of
      hepatotoxicity appears to directly correlate with anesthetic metabolism catalyzed
      by cytochrome P450 2E1 to trifluoroacetylated hepatic proteins. In the present
      study, we examined whether the extent of acylation of hepatic proteins in rats by
      halothane, enflurane, isoflurane, and desflurane correlated with reported
      relative rates of metabolism. After pretreatment with the P450 2E1 inducer
      isoniazid, five groups of 10 rats breathed 1.25 minimum alveolar anesthetic
      concentration (MAC) of halothane, enflurane, isoflurane, or desflurane in oxygen,
      or oxygen alone, each for 8 h. Immunochemical analysis of livers harvested 18 h
      after anesthetic exposure showed tissue acylation (greatest to least) after
      exposure to halothane, enflurane, or isoflurane. Reactivity was not different
      between isoflurane as compared to desflurane or oxygen alone. An enzyme-linked
      immunosorbent assay showed halothane reactivity was significantly greater than
      that of enflurane, isoflurane, desflurane, or oxygen, and that enflurane
      reactivity was significantly greater than desflurane or oxygen. Sera from
      patients with a clinical diagnosis of halothane hepatitis showed antibody
      reactivity against hepatic proteins from rats exposed to halothane or enflurane.
      No reactivity was detected in rats exposed to isoflurane, desflurane, or oxygen
      alone. These results indicate that production of acylated proteins may be an
      important mediator of anesthetic-induced hepatotoxicity.

PMID- 8989022
TI  - Electroencephalographic bispectral index correlates with intraoperative recall
      and depth of propofol-induced sedation.
AB  - The bispectral (BIS) index and 95% spectral edge frequency (SEF) of the
      electroencephalograph (EEG) have been used to study the anesthetic and sedative
      effects of intravenously (i.v.) administered drugs. This prospective study was
      designed to evaluate the effectiveness of the BIS index and 95% SEF for assessing
      the level of propofol-induced sedation and amnesia during regional anesthesia.
      Ten consenting adult patients undergoing surgery with regional anesthesia were
      administered propofol in increments of 10-20 mg i.v., every 5-10 min until they
      became unresponsive to tactile stimulation (i.e., mild prodding or shaking). The
      BIS index and 95% SEF were continuously recorded from a bifrontal montage (Fp1-Cz
      and Fp2-Cz) using the Aspect B500 monitor. The depth of sedation was assessed
      clinically at 5- to 10-min intervals using the observer's assessment of
      alertness/sedation (OAA/S) scale, with 1 = no response to tactile stimulation to
      5 = wide awake. Each patient was shown a picture of an animal (cat) prior to
      administration of an initial dose of propofol, 40 mg i.v.. Subsequently, patients
      were administered intermittent bolus doses of propofol, 10-20 mg i.v., and shown
      different pictures upon achieving OAA/S scores of 4, 3, and 2 during the onset of
      and recovery from propofol-induced sedation. Picture recall was tested upon
      arrival of the patient in the postanesthesia care unit (PACU). Of the two EEG
      variables studied, the BIS index exhibited a better correlation with the OAA/S
      scores during both the onset (Spearman's rho = 0.744) and recovery (Spearman's
      rho = 0.705) phases of propofol-induced sedation. With the increasing depth of
      sedation, there was a progressive decrease in the BIS index (OAA/S score of 5,
      BIS = 94.5 +/- 2.9; 4, 93.3 +/- 3.3; 3, 89 +/- 6.1; 2, 80.1 +/- 8.7; 1, 75.6 +/-
      7.5; mean +/- SD). Conversely, there was a progressive increase in the BIS value
      during recovery from propofol sedation (OAA/S score of 1, BIS = 75.6 +/- 7.5; 2,
      82.4 +/- 10.5; 3, 84.9 +/- 5.9; 4, 93.8 +/- 0.8). Although the changes in the 95%
      SEF values were less consistent during the onset phase, this EEG variable
      increased from 16.4 +/- 5.0 to 19.3 +/- 5.6 as the OAA/S score increased from 1
      to 4 during the recovery phase. Patient recall of the intraoperative pictures
      decreased with increasing depth of sedation and decreasing BIS values (OAA/S:%
      BIS:% recall = 5:94.5 +/- 2.9:100%; 4:93.4 +/- 3:63%; 3:87.3 +/- 6.1:40%; 2:80.8
      +/- 8.3:0%; 1:75.6 +/- 7.5:0%). The BIS index appears to be a useful variable for
      assessing the depth of propofol-induced sedation. Increasing depth of sedation
      was associated with a significant decrease in intraoperative picture recall.

PMID- 8989023
TI  - Inhibitory effect of the intravenous anesthetic, ketamine, on rat mesangial cell
      proliferation.
AB  - We studied the effects of ketamine and propofol on rat cultured mesangial cell
      (MC) proliferation. The 72-h exposure to ketamine (1-100 microM) inhibited
      [3H]thymidine incorporation into the MC in a concentration-dependent manner.
      Propofol, however, was not effective at inhibition of MC proliferation at doses
      from 1 to 100 microM. Ketamine also decreased the cell number at clinically
      relevant concentrations and increased adenosine 3',5'-cyclic monophosphate (cAMP)
      levels in MC. We also studied the effects of ketamine on cytokine-induced
      [3H]thymidine incorporation into the cells. Ketamine decreased the tumor necrosis
      factor-alpha (TNF-alpha)-, interleukin 1 (IL-1)-, and interleukin 6 (IL-6)
      induced [3H]thymidine incorporation into the cells. It also decreased angiotensin
      II (Ag II)-induced [3H]thymidine incorporation. These results suggest that
      ketamine has inhibitory effects on MC proliferation, but that propofol does not.
      Because ketamine inhibits TNF-alpha-, IL-1-, and IL-6-induced MC proliferation,
      it may be useful in suppressing the cell growth clinically.

PMID- 8989024
TI  - Subhypnotic doses of propofol do not possess antidopaminergic properties.
AB  - In order to investigate the possible interactions of propofol with the
      dopaminergic system, a prospective, randomized, double-blind, placebo-controlled
      study was performed on the profile of prolactin secretion, since prolactin blood
      levels are known to increase when dopaminergic receptors are blocked. Ten fasting
      female patients scheduled to receive cancer chemotherapy were allocated to
      receive either propofol at a rate of 1 mg.kg-1.h-1 or Intralipid 0.1 ml.kg-1.h-1.
      The study included two consecutive chemotherapy cycles; each patient received in
      a random order propofol or Intralipid. The infusions were started 4 h prior to
      induction of chemotherapy; prolactin blood levels were determined at time 0, 30,
      60, 120, and 240 min (end of the study period). The basal prolactin blood levels
      were 14.2 +/- 4.3 vs 12.8 +/- 2.7 and 10.7 +/- 1.7 vs 14.0 +/- 3.6 ng/mL at the
      end of the study for propofol and Intralipid, respectively. These results suggest
      that the antiemetic properties of propofol are not mediated via interactions with
      the dopaminergic system.

PMID- 8989025
TI  - Effects of midazolam on contractions in smooth muscle of the rabbit mesenteric
      artery.
AB  - We investigated the undetermined effects of midazolam on agonist-induced
      contraction in vascular smooth muscle strips from the rabbit mesenteric
      resistance artery. Midazolam, in concentrations more than 10 microM, attenuated
      norepinephrine ([NE] 0.3-10 microM)-induced contractions in Krebs solution. The
      attenuating effect was more potent on the tonic and oscillatory responses than on
      the rapid phasic response. When voltage-operated Ca2+ channels (VOC) were blocked
      by nifedipine, midazolam, in concentrations more than 1 microM, attenuated both
      phasic and tonic responses. In Ca(2+)-free solution, midazolam, in concentrations
      more than 1 microM, attenuated NE-induced contractions, but not caffeine-induced
      contractions. When NE and caffeine were applied successively, midazolam
      attenuated NE-induced contractions, but enhanced caffeine-induced contractions.
      Because the attenuating effect of midazolam on NE-induced contractions in high
      K+, Ca(2+)-free solution were not different from the effect in normal Ca(2+)-free
      solution, the attenuating effects of midazolam could not have been induced via
      membrane hyperpolarization. These results indicate that midazolam attenuated the
      agonist-induced contractions by inhibition of Ca2+ influx occurring not only
      through VOC, but also through agonist-mediated Ca2+ channels and by the
      inhibition of Ca2+ release from intracellular store sites.

PMID- 8989026
TI  - Hydroxyethyl starch: safe or not?

PMID- 8989027
TI  - Thoracic epidural anesthesia as the last option for treating angina in a patient
      before coronary artery bypass surgery.

PMID- 8989028
TI  - Neurologic symptoms after accidental administration of epidural glucose.

PMID- 8989029
TI  - Acute pulmonary edema in a young male after intravenous nalmefene.

PMID- 8989030
TI  - Kommerell's diverticulum: a potential cause for false diagnosis of aortic
      disruption by transesophageal echocardiography.

PMID- 8989031
TI  - Airway obstruction after ventriculoperitoneal shunt insertion in a patient with
      neurofibromatosis.

PMID- 8989032
TI  - Intraoperative hypoxia from nitrogen tanks with oxygen fittings.

PMID- 8989033
TI  - Pain on injection of rocuronium bromide.

PMID- 8989034
TI  - Dural puncture with a 26-gauge spinal needle affects spread of epidural
      anesthesia.

PMID- 8989035
TI  - Oral clonidine and postoperative pain.

PMID- 8989036
TI  - Treatment of refractory hiccups with glossopharyngeal nerve block.

PMID- 8989037
TI  - Reporting of analysis results into the operating room.

PMID- 8989038
TI  - Latex allergy to the tape of the cardio-tocograph.

PMID- 8989039
TI  - Prevention of dental trauma during endotracheal intubation.

PMID- 8989040
TI  - If nitrous oxide induces emesis, maybe 100% oxygen is an antiemetic.

PMID- 8989041
TI  - Decorative hairstyle: cause for difficult endotracheal intubation.

PMID- 8989042
TI  - Infraclavicular vertical plexus blockade: a safe alternative to the axillary
      approach?

PMID- 8989043
TI  - Intrathecal hematoma and arachnoiditis after prophylactic blood patch through a
      catheter.

PMID- 8989044
TI  - Relationship between complications of pediatric anesthesia and volume of
      pediatric anesthetics.

PMID- 8989045
TI  - Continuous intramucosal PCO2 measurement: is it actually necessary?

PMID- 8989046
TI  - Accepting the "guideline" challenge.

PMID- 8989047
TI  - Molecular biology applied to tuberculosis. The third landmark.

PMID- 8989048
TI  - Evidence-based asthma guidelines.

PMID- 8989049
TI  - Hepatic and pulmonary biopsy by mini-thoracotomy and transdiaphragmatic access.
AB  - Frequently, immunodeficient patients have more than one organ or system affected
      by opportunistic infection or neoplasia, requiring quick and precise diagnostic
      investigation. In some situations, different invasive diagnostic procedures may
      be necessary. Open lung biopsy is sometimes necessary to clarify the pulmonary
      diagnosis. Laparoscopy may be useful to clarify liver or other peritoneal
      diseases. Some specific patients might require both procedures. In this way it is
      proposed that the surgeon, through a microthoracotomy used for the pulmonary
      biopsy, has access to the diaphragm. A small phrenotomy is performed and then a
      liver needle biopsy under direct vision. The described technique of simultaneous
      open lung and hepatic biopsy permits better handling of the needle and hemostasis
      of the hepatic lesion at the puncture site. This method has been used since 1994
      on 16 HIV-positive patients, all having clinical and laboratory manifestations of
      lung disease associated with liver disease of unknown etiology. No complications
      related to the method were observed. It is significant that different etiologies
      for the lung and liver disease were found in 50% of the cases. We conclude that
      the presented technique is simple, useful, and safe.

PMID- 8989050
TI  - Thoracoscopic talc poudrage pleurodesis for malignant effusions. A review of 360
      cases.
AB  - OBJECTIVE: To assess the efficacy, permanence, and safety of thoracoscopic talc
      poudrage (TTP) for pleurodesis in malignant effusions. DESIGN: Retrospective.
      PARTICIPANTS: Patients with lifetime follow-up who received TTP in two related
      centers in Marseilles, France. RESULTS: Three hundred sixty patients were
      included in this study: 88 had mesothelioma and 272 had pleural metastases. The
      mean follow-up time was 12 months (2 to 120). Of the 327 patients whose response
      could be evaluated, 90.2% had a successful pleurodesis at 1 month, and 82.1% had
      a life-long pleural symphysis. Adverse effects included 1 death 3 days after the
      procedure in a patient with end-stage disease, fever (9.8%), empyema (2.5%),
      pulmonary infection (0.8%), and malignant invasion of the scar (1 patient).
      CONCLUSIONS: TTP is an effective and safe method of lifelong pleurodesis. It
      should be performed early on in the history of malignant effusions to avoid the
      risk of respiratory failure, this being directly linked to the general and
      respiratory status of the patients at the time of the procedure.

PMID- 8989051
TI  - Long-term outcome when major complications follow coronary artery bypass graft
      surgery. Recovery after complicated coronary artery bypass graft surgery.
AB  - OBJECTIVE: To determine whether information available 1 week after surgery
      correlates with long-term function in patients who suffer major complications
      after coronary artery bypass graft (CABG) surgery. DESIGN: An inception cohort
      study. SETTING: A 526-bed community teaching hospital. PATIENTS: All 67 patients
      who required at least 7 days of CT-ICU care following 2,751 consecutive CABG
      operations. MAIN OUTCOMES: Hospital survival, long-term survival, and functional
      ability at long-term follow-up. RESULTS: Forty-three patients survived
      hospitalization (64%), while 24 died 37 +/- 45 days (range, 7 to 190 days) after
      surgery. When 42 patients were surveyed 22 +/- 9 months after surgery, 21 of the
      survivors enjoyed excellent, independent function, 7 were moderately impaired but
      living at home, 6 were institutionalized with severe limitations, and 8 had died.
      Patients with very severe cardiac or neurologic dysfunction 1 week after surgery
      had an extremely poor outcome. When mechanical ventilation was required for
      causes other than primary failure of the respiratory system, long-term function
      and hospital survival were poor. Twelve of 14 patients with pulmonary
      complications survived hospitalization, and all 12 were alive at long-term follow
      up. CONCLUSION: More than half of patients requiring 7 days or more of ICU
      treatment after CABG surgery survive, and many enjoy excellent long-term
      function. However, those with very severe cardiac or neurologic dysfunction 1
      week after surgery have little chance for independent recovery.

PMID- 8989052
TI  - Bilateral lung volume reduction surgery for advanced emphysema. A comparison of
      median sternotomy and thoracoscopic approaches.
AB  - STUDY OBJECTIVES: To compare short-term outcomes following bilateral lung volume
      reduction surgery performed by median sternotomy (MS) and video-assisted
      thoracoscopic surgery (VATS). METHODS: Bilateral lung volume reduction surgery
      was performed by MS in 80 patients and by VATS in 40. All patients underwent
      preoperative assessment with pulmonary function testing, arterial blood gas
      determination, and 6-min walk test (6MWT). Pulmonary function testing and 6MWT
      were repeated at 3 to 6 months postoperatively. RESULTS: The mean age of the VATS
      group was lower than that of the MS group (59.3 +/- 9.4 vs 62.4 +/- 6.9 years; p
      = 0.001), but there were no differences in baseline functional parameters of
      disease severity (FEV1, FVC, residual volume [RV], arterial PCO2, or 6MWT). All
      patients in both groups were extubated at the completion of surgery, but 17.5% of
      patients in the MS group and 2.5% in the VATS group (p = 0.02) subsequently
      required reintubation at some point during the postoperative course. Thirty-day
      operative mortality was 4.2% for the MS group and 2.5% for the VATS group (p =
      not significant). However, total in-hospital mortality was 13.8% for the MS
      group, while it remained 2.5% for the VATS group (p = 0.05). Mortality was
      largely confined to patients 65 years of age or older. There was no significant
      difference in duration of air leaks or length of hospital stay between the two
      groups. Functional outcomes achieved with the two techniques were similar.
      Specifically, there was no difference between the two groups in mean
      postoperative FEV1, FVC, RV, or 6MWT, or in the magnitude of change in these
      parameters over preoperative values. CONCLUSIONS: Bilateral lung volume reduction
      surgery performed by either MS and VATS approaches leads to similar improvements
      in pulmonary function and exercise tolerance. VATS is associated with a
      significantly lower incidence of respiratory failure and a trend toward decreased
      in-hospital mortality and may be the preferred technique, particularly for high
      risk patients.

PMID- 8989054
TI  - Spirometry reference values for healthy elderly blacks. The Cardiovascular Health
      Study Research Group.
AB  - Pulmonary function was assessed by spirometry in 497 black and 2,980 white
      ambulatory elderly male and female participants of the Cardiovascular Health
      Study. The quality assurance program prompted technicians to exceed American
      Thoracic Society recommendations for spirometry. A "healthy" subgroup of 235
      black and 1,227 white participants age 65 years and older was identified by
      excluding current and former smoker, and those with self-reported asthma or
      emphysema, congestive heart failure, and poor-quality results of spirometry
      tests, since those factors were associated with a lower FEV1. Reference equations
      and normal ranges for elderly blacks for measurements of FEV1, FVC, and the
      FEV1/FVC ratio were then determined from the healthy group. These elderly blacks
      had an FVC about 6% lower than elderly whites, even after correcting for standing
      height, sitting height (trunk length), and age. The popular use of spirometry
      reference values from studies of middle-aged white subjects by applying a 12%
      race correction factor for black patients appears to overestimate predicted
      values.

PMID- 8989053
TI  - Lung function 12 months following emphysema resection.
AB  - OBJECTIVE: To investigate the mechanism of airflow limitation before and 6 and 12
      months after targeted emphysematous resection in 10 male patients aged 67 +/- 8
      years (mean +/- SD) with very severe COPD undergoing bilateral thoracoscopic
      stapling techniques. DESIGN: Lung function, including static lung elastic recoil,
      was measured 2 weeks before and 6 and 12 months after surgery. RESULTS: Twelve
      months after surgery, there was a significant (p < 0.001) reduction in total lung
      capacity (TLC), 9.5 +/- 0.3 L (mean +/- SEM) to 8.5 +/- 0.3 L, functional
      residual capacity, and residual volume. Airway conductance and FEV1, 0.71 +/- 0.1
      L (mean +/- SEM) to 0.95 +/- 0.1 L, improved significantly (p < 0.01). Lung
      elastic recoil increased markedly at TLC from 11.7 +/- 0.7 cm H2O (mean +/- SEM)
      to 15.0 +/- 1.0 cm H2O (p < 0.01) as did maximum expiratory airflow in every
      patient. However, when compared with data obtained in each patient at 6 months,
      lung volumes are significantly increased, and expiratory airflow and lung elastic
      recoil pressures are significantly reduced (p < or = 0.05). Analysis of maximum
      expiratory flow-static elastic recoil pressure curve indicates conductance of the
      S airway segment (Gs) increased from 0.20 +/- 0.03 L/s/cm H2O (mean +/- SEM) to
      0.28 +/- 0.04 L/s/cm H2O (p < 0.02), and critical transmural pressure in the
      collapsible segment (Ptm') decreased from 3.2 +/- 0.2 cm H2O (mean +/- SEM) to
      2.5 +/- 0.2 cm H2O (p < 0.01). CONCLUSION: The improvement in maximal expiratory
      airflow can be attributed primarily to increased lung elastic recoil and its
      secondary effect on enlarging airway diameter causing increased airway
      conductance, increased Gs, and decreased Ptm'. The improvement in lung function
      and elastic recoil peaks at 6 months.

PMID- 8989055
TI  - Pulmonary function in obese subjects with a normal FEV1/FVC ratio.
AB  - STUDY OBJECTIVE: To determine pulmonary function test (PFT) profile and
      respiratory muscle strength (RMS) of a group of obese individuals who did not
      have evidence of obstructive airway disease or other underlying diseases
      affecting their respiratory system. DESIGN: Prospective, open. SETTING: PFT
      laboratory, VA Medical Center. PARTICIPANTS: Sixty-three consecutive obese (body
      mass index greater than 27.8 kg/m2) male subjects without overt obstructive
      airway disease (FEV1/FVC ratio greater than 80%). MEASUREMENTS AND RESULTS:
      Standard PFTs and maximum static inspiratory (PImax) and expiratory (PEmax) mouth
      pressures were determined. RMS was calculated from the following formula:
      (PImax+PEmax):2. Two distinct groups were identified, those with normal maximum
      voluntary ventilation (MVV) (> 80% predicted) and those with low MVV. Both
      inspiratory and expiratory flow rates (FVC, FEV1, forced expiratory flow at 50%
      vital capacity [V50], maximum inspiratory flow rate [MIFR]), lung volumes (vital
      capacity [VC], inspiratory capacity [IC], expiratory reserve volume), PImax, and
      RMS were significantly lower, and residual volume/total lung capacity (RV/TLC)
      ratio was significantly higher in obese subjects with low MVV compared with those
      in whom MVV was normal. MVV correlated significantly with FVC, FEV1, V50, MIFR,
      TLC, VC, IC, RV/TLC, and RMS; the strongest correlation was with MIFR (r = 0.76,
      p < 0.0001). CONCLUSIONS: Standard PFTs allow recognition of a subgroup of obese
      subjects without overt obstructive airway disease who have more severe lung
      dysfunction, the marker of which is a low MVV. Peripheral airway abnormalities
      may be responsible for these observations.

PMID- 8989056
TI  - Membrane diffusion and capillary blood volume in chronic thromboembolic pulmonary
      hypertension.
AB  - A reduced diffusing capacity for carbon monoxide (DCO) is common among patients
      with chronic thromboembolic pulmonary hypertension (CTEPH) and often persists for
      more than a year following successful pulmonary thromboendarterectomy (PTE). To
      determine the relative contribution the pulmonary membrane diffusing capacity
      (DM) and pulmonary capillary blood volume (VC) make to the reduction in DCO, we
      measured both in 29 patients with CTEPH before and approximately 3 weeks after
      PTE. Mean preoperative DM was reduced in patients with CTEPH (28 mL min-1 mm Hg-1
      vs 43 mL min-1 mm Hg-1 in control subjects; p < 0.001) and dropped significantly
      following PTE (21 mL min-1 mm Hg-1; p < 0.001). Mean preoperative VC was mildly
      reduced in the CTEPH group compared with healthy control subjects (57 vs 67 mL; p
      = 0.044) and did not rise following PTE (57 mL pre-PTE vs 54 mL post-PTE; p >
      0.05) despite substantial reduction in mean pulmonary artery pressure and
      increase in cardiac output after surgery. We conclude that the low DCO observed
      in patients with CTEPH before and after PTE is principally caused by a reduced DM
      and to a lesser extent by a low VC. The mechanisms responsible remain speculative
      but may reflect pathophysiologic changes in the pulmonary microcirculation caused
      by chronic pulmonary hypertension that did not improve in the postoperative
      period studied.

PMID- 8989057
TI  - Theophylline improves measurements of respiratory muscle efficiency.
AB  - To determine the effect of theophylline on respiratory muscle efficiency (RME),
      12 normal subjects were given theophylline vs placebo in a double-blind,
      randomized crossover protocol. Spirometry, resting energy expenditure, minute
      ventilation, RME and oxygen cost of breathing were measured at baseline, after
      taking theophylline, and after placebo. RME was calculated by dividing the added
      work required to breathe through a threshold load by the added energy consumed
      during loaded breathing. Oxygen cost of breathing was calculated by dividing the
      increase in oxygen consumption induced by breathing an air/carbon dioxide mixture
      by the associated increase in minute ventilation. RME increased from 3.3 +/- 1.6%
      at baseline to 7.9 +/- 3.2% after theophylline (p < 0.01) but did not change
      significantly after placebo (4.8 +/- 2.4%). Oxygen cost of breathing decreased
      from 3.9 +/- 2.4 mL O2 per liter at baseline to 1.7 +/- 0.7 mL O2 per liter after
      theophylline (p < 0.05) but did not change significantly after placebo (2.8 +/-
      1.3 mL O2 per liter). Theophylline use was also associated with an 18% increase
      in minute ventilation (p < 0.01) and a 15.7% increase in resting energy
      expenditure (p < 0.01). Theophylline improves measured RME and reduces oxygen
      cost of breathing in normal subjects. These effects are offset by increases in
      resting energy expenditure and minute ventilation.

PMID- 8989059
TI  - The association between asthma drugs and severe life-threatening attacks.
AB  - OBJECTIVES: To measure the association between asthma drugs and death or ICU
      admission due to asthma (severe life-threatening attack of asthma [SLTA]), and to
      assess the possibility that these associations may not be causal but due to the
      prescription of these drugs to patients with more severe disease (confounding).
      DESIGN: Retrospective cohort study of 655 asthmatics who attended an emergency
      department in 1986 to 1987 followed till death or May 1989. METHODS: Outcome
      events were death or ICU admission due to asthma (SLTA). All hospital attendances
      were identified and patients classified at each according to drug exposure and a
      wide variety of measures of asthma severity. Incidence rates were computed as
      total outcome events divided by person-time contributed for each subject
      classified according to drug use and asthma severity. Rate ratio (RR) estimates
      for severe asthma outcomes associated with use as compared to nonuse of asthma
      drugs were calculated. Severity markers were identified and used to adjust the
      crude RR estimates. RESULTS: One hundred five SLTAs (15 deaths, 90 ICU
      admissions) occurred in 66 patients. Like inhaled fenoterol, oral beta-agonists,
      theophylline, cromolyn, inhaled steroids, and oral steroids were all associated
      with an increased risk of SLTA. When adjusted progressively for measures of
      severity, these increased risks became insignificant except for cromolyn.
      CONCLUSION: Unadjusted RR estimates for severe asthma events comparing exposure
      to a particular drug with nonuse are overestimates due to confounding. Control
      with two severity markers (hospital admission in the last year, use of oral
      corticosteroid at the time of previous admission) removes some confounding but
      control for additional severity markers not available in previous studies reduces
      the effect estimates further. These results suggest that the problem of
      confounding is substantial in nonrandomized epidemiologic studies of asthma
      drugs. Previous studies reporting RR estimates are likely to be confounded.

PMID- 8989058
TI  - Pain during arterial puncture.
AB  - STUDY OBJECTIVE: To quantify the level of pain reported by patients during
      arterial puncture with or without local anesthesia, and to compare the results
      with levels reported for venous puncture. DESIGN: Double-blind study of puncture
      with and without local anesthesia. SETTING: Pulmonary function laboratory,
      department of pneumology. PATIENTS: We studied 270 consecutive patients
      undergoing arterial puncture divided into two groups. In group A (n = 210), we
      assessed level of pain with and without local anesthesia and with placebo. In
      group B (n = 60), we compared pain of arterial and venous puncture.
      INTERVENTIONS: The arterial puncture was performed in the radial artery; venous
      puncture was in the median basilic vein. MEASUREMENTS AND RESULTS: The pain was
      quantified on a visual analog scale (10 cm). Mean level of pain for all arterial
      punctures without anesthesia or placebo was slight to moderate (3.01 +/- 1.94
      cm). Subcutaneous anesthetic infiltration before arterial puncture significantly
      reduced pain by more than 50%, to 1.50 +/- 1.54 cm, a level that was
      significantly lower than the pain level reported after conventional venous
      puncture (1.80 +/- 1.10 cm). The pain reported by patients who received no
      anesthesia was not significantly different (p = 0.45) from that perceived by
      those who received subcutaneous infiltration of saline solution (placebo).
      CONCLUSIONS: Arterial puncture with prior infiltration of local anesthetic is the
      least painful procedure among those studied. Use of local anesthesia is indicated
      whenever conventional arterial puncture is required.

PMID- 8989060
TI  - Tolerance to the protective effect of salmeterol on allergen challenge.
AB  - Long-term treatment with inhaled beta 2-agonists may be associated with a
      deterioration in asthma control, potentially due to tolerance. Regular use of
      short-acting beta 2-agonists has been shown to induce tolerance to allergen or
      adenosine 5'-monophosphate challenge. The aim of the study was to detect the
      efficacy of a single dose and a short-term treatment with salmeterol, a long
      acting beta 2-agonist, to protect against early asthmatic reaction (EAR) to
      allergen. Eight subjects with mild allergic asthma underwent two treatment
      periods in which subjects performed an allergen challenge (specific bronchial
      provocation test) protected by a single dose (50 micrograms) of salmeterol (Salm
      1) followed by a second specific bronchial provocation test after regular
      treatment with salmeterol for 1 week (Salm-2), or a single dose of placebo (Plac
      1) and regular treatment (1 week) with placebo (Plac-2). Each subject performed
      both treatments in a randomized order. Each time allergen challenge was performed
      1 h after last drug inhalation and it was stopped when the same provocative dose
      of allergen of a previous screening allergen challenge was achieved. The maximum
      decrease in FEV1 and area under curve in the first hour after allergen inhalation
      were significantly lower in Salm-1 (max delta FEV1 %, median [range]: 4%[0 to 9])
      with respect to Salm-2, Plac-1, Plac-2 (24%[13 to 38], 31%[19 to 50], 30%[6 to
      44], respectively, p < 0.001); there was no difference among Salm-2, Plac-1 and
      Plac-2. In Salm-1, all subjects were protected against EAR, whereas in Salm-2
      only 2 subjects showed a partial protection. In conclusion the protective effect
      of a single dose of salmeterol against allergen-induced EAR was lost after
      regular treatment with salmeterol for 1 week. The clinical relevance of this
      mechanism remains to be elucidated.

PMID- 8989061
TI  - Periodicity of asthma, emphysema, and chronic bronchitis in a northwest health
      maintenance organization.
AB  - STUDY OBJECTIVE: Since seasonal patterns in morbidity may identify triggers
      provoking hospital-based care for airflow obstruction, this study examined
      seasonal variation in patterns of hospitalizations for asthma, chronic
      bronchitis, and emphysema. DESIGN AND SETTING: The data for this analysis were
      derived from the abstracted medical records of a large health maintenance
      organization, Kaiser Permanente, Northwest region, over the period 1979 to 1987.
      PATIENTS: In all, 2,060 primary hospital discharges for asthma and 1,121 primary
      hospital discharges for the combination chronic bronchitis/emphysema were
      observed. RESULTS: The monthly patterns varied for asthma and chronic
      bronchitis/emphysema, and also varied by age and sex. For young children 0 to 14
      years, asthma hospitalizations peaked primarily in the fall. In contrast, for
      young children 0 to 14 years, hospitalizations for chronic bronchitis/ emphysema
      peaked in the fall/winter months. Seasonal variation decreased as age increased
      for chronic bronchitis/emphysema, such that for the 65+ year group, there was no
      seasonal variation. CONCLUSION: A better understanding of the causes of the age
      specific seasonal patterns in these obstructive respiratory diseases may help to
      reduce the morbidity that is associated with them.

PMID- 8989062
TI  - Differential influences on asthma self-management knowledge and self-management
      behavior in acute severe asthma.
AB  - AIM: While asthma education increases knowledge, it is less clear whether
      education influences actual patient behavior. To determine whether there are
      differences between asthma self-management knowledge and the actual behavior of
      patients during an acute severe asthma attack and to determine which clinical and
      psychosocial factors are associated with knowledge and behavior. METHODS:
      Validated hypothetical scenarios describing the development of life-threatening
      asthma and patients' reported actual behavior were scored (out of 25) using a
      system based on Thoracic Society of Australia and New Zealand and British
      Thoracic Society criteria. RESULTS: In 137 patients admitted to the hospital with
      severe asthma, the pattern of the index attack was slow onset (> or = 6 h) in
      96%. The score for the hypothetical attack (knowledge) was 13.8 +/- 4.6, while
      that for the timeline (behavior) was 10.2 +/- 3.9 (p < 0.001) with 56% and 84%,
      respectively, having a score of less than 15 (regarded as inadequate). Certain
      components showed marked discrepancy (eg, appropriately seeking medical help 82%
      vs 52% (p < 0.001) and calling ambulance 61% vs 23% (p < 0.001). Factors such as
      physician-patient relationship, previous asthma morbidity, availability of peak
      flowmeter, action plan, and oral steroids correlated positively with both
      measures. Knowledge was negatively associated with being non-European, with
      anxiety, pessimism, and stigmatization. Behavior (but not knowledge) was
      negatively associated with lack of knowledge of what to do in the index attack,
      previous emotional counseling, and business failure. Those factors associated
      with the difference between knowledge and behavior scores (knowledge-behavior
      gap) were being non-European, anxiety, pessimism, and stigmatization, concerns
      about medical costs, and the only income for the household being a Social
      Security benefit. CONCLUSION: There are marked differences between patients' self
      management knowledge and their actual behavior, particularly in terms of
      potentially life-saving actions. Psychological, health-care, and socioeconomic
      factors have a powerful and differential influence on knowledge and behavior.
      Improved understanding of the discrepancies between knowledge and behavior and
      which factors influence them may lead to more effective asthma educational
      interventions.

PMID- 8989063
TI  - Type of lymph node involvement influences survival rates in T1N1M0 non-small cell
      lung carcinoma. Lymph node involvement by direct extension compared with lobar
      and hilar node metastases.
AB  - Stage II non-small cell lung cancer represents a group of patients with varying 5
      year survival rates. Of 2,009 patients, we reviewed 58 patients with pT1N1M0
      disease operated on from 1977 through 1994. The N1 status was refined into lymph
      node involvement by direct extension and/or involvement by metastases (lobar or
      hilar). The cumulative 5-year survival of all hospital survivors (n = 57) was
      45.7%. The 5-year survival of patients with N1 direct extension was superior to
      survival of patients with N1 metastases (68.6% vs 31.2%; p = 0.0038). Survival of
      patients with N1 direct extension was better then survival of patients with N1
      hilar metastases (p = 0.0006), but did not differ from survival of patients with
      lobar metastases. Survival was not related to histologic features, sex, and type
      of resection. Recurrence of malignancy occurred less in patients with N1 direct
      extension. In patients with N1 hilar nodes, the most common pattern was distant
      metastases. Survival differs according to the type of lymph node involvement:
      "direct extension" seems to be an early stage of the disease, while lymph node
      metastases represent a more advanced form.

PMID- 8989064
TI  - The changing radiographic presentation of bronchogenic carcinoma with reference
      to cell types.
AB  - OBJECTIVE: To analyze chest radiographic patterns of lung cancer at presentation
      by cell type. This current series is compared with historic published data.
      DESIGN: Retrospective, using a tumor registry. SETTING: Large, rural
      multispecialty clinic. PATIENTS: Three hundred forty-five patients with newly
      diagnosed lung cancers presenting between October 1990 and August 1992. METHODS:
      Radiographs were interpreted by two radiologists blinded to cell type. Our
      results were compared statistically to published data from Mayo Clinic patients
      in the 1950s and 1960s. RESULTS: (1) Adenocarcinoma: Decreased presentation as a
      peripheral tumor in current series (49%) compared with historic control at Mayo
      (72%); (2) squamous cell: increased presentation as peripheral tumor in current
      series (43%) compared with historic control (31%); and (3) no statistically
      significant difference between adenocarcinoma (49%) and squamous (43%) for a
      presentation as a peripheral mass, or between adenocarcinoma (46%) and squamous
      (52%) for central origin in the current series of cases. CONCLUSION: As
      adenocarcinoma has increased in relative frequency among lung cancers, the
      percent of cases with peripheral primary tumors is decreased while central tumors
      have increased. Squamous carcinoma has had a relative increase in peripheral mass
      presentation. There is now no significant difference between these two cell types
      in percent presenting as a peripheral mass or central tumor on chest radiograph.

PMID- 8989065
TI  - Pulmonary artery sarcoma. Clinical features.
AB  - STUDY OBJECTIVES: To define characteristic clinical and radiographic
      presentations of patients found to have primary sarcoma of the pulmonary artery
      and differentiate this entity from acute and chronic pulmonary thromboembolism.
      To review pathologic characteristics of pulmonary artery sarcoma. DESIGN: A
      retrospective review of medical records at a large medical center and a review of
      the literature. SETTING: Tertiary care medical center. PATIENTS: Patients found
      to have pulmonary artery sarcoma based on surgical or autopsy findings.
      INTERVENTIONS: Review of medical records. MEASUREMENTS AND RESULTS: Presenting
      symptoms of patients with pulmonary artery sarcoma are similar to those of
      patients with other pulmonary vascular disease, including progressive dyspnea,
      cough, hemoptysis, and chest pain. Symptoms not commonly associated with
      pulmonary vascular disease consist of progressive weight loss, anemia, and fever,
      which are symptoms commonly associated with malignancy. The diagnosis is often
      not suspected prior to surgery, which is often undertaken with an alternative
      diagnosis such as bronchogenic carcinoma or chronic pulmonary thromboembolism.
      Prolonged survival is rare; most patients survive only a few months. Survival
      longer than 3.5 years was not observed. Recent experience with MRI of the thorax
      and transesophageal echocardiography suggests that these diagnostic entities may
      be rewarding in separating the abnormalities seen on chest radiographs and
      angiography from thrombus in the pulmonary artery, mediastinal adenopathy, or
      primary bronchogenic carcinoma. CONCLUSIONS: Although a rare entity, the key is
      to suspect the presence of pulmonary artery sarcoma in evaluation of patients
      with atypical presentations of pulmonary vascular disease especially if
      associated with symptoms such as weight loss, fever, or anemia.

PMID- 8989066
TI  - Normal oxyhemoglobin saturation during sleep. How low does it go?
AB  - STUDY OBJECTIVE: To determine oxyhemoglobin saturation (O2 Sat) in healthy
      humans. DESIGN: Retrospective review of all-night pulse oximetry data, carefully
      examined to exclude periods of motion artifact. The lowest saturation recorded
      during the night (Low Sat), the median saturation (Sat 50), and the saturation
      below which the patient spent 10% of the time (Sat 10) were tabulated. These data
      were compared to the O2 Sat in patients with obstructive sleep apnea (OSA) and
      patients with stable asthma. SETTING: Sleep laboratory in a tertiary care
      hospital. PATIENTS: Three hundred fifty people with normal results of overnight
      polysomnography. Patients with known craniofacial or neurologic abnormalities or
      any previously diagnosed pulmonary disease such as asthma or COPD were excluded.
      The healthy subjects ranged in age from 1 month to 85 years. There were 184 male
      and 166 female subjects. These were compared to 25 patients with OSA and 21
      patients with asthma. RESULTS: For the healthy patients, the mean +/- SD Low Sat
      was 90.4% +/- 3.1%. The mean Sat 10 was 94.7% +/- 1.6%. The mean Sat 50 was 96.5%
      +/- 1.5%. There was no relationship between any of the O2 Sat measures and sex,
      race, or obesity as measured by body mass index. However, older subjects (> 60
      years of age) had lower Sat 10 (92.8 +/- 2.3) and Sat 50 (95.1 +/- 2.0) than did
      younger subjects. The O2 Sat of the patients with asthma was not different from
      the healthy subjects, but the patients with OSA had a significantly lower Sat 50,
      Sat 10, and Low Sat. SUMMARY: We describe in detail O2 Sat in a large group of
      healthy people. Older subjects without known cardiorespiratory disease have lower
      O2 Sat than younger subjects.

PMID- 8989067
TI  - Posture-dependent change of tracheal sounds at standardized flows in patients
      with obstructive sleep apnea.
AB  - BACKGROUND: The ability of awake subjects with obstructive sleep apnea (OSA) to
      dilate their pharynx during inspiration may be defective. Airflow through a
      relatively more narrow pharyngeal passage should lead to increased flow
      turbulence and hence to louder respiratory sounds. We therefore studied the
      increase of tracheal sound intensity (TSI) in the supine position as an indicator
      of abnormal pharyngeal dynamics in patients with documented OSA. SUBJECTS AND
      METHODS: Sound was recorded with a contact sensor at the suprasternal notch in 7
      patients with OSA (age, 52 +/- 8 years; body mass index, 29.0 +/- 3; apnea
      hypopnea index, 58 +/- 17; means +/- SD), and in 8 control subjects, including
      obese subjects and snorers (age, 39 +/- 8 years; body mass index, 28.6 +/- 4).
      Subjects breathed through a pneumotachograph and aimed at target flows of 1.5 to
      2 L/s, first sitting, then supine. Flow and sound signals were digitized at a 10
      KHz rate. Fourier analysis was applied to sounds within the target flow range and
      average power spectra were obtained. Spectral power was calculated for frequency
      bands 0.2 to 1, 1 to 2, and 2 to 3 KHz. RESULTS: In the supine position, OSA
      patients had a significantly greater increase of inspiratory TSI than control
      subjects: 7.5 +/- 1.2 dB vs 1.7 +/- 3.4 dB (p < 0.001); 6.6 +/- 1.7 dB vs 1.3 +/-
      3.9 dB (p < 0.005); and 12.2 +/- 3.2 dB vs 5.6 +/- 3.1 dB (p < 0.001) at low,
      medium, and high frequencies, respectively. Expiratory TSI also increased in
      supine subjects, but the change was significantly greater in OSA subjects only at
      high frequencies. These findings confirm our earlier observations that did not
      include obese subjects or snorers among control subjects. SUMMARY: Measuring
      posture effects on tracheal sounds is noninvasive and requires little time and
      effort. The greater increase of inspiratory TSI in supine OSA patients compared
      to subjects without OSA suggests a potential value for daytime acoustic
      screening.

PMID- 8989068
TI  - Oral empiric treatment of community-acquired pneumonia. A multicenter, double
      blind, randomized study comparing sparfloxacin with roxithromycin. The
      Scandinavian Sparfloxacin Study Group.
AB  - STUDY OBJECTIVE: Comparison of efficacy and safety of sparfloxacin (Spfx) vs
      roxithromycin (ROXI) for treatment of community-acquired pneumonia (CAP). DESIGN:
      Multicenter, double-blind, randomized study. SETTING: Twenty-three university and
      community hospitals in Scandinavia. PATIENTS: Three hundred four adults (> or =
      18 years of age) with CAP treated as outpatients (25%) or inpatients (75%).
      INTERVENTIONS: Randomization 1:1 to Spfx, 400 mg on day 1, then 200 mg once
      daily, or ROXI, 150 mg twice daily, 10 to 14 days. Safety and efficacy analyses
      in intention-to-treat (ITT) and evaluable populations. RESULTS: Three hundred
      three of 304 patients were included in the ITT and safety analyses and 260 (86%)
      were evaluable at the end of follow-up. Streptococcus pneumoniae was the cause of
      pneumonia in 62 (20%) patients (11 with bacteremia), Chlamydia pneumoniae in 40
      (13%), and Mycoplasma pneumoniae in 38 (13%) patients. The success rates for Spfx
      and ROXI at the end of follow-up were 82% and 72%, respectively, in the ITT
      population, and 94% and 79%, respectively, in the evaluable population. The odds
      ratio Spfx/ROXI for success was 4.5 (95% confidence interval, 1.9, 10.8) for the
      evaluable population. Both drugs were, overall, equally safe. GI symptoms were
      the most common adverse experiences in both groups. Prolongation of QTc, without
      clinical symptoms, was seen in 3% of Spfx patients and in 1% of ROXI patients,
      and photosensitivity, mostly mild to moderate, was seen in 5% of the Spfx group.
      CONCLUSIONS: Oral treatment with Spfx was superior to ROXI for the treatment of
      moderately severe CAP. Spfx was effective for all isolated pathogens, including S
      pneumoniae, and may be an alternative for empiric treatment of CAP, especially in
      areas with a high incidence of beta-lactam-resistant pneumococci.

PMID- 8989069
TI  - Fluconazole vs itraconazole-flucytosine association in the treatment of
      esophageal candidiasis in AIDS patients. A double-blind, multicenter placebo
      controlled study. The Candida Esophagitis Multicenter Italian Study (CEMIS)
      Group.
AB  - STUDY OBJECTIVE: To assess the role and the therapeutic efficacy of fluconazole
      and itraconazole-flucytosine association compared with placebo, in the treatment
      of endoscopically diagnosed esophageal candidiasis in a selected population of
      AIDS patients. DESIGN: Double-blind, placebo-controlled study. SETTING:
      University Hospitals and AIDS Centers. PATIENTS: Eighty-five HIV-positive
      patients (53 men and 32 women; mean age, 28 years) at first episode of esophageal
      candidiasis diagnosed by endoscopy (grades I to II of Kodsi's endoscopic
      classification and grades I to IIa of Barbaro's clinical classification). All the
      patients selected for the study provided informed consent. INTERVENTIONS: The
      patients have been double blindly randomized in 3 groups of patients in relation
      to pharmacologic therapy: (1) the patients of the first group (n = 30) received
      fluconazole (3 mg/kg daily orally) and placebo (100 mg/kg/daily orally); (2) the
      patients of the second group (n = 30) received itraconazole (3 mg/kg daily
      orally) and flucytosine (100 mg/kg daily orally); and (3) the patients of the
      third group (n = 25) received placebo (3 mg/kg daily orally) and placebo (100
      mg/kg daily orally). After 2 weeks of treatment, the patients previously
      randomized to receive placebo only were double blindly randomized to receive
      fluconazole+placebo or itraconazole+flucytosine. To evaluate the efficacy of
      pharmacologic therapy, clinical and endoscopic examinations were performed at
      weeks 2 and 4 and at the end of follow-up (3 months). RESULTS: At week 2,
      endoscopic cure (grade 0) was observed in 68.9% of the fluconazole+placebo group
      and in 72.4% of the itraconazole+flucytosine group (relative risk, 0.95; 95%
      confidence interval [CI], 0.68 to 1.33; p = 0.772); partial endoscopic response
      (grade I) was observed in 22.7% of the placebo group. Clinical cure (grade 0) was
      observed in 75.8% of fluconazole+placebo group and in 72.4% of
      itraconazole+flucytosine group (relative risk, 1.05; 95% CI, 0.77 to 1.42; p =
      0.764), with a difference statistically significant for both treatments in
      comparison to placebo group (p < 0.001). Partial clinical response (grade I) was
      observed in 27.3% of the placebo group. At the end of follow-up, endoscopic cure
      was observed in 89.8% of the fluconazole+placebo group and in 94.8% of the
      itraconazole+flucytosine group (relative risk, 0.97; 95% CI, 0.83 to 1.08; p =
      0.695). Clinical cure was observed in 94.8% of the fluconazole+placebo group and
      in 97.3% of the itraconazole+flucytosine group (relative risk, 0.97; 95% CI, 0.89
      to 1.07; p = 0.981). CONCLUSIONS: The results of this study have demonstrated
      that both fluconazole and itraconazole+flucytosine association are efficacious in
      short-term treatment of esophageal candidiasis in AIDS patients with a
      statistically significant difference in comparison to placebo. Both therapeutic
      regimens demonstrated a good therapeutic efficacy, without statistically
      significant difference, between them, in the rate of endoscopic and clinical
      cure. Itraconazole+flucytosine association may represent an alternative
      therapeutic regimen for patients with fluconazole-resistant Candida esophagitis.

PMID- 8989070
TI  - Prevalence of pulmonary hypertension in limited and diffuse scleroderma.
AB  - STUDY OBJECTIVES: To characterize the prevalence of undiagnosed pulmonary
      hypertension in patients with limited and diffuse scleroderma. DESIGN:
      Prospective cross-sectional study. SETTING: University-based outpatient clinic.
      PATIENTS: Thirty-four consecutive patients with limited (n = 29) or diffuse (n =
      5) scleroderma but without the clinical diagnosis of pulmonary hypertension.
      MEASUREMENTS AND RESULTS: All patients had 12-lead ECGs and two-dimensional and
      Doppler echocardiograms. The pulmonary artery systolic pressure (PAs) was
      calculated as the sum of the Doppler transtricuspid pressure gradient and the
      right atrial pressure as estimated by the caval respiratory index. Thirty-three
      patients (97%) had adequate spectral signals of tricuspid regurgitation. The
      velocity of tricuspid regurgitation ranged from 1.6 to 4.5 m/s. The calculated
      PAs ranged from 15 to 95 (mean +/- SD = 30 +/- 14 mm Hg). Twelve patients (35% of
      the total cohort) had pulmonary hypertension defined as PAs of 30 mm Hg or
      greater. CONCLUSIONS: Undiagnosed elevation of PAs is common in patients with
      scleroderma. Noninvasive assessment of PAs can be performed accurately in most
      patients independent of clinical signs of pulmonary hypertension. If successful
      treatment strategies are identified, it may be possible to identify patients
      early in the development of pulmonary hypertension and intervene before
      significant end-organ damage occurs.

PMID- 8989071
TI  - Cardiorespiratory responses to incremental exercise in patients with systemic
      sclerosis.
AB  - Patients with systemic sclerosis are known to have histologic pulmonary
      abnormalities despite normal chest radiograph or conventional pulmonary function
      or both. In an attempt to detect early features of lung involvement in
      progressive systemic sclerosis, we investigated patients with systemic sclerosis
      using cardiopulmonary exercise testing. We have studied 78 patients who fulfilled
      the American Rheumatism Association criteria for the classification of systemic
      sclerosis, and according to the classification of LeRoy, 44 had limited cutaneous
      systemic sclerosis and 34 had diffuse cutaneous systemic sclerosis. A
      significantly decreased diffusing capacity (65 +/- 3% of that predicted) was
      present only in the group with diffuse cutaneous systemic sclerosis. The patients
      with lung involvement showed a significant reduction in exercise capacity (54 +/-
      3% of that predicted) and in oxygen uptake (70 +/- 3% of that predicted).
      Additionally, we could demonstrate an increased functional dead space ventilation
      (0.34 +/- 0.02) and widened alveolar-arterial oxygen difference during exercise
      (44 +/- 3 mm Hg). By cardiopulmonary exercise testing, 12 of the 78 patients
      (15%) with normal single-breath diffusing capacity for carbon monoxide had
      increased dead space to tidal volume ratio. Our results suggest that occult
      pulmonary impairment may be present in patients with normal pulmonary function
      and that cardiopulmonary exercise testing enables detection of such impairment.
      Our study results show the limitations of resting data in predicting
      abnormalities during exercise in patients with systemic sclerosis.

PMID- 8989072
TI  - Exercise training decreases dyspnea and the distress and anxiety associated with
      it. Monitoring alone may be as effective as coaching.
AB  - STUDY OBJECTIVE: To determine whether exercise training with coaching is more
      effective than exercise training alone in reducing dyspnea and the anxiety and
      distress associated with it and improving exercise performance, self-efficacy for
      walking, and dyspnea with activities of daily living. DESIGN: Randomized clinical
      trial of 51 dyspnea-limited patients with COPD assigned to monitored (n = 27) or
      coached (n = 24) exercise groups. SETTING: Outpatient area of university teaching
      hospital. INTERVENTION: Both groups completed 12 supervised treadmill training
      sessions (phase 1) over 4 weeks followed by 8 weeks of home walking (phase 2).
      The CE group also received coaching during training. MEASUREMENTS: Perceived work
      of breathing, dyspnea intensity, distress associated with dyspnea, and anxiety
      associated with dyspnea were rated on a visual analog scale during incremental
      treadmill testing and after 6-min walks before and after phase 1. Dyspnea with
      activities of daily living, self-efficacy for walking, state anxiety, and 6-min
      walks were measured before and after both phases. RESULTS: Dyspnea and the
      associated distress and anxiety improved significantly for both groups relative
      to work performed and in relation to ventilation (p < 0.05). There were no
      significant differences between groups in any outcomes. The phase 1 improvement
      in laboratory dyspnea was accompanied by improvements in dyspnea with activities
      of daily living (p < 0.01) and self-efficacy for home walking (p < 0.01) that
      were sustained during the home phase. CONCLUSIONS: Coaching with exercise
      training was no more effective than exercise training alone in improving exercise
      performance, dyspnea, and the anxiety and distress associated with it, dyspnea
      with activities, and self-efficacy for walking.

PMID- 8989073
TI  - Endoscopic treatment of malignant airway obstructions in 2,008 patients.
AB  - We report our 13-year experience with endoscopic treatment of malignant
      obstructions of the airway by Nd:YAG laser, stents, and intraluminal
      brachytherapy in 2,008 patients. We performed 2,610 laser resections in 1,838
      patients, 66 high dose rate brachytherapies, and we placed 393 tracheobronchial
      silicone stents in 306 patients. We used the rigid bronchoscope in 96% of the
      laser procedures and in all cases requiring stent placement; general anesthesia
      was given to 90% of these patients. Endobronchial radiotherapy was performed
      under local, anesthesia. In 93% of patients undergoing laser resection, we
      obtained an immediate patency of the airway with consequent improvement of
      quality of life. The median time between the first and second laser treatment was
      102 days, being longer in the case of stent placement (when required) or in
      association with brachytherapy. Even if endoscopic treatment should be considered
      only for palliation, laser vaporization could be curative in case of in situ
      carcinoma. Since 1983, we have treated 23 such lesions in 17 patients and up to
      now, none has recurred. Finally, endoscopic resection may allow a better
      assessment of the true extent of the tumor, shifting to surgery patients
      originally considered to have inoperable disease or allowing lung-sparing
      operations (21 and 18 patients of our series, respectively). The total mortality
      rate was 0.4% (12 patients over 2,798 treatments; 2,710 Nd:YAG laser + 151 stents
      without laser + 37 brachytherapies without laser) in the first week after the
      procedures, and was mainly related to cardiovascular problems and respiratory
      failure. In conclusion, endoscopic resection of lung malignancies is rapid,
      effective, repeatable, and complementary to other treatments; although it should
      be considered only palliative, laser resection could be curative in patients with
      in situ carcinomas and early cancers. Laser, stents, and endoluminal
      brachytherapy should be available in all centers with major experience; a well
      trained team is mandatory to plan the most appropriate treatment and manage any
      possible complication.

PMID- 8989074
TI  - Development of an ultrathin fiberscope with a built-in channel for bronchoscopy
      in infants.
AB  - Flexible fiberoptic bronchoscopy (FFB) is of great importance for diagnostic and
      therapeutic purposes in pediatric respiratory management. However, lack of a
      built-in channel in commercially available ultrathin fiberscopes has limited its
      usefulness in neonates and infants. Bronchoscopic procedures, including
      suctioning, BAL, bronchography, and selective drug injection have instead been
      performed by temporary extubation followed by mask ventilation. However, such
      techniques are not suitable for repeated FFB and are open to considerable risks,
      especially in critically ill patients. In this context, we developed a directable
      ultrathin fiberscope with an external diameter of 2.7 mm and a 0.8-mm internal
      diameter built-in channel. This prototype fiberscope, the XPF27, is useful during
      spontaneous ventilation and can be inserted through a 3.5-mm or larger
      endotracheal tube. The XPF27 was utilized for 55 FFB procedures and allowed
      suctioning, BAL, bronchial toileting, and bronchography in 16 critically ill
      children without complications. We conclude that XPF27 is useful for pediatric
      FFB despite its limited flexibility, visual field, and resolution.

PMID- 8989075
TI  - Validation of an inexpensive B-mode ultrasound device for detection of deep vein
      thrombosis.
AB  - OBJECTIVE: To validate a portable, inexpensive, real-time, B-mode ultrasound
      device compared with duplex ultrasound in the detection of proximal lower
      extremity deep vein thrombosis in hospitalized patients clinically suspected of
      having deep vein thrombosis. DESIGN: Prospective cohort study. SETTING: Tertiary
      care community teaching hospital. PATIENTS: Medical-surgical hospitalized
      patients undergoing duplex ultrasonography for clinically suspected lower
      extremity deep vein thrombosis. INTERVENTIONS: Hospitalized patients who
      underwent duplex ultrasound examinations were enrolled in the study. Blinded from
      the duplex ultrasound results, the investigators utilized the study ultrasound
      device to perform compression ultrasonography of the common femoral, superficial
      femoral, and popliteal veins within 48 h of the duplex examinations. The results
      of the study ultrasound device were recorded as normal (compressible) or abnormal
      (noncompressible). RESULTS: Of the 198 lower limbs evaluated, duplex
      ultrasonography documented 34 proximal lower extremity deep vein thrombi. The
      study ultrasound device detected 32 of the 34 proximal thrombi detected by duplex
      ultrasonography. One false-positive result of an examination occurred with the
      study ultrasound device. Compared with duplex ultrasonography, the study
      ultrasound device had a sensitivity of 94%, specificity of 99%, positive
      predictive value of 97%, and negative predictive value of 98%. CONCLUSIONS: The
      results of this investigation document that the study ultrasound device has an
      acceptable sensitivity, specificity, and diagnostic accuracy for clinical use in
      detection of proximal lower extremity deep vein thrombosis. Further evaluation
      and validation of this ultrasound device are warranted.

PMID- 8989076
TI  - Assessment of the motor pathway to the diaphragm using cortical and cervical
      magnetic stimulation in the decision-making process of phrenic pacing.
AB  - BACKGROUND: Phrenic nerve pacing is a recognized substitute to positive pressure
      ventilation via tracheotomy in patients with high cervical cord lesions or
      central hypoventilation. Although its indications are infrequent, reliable
      strategies need to be used in the determinations of patients who may benefit from
      this treatment; contraindications should be carefully respected. STUDY
      OBJECTIVES: To determine whether modern and noninvasive means to study the motor
      pathway to the diaphragm, namely cortical magnetic stimulation (CxMS) and
      cervical magnetic stimulation (CMS), can contribute to the selection of patients
      who may benefit from phrenic pacing. DESIGN AND SETTING: Prospective study (18
      months), on a consecutive basis, of patients referred for possible phrenic pacing
      to a 10-bed ICU associated with a respiratory neurophysiology laboratory.
      PATIENTS: Seven patients (high cervical cord injury, n = 5; central
      hypoventilation following neurosurgery, n = 1; idiopathic acquired central
      hypoventilation, n = 1). INTERVENTION, MEASUREMENTS, AND RESULTS:
      Electromyography of the diaphragm and transdiaphragmatic pressure were assessed
      in response to CxMS and CMS. In three cases, no interruption of the
      corticodiaphragmatic pathway was evidenced, the decision of pacing was postponed,
      and the patients eventually recovered a spontaneous breathing activity. In two
      cases, the diagnosis of irreversible peripheral phrenic dysfunction was reached
      and pacing was denied. In two cases, complete interruption of the
      corticodiaphragmatic pathway and integrity of peripheral conduction led to the
      decision of phrenic pacemaker implantation. CONCLUSION: CxMS and CMS can be used
      to refine the assessment of patients proposed for phrenic pacing. CxMS can
      possibly identify those in whom there is a possibility for eventual recovery, and
      therefore substantiate a decision to postpone the pacing.

PMID- 8989077
TI  - Early diagnosis of ventilator-associated pneumonia. Is it possible to define a
      cutoff value of infected cells in BAL fluid?
AB  - STUDY OBJECTIVE: To assess the usefulness of quantification of infected cells
      (ICs) in BAL fluid for the diagnosis of ventilator-associated pneumonia (VAP).
      DESIGN: A prospective study. SETTING: A medico-surgical ICU in a tertiary health
      care institution. PATIENTS: One hundred thirty-two patients (mean age, 52 +/- 19
      years). The suspicion of nosocomial pneumonia was strong in these patients: all
      had fever (> or = 38.5 degrees C), purulent tracheal aspirates, leukocytosis (>
      or = 10,000 cells per cubic millimeter), and new or persistent radiographic lung
      infiltrates. INTERVENTIONS: One hundred sixty-three samples (BAL and protected
      specimen brushes [PSB]) were obtained. RESULTS: VAP was present in 56 cases. The
      diagnosis was excluded in the remaining 107 cases. The IC count was performed on
      100 cells in BAL fluid. The percentage of IC was significantly higher (12.6 +/-
      12.4 vs 1.14 +/- 3.39; p < 0.0001) in patients with pneumonia: the area under the
      receiver operating characteristic (ROC) curve was 0.888 and a threshold of 2% of
      IC corresponded to a sensitivity of 84%, a specificity of 80%, a positive
      predictive value of 69%, and a negative predictive value of 90%. CONCLUSIONS: It
      is possible to define a threshold of IC in BAL fluid with a good reliability by
      using an ROC curve. This technique is useful for the early diagnosis (< 2 h) of
      nosocomial bacterial pneumonia in mechanically ventilated patients and allows a
      rapid and appropriate treatment of most of the patients with suspected VAP.

PMID- 8989078
TI  - Criteria for extubation and tracheostomy tube removal for patients with
      ventilatory failure. A different approach to weaning.
AB  - The purpose of this study was to prospectively compare parameters that might
      predict successful translaryngeal extubation and tracheostomy tube decannulation.
      Irrespective of ventilatory function, 62 extubation/decannulation attempts were
      made on 49 consecutive patients with primarily neuromuscular ventilatory
      insufficiency who satisfied criteria. Thirty-four patients required 24-h
      ventilatory support. Noninvasive intermittent positive pressure ventilation
      (IPPV) was substituted as needed for IPPV via translaryngeal or tracheostomy
      tubes. Successful decannulation was defined as extubation or decannulation and
      site closure with no consequent respiratory symptoms or blood gas deterioration
      for at least 2 weeks. Failure was defined by the appearance of respiratory
      distress and decreases in vital capacity and oxyhemoglobin saturation despite use
      of noninvasive IPPV and assisted coughing. The independent variables of age,
      extent of predecannulation ventilator use, vital capacity, and peak cough flows
      (PCF) were studied to determine their utility in predicting successful extubation
      and decannulation. Only the ability to generate PCF greater than 160 L/min
      predicted success, whereas inability to generate 160 L/min predicted the need to
      replace the tube. All 43 attempts on patients with PCF greater than 160 L/min
      succeeded; all 15 attempts on patients with PCF below 160 L/min failed; and of 4
      patients with PCF of 160 L/min, 2 succeeded and 2 failed. We conclude that the
      ability to generate PCF of at least 160 L/min is necessary for the successful
      extubation or tracheostomy tube decannulation of patients with neuromuscular
      disease irrespective of ability to breathe.

PMID- 8989079
TI  - Late complications of percutaneous dilatational tracheotomy.
AB  - STUDY OBJECTIVE: To assess the late complications of percutaneous dilatational
      tracheotomy, particularly the incidence of tracheal stenosis and voice changes.
      DESIGN: Prospective descriptive clinical study. SETTING: Teaching hospital, the
      Netherlands. PATIENTS: Eighty consecutive patients who were successfully
      decannulated after percutaneous tracheotomy. MEASUREMENTS AND RESULTS: Fourteen
      patients died after decannulation, of tracheotomy-unrelated causes. Sixty-six
      patients were followed up 3 to 39 months after decannulation (mean, 16 months).
      Fifty-four patients underwent tomography of the trachea. In 14 patients (26%),
      there was tracheal narrowing of more than 10%. Data analysis showed that these
      stenoses were operator dependent (p = 0.03). Voice changes, found in 13 (21%) of
      61 patients, were major in 1 and minor in 12. Scars were generally cosmetically
      acceptable. Retraction of the scar, seen in 13 (19%) of 66 patients, was related
      to the duration of cannulation (p = 0.002). A persistent tracheocutaneous fistula
      was present in two patients. CONCLUSIONS: The incidence of tracheal stenosis
      after percutaneous dilatational tracheotomy is low compared with conventional
      tracheotomy. Experience with the technique is important to avoid late
      complications.

PMID- 8989080
TI  - Reintubation as an outcome predictor in trauma patients.
AB  - STUDY OBJECTIVE: Determine reintubation rate, identify its cause, and detail
      adverse outcomes from reintubation. DESIGN: Retrospective review of extubation
      failures in the trauma ICU. SETTING: University hospital and regional trauma
      center. PATIENTS: Four hundred five patients arriving intubated or requiring
      intubation during hospitalization after 2,516 traumatic injury admissions over 18
      months. INTERVENTIONS: None. RESULTS: Reintubation incidence was 7% (27 times per
      405 patients). Comparative mortality of the reintubated group (2/24 = 8%) is
      similar to overall trauma center mortality (224/2516 = 6.5%), but less than the
      cohort of patients admitted to the hospital intubated (63/405 = 16%). Reintubated
      patients had an increased frequency of stridor than reported previously (33%),
      and an increased tracheostomy rate (62% vs 30%). Stridor was not predictable from
      injury severity score, Glasgow coma score, age, sex, length of intubation, or
      place of intubation. Pulmonary complications (atelectasis, tracheobronchitis,
      pneumonia) developed in half of reintubated patients; stridorous patients did not
      have an increased rate of pulmonary complications. CONCLUSION: Reintubation in
      trauma ICU patients does not predict poor outcome.

PMID- 8989081
TI  - Nocturnal noninvasive positive pressure ventilatory assistance.

PMID- 8989082
TI  - Asthma: better outcome at lower cost? The role of the expert in the care system.
AB  - Asthma is a common disease for which morbidity and mortality have been
      increasing. This despite advances in the scientific understanding of asthma and
      in the pharmacologic armamentarium available to treat it. The dichotomy between
      knowledge and outcomes led us to review asthma from a systems perspective. We
      have presented data first to document failure in the current system of care and
      then to examine factors associated with improved outcomes. We found a disparity
      in outcome and costs when care given by experts was contrasted with care given by
      generalists. We conclude that "expert-based" care systems are superior from the
      perspective both of the patient and of the insurer; medical outcomes are better
      at lower overall cost. Managed care companies are in a unique position to
      identify asthmatics and to shift them from generalist to expert-based care when
      appropriate.

PMID- 8989083
TI  - Controversies in sleep disorders medicine. Pulmonologists respond!
AB  - PURPOSE: Herein we report the results of an informal survey of approximately 350
      physicians attending the American College of Chest Physicians meeting in October
      1995. METHODS: With response computer technology, we polled session participants
      about sleep and sleep disorders. The responses to the questions were
      instantaneously displayed and recorded and are presented herein. RESULTS: We
      found considerable expertise and experience in our audience; 65% were board
      certified in pulmonary medicine and 12% in sleep disorders medicine. There was
      not agreement about expectations upon referral of a patient to a sleep center or
      about the definitions of either sleep apnea or hypopnea. Most sleep centers
      perform split-night polysomnography but there is not a single clear indication
      for this procedure and there is uncertainty about the efficacy of split-night
      studies. Most laboratories represented recognize the diagnosis of upper airways
      resistance syndrome, and respondents seemed well versed in the definition of this
      entity. There was not uniform agreement of the treatment effects of mild or
      positional obstructive sleep apnea. CONCLUSIONS: Pulmonologists appear to be
      interested in and knowledgeable about sleep disorders. There are several basic
      areas of controversy, emphasizing the need for clinical research in the area of
      sleep-disordered breathing.

PMID- 8989084
TI  - Video-assisted cardiac surgery. Preliminary experience in reoperative mitral
      valve surgery.
AB  - OBJECTIVES: Video-assisted endoscopic techniques had been applied in the surgical
      correction of patent ductus arteriosus, vascular ring, or coronary artery
      disease. However, it has been used only recently in the correction of reoperative
      mitral valve lesions. DESIGN: Video-assisted cardiac operations were performed on
      four patients who had received surgical interventions on their mitral valves and
      needed emergent reoperation. PATIENTS: Four patients (3 men and 1 woman) received
      emergency surgery from September to December 1995 for thrombosis of mechanical
      mitral prosthesis (2 patients) and severe mitral regurgitation with previously
      failed mitral valve repair (2 patients). Six previous operations had been
      performed on these mitral valves. Patient ages ranged from 26.7 to 68.1 years
      (mean, 47.3 years). Preoperatively, acute pulmonary edema occurred in two
      patients, cerebral emboli occurred in one patient, and sepsis was found in one
      patient. Mechanical ventilatory support was used in two patients before
      operation. INTERVENTION: The operations were performed through right anterior
      minithoracotomy, guided by video-assisted endoscopic techniques with femoro
      femoral extracorporeal circulation. The operative procedures were thrombectomy of
      mitral prosthesis in two patients, mitral valve repair in one patient, and mitral
      valve replacement in one patient. RESULTS: The duration of extracorporeal
      circulation was 166 to 320 min (222 +/- 67 min) and the operation time was 4.6 to
      6.8 h (6.1 +/- 1.0 h). All patients recovered from the operations rapidly with
      uneventful postoperative courses except 1 patient who had sepsis preoperatively
      and died 2 months later. CONCLUSION: Our experience demonstrates that video
      assisted cardiac surgery is technically feasible and could be performed in
      reoperation of the mitral valve.

PMID- 8989085
TI  - Progressive shortness of breath in a 50-year-old man with ulcerative colitis.

PMID- 8989086
TI  - A patient with cerebral arteriovenous malformation and multiple metallic
      pulmonary particles.

PMID- 8989087
TI  - An asthmatic becomes hypotensive on mechanical ventilator support.

PMID- 8989088
TI  - Effect of posture on the flow-volume loop in two patients with euthyroid goiter.
AB  - In two patients with a goiter and respiratory symptoms occurring only in the
      recumbent posture, flow-volume loops (FVLs) were performed in various body
      postures: while sitting upright, supine, and left and right lateral decubitus. In
      both patients, flow rates, upper airway obstruction indices, and FVL morphologic
      features with patients in recumbent postures indicated the appearance of upper
      airway flow limitation with patients in the recumbent posture as compared with
      the upright posture. In the one patient who underwent thyroid surgery, these
      posture-related changes disappeared. We conclude that in patients with a goiter
      (or any extrinsic mass near to the upper airway), the comparison of FVLs
      performed in various body positions may help to clarify the origin of posture
      related respiratory symptoms.

PMID- 8989089
TI  - A case of acute eosinophilic pneumonia. Evidence for hypersensitivity-like
      pulmonary reaction.
AB  - We examined an 86-year-old man with acute respiratory failure. A chest
      roentgenogram showed diffuse reticular shadows. Transbronchial biopsy revealed
      thickening of the alveolar septa accompanied by moderate eosinophil infiltration.
      After admission to the hospital, the patient's symptoms immediately improved
      without any medication. Clinical course and pathologic findings suggested acute
      eosinophilic pneumonia caused by a hypersensitivity reaction.

PMID- 8989090
TI  - Get real, Dr. Block.

PMID- 8989091
TI  - Get real, Dr. Block.

PMID- 8989092
TI  - The barbarism of managed care, revisited.

PMID- 8989093
TI  - The barbarism of managed care, revisited.

PMID- 8989094
TI  - The barbarism of managed care, revisited.

PMID- 8989095
TI  - The barbarism of managed care, revisited.

PMID- 8989096
TI  - Alpha 1-proteinase inhibitor (human) shortage.

PMID- 8989097
TI  - Do not forget the pathologist and the cytologist.

PMID- 8989098
TI  - Selective decontamination of the digestive tract. Consider cross-infection of
      Staphylococcus aureus?

PMID- 8989099
TI  - Danny's liberation on independence day.

PMID- 8989100
TI  - From CPR to DNR. The return of death with dignity.

PMID- 8989101
TI  - Cervical collar in sleep apnea.

PMID- 8989102
TI  - Congress passes incremental healthcare reform.

PMID- 8989103
TI  - Meeting highlights XVIIIth Congress of the European Society of Cardiology, August
      25-29, 1996.

PMID- 8989104
TI  - Effect of pravastatin on coronary events after myocardial infarction in patients
      with average cholesterol levels.

PMID- 8989105
TI  - Hibernating myocardium has reduced blood flow at rest that increases with low
      dose dobutamine.
AB  - The study of Sun and coworkers is important because (1) it provides additional
      data that HM has an inotropic and an attenuated coronary vasodilator reserve.
      They also provided data that support the conclusion that with dobutamine, the
      improvement of abnormal LV wall motion is real in many patients. (2) It
      emphasizes the possibility of a deleterious effect (infarction) of dobutamine in
      HM and thus the need for appropriate caution during its use. (3) It provides
      additional data that confirm that areas of perfusion-metabolism mismatch on PET
      imaging (HM) are associated with a reduced MBF at rest. However, their
      conclusions about areas of LV dysfunction with "normal" MBF in coronary artery
      disease are problematic; therefore, one must be extremely cautious about these
      conclusions on the basis of the data that are presented.

PMID- 8989106
TI  - A little VEGF goes a long way. Therapeutic angiogenesis by direct injection of
      vascular endothelial growth factor-encoding plasmid DNA.
AB  - Nevertheless, the simplicity of using injections of naked plasmid DNA into
      skeletal muscle tissue as an effective means to deliver a potent, secreted
      angiogenesis factor into ischemic peripheral vascular beds is both an exciting
      and encouraging finding. It is estimated that 150,000 patients per year require
      lower-limb amputations for ischemic peripheral vascular disease in the United
      States. The impressive progress being made toward the use of VEGF gene therapy
      for effective therapeutic angiogenesis in ischemic peripheral vascular disease is
      truly welcome news for clinicians faced with the task of providing care for those
      patients suffering from lower-limb vascular insufficiency.

PMID- 8989108
TI  - A 'BOLD' new approach to renal oxygen economy.

PMID- 8989107
TI  - Angiogenic gene therapy. A leg to stand on?

PMID- 8989109
TI  - Codon 102 of the cardiac troponin T gene is a putative hot spot for mutations in
      familial hypertrophic cardiomyopathy.
AB  - BACKGROUND: Familial hypertrophic cardiomyopathy is a phenotypically and
      genetically heterogeneous disease. In some families, the disease is linked to the
      CMH2 locus on chromosome 1q3, in which the cardiac troponin T gene (TNNT2) has
      been identified as the disease gene. The mutations found in this gene appear to
      be associated with incomplete penetrance and poor prognosis. Because mutational
      hot spots offer unique possibilities for analysis of genotype-phenotype
      correlations, new missense mutations that could define such hot spots in TNNT2
      were looked for in unrelated French families with familial hypertrophic
      cardiomyopathy. METHODS AND RESULTS: Family members were genotyped with
      microsatellite markers to detect linkage to the four known disease loci. In
      family 715, analyses showed linkage to CMH2 only. To accurately position
      potential mutations on TNNT2, its partial genomic organization was established.
      Screening for mutations was performed by single-strand conformation polymorphism
      analysis and sequencing. A new missense mutation, Arg102Leu, was identified in
      affected members of family 715 because of a G-->T transversion located in the
      10th exon of the gene. Penetrance of this new mutation is complete;
      echocardiographic data show a wide range of hypertrophy; and there was no sudden
      cardiac death in this family. CONCLUSIONS: The codon 102 of the TNNT2 gene is a
      putative mutational hot spot in familial hypertrophic cardiomyopathy and is
      associated with phenotypic variability. Analysis of more pedigrees carrying
      mutations in this codon is necessary to better characterize the clinical and
      prognostic implications of TNNT2 mutations.

PMID- 8989110
TI  - Common mutation in methylenetetrahydrofolate reductase. Correlation with
      homocysteine metabolism and late-onset vascular disease.
AB  - BACKGROUND: Increased homocysteine levels are a risk factor for atherosclerosis
      and its sequelae. A common genetic mutation in methylenetetrahydrofolate
      reductase (MTHFR), an enzyme required for efficient homocysteine metabolism,
      creates a thermolabile enzyme with reduced activity. We determined the prevalence
      of this mutation in many subjects with and without vascular disease and related
      it to homocysteine and folate levels. METHODS AND RESULTS: DNA from 247 older
      subjects with vascular disease and 594 healthy subjects without vascular disease
      (in three different control groups) was screened for the MTHFR 677 C-to-T
      mutation. Within each group, 9% to 17% of the subjects were homozygous for this
      mutation, and the mutant allele frequency was 31% to 39%. The genotype
      distributions, homozygote frequencies, and allele frequencies did not differ
      significantly between the study groups. In the vascular disease subjects, despite
      significantly lower folate levels in MTHFR homozygotes, there was no significant
      difference in homocysteine levels among the MTHFR genotype groups. The negative
      slope of the regression line relating homocysteine and folate was significantly
      steeper for those with a homozygous MTHFR mutation compared with those without
      this mutation. CONCLUSIONS: Although the thermolabile MTHFR mutation is very
      common, it does not appear to be a significant genetic risk factor for typical
      late-onset vascular disease. Because MTHFR homozygotes have increased
      homocysteine with low folate levels, this mutation may contribute to early-onset
      or familial vascular disease. The genotype dependence of the folate-homocysteine
      correlation further suggests that homozygotes for this mutation may have both an
      exaggerated hyperhomocysteinemic response to folic acid depletion and a better
      response to folic acid therapy.

PMID- 8989111
TI  - Intimal thickening develops without humoral immunity in a mouse aortic allograft
      model of chronic vascular rejection.
AB  - BACKGROUND: The major threat to the long-term survival of cardiac allograft
      recipients is the development of diffuse intimal thickening in the allograft
      coronary arteries through mechanisms that are poorly understood. Although
      antidonor antibodies have been associated with the development of this condition,
      a causal relationship has not been established. METHODS AND RESULTS: To determine
      whether humoral immune responses are necessary for the development of graft
      vascular disease, we performed abdominal aortic allografts from normal donor mice
      into different immunodeficient recipient mice: those lacking all donor-specific
      immune responses (severe combined immunodeficient [SCID] mice and recombination
      activating gene-1 [RAG-1]-deficient mice) and those lacking humoral immune
      responses alone owing to a targeted deletion of the joining region (JH) gene
      segments for the immunoglobulin heavy chain. At 6 to 9 weeks after
      transplantation, aortic allografts in normal immunocompetent recipients showed
      concentric intimal thickening extending the full length of the graft (percent
      luminal reduction, [%LR], 31.2 +/- 9.1 [mean +/- SD] and 38.5 +/- 3.6 in
      different donor-recipient strain combinations). In contrast, syngeneic
      (histocompatible) aortic grafts showed a normal-appearing vessel wall (%LR, 1.6
      +/- 0.7). In both SCID and RAG-1-deficient recipients, aortic allografts showed a
      virtual absence of neointimal formation (%LR, 3.7 +/- 2.1 and 3.8 +/- 1.6 in SCID
      and RAG-1-deficient recipients, respectively), indicating a critical etiological
      role for alloimmune responses in this model. Importantly, allografts in JH
      deficient mice showed marked intimal thickening (%LR, 35.7 +/- 7.9), with an
      appearance histologically indistinguishable from that of normal immunocompetent
      recipients. CONCLUSIONS: Neointimal formation in graft vascular disease is
      critically dependent on alloimmune responses of the host. Humoral effector
      mechanisms, however, may not be required.

PMID- 8989112
TI  - Immunocytochemical localization of rH1 sodium channel in adult rat heart atria
      and ventricle. Presence in terminal intercalated disks.
AB  - BACKGROUND: Of the five sodium channel subtypes expressed in cardiac tissues, the
      rat (rH1) and human (hH1) isoforms are thought to be the predominant subtypes on
      the basis of heterologous expression studies. In this study, subtype-specific
      antibodies and immunocytochemistry were used to confirm protein expression and to
      localize rH1 protein in cardiac tissues. METHODS AND RESULTS: Subtype-specific
      antibodies immunolabeled adult rat heart tissue in a manner identical to that
      obtained with subtype-nonselective antibodies. All antibodies specifically bound
      to the surface and t-tubular systems of atrial and ventricular muscle cells.
      Cytoplasmic labeling, reflecting nascent sodium channels or cytoplasmic stores of
      sodium channel protein, was apparent. Most notably, all antibodies also
      specifically labeled the subset of intercalated disks located at the ends but not
      the sides of adjacent ventricular muscle cells. CONCLUSIONS: rH1 is the
      predominant subtype expressed on rat atrial and ventricular muscle cells. rH1
      protein localization in surface and t-tubular membranes is consistent with its
      proposed role in coordinating membrane depolarization along the length and deep
      within cardiac muscle cells. rH1 protein localization in terminal intercalated
      disks suggests that sodium channels may also act as a localized voltage-dependent
      current amplifier, raising the safety margin for conduction; they also may
      contribute to anisotropic or saltatory conduction in cardiac tissues. These
      electrophysiological properties would be particularly important under conditions
      of altered, channel function resulting from ion channel gene defects (e.g., long
      QT syndrome), antiarrhythmic drug therapy, ischemia, or other heart diseases by
      influencing the electrophysiological substrate for ventricular tachyarrhythmias.

PMID- 8989113
TI  - Opposite effects of angiotensin AT1 and AT2 receptor antagonists on recovery of
      mechanical function after ischemia-reperfusion in isolated working rat hearts.
AB  - BACKGROUND: Angiotensin II type 1 (AT1) receptor antagonists, when given over the
      long term, reduce the deleterious consequences of ischemia-reperfusion injury.
      Whether short-term administration of AT1 or angiotensin II type 2 (AT2) receptor
      antagonists is cardioprotective has not been investigated. METHODS AND RESULTS:
      The effects of short-term administration of selective AT1 and AT2 receptor
      antagonists on the recovery of mechanical function during reperfusion after 30
      minutes of global, no-flow ischemia were studied in left atrium-perfused isolated
      working rat hearts. Control hearts (n = 8) showed incomplete recovery of left
      ventricular minute work (LV work) and cardiac efficiency during reperfusion to 51
      +/- 15% and 61 +/- 19% of preischemic levels, respectively. Compared with control
      hearts, the selective AT2 receptor antagonist PD123,319 (0.3 mumol/L) given
      before ischemia (n = 7) improved the recovery of LV work and efficiency to 82 +/-
      4% and 98 +/- 7% of preischemic levels, respectively (P < .01). In contrast, the
      selective AT1 antagonist losartan (1 mumol/L) blocked the recovery of LV work and
      depressed efficiency to 0 +/- 0% and 1 +/- 0% (n = 7) of preischemic levels,
      respectively (P < .01; n = 7). Neither antagonist altered coronary vascular
      conductance. CONCLUSIONS: This is the first demonstration that short-term
      treatment with a selective AT1 versus AT2 antagonist exerts different effects on
      recovery of mechanical function after ischemia-reperfusion: the AT2 antagonist
      was cardioprotective, whereas the AT1 antagonist was not. These data suggest that
      AT2 antagonists and AT1 agonists may offer novel approaches for the treatment of
      mechanical dysfunction after ischemia-reperfusion.

PMID- 8989114
TI  - Macrophages, smooth muscle cells, and tissue factor in unstable angina.
      Implications for cell-mediated thrombogenicity in acute coronary syndromes.
AB  - BACKGROUND: Macrophage expression of tissue factor may be responsible for
      coronary thrombogenicity in patients with plaque rupture. In patients without
      plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study
      was designed to identify the cellular correlations of tissue factor in patients
      with unstable angina. METHODS AND RESULTS: Tissue from 50 coronary specimens
      (1560 pieces) from patients with unstable angina and 15 specimens from patients
      with stable angina were analyzed. Total and segmental areas (in square
      millimeters) were identified with trichrome staining. Macrophages, smooth muscle
      cells, and tissue factor were identified by immunostaining. Tissue factor content
      was larger in unstable angina (42 +/- 3%) than in stable angina (18 +/- 4%) (P =
      .0001). Macrophage content was also larger in unstable angina (16 +/- 2%) than in
      stable angina (5 +/- 2%) (P = .002). The percentage of tissue factor located in
      cellular areas was larger in coronary samples from patients with unstable angina
      (67 +/- 8%) than in samples from patients with stable angina (40 +/- 5%) (P =
      .00007). Multiple linear stepwise regression analysis showed that coronary tissue
      factor content correlated significantly (r = .83, P < .0001) with macrophage and
      smooth muscle cell areas only in tissue from patients with unstable angina, with
      a strong relationship between tissue factor content and macrophages in the
      atheromatous gruel (r = .98, P < .0001). CONCLUSIONS: Tissue factor content is
      increased in unstable angina and correlates with areas of macrophages and smooth
      muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute
      coronary syndromes.

PMID- 8989115
TI  - Macrophage infiltration predicts restenosis after coronary intervention in
      patients with unstable angina.
AB  - BACKGROUND: Restenosis remains the major limitation of percutaneous coronary
      revascularization. Macrophages release cytokines, metalloproteinases, and growth
      factors that may induce smooth muscle cell migration and proliferation. We tested
      the hypothesis that primary lesions that develop restenosis after coronary
      atherectomy have more macrophages and smooth muscle cells than primary lesions
      that do not develop restenosis. METHODS AND RESULTS: Fifty patients with unstable
      angina were identified. Total and segmental areas were quantified on trichrome
      stained sections of coronary atherectomy tissue. Macrophages and smooth muscle
      cells were identified by immunohistochemical staining. Restenosis, defined as >
      50% stenosis diameter by quantitative cineangiography, was present in 30
      patients. The other 20 patients (< 50% stenosis) constitute the "no restenosis"
      group. The percentages of smooth muscle cell areas were similar in specimens from
      patients with and without restenosis (57 +/- 5% and 52 +/- 6%) (P = NS). However,
      macrophage-rich areas were larger in plaque tissue from patients with restenosis
      (20.4 +/- 2%) than in tissue from patients without restenosis (9.3 +/- 2%) (P =
      .0007). Multiple stepwise logistic regression analysis identified macrophages as
      the only independent predictor for restenosis (P = .006). CONCLUSIONS:
      Macrophages are increased in coronary atherectomy tissue from primary lesions
      that develop restenosis, suggesting a possible role for macrophages in the
      restenotic process after percutaneous coronary intervention.

PMID- 8989116
TI  - C-type natriuretic peptide in human coronary atherosclerotic lesions.
AB  - BACKGROUND: C-type natriuretic peptide (CNP) belongs to the natriuretic peptide
      family and is considered to have regulatory effects on vascular tone and smooth
      muscle growth. Since these features play a role in atherogenesis, the presence of
      CNP at such sites was studied. METHODS AND RESULTS: Thirty-three coronary artery
      segments were harvested at autopsy: 10 normal, with diffuse intimal thickening,
      and 23 atherosclerotic lesions. Samples were snap-frozen and processed for
      immunohistochemical staining. For the identification of CNP, a mouse monoclonal
      antibody (KY-CNP-1) was used. 1A4, EBM-11 (CD68), and von Willebrand factor
      antibodies were used to stain smooth muscle cells, macrophages, and endothelial
      cells, respectively. CNP is present in several cell types. Normal arterial
      segments show CNP-positive endothelial cells. Hypercellular atherosclerotic
      lesions show distinct CNP positivity of smooth muscle cells and macrophages but a
      decrease in positivity of endothelial cells. Advanced atherosclerotic lesions
      contain CNP-positive macrophages, but the smooth muscle cells within the fibrous
      cap and the surface endothelial cells are almost all CNP-negative. CONCLUSIONS:
      These observations suggest that CNP has functional significance in atherogenesis.

PMID- 8989117
TI  - Long-term smoking impairs platelet-derived nitric oxide release.
AB  - BACKGROUND: Long-term smoking impairs endothelium-dependent vasodilation, which
      is mediated by nitric oxide (NO). However, it is unknown whether long-term
      smoking impairs the platelet-derived NO release, which regulates platelet
      aggregation. METHODS AND RESULTS: Platelet-derived electrical current induced by
      collagen was measured with an NO-selective electrode in 12 smokers and 11
      nonsmokers. Collagen-induced intraplatelet cGMP and platelet aggregation was
      measured in smokers and nonsmokers. S-nitroso-N-acetyl-dl-penicillamine, a direct
      NO donor, dose dependently increased in electrical current (r = .99). Collagen
      induced platelet aggregation and dose dependently increased electrical current (r
      = .94). Collagen-induced electrical current and cGMP were significantly augmented
      by L-arginine, a precursor of NO, and attenuated by NG-monomethyl-L-arginine, an
      inhibitor of NO synthesis. Significant correlation was found between collagen
      induced electrical current and cGMP (r = .73). These findings indicate that the
      change in electrical current reflects the NO release through the L-arginine-NO
      pathway in platelets. Collagen-induced electrical current (6.7 versus 13.8 pA; P
      < .001) and cGMP (1.2 versus 3.0 pmol/10(9) platelets; P < .005) were
      significantly lower in smokers than in nonsmokers. Although L-arginine increased
      cGMP levels in both smokers and nonsmokers, the level was still lower in smokers
      than in nonsmokers. The inhibitory effect of L-arginine on collagen-induced
      platelet aggregation was significantly lower in smokers than in nonsmokers (P <
      .05). CONCLUSIONS: These findings provide evidence that platelet-derived NO
      release is significantly impaired in long-term smokers, resulting in the
      augmentation of platelet aggregability.

PMID- 8989118
TI  - Angiotensin-converting enzyme inhibition restores flow-dependent and cold pressor
      test-induced dilations in coronary arteries of hypertensive patients.
AB  - BACKGROUND: Cold pressor test (CPT)-induced and flow-dependent epicardial
      coronary artery dilations are impaired in patients with hypertension. ACE
      inhibition can attenuate sympathetic coronary constriction and potentiate or
      restore endothelium-dependent relaxations. This study was designed to determine
      whether the ACE inhibitor perindoprilat can restore normal coronary dilative
      responses in hypertensive patients. METHODS AND RESULTS: Coronary vasomotor
      responses to CPT and to maximal increase of blood flow induced by papaverine were
      studied in 10 untreated patients with essential hypertension, no other risk
      factors, and angiographically normal coronary arteries before and after
      intravenous ACE inhibition by perindoprilat. Diameters of proximal and distal
      left anterior descending (LAD) and circumflex coronary arteries were measured by
      quantitative angiography. Estimates of coronary blood flow and resistance index
      were calculated with an intracoronary Doppler catheter in the distal LAD.
      Perindoprilat did not modify the hemodynamic responses to CPT and papaverine. In
      response to CPT, perindoprilat changed the epicardial coronary constriction (-8.4
      +/- 5.8%, P < .001) into a significant dilation (+12.0 +/- 6.4%, P < .001).
      Perindoprilat significantly increased the coronary blood flow (from 33.7 +/- 10.0
      to 57.9 +/- 20.5 mL/min, P < .01) and enhanced the decrease in coronary
      resistance (from 4.28 +/- 1.27 to 2.96 +/- 0.84 mm Hg.mL-1.min-1, P < .001)
      caused by CPT. Flow-dependent dilation of the proximal LAD was abolished in the
      control condition and was restored after perindoprilat (12.6 +/- 4.7%, P < .001).
      CONCLUSIONS: ACE inhibition restored CPT-induced and flow-mediated coronary
      artery dilations in patients with essential hypertension. These results indicate
      that impaired coronary vasomotor responses may be reversible in recently
      diagnosed hypertension.

PMID- 8989119
TI  - Depression, psychotropic medication, and risk of myocardial infarction.
      Prospective data from the Baltimore ECA follow-up.
AB  - BACKGROUND: There is suggestive evidence that depression increases risk of
      myocardial infarction (MI), but there are no prospective studies in which the
      measure of depression corresponds to clinical criteria. This study examines
      prospectively whether a major depressive episode increases the risk of incident
      MI and evaluates the role of psychotropic medication use in this relationship.
      METHODS AND RESULTS: The study is based on a follow-up of the Baltimore cohort of
      the Epidemiologic Catchment Area Study, a survey of psychiatric disorders in the
      general population. A history of major depressive episode, dysphoria (2 weeks of
      sadness), and psychotropic medication use were assessed in 1981, and self
      reported MI was assessed in 1994. Sixty-four MIs were reported among 1551
      respondents free of heart trouble in 1981. Compared with respondents with no
      history of dysphoria, the odds ratio for MI associated with a history of
      dysphoria was 2.07 (95% CI, 1.16 to 3.71), and the odds ratio associated with a
      history of major depressive episode was 4.54 (95% CI, 1.65 to 12.44), independent
      of coronary risk factors. In multivariate models, use of barbiturates,
      meprobamates, phenothiazines, and lithium was associated with an increased risk
      of MI, whereas use of tricyclic antidepressants and benzodiazepines was not.
      Among individuals with no history of dysphoria, only lithium use was
      significantly associated with MI. CONCLUSIONS: These data suggest that a history
      of dysphoria and a major depressive episode increase the risk of MI. The
      association between psychotropic medication use and MI is probably a reflection
      of the primary relationship between depression and MI.

PMID- 8989120
TI  - Decline of coronary heart disease mortality in Finland during 1983 to 1992: roles
      of incidence, recurrence, and case-fatality. The FINMONICA MI Register Study.
AB  - BACKGROUND: The rate of coronary heart disease (CHD) mortality in eastern Finland
      has been the highest in the world. The official mortality statistics suggest,
      however, that is has declined by 60% during the past 20 years. The aim of the
      present study was to examine the contributions of incidence, recurrence, and case
      fatality of coronary events to the trends in CHD mortality in three areas of
      Finland. METHODS AND RESULTS: Population-based myocardial infarction registers
      have been operating in the provinces of North Karelia and Kuopio in eastern
      Finland and the Turku/Loimaa area in southwestern Finland from 1983 to 1992.
      During this 10-year period, each suspected coronary event in persons 35 to 64
      years of age was evaluated for registration. Of these, 13,566 fulfilled the
      criteria of myocardial infarction or coronary death. Almost one fourth (22.4%) of
      the coronary events were sudden, out-of-hospital deaths. Among men, the average
      change in mortality was -7.1% per year (95% confidence interval, -8.4% to -5.8%)
      in North Karelia, -5.0% per year (-7.0% to -3.0%) in Kuopio, and -4.9% per year (
      8.2% to -1.6%) in Turku/Loimaa. Among women, the corresponding changes were -5.6%
      (-11.1% to -0.1%), -4.4% (-8.1% to -0.7%), and -8.1% (-13.0% to -3.2%). In
      eastern Finland, the decline in CHD mortality was due to a decline in recurrent
      coronary events but also in the incidence of first coronary events, whereas in
      southwestern Finland, the decline in case-fatality rate had the major role.
      CONCLUSIONS: The decline in CHD mortality rate in Finland appears to be the
      result of a successful combination of primary and secondary prevention measures
      and improvements in acute coronary care.

PMID- 8989121
TI  - Effect of hypertension and cardiac hypertrophy on coronary artery morphology in
      sudden cardiac death.
AB  - BACKGROUND: Epidemiological studies have shown that hypertension and left
      ventricular hypertrophy (LVH) increase the risk of sudden cardiac death (SCD) in
      patients with severe coronary artery disease (CAD). However, autopsy studies
      comparing the morphological substrates for SCD in normotensives and hypertensives
      are lacking. METHODS AND RESULTS: Heart weight and coronary plaque morphology
      were prospectively compared in SCD in 36 hypertensive and 63 normotensive
      individuals. The frequency of CAD was similar in hypertensives (69%, n = 25) and
      normotensives (73%, n = 46). In 71 hearts with CAD, acute coronary thrombi were
      present in 76% of normotensives versus 36% of hypertensives (P = .002), LVH was
      present in 64% of hypertensives versus 33% of normotensives (P = .01) and in 72%
      of hypertensives with one-vessel disease versus 17% of normotensives with one
      vessel disease (P = .0005), and a healed or acute infarct without acute thrombus
      was present in 36% of hypertensives versus 9% of normotensives (P = .007). Heart
      weight was higher in all cases of plaque rupture (519 +/- 109 g) than eroded
      plaque (381 +/- 92 g, P = .0002). In contrast to hypertensives, normotensive
      hearts with severe CAD showed a stepwise increase in heart weight with one-, two
      , and three-vessel disease (P = .01). CONCLUSIONS: Severe CAD is present in most
      SCD in hypertensive and normotensive individuals, but acute thrombi are more
      common in normotensives. LVH is an important contributing mechanism of SCD in
      hypertensives, especially in cases of one-vessel disease. LVH is associated with
      plaque rupture and extent of disease in SCD in normotensives with severe CAD.

PMID- 8989123
TI  - Influence of isoproterenol and ouabain on excitation-contraction coupling, cross
      bridge function, and energetics in failing human myocardium.
AB  - BACKGROUND: In patients with heart failure, long-term treatment with
      catecholamines and phosphodiesterase inhibitors, both of which increase cyclic
      AMP levels, may be associated with increased mortality, whereas mortality may not
      be increased with glycoside treatment. Differences in clinical benefit between
      cyclic AMP-dependent inotropic agents and cardiac glycosides may be related to
      differences of these drugs on calcium cycling and myocardial energetics. METHODS
      AND RESULTS: Isometric heat and force measurements were used to investigate the
      effects of isoproterenol and ouabain on myocardial performance, cross-bridge
      function, excitation-contraction coupling, and energetics in myocardium from end
      stage failing human hearts. Isoproterenol (1 mumol/L) increased peak twitch
      tension by 55% and decreased time to peak tension and relaxation time by 30% and
      26%, respectively (P < .005). Ouabain (0.38 +/- 0.11 mumol/L) increased peak
      twitch tension and relaxation time by 41% and 20%, respectively, and decreased
      time to peak tension by 12% (P < .05). With isoproterenol, the amount of
      excitation-contraction coupling-related heat evolution (tension-independent heat)
      increased by 246% (P < .05) and the economy of excitation-contraction coupling
      decreased by 61% (P < .05). Ouabain increased tension-independent heat by only
      61% (P < .05) and did not significantly influence economy of excitation
      contraction coupling. The effects of isoproterenol on excitation-contraction
      coupling resulted in a 21% (P < .005) decrease of overall contraction economy,
      which was not significantly changed with ouabain. Neither isoproterenol nor
      ouabain influenced energetics of cross-bridge cycling or recovery metabolism.
      CONCLUSIONS: Major differences between the effects of isoproterenol and ouabain
      in failing human myocardium are related to calcium cycling with secondary effects
      on myocardial energetics.

PMID- 8989122
TI  - Effects of dobutamine stimulation on myocardial blood flow, glucose metabolism,
      and wall motion in normal and dysfunctional myocardium.
AB  - BACKGROUND: This investigation examines the effects of inotropic stimulation on
      myocardial blood flow (MBF) and glucose metabolism (MRGlc) in dysfunctional
      myocardium through the use of positron emission tomography (PET). METHODS AND
      RESULTS: Nineteen patients with chronic coronary artery disease and 12 normal
      volunteers were studied with 13N-ammonia, 18F-deoxyglucose, and PET and with two
      dimensional echocardiography at baseline and during intravenous dobutamine (5 to
      10 micrograms/kg per minute). At rest, MBF in mismatch regions (n = 10) averaged
      0.53 +/- 0.19 mL/g per minute and increased by 41.4 +/- 46.6% (P = .01) during
      dobutamine, whereas in match regions (n = 16) MBF was 0.28 +/- 0.09 mL/g per
      minute at rest without an increase during dobutamine (26.4 +/- 47.3%; NS).
      Myocardium with normal rest MBF was classified as normal remote (normal wall
      motion, n = 8) or abnormal remote (abnormal wall motion, n = 11). Dobutamine
      raised MBF similarly in normal subjects and in normal remote regions (by 82 +/-
      85% and 84 +/- 42%, P < .01) but by only 33 +/- 34% in abnormal remote regions.
      MRGlc declined by 49 +/- 28% (P < .005) with dobutamine in the normal subjects,
      remained unchanged in normal and abnormal remote regions of the patients, but
      increased in mismatch and match regions (by 49 +/- 74% and 46 +/- 77%; P < .05).
      Wall motion improved with dobutamine only in mismatch and abnormal remote regions
      but not in match regions. CONCLUSIONS: Blood flow-metabolism mismatch patterns
      are not consistently associated with a fixed downregulation of MBF; the increased
      contractile work in response to dobutamine stimulation is associated with an
      increase in MBF and a greater reliance on glucose utilization, possibly
      reflecting acute ischemia or alterations in substrate selection by chronically
      dysfunctional myocardium. Importantly, functionally impaired though normally
      perfused myocardium frequently exists in chronic coronary artery disease patients
      and may represent repetitively stunned or, more likely, remodeled left
      ventricular myocardium.

PMID- 8989124
TI  - Cardiac sympathetic responses to acute vasodilation. Normal ventricular function
      versus congestive heart failure.
AB  - BACKGROUND: Although there is indirect evidence of impaired baroreflex control of
      sympathetic outflow directed at heart muscle, the regulation of cardiac
      sympathetic activity in the setting of heart failure is largely unexplored. We
      used the norepinephrine spillover method to address the hypothesis that
      baroreflex control of cardiac sympathetic activity is reduced in heart failure.
      METHODS AND RESULTS: Twenty-three patients were studied, 17 in a group with heart
      failure and 6 in a group with normal ventricular function. In both groups,
      cardiac norepinephrine spillover was assessed in response to nitroprusside
      infused to steady-state conditions. Nitroprusside resulted in significant
      reductions in mean systemic arterial pressure (normal group, -15 +/- 3% [mean +/-
      SEM]; heart failure group, -13 +/- 1%) and mean pulmonary artery pressure (normal
      group, -25 +/- 10%; heart failure group, -29 +/- 4%). In response to
      nitroprusside, there was a 98 +/- 16% increase in cardiac norepinephrine
      spillover in the normal group (from 81 +/- 10 to 159 +/- 25 pmol/min, P < .05).
      Despite similar hemodynamic responses to nitroprusside in the heart failure
      group, there was only a 28 +/- 14% increase in cardiac spillover (from 211 +/- 71
      to 245 +/- 59 pmol/ min, P = NS), a response that was significantly smaller than
      that seen in the normal group. CONCLUSIONS: In patients with heart failure
      compared with subjects with normal ventricular function, there was a
      significantly smaller increase in cardiac sympathetic activity in response to a
      steady-state infusion of nitroprusside. This result provides evidence for reduced
      baroreflex control of cardiac sympathetic activity in heart failure.

PMID- 8989125
TI  - Myocardial involvement is very frequent among patients affected with subclinical
      Becker's muscular dystrophy.
AB  - BACKGROUND: Several cases of Becker's muscular dystrophy (BMD) have been
      reported, which showed mild or subclinical skeletal muscle involvement with an
      overt dilated cardiomyopathy. Here, for the first time, a group of 28 patients
      with BMD who had a subclinical or benign myopathy have been studied through a
      thorough cardiological assessment. METHODS AND RESULTS: Each patient underwent
      ECG and echocardiographic examinations. Molecular analyses of the dystrophin gene
      and protein were performed. An unexpectedly high incidence of myocardial
      involvement was observed among patients affected with subclinical (72%) or benign
      (60%) BMD. The cardiac involvement appears to develop early from the right
      ventricle. Both the increase in left ventricular end-diastolic volume and the
      reduction in the ejection fraction appeared to be age related. Severe left
      ventricular dilation with reduced ejection fraction, which could be complicated
      by life-threatening arrhythmias, may occur. Contrary to previous reports, which
      indicated the involvement of 5'-end mutations in cardiomyopathies as a result of
      dystrophin gene alterations, this study shows that despite the apparent
      concentration of deletions in two regions (5'-end and exons 47 through 49), no
      general conclusions can be drawn regarding the involvement of specific gene
      mutations in the development of cardiomyopathy. CONCLUSIONS: Cardiomyopathy is
      the main clinical feature and complication in patients affected by subclinical or
      mild BMD. The cardiac manifestation is characterized by early right ventricular
      involvement and is later associated with left ventricular impairment. In mild
      BMD, myocardial damage may develop because the patients, who are unaware of a
      possible cardiac involvement, are still able to perform strenuous muscle exercise
      and, through pressure or volume overload, may induce mechanical stress, which is
      harmful for dystrophin-deficient myocardial cells.

PMID- 8989126
TI  - Hemodynamic exercise testing. A valuable tool in the selection of cardiac
      transplantation candidates.
AB  - BACKGROUND: Peak exercise oxygen consumption (Vo2), a noninvasive index of peak
      exercise cardiac output (CO), is widely used to select candidates for heart
      transplantation. However, peak exercise Vo2 can be influenced by noncardiac
      factors such as deconditioning, motivation, or body composition and may yield
      misleading prognostic information. Direct measurement of the CO response to
      exercise may avoid this problem and more accurately predict prognosis. METHODS
      AND RESULTS: Hemodynamic and ventilatory responses to maximal treadmill exercise
      were measured in 185 ambulatory patients with chronic heart failure who had been
      referred for cardiac transplantation (mean left ventricular ejection fraction, 22
      +/- 7%; mean peak Vo2, 12.9 +/- 3.0 mL. min-1.kg-1). CO response to exercise was
      normal in 83 patients and reduced in 102. By univariate analysis, patients with
      normal CO responses had a better 1-year survival rate (95%) than did those with
      reduced CO responses (72%) (P < .0001). Survival in patients with peak Vo2 of >
      14 mL.min-1.kg-1 (88%) was not different from that of patients with peak Vo2 of <
      or = 14 mL.min-1.kg-1 (79%) (P = NS). However, survival was worse in patients
      with peak Vo2 of < or = 10 mL.min-1.kg-1 (52%) versus those with peak Vo2 of > 10
      mL.min-1.kg-1 (89%) (P < .0001). By Cox regression analysis, exercise CO response
      was the strongest independent predictor of survival (risk ratio, 4.3), with peak
      Vo2 dichotomized at 10 mL. min-1.kg-1 (risk ratio, 3.3) as the only other
      independent predictor. Patients with reduced CO responses and peak Vo2 of < or =
      10 mL.min-1.kg-1 had an extremely poor 1-year survival rate (38%). CONCLUSIONS:
      Both CO response to exercise and peak exercise Vo2 provide valuable independent
      prognostic information in ambulatory patients with heart failure. These variables
      should be used in combination to select potential heart transplantation
      candidates.

PMID- 8989127
TI  - Hemodynamic and renal excretory effects of human brain natriuretic peptide
      infusion in patients with congestive heart failure. A double-blind, placebo
      controlled, randomized crossover trial.
AB  - BACKGROUND: The pharmacological effects of infusion of human brain natriuretic
      peptide (hBNP) in patients with severe congestive heart failure have not been
      characterized previously. METHODS AND RESULTS: Twenty patients with severe
      congestive heart failure were randomized in a double-blind, placebo-controlled,
      crossover trial to receive incremental 90-minute infusions of hBNP (0.003, 0.01,
      0.03, and 0.1 microgram/kg per minute) or placebo on 2 consecutive days. At the
      highest completed dose of the hBNP, mean pulmonary artery pressure decreased from
      38.3 +/- 1.6 to 25.9 +/- 1.7 mm Hg; mean pulmonary capillary wedge pressure
      decreased from 25.1 +/- 1.1 to 13.2 +/- 1.3 mm Hg; mean right atrial pressure
      decreased from 10.9 +/- 1 to 4.8 +/- 1.0 mm Hg; mean arterial pressure decreased
      from 85.2 +/- 2.0 to 74.9 +/- 1.7 mm Hg; and cardiac index increased from 2.0 +/-
      0.1 to 2.5 +/- 0.1 L/min per square meter (all P < .01 versus placebo). Urine
      volume and urine sodium excretion increased significantly during hBNP infusion
      when compared with placebo infusion (90 +/- 38 versus 67 +/- 27 mL/h and 2.6 +/-
      2.4 versus 1.4 +/- 1.2 mEq/h, respectively, both P < .05 versus placebo), whereas
      creatinine clearance and urinary potassium excretion did not change. CONCLUSIONS:
      Infusion of incremental doses of hBNP is associated with favorable hemodynamic
      and natriuretic effects in patients with severe congestive heart failure.

PMID- 8989128
TI  - Right ventricular performance and contractile reserve in patients with severe
      heart failure. Assessment by pressure-area relations and association with
      outcome.
AB  - BACKGROUND: Right ventricular (RV) performance appears to be important in
      patients with severe heart failure. Although clinical assessments of RV function
      previously have been limited to load-dependent ejection phase indices, a new
      method has been developed using the relatively load-insensitive concepts of
      pressure-volume relations with automated echocardiographic measures of RV cross
      sectional area as a surrogate for volume. METHODS AND RESULTS: Sixteen patients
      with New York Heart Association functional class IV heart failure and group mean
      left ventricular ejection fraction of 20 +/- 5% were studied. RV pressure-area
      loops were recorded on-line from echocardiographic measures of RV area and high
      fidelity pressure during transient inferior, vena caval balloon occlusions. RV
      contractile reserve was assessed as its functional response to an increase in
      dobutamine from 5.7 +/- 4.1 to 13.1 +/- 4.7 micrograms/kg per minute. Complete
      data sets were available in 13 patients. Group mean RV end-systolic elastance
      (E'es) and maximal elastance (E'max) increased with augmented dobutamine infusion
      (2.9 +/- 1.5 to 5.5 +/- 3.3 mm Hg/cm2 and 3.3 +/- 1.6 to 6.4 +/- 3.9 mm Hg/cm2,
      respectively; P < .01 versus baseline), although individual responses were
      variable. During a 30-day follow-up, 9 patients remained unstable, requiring
      continuous intravenous inotropic therapy; 6 of these had profound deterioration
      requiring mechanical circulatory support. The remaining 4 patients had a
      comparatively good short-term outcome with clinical stability. A 100% increase in
      RV E'es or E'max was associated with a good short-term outcome (P < .05).
      CONCLUSIONS: RV performance can be assessed by pressure-area relations in
      patients with heart failure. RV contractile reserve in response to increases in
      dobutamine was associated with a good short-term outcome and may be of prognostic
      value in patients with severe heart failure.

PMID- 8989129
TI  - Nonsustained ventricular tachycardia in severe heart failure. Independent marker
      of increased mortality due to sudden death. GESICA-GEMA Investigators.
AB  - BACKGROUND: The goal of the study was to determine the prognostic value of
      nonsustained ventricular tachycardia (NSVT) in total mortality in severe
      congestive heart failure (CHF) and in death modes. NSVT is associated with an
      increased mortality in CHF. However, the predictive value of NSVT as a marker for
      sudden death or death due to progressive heart failure has not been determined.
      METHODS AND RESULTS: Five hundred sixteen patients from the GESICA trial (33.4%
      with NSVT) were initially studied with the results of 24-hour Holter and 2 years
      of follow-up. Within 2 years, 87 of 173 patients (50.3%) with NSVT and 106 of 343
      patients (30.9%) without NSVT died. Relative risk (RR) was 1.69 (95% confidence
      interval [CI], 1.27 to 2.24; P < .0002), and Cox proportional hazard analysis was
      1.62 (95% CI, 1.22 to 2.16; P < .001). Sudden death increased from 8.7% (30 of
      343) to 23.7% (41 of 173) in patients with NSVT (RR, 2.77; 95% CI, 1.78 to 4.44;
      P < .001). Progressive heart failure death was also increased from 17.5% (60 of
      343) to 20.8% (36 of 173) (P = .22). Quantitative analysis of 24-hour Holter
      (first 295 patients) demonstrated that couplets had a similar RR to that of NSVT
      for both total mortality (RR, 1.81; 95% CI, 1.22 to 2.66; P < .002) and sudden
      death (RR, 3.37; 95% CI, 1.57 to 7.25; P < .0005). Couplets and/or NSVT
      (ventricular repetitive beats) were even more predictive for sudden death (RR,
      10.1; 95% CI, 1.91 to 52.7; P < .01). CONCLUSIONS: In patients with CHF, NSVT is
      an independent marker for increased overall mortality rate and sudden death. The
      absence of NSVT and ventricular repetitive beats in a 24-hour Holter indicates a
      low probability of sudden death.

PMID- 8989130
TI  - Radiofrequency catheter ablation of atrial flutter. Further insights into the
      various types of isthmus block: application to ablation during sinus rhythm.
AB  - BACKGROUND: Radiofrequency ablation of type 1 atrial flutter (AF1) has recently
      evolved toward an anatomically guided procedure directed to isthmuses at the
      lower part of the right atrium (RA). However, different types of block at these
      isthmuses may be observed and potentially correlated with different late
      outcomes. In addition, because the ablation is anatomically guided, ablation
      should be possible during sinus rhythm. METHODS AND RESULTS: Forty-four patients
      underwent ablation of type 1 AF1 performed during ongoing tachycardia (33
      patients) or sinus rhythm (11 patients). Evidence of inferior vena cava-tricuspid
      annulus isthmus block was assessed by changes in RA impulse propagation while
      pacing from both sides of the ablation site. Apparent complete isthmus block was
      achieved in 43 of 44 patients with 9 +/- 7 pulses. However, incomplete block
      mimicking complete block because of intra-atrial conduction delay but leading to
      a different low RA activation pattern was individualized. At the end of the
      procedure, isthmus block was complete in 35 patients and incomplete in 8, but
      since AF1 reinduction was no longer possible, patients were discharged. During a
      follow-up period of 12.1 +/- 5.5 months, 4 patients experienced AF1 recurrence;
      all had shown incomplete or no block. CONCLUSIONS: Detailed multiple-point low RA
      mapping is necessary to differentiate incomplete from complete isthmus block.
      Complete block is the best marker for long-term success of AF1 ablation, although
      incomplete block may be sufficient to prevent recurrence in a significant number
      of cases. Isthmus block is achievable during sinus rhythm, and AF1 induction is
      not mandatory.

PMID- 8989132
TI  - Epicardial neodymium. YAG laser photocoagulation of ventricular tachycardia
      without ventriculotomy in patients after myocardial infarction.
AB  - BACKGROUND: Surgical ablation of ventricular tachycardia (VT) after myocardial
      infarction has been reported by different endocardial approaches. The
      ventriculotomy may increase mortality of the procedure. METHODS AND RESULTS: We
      report on nine patients who suffered from recurrent VT in the late post
      myocardial infarction period. Significant stenoses were detected in all patients.
      The mean left ventricular ejection fraction was 43.1 +/- 8.3%. Left ventricular
      scar (n = 9) was seen. The mean NYHA class was 2.2 +/- 0.4. Sustained VT (mean
      cycle length, 293 +/- 52 ms) occurred spontaneously (n = 9) and could be induced
      reproducibly. Catheter mapping detected a prematurity of -42 +/- 13 ms in six
      patients. Clinical VT was inducible during surgery in seven patients.
      Middiastolic potentials were detected from the epicardial surface (n = 3), and
      premature potentials were found (n = 8 with prematurity of -108 +/- 46 ms).
      Application of neodymium/yttrium/argon/ garnet (Nd:YAG) laser energy to early
      epicardial activation terminated the arrhythmia (n = 7). Ventriculotomy was not
      performed. Seven patients have been free of VT for a mean follow-up period of 17
      +/- 11 months; one patient relapsed and was treated with an implantable
      cardioverter-defibrillator, as was a second patient with inducible VT after
      surgery. CONCLUSIONS: Surgical Nd:YAG laser photocoagulation of VT on the
      epicardial surface of the heart in post-myocardial infarction patients without
      ventriculotomy is safe and has a high success rate. At the present time, this
      method is recommended in patients with sustained and tolerated VT who need bypass
      surgery. This is the first report on epicardial laser ablation of VT in post
      myocardial infarction VT.

PMID- 8989131
TI  - Inadvertent atrioventricular block during radiofrequency catheter ablation.
      Results of the Pediatric Radiofrequency Ablation Registry. Pediatric
      Electrophysiology Society.
AB  - BACKGROUND: Inadvertent atrioventricular block is a complication of
      radiofrequency ablation. The present study is an analysis of the incidence,
      significance, and factors associated with inadvertent atrioventricular block
      during radiofrequency catheter ablation in childhood and adolescence. METHODS AND
      RESULTS: The records of the Pediatric Radiofrequency Ablation Registry were
      reviewed. Between January 1, 1991, and April 1, 1994, atrioventricular block
      occurred in 23 of 1964 radiofrequency ablations (1.2%): 14 as third-degree block
      (3 transient) and 9 as second-degree block (5 transient). Atrioventricular block
      occurred from 5 seconds to 2 months (mean, 4.1 days; median, 15 seconds) after
      the onset of the energy application. Eight transient cases lasted 1 hour to 1
      month (mean, 9.4 days; median, 7 days). Inadvertent atrioventricular block was
      related to the ablation anatomic site: 3 of 111 (2.7%) anteroseptal, 11 of 106
      (10.4%) midseptal, and 2 of 197 (1.0%) right posteroseptal sites (P = .0007) for
      anteroseptal, P = .0001 for midseptal, and P = .17 for right posteroseptal versus
      nonright septal sites). Five of 314 (1.6%) ablations for atrioventricular nodal
      reentrant tachycardia resulted in atrioventricular block (P = .004 versus
      nonright septal sites). Compared with a matched subgroup, radiofrequency ablation
      experience was the only significant risk factor (32.7 versus 106.6, P = .002) for
      the occurrence of atrioventricular block. CONCLUSIONS: Inadvertent
      atrioventricular block may occur during or late after radiofrequency catheter
      ablation. It is associated with ablations for (1) anterior and midseptal
      accessory pathways and atrioventricular nodal reentry and (2) relative
      institutional inexperience.

PMID- 8989133
TI  - Chronotropic response to exercise. Improved performance of ST-segment depression
      criteria after adjustment for heart rate reserve.
AB  - BACKGROUND: Heart rate (HR) response to exercise plays an important role in the
      diagnosis of coronary artery disease (CAD). Adjustment of ST-segment depression
      for the change in HR with exercise increases the accuracy of the exercise ECG in
      the detection of CAD. In addition, an attenuated HR response to exercise, a
      manifestation of chronotropic incompetence, may have independent diagnostic value
      for CAD. METHODS AND RESULTS: The diagnostic value of adjusting the magnitude of
      ST-segment depression, the ST-segment (ST)/HR index, and the ST/HR slope for
      chronotropic response to exercise was assessed in 283 control subjects and 337
      patients with CAD by dividing each ST measurement by the fraction of HR reserve
      achieved. At a matched specificity of 96%, ST-segment depression of > 160 microV
      identified CAD with a sensitivity of 52%, an ST/HR index of > 1.69 microV/bpm
      identified CAD with a sensitivity of 90%, and an ST/HR slope of > 2.96 microV/bpm
      identified CAD with a sensitivity of 88%. Adjustment for HR reserve improved the
      sensitivity of each method: adjusted ST-segment depression of > 176 had a
      sensitivity of 87% (P < .0001), an adjusted ST/HR index of > 2.14 had a
      sensitivity of 94% (P = .005), and an adjusted ST/HR slope of > 3.47 had a
      sensitivity of 93% (P = .0001). In addition, the 94% and 93% sensitivities of the
      adjusted ST/HR index and ST/HR slope were significantly greater than the 87%
      sensitivity of adjusted ST-segment depression (P < .0001). CONCLUSIONS:
      Correction for an attenuated HR response to exercise improves performance of the
      simple and HR-adjusted ST-segment depression criteria for the identification of
      CAD. These findings support assessment of the degree of chronotropic reserve in
      routine evaluation of the exercise ECG.

PMID- 8989134
TI  - Reduced coronary flow reserve in hypercholesterolemic patients without overt
      coronary stenosis.
AB  - BACKGROUND: Reduced coronary flow reserve (CFR) in hypercholesterolemic patients
      without evidence of ischemia has been reported. However, it remains uncertain
      whether this abnormality occurs without overt coronary atherosclerosis. This
      study aimed to clarify whether CFR is impaired even in anatomically normal
      coronary arteries in hypercholesterolemic patients and to compare CFR between
      familial hypercholesterolemic (FH) patients and secondary hypercholesterolemic
      (SH) patients. METHODS AND RESULTS: Twenty-two patients with hypercholesterolemia
      (11 FH, 11 SH) and 11 control subjects were studied. Baseline myocardial blood
      flow (MBF) and MBF during dipyridamole loading were measured in segments perfused
      by angiographically normal coronary arteries with the use of positron emission
      tomography and 13N-ammonia, and CFR was calculated. Baseline MBF (mL/min per 100
      g heart wt) in FH (81.3 +/- 31.4) and SH (70.0 +/- 20.7) patients was not
      different from that in control subjects (75.0 +/- 34.9). However, MBF during
      dipyridamole loading was significantly lower in FH patients (129 +/- 19.1) than
      in control subjects (322 +/- 174, P < .01) and SH patients (210 +/- 71.2, P <
      .01). CFR in FH patients (1.59 +/- 0.41) was also significantly lower compared
      with both control subjects (4.22 +/- 1.42, P < .01) and SH patients (3.00 +/-
      0.96, P < .01). CFR in SH patients was also significantly lower than that in
      control subjects (P < .05). CFR correlated significantly with both plasma total
      cholesterol (r = .67, P < .01) and LDL cholesterol concentrations (r = .69, P <
      .01). CONCLUSIONS: CFR was decreased even in anatomically normal coronary
      arteries in hypercholesterolemic patients. This abnormality was more prominent in
      FH patients.

PMID- 8989135
TI  - Higher triglycerides, lower high-density lipoprotein cholesterol, and higher
      systolic blood pressure in lipoprotein lipase-deficient heterozygotes. A
      preliminary report.
AB  - BACKGROUND: Heterozygous lipoprotein lipase (LPL) deficiency has been associated
      with familial hypertriglyceridemia and familial combined hyperlipidemia. Studies
      of heterozygotes with LPL gene defects at amino acid residues 188 and 207 showed
      higher triglycerides (TG) and lower HDL cholesterol (HDL-C), with no elevation in
      LDL cholesterol (LDL-C). Other LPL defects may reveal alternate clinical
      phenotypes. METHODS AND RESULTS: We evaluated three families with defects at
      amino acid residues 64, 194, and 188. Thirty-eight heterozygotes (8 with defect
      64, 14 with defect 194, and 16 with defect 188) and 95 family members without
      defects were studied. Plasma lipid, lipoprotein, and apolipoprotein (apo) values
      were measured, as well as blood pressure. Pooled carriers demonstrated higher
      systolic blood pressure (SBP) (127 versus 116 mm Hg, P < .0001) and TG (160
      versus 125 mg/dL, P = .004) and lower HDL-C (44 versus 52 mg/dL, P = .001) than
      did noncarriers. A comparison of the 188 carriers and noncarriers revealed the
      most striking phenotypic characteristics, with lower HDL-C (36 versus 51 mg/dL, P
      < .0001) and HDL-C/(apo A-I + apo A-II) (0.21 versus 0.24, P = .002) and higher
      TG (206 versus 123 mg/dL, P = .0003), SBP (132 versus 116 mm Hg, P = .0004), and
      apo B/LDL-C (1.12 versus 0.93, P < .0001). CONCLUSIONS: These data confirm past
      observations that LPL deficient heterozygotes trend toward lower HDL-C and higher
      TG levels while potentially expressing higher SBP. These data also implicate the
      specific LPL gene defect as a contributing factor to the variable expression of
      HDL-C, TG, and SBP.

PMID- 8989136
TI  - Birth weight and adult hypertension, diabetes mellitus, and obesity in US men.
AB  - BACKGROUND: Low birth weight has been associated with several chronic diseases in
      adults, including hypertension, diabetes mellitus, and obesity. Further study of
      these diseases in a large cohort with information on a wide variety of risk
      factors is essential to determine more precisely the risks associated with birth
      weight. METHODS AND RESULTS: We examined the relation between birth weight and
      cumulative incidence of adult hypertension, incidence of non-insulin-dependent
      diabetes mellitus, and prevalence of obesity in a cohort of 22,846 US men (Health
      Professionals Follow-up Study). Birth weights, medical histories, family
      histories, and other factors were collected by biennial mailed questionnaires.
      Logistic regression was used to examine the association between birth weight and
      these chronic adult diseases. Low birth weight was associated with an increased
      risk of hypertension and diabetes; high birth weight was associated with an
      increased risk of obesity. Compared with men in the referent birth weight
      category (7.0 to 8.4 lb), men who weighed < 5.5 lb had an age-adjusted odds ratio
      for hypertension of 1.26 (95% confidence interval [CI], 1.11 to 1.44) and for
      diabetes mellitus of 1.75 (95% CI, 1.21 to 2.54). There was no material change
      after controlling for adult body mass index and parental histories of
      hypertension and diabetes mellitus. Compared with men in the referent group, the
      age-adjusted odds ratio of being in the highest versus the lowest quintile of
      adult body mass index for men with birth weight > or = 10.0 lb was 2.08 (95% CI,
      1.73 to 2.50). CONCLUSIONS: These findings support the hypothesis that early life
      exposures, for which birth weight is a marker, are associated with several
      chronic diseases in adulthood.

PMID- 8989137
TI  - Quantitative detection of outlet strut separations in Bjork-Shiley convexo
      concave mitral valves.
AB  - BACKGROUND: As of January 31, 1995, 564 outlet strut fractures (OSFs) of Bjork
      Shiley convexo-concave (BSCC) heart valves had been reported to the Shiley Heart
      Valve Research Center, of which approximately two thirds resulted in the death of
      the patient. Previous studies indicate that one leg of the outlet strut separates
      (single-leg separation, SLS) from the valve before the second leg breaks, which
      results in complete OSF. To identify those valves at risk of complete OSF, an in
      vivo radiographic imaging technique is being developed to evaluate the strut leg
      integrity. The goal of the present study was to develop an objective
      postprocessing technique to evaluate outlet strut leg integrity quantitatively in
      these cineradiographic images. METHODS AND RESULTS: Twenty-two sets (12 intact
      valves, 10 SLS valves) of cineangiographic images were obtained from individuals
      whose valve status was subsequently verified ex vivo. Several quantitative
      measures of SLS were evaluated to identify possible loss of metal or gaps in the
      SLS legs. Two of these measures, decrease in pixel intensity (DIPI) ratio and gap
      half-width, are diagnostic metrics of SLS: i.e., the maximum likelihood estimate
      of the area under the receiver operating characteristic curve was 0.892 (SD,
      0.066) for a model based on DIPI ratio and 0.802 (SD, 0.093) for gap half-width.
      CONCLUSIONS: We have developed a postprocessing technique that can be used to
      objectively evaluate outlet strut integrity in cineradiographic images of BSCC
      heart valves. At an estimated specificity of 1.0, the estimated sensitivity of
      the objective review was comparable to that of a subjective expert review panel.

PMID- 8989138
TI  - Association between intima-media thickness and wall shear stress in common
      carotid arteries in healthy male subjects.
AB  - BACKGROUND: Atherosclerotic lesions lie in regions of low wall shear stress. No
      relationship between wall shear stress and intima-media thickness in vivo has
      been reported. Aims of the present study were to verify the reproducibility of
      wall shear stress measurement in vivo and to evaluate its association with intima
      media thickness in the common carotid artery in healthy subjects. METHODS AND
      RESULTS: Wall shear stress was calculated according to the following formula:
      Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter. Blood
      viscosity was measured by use of a cone/plate viscometer. Blood velocity,
      internal diameter, and intima-media thickness were measured by high-resolution
      echo Doppler. Twenty-one healthy male subjects were investigated. Peak and mean
      shear stress values were 29.5 +/- 8.2 and 12.1 +/- 3.1 dynes/cm-2 (mean +/- SD),
      respectively. Peak shear stress was inversely related to intima-media thickness
      (r = .62), age (r = .77), systolic blood pressure (r = .61), and body mass index
      (r = .59) (P < .001 for all coefficients). Mean shear stress yielded similar
      results. The relationship between shear stress and intima-media thickness was
      independent of age, blood pressure, and body mass index. The reproducibility,
      calculated by Kendall's W test, was statistically significant. CONCLUSIONS: Our
      results demonstrate that common carotid artery wall shear stress measurement in
      vivo is reproducible. It inversely relates to intima-media thickness, age,
      systolic blood pressure, and body mass index. These findings confirm in vivo the
      role of shear stress in intima-media thickening.

PMID- 8989139
TI  - Contribution of collagen, elastin, and smooth muscle to in vivo human brachial
      artery wall stress and elastic modulus.
AB  - BACKGROUND: The contributions of collagen, elastin, and smooth muscle to arterial
      mechanical properties in the in vivo human artery are not known. METHODS AND
      RESULTS: We used a recently developed intravascular ultrasound technique to
      measure total brachial artery wall stress and incremental elastic modulus (Einc)
      in seven normal human subjects at baseline and after intra-arterial
      norepinephrine (1.2 micrograms) and nitroglycerin (100 micrograms). Then we
      applied a modified Maxwell model to estimate the elastic modulus of elastin (EE);
      the recruitment of collagen fibers supporting wall stress; and the differential
      contributions of collagen, elastin, and smooth muscle to wall stress and Einc
      over a wide range of pressure and smooth muscle tone. With this model, EE was 3 x
      10(6) dynes/cm2. Collagen fibers were recruited increasingly as transmural
      arterial pressure increased and reached a value of approximately 5% to 6% at 100
      mm Hg under each of the conditions studied. Isobaric smooth muscle contraction
      resulted in a small decrease in total wall stress and no significant change in
      total Einc while shifting the predominant element contributing to these
      mechanical parameters from collagen in parallel with the smooth muscle to
      collagen in series with the smooth muscle. In contrast, isometric smooth muscle
      contraction produced large increases in total wall stress (from 0.11 x 10(6)
      dynes/cm2 after nitroglycerin administration to 1.35 x 10(6) dynes/cm2 after
      norepinephrine administration) and Einc (from 3.84 x 10(6) dynes/cm2 after
      nitroglycerin administration to 57.8 x 10(6) dynes/cm2 after norepinephrine
      administration) entirely as a result of the additional contribution of the smooth
      muscle and its associated series collagen. CONCLUSIONS: This study describes a
      technique for determining arterial elastic properties and a model that can be
      used to estimate a number of mechanical parameters of the human brachial artery
      in vivo. This technique may be useful in studies of the arterial elastic
      properties of arteries in patients with vascular pathology.

PMID- 8989141
TI  - Relationship between type of outflow tract repair and postoperative right
      ventricular diastolic physiology in tetralogy of Fallot. Implications for long
      term outcome.
AB  - BACKGROUND: Restrictive right ventricular (RV) physiology can be present early
      and late after tetralogy of Fallot repair. It is associated with a complicated
      early postoperative course but is favorable late after repair because it is
      associated with less pulmonary regurgitation, better exercise tolerance, and less
      QRS prolongation and symptomatic ventricular arrhythmias. It is not known,
      however, whether in the current surgical era, this physiology is present in
      tetralogy of Fallot patients at mid-term follow-up and whether it is related to
      the type of RV outflow tract repair. Finally, the impact of this physiology on
      the early evolution of QRS prolongation has not been examined previously. In this
      study we attempted to address these issues in a cohort of recently operated
      patients. METHODS AND RESULTS: Ninety-five patients were studied 4.3 years after
      repair by Doppler echocardiography, serial electrocardiograms, and chest
      radiographs. Restrictive RV physiology defined by the presence of antegrade
      pulmonary artery flow in late diastole was present in 38% of the patients. It was
      more common in patients with transannular patch (TAP) repair compared with non
      TAP repair (50% versus 21%, P < .05). QRS duration at follow-up was 121.2 +/-
      17.6 and 132.6 +/- 11.8 ms in restrictive and nonrestrictive patients with TAP
      repair, respectively (P < .02). CONCLUSIONS: Restrictive RV physiology has been
      identified at mid-term follow-up in a contemporary surgical series. It is
      associated with less QRS prolongation, regardless of the technique used for
      outflow tract repair, and may be associated with fewer long-term complications.
      Nonrestrictive physiology is associated with the most marked QRS prolongation.
      This subgroup is most at risk from the late deleterious consequences of chronic
      pulmonary regurgitation.

PMID- 8989140
TI  - Noninvasive evaluation of intrarenal oxygenation with BOLD MRI.
AB  - BACKGROUND: The countercurrent arrangement of capillary blood flow in the medulla
      of mammalian kidneys generates a gradient of oxygen tension between the renal
      cortex and the papillary tip that results in a state of relative hypoxia within
      the renal medulla. Exploration of the pathophysiological implications of
      medullary hypoxia has been hampered by the absence of a noninvasive technique to
      estimate intrarenal oxygenation in different zones of the kidney. In the present
      study, we demonstrate the feasibility of such a method on the basis of blood
      oxygenation level-dependent (BOLD) MRI, which allows sequential measurements in
      humans in response to a variety of physiological/ pharmacological stimuli in
      health and disease. METHODS AND RESULTS: BOLD MRI measurements were obtained in
      healthy young human subjects (n = 7), and the effects of three different
      pharmacological/physiological maneuvers that induce diuresis were studied. Spin
      spin relaxation rate, R2*, was measured, which is directly related to the amount
      of deoxyhemoglobin in blood and in turn to tissue PO2. Furosemide but not
      acetazolamide (n = 6 each) increased medullary oxygenation (delta R2* = 7.62 Hz;
      P < .01), consistent with the separate sites of action of these diuretics in the
      nephron and with previous direct measurements of their effects in anesthetized
      rats with oxygen microelectrodes. A new finding is that water diuresis improves
      medullary oxygenation (delta R2* = 6.43 Hz; P < .01) in young human subjects (n =
      5). CONCLUSIONS: BOLD MRI can be used to monitor changes in intrarenal
      oxygenation in humans in a noninvasive fashion.

PMID- 8989142
TI  - Direct intramuscular gene transfer of naked DNA encoding vascular endothelial
      growth factor augments collateral development and tissue perfusion.
AB  - BACKGROUND: Striated muscle has been shown to be capable of taking up and
      expressing foreign genes transferred in the form of naked plasmid DNA, although
      typically with a low level of gene expression. In the case of genes that encode
      secreted proteins, however, low transfection efficiency may not preclude bio
      activity of the secreted gene product. Accordingly, we investigated the
      hypothesis that intramuscular (IM) gene therapy with naked plasmid DNA encoding
      vascular endothelial growth factor (VEGF) could augment collateral development
      and tissue perfusion in an animal model of hindlimb ischemia. METHODS AND
      RESULTS: Ten days after ischemia was induced in one rabbit hindlimb, 500
      micrograms of phVEGF165, or the reporter gene LacZ, was injected IM into the
      ischemic hindlimb muscles. Thirty days later, angiographically recognizable
      collateral vessels and histologically identifiable capillaries were increased in
      VEGF transfectants compared with controls. This augmented vascularity improved
      perfusion to the ischemic limb, documented by a superior calf blood pressure
      ratio for phVEGF165 (0.85 +/- 0.05) versus controls (0.64 +/- 0.05, P < .01),
      improved blood flow in the ischemic limb (measured with an intra-arterial Doppler
      wire) at rest (phVEGF165 = 21.3 +/- 3.9 mL/min, control = 14.6 +/- 1.6 mL/min, P
      < .01) and after a vasodilator (phVEGF165 = 54.2 +/- 12.0 mL/min, control = 37.3
      +/- 8.9 mL/min, P < .01) and increased microspheres in the adductor (phVEGF165 =
      4.3 +/- 1.6 mL.min-1.100 g of tissue-1, control = 2.9 +/- 1.2 mL.min-1.100 g of
      tissue-1, P < .05) and gastrocnemius (phVEGF165 = 3.9 +/- 1.0 mL.min-1.100 g of
      tissue-1, control = 2.8 +/- 1.4 mL.min-1.100 g of tissue-1, P < .05) muscles of
      the ischemic limb. CONCLUSIONS: Ischemic skeletal muscle represents a promising
      target for gene therapy with naked plasmid DNA. IM transfection of genes encoding
      angiogenic cytokines, particularly those that are naturally secreted by intact
      cells, may constitute an alternative treatment strategy for patients with
      extensive peripheral vascular disease in whom the use of intravascular catheter
      based gene transfer is compromised and/or prohibited.

PMID- 8989143
TI  - Accelerated restitution of endothelial integrity and endothelium-dependent
      function after phVEGF165 gene transfer.
AB  - BACKGROUND: Delinquent reendothelialization (rET) has been shown to have a
      permissive, if not facilitatory, impact on smooth muscle cell proliferation. This
      inverse relation has been attributed to certain functions of the endothelium,
      including barrier regulation of permeability, thrombogenicity, and leukocyte
      adherence, as well as production of growth-inhibitory molecules. Accordingly, the
      present investigation was designed to test the hypothesis that an endothelial
      cell (EC) mitogen could serve as the basis for a novel gene therapy strategy
      designed to facilitate EC regeneration, reduce neointimal thickening, and promote
      recovery of EC dysfunction after balloon injury. METHODS AND RESULTS: New Zealand
      White rabbits underwent simultaneous balloon injury and gene transfer of one
      femoral artery with phVEGF165, encoding the 165-amino acid isoform of vascular
      endothelial growth factor (VEGF), or pGSVLacZ. In each animal transfected with
      phVEGF165 or pGSVLacZ, the contralateral femoral artery was also subjected to
      balloon injury but not to gene transfer. For pGSVLacZ, rET remained incomplete at
      4 weeks after transfection; in contrast, phVEGF165 produced prompt rET, which was
      95% complete by 1 week. Furthermore, rET in the contralateral, balloon-injured,
      nontransfected limb of the VEGF group was similarly accelerated. Consequently,
      intimal thickening was diminished, thrombotic occlusion was less frequent, and
      recovery of EC-dependent vasomotor reactivity was accelerated in VEGF
      transfectants compared with control animals. A similar benefit was observed for
      the contralateral, balloon-injured, nontransfected limb. CONCLUSIONS: Catheter
      mediated, site-specific arterial gene transfer of phVEGF165 can accelerate rET at
      local and remote sites, leading to inhibition of neointimal thickening, reduction
      in thrombogenicity, and restoration of endothelium-dependent vasomotor
      reactivity. These findings support the notion that gene transfer encoding for an
      EC-specific mitogen may be useful for preventing the complications, including
      restenosis, of balloon angioplasty.

PMID- 8989144
TI  - Chronic hypoxia increases beta 1-adrenergic receptor mRNA and density but not
      signaling in neonatal rat cardiac myocytes.
AB  - BACKGROUND: It is well recognized that the beta-adrenergic receptor
      adenylylcyclase system is altered during myocardial ischemia/hypoxia. However,
      there are no data regarding either regulation of beta-adrenergic receptors,
      particularly at the mRNA level, or adenylylcyclase activity in isolated cardiac
      myocytes exposed to chronic hypoxia. METHODS AND RESULTS: In a chronic hypoxia
      model in which neonatal rat ventricular myocytes were exposed to a 1% O2
      environment for 72 hours, we investigated (1) beta 1-mRNA and receptor expression
      and adenylylcyclase activity and (2) beta 1-mRNA and receptor downregulation and
      adenylylcyclase desensitization induced by prolonged norepinephrine incubation.
      We found that hypoxia for 72 hours increased myocardial membrane beta 1
      adrenergic receptor density by 44%. This increase was not associated with a
      corresponding decrease in cytosolic beta 1-adrenergic receptors. RNase protection
      assays demonstrated that hypoxia increased the steady-state levels of beta 1-mRNA
      by 109%. Adenylylcyclase activity stimulated by isoproterenol, sodium fluoride,
      guanyl-5'-imidodiphosphate, and forskolin in hypoxic membranes was not altered
      compared with normoxic controls. Hypoxia for 72 hours also did not affect
      norepinephrine-induced beta 1-mRNA and receptor downregulation and
      adenylylcyclase desensitization in response to isoproterenol, guanyl-5'
      imidodiphosphate, or forskolin. CONCLUSIONS: In neonatal rat cardiac myocytes,
      chronic hypoxia (1) increases beta 1-mRNA and receptor expression but does not
      alter adenylylcyclase activity stimulated at either the receptor or the
      postreceptor level and (2) does not affect agonist-induced beta 1-mRNA and
      receptor downregulation and desensitization of the adenylylcyclase response.

PMID- 8989145
TI  - Antithrombotic potential of polymer-coated stents eluting platelet glycoprotein
      IIb/IIIa receptor antibody.
AB  - BACKGROUND: Monoclonal anti-rabbit platelet glycoprotein (GP) IIb/IIIa antibody
      (AZ1) was adsorbed onto cellulose polymer-coated intracoronary stents to enhance
      their thromboresistance. We evaluated the antithrombotic efficacy of AZ1 antibody
      eluting stents. METHODS AND RESULTS: Twenty-three polymer-coated stents with AZ1
      antibody bound by passive adsorption (AZ1-eluting) were compared with 23 control
      polymer-coated stents adsorbed with either no antibody (base-polymer, n = 12) or
      isotype-matched irrelevant antibody (anti-CMV-eluting, n = 11) by implantation
      into balloon-damaged, flow-reduced iliac arteries of New Zealand White rabbits.
      In 13 animals (acute group), flow measurements were made with transit-time flow
      probes and platelet adhesion was ascertained by use of 111In-labeled autologous
      platelets. In the other 10 animals (chronic group), stent occlusion was assessed
      macroscopically after they were killed 28 days after stenting. Arteries with AZ1
      eluting stents had significantly less platelet deposition (15.8 +/- 4.5 x 10(7))
      than either base-polymer (32.1 +/- 4.3 x 10(7)) or anti-CMV-eluting (35.2 +/- 8.8
      x 10(7)) controls (ANOVA, P < .0001). Compared with base-polymer or anti-CMV
      eluting controls, arteries with AZ1-eluting stents showed a marked reduction in
      cyclic blood flow variation (P < .0001) and a significantly greater mean blood
      flow 2 hours after stent deployment (P < .0001). There was a significant
      improvement in the patency rate of AZ1-eluting stents compared with controls at
      both 2 hours (92% versus 46%, P = .034) and 28 days (100% versus 40%, P = .015).
      CONCLUSIONS: Platelet GP IIb/IIIa antibody eluting from polymer-coated stents
      reduces platelet deposition, improves blood flow, virtually abolishes cyclic flow
      variation, and improves patency rates after stent implantation in a rabbit iliac
      artery model. Its potential for reducing stent-related thrombosis in humans
      warrants further evaluation.

PMID- 8989146
TI  - Myocardial Gd-DTPA kinetics determine MRI contrast enhancement and reflect the
      extent and severity of myocardial injury after acute reperfused infarction.
AB  - BACKGROUND: Contrast medium-enhanced magnetic resonance images of acute,
      reperfused infarcts have shown hypoenhanced and hyperenhanced regions in areas of
      injured myocardium. The precise mechanisms that lead to these altered enhancement
      patterns are unknown. This study was designed to evaluate possible mechanisms and
      to relate altered enhancement patterns to myocardial perfusion and viability.
      METHODS AND RESULTS: Thirteen rabbits underwent in situ coronary artery occlusion
      and reperfusion followed by isolated perfusion with cardioplegic solution. T1
      weighted spin-echo images were acquired continuously during step changes in
      perfusate Gd-DTPA concentration. Regional blood flow was also measured by use of
      radioactive microspheres in all rabbits. There were marked differences in Gd-DTPA
      wash-in and washout time constants (wash-in, 0.8 +/- 0.1, 2.1 +/- 02, and 16.3 +/
      2.4 minutes, P < .001; washout, 1.6 +/- 0.1, 4.8 +/- 0.5, and 31.1 +/- 3.3
      minutes, P < .001) in normal, infarct rim, and infarct core regions,
      respectively, resulting in differential enhancement of these regions. Microsphere
      flows in the infarct rim and core were 42.9 +/- 4.0% and 12.0 +/- 1.6% of normal
      myocardium and correlated well with washout time constants (r = .86, y = 0.77x -
      0.002, P < .001), suggesting that these time constants index the severity of
      microvascular damage. In addition, spatial maps of washout time constants were
      produced. The extent of regions with abnormal time constants correlated well with
      triphenyltetrazolium chloride-determined infarct size (r = .94, y = 0.95x + 4.17,
      P < .001). CONCLUSIONS: In contrast-enhanced magnetic resonance images of acute,
      reperfused rabbit infarcts, differential image intensity is primarily due to
      regional differences in contrast agent wash-in and washout time constants. These
      regional differences in time constants also indicate the extent and severity of
      myocardial injury.

PMID- 8989147
TI  - Antibody to platelet/endothelial cell adhesion molecule-1 reduces myocardial
      infarct size in a rat model of ischemia-reperfusion injury.
AB  - BACKGROUND: Antibodies to selected neutrophil or endothelial cell adhesion
      molecules decrease myocardial infarct size in vivo. Platelet/endothelial cell
      adhesion molecule-1 (PECAM-1) is an immunoglobulin gene superfamily member
      expressed constitutively on neutrophils and endothelium. F(ab')2 fragments of
      antibody against PECAM-1 inhibit transendothelial migration of neutrophils in
      several in vivo models of acute inflammation. Therefore, we examined the effect
      of F(ab')2 fragments of anti-PECAM-1 antibody in a rat model of myocardial
      infarction. METHODS AND RESULTS: F(ab')2 fragments of the anti-PECAM-1 antibody
      SEW16 and control normal rabbit IgG (NRIgG) were administered at 5 mg/kg to male
      Wistar rats, and the rats were subjected to a 30-minute coronary artery occlusion
      followed by 2 hours of reperfusion. At the completion of each experiment, the
      area at risk, infarct size (IS), and myeloperoxidase (MPO) activity were
      determined. Compared with untreated (n = 8; IS, 57 +/- 5%) or NRIgG-treated (n =
      10; IS, 62 +/- 3%) control rats, SEW16-treated rats (n = 15; IS, 28.5 +/- 4%)
      displayed a 54% decrease in myocardial infarct size (P < .001). Hemodynamic
      parameters, leukocyte counts, total left ventricular weight, and area-at-risk
      weights did not differ significantly between the treatment groups. However,
      measurement of MPO activity revealed that neutrophil accumulation was reduced 83%
      (NRIgG, 975 +/- 55 mU/g; SEW16, 167 +/- 62 mU/g). CONCLUSIONS: These results
      demonstrate that blocking PECAM-1 exerts a significant protective effect in a rat
      model of myocardial ischemia-reperfusion injury via blockade of neutrophil
      accumulation in the myocardium.

PMID- 8989148
TI  - A novel site-targeted ultrasonic contrast agent with broad biomedical
      application.
AB  - BACKGROUND: In this work, we report a novel targetable ultrasonic contrast agent
      with the potential to noninvasively define and localize myriad pathological
      tissues for diagnosis or therapy. The agent is a biotinylated, lipid-coated,
      perfluorocarbon emulsion that has low inherent echogenicity unless bound to a
      surface or itself. METHODS AND RESULTS: In study 1, emulsions with and without
      biotin were suspended in buffered saline and imaged with a 7.5-MHz linear-array
      transducer. Neither emulsion manifested significant ultrasonic backscatter until
      avidin was added. Avidin-induced aggregation produced a marked enhancement in
      backscatter from the biotinylated but not from the control emulsion. In study 2,
      porcine fibrin clots in vitro were pretargeted with biotinylated antifibrin
      monoclonal antibodies and then exposed to avidin and then to biotinylated or
      control perfluorocarbon emulsions. The basal acoustic reflectivity of clots
      imaged with a 7.5-MHz linear-array transducer was uniformly low and was increased
      substantially by exposure to the targeted biotinylated emulsion. In study 3,
      partially occlusive arterial thrombi were created in dogs and then exposed to
      antifibrin antibodies and avidin in situ. Biotinylated or control emulsion was
      administered either in situ or systemically. At baseline, all thrombi were
      undetectable with a 7.5-MHz linear-array transducer. Thrombi exposed to
      antifibrin-targeted contrast exhibited increased echogenicity (P < .05); control
      thrombi remained acoustically undetectable. CONCLUSIONS: These data provide the
      first in vivo demonstration of a site-specific ultrasonic contrast agent and have
      potential for improved sensitivity and specificity for noninvasive diagnosis of
      thrombi and other pathological diseases.

PMID- 8989150
TI  - Autoimmune response in chronic ongoing myocarditis demonstrated by heterotopic
      cardiac transplantation in mice.
AB  - BACKGROUND: Autoimmune mechanisms have been implicated in the pathogenesis of
      chronic ongoing myocarditis. To investigate this relation, we used an A/J mouse
      model inoculated with coxsackievirus B3 and determined whether myocarditis would
      be transferred to normal hearts that were heterotopically transplanted. METHODS
      AND RESULTS: Inbred 3-week-old A/J mice were inoculated intraperitoneally with
      coxsackievirus B3 (Nancy strain; 2 x 10(4) plaque-forming units) and housed for >
      60 days. The presence of the viral genome in the myocardium was determined by the
      polymerase chain reaction with primers specific for the 5' end of the
      coxsackievirus B3 genome performed at 40, 50, or 60 days after inoculation.
      Normal A/J mouse hearts were transplanted into the same strain of mice without
      myocarditis (group A) and into mice with chronic ongoing myocarditis (group B).
      The hearts were evaluated histologically 2 weeks after transplantation.
      Conventional histological examination of infiltrated T cells and macrophages was
      performed, and the expression of intercellular adhesion molecule-1, major
      histocompatibility complex (MHC) class I antigen, and MHC class II antigen was
      evaluated by immunoenzymatic staining. The concentrations of interleukin-1 alpha
      (IL-1 alpha) and tumor necrosis factor (TNF-alpha) in the grafts were measured
      with an ELISA. The viral RNA genomes were not detected in the mice with chronic
      ongoing myocarditis, but their transplanted hearts did show myocarditis. In the
      hearts with induced myocarditis, infiltrated mononuclear cells consisted of CD4+
      T cells, CD8+ T cells (CD4+ cell number > CD8+ cell number), and macrophages.
      Intercellular adhesion molecule-1, MHC class I antigen, and MHC class II antigen
      were expressed in the vascular endothelial cells and myocardial cells in and
      around the infiltrated lesions. The concentrations of IL-1 alpha and TNF-alpha in
      group B were significantly higher than those in group A (group A versus group B:
      IL-1 alpha, 125 +/- 35 versus 180 +/- 34 pg/mL; TNF-alpha, 45 +/- 15 versus 96 +/
      40 pg/mL; P < .05). CONCLUSIONS: Results suggest that an autoimmune response may
      play a key role in the progression of chronic ongoing myocarditis.

PMID- 8989149
TI  - Nitric oxide attenuates the release of endothelium-derived hyperpolarizing
      factor.
AB  - BACKGROUND: The contribution of the endothelium-derived hyperpolarizing factor
      (EDHF), proposed to be a cytochrome P450-derived metabolite of arachidonic acid,
      to endothelium-dependent dilatation under physiological conditions has yet to be
      established, because its effect can be detected only after inhibition of NO
      synthase and cyclooxygenase. The possibility that NO exerts a feedback inhibition
      on EDHF formation was studied in isolated perfused arterial segments. METHODS AND
      RESULTS: Under combined blockade of NO synthase and cyclooxygenase, the EDHF
      mediated vasodilatation elicited by receptor-dependent agonists in rabbit carotid
      and porcine coronary arteries was significantly attenuated by the NO donors C87
      3786 and CAS 1609. The endothelium-independent dilatation elicited by
      isoproterenol was not altered by either NO donor. In NG-nitro-L-arginine-treated
      carotid artery segments, C87-3786 significantly attenuated the acetylcholine
      induced increase in 6-keto-prostaglandin F1 alpha release, which was taken as an
      index of arachidonic acid liberation. In parallel experiments using cultured
      human endothelial cells, C87-3786 attenuated the Ca2+ response to bradykinin. The
      release of EDHF from a luminally perfused porcine coronary artery was detected by
      recording the membrane potential of downstream-situated cultured rat aortic
      smooth muscle cells. The NO donor C87-3786 had no effect on the hyperpolarization
      elicited by preformed EDHF but markedly inhibited its release from bradykinin
      stimulated donor segments. CONCLUSIONS: These findings indicate that under
      physiological conditions, the production of EDHF is damped by NO. Therefore, it
      follows that when NO synthesis is impaired, alleviation of this intrinsic
      inhibition may, at least in part, maintain endothelial vasodilator function.

PMID- 8989151
TI  - Inhibition of transplant coronary arteriosclerosis in rabbits by chronic
      estradiol treatment is associated with abolition of MHC class II antigen
      expression.
AB  - BACKGROUND: Accelerated coronary arteriosclerosis is a major complication in long
      term survivors of cardiac transplantation. Estrogen prevents transplant
      arteriosclerosis in experimental cardiac and aortic allografts and may act by an
      immune mechanism. METHODS AND RESULTS: New Zealand White rabbits immunosuppressed
      with cyclosporine were recipients of cardiac allografts from Dutch Belted
      rabbits. The recipients received either estradiol or placebo daily until they
      were killed 6 weeks later. Histological cross sections of the cardiac allograft
      were used for quantification of major histocompatibility complex (MHC) class II
      antigen expression, T lymphocytes, and macrophages by immunohistochemistry using
      monoclonal antibodies. MHC class II antigen expression was not detectable in
      allograft coronary arteries from any of the estradiol-treated recipients, whereas
      this antigen expression was present in the allograft coronary arteries from all
      the placebo-treated recipients. Macrophage and lymphocyte infiltration of the
      allograft coronary artery myointima was significantly less frequent in the
      estradiol-treated group. Rejection was moderate but slightly less in the
      estradiol-treated group. These findings were associated with a 60% decrease in
      allograft coronary artery myointimal thickening (determined by morphometry) in
      the estradiol-treated compared with the placebo-treated group. CONCLUSIONS:
      Estradiol treatment of cardiac allograft recipients abolishes MHC class II
      antigen expression in the coronary arteries and decreases macrophage infiltration
      in all three layers of the vessel wall, whereas T-lymphocyte infiltration is
      decreased only in the myointima. These findings are associated with estradiol
      inhibition of myointimal proliferation. Thus, estradiol treatment may have a
      beneficial effect on graft arteriosclerosis through immune mechanisms.

PMID- 8989153
TI  - The myth of the myocardial 'infarctlet' during percutaneous coronary
      revascularization procedures.

PMID- 8989152
TI  - Influence of aortic impedance on the development of pressure-overload left
      ventricular hypertrophy in rats.
AB  - BACKGROUND: Aortic input impedance, which represents LV afterload, is considered
      to be a major determinant for the development of pressure-overload left
      ventricular (LV) hypertrophy. METHODS AND RESULTS: To test whether the sustained
      change in aortic input impedance might affect the mode of development of LV
      hypertrophy, coarctation of either the ascending aorta (G1, n = 13) or suprarenal
      abdominal aorta (G2, n = 12) was performed over 4 weeks in 6-weeks-old Wistar
      rats. Although peak LV pressure and total systemic resistance were increased
      similarly in G1 and G2, time to peak LV pressure was decreased by 24% (P < .01)
      in G1 compared with G2. The aortic input impedance spectra revealed that the
      early systolic loading in G1 was characterized by an increase in characteristic
      impedance, whereas the late systolic loading in G2 was by an augmented arterial
      wave reflection. G1 showed a smaller increase (P < .01) in either the ratio of LV
      weight (mg) to body weight (g) or LV wall thickness than G2 after aortic banding.
      Myocyte diameter was also smaller (P < .05) in G1 (14.3 +/- 0.7 mm) than in G2
      (16.1 +/- 1.2 mm). The ex vivo passive pressure-volume relation had a rightward
      shift in G1 compared with G2, suggesting less concentric LV hypertrophy in G1.
      CONCLUSIONS: The sustained early systolic loading due to the increase in
      characteristic impedance was accompanied by less concentric, reduced hypertrophy,
      whereas the sustained late systolic loading due to the augmented arterial wave
      reflection was accompanied by concentric, adequate hypertrophy.

PMID- 8989154
TI  - Angina pectoris and progressive fatigue in a 61-year-old man.

PMID- 8989155
TI  - Images in cardiovascular medicine. Plaque types.

PMID- 8989156
TI  - Understanding obesity in youth. A statement for healthcare professionals from the
      Committee on Atherosclerosis and Hypertension in the Young of the Council on
      Cardiovascular Disease in the Young and the Nutrition Committee, American Heart
      Association. Writing Group.

PMID- 8989157
TI  - A 30-year perspective on alpha 1-antitrypsin deficiency.
AB  - The early history of alpha 1-antitrypsin deficiency, in the years between 1962
      and 1965, and its impact on the understanding of emphysema abnormalities were
      reviewed by me in 1989. This report discusses the disease spectrum (including
      emphysema, liver, and vasculitic diseases) and focuses on the variable clinical
      expression of the deficiency state. Some new findings that may be relevant to the
      function of alpha 1-antitrypsin are also considered.

PMID- 8989158
TI  - Alpha 1-antitrypsin deficiency. A conformational disease.
AB  - The serpin family of protease inhibitors, to which alpha 1-antitrypsin belongs,
      has the unique feature of a mobile reactive center. Mutations within the critical
      regions of the molecule that control this mobility can allow premature changes in
      conformation with consequent abnormalities in folding and accompanying polymer
      formation. These abnormalities explain the plasma deficiency and liver inclusions
      associated with the common Z variant, as well as other variants of alpha 1
      antitrypsin. The understanding of the molecular mechanisms provides a satisfying
      explanation for the clinical findings associated with these deficiency variants.

PMID- 8989159
TI  - Pathogenesis of hereditary emphysema and replacement therapy for alpha 1
      antitrypsin deficiency. Insight into the more common forms of emphysema.

PMID- 8989160
TI  - Pathogenesis and pathology of liver disease associated with alpha 1-antitrypsin
      deficiency.
AB  - alpha 1-Antitrypsin (alpha 1-AT) accumulates in the rough endoplasmic reticulum
      through a mechanism of polymerization. Polymerization is favored by the incorrect
      tertiary structure of the alpha 1-AT caused by a point mutation at position 342
      of the protein. Accumulation of alpha 1-AT in the liver cells (and in hepatocytes
      and colangiocytes) is not sufficient per se to explain the liver disease that is
      manifested in a minority of PiZ subjects and thus, a trigger factor must be
      hypothesized. A virus (hepatitis C virus or some other kind of virus not
      identified as yet) is among the most probable trigger factors. In Z subjects
      (among the general population), relevant liver disease is probably a more rare
      event than thought in the past and most of these subjects escape major liver
      disease. Usually, liver disease is not a significant problem in patients with
      COPD.

PMID- 8989161
TI  - Opportunities for the use of aerosolized alpha 1-antitrypsin for the treatment of
      cystic fibrosis.
AB  - Cystic fibrosis (CF), the most common lethal genetic disease affecting the white
      population, owes its morbidity and mortality primarily to the devastating effects
      of chronic inflammation and infection within the pulmonary airways. It has become
      increasingly recognized that the host's response to Pseudomonas species and
      Staphylococcus aureus infection plays a paramount role in CF lung destruction and
      eventual development of respiratory insufficiency. A massive pulmonary influx of
      neutrophils, and accompanying excessive levels of neutrophil elastase (NE), can
      be detected in the bronchoalveolar fluid of even very young children with CF. The
      excess of NE adversely affects the CF airways by enhancing mucus secretion,
      directly injuring airway tissues, exacerbating the inflammatory process by
      attracting more neutrophils, and derailing opsonization and elimination of
      bacterial pathogens, particularly Pseudomonas aeruginosa. Neutralization of
      excess NE by delivering supplemental alpha 1-antitrypsin to the airways via
      aerosolization represents an exciting new potential therapy for CF lung disease.

PMID- 8989162
TI  - Use of secretory leukoprotease inhibitor to augment lung antineutrophil elastase
      activity.
AB  - Physiologically, secretory leukoprotease inhibitor (SLPI) is the major
      antiprotease of the epithelium of the upper respiratory tract providing
      protection against neutrophil elastase (NE). The recombinant form of SLPI (rSLPI)
      has several advantages compared with alpha 1-antitrypsin that make it interesting
      as potential therapy. In vitro, rSLPI proves to be an excellent inhibitor of NE.
      When administered as an aerosol in vitro and in vivo, the structure and function
      of rSLPI remain intact. Using the aerosol route, the half-life of rSLPI in
      respiratory epithelial lining fluid is 12 h; thus, giving it twice daily should
      guarantee satisfactory levels in the lung. Following inhalation, rSLPI moves from
      the epithelium in an intact form into the interstitium of the lung. Following on
      from these in vitro and in vivo experiments, a short-term study in patients with
      cystic fibrosis was performed with aerosolized rSLPI. Promising results relative
      to NE level reduction and the consequences for the inflammatory process in the
      bronchi were achieved. rSLPI not only induced an increase of the anti-NE
      protective screen, but also improved the antioxidant protection by raising
      glutathione levels in the lung in sheep. rSLPI may therefore provide a unique
      opportunity for protecting the lung from the damage caused by inflammatory
      processes by giving a single drug.

PMID- 8989163
TI  - Oxidant-protease interaction in the lung. Prospects for antioxidant therapy.
AB  - In inflammatory lung disorders, oxidants and proteases complement each other in
      their potential to destroy lung parenchyma. It is therefore rational to combine
      therapeutic strategies aimed at augmenting the antiproteolytic defenses of the
      lung in diseases such as emphysema with antioxidant strategies. In the healthy
      lung, the oxidant burden is balanced by the local antioxidant defenses. However,
      both an increased oxidant burden and/or decreased antioxidant defenses may
      reverse the physiologic oxidant-antioxidant balance in favor of oxidants, leading
      to lung injury. This concept points to an obvious therapeutic strategy:
      augmentation of the antioxidant screen of the lung to prevent oxidant-mediated
      tissue damage. Studies using reduced glutathione (GSH), the major pulmonary
      antioxidant, as a model therapeutic agent demonstrated that GSH can be
      administered directly to the respiratory epithelial surface by aerosol and is
      fully functional as an antioxidant both in vitro and in vivo. In pulmonary
      diseases such as idiopathic pulmonary fibrosis or following HIV infection, GSH
      aerosol therapy not only normalized deficient pretherapy GSH levels in the lung,
      but was capable of favorably influencing cellular events such as oxidant release
      by pulmonary inflammatory cells. The same was true for oral antioxidant therapy
      with N-acetylcysteine, a glutathione precursor. These results suggest that it is
      possible to use antioxidants to reverse the imbalance between oxidants and
      antioxidants at the site of oxidant injury to prevent the progressive tissue
      damage in lung disorders characterized by high oxidant states. Antioxidants,
      alone and in combination with antiproteases, merit further long-term studies for
      clinical therapy.

PMID- 8989164
TI  - The interdependence of lung antioxidants and antiprotease defense in ARDS.
AB  - As in hereditary alpha 1-antitrypsin deficiency, protease-antiprotease and
      oxidant-antioxidant balances play a significant role in the pathogenesis of ARDS.
      However, the disease processes and possibilities for therapeutic intervention
      differ markedly.

PMID- 8989165
TI  - Bioengineering: alpha 1-proteinase inhibitor site-specific mutagenesis. The
      prospect for improving the inhibitor.
AB  - alpha 1-Proteinase inhibitor (alpha 1-PI) augmentation therapy has been licensed
      for treatment of alpha 1-PI-deficient individuals with pulmonary emphysema. The
      currently available product is purified from pooled human plasma. To obtain
      larger amounts of protein free from possible unknown plasma contaminants, human
      alpha 1-PI has been produced by recombinant DNA. Since wild-type alpha 1-PI is
      susceptible to oxidative impairment, several alpha 1-PI variants in which the
      active site oxidation-sensitive residue is replaced by inert residues have been
      constructed. This article is aimed at reviewing the history, biological efficacy,
      advantages, disadvantages, and concerns linked to alpha 1-PI recombinant DNA and
      site-specific mutagenesis technology.

PMID- 8989166
TI  - Lung transplantation for alpha 1-antitrypsin deficiency emphysema.
AB  - Lung transplantation is an option for appropriately selected patients with end
      stage emphysema caused by alpha 1-antitrypsin deficiency. The functional results
      have been excellent after single or bilateral lung transplantation, and the
      medium-term survival results have been good. However, the role of alpha 1
      antitrypsin replacement therapy after lung transplantation remains uncertain, and
      further investigation is needed.

PMID- 8989167
TI  - Assessing quality of life following cardiac surgery: an elusive goal.

PMID- 8989168
TI  - Continuous venovenous hemofiltration with dialysis and lactate clearance in
      critically ill patients.

PMID- 8989169
TI  - Indices of hypoxemia in patients with acute respiratory distress syndrome:
      reliability, validity, and clinical usefulness.

PMID- 8989170
TI  - Prediction of outcome from intensive care: a prospective cohort study comparing
      Acute Physiology and Chronic Health Evaluation II and III prognostic systems in a
      United Kingdom intensive care unit.
AB  - OBJECTIVE: To evaluate the ability of two prognostic systems to predict hospital
      mortality in adult intensive care patients. DESIGN: Prospective cohort study.
      SETTING: A mixed medical and surgical intensive care unit (ICU) in the United
      Kingdom. PATIENTS: A total of 1,144 patients consecutively admitted to the study.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute Physiology and Chronic
      Health Evaluation (APACHE) II and III prognostic systems were applied to assess
      probabilities of hospital mortality, which were compared with the actual outcome.
      The overall goodness-of-fit of both models was assessed. Hospital death rates
      were higher than those predicted by each system. Risk estimates showed a strong
      positive correlation between both systems (nonsurvivors r2 = 0.756, p < .0001;
      survivors r2 = 0.787, p < .0001). Calibration of APACHE II (chi 2 = 98.6,
      Lemeshow-Hosmer) was superior to that of APACHE III (chi 2 = 129.8, Lemeshow
      Hosmer). The total correct classification rate of APACHE III was greater for all
      decision criteria applied; the best overall total correct classification rate was
      80.6% for APACHE III and 77.9% for APACHE II (both for a decision criterion of
      40%). The areas under the receiver operating characteristic curves were 0.806 and
      0.847 for APACHE II and III, respectively, confirming the better discrimination
      of APACHE III. When patients were classified by diagnostic categories, risk
      predictions did not fit uniformly across the spectrum of disease groups. For both
      models, mortality ratios were highest for trauma patients and lowest for the
      group with respiratory disease. APACHE II predictions for patients with
      gastrointestinal disease were significantly better. Risk estimates for surgical
      admissions were superior with APACHE II (MR = 1.27) compared with APACHE III (MR
      = 1.56), but were similar for medical patients (1.22 vs. 1.28 for APACHE II and
      III, respectively). Bias induced by factors reflecting the clinical practice in
      an individual ICU (e.g., admission criteria, treatment before admission) may have
      considerable impact on risk estimates. The identification of such factors appears
      to be a prerequisite for the meaningful interpretation of observed and predicted
      death rates on the individual ICU level. CONCLUSIONS: Both predictive models
      demonstrated a similar degree of overall goodness-of-fit. APACHE II showed better
      calibration, but discrimination was better with APACHE III. Hospital mortality
      was higher than predicted by both models, but was underestimated to a greater
      degree by APACHE III. Risk estimates by both models showed considerable variation
      across the disease spectrum of ICU patients. Risk predictions for surgical
      patients and patients with gastrointestinal disease were better with APACHE II.
      Factors reflecting the clinical practice of an individual ICU are not accounted
      for by APACHE II and III. Overall, the performance of APACHE III was not superior
      to that of its predecessor for a cohort of United Kingdom ICU patients; for
      certain diagnostic categories, APACHE III performed worse than APACHE II despite
      an improved system of disease classification.

PMID- 8989171
TI  - Influence of prone position on the extent and distribution of lung injury in a
      high tidal volume oleic acid model of acute respiratory distress syndrome.
AB  - OBJECTIVE: To evaluate the influence of body position on the extent and
      distribution of experimental lung damage in an oleic acid canine model of acute
      respiratory distress syndrome, using mechanical ventilation with high tidal
      volumes and positive end-expiratory pressure (PEEP). DESIGN: Prospective,
      randomized study. SETTING: Experimental animal laboratory. SUBJECTS: Twelve
      anesthetized and paralyzed dogs. INTERVENTIONS: Ninety minutes after lung injury
      was induced by injection of oleic acid, 12 animals were randomized to be
      ventilated for 4 hrs, in either the supine (supine group, n = 6) or prone (prone
      group, n = 6) positions, using the same ventilatory pattern (F10(2) 0.6, PEEP >
      or = 10 cm H2O, and a tidal volume that generated a peak transpulmonary pressure
      of 35 cm H2O when implemented in the supine position). Regardless of
      randomization to position, the tidal volumes, F10(2), and PEEP were kept constant
      and the pulmonary artery occlusion pressure was maintained between 4 and 6 mm Hg
      for the duration of the study. MEASUREMENTS AND MAIN RESULTS: At the end of the
      protocol, the lungs were excised for gravimetric determination (wet/dry weight
      ratio) and histologic examination (histologic score). Changes over time in the
      static pressure-volume curve of the lungs (obtained in the supine position) were
      also used as end-point variables. At baseline, hemodynamic and respiratory
      variables did not differ between groups. Just before randomization to position
      (90 mins after oleic acid injection), both groups presented similar lung static
      pressure-volume curves. Pulmonary artery occlusion pressure (4.3 +/- 1.9 vs. 4.8
      +/- 1.3 mm Hg [supine vs. prone group]), cardiac output (4.1 +/- 0.4 vs. 5.2 +/-
      1.3 L/min [supine vs. prone group]), and venous admixture (36.7 +/- 20.7% vs.
      28.3 +/- 19.4% [supine vs. prone group]) were also not significantly (p > .05)
      different when measured in the supine position. At the end of the experiment,
      lung gravimetric data in the two experimental groups were not statistically
      different, suggesting a similar extent of edema. Histologic abnormalities,
      however, were less in the prone group than in the supine group (p < .01), due
      primarily to marked differences in extent and severity in the dependent regions
      of the lungs. Static lung compliance improved over time in the prone group (34 +/
      9 to 46 +/- 19 mL/cm H2O)(p = .02), but not in the supine group (34 +/- 6 to 36
      +/- 6 mL/cm H2O). CONCLUSIONS: After oleic acid-induced lung injury, animals
      ventilated with high tidal volume and PEEP undergo less extensive histologic
      change in the prone position than in the supine position. The prone position
      alters the distribution of histologic abnormalities.

PMID- 8989172
TI  - Mortality is directly related to the duration of mechanical ventilation before
      the initiation of extracorporeal life support for severe respiratory failure.
AB  - OBJECTIVE: To investigate the relationship between the period of mechanical
      ventilation before extracorporeal life support and survival in patients with
      respiratory failure. DESIGN: Retrospective review. SETTING: Surgical intensive
      care unit at a university medical center. PATIENTS: Thirty-six consecutive adult
      patients with severe respiratory failure managed with extracorporeal life
      support. INTERVENTIONS: Extracorporeal life support was utilized in 36 acute
      respiratory failure adult patients with a variety of diagnoses and an estimated
      mortality rate of > 90%. Management protocols were followed before and during
      extracorporeal life support. The 36 patients were physiologically similar before
      extracorporeal life support was initiated: shunt of 48 +/- 17%; F10(2) of 1.0 +/-
      0.1; peak inspiratory pressure of 56 +/- 16 cm H2O; positive end-expiratory
      pressure of 14 +/- 6 cm H2O; and respiratory rate of 23 +/- 10 breaths/ min.
      Ventilation was utilized for 1 to 17 days before extracorporeal life support.
      Typical lung rest settings during extracorporeal life support were F10(2) of
      0.40, peak inspiratory pressure of 30 cm H2O, positive end-expiratory pressure of
      10 cm H2O, and respiratory rate of 6 breaths/min. Death was almost always
      secondary to end-stage pulmonary failure. MEASUREMENTS AND MAIN RESULTS: Survival
      (hospital discharge) in these 36 patients was inversely associated with the
      number of days of preextracorporeal life support ventilation, with a 50%
      mortality rate predicted by logistic regression after 5 days of mechanical
      ventilation. The overall survival rate was 18 (50.0%) of 36 patients.
      CONCLUSIONS: In severe acute respiratory failure treated with lung rest and
      extracorporeal life support, a predicted 50% mortality rate was associated with 5
      days of preextracorporeal life support mechanical ventilation.

PMID- 8989173
TI  - Prolonged sedation of critically ill patients with midazolam or propofol: impact
      on weaning and costs.
AB  - OBJECTIVE: To compare the effectiveness of sedation, the time required for
      weaning, and the costs of prolonged sedation of critically ill mechanically
      ventilated patients with midazolam and propofol. DESIGN: Open-label, randomized,
      prospective, phase IV clinical trial. SETTING: Medical and surgical intensive
      care unit (ICU) in a community hospital. PATIENTS: All ICU admissions (medical,
      surgical and trauma) requiring mechanical ventilation for > 24 hrs. A total of
      108 patients were included in the study. INTERVENTIONS: Patients were randomized
      to receive midazolam or propofol. The dose range allowed for each drug was 0.1 to
      0.5 mg/kg/hr for midazolam and 1 to 6 mg/kg/hr for propofol. The lowest dose that
      achieved an adequate patient-ventilator synchrony was infused. All patients
      received 0.5 mg/kg/24 hrs of morphine chloride. MEASUREMENTS AND MAIN RESULTS:
      The level of sedation was quantified by the Ramsay scale every 2 hrs until
      weaning from mechanical ventilation was started. If sedation could not be
      achieved by infusing the highest dose of midazolam or propofol, the case was
      recorded as a therapeutic failure. In the propofol group, serum triglycerides
      were determined every 72 hrs. Concentrations of > 500 mg/dL were also recorded as
      a therapeutic failure. When the patient was ready for weaning according to
      defined criteria, sedation was interrupted abruptly and the time from
      interruption of sedation to the first T-bridge trial and to extubation was
      measured. Cost analysis was performed based on the cost of intensive care in our
      unit ($54/hr). In the midazolam group (n = 54), 15 (27.8%) patients died; 11
      (20.4%) patients had therapeutic failure; and 28 (51.8%) patients were subjected
      to a T-bridge trial. In the propofol group (n = 54), these proportions were 11
      (20.4%), 18 (33.4% [including seven due to inadequate sedation, and 11 due to
      hypertriglyceridemia]), and 25 (46.2%), respectively. None of these values was
      significantly different between the two groups. Duration of sedation was 141.7 +/
      89.4 (SD) hrs and 139.7 +/- 84.7 hrs (p = NS), and cost (US dollars) attributed
      to sedation was $378 +/- 342 and $1,047 +/- 794 (p = .0001) for the midazolam and
      propofol groups, respectively. In the midazolam group, time from discontinuation
      of the drug infusion to extubation was 97.9 +/- 54.6 hrs (48.9 +/- 47.2 hrs to
      the first disconnection, and 49.0 +/- 23.7 hrs to extubation). In the propofol
      group, time from discontinuation of the drug infusion to extubation was 34.8 +/-
      29.4 hrs (4.0 +/- 3.9 hrs to the first disconnection, and 30.8 +/- 29.2 hrs to
      extubation). The difference between the two groups in the weaning time was 63.1
      +/- 12.5 (SEM) hrs (p < .0001). Cost per patient in the midazolam group
      (including ICU therapy and sedation with midazolam) was $10,828 +/- 5,734. Cost
      per patient in the propofol group was $9,466 +/- 5,820, $1,362 less than in the
      midazolam group. CONCLUSIONS: In our population of critically ill patients
      sedated with midazolam or propofol over prolonged periods, midazolam and propofol
      were equally effective as sedative agents. However, despite remarkable
      differences in the cost of sedation with these two agents, the economic profile
      is more favorable for propofol than for midazolam due to a shorter weaning time
      associated with propofol administration.

PMID- 8989174
TI  - Variability of indices of hypoxemia in adult respiratory distress syndrome.
AB  - OBJECTIVE: To determine the usefulness of indices of hypoxemia in assessing
      patients with the adult respiratory distress syndrome (ARDS). DESIGN:
      Retrospective analysis of previously published data that describe the
      distributions of ventilation and pulmonary blood flow in ARDS. SETTING:
      University research laboratory. PATIENTS: Sixteen patients with ARDS.
      INTERVENTIONS: The FIO2 was varied between 0.21 and 1.0 in a computer model of
      gas exchange, based on a 50-compartment model of ventilation/perfusion
      inhomogeneity plus true shunt and deadspace. The indices of hypoxemia that were
      calculated as a function of inspired oxygen concentration included PaO2/FIO2,
      arterial/alveolar ratio (PaO2/alveolar PO2), the alveolar-arterial PO2 difference
      (P[A-a]O2), respiratory index (P[A-a]O2/PaO2), and venous admixture. MEASUREMENTS
      AND MAIN RESULTS: The PaO2/FIO2 ratio in patients with moderate shunts (< 30%)
      varied considerably with alteration in FIO2. At both extremes of FIO2, the
      PaO2/FIO2 in these patients was substantially greater than at intermediate FIO2.
      Patients with larger shunts (> 30%) had greater PaO2/FIO2 ratios at low FIO2, but
      the PaO2/FIO2 ratios decreased to relatively stable values at FIO2 values of >
      0.5. In all patients, PaO2/FIO2 remained relatively stable at FIO2 values of > or
      = 0.5 and PaO2 values of < or = 100 torr (< or = 13.3 kPa). Other PO2-based
      indices exhibited less stability as FIO2 was varied. If hypoxemia resulted from
      true shunting, venous admixture was found to be stable at all FIO2 values.
      However, approximately one half of patients had clinically important hypoxemia
      resulting from mismatching of ventilation and blood flow. In these patients,
      venous admixture varied substantially with change in FIO2, and the degree of
      variation was proportional to the fraction of cardiac output perfusing gas
      exchange units with ventilation/perfusion ratios of < 0.1. CONCLUSIONS: All
      indices of hypoxemia are affected by changes in FIO2 in patients with ARDS.
      PaO2/FIO2 ratio exhibits the most stability at FIO2 values of > or = 0.5 and PaO2
      values of < or = 100 torr (< or = 13.3 kPa), and is a useful estimation of the
      degree of gas exchange abnormality under usual clinical conditions. Venous
      admixture varies substantially with alteration of FIO2 in patients who have
      clinically important ventilation/perfusion abnormalities. Under these
      circumstances, venous admixture is a poor indicator of the efficiency of
      pulmonary oxygen exchange, even if venous admixture is calculated from measured
      arterial and venous oxygen content values. Estimated venous admixture, based on
      an assumed arterial-venous oxygen content difference, is even more unreliable.

PMID- 8989175
TI  - Type B lactic acidosis following cardiopulmonary bypass.
AB  - OBJECTIVE: To describe, characterize, and identify the associations of
      postcardiac surgical lactic acidosis occurring in the absence of clinical
      evidence of tissue hypoperfusion. DESIGN: The preliminary study is a report of a
      series of observations in 12 patients. The prospective study is also
      observational, involving the structured collection of hemodynamic and metabolic
      variables in a prescribed series of patients. SETTING: Cardiac surgical intensive
      care unit of a university teaching hospital. PATIENTS: Twelve patients who
      developed an unexplained lactic acidosis after cardiac surgery are reported in
      the preliminary study. The prospective study involved observations in 112
      consecutive patients undergoing cardiopulmonary bypass for cardiac surgery.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preliminary study: Cardiac
      index was increased before, during and after recovery from lactic acidosis.
      Recovery from lactic acidosis was associated with a decrease in oxygen transport
      index and significant increases in oxygen consumption index and oxygen extraction
      ratio. PROSPECTIVE STUDY: Hemodynamic, oxygen transport, and oxygen consumption
      variables, together with arterial blood gas and lactate concentrations, were
      assessed every 6 hrs for 24 hrs after surgery. Sixteen patients developed lactic
      acidosis (peak lactate concentration > 5.0 mmol/L). Compared with the remainder
      of the patients, this subgroup had longer duration of cardiopulmonary bypass (116
      +/- 31 vs. 76 +/- 31 mins, p < .01), greater intraoperative hypothermia (24.9 +/-
      2.0 degrees vs. 26.6 +/- 2.3 degrees C, p < .01), more frequent requirement for
      vasopressor agents (14/16 vs. 35/96, p < .05) and a higher frequency of
      hyperglycemia (15/16 vs. 28/96, p < .01). Hemodynamic variables, including
      cardiac index, were remarkably similar in the acidotic and nonacidotic groups.
      All of the acidotic patients, in both parts of this study, recovered from their
      acidosis. Eleven of the patients in the preliminary study and all of the 16
      acidotic patients in the prospective study were ultimately discharged from the
      hospital. CONCLUSIONS: This report documents the occurrence of lactic acidosis in
      a subgroup of patients undergoing cardiopulmonary bypass. The pathogenesis of
      this disorder is uncertain, but it appears to not relate to inadequate oxygen
      delivery. Systemic vasodilation and reduced oxygen extraction appear to be
      features of this disorder, which has an excellent prognosis.

PMID- 8989176
TI  - Quality of life after cardiac surgery complicated by multiple organ failure.
AB  - OBJECTIVE: To evaluate quality of life after prolonged multiple system intensive
      care treatment in cardiac surgical patients. DESIGN: A case-control study.
      SETTING: Adult 12-bed thoracic intensive care unit (ICU) at a university teaching
      hospital. PATIENTS: Forty-seven patients surviving multiple organ failure
      requiring intensive care treatment for > or = 5 days (ICU group). Patients with a
      completely uncomplicated postoperative course were matched to the study group
      with respect to gender, age, and type and date of surgery. The Nottingham Health
      Profile was used to assess quality of life at least 1 yr after complicated
      cardiac surgery. INTERVENTIONS: Quality of life measures were collected at least
      1 yr after discharge from the ICU. MEASUREMENTS AND MAIN RESULTS: Seventy-five
      percent of the patients in the ICU group suffered from multiple organ failure
      involving at least three organ systems, with a mean stay in the ICU of 9.0 +/-
      1.2 (SEM) days. Quality of life was considerably reduced in the ICU group, with a
      higher total mean score of all dimensions of quality of life (22.7 +/- 2.6)
      compared with the control group (13.2 +/- 2.4 [SEM])(p < .01). The Nottingham
      Health Profile score was higher in three of six dimensions of health--i.e.,
      energy (p < .05), physical mobility (p < .05), and emotional reactions (p < .05)-
      compared with the control group. A higher percentage of patients reported
      problems in three of six important activities of daily life--housework (p < .05),
      hobbies (p < .01), and sex life (p < .01)--compared with the control group.
      CONCLUSION: Patients treated with prolonged multiple system intensive care after
      heart surgery have a poor outcome with respect to quality of life measured at
      least 1 yr after discharge from the ICU.

PMID- 8989177
TI  - Effect of continuous venovenous hemofiltration with dialysis on lactate clearance
      in critically ill patients.
AB  - OBJECTIVE: To evaluate the effect of continuous venovenous hemofiltration with
      dialysis on lactate elimination by critically ill patients. DESIGN: Prospective,
      clinical study. SETTING: Surgical intensive care unit of a university hospital.
      PATIENTS: Ten critically ill patients with acute renal failure and stable blood
      lactate concentrations. INTERVENTIONS: Two-stage investigation: a) measurement of
      lactate concentrations in samples of serum and ultradiafiltrate from patients
      receiving continuous venovenous hemofiltration with dialysis to calculate lactate
      clearance by the hemofilter; b) evaluation of total plasma lactate clearance by
      infusing sodium L-lactate (1 mmol/kg of body weight) over 15 mins. MEASUREMENTS
      AND MAIN RESULTS: Arterial lactate concentration was determined before, during,
      and after the infusion. Lactate elimination variables were calculated from the
      plasma curve using model-independent and model-dependent estimates (by software).
      At the end of the infusion, median blood lactate concentration increased from 1.4
      mmol/L (range 0.8 to 2.6) to 4.8 mmol/L (range 2.4 to 5.7) and returned to 1.6
      mmol/L (range 0.9 to 3.4) 60 mins later. The median total plasma lactate
      clearance was 1379 mL/min (range 753.7 to 1880.7) and the median filter lactate
      clearance was 24.2 mL/min (range 7.1 to 35.6). Thus, filter lactate clearance
      accounted for < 3% of total lactate clearance. CONCLUSIONS: Continuous venovenous
      hemofiltration with dialysis cannot mask lactate overproduction, and its blood
      concentration remains a reliable marker of tissue oxygenation in patients
      receiving this renal replacement technique.

PMID- 8989178
TI  - Randomized, controlled trial of selective digestive decontamination in 600
      mechanically ventilated patients in a multidisciplinary intensive care unit.
AB  - OBJECTIVE: To evaluate the efficacy of two regimens of selective decontamination
      of the digestive tract in mechanically ventilated patients. DESIGN: Prospective,
      randomized, concurrent trial. SETTING: Multidisciplinary intensive care unit
      (ICU) in a 1,800-bed university hospital. PATIENTS: Consecutive patients (n =
      660) who were likely to require mechanical ventilation for at least 48 hrs were
      randomized to one of three groups: conventional antibiotic regimen (control group
      A); oral and enteral ofloxacin-amphotericin B (group B); and oral and enteral
      polymyxin E-tobramycin-amphotericin B (group C). Both treatment groups received
      systemic antibiotics for 4 days (ofloxacin in group B and cefotaxime in group C).
      INTERVENTIONS: Patients were randomized to receive standard treatment (control
      group A, n = 220), selective decontamination regimen B (group B, n = 220), and
      selective decontamination regimen C (group C, n = 220). After early deaths and
      exclusions from the study, 185 controls (group A) and 193 (group B)/200 (group C)
      selective decontamination regimen patients were available for analysis.
      MEASUREMENTS AND MAIN RESULTS: Measurements included colonization and
      primary/secondary infection rate, ICU mortality rate, emergence of antibiotic
      resistance, length of ICU stay, and antimicrobial agent costs. The study duration
      was 19 months. The patient groups were fully comparable for age, diagnostic
      category, and severity of illness. One third of patients in each group suffered a
      nosocomial infection at the time of admission. There was a significant difference
      between treatment group B and control group A in the number of infected patients
      (odds ratio of 0.42, 95% confidence interval of 0.27 to 0.64), secondary lower
      respiratory tract infection (odds ratio of 0.47, 95% confidence interval of 0.26
      to 0.82), and urinary tract infection (odds ratio of 0.47, 95% confidence
      interval of 0.27 to 0.81). Significantly more Gram-positive bacteremias occurred
      in treatment group C vs. group A (odds ratio of 1.22, 95% confidence interval
      0.72 to 2.08). Infection at the time of admission proved to be the most
      significant risk factor for subsequent infection in control and both treatment
      groups. ICU mortality rate was almost identical (group A 16.8%, group B 17.6%,
      and group C 15.5%) and was not significantly related to primary or secondary
      infection. Increased antimicrobial resistance was recorded in both treatment
      groups: tobramycin-resistant enterobacteriaceae (group C 48% vs. group A 14%, p <
      .01), ofloxacin-resistant enterobacteriaceae (group B 50% vs. group A 11%, p <
      .02), ofloxacin-resistant nonfermenters (group B 81% vs. group A 52%, p < .02),
      and methicillin-resistant Staphylococcus aureus (group C 83% vs. group A 55%, p <
      .05). Antimicrobial agent costs were comparable in control and group C patients;
      one third less was spent for group B patients. CONCLUSIONS: In cases of high
      colonization and infection rates at the time of ICU admission, the preventive
      benefit of selective decontamination is highly debatable. Emergence of multiple
      antibiotic-resistant microorganisms creates a clinical problem and a definite
      change in the ecology of environmental, colonizing, and infecting bacteria. The
      selection of multiple antibiotic-resistant Gram-positive cocci is particularly
      hazardous. No beneficial effect on survival is observed. Moreover, selective
      decontamination adds substantially to the cost of ICU care.

PMID- 8989179
TI  - Oxygen delivery, oxygen consumption, and gastric intramucosal pH are not improved
      by a computer-controlled, closed-loop, vecuronium infusion in severe sepsis and
      septic shock.
AB  - OBJECTIVE: To investigate the influence of the neuromuscular blocking agent
      vecuronium on oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction
      ratio, and gastric intramucosal pH in heavily sedated patients with severe sepsis
      or septic shock. DESIGN: Prospective, randomized, placebo-controlled, cross-over
      trial. SETTING: University hospital intensive care unit. PATIENTS: Eighteen
      mechanically ventilated patients with severe sepsis or septic shock.
      INTERVENTIONS: All patients were heavily sedated. After baseline measurement, a
      computer-controlled, closed-loop infusion of either vecuronium or saline was
      initiated and further measurements were made at 40 and 60 mins. The procedure was
      repeated with the alternative agent after return of neuromuscular function.
      MEASUREMENTS AND MAIN RESULTS: DO2, VO2, intramucosal pH were monitored using
      pulmonary artery catheters, a gas exchange monitor, and gastric tonometers.
      Changes from baseline were compared (paired t-test, p = .05). The vecuronium
      closed-loop infusion achieved T1 between 5% and 15% at 40 mins. There was a
      significant difference in the changes from baseline for static respiratory
      compliance in the vecuronium closed-loop infusion group compared with the saline
      closed-loop infusion group. There was no significant difference in the change
      from baseline for systemic or pulmonary vascular resistance, DO2, VO2, oxygen
      extraction ratio, or intramucosal pH. CONCLUSIONS: In these patients, vecuronium
      infusion achieved the targeted level of paralysis and improved respiratory
      compliance but did not alter intramucosal pH, VO2, DO2, or oxygen extraction
      ratios. With deep sedation, neuromuscular blockade in severe sepsis/septic shock
      does not significantly influence oxygen flux and should be abandoned as a routine
      method of improving tissue oxygenation in these patients.

PMID- 8989180
TI  - Skeletal muscle glutathione is depleted in critically ill patients.
AB  - OBJECTIVE: To investigate the concentrations of reduced and total glutathione in
      relation to the muscle free amino acid pattern in critically ill patients and
      matched healthy controls. DESIGN: Prospective case control. SETTING: University
      hospital intensive care unit (ICU). PATIENTS: Eleven critically ill patients in
      the intensive care unit were studied after a stay of at least 4 days. Eleven age-
      and gender-matched metabolically healthy patients undergoing elective surgical
      procedures served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Reduced and total glutathione concentrations were determined in skeletal
      muscle, in plasma, and in whole blood, together with muscle free amino acid
      concentrations. In the ICU group, reduced and total glutathione values were 57%
      and 62%, respectively, of the values seen in the control group (p < .001). In
      addition, a decreased ratio between reduced and total glutathione compared with
      the controls was seen (0.80 as compared with 0.91, p < .001). The glutamine
      concentration in skeletal muscle in the ICU group was 72% lower compared with
      that value seen in healthy controls (p < .001). Correlations were found between
      the concentrations of glutamine and the total muscle glutathione (r2 = .46, p <
      .001), as well as between glutamine and the ratio of reduced and total
      glutathione (r2 = .45, p < .001) in skeletal muscle, suggesting that the redox
      status of glutathione and the glutamine status of the tissue are related.
      CONCLUSIONS: Critical illness is associated with alterations in muscle
      glutathione metabolism. The muscle-reduced glutathione concentrations decrease
      and, in addition, the ratio between reduced and total glutathione decreases,
      indicating a situation of oxidative stress in this tissue. This decrease may
      impair the defense of muscle against oxygen free radicals and influence amino
      acid transport, thus contributing to the loss of balance between protein
      synthesis and protein degradation that is characteristic of protein catabolism.

PMID- 8989181
TI  - Urinary pyridinium cross-link excretion is increased in critically ill surgical
      patients.
AB  - OBJECTIVES: To determine: a) the rate of pyridinium cross-links of collagen
      excretion, breakdown products of bone, in critically ill surgical patients in the
      intensive care unit (ICU); and b) the relationship between cross-link excretion
      and nitrogen excretion and balance to ascertain whether collagen breakdown
      products contribute to protein losses during a hypercatabolic state. DESIGN:
      Observational study starting on the first postoperative day to 20 days or until
      discharge. SETTING: A surgical ICU in a University hospital. PATIENTS: Nine
      mechanically ventilated, postoperative surgical patients (73 +/- 3 [SD] yrs),
      receiving routine parenteral nutrition (18% protein) and 17 age-matched healthy
      subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Resting energy
      expenditure was determined daily for < or = 5 days after admission, and energy
      intake was set at 1.04 times the initial energy expenditure; thereafter, values
      of intake were reset weekly. Daily 24-hr urine samples were analyzed for cross
      links, total and urea nitrogen, calcium, and creatinine for 20 days or until
      discharge. Two urine samples were also analyzed for cross-links in the healthy
      subjects. The excretion of cross-links from the surgical patients was markedly
      higher (p < .001) than in the healthy subjects, and calcium balance was
      significantly negative (p < .05). Patients who were discharged from the ICU
      within 5 days showed a lower rate of cross-link excretion (p < .02) and less day
      to-day variability, compared with those patients who stayed longer, whether
      calculated over the course of the study or over the first 2 days in the ICU.
      There was no correlation between cross-links and energy expenditure, nitrogen
      excretion, or balance. CONCLUSIONS: The rate of cross-link excretion in
      critically ill patients: a) is markedly increased; b) is greater within the first
      two postoperative days in those patients who have an extended stay (> 5 days) in
      the ICU; and c) is independent of the rate of nitrogen excretion. These findings
      suggest that critically ill postoperative patients experience an acute breakdown
      of collagen, which is likely due to resorption of bone or possibly comes from
      other collagen sources.

PMID- 8989182
TI  - Influence of airway pressure on minimum occlusive endotracheal tube cuff
      pressure.
AB  - OBJECTIVE: To examine the in vivo relationship between peak inflation pressure
      and the minimum occlusive pressure of a "high-volume, low-pressure" endotracheal
      tube cuff that may in some circumstances promote tracheal ischemic complications.
      DESIGN: Prospective, clinical study. SETTING: Surgical suite in a university
      hospital. PATIENTS: Fifteen patients undergoing mechanical ventilation and
      general anesthesia for surgery. INTERVENTIONS: After the regularly assigned
      anesthesia personnel established adequate general anesthesia, the investigator
      deflated and then reinflated the endotracheal tube cuff until tracheal seal was
      reestablished by auscultation. Peak inflation pressure and minimum occlusive
      pressure were determined using fluid-filled transducers to simultaneously record
      airway pressure just proximal to the endotracheal tube and cuff pressure via the
      pilot tube. MEASUREMENTS AND MAIN RESULTS: Peak inflation pressure ranged from
      12.1 to 43.7 mm Hg, and was associated with a minimum occlusive pressure of 2.2
      to 39.7 mm Hg. Minimum occlusive pressure increased linearly over the range of
      measured peak inflation pressure values (r2 = .85, p < .001). CONCLUSIONS:
      Knowledge of the linear relationship between peak inflation pressure and minimum
      occlusive pressure can help the clinician identify patients who may be at risk
      for cuff-induced tracheal ischemic complications, such as tracheoesophageal
      fistula and tracheal stenosis. In our series, a cuff pressure of 25 mm Hg
      corresponded to a peak inflation pressure of 35.3 mm Hg (48 cm H2O). Patients
      with higher peak inflation pressures may be at risk for ischemic tracheal injury,
      despite proper cuff inflation techniques.

PMID- 8989183
TI  - Does age influence circulating adhesion molecules in the critically ill?
AB  - OBJECTIVE: Soluble adhesion molecules are regarded to be markers of inflammation,
      endothelial activation, or damage. The influence of age on plasma concentrations
      of circulating adhesion molecules should be serially studied in critically ill
      intensive care patients. DESIGN: Prospective and descriptive study over 5 days.
      SETTING: Clinical investigation in a surgical intensive care unit of a university
      hospital. PATIENTS: Thirty critically ill patients (Acute Physiology and Chronic
      Health Evaluation [APACHE] II score of > 15 points), with sepsis secondary to
      postoperative complications, were included in this study. Fifteen consecutive
      patients aged < 50 yrs and 15 consecutive patients aged > 70 yrs were
      prospectively studied. INTERVENTIONS: All patients were treated by the standard
      protocols of our intensive care unit, which did not differ between the groups.
      The patients received continuous analgesia-sedation and mechanical ventilation.
      Intensivists caring for the patients were not involved in the study and were
      blinded to data analysis. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters
      were extensively monitored in all patients. From arterial blood samples, plasma
      concentrations of soluble adhesion molecules (endothelial leukocyte adhesion
      molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1,
      granule membrane protein-140) were measured on the day of admission (i.e.,
      baseline values) and during the following 5 days. Three of the younger patients
      and six of the elderly patients died during the study period (p < .05). Oxygen
      delivery and consumption, and the other hemodynamic data, were without group
      differences throughout the study. Plasma concentrations of all adhesion molecules
      were beyond normal at baseline in both groups. These concentrations increased
      further during the first 2 to 3 days in both groups, with a significantly higher
      increase in the elderly patients (endothelial leukocyte adhesion molecule-1 to
      179 +/- 32 ng/mL; intercellular adhesion molecule-1 to 1695 +/- 158 ng/mL;
      vascular cell adhesion molecule-1 to 1395 +/- 212 ng/mL; and granule membrane
      protein-140 to 888 +/- 119 ng/mL). In the younger patients, concentrations of
      soluble adhesion molecules decreased later in the study and almost reached
      baseline values on day 5. In the elderly patients, these concentrations remained
      significantly higher until the end of the study. CONCLUSIONS: The higher plasma
      concentrations of the measured adhesion molecules in elderly critically ill
      patients indicate that elderly patients are more prone than younger patients to a
      more pronounced activation or even damage of the endothelium. Further work needs
      to be done to determine the prognostic importance and to define the role of
      soluble adhesion molecules, particularly in the elderly critically ill patient.

PMID- 8989184
TI  - A comparison of bactericidal/permeability-increasing protein variant versus
      recombinant endotoxin-neutralizing protein for the treatment of Escherichia coli
      sepsis in rats .
AB  - OBJECTIVE: To compare a recombinant bactericidal/permeability-increasing protein
      variant and a recombinant endotoxin-neutralizing protein. DESIGN: Randomized,
      blinded, controlled study, using a rat model of sepsis. SETTING: Animal research
      facility. SUBJECTS: Male Wistar rats. INTERVENTIONS: An inoculum of 1.5 x 10(7)
      to 1.8 x 10(8) Escherichia coli O18ac K1, implanted in the peritoneum, produced
      bacteremia in 95% of animals after 1 hr. One hour after E. coli challenge,
      animals received recombinant bactericidal/permeability-increasing protein
      variant, recombinant endotoxin-neutralizing protein, or saline intravenously,
      followed by ceftriaxone and gentamicin intramuscularly. MEASUREMENTS AND MAIN
      RESULTS: Twenty-four (85.7%) of 28 animals receiving recombinant endotoxin
      neutralizing protein (p < .001 vs. control) survived 7 days compared with nine
      (33.3%) of 27 recombinant bactericidal/permeability-increasing protein variant
      treated (p < .001 vs. control) and two (6.5%) of 31 control animals. CONCLUSIONS:
      Both recombinant endotoxin-neutralizing protein and recombinant
      bactericidal/permeability-increasing protein variant improved survival.
      Recombinant endotoxin-neutralizing protein was superior to recombinant
      bactericidal/permeability-increasing protein variant in its protective effect at
      the doses tested. Our results suggest that both proteins may be useful in the
      treatment of human Gram-negative sepsis.

PMID- 8989185
TI  - Females in proestrus state maintain splenic immune functions and tolerate sepsis
      better than males.
AB  - OBJECTIVES: To determine: a) whether the cell-mediated immune response during
      sepsis differs in females vs. males; and b) whether the survival rate in females
      is different than in males after a septic insult. DESIGN: A prospective,
      randomized animal study. SETTING: University research laboratory. SUBJECTS: Male
      and female proestrus C3H/HeN mice. INTERVENTIONS: After anesthesia, male and
      proestrus female mice underwent cecal ligation puncture to induce sepsis. The
      mice were killed at 24 hrs after the onset of sepsis. MEASUREMENTS AND MAIN
      RESULTS: Splenocyte proliferation, as well as splenocyte interleukin (IL)-2 and
      IL-3 release, was determined by bioassay. In additional studies, survival rate
      after septic challenge was measured over 10 days. Splenocyte proliferative
      capacity and splenocyte IL-2 and IL-3 release were markedly decreased in male,
      but not in female, septic mice. Furthermore, the survival rate of septic female
      proestrus mice was significantly higher than in comparable male mice.
      CONCLUSIONS: These results support the concept that the immune response of
      females differs from males, and that females are immunologically better
      positioned to meet the challenge of sepsis.

PMID- 8989186
TI  - The yeast to hyphal transition following hematogenous candidiasis induces shock
      and organ injury independent of circulating tumor necrosis factor-alpha.
AB  - OBJECTIVES: Dimorphic Candida albicans spp. increasingly cause lethal septic
      shock and disseminated infection in the critically ill. Following candidemia,
      production of specific fungal exotoxins coincident with the yeast to hyphal
      phenotypic transition is believed to be important in the pathogenesis of Candida
      septic shock. However, overexpression of the pleiotropic cytokine tumor necrosis
      factor (TNF)-alpha by the host following hyphal germination is also thought to be
      a mechanism of Candida-related cardiopulmonary dysfunction, as well as of
      bacteremic shock. In this study, we hypothesized that increases in circulating
      TNF-alpha coinciding with the yeast to hyphal transition modulate the onset and
      progression of shock with multiple organ injury early after hematogenous
      candidiasis. DESIGN: Prospective, controlled laboratory animal study. SETTING:
      University hospital animal research facility. SUBJECTS: Pathogen-free, male
      Sprague-Dawley rats (n = 26). INTERVENTIONS: Conscious, antibiotic-treated
      animals with chronic indwelling carotid arterial and jugular venous catheters
      were intravenously infected with 10(9) viable blastoconidia of the C. albicans
      clinical pathogen, CA-MEN (n = 10), over 30 mins and ending at t = 0 hr, compared
      with an equivalent inoculum of its viable agerminative mutant, CA-MM2002 n = 11),
      or an intravenous infusion of 0.9% sodium chloride (n = 5). MEASUREMENTS AND MAIN
      RESULTS: Mean arterial pressure (MAP), pulse rate, respiratory frequency, rectal
      temperature, acid-base status, quantitative blood cultures, circulating alanine
      aminotransferase (ALT), and bioactive TNF-alpha were serially measured in all
      three groups over 24 hrs or until death. Organ cultures, wet/dry weight ratios,
      and histopathologic changes in the lungs, heart, liver, and kidneys were
      determined in Candida-infected and 0.9% sodium chloride (normal saline)-infused
      subgroups at 6 and 24 hrs. Animals hematogenously infected with the C. albicans
      clinical isolate developed lethal nonendotoxemic shock in < or = 6 hrs (MAP 49 +/
      7 mm Hg [SEM]; p < .05 vs. t = 0 hr), and at death (7.0 +/- 0.3 hrs) were
      acidotic, hypocapnic, and hypothermic (rectal temperature 33.2 +/- 0.7 degrees
      C). Despite similar peak concentrations of circulating fungal colony-forming
      units (cfu) and kinetics of vascular clearance in both Candida-infected groups,
      survival and MAP in rats challenged with the agerminative C. albicans mutant were
      unchanged for > 8 hrs, as were pH, Pco2, and rectal temperature. No germination
      of the agerminative fungal strain occurred in vivo over 6 hrs. Serum TNF was
      nearly undetectable at t = 0 hr in all three groups. Although shock developed
      soon after fungemia with the C. albicans clinical isolate, TNF-alpha
      concentrations did not increase above normal saline values in either candidemic
      group at t = 1.5, 4.5, or 6 hrs (17 +/- 7 vs. 14 +/- 1 U/mL in the parent C.
      albicans organism vs. its agerminative mutant at t = 6 hrs). Greater numbers of
      agerminative C. albicans than its dimorphic parent strain were recovered from the
      lungs (5.41 +/- 1.0 vs. 2.02 +/- 0.38 x 10(7) cfu/g, respectively; p < .05) and
      kidneys (p < .01). By 24 hrs, modest germination of the mutant Candida strain was
      observed in the tissues. However, lung wet/dry ratios, intrapulmonary hyphal
      proliferation, and alveolar hemorrhage were all greater after infection with the
      parent fungal isolate. Likewise, myocardial necrosis and hepatic glycogen
      depletion with vacuolization were more severe after infection with the C.
      albicans clinical isolate vs. candidemia with its agerminative mutant, although
      serum ALT values did not differ between these groups. CONCLUSIONS: Lethal C.
      albicans sepsis with lung injury and multiple organ damage are temporally
      associated with the in vivo yeast to hyphal transition in this model. However,
      this candidemic septic shock syndrome is modulated by circulating fungal
      virulence factors or host mediators other than TNF-alpha, a cytokine considered
      essen

PMID- 8989187
TI  - Comparative effects of lipopolysaccharide on newborn versus adult rat hepatocyte
      and nonparenchymal cell cocultures.
AB  - OBJECTIVE: To examine the effects of development on the response of hepatocytes
      and nonparenchymal cells to an endotoxin challenge as an in vitro model of organ
      system dysfunction at differing developmental ages. DESIGN: In vitro animal cell
      culture model. SETTING: University teaching hospital research laboratory.
      SUBJECTS: Adult and newborn Sprague-Dawley rats. INTERVENTIONS: The method of
      hepatocyte and nonparenchymal cell coculture was utilized and modified to allow
      evaluation of cells derived from newborns. Cells were isolated from adult rats by
      standard perfusion technique. Hepatocytes and nonparenchymal cells were isolated
      from newborn rats by use of identical enzymatic degradation after fine mincing of
      the organ. Isolated cells were purified by density gradient. The hepatocytes were
      incubated in standard cell culture plates for 24 hrs before the addition of
      nonparenchymal cells. Hepatocytes were incubated with similar-age nonparenchymal
      cells. After an additional 24 hrs, serial log dilutions of lipopolysaccharide
      were added as a stimulus and the system was cultured an additional 24 hrs. The
      response of the hepatocytes was assessed by determination of 3H-leucine
      incorporation in acid-precipitated protein. In addition, the production of tumor
      necrosis factor, interleukin (IL)-1, and IL-6 by isolated nonparenchymal cells
      from adult and newborn rats was determined after stimulation with serial log
      dilutions of lipopolysaccharide by bioassay. MEASUREMENTS AND MAIN RESULTS: Both
      adult and newborn hepatocytes cocultivated with nonparenchymal cells demonstrated
      a comparable and statistically significant dose response to lipopolysaccharide (p
      < .01). The newborn hepatocytes demonstrated a greater rate of protein synthesis
      than the adult hepatocytes at all concentrations of lipopolysaccharide. Tumor
      necrosis factor production by newborn and adult nonparenchymal cells was similar
      at all lipopolysaccharide doses. IL-1 production demonstrated a positive dose
      response to lipopolysaccharide in the adult and newborn nonparenchymal cells,
      with a trend (p = .17) toward greater IL-1 secretion by the adult cells. There
      were significant differences in IL-6 production by isolated nonparenchymal cells
      at lipopolysaccharide doses of 0.01, 0.1, and 10 micrograms/mL. While a similar
      trend was apparent in the cocultured cells, the significance was not apparent,
      except at the highest lipopolysaccharide dose. CONCLUSIONS: The dose responses of
      newborn and adult hepatocytes to nonparenchymal cells stimulated with
      lipopolysaccharide were similar, although newborn hepatocytes appeared to have an
      inherently higher rate of protein synthesis compared with adult hepatocytes.
      Cytokine production was similar in nonparenchymal cells of both ages, although IL
      1 production by stimulated newborn nonparenchymal cells appeared to be less than
      IL-1 production by adult nonparenchymal cells.

PMID- 8989188
TI  - Tumor necrosis factor-alpha modulates the selective interference of hypnotics and
      sedatives to suppress N-formyl-methionyl-leucyl-phenylalanine-induced oxidative
      burst formation in neutrophils.
AB  - OBJECTIVE: To clarify whether tumor necrosis factor (TNF)-alpha modulates the
      inhibitory effect of clinically applied hypnotics and sedatives on neutrophil
      function. DESIGN: Prospective, randomized, controlled, dose response, in vitro
      study. SETTING: A university research laboratory. SUBJECTS: Neutrophils from
      healthy human volunteers. MEASUREMENTS AND MAIN RESULTS: Neutrophils were primed
      by incubation with TNF-alpha (25 ng/mL) for 15 mins. Subsequently, TNF-alpha
      primed neutrophils were incubated with two concentrations of commercially
      available drug preparations and drug-free solutions, respectively. The following
      commercially available preparations of hypnotics and sedatives as well as their
      corresponding drug-free solutions were tested: methohexital, thiopental,
      midazolam, diazepam, etomidate, and propofol. The production of oxygen radicals
      was initiated by adding N-formyl-methionyl-leucyl-phenylalanine (FMLP) 10(-7)
      mol/L and detected by luminol-enhanced chemiluminescence measurements for 15
      mins. Within the range of therapeutic plasma concentrations, only thiopental,
      diazepam, and propofol suppressed chemiluminescence of unprimed neutrophils.
      Additionally, propofol alone suppressed TNF-alpha-primed neutrophils. Hypnotics
      and sedatives were unable to suppress oxygen radical production of TNF-alpha
      primed neutrophils below the level of their control activity, measured in FMLP
      induced unprimed neutrophils in the absence of the respective drug or drug-free
      solution. However, the effect of etomidate could not be evaluated secondarily to
      effects mediated by its drug-free solution. In a cell-free chemiluminescence
      system, thiopental and propofol demonstrated scavenging of oxygen free radicals.
      CONCLUSIONS: Priming with TNF-alpha counteracts the inhibitory effect by certain
      drugs for oxygen radical formation by FMLP-stimulated neutrophils. Thus, TNF
      alpha plus FMLP mediate additive effects in stimulating oxygen radical formation
      in neutrophils. The following drugs dose-dependently interfere with these
      activating pathways: thiopental, diazepam, and propofol. Additionally, thiopental
      and propofol have efficient oxygen-scavenging properties and may attenuate
      radical-mediated tissue destruction in hyperinflammatory syndromes.

PMID- 8989189
TI  - Effects of dantrolene on cooling times and cardiovascular parameters in an
      immature porcine model of heatstroke.
AB  - OBJECTIVE: To evaluate the effects of dantrolene on cooling times and
      cardiovascular parameters in an immature porcine model of heatstroke. DESIGN:
      Prospective, randomized, controlled, multigroup study. SETTING: Research animal
      laboratory. SUBJECTS: Yorkshire piglets (n = 16), 4 to 5 wks of age, 3.5 to 4.5
      kg of body weight. INTERVENTIONS: Animals were slowly heated with a radiant heat
      source to 43 degrees C and then maintained at this temperature for 30 mins. The
      animals were then removed from the heat source and randomized into one of four
      groups to receive either conventional cooling methods consisting of fluid
      resuscitation with 0.9% sodium chloride solution, sponging with room temperature
      water, mechanical fanning, and gastric lavage with iced 0.9% sodium chloride
      solution (group 1), conventional cooling methods and dantrolene (group 2),
      conventional cooling methods and dantrolene's vehicle mannitol (group 3), or no
      treatment (group 4). Cooling times, defined as the time required to reach a core
      body temperature of 38.5 degrees C, and cardiovascular parameters for each group
      were then compared. MEASUREMENTS AND MAIN RESULTS: Animals in groups 1, 2, and 3
      had significantly (p < .05) lower core body temperatures than animals that
      received no treatment at the conclusion of the experiment. Piglets in groups 2
      and 3 had faster cooling times than piglets in group 1 (p < .05). However, there
      was no statistically significant difference in cooling times between the animals
      in groups 2 and 3. There were no statistically significant differences in heart
      rate, mean arterial pressure, central venous pressure, pulmonary artery occlusion
      pressure, or systemic vascular resistance index between animals in groups 1, 2,
      or 3. Group 3 piglets had higher cardiac indices and stroke indices than the
      piglets in the other groups (p < .05). CONCLUSIONS: Therapeutic interventions
      with conventional cooling or conventional cooling and dantrolene provided
      significant improvement in cardiovascular function in an immature porcine
      heatstroke model. Dantrolene, given with conventional cooling methods, offered no
      significant improvement in cardiovascular parameters compared with conventional
      cooling methods alone. Dantrolene significantly shortened the cooling time
      compared with conventional cooling but did not significantly shorten the cooling
      time compared with its vehicle, mannitol. Although dantrolene significantly
      shortened the cooling time, it did not appear to be superior compared with
      conventional cooling methods in treating heatstroke in this immature porcine
      heatstroke model.

PMID- 8989190
TI  - Delivery of metered dose inhaler aerosols to paralyzed and nonparalyzed rabbits.
AB  - OBJECTIVE: To assess whether paralysis alters pulmonary deposition of albuterol
      delivered by metered dose inhaler and spacer to small animals. DESIGN: A parallel
      group study of intubated and ventilated rabbits. INTERVENTIONS: Animals in group
      1 (n = 7) were paralyzed with intravenous pancuronium, and ventilated at a rate
      of 30 breaths/ min. The animals in group 2 (n = 6) were ventilated at a rate of
      10 breaths/min under light anesthesia without paralysis. In this latter group,
      spontaneous respiration continued at a rate of 40 to 50 breaths/min. Both groups
      were maintained at PaCO2 of 35 to 40 torr (4.7 to 5.3 kPa), and other ventilatory
      settings were identical. MEASUREMENTS AND MAIN RESULTS: Technetium-99m labeled
      albuterol aerosol was delivered by metered dose inhaler via a spacer device to
      both groups. Pulmonary deposition of the aerosol, determined by measuring the
      radioactivity in the lung tissues at autopsy, was expressed as percent of the
      total radioactivity dispensed by the metered dose inhaler. Group 2 showed
      significantly greater lung deposition than group 1 (0.510 +/- 0.076 [SEM]% vs.
      0.226 +/- 0.054%, p = .0094). Deposition in the airway, the endotracheal tube,
      and the ventilator circuit did not differ significantly. CONCLUSION: Metered dose
      inhaler delivery of aerosolized medications to ventilated rabbits is
      significantly enhanced if respiration is not controlled. This observation might
      have implications for the delivery of therapeutic aerosols to newborns and young
      infants receiving slow, intermittent, mandatory ventilation.

PMID- 8989191
TI  - Tracheal gas insufflation during pressure-control ventilation: effect of using a
      pressure relief valve.
AB  - OBJECTIVES: Pressure-control ventilation minimizes alveolar overdistention by
      limiting peak airway pressure, but a consequence of this pressure limitation may
      be a reduction in tidal volume with subsequent hypercarbia. Tracheal gas
      insufflation (TGI) can be used in combination with pressure-control ventilation
      to augment CO2 elimination. During pressure-control ventilation with continuous
      TGI, we observed that peak airway pressure increased above the set inspiratory
      pressure. Based on this observation, we investigated the ability of the pressure
      control ventilator circuit to compensate for continuous TGI and the effect of
      insertion of a pressure relief valve to eliminate over-pressurization. SETTING:
      University research laboratory. DESIGN: Using an artificial lung model, we
      studied the effects of continuous TGI with varying catheter flows (0, 2, 6, and
      10 L/ min); ventilator frequencies (10 and 20 breaths/min); inspiratory duty
      cycles (0.33, 0.50, and 0.67); lung compliance (0.01, 0.02, and 0.04 L/cm H2O);
      and airway resistance (5, 20, and 50 cm H2O/L/sec) on: a) peak airway pressure;
      b) total inspiratory tidal volume; c) ventilator-derived tidal volume; and d)
      intrapulmonary pressure at end-exhalation (auto-PEEP). Tests were performed with
      and without a pressure relief valve whose threshold "pop-off" pressure was
      adjusted to match the set inspiratory pressure (35 cm H2O) for a total of 432
      experimental conditions. MEASUREMENTS AND MAIN RESULTS: Our data demonstrate that
      pressure-control ventilation augmented with continuous TGI can increase peak
      airway pressure above set inspiratory pressure due to delivery of a higher than
      intended tidal volume. Predisposing conditions include catheter flow rates of 6
      and 10 L/min, long inspiratory time, low compliance, and low resistance. With the
      pressure relief valve, peak airway pressure was maintained at the set inspiratory
      pressure and total inspiratory tidal volume remained constant. CONCLUSION: A
      pressure relief valve is a necessary adjunct to maintain peak airway pressure at
      set inspiratory pressure and keep total inspiratory tidal volume constant when
      continuous TGI is administered in conjunction with pressure-control ventilation.

PMID- 8989192
TI  - Efficacy of inhaled nitric oxide in oleic acid-induced acute lung injury.
AB  - OBJECTIVE: To assess the efficacy of inhaled nitric oxide in improving pulmonary
      hypertension and gas exchange following oleic acid-induced acute lung injury.
      DESIGN: Prospective, pharmacologic study. SETTING: Surgical research laboratory
      at the University of Pittsburgh, Pittsburgh, PA. SUBJECTS: Instrumented,
      intubated pigs weighing 16 to 27 kg. INTERVENTIONS: Intravenous oleic acid and
      inhaled nitric oxide. MEASUREMENTS AND MAIN RESULTS: All pigs treated with
      intravenous oleic acid (0.11 mL/kg) developed a severe lung injury with pulmonary
      hypertension, accompanied by impaired oxygenation, intrapulmonary shunting, and
      increased extravascular lung water (p < .05 compared with baseline). Following
      nitric oxide inhalation, although pulmonary hypertension decreased in a dose
      dependent fashion, no amelioration in pulmonary gas exchange was observed, as
      reflected by PaO2 and intrapulmonary shunt. Plasma nitrite and nitrate
      concentrations, the stable end products of nitric oxide metabolism, did not
      increase following nitric oxide exposure in this model of severe lung injury.
      CONCLUSIONS: The effect of inhaled nitric oxide, restricted to relieving
      pulmonary vasoconstriction in this model of lung injury, may have limited benefit
      in improving pulmonary gas exchange when diffusion is impaired by severe lung
      injury and inflammatory thickening of the alveolar-capillary barrier. Nitric
      oxide inhalation may have better results when used at an earlier, less severe
      stage of acute lung injury.

PMID- 8989193
TI  - Basal nutrition promotes human intestinal epithelial (Caco-2) proliferation,
      brush border enzyme activity, and motility.
AB  - OBJECTIVES: Provision of nutrients to the apical membrane of intestinal
      epithelial cells by the enteral route is critical for normal gut mucosal function
      and for the sheet migration required for mucosal healing. The present work
      attempts to determine whether supplemental nutrient delivery to the basal
      epithelial surface is important for intestinal epithelial biology. Since attempts
      to regulate intestinal epithelial cell biology by manipulation of parenteral
      nutrition solutions have met with some success, we hypothesized that basally
      delivered nutrients might also be important for intestinal epithelial biology.
      DESIGN: To test this hypothesis, we compared the brush border enzyme activity,
      proliferation, and motility of human intestinal epithelial (Caco-2) cells
      cultured on a type I collagen substrate either on cell culture dishes with
      culture medium above the apical side of the cell monolayer or in culture inserts
      on 0.45-mu semipermeable membranes with culture medium beneath the monolayers as
      well as above them. Proliferation was assessed by serial hematocytometric counts
      over 13-day period. Doubling times were calculated by logarithmic transformation
      of cell counts 48 hrs apart. The specific activity of the brush border enzymes,
      dipeptidyl dipeptidase and alkaline phosphatase, was assayed by the digestion of
      synthetic chromogenic substrates in protein-matched aliquots of cell lysates.
      Sheet migration was quantitated by the expansion of Caco-2 monolayers across
      collagen. Motility was dissociated from the proliferative component of monolayer
      expansion by blocking proliferation with mitomycin C. SETTING: Laboratory for
      gastrointestinal mucosal biology. SUBJECTS: A well-differentiated subclone of
      cells derived from the established human Caco-2 colonic epithelial cell line.
      MEASUREMENTS AND MAIN RESULTS: Basal nutrient delivery promoted Caco-2
      proliferation, brush border enzyme activity, monolayer expansion, and cell
      motility. Proliferation was actually increased by 694 +/- 9.89% (n = 90, p <
      .0001) in cells nourished apically and basally compared with a 314 +/- 3.31%
      increase (n = 90, p < .0001) in those cells receiving only apical nutrition. The
      addition of basal nutrient delivery to the cell culture system augmented both
      alkaline phosphatase and dipeptidyl dipeptidase specific activity by 116 +/- 5.4%
      and 256 +/- 14.0%, respectively (p < .0001, n = 6 for each group). The effects of
      basal nutrient delivery were maintained after mitomycin blockade of proliferation
      for both alkaline phosphatase (392 +/- 89.8% of control, n = 3, p < .0005) and
      dipeptidyl dipeptidase (374 +/- 79.1% of control, n = 3, p < .005), suggesting
      that the increased digestive enzyme-specific activity reflected differentiation
      rather than indirect effects of slowing of proliferation. Epithelial sheet
      migration increased by 389 +/- 8.8% and proliferation-blocked cell motility also
      increased by 76.5 +/- 1.56% (p < .0005, n = 12 for each) compared with apical
      nutrient delivery only. CONCLUSIONS: These results suggest that although apical
      nutrition may be critical for intestinal epithelial cell biology, nutrient
      delivery to the basal surface of intestinal epithelial cell membranes may also
      promote intestinal epithelial differentiation, proliferation, and mucosal
      healing.

PMID- 8989194
TI  - Near-infrared spectroscopy: continuous measurement of cytochrome oxidation during
      hemorrhagic shock.
AB  - OBJECTIVE: Mitochondrial cytochrome a,a3 redox shifts can be determined by near
      infrared wavelength reflection. Since near-infrared wavelengths penetrate skin
      and bone, a potential exists to noninvasively measure mitochondrial oxidation
      using this phenomenon. The purpose of this study was to compare conventional
      parameters of resuscitation with regional measurements of spectroscopically
      derived cytochrome redox state in a hemorrhagic shock model. DESIGN: Prospective,
      controlled laboratory investigation. SETTING: Animal research laboratory of a
      university medical center. SUBJECTS: New Zealand white rabbits (n = 23), weighing
      2 to 3 kg. INTERVENTIONS: After anesthesia and instrumentation, the subjects
      underwent laparotomy with placement of near-infrared spectroscopy probes on the
      stomach, liver, kidney, and hamstring muscle. Baseline measurements were
      obtained, and phlebotomy was used to reduce cardiac output by 60% for 30 mins.
      Animals were resuscitated with shed autologous blood and crystalloid to reach
      baseline cardiac output (0.9%), and were monitored for an additional 60 mins.
      MEASUREMENTS AND MAIN RESULTS: Significant correlations between mitochondrial
      cytochrome a,a3 redox state, cardiac output, and oxygen delivery were observed
      throughout shock and resuscitation. However, gastric cytochrome oxidation did not
      recover after shock, despite systemic evidence of adequate resuscitation (p <
      .05). CONCLUSIONS: Resuscitation from severe hemorrhagic shock may not uniformly
      restore cellular oxygenation, despite normalization of traditional parameters of
      resuscitation. Direct monitoring of cytochrome oxidation may be useful in
      identifying regional areas of dysoxia.

PMID- 8989195
TI  - Technical and methodologic considerations for performance of indirect calorimetry
      in ventilated and nonventilated preterm infants.
AB  - OBJECTIVE: To evaluate and refine indirect calorimetry measurement techniques so
      that accurate metabolic measurements can be performed in mechanically ventilated
      and convalescing preterm infants who require supplemental oxygen. DESIGN:
      Laboratory validation of an indirect calorimeter; clinical and laboratory
      assessments of technical problems in performing metabolic measurements; and
      clinical indirect calorimetry studies in mechanically ventilated and
      nonventilated preterm infants. SETTING: Neonatal intensive care unit (ICU) in a
      tertiary care university hospital. PATIENTS: Level II and level III mechanically
      ventilated (n = 10) and nonventilated (n = 14) neonatal ICU patients who required
      FIO2 levels ranging from 0.21 to 0.42. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: System calibration was assessed by combustion of 100% ethanol; the mean
      respiratory quotient was 0.667 +/- 0.001 (SEM). In addition, oxygen consumption
      (Vo2) and CO2 production (Vco2) were simulated by CO2/nitrogen infusions within
      the range expected for 0.5- to 7-kg infants. Mean relative errors were 0.6 +/-
      0.3% and 1.8 +/- 0.3% for expected Vo2 and Vco2 values, respectively. In 27
      mechanically ventilated patients with no audible endotracheal tube leak, measured
      endotracheal tube leak ranged from 0.0% to 7.5%. Fluctuations in FIO2 during
      mechanical ventilation were monitored in 30-min studies, using wall-source (n =
      27) or tank-source (n = 11) supplemental oxygen. Mean FIO2 variation was 0.00075
      +/- 0.00013 vs. 0.00011 +/- 0.00001 using wall-source and tank-source oxygen,
      respectively. Some of the difficulties of obtaining accurate measurements in
      supplemental hood oxygen studies were overcome by using tank-source vs. wall
      source oxygen and a unique hood design. CONCLUSIONS: Accurate indirect
      calorimetry studies can be performed in both ventilated and nonventilated infants
      weighing as little as 500 g, providing that sufficient attention is paid to
      technical and methodologic measurement details.

PMID- 8989196
TI  - Alterations in dopamine clearance and catechol-O-methyltransferase activity by
      dopamine infusions in children.
AB  - OBJECTIVE: To determine the role of catechol-O-methyltransferase (COMT) in the
      biodisposition of pharmacologic concentrations of dopamine. DESIGN: The study was
      an open-label dose escalation trial in which dopamine was employed as the sole
      exogenous catecholamine. The dosage was adjusted to achieve improvements in
      cardiac output or to augment renal function. SETTING: A 16-bed pediatric
      intensive care unit serving both medical and surgical patients. PATIENTS: The
      study was performed using 14 dopamine-treated and five untreated control
      patients. Children ranged in age from 16 days to 12 yrs; five of the treated
      patients and two of the untreated controls were female. All but one of the study
      patients were enrolled within 24 hrs of palliative or corrective surgery for
      congenital heart disease. Control patients had noncardiac surgical procedures.
      Both treated and control groups were similar with respect to severity of illness,
      as judged by Therapeutic Intervention Scoring System score. INTERVENTIONS: All
      treated patients received dopamine as a continuous intravenous infusion. Infusion
      rates were determined by caregivers and ranged from 3.0 to 20 micrograms/kg/min.
      MEASUREMENTS AND MAIN RESULTS: Serial, timed blood samples were obtained from
      patients and control subjects for the determination of plasma dopamine
      concentrations and for the determination of mononuclear cell COMT activity.
      Measured rates of dopamine infusion (3.0 to 18.3 micrograms/kg/min) were
      consistently less than the nominal rates (3.0 to 20.0 micrograms/kg/min) of
      infusion (p < .0001) due in part to calculations based on the hydrochloride salt
      rather than dopamine base. At similar steady-state infusion rates, plasma
      dopamine concentrations varied over a four-fold range, with steady-state
      concentrations at even the lowest infusion rate exceeding endogenous
      concentrations by at least ten-fold. Variations in steady-state plasma dopamine
      concentration reflected large age-associated variations in dopamine clearance,
      which was found to be saturable at concentrations of > 200 ng/mL. Mononuclear
      cell COMT activity was assessed simultaneously in these patients. Baseline COMT
      activity varied over a six-fold range and was unrelated to dopamine clearance or
      patient age. COMT activity increased two- to six-fold in dopamine-treated
      patients with plasma steady-state dopamine concentrations of > 100 ng/mL.
      CONCLUSIONS: These data demonstrate marked age and concentration-dependent
      differences in dopamine clearance that account for large interindividual
      differences in the steady-state plasma dopamine concentrations in patients
      receiving similar infusion rates. While concomitant variability in COMT activity
      is observed, the lack of correlation between dopamine clearance and COMT activity
      suggests that COMT is not rate-limiting for the clearance of exogenously
      administered dopamine.

PMID- 8989197
TI  - A delivery system for inhalation of nitric oxide evaluated with
      chemiluminescence, electrochemical fuel cells, and capnography.
AB  - OBJECTIVE: To evaluate a system for delivery of inhaled nitric oxide. DESIGN:
      Prospective, laboratory study. SETTING: Engineering laboratory. SUBJECTS: A
      standard ventilator (Servo Ventilator 300), supplemented with extra gas modules
      for nitric oxide delivery. INTERVENTIONS: Two ventilator-integrated gas modules,
      delivering < or = 10 parts per million (ppm) or < or = 100 ppm of nitric oxide,
      were used in adult and neonatal modes during volume-controlled ventilation. Set
      nitric oxide concentration and FIO2 were systematically changed and compared with
      the measured concentration. Short-term mixing was tested in adult, pediatric, and
      neonatal modes by substituting nitric oxide with CO2, and measuring the delivered
      concentration by a fast-response CO2 analyzer during five successive respiratory
      cycles. Long-term mixing was tested with the administration of 25 ppm of nitric
      oxide for 7 days. MEASUREMENTS AND MAIN RESULTS: Delivered concentration of
      nitric oxide and nitrogen dioxide were simultaneously measured at the Y-place by
      two methods-chemiluminescence and electro-chemical fuel cells. The maximum
      absolute difference between set and measured concentrations of nitric oxide in
      the adult mode was 0.6 ppm at a set concentration of 10 ppm and 2.7 ppm at a set
      concentration of 100 ppm. In the neonatal mode, the maximal difference was 3.1
      ppm at a set concentration of 100 ppm. Nitrogen dioxide concentration increased
      with increasing concentration of nitric oxide and oxygen to 2.6 ppm (as measured
      by the chemiluminescence analyzer) and 3.6 ppm (as measured by the electro
      chemical fuel cell), at a setting of 100 ppm of nitric oxide with an FIO2 of 0.90
      in the neonatal mode (2 L/min). During the short-term test of mixing stability
      throughout the respiratory cycles, a constant set CO2 concentration varied
      maximally by +/-6.2% from the set value in the neonatal mode, whereas the
      variance was by +/-6.5% in pediatric mode, and by +/-8.0% in the adult mode.
      During the long-term test, nitric oxide concentration varied maximally by +/-2.6%
      (as measured by the chemiluminescence analyzer) and by +/-2.3% (as measured by
      the electrochemical fuel cell). CONCLUSIONS: An accurate precision in delivered
      nitric oxide concentration was achieved during intermittent flow ventilation, and
      this accuracy was independent of tested ventilator settings. The delivery system
      administered an almost stable concentration throughout a respiratory cycle and
      during long-term delivery. If the mixing point is in the inspiratory part of the
      ventilator, valid measurement of nitric oxide and nitrogen dioxide delivery
      concentrations are possible. Both techniques for measuring nitric oxide and
      nitrogen dioxide have drawbacks.

PMID- 8989198
TI  - Experience with an end-of-life practice at a university hospital.
AB  - OBJECTIVE: To describe a 10-yr experience with an end-of-life practice in a
      hospital. DESIGN: A nonexperimental, prospective, descriptive design was used to
      record variables from a convenience sample of patients transferred to the
      Comprehensive Supportive Care Team. SETTING: Detroit Receiving Hospital is an
      urban, university-affiliated, Level I trauma/emergency hospital. PATIENTS:
      Patients who are not expected to survive hospitalization, and for whom a decision
      has been made to focus care on palliative interventions, are candidates for care
      by this practice. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient
      demographics, including the following information: age, gender; diagnoses;
      illness severity; mortality rate; and disposition. Measures of resource
      utilization included: referral sources; Therapeutic intervention Scoring System
      values; bed costs; and length of hospital stay. Satisfactory patient/family care
      with a measurable reeducation in the use of resources can be achieved in the
      hospital setting. CONCLUSIONS: A hands-on approach to the care of dying patients
      by this specialty, palliative care service has provided patients, families, and
      clinicians with the type of support needed for satisfactory end-of-life care. A
      summary of our experience may be useful to others.

PMID- 8989199
TI  - Effects of pentoxifylline in patients with septic shock.

PMID- 8989200
TI  - Volume-controlled versus biphasic positive airway pressure.

PMID- 8989201
TI  - Nitric oxide does not influence tissue oxygen extraction capabilities in low
      cardiac output.

PMID- 8989202
TI  - Society of Critical Care Medicine 26th educational and scientific symposium. San
      Diego, California, February 6-10, 1997.

PMID- 8989204
TI  - Comparative analysis of the gp120-binding area of murine and human CD4 molecules.
AB  - The structural basis for the difference between human and murine CD4 molecules in
      binding to HIV envelope protein gp120 has been intensively studied. Eighteen
      mutant human CD4 molecules were produced by segmental replacement of beta strands
      and loops in the gp120-binding area of the molecule with corresponding murine
      sequences or by single amino acid substitutions. Examination of these mutant CD4
      molecules for gp120 binding indicated that murine CD4 molecule does not bind
      gp120 for the following three reasons: (a) The loops flanking the C" strand are
      longer than their human counterparts, causing significant difference in local
      tertiary structure; (b) valin, rather than phenylalanine, which is the key amino
      acid for the binding occupies position 43; (c) amino acids at positions 45 and 46
      are different, causing further decrease in binding affinity. Furthermore, the
      present study indicated that the aromatic ring of Phe43 and the negative charge
      of Arg59 play key roles in gp120 binding.

PMID- 8989203
TI  - Genetic, antigenic and serologic characterization of human immunodeficiency virus
      type 1 from Indonesia.
AB  - To examine the genetic and antigenic characteristics of HIV-1 in Indonesia,
      samples from 19 HIV-positive volunteers were studied. By a combination of PCR
      typing and DNA sequence analysis, 12 of the 19 volunteers were determined to be
      infected with HIV-1 clade B and seven with clade E. Six of the seven Indonesian
      clade E isolates were from volunteers associated with the Indonesian Military
      during a peacekeeping mission in Cambodia. Infectivity reduction neutralization
      assays showed that the Indonesian E viruses were effectively neutralized by
      Thailand clade E HIV-1 antisera but not by U.S. clade B antisera. The Indonesian
      clade B virus tested was neutralized by U.S. clade B antisera and not by the
      Thailand E antisera. Using a previously described serologic typing ELISA based on
      clade B and E V3 peptides, genetic clade was accurately determined in eight of
      eight sera tested. This is the first report of the genetic and antigenic analysis
      of HIV-1 isolates from Indonesia. The data indicate that at least two genetic and
      antigenic HIV-1 clades (clade E and B) circulate in Indonesia.

PMID- 8989205
TI  - Tenidap inhibits replication of the human immunodeficiency virus-1 in cultured
      cells.
AB  - Interleukin-6 (IL-6) may be important in the pathogenesis of HIV-1 because of its
      ability to induce HIV-1 expression in infected cells in vitro. Tenidap, a
      structurally and functionally novel antirheumatic drug affecting diverse biologic
      processes, has been shown to reduce IL-6 production by peripheral blood
      mononuclear cells stimulated with lipopolysaccharide. Tenidap also inhibits the
      activity of chloride-bicarbonate exchangers and causes acidification of the
      cytoplasmic compartment that is similar to the effect of the anion transport
      inhibitor UK5099. Furthermore, tenidap inhibits the cyclooxygenase-mediated
      pathway of arachidonic acid metabolism as do the nonsteroidal antiinflammatory
      drugs (NSAIDs). Here we show that tenidap decreased HIV-1 replication as measured
      by p24 core antigen in the acutely infected CD4+ T-lymphocyte lines H9 and
      Jurkat, in the acutely infected monocyte line U937, and in its chronically
      infected subclone U1.8/HIV. These effects were seen at concentrations in the
      range of 3 to 15 microM, well below those toxic to cells. The antiviral effects
      of tenidap may be independent of its ability to reduce IL-6 production based on
      the observations that these effects were as prominent in IL-6 nonresponsive lines
      as in IL-6 responsive lines and that the inhibition of p24 production was not
      reversed by exogenous IL-6.

PMID- 8989206
TI  - Enhancement of monocyte migration and phagocytosis by the bovine immunodeficiency
      like virus Gag proteins.
AB  - Supernatants from bovine immunodeficiency-like virus (BIV)-infected cells have
      been previously shown to affect monocyte random migration, chemotaxis,
      phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.
      The experiments in this report demonstrate that the BIV Gag (core) proteins can
      enhance monocyte random migration, chemotaxis, and phagocytosis. Supernatants
      from BIV-infected cells contained 10-30 and 30-50 kDa proteins, which
      significantly (p < 0.05) increased monocyte chemotaxis. The 30-50 kDa protein(s)
      could be cleaved by limited proteolysis into 10-30 kDa active components.
      Affinity purification with monoclonal anti-p26 (capsid) antibodies yielded
      preparations that were active in the random migration, chemotaxis, and
      phagocytosis assays, but did not affect ADCC. Furthermore, activity of the
      affinity purified preparation could be specifically neutralized by hyperimmune
      rabbit serum against BIV Gag proteins. A recombinant Gag protein, consisting
      primarily of BIV p26, also enhanced monocyte random and chemotactic migration. It
      appears, therefore, that direct treatment with affinity-purified BIV Gag proteins
      or a recombinant Gag protein, is able to significantly affect the function of
      normal monocytes in vitro. Factors affecting monocyte migration and phagocytosis
      appear to be one or more breakdown products of the BIV Gag precursor,
      particularly those containing the p26 (capsid) protein.

PMID- 8989208
TI  - A whole blood alternative to traditional methods for CD4+ T lymphocyte
      determination.
AB  - Flow cytometry, the method of choice for determining subset cell populations,
      requires sophisticated instrumentation and highly trained operators. An
      alternative method for subpopulation determinations is presented that is fast,
      simple, and readily interpreted for absolute subset counts. This method uses
      antibody labeled microspheres added to whole blood and after lysing, read on a
      hemocytometer using an ordinary light microscope. The total time of testing is
      less than 10 min with results comparable to that obtained using a flow cytometer
      and a hematology analyzer to calculate absolute subpopulation values. This method
      is demonstrated for CD4+ lymphocytes which have considerable value in following
      HIV-infected individuals.

PMID- 8989207
TI  - Vertical HIV-1 transmission correlates with a high maternal viral load at
      delivery.
AB  - Transmission of HIV-1 from an infected mother to her child occurs in around 20%
      of cases. Although maternal, immunological, and virological factors have been
      implicated in transmission, clear association is not yet well defined. For this
      reason, we have conducted a study to determine the relative contribution of the
      above-mentioned factors with special emphasis on quantitative viral load. We
      studied 67 HIV-1-infected mothers during pregnancy and labor and their 69
      newborns (two sets of twins) from two university hospitals in Barcelona. Plasma
      and cell samples were collected at delivery between January 1992 and May 1994,
      and HIV-1 RNA and p24 in plasma, CD4 cell counts, and tissue culture infectious
      doses (TCID) were measured. Diagnosis of infection in children was based on
      persistence of anti-HIV-1 antibodies at 18 months of age, a positive HIV-1
      culture or polymerase chain reaction in two separate samples, or presence of
      signs or symptoms of AIDS before 18 months of age. Results showed a very high
      relationship between > 10(5)/ml viral RNA copies (odds ratio [OR] 22, 95%
      confidence interval [CI] 4.4-119.2, p < 0.00001), > 0.5 TCID (OR 17, 95% CI 2.1
      139.7, p = 0.001), CDC B + C (OR 3.5, 95% CI 0.98-12.5, p = 0.055), < 400 CD4
      cells (OR 4.1; 95% CL 1.1-15.4, p = 0.01) and transmission of HIV-1. In this
      study, a strong association between mother-to-child transmission of HIV-1 and a
      high maternal viral RNA load in plasma at delivery is demonstrated. Viral load,
      which is related to clinical and immunological status in the mother, is the main
      contributing factor for HIV-1 vertical transmission, and these findings may have
      global and even individual therapeutic implications.

PMID- 8989209
TI  - Insurance type and satisfaction with medical care among HIV-infected men.
AB  - Patient satisfaction is a valuable indicator of the quality of medical care. We
      assessed the impact of type of health insurance on satisfaction with seven
      aspects of medical care among 593 HIV-infected men without AIDS, drawn from three
      sites in San Francisco, California and Denver, Colorado. After adjustment for
      site of medical care, patient age, race, income, education, and CD4 lymphocyte
      count, there were few differences in satisfaction between men with fee-for
      service and those with managed care insurance. Men with fee-for-service insurance
      were significantly more satisfied with their interpersonal relations with their
      clinicians (p = 0.01) but less satisfied with their finances (p = 0.0001) than
      persons with managed care. Uninsured men were significantly less satisfied with
      several aspects of care than insured persons. There were no significant
      differences in satisfaction between men with managed care and those with public
      insurance. HIV-infected persons who have a choice of insurance should carefully
      weigh their options, recognizing the implicit trade-offs between types of
      insurance. Those who choose fee-for-service insurance can expect to be more
      satisfied with interpersonal relations with their medical providers but less
      satisfied with financial aspects of their plans. Efforts to address the low
      satisfaction of uninsured persons are needed.

PMID- 8989210
TI  - Meeting the service needs of HIV-infected persons: is the Ryan White CARE Act
      succeeding?
AB  - To evaluate the success of the Ryan White CARE Act in meeting HIV-related service
      needs, we surveyed HIV-infected clients (n = 1,056) at San Francisco CARE-funded
      agencies. Most CARE clients were male (85.1%), 51.7% were nonwhite, 84.9% were
      uninsured or underinsured, and 43.9% had a most recent CD4+ count < 200 cells.
      The most common HIV risk groups were gay/ bisexual male noninjection drug user
      (IDU) (53.3%) and gay/bisexual male IDU (22.1%). Health care needs were high for
      medical (85.5%), dental (70.2%), and mental health care (69.7%); need for basic
      necessities was great for food (57.2%) and living expenses (55.5%). Unmet health
      care needs were common for dental care (41.0%), home health care (39.9%), and
      alternative therapies (38.6%); unmet needs for basic necessities were frequent
      for childcare (59.5%), household help (52.3%), and transportation (47.9%). Unmet
      needs for medical care (5.8%) and food (14.7%) were low. Poor persons, those with
      dependents, and gay/bisexual male IDUs had greater unmet needs. Women and
      racial/ethnic minorities did not consistently have greater unmet needs. The CARE
      Act is serving those it intended to reach, is successfully meeting two important
      service needs, and has equalized access to services for women and racial/ethnic
      minorities. Remaining unmet needs require continued funding and strategies to
      increase access to care.

PMID- 8989211
TI  - Impact of laboratory-initiated reporting of CD4+ T lymphocytes on U.S. AIDS
      surveillance.
AB  - This study was conducted to measure the impact of laboratory-initiated reporting
      of CD4+ results on reporting of AIDS in the United States. States were
      categorized by whether CD4+ reporting was required; we compared the number and
      percentage of AIDS cases reported based on immunologic criteria, controlling for
      whether states also required HIV infection reporting. We observed cases reported
      in 1994 with CD4+ values and the delay between diagnosis and report by CD4+ and
      HIV-reporting status. From 1992 to 1994, states with CD4+ reporting had a greater
      proportionate increase in reported AIDS cases (98%) than states without CD4+
      reporting (55%; p < 0.0001). From 1993 to 1994, the eight states with both CD4+
      and HIV reporting had a higher increase in cases meeting immunologic criteria
      (7%) than the 13 states with only HIV reporting (< 1%), the three states with
      only CD4+ reporting (< 1%), and the 16 states with neither form of laboratory
      reporting (4%). Of 1987 definition cases reported in 1994, the percentage
      reported with CD4+ values was lower in states without either CD4+ or HIV
      reporting (79%) than in states with both CD4+ and HIV reporting (83%), only HIV
      reporting (84%), or only CD4+ reporting (88%). The percentage of AIDS cases
      reported within 3 months of diagnosis was lower in states without laboratory
      reporting (40%) than in states with CD4+ reporting (45%, p = 0.001). CD4+
      reporting may enable states to report AIDS cases earlier in the course of HIV
      disease, permitting early targeting of health care and social services.

PMID- 8989212
TI  - Rates of and factors associated with self-reported prior HIV testing among adult
      medical patients in an inner city emergency department in the Bronx, New York
      City.
AB  - We studied the rates of and factors associated with self-reported prior human
      immunodeficiency virus (HIV) testing in adult patients visiting an emergency
      department (ED) in the Bronx, New York City. A total of 1,744 consecutive
      noncritical adult medical emergency patients responded to a standardized
      interview administered by ED physicians. The interview included questions
      pertaining to demographic characteristics, prior HIV testing, and HIV risk
      behaviors. On multivariate analysis, female gender, younger age, history of
      weight loss, injecting drug use (IDU), syphilis, and genital herpes were all
      associated with increased reported prior testing rates. Race (i.e., black race)
      was an independent predictor of increased rates among male subjects;
      comparatively low rates were reported by patients with a first language other
      than English, patients lacking medical insurance, and highly sexually active,
      nonblack men. Increased HIV testing rates were reported by subjects with
      recognized HIV risk behaviors in a New York City ED population; however,
      substantial proportions of subjects at risk had not been tested. Programs of HIV
      testing and counseling need to include older, uninsured, and non-English-speaking
      segments of the population who engage in high-risk behaviors.

PMID- 8989213
TI  - Retroviral coinfections at a New Orleans HIV outpatient clinic.
AB  - The purpose of the study was to determine the seroprevalence of human T
      lymphotropic virus types I and II (HTLV-I and HTLV-II) infections in an
      outpatient clinic population of human immunodeficiency virus (HIV)-1 infected
      persons as well as to identify the demographic and clinical characteristics and
      laboratory results associated with HTLV-I/II infections. During 1993-1995, 854
      patients were tested for HTLV-I/II infection on entry into the clinic, of whom 25
      were infected with HTLV-I and 35 with HTLV-II. Multivariate analysis revealed
      that patients with coinfections were more likely to be black, aged over 35 years,
      and have a history of injection drug use. HIV-1/HTLV-I coinfections were
      associated with higher median CD8 counts on entry (p < 0.05), and HIV-1/HTLV-II
      coinfections were associated with higher median percent CD4 counts (p < 0.05)
      compared with patients infected with HIV only. Coinfection was not associated
      with an increased diagnosis of AIDS. These findings indicate that HIV-1/HTLV-I/II
      coinfections are frequently diagnosed and are associated with unique immune
      phenotypes. Given the lack of information regarding the influence of dual
      infection on clinical status, differentiation of HTLV-I from HTLV-II infections
      may be important in understanding the clinical significance of retroviral
      coinfections.

PMID- 8989214
TI  - Differences in sexual behavior among HIV discordant and concordant gay men in
      primary relationships.
AB  - We investigated differences in unprotected anal intercourse among gay men in HIV
      concordant and discordant primary relationships. Individuals were recruited in
      1992 from household- and bar-based samples of gay/bisexual men in Portland,
      Oregon, and Tucson, Arizona. Respondents were men who reported that they were in
      primary relationships of > or = 1 month and who reported their own and their
      partner's HIV status (n = 785). Comparisons were made between three groups: (a)
      HIV + respondents/HIV + partners; (b) HIV- respondents/HIV- partners; and (c)
      respondents whose partner's HIV status was different from their own (discordant),
      on sexual behavior, psychosocial, and demographic variables. Men in HIV
      concordant relationships reported significantly higher rates of unprotected anal
      intercourse (54% for +2 and 48% for --) than discordant couples (17%). HIV- men
      in concordant relationships were more likely to be monogamous (58%) and younger
      (22% < or = 25 years) than the other two groups. There were no significant
      differences among the groups regarding the kind of sexual behaviors they engaged
      in with nonprimary partners. The substantially lower rate of unprotected anal
      intercourse among men in discordant relationships compared to men in concordant
      relationships suggests that individuals and couples make judgments about sex and
      behavior based on knowledge of one's own and one's partner's HIV status.

PMID- 8989215
TI  - Changes in HIV-1 RNA plasma level in patients treated with foscarnet.

PMID- 8989216
TI  - HCV and HIV-related non-Hodgkin's lymphoma.

PMID- 8989217
TI  - Triple HIV-1 infection with group O and Group M of different clades in a single
      Cameroonian AIDS patient.

PMID- 8989218
TI  - T lymphocyte subset values among healthy Cameroonians.

PMID- 8989219
TI  - Autopsy findings in HIV-1-infected adults in Kenya.

PMID- 8989220
TI  - Probability of heterosexual transmission of HIV.

PMID- 8989221
TI  - Clinical review 85: Emerging issues in androgen replacement therapy.

PMID- 8989222
TI  - Epithelial cell thyroid cancer and thyroid stimulating hormone--when less is
      more.

PMID- 8989223
TI  - Treatment of scan-negative, thyroglobulin-positive metastatic thyroid cancer
      using radioiodine 131I and recombinant human thyroid stimulating hormone.

PMID- 8989224
TI  - Depot somatostatin analogs--a new first line therapy for acromegaly.

PMID- 8989225
TI  - Three year follow-up of acromegalic patients treated with intramuscular slow
      release lanreotide.
AB  - Somatostatin analogs are an alternative treatment to pituitary surgery and
      radiotherapy in acromegalic patients. Recently, a depot long-lasting formulation
      of slow release (SR) lanreotide has been shown to be effective in the short-term
      control of GH hypersecretion in acromegalic patients. We report the long-term
      follow-up of a cohort of 22 acromegalic patients treated with SR lanreotide
      during 1-3 yr. Thirteen females and 9 males, age 51 +/- 3 yr, presented with
      macroadenomas (n = 12), microadenomas (n = 8), or empty sella (n = 2). Seven
      patients previously had undergone a partial surgical removal of their adenomas,
      and 21 of them had mean plasma GH levels less than 5 micrograms/L during a
      previous octreotide treatment. According to GH values recorded after 3 months of
      twice monthly 30 mg SR lanreotide im injection, SR lanreotide was administered
      every 14 days (n = 13) or every 10 days (n = 9). At the 6-month visit, mean GH
      values were 5 micrograms/L or less in 68% and 2.5 micrograms/L or less in 27% of
      patients, and these results remained unchanged during the 1-3 yr follow-up
      period. During SR lanreotide treatment, the mean insulin-like growth factor I
      (IGF-I) concentrations remained in the normal range in 63% of patients. No escape
      from the treatment occurred in any of the cases. A significant decrease of the
      pituitary tumor volume was observed in 3 (13%) patients. The main side effect
      consisted of minor digestive problems during 48 h after each injection and was
      reported by 13 patients. Biannual gallbladder echographies revealed the
      occurrence of gallstones in 4 (18%) patients. In conclusion, these data confirm
      the efficacy and the tolerance of the long-term SR lanreotide administration (30
      mg im every 10-14 days) in the control of acromegaly.

PMID- 8989226
TI  - Sandostatin LAR in acromegalic patients: long-term treatment.
AB  - We have evaluated the long term effects and safety of Sandostatin LAR, a long
      acting formulation of octreotide, during 18 subsequent injections given every
      fourth week to 14 octreotide-sensitive acromegalic patients. The dosages (20, 30,
      or 40 mg) were adjusted according to GH response, side-effects, or symptom relief
      and assessed on day 28 after each injection. We found a stable and consistent
      suppression of GH and insulin-like growth factor (IGF-I) during the entire study
      period. Daily mean GH levels were suppressed below 2 micrograms/L in 9, to
      between 2-5 micrograms/L in 3, and to between 5-10 micrograms/L in 2 patients.
      The corresponding IGF-I values were suppressed to below 500 micrograms/L in 9
      patients and to between 500-1000 micrograms/L in the remaining 5 patients.
      Increasing the dosage of Sandostatin LAR from 20 to 30 mg had no obvious
      additional effect on GH suppression, but provided a further decrease in IGF-I
      levels. Forty milligrams of the drug had no additional effect on GH or IGF-I
      compared to 30 mg. Acromegalic signs and symptoms improved during treatment.
      Although the fluctuations of daily mean octreotide levels were high, dosage
      increments caused an increase in the average serum concentration in the
      individual patient. Pituitary tumor size reduction was seen in all previously
      untreated patients (n = 4). We found only minor changes in glucose metabolism
      (oral glucose tolerance test and hemoglobin A1C) during treatment, but no
      biologically relevant changes in thyroid function (TSH, T3, and free T4). One
      patient developed asymptomatic gallstones, and another acquired vitamin B12
      deficiency during treatment. The drug is well tolerated during long term
      treatment. Sandostatin LAR may well be the future medical treatment of choice for
      acromegalic patients.

PMID- 8989227
TI  - Idiopathic hypercalciuria and osteoporosis--distinct clinical manifestations of
      increased cytokine-induced bone resorption?

PMID- 8989228
TI  - Low bone mineral density and peripheral blood monocyte activation profile in
      calcium stone formers with idiopathic hypercalciuria.
AB  - Calcium stone formers (CaSF) with idiopathic hypercalciuria (IH) have been shown
      to have decreased bone mineral density (BMD). The mechanism of their bone loss
      remains obscure. Monokines like interleukin-1 beta (IL-1 beta), IL-6, tumor
      necrosis factor-alpha (TNF-alpha), and granulocyte macrophage stimulating factor
      (GM-CSF) are involved in bone remodeling, but only IL-1 excess has been
      incriminated in the bone loss of CaSF with IH. Therefore, to more precisely
      delineate the role of monocyte activation in the pathogenesis of bone loss in
      these patients, we studied the production of IL-1 beta, IL-6, TNF-alpha, and GM
      CSF by unstimulated or lipopolysaccharide (LPS)-stimulated cultured peripheral
      blood monocytes in 15 CaSF with IH, in 10 CaSF with dietary calcium-dependent
      hypercalciuria (DH), and in 10 healthy controls (C). Cytokines were measured in
      the culture medium by sensitive enzyme-linked immunosorbent assay and vertebral
      BMD by single energy computed tomography. The decrease of vertebral BMD in IH
      compared with DH, was confirmed (Z score: -1.2 +/- 0.2 vs. -0.5 +/- 0.2; P =
      0.04; Mann-Whitney). In the supernatant of unstimulated peripheral blood
      monocytes, IL-1 beta and TNF-alpha levels were higher in IH than in C
      (respectively, 40 +/- 21 vs. 7 +/- 1 pg/mL, P = 0.008 and 236 +/- 136 vs. 39 +/-
      23 pg/mL, P = 0.03); those of GM-CSF were greater in IH than in DH and C
      (respectively, 52 +/- 27 vs. 6 +/- 2, P = 0.04 and 6 +/- 2 pg/mL, P = 0.01) and
      those of IL-6 were not significantly different among the groups. After in vitro
      stimulation by LPS (10 micrograms/mL), the levels of the various monokines were
      not significantly different. In IH patients, the post-LPS levels of IL-6 were
      negatively correlated to vertebral BMD (n = 15, Z = -1.97, P = 0.04; Spearman),
      whereas those of GM-CSF were positively related to vertebral BMD (n = 15, Z =
      2.01, P = 0.04). In this study, calcium stone formers with IH have bone mineral
      decrease and a particular profile of peripheral blood monocytes activation. This
      latter is characterized by a spontaneously increased synthesis of IL-1 beta, TNF
      alpha, and GM-CSF. Furthermore, post-LPS levels of IL-6 and GM-CSF are correlated
      with vertebral BMD. These results suggest that monocyte activation may be
      involved in the bone loss of calcium stone formers with IH.

PMID- 8989229
TI  - C cell hyperplasia/neoplasia.

PMID- 8989230
TI  - Sex-related C cell hyperplasia in the normal human thyroid: a quantitative
      autopsy study.
AB  - We report a prospective quantitative image analysis study of C cells in 57 normal
      autopsy thyroid glands, serially sectioned and wholly embedded in paraffin; all
      slides were immunohistochemically stained for calcitonin. Computerized
      quantitative image analysis was performed on 47 cases to measure C cell surface
      area and parenchymatous surface area after immunoperoxidase staining for
      calcitonin. The method was time-effective, with a good reproducibility. C cells
      were mainly found in the middle third of each lobe. Important inter-individual
      variations were observed; the maximum C cell surface area in a section (Amax)
      ranged from 28 x 10(3) to 470 x 10(3) microns2 (mean, 167 x 10(3) microns2) among
      42 adults. Of particular interest was the important difference observed between
      sexes; Amax was twice as high in men (mean, 201 x 10(3) microns2) as in women
      (mean, 91 x 10(3) microns2; P = 0.0009). Moreover, 14 (33%) adult subjects [2
      women (15%) and 12 men (41%)] fulfilled C cell hyperplasia criteria, i.e. at
      least 3 fields at x 100 magnification containing more than 50 C cells, suggesting
      that a substantial part of the normal adult population could have C cell
      hyperplasia.

PMID- 8989231
TI  - 17 alpha-Hydroxylase deficiency: 1963-1966.

PMID- 8989233
TI  - Bone mineral density in children and adolescents: relation to puberty, calcium
      intake, and physical activity.
AB  - The association of height, weight, pubertal stage, calcium intake, and physical
      activity with bone mineral density (BMD) was evaluated in 500 children and
      adolescents (205 boys and 295 girls), aged 4-20 yr. The BMD (grams per cm2) of
      lumbar spine and total body was measured with dual energy x-ray absorptiometry.
      Lumbar spine volumetric BMD was calculated to correct for bone size. BMD and
      volumetric BMD increased with age. During puberty, the age-dependent increment
      was higher. After adjustment for age, the Tanner stage was significantly
      associated with all three BMD variables in girls and with spinal BMD in boys. In
      boys, positive correlations were found between BMD and both calcium intake and
      physical activity after adjustment for age. Stepwise regression analysis with
      weight, height, Tanner stage, calcium intake, and physical activity as
      determinants with adjustment for age resulted in a model with Tanner stage in
      girls and weight in boys for all three BMD variables. The major independent
      determinant of BMD was the Tanner stage in girls and weight in boys.

PMID- 8989232
TI  - Heterogeneity in clinical manifestation of autosomal dominant neurohypophyseal
      diabetes insipidus caused by a mutation encoding Ala-1-->Val in the signal
      peptide of the arginine vasopressin/neurophysin II/copeptin precursor.
AB  - Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a familial form
      of diabetes insipidus due to progressive vasopressin deficiency with onset
      typically at 1-6 yr of age. Affected individuals demonstrate specific
      degeneration of the vasopressinergic magnocellular neurons in the hypothalamic
      supraoptic and paraventricular nuclei and loss of the posterior pituitary bright
      spot on magnetic resonance imaging. The genetic locus of ADNDI is the arginine
      vasopressin-neurophysin II (AVP-NPII) gene. Mutations that cause ADNDI have been
      found to occur both within the signal peptide of the prepro-AVP-NPII precursor
      and within the coding sequence for neurophysin II, but not within the coding
      sequence for AVP itself. We evaluated the AVP-NPII genes in two independent
      families with ADNDI and identified a mutation (C280-->T) in the coding sequence
      for the signal peptide of the prepro-AVP-NPII precursor in both families. This
      mutation encodes an Ala-->Val substitution at the C-terminus of the signal
      peptide (-1 amino acid). This mutation predicts the complete inability of signal
      peptidase to cleave the signal peptide from the preproprecursor and supports the
      hypothesis that the progressive neural degeneration that underlies ADNDI is
      caused by accumulation of malprocessed precursor. However, considerable
      heterogeneity in the age of onset (1-28 yr of age) and the severity of diabetes
      insipidus among affected members of these two families suggests that additional
      factors modulate the rate and extent of progression of the neurodegeneration that
      results from this one specific ADNDI mutation.

PMID- 8989234
TI  - In vivo increase in beta-adrenergic lipolytic response in subcutaneous adipose
      tissue of obese subjects submitted to a hypocaloric diet.
AB  - The effects of 28 days of a very low calorie diet (382 Cal/day)) on the beta
      adrenergic lipolytic response and nutritive blood flow in sc adipose tissue were
      investigated in vivo using the microdialysis technique in 24 obese subjects. The
      diet did not modify the extracellular glycerol concentrations, but increased the
      local nutritive blood flow (measured by the ethanol escape method). The lipolytic
      response and the vasodilating effect of increasing concentrations of isoprenaline
      (from 0.001-10 mumol/L) added to the perfusate were enhanced after 28 days of
      diet. Before the diet, equimolar concentrations (100 mumol/L) of dobutamine
      [selective beta 1-adrenoceptor (beta 1-AR) agonist], terbutaline (selective beta
      2-AR agonist), and CGP 12,177 (selective beta 3-AR agonist) increased glycerol
      concentration in adipose tissue. The lipolytic effect of terbutaline was the
      greatest, and the effect of CGP 12,177 was the least marked. After 28 days of the
      diet, the effects of terbutaline and CGP 12,177 were not modified, whereas the
      effect of dobutamine was increased and reached the effect of terbutaline. The
      three agonists increased nutritive blood flow; this effect was not modified
      during the diet. In summary, this study demonstrates an increase in the in vivo
      lipolytic responses to isoprenaline and dobutamine during the hypocaloric diet.
      Furthermore, functional beta 3-AR are present in the sc adipose tissue of obese
      patients; however, their activation is only weakly involved in the lipolytic
      process in this population and is not modified by the hypocaloric diet.

PMID- 8989235
TI  - Alternatively spliced transcripts of the aromatase cytochrome P450 (CYP19) gene
      in adipose tissue of women.
AB  - Estrogen biosynthesis in adipose tissue has assumed great significance in terms
      of a number of estrogen-related diseases. The biosynthesis of estrogens from C19
      steroids is catalyzed by a specific form of cytochrome P450, namely aromatase
      cytochrome P450 (P450arom; the product of the CYP19 gene). The human CYP19 gene
      comprises nine coding exons, II-X, and its transcripts are expressed in the
      ovary, placenta, testes, adipose tissue, and brain. Tissue-specific expression of
      the CYP19 gene is determined at least in part by the use of tissue-specific
      promoters, which give rise to transcripts with unique 5'-noncoding termini. Thus,
      the distal promoter I.1 is responsible for expression uniquely in placenta. On
      the other hand, the proximal promoter II, which regulates expression via a cAMP
      dependent signaling pathway, is responsible for expression in the gonads.
      Transcripts in breast adipose tissue contain 5'-termini corresponding to
      expression derived from promoters I.4, II, and I.3, with I.4-specific termini
      predominating. The latter are derived from promoter I.4, which contains a
      glucocorticoid response element and an interferon-gamma activation site element
      and is responsible for expression in the presence of glucocorticoids and members
      of the class I cytokine family. The object of the present study was to determine
      the distribution of these various transcripts in adipose tissue from abdomen,
      buttocks, and thighs of women, as this would provide important clues to the
      factors regulating aromatase expression in these sites. To achieve this, we
      employed competitive reverse transcription-PCR to amplify unique 5'-ends of each
      of the transcripts of the CYP19 gene that are expressed in adipose tissue as well
      as for the coding region to evaluate total CYP19 gene (P450arom) transcript
      levels. We observed that exon I.4-specific transcripts were predominantly present
      in adipose tissue samples obtained from women regardless of the tissue site or
      the age of the individual. In these tissues, promoter II- and exon I.3-specific
      transcripts were present in lower copy numbers. We also demonstrated that in
      these sites total or exon-specific P450arom transcripts levels increased in
      direct proportion to advancing age and that transcript levels were the highest in
      buttocks, followed by thighs, and lowest in the abdomen. These results suggest
      that in normal human adipose tissue, aromatase expression is mainly under local
      control by a number of cytokines via paracrine and autocrine mechanisms in the
      presence of systemic glucocorticoids.

PMID- 8989236
TI  - Methylprednisolone exposure, rather than dose, predicts adrenal suppression and
      growth inhibition in children with liver and renal transplants.
AB  - Some patients receiving glucocorticoids develop adverse effects even with very
      low doses, whereas others fail to achieve the desired effects with the usual
      therapeutic doses. We hypothesized that glucocorticoid exposure, rather than the
      dose, would predict the development of adverse effects in children receiving long
      term glucocorticoid treatment. Sixteen liver and 10 renal transplant recipients
      on triple immunosuppression were studied. Serum total methylprednisolone (MP) and
      cortisol were determined before and up to 10 h after peroral MP administration.
      Heights were recorded 6 months before and after the study day. The MP dose (in
      milligrams per kilogram) was not correlated with the serum cortisol concentration
      or with the change in height SD score. The area under the serum MP time vs.
      concentration curve was inversely related to the serum cortisol concentration and
      to the height SD score, and was the best predictor of both adrenal function and
      growth. Dosing according to area under the serum MP time vs. concentration curve
      in children receiving long-term glucocorticoid treatment may substantially reduce
      the incidence of adverse effects without affecting therapeutic efficacy.

PMID- 8989237
TI  - Serum interleukin-6 and bone metabolism in patients with thyroid function
      disorders.
AB  - To determine the possible involvement of interleukin-6 (IL-6) in the bone loss of
      hyperthyroidism, relationships between thyroid status, biochemical and
      densitometric parameters of bone metabolism, and IL-6 were studied in female
      subjects. Patients with hyperthyroidism caused by either toxic nodular goiter or
      Graves' disease had significantly higher serum IL-6 concentrations than normal
      controls. Within the control group, serum IL-6 was higher in postmenopausal than
      in premenopausal women, but this influence of menopausal status was not seen in
      the hyperthyroid patients. The production of IL-6 by blood mononuclear cells was
      higher in cells from the hyperthyroid women. Bone turnover was increased in the
      hyperthyroid patients based on serum osteocalcin and urinary deoxypyridinoline
      excretion, and the hyperthyroid group also had reduced radius bone mineral
      content (BMC). A subgroup of hyperthyroid patients who had the lowest BMC (values
      more than 1 SD below normal age-matched controls) also had serum IL-6
      concentrations significantly greater than those of hyperthyroid patients showing
      less reduction of BMC. The correlations observed in this study support the
      possibility that IL-6 plays a role in mediating the bone loss that results from
      excess thyroid hormone.

PMID- 8989238
TI  - Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between
      childhood onset and adult onset before and during human GH treatment. Adult
      Growth Hormone Deficiency Study Group.
AB  - The onset of adult GH deficiency may be during either adulthood (AO) or childhood
      (CO), but potential differences have not previously been examined. In this study
      the baseline and GH therapy (12.5 micrograms/kg per day) data from CO (n = 74;
      mean age 29 yr) and AO (n = 99; mean age 44 yr) GH-deficient adult patients have
      been compared. The first 6 months comprised randomized, double-blind treatment
      with GH or placebo, then all patients were GH-treated for a further 12 months. At
      baseline the height, body weight, body mass index, lean body mass, and waist/hip
      ratio of AO patients were significantly (P < 0.001) greater than in CO patients.
      Serum insulin-like growth factor-I (IGF-I) levels were below normal but were
      lower in CO than AO patients (P < 0.001), and the correlation with IGF binding
      protein-3 was stronger in CO than in AO patients. Osteocalcin concentration in CO
      patients was above the normal range and significantly greater than in AO
      patients. Both groups had significant psychosocial distress, but the deviation
      from normality was greater in AO patients. Throughout GH therapy there was a
      significant increase in lean body mass and significant decrease in percent body
      fat and sum of skinfolds in each group. Wais/hip ratio was decreased by long-term
      therapy in AO but not CO patients. Total and low density lipoprotein cholesterol
      levels were decreased from baseline at 6 months in AO but not CO patients and
      high density lipoprotein cholesterol was increased in both groups throughout
      therapy. IGF-I and IGF binding protein-3 were increased into the normal range by
      GH therapy in both groups. Mean osteocalcin level in AO patients was increased at
      6 months with no further change with GH therapy, whereas in CO patients there was
      a steep increase up to 12 months but then a sharp decrease. Nottingham Health
      Profile scores showed significant improvements in physical mobility and energy at
      18 months of therapy in AO patients but no consistent effects in CO patients. GH
      induced side effects were mainly reported by AO patients; very few CO patients
      reported treatment-emergent adverse events. These results demonstrate significant
      differences in clinical and biochemical presentation and responses to therapy of
      the adult GH deficiency syndrome. This is consistent with the existence of two
      entities, developmental (CO) and metabolic (AO), and the different functions of
      GH at different periods of life.

PMID- 8989239
TI  - High expression of the POU factor Brn3a in aggressive neuroendocrine tumors.
AB  - A new family of POU transcription factors called Brn plays a role in development
      of the brain and some neuroendocrine structure. Because a member of this family,
      Brn3a, is present in the ACTH-producing mouse pituitary tumor AtT-20, binds to
      POMC promoter, and stimulates its activity, we studied its human homolog in ACTH
      secreting or nonsecreting tumors of pituitary and bronchial origins. A specific
      and quantitative reverse transcription-PCR assay was developed to assess Brn3a
      transcripts in tumor ribonucleic acid. Brn3a transcript levels were invariably
      low (< 5 x 10(-6) arbitrary units) in four GH-, two PRL-, three gonadotropin-,
      and seven of eight ACTH-producing pituitary adenomas. A single highly invasive
      ACTH-secreting pituitary adenoma in a patient who ultimately died with liver
      metastases, and the mouse corticotroph tumor cell line AtT-20 had high Brn3a
      transcripts levels at 3 x 10(-5) and 4 x 10(-4) arbitrary units, respectively.
      Five typical bronchial carcinoids had barely detectable levels (< 5 x 10(-6)
      arbitrary units), whereas seven of eight small cell carcinomas of the lung
      (SCCLs) had extremely high levels (between 10(-3)-10(-1) arbitrary units); six of
      seven atypical bronchial carcinoids had intermediate values, between 10(-6) and 5
      x 10(-3) arbitrary units. Although nine bronchial tumors produced POMC, there was
      no association between Brn3a levels and POMC gene expression; the two tumors with
      the highest POMC messenger ribonucleic acid contents were two bronchial
      carcinoids with barely detectable Brn3a levels. A gel mobility shift assay was
      performed with a rat CRH promoter probe that binds Brn3a; extracts of the POMC
      producing human SCCL line DMS-79, which contained high levels of Brn3a
      transcripts, generated the same specific complex as did AtT-20 cell extracts.
      These data show that Brn3a gene expression in neuroendocrine tumors is not
      correlated with POMC gene expression; rather, it is strikingly elevated in the
      highly aggressive tumors, independently of their POMC status and their pituitary
      or nonpituitary origin.

PMID- 8989240
TI  - Circulating adrenomedullin does not regulate systemic blood pressure but
      increases plasma prolactin after intravenous infusion in humans: a
      pharmacokinetic study.
AB  - Adrenomedullin has been proposed to be a circulating hormone regulating systemic
      and pulmonary blood pressure. A potential therapeutic role in the management of
      pulmonary hypertension has been suggested based on animal studies, but the
      pharmacokinetics and pharmacodynamics in human subjects have not been studied. We
      have infused adrenomedullin into volunteers at 3.2 pmol/kg.min, which more than
      quadrupled (52 pmol/L) normal circulating concentrations. At this dose no change
      in heart rate or blood pressure was noted. When infused at 13.4 pmol/kg.min to
      achieve a concentration over 40 times normal circulating levels (448 pmol/L),
      there was a significant fall in diastolic blood pressure from 69 +/- 2 to 53 +/-
      2 mm Hg and a significant increase in pulse rate from 57 +/- 3 to 95 +/- 4
      beats/min. Circulating PRL concentrations rose from 197 +/- 46 to 372 +/- 64 IU/L
      (mean +/- SEM; P < 0.01). No effect was seen on ACTH, TSH, FSH, LH, or cortisol.
      When the infusion was discontinued, baseline pulse and blood pressure were
      reestablished after 20 min. Adrenomedullin has a MCR of 27.4 +/- 3.6 mL/kg.min,
      with a circulating half life of 22 +/- 1.6 min and an apparent volume of
      distribution of 880 +/- 150 mL/kg. Column chromatography of plasma taken during
      infusion and decay of adrenomedullin showed no evidence of the production of
      additional molecular forms. These results are consistent with a peptide that is
      markedly tissue bound. Plasma adrenomedullin concentrations were increased in
      patients with renal impairment (14.1 +/- 0.9 pmol/L) compared to those in healthy
      volunteers (8.1 +/- 0.7 pmol/L), with a good correlation (r = 0.86) between
      circulating adrenomedullin and plasma creatinine. The circulating concentration
      of adrenomedullin necessary to affect blood pressure greatly exceeds that
      observed in healthy volunteers and in patients with a range of pathological
      conditions. Thus, adrenomedullin may be a paracrine regulator of vascular smooth
      muscle in humans.

PMID- 8989241
TI  - Intercellular adhesion molecule-1 is expressed on human granulosa cells and
      mediates their binding to lymphoid cells.
AB  - Some immune cellular components have been recently demonstrated to play a
      critical role in ovarian physiology. Resident ovarian white blood cells are known
      to produce cytokines that modulate granulosa cell (GC) functions and
      differentiation. Moreover, it has been postulated that, during the formation of
      the corpus luteum and luteolysis, human luteal cells are able to interact with
      lymphocytes and macrophages through some adhesion molecules. This study was
      designed to examine, at messenger RNA and protein levels, whether intercellular
      adhesion molecule (ICAM)-1, known to be involved in leukocyte-cell binding, is
      expressed by human GCs. Furthermore, we also investigated whether this molecule
      could be involved in the complex events that allow the interaction between the
      ovary and the immune system. GCs, obtained from women undergoing in vitro
      fertilization procedures, were enzymatically dispersed with collagenase and
      cultured for different time periods. To assess the presence of ICAM-1 messenger
      RNA, total RNA obtained from freshly aspirated GCs and GCs luteinized in culture
      was reverse transcribed and then amplified using two oligonucleotide primers
      specific for the human ICAM-1 gene. A single major DNA band of the expected size
      (943 bp) was obtained. The identity of this material with the human ICAM-1
      sequence was further confirmed by restriction enzyme analysis. Surface ICAM-1
      protein was detected by flow cytometric analysis on luteinized GCs cultured for 7
      and 15 days. Finally, to evaluate a possible functional activity of ICAM-1, a
      51Cr-release-binding assay between peripheral blood lymphocytes and luteinized
      GCs was performed in the presence and absence of a monoclonal antibody against
      ICAM-1. As a result, lymphocyte adhesion to GC monolayers was significantly, but
      not completely, inhibited by the anti-ICAM-1 monoclonal antibody. These findings
      demonstrate that intercellular interactions between GCs and the immune system
      are, at least in part, mediated by the adhesion molecule ICAM-1. Based on this
      data, we might speculate that this molecule could participate in the remodeling
      processes of the ovarian endocrine compartment.

PMID- 8989242
TI  - Cardiac abnormalities in patients with primary hyperparathyroidism: implications
      for follow-up.
AB  - Patients with primary hyperparathyroidism (PHPT) show a high incidence of left
      ventricular hypertrophy, cardiac calcific deposits in the myocardium, and/or
      aortic and mitral valve calcification and thus may carry an increased risk of
      death from circulatory diseases. This prospective study was designed to assess an
      effect of parathyroidectomy on cardiac abnormalities of patients with PHPT.
      Echocardiography was used to evaluate the mechanical performance of the heart
      muscle, the thickness of the left ventricular wall, myocardial calcific deposits,
      and valvular calcifications within 12 and 41 months after parathyroidectomy. In a
      blinded fashion, aortic and mitral value calcifications were determined in 46%
      and 39% of patients with PHPT. Calcific deposits in the myocardium were found in
      74% of patients. Follow-up studies after parathyroidectomy disclosed no evidence
      of progression of these calcifications. Before operation left ventricular
      hypertrophy was detected in 82%. After parathyroidectomy and 41 months of
      normocalcemia and normal PTH concentrations, a regression of hypertrophy of the
      interventricular septum and the posterior wall by -6% and -19% (P < 0.05) was
      observed. Subgroup analysis disclosed the most impressive long-term reduction of
      left ventricular hypertrophy in patients without a history of hypertension (-11%
      and -21%; P < 0.05 and P < 0.005); no changes were determined in 9 patients who
      developed secondary hyperparathyroidism after operation. The present data show a
      high incidence of left ventricular hypertrophy and aortic and/or mitral valve
      calcifications in patients with PHPT. Follow-up at 1 year and at 41 months after
      successful parathyroidectomy disclose regression of hypertrophy. Our results give
      evidence that parathyroid hormone per se plays an important role in the
      maintainance of myocardial hypertrophy. Post-surgical restoration of
      normocalcemia and normalization of parathyroid hormone valvular sclerosis
      persists without evidence of progression. We further conclude that patients with
      PHPT and parathyroidectomy are at low risk for the development of severe aortic
      and mitral valve stenosis within this period of time.

PMID- 8989243
TI  - Epidermal growth factor receptors in uteroplacental tissues in term pregnancy
      before and after the onset of labor.
AB  - Using saturation binding assays and Scatchard analyses, we determined the
      concentrations and binding affinities of epidermal growth factor (EGF) receptors
      in human myometrium (n = 13) and decidua (n = 10) before and during labor and in
      placenta (n = 15), chorion (n = 17), and amnion (n = 17) before labor, during
      labor, and after vaginal delivery. Each tissue was individually assayed. In
      myometrium and chorion, EGF receptors increased significantly from 5.6 +/- 0.8
      and 13.5 +/- 1.7 fmol/mg protein (mean +/- SEM) before labor to 11.1 +/- 2.8 and
      26.7 +/- 3.0 fmol/mg protein, respectively, after the onset of labor (P < 0.05).
      In amnion, EGF receptors increased from 12.8 +/- 2.7 fmol/mg protein before labor
      to 33.0 +/- 2.3 fmol/mg protein during labor, but decreased significantly (5.9 +/
      1.2 fmol/mg protein) with vaginal delivery (P < 0.05). Decidual and placental
      concentrations of EGF receptors did not change significantly with labor. The
      binding affinity of EGF receptors in all tissues studied did not change
      significantly with labor, as reflected by their respective association and
      dissociation constants. Up-regulation of EGF receptors in myometrium, chorion,
      and amnion with spontaneous labor may enhance stimulation of prostanoid
      production and stimulate uterine activity.

PMID- 8989244
TI  - Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in
      breast cancer patients with bone metastases.
AB  - 1,25-dihydroxyvitamin D (1,25-(OH)2D) stimulates differentiation and controls
      proliferation in breast cancer cells. The role of endogenous 1,25-(OH)2D and its
      relation to PTH related protein (PTHrP) during the progression of breast cancer
      is not known; we therefore investigated these hormones in two studies. In a cross
      sectional study of patients with breast cancer at different stages of disease,
      serum 1,25-(OH)2D levels (mean +/- SE) were highest in early disease (102 +/- 3.7
      pmol/L), fell in normocalemic patients with bone metastases (52 +/- 5.3 pmol/L; P
      < 0.01), and were lowest in hypercalcemic patients (33 +/- 5.6 pmol/L; P <
      0.001). PTHrP was detectable in the serum of only one normocalcemic patient with
      progressive metastases but was present in 11 of the 12 hypercalcemic patients,
      thus PTHrP did not stimulate 1,25-(OH)2D synthesis. In a 6-month longitudinal
      study of normocalcemic patients with bone metastases undergoing hormonal therapy,
      serum 1,25-(OH)2D concentrations fell in patients whose disease progressed (P =
      0.0056), but remained constant in those who were stable or responded to
      treatment. These changes in 1,25-(OH)2D preceded clinical signs of progression
      and predicted disease response. In the progressive group, five of whom died
      during the study, 1,25-(OH)2D decreased between the initial and final samples,
      PTH fell significantly from 24.8 to 13.5 ng/L (P = 0.025), serum calcium rose
      from 2.27 to 2.39 mmol/L (P = 0.017), and the urinary calcium/creatinine ratio
      rose from 0.37 to 0.68 (P = 0.046). PTH and 1,25-(OH)2D were significantly
      correlated in the final samples from this group, Spearman's rank correlation =
      0.80, P = 0.022. The results indicate that normocalcemia in these patients is
      maintained, at the expense of suppressing PTH and 1,25-(OH)2D, in the face of
      increased calcium released from lytic lesions in bone. Loss of the
      antiproliferative effects of 1,25-(OH)2D may then permit more rapid secondary
      growth of the tumor.

PMID- 8989245
TI  - Abdominal fat determines growth hormone-binding protein levels in healthy
      nonobese adults.
AB  - The circulating high affinity GH-binding protein (GHBP), which derives from the
      extracellular domain of the hepatic GH receptor, correlates inversely to GH
      levels and directly to body mass index (BMI) in healthy adults. As GH secretion
      and adiposity are also interrelated, we tested the hypothesis that body
      composition more than GH, determines GHBP levels in healthy adults. Forty-two
      healthy adults [21 females and 21 males; mean age, 39.4 yr range, 27-59 yr); mean
      BMI, 23.9 kg/m2 (range, 18.9-34.7 kg/m2)], underwent anthropometric measurements
      (BMI, W/H ratio, computed tomography scan, dual energy x-ray absortiometry (DEXA)
      scan, and bioimpedance) in addition to two GH stimulation tests (arginine and
      clonidine) and a 24-h GH profile. By simple linear regression, serum GHBP
      correlated positively to several indices of adiposity: intraabdominal fat (r =
      0.537; P = 0.001), sc abdominal fat (r = 0.680; P < 0.001), BMI (r = 0.483; P =
      0.001), W/H ratio (r = 0.452; P = 0.003), total body fat (DEXA scanning; r =
      0.503; P = 0.002), and body fat (bioimpedance; r = 0.354; P = 0.023). Lean body
      mass estimated by DEXA scan was negatively associated with GHBP (r = 0.541; P <
      0.001). GHBP was inversely proportional to arginine-stimulated GH release (r = 
      0.346; P = 0.027) and negatively associated with several measures of spontaneous
      GH release as estimated by deconvolution analysis (GH mass, GH production rate,
      and mean GH; r = -0.371; P = 0.017, r = -0.393; P = 0.011, and r = -0.343; P =
      0.028, respectively)). With multiple linear regression analyses, indices of
      adiposity were significant determinants of GHBP levels, whereas GH status did not
      contribute independently to the prediction of GHBP. Neither insulin-like growth
      factor I nor fasting insulin levels correlated to GHBP levels. In conclusion,
      GHBP levels in normal adults seem to be determined by abdominal fat mass rather
      than GH secretion.

PMID- 8989246
TI  - A low starting dose of genotropin in growth hormone-deficient adults.
AB  - We investigated the effect of 12 weeks of recombinant human GH therapy given in
      three different doses on serum insulin-like growth factor I (IGF-I) and IGF
      binding protein-3 (IGFBP-3) in patients with GH deficiency (GHD). We used low
      doses of recombinant human GH (Genotropin), as we and others recently found a
      strong decrease in physiological GH production with age in healthy controls,
      especially in those older than 30 yr. Sixty patients with GHD (aged 20-70 yr)
      were randomized to one of the three dose groups. Group 1 used a dose of 0.6
      IU/day for 12 weeks. Group 2 started at a dose of 0.6 IU for 4 weeks followed by
      1.2 IU/day for 8 weeks. Group 3 used 0.6 IU for 4 weeks, followed by 1.2 IU/day
      for 4 weeks and 1.8 IU/day thereafter. IGF-I concentrations (nanomoles per L)
      were determined by RIA after extraction and purification on ODS-silica columns.
      The measurement of IGFBP-3 (milligrams per L) was performed by RIA. The three
      groups were equal with regard to age, sex and body mass index. At the start of
      the study, we found lower levels of both serum IGF-I and IGFBP-3 in childhood
      onset GHD than in adult-onset GHD. Moreover, there was a gender difference;
      female GHD patients had lower serum IGF-I levels than male patients. Serum IGF-I
      levels were low in both childhood-onset and adult-onset GHD. Serum IGFBP-3
      levels, however, were low in patients with childhood-onset GHD, but normal in
      patients with adult-onset GHD. After 12 weeks of treatment, IGF-I levels were low
      normal in the low dose group and normal in groups 2 and 3 of both adult-onset and
      childhood-onset GHD. In adult-onset GHD, serum IGFBP-3 increased to high normal
      levels in all groups, whereas it increased to low normal levels in childhood
      onset GHD. This study demonstrates differences in the biochemical characteristics
      of childhood-onset and adult-onset GHD. In patients with adult-onset GHD, serum
      IGFBP-3 levels are not significantly decreased and, therefore, cannot be used as
      a screening method for GHD or as a dose-finding parameter. GH therapy at doses of
      0.6 and 1.2 IU/day in male and female patients, respectively, is, in general,
      able to increase serum IGF-I into the normal range after 12 weeks of treatment,
      without reaching supranormal levels of serum IGF-I. This dose could, therefore,
      be a starting dose in GH-deficient adults.

PMID- 8989247
TI  - Characterization of integrin expression in a well differentiated endometrial
      adenocarcinoma cell line (Ishikawa).
AB  - The pattern of constitutive and cycle-dependent integrins in normal endometrium
      has recently been established, suggesting a role for cell adhesion molecules in
      endometrial receptivity and implantation. Currently few, if any, models exist for
      the study of human endometrial integrins and their role in establishment of the
      receptive endometrial phenotype. The Ishikawa cell line maintains functional
      estrogen receptors and progesterone receptors. The progesterone receptors in
      these cells are inducible by priming with estradiol and down-regulated by
      treatment with progesterone. In the present study the pattern of integrin
      expression in this well differentiated endometrial cell line is compared to that
      in normal endometrial epithelium using immunohistochemistry and flow cytometry
      and is confirmed by immunoprecipitation, Western immunoblot, and PCR. Like normal
      endometrial epithelium, Ishikawa cells maintain constitutive expression of alpha
      2 beta 1, alpha 3 beta 1, alpha 6 beta 4. PCR demonstrates the expected size
      fragments of each, although evidence for alternatively spliced forms of the alpha
      2-subunit was noted. Progesterone treatment of estradiol-primed cells resulted in
      increased expression of the alpha 1 beta 1 collagen-laminin receptor and
      suppression of the alpha v beta 3 vitronectin receptor, two of the cycle
      dependent integrins expressed by normal endometrial epithelium. These data
      support the use of Ishikawa cells as an excellent model to study the regulation
      endometrial integrins and advance our understanding of hormonally mediated events
      surrounding implantation.

PMID- 8989248
TI  - CTLA4 alanine-17 confers genetic susceptibility to Graves' disease and to type 1
      diabetes mellitus.
AB  - The genetic susceptibility to Graves' disease and type 1 (insulin-dependent)
      diabetes mellitus is conferred by genes in the human leukocyte antigen region on
      the short arm of chromosome 6, but several other genes are presumed to determine
      disease susceptibility. Among those candidate genes is the cytotoxic T lymphocyte
      antigen 4 (CTLA4) located on chromosome 2q33 in man. We investigated the
      distribution of the CTLA4 exon 1 polymorphism (49 A/G) in Graves' disease and
      IDDM. This dimorphism at codon 17 results in an amino acid exchange (Thr/Ala) in
      the leader peptide of the expressed protein and was analyzed by PCR, single
      strand conformation polymorphism, and restriction fragment length polymorphism
      analysis in 305 patients with Graves' disease, 293 patients with IDDM, and 325
      controls. Patients with Graves' disease had significantly more Ala alleles than
      controls, both as homozygotes (21% vs. 13%) and as heterozygotes (53% vs. 46%),
      and less Thr as homozygotes (26% vs. 42%; P < 2 x 10(-4). The phenotypic
      frequency of Ala-positive patients (73%) was significantly higher than of
      controls (58%; P = 10(-4); relative risk = 2). Patients with IDDM also had
      significantly more Ala alleles as homozygotes (19%) or heterozygotes (50%; P =
      0.01). In conclusion, an alanine at codon 17 of CTLA4 is associated with genetic
      susceptibility to Graves' disease as well as to IDDM.

PMID- 8989249
TI  - Autoantibodies against aromatic L-amino acid decarboxylase in autoimmune
      polyendocrine syndrome type I.
AB  - Patients with autoimmune polyendocrine syndrome type I (APS I) have
      autoantibodies against the enzyme aromatic L-amino acid decarboxylase (AADC) of
      pancreatic beta-cells. The aim of the present study was to investigate the
      presence of anti-AADC antibodies in a large cohort of patients with APS I, and in
      patients with isolated insulin-dependent diabetes mellitus (IDDM). We found
      autoantibodies against AADC in 35 of 69 patients (51%) with APS I but in none of
      138 patients with isolated IDDM or 91 healthy controls. Among the patients with
      APS I, anti-AADC antibodies were more often found in those with hepatitis (11/12,
      92%), than in those without hepatitis (24/57, 42%) (P = 0.003). Similarly, of 15
      patients with vitiligo, 12 (80%) had anti-AADC antibodies, compared with 23/54
      (43%) without vitiligo (P = 0.021). Of the 9 APS I patients with IDDM, 5 had
      antibodies against both AADC and glutamate decarboxylase, 2 against AADC only,
      and 2 against glutamate decarboxylase only. Interestingly, AADC is present in
      relatively large amounts in the liver, where its function is unknown. Thus, an
      autoimmune reactivity against AADC may be involved in the pathogenesis of
      autoimmune chronic active hepatitis and vitiligo in APS I patients, whereas the
      role of AADC in the development of IDDM in these patients remains to be
      determined.

PMID- 8989250
TI  - Urinary free cortisol and cortisone determined by high performance liquid
      chromatography in the diagnosis of Cushing's syndrome.
AB  - To determine the efficacy of cortisol and its metabolite, cortisone, measured
      simultaneously by high performance liquid chromatography (HPLC) in the diagnosis
      of Cushing's syndrome, we retrospectively reviewed the histories of 29 surgically
      proven Cushing's syndrome patients (20 Cushing's disease, 5 ectopic ACTH
      syndrome, and 4 adrenal Cushing's syndrome) and 6 patients with exogenous
      Cushing's syndrome. These 35 patients had urinary free cortisol determined by
      both HPLC and competitive binding methods. The efficacy of the HPLC assay using
      cortisol alone was equivalent to that of the competitive binding assay; 22 of 29
      (76%) patients had increased cortisol. Cortisone also aided in the diagnosis; 25
      of 29 (86%) had increased cortisone. Twenty-seven of the 29 (93%) patients had
      either both cortisone and cortisol (n = 19) or at least 1 of the 2 (n = 8)
      increased. All 6 patients with exogenous Cushing's syndrome had suppressed
      urinary free cortisol, cortisone, and the presence of prednisone and
      prednisolone. In the competitive binding assay, all exogenous Cushing's patients
      had falsely increased cortisol results. In conclusion, urinary free cortisol plus
      cortisone determined simultaneously by HPLC added a new dimension to the
      diagnosis of Cushing's syndrome. It should be considered when exogenous Cushing's
      syndrome is suspected or when only one urinary cortisol test is allowed to be
      ordered.

PMID- 8989251
TI  - High ratios of free to total insulin-like growth factor-I in early infancy.
AB  - Insulin-like growth factor-I (IGF-I) is a major effector of somatic growth and
      metabolism. In normal, nonpregnant plasma, most of the IGF-I is complexed to
      specific IGF-binding proteins (IGFBPs), particularly IGFBP-3; only a minor
      fraction of plasma IGF-I exists in a free form. Recently, we have reported that
      free IGF-I levels, as measured using a new immunoradiometric assay, are
      relatively high in maternal plasma during pregnancy because of increased IGFBP-3
      proteolytic activity. These high free IGF-I levels are physiologically important
      for the growth of maternal tissues such as uterus and placenta, which are related
      to the fetal growth. Growth during early infancy may be a continuation of fetal
      growth. In the present study, we have analyzed free and total plasma IGF-I and
      IGFBP-3 proteolytic activity in early infancy. Although the levels of free and
      total IGF-I were not significantly different in early infancy as compared with
      prepubertal periods, the ratio of free to total IGF-I (mean = 2.04%) was
      relatively increased and was similar to the ratio in pregnancy plasma (1.86%).
      However, unlike in maternal plasma, the high ratios were not totally caused by
      increased IGFBP-3 proteolytic activity. Our results suggest that there may be an
      increased conversion of plasma IGF-I to a free form in early infancy. The
      resultant increase in IGF-I bioavailability could contribute to the rapid somatic
      growth in early infancy.

PMID- 8989252
TI  - Catecholamine-induced adipocyte lipolysis in human hyperthyroidism.
AB  - Increased lipid mobilization in thyrotoxicosis is attributed to amplification of
      catecholamine action in fat cells by thyroid hormones. We investigated the
      adrenergic regulation of lipolysis in isolated sc abdominal fat cells obtained
      from 14 patients with thyrotoxicosis and 18 control subjects. Ten of the
      hyperthyroid subjects were also reinvestigated after antithyroid treatment. The
      thyrotoxic state was associated with a 3-fold increase in maximum norepinephrine
      induced lipolysis (P < 0.005), unaltered sensitivity to dobutamine (selective
      beta 1-adrenoceptor agonist) and clonidine (selective alpha 2-adrenoceptor
      agonist), but 15 times enhanced sensitivity to terbutaline (selective beta 2
      adrenoceptor agonist; P < 0.01). Moreover, thyrotoxicosis was accompanied by a 3
      fold increase in beta 2-adrenoceptor number (P < 0.005), but unchanged beta 1
      adrenoceptor levels. Further, the lipolytic effects of dibutyryl cAMP (activating
      protein kinase A and thereby hormone-sensitive lipase) and forskolin (activating
      adenylate cyclase) were about 60% enhanced (P < 0.005). No change in the maximum
      activity of the hormone-sensitive lipase could be demonstrated in the
      hyperthyroid state compared to that in the euthyroid state. The observed
      abnormalities in lipolysis and beta 2-adrenoceptor number were normalized after
      antithyroid treatment. It is concluded that in human hyperthyroidism, the
      interactions between thyroid hormone and catecholamines in adipocytes involve
      abnormalities at both receptor and postreceptor levels. The former mechanism
      seems to be a selective increase in the expression of the beta 2-adrenoceptors.
      The latter mechanism involves increased ability of cAMP to activate hormone
      sensitive lipase, but not a change in maximum enzyme capacity.

PMID- 8989253
TI  - Lysyl oxidase (ras recision gene) expression in human amnion: ontogeny and
      cellular localization.
AB  - The tensile strength of human fetal membranes is attributable to interstitial
      collagens of the zona compacta of the avascular amnion. Collagen fiber strength
      and proteolytic resistance is provided by inter and intramolecular cross-links of
      collagen fibrils, which are formed in a series of reactions initiated by lysyl
      oxidase. Lysyl oxidase activity in amnion tissues varied by more than 400-fold in
      a highly significant inverse manner as a function of gestational age (12-43
      weeks). At 12-14 weeks gestation, the levels of lysyl oxidase messenger
      ribonucleic acid, protein, and activity in amnion are very high. During the
      second trimester of pregnancy, however, these decline abruptly, and a nadir is
      reached at about 20-24 weeks gestation, which persists to term. The level of
      lysyl oxidase messenger ribonucleic acid was greater in amnion mesenchymal cells
      than in amnion epithelial cells. The decline in lysyl oxidase in amnion may be
      attributable to a correspondent decline in the density of amnion mesenchymal
      cells with fetal development.

PMID- 8989254
TI  - Effects of estradiol and medroxyprogesterone-acetate treatment on erythrocyte
      antioxidant enzyme activities and malondialdehyde plasma levels in amenorrhoic
      women.
AB  - Plasma levels of 17 beta-estradiol (E2) and malondialdehyde and erythrocyte
      antioxidant enzyme [superoxide dismutase, catalase, and glutathione-peroxidase
      (GSH-Px)] activities were evaluated in 20 healthy eumenorrhoic women (EW) on day
      7 of the menstrual cycle and in 48 secondary hypothalamic amenorrhea patients
      (AP) (time 0). The AP were randomly divided into four subgroups of 12 subjects
      and treated with transdermal E2 for 30 days (subgroup A), oral
      medroxyprogesterone-acetate for 30 days (subgroup B), and transdermal E2 plus
      medroxyprogesterone-acetate for 30 days (subgroup C). The fourth subgroup acted
      as control. E2 and malondialdehyde plasma levels and superoxide dismutase,
      catalase, and GSH-Px activities were evaluated in subgroups A, B, and C on day 30
      of therapy and in the control subgroup. GSH-Px activity was significantly higher
      in EW than in AP at time 0. A statistically significant increase in E2 plasma
      levels and GSH-Px activity was observed in subgroups A and C on day 30 of
      treatment, and there was a significant positive correlation between E2 plasma
      levels and GSH-Px activity in both subgroups. After a month of treatment,
      erythrocyte GSH-Px activity in subgroups A and C was not significantly different
      from that observed in EW. After a month of treatment, no significant variation
      was found in subgroup B nor in the control group. These results strongly suggest
      that when plasma E2 is restored to physiological levels in AP, it stimulates
      erythrocyte GSH-Px activity. Progesterone therapy did not induce significant
      modifications.

PMID- 8989255
TI  - A combined test using desmopressin and corticotropin-releasing hormone in the
      differential diagnosis of Cushing's syndrome.
AB  - To assess the ability of desmopressin to differentiate between pituitary and
      ectopic ACTH-dependent Cushing's syndrome and to determine whether diagnostic
      accuracy could be improved by administering it together with human sequence CRH,
      we examined its effects on cortisol and ACTH secretion when given alone or in
      combination with CRH in patients with Cushing's syndrome of varied etiology and
      compared these data to the results of a standard CRH test in the same
      individuals. Each patient was studied on three occasions, in random order,
      separated by at least 48 h. At 0900 h, via an indwelling forearm cannula, 10
      micrograms desmopressin, 100 micrograms CRH, or a combination of the two were
      given as an iv bolus; thereafter, blood was drawn every 15 min for 2 h. The
      responses to the individual agents were determined according to the timing and
      calculation criteria suggested by Nieman et al. (1993). A total of 25 patients
      with Cushing's syndrome were studied: 17 patients with pituitary-dependent
      Cushing's syndrome, Cushing's disease (CD); 5 patients with occult ectopic ACTH
      secretion (EC); and 3 patients with primary adrenal (ACTH-independent) Cushing's
      syndrome. In this series, the best discrimination among ACTH-dependent patient
      groups was achieved using the combined test. Using the responses of plasma
      cortisol, all 17 patients with CD showed a rise greater than any of the 5
      patients with EC, whereas 1 patient with CD showed a plasma ACTH response within
      the range seen in the patients with EC. Plasma cortisol responses to desmopressin
      alone were seen in 14 of 17 patients with CD and 1 of 5 patients with EC and,
      after CRH alone, in 15 of 17 patients with CD but in no patient with EC. In
      contrast, plasma ACTH responses after CRH alone were seen in 14 of 17 patients
      with CD and 2 of 5 patients with EC and, after desmopressin alone, in 12 of 17
      with CD and 3 of 5 with EC, thus indicating overlapping responses between the
      groups and poorer discrimination. No responses were seen in the ACTH-independent
      group. These data indicate that desmopressin causes the secretion of ACTH and
      cortisol in patients with ACTH-dependent Cushing's syndrome, and that in
      combination with CRH, it may provide an improvement over the standard CRH test in
      the differential diagnosis of ACTH-dependent Cushing's syndrome. Furthermore,
      these data suggest that there may be abnormalities in vasopressin receptor
      function or number in ACTH-secreting tumors.

PMID- 8989256
TI  - Transfer of dehydroepiandrosterone- and pregnenolone-fatty acid esters between
      human lipoproteins.
AB  - Dehydroepiandrosterone (DHEA)- and pregnenolone (PREG)-fatty acid esters (FA) are
      formed in plasma high density lipoproteins (HDL), whereas they accumulate in very
      low density lipoproteins (VLDL), low density lipoproteins (LDL), and HDL. We have
      hypothesized that these lipoidal steroids could be transferred from HDL to VLDL
      and LDL by the cholesteryl ester (CE) transfer protein (CETP), which mediates CE
      transfer activity in human plasma. In this study, we further investigated this
      hypothesis. Lipoproteins and lipoprotein-deficient plasma (LPDP) were purified
      and analyzed by Western blots. LPDP was rich in CETP, in contrast to lipoprotein
      preparations, which contained very low amounts. Using these preparations in in
      vitro transfer assays, CE transfer from radiolabeled steroid ester-HDL to VLDL or
      LDL was only observed in the presence of LPDP. In contrast, time- and temperature
      dependent transfer of DHEA-FA and PREG-FA were observed in the absence of LPDP.
      The addition of LPDP had no effect on the DHEA-FA transfer rate, whereas the PREG
      FA transfer rate was increased. Moreover, in the absence of LPDP, no decrease in
      the transfer levels of DHEA-FA and PREG-FA was observed after the removal of CETP
      from lipoprotein preparations by immunoaffinity column chromatography. The PREG
      FA transfer activity of LPDP was studied using the anti-CETP monoclonal antibody
      TP-2, which is known to block the CE transfer activity of CETP. In the presence
      of LPDP, this antibody led to a dose-dependent decrease in CE transfer activity,
      whereas PREG-FA transfer activity was unaffected. In conclusion, we have shown
      that DHEA-FA and PREG-FA are transferred from HDL to VLDL and LDL by a CETP
      independent mechanism. There is a major difference in the transport of lipoidal
      steroids by human lipoproteins compared to that of CE.

PMID- 8989257
TI  - Biological mechanisms underlying the clinical effects of RU 486: modulation of
      cultured endometrial stromal cell stromelysin-1 and prolactin expression.
AB  - During in vitro decidualization of human endometrial stromal cells (HESCs),
      medroxyprogesterone acetate (MPA) inhibits expression of the potent extracellular
      matrix (ECM)-degrading protease stromelysin-1 (MMP-3), but enhances PRL
      expression. Consistent with its priming role in vivo, estradiol (E2) augments
      these effects. In the current study, immunoblot analysis revealed that
      coincubation with 10(-6) M RU 486 blocked the inhibition in HESC-secreted MMP-3
      levels (50,000 mol wt) evoked by 10(-8) M E2 + 10(-7) M MPA. Although MPA can act
      as a glucocorticoid, the HESCs were refractory to 10(-7) M dexamethasone added
      alone or with E2. Because E2 elevates progesterone but not glucocorticoid
      receptor levels, MPA and RU 486 control MMP-3 expression as a progestin and
      antiprogestin, respectively. To study RU 486 involvement in steroid withdrawal
      leading to menstruation, HESCs were decidualized during 10 days incubation with
      E2 + MPA, and parallel cultures were kept in E2 + MPA or withdrawn to either
      control or RU 486-containing medium. Compared with E2 + MPA-suppressed HESCs,
      increases in levels of secreted MMP-3 (2.0-fold), and its 2.1-kilobase messenger
      RNA (10-fold) were observed in HESCs after 4 days of withdrawal to control
      medium, with much greater increases seen in RU 486-containing medium (10-fold
      protein, 100-fold messenger RNA). Previously, we showed that RU 486 up-regulated
      E2 + MPA-inhibited plasminogen activator expression in the cultured HESCs.
      Extrapolation of these in vitro observations to endometrial events following RU
      486 administration suggests that coordinate enhancement of MMP-3 and plasminogen
      activator expression promotes proteolysis of the stromal/decidual ECM, which
      leads to endometrial sloughing. Moreover, destabilization of endometrial
      microvessels resulting from degradation of their surrounding ECM is consistent
      with the heavy menstrual bleeding stemming from RU 486 administration. However,
      in contrast to the marked RU 486-initiated reversal of MMP-3 expression, RU 486
      did not significantly reverse E2 + MPA-enhanced PRL secretion by the cultured
      HESCs. Interestingly, decidual PRL, unlike decidual MMP-3, does not appear to
      play a role in menstruation. Interleukin-1 beta counteracted E2 + MPA-mediated
      inhibition of secreted MMP-3 levels, implying that leukocyte/trophoblast-derived
      cytokines can modulate steroid-regulated MMP-3 expression by stromal/decidual
      cells during menstruation and pregnancy.

PMID- 8989258
TI  - Synergistic effect of partially inactivating mutations in steroid 21-hydroxylase
      deficiency.
AB  - Lesions in the gene encoding steroid 21-hydroxylase result in congenital adrenal
      hyperplasia, with impaired secretion of cortisol and aldosterone from the adrenal
      cortex and overproduction of androgens. Mild forms of the disease cause late
      onset symptoms of hyperandrogenism and are thought to be largely underdiagnosed.
      A limited number of mutations account for the majority of mutated alleles, but
      additional rare mutations are responsible for the symptoms in some patients. We
      previously reported a rare allele in two siblings with late-onset disease. This
      allele contained three sequence alterations, a C to T transition 4 bases upstream
      of translation initiation, a CCG to CTG change at codon 105 (P105L), and a CCC to
      TCC transition at codon 453 (P453S). The latter mutation has been found in other
      ethnic groups, whereas P105L seems to be unique to this family. We have now
      analyzed the functional consequences of the -4, P105L, and P453S sequence
      alterations by in vitro translation and after expression of mutant enzyme in
      cultured cells. As expected, the base substitution at position-4 had no
      measurable effect on gene expression. The P105L mutation reduced enzyme activity
      to 62% for 17-hydroxyprogesterone and 64% for progesterone, and the P453S
      mutation reduced activity to 68% and 46%, respectively. When present in
      combination, the two mutations caused a reduction of enzyme activity to 10% for
      17-hydroxyprogesterone and 7% for progesterone. These results indicate that P105L
      and P453S can be expected to result in a very subtle disease manifestation when
      not found in combination, motivating their inclusion when genotyping to ascertain
      undiagnosed patients with the mildest forms of 21-hydroxylase deficiency.

PMID- 8989259
TI  - Aromatase activity and expression in breast cancer and benign breast tissue
      stromal cells.
AB  - In situ estrogen synthesis by hormone-dependent breast cancers could potentially
      regulate cellular proliferation through autocrine or paracrine mechanisms.
      Several biochemical studies have demonstrated activity of the enzyme aromatase,
      the rate-limiting step for estrogen synthesis, in breast tumor homogenates. Prior
      immunohistochemical studies in breast neoplasms demonstrated aromatase antibody
      binding to both stroma and parenchyma, but biochemically measured enzyme activity
      significantly correlated only with the level of staining in the stromal
      component. The present study sought to provide more direct evidence of the
      predominant role for stromal cell aromatase in breast tumor tissue. Accordingly,
      breast tumor stromal and epithelial cells were examined for aromatase enzyme
      activity and messenger ribonucleic acid (mRNA) expression. Stromal and epithelial
      cells from benign tissue served as a means of comparing activity and regulation
      in benign and tumor tissue. Enzyme activity in stromal cells from breast tumor
      tissue was low basally, but increased by 30- to 1200-fold when induced by
      dexamethasone. Combining dexamethasone with phorbol esters and cAMP produced an
      additional 1.2- to 4.1-fold stimulation. Analyses of exons III/V and exons IX/X
      demonstrated that aromatase mRNA expression was also substantially increased by
      these treatments. Increases in enzyme activity and mRNA expression in cells from
      benign breast stroma paralleled those observed in tumor stroma, although the
      increases in enzyme activity were generally lower. In contrast to the responses
      observed in stromal cells, epithelial cells from breast tumor or nonmalignant
      breast tissue were unresponsive to dexamethasone, either added alone or in
      combination with phorbol esters and cAMP. This study provides direct biochemical
      evidence that aromatase is present in stroma within breast tumors, as in
      surrounding tissues, and suggests that estrogen synthesis within the tumor may
      modulate tumor growth via a paracrine mechanism.

PMID- 8989260
TI  - Increased catabolism of 25-hydroxyvitamin D in patients with partial gastrectomy
      and elevated 1,25-dihydroxyvitamin D levels. Implications for metabolic bone
      disease.
AB  - Serum vitamin D metabolites and PTH were measured in seven subjects with a
      history of previous partial gastrectomy (PGX) and metabolic bone disease. The
      elimination t1/2 of [3H]25-hydroxyvitamin D3 ([3H]25OHD3) in serum was assessed
      after an iv pulse dose of 5 microCi [26,27-3H]25OHD3. Median serum 25OHD3 was
      37.5 (27.5-101.3) nmol/L, [normal range (NR) 10.8-58.5 nmol/L], mean serum 1,25
      dihydroxyvitamin D [1, 25-(OH)2D3] was raised at 175 +/- 72 pmol/L, (NR 48-120
      pmol/L) and mean PTH was also high, 67 +/- 27 ng/L, (NR 10-60 ng/L). Serum t1/2
      [3H]25OHD3 ranged from 10.9-21.2 days. A strong negative correlation existed
      between t1/2 [3H]25OHD3 and serum 1,25-(OH)2D3 [Spearman's rank correlation
      coefficient (r = -0.82, P = 0.002)] and PTH [Spearman's rank correlation
      coefficient (r = -0.81, P = 0.001)]. Four subjects who had high initial PTH
      concentrations (60-115 ng/L) and elevated 1,25-(OH)2D levels (162-300 pmol/L)
      were reassessed after calcium supplementation to suppress secondary
      hyperparathyroidism (2 degrees HPT). In this subgroup, after-treatment PTH fell
      from 82 +/- 24 to 52 +/- 24 ng/L (mean +/- SD), not significant; 1,25-(OH)2D fell
      from 210 +/- 61 to 116 +/- 28 pmol/L, P = 0.015; and t1/2 [3H]25OHD3 increased
      from 13.2 +/- 1.9 to 18.9 +/- 3.1 days, P = 0.012. Patients with PGX and evidence
      of 2 degrees HPT with elevated 1,25-(OH)2D have a reduced t1/2 [3H]25OHD3, and
      this may explain the increased susceptibility of the subjects to osteomalacia.
      Calcium supplementation suppresses 2 degrees HPT, increases t1/2 [3H]25OHD3 and
      may protect against PGX osteoporosis and osteomalacia.

PMID- 8989261
TI  - Genetic heterogeneity evidenced by low incidence of KAL-1 gene mutations in
      sporadic cases of gonadotropin-releasing hormone deficiency.
AB  - Isolated GnRH deficiency is a heritable condition characterized by a functional
      deficit in GnRH secretion. Familial cases with different modes of inheritance
      have been described, and the gene responsible for the X-linked form (KAL-1) has
      been identified. However, sporadic cases with no documented family history of
      GnRH deficiency account for the majority of the affected patients. For this
      reason, we sought to determine the frequency with which KAL-1 gene mutations
      occur in patients with sporadic GnRH deficiency. Only 1 of 21 patients with
      sporadic GnRH deficiency was found to bear a defect in the KAL-1 gene (a deletion
      of 14 bases starting at codon 464). Three types of polymorphic single base
      substitutions with no apparent correlation with GnRH deficiency were also
      detected in several patients. In each of 3 different patients with an X-linked
      mode of inheritance, 3 genetic defects, 2 point mutations and a small intragenic
      deletion, were detected. These defects consist of a single base mutation
      introducing a stop codon at position 328, a single base mutation resulting in a
      phenylalanine to leucine substitution at position 517, and a 9-base deletion at
      the 3'-exon-intron splice site of exon 8, respectively. All identified genetic
      defects occur within the fibronectin type III repeats of the predicted protein
      encoded by the KAL-1 gene. In conclusion, our study indicates that the incidence
      of genetic defects within the coding region of the KAL-1 gene in patients with
      sporadic GnRH deficiency is low (5-8%), thus supporting the idea that the X
      linked form of inheritance represents the least common form of the disease.

PMID- 8989262
TI  - Dimeric inhibins in amniotic fluid, maternal serum, and fetal serum in human
      pregnancy.
AB  - Using new specific and sensitive enzyme-linked immunosorbent assays for inhibin A
      and inhibin B, we measured these proteins in amniotic fluid (AF), maternal serum
      (MS), and umbilical cord serum in normal pregnancies. Inhibin A levels in AF rose
      from a median (10-90th percentile) level of 615 (158.2-1124.6) pg/mL at 14 weeks
      to 1336.0 (489.4-2084.1) pg/mL at 20 weeks, and inhibin B rose from 216.6 (67.4
      554.6) to 1078.2 (439.3-2482.2) pg/mL over the same period. In MS, inhibin A
      levels fell from a median (10-90th percentile) level of 177.5 (101.4-290.7) pg/mL
      at 10 weeks to a nadir of 111.9 (59.5-200.3) pg/mL at 17 weeks, rising again to
      180.3 (74.1-327.2) pg/mL at 20 weeks. No inhibin B was detectable in MS. In 47
      pairs of matched samples (14-16 weeks gestation) there was no correlation of
      inhibin A levels in AF with those in MS (r = 0.19; P > 0.05). In 45 term
      umbilical cord serum samples, no dimeric inhibin was detectable in serum from
      female babies, but inhibin B was detectable in male sera; the median (10-90th
      percentile) concentration was 167.4 (111.2-224.8) pg/mL. These data suggest that
      for the gestation periods studied, although the placenta secretes inhibin A,
      another source, probably the fetal membranes, secretes both inhibin A and inhibin
      B. Further, the presence of inhibin B in male fetuses is consistent with a
      testicular origin, suggesting that inhibin B may be important in the development
      of the fetal hypothalamo-pituitary-testicular axis.

PMID- 8989263
TI  - Serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and the
      acid-labile subunit as serum markers of body composition during growth hormone
      (GH) therapy in adults with GH deficiency.
AB  - Serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3
      (IGFBP-3), the acid-labile subunit (ALS), insulin, and IGFBP-1 were evaluated as
      indicators of body composition during GH replacement therapy in 20 GH-deficient
      patients (9 women and 11 men), aged 22-57 yr, with IGF-I levels below -2 SD. The
      mean GH dose was 0.128 +/- 0.003 IU/kg.week during the first month and thereafter
      0.23 +/- 0.01 IU/kg.week, divided into daily doses (0.7-4.3 IU/day). Serum levels
      of IGF-I, ALS, and IGFBP-3 above the normal range were reached in seven, five,
      and three subjects, respectively, after 12 months of GH therapy. IGF-I and ALS
      levels, but not IGFBP-3 levels, correlated with the total daily GH dose (r =
      0.676; P = 0.001 and r = 0.631; P = 0.003). The mean increase in lean body mass
      (LBM) measured by dual energy x-ray absorptiometry was 3.0 +/- 0.5 kg (P <
      0.001). At 12 months, the LBM values were significantly correlated to the IGF-I
      levels (r = 0.718; P < 0.001), but not to ALS or IGFBP-3 levels. No correlation
      was found before therapy, and the increase in LBM at 12 months correlated with
      the IGF-I increase (r = 0.514; P = 0.029) only after exclusion of two
      nonresponders. Both before and during therapy, LBM was inversely related to IGFBP
      1 (r = -0.715; P < 0.004 at 12 months). None of the GH-induced proteins could be
      used as indicators of body fat changes. In conclusion, both IGF-I and ALS can be
      used as indicators to avoid GH excess during replacement therapy, but only IGF-I
      relates to changes in LBM.

PMID- 8989264
TI  - Adult height in 24 patients treated for growth hormone deficiency and early
      puberty.
AB  - This study evaluates the capacity of treatment with the combination of growth
      hormone (GH) and gonadotropin releasing hormone (GnRH) analog to preserve the
      height potential of 24 patients (15 girls, 9 boys) with GH deficiency and early
      puberty (onset at 7.8 +/- 0.5 SE yr in girls and 9.0 +/- 0.7 yr in boys). All but
      4 were given cranial irradiation. They (group 1) were compared with 17 patients
      of normal pubertal age treated with GH for cranial irradiation-induced GH
      deficiency (group 2) and with 19 girls treated with GnRH analog for idiopathic
      central precocious puberty (group 3). The adult heights in groups 1, 2 and 3 were
      -0.5 +/- 0.2, -1.3 +/- 0.2, and -0.2 +/- 0.2 SD, significantly lower (P < 0.01)
      in group 2. They were lower than the target heights in groups 1 and 2 (P <
      0.001), and similar in group 3. They were similar to the predicted heights at the
      onset of therapy (combined, GH, or GnRH analog therapy), except in group 3 (adult
      height > predicted height, P < 0.0001) In group 1, as in group 3, the differences
      between adult and predicted heights (1.1 +/- 1.3 and 6.5 +/- 1.4 cm respectively)
      correlated positively with the difference between bone and chronological ages (P
      < 0.05), negatively with the predicted height (P < 0.002), and positively with
      the difference between the target and predicted heights (P < 0.001) at the onset
      of therapy. In conclusion, treatment with the combination of GH and GnRH analog
      in patients with GH deficiency and early puberty leads to a normal adult height.
      This height is similar to the predicted height at the onset of therapy but lower
      than the target height.

PMID- 8989265
TI  - Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in
      male depressed patients and healthy controls.
AB  - There is only sparse and ambiguous information about circadian and pulsatile
      secretion features of the hypothalamus-pituitary-adrenocortical system in
      depression. We studied 15 severely depressed (Hamilton Depression Scale 30.4 +/-
      6.7) male patients (age 22-72 yr; mean, 47.7 +/- 14.8) and 22 age-matched male
      controls (age 23-85 yr; mean, 53.1 +/- 18.2). Twenty-four-hour blood sampling
      from 0800-0800 h with 30-min sampling intervals was performed; from 1800-2400 h,
      blood was drawn every 10 min. Multivariate analysis of covariance, with the
      covariate being age, revealed mean 24-h cortisol (315.9 +/- 58.5 vs. 188.2 +/-
      27.3 nmol/L) and mean ACTH (7.82 +/- 1.94 vs. 5.79 +/- 1.28 pmol/L) to be
      significantly increased in depressed patients. The frequency of cortisol (2.6 +/-
      0.7 vs. 1.3 +/- 1.0 pulses/6 h) and ACTH (2.6 +/- 1.6 vs. 1.6 +/- 1.4 pulses/6 h)
      pulses during the evening were higher in patients compared to controls. The
      flattened circadian cortisol variation and reduced time of quiescence of cortisol
      secretory activity (140 +/- 116 vs. 305 +/- 184 min) in patients suggest
      disturbances of circadian functions. We conclude that increased hypothalamus
      pituitary-adrenocortical activity in depression is related to a greater frequency
      of episodic hormone release, and we hypothesize that the observed circadian
      changes might be partly due to altered mineralocorticoid and glucocorticoid
      receptor capacity and function.

PMID- 8989266
TI  - Inactivation of the tumor suppressor gene on 11q13 in brothers with familial
      acrogigantism without multiple endocrine neoplasia type 1.
AB  - Two of three brothers (the second and third brothers) and their uncle (their
      mother's brother) presented acrogigantism without multiple endocrine neoplasia
      type 1 (MEN 1). An invasive macroadenoma was found in the second brother, and it
      was histologically confirmed as a sparsely granulated GH cell adenoma. Two
      distinct microadenomas were found in the third brother, and these were
      histologically diagnosed as a mixed GH cell and PRL cell adenoma and a sparsely
      granulated GH cell adenoma, respectively. The loss of heterozygosity (LOH) was
      analyzed in two adenomas (GH cell adenoma from the second brother and a mixed GH
      cell and PRL cell adenoma from the third brother) by determining microsatellite
      polymorphisms of DNAs from tumors and patients' leukocytes. The LOH was found on
      the chromosome 11q13, whereas LOH was not detected on 1p31-36, 2p, 3p, 4, 5, 6p,
      7, 8, 9p21-22, 12p, and 19q13 in both pituitary adenomas examined. The haplotype
      analysis showed that the same haplotype on 11q13 was found in their mother and
      the unaffected first brother as well as in the affected uncle and two brothers.
      The deleted alleles on chromosome 11q13 in the tumors of two affected brothers
      were, however, restricted to those transmitted from their unaffected father.
      These data suggest that inactivation of the MEN 1 gene or other tumor suppressor
      genes on chromosome 11q13 plays an important role for the development of our
      familial acrogigantism without MEN 1.

PMID- 8989267
TI  - The effect of recombinant human growth hormone on glucose and leucine metabolism
      in Cushing's syndrome.
AB  - Cushing's syndrome is characterized by central obesity and muscle wasting. As GH
      is anabolic, it may be able to counteract the loss of body protein. To evaluate
      the potential therapeutic use of GH preoperatively, eight patients with Cushing's
      syndrome received sc injections of recombinant human GH (0.07 U/kg.day) for 7
      days. Whole body leucine and glucose turnover were measured after an infusion of
      [1-13C]leucine and [6,6-2H2]glucose before (day 0) and after 2 and 7 days of GH
      treatment. Compared with the value on day 0, there was a significant increase on
      days 2 and 7 in insulin (P < 0.005 and P < 0.001), C peptide (P < 0.01 and P <
      0.005), insulin-like growth factor I (P < 0.001), and glucose concentrations (P <
      0.01 and P < 0.005) and a decrease in the leucine concentration (P < 0.005).
      There was no significant change in glucose production rate, glucose MCR, leucine
      production rate (a measure of protein degradation), or nonoxidative leucine
      disappearance rate (a measure of protein synthesis). The leucine MCR was
      increased after 7 days (P < 0.05), and the clearance of leucine into protein
      (nonoxidative leucine disappearance rate/leucine concentration) was increased (P
      < 0.05) after 2 and 7 days of GH treatment. This is consistent with GH
      stimulating the availability of amino acid transporters. GH may, therefore, have
      a therapeutic role in the preoperative treatment of Cushing's syndrome.

PMID- 8989268
TI  - Olfactory dysfunction in type I pseudohypoparathyroidism: dissociation from Gs
      alpha protein deficiency.
AB  - The discovery of variably decreased olfactory ability in Type Ia
      pseudohypoparathyroidism (PHP), a syndrome in which generalized hormone
      resistance is associated with deficiency of the alpha chain of the stimulatory
      guanine nucleotide-binding protein (Gs alpha) of adenylyl cyclase, has been used
      to support the hypothesis that Gs alpha plays a major role in human olfactory
      transduction. However, only a limited number of olfactory tests have been
      administered to such patients, and these patients have other problems that might
      cause or contribute to their olfactory dysfunction, including an unusual
      constellation of skeletal and developmental deficits termed Albright hereditary
      osteodystrophy (AHO). In this study, we administered tests of odor detection,
      identification, and memory to (i) 13 patients with Type Ia PHP; (ii) 8 patients
      with Type Ib PHP; (iii) 7 patients with pseudopseudohypoparathyroidism (PPHP);
      and (iv) 3 sets of normal controls matched to these groups on the basis of age,
      gender, and smoking history. Although we confirm that PHP Type Ia patients
      evidence olfactory dysfunction, we also demonstrate that (i) patients with Type
      Ib PHP, who have no AHO, no generalized hormone resistance, and normal Gs alpha
      activity, also evidence olfactory dysfunction relative to matched controls; and
      (ii) patients with PPHP, who have AHO, no generalized hormone resistance, and
      deficient Gs alpha protein activity, have relatively normal olfactory function.
      These observations do not support the hypothesis that the olfactory dysfunction
      associated with PHP is the result of generalized Gs alpha protein deficiency and
      imply that other mechanisms (e.g. ones associated with PTH or PTHrP resistance)
      are responsible for the olfactory deficits of this disorder.

PMID- 8989269
TI  - Effect of tibolone on glucose and lipid metabolism in postmenopausal women.
AB  - The effect of tibolone, a new therapeutic agent for menopause, on glucose and
      lipid metabolism was investigated in 11 healthy postmenopausal women. At baseline
      and after 3 months of tibolone administration (2.5 mg/day), glucose metabolism
      was evaluated in each subject using both an oral glucose tolerance test (75 g)
      and the minimal model method of a frequently sampled intravenous glucose
      tolerance test. Frequently sampled intravenous glucose tolerance test allows the
      calculation of insulin sensitivity and peripheral glucose use independent of
      insulin. High-density lipoprotein-cholesterol, total cholesterol, apoprotein-A,
      and apoprotein-B measured in fasting conditions were not modified by tibolone,
      whereas triglycerides were reduced significantly (P < 0.01). Fasting levels of
      glucose were reduced significantly (P < 0.025), whereas those of insulin, C
      peptide, and the C-peptide/insulin ratio were not modified. Glucose, insulin, C
      peptide, and the C-peptide/insulin ratio responses to oral or iv glucose were not
      modified. Insulin sensitivity was inversely correlated to body mass index, and
      independent on that body mass index was significantly enhanced (P < 0.01).
      Glucose utilization independent of insulin was not modified. The present data
      indicate that tibolone does not negatively influence glucose metabolism and may
      indeed improve both the peripheral tissue sensitivity to insulin and the lipid
      profile.

PMID- 8989270
TI  - Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women.
AB  - Previously we demonstrated that low grade chronic metabolic acidosis exists
      normally in humans eating ordinary diets that yield normal net rates of
      endogenous acid production (EAP), and that the degree of acidosis increases with
      age. We hypothesize that such diet-dependent and age-amplifying low grade
      metabolic acidosis contributes to the decline in skeletal muscle mass that occurs
      normally with aging. This hypothesis is based on the reported finding that
      chronic metabolic acidosis induces muscle protein breakdown, and that correction
      of acidosis reverses the effect. Accordingly, in 14 healthy postmenopausal women
      residing in a General Clinical Research Center and eating a constant diet
      yielding a normal EAP rate, we tested whether correcting their "physiological"
      acidosis with orally administered potassium bicarbonate (KHCO3; 60-120 mmol/day
      for 18 days) reduces their urinary nitrogen loss. KHCO3 reduced EAP to nearly
      zero, significantly reduced the blood hydrogen ion concentration (P < 0.001), and
      increased the plasma bicarbonate concentration (P < 0.001), indicating that pre
      KHCO3, diet-dependent EAP was significantly perturbing systemic acid-base
      equilibrium, causing a low grade metabolic acidosis. Urinary ammonia nitrogen,
      urea nitrogen, and total nitrogen levels significantly decreased. The cumulative
      reduction in nitrogen excretion was 14.1 +/- 12.3 g (P < 0.001). Renal creatinine
      clearance and urine volume remained unchanged. We conclude that in postmenopausal
      women, neutralization of diet-induced EAP with KHCO3 corrects their preexisting
      diet-dependent low grade metabolic acidosis and significantly reduces their
      urinary nitrogen wasting. The magnitude of the KHCO3-induced nitrogen-sparing
      effect is potentially sufficient to both prevent continuing age-related loss of
      muscle mass and restore previously accrued deficits.

PMID- 8989271
TI  - The pathogenesis of age-related osteoporotic fracture: effects of dietary calcium
      deprivation.
AB  - The pathogenesis of osteoporotic fracture after the menopause is uncertain. We
      studied the effects of a 4-day low calcium diet on 17 subjects with vertebral
      osteoporotic fracture and 17 age-matched controls with a bone density within the
      young normal range and without fracture. At baseline, the osteoporotic patients
      were well matched to normal subjects in terms of calcium intake and absorption
      and renal function, but had higher bone turnover and relative secondary
      hyperparathyroidism. After the low calcium diet, the rise in calcitriol was
      deficient in the osteoporotic subjects. These data are consistent with the
      suggested pathogenesis of type II or age-related osteoporosis and show that in
      these subjects with osteoporotic fracture there was a primary defect in
      calcitriol production that resulted in secondary hyperparathyroidism. This defect
      may be the cause of the high bone turnover and may play an important role in the
      development of bone loss in these subjects.

PMID- 8989273
TI  - Acute effects of amiodarone administration on thyroid function in patients with
      cardiac arrhythmia.
AB  - Because little has been published on early effects of treatment with amiodarone
      on thyroid function, we studied serum total and free thyroid hormone, reverse T3,
      and TSH levels in patients with cardiac arrhythmias during the first 10 days of
      treatment with a loading dose of amiodarone by iv infusion. Twenty-four patients
      were enrolled in the study. A standardized loading regimen for the i.v. infusion
      of amiodarone was used. The protocol provided the i.v. infusion of 20 mg/kg per
      day on day 1, the i.v. infusion of 10 mg/kg per day on day 2, then 600 mg/day per
      os for 7-10 days, and finally, in patients chronically treated with the drug, the
      dose was gradually reduced to 400-200 mg/day per os. Total and free
      concentrations of T4 tended to progressively and significantly increase (P <
      0.0001 repeated measures ANOVA) starting from the fourth day of therapy, whereas
      total T3 decreased from the second day progressively (P < 0.0001) throughout the
      study; free T3 did not significantly change. TSH levels early and significantly
      (P < 0.001, by ANOVA) increased throughout the study, starting from the first day
      of therapy and reaching at 10 days a value 2.7 times higher than the basal value.
      Reverse T3 levels progressively and significantly (after 2 days of treatment)
      increased and paralleled the TSH values, reaching at the 10th day a value about 2
      times higher than basal value. In conclusion, our data suggest that after i.v.
      treatment with amiodarone: 1) TSH is the first hormone to change significantly
      followed by reverse T3, T4, and T3; 2) the progressive fall of T3 levels reflects
      an inhibition of the peripheral conversion of T4 to T3; 3) the observed later
      increase of total and free T4 levels may be explained by a contribution of direct
      thyroidal stimulation by TSH and/or by a reduction in T4 clearance.

PMID- 8989272
TI  - Dose-response relationships for alendronate treatment in osteoporotic elderly
      women. Alendronate Elderly Osteoporosis Study Centers.
AB  - Alendronate (ALN) is an aminobisphosphonate employed as an antiresorptive agent
      in the treatment of osteoporosis. The present study was carried out to determine
      dose-response relationships, particularly the effects of relatively low doses of
      ALN, on bone mineral density (BMD), biochemical indexes of bone and mineral
      metabolism, and bone histology, with particular attention to effects in elderly
      women. This prospective, randomized, double blind, 2-yr multicenter study
      compared the effects of placebo with those of 1.0, 2.5, or 5.0 mg ALN daily. All
      subjects received supplemental calcium (500 mg daily) as the carbonate. We
      studied 359 women with lumbar spine BMD at least 2.0 SD below the peak young
      adult mean. Subjects were stratified by age, with 135 aged 60-69 yr and 224 aged
      70-85 yr. Histomorphometry was performed on transiliac bone biopsies obtained
      from 104 subjects after 1 yr and from 83 subjects after 2 yr. This study
      elucidated the previously uninvestigated lower region of the dose-response curve
      for ALN in osteoporosis. Over 2 yr, treatment with 1.0, 2.5, or 5.0 mg/day
      increased lumbar spine BMD, on the average, by 0.65%, 3.54%, and 5.67%,
      respectively, compared with that in the placebo group (P < 0.001 vs. placebo for
      the 2.5 and 5 mg groups). Significant dose-related increases were also seen in
      BMD at appendicular sites and in total body BMD. Dose-dependent reductions in
      bone turnover to new steady states were indicated by serum and urine biochemical
      markers as well as by histomorphometry. There was also a dose-related reduction
      in the proportion of subjects suffering nonvertebral fractures (P < 0.05). Safety
      profiles were similar for the ALN and placebo groups and for both age strata.
      Efficacy was similar for both age strata. There was no evidence of impaired
      mineralization or other histological abnormalities due to ALN treatment. We
      conclude that treatment with ALN over a period of 2 yr was well tolerated and
      produced dose-dependent increases in BMD without evidence of a plateau over the
      dose range of 1.0-5.0 mg daily. One milligram daily did not result in a
      significant effect on BMD, and 5.0 mg daily produced favorable effects at all
      sites measured. Other studies have demonstrated somewhat greater effects on 10 mg
      daily. ALN, was equally effective and well tolerated in osteoporotic women over
      70 yr old as in younger women with the same condition.

PMID- 8989274
TI  - The parathyroid hormone circadian rhythm is truly endogenous--a general clinical
      research center study.
AB  - While circulating levels of PTH follow a diurnal pattern, it has been unclear
      whether these changes are truly endogenous or are dictated by external factors
      that themselves follow a diurnal pattern, such as sleep-wake cycles, light-dark
      cycles, meals, or posture. We evaluated the diurnal rhythm of PTH in 11 normal
      healthy male volunteers in our Intensive Physiologic Monitoring Unit. The first
      36 h spent under baseline conditions were followed by 28-40 h of constant routine
      conditions (CR; enforced wakefulness in the strict semirecumbent position, with
      the consumption of hourly snacks). During baseline conditions, PTH levels
      followed a bimodal diurnal rhythm with an average amplitude of 4.2 pg/mL. A
      primary peak (t1max) occurred at 0314 h, and the secondary peak (t2max) occurred
      at 1726 h, whereas the primary and secondary nadirs (t1min and t2min) took place,
      on the average, at 1041 and 2103 h, respectively. This rhythm was preserved under
      CR conditions, albeit with different characteristics, thus confirming its
      endogenous nature. The serum ionized calcium (Cai) demonstrated a rhythm in 3 of
      the 5 subjects studied that varied widely between individuals and did not have
      any apparent relation to PTH. Urinary calcium/creatinine (UCa/Cr), phosphate/Cr
      (UPO4/Cr), and sodium/Cr (UNa/Cr) ratios all followed a diurnal rhythm during the
      baseline day. These rhythms persisted during the CR, although with different
      characteristics for the first two parameters, whereas that of UNa/Cr was
      unchanged. In general, the temporal pattern for the UCa/Cr curve was a mirror
      image of the PTH curve, whereas the UPO4/Cr pattern moved in parallel with the
      PTH curve. In conclusion, PTH levels exhibit a diurnal rhythm that persists
      during a CR, thereby confirming that a large component of this rhythm is an
      endogenous circadian rhythm. The clinical relevance of this rhythm is reflected
      in the associated rhythms of biological markers of PTH effect at the kidney,
      namely UCa/Cr and UPO4/Cr.

PMID- 8989275
TI  - The maternal insulin-like growth factor (IGF) and IGF-binding protein response to
      trisomic pregnancy during the first trimester: a possible diagnostic tool for
      trisomy 18 pregnancies.
AB  - Many lines of evidence point to an important role for the insulin-like growth
      factors (IGFs) in embryonic and fetal growth in human pregnancy. The
      bioavailability of IGFs is modulated by IGF-binding proteins (IGFBP-1 to -6),
      whose permissive or inhibitory actions are regulated in part by posttranslational
      modification. In second and third trimester pregnancies, maternal IGFBP-1 is
      elevated in preeclampsia and intrauterine growth retardation. In the first
      trimester, trisomic pregnancies result in derangement of maternal serum levels of
      peptides, including hCG beta and pregnancy-associated plasma protein A. Trisomy
      18 is characterized by growth failure in the first trimester, whereas trisomy 21
      is not; thus, if maternal serum levels of IGFs and IGFBPs reflect fetal growth,
      changes specific to trisomy 18 may be expected. We report maternal serum levels
      of IGF-I, IGF-II, and IGFBP-1,-2, and -3; IGFBP-1 phosphorylation; and IGFBP-3
      proteolysis in pregnancies (n = 139) complicated by trisomy 18 or trisomy 21
      compared with those in normal controls. Maternal IGF-I, IGF-II, and IGFBP-3
      showed no significant difference between fetuses with a normal karyotype and
      those with trisomy 18 or 21. The mean IGFBP-1 level was significantly higher and
      the mean IGFBP-2 level was lower in fetuses with trisomy 18 compared with normal
      fetuses [108.8 +/- 6.1 vs. 36.7 +/- 1.9 micrograms/L (P = 0.0001) and 81.2 +/-
      5.5 vs. 206.1 +/- 10.2 micrograms/L (P = 0.0001), respectively]. There was no
      significant difference between the trisomy 21 and normal groups. The reduction in
      IGFBP-2 was confirmed by Western ligand and immunoblotting, and there was no
      evidence of variation in lower mol wt products to suggest differential
      proteolysis. IGFBP-1 phosphoforms and IGFBP-3 proteolysis were not significantly
      different between groups. The finding of altered maternal serum levels of IGFBP-1
      and IGFBP-2 specific to pregnancies complicated by trisomy 18 suggests that these
      binding proteins may be important mediators of fetal growth in the first
      trimester, and the clear differences in the ratio of IGFBP-1 to -2 may serve as
      an additional diagnostic marker for trisomy 18 pregnancies.

PMID- 8989276
TI  - Increased expression of Bcl-2 protein in human uterine leiomyoma and its up
      regulation by progesterone.
AB  - Uterine leiomyoma is the most common benign smooth muscle cell tumor of the
      myometrium. Although Bcl-2 protein is known to be an apoptosis-inhibiting gene
      product and to prevent apoptotic cell death in a variety of cells, there are no
      published data regarding whether human leiomyomas express Bcl-2 protein. In the
      present study, we examined the expression of Bcl-2 protein in leiomyomas in
      comparison with that in the normal myometrium using an immunohistochemical method
      and immunoblot analysis with a monoclonal antibody to human Bcl-2 protein.
      Furthermore, we investigated whether sex steroid hormones could influence the
      levels of Bcl-2 protein expression in leiomyoma cells cultured in vitro under
      serum-free, phenol red-free conditions. Immunohistochemical staining for Bcl-2
      protein was prominent in leiomyoma cells, but was scarcely present in normal
      myometrial smooth muscle cells. The expression of Bcl-2 protein in leiomyoma
      cells was most abundant in the secretory, progesterone-dominated, phase of the
      menstrual cycle, but was less abundant in the proliferative phase of the
      menstrual cycle. Western blot analyses of leiomyoma and myometrium tissue
      extracts revealed that Bcl-2 protein, with a molecular mass estimated at
      approximately 26 kDa, was abundantly present in leiomyoma tissue extracts, but
      was undetectable in normal myometrial tissue extracts. In monolayer cultures of
      uterine leiomyoma cells under a serum-free condition, the addition of
      progesterone (100 ng/mL) resulted in a striking increase in Bcl-2 protein
      expression in the cultured leiomyoma cells relative to that in control cultures,
      whereas the addition of 17 beta-estradiol (10 ng/mL) resulted in a reduction in
      Bcl-2 protein expression in the cells. The concentrations of sex steroids used
      were within the physiological tissue concentrations found in leiomyomas and
      myometrium. The present results suggest that the abundant expression of Bcl-2
      protein may have a molecular basis characteristic of leiomyomas in the human
      uterus and that progesterone may play a vital role in the enhanced expression of
      Bcl-2 protein in human uterine leiomyoma cells.

PMID- 8989277
TI  - Differential expression of 11 beta-hydroxysteroid dehydrogenase types 1 and 2 in
      human placenta and fetal membranes.
AB  - Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) are present in
      mammals. 11 beta HSD1 interconverts biologically active cortisol and inactive
      cortisone, whereas 11 beta HSD2 only converts cortisol to cortisone. Placental 11
      beta HSD has been proposed to protect the fetus from high level of maternal
      glucocorticoids. Although bidirectional activity of 11 beta HSD has been
      demonstrated in homogenized human placental tissues, the tissue and cellular
      distribution of 11 beta HSD1 has not been resolved. In this study, the cellular
      localization of 11 beta HSD1 protein and levels of its messenger ribonucleic acid
      (mRNA) in human placenta and fetal membranes were determined by
      immunohistochemistry and Northern blot analysis, respectively. We found that 11
      beta HSD1 immunoreactivity was present in the placental extravillous intermediate
      trophoblasts, chorion trophoblasts, amnion epithelial cells, and stromal cells of
      the decidua vera. Positive staining was also observed in the endothelium of the
      blood vessels in both placental villous tissue and umbilical cord. However, in
      contrast to previous reports of immunoreactive 11 beta HSD2 localization, 11 beta
      HSD1 immunoreactivity was undetectable in placental syncytiotrophoblast. Using a
      human 11 beta HSD1 complementary DNA as probe, a 1.5-kilobase mRNA transcript was
      detected in the chorion, amnion, and placental tissue, with the greatest amount
      in the chorion. In contrast, the 1.9-kilobase mRNA of 11 beta HSD2 was observed
      only in the placenta, not in the chorion and amnion. The process of labor had no
      significant effect on levels of 11 beta HSD1 or 11 beta HSD2 mRNA in the chorion
      or placenta. We conclude that there is a striking difference in the tissue
      localization of 11 beta HSD1 and 11 beta HSD2 expression in the late gestation
      human placenta and fetal membranes, which may discretely determine the
      accessibility of bioactive glucocorticoid to specific cell types.

PMID- 8989278
TI  - Two autonomous nodules of a patient with multinodular goiter harbor different
      activating mutations of the thyrotropin receptor gene.

PMID- 8989279
TI  - Gonadotropin-releasing hormone immunoreactivity in the nasal epithelia of adults
      with Kallmann's syndrome and isolated hypogonadotropic hypogonadism and in the
      early midtrimester human fetus.
AB  - GnRH-secreting neurons are known to originate in the epithelium of the medial
      olfactory placode, whence they migrate along the axons of the terminal nerve via
      the forebrain and into the hypothalamus. Synaptic contact between the developing
      olfactory bulbs and fascicles of the vomeronasal, terminal, and olfactory nerves
      does not occur in Kallmann's syndrome. Consequently, there is migration arrest of
      GnRH cells and partial or complete failure of formation of the olfactory bulbs,
      resulting in severe olfactory deficit and hypogonadotropic hypogonadism. In the
      present study, using an immunofluorescent, double immunostaining technique and
      confocal laser scanning microscopy, we observed GnRH-immunoreactive neurons in
      the hypothalamus of a 14-week-old human fetus. However, migration of GnRH neurons
      was not complete, and indeed, such cells were seen to be migrating along terminal
      nerve fascicles beneath the cribriform plate in a 16-week-old fetus. The same
      immunofluorescent technique demonstrated the presence of GnRH cells in biopsies
      of nasal mucosa obtained from three adults with Kallmann's syndrome, one
      normosmic subject with hypogonadotropic hypogonadism, and a eugonadal male
      cadaver. These findings are consistent with two different interpretations: the
      nasal GnRH neurons may be vestigial, representing cells that failed to migrate
      during embryogenesis; alternatively, they may have been generated de novo later
      in life, a possibility consistent with the recognized plasticity of human
      postnatal olfactory neuroepithelium. They also reveal that subjects with the
      normosmic (i.e. non-Kallmann's) form of GnRH deficiency are able to synthesize
      immunologically recognizable GnRH, implying that failure of GnRH synthesis is not
      responsible for this type of hypogonadotropic hypogonadism.

PMID- 8989280
TI  - Racial differences in plasma leptin concentrations in obese postmenopausal women.
AB  - Leptin may play an important role in the regulation of body weight by influencing
      energy intake and expenditure. Differences in body composition, resting energy
      expenditure (REE), and physical activity between African-American and Caucasian
      women could be reflective of racial differences in plasma leptin concentrations.
      Thus, we examined racial differences in leptin levels and the relationships of
      leptin to body composition and resting metabolism in obese postmenopausal African
      American (n = 28) and Caucasian (n = 29) women matched for level of body fat.
      African-American and Caucasian women were similar in age (64.1 +/- 1.3 vs. 63.2
      +/- 1.0 yr), body weight (84.7 +/- 3.3 vs. 80.4 +/- 1.3 kg), adipose tissue mass
      (39.7 +/- 2.8 vs. 38.0 +/- 1.0 kg), waist to hip ratio (0.81 +/- 0.02 vs. 0.81 +/
      0.01), and maximal aerobic capacity (1.5 +/- 0.05 vs. 1.6 +/- 0.05 L/min).
      African-American women had greater lean tissue mass than Caucasian women (41.8 +/
      1.1 vs. 39.3 +/- 0.6 kg; P = 0.05). The leptin concentration was 20% lower in
      African-American than Caucasian women (36.0 +/- 4.8 vs. 45.8 +/- 3.5; P < 0.05),
      whereas REE values were similar. Leptin correlated strongly with percent body fat
      in African-American (r = 0.71; P < 0.0001) and Caucasian women (r = 0.61; P <
      0.001) and with REE in African-American (r = 0.58; P < 0.001), but not Caucasian,
      women (r = 0.08). These findings suggest racial differences in plasma leptin
      levels and in leptin's role in the regulation of REE, which may play a role in
      the greater incidence of obesity in the African-American compared to the
      Caucasian population.

PMID- 8989281
TI  - Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea.
AB  - The possibility that chronic nutritional deficiency alters leptin regulation and
      its link to reproductive function was investigated by determining serum leptin
      levels during a 24-h period with controlled nutrient intake in highly trained
      athletes with and without menstrual cyclicity and in BMI-matched cycling
      sedentary controls (n = 8 per group). Our data show that 24th leptin levels were
      reduced equally (3-fold, P < 0.001) in both cyclic and amenorrheic athletes as
      compared to controls. Low leptin levels in the athletic groups were consistent
      with their reduction in body fat (r = 0.91, P < 0.0001) relative to BMI, but were
      also influenced by the presence of low insulin (r = 0.70, P < 0.001) and elevated
      cortisol (r = -0.65, P < 0.001) levels. A diurnal pattern of 24h leptin levels,
      with an approximate 50% rise (P < 0.001) from nadir (0900h) to peak (0100h), was
      present in normally cycling athletes and controls and was strikingly absent in
      amenorrheic athletes. The absolute increase in leptin levels from nadir to peak
      was directly related to insulin excursions in response to meals (r = 0.60, P =
      .002) and inversely related to the amplitude of the 24h cortisol rhythm (r = 
      0.70, P = .0002). These findings are consistent with a link between the
      functionality of adipocytes, nutritional status, and integrity of the
      reproductive axis in humans.

PMID- 8989282
TI  - Low dose ACTH test--a word of caution to the word of caution: when and how to use
      it.

PMID- 8989283
TI  - Activity of the renin-angiotensin-aldosterone axis is dependent on the occurrence
      of edema in growth hormone (GH)-deficient adults treated with GH.

PMID- 8989284
TI  - Geriatric dentistry at the crossroads.

PMID- 8989285
TI  - What does patient-centered care mean in an academic health center? An
      introduction.

PMID- 8989286
TI  - Health care relationships: instruments for effective patient-focused care in the
      academic health center.

PMID- 8989287
TI  - Patient-centered care in an academic health center: an administrator's
      perspective.

PMID- 8989288
TI  - Patient-centered care in an academic health center: faculty perspective.

PMID- 8989290
TI  - What does patient-centered care mean in an academic health center? A conclusion.

PMID- 8989289
TI  - The provider-patient relationship in academic health centers: the movement toward
      patient-centered care.

PMID- 8989291
TI  - A survey of predoctoral dental basic pharmacology education.
AB  - A survey of fifty-one of the fifty-three dental schools in the continental United
      States provided information about pharmacology curriculum content and time
      allocation. Most dental schools offer a traditional didactic course in basic
      pharmacology, with about 50 percent of the medical school-based (MSB) and 75
      percent of the dental school-based (DSB) programs providing additional
      pharmacology material in other basic and clinical courses. The four combined
      medical-dental (M-D) student courses have more hours of instruction, clinical
      conferences and reviews, and number of instructors than either the dental school-
      or medical school-based courses. DSB and MSB pharmacology courses were similar in
      most regards, with a relatively low compliance with the current curriculum
      guidelines. The DSB and MSB courses provided more time for neuropharmacology and
      less time for agents related to various organ systems than the M-D courses. There
      is considerable potential to improve pharmacology instruction by expanding the
      inclusion of pharmacology in other courses, increasing the number of clinical
      conferences and discussions, and offering problem-based-learning sessions.

PMID- 8989292
TI  - An audit system for assessing dental record keeping.

PMID- 8989293
TI  - Resection of the caudate lobe of the liver for primary and recurrent
      hepatocellular carcinomas.
AB  - BACKGROUND: Resection of the caudate lobe of the liver to treat malignancies has
      recently received attention, but long-term results after such resection for
      hepatocellular carcinoma have not been reported for an acceptable number of
      patients. This study analyzed the short- and long-term results after resection of
      the caudate lobe for primary and recurrent hepatocellular carcinoma in 19
      patients. STUDY DESIGN: Complete or partial resection of the caudate lobe was
      performed for the treatment of primary (n = 13) and recurrent (n = 6)
      hepatocellular carcinoma. Eleven patients had a solitary tumor only in the
      caudate lobe, but eight patients had tumors in other segments of the liver as
      well. There were 16 men and 3 women. Age ranged from 35 to 79 years, averaging 63
      years. Clinicopathologic features of these cases were evaluated from various
      viewpoints. RESULTS: The duration of the operation ranged from 80 to 250 minutes
      (mean plus or minus standard deviation; 149 +/- 47) and blood loss from 200 to
      2,400 g (836 +/- 651). Four patients (21.8 percent) had postoperative
      complications and one (5.3 percent) died of postoperative variceal bleeding.
      Tumor size ranged from 1.0 to 6.0 cm, averaging 3.7 +/- 1.4. A capsule was seen
      around the tumor in 68.4 percent, daughter nodules in 5.3 percent, and vascular
      invasion in 31.2 percent. Hepatic cirrhosis was present in 15 patients and
      chronic hepatitis in four. The 5-year survival rate in all patients was 31.3
      percent. The survival rate was significantly better in patients with primary
      hepatocellular carcinoma than in those with recurrent tumors (49.2 percent
      compared with none) because of frequent recurrence in the latter group.
      CONCLUSIONS: Resection of the caudate lobe of the liver for hepatocellular
      carcinoma associated with chronic hepatic disease can be performed safely with a
      satisfactory long-term result, particularly in patients with primary tumors in
      this lobe.

PMID- 8989294
TI  - Factors predicting hospitalization after operative treatment for gastric
      carcinoma in patients older than 70 years.
AB  - BACKGROUND: Variable reports exist about the early and long-term outcome after
      operative treatment for gastric carcinoma in the elderly. This study was designed
      to describe perioperative morbidity and factors influencing the length of
      hospitalization in patients older than 70 years of age in a tertiary care cancer
      center. METHODS: Patient information for a 10-year period, between July 1985 and
      July 1995, was obtained through a prospective database and chart review.
      Complications and length of stay were tabulated. Patient-, disease-, and
      treatment-related factors and their influence on outcome were compared by
      univariate and multivariate analysis using nonparametric product-limit models.
      RESULTS: Of 385 patients aged 71 years or older with gastric adenocarcinoma, 310
      underwent resection. Postoperative complications occurred in 47.1 percent.
      Infectious complications predominated, most frequently involving intra-abdominal
      and pulmonary sites. Perioperative mortality was 7.1 percent. The median
      postoperative length of stay was 13 days (95 percent confidence interval 12 to 14
      days; 25th percentile, 10 days; 75th percentile, 20 days). Factors independently
      predicting an increased duration of stay were presence of any complications, the
      type of resection, site of the primary carcinoma, and presence of postoperative
      infection. Complications added 30.4 percent of total patient days, or an average
      of 11.5 hospital days per patient with a complication. Although patients with
      postoperative complications had inferior overall and disease-specific survival,
      this was not an independent prognostic variable. Compared with patients younger
      than 70 years of age, elderly patients had a significantly increased hospital
      stay. CONCLUSIONS: The single most important factor leading to increased length
      of hospitalization is the occurrence of any complication. Although complicated by
      higher morbidity and mortality, the resection of gastric carcinoma in elderly
      patients can be performed relatively safely and leads to survival that is
      comparable to younger patients. The findings support careful patient selection
      and optimal preparation of elderly patients undergoing resection for gastric
      carcinoma.

PMID- 8989295
TI  - Gastrectomy with combined resection of other organs for carcinoma of the stomach
      with invasion to adjacent organs: clinical efficacy in a retrospective study.
AB  - BACKGROUND: Carcinoma of the stomach invading one or more adjacent organs raises
      serious concerns over en bloc dissection because en bloc resection has an
      associated high risk and such advanced carcinoma is frequently associated with
      incurable factors. Thus, it is important to understand the efficacy of
      gastrectomy combined with other organ resection and to refine the indications for
      en bloc dissection. STUDY DESIGN: Seventy-seven patients with carcinoma of the
      stomach directly invading adjacent organs or structures were analyzed
      retrospectively to investigate the efficacy of en bloc resection. Forty-one
      patients underwent gastrectomy combined with resection of one or more invaded
      organs (combined resection group), while the other 36 patients underwent
      gastrectomy with palliative abrasion between the primary tumor and the invasion
      site (noncombined resection group). RESULTS: The five-year survival rate was 23
      percent in the combined resection group and 0 percent in the noncombined
      resection group (p < .05). The 23 curative cases and 18 noncurative cases in the
      combined resection group had a survival rate of 41 percent and 0 percent,
      respectively (p < .05). The survival rate after a single organ resection was 29
      percent, and after a multiple organ resection, 0 percent (p < .05). Cases of
      carcinoma invading either the pancreas or mesocolon had a slightly but not
      significantly better prognosis. In Borrmann type IV carcinoma there was no
      difference in survival between the curative and noncurative operation. Cases with
      P1 dissemination had a better prognosis than those of P2 and P3 dissemination.
      CONCLUSIONS: The best indication for an en bloc combined organ resection was an
      invasion limited to only one other organ, not more than N2, no incurable factor,
      and any type except Borrmann type IV. Additionally, an en bloc combined resection
      would be worth trying for any type of gastric carcinoma with not more than P1
      dissemination and with no other incurable factor.

PMID- 8989296
TI  - Cost-utility analysis of contaminated appendectomy wounds.
AB  - BACKGROUND: The influence of patient preference and treatment costs has not been
      considered in previous analyses of wound management decisions for contaminated
      right lower quadrant incisions. STUDY DESIGN: We performed a decision and cost
      utility analysis, conducting a MEDLINE search of the postappendectomy wound
      infection literature to establish assumptions and assign baseline probability
      estimates. Institution-specific cost data were obtained, and utility assignments
      were made by the authors. Studies used to assign baseline probabilities fulfilled
      the following criteria: perforated appendix or gangrenous appendicitis, use of
      perioperative antibiotics active against aerobic and anaerobic bacteria, and data
      stratified by wound management, operative findings, and infection rate. RESULTS:
      We constructed a decision tree comparing three methods of wound management for
      contaminated right lower quadrant incisions: primary closure, delayed primary
      closure, and secondary closure. Utility (a quality of life measure) was assigned
      to ultimate health states to incorporate patient preference. We calculated the
      cost-utility for each method of wound management and found that primary closure
      was of optimum cost-utility compared with delayed primary closure and secondary
      closure. To gain one quality-adjusted life year treating a population of patients
      with contaminated incisions, primary closure saves $22,635 over delayed primary
      closure and another $22,340 over secondary closure. This decision, tested by two
      way sensitivity analyses, was sensitive only to high primary closure infection
      rates. CONCLUSIONS: Challenging traditional surgical dogma, cost-utility analysis
      shows that primary closure is the favored method of management for contaminated
      right lower quadrant incisions. This analysis is specific to right lower quadrant
      incisions and the conclusion is valid for all estimated primary infection rates
      less than 0.27.

PMID- 8989298
TI  - Acute protein-calorie malnutrition impairs wound healing: a possible role of
      decreased wound nitric oxide synthesis.
AB  - BACKGROUND: Nitric oxide is synthesized in wounds. Systemic inhibition of wound
      nitric oxide synthesis decreases wound collagen accumulation and wound mechanical
      strength. The role of nitric oxide during impaired healing is not known. In a
      model of impaired wound healing induced by acute protein-calorie malnutrition, we
      correlated wound healing parameters with wound nitric oxide synthesis. STUDY
      DESIGN: One group of Sprague-Dawley rats was rendered acutely malnourished by
      restricting its food intake to 50 percent of the food intake of an ad libitum-fed
      control group. Wound collagen accumulation and types I and III collagen gene
      expression were measured 10 days postwounding in subcutaneously implanted
      polyvinyl alcohol sponges. Nitric oxide synthesis was determined in wound fluid
      and in supernatants of wound cell cultures. RESULTS: Animals with acute protein
      calorie malnutrition lost 10.4 +/- 0.8 percent, while controls gained 17.5 +/-
      1.2 percent of their original body weight. Protein-calorie malnutrition reduced
      sponge hydroxyproline contents (995 +/- 84 compared with 1,580 +/- 109
      micrograms/100 mg sponge, p < .001), indicating diminished wound collagen
      accumulation. Gene expression of type III, but not type I, collagen was decreased
      in wounds of protein-calorie malnutrition animals. Nitrite/nitrate and citrulline
      concentrations in wound fluid (p < .01) and in wound cell supernatants (p < .001)
      were also lower in protein-calorie malnutrition animals, indicating a net
      decrease in nitric oxide production. CONCLUSIONS: Impaired wound collagen
      accumulation caused by protein-calorie malnutrition may be a reflection of
      reduced nitric oxide synthesis within the wound.

PMID- 8989297
TI  - Hyperamylasemia in response to ritodrine or ephedrine administered to pregnant
      women.
AB  - BACKGROUND: Ritodrine and ephedrine can induce hyperamylasemia in pregnant women.
      The incidence of these beta-agonist-induced hyperamylasemias and their
      interaction on serum amylase activity are not known. STUDY DESIGN: Serum amylase
      activity was determined 12 to 24 hours after the administration of ritodrine
      alone (n = 140), ephedrine alone (n = 160), ephedrine and ritodrine
      simultaneously (n = 34), and ephedrine after prolonged (> or = 7 days) use of
      ritodrine (n = 101). RESULTS: A significantly higher incidence of hyperamylasemia
      (amylase > 215 IU/L) was seen in a group treated with ritodrine alone (60/140, 43
      percent), ephedrine alone (54/160, 34 percent), or ephedrine plus ritodrine
      (24/34, 71 percent) compared with untreated pregnant women (21/426, 4.9 percent).
      There was no difference in the incidence of hyperamylasemia among the untreated
      pregnant women and women who received ephedrine after long-term ritodrine (8/101,
      7.9 percent). Isozyme patterns, examined in 72 out of the 146 women with
      hyperamylasemia after such medications, indicated that salivary-type amylase
      exclusively was hypersecreted. CONCLUSIONS: Clinical doses of beta-agonists such
      as ephedrine or ritodrine induce hypersecretion of salivary-type amylase in
      approximately one-third of women who are pregnant. Desensitization to beta
      agonists may occur after prolonged use of ritodrine.

PMID- 8989299
TI  - Illness behavior influences the outcome of laparoscopic antireflux surgery.
AB  - BACKGROUND: While gastroesophageal reflux is amenable to medical and surgical
      treatment, the severity of pathophysiologic changes of the disease correlates
      poorly with the symptomatology. Similarly, the overall successful outcome of
      surgical therapy can be lessened by the poor outcome in a small number of
      patients despite the technical success of the operation. We conducted a study to
      determine the influence of illness behavior on the outcome and efficacy of
      laparoscopic Nissen fundoplication. STUDY DESIGN: From a larger group of patients
      undergoing a laparoscopic Nissen fundoplication, 77 patients (57 male, 20 female)
      completed an illness behavior questionnaire before and after surgery. This
      previously validated questionnaire assessed 10 scales of illness behavior. The
      results were compared with visual analog scales of outcome for overall
      satisfaction, heartburn, and solid food dysphagia, which were elicited
      independently from a standardized clinical follow-up questionnaire. RESULTS:
      Patients completed the questionnaire on average 2 months before and 25 months
      after surgery. High preoperative and postoperative scores for the "affective" and
      "hypochondriacal" scales were associated with poorer satisfaction with the
      surgical outcome. Although successful relief of reflux symptoms was unrelated to
      any preoperative illness behavior scale, postoperative scores for "disease
      conviction" and "disease affirmation" were predictors of further symptomatic
      heartburn in a small group of patients. Dysphagia did not correlate with illness
      behavior. When preoperative and postoperative scores were compared, no change in
      illness behavior was demonstrated, with the exception of lower scores for disease
      conviction and disease affirmation. CONCLUSIONS: These results suggest that while
      patient perception of disease is improved by laparoscopic fundoplication, patient
      satisfaction with the surgical outcome is in part determined by preoperative
      illness behavior.

PMID- 8989300
TI  - The role of platelet-derived growth factor in intraluminal stented graft healing.
AB  - BACKGROUND: Intraluminally placed polytetrafluoroethylene grafts are associated
      with enhanced graft endothelialization and diminished intimal hyperplasia when
      compared with interposition grafts. This study determined the role of platelet
      derived growth factor in intraluminal graft healing. STUDY DESIGN: Thirty dogs
      underwent infrarenal abdominal aorta polytetrafluoroethylene interposition
      (control, n = 15) or intraluminal stented (n = 15) grafting. Grafts were
      explanted at 1, 3, and 6 weeks. The percent of graft area endothelialization and
      intima to media height ratios were calculated. By using protein electrophoresis
      and the Western blot technique, platelet-derived growth factor, identified by
      immunolabeling with anti-platelet-derived growth factor antibody, was isolated
      from proximal, mid-, and distal graft regions and was quantified using
      densitometry. RESULTS: Graft area endothelialization was 0 +/- 3.3 percent, 2.3
      +/- 3.3 percent, and 19.0 +/- 3.3 percent for 1-, 3-, and 6-week controls; and
      4.7 +/- 3.7 percent, 30.5 +/- 3.3 percent, and 86.8 +/- 3.3 percent for 1-, 3-,
      and 6-week stented grafts. Endothelialization was greater in stented grafts at 3
      and 6 weeks (p < .01). Proximal anastomosis intima to media height ratios were
      1.61 +/- 0.15, 1.54 +/- 0.14, and 1.48 +/- 0.15 for 1-, 3-, and 6-week control
      grafts, and 0.42 +/- 0.18, 0.41 +/- 0.15, and 0.47 +/- 0.14 for 1-, 3-, and 6
      week stented grafts. Similar intima to media height ratio values were present at
      the distal anastomosis. Lower intima to media height ratios were observed in all
      stented grafts (p < .01). The platelet-derived growth factor content at 1-, 3-,
      and 6-weeks was lower in all stented grafts when compared with controls. The
      content of platelet-derived growth factor was greatest in 3-week controls, with a
      significant difference noted in the mid-graft region (p < .05). The content of
      platelet-derived growth factor remained stable in all stented graft regions over
      6 weeks. An inverse correlation between stented graft platelet-derived growth
      factor content and endothelialization (r = -0.43) and a positive correlation with
      proximal anastomotic intimal hyperplasia (r = 0.73) were identified. CONCLUSIONS:
      Lower platelet-derived growth factor content is associated with decreased intimal
      hyperplasia and improved healing in intra-arterial polytetrafluoroethylene
      grafts.

PMID- 8989301
TI  - Routine use of open technique in laparoscopic operations.
AB  - BACKGROUND: The "blind" insertion of the Veress needle for insufflation of the
      peritoneal cavity with subsequent closed placement of the first trocar during
      laparoscopic abdominal procedures can result in severe major vascular and
      visceral injuries. An open technique was proposed as an alternative method for
      insufflation in patients with abdominal scars to reduce the possibility of such
      complications. The aim of this article is to report the results of our experience
      with the routine use of open technique in laparoscopic surgery. STUDY DESIGN:
      Open technique was routinely used and prospectively evaluated in 330 patients who
      underwent laparoscopic procedures. RESULTS: Laparoscopic conversion was necessary
      in 25 out of 330 cases (7.6 percent): in 20 cases for unclear biliary anatomy
      during laparoscopic cholecystectomy, and in 5 cases for minor hemorrhage that
      could not be managed by laparoscopy. In the 305 procedures completed by
      laparoscopy, 11 patients (3.6 percent) had 13 postoperative complications. These
      complications were all of minor importance and were always unrelated to trocar
      insertion; in particular, no major vascular or visceral injuries were observed.
      CONCLUSIONS: Routine use of open technique for pneumoperitoneum represents the
      best prevention of most of the severe trocar-related complications that are
      potentially avoidable.

PMID- 8989302
TI  - Colonic perforations after renal transplantation.
AB  - BACKGROUND: Perforation of the colon is a rare but serious complication in renal
      transplantation; allograft recipients constitute a patient population uniquely at
      risk with end-stage renal failure, maintenance therapy with dialysis before
      transplantation, and then chronic immunosuppression thereafter. STUDY DESIGN: In
      1,401 consecutive transplants performed between 1951 and 1995 at the Brigham and
      Women's Hospital, 30 recipients (2.1 percent) experienced 34 episodes of colonic
      perforations, 13 of which (38 percent) were fatal. The medical records and clinic
      charts of each person were analyzed for variables between those who survived and
      those who died of the colon perforation. RESULTS: Significant differences in
      patient demography and clinical and laboratory findings including age, mean
      corticosteroid dose, and nutritional status were noted between the two groups.
      Early diagnosis and intervention improved the prognosis; 22 percent of those
      operated on within 24 hours died; 47 percent died after delayed intervention.
      Excision of the lesion with end-to-end anastomosis was effective in most right
      colon perforations, and removal of the lesion and formation of an end-colostomy
      and Hartmann pouch was preferred in rectosigmoid perforations. The incidence and
      outcome of posttransplant colonic perforations were associated with the intensity
      of immunosuppression, with 28 percent of perforations occurring within the first
      month after engraftment and 47 percent within the first 3 months; the mean daily
      dose of corticosteroids was three times higher in those who died compared with
      those who survived. The levels of serum albumin were significantly lower among
      nonsurvivors. CONCLUSIONS: Colon perforation is a catastrophic event in
      immunosuppressed renal transplant recipients. Prompt diagnosis and treatment are
      critical; because of the masking effects of corticosteroids on symptoms and
      signs, a high index of suspicion and urgent investigation are indicated. Prompt
      surgical intervention and attention to the nutritional status are essential for
      survival.

PMID- 8989303
TI  - Long-term results after surgical treatment of renal hyperparathyroidism when
      fewer than four glands are identified at operation.
AB  - BACKGROUND: When fewer than four parathyroid glands are discovered during
      cervical exploration in cases of renal hyperparathyroidism, some have suggested
      that the glands could be resected and that no parathyroid tissue should be
      grafted. The aim of the present study was to evaluate this approach. Indeed, no
      detailed follow-up of such patients has been reported so far. STUDY DESIGN:
      Between September 1979 and July 1995, 157 patients underwent a cervical
      exploration for renal hyperparathyroidism in our department. In 23 cases, fewer
      than four parathyroid glands were found. The present study reports the results of
      16 of these patients who did not undergo autotransplantation with parathyroid
      tissue after resection of all identified glands. RESULTS: At their last visit,
      four patients had normal blood levels of intact parathyroid hormone 14 to 71
      months (median 60 months) after parathyroidectomy. The parathyroid hormone was
      not detectable in 2 patients at 16 and 76 months after operation. It was elevated
      in the 10 remaining patients, but the disease required no treatment or could be
      controlled medically in 7 patients with a follow-up ranging from 12 to 100 months
      (median 33 months). Two patients needed reoperation, one at 14 and one at 45
      months after the first operation. An ectopic gland was found in both cases. The
      last patient refused further surgical treatment and died after 13 months.
      CONCLUSIONS: In most cases, autotransplantation of parathyroid tissue is not
      necessary when fewer than four glands are identified during parathyroidectomy.
      When grafting was omitted, 14 of 16 patients had normal or elevated blood levels
      of intact parathyroid hormone 10 to 100 months after parathyroidectomy (median 45
      months). However, in two patients, intact parathyroid hormone was persistently
      undetectable for 16 to 76 months. This suggests that parathyroid tissue should be
      cryopreserved for delayed autotransplantation when the surgeon chooses not to
      graft parathyroid tissue.

PMID- 8989304
TI  - Resection of the caudate lobe of the liver.

PMID- 8989305
TI  - Surgical management of carcinoma of the stomach in elderly patients.

PMID- 8989306
TI  - A new technique for assessing the resectability of hilar cholangiocarcinoma:
      lifting of the umbilical portion of the portal vein.

PMID- 8989307
TI  - Local recurrence after operative treatment of rectal carcinoma: a strategy for
      change.

PMID- 8989308
TI  - Recurrent carotid artery stenosis.

PMID- 8989309
TI  - Long-term results of operation for carcinoma of the stomach in T1/T2 stages:
      critical evaluation of the concept of early carcinoma of the stomach.

PMID- 8989310
TI  - Rite of initiation.

PMID- 8989311
TI  - New RNA recognition features revealed in ancient ribosomal proteins.

PMID- 8989312
TI  - ATP binding proteins with different folds share a common ATP-binding structural
      motif.

PMID- 8989313
TI  - Database of three-dimensional structures of HIV proteinases.

PMID- 8989314
TI  - Large modular proteins by NMR.

PMID- 8989315
TI  - From Levinthal to pathways to funnels.
AB  - While the classical view of protein folding kinetics relies on phenomenological
      models, and regards folding intermediates in a structural way, the new view
      emphasizes the ensemble nature of protein conformations. Although folding has
      sometimes been regarded as a linear sequence of events, the new view sees folding
      as parallel microscopic multi-pathway diffusion-like processes. While the
      classical view invoked pathways to solve the problem of searching for the needle
      in the haystack, the pathway idea was then seen as conflicting with Anfinsen's
      experiments showing that folding is pathway-independent (Levinthal's paradox). In
      contrast, the new view sees no inherent paradox because it eliminates the pathway
      idea: folding can funnel to a single stable state by multiple routes in
      conformational space. The general energy landscape picture provides a conceptual
      framework for understanding both two-state and multi-state folding kinetics.
      Better tests of these ideas will come when new experiments become available for
      measuring not just averages of structural observables, but also correlations
      among their fluctuations. At that point we hope to learn much more about the real
      shapes of protein folding landscapes.

PMID- 8989316
TI  - Solution structure of the ribosomal RNA binding protein S15 from Thermus
      thermophilus.

PMID- 8989317
TI  - The RNA binding domain of ribosomal protein L11 is structurally similar to
      homeodomains.
AB  - The RNA binding domain of ribosomal protein L11 is strikingly similar to the
      homeodomain class of eukaryotic DNA binding proteins: it contains three alpha
      helices that superimpose with homeodomain alpha-helices, and some conserved
      residues required for rRNA recognition align with homeodomain helix III residues
      contacting DNA bases.

PMID- 8989318
TI  - Escherichia coli positive regulator OmpR has a large loop structure at the
      putative RNA polymerase interaction site.
AB  - The C-terminal DNA-binding domain of OmpR, a positive regulator involved in
      osmoregulation expression of the ompF and ompC genes in Escherichia coli, has a
      helix-turn-helix variant motif. The 'turn' region, consisting of 11 residues,
      forms an RNA polymerase contact site.

PMID- 8989319
TI  - The amino acid substitutions Ser288Gly and Val320Ala convert the cortisol
      producing enzyme, CYP11B1, into an aldosterone producing enzyme.
AB  - Transfection studies with cDNAs encoding hybrids between the highly similar
      cytochrome P450 enzymes, CYP11B1 (steroid 11 beta-hydroxylase) and CYP11B2
      (aldosterone synthase) have identified which amino acids determine the different
      activities of the enzymes.

PMID- 8989320
TI  - Product binding and role of the C-terminal region in class I D-fructose 1,6
      bisphosphate aldolase.
AB  - The structure of fructose 1,6-bisphosphate aldolase shows three distinct modes of
      product binding that are correlated to the disposition of the C-terminal region
      and depicts a possible trajectory for product exchange. The structure also
      indicates binding preference for monobasic triose phosphates.

PMID- 8989321
TI  - Projection structure of a gap junction membrane channel at 7 A resolution.
AB  - Electron cryo-microscopy and image analysis of frozen-hydrated, two-dimensional
      crystals of gap junction membrane channels formed by recombinant alpha 1 connexin
      (Cx43) reveal a ring of transmembrane alpha-helices that lines the aqueous pore
      and a second ring of alpha-helices in close contact with the membrane lipids.

PMID- 8989322
TI  - Picture story. DNA binding on a bender.

PMID- 8989323
TI  - Folding of cytochrome c initiated by submillisecond mixing.
AB  - Cytochrome c folding was initiated using a new solution mixer that provides a
      time window which covers over 90% of the burst phase unresolved by conventional
      stop-flow measurements. Folding was followed by resonance Raman scattering.
      Kinetic analysis of the high frequency Raman data indicates that a nascent phase
      occurs within the mixing dead time of 100 microseconds. A significant fraction of
      the protein was found to be trapped in a misfolded bis-histidine form during the
      nascent phase at pH 4.5, thereby preventing the protein from folding rapidly and
      homogeneously. The nascent phase was followed by a haem-ligand exchange phase
      that populates the native histidine-methionine coordinated form through a
      thermodynamically controlled equilibrium.

PMID- 8989324
TI  - Ligand exchange during cytochrome c folding.
AB  - Submillisecond folding of cytochrome c reveals that a nascent phase appears
      within the mixing dead time of 100 microseconds, followed by a ligand exchange
      reaction during which His 26/33, water and Met 80 are inter-exchanged as haem
      ligands through a thermodynamically controlled equilibrium. In the ligand
      exchange phase, the rate of formation of a misfolded histidine-histidine
      coordinated state (HH) decreases by two orders of magnitude as the pH is reduced
      from 5.9 to 4.5 due to the protonation of the misligated His 26/33. The
      activation energy barriers for the transitions from the histidine-water
      coordinated form (HW) to the histidine-methionine coordinated form and the HH
      form are 18 and 4 kcal mol-1 respectively, at pH 4.8. The activation energy
      barrier for protein to escape from the misligated HH to the HW form was measured
      to be 12 kcal mol-1, demonstrating the kinetic trapping effect of the misligated
      bis-histidine form. The development of the polypeptide tertiary structure near
      the haem is concomitant with the coordination of the native haem axial ligand.

PMID- 8989325
TI  - Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)
      huperzine A.
AB  - (-)-Huperzine A (HupA) is found in an extract from a club moss that has been used
      for centuries in Chinese folk medicine. Its action has been attributed to its
      ability to strongly inhibit acetylcholinesterase (AChE). The crystal structure of
      the complex of AChE with optically pure HupA at 2.5 A resolution shows an
      unexpected orientation for the inhibitor with surprisingly few strong direct
      interactions with protein residues to explain its high affinity. This structure
      is compared to the native structure of AChE devoid of any inhibitor as determined
      to the same resolution. An analysis of the affinities of structural analogues of
      HupA, correlated with their interactions with the protein, shows the importance
      of individual hydrophobic interactions between HupA and aromatic residues in the
      active-site gorge of AChE.

PMID- 8989326
TI  - The structure of MCP-1 in two crystal forms provides a rare example of variable
      quaternary interactions.
AB  - The X-ray crystal structure of recombinant human monocyte chemoattractant protein
      (MCP-1) has been solved in two crystal forms. One crystal form (P), refined to
      1.85 A resolution, contains a dimer in the asymmetric unit, while the other (I)
      contains a monomer and was refined at 2.4 A. Although both crystal forms grow
      together in the same droplet, the respective quaternary structures of the protein
      differ dramatically. In addition, both X-ray structures differ to a similar
      extent from the solution structure of MCP-1. Such extent of variability of
      quaternary structures is unprecedented. In the crystal structures, the well
      ordered N termini of MCP-1 form 3(10)-helices. Comparison of the three MCP-1
      structures revealed a direct correlation between the main-chain conformation of
      the first two cysteine residues and the quaternary arrangements. These data can
      be used to explain the structural basis for the assignment of residues
      responsible for biological activity.

PMID- 8989327
TI  - High resolution solution structure of ribosomal protein L11-C76, a helical
      protein with a flexible loop that becomes structured upon binding to RNA.
AB  - The structure of the C-terminal RNA recognition domain of ribosomal protein L11
      has been solved by heteronuclear three-dimensional nuclear magnetic resonance
      spectroscopy. Although the structure can be considered high resolution in the
      core, 15 residues between helix alpha 1 and strand beta 1 form an extended,
      unstructured loop. 15N transverse relaxation measurements suggest that the loop
      is moving on a picosecond-to-nanosecond time scale in the free protein but not in
      the protein bound to RNA. Chemical shifts differences between the free protein
      and the bound protein suggest that the loop as well as the C-terminal end of
      helix alpha 3 are involved in RNA binding.

PMID- 8989328
TI  - A test of the role of the proximal histidines in the Perutz model for
      cooperativity in haemoglobin.
AB  - Human haemoglobin has long been a paradigm for cooperative ligand binding and
      allostery. Through analysis of the crystal structures of deoxyhaemoglobin and
      liganded haemoglobin, Perutz proposed a model for cooperativity in which the bond
      between the proximal histidine and the protein couples haem rearrangements to
      protein structure rearrangements. Here we test this model by deleting the bonds
      between the histidine imidazole side chain and the polypeptide. This detachment
      method allows us to determine directly the contribution of proximal histidine
      coupling to cooperativity of distal ligand binding. Proximal detachment
      significantly increases ligand affinity, reduces cooperativity, and prevents
      quaternary structure switching, in accord with the Perutz model. Residual
      cooperativity indicates that additional haem communication pathways exist that do
      not involve the proximal histidine coupling mechanism.

PMID- 8989329
TI  - Are chest radiographs and electrocardiograms still valuable in evaluating new
      pediatric patients with heart murmurs or chest pain?
AB  - OBJECTIVES: To determine the usefulness of electrocardiography (ECG) and chest
      radiography (CXR) in evaluation of patients referred to the pediatric
      cardiologist for the evaluation of heart murmur or chest pain. DESIGN: In this
      prospective study, 106 consecutive outpatients were categorized with no heart
      disease, possible heart disease, or definite heart disease based on history and
      physical examination; they then underwent ECG and CXR. Studies were reviewed and
      the examining cardiologist could change the diagnosis and order an
      echocardiogram. SETTING: Academic pediatric cardiology practice. RESULTS: In
      patients thought to have no heart disease, the diagnosis was changed to definite
      heart disease in four solely on the basis of abnormal CXR or ECG. In 25 patients
      thought to have possible heart disease, the diagnosis was changed to no heart
      disease (7) or definite heart disease (5) after review of the CXR and ECG. All 25
      patients diagnosed with definite heart disease had this confirmed by abnormal CXR
      (2), ECG (3), both abnormal CXR and ECG, or echocardiogram (18). CONCLUSIONS: ECG
      and CXR helped diagnose heart disease in four patients thought to have no heart
      disease, helped to rule out lesions in seven patients with possible heart
      disease, helped diagnose heart disease in five patients thought to have possible
      heart disease, and helped confirm heart disease in nine patients. In these days
      of cost containment, routine ECG and CXR continue to be valuable tools for the
      pediatric cardiologist in evaluation of patients with heart murmurs or chest
      pain.

PMID- 8989330
TI  - Evidence from proton magnetic resonance spectroscopy for a metabolic cascade of
      neuronal damage in shaken baby syndrome.
AB  - OBJECTIVE: The purpose of this study was to use proton magnetic resonance
      spectroscopy (MRS) as a metabolic assay to describe biochemical changes during
      the evolution of neuronal injury in infants after shaken baby syndrome (SBS),
      that explain the disparity between apparent physical injury and the neurological
      deficit after SBS. METHODOLOGY: Three infants [6 months (A), 5 weeks (B), 7
      months (C)] with SBS were examined repeatedly using localized quantitative proton
      MRS. Examinations were performed on days 7 and 13 (A), on days 1, 3, 5, and 12
      (B), and on days 7 and 19 (C) posttrauma. Long-term follow-up examinations were
      performed 5 months posttrauma (A) and 4.6 months posttrauma (B). Data were
      compared to control data from 52 neurologically normal infants presented in a
      previous study. RESULTS: Spectra from parietal white matter obtained at
      approximately the same time after injury (5 to 7 days) showed markedly different
      patterns of abnormality. Infant A shows near normal levels of the neuronal marker
      N-acetyl aspartate, creatine, and phosphocreatine, although infant C shows absent
      N-acetyl aspartate, almost absent creatine and phosphocreatine, and a great
      excess of lactate/lipid and lipid. Analysis of the time course in infant B
      appears to connect these variations as markers of the severity of head injury
      suffered in the abuse, indicating a progression of biochemical abnormality. The
      principal cerebral metabolites detected by MRS that remain normal up to 24 hours
      fall precipitately to approximately 40% of normal within 5 to 12 days, with
      lactate/lipid and lipid levels more than doubling concentration between days 5
      and 12. CONCLUSIONS: A strong impression is gained of MRS as a prognostic marker
      because infant A recovered although infants B and C remained in a state
      consistent with compromised neurological capacity. Loss of integrity of the
      proton MR spectrum appears to signal irreversible neurological damage and occurs
      at a time when clinical and neurological status gives no indication of long-term
      outcome. These results suggest the value of sequential MRS in the management of
      SBS.

PMID- 8989331
TI  - Excess fruit juice consumption by preschool-aged children is associated with
      short stature and obesity.
AB  - BACKGROUND: In a referral population of young children, excessive fruit juice
      consumption has been reported to be a contributing factor in nonorganic failure
      to thrive. OBJECTIVE: To evaluate, in a population-based sample of healthy
      children, fruit juice consumption and its effects on growth parameters during
      early childhood. DESIGN: Cross-sectional study. SETTING: General primary care
      health center in upstate New York. PARTICIPANTS: One hundred sixteen 2-year-old
      children and one hundred seven 5-year-old children, who were scheduled for a
      nonacute visit, and their primary care taker/parent were recruited over a 2-year
      period. MEASUREMENTS: For 168 children (ninety-four 2-year-old children and
      seventy-four 5-year-old children), mean dietary intake was calculated from 7 days
      of written dietary records, entered, and analyzed using the Minnesota Nutrition
      Data System. Height was measured using a Harpenden Stadiometer. Weight was
      measured using a standard balance beam scale. RESULTS: The 2-year-old and 5-year
      old children consumed, on average, 5.9 and 5.0 fl oz/day of fruit juice and 9.8
      and 11.0 fl oz/day of milk, respectively. Nineteen children (11%) consumed > or =
      12 fl oz/day of juice. Forty-two percent of children consuming > or = 12 fl
      oz/day of juice had short stature (height less than 20th sex-specific percentile
      for age) vs 14% of children drinking less than 12 fl oz/day of juice. Obesity was
      more common among children drinking > or = 12 fl oz/day of juice compared with
      those drinking less juice: 53% vs 32% had a body mass index > or = 75th age- and
      sex-specific percentile; 32% vs 9% had a body mass index > or = 90th age- and sex
      specific percentile; and 32% vs 5% had a ponderal index > or = 90th age-specific
      percentile. After adjustment for maternal height, child age, child sex, and child
      age-sex interaction, children consuming > or = 12 fl oz/day of juice, compared
      with those drinking less than 12 fl oz/day of juice, were shorter (86.5 vs 89.3
      cm and 106.5 vs 111.2 cm for the 2-year-old and 5-year-old children,
      respectively) and more overweight (body mass index = 17.2 vs 16.3 kg/m2 and
      ponderal index = 18.4 vs 16.8 kg/m3). CONCLUSIONS: Consumption of > or = 12 fl
      oz/day of fruit juice by young children was associated with short stature and
      with obesity. Parents and care takers should limit young children's consumption
      of fruit juice to less than 12 fl oz/day.

PMID- 8989332
TI  - Comparison of ceftriaxone and trimethoprim-sulfamethoxazole for acute otitis
      media. Greater Boston Otitis Media Study Group.
AB  - OBJECTIVE: The purpose of this prospective, randomized, single-blind trial was to
      assess the clinical efficacy of a single intramuscular dose of ceftriaxone
      compared with 10 days of oral trimethoprim-sulfamethoxazole (TMP-SMZ) in treating
      acute otitis media (AOM). METHODS: Children aged 3 months through 3 years
      diagnosed with AOM (signs of acute illness plus evidence of middle-ear effusion)
      were randomized to treatment with either a single intramuscular dose of
      ceftriaxone (maximum dose of 50 mg/kg) or 10 days of oral trimethoprim
      sulfamethoxazole (8 mg of TMP and 40 mg of SMZ/kg/day in two divided doses).
      Children were evaluated at scheduled visits on days 3, 14, and 28, and the
      parents were telephoned on day 5. Children were assessed as cured, improved, or
      failed on day 3, and as cured or failed on days 14 and 28. Children ill at other
      times during the study period were, if possible, seen and assessed by the study
      team. RESULTS: Of 596 children enrolled during the study period, 484 were
      evaluable. Characteristics of evaluable subjects did not differ significantly by
      drug. On day 3, 223/241 children in the ceftriaxone group (92.5%) and 231/243
      (95.1%) in the TMP-SMZ group were cured or improved. On day 14, 158/197 (80.2%)
      in the ceftriaxone group and 174/212 (82.1%) in the TMP-SMZ group were cured. On
      day 28, 108/136 (79.4%) in the ceftriaxone group and 124/155 (80%) in the TMP-SMZ
      group were cured. Persistence of middle-ear fluid did not differ between groups
      at day 14 (55% in the ceftriaxone group vs 47% in the TMP-SMZ group; P = .16) or
      at day 28 (39% vs 43%; P = .48). Pain at the injection site persisting at day 3
      occurred in 8.4% of children receiving ceftriaxone. New diarrhea was more common
      in the ceftriaxone group (23.6% vs 9.2%; P < .001). CONCLUSION: A single
      intramuscular dose of ceftriaxone is comparable in clinical efficacy to 10 days
      of oral TMP-SMZ for treatment of AOM.

PMID- 8989333
TI  - Delayed puberty in girls with cystic fibrosis despite good clinical status.
AB  - BACKGROUND: Previous studies have shown that puberty is delayed among patients
      with cystic fibrosis (CF). Malnutrition has been considered the main etiologic
      factor. Today with improved medical therapy and nutritional support, most CF
      patients obtain an almost normal nutritional status. OBJECTIVES: To investigate
      whether pubertal development among female CF patients at the Stockholm CF Center
      was normal and, if not, what other parameters besides nutrition might influence
      this. METHODS: Seventeen patients were studied retrospectively regarding age at
      peak height velocity and menarche. Menarcheal age (MA) was compared with normal
      population data and related to clinical and nutritional status, genotype, oral
      glucose tolerance test (OGTT), and essential fatty acid levels. RESULTS: The mean
      age at peak height velocity (12.9 +/- 0.8 years) and at menarche (14.9 +/- 1.4
      years) was significantly higher in the CF patients compared with normal controls
      (11.9 +/- 1.0 years and 13.0 +/- 1.0 years, respectively). No correlation was
      found between menarchal age and nutritional or clinical parameters. The patients
      with pathological OGTT without overt diabetes were significantly older at
      menarche (15.8 +/- 1.7 years) compared with the patients with normal OGTT (14.3
      +/- 0.9 years). The patients who were homozygous for the most common mutation,
      deltaF508, were significantly older at menarche (15.2 +/- 1.9 years) than those
      who were not (14.7 +/- 0.9 years). CONCLUSIONS: Pubertal delay still existed
      among the CF patients despite good clinical status. The patients homozygous for
      deltaF508 and those with pathological OGTT showed the most delayed puberty.

PMID- 8989334
TI  - Varicella and zoster in children after kidney transplantation: long-term results
      of vaccination.
AB  - OBJECTIVE: To determine the long-term prevalence of varicella infection and
      herpes zoster after kidney transplantation and to assess the effectiveness of
      varicella immunization with the Oka attenuated strain. METHODS: This study
      involved 704 children and adolescents who received a kidney graft in our
      institution from 1973 to 1994 and had routinely been given varicella vaccine
      beginning in 1980 in preparation for transplantation. RESULTS: After vaccination
      62% of these patients still had varicella/zoster (VZ) antibodies at 1 year and
      42% after 10 years. After transplantation the incidence of varicella was
      significantly lower, 26/212 (12%), in patients who received immunization than in
      those who did not and had no history of varicella, 22/49 (45%). The disease was
      also significantly less severe in the vaccinated patients (three deaths among
      naive patients vs none among vacciness). In the vaccinees, varicella infection
      was observed only in those who did not develop or lost VZ antibodies; in
      addition, 21 patients of this subgroup had an asymptomatic seroconversion. Four
      of the 415 patients with a history of varicella had another episode of benign
      varicella after grafting. Herpes zoster was observed in 76 of the 704 patients
      included in the study. The prevalence differed according to VZ status at the time
      of grafting: 13% in patients with a history of varicella, 7% in the vacciness,
      and 38% in the naive patients at grafting who developed varicella. Three
      rejection episodes occurred in association with a varicella episode and four with
      a zoster episode, but graft function was only transiently impaired, and as a
      whole varicella or zoster did not significantly affect graft function or
      survival. CONCLUSION: Naive VZ patients with a kidney graft are at risk to
      develop severe varicella and this may be effectively prevented by available
      immunization.

PMID- 8989335
TI  - Beta 2-agonist metered dose inhaler overuse: psychological and demographic
      profiles.
AB  - OBJECTIVE: To identify psychological and demographic correlates of children and
      adolescents known to overuse beta 2-agonist metered dose inhalers (beta-MDIs).
      DESIGN: During residential care for severe asthma, demographic and psychological
      characteristics of 17 children and adolescents known to be beta-MDI overusers
      were compared with 38 asthmatic subjects of similar age without such history.
      RESULTS: beta-MDI overuse occurred among all groups; however, males, minorities,
      and those from lower socioeconomic groups were overrepresented. Overusers scored
      significantly lower on standardized IQ tests. Subtests of arithmetic for numeric
      reasoning, comprehension for understanding of social values, and picture
      completion for visual attention to detail were also significantly lower in beta
      MDI overusers, as were reading achievement tests. Testing also revealed
      tendencies toward dominant, shrewd, and undisciplined personality traits in the
      overusers. CONCLUSION: Recognition of these characteristics of children prone to
      beta-MDI overuse will raise the clinician's awareness of this potential. Greater
      efforts and alternative approaches toward education and treatment of the at-risk
      patient and family are indicated.

PMID- 8989336
TI  - Percutaneous transluminal angioplasty for renovascular hypertension in children:
      initial and long-term results.
AB  - OBJECTIVE: To evaluate the efficacy and safety of percutaneous transluminal renal
      angioplasty (PTRA) in children. METHODS: We performed aortography and attempted
      PTRA in 35 consecutive children (age 5 to 14 years, mean 10.8 +/- 2.5 years) with
      severe hypertension having > or = 75% renal artery stenosis (RAS). RESULTS: The
      stenosis was caused by aortoarteritis in 31 (88.6%) cases and by juvenile
      idiopathic fibromuscular disease (FMD) in four (11.4%) cases. Twenty-seven
      (77.1%) patients, including three having RAS of solitary functioning kidney with
      total occlusion of contralateral renal artery, had bilateral RAS and eight
      (22.9%) had unilateral RAS. PTRA was technically successful in 54 (91.5%) of 59
      stenotic lesions in 31 (88.6%) of 35 patients. Both aortoarteritis and FMD
      patients had significant decrease in RAS after PTRA. One patient had acute
      reocclusion of one renal artery after bilateral PTRA, which could be successfully
      opened by reangioplasty. Postangioplasty angiographic restudy performed in 18
      patients at 4 to 72 months (mean 23.1 +/- 27.9 months) after successful
      angioplasty showed restenosis in 8 (25.8%) of 31 lesions initially dilated and de
      novo lesions of aorta in two patients. All seven restenotic renal artery lesions
      attempted and both stenosis of aorta were successfully dilated. Twenty-nine of 31
      patients with successful PTRA have been followed up from 4 to 108 months (mean
      41.0 +/- 29.3 months). Mean systolic blood pressure decreased from 185.1 +/- 27.4
      to 120.6 +/- 19.2 mm Hg and mean diastolic blood pressure decreased from 118.4 +/
      13.2 to 84.6 +/- 10.4 mm Hg after PTRA. Twenty seven (93.1%) of these 29
      patients had benefical blood pressure response. Seventeen (58.6%) patients
      improved, 10 (34.5%) were cured, although 2 (6.9%) patients failed to respond to
      PTRA. Blood pressure response was better in FMD as compared to aortoarteritis
      group. Patients with unilateral RAS, discrete stenosis, and post-PTRA stenosis <
      or = 20% also identified good blood pressure response. CONCLUSION: Aortoarteritis
      is the most common cause of renovascular hypertension in South Asian children.
      PTRA is safe and highly effective and therefore should be the treatment of choice
      in pediatric renovascular hypertension.

PMID- 8989338
TI  - Toilet training and toileting refusal for stool only: a prospective study.
AB  - OBJECTIVE: To determine the incidence of toileting refusal for bowel movements
      and its outcome when toilet training children using a child-oriented approach.
      DESIGN: Prospective study. SETTING: Private suburban pediatric setting consisting
      of middle and upper middle class families. METHODS: Healthy children between 18
      and 30 months with no signs of developmental delay were enrolled in the study.
      Parents were given questions regarding their child's toilet training and
      behavior. Families were followed every 6 months during an office visit or by
      phone call until the child was successfully day time toilet trained. RESULTS: A
      total of 482 children (255 males) completed the study. There were 106 children
      (54 males) (22%) who experienced at least 1 month of stool toileting refusal.
      There was an association between the presence of younger siblings (P = .023) and
      parental inability to set limits for the child (P = .017) and stool toileting
      refusal. Stool toileting refusers trained at a later age than the rest of the
      group (P < .0001). Fifty percent (22/44) of the children who trained between 42
      and 48 months and 73% (8/11) of the children who trained after 48 months
      experienced stool toileting refusal. Sixty-one of the study children developed
      stool withholding during toilet training. Forty-nine (80%) of these children were
      stool toileting refusers (P < .00001). In 77 (73%) of the children no
      intervention was undertaken. Of these, the behavior lasted more than 6 months in
      20. Intervention was undertaken with 29 children, either because of severe stool
      withholding (23) or the age of the child (6). Interupting toilet training and
      having the child return to diapers resulted in the child spontaneously using the
      toilet for bowel movements within 3 months in 24 of 27 children. CONCLUSION:
      Stool toileting refusal occurred in one in five children in this study
      population. Two behaviors associated with stool toileting refusal may require the
      intervention of the pediatrician. The first is stool withholding causing
      constipation which can result in rectal impaction and primary encopresis. The
      second is lack of successful toilet training by 42 months of age. A child who is
      still untrained at this late age can be a source of family conflict and stress
      requiring the advice and support of the pediatrician.

PMID- 8989337
TI  - Behavioral characteristics of children with stool toileting refusal.
AB  - OBJECTIVE: To determine if children with stool toileting refusal have more
      behavior problems than matched children who are toilet trained. DESIGN: Case
      control study. SETTING: Suburban private pediatric practice. PARTICIPANTS:
      Children 30 to 48 months old who had achieved bladder control but refused to
      defecate on the toilet were identified as cases. Controls were sex- and age
      matched children who were fully toilet trained. MEASURES: Total behavior problems
      were assessed using a semi-structured behavior screening interview with the
      child's parents. The parents also completed the Child Behavior Checklist for ages
      2 to 4 and either the Toddler Temperament Scale (30 to 36 months old) or the
      Behavioral Style Questionnaire (36 to 48 months old). Child compliance with adult
      instructions was measured during a room clean-up task. RESULTS: Children with
      stool toileting refusal were not found to have more behavior problems than the
      matched children who were toilet trained. There were no differences between the
      two groups in compliance during the room clean-up task. There was a trend toward
      children with stool toileting refusal having a more difficult temperament, and
      these children were reported to have more problems with constipation and painful
      bowel movements than the controls. CONCLUSIONS: Children with stool toileting
      refusal do not have more behavior problems than controls who are toilet trained.
      Parents do report higher rates of constipation and painful defecation, but it is
      not clear whether this is a cause or effect of stool toileting refusal.

PMID- 8989339
TI  - Pediatric mortality probability estimated from pre-ICU severity of illness.
AB  - OBJECTIVE: The Pediatric Risk of Mortality (PRISM) score is a measure of illness
      severity based on abnormalities observed in the bedside examination and
      laboratory assessment. PRISM scores obtained after pediatric intensive care unit
      (PICU) admission predict mortality probability, but no previous efforts to
      evaluate mortality risk before PICU admission have been reported. Our study was
      performed on patients admitted to PICUs at four pediatric tertiary care centers
      to derive a quantitative estimate of hospital mortality probability as a function
      of PRISM scores obtained at referring hospitals before PICU transfer. Performance
      of the model was tested by evaluating accuracy of mortality predictions obtained
      from pre-ICU PRISM scores in a separate validation set of patients. METHODS:
      Patients were randomized to the derivation or validation sets. Data were recorded
      prospectively from observations made at hospitals referring to the study PICUs.
      Patients included 780 infants and children with medical and surgical emergencies
      and trauma. Electively admitted patients were excluded from analysis. RESULTS:
      The relationship between mortality probability (P) and the pre-ICU PRISM score is
      expressed by the equation: P = er/(1 + er). In this equation, r is an empirical
      function of the pre-ICU PRISM score: r = .197 x PRISM - 4.705. The mortality
      probability rises from near 0 at low scores, approaching 1 (certainty) above a
      PRISM score of 40. Mortality probability exceeds 10% at a score of 13 and exceeds
      50% at a score of 24. Performance of predictions in the validation set of
      patients was evaluated for five categories of mortality probability. The observed
      number of deaths corresponded to predicted mortality across the range of illness
      severity. When compared for each tertiary institution, observed mortality rates
      were similar to predictions for three of four institutions. For data obtained at
      institution D, the observed mortality of 17% significantly exceeded the 7%
      predicted rate. In infants younger than 1 year, as well as children 1 year and
      older, observed mortality rates were similar to predicted. CONCLUSIONS: The pre
      ICU PRISM score as a measure of illness severity provides an estimate of hospital
      mortality probability. Further investigation is required to determine the use of
      pre-ICU mortality estimates in making clinical decisions.

PMID- 8989340
TI  - Death in the intensive care nursery: physician practice of withdrawing and
      withholding life support.
AB  - OBJECTIVE: To determine the frequency of selective nontreatment of extremely
      premature, critically ill, or malformed infants among all infant deaths in a
      level III intensive care nursery (ICN) and to determine the reasons documented by
      neonatologists for their decisions to withdraw or withhold life support. METHODS:
      This was a descriptive study based on review of the medical records of all 165
      infants who died at a university-based level III ICN during 3 years. We
      determined whether each death had occurred despite the use of all available
      technologies to keep the infant alive or whether these were withheld or
      withdrawn, thereby leading to the infant's death. We also determined whether
      neonatologists documented either "futility" or "quality of life" as a reason to
      limit medical interventions. RESULTS: One hundred sixty-five infants died among
      the 1609 infants admitted during the study period. One hundred eight infant
      deaths followed the withdrawal of life support, 13 deaths followed the
      withholding of treatment, and 44 deaths occurred while infants continued to
      receive maximal life-sustaining treatment. For 90 (74%) of the 121 deaths
      attributable to withholding of withdrawal of treatment, physicians cited that
      death was imminent and treatment was futile. Quality-of-life concerns were cited
      by the neonatologists as reasons to limit treatment in 62 (51%). Quality of life
      was the only reason cited for limiting treatment for 28 (23%) of the 121 deaths
      attributable to withholding or withdrawal of treatment. CONCLUSIONS: The majority
      of deaths in the ICN occurred as a result of selective nontreatment by
      neonatologists, with few infants receiving maximal support until the actual time
      of death. Neonatologists often documented that quality-of-life concerns were
      considered in decisions to limit treatment; however, the majority of these
      decisions were based on their belief that treatment was futile. Prospective
      studies are needed to elucidate the determinants of neonatologists' practice
      decisions of selective nontreatment for marginally viable or damaged infants.

PMID- 8989341
TI  - Pulmonary effect of inhaled furosemide in ventilated infants with severe
      bronchopulmonary dysplasia.
AB  - BACKGROUND: When administered parenterally, furosemide, a loop diuretic, results
      in improved lung compliance and decreased airway resistance in infants with
      bronchopulmonary dysplasia (BPD). However, furosemide-induced diuresis results in
      hypokalemia, chloride deficiency, hypercalciuria, nephrocalcinosis, and rickets.
      In patients with asthma, inhaled furosemide has recently been demonstrated to
      inhibit the bronchoconstrictive effects of exercise, cold air hyperventilation,
      and antigen challenge. We hypothesized that inhaled furosemide will result in
      improved pulmonary mechanics in ventilated infants with BPD and will prevent the
      systemic complications of parenteral furosemide. OBJECTIVE: To determine the
      efficacy and safety of a single dose of inhaled furosemide on pulmonary mechanics
      in infants with severe BPD who are ventilator dependent at 21 days of age. DESIGN
      AND METHODS: A randomized, double-blind, crossover study was performed on 9
      infants with BPD, each serving as his own control. Each patient was randomized to
      receive an aerosol dose of furosemide (1 mg/kg in 2 mL of saline) or placebo (2
      mL of saline) on the first day of the study and the other agent the following day
      of the study. Pulmonary mechanics were measured before and 1 and 2 hours after
      the inhalation using the Pulmonary Evaluation and Diagnostics System. RESULTS:
      Gestational age (mean +/- SEM) was 29 +/- 1 weeks; birth weight was 1.1 +/- 0.1
      kg; age at study was 47 +/- 6 days; and weight at study was 1.8 +/- 0.2 kg. There
      was no significant change in the pulmonary function measurements before treatment
      and 1 or 2 hours after treatment with either placebo or furosemide. Baseline and
      2-hour values were: dynamic compliance (mL/ cm H2O per kilogram): 0.46 +/- .03 to
      0.50 +/- .03 (placebo) and 0.50 +/- 0.02 to 0.51 +/- 0.02 (furosemide); dynamic
      resistance (cm H2O/L per second): 118 +/- 9 to 106 +/- 7 (placebo) and 111 +/- 8
      to 105 +/- 7 (furosemide); and tidal volume (mL/kg): 8.6 +/- 0.5 to 8.9 +/- 0.5
      (placebo) and 8.9 +/- 0.2 to 9.4 +/- 0.3 (furosemide). CONCLUSION: We conclude
      that, under the conditions of our study, a single dose of 1 mg/kg inhaled
      furosemide does not improve the pulmonary mechanics in ventilator-dependent
      infants with severe BPD.

PMID- 8989342
TI  - Analgesia for dying infants whose life support is withdrawn or withheld.
AB  - OBJECTIVE: To determine the frequency of opiate analgesia administration to
      infants when life support is discontinued and to determine whether infant
      characteristics, such as birth weight and diagnosis, or the physician's reasons
      for discontinuing life support influence either the decision to provide opioid
      agents or the dosages administered. METHODS: We reviewed all 165 deaths in a 3
      year period at a university-based level III intensive care nursery. Of the 121
      deaths attributable to withdrawal or withholding of mechanical ventilation and/or
      extracorporeal membrane oxygenation, we ascertained whether opioid analgesics
      (morphine sulfate [MS] or fentanyl) were administered either concurrent with or
      after life-support withdrawal and at what doses. We examined whether these end-of
      life practices varied according to birth weight, diagnoses, and the reasons
      documented by the neonatologist for discontinuing life support. RESULTS: Opioid
      analgesia was provided to 84% of infants as their life support was either
      withheld or withdrawn. Infants with necrotizing enterocolitis and major anomalies
      or chromosomal disorders were more likely to be given opiates than infants with
      other diagnoses. Birth weight was not different for infants who received opiates
      compared with those who were not given opiates. Opioid analgesia was provided to
      all 18 infants for whom physicians documented the patients' suffering as a reason
      to discontinue life support. Sixty-four percent of infants who received opiates
      were given doses in the usual pharmacologic range of 0.1 to 0.2 mg/kg MS. Of the
      36 infants given more than 0.2 mg/kg MS, all but 2 were receiving ongoing
      treatment with opioid agents. CONCLUSIONS: In most cases of withholding or
      withdrawal of life support in critically ill infants, neonatologists provided
      opioid analgesia to these infants at the end of life, despite the potential
      respiratory depression of opioid agents in infants whose respiratory support is
      discontinued.

PMID- 8989343
TI  - Self-sufficiency at ages 27 to 33 years: factors present between birth and 18
      years that predict educational attainment among children born to inner-city
      families.
AB  - OBJECTIVES: Some inner-city infants grow to be successful, self-sufficient
      adults. This study is designed to identify characteristics from early childhood
      that foster or impede favorable outcomes and are useful for formulation of public
      policy. METHODS:  POPULATION: 2694 children (G-2s), born 1960 through 1965, to
      2307 inner-city women (G-1s) enrolled in the Johns Hopkins Collaborative
      Perinatal Study. DATA: 1) prospective observations (birth through 8 years) of
      neurologic and cognitive development, health, behavior, and family and
      neighborhood socioeconomic characteristics and 2) completed interviews with 1758
      G-2s (age 27 to 33) and 1552 G-1s, bridging the period from age 9 to present
      status. An intergenerational, life course model of development identified
      significant characteristics and events associated with G-2 outcome (education,
      physical and mental health, healthy lifestyle, and financial independence of
      public support, emphasizing educational attainment of a high school diploma or a
      graduate equivalency degree). Multiple logistic regression equations identified
      independent, predictive variables during infancy, preschool and early school
      years, and adolescence. The probability of a good outcome was estimated in the
      presence of combinations of the six variables most strongly associated with that
      outcome. RESULTS: Among G-2s, 79% had a successful outcome for education, 60%
      health, 70% lifestyle, and 76% for financial independence. Black G-2s had more
      favorable outcomes than white G-2s in education and lifestyle, whites for
      financial outcome; health did not differ by race. The six variables most
      predictive of adult education were: G-1 education at G-2 birth and G-2 attainment
      of honor roll, average or better reading skills at 8 years, avoidance of regular
      smoking, and pregnancy before age 18, and not repeating a grade in school.
      CONCLUSIONS: Substantial proportions of inner-city children become successful
      adults. Attention to improving public education, particularly language and
      reading skills, and the prevention of smoking and adolescent pregnancy are
      clearly indicated.

PMID- 8989344
TI  - Improving the vitamin K status of breastfeeding infants with maternal vitamin K
      supplements.
AB  - OBJECTIVE: To increase the phylloquinone (vitamin K1) concentration of human milk
      with maternal oral phylloquinone supplements such that both the phylloquinone
      intake of breastfed infants and their serum concentrations of phylloquinone would
      approach those of formula-fed infants who are known to be at much less risk for
      hemorrhagic disease of the newborn. DESIGN: Two stages: stage I, longitudinal,
      randomized study of 6 weeks' duration; and stage II, longitudinal, randomized,
      double-blind, placebo-controlled study of 12 weeks' duration. SETTING: Patients
      from a private pediatric practice in Madison, WI. PATIENTS: Stage I: sequential
      sampling of 20 lactating mothers to determine the level of maternal
      supplementation needed in stage II. Ten mothers received 2.5 mg/d oral
      phylloquinone, and 10 mothers received 5.0 mg/d oral phylloquinone. Stage II:
      sequential sampling of 22 human milk-fed infants and lactating mothers. All
      infants received 1 mg of phylloquinone at birth. Eleven mothers received a
      placebo; 11 mothers received 5 mg/d phylloquinone. MEASUREMENTS AND RESULTS: In
      stage I, both 2.5 and 5.0 mg/d phylloquinone significantly increased the
      phylloquinone content of human milk at both 2 and 6 weeks. As expected, 5.0 mg
      had a greater effect (mean +/- SD, 58.96 +/- 25.39 vs 27.12 +/- 12.18 ng/mL at 2
      weeks). In stage II, the vitamin K-supplemented group had significantly higher
      maternal serum phylloquinone concentrations, higher phylloquinone milk
      concentrations, and higher infant plasma phylloquinone concentrations at 2, 6,
      and 12 weeks compared with the placebo group. At 12 weeks infant phylloquinone
      intakes were significantly higher for the vitamin K group than the placebo group
      (9.37 +/- 4.55 vs 0.15 +/- 0.07 microgram/kg per day). This corresponded to a
      plasma phylloquinone concentration in the vitamin K group of 2.84 +/- 3.09 vs
      0.34 +/- 0.57 ng/mL in the placebo group. At 12 weeks, the prothrombin times did
      not differ between the groups, but the des-gamma-carboxy-prothrombin (partially
      carboxylated prothrombin thought to be a measure of vitamin K deficiency) was
      significantly elevated in the placebo group compared with the vitamin K group
      (1.48 +/- 1.19 vs 0.42 +/- 0.55 ng/mL). CONCLUSION: In exclusively breastfed
      infants who receive intramuscular phylloquinone at birth, the vitamin K status as
      measured by plasma phylloquinone and des-gamma-carboxy-prothrombin concentrations
      is improved by maternal oral supplements of 5 mg/d phylloquinone through the
      first 12 weeks of life.

PMID- 8989345
TI  - Reduction of respiratory syncytial virus hospitalization among premature infants
      and infants with bronchopulmonary dysplasia using respiratory syncytial virus
      immune globulin prophylaxis. The PREVENT Study Group.
AB  - OBJECTIVE: To determine the safety and efficacy of monthly prophylaxis with
      respiratory syncytial virus immune globulin, intravenous (RSV-IGIV) for reduction
      of the incidence of RSV-associated hospitalization. METHODS: A randomized, double
      blind, placebo-controlled clinical trial was conducted at 54 centers in the
      United States during the 1994 to 1995 RSV season. A total of 510 children with
      bronchopulmonary dysplasia and/or a history of prematurity were randomized to
      receive either 750 mg/kg RSV-IGIV (n = 250) or placebo (1% albumin; n = 260)
      intravenously every 30 days. Randomized groups were well balanced at entry for
      demographics, RSV risk factors, and birth characteristics. Children were
      monitored for adverse events and for RSV-associated hospitalization from
      randomization through 30 days after the last infusion visit; serious adverse
      events were monitored for an additional 30 days. For children hospitalized with
      RSV, data were collected regarding the total days of RSV stay, total days of
      increased oxygen requirement, total days with a moderate or severe lower
      respiratory tract illness, and frequency and duration of intensive care unit stay
      and mechanical ventilation. Ninety-five percent of participants completed the
      protocol and 85% received a complete course of infusions. RESULTS: The incidence
      of RSV hospitalization was reduced by 41% in children receiving RSV-IGIV
      prophylaxis; 35 (13.5%) of the children in the placebo group were hospitalized
      for RSV, compared with 20 (8.0%) RSV-IGIV recipients. RSV-IGIV recipients had a
      53% reduction in the total number of RSV hospital days per 100 children, a 60%
      reduction in the number of RSV days with increased oxygen requirement, and a 54%
      reduction in the number of RSV hospital days with a moderate or severe lower
      respiratory tract illness. In addition, children receiving RSV-IGIV had a 38%
      reduction in hospitalization for respiratory illness of any cause and a 46%
      reduction in total hospital days for respiratory illness per 100 children. RSV
      IGIV was safe and well tolerated, with a safety profile similar to other IGIV
      preparations. Between 1% to 3% of children had medically significant adverse
      events related to RSV-IGIV administration. CONCLUSIONS: Monthly administration of
      750 mg/kg of RSV-IGIV was safe and well tolerated and was effective in reducing
      the incidence and total days of both RSV hospitalization and overall respiratory
      hospitalization in infants with a history of prematurity or bronchopulmonary
      dysplasia or both.

PMID- 8989346
TI  - Clinical practice guidelines in pediatric and newborn medicine: implications for
      their use in practice.
AB  - Clinical practice guidelines are becoming pervasive in pediatrics and newborn
      medicine. They have spanned a wide range of primary care practice parameters from
      treating otitis media with effusion, to performing complex surgery for congenital
      heart disease, and management of respiratory distress syndrome and coordinating
      discharge from the neonatal intensive care unit. Administrators believe that
      using clinical practice parameters reduces health care costs, improves quality of
      care, and limits malpractice liability. Practice parameters and guidelines have
      grown in use because powerful interests-third-party payers, insurers, and health
      maintenance organizations, as well as hospital administrators bent on reducing
      variable costs of care and contracting for capitated care-champion their
      development, implementation, and monitoring. Economic credentialing of physicians
      with excessive variances without risk-adjusting for other than average patients
      is problematic and remains unchecked partly because of the fundamental
      characteristics of the evolving health care industry in which costs are more
      easily measured than quality. For highly autonomus physicians this
      standardization of medical decision making may represent a difficult transition
      into corporate practice by realigning traditional values of the doctor-patient
      relationship. However, because guidelines are almost certainly here to stay,
      pediatricians and neonatologists need to think critically about how their content
      and method of implementation, monitoring, and modification may influence medical
      teaching and decision making in the future. If guidelines are introduced
      primarily as a cost savings or containment tool that ignores the impact on the
      quality of care and restricts necessary care for infants and children, especially
      those with chronic illness or who are developmentally at risk, then
      neonatologists and pediatricians must be quick and determined to challenge the
      potentially damaging use of practice parameters or guidelines. Furthermore, there
      are many medicolegal implications of guideline implementation that may not favor
      physicians and leave to hospitals, insurers, and ultimately the courts decisions
      regarding evidence-based practice. In this review article, we pay special
      attention to the guidelines developed in newborn medicine. We discuss why and how
      guidelines are developed and critically evaluate the available evidence
      describing potential benefits and drawbacks of guidelines in general. There are
      legal implications to the implementation of guidelines, and guidelines may
      increase provider susceptibility to malpractice allegations. Neonatologists and
      pediatricians should critically analyze the following questions when guidelines
      are being developed: Are clinical practice parameters the most effective means to
      reduce the costs of health care, or improve the quality of health care services
      while reducing the need for and protecting physicians from malpractice suits? Or
      do clinical practice guidelines more closely resemble an audit system developed
      by health care organizations, insurers, and others including government-sponsored
      health care to appease powerful interests-with limited evidence for promise and
      perhaps potential negative cost, quality, and malpractice liability implications?
      In pediatric and newborn medicine there is limited evidence that guidelines have
      achieved the desired goals and further analysis of their process of care and the
      costs of implementation is warranted.

PMID- 8989347
TI  - Wrong turns in sudden infant death syndrome research.

PMID- 8989349
TI  - The pediatrician's role in disaster preparedness. American Academy of Pediatrics
      Committee on Pediatric Emergency Medicine.

PMID- 8989348
TI  - Considerations related to the use of recombinant human growth hormone in
      children. American Academy of Pediatrics Committee on Drugs and Committee on
      Bioethics.
AB  - Since 1985 molecular biology techniques have made possible the synthetic
      synthesis of pure human growth hormone in potentially unlimited amounts. With
      this increased availability, its use in patients other than children with growth
      hormone deficiency has been associated with clinical and ethical questions. This
      statement presents an analysis of the current status of the use of human growth
      hormone in children.

PMID- 8989350
TI  - Participation in boxing by children, adolescents, and young adults. American
      Academy of Pediatrics Committee on Sports Medicine and Fitness.
AB  - Because boxing may result in serious brain and eye injuries, the American Academy
      of Pediatrics opposes this sport. This policy statement summarizes the reasons.

PMID- 8989351
TI  - Recommended childhood immunization schedule--United States, January-December
      1997. American Academy of Pediatrics Committee on Infectious Diseases.

PMID- 8989352
TI  - Guidelines for the pediatric cancer center and role of such centers in diagnosis
      and treatment. American Academy of Pediatrics Section Statement Section on
      Hematology/Oncology.
AB  - The intent of this statement is to delineate those personnel and facilities that
      are essential to provide state-of-the-art care for children and adolescents with
      cancer. This statement emphasizes the importance of a board-eligible or board
      certified pediatric hematologist-oncologist and pediatric subspecialty
      consultants overseeing the care of all pediatric and adolescent cancer patients,
      and the need for facilities available only at a tertiary center as essential for
      the initial management and much of the follow-up for pediatric and adolescent
      cancer patients. In 1986, the Section on Oncology/Hematology of the American
      Academy of Pediatrics outlined the "Guidelines for the Pediatric Cancer Center
      and Role of Such Centers in Diagnosis and Treatment." Since that statement was
      published, significant changes in medical care reimbursement have prompted a
      review of the role of tertiary medical centers in the care of pediatric patients.
      The potential impact of these developments on the treatment of children with
      cancer led to a revision of the previous statement with the goal of delineating
      those elements that are necessary to ensure that current childhood cancer
      survival rates are not adversely impacted by requirements for care to be given at
      sites lacking essential personnel or equipment.

PMID- 8989353
TI  - Radiation exposure of very low birth weight (< 1500-g) infants.

PMID- 8989354
TI  - Questions on the practice parameter--gastroenteritis.

PMID- 8989355
TI  - Questions on the practice parameter--gastroenteritis.

PMID- 8989356
TI  - Vaccine injury--no reports.

PMID- 8989357
TI  - Prenatal information of lungs and bronchopulmonary dysplasia.

PMID- 8989358
TI  - Vaccine-associated paralytic poliomyelitis.

PMID- 8989359
TI  - Health supervision for children with Turner syndrome.

PMID- 8989361
TI  - Health supervision for children with Turner syndrome.

PMID- 8989360
TI  - Health supervision for children with Turner syndrome.

PMID- 8989362
TI  - Health supervision for children with Turner syndrome.

PMID- 8989364
TI  - Inhibition of DNA synthesis and G1/S-phase transition in normal human fibroblasts
      elicited by a heat-labile trans-acting factor in gamma-irradiated HeLa cell
      extracts.
AB  - Proliferating human cells exposed to ionizing radiation show complex cellular
      responses including a delay in progression through various phases in the cell
      cycle. These cell cycle checkpoints are regulated by mitogenic signaling pathways
      which transduce the extracellular signals to the cell cycle control machinery. In
      this study we demonstrate that microinjection of a cellular extract, prepared
      from gamma-irradiated (40 Gy) HeLa cells, into the cytoplasm of normal human
      fibroblasts results in suppression of DNA replicative synthesis, indicating the
      presence of a trans-acting DNA synthesis-inhibiting factor(s). The addition of
      this same extract to the culture medium for a short time (< or = 2 h) also
      inhibits DNA synthesis in human fibroblasts, affecting both replicon initiation
      and DNA chain elongation processes. Moreover, a 2-h incubation of the fibroblast
      cultures with the extract causes a transient delay in cell progression from G1 to
      S phase coupled with up-regulation of the p53 tumor suppressor protein. Both the
      DNA synthesis-inhibiting and G1-phase-blocking activities are reduced markedly
      when the extract is heated (80 degrees C; 10 min) prior to its addition to the
      culture medium. On the other hand, pretreatment of the fibroblast cultures with
      KN62, an inhibitor of calmodulin-dependent kinase II (CaMKII), serves to abrogate
      the inhibitory effect of the extract on DNA synthesis without influencing its
      ability to induce the G1-phase block. These results are compatible with the
      presence in HeLa cell extracts of a heat-labile trans-acting factor that
      triggers, in normal human cells, the activation of (1) a CaMKII-dependent signal
      transduction pathway mediating suppression of DNA synthesis and (2) a p53
      dependent pathway mediating G1-phase checkpoint control.

PMID- 8989363
TI  - Spatial and temporal patterns of expression of epidermal growth factor,
      transforming growth factor alpha and transforming growth factor beta 1-3 and
      their receptors in mouse jejunum after radiation treatment.
AB  - The goal of the present study was to assess changes in proliferation in the mouse
      jejunum after irradiation and the role of the growth factors EGF, TGF-alpha and
      TGF-beta 1-3 in the proliferative response. Our working hypothesis was that
      feedback signals from the villus to cells in the crypt regulate proliferation,
      and that the growth factors EGF and TGF-alpha with their common receptor EGF-R
      are involved in stimulation of proliferation, while the growth factors TGF-beta 1
      3 with their receptors TGF-beta RI and TGF-beta RII are involved in inhibition of
      proliferation during this regulation. Immunohistochemical detection methods and
      automated image analysis were used for objective quantification of growth factor
      expression. The data indicate that, after 5 Gy irradiation, growth stimulation in
      the crypts takes place before major changes in the villi are observed. However,
      the combination of the reduction in the cell number, the number of cells
      expressing TGF-beta 1-3 and the reduction in the level of expression of TGF-beta
      1-3 in the villi may cause the release of crypt cells from regulatory growth
      inhibition and initiate a proliferation-stimulating signal by an increase in the
      production of TGF-alpha and EGF. Regulation of proliferation after initiation of
      a proliferative response seems to be related more to the growth factors EGF, TGF
      alpha and TGF-beta 3 in the crypts than to villus cellularity or growth factor
      expression, supporting the concept of stem cell autoregulation as a mechanism of
      cell regeneration in the intestinal crypt.

PMID- 8989365
TI  - Genomic instability in Chinese hamster cells after exposure to X rays or alpha
      particles of different mean linear energy transfer.
AB  - Evidence has accumulated that radiation induces a transmissible persistent
      destabilization of the genome, which may result in effects arising in the progeny
      of irradiated but surviving cells. An enhanced death rate among the progeny of
      cells surviving irradiation persists for many generations in the form of a
      reduced plating efficiency. Such delayed reproductive death is correlated with an
      increased occurrence of micronuclei. Since it has been suggested that radiation
      induced chromosomal instability might depend on the radiation quality, we
      investigated the effects of alpha particles of different LET by looking at the
      frequency of delayed micronuclei in Chinese hamster V79 cells after cytochalasin
      induced block of cell division. A dose-dependent increase in the frequency of
      micronuclei was found in cells assayed 1 week postirradiation or later. Also,
      there was a persistent increase in the frequency of dicentrics in surviving
      irradiated cells. Moreover, we found an increased micronucleus frequency in all
      of the 30 clones isolated from individual cells which had been irradiated with
      doses equivalent to either one, two or three alpha-particle traversals per cell
      nucleus. We conclude that the target for genomic instability in Chinese hamster
      cells must be larger than the cell nucleus.

PMID- 8989366
TI  - Correlation of radiation-induced micronucleus frequency with clonogenic survival
      in cells of one diploid and two tetraploid murine tumor cell lines of the same
      origin.
AB  - Whether the micronucleus assay can be used as a predictive tool to estimate the
      intrinsic cellular radiosensitivity depends on whether the results correlate with
      clonogenic survival. In the present study we investigated the influence of the
      ploidy on the correlation of the two assays by comparing cells of one diploid and
      two tetraploid murine tumor cell lines of different radiosensitivities. A
      definite correlation between survival and micronucleus frequency is evident for
      all three cell lines investigated. The rank order of the frequency of
      micronucleus expression correlates with that of clonogenic survival in the cell
      lines studied. No influence of DNA content on the radiosensitivity and the
      relationship between the micronucleus frequency and clonogenic survival could be
      observed. Thus our results are promising for the clinical application of the
      micronucleus assay as a predictive measure of radiosensitivity. However, it is
      necessary to consider such factors such as cell proliferation kinetics which may
      influence the correlation between micronucleus frequency and clonogenic survival.

PMID- 8989367
TI  - An assay for quantifying DNA double-strand break repair that is suitable for
      small numbers of unlabeled cells.
AB  - A system based on pulsed-field gel electrophoresis (PFGE) is described which
      measures the induction and repair of DNA double-strand breaks (DSBs) in a
      biologically relevant X-ray dose range (below 10 Gy) using as few as 125 cells
      per time. This system was used to measure repair in cells of a freshly obtained
      human glioblastoma multiforme tumor. No prelabeling of the cells is required, and
      many different cell types can be studied using this system. Under the pulsed
      field conditions used, DNA in the range of 2 to 6 Mb enters the PFGE gel and
      forms an upper compression zone directly under each well. To quantify the DSBs
      after electrophoresis, the DNA was transferred to nylon membranes and hybridized
      with 32P-labeled chromosomal DNA. Phosphor screens were exposed to the membranes
      and scanned on a phosphor imager. The kinetics of induction and repair was
      determine by measuring the amount of DNA in the compression zones compared to the
      amount in the wells. EMT-6 cells were used to demonstrate this method. Induction
      of DSBs by doses of 0-7.5 Gy X rays was assayed using approximately 12,500 cells
      per dose and was shown to be linear. Double-strand breaks from 1 Gy were detected
      above background. To determine a lower limit of the number of cells that could be
      used to measure DSB repair, cells were embedded in agarose at decreasing
      concentrations per plug, exposed to 7.5 Gy X irradiation and allowed to repair at
      37 degrees C for up to 60 min. DNA from approximately 12,500, 1,250 and 125 cells
      per time was loaded and subjected to PFGE. The average fast-repair half-time was
      3 min and the slow-repair half-time was 35 min. The kinetics of DSB repair in
      glioblastoma multiforme cells was also determined using this system. Agarose
      plugs were prepared from a cell suspension, irradiated with 7.5 Gy X rays and
      allowed to repair for up to 90 min. DNA from approximately 1,250 tumor cells was
      electrophoresed and analyzed as described above for EMT-6 cells. For this
      particular tumor, approximately 75% of the induced DSBs were repaired after 90
      min. Data presented show that this PFGE-based system is an extremely sensitive
      method for measuring DSB induction and repair after low doses of X rays using
      very few cells.

PMID- 8989368
TI  - Sialyl Lewis X mimetics attenuate E-selectin-mediated adhesion of leukocytes to
      irradiated human endothelial cells.
AB  - Ionizing radiation causes histological changes in normal tissues that resemble
      those resulting from the inflammatory response. Inflammation is a multistep
      process requiring expression of adhesion molecules on the surface of endothelial
      cells which results in leukocyte extravasation. E-selectin is an adhesion
      molecule that mediates leukocyte "rolling" on the endothelium and is required for
      the inflammatory response. We quantified E-selectin expression and selectin
      dependent adhesion of leukocytes to human endothelial cells after X irradiation
      to determine whether E-selectin participates in the radiation-mediated
      inflammation-like response. Immunofluorescence staining of irradiated endothelial
      cells demonstrated expression of E-selectin on the cell surface similar to that
      elicited by treatment with interleukin-1 (IL-1). Radiation-mediated expression of
      E-selectin was dependent on dose and time and occurred at doses as low as 0.5 Gy.
      Furthermore, the increased adhesion of leukocytes to irradiated endothelial cells
      was prevented by an E-selectin-blocking antibody. Sialyl Lewis X is one of the
      molecules on the surface of leukocytes that adheres to E-selectin. The anti
      inflammatory agents glycyrrhizin and carminic acid, which are structural
      analogues of sialyl Lewis X, attenuated adhesion of leukocytes to endothelial
      cells treated with X rays or IL-1. These data implicate a new class of anti
      inflammatory agents in the prevention of adhesions of leukocytes to the
      irradiated vascular endothelium.

PMID- 8989369
TI  - Delayed repair of DNA damage by ionizing radiation in cells from patients with
      juvenile systemic lupus erythematosus and rheumatoid arthritis.
AB  - We used a single-cell alkaline gel electrophoresis (SCAGE) assay to study repair
      of primarily single-stranded DNA breaks after in vitro exposure to ionizing
      radiation in cells from children with systemic lupus erythematosus (SLE),
      juvenile rheumatoid arthritis (JRA), systemic sclerosis (SSc) and
      dermatomyositis. Peripheral blood lymphocytes from patients with SLE, JRA and SSc
      had significantly greater DNA damage after irradiation with 1.5 Gy and 30 min
      incubation (i.e. repair time) than did those from controls, as assessed by the
      length of the migrating DNA comet. The mean comet tail lengths were: SLE, 42
      microns; JRA, 40 microns; and SSc, 36 microns. Each of these was significantly
      different from controls, which had a mean comet tail length of 18 microns (P <
      0.001, < 0.001 and < 0.05, respectively). Cells from patients with
      dermatomyositis had an average comet tail length of 22 microns and were not
      significantly different from controls. Understanding the etiology of the delay in
      DNA repair in these diseases may provide insight into disease pathogenesis.

PMID- 8989370
TI  - A versatile and rapid assay of radiosensitivity of peripheral blood leukocytes
      based on DNA and surface-marker assessment of cytotoxicity.
AB  - We describe a rapid assay to predict intrinsic radiosensitivity of normal tissues
      based on the radiation-induced cytotoxic response of a number of types of white
      blood cells. Twenty-four hours after irradiation, leukocytes were prepared for
      analysis by flow cytometry. Radiation-induced cytotoxicity was characterized by
      degradation of internucleosomal DNA, which results in a reduced G1/G0-phase DNA
      peak. Clear differences in the radiosensitivity of five of six different types of
      leukocytes were observed. Significant increases in cytotoxicity were observed
      even at 0.5 Gy, indicating the technique may be useful as a biological dosimeter
      after radiation accidents. Based on data from 12 healthy blood donors,
      significant inter-donor differences in radiosensitivity were observed after
      exposure to 2 or 8 Gy of high-dose-rate X rays. Inter-donor variation was
      significantly greater than intra-donor variation for both CD4 and CD8 T
      lymphocytes (P < 0.01), and the technique yielded adequate data to stratify
      donors based on the radiosensitivities of these two cell types alone, requiring
      less than 1 ml of blood. The assay is a general assay of early cytotoxic response
      to radiation-induced damage and should be useful when assaying the response to
      chemotherapy as well.

PMID- 8989371
TI  - Effects of recombinant cytokines on colony formation by irradiated human cord
      blood CD34+ hematopoietic progenitor cells.
AB  - The role of recombinant hematopoietic growth factors in radiation repair has
      become a subject of increasing interest in both clinical and basic radiobiology.
      Combinations of cytokines such as hepatocyte growth factor, interleukin (IL)-3,
      IL-11, kit ligand, GM-CSF and erythropoietin were used to study the in vitro
      radiation dose response of human cord blood CD34+ hematopoietic progenitor cells
      using clonogenic survival assays. CD34+ cells were isolated by immunomagnetic
      selection and irradiated at 8 cGy/min. Irradiated cells were plated in
      methylcellulose with or without added cytokines, and hematopoietic colonies
      including CFU-GM, BFU-E and CFU-GEMM were scored on day 14. The radiation
      response characteristics of BFU-E and CFU-GEMM were similar for all culture
      conditions tested. The D0 values for BFU-E ranged between 1.29 and 2.40 Gy and n
      between 1.0 and 1.4. The D0 values for CFU-GEMM ranged from 86 cGy to 2.02 Gy and
      n between 1.0 and 1.5. The D0 for CFU-GM grown without added factors was 1.03 Gy.
      With single cytokine stimulation (IL-3, IL-11 or varying concentrations of HGF),
      D0 values ranged from 1.11 to 1.44 Gy. With the combination of IL-3, GM-CSF, kit
      ligand and HGF, D0 values were not significantly altered and ranged between 1.61
      and 2.60 Gy. In contrast, the combination of IL-11 and HGF produced an increase
      in the shoulder of the radiation survival curve (n = 3.35). No increase in the
      shoulder was detected for any of the other conditions tested (n = 1.0-1.7). Thus
      the combination of HGF and IL-11 increased the radiation survival of
      hematopoietic progenitor cells forming CFU-GM. Understanding the mechanism by
      which combinations of early-acting growth factors support postirradiation
      recovery of primitive clonogenic hematopoietic cells may be relevant to the
      design of clinical protocols for improving hematopoietic recovery after total
      body irradiation.

PMID- 8989372
TI  - Radiation chemistry of physiological saline reinvestigated: evidence that
      chloride-derived intermediates play a key role in cytotoxicity.
AB  - Contrary to common belief, hydrogen peroxide (H2O2) and hypochlorite (HOCl) are
      not produced continuously and independently during the irradiation of buffer
      solution containing chloride. Different buildup and decay reactions are involved
      in a complex interaction of these substances during irradiation. Which of the
      species predominates is determined by the parameters of the solution. The amount
      of either compound detectable after irradiation depends on the dissolved gas (O2,
      N2O or N2), on the pH value and to some extent on the presence of catalytic
      metals: Under slightly acidic conditions, low oxygen content and high generation
      rates of OH radicals, the only detectable species is hypochlorite; at high oxygen
      content and at pH values in the physiological range, hydrogen peroxide is the
      main detectable product. However, H2O2 and HOCl react with each other in a pH
      dependent way, yielding the stable products O2 and Cl-. This reaction limits the
      expected lifetime of both species in aqueous solution to some tens of seconds.
      Therefore, analysis of the sample solution after irradiation determines only the
      substance that was present in greater relative concentration at the termination
      of irradiation. Such analysis, however, does not allow conclusions about the
      processes that occurred during irradiation. We have investigated the decay and
      formation reactions of H2O2 and HOCl under all relevant irradiation conditions
      and found evidence that the formation and further reaction of HOCl-, the
      precursor of HOCl, is of central importance even in cases where no significant
      amounts of H2O2 or HOCl are detectable after irradiation. We discuss the
      consequences of these results for the cytotoxicity observed after irradiation of
      cells suspended in physiological saline and conclude that analogous processes
      must also be relevant for irradiations under in vivo conditions.

PMID- 8989373
TI  - Irradiation of mixed beam and design of spread-out Bragg peak for heavy-ion
      radiotherapy.
AB  - Data on cellular inactivation resulting from mixed irradiation with charged
      particle beams of different linear energy transfer (LET) are needed to design a
      spread-out Bragg peak (SOBP) for heavy-ion radiotherapy. The present study was
      designed to study the relationship between the physical (LET) and biological
      (cell killing) properties by using different monoenergetic beams of 3He, 4He and
      12C ions (12 and 18.5 MeV/nucleon) and to attempt to apply the experimental data
      in the design of the SOBP (3 cm width) with a 135 MeV/nucleon carbon beam.
      Experimental studies of the physical and biological measurements using
      sequentially combined irradiation were carried out to establish a close
      relationship between LET and cell inactivation. The results indicated that the
      dose-cell survival relationship for the combined high- and low-LET beams could be
      described by a linear-quadratic (LQ) model, in which new coefficients alpha and
      beta for the combined irradiation were obtained in terms of dose-averaged alpha
      and square root of beta for the single irradiation with monoenergetic beams.
      Based on the relationship obtained, the actual SOBP designed for giving a uniform
      biological effect at 3 cm depth was tested with the 135 MeV/nucleon carbon beam.
      The results of measurements of both physical (LET) and biological (90% level of
      cell killing, etc.) properties clearly demonstrated that the SOBP successfully
      and satisfactorily retained its high dose localization and uniform depth
      distribution of the biological effect. Based on the application of these results,
      more useful refinement and development can be expected for the heavy-ion
      radiotherapy currently under way at the National Institute of Radiological
      Sciences, Japan.

PMID- 8989374
TI  - Changes in in vivo optical properties and light distributions in normal canine
      prostate during photodynamic therapy.
AB  - The optical absorption and transport scattering coefficients of normal prostate
      tissue have been measured in vivo in dogs. The measurements were made at 630 nm
      before and during treatment by Photofin photodynamic therapy using interstitial
      optical fiber fluence-rate detectors. Corresponding measurements were made ex
      vivo, at 1 week after treatment, in the contralateral lobe. The optical
      properties were derived by applying a diffusion theory model to the fluence rates
      measured at two different source-detector fiber distances. While the in vivo
      pretreatment and in vivo contralateral post-treatment absorption and scattering
      values are self-consistent and in agreement with published data, significant
      changes were observed in the light fluence rates, and hence in the derived
      optical properties, during light irradiation. The possible causes of such changes
      are considered, and the implications for light dosimetry in photodynamic therapy
      are discussed.

PMID- 8989375
TI  - Biological effects of inhaled 144CeCl3 in beagle dogs.
AB  - The biological effects of 144Ce were studied in beagle dogs that were exposed to
      graded activity levels of 144CeCl3 via a single, brief inhalation exposure and
      observed for their life span. The long-term retained body burdens ranged from
      0.06 to 13 MBq/kg with a median of 1.2 MBq/kg. After a short residence time in
      the lung, most of the 144Ce was translocated to liver and skeleton, where the
      144Ce was retained with a half-time approaching the physical half-life of 144Ce,
      284 days. Significant radiation doses were delivered to the lung, 28 Gy (median)
      and 2.5-370 Gy (range); liver, 68 Gy (median) and 6.1-250 Gy (range); and
      skeleton, 21 Gy (median) and 1.9-100 Gy (range). Lesions induced by the beta
      particle radiation were noted in the lung, liver, skeleton, bone marrow, and oral
      and nasal mucosae closely associated with bone. Early deaths (within 2.5 years)
      were generally related to hematological dyscrasia, radiation pneumonitis, or
      hepatocellular degeneration and atrophy. Neoplasms that occurred relatively
      early, from 2.2-6.8 years after exposure, were noted in the liver, bone, bone
      marrow and oral mucosa closely associated with bone. Neoplasms that occurred
      later, beyond 7 years after exposure, were noted in the liver, lung and nasal
      mucosa closely associated with bone. Increased numbers of neoplasms were not
      found in two other organs that had relatively high radiation doses, namely the
      thyroid and kidney. Only one primary bone tumor was noted, but 11 tumors of bone
      associated tissues (oral and nasal mucosae and bone marrow) were found. Radiation
      doses and effects in tissues adjacent to bone, especially those of epithelial or
      marrow origin, should be considered when determining risks from internally
      deposited bone-seeking radionuclides, such as 144Ce. The property of 144Ce in
      depositing on and remaining associated with bone surfaces for long times may be
      an important factor in the radiation dose to bone marrow and epithelium adjacent
      to bone.

PMID- 8989376
TI  - Somatic mutation frequencies in Tradescantia stamen hairs treated with relatively
      low thermal neutron fluxes.
AB  - Young inflorescence-bearing cuttings of Tradescantia clone BNL 02, a blue/pink
      heterozygote, were treated with thermal neutrons for 12-120 s in the Irradiation
      Tube set in the Heavy Water Facility of the KUR Reactor of the Research Reactor
      Institute, Kyoto University. In this facility, practically all components of the
      neutron flux were thermal neutrons. The thermal neutron fluxes measured
      simultaneously with gold foils were 2.90-33.3 x 10(10) nth cm-2, and the gamma
      ray contamination per 10(10) nth cm-2 was 2.58 x 10(-4) C/kg (1.0 R). The induced
      somatic pink mutation frequencies in the stamen hairs increased linearly with
      thermal neutron flux at a rate of 1.69 pink mutant events per 10(4) hair-cell
      divisions per 10(10) nth cm-2 in Experiments 1 and 2, but at a higher rate of
      3.87 pink mutant events per 10(4) hair-cell divisions per 10(10) nth cm-2 in
      Experiment 3. The relatively small thermal neutron fluxes applied were calculated
      to have resulted in absorbed doses of 16.8-193 mGy, and the absorbed doses of
      contaminating gamma rays were 28.0-321 mGy. Therefore, these mutation frequencies
      could be converted into 109 and 251 pink mutant events per 10(4) hair-cell
      divisions per gray, including the contaminating gamma rays, and were 2.14-4.92
      times higher than the 51.0 pink mutant events per 10(4) hair-cell divisions per
      gray for relatively small doses of acute X rays which was obtained in earlier
      studies. The relative biological effectiveness of heavy particles (p, alpha and
      7Li) produced by thermal neutrons was calculated to be between 11.0 and 35.4
      compared with acute X rays rather than with 18-20-h exposure to gamma rays, the
      value of 11.0 being considered to be more reliable.

PMID- 8989377
TI  - Nutrient dilution before and after X irradiation increases the radioresistance of
      log- and plateau-phase Chinese hamster V79 cells.
AB  - Previous observations have shown that cells cultured in standard growth medium
      (100%) demonstrated similarly enhanced survival when incubated postirradiation
      either in non-growth-promoting conditioned medium or in growth-promoting 40%
      growth medium (Reddy and Lange, Radiat, Res. 119, 338-347, 1989). From these
      results, it was suggested that nutrient dilution altered radiosensitivity by a
      mechanism independent of progression of cells through the cell cycle. In this
      study, we have examined the effects on radiosensitivity of incubation in 40%
      growth medium prior to irradiation on both log- and plateau-phase Chinese hamster
      V79 cells and the effects on the distribution of cells in the cell cycle of
      incubation in 40% or 100% growth medium before and after irradiation.
      Radioresistance increased by a factor of 1.5-1.6 compared to 100% growth medium
      for both log-phase and plateau-phase cells cultured in 40% growth medium prior to
      X irradiation and incubated in either 40% growth medium or conditioned medium
      after X irradiation. The cell cycle distributions of log-phase cells in 100% and
      40% growth medium before irradiation were identical. The change in cell cycle
      distribution induced by 10 Gy did not differ among log-phase cells incubated for
      3 h postirradiation in 100% growth medium, 40% growth medium or conditioned
      medium. These results, in addition to supporting our previous conclusions,
      demonstrate that culturing prior to irradiation in 40% growth medium alone
      increases cell survival and that incubation in 40% growth medium before and after
      irradiation maximizes the survival of V79 cells.

PMID- 8989378
TI  - Organizing principles for voluntary movement: extending single-joint rules.
AB  - 1. Four subjects performed fast flexions of the elbow or shoulder over three
      different distances. Elbow flexions were performed both in a horizontal, single
      degree-of-freedom manipulandum and in a sagittal plane with the limb
      unconstrained. Shoulder flexions were only performed in the sagittal plane by the
      unconstrained limb. We simultaneously recorded kinematic and electromyographic
      (EMG) patterns at the "focal" joint, that which the subject intentionally flexed,
      and at the other, "nonfocal" joint that the subject had been instructed to not
      flex. 2. Comparisons of the elbow EMG patterns across tasks show that agonist and
      antagonist muscles were similar in pattern but not size, reflecting the net
      muscle torque patterns. Comparisons at the shoulder also revealed similar EMG
      patterns across tasks that reflected net muscle torques. 3. Comparisons of EMG
      patterns across joints show that elbow and shoulder flexors behaved similarly.
      This was not true of the extensors. The triceps EMG burst was delayed for longer
      distances but the posterior deltoid had an early, distance-invariant onset. 4.
      Similarities in EMG reflect torque demands required at the focal joint to produce
      flexion and at the nonfocal joint to reduce extension induced by dynamic
      interactions with the focal, flexing joint. These similarities appear despite
      very different kinematic intentions and outcomes. This argues against a strong
      role for length-sensitive reflexes in their generation. 5. These results support
      the hypothesis that movements are controlled by muscle activation patterns that
      are planned for the expected torque requirements of the task. This general rule
      is true whether we are performing single-joint or multiple-joint movements, with
      or without external constraints. The similarities between single-joint and
      multijoint movement control may be a consequence of ontogenetic development of
      multijoint movement strategies that prove useful and are therefore also expressed
      under the constrained conditions of specialized tasks such as those performed in
      single-joint manipulanda.

PMID- 8989379
TI  - Mechanisms underlying direction selectivity of neurons in the primary visual
      cortex of the macaque.
AB  - 1. We studied the effects of blocking intracortical inhibition by
      microiontophoretic administration of bicuculline methiodide (BMI), a selective
      antagonist for gamma-aminobutyric acid-A receptors, on direction sensitivity of
      103 neurons in the primary visual cortex (VI) of anesthetized and paralyzed
      monkeys. 2. The direction selectivity index (DSI) of each cell was calculated for
      the control response and response during the BMI administration at the optimal
      stimulus orientation to assess the directionality of an individual cell. 3. The
      averaged direction tuning of visual responses of cells was sharp in layers IVa
      and IVb, moderate in both interblob and blob regions of layer II/III and layers V
      and VI, and poor in layers IVc alpha and IVc beta. 4. Iontophoretic
      administration of BMI uncovered or facilitated responses to stimuli moving in the
      nonpreferred direction, and reduced DSIs of cells to a varying extent in all the
      layers except layer VI. Responses to stimuli moving in the preferred direction
      were also facilitated so that a slight bias of response toward the originally
      preferred direction remained during BMI administration in most cells. 5. Most of
      the cells in layers II/III (both blobs and interblobs) and IVb that receive
      inputs from layers IVc alpha and IVc beta showed a clear reduction of direction
      selectivity during BMI administration. This result suggests that intracortical
      inhibition plays an important role in the elaboration of direction selectivity at
      the second stage of information processing in VI. 6. The direction selectivity of
      cells in layer VI was most resistant to the effects of BMI, suggesting that it is
      dependent on excitatory inputs that are already direction selective, even though
      the sample size of this layer was small. 7. In direction-selective cells outside
      layer VI, responses to a stimulus moving in the preferred direction were enhanced
      in a way that was linearly related with those in the nonpreferred direction as
      the BMI dose was increased. This suggests that various amounts of inhibition
      interact linearly with directionally biased excitatory inputs to raise the firing
      threshold to various levels so as to produce various degrees of directionality.
      8. These results suggest that, in most of the directionally sensitive cells
      except for those in layer VI, there are excitatory inputs which are bidirectional
      but slightly biased to one direction, and that the intracortical inhibition
      raises a threshold level of responses to excitatory inputs so that the response
      become direction selective.

PMID- 8989380
TI  - Frequency-dependent propagation of sodium action potentials in dendrites of
      hippocampal CA1 pyramidal neurons.
AB  - 1. The propagation of antidromically activated action potentials in CA1 pyramidal
      neurons was examined with intrasomatic and intradendritic electrical recording
      and optical measurements using the fluorescent calcium indicator Calcium Green-1.
      2. In somatic recordings, trains of 40 action potentials, activated at rates up
      to 100 Hz, showed modest amplitude reduction. Recordings in the apical dendrites,
      150 microns from the soma, showed smaller initial amplitudes and much greater
      decrement during trains. Higher frequencies caused a greater rate of reduction
      with a lower final amplitude. 3. Calcium concentration changes ([Ca2+]i),
      measured with the fluorescent indicator Calcium Green-1 and a fast, cooled charge
      coupled device (CCD) camera, were detected over the entire length of the apical
      dendrites in response to single antidromic action potentials, although the
      changes in distal dendrites were smaller. These changes were rapid, decaying to
      half-amplitude in < 150 ms in distal dendritic locations. 4. Trains of action
      potentials at all frequencies up to 100 Hz caused transient [Ca2+]i, increases
      for each spike at 150 microns from the soma. In the last 100 microns of the
      distal branches, only the first few spikes caused a [Ca2+]i increase for
      frequencies above approximately 40 Hz. These patterns could be matched with a
      simple model of calcium influx and removal, where later spikes in a train brought
      in less calcium than earlier spikes. 5. These results show that the action
      potential amplitude and the spatial extent of their propagation in the dendrites
      is frequency dependent.

PMID- 8989381
TI  - Dopamine modulation of two subthreshold currents produces phase shifts in
      activity of an identified motoneuron.
AB  - 1. The lateral pyloric (LP) neuron is a component of the 14-neuron pyloric
      central pattern generator in the stomatogastric ganglion of the spiny lobster,
      Panulirus interruptus. In the pyloric rhythm, this neuron fires rhythmic bursts
      of action potentials whose phasing depends on the pattern of synaptic inhibition
      from other network neurons and on the intrinsic postinhibitory rebound properties
      of the LP cell itself. Bath-applied dopamine excites the LP cell and causes its
      activity to be phase advanced in the pyloric motor pattern. At least part of this
      modulatory effect is due to dopaminergic modulation of the intrinsic rate of
      postinhibitory rebound in the LP cell. 2. The LP neuron was isolated from all
      detectable synaptic input. We measured the rate of recovery after 1-s
      hyperpolarizing current injections of varying amplitudes, quantifying the latency
      to the first spike following the hyperpolarizing prepulse and the interval
      between the first and second action potentials. Dopamine reduced both the first
      spike latency and the first interspike interval (ISI) in the isolated LP neuron.
      During the hyperpolarizating pre-steps, the LP cell showed a slow depolarizing
      sag voltage that was enhanced by dopamine. 3. We used voltage clamp to analyze
      dopamine modulation of subthreshold ionic currents whose activity is affected by
      hyperpolarizing prepulses. Dopamine modulated the transient potassium current IA
      by reducing its maximal conductance and shifting its voltage dependence for
      activation and inactivation to more depolarized voltages. This outward current is
      normally transiently activated after hyperpolarization of the LP cell, and delays
      the rate of postinhibitory rebound; by reducing IA, dopamine thus accelerates the
      rate of rebound of the LP neuron. 4. Dopamine also modulated the
      hyperpolarization-activated inward current Ih by shifting its voltage dependence
      for activation 20 mV in the depolarizing direction and accelerating its rate of
      activation. This enhanced inward current helps accelerate the rate of rebound in
      the LP cell after inhibition. 5. The relative roles of Ih and IA in determining
      the first spike latency and first ISI were explored using pharmacological
      blockers of Ih (Cs+) and IA [4-aminopyridine (4-AP)]. Blockade of Ih prolonged
      the first spike latency and first ISI, but only slightly reduced the net effect
      of dopamine. In the continued presence of Cs+, blockade of IA with 4-AP greatly
      shortened the first spike latency and first ISI. Under conditions where both Ih
      and IA were blocked, dopamine had no additional effect on the LP cell. 6. We used
      the dynamic clamp technique to further study the relative roles of IA and Ih
      modulation in dopamine's phase advance of the LP cell. We blocked the endogenous
      Ih with Cs+ and replaced it with a simulated current generated by a computer
      model of Ih. The neuron with simulated Ih gave curves relating the
      hyperpolarizing prepulse amplitude to first spike latency that were the same as
      in the untreated cell. Changing the computer parameters of the simulated Ih to
      those induced by dopamine without changing IA caused only a slight reduction in
      first spike latency, which was approximately 20% of the total reduction caused by
      dopamine in an untreated cell. Bath application of dopamine in the presence of
      Cs+ and simulated Ih (with control parameters) allowed us to determine the effect
      of altering IA but not Ih: this caused a significant reduction in first spike
      latency, but it was still only approximately 70% of the effect of dopamine in the
      untreated cell. Finally, in the continued presence of dopamine, changing the
      parameters of the simulated Ih to those observed with dopamine reduced the first
      spike latency to that seen with dopamine in the untreated cell. 7. We generated a
      mathematical model of the lobster LP neuron, based on the model of Buchholtz et
      al. for the crab LP neuron.

PMID- 8989382
TI  - Electrophysiological responses of single olfactory bulb neurons to amino acids in
      the channel catfish, Ictalurus punctatus.
AB  - 1. Responses of 89 single olfactory bulb neurons from 43 channel catfish,
      Ictalurus punctatus, to amino acid odorants were recorded in vivo simultaneously
      with the electro-olfactogram (EOG). Recording time for individual neurons ranged
      from 16 to 344 min. The averaged spontaneous frequency ranged from < 1 to 16
      action potentials/s with a mean frequency of 5.2 +/- 3.6 (SD) action
      potentials/s. 2. Histological examinations of carbocyanine dye 1,1'diocadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled olfactory bulbs
      and electrical stimulation of the olfactory tracts in a subset of experiments
      suggested that the majority of the recorded olfactory bulb neurons in this study
      were mitral cells. 3. Olfactory bulb neurons responded to amino acids with either
      an excitation or suppression of the background neural activity. Of the 337
      stimulus applications, 28% of the responses were excitatory, and 33% were
      suppressive. The approximately 1:1 ratio of excitatory to suppressive responses
      for all stimulus applications suggests that suppressive responses also play
      important roles in the coding of odorant information in the channel catfish. 4.
      Responses of single olfactory bulb neurons were highly reproducible over time (up
      to 5 h). Responses to any amino acid never changed from excitation to
      suppression, or vice versa over time. 5. Single olfactory bulb neurons responded
      with excitation or suppression to more than one amino acid previously indicated
      to bind to independent receptors. 6. Estimated threshold concentrations for
      activation of an olfactory bulb neuron ranged from 10(-7) to 10(-3) M and were
      different from neuron to neuron for a particular stimulus and from stimulus to
      stimulus for a particular neuron. Responses of single olfactory bulb neurons to a
      given amino acid did not change from excitation to suppression, or vice versa,
      across different suprathreshold concentrations.

PMID- 8989383
TI  - Electrophysiological responses of single olfactory bulb neurons to binary
      mixtures of amino acids in the channel catfish, Ictalurus punctatus.
AB  - 1. For the first time in any vertebrate, responses of single olfactory bulb
      neurons to odorant mixtures were studied quantitatively in the channel catfish,
      Ictalurus punctatus. 2. Extracellular electrophysiological responses of 61 single
      olfactory bulb neurons from 36 channel catfish to binary mixtures of amino acids
      and to their components were recorded simultaneously with the electro-olfactogram
      (EOG). Tested were a total of 297 mixture trials consisting of 18 different
      stimulus pairs formed from 8 amino acids. 3. For 42% (126 of the 297) of the
      tests, no significant change (N) from spontaneous activity occurred. Responses to
      the remaining 171 tests of binary mixtures were excitatory (E; 29%) or
      suppressive (S; 29%). No response type was associated with any specific mixture
      across the neurons sampled. 4. Mixture interactions that changed response types
      (E or S) from those observed to the individual components were rare, because 89%
      of the responses of single olfactory bulb neurons to the tested binary mixtures
      were classified similarly as the responses to at least one of the components. 5.
      Responses of single olfactory bulb neurons were generally predictable for binary
      mixtures whose component responses were classified as both E, both S, and both N.
      For binary mixtures whose component responses were classified differently (e.g.,
      one component evoked excitatory responses and the other evoked suppressive
      responses), the predictability of the response was dependent on the specific
      mixture type.

PMID- 8989384
TI  - Identification and characterization of cerebral ganglion neurons that induce
      swimming and modulate swim-related pedal ganglion neurons in Aplysia brasiliana.
AB  - 1. We have identified and characterized a family of several pairs of neurons in
      the cerebral ganglion of Aplysia brasiliana that are capable of inducing,
      maintaining, or modulating a motor program that underlies swim locomotion in this
      marine mollusk. We have operationally defined these cells as command neurons
      (CNs) for swimming. 2. The command cells occur in bilateral pairs in the cerebral
      ganglion and make direct and indirect outputs to neurons in the pedal ganglia,
      including motor neurons, a central pattern generator circuit, and modulatory
      neurons that enhance muscle contractions during swimming. Several of the CNs are
      sufficient individually to induce the swim motor program (SMP), all receive
      sensory feedback from the periphery, and several interconnect with other swim
      related CNs. 3. Tonic discharges of approximately 10 Hz in CN types 1-3 (CN1-CN3)
      are capable of eliciting the oscillatory, phasic SMP as recorded in peripheral
      nerves that innervate the swim appendages, the parapodia. CN1, CN2, and CN3 make
      monosynaptic excitatory connections onto ipsilateral, contralateral, and
      bilateral pedal swim-modulatory neurons [parapodial opener-phase (POP) cells],
      respectively; and each command cell type activates the pedal central pattern
      generator (CPG), leading to sustained phasic output of motor neurons and POP
      cells. 4. Tonic firing of CN4 causes weak activation of the SMP contralaterally.
      These neurons occur as two pairs of neurons in each cerebral hemiganglion, with
      mutual electrical and chemical synaptic interconnections. CN4 cells also excite
      CN1 and CN2 cells. Thus CN4 is classified as a higher-order swim command cell
      type. 5. Command cells classified as types 5-8 (CN5-CN8), although not capable of
      inducing the SMP individually, nonetheless have strong synaptic connections with
      pedal POP cells and/or with other command neurons. These command cells may excite
      or inhibit follower cells on the same or opposite sides of the preparation and
      modulate the swim output. 6. All the command cells tested received strong input
      from mechanical stimulation, either stretch or pinching, of either parapodium.
      Mechanosensory input from the parapodia was shown to depend on the presence of
      the pedal ganglion, but not the pleural. Sensory stimulation activated command
      cells and motor neurons, but POP cells received input from sensory stimuli only
      through the cerebral ganglion, probably via command cells. The effects of applied
      mechanosensory stimuli could be entirely mimicked by motor neuron-induced
      contractions of the parapodia.

PMID- 8989385
TI  - Effect of temperature on the normal and adapted vestibulo-ocular reflex in the
      goldfish.
AB  - 1. The vestibulo-ocular reflex, a sensorimotor process, operates in a similar
      manner for homeothermic (mammals) and poikilothermic (fish) animals. However,
      individual physiological, biochemical, and/or pharmacological thermolabile
      processes that underlie the operation of this reflex could alter the operation of
      this reflex in a poikilotherm. The object of this study was to determine what
      aspects of the vestibulo-ocular reflex are affected by temperature changes
      naturally experienced by a poikilothermic animal, the goldfish. 2. Experiments
      were conducted on the visuovestibulo-(Vis-VOR) and vestibulo-ocular reflex (VOR)
      during normal operation as well as during the acquisition (learning) and
      retention (memory) phases of adaptive gain change. These studies were carried out
      at temperatures to which goldfish had been acclimated over several weeks and
      after rapid (< 5 min) shifts from this acclimation temperature. 3. Normal
      sinusoidal Vis-VOR and VOR gains before adaptation were found to be independent
      of the acclimation temperature over a wide range. Acute temperature changes of up
      to 10 degrees C either above or below a 20 degrees C acclimation temperature (Ac
      degree C = 20 degrees C) did not significantly modify normal visual and/or
      vestibular oculomotor reflex gains. 4. Surprisingly, slight reductions in
      temperature, as small as 2.5 degrees C, noticeably reduced Vis-VOR and VOR gain
      adaptations. Both short (3 h) and intermediate (up to 48 h) term reflex
      modifications were affected. Loss of adaptation was observed 10 degrees C below
      the acclimation temperature (Ac - 10 degrees C); however, return to the original
      temperature immediately restored most (60-100%) of the previously acquired Vis
      VOR and VOR gain changes. In contrast, elevation of temperature up to 10 degrees
      C above the acclimation temperature (Ac + 10 degrees C) did not alter either
      increases or decreases in the adapted Vis-VOR or VOR gain. 5. A decrease in
      temperature reduced the magnitude of an adapted VOR gain increase and elevated
      the magnitude of an adapted gain decrease, thus returning the VOR gain back
      toward its normal control gain before adaptation. Because both increases and
      decreases in VOR gain were affected by the same temperature reduction, the cold
      effect was not a generalized reflex suppression, but inactivation of a process
      responsible for maintaining VOR adaptation. 6. During the acquisition phase, the
      time course and magnitude of adaptive VOR gain increases at temperatures acutely
      set 8-10 degrees C below the acclimation temperature were similar to those
      obtained at the acclimation temperature. Because the same temperature decrease
      inactivated retention of adapted VOR gain changes, the neuronal processes
      underlying the acquisition and the retention phases of Vis-VOR or VOR adaptation
      are suggested to differ qualitatively. 7. With the use of velocity step stimuli,
      both the adapted dynamic (< 100 ms) and sustained (> 100 ms) components of VOR
      adaptation were reduced by cooling. This effect on the dynamic component
      demonstrates an alteration in the shortest latency pathway through the vestibular
      nucleus and indicates that one thermosensitive site resides in the brain stem. 8.
      These results also show that, over a wide range of temperatures (20 +/- 10
      degrees C), the neuronal processing that is responsible for the normal operation
      of the visuovestibulo- and/or vestibulo-ocular reflex and for the retention of
      reflex adaptation functions by separate physiological processes within the same
      brain stem and cerebellar circuitry. 9. We conclude that temperature exhibits a
      unique, and unexpected, state-dependent effect on sensorimotor regulation and
      adaptation for periods up to 48 h. Temperature does not alter normal VOR or the
      acquisition phase of an adapted gain change. (ABSTRACT TRUNCATED)

PMID- 8989386
TI  - GABA receptors precede glutamate receptors in hypothalamic development;
      differential regulation by astrocytes.
AB  - 1. The developmental changes in gamma-aminobutyrate (GABA)-, glutamate-, and
      glycine-mediated currents in cultured embryonic neurons (n = 134) from rat
      hypothalamus were studied with the use of whole cell voltage-clamp recording. 2.
      GABA-evoked currents were detected in neurons cultured from 15-day embryos (E15)
      a few hours after plating. Every neuron studied from the time of plating at E15
      to 2 wk later responded to GABA (30 microM). The peak and steady-state currents
      evoked by GABA increased by four- to fivefold within 2 wk in culture. The time
      constants of the desensitization of GABA currents did not change during this
      period. The properties of the responses to GABA were not altered by different
      culture densities or substrates. 3. Glycine activated receptors that were
      pharmacologically distinct from GABA receptors on hypothalamic neurons. The
      glycine responses increased by > 50-fold within 2 wk in culture. The percentage
      of cells responding to glycine (500 microM) was 20% at 0 days in vitro (DIV), and
      increased to 100% at 6 DIV. Astrocytes increased both the amplitude of glycine
      mediated currents and the percentage of cells responding to glycine. 4. Glutamate
      mediated currents developed later than GABA-mediated currents. The percentage of
      cells responding to glutamate (500 microM) increased within the 1st wk, from 20%
      on the day of plating to 100% after 6 DIV. Both the peak currents and the steady
      state currents mediated by glutamate increased by 20-fold during the 2 wk in
      culture. Both the amplitude of the responses to glutamate and the percentage of
      cells responding to glutamate were increased by growing neurons either on an
      astrocyte substrate or in high-density cultures. 5. The currents and conductance
      changes elicited by GABA were greater than those generated by glutamate or
      glycine throughout the period examined. This difference was particularly evident
      in younger cells. After 3 days in vitro, GABA (30 microM) elicited a mean current
      of 1,648 pA, whereas glutamate (500 microM) only elicited a 266-pA current, and
      glycine (500 microM) elicited a 278-pA current from neurons growing on an
      astrocyte layer. 6. The expression of amino acid receptors was heterogeneous
      among hypothalamic neurons in younger cultures. Whereas all neurons expressed
      GABA receptors, some developing neurons did not express detectable glutamate
      receptors or glycine receptors. 7. Each of the three amino acid-evoked currents
      increased from E15 (1 DIV) to E20 (1 DIV), indicating an intrinsic development in
      the expression of the amino acid receptors in vivo. The GABA, glutamate, and
      glycine currents at E15, 10 DIV were similar to the currents at E20, 5 DIV (both
      25 days after conception), suggesting parallel developmental patterns for amino
      acid receptor expression in vitro and in vivo. 8. Together, these data suggest
      that GABA may play a major role in early development because hypothalamic neurons
      are more sensitive to GABA than to either glutamate or glycine. However,
      glutamate and glycine receptors appear more sensitive to regulation by the local
      environment than GABA receptors because culture density and the astrocyte
      substrate have greater inductive effects on glutamate and glycine receptors than
      on GABA receptors.

PMID- 8989387
TI  - Segment-specific effects of FMRFamide on membrane properties of heart
      interneurons in the leech.
AB  - 1. The effects of Phe-Met-Arg-Phe (FMRF)amide (10(-6) M) on membrane properties
      of heart interneurons in the third, fourth, and fifth segmental ganglia [HN(3),
      HN(4), and HN(5) cells, respectively] of the leech were studied using
      discontinuous current-clamp and single-electrode voltage-clamp techniques.
      FMRFamide was focally applied onto the soma of the cell under investigation. 2.
      Application of FMRFamide depolarized HN(3) and HN(4) cells by evoking an inward
      current. These responses were subject to pronounced desensitization. The inward
      currents evoked by application of FMRFamide were associated with an increase in
      membrane conductance and appeared to be voltage dependent. Currents were enhanced
      at more depolarized potentials. 3. The responsiveness of the HN(3) and HN(4)
      cells was not affected when the Ca2+ concentration in the bath saline was reduced
      from normal (1.8 mM) to 0.1 mM. The depolarizing response on application of
      FMRFamide was blocked when Co2+ was substituted for Ca2+. 4. HN(3) and HN(4)
      cells did not respond to FMRFamide application in Na(+)-free solution. Inward
      currents were largely reduced when bath saline with 30% of the normal Na+
      concentration was used. When Li+ was substituted for Na+ in the saline,
      application of FMRFamide still evoked depolarizing responses in HN(3) and HN(4)
      cells. 5. We conclude that focal application of FMRFamide onto the somata of
      HN(3) and HN(4) cells evokes a voltage-dependent inward current, carried largely
      by Na+. 6. Focal application of FMRFamide onto somata of HN(5) cells
      hyperpolarized these cells by activating a voltage-dependent outward current. 7.
      HN(5) cells were loaded with Cl- until inhibitory postsynaptic potentials carried
      by Cl- reversed. Cl(-)-loaded cells still responded with a hyperpolarization when
      FMRFamide was applied onto their somata. Therefore the outward current evoked by
      FMRFamide appears to be mediated by a K+ conductance increase. 8. Application of
      FMRFamide onto the somata of HN(5) cells enhanced outward currents that were
      evoked by depolarizing voltage steps from a holding potential of -45 mV. 9. We
      conclude that the hyperpolarizing response of HN(5) cells to focal application of
      FMRFamide onto their somata is the result of an up-regulation of a voltage
      dependent K+ current.

PMID- 8989389
TI  - Modification of mastication and respiration during swallowing in the adult human.
AB  - 1. The normal interactions between respiration, mastication, and swallowing were
      studied in seated adult humans. Respiratory movements and movements of the larynx
      were recorded with mercury-elastic strain gauges placed around the rib cage and
      neck. A rigid body containing infrared-emitting diodes (IREDs) was attached to
      the forehead, and a single IRED was applied to the chin. Jaw and head movements
      were transduced using the OPTOTRAK spatial motion analysis system. Recordings
      were made before, during, and after the mastication of pieces of carrot. 2.
      Movements of the larynx were used as a marker for swallowing. Measurements were
      made of the duration of masticatory and respiratory cycles, and the phase
      relationship between the two rhythms was determined. Deviations in masticatory
      and respiratory movements during swallowing were detected; the phases of the
      masticatory and respiratory cycles in which the deviations occurred were
      determined, and the interval between each deviation and the swallowing marker was
      calculated. 3. Three characteristic swallowing patterns were observed:
      interposed, terminal, and spontaneous. Interposed swallows occurred within a
      masticatory sequence, terminal swallows ended the sequence, and spontaneous
      swallows occurred sporadically between masticatory sequences. 4. Results revealed
      that mastication could have a profound effect on the respiratory rhythm in some
      subjects. One subject, whose data were excluded from further analyses, became
      apneic for a long period, followed by short and shallow breaths near the end of
      the masticatory sequence. In most subjects, respiratory rate increased during
      mastication and then dropped below baseline as soon as mastication ended. The end
      inspiration diameter of the rib cage tended to decrease in the preswallow period
      and increase postmastication relative to baseline. 5. There was a weak but
      significant tendency for inspiration to begin during the jaw opening phase of
      mastication, but phase coupling did not become stronger as swallowing was
      approached. 6. Deviations in respiration during swallowing occurred during the
      late expiratory phase of the breathing cycle. Swallows within a masticatory
      sequence occurred most frequently during the early opening phase of the
      masticatory cycle, and terminal swallows occurred after the end of the sequence
      with the mandible in the resting, postural position. Swallowing temporarily reset
      both the masticatory and respiratory rhythms. Most swallows prolonged the
      duration of one or two respiratory cycles, however; swallows were often
      repetitive, and in some subjects two or three swallows fell within a single
      respiratory cycle, prolonging it for several seconds. 7. A tight temporal
      relationship was observed between deviations in respiration and the swallowing
      marker: all deviations occurred before or coincident with the marker. The time of
      deviations in mastication relative to the swallowing marker depended on swallow
      type. There was no link between the start of pauses in the two rhythms,
      suggesting that the commands from the swallowing central pattern generator to the
      other two pattern generators are independent. 8. We suggest that disordered
      coordination of mastication and swallowing with respiration may cause prolonged
      apnea in susceptible individuals.

PMID- 8989388
TI  - Regulation of cyclic nucleotide-gated channels and membrane excitability in
      olfactory receptor cells by carbon monoxide.
AB  - 1. The effect of the putative neural messenger carbon monoxide (CO) and the role
      of the cGMP second-messenger system for olfactory signal generation was examined
      in isolated olfactory receptor neurons (ORNs) of the tiger salamander. 2. With
      the use of whole cell voltage-clamp recordings in combination with a series of
      ionic and pharmological tests, it is demonstrated that exogenously applied CO is
      a potent activator (K1/2 = 2.9 microM) of cyclic nucleotide-gated (CNG) channels
      previously described to mediate odor transduction. 3. Several lines of evidence
      suggest that CO mediates its effect through stimulation of a soluble guanylyl
      cyclase (sGC) leading to formation of the second-messenger cGMP. This conclusion
      is based on the findings that CO responses show an absolute requirement for
      guanosine 5'-triphosphate (GTP) in the internal solution, that no direct effect
      of CO on CNG currents in the absence of GTP is detectable, and that a blocker of
      sGC activation, LY85383 (10 microM), completely inhibits the CO response. 4. The
      dose-response curve for cGMP at CNG channels is used as a calibration to provide
      a quantitative estimate of the CO-stimulated cGMP formation. This analysis
      implies that CO is a potent activator of olfactory sGC. 5. Perforated patch
      recordings using amphotericin B demonstrate that low micromolar doses of CO
      effectively depolarize the membrane potential of ORNs through tonic activation of
      CNG channels. This effect in turn regulates excitable and adaptive properties of
      ORNs and modulates neuronal responsiveness. 6. These data argue for an important
      role of the cGMP pathway in olfactory signaling and support the idea that CO may
      function as a diffusible messenger in the olfactory system.

PMID- 8989390
TI  - Dynamics of sensory afferent synaptic transmission in aortic baroreceptor regions
      on nucleus tractus solitarius.
AB  - 1. Synaptic responses of medial nucleus tractus solitarius (mNTS) neurons to
      solitary tract (ST) activation were studied in a horizontal brain slice
      preparation of the rat medulla. Slices included sections of ST sufficiently long
      that the ST could be electrically activated several millimeters from the
      recording site of cell bodies in mNTS. 2. Three types of synaptic events were
      evoked in response to ST stimulation: simple excitatory postsynaptic potentials
      (EPSPs), simple inhibitory postsynaptic potentials (IPSPs), and complex EPSP-IPSP
      sequences. Simple EPSPs had substantially shorter latencies than IPSPs (3.39 +/-
      0.65 ms, mean +/- SE, n = 42, vs. 5.86 +/- 0.71 ms, n = 6, respectively). 3. EPSP
      amplitude increased linearly with increasing hyperpolarization, with an
      extrapolated reversal potential near 0 mV. 4. EPSPs were maximal at < 0.5 Hz of
      sustained, constant-frequency ST stimulation (n = 14). EPSP amplitude declined to
      an average of 57.5% of control at 10 Hz after 2 s of sustained stimulation. With
      1 min of sustained, 100-Hz stimulation, EPSP amplitude declined to near zero. 5.
      With stimuli intermittently delivered as 100-ms bursts every 300 ms, generally
      comparable average EPSPs were evoked during constant and burst patterns of ST
      stimulation. The amplitude of the initial EPSP in each burst was very well
      maintained even at intraburst stimulation rates of 100 Hz. 6. At resting membrane
      potentials, low constant frequencies of ST stimulation (< 5 Hz) reliably elicited
      action potentials and suppressed spontaneous spiking, but higher frequencies led
      to spike failures (> 85% at 100 Hz). Between 5 and 10 Hz, this periodic
      stimulation-suppression cycle clearly entrained action potential activity to the
      ST stimuli. Similar patterns of current pulses (5 ms) reliably evoked action
      potentials with each pulse to higher frequencies (50 Hz) without failures, and
      entrainment was similar to ST stimulation. 7. In a subset of nucleus tractus
      solitarius (NTS) neurons (3 of 9 studied), bursts of ST stimuli were as much as
      50% more effective at transmitting high frequencies (> 10 Hz) of ST stimulation
      than the equivalent constant frequencies (P < 0.0001). 8. The long-latency simple
      IPSPs with no preceding EPSPs reversed to become depolarizing at potentials more
      negative than -62.9 +/- 7.0 mV (n = 5) and were blocked by the non-N-methyl-D
      aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (n = 3). The ST
      stimulation frequency-response relation of these IPSPs was similar to that for
      the short-latency EPSP response excited by ST synapses. Thus these IPSPs appear
      to be activated polysynaptically via a glutamatergic-GABAergic sequence in
      response to ST activation. 9. The results suggest that sensory afferent synapses
      in mNTS have limited transmission of high-frequency inputs. Both synaptic
      transmission and the characteristics of the postsynaptic neuron importantly
      contribute to the action potential transmission from afferent to NTS neuron and
      beyond. This overall frequency response limitation may contribute to the
      accommodation of reflex responses from sensory afferent inputs such as arterial
      baroreceptors within their physiological discharge frequency range.

PMID- 8989391
TI  - Afferent synaptic drive of rat medial nucleus tractus solitarius neurons: dynamic
      simulation of graded vesicular mobilization, release, and non-NMDA receptor
      kinetics.
AB  - 1. We have developed a comprehensive mathematical model of an afferent synaptic
      connection to the soma of a medial nucleus tractus solitarius (mNTS) neuron.
      Model development is based on numerical fits to quantitative data recorded in our
      laboratory. This work is part of a continuing collaborative effort aimed at
      identifying and characterizing the mechanisms responsible for the non-linear
      integrative properties of this first synapse in the baroreceptor reflex. 2. The
      complete model consists of three major parts: 1) a Hodgkin-Huxley (HH)-type
      membrane model of the prejunctional sensory terminal bouton; 2) a multistage
      model describing vesicular storage, adenosine 3',5'-cyclic monophosphate (cAMP)-
      and Ca(2+)-dependent mobilization, release and recycling; and 3) a HH-type
      membrane model of the postjunctional mNTS cell that includes descriptions for a
      desensitizing non-N-methyl-D-aspartate (NMDA) ionic current that is responsible
      for the fast excitatory postsynaptic potentials (EPSPs) observed in mNTS cells.
      The membrane models for both the terminal bouton and the mNTS neuron are coupled
      to separate lumped fluid compartment models describing intracellular Ca2+ ion
      concentration dynamics. 3. Our modeling strategy is twofold. The first is to
      validate model performance by reproducing a wide variety of experimental data
      both from our laboratory and from the literature. The second is to explore the
      functional aspects of the model in order to gain a greater appreciation for the
      balance between presynaptic mechanisms (e.g., terminal membrane properties and
      vesicular dynamics) and postsynaptic mechanisms (e.g., non-NMDA receptor kinetics
      and neuronal dynamics) that underlie the afferent synaptic drive of mNTS neurons.
      4. The model accurately reproduces EPSP dynamics recorded with the use of a wide
      range of stimulus protocols. The model can also mirror the unique pattern of
      graded frequency- and use-dependent reduction in peak EPSP magnitude observed
      experimentally through 60 s of constant, suprathreshold synaptic activation. We
      demonstrate how vesicular mobilization, recycling, and receptor kinetics can
      function synergistically in establishing synaptic transfer. Furthermore, we show
      that by allowing the aggregate rate of vesicle mobilization to respond in a use
      dependent manner, it is possible to compensate for the attenuating affects of
      desensitization at elevated rates of stimulation. 5. Our simulations indicate
      that the low-frequency characteristics of this synapse are dominated by vesicular
      dynamics, whereas the high-frequency properties arise from a combination of
      Ca(2+)-dependent vesicular mobilization and the kinetics of the non-NMDA
      receptor. Desensitization can influence the peak magnitude and decay time of the
      EPSP, thereby affecting synaptic throughput. However, we demonstrate that, as the
      time course of neurotransmitter in the synaptic cleft decreases, the influence of
      desensitization should be somewhat diminished. As a result, the effective
      bandwidth of the synapse increases and becomes limited by the gating
      characteristics of the non-NMDA channel. 6. The model also includes a
      neuromodulatory aspect in that the frequency response of the synapse can be
      modulated by an adenylate cyclase-mediated regulatory mechanism. Although our
      simulations indicate the behavior of a limited number of possible neuromodulatory
      agents, the results demonstrate the pivotal role such agents could play in
      modifying synaptic transfer characteristics presynaptically. 7. Both continuous
      and burst-mode tract stimulation evoke patterns of action potentials in
      spontaneously active mNTS neurons that are mimicked very well by our model. Our
      simulations demonstrate that, as the rate of stimulation increases beyond
      approximately 20-30 Hz, the inherent low-pass frequency-response characteristics
      of the synapse limit the overall dynamic range of the mNTS neuron, causing the
      postsynaptic cell to "entrain" at frequencies within its normal operating range.

PMID- 8989392
TI  - Cutaneous responsiveness of lumbar spinal neurons in awake and halothane
      anesthetized sheep.
AB  - 1. To compare the responsiveness of lumbar spinal neurons to peripheral sensory
      stimuli under normal physiological conditions and under halothane anesthesia, we
      performed a study in sheep that were prepared chronically. This permitted
      recordings to be made in the same animals either when they were awake and free
      from recent surgery, drugs, and training and only partially restrained or when
      they were anesthetized with halothane. 2. We recorded 261 units in dorsal and
      ventral horns under conscious conditions. Of these, 19% had no detectable
      receptive field (RF) and 44% had responses dominated by proprioceptive inputs;
      these units were not investigated in detail. The remaining 96 neurons (37%) had
      clearly defined cutaneous RFs. Of these, most (72%) had wide-dynamic-range (WDR;
      convergent, multireceptive) properties, 19% were low-threshold mechanoreceptive
      (LTMR), and 9% were high-threshold mechanoreceptive (HTMR). These units with
      cutaneous RFs were investigated in greater detail. 3. The spontaneous activity
      under these awake conditions was low (< 4 spikes/s) for nearly all units in all
      three categories. The mechanical threshold of the most sensitive (central) part
      of the cutaneous RF was assessed with von Frey bristles. Thresholds were < 5 mN
      for all LTMR neurons, < 1-30 mN for WDR neurons, and > 80 mN for HTMR neurons.
      The size of the low-threshold cutaneous RFs was significantly larger for WDR
      neurons (mean 46 cm2) and HTMR neurons (45 cm2) than for LTMR neurons (24 cm2).
      The RFs were distributed all over the ipsilateral hindlimb. Large RFs were mostly
      proximal, whereas small RFs were distributed relatively evenly over the limb. 4.
      Recordings were made from a further 165 units while the animals were under
      halothane anesthesia. With 86 neurons having cutaneous peripheral RFs, the
      proportions having LTMR, HTMR, or WDR characteristics were very similar to those
      in awake animals. Under halothane the ongoing activity of WDR units was slightly
      (but significantly) less. The threshold to von Frey bristle stimulation was
      significantly higher only for WDR units, in both dorsal and ventral horns. The
      mean size of cutaneous RFs was significantly larger in all classes of units
      recorded under halothane anesthesia. For WDR units this was true for cells in
      both dorsal and ventral horns. This effect on mean values was due to a larger
      proportion of units with very large fields under anesthesia, particularly in the
      dorsal horn. 5. Comparison of the data from conscious animals with published
      results of acute experiments indicates that acute recording conditions do not
      distort the relative distribution and resting characteristics of these three
      functional categories of lumbar spinal neurons as much as might have been
      expected. 6. Halothane does not have major effects on the resting sensory
      responsiveness of spinal neurons with cutaneous RFs. The increase in RF area,
      which contrasts with most results from acute studies, is likely to be due to a
      dampening of descending inhibitory control mechanisms.

PMID- 8989393
TI  - Spontaneous activity and frequency selectivity of acoustically responsive
      vestibular afferents in the cat.
AB  - 1. Recordings were made from single afferent fibers in the inferior vestibular
      nerve. Firing rates of a substantial portion of the afferents with irregular
      background activity increased in response to moderately intense tone bursts. 2.
      Spontaneous activity from acoustically responsive vestibular afferents was
      statistically analyzed and compared with data from a more widespread sampling of
      primary afferents in the cat's vestibulocochlear nerve. Acoustically responsive
      vestibular afferents had interspike interval histograms with modes > 10 ms,
      coefficients of variation > 0.15, and skews > 0.88. On the basis of spontaneous
      activity, these afferents were easily distinguishable from cochlear afferents and
      regular vestibular afferents, but no obvious features differentiated them from
      other irregular vestibular afferents. 3. The distributions of spike intervals in
      the spontaneous activity of acoustically responsive vestibular afferents were
      fitted by Erlang probability density functions describing the second-order
      interarrival times of a Poisson process initiated after a finite delay
      (refractory period). 4. Acoustically responsive vestibular afferents had broad, V
      shaped tuning curves with best frequencies between 500 and 1,000 Hz, thresholds
      of > or = 90 dB SPL, and shapes comparable with the tuning-curve "tails" of
      cochlear afferents. In contrast to cochlear-nerve afferents, acoustically
      responsive vestibular afferents did not show a strong relationship between
      spontaneous rate and threshold. 5. We compare the acoustic frequency selectivity
      of vestibular and cochlear afferents in terms of their functional and
      evolutionary relationships. Our data and those of others indicate that
      acoustically responsive vestibular afferents are likely to provide an input to
      the acoustic activation of the sternocleidomastoid muscle in humans, and they may
      provide an input to other acoustic reflexes such as the middle-ear-muscle
      reflexes.

PMID- 8989394
TI  - Competitive interactions between supernumerary and normal sensory neurons in the
      cockroach are mediated through a change in quantal content and not quantal size.
AB  - 1. The final steps in synapse formation and stabilization involve the adjustment
      of strength of connections through competitive interactions between neurons
      contacting a common target. The mechanisms underlying this competition-driven
      adjustment of synaptic strength are not well understood. We have studied one
      aspect of this phenomenon using the cercal sensory system of first instar
      cockroach nymphs. 2. Quantal analysis of excitatory postsynaptic potentials
      (EPSPs) recorded at the synapse between the lateral filiform hair sensory neuron
      (L) and giant interneuron 3 (GI3) was carried out to determine whether the
      reduction in EPSP amplitude observed in the presence of an additional sensory
      neuron ("space invader neuron" or SIN) was due to pre- or postsynaptic changes.
      3. Mean quantal content, not quantal size, was reduced at the L-GI3 synapse in
      the presence of a SIN. Fitting binomial distributions to the EPSP amplitude
      histograms gave estimates of the number of releasable quanta or of synaptic sites
      (n) and the probability of release at these sites (p). The reduction in quantal
      content is associated with a decrease in the binomial parameter n and not p,
      suggesting that there is a decrease in the number of contacts, release sites, or
      quanta available for release, rather than a change in probability of release.

PMID- 8989395
TI  - Preferential suppression of the ON pathway by GABAC receptors in the amphibian
      retina.
AB  - 1. Electrophysiological recordings were obtained from neurons in the amphibian
      intact retina and retinal slice preparations. The effects of gamma-aminobutyric
      acid (GABA) were evaluated in the presence of bicuculline or SR95531, which block
      the GABAA receptor, and baclofen, which saturates the GABAB receptor. 2. Under
      these conditions, GABA preferentially reduced ON light responses in amacrine and
      ganglion cells, apparently through a presynaptic mechanism that reduced bipolar
      cell input. GABA also produced a small hyperpolarization in the resting membrane
      potential of ganglion cells. 3. Picrotoxin blocked these effects of GABA. The
      action of GABA was duplicated by muscimol and by trans-aminocrotonic acid. Cis
      aminocrotonic acid was neither a potent nor selective agonist. This pharmacology
      is indicative of the GABAC receptor. 4. In voltage-clamp recordings of ganglion
      cells in the slice preparation, GABA produced a large chloride conductance that
      was blocked by bicuculline or SR95531, and a smaller chloride conductance that
      was not blocked by these GABAA receptor antagonists, but was blocked by
      picrotoxin. This indicates that ganglion cells possess both GABAA and GABAC
      receptors. 5. The GABAC receptor current was relatively nondesensitized.
      Consequently, whereas the peak GABAA receptor current was more than fivefold
      larger than the GABAC receptor current, after desensitization the latter current
      was larger. Both currents reversed near the chloride equilibrium potential.

PMID- 8989396
TI  - Influence of eye position on activity in monkey superior colliculus.
AB  - 1. Most recording studies on the role of the monkey superior colliculus (SC) in
      eye movement generation have so far indicated that the code of the recruited
      population of cells is a fixed vector command representing the desired saccadic
      eye displacement vector, irrespective of the position of the eyes in the orbit.
      Experimental evidence from microstimulation, lesions, and neuroanatomy, however,
      suggests that the SC may have access to an eye position signal. 2. In this paper
      we have tested the hypothesis that SC activity is influenced by eye position, by
      recording from presaccadic burst neurons while monkeys made rapid eye movements
      in the light covering a large part of the oculomotor range. 3. In four alert
      rhesus monkeys, we obtained sufficient data from 57 SC single units. The activity
      of a substantial part of these cells (30/57) appeared to be significantly
      influenced by eye position. Although the tuning properties of these cells for
      saccade amplitude and direction remained invariant for changes in eye position,
      the peak firing rate of these units was systematically influenced by the position
      of the eyes in the head. 4. We have characterized this eye position dependence of
      a neuron's activity by a qualitative, model-independent, as well as by a
      quantitative model description (gain field), which takes into account both the
      tuning properties of the cell for eye displacement vectors and the dependence of
      eye position. 5. Although a majority of gain fields had their eye position
      sensitivity vector roughly aligned with the optimal saccade vector direction
      (colinear gain field, 17/30), a substantial part of the gain fields had their eye
      position sensitivity vectors in quite different directions, approximately
      homogeneously distributed with respect to the cell's ON direction. 6. We conclude
      that the SC has access to a signal related to the position of the eyes in the
      orbit. Several hypotheses on the possible functional role of this signal, in
      relation to the neural code of the motor map, are discussed.

PMID- 8989397
TI  - Synaptically evoked prolonged depolarizations in the developing auditory system.
AB  - 1. Although synaptic transmission is known to influence many aspects of neuronal
      development, activity rates are quite low at early ages. The present study
      describes a long-lasting postsynaptic response to brief periods of synaptic
      stimulation that may underlie such an influence. Whole-cell patch clamp
      recordings were made from the lateral superior olive (LSO) in a brain slice
      preparation from early postnatal gerbils. 2. Stimulation of the excitatory
      afferent pathway from the cochlear nucleus elicited a prolonged depolarization
      (PD) in approximately 60% of the LSO neurons tested. Low frequency stimulation (1
      Hz) was as effective as tetanic stimulation in producing PDs. These synaptically
      evoked depolarizations ranged in amplitude from 3 to 32 mV and recovered
      spontaneously after 0.5-35 min. 3. The LSO neuron input resistance declined
      during every PD episode and remained significantly lower even after the membrane
      potential had recovered. These PDs were partially reversed by 2 mM Ni(+2), but 1
      microM tetrodotoxin and 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)
      were ineffective. The metabotropic glutamate receptor agonist, trans-1
      aminocyclopentane-1,3-dicarboxylic acid (40 microM), produced depolarizations
      that outlasted the exposure period by an average of 20 min and were also
      partially repolarized by 2 mM Ni(+2). In contrast, the depolarizations produced
      by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or N-methyl-D
      aspartate decayed within a much shorter period of time. 4. To test whether in
      vivo discharge rates are, in fact, very low during development, spontaneous
      activity was recorded from neurons of the auditory midbrain in gerbils before and
      during the onset of sound-evoked responses. The average discharge rate of
      auditory neurons was quite low (X = 0.4 spikes/s), although many cells displayed
      brief periods of rapid discharge rate (X = 37 spikes/ s). Together, these results
      demonstrate a novel form of developmental plasticity elicited by low rates of
      glutamatergic transmission that may involve a metabotropic pathway and prolonged
      calcium influx.

PMID- 8989398
TI  - Arachidonic-acid-activated membrane conductances in dissociated cardiac
      parasympathetic neurons from Necturus.
AB  - 1. Characteristics of the membrane currents activated by arachidonic acid (AA) in
      dissociated mudpuppy parasympathetic neurons have been determined using the
      perforated-patch whole cell recording technique. 2. In a sodium-containing
      physiological solution with 12.5 mM potassium, AA (10-50 microM) increased total
      membrane current produced by either depolarizing or hyperpolarizing voltage steps
      delivered from a holding potential of -40 mV. Decreasing the external potassium
      concentration from 12.5 to 2.5 mM shifted the reversal potential of the AA
      induced current by 10 mV rather than the approximately 42 mV predicted for a
      highly potassium-selective channel. 3. In cells kept in sodium solution plus 12.5
      mM potassium and treated with 20 microM nordihydroguaiaretic acid (NDGA), an
      inhibitor of the lipoxygenase pathway of AA metabolism, AA activated only inward
      currents following hyperpolarizing voltage steps. In this condition, the shift in
      reversal potential of the AA-induced current was 40 mV when extracellular
      potassium concentration was changed fivefold. Consequently, in cells treated with
      NDGA, AA appeared to activate only an inwardly rectifying potassium current. 4.
      Decreasing the extracellular chloride concentration by approximately 90% did not
      alter the reversal potential of the AA-activated current when the extracellular
      sodium concentration was kept constant and the external potassium concentration
      was 2.5 mM. In the low-chloride solution, AA potentiated both inward and outward
      current amplitudes. These results suggested that AA did not activate a chloride
      current in these cells. 5. In a sodium-deficient, N-methyl-D-glucamine (NMG)
      containing solution, AA only activated currents for voltage steps to potentials
      more negative than the holding potential. In the NMG-substituted solution,
      changing the extracellular potassium concentration fivefold shifted the reversal
      potential of the AA-induced current by 40 mV. Therefore, in the NMG solution, AA
      primarily activated an inwardly rectifying potassium current. 6. Exchanging the
      control solution containing AA to an external solution containing AA and barium
      (barium blocks the inwardly rectifying potassium current) shifted the current
      voltage relationship to more positive voltages such that the extrapolated
      reversal potential was approximately 0 mV. In other experiments, using the barium
      containing solution, the reversal potential for the AA-induced current was -3.3
      +/- 2.4 (SE) mV. 7. In conclusion, the results of the present study indicate that
      at least two membrane currents are activated in the presence of AA: an inwardly
      rectifying potassium current and an NDGA-sensitive, sodium-dependent current that
      has a reversal potential more positive than the potassium equilibrium potential.
      We suggest the second current component is due to the activation of a
      nonselective cationic conductance.

PMID- 8989399
TI  - Effects of furosemide on distortion product otoacoustic emissions and on neuronal
      responses in the anteroventral cochlear nucleus.
AB  - 1. The objective of this study was to precisely evaluate the relationship between
      the threshold of neurons in the anteroventral cochlear nucleus (AVCN) and the
      properties of distortion product otoacoustic emissions (DPOAEs). Response areas
      of multiunit clusters in the AVCN and DPOAEs in the ear canal were measured
      alternately in the adult gerbil during furosemide-induced changes of the
      endocochlear potential. Stimulus frequencies of the probe tones for DPOAE
      measurement were in the range of f1 = 1.7-7.6 kHz and f2 = 2.0-9.0 kHz; the ratio
      f2:f1 was always 1.18. Stimulus amplitudes were varied in 5-dB steps from 30 to
      80 dB SPL, with either equal amplitudes (L1 = L2) or unequal, with L1 set 10 dB
      above L2. Multiunit response areas were determined from cluster responses to a
      series of 100-ms tone bursts presented with a pseudo-random sequence in frequency
      and intensity. 2. Changes in the multiunit discharge properties after 50-75 mg/kg
      furosemide injection were as follows: the best frequency (BF) threshold increased
      from initial values in the range of 20-30 dB SPL to 50-80 dB SPL at 10-20 min
      postinjection and then recovered fully by 60-90 min. The spontaneous discharge
      activity decreased to zero before any changes in the frequency threshold curve
      were observed and did not return to initial values for several hours. Likewise,
      total discharge rates of stimulus elicited responses were reduced and tended to
      stay reduced even after BF threshold had fully recovered. 3. From the DPOAE
      measurements, the changes observed in the cubic distortion tone (CDT, 2f1-f2)
      emission after furosemide injection were as follows: at high levels of the probe
      tones, changes in the emission intensities generally stayed within a 10-dB range.
      The CDT amplitudes for low stimulus levels, however, were typically reduced by up
      to 40 dB, but recovered (depending on the furosemide dosage) by approximately 60
      90 min. 4. At low to moderate stimulus levels of 40-60 dB SPL, there was a near
      perfect, minute-by-minute covariation of the ear canal CDT amplitude and the BF
      threshold measured in the AVCN. A 10-dB increase in threshold was associated with
      a 5- to 7-dB decrease in the CDT emission. 5. The optimum stimulus parameter set
      for the noninvasive estimation of cochlear performance from the CDT response was
      for stimulus amplitudes L1 = 50, L2 = 40 dB SPL. 6. This experiment demonstrates
      that CDT emissions at low stimulus levels are very good predictors of the
      thresholds of cochlear afferents, but this validity is lost for BF thresholds
      greater than approximately 60-70 dB SPL. 7. The ear canal CDT amplitude is better
      correlated with the BF threshold sensitivity of neuronal response areas in the
      AVCN than with the spontaneous discharge rate or absolute above-threshold
      discharge rates.

PMID- 8989400
TI  - Neurotransmitter regulation of the heart in the nudibranch Archidoris
      montereyensis.
AB  - 1. The heart of the nudibranch mollusc Archidoris montereyensis is uniquely
      responsive to regulation by identifiable cardiac motor neurons. The
      neurotransmitters mediating the strong excitatory and inhibitory actions of the
      neurons are unknown. 2. In this study we developed an infused, in vitro
      preparation of the Archidoris heart to determine which of several cardioactive
      transmitters described in mollusks could affect changes in the rate, amplitude,
      or tonus of cardiac contractions. Several neurotransmitters we tested increased
      the rate and amplitude of heart contractions, including serotonin (threshold < 10
      nM), dopamine (100 nM), and the neuropeptides R15 alpha 2 (3 nM), small
      cardioactive peptide B (10 nM), and FMRFamide (20 microM). Myomodulin also
      excited the heart (0.8 microM) and potentiated the cardioexcitatory action of
      serotonin at subthreshold concentrations. 3. Only acetylcholine (10 nM) inhibited
      the heart, decreasing the rate, amplitude, and tonus of contraction. Glycine and
      the peptides substance P and R15 alpha 1 had no effect on the heart. 4. Antisera
      against the active neurotransmitters labeled central neurons and nerves
      innervating the heart in a pattern consistent with their putative
      cardioregulatory functions. 5. Thus, despite the simplicity of the cardiac motor
      circuit in Archidoris, contractile activity of the heart appears to be regulated
      by several neurotransmitters, each with subtly different modes and thresholds of
      action.

PMID- 8989401
TI  - Learning of sequential movements in the monkey: process of learning and retention
      of memory.
AB  - 1. To characterize procedural learning and memory, we devised a behavioral
      paradigm that allows us to examine the process of learning of new procedures,
      repeatedly and without serious difficulties for primate subjects. We trained two
      monkeys to perform a sequential button press task. Upon pressing of a home key, 2
      of 16 (4 x 4 matrix) light-emitting diode (LED) buttons (called "set") were
      illuminated simultaneously, and the monkey had to press them in a predetermined
      order that he had to find out by trial-and-error. A total of five sets (called
      "hyperset") was presented in a fixed order for completion of a trial; an error at
      any set aborted the trial. A given hyperset was repeated as a block of experiment
      until 20 successful trials were performed. Monkeys PI and BO experienced 313 and
      92 hypersets, respectively. Most of these hypersets were experienced only once (1
      block of experiment); the others (28 hypersets for monkey PI and 14 hypersets for
      monkey BO) were chosen for extensive practice. 2. The learning, indicated as the
      decrease in the number of trials to criterion and the decrease in the performance
      time, proceeded at three levels: 1) short-term and sequence-selective learning
      that occurred by repeating a particular hyperset during a block of experiment;
      our monkeys learned, to some degree, to perform a new hyperset within a short
      period (< 5 min); 2) long-term and sequence-selective learning that took place
      for each hyperset across days; by daily practice, they further improved their
      skills for performing the particular hyperset; and 3) long-term and sequence
      unselective learning that was indicated by the improvement of performance for new
      hypersets; the monkeys were required to learn many hypersets, each just once (a
      block of trials), in which they performed gradually better with more experiences
      in the 2 x 5 task. 3. To examine whether the memory was retained for a long
      period, we had the monkey learn 12 hypersets sufficiently, then we stopped the
      training and retested them after 1 or 6 mo. After the 1-mo interruption the
      performance was significantly better than that for new hypersets. After the 6-mo
      interruption the performance was not different from new hypersets in terms of the
      number of trials but was significantly better than new hypersets in terms of the
      performance time. The results suggest that motor memory (measured by performance
      time) can be retained longer than procedural memory (measured by the number of
      trials).

PMID- 8989402
TI  - Synaptic potentials and threshold currents underlying spike production in motor
      giant axons of Aglantha digitale.
AB  - 1. Motor giant axons that excite swimming muscles in the jelly-fish Aglantha
      digitale interface with units of the inner and outer nerve rings in the margin at
      the base of the bell. External recording electrodes were used to monitor
      electrical activity at different sites within the nerve ring while events in the
      motor giant axon were recorded with intracellular micropipettes placed within 100
      microns of the synaptic area. In some experiments, 4- to 6-micron-diam patch
      pipettes were used to record in situ from ion channel clusters at different
      locations along the axon. 2. Independently propagating calcium and sodium spikes
      in the motor giant axon were found to arise from different excitatory
      postsynaptic potentials (EPSPs). Two separate inputs were identified; one EPSP
      class represented an input from the pacemaker system in the inner nerve ring,
      whereas another represented an input from the giant axon in the outer nerve ring.
      EPSPs from the two nerve rings had significantly different time courses and
      amplitudes. EPSPs from the ring giant axon reached a peak in little more than 1
      ms, whereas EPSPs from the pacemaker system reached a maximum in approximately 7
      ms. These slower EPSPs may be compound events composed of postsynaptic potentials
      from multiple synapses excited in series by the passage of the pacemaker neuron
      signal. 3. The threshold for the production of calcium spikes by the slow EPSPs
      of the pacemaker system (-51 +/- 2.2 mV, mean +/- SD; n = 5) corresponded well
      with the voltage at which a net inward "T"-type calcium current first appeared in
      recordings from axon membrane patches (-55 to -50 mV); the threshold for the
      initiation of the sodium spike by the fast EPSPs of the ring giant system (-32 +/
      1.2 mV, mean +/- SD; n = 6) corresponded well with the voltage at which a net
      inward sodium current first appeared (-35 to -30 mV). 4. Inward currents were
      rarely observed in membrane patches formed using pipettes with tips of < 1 micron
      OD. Even with 4-micron pipettes, patches of membrane were sometimes obtained with
      a channel population consisting exclusively of potassium channels; calcium and
      sodium currents were found in highly discrete areas ("hot spots"). Preliminary
      findings on the undersurface of the axon, which makes synaptic contact with the
      myoepithelium, are consistent with a similar distribution. 5. The pathway by
      which the ring giant excites the motor giant axon is not definitely known. The
      synaptic delay between the peak of the ring giant action potential (monitored
      externally) and the initial rise of the fast EPSP (1.64 +/- 0.15 ms, mean +/- SD;
      n = 21) would allow for transmission at two synapses, because single synaptic
      delays at neuromuscular junctions in Aglantha are approximately 0.7 ms at 12
      degrees C. The mean synaptic delay at the slow EPSP synapse was 0.88 +/- 0.09
      (SD) ms (n = 12). 6. The delay between the impulse in the ring giant axon and the
      subsequent excitation of the motor giant axon may permit the animal to withdraw
      its tentacles and so lower the drag that would otherwise reduce the effectiveness
      of any escape swim and might induce tentacle autotomy.

PMID- 8989403
TI  - Frequency-dependent depression of excitatory synaptic transmission is independent
      of activation of MCPG-sensitive presynaptic metabotropic glutamate receptors in
      cultured hippocampal neurons.
AB  - 1. A paired-pulse paradigm, and a high-frequency train followed by a test pulse,
      were used to investigate the possible role of presynaptic metabotropic glutamate
      receptors (mGluRs) in frequency-dependent modulation of the amplitude of
      excitatory post-synaptic currents (EPSCs). Paired whole cell patch-clamp
      recordings from monosynaptically connected hippocampal neurons maintained in very
      low-density cultures were performed, using the mGluR antagonist (RS)-alpha-methyl
      4-carboxyphenylglycine (MCPG, 500 microM) and the mGluR agonist (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD, 100 microM]. 2. Paired
      pulse depression (PPD) was observed in all the excitatory pairs recorded. The
      average PPD ratio (amplitude of the 2nd EPSC divided by the amplitude of the 1st
      EPSC) was 0.80 +/- 0.1 (SD) (n = 8). Application of the mGluR antagonist MCPG had
      no effect on the amplitude of the EPSCs and did not affect the ratio of the two
      EPSCs (PPD ratio 0.79 +/- 0.2). 3. The amplitudes of 10 successive EPSCs
      stimulated at a high frequency (20 Hz) decremented on average in both 4 mM
      extracellular Ca2+ (n = 5) and in 1 mM extracellular Ca2+ (n = 6). In all pairs
      tested, posttetanic depression (PTD) was observed (PTD ratio 0.7 +/- 0.2). Bath
      application of MCPG (500 microM) did not affect the amplitudes of the EPSCs
      during the train; MCPG also did not affect PTD. 4. The mGluR agonist (1S,3R)-ACPD
      depressed the amplitudes of the EPSCs in both the paired-pulse (1st EPSC, 35 +/-
      9%; 2nd EPSC, 36 +/- 10%) and posttetanic pulse (1 and 4 mM extracellular Ca2+)
      paradigms. The amount of depression observed, both PPD and PTD, remained
      unaffected by application of (1S,3R)-ACPD. Coapplication of the antagonist MCPG
      (500 microM) blocked the effects of (1S,3R)-ACPD (100 microM). 5. We conclude
      that frequency-dependent depression of EPSC amplitudes occurs independent of
      endogenous activation of MCPG-sensitive mGluRs in cultured hippocampal neurons.
      Moreover, we demonstrate that exogenous activation of mGluRs by the agonist
      (1S,3R)-ACPD can produce additional EPSC depression above that already present
      due to frequency-dependent mechanisms.

PMID- 8989404
TI  - Proprioceptive consequences of tendon vibration during movement.
AB  - 1. Previous studies have used tendon vibration to investigate kinesthetic
      illusions in the isometric limb and end point control in the moving limb. These
      previous studies have shown that vibration distorts the perceptions of static
      joint angle and movement and causes systematic errors in the end point of
      movement. In this paper we describe the effects of tendon vibration during
      movement while human subjects performed a proprioceptively coordinated motor
      task. In an earlier study we showed that the CNS coordinates this motor task-a
      movement sequence-with proprioceptive information related to the dynamic position
      and velocity of the limb. 2. When performing this movement sequence, each subject
      sat at a table and opened the right hand as the right elbow was passively rotated
      in the extension direction through a prescribed target angle. Vision of the arm
      was prevented, and the movement velocity was changed randomly from trial to
      trial, leaving proprioception as the only useful source of kinematic information
      with which to perform the task. 3. In randomly occurring trials, vibration was
      applied to the tendon of the biceps brachii, a muscle that lengthens during elbow
      extension. In some experiments the timing of tendon vibration was varied with
      respect to the onset of elbow rotation, and in other experiments the frequency of
      vibration was varied. In each experiment we compared the accuracy of the
      subject's response (i.e., the elbow angle at which the subject opened the hand)
      in trials with tendon vibration with the accuracy in trials without tendon
      vibration. 4. The effect of tendon vibration depended on the frequency of
      vibration. When the biceps tendon was vibrated at 20 Hz, subjects opened the hand
      after the elbow passed through the target angle ("overshooting"). Overshooting is
      consistent with an underestimate of the actual displacement or velocity of the
      elbow. Vibration at 30 Hz had little or no effect on the elbow angle at hand
      opening. Vibration at 40 Hz caused subjects to open the hand before the elbow
      reached the target angle ("undershooting"). Undershooting is consistent with an
      overestimate of the actual displacement or velocity of the elbow. The size of the
      error depended on the velocity of the passively imposed elbow rotation. 5. The
      effect of tendon vibration also depended on the timing of vibration. If 40-Hz
      vibration began at the onset of movement, the subject undershot the target. If 40
      Hz vibration started 5 s before movement onset and continued throughout the
      movement, the undershoot error increased in magnitude. However, if 40-Hz
      vibration started 5 s before movement onset and then stopped at movement onset,
      the subject overshot the target. When vibration was shut off during movement, a
      transition occurred from an over-shooting error to an undershooting error at a
      time that depended on the velocity of elbow rotation. 6. In a separate
      experiment, subjects were instructed to match either the perceived dynamic
      position or the perceived velocity of rotation imposed on the right elbow by
      actively rotating the left elbow. In both matching tasks, tendon vibration
      produced oppositely directed errors depending on the frequency of vibration.
      Vibration at 20 Hz produced a perception of decreased elbow velocity and a bias
      in dynamic position in the flexion direction, and vibration at 40 Hz produced the
      opposite perceptions. 7. We conclude that muscle spindle afferents, which are
      activated by tendon vibration, are an important source of the dynamic position
      and velocity information that the CNS uses to coordinate this movement sequence
      task. The observed effects of vibration timing and frequency suggest that
      perceptual changes evoked by vibration cannot be explained by the simple
      summation of sensory input evoked by movement and by vibration. Rather, the bias
      in perception produced by vibration appears to be related to the difference
      between vibration- and movement-evoked activity in muscle spindle afferents.

PMID- 8989405
TI  - Responses of neurons in the auditory pathway of the barn owl to partially
      correlated binaural signals.
AB  - 1. Extracellular single-unit recording in anesthetized barn owls was used to
      study neuronal response to dichotic stimuli of variable binaural correlation
      (BC). Recordings were made in the output fibers of nucleus laminaris (NL), the
      anterior division of the ventral lateral lemniscal nucleus (VLVa), the core of
      the central nucleus of the inferior colliculus (ICcC), the lateral shell of the
      central nucleus of the inferior colliculus (ICcLS), and the external nucleus of
      the inferior colliculus (ICx). 2. The response of all neurons sensitive to
      interaural time difference (ITD) varied with BC. The relationship between BC and
      impulse number fits a linear, a parabolic, or a ramp model. A linear or parabolic
      model fits most neurons in low-level nuclei. Higher order neurons in ICx did not
      respond to noise bursts with strong negative binaural correlation, creating a
      ramp-like response to BC. 3. A neuron's ability to detect ITD varied as a
      function of BC. Conversely, a neuron's response to BC changed with ITD. Neurons
      in NL, VLVa, and ICcC show almost periodic ITD response curves. In these neurons
      peaks and troughs of ITD response curves diminished as BC decreased, creating a
      flat ITD response when BC = 0. When BC was set to -1, the most favorable ITD
      became the least favorable one and vice versa. The ITD response curve of ICx
      neurons usually has a single dominant peak. The response of those neurons to a
      negatively correlated noise pair (BC = -1) showed two ITD peaks, flanking the
      position of the primary peak. 4. The parabolic BC response of NL neurons fits the
      prediction of the cross-correlation model, assuming half-wave rectification of
      the sound by the cochlea. Linear response is not predicted by the model. However,
      the parabolic and the linear neurons probably do not belong to two distinct
      groups as the difference between them is not statistically significant. Thus, the
      cross-correlation model provides a good description of the binaural response not
      only in NL but also in VLVa and ICcC. 5. Almost all ramp neurons occurred in
      either ICx or ICcLS where neurons are more broadly tuned to frequency than those
      in the lower nuclei. The synthesis of this response type requires, however, not
      only the convergence of different frequency channels but also inhibition between
      different ITD channels. We modeled the ramp response as a three-step process.
      First, different spectral channels converge to create broad frequency tuning. The
      response to variation in BC will be linear (or parabolic) because it is a sum of
      linear (parabolic) responses. Second, the activity in some adjacent ITD channels
      is subtracted by lateral inhibition. Finally, the result is rectified using a
      high threshold to avoid negative activity.

PMID- 8989406
TI  - Glycine and GABA influence binaural processing in the inferior colliculus of the
      mustache bat.
AB  - 1. The mammalian inferior colliculus contains large populations of binaural cells
      that are excited by stimulation of the contralateral ear and are inhibited by
      stimulation of the ipsilateral ear, and are called excitatory/inhibitory (EI)
      cells. Neurons with EI properties are initially created in the lateral superior
      olive (LSO), which, in turn, sends strong bilateral projections to the inferior
      colliculus. The questions that we address in this report are 1) whether the
      inhibition evoked by stimulation of the ipsilateral ear occurs at the inferior
      colliculus or whether it occurs in a lower nucleus, presumably the LSO; and 2) if
      the ipsilaterally evoked inhibition occurs at the inferior colliculus, is the
      inhibition a consequence of glycinergic innervation or is it a consequence of
      GABAergic innervation. To study these questions, we recorded from 61 EI neurons
      in the inferior colliculus of the mustache bat before and during the
      iontophoretic application of the glycine receptor antagonist, strychnine. We also
      tested the effects of the gamma-aminobutyric acid-A (GABAA) receptor antagonist,
      bicuculline, on 38 of the 61 neurons that were tested with strychnine. The main
      finding is that glycinergic or GABAergic inhibition, or both, contribute to the
      ipsilaterally evoked inhibition in approximately 50% of the EI neurons in the
      inferior colliculus. 2. Strychnine and bicuculline had different effects on the
      magnitude of the spike counts evoked by stimulation of the contralateral
      (excitatory) ear. On average, strychnine caused the maximum spike count evoked by
      contralateral stimulation to increase by only 23%. The relatively small effects
      of strychnine on response magnitude are in marked contrast to the effects of
      bicuculline, which usually caused much larger increases in spike counts. For
      example, although strychnine caused spike counts to more than double in
      approximately 25% of the collicular neurons, bicuculline caused a doubling of the
      spike count in approximately 60% of the cells. 3. The inhibitory influences of
      ipsilateral stimulation were evaluated by driving the neurons with a fixed
      intensity at the contralateral ear and then documenting the reductions in spike
      counts due to the presentation of progressively higher intensities at the
      ipsilateral ear. In 64% of the neurons sampled, blocking glycinergic inhibition
      with strychnine had little or no effect on the ipsilaterally evoked inhibition.
      These cells remained as strongly inhibited during the application of strychnine
      as they did before its application. In addition, the ipsilateral intensity that
      produced complete or nearly complete spike suppression in the predrug condition
      was also unchanged by strychnine. 4. In 36% of the neurons, strychnine markedly
      reduced the degree of ipsilaterally evoked spike suppression. In five of these
      neurons, there was a complete elimination of the ipsilateral inhibition: these
      neurons were transformed from strongly inhibited EI neurons into monaural
      neurons. 5. The influence of both strychnine and bicuculline was tested
      sequentially in 38 neurons. In about one-half of these cells, (53%, 20/38) the
      ipsilaterally evoked inhibition was unaffected by either drug. In 10 other units
      (26%), both drugs substantially reduced or eliminated the ipsilaterally evoked
      inhibition. In most of these cells, both bicuculline and strychnine reduced the
      ipsilaterally evoked inhibition to a similar degree. In the remaining eight cells
      studied with both drugs (21%), the ipsilaterally evoked inhibition was reduced or
      eliminated by one of the drugs, but not by both. 6. These results show that both
      glycinergic and GABAergic projections influence the ipsilaterally evoked
      inhibition in about one-half of the EI neurons in the inferior colliculus. The
      glycinergic inhibition elicited by ipsilateral stimulation is most likely due to
      projections from the ipsilateral lateral superior olive, whereas the GABAergic
      inhibition evoked by ipsilateral stimulation is most likely caused b

PMID- 8989407
TI  - Activity-dependent response depression in rat hippocampal CA1 pyramidal neurons
      in vitro.
AB  - 1. A gradual and prolonged decrease of the response, termed here "depression,"
      evoked by repeated activation with transmembrane current stimuli was analyzed in
      rat CA1 hippocampal pyramidal cells under single-electrode current clamp by the
      use of the in vitro slice technique. 2. Depression was induced by 2-s duration
      0.3- to 0.7-nA current pulses presented as a sequence of 12 stimuli at 3- to 60-s
      intervals. Sinusoidal currents (0.5-1.0 nA) at 5-Hz or 200-ms pulses repeated at
      0.3-0.5/s, which may be more natural stimulations, also induced depression. 3.
      Depression outlasted stimulation up to 170 s in all cells tested. The initial
      high rate spike burst changed little (< 20%), whereas the lower rate adapted
      response decreased markedly (> 40%). Thus neurons increased their rate of
      adaptation. The afterhyperpolarizations following pulse-evoked responses
      increased in duration and amplitude with depression. There were input resistance
      (Rin) reductions at depolarized membrane potentials and during pulses. However,
      Rin reductions were considerably smaller or altogether absent late during
      interpulse intervals. Sub-threshold current stimuli were ineffective, indicating
      that spike activity was necessary to elicit depression. 4. Depression was 1)
      insensitive to the toxin omega-Agatoxin-IVA (omega-Aga-IVA; 0.5 microM), which
      blocked synaptic transmission, revealing a key involvement of intrinsic
      properties and little if any synaptic participation; 2) insensitive to 4
      aminopyrydine (2.00-4.00 mM), which greatly enhanced excitatory and inhibitory
      synaptic efficacy, again suggesting little synaptic involvement and a principal
      postsynaptic participation, and no participation of the K(+)-mediated currents IA
      and ID; 3) abolished by carbamalcholine (5.0-20.0 microM)- an effect blocked by
      atropine (1.0-10.0 microM)- and reduced by Ca(2+)-free solutions, and by
      intracellular injection of the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA), suggesting that Ca(2+)-dependent K(+)
      mediated currents are key factors, with a less important participation of the
      K(+)-mediated IM current. 5. We conclude that depression was due to activity
      dependent modifications in intrinsic properties, with little if any synaptic
      participation. Depression may be functionally significant because it was induced
      by potentially natural stimulations. A model is proposed that accounts for the
      main traits of depression. In the model, depression was induced by a gradual
      decline of the speed at which Ca2+ was buffered intracellularly; an increase in
      the IK(Ca)S activation rate constant also simulated depression.

PMID- 8989408
TI  - Muscarine inhibits omega-conotoxin-sensitive calcium channels in a voltage- and
      time-dependent mode in the human neuroblastoma cell line SH-SY5Y.
AB  - 1. Calcium channel modulation by muscarine was investigated in cultured human
      neuroblastoma SH-SY5Y cells using the whole cell variant of the patch-clamp
      technique. 2. In SH-SY5Y cells, omega-conotoxin (omega-CgTx)-sensitive, high
      voltage-activated Ca2+ current density gradually increased from approximately 1
      microA/cm2 in undifferentiated cells to 4 microA/cm2 after approximately 20 days
      of application of the differentiating agent retinoic acid. 3. In differentiated
      SH-SY5Y cells, muscarine reversibly decreased high-voltage-activated omega-CgTx
      sensitive Ba2+ currents in a concentration-dependent way. Maximum inhibition
      (approximately 65%) measured at 0 mV was obtained with 30 microM muscarine and
      the IC50 was 1 microM. 4. Current inhibition obtained with 30 microM muscarine
      was suppressed by the specific M2 and M3 antagonists AFDX-116 and 4
      diphenylacetoxy-N-methyl-piperidine methiodide (0.3 microM; 87% suppression), but
      not by the M1 antagonist pirenzepine. 5. Muscarine-induced current suppression
      was prevented by pretreatment of the cells with pertussis toxin and mimicked by
      intracellular application of guanosine 5'-[gamma-thio]triphosphate. 6. In several
      cells, muscarinic inhibition was characterized by a clear slowdown of Ba2+
      current activation at low test potentials. Both inhibition and slowdown of
      activation were attenuated at more positive potentials and could be partially
      relieved by strong conditioning depolarizations. 7. These results indicate that
      muscarinic inhibition of omega-CgTx-sensitive Ca2+ channel current occurs through
      activation of specific muscarinic receptors and the modulatory mechanism operates
      through activation of a guanosine 5'-triphosphate-binding protein sensitive to
      pertussis toxin. Our results suggest that a blocking molecule interacts in a
      voltage-dependent manner with the Ca2+ channel without involvement of
      intracellular Ca2+ mobilization or activation of protein kinase C or cyclic
      nucleotide protein kinases. A simple model describing the reactions involved is
      proposed.

PMID- 8989409
TI  - Dorsal horn projection targets of ON and OFF cells in the rostral ventromedial
      medulla.
AB  - 1. The rostral ventromedial medulla (RVM) participates in the modulation of
      nociceptive transmission by spinal cord neurons. Previous anatomic studies have
      demonstrated that RVM neurons project to laminae I, II, and V of the dorsal horn;
      laminae VII and VIII of the intermediate and ventral horns; the intermediolateral
      column; and lamina X. The RVM contains at least three physiologically defined
      classes of neurons, two of which, the ON and the OFF cells, have been implicated
      in nociceptive modulation. Because these cells classes are intermingled in the
      RVM, it has not been possible to determine the spinal laminar projection targets
      of ON and OFF cells by anatomic methods. Therefore in the current study we
      employed antidromic microstimulation methods to determine the laminar projections
      of two of the three classes of RVM neurons, the ON and the OFF cells. 2. In
      lightly anesthetized (with methohexital sodium) rats, single-unit extracellular
      recordings were made from 48 RVM neurons that were physiologically characterized
      as ON (30) or OFF (18) cells. The recording locations of 45 of these neurons were
      recovered. Thirty-seven were found in the nucleus raphe magnus and eight were
      located near its dorsal and lateral borders. 3. Thirty-two physiologically
      identified RVM neurons (18 ON and 14 OFF cells) were antidromically activated
      from the cervical spinal cord using a monopolar stimulating electrode. The
      stimulating electrode was moved systematically in the white matter until
      antidromic activation could be produced with currents of < or = 20 microA (6.1 +/
      0.7 microA, mean +/- SE). The points from which minimum currents were required
      to antidromically activate the neurons were located mainly in the ipsilateral
      dorsolateral funiculus (DLF) (27 of 32). In a few cases, lowest antidromic
      threshold currents were found near the border between the DLF and ventrolateral
      funiculus (VLF) or, rarely, in the VLF itself. In these cases, the cell
      recordings were found to be near the dorsal boundary of the RVM. 4. While one
      electrode was used to stimulate the parent axon in the lateral funiculus, a
      second was used to explore the gray matter for the presence of collateral
      branches. The identification of a branch was initially determined by an increase
      in antidromic latency. At the same rostrocaudal plane of the spinal cord,
      stimulation of the DLF induced an antidromic spike that invaded the neuron
      earlier than the antidromic spike elicited by stimulation in the gray matter.
      Collateral branches were confirmed by establishing that the location of the
      minimum threshold point for antidromic activation of the neurons from the second
      electrode was in the gray matter, that the minimum current required to
      antidromically activate the neuron from that point was too low to activate the
      parent axon in the DLF, and that a collision occurred between the spikes induced
      by the two stimulating electrodes. 5. In 17 cases, physiologically identified RVM
      neurons (10 ON and 7 OFF cells) were antidromically activated from the gray
      matter of the cervical spinal cord using a current of 8.4 +/- 2.1 (SE) microA.
      Minimum threshold points for antidromic activation were found in laminae I-II (3
      ON and 4 OFF cells), lamina V (5 ON and 6 OFF cells), and regions ventral to the
      lateral reticulated area (3 ON and 2 OFF cells) of the gray matter. As indicated
      by these numbers, some neurons were antidromically activated from more than one
      gray matter region. In general, all OFF cells and 9 of 10 ON cells were
      antidromically activated from low threshold points in either laminae I-II or
      lamina V. 6. In six cases, neurons were activated from separate points located in
      two or three different laminae of the gray matter. Three OFF cells were activated
      from laminae I-II and V, one OFF cell and one ON cell were activated from lamina
      V and from more ventral points, and one ON cell was activated from laminae I-II
      and from points ventral to lamina V.

PMID- 8989410
TI  - Glutamate-gated chloride channel with glutamate-transporter-like properties in
      cone photoreceptors of the tiger salamander.
AB  - 1. Using the patch-clamp technique, we investigated whether the glutamate
      elicited current in mechanically isolated cone photoreceptors from the salamander
      retina is generated by a Cl- channel or a glutamate transporter. 2. The current
      reversed near the equilibrium potential for Cl-, was decreased by three Cl-
      channel blockers, 5-nitro-2-(3-phenyl-propylamino) benzoic acid, 4,4'
      diisothiocyanostilbene-2,2'-disulfonate, and diphenylamine 2,2'-dicarboxylic
      acid, and was eliminated when gluconate was substituted for both internal and
      external Cl-, features consistent with the current being mediated by a Cl-
      channel. 3. The single-channel conductance of the Cl- channel was estimated by
      noise analysis of the glutamate-elicited current fluctuations to be 0.7 pS with
      an open time of 2 ms. 4. The magnitude of the current was dependent on both
      internal and external Na+ and K+, features consistent with the current being
      related to the activation of a glutamate transporter. Yet changes in their
      concentrations did not affect the reversal potential of the current. 5. Taken
      together with earlier reports on this current showing that it has a glutamate
      transporter-like pharmacology, our results suggest that the glutamate-elicited
      current is carried by a Cl- channel but gated by a glutamate receptor whose
      pharmacology and ionic requirement resemble those previously described for
      glutamate transporters.

PMID- 8989411
TI  - Properties of channels mediating the apamin-insensitive afterhyperpolarization in
      vagal motoneurons.
AB  - 1. Whole cell recordings were obtained from neurons of the dorsal motor nucleus
      of the vagus in transverse slices of guinea pig medulla. From a holding potential
      of -40 mV, short depolarizing voltage steps activated two calcium-dependent
      potassium currents, Gk(Ca),1 and Gk(Ca),2. 2. Gk(Ca),1 was completely blocked by
      apamin (100 nM). Gk(Ca),2 was apamin insensitive, voltage independent, and
      reversed close to the potassium equilibrium potential. 3. Activation of Gk(Ca),2
      was associated with an increase in current variance. The channels underlying the
      slow component were analyzed by stationary and nonstationary fluctuation
      analysis. Current variance was linearly related to mean current for small current
      amplitudes but clearly deviated from linearity near the peak of Gk(Ca),2. The
      predicted single channel conductance was 6.8 +/- 2.5 (SE) pS. Probability of
      channel opening rose to at most 0.68. The average number of available Gk(Ca),2
      channels on vagal neurons was 4,437 +/- 591. 4. Power spectra were constructed
      from the peak current. Spectra were well fitted with a single Lorentzian with a
      corner frequency of 72 +/- 7 Hz. The mean burst duration of the channels was 3.8
      +/- 0.5 ms. These results indicate that a new type of calcium-activated channel
      underlies Gk(Ca),2.

PMID- 8989412
TI  - Odorant-specific spatial patterns in mucosal activity predict perceptual
      differences among odorants.
AB  - 1. Using operant techniques, rats were trained to differentially report (i.e.,
      identify) the odorants propanol, carvone, citral, propyl acetate, and
      ethylacetoacetate. After acquisition training, the animals were tested using a 5
      x 5 confusion matrix design. The results of the behavioral tests were used to
      measure the degree of perceptual dissimilarity between any pair of odorants.
      These dissimilarity measures were then subjected to multidimensional scaling
      analysis to establish a two-dimensional perceptual odor space for each rat. 2. At
      the completion of behavioral testing, the fluorescence changes in the dye di-4
      ANEPPS were monitored on the rat's nasal septum and medial surface of the
      turbinates in response to the same odorants. For each mucosal surface a 6.0 x 6.0
      mm area was sampled at 100 contiguous sites with a 10 x 10 photodiode array. 3.
      Formal statistical analysis indicated a highly significant predictive
      relationship between the relative position of an odorant's mucosal loci of
      maximal activity or "hot spot" and the relative position of the same odorant in a
      psychophysically determined perceptual odor space (F = 15.6, P < 0.001). 4. The
      results of this study suggest for the first time that odorant-induced mucosal
      activity patterns serve as the substrate for the perception of odorant quality.

PMID- 8989413
TI  - Burst responses in thalamic relay cells of the awake behaving cat.
AB  - 1. Relay cells of the dorsal lateral geniculate nucleus (LGN) respond in one of
      two modes: tonic or burst. The purpose of this study was to determine whether,
      and under what conditions, burst responses occur in LGN cells of an awake,
      behaving animal. 2. We recorded the extracellular responses of cells located in
      the A layers of LGN in two cats trained to perform a simple fixation task. In our
      paradigm, head position was fixed and gaze monitored with the use of the scleral
      search coil technique. They were trained to fixate on a small target light while
      we probed the receptive field of an isolated LGN cell with drifting gratings. 3.
      Many LGN cells (37/48; 77%) recorded in the awake cat showed some form of burst
      firing. However, the degree of burstiness a given cell displayed was relatively
      low. The probability of recording a burst response during any second within the
      fixation task was 0.09. This reflects the fact that during wakefulness, LGN cells
      are generally in a state of relative depolarization and the low-threshold Ca2+
      conductance underlying burst firing is inactivated. 4. The majority of bursts
      occurred (262/377; 71%) during visual stimulation. These comprised the initial
      response to the grating and were confined to the early phase of fixation. As the
      cat continued to hold fixation and as subsequent cycles of the grating passed
      through the cell's receptive field, the response shifted from a burst to a tonic
      firing pattern. Some bursts (67/377, 18%) were related to eye movements. All of
      these were postsaccadic, and most occurred > 150 ms from the onset of the eye
      movement. Finally, some bursts were neither visually driven nor related to eye
      movements. However, these spontaneous bursts were infrequent (41/377; 11%) and
      never rhythmic. 5. Burst firing in LGN cells has a dual purpose. During quiescent
      states such as slow-wave sleep, they support the decoupling of retinal signals
      from LGN. During the waking state, bursts can facilitate signal transmission
      during target acquisition and early phases of fixation.

PMID- 8989414
TI  - Motor adaptation to Coriolis force perturbations of reaching movements: endpoint
      but not trajectory adaptation transfers to the nonexposed arm.
AB  - 1. Reaching movements made in a rotating room generate Coriolis forces that are
      directly proportional to the cross product of the room's angular velocity and the
      arm's linear velocity. Such Coriolis forces are inertial forces not involving
      mechanical contact with the arm. 2. We measured the trajectories of arm movements
      made in darkness to a visual target that was extinguished at the onset of each
      reach. Prerotation subjects pointed with both the right and left arms in
      alternating sets of eight movements. During rotation at 10 rpm, the subjects
      reached only with the right arm. Postrotation, the subjects pointed with the left
      and right arms, starting with the left, in alternating sets of eight movements.
      3. The initial perrotary reaching movements of the right arm were highly deviated
      both in movement path and endpoint relative to the prerotation reaches of the
      right arm. With additional movements, subjects rapidly regained straight movement
      paths and accurate endpoints despite the absence of visual or tactile feedback
      about reaching accuracy. The initial postrotation reaches of the left arm
      followed straight paths to the wrong endpoint. The initial postrotation reaches
      of the right arm had paths with mirror image curvature to the initial perrotation
      reaches of the right arm but went to the correct endpoint. 4. These observations
      are inconsistent with current equilibrium point models of movement control. Such
      theories predict accurate reaches under our experimental conditions. Our
      observations further show independent implementation of movement and posture, as
      evidenced by transfer of endpoint adaptation to the nonexposed arm without
      transfer of path adaptation. Endpoint control may occur at a relatively central
      stage that represents general constraints such as gravitoinertial force
      background or egocentric direction relative to both arms, and control of path may
      occur at a more peripheral stage that represents moments of inertia and muscle
      dynamics unique to each limb. 5. Endpoint and path adaptation occur despite the
      absence both of mechanical contact cues about the perturbing force and visual or
      tactile cues about movement accuracy. These findings point to the importance of
      muscle spindle signals, monitoring of motor commands, and possibly joint and
      tendon receptors in a detailed trajectory monitoring process. Muscle spindle
      primary and secondary afferent signals may differentially influence adaptation of
      movement shape and endpoint, respectively.

PMID- 8989415
TI  - Stimulation at 1-5 Hz does not produce long-term depression or depotentiation in
      the hippocampus of the adult rat in vivo.
AB  - 1. We examined the efficacy of low-frequency trains (1-5 Hz) in producing long
      term depression (LTD) or depotentiation in the hippocampus of the awake adult rat
      and in anesthetized rats aged from 10 days to 3 mo. 2. In the dentate gyrus we
      found no evidence that low-frequency trains produce either depotentiation or LTD
      in the awake, adult animal or in the anesthetized animal at any age tested (10
      days-adult). 3. In area CA1 of both awake and anesthetized adult rats, we also
      found no evidence that low-frequency trains induced either LTD or depotentiation.
      Only in area CA1 of very young rats (10-11 days) was clear evidence for LTD and
      depotentiation obtained; at this age experiments were only possible in
      anesthetized animals. By 16 days, the ability to display both LTD and
      depotentiation was lost. 4. These experiments suggest that repetitive low
      frequency stimulation evokes a developmentally regulated form of activity
      dependent depression that in the hippocampus is limited to specific pathways in
      the young animal. Our results leave open the question of whether alternative
      patterns of activity can induce LTD and/or depotentiation in the adult awake rat.

PMID- 8989416
TI  - Neurons in the globus pallidus do not show correlated activity in the normal
      monkey, but phase-locked oscillations appear in the MPTP model of parkinsonism.
AB  - 1. To test the mode of functional connectivity in the basal ganglia circuitry, we
      studied the activity of simultaneously recorded neurons in the globus pallidus
      (GP) of a behaving rhesus monkey. The cross-correlograms of pairs of neurons in
      the GP were compared with those of neurons in the thalamus and frontal cortex and
      to the cross-correlograms of pallidal pairs after 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) treatment. 2. In contrast with cortical and thalamic
      neuronal activity, almost all pairs (n = 76/81 pairs; 93.8%, 1,629/1,651
      histograms; 98.7%) of GP neurons in the normal monkey were not driven by a common
      input. 3. The monkey was systemically treated with MPTP until the appearance of
      parkinsonian signs and an intermittent 7- to 11-Hz action/postural tremor. After
      the MPTP treatment, many pallidal neurons (49/140; 35%) became oscillatory, and
      19% (n = 31/162) of pallidal pairs had oscillatory cross-correlograms. 4. These
      results support the model of parallel processing in the basal ganglia of normal
      monkeys and suggest a breakdown of the independent activity in the parkinsonian
      state.

PMID- 8989417
TI  - Addition of carbonic anhydrase augments extracellular pH buffering in rat
      cerebral cortex.
AB  - 1. The ability of the extracellular space to buffer rapid alkaline shifts was
      studied in rat cortex in vitro and in vivo. Alkaline shifts were generated by
      iontophoresis of OH- or were evoked by pressure ejection of alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionic acid (AMPA). 2. In cortical slices, alkaline shifts
      induced by OH- were enhanced by the carbonic anhydrase (CA) inhibitor benzolamide
      (83 +/- 16%, mean +/- SE), and were decreased by superfusion of 10 mg/l CA (-59
      +/- 4%). CA had no effect at 1 mg/l, and no additional effect at 100 mg/l. 3. In
      slices, and in vivo, alkaline shifts induced by AMPA were similarly enhanced by
      benzolamide and decreased by superfusion of CA. 4. These data indicate that
      extracellular CA activity is less than that required for maximum buffering. This
      suggests that equilibrium between CO2 and bicarbonate may not be attained during
      rapid extracellular pH shifts.

PMID- 8989418
TI  - Inhibitory control of excitable dendrites in neocortex.
AB  - 1. Many dendrites of pyramidal cells in mature neocortex express active Na+ and
      Ca2+ conductances. Dendrites are also the target of numerous inhibitory synapses.
      We examined the interactions between the intrinsic excitability of dendrites and
      synaptic inhibition using whole cell recordings from the apical dendrites of
      layer 5 pyramidal cells. Experiments were performed on slices of somatosensory
      cortex from mature rats. Slices were bathed in the glutamate receptor antagonists
      2-amino-5-phosphonopentanoic acid and 6,7-dinitroquinoxaline-2,3-dione, and
      maintained at 32-36 degrees C. 2. In agreement with previous findings,
      intradendritic current injection evoked two distinct types of dendritic firing.
      Type I dendrites generated monophasic fast spikes, whereas type II dendrites
      showed more complex firing patterns, consisting of fast and slow spike
      components. 3. Stimulation of cortical layers 2/3 evoked fast inhibitory
      postsynaptic potentials (IPSPs) in all dendrites tested. IPSP reversal potentials
      were bimodally distributed, with means of about -53 and -85 mV when recorded with
      high-Cl(-)-concentration-filled electrodes. Interestingly, IPSP reversal
      potentials were correlated with the type of dendritic spiking pattern. 4. IPSPs
      were able to delay, completely block, or partially block spiking in dendrites,
      depending on the relative timing between inhibition and dendritic spiking. Slow,
      Ca(2+)-dependent spike components could be blocked selectively by IPSPs.
      Furthermore, inhibition could either phase advance or phase delay repetitive
      patterns of dendritic spiking, depending on the timing of the IPSP.

PMID- 8989419
TI  - Effect of MLF transection on the vertical vestibulocollic reflex in decerebrate
      cats.
AB  - 1. In the cat, motoneurons supplying biventer cervicis, complexus and rectus
      capitis posterior receive disynaptic input from the posterior semicircular canals
      and from the contralateral anterior canal via the medial vestibulospinal tract
      (MVST). Disynaptic excitation from the ipsilateral anterior canal reaches these
      motoneurons via the lateral vestibulospinal tract. 2. We hypothesized that if the
      MVST has a unique role in the production of the vertical vestibulocollic reflex
      (VCR) in these muscles then interruption of this tract by transection of the
      medial longitudinal fasciculus (MLF) would change the VCR responses.
      Specifically, response vector orientations would shift toward the plane of the
      ipsilateral anterior canal, and response gains would drop at high frequencies. 3.
      We lesioned the MLF bilaterally and observed no substantial effect on neck-muscle
      responses. Response vector orientations did not shift systematically toward a
      single plane, nor was there a consistent decrease in response gains at high
      frequencies. 4. As in the horizontal VCR, there is no unique contribution from
      MVST neurons; parallel pathways must play an important role in the vertical VCR.

PMID- 8989420
TI  - The immune system in vertical HIV infection: the immune response and disease
      progression.

PMID- 8989421
TI  - The value of specific pathogen-free rhesus monkey breeding colonies for AIDS
      research.

PMID- 8989423
TI  - Neutralization of primary human immunodeficiency virus type 1 isolates: a study
      of parameters implicated in neutralization in vitro.
AB  - Various studies have reported that primary human immunodeficiency viruses seem to
      be more refractory to neutralization by HIV-positive sera than T cell line
      adapted strains. In this study we also show that adaptation of the HIV-1SF-2
      strain, produced in PBMCs, to the cell line CEM-SS renders this isolate sensitive
      to neutralization by almost all the sera tested. Further neutralization studies
      should thus focus on the development of an assay involving primary isolates in
      order to detect antibodies having a neutralizing activity in vivo. Neutralization
      protocols currently use either an antibody end-point dilution assay, which
      combines a fixed inoculum of virus with serial dilutions of antibody, or an
      infectivity reduction assay, which uses serial dilutions of virus with a single
      dilution of antibody. We have developed an assay designed for studying the
      neutralization of primary isolates that combines these two approaches. Performing
      the assay on PBMCs allows all primary isolates to be analyzed, not just those
      multiplying in T cell lines. The neutralizing titer measured on PBMCs for human
      HIV-positive sera is low, but reproducible and independent of the virus titer in
      a given experiment. It can be increased about five-fold by changing the
      temperature and duration of virus-serum interaction (overnight at 4 degrees C
      instead of 1 hr at 37 degrees C). These results emphasize the need for a relevant
      neutralization assay involving primary isolates and primary cells for a better
      understanding of the role of humoral response in HIV infection.

PMID- 8989422
TI  - The neutralization relationship of HIV type 1, HIV type 2, and SIVcpz is
      reflected in the genetic diversity that distinguishes them.
AB  - Neutralizing antibody (NA) patterns in the sera of individuals naturally infected
      with human immunodeficiency virus (HIV) type 1, HIV-2, and the simian
      immunodeficiency virus (SIVcpz) to their homologous and heterologous isolates
      were determined in a peripheral blood mononuclear cell-based neutralization
      assay. We examined the role of the V3 loop of HIV-1 and SIVcpz in neutralization
      and the cross-reactivities among them. Cross-neutralization by sera of humans and
      chimpanzees naturally infected, respectively, with HIV-1 and SIVcpz isolates was
      more extensive than the infrequent and low-titer cross-neutralizations observed
      between HIV-1 and HIV-2. Neutralization of 9 of the 16 HIV-1 isolates by 9 of 10
      HIV-2 and all 3 SIVcpz antibody-positive sera were weak and sporadic (titer, 1:10
      1:160). Twelve of 15 HIV-1 sera neutralized the 2 SIVcpz isolates with titers of
      1:10-1:320 but only sporadically neutralized the 6 HIV-2 isolates (titers: 1:10
      1:20). The majority of HIV-1 and SIVcpz sera bound to the V3 peptides although
      their binding capacity did not readily reflect their neutralizing capacity. The
      HIV-2 sera did not or only weakly bound to the V3 peptides. These results suggest
      that HIV-1 and SIVcpz share some structural and functional similarities that set
      them apart from HIV-2.

PMID- 8989424
TI  - Safety and immunogenicity of UBI HIV-1MN octameric V3 peptide vaccine
      administered by subcutaneous injection.
AB  - Twenty-four HIV-seronegative men, at high risk of HIV infection, were recruited
      into a phase I/II safety and immunogenicity trial of a prototype HIV vaccine. The
      immunogen was a synthetic, monovalent, octameric HIV-1MN V3 peptide in an
      aluminum hydroxide (alum) adjuvant. The vaccine had been evaluated previously
      using a standard 0-, 1-, 6-month intramuscular schedule and was found to
      stimulate neutralizing antibody in 60-90% of volunteers. Participants were
      randomized to receive either 500 micrograms (n = 10; high dose) or 100 micrograms
      (n = 10; low dose) of immunogen or placebo (alum alone; n = 4) at 0, 1, and 6
      months by subcutaneous injection. Responses to the immunogen were evaluated by
      enzyme-linked immunosorbent assay (ELISA)-detectable antibody and by
      proliferative responses. Safety was monitored by both clinical assessment and
      regular review with a clinical psychologist. No serious adverse experiences were
      observed following administration of the assigned medication. One individual
      (placebo) seroconverted while on study, following exposure to HIV. After the
      vaccination course only four individuals (three high dose and one low dose) had
      ELISA-detectable antibody against the immunogen. In the evaluable samples, from
      19 volunteers, only 7 vaccine recipients (3 high dose and 4 low dose) had
      demonstrable lymphoproliferative responses to preparations of the immunogen.
      Subcutaneous administration of its candidate vaccine was safe but did not result
      in uniform or robust immunological responses.

PMID- 8989426
TI  - Relationship between antigenicity and immunogenicity of chimeric hepatitis B
      virus core particles carrying HIV type 1 epitopes.
AB  - We have developed a comparative study of antigenic and immunogenic properties of
      selected immunodominant HIV-1 epitopes from p24 and gp120 proteins added to C
      terminally truncated hepatitis B virus (HBV) core protein and exposed on the
      surface of chimeric core particles. Inserted p24 (121-210) and gp120/MN (306-328)
      epitopes induced the appropriate humoral and cellular immune responses against
      HIV-1. Superficially exposed region 160-192 of p24 also showed maximal B cell
      immunogenicity whereas buried region 148-162 induced maximal T cell response.
      Both recombinant proteins were also able to be recognized in vitro by T
      lymphocytes of HIV-1 asymptomatic carriers.

PMID- 8989425
TI  - Allogeneic dendritic cell induction of HIV-specific cytotoxic T lymphocyte
      responses from T cells of HIV type 1-infected and uninfected individuals.
AB  - The potential benefit of T cell-based vaccination for HIV-1 infection remains to
      be determined. Cytotoxic T lymphocytes (CTLs) appear to clear substantial
      populations of HIV-1 virus in vivo, although CTL activity may contribute to the
      decline in CD4+ T cell count observed in the course of the disease. To
      investigate further the role of specific CTL responses in the control of HIV-1
      replication, we raised primary CTL lines against a panel of conserved HIV-1
      epitopes using blood-derived dendritic cells as antigen-presenting cells (APCs).
      Specific primary human CTL responses were induced against HLA-A*0201-restricted
      peptides with dendritic cells from HIV-1-seronegative donors. This method of
      immunization elicited cytotoxic activities capable of recognizing endogenously
      processed antigen. The CTL induction protocol was extended in order to explore
      the capacity of HLA-matched allogeneic dendritic cells to evoke novel CTL
      responses in T cells from an HIV-seropositive asymptomatic individual. Allogeneic
      peptide-pulsed dendritic cells from a healthy sibling were capable of eliciting a
      CTL response directed against an HIV epitope (env814: SLLNATDIAV) that was
      initially not detected in the CTL effector population of the HIV-1-infected
      patient. The possibility of manipulating CTL specificity directed against
      multiple conserved HIV-1 epitopes represents a significant step in the evaluation
      of T cell-based vaccination for treatment of disease.

PMID- 8989427
TI  - Characterization of the expression and immunogenicity of poliovirus replicons
      that encode simian immunodeficiency virus SIVmac239 Gag or envelope SU proteins.
AB  - The effectiveness of the poliovirus vaccines to induce both systemic and mucosal
      immunity has prompted the development of this virus as a vector in which to
      express foreign proteins. Our laboratory has previously reported on the
      construction and characterization of poliovirus genomes that encode HIV-1
      proteins (Porter DC, et al.: J Virol 1996;70:2643-2649). To develop this system
      further, we have constructed poliovirus genomes, referred to as replicons, which
      encode the SIVmac239 Gag or Env SU in place of the poliovirus capsid gene (P1).
      Since the replicons do not encode capsid proteins, they are encapsidated into
      poliovirus by passage with a recombinant vaccinia virus, VVP1, which provides the
      poliovirus capsid proteins in trans. Using this system, we have derived stocks of
      the encapsidated replicons which encode the SIVmac239 or Env SU protein.
      Infection of cells with the replicon that encodes SIVmac239 Gag resulted in the
      expression of a 55-kDa protein that was released from the infected cells.
      Analysis of the sedimentation of the released proteins by sucrose density
      gradient centrifugation revealed that the protein was released from the cell in
      the form of a virus-like particle. Infection of cells with the replicons encoding
      the SIVmac239 Env SU resulted in the expression of a 63-kDa protein,
      corresponding to the molecular mass predicted for the nonglycosylated SIVmac239
      SU protein. A second protein with a molecular mass greater than 160 kDa was also
      immunoprecipitated. After enzymatic deglycosylation, this protein migrated at a
      molecular mass consistent with that for an Env SU dimer. Analysis of the medium
      from cells infected with the replicon encoding SIVmac239 Env SU revealed the
      presence of a protein of molecular mass 85-90 kDa, possibly representing a
      fragment of the SIVmac239 or Env SU protein. To determine the immunogenicity of
      the replicons encoding SIVmac239 Gag or Env SU, transgenic mice that express the
      human receptor for poliovirus, and are thus susceptible to poliovirus, were
      immunized via the intramuscular route. A serum antibody response to SIV envelope
      was detected following booster immunization, establishing that the encapsidated
      replicon was immunogenic. Finally, we demonstrate that the replicons have the
      capacity to infect peripheral blood mononuclear monocytes/macrophages, suggesting
      that this cell is a possible target for in vivo infection. The results of our
      studies, then, lend further support for the development and application of
      recombinant poliovirus replicons in a vaccine strategy.

PMID- 8989428
TI  - Multifactorial nature of noncytolytic CD8+ T cell-mediated suppression of HIV
      replication: beta-chemokine-dependent and -independent effects.
AB  - Chemokines were originally characterized by their ability to direct migration and
      induce activation of selected leukocyte populations. The beta-chemokines MIP-1
      alpha, MIP-beta, and RANTES have been implicated in the suppression of viral
      replication by CD8+ T cells from HIV-infected individuals. The present study was
      undertaken to evaluate the effect of beta-chemokines on HIV replication in
      cocultures of dendritic cells (DCs) and CD4+ T cells, and an in vitro model of
      the lymphoid microenvironment. In the acute infection system, where DCs from
      uninfected individuals are pulsed with HIV and cocultured with autologous CD4+ T
      cells, no inhibition of replication of monocytotropic or T cell tropic viral
      isolates by MIP-1 alpha, MIP-1 beta, and RANTES, alone or in combination, was
      observed. In contrast, in an endogenous infection system, where the DCs and CD4+
      T cells were obtained from HIV-infected subjects, addition of recombinant beta
      chemokines suppressed HIV replication. However, neutralizing antibodies to beta
      chemokines did not affect the suppressive activity of CD8+ T cells from HIV
      infected donors in either system, suggesting that CD8+ T cell-mediated
      suppression is not due exclusively to beta-chemokines. Furthermore, no
      significant differences in secretion of MIP-1 alpha, MIP-1 beta, and RANTES by
      purified CD8+ T cells were noted in uninfected versus HIV-infected donors,
      regardless of the stage of disease. These results indicate that HIV suppression
      by CD8+ T cells derived from HIV-infected donors is a multifactorial phenomenon
      and not limited to the action of MIP-1 alpha, MIP-1 beta, and RANTES.

PMID- 8989429
TI  - CD8+ T cell supernatants of HIV type 1-infected individuals have opposite effects
      on long terminal repeat-mediated transcription in T cells and monocytes.
AB  - CD8+ T lymphocytes of HIV-1-infected individuals can efficiently suppress HIV-1
      replication in CD4+ T lymphocytes via soluble factors. We compared the effect of
      CD8+ T cell-derived supernatants on HIV-1 LTR-driven gene expression in T cells
      and monocytic cell lines. Our results demonstrate that CD8+ T cell supernatants
      that suppressed HIV-1 LTR-driven gene expression in Jurkat T cells significantly
      enhanced expression in Tat-activated U38 monocytic cells in the presence and
      absence of mitogenic stimulation. Examination of a panel of CD8+ T cell-derived
      supernatants form HIV-infected individuals demonstrated that the extent of
      enhancement of transcription in U38 cells was mirrored in most cases by a similar
      level of suppression of transcription in Jurkat T cells. In latently infected U1
      cells treated with TNF-alpha, culture with CD8+ T cell supernatants markedly
      enhanced virus production. In addition, the percentage increase in the
      enhancement of HIV-1 LTR-driven CAT expression by CD8+ T cell supernatants
      correlated strongly (r = 0.911) with the level of p24 detected. The level of LTR
      mediated gene expression in U38 cells was not influenced by rhMIP-1 alpha rhMIP-1
      beta, or rhRANTES over a wide range of chemokine concentration. Treatment of CD8+
      T cell supernatant with a combination of antibodies to these chemokines resulted
      in a further augmentation of LTR-mediated CAT expression in U38 cells. Taken
      together, these results demonstrate that CD8+ T cell suppressive factors may have
      opposite effects on HIV-1 LTR-driven gene expression and replication dependent on
      target cell type and further suggest that the beta-chemokines do not influence
      HIV-1 LTR-mediated gene expression in monocytic cells.

PMID- 8989430
TI  - CD8+ T cells from HIV type 1-seronegative individuals suppress virus replication
      in acutely infected cells.
AB  - CD8+ lymphocytes (CD8 cells) have been shown to inhibit replication of the human
      immunodeficiency virus (HIV) in vitro when cocultured with HIV-infected CD4+
      lymphocytes (CD4 cells). This suppressive effect on HIV replication in
      experimentally infected CD4 cells has so far been demonstrated only for CD8 cells
      from HIV-seropositive individuals. In the present study we have investigated if
      CD8 cells from HIV-negative individuals can also suppress HIV replication in
      experimentally infected CD4 cells. Positively selected CD4 cells were infected
      with phenotypically different primary isolates of HIV type 1 and 2 (HIV-1 and HIV
      2). Graded numbers of CD8 cells were added to the infected cultures. The T cells
      were activated by antibodies directed against the CD3 molecule or the T cell
      receptor. Culture supernatants were harvested for HIV p24 quantitation and the
      CD8 suppression of HIV replication was calculated by comparing p24 levels from
      parallel cultures in the presence or absence of CD8 cells from different donors.
      We show that CD8 cells from unexposed HIV-seronegative blood donors are able to
      control HIV-1 and HIV-2 replication in experimentally infected autologous CD4
      cells. The antiviral activity of CD8 cells from and HIV-naive individual was
      reproducible over time and the suppressive effect was comparable to that seen
      with CD8 cells from HIV-positive individuals. The infected cells were not
      eliminated from the cultures. The suppressive effect of CD8 cells varied
      depending on the dose and biological phenotype of the virus used for infection.
      Thus, exposure to HIV in vivo is not a prerequisite for CD8 cells to exert a
      suppressive effect on HIV replication in acutely infected cells.

PMID- 8989431
TI  - The lymphocytosis-promoting agent pertussis toxin affects virus burden and
      lymphocyte distribution in the SIV-infected rhesus macaque.
AB  - Pertussis toxin from the gram-negative bacterium Bordetella pertussis is an ADP
      ribosylase that modifies Gi proteins in mammalian lymphocytes and inhibits their
      capacity to traffic from blood into lymphoid tissues. We used this compound to
      induce lymphocytosis in rhesus macaques and to study its effects on SIV
      infection. Pertussis toxin injected at 25 micrograms/kg induced a transient
      lymphocytosis that peaked 3-8 days after administration and caused a rapid,
      transient decrease in the frequency of infectious cells in blood as judged by in
      vitro virus isolation assays. Lymphocyte subsets were altered during the
      lymphocytosis interval and sustained changes in CD8+ T cell levels were noted as
      long as 53 days after pertussis toxin injection. In situ hybridization studies
      showed that pertussis toxin altered the distribution of viral RNA in lymph nodes
      during the interval of lymphocytosis, and caused long-term changes with decreased
      virus replication in some tissue specimens.

PMID- 8989432
TI  - Human plasmatic apolipoprotein H binds human immunodeficiency virus type 1 and
      type 2 proteins.
AB  - Apolipoprotein H (apo H), isolated from human plasma albumin solution, was shown
      to capture HIV-1-related antigens from antigen-positive sera (HIV-1 AG+) of AIDS
      patients, by using HIV-1-specific polyclonal antibodies. In an enzyme-linked
      immunosorbent assay and ligand blot and dot assays, apo H was able to bind
      recombinant retroviral HIV antigens, especially Gag proteins p18 of HIV-1, p26 of
      HIV-2, and Env gp160 of HIV-1. Binding was shown to be pH and NaCl dependent,
      with an optimum at acidic pH and low ionic strength. Specificity was demonstrated
      by saturation of this binding and inhibition either by homologous competition or
      by specific antisera. Binding was also observed in cell line-harvested viral
      proteins. The mechanism of this apo H-polyspecific binding is discussed in
      relation to conformational changes due to the influence of lipids or detergents.

PMID- 8989433
TI  - Failure of insulin-like growth factor type I to suppress HIV type 1 in adult or
      umbilical cord mononuclear blood cells.
AB  - Insulin-like growth factor type I (IGF-I) has been used as a treatment for
      cachexia in adults with AIDS and has been reported to show inhibitory activity
      against HIV-1IIIB in cord blood mononuclear cells (CBMCs) in vitro at low
      concentration (1%) fetal bovine serum (FCS). We evaluated the effect of IGF-I on
      MN, IIIB, and BaL strains, as well as on a patient isolate of HIV-1 in CBMCs and
      adult peripheral blood mononuclear cells (PBMCs). IGF-I failed to show any
      inhibitory effect on HIV replication in CBMCs or adult PBMCs under various
      culture conditions. In contrast to an earlier report of an antiviral effect, IGF
      I augmented HIV-1 replication in PHA-stimulated PBMCs maintained in a low
      concentration of FCS.

PMID- 8989434
TI  - Region-specific changes, gene duplications, and random deletions in the nef gene
      from HIV type 1-infected brain tissues and blood of a demented patient.

PMID- 8989454
TI  - Loss of the N-myc oncogene in a patient with a small interstitial deletion of the
      short arm of chromosome 2.
AB  - To our knowledge, only four previous cases of distal chromosome 2p deletions
      exist in the literature. We present a patient with minor facial anomalies who had
      a distal interstitial deletion of the short arm of chromosome 2,
      del(2)(p24.2p25.1). This patient had many features seen in other patients with
      distal 2p deletion including short stature, "rectangular" facies, microcephaly,
      hypotonia, and mental retardation. This patient also has sensorineural hearing
      loss which has been described in one other patient with a similar deletion. The N
      myc oncogene has been mapped to 2p24. By fluorescence in situ hybridization using
      a cDNA probe for the N-myc oncogene, this patient was found to have a deletion of
      the N-myc oncogene. This confirms the previous map location for N-myc.

PMID- 8989455
TI  - Immunodeficiency as a component of recognizable syndromes.
AB  - Immunodeficiency occurs in numerous genetic syndromes. While it is the dominant
      manifestation in primary immunodeficiencies, immune deficits may also be seen in
      a variety of other recognizable syndromes. Immunodeficiency has been reported in
      64 such conditions, adding to the 45 recognized primary immunodeficiencies. These
      uncommon syndromes with immune defects can present with: (a) growth deficiency
      (11 syndromes with disproportionate or proportionate short stature), (b) specific
      organ system dysfunction (18 with gastrointestinal, dermatologic, or neurologic
      abnormalities), (c) inborn errors of metabolism (13), (d) miscellaneous anomalies
      (10), or (e) chromosome anomalies (12). In most of the disorders, only some of
      the affected patients have immune defects. However, in 27 syndromes,
      immunodeficiency is a constant finding. We briefly review the clinical
      manifestations of each syndrome and delineate the specific associated immune
      defects. In most syndromes, the connection between the immune and other defects
      is unknown. Recognition of these conditions involving both the immune and other
      organ systems may facilitate accurate diagnosis and management as well as yield
      information regarding genes critical for the development of the involved systems.

PMID- 8989456
TI  - Laryngeal malformations in the Richieri-Costa and Pereira form of acrofacial
      dysostosis.
AB  - We report on laryngeal malformations in 5 subjects, 4 females and 1 male, with
      the autosomal-recessive Richieri-Costa and Pereira form of acrofacial dysostosis.
      Characteristics of the voice are described.

PMID- 8989457
TI  - Identification of mosaicism in Prader-Willi syndrome using fluorescent in situ
      hybridization.
AB  - We report on our findings of 4 patients with mosaicism for a deletion of
      chromosome 15, most commonly associated with Prader-Willi syndrome (PWS). We
      examined a series of typical and atypical PWS patients in order to identify
      cytogenetically undetected deletions, using fluorescence in situ hybridization.
      In 4 of the patients analyzed we detected a deletion in 14-60% of peripheral
      blood leukocytes, using four commercially available probes. Our results indicate
      that mosaicism may play a role in the etiology of some PWS cases. These findings
      may be especially useful in patients who display discrepancies between clinical
      phenotype and established diagnostic criteria. Methylation and microsatellite
      polymorphism analyses of 2 patients with low-level mosaicism failed to identify
      the deletion. We propose that fluorescence in situ hybridization is the most
      effective method for detecting somatic mosaicism, since a large number of cells
      can be individually examined for the presence or absence of a specific deletion.

PMID- 8989458
TI  - Genetics, phenotype, and natural history of autosomal dominant cyclic
      hematopoiesis.
AB  - Cyclic hematopoiesis, (CH, or cyclic neutropenia) is a rare disease manifested by
      transient severe neutropenia that recurs approximately every 21 days. The
      hematologic profile of families with the autosomal dominant form (ADCH) has not
      been well characterized, and it is unknown if the phenotype is distinct from the
      more common sporadic congenital or acquired forms of CH. We studied nine ADCH
      families whose children displayed typical CH blood patterns. Pedigrees confirmed
      dominant inheritance without evidence of heterogeneity or decreased penetrance;
      three pedigrees suggested new mutations. Families were Caucasian with exception
      of one with a Cherokee Native American founder: A wide spectrum of symptom
      severity, ranging from asymptomatic to life-threatening illness, was observed
      within families. The phenotype changed with age. Children displayed typical
      neutrophil cycles with symptoms of mucosal ulceration, lymphadenopathy, and
      infections. Adults often had fewer and milder chronic neutropenia without
      distinct cycles. While CH is commonly described as "benign", four children in
      three of the nine families died of Clostridium or E. coli colitis, documenting
      the need for urgent evaluation of abdominal pain. Misdiagnosis with other
      neutropenias was common but can be avoided by serial blood counts in index cases.
      Genetic counseling requires specific histories and complete blood counts in
      relatives at risk to assess status regardless of symptoms, especially to
      determine individuals with new mutations. We propose diagnostic criteria for ADCH
      in affected children and adults. Recombinant human granulocyte colony-stimulating
      factor treatment resulted in dramatic improvement of neutropenia and morbidity.
      The differential diagnosis from other forms of familial neutropenia is reviewed.

PMID- 8989459
TI  - Ullrich-Turner syndrome and neurofibromatosis-1.
AB  - There is a well-known association between neurofibromatosis-1 (NF1) and Noonan
      syndrome-like manifestations, including short stature, short broad neck, and
      hypertelorism. These anomalies are thought to be due to variable expression of
      the NF1 gene. We report on two girls with NF1 who were found to have the Ullrich
      Turner syndrome. Case 1, a 12-year-old white girl, was followed in a
      Neurofibromatosis Clinic because of multiple cafe-au-lait spots and a family
      history of NF1 in her mother and sister. On examination, she had short stature,
      hypertelorism, and short neck with low posterior hairline. Karyotype was 86%
      46,XY/14% 45,X. Case 2, the first child of a woman with NF1, presented at birth
      with lymphedema of hands and feet and a short broad neck. Karyotype was 45,X. At
      age 23 months she was short, had epicanthic folds, hypertelorism, narrow palate,
      right simian crease, 19 cafe-au-lait spots, and axillary freckling. We conclude
      that chromosome studies should be performed in girls with NF1 who have short
      stature and Noonan- or Ullrich-Turner-like findings. Dilemmas raised by the dual
      diagnoses of NF1 and Ullrich-Turner syndrome include potential risks of growth
      hormone therapy and estrogen replacement therapy.

PMID- 8989460
TI  - Robertsonian (15q;15q) translocation in a child with Angelman syndrome: evidence
      of uniparental disomy.
AB  - A balanced Robertsonian translocation 45,XY,t(15q15q) was detected in a patient
      with mental retardation, microcephaly, and hypertonia. Deletion of the 15q11q13
      region was unlikely based on fluorescence in situ hybridization studies that
      revealed hybridization of appropriate DNA probes to both arms of the Robertsonian
      chromosome. Inheritance of alleles from 13 highly polymorphic DNA markers on
      chromosome 15 showed paternal uniparental isodisomy. The clinical, cytogenetic,
      and molecular results are consistent with a diagnosis of Angelman syndrome.

PMID- 8989461
TI  - SPONASTRIME dysplasia: report on a female patient with severe skeletal changes.
AB  - We report on a 6-year-old girl with SPONASTRIME dysplasia, characterized by short
      limbed dwarfism, a relatively large head, midfacial hypoplasia, a saddle nose,
      moderate deformities of the vertebral bodies, striated metaphyses, and normal
      intelligence. She showed severe skeletal changes including marked delay of
      epiphyseal ossification, evident metaphyseal dysplasia, and osteopathia striata
      more pronounced than in most of the previously reported patients with this
      disorder. The patient we describe and a male patient reported by Camera et al.
      [1994: Pediatr Radiol 24:322-324] are likely to represent the severely-affected
      end of the clinical spectrum of the disorder. These finding thus rule out the X
      linked mode of inheritance of the disorder proposed by Camera et al. [1994:
      Pediatr Radiol 24: 322-324]. Alternatively, the two severely-affected patients
      may represent a variant form of the disorder. There is evidence that SPONASTRIME
      dysplasia is a genetically heterogeneous disorder.

PMID- 8989463
TI  - Congenital pulmonary lymphangiectasia and other anomalies in a child:
      provisionally unique syndrome?
AB  - Congenital pulmonary lymphangiectasis is a rare anomaly that is causally
      heterogeneous. It can occur as either an isolated finding or one manifestation of
      several multiple congenital anomaly syndromes. We describe a child with
      congenital pulmonary lymphangiectasis and the anomalies who likely has a
      provisionally unique condition.

PMID- 8989462
TI  - Syntelencephaly in an infant of a diabetic mother.
AB  - Here we report on an infant of a diabetic mother (IDM) with midline
      interhemispheric "fusion" (MIF), or syntelencephaly. This is a rare anomaly
      characterized by segmental failure of cleavage of the cerebral hemispheres and
      other brain structures in the posterior frontal and parietal regions, with a
      normal interhemispheric fissure anterior and posterior to the "fused" region.
      While there is obvious overlap with holoprosencephaly (HPE), this condition
      differs from HPE in that the midline "fusion" in MIF is complete but segmental,
      while the structural brain anomalies seen in the HPE spectrum progress smoothly
      in severity in a posterior to anterior "fusion." However, while it is apparent
      that there are key distinctions between MIF and HPE, in all likelihood they arise
      from a similar pathogenetic mechanisms. We therefore suggest that MIF is a
      distinct variant of the HPE spectrum of midline brain anomalies. Given the known
      increased incidence of HPE in IDMs, MIF is likely a maternal diabetes-associated
      malformation.

PMID- 8989464
TI  - An infant with a mosaic 45,X/46,X,psu dic(Y) (pter-->q11.2::q11.2-->pter)
      karyotype and mixed gonadal dysgenesis studied for extent of mosaicism in the
      gonads.
AB  - AN infant with mixed gonadal dysgenesis was found to have a 45,X/46,Xpsu dic(Y)
      karyotype. A low level (8%) of mosaicism for the dic(Y) cell line was observed in
      peripheral blood lymphocytes and skin fibroblasts. The dicentric nature of the Y
      chromosome became apparent in fluorescence in situ hybridization studies. The
      presence of Y centromeric sequences was demonstrated in the paraffin-embedded
      testis and streak ovary sections. The ration of Y-positive cells was higher in
      the testis than in the streak ovary.

PMID- 8989465
TI  - Autosomal dominant inheritance of Brachmann-de Lange syndrome.
AB  - A mother with mild phenotype and her severely affected son, both with classic
      manifestations of Brachmann-de Lange syndrome (BDLS), are described. This
      documented mother-to-child transmission supports the hypothesis of autosomal
      dominant transmission with intrafamilial variability. Known cases of BDLS with
      autosomal dominant inheritance are reviewed. Although most cases of BDLS are
      sporadic, a careful evaluation of parents of affected children is important for
      appropriate genetic counseling.

PMID- 8989466
TI  - Brachmann-de Lange syndrome: autosomal dominant inheritance and male-to-male
      transmission.
AB  - We report on familial occurrence of the Brachmann-de Lange syndrome (BDLS): a
      mildly affected father and his severely affected son and daughter who have
      different mothers. Both children are severely affected while the father has a
      much milder but definite BDLS phenotype. Our report documents the third example
      of male-to-male transmission and adds to the argument against exclusively
      maternal transmission in familial cases. In addition, our findings illustrate the
      occurrence of severe manifestations in cases of familial BDLS.

PMID- 8989467
TI  - Unusual complex of ventral midline anomalies: a multiple congenital
      anomalies/mental retardation syndrome.
AB  - We report on an infant boy with facial anomalies, hypoplasia of corpus callosum,
      cerebral atrophy, cleft of lower sternum, absence of palpable medial abdominal
      muscles omphalocele, hypospadias, and other anomalies. This combination of
      congenital anomalies seems not to have been described before. A clear distinction
      from other syndromes and associations with midline defects seems possible, and
      thus a specific entity may be postulated.

PMID- 8989468
TI  - Craniofacial anomalies and malformations in respiratory chain deficiency.
AB  - We report on facial anomalies including round face, high forehead, flat philtrum,
      apparently low-set ears, and short neck in 4 unrelated patients with
      mitochondrial respiratory enzyme deficiency. Pre- and postnatal growth
      retardation with microcephaly, brachydactyly, and hypoplasia of distal and middle
      phalanges was present in all 4 cases. The diagnosis of respiratory chain
      deficiency was confirmed by enzymatic and molecular studies. The combination of
      facial anomalies, prenatal growth failure, and malformations is suggestive of
      antenatal expression of the disease, and raises the question of the part that
      respiratory chain deficiencies play in human malformations.

PMID- 8989469
TI  - New form of platyspondylic lethal chondrodysplasia.
AB  - We report on a sporadic case of hitherto unknown lethal skeletal dysplasia. The
      cardinal clinical manifestations consisted of frontal bossing, cloudy corneae,
      low nasal ridge, and micrognathia, hypoplastic thorax, and rhizomelic micromelia.
      Laryngoscopy and neck CT disclosed laryngeal stenosis, and brain CT demonstrated
      hypoplasia of the corpus callosum. Skeletal survey demonstrated hypoplasia of
      facial bones and short skull base, extremely severe platyspondyly, hypoplastic
      ilia, and delayed epiphyseal ossification and rhizomelic shortness of tubular
      bones. The long bones appeared overtubulated with exaggerated metaphyseal
      flaring. The humeri were particularly short and bowed. Bowing of the radii and
      ulnae with subluxation of radial heads presented as a Madelung-like deformity.
      Unlike the long bones, the short tubular bones were not short and normally
      modeled. The skeletal changes were superficially similar to those in a group of
      lethal platyspondylic chondrodysplasias, but were inconsistent with any known
      subtypes of this group or other lethal skeletal dysplasias.

PMID- 8989470
TI  - Phenotypic discordance in a family with monozygotic twins and non-syndromic cleft
      lip and palate.

PMID- 8989471
TI  - Academicians are more likely to share each other's toothbrush than each other's
      nomenclature [Cohen, 1982].

PMID- 8989472
TI  - Transient neonatal arthrogryposis: another case.

PMID- 8989473
TI  - Holoprosencephaly in RSH/Smith-Lemli-Opitz syndrome: does abnormal cholesterol
      metabolism affect the function of Sonic Hedgehog?
AB  - The RSH/Smith-Lemli-Opitz syndrome (RSH/SLOS) is an autosomal recessive
      malformation syndrome associated with increased levels of 7-dehydro-cholesterol
      (7-DHC) and a defect of cholesterol biosynthesis at the level of 3 beta-hydroxy
      steroid-delta7-reductase (7-DHC reductase). Because rats exposed to inhibitors of
      7-DHC reductase during development have a high frequency of holoprosencephaly
      (HPE) [Roux et al., 1979], we have undertaken a search for biochemical evidence
      of RSH/SLOS and other possible defects of sterol metabolism among patients with
      various forms of HPE. We describe 4 patients, one with semilobar HPE and three
      others with less complete forms of the HPE sequence, in whom we have made a
      biochemical diagnosis of RSH/SLOS. The clinical and biochemical spectrum of these
      and other patients with RSH/SLOS suggests a role of abnormal sterol metabolism in
      the pathogenesis of their malformations. The association of HPE and RSH/SLOS is
      discussed in light of the recent discoveries that mutations in the embryonic
      patterning gene, Sonic Hedgehog (SHH), can cause HPE in humans and that the sonic
      hedgehog protein product undergoes autoproteolysis to form a cholesterol-modified
      active product. These clinical, biochemical, and molecular studies suggest that
      HPE and other malformations in SLOS may be caused by incomplete or abnormal
      modification of the sonic hedgehog protein and, possible, other patterning
      proteins of the hedgehog class, a hypothesis testable in somatic cell systems.

PMID- 8989475
TI  - The relationship between physician behaviors and blood gas values in the first
      hours of life--implications for "standards" of medical care for infants with
      respiratory distress.
AB  - It is standard practice for physicians to use blood gas (BG) evaluations when
      evaluating neonates with respiratory distress. In this study we addressed two
      questions: (1) What is the distribution of BG values in a population of infants
      receiving BG evaluation in the first 4 hours of life; and (2) How does the
      behavior of physicians correlate with BG values in these infants? We discuss the
      implications of our findings for claims about "standards" of medical care for
      newborn infants with respiratory distress. We reviewed medical records for 226
      infants with birthweight > 2000 grams who were not intubated at the time of first
      BG determination. For 199 arterial samples, mean values were pH = 7.31 +/- 0.9
      (SD); PaCO2 = 38.5 +/- 11.9 torr; PaO2 = 104 +/- 52 torr; and base excess (BE) = 
      6.5 +/- 3.8 mEq/L. These values did not differ significantly from previously
      published data for normal term infants without respiratory distress. However, the
      a/A ratio (0.45 +/- 0.19) for patients in our distressed population was
      significantly lower than reported for normal infants (0.65 +/- 0.10). For 186
      infants admitted directly to our Newborn Intensive Care Unit, the elapsed time
      from birth to BG 1 was 1.07 +/- 0.64 hours. This value did not vary significantly
      as a function of severity of illness, assessed by pH, PaCO2, PaO2, a/A ratio, or
      BE. No blood gas parameter was simultaneously sensitive and specific for
      predicting subsequent mechanical ventilation. PaCo2 1 > 80 torr was associated
      with subsequent mechanical ventilation in 4 of 4 infants; however, the positive
      predictive value of PaCO2 1 was < 50% for levels below 80 torr, and only 4 of 22
      infants eventually intubated were identified by a value of PaCO2 1 > 80 torr. The
      power of "abnormal" values of PaO2, a/A ratio, pH, or BE to predict subsequent
      intubation was even lower than PaCO2. Jurors in medical malpractice cases are
      instructed to define negligence as a deviation from the "skill and care
      ordinarily used in similar cases," and to determine the existence or absence of
      negligence guided by the testimony of "expert" witnesses. Recognizing that
      anecdotal recall of experience, even by "experts," may be inaccurate and is often
      systematically biased (the "Monday morning quarterback" phenomenon), we propose
      that the testimony of expert witnesses ought to conform, whenever possible, to a
      data-based description of medical care that actually is "ordinary used in similar
      circumstances". Our current observations suggest that (1) expert opinions of the
      "standard" to evaluate neonatal respiratory distress with a BG sample should
      reflect that the time scale is 1 to 2 hours, not 10 to 20 minutes; and (2) expert
      opinions that "abnormal" BG values either "require" or "preclude" intubation for
      most newborn infants with respiratory distress find little support in data.
      Clinical observation, not BG values, appears to be the most powerful "standard"
      by which physicians determine whether to initiate mechanical ventilation for
      newborn infants with respiratory distress.

PMID- 8989474
TI  - Association of elevated umbilical cord blood creatine kinase and myoglobin levels
      with the presence of cocaine metabolites in maternal urine.
AB  - STUDY OBJECTIVE: To determine whether an association exists between antenatal
      cocaine exposure and elevated levels of creatine kinase (CK) and myoglobin in
      umbilical cord blood collected upon delivery. STUDY POPULATION: 105 anonymous
      maternal urines with corresponding infant umbilical cords bloods. METHODS:
      Maternal urines were screened for cocaine metabolites by the Syva EMIT assay,
      with positive specimens confirmed by gas chromatography/mass spectrometry. For
      all 8 positives, plus the first 47 of the negatives collected, matched infant
      cord blood specimens were analyzed for myoglobin by radioimmunoassay and CK by
      kinetic enzyme activity assay. Cord bloods matched to the remaining 50 cocaine
      negative urines were not analyzed. A two-tailed Mann-Whitney test was used to
      evaluate the significance of differences in CK and myoglobin levels between the
      two groups. RESULTS: CK levels were evaluated twofold in the cocaine-positive
      group as compared to the cocaine negative group (mean 383 +/- 260 vs. 189 +/- 68
      IU/L, p = 0.005). Myoglobin levels were twofold higher in the cocaine-positive
      group compared to the cocaine negative group (mean 55.9 +/- 37.1 vs. 33.3 +/-
      26.8 ng/mL, p = 0.077). CONCLUSION: Antenatal cocaine exposure is associated with
      elevated cord blood CK, and possibly with elevated cord blood myoglobin.
      Additional studies, using larger study populations and more sensitive methods of
      detecting antenatal cocaine exposure, along with detailed follow-up examination
      of infants, are indicated.

PMID- 8989476
TI  - Ultrasound predictors of neonatal outcome in intrauterine growth restriction.
AB  - Our purpose was to assess the value of commonly performed ultrasound parameters
      in predicting neonatal outcome of fetuses with intrauterine growth restriction
      (IUGR). One hundred twenty-seven patients were identified on ultrasound
      examination to have IUGR. Estimated weight percentile, amniotic fluid volume,
      umbilical artery Doppler velocimetry, and head circumference/abdominal
      circumference ratio were compared with neonatal outcome. Thirty infants had
      severely adverse courses. The degree of growth restriction was strongly
      associated with adverse outcome and neonatal death. Umbilical artery Doppler
      waveforms with absent or reverse end-diastolic flow were predicted of neonatal
      death, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and
      adverse outcome in general. Oligohydramnios was predictive of adverse outcome and
      neonatal death. Logistic regression also showed that absent or reverse end
      diastolic flow and oligohydramnios were independent predictors of adverse
      outcome. Ultrasound findings of low estimated weight percentile, absent or
      reverse end-diastolic umbilical blood flow, and oligohydramnios are independent
      predictors of adverse neonatal outcome of growth restricted fetuses.

PMID- 8989477
TI  - Evaluation of hypothalamic-pituitary-adrenal axis in premature infants treated
      with dexamethasone.
AB  - Results of a national survey of the current use of steroids in newborns in 1993
      showed that 95% of the neonatologists in the United States have used
      dexamethasone for neonates at risk for chronic lung disease. Dexamethasone
      therapy for a period of a week or longer is associated with suppression of the
      hypothalamic-pituitary-adrenal axis (HPAA) in a substantial number of premature
      infants. A review of our current understanding of the biochemical tests
      evaluating HPAA function in premature infants and suggested guidelines for HPAA
      evaluation and management following dexamethasone therapy are presented.

PMID- 8989478
TI  - Decreased amniotic fluid volume at < 32 weeks of gestation is associated with
      decreased fetal movements.
AB  - The objective of this study was to assess the relationship between amniotic fluid
      volume (AFV) and fetal movements at < 32 weeks gestation as assessed by routine
      biophysical profile (BPP). From a database of 465 consecutive nonhypertensive,
      nondiabetic patients delivering at < 32 weeks gestation, patients with singleton,
      nonanomalous fetuses with AFV and fetal movements determined as part of a BPP
      assessment within 24 hours of delivery were studied. Amniotic fluid volume was
      scored 0 to 2, according to the following criteria: largest pocket in vertical
      diameter < 1 cm = 0; < 2 but > 1 cm = 1; > or = 2 cm = 2. Fetal movements (FM)
      were scored over 30 minutes: 0 if absent, 1 if 1 to 2 movements, 2 if > or = 3
      gross (limb/trunk) movements. Variables assessed included fetal presentation,
      gestational age (GA), premature rupture of membranes (PROM) as a principal
      indication for delivery, clinical chorioamnionitis (diagnosed by previously
      published criteria), histologic parameters of infection (in amnion and umbilical
      cord assessed by a single pathologist blinded to clinical data), and neonatal
      outcome. Statistical analyses included contingency tables and analysis of
      variance with p < 0.05 considered significant. Three hundred and fifty-two
      patients met the inclusion criteria. One hundred and sixty-seven patients (47%)
      had PROM as a primary indication for delivery. Infrequently, decreased fetal well
      being manifested by a BPP < 7 of 10 points was an indication for delivery despite
      prematurity (n = 7). Of the 352 patients, 80 (23%) had AFV = 0, 60 (17%) had AFV
      = 1, and 212 (60%) had AFV = 2; and 12 (3%) had FM = 0, 30 (9%) FM = 1, and 310
      (88%) FM = 2. There was a significant correlation between decreased AFV and
      decreased fetal movements (p < 0.0001). Fetal presentation and GA were not
      significantly different between patients based on score of fetal movements. The
      incidence of clinical chorioamnionitis was significantly greater in patients with
      FM = 0 (p < 0.005). We conclude that decreased AFV is associated with decreased
      fetal movements irrespective of fetal presentation or gestational age. Neonatal
      outcome (umbilical vasculitis, sepsis, intraventricular hemorrhage) is affected
      only in unusual cases in which otherwise uncompromised (nonhypoxic, nonacidotic)
      fetuses have low scores on both these antepartum ultrasonographic parameters.

PMID- 8989479
TI  - Fetal supraventricular tachycardia complicated by hydrops fetalis: a role for
      direct fetal intramuscular therapy.
AB  - Maternally administered digoxin for the treatment of fetal supraventricular
      tachycardia (SVT) complicated by hydrops fetalis may be ineffective secondary to
      poor transplacental drug transfer. We present our experience with eight
      pregnancies treated with transplacental therapy or combined maternal and direct
      fetal intramuscular therapy. Response to treatment following maternal intravenous
      administration (MIV) of digoxin or a combination of fetal intramuscular (FIM)
      digoxin and MIV is described for eight hydropic fetuses during nine successful
      pharmacologic conversions. The MIV digoxin was administered using standard
      loading and maintenance protocols. FIM was administered at a dose of 88
      micrograms/kg q 12-24 hours, to a maximum of three injections in the fetal
      buttock. Time to onset of the first two hours of sinus rhythm (TO2 degrees), time
      to onset > 90% sinus rhythm (TO > 90%), and time to resolution of hydrops fetalis
      (HF) were noted. The mean heart rate was 257 +/- 36 beats/minute and the mean
      gestational age was 29 +/- 4.8 weeks. Fetal SVT was due to a reentrant mechanism
      in all cases. For the three fetuses that underwent successful cardioversion
      following MIV digoxin (all required additional maternal antiarrhythmic drugs),
      TO2 degrees was 145 +/- 114 hours, TO > 90% was 176 +/- 55 hours, and HF resolved
      in 41 +/- 37 days. Initial combined FIM and MIV therapy in four fetuses resulted
      in a TO2 degrees of 5.5 +/- 4 hours, TO > 90% of 22 +/- 14 hours, and resolution
      of HF in 25 +/- 21 days. For the two failed cardioversions with transplacental
      treatment alone (one fetus had recurrent SVT with hydrops after initial
      successful cardioversion with MIV), TO2 degrees was 203 +/- 180 hours and TO >
      90% was 313 +/- 270 hours. Once FIM was begun in these fetuses, TO2 degrees was
      17 +/- 7 hours and TO > 90% was 60 +/- 13 hours; HF resolved in 45 days in one
      fetus, whereas the other fetus never had resolution of hydrops despite 100 days
      of antiarrhythmic therapy. Direct fetal intramuscular injection of digoxin
      combined with transplacental therapy appears to shorten the time to initial
      conversion of SVT and to sustain sinus rhythm in the fetus with SVT complicated
      by hydrops fetalis.

PMID- 8989480
TI  - Intrapartum chemoprophylaxis for group B streptococcus infection to prevent
      neonatal disease: who should be treated?
AB  - The purpose of this study was to examine the maternal risk factors associated
      with early onset Group B streptococcus (GBS) sepsis and determine the potential
      impact of intrapartum chemoprophylaxis using these risk factors. Using a
      computerized perinatal database, 26,525 deliveries over a five-year period (1989
      to 1994) were identified. Neonates with GBS-positive cultures were identified and
      the neonatal and maternal chart of each case was reviewed. Twenty-six neonates (1
      of 1000) had GBS sepsis documented by blood or cerebrospinal fluid culture.
      Maternal risk factor(s) were identified in 13 (50%) cases: preterm labor (5),
      preterm premature rupture of the membranes (5), prolonged rupture of membranes
      (6), sibling affected by symptomatic GBS infection (2), or maternal fever during
      labor (5). There were four mothers whose neonates had GBS sepsis in spite of
      intrapartum antibiotics. Intrapartum chemoprophylaxis for GBS based on risk
      factors alone will identify only half of the neonates who develop disease.
      Extension of intrapartum chemoprophylaxis to patients with risk factors appears
      to be necessary to prevent early onset disease in the other half. Since 85.7% of
      our total obstetrical population has no risk factors, this policy would require
      treating 1749 women to prevent one case of GBS sepsis. Chemoprophylaxis could be
      more appropriately targeted if mothers colonized with GBS could be identified in
      early labor.

PMID- 8989481
TI  - Hyperreactio luteinalis complicating a normal singleton pregnancy.
AB  - Hyperreactio luteinalis is a rare, usually self-limited syndrome with bilaterally
      enlarged ovaries containing multiple theca lutein cysts. It is usually associated
      with gestational trophoblastic disease and/or pregnancies that have elevated
      maternal serum hCG levels. Hyperreactio luteinalis with maternal anasarca was
      diagnosed at 19 weeks in a spontaneously conceived gestation, in a 16-year-old
      primigravida. A second trimester termination for maternal respiratory
      decompensation secondary to pleural effusions and ascites was required. There was
      no evidence of trophoblastic disease on pathological examination of the products
      of conception. Hyperreactio luteinalis may be diagnosed prenatally by ultrasound,
      and intervention may be necessary for maternal indications. Following termination
      of pregnancy, spontaneous resolution and regression of ovarian size may be
      expected.

PMID- 8989482
TI  - Prenatal diagnosis of asphyxiating thoracic dysplasia (Jeune syndrome).
AB  - Asphyxiating thoracic dysplasia (ATD), or Jeune syndrome, is an uncommon
      autosomal recessive skeletal disorder characterized by a small thorax, varying
      degrees of rhizomelic brachymelia, polydactyly, pelvic abnormalities, and renal
      anomalies. We describe prenatal sonographic examinations in the third trimester
      of a fetus with abnormal small thorax, short limbs, polyhydramnios, and absence
      of fetal respiratory movements. At 36 weeks gestation, the fetal biparietal
      diameter was 93 mm, compatible with 37 weeks; the long-bone lengths measured <
      5th percentile; the thoracic circumference (TC) measured 230 mm (< 5th
      percentile); the abdominal circumference (AC) measured 286 mm (25th percentile),
      and the TC/AC ratio was 0.80 (lower limit of normal). Our case shows that,
      although a discrepancy between gestational age and TC is prominent, TC/AC ratio
      may reach lower limit of normal in cases of fetal ATD, when fetal growth is
      compromised.

PMID- 8989483
TI  - Prenatal ultrasound diagnosis of seizures.
AB  - We present a case of fetal diagnosed by ultrasound. Clinical aspects of this
      patient and the differential diagnosis of early neonatal seizures are discussed.
      A diagnosis of fetal seizures confirmed by ultrasonography is a rare event.
      Review of the literature shows only four cases of documented fetal seizures. This
      report describes a case of fetal seizures diagnosed in utero, its management, and
      the neonatal outcome. We also discuss the differential diagnosis.

PMID- 8989484
TI  - Aneurysm of the vein of Galen: prenatal diagnosis and perinatal management.
AB  - An aneurysm of the vein of Galen is a rare arteriovenous malformation of the
      central nervous system. Fetal manifestations have included nonimmune hydrops,
      hydrocephalus, and intracranial hemorrhage. This anomaly may be diagnosed
      prenatally by several imaging modalities. A cystic cranial mass was identified by
      ultrasound in a fetus at 30 weeks gestation. Both pulsed-wave Doppler and color
      velocity imaging studies suggested aneurysm of the vein of Galen was the most
      likely diagnosis. The fetus demonstrated no evidence of hydrops on serial
      ultrasound examinations. A 2430 g female infant was delivered vaginally at 35
      weeks gestation. Postnatal management included transarterial embolization of the
      vessels feeding the aneurysm with craniectomy, an intra-aneurysmal balloon, and
      vascular microcoils. Hydrocephalus developed and a ventriculo-peritoneal shunt
      was placed. The infant has grown appropriately in the first year of life. An
      aneurysm of the vein of Galen may be diagnosed prenatally by real-time
      ultrasound, pulsed-wave Doppler, color-velocity imaging, or magnetic resonance
      imaging. The presence of this malformation should prompt close follow-up for the
      remainder of the pregnancy. Careful obstetric management and early postnatal
      intervention may lead to a favorable outcome.

PMID- 8989485
TI  - The effects of fetal blood sampling on ventricular filling patterns: differences
      between normally grown and growth-retarded fetuses.
AB  - The objective of this study was to evaluate the effect of fetal blood sampling on
      atrioventricular blood flow velocity waveforms. Flow velocity waveforms were
      measured from mitral and tricuspid valve immediately before and after fetal blood
      sampling in 25 normally grown and 10 growth-retarded fetuses. This latter group
      was characterized by abnormal Doppler indices in umbilical artery and middle
      cerebral artery suggestive of uteroplacental insufficiency as the causative
      factor of the impaired growth. The flow velocity parameters studied were peak
      velocity during early and active ventricular filling, time velocity integral, and
      fetal heart rate. Different indices were then calculated as expressions of
      ventricular diastolic function and cardiac output. In normally grown fetuses,
      both peak velocity during early diastole and time velocity integral values
      significantly increased after fetal blood sampling from both atrioventricular
      valves, whereas no significant changes were evidenced in the other parameters
      considered. Gestational age at the time of the procedure was positively related
      to the amplitude of these changes. In growth-retarded fetuses, fetal blood
      sampling induced a significant decrease in time velocity integral value form
      tricuspid valve, suggestive of a fall in right ventricle output. The amplitude of
      the decrease was significantly related to the severity of acidosis in umbilical
      vein. In conclusion, the cardiac hemodynamic response to fetal blood sampling
      differs between normally grown and growth-retarded fetuses. This difference may
      explain the higher rate of complications occurring in the latter group of fetuses
      after blood sampling.

PMID- 8989486
TI  - Maternal syphilis: the next pregnancy.
AB  - We sought to determine: (1) the perinatal outcomes in the subsequent pregnancy;
      (2) the natural history of serologic titers over the course of the two
      pregnancies; and (3) the incidence and risk factors for delivering an infant with
      congenital syphilis in the subsequent pregnancy. Over a five-year period, we
      reviewed the charts of 46 women with maternal syphilis during pregnancy who had a
      subsequent pregnancy and delivered in our institution. The initial and subsequent
      pregnancy outcomes were contrasted. To characterize the subsequent pregnancy risk
      of congenital syphilis, those women with recurrent congenital syphilis were
      contrasted to women who delivered infants without congenital syphilis. Rapid
      plasma reagin (RPR) titers in the initial and subsequent pregnancy were analyzed
      by neonatal outcome. Forty percent of the women who delivered an infant with
      congenital syphilis in their first pregnancy delivered yet another infant with
      congenital syphilis in the subsequent pregnancy. Continued cocaine use was the
      single most important risk factor for delivering another infant with congenital
      syphilis (p < 0.0001). Forty-two percent of the women who delivered an infant
      without congenital syphilis in the initial pregnancy delivered an infant with
      congenital syphilis in the subsequent pregnancy. Birthweight, the number of
      neonatal hospital days, and the incidence of respiratory distress syndrome (RDS),
      neonatal pneumonia, abruption, and positive meconium drug screens were not
      significantly different between the initial and subsequent pregnancies. As with
      the initial pregnancy, women continued to experience poor pregnancy outcomes in
      the subsequent pregnancy.

PMID- 8989487
TI  - Uterine tube more appropriate term for mammals.

PMID- 8989488
TI  - Characterization of anatomic communications among the antebrachiocarpal, middle
      carpal, and carpometacarpal joints in cattle, using intra-articular latex,
      positive-contrast arthrography, and fluoroscopy.
AB  - OBJECTIVE: To evaluate the frequency and sites of communication among the
      antebrachiocarpal, middle carpal, and carpometacarpal joints in cattle. ANIMALS:
      137 limbs were obtained from 72 fresh bovine cadavers submitted for necropsy
      because of problems unrelated to the carpus. PROCEDURE: 1 of the 3 injection
      sites was randomly assigned to both carpi of each ox, and a mixture of latex and
      barium sulfate was injected into the joint. Communication between 2 or more
      joints was determined by the presence of latex and contrast material in a joint
      adjacent to the injected joint by examination of frozen sections, positive
      contrast arthrography, and fluoroscopy. RESULTS: Communication existed among the
      3 joints in 18 specimens (13.1%). The middle carpal joint and the carpometacarpal
      joint always communicated. The antebrachiocarpal joint communicated with the
      middle carpal joint between the ulnar and intermediate carpal bones. The middle
      carpal and carpometacarpal joints always communicated between the fourth and
      fused second and third carpal bones. In a few specimens, additional sites of
      communication were identified at the palmar aspect of the fourth carpal bone and
      the fused second and third carpal bones. CONCLUSIONS AND CLINICAL RELEVANCE:
      Individual anatomic variation of the carpus in cattle should be considered when
      diagnostic or treatment protocols are established.

PMID- 8989489
TI  - Deficiencies of myocardial troponin-T and creatine kinase MB isoenzyme in dogs
      with idiopathic dilated cardiomyopathy.
AB  - OBJECTIVE: To test the hypothesis that the derangement of myocardial energy
      homeostasis characteristic of idiopathic dilated cardiomyopathy (IDCM) of
      Doberman Pinschers was attributable to deficiency of creatine kinase (CK)
      isoenzyme MB relative to CK isoenzyme MM and troponin-T (Tn-T). ANIMALS: 9
      Doberman Pinschers with advanced congestive heart failure attributable to IDCM
      and 9 mixed-breed dogs without cardiac disease (controls). PROCEDURE: Myocardial
      myofibrillar CK-MM, mitochondrial CK, and cytosolic CK-MB activities were
      determined in comparison with the concentration of cardiac-specific, myofibrillar
      protein Tn-T. Myocardial biopsy specimens were obtained after euthanasia and were
      ultrafrozen. Isoenzymes of CK were separated electrophoretically, and their
      activity was determined, using a coupled-enzyme, kinetic, fluorescent assay and
      densitometry. Troponin-T content was determined by immunoassay. RESULTS:
      Myofibrillar CK-MM and mitochondrial CK activities and Tn-T content were 25%
      lower in the dogs with IDCM than in controls, whereas cytosolic CK-MB activity
      was 50% lower. CONCLUSION: Deficiency of CK-MB activity is a component of and may
      have a central role in the energy deficiency characteristic of failing myocardium
      in IDCM of Doberman Pinschers. A side-product of this study was the observation
      that, in dogs, CK-MB activity and Tn-T content of myocardium are sufficiently
      high to be candidate serum markers for active cardiac injury.

PMID- 8989490
TI  - Effect of natural infection with minor pathogens on susceptibility to natural
      infection with major pathogens in the bovine mammary gland.
AB  - OBJECTIVE: To evaluate the effect of natural udder infection with minor pathogens
      on subsequent natural infection with major pathogens. SAMPLE POPULATION: 7 dairy
      herds with low bulk milk somatic cell count. PROCEDURE: During a 20-month
      prospective study, milk samples were collected from diary cows at regular
      intervals and from quarters with clinical signs of mastitis. Incidence of
      intramammary infection was calculated in uninfected quarters and in quarters
      infected with minor pathogens. A within-cow, matched case-control analysis was
      used to evaluate the effect of minor pathogens on subsequent infection with major
      pathogens. RESULTS: Quarters infected with minor pathogens had higher somatic
      cell count than did uninfected quarters. In quarters infected with
      Corynebacterium bovis, the rate of infection with major pathogens was lower,
      whereas in quarters infected with coagulase-negative Micrococcaceae, the rate of
      infection with major pathogens was higher than that in uninfected quarters. From
      the within-cow comparison, it appeared that, in quarters infected with minor
      pathogens, infection with major pathogens was significantly lower than that in
      comparable control quarters not infected with minor pathogens. CONCLUSIONS: Minor
      pathogens have a protective effect against infection with major pathogens. The
      protective effect of C bovis against subsequent infection with major pathogens
      appears to be greater than the effect of coagulase-negative Micrococcaceae.

PMID- 8989491
TI  - Linkage of a microsatellite marker to the canine copper toxicosis locus in
      Bedlington terriers.
AB  - OBJECTIVE: To identify a DNA marker for the copper toxicosis (CT) locus in
      Bedlington Terriers (BT). ANIMALS: 77 BT, of which 25 were affected. Diagnosis of
      affected or unaffected with CT was made in all cases by quantitative copper
      determinations on liver biopsy samples by use of established criteria. PROCEDURE:
      BT pedigrees segregating for CT were identified. Linkage studies were carried out
      using polymorphic microsatellite markers developed for the canine genome in these
      pedigrees. DNA was isolated from blood samples of pedigree members. Polymerase
      chain reaction was used to amplify and type alleles at 213 microsatellite loci in
      each dog, and findings were subjected to linkage analysis. RESULTS: One
      microsatellite marker was identified to be closely linked to CT with logarithm of
      odds score of 5.96 at a recombination fraction of zero. CONCLUSIONS: Using the
      linked marker, it has become possible to distinguish affected, homozygous normal,
      and carrier dogs in some BT pedigrees. CLINICAL RELEVANCE: In informative
      pedigrees where the marker is variable in the parents, it is possible to identify
      which dogs will require anticopper therapy and provide breeders with sound
      scientific advice about breeding strategies.

PMID- 8989492
TI  - Role of tissue factor in intra-alveolar fibrin deposition and coagulopathy
      associated with pneumonic pasteurellosis in cattle.
AB  - OBJECTIVE: To determine the role of tissue factor (TF) in the coagulation events
      leading to intra-alveolar fibrin deposition and intravascular thrombosis
      associated with pneumonic pasteurellosis in cattle. ANIMALS: Healthy 2- to 4-week
      old male Holstein calves. PROCEDURES: Blood and bronchoalveolar lavage samples
      were collected before and at 1, 2, 4, and 6 hours after inoculation of saline
      solution or Pasteurella haemolytica. Total leukocyte count, platelet count,
      plasma total protein concentration, prothrombin time, and partial thromboplastin
      time were measured in blood samples. Total nucleated cell count, total protein
      concentration, and procoagulant activity were measured in bronchoalveolar lavage
      samples. Additionally, platelet survival in blood platelet accumulation in
      affected lung tissue, and gross and microscopic lung lesions were determined.
      RESULTS: Administration of TF monoclonal antibodies (MAB) TF1-1F7 prevented the
      decrease in platelet survival and the increase in bronchoalveolar lavage fluid TF
      dependent procoagulant activity observed in calves not treated with MAB TF1-1F7
      antibody, but did not attenuate the increase in lavage fluid neutrophil numbers
      and total protein concentration, MAB TF1-1F7 administration reduced the
      percentage of lung affected by pneumonic lesions from 51.81% to 10.40% and
      attenuated intra-alveolar deposition of fibrin, neutrophils, and erythrocytes.
      CONCLUSION: Intra-alveolar fibrin deposition and activation of coagulation in
      cattle with pneumonic pasteurellosis is, at least in part, mediated by TF.
      CLINICAL RELEVANCE: Treatments that neutralize TF activity may attenuate lung
      injury in cattle with pneumonic pasteurellosis.

PMID- 8989493
TI  - Evaluation of association of blood and bronchoalveolar eosinophil numbers and
      serum total immunoglobulin E concentration with the expression of nonspecific
      airway reactivity in dogs.
AB  - OBJECTIVE: To characterize the relation between bronchoalveolar and blood
      eosinophil numbers, serum total IgE concentration, and nonspecific airway
      reactivity in healthy dogs. ANIMALS: 26 healthy Beagles. PROCEDURE: Prior to
      measurement of nonspecific airway responsiveness, dogs were anesthetized and
      bronchoscopy was performed to recover bronchoalveolar lavage (BAL) fluid.
      Repeated measurements were made in 6 dogs. RESULTS: The percentage of blood
      eosinophils varied between 0 and 13 (mean +/- SD, 5.6 +/- 3.6) %, the percentage
      of eosinophils in BAL fluid ranged between 0 and 63.5 (8.8 +/- 12.9) %, and total
      serum IgE concentration was 0.1 to 107.5 (23.4 +/- 29.1) U/ml. A strong
      association was evident between numbers of blood eosinophils and total serum IgE
      concentration (R2 = 0.413, P < 0.001), and a trend toward an association between
      numbers of blood eosinophils and numbers of eosinophils in BAL fluid was apparent
      (R2 = 0.110, P < 0.053). Significant associations were not found between any
      other aspects of the blood and BAL fluid cell profiles and total serum IgE
      concentration or airway reactivity. Serum total IgE concentration was not
      associated with airway reactivity. Further, in dogs examined on repeated
      occasions, variation in BAL fluid eosinophil numbers was not associated with any
      change in serum total IgE concentration or airway reactivity. CONCLUSIONS:
      Neither numbers of bronchoalveolar or blood eosinophils nor serum total IgE
      concentration have a significant role in determining airway reactivity in health
      dogs.

PMID- 8989494
TI  - Effects of a modified-live virus vaccine against porcine reproductive and
      respiratory syndrome in boars.
AB  - OBJECTIVES: To determine whether vaccine virus is found in serum and semen of
      vaccinated boars, whether vaccination prevents subsequent shedding of wild-type
      virus after challenge exposure, and whether semen and blood variables are altered
      after vaccination or challenge exposure with wild-type virus, or both. DESIGN:
      Throughout the 50-day postvaccination period, serum and semen from exposed boars
      were evaluated for the presence of porcine reproductive and respiratory syndrome
      virus (PRRSV). All boars were then challenge-exposed with PRRSV isolate VR-2332
      and evaluated for an additional 27 days. Semen quality variables, serostatus, and
      blood variables were monitored. ANIMALS: 7 PRRSV-seronegative adult boars.
      PROCEDURE: Semen was collected 3 times weekly and evaluated by use of a nested
      reverse-transcriptase polymerase chain reaction for detection of PRRSV RNA. Serum
      was obtained weekly and evaluated by nested reverse-transcriptase polymerase
      chain reaction, virus isolation, and PRRSV ELISA. Semen quality variables were
      evaluated 3 times weekly, and CBC was performed weekly. RESULTS: Vaccine virus
      was shed in the semen of all vaccinated boars, but shedding was of shorter
      duration in 4 of 5 vaccinated boars than that generally observed after exposure
      to wild-type virus. After challenge exposure, shedding of wild-type virus in
      semen was shortened or eliminated in 4 of 5 vaccinated boars. Percentage of
      forward movement and normal spermatozoal morphology and motility were
      significantly reduced in vaccinated boars after challenge exposure. CONCLUSIONS:
      Vaccine virus was shed in semen of vaccinated boars, but vaccination generally
      reduced or eliminated shedding of wild-type PRRSV after challenge exposure. Semen
      quality appeared to be less than optimal, particularly after vaccination and
      subsequent challenge exposure with wild-type virus. CLINICAL RELEVANCE: Extra
      label use of the PRRSV vaccine in boars remains controversial because some boars
      may still shed wild-type virus in semen after challenge exposure at
      postvaccination day 50. Semen quality also appeared to be altered after
      vaccination and subsequent challenge exposure.

PMID- 8989495
TI  - Isolation and characterization of the canine melanoma antigen recognized by the
      murine monoclonal antibody IBF9 and its distribution in cultured canine melanoma
      cell lines.
AB  - OBJECTIVE: To characterize the canine melanoma antigen recognized by the murine
      monoclonal antibody IBF9 as to its cellular location, molecular size, protein and
      glycogen contents, and distribution in cell lines. SAMPLE POPULATION: 7 cultured
      canine melanoma cell lines. PROCEDURE: Molecular characteristics of the antigen
      were determined by western blotting, enzymatic digestion studies, and tunicamycin
      inhibition studies. Distribution of the antigen in the cultured melanoma cell
      lines was determined by flow cytometry. RESULTS: The antigen consists of 2
      proteins with molecular mass of 89 and 85 kd. Tunicamycin and enzymatic digestion
      studies indicated that these proteins contained little glycosylation. Immunogold
      and immunofluorescence studies localized the antigen to the cell surface. Antigen
      expression was consistent within each cell line, with > 90% of the cells positive
      for all cell lines except 1 (80%). Percentage of positive cells and relative
      intensity of immunostaining were constant throughout all phases of the cell
      cycle. CONCLUSIONS: The antigen identified by MAB IBF9 is a well-conserved and
      highly expressed cell surface protein present during all phases of the cell cycle
      in all malignant canine melanoma cell lines examined. CLINICAL RELEVANCE: Because
      of consistency in expression, the antigen may have potential for use in dogs for
      melanoma immunodiagnostics and immunotherapy.

PMID- 8989496
TI  - Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone
      in clinically normal horses and donkeys.
AB  - OBJECTIVE: To compare plasma disposition of phenylbutazone and its metabolite
      oxyphenbutazone after i.v. administration of phenylbutazone in horses and
      donkeys. ANIMALS: 4 clinically normal horses and 6 clinically normal donkeys.
      PROCEDURE: Blood samples were collected from each animal at time 0 (before) and
      5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after i.v.
      administration of a bolus dose of phenylbutazone. Serum was analyzed in
      triplicate by use of high-performance liquid chromatography for determination of
      phenylbutazone and oxyphenbutazone concentrations. The serum concentration-time
      curve for each horse and donkey was analyzed separately to estimate model
      independent pharmacokinetic variables. RESULTS: Significant differences were
      found in several pharmacokinetic variables of phenylbutazone and oxyphenbutazone
      in horses, compared with donkeys. Mean total body clearance of phenylbutazone in
      horses was fivefold less than that in donkeys (29.3 and 170.3 ml/kg/h,
      respectively). Mean values for area under the curve and mean residence time in
      horses (118.3 micrograms/h/ml and 3.6 hours, respectively) were significantly
      greater than values in donkeys (28.3 micrograms/h/ml and 1.7 hours,
      respectively). Mean values for apparent volume of distribution at steady state
      were not significantly different between horses and donkeys. For oxyphenbutazone,
      mean time to peak concentration in donkeys was significantly less than that in
      horses (1.6 and 6.4 hours, respectively). CONCLUSION: Phenylbutazone clearance in
      donkeys was higher than that in horses, and appearance of the metabolite
      oxyphenbutazone in serum was more rapid in donkeys than in horses, indicating
      that hepatic metabolism of phenylbutazone is more rapid in donkeys than in
      horses. CLINICAL RELEVANCE: Because serum concentration of phenylbutazone after
      single i.v. bolus administration (4.4 mg/kg of body weight) decreases more
      rapidly in donkeys, compared with horses, phenylbutazone may require more
      frequent administration in donkeys to achieve therapeutic efficacy.

PMID- 8989497
TI  - Effect of treatment with erythromycin on bronchoalveolar lavage fluid cell
      populations in foals.
AB  - OBJECTIVE: To determine whether oral administration of erythromycin alters the
      inflammatory response to bronchoalveolar lavage (BAL) in young horses. ANIMALS:
      12 healthy, unweaned, mixed-breed foals of either sex, between 2 and 4 months
      old. PROCEDURE: BAL was performed; 250 ml of phosphate-buffered saline solution
      (300 mOsm, pH 7.4) was administered in 50-ml aliquots. Foals were carefully
      monitored for 4 days, then erythromycin base (25 mg/kg of body weight, PO, q 12
      h) was given to foals of the treated group. After 4 days, foals were
      reanesthetized, and the same lung was relavaged. Cytologic examination was
      performed on BAL fluid (BALF) samples from both groups of foals. At 12 hours
      after administration of the final dose, erythromycin A and anhydroerythromycin A
      concentrations were determined in plasma of treated foals. RESULTS: In the second
      BALF sample from the same lung of control foals, percentage of neutrophils was
      significantly increased (53 +/- 38.0%) [corrected], compared with that from
      erythromycin-treated foals (4.88 +/- 3.66%, P < 0.05), and was associated with
      apparent decrease in the ability of BALF cells from erythromycin-treated foals to
      migrate toward a chemoattractant source. Significantly fewer BALF cells adhered
      to a cell culture substratum after erythromycin treatment of foals. Erythromycin
      A was not detected in plasma of any treated foal at the time of the second BAL;
      anhydroerythromycin A, a degradation product of erythromycin, was detected in
      plasma of 5 of 6 foals (mean concentration, 0.2 +/- 0.06 micrograms/ml).
      CONCLUSION AND CLINICAL RELEVANCE: Bal induces neutrophilic inflammation, which
      persists for at least 4 days in the lungs of young horses. Erythromycin
      [corrected] (25 mg/kg, PO q 12 h) diminishes this inflammatory response through a
      mechanism that may involve alteration of BALF cell function. Degradation of
      erythromycin to biologically active products or presence of parent drug in
      pulmonary secretions may be responsible for alterations in pulmonary lavage cell
      chemotaxis and adherence. Erythromycin administered orally to foals at clinically
      relevant doses appears to have nonantimicrobial effects that may interfere with
      host cell metabolism and decrease inflammatory responses in airways.

PMID- 8989498
TI  - Determination of concentration of albendazole sulfoxide in plasma and uterine
      fluid of heifers.
AB  - OBJECTIVES: To determine time and concentration of peak plasma and uterine fluid
      concentrations of albendazole (ABZ) sulfoxide (ABZSO) in heifers after oral
      administration of ABZ. SAMPLE POPULATION: 25 young Angus and Simmental heifers
      maintained on pasture with ad libitum access to hay and water. PROCEDURE: Heifers
      were assigned at random to ABZ or control (water) groups, and were drenched with
      ABZ suspension at a dosage of 15, 30, 60, or 120 mg/kg of body weight, or with
      water. Plasma was collected hourly, from 14 to 25 hours after administration of
      ABZ or water. After a drug-withdrawal period, heifers were synchronized for
      estrus and drenched with 60 mg of ABZ/kg, or water (50 ml). Each uterine horn was
      flushed. All samples were extracted and subjected to high-performance liquid
      chromatography analysis. RESULTS: For all groups, highest mean +/- SEM plasma
      concentration of ABZSO was observed between 15 and 16 hours after ABZ
      administration, at 2.0 +/- 0.4 micrograms/ml (15 mg/kg), 5.3 +/- 1.0
      micrograms/ml (30 mg/kg), 7.4 +/- 1.5 micrograms/ml (60 mg/kg), and 11.1 +/- 2.7
      micrograms/ml (120 mg/kg). Mean concentration for all uterine horn fluid samples
      was 265 +/- 25 ng/ml/horn; range was 79 to 546 ng/ml/horn. The only significant
      (P = 0.0006) source of variation was the technician performing the flush. Mean
      concentration for each technician was 184 +/- 24 ng/ml/horn and 345 +/- 35
      ng/ml/horn. CLINICAL RELEVANCE: Teratogenic and embryotoxic effects of ABZSO
      differ for ewes and heifers. Albendazole sulfoxide is detectable in the uterus of
      heifers; however, ABZSO peaks in heifer plasma earlier and at a lower
      concentration than that reported for ewes, perhaps contribution to differences in
      susceptibility at similar dosages.

PMID- 8989499
TI  - Altered biological activity of equine chondrocytes cultured in a three
      dimensional fibrin matrix and supplemented with transforming growth factor beta
      1.
AB  - OBJECTIVE: To determine the effects of transforming growth factor-beta 1 (TGF
      beta 1) on the synthesis of DNA, collagen, and proteoglycans (PG) by equine
      chondrocytes. SAMPLE POPULATION: Articular cartilage obtained from multiple
      joints of a 4-month-old foal. PROCEDURE: Chondrocytes were isolated by
      collagenase digestion, cultured in monolayer, trypsinized, and implanted at a
      cellular density of 10 x 10(6) chondrocytes/ml in a three-dimensional fibrin
      matrix. Chondrocytes in culture were supplemented with TGF-beta 1 at
      concentrations of 0, 1, 5, or 10 ng/ml in serum-free medium or medium containing
      fetal bovine serum (FBS). Total PG accumulation, [35S]-labeled PG synthesis, PG
      monomer hydrodynamic size, type II collagen production, total DNA content, and
      [3H]thymidine incorporation into DNA were determined at 7 and 14 days of culture.
      RESULTS: Chondrocytes maintained a rounded phenotype, dedifferentiating slightly
      to a more fibroblastic appearance only in medium containing FBS and 10 ng of TGF
      beta 1/ml. Type II collagen immunoreaction on day 14 was decreased in the
      pericellular matrix in cultures containing FBS and 1, 5, and 10 ng of TGF-beta
      1/ml, and in all serum-free culture conditions compared to FBS and 0 ng of TGF
      beta 1/ml. Total proteoglycan accumulation and [35S]-labeled proteoglycan
      synthesis in cultures on days 7 and 14 were increased by the addition of
      exogenous TGF-beta 1 in serum-free conditions and decreased by TGF-beta 1 in FBS
      supplemented conditions. Calculation of the partition coefficients for PG
      indicated that there was synthesis of low molecular weight PG in serum-free
      conditions and larger sized proteoglycans in FBS-supplemented conditions.
      Proteoglycan molecular size was unchanged by the addition of TGF-beta 1. Total
      DNA content of chondrocytes increased with the addition of TGF-beta 1 in FBS
      supplemented conditions and decreased in serum-free conditions. CONCLUSIONS: In a
      solid three-dimensional fibrin matrix, the effects of TGF-beta 1 on chondrocyte
      biological activity depend on the culture duration and on the presence of FBS in
      the medium. Stimulatory effects of TGF-beta 1 were most pronounced in serum-free
      culture conditions with high concentration of TGF-beta 1 (5 and 10 ng/ml) on day
      7 and with low concentration of TGF-beta 1 (1 ng/ml) on day 14. CLINICAL
      RELEVANCE: TGF-beta 1 may not be a suitable growth factor for enhancement of
      equine articular grafting in sites exposed to serum.

PMID- 8989500
TI  - Plasma von Willebrand factor in thoroughbreds in response to high-intensity
      treadmill exercise.
AB  - OBJECTIVE: To determine whether plasma von Willebrand factor (vWf) concentration
      changes in horses during and after treadmill exercise. ANIMALS: 5 mature, fit
      Thoroughbreds. PROCEDURE: A blood sampling catheter was placed in the right
      jugular vein. A warm-up period was followed by a 3-minute rest period. Horses
      were galloped at racing pace until fatigued (about 2 minutes). Blood samples were
      collected prior to warm-up, during the postwarm-up rest period, 1 minute into the
      run, at cessation of the run, and 5 to 120 minutes after cessation of the run.
      vWf activity was measured by ELISA and corrected for plasma volume changes
      (measured by changes in plasma albumin concentration). Platelet-poor plasma from
      10 clinically normal, resting horses was pooled, assigned a value of 100 U/dl,
      and served as a control for all assays. RESULTS: vWf activity began increasing 1
      minute after horses reached full speed. At 5 minutes after cessation of exercise,
      vWf values had increased by mean of 92% (P < 0.05) from baseline. vWf activity
      returned baseline by 15 minutes after exercise, and remained there until 90
      minutes after exercise, when it began to increase. CONCLUSION AND CLINICAL
      RELEVANCE: The spontaneous decrease in vWf values after completion of exercise
      was unexpected because vWf has a long half-life in circulation. This unexpected
      finding is compatible with increased vWf consumption and suggests that
      microvascular trauma may occur in horses during strenuous exercise.

PMID- 8989501
TI  - Effects of naturally acquired decompensated mitral valve regurgitation on the
      renin-angiotensin-aldosterone system and atrial natriuretic peptide concentration
      in dogs.
AB  - OBJECTIVE: To investigate activity of the renin-angiotensin-aldosterone system
      and N-terminal pro-atrial natriuretic peptide (NT-proANP) during development of
      clinical signs of decompensated mitral valve regurgitation (MR). ANIMALS: 11
      Cavalier King Charles Spaniels with advanced MR attributable to chronic valvular
      disease. PROCEDURE: Dogs were subjected to repeated examinations at 6-month
      intervals until signs of decompensation had developed (end point). Data acquired
      at end point were compared with data obtained from examinations 1 year and 1 to 6
      months before decompensation. Each examination included physical examination,
      collection of venous blood, thoracic radiography, and echocardiography. RESULTS:
      Echocardiographic measurements of left atrial-to-aortic root ratio and left
      ventricular end diastolic diameter increased considerably during the study,
      whereas left ventricular end systolic diameter remained unchanged. The increase
      in cardiac size was associated with increased plasma concentration of NT-proANP.
      In contrast, plasma concentrations of aldosterone and angiotensin II were reduced
      at decompensation (aldosterone compared with the 2 earlier examinations and
      angiotensin II compared with values obtained 1 to 6 months before), despite
      decreased plasma protein concentration and hematocrit, suggesting fluid
      retention. The urine-to-plasma creatinine ratio was reduced at end point.
      CONCLUSION AND CLINICAL IMPLICATIONS: Early decompensated MR in dogs was not
      associated with increased circulating renin-angiotensin-aldosterone system
      activity, which may be caused by increased activity of ANP, and may be important
      for future therapeutic strategies of MR.

PMID- 8989502
TI  - Endotoxemia associated with experimentally induced multiple portosystemic shunts
      in dogs.
AB  - OBJECTIVE: To document presence of endotoxin in portal and systemic blood in a
      model of canine multiple portosystemic shunts (PSS), and compare values in
      clinically normal dogs, before and after vena caval banding. ANIMALS: 6 control
      dogs and 10 dogs with dimethylnitrosamine-induced multiple PSS that were
      subjected to vena caval banding. PROCEDURE: Dimethylnitrosamine was administered
      orally (2 mg/kg of body weight, twice weekly) to the 10 dogs in the diseased
      group until multiple PSS developed. Surgery was then performed on all 16 dogs
      (both groups), and shunts were confirmed in the diseased dogs. Blood was
      collected from the portal vein, hepatic vein, and caudal vena cava baseline
      endotoxin determination and aerobic and anaerobic blood culturing. Baseline
      pressure measurements were taken from the portal venous catheter; then vena caval
      banding was performed. Blood for endotoxin determinations was taken from all
      vessels 20, 40, 60, 120, 240, and 360 minutes after banding; portal pressure
      measurements were taken at the same time as sample acquisition. Blood for
      culturing was taken from the portal and hepatic venous catheters at 120, 240, and
      360 minutes after banding. RESULTS: Dogs in the diseased group had significantly
      greater overall presence of endotoxin in the portal vein (P < or = 0.0002),
      hepatic vein (P < or = 0.0001), and caudal vena cava (P < or = 0.0004) than did
      control dogs. With respect to time, endotoxin presence was greater in the
      diseased group before banding (P < or = 0.0002), and at 20 (P < or = 0.0008), 40
      (P < or = 0.002), 60 (P < or = 0.006), and 120 (P < or = 0.01) minutes after
      banding. CONCLUSIONS: Endotoxemia is more frequently present in catheterized dogs
      with dimethylnitrosamine-induced hepatic disease and multiple PSS, compared with
      clinically normal dogs. Additionally, portal pressure changes induced by vena
      caval banding did not affect endotoxemia. CLINICAL RELEVANCE: Endotoxemia may
      exist in dogs with hepatic disease and multiple PSS, and should be kept in mind
      when formulating treatment (particularly antimicrobial selection) for dogs with
      suspected endotoxemia.

PMID- 8989504
TI  - Actions of xylazine in young swine.
AB  - OBJECTIVE: To determine sedative, analgesic, and basic cardiovascular effects of
      xylazine administered to pigs. ANIMALS: 6 two-month-old Landrace x Large White
      pigs. PROCEDURE: Xylazine was administered i.v. at increasing dosages (1, 2, 4,
      8, and 16 mg/kg of body weight) to otherwise unmedicated, conscious pigs, and the
      aforementioned effects were determined before xylazine administration and 2, 5,
      10, and 15 minutes later. Then a higher xylazine dosage was given after the 15
      minute measurements were taken. RESULTS: None of the xylazine dosages induced
      sufficient analgesia to prevent painful response to tail clamping; considerable
      excitation with vocalization and without appreciable sedative effect was observed
      at all dosages. At lower dosages, cardiovascular effects were characterized by
      bradycardia and biphasic blood pressure response; initial hypertension was
      followed by hypotension. At higher dosages, severe hypotension with moderate
      bradycardia was followed by marked bradycardia and return to normal baseline
      values or slight increase in blood pressure. CONCLUSION: Xylazine did not induce
      adequate sedative or analgesic effects in pigs at any dosage tested; however,
      cardiovascular effects were considerable. These effects of xylazine differ from
      those observed in other domestic species.

PMID- 8989503
TI  - Biochemical, histochemical, and immunohistochemical characterization of distal
      tibial osteochondrosis in horses.
AB  - OBJECTIVE: To compare the biochemical, histochemical, and immunohistochemical
      profiles of articular cartilage from horses with naturally acquired distal tibial
      osteochondrosis (OC) with cartilage from a similar location in clinically normal
      horses. ANIMALS: 9 affected horses (group 1, 16 OC lesions) and 4 control horses
      (group 2, 8 normal osteochondral specimens). PROCEDURE: OC specimens were
      collected during arthroscopic removal of the fragment, and control specimens were
      collected by aseptic osteotomy. Uronic acid, total protein, total
      glycosaminoglycan (GAG), chondroitin sulfate (CS), and keratan sulfate (KS)
      contents were determined. Histomorphologic, histochemical, and
      immunohistochemical examinations were performed on specimens after snap freezing
      at -80 C and cryosectioning. Monoclonal antibodies (MAB) 3B3 and 5D4 were applied
      for location of epitopes of CS and KS, respectively. RESULTS: OC lesions had
      significantly lower quantity of uronic acid, total GAG, and CS, compared with
      normal cartilage. OC cartilage had significantly less intense staining with
      toluidine blue, along with irregular cellularity and tidemark characteristics,
      compared with normal cartilage. Monoclonal antibodies 3B3 and 5D4 stained OC
      cartilage, whereas MAB 5D4 did not stain control cartilage. Additionally, MAB 3B3
      and 5D4 stained the fibrous tissue that was found firmly attached to the OC
      lesion located between the parent distal portion of the tibia and OC fragment.
      CONCLUSION: OC cartilage lesions of the distal intermediate ridge of the tibia in
      horses are biochemically, histochemically, and immunohistochemically distinct
      from normal cartilage from the same location. Results may reflect the inability
      of the chondrocyte of the developing joint to alter matrix components that would
      allow proper maturation and differentiation into bone.

PMID- 8989505
TI  - Biochemical and site-specific effects of insulin-like growth factor I on
      intrinsic tenocyte activity in equine flexor tendons.
AB  - OBJECTIVE: To examine the site-specific and dose-dependent effects of insulin
      like growth factor I (IGF-I) on normal equine tendon in vitro. SAMPLES:
      Superficial digital flexor tendon explants derived from a euthanatized 3-year-old
      horse. PROCEDURE: Explants in culture were treated with 0, 100, 250, or 500 ng of
      IGF-I/ml for 14 days with an end-stage radiolabel of 20 microCi of [3H]proline/ml
      or 5 microCi of [3H]thymidine/ml. The tendon tissues were then analyzed
      biochemically for hydroxyproline content by reverse-phase high-performance liquid
      chromatography, DNA content by fluorometry, and glycosaminoglycan content by the
      dimethylmethylene blue dye-binding assay. In addition, morphologic analysis of
      the explants comprised histologic examination, autoradiography, and
      immunohistochemistry. RESULTS: Hydroxyproline content was significantly increased
      in explants treated with 100 and 250 ng of IGF-I/ml. Additionally, the collagen
      synthetic rate, measured by incorporation of [3H]proline into hydroxyproline, was
      significantly increased for all treatment groups. On the basis of autoradiograms,
      fibroblast proliferation and collagen synthesis were predominantly confined to
      the endcap and adjacent endotenon of the explants. Enhanced immunoreactivity for
      type-I collagen, compared with type-III collagen, was evident in the treated
      explants, an observation supported by positive staining for type-I collagen with
      picrosirius red. Histologically, treated explants contained greater numbers of
      larger and more metabolically active fibroblasts, compared with untreated
      controls. CONCLUSION: IGF-I enhances collagen synthesis in normal equine flexor
      tendon in a dose-dependent manner. IGF-I also exerts its primary effect on cell
      proliferation and collagen synthesis in the epitenon and adjacent endotenon and
      accompanying perivascular connective tissues, consistent with enhancement of
      intrinsic tendon metabolism. CLINICAL RELEVANCE: IGF-I may have a potential role
      in the treatment of tendinitis in horses.

PMID- 8989506
TI  - Environmental aspects of arsenic toxicity.
AB  - The toxicity of arsenic and its long history of use in human culture has resulted
      in widespread concern about the natural and anthropogenic levels of arsenic in
      our environment. In this article, an overview of the current environmental status
      of arsenic is presented. A brief history of the usage of this element is followed
      by a discussion of the current applications. Both natural as well as
      anthropogenic sources of input are described and discussed in terms of their
      relative impact on the Earth's environment. Numerous control mechanisms for
      arsenic exist in the environment, and the major processes involved (physical,
      chemical, and biological) are highlighted. Natural cycling of this element
      through the various environmental compartments (air, water, soil, and biota) are
      described as well as some current methods for the removal of arsenic from natural
      and industrial waters. Finally, a brief overview of the most common methods for
      the analysis of arsenic in environmental samples is presented.

PMID- 8989507
TI  - Lipoprotein(a) in health and disease.
AB  - Lipoprotein(a) [Lp(a)] represents an LDL-like particle to which the Lp(a)
      specific apolipoprotein(a) is linked via a disulfide bridge. It has gained
      considerable interest as a genetically determined risk factor for atherosclerotic
      vascular disease. Several studies have described a correlation between elevated
      Lp(a) plasma levels and coronary heart disease, stroke, and peripheral
      atherosclerosis. In healthy individuals, Lp(a) plasma concentrations are almost
      exclusively controlled by the apo(a) gene locus on chromosome 6q2.6-q2.7. More
      than 30 alleles at this highly polymorphic gene locus determine a size
      polymorphism of apo(a). There exists an inverse correlation between the size
      (molecular weight) of apo(a) isoforms and Lp(a) plasma concentrations. The
      standardization of Lp(a) quantification is still an unresolved task due to the
      large particle size of Lp(a), the presence of two different apoproteins [apoB and
      apo(a)], and the large size polymorphism of apo(a) and its homology with
      plasminogen. A working group sponsored by the IFCC is currently establishing a
      stable reference standard for Lp(a) as well as a reference method for
      quantitative analysis. Aside from genetic reasons, abnormal Lp(a) plasma
      concentrations are observed as secondary to various diseases. Lp(a) plasma levels
      are elevated over controls in patients with nephrotic syndrome and patients with
      end-stage renal disease. Following renal transplantation, Lp(a) concentrations
      decrease to values observed in controls matched for apo(a) type. Controversial
      data on Lp(a) in diabetes mellitus result mainly from insufficient sample sizes
      of numerous studies. Large studies and those including apo(a) phenotype analysis
      came to the conclusion that Lp(a) levels are not or only moderately elevated in
      insulin-dependent patients. In noninsulin-dependent diabetics, Lp(a) is not
      elevated. Conflicting data also exist from studies in patients with familial
      hypercholesterolemia. Several case-control studies reported elevated Lp(a) levels
      in those patients, suggesting a role of the LDL-receptor pathway for degradation
      of Lp(a). However, recent turnover studies rejected that concept. Moreover,
      family studies also revealed data arguing against an influence of the LDL
      receptor for Lp(a) concentrations. Several rare diseases or disorders, such as
      LCAT- and LPL-deficiency as well as liver diseases, are associated with low
      plasma levels or lack of Lp(a).

PMID- 8989508
TI  - Iron and thermoregulation: a review.
AB  - Poor temperature regulation in both human and animal models has been associated
      with iron deficiency anemia. The review examines the evidence for causality in
      both animals and humans, as well as provides an overview of temperature
      regulation in homeotherms. A number of investigations conclude that anemia is a
      central component of the inability of iron-deficient individuals to temperature
      regulate when they are cold stressed. This is apparently due to effects both on
      heat production and heat loss rates. The former is related to poor thyroid
      function in iron deficiency and the latter to the competing demands for tissue
      oxygenation vs. decreased flood flow to minimize heat losses to the environment.
      Future research needs are outlined that require integration of endocrinology,
      physiology, and nutrition disciplines.

PMID- 8989509
TI  - Volatile flavor release from foods during eating.
AB  - Classical analyses for volatile flavors (headspace or distillation/extract
      methods) give information on either the volatiles present in the air above a food
      before eating or the total volatile composition of the food. When foods are
      eaten, however, many changes take place (such as hydration/dilution with saliva,
      increase in surface area, etc.) that affect the release of volatiles from the
      food and therefore the profile of volatiles that are sensed in the nose. If we
      wish to study the relationship between flavor volatiles and the sensory
      properties of a food, it seems logical to measure the volatile profile that
      exists during eating. Although volatile flavor release during eating has been
      measured using a variety of sensory and psychophysiological analyses, only
      recently have instrumental methods been developed to measure the release of
      volatile compounds in humans as they eat. Whereas the sensory data give an
      overall measure of flavor perception, instrumental analyses can potentially
      follow the release of each and every flavor volatile and thus give a full picture
      of the aroma profiles generated during eating. From these instrumental
      measurements, a number of key factors have been identified. First, it has been
      shown that the volatile profile measured during eating is indeed different from
      the headspace profile of whole foods. Second, it is clear that the volatile
      profile in-mouth changes with time as the state of the food changes with chewing.
      Third, the volatile release from low-water foods is affected by the rate and
      extent of hydration in-mouth. The ability to measure aroma before, during, and
      after eating may lead to an understanding of the links between aroma release,
      interaction of volatiles with aroma sensors in the nose, and the overall
      perception of food flavor.

PMID- 8989510
TI  - Monoglycerides in membrane systems.
AB  - Monoglycerides are used abundantly in food systems, ingested and produced in
      vivo, and recognized as significant mediators in many biochemical processes, yet
      their function in various membrane systems is only understood at a hypothetical
      level. This paper provides a comprehensive review of the effects of
      monoglycerides in membrane systems from three diverse disciplines: nutrition,
      food science, and membrane biochemistry. An analysis of the data ranging from
      feeding studies to physical chemistry is given, detailing the role of these
      common molecules in biological membranes.

PMID- 8989511
TI  - Structures and functionalities of milk proteins.
AB  - During the last decade, marked progress has been made in the study of the fine
      details of the structures of milk proteins such as caseins, beta-lactoglobulin,
      alpha-lactalbumin, and lactotransferrin. Many of the functional properties of the
      individual milk proteins, as well as the milk protein products, may be described
      at the molecular level. This article is an attempt to thoroughly review the three
      dimensional structures of major milk proteins, and to correlate them with the
      functional aspects of these proteins as food ingredients.

PMID- 8989512
TI  - Engineering antibiotic producers to overcome the limitations of classical strain
      improvement programs.
AB  - Improvement of the antibiotic yield of industrial strains is invariably the main
      target of industry-oriented research. The approaches used in the past were
      rational selection, extensive mutagenesis, and biochemical screening. These
      approaches have their limitations, which are likely to be overcome by the
      judicious application of recombinant DNA techniques. Efficient cloning vectors
      and transformation systems have now become available even for antibiotic
      producers that were previously difficult to manipulate genetically. The genes
      responsible for antibiotic biosynthesis can now be easily isolated and
      manipulated. In the first half of this review article, the limitations of
      classical strain improvement programs and the development of recombinant DNA
      techniques for cloning and analyzing genes responsible for antibiotic
      biosynthesis are discussed. The second half of this article addresses some of the
      major achievements, including the development of genetically engineered microbes,
      especially with reference to beta-lactams, anthracyclines, and rifamycins.

PMID- 8989513
TI  - Clostridium perfringens type A enterotoxin (CPE): more than just explosive
      diarrhea.
AB  - The bacterial pathogen Clostridium perfringens is the most prolific toxin
      producing species within the clostridial group. The toxins are responsible for a
      wide variety of human and veterinary diseases, many of which are lethal. C.
      perfringens type A strains are also associated with one of the most common forms
      of food-borne illness (FBI). The toxicosis results from the production and
      gastrointestinal absorption of a protein-enterotoxin known as CPE. The
      regulation, expression, and mechanism of action of CPE has been of considerable
      interest as the protein is unique. CPE expression is sporulation associated,
      although the mechanism of cpe-gene regulation is not fully elucidated. Cloning
      studies suggest the involvement of global regulators, but these have not been
      identified. Although very few type A strains are naturally enterotoxigenic, the
      cpe gene appears highly conserved. In FBI strains, cpe is chromosomally encoded;
      whereas in veterinary strains, cpe may be plasmid-encoded. Variation in cpe
      location suggests the involvement of transposable genetic element(s). CPE-like
      proteins are produced by some C. perfringens types C and D; and silent remnants
      of the cpe gene can be found in C. perfringens type E strains associated with the
      iota toxin gene. CPE has received attention for its biomedical importance. The
      toxin has been implicated in sudden infant death syndrome (SIDS) because of its
      superantigenic nature. CPE can destroy a wide variety of cell types both in vitro
      and in vivo, suggesting that it could have potential in the construction of
      immunotoxins to neoplastic cells. It is obvious that CPE is an interesting
      protein that deserves continued attention.

PMID- 8989514
TI  - The application of quantitative risk assessment to microbial food safety risks.
AB  - Regulatory programs and guidelines for the control of foodborne microbial agents
      have existed in the U.S. for nearly 100 years. However, increased awareness of
      the scope and magnitude of foodborne disease, as well as the emergence of
      previously unrecognized human pathogens transmitted via the foodborne route, have
      prompted regulatory officials to consider new and improved strategies to reduce
      the health risks associated with pathogenic microorganisms in foods.
      Implementation of these proposed strategies will involve definitive costs for a
      finite level of risk reduction. While regulatory decisions regarding the
      management of foodborne disease risk have traditionally been done with the aid of
      the scientific community, a formal conceptual framework for the evaluation of
      health risks from pathogenic microorganisms in foods is warranted. Quantitative
      risk assessment (QRA), which is formally defined as the technical assessment of
      the nature and magnitude of a risk caused by a hazard, provides such a framework.
      Reproducing microorganisms in foods present a particular challenge to QRA because
      both their introduction and numbers may be affected by numerous factors within
      the food chain, with all of these factors representing significant stages in food
      production, handling, and consumption, in a farm-to-table type of approach. The
      process of QRA entails four designated phases: (1) hazard identification, (2)
      exposure assessment, (3) dose-response assessment, and (4) risk characterization.
      Specific analytical tools are available to accomplish the analyses required for
      each phase of the QRA. The purpose of this paper is to provide a description of
      the conceptual framework for quantitative microbial risk assessment within the
      standard description provided by the National Academy of Sciences (NAS) paradigm.
      Each of the sequential steps in QRA are discussed in detail, providing
      information on current applications, tools for conducting the analyses, and
      methodological and/or data limitations to date. Conclusions include a brief
      discussion of subsequent uncertainty and risk analysis methodologies, and a
      commentary on present and future applications of QRA in the management of the
      public health risks associated with the presence of pathogenic microorganisms in
      the food supply.

PMID- 8989515
TI  - Antioxidant defense mechanisms in parasitic protozoa.
AB  - Many of the parasitic protozoa, such as Entamoeba histolytica, Giardia,
      Trypanosoma, Leishmania, and Plasmodium, are considered to be anaerobes because
      they can be grown in vitro only under conditions of reduced oxygen tension.
      However, these parasitic protozoa have been found to be aerotolerant or
      microaerophilic, and also to consume oxygen to a certain extent. Furthermore,
      these organisms are highly susceptible to exogenous reactive oxygen species, such
      as hydrogen peroxide. They must, therefore, detoxify both oxygen and free radical
      products of enzymatic reactions. However, they lack some or all of the usual
      antioxidant defense mechanisms present in aerobic or other aerotolerant cells,
      such as catalase, superoxide dismutase, reduced glutathione, and the glutathione
      recycling enzymes glutathione peroxidase and glutathione reductase. Instead, they
      possess alternative mechanisms for detoxification similar to those known to exist
      in certain prokaryotes. Although the functional aspects of these alternative
      mechanisms are yet to be understood completely, they could provide new insights
      into the biochemical peculiarities of these enigmatic pathogens.

PMID- 8989516
TI  - Common pattern of CD44 isoforms is expressed in morphogenetically active
      epithelia.
AB  - CD44 is a widely distributed cell surface glycoprotein that is expressed as many
      isoforms arising from a single gene by alternative splicing. An important ligand
      for the widespread CD44 isoform, CD44s (standard form of CD44), is hyaluronan but
      ligands for the numerous variant isoforms are not as well characterized. Although
      it has been documented that CD44 is present at critical sites and stages of
      morphogenesis of several organs, the nature of the isoforms expressed and their
      precise localization have not been described. In this study we have determined
      the identity and distribution of CD44 isoforms expressed during development of
      several embryonic mouse organs by a combination of immunohistochemistry, in situ
      hybridization, reverse transcription-polymerase chain reaction, and DNA
      sequencing. As expected from previous studies, numerous CD44 variants are
      expressed by actively proliferating and invaginating epithelia at sites of
      epithelial-mesenchymal interaction, e.g., in the developing tooth, nose and hair
      follicle. Our results show that most prominent amongst these variants at these
      sites are CD44(v3-v10), CD44(v4-v10), and CD44(v6-v10), as was also found
      previously in the apical ectodermal ridge of the developing limb (Yu et al.
      [1996]). The common pattern of expression of these three particular variants in
      active epithelia implies that they play an important role in morphogenesis. Also
      very prominent in morphogenetically active epithelia is CD44s; hyaluronan is
      uniformly absent from these epithelia and often also from associated mesenchyme
      with which they interact, supporting the previously documented role of CD44s in
      endocytic removal of hyaluronan.

PMID- 8989517
TI  - Grg3, a murine Groucho-related gene, is expressed in the developing nervous
      system and in mesenchyme-induced epithelial structures.
AB  - We have isolated cDNAs representing multiple members of murine groucho
      homologues, designated Grg for groucho-related genes. Among them, Grg3 appears to
      produce two transcripts. One of the Grg3 transcripts contains coding sequence for
      a complete Groucho protein homologue. The second transcript contains coding
      sequence for only the two amino-terminal domains of the Groucho protein, followed
      by a hydrophobic tail and a stop codon. We analyzed the expression of both
      transcripts in mouse embryos using RNase protection and in situ hybridization.
      Expression was detected during cell determination in the nervous system and in
      somitic mesoderm, overlapping Notch1 expression and adjacent to Mash1, MyoD and
      Myf5 expression. Thus, the expression pattern of Grg3 suggests a conserved role
      in the Notch signalling pathway to regulate expression of basic helix-loop-helix
      proteins and cell determination. Grg3 expression was also consistently detected
      in epithelial structures undergoing mesenchyme induction.

PMID- 8989518
TI  - Disproportionate micromelia (Dmm) in mice caused by a mutation in the C
      propeptide coding region of Col2a1.
AB  - Mice that are homozygous for the autosomal semidominant disproportionate
      micromelia (Dmm) mutation are characterized by disproportionate micromelia,
      thoracic dysplasia, and cleft palate. Chondrocytes of the epiphyseal growth
      plates are not organized into columns, and ultrastructural analysis reveals
      excessive dilation of the endoplasmic reticulum and a paucity of collagen fibrils
      in the extracellular matrix. To map the Dmm locus, Dmm mice were crossed with the
      multiple ecotropic viral (MEV) linkage testing stock. Significant linkage of Dmm
      to the fourteen MEV linkage markers was not observed, thereby excluding
      approximately 50% of the genome as candidate regions encoding Dmm. Subsequently,
      microsatellite markers were used to assess linkage to the nonexcluded regions of
      the genome, revealing tight linkage to the locus of Col2a1, the gene encoding the
      alpha-chains of type II collagen. alpha 1(II) collagen cDNA, synthesized with RNA
      from homozygotes, was cloned and sequenced, revealing a three-nucleotide deletion
      in the region encoding the C-propeptide globular domain. The deletion leads to
      the substitution of one amino acid, Asn, in the mutant for two amino acids, Lys
      and Thr, in the wild type. Several human chondrodysplasias with similar
      phenotypes to that of Dmm are associated with defects in type II collagen. Thus,
      mice bearing the Dmm mutation serve as a model for studying the pathogenesis of
      these disorders while revealing novel insights into normal skeletal
      morphogenesis.

PMID- 8989519
TI  - Abnormal patterning of the aortic arch arteries does not evoke cardiac
      malformations.
AB  - Ablation of the cardiac neural crest results in abnormal development of the
      aortic arch arteries leading to altered patterning of the great arteries. The
      cardiac outflow tract is also affected after neural crest ablation because
      normally a subset of neural crest cells migrates from the pharyngeal region to
      form the outflow septum. Using neural crest ablation, it has not been possible to
      separate the occurrence of aortic arch maldevelopment from cardiac outflow tract
      dysmorphogenesis. In order to determine whether normal aortic arch artery
      development is a prerequisite for normal outflow tract development, we have used
      a combination of antisense treatment with backtransplantation of cardiac neural
      folds to produce abnormal patterning of the aortic arch arteries. Paralogous
      groups of Hox messages with their anterior expression domains in pharyngeal
      arches 3, 4 and 6 were targeted. Antisense targeted to paralogous group 3 Hox
      message caused aortic arch 3 located within the pharyngeal arch to regress in a
      manner similar to aortic arch 2, while antisense targeted to paralogous group 5
      Hox message caused the appearance of an additional pharyngeal arch containing a
      novel and completely independent aortic arch artery. Antisense treatment
      targeting paralogous group 4 Hox message led to no detectable cardiovascular
      phenotype in the first 6 days of development. While regression of arch artery 3
      was associated with abnormal branching patterns of the aorta and pulmonary trunk,
      this did not involve abnormal separation of the aorta and pulmonary trunks, the
      semilunar valves or the subvalvular region of the outflow tract. Because none of
      these changes in pharyngeal or aortic arch artery development was accompanied by
      abnormal development of the cardiac outflow tract, it appears that normal
      patterning of the aortic arch arteries is not a prerequisite for normal heart
      development. Using reverse transcription polymerase chain reaction (RT-PCR) we
      were unable to detect changes in any of the Hox messages except group 4, thus,
      using this particular experimental strategy, we are unable to demonstrate or
      refute that expression of hox genes by cardiac neural crest cells controls aortic
      arch patterning. Development of the cardiac outflow tract was normal in each
      instance. This suggests that abnormal aortic arch patterning does not necessarily
      lead to cardiac malformations.

PMID- 8989520
TI  - RPTP delta and the novel protein tyrosine phosphatase RPTP psi are expressed in
      restricted regions of the developing central nervous system.
AB  - Transmembrane receptor-type protein tyrosine phosphatases (RPTPs) form a novel
      and potentially important class of cell regulatory proteins. To identify RPTPs
      expressed during neural development we have characterized RPTPs transcribed in
      embryonic day (E)13.5 rat neural tube. Nine different phosphatases, one of which
      was novel, were identified. We examined the expression of the novel phosphatase,
      called RPTP psi, and of two other phosphatases, RPTP delta and RPTP mu, whose
      expression in the developing nervous system has not yet been described in detail.
      The expression of RPTP mu in small blood capillaries in developing neural tissue
      is consistent with an involvement in angiogenesis. In contrast, the temporally
      and spatially regulated expression of RPTP psi and RPTP delta in neuroepithelium
      suggests a role in early neural development. In the spinal cord, early expression
      of RPTP delta in the roof plate is followed by its expression in differentiating
      motor neurons. RPTP psi mRNA is also transiently detectable in the roof plate as
      well as in floor plate cells. In the telencephalon as well as in the hindbrain at
      E13.5, the reciprocal expression patterns of RPTP delta and RPTP psi are
      consistent with a sequential function, RPTP psi exerting its activity in
      undifferentiated progenitor cells and RPTP delta functioning during neuronal
      differentiation.

PMID- 8989521
TI  - Agrin accumulates in the brain microvascular basal lamina during development of
      the blood-brain barrier.
AB  - The blood-brain barrier (BBB) is an essential feature of the microvasculature in
      neural tissues. Agrin, a synapse organizing molecule at the neuromuscular
      junction, also accumulates on brain microvasculature and may be involved in BBB
      formation and function. We investigated the developmental expression of agrin at
      rat and chick brain capillaries by immunohistochemistry and immunoblotting. Anti
      agrin immunoreactivity (IR) completely ensheathes all observed microvessels
      labeled with anti-von Willebrand factor in adult brains of both species. Brain
      microvascular agrin IR codistributes with anti-laminin IR, consistent with agrin
      localization in the microvessel basal lamina. On microvessels in testis and
      thymus, tissues which also contain blood-tissue barriers, the pattern of IR is
      indistinguishable from brain microvessels. In contrast, little or no agrin IR is
      observed on capillaries in muscle and other tissues. During chick and rat
      development, agrin accumulates on brain microvessels around the time the
      vasculature becomes impermeable. Differential staining and electroblotting
      suggest that the agrin isoforms expressed on brain microvessels lack the 8- and
      11-amino acid sequences that confer on agrin high potency in acetylcholine
      receptor clustering. Taken in context with the organizing role of agrin in
      synaptogenesis, these results indicate that agrins may function as important
      players in the formation and maintenance of cerebral microvascular
      impermeability.

PMID- 8989522
TI  - Temporospatial expression of the small HSP/alpha B-crystallin in cardiac and
      skeletal muscle during mouse development.
AB  - Although the small (22 Kd) heat shock protein/alpha B-crystallin functions as a
      major structural protein and molecular chaperone in the vertebrate lens, little
      is known about the protein's role in nonlenticular tissues such as the heart and
      skeletal muscle. Recent studies have demonstrated that alpha B-crystallin
      expression is uniquely regulated during myogenesis in vitro. We report here for
      the first time that the temporal and spatial expression of alpha B-crystallin is
      similarly regulated in vivo during mouse embryogenesis. Expression of alpha B
      crystallin mRNA was detected by in situ hybridization in the primitive heart at
      8.5 days postconception (p.c.) and in the myotome of the somites at 10.5 days
      p.c. This tissue-restricted pattern was corroborated by immunohistochemical
      studies. alpha B-crystallin mRNA and protein expression were uniform in the
      developing atria and ventricles without regional differences or gradients. alpha
      B-crystallin expression was absent in the endocardial cushion, pulmonary trunk,
      aorta, and endothelium. Examination of muscle precursors revealed expression
      throughout the dorsoventral aspect of the myotomes and in developing skeletal
      muscle. Our findings suggest that alpha B-crystallin may serve pivotal roles as a
      structural protein and a molecular chaperone in myofiber stabilization of
      metabolically active tissues during early embryogenesis. Thus, early alpha B
      crystallin expression in myogenic lineages supports the hypothesis that the
      putative functions of alpha B-crystallin are coupled to the activation of genetic
      programs responsible for myogenic differentiation and cardiac morphogenesis.

PMID- 8989523
TI  - Control of the limb bud outgrowth in quail-chick chimera.
AB  - It is well known that the apical ectodermal ridge (AER) and the zone of
      polarizing activity (ZPA) play a major role in growth and patterning of the limb.
      But a mechanism underlying species-specific growth of the limb has not yet been
      fully elucidated. To investigate the role of AER and ZPA in limb size control, we
      constructed quail-chick limb chimeras. When we grafted a whole forelimb bud from
      one species to another, the size of the developed grafted limb was comparable to
      the limb of the donor species. Moreover, we demonstrated that neither the
      interspecific substitution of the posterior half region of the limb bud
      containing the ZPA nor the exchange of the ectodermal component of the limb
      involving the AER could alter the species-specific size of the limb. These
      results indicate that the factors affecting the size of the limb are already
      involved in the mesodermal component of the limb bud at stage 20 of chick embryo.
      Thus, the mesoderm dictates limb specificity including size.

PMID- 8989524
TI  - Each member of the Id gene family exhibits a unique expression pattern in mouse
      gastrulation and neurogenesis.
AB  - We have performed a detailed comparative in situ hybridization analysis to
      examine the patterns of expression of all the members of the Id gene family (Id1
      4) during murine gastrulation and neurogenesis. During gastrulation, both Id1 and
      Id3 are expressed in the tissues derived from the inner cell mass from 5.5 dpc
      onward, whereas Id2 is expressed in tissues derived from trophoblasts. Id4
      expression is absent during this period of development. Embryonic Id1 messages
      are detected during gastrulation on the proximal side of the embryonic ectoderm,
      which is the border between the embryo proper and the extraembryonic tissues, and
      the expression of Id3 is found throughout the entire embryo proper. This unique
      pattern of expression of the different members of the Id family suggests a
      nonredundant role for these genes in antagonizing the activity of bHLH
      transcription factors during very early mouse development. During neurogenesis,
      the expression of each member of the Id family is present in an unique pattern
      along the dorsal-ventral axis of the neural tube: In the early stages of spinal
      cord development, both Id1 and Id2 are expressed in the roof plate, whereas Id3
      is expressed both in the roof and the floor plates. As development progresses,
      the expression of both Id1 and Id3 is detected in the dividing neuroblasts,
      whereas Id2 and 4 are expressed in presumptive neurons which are undergoing
      maturation. The expression patterns of all the members of the Id gene family
      persist throughout the entire CNS, both in the spinal cord and in the brain. In
      addition, the characteristic expression of Id2 and Id4 in more mature neurons is
      reiterated both in the PNS and in the neurons of some of the sensory organs.
      These data suggest that the expression of different subgroups of the Id gene
      family may have different physiological consequences and thereby contributes in
      unique ways to specify the differentiation state of neuronal cells during
      development.

PMID- 8989525
TI  - Expression of the helix-loop-helix genes Id-1 and NSCL-1 during cerebellar
      development.
AB  - Neurons throughout the central nervous system (CNS) undergo proliferation,
      migration, and differentiation during their histogenesis. Although numerous
      regulatory molecules are expressed in developing neurons, it is unknown whether
      most of these molecules have the same function throughout the CNS or play
      different roles in different neuronal populations. Previous studies have shown
      that Id-1 and NSCL-1 are expressed at high levels in the ventricular and
      subependymal zones, respectively, of the embryonic brain. In the present study,
      the expression of Id-1 and NSCL-1 was further investigated during postnatal
      development of the cerebellum. By Northern blot hybridization analysis, the
      expression levels of Id-1 and NSCL-1 mRNA were developmentally regulated in the
      cerebellum, with the highest mRNA levels coinciding with the time of maximal
      granule cell histogenesis. By in situ hybridization, NSCL-1 mRNA was found in the
      premigratory zone of the external granule layer (EGL), a structure
      developmentally analogous to the subependymal zone of the embryonic brain. In
      normal mice, Id-1 mRNA was found to be transiently expressed in the upper
      internal granule layer (IGL), a population of cells that recently completed their
      migration from the EGL. In the mouse mutant weaver, Id mRNA was only seen in
      granule cells that have reached their normal positions in the IGL. No Id-1
      hybridization signal was observed in the large numbers of granule cells remaining
      in the EGL of weaver mice, indicating that Id-1 expression is controlled by
      spatial cues. The lack of Id-1 expression in ectopic weaver granule cells is
      compatible with previous suggestions of arrested differentiation. These results
      support the idea that transcriptional regulators of the helix-loop-helix gene
      family play important roles in neuronal development, exhibiting region-specific
      expression and function.

PMID- 8989526
TI  - Comparative analysis of AP-2 alpha and AP-2 beta gene expression during murine
      embryogenesis.
AB  - Transcription factor AP-2 has been identified as playing important roles during
      embryonic development of the neural tube, neural crest derivatives, skin, and
      urogenital tissues. Recently, we isolated a second AP-2 transcription factor, AP
      2 beta, which is 76% homologous to the previously known AP-2 alpha gene, and
      showed that both genes are coexpressed in murine embryos at day 13.5 and 15.5
      post coitum (pc). In the current study, we used specific cRNA probes to study
      comparatively AP-2 alpha and AP-2 beta expression by in situ hybridization of
      murine embryonic tissue sections. Our results reveal that expression of both
      genes starts at day 8 pc in the lateral head mesenchyme and extraembryonic
      trophoblast. The expression pattern was identical until day 10 pc but diverged
      significantly during later stages of development. From day 11 forward, specific
      expression patterns of AP-2 alpha and AP-2 beta mRNA were observed. Specific AP-2
      beta signals were detected in the midbrain, sympathetic ganglia, adrenal medulla,
      and cornea. Specific AP-2 alpha signals were present in the limb buds, dorsal
      root ganglia, tooth germs, and Moll's and Meibom's glands. In contrast,
      expression of both genes occurred in skin, facial mesenchyme, spinal cord,
      cerebellum, and renal tubular epithelia. Our results indicate that both genes are
      expressed with different temporal and spatial patterns during embryonic
      development.

PMID- 8989527
TI  - Morphological analysis of germ cell apoptosis during postnatal testis development
      in normal and Hsp 70-2 knockout mice.
AB  - The present study examined the occurrence of apoptotic cell death in the testis
      of wild-type mice from postnatal days 3 to 26 and in juvenile Hsp 70-2 knockout
      mice. Adult Hsp 70-2 knockout males are infertile and lack spermatids and
      spermatozoa (Dix et al. [1996a] Proc. Natl. Acad. Sci. U.S.A. 93:3264-3268). To
      identify the cell types undergoing apoptosis, we also examined the relationship
      between the occurrence of apoptotic cell death and the expression pattern of the
      Hsp 70-2 gene product (heat-shock protein 70-2 [HSP70-2]; marker for
      spermatocytes and spermatids), germ cell nuclear antigen 1 (GCNA1;marker for
      spermatogonia and spermatocytes), and vimentin (marker for Sertoli cells). This
      study shows that during postnatal development of the wildtype mouse testis (1)
      the percentage of apoptotic cell death detected by the TdT-mediated dUTP-biotin
      nick end labeling (TUNEL) method is higher in mice from days 8 to 22 than in
      younger or older mice, (2) the majority of apoptotic cells are spermatogonia and
      less frequently are spermatocytes, and (3) the degenerative cell death of
      spermatogonia and primary spermatocytes involves apoptosis with fragmentation of
      DNA. The analysis of apoptotic cell death in the testes of juvenile Hsp 70-2
      knockout mice showed an additional increased level of apoptosis at day 17, during
      the first wave of spermatogenesis, in pachytene spermatocytes.

PMID- 8989528
TI  - Stress decreases lymphocyte cytolytic activity in the young monkey even after
      blockade of steroid and opiate hormone receptors.
AB  - Lymphocyte cytolytic responses were assessed in 75 infant squirrel monkeys to
      investigate the influence of psychosocial disturbance on immunity. Four studies
      evaluated alterations in lytic activity during social separations from the mother
      lasting for 1-7 days. Lytic responses against target cells were markedly
      decreased during the first day of separation, and then gradually returned toward
      baseline levels. Although associated with a general lymphocytopenia in vivo,
      lower lysis was not mediated specifically by inclusion of fewer Leu11b+ cells in
      the in vitro assay. Multiple physiological processes probably converge to mediate
      the decrease in lysis. Treatment of the infant with RU486 to block corticosteroid
      hormone receptors or with naltrexone to antagonize opiate hormone action did not
      prevent the decrease in lytic responses from occurring. This research
      demonstrates that psychological disturbance can significantly impact immunity,
      but the recovery of normal functioning by 1 week also reveals the resiliency of
      the immune system, paralleling the time course of the infant's behavioral
      adaptation to this challenge.

PMID- 8989529
TI  - Visual event-related brain potentials in 4-month-old infants at risk for
      neurodevelopmental impairments.
AB  - The recording of event-related potentials (ERPs) is an electrophysiologic
      technique that has been used to evaluate the functional maturation of neural
      pathways responsible for recognition memory systems in infants and children. The
      purpose of this study was to evaluate ERP correlates of visual recognition memory
      in 4-month-old infants at risk for later cognitive impairments. We compared ERPs
      using a test of shape recognition at 4 months of age (adjusted for prematurity)
      in 16 high-risk, neonatal intensive care unit (NICU) survivors and 16 healthy
      full-term infants. ERPs were recorded while infants were familiarized with one
      stimulus (a red cross, 15 trials), then tested with 60 trials of this familiar
      stimulus and a novel stimulus (a red corkscrew). Both the NICU and control
      groups' ERPs demonstrated evidence of differential processing of the two stimuli,
      but the NICU groups' ERP patterns were distinctly different from those of the
      control group. In the NICU group, the novel stimulus elicited parietal positivity
      at 1000-1700 ms poststimulus, whereas in the control group the novel stimulus
      elicited occipital and frontal negativity at 500-1700 ms poststimulus. The ERP
      pattern demonstrated by the NICU group was atypical as it has not been previously
      described in healthy infants. The results of the study indicate that the ERP
      technique can be used to demonstrate altered patterns of neural activity during
      tasks of visual recognition memory in high-risk infants. We speculate that the
      atypical ERP patterns described in this study may indicate that patterns of
      synaptic organization were altered by neonatal events.

PMID- 8989530
TI  - The influence of natural preference for tactile stimuli on appetitive learning in
      rat pups.
AB  - Stimuli of the same modality tend to be organized along a "natural preference
      scale." This study examined the ability of six- and nine-day-old rat pups to
      acquire appetitive learning, when the CS was one of two differently "naturally
      preferred" tactile stimuli (floor textures: rug and plywood). In Experiment 1,
      all pups showed a relative natural preference for the rug texture over the
      plywood texture. Pups conditioned on the plywood texture (exposed to a sibling
      pup as the US) showed a robust increase in preference for the conditioned texture
      whereas pups conditioned on the rug texture showed a different and more moderate
      pattern of acquisition. Developmental differences were found only in extinction
      of the conditioned response: six-day-old (but not nine-day-old) pups displayed
      extinction of the response over four trials. Experiment 2 indicated that
      preexposure to the rug CS prior to conditioning (latent inhibition) did not
      interfere with the learning process on the rug texture. Two major alternative
      explanations for the differential learning patterns are discussed: motivational
      and catecholaminergic influences on learning. The results suggest that natural
      preferences may modulate early learning and memory processes.

PMID- 8989531
TI  - Instrumental learning for a thermal reinforcer in 1-day-old rats.
AB  - One-day-old rats in a cool environment (25 degrees C) quickly acquired an
      instrumental response when rewarded with a 20-s warming of the platform (from 25
      degrees C to 36 degrees C) on which they lay. The instrumental response, turning
      the head to one side, was learned within 30 min after the thermal contingency
      began and extinguished when the contingency was reversed. This experiment
      demonstrates rapid operant learning by neonates in a task that does not contain a
      Pavlovian stimulus-reinforcer contingency. The novel experimental method has wide
      applicability in psychology and neuroscience.

PMID- 8989532
TI  - Classical conditioning in the fetal rat with a long delay between presentation of
      CS and US.
AB  - A single paired presentation of the artificial nipple and milk results in
      classical conditioning of changes in perioral responsiveness in the E20 rat
      fetus. This classical conditioning is evidenced by a reduction in responding to
      perioral tactile stimulation. The results of Experiment 1 confirmed the
      specificity of milk as an unconditioned stimulus to support classical
      conditioning. Experiment 2 demonstrated that single-trial classical conditioning
      with the artificial nipple CS and milk US was possible with a delay of 30 s
      between nipple and milk presentations. Further, measurements of fetal motor
      behavior during the delay between CS and US presentations indicated that a single
      15-s presentation of the artificial nipple increased movements of the mouth for
      30 s after removal of the artificial nipple. Experiment 3 demonstrated that three
      exposures to the artificial nipple prolonged the expression of mouthing for up to
      120 s and made possible single trial classical conditioning with a delay of 120 s
      between CS and US presentations. The capacity of the fetal CNS to maintain a
      "behavioral trace" for an ecologically important stimulus, such as the nipple,
      could have adaptive significance in the early development of motivated behavior.

PMID- 8989533
TI  - The role of the anterior cingulate in automatic and controlled processes: a
      developmental neuroanatomical study.
AB  - This study examines the role of the anterior cingulate in the development of
      attention. Task performance relying predominantly on either automatic or
      controlled processes was correlated with magnetic resonance imaging based
      measures of the anterior cingulate in 26 normal children ages 5 to 16 years.
      Attentional measures were assessed with a visual discrimination paradigm.
      Parasagittal slices from a 3-D, T1-weighted volume data set were used to obtain
      area measurements of the anterior cingulate. Response latencies decreased with
      age for both tasks. There were significant correlations between attentional
      performance and right, but not left, anterior cingulate measures. Performance was
      faster and more accurate during trials requiring predominantly controlled
      processes for those children with larger right anterior cingulate measures. The
      results are consistent with adult neuroimaging findings of activation in the
      right anterior cingulate during attention tasks and with lesion studies
      implicating greater right hemisphere involvement in attentional processes.

PMID- 8989534
TI  - Infant learning and long-term memory at 6 months: a confirming analysis.
AB  - In three experiments, we tested the generality and validity of prior evidence of
      delayed recognition, memory reactivation, and retrieval specificity at 6 months
      of age using a new operant task. In Experiment 1, the forgetting function was
      found to be 2 weeks but not 3, the same as previously obtained using the mobile
      conjugate reinforcement task. In Experiment 2, a reactivation treatment with the
      original cue (train set) in the original context (room in the home) recovered the
      memory but was ineffective when either was changed. These results also confirmed
      prior findings but expanded the manipulation of context to include the place
      where training occurred. Following a reactivation treatment, infants in
      Experiment 3a failed to recognize the original cue in a different context, as
      before, but generalized to a different cue in the original context. Because the
      latter test condition was novel, a comparison group was trained in the mobile
      task and tested with a different mobile in the original context 1 day after a
      reactivation treatment (Experiment 3b); this group failed to recognize the
      mobile. The disparity in these outcomes was attributed to the salience of
      features common to the two train sets. Taken together, these findings demonstrate
      that, for the same parameters of training and testing, memory performance at 6
      months is task-independent.

PMID- 8989535
TI  - Fine-needle aspiration of inflammatory carcinoma of the breast.
AB  - Inflammatory carcinoma of the breast is an uncommon clinicopathologic entity
      which is characterized by a distinctive clinical appearance and poor prognosis.
      Histopathologically, it is characterized by plugging of dermal lymphatics with
      tumor emboli. Because this lesion usually does not form a discrete palpable mass,
      it is not as amenable to diagnosis by fine-needle aspiration (FNA) as other
      breast lesions. In the following, we report our experience with establishing the
      diagnosis of inflammatory carcinoma by FNA. Three patients underwent FNA for
      confirmation of clinically suspected inflammatory carcinoma. All aspirations were
      performed by a cytopathologist and required multiple passes to obtain diagnostic
      material. Aspirates were paucicellular and contained fragments of fibrous or
      adipose tissue. Malignant cells were predominantly distributed in tight, three
      dimensional clusters and were identifiable as tumor cells based on large size,
      nuclear irregularity, and increased nuclear to cytoplasmic ratio. Unlike
      aspirates from conventional breast carcinoma, individual dispersed cells and
      cellular discohesiveness were not prominent features. Subsequent histologic
      material from these patients revealed the characteristic tumor emboli plugging
      dermal lymphatics. We conclude that in the appropriate setting, the diagnosis of
      inflammatory carcinoma can be established by FNA.

PMID- 8989536
TI  - Cytologic features of ductal carcinoma in situ.
AB  - Fourteen cases of both palpable and non-palpable breast lesions reported as
      possible ductal carcinoma in situ (DCIS) on fine-needle biopsy (FNB) over a 12-mo
      period were retrieved from our files and compared to the subsequent histologic
      diagnosis. Although a definite cytologic pattern of highly cellular smears with
      high grade nuclei, dissociation, and background necrosis with microcalcifications
      emerged for comedo DCIS, it was not possible to differentiate these on cytologic
      grounds from high grade infiltrating carcinoma with necrosis unless mammographic
      findings were taken into account. Useful criteria for non-comedo low grade DCIS
      were high cellularity, low grade nuclei, and architectural features of papillary
      and three dimensional (3D) fragments, palisade arrangements, and monolayer sheets
      with punched out glandular lumina. We conclude that FNB has a definite role in
      the diagnosis of these lesions, with the limitation that invasive malignancy can
      never be excluded on cytologic criteria alone and clinico-radiological
      correlation is paramount.

PMID- 8989537
TI  - Cutaneous and subcutaneous masses of the chest wall: a fine-needle aspiration
      study.
AB  - Primary cutaneous and subcutaneous neoplasms of the chest wall are uncommon.
      However, metastatic tumors involving this region may be seen in local recurrence,
      widespread metastases, or as the first manifestation of an occult malignant
      neoplasm. We report a series of 81 fine-needle aspirations (FNA) of cutaneous and
      subcutaneous masses involving the chest wall of 45 males and 36 females (age
      range 32-89 yr, mean 63 yr). Sixty-nine patients (85%) have a previous history of
      malignancy. The most common sites of the primary malignancy are breast (n = 32,
      46%), lung (n = 19, 26%), head and neck (n = 6, 9%). Of these 69 aspirates, 65
      (94%) are malignant and consistent with patients' primaries; two (3%) are benign
      aspirates, and two (3%) are unsatisfactory for cytologic evaluation. The
      remaining 12 (15%) aspirates from patients with no previous history of malignancy
      reveal 10 (84%) occult malignancies, and two (16%) benign entities. The malignant
      cases consist of nine (90%) metastatic epithelial neoplasms of unknown primary
      origin, and one (10%) primary soft-tissue sarcoma. In summary, this study
      demonstrates that the majority of cutaneous and subcutaneous masses of the chest
      wall subjected to FNA are neoplastic. FNA is an effective technique for primary
      assessment of these lesions.

PMID- 8989538
TI  - Fine-needle aspiration cytology of ganglion cysts.
AB  - Ganglion cyst is a relatively common lesion resulting from mucoid, cystic
      degeneration of soft tissues adjacent to a joint space. Aspiration of cyst
      contents has been increasingly advocated as a diagnostic and, in some instances,
      therapeutic modality. We report the fine-needle aspiration cytologic (FNAC)
      findings from seven cases of ganglion cyst. These include the aspiration of
      thick, gelatinous fluid and a smear comprised of rare histiocytes embedded in a
      mucoid matrix. Although these findings are nonspecific, we believe that in the
      appropriate clinical setting, the diagnosis of ganglion cyst can be made with
      confidence by FNA.

PMID- 8989539
TI  - Fine-needle aspiration cytology in the diagnosis of superficial lymphadenopathy:
      an analysis of 2,418 cases.
AB  - During a period of 5 yr, 2,418 fine-needle aspirations (FNA) were performed on
      2,216 patients with superficial lymphadenopathy. Chronic nonspecific
      lymphadenitis was the commonest inflammatory lesion followed by tuberculosis.
      Among malignant lesions, metastatic tumors were most common followed by non
      Hodgkin's lymphoma. The FNAC findings were correlated with subsequent
      histopathological diagnosis in 1,041 cases. The sensitivity rates of FNAC in
      tuberculosis, metastatic tumors, Hodgkin's disease, and non-Hodgkin's lymphoma
      were found to be 83.3, 97, 30, and 80.3%, respectively, the specificity being
      94.3, 98.9, 98.6, and 95.4% in the same order. Immunocytochemical tests performed
      on the aspirated material helped in classifying the metastatic poorly
      differentiated tumors and confirming the diagnosis of non-Hodgkin's lymphomas.
      Effects of FNA on subsequent biopsy in 81 lymph nodes with benign hyperplasia
      were studied and showed that aspiration does not interfere with subsequent
      histologic assessment. Thus FNAC is a simple, inexpensive procedure, and when
      complemented by appropriate immunocytochemical studies is accurate and reliable
      for routine diagnosis of lymphadenopathy.

PMID- 8989540
TI  - Intraoperative consultation in ovarian lesions: a comparison between cytology and
      frozen section.
AB  - Little information is available on the relative value of intraoperative cytology
      (IOC) and frozen section (FS) in evaluation of ovarian lesions. We compared the
      two methods in 63 histologically proven cases of resected ovaries studied by
      imprints (40 cases), FNAs (38 cases), and scrapes (5 cases). Diagnoses were: 10
      nonneoplastic cysts, 46 neoplasms (benign, 19; borderline, 8; and malignant, 19)
      and 7 tumors comprised of small blue cells (SBC): granulosa cell (3), lymphoma
      (1), small cell carcinoma (1), and sarcoma (2). There were no false-positive
      diagnoses by IOC or FS among the benign and borderline conditions. Five benign
      lesions, however, had FS deferred because of architectural complexity, this in
      contrast to only one case reported as atypical by IOC. Borderline tumors were
      recognized as such in 3 cases examined by FS, but no such diagnosis was possible
      by IOC due to the inability to assess invasion. The diagnosis in borderline
      neoplasms of surface epithelial origin was deferred in 4 cases by FS and reported
      as atypical in 5 cases examined by IOC due to the spectrum of architectural and
      nuclear atypia in borderline tumors. Of the 19 malignant cases, five were
      deferred because of uncertainty of invasion by FS, whereas two were called
      atypical by IOC. Five of 7 SBC tumors were recognized as such by FS and 6 of 7 by
      IOC, but none could be unequivocally subclassified by either method.
      Intraoperative FNAs and scrapes were superior to imprints, which tended to be
      bloodier and thicker. In contrast to FNAs, scrapes were easier to direct and
      yielded greater cellularity, although both methods were comparable in diagnostic
      accuracy. Even though the diagnostic yield of IOC was only slightly better than
      that of FS, it provided much better cytologic detail, and afforded a more
      representative sampling.

PMID- 8989541
TI  - Fine-needle aspiration of nodular hidradenoma: a case report.
AB  - A case of nodular hidradenoma presenting on the forearm of a 36 year old woman is
      reported. The diagnosis was made on fine-needle aspiration biopsy (FNAB). The
      cytologic features of the lesion are described. This is the first case to be
      diagnosed cytologically.

PMID- 8989542
TI  - Papillary-cystic tumor of the pancreas.
AB  - A case of papillary cystic tumor (PCT) of the pancreas in a 40-yr-old woman is
      reported. This rare neoplasm was discovered fortuitously by a CT-scan examination
      for a palpable abdominal uterine leiomyoma. Percutaneous fine-needle aspiration
      (FNA) of the pancreatic mass was performed under CT-scan guidance. Cytologic
      examination of the material gave the diagnosis of PCT, which was confirmed by
      histologic examination of the resected tumor. Immunohistochemical staining showed
      a high degree of positivity to wide-spectrum anticytokeratin and anticytokeratin
      20, and a weak positivity to anti-NSE antibody. In addition, the tumor cells were
      highly reactive for progesterone antibody, while they were negative for estrogen.
      These findings suggest a ductal origin for PCT, and also suggest that sex
      hormones may play a role in its growth, but not in its genesis. We emphasize the
      value of FNA cytologic features in the diagnosis of these rare tumors.

PMID- 8989543
TI  - Fine-needle aspirates of granular cell lesions of the breast: report of three
      cases, with emphasis on differential diagnosis and utility of immunostaining for
      CD68 (KP1).
AB  - Fine-needle aspiration biopsy (FNA) has been recognized as a safe and reliable
      procedure for evaluating breast lesions. We herein report cytologic findings for
      needle aspirates from three granular cell nodules of the breast. The nodules were
      detected by diagnostic imaging and ranged from 0.6 to 1 cm in diameter.
      Ultrasound-guided FNA was used in all cases and revealed cellular aspirates with
      similar cytomorphologic features consisting of sheets of large granular cells
      intersected by arborizing thin-walled blood vessels. The cells had round to oval
      nuclei, inconspicuous nucleoli, and abundant, often ill-defined granular
      cytoplasm. Tissue sections of resected specimens yielded final diagnoses of
      granular cell metaplasia of histiocytes and stromal cells in one case and
      granular cell tumor (GCT) in the other two cases. FNA smears in all three cases
      were strongly positive for the lysosomal marker CD68 (KP1) and S-100 protein;
      therefore, it was not possible to distinguish true GCT from granular cell
      metaplasia/granular histiocytes. When breast aspirates reveal granular cell
      changes, excisional biopsy should be done for a definitive diagnosis.

PMID- 8989544
TI  - Detection of bladder tumor by urine cytology in cases of prostatic hypertrophy.
AB  - Routine urine cytology has been performed for 809 male patients presenting with
      symptoms due to prostatic hypertrophy. In 6.42% of the cases, bladder tumor was
      revealed incidentally diagnosed by urine cytology. Cystoscopy and bladder
      biopsies were performed to confirm malignancy. The age of these patients ranged
      from 48-84 years (mean 65.2) and they complained mainly of irritative bladder
      symptoms. It is therefore strongly indicated that all patients with prostatic
      disease should have routine cytological examination of urine sediments.

PMID- 8989545
TI  - Fine-needle aspiration biopsy of angio-immunoblastic lymphadenopathy.
AB  - In this article, we have described the fine-needle aspiration biopsy (FNAB) of
      five cases of angioimmunoblastic lymphadenopathy (AILD). FNAB of these cases
      showed large number of capillary fragments, along with polymorphous population of
      cells consisting of plenty of immunoblasts, plasma cells, eosinophils, and mast
      cells. Two cases showed clusters of clear cells. It is essential to have detailed
      clinical features for FNAB diagnosis of AILD. Histopathology is advisable in all
      the fresh cases. FNAB is helpful for screening and follow-up of AILD.

PMID- 8989546
TI  - Case of myoepithelioma originating from the palate: collagenogenesis in
      myoepithelial tumor cells.
AB  - We report a case of myoepithelioma of the palate in a 53-yr-old man.
      Myoepithelioma cells consisting of both plasmacytoid type and spindle type were
      obtained. A reticular pattern composed of a mosaic arrangement of hyaline-like
      abundant cytoplasm, and scant matrix and considerable fiber formation were
      characteristic features of the plasmacytoid type; granular cytoplasm and a snake
      like shape were characteristic features of the spindle type. These are important
      points in differentiating this tumor from cellular type pleomorphic adenoma. The
      present study shows that tumorous myoepithelial cells can synthesize and secrete
      extracellular components such as proteoglycans, basal lamina, collagen fibers,
      and elastic fibers.

PMID- 8989547
TI  - Fine-needle aspirate of primary lymphoma of bone.
AB  - Primary lymphoma of bone (PLB) is a rare bone tumor. Fine-needle aspirates (FNA)
      were done on large destructive bone tumors from 2 elderly men, and both were
      initially read as inconclusive for malignancy because of scant cellularity. On
      retrospective study of the FNA slides after examining tissue histology, low
      numbers of diagnostic cells for lymphoma were recognized on the smears. There was
      extensive crush artifact, and most intact cells were stripped of their cytoplasm.
      In neither case was enough material harvested to make cell blocks or to perform
      special studies. Tissue histology disclosed abundant fibroconnective tissue
      stroma which probably made it difficult to acquire adequate FNA specimens.
      Another FNA done on a postoperative PLB tissue specimen disclosed similar
      features. Our experience in the 3 cases is consistent with the view that even
      though smears show scant cellularity, the diagnosis of PLB can at least be
      suggested by FNA. It is therefore important not to undercall the specimen because
      of low cellularity, and recommendation for tissue diagnosis can be given. This
      process is facilitated by a high index of suspicion based on clinical and
      radiographic findings.

PMID- 8989548
TI  - Combined cytomorphologic and immunophenotypic approach to evaluation of effusions
      for lymphomatous involvement.
AB  - Combining cytomorphology and immunophenotypic data in evaluation of effusions for
      lymphomatous involvement is reliable, non-invasive, and expeditious. In this
      study, 30 effusion specimens from 30 patients with clinically suspected or
      previously diagnosed non-Hodgkin's lymphoma (NHL) were evaluated
      cytomorphologically and by flow cytometric immunophenotyping with a large panel
      of monoclonal antibodies. Of 11 patients with a previous diagnosis of NHL, 50%
      had cytomorphologic and immunophenotypic evidence of lymphomatous involvement of
      effusion specimens; therefore, flow cytometric immunophenotyping is recommended
      in these cases since there may be substantial therapeutic impact. In addition,
      69% of the effusions positive for lymphomatous involvement represented newly
      diagnosed NHL; in 36% of these cases, tissue biopsy was not necessary since they
      were either high-grade (lymphoblastic or small, non-cleaved cell type) or of the
      small lymphocytic lymphoma cell type.

PMID- 8989549
TI  - Fine-needle aspiration biopsy of adenoid cystic carcinoma of the breast: a case
      report.
AB  - We describe the cytologic findings of a fine-needle aspiration (FNA) breast
      lesion with a typical histology for adenoid cystic carcinoma. The aspirate
      yielded highly cellular smears with a monomorphic population of small, slightly
      atypical cells, arranged in multilayered groups with abundant fine intercellular
      metachromatic substance between cell groups. There were also fragments of
      fibrillar stroma in close relation to epithelial cells. The diagnosis based on
      the FNA material was suspicious of malignancy. The cytomorphology in this case
      presented a difficult differential diagnosis with pleomorphic adenoma. Features
      indicative of adenoid cystic carcinoma were nuclear cell hyperchromasia, the
      presence of small nucleoli, and scant, poorly defined, or absent cytoplasms.
      Differential diagnosis of breast adenoid cystic carcinoma with other entities
      will also be discussed.

PMID- 8989550
TI  - Fine-needle aspiration of triton tumor: morphology, immunohistochemistry,
      electron microscopy, and cell image analysis.
AB  - A single a case of malignant triton tumor, presented as a neck mass in a 34 year
      old female diagnosed solely by fine needle aspiration, is reported. The diagnosis
      was supported by immunohistochemical staining and electron microscopic
      examination that showed evidence of both schwannian and rhabdomyoblastic
      differentiation. Cell image analysis was also performed on the case and showed an
      aneuploid peak with a DNA index of 1.7. Diagnosing rare tumors with fine needle
      aspiration is feasible; particularly with the help of ancillary studies.

PMID- 8989551
TI  - Spindle-cell thymic carcinoid occurring in multiple endocrine neoplasia I: fine
      needle aspiration findings in a case.
AB  - Thymic carcinoid tumors are important to distinguish from thymomas because of
      their worse prognosis. These rare tumors occasionally occur in the setting of
      multiple endocrine neoplasia (MEN). A needle biopsy was performed on a 57-yr-old
      woman with MEN I and a newly-discovered anterior mediastinal mass. Aspiration
      smears were cellular and contained polygonal-to-spindled cells with high
      nucleocytoplasmic ratios and evenly-dispersed pattern. Occasional nuclear molding
      and rosette-like arrangements were present. A synaptophysin immunostain was
      positive on cell-block preparation. A diagnosis of thymic carcinoid was made.
      Subsequent excision of the mass confirmed the diagnosis of thymic carcinoid.
      Thymic carcinoids are cytologically similar to carcinoid tumors elsewhere. They
      should be distinguished from epithelial thymoma and substernal medullary
      carcinoma of the thyroid.

PMID- 8989552
TI  - Osteomyelitis by Paracoccidioides brasiliensis (South American blastomycosis):
      cytologic diagnosis on fine-needle aspiration biopsy smears: a case report.
AB  - A case of osteomyelitis caused by Paracoccidioides brasiliensis primarily
      diagnosed by means of fine-needle aspiration biopsy is reported here in a 60-yr
      old Italian patient who had lived in Venezuela for 40 yr. The cytologic and
      electron microscopic features of the exudate aspirated from a left femoral
      osteolytic area are described, and the differential diagnosis of this mycotic
      infection is discussed briefly.

PMID- 8989553
TI  - Squamous cells in fine-needle aspiration biopsies of salivary gland lesions:
      potential pitfalls in cytologic diagnosis.
AB  - A spectrum of neoplastic and non-neoplastic lesions of the salivary glands may
      contain squamous cells. These include chronic sialadenitis, lymphoepithelial
      cyst, pleomorphic adenoma, Warthin's tumor, mucoepidermoid carcinoma, and
      squamous cell carcinoma. The squamous cells may be a defining feature of the
      lesion, or an occasional and thus unexpected finding, with a consequent potential
      for misdiagnosis. Clinical management of these lesions differs significantly, and
      careful evaluation of the squamous elements, along with attention to other
      cellular and background components, facilitates accurate diagnosis.

PMID- 8989554
TI  - Cardiac myxoma immunohistochemistry: value of CD34, CD31, and factor XIIIa
      staining.

PMID- 8989555
TI  - Widespread intraabdominal carcinoid tumor presenting as an umbilical metastasis:
      diagnosis by fine-needle aspiration.

PMID- 8989556
TI  - The effect of selection criteria on outcome studies of children with pervasive
      developmental disorders (PDD).
AB  - The objective of this paper is to see whether regression to the mean biases the
      differences on outcome observed between children with Asperger syndrome and
      autism. Children with pervasive developmental disorders (PDD) and normal
      nonverbal IQ were divided into those with Asperger syndrome and autism. It was
      hypothesized that IQ in the autistic children would fall at the 2-year outcome
      assessments since the autistic group represented a subgroup selected on the basis
      of extreme scores on a single measure. In fact, the Asperger syndrome group
      experienced a significant drop in nonverbal IQ contrary to expectation. Serial
      measurements of nonverbal IQ at inception indicated that this drop was probably a
      function of high initial nonverbal IQ scores that fall over time due to
      increasing complexity of problem-solving tests. The results are discussed in
      relation to outcome studies of high functioning children with PDD.

PMID- 8989557
TI  - Maternal origin of inv dup(15) chromosomes in infantile autism.
AB  - Six male patients with infantile autism and an extra inverted duplicated
      chromosome 15[inv dup(15)] were reported in a previous study. These patients had
      four copies of the chromosome region 15pter-q13, or an inv dup(15)(pter-->q13;
      q13-->pter). In this new study, DNA from the families of four of the patients
      were analysed using Southern based RFLPs and microsatellite polymorphisms from
      the region. In all four cases the inv dup(15) chromosome was of maternal origin.
      Furthermore, the data suggests that it originated in the maternal meiotic process
      rather than in an early mitosis in the developmental process of the embryo. The
      extra chromosome contained material from both of the maternally derived 15
      chromosomes. Based on the molecular data presented here, a model for the origin
      of chromosome markers of this type is proposed.

PMID- 8989558
TI  - Psychosocial problems and adjustment of children with beta-thalassemia and their
      families.
AB  - This study explores the psychosocial problems experienced by families with
      children aged 6 to 14 years suffering from beta-thalassemia major (N = 188). The
      psychosocial problems and the family's adjustment to the effects of the illness
      were compared across a number of cultures where the disease is prevalent, namely
      Cyprus, Greece, and Italy. A small number of migrant children in the United
      Kingdom was also included in the study. Semi-structured interviews were conducted
      with parents who also completed the Rutter Parental Questionnaire and the
      Goldberg General Health Questionnaire. Teachers were asked to complete a
      Children's Behaviour Questionnaire designed by Rutter. In all countries the
      disease seemed to have a binding effect on the family, thus mobilizing adaptive
      mechanisms. Father's low education level and the presence of major medical
      complications were predictors of poor family adjustment. Differences between and
      within countries may well reflect differences in health policies, existing level
      of socio-economic development, and in the cultural patterns in coping with a
      chronic illness.

PMID- 8989559
TI  - Outcome of short-term child psychiatric hospitalization: teacher evaluation at 5
      month and 12-month follow-up.
AB  - This prospective follow-up study reports the outcome of children and adolescents
      discharged from short-term inpatient treatment based on teacher evaluations with
      Rutter's Questionnaire. There was a significant reduction in deviant behaviour
      between pretreatment and 5-month follow-up assessment but not between 5-month and
      1-year follow-up. However, relatively few children fell within the normal range
      of non-clinically referred children. The child's more impaired general
      functioning, more frequent individual behaviour symptoms, antisociality and
      disengaged family interaction were associated with less favourable outcome. Pure
      affective or anxiety disorder predicted functioning within normal range and
      improvement in behaviour problems at follow-up. Treatment variables were not
      found to be associated with the outcome.

PMID- 8989560
TI  - The British approach to child and adolescent psychiatry: a course for Russian
      postgraduates.
AB  - A two week course in Child and Adolescent Psychiatry was given in St. Petersburg
      as part of the partnership between the City's Child and Adolescent Psychiatry
      Service and Division of Child and Adolescent Psychiatry at Leicester University
      Medical School. In such a short course, it was necessary to focus on areas of
      particular importance to Russian practice. Areas chosen were: assessment and
      interviewing skills, psychosomatic concepts, mental retardation, suicide and self
      harm, attachment, behaviour therapy and adolescent problems. The course also
      offered practical demonstrations with Russian families. The response was
      favourable but assessment of how much the course added to knowledge was
      difficult.

PMID- 8989561
TI  - Transient psychosis in a girl with epilepsy and continuous spikes and waves
      during slow sleep (CSWS).
AB  - A normally developed and healthy 6-year-old girl suffered the onset of epilepsy
      with generalized tonic-clonic seizures and atypical absences. Initially the EEG
      showed epileptiform activity over the temporal and parietal regions, later there
      were episodes of bilateral synchronous spike-wave activity with a frequency of
      1.5-2.5 Hz. After a few months, deterioration of cognitive and behavioural
      functions appeared and gradually increased with the development of a full-blown
      disintegrative psychosis that went on for several months. Sleep EEG recordings
      showed the characteristic abnormality described as continuous spikes and waves
      during slow sleep. Later there was a remarkable improvement of neuropsychiatric
      functions but a second outbreak of psychosis seems to have left the girl, who is
      now 9 years of age, with severe mental impairment.

PMID- 8989562
TI  - Epileptic akinetic mutism: following temporal lobectomy for Rasmussen's syndrome.
AB  - A girl aged 9 years with Rasmussen's encephalitis previously treated by left
      temporal lobectomy suddenly developed prolonged attacks of extremely rapid
      respirations associated with poverty of body movements and greatly reduced facial
      movements with loss of speech. Her comprehension appeared intact and she
      responded to certain requests. Her eye gaze behaviour suggested a high degree of
      vigilance. The attacks would last from minutes to hours and were repeated up to a
      dozen times daily. In the context of the stress generated by the illness and
      other family problems the attacks had been mistaken for an hysterical
      elaboration. Their ictal nature was confirmed by EEG/video monitoring. Possible
      links with other developmental language disorders associated with epilepsy are
      discussed, including a model of autism.

PMID- 8989563
TI  - Patterns of oligodendrocyte pathology in coronavirus-induced subacute
      demyelinating encephalomyelitis in the Lewis rat.
AB  - Intracerebral infection of rats with JHM coronavirus induces a chronic
      inflammatory demyelinating disease, which in many respects mimicks the pathology
      of multiple sclerosis. We investigated the patterns of demyelination and
      oligodendrocyte pathology in this model. In early stages of the disease infection
      of oligodendrocytes was associated with a downregulation of expression of mRNA
      for proteolipid protein in the absence of myelin destruction. When demyelinating
      lesions were formed infected oligodendrocytes were destroyed by necrosis, whereas
      oligodendrocytes that did not contain detectable virus antigen or RNA were in
      part dying by apoptosis. At this stage of the disease remyelination of the
      lesions was pronounced. At later stages after infection virus antigen was nearly
      completely cleared from the lesions. In spite of the lack of detectable virus,
      ongoing demyelination and unspecific tissue destruction occurred, and
      oligodendrocytes were mainly destroyed by apoptosis. These late lesions revealed
      only minimal central remyelination, but they were frequently repaired by Schwann
      cells. Our studies suggest that the mechanisms of myelin destruction in this
      model of virus-induced demyelination are complex and that the patterns of tissue
      damage may change during the course of the disease.

PMID- 8989564
TI  - Induction of various blood-brain barrier properties in non-neural endothelial
      cells by close apposition to co-cultured astrocytes.
AB  - Vascular endothelial cells (EC) exhibit organ-to-organ heterogeneity in their
      functions and morphologies. In particular, brain capillary EC have unique
      characteristics exemplified by the blood-brain barrier (BBB). The formation and
      the maintenance of BBB have been ascribed to EC responses to inductive signal(s)
      or factor(s) from astrocytes that encircle microvessels in the central nervous
      system. These EC responses were demonstrated in numerous in vivo studies,
      exemplified by those of Janzer and Raff (Nature 325:253, 1987) and Tout et al.
      (Neuroscience 55:291, 1993) showing that transplanted astrocytes induced BBB
      properties in non-neural vascular EC. In this study, we constructed a
      heterologous co-culture system, in which rat fetal brain astrocytes were
      cultivated on one surface of a porous membrane and human umbilical vein EC on the
      opposite surface. Electron microscopic examination revealed that astrocytes
      passed their endfeet through the pores, making contact with EC. In this system,
      gamma-glutamyltranspeptidase (gamma-GTP) activity in EC was found to be
      significantly increased by contacting astrocytes in a density- and time-dependent
      manner, but not when the astrocyte feeder layer was apart from EC or replaced by
      COS cells; astrocyte-derived extracellular matrix partially activated gamma-GTP.
      mRNAs for some of the representative BBB markers, including transferrin receptor,
      P-glycoprotein, brain-type glucose transporter (GLUT-1), and gamma-GTP were also
      demonstrated by reverse transcription-polymerase chain reaction to be upregulated
      in EC co-cultured with astrocytes. Astrocyte inductions of close membrane
      apposition resembling a zonula occludens and of an increase in the content of
      mitochondria in EC were also noted in electron micrographs. Furthermore, an
      increased barrier activity against inulin was conferred on EC when they were
      lined with astrocytes. The results obtained with this heterologous co-culture
      system thus indicate that through contact with their feet, astrocytes are capable
      of transdifferentiating non-neural EC into the brain type, endowing them with the
      BBB properties.

PMID- 8989565
TI  - Expression of the S-100 proteins MRP-8 and -14 in ischemic brain lesions.
AB  - So far, microglial activation in cerebral ischemia has only been studied in
      different animal models. We have investigated the activation of microglial cells
      in human cerebral ischemia. As a marker for the activation of these "brain
      macrophages," we have used the macrophage inhibitor factor-related-proteins MRP-8
      and MRP-14, which belong to the calcium binding S-100 protein family. The
      proteins can be detected on microglial cells in bacterial encephalitis and
      Alzheimer's disease but have so far not been studied in non-inflammatory
      diseases, in which microglial activation also occurs. Antibodies against MRP-8
      and -14 detected ramified microglial cells within the first 3 days after cerebral
      infarction. Labeled cells were found selectively in the periinfarctional area. To
      support the notion that these cells belong to the locally activated resident
      microglial population, we studied their proliferation rate by staining the Ki-67
      antigen with the antibody MIB-1. Double-labeling clearly showed that in the early
      phase of cerebral infarction microglial cells in the periinfarctional area
      express MRP-8 and -14 and also proliferate. Surprisingly, MRPs are expressed no
      longer than 3 days post infarction. This indicates that the activation of the
      resident microglia is an early step of tissue reaction after cerebral infarction.
      Additionally, we found evidence that microglial cells contribute to the
      population of phagocytes only during the first 3 days post infarction. The
      majority of lipid phagocytes found in the later stages are obviously recruited
      from the blood-borne macrophage pool.

PMID- 8989566
TI  - Hippocampal loss of tenascin boundaries in Ammon's horn sclerosis.
AB  - Ammon's horn sclerosis (AHS) is a common finding in patients with temporal lobe
      epilepsy (TLE). In addition to selective neuronal cell loss and axonal
      reorganization, AHS is also characterized by a striking astroglial reaction.
      However, the functional significance of reactive astrogliosis in the pathogenesis
      of TLE remains to be determined. Reactive astrocytes produce a variety of cell
      adhesion molecules and other extracellular matrix (ECM) components with potential
      effects on axonal growth, axonal branching, and neosynaptogenesis in the central
      nervous system (CNS). In the present study we describe the distribution of the
      ECM glycoprotein tenascin/cytotactin (TN-C) in 44 human hippocampal specimens
      from patients with TLE. The distribution of TN-C immunoreactivity was evaluated
      with the anti-human TN-C monoclonal antibody K8 by densitometrical analysis, and
      TN-C protein levels were detected by immunoblotting. In the normal human
      hippocampus, there were distinctive boundaries between areas of high and low TN-C
      expression. These border zones demarcated areas with major synaptic input, i.e.,
      the dentate gyrus molecular layer (DG-ML) and the gray matter of the Ammon's
      horn. TN-C and the neurite growth-associated protein GAP-43 exhibited a
      complementary pattern of distribution. Densitometric and protein biochemical
      analysis showed a significant, 4.3-fold increase of TN-C in the hippocampus of
      TLE patients with AHS compared with normal hippocampus obtained at autopsy. This
      increase in TN-C immunoreactivity was accompanied by a loss of TN-C boundaries
      and closely correlated with the extent of reactive gliosis, as indicated by
      immunoreactivity for glial fibrillary acidic protein. Furthermore, a striking
      colocalization between TN-C and GAP-43 was observed in the DG-ML of patients with
      AHS. These observations raise the intriguing possibility of pathogenetically
      relevant glio-neuronal interactions in human TLE.

PMID- 8989567
TI  - Leptomeningeal cells modulate the neurite growth promoting properties of
      astrocytes in vitro.
AB  - Leptomeningeal cells migrate into the lesion cavity after stab wounds to the
      adult mammalian central nervous system (CNS) and interact with astrocytes that
      form a new glia limitans. However, it is not known if leptomeningeal cells alter
      the ability of astrocytes near the lesion to support axon growth. In this study,
      we have used an in vitro approach to assess leptomeningeal cell-astrocyte
      interactions in a model that resembles the interactions of these cells in vivo.
      We cultured rat cortical astrocytes on top of monolayers of leptomeningeal cells
      or astrocytes. Differences in the morphology, neurite growth promoting
      properties, and expression of various extracellular matrix molecules and beta 1
      integrin were assessed. Astrocytes acquired a long slender morphology when plated
      on leptomeningeal cells. Functionally, astrocytes cultured on top of
      leptomeningeal monolayers supported less neurite growth. Similar results were
      also obtained when astrocyte monolayers were treated with leptomeningeal cell
      conditioned medium. Quantitative immunofluorescence labeling showed a reduction
      in cell surface bound laminin on astrocytes plated on leptomeningeal monolayers.
      Qualitative assessment of the immunofluorescence labeling showed an increase in
      matrix-like deposits of tenascin-C and chondroitin sulfate proteoglycan under
      similar culture conditions. This study provides the first direct evidence that
      leptomeningeal cells reduce the neurite growth promoting properties of
      astrocytes. These results suggest that interactions with leptomeningeal cells may
      1) induce the formation of the slender astrocyte processes that form parallel to
      the lesion wall after penetrating injuries to the CNS; and 2) contribute along
      with other factors to alter astrocytes near the site of injury to a state that is
      less permissive for axon growth and regeneration.

PMID- 8989569
TI  - Lysophosphatidic acid depletes intracellular calcium stores different from those
      mediating capacitative calcium entry in C6 rat glioma cells.
AB  - Lysophosphatidic acid (LPA) functions as an extracellular lipid mediator
      stimulating phospholipase C and affecting the structure of the cytoskeleton in
      several cell types. In rat glioma C6 cells, LPA mobilizes calcium from
      intracellular calcium stores and reverts morphological changes induced by
      elevated cytosolic cAMP-concentrations. Here we show that LPA-stimulation of C6
      cells loaded with the calcium-sensitive fluorescent dye indo-1 results in calcium
      release from a subset of intracellular calcium stores that are not sensitive to
      the tumor promoter thapsigargin and do not overlap with calcium stores depleted
      during purinergic receptor stimulation with ATP. Furthermore, depletion of LPA
      sensitive calcium stores does not induce capacitative calcium entry from the
      extracellular space into the cytosol to the same extent as ATP. These results
      indicate that inositol phosphate signaling induced by LPA or ATP may differ in
      kinetics or in spatial organisation within the cell. This may represent a
      possible explanation for the previous observation that only LPA, but not other
      calcium-mobilizing agonists, reverts cAMP-induced changes in the cytoskeletal
      organization in C6 cells.

PMID- 8989568
TI  - Spinal cord dysmyelination induced in vivo by IgM antibodies to three different
      myelin glycolipids.
AB  - It was shown previously (Rosenbluth et al.: J. Neurosci. 16:2635-2641, 1996) that
      implantation of hybridoma cells that produce an IgM antigalactocerebroside into
      the spinal cord of young rats results in the development of myelin sheaths with a
      repeat period approximately 2-3x normal, similar to the abnormal peripheral
      myelin sheaths seen in human IgM gammopathies. We now present evidence that this
      effect can be reproduced in the spinal cord by implanting either of two other
      hybridomas, O4 and A2B5, that secrete, respectively, antisulfatide and
      antiganglioside IgM antibodies. The formation of expanded CNS myelin thus does
      not depend on antibodies to galactocerebroside specifically but can be mediated
      by IgM antibodies that react with other myelin glycolipids as well.

PMID- 8989570
TI  - Voltage-dependent Na(+)-HCO3- cotransporter and Na+/H+ exchanger are involved in
      intracellular pH regulation of cultured mature rat cerebellar oligodendrocytes.
AB  - Intracellular pH (pHi) was measured at 37 degrees C in mature rat cerebellar
      oligodendrocytes dissociated in culture by using the pH-sensitive probe BCECF.
      Cells were identified by anti-galactocerebroside antibody. The mean steady-state
      pHi was 7.02 in the absence of CO2/bicarbonate (Hepes-buffered solution) at an
      external pH of 7.40 and 7.04 in 5% CO2/25 mM bicarbonate-buffered solution at the
      same external pH; this value was modified neither by the removal of external
      chloride nor by the addition of the chloride-coupled transport blocker DIDS. In
      both external solutions steady-state pHi values were strongly dependent on
      external pH. In Hepes-buffered solution pHi recovery following an acid load
      required external Na+ and was completely inhibited by amiloride, indicating the
      presence of a Na+/H+ exchanger. In CO2/bicarbonate-buffered solution amiloride
      partially reduced the pHi recovery rate, indicating the presence of a bicarbonate
      dependent pHi regulating mechanism. Membrane depolarization induced by increasing
      external K+ concentration elicited an alkalinization only in the presence of
      external Na+ and bicarbonate. Analysis of the calculated HCO3- fluxes with
      respect to membrane potential indicated that these fluxes were mediated by a
      Na(+)-HCO3- cotransport with a stoichiometry of 1:3. These results demonstrate
      that a Na+/H+ exchanger and a Na(+)-HCO3- cotransporter are involved in pHi
      regulation of mature oligodendrocytes.

PMID- 8989571
TI  - Contrasting effects of mitogenic growth factors on oligodendrocyte precursor cell
      migration.
AB  - We have examined the effects of the mitogenic growth factors platelet derived
      growth factor (PDGF), basic fibroblast growth factor (bFGF) and glial growth
      factor-2 (GGF-2) on oligodendrocyte precursor migration. In an agarose drop
      migration assay PDGF and bFGF stimulated migration while GGF-2 had no effect. The
      migration-enhancing effect of bFGF cannot be blocked by neutralising antibodies
      against PDGF, confirming that this effect is direct and not mediated via
      upregulation of PDGF receptors. Based on our results, we propose a model in which
      the differing effects of PDGF and GGF-2 ensure appropriate numbers of
      oligodendrocyte precursor cells in the vicinity of axons to be myelinated during
      development.

PMID- 8989585
TI  - Primary cytotoxicity of SEB-activated human PBMC and separated CD8+ and CD4+ T
      lymphocytes elicited by two different stimulation protocols.
AB  - The primary cytotoxicity of Staphylococcal enterotoxin B (SEB)-stimulated PBMC
      and separated CD8+ and CD4+ T cells against Burkitt's lymphoma target cells has
      been characterized by applying two stimulation protocols. In the bulk protocol,
      the PBMC were stimulated with 100 ng/mL SEB for 3 days before separation to CD4+
      and CD8+ T subsets. In the direct protocol, the separated CD4+ and CD8+ T cells
      were stimulated with 100 ng SEB preabsorbed to mitomycin C (MMC)-treated APC.
      Comparison of the results of the two different protocols revealed the following
      differences: (i) PBMC in the direct protocol provided greater cytolytic activity
      than in the bulk protocol; and (ii) the CD4+ T cells acquired cytotoxicity only
      in the direct protocol. Unexpectedly, the superantigen-dependent cellular
      cytotoxicity (SDCC) of SEB-stimulated cells was not dominant compared with the
      basal cytotoxicity. The classical NK target, K-562 was also sensitive to SEB
      augmented cytotoxicity. The parallel stimulation with IL-2 and SEB caused a
      similar extent of cytotoxicity enhancement against both types of target cells.
      However, the cyclosporin A (CSA) inhibited only the SEB-induced cytotoxicity. The
      results suggest that SEB-induced PBMC acquire mainly a LAK-like cytotoxicity, as
      a consequence of newly produced lymphokines. This observation might propose a
      different approach in pathological studies.

PMID- 8989586
TI  - Cloning of the mucosal addressin MAdCAM-1 from human brain: identification of
      novel alternatively spliced transcripts.
AB  - The mucosal addressin cell adhesion molecule-1 (MAdCAM-1), expressed selectively
      on high endothelial venules (HEV) and lamina propria venules, directs lymphocyte
      traffic by binding the lymphocyte Peyer's patch adhesion molecule-1 (LPAM-1,
      alpha 4 beta 7). Full-length DNA encoding human MAdCAM-1 was obtained by
      combining sequences from an expressed sequence tag (EST) identified in an early
      stage human brain cDNA library, a polymerase chain reaction-derived clone, and a
      MAdCAM-1 genomic clone. The deduced amino acid sequence revealed an 18 amino acid
      signal peptide, two N-terminal immunoglobulin (Ig)-like domains conserved (59
      65%) in sequence with those of the mouse homologue, an 86 amino acid mucin-like
      region rich in serine-threonine residues, a 20 amino acid transmembrane domain
      and a 43 amino acid charged cytoplasmic domain. No counterpart to the third IgA
      like domain of mouse MAdCAM-1 was present; however, the serine-threonine-rich
      mucin domain was extended as two distinguishable major and minor mucin regions
      unrelated to the mouse domain. The major domain is formed from six tandem repeats
      of an eight amino acid sequence having the MUC-2-related consensus DTTSPEP/SP.
      Human MAdCAM-1 mRNA transcripts were restricted to small intestine, colon,
      spleen, pancreas and brain. Alternatively spliced MAdCAM-1 variants were
      identified that lack parts of the second Ig domain and all or part of the major
      mucin domain, indicating that the function of this vascular addressin is
      regulated by extensive modifications to its multi-domain structure.

PMID- 8989587
TI  - An in vivo mammary infusion model for tissue migration of leucocytes during
      inflammation.
AB  - Infusion of LPS or nematode larvae into the mammary glands of sheep induces
      recruitment of neutrophils or eosinophils respectively. While neutrophil
      recruitment required only a single infusion of LPS, repeated infusions of
      parasite larvae were required to induce significant eosinophil migration into the
      lumen of the glands. Eosinophil recruitment was accompanied by a distinct
      population of lymphocytes consisting mainly of activated (MHC class II and CD25+)
      T cells. L-selectin was expressed at reduced levels on both neutrophils and
      eosinophils collected from the mammary gland compared with cells present in the
      blood of the same sheep. In addition, VLA-4 and beta 1-integrin were down
      regulated or negative in mammary eosinophils compared with strong expression in
      the blood while neutrophils were negative for these markers in both mammary
      washes and blood. Eosinophils in blood and mammary glands were negative for MHC
      class II, CD25 and CD4. Mast cells and lymphocyte aggregates were present in the
      tissue of glands chronically stimulated with parasite larvae while eosinophils
      were only present if the gland had been recently stimulated. These studies show
      that detailed in vivo analysis of leucocyte migration can be easily performed in
      the sheep mammary infusion model which allows non-invasive and repeated sampling
      of inflammatory cells before and after tissue migration.

PMID- 8989588
TI  - Molecular basis of immune evasion strategies by adenoviruses.
AB  - Human adenoviruses have provided valuable insights into virus-host interactions
      at the clinical and experimental levels. In addition to the medical importance of
      adenoviruses in acute infections and the ability of the virus to persist in the
      host, adenovirus-based recombinants are being developed as potential vaccine
      vectors. It is now clear that adenoviruses employ various strategies to modulate
      the innate and the adaptive host immune defences. Adenovirus genome-coded
      products that interact with the immune response of the host have been identified,
      and to a large extent the molecular mechanisms of their functions have been
      revealed. Such knowledge will no doubt influence our approach to the areas of
      viral pathogenesis, vaccine development and immune modulation for disease
      management.

PMID- 8989589
TI  - Masters of deception: a review of herpesvirus immune evasion strategies.
AB  - Herpesviruses have acquired a variety of different mechanisms to avoid the
      damaging effects of host immunity. Frequently, these viruses subvert normal
      immune regulatory functions utilized by the host. The focus of this review is
      upon herpesvirus genes encoding known or potential immunomodulatory proteins.
      Areas covered include inhibition of complement and antibody function, herpesvirus
      encoded homologues of cytokines and chemokine receptors, and potential disruption
      of cellular recognition of virally infected targets.

PMID- 8989590
TI  - Mechanisms of interference with the MHC class I-restricted pathway of antigen
      presentation by herpesviruses.
AB  - Herpesviruses are an ancient, ubiquitous family of DNA viruses, most of which
      share a lifestyle of latently or persistently infecting a young host, and
      spreading to infect a new host a generation later. Most herpesviruses interfere
      with antigen presentation via the MHC class I-restricted pathway of antigen
      presentation, suggesting that impairment of the cytotoxic T lymphocyte response
      is necessary for the maintenance of this lifestyle. The diverse molecular
      mechanisms that have so far been discovered employed by Epstein-Barr virus,
      herpes simplex viruses, and human and murine cytomegaloviruses are described in
      this review.

PMID- 8989591
TI  - Evasion of apoptosis by DNA viruses.
AB  - Apoptosis is a form of cell death distinct from necrosis which plays an important
      role in processes such as homoeostasis and the elimination of damaged cells. It
      can be triggered by a variety of stimuli including DNA damage and cytotoxic T
      lymphocyte activity, both of which may be induced in the course of a viral
      infection. Initially, induction of apoptosis may occur through pathways which
      have also been shown to be activated on disturbance of the cell cycle or damage
      to cellular DNA. At later time points during the course of infection, apoptosis
      can also be triggered by cytokines and immune effector cells. Apoptosis of the
      host cell before the completion of the viral replication cycle may limit the
      number of progeny and the spread of infection. The importance of apoptosis as an
      antiviral defence is illustrated by the presence of multiple pathways for
      apoptosis induction and inhibition in both the host and virus. In this review,
      the inhibition of apoptosis is described in adenovirus and poxvirus infection.
      These examples illustrate two of the divergent paths by which viruses may avoid
      the apoptotic response.

PMID- 8989592
TI  - M-T2: a poxvirus TNF receptor homologue with dual activities.
AB  - Poxviruses are experts at manipulating and evading the host's immune response.
      They have acquired a number of open reading frames which specifically confer
      direct anti-immune properties, either by mimicking cytokine receptors and growth
      factors or by disarming cytokine regulatory cascades. The Myxoma T2 protein (M
      T2), a TNF receptor homologue, is secreted from virus infected cells and can bind
      TNF-alpha with high affinity, and thereby inhibit TNF-alpha-mediated
      cytotoxicity. M-T2 also acts to inhibit virus-induced lymphocyte apoptosis by an
      as yet undefined mechanism. As such, T2 constitutes a significant virulence
      factor for poxviruses, influencing the outcome of infection, both in vitro and in
      vivo.

PMID- 8989593
TI  - Antigenic variation and immune evasion in Plasmodium falciparum malaria.
AB  - Plasmodium falciparum malaria is responsible for 2 million deaths each year. Even
      in endemic regions, immunity to malaria builds slowly and is rarely complete.
      Strategies such as antigenic variation and antigenic diversity are critical to a
      parasite's ability to evade the host immune response and infect previously
      exposed individuals. In this short review, the phenomenon of antigenic variation
      is discussed in relation to immune evasion and its impact on parasite
      pathogenesis. Recent advances in the understanding of the underlying molecular
      mechanisms of antigenic variation are examined and questions posed for future
      research.

PMID- 8989594
TI  - Regulation of host cell function by glycosylphosphatidylinositols of the
      parasitic protozoa.
AB  - Antigenic variation, antigenic drift, molecular mimicry, intracellular
      localization and sequestration in privileged sites are important mechanisms of
      immune evasion by infectious organisms. Added to this however is the phenomenon
      by which pathogens deliberately regulate host cell function by the production of
      glycolipids with agonistic or antagonistic signal transduction capacity. Such pro
      active glycolipids are often pathogenicity factors, but they also serve as
      immunomodulators and immunosuppressants, and these activities may serve as
      mechanisms of immune evasion. Here we review glycosylphosphatidylinositols and
      related structures, a novel class of glycolipid common to eukaryotic parasites
      and their hosts, which recent studies suggest may play a role in immune evasion
      and immunosuppression by regulating host cell function via the activation or
      suppression of endogenous host signalling pathways.

PMID- 8989595
TI  - Defence against the immune barrage: helminth survival strategies.
AB  - Parasites have generated a range of countermeasures against the host immune
      system which allows their survival long enough for reproduction to occur.
      Parasite subsistence is enhanced by evasion of the immune response utilizing
      mechanisms such as antigenic variation of exposed immunogenic proteins, shedding
      of surface proteins which are the target of an immune response, and protease
      production to neutralise specific anti-parasite immune components. Recent
      advances in the fields of immunology and parasitology have highlighted a range of
      mechanisms by which the parasite actively modulates the immune response to allow
      survival. Parasite factors can directly suppress the function of certain subsets
      of immune cells as well as stimulating other cell populations which have
      suppressive activity. Strategies such as the skewing of the type 1-type 2
      cytokine profile to that of a less appropriate response, and the mimicry of host
      immune regulatory proteins are becoming more widely acknowledged as means by
      which helminths enhance their survival. An illustration of the extent by which
      parasites can exploit host immune components is emphasized by the use of host
      cytokines as parasite growth factors. This review will examine some of the
      strategies developed by helminths which enables them not only to survive in the
      host, but also to prosper.

PMID- 8989596
TI  - Fungal keratitis.

PMID- 8989597
TI  - Herpesvirus infections of the anterior segment.

PMID- 8989598
TI  - Parinaud's oculoglandular conjunctivitis and cat-scratch disease.

PMID- 8989599
TI  - Adjunctive therapy and surgical considerations in the management of bacterial
      ulcerative keratitis.

PMID- 8989600
TI  - Parasitic infections of the anterior segment.

PMID- 8989601
TI  - Late infections associated with glaucoma surgery.

PMID- 8989602
TI  - Endophthalmitis following glaucoma filtering surgery.

PMID- 8989603
TI  - Postoperative infection following current cataract extraction surgery.

PMID- 8989604
TI  - Postoperative endophthalmitis: risk factors and prophylaxis.

PMID- 8989605
TI  - Cytomegalovirus retinitis.

PMID- 8989606
TI  - Acute retinal necrosis syndrome: findings, management, and differential
      diagnosis.

PMID- 8989607
TI  - Endogenous fungal endophthalmitis.
AB  - Endogenous fungal endophthalmitis has increased in the past half-century because
      of the advent of antibiotics and indwelling catheters. The disease process can
      produce highly suggestive, though nonpathognomonic, ocular signs that assist the
      clinician in reaching a diagnosis. Intraocular inflammation, especially if it is
      granulomatous in nature in a patient with one or more of the risk factors already
      discussed, should raise the suspicion of fungal endophthalmitis. If a diagnosis
      remains elusive, vitreous biopsy is indicated for proper identification of a
      fungal organism. Although a particular therapeutic regimen has not yet been
      prospectively established, compelling arguments can be made to treat nearly all
      patients with endogenous fungal endophthalmitis with a systemic antifungal such
      as amphotericin B or fluconazole. A possible exception includes an IVDA-related
      endophthalmitis in a patient with negative blood cultures and without other
      evidence of fungemia. Vitrectomy and intravitreal amphotericin B (with or without
      intravitreal corticosteroid) should be considered in cases of endogenous fungal
      endophthalmitis in which there is substantial vitreous involvement, and also in
      cases in which there is clear progression of disease despite initial therapy with
      an appropriate systemic antifungal agent. Prompt therapy following early
      diagnosis will help reduce significant visual loss in all forms of fungal
      endophthalmitis.

PMID- 8989608
TI  - Rare causes of endophthalmitis.
AB  - Endophthalmitis is a potentially devastating disease that requires aggressive
      management. While endogenous and exogenous endophthalmitis both remain uncommon,
      a great deal has been written about their management. However, most current
      knowledge is based on experience with the most common forms of endophthalmitis:
      (1) postoperative cases due to coagulase-negative Staph, Staph aureus, and Strep
      pneumoniae; and (2) endogenous cases due to nongroup B Strep, Staph species,
      Candida species, and other fungi. Cases that are unusual in terms of their
      presentation and/or their causes do occur, and the physician caring for a patient
      with endophthalmitis should be aware of these forms of endophthalmitis to aid in
      making the correct diagnosis and applying any treatments that have been reported
      to be effective. We believe that further studies will aid in the recognition and
      treatment of many of the unusual forms of endophthalmitis and hope that in the
      future patients afflicted with these difficult problems will enjoy better
      prognoses.

PMID- 8989609
TI  - Ocular histoplasmosis.

PMID- 8989611
TI  - Infectious optic neuropathy.

PMID- 8989610
TI  - Infectious choroiditis in the acquired immune deficiency syndrome.

PMID- 8989612
TI  - Potential sources for orbital cellulitis.

PMID- 8989613
TI  - Molecular pathological diagnosis of ocular infections.

PMID- 8989614
TI  - Mechanisms of nerve cell death: apoptosis or necrosis after cerebral ischaemia.

PMID- 8989615
TI  - Changes in ionic fluxes during cerebral ischaemia.

PMID- 8989616
TI  - Techniques for examining neuroprotective drugs in vivo.

PMID- 8989618
TI  - Calcium antagonists: their role in neuroprotection.

PMID- 8989617
TI  - Techniques for assessing neuroprotective drugs in vitro.

PMID- 8989619
TI  - Sodium and potassium channel modulators: their role in neuroprotection.

PMID- 8989620
TI  - NMDA antagonists: their role in neuroprotection.

PMID- 8989621
TI  - Development of the NMDA ion-channel blocker, aptiganel hydrochloride, as a
      neuroprotective agent for acute CNS injury.

PMID- 8989622
TI  - Pharmacology of AMPA antagonists and their role in neuroprotection.

PMID- 8989623
TI  - GABA and neuroprotection.

PMID- 8989624
TI  - Adenosine and neuroprotection.
AB  - In summary, there is good evidence that adenosine is an endogenous
      neuroprotective agent. Probably several mechanisms can contribute to this effect
      and the relative importance of these mechanisms may depend on the type of
      ischaemia. There is also evidence that drugs that affect adenosine may be used
      therapeutically. An important caveat is that acute and long-term effects of
      adenosine receptor agonists and antagonists differ widely. This effect inversion
      suggests that drugs that affect adenosine receptors also induce important
      adaptive events in the central nervous system. Such adaptive effects may also be
      evident in the case of other agents, which emphasizes that the long-term
      usefulness of a therapeutic strategy cannot always be judged only from acute
      studies.

PMID- 8989625
TI  - Interleukins and cerebral ischaemia.

PMID- 8989626
TI  - Nitrone-based free radical traps as neuroprotective agents in cerebral ischaemia
      and other pathologies.
AB  - Nitrone-based spin trapping compounds have been shown to protect experimental
      animals from pathology associated with ischaemia/reperfusion injury,
      endotoxaemia, natural and accelerated aging, certain xenobiotics, and physical
      trauma. Moreover, these compounds have an intriguing nootropic action. Nitrones
      affect pathophysiological correlates in both the central nervous system and
      peripheral organ systems. These compounds have been shown to affect cellular
      oxidation state and oxidatively sensitive enzyme systems, but the precise mode of
      nitrone action has not been elucidated. Recent discoveries regarding the ability
      of nitrones to suppress gene transcriptional events associated with
      pathophysiological states, particularly the elaboration of NF kappa B-regulated
      cytokines and inducible nitric oxide synthase, argue that nitrones may act at a
      proximal level to oxidatively sensitive signal amplification systems.

PMID- 8989628
TI  - A review of earlier clinical studies on neuroprotective agents and current
      approaches.

PMID- 8989627
TI  - Neurotoxic and neuroprotective roles of nitric oxide in cerebral ischaemia.

PMID- 8989629
TI  - A beleaguered profession yearning for Lincolns: the need for visionary leadership
      in the health care profession.
AB  - In the current milieu of monumental change in medicine and the health sciences,
      effective leadership is needed from within the health care profession to address
      various challenges. A leader needs to be visionary, and must possess the ability
      to share this vision with others through effective communication. The leader
      should be fair, trustworthy, sincere, truthful, honest, courageous, and
      compassionate. He or she should be strong and resolute and be able to lead
      through persuasion rather than coercion. The leader should possess the attributes
      and skills to mold organizational change in the desired direction and to deal
      with reactions of individuals going through the change process. The democratic
      style of leadership appears to be the most effective, although the autocratic
      style may be needed occasionally to accomplish a specific task. The noncentered,
      laissez-faire style of leadership is generally not effective and results in
      significant frustration among subordinates. The most desirable type of power a
      leader can exercise over subordinates results from deep trust and effective
      communication, which make people follow the leader willingly. The health care
      profession needs to solicit the help of experienced members who have shown
      leadership to help guide various activities and to serve as mentors for the less
      experienced individuals. Special courses should be designed and implemented to
      develop specific leadership skills, which are applicable to various health care
      disciplines. Practical teaching models, including individuals from various
      disciplines working together in teams, with opportunities for leadership, should
      be implemented. Also, an appropriate culture that recognizes and rewards
      effective leadership in academe needs to be established within academic
      institutions.

PMID- 8989631
TI  - Faculty development--general or specific, local or national? The content and
      organization of faculty development in The Netherlands.

PMID- 8989630
TI  - The 1996 Margaret Hay Edwards Achievement Medal.

PMID- 8989632
TI  - Teaching efficacy of a medical education module on genetic testing for cancer.
AB  - BACKGROUND: With the identification of the breast cancer susceptibility genes
      BRCA1 and BRCA2, clinical testing for detection of the mutated genes may be
      available in the near future. Primary care physicians increasingly serve as full
      service providers and gatekeepers and must be aware of presymptomatic testing in
      order to counsel their patients appropriately. To address this educational need,
      a new module was incorporated into the genetics course taken by first-year
      medical students at the Medical College of Virginia. METHODS: The module used
      small groups, led by genetics faculty and members of the Virginia Breast Cancer
      Foundation, for discussion of case examples. The medical students' knowledge of
      and attitudes toward cancer and predictive genetic testing were assessed by a
      pretest and a posttest. RESULTS: After the module, knowledge scores increased by
      27%, and significant changes were seen in the students' attitudes toward issues
      such as the regulation of testing availability and the psychological effect of
      testing. Most students consistently felt that predictive genetic testing is
      beneficial, that they would have the testing themselves, that genetic counseling
      should be required for testing, and that insurers' access to genetic testing
      results should be limited. Overall, the module was received favorably by all
      participants. CONCLUSIONS: Small-group discussion of relevant case examples
      increases knowledge and awareness of issues regarding presymptomatic genetic
      testing for breast cancer.

PMID- 8989633
TI  - The advanced practice nurse: meeting the information needs of the rural cancer
      patient.
AB  - BACKGROUND: The goal of the Rural Cancer Care Project is to assist patients and
      families residing in rural areas to receive the highest-quality cancer care in
      their own communities. METHODS: An advanced practice nursing clinic, serving as
      an adjunct service to specialty cancer care, is the core of the intervention
      model demonstrated by the "Rural Partnership Linkage for Cancer Care", a National
      Cancer Institute grant awarded to Michigan State University in 1990. The nursing
      intervention is directed to meeting patient and family needs. RESULTS: One
      hundred seventy patients enrolled in the study beginning in January 1993 through
      September 1995. Knowledge deficit proved to be one of the most frequently
      identified problems (in 78% of the 170 patients evaluated), although the patient
      and family had often received care at a community oncology center with specialist
      health care professionals. Teaching was a major nursing intervention employed in
      patient care to address patient problems and needs as presented (e.g., chronic
      pain, fatigue). The data also demonstrated that the patients had more knowledge
      needs in the later stages of disease when they had cancers in all sites but the
      breast, where patients with Stage I and II disease had the greater learning
      needs. CONCLUSIONS: Nursing interventions were directed primarily at education
      regarding cancer as a disease or the understanding of chemotherapy. The advanced
      practice nurse, by providing direct patient and family education in a community
      setting, does improve patient knowledge and subsequent outcomes.

PMID- 8989634
TI  - Increasing mammography and breast self-examination in African American women
      using the Witness Project model.
AB  - BACKGROUND: The five-year survival rate for African American women with breast
      cancer is notably lower than the rate for white women; thus, appropriate cancer
      education and screening efforts are needed to increase mammography and breast
      self-examination practices by African American women. METHODS: The Witness
      Project is a theory-based intervention designed to provide culturally sensitive
      messages, from African American breast cancer survivors, in churches and
      community organizations. These messages emphasize the importance of early
      detection to improve survival. RESULTS: Intervention research in eastern Arkansas
      with 204 African American women demonstrated a significant increase in the
      practice of breast self-examination (p < 0.001) and mammography (p < 0.001) after
      participation in the Witness Project. There was no significant difference between
      the pre- and postintervention scores for scaled items for the health-belief model
      and locus of control. CONCLUSIONS: Results demonstrate that culturally
      appropriate cancer education programs are able to change behavior by meeting the
      beliefs of participants rather than attempting to change their beliefs.

PMID- 8989635
TI  - Use of a photoessay to teach low-income African American women about mammography.
AB  - BACKGROUND: Although incidence rates of breast cancer are lower among African
      American women than white women, mortality rates among African American women are
      higher, especially for women of lower socioeconomic levels. Reasons for this
      situation include the lesser use of breast cancer screening examinations by low
      income, primarily African American women, late stage of diagnosis, and delays in
      treatment. METHODS: As part of community outreach and public health clinic
      inreach programs for the Forsyth County Cancer Screening Project, approximately
      908 African American women who reside in low-income housing communities were
      targeted for educational efforts related to breast cancer screening. Early in the
      project, it was discovered that many of the women were unfamiliar with
      mammography and had very little awareness of how the entire examination was
      conducted. This low level of knowledge was particularly important because it was
      a barrier for obtaining regular mammography. A photoessay depicting the process
      of getting a mammogram was developed and used in community outreach efforts in
      three formats: in educational classes, as a display in the housing communities,
      and in physicians' offices. The acceptability of this photoessay to communicate
      knowledge of and reduce fears about mammography was assessed through evaluation
      surveys in interviews with a sample of 47 women from the target population.
      RESULTS: Overall, these women liked the photoessay and felt that it provided
      knowledge about mammography and reduced fears associated with anticipating
      mammography. CONCLUSIONS: Strategies such as this may be ideal to communicate
      important information about cancer prevention and control in low-literacy
      populations.

PMID- 8989636
TI  - Breast cancer screening practices among Cambodian women in Houston, Texas.
AB  - BACKGROUND: Faced with Western medicine and a health care system that is
      unfamiliar, Cambodian women experience barriers to breast cancer prevention
      activities and thus are seldom reached through current breast cancer education
      and prevention activities. This study examined the knowledge, attitudes, and
      practices of breast cancer screening among Cambodian women in Houston, Texas.
      METHODS: Two hundred sixteen Cambodian women aged 18 years or older were surveyed
      by telephone. RESULTS: Logistic regression analysis identified five variables as
      significant predictors of ever having had a clinical breast examination:
      perceived barriers to clinical breast examination, income, written-language
      acculturation, knowledge about clinical breast examination recommendations, and
      education in the United States. Education and knowledge of mammography were found
      to be important predictors of mammography. Language acculturation variables were
      not associated with ever having had mammography. CONCLUSIONS: The rate of breast
      cancer screening among Cambodian women in Houston is lower than that for all
      women in the United States. These results underscore the importance of developing
      culturally and linguistically appropriate breast cancer prevention activities for
      Cambodian women, who face cultural and language barriers to traditional services.

PMID- 8989637
TI  - Health beliefs and alternative medicine: a qualitative study of breast cancer
      patients.
AB  - BACKGROUND AND METHODS: To explore beliefs among patients who use alternative
      medicine, the authors interviewed 20 female breast cancer patients for their
      perceptions of health, illness, and medical care. The participants had used
      either conventional therapies alone (conventional group, n = 11) or conventional
      with alternative therapies (unconventional group, n = 9). RESULTS: Beliefs about
      the cause of illness were similar between groups, whereas beliefs about recovery
      showed greater variation. In addition, the patients in the unconventional group
      perceived their beliefs to be recently formed and chiefly influenced by their
      cancer experiences, while the patients in the conventional group felt that their
      beliefs were "lifelong" and influenced primarily by upbringing. CONCLUSIONS:
      Beliefs about health and illness represent an evolving process related to changes
      in the way patients understand their illness over time. Discussing patients'
      beliefs in the clinical setting may help physicians better understand patients'
      choices with regard to medical care.

PMID- 8989638
TI  - Assessment of knowledge, attitudes, and behaviors relative to cervical cancer and
      the Pap smear among adolescent girls in West Virginia.
AB  - BACKGROUND AND METHODS: Questionnaires assessing knowledge of, attitudes toward,
      and behaviors relative to cervical cancer and its prevention were administered to
      279 tenth-grade girls. RESULTS: Eighty-four percent had heard of cervical cancer,
      and 83% had heard of the Pap smear. Sexual intercourse with multiple partners and
      cigarette smoking were risk factors identified by 65% and 40% of these students,
      respectively. Forty-eight percent reported being sexually active. This group,
      compared with those not sexually active, was more likely to 1) identify the Pap
      test as a test involving a vaginal examination, 2) use tobacco products, and 3)
      be exposed to tobacco smoke. The most common barriers to obtaining a Pap test
      reported by those sexually active were embarrassment (64%), pain/discomfort
      (57%), fear of cancer (27%), fear of parents discovering sexual activity (25%),
      and cost (13%). CONCLUSIONS: Based on the information obtained in this study, the
      authors recommend changes in school health programs that target adolescent girls:
      1) risk factors and behavior should receive more emphasis, and 2) the pelvic
      examination and Pap test should be described in sufficient detail to address the
      issues of embarrassment, pain, and discomfort.

PMID- 8989639
TI  - A psychoeducational bereavement-support group for families provided in an
      outpatient cancer center.
AB  - BACKGROUND: Grief is a normal and highly personal reaction to loss. Bereavement
      care (individual and/or group) can assist family members and friends in coping
      with their feelings of grief, thereby reducing the possibility of complicated
      grief reactions. The families and significant others of patients who have died in
      settings other than a hospice do not automatically have the opportunity for
      bereavement follow-up. METHODS: An eight-session psychoeducational group that
      provided psychosocial support and information aimed at assisting in the
      bereavement process was initiated at an outpatient cancer center. It was led by a
      family therapist who was a member of a psychosocial services team. Family members
      and friends of recently deceased patients were invited to participate by letter
      and phone call. RESULTS: Seven people participated in at least one group session.
      Participants were asked to complete a face-valid follow-up questionnaire three
      months after completion of the group. CONCLUSIONS: Group members found the group
      experience beneficial, especially regarding the opportunity to talk with others
      who had experienced similar losses, learning about the reactions one would expect
      in the grieving process, and developing new strategies to deal with the grief
      associated with the loss.

PMID- 8989640
TI  - Is the failing heart an energy-starved organ?

PMID- 8989642
TI  - Expression of adenylyl cyclase and G-protein beta subunit in end-stage human
      heart failure.
AB  - BACKGROUND: One of the abnormalities in end-stage human heart failure is
      desensitization of the beta-adrenergic signaling pathway, resulting in decreased
      adenylyl cyclase activity and cyclic adenosine 3',5'-monophosphate formation.
      This process includes changes in expression of receptors and G-protein alpha
      subunits. It was hypothesized that changes in the gene expression of G-protein
      beta subunits (Gbeta) and of adenylyl cyclase itself may contribute to the
      attenuation of activation of adenylyl cyclase. METHODS AND RESULTS: The
      hypothesis was tested by determining messenger RNA steady-state levels (Northern
      and slot-blot analyses) of adenylyl cyclase type V (a major isoform in adult
      myocardium) and Gbeta in the left ventricles of patients with terminal heart
      failure because of idiopathic dilated cardiomyopathy (n = 10) or ischemic heart
      disease (n = 7) and in the left ventricles of nonfailing donors (n = 5). Adenylyl
      cyclase type V messenger RNA was elevated by 85 +/- 25% in dilated cardiomyopathy
      and by 113 +/- 35% in ischemic heart disease (P < .05 vs nonfailing hearts). In
      contrast, Gbeta messenger RNA was unchanged in cardiomyopathy (3.48 +/- 0.18
      pg/microgram total RNA vs nonfailing hearts 3.99 +/- 0.46) and decreased in
      ischemic heart disease (2.43 +/- 0.26, P < .01). CONCLUSION: The data indicate
      that gene expression of the major cardiac isoform of adenylyl cyclase (type V)
      seems increased in human end-stage heart failure. Therefore, attenuated adenylyl
      cyclase activity in this condition may not be the result of adenylyl cyclase
      messenger RNA downregulation. Similarly, the unchanged or decreased expression of
      Gbeta argues against changes in Gbeta contributing to this process.

PMID- 8989641
TI  - Hemodynamic predictors of early intolerance and long-term effects of propranolol
      in dilated cardiomyopathy.
AB  - BACKGROUND: Fifty-six patients with dilated cardiomyopathy (DCM) (aged 14-68
      years) and background therapy of angiotensin-converting enzyme inhibitors,
      diuretics, and digoxin were given an initial challenge of propranolol in
      gradually increasing doses. These patients were studied noninvasively and
      hemodynamically and subjected to right ventricle biopsy. METHODS AND RESULTS:
      Forty-four patients tolerated propranolol and received the drug for 6 months; 12
      patients deteriorated after starting the drug with worsening of congestive heart
      failure and/or hypotension. The patients who did not tolerate propranolol had
      higher left ventricular end-diastolic dimension (73 +/- 8 vs 66 +/- 8 mm, P <
      .05), and severe mitral regurgitation was more common. Hemodynamically these
      patients had higher heart rate, right ventricular end-diastolic pressure, mean
      pulmonary artery pressure, mean pulmonary artery wedge pressure, and left
      ventricular end-diastolic pressure (102 +/- 16 vs 89 +/- 12 beats/min, 15 +/- 7
      vs 9 +/- 4, 39 +/- 16 vs 31 +/- 12, 28 +/- 8 vs 21 +/- 8, 28 +/- 8 vs 22 +/- 8
      mmHg, respectively, P < .01). These patients had a significantly lower cardiac
      index (1.9 +/- 0.6 vs 2.5 +/- 0.6 L/min/m2, P < .01). Forty patients completed 6
      months follow-up evaluation and were further subjected to repeat noninvasive and
      hemodynamic study. There was a significant improvement in New York Heart
      Association class, cardiothoracic ratio, and left ventricular end-diastolic
      dimension (68% vs 62%, 66 +/- 8 vs 62 +/- 7 mm, respectively, P < .01), while the
      ejection fraction (EF) rose from 23 to 35% (P < .001). Hemodynamically, there was
      a significant decrease in heart rate, right ventricular end-diastolic pressure,
      mean pulmonary artery pressure, mean pulmonary artery wedge pressure, and left
      ventricular end-diastolic pressure (91 +/- 14 vs 71 +/- 5 beats/min, 9 +/- 4 vs 5
      +/- 3, 32 +/- 11 vs 22 +/- 7, 25 +/- 9 vs 17 +/- 8, 21 +/- 7 vs 14 +/- 4 mmHg, P
      < .05). The cardiac index rose from 2.3 +/- 0.6 to 3.2 +/- 0.7 L/min/m2 (P <
      .01). CONCLUSIONS: Propranolol in dilated cardiomyopathy is associated with
      significant intolerance. Those who tolerate propranolol seem to have long-term
      beneficial effects. This study is limited as it is uncontrolled and
      nonrandomized.

PMID- 8989643
TI  - Decreased inotropic but relatively preserved relaxation response to cyclic
      adenosine monophosphate-dependent agents in myopathic human myocardium.
AB  - BACKGROUND: Increased intracellular concentrations of cyclic adenosine
      monophosphate (AMP) stimulate a positive inotropic and lusitropic response in
      healthy myocardial tissue. Heart failure results in an attenuated inotropic
      response to cyclic AMP-dependent agents. This study compares the inotropic versus
      relaxation response to cyclic AMP-dependent and cyclic AMP-independent agents in
      myocardium from patients with end-stage heart failure and control patients
      without heart failure. METHODS AND RESULTS: Fifty-four control and 59 myopathic
      human ventricular trabeculae, 1 mm or less in diameter were placed in physiologic
      saline, 2.5 mM Ca2+, and stretched to the length at which maximal isometric force
      developed at 30 degrees C, 0.33 Hz. Dose-response curves plotted as percentage
      change from baseline versus concentration of drug were determined for
      acetylstrophanthidin, isoproterenol, isobutylmethylxanthine, and milrinone.
      Acetylstrophanthidin, a cyclic AMP-independent agent, showed similar increases in
      peak tension relative to baseline over the entire dose range tested for both
      control and myopathic heart muscle; its effect on relaxation of control and
      failing cardiac muscle was equivalent over the dose range tested. In contrast,
      the inotropic actions of the cyclic AMP-dependent agents, isoproterenol and the
      phosphodiesterase inhibitors, were significantly decreased in myopathic muscle
      compared with control muscle, but effects on relaxation in the control and
      myopathic groups remained relatively preserved. CONCLUSIONS: A relatively
      preserved relaxant effect is associated with the cyclic AMP-dependent agents,
      despite significant diminution of their inotropic effects. Thus, in advanced
      heart failure, patients may continue to benefit from the lusitropic effects of
      the cyclic AMP-dependent agents, even when the inotropic effects of these agents
      are severely attenuated.

PMID- 8989644
TI  - Long-term 1-carnitine treatment prolongs the survival in rats with adriamycin
      induced heart failure.
AB  - BACKGROUND: The most serious consequence of heart failure is the shortened life
      expectancy, which may be associated with myocardial energy starvation. METHODS
      AND RESULTS: Eight-week-old male Sprague-Dawley rats received 6 intraperitoneal
      injections of adriamycin (group A: total dose; 15 mg/kg body weight) or vehicle
      (group C) over 2 weeks. Rats then received either 272 mg/kg daily of oral 1
      carnitine (A-LC and C-LC groups) or saline (A-S and C-S groups) for 6 weeks. The
      cumulative mortality rate in the A-LC group was significantly lower than in the A
      S group (13 vs 42%, P = .028). Myocardial levels of high-energy phosphate
      compounds (ATP and creatine phosphate) and fatty acid metabolites (free
      carnitine, short-chain and long-chain acylcarnitine, and long-chain acyl CoA) in
      the left ventricle were measured the day after the last dose of drug or vehicle
      was administered. ATP was decreased by 73%, creatine phosphate by 61%, free
      carnitine by 52%, short-chain acylcarnitine by 48%, and long-chain acylcarnitine
      by 56% in the A-S group compared to the C-S group. Long-chain CoA was increased
      by 168% in the A-S group. Levels of myocardial high-energy phosphate compounds
      and fatty acid metabolites were near normal in adriamycin- and 1-carnitine
      treated rats. CONCLUSIONS: Preservation of the myocardial level of carnitine by 1
      carnitine treatment prolonged survival of rats with adriamycin-induced failure by
      improving the myocardial metabolism of fatty acids.

PMID- 8989645
TI  - Effects of long-term treatment with trandolapril on augmented vasoconstriction in
      rats with chronic heart failure.
AB  - BACKGROUND: Despite the clinical relevance of angiotensin I-converting enzyme
      (ACE) inhibitors, their effects on impaired vascular function in patients and
      animals with chronic heart failure (CHF) have not been fully understood. This
      study was undertaken to determine whether long-term treatment with an ACE
      inhibitor improved the altered contractile properties of vessels from rats with
      CHF. METHODS AND RESULTS: Twelve weeks after coronary artery ligation, the rats
      were sacrificed and the isometric tension development of thoracic aorta,
      pulmonary artery, and mesenteric artery with and without endothelium was
      examined. Contractile responses to norepinephrine and prostaglandin F2 alpha were
      augmented in endothelium-intact, but not in endothelium-denuded, thoracic aorta
      and pulmonary artery segments of the rat with CHF. The contractile response to
      angiotensin II was augmented in endothelium-denuded mesenteric artery segments of
      the rat with CHF, which was attenuated by indomethacin or diclofenac sodium but
      not by bunazosin. Trandolapril (3 mg/kg/d) was administered orally from the 2nd
      to 12th week after the operation. Treatment with trandolapril reversed the
      augmented contractile response of the rat with CHF to norepinephrine,
      prostaglandin F2 alpha, and angiotensin II almost to the levels in the sham
      operated rat. CONCLUSIONS: The results demonstrate that an ACE inhibitor is
      capable of reversing altered vascular function in the rat with CHF, suggesting
      that vascular beds are possible sites of action for ACE inhibitors in the therapy
      for CHF.

PMID- 8989646
TI  - Direct effects of chronic beta-adrenergic receptor blockade on left ventricular
      and myocyte function in a model of tachycardia-induced congestive heart failure.
AB  - BACKGROUND: Chronic beta-receptor blockade (beta-blockade) has been reported to
      improve symptoms and increase survival in patients with congestive heart failure
      (CHF); however, whether the mechanisms for the effects of beta-blockade in CHF
      are due to modulating chronotropy, inotropy, or both remains unknown. To address
      this issue, left ventricular function and isolated myocyte function were examined
      with chronic beta-blockade in a rapid pacing model of CHF, thereby eliminating
      potential chronotropic effects of beta-blockade. METHODS AND RESULTS: Pigs were
      randomly assigned to three groups of six pigs each: supraventricular tachycardia
      (SVT): 3 weeks of atrial pacing at 240 beats/min; SVT/beta-blockade: 3 weeks of
      rapid pacing and beta-blockade (25 mg atenolol twice daily on days 14-21 of
      pacing); control group, sham control animals. This dosage schedule for beta
      blockade was chosen because catecholamines are persistently elevated by day 14 in
      this model of CHF. Left ventricular fractional shortening and end-diastolic
      dimension were measured by echocardiography in the conscious state with a resting
      ambient heart rate. Isolated left ventricular myocyte function was examined using
      high-speed videomicroscopy. Supraventricular tachycardia caused left ventricular
      dilation (5.4 +/- 0.1 vs 3.5 +/- 0.1 cm) and reduced fractional shortening (12 +/
      1% vs 35 +/- 1%) compared with control animals (P < .05). The SVT/beta-blockade
      group showed no significant effects on left ventricular size or function compared
      with the SVT group, but their ambient resting heart rate was reduced by 20%
      relative to the SVT group (P < .05). Myocyte shortening was reduced in the SVT
      group (2.2 +/- 0.1% vs 4.5 +/- 0.1%, P < .05) compared with the control group and
      increased from SVT-only values with beta-blockade (2.7 +/- 0.1%, P < .05).
      Similarly, myocyte shortening velocity was similarly reduced in the SVT and
      SVT/beta-blockade groups (31 +/- 1 and 32 +/- 1 microns/s) compared with the
      control group (51 +/- 1 microns/s, P < .05). With SVT/beta-blockade myocyte
      contraction duration was prolonged (525 +/- 5 ms) compared with SVT-only or
      control values (469 +/- 9 and 473 +/- 4 ms, P < .05). Thus, institution of beta-1
      selective blockade during the development of SVT-induced CHF altered the temporal
      characteristics of the myocyte contraction process, which resulted in improved
      myocyte shortening. CONCLUSIONS: In a model of CHF due to the maintenance of a
      chronically elevated heart rate, institution of beta-1-selective blockade during
      the progression of the CHF process minimally affected left ventricular size and
      function. At the level of the myocyte, chronic beta-1-receptor blockade prolonged
      the contraction interval and thereby increased myocyte shortening. These unique
      results suggest that a contributory mechanism for the effects of beta-blockade in
      the setting of CHF is chronotropic modulation.

PMID- 8989647
TI  - Molecular basis of depression of Ca2+ sensitivity of tension by acid pH in
      cardiac muscles of the mouse and the rat.
AB  - BACKGROUND: Acid pH decreases the Ca2+ sensitivity of myocardial tension
      generation, and recent studies have suggested that regulatory proteins are
      involved. The current study defines the molecular basis of this effect on
      troponin C (TnC) and troponin I (TnI) and also addresses previous differences
      between the rat and mouse. METHODS AND RESULTS: Endogenous cardiac TnC and
      cardiac TnI in isolated trabeculae from mice and rats were exchanged with their
      fast-twitch skeletal muscle counterparts. A cardiac-skeletal TnC chimera was used
      to define the target region for proton action on cardiac TnC. Finally, cardiac
      TnC and skeletal TnC were genetically modified by insertion of a tryptophan for
      phenylalanine-26 to probe the pH effects with fluorescence spectroscopy. The pH
      6.2 effects on Ca2+ sensitivity of force development in mouse and rat
      cardiotrabeculae are largely accounted for by the proton influences on TnC (23%)
      and TnI (53%). In cardiac TnC, residues 1 to 41 provide the target region.
      Comparison of the Ca(2+)-induced fluorescence in isolated cardiac TnC and
      skeletal TnC also indicated a greater pH effect in the cardiac isoform.
      CONCLUSIONS: The studies provide firm evidence that both TnC and TnI moieties are
      involved in the mechanism of acidosis causing reduction in the Ca sensitivity of
      force development in the myocardium. The findings rule out the possibility of
      interspecies variations in the underlying mechanisms. The genetically designed
      TnCs and a chimera demonstrate that the observed TnC-mediated difference in the
      pH effects on Ca2+ sensitivity of tension between cardiac and skeletal muscles is
      preserved in these isolated proteins. The N-terminal amino acid residues 1 to 41
      in cardiac TnC are established as the pH sensor of this protein in the mouse as
      in the rat.

PMID- 8989648
TI  - Distribution of neurons projecting to the superior colliculus correlates with
      thick cytochrome oxidase stripes in macaque visual area V2.
AB  - In visual area V2 of macaque monkeys, cytochrome oxidase (CO) histochemistry
      reveals a pattern of alternating densely labeled thick and thin stripe
      compartments and lightly labeled interstripe compartments. This modular
      organization has been associated with functionally separate pathways in the
      visual system. We examined this idea further by comparing the pattern of CO
      stripes with the distribution of neurons in V2 that project to the superior
      colliculus. Visually evoked activity in the superior colliculus is known to be
      greatly reduced by blocking magnocellular but not parvocellular layers of the
      lateral geniculate nucleus (LGN). From previous evidence that V2 thick stripes
      are closely associated with the magnocellular LGN pathway, we predicted that a
      significant proportion of V2 neurons projecting to the superior colliculus would
      reside in the thick stripes. To test this prediction, the tangential distribution
      of retrogradely labeled corticotectal cells in V2 was compared with the pattern
      of CO stripes. We found that neurons projecting to the superior colliculus
      accumulated preferentially into band-like clusters that were in alignment with
      alternate CO dense stripes. These stripes were identified as thick stripes on the
      basis of their physical appearance and/or by their affinity to the monoclonal
      antibody Cat-301. A significantly smaller proportion of labeled cells was
      observed in thin and interstripe compartments. These data provide further
      evidence that the spatial distribution of subcortically projecting neurons can
      correlate with the internal modular organization of visual areas. Moreover, they
      support the notion that CO compartments in V2 are associated with functionally
      different pathways.

PMID- 8989649
TI  - Organ cultures of embryonic rat tongue support tongue and gustatory papilla
      morphogenesis in vitro without intact sensory ganglia.
AB  - Taste buds on the mammalian tongue are confined to the epithelium of three types
      of gustatory papillae: the fungiform, circumvallate, and foliate. The gustatory
      papillae are composed of an epithelium that covers a broad connective tissue
      core, with extensive innervation to taste bud and nongustatory epithelial
      locations. Although the temporal sequence of gustatory papilla development is
      known for several species, factors that regulate initiation, growth, and
      maintenance of the papillae are not understood. We tested the hypothesis that
      sensory innervation is required for the initial formation and early morphogenesis
      of fungiform papillae in a patterned array. An organ culture of the embryonic rat
      tongue was developed to provide an in vitro system for studying mechanisms
      involved in fungiform papilla morphogenesis in patterns on the anterior tongue.
      Tongues were dissected from embryos at 13 days of gestation (E13), a time when
      the tongue has not yet fully formed and gustatory papillae have not yet appeared,
      and at 14 days of gestation (E14), when the tongue is well formed and papillae
      make their initial morphological appearance. Dissected tongues were maintained at
      the gas/liquid interface in standard organ culture dishes, fed with DMEM/F12 plus
      2% B-27 supplement and 1% fetal bovine serum. After 1, 2, 3, or 6 days in
      culture, tongues were processed for scanning electron or light microscopy, or
      immunocytochemistry. Tongues cultured from E13 or E14 underwent extensive
      morphogenesis and growth in vitro. Furthermore, fungiform papillae developed on
      these tongues on a culture day equivalent to E15 in vivo; that is, after 2 days
      for cultures begun at E13 and 1 day for those begun at E14. Because E15 is the
      characteristic time for gustatory papilla formation in the intact embryo, results
      demonstrate that the cultured tongues retain important temporal information
      related to papilla development. In addition, fungiform papillae formed in the
      tongue cultures in the stereotypic pattern of rows. The papillae were large
      structures with epithelial and mesenchymal cell integrity, and an intact
      epithelial basement membrane was indicated with laminin immunoreactivity. The
      cultures demonstrate that gustatory papilla morphogenesis can progress in the
      absence of an intact sensory innervation. To exclude a potential developmental
      role for autonomic ganglion cells that are located in the posterior rat tongue,
      cultures consisting of only the anterior half of E14 tongues were established.
      Fungiform papilla development progressed in half tongues in a manner directly
      comparable to whole tongue cultures. Therefore, robust, reproducible development
      of fungiform papillae in patterns is supported in rat tongue cultures from E13 or
      E14, without inclusion of intact sensory or major, posterior tongue autonomic
      ganglia. This is direct evidence that papillae will form and develop further in
      vitro without sensory ganglion support. The data also provide the first detailed
      account of in vitro development of the entire embryonic tongue.

PMID- 8989650
TI  - Differentiation and morphogenesis in pellet cultures of developing rat retinal
      cells.
AB  - We previously developed a reaggregate cell culture system (pellet cultures) in
      which retinal neuroepithelial cells proliferate and give rise to rod
      photoreceptor cells (rods) in vitro (Watanabe and Raff, 1990, Neuron 4:461-467).
      In the present study, we analyzed cell differentiation and morphogenesis in
      pellet cultures by using both cell-type-specific markers with immunofluorescence
      and electron microscopy. We demonstrated that, in addition to rods, the other
      major retinal cell types, including amacrine cells, bipolar cells, Muller cells,
      and ganglion cells were all present in the pellets, where most were able to
      develop from dividing precursor cells in vitro. The different cell types in the
      pellets became organized into two distinct structures: dark rosettes and pale
      rosettes. The cellular composition of these structures indicated that the dark
      rosettes correspond to the outer nuclear layer and the pale rosettes to the inner
      nuclear layer of the normal retina. Ultrastructural studies have indicated that
      the thin layer of neuronal processes surrounding the dark rosettes correspond to
      the outer plexiform layer, and the central region of the pale rosettes correspond
      to the inner plexiform layer of the normal retina. Other features of normal
      retinal development also occurred in the pellets, including programmed cell death
      and the formation of inner and outer rod cell segments and synapses. Thus, pellet
      cultures provide a convenient way to study different aspects of retinal
      development where one can control the size and the cellular composition of the
      initial reaggregate.

PMID- 8989651
TI  - Xefiltin, a new low molecular weight neuronal intermediate filament protein of
      Xenopus laevis, shares sequence features with goldfish gefiltin and mammalian
      alpha-internexin and differs in expression from XNIF and NF-L.
AB  - The nervous system of the postmetamorphic frog Xenopus laevis, like that of other
      amphibians, shows continued growth and a high capacity for regeneration,
      especially in its visual system. This characteristic has been attributed, in
      part, to the retention in adults of traits that in mammals are limited to
      embryos. In mammals, the progressive maturation of neurons is marked by
      successive changes in neuronal intermediate filament (nIF) subunit composition.
      For example, in mammalian forebrain, newly differentiating neurons first express
      the low molecular weight nIF protein alpha-internexin. As neurons mature, alpha
      internexin expression declines, and expression of the low molecular weight
      neurofilament triplet protein (NF-L) increases. Thus, a systematic examination of
      the expression of low molecular weight nIF proteins in the postmetamorphic frog
      might reveal whether the nIF subunit composition of its neurons more closely
      resembles that of embryonic as opposed to adult mammals. Previously, X. laevis
      has been shown to express both NF-L and XNIF, a novel low molecular weight nIF
      protein that most closely resembles mammalian alpha-internexin. We have now
      discovered a new, low molecular weight nIF protein with even higher homology to
      alpha-internexin. We named this protein xefiltin, because it shared highest
      sequence identity with gefiltin, an alpha-internexin-like nIF protein from the
      goldfish visual system. In situ hybridization with probes to xefiltin, XNIF and
      NF-L showed that transcripts of all three were expressed widely throughout the
      post-metamorphic frog nervous system, but with distinctly different patterns of
      expression. For example, xefiltin was the most abundantly expressed of the three
      in retinal ganglion cells and in neurons of the habenular nucleus and
      telencephalon, whereas XNIF and NF-L were found at higher levels than xefiltin in
      peripheral sensory ganglia and in structures caudal to the mesencephalon. In
      general, the combined distributions of xefiltin and XNIF paralleled the
      distribution of alpha-internexin in mammalian embryos. Thus, we speculate that
      the persistence of alpha-internexin-like nIF proteins in the amphibian nervous
      system may be important for its continued potential for growth and plasticity.

PMID- 8989652
TI  - Ciliary neurotrophic factor receptor alpha-immunoreactivity in the monkey central
      nervous system.
AB  - Ciliary neurotrophic factor (CNTF) sustains the viability and phenotypic
      expression of a variety of neuronal populations in the central nervous system.
      Cranial and spinal motor neurons are particularly sensitive to the trophic
      effects of CNTF, and clinical trials are underway testing the potential
      therapeutic value of this trophic factor in patients with amyotrophic lateral
      sclerosis. Yet, the distribution of the alpha subunit of the receptor for ciliary
      neurotrophic factor (CNTFR alpha), which is essential for the trophic effects of
      CNTF to occur, is unknown in any primate species. Towards this end, the present
      study used a polyclonal antibody directed against CNTFR alpha to evaluate the
      distribution of CNTFR alpha-immunoreactive (-ir) cells within the brain and
      spinal cord of Cebus apella monkeys. CNTFR alpha-ir was found exclusively within
      neurons. In the anterior horn of the spinal cord, virtually all motor neurons
      were darkly immunoreactive for CNTFR alpha. A similar pattern of CNTFR alpha-ir
      was seen within all cranial motor nuclei with general somatic efferent function
      (III, IV, motor V, VI, VII, and XII cranial nerves). CNTFR alpha-ir was also seen
      in other regions involved with motor function including the Purkinje cells of the
      cerebellum, the substantia nigra pars compacta, red nucleus, dorsal motor nucleus
      of X cranial nerve, and giant neurons of sensory motor neocortex. A few CNTFR
      alpha-ir neurons were seen within the globus pallidus with concomitant terminal
      like staining within the subthalamic nucleus. Autonomic regions such as the
      mesencephalic nucleus of the trigeminal nerve and the interomedial lateral cell
      column of the thoracic spinal cord also contained CNTFR alpha-ir neurons.
      Finally, the hippocampus displayed dense CNTFR alpha-ir within the pyramidal cell
      layer of the hippocampal formation and the granule cell layer of the dentate
      gyrus. The dense expression of this CNTFR alpha protein within regions subserving
      motor, autonomic, and sensory functions suggests that CNTFR alpha supports many
      central nervous system regions with diverse functions.

PMID- 8989653
TI  - Noradrenergic input to nociceptive modulatory neurons in the rat rostral
      ventromedial medulla.
AB  - Within the rostral ventromedial medulla (RVM), there are two classes of putative
      pain modulation neurons: ON cells and OFF cells, which respectively burst or
      pause prior to withdrawal reflexes elicited by noxious stimulation. Alpha
      adrenergic agonists injected into the RVM produce changes in the latency of
      spinal nocifensive reflexes and, when iontophoretically applied, alter the firing
      of RVM ON but not OFF cells. To provide further information about the
      contribution of norepinephrine to RVM neuron function, we analyzed the
      distribution of tyrosine hydroxylase immunoreactive (TH-ir) appositions upon RVM
      ON and OFF cells. In the lightly anesthetized rat, seven ON and five OFF cells
      were identified by changes in their discharge rate in relation to nociceptive
      withdrawal reflexes and were labeled by intracellular injection of neurobiotin.
      Sections containing labeled cells were visualized by using avidin conjugated to a
      Texas Red fluorophore. Tissue with labeled cells was subsequently processed for
      TH-ir by using a Bodipy fluorophore conjugated secondary antibody. The
      distribution of the Bodipy-labeled fibers and terminals upon the Texas Red
      labeled neurons was mapped using a confocal laser-scanning microscope. All the
      labeled neurons exhibited close TH-ir appositions. Appositions were of two types:
      swellings and fibers. Although the numbers and density of appositions varied
      among the cells, there were no consistent differences that correlated with
      physiological properties. Thus the overall density of appositions for ON cells
      (29.0 +/- 22.2 x 10(4) microns2) did not differ significantly from that for OFF
      cells (25.4 +/- 22.2 x 10(4) microns2). Tyrosine hydroxylase immunoreactive (TH
      ir) appositions upon ON and OFF cells varied with their location along the dorso
      ventral axis with more ventral neurons having a greater density of TH-ir swelling
      type appositions. In a separate study, TH-ir and dopamine-beta-hydroxylase-like
      immunoreactivity (DBH-ir) were mapped in the same sections by using confocal
      microscopy. Nearly 97% of the TH-ir profiles co-localized with DBH-ir. These
      observations provide evidence that both ON and OFF cells in the RVM are targeted
      by noradrenergic inputs.

PMID- 8989654
TI  - Projections of the dorsomedial nucleus of the intercollicular complex (DM) in
      relation to respiratory-vocal nuclei in the brainstem of pigeon (Columba livia)
      and zebra finch (Taeniopygia guttata).
AB  - Injections of neuronal tracers were made into the dorsomedial nucleus of the
      intercollicular complex (DM) of pigeons and zebra finches in order to investigate
      the projections of this nucleus which has long been implicated in respiratory
      vocal control. Despite the fact that pigeons are nonsongbirds and zebra finches
      are songbirds, the projections were very similar in both species. Most descended
      throughout the brainstem, taking ventral and dorsal trajectories, which merged in
      the medulla. Those descending ventrally terminated upon the ventrolateral
      parabrachial nucleus (PBvl), the nucleus infraolivaris superior, a nucleus of the
      rostral ventrolateral medulla (RVL), and the nucleus retroambigualis (RAm). Those
      taking a dorsal trajectory via the occipitomesencephalic tract terminated in the
      tracheosyringeal part of the hypoglossal nucleus (XIIts), the suprahypoglossal
      region, and nucleus retroambigualis. There were also substantial projections
      throughout an arc extending between XIIts and RVL rostrally, and XIIts and RAm
      caudally. Neurons throughout this arc, which include inspiratory premotor neurons
      at levels straddling the obex and expiratory premotor neurons more caudally (in
      RAm), were retrogradely labeled from spinal injections. The DM projections were
      predominantly ipsilateral, but there were distinct contralateral projections to
      all the homologous nuclei in both species. All but the projections to PBvl and
      XIIts were reciprocal. In summary, the projections of DM suggest that it is able
      to influence all the key motor and premotor nuclei involved in patterned
      respiratory-vocal activity.

PMID- 8989655
TI  - Fates of the earliest generated cells in the developing murine neocortex.
AB  - In mammalian species studied to date, the first-born neocortical cells normally
      form two layers, one above and one below the cortical plate, called the marginal
      zone (future layer 1) and the subplate. In primates and carnivores, many of these
      first-born cells die early in postnatal life. Whether this also occurs in rodents
      is highly controversial. In this study, we injected pregnant mice with
      bromodeoxyuridine on embryonic days (E) 11-14 to label the earliest generated
      neocortical cells, and examined their fates between birth and postnatal day 21.
      At birth, most cells born on embryonic day 11 were below the cortical plate, and
      a smaller proportion were above it. Very few of these cells remained by postnatal
      day 3 and there were none at any depth in the neocortex at older ages. At birth,
      the largest proportion of cells born on embryonic days 12 and 13 were in the
      subplate and smaller proportions were in the cortical plate and marginal zone. At
      older ages, almost all of these cells had disappeared from the marginal zone and
      from below the cortical plate, although some were retained in the cortical plate.
      The density of the remaining E12- and E13-born cells decreased more than could be
      explained by neocortical expansion alone. As a control, we studied cells born on
      embryonic day 14. These cells were restricted to the cortical plate at birth. By
      postnatal day 21, their density had decreased by an amount that could be
      explained by neocortical expansion alone. We conclude that, as in other species,
      many of the earliest generated cells of the murine neocortex die.

PMID- 8989656
TI  - Compound synapses within the GABAergic innervation of the auditory inner hair
      cells in the adolescent mouse.
AB  - Ultrastructural investigation of the gamma-aminobutyric acid (GABA) component of
      the inner spiral bundle in adolescent mice revealed a pathway of glutamic acid
      decarboxylase (GAD)-positive and -negative fibers and vesiculated endings that
      contact inner hair cells and their afferents through a complex of axosomatic and
      axodendritic synapses. Ultrastructural details were investigated by using
      conventional electron microscopy. Several synaptic arrangements were observed:
      Main axosomatic synapses form between vesiculated endings and individual or
      adjoining inner hair cells (interreceptor synapses). Spinous synapses form on
      long, spinelike processes that protrude from inner hair cells to reach distant
      efferent endings. The efferent endings associate with inner hair cells and their
      synaptic afferents through compound synapses-serial, "converging," and triadic
      otherwise characteristic of sensory relay nuclei. Serial synapses form by the
      sequential presynaptic alignment of the efferent-->receptor-->afferent
      components. Converging synapses result from the simultaneous apposition of a
      receptor ribbon synapse and a presynaptic efferent terminal on a recipient
      afferent dendrite. Triadic synapses comprise a vesiculated efferent ending in
      contact with an inner hair cell and with its synaptic afferent. Additionally,
      efferent endings may form simple axodendritic and axoaxonal synapses with GAD
      negative vesiculated endings. The combination of different synaptic arrangements
      leads to short chains of compound synapses. It is assumed that these synaptic
      patterns seen in the adolescent mouse represent adult synaptology. The patterns
      of synaptic connectivity suggest an integrative role for the GABA/GAD lateral
      efferent system, and imply its involvement in the pre- and postsynaptic
      modulation of auditory signals.

PMID- 8989657
TI  - Cellular inflammatory response after spinal cord injury in Sprague-Dawley and
      Lewis rats.
AB  - The distribution of microglia, macrophages, T-lymphocytes, and astrocytes was
      characterized throughout a spinal contusion lesion in Sprague-Dawley and Lewis
      rats by using immunohistochemistry. The morphology, spatial localization, and
      activation state of these inflammatory cells were described both qualitatively
      and quantitatively at 12 hours, 3, 7, 14, and 28 days after injury. By use of
      OX42 and ED1 antibodies, peak microglial activation was observed within the
      lesion epicenter of both rat strains between three and seven days post-injury
      preceding the bulk of monocyte influx and macrophage activation (seven days).
      Rostral and caudal to the injury site, microglial activation plateaued between
      two and four weeks post-injury in the dorsal and lateral funiculi as indicated by
      morphological transformation and the de-novo expression of major
      histocompatibility class II (MHC II) molecules. Similar to the timing of
      microglial reactions, T-lymphocytes maximally infiltrated the lesion epicenter
      between three and seven days post-injury. Reactive astrocytes, while present in
      the acute lesion, were more prominent at later survival times (7-28 days). These
      cells were interspersed with activated microglia but appeared to surround and
      enclose tissue sites occupied by reactive microglia and phagocytic macrophages.
      Thus, trauma-induced central nervous system (CNS) inflammation, regardless of
      strain, occurs rapidly at the site of injury and involves the activation of
      resident and recruited immune cells. In regions rostral or caudal to the
      epicenter, prolonged activation of inflammatory cells occurs preferentially in
      white matter and primarily consists of activated microglia and astrocytes.
      Differences were observed in the magnitude and duration of macrophage activation
      between Sprague-Dawley (SD) and Lewis (LEW) rats throughout the lesion. Increased
      expression of complement type 3 receptors (OX42) and macrophage-activation
      antigens (ED1) persisted for longer times in LEW rats while expression of MHC
      class II molecules was attenuated in LEW compared to SD rats at all times
      examined. Variations in the onset and duration of T-lymphocyte infiltration also
      were observed between strains with twice as many T-cells present in the lesion
      epicenter of Lewis rats by 3 days post-injury. These strain-specific findings
      potentially represent differences in corticosteroid regulation of immunity and
      may help predict a range of functional neurologic consequences affected by
      neuroimmune interactions.

PMID- 8989658
TI  - Selective blockade of the delayed rectifier potassium current by tacrine in
      Drosophila.
AB  - Tetrahydroaminoacridine (tacrine) is an anticholinesterase agent used in the
      treatment of Alzheimer's disease. Its effectiveness against dementia is
      attributed to its inhibition of acetylcholine breakdown in the synaptic cleft.
      Tacrine has also been shown to block ionic currents, including many types of
      potassium (K+) currents, calcium currents, and sodium currents. However, the
      physiologic significance of this blockade, especially with respect to its
      effectiveness against Alzheimer's disease, is not clear because of relatively
      high (several hundred micromolar to millimolar) concentrations of tacrine
      employed in many studies of channel blockade, and because it blocks several types
      of currents. A complete mutational and pharmacologic resolution of ionic currents
      in the larval muscles of Drosophila allowed us to examine the selectivity of
      tacrine's effects at very low concentrations. At concentrations as low as 10
      microM, tacrine selectively blocked the delayed rectifier K+ current without
      affecting the three other K+ currents or the calcium channel current in these
      cells. It also increased the duration of the action potentials significantly. An
      interesting aspect of tacrine's selectivity is that the current blocked by it is
      the quinidine-sensitive delayed rectifier K+ current rather than the 4
      aminopyridine (4-AP)-sensitive transient K+ current. This is in contrast to the
      generally emphasized structural relationship between tacrine and 4-AP. Since
      tacrine is structurally related to quinidine as well, these observations suggest
      a structural basis for the selectivity of tacrine, 4-AP, and quinidine for
      specific K+ channels. Furthermore, the data are consistent with the possibility
      of increased neurotransmitter release, due to prolonged presynaptic action
      potentials, acting synergistically with the anticholinesterase activity of
      tacrine to increase its therapeutic effectiveness.

PMID- 8989659
TI  - Resting potential of rat cerebellar granule cells during early maturation in
      vitro.
AB  - The survival of rat cerebellar granule cells maintained in vitro is enhanced by a
      KCl-enriched medium. This effect is classically interpreted as resulting from a
      higher cytosolic calcium concentration. This implies the presence of voltage
      dependent Ca2+ channels and a membrane potential that can respond to changes in
      external K+. Since previous studies cast a doubt on these two conditions, we
      reinvestigated the resting membrane potential and Ca2+ influxes in rat cerebellar
      granule neurones during the first week in vitro using a fluorescence imaging
      approach. Membrane potential was assessed with the fluorescent dye bis-oxonol,
      and intracellular free calcium with Fura-2. Resting potential was shown to
      progressively decrease from -40 mV at the first day in vitro to -60 mV at day 7.
      At all times in culture, as early as day 0, cells were depolarized when external
      KCl concentration was increased from 5 to 30 mM. This depolarization resulted in
      an increased cytosolic calcium concentration due to Ca2+ influx through L-type
      and N-type voltage-activated Ca2+ channels, functional at day 0. Gross
      estimations of the permeabilities of Na+ and Cl- were obtained at various times
      in culture by measuring the changes in resting potential brought about by a
      reduction of their external concentration. A progressive increase of the relative
      permeability to K+ ions seems to underlie the evolution of the resting potential
      with time.

PMID- 8989660
TI  - Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor for
      sensory neurons: comparison with the effects of the neurotrophins.
AB  - We compared the effects of glial cell line-derived neurotrophic factor (GDNF) on
      dorsal root ganglion (DRG) sensory neurons to that of nerve growth factor (NGF),
      brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3). All of these
      factors were retrogradely transported to subpopulations of sensory neuron cell
      bodies in the L4/ L5 DRG of neonatal rats. The size distribution of 125I-GDNF
      labeled neurons was variable and consisted of both small and large DRG neurons
      (mean of 506.60 microns2). 125I-NGF was preferentially taken up by small neurons
      with a mean cross-sectional area of 383.03 microns2. Iodinated BDNF and NT-3 were
      transported by medium to large neurons with mean sizes of 501.48 and 529.27
      microns2, respectively. A neonatal, sciatic nerve axotomy-induced cell death
      model was used to determine whether any of these factors could influence DRG
      neuron survival in vivo. GDNF and NGF rescued nearly 100% of the sensory neurons.
      BDNF and NT-3 did not promote any detectable level of neuronal survival despite
      the fact that they underwent retrograde transport. We examined the in vitro
      survival-promoting ability of these factors on neonatal DRG neuronal cultures
      derived from neonatal rats. GDNF, NGF, and NT-3 were effective in vitro, while
      BDNF was not. The range of effects seen in the models described here underscores
      the importance of testing neuronal responsiveness in more than one model. The
      biological responsiveness of DRG neurons to GDNF in multiple models suggests that
      this factor may play a role in the development and maintenance of sensory
      neurons.

PMID- 8989661
TI  - Activin receptor mRNA expression by neurons of the avian ciliary ganglion.
AB  - Previous studies have suggested that activin may serve as a neurodifferentiation
      factor regulating somatostatin expression in neurons of the avian ciliary
      ganglion (CG). As one aspect of examining the role of activin in CG development,
      we inquired whether any of the known activin receptors are expressed by
      developing CG neurons in vivo. In addition, we examined whether activin A mRNA is
      expressed in the choroid layer and iris of the chicken eye. Oligonucleotide
      primers were designed for the chicken activin receptor type IIA (cActR-IIA), type
      IIB (cActR-IIB), and activin A. In reverse-transcription-polymerase chain
      reaction (rtPCR), an appropriately sized product was amplified from CG cDNA using
      primers to the cActR-IIA but not the cActR-IIB. Sequencing confirmed the identity
      of the PCR product as a fragment of the cActR-IIA. It thus appears that mRNA for
      the type IIA but not the type IIB activin receptor is expressed in the chicken
      CG. An antisense strand digoxigenin-labeled riboprobe complimentary to a 358-bp
      portion of the cActR-IIA kinase region hybridized to cells within cryostat
      sections of embryonic CG. From E6.5-E18, hybridization of this probe appears to
      be specific for cells with a neuronal morphology. Using rtPCR with activin A
      specific primers we detected activin mRNA in the choroid layer of E14 and E19
      eyes, and from the iris at E14. Our results are consistent with a role for
      activin as a neurodifferentiation factor in vivo, and imply that within the CG,
      the cActR-IIA is specifically expressed by neurons, and that activin A is
      expressed in the targets of these neurons.

PMID- 8989662
TI  - Xenopus Pax-6 and retinal development.
AB  - We have cloned a homolog of Pax-6 in Xenopus laevis. Its deduced amino acid
      sequence has a 95% overall identity with Pax-6 homologs in other vertebrates. It
      is expressed early in development in cells fated to form the eye and parts of the
      forebrain, hindbrain, and spinal cord. It has two phases of expression in the
      eye. In the early phase, from stage 12.5 to stage 33/34, Xenopus Pax-6 is
      expressed throughout the developing retina. In the late phase, after stage 33/34,
      it is excluded from mature cells in the outer half of the retina and from cells
      in the ciliary marginal zone, remaining only in amacrine and ganglion cells.
      Misexpression of Pax-6 early in development results in axial defects, but no
      specific eye phenotype is observed. Targeted misexpression in the retina at later
      stages does not result in any significant bias toward formation of amacrine or
      ganglion cells or away from photoreceptors. Ectopic expression of the proneural
      gene NeuroD alters the pattern of Pax-6, substantially reducing its expression in
      the eye field and later reducing or eliminating the eye itself. Our results show
      that Pax-6 expression appears to be necessary, but not sufficient, for eye
      formation in Xenopus.

PMID- 8989663
TI  - Capacitative Ca2+ influx in the neural retina of chick embryo.
AB  - Depletion of intracellular Ca2+ stores induces a capacitative Ca2+ influx in non
      neural cells. It has been unknown whether the capacitative Ca2+ influx occurs in
      the cells of nervous systems. We found the capacitative Ca2+ influx in the neural
      retina of early embryonic chick with Fura-2 fluorescence measurements. A Ca(2+)
      free medium containing thapsigargin (500 nM), an inhibitor of Ca(2+)-ATPase of
      intracellular Ca2+ stores, was applied to the neural retina of embryonic day 3
      (E3) chick. A rise in intracellular Ca2+ concentration was evoked after the
      reintroduction of extracellular Ca2+, and this Ca2+ rise was suppressed by Zn2+
      (1 mM) and Ni2+ (5 mM). The developmental changes in the Ca2+ rise induced by
      thapsigargin (250 nM) were studied from E3 to E13. The thapsigargin-induced Ca2+
      rise was largest at E3, declined rapidly toward E6, and then decreased gradually
      until E13, when the Ca2+ rise almost disappeared. This developmental profile
      correlated with the decline in the mitotic activities of the retinal cells
      studied by Prada et al. The fluorescence imaging with the vertical slice of the
      E9 retina showed that the site at which the thapsigargin-induced Ca2+ rise was
      largest was the most outer layer of the retina, where proliferating cells are
      located. This spatial distribution and the above developmental profile may
      suggest that the capacitative Ca2+ influx occurs at the early period of
      neurogenesis when the cells have mitotic activities.

PMID- 8989664
TI  - Neuronal-type acetylcholine receptors and regulation of alpha 7 gene expression
      in vertebrate skeletal muscle.
AB  - Several neuronal nicotinic acetylcholine receptor (AChR) genes are expressed in
      chick skeletal muscle during development. One of the most abundantly expressed is
      alpha 7, which produces a protein capable of binding alpha-bungarotoxin and is
      physically distinct from muscle AChRs containing the alpha 1 gene product. We
      show here that the alpha 7-containing species in muscle is indistinguishable
      pharmacologically from alpha 7-containing AChRs in neurons. In addition,
      immunologic analysis with subunit-specific muscle antibodies shows that the alpha
      7-containing species in muscle lacks the beta 1 and delta muscle AChR gene
      products as it does the alpha 1. RNase protection experiments measuring alpha 7
      mRNA levels indicate that the alpha 1 and alpha 7 genes may, in part, be subject
      to similar kinds of regulation in the tissue. Surgical denervation of leg muscle
      in newly hatched chicks caused a small and transient increase in alpha 7 mRNA
      after 8 days, while alpha 1 transcripts underwent a large and sustained increase
      in number. Similarly, treating myotube cultures with tetrodotoxin caused a modest
      increase in alpha 7 transcript levels and a large increase in alpha 1. Calcitonin
      gene-related peptide (CGRP) increased both kinds of transcripts in myotube
      cultures equally as did treatment with 8-bromo-cyclic AMP; CGRP is thought to
      work via a cyclic AMP-dependent pathway in muscle. In at least one respect,
      however, alpha 7 expression in muscle differs qualitatively from that of alpha 1:
      AChR-inducing activity (ARIA) increased alpha 1 mRNA levels in culture while
      slightly depressing alpha 7 mRNA levels. The regulatory pattern of alpha 7
      expression in muscle may combine features of both alpha 7 expression in neurons
      and alpha 1 expression in muscle.

PMID- 8989665
TI  - Opposing regulation of ciliary neurotrophic factor receptors on neuroblastoma
      cells by distinct differentiating agents.
AB  - We have used SH-SY5Y neuroblastoma cells as a model for differentiating neurons
      to examine the mechanisms that regulate responses to the neuropoietic cytokine
      ciliary neurotrophic factor (CNTF). Retinoic acid and 12-O-tetradecanoyl-phorbol
      13-acetate (TPA) each induced differentiation of SH-SY5Y cells. Cells treated for
      24 h with retinoic acid (10 microM) showed a threefold increase in 125I-CNTF
      binding sites and were up to five times more sensitive to CNTF than untreated
      cells in stimulating the tyrosine phosphorylation of the transcription factor
      STAT3. TPA (10 nM) induced a transient 42% decrease in 125I-CNTF binding sites
      after 4 h of treatment that recovered to near control levels after 7 h of
      continuous exposure. TPA-treated cells showed a decreased sensitivity to CNTF and
      a sevenfold decrease in levels of STAT3. The retinoic acid-induced increase in
      125I-CNTF binding could be prevented by administration of either cycloheximide or
      actinomycin D, whereas neither agent altered the TPA-induced decrease in 125I
      CNTF binding. In addition, levels of mRNA for both the CNTF receptor alpha and
      gp130 subunits increased twofold as measured by RNase protection after treatment
      with retinoic acid for 30 h. The increase in CNTF receptor alpha subunit mRNA was
      not due to a decrease in its turnover rate, and therefore, was likely due to an
      increase in gene expression. Thus, retinoic acid and TPA regulate CNTF receptors
      on neuroblastoma cells differently, and the results demonstrate the importance of
      transcriptional control of CNTF receptors and also implicate translational and
      post-translational mechanisms in the regulation of cytokine receptors and
      responses on neurons.

PMID- 8989666
TI  - Regulation of voltage- and ligand-gated currents in rat hippocampal progenitor
      cells in vitro.
AB  - Growth medium and substrate regulate the proliferation and differentiation of
      neural progenitor cells in vitro and the expression of cell type-specific
      histochemical markers. An important question is whether neural progenitor cells
      exhibit voltage- and ligand-gated currents, features characteristic of neurons,
      and whether these currents are regulated differentially by growth conditions.
      Another issue of interest is whether passaged progenitor cells, after expansion
      with basic fibroblast growth factor (FGF-2), exhibit the same degree of
      plasticity as their primary counterparts, or whether they are more committed to a
      particular phenotype. In primary cultures of embryonic rat hippocampal progenitor
      cells, growth in proliferative conditions (FGF-2) was associated with low levels
      of sodium, calcium, N-methyl-D-aspartate (NMDA), and kainate currents compared
      with other growth conditions. After multiple passages in the continued presence
      of FGF-2, sodium, calcium, and NMDA, responses declined further; interestingly,
      kainate and gamma-aminobutyric acid (GABA) responses remained substantial.
      Moreover, the expression of functional channels and receptors in primary cultures
      of progenitor cells is up-regulated strongly by growth factors such as BDNF, and
      NT-3, whereas sodium and calcium currents in passaged cultures respond to such
      growth conditions to a lesser extent. Kainate and GABA responses were present to
      a significant extent in passaged cultures, independent of growth condition. We
      conclude that environmental cues regulate different channels and receptors in
      distinct ways in neural progenitor cells.

PMID- 8989667
TI  - Axon-mediated gene transfer of retinal ganglion cells in vivo.
AB  - Modification of the intracellular functions of mature neurons through specific
      gene transfer has many potential applications. Here we present a new methodology
      for the successful transfection of retinal ganglion cells by administration of
      plasmid at the cut end of the optic nerve, or at their intact axon terminals; the
      latter is significantly more efficient. Plasmids contained either the SV40
      promoter linked to the luciferase gene, or the CMV or RSV promoter linked to the
      lacZ gene. Assays for both reporter genes demonstrated significant expression of
      exogenous DNA in the retina for at least 10 days after retrograde transport.
      Duration of expression was extended to 20 days or more (duration of the
      experiment) when plasmid DNA was condensed with poly(L-lysine). beta
      Galactosidase analysis revealed transfection of ganglion cells in high numbers.
      Such an approach for gene delivery to specific subpopulations of neurons might be
      useful in studies of molecular functions in vivo and as an experimental
      therapeutic strategy to extend survival and restore their function.

PMID- 8989668
TI  - Voltage-activated and odor-modulated conductances in olfactory neurons of
      Drosophila melanogaster.
AB  - Voltage-activated currents and odor-modulated conductances were studied in cells
      in semi-intact Drosophila third antennal segments (the main olfactory organ)
      using patch-clamp techniques. All neurons expressed outward currents, and most
      expressed labile fast transient inward currents with kinetics similar to Na+
      currents in other systems. Action potentials were detected as bipolar
      capacitative current transients in cell-attached or loose patches from the soma
      of both odor-sensitive (97%) and insensitive neurons. A mixture of odorants from
      five chemical classes caused an increase (approximately 70%), decrease
      (approximately 10%), or no effect on firing frequency in pharate adult neurons.
      The development of chemosensitivity was examined and odor-induced changes in
      action potential firing frequency were recorded in pupal antennal neurons as
      early as P8, a stage after completion of sensillar development. The character of
      odor-induced responses was more profound and complex later in development; small,
      tonic increases in firing frequency were observed at pupal stages P8 through P11
      (ii), while in older pupae and young adults approximately 25% of the increased
      responses were phasic-tonic. The apical dendrite was the site of odor modulation
      in approximately 90% and 100% of responsive adult and early pupal neurons,
      respectively. Whole-cell recordings revealed that apparent nonselective cation
      and chloride conductances were modulated by a mixture of odorants in separate
      antennal neurons.

PMID- 8989669
TI  - Diversification of the portfolio.

PMID- 8989670
TI  - Quantitative analysis of technetium 99m 2-methoxyisobutyl isonitrile single
      photon emission computed tomography and isosorbide dinitrate infusion in
      assessment of myocardial viability before and after revascularization.
AB  - BACKGROUND: Assessment of viable myocardium in territories of hypoperfused
      myocardium is important for predicting functional recovery after
      revascularization. This study was designed to evaluate quantitative analysis of
      99mTc-labeled 2-methoxyisobutyl isonitrile (MIBI) myocardial perfusion imaging
      combined with isosorbide dinitrate (ISDN) infusion to detect myocardial viability
      in patients with chronic coronary artery disease before and after
      revascularization. METHODS AND RESULTS: Twenty-seven consecutive patients with
      previous myocardial infarction and left ventricular dysfunction (left ventricular
      ejection fraction 35.2% +/- 13.5%) referred for coronary artery bypass (CABG)
      were studied with 99mTc-labeled MIBI single-photon emission computed tomography
      at rest and during ISDN infusion before CABG followed by resting imaging after
      CABG. Quantitative analysis was performed with circumferential profiles. Left
      ventricular function (global and regional) was assessed by radionuclide
      ventriculography before and after CABG. Out of 212 abnormal perfusion segments
      with resting 99mTc-labeled MIBI SPECT, 99 segments (47%) showed improved uptake
      of 99mTc-labeled MIBI during ISDN infusion. The mean ratio of myocardial uptake
      was 0.58 +/- 0.25 (resting 0.53 +/- 0.23; p < 0.05). After CABG, of 212 segments
      with hypoperfusion, 108 segments (51%; p > 0.05 vs ISDN) showed improved uptake
      of 99mTc-labeled MIBI. The mean ratio of myocardial uptake was 0.60 +/- 0.26
      (resting 0.53 +/- 0.23; p < 0.05). The concordance between the improvement of
      post-CABG wall motion and that of pre-CABG ISDN perfusion imaging was 83%,
      between the improvement of wall motion and perfusion imaging after CABG 94%, and
      between the improvement of pre-CABG ISDN and post-CABG perfusion imaging 83%,
      respectively. CONCLUSION: ISDN infusion can improve the uptake of 99mTc-labeled
      MIBI in hypoperfused myocardium and increase the efficiency of 99mTc-labeled MIBI
      in the detection of viable myocardium in patients with previous myocardial
      infarction and left ventricular dysfunction.

PMID- 8989671
TI  - Diagnostic value and incremental contribution of bicycle exercise, first-pass
      radionuclide angiography, and 99mTc-labeled sestamibi single-photon emission
      computed tomography in the identification of coronary artery disease in patients
      without infarction.
AB  - BACKGROUND: The diagnostic value and incremental contribution of different
      noninvasive tests to the identification of coronary artery disease in 128
      patients from a general population with intermediate pretest likelihood (48.0%)
      were determined by ordered logistic regression analysis and receiver-operating
      characteristic (ROC) curves. METHODS AND RESULTS: Patients referred for suspicion
      of coronary heart disease were submitted to bicycle exercise testing under
      clinical and electrocardiographic control. AT peak exercise, first-pass
      radionuclide angiography was performed after injection of 99mTc-labeled
      sestamibi, followed by single-photon emission computed tomographic (SPECT)
      acquisition. A comparative rest study was obtained within 1 week, and qualitative
      and quantitative analysis was applied to assess the presence and extent of
      disease. With coronary angiography and 50% stenosis used as a standard, the
      discriminative accuracy of each test was calculated. The accuracies to diagnose
      coronary heart disease were 71.3% +/- 4.7% for the bicycle test, 66.7% +/- 5.3%
      for radionuclide angiography, and 81.6% +/- 3.9% for the SPECT data. By ROC
      curves, the optimal criteria for positivity were determined for the visual and
      quantitative analysis for both presence and extent of coronary artery disease.
      Results of visual and quantitative SPECT were compared in terms of area under the
      ROC curves. The diagnostic performances showed no significant difference, ranging
      from 74.3% to 81.6%. The first-pass radionuclide angiographic and SPECT data were
      added progressively to the stress testing to evaluate their incremental
      diagnostic contribution. Only the addition of SPECT results significantly
      increased the accuracy to 85.6% +/- 3.3% (p < 0.0001). CONCLUSION: Exercise
      electrocardiography and first-pass radionuclide angiography showed comparable
      accuracy to detect coronary artery disease. However, the combination of exercise
      testing and visual SPECT analytic data sufficed to ensure diagnostic accuracy,
      without significant benefit from the addition of other tests or the application
      of quantification.

PMID- 8989672
TI  - Automation of gated tomographic left ventricular ejection fraction.
AB  - BACKGROUND: The feasibility of determining left ventricular (LV) ejection
      fraction (EF) from 99mTc-labeled sestamibi gated tomography (GSPECT) is well
      established. To improve precision of measurement, rules used by observers in
      processing tomograms were encoded for automation. METHODS AND RESULTS: LV centers
      were estimated from activity centroids of time-difference images exceeding 50% of
      maximum counts. End diastole and end systole were defined by time-varying maximum
      count extremes. Endocardial borders were generated by fitting maximum locations
      with fifth-order two-dimensional harmonics, searching inward to predetermined
      thresholds, and reconciling endocardial with valve plane points. Regression
      analysis of GSPECT EF yielded r = 0.87 versus equilibrium gated blood pool in 75
      patients and r = 0.87 versus gated first pass in 65 patients. GSPECT EF
      interobserver variability was r = 0.92 and intraobserver automatic versus manual
      linear correlation was r = 0.94. A subgroup of 25 studies was analyzed by six
      independent observers, for whom EF agreement with the core laboratory ranged from
      r = 0.93 to r = 0.96. Experienced observers judged it necessary to alter end
      diastolic or end-systolic frames in 7% of patients, endocardial borders in 14%,
      and LV centers in 28%. CONCLUSION: Results of automated GSPECT LV EF correlated
      well with those of manual GSPECT and gated first-pass and equilibrium blood pool
      values and were highly reproducible.

PMID- 8989673
TI  - Quantitative comparison of single-isotope and dual-isotope stress-rest single
      photon emission computed tomographic imaging for reversibility of defects.
AB  - BACKGROUND: Dual-isotope rest/stress single-photon emission computed tomographic
      (SPECT) imaging is a time-saving imaging protocol. However, the stress
      radiotracer, technetium 99m-labeled sestamibi, and the rest radiotracer, thallium
      201, have different physical properties and myocardial kinetics. In patients with
      abnormal resting myocardial perfusion, these differences may affect
      quantification of rest defect size and defect reversibility. The purpose of the
      study was to compare myocardial perfusion defect reversibility quantitatively by
      single-isotope (rest/stress sestamibi) and dual-isotope (rest thallium/stress
      sestamibi) SPECT. METHODS AND RESULTS: Thirty patients with prior myocardial
      infarction underwent rest/stress sestamibi SPECT imaging and rest thallium SPECT
      imaging. Defects were quantified according to circumferential count profiles with
      a normal sestamibi database. The images of a subgroup of 21 patients were
      processed with radiotracer-specific normal databases. Defect size and defect
      reversibility were compared quantitatively for single-isotope and dual-isotope
      SPECT. Rest sestamibi defect size was significantly larger than rest thallium
      defect size (19 +/- 15 vs 14 +/- 16; p = 0.007). Defect reversibility was larger
      with thallium than with sestamibi (10 +/- 9 vs 6 +/- 6; p = 0.002). With
      radiotracer-specific normal databases, mean rest sestamibi and thallium defect
      sizes in 21 patients were not different (23 +/- 19 vs 21 +/- 17; difference not
      significant). With radiotracer-specific normal databases, mean defect
      reversibility was not different with either sestamibi or thallium (6 +/- 6 vs 8
      +/- 9; difference not significant), although correlation among individual
      patients was only fair (r2 = 0.48). CONCLUSION: In patients with prior myocardial
      infarction, stress-induced defect reversibility is quantitatively larger with
      dual-isotope imaging than with single-isotope imaging. Quantitative processing of
      dual-isotope images requires radiotracer-specific normal databases. Because of
      different characteristics of sestamibi and thallium, assessment of defect
      reversibility on dual-isotope images should be made with caution. Only relatively
      large defect reversibility can be assumed to represent true stress-induced
      myocardial ischemia.

PMID- 8989674
TI  - Estimation of myocardial blood flow for longitudinal studies with 13N-labeled
      ammonia and positron emission tomography.
AB  - BACKGROUND: Although several modeling strategies have been developed and
      validated for quantification of myocardial blood flow (MBF) from 13N-labeled
      ammonia positron emission tomographic data, a comparison of noise characteristics
      of the various techniques in serial studies is lacking. METHODS AND RESULTS:
      Dynamic 13N-labeled ammonia positron emission tomographic imaging was performed
      at baseline and after pharmacologic stress in (1) single studies of four dogs
      with concomitant measurement of microsphere blood flow and (2) initial and follow
      up studies of eight normal volunteers. Data were obtained from short-axis images
      for the blood pool and myocardial regions corresponding to the three arterial
      vascular territories. Indexes of MBF were obtained by four distinct techniques:
      (1) University of California, Los Angeles, two-compartment model, (2) Michigan
      two-compartment model, and (3) a one-compartment model with variable blood volume
      term. Coronary flow reserve (CFR) was measured as the ratio of stress/rest MBF.
      The estimated standard deviation of the measurement error for the relative change
      between studies of rest and stress MBF and CFR was determined for each technique.
      Estimates of MBF from all techniques showed good correlation with microsphere
      blood flow (r = 0.95 to 0.96) in canine myocardium. In human studies, similar
      mean estimates of MBF were found with all techniques. Techniques 1 and 3 showed
      the smallest interstudy variability in MBF and CFR. The estimated standard
      deviations for these techniques were approximately 20%, 30%, and 27% for rest
      MBF, stress MBF, and CFR, respectively. CONCLUSION: Noninvasive quantification of
      MBF and CFR from dynamic 13N-labeled ammonia positron emission tomography is most
      reproducible with technique 1 or 3. The ability to account for differences in
      myocardial partial volume gives preference to technique 3. However, substantial
      interstudy variability in regional MBF remains, suggesting the importance of
      procedural factors or real temporal fluctuations in MBF.

PMID- 8989675
TI  - Abnormal myocardial uptake and clearance of 123I-labeled metaiodobenzylguanidine
      in patients with chronic renal failure and autonomic dysfunction.
AB  - BACKGROUND: Patients with chronic renal failure were evaluated with 123I-labeled
      metaiodobenzylguanidine (MIBG) myocardial scintigraphy to investigate the
      relationship between abnormal findings on MIBG scintigrams and autonomic
      dysfunction. METHODS AND RESULTS: Eleven control subjects and 20 patients with
      chronic renal failure (CRF) (serum creatinine level > 8 mg/dl) were evaluated by
      MIBG myocardial scintigraphy and power spectral analysis (PSA) of the R-R
      fluctuations of the electrocardiogram. Subjects with CRF were divided into two
      groups: without (CRF1; nine patients) or with (CRF2; 11 patients) autonomic
      neuropathy. From MIBG images, the heart/mediastinum mean count rate, defect
      score, which was scored visually, and clearance rate were calculated. Percent low
      frequency power and high-frequency power were obtained from PSA. MIBG scintigrams
      showed decreased heart/mediastinum mean count rate, a high defect score in both
      initial and delayed images, and rapid clearance rate in the CRF2 group. PSA
      showed an abnormally low percent low-frequency power and high-frequency power in
      the CRF2 group. In addition, there was a weak but significant inverse correlation
      between percent low-frequency power and defect score. CONCLUSION: Alterations in
      MIBG scintigrams are seen in patients with autonomic dysfunction in CRF and may
      be useful for evaluating cardiac sympathetic dysfunction in those patients.

PMID- 8989678
TI  - Acute radionuclide perfusion imaging for evaluation of chest pain in the
      emergency department: need for a large clinical trial.

PMID- 8989677
TI  - A primer of biostatistic and economic methods for diagnostic and prognostic
      modeling in nuclear cardiology: Part I.
AB  - This review presents a brief overview of existing diagnostic and prognostic
      methodologies to be used for the evaluation of patients undergoing noninvasive
      testing. In part I of this review, we will present methods for use of logistic
      and Cox regression analyses in determining the diagnostic and prognostic value of
      nuclear imaging techniques. In part II of this review, we will present an outline
      for the integration of economic evaluations into the clinical decision-making
      process. This review will document how cost estimates may be defined as well as
      the differing type of cost analyses (i.e., cost efficiency versus cost
      effectiveness).

PMID- 8989679
TI  - Successful treatment of vasospastic angina and symptomatic polymorphic
      ventricular tachycardia with calcium antagonists and nitrates based on a
      diagnosis made with exercise 201Tl imaging.

PMID- 8989676
TI  - Prognostic value of myocardial perfusion imaging: state of the art and new
      developments.
AB  - Although the prognostic value of myocardial perfusion imaging is now well
      established, new data have continued to expand its role in the management of
      patients. This review addresses the current state-of-the-art and new developments
      in the use of myocardial perfusion imaging for determining cardiac risk and
      integrating such information into patient care.

PMID- 8989681
TI  - Pharmacologic stress versus maximal-exercise stress for perfusion imaging: which,
      when, and why?

PMID- 8989680
TI  - Validation of noninvasive studies for detecting coronary artery disease: beauty
      versus blood flow.

PMID- 8989682
TI  - Tracer selection with different stress modalities based on tracer kinetics.

PMID- 8989683
TI  - Comparison of pharmacologic stress agents.
AB  - In choosing a pharmacologic agent for stress testing, the clinician must keep a
      number of things in mind, such as the diagnostic utility of the agent or in what
      situations a vasodilator or catecholamine will be the better choice. Although all
      stress agents produce similar diagnostic accuracy for CAD, vasodilators have a
      higher cardiac uptake than catecholamines, and the addition of exercise improves
      the heart/background contrast ratios. With regard to physiologic comparisons,
      exercise or dobutamine will double coronary perfusion compared with baseline
      flow, but vasodilators produce a threefold or fourfold increase. The clinician
      should also keep in mind that adenosine will produce the shortest duration of
      hyperemia, whereas dobutamine and arbutamine produce a longer effect, and
      dipyridamole has the longest duration. If electrophysiologic considerations are
      important, exercise and catecholamines accelerate sinoatrial and atrioventricular
      conduction and are not typically associated with heart block. In contrast,
      adenosine can cause transient atrioventricular block, but this rarely occurs with
      dipyridamole. Clinical factors also must be considered. Although clinical utility
      of pharmacologic stress agents in the first 24 hours after infarction has not
      been demonstrated, the prognostic utility of vasodilators in the subsequent 2- to
      4-day period has been shown. With patients with pulmonary disease (asthma) who do
      not have wheezing, dipyridamole can be used, but dobutamine or arbutamine should
      be used in patients with recent respiratory failure or bronchospasm before
      testing. In patients with left bundle branch block, vasodilators are the
      preferred stress agents rather than synthetic catecholamines or dynamic exercise.
      In the first crossover thallium imaging, there was good overall agreement in
      segmental perfusion comparing adenosine and dipyridamole, but there was a
      tendency for adenosine to detect more ischemia. The clinical significance (if
      any) for these findings has yet to be determined.

PMID- 8989685
TI  - Are separate normal data files required for quantitative pharmacologic stress
      radionuclide myocardial perfusion imaging?

PMID- 8989684
TI  - Pharmacology of coronary vasodilation: a brief review.
AB  - Successful scintigraphic imaging of coronary artery stenosis is dependent on
      detecting regional differences (nonhomogeneous distribution) in coronary blood
      flow that can be induced by physiologic or pharmacologic stress. Table 1
      represents a summary of major pharmacologic responses of the heart to the four
      agents discussed above. Both adenosine and dipyridamole produce superior coronary
      vasodilation and tend to be preferred for use in single-photon emission computed
      tomography, whereas dobutamine and arbutamine provoke a marked ischemic response
      and tend to be preferred for use in echocardiography. Which agent employed
      remains a judgment of the physician based on known side effects of these agents,
      the patient's ability to tolerate these side effects, and the nature of the test
      desired.

PMID- 8989686
TI  - Risk assessment in patients with stable coronary artery disease: incremental
      value of nuclear imaging.

PMID- 8989687
TI  - Risk assessment after myocardial infarction: have the rules changed with
      thrombolytic therapy?.

PMID- 8989688
TI  - Absolute quantitation of myocardial blood flow: the technical and clinical
      prospects for single-photon emission computed tomography.

PMID- 8989690
TI  - Clubfoot: what have we learned in the last quarter century?

PMID- 8989689
TI  - The role of stress echocardiography versus stress perfusion: a view from the
      other side.

PMID- 8989691
TI  - Surgical management of ankle valgus in children: use of a transphyseal medial
      malleolar screw.
AB  - Valgus deformity of the ankle in children is associated with a wide variety of
      clinical conditions. A retrospective review was performed of 17 children (29
      involved extremities) with ankle valgus deformity who had been managed by use of
      a percutaneously placed, transphyseal medial malleolar screw. Median age at the
      time of surgery was 11 years, 2 months. Median postoperative follow-up was 2
      years, 2 months. Tibiotalar axis and ankle mechanical axis were the best
      radiographic indicators of ankle valgus deformity. Fibular station and epiphyseal
      wedging were poor predictors of ankle alignment. Significant improvement in the
      tibiotalar axis (median, 12 degrees) was noted at follow-up, and the median rate
      of correction was 0.59 degree/month. Resumption of physeal growth and recurrence
      of deformity (rate of 0.60 degree/month) was seen when the screws were removed
      before skeletal maturity. The transphyseal medial malleolar screw is a minimally
      invasive, minimally morbid, technically simple method of reversible partial
      epiphysiodesis at the ankle and is an effective technique for the correction of
      ankle valgus deformity associated with a wide variety of clinical conditions in
      children.

PMID- 8989692
TI  - Screw epiphysiodesis for ankle valgus.
AB  - Progressive ankle valgus is an insidious deformity that may develop during
      childhood due to a variety of etiologies including neuromuscular disease,
      skeletal dysplasia, chromosomal anomalies, and clubfoot. This may be concomitant
      with, or mistaken for, hindfoot valgus. The surgical options for treatment
      include supramalleolar osteotomy or hemiepiphysiodesis of the medial distal
      tibial physis. We report the rationale and technique of retarding medial
      malleolar growth by means of inserting a single 4.5-mm vertical screw. In a
      population of 31 children (50 feet), we have observed satisfactory improvement of
      ankle valgus with low morbidity and without permanent physeal closure. This
      represents a safe, predictable, and effective solution for children who present
      with progressive and symptomatic ankle valgus.

PMID- 8989693
TI  - Talocalcaneal coalition resection: a 10-year follow-up.
AB  - Eight patients (nine feet) who underwent resection of persistently symptomatic
      talocalcaneal middle-facet coalitions were reevaluated > or = 10 years after
      surgery. Satisfactory results persisted in eight of nine cases with no
      deterioration of symptom relief. There was no loss of motion or development of
      degenerative joint changes. No patient required a secondary surgery. It appears
      that resection of symptomatic talocalcaneal coalition provides satisfactory
      results in the majority of patients, and its benefits are maintained 10 years
      after the procedure.

PMID- 8989695
TI  - A simple demonstration of hindfoot flexibility in the cavovarus foot.
AB  - A simple prone examination for demonstrating both hindfoot flexibility and the
      "tripod" effect in the cavovarus foot has been implemented. This clinical
      evaluation can be performed without the use of any special equipment. Prone
      positioning also allows easy demonstration of deformity to family members.

PMID- 8989694
TI  - Plantar fibromatosis of the heel in children: a report of 14 cases.
AB  - Based on a study of 14 patients younger than 16 years, we found that lumps on the
      plantar aspect of the anteromedial portion of the heel pad can safely be
      observed. Many remained small and asymptomatic, some disappeared, and two that
      required repeated excision biopsy did not subsequently recur. The six patients
      who were subjected to excision biopsy were found to have plantar fibromatosis.
      This very precise heel site is a characteristic situation for plantar
      fibromatosis in childhood.

PMID- 8989696
TI  - Foot deformities at birth: a longitudinal prospective study over a 16-year
      period.
AB  - In a prospective study of 2,401 newborns, the incidence of foot deformities was
      4%, of which three fourths were various forms of adductus anomalies. At age 16
      years, the children with a foot deformity and a random sample of those with
      normal feet as newborns were examined by dynamic foot pressure (EMED) and gait
      analysis (Vifor). The natural course of all congenital foot deformities, except
      clubfoot, was favorable. The importance of monitoring the children during the
      entire growth period is shown by the fact that at age 6 years, 87%, and at 16
      years, 95% of the adductus deformities had resolved.

PMID- 8989697
TI  - Residual bone cysts after correction of severe foot deformities with the Ilizarov
      technique.
AB  - Fourteen patients with severe foot deformity treated by application of the
      Ilizarov device were evaluated for residual bone changes in the foot. Cyst
      formation was noted in all patients, most commonly in the base of the fifth
      metatarsal. These cysts did not develop in the area of bone penetrated by the
      wires. In an average follow-up of 3.4 years after device removal, the cysts did
      not resolve. Histologic examination of one resected cyst demonstrated an empty
      lacuna with no cell lining, as seen in the "cysts" associated with
      osteoarthrosis.

PMID- 8989698
TI  - A comparison of the long-term results of posterior and comprehensive release in
      the treatment of clubfoot.
AB  - This study compared the long-term results of posterior and comprehensive release
      in the treatment of clubfoot. Patients were eligible for this study if the
      clubfoot was idiopathic and treatment was performed before 2 years of age.
      Medical records were reviewed to obtain the age, sex, bilaterality, and details
      of surgical treatment. Posterior release (performed before 1971) consisted of
      Achilles tendon lengthening and posterior ankle and subtalar releases. The
      comprehensive release, as described by Carroll, was performed after 1972. At the
      time of final review, patients completed Ponsetti's functional 100-point grading
      system, were examined, and had foot radiographs performed. Of 81 eligible
      patients, 59 (72%) were reviewed. Children in the two groups were not
      significantly different at the time of surgery for age, sex, and bilaterality.
      The patients were evaluated an average of 28 years (range, 25-30) after surgery
      in the posterior-release group and 16 years (range, 13-20) after surgery in the
      comprehensive-release group. Ponsetti scores were higher in the comprehensive
      release group (mean, 86 vs. 81) but were not significantly different (p = 0.13).
      The comprehensive-release group required fewer procedures per patient compared
      with the posterior-release group (1.5 procedures vs. 2.0; p = 0.04). The ankle
      range of motion was similar in the two groups (p = 0.12), but the percentage of
      patients with subtalar stiffness was higher in the posterior-release group (50
      vs. 18%; p = 0.01). Although the two groups were not statistically different
      based on the function-weighted Ponsetti scale, the comprehensive group had fewer
      operations, more complete correction of heel varus, and improved subtalar motion.

PMID- 8989699
TI  - Onset of ossification of the tarsal bones in congenital clubfoot.
AB  - Subjects of this study were 45 patients with 56 idiopathic congenital clubfeet
      (34 boys with 42 feet and 11 girls with 14 feet) who underwent successful
      conservative treatment. Radiologic examinations were performed at intervals of 3
      months. In anteroposterior radiographs of bilateral feet, the period of
      appearance of the ossification center was observed for the first, second, and
      third cuneiform and the tarsal navicular. The ossification of the tarsal bones in
      the congenital clubfeet occurred later than that in the unaffected feet in boys.
      The difference between the clubfeet and the unaffected feet was particularly
      statistically significant for the tarsal navicular and the second cuneiform (p <
      0.01). The tarsal naviculars, the first cuneiforms, and the second cuneiforms in
      clubfeet and in unaffected feet started to be ossified significantly earlier in
      girls than in boys. Ossification occurred out of order in three of 56 clubfeet
      and three of 34 unaffected feet.

PMID- 8989700
TI  - Surgical correction of angular deformity of the knee in children with renal
      osteodystrophy.
AB  - Twenty-nine children with renal osteodystrophy (RO) and angular deformities about
      the knee were studied, including 19 in whom 36 corrective operations were
      performed. Corrective osteotomy of the distal femur was performed in 20 knees,
      osteotomy of the proximal tibia in 11 knees, combined femoral/tibial osteotomy in
      three knees, and medial physeal stapling in two knees. The indication for surgery
      was a deformity significant enough to interfere with gait. Complications occurred
      in three patients and recurrence severe enough to require repeated surgery
      occurred in four patients. Patients who required repeated osteotomy appeared to
      have had poor metabolic control during the initial surgery, as measured by an
      increased alkaline phosphatase. Surgery for children with RO and knee deformities
      is quite feasible but requires careful surgical planning and preoperative
      metabolic stabilization. Whether to correct the femur or tibia can be determined
      by evaluating full-length films of the lower extremities.

PMID- 8989701
TI  - The cartilaginous femoral sulcus in children with patellar dislocation: an
      ultrasonographic study.
AB  - One hundred and sixteen knees of 33 patients with patellar dislocation and 25
      normal children 12-18 years of age were examined by ultrasonography to measure
      the cartilaginous sulcus angle on the patellar surface of the femur. In knees
      with patellar dislocation, the cartilaginous sulcus angle measured between 154
      and 195 degrees, exceeding the corresponding values of normal knees (134-153
      degrees). In patient knees, the cartilaginous sulcus was also consistently wider
      than the underlying osseous sulcus. This suggests that in pediatric patients with
      patellar dislocation, the actual patella-stabilizing ability of the femoral
      sulcus is weaker than the osseous outline in axial radiographs would lead one to
      suppose. It would appear also that by measuring the cartilaginous sulcus angle of
      the femur, a clear distinction can be made between normal knee joints and joints
      displaying patellar instability.

PMID- 8989702
TI  - Treatment of adolescent Blount disease by asymmetric physeal distraction.
AB  - An alternative treatment is presented for late-onset Blount disease in a 14-year
      old boy. The technique consists of asymmetric physeal distraction of the proximal
      tibial growth plate by using a modified Wagner fixator-distractor device that
      allows progressive angular correction. The patient had a 23 degrees varus
      deviation of the left tibia, and no physeal bone bridges were detected. Once the
      fixator was assembled, distraction started 24 h after surgery at a rate of 1.5
      mm/day (2 x 0.75). Complete correction was achieved in 25 days. No osteotomy of
      the fibula was required. The Wagner device was removed in the outpatient clinic
      10 weeks postoperatively. After a 4-year follow-up, there was no loss of
      correction, showing a satisfactory alignment of the operated-on lower extremity.
      As compared with acute conventional osteotomies, asymmetric physeal distraction
      entails several advantages for treatment of Blount disease such as less invasive
      surgery, progressive and adjustable correction taking place at the apex of the
      deformity, and the possibility of bone lengthening if needed. Furthermore,
      physeal distraction does not require a second surgical step for bonegraft
      harvesting or for removal of the internal fixation.

PMID- 8989703
TI  - Congenital dislocation of the knee reduced spontaneously or with minimal
      treatment.
AB  - Six cases of congenital dislocation of the knee (CDK) reduced spontaneously or
      with minimal treatment were investigated. Reduction was achieved from 4 days to 3
      months after birth. Clinical results were good, although in four cases,
      hyperextension < or = 20 degrees persisted. In view of the perinatal
      complications and associated anomalies, CDK reduced with no or minimal treatment
      is supposed to be a category of congenital postural deformity. We believe that it
      is advisable to wait 1 month for spontaneous reduction of CDK in cases not
      associated with clubfoot, arthrogryposis multiplex congenita, and Larsen's
      syndrome.

PMID- 8989704
TI  - Radiologic study of patellar height in Osgood-Schlatter disease.
AB  - There are contradictory reports regarding patellar position in the Osgood
      Schlatter disease. We present a prospective statistical study of 17 patients with
      Osgood-Schlatter disease and 12 adolescents without anterior knee pain. The Caton
      Deschamps index was assessed on strictly the lateral radiograph of the knee. The
      findings indicate a strong association between Osgood-Schlatter disease and
      patella alta. This increase in patellar height would require an increase in the
      force needed from the quadriceps to achieve full extension. This mechanism could
      be responsible for the apophyseal lesion.

PMID- 8989705
TI  - Management of the completely stiff pediatric knee.
AB  - The purpose of this study was to ascertain whether aggressive surgical treatment
      of ankylosed knees, followed by immediate continuous passive motion (CPM), can
      restore acceptable function in children. A retrospective analysis was performed
      on five children operated on for severely contracted knees. In all cases,
      extensive intraarticular pathology was present, and lysis of adhesions, tendon
      lengthenings, and capsular releases were performed in each case. Cruciate
      ligament release, drilling of subchondral bone, and patellectomy or meniscectomy
      or both also were performed in certain cases. Surgery was followed by immediate
      CPM for 6 weeks. Knee motion improved significantly from a preoperative mean of 7
      degrees (range, 0-20 degrees) to 63 degrees (range, 15-90 degrees) at final
      follow-up, and all patients were satisfied with the result. The mean follow-up
      interval was 4.6 years. The regenerative properties of articular cartilage as
      well as the physis in the skeletally immature may permit a radically different
      approach from that accepted in adults. Such an approach can spare the native
      joint and restore acceptable function.

PMID- 8989706
TI  - Synovial hemangioma of the knee.
AB  - Hemangioma of the knee is a cause of pain and recurrent hemarthroses in the
      pediatric age group, often seen as an internal derangement of the knee.
      Historically, long delays in diagnosis have occurred. Conventional radiographic
      techniques can miss the presence of the lesion. However, magnetic resonance
      imaging (MRI) is a noninvasive and frequently diagnostic investigative modality.
      Five cases of diffuse synovial hemangioma of the knee are presented. Diffuse
      lesions are difficult to excise arthroscopically, and open wide excision is
      recommended after MRI and arthroscopic assessment.

PMID- 8989707
TI  - The hamstring index.
AB  - The purpose of this study was to assess the limits of hamstring tightness in 369
      children by using three common tests. The straight leg-raise test averaged 100
      degrees at birth, increasing to 110 degrees at age 1 year, before decreasing to
      80 degrees by age 5-6 years. It then remained constant to skeletal maturity.
      Hamstring tightness is present if this angle is < 80 degrees in children younger
      than 2 years. After this age, the limit decreased steadily to plateau at 60
      degrees by the age of 6 years. The popliteal angle measured the maximum 180
      degrees from birth to age 2 years. This angle then decreased to average 155
      degrees by age 6 years and remained steady. An angle < 125 degrees suggests
      significant hamstring tightness. The touching-toes test showed minimal variation
      between age groups averaging, 1 +/- 3 cm. Distances reached < -5 cm in children
      aged up to 6 years and < -15 cm in those older than 6 indicate excessively tight
      hamstrings. Little difference was seen between sides, although girls demonstrated
      less hamstring tightness. All tests showed a positive correlation with the grade
      of ligamentous laxity, but no association with the child's stage of puberty could
      be detected.

PMID- 8989708
TI  - Complications of anterior spinal surgery in children.
AB  - The purpose of this study was to document the medical and surgical complications
      of anterior spine surgery in children and to identify risk factors for
      complications. A retrospective chart review was conducted of 599 anterior
      procedures (24 anterior only, 300 staged anterior/posterior, 175 combined
      anterior/posterior procedures) performed between 1967 and 1991. Major
      complications occurred in 7.5% of procedures and minor complications in 33%. Risk
      factors for major complications were age > 14 years, male gender, kyphotic curve
      type, curve sizes > 100 degrees, vital capacity < 40% of predicted, and use of
      thoracotomy. Risk factors for minor complications were age > 14 years, curves >
      100 degrees, vital capacity < 40% of predicted, and use of a staged procedure.
      Multivariate analyses of risk factors identified age > 14 years and curves > 100
      degrees as the most significant risk factors for major complications and age > 14
      years for minor complications. We concluded that anterior spinal surgery can be
      performed in children with an acceptable level of risk and that referral for
      surgery before 14 years of age and before the curve size progresses will
      significantly reduce the risk of complications.

PMID- 8989709
TI  - Hemivertebral excision for congenital scoliosis.
AB  - We retrospectively reviewed the cases of 10 consecutive patients treated with
      hemivertebral excision for congenital scoliosis at The Children's Hospital,
      Denver, CO, between 1982 and 1992. Follow-up consisted of physical and
      radiographic examination and averaged 54 months (range, 4-111). Age at surgery
      ranged from 9 months to 10 years, 5 months (average, 3 years, 11 months).
      Hemivertebra levels were between T12 and L3. The average preoperative curve
      measured 40 degrees (range, 20-55 degrees); the average at latest follow-up was
      16 degrees (range, 3-37 degrees). We found hemivertebral excision for congenital
      scoliosis to be a safe and effective means of treatment. Curve correction
      averaged 67% and seemed to be greatest in those less than 4 years of age at the
      time of surgery.

PMID- 8989710
TI  - Segmental spinal dysgenesis: early neurologic deterioration and treatment.
AB  - Segmental spinal dysgenesis is a rare congenital condition of the lumbar or
      thoracolumbar spine that can be associated with significant progressive or
      permanent neurologic defects, including paraplegia. In the past, both bracing and
      surgery have been recommended. Of the seven children we have seen with this
      problem, three have lost motor function between presentation and the time of
      surgery. Our experience suggests that to prevent catastrophic neurologic
      deterioration, surgery is indicated once the diagnosis is made.

PMID- 8989711
TI  - Abdominal reflexes.
AB  - Examination of the superficial abdominal reflexes in patients thought to have
      idiopathic scoliosis has been considered possibly beneficial for deciding who
      should have magnetic resonance imaging to rule out syringomyelia. The purpose of
      this study was to determine what is normal for this examination. Thirty normal
      adolescents and 35 normal young adults underwent testing of the superficial
      abdominal reflexes and the patellar and Achilles deep tendon reflexes. Each test
      was repeated two times. Thirty-nine (60%) subjects had bilaterally equal
      abdominal reflexes. Nine (14%) subjects had asymmetric reflexes, and seven (11%)
      subjects had no reflex in at least one quadrant. No subjects had reflexes present
      on one side and absent on the other. Ten (15%) subjects had absence of the
      abdominal reflexes in all quadrants. Sixteen (25%) subjects had extinguishing of
      the reflex in at least one quadrant as the test was repeated. Eleven of these had
      asymmetric or partially absent reflexes initially. In contrast, the patellar and
      Achilles reflexes were more consistent. The patellar reflexes were bilaterally
      equal in 52 (85%), asymmetric in eight (13%), and absent in one (2%). The
      Achilles reflexes were bilaterally equal in 59 (97%), asymmetric in one (2%), and
      absent in one (2%). The finding of abdominal reflexes consistently present on one
      side and consistently absent on the other side did not occur in our normal
      subjects. This finding might warrant further workup if found in a patient with
      scoliosis. Other variations in abdominal reflex testing such as asymmetries,
      absent in some quadrants, and absent in all quadrants are fairly common in normal
      subjects.

PMID- 8989712
TI  - Complications after posterior spinal fusion in Duchenne's muscular dystrophy.
AB  - Patients with Duchenne's muscular dystrophy often develop progressive scoliosis.
      Should spinal stabilization be necessary, these patients are considered at high
      risk for surgically related complications. This retrospective study of 30
      patients with Duchenne's examined the prevalence and types of complications
      associated with posterior spinal fusion and determined the percentage of patients
      who lived > or = 2 years beyond surgery. Major complications related to
      cardiopulmonary compromise, infection, or hardware complications occurred in 27%,
      and minor complications occurred in another 16%. Seventy-seven percent of the
      patients lived > or = 2 years beyond their surgery. The majority of patients and
      their families, including half of those who had major complications, reported
      that surgery resulted in an improvement in their quality of life. Although
      complications are common, the benefits realized by the patient with Duchenne's
      muscular dystrophy with scoliosis reinforce the importance of surgical
      stabilization.

PMID- 8989713
TI  - Vertebral growth after thoracic or lumbar fracture of the spine in children.
AB  - We studied vertebral growth after thoracic or lumbar fractures in 52 children
      followed up from the time of fracture until skeletal maturity. We identified pure
      anterior compression in 32, combined anterior and lateral compression in 11, and
      total vertical compression in nine. Six patients had no treatment, 42 had a
      conservative treatment, and four were operated on. In fractures with anterior
      compression < 10 degrees, no significant difference could be found between the
      group without treatment and the group with conservative treatment when the Risser
      sign was 0 or 1 at the time of injury. In such fractures with angles > 10
      degrees, conservative treatment gave better results when the Risser sign at
      injury was < or = 2. Prolonged conservative treatment was not effective in
      children with a Risser sign of 3. The evolution of lateral compression seems to
      be related to the initial injury rather than to treatment. Vertical compression
      injuries were positively influenced by a conservative treatment when the Risser
      sign was < or = 2.

PMID- 8989715
TI  - Premature closure of the distal radial physics after fracture of the distal
      radial metaphysis.

PMID- 8989714
TI  - Mechanical evaluation of four- versus eight-pin halo fixation.
AB  - Fixation of the halo device in the skulls of young children is sometimes
      compromised because of a thinner cortex and the increased jarring and trauma that
      small children experience during their everyday activities of life at that age.
      To assess the increased fixation that an eight-pin halo fixation would provide
      over the more standard four-pin fixation, the stiffness of fixation of a halo
      orthosis was evaluated in four dried human cadaver skulls. Two different fixation
      systems were used: the first one with four pins in the standard locations and the
      second with four additional pins. A compressive force was applied to the halo
      ring at a constant rate of 1.27 mm/min. Load and deflection data were recorded
      simultaneously until a force of 400 N was reached. Results for the two-pin
      systems were analyzed and compared statistically by using paired t tests.
      Statistically significant differences were established between the two sets of
      results with the 8-pin system providing an increase of 24.2% in the stiffness of
      fixation.

PMID- 8989716
TI  - Supracondylar fractures of the humerus in children: treatment by overhead
      skeletal traction.

PMID- 8989717
TI  - Use of melatonin in the treatment of paediatric sleep disorders.
AB  - A group of Vancouver health professionals, including the authors, have studied
      the use of oral melatonin in the treatment of chronic sleep disorders in children
      with disabilities since the Fall of 1991. This review article is based on the
      first 100 patients, half of whom were visually impaired or blind. Children with
      neurological, neuropsychiatric, and developmental disabilities are predisposed to
      chronic sleep-wake cycle disturbances. Disorders such as blindness, deaf
      blindness, mental retardation, autism, and central nervous system diseases, among
      others, diminish the ability of these individuals to perceive and interpret the
      multitude of cues for synchronizing their sleep with the environment. Melatonin,
      which benefitted slightly over 80% of our patients, appears to be a safe,
      inexpensive, and a very effective treatment of sleep-wake cycle disorders. The
      oral dose of fast release melatonin taken at bed-time ranged from 2.5 mg to 10
      mg. Side effects or the development of tolerance have not been observed. Since
      the causes of sleep difficulties are extremely variable, not all children are
      candidates for treatment. For successful melatonin treatment, clinical experience
      is required, and the influences of other health problems and medications need to
      be considered. Further clinical and laboratory research in this field is
      imperative because melatonin treatment offers enormous health, emotional, social,
      and economic benefits to society, especially since multidisabled children with
      chronic sleep difficulties do not respond well to current therapeutic regimes.

PMID- 8989718
TI  - Melatonin in relation to physiology in adult humans.
AB  - The role exerted by melatonin in human physiology has not been completely
      ascertained. Melatonin levels have been measured in different physiopathological
      conditions, but the effects induced by melatonin administration or withdrawal
      have been tested only recently. Some effects have been clearly documented.
      Melatonin has hypothermic properties, and its nocturnal secretion generates about
      40% of the amplitude of the circadian body temperature rhythm. Melatonin has
      sleep inducing properties, and exerts important activities in the regulation of
      circadian rhythms. Melatonin is capable of phase shifting human circadian
      rhythms, of entraining free-running circadian rhythms, and of antagonizing phase
      shifts induced by nighttime exposure to light. Its effect on human reproduction
      is not completely clear, but stimulatory effects on gonadotropin secretion have
      been reported in the follicular phase of the menstrual cycle. Direct actions on
      ovarian cells and spermatozoa have been also documented. Beside these, new
      important actions for melatonin may be proved. Melatonin may exert protective
      effects on the cardiovascular system, by reducing the risk of atherosclerosis and
      hypertension, and may influence immune responses. Finally, by acting as an
      antioxidant, melatonin could be important in slowing the processes of ageing.

PMID- 8989719
TI  - Melatonin reduces mortality from Aleutian disease in mink (Mustela vison).
AB  - Aleutian disease (AD) results from a persistent parvoviral infection that results
      in marked hypergammaglobulinemia and immune complex mediated lesions of the
      kidney, liver, lungs and, arteries. Melatonin protected both a wild type or demi
      strain and a demi/dark crossed strain of mink from AD. The biogenic amine also
      afforded protection against other non-diagnosed diseases naturally found on mink
      farms when it was available from a subcutaneously-placed reservoir. Some genetic
      strains of mink apparently differed in the resistance of mink to the virus and in
      the protective ability of melatonin. The demi strain was the most resistant
      followed by pastels, mahogany, darks, and those strains with the double recessive
      Aleutian gene. The protective action of melatonin appeared to result from
      melatonin's ability to scavenge free radicals, but it could also be due to the
      induction of antioxidant enzymes or to the modulation of immunity. Melatonin also
      protected mink against distemper.

PMID- 8989720
TI  - Melatonin secretion in rams maintained in constant darkness depends on the timing
      of a single 1-hour light pulse given the previous night.
AB  - Previous data have demonstrated that a single 1-hr light pulse at night affects
      the secretion of melatonin in the ram if it was given at the appropriate time.
      This paper reports the effect on melatonin secretion of a 1-hr light pulse given
      at two different times at night to two groups of rams kept in constant darkness
      the day following light application. It appears that the animals were able to
      remember the light pulse if it was given 12 hr but not 9 hr after the lights were
      turned off. This memory could possibly be stored in the suprachiasmatic nucleus
      as reported recently in the rat.

PMID- 8989721
TI  - 6-Hydroxymelatonin sulfate excretion in human puberty.
AB  - We investigated the relationship of urinary excretion rate of 6-hydroxymelatonin
      sulfate (SM), the main metabolite of melatonin, with pubertal development and
      determined the day to day variability of SM excretion. Healthy subjects 4-31
      years old completed one or multiple timed overnight urine collections. SM
      excretion rate per body size was significantly higher in 99 prepubertal subjects
      (35.5 +/- 2.3 ng/h/kg and 0.97 +/- 0.06 microgram/hr/m2) than in 86 pubertal
      subjects (18.1 +/- 1.1 ng/hr/kg and 0.61 +/- 0.03 microgram/hr/m2) or in 29
      adults (15.0 +/- 1.5 ng/hr/kg and 0.59 +/- 0.06 microgram/hr/m2); no significant
      difference was present in pubertal stages 2 to 5. Among the prepubertal children,
      SM excretion rate in mid childhood was significantly higher than in late
      childhood. The variability of SM and creatinine excretion examined in 52
      children, adolescents and adults with three or four collections was defined as
      the mean of the 52 coefficients of variation for the multiple measures in each
      subject. The variability of total nocturnal SM (25.9 +/- 2.6%) was similar to
      that of total creatinine (21.7 +/- 2.3%) and neither was significantly correlated
      with the variability in start time or duration of urine collection. The results
      suggest that, relative to body size, melatonin secretion rate is higher in mid
      childhood, decreases during late childhood, and remains stable from pubertal
      stage 2 to adulthood. The decline in melatonin secretion rate occurs during the
      developmental phase of disinhibition of the gonadotropin releasing hormone pulse
      generator. Hence, we infer that melatonin may be a suppressive factor of puberty
      during childhood. The substantial individual variability observed for SM
      excretion calls for caution in using single urine collections in longitudinal
      studies or in studies of drug responses.

PMID- 8989722
TI  - Afternoon injections of melatonin in the Djungarian hamster Phodopus sungorus:
      long lasting sex-specific effects and influence of acute treatment on the
      endogenous pineal melatonin rhythm.
AB  - The effects of exogenous melatonin on gonadal function and on the endogenous
      melatonin profiles of male and female Djungarian hamsters were investigated.
      Daily afternoon subcutaneous injections of melatonin (50 micrograms) in hamsters
      kept in long photoperiods (LD 16:8) led to gonadal inhibition in all the treated
      females (n = 13) but in only 2 of 13 males within the treatment period of 8 weeks
      (uteri: 244 +/- 11 mg in controls vs. 79 +/- 4 mg in treated hamsters, P < 0.001;
      ovaries: 13.6 +/- 0.6 mg in controls vs. 7.9 +/- 0.7 mg in treated hamsters, P <
      0.001; testes: 1,021 +/- 54 mg in controls vs. 732 +/- 100 mg in treated
      hamsters, P < 0.05; and accessory glands: 641 +/- 38 mg in controls vs. 548 +/-
      70 mg in treated hamsters, P > 0.05). These results indicate that there are some
      circumstances under which the gonadal responses of the reproductive organs of
      male and female Djungarian hamsters differ. Interestingly, pineal concentrations
      of melatonin were found to be significantly higher in males (P < 0.01), possibly
      indicating a more robust endogenous supply with the hormone, whereas serum
      melatonin levels were not significantly different between males and females.
      However, the subcutaneous injection of melatonin (5, 25, and 125 micrograms)
      exerted no acute effect on the endogenous, circadian melatonin-profile,
      independent of dosage and sex.

PMID- 8989723
TI  - Adjuvant therapy with the pineal hormone melatonin in patients with lymph node
      relapse due to malignant melanoma.
AB  - Several experimental studies have shown that melatonin has an oncostatic action,
      either by stimulating host antitumor immune defenses or by directly inhibiting
      the growth of some cancer histotypes, including melanoma. Our previous clinical
      studies demonstrated that melatonin may induce stabilization of the disease in
      untreatable metastatic solid tumor patients, and these results have been
      confirmed by others, at least in patients with metastatic melanoma. On the
      contrary, at present there are no data related to the possible efficacy of
      melatonin as an adjuvant endocrine therapy. This study was performed to
      investigate the impact of melatonin therapy on the disease-free survival (DFS) in
      melanoma patients surgically treated for regional node recurrence. The study
      included 30 node-relapsed melanoma patients, who were randomized to receive no
      treatment or adjuvant therapy of melatonin (20 mg/day orally in the evening)
      every day until disease progression. After a median follow up of 31 months, the
      percent of DFS was significantly higher in melatonin-treated individuals than in
      controls. The DFS curve was also significantly longer in melatonin group than in
      controls. No melatonin-related toxicity was observed. This preliminary study
      suggests that an adjuvant endocrine therapy with melatonin may be effective in
      preventing disease progression in node-relapsed melanoma patients.

PMID- 8989724
TI  - 6-Sulphatoxymelatonin secretion in different locomotor activity types of the
      blind mole rat Spalax ehrenbergi.
AB  - 6-Sulphatoxymelatonin (aMT6S) excretion was examined in the urine of rhythmic and
      arrhythmic blind subterranean mole rats (Spalax ehrenbergi) to test the
      correlation between melatonin secretion (as represented by aMT6S) and variability
      in circadian locomotor activity. Activity pattern was tested in four males, first
      for a week under short photoperiod [light:dark (LD) 10:14], followed by 10 days
      in constant darkness (DD). After several months the experiment was repeated under
      long photoperiod (LD 14:10), followed by DD conditions. Under LD conditions all
      animals exhibited aMT6S excretion during the dark phase, with a decline just
      before the onset of light. No correlation was found between activity pattern and
      melatonin secretion. The animal with the highest melatonin secretion both under
      LD and DD had an arrhythmic locomotor pattern. The results suggest that in mole
      rats melatonin secretion and circadian locomotor activity are controlled by two
      different mechanisms. There were large differences in the aMT6S levels among
      individuals, suggesting the importance of duration of melatonin secretion over
      amplitude for gonadal development and thermoregulatory changes. During summer,
      i.e., before the breeding season, the animals keep a more stable aMT6S secretion
      than in winter, and the amplitude of secretion is higher under DD vs. LD
      conditions.

PMID- 8989725
TI  - Melatonin concentrations in serum and tissues of porcine gastrointestinal tract
      and their relationship to the intake and passage of food.
AB  - Melatonin concentrations were determined in serum and 10 segments of the
      gastrointestinal tract (GIT) of 48 pigs (100 kg weight). The animals were fasted
      for 30 hr and then sacrificed 0, 1, 2, 5, 10, and 20 hr after refeeding. Peak
      amount of gastric digesta (2,428 g) and ileum digesta (850 g) were observed 1 hr
      and 5 hr, after refeeding, respectively. Conversely, colon content reached a
      minimal weight (726 g) at 2 hr after refeeding. Serum levels of melatonin
      increased from 3.4 pg/ml to 15.5 pg/ml (peak 5 hr after refeeding). Melatonin
      levels in GIT tissues before refeeding varied from 23.8 pg/g (stomach-fundus) to
      62.1 pg/g (rectum). Increasingly higher levels of melatonin were detected in the
      distal segments of the GIT. Higher melatonin levels after refeeding were observed
      in most GIT tissues except the rectum. In most tissues, peak melatonin values
      were detected 5 hr after refeeding. A significant change in weight of digesta
      across time (P < 0.05) was detected in the stomach, ileum, and cecum. Similar
      changes in melatonin levels across time were found in most tissues except the
      esophagus, stomach (cardia and pylorus), and rectum. Adjacent GIT tissues
      exhibited similar (P < 0.05) melatonin levels. The GIT melatonin levels
      correlated best with the variation of digesta weight in the ileum. In addition,
      the increase of serum melatonin levels correlated best with the increase of GIT
      melatonin levels in the distal part of the GIT. Our results suggest that
      melatonin produced in the ileum, cecum, and colon may contribute significantly to
      the short-term increase of serum melatonin levels observed after refeeding.

PMID- 8989726
TI  - Polymorphism in the beta subunit and Na+ transport.
AB  - Primary dysregulation of the epithelial sodium channel, manifested by continuing
      Na+ channel activity despite dietary salt excess, would cause inappropriate renal
      sodium reabsorption, blunted sodium excretion, and low-renin hypertension. There
      are now well-characterized genetic causes of hypertension in human pedigrees,
      which are explained by inappropriate and/or constitutive activation of the
      epithelial Na+ channel. Although Liddle's syndrome has been the most thoroughly
      investigated, the incidence of such activating mutations in the subunits of the
      Na+ channel appears to be relatively rare. Of continuing interest is the
      possibility that polymorphisms in the channel subunits could result in activation
      of the channel in response to normal regulatory influences. One such example is
      provided by a provocative report by Su et al. In this issue of the journal (J Am
      Soc Nephrol 1996;7:2543-2549). Despite several important technical limitations of
      the findings presented in the article, the suggestion that polymorphisms found in
      defined human populations would affect the regulation of sodium channel activity
      in response to environmental variables is worthy of serious consideration, and
      serves as a further stimulus to defining the functional significance of the
      various polymorphisms described in the subunits of the amiloride-sensitive sodium
      channel.

PMID- 8989727
TI  - Molecular insights into renal interstitial fibrosis.
AB  - Progressive interstitial fibrosis accompanied by loss of renal tubules and
      interstitial capillaries typifies all progressive renal diseases. Dynamic and
      complex, the process evidently overlaps with matrix remodeling; it may even be
      reversible. The interstitial fibrous tissue comprises several normal and novel
      matrix proteins, proteoglycans, and glycoproteins. Interstitial myofibroblasts
      are a major site of matrix protein overproduction, although resident fibroblasts,
      tubular cells, and inflammatory cells may contribute. Inadequate matrix
      degradation also appears to contribute to the fibrogenic process. Two protease
      cascades, the metalloproteinases and the plasminogen activator/ plasmin family of
      serine proteases, are implicated in the turnover of interstitial matrix proteins;
      upregulated expression of protease inhibitors has been observed in each.
      Increased tissue inhibitor of metalloproteinase-1 and plasminogen activator
      inhibitor-1 levels suggest that the intrinsic renal activity of the
      metalloproteinases and serine proteases are inhibited while matrix proteins
      accumulate in the interstitium. Several signals that may direct the interstitial
      fibrogenic process have been identified, but not yet proved to cause it.
      Upregulated expression of transforming growth factor beta-1, the proteotypic
      fibrogenic cytokine, has been observed in experimental and human models; it
      probably does not act alone. There may be supportive roles for platelet-derived
      growth factor, interleukin-1, basic fibroblast growth factor, angiotensin II, and
      endothelin-1. Although it is not known why interstitial fibrosis compromises
      renal function, atrophy of renal tubules may be pivotal. Ischemic necrosis and/or
      apoptosis may generate nonfunctioning atubular and sclerotic glomeruli. Future
      studies must delineate the molecular basis of the differences between renal
      repair and renal destruction by fibrosis, two processes that share many common
      features.

PMID- 8989728
TI  - Genetics of diabetic nephropathy.
AB  - Diabetic nephropathy is a clinical syndrome characterized by persistent
      albuminuria, a relentless decline in GFR, raised arterial blood pressure, and
      increased relative mortality for cardiovascular diseases. Diabetic nephropathy is
      a leading cause of end-stage renal failure. The pathogenesis of diabetic
      nephropathy is multifactorial, with contributions from metabolic abnormalities,
      hemodynamic alterations, and various growth factors and genetic factors.
      Epidemiologic and family studies have demonstrated that only a subset of the
      patients develop this complication that family clustering of nephropathy is
      present, and that ethnicity plays an important role in the risk of developing
      this kidney disease. Short stature and low birth weight are both associated with
      increased risk of developing diabetic nephropathy, supporting the hypothesis that
      genetic predisposition or factors operating in utero, in early childhood, or both
      contribute to the development of diabetic nephropathy. Studies elucidating
      phenotypic markers such as parenteral hypertension and systemic blood pressure
      elevation have yielded conflicting results. The contribution from elevated blood
      pressure only plays a minor role in the majority of the patients developing
      diabetic nephropathy. The majority of the studies have demonstrated increased
      sodium/lithium countertransport activity in insulin-dependent diabetes mellitus
      patients with nephropathy, whereas studies of this phenotypic marker in parents
      of patients with and without nephropathy have yielded conflicting results.
      Recently, studies of genetic markers involved in the regulation of blood pressure
      and levels of cardiovascular risk factors have been conducted. Several studies
      have demonstrated that the deletion polymorphism in the angiotensin-I-converting
      enzyme acts as a risk factor for cardiovascular disease in diabetic patients.
      However, a meta-analysis does not support the suggestion that this factor plays
      any role for the initiation of diabetic nephropathy. Similar negative results
      have been obtained in relation to polymorphisms of the genes encoding for
      angiotensinogen and the angiotensin II Type 1 receptor. However, studies in
      diabetic and non-diabetic glomerulopathies have clearly demonstrated a
      deleterious effect of the deletion polymorphism in the angiotensin-converting
      enzyme on the progression of kidney function.

PMID- 8989729
TI  - Molecular mechanisms of glomerular injury in rat experimental membranous
      nephropathy (Heymann nephritis)
AB  - The molecular pathogenesis of human membranous nephropathy (MN) is unknown,
      despite the relatively high incidence and severity of this glomerular immune
      disease. Heymann nephritis (HN) in rats is considered an instructive experimental
      model of MN. This study summarizes current molecular aspects of two key events
      common to both MN and HN, i.e., formation of characteristic subepithelial immune
      deposits in the glomerular basement membrane (GBM), and development of glomerular
      capillary wall damage resulting in proteinuria. In HN, the antigenic targets of
      immune deposit-forming antibodies were identified in cell membranes of glomerular
      epithelial cells as a 515-kd glycoprotein (megalin, or gp330), which is a
      polyspecific receptor related to the low-density lipoprotein receptor family, and
      an associated 44-kd protein (receptor associated protein, RAP). One epitope was
      recently narrowed to 14 amino acids in RAP, and several others on megalin/gp330
      are under investigation. Proteinuria requires formation of the complement C5b-9
      membrane attack complex, which is presumably triggered by antibodies directed
      against lipid antigens that associate with immune deposit-forming megalin/gp330
      immune complexes. Sublytic C5b-9 attack on glomerular epithelial cells causes
      upregulation of expression of the NADPH oxidoreductase enzyme complex by
      glomerular cells, which is translocated to their cell surfaces, similar to
      activated neutrophil granulocytes in the respiratory burst reaction.
      Subsequently, reactive oxygen species (ROS) are produced locally, which reach the
      GBM matrix. Here formation of lipid peroxidation (LPO) adducts is found,
      preferentially on monomeric and dimerized NCl domains of covalently crosslinked
      Type IV collagen. These structural changes within the GBM could be of functional
      relevance because treatment with the potent LPO-antagonist probucol reduces
      proteinuria by < 80%. Intact or fragmented apoprotein E-containing lipoproteins
      were identified as potential sources of the polyunsaturated lipids required for
      the production of LPO adducts. Lipoproteins accumulate within immune deposits and
      show signs of oxidative damage, similar to oxidized LDL within atherosclerotic
      lesions. Collectively, the results obtained so far in HN permit the compilation
      of a sequence of events, linking formation of immune deposits with proteinuria.
      However, despite this relatively detailed knowledge of pathogenic events in HN,
      the bridge to human NM remains to be built.

PMID- 8989730
TI  - Coexistence of central diabetes insipidus and salt wasting: the difficulties in
      diagnosis, changes in natremia, and treatment.
AB  - Both central diabetes insipidus (DI) and a high rate of excretion of sodium (Na)
      and chloride (Cl) contributed to the development of polyuria and dysnatremia in
      two patients during the acute postoperative period after neurosurgery. To
      minimize difficulties in diagnosis and projections for therapy, two available
      (but not often used) clinical tools were helpful. First, the osmole excretion
      rate early on revealed the co-existence of central DI and an osmotic diuresis.
      The osmoles excreted were largely Na salts; after antidiuretic hormone acted,
      this electrolyte diuresis caused the urine flow rate to be much higher than
      otherwise anticipated. Interestingly, part of this saline diuresis occurred when
      the extracellular fluid volume was contracted. The tool to explain the basis for
      the dysnatremias was a tonicity balance. Hypernatremia, which developed before
      treatment of central DI, was primarily a result of a positive balance for Na
      rather than a large negative balance for water. Moreover, hyponatremia that
      developed once antidiuretic hormone acted was primarily a result of a negative
      balance for Na; the urine volume was large and its Na concentration was
      hypertonic. To prevent a further decline in the plasma Na concentration, either
      the Na concentration in the urine should be decreased by provision of urea or a
      loop diuretic while replacing all unwanted water and electrolyte losses;
      alternatively, the fluid infused should have a similar Na concentration and
      volume as the urine (infuse hypertonic saline).

PMID- 8989731
TI  - Immunolocalization of the secretory isoform of Na-K-Cl cotransporter in rat renal
      intercalated cells.
AB  - Two bumetanide-sensitive ion cotransporters that carry Na+, K+, and Cl- in a
      coupled fashion have been identified. One type, the "absorptive" isoform, carries
      these ions across the apical plasma membrane of the thick ascending limb of
      Henle's loop. Another isoform, the "secretory" cotransporter, has been identified
      in a number of epithelial tissues by physiological means, but its sites of
      expression in the kidney have not been fully characterized. Complementary DNA
      believed to code for the secretory isoform (called "BSC2" or "NKCC1") have
      recently been cloned. This study used a specific affinity-purified antipeptide
      antibody to this protein for immunolocalization in the rat kidney. Immunoblot
      studies using this antibody show abundant immunoreactivity against bands of 140
      190 and 120 kd in the parotid gland, colon, and stomach, sites where the
      secretory form of the cotransporter has been identified by physiological
      techniques. This distribution supports the hypothesis that this isoform
      represents the secretory form of the cotransporter. Studies in the kidney
      revealed that the same bands are associated with membrane fractions chiefly in
      the outer medulla. Immunolocalizations show that immunoreactivity is selectively
      and intensely localized to the basolateral plasma membrane of a subfraction of
      outer medullary collecting duct cells. An independently produced monoclonal
      antibody (T4) specific for Na-K-Cl cotransporter displays the same localization.
      Dual localizations of cotransporter antibody with respect to antibody specific
      for principal cells (aquaporin-2) and intercalated cells (band 3 and H(+)-ATPase)
      show that cotransporter immunoreactivity is localized to alpha-intercalated cells
      of the outer medullary collecting duct in the rat. This distinctive localization
      suggests that the secretory form of the cotransporter may play a role in renal
      NH4+ and/or acid secretion by this cell type.

PMID- 8989732
TI  - A novel variant of the beta-subunit of the amiloride-sensitive sodium channel in
      African Americans.
AB  - The amiloride-sensitive sodium channel is responsible for the rate-limiting step
      of sodium reabsorption in the distal renal tubule, and thus may play a key role
      in the maintenance of sodium balance and blood pressure. In this study, a genetic
      variant that results in a change of threonine to methionine at amino acid 594
      (T594 M) in the carboxy-terminus of the beta-subunit of the amiloride-sensitive
      sodium channel has been identified. This variant was present in 6.1% of African
      American subjects (N = 231) but was not seen in Caucasians (N = 192). Whole cell
      voltage clamp of B-lymphocytes from individuals with the T594 M variant showed
      similar basal membrane slope conductance, compared with the wild-type but
      increased response to cAMP analog.

PMID- 8989733
TI  - The deletion polymorphism of the angiotensin I-converting enzyme gene is
      associated with target organ damage in essential hypertension.
AB  - The activity of the renin-angiotensin-aldosterone system is thought to play a
      significant role in the development of target organ damage in essential
      hypertension. An insertion/deletion (I/D) polymorphism of the angiotensin I
      converting enzyme (ACE) gene has recently been associated with increased risk for
      left ventricular hypertrophy and coronary heart disease in the general
      population. The D allele is associated with higher levels of circulating ACE and
      therefore may predispose to cardiovascular damage. The study presented here was
      performed to investigate the association between the ACE genotype,
      microalbuminuria, retinopathy, and left ventricular hypertrophy in 106 patients
      with essential hypertension. ACE gene polymorphism was determined by polymerase
      chain reaction technique. Microalbuminuria was evaluated as albumin-to-creatinine
      ratio (A/C) in three nonconsecutive first morning urine samples (negative urine
      culture) after a 4-wk washout period. Microalbuminuria was defined as A/C between
      2.38 to 19 (men) and 2.96 to 20 (women). Hypertensive retinopathy was evaluated
      by direct funduscopic examination (keith-Wagener-Barker classification) and left
      ventricular hypertrophy by M-B mode echocardiography. The distribution of the DD,
      ID, and II genotypes was 27, 50, and 23%, respectively. The prevalence of
      microalbuminuria, retinopathy, and left ventricular hypertrophy was 19, 74, and
      72% respectively. There were no differences among the three genotypes for age,
      known duration of disease, body mass index, blood pressure, serum glucose, uric
      acid, and lipid profile. DD and ID genotypes were significantly associated with
      the presence of microalbuminuria (odds ratio, 8.51; 95% confidence interval, 1.07
      to 67.85; P = 0.019), retinopathy (odds ratio, 5.19; 95% confidence interval,
      1.71 to 15.75; P = 0.005) and left ventricular hypertrophy (odds ratio, 5.22; 95%
      confidence interval, 1.52 to 17.94; P = 0.016). Furthermore, patients with DD and
      ID genotypes showed higher levels of A/C (3.6 +/- 0.9, DD; 2.6 +/- 0.7, ID; 0.9
      +/- 0.2 mg/mmol, II; P = 0.0015 by analysis of variance) and increased left
      ventricular mass index (152 +/- 4.7, DD + ID versus 133 +/- 5.7 g/m2, II; P =
      0.01) compared with II patients. The D allele was significantly more frequent in
      patients with microalbuminuria (odds ratio, 2.59; 95% confidence interval, 1.24
      to 5.41; P = 0.013) and in those with retinopathy (odds ratio, 2.44; 95%
      confidence interval, 1.21 to 4.90; P = 0.015). Multiple regression analyses
      performed among the entire cohort of patients demonstrated that ACE genotype
      significantly and independently influences the presence of retinopathy, left
      ventricular hypertrophy, and microalbuminuria. In conclusion, the D allele of the
      ACE gene is associated with microalbuminuria as well as with retinopathy and left
      ventricular hypertrophy, and seems to be an independent risk factor for target
      organ damage in essential hypertension.

PMID- 8989734
TI  - Linkage analysis between loci in the renin-angiotensin axis and end-stage renal
      disease in African Americans.
AB  - The factors that initiate chronic renal failure in patients with hypertension,
      diabetes mellitus, and chronic glomerular disease are largely unknown. The likely
      genetic contribution to ESRD, particularly in African Americans, suggests that
      linkage analysis may be useful to evaluate the role of candidate genes in the
      pathogenesis of chronic renal failure. The renin-angiotensin-aldosterone (RAA)
      axis has been intensively evaluated for its contribution to cardiovascular
      disease and nephropathy. This study tested for linkage between candidate genes in
      the RAA axis and chronic renal failure, using 85 African-American sibling pairs
      (from 65 families) concordant for ESRD. Angiotensinogen was selected because of
      the putative link between it and mild to moderate essential hypertension and
      nephrosclerosis; angiotensin-converting enzyme because of its possible
      contribution to diabetic nephropathy; and renin, the angiotensin II receptor, and
      kallikrein because of their roles in hypertension and renal perfusion. These
      candidate loci did not demonstrate linkage to either diabetic or nondiabetic
      renal disease in this study's collection of sibling pairs. These results suggest
      that polymorphisms at these RAA axis loci do not make major contributions to the
      pathogenesis of renal disease in African Americans.

PMID- 8989735
TI  - Impaired inactive to active kallikrein conversion in human salt-sensitive
      hypertension.
AB  - Active and inactive urinary kallikrein excretion rates were evaluated in 43
      essential hypertensive men (45.4 +/- 5.6 yr) after normal-(120 mmol/day), low-(20
      mmol/day), and high-(240 mmol/day) NaCl diets were given for 2 wk each. Patients
      were classified as salt-sensitive, salt-resistant, or counterregulating, on the
      basis of their blood pressure responses to the different NaCl intakes. Resulting
      data show that active and inactive kallikrein excretion rates were lower (P <
      0.001) in salt-sensitive (active, 0.59 +/- 0.27 U/24 h; inactive, 3.45 +/- 1.31
      U/24 h) than in salt-resistant (active, 1.41 +/- 0.35 U/24 h; inactive, 6.93 +/-
      2.68 U/24 h) and in counterregulating hypertensive patients (active, 1.37 +/-
      0.39 U/24 h; inactive, 6.32 +/- 2.58 U/24 h) after the normal NaCl diet. Salt
      sensitive hypertensive patients showed also higher plasma digoxin-like substance
      (P < 0.001), atrial natriuretic peptide (P < 0.001), and fasting insulin (P <
      0.005) levels than the other subgroups. Active kallikrein decreased after high
      and increased after low-NaCl intake in all groups. Inactive kallikrein varied
      similarly to active one in salt-resistant patients and counterregulating
      patients, whereas it increased during salt-loading in salt-sensitive patients.
      Consequently, the active/total kallikrein ratio decreased in salt-sensitive
      patients (from 20.2 +/- 3.5 to 5.82 +/- 1.02%, P < 0.05) when they switched from
      low- to high-NaCl intake, and the ratio was lower in these patients than in the
      other subgroups (P < 0.0001) after the high-NaCl diet. In conclusion, active and
      inactive kallikrein excretions after normal-NaCl intake are reduced in salt
      sensitive hypertensive patients. The divergent active and inactive kallikrein
      responses to dietary NaCl changes in salt-sensitive patients could indicate an
      impairment of inactive to active kallikrein conversion during NaCl loading as a
      new mechanism in human salt-sensitive hypertension.

PMID- 8989736
TI  - Transforming growth factor-beta 1 in hypertensive renal injury in Dahl salt
      sensitive rats.
AB  - The expression of transforming growth factor-beta 1 (TGF-beta 1) for hypertensive
      renal injury was investigated in Dahl salt-sensitive (Dahl-S) rats fed a high
      salt (HS; 8% NaCl) diet or a low-salt (LS; 0.3% NaCl) diet for 4 wk. The HS rats
      developed severe hypertension and renal damage, including glomerulosclerosis and
      arteriosclerosis. TGF-beta biosynthesis by isolated glomeruli, the TGF-beta
      localization, and the gene expression of TGF-beta 1, latent TGF-beta binding
      protein (LTBP), and TGF-beta receptors (Types I, II, and III) were compared
      between the HS rats and LS rats. A TGF-beta bioassay revealed that the isolated
      glomeruli from the HS rats secreted a larger amount of latent TGF-beta than those
      from the LS rats. Northern blotting analysis demonstrated that the HS diet led to
      the increases in cortical gene expression of TGF-beta 1, LTBP, and TGF-beta
      receptors, compared with the LS diet. The glomerular biosynthesis of fibronectin
      and plasminogen activator inhibitor-1 (PAI-1), and cortical mRNA expression for
      fibronectin, collagen I, and PAI-1 (which may be affected by TGF-beta) in the HS
      rats were elevated, compared with the LS rats. The latent TGF-beta immunostained
      by anti-LTBP antibody was localized on the sclerosing glomeruli and vascular
      walls. Furthermore, fibronectin, collagen I, and PAI-1 were also localized in the
      sclerotic area. The TGF-beta 1-positive cells, immunostained by antibody for
      latency-associated peptide of TGF-beta 1, increased in the glomeruli and vascular
      walls in the HS rats. These results thus suggested that TGF-beta 1 may be related
      to hypertensive renal injury in this model.

PMID- 8989737
TI  - Renal response to blood pressure elevation in normal and glomerulonephritic rats.
AB  - Concurrent renal disease appears to augment greatly the adverse effects of
      systemic hypertension on renal function and the development of
      glomerulosclerosis. This study examined the effects of systemic hypertension and
      treatment of hypertension in groups of normal non-nephritic rats and rats
      submitted to 16 wk of glomerulonephritis induced by the administration of anti
      glomerular basement membrane antibody. Hypertension was produced by application
      of a clip to the right renal artery and blood pressure was treated with an
      angiotensin-converting enzyme (ACE) inhibitor, quinapril. Glomerulosclerosis of
      two types developed: a diffuse type that is characteristic of anti-glomerular
      basement membrane glomerulonephritis, and a focal segmental glomerulosclerosis
      that is characteristic of systemic hypertension. Glomerulonephritis significantly
      reduced the capacity of ACE inhibitors to decrease systolic blood pressure in
      awake animals. In addition, glomerulonephritis produced significant effects on
      plasma angiotensin II concentrations, whereby ACE inhibition no longer lowered
      plasma angiotensin II levels and in fact produced an increase. Glomerular
      capillary hydrostatic pressure and hydrostatic pressure gradient correlated with
      systolic blood pressure and with the incidence of focal glomerulosclerosis in non
      nephritic rats. However, in glomerulonephritis, systolic blood pressure no longer
      correlated with glomerular capillary pressure, and glomerular capillary pressure
      no longer correlated with the development of glomerulosclerosis, although
      systolic blood pressure did correlate with the degree of focal segmental
      glomerulosclerosis. Concurrent glomerulonephritis strongly conditions the effects
      of superimposed hypertension by altering the relationship between systemic blood
      pressure and glomerular capillary hydrostatic pressure and by decreasing the
      response of hypertension to therapy.

PMID- 8989738
TI  - Focal glomerulosclerosis and maximal glomerular hypertrophy in human
      nephronopenia.
AB  - This study examines the relationship of the degree of glomerular hypertrophy in
      nephronopenia to the development of focal segmental glomerulosclerosis (FGS) in
      humans. To this end, group mean glomerular diameters in a variety of acquired and
      congenital nephronopenic states in native kidneys and long-surviving renal
      allografts with and without FGS were analyzed and compared. The results indicate
      that all groups of native nephronopenic kidneys without FGS develop significant
      and equivalent glomerular hypertrophy. By contrast, long-surviving renal
      allografts without FGS do not undergo glomerular hypertrophy. For groups with
      FGS, long-surviving renal homografts had a significantly smaller mean glomerular
      diameter when compared with any other group of native nephronopenic kidneys.
      There was no significant difference among group mean glomerular diameters of
      native nephronopenic kidneys with FGS. Pairwise comparisons in each category of
      nephronopenia indicated that, except in the groups with uninephrectomy, the mean
      glomerular diameters were significantly larger in those with FGS than without.
      These observations are interpreted to indicate that nephronopenic individuals
      with native kidneys, by undergoing glomerular hypertrophy, consume much or all
      their capacity for glomerular enlargement. This brings them closer to their
      maximal diameters at which FGS develops. Finally, long-surviving renal allografts
      without nephronopenic FGS do not undergo glomerular hypertrophy. However, when
      FGS develops in long-surviving allografts, it does so at glomerular diameters
      significantly smaller than in native nephronopenic kidneys, reflecting their
      decreased capacity to undergo glomerular hypertrophy, acquiring maximal diameters
      at a smaller dimension than native nephronopenic kidneys.

PMID- 8989739
TI  - Early influx of glomerular macrophages precedes glomerulosclerosis in the obese
      Zucker rat model.
AB  - Because hyperlipidemia and macrophage influx appear to play a key role in the
      genesis of renal glomerulosclerosis, this study examined the temporal
      relationship between hyperlipidemia (triglycerides and cholesterol), mononuclear
      cell influx, changes in glomerular structure, and expansion of the extracellular
      matrices in obese Zucker rats, which rapidly develop hyperlipidemia and
      spontaneous glomerulosclerosis. Lean and obese Zucker rats were fed a standard
      diet, and were euthanized at 14 days, 1, 3, 6, 9, and 12 months. Plasma lipid,
      insulin, and creatinine levels were measured, and the presence of inflammatory
      cells in the glomerulus was assessed by immunohistochemistry on kidney sections.
      Plasma lipids and insulin and macrophage density were significantly greater in
      obese than in lean rats as early as 1 month. Computer-assisted image analysis was
      used to evaluate the glomerular domain surface areas. The morphometric
      measurements showed that glomeruli of obese rats rapidly became hypertrophied
      after 3 months, as a result of a very large increase in the mesangial domain. The
      expression of genes for extracellular matrix components and inhibitors of
      extracellular matrix proteinases (TIMP-1 and TIMP-2) was monitored in
      microdissected glomeruli. Reverse transcription-polymerase chain reaction showed
      increases in mRNA for Type IV collagen and fibronectin and for the two
      metalloproteinase inhibitors, each of which might participate in this matrix
      expansion. Thus, the development of hyperlipidemia plus macrophage influx at a
      very early age may initiate a sequence of events leading to glomerulosclerosis
      later on.

PMID- 8989740
TI  - Effects of dietary protein restriction on the progression of moderate renal
      disease in the Modification of Diet in Renal Disease Study.
AB  - The Modification of Diet in Renal Disease (MDRD) Study consisted of two
      randomized controlled trials to determine the effects of dietary protein
      restriction and strict blood pressure control. In 255 patients with advanced
      renal disease (baseline GFR, 13 to 24 mL/min per 1.73 m2; Study B), secondary
      analyses demonstrated a correlation between achieved protein intake and rate of
      decline in GFR, consistent with a beneficial effect of a low-protein diet. In 585
      patients with moderate renal disease (baseline GFR, 25 to 55 mL/min per 1.73 m2;
      Study A), the primary analysis of the effect of the low-protein diet was
      inconclusive because of a nonlinear GFR decline and limited duration of follow
      up. A meta-analysis of recent controlled trials, including MDRD Study A,
      demonstrated a beneficial effect of a low-protein diet on the incidence of renal
      failure. The objective of these secondary analyses is to explore further the
      effect of dietary protein restriction in Study A. In these analyses, a total of
      585 patients were randomly assigned to follow either a low-protein diet (0.58
      g/kg per day) or a usual-protein diet (1.3 g/kg day). Outcomes included the rate
      of GFR decline, incidence of renal failure or death, and change in urine protein
      excretion. Analyses included comparisons of randomized groups and correlations of
      outcomes with achieved protein intake. The comparisons of randomized groups
      revealed a faster GFR decline during the first 4 months after assignment to the
      low-protein diet but no difference in the variability in GFR decline between the
      diet groups, indicating a uniform short-term effect of the low-protein diet on
      GFR, probably as a result of hemodynamic adjustments. After 4 months, the mean
      decline in GFR in the low-protein diet group was slower, and the variability of
      the rate of decline was smaller, than in the usual-protein diet group (ratio of
      standard deviations, 0.73; 95% confidence interval, 0.55 to 0.91; P < 0.01). This
      suggests a greater beneficial effect of the low-protein diet in patients with a
      more rapid GFR decline. The net effect of the low-protein diet on GFR decline
      over 3 yr was no significant change in mean GFR decline, but reduced variability
      of the decline (ratio of standard deviations, 0.76; 95% confidence interval, 0.60
      to 0.92; P < 0.01). Correlational analyses revealed trends similar to the
      comparisons of randomized groups. During the first 4 months, patients with a
      greater decline in protein intake (irrespective of diet group) had a greater
      decline in GFR; thereafter, patients with a lower protein intake had a slower GFR
      decline. Over 3 yr, there was no significant correlation between GFR decline and
      achieved protein intake. The correlation of protein intake with GFR decline after
      4 months was less strong than observed in Study B. The relative risk of death or
      renal failure was 0.65 (95% confidence interval, 0.38 to 1.10; P = 0.10) in
      patients assigned to the low-protein diet group compared with the usual-protein
      diet group, which is similar to that observed in the meta-analysis. During follow
      up, the increase in urine protein excretion was delayed in the low-protein diet
      group (P = 0.008) and in patients with lower achieved protein intake (P = 0.005).
      In summary, the absence of a significant difference between the diet groups in
      the mean change in GFR from baseline to 3 yr precludes a definitive conclusion of
      a beneficial effect of the diet intervention based solely on MDRD Study A.
      However, these secondary analyses are consistent with a beneficial effect of the
      low-protein diet to slow the GFR decline in patients with the most rapidly
      declining GFR and to reduce urine protein excretion. These results, together with
      the results of the recent meta-analysis (including MDRD Study A), provide some
      support for the hypothesis that dietary protein restriction slows the progression
      of moderate renal disease.

PMID- 8989741
TI  - Renal findings in patients with short-term type 2 diabetes.
AB  - Under semiambulatory conditions, 85 consecutive patients with the diagnosis of
      Type 2 diabetes of short duration (excluding patients with islet cell antibodies
      or maturity onset diabetes of the young) were admitted to a self-control training
      program and were examined in this study. A comprehensive renal assessment was
      performed, including evaluation of albumin excretion rate (AER), renal
      hemodynamics, blood pressure (BP) profile, and indicators of genetic risk. AER >
      or = 30 mg/24 h was found in 13 (15%) of patients; in two of these patients, AER
      was > or = 300 mg/24 h. By logistic regression, high HbA1, current smoking, and
      BP parameters were significantly correlated with an increased risk of
      microalbuminuria (MA). In a multiple linear regression model, accounting for 57%
      of total variance, HbA1, ERPF, and current smoking were significantly correlated
      with AER. Median GFR (Cin(inulin clearance) 136 mL/min per 1.73m2; range, 94 to
      194) and ERPF (Cpah(para-aminohippuric acid clearance) 733; range, 451 to 1328)
      were significantly higher in patients than in control subjects (upper 95th
      percentile, 131 and 706 mL/min per 1.73m2, respectively). In a multiple linear
      regression model, explaining 27% of total variance, age, AER, gender, and fasting
      blood glucose were significantly correlated to GFR. According to the criteria of
      average daytime BP > or = 135/85 mm Hg or 24-h BP > or = 130/80 mm Hg, 60% of
      patients were hypertensive (HT). Sixty-one percent of all patients (including 50%
      of the untreated normotensive patients) were "nondippers", i.e., < 15% nighttime
      decrease of mean arterial pressure. Either HT or nondipping was found in 79% of
      all patients, so that only 21% had a completely normal blood pressure profile.
      Ninety-four percent of untreated hypertensive patients had no MA. First-degree
      relatives of patients with MA compared with patients without MA had more frequent
      cardiovascular events (69% versus 31%). The risk of MA in diabetic patients with
      positive family history was amplified by poor glycemic control. MA, but not
      hypertension, was marginally related to K(m) of Na+/Li+ countertransport. It was
      concluded that (1) microalbuminuria is found in 15% of patients newly presenting
      with Type 2 diabetes; (2) a high proportion of patients exhibit hyperfiltration;
      (3) according to ambulatory BP only, 21% of patients have a completely normal
      circadian BP profile; (4) a family history of cardiovascular events interacts
      with glycemic control to increase the risk of MA.

PMID- 8989742
TI  - Distribution of integrin subunits in human diabetic kidneys.
AB  - Integrins are cell-surface protein receptors that participate in cell adhesion to
      multiple extracellular matrix ligands, and consist of alpha and beta chain
      heterodimers. This study examined altered integrin distribution in diabetic
      nephropathy by investigating 12 human diabetic kidney biopsies, which were
      compared with normal human kidney. Diabetic nephropathy is characterized by
      mesangial expansion and progressive thickening of the glomerular basement
      membrane. Based on morphometric studies of mesangial expansion, diabetic
      nephropathy was determined to be moderate or severe. Three different patterns (P)
      of altered intensity of integrin staining were observed. In the mesangial
      integrin P, the intensity of integrin subunit staining of mesangial cells (alpha
      1, alpha 2, alpha 3, beta 1, alpha V, alpha V beta 5) was increased in moderate
      diabetic nephropathy and further increased in severe diabetic nephropathy. In the
      epithelial integrin P, integrin subunits localized to epithelial cells (alpha V,
      beta 3, alpha V beta 3, alpha V beta 5) were increased to the same extent in
      moderate and severe diabetic nephropathy. In the endothelial integrin P, integrin
      subunits localized to endothelial cells (alpha 3, alpha 5, alpha 6, beta 1) were
      increased in moderate diabetic nephropathy but returned to normal kidney staining
      intensity in severe diabetic nephropathy. From these observations, it was
      concluded that there is significant alteration in the expression of integrin
      subunits in diabetic nephropathy that is related to the severity of diabetic
      mesangial expansion. Additionally, the spectrum of integrin subunit alteration
      appears to be unique to individual glomerular cell types. Given the role of
      integrins in cell-surface interactions with extracellular matrix components,
      abnormalities in the expression of these molecules may be important in the
      pathogenesis of diabetic nephropathy.

PMID- 8989743
TI  - Increased energy expenditure in hemodialysis patients.
AB  - Malnutrition is prevalent in chronic hemodialysis patients and is related to
      multiple factors; the hemodialysis procedure itself has been suggested as a
      catabolic factor. To examine the possible role of hemodialysis on energy
      metabolism, resting energy expenditure and respiratory quotient in ten chronic
      hemodialysis patients was measured in this study, using a whole-room indirect
      calorimeter. Measurements were done continuously: for 2 h before hemodialysis,
      during 4 h of hemodialysis, for 2 h after hemodialysis, and separately on a
      nondialysis day after 12 h of fasting. Age-, sex-, and body mass index-matched
      healthy volunteers were used as control subjects. Chronic hemodialysis patients
      have a significantly higher resting energy expenditure on a nondialysis day (1.18
      +/- 0.15 kcal/min; P < 0.01) as compared with control subjects (1.10 +/- 0.16
      kcal/ min). Resting energy expenditure further increased significantly during the
      hemodialysis procedure (1.32 +/- 0.18 kcal/min, averaged over the 4 h of
      hemodialysis; P < 0.01 versus predialysis) and was also significantly higher
      compared with the postdialysis period and nondialysis day resting energy
      expenditure (P < 0.001 for both). This effect was most pronounced during the
      first (1.37 +/- 0.19 kcal/min) and second (1.33 +/- 0.18 kcal/min) hours of
      hemodialysis (P < 0.001 for both). Respiratory quotient was not significantly
      affected by hemodialysis. It was concluded that chronic hemodialysis patients
      have higher than normal resting energy expenditure levels, which is further
      increased during hemodialysis. This process may significantly potentiate the
      protein-calorie malnutrition seen in this patient population.

PMID- 8989744
TI  - The evaluation of iron status in hemodialysis patients.
AB  - Effective treatment of anemia in hemodialysis patients requires ongoing
      monitoring of iron status. The purpose of this study was to determine levels of
      commonly used iron indices predictive of iron deficiency in this population.
      Forty-seven patients with baseline serum ferritin levels < 600 ng/mL were treated
      with intravenous iron dextran (INFeD; Schein Pharmaceutical Inc., Florham Park,
      NJ), 1000 mg over ten hemodialysis treatments. Patients whose hematocrit value
      increased by 5% or who had a 10% decrease in their erythropoietin dose by 2
      months were classified as having iron deficiency (N = 31; 66%). All other
      subjects were classified as having adequate iron (N = 16; 34%). There was no
      statistically significant difference in baseline serum ferritin, transferrin
      saturation, mean cell volume, mean cell hemoglobin content, or red cell
      distribution width between the two groups. Receiver operator curves demonstrated
      that none of the iron indices had a high level of utility (both sensitivity and
      specificity > 80%). Two tests had marginal utility, serum ferritin at a level of
      < 150 ng/mL, and transferrin saturation < 21%. It was concluded that because of
      the tests' marginal utility, they should only be interpreted in the context of
      the patient's underlying erythropoietin, responsiveness. In patients who are
      responsive to erythropoietin, a transferrin saturation value < 18% or serum
      ferritin level < 100 ng/mL should be used to indicate inadequate iron. When
      erythropoietin resistance is present, transferrin saturation of < 27% or serum
      ferritin < 300 ng/mL should be used to guide iron management.

PMID- 8989745
TI  - Predialysis systolic blood pressure correlates strongly with mean 24-hour
      systolic blood pressure and left ventricular mass in stable hemodialysis
      patients.
AB  - This study used a 24-h ambulatory blood pressure (ABP) monitor to study the
      relationship between dialysis room-measured blood pressures (BP) and mean 24-h
      systolic and diastolic ambulatory BP (SABP and DABP) with left ventricular mass
      (LV) in a group of 35 stable hemodialysis patients. Predialysis and postdialysis
      systolic and diastolic blood pressure data were collected for the 12 dialysis
      treatments before the wearing of the ABP device, and the means of these values
      are reported. All patients were maintained on the same antihypertensive
      medications for 3 months before the study and had a stable hematocrit value of 30
      +/- 3% during this time period. There was no difference detected between daytime
      and nighttime ABP. SABP was a mean of 4.7 mm Hg below predialysis systolic BP (P
      = 0.004) and DABP was a mean of 3.7 mm Hg below predialysis diastolic BP. There
      was a strong correlation between SABP and predialysis systolic BP (r = 0.67, P =
      0.0001); however, postdialysis diastolic BP correlated better with DABP than did
      predialysis diastolic BP. In addition, LV mass correlated with SABP (r = 0.35, P
      = 0.03) and predialysis systolic BP (r = 0.35, P = 0.03). There was no apparent
      correlation between either pre- or postdialysis diastolic BP with LV mass. It was
      concluded that predialysis systolic BP and postdialysis diastolic BP correlates
      strongly with SABP and DABP. Furthermore, predialysis systolic BP correlates with
      LV mass in hemodialysis patients. If the deleterious effects of hypertension in
      this patient population are to be avoided, it is the predialysis systolic BP that
      needs to be controlled: It is insufficient to be satisfied with good postdialysis
      BP control, if patients are hypertensive before beginning dialysis.

PMID- 8989746
TI  - Vascular reactivity during combined ultrafiltration-hemodialysis: influence of
      dialysate-derived contaminants.
AB  - It has been suggested that hemodynamic instability and impaired vascular
      reactivity during combined ultrafiltration-hemodialysis are related to
      bioincompatibility factors such as dialysate-derived contaminants or the
      dialyzer. The study presented here investigated whether vascular reactivity could
      be improved by the use of sterile dialysate. Forearm vascular resistance and
      venous tone (measured by strain-gauge plethysmography) as well as arterial blood
      pressure (by Dinamap) and heart rate (by electrocardiogram) were measured in ten
      stable dialysis patients (age range, 28 to 71 yr) during 2 h of combined
      ultrafiltration-hemodialysis (bicarbonate; ultrafiltration rate 1.0 L/h). In
      addition, a dialysate sample was obtained for culture and limulus amebocyte
      lysate testing while blood was withdrawn for the estimation of plasma
      bactericidal/permeability increasing factor (measured by ELISA) and the soluble
      tumor necrosis factor receptor p75 (measured by ELISA). Patients served as their
      own control, comparing dialysis with nonsterile and sterile dialysate. No
      bacterial growth was observed in sterile dialysate, whereas all samples were
      positive for Pseudomonas in culture in nonsterile dialysis. All limulus amebocyte
      lysate tests were negative. Bactericidal/permeability increasing factor tended to
      increase during nonsterile dialysis (P = 0.063) and remained unchanged during
      sterile dialysis. In both treatments, tumor necrosis factor receptor p75
      increased significantly (P < 0.01). There were no significant differences in
      hemodynamic parameters between the treatment modalities. Despite use of sterile
      dialysate, forearm vascular resistance remained unchanged whereas venous tone
      decreased significantly. These results indicate that vascular reactivity during
      combined ultrafiltration-hemodialysis is not improved by the use of sterile
      dialysate.

PMID- 8989747
TI  - Association between heparan sulfate proteoglycan excretion and proteinuria after
      renal transplantation.
AB  - The aim of the study presented here was to investigate whether, in patients
      showing immediate graft function after renal transplantation, cold-ischemia and
      reperfusion lead to damage of the glomerular basement membrane and consequently
      to a loss of heparan sulfate proteoglycans. Loss of these heparan sulfate
      proteoglycans is a major cause of proteinuria. Time-dependent changes in urinary
      excretion rates of heparan sulfate proteoglycans but also of total protein,
      albumin, low- and high-molecular-weight proteins were analyzed quantitatively and
      by polyacrylamid-gel-electrophoresis in eight patients. Immediately after renal
      transplantation, severe proteinuria with an excretion rate of up to 251 +/- 108
      mg/min was apparent and rapidly declined within 24 h to 4.11 +/- 2.80 mg/min. The
      gel-electrophoretic pattern showed a nonselective glomerular and tubular
      proteinuria. The excretion rate of heparan sulfate proteoglycan was increased in
      this initial reperfusion phase (up to 7 h), most probably because of ischemia-
      and reperfusion-induced damage of the glomerular basement membrane. The initial
      nonselective glomerular proteinuria disappeared within 48 h, changing to a mild
      selective glomerular proteinuria. In this second phase (7 to 48 h), lower levels
      of heparan sulfate proteoglycan excretion were observed (0.54 +/- 0.54
      microgram/min versus 1.66 +/- 1.93 micrograms/min, P < 0.05). However, during the
      repair process of the glomerular basement membrane, heparan sulfate proteoglycan
      is synthesized de novo, leading to an increasing heparan sulfate proteoglycan
      content of the glomerular basement membrane. This second phase is paralleled by
      the change from a nonselective to a selective glomerular proteinuria. In the
      third phase, when the heparan sulfate proteoglycan content of the glomerular
      basement membrane normalizes, glomerular proteinuria was abolished in most of the
      patients.

PMID- 8989748
TI  - Acute cyclosporine-induced nephrotoxicity in renal transplant recipients: the
      role of the transplanted kidney.
AB  - Cyclosporine A causes an acute reduction in GFR. The interindividual variable
      reduction in GFR is most likely the result of arteriolar vasoconstriction.
      Vasoconstriction is attributable either to a local effect of cyclosporine on
      renal blood vessels (intrinsic mechanism) or to a systemic effect of cyclosporine
      on circulating and/or neuronal factors (extrinsic mechanism). The aim of the
      investigation presented here was to establish whether intrinsic or extrinsic
      mechanisms account for the interindividual differences in the susceptibility to
      acute cyclosporine-induced nephrotoxicity. For that purpose, this study took
      advantage of the clinical transplant situation in which two (intrinsically
      identical) kidneys from a cadaveric donor are transplanted into two
      (extrinsically) different subjects. The preexisting regular daily cyclosporine
      doses were raised by 25% for 2 wk and by 50% for another 2 wk in 16 patients with
      stable renal graft function, representing eight pairs of patients, each of whom
      had received kidneys from the same donor. In these patients, a mean (+/- SD)
      maximum cyclosporine-induced increase in serum creatinine concentration of 13 +/-
      11% (P < 0.001) and in serum BUN of 27 +/- 33% (P < 0.01), together with a
      decline in the fractional uric acid excretion of 51 +/- 89% (P < 0.02) were
      observed. The percentage change in serum creatinine concentrations after
      increased dosing of cyclosporine paralleled within the subjects receiving their
      kidneys from the same donor, i.e., when one recipient experienced a large
      percentage of change after increases of cyclosporine dosing, the corresponding
      recipient of a kidney from the same donor had a change of the same magnitude.
      Seven of eight pairs showed a consistent response with respect to a clinically
      significant increase in serum creatinine concentration of > 15%, with a
      consistent response purely by chance being < 5%. Thus, the transplanted kidney
      itself rather than the recipient determines the susceptibility to acute
      cyclosporine-induced nephrotoxicity.

PMID- 8989749
TI  - Biodistribution and clearance of 99mTc-labeled Arg-Gly-Asp (RGD) peptide in rats
      with ischemic acute renal failure.
AB  - Based on the previous demonstration of a renoprotective effect of arginine
      glycine-aspartic acid (RGD) peptides in acute renal failure, experiments were
      designed to test the distribution and renal accumulation of the peptide. To
      accomplish this goal, in this study, RGD peptide was radiolabeled and its
      biodistribution and renal accumulation was determined in rats with ischemic acute
      renal failure (ARF). 99mTc-RGD with or without 111In-DTPA were injected
      intravenously in control and ARF rats. Various organs were dissected at different
      times after injection and subjected to gamma-scintillation counting and
      autoradiography (ARG). Blood clearance of 99mTc-RGD was rapid, with t1/2 < 10
      min, and unchanged in ARF compared with control rats. Kidneys retained the
      largest portion of the injected dose in both control and ARF rats, as detected
      using scintillation counting and whole-body ARG (10.56 +/- 1.05% and 10.12 +/-
      3.16% injected dose/g wet weight, respectively). Renal ARG revealed a significant
      increase in binding to the cortex in ARF kidneys, compared with that of control
      kidneys. Given the differences in renal blood flow and GFR in control and
      postischemic kidneys, the next series of experiments was performed with two
      radiopharmaceuticals, 99mTc-RGD and 111In-DTPA. The ratio of 99mTc-RGD:111In-DTPA
      was increased more than three-fold in ARF kidneys compared with control kidneys
      (2.7 +/- 0.15 versus 0.8 +/- 0.19, respectively). The results indicate that (1)
      RGD peptide undergoes a rapid clearance predominantly via the renal route; (2)
      despite a significant reduction in the renal perfusion, 99mTc-RGD peptide
      accumulates in the postischemic kidney; (3) this is consistent with the
      hypothesis on the involvement of RGD-recognizing integrins in the development of
      tubular obstruction in renal ischemia.

PMID- 8989750
TI  - Glomerular filtration rate determined from a single plasma sample after
      intravenous iohexol injection: is it reliable?
AB  - The iohexol injection plasma clearance method is a good alternative to the inulin
      clearance method for determination of GFR, but requires multiple blood samples.
      To avoid this, methods have been developed which derive GFR from a formula that
      uses a single plasma concentration of the tracer and anthropometric data. The aim
      of this study was to evaluate whether a single plasma sample taken after iohexol
      injection allows reliable estimation of GFR. In this study, results of single
      point determination were compared with those obtained by multiple-point plasma
      clearance. The GFR of 686 outpatients with different degrees of renal function
      were recalculated by use of the Jacobsson formula. The optimum time for sampling
      was found at 10 h after injection of the marker for clearances < 40 mL/min per
      1.73 m2, 4 h for clearances between 40 and 99 mL/min per 1.73 m2, and 3 h for
      clearances > 100 mL/min per 1.73 m2. Results documented that for 75% of the
      patients, the simplified technique gave an error between -5% to +5% in the
      evaluation of GFR; for the remaining 25% of the patients, prediction error ranged
      from -22% to +40%. Furthermore, despite a highly significant correlation between
      multiple-point iohexol clearance (six plasma samples) and the single-point method
      (Y = 0.968X + 1.704, r2 = 0.988), the regression intercept was statistically
      different from 0 and the standard error of the slope estimate established that
      95% confidence interval did not include 1.0 (the line of identity), thus
      indicating that the model can be rejected by the data at a significance level of
      0.05. Thus the single-plasma-sample method to determine GFR after radiocontrast
      injection does not represent a real advantage over the multiple-point method and
      may lead to unacceptable errors in GFR calculation.

PMID- 8989751
TI  - Renal and pressor effects of aminoguanidine in cirrhotic rats with ascites.
AB  - Recent work indicates that nitric oxide (NO) plays an important role in the
      systemic and renal alterations of liver cirrhosis. This study used aminoguanidine
      (AG), a preferential inhibitor of inducible nitric oxide synthase (iNOS), to
      evaluate the role of this NOS isoform in the systemic and renal alterations of an
      experimental model of liver cirrhosis with ascites (carbon tetrachloride/
      phenobarbital). Experiments have been performed in anesthetized cirrhotic rats
      and their respective control rats prepared for clearance studies. Administration
      of AG (10 to 100 mg/kg, iv) elevated dose-dependent mean arterial pressure (MAP,
      in mm Hg) in the cirrhotic rats from a basal level of 79.3 +/- 3.6 to 115.0 +/-
      4.7, whereas in the control animals, MAP increased only with the highest dose of
      the inhibitor (from 121.8 +/- 3.6 to 133.3 +/- 1.4). In the cirrhotic group, AG
      also significantly increased sodium and water excretion, whereas these effects
      were very modest in the control group. Plasma concentration of nitrates+nitrites,
      measured as an index of NO production, were significantly increased in the
      cirrhotic animals in the basal period and decreased with AG to levels not
      significantly different from the control animals. Similar experiments performed
      with the nonspecific NOS inhibitor N omega-nitro-L-arginine (NNA) also
      demonstrated an increased pressor sensitivity of the cirrhotic rats, but the
      arterial hypotension was completely corrected. These results, in an experimental
      model of liver cirrhosis with ascites, show that AG exerts a beneficial effect as
      a result of inhibition of NO production, increasing blood pressure and improving
      the reduced excretory function. Because NNA, but not AG, completely normalized
      the arterial hypotension, it is suggested that the constitutive NOS isoform is
      also contributing in an important degree. It is concluded that the activation of
      both inducible and constitutive NOS isoforms plays an important role in the lower
      systemic blood pressure and associated abnormalities that characterize liver
      cirrhosis.

PMID- 8989752
TI  - Haplotype analysis of congenital nephrotic syndrome of the Finnish type in non
      Finnish families.
AB  - Congenital nephrotic syndrome of the Finnish type (CNF) has an estimated
      incidence of 1 in 8000 newborns in the genetically isolated population of
      Finland. Although the disease is most common in Finland, it occurs throughout the
      world in families without known Finnish origin. In the past, these authors
      recently localized the CNF gene to the chromosome 19q13.1 region and observed
      strong linkage disequilibrium to the genetic markers D19S610, D19S608, D19S224,
      and D19S220 in Finnish families. In these Finnish families, four main CNF
      haplotype categories have been observed. In the study presented here, haplotype
      analysis was applied to several non-Finnish CNF families to determine whether the
      same genetic locus is involved in these families. The results of the haplotype
      analysis suggest linkage to the 19q13.1 chromosomal region. It was also observed
      that, in most cases, alleles typically found on CNF chromosomes of Finnish
      families are also found on CNF chromosomes of non-Finnish families from North
      America and Europe. In these families, the strongest association was found with
      marker D19S608. These findings suggest that Finnish and many non-Finnish CNF
      cases share the same disease locus.

PMID- 8989753
TI  - The benefits and side-effects of ramped hypertonic sodium dialysis.

PMID- 8989754
TI  - Spiral CT of the thorax in daily practice: optimization of technique.
AB  - Effective utilization of spiral computed tomography (CT) technology in imaging of
      the thorax requires an understanding of technical parameters that affect image
      and scan quality. This article discusses how operator-controlled scan parameters
      can be optimized to achieve diagnostic and cost-effective examinations
      appropriate for daily clinical practice.

PMID- 8989755
TI  - Volumetric (helical/spiral) CT (VCT) of the airways.
AB  - Volumetric computed tomography (VCT) represents an important improvement over
      conventional CT for assessing most airway abnormalities. Elimination of
      misregistration due to variations in respiration coupled with decreased motion
      artifact and the ability to obtain routine overlapping sections allow a more
      confident estimation of the presence and extent of disease. Recently, attention
      has focused on newer reconstruction techniques including: multiplanar
      reconstructions (MPRs), including curved multiplanar reformations; multiplanar
      volume reconstructions (MPVRs) using ray projection techniques, such as maximum
      and minimum projection imaging; external rendering, or 3D-shaded surface
      displays; and, most recently, internal rendering or so-called "virtual
      bronchoscopy". Given the often redundant nature of many of these methodologies
      determining indications for their use remains to be established, especially by
      comparison to axial imaging. The purpose of this article is to review these
      various reconstruction techniques and, based on current knowledge, place them in
      an appropriate clinical context.

PMID- 8989756
TI  - Functional imaging of the airways.
AB  - The use of traditional pulmonary function tests (PFT) to assess airflow
      obstruction is limited by the fact that these measurements are global and can
      neither express the potential regional heterogeneity nor localize the
      distribution of airways involved. High-resolution computed tomography (HRCT) is
      an established technique for the detailed evaluation of the pulmonary parenchyma.
      The development of helical scanning techniques enables volume datasets to be
      acquired through regions of interest in a single breathhold. Acquired during
      different phases of suspended respiration or under different physiologic
      conditions, these image sets provide potential insights into the relationships
      between airway structure and function. Volumetric data in also amenable to
      advance image processing algorithms enabling more precise characterization of
      bronchial morphology. This review considers the challenge of assessing
      cardiopulmonary function due to the complexity of the heart and lungs. The
      considerable insights that have been gained about airway physiology in animal
      experimentation are discussed. Studies investigating the role of volume
      acquisition's Helical CT and Electron Beam CT techniques of evaluating functional
      small airways function in humans are reviewed in detail and potential methods for
      analysis of airflow obstruction and detection of airway reactivity are
      extensively considered.

PMID- 8989757
TI  - Paratracheal air cysts communicating with the trachea: CT findings.
AB  - We reviewed the chest radiographic and thin-section computed tomography (CT)
      findings in three adult patients with air-filled paratracheal cysts communicating
      with the tracheal lumen. The air collections were located on the right side in
      each case. On plain radiographs, they appeared round or oval and were 1-2 cm in
      diameter. On CT scans, they appeared irregular with a small communication between
      the tracheal lumen and the cyst. Thin-section and three-dimensional reconstructed
      CT were useful in detecting the communication between the trachea and
      paratracheal cyst. In one case, the communication was recognized at surgical
      resection and in the other two cases, the orifice in the tracheal wall appeared
      as a tiny, well-circumscribed hole at fiberoptic bronchoscopy.

PMID- 8989758
TI  - Tuberculosis in cancer patients: an update.
AB  - The demographics of tuberculosis (TB) and the therapy of malignancies have
      significantly changed since the last comprehensive review of TB in cancer
      patients. Fifty-six patients with both TB and malignancy were identified from
      January 1989 through December 1994 in a population of 61,931 newly registered
      cancer patients. The frequency of TB in cancer patients was 90 per 100,000. TB
      was more frequent in foreign-born patients (p < 0.001) and in racial and ethnic
      minorities (p < 0.001) than in non-Hispanic whites. TB developed during therapy
      in 48%. TB was discovered synchronously with the malignancy in 30% and in 21%
      occurred > or = 18 months after therapy. Pulmonary TB occurred in 50 (89%)
      patients and extrapulmonary TB in nine (16%) (three had both). Chest radiographic
      findings did not suggest TB in 20%. TB was less frequent in lung cancer (p <
      0.001), head and neck cancer (p = 0.002), and solid hematologic malignancies (p <
      0.001) than it had been historically, but the frequency was unchanged in acute
      leukemia patients (p = 0.46). TB in cancer patients occurs at a nine times
      greater than in the general population. It is now most frequent in leukemia
      patients.

PMID- 8989759
TI  - Chest radiograph interpretation of Pneumocystis carinii pneumonia, bacterial
      pneumonia, and pulmonary tuberculosis in HIV-positive patients: accuracy,
      distinguishing features, and mimics.
AB  - The purpose of this study was to assess the accuracy of chest x-ray (CXR)
      interpretation in the diagnosis of pneumocystis carinii pneumonia (PCP),
      bacterial pneumonia (BP), and pulmonary tuberculosis (TB) in human
      immunodeficiency virus (HIV)-positive patients and to identify the frequency with
      which these infections mimic one another radiographically. The admitting CXRs of
      153 HIV-positive patients with laboratory proven BP (n = 71), PCP (n = 73), and
      TB (n = 9) and those of 10 HIV-positive patients with no active disease were
      reviewed retrospectively and independently by three radiologists who were blinded
      to clinical and laboratory data. Median percent accuracies were as follows: TB,
      84%; PCP, 75%; BP, 64%; and no active disease, 100%. Fifteen of 153 cases (9.8%)
      were shown to mimic other infections radiographically. A confident and accurate
      diagnosis can be made radiographically in the majority of cases of PCP, BP, and
      TB in HIV-positive patients at the time of hospitalization. In approximately 10%
      of cases, these infections may mimic one another radiographically.

PMID- 8989760
TI  - Evaluation of the reliability of computed tomographic criteria used in the
      diagnosis of round atelectasis.
AB  - The purpose of this controlled study was to determine the diagnostic accuracy of
      computed tomography (CT) in the diagnosis of round atelectasis (RA). We reviewed
      two groups of chest CT scans of 22 patients (with 24 masses). Group 1 scans
      represent 10 patients (12 masses) known to have RA, and Group 2 scans represent
      12 patients with "RA look-alike" masses. Scans in both groups were selected for
      review by two of the authors and later independently reviewed by the other
      authors, who were blind to the actual diagnosis. Scans were rated for the
      presence/absence of 18 features ascribed to RA in the literature and assigned a
      percent probability of RA by each rater. Consensus was achieved for discordant
      ratings, and the individual percent probabilities were averaged to create a
      consensus probability. ROC curve analysis of the consensus percent probability
      showed that diagnostic accuracy significantly exceeded chance [area under curve
      (AUC) = 0.95, p < 0.001]. Of all the features of RA examined, the presence of
      converging bronchovascular markings discriminated best between RA and "RA look
      alikes" (sensitivity 83%, specificity 92%, likelihood ratio 11). Presence of
      adjacent pleural thickening and pleural-based location were even more sensitive
      features of RA (100% each), but lacked specificity (33 and 67%, respectively;
      likelihood ratios 3 and 1.5, respectively). We conclude that (a) although the
      diagnostic accuracy of CT for RA was high in this series, radiographic diagnosis
      is imperfect and that (b) the presence of converging bronchovascular markings was
      the best discriminator between the two groups, but that no single CT feature
      permitted perfect discrimination.

PMID- 8989761
TI  - Bronchoarterial inversion: radiographic-CT correlation in combined right middle
      and lower lobe collapse.
AB  - Pulmonary arteries of the right middle (RML) and right lower (RLL) lobes lie
      toward the lung periphery relative to their corresponding bronchi, i.e., along
      their lateral or posterior aspects. In contrast, those of the right upper lobe
      (RUL) tend to be located along the medial or anterior aspect of the bronchi. We
      postulate that a reversal of the normal bronchoarterial relationship at the lung
      base may indicate combined RML and RLL collapse. We evaluated bronchoarterial
      relation by computed tomography (CT) and posteroanterior (PA) chest radiographs n
      patients with combined RML and RLL collapse. On PA chest radiographs, an inverse
      bronchoarterial relationship could be recognized in the lower perihilar region in
      seven of 10 patients. In the 10 patients with complete collapse of both the RML
      and RLL, CT disclosed that the normal bronchoarterial relationship of the RUL was
      preserved, despite caudal extension of the RUL. In no case were arteries visible
      along the lateral aspect of bronchi. Thus, on frontal radiographs, when the
      bronchoarterial relationship in the right lower lung is inverse to that of normal
      subjects, combined collapse is strongly suggested.

PMID- 8989762
TI  - Azygos arch cannulation by central venous catheters: radiographic detection of
      malposition and subsequent complications.
AB  - The aim of this study was to determine the frequency of radiographically evident
      central venous catheter misplacement in the azygos arch and to analyze whether
      the frequency of azygos arch cannulation is dependent on the anatomical site of
      catheter insertion. We reviewed 1,287 postprocedural examinations and 3,441
      follow-up examinations. Catheters had been inserted through the left (6%) or
      right (15%) internal jugular veins and through the left (32%) or right (46%)
      subclavin veins. Radiographs were analyzed for possible catheter malposition in
      the azygos arch and for complications related to this malposition. Catheter
      malposition in the azygos arch was seen on 16/1,287 (1.2%) postprocedural
      radiographic examinations. Of the 16 malpositioned catheters, 11 (69%) had been
      inserted in the left subclavian vein, three (19%) in the left jugular vein, two
      (12%) in the right subclavian vein, and none (0%) in the right jugular vein.
      There was a statistically significant difference in the frequency of azygos arch
      cannulation between left- and right-sided catheters (p = 0.001). All
      complications consisted of venous perforations and were seen in three of 16 cases
      (19%). Azygos arch cannulation is a rare but hazardous central venous catheter
      malposition that occurs early after catheter insertion and carries a substantial
      risk for complication. The risk for azygos arch cannulation is substantially
      increased if catheters are inserted in left-sided veins. Because of the severity
      of subsequent complications, radiologists should be vigilant in the detection of
      this rare malposition.

PMID- 8989763
TI  - Fast gradient echo magnetic resonance imaging of the normal diaphragm.
AB  - To determine the ability of fast gradient-recalled echo (GRE), breath-hold
      magnetic resonance imaging (MRI) to depict all regions of the diaphragm, 13
      volunteers were scanned in coronal and sagittal planes. The central to anterior
      left hemidiaphragm and the posterior lumbar portions were each demonstrated in 12
      subjects (92%). The crura were visible crossing anterior to the aorta in the
      sagittal plane in eight subjects (62%) and in the coronal plane in six subjects
      (46%). In the sagittal plane, the right crus was evident in eight subjects (62%).
      Muscular portions of the diaphragm in contact with the liver or body wall were
      less frequently discernible, and the central tendon could not be confidently
      resolved. Several artifacts occurred that interfered with visualization of the
      diaphragm. These observations indicate that many regions of the diaphragm can be
      seen with fast GRE, breath-hold MRI, but there are some limitations in depicting
      the diaphragm in its entirety.

PMID- 8989764
TI  - Multicentric Castleman's disease and POEMS syndrome: CT findings.

PMID- 8989765
TI  - Sparing of some accessory lobes in diffuse pulmonary edema.
AB  - In patients with diffuse pulmonary edema we have noted a number who had sparing
      of accessory lobes. We postulate that this is due to a combination of two
      factors: diminished perfusion of the peripheral lung parenchyma and accessory
      fissures preventing interalveolar drift.

PMID- 8989766
TI  - Exocytosis from rat submandibular granular tubules during cyclocytidine
      stimulation shows unusual features, including changes in the granule membrane.
AB  - Sequential secretory changes in granular tubule cells caused by the secretagogue
      cyclocytidine (75 mg/kg i.p.) were studied at the ultrastructural level, in
      perfusion (n = 5 animals) and immersion (n = 8 animals) fixed rat submandibular
      glands, using the periodic acid-thiocarbohydrazide-silver proteinate technique
      (PA-TCH-SP). The onset of secretion varied from 45 to 75 minutes after
      administering the cyclocytidine. During the initial stages of overt secretion,
      structural changes occurred irregularly in a progressive fashion with: (1) an
      increase in granule membrane staining with PA-TCH-SP and a parallel alignment of
      the secretory granules with the adjacent apical plasma membrane, which developed
      a honeycomb-like appearance; (2) docking of these secretory granules to the
      apical plasma membrane; (3) early secretion of some secretory granules in a
      semiclassical exocytotic fashion (but this was rarely witnessed). During stages
      (1) and (2), the cytochemical characteristics of the membrane of the secretory
      granules, as well as of the plasma membrane, suggest a priming process is
      occurring. After these initial preparatory phases, further structural changes
      occurred in the granule membranes with a gradually progressive formation of
      microvesicles and granule fusions; secretion continued in an explosive manner
      with proteinaceous material being transferred to lumina in at least three
      different ways: (1) by typical exocytosis (but it was infrequent); (2) from
      granules fused intracellularly into aggregates (compound exocytosis); and (3)
      some apocrine-type of secretion through bleb formation. The formation of these
      intracellular aggregations was associated with the microvesicles in the granule
      membranes and some aggregates became very large. Secretion of their contents into
      lumina occurred through elongated membrane channels. The material secreted
      included microvesicular forms that had become interiorised in the granular
      aggregates, and any cytoplasm that may also have been entrapped.

PMID- 8989767
TI  - Time-variant analysis of organelle and vesicle movement during phagocytosis in
      Paramecium primaurelia by means of fluorescence confocal laser scanning
      microscopy.
AB  - Vital fluorescent dyes (FITC-albumin, Texas Red-albumin, and acridine orange)
      were used together with a confocal laser scanning optical microscope (CLSM) to
      display and analyze formation, movement, and fusion of vesicles during the
      phagocytosis of Paramecium primaurelia, in the x-y-z-t space. By immobilizing
      living cells pulsed with a food vacuole marker at successive times after chasing
      in unlabeled medium, the intracellular movement of food vacuoles from their
      formation at the cytostome to their egestion at the cytoproct was visualized, and
      food vacuoles were selected in a specific digestion stage. Small pinocytic
      vesicles are shown to evaginate from the vacuoles and move in the cytoplasm.
      These vesicles are transported toward the cytopharynx where they enlarge the
      membrane of the nascent food vacuoles or fuse with stage II food vacuoles, when
      the vacuoles of stage II increase their size, changing from an acidic to an
      alkaline status. A multimodal analysis of confocal fluorescence images and the
      false-color technique were used to visualize vesicle movement vs. time. Starting
      from three images of the same cell at succeeding time points, a composite image
      was generated by associating with each originally acquired image a different
      color corresponding to each sampling point in time. The composite image shows
      that vesicles move away from the food vacuole in a scattered manner exhibiting
      changes in direction.

PMID- 8989768
TI  - Comparison of high-pressure freezing/freeze substitution and chemical fixation of
      catfish barbel taste buds.
AB  - The barbel taste buds of catfish are widely used as a model system for
      investigating the structure and function of vertebrate taste buds. We have
      examined the ultrastructure of the taste buds of the channel catfish, Ictalurus
      punctatus, as part of a comparative study of the morphology of taste buds in
      various mammalian and non-mammalian vertebrates. Since conventional chemical
      fixation methods have limited usefulness for certain kinds of ultrastructural
      studies (i.e., localization of diffusible substances or labeling techniques
      requiring retention of biological activity), we have developed methods for fixing
      catfish barbel taste buds by high-pressure freezing followed by freeze
      substitution (HPF/FS) and have compared the ultrastructure of taste buds fixed by
      this technique and by chemical fixation procedures. The morphological details of
      the cells within taste buds are significantly affected by the method of fixation
      employed. In general, membrane contours are smoother and intracellular organelles
      more regular in shape in HPF/FS samples as compared with the chemically fixed
      specimens. Absolute and relative electron-densities of various tissue components
      are also affected by the fixation method employed. Certain ultrastructural
      features are more clearly visualized by one or the other of the fixation
      procedures. Fixation of barbel taste buds by HPF/FS not only provides an
      alternative view of the ultrastructure of taste bud cells but also offers a
      method of tissue preparation that may prove to be preferable to chemical methods
      for ultrastructural investigations involving procedures such as
      immunohistochemical labeling.

PMID- 8989769
TI  - Functional roles of neurotrophin 3 in the developing and mature sympathetic
      nervous system.
AB  - Nerve growth factor (NGF) is a potent regulator of sympathetic neuronal function
      in both developing and adult animals. This article reviews the evidence published
      in recent years indicating that another member of the NGF family, neurotrophin 3
      (NT3), plays both a complementary and overlapping role in the development and
      maturation of sympathetic neurons. In migratory neural crest cells, expression of
      the high-affinity receptor, trkC, and promotion of mitosis by NT3 suggest an
      involvement in gangliogenesis, since sympathetic neuroblasts express both NT3 and
      trkC and require NT3 for their proliferation, differentiation, and survival, it
      has been proposed that the factor acts at this developmental stage as an
      autocrine or paracrine factor. However, NT3 also acts in parallel with NGF to
      promote the survival of postmitotic neurons during late development. Both trkC
      and trkA are expressed in sympathetic neurons and function as high-affinity
      receptors for NT3. NT3 is synthesized in sympathetic effector tissues and the
      endogenous factor is retrogradely transported to accumulate within the cell soma.
      Thus, in addition to its role in the differentiation of sympathetic neurons, NT3,
      like NGF, is also an effector tissue-derived neurotrophic factor for these
      neurons in maturity.

PMID- 8989770
TI  - Single-cell analysis of gene expression in the nervous system. Measurements at
      the edge of chaos.
AB  - The characteristic functions of tissues and organs result from the integrated
      activity of individual cells. Nowhere is this more evident than in the nervous
      system, where the activities of single neurons communicating via electrical and
      chemical signals mediate complex functions, such as learning and memory. The past
      decade has seen an explosion in the identification of genes encoding proteins,
      such as voltage-gated channels and neurotransmitter receptors, responsible for
      neuronal excitability. These studies have highlighted the fact that even within a
      neuroanatomically defined region, the coexistence of multiple cell types makes it
      difficult, if not impossible, to correlate patterns of gene expression with
      function. The recent development of techniques sensitive enough to study gene
      expression at the single-cell level promises to break this bottleneck to our
      further understanding. Using examples taken from our own laboratories and the
      work of others, we review these techniques, their application, and discuss some
      of the difficulties associated with the interpretation of the data.

PMID- 8989771
TI  - Glucocorticoids and the hippocampus. Developmental interactions facilitating the
      expression of behavioral inhibition.
AB  - When threatened, the rapid induction of fear and anxiety responses is adaptive.
      This article summarizes the current knowledge of the neurobiological development
      of behavioral inhibition, a prominent response occurring in fear and anxiety
      provoking situations. In the rat, behavioral inhibition as exemplified by
      freezing first appears near the end of the second postnatal week. This emergence
      of freezing coincides with the developmental period marked by the rapid increase
      in plasma concentrations of glucocorticoids. Studies show that removal of
      glucocorticoids at this time severely impairs the age-dependent appearance of
      freezing. This behavioral impairment produced by adrenalectomy, however, is
      prevented by exogenous glucocorticoid administration. The effectiveness of
      glucocorticoids in facilitating the development of freezing appears to be caused
      by its actions in the hippocampus. In particular, glucocorticoids appear to play
      a vital role in the postnatal cellular development of the hippocampal dentate
      gyrus. Doses of glucocorticoids shown to reverse the behavioral inhibitory
      deficits occurring after adrenalectomy are ineffective when hippocampal dentate
      granule neurons are destroyed by neurotoxins. Notably, site-specific
      administration of glucocorticoids to the dorsal hippocampus is successful in
      promoting the occurrence of freezing in the adrenalectomized rat pup. It is
      hypothesized that glucocorticoids exert their behavioral inhibitory effects by
      influencing the development of the septohippocampal cholinergic system. Support
      for this hypothesis is derived from work demonstrating the importance of
      glucocorticoids on nerve growth factor systems that play a critical role in
      septohippocampal cholinergic survival.

PMID- 8989774
TI  - The genetic program of genital human papillomaviruses in infection and cancer.
AB  - Human papillomavirus (HPV) infection has been recognized as the major cause of
      cervical cancer. This article summarizes the functions of HPV gene products that
      cause abnormal cell growth--E6 and E7--and reviews how cellular and viral factors
      influence their synthesis. E6 and E7 inactivate two cellular tumor-suppressor
      gene products, p53 and RB. In cervical cancer, E6-E7 gene control is deranged by
      mutations in viral control sequences and in integrated HPV fragments by the
      disruption of the viral repressor E2. Elimination of this sequence makes E6-E7
      mRNAs unstable, and deranges cellular regulation at the integration site. It is
      apparent that an intricate interplay of cellular and viral factors determines
      whether the outcome is active papillomavirus infection, viral latency, or
      ultimately, genital cancer.

PMID- 8989775
TI  - Tissue effects and host response. The key to the rational triage of cervical
      neoplasia.
AB  - Genital HPV infections are associated with a spectrum of lesions ranging from
      benign condylomata to invasive cancer and its precursor lesions. The
      transformation zone of the cervix is the most frequent target of the high-risk
      HPV types. Depending on the nomenclature used, cancer precursors are subdivided
      on the basis of their morphologic presentation into dysplasias (mild, moderate,
      and severe); cervical intraepithelial neoplasias (CIN I, II, and III); or low
      grade and high-grade squamous intraepithelial lesions (LGSILs and HGSILs). The
      HGSILs (i.e., moderate and severe dysplasias, CIN II and III lesions) are
      recognized universally as cancer precursors. The LGSILs (i.e., very mild
      dysplasia and mild dysplasias, condylomata and CIN I lesions), have shown that
      one of the most important denominators of their cancer potential is the presence
      of intermediate and particularly high-risk HPV types. HPV typing provides the
      most rational basis for selecting women with LGSILs to be colposcoped and treated
      or given follow-up treatment with Pap smears. Until the clinical significance of
      HPV typing is known, management decisions may be based on an individual's risk
      factors such as age, compliance, past history of abnormal Pap smears, sexual
      habits, and access to adequate cytologic diagnosis.

PMID- 8989776
TI  - Clinical manifestations and natural history of genital human papillomavirus
      infections.
AB  - Over the past decade, the ever-increasing volume of evidence implicating HPV
      types in genital neoplasia has stimulated much research interest into all aspects
      of the biology of this interesting group of viruses. This research has led to the
      identification of growing heterogeneity of HPV types. It is not surprising,
      therefore, that the clinical profile of disease associated with genital HPV types
      is much broader than previously recognized. Knowledge of this clinical spectrum
      is mandatory to the understanding of the possible role of specific HPV types in
      human carcinogenesis.

PMID- 8989777
TI  - Clinical role of HPV testing.
AB  - The subjectivity of morphologic methods contributes to a "swamping" of
      colposcopic services, excessive costs, overdiagnosis, and overtreatment. HPV DNA
      testing provides the objectivity required to clarify difficult patient management
      issues, including follow-up, for low-grade cytologic abnormalities (ASCUS and
      LSIL), noncorrelating (nonconfirmed) Pap smears, evaluation of nondiagnostic
      lower genital tract lesions, and cytology and histology laboratory quality
      assurance. Additionally, favorable preliminary data on HPV testing as a primary
      screen raise the exciting prospect of potentially lowering costs of cervical
      cancer-screening programs, while further decreasing the incidence of cervical
      cancer.

PMID- 8989773
TI  - Thyroid parafollicular cells. An accessible model for the study of serotonergic
      neurons.
AB  - Serotonergic neurons play key roles in modulating a wide variety of behavioral
      and homeostatic processes. However, there is a paucity of good model systems to
      study these neurons at a molecular level. In this review we will present evidence
      that cell lines derived from an unexpected source, thyroid parafollicular cells
      (PF) (also called C cells), fit the criteria for use as models for the study of
      serotonergic neurons. A strength of PF cell lines over other cell lines is that
      the parental PF cells have serotonergic properties and a neuronal potential that
      is consistent with their neural crest origin. Furthermore, PF cells and PF cell
      lines are capable of expressing the fundamental properties of serotonergic
      neurons, including: (1) serotonin (5-HT) biosynthesis by tryptophan hydroxylase
      (TPH), (2) vesicular 5-HT storage and regulated release, (3) expression of a 5-HT
      autoreceptor, and (4) expression of the 5-HT transporter. In this review, we will
      focus primarily on the serotonergic and neuronal properties of the rat CA77 PF
      cell line and the parental rat PF cells. The applicability of CA77 cells for
      molecular analyses will be described. First, their use for studies on the
      glucocorticoid regulation of the TPH gene will be discussed. Second, control of
      the calcitonin/calcitonin gene-related peptide (CT/CGRP) gene will be discussed,
      with particular emphasis on the application of serotonergic drugs in treating
      migraine headaches. These examples highlight the versatility of thyroid PF cell
      lines as a system for studying the control of both serotonin biosynthesis and
      physiological actions.

PMID- 8989772
TI  - The role of the insulin-like growth factors in the central nervous system.
AB  - Increasing evidence strongly supports a role for insulin-like growth factor-I
      (IGF-I) in central nervous system (CNS) development. IGF-I, IGF-II, the type IIGF
      receptor (the cell surface tyrosine kinase receptor that mediates IGF signals),
      and some IGF binding proteins (IGFBPs; secreted proteins that modulate IGF
      actions) are expressed in many regions of the CNS beginning in utero. The
      expression pattern of IGF system proteins during brain growth suggests highly
      regulated and developmentally timed IGF actions on specific neural cell
      populations. IGF-I expression is predominantly in neurons and, in many brain
      regions, peaks in a fashion temporally coincident with periods in development
      when neuron progenitor proliferation and/or neuritic outgrowth occurs. In
      contrast, IGF-II expression is confined mainly to cells of mesenchymal and neural
      crest origin. While expression of type I IGF receptors appears ubiquitous, that
      of IGFBPs is characterized by regional and developmental specificity, and often
      occurs coordinately with peaks of IGF expression. In vitro IGF-I has been shown
      to stimulate the proliferation of neuron progenitors and/or the survival of
      neurons and oligodendrocytes, and in some cultured neurons, to stimulate
      function. Transgenic (Tg) mice that overexpress IGF-I in the brain exhibit
      postnatal brain overgrowth without anatomic abnormality (20-85% increases in
      weight, depending on the magnitude of expression). In contrast, Tg mice that
      exhibit ectopic brain expression of IGFBP-1, an inhibitor of IGF action when
      present in molar excess, manifest postnatal brain growth retardation, and mice
      with ablated IGF-I gene expression, accomplished by homologous recombination,
      have brains that are 60% of normal size as adults. Taken together, these in vivo
      studies indicate that IGF-I can influence the development of most, if not all,
      brain regions, and suggest that the cerebral cortex and cerebellum are especially
      sensitive to IGF-I actions. IGF-I's growth-promoting in vivo actions result from
      its capacity to increase neuron number, at least in certain populations, and from
      its potent stimulation of myelination. These IGF-I actions, taken together with
      its neuroprotective effects following CNS and peripheral nerve injury, suggest
      that it may be of therapeutic benefit in a wide variety of disorders affecting
      the nervous system.

PMID- 8989778
TI  - Prospects for automated cytology.
AB  - Rescreening of Pap smears using automated devices offers the ability to re
      examine Paps initially interpreted as within normal limits and to use cell
      sorting technology to increase the detection of missed abnormal smears. Only
      recently has the development of high-resolution imaging techniques and advances
      in computer sciences and cell classifiers enabled investigators to achieve
      sensitivity and specificity levels in automated screening and quality control
      devices.

PMID- 8989779
TI  - Anogenital papillomavirus infection and neoplasia in immunodeficient women.
AB  - This article reviews the impact of infection with human immunodeficiency virus
      (HIV) on HPV infections and HPV-associated lesions of the female anogenital
      tract. Studies investigating HPV infections in HIV-seropositive women are
      presented as well as the possibility that HIV can influence HPV expression
      directly through molecular interactions between viral genes and indirectly
      through immunosuppression. Studies linking HIV infection to invasive cervical
      cancer and cervical intraepithelial neoplasia are reviewed; recommended protocols
      for cervical cancer screening in HIV-seropositive women for cervical disease also
      are presented.

PMID- 8989781
TI  - The management of genital condylomas, intraepithelial neoplasia, and vulvodynia.
AB  - The natural history of HPV-related disease still is poorly understood. Screening
      of apparently healthy populations suggests that most HPV exposure results only in
      latent infection; that is, there is no active HPV DNA replication, but the HPV
      copy number is held at a steady state because viral replication parallels cell
      division. Unfortunately, knowledge of the cell-virus interaction and the host
      immune response has not yet provided an effective medical therapy or a preventive
      vaccine. Rather, the management of HPV-induced disease remains rooted to the
      strategy of repeated local destruction. The physician should work methodically
      through a series of strategic decisions before committing to a management plan.

PMID- 8989780
TI  - HPV infection and disease in men.
AB  - Penile HPV infection and disease are very common in sexually active men, and may
      be manifest in many forms. Treatment of clinically detectable lesions is
      advisable not only to relieve symptoms but also to prevent the spread of HPV
      infection to new sexual partners. Treatment of subclinical disease is more
      controversial but also may be advisable in some cases given the evidence that
      these lesions may also harbor infectious virus. In addition, subclinical disease
      may demonstrate intraepithelial neoplasia, which if left untreated may progress
      to invasive cancer in a small number of cases. Anal HPV infection and ASIL are
      very common in high-risk homosexual and bisexual men, particularly among those
      who are HIV positive. Parallels with cervical HPV infection and disease suggest
      that anal HSIL may be precancerous, and indeed anal cancer may be as common or
      more common in this high-risk group as cervical cancer is in women. Further
      studies are needed to elucidate the natural history of ASIL, the role of
      immunosuppression in progression to invasive cancer, optimal diagnostic methods,
      and optimal treatment regimens. Like cervical cancer, anal cancer may be a
      preventable disease, and implementation of a well-targeted screening program
      similar to that in place for cervical disease should be considered in the future
      when appropriate supporting data become available.

PMID- 8989782
TI  - The increasing burden of pediatric firearm injuries on the emergency department.
AB  - INTRODUCTION: Surveillance of injuries is necessary in order to develop
      preventive strategies. The purpose of this study was to examine pediatric gunshot
      wounds over a seven-year period for changes in frequency, site of injury, and
      demographic variables. METHODS: The medical charts of all pediatric patients (age
      < 19 years) who presented to the two urban emergency departments (EDs) in Baton
      Rouge, Louisiana between January 1, 1987, and December 31, 1993, were
      retrospectively reviewed. Data included age, date and time of presentation,
      site(s) of injury, disposition, operative procedure, and hospital stay. Results
      were stratified into age < 1 year, 1-4 years, 5-9 years, 10-14 years, and 15-19
      years. RESULTS: During the study period there were 465 pediatric firearm injuries
      seen in the two urban EDs. Of all patients, 302 (65%) were male, and the
      proportion remained unchanged during the study period. The incidence of firearm
      injury rose from 3.0/1000 pediatric ED patients in 1987 and 5.9 in 1993 (P <
      0.05). Mean age rose from 12.2 +/- 2.1 years to 15.1 +/- 1.6 years (P < 0.05),
      and admission percentage rose from 7 to 46% (P < 0.05) between 1987 and 1993. The
      proportion of firearm injuries in the age group 15 to 19 years rose from 52% in
      1987 and 82% in 1993 (P < 0.05). Operative procedures were required by 56 (12%)
      and intensive care admission by nine (2%); this did not change significantly over
      the study period. Thirty-three (7%) of all victims died. The most common sites of
      injury in decreasing order of frequency were extremity (60%), head/neck (14%),
      chest/back (13%), abdomen/flank (7%), and pelvis/buttocks (6%); they did not vary
      by age group. A significantly greater proportion of pediatric firearm injuries
      presented between 5 PM and 5 AM (65%), on Friday (24%) or Sunday (20%), and
      during the three summer months (29%) or December (11%). CONCLUSIONS: The
      frequency of pediatric gunshot wounds presenting to urban EDs has increased
      significantly since 1987. These findings confirm previous studies concerning site
      of injury as well as time, date, and month of presentation and suggest targeting
      preventative measures at the 15- to 19-year age group.

PMID- 8989783
TI  - The need for pediatric-specific triage criteria: results from the Florida Trauma
      Triage Study.
AB  - OBJECTIVE: The objective of the Florida Trauma Triage Study was to assess the
      performance of state-adopted field triage criteria. The study addressed three
      specific age groups: pediatric (age < 15 years), adult (age 15-54 years), and
      geriatric (age 55+ years). Since 1990, Florida has used a uniform set of eight
      triage criteria, known as the trauma scorecard, for triaging adult trauma
      patients to state-approved trauma centers. However, only five of the criteria are
      recommended for use with pediatric patients. This article presents the findings
      regarding the performance of the scorecard when applied to a pediatric
      population. DESIGN: We used state trauma registry data linked to state hospital
      discharge data in a retrospective analysis of trauma patients transported by
      prehospital providers to any acute care hospital within nine selected Florida
      counties between July 1, 1991, and December 31, 1991. We used cross-table and
      logistic regression analysis to determine the ability of triage criteria to
      correctly identify patients who were retrospectively defined as major trauma. We
      applied the field criteria to physiologic and anatomy/mechanism of injury data
      contained in the trauma registry to "score" the patient as major or minor trauma.
      To make our retrospective determination of major or minor trauma we used the
      protocols developed by an expert medical panel as described by E. J. MacKenzie et
      al. (1990). MAIN OUTCOME MEASURES: We calculated sensitivity, specificity, and
      the corresponding over- and undertriage rates by comparing patient
      classifications (major or minor trauma) produced by the triage criteria and the
      retrospective algorithm. We used logistic regression to identify which triage
      criteria were statistically significant in predicting major trauma. RESULTS:
      Pediatric cases accounted for 9.2% of the total study population, 6.0% of all
      hospitalized cases, and 6.8% of all trauma deaths. Of the 1505 pediatric cases
      available for analysis, the triage criteria classified 269 cases as expected
      major trauma and 1236 cases as expected minor trauma. The retrospective algorithm
      classified 78 cases as expected major trauma and 1427 cases as expected minor
      trauma. The resulting specificity is 84.8% (15.2% overtriage), and the
      sensitivity is 66.7% (33.3% undertriage). Logistic regression indicated that, of
      the eight state-adopted field triage criteria, only the Glasgow coma score,
      ejection from vehicle, and penetrating injuries have a statistically significant
      impact on predicting major trauma in pediatric patients. CONCLUSIONS: Although
      the state-adopted trauma scorecard, applied to a pediatric population, produced
      acceptable overtriage, it did not produce acceptable undertriage. However, our
      undertriage rate is comparable to the results of other published studies on
      pediatric trauma. As a result of the Florida Trauma Triage Study, a new pediatric
      triage instrument was developed. It is currently being field-tested.

PMID- 8989784
TI  - Physician parents and utilization of a pediatric emergency department.
AB  - OBJECTIVE: Health care costs might be reduced if patients could be taught to
      avoid using an emergency department (ED) for nonurgent illness. This study sought
      to determine whether children with a physician parent, a group whose parents
      possess special expertise in judging the severity of acute illness, utilize a
      pediatric ED differently from children with non-physician parents. DESIGN:
      Retrospective cohort study. SETTING: A children's hospital ED. PARTICIPANTS: The
      study population consisted of all children who visited the ED over an 11-month
      period who had a physician parent. These children were compared to 1000 controls
      randomly selected from children who visited the ED over the same time period. Two
      other groups were selected for comparison to controls: children with a nurse
      parent and children with an attorney parent. MAIN OUTCOME MEASURES: Urgent versus
      nonurgent final diagnosis. RESULTS: There were no clinically important or
      statistically significant differences with regard to age, sex, time of
      presentation, disposition from the ED, or nursing acuity level when the 72
      children with a physician parent, the 136 children with a nurse parent, or the
      135 children with an attorney parent were compared to the control children.
      Compared to the control group, children of physician parents were less likely to
      have a nonurgent final diagnosis: 33 versus 53%; relative risk (RR) 0.62 (95%
      confidence interval [CI] 0.44-0.87). Children with a nurse parent and children
      with an attorney parent were no more likely to present with a nonurgent diagnosis
      compared to control children: 49 versus 53%, RR 0.92 (95% CI 0.76-1.10) for
      children with a nurse parent and 45 versus 53%, RR 0.85 (95% CI 0.70-1.03) for
      children with an attorney parent. CONCLUSIONS: Children with a physician parent
      were less likely to use a pediatric ED for nonurgent problems compared to other
      children. However, children with a nurse parent, a group whose parents have more
      medical education than we can expect the general public to ever attain, had a
      pattern of pediatric ED utilization that was similar to the control children.
      These data suggest that improved parental education alone may not decrease ED use
      for conditions that could be managed in a less costly setting.

PMID- 8989785
TI  - Intravenous regional anesthesia for management of children's extremity fractures
      in the emergency department.
AB  - OBJECTIVE: To determine if intravenous regional anesthesia (Bier block) is safe
      and efficacious for the management of children's extremity fractures in the
      emergency department (ED). DESIGN: Retrospective review of 470 ED records of
      children presenting with extremity fractures reduced with intravenous regional
      anesthesia from 1989 through 1994. SETTING: ED of a 256-bed teriary care
      children's hospital. PATIENTS: Four hundred seventy children treated in the ED
      from 1989 through 1994 for extremity fractures reduced with Bier block
      anesthesia. Three hundred eleven boys and 159 girls with a mean age of 9.4 years
      (range two-19 years) were included in the review. INTERVENTION: Utilization of
      intravenous regional anesthesia for fracture reduction of affected extremity.
      MAIN OUTCOME MEASURES: ED records and orthopaedic consultation notes were
      reviewed for adequacy of reduction, number of reduction attempts, efficacy of
      anesthesia, and any associated untoward effects or complications, and review of
      operative notes of any children who required a subsequent procedure in the
      operating room (OR) under general anesthesia. RESULTS: Ninety-nine percent (467)
      had adequate anesthesia for fracture reduction. There were no complications
      noted. Specifically, there were no incidents of hypotension, tachycardia,
      seizures, or arrhythmia. Bier block anesthesia was aborted in three patients
      because venous access could not be obtained in the affected extremity. Less than
      2% (8) required a general anesthetic in the OR for further treatment. All of the
      children taken to the OR underwent internal fixation of the fracture.
      CONCLUSIONS: Intravenous regional anesthesia (Bier block) is safe and efficacious
      in the treatment of children's extremity fractures in the ED.

PMID- 8989786
TI  - Evaluating the effectiveness of a pediatric trauma educational program in Central
      America.
AB  - OBJECTIVE: To evaluate the effectiveness of a pediatric trauma course taught in a
      developing country. STUDY DESIGN: A pediatric trauma course was designed with
      didactic presentations and reinforced with small group case discussions. Subjects
      included a general trauma overview, head trauma, airway/chest trauma, cervical
      spine trauma, abdominal trauma, shock, burns, and orthopedic injuries. Evaluation
      consisted of a pre- and post-course test and questionnaire assessing the
      participants' knowledge and level of comfort in managing trauma. Nine months
      after the course, the participants were evaluated with the same post-course test.
      Also a questionnaire was given to physician and nurse co-workers from the
      participating institutions, who themselves had not participated in the course, to
      assess the perceptual and attitudinal impact of the pediatric trauma course.
      SETTING: Guatemala City, Guatemala. PARTICIPANTS: Forty-three physicians from
      Central America. RESULTS: Initial and nine-month post-test scores showed uniform
      improvement (P value < 0.05) when compared to pretest results using the Wilcoxon
      signed-ranks test. Analysis of the pre- and post-course questionnaires indicated
      that all participants felt more comfortable (scale 1 to 5) after the course
      managing pediatric trauma patients. All participants "strongly agreed" the course
      provided information that would improve their management of the pediatric trauma
      victim. Nine months after the course, 100% of their medical co-workers perceived
      physicians who participated in the pediatric trauma course to have better
      resuscitative skills, and 92% perceived these physicians to have a higher level
      of confidence. CONCLUSION: This course, when presented to physicians in a
      developing country, appears to be effective in improving their knowledge base
      regarding pediatric trauma and increasing their comfort level in managing major
      pediatric trauma.

PMID- 8989788
TI  - Factors associated with prolongation of transport times of emergency pediatric
      patients requiring transfer to a tertiary care center.
AB  - PURPOSE: The purpose of this study was to determine factors associated with
      longer times to transport of emergency pediatric patients requiring tertiary
      care. DESIGN: Retrospective case series. SETTING: Emergency pediatric transport
      service. PARTICIPANTS: Infants and children transported by the transport service
      at the University of North Carolina Hospitals at Chapel Hill from January 1,
      1988, to December 31, 1990. MAIN MEASUREMENTS: The time-to-request, the time from
      patient arrival at the referring hospital to the time when the request for
      transfer was received, and the ground time, defined as the time between the
      transport team's arrival at the referring hospital and their departure, were
      recorded for each transported patient. RESULTS: Three hundred consecutive
      children 0 to 16 years (61% male) were transferred. Time-to-request was shorter
      for trauma patients (median 62 minutes, quartiles 29 and 153 minutes) than for
      medical patients (median 172 minutes, quartiles 83 and 508 minutes) (P = 0.0001).
      Infants, children, and adolescents had similar times-to-request of 147 minutes,
      129 minutes, and 128 minutes, respectively (P = 0.91). Increased ground times
      were associated with diagnosis category (median of 40 minutes for medical
      patients vs 29 minutes for trauma patients) (P = 0.0001), with younger age
      (median of 46 minutes for infants, 35 minutes for children, and 28 minutes for
      adolescents) (P = 0.0001), and with the performance of major procedures (median
      of 35 minutes if no procedures were performed, 38 minutes if one procedure was
      performed, and 54 minutes if two procedures were performed) (P = 0.039). After
      the transport team arrived, 13% (40/300) of patients required at least one major
      procedure prior to transport. CONCLUSIONS: Increased time-to-request for patients
      with medical diagnoses, increased ground times for younger patients and patients
      with medical diagnoses, and failure to perform necessary procedures contribute to
      a prolongation of the time-to-transport of emergency pediatric patients. The
      magnitude of the impact of these longer transport times on outcome is unknown.

PMID- 8989787
TI  - Pediatric injuries presenting to an emergency department in a developing country.
AB  - PURPOSE: To describe the causes and outcomes of pediatric injuries using the
      emergency departments (ED) as a surveillance site. METHOD: Prospective, 14-day
      surveys of all injuries were conducted in the EDs of the two national trauma
      referral hospitals of Trinidad and Tobago. Data on patient demographics, type,
      cause, and outcome of injuries were collected. The chi 2 test for significance
      was used for categorical variables. RESULTS: Pediatric patients (< 20 years)
      accounted for 41.5% (714/1722) of injury visits. Of these, 62.6% were male and
      17.4% were < four years old, 26.2% four to nine years, 31.1% 10 to 14 years, and
      25.4% were 15 to 19 years old. Three patients (0.4%) died, 68.6% were discharged,
      and 31.0% admitted. Intentional injuries accounted for 13.9% of injuries. Of the
      intentional injuries, the assailant was significantly more likely to be known
      than not (P < 0.01). The most common causes of all injuries were: falls, 44.4%;
      blunt objects, 12.3%; sharp objects, 11.8%; motor vehicle (including
      pedestrians), 7.4%; poison, 3.6%; and burns, 1.7%. Injuries occurring in the home
      accounted for 46.2%; in school, 25.5%; sports/recreation, 11.1%; and at work,
      4.5%. The most common injuries were: lacerations, 30.8%, contusions/abrasions,
      26.7%, fractures, 18.8%; and sprains/dislocations, 9.4%. CONCLUSION: Pediatric
      injuries are a significant cause of morbidity and mortality in this country,
      accounting for almost one third of injured patients. Because of the low frequency
      of pediatric injury deaths, ED surveillance may be a more effective means of
      identifying high risk groups and activities for injuries. Data from EDs may be
      useful in other developing countries to develop injury prevention programs.

PMID- 8989789
TI  - A child with cardiogenic shock and supraventricular tachycardia presenting in
      normal sinus rhythm.
AB  - We report a case of an infant who presented in profound cardiovascular collapse
      with a normal sinus rhythm initially. A diagnosis of supraventricular tachycardia
      (SVT) was established only after hemodynamic stabilization. The possibility of
      SVT being masked because of severe metabolic derangements and/or painful
      therapeutic procedures should be kept in mind when managing cardiogenic shock in
      children. Such a consideration is of practical significance in planning therapy,
      such as the avoidance of digitalis in a patient with Wolf-Parkinson-White
      syndrome.

PMID- 8989790
TI  - A deep-tissue hemangioma presenting as a rapidly progressive expanding mass and
      thrombocytopenia in an infant.
AB  - OBJECTIVE: We present a case of Kasabach-Merritt syndrome with discussion of
      hemangiomas of childhood relevant to the emergency physician. DESIGN: This is a
      case report. SETTING: The case is described in the setting of a tertiary care
      hospital level I pediatric emergency department. PATIENTS: A single case is
      discussed. INTERVENTIONS: The patient's condition was diagnosed and referred to
      the appropriate hematology service. Methylprednisolone (2 mg/kg/day) therapy was
      instituted. CONCLUSIONS: Children may present to the emergency department with a
      mass requiring diagnosis. The emergency physician must efficiently and
      economically identify the cause and complications from a variety of etiologies.
      Hemangiomas with complicating thrombocytopenia and microangiopathic hemolysis are
      rare and must be correctly identified. The emergency physician should
      occasionally review such unusual diagnoses to maintain their differential
      diagnosis skills.

PMID- 8989792
TI  - Accidental penetrating cervical cord injury in a young child.
AB  - A three-year-old child presented to our emergency department with a hemiparesis
      five days following the accidental laceration of her neck with a piece of glass.
      The laceration had been thought to be superficial when she was initially
      evaluated. When seen again three days following the injury because of right-sided
      weakness, computerized tomography of her head and neck was unrevealing. However,
      using high resolution magnetic resonance imaging (MRI) we were able to
      demonstrate a C1-2 cord contusion and an injury tract leading from the surface of
      the neck to this site. The unusual mechanism of injury and the underlying
      pathophysiology of this patient's presentation are reviewed. It is important for
      the emergency physician to be reminded that what appears to be a superficial
      laceration can sometimes be more serious. MRI should be considered in the
      evaluation of patients who have suffered penetrating trauma if the potential for
      spinal cord injury exists and especially when there are signs or symptoms
      suggesting spinal cord dysfunction.

PMID- 8989791
TI  - Severe eclampsia in an adolescent: a case report and review of the literature.
AB  - We present this interesting case of an adolescent female with seizures and a
      history of a fall, who was found to be pregnant and eclamptic, requiring emergent
      delivery on the day of presentation to a pediatric emergency department. The
      relevant literature is reviewed.

PMID- 8989793
TI  - Fatal extradural hemorrhage following a fall from a baby bouncer.
AB  - Prevention of infant deaths from accidental falls from baby equipment requires
      the maintaining of safety standards and adequate supervision of the infant. Mason
      in 1989 stated that those under one year old are usually injured because they are
      left unattended in, for example, bouncing cradles or baby walkers. Severe
      accidental head injury is relatively uncommon in children under two years of age,
      and in those patients less than one year of age, accidental injury is 10 to 15
      times more common than nonaccidental injury. Gallagher et al. state that falls
      are the most common cause of accidental injury to the head in children under two
      years of age (mainly on stairs), whereas falls in older children tend to cause
      limb injuries. Both falls and burns are well documented with regard to the baby
      walker, but the author has found no reference to injuries from baby bouncers.
      This case proves that it is not necessary for a child to fall from a great height
      to sustain a life-threatening head injury. This infant's head was only about two
      feet from the ground, and he landed on a thick carpet. Pivoting about the central
      point provided by the seat of the bouncer obviously increased the momentum of the
      head before it struck the ground and so the injury was more severe than a
      straightforward fall back from his own height to the ground. However, it is
      important to be aware that serious head injuries can result from apparently minor
      falls. It is hoped that this case will highlight the dangers that do exist when
      using the baby bouncer, especially if the equipment is worn and adult supervision
      is absent.

PMID- 8989794
TI  - Sedation and analgesia for minor pediatric procedures.
AB  - Owing to recent emphasis upon the benefits of effective pain management, parents
      and health care providers expect infants and children to receive safe, effective
      sedation and analgesia for diagnostic and therapeutic procedures. The Committee
      on Drugs of the American Academy of Pediatrics has addressed the issue of safety
      in its recently revised guidelines for monitoring and management of patients
      undergoing sedation for procedures. Patients undergoing emergency procedures
      present additional problems because of the limited opportunity to optimally
      prepare patients and families. Today, managing children undergoing invasive
      procedures can include the use of sedatives, analgesics, anesthetics, and
      nonpharmacologic strategies. New formulations of local and topical anesthetics
      have enhanced their efficacy and reduced pain associated with administration.
      Innovations in the administration of sedatives and analgesics, as well as
      antagonists, have enhanced both efficacy and safety. This article reviews
      recommended guidelines for monitoring and management of patients undergoing
      sedation for minor procedures and discusses various sedative, analgesic, and
      anesthetic alternatives available to clinicians.

PMID- 8989795
TI  - Electronic, automatic sphygmomanometers.

PMID- 8989796
TI  - Hip pain after twisting leg.

PMID- 8989797
TI  - Pediatric emergency medicine: legal briefs.

PMID- 8989798
TI  - HMO confrontations.

PMID- 8989799
TI  - Guidelines for pediatric equipment and supplies for basic and advanced life
      support ambulances. Committee on Ambulance Equipment and Supplies, National EMSC
      Resource Alliance.

PMID- 8989800
TI  - Oncology and transport. Beware of the presentation and anticipate the clinical
      course.
AB  - These cases demonstrate a few of the presentations that may occur with new onset
      oncologic problems. While the transport phase of these children's care was not
      extraordinary, the development and management of the clinical issues might have
      been influenced by earlier interventions. Would the outcome of Case 1 have been
      different if the abnormal hematologic parameters demonstrated on the preoperative
      laboratory results had been further investigated? Would the institution of
      cerebral resuscitative measures before and during transport have offered this
      child a better chance of survival? Would the involvement of a specialized
      pediatric team earlier in the process have addressed some of those issues and
      would it have made a difference? Should the patient in case two have had cerebral
      resuscitative measures instituted at the referring hospital or during transport?
      In hindsight, this clearly would not have been useful or beneficial to the
      patient. But what if the initial CT interpretation of a brain tumor and increased
      intracranial pressure with ventricular ablation and midline shift had been
      correct? Should the transport team have suggested or instituted a different level
      of therapy with the information that was available at the time of transport? The
      patient in Case 3 had a dramatic presentation of his ALL. Were there signs and
      symptoms that should have alerted the referring hospital, transport command
      physician or transport team to the likely deterioration of that patient? If this
      patient had presented to a hospital a further distance away, would the impending
      cardiovascular collapse and respiratory failure have been anticipated or occurred
      during the transport? Would or should the mode of transport or team configuration
      have been altered? If this patient had deteriorated during the transport, would
      the transport team have had the skills to manage this potentially difficult
      airway? Should the patient in Case 4 have had antihypertensive medication started
      at the referring hospital or during the transport process? What are the
      guidelines for antihypertensive intervention in this situation? If
      antihypertensive therapy were instituted by the transport team, should this have
      affected time or mode of transport, or was it more prudent not to rock the boat
      by instituting interventional therapy? Is hypertension a different issue with a
      liver mass, as suspected at the time of referral, or with a nephrogenic tumor?
      These cases afford us the ability to review several presentations of oncologic
      emergencies. The questions above are but a few of the potential areas of
      discussion that can arise from these cases. We should use these cases as an
      opportunity to review and refresh our transport teams on the many faces of
      oncology and potential pitfalls in the care of those patients.

PMID- 8989801
TI  - Better parent instruction on the use of the otic thermometers.

PMID- 8989802
TI  - Management of children at risk for occult bacteremia.

PMID- 8989803
TI  - Epidemiology of chronic arthritis in childhood.
AB  - This study was performed to review reports of the descriptive epidemiology of
      chronic arthritis in childhood and to analyze the factors that may explain
      differences in its reported frequency. Articles were retrieved by searching
      MEDLINE and EMBASE under the following index terms: juvenile rheumatoid arthritis
      (JRA), juvenile chronic arthritis (JCA), spondyloarthropathy, epidemiology,
      prevalence, and incidence. For reports published between 1977 to 1982, the Index
      Medicus was used. All original articles that provided prevalence or incidence
      rates, population size, or number of cases, were reviewed and entered into the
      analysis. Variables analyzed were disease prevalence and incidence. Modifier
      variables investigated were diagnostic criteria, source population, geographic
      origin of the report (Europe or North America), duration of the study, and race
      of the population studied. Diagnostic criteria had no effect on reported
      prevalence or incidence rates. Prevalence per 100,000 at risk obtained from
      population studies (132, 95% CI: 119, 145) was significantly higher than values
      derived from practitioner- (26, 95% CI: 23, 29) or clinic-based studies (12, 95%
      CI: 10, 15) (P = .02). North American clinic-based studies had higher prevalence
      values compared with European reports (32, 95% CI: 26, 38 versus 8, 95% CI: 5,
      11, P = .009). None of the factors analyzed accounted for the variability in
      reported incidence rates. An effect of race was detected only in the distribution
      of patients among onset subsets. Thus, the percentage of patients with
      pauciarticular JRA was highest in series of North American and European caucasian
      patients (58, 95% CI: 56, 60) compared with series of East Indian (25, 95% CI:
      20, 31), native North American Indian (26, 95% CI: 15, 37), or other races (31,
      95% CI: 28, 35) (P = .001). In contrast, the percentage of patients with
      polyarticular JRA was lowest in the former (27, 95% CI: 25, 28) compared with the
      other racial groups (East Indian, 61, 95% CI: 55, 66; native North American
      Indian, 64, 95% CI: 53, 76; other races, 34, 95% CI: 30, 38) (P = .004). Although
      an effect of source population on reported prevalence was confirmed, the effect
      of geographic origin suggests that environmental or ethnic differences also may
      influence the prevalence of chronic arthritis in children. Differences in the
      percentages of patients with pauciarticular and polyarticular JRA may reflect
      racial differences in the prevalence of these conditions.

PMID- 8989804
TI  - Septic sacroiliitis.
AB  - Two cases of septic sacroiliac (SI) joint arthritis are presented to illustrate
      the difficulty of diagnosing and treating this uncommon osteoarticular infection.
      The patients presented are a 68-year-old woman with septic sacroiliitis caused by
      Streptococcus agalactiae and a 20-year-old man with Salmonella infantis infection
      involving the SI joint. The recent literature is reviewed and compared with
      previously published series. Of the 177 cases we reviewed, 47 (27%) occurred in
      pediatric patients. The mean age was 20 years. Only six patients (3%) were older
      than 60 years of age. Magnetic resonance imaging (MRI) is most useful for
      defining extent of infection, osteomyelitis, and abscess formation in the SI
      joint. Computed tomography (CT) is valuable for defining the extent of bone
      involvement and for guidance of percutaneous needle arthrocentesis. Other imaging
      modalities are useful primarily in the initial evaluation of patients with a
      nonspecific presentation. Four to six weeks of intravenous (i.v.) antibiotic
      therapy is recommended. Indications for surgical intervention include abscess
      formation, osteomyelitis, sequestrum of necrotic bone, and failure to respond to
      i.v. antibiotic therapy.

PMID- 8989805
TI  - Familial aggregation in the fibromyalgia syndrome.
AB  - The authors studied the familial occurrence of fibromyalgia (FMS) to determine a
      possible role of genetic and familial factors in this syndrome. Fifty-eight
      offspring aged 5 to 46 years (35 males and 23 females) from 20 complete nuclear
      families ascertained through affected mothers with FMS were clinically evaluated
      for FMS according to the ACR 1990 diagnostic criteria. FMS symptoms, quality of
      life, physical functioning, and dolorimetry thresholds were assessed in all
      subjects. Sixteen offspring (28%) were found to have FMS. The M/F ratio among the
      affected was 0.8 compared with 1.5 in the whole study group. Offspring with and
      without FMS did not differ on anxiety, depression, global well-being, quality of
      life, and physical functioning. A high prevalence of FMS was observed among
      offspring of FMS mothers. Because psychological and familial factors were not
      different in children with and without FMS, the high familial occurrence of this
      syndrome may be attributable to genetic factors.

PMID- 8989806
TI  - The changing face of familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is a genetic disease characterized by painful
      febrile "attacks" of serositis and the development of amyloidosis. Although FMF
      has been extensively studied and described, new data have accumulated during the
      last decade. This report gives an update, focusing specifically on (1) newly
      characterized manifestations, such as acute scrotal "attacks," protracted febrile
      myalgia, and spondyloarthropathy; (2) progress made in the diagnosis and
      treatment of FMF-amyloidosis; (3) experience acquired with colchicine,
      establishing its safety in common practice, childhood, conception, and pregnancy;
      (4) colchicine's role in the prevention and treatment of FMF-amyloidosis; (5) new
      laboratory findings; and (6) new considerations in the differential diagnosis.
      The most important achievement in recent years, however, is the mapping of the
      FMF susceptibility gene to chromosome 16p, a finding that raises hopes for prompt
      cloning of the gene and elucidation of the mechanisms involved in FMF expression.

PMID- 8989807
TI  - Tuberculosis among Filipino patients with systemic lupus erythematosus.
AB  - A retrospective review of the clinical records of 54 patients with systemic lupus
      erythematosus (SLE) and documented tuberculosis (TB) infection seen at the
      University of Santo Tomas Hospital was accomplished. There were 53 women and one
      man, with a mean age of 32.2 +/- 10 years and a total of 57 TB occurrences.
      Pulmonary involvement was recorded in 42 (74%): upper lungfield in 25, mid to
      lower lungfield in 7, and miliary pattern or diffuse infiltrates in 10. TB
      arthritis was noted in 8, osteomyelitis in 4, and soft tissue abscesses in 4.
      Central nervous system involvement consisted of brain abscesses (tuberculomas) in
      two and meningitis in one. Two patients each had TB lymphadenitis, genitourinary
      TB, ileocecal TB, and TB peritonitis. Hepatobiliary and cutaneous TB occurred in
      one patient each. Eight of 10 patients with disseminated or miliary TB died
      primarily of respiratory failure; six of these eight patients also had some form
      of extrapulmonary involvement. Using the Wilcoxon rank-sum test, there were
      significant differences in the mean SLE Disease Activity Index (SLEDAI) and
      Severity of Disease Index (SDI) scores between those with limited TB (SLEDAI 24
      +/- 7 SD; SDI 19 +/- 18 SD) versus those with extensive TB (SLEDAI 41 +/- 16 SD;
      SDI 36 +/- 21 SD), P < .05. There was no significant difference in the average
      daily prednisone dose (mg) between those with limited TB (25 +/- 17 SD) versus
      those with extensive TB (31 +/- 16 SD). The contributory role of tuberculous
      infection in the morbidity and mortality of patients with SLE must be emphasized,
      especially in areas endemic for TB.

PMID- 8989808
TI  - Aspergillosis in systemic lupus erythematosus.
AB  - Infection is the major cause of morbidity and mortality in systemic lupus
      erythematosus (SLE). Although various fungi account for a substantial number of
      these lethal infections, aspergillosis, an important opportunistic infection in
      immunosuppressed patients, is described rarely. Only 23 cases have been reported
      in the English-language medical literature. Risk factors for acquiring
      aspergillosis in these patients were high grade disease activity,
      granulocytopenia, use of steroids and other immunosuppressive treatment and
      presence of bacterial infection. The diagnosis in most patients was delayed and
      they died. Here, we describe three SLE patients with invasive aspergillosis.
      Features of our patients' diseases were similar to those reported previously.
      Aspergillosis appeared while they had active SLE treated with high dose
      corticosteroids. In 2 patients the fungal infection was systemic and diagnosed
      post mortem. Both were leukopenic and had concurrent bacterial infection and one
      received amphotericin B prior to death. In the third, the infection was localized
      to a transplanted kidney and was cured by nephrectomy. Aspergillosis should be
      suspected in patients with active SLE, who are immunocompromised and sustain
      concomitant bacterial infections. The currently poor prognosis may be improved
      with more aggressive diagnostic investigation and treatment.

PMID- 8989809
TI  - The neurobiology of hepatic encephalopathy.

PMID- 8989810
TI  - Astrocytic-ammonia interactions in hepatic encephalopathy.

PMID- 8989811
TI  - Natural benzodiazepines and hepatic encephalopathy.

PMID- 8989812
TI  - Animal models of hepatic encephalopathy.

PMID- 8989814
TI  - Cerebral circulation in liver failure: Ohm's law in force.

PMID- 8989813
TI  - Brain edema and hepatic encephalopathy.

PMID- 8989815
TI  - Noninvasive neuroinvestigation in liver disease.
AB  - The advent of magnetic resonance imaging (MRI) and spectroscopy (MRS) and of
      single photon and positron emission tomography (SPET:PET) has allowed acquisition
      of data, not otherwise available, on cerebral metabolic function in patients with
      hepatic encephalopathy. Hyperintensity of the globus pallidus has been observed
      in cerebral T1-weighted MR images in patients with sub-clinical or overt hepatic
      encephalopathy, most likely due to the deposition of manganese; these trace metal
      deposits reflect either intoxication or the presence of an adaptive process
      leading to improved efficacy of ammonia detoxification by astrocytes. Cerebral
      31P MRS has shown that there is no primary deficit in energy metabolism in
      patients with hepatic encephalopathy, but rather an impairment of phospholipid
      membrane metabolism; cerebral 1H MRS shows a characteristic pattern of
      abnormalities in these patients, namely, a significant increase in
      glutamine/glutamate and significant reductions in choline-containing compounds
      associated with phospholipid membrane metabolism and of myo-inositol which
      functions, in part, as an organic osmolyte. SPET and PET technology have not been
      adequately exploited in the study of hepatic encephalopathy to date; the few
      studies available have produced conflicting results, most likely because little
      or no account was taken of the effects of chronic liver disease, portal-systemic
      shunting or enhanced blood-brain barrier permeability on tracer-ligand
      availability. All of these techniques need to be further exploited in well
      characterized populations with, wherever possible, standardization of techniques
      between centers; the factors likely to affect tracer-ligand availability must be
      adequately controlled to allow correct interpretation of the data obtained.

PMID- 8989816
TI  - TIPS and hepatic encephalopathy.
AB  - The increasing use of TIPS in the treatment of complications of portal
      hypertension has to be reassessed, taking into account the substantial collective
      experience gained in many centers around the world. Specific indications need to
      be demonstrated using well-designed clinical trials, as it is now known that
      (contrary to the initial expectations), the true rate of post-TIPS encephalopathy
      is significant and likely to be similar to that observed shortly after shunt
      surgery. In many patients, the decreased incidence of post-TIPS HE observed
      during follow-up is related to progressive stenosis of the shunt. This is
      associated with the recurrence of portal hypertension and, often, with the onset
      of clinical complications such as ascites or variceal bleeding. Prospective
      studies are required to define the ideal compromise between portal decompression
      and maintenance of a certain amount of portal perfusion to the liver and, thus,
      some portal hypertension, but at a threshold level below that associated with an
      increased risk of clinical complications. TIPS must be regarded as only one of
      several therapeutic modalities available to treat portal hypertension. When TIPS
      induces disabling encephalopathy or accelerated liver failure, closure of the
      shunt should be performed early, and alternative treatments can be used,
      including endoscopic sclerotherapy, variceal ligation, large volume paracentesis,
      and, most importantly, liver transplantation. Hopefully, lessons from the past
      gleaned from the evaluation of surgical portacaval shunts in the treatment of
      portal hypertension will help to better define the appropriate use of TIPS in
      cirrhotic patients to maximize the beneficial effects of reducing the portal
      pressure while minimizing the deleterious effects of this procedure.

PMID- 8989817
TI  - Subclinical hepatic encephalopathy.

PMID- 8989818
TI  - Newer approaches to therapy of hepatic encephalopathy.

PMID- 8989819
TI  - Determinants of substrate specificity for factor XIII.
AB  - Plasma factor XIIIa (A*2) is a regulator in balancing the opposing coagulation
      and fibrinolytic processes. Its enzymatic activity is to catalyze epsilon-(gamma
      glutamyl)lysyl bonds between certain substrate molecules to link them by strong
      bonds. The primary physiological substrates are crosslinks between the gamma and
      alpha chains of fibrin that produce gamma-gamma-dimer and alpha-polymer, between
      alpha 2-plasmin inhibitor (alpha 2-PI) and alpha chains of fibrin, and between
      fibronectin and fibrin. We have characterized a unique factor XIII antibody that
      is specific for the middle 54-kDa section of A*2. It does not react with the
      zymogen (A2) or the inactive intermediate (A'2), and it does not inhibit the
      active center, as do most patient antibodies to factor XIII. This antibody
      inhibits the formation of A*2-fibrin complexes. Because of this specificity, the
      antibody was used to study other substrate interactions. It inhibited formation
      of fibronectin-factor XIIIa complexes, similarly to fibrin, and there was very
      little crosslinking of fibronectin to a fibrin clot. However, the amount of alpha
      2-PI crosslinked to a fibrin clot was normal. It was concluded that this antibody
      interferes with exosite binding of fibrin and fibronectin interferes with exosite
      binding of fibrin and fibronectin in a similar way, while at least one critical
      exosite binding domain for alpha 2-PI is different from those of the other two
      substrates. Furthermore, with this antibody, it was shown that both alpha 2-PI
      alpha chain crosslinking and alpha-polymer formation are necessary to normalize
      the rate of fibrinolysis.

PMID- 8989820
TI  - Structure and function studies of factor XIIIa by x-ray crystallography.
AB  - The three-dimensional structures of several forms of the factor XIII A subunit
      have been determined using single crystal x-ray diffraction methods. Our
      crystallographic studies have provided the first detailed structural view of the
      factor XIII A subunit and information that is useful for understanding
      transglutaminase function. We have identified a conserved Cys314-His373-Asp396
      catalytic triad of residues in the active site of the molecule and a number of
      other conserved residues that may play important roles as well. The calcium and
      strontium structures have revealed several conserved acidic residues (Asp438,
      Glu485, and Glu490) involved in ion binding. We have also been able to use our
      crystal structures as scaffolds to model the possible structural effects of
      missense mutations that have been identified in factor XIII-deficient patients.

PMID- 8989822
TI  - Gene defects in congenital factor XIII deficiency.
AB  - The knowledge of the molecular basis of factor XIII deficiency has improved
      significantly in recent years. Almost 20 different mutations have been described
      in the gene coding for the factor A-subunit and 3 mutations in the gene coding
      for the B-subunit. Half of the mutations in the factor XIIIa A-subunit gene are
      nonsense mutations that result in premature termination of translation. Three of
      them are frameshift mutations that are caused by minor deletions. Two of them are
      splicing mutations and 3 are stop mutations that are caused by single nucleotide
      substitutions. Ten of the mutations are missense mutations caused by nucleotide
      transitions leading to amino acid substitutions. In the factor XIII B-subunit
      gene, the 3 mutations are an amino acid substitution, a splicing mutation, and a
      trinucleotide insertion. These mutations explain the disease in the two families
      reported to have XIII B-subunit deficiency. In factor XIII A-subunit deficiency,
      the genetic defects have been characterized so far only in a minority of cases.
      In most of the reports of factor XIII A-subunit mutations, each family carries
      its own mutation/mutations. However, in some populations such as Finns and Arabs
      some enrichment of specific mutations has occurred. Some international migration
      of a few mutations has also been noted. The structural and functional effects of
      the mutations have been analyzed by studying the expression of the factor XIII
      subunits on mRNA and protein levels in vivo or in vitro, and by utilizing the
      three-dimensional model of crystallized factor XIII A-subunit in modeling of the
      missense mutations.

PMID- 8989821
TI  - The normal and abnormal genes of the a and b subunits in coagulation factor XIII.
AB  - Factor XIII consists of two catalytic a and two noncatalytic b subunits. The gene
      for the a subunit is located on chromosome 6, the gene for the b subunit on
      chromosome 1. Both genes have been characterized. There are several different
      allelic forms of the a subunit in the normal population and some
      microheterogeneity for the b subunit. Most patients with congenital factor XIII
      deficiency lack the a subunit in plasma; few patients appear to have a complete
      lack of the b subunit. The genes from patients with factor XIII deficiencies were
      obtained and examined. Based on these analyses a new genetic classification for
      factor XIII deficiency is proposed: a deficiency of the a subunit (formerly
      termed type II), a deficiency of the b subunit (formerly known as type I), and a
      possible combined deficiency of both a and b subunits.

PMID- 8989823
TI  - Intracellular factor XIII: cellular distribution of factor XIII subunit a in
      humans.
AB  - In addition to the plasma where factor XIII subunit A is present as part of the
      heterodimers of the tetrameric fibrin-stabilizing factor, homodimers of factor
      XIII A can also be detected in cellular localization in different human tissues.
      Experimental findings verified that these cells belong to the megakaryocyte/
      platelet and the monocyte/macrophage cell lines. Additionally, factor XIII A is
      present in hepatocytes localized mainly around central veins in the liver and
      occasionally expressed in certain malignantly transformed cells. It is reasonable
      to suppose that factor XIII A acts not only as a member of the clotting cascade,
      but also as a cellular enzyme that can catalyze molecular interactions
      intracellularly (during the assembly/reassembly of the cytoskeleton) or
      extracellularly (in the connective tissue matrix around the cells containing it).

PMID- 8989824
TI  - Platelet-associated factor XIII in platelet activation, adhesion, and clot
      stabilization.
AB  - Platelet-associated factor XIII provides a means by which to promote clot
      stabilization and platelet interaction with proteins of the coagulation and
      fibrinolytic pathways. In addition to its intracellular role within the platelet
      cytoplasm, activated factor XIII will bind to the surface of activated platelets.
      These platelets then participate in cell-cell or cell-clot interactions, thereby
      increasing the local concentration of factor XIIIa. The platelet-associated
      factor XIIIa may increase the amount of crosslinking in a fibrin clot, thereby
      contributing to the aging of the clot and the reduction in the degree of platelet
      binding. Clot resistance to fibrinolysis is enhanced by platelet factor XIIIa
      mediated crosslinking of alpha 2-antiplasmin to fibrin. The binding of factor
      XIIIa to the platelet surface requires the activation of the platelet fibrinogen
      receptor, glycoprotein IIb-IIIa. Thus, platelet-associated factor XIIIa may be
      used as a marker of in vivo platelet activation. Since half of the factor XIII
      present in blood is provided by the platelets, it is not surprising that this
      form of factor XIII plays an important role in hemostasis.

PMID- 8989825
TI  - ETRO Working Party on Factor XIII questionnaire on congenital factor XIII
      deficiency in Europe: status and perspectives. Study Group.
AB  - A questionnaire was sent out in 1993 to more than 350 European institutions
      caring for patients with hemorrhagic disorders with the request to provide data
      of patients with congenital factor XIII deficiency, to pursue the following aims:
      (1) establish a registry of congenital factor XIII deficiency patients, (2)
      promote exchange between clinicians and basic researchers, (3) improve diagnostic
      and therapeutic approaches, and (4) stimulate research on gene defects and their
      impact on factor XIII function. So far, 72 patient questionnaires from 60
      families have been collected. Their bleeding pattern is typical, with frequent
      involvement of the umbilical cord and the central nervous system. Forty-nine
      patients receive regular factor XIII replacement, but obviously some patients
      with mild symptoms do not require prophylactic substitution, despite low factor
      XIII levels. On the other hand, 18 patients had factor XIII activities of > or =
      5% of normal, but only 3 of those patients were reported to have no bleeding
      symptoms. Furthermore, 17 symptomatic, apparently heterozygous relatives in eight
      families were observed. Seven out of 30 females aged over 18 years had
      experienced spontaneous abortions; wound healing problems were seen in 26
      patients. Currently, a second questionnaire is being distributed to obtain more
      detailed information on bleeding and other symptoms, diagnostic approaches, and
      exclusion of concurrent other bleeding diatheses. Future activities will be
      validation and standardization of assays, and study of gene defects and their
      impact on the structure of factor XIII and symptoms of patients. We intend to
      expand the survey to countries outside Europe.

PMID- 8989826
TI  - Factor XIII deficiency: pathogenic mechanisms and clinical significance.
AB  - Congenital factor XIII deficiency is a rare disease, but has provided valuable
      information on the physiological role of factor XIII and the benefit of factor
      XIII replacement therapy. It could be shown that not only homozygous patients but
      also heterozygotes are at risk for bleeding complications. Acquired factor XIII
      deficiency, however, is much more common, and preliminary studies suggest a lack
      of factor XIII to be an important feature of various diseases. In acute states
      and severe hemorrhages, replacement therapy with factor XIII concentrates is
      recommended. Recent progress in assay methods and future clinical studies should
      help to evaluate the therapeutic potential of factor XIII.

PMID- 8989827
TI  - Therapeutic factor XIII preparations and perspectives for recombinant factor
      XIII.
AB  - With the increasing availability of human plasma this source was used to
      substitute for the production of factor XIII concentrate from placenta. Prior to
      changing the source material, the virus safety in accordance with the Committee
      for Proprietary Medicinal Products (CPMP) guidelines and the half-life were
      investigated. Concerning the virus safety, the following cumulative log 10
      clearance factors were obtained: human immunodeficiency virus (HIV) > or = 18.9,
      herpes simplex virus (HSV-1) > or = 21.5, polio > or = 19.1, bovine viral
      diarrhea virus (BVDV) > or = 13.3. Half-life studies of factor XIII from plasma
      in comparison with factor XIII from placenta were done in rabbits by
      determination of the antigen and in patients with congenital factor XIII
      deficiency by determination of the activity and antigen. In rabbits, the terminal
      half-life of the antigen was 78.2 hours for factor XIII from placenta and 87.0
      hours for factor XIII from plasma. In patients the half-lives were similar: 9.2
      days for activity and antigen of factor XIII from plasma and 8.5 days (activity)
      versus 9.4 days (antigen) for the placenta-derived factor XIII. Some further
      clinical studies with factor XIII concentrates are also reviewed. Newer
      developments concerning recombinant factor XIII, its expression,
      characterization, and properties are summarized. Concerning the physicochemical
      data, the behavior in plasma was characterized by the formation of high-molecular
      weight complexes, and first in vivo results, the recombinant factor XIII product
      was comparable to the naturally occurring material.

PMID- 8989828
TI  - Tissue transglutaminase and factor XIII in cartilage and bone remodeling.
AB  - While it is well established that factor XIII functions in crosslinking of the
      fibrin clot during blood coagulation and in wound healing, the physiological role
      of tissue transglutaminase is still unclear. Recent studies suggest that the
      expression of tissue transglutaminase correlates with (terminal) differentiation
      of cells and that the enzyme may play a role in extracellular matrix remodeling.
      In cartilage, tissue transglutaminase expression is restricted to hypertrophic
      chondrocytes and the enzyme is externalized at a distinct step in the chondrocyte
      maturation program. Upon activation by Ca2+, the transglutaminase modifies matrix
      constituents in a way that might predispose the matrix for the subsequent
      mineralization. Crosslinks of the structure gamma-glutamyl-epsilon-lysine are
      also abundant in bone matrix, but the transglutaminase expressed by osteoblasts
      and presumably involved in crosslinking of newly formed osteoid is likely to be
      distinct from both tissue transglutaminase and factor XIII. Matrix proteins
      thought to be crosslinked by transglutaminases in cartilage and bone matrix
      include glycoproteins such as osteonectin, osteopontin, fibronectin, fibrillin,
      and collagens II, III, V, and XI. Expression of the A subunit of factor XIII is
      restricted to megakaryocytes in the bone marrow cavity, and factor XIIIa is
      abundant in platelets that probably provide the major source for factor XIII in
      plasma.

PMID- 8989829
TI  - Factor XIII in ulcerative leg disease: background and preliminary clinical
      results.
AB  - The therapy concept of topical factor XIII application was developed on the basis
      of clinical and experimental investigations on improvement of wound healing, as
      well as on the morphological and pathophysiological topical site of venous
      ulcers. Topical treatment with factor XIII is special with regard to mode of
      application as well as efficacy, since a lot of other medications used for local
      wound treatment contain a fibrinolytic component. In the last 32 months, 23
      inpatients (17 female, 6 male) averaging 62.9 +/- 14.1 years and suffering
      ulcerative leg disease were treated with topically applied factor XIII. The
      average period of distal venous ulcer in these patients was 3.3 +/- 2.04 years.
      The extent of the ulcer surface ranged between 2.5 x 3.0 cm (minimum) and 18.5 x
      8.0 cm (maximum). All patients had been in medical consultation for several
      years. The venous ulcers were based upon a "postthrombotic syndrome" in 15
      patients. Six patients were suffering from ulcerations due to arterial and venous
      mixed disease, and there were 2 patients with ulcerations of unknown etiology. In
      5 patients, 2 with unknown etiology and 3 with arterial and venous mixed disease,
      local treatment with factor XIII was discontinued after 4 weeks because there was
      definitely no improvement in wound healing. Additionally, 3 patients with
      ulcerations due to arterial and venous mixed disease were treated for a maximum
      of 6 weeks with only moderate improvement in healing. Twelve of the 15 patients
      (79.3%) with extended, chronic ulceration on the basis of a postthrombotic
      syndrome showed such a distinct improvement of topical site after an average of
      only 3.15 +/- 1.14 weeks that they were released for further ambulatory
      treatment. Three patients had to be treated for a maximum period of 6 weeks, also
      with distinct improvement in wound healing. Apart from a wound surface reduction
      and a clinically documentable improvement of granulation tendency, there was a
      marked reduction of secretion and bleeding tendency within the ulcer area
      observed in all patients. None of the patients showed any systemic or local
      allergic reactions.

PMID- 8989830
TI  - Factor XIII in chronic inflammatory bowel diseases.
AB  - Severe acute inflammation in chronic inflammatory bowel disease is associated
      with large wound areas and ulcerations that show spontaneous hemorrhage or marked
      friability. Therefore, an enormous potential of hemostasis and wound healing is
      required. Coagulation studies demonstrate a deficiency of factor XIII that is
      important for both clot formation and wound healing. Consequently, the
      substitution of factor XIII may be beneficial; the first case reports present
      favorable clinical results. In a prospective pilot study, we treated 12 patients
      with therapy-resistant ulcerative colitis. The colitis activity index (CAI) and
      the endoscopic score (ES) according to Rachmilewitz were elevated; all patients
      suffered from hematochezia. After substitution therapy with factor XIII
      concentrate (1,250 U/d) the stool frequency dropped and no further hematochezia
      was detected. The CAI and the ES declined highly significantly. Because of these
      encouraging results two placebo-controlled multicenter trials have been
      initiated. In the first study, patients with acute stage of ulcerative colitis
      associated with severe intestinal blood loss are treated with two different
      dosages of factor XIII concentrate (1,250 and 500 U/d, respectively) or placebo
      for 10 days. In the second trial, patients with therapy-resistant ulcerative
      colitis with a lack of remission in spite of a consequent therapy for 2 weeks are
      included; factor XIII concentrate or placebo is administered for 10 days. The aim
      of both trials is an end of intestinal bleeding and the fostering of a more
      effective wound-healing process.

PMID- 8989831
TI  - Regulation of skeletal muscle protein turnover during sepsis: mechanisms and
      mediators.
AB  - Skeletal muscle protein wasting is a prominent feature of the metabolic response
      to sepsis. Persistent protein wasting leads to muscle dysfunction and prolongs
      recovery from the septic insult. Unfortunately, conventional nutritional support
      alone does not prevent the sepsis-induced weight loss and catabolism of muscle.
      Hence, mechanisms other than substrate deficiency appear to be involved in the
      derangements in protein metabolism during sepsis. The catabolism of muscle during
      sepsis results from a stimulation of proteolysis and an inhibition of protein
      synthesis. This review summarizes the mechanisms responsible for alterations in
      protein synthesis and degradation in muscle during sepsis at the biochemical
      level. The ability of hormones (insulin, insulin-like growth factor I,
      glucocorticoids) or cytokines (tumor necrosis factor, interleukin-1) to act as
      mediators of protein catabolism is also examined. Finally, we discuss the
      potential role of anticytokine therapies in preventing derangements in protein
      metabolism during sepsis. A picture is emerging which suggests that cytokines may
      influence skeletal muscle protein metabolism during sepsis both indirectly
      through inhibition of the regulatory actions of anabolic hormones on protein
      turnover, and directly through modulation of the protein synthesis and
      degradation enzymatic machinery.

PMID- 8989832
TI  - Plasma nitric oxide in posttrauma critical illness: a function of "sepsis" and
      the physiologic state severity classification quantifying the probability of
      death.
AB  - The time course of nitric oxide (NO) production in posttrauma critical illness
      was monitored, and its relationship to posttrauma "sepsis/SIRS" and physiologic
      patterns was described. Eighty multiple trauma patients were studied (514
      samples) during their course in the intensive care unit (Injury Severity Score
      27.6; 36% deaths). Plasma NO was estimated from NO3 + NO2 by the Griess test and
      compared with that of 10 healthy controls (HC). At each sample period, the
      patient was categorized as having bacteremic sepsis (BAC), sepsis syndrome (SS),
      or systemic inflammatory response syndrome (SIRS), and classified by Physiologic
      State Severity Classification (PSSC) into normal stress response (A-State),
      metabolic insufficiency (B-State), or respiratory insufficiency (C2-State), each
      quantified by their physiologic "distance" from reference state of recovering
      trauma patients (R-State). A severity index (L2PDEATH), based on a logistic model
      of state distances from R-State, quantified probability of death. Deaths showed
      increased NO (p < .05) over survivors or HC by day 3 posttrauma. A fall in
      vascular tone in deaths was related to the increased NO (p < .0001). The level of
      NO was higher as sepsis worsened: BAC > SS > SIRS > HC (all simultaneous, p <
      .05). PSSC and L2PDEATH correlated with incidence > HC and level of NO. In
      conclusion, the severity of posttrauma critical illness was classified by PSSC
      and quantified by the L2PDEATH index. These reflect progressively increased NO
      levels and suggest worsening sepsis status. The reduced total peripheral
      resistance (TPR)-to-flow relationship (vascular tone) in deaths characteristic of
      the more severe septic PSSC states appeared related to the increased plasma NO.

PMID- 8989833
TI  - Nitric oxide regulation of interleukin-8 gene expression.
AB  - While the regulation of nitric oxide (NO) by inflammatory cytokines or
      lipopolysaccharide (LPS) has received considerable attention, NO modulation of
      cytokine expression has yet to be fully explored. The NO synthase inhibitor, NG
      nitro-L-arginine methyl ester (L-NAME), inhibited interleukin (IL)-8 and IL-6
      production in LPS-stimulated human whole blood in a dose-dependent manner. In the
      presence of 1 microgram/mL LPS, L-NAME blocked IL-8 release (72 +/- 4% inhibition
      at 20 mM (mean +/- SEM, p < .05)) 24 h post-LPS without affecting cellular
      viability. IL-6 production was significantly inhibited only with the highest dose
      of L-NAME used. L-NAME inhibition of IL-8 production was also observed at the
      mRNA level. Conversely, direct exposure of whole blood to NO with the spontaneous
      NO liberator DETA NONOate caused a dose-dependent stimulation of IL-8, but had no
      effect on IL-6 release. IL-8 concentrations rose from 8.3 +/- 1.9 ng/mL at 24 h
      to 31.7 +/- 7.6 ng/mL at 72 h with a single stimulation of 10 mM DETA NONOate.
      The hydroxyl radical scavenger dimethyl sulfoxide (DMSO) prevented the DETA
      NONOate induction of IL-8, suggesting the participation of the hydroxyl radical
      in the NO-induced IL-8 production. These results provide important evidence
      substantiating a role for NO as a regulator of cytokine expression.

PMID- 8989834
TI  - Selective inhibition of receptor-mediated pulmonary vasorelaxation in endotoxin
      induced acute lung injury.
AB  - We hypothesized that pulmonary vasorelaxation mediated by receptors that require
      generation of cyclic adenosine monophosphate (cAMP) is impaired in endotoxin
      induced acute lung injury. The purpose of this study was to determine the effect
      of endotoxin on the following pathways of pulmonary vasorelaxation that require
      the generation of cAMP: 1) beta-adrenoreceptor stimulation (response to
      isoproterenol, ISO), 2) P2 purinoreceptor stimulation (response to adenosine
      diphosphate, ADP), 3) H2-histamine receptor stimulation (response to dimaprit),
      4) adenosine A2 receptor stimulation (response to adenosine, ADO), 5) type 2 E
      prostaglandin (EP2) receptor stimulation (response to prostaglandin E1, PGE1),
      and 6) direct adenylate cyclase stimulation (response to forskolin, FSK). We used
      isolated pulmonary artery rings harvested from rats injected with endotoxin or
      saline. We found that endotoxin impaired the response to beta-adrenoreceptor
      stimulation (ISO) and P2 purinoreceptor stimulation (ADP). Endotoxin converted
      the vasorelaxant effect of H2-histamine receptor stimulation (dimaprit) to
      vasoconstriction. On the other hand, the response to A2 receptor stimulation
      (ADO) and EP2 receptor stimulation (PGE1), was normal. The dose response to
      direct adenylate cyclase stimulation (FSK) was the same as control except at a
      single concentration (10(-7) M). These data suggest that endotoxin causes
      selective impairment of pulmonary vasorelaxation through receptors coupled to
      cAMP generation. This impaired pulmonary vasorelaxation may contribute to the
      increased pulmonary vascular resistance seen in acute lung injury. These data may
      lead to therapy that will prevent or improve the pathophysiologic pulmonary
      circulation in acute lung injury.

PMID- 8989835
TI  - Impaired bacterial clearance after activation of the complement and coagulation
      systems.
AB  - The aim of this study was to investigate the influence of the activation of the
      complement and coagulation systems on bacterial clearance and killing capacity of
      the reticuloendothelial system in rabbits. To enable quantification of the
      clearance process, defined numbers of exogenous Escherichia coli (1.3 x 10(8)
      colony-forming units) were injected intravenously, after complement activation
      with inulin-activated rabbit serum (n = 6), after complete defibrination with the
      snake toxin ancrod (n = 6), and in sham-operated animals (controls, n = 6).
      During the following 180 min observation period, parameters monitored were
      arterial pressure, fibrinogen, blood gases, and bacterial counts in blood and
      tissue samples of liver, kidney, spleen, and lung. Defibrination produced a
      significant delay in blood clearance (p < .05) compared with controls, coupled
      with up to four times higher bacterial counts in organ homogenates. Complement
      activation did not affect bacterial elimination kinetics, but was associated with
      accumulation of E. coli in lung and kidney (up to 100-fold of control values, p <
      .001). The impaired bacterial clearance associated with increased organ
      colonization after activation of the complement and coagulation systems reflect
      reticuloendothelial system dysfunction, thus pointing toward a weaker resistance
      against bacterial infection.

PMID- 8989836
TI  - Endotoxin-induced microvascular leakage is prevented by a PAF antagonist and NO
      synthase inhibitor.
AB  - The hamster cheek pouch was used to determine the role of platelet activating
      factor (PAF) and nitric oxide (NO) in leukocyte adhesion and microvascular
      leakage of FITC-dextran following systemic administration of endotoxin. Endotoxin
      (5 mg/kg, i.v.) or vehicle was administered to the hamster 15 min after systemic
      pretreatment with either a PAF antagonist (Abbott-87648, .1 mg/kg, i.v.) or a
      nitric oxide synthase inhibitor (L-NAME, 30 mg/kg, i.v.), or 60 min after
      dexamethasone pretreatment (4 mg/kg, i.p.). Endotoxin alone caused rapid leakage
      of FITC-dextran from the vascular compartment into the tissue. This leakage was
      not preceded by either increased leukocyte rolling or adhesion in postcapillary
      venules. Pretreatment with the PAF antagonist, as well as with dexamethasone,
      completely blocked endotoxin-induced leakage. L-NAME also blocked endotoxin
      induced leakage; however, more than 50% of the hamsters treated with L-NAME died
      within 2 h after endotoxin administration. These results suggest that PAF and NO
      are important mediators of microvascular leakage during endotoxemia and that
      their actions are not dependent on leukocyte adhesion to postcapillary venular
      endothelium.

PMID- 8989837
TI  - Dehydroepiandrosterone, an endogenous immune modulator, after traumatic shock.
AB  - Dehydroepiandrosterone (DHEA), an endogenous immune modulator, reduces mortality
      after endotoxin (lipopolysaccharide (LPS)) administration in rodents. However,
      there have been no studies in clinically relevant large-animal models. A unique
      experimental model is used to study the effects of DHEA in resuscitated trauma
      and to evaluate the protective effect of DHEA on the systemic inflammatory
      response induced by a delayed LPS challenge. Anesthetized, ventilated pigs were
      instrumented and then subjected to local hind-limb trauma and 35% hemorrhage.
      After 1 h, animals were resuscitated with shed blood, supplemental Ringers
      solution, and in a randomized, blinded fashion, 4 mg/kg of DHEA or vehicle. Two
      additional groups received 10 mg/kg or 20 mg/kg of DHEA. Animals were dosed again
      at 24, 48, and 72 h. After 75 h, Escherichia coli LPS was administered. LPS
      caused a fall in DHEA levels (0.23 +/- .05 ng/mL (60 min post-LPS) versus .94 +/-
      35 ng/mL (72 h), p = .01). DHEA levels 60 min post-LPS were significantly higher
      in treated animals (p < .002). After LPS, all groups manifested progressive
      septic symptoms with a hyperdynamic state and pulmonary failure. These symptoms
      were not blunted by the administration of DHEA. DHEA levels are suppressed by LPS
      in this two-stage model of trauma and delayed sepsis; however, exogenous DHEA
      administration fails to blunt the associated systemic inflammatory response and
      pulmonary failure.

PMID- 8989839
TI  - Adrenocorticotropin correlates strongly with endotoxemia after intravenous but
      not after intraperitoneal inoculations of E. coli.
AB  - To determine the influence of the site of infection on circulating endotoxin and
      hormonal release, male rats were prepared with arterial catheters and with either
      intravenous (i.v.) or intraperitoneal (i.p.) catheters under pentobarbital. Four
      days later, they were injected either i.v. or i.p. with Escherichia coli
      suspended in saline. Plasma was assayed for adrenocorticotropin (ACTH),
      corticosterone, and endotoxin activity. After approximately 10(9) colony-forming
      units (CFU) of E. coli, plasma endotoxin in i.v. rats (496 +/- 96 EU/mL) differed
      from that in i.p. rats (12.6 +/- 3.6 EU/mL, p < .01). However, ACTH and
      corticosterone increased to the same extent in both groups. After approximately
      10(7) CFU, plasma endotoxin in i.v. rats (9.15 +/- 2.09 EU/mL) was greater than
      in i.p. rats (2.56 +/- .42 EU/mL, p < .05), and ACTH and corticosterone increased
      more at 1 h in i.v. rats than in i.p. rats (p < .01). Additional rats given
      approximately 0.3 x 10(9) CFU i.p. had plasma endotoxin that did not differ from
      values measured after either approximately 10(9) CFU i.p. or approximately 10(7)
      CFU i.v. However, the ACTH responses in these three groups differed from one
      another (p < .01). ACTH was more strongly correlated to plasma endotoxin in i.v.
      rats (r = .915) than in i.p. rats (r = .528, p < .01 for difference from i.v.
      group). The weak relationship between plasma endotoxin and ACTH after i.p.
      inoculations suggests that peritoneal infections activate important pathways that
      are independent of the circulation.

PMID- 8989838
TI  - The importance of delta and kappa opioid receptors in the property of thyrotropin
      releasing hormone against hemorrhagic shock.
AB  - Many studies have demonstrated that thyrotropin-releasing hormone (TRH) produces
      various beneficial effects in the treatment of shock. TRH has been proposed to
      reverse the cardiovascular depression of endogenous opioid peptides.
      Nevertheless, it remains unknown whether opioid receptors are truly involved in
      this process. We designed experiments to study the importance of delta and kappa
      opioid receptors in the beneficial effects of TRH in hemorrhagic shock in rabbits
      and on opiate receptors following hemorrhagic shock in rats. The results
      indicated that TRH (50 micrograms, i.c.v.) significantly improved the mean
      arterial pressure (MAP), left ventricular systolic pressure (LVSP), and the
      maximal rate of ventricular systolic pressure changes (+/- dp/dtmax) during
      hemorrhagic shock in rabbits. This TRH effect was abolished by pretreatment with
      ICI174,864 (50 micrograms, i.c.v.), a highly selective delta opioid receptor
      antagonist, but not by pretreatment with nor-binaltorphimine (Nor-BNI, 50
      micrograms, i.c.v.), a highly selective kappa opioid receptor antagonist. The
      maximal binding capacity (Bmax) of brain delta and kappa opioid receptors
      significantly increased following hemorrhagic shock, but the receptor affinity
      (Kd) did not change. TRH (5 mg/kg, i.v.) decreased the number (Bmax) of brain
      delta opioid receptors significantly, but it did not influence the receptor
      affinity. TRH did not influence the Bmax or affinity of brain kappa opioid
      receptors. These findings suggest that opioid receptors play an important role in
      mediating the antishock property of TRH. TRH-induced down-regulation of the
      number of brain opioid receptors may be one of the important mechanisms by which
      TRH exercises its protective effects in the treatment of shock.

PMID- 8989840
TI  - Circulatory failure induced by 35 GHz microwave heating: effects of chronic
      nitric oxide synthesis inhibition.
AB  - Sustained exposure to radiofrequency radiation of millimeter wave (MMW) length
      produces hyperthermia and subsequent circulatory failure. This study sought to
      determine whether this phenomenon is altered by chronic pretreatment with the
      nitric oxide (NO) synthesis inhibitor N omega-nitro-L-arginine methyl ester (L
      NAME). Rats drank either 1) water, 2) water + L-NAME, or 3) water + L-NAME + L
      arginine (at 20 and 50 times the dose of L-NAME) for 14 days. Ketamine
      anesthetized rats were exposed to MMW until mean arterial blood pressure (MAP)
      fell to 75 mmHg, at which point MMW exposure was discontinued. MAP initially
      increased during exposure in all groups; the pressor response in L-NAME-treated
      rats was greater than that in water-drinking rats. Subsequently, MAP fell in all
      groups. The MMW exposure time required to reach MAP = 75 mmHg was significantly
      reduced in L-NAME-treated rats, although survival times (post-MMW) of L-NAME
      treated and control rats were not statistically different. Coadministration of L
      arginine abolished the enhanced pressor response produced by L-NAME, but did not
      completely reverse the shortened MMW exposure time in L-NAME-treated rats. Thus,
      chronic NO synthesis inhibition with L-NAME reduces the ability of rats to
      withstand 35 GHz microwave heating, suggesting that NO does not mediate the
      hypotension produced by this form of hyperthermia.

PMID- 8989841
TI  - Breast-feeding exposure of infants to environmental contaminants--a public health
      risk assessment viewpoint: chlorinated dibenzodioxins and chlorinated
      dibenzofurans.
AB  - Exposure of children to chlorinated dibenzodioxins and chlorinated dibenzofurans
      via breast-feeding has been well-documented in industrialized countries. Recent
      studies indicate a possible link between development of subtle health effects in
      children and their exposure to dioxin-like chemicals from maternal milk. Some
      examples of the effects are lower vitamin K levels, increased thyroxine levels,
      and mild changes in liver enzymes. The projected daily intakes of chlorinated
      dibenzodioxins and chlorinated dibenzofurans are compared with minimal risk
      levels for intermediate duration oral exposure (15-365 days) derived for these
      chemicals. Public health recommendations for future actions related to infant
      intake of chlorinated dibenzodioxin- and chlorinated dibenzofuran-contaminated
      breast milk are also addressed.

PMID- 8989842
TI  - Dangerous and cancer-causing properties of products and chemicals in the oil
      refining and petrochemical industry--Part XXII: Health hazards from exposure to
      gasoline containing methyl tertiary butyl ether: study of New Jersey residents.
AB  - Methyl tertiary butyl ether has caused the following cancers in rats and mice:
      kidney, testicular, liver, lymphomas, and leukemias. Thus, in the absence of
      adequate data on humans, it is biologically plausible and prudent to regard
      methyl tertiary butyl ether-for which there is sufficient evidence of
      carcinogenicity in experimental animals-as a probable human carcinogen. This
      means that some humans are at extreme risk of contracting cancers resulting from
      their exposure to oxygenated gasoline containing methyl tertiary butyl ether.
      Immediately after the introduction of methyl tertiary butyl ether into gasoline,
      many consumers of this product in New Jersey, New York, Alaska, Maine,
      Pennsylvania, Colorado, Arizona, Montana, Massachusetts, California, and other
      areas, experienced a variety of neurotoxic, allergic, and respiratory illnesses.
      These illnesses were similar to those suffered by refinery workers from the Oil,
      Chemical, and Atomic Workers Union who mixed methyl tertiary butyl ether with
      gasoline. Additionally, these illnesses occurred following exposure to extremely
      low levels of methyl tertiary butyl ether in gasoline, particularly when compared
      to the adverse health effects that occurred only after exposure to very high
      levels of conventional gasoline. Thus, gasoline containing methyl tertiary butyl
      ether exhibited substantially more toxicity in humans than gasoline without this
      additive. A number of oil industry-sponsored or influenced reports alleged that
      these illnesses were either unrelated to exposure to reformulated gasoline or
      were characteristic of some yet-to-be-identified communicable disease. These
      studies further alleged that the widespread concern was not about illness, but
      was merely a reaction to the odor and the five cent increase in the price of
      gasoline. To clarify the significance of this issue, it is important to note that
      consumers have been using gasoline for many decades, with complaints only
      occurring following exposure to high levels at 100s ppm or higher. After the
      introduction of methyl tertiary butyl ether gasoline there were thousands of
      human health complaints. The sudden increase in widespread illnesses from which
      many thousands of individuals throughout the United States began to suffer
      immediately following the introduction of methyl tertiary butyl ether into
      gasoline provides strong and unquestionable evidence that gasoline containing
      methyl tertiary butyl ether is associated with human illnesses. When considering
      the severity of the illnesses in humans, it is prudent that this highly dangerous
      chemical be promptly removed from gasoline and comprehensive studies be conducted
      to assess the long-term effects that human may experience in the future from past
      and current exposure.

PMID- 8989843
TI  - Relationship of hemoglobin to occupational exposure to motor vehicle exhaust.
AB  - OBJECTIVE: To study the relationship of hemoglobin to exposure to motor vehicle
      exhaust. DESIGN: Survey. PARTICIPANTS: Traffic police, bus drivers, and auto-shop
      workers (all exposed to auto exhaust in Madras, India) and unexposed office
      workers. MAIN OUTCOME MEASURES: We measured levels of blood lead (by graphite
      furnace atomic absorption spectrophotometry), and hemoglobin. Information also
      was collected on age, employment duration, smoking status, alcohol ingestion, and
      diet type (vegetarian or nonvegetarian). RESULTS: Increasing exposure to motor
      vehicle exhaust, as reflected by job category, was significantly associated with
      lower levels of hemoglobin (p < 0.01). A final multivariate regression model was
      constructed that began with indicator variables for each job (with office workers
      as the reference category) and included age, duration of employment, blood lead
      level, alcohol ingestion, dietary type, and smoking status. After a backward
      elimination procedure, employment duration as an auto-shop worker or bus driver
      remained as significant correlates of lower hemoglobin level and current smoking
      and long employment duration as significant correlates of higher hemoglobin
      level. CONCLUSIONS: Occupational exposure to automobile exhaust may be a risk
      factor for decreased hemoglobin level in Madras. This effect appears to be
      independent of blood lead level and may represent hematopoietic suppression
      incurred by benzene or accumulated lead burden (which is not well reflected by
      blood lead levels). Smoking probably increased hemoglobin level through the
      chronic effects of exposure to carbon monoxide. In this study, a long employment
      duration may have served as a proxy for better socioeconomic, and therefore,
      better nutritional status.

PMID- 8989844
TI  - Toxicological and environmental health information from the National Library of
      Medicine.
AB  - The National Library of Medicine's Toxicology and Environmental Health
      Information Program is the outgrowth of a 1966 document on "Handling of
      Toxicological Information," prepared by the Presidents Science Advisory Committee
      (National Library of Medicine, 1995). The Toxicology and Environmental Health
      Program is responsible for the creation and deployment of both bibliographic and
      factual files concerned with toxicology, carcinogenesis, developmental and
      reproductive effects of chemical substances, toxic chemical releases, and the
      medical and environmental behavior of chemical substances. The two main computer
      systems that provide bibliographic and factual data banks are Toxicology Data
      Network (TOXNET) and ELHILL. A number of the files found in the TOXNET system are
      built and maintained by other federal agencies such as the National Cancer
      Institute, the U.S. Environmental Protection Agency, the National Institute for
      Occupational Safety and Health.

PMID- 8989845
TI  - Exposure measurement needs for hazardous waste sites: two case studies.
AB  - The science of exposure assessment has been expanding both its theoretical and
      experimental bases over the past two years. Recent theoretical work published by
      the authors in the Journal of Exposure Analysis and Environmental Epidemiology
      (Volume 4, Number 3, 1994) has defined a multistep process to couple measurement
      data with mathematical models of exposure and dose. The present manuscript
      discusses the need for improving the measurement of exposure in order to reduce
      uncertainties in the potential risk and, eventually, the occurrences of health
      outcomes in the community environment. The discussion focuses on hazardous waste
      sites and how improving or routinely introducing exposure measurements to the
      remedial investigation can lead to a better understanding of how the potential
      population can get exposed via single or multiple activities. This information
      can help to better understand the need for specific remediation actions and
      selection of the types of models that can be used to predict exposure for a large
      population and to estimate the reduction in postremediation exposure for a local
      population (National Research Council, 1991).

PMID- 8989846
TI  - Neurophysiological and neuropathological evaluation of primates exposed to
      ethylene oxide and propylene oxide.
AB  - Over 500,000 workers in the United States are exposed to ethylene oxide and
      propylene oxide. These two solvents are used as chemical intermediates, as well
      as components in the manufacture of fumigants and food preparation. The
      neurophysiologic and neuropathologic effects of these two organic oxides were
      investigated in five groups of 12 primates after exposure to 50 or 100 ppm
      ethylene oxide, 100 or 300 ppm propylene oxide, or no chemical (sham-exposed).
      Animals were exposed for 7 h/day, 5 days/wk for 24 months. Body weights,
      electroencephalograms, and motor nerve conduction velocities of the sciatic and
      ulnar nerves were assessed six times throughout the exposure period. Although the
      monkeys exposed to 100 ppm ethylene oxide had significantly lower mean weights,
      nerve conduction velocities did not differ significantly among the groups.
      Following termination of exposures, ten animals (two from each exposure group)
      were sacrificed for neuropathological examinations. Multiple axonal bodies were
      found in the nucleus gracilis in seven of eight oxide-exposed animals, and
      demyelination was found in two monkeys exposed to ethylene oxide. In contrast, a
      single axonal body was found in one of the two sham-control monkeys. However, the
      lack of a dose-response relationship suggests that this effect may not be related
      to oxide exposure. In a follow-up study, nerve conduction velocity and
      neuropathology were assessed in the remaining monkeys seven years after exposure
      terminated, but again, treatment-related effects could not be detected.

PMID- 8989847
TI  - An in vitro model for toxicological investigations of environmental neurotoxins
      in primary neuronal cell cultures.
AB  - Currently, most neurotoxicological investigations are still conducted using
      various animal models (e.g. chickens, rodents). In this report, alternative
      strategies of testing were examined to detect the neurotoxic potency of foreign
      compounds. Primary neuronal cell cultures from fetal rats are already an accepted
      model for mechanistic and pharmacological studies in drug research. Their
      suitability for neurotoxicological studies was examined by using industrial model
      compounds, which are well-known inductors of neuropathies: acrylamide,
      hexachlorophene, paraquat, n-hexane, and its neurotoxic metabolites acetylaceton
      and 2,5-hexandione. As a control compound, the nonneurotoxic solvent n-heptane
      was used. General cytotoxicity and the intracellular content of glial fibrillary
      acid protein, neuron-specific enolase, and neurofilaments were measured. n
      Heptane induced an acute cytotoxicity and acrylamide and 2,5-hexandione produced
      a delayed cytotoxicity in primary neuronal cells, whereas the others showed no
      cytotoxic potency in the tested concentration range. These results were in
      agreement with the quantification of neurons by neuron-specific enolase. In
      contrast, with the exception of acetylaceton, glia cells were significantly
      affected by all neurotoxins at the later time. Signs of axonopathies were
      demonstrated for acrylamide, n-hexane and its metabolites, as well as for
      hexachlorophene and paraquat in vitro, by determining the intracellular
      neurofilament level. Therefore, the determination of cell-specific end points is
      necessary to detect the neurotoxic potency and quality of a compound, whereas the
      cytotoxicity assay limited the tested concentration range.

PMID- 8989848
TI  - Treatment of organic water contaminants in oil refinery effluents investigated by
      using a simulation model.
AB  - In this paper the wastewater treatment of organic compounds, particularly the
      water soluble (polar) compounds in refinery effluents, is simulated by addressing
      biodegradation, adsorption, and stripping/volatilization. The study examines
      pollutant data from two refineries in Norway and one in the United States.
      Previously, little attention has been paid to polar compounds. However, they are
      present in effluents, sometimes in large amounts, and are difficult to
      characterize and quantify. The study shows that many polar compounds, including
      the recently introduced methyl-tertiary-butyl-ether, are biodegraded by < 10% in
      simulated wastewater treatment. The concentrations of some polymers are barely
      reduced at all, and some metabolites of nonionic surfactants increase in toxicity
      along the route of degradation, resulting in an end product of the highest
      toxicity. The study demonstrates that of the substances entering the treatment
      systems, the residual of selected polar compounds is 38% of the incoming amount,
      while oil is reduced to 8%. It can be inferred from the study that polar
      compounds are contaminants, many of which may pose a pollution problem, and that
      reduction of polar compounds in effluents should be carried out upstream at the
      source of pollution, rather than downstream by end-of-pipe treatment.

PMID- 8989849
TI  - Sperm chromatin structure is altered in cynomolgus monkeys with environmentally
      relevant blood lead levels.
AB  - Exposure to lead has been associated with a variety of adverse reproductive
      outcomes such as spontaneous abortion, impaired fecundity, and sterility.
      Although decreased sperm counts and serum testosterone levels have been found in
      men with occupational lead exposure, animal experiments suggest that fertility
      may be impaired at blood lead levels that have no apparent effect on reproductive
      hormone levels or sperm concentration. Consequently, this study investigated the
      effect of chronic lead treatment on semen quality in healthy cynomolgus monkeys
      aged 15-20 years with mean (+/-SD) blood lead levels of 10 +/- 3 micrograms/dL
      (range 6-20 micrograms/dL, n = 4) and 56 +/- 49 micrograms/dL (range 22-148
      micrograms/dL, n = 7) compared to a reference group with blood lead levels < 1.0
      microgram/dL (n = 8). Blood and semen samples were collected once from each
      monkey in five different months. Serum testosterone levels were determined by
      radioimmunoassay, and lead effects on chromatin structure were analyzed by flow
      cytometry. There were no effects of treatment on circulating levels of
      testosterone or parameters of semen quality such as sperm count, viability,
      motility, and morphology. However, significant (p < 0.03) treatment-related
      effects were seen on SD alpha t values in the treated vs control animals. Group
      comparisons also revealed that the effects of chronic lead exposure were
      significant (p < 0.05) for both lead-exposed groups compared to the reference
      group. We conclude that chronic lead exposure alters sperm chromatin structure at
      blood lead levels relevant to the human population and in the absence of effects
      on endocrine function and traditional measures of semen quality.

PMID- 8989851
TI  - Central nervous system oxygen toxicity during hyperbaric treatment of patients
      with carbon monoxide poisoning.
AB  - Hyperbaric oxygen (HBO2) is associated with a recognized risk for clinical
      central nervous system (CNS) toxicity. The risk for oxygen convulsions during
      routine hyperbaric treatment of most routine conditions is extremely low.
      Previous observations have suggested that the incidence of CNS toxicity during
      HBO2 treatment for carbon monoxide (CO) poisoning may be increased, both because
      of CNS injury caused by the poisoning and because higher treatment pressures are
      often utilized for this condition. This study reviews data from 900 CO-poisoned
      patients treated with HBO2 at Virginia Mason and Duke University Medical Centers
      from 1987 to 1996. One-third of the patient population was treated at each of the
      three HBO2 treatment pressures most commonly utilized for CO intoxication in
      North American multiplace chambers. Patient characteristics were similar in all
      groups. Among the 300 consecutive patients treated at each pressure, there was
      one seizure at 2.45 atm abs (0.3%), nine seizures at 2.80 atm abs (2.0%), and six
      seizures at 3.00 atm abs. This difference is statistically significant (P =
      0.032; Fisher's Exact Test). The potential difference in seizure risk should be
      considered when selecting the HBO2 treatment pressure for CO poisoning.

PMID- 8989850
TI  - Hyperbaric oxygen an adjunctive treatment for delayed radiation injuries of the
      abdomen and pelvis.
AB  - Radiation therapy is often utilized as adjunctive or primary treatment for
      malignancies of the abdomen and pelvis. Radiation complications are infrequent,
      but can be life threatening or significantly diminish the quality of life.
      Radiation necrosis is an approved indication for hyperbaric oxygen (HBO2).
      Previous publications have reported results in treating delayed radiation
      injuries involving many sites. This paper reports the experience of a single
      physician group in treating delayed injuries of the abdomen and/or pelvis. Forty
      four such patients have been treated since 1979. Of the 41 patients available for
      follow up, 26 have healed; 6 failed to heal; and 9 patients had an inadequate
      course of therapy (fewer than 20 treatments). Especially encouraging was the
      resolution of fistulae in six of eight patients with only three requiring surgery
      for closure. Overall, the success rate in patients receiving at least 20 HBO2
      treatments was 81%. Hyperbaric oxygen is a useful adjunct in treatment of delayed
      radiation injuries of the pelvis and abdomen.

PMID- 8989853
TI  - Testing of hypotheses about altitude decompression sickness by statistical
      analyses.
AB  - This communication extends a statistical analysis of forced-descent decompression
      sickness at altitude in exercising subjects (J Appl Physiol 1994; 76:2726-2734)
      with a data subset having an additional explanatory variable, rate of ascent. The
      original explanatory variables for risk-function analysis were environmental
      pressure of the altitude, duration of exposure, and duration of pure-O2 breathing
      before exposure; the best fit was consistent with the idea that instantaneous
      risk increases linearly as altitude exposure continues. Use of the new
      explanatory variable improved the fit of the smaller data subset, as indicated by
      log likelihood. Also, with ascent rate accounted for, replacement of the term for
      linear accrual of instantaneous risk by a term for rise and then decay made a
      highly significant improvement upon the original model (log likelihood increased
      by 37 log units). The authors conclude that a more representative data set and
      removal of the variability attributable to ascent rate allowed the rise-and-decay
      mechanism, which is expected from theory and observations, to become manifest.

PMID- 8989852
TI  - Effects of pressure on whole blood glucose measurements using the Bayer
      Glucometer 4 blood glucose meter.
AB  - The effect of pressure was investigated on the readings of whole blood glucose
      obtained from the Bayer Glucometer 4 blood glucose meter which uses the
      hexokinase enzymatic reaction. Sixteen subjects (eight normal and eight insulin
      dependent diabetics) were exercised in a hyperbaric chamber at a depth of 3.7 atm
      abs. Venous blood samples were monitored at regular intervals for whole blood
      glucose concentration as measured by a Glucometer 4 inside the chamber. The blood
      samples were immediately placed in an airlock and taken to 1 atm abs, where whole
      blood glucose concentrations were measured using an identical instrument. The
      remaining blood was then analyzed in duplicate for serum glucose concentration
      using standard laboratory methods. The results show a significant difference
      between whole blood glucose concentrations measured at pressure and those
      measured at atmospheric pressure. Significant differences are also observed
      between whole blood glucose concentrations measured under pressure and serum
      blood glucose concentrations measured at atmospheric pressure.

PMID- 8989854
TI  - A new method for measuring nitrogen and gases in blood.
AB  - The authors developed a new apparatus for extracting nitrogen or other inert
      gases from blood by flushing (sparging) the specimen with another gas. To
      investigate the utility of the new methodology, the apparatus was used in
      conjunction with a mass spectrometer to measure the blood N2 content of healthy
      normobaric, non-smoking, adult volunteers; the mean was found to be 11.7
      microliters/ml +/- 0.9 microliter. This compares closely with values cited in the
      literature. The within-subject variation for repeat samples taken several weeks
      apart was significantly (P < 0.003) less than the variation between different
      subjects, suggesting that there may be true differences in N2 content between
      different individuals. These data must be considered preliminary, a larger study
      is needed to investigate population differences in detail. The advantages of the
      new method are discussed.

PMID- 8989855
TI  - Case report on a diver with type II decompression sickness and viral meningitis.
AB  - A 33-yr-old man came to the emergency department with the chief complaint of a
      severe headache and decreased sensation in his right hand following a deep dive
      on scuba. Physical examination before recompression treatment was remarkable only
      for hypesthesia on the right hand. We diagnosed type II decompression sickness
      and the patient underwent standard recompression therapy. The patient experienced
      near-complete resolution of his symptoms, his only residual complaint being that
      of neck pain with head movement. To investigate other causes of headache, a
      computed tomography of the head was performed which was normal, and a lumbar
      puncture was performed which was consistent with viral meningitis. This is the
      first reported case of recompression treatment on a patient with viral meningitis
      and decompression sickness.

PMID- 8989856
TI  - Diffusion coefficients and solubility coefficients for gases in biological fluids
      and tissues: a review.
AB  - Based on a review of 166 references for diffusion and solubility coefficients in
      biological fluids and tissues, we have tabulated experimental values for the
      gases Ar, CO2, H2, He, N2, Ne, N2O, O2, and SF6. Two major conclusions can be
      drawn: a) for tissues, there is a scarcity of available data; and b) in general,
      there are significant differences between values determined by different
      investigators, the discrepancies being most prominent for diffusion coefficients.
      For water, we give numeric values of the temperature coefficients and preferred
      diffusion and solubility coefficients at 25 degrees and 37 degrees C. Further, we
      describe several methods for estimation of coefficients where experimental data
      are lacking. For tissues, none of the formulas described give precise predictions
      for all gases, but rough estimates sufficient for most qualitative work can
      almost always be found. In particular, the data material indicates that for all
      tissues other than fatty tissues consisting of mainly triacylglycerols, the
      solubility coefficients for water may be used as a good approximation. Except for
      SF6, the error in this approximation probably does not exceed 20%. In contrast,
      diffusion coefficients for most tissues are from 25 to 50% lower than the
      respective coefficients in water, generally increasing with the water content of
      the tissue.

PMID- 8989857
TI  - Improving text memory by organizing interfering text at retrieval.
AB  - We provide evidence that information that organizes interfering text after
      learning improves recall of original text to which the organizing information
      does not pertain. Subjects learned two text passages. The second passage was
      difficult to understand without the aid of a picture that provided the necessary
      clarifying context. Using the picture as an organizing cue for the second passage
      (just before retrieval of the first passage) improved recall of the first
      passage. We address and rule out an alternate explanation that is based on the
      difficulty of the task immediately preceding recall. These results contradict
      several traditional hypotheses about interference, and they are difficult to
      explain with several current models of memory. Implications for learning are
      discussed.

PMID- 8989858
TI  - The item-order distinction and the generation effect: the importance of order
      information in long-term memory.
AB  - The item-order distinction has been useful in explaining memory dissociations in
      short-term retention tasks. It generally has been assumed that serial order
      information is beneficial to long-term retention as well, although the
      distinction has received little empirical attention. Recently, it was shown that
      generating items at input, rather than simply reading them, hinders processing of
      serial order information. This reduction in order processing has been implicated
      in the lack of generation effects in between-list designs. Experiment 1, using
      typical generation effect procedures, showed that generation inhibited order
      reconstruction performance. Experiment 2 showed that order reconstruction was
      hindered even when categorically related lists were used. Experiment 3
      demonstrated that generation inhibited order reconstruction in an incidental
      learning procedure. The results suggest that order processing is relatively
      automatic and that generation constantly inhibits it. The results support the
      view that the item-order distinction may be a powerful explanatory tool in long
      term memory research.

PMID- 8989859
TI  - Segregation of yeast polymorphic STA genes in meiotic recombinants and analysis
      of glucoamylase production.
AB  - Hybrid yeast strains were constructed using haploid Saccharomyces cerevisiae and
      Saccharomyces cerevisiae var. diastaticus strains to get haploid meiotic
      recombinants having more than one copy of STA1, STA2, and STA3 genes. STA genes
      were localized on the chromosomes by pulsed field gel electrophoresis. Working
      gene dosage effects were found among STA genes in liquid starch medium,
      indicating low levels of glucose repression. Growth of strains, however, was not
      influenced by their STA copy number.

PMID- 8989860
TI  - Characterization of partial anaerobic metabolic pathway for 2,4,6-trinitrotoluene
      degradation by a sulfate-reducing bacterial consortium.
AB  - The anaerobic degradative pathway for metabolism of 2,4,6-trinitrotoluene (TNT)
      by a consortium of Desulfovibrio spp. isolated from a creek sediment was studied.
      This consortium has the metabolic capability to degrade TNT to fatty acids. The
      growth of the consortium and the metabolism of TNT were greatly enhanced in the
      presence of an additional carbon source like pyruvate. The optimal concentration
      of pyruvate for the maximum rate of TNT degradation was 15-20 mM. Various
      intermediates of TNT metabolism were identified. The first step in the pathway
      was reduction of TNT to 4-amino-2,6-dinitrotoluene and 2-amino-4,6
      dinitrotoluene, which were further reduced to 2,4-diamino,6-nitrotoluene. The
      next intermediate to appear in the culture medium was nitrobenzoic acid, followed
      by cyclohexanone, 2-methyl pentanoic acid, butyric acid, and acetic acid. A study
      using radiolabeled TNT showed that no CO2 was produced from TNT during
      metabolism. The mass balance of the radiolabeled study showed that 49.6% of the
      TNT was converted to acetic acid, 28% was assimilated into biomass as
      trichloroacetic acid precipitable materials, and the rest was distributed as
      various TNT intermediates. Most Desulfovibrio spp. are incomplete oxidizers that
      are unable to carry out the terminal oxidation of organic substrates. The major
      end product of TNT metabolism was acetic acid. The bacteria grew on all the TNT
      intermediates tested as sole source of carbon, except on acetic acid, confirming
      that the Desulfovibrio spp. have the enzymes necessary for complete degradation
      of TNT to acetate.

PMID- 8989861
TI  - Genetic variability of the common nod gene in soybean bradyrhizobia isolated in
      Thailand and Japan.
AB  - To determine the taxonomic relationship between Thai soybean bradyrhizobia and
      soybean bradyrhizobia from other regions, a total of 62 Bradyrhizobium strains
      were isolated in Thailand. The genetic diversity of the strains was examined with
      reference to 46 Japanese and 15 USDA strains. The degree of sequence divergence
      in and around common nod gene regions of the 123 strains was estimated by
      restriction fragment length polymorphism analysis using the Bradyrhizobium
      japonicum USDA 110 common nodDYABC gene probe. The phylogenetic grouping of the
      strains resulted in four major clusters. Cluster 1 comprised the Japanese and
      USDA strains, which originated in temperate regions, whereas clusters 3 and 4
      comprised the tropical Thai strains. Cluster 1 strains comprised the DNA homology
      groups I and Ia, and hence, were classified as B. japonicum. Cluster 2 strains
      were in the DNA homology group II, and hence, were classified as Bradyrhizobium
      elkanii. Clusters 3 and 4 strains, however, did not correspond to any known DNA
      homology groups. These results indicate that Thai soybean bradyrhizobia are
      distantly related to B. japonicum and B. elkanii.

PMID- 8989862
TI  - A dual cofactor-specific isocitrate dehydrogenase from Pythium ultimum.
AB  - Isocitrate dehydrogenase is considered to be one of the key regulatory enzymes in
      the conversion of glucose into fatty acids by oleaginous microorganisms. A dual
      coenzyme-specific isocitrate dehydrogenase (EC 1.1.1.41) (IDH) was isolated from
      the primitive fungus Pythium ultimum and purified by 211-fold by sequential ion
      exchange, affinity, and gel filtration chromatographies. Specific activity of the
      partially purified enzyme was 76.2 mumol/(min.mg protein) with NAD+ and 40% less
      active with NADP+. Optimum pH for activity was 8.5-9.5. K(m) values for threo-D
      isocitrate and NAD+ were 0.031 and 0.55 mM, respectively. The estimated molecular
      mass of the IDH was 96 kDa under nondenaturing conditions and 48 kDa under
      denaturing conditions, suggesting that the enzyme is composed of two subunits of
      the same size. The enzyme was relatively stable up to 55 degrees C, but no
      activity was detected after exposure to 65 degrees C for 15 min. Mg2+ or Mn2+
      were required for activity.

PMID- 8989863
TI  - Detection and identification of Entamoeba gingivalis by specific amplification of
      rRNA gene.
AB  - A pair of oligonucleotide primers were designed from the nucleotide sequence of
      the gene encoding the small subunit ribosomal RNA (SrRNA) of the oral protozoan
      parasite Entamoeba gingivalis. The primers amplified a 1.4-kb DNA fragment by
      polymerase chain reaction and were specific for Entamoeba gingivalis but not for
      other protozoa, oral protists and bacteria, or human leukocytes. With this
      method, the DNA from as few as 30 cells of Entamoeba gingivalis could be
      detected. These results suggest that this approach is applicable to the detection
      and identification of Entamoeba gingivalis in the human oral cavity.

PMID- 8989864
TI  - A Saccharomyces cerevisiae phleomycin-sensitive mutant, ph140, is defective in
      the RAD6 DNA repair gene.
AB  - The antibiotic bleomycin is used as an anticancer agent for treating a variety of
      tumours. The antitumour effect of bleomycin is related to its ability to produce
      lesions such as apurinic/apyrimidinic sites and single- and double-strand breaks
      in the cellular DNA. Phleomycin is a structurally related form of bleomycin, but
      it is not used as an anticancer agent. While phleomycin can also damage DNA,
      neither the exact nature of these DNA lesions nor the cellular process that
      repairs phleomycin-induced DNA lesions is known. As a first step to understand
      how eukaryotic cells provide resistance to phleomycin, we used the yeast
      Saccharomyces cerevisiae as a model system. Several phleomycin-sensitive mutants
      were generated following gamma-radiation treatment and among these mutants, ph140
      was found to be the most sensitive to phleomycin. Molecular analysis revealed
      that the mutant ph140 harbored a mutation in the DNA repair gene RAD6. Moreover,
      a functional copy of the RAD6 gene restored full phleomycin resistance to strain
      ph140. Our findings indicate that the RAD6 protein is essential for yeast
      cellular resistance to phleomycin.

PMID- 8989865
TI  - Nucleotide sequence, insertional mutagenesis, and transcriptional mapping of a
      conserved region of the baculovirus Autographa californica nuclear polyhedrosis
      virus (map unit 64.8-66.9).
AB  - The nucleotide sequence of a 2773-bp region of the Autographa californica nuclear
      polyhedrosis virus HR3 variant (AcMNPV) (map unit 64.4-68.2) has been determined.
      This region lies between the previously analyzed p6.9 and p80 genes. Three open
      reading frames were contained within this region, potentially coding for proteins
      of 45, 40, and 12 kDa. The 5' ends of transcripts capable of coding for the 45-
      and 12-kDa proteins map to consensus baculovirus late transcription start sites
      (ATAAG), while the major 5' end of the transcript coding for the 40-kDa protein
      maps 16 nucleotides downstream from another late transcription start site
      sequence, GTAAG. Attempts to prepare recombinant viruses containing insertions
      within these three genes were negative, suggesting that they are all essential
      for virus replication in cell culture. The size and organization of transcripts
      expressed from this region of AcMNPV were very similar to those of the previously
      described homologous region of Orgyia pseudotsugata nuclear polyhedrosis virus
      (OpMNPV). The three AcMNPV protein sequences (p45, p40, and p12) showed amino
      acid sequence homology with the proteins p48, p45, and p12 of OpMNPV, suggesting
      this region is highly conserved in baculoviruses.

PMID- 8989866
TI  - Tn5431 arose by transposition of Tn3 into Tn1721.
AB  - To further characterize Tn5431, which is composed of Tn3 and Tn1721, DNA
      sequencing was carried out. It was demonstrated that Tn5431 arose by
      transposition of Tn3 into Tn1721. Multiple mutations in the Tn3 tnpA gene have
      occurred, rendering the Tn3 portion of Tn5431 transposition defective and
      ensuring the simultaneous transposition of the antibiotic resistance determinants
      on Tn3 and Tn1721.

PMID- 8989867
TI  - Production of lactones and peroxisomal beta-oxidation in yeasts.
AB  - Among aroma compounds interesting for the food industry, lactones may be produced
      by biotechnological means using yeasts. These microorganisms are able to
      synthesize lactones de novo or by biotransformation of fatty acids with higher
      yields. Obtained lactone concentrations are compatible with industrial
      production, although detailed metabolic pathways have not been completely
      elucidated. The biotransformation of ricinoleic acid into gamma-decalactone is
      taken here as an example to better understand the uptake of hydroxy fatty acids
      by yeasts and the different pathways of fatty acid degradation. The localization
      of ricinoleic acid beta-oxidation in peroxisomes is demonstrated. Then the
      regulation of the biotransformation is described, particularly the induction of
      peroxisome proliferation and peroxisomal beta-oxidation and its regulation at the
      genome level. The nature of the biotransformation product is then discussed (4
      hydroxydecanoic acid or gamma-decalactone), because the localization and the
      mechanisms of the lactonization are still not properly known. Lactone production
      may also be limited by the degradation of this aroma compound by the yeasts which
      produced it. Thus, different possible ways of modification and degradation of
      gamma-decalactone are described.

PMID- 8989868
TI  - Electroporation of cell membranes: a review.
AB  - The study of the electroporation on biomembranes has become one of the most
      exciting topics in the biophysical and biotechnological areas. Researchers all
      over the world have been focused on four major areas: measurements of
      transmembrane potential (TMP); dynamics of electroporation such as time sequence,
      properties of electropores such as size, structure, and population; membrane
      permeabilization and breakdown theory; and the effects of secondary factors such
      as ions type and cell growth stage on electroporation. This article reviews some
      of the recent discoveries and theories on this subject. Studies on TMP and pore
      dynamics remain a difficult task. Since the area of electroporation on a
      biomembrane is small (less than 0.1% of total surface area) and the time sequence
      of electropores is in the submicrosecond range measuring devices with subtle
      detection and time resolution are required. While more and more studies have
      shown the formation sequence of electropore(s) at specific locations on various
      biomembranes, the pore(s) widening process and the subsequent membrane breakdown
      mechanisms remain controversial. The influence of electromechanical stress or
      transmembrane potential on membrane discharge and rupture seems to be a function
      of various factors such as membrane properties, external medium, and the
      protocols of electroporators.

PMID- 8989869
TI  - Simultaneous solid-phase extraction and gas chromatographic-mass spectrometric
      determination of hemoglobin adducts from tobacco-specific nitrosamines and
      aromatic amines.
AB  - A new method for the simultaneous determination of hemoglobin adducts from
      aromatic amines and tobacco-specific nitrosamines (TSNA) is described. After mild
      base-catalysed hydrolysis releasing aromatic amines and the TSNA adduct 4-hydroxy
      1-(3-pyridyl)-1-butanone (HPB), the extraction, cleanup, and concentration are
      performed by a one-step procedure using C18 cartridges. Determination in the
      picograms per gram of hemoglobin range by gas chromatography-mass spectrometry
      with negative chemical ionization requires a separate derivatization procedure
      with pentafluoropropionic anhydride and pentafluorobenzoylchloride for aromatic
      amines and HPB, respectively. The method is shown to be quantitative,
      reproducible, and applicable to the determination of hemoglobin adducts from
      monocyclic and bicyclic aromatic amines as well as TSNA in smokers and
      nonsmokers.

PMID- 8989870
TI  - Supercritical fluid extraction of sulphamethazine and its metabolites from meat
      tissues.
AB  - An investigation is reported of factors affecting the supercritical fluid
      extraction of sulphamethazine and five of its metabolites from spiked meat (swine
      liver and kidney). The addition of the polar modifier methanol to the carbon
      dioxide extracting fluid was found to generally enhance recoveries under
      subcritical and supercritical conditions. Recoveries of the ionic metabolites
      were increased by up to 72% when employing tetramethylammonium hydroxide for ion
      pairing in situ with the supercritical fluid extraction. Extraction efficiency is
      demonstrated to be dependent on the matrix. Extractions of the less polar
      compounds from the kidney are more successful than from the liver, which
      corresponds to their partitioning into the supercritical fluid and/or the greater
      fraction of highly extractable fatty materials. The kidney was more retentive
      than liver for the relatively more polar compounds, which suggests that the liver
      offers a less polar environment under the same extraction conditions.

PMID- 8989871
TI  - Determination of anabolic steroids by HPLC with UV-vis-particle beam mass
      spectrometry.
AB  - This paper describes a general screening method for the determination of anabolic
      steroids in oil-based injectables, water suspensions, dietary supplements, and
      herbal drugs marketed in the form of capsules or tablets. The compounds are
      extracted into methanol, separated on a reversed-phase column with an
      acetonitrile-water gradient, and detected by using an ultraviolet visible (UV
      vis) photodiode array detector and a particle beam mass spectrometric detector
      coupled in series. Identification is based on retention time, UV-vis spectra, and
      mass spectra. Mass spectral confirmation is accomplished by matching with a
      standard when available and by comparison with an electron impact mass spectra
      library that is either commercially available or generated in our laboratory. The
      tandem arrangement of the detectors provides qualitative and quantitative
      information from a single experiment by fully utilizing the inherent advantages
      associated with each detector. This method is applicable to all the anabolic
      steroids encountered in this laboratory so far.

PMID- 8989872
TI  - Ontogeny and limb bone scaling in two New World Marsupials, monodelphis domestica
      and Didelphis virginiana.
AB  - This study examines the growth of two species of marsupials who share common
      ancestry and are born at the same neonatal size of a little less than 1 g.
      Despite this similarity at birth, adult size of these two species differs by
      about 50 times, with the smaller species believed to be the more ancestral. We
      quantified the growth in the limb bones (humerus, femur, ulna, tibia, metacarpal,
      and metatarsal) beginning around 40 days of age until adult size was reached.
      Results indicate that the larger species grows at a higher rate of growth as well
      as for a longer period of time to reach its larger adult size. Despite these
      differences in growth, there were few differences observed in the scaling over
      time of length to width in the various limb bones that were measured. The two
      species, although different in their adult size and the patterns of growth,
      maintain the same length to width proportions in each limb bone. The biggest
      difference between species in scaling was observed in the bones of the hands and
      feet, which may suggest adaptation to size and/or locomotor performance as body
      size increases. Despite variation in size, these heterochronic patterns do not
      affect the shape among adults or over evolutionary time.

PMID- 8989873
TI  - Comparative functional morphology of mandibular forward movement during
      mastication of two murid rodents, Apodemus speciosus (Murinae) and Clethrionomys
      rufocanus (Arvicolinae).
AB  - The anatomy of the masticatory apparatus, the direction in which masticatory
      muscles act during mastication, and jaw muscle forces as estimated by muscle dry
      weight are compared between two murid rodents, the Japanese field mouse (Apodemus
      speciosus, subfamily Murinae) and the gray red-backed vole (Clethrionomys
      rufocanus; subfamily Arvicolinae). The occlusal forces exerted by the deep
      masseter and the anterior temporalis are large in C. rufocanus. Furthermore, in
      this species, the angle between the sagittal plane and the occlusal plane of the
      cheek teeth is larger than in A. speciosus. Therefore, a relatively large
      occlusal force can be generated in C. rufocanus. The estimated line of action of
      the anterior temporalis differs markedly between these two species. The
      functional significance of this difference is discussed relative to the adaptive
      dental characteristics for food processing, the forces required to masticate
      different types of food, and the forces that control mandibular forward movement.

PMID- 8989874
TI  - Detection of sugar residues in rabbit embryo teeth with lectin-horseradish
      peroxidase conjugate: II. A light microscopal study.
AB  - The cellular distribution and changes of sugar residues during tooth development
      in embryos of the rabbit Oryctolagus cuniculus were investigated by using
      horseradish peroxidase-conjugated lectins (lectin-HRP). The lectins SBA, ECA, and
      LTA show no binding to any region of the dental cap and bell stages, whereas BS-1
      and UEA-1 bind to dental cells at both stages. Appropriate control studies
      confirmed the specificity of the binding of the lectins. At cap stage, the
      lectins BS-1 and UEA-1 show moderate binding to the (pre)-ameloblast and (pre)
      odontoblast cells. These results suggest that the acetylgalactosamine and alpha-L
      fucose residues present in (pre)-ameloblasts and (pre)-odontoblasts,
      respectively, are common to determined but relatively undifferentiated cells
      capable of forming matrices of hard tissues. Since the odontoblast and ameloblast
      express dentin and enamel, respectively, it can be speculated that the abundance
      of these residues in these cells might be associated with the maintenance of the
      capacity of the cells to produce such matrices. At the bell stage, the
      odontoblasts display considerable amounts of alpha-L-fucose, whereas alpha-L
      fucose is poorly localized in ameloblasts. However, ameloblasts contain
      significant quantities of N-acetylgalactosamine, whereas only a diffuse
      positivity for this carbohydrate is apparent in odontoblasts. The marked changes
      of the glycosylation pattern of these glycoconjugates might indicate that they
      play a role during the cell-to-cell interaction and might also be involved in the
      odontoblastic and ameloblastic functional activity. Such a possibility is
      entirely speculative until specific in vitro experiments are conducted.

PMID- 8989875
TI  - Immunohistochemical identification of pancreatic hormones, neuropeptides and
      cytoskeletal proteins in pancreas of the camel (Camelus dromedarius).
AB  - The patterns of distribution of insulin (INS), glucagon (GLU), atrial natriuretic
      peptide (ANP), neuropeptide-Y (NPY), cholecystokinin-octapeptide (CCK-8),
      neurofilament-200 protein (NF), S-100 protein (S-100), and vimentin (VIM) in the
      pancreas of the one-humped camel (Camelus dromedarius) were investigated using
      immunohistochemical techniques. INS-immunoreactive cells were observed in the
      central and peripheral parts of the islets of Langerhans, but some solitary INS
      positive cells were found outside the islets. INS-positive cells constituted
      44.26-90.91% [mean +/- standard deviation (std): 67.34 +/- 14.20] of the total
      number of islet cells. GLU-immunopositive cells were located mainly in the
      peripheral region of the islets, and they constituted 11.43-44.44% [mean +/- std:
      23.54 +/- 8.27] of the total number of islet cells. ANP and CCK-8
      immunoreactivity was observed in neurons and perivascular nerves fibers. NPY was
      identified in pancreatic neurons and in some peripheral and central cells of the
      islets of Langerhans. VIM immunoreactivity was observed in the endothelial cells
      of blood vessels and the nerves located in the perivascular, interlobular and
      periacinar regions. VIM was also detected immunohistochemically in the periductal
      nerves of the pancreas. NF occurred only in nerves. S-100 was discerned mainly in
      the nerves of the interlobular connective tissue and in nerves lying close to
      blood vessels and acinar tissue. It is concluded that INS, GLU, ANP, NPY, CCK-8,
      NF, S-100, and VIM are well distributed in the pancreas of the camel.

PMID- 8989876
TI  - Identification of a meristem L1 layer-specific gene in Arabidopsis that is
      expressed during embryonic pattern formation and defines a new class of homeobox
      genes.
AB  - Homeobox genes are master regulatory genes that specify the body plan and control
      development of many eukaryotic organisms, including plants. We isolated and
      characterized a cDNA designated ATML1 (for Arabidopsis thaliana meristem L1
      layer) that encodes a novel homeodomain protein. The ATML1 protein shares high
      sequence homology inside and outside of the homeodomain with both the
      Phalaenopsis O39 and the Arabidopsis GLABRA2 (GL2) homeodomain proteins, which
      together define a new class of plant homeodomain-containing proteins, designated
      HD-GL2. The ATML1 gene was first expressed in the apical cell after the first
      asymmetric division of the zygote and continued to be expressed in all proembryo
      cells until the eight-cell stage. In the 16-cell proembryo, the ATML1 gene showed
      a distinct pattern of expression, with its mRNA becoming restricted to the
      protoderm. In the torpedo stage of embryo development, ATML1 mRNA disappeared
      altogether but reappeared later only in the L1 layer of the shoot apical meristem
      in the mature embryo. After germination, this L1 layer-specific pattern of
      expression was maintained in the vegetative shoot apical meristem, inflorescence,
      and floral meristems, as well as in the young floral organ primordia. Finally,
      ATML1 mRNA accumulated in the protoderm of the ovule primordia and integuments
      and gradually became restricted in its expression to the endothelium surrounding
      the embryo sac. We propose that ATML1 may be involved in setting up morphogenetic
      boundaries of positional information necessary for controlling cell specification
      and pattern formation. In addition, ATML1 provides an early molecular marker for
      the establishment of both apical-basal and radial patterns during plant
      embryogenesis.

PMID- 8989878
TI  - CHL1 encodes a component of the low-affinity nitrate uptake system in Arabidopsis
      and shows cell type-specific expression in roots.
AB  - The Arabidopsis CHL1 (AtNRT1) gene confers sensitivity to the herbicide chlorate
      and encodes a nitrate-regulated nitrate transporter. However, how CHL1
      participates in nitrate uptake in plants is not yet clear. In this study, we
      examined the in vivo function of CHL1 with in vivo uptake measurements and in
      situ hybridization experiments. Under most conditions tested, the amount of
      nitrate uptake by a chl1 deletion mutant was found to be significantly less than
      that of the wild type. This uptake deficiency was reversed when a CHL1 cDNA clone
      driven by the cauliflower mosaic virus 35S promoter was expressed in transgenic
      chl1 plants. Furthermore, tissue-specific expression patterns showed that near
      the root tip, CHL1 mRNA is found primarily in the epidermis, but further from the
      root tip, the mRNA is found in the cortex or endodermis. These results are
      consistent with the involvement of CHL1 in nitrate uptake at different stages of
      root cell development. A functional analysis in Xenopus oocytes indicated that
      CHL1 is a low-affinity nitrate transporter with a K(m) value of approximately 8.5
      mM for nitrate. This finding is consistent with the chlorate resistance phenotype
      of chl1 mutants. However, these results do not fit the current model of a single,
      constitutive component for the low-affinity uptake system. To reconcile this
      discrepancy and the complex uptake behavior observed, we propose a "two-gene"
      model for the low-affinity nitrate uptake system of Arabidopsis.

PMID- 8989877
TI  - The sink-specific and stress-regulated Arabidopsis STP4 gene: enhanced expression
      of a gene encoding a monosaccharide transporter by wounding, elicitors, and
      pathogen challenge.
AB  - A cDNA for the Arabidopsis STP4 gene (for sugar transport protein 4) was
      isolated, and the properties of the encoded protein were studied in
      Schizosaccharomyces pombe. The STP4 monosaccharide H+ symporter is composed of
      514 amino acids and has a calculated molecular mass of 57.1 kD. RNA gel blot
      analyses revealed that STP4 is expressed primarily in roots and flowers of
      Arabidopsis. This was shown in more detail with STP4 promoter-beta-glucuronidase
      (GUS) plants yielding strong STP4-driven GUS activity in root tips and anthers.
      Wounding of plants transformed with STP4-GUS constructs resulted in a rapid
      increase in GUS activity in cells directly adjacent to the lesion. This was
      confirmed by RNase protection analyses in Arabidopsis wild-type plants showing a
      strong, wound-induced increase in STP4 mRNA levels. STP4 expression was induced
      rapidly in suspension-cultured Arabidopsis cells that were treated with the
      Pseudomonas syringae elicitor or with chitin or in Arabidopsis plants that were
      exposed to fungal attacks. Our data suggest that the role of STP4 is to catalyze
      monosaccharide import into classic sinks, such as root tips and anthers, and,
      most importantly, to meet the increased carbohydrate demand of cells responding
      to environmental stress.

PMID- 8989879
TI  - PK12, a plant dual-specificity protein kinase of the LAMMER family, is regulated
      by the hormone ethylene.
AB  - The ethylene signal is transduced in plant cells via phosphorylation events. To
      identify protein kinases whose levels of expression are modulated by the plant
      hormone ethylene, we utilized a differential reverse transcriptase-polymerase
      chain reaction approach using mRNA extracted from ethylene-treated and untreated
      tobacco leaves. An ethylene-induced cDNA clone, PK12, encoding a protein kinase,
      was isolated. PK12 is a new member of the recently defined LAMMER family of
      protein kinases, which has been identified in mammals, flies, yeasts, and plants.
      The LAMMER kinases are related to the cell cycle-dependent CDC2-type kinases and
      are characterized by their similarity at kinase subdomain X. The recombinant PK12
      protein autophosphorylates in vitro on serine, threonine, and tyrosine residues,
      thereby making it a member of the dual-specificity protein kinases.
      Immunoprecipitation of PK12 from plant extracts and kinase assay revealed that
      the apparent PK12 activity is rapidly and transiently increased when plants are
      treated with ethylene. By using in situ hybridization, we detected accumulation
      of the PK12 transcript in leaves after ethylene treatment and in the untreated
      flower abscission zone. The tissue in this zone is known to constitutively
      express ethylene-regulated genes.

PMID- 8989880
TI  - Coordinate regulation of the tryptophan biosynthetic pathway and indolic
      phytoalexin accumulation in Arabidopsis.
AB  - Little is known about the mechanisms that couple regulation of secondary
      metabolic pathways to the synthesis of primary metabolic precursors. Camalexin,
      an indolic secondary metabolite, appears to be the major phytoalexin in
      Arabidopsis. It was previously shown that camalexin accumulation is caused by
      infection with plant pathogens, by abiotic elicitors, and in spontaneous lesions
      in the accelerated cell death mutant acd2. We demonstrate that the accumulation
      of this phytoalexin is accompanied by the induction of the mRNAs and proteins for
      all of the tryptophan biosynthetic enzymes tested. A strong correlation was
      observed between the magnitude of camalexin accumulation and the induction of
      tryptophan biosynthetic proteins, indicating coordinate regulation of these
      processes. Production of disease symptoms is not sufficient for the response
      because systemic infection with cauliflower mosaic virus or cucumber mosaic virus
      did not induce the tryptophan pathway enzymes or camalexin accumulation.
      Salicylic acid appears to be required, but unlike other documented pathogenesis
      related proteins, it is not sufficient for the coordinate induction. Results with
      trp mutants suggest that the tryptophan pathway is not rate limiting for
      camalexin accumulation. Taken together, these results are consistent with the
      hypothesis that the regulation of the tryptophan pathway in plants responds to
      needs for biosynthesis of secondary metabolites.

PMID- 8989881
TI  - Calcium and calmodulin are involved in blue light induction of the gsa gene for
      an early chlorophyll biosynthetic step in Chlamydomonas.
AB  - The Chlamydomonas reinhardtii nuclear gene gsa, which encodes the early
      chlorophyll biosynthetic enzyme glutamate 1-semialdehyde aminotransferase (GSAT),
      is specifically induced by blue light in cells synchronized in a 12-hr-light and
      12-hr-dark regime. Light induction required the presence of a nitrogen source in
      the incubation medium. Maximal induction also required acetate. However, in the
      absence of acetate, partial induction occurred when Ca2+ was present in the
      medium at concentrations of > or = 1 microM. The Ca2+ channel-blocking agents
      Nd3+ and nifedipine partially inhibited the external Ca(2+)-supported induction
      of GSAT mRNA but did not inhibit acetate-supported induction. The calmodulin
      antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide inhibited both external Ca(2+)-supported and acetate
      supported induction. The Ca2+ ionophore A23187 caused a transient induction in
      the dark. These results suggest that Ca2+ and calmodulin are involved in the
      signal transduction pathway linking blue light perception to the induction of
      GSAT mRNA. The electron transport uncoupler carbonyl cyanide m
      chlorophenylhydrazone inhibited acetate-supported induction of GSAT mRNA but did
      not inhibit external Ca(2+)-supported induction. It is proposed that in the
      presence of acetate, an internal pool of Ca2+ can be mobilized as a second
      message, whereas in the absence of acetate, internal Ca2+ is not available but
      the requirement for Ca2+ can be partially met by an external Ca2+ source. The
      mobilization of internal Ca2+ may require energy derived from metabolism of
      acetate.

PMID- 8989882
TI  - Characterization of a novel arginine/serine-rich splicing factor in Arabidopsis.
AB  - Many splicing factors in vertebrate nuclei belong to a class of evolutionarily
      conserved proteins containing arginine/serine (RS) or serine/arginine (SR)
      domains. Previously, we demonstrated the existence of SR splicing factors in
      plants. In this article, we report on a novel member of this splicing factor
      family from Arabidopsis designated atRSp31. It has one N-terminal RNA recognition
      motif and a C-terminal RS domain highly enriched in arginines. The RNA
      recognition motif shows significant homology to all animal SR proteins identified
      to date, but the intermediate region does not show any homology to any other
      known protein. Subsequently, we characterized two cDNAs from Arabidopsis that are
      highly homologous to atRSp31 (designated atRSp35 and atRSp41). Their deduced
      amino acid sequences indicate that these proteins constitute a new family of RS
      domain splicing factors. Purified recombinant atRSp31 is able to restore splicing
      in SR protein-deficient human S100 extracts. This indicates that atRSp31 is a
      true plant splicing factor and plays a crucial role in splicing, similar to that
      of other RS splicing factors. All of the three genes are differentially expressed
      in a tissue-specific manner. The isolation of this new plant splicing factor
      family enlarges the essential group of RS domain splicing factors. Furthermore,
      because no animal equivalent to this protein family has been identified to date,
      our results suggest that these proteins play key roles in constitutive and
      alternative splicing in plants.

PMID- 8989883
TI  - Cloning of a cDNA encoding a plasma membrane-associated, uronide binding
      phosphoprotein with physical properties similar to viral movement proteins.
AB  - Oligogalacturonides are structural and regulatory homopolymers from the
      extracellular pectic matrix of plants. In vitro micromolar concentrations of
      oligogalacturonates and polygalacturonates were shown previously to stimulate the
      phosphorylation of a small plasma membrane-associated protein in potato.
      Immunologically cross-reactive proteins were detected in plasma membrane-enriched
      fractions from all angiosperm subclasses in the Cronquist system.
      Polygalacturonate-enhanced phosphorylation of the protein was observed in four of
      the six dicotyledon subclasses but not in any of the five monocotyledon
      subclasses. A cDNA for the protein was cloned from potato. The deduced protein is
      extremely hydrophilic and has a proline-rich N terminus. The C-terminal half of
      the protein was predicted to be a coiled coil, suggesting that the protein
      interacts with other macromolecules. The recombinant protein was found to bind
      both simple and complex galacturonides. The behavior of the protein suggests
      several parallels with viral proteins involved in intercellular communication.

PMID- 8989884
TI  - Interactions across exons can influence splice site recognition in plant nuclei.
AB  - In vivo analyses of cis-acting sequence requirements for pre-mRNA splicing in
      tobacco nuclei have previously demonstrated that the 5' splice sites are selected
      by their position relative to AU-rich elements within plant introns and by their
      degree of complementarity to the U1 small nuclear RNA. To determine whether the
      presence of adjacent introns affects 5' splice site recognition in plant nuclei,
      we have analyzed the in vivo splicing patterns of two-intron constructs
      containing 5' splice site mutations in the second intron. These experiments
      indicated that the splice site selection patterns in plant nuclei are defined
      primarily by sequences within the intron (intron definition) and secondarily by
      weak interactions across exons (exon definition). The effects of these secondary
      interactions became evident only when mutations in the downstream 5' splice site
      decreased its functionality and differed depending on the availability of cryptic
      splice sites close to the mutant site. In beta-conglycinin chimeric transcripts
      containing multiple cryptic 5' splice sites, the presence of an intact upstream
      intron significantly increased splicing at the downstream 5' splice sites in a
      polar fashion without activating exon skipping. In a natural beta-conglycinin
      transcript, which does not contain cryptic 5'splice sites, mutation of the first
      nucleotide of the downstream intron activated an array of noncanonical 5' and 3'
      splice sites and some exon skipping.

PMID- 8989885
TI  - Pathogen-induced systemic activation of a plant defensin gene in Arabidopsis
      follows a salicylic acid-independent pathway.
AB  - A 5-kD plant defensin was purified from Arabidopsis leaves challenged with the
      fungus Alternaria brassicicola and shown to possess antifungal properties in
      vitro. The corresponding plant defensin gene was induced after treatment of
      leaves with methyl jasmonate or ethylene but not with salicylic acid or 2,6
      dichloroisonicotinic acid. When challenged with A. brassicicola, the levels of
      the plant defensin protein and mRNA rose both in inoculated leaves and in
      nontreated leaves of inoculated plants (systemic leaves). These events coincided
      with an increase in the endogenous jasmonic acid content of both types of leaves.
      Systemic pathogen-induced expression of the plant defensin gene was unaffected in
      Arabidopsis transformants (nahG) or mutants (npr1 and cpr1) affected in the
      salicylic acid response but was strongly reduced in the Arabidopsis mutants eln2
      and col1 that are blocked in their response to ethylene and methyl jasmonate,
      respectively. Our results indicate that systemic pathogen-induced expression of
      the plant defensin gene in Arabidopsis is independent of salicylic acid but
      requires components of the ethylene and jasmonic acid response.

PMID- 8989886
TI  - The maize gamma-zein sequesters alpha-zein and stabilizes its accumulation in
      protein bodies of transgenic tobacco endosperm.
AB  - Zeins are seed storage proteins that form accretions called protein bodies in the
      rough endoplasmic reticulum of maize endosperm cells. Four types of zeins, alpha,
      beta, gamma, and delta, aggregate in a distinctive spatial pattern within the
      protein body. We created transgenic tobacco plants expressing alpha-zein, gamma
      zein, or both to examine the interactions between these proteins leading to the
      formation of protein bodies in the endosperm. Whereas gamma-zein accumulated in
      seeds of these plants, stable accumulation of alpha-zein required simultaneous
      synthesis of gamma-zein. The zein proteins formed accretions in the endoplasmic
      reticulum similar to those in maize endosperm. Protein bodies were also found in
      protein storage vacuoles. The accumulation of both types of zeins peaked early in
      development and declined during maturation. Even in the presence of gamma-zein,
      there was a turnover of alpha-zein, suggesting that the interaction between the
      two proteins might be transitory. We suggest that gamma-zein plays an important
      role in protein body formation and demonstrate the utility of tobacco for
      studying interactions between different zeins.

PMID- 8989887
TI  - UV-B, UV-A, and blue light signal transduction pathways interact synergistically
      to regulate chalcone synthase gene expression in Arabidopsis.
AB  - UV and blue light stimulate transcription of key flavonoid biosynthesis genes in
      a range of higher plants. Here, we provide evidence that several distinct
      "inductive" and "synergistic" UV/blue phototransduction pathways regulate
      chalcone synthase (CHS) gene transcription and transcript accumulation in
      Arabidopsis leaf tissue. Experiments with the long-hypocotyl hy4-2.23N mutant
      showed that separate inductive pathways mediate responses to UV-B and UV-A/blue
      light. Only the UV-A/blue light induction of CHS expression involved the CRY1
      photoreceptor. In addition, UV-A and blue light each act synergistically with UV
      B to stimulate CHS transcript accumulation and beta-glucuronidase activity driven
      by a CHS promoter in transgenic leaf tissue. The UV-A and blue phototransduction
      pathways responsible for synergism are distinct because they produce transient
      and relatively stable signals, respectively, and can function additively to
      stimulate CHS promoter function. The hy4-2.23N mutant retains the synergistic
      interactions between UV-B and both UV-A and blue light, indicating that neither
      synergism pathway involves the CRY1 photoreceptor. Our findings reveal
      considerable complexity in both photoreception and signal transduction in
      regulating CHS gene expression by UV and blue light.

PMID- 8989888
TI  - Molecular characterization of the S locus in two self-incompatible Brassica napus
      lines.
AB  - In Brassica species, self-incompatibility has been mapped genetically to a single
      chromosomal location. In this region, there are two closely linked genes coding
      for the S locus glycoprotein (SLG) and S locus receptor kinase (SRK). They appear
      to comprise the pistil component of the self-incompatibility reaction. SLG and
      SRK are thought to recognize an unknown pollen component on the incompatible
      pollen, and the gene encoding this pollen component must also be linked to the
      SLG and SRK genes. To further our understanding of self-incompatibility, the
      chromosomal region carrying the SLG and SRK genes has been studied. The physical
      region between the SLG-910 and the SRK-910 genes in the Brassica napus W1 line
      was cloned, and a search for genes expressed in the anther revealed two
      additional S locus genes located downstream of the SLG-910 gene. Because these
      two genes are novel and are conserved at other S alleles, we designated them as
      SLL1 and SLL2 (for S locus-linked genes 1 and 2, respectively). The SLL1 gene is
      S locus specific, whereas the SLL2 gene is not only present at the S locus but is
      also present in other parts of the genomes in both self-incompatible and self
      compatible Brassica ssp lines. Expression of the SLL1 gene is only detectable in
      anthers of self-incompatible plants and is developmentally regulated during
      anther development, whereas the SLL2 gene is expressed in anthers and stigmas in
      both self-incompatible and self-compatible plants, with the highest levels of
      expression occurring in the stigmas. Although SLL1 and SLL2 are linked to the S
      locus region, it is not clear whether these genes function in self
      incompatibility or serve some other cellular roles in pollen-pistil functions.

PMID- 8989890
TI  - Biomarkers of heavy metal reproductive effects and interaction with essential
      elements in experimental studies on female rats.
AB  - Experimental studies in laboratories in Croatia and U.S.A. were conducted on
      female rats exposed to lead or cadmium to evaluate effects on the female
      reproductive integrity. The health condition of the offspring and relationship
      with essential elements were also evaluated. By using simple biomarkers of
      reproductive effects it was found that subchronic oral exposure to lead (1500
      5500 ppm) or cadmium (50 ppm) during pregnancy and lactation decreased pup body
      weight, and that lead also decreased pup viability. Acute exposure to cadmium (3
      or 5 mg/kg body weight s.c.) in vivo suppressed serum concentrations of
      progesterone and estradiol depending on the reproductive stage. Organ
      accumulations of lead or cadmium were accompanied by changes in the
      concentrations of iron and zinc in both mother and pups. Future research should
      focus on the effects of metals on endocrine disruption in the ovary and placenta,
      and on concomitant interaction of toxic and essential metals in mother and
      offspring.

PMID- 8989891
TI  - Work performance evaluation in patients suffering from hypertension.
AB  - In 41 patients suffering from hypertension blood pressure values obtained in
      routine examinations in an outpatient clinic were analysed by correlating the
      highest values of blood pressure measured using the 24-hour monitoring model
      developed by Holter and those obtained in exertion tests developed by Bruce. The
      correlation coefficients indicated poor correlation. The results proved the
      author's hypothesis that it was not possible to predict blood pressure
      development in 24-hour monitoring based on values of blood pressures obtained in
      routine outpatient practice only nor could these values be used for the
      assessment of work performance. It can be concluded that individual functional
      testing of patients suffering from hypertension is the best method for assessing
      their work performance.

PMID- 8989892
TI  - Computerized estimation of compatibility of stressors at work and worker's health
      characteristics.
AB  - A system of computerized estimation of compatibility of stressors at work and
      worker's health characteristics is presented. Each characteristic is defined and
      scored on a specific scale. Incompatible workplace characteristics as related to
      worker's characteristics are singled out and offered to the user for an ergonomic
      solution. Work on the system started in 1987. This paper deals with the system's
      further development, which involves a larger number of topics, changes of the
      algorithm and presentation of an applicative case. Comparison of the system's
      results with those of medical experts shows that the use of the system tends to
      improve the thoroughness and consistency of incompatibility evaluations and
      consequently to make working ability assessment more objective.

PMID- 8989893
TI  - Deaths of drug addicts in Split.
AB  - Since the beginning of the war in Croatia, the number of drug addicts and of
      fatal intoxications in the Split region has increased. Drug-related fatalities (n
      = 25) were investigated over a 12-month period in 1995. Data about the cause of
      death were based on the information from police reports, autopsy findings and
      toxicological analyses. The main drug involved was heroin. Other drugs were
      rarely reported. Blood tests for alcohol were performed in all cases. Alcohol
      consumption increased the risk of heroin overdosing.

PMID- 8989889
TI  - Protein farnesyltransferase in plants: molecular characterization and involvement
      in cell cycle control.
AB  - Farnesylation is required for membrane targeting, protein-protein interactions,
      and the biological activity of key regulatory proteins, such as Ras small GTPases
      and protein kinases in a wide range of eukaryotes. In this report, we describe
      the molecular identification of a plant protein farnesyltransferase (FTase) and
      evidence for its role in the control of the cell cycle in plants. A pea gene
      encoding a homolog of the FTase beta subunit was previously cloned using a
      polymerase chain reaction-based strategy. A similar approach was used to clone a
      pea gene encoding a homolog of the FTase alpha subunit. The biochemical function
      of the pea FTase homologs was demonstrated by the reconstitution of FTase enzyme
      activity using FTase fusion proteins coexpressed in Escherichia coll. RNA gel
      blot analyses showed that levels of FTase mRNAs are generally higher in tissues,
      such as those of nodules, that are active in cell division. The relationship of
      FTase to cell division was further analyzed during the growth of suspension
      cultured tobacco BY-2 cells. A biphasic fluctuation of FTase enzyme activity
      preceded corresponding changes in mitotic activity at the early log phase of cell
      growth. Moreover, manumycin, a specific inhibitor of FTase, was effective in
      inhibiting mitosis and growth in these cells. Using synchronized BY-2 cells,
      manumycin completely blocked mitosis when added at the early S phase but not when
      added at the G2 phase. These data suggest that FTase is required for the plant
      cell cycle, perhaps by modulating the progression through the S phase and the
      transition from G1 to the S phase.

PMID- 8989894
TI  - Acute cyanide poisoning: clinical spectrum, diagnosis, and treatment.
AB  - Cyanide poisoning presents in many forms. Industrial intoxications occur due to
      extensive use of cyanide compounds as reaction products. Smoke inhalation, a
      polyintoxication, is most often responsible for domestic cyanide poisonings.
      Suicidal poisonings are rare. Cyanogenic compounds may produce acute or subacute
      toxicity. Signs of cyanide poisoning include headache, vertigo, agitation,
      confusion, coma, convulsions and death. Definitive laboratory confirmation is
      generally delayed. Elevated plasma lactate, associated with cardiovascular
      collapse, should suggest cyanide intoxication. Immediate treatment includes 100%
      oxygen, assisted ventilation, decontamination, correction of acidosis and blood
      pressure support. Antidotes include oxygen, hydroxocobalamin, di-cobalt EDTA and
      methaemoglobin-inducers. Hydroxocobalamin is an attractive antidote due to its
      rapid cyanide binding and its lack of serious side-effects, even in the absence
      of cyanide intoxication. Sodium thiosulphate acts more slowly than other
      antidotes and is indicated in subacute cyanogen poisoning and as an adjunct to
      acute cyanide poisoning. Initial evaluation of antidotal efficacy is based on
      correction of hypotension and lactic acidosis; the final analysis rests on the
      degree of permanent central nervous system injury.

PMID- 8989895
TI  - Genetic exchange in trypanosomes.
AB  - The process of genetic exchange in trypanosomes was first described 10 years ago,
      when Jenni and colleagues obtained hybrid trypanosomes after cotransmitting 2
      Trypanosoma brucei ssp. clones through the tsetse fly. The process is a non
      obligatory part of the trypanosome life cycle and takes place in the fly,
      probably during development in the salivary glands. Nuclear DNA markers are
      inherited for the most-part in a mendelian fashion, indicating that meiosis is
      involved. However, there is no evidence for haploid gametes. Analysis of the
      inheritance of kinetoplast DNA, the trypanosome's mitochondrial DNA, indicates
      that trypanosome mitochondria fuse during genetic exchange, allowing parental
      kDNAs to mix. Population genetics analysis of natural T. brucei ssp. provides
      little support for random or widespread mating in the wild. However, even very
      rate mating events, by mobilising genes for drug resistance, virulence or human
      infectivity into other genetic backgrounds, could have implications for the
      generation of epidemics.

PMID- 8989896
TI  - 26th Congress of the International Society of Haematology. Singapore, 25-29
      August 1996. Abstracts.

PMID- 8989897
TI  - Traumatic arteriovenous fistula. Case report and overview.
AB  - The difficulties in detecting vascular injuries associated with penetrating limb
      trauma are greater than generally appreciated. Any delay in diagnosis will
      compromise management and potentially may lead amputation. Traumatic
      arteriovenous fistulas (AV fistula) produce several profound pathophysiological
      and structural changes in the circulatory dynamic of the vessel associated with
      fistula. Most of the changes are reversible after surgery. However, in
      longstanding AV fistulas, irreversible degenerative changes occur in the arterial
      wall and result in dilation and thrombosis. This can make late closure
      technically difficult. This report presents a case of a femoral AV fistula
      persisting for three years durations.

PMID- 8989898
TI  - Children's conflict-related emotions: implications for morality and autonomy.

PMID- 8989899
TI  - Autonomy and goal attainment: parenting, gender, and children's social
      competence.

PMID- 8989900
TI  - Thrombopoietin: the primary regulator of megakaryocytopoiesis and thrombopoiesis.

PMID- 8989901
TI  - Cell cycle modulation by hematopoietic growth factors in myelodysplastic
      syndromes: analysis by three-color flow cytometry.
AB  - Investigations of the effects of hematopoietic growth factors (HGFs) on the cell
      cycle of cells from myelodysplastic syndrome (MDS) have been hampered by
      technical difficulties. In this study, using a recently established flow
      cytometric method that enables detailed analysis of the cell cycle (Gzero-, G1-,
      S-, and G2/M-phases) of target cells in a heterogeneous cell population, we
      examined the effects of granulocyte colony-stimulating factor (G-CSF) and other
      HGFs on the cell cycle of CD13-positive cells (blasts and other malignant
      myelocytic and monocytic cells) in MDS. The cell cycle response to G-CSF
      (decrease in Gzero-phase cells and increase in S-phase cells) was heterogeneous
      among MDS cases. When the data for 13 MDS cases and 15 de novo AML cases were
      compared statistically, the magnitude of cell cycle activation by G-CSF was
      weaker for the cells from the MDS cases. Stem cell factor, interleukin-3, or a
      combination of these HGFs with G-CSF reduced the Gzero-phase cell percentage in
      all examined MDS cases whose cell cycle was unresponsive to G-CSF alone. When
      cytosine arabinoside was added to cells with or without stimulation by HGFs, the
      viable G0-phase cell count was reduced in HGF-stimulated cells compared with
      unstimulated cells in seven of eight cases. The present results suggest that G
      CSF-induced cell cycle stimulation of malignant cells can be expected in a
      fraction of MDS patients and that even in MDS patients whose cells do not respond
      to G-CSF, employment of other HGFs and their combination with G-CSF is worth
      consideration. The results also suggest that a well-designed therapy using HGFs
      and chemotherapeutic drugs may reduce the quiescent (Gzero) cell count in MDS,
      which is assumed to be responsible for drug resistance derived from cell
      kinetics.

PMID- 8989902
TI  - Osteoclast development from hematopoietic stem cells: apparent divergence of the
      osteoclast lineage prior to macrophage commitment.
AB  - To further clarify the progression of osteoclast development, the relationship of
      clonogenic osteoclast progenitors (CFU-O) to macrophage or more primitive
      progenitors was examined. Serum-free culture supernatant of a tumor clone (CESJ)
      was used as a source of an osteoclast colony stimulating factor (O-CSF). CFU-O
      derived colonies were identified by their characteristic positive staining for
      tartrate resistant acid phosphatase (TRAPase). The effect of macrophage colony
      stimulating factor (M-CSF) and stem cell factor (SCF) on osteoclast progenitors
      was examined by pre-culturing mouse bone marrow (BM) cells in agar medium
      containing M-CSF or SCF and overlaying CESJ medium 0-7 days later. The number of
      TRAPase+ colonies decreased while TRAP- macrophage colonies increased in M-CSF
      pre-cultures as overlays of CESJ medium were delayed. On the other hand, TRAPase+
      and mixed colonies persisted in SCF pre-cultures with CESJ medium overlays.
      Conversely, all colonies were TRAPase+ and no macrophage colonies developed in O
      CSF pre-cultures overlaid with M-CSF. CFU-O, but not CFU-M, survived 7 days
      without exogenous CSFs in agar medium. In fractionated BM, the majority (> 99%)
      of CFU-O were in the c-kit positive population; however, a specific antibody to
      SCF did not affect O-CSF-induced TRAPase+ colony formation, suggesting the
      proliferation and differentiation of osteoclast progenitors are independent of c
      kit-SCF interactions. These studies provide further experimental evidence to
      support the concept that O-CSF acts on progenitors in earlier stages of
      development, supporting their differentiation into the osteoclast lineage prior
      to macrophage commitment.

PMID- 8989903
TI  - Increased neutrophil respiratory burst in myeloproliferative disorders: selective
      enhancement of superoxide release triggered by receptor-mediated agonists and low
      responsiveness to in vitro cytokine stimulation.
AB  - The neutrophil superoxide (O2-)-producing capacity in 57 patients with chronic
      myeloproliferative disorders (MPDs) and eight patients with chronic
      myelomonocytic leukemia (CMML) was investigated. O2- release in neutrophils
      stimulated by chemotactic peptide was markedly increased in all types of chronic
      MPD, including chronic myelogenous leukemia in both chronic phase and blastic
      crisis, polycythemia vera, and essential thrombocythemia, but was normal in CMML,
      which is thought to be a myelodysplastic disorder rather than MPD. Increase in
      O2(-)-producing capacity in MPD was also observed when other receptor-mediated
      agonists such as interleukin-8 and concanavalin A were used, but not when phorbol
      ester, a direct activator of protein kinase C, was used as the triggering agonist
      of O2- release. Priming effects of granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage CSF (GM-CSF), and tumor necrosis factor (TNF) on
      chemotactic peptide-induced O2- release was observed in all patients with MPD and
      CMML, though fold enhancement of priming effects was much less in MPD compared
      with normal subjects. In addition, the priming effects of TNF were less than
      those of GM-CSF in 10 cases, whereas the priming effects of TNF were consistently
      and markedly greater than those of GM-CSF in normal subjects. Tyrosine
      phosphorylation of 42-kDa protein stimulated by G-CSF, GM-CSF, and TNF was
      observed in CML neutrophils to be identical to that in normal neutrophils.
      Present results indicate specific potentiation of the receptor-mediated route of
      signaling that is linked to the respiratory burst and downregulated
      responsiveness to cytokines in neutrophils in patients with all types of chronic
      MPD, suggesting in vivo priming of patient neutrophils via certain mechanism by
      cytokines or related stimuli in these hematological disorders.

PMID- 8989904
TI  - Effects of short-term in vivo administration of G-CSF on bone marrow prior to
      harvesting.
AB  - The brief administration of G-CSF to previously treated solid tumor patients has
      a positive impact on the overall cellularity and progenitor cell content of
      harvested bone marrow. Fifty-seven patients, fully recovered from therapy and
      growth factor support, had approximately 500 mL of steady-state marrow harvested
      as outpatients under local anesthesia. Each patient then received 5 micrograms/kg
      of G-CSF every 12 hours subcutaneously for either 24 hours (21 patients), 36
      hours (20 patients), or 48 hours (16 patients) just before harvesting 500 mL of
      activated bone marrow. Bone marrow cellularity (x 10(6)/mL) increased from a
      steady-state mean of 10.7 (+/- 0.9) to 25.7 (+/- 2.8) after 24 hours, 9.3 (+/-
      0.7) to 29 (+/- 2.5) after 36 hours, and 9.6 (+/- 0.7) to 28.4 (+/- 2.5) after 48
      hours. Although the percentage of CD34+ cells did not significantly change in
      stimulated marrow, the total number of CD34+ cells (x 10(6)) collected increased
      from 34 (+/- 6.3) to 52 (+/- 6.6) after two injections, 28 (+/- 3.6) to 65 (+/-
      8.5) after three injections, and 28 (+/- 5.4) to 75 (+/- 18) after four
      injections of G-CSF. Further phenotyping demonstrated significant increases in
      CD34+HLA-DR+ cells with all three schedules relative to steady-state marrow.
      There were no changes in the total number of CD34+HLA-DR- cells after two and
      four shots; however, this population increased from 10 x 10(6) in steady-state
      marrow to 23 x 10(6) (p = 0.012) after three injections. Analysis of peripheral
      blood indicated a statistically significant increase in the circulating white
      count, but more interestingly, there were significant increases in the number of
      CD34+ cells x 10(4)/mL, suggesting the onset of mobilization. Steady-state blood
      contained a mean of 0.86 x 10(4)/mL CD34+ cells, which increased to 4.37 x
      10(4)/mL, 7.43 x 10(4)/mL, and 8.62 x 10(4)/mL after two, three, and four
      injections, respectively-levels of CD34+ cells that are comparable to steady
      state marrow. Reinfusion of a median of 1.6 x 10(6) activated CD34+ cells/kg
      resulted in the recovery of > 100/mm3 neutrophils and > 20,000 platelets by days
      9 and 19, respectively, which was faster than our previous patients who received
      steady-state marrow, and comparable to our patients who received mobilized
      peripheral stem cells.

PMID- 8989905
TI  - Successful retroviral mediated transduction of a reporter gene in human dendritic
      cells: feasibility of therapy with gene-modified antigen presenting cells.
AB  - In this study we have analyzed the feasibility of gene transfer in human
      dendritic cells (DCs). DCs were generated from T and B cell-depleted peripheral
      blood mononuclear cells cultured for 7 days in the presence of
      granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL
      4). The cells showed morphologic and immunophenotypical features typical of DCs,
      including expression of major histocompatibility complex (MHC) class I and II
      molecules, CD1a, CD80, CD86, CD13, CD33, CD40, and CD54. The cells showed high
      stimulatory activity in both allogeneic and autologous mixed lymphocyte reaction
      (MLR). The bacterial reporter gene lacZ coding for beta-galactosidase (beta-gal)
      was introduced in DCs by three sequential cycles of infection using a MFG
      retroviral vector system. After 7 days of culture 35-67% of the cells showed high
      expression of beta-gal activity, proving successful gene transfer. Stable
      integration of the lacZ gene was demonstrated by genomic DNA-polymerase chain
      reaction (PCR) up to 20 days after gene transfer. The percentage of transduction
      was similar when DCs were further purified by immunomagnetic separation according
      to CD1a-expression. We conclude that human DCs can be efficiently gene modified,
      further broadening the spectrum of possible DC-based clinical applications.

PMID- 8989906
TI  - Tyrosine phosphorylation of the product of the c-cbl protooncogene is [corrected]
      induced after integrin stimulation.
AB  - Integrin crosslinking on human B cells induces tyrosine phosphorylation of a set
      of proteins ranging from 105 to 130 kDa, among which is the focal adhesion kinase
      p125FAK. Here we show that the c-CBL protooncogene product p120c-CBL is a
      component of these substrates. beta 1 integrin stimulation of p120c-CBL
      phosphorylation was observed in both transformed and normal human B cells, and
      was inhibited by prior treatment of cells with cytochalasin B, which disrupts the
      actin network. In contrast, tyrosine phosphorylation of p120c-CBL following
      crosslinking of the B cell antigen receptor (BCR) was not affected by
      cytochalasin B. Integrin stimulation of the promegakaryocytic cell line MO7e also
      led to a cytoskeleton-dependent tyrosine phosphorylation of p120c-CBL. In MO7e
      cells, this stimulation was induced by ligation of either beta 1 or beta 2
      integrin, whereas only by ligation of beta 1 integrin in B cells. Tyrosine
      phosphorylation of p120c-CBL links phosphatidylinositol-3 kinase (PI-3K) with the
      BCR signaling machinery. Although the p85 subunit of PI-3K was increased in p120c
      CBL immunoprecipitates from BCR-stimulated B cells, this association was only
      minimally increased by beta 1 integrin ligation. The function of p120c-CBL
      remains unknown; however, its interactions in vitro and in vivo with Src homology
      2 and 3 (SH2 and SH3) domain-containing proteins suggest that p120c-CBL has a
      significant function in signal transduction pathways, and therefore may play a
      role in integrin signaling in lymphoid and hematopoietic cells.

PMID- 8989907
TI  - Retroviral mediated gene transfer of Flt3 ligand enhances proliferation and MAP
      kinase activity of AML5 cells.
AB  - Flt3/flk-2 ligand (Flt3-L) co-stimulates and synergizes with cytokines such as
      granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating
      factor (G-CSF), interleukin-3 (IL-3), and erythropoietin in the proliferation of
      bone marrow and cord blood hematopoietic stem and progenitor cells. To study the
      biological effects of Flt3-L on the Flt3-L responsive AML5 cell line, the
      retroviral vector L(Flt3-L)SN was constructed based on the vector LXSN, but
      containing the human Flt3-L cDNA transcriptionally regulated by the Mo-MLV LTR.
      High-titer amphotropic producer cells that generated 10(6) cfu/mL after shuttle
      packaging through ecotropic packaging cells were isolated. AML5 cells were
      cultured overnight with L(Flt3-L)SN retroviral supernatant, 8 micrograms/mL
      polybrene, and 100 U/mL G-CSF, and expanded 1 week in medium with G-CSF.
      Transduced cells were selected in medium containing 0.4 mg/mL G418 and then in
      medium with 1.0 mg/mL G418. Retroviral mediated gene transfer in G418-resistant
      cells was confirmed after amplification by PCR of neo-specific sequences in
      genomic DNA. Northern blot analysis demonstrated L(Flt3-L)SN mRNA expression.
      Soluble Flt3-L was undetectable (< 100 pg/mL) by ELISA assay of conditioned
      medium from transduced cells, but Flt3-L was detected on the surface of AML5
      cells by FACS analysis. Cells were plated in colony assay with and without 100
      ng/mL Flt3-L, 100 U/mL G-CSF, and the combination. Gene transfer or growth factor
      treatment increased somewhat the clonogenicity of the nontransduced AML5 cells.
      More strikingly, L(Flt3-L)SN and each growth factor combination greatly increased
      the size of the resultant colonies such that the size of colonies from AML5/Flt3
      L cells without added growth factor approximated that of the AML5 cells
      stimulated by exogenous soluble Flt3-L. Moreover, MAP kinase activity in L(Flt3
      L)SN-transduced cells cultured without soluble Flt3-L was increased to the level
      induced in control cells by soluble Flt3-L. These results indicate that
      retroviral mediated gene transfer and autologous expression of the Flt3-L
      enhances growth and intracellular signaling of AML5 cells, information that
      should be of value for studying the effects of Flt3-L on immature subsets of
      primary hematopoietic stem and progenitor cells.

PMID- 8989908
TI  - Reverse transcriptase-polymerase chain reaction (RT-PCR)-controlled
      immunomagnetic purging of breast cancer cells using the magnetic cell separation
      (MACS) system: a sensitive method for monitoring purging efficiency.
AB  - A modified reverse transcriptase-polymerase chain reaction (RT-PCR) technique was
      established with the aim of monitoring the tumor cell contamination in peripheral
      blood stem cells harvested from breast cancer patients. In an experimental
      approach, single cell suspensions of different breast cancer cell lines were
      mixed to normal peripheral blood mononuclear cells in order to 1) determine the
      sensitivity of tumor cell detection within PBMC and 2) compare polymerase chain
      reaction in its capacity of monitoring the efficiency of immunomagnetic purging
      using the magnetic cell separation (MACS) system to immunocytochemical staining.
      Several target sequences were assessed for their indicative potential and
      specificity allowing the detection of breast cancer cells by RT-PCR. Among the
      sequences evaluated, epithelial growth factor receptor (EGF-R) mRNA and
      Cytokeratin 19 mRNA were shown to be highly specific and sensitive markers for
      the detection of breast cancer cells within normal peripheral blood mononuclear
      cells and for the evaluation of the efficiency in immunomagnetic purging. In
      addition, we were able to show that the MACS is a potent and efficient tool for
      the selection of tumor cells from peripheral blood mononuclear cells, thus
      establishing its value for clinical scale immunomagnetic purging.

PMID- 8989909
TI  - Differentiation of human CD34+CD38- cord blood stem cells into B cell progenitors
      in vitro.
AB  - Umbilical cord blood CD34+CD38- cells are a rare, quiescent, primitive progenitor
      subpopulation lacking expression of lymphoid and myeloid lineage specific
      antigens. Although myeloid, erythroid, and megakaryocytic differentiation from
      these cells has been described, B lineage differentiation has not been
      demonstrated previously. We report here that highly enriched human B cell
      progenitors can be consistently generated from CD34+CD38- cord blood cells using
      long-term culture on the murine stromal line, S17, in the absence of added
      cytokines. After 6-8 weeks, cell numbers increased up to 160-fold, and cultures
      contained > 80-90% CD10+CD19+ B progenitors. Consistent with previous reports
      describing delayed myeloid cell differentiation from CD34+CD38- cells, production
      of B cell progenitors from CD34+CD38- cord blood cells was delayed 2-4 weeks
      relative to cultures initiated with either CD34+CD38bright or CD34+CD38dim
      progenitors. Addition of Flt3 ligand to long-term cultures resulted in a 2-3-fold
      greater increase in the number of CD19+ cells generated after 4-8 weeks. The
      selective outgrowth of B cell progenitors using this culture model will be useful
      for a range of in vitro studies using primitive hematopoietic progenitors.

PMID- 8989910
TI  - Increased manganese superoxide dismutase activity, protein, and mRNA levels and
      concurrent induction of tumor necrosis factor alpha in radiation-initiated Syrian
      hamster cells.
AB  - The levels of the antioxidant enzyme manganese superoxide dismutase (Mn-SOD) are
      frequently decreased in tumor cells and increased in normal cells upon treatment
      with ionizing radiation. We studied Mn-SOD at different stages during the
      neoplastic conversion of radiation-initiated Syrian hamster embryo HDR-3 cells.
      Mn-SOD activity and the concentration of Mn-SOD protein and mRNA increased
      gradually during the malignant transformation of HDR-3 cells after radiation
      exposure; fully neoplastic cells showed greater Mn-SOD levels than preneoplastic
      and normal 84-3 cells. Inhibitors of superoxide (SO) anion production
      (thenoyltrifluoroacetone and rotenone) decreased the concentration of Mn-SOD
      mRNA, raising the possibility that the generation of SO radicals participated in
      the upregulation of Mn-SOD in cells transformed by exposure to radiation. We
      observed an increase in the concentration of tumor necrosis factor alpha (TNF
      alpha) in HDR-3 cells relative to mock-irradiated cells. Together with the
      observation that TNF alpha stimulates the production of SO by mitochondria and
      increases the level of Mn-SOD mRNA in other experimental systems, our results
      suggest that as normal 84-3 cells undergo malignant transformation induced by
      ionizing radiation they produce TNF alpha, to which the cells respond by
      increasing the concentration of Mn-SOD mRNA and protein and the activity of the
      enzyme.

PMID- 8989911
TI  - Lead acetate mutagenicity and mutational spectrum in the hypoxanthine guanine
      phosphoribosyltransferase gene of Chinese hamster ovary K1 cells.
AB  - The molecular nature of lead-induced mutations was examined in this study to more
      thoroughly understand lead mutagenesis. Chinese hamster ovary K1 cells were
      exposed to 0.5-3 mM lead acetate for 24 h. The median lethal dose (LD50) value
      was 1.5 mM, and the hypoxanthine guanine phosphoribosyltransferase (HPRT) mutant
      frequency increased linearly as lead concentrations were raised from 0.5 to 1.5
      mM. We also amplified the HPRT cDNAs of 56 independent lead-induced mutants by
      reverse transcriptase-polymerase chain reaction (PCR). Forty-two mutant cDNAs
      were successfully amplified: 36 mutants had transcripts of normal or slightly
      smaller than normal size, and six mutants had large deletions. The other 14
      mutants whose HPRT cDNA could not be amplified were subjected to genomic-DNA PCR
      analysis. All of those mutants had one or more exons missing from their genomic
      HPRT DNA. DNA sequencing of mutant cDNAs showed that 22 had single-base
      substitutions, four had small alterations, 10 had single-exon deletions, and six
      were missing two or three exons. Furthermore, DNA sequencing of the HPRT intron
      exon boundaries in eight splice mutants revealed that all of them had single-base
      substitutions in their genomic DNA. G.C base substitutions occurred 3.3-fold more
      frequently than A.T base substitutions. Similar frequencies were observed for G.C
      ->A.T, G.C-->T.A, and G.C-->C.G mutations. These results suggest that G.C base
      pairs may be the primary target sites for lead mutagenesis.

PMID- 8989912
TI  - A high-resolution analysis of chromatin structure along p53 sequences.
AB  - A detailed investigation of how nucleosomes are formed and arranged on the DNA
      sequence is a prerequisite to understanding the molecular mechanisms of DNA
      dependent processes such as transcription, replication, DNA repair, and
      mutagenesis. In this report we analyzed the chromatin structure of exons 5-8 of
      the p53 gene in human fibroblasts. We mapped at the nucleotide level the
      positions of DNase I and micrococcal nuclease cleavage sites in permeabilized
      cells. Areas of clear DNase I protection, which would be indicative of the
      binding of sequence-specific proteins, were not detected. Instead, the
      micrococcal nuclease and DNase digestion patterns suggested that this region was
      covered by nucleosomes and that two areas spanning exons 5 and 6 are occupied
      preferentially. These nucleosomes could influence DNA damage distribution, repair
      of certain lesions, and other aspects of the mutagenesis process in p53
      sequences.

PMID- 8989913
TI  - Characterization of mutant HA-ras gene expression in transformed murine
      keratinocyte lines grown under in vitro and in vivo conditions.
AB  - We investigated the Ha-ras and Ki-ras gene status, tumorigenicity, pathology,
      line derivation, and intercellular communication of 7,12
      dimethylbenz[a]anthracene-initiated papilloma-, carcinoma-, and hyperplastic skin
      producing cell lines to further characterize them. Six of nine tumor cell lines
      grown in vitro expressed both mutant and normal Ha-ras proteins, and three lines
      expressed only normal Ha-ras. However, when grown subcutaneously in nude mice,
      seven of the nine lines expressed both mutant and normal Ha-ras, one line
      expressed normal Ha-ras, and one line did not grow subcutaneously. One papilloma
      line, P2/15, appeared to have an inducible mutant Ha-ras gene, as it was
      expressed only in vivo. These findings suggest that mutant Ha-ras genes may be
      lost in only a minor population of tumor lines during growth in culture. Finally,
      we found that mutant Ha-ras gene expression was strongly correlated with
      tumorigenicity in nude mice and that intercellular communication was strongly
      correlated with the derivation of the lines.

PMID- 8989914
TI  - Multifactor regulation of prostaglandin H synthase-2 in murine keratinocytes.
AB  - Prostaglandin H synthase (PGHS) is the rate-limiting enzyme responsible for the
      formation of the prostaglandins from arachidonic acid. Prostaglandins (and other
      metabolites) elicit signals for inflammation, which is thought to be required for
      tumor promotion in the mouse skin carcinogenesis model. This study was designed
      to examine the effect of protein kinase C (PKC)-activating tumor promoters (4
      beta-12-O-tetradecanoylphorbol-13-acetate (TPA)), non-PKC-type promoters
      (anthralin, benzoyl peroxide, okadaic acid), and mitogens (epidermal growth
      factor (EGF)) on the levels of the constitutive (PGHS-1) and inducible (PGHS-2)
      forms of PGHS in murine keratinocytes. Northern analysis of mRNA isolated from
      cultures treated with TPA (1 microgram/mL) showed that a single treatment of TPA
      produced a sevenfold increase in PGHS-2 mRNA by 1 h that decreased by 6 h after
      treatment. PGHS-2 protein levels were elevated threefold by 3 h and remained
      elevated through 9 h. Downregulation of PKC with a second TPA treatment 15 h
      after the first resulted in diminished induction of PGHS-2 expression. Of the
      other promoters examined, anthralin (5 microM), benzoyl peroxide (10 microM), and
      okadaic acid (1 microM) induced PGHS-2 mRNA with different kinetics and to
      different extents. Additionally, the non-tumor-promoting phorbol ester analogue 4
      alpha-12-O-tetradecanoylphorbol-13-acetate induced PGHS-2 mRNA significantly by 1
      h, and this response remained elevated up to 6 h after treatment. Elevated PGHS-2
      expression was also observed by 3 h in response to EGF (10 ng/mL) treatment.
      Collectively, these observations indicate that there are several different
      signaling pathways by which PGHS-2 can be upregulated in murine keratinocytes.

PMID- 8989915
TI  - Ki-ras and p53 mutations are early and late events, respectively, in urethane
      induced pulmonary carcinogenesis in A/J mice.
AB  - In the A/J strain of mice, urethane (ethyl carbamate) induces lung hyperplasia,
      adenoma, and adenocarcinoma in a time-dependent manner. These distinct
      morphological stages may correlate with sequential molecular genetic changes in
      this mouse model. To test this hypothesis, we investigated the presence of
      mutations involving Ki-ras and p53 in urethane-induced lung lesions in A/J mice
      at early and late stages of tumorigenesis. We precisely microdissected 40 lung
      lesions from paraffin-embedded sections. Ki-ras mutations around codon 61 and p53
      mutations in exons 5-8 were identified by polymerase chain reaction-single-strand
      conformation polymorphism and DNA sequencing techniques. In 29 early-stage lung
      lesions classified as hyperplasias (seven) or adenomas (22), we observed 19 Ki
      ras mutations (66%), including three silent mutations and one double mutation at
      different codons, and one silent p53 mutation (3.5%). In 11 late-stage adenomas,
      we identified nine activating Ki-ras mutations (82%) and four missense p53
      mutations (36%). These results indicate that Ki-ras mutations arise early,
      whereas p53 mutations occur relatively late during the benign stages of urethane
      induced lung carcinogenesis in A/J mice.

PMID- 8989916
TI  - Induction of HSP70 gene expression by modulation of Ca(+2) ion and cellular p53
      protein by curcumin in colorectal carcinoma cells.
AB  - Curcumin (diferuloyl methane) is the major active yellow pigment of turmeric and
      curry. Studies in recent years have indicated that curcumin is a potent inhibitor
      of the initiation and promotion of chemical carcinogen-induced skin
      carcinogenesis in mice. When COLO205 colorectal carcinoma cells were treated with
      curcumin (60 microM), the appearance of apoptotic DNA ladders was delayed about 5
      h, and G1 arrest was detected. Further analysis of the endonuclease activities in
      these cells revealed that the activity of Ca(+2)-dependent endonuclease in
      COLO205 cells was profoundly inhibited and that the extent of inhibition depended
      on the degree of calcium depletion. The reduction of p53 gene expression was
      accompanied by the induction of HSP70 gene expression in the curcumin-treated
      cells. These findings suggest that curcumin may induce the expression of the
      HSP70 gene through the initial depletion of intracellular Ca(+2), followed by the
      suppression of p53 gene function in the target cells.

PMID- 8989917
TI  - Inhibition of protein kinase C and proto-oncogene expression by crocetin in
      NIH/3T3 cells.
AB  - Crocetin, a carotenoid isolated from the seeds of Gardenia jasminoides, was found
      to be a potent inhibitor of tumor promotion induced by 12-O-tetradecanoylphorbol
      13-acetate (TPA) in mouse skin. When mouse fibroblast NIH/3T3 cells were treated
      with TPA alone, protein kinase C (PKC) translocated from the cytosolic fraction
      to the particulate fraction. Pretreatment with 60 and 120 microM crocetin for 15
      min inhibited the TPA-induced PKC activity in the particulate fraction by 50% and
      66%, respectively, but did not affect the level of PKC protein. Crocetin also
      reduced the level of TPA-stimulated phosphorylation of cellular proteins. Cells
      pretreated with crocetin (120 microM) had 55% less PKC [3H]phorbol dibutyrate
      binding capacity. Suppression of TPA (100 ng/mL)-induced c-jun and c-fos gene
      expression was also observed in the mouse fibroblast cells pretreated with
      crocetin (30, 60, and 120 microM). Our results provided a basis for understanding
      the inhibitory effect of crocetin on TPA-mediated tumor promotion.

PMID- 8989918
TI  - Specificity of cDNA-expressed human and rodent cytochrome P450s in the oxidative
      metabolism of the potent carcinogen 7,12-dimethylbenz[a]anthracene.
AB  - 7,12-Dimethylbenz[a]anthracene (DMBA), a potent carcinogen, requires metabolic
      activation by cytochrome P450s (P450s) to electrophilic metabolites that result
      in DNA modification, mutagenicity, and carcinogenicity. In this study, we used
      eight human forms, four rodent forms, and one rabbit form of P450 expressed from
      recombinant vaccinia or baculovirus vectors to define their specificity for
      metabolizing DMBA. Of the eight human P450s, 1A1 was the most active (specific
      activity = 14.7 nmol/min/nmol of P450) in total metabolism of DMBA and showed
      approximately 6- to 33-fold more activity than other P450s, 2B6, 2C9, and 1A2
      were also capable of metabolizing DMBA (2.0-2.5 nmol/min/nmol of P450), whereas
      2C8, 2E1, 3A4, and 3A5 exhibited relatively low activities. Among animal P450s,
      mouse 1A1 exhibited activity similar to that of human 1A1 and had 5.0- to 37-fold
      more activity than other rodent and rabbit P450s. In regard to enzyme
      regioselectivity, most human and rodent P450s predominantly formed the 8,9-diol,
      but human 2B6 and rat 2B1 preferentially formed the 5,6-diol. In the production
      of monohydroxymethyl metabolites, all the enzymes yielded more 7-hydroxymethyl-12
      methylbenz[a]anthracene (7HOM12MBA) than 12-hydroxymethyl-7
      methylbenz[a]anthracene (7M12HOMBA), except for human 1A1, which presented the
      reverse selectivity. Human liver microsomes from 10 organ donors were shown to
      metabolize DMBA and in most circumstances generated the metabolic profile DMBA
      trans-8,9-dihydrodiol > 7HOM12MBA > or = DMBA trans-5,6-dihydrodiol > or = 7,12
      dihydroxymethylbenz[a]anthracene > 7M12HOMBA > DMBA trans-3,4-dihydrodiol. Thus,
      the combined activity of hepatic microsomal 2C9, 1A2, and 2B6 may contribute to
      the metabolic activation and the metabolism of DMBA in normal human liver.

PMID- 8989919
TI  - Metastatic behavior of prostatic tumor as influenced by the hematopoietic and
      hematogenous factors.
AB  - Metastasis represents a hallmark of the tumor cell's escape from normal cellular
      behavior to acquired invasive and migratory style. Metastasis of prostate cancer
      (Pca) depends upon the interplay of a series of hematogenous and hematopoietic
      factors. We investigated the role of some of those factors implicated in the
      dissemination process in two separate sublines of adenocarcinoma of the prostate.
      Our data revealed that (1) the urokinase plasminogen activator activity was
      significantly higher in R3327-AT3, an aggressive metastatic tumor, as compared to
      R3327-G, a nonmetastatic tumor of the prostate, (2) the concentration of
      platelets decreased, and the platelet-aggregating activity increased
      significantly when the platelets were reacted with exogenous aggregating agents
      and tumor effusions to suggest that activation of the hemostatic system could
      protect tumor cells from immunosurveillance and facilitate the process of
      hematogenous dissemination, and (3) transferrin, which has been reported to have
      a growth-promoting effect on Pca, did not show any appreciable effect on tumor
      growth but did alter the level of in vitro adherence which possibly could lead to
      better attachment and increased invasive behavior of tumor cells.

PMID- 8989920
TI  - Expression of sex hormone-binding globulin mRNA in uterine cervical cancers.
AB  - To explore the role of sex hormone-binding globulin (SHBG) in the intracellular
      steroidal actions in human uterine cervical cancers, the expression of SHBG mRNA
      as a manifestation of intracellular SHBG expression was investigated using the
      competitive reverse transcription-polymerase chain reaction-Southern blot
      analysis. The expression of SHBG mRNA was detected in all cervical endometria and
      cancers analyzed. The levels of SHBG mRNA in cervical cancers were significantly
      lower (p < 0.01) than in the normal cervical endometrium. In cervical cancers,
      the levels of SHBG mRNA in cervical adenocarcinomas were significantly higher (p
      < 0.01) than in keratinizing and small cell nonkeratinizing squamous cell
      carcinomas, and tended to be higher than in large cell nonkeratinizing squamous
      cell carcinomas. There was no difference in expression among the clinical stages
      of cervical cancers. These data suggest that human uterine cervical cancers,
      especially adenocarcinomas, might synthesize SHBG intracellularly, and might
      conserve the activity of SHBG-related steroidal mechanisms to some extent.

PMID- 8989921
TI  - Comparative study on expression of plasminogen activator inhibitor 1 and its mRNA
      in endometrial cancers and normal endometria.
AB  - The effects of the endocrine milieu on growth, invasion and metastasis,
      associated with neovascularization of endometrial cancer, the expression of
      plasminogen activator inhibitor 1 (PAI-1), and its mRNA in endometrial atypical
      hyperplasia and cancer, and normal endometria as controls were determined in
      premenopausal and postmenopausal women. In premenopausal women, the levels of PAI
      1 and its mRNA in normal endometria were significantly higher than in endometrial
      atypical hyperplasia and cancer. On the other hand, in postmenopausal women, the
      results were reversed. There was no difference in the expression of PAI-1 and its
      mRNA in the various histological grades and clinical stages in endometrial
      cancers, while the expression of PAI-1 in other cancers increased during tumor
      progression. In our previous study, the expression of PAI-1 and its mRNA in well
      differentiated endometrial cancer cell lines was dependent upon estrogen and
      progesterone. This might be partially related to the endocrine milieu, especially
      in endometrial atypical hyperplasia and well-differentiated endometrial cancer,
      which seems to be dependent on sex steroids. Therefore, endometrial cancer of any
      histological grade and clinical stage might maintain PAI-1 expression in both
      premenopausal and postmenopausal women, which may modulate, at least in part,
      growth, invasion and metastasis associated with neovascularization of endometrial
      cancer.

PMID- 8989922
TI  - Combined effect of tamoxifen or interferon-beta and 4-hydroxyphenylretinamide on
      the growth of breast cancer cell lines.
AB  - To improve the effectiveness of 4-hydroxyphenylretinamide (4-HPR), an analogue of
      retinoic acid used in chemoprevention and treatment of breast cancer, we
      investigated the effect of concomitant administration of 4-HPR (0.1, 1 microM)
      and tamoxifen (TAM, 0.1, 1 microM), or 4-HPR and interferon-beta (IFN-beta, 10,
      100, 500 IU/ml) on the growth of four cell lines (MCF7, T47D, MDA-MB231 and BT20)
      characterized by a different steroid receptor profile. A high concentration of 4
      HPR caused a significant inhibitory effect not only on the estrogen receptor
      positive cell lines (MCF7 and T47D), but also on one (BT20) of the two estrogen
      receptor-negative cell lines. IFN-beta displayed a dose-dependent inhibitory
      effect in all cell lines, but it was most evident in MCF7 cells. In all cell
      lines, the combination of 4-HPR (0.1 microM) and TAM (1 microM) or IFN-beta (500
      IU/ml) generally caused additive or synergistic effects. In particular, the
      finding that in estrogen receptor-negative MDA-MB231 cells 4-HPR (which at 1
      microM was singly ineffective) in combination with TAM at 1 microM or any
      concentration of IFN-beta produced a synergistic effect suggests that the
      compound could act through a pathway independent of specific receptors for
      retinoids. Our results indicate that intrinsic characteristics of cells can
      influence responsiveness to 4-HPR, TAM and IFN-beta, singly or in association,
      ever within cell lines with similar steroid receptor profiles. Thus, more
      attention should be payed to the biological characteristics of the single tumor
      in order to help choose the best combination of drugs to be applied.

PMID- 8989923
TI  - Alpha-fetoprotein as a TNF resistance factor for the human hepatocarcinoma cell
      line HepG2.
AB  - Human hepatocarcinoma HepG2 cells are known to be insensitive to tumor necrosis
      factor (TNF) cytotoxicity. In this report, preliminary washing of HepG2 cells
      with serum-free medium to remove endogenous and exogenous alpha-fetoprotein (AFP)
      from the cultivation medium transfers cells from the TNF-resistant to the TNF
      sensitive state without addition of any transcriptional inhibitors. HepG2 cells
      sensitized to by washing again became TNF-resistant after their treatment with
      exogenous AFP. Protective AFP activity against TNF-induced cytotoxicity directly
      depends on the AFP/TNF concentration ratio, demonstrating biphasic AFP activity.
      Our data show that 0.2 mg/ml of AFP acts synergistically to enhance cytotoxicity
      of suboptimal TNF doses. In contrast, the same AFP dose significantly attenuates
      the cytotoxicity of high TNF doses. It is concluded that AFP can function as a
      protective factor against TNF cytotoxicity in human hepatoma cells. These
      observations suggest that AFP secretion by certain tumor cells allows a highly
      flexible regulation of TNF cytotoxicity, dependent on the amount of endogenous
      AFP.

PMID- 8989924
TI  - Effects of in vivo culture of murine mammary adenocarcinoma cells on tumor and
      metastatic growth.
AB  - We studied the effect of tumoral microenvironments on metastatic phenotypes.
      Therefore, murine mammary adenocarcinoma cells cultured in vivo in diffusion
      chambers (DC) were implanted intraperitoneally in BALB/c mice. The behavior of DC
      cultured cells was compared with that of cells obtained from tumors growing
      subcutaneously or intraperitoneally and from primary cultures in vitro of the
      former. DC-cultured and control cells were inoculated into normal mice to
      evaluate their tumorigenicity and metastasizing ability. We found that DC
      cultured cells were less tumorigenic and metastatic both in spontaneous and in
      experimental metastasis assays. The host response to tumor progression resulted
      in an early leukocytosis, probably due to the overproduction of a hematopoietic
      factor by the tumor cells. Finally, it was found that DC-cultured cells produced
      lower levels of urokinase-type plasminogen activator activity, while no
      differences were found in the metalloproteinase production compared to cells
      obtained from a tumor growing subcutaneously.

PMID- 8989925
TI  - Detection of thymidylate synthase gene expression levels in formalin-fixed
      paraffin embedded tissue by semiquantitative, nonradioactive reverse
      transcriptase polymerase chain reaction.
AB  - We describe a new, simple and reliable semiautomated strategy for quantifying
      mRNA from archival specimens by using oligo(dT)25 paramagnetic beads and the
      reverse-transcriptase polymerase chain reaction (PCR) coupled with quantitative
      digital image analysis (Q-DIA). To evaluate the experimental conditions, we
      examined thymidylate synthase (TS) gene expression in mRNA isolated from both
      flash-frozen and formalin-fixed paraffin-embedded human biopsy samples using
      biopsy material obtained from 2 patients prior to chemotherapy with 5
      fluorouracil. Following the electrophoretic separation of the PCR products
      through a 20% polyacrylamide gel, quantitation of the perimeters of the silver
      nitrate-stained PCR products will be done by Q-DIA using a video frame-grabber
      board attached to a CCD camera using Image-Pro+ software. Validation of this
      approach will involve a comparison of the observed gene expression levels to TS
      protein levels obtained by tissue homogenization assays of TS, tetrahydrofolate,
      5,10-methylenetetrahydrofolate, 2'-deoxyuridine-5'-monophosphate and 5-fluoro-2'
      deoxyuridylate (FdUMP), by established [3H]FdUMP ligand-binding assays. The
      novelty of this method is that it offers a low-cost means whereby Q-DIA is
      performed directly from the gel to rapidly and accurately determine the level of
      TS gene expression, which is standardized against the beta-actin housekeeping
      gene. In the protocol described herein, gene expression studies can be done
      quickly and without the use of radioactive substances in both normal clinical
      samples shock frozen at the time of surgical excision and in formalin-fixed
      paraffin-embedded archival samples, which are commonly available in all hospital
      pathology departments. To demonstrate the utility of this method, mRNA was
      extracted from both nonpathological and tumor biopsies originating from both
      types of material from the same patients. TS gene expression in the flash-frozen
      and archival materials was compared to the level of TS intracellular enzyme
      activity in the same samples and a correlation of 89 and 80% between the shock
      frozen and archival material relative to TS intracellular enzyme activity levels
      was observed. These findings suggest that routine semiautomated quantitative
      analysis of rare mRNA transcripts, e.g. TS, from archival material can be applied
      for retrospective studies.

PMID- 8989926
TI  - Melanoma in situ versus melanocytic hyperplasia in sun-damaged skin. Assessment
      of the significance of histopathologic criteria for differential diagnosis.
AB  - For differentiation of melanoma in situ (MIS) from melanocytic hyperplasia (MH)
      in sun-damaged skin, several criteria have been proposed. To assess sensitivity
      and specificity of those criteria, we examined the epidermis adjacent to 50
      consecutive basal cell carcinomas and 50 MISs in skin with significant solar
      elastosis. The most valuable criteria for the diagnosis of MIS, as opposed to MH,
      were presence of nests of melanocytes, irregular distribution of melanocytes,
      descent of melanocytes far down adnexal epithelial structures, irregular
      distribution of pigment, presence of melanocytes above the junction, a high
      number of melanocytes, pleomorphism of melanocytes, and atypical nuclei of
      melanocytes. Other criteria, e.g., collapse of cytoplasm around nuclei of
      melanocytes; flattening of rete ridges; differences in the area, shape, and
      contour of nuclei of melanocytes as assessed by nuclear morphometry; and presence
      of melanocytes stained by HMB-45 and Ki-67/MIB-1 monoclonal antibodies, were
      found to be of low or no value for differential diagnosis.

PMID- 8989927
TI  - Measurement of the maturation parameter by using computer-assisted interactive
      image analysis may be helpful in the differential diagnosis between compound
      Spitz nevus and malignant melanoma.
AB  - The so-called maturation parameter (MP) (that is, the ratio of the mean nuclear
      areas in the deep portion and in the superficial portion of a tumor) was measured
      and calculated using a computer-assisted interactive image analysis system in 29
      compound Spitz nevi (SNs) and 37 primary invasive cutaneous malignant melanomas
      (MMs), of which 16 and 14 lesions, respectively, measured up to 1 mm in Breslow
      thickness (that is, thin). The MPs of the SNs and MMs were found to be 0.37-0.89
      (mean +/- SD, 0.64 +/- 0.1) and 0.81-1.16 (mean +/- SD, 0.96 +/- 0.1),
      respectively (p < 0.001). The MPs of the subgroups of thin SNs and MMs were 0.56
      0.87 (mean +/- SD, 0.67 +/- 0.1) and 0.86-1.10 (mean +/- SD, 0.98 +/- 0.1),
      respectively (p < 0.001). Most of the SNs and MMs had MP values of < 0.81 and >
      0.89, respectively. This pattern of distribution prevailed in the subgroup of
      thin lesions. Thus, the previously shown difference in MPs between SN and MM for
      thicker lesions (> or = 1.0 mm) was demonstrated in this study in thin lesions (<
      or = 1.0 mm) as well. Although a relatively small area of overlap in MP values
      exists between compound SNs and MMs, including the thin ones, below this area the
      lower the MP value the more likely the diagnosis is SN, and vice versa.

PMID- 8989928
TI  - Heterogeneity of Borrelia burgdorferi in the skin.
AB  - The reliability of various in vitro techniques to identify Borrelia burgdorferi
      infection is still unsatisfactory. Using a high-power resolution videomicroscope
      and staining with the borrelia genus-specific monoclonal flagellar antibody
      H9724, we identified borrelial structures in skin biopsies of erythema chronicum
      migrans (from which borrelia later was cultured), of acrodermatitis chronica
      atrophicans, and of morphea. In addition to typical borreliae, we noted stained
      structures of varying shapes identical to borreliae found in a "borrelia-injected
      skin" model; identical to agar-embedded borreliae; and identical to cultured
      borreliae following exposure to hyperimmune sera and/or antibiotics. We conclude
      that the H9724-reactive structures represent various forms of B. burgdorferi
      rather than staining artifacts. These "atypical" forms of B. burgdorferi may
      represent in vivo morphologic variants of this bacterium.

PMID- 8989929
TI  - Cell proliferation and p53 protein expressions in cutaneous epithelial neoplasms.
AB  - We investigated correlations between cell proliferation, p53 overexpression, and
      degree of malignancy in cutaneous epithelial neoplasms. One hundred and fourteen
      cases of epithelial neoplasms, including seborrheic keratosis (SEB), basal cell
      carcinomas (BCCs), solar keratosis (SK), Bowen's disease (BD), and squamous cell
      carcinomas (SCCs) were examined using argyrophilic nucleolar organizer region
      (AgNOR) staining. In addition, immunohistochemical analysis using the Ki-67 (MIB
      1) and anti-p53 (DO-7) monoclonal antibodies was performed. The ratio of tumorous
      to normal cells according to AgNOR staining was defined as the AgNOR rate, and
      the ratio of tumorous to normal cells according to Ki-67 recognition was defined
      as the Ki-67 rate. SCC lesions showed the highest AgNOR rate among the
      investigated epithelial neoplasms, followed in order by BD, BCC, SK, and SEB
      lesions. The Ki-67 rate was highest in BD lesions, followed in order by SK, SCC,
      BCC, and SEB lesions. Expression of p53 protein was highest in SK lesions. SCC is
      generally considered to be the most malignant neoplasm, followed in order by BCC,
      BD, and SK. Thus, our results suggest that the Ki-67 rate and overexpression of
      p53 protein do not always reflect the degree of malignancy in neoplasms.

PMID- 8989930
TI  - Demodex-associated folliculitis.
AB  - Examination of 388 follicles in 24 large resections of skin for the presence of
      histologic folliculitis and Demodex mites uncovered a nonrandom association
      between these two phenomena. Demodex mites were found in 42% of follicles with
      inflammation, but in just 10% of the follicles without inflammation. Eighty-three
      percent of follicles with Demodex showed inflammation. The probability that this
      result could occur by random chance alone was < 0.001, thus suggesting that
      Demodex is associated with histologic folliculitis, even minor folliculitis. The
      results do not, however, decide whether Demodex is causative, whether it
      preferentially selects follicles with histologic inflammation, or whether some of
      both processes operate.

PMID- 8989931
TI  - Phenotypic heterogeneity of nodular hidradenoma. Immunohistochemical analysis
      with emphasis on cytokeratin expression.
AB  - We studied the immunohistochemical phenotype in 13 cases of the nodular
      hidradenoma (NH), with special emphasis on the expression of different types of
      keratins (cytokeratins, 7, 10, 6/18, 8/18, and 10/17/18 and their distribution in
      normal sweat glands. Variable reactions with keratins, alpha-smooth muscle actin,
      and epithelial membrane antigen (EMA) were found, as these markers were present
      in different cellular components of the tumors. The most constant finding was
      almost complete absence of cytokeratins (all but keratin 10/17/18, which was
      positive in two of 13 cases) in clear cells, which yet were positive for EMA. The
      tumors expressed mostly cytokeratin 6/18, 7, 8/18, and 10/17/18, which were found
      in 11, 13, 11, and 12 cases, respectively. The cellular distribution and quantity
      of stained cells differed, as keratins 6/18, 8/18, and 7 produced the most
      abundant staining and were predominantly localized in small squamoid cells and
      the cells lining the tubular and cystic spaces. Cytokeratin 10/17/18 was
      expressed in smaller or larger clusters of squamoid cells and rarely in clear
      cells. Cytokeratins 10, 19, and 20 were found sporadically in single cells or
      small cellular clusters. alpha-Smooth muscle actin was expressed in four cases,
      whereas we did not find reactivity of S-100 protein. Comparing these results with
      the pattern of keratin distribution and antigenic reactivity in eccrine sweat
      glands, we conclude that NH presents cellular heterogeneity of its elements and
      differentiation toward different parts of the sweat gland.

PMID- 8989932
TI  - Bacillary angiomatosis in an immunocompetent child.
AB  - Bacillary angiomatosis (BA) is a pathological process characterized by prominent
      vascular proliferation secondary to organisms of the genus Rochalimaea. BA has
      been most commonly associated with HIV-1+ patients, but has also been reported
      rarely in other immune-suppressed patients and in a small group of patients with
      no demonstrated immune suppression. Even in immune-suppressed children, BA is
      extremely rare. We report a 5-year-old girl with no apparent immune suppression
      and no risk factors for HIV-1+ disease, who presented with a skin lesion that
      histopathologically was diagnostic of BA.

PMID- 8989933
TI  - Primary cutaneous Ewing's family sarcoma. Report of a case with immunostaining
      for glycoprotein p30/32 mic2.
AB  - The differential diagnosis of cutaneous small round cell malignancies is a
      relatively uncommon but recurrent problem that usually requires adjuvant
      techniques including special histochemical stains, immunohistochemistry (IHC),
      electron microscopy (EM), and cytogenetics (CG) to arrive at a definite answer.
      This report describes a case of a primary cutaneous malignancy that, after
      workup, fulfilled the criteria of extraskeletal Ewing's family sarcoma, which was
      corroborated by IHC with an antibody to glycoprotein p30/32 mic2 that is highly
      expressed in these neoplasms. The lesions consisted of a large nodular
      proliferation of poorly differentiated monotonous small round cells confined to
      the dermis and subcutaneous tissue. The cells had high nuclear to cytoplasmic
      (N/C) ratios, scattered prominent nucleoli, and indistinct cytoplasm. A periodic
      acid-Schiff (PAS) stain with and without diastase demonstrated abundant
      cytoplasmic glycogen. The glycogen was confirmed with EM, which did not show
      neurosecretory granules, but extensive sectioning of the tissue blocks
      demonstrated with light microscopy a single focus with pseudorosette formation.
      IHC was positive for monoclonal antibody (MAb) O13 to glycoprotein p30/32 mic2
      and negative for lymphoid (CD45), neural (S-100, NF, GFAP), neuroendocrine (NSE),
      and muscle (MSA, desmin) markers. To the best of our knowledge, this is one of
      few reported cases of primary cutaneous (extraskeletal/extraosseous) Ewing's
      sarcoma (EEWS) and the first to use IHC with MAb O13, which recognizes the cell
      surface glycoprotein p30/32 mic2. This case further illustrates the continuum
      between EEWS and primitive peripheral neuroepithelioma and supports the unifying
      concept that these two entities are merely subtle morphologic variants of the
      same malignant neoplasm, which is better designated a Ewing's family sarcoma.

PMID- 8989934
TI  - Multiple retiform hemangioendotheliomas. A low-grade angiosarcoma.
AB  - We present the case of a 30-year-old woman who over a 10-year period has
      developed multiple well-differentiated angiosarcomas involving the trunk and
      extremities. The clinical and histologic features are characteristic of retiform
      hemangioendothelioma (RH), a distinctive form of low-grade angiosarcoma. This
      case is unique in that multiple lesions developed in different anatomic sites. We
      discuss the clinical and histologic characteristics, diagnosis, and prognosis of
      RH.

PMID- 8989935
TI  - Onychomycosis and keratomycosis caused by Alternaria sp. A bipolar opportunistic
      infection in a wood-pulp worker on chronic steroid therapy.
AB  - We report a case of Alternaria infection of the nail and cornea in an
      immunocompromised patient working in the paper-manufacturing industry. This
      unusual clinical presentation could represent an occupational disorder. The
      importance of histologic examination of the altered nails is emphasized. The
      proof of a real nondermatophytic onychomycosis is established only when hyphae of
      culture-proven molds are shown inside the nail plate.

PMID- 8989936
TI  - Carcinosarcoma of the skin. Case report and literature review.
AB  - A case of carcinosarcoma arising in the skin of the left arm of a 69-year-old
      woman is reported with a review of the literature. The tumor was composed of low
      differentiated squamous cell carcinoma, which was intermingled with a pleomorphic
      sarcoma. The carcinomatous component had keratin and lacked vimentin, whereas the
      phenotype of the sarcomatous portion was the reverse. The former presented
      additionally focal expression of S-100 protein, which was lacking in other
      portions of the carcinoma. The phenotypic data, supplemented by p53
      immunostaining, which was present in both components, suggest their common origin
      in this tumor.

PMID- 8989937
TI  - Solitary sclerotic fibroma of the skin: a sclerotic dermatofibroma?
AB  - Two cases of solitary tumors showing well-demarcated hypocellular, dermal
      fibrocollagenous proliferations are reported. The lesions were composed of
      hyalinized eosinophilic collagen bundles arranged in the characteristic
      interwoven pattern with prominent clefts, as described in sclerotic fibroma of
      the skin. This pattern, although predominant, was not uniform. Some areas showed
      a more cellular pattern with histopathologic features suggestive of
      dermatofibroma. In those areas, multiple spindle-shaped cells and occasional
      multinucleated cells were observed. The collagen bundles did not adopt a whorled
      pattern, and the overlying epidermis showed mild acanthosis and elongation of the
      rete ridges. The sclerotic changes were present mainly at the periphery and in
      the deep areas of the tumor. Our observations confirm the possibility that
      solitary sclerotic fibroma of the skin may represent, at least in some instances,
      the later and sclerotic stage of other more cellular neoplasms (specifically
      dermatofibromas) rather than an individualized neoplasm, as has been recently
      proposed.

PMID- 8989939
TI  - Cutaneous metastasis of an osteosarcoma. A case report.
AB  - Sarcomas seldom metastasize to the skin. This report describes a rare instance of
      this phenomenon. A 24-year-old patient with a history of osteosarcoma
      (osteoblastic type) of the right humerus was seen with a cutaneous nodule on the
      left temple. Histologic examination of the skin showed the lesion to be a
      metastatic osteosarcoma. On histologic examination, a proliferation of bizarre
      mononucleated or multinucleated osteoblastic cells was noted in the dermis and
      subcutis. Although osteoid formation and calcification were not recognized, as
      they had been in contrast to the primary lesion, basic structures and components
      of the skin lesion were identical to those of the primary tumor tissue. Cutaneous
      metastasis from on osteosarcoma of bone is an extraordinarily rare event and, as
      far as we can determine, has only been reported three times.

PMID- 8989938
TI  - Primary neuroendocrine carcinoma of the skin with an unusual follicular
      lymphocytic infiltrate of the dermis.
AB  - Primary neuroendocrine carcinoma of the skin (PNECS) is a rare cutaneous tumor
      occurring predominantly on sun-exposed skin of elderly people. This
      histomorphological appearance of this aggressive tumor can be highly variable
      depending on the predominating growth pattern. We present an unusual case of
      PNECS: the tumor masked by a dense lymphoid infiltrate with a well-formed
      follicular growth pattern. In these cases of PNECS, the differential diagnosis
      must be extended to lymphoid neoplasms as well as lymphoepithelial neoplasms.

PMID- 8989940
TI  - Metastatic testicular choriocarcinoma of the skin. Report and review of the
      literature.
AB  - Choriocarcinoma is a malignant growth of trophoblastic cells characterized by
      secretion of human chorionic gonadotropin. Choriocarcinoma usually arises from
      fetal trophoblasts and rarely arises from germ cells in the testis or ovary or
      derives from dedifferentiation of other carcinomas. Skin metastasis of
      choriocarcinoma is rare: only seven cases have been reported in the English and
      Japanese literature. We report the case of a 22-year-old Japanese man with pure
      choriocarcinoma of the testis who developed skin metastases that presented as
      multiple reddish nodules. Microscopic examination of both the primary lesion of
      the testis and the cutaneous metastasis demonstrated the typical histologic
      features of pure choriocarcinoma. The patient died 3 months after the initial
      onset of skin metastasis. Review of the literature indicates that skin metastasis
      of choriocarcinoma usually occurs as a nodular lesion with the histologically
      typical feature of the primary disease and signals of poor prognosis.

PMID- 8989941
TI  - Lymphoepithelioma-like carcinoma of the skin.
AB  - The histopathological findings of two cases of primary lymphoepithelioma-like
      carcinoma (LELC) of the skin occurring in two elderly Chinese individuals are
      presented. Microscopically, they were well circumscribed and were composed of
      irregular nests of malignant epithelial cells in a background of reactive
      lymphoid cells including mature plasma cells. A focus of epithelial dysplasia was
      noted in the adjacent epidermis in one case, suggesting that the LELC might have
      originated from the overlying epidermis. The epithelial nature of the tumors was
      confirmed by cytokeratin staining. In situ hybridization for Epstein-Barr virus
      encoded RNA (EBER) showed that the tumor cells were uniformly negative, although
      positive signals were detected in scattered background lymphocytes in case 1. Our
      results confirm the previous observation that LELC of skin is not related to
      Epstein-Barr virus, even in Chinese subjects. Nevertheless, such negative
      findings may prove to be of diagnostic value in excluding the alternative more
      common diagnosis of metastatic nasopharyngeal carcinoma, which is uniformly
      positive for EBER.

PMID- 8989942
TI  - Hybrid cysts showing alternate combination of eruptive vellus hair cyst,
      steatocystoma multiplex, and epidermoid cyst, and an association among the three
      conditions.
AB  - Eruptive vellus hair cyst (EVHC), steatocystoma multiplex (SM), and epidermoid
      cyst are characterized by formation of multiple cutaneous cysts and have a
      resemblance in clinical features but have distinctive histologic features. We
      present herein two patients, who had EVHC, SM, and EVHC with sebaceous gland, and
      who also had EVHC, SM, and epidermoid cyst with sebaceous gland and vellus hairs.
      In addition, the interrelation among the three diseases is discussed. We think
      that EVHC, SM and epidermoid cyst are within the same spectrum of the disease
      process.

PMID- 8989943
TI  - Enduring myths.

PMID- 8989944
TI  - Neurotologic skull base surgery.

PMID- 8989945
TI  - Predictive value of intraoperative brainstem auditory evoked responses in surgery
      for conductive hearing losses.
AB  - OBJECTIVE: To assess the efficacy of intraoperative brainstem auditory evoked
      responses (BAER) in predicting postoperative hearing improvement in surgery for
      conductive hearing loss. STUDY DESIGN: A prospective study of consecutive
      patients undergoing surgery for conductive hearing loss under general anesthesia
      by a single surgeon. SETTING: A tertiary care university affiliated medical
      center. PATIENTS: All patients undergoing surgery for conductive hearing loss by
      the senior author between June 25, 1993 and March 20, 1995. INTERVENTIONS: Pre-
      and postreconstruction intraoperative BAERs; pre- and postoperative pure tone and
      speech audiometry. MAIN OUTCOME MEASURES: Changes in audiometric pure tone air
      conduction thresholds, bone-air gaps (BAG), and speech reception thresholds
      (SRT), compared with changes in BAER wave five (V) latencies. RESULTS: A decrease
      in the wave V latency on the intraoperative BAER correlates significantly with
      improvement in postoperative pure-tone air-conduction, BAG, and SRT using chi 2
      and linear regression analyses. CONCLUSIONS: Improvement in intraoperative BAER
      correlates with postoperative hearing improvement in surgery for conductive
      hearing loss done under general anesthesia in our population.

PMID- 8989946
TI  - Refined mastoid reconstruction with the pedicled postauricular perichondrial
      flap.
AB  - Successful canal wall reconstruction after open cavity surgery may be compromised
      by both immediate (graft dehiscence and infection) or delayed (graft retraction,
      absorption, and extrusion) complications. Many of the healing problems following
      canal wall reconstruction are related to incomplete soft tissue coverage of the
      graft and limited blood supply. Under these conditions, we sought to increase
      graft viability with a broad-based perichondrial flap developed from the
      posterior surface of the auricle. The flap was used over a period of 3 years at a
      tertiary referral center in 36 cases of canal wall reconstruction in conjunction
      with composite grafts of cartilage and perichondrium. The patients ranged in age
      from 12 to 63 years and in all cases had undergone a canal down
      tympanomastoidectomy that was reconstructed either primarily or secondarily. The
      canal wall was successfully reconstructed in 35 of 36 ears. These results
      demonstrate a reduction in our dehiscence rate from 10 to 3% since the
      introduction of the perichondrial flap. With the perichondrial flap, we were
      consistently able to achieve better soft tissue coverage of the composite
      cartilage graft, eliminate lateral graft dehiscence, and encourage
      reepithelization of the canal. By implication, we believe this flap provides a
      source of nutritional support for the free cartilage graft as well as the
      overlying skin.

PMID- 8989947
TI  - Histopathology of labyrinthine fistulae in chronic otitis media with clinical
      implications.
AB  - The objective of this study was to describe the light microscopic pathology of
      labyrinthine fistulae in chronic otitis media (COM) in seven temporal bones and
      to discuss clinical and surgical implications. In COM, labyrinthine fistulae are
      usually caused by cholesteatoma, with the lateral semicircular canal being the
      most commonly affected site. Some fistulae are asymptomatic, whereas, others
      affect the auditory and vestibular systems to varying degrees. Surgical removal
      of cholesteatoma matrix over a fistula carries a risk of sensorineural hearing
      loss. Knowledge of the pathology of fistulae may provide a better understanding
      of their clinical manifestations and may allow a more rational approach to
      surgical management. The Massachusetts Eye and Ear Infirmary temporal bone
      collection contains 115 specimens with COM, of which seven specimens show
      pathologic fistulization of the bony labyrinth. Histologic sections from these
      seven bones were evaluated with respect to type of COM, location and size of
      fistula, changes in the inner ear adjacent to the fistula, middle ear and mastoid
      disease, and pathology in the vestibular and cochlear sense organs. The following
      conclusions are presented (a) Labyrinthine fistulae can be caused not only by
      cholesteatoma, but also by granulomatous COM without cholesteatoma and even by
      localized infection within a canal-down mastoid cavity. (b) Cholesteatoma matrix
      or inflammatory tissue usually becomes apposed to the endosteum or membranous
      labyrinth within the fistula. In most cases, reactive inner ear changes do not
      occur at the fistula site. Occasionally, there is thickening of the endosteum or
      chronic localized labyrinthitis. (c) Most bones do not show any alterations of
      the vestibular and cochlear sense organs. Occasionally, there is serous
      labyrinthitis, which might lead to partial sensorineural hearing loss. (d) A
      protective "walling-off" phenomenon in the labyrinth is not common. Therefore, if
      overwhelming infection or surgical trauma breaches the natural barriers of the
      endosteum/membranous labyrinth, then the fistula may allow rapid dissemination of
      infection throughout the inner ear.

PMID- 8989949
TI  - Arterial dissection of the vertebrobasilar systems: a possible cause of acute
      sensorineural hearing loss.
AB  - OBJECTIVE: Our goal was to describe three cases of acute sensorineural hearing
      loss (ASNHL) that might be caused by arterial dissection of the vertebrobasilar
      system. DESIGN: Retrospective case review. SETTING: Yamagata University Hospital,
      Yamagata, Japan. PATIENTS: Thirty-seven patients with ASNHL underwent magnetic
      resonance (MR) imaging between September 1993 and March 1995. INTERVENTIONS:
      Proton density and T2-weighted axial images and three-dimensional spoiled
      gradient-recalled acquisition in steady state (3-D SPGR) imaging with
      gadopentetate dimeglumine were obtained with a 1.5 T MR system in all patients.
      T1-weighted images were obtained in 23 patients. Vertebral angiography (VAG) was
      performed in 4 of the 37 patients. RESULTS: In 3 of the 37 patients, the presence
      of vertebrobasilar dissection was confirmed: contrast-enhanced 3-D SPGR images
      disclosed double lumen of the proximal basilar artery and/or the ipsilateral
      vertebral artery in all of the 3 patients. In two of them, the vertebrobasilar
      dissection was also confirmed by VAG. The hearing loss of all three patients
      improved after the onset. Audiograms revealed no characteristic pattern of the
      initial hearing loss among them. CONCLUSIONS: Vertebrobasilar dissection may
      cause an intramural hematoma involving the orifice of the anterior inferior
      cerebellar artery or a distal thromboembolism reducing the blood flow of the
      labyrinthine artery; these conditions can lead to onset of hearing loss. Arterial
      dissection of the vertebrobasilar system might be one of the causes of ASNHL.

PMID- 8989948
TI  - Vascular loops of the internal auditory canal: a diagnostic dilemma.
AB  - OBJECTIVE: To describe clinical and radiographic characteristics of vascular
      loops occupying the internal auditory canal. STUDY DESIGN AND SETTING: A
      retrospective review of patients with lesions initially suggestive of neoplasm,
      such as acoustic neuroma, who were subsequently found to have vascular
      compression of the facial and/or cochleovestibular nerves. The symptoms
      suggestive of this retrocochlear pathology, including vertigo, tinnitus, hearing
      loss, hemifacial spasm, and facial paralysis, were assessed. Subsequent
      evaluation with MRI revealed findings suggestive of intracannalicular neoplasm in
      three patients. MAIN OUTCOME MEASURES: Vascular loops with the cerebellopontine
      angle have been reported to approach the facial and cochleovestibular nerves at
      the level of the porus acousticus or within the internal auditory canal in
      approximately 65% of postmortem specimens. Although presumably the majority of
      individuals are asymptomatic, several cases are presented where vascular loop
      compression created symptoms and radiographic findings suggestive of neoplasm.
      RESULTS: Within this study, two patients underwent surgical exploration for
      expected neoplasm and were subsequently found to have pathology secondary to
      vascular loop compression. A third patient avoided surgical exploration due to
      radiographic confirmation with angiography. CONCLUSIONS: Although skepticism
      exists regarding true pathology occurring secondary to vascular loop compression,
      histologic confirmation of neural compression injury secondary to a vascular loop
      is presented. Further, diagnostic parameters and treatment are presented as well.

PMID- 8989950
TI  - Comparative psychophysical evaluation in cochlear implantation: electrical and
      magnetic stimulation.
AB  - Transtympanic electrical stimulation, either in the form of round window or
      promontory placement of electrode prior to cochlear implantation is an accepted
      and commonly used psychophysical tool. Certain response parameters have been
      identified as predictors of outcome. This study compared the subjective auditory
      responses generated by promontory electrical stimulation (PES) with those from
      two noninvasive modalities, namely peritympanic electrical stimulation (PTES) and
      transcranial magnetic stimulation (TMS). Ten postlingually deafened adult
      cochlear implant candidates were studied. Standard psychophysical parameters were
      obtained from patients undergoing PES and PTES. A more subjective form of
      evaluation was conducted for TMS. Subsequently, nine patients received the
      multichannel Nucleus (Cochlear Corp., Denver, CO, U.S.A.) implant and one patient
      a Clarion (Advanced Bionics, Sylmar, CA, U.S.A.) implant. Compared with PES. PTES
      elicited increased threshold responses with similar dynamic ranges between 50 and
      400 Hz of stimulation. The differences were, by and large, insignificant. PTES
      appeared to be a useful alternative in selected individuals owing to its
      noninvasiveness. TMS, on the other hand, was incapable of clearly inducing
      auditory percepts. It also produced concomitant facial and trigeminal
      stimulation, limiting its potential use as a prognostic tool.

PMID- 8989952
TI  - Intratympanic gentamicin in Meniere's disease: results of therapy.
AB  - To define better the benefits and risks of intratympanic gentamicin injection
      treatment of intractable vertigo or drop attacks due to Meniere's disease, we
      reviewed the charts of 18 patients whom we have now observed for > 1 year after
      having completed this mode of therapy. There were nine women and nine men aged 29
      81 years; all had poor hearing in the affected ear. Of the 18 patients, 14 have
      had no further vertigo or drop attacks (11 patients after a single set of three
      to five injections, another three after a further set of one to five injections).
      The treatment could be effective even if it did not abolish caloric responses
      from the treated ear, even if it did not produce an acute vestibular
      deafferentation syndrome afterwards, and even after a failed vestibular nerve
      section. After treatment, five of the 18 patients developed oscillopsia and
      ataxia--symptoms and signs of (presumably permanent) chronic vestibular
      insufficiency; this proportion is not obviously lower than that after vestibular
      neurectomy or surgical labyrinthectomy. Of the 18 patients, 12 showed no change
      in the 1-kHz threshold and 13 showed no change in the 4-kHz threshold. When
      hearing did deteriorate, the threshold rose by more than 30 dB at 1 kHz in four
      patients and at 4 kHz in six patients. We conclude and confirm that intratympanic
      gentamicin injections are a convenient and, in most cases, effective and safe
      treatment for intractable vertigo or drop attacks due to Meniere's disease.

PMID- 8989951
TI  - Intratympanic gentamicin therapy for Meniere's disease.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of intratympanic gentamicin
      therapy for the treatment of Meniere's disease. STUDY DESIGN: We compared
      retrospective case series with historical controls. SETTING: A tertiary referral
      center--the ambulatory clinic at The University of Pittsburgh Medical Center.
      PATIENTS: The study consisted of 28 patients with Meniere's disease who failed
      conventional medical therapy and were offered gentamicin treatment or surgical
      intervention. Patients had to be followed for at least 2 years to be eligible for
      review. INTERVENTION: Intratympanic gentamicin solution injections were given by
      serial titration to the involved ear on a weekly or biweekly schedule. MAIN
      OUTCOME MEASURES: Adhering to the American Academy of Otolaryngology--Head and
      Neck Surgery 1985 criteria for reporting treatment results in Meniere's disease,
      the hearing status, control of vertigo, and disability scores using intratympanic
      gentamicin therapy were reported and compared with historical controls. RESULTS:
      Complete or substantial control of vertigo was achieved in 91% of patients.
      Hearing loss occurred in approximately one third of patients. Historically,
      similar hearing loss occurs in patients who were treated successfully, either
      medically or surgically. Ototoxicity (high frequency hearing loss) was more
      likely to be seen in patients with pre-treatment 8,000 Hz hearing thresholds
      better than 65dB. CONCLUSIONS: Intratympanic gentamicin therapy given by serial
      titration injections provides significant control of vertigo without the
      significant cost and potential morbidity of a more invasive surgical procedure.

PMID- 8989953
TI  - Cochlear microphonics in Meniere's disease.
AB  - The pathophysiology of hearing deterioration in Meniere's disease (MD) is
      unclear. Hair cell loss has been proposed to be the cause of severe hearing loss
      in Meniere's disease. The cochlear microphonic (CM) is known to be the receptor
      potential of the outer hair cells in the cochlea. This study measured the CM in
      Meniere's disease and investigated its relationship with the degree of hearing
      impairment and endolymphatic hydrops. Transtympanic electrocochleography (ECoG)
      using rarefaction (RAR) and condensation (CON) tonebursts at 1 kHz was performed
      on 130 ears of 119 patients. Ninety six ears were diagnosed to have MD and 34
      were diagnosed non-Meniere's disease (NMD). The mean amplitude of the CM was
      33.10 +/- 46.04 microV in the MD group and 13.15 +/- 12.77 microV in the NMD
      group (p < 0.001). Enlarged negative summating potential and action potential
      ratios (SP:AP > 40%) were found in 81.3% of the MD group and 17.6% of the NMD
      group. In the MD group, the CM in the group with an enlarged negative SP was
      36.98 +/- 49.78 microV, and 16.31 +/- 15.88 microV in the group without (p <
      0.01). The CM was 34.33 +/- 49.28 microV in the pure-tone average (PTA) < or = 25
      dB group, 46.97 +/- 58.31 microV in the 26-40 dB group, 29.12 +/- 42.62 microV in
      the 41-70 dB group, and 26.20 +/- 22.41 microV in the > 70 dB group (p > 0.05).
      The CMs in 11 pairs of MD ears and sensorineural hearing loss (SNHL) ears with
      matching hearing (MD 44 dB, SNHL 45 dB) were measured. They were 71.42 +/- 75.94
      microV and 7.90 +/- 5.89 microV, respectively (p < 0.01). Our study shows that
      the CM is higher in ears with endolymphatic hydrops, evidenced by an enlarged
      SP:AP ratio, than ears without and the CM shows no statistical difference in
      groups with different levels of hearing loss. These findings suggest that hearing
      loss with a large CM in Meniere's disease patients may be the result of an
      alteration of cochlear mechanics and only severe hearing loss with a small CM is
      caused by hair cell loss. The CM measurement, to evaluate the hair cell status,
      may be helpful in identifying patients whose hearing may be recoverable if the
      underlying hydrops can be corrected. Our data do not permit the conclusion that
      an enlarged CM can be used in the diagnosis of MD.

PMID- 8989954
TI  - Long-term effects of Meniere's disease on hearing and quality of life.
AB  - OBJECTIVE: To evaluate long-term hearing results and quality of life in patients
      with Meniere's disease. STUDY DESIGN: Detailed audiometric evaluation and disease
      specific as well as global health quality evaluation of patients with Meniere's
      disease. SETTING: Ambulatory evaluation was conducted in a large multispecialty
      clinic. PATIENTS: Meniere's disease in only one ear, were at least 1 year
      posttreatment, were < 65 years of age, had no neurologic or psychologic
      disorders, and lived within driving distance of the ambulatory clinic. MAIN
      OUTCOME MEASURES: Audiometry, the Hearing Handicap Inventory, Dizziness Handicap
      Inventory, Tinnitus Handicap Inventory, and SF-36 Health Survey. RESULTS: No
      statistically significant differences in long-term hearing results were detected
      from natural history in medically or surgically treated patients with Meniere's
      disease. A significant disease-specific symptom handicap was detected. The global
      health handicap was greater for emotional disability than for physical
      disability. CONCLUSIONS: Medical and surgical treatment does not significantly
      influence hearing results in Meniere's disease. Patients with Meniere's disease
      have a greater emotional disability than a physical disability.

PMID- 8989955
TI  - Triple semicircular canal occlusion versus labyrinthectomy in the cat.
AB  - HYPOTHESIS: We have theorized that surgical occlusion of all three semicircular
      canals (TCO) may be an effective means to treat vestibular pathology limited to
      semicircular canal dysfunction while preserving hearing and otolithic function.
      BACKGROUND: A procedure that would eliminate vertigo while preserving hearing and
      minimizing postoperative dysequilibrium would be desirable. METHODS: Staged
      bilateral TCO was performed on four cats and compared to staged bilateral
      labyrinthectomy in four cats. Balance and gait analysis were performed for 3
      weeks after each surgical procedure--a total of 6 weeks of testing. RESULTS:
      Balance testing, gait analysis, and righting reflex were found to be better among
      the cats undergoing TCO compared to labyrinthectomy. CONCLUSIONS: Compared to
      labyrinthectomy in the cat, TCO appears to have advantages for vestibular
      compensation after unilateral and contralateral surgery.

PMID- 8989956
TI  - Impact of vestibular disorders on fitness to drive: a census of the American
      Neurotology Society.
AB  - BACKGROUND: Legislation for reporting unfit-to-drive patients by physicians
      varies dramatically among U.S. states and Canadian provinces. The impact of
      vestibular disease on driving safety is not well described in the literature.
      OBJECTIVES: (1) to learn more about the critical issues and current practices of
      neurotologists regarding reporting of vestibular patients and (2) to make
      recommendations for reporting patients with vestibular disorders. STUDY DESIGN: A
      mailed census of members of the American Neurotology Society using a
      questionnaire based on a modified Dillman Total Design Survey Method. RESULTS:
      Most respondents are aware of the potential safety risks of patients who drive
      with vestibular diseases, most notably those with Tumarkins' attacks. Although
      many have counselled patients (94%) and considered reporting vestibular patients
      (75%), few actually have (14%). There was no consensus of opinion on a method of
      reporting unfit-to-drive patients. Only 18.9% of respondents supported mandatory
      physician reporting. Respondents who live in states where reporting is not
      mandatory and who are aware of this fact are (a) more satisfied with their
      state's legislation (chi 2 = 60.1, p = 0.001) and (b) less likely to report
      patients who they consider unfit-to-drive (chi 2 = 10.6, p = 0.03). CONCLUSIONS:
      In that there is no general consensus amongst respondents and the relative safety
      risks seem low in comparison to other disorders, at present we do not advocate
      mandatory reporting of patients with vestibular disorders.

PMID- 8989957
TI  - Saccular influence on the otolith-spinal reflex and posture during sudden falls
      of the cat.
AB  - HYPOTHESIS: The saccule provides important input for the otolith spinal reflex
      during sudden falls in the cat. BACKGROUND: Previous studies on cats have
      identified two distinct components of muscle activity in response to sudden
      falls: an early otolith-dependent component (OSR) and a later nonlabyrinthine
      component associated with landing. The presence of an otolith-dependent reflex
      suggests a discrete role of the otolith organs in the control of posture and
      locomotion. METHODS: The influence of saccular input on the OSR during sudden
      falls was studied by simultaneous video and electromyographic (EMG) recordings
      obtained from saccular-deficient deaf white cats and white cats with normal
      hearing. RESULTS: A total of 628 sudden falls from five cats (two normal, one
      unilaterally deaf and two bilaterally deaf) were studied. Normal cats had a total
      of 337 drops, 276 of which (82%) were acceptable; a unilaterally deaf cat had a
      total of 79 drops, 56 of which (71%) were acceptable; deaf cats had a total of
      212 drops, 177 of which (83%) were acceptable. The earliest of five observed
      behavioral events was that of forelimb extension which had a mean latency of 98
      +/- 32 msec in normal cats and 139 +/- 28 msec in deaf cats (p < 0.0001). The
      mean latency of early EMG activity in normal cats was 19 +/- 7 msec and in deaf
      cats was 30 +/- 13 msec (p < 0.0001). The unilaterally deaf cat exhibited
      behavior and early EMG responses that were similar to those of normal cats. Deaf
      cats displayed poor body control during landings that improved with experience.
      CONCLUSIONS: These data demonstrate that the saccule provides important input for
      the otolith spinal reflex in the cat, and cats that lack both saccules have
      discernible behavioral and EMG differences in response to sudden falls, when
      compared with normal cats.

PMID- 8989958
TI  - Vestibular evaluation in patients with early multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic, debilitating disease characterized by
      multiple areas of focal demyelination that develop throughout the white matter of
      the central nervous system at varying times. Most patients report disequilibrium
      at some point in the course of their disease. When balance disturbance occurs
      early in the course of the disease prior to diagnosis, the patient may present to
      the otolaryngologist for evaluation. Are there any patterns of balance
      dysfunction that might suggest the diagnosis to the evaluating physician? An
      evaluation of ten patients with known early MS suggests that platform
      posturography and ENG is the test most likely to provide useful diagnostic
      information in patients with early MS.

PMID- 8989959
TI  - Endolymphatic sac obliteration for large vestibular aqueduct syndrome.
AB  - The objective of this study was to investigate the effects of endolymphatic sac
      obliteration for stabilization of progressive hearing loss in patients with the
      large vestibular aqueduct syndrome. This was a retrospective case review
      conducted at a private neurootologic office in a metropolitan area. Seven ears in
      six patients were subjected to surgery for obliteration of the endolymphatic sac
      in an effort to stabilize progressive hearing loss associated with the large
      vestibular aqueduct syndrome. The study population was composed of four boys and
      two girls 4-17 years of age. The large vestibular aqueduct was unilateral in two
      patients and bilateral in four patients. All seven ears demonstrated progressive
      sensorineural hearing loss preoperatively. Surgical tissue obliteration was
      performed via a transmastoid approach in seven ears. The main outcome measure was
      comparison of pre- and postoperative hearing levels and stability. Magnetic
      resonance imaging also was performed in all cases at least 6 months
      postoperatively to determine patency of the endolymphatic sac and vestibular
      aqueduct. Six of seven ears maintained stable hearing during the follow-up
      period, which ranged from 6 months to 6 years (mean 3.2 years). One patient
      showed continued progression of hearing loss postoperatively. All seven ears
      demonstrated continued obliteration on postoperative imaging studies. Surgical
      obliteration of the endolymphatic sac may stabilize hearing in patients with the
      large vestibular aqueduct syndrome and progressive hearing loss. These results
      support the theory of pressure or fluid reflux into the labyrinth as a cause of
      progressive hearing loss in these patients.

PMID- 8989960
TI  - Does computerized dynamic posturography help us care for our patients?

PMID- 8989961
TI  - Utility of posturography in management of selected conditions that cause
      dizziness.

PMID- 8989962
TI  - Developmental anatomy of the supratubal recess in temporal bones from fetuses and
      children.

PMID- 8989963
TI  - Far field auditory brainstem response in neurotologic surgery.

PMID- 8989964
TI  - Auditory brainstem response audiometry and acoustic neuromas.

PMID- 8989965
TI  - CT imaging of the opaque shunt catheter.

PMID- 8989966
TI  - Doctor of audiology program.

PMID- 8989967
TI  - Absorbable Adams-DeWeese caval clip: an experimental study.
AB  - Adams-DeWeese caval clips have been shown to be effective in preventing pulmonary
      embolism. However, the use of Teflon clips constitutes a permanent solution for
      this transient risk. We tested an absorbable caval clip made of currently
      available synthetic biodegradable polymers in five female beagle dogs. The
      polymer used was PLA 96 containing 96% L lactic acid and 4% D lactic acid. After
      placement through a laparotomy, clips were routinely inspected and samples of the
      material were collected at regular intervals between 3 and 19 months
      postoperatively. The characteristics of absorption of PLA 96 in the
      retroperitoneal space were the same as those previously described in the
      literature. The clip retained its shape, rigidity, and effectiveness for 7
      months. Complete degradation of the clip took between 18 and 19 months.
      Absorption did not cause a major inflammatory reaction and had no thrombogenic
      effect. Given the small number of animals studied, these results must be
      considered preliminary.

PMID- 8989968
TI  - Outpatient management of superficial venous insufficiency at a naval medical
      facility.
AB  - Superficial venous insufficiency is common in a young, working population. It can
      result in disability and lost time from work because of chronic pain,
      inflammation, and/or ulceration. We reviewed our experience in the management of
      104 patients with superficial venous insufficiency secondary to saphenofemoral
      and/or perforator venous incompetence. The main treatment objective was to
      control venous insufficiency in a manner that would allow a rapid return to duty.
      The technique involved ligation of the incompetent saphenofemoral junction and/or
      perforating veins (i.e., point ligation) under local anesthesia. Patients
      returned to normal duty status the day after treatment. Six weeks later any
      persistent disease was controlled with compression sclerotherapy. Significant
      morbidity included postoperative wound complications in 4% and thrombophlebitis
      in 14%. Objectives of treatment, with excellent functional and cosmetic results,
      were achieved. True recurrence was noted in 8% of patients, whereas new disease
      developed in only 4%; the total recurrence rate was 12%. This mode of therapy is
      ideally suited to outpatient management. This study demonstrates the excellent
      control of venous dysfunction that is achievable with the use of selective
      therapy based on proximal venous ligation and staged sclerotherapy.

PMID- 8989969
TI  - Early attachment of platelets, leukocytes, and fibrinogen in endothelial cell
      seeded Dacron grafts.
AB  - Endothelial cell seeding has been advocated as a method for reducing the
      thrombogenicity of prosthetic grafts. Principally two different techniques for
      endothelial cell seeding can be used: immediate seeding of grafts followed by
      implantation or initial growth and establishment of an endothelial cell-covered
      surface before subsequent late implantation. This study was designed to determine
      whether the immediate seeding technique altered thrombogenicity directly after
      graft implantation. Carotid arteries from 19 sheep were replaced with Dacron
      interposition grafts; one side was seeded with endothelial cells and the other
      side was left unseeded. The dynamics of thrombus formation involving radiolabeled
      platelets, leukocytes, and fibrinogen were studied for 4 hours with flow reduced
      to 35 ml/min. No difference in platelet uptake (approximately 6-fold increase
      compared to baseline values) was found between endothelial cell seeded and
      unseeded grafts. Likewise, there were no differences in leukocyte uptake
      (approximately 4-fold increase) or fibrinogen uptake (approximately 10- to 15
      fold increase) between the two groups. No differences were demonstrated with
      regard to patency or thrombus weight. In this experimental investigation we were
      unable to verify any change in the uptake of platelets, white blood cells, or
      fibrinogen between endothelial cell seeded and unseeded Dacron grafts during the
      first 4 hours after graft placement. Immediate seeding does not affect the
      initial thrombogenicity of grafts.

PMID- 8989970
TI  - The validity of current vascular imaging methods in the evaluation of aortic
      anastomotic aneurysms developing after abdominal aortic aneurysm repair.
AB  - The aim of this cross-sectional study was to evaluate the validity of current
      imaging methods for diagnosing anastomotic false aneurysms (AFA) of the aorta.
      One hundred four patients who had undergone elective abdominal aortic aneurysm
      repair between January 1, 1985, and May 31, 1991, were studied. All of them were
      investigated for potential development of an aortic anastomotic aneurysm by B
      mode ultrasonography, CT scanning, digital subtraction arteriography, and MRI.
      These findings were compared with results of color-coded Doppler imaging, which
      is considered the "gold standard," and were subsequently classified as true
      positive or true negative. The accuracy of color Doppler ultrasound was
      independently evaluated by clinical examination of the patients, which was
      carried out for a mean period of 77.5 months during follow-up. On the basis of
      the data obtained and observations made during follow-up (mean 36.4 months), the
      sensitivity and specificity of the preceding imaging methods were estimated.
      Aortic anastomotic aneurysms were detected in two patients (1.9%). The
      sensitivity of all methods was 100% and specificity was as follows: 74.2% for
      ultrasound, 59.8% for nonenhanced CT scans, 85.4% for enhanced CT scans, and 99%
      for digital subtraction arteriograms. Color Doppler and MRI were 100% specific
      for ruling out aortic anastomotic aneurysms. In a comparison of the accuracy,
      estimated cost, safety, and the availability of each method, color Doppler
      appeared to be the diagnostic method of choice for identifying aortic anastomotic
      aneurysms after abdominal aortic aneurysm repair.

PMID- 8989971
TI  - Young women with advanced aortoiliac occlusive disease: new insights.
AB  - We identified a group of 24 young (less than 50 years of age) women with
      isolated, premature atherosclerotic aortoiliac occlusive disease and attempted to
      identify distinguishing hemostatic characteristics. Most of these patients (62%)
      presented with acute thromboembolic events (blue toe syndrome, n = 6;
      macroemboli, n = 6; or aortoiliac thrombosis, n = 3). Aortoiliac reconstruction
      (aortoiliac endarterectomy, n = 10, aortobifurcation bypass grafts, n = 6; and
      percutaneous angioplasty, n = 4) was complicated by early thrombosis in 6 of 20
      cases (30%), (1 of 10 endarterectomies, 4 of 6 bypass grafts, and 1 of 4
      angioplasties). Fresh thrombus overlying an atherosclerotic plaque was a common
      finding at surgery. This observation and the relatively high incidence of
      thromboembolic events led us to hypothesize that a characteristic hemostatic
      profile might underlie the remarkably similar clinical presentations of these
      women. Levels of antiphospholipid antibodies (anticardiolipin antibodies and
      lupus anticoagulant), plasminogen activator inhibitor-1, fibrinogen, antithrombin
      III, protein C, protein S, plasminogen, prothrombin fragment F1 + 2, and D-dimer
      were determined for these young women and for 21 age-matched white female control
      subjects without vascular disease and nine white male patients with aortoiliac
      occlusive disease (mean 61 years, range 43 to 74 years). The incidence of
      anticardiolipin antibodies was 42% (8 of 19) in the female patients, which was
      significantly elevated (p = 0.028). The female (62.5%) and male (100%) patients
      had significantly elevated D-dimer levels (p < 0.001). Deficiencies of
      antithrombin III, protein C, and protein S were rare. A unique pattern of
      premature aortoiliac atherosclerosis exists in some young women. Intra-arterial
      thromboembolic events are common at presentation and complicate surgical
      management. The role of antiphospholipid antibodies remains uncertain.

PMID- 8989972
TI  - Is hyperbaric oxygen a useful adjunct in the management of problem lower
      extremity wounds?
AB  - Hyperbaric oxygen (HBO) is currently being used in the treatment of nonhealing or
      "problem" wounds of the lower extremities. In an attempt to evaluate the efficacy
      of HBO in problem wounds, a retrospective study of the HBO experience at Orlando
      Regional Medical Center was conducted. From 1989 to 1994, fifty-four patients
      with nonhealing lower extremity wounds resulting from underlying peripheral
      vascular disease and/or diabetes mellitus were treated with HBO. Wounds were
      grouped into the following five categories: (1) diabetic ulcers (n = 17 [31%]);
      (2) arterial insufficiency (n = 8 [15%]); (3) gangrenous lesions (n = 6 [11%]);
      (4) nonhealing amputation stumps (n = 13 [24%]); and (5) nonhealing operative
      wounds (n = 10 [19%]). Each patient received an average of 30 treatments.
      Outcomes for all 54 patients treated with HBO in this study were dismal. None of
      the patients experienced complete healing, six (11%) showed some improvement, 43
      (80%) showed no improvement, and in five cases (9%) results were inconclusive
      because these patients underwent concomitant revascularization or amputation.
      Thirty-eight of the 43 patients who showed no improvement (88%) ultimately
      required at least one surgical procedure to treat their wounds. Thirty-four
      patients (63%) developed complications, most commonly barotrauma to the ears,
      which occurred in 23 patients (43%). The average cost of 30 HBO treatments was
      $14,000 excluding daily inpatient charges. Based on the experience with HBO
      therapy at Orlando Regional Medical Center and the paucity of good supporting
      literature, it is difficult to justify such an expensive, ineffective
      complication-prone treatment modality for problem extremity wounds.

PMID- 8989973
TI  - A comparison of outcome criteria in the diagnosis of renovascular hypertension.
AB  - The outcome criteria used for the diagnosis of renovascular hypertension (RVHT)
      following renal revascularization have not been validated. Differing criteria of
      indeterminate accuracy have yielded conflicting conclusions concerning the
      prevalence and efficacy of treatment of RVHT. We compared the accuracy of
      conventional outcome criteria used in the diagnosis of RVHT to that of novel,
      ordered outcome analysis to determine whether such an analysis might provide a
      more consistent means of diagnosing RVHT. Twenty-seven patients underwent
      intervention for treatment of presumed RVHT (group I), and 40 patients with
      presumed essential hypertension were treated with antihypertensive medication
      alone (group II). A standard dichotomized (improved or unimproved) outcome scheme
      and a five-level, ordered outcome scheme (ranging from definitely unimproved to
      definitely improved) were used to generate nominal outcomes of therapy for each
      patient. The resultant outcome groups were examined to determine the effect of
      such partitioning on blood pressure and medication requirements. To determine
      their diagnostic accuracy, the conventional and ordered outcome schemes were
      compared with a consensus outcome scheme derived from the use of numerous
      criteria. Significant correlations were observed between the ordered outcome
      score and posttreatment reductions in systolic blood pressure (r = 0.53, p =
      0.007), diastolic blood pressure (r = 0.74, p = 0.0001), and medication score (r
      = 0.71, p = 0.0001). Overall diagnostic accuracy was estimated to be 91% for
      ordered criteria and 85% for dichotomized criteria. Correlation of the ordered
      and conventional schemes' assignments with the consensus scheme's assignments was
      0.79 (p = 0.0001) and 0.63 (p = 0.0001), respectively. A simple, ordered outcome
      scheme compares favorably with the standard dichotomized scheme in assigning a
      diagnosis of RVHT to patients following renal revascularization or nephrectomy.
      The ordered scheme offers the advantages of simplicity and accuracy over current
      schemes.

PMID- 8989974
TI  - Multiple mycotic pseudoaneurysms due to Yersinia enterocolitica: report of a case
      and review of the literature.
AB  - The etiology of mycotic aneurysms is variable but most often includes
      streptococci, staphylococci, Salmonella, and Pseudomonas infections. Yersinia
      enterocolitica is an organism that has been infrequently associated with vascular
      infections. We report a case of two ruptured mycotic pseudoaneurysms occurring in
      the same patient in the superficial femoral artery and the infrarenal abdominal
      aorta only 10 days apart. The literature is reviewed, and the clinical findings
      and pathology are discussed. The unique problem of multiple mycotic aneurysms
      developing at different times as a result of Yersinia bacteremia suggests the
      need to monitor these patients longitudinally and evaluate multiple sites on the
      arterial tree to detect occult pseudoaneurysms and prevent late death from
      rupture.

PMID- 8989975
TI  - Popliteal aneurysm due to fibromuscular dysplasia.
AB  - We report herein the case of an asymptomatic popliteal aneurysm due to
      fibromuscular dysplasia in a 39-year-old woman. The aneurysm was resected and
      arterial continuity restored by direct end-to-end anastomosis. Pathologic
      findings were consistent with fibromuscular dysplasia of the media. To the best
      of our knowledge, this is the fourth case documented by pathologic findings in
      the literature.

PMID- 8989976
TI  - Superior mesenteric venous aneurysm.
AB  - The case of a 50-year-old woman with an extremely rare venous malformation of the
      portal venous system is reported. The patient presented with a true aneurysm of
      the superior mesenteric vein, which has thus far been reported in no more than
      eight cases worldwide. This malformation may be congenital or acquired. Secondary
      aneurysms are thought to be due to liver disease, portal hypertension, trauma, or
      inflammation. Aneurysms of the portomesenteric venous system may be asymptomatic
      or give rise to severe, often dramatic conditions such as crampy abdominal pain,
      jaundice, and upper gastrointestinal hemorrhage secondary to portal hypertension.
      The diagnosis is usually made by ultrasound (B-mode or color flow Doppler), CT
      scan, and MRI. Invasive procedures such as venous phase mesenteric arteriography
      or splenoportography may be helpful in confirming it. In our opinion aneurysms of
      the portal venous system, even if they are congenital and (still) asymptomatic,
      require early surgical control because the prognosis for patients with these
      aneurysms is unpredictable and potential complications (e.g., portal
      hypertension, fistula, contained perforation, or rupture) may be fatal. In the
      case presented the mesenteric venous aneurysm was resected and the confluent
      veins were reconstructed.

PMID- 8989977
TI  - Balloon angioplasty and stent placement during operative vascular reconstruction
      for lower extremity ischemia.

PMID- 8989978
TI  - Containers, mental space and psychodynamics.
AB  - The concept of the container has a place within cognitive science as well as
      within psychodynamic theories. Cognitive semantics has shown that many metaphors
      giving meaning to daily life-events use the container as a basic reference point.
      Psychoanalytic theory, most notably, Freud's psychosexual developmental model,
      illustrates how the container of the body results in meaning. Object relations
      theory in psychoanalysis has shown how patients with borderline personality
      disorder behave according to the dynamics of container and containment. Both the
      cognitive and the psychodynamic conceptions of containers are clinically
      relevant. The fundamental notion of the container leads to an exploration of
      'container dynamics' both in cognitive semantics and in psychodynamic work. A
      model of the cusp may be of help in the description of the dynamics at the border
      of the container. Furthermore, the descriptions of the patient's communication of
      emotion and thoughts may involve three interacting dimensions: an effective
      perceptual dimension, a phantasy dimension and a socio-interactive dimension. The
      interaction between these dimensions has implications for dealing with container
      dynamics and the process of containment.

PMID- 8989979
TI  - A process view of the self.
AB  - This paper further develops the concept of the self as experiential being, and
      its relevance for an understanding of psychopathology. It is proposed that the
      self, or 'I', processes and regulates its experiences by means of three
      modalities that are dynamically interrelated throughout life:
      exchanges/boundaries, internal mirroring/affective awareness, and the
      representational space. It is further proposed that pathology develops when these
      processes of self-regulation go wrong. As a result, different psychopathological
      positions are identified which, in the case of severe disorders, require a
      distinctive initial approach to therapy.

PMID- 8989980
TI  - The grief response in the partners of women who miscarry.
AB  - Research over the last two decades has revealed that significant psychological
      effects may ensue for women who suffer spontaneous abortion. The psychological
      impact on their male partners has been largely overlooked. This paper examines
      the psychological impact on the male partners of 126 British women who suffered
      miscarriage. Higher than anticipated levels of grief and stress were found on the
      Perinatal Grief Scale and the Impact of Events Scale respectively, indicating
      that these men were strongly affected by the miscarriage. The duration of the
      pregnancy prior to miscarriage, and the experience of confirmatory imaging of the
      foetus via routine ultrasound scan, were factors related to raised levels of
      grief and stress. A small number of semi-structured interviews appeared to
      confirm that some men displayed symptoms of Bowlby's (1961) first stage of
      bereavement. These were modified by differences in the expected role behaviour of
      men, but in other respects were comparable to the findings of a recent study of
      an Australian cohort of women who miscarried (Conway, 1995).

PMID- 8989981
TI  - How does marriage protect women with histories of affective disorder from post
      partum relapse?
AB  - Interviews were carried out at 36 weeks antenatal with 63 married couples, in 36
      of which the woman had a history of affective disorder and in 27 the woman had no
      previous psychiatric history. The men's attitudes to their wives were assessed
      using expressed emotion methodology. Also assessed were psychiatric history,
      neuroticism, satisfaction with the marital relationship and attitudes to sex,
      pregnancy and parenthood in both the woman and her partner. Women with
      psychiatric histories who did not relapse in the six months following delivery
      had partners who were more positive about them than partners of high-risk women
      who remained well and control women. This effect is explored further by examining
      which characteristics of the man and which of the woman contributed to his
      critical and positive comment score. Criticism of his wife was associated with
      each partner reporting less marital satisfaction and also with the man's
      psychiatric history. No characteristic of the woman contributed to her partner's
      criticism. In contrast, the men's positive comments about their wives were
      associated with the woman's satisfaction with key aspects of her femaleness.
      Positive husbands had wives were pleased to be pregnant, happy with their
      pregnant bodies and enjoying the sexual aspect of the marital relationship. In
      women with psychiatric histories the time which had elapsed since her last
      psychiatric admission also influenced his positive comments.

PMID- 8989982
TI  - Eating attitudes in young females with diabetes: insulin omission identifies a
      vulnerable subgroup.
AB  - Eating attitudes were investigated in young females with diabetes (YFDs) and
      healthy age-matched female controls. Results from the Eating Disorder Inventory
      confirmed that YFDs had higher scores for drive for thinness, body
      dissatisfaction and bulimia. In addition, YFDs who omitted insulin injections had
      high scores for ineffectiveness and interoceptive awareness and had increased
      sensitivity to external eating cues (as measured by the Dutch Eating Behaviour
      Questionnaire). It is suggested that dieting and weight gain associated with
      diabetes treatment precipitate a deterioration in eating attitudes. Furthermore,
      omission of insulin and increased sensitivity to external eating cues serve as
      markers for a group of YFDs who are at increased risk of developing an eating
      disorder. The present results provide support for the spiral model of eating
      disorders (Heatherton & Polivy, 1992) and its emphasis on the importance of self
      esteem and self-awareness.

PMID- 8989983
TI  - Causal beliefs and acute psychiatric hospital admission.
AB  - Causal beliefs regarding the onset of psychiatric disorder and treatment
      expectations for clients admitted to a psychiatric unit were examined from the
      points of view of the clients themselves, their relatives and staff. Results
      suggested that these beliefs were influenced by the admission itself. Those
      clients who had been admitted previously held significantly higher biological
      causal beliefs than those who had been admitted for the first time; as compared
      to staff who did not distinguish between the two groups in this way. The mean
      psychosocial views of relatives decreased significantly over the two-month period
      following an admission. Clients' and relatives' mean biological views were
      significantly greater than those of staff. Various correlations were found
      between causal beliefs and treatment expectations including one in the
      relative's' view between psychosocial causal beliefs and the importance assigned
      to family therapy. Indeed, there was a significant decrease in the family therapy
      rating over time given by relatives.

PMID- 8989984
TI  - Monitoring of intrusions in post-traumatic stress order: a report of single case
      studies.
AB  - The effect of monitoring on frequency and duration of intrusions, and on reported
      symptomatology in patients with a diagnosis of post-traumatic stress disorder
      (PTSD) was investigated. Six patients were asked to monitor their intrusions over
      a period of two months. The patients were reassessed after completing the
      monitoring and followed up after three months. Four patients recovered and no
      longer met criteria for PTSD, one patient was still experiencing some symptoms,
      and one still met criteria for a diagnosis of PTSD.

PMID- 8989985
TI  - Intracultural variation in causal accounts of diabetes: a comparison of three
      Canadian Anishinaabe (Ojibway) communities.
AB  - This paper presents a methodological approach for examining variation and
      consensus both within and between research settings and for addressing issues of
      generalizability and replicability. The comparison is based on how individuals
      diagnosed with diabetes and living in three Canadian Anishinaabe (Ojibway)
      communities explain diabetes and talk about their responses to the illness. Two
      kinds of interview format are used--an open-ended explanatory model type
      interview and a more structured, true-false, interview, amenable to analysis with
      cultural consensus theory. The responses given in both interviews converge on a
      set of explanations which can be found in all three communities, although
      differences occur in how these explanations are framed and emphasized.
      Implications of these differences and how these accounts relate to how
      individuals respond to diabetes are discussed. It is argued that the analysis of
      both interview formats leads to a deeper and more finely nuanced representation
      of understandings about causes of diabetes across the three communities than
      could be achieved by using one alone.

PMID- 8989986
TI  - Cultures in psychiatric nosology: the CCMD-2-R and international classification
      of mental disorders.
AB  - This essay reviews the Chinese Classification of Mental Disorders, Second
      Edition, Revised (CCMD-2-R, 1995), by assuming the theoretical stance that
      symptom recognition, disease construction, and taxonomic strategy in psychiatry
      reflect, and are constrained by, the cultural norms and values as well as the
      political and economic organizations of the society in which they are embedded.
      The CCMD-2-R is an ethnomedical classification grounded in both symptomatology
      and etiology, in which Chinese psychiatrists seek to conform with international
      classifications on the one hand, and to sustain a nosology with Chinese cultural
      characteristics on the other. Although broad similarities between the ICD-10 and
      CCMD-2-R are evident, their blending is legitimately incomplete. Thus, the
      particular additions (e.g., travelling psychosis, qigong induced mental
      disorders), deletions (e.g., somatoform disorders, pathological gambling, a
      number of personality and sexual disorders), retentions (e.g., unipolar mania,
      neurosis, hysteria, homosexuality), and variations (e.g., depressive neurosis,
      neurasthenia) reveal not only the changing notions of illness but also the
      shifting social realities in contemporary China. The CCMD-2-R will be widely used
      by Chinese psychiatrists and should standardize diagnostic practice and
      facilitate research, but its impact on everyday clinical work and psychiatric
      training remains to be evaluated. For Western researchers, it is one avenue for
      achieving an understanding of the Chinese social world, and should usefully be
      contrasted with the ICD-10 and DSM-IV as the move towards an international
      nosology continues.

PMID- 8989988
TI  - The wounded spirit: a cultural formulation of post-traumatic stress disorder.

PMID- 8989987
TI  - Alcoholism, a contagious disease. A contribution towards an anthropological
      definition of contagion.
AB  - The goal of this article is to show, from the discourses of drinkers' spouses,
      members of a "cured-drinkers" movement in France very different from the AA, what
      the idea of the contagious character of alcoholism means in the subjects'
      representations and by extension, what the idea of contagion may contain when
      seen from an anthropological perspective. This work rests on the observation that
      many people consider that their spouse's alcoholism makes them sick, and tend to
      identify with the sick person by finding effects of alcoholism on their own
      bodies. The notion of contagion qualifies here the perception of the impact of
      the other's sickness on oneself, by physical and social proximity to the drinker,
      insofar as the conditions for contagion to be possible include not only sharing
      the same physical (domestic) space, but also the existence of a social bond.

PMID- 8989989
TI  - Quality control in the United States.
AB  - On a per capita basis, PTCA is more than three times more prevalent in the United
      States than in any other country. The US has nearly 1,000 institutions and 7,000
      physicians doing angioplasty. Mortality and emergency bypass surgery rates are
      inversely proportional to angioplasty volume. Although PTCA is more prevalent in
      the United States, operators in other countries do more cases than do their US
      counterparts. Multiple forces control quality in the United States. Economic,
      political and legal forces are all important.

PMID- 8989990
TI  - Interleukin-2 gene transduction into freshly isolated lung adenocarcinoma cells
      with adenoviral vectors.
AB  - We evaluated the efficiency of gene transduction and of gene expression by
      adenoviral vectors in human lung adenocarcinoma cells. Freshly isolated cancer
      cells were collected from pleural effusions in adenocarcinoma patients by
      centrifugation with a Percoll gradient. Adenoviral vectors resulted in effective
      gene transduction into human lung cancer cell lines and into freshly isolated
      lung adenocarcinoma cells. In an experiment using the beta-galactosidase (LacZ)
      gene, the Adex1CA vector with a regulatory sequence of chicken beta-actin as
      promoter and an enhancer derived from cytomegalovirus produced a higher
      transduction ratio and greater expression levels than adenoviral vectors with
      other promoter systems. Transduction with Adex1CA vectors containing the human
      interleukin-2 (IL-2) gene (Adex1CAhIL-2) resulted in enhanced secretion of IL-2
      from gene-modified lung cancer cells. Treatment with normal human serum inhibited
      gene transduction by Adex1CAhIL-2 but did not inhibit gene expression after
      transduction by Adex1CAhIL-2. The secretion of IL-2 from the gene-modified cells,
      which were irradiated at 100 Gy before transduction, continued for 8 days. In a
      mouse model, the intrapleural injection of IL-2 gene-modified 3LL cells
      transduced by Adex1CAhIL-2 could cure the pre-existing lung tumours with
      malignant pleural effusions to induce tumor-specific immunity. But these
      therapies did not show any therapeutic benefit on the pre-existing tumor in
      subcutaneous region. These data suggest a potentially useful but limited clinical
      role of Adex1CAhIL-2 in gene therapy for lung cancer patients.

PMID- 8989991
TI  - Aerosol administration of a recombinant adenovirus expressing CFTR to cystic
      fibrosis patients: a phase I clinical trial.
AB  - Ad CFTR, a replication-deficient adenovirus expressing the human cystic fibrosis
      transmembrane conductance regulator (CFTR), was administered by aerosolization in
      a single escalating dose to three pairs (cohorts) of cystic fibrosis (CF)
      patients. Buffer only was administered to the nose and lungs 9-14 days before
      nasal instillation of virus followed the day after by aerosolization of Ad CFTR
      to the lung. Nasal doses (defined in terms of viral plaque forming units, pfu)
      were 10(5), 10(7), and 4 x 10(8), whereas aerosolized doses were 10(7), 10(8),
      5.4 x 10(8) for each cohort, respectively. No acute toxic effects were observed
      in the first 4 weeks after virus treatment. Shedding of infectious Ad CFTR was
      never detected, whereas detection of vector DNA sequences and CFTR expression
      demonstrated DNA transfer to the nose and airways of patients. No significant
      deviations in immunological and inflammatory parameters were observed in serum
      and in bronchoalveolar lavage (BAL). Importantly, for all patients, the serum
      anti-adenovirus antibody levels did not change significantly from baseline and no
      antibodies against adenovirus were found in BAL.

PMID- 8989992
TI  - Transplantation of Gunn rats with autologous fibroblasts expressing bilirubin UDP
      glucuronosyltransferase: correction of genetic deficiency and tumor formation.
AB  - The end product of the breakdown of the heme group of hemoglobin and other heme
      containing proteins is bilirubin. Bilirubin is hydrophobic and cannot be excreted
      as such. Therefore, mammals have a liver enzyme bilirubin UDP
      glucuronosyltransferase (B-UGT), which conjugates bilirubin with glucuronic acid,
      thereby making the molecule much more water soluble. Bilirubin glucuronides are
      secreted into bile. Patients with Crigler-Najjar (CN) disease have a deficiency
      in bilirubin UDP-glucuronosyltransferase and accumulate high serum levels of
      bilirubin. An animal model for CN disease is the Gunn rat. The obvious target for
      gene therapy for CN disease is the liver, but because liver cells do only divide
      infrequently, they are difficult to transduce. To investigate whether cells that
      are easily transduced can be used to develop gene therapy for CN disease, we have
      transduced Gunn rat fibroblasts with B-UGT, using a recombinant retrovirus. Gunn
      rat fibroblasts expressing B-UGT were able to glucuronidate bilirubin present in
      cell culture media. In this study, we describe the intraperitoneal
      transplantation of Gunn rats with Gunn rat fibroblasts expressing B-UGT.
      Transplantation of the fibroblasts corrected the genetic deficiency of the Gunn
      rats, serum bilirubin concentrations of the transplanted Gunn rats were reduced
      to normal, and bilirubin glucuronides appeared in bile. However, due to the
      prolonged period of cell culture, the transplanted fibroblasts were transformed,
      and the experimental animals developed tumors after transplantation.

PMID- 8989993
TI  - Innate immune mechanisms dominate elimination of adenoviral vectors following in
      vivo administration.
AB  - To evaluate the contribution of the innate immune component of host defense in
      clearing the genome of adenovirus (Ad) vectors following in vivo administration,
      the Ad vectors AdCMV.beta gal (expressing beta-galactosidase) or AdCMV.Null
      (expressing no gene) were administered intravenously to immunocompetent or
      immunodeficient mice, and the amount of vector genome was quantified in the
      liver. Strikingly, 90% of vector DNA was eliminated within 24 hr. There was no
      increase in vector DNA in other tissues over this period, suggesting that rapid
      clearance of vector genome resulted from local degradation. After 24 hr, vector
      elimination was slow, with only 9% of the initial amount of vector genome cleared
      over the subsequent 3 weeks. Importantly, early phase (0-24 hr) elimination of
      vector DNA was independent of the transgene and similar in immunocompetent and
      nude animals. These observations suggest two phases of Ad vector elimination: a
      previously recognized late, immune-related elimination, and the early, innate
      immune elimination described in the present study. The early phase of vector loss
      is, by far, the dominant mechanism, an observation that has implications in
      developing strategies to maintain persistent expression of the newly transferred
      gene following in vivo gene therapy.

PMID- 8989994
TI  - Characterization of factors involved in modulating persistence of transgene
      expression from recombinant adenovirus in the mouse lung.
AB  - One potential limitation of adenovirus (Ad)-based vectors for the gene therapy of
      cystic fibrosis (CF) and other genetic diseases is the transience of expression
      observed in most in vivo systems. In this study, the influence of various factors
      on persistence of transgene expression in the lung was investigated. In the
      absence of immune pressure, such as in the nude mouse, the genomic structure of
      the vector was found to be predominant in determining the persistence of
      expression; Ad vector constructs with an E1-E3+E4ORF6+ backbone encoding beta
      galactosidase (beta-Gal) or the cystic fibrosis transmembrane conductance
      regulator (CFTR) produced declining levels of expression while an Ad/CMV beta Gal
      vector with an E1-E3+E4+ backbone gave rise to sustained, long-term reporter gene
      expression. The ability of the latter vector to persist was in turn limited in
      part by the presence of cytotoxic T lymphocytes (CTLs). Adoptive transfer
      experiments indicated that CTLs directed against either viral proteins or the
      beta-Gal reporter gene product were able to reduce expression in nude C57BL/6
      mice stably expressing beta-Gal from the E4+ vector. Finally, the specificity and
      strength of the CTL response elicited by Ad vector was found to vary considerably
      depending on mouse strain haplotype. These results indicate that persistence of
      transgene expression in a given system is determined by the interplay between
      several factors including genomic structure of the vector, host background, and
      immune response.

PMID- 8989995
TI  - Two-step delivery of retroviruses to postmitotic, terminally differentiated
      cells.
AB  - Recombinant replication-defective retroviral vectors are currently the most
      commonly used vectors for introducing foreign genes into human cells in gene
      therapy protocols. Their genomes stably incorporate in the host chromosomes of
      mitotic cells, thus ensuring stable expression. However, the applications of
      retroviruses to gene therapy are limited by their inability to infect postmitotic
      cells such as muscle fibers. In an attempt to overcome such limitations, we have
      developed a novel two-step transduction protocol that allows integration and
      expression of retroviral genes in differentiated cells. We induced DNA synthesis
      in terminally differentiated cultured mouse myotubes derived from both
      established myogenic cell lines and from primary myoblasts. We infected the
      postmitotic cells with a recombinant replication-defective adenoviral vector
      encoding the SV40 large T antigen as a mitogen. Subsequently we transduced the
      adenovirus-infected cells with a Moloney retroviral vector bearing the LacZ gene.
      Histochemical analysis revealed the coincident expression of LacZ gene in those
      myotubes that had been induced to synthesize DNA.

PMID- 8989996
TI  - In vivo correction with recombinant adenovirus of 4-hydroxyphenylpyruvic acid
      dioxygenase deficiencies in strain III mice.
AB  - Tyrosinemia type 3, caused by a genetic deficiency of 4-hydroxyphenylpyruvic acid
      dioxygenase (HPD) in tyrosine catabolism, is characterized by convulsion, ataxia,
      and mental retardation. The III mouse is a model of tyrosinemia type 3. HPD
      activity and protein are defective in the liver and its blood tyrosine levels are
      elevated, the range being between 1,100 and 1,656 microM. We constructed a
      recombinant adenoviral vector bearing the human HPD cDNA (AdexCAGhHPD), which is
      expressed under the control of a potent CAG promoter. III mice were injected with
      1.0 x 10(8) to 1.0 x 10(9) pfu of AdexCAGhHPD through the tail vein. When 3.0 x
      10(8) - 1.0 x 10(9) pfu were injected, blood tyrosine levels decreased within 3
      hr, reached a normal range (under 300 microM), and remained at a low level for 2
      6 weeks. Hepatic HPD activities also increased as early as 3 hr after the
      injection of 5.0 x 10(8) pfu, reached the levels comparable to the control mice
      in 3-7 days, and then decreased, and correlated well to blood tyrosine. Hepatic
      HPD expression was confirmed by Northern blot and immunoblot analyses. Histology
      revealed no difference (gross or microscopic) between the liver injected with
      AdexCAGhHPD and the control. No significant changes in blood tyrosine levels were
      noted after the second injection of 5.0 x 10(8) pfu of AdexCAGhHPD. Thus, the
      intravenous administration of the adenoviral vector bearing a foreign gene seems
      suitable for transient, early gene transfer into the liver.

PMID- 8989997
TI  - Glioma cells transduced with an Escherichia coli CD/HSV-1 TK fusion gene exhibit
      enhanced metabolic suicide and radiosensitivity.
AB  - To ascertain whether concomitant expression of Escherichia coli deaminase (CD)
      and herpes simplex virus type-1 thymidine kinase (HSV-1 TK) could mediate greater
      levels of cytotoxicity beyond that observed with either suicide gene alone, 9L
      gliosarcoma cells were transduced with a retrovirus encoding a CD/HSV-1 TK fusion
      gene. The resultant CD/HSV-1 TK fusion protein (CDglyTK) was found to be
      bifunctional via CD and HSV-1 TK enzymatic assays, and conferred upon cells
      prodrug sensitivities equivalent to or better than that observed for each enzyme
      independently (ganciclovir [GCV] and bromovinyldeoxyuridine [BVdU] for HSV-1 TK
      and 5-fluorocytosine [5-FC] for CD). Simultaneous treatment of CDglyTK-expressing
      cells with prodrugs specific for HSV-1 TK and CD (GCV/5-FC or BVdU/5-FC) resulted
      in slight synergistic toxicity, two- to three-fold greater than that expected if
      the cytotoxic effects of each prodrug were purely additive. More importantly, co
      treatment with HSV-1 TK- and CD-specific prodrugs was found to increase greatly
      the radiosensitivity of CDglyTK-expressing cells. Sensitivity enhancement ratios
      of 2.44 (GCV/5-FC) and 3.90 (BVdU/5-FC) were achieved. The results suggest that
      double suicide gene therapy, using a bifunctional CD/HSV-1 TK fusion gene,
      coupled with radiotherapy may provide a highly efficient means of selectively
      treating cancer.

PMID- 8989998
TI  - Replication of rep-cap genes is essential for the high-efficiency production of
      recombinant AAV.
AB  - Adenoassociated virus (AAV) has been developed as a vector for gene transfer
      because of its advantageous features: it is nonpathogenic, naturally replication
      defective; it infects growth-arrested cells, and can transfer the therapeutic
      gene without co-delivery of any viral genes. However, a major obstacle in
      conducting systematic studies of AAV-mediated gene transfer in animal models is
      the difficulty of obtaining large quantities of recombinant virus. Recent
      development of AAV packaging cell lines has simplified the procedure of producing
      recombinant AAV (rAAV). However, the efficacy of producing large quantities of
      rAAV with these cell lines is yet to be demonstrated. In this study we have
      analyzed the difference between the replication of wild-type AAV and the
      production of rAAV. Using a combined single-plasmid system that carries both an
      AAV vector and the rep-cap genes, we have demonstrated that the AAV vector
      replicates to high number of copies whereas the rep-cap sequences remain
      unamplified in the virus-producing cells, When the copy number of rep-cap genes
      was increased by varying the vector/rep-cap ratio in the transfection mixture,
      the titer of rAAV increased proportionally. Thus, the titer of rAAV is limited by
      the low copy number of the rep-cap genes that results in an insufficient
      expression of the Rep and Cap proteins. We have also shown that generation of
      double-stranded replicating form of the vector DNA is accompanied by an amplified
      transgene expression. We propose that the increased gene expression from the
      accumulating double-stranded viral DNA is likely to be the mechanism by which
      wild-type AAV produces a large number of particles necessary to package the self
      replicating AAV genomes. We conclude that mimicking this amplified expression of
      rep-cap genes may provide the key to produce high titers of rAAV.

PMID- 8989999
TI  - Circumvention of anti-adenovirus neutralizing immunity by administration of an
      adenoviral vector of an alternate serotype.
AB  - Effective gene transfer and expression following repetitive administration of
      adenoviral (Ad) vectors in experimental animals is limited by anti-Ad
      neutralizing antibodies. Knowing that anti-Ad humoral immunity is serotype
      specific, we hypothesized that anti-Ad neutralizing immunity could be
      circumvented using Ad vectors of different serotypes (Ad2, Ad5) within the same
      subgroup (C) to transfer and express beta-glucuronidase (beta glu) in the lung.
      Sprague-Dawley rats received an intratracheal administration of either Ad2 beta
      glu or Ad5 beta glu, and, 14 days later, repeat administration of either the same
      vector or a vector of a different serotype. Analysis of serum and bronchoalveolar
      lavage fluid following initial vector administration demonstrated systemic and
      local serotype-specific neutralizing antibodies. For both the Ad2 and Ad5
      vectors, beta glu expression 24 hr following the second administration of the
      same serotype was < 30% of that of naive animals. In contrast, beta glu
      expression 24 hr following second administration of a different serotype Ad
      vector was similar to expression at 24 hr of naive animals receiving a single
      administration (Ad5 beta glu followed by Ad2 beta glu, as well as Ad2 beta glu
      followed by Ad5 beta glu; p > 0.2 both comparisons). Although the alternative
      serotype bypassed anti-Ad neutralizing immunity, persistence of expression was
      reduced compared to that following administration to naive animals. Compatible
      with this observation, systemic administration of the same vectors to C57B1/6
      mice demonstrated induction of cytotoxic T lymphocytes directed against the beta
      glu transgene, as well as products of the Ad genome. Interestingly, intratracheal
      administration of vectors with different serotypes and different transgenes to
      rats resulted in longer expression (but still not normalized) compared to that
      achieved with vectors of different serotypes but the same transgene. These
      observations demonstrate that alternate use of Ad vectors from different
      serotypes within the same subgroup can circumvent anti-Ad humoral immunity to
      permit effective gene transfer after repeat administration, although the
      chronicity of expression is limited, likely by cellular immune process directed
      against both the transgene and viral gene products expressed by the vector.

PMID- 8990000
TI  - A phase I study of vaccination with autologous, irradiated melanoma cells
      engineered to secrete human granulocyte-macrophage colony stimulating factor.

PMID- 8990001
TI  - Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations.
AB  - Mut methylmalonic acidemia is caused by mutations in the MUT locus encoding the
      enzyme methylmalonyl CoA mutase. Genotypic and phenotypic variability in this
      disease has been studied extensively by biochemical and somatic cell genetic
      techniques, by molecular cloning, and by gene transfer. Mutations have been
      identified that cause classic mut(o) phenotypes in which there is no detectable
      enzymatic activity, mut- phenotypes in which there is residual cobalamin
      dependent activity, as well as a subset within both mut(o) and mut- phenotypes
      that exhibit interallelic complementation. These mutations illustrate the
      position, structure, and function of critical domains within this cobalamin
      binding enzyme and provide new insights into the biochemical and clinical
      consequences of enzyme deficiency.

PMID- 8990002
TI  - Molecular analysis of the APC gene in 105 Dutch kindreds with familial
      adenomatous polyposis: 67 germline mutations identified by DGGE, PTT, and
      southern analysis.
AB  - Germline mutations of the adenomatous polyposis coli (APC) gene are responsible
      for familial adenomatous polyposis (FAP), an autosomal dominant predisposition to
      colorectal cancer. We screened the entire coding region of the APC gene for
      mutations in an unselected series of 105 Dutch FAP kindreds. For the analysis of
      exons 1-14, we employed the GC-clamped denaturing gradient gel electrophoresis
      (DGGE), while the large exon 15 was examined using the protein truncation test.
      Using this approach, we identified 65 pathogenic mutations in the above 105
      apparently unrelated FAP families. The mutations were predominantly either
      frameshifts (39/65) or single base substitutions (18/65), resulting in premature
      stop codons. Mutations that would predict abnormal RNA splicing were identified
      in seven cases. In one of the families, a nonconservative amino acid change was
      found to segregate with the disease. In spite of the large number of APC
      mutations reported to date, we identified 27 novel germline mutations in our
      patients, which reiterates the great heterogeneity of the mutation spectrum in
      FAP. In addition to the point mutations identified in our patients, structural
      rearrangements of APC were found in two pedigrees, by Southern blot analysis. The
      present study indicates that the combined use of DGGE, protein truncation test,
      and Southern blot analysis offers an efficient strategy for the presymptomatic
      diagnosis of FAP by direct mutation detection. We found that the combined use of
      the currently available molecular approaches still fails to identify the
      underlying genetic defect in a significant subset of the FAP families. The
      possible causes for this limitation are discussed.

PMID- 8990003
TI  - Two extremes of the clinical spectrum of glycogen storage disease type II in one
      family: a matter of genotype.
AB  - Mutation analysis was performed in a nonconsanguineous Dutch caucasian family
      with a grandfather presenting the first symptoms of glycogen storage disease type
      II (acid alpha-glucosidase deficiency) in the sixth decade of life and a
      grandchild with onset of symptoms shortly after birth. The grandfather was
      identified as compound heterozygote having the IVS1(-13T-->G)/delta T525
      combination of mutant acid alpha-glucosidase alleles, the affected third
      generation offspring as homozygote delta T525/delta T525. The disease phenotypes
      in this family are in accordance with the genotypes since the IVS1(-13T-->G)
      mutation reduces acid alpha-glucosidase synthesis by 60 to 80%, whereas the delta
      T525 mutation completely prohibits the formation of catalytically active enzyme.
      Four additional families were identified with patients homozygote for delta T525
      and five others with an equally deleterious delta T525/delta exon 18 genotype.
      The nine latter patients had typically the infantile form of glycogen storage
      disease type II. The genotype-phenotype correlation is irrefutable.

PMID- 8990004
TI  - Mutations and polymorphisms in the tuberous sclerosis complex gene on chromosome
      16.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder of benign
      tumor formation, hamartomata, and hamartias. TSC has been shown to be genetically
      heterogeneous, with one causative gene mapping to chromosome 9q (denoted TSC1)
      and at least one other gene on chromosome 16p (denoted TSC2). The TSC2 gene was
      recently cloned. We have tested 88 TSC probands with the TSC2 cDNA by Southern
      blotting searching for gross deletions/rearrangements/insertions. We detected two
      deletions and a rare intragenic polymorphic variant. This is a similar rate of
      mutation detection (2/88; 2.3%) to that in the original report (10/260/; 3.8%).
      The rare polymorphic variant was initially detected in the proband of a
      chromosome 9-linked multiplex TSC family. The polymorphism segregated with
      previously tested markers on chromosome 16 independently of the disease gene,
      verifying that the variation was unrelated to TSC status. We have also begun
      searching for subtle mutations by SSCA and direct sequencing. After screening
      three exons, we found two intragenic polymorphic variants. Both polymorphisms are
      common, making them useful for linkage studies in known affected families.

PMID- 8990005
TI  - Identification of common polymorphisms in the coding sequence of the human MSH
      receptor (MCIR) with possible biological effects.
AB  - The extension locus has been identified in many mammalian species as a gene that
      determines the relative amounts of eumelanin and phaeomelanin pigments in hair
      and skin. In at least three species, this locus has been demonstrated to encode
      the melanocyte-stimulating hormone receptor (MC1-R), and functionally variant
      alleles have been demonstrated to cause a broad range of pigmentation phenotypes.
      To test for MC1-R allelic variation in man, genomic DNA was extracted from skin
      samples collected from patients with different skin types (I-VI), and eye and
      hair color. A PCR-based approach was used to amplify the full-length coding
      sequence of the MC1-R and the resulting products were sequenced. Two polymorphic
      alleles were identified with single point mutations in the coding sequence: a
      valine-to-methionine substitution at position 92 (V92M), and an aspartic acid-to
      glutamic acid substitution at position 84 (D84E). RFLP analysis demonstrated the
      presence of the V92M allele in 4 out of 60 (6.6%) of individuals examined,
      predominantly those with blue eyes and blond hair. This polymorphism was found in
      both heterozygous and homozygous states in individuals with type I skin. The D84E
      allele was found in one individual with skin type I; this person also has the V92
      M allele and thus is a compound heterozygote.

PMID- 8990006
TI  - A nonsense mutation due to a single base insertion in the 3'-coding region of
      glycogen debranching enzyme gene associated with a severe phenotype in a patient
      with glycogen storage disease type IIIa.
AB  - Glycogen storage disease type III (GSD-III) is an autosomal recessive disease
      resulting from deficient glycogen debranching enzyme (GDE) activity. A child with
      GDE deficient in both liver and muscle (GSD-IIIa) had recurrent hypoglycemia,
      seizures, severe cardiomegaly, and hepatomegaly and died at 4 years of age.
      Analysis of the GDE gene in this child by single-strand conformation
      polymorphism, followed by direct DNA sequencing and restriction analysis,
      revealed an insertion of a nucleotide A into position 4529 of the GDE cDNA
      (4529insA). This insertion resulted in substitution of a tyrosine to a stop codon
      at amino acid 1510 (Y1510X). The 4529insA mutation appeared to be homozygous in
      this patient and was not found in 20 unrelated controls or 18 other GSD-III
      patients (14 GSD-IIIa and 4 GSD-IIIb). This is the first identification of a
      disease mutation in this gene, and the data suggest that homozygous 4529insA may
      be associated with a severe phenotype in GSD-IIIa.

PMID- 8990007
TI  - Simultaneous genotyping for all three known structural mutations in the human
      mannose-binding lectin gene.
AB  - We describe a rapid and simple method for genotyping the three known structural
      mutations within exon 1 of the mannan-binding lectin (MBL) gene. A PCR
      amplifiable synthetic DNA (Universal Heteroduplex Generator) was annealed to
      genomic PCR product from exon 1 to generate unique DNA heteroduplexes for each
      mutation. Heteroduplexes were then resolved by non-denaturing polyacrylamide gel
      electrophoresis. The technique was initially validated with previously typed
      samples and then applied to previously untyped samples with the results confirmed
      by DNA sequencing.

PMID- 8990008
TI  - Mutation analysis of the connexin 32 (Cx32) gene in Charcot-Marie-Tooth
      neuropathy type 1: identification of five new mutations.

PMID- 8990009
TI  - Two new mutations in exon 3 of the NDP gene: S73X and S101F associated with
      severe and less severe ocular phenotype, respectively.

PMID- 8990010
TI  - Mutations of the androgen receptor gene in patients with complete androgen
      insensitivity.

PMID- 8990011
TI  - A glycine (415)-to-serine substitution results in impaired secretion and
      decreased thermal stability of type III procollagen in a patient with Ehlers
      Danlos syndrome type IV.

PMID- 8990013
TI  - Phenylketonuria in Spanish Gypsies: prevalence of the IVS10nt546 mutation on
      haplotype 34.

PMID- 8990012
TI  - A novel splice site mutation (156 + 1G-->A) in the TSC2 gene.

PMID- 8990014
TI  - A novel missense point mutation (S134N) of the Cu/Zn superoxide dismutase gene in
      a patient with familial motor neuron disease.

PMID- 8990015
TI  - Novel missense mutation in the coagulation factor IX catalytic domain associated
      with moderate disease.

PMID- 8990016
TI  - Novel mutation of the myelin P0 gene in a CMT1B family.

PMID- 8990017
TI  - Three novel mutations in the coproporphyrinogen oxidase gene.

PMID- 8990018
TI  - Two novel mutations (K384E and L539S) in the C-terminal moiety of the
      cystathionine beta-synthase protein in two French pyridoxine-responsive
      homocystinuria patients.

PMID- 8990019
TI  - Transthyretin ILE20, a new variant associated with late-onset cardiac
      amyloidosis.

PMID- 8990020
TI  - Probable identity by descent and discovery of familial relationships by means of
      a rare beta-thalassemia haplotype.

PMID- 8990021
TI  - Phenylketonuria splice mutation (EXON6nt-96A-->g) masquerading as missense
      mutation (Y204C).

PMID- 8990022
TI  - New splicing mutation in exon 5-6 of the p53-tumor suppressor gene in a malignant
      schwannoma.

PMID- 8990023
TI  - CTG trinucleotide repeat lengths in myotonic dystrophy alleles of patients with
      senile cataracts.

PMID- 8990024
TI  - Intraoperative monitoring of motor pathways during operative fixation of acute
      acetabular fractures.
AB  - OBJECTIVE: To determine whether intra-operative spontaneous electromyography
      (EMG) was superior to somatosensory evoked potentials (SSEP) in the prevention of
      iatrogenic sciatic nerve injury. DESIGN: Prospective, consecutive. SETTING:
      Tertiary referral, teaching Hospital in New York City. PATIENTS: Seventy-four
      patients with acutely displaced acetabular fractures. MAIN OUTCOME MEASURE: Group
      A consisted of 24 patients who underwent intraoperative sciatic nerve monitoring
      using SSEP only. Group B consisted of 50 patients who underwent monitoring using
      both SSEP and spontaneous EMG. Motor potentials were recorded from the tibialis
      anterior, peroneus longus, abductor hallucis, and flexor hallucis longus muscles.
      All patients had independent preoperative and postoperative evaluations by the
      same neurologist. RESULTS: One iatrogenic sciatic nerve injury occurred in group
      A and none in group B. Prolonged sciatic nerve compromise, demonstrated by
      significant intraoperative SSEP changes, occurred 2.4 times per case in group A
      and only 0.8 times per case in group B. In group B, spontaneous EMG noted
      compromise an average of 3.6 times per case (p < 0.0001). CONCLUSIONS: The
      results of this study support spontaneous EMG as feasible and superior to SSEP
      monitoring in detecting intraoperative sciatic nerve comprise in acute acetabular
      fracture surgery. Spontaneous EMG permits earlier detection of intraoperative
      sciatic nerve comprise, allowing a more rapid response of the surgical team to
      noxious nerve stimuli. This may prevent permanent neurologic sequellae.

PMID- 8990025
TI  - Pubic rami fracture: a benign pelvic injury?
AB  - OBJECTIVE: To present a consecutive series of older patients with pubic rami
      fractures and evaluate their long term functional outcome. STUDY DESIGN:
      Retrospective. METHODS: Sixty-three consecutive community-dwelling, ambulatory
      patients who sustained a public rami fracture and were treated at one hospital
      were reviewed. Fifty-two of sixty-three patients (83%) had radiographic evidence
      of pubic rami fracture at initial presentation; in the remaining eleven patients,
      the diagnosis of pubic rami fracture was made after additional imaging studies.
      Sixty patients (95%) required hospitalization for pain control and progressive
      mobilization. RESULTS: The hospital length of stay for the sixty admitted
      patients averaged fourteen days; patients who had three or more associated
      medical comorbidities or required use of a cane or walker for ambulation prior to
      fracture were more likely to have been hospitalized greater than two weeks.
      Thirty-eight patients were available for one year minimum follow-up; thirty-five
      of thirty-eight patients (92%) were living at home, 84% had no or mild complaints
      of hip/groin pain, 92% had returned to their prefracture ambulatory status, and
      95% had returned to their performance function in activities of daily living.
      CONCLUSIONS: 1) Elderly patients with pubic rami fractures utilize substantial
      healthcare resources based upon length of stay and need for home care services;
      and 2) those patients who survive have a good prognosis with regard to long term
      pain relief and functional outcome.

PMID- 8990026
TI  - Knee pain after tibial nailing.
AB  - OBJECTIVE: To determine the incidence and natural history of knee pain following
      tibial nailing. DESIGN: A retrospective analysis of patients treated by tibial
      nailing evaluating a consecutive series of patients with isolated tibial shaft
      fractures. SETTING: A level one trauma center in Vancouver, British Columbia.
      PATIENTS: A group of 107 consecutive patients with 110 tibial fractures treated
      by interlocking tibial nailing. INTERVENTION: Patients were contacted and
      interviewed by the authors. Clinical records and radiographs were analysed. MAIN
      OUTCOME MEASUREMENTS: Incidence of knee pain; time of onset; relationship of nail
      position on radiographs to knee pain; relationship to knee pain to site of nail
      insertion; response to nail removal. RESULTS: At a mean follow-up period of
      thirty-two months (12-58 months), sixty-one (57%) patients (63 of 110 knees) had
      developed anterior knee pain. There was no correlation between nail protrusion
      and knee pain. Insertion of the nail through the patella tendon was associated
      with a higher incidence of knee pain compared to the paratendon site of nail
      insertion (77% and 50% respectively). Of patients with knee pain, 80% (49/61)
      required nail removal. At a mean duration of 16 months following nail removal,
      pain was completely relieved in 22 patients and partially relieved in 17. In the
      remaining 10 patients, there was no improvement. CONCLUSIONS: Based on this data,
      we would recommend a parapatellar tendon incision for nail insertion, and nail
      removal for those patients with a painful knee. The causes of knee pain after
      tibial nailing are multi-factorial and require further study.

PMID- 8990027
TI  - Strength recovery in fractured sheep tibia treated with a plate or an internal
      fixator: an experimental study with a two-year follow-up.
AB  - OBJECTIVES: Comparison of fracture healing with two different implants: a
      conventional Dynamic Compression Plate (DCP) and a new internal Point Contact
      Fixator (PC-Fix). DESIGN: Randomized, prospective study in experimental animals.
      Observation times: 12, 24, 48 and 96 weeks, with six sheep per group. SETTING:
      Following surgery, animals were kept with unrestricted weight-bearing in
      individual stalls for 12 weeks, thereafter in groups. ANIMALS: 56 adult Swiss
      mountain sheep. INTERVENTION: A standardized oblique fracture of the sheep tibia
      was reduced and compressed by a lag screw and "neutralized" with one of the
      implants. MAIN OUTCOME MEASUREMENTS: Standard radiographs were used for callus
      size measurements. After sacrifice the implant was removed and both the treated
      bone and the contralateral bone were tested for static strength in bending with
      the plate side under tension. Broken bones were processed for histological
      evaluation. RESULTS: In the DCP group all six bones failed through the original
      fracture at 12 weeks. At 24 and 48 weeks two out of six, at 96 weeks one out of
      six bones failed through the original fracture, others through one of the screw
      holes. In the PC-Fix group there were no failures through the original fracture
      with a single exception at 96 weeks. The strength values in the PC-Fix groups of
      12 and 96 weeks were significantly higher then in the corresponding DCP groups.
      CONCLUSIONS: Healing of simple diaphysial fractures treated by PC-Fix was
      superior to that achieved by conventional plating. The histological evaluation
      suggested that the observed differences can be accounted for by the absence of
      implant-related cortical necrosis and by the circumferentially uninterrupted (if
      smaller) callus in the PC-Fix group.

PMID- 8990028
TI  - Compartment pressures during nonreamed tibial nailing without traction.
AB  - OBJECTIVE: To assess the intracompartmental pressure changes during the nailing
      of acute tibia fractures with the extrinsic factors of 90 degrees/90 degrees
      positioning, posterior thigh posts, continuous traction, and remaining removed.
      STUDY DESIGN: Prospective case control. METHODS: Fifty-eight acute tibia
      fractures were nailed using an unreamed technique without leg elevation, thigh
      post, or continuous traction. Two presented with compartment syndrome and had
      fasciotomy before nailing. Thirty of the remaining fifty-six tibias had
      continuous intracompartmental pressure monitoring of the anterior compartment.
      RESULTS: The highest pressures were routinely seen during manual reduction of the
      fracture (20-58mms Hg; avg = 34mm Hg) and during nail passage (15-56mms Hg; avg =
      26mms Hg). In fifteen tibias, the pressure rose to within 30mmg Hg of the
      diastolic pressure and in 12 tibias the pressure exceeded 40mmg Hg. The pressures
      in all cases returned to baseline immediately following nail passage (avg =
      13.8mms Hg). No sequelae of compartment syndrome was found in any of the 56
      tibias presenting without compartment syndrome. There were no iatrogenic
      compartment syndromes in the series. CONCLUSION: When extrinsic factors that
      increase intramedullary pressures are avoided, then intramedullary nailing raises
      the intramedullary pressure only momentarily. The pressure peaks during manual
      reduction and nail passage, and then returns to normal before the patient is
      awakened. Intramedullary nailing performed without reaming or traction is safe
      with respect to compartment syndromes and continuous pressure is not required.

PMID- 8990030
TI  - Intraarticular calcaneus fractures: a biomechanical comparison or two fixation
      methods.
AB  - OBJECTIVE: To compare the strength of fixation obtained using two unicortical 4.0
      mm diameter cancellous screws versus two bicortical 3.5 mm diameter cortical
      screws in the fixation of intra-articular calcaneus fractures. DESIGN: In eight
      paired fresh frozen cadaver feet, the subtalar joint complex, consisting of the
      talus, interosseous ligaments, and calcaneus was removed as a unit. An oblique
      osteotomy of the calcaneus was then created in the sagittal plane. The two
      fragments were reduced and stabilized using either two unicortical 4.0 mm
      diameter cancellous screws or two bicortical 3.5 mm diameter cortical screws. A
      force was then applied to the medial calcaneal tuberosity until failure occurred.
      In all specimens testing was discontinued due to ligamentous failure, without
      causing bony disruption. RESULTS: In all specimens the forced applied to the
      calcaneus created a disruption of the interosseous ligaments across the subtalar
      joint and rotation of the calcaneus on the talus. Thus in each specimen, testing
      was discontinued due to interosseous ligamentous failure, without causing bony
      disruption. There was no statistically significant difference in force to failure
      between the specimens fixed with 3.5 mm diameter cortical screws as compared to
      those fixed with 4.0 mm diameter cancellous screws. CONCLUSIONS: The lack of a
      statistically significant difference in force to failure of the intra-articular
      calcaneus fractures fixed using 3.5 mm diameter cortical screws as compared to
      those fixed using 4.0 mm diameter cancellous screws and, the fact that the mode
      of failure was a disruption of ligaments rather than bony disruption suggest that
      either method of screw fixation is biomechanically adequate.

PMID- 8990029
TI  - A new technique for complex fibula fracture fixation in the elderly: a clinical
      and biomechanical evaluation.
AB  - OBJECTIVE: To determine whether intramedullary fixation could augment plate
      fixation strength in comminuted and osteopenic fibula fractures. STUDY DESIGN:
      Retrospective clinical study and biomechanical laboratory study. METHODS: Twenty
      comminuted or osteopenic fibula fractures in twenty patients age fifty years or
      older were stabilized using plate fixation augmented with intramedullary
      Kirschner wires. Nineteen patients were available for follow-up which averaged
      15.4 months (range, 6-43 months). In conjunction with this clinical series, a
      biomechanical evaluation was performed comparing fixation of mildly osteopenic
      fibulas using this technique to plate and screws alone. The fibulas were first
      tested non destructively in bending, and then destructively in torsion to
      determine stability and ultimate strength of the fixation. RESULTS: All nineteen
      fractures united without loss of reduction: seventeen of nineteen patients (89%)
      had either no pain, slight or mild pain. Biomechanical testing demonstrated that
      the resistance to bending of the plated fibulas augmented with Kirschner wires
      was 81% greater than the fibulas stabilized with a plate alone (p < .05). In
      torsional testing, the augmented group had twice the resistance to motion than
      the plate group (p < .002). CONCLUSION: This clinical series and biomechanical
      study support the use of plate fixation augmented with intramedullary Kirschner
      wires for the treatment of comminuted and osteopenic fibula fractures in the
      elderly.

PMID- 8990031
TI  - Irreducible open intertrochanteric hip fracture secondary to entrapment of the
      sciatic nerve in a child.

PMID- 8990032
TI  - Femoral nerve palsy associated with an associated posterior wall transverse
      acetabular fracture.
AB  - A case is presented of a patient who sustained bilateral acetabular fractures in
      a motor vehicle crash. On the right, he sustained a variant associated posterior
      wall transverse fracture, with a femoral nerve lesion noted preoperatively. Open
      reduction and internal fixation of both fractures was performed in a staged
      fashion with an ilio-inguinal approach on the right. At surgery, the femoral
      nerve was 90% divided and damaged over approximately 5 cm of length, with marked
      damage also of the ilio-psoas muscle and tendon and the inguinal canal. No
      attempt was made to repair the nerve, and at 11-month follow-up he has had no
      recovery and electrodiagnostic tests indicate no femoral nerve function.

PMID- 8990033
TI  - Reimplantation of the totally extruded talus.
AB  - We present two cases of traumatic total extrusion of the talus, leaving no soft
      tissue attachment. The management of this rare injury is controversial. These
      cases were managed by reimplantation of the tali. The tali revascularised and
      survived without collapse. One patient developed posttraumatic osteoarthritis of
      the ankle.

PMID- 8990034
TI  - Open total talus dislocation: case report and review of the literature.
AB  - An open pure total lateral dislocation of the right talus with extrusion of the
      whole talar body is reported. Immediately surgical debridement, reduction, and
      primary closure were accomplished under antibiotic coverage. The ankle was
      immobilized for 6 weeks, and weight-bearing was restricted for 6 more weeks.
      Neither avascular necrosis (AVN) of the talus nor infection developed. Both ankle
      and foot regained full pain-free range of motion at 16 weeks, except for a mild
      restriction of the last 5 degrees of supination. Four years postinjury, the
      patient continues in the same preinjury occupation. A thorough review of the
      literature suggested that (a) immediate closed or open reduction is preferable;
      (b) if AVN develops, it can be treated in most cases by weight-bearing
      restrictions; and (c) talectomy, alone or associated with a tibiocalcaneal
      arthrodesis, should be reserved for an eventual reconstructive procedure,
      particularly in the event of talus infection.

PMID- 8990035
TI  - Nonunion of distal radial fractures associated with distal ulnar shaft fractures:
      a report of four cases.
AB  - Although complications following distal radial fractures are common, nonunion is
      rare. We report four cases of radial nonunion following distal radial fractures
      that occurred in elderly women after low-energy falls. The distinctive feature of
      these injuries was the presence of an associated distal ulnar shaft fracture. All
      patients had initial closed reduction and cast immobilization, which was
      unsuccessful. Reconstruction was complicated by deformity, disuse osteoporosis,
      radiocarpal stiffness, and distal radioulnar joint disruption. Wrist arthrodesis
      improved function and decreased pain and deformity in three patients. Metaphyseal
      distal radial fractures associated with distal ulnar shaft fractures represent an
      unstable injury pattern, and closed reduction and casting may not be adequate
      treatment. Once established nonunion is present, wrist arthrodesis is a useful
      salvage procedure.

PMID- 8990036
TI  - A simple technique for creating hybrid fixators using a modified AO single
      adjustable clamp.
AB  - Hybrid external fixators with limited internal fixation have become popular in
      the treatment of complex intraarticular fractures of the tibia. A wide variety of
      hybrid external fixation systems are commercially available, but these frames are
      expensive and not always readily available. The authors present a simple hybrid
      frame constructed from the AO tubular and Ilizarov type external fixator sets
      using a modified AO single adjustable clamp. This hybrid frame is easy to apply,
      versatile, and significantly less expensive than other commercially available
      adaptors and frames.

PMID- 8990037
TI  - Subfascial plate fixation of comminuted diaphyseal femoral fractures: a report of
      three cases utilizing biological osteosynthesis.
AB  - Internal fixation with preservation of tissues and vascularization, as in
      intramedullary fixation and bridging plate osteosynthesis, so-called biological
      osteosynthesis, has become increasingly popular. Our experiences, in three
      patients, using a technique of internal fixation of comminuted diaphyseal femoral
      fractures with an AO plate in subfascial position without exposure of the
      fracture site is presented. Though based on unorthodox mechanical principles, the
      safety and efficacy of bridging plates, even when applied in unusual situations,
      are illustrated.

PMID- 8990038
TI  - Avulsion fracture of the calcaneus: report of a case using a new tension band
      technique.
AB  - We report a case of avulsion fracture of the calcaneus in an 83-year-old woman.
      Nonoperative treatment was not considered satisfactory. However, the os calcis
      was osteoporotic, and internal fixation therefore was performed with a transverse
      Kirschner pin through the os calcis, securing a figure-of-8 metal tension band
      wiring to the fragment. We suggest that this technique provides a strong internal
      fixation in selected cases.

PMID- 8990039
TI  - Planning the design phase of a clinical study.

PMID- 8990040
TI  - The school of nurse as health educator.
AB  - Contrary to common opinion, the number of nurses who provide services in the
      nation's preschool, elementary, and secondary schools is not declining and
      currently is about 30,000. These members of school health teams can play a
      variety of roles that have a positive impact on patterns of health behaviors
      established during school years. Contributions that school nurses can make to
      school health instruction could include teaching individual clients, providing
      classroom instruction, being a member of curriculum planning committees, sharing
      resources with classroom teachers, and modeling health-promoting behavior.
      Although all school nurses should assume roles in health education, this article
      provides a framework to help nurses make decisions about which roles are
      appropriate in their practice setting, which tasks are within their area of
      expertise, and how health education fits into expectations of their employers.
      Specific roles in staff health promotion that use the unique experience,
      knowledge base, and skills of nurses are suggested, as well as ways that nurses
      can be advocates for comprehensive school health education. The article also
      poses four questions to assist nurses in evaluating their situation and their
      ability to be effective providers and advocates of health education in school.

PMID- 8990041
TI  - Guidelines for school health programs to promote lifelong healthy eating.
AB  - Healthy eating patterns in childhood and adolescence promote optimal childhood
      health, growth, and intellectual development; prevent immediate health problems,
      such as iron deficiency anemia, obesity, eating disorders, and dental caries; and
      may prevent long-term health problems, such as coronary heart disease, cancer,
      and stroke. School health programs can help children and adolescents attain full
      educational potential and good health by providing them with the skills, social
      support, and environmental reinforcement they need to adopt long-term, healthy
      eating behaviors. This report summarizes strategies most likely to be effective
      in promoting healthy eating among school-age youths and provides nutrition
      education guidelines for a comprehensive school health program. These guidelines
      are based on a review of research, theory, and current practice, and they were
      developed by CDC in collaboration with experts from universities and from
      national, federal, and voluntary agencies. The guidelines include recommendations
      on seven aspects of a school-based program to promote healthy eating: school
      policy on nutrition, a sequential, coordinated curriculum, appropriate
      instruction for students, integration of school food service and nutrition
      education, staff training, family and community involvement, and program
      evaluation.

PMID- 8990042
TI  - The relationship between peer, social, and school factors, and delinquency among
      youth.
AB  - This article examines the relationships between self-reported delinquency and
      peer, social, and school factors among junior and senior high school students in
      Calgary, Alberta, Canada, using both cross-tabulation and multiple-regression
      analyses. A greater number of ninth grade students were delinquent compared to
      students in the other grades studied. Predictably, peers' level of delinquency
      correlated strongly and positively with students' level of delinquency. Strong,
      positive correlations with delinquency also were found for students reporting
      high levels of involvement in sports, and high levels of involvement in
      commercial/entertainment activities. Multivariate analyses indicated the
      strongest predictor of delinquent behavior within the group of peer and social
      variables was peer delinquency. Within the group of school variables, the
      strongest predictors of delinquent behavior were how often classes were skipped
      and the number of times students were suspended from school. However, students'
      grades in school did not significantly increase the accuracy of the regression
      equation.

PMID- 8990043
TI  - Hypotonicity-activated efflux of taurine and myo-inositol in rat inner medullary
      collecting duct cells: evidence for a major common pathway.
AB  - To further characterize the hypotonicity-activated efflux pathways for the
      organic osmolytes taurine and myo-inositol in inner medullary collecting duct
      (IMCD) cells tracer fluxes of taurine and myo-inositol were investigated. The
      time course of activation of both fluxes after exposure of cells isolated at 600
      mosm to a hypotonic medium (300 mosm by omission of sucrose) was identical with a
      major increase of release within the first 10 min. All 'anion channel blockers'
      employed proved to be strong inhibitors of both fluxes. Inhibition of myo
      inositol efflux by 0.5 mM NPPB and 0.1 mM dideoxyforskolin was not significantly
      different from that of taurine efflux (87.7 +/- 11.4 compared to 94.6 +/- 4.6%
      and 98.8 +/- 2.0 compared to 95.9 +/- 3.7%). However, SITS (0.5 and 0.01 mM),
      DIDS (0.5 and 0.01 mM), and niflumic acid (0.5 mM) inhibited myo-inositol efflux
      more strongly than taurine efflux. The respective values were 65.4 +/- 4 vs. 42.9
      +/- 3.6% for 0.01 mM SITS, 65.7 +/- 4.2 vs. 45.8 +/- 2.0% for 0.01 mM DIDS, and
      79.5 +/- 3.5 vs. 54.2 +/- 2.5% for 0.5 mM niflumic acid. Taurine as well as myo
      inositol efflux were decreased to a similar extent by 10 mM extracellular ATP
      (26.9 +/- 6.3 vs. 29.8 +/- 17.7% inhibition), by 10 mM extracellular cAMP (52.8
      +/- 9.8 vs. 60.1 +/- 17.2% inhibition) and by reduction of the intracellular ATP
      content employing 2-deoxy-D-glucose (31.9 +/- 5.9 vs. 40.4 +/- 13.6% inhibition).
      In polarized primary cell cultures taurine and myo-inositol were released during
      a hypotonic shock primarily across the basal-lateral membrane, the ratio of
      basolateral versus apical efflux was 4.1 for taurine and 3.9 for myo-inositol.
      Apical fluxes were more sensitive to 0.01 mM SITS or DIDS; this was particularly
      evident for apical myo-inositol efflux which was inhibited by 0.01 mM SITS by
      84.1 +/- 5.9% compared to 43.5 +/- 13.1% inhibition of the basolateral efflux.
      Thus, taurine and myo-inositol efflux show to a great extent a similar cellular
      distribution, intracellular regulation and pharmacological inhibition profile.
      This similarity suggests that the two osmolytes share an efflux pathway that
      might be identical with the swelling-activated taurine conductance described
      previously. Additional minor pathways can, however, not be excluded.

PMID- 8990044
TI  - 1,25-dihydroxyvitamin D3 and the synthetic vitamin D analogue, KH 1060, modulate
      the growth of mouse proximal tubular cells.
AB  - Apart from its classical role in bone and mineral metabolism, 1,25
      dihydroxyvitamin D3 (1,25-vitamin D3) has recently been shown to affect cell
      growth and differentiation from a variety of tissues primarily not involved in
      mineral metabolism and to provide immunomodulatory functions. Findings in human
      mesangial cells in vitro as well as in rat model of compensatory renal growth in
      vivo suggest that renal cells are a target for 1,25-vitamin D3. In the present
      study the effects of 1,25-vitamin D3 and a synthetic vitamin D analogue, KH 1060,
      on proliferation and protein synthesis were investigated in a mouse proximal
      tubular cell line (MCT). 1,25-vitamin D3 and KH 1060 inhibited cell proliferation
      dose dependently (10(-7) to 10(-12) M) and specifically as assessed by 3H
      thymidine incorporation (DNA synthesis) and cell counting. The cellular protein
      concentration, protein synthesis (3H-methionine incorporation) and protein/DNA
      ratio were not influenced by 1,25-vitamin D3 and KH 1060. By analyzing c-fos and
      c-myc expression using semiquantitative RT-PCR, a constant basal expression of
      both protooncogenes, even under serum-free conditions, was found in MCT cells.
      Phorbol 12-myristate 13-acetate (TPA) further stimulated c-fos and c-myc
      expression, whereas treatment with 1,25-vitamin D3 (10(-7) M) it had no effect
      either in unstimulated or in TPA-stimulated cells. In conclusion, 1,25-vitamin D3
      and a synthetic vitamin D analogue, KH 1060, provide growth-regulating effects on
      renal proximal tubular cells in vitro. These effects are not mediated by
      regulation of c-fos and c-myc. Further studies will have to clarify whether 1,25
      vitamin D3 plays a physiologic role in renal development and growth in vivo.

PMID- 8990045
TI  - Effect of renal ischemia on organic anion and cation transport in rabbit proximal
      tubule.
AB  - The uptake of organic anion, p-aminohippurate (PAH), and organic cation,
      tetraethylammonium (TEA), was measured in cortical slices and plasma membrane
      vesicles isolated from the proximal tubule of ischemic rabbit kidneys. The uptake
      of PAH or TEA in cortical slices increased after 30 or 60 min of ischemia. When
      the kidneys were reperfused for 30 min, the uptake of organic ions returned to
      control levels. When ischemic (60 min) slices were preincubated for 120 min in an
      oxygenated medium, the stimulatory effect of ischemia on organic ion uptake was
      not observed. The PAH uptake by basolateral membrane vesicles and brush border
      membrane vesicles (BBMV) was not altered following 60 min of ischemia. However,
      the TEA uptake by BBMV but not basolateral membrane vesicles was significantly
      reduced. The dissipation rate of H+ gradient across the BBMV was similar in
      control and ischemic kidneys. The Vmax for TEA transport in BBMV isolated from
      ischemic kidneys was significantly reduced, but the Km was not altered. These
      results indicate that the organic cation secretory system is more vulnerable to
      ischemia than the organic anion secretory system in the rabbit renal proximal
      tubule.

PMID- 8990046
TI  - Effects of nitric oxide inhibition on systemic and renal hemodynamics in the
      hemorrhaged rat.
AB  - The systemic and renal hemodynamic responses to nitric oxide (NO) inhibition with
      L-Name were compared in both normotensive, normovolemic rats and in rats
      following acute hemorrhagic hypotension. The mean arterial blood pressure
      increased in normovolemic as well as in hemorrhaged, hypotensive rats. The
      systemic vascular resistance also increased in both groups, but the increase was
      greater in normotensive rats (104 +/- 11%) than in hypotensive rats (64 +/- 14%).
      The renal vascular resistance also increased more in normotensive rats (189 +/-
      20%) than in hypotensive rats (102 +/- 19%; p < 0.05). The glomerular filtration
      rate was markedly reduced by L-Name in normovolemic rats (from 3.0 +/- 0.1 to 2.1
      +/- 0.1 ml/min/300 g), but increased in hemorrhaged rats following L-Name (from
      1.8 +/- 0.2 to 2.5 +/- 0.2 ml/min/300 g). In summary, the L-Name-induced increase
      in vascular resistance is markedly reduced following hemorrhage, suggesting that
      NO production or availability is reduced. However, the NO production continues in
      the hemorrhaged rat and contributes substantially to the hypotension and
      functional renal insufficiency associated with acute severe volume depletion.

PMID- 8990047
TI  - Platelet mitochondrial respiratory chain function in Parkinson's disease.
AB  - Reports on mitochondrial respiratory chain (MRC) complex I (CI) dysfunction in
      the substantia nigra in Parkinson's disease (PD) support the oxidative stress
      hypothesis in the neuropathogenesis of PD. Studies in peripheral tissue have
      found variable decreased CI and occasionally other complex activity suggestive of
      systemic impairment of MRC function in PD; however, MRC activity may be
      influenced by numerous variables. We conducted spectrophotometric measurements of
      MRC function in platelet mitochondrial preparations in 13 individuals with PD and
      9 age-matched controls (CON) and have identified additional variables that may
      affect MRC activity. Mean CI, CIII, CIV, and citrate synthase (CS) activities
      were similar between PD and CON. CIII and CIV, specific and CS-corrected,
      activities were significantly positively correlated with CI in combined and
      individual group data, with the exception of CIII CS-corrected and CIV specific
      activities in CON and PD, respectively. CIII and CS specific activities were
      negatively correlated with age in CON, but varied randomly in PD. In PD, CIII
      specific activity was 1.4-fold higher in those with a history of environmental
      risk factors for PD and CIV specific activity was lower in those with a positive
      family history of PD [8.34 +/- 0.74 (n = 4) vs. 12.4 +/- 1.1 (SEM) min-1 mg-1; p
      = 0.046]. Group heterogeneity, variables affecting enzyme activity, and intrinsic
      properties of cells may thus contribute to conflicting data in studies of MRC
      function in platelets and other tissues.

PMID- 8990048
TI  - Defects of cytochrome c oxidase in the substantia nigra of Parkinson's disease:
      and immunohistochemical and morphometric study.
AB  - Defects of respiratory chain complexes were considered as possible pathogenetic
      mechanisms in Parkinson's disease (PD). Changes of cytochrome c oxidase (COX) in
      four different nuclei of the substantia nigra of 8 PD cases and 10 age-matched
      controls were investigated by means of morphometry and immunohistochemistry.
      Pigmented neurons with COX defects were randomly distributed within the the four
      nuclei of PD cases, but only in the posterolateral nucleus was the numerical
      density of pigmented neurons with COX defects significantly increased compared
      with controls. The numerical density of pigmented neurons without COX defects was
      significantly reduced in the anteromedial, anterointermediolateral, and
      posterolateral nuclei in PD. The cell size of pigmented neurons with and without
      COX defects was significantly diminished in the anteromedial and posterolateral
      nuclei of PD cases. It is suggested that complex IV defects in nigral neurons are
      most probably a result of accelerated aging, but are least likely to be a primary
      aspect of the pathogenetic processes occurring in PD.

PMID- 8990049
TI  - Levodopa induces apoptosis in cultured neuronal cells--a possible accelerator of
      nigrostriatal degeneration in Parkinson's disease?
AB  - Apoptosis is an active, intrinsic cell suicide program. We recently suggested
      that it may have a role in the death of nigrostriatal dopaminergic neurons in
      Parkinson's disease (PD). We now report that levodopa, the current major therapy
      for PD, is a potent inducer of apoptosis in cultured postmitotic chick
      sympathetic neurons. Levodopa, in a concentration range of 0.01-0.3 mM, caused
      the characteristic apoptotic cascade of cell shrinkage, massive membrane
      blebbing, and nuclear fragmentation, as evident by nuclear flow cytometry and
      fluorescence microscopy. Levodopa-induced apoptosis was inhibited by
      antioxidants, indicating that it may be mediated by autooxidation-reactive
      species. Levodopa treatment for PD may therefore constitute an additional
      challenge for the defective apoptosis-inhibiting systems in the nigrostriatal
      neurons. Despite reassuring data from some, but not all, previous studies, these
      findings suggest that the possible in vivo toxic effects of levodopa on the
      survival of the remaining nigral neurons should be further explored.

PMID- 8990050
TI  - Measurement of rigidity in Parkinson's disease.
AB  - Clinical assessment of rigidity in parkinsonian patients is largely qualitative.
      The reliability and validity of the assessments are sometimes in doubt. Several
      "engineering" methods of quantifying rigidity have been described, but none has
      been adopted into general clinical practice. A possible reason is that these
      methods differ in crucial aspects from the clinical exam. We therefore tackled
      the problem by monitoring the clinical exam itself, using small sensors to
      measure the forces and displacements applied. Limb impedance (Z) was computed
      using parameter identification methods and compared to raters' verbalized ratings
      of rigidity based on a 5-point scale: the Unified Parkinson's Disease Rating
      System. The qualitative and quantitative estimates of impedance covaried over a
      fourfold range, depending on the forces imposed and the subject's motor set.
      Raters differed by up to 1 full point in their mean qualitative ratings and
      sometimes disagreed on whether levodopa reduced rigidity. This was not due to any
      significant differences in the overall range of rigidity they evoked, but rather
      to the way they scored this range [the ratio of mean rating to mean impedance
      (R/Z) varied between raters and subjects]. On the other hand, the R/Z ratio was
      reproducible over separate sets of ratings and may therefore serve to convert
      measured impedance into a standardized rating. Our results indicate that the
      current clinical exam may be too abbreviated to detect the sometimes quite small
      reductions in rigidity after levodopa. We conclude that a device that
      conveniently quantifies the clinical assessment of rigidity is now available and
      will lead to more standardized protocols for rating rigidity in the near future.

PMID- 8990051
TI  - Long-term changes of striatal dopamine D2 receptors in patients with Parkinson's
      disease: a study with positron emission tomography and [11C]raclopride.
AB  - We used [11C]raclopride (RACLO) and positron emission tomography (PET) to study
      longitudinally striatal dopamine D2 receptor binding in nine patients with
      Parkinson's disease (PD) at an early drug-naive stage and 3-5 years later, when
      motor fluctuations had appeared in seven of them. Patients were treated with a
      combination of levodopa and dopamine agonists. Data were compared with 10 healthy
      controls in the same age range. Initially, patients with PD showed a significant
      increase of RACLO uptake in the putamen compared with controls (p < 0.04). The
      caudate nucleus revealed values in the normal range. After 3-5 years, RACLO
      binding was significantly reduced in the putamen (p < 0.03) and caudate nucleus
      (p < 0.03) compared with baseline. Values were now in the control range in the
      putamen and reduced in the caudate nucleus (p < 0.05). The clinical score at
      "off" had significantly worsened (p < 0.0005) compared with the first PET scan.
      The nine PD patients reported here had already been investigated 3-4 months after
      therapy began and that time did not show a reduction of the initially increased
      RACLO binding capacity (data published previously). These results indicate long
      term downregulation of striatal dopamine D2 receptor binding in PD. Receptor
      changes in the striatum of patients with PD may be induced by chronic
      dopaminergic therapy or occur independently of treatment, as a result of
      structural adaptation of the postsynaptic dopaminergic system to the progressive
      decline of nigrostriatal neurons.

PMID- 8990053
TI  - The characterization and outcome of stereotypical movements in nonautistic
      children.
AB  - Stereotypies are patterned, repetitive, purposeless movements that are performed
      the same way each time. They are commonly seen in individuals with autism,
      schizophrenia, or mental retardation, and also occur as a feature of tardive
      dyskinesia and as movements in those with akathisia. We studied 10 children who
      had stereotypies but were not autistic or mentally retarded. Although most had an
      uneventful delivery, seven had mild to moderately delayed developmental
      milestones. Five had hyperactive behavior or attention-deficit problems. All
      appeared to be of normal intelligence. The median age of onset of stereotypies
      was 12 months. The stereotypies including arm flapping, arm and hand posturing,
      finger wiggling, body rocking, leg shaking, facial grimacing, involuntary noises,
      neck extension, and eye blinking. Of the 10 children, only two stopped having
      stereotypies eventually without medications.

PMID- 8990052
TI  - The neurological syndrome of infantile cobalamin deficiency: developmental
      regression and involuntary movements.
AB  - Developmental regression is the presenting symptom of most infants with cobalamin
      (Vitamin B12) deficiency. We present a report of three infants with cobalamin
      deficiency in which the infants also developed a movement disorder. In each case
      the mother was a vegetarian and the infant was exclusively breast-fed. In two of
      the infants, a striking movement disorder consisting of a combination of tremor
      and myoclonus particularly involving face, tongue, and pharynx appeared 48 h
      after the initiation of treatment with intramuscular cobalamin. This was
      associated with marked changes in plasma amino acid levels. Paradoxically, the
      onset of the movement disorder coincided with overall neurological improvement.
      The third infant had a persistent focal tremor, which appeared before the
      commencement of treatment. The movements slowly abated during a 3-6 week period.
      The presence of a movement disorder in cobalamin deficiency has received less
      attention than other features, but in a mild form is probably common. It may
      offer an early clue to the diagnosis before the onset of profound neurological
      deterioration. The cause of the severe movement disorder that can appear after
      treatment is not known.

PMID- 8990054
TI  - Movement disorders in adult hydrocephalus.
AB  - In a prospective series of symptomatic adult hydrocephalus characterized by gait
      disturbance, cognitive impairment, and/or urinary incontinence, 88 of 118
      patients (75%) had additional akinetic, tremulous, hypertonic, or hyperkinetic
      movement disorders. Their prevalence was highest in patients with idiopathic
      normal pressure hydrocephalus (NPH) of the elderly (56/65 patients, 86%), and
      they were less frequent in patients with secondary NPH (10/15, 66%), with
      nonhydrodynamic atrophic/other hydrocephalus (20/33, 61%), and with obstructive
      hydrocephalus/aqueductal stenosis (2/5, 40%). Akinetic symptoms were found in 73
      of 118 patients (62%), and the most frequent movement disorder was upper
      extremity bradykinesia (55%). Akinetic, tremulous, hypertonic, and hyperkinetic
      movement disorders were exclusively secondary to causes not related to
      hydrocephalus in 24 of 118 patients (20%). The proportion of patients with
      movement disorders not attributable to only such causes was highest in the
      idiopathic NPH group (44/65, 68%). Thirteen of 118 patients (11%) presented with
      a parkinsonian syndrome. There was evidence for coexistent Parkinson's disease in
      four of these patients. Parkinsonism was found to be secondary to NPH in five
      patients and was found improved after shunting. Akinetic symptoms in patients
      with NPH generally responded favorably to CSF diversion, which was evident in 80%
      of a subset of this group. Various other movement disorders did not show definite
      improvement. The high prevalence of bradykinesia and other akinetic symptoms in
      NPH and the beneficial effect of shunting on such symptoms suggest that NPH may
      cause a more generalized disorder of motor function.

PMID- 8990055
TI  - Clinical, polysomnographic, and genetic characteristics of restless legs
      syndrome: a study of 133 patients diagnosed with new standard criteria.
AB  - One hundred thirty-three cases of restless legs syndrome (RLS), diagnosed with
      criteria recently formulated by an international study group, were studied by
      questionnaire and with all-night polysomnographic recordings. Results show that
      RLS starts at a mean age of 27.2 years and before age 20 in 38.3% of patients.
      Symptoms often appear in one leg only and also involve upper limbs in about half
      of all cases. Most patients (94%) report sleep-onset insomnia or numerous
      nocturnal awakenings due to RLS symptoms. A strong relationship was found between
      these complaints and polysomnographic findings; increasing sleep latency and
      number of awakenings and decreasing sleep efficiency were associated with
      worsening symptoms. Periodic leg movements in sleep (index > 5 movements/h sleep)
      were found in 80.2% of patients. This study shows that this percentage is
      increased when 2 recording nights are considered (most severe score). Eighty
      patients of 127 (63%) reported the presence of RLS in at least one of their first
      degree relatives. In these families, 221 of 568 first-degree relatives (39%) were
      reported by the patients to be affected with RLS.

PMID- 8990056
TI  - Propriospinal myoclonus upon relaxation and drowsiness: a cause of severe
      insomnia.
AB  - Three patients, aged 71, 50, and 41 years, presented with myoclonic activity
      arising in the relaxation period preceding sleep onset and causing severe
      insomnia. Polygraphic studies showed that the myoclonic activity began in
      spinally innervated muscles, propagating at low speed to rostral and caudal
      muscular segments. Myoclonus arose whenever patients relaxed mentally and showed
      diffuse electroencephalographic alpha activity and was independent of posture.
      The jerks disappeared during sleep. Clonazepam afforded symptomatic improvement.
      Propriospinal myoclonus arising from a spinal generator may be facilitated by
      changes in supraspinal control related to vigilance levels. When arising during
      relaxation and drowsiness, it may cause severe insomnia.

PMID- 8990057
TI  - The effect of catecholamine precursor L-dopa on sleep bruxism: a controlled
      clinical trial.
AB  - The putative role of the dopaminergic system in sleep bruxism (SB) was studied in
      a double-blind clinical trial by using low doses of short-term L-dopa in
      combination with benserazide. We recorded 10 patients with SB in our sleep
      laboratory for 3 consecutive nights. The first night was for habituation to the
      laboratory environment. During the second and the third nights, the patients
      received two doses of either L-dopa or a placebo in a crossover fashion: the
      first dose 1 h before bedtime and the second, 4 h after the first one. The order
      of administration was reversed in half the patients. The efficacy of L-dopa was
      analyzed by using multilevel models. L-Dopa resulted in a significant decrease in
      the average number of bruxism episodes per hour of sleep, as well as in a
      significant reduction in the average value of the root-mean-square (RMS)
      electromyography (EMG) level per bruxism burst. This indicates that L-dopa exerts
      an attenuating effect on SB. In addition, L-dopa caused a reduction in the
      variance in RMS values, which suggests that L-dopa normalizes the EMG activity
      patterns associated with SB.

PMID- 8990058
TI  - Comparison of transcranial sonography, magnetic resonance imaging, and single
      photon emission computed tomography findings in idiopathic spasmodic torticollis.
AB  - Various lines of evidence suggest that the basal ganglia and thalamus are
      involved in the pathogenesis of idiopathic dystonia, but unfortunately
      neuroradiological and pathological data are sparse and controversial. In this
      study, we have examined 10 patients with spasmodic torticollis by neuroimaging
      techniques, including transcranial sonography (TS; n = 10), conventional (n = 10)
      and diffusion-weighted (n = 5) magnetic resonance imaging (MRI), and single
      photon emission computed tomography (SPECT; n = 10), employing
      [123I]iodobenzamide (IBZM) as a ligand with a high affinity to the D2 receptor.
      In seven patients, TS showed small hyperechogenic lesions in the medial segments
      of the lentiform nucleus contralateral to the side of head deviation. In
      accordance with the site of TS abnormalities, diffusion-weighted MRI displayed a
      hyperintense lesion in only one patient, while standard MRI of this area was
      normal in all patients. SPECT revealed a slight but statistically nonsignificant
      reduction of IBZM tracer uptake in an area corresponding to the dorsal portions
      of the striatum in 9 of the 10 patients. TS findings support the hypothesis that
      structural alternations of the pallidothalamic circuit contralateral to the side
      of head deviation are involved in the pathogenesis of idiopathic spasmodic
      torticollis. TS may be more sensitive in detecting basal ganglia alterations than
      MRI.

PMID- 8990060
TI  - The EBD test--a clinical test for the detection of antibodies to botulinum toxin
      type A.
AB  - Approximately 5 to 10% of patients with cervical, segmental or multifocal
      dystonia receiving repetitive local injections with botulinum toxin A (BTX A) are
      estimated to develop secondary loss of treatment benefit (nonresponding) because
      of the formation of circulating serum antibodies against the neurotoxin. Because
      other reasons may account for loss of benefit during the course of treatment, the
      group of secondary nonresponders because of antibody formation need to be
      separated from the antibody-negative group by appropriate testing. We present an
      easy clinical antibody test based on a test injection of BTX A into an indicator
      muscle, the extensor digitorum brevis (EDB), combined with amplitude measurements
      of compound muscle action potentials (CMAPs) elicited by electrical nerve
      stimulation of the peroneal nerve before and after the injection. The results
      show that in a group of clinically defined secondary nonresponders, who were
      serologically proven to be antibody negative, a marked decrease in CMAP amplitude
      can consistently be detected in the injected EDB 4 weeks after BTX A injection.
      In contrast, antibody-positive patients are characterized by a lack of such
      decrease in amplitude. In all cases, results of the EDB test were in keeping with
      the standard mouse bioassay test. We conclude that the EDB test is a useful tool
      for clinicians faced with the question of whether a secondary nonresponding
      patient has in fact developed antibodies to BTX A.

PMID- 8990059
TI  - The variability in the clinical effect induced by botulinum toxin type A: the
      role of muscle activity in humans.
AB  - When botulinum toxin (BT) is administered for the first time at fixed doses,
      variable clinical responses can be observed in patients with the same form of
      dystonic disorder. Many factors may contribute to this phenomenon, including the
      variability rate of absorption of the drug. Animal experimental models (rat
      diaphragm preparation) have demonstrated an increased absorption of BT in the
      terminal nerve endings of the muscle under repetitive electrical stimulation,
      suggesting that "muscle activity" also may play an important role. The aim of our
      study was to evaluate in humans the role of the muscle activity on the
      variability of the effect induced by BT type A. Eleven patients with
      blepharospasm and idiopathic facial hemispasm were studied by using
      neurophysiologic techniques. In nine patients, both extensor digitorum brevis
      (EDB) muscles were injected with low (3 IU), fixed doses of type A BT. For the
      first 24 h after administration of the drug, periodic electrical stimulation of
      only one EDB was used. The subsequent percentage changes in compound muscle
      action potential (CMAP) amplitude was calculated at different intervals over a 30
      day period. The percentage in the CMAP for the stimulated EDB was compared with
      that of the contralateral nonstimulated side. We found that the effect of the
      induced neuromuscular blockade was significantly greater for the stimulated side.
      In the other two patients, we injected BT in one EDB and the same volume of
      normal saline solution in the contralateral muscle to assess the stability of the
      CMAP in untreated muscle over time. We observed that the CMAP was unchanged in
      the untreated EDB; therefore we concluded that muscle activity plays an important
      role in the variability of clinical response often seen.

PMID- 8990061
TI  - Comparison of clinical rating scales in treatment of cervical dystonia with
      botulinum toxin.
AB  - Seventy-six consecutive patients with cervical dystonia. (CD) treated with
      botulinum toxin were assessed with the Tsui rating scale, the Toronto Western
      Spasmodic Torticollis Rating Scale (TWSTRS), and a global scale of improvement.
      Tsui, TWSTRS, and TWSTRS subscale scores all showed significant improvement. Tsui
      and TWSTRS score reduction rates correlated significantly with each other, and
      each correlated with the global scale. Analysis of these scales and TWSTRS
      subscales indicates that an objective scale of severity such as either the Tsui
      rating scale or TWSTRS severity subscale used in conjunction with the TWSTRS pain
      subscale adequately assesses improvement of CD following treatment with botulinum
      toxin.

PMID- 8990062
TI  - Short-term levodopa test assessed by movement time accurately predicts
      dopaminergic responsiveness in Parkinson's disease.
AB  - Short-term challenges with dopaminergic agents are used in patients with
      idiopathic Parkinson's disease (PD) to predict the therapeutic effect of
      sustained levodopa treatment, but false-negative results often occur. We
      prospectively evaluated 74 patients with clinically diagnosed IPD and compared
      the predictive value of a short-term levodopa test assessed by movement time (MT)
      with the predictive value obtained by the evaluation with the motor examination
      part of the Unified Parkinson's Disease Rating Scale (UPDRS-ME). The response to
      long-term levodopa was accurately predicted in 96% of patients by assessing the
      response to the short-term test with MT and in 80% of cases with UPDRS-ME.
      Similar predictive values were obtained by separately analyzing 21 de novo
      patients. The short-term test also accurately predicted the magnitude of
      improvement with long-term treatment. We conclude that the predictive value for
      long-term dopaminergic responsiveness may be further enhanced by evaluating the
      short-term pharmacologic challenges with MT analysis. This is particularly useful
      to select de novo patients for drug trials with dopaminergic agents.

PMID- 8990063
TI  - A long-term follow-up study of cinnarizine- and flunarizine-induced parkinsonism.
AB  - The natural course of calcium-entry blocker-induced parkinsonism was evaluated in
      13 elderly patients previously exposed to cinnarizine or flunarizine or both for
      a median period of 7 months. Clinical assessments were carried out before drug
      discontinuation and twice thereafter over a period lasting < or = 7 years. None
      of the patients showed a full recovery of extrapyramidal signs, indicating that
      the long-term prognosis of the parkinsonism is less benign than previously
      reported. Two main patterns of clinical outcome were recognized (i.e.,
      "remittent" and "persistent and not progressive" parkinsonism), whereas the
      development of a progressive disorder was observed only in one patient. No
      significant correlation was found between the patterns of outcome and some
      clinical variables, such as total duration of exposure to cinnarizine and
      flunarizine, cumulative drug dosages, and age at onset of parkinsonism. There was
      no significant difference in terms of family history of essential tremor or
      parkinsonism or both among patients with the two main patterns of clinical
      course.

PMID- 8990064
TI  - Ophthalmoplegia and leg myorhythmia in Whipple's disease: report of a case.
AB  - Whipple's disease (WD) is a rare disorder that is more common in males than in
      females. Progressive supranuclear ophthalmoplegia (SNO) in conjunction with
      oculomasticatory myorhythmia (OMM) or oculofacioskeletal myorhythmia are
      characteristic movement abnormalities when WD involves the nervous system. Limb
      myorhythmia without facial or ocular myorhythmia has not been reported in WD. We
      report such a case who had SNO and leg myorhythmia but no facial or ocular
      myorhythmia. She had onset of WD at age 28 and 16 years later developed SNO and
      leg myorhythmia. The neurological manifestations did not respond to antimicrobial
      agents or to the drugs used for parkinsonism or essential tremor. Valproate
      produced a remarkable improvement in leg myorhythmia, but the efficacy declined
      after 3 months. Because WD may infest as a neurological disorder without
      gastrointestinal symptoms, all SNO cases, with or without OMM, and those with
      skeletal myorhythmia should be suspected of WD. These patients should be treated
      vigorously and followed carefully since neurological involvement is the most
      disabling feature and it has a propensity to relapse.

PMID- 8990065
TI  - Cerebellar presentation of multiple system atrophy.
AB  - Early diagnosis of multiple-system atrophy (MSA) is important in patients
      presenting with late-onset cerebellar ataxia because it has a less favourable
      prognosis than other degenerative ataxic disorders. We report cerebellar
      presentation of MSA in a series of 16 patients, 3 of whom later developed
      parkinsonism. Two-thirds of them had early evidence of impaired postural reflexes
      with a history of recurrent falls. Some of these had a narrow-based, unsteady
      gait, unlike the more classic broad-based gait ataxia of cerebellar disease. On
      review of the patients' histories, genitourinary dysfunction (particularly
      impotence) was present at the onset of, or preceding, cerebellar ataxia in 60% of
      patients, but this had often been attributed to age, or to urological or
      gynaecological causes. External striated anal or urethral sphincter
      electromyography (EMG) demonstrated features of chronic denervation and
      reinnervation in 14 (93%) of 15 patients, consistent with degeneration in Onuf's
      nucleus as occurs in MSA. Autonomic function tests were abnormal in 9 (64%) of 14
      patients. Our data suggest that close enquiry into genitourinary function and
      analysis of the gait disorder can be useful pointers to a diagnosis of MSA in
      patients with an unexplained adult-onset progressive cerebellar syndrome, and
      that sphincter EMG is the most useful investigation in this context.

PMID- 8990066
TI  - Viewpoint: reductionism and the study of neurodegenerative disorders.

PMID- 8990067
TI  - Risperidone-induced tardive dyskinesia and parkinsonism.

PMID- 8990068
TI  - Primary Sjogren's syndrome presenting as progressive parkinsonian syndrome.

PMID- 8990069
TI  - Improvement of parkinsonian signs after vascular lesions of the basal ganglia
      circuitry.

PMID- 8990070
TI  - Essential myoclonus and myoclonic dystonia.

PMID- 8990071
TI  - Timed tests in Parkinson's disease evaluation.

PMID- 8990072
TI  - Birthdates of the tyrosine hydroxylase immunoreactive neurons in the hypothalamus
      of male and female rats.
AB  - This study determined the birthdates of the tyrosine hydroxylase-(TH)
      immunoreactive (IR) neurons in the zona incerta (ZI), periventricular nucleus
      (PeVN) and arcuate nucleus (AN) of male and female rats. 'Long-survival'
      [3H]thymidine autoradiography combined with TH immunocytochemistry, the first
      enzyme of catecholamine synthesis, was used. In males, TH-IR neurons originate in
      the ZI between embryonic days (E) 12 and 13, while in the PeVN and AN this
      process is prolonged until E16. The majority of TH-IR neurons became postmitotic
      at E12 in the ZI, between E12 and E14 in the PeVN and at E15 in the AN. The
      birthdate of TH-IR neurons was sexually dimorphic with (a) generation of the
      majority of TH-IR neurons in the ZI in males proceeding that in females, (b)
      generation of TH-IR neurons in the AN of males delayed as compared to females,
      and (c) average daily fractions of the newborn TH-IR neurons in each hypothalamic
      region of females exceeding that seen in males. This sexual dimorphism was
      observed prior to E16, i.e. before the onset of sex difference in androgen
      levels, implying a hormone-independent mechanism, determined at the genetic
      level.

PMID- 8990073
TI  - Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid
      receptor gene expression and elevates blood pressure in the adult offspring in
      the rat.
AB  - Human epidemiological data show a strong association between low birth weight and
      hypertension in adulthood, an effect that has been ascribed to 'fetal
      programming'. In rats fetoplacental exposure to maternally administered
      dexamethasone throughout gestation reduces birth weight and produces hypertensive
      adult offspring, though the mechanism is unclear. Pre- and postnatal stress
      programmes hypothalamic-pituitary-adrenal (HPA) axis responses throughout the
      lifespan, an effect thought to be mediated via permanent effects on
      glucocorticoid receptor (GR) and/or mineralocorticoid receptor (MR) gene
      expression in the hippocampus. Corticosteroids also have specific central effects
      on blood pressure control mediated by GR and MR. This study investigated
      corticosterone (CORT) responses to restraint stress and GR and MR gene expression
      in areas of the brain postulated to mediate the central effects of
      corticosteroids on (i) HPA axis suppression (hippocampus), and (ii) blood
      pressure (organ vasculosum of the lamina terminalis (OVLT), sub-commissural
      organ, area postrema and nucleus tractus solitarius). Pregnant Wistar rats
      received dexamethasone (100 micrograms/kg.day-1) or vehicle on days 15-20 of
      gestation. This reduced birth weight by 11%. When the offspring were 16 weeks
      old, blood pressure was recorded directly and plasma CORT measured basally (AM)
      and after 30 min restraint. GR and MR mRNA expression were determined by in situ
      hybridization. Blood pressure was significantly elevated in the adult offspring
      of dexamethasone-treated pregnancies (dexamethasone 144 +/- 2/125 +/- 2 mm Hg vs.
      control 133 +/- 2.7/112 +/- 2.8 mm Hg; both p < 0.01). Offspring of dexamethasone
      treated pregnancies had increased basal plasma CORT (155 +/- 29 nmol/l) compared
      to offspring of controls (79 +/-15 nmol/l, p < 0.05), but the CORT response to
      stress was similar. Hippocampal neuronal GR mRNA expression was significantly
      lower in the offspring of dexamethasone-treated pregnancies (dentate gyrus 20%
      lower, CA1 15% lower; p < 0.01). Similarly, hippocampal MR gene expression was
      decreased in CA1 and CA2 by 24 and 25%, respectively (p < 0.05). No differences
      in GR or MR mRNA expression were found in the OVLT, subcommissural organ, area
      postrema or nucleus tractus solitarius. These findings suggest that
      glucocorticoid excess in the last trimester of rat pregnancy (i) is sufficient to
      programme offspring hypertension; (ii) also increases basal plasma CORT levels,
      and (iii) permanently attenuates GR and MR mRNA expression in specific
      hippocampal subfields. Thus, if translated into protein, may reduce sensitivity
      to glucocorticoid feedback and thus contribute to the CORT excess. However,
      hypertension in this model is unlikely to be mediated by similar changes in GR or
      MR gene expression in the examined areas of the brain putatively involved in the
      more direct central regulation of blood pressure.

PMID- 8990074
TI  - Differential mechanisms of ovine fetal pituitary stimulation by a selective kappa
      opioid agonist and by dynorphin.
AB  - Dynorphin has long been considered the putative endogenous ligand for the kappa
      opioid receptor. The high density of kappa-opioid receptors in the hypothalamus
      and the high concentration of dynorphin peptides in the pituitary suggest that
      they may play an important role in regulation of the hypothalamic-pituitary
      adrenal (HPA) axis. To investigate this possibility in early development, we
      examined the effects of a highly selective kappa-opioid agonist, U50488H (trans-
      (+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide) and
      dynorphin A1-13 on plasma immunoreactive adrenocorticotropin (ir-ACTH) in the
      ovine fetus. Although both U50488H (1.0 mg/kg i.v.) and dynorphin A1-13 (0.5
      mg/kg i.v.) evoked a similar robust increase in ir-ACTH levels, the response to
      dynorphin A1-13 peaked at 15 min while the maximal response to U50488H was not
      seen until 60 min following administration. In addition, the response to
      dynorphin A1-13, but not U50488H, was dependent upon the gestational age of the
      fetus. The response to U50488H was blocked by naloxone as well as antagonists of
      AVP and CRF indicating that U50488H is eliciting its effects via opioid
      receptors, most likely of the kappa receptor subtype, at the hypothalamus.
      Conversely, the dynorphin A1-13 response was not blocked by any of the
      aforementioned antagonist. Thus, it appears that dynorphin A1-13 may act as a
      direct mediator of ACTH release via nonopioid receptors at the level of the
      pituitary.

PMID- 8990075
TI  - Intracerebral administration of mineralocorticoid receptor antisense
      oligonucleotides attenuate adrenal steroid-induced salt appetite in rats.
AB  - The amygdala contains mineralocorticoid (MR) and glucocorticoid receptors (GR)
      involved in the arousal of salt appetite. In the present investigation, MR
      antisense oligonucleotides injected into the amygdala inhibited salt appetite
      induced by systemic desoxycorticosterone (DOCA) but not adrenalectomy (ADX). In
      contrast, GR antisense or scrambled oligonucleotides had no effect on stimulated
      salt intake. MR antisense oligomers also decreased MR but not GR in amygdala,
      whereas GR antisense oligomers decreased GR but not MR. Immunocytochemical
      labelling of the biotinylated MR antisense revealed that distribution of the
      oligomer was restricted to the injection site, with incorporation in neurons and
      neighboring glial cells. Together, these data demonstrate the utility of receptor
      antisense oligonucleotides for investigating the central actions of adrenal
      steroids and the role of amygdala in MR in DOCA-induced sodium intake.

PMID- 8990076
TI  - Effect of stress on mouse and rat brain metallothionein I and III mRNA levels.
AB  - The effect of immobilization stress on brain and liver metallothionein (MT) mRNA
      levels has been studied in mice and rats. Stress increased brain and liver MT-I
      mRNA levels in mice in a time-dependent manner, in agreement with the MT-I+II
      protein levels, suggesting an increased gene transcription during stress. In
      contrast, the brain-specific isoform, MT-III, tended to decrease during stress.
      In selected brain areas of rats, the overall tendency for both MT-I and MT-III
      mRNA levels was to be transiently decreased by stress in hippocampus, and
      increased in hypothalamus, cerebellum and the remaining brain tissues;
      adrenalectomy significantly affected MT mRNA levels either in basal conditions or
      during stress, with very different temporal patterns of response depending on the
      brain area studied. These results suggest that glucocorticoids could be involved
      in MT-I but also MT-III regulation. In both rats and mice, the subtle response to
      stress observed in the brain contrasts with the robust response in the liver,
      suggesting that the factors involved in MT regulation in both tissues differ
      substantially. In primary cultures enriched in astrocytes or neurons, MT-III mRNA
      was clearly detected by Northern blotting in both cases, suggesting that it is
      expressed in both types of cells. Dexamethasone appeared to decrease MT-III mRNA
      levels in cultured neurons and to increase them in astrocytes, which indicates
      that glucocorticoids have a different role in MT-III regulation in both cell
      types.

PMID- 8990077
TI  - Age and gender influence basal and stress-modulated hypothalamic-pituitary
      thyroidal function in Fischer 344/N rats.
AB  - To investigate possible gender- and age-associated changes of the hypothalamic
      pituitary-thyroid (HPT) axis at baseline and during stress, we studied healthy
      young (3-month) and old (23-month) female 344/N Fischer rats at the basal state
      and after 2 h of immobilization (IMMO), in parallel to age-matched male rats. At
      baseline, there were no major differences on HPT axis functions between young
      female and male animals. Old age was associated with impaired central thyroid
      function in both genders, albeit to a much lesser extent in females than in
      males. Plasma prolactin (PRL) levels were similar in young females and males but
      were higher in old females than males. IMMO inhibited HPT axis functions in both
      genders in young, but not old animals. Thus, plasma TSH and hypothalamic TRH mRNA
      levels were decreased by IMMO in young, but not in old rats of both genders. IMMO
      increased plasma PRL in young and old males, but did not have any effect in young
      and old females. In summary, these data indicate that age and gender exert
      diverse effects on HPT axis functions at baseline and after stress.

PMID- 8990078
TI  - Evidence for a physiological role for nitric oxide in the regulation of the LH
      surge: effect of central administration of antisense oligonucleotides to nitric
      oxide synthase.
AB  - Antisense oligonucleotides of brain-nitric oxide synthase (b-NOS) and endothelial
      NOS (e-NOS) were used in steroid-primed ovariectomized rats to examine the
      physiological role of nitric oxide in the regulation of the LH surge. Since
      macrophage-NOS (m-NOS) is not produced in the hypothalamus under normal
      conditions, the m-NOS antisense oligonucleotide was used as control for the
      possible toxicity of the phosphorothioated and propynylated antisense
      oligonucleotides used. Female rats were ovariectomized on day 70 of age and
      implanted with a third ventricle cannula on day 77 of age, injected with 5
      micrograms of estradiol on days 84 and 85 of age at 17.00 h and with 1 mg
      progesterone or vehicle on day 86 at 09.00 h. Blood samples were collected
      between 13.00 and 19.00 h on day 86 of age via a jugular cannula inserted on day
      85 of age. Antisense oligonucleotides (400 or 800 ng) or vehicle were injected in
      the third ventricle at 17.00 h on days 84 and 85 just before the estradiol
      injection and at 06.00 and 12.00 h on day 86. Neither the 400-ng nor the 800-ng
      dose of m-NOS AS had any effect on the steroid-induced LH surge. In contrast,
      central administration of the 400-ng dose of e-NOS AS and the 800-ng dose of b
      NOS AS significantly attenuated the steroid-induced LH surge. The 40% reduction
      in LH by e-NOS AS and b-NOS AS was accompanied by a 33 and 28% reduction in their
      respective protein levels as shown by Western blots. The higher amount of b-NOS
      AS needed to reduce the LH surge is probably due to the high abundance of b-NOS
      in the hypothalamus as compared to e-NOS. As a whole, this study provides
      significant evidence for a physiological role of nitric oxide in mediating the
      steroid-induced LH surge.

PMID- 8990079
TI  - GnRH-stimulated glycosylation (proximal and distal) of luteinizing hormone by
      cultured rat pituitary cells.
AB  - In the present work, the effects of GnRH on the translation (by [14C]leucine
      incorporation; [14C]Leu-LH) and the glycosylation of LH by rat pituitary cells in
      primary culture were established. The use of specific markers as radioactive
      precursors made it possible to discriminate the action of the neurohormone on
      proximal glycosylation (by[3H]mannose incorporation; [3H]Man-LH) as well as
      distal glycosylation (by [3H]galactose incorporation; [3H]Gal-LH) in the course
      of synthesis and release of LH. Pituitary cells from ovariectomized adult rats
      were incubated for different periods between 0 and 5 h in medium containing
      [14C]Leu plus [3H]Man or [14C]Leu plus [3H]Gal with or without 10 nM GnRH. GnRH
      increased synthesis and release of newly synthesized LH. The magnitude of the
      stimulatory effect on the kinetics of [14C]Leu (slope = 63.58; 158% of control)
      and [3H]Man (slope = 75.15; 161%) incorporation to LH was similar. The action of
      the neurohormone appears to be exerted on translation, the increased [3H]Man
      incorporation being a secondary phenomenon arising from the greater amount of
      available polypeptide chains as acceptors of the polymannose core. However, a
      direct effect of GnRH on proximal glycosylation cannot be excluded. GnRH also
      stimulated the kinetics of release of [14C]Leu-LH (slope = 6.14; 236% of control)
      and [3H]Man-LH (slope = 8.06; 191%). Comparatively, the effect of GnRH on [3H]Gal
      LH was detected earlier than that on LH labeled with the other precursors;
      increases in rates of production (slope = 71.57; 278% of control) and release
      (slope = 32.08; 494%) were higher than those in [14C]Leu- and [3H]Man-LH
      kinetics, indicating that GnRH acts specifically on this distal step of LH
      glycosylation. GnRH enhanced the relative terminal glycosylation
      ([3H]Gal/[14C]Leu ratio) of total and release LH without modifying the relative
      proximal glycosylation ([3H]Man/[14C]Leu ration) of the hormone. We conclude that
      GnRH can induce not only changes in the quantity (greater number of molecules)
      but also in the quality (molecules more glycosylated) of the secreted LH by
      acting directly at translation and distal glycosylation level.

PMID- 8990080
TI  - Exposure to a short photoperiod increases sensitivity to dopamine inhibition of
      prolactin release from Siberian hamster pituitary.
AB  - Prolactin (PRL) secretion from the anterior pituitary is tonically controlled by
      the activity of the hypothalamic tuberoinfundibular dopaminergic (TIDA) system.
      Changes in TIDA activity have been associated with the decrease in basal PRL
      levels shown by hamsters exposed to a short-day photoperiod. Potential concurrent
      changes in the sensitivity of pituitary lactotropes to the inhibitory actions of
      dopamine on PRL release were investigated in tissue harvested from animals that
      had been preexposed to either a stimulatory, long-day 16-hour-light:8-hour-dark
      (16L:8D) photoperiod, or to a nonstimulatory, short-day (10L:14D) photoperiod for
      8-10 weeks. Tissue was maintained in a perifusion tissue culture system and
      received a 1-hour pulse of varying concentrations of dopamine (DA) shortly after
      the equilibration period. Fractions of the media were collected every 1/2 h and
      PRL concentrations in each sample determined via radioimmunoassay. At the highest
      concentration of DA (10(-6) M), a highly significant inhibition of PRL levels was
      seen for both 16L and 10L pituitaries. At both mid range concentrations of DA
      (10(-7) and 10(-8) M), both tissue types showed a significant suppression of PRL,
      but the reduction was greater for tissue that had been obtained from 10L animals.
      At the lowest concentration of DA (10(-9) M), a significant suppression of PRL
      occurred for tissue harvested from 10L animals, but not for tissue taken from 16L
      animals. These results indicate that the responsiveness of anterior pituitary
      tissue to the inhibitory effects of DA are altered by photoperiod exposure, and
      this change is likely a consequence of changes in the characteristics of the D2
      receptor population on pituitary lactotropes. Short-day-induced increases in
      sensitivity to the inhibitory effects of DA may be due to increases in receptor
      number, or to increased affinity of the D2 receptor for its ligand.

PMID- 8990081
TI  - Reversal of sex roles in genetic female mice by disruption of estrogen receptor
      gene.
AB  - Deficiency of normal estrogen receptor(ER) gene function led to behavioral change
      in female mice (ERKO females). Maternal behavior as measured by retrieving of
      pups was reduced. In some cases, pups were killed by the ERKO females, which was
      not seen in wild-type animals. Aggression toward other females was increased.
      Female-typical lordosis behavior was reduced for at least two reasons: less
      response to somatosensory stimuli on the hindquarters, as well as the fact that
      ERKO females were immediately treated as intruder males by resident 'stud' males
      and were thus attacked. In sum, disruption of the ER gene led to a pattern of
      hormonal and neural changes which caused the females to lose their normal female
      typical behavior and to behave and be treated more like males.

PMID- 8990082
TI  - The existence of antibodies specific for DNA in systemic autoimmune diseases.

PMID- 8990083
TI  - Monoclonal anti-DNA antibodies: structure, specificity, and biology.
AB  - Anti-DNA antibodies are a major contributor to the pathogenesis associated with
      the autoimmune disease systemic lupus erythematosus in mice and human. The
      accumulation of a large body of structural information on autoimmune anti-DNA
      antibodies over the past several years, particularly from mice, has provided
      considerable insight into the structure, function, and biology of this important
      class of autoantibodies. Even though the germline repertoire of light and heavy
      chain variable regions that may encode DNA-specific antibodies is very large in
      mice, there are individual light and heavy chain variable region genes that have
      been recurrent and preferentially expressed among anti-DNA hybridomas. This has
      been particularly true for hybridomas producing antibodies that bind duplex, B
      form, mammalian DNA (dsDNA). Recurrent somatically derived variable region
      structures, particularly arginines in the third complementary-determining region
      of the heavy chain (VH-CDR3), have also been recurrent and preferentially
      expressed among monoclonal anti-DNA antibodies. In fact specificity for dsDNA can
      be correlated to the relative amino acid position at which arginines are
      expressed within VH-CDR3 of anti-DNA. Most important from the results of
      structural analyses of monoclonal anti-DNA autoantibodies has been the
      realization that autoimmunity to DNA results from a clonally selective, antigen
      specific immune response to DNA. Autoimmune antibodies to DNA have all of the
      characteristics of secondary immune antibodies. In further support of this
      hypothesis, we have been able to induce anti-DNA antibodies in normal,
      nonautoimmune mice by immunization with immunogenic DNA-peptide complexes. The
      induced antibodies have all of the structural and functional characteristics of
      autoimmune anti-DNA including the pathogenetic potential to induce
      glomerulonephritis. This review summarizes the results of research from our
      laboratory that support the above conclusions.

PMID- 8990084
TI  - Bacterial expression of anti-DNA antibody domains.
AB  - Bacterial production of recombinant Fab or Fv domains of antibodies is an
      important tool for analyzing structural correlates of antigen binding or idiotype
      expression. Bacterial products may be Fab or Fv molecules that assemble from
      separate chains in the periplasm or a single-chain Fv protein. This article
      describes properties and applications of a plasmid vector used for production of
      single-chain Fv (scFv). The expression cassette, initially designed for
      production of the Fv domain of anti-Z-DNA mAb Z22, has a bacterial secretion
      signal that permits secretion of soluble scFv into growth medium. A single B
      domain of staphylococcal protein A facilitates affinity purification and generic
      assay of products independent of antigen-binding activity. Gene segment swapping
      and directed mutagenesis identified structural features important for Z-DNA
      binding and revealed the structural similarity of autoantibody and immunization
      induced antibody. The H and L regions of mAb Z22 are readily replaced by those of
      any cloned Ig, a library of V regions, or other proteins. Modified forms of the
      vector code for production of separate H or L chain V regions, which can
      associate with each other to form functional Fv complexes. Although there is
      large variation in the yield with different V regions, most clones provide enough
      soluble product for antigen-binding assays. Current developments are aimed at
      increasing the yield consistency to allow production of enough material for three
      dimensional structural analysis.

PMID- 8990086
TI  - The structure of human lupus anti-DNA antibodies.
AB  - B-cell hyperactivity and production of pathogenic autoantibodies are the main
      immunological events in the pathogenesis of the human autoimmune disease systemic
      lupus erythematosus. One approach to studying the pathogenesis of this disease
      and to understanding how the autoantibody response is initiated and sustained has
      been to analyze the variable genes expressed by antibodies that have the
      hallmarks of the disease-causing subset of pathogenic autoantibodies. Such
      studies have provided important clues. Quantitation of this repertoire revealed
      the presence of a specific expansion of IgG clonotypes that impart reactivity
      with disease-related autoantigens. The sequences of the genes encoding
      autoantibodies derived from these patients and expressing nephritogenic idiotopes
      (present in immune complexes and renal eluates of subjects with active disease)
      show features of molecular diversification with a high rate of replacement/silent
      mutations and clustering of the mutations in the hypervariable regions. These
      characteristics imply that a pure polyclonal B-cell activation process cannot be
      the only mechanism responsible for autoantibody production. More likely, an
      antigen drive plays a role in generation of pathogenic autoantibodies. Based on
      additional studies of their light chain variable region genes, we have offered a
      novel genetically based model whereby B cells secreting pathogenic lupus
      autoantibodies are blocked in their capacity to turn off their autoreactivity and
      to acquire a new specificity, a mechanism called receptor editing. Studies of the
      molecular events involved in this mechanism and of the clonal fates of B cells in
      vivo will be important for future research.

PMID- 8990085
TI  - Selection of recurrent V genes and somatic mutations in autoantibodies to DNA.
AB  - Antigen selection of autoantibodies to DNA results in the use of limited sets of
      immunoglobulin heavy and light chains, characteristic VDJ and VJ joining regions,
      and recurrent patterns of somatic mutations. In the past, we have used site
      directed mutagenesis to examine the roles of two recurrent features of anti-DNA
      antibodies: VHCDR3 arginine and somatic mutations to arginine. We observed that
      in one prototypic anti-DNA antibody, 3H9, a suitable CDR3 conformation is
      essential for DNA binding and depends on arginine. In addition, arginines at any
      of five positions in CDR1, CDR2, or FWR3 of the heavy chain contribute contacts
      with the antigen. Here, we extend these studies and report that arginines at
      positions 52 and 58 improve relative DNA binding but that binding critically
      depends on the germline-encoded arginine at position 50. These observations
      provide a more detailed view of the anti-DNA combining site and suggest that
      structural features account, at least in part, for the recurrence of heavy chain
      variable regions in anti-DNA antibodies.

PMID- 8990087
TI  - Autoantibodies to nucleosomes and histone-DNA complexes.
AB  - Individuals with systemic autoimmune diseases develop autoantibodies to
      nucleosome antigens. For many years, investigators have devoted much effort to
      precisely mapping epitopes on individual chromatin components. This approach,
      however, overlooks the existence of determinants that result from multimolecular
      interactions among nucleosome elements, such as DNA and histones. Anti-nucleosome
      antibodies can recognize a variety of complex epitopes and are especially
      prevalent in spontaneous and drug-induced lupus. Using numerous monoclonal anti
      nucleosome antibodies obtained from autoimmune mice, we have further
      characterized these determinants and sequenced the variable region genes of these
      autoantibodies. I herein review these studies and their implications for the
      origin of antinuclear autoantibodies.

PMID- 8990088
TI  - Human polyomavirus BK and immunogenicity of mammalian DNA: a conceptual
      framework.
AB  - Although the origin of autoimmune antibodies to double-stranded DNA (dsDNA) is
      not known, the variable-region structures of such antibodies indicate that they
      are produced in response to antigen-selective stimulation. In accordance with
      this, results from experiments using artificial complexes of DNA and DNA-binding
      polypeptides for immunizations have indicated that DNA may induce these
      antibodies. The immunogenicity of DNA in vivo may therefore depend upon
      structures, or processes, that render DNA immunogenic. It is therefore crucial to
      determine the nature of the antigen(s) recognized by anti-DNA antibody-inducing
      Th cells. We describe here the results of a series of experiments using
      polyomavirus BK (BKV) inoculation as a model system for initiation of antibodies
      to DNA, including dsDNA, in animals. From the early observation that BKV had the
      potential to induce the linked production of antibodies to DNA and histones, we
      have investigated and described the molecular bases for how this virus may do so.
      The minimum requirement for DNA to act as an immunogen is the in vivo expression
      of the BKV early gene encoding the DNA-binding large T-antigen. In the context of
      in vivo expression of this gene, IgG antibodies to dsDNA, histones, and T-antigen
      were produced. Monoclonal anti-dsDNA antibodies derived from BKV immunized mice
      demonstrated variable-region structures highly similar to those of spontaneous
      anti-DNA antibodies in murine lupus. These results represent a conceptual advance
      in understanding a potential molecular basis for initiation of autoimmunity in
      systemic lupus erythematosus and establish a precedent for further studies on
      polyomavirus expression as one biological origin for anti-dsDNA antibodies in
      human lupus.

PMID- 8990089
TI  - Specificity and immunochemical properties of antibodies to bacterial DNA.
AB  - DNA is a structurally heterogeneous molecule that elicits antibody production in
      both normal and aberrant immunity. In the prototypic autoimmune disease systemic
      lupus erythematosus, anti-DNA antibodies occur prominently and are serological
      markers for diagnosis and prognosis. These antibodies target conserved sites on
      both single-stranded (ss) and double-stranded (ds) DNA from essentially all
      species. In contrast, sera of normal human subjects (NHS) contain antibodies that
      selectively bind to DNA from certain bacteria. The NHS antibodies differ from
      lupus anti-DNA in their exclusive binding to foreign DNA as well as in their
      isotype, light chain distribution, and mode of DNA interaction. The properties of
      these antibodies suggest that they arise as a specific response to bacterial DNA
      introduced during infection or colonization. This conclusion is supported by
      studies demonstrating that bacterial DNA is a potent immunogen in normal mice and
      can induce antibodies specific for determinants on bacterial ss and dsDNA.
      Furthermore, immunization of normal animals with bacterial DNA elicits antibodies
      that bind mammalian as well as bacterial ssDNA; this immunization can also
      provoke glomerulonephritis. In addition to its immunogenicity, bacterial DNA is
      mitogenic, stimulating polyclonal activation of murine B cells; bacterial DNA can
      also induce cytokine production in the mouse. The range of immunological
      activities of bacterial DNA suggests an important role of this molecule in
      stimulating host defense in normal individuals and provoking autoimmunity in
      individuals predisposed to SLE.

PMID- 8990090
TI  - Structural features of nephritogenic lupus autoantibodies.
AB  - We have identified monoclonal antibodies derived from MRL-lpr/lpr lupus-prone
      mice that produced nephritis after passive transfer to normal mice. Our present
      goal was to elucidate the structural and immunochemical features of nephritogenic
      Ig that facilitate immune deposition. For this purpose the antigen binding
      properties, capacity to form immune deposits, and nucleotide sequence of a
      genetically related autoantibody subgroup were compared. The prototype, H147 (an
      IgG encoded by 7183/81X VH gene), produced glomerular and tubular basement
      membrane, mesangial immune deposits, and proliferative glomerulonephritis after
      passive transfer to normal mice. For comparison three other 7183/81X encoded anti
      DNA IgG (H257, H171, and H8a) were evaluated (predicted heavy chain aa homology
      >75%). H257 produced similar types of immune deposits as H147, and this was
      associated with nephritis; H8a produced predominantly mesangial deposits, whereas
      H171 did not produce significant deposits. Although their antigen binding profile
      to a panel of soluble autoantigens was variable, only H147 and H257 bound to both
      mesangial and aortic endothelial cell surfaces. V gene sequence analysis of the
      IgG suggests that individual residues, motifs, and conformations influence the
      autoantigen binding specificities that contributed to the observed differences in
      immune deposit formation.

PMID- 8990091
TI  - Studies on the structure, regulation, and pathogenic potential of anti-dsDNA
      antibodies.
AB  - Studies of anti-double-stranded (anti-ds)DNA antibodies have provided insights
      into how and why these antibodies arise in systemic lupus erythematosus. In this
      review we discuss the experimental approaches that have been used by our
      laboratory to study these autoantibodies. Structure/function analyses including
      site-directed mutagenesis have helped characterize the molecular genetics of anti
      dsDNA antibodies, and more recently peptide libraries have been used to define
      molecular motifs that these antibodies bind. Most of the pathogenic anti-dsDNA
      antibodies observed in lupus are somatically mutated. We demonstrated in vitro
      and in vivo that anti-bacterial antibodies can mutate to acquire specificity for
      dsDNA. Furthermore, using a fusion partner constitutively expressing bcl-2,
      NSO(bcl-2), we have shown the existence of anergic or preapoptotic B cells making
      antibodies that cross-react with both bacterial antigen and dsDNA. Whether
      defects in the regulation of these antibodies might contribute to serum
      expression of anti-dsDNA antibodies in some individuals remains unknown. A major
      emphasis of this review is the regulation of anti-dsDNA antibodies in a
      transgenic mouse model harboring the gene for the heavy chain of a pathogenic
      anti-dsDNA antibody. Nonautoimmune transgenic mice effectively regulate
      autoreactive B cells by anergy and deletion, while their autoimmune counterparts
      do not. The vast majority of anergic B cells expressing high-affinity transgenic
      anti-dsDNA antibody fail to display allelic exclusion of the heavy chain. We
      postulate that this may be one mechanism that allows them to escape deletion.
      Comparative studies on light chain usage in both the autoimmune and the
      nonautoimmune transgenic mouse strains have demonstrated that within the
      autoreactive B-cell population, there are subsets that are differentially
      regulated. Ultimately transgenic animals making pathogenic autoantibodies may
      provide us with a system for testing novel therapies for autoimmune disease.

PMID- 8990092
TI  - Cytokine research as one of the exciting fields in immunology.

PMID- 8990093
TI  - Epstein-Barr Virus EBNA-2 gene expression enhances lymphotoxin production by B
      lymphocytes.
AB  - Epstein-Barr Virus (EBV) effectively transforms B lymphocytes into long-term cell
      lines or tumors through the interaction of viral gene products and cellular
      proteins induced secondary to the virus infection. The latent membrane protein
      (LMP) gene, the EBV nuclear antigens (EBNAs) 1 and 2, and the origin of
      replication genes of the virus are the principal viral effectors of
      transformation. One of the cellular proteins that enhances the growth and
      proliferation of B cells is lymphotoxin (LT). We have found that Burkitt's
      lymphoma cells containing a strain of EBV with a deletion in EBNA-2 had lower
      constitutive and inducible levels of LT compared to LT production in Burkitt's
      cells with competent EBV or lymphoblastoid cell lines actively producing EBV.
      Also, the LT production in the latter cell lines was greater than in cells in
      which the infecting EBV had a deletion in the LMP gene. The relative decrease in
      LT production associated with deletions in the LMP was less than that found with
      EBNA-2 deletions. Overall our results indicate that the EBNA-2 gene enhances the
      capacity of EBV-infected cells to produce LT.

PMID- 8990094
TI  - Interleukin-5 and human B lymphocytes.
AB  - Interleukin-5 was initially characterized in murine systems, where it was found
      to have B-lymphocyte proliferative and differentiative activity and to promote
      the growth of eosinophils. Recombinant production of human IL-5 was soon
      accomplished by using murine IL-5 cDNA to isolate the highly homologous human
      sequence. Although human IL-5 was also found to be an eosinophil-active growth
      factor, a significant biologic effect of IL-5 on human B lymphocytes was
      initially difficult to demonstrate. More recently, reports from our own
      laboratory and other laboratories have provided evidence that IL-5 does have
      activity on human B lymphocytes and that human B lymphocytes may even produce IL
      5 in some situations, suggesting the possibility of autocrine stimulatory
      mechanisms. However, we and others have failed to demonstrate the known
      heterodimeric high-affinity IL-5 receptor on human B lymphocytes, in spite of
      evidence that we have accumulated suggesting that human B lymphocytes
      specifically bind IL-5. We review our own work and that of others in an area that
      will remain controversial until a human B-lymphocyte IL-5 receptor is
      definitively identified and characterized.

PMID- 8990095
TI  - B-cell-derived IL-10: production and function.
AB  - In vitro and in vivo studies identify IL-10 as a key cytokine that inhibits cell
      mediated immunity and inflammation while promoting humoral responses. The present
      review summarizes our studies regarding the ability of B cells to secrete IL-10.
      When established lines are considered, the production of human IL-10 is
      restricted to mature B-cell lines and correlates with Epstein-Barr Virus (EBV)
      expression. Accordingly, EBV infection induces purified tonsil B lym phocytes to
      produce high levels of human IL-10, whereas viral IL-10 (encoded by EBV) remains
      undetectable. Exogenous IL-10 enhances EBV-induced B-cell growth, while a
      neutralizing anti-IL-10 antibody inhibits it, suggesting that IL-10 acts as an
      autocrine growth factor for EBV-infected B lymphocytes. Normal B lymphocytes
      secrete lower levels of human IL-10 following activation through B-cell receptor
      or CD40 antigen. While addition of exogenous IL-4 diminishes CD40-induced
      secretion of IL-10, addition of Staphyloccocus aureus Cowan I (SAC) particles
      increases it. Neutralization of endogenous IL-10 does not alter growth of CD40
      activated B cells but inhibits their IgG, IgA, and IgM secretion, especially when
      costimulated with SAC particles. Finally, the simul taneous blocking of both
      endogenous IL-10 and IL-6 inhibits two-thirds of the production of the three
      isotypes when B cells were triggered through CD40 in the presence of SAC
      particles, suggesting that IL-10 synergizes with IL-6 to sustain differentiation
      of CD40-activated B lymphocytes. Overexpression of B-cell-derived IL-10 is likely
      to contribute in vivo to different pathologies such as B-lymphoproliferative
      disorders and autoimmune diseases.

PMID- 8990096
TI  - Interferon expression by B cells.
AB  - Interferons have effects on many facets of immune system development, maturation,
      and function. B cells are a target for the interferons, causing alterations in
      cell differentiation and gene expression. However, production of interferons by B
      cells has not been widely studied. In this review I will discuss the limited
      literature on B-cell interferon production. In addition I will describe results
      obtained from a transgenic model in which interferon-gamma production has been
      targeted to the B-cell compartment. In this animal, B-cell development is
      blocked, reflecting the deleterious effects that aberrant expression of
      interferon can have on this cell population.

PMID- 8990097
TI  - Interleukin-12: an immunoregulatory cytokine produced by B cells and antigen
      presenting cells.
AB  - Interleukin 12 (IL-12) is a heterodimeric protein produced by B cells, phagocytic
      cells, and other antigen-presenting cells. IL-12 was originally purified from the
      supernatant fluids of human EBV-transformed cell lines and later observed to be
      produced by the large majority of such cell lines, especially and at high levels
      from those derived from AIDS-associated lymphomas. However, phagocytic cells
      rather than B cells appear to be the most important physiological producers of IL
      12. There are two pathways of IL-12 induction in phagocytic cells: a T-cell
      independent one, induced primarily by bacteria, bacterial products, or
      intracellular parasites and important in the early inflammatory response of
      innate resistance; and a T-cell-dependent one, induced by the interaction of
      CD40L on activated T cells with CD40 receptor on IL-12-producing cells
      (phagocytic cells and antigen-presenting cells) and important in the regulation
      of adaptive immunity. IL-12 induces production of cytokines, especially
      interferon-gamma, from both T and NK cells, enhances the cytotoxic activity of NK
      cells and the generation of cytotoxic T cells, and has a proliferative activity
      on T and NK cells. Both in vivo and in vitro, IL-12 is a powerful inducer of T
      helper type 1 (Th1) response, whereas it inhibits Th2-type responses.

PMID- 8990098
TI  - Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in B-lymphocyte
      function.
AB  - Two cytokines important in the regulation of B-cell function are tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6). They act at different steps in
      B-cell differentiation and can be produced by the B cells themselves upon
      appropriate stimulation. Crosslinking of surface Ig and signaling through CD22 or
      CD40 lead to increased secretion of both cytokines. Neutralization of TNF-alpha
      or IL-6 biologic activity in B-cell cultures results in a significant reduction
      in B-cell proliferation and Ig secretion. Increased production of these cytokines
      is found in several diseases associated with aberrant B-cell function. This
      review will focus on the role of TNF-alpha and IL-6 in normal and
      pathophysiological conditions of B-cell function.

PMID- 8990099
TI  - Production and roles of IL-6, IL-10, and IL-13 in B-lymphocyte malignancies and
      in B-lymphocyte hyperactivity of HIV infection and autoimmunity.
AB  - We analyzed the production and the roles of IL-6, IL-10, and IL-13 in B-lymphoid
      malignancies and in specific diseases with B-lymphocyte hyperactivity. Both IL-13
      and IL-10 genes are expressed in B-cell lymphomas. However, their contribution to
      tumor progression is unclear. In certain lymphoproliferative disorders that
      develop in transplanted patients, IL-6 is produced by malignant cells and is a
      major factor of their proliferation. In other lymphomas, the IL-6 gene is
      expressed only in malignancies where differentiated malignant cells are present.
      In these lymphomas, IL-6 is produced by stromal cells, and the malignant cells
      express the IL-6 receptor. In patients with HIV infection, the level of
      production of IL-6, IL-10, and IL-13 is not higher than those of other conditions
      with immune activation. However, IL-6 contributes to increased production of IgG
      and IgA in vivo. In Castleman's disease, IL-6 is produced in the lymph node
      germinal centers, partly originating from follicular dendritic cells, which may
      explain some of the pathogenesis of this disease. In systemic lupus
      erythematosus, the critical cytokine is IL-10, which is produced in large amounts
      by B lymphocytes and monocytes and is responsible for autoantibody production.
      Taken together, these data emphasize the roles of IL-6 and IL-10, usually
      produced by nonlymphoid cells, on B lymphocytes, either malignant or
      hyperactivated.

PMID- 8990101
TI  - BSE inquiry could prompt censure vote.

PMID- 8990100
TI  - B-cell-derived granulocyte-colony stimulating factor (G-CSF).
AB  - Biologically active granulocyte-colony stimulating factor (G-CSF) was released
      spontaneously in culture by in vivo activated tonsillar B lymphocytes and, in
      particular, by the germinal center (GC) B-cell subset. In contrast, mantle zone B
      cells failed to produce the cytokine under any of the culture conditions tested.
      A CD40 monoclonal antibody (mAb), recombinant (r) IL4, and the combination of the
      CD40 mAb and rIL4 all increased G-CSF production by GC B cells. The augmentation
      of G-CSF release correlated with the increased survival of GC B cells. rG-CSF
      rescued GC B cells from apoptosis, suggesting that the cytokine may be utilized
      in autocrine and/or paracrine ways. Neoplastic B cells from follicular center
      cell lymphoma patients, which are the counterparts of normal GC B lymphocytes,
      also released G-CSF spontaneously in culture. In contrast, malignant B cells from
      a subset of chronic lymphocytic leukemia (CLL) patients had to be stimulated with
      Staphylococcus aureus Cowan I or CD40 mAb in combination with rIL4 or rIL2 to
      produce G-CSF in vitro. Some B-CLL cell suspensions were rescued from spontaneous
      apoptosis following culture in the presence of rG-CSF. Taken together, these
      studies provide the first demonstration that G-CSF (i) is produced by either
      normal or neoplastic human B lymphocytes and (ii) participates in the modulation
      of apoptosis of the same cells.

PMID- 8990102
TI  - 'Misconduct' dispute raises fears of litigation.

PMID- 8990103
TI  - Russian records rise in HIV.

PMID- 8990104
TI  - Safety of transgenic corn.

PMID- 8990105
TI  - Italian grants.

PMID- 8990106
TI  - In search of molecular darwinism.

PMID- 8990107
TI  - Betas are brought into the fold.

PMID- 8990108
TI  - Myxobacterial bounty.

PMID- 8990109
TI  - The alphabet of weight control.

PMID- 8990110
TI  - A vision over time and space.

PMID- 8990111
TI  - Serotonin in the spotlight.

PMID- 8990112
TI  - p53 and treatment of bladder cancer.

PMID- 8990113
TI  - Y-chromosome variation in great apes.

PMID- 8990114
TI  - Biological activation of hydrogen.

PMID- 8990115
TI  - A high deuterium abundance in the early Universe.
AB  - Intergalactic gas clouds at high redshifts have element abundances that are close
      to primordial. The ratio of deuterium to hydrogen (D/H) within such clouds-which
      is determined from absorption lines in the spectra of more distant quasars that
      lie along the same line of sight-provides the best estimate of the density of
      baryons (omegaB) in the Universe. Previous estimates of D/H in the early Universe
      have yielded values that differ by about an order of magnitude, with the lower
      values implying a high density of baryons that may be difficult to reconcile with
      both estimates of the primordial abundances of other light elements (especially
      4He) and the known number of light neutrinos. The accuracy of such D/H
      determinations is heavily dependent on the inferred column density of neutral
      hydrogen in the absorbing clouds. Here we report an independent measurement of
      the neutral hydrogen column density in the cloud towards the quasar Q1937 - 1009,
      for which one of the low D/H values was derived. Our measurement requires a
      substantial revision to the D/H value reported previously; we obtain a lower
      limit of D/H > 4 x 10(-5) for this cloud, which implies omegaB < 0.016 for a
      Hubble constant of 100 km s(-1) Mpc(-1). This reduced upper limit for the baryon
      density relieves any conflict with standard Big Bang nucleosynthesis.

PMID- 8990116
TI  - Episodic adaptive evolution of primate lysozymes.
AB  - Although the darwinian concept of adaptation was established nearly a century
      ago, it has been difficult to demonstrate rigorously that the amino-acid
      differences between homologous proteins from different species have adaptive
      significance. There are currently two major types of sequence tests for positive
      darwinian selection on proteins from different species: sequence convergence, and
      neutral rate violation (reviewed in ref. 1). Lysozymes from the stomachs of cows
      and langur monkeys, two mammalian species displaying fermentation in the foregut,
      are an example of amino-acid sequence convergence among homologous proteins. Here
      we combine tests of neutral rate violation with reconstruction of ancestral
      sequences to document an episode of positive selection on the lineage leading to
      the common ancestor of the foregut-fermenting colobine monkeys. This analysis
      also detected a previously unsuspected adaptive episode on the lineage leading to
      the common ancestor of the modern hominoid lysozymes. Both adaptive episodes were
      followed by episodes of negative selection. Thus this approach can detect
      adaptive and purifying episodes, and localize them to specific lineages during
      protein evolution.

PMID- 8990117
TI  - Abnormal temporal dynamics of visual attention in spatial neglect patients.
AB  - When we identify a visual object such as a word or letter, our ability to detect
      a second object is impaired if it appears within 400ms of the first. This
      phenomenon has been termed the attentional blink or dwell time and is a measure
      of our ability to allocate attention over time (temporal attention). Patients
      with unilateral visual neglect are unaware of people or objects contralateral to
      their lesion. They are considered to have a disorder of attending to a particular
      location in space (spatial attention). Here we examined the non-spatial temporal
      dynamics of attention in patients, using a protocol for assessing the attentional
      blink. Neglect patients with right parietal, frontal or basal ganglia strokes had
      an abnormally severe and protracted attentional blink When they identified a
      letter, their awareness of a subsequent letter was significantly diminished for a
      length of time that was three times as long as for individuals without neglect.
      Our results demonstrate for the first time that visual neglect is a disorder of
      directing attention in time, as well as space.

PMID- 8990118
TI  - Visuomotor integration is associated with zero time-lag synchronization among
      cortical areas.
AB  - Information processing in the cerebral cortex invariably involves the activation
      of millions of neurons that are widely distributed over its various areas. These
      distributed activity patterns need to be integrated into coherent
      representational states. A candidate mechanism for the integration and
      coordination of neuronal activity between different brain regions is
      synchronization on a fine temporal scale. In the visual cortex, synchronization
      occurs selectively between the responses of neurons that represent related
      features and that need to be integrated for the generation of coherent percepts;
      neurons in other areas of the cerebral cortex also synchronize their discharges.
      However, little is known about the patterns and the behavioural correlates of
      synchrony among widely separated cortical regions. Here we report that
      synchronization occurs between areas of the visual and parietal cortex, and
      between areas of the parietal and motor cortex, in the awake cat. When cats
      responded to a sudden change of a visual pattern, neuronal activity in cortical
      areas exhibited synchrony without time lags; this synchrony was particularly
      strong between areas subserving related functions. During reward and inter-trial
      episodes, zero-time-lag synchrony was lost and replaced by interactions
      exhibiting large and unsystematic time lags.

PMID- 8990119
TI  - In vivo dendritic calcium dynamics in neocortical pyramidal neurons.
AB  - The dendrites of mammalian pyramidal neurons contain a rich collection of active
      conductances that can support Na+ and Ca2+ action potentials (for a review see
      ref. 1). The presence, site of initiation, and direction of propagation of Na+
      and Ca2+ action potentials are, however, controversial, and seem to be sensitive
      to resting membrane potential, ionic composition, and degree of channel
      inactivation, and depend on the intensity and pattern of synaptic stimulation.
      This makes it difficult to extrapolate from in vitro experiments to the situation
      in the intact brain. Here we show that two-photon excitation laser scanning
      microscopy can penetrate the highly scattering tissue of the intact brain. We
      used this property to measure sensory stimulus-induced dendritic [Ca2+] dynamics
      of layer 2/3 pyramidal neurons of the rat primary vibrissa (Sm1) cortex in vivo.
      Simultaneous recordings of intracellular voltage and dendritic [Ca2+] dynamics
      during whisker stimulation or current injection showed increases in [Ca2+] only
      in coincidence with Na+ action potentials. The amplitude of these [Ca2+]
      transients at a given location was approximately proportional to the number of
      Na+ action potentials in a short burst. The amplitude for a given number of
      action potentials was greatest in the proximal apical dendrite and declined
      steeply with increasing distance from the soma, with little Ca2+ accumulation in
      the most distal branches, in layer 1. This suggests that widespread Ca2+ action
      potentials were not generated, and any significant [Ca2+] increase depends on
      somatically triggered Na+ action potentials.

PMID- 8990120
TI  - Role of melanocortinergic neurons in feeding and the agouti obesity syndrome.
AB  - Dominant alleles at the agouti locus (A) cause an obesity syndrome in the mouse,
      as a consequence of ectopic expression of the agouti peptide. This peptide,
      normally only found in the skin, is a high-affinity antagonist of the melanocyte
      stimulating hormone receptor (MC1-R), thus explaining the inhibitory effect of
      agouti on eumelanin pigment synthesis. The agouti peptide is also an antagonist
      of the hypothalamic melanocortin-4 receptor (MC4-R). To test the hypothesis that
      agouti causes obesity by antagonism of hypothalamic melanocortin receptors, we
      identified cyclic melanocortin analogues that are potent agonists or antagonists
      of the neural MC3 (refs 11, 12) and MC4 receptors. Intracerebroventricular
      administration of the agonist, MTII, inhibited feeding in four models of
      hyperphagia: fasted C57BL/6J, ob/ob, and A(Y) mice, and mice injected with
      neuropeptide Y. Co-administration of the specific melanocortin antagonist and
      agouti-mimetic SHU9119 completely blocked this inhibition. Furthermore,
      administration of SHU9119 significantly enhanced nocturnal feeding, or feeding
      stimulated by a prior fast. Our data show that melanocortinergic neurons exert a
      tonic inhibition of feeding behaviour. Chronic disruption of this inhibitory
      signal is a likely explanation of the agouti obesity syndrome.

PMID- 8990121
TI  - Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto
      oncogene product.
AB  - The oncogenic protein Vav harbours a complex array of structural motifs,
      including leucine-rich, Dbl-homology, pleckstrin-homology, zinc-finger, SH2 and
      SH3 domains. Upon stimulation by antigens or mitogens, Vav becomes phosphorylated
      on key tyrosine residues and associates with other signalling proteins, including
      the mitogen receptors Zap-70 (ref. 6), Vap-1 (ref. 5) and Slp-76 (ref. 7).
      Disruption of the vav locus by homologous recombination causes severe defects in
      signalling by primary antigen receptors, leading to abnormal lymphocyte
      proliferation and lymphopenia. Despite the importance of Vav cell signalling, the
      function of this protein remains unknown. Here we show that tyrosine
      phosphorylated Vav, but not the non-phosphorylated protein, catalyses GDP/GTP
      exchange on Rac-1, a protein implicated in cell proliferation and cytoskeletal
      organization, causing this GTPase to switch from its inactive to its active
      state. Transfection experiments also show that phosphorylation of Vav on tyrosine
      residues leads to nucleotide exchange on Rac-1 in vivo and stimulates c-Jun
      kinase, a downstream element in the signalling pathway involving this GTPase. Our
      results have identified a function for Vav and define a mechanism in which
      engaged membrane receptors activate its signalling pathway.

PMID- 8990123
TI  - Structure of the single-stranded-DNA-binding domain of replication protein A
      bound to DNA.
AB  - The single-stranded-DNA-binding proteins (SSBs) are essential for DNA function in
      prokaryotic and eukaryotic cells, mitochondria, phages and viruses. The
      structures of four SSBs have been solved, but the molecular details of the
      interaction of SSBs with DNA remain speculative. We report here the crystal
      structure at 2.4 A resolution of the single-stranded-DNA-binding domain of human
      replication protein A (RPA) bound to DNA. Replication protein A is a
      heterotrimeric SSB that is highly conserved in eukaryotes. The largest subunit,
      RPA70, binds to single-stranded (ss)DNA and mediates interactions with many
      cellular and viral proteins. The DNA-binding domain, which lies in the middle of
      RPA70, comprises two structurally homologous subdomains oriented in tandem. The
      ssDNA lies in a channel that extends from one subdomain to the other. The
      structure of each RPA70 subdomain is similar to those of the bacteriophage SSBs,
      indicating that the mechanism of ssDNA-binding is conserved.

PMID- 8990122
TI  - Unusual Rel-like architecture in the DNA-binding domain of the transcription
      factor NFATc.
AB  - Transcription factors of the NFAT family regulate the production of effector
      proteins that coordinate the immune response. The immunosuppressive drugs FK506
      and cyclosporin A (CsA) act by blocking a Ca2+-mediated signalling pathway
      leading to NFAT. Although FK506 and CsA have enabled human organs to be
      transplanted routinely, the toxic side-effects of these drugs limit their usage.
      This toxicity might be absent in antagonists that target NFAT directly. As a
      first step in the structure-based search for NFAT antagonists, we now report the
      identification and solution structure of a 20K domain of NFATc (NFATc-DBD) that
      is both necessary and sufficient to bind DNA and activate transcription
      cooperatively. Although the overall fold of the NFATc DNA-binding domain is
      related to that of NF-kappaB p50 (refs 2, 3), the two proteins use significantly
      different strategies for DNA recognition. On the basis of these results, we
      present a model for the cooperative complex formed between NFAT and the mitogenic
      transcription factor AP-1 on the interleukin-2 enhancer.

PMID- 8990124
TI  - Methylazoxymethanol acetate-induced apoptosis in the external granule cell layer
      of the developing cerebellum of the rat is associated with strong c-Jun
      expression and formation of high molecular weight c-Jun complexes.
AB  - Intraperitoneal administration of methylazoxymethanol (MAM) acetate (0.05
      microl/g of body weight) in male Sprague-Dawley rats aged 3 days produced cell
      death in the external granule layer of the cerebellum which peaked at 48 hours
      (h) and was followed by removal of cellular debris at 72 h. Dying cells had the
      morphological features of apoptosis and were stained with the method of in situ
      labeling of nuclear DNA fragmentation. Strong c-Jun immunoreactivity was observed
      in apoptotic cells during the whole process of MAM-induced apoptosis. No
      differences of c-Fos immunoreactivity were observed between control and MAM
      treated rats throughout the period studied. Western blotting of cerebellar
      homogenates in control rats disclosed two bands which reacted with both c-Jun
      antibodies, one located at p39 that corresponds to the molecular weight of c-Jun,
      and the other at about p62. MAM-treated rats showed a robust band at p62,
      together with a thinner band located immediately above it, which was accompanied
      by a reduction of the p39 band. The specificity of the immunoreaction was tested
      by incubating the antibodies with the appropriate control peptides. No difference
      between control and MAM-treatad rats was observed in Western blots processed with
      antibodies to c-Fos during this study. These results show that MAM-induced
      apoptosis in the external granule cell layer of the rat is associated with strong
      c-Jun expression, which is restricted to apoptotic cells, and with the formation
      of high-molecular-weight c-Jun complexes. Taken together, the present
      observations suggest that c-Jun may participate in the genetic cascade of events
      leading to apoptotic cell death in the developing cerebellum.

PMID- 8990125
TI  - Immunocytochemical characterization of the expression of inducible and
      constitutive isoforms of nitric oxide synthase in demyelinating multiple
      sclerosis lesions.
AB  - The cellular localization and distribution of inducible and constitutive nitric
      oxide synthase (iNOS/cNOS) was determined in tissue sections from multiple
      sclerosis (MS) and control brain and spinal cord. Immunocytochemical techniques
      were applied using specific iNOS- and cNOS-directed antibodies. In addition,
      NADPH-diaphorase histochemistry was performed. To establish the identity of iNOS
      , cNOS- and NADPH-diaphorase-positive cells single and double staining was
      performed on tissue sections with the macrophage marker KP1 (CD68) and with the
      astrocyte marker glial fibrillary acidic protein (GFAP). Areas of myelin
      breakdown and demyelination were determined using a staining for neutral lipids,
      Oil Red O (ORO). Furthermore, macrophages isolated from active demyelinating MS
      lesions were stained for iNOS, cNOS, KP1 and ORO. In active MS lesions strong
      iNOS immunoreactivity was found exclusively in perivascular and parenchymal
      macrophages distributed within regions of active demyelination. In these active
      MS lesions immunoreactivity for cNOS was also found in macrophages. Macrophages
      isolated from active MS lesions also showed immunoreactivity for iNOS and cNOS.
      Moreover, these isolated macrophages produced nitric oxide (NO; >30 microM) in
      vitro. NADPH-diaphorase activity was detected in KP1-positive perivascular and
      parenchymal macrophages and in GFAP-positive reactive astrocytes in active MS
      lesions and in reactive astrocytes located in the hypercellular rims of chronic
      active MS lesions. cNOS-positive reactive astrocytes were detected in both active
      and chronic active MS lesions. Inside chronic active lesions some residual
      macrophages were weakly iNOS-positive. In control brain and spinal cord no iNOS
      immunoreactivity could be detected. These results suggests an important role for
      human macrophages capable of producing the free radical nitric oxide (NO), which
      may contribute to the cytotoxicity of oligodendrocytes and destruction of myelin
      in MS brain and spinal cord.

PMID- 8990126
TI  - Altered calcium homeostasis and ultrastructure in motoneurons of mice caused by
      passively transferred anti-motoneuronal IgG.
AB  - Calcium homeostasis and ultrastructure are altered in motor axon terminals (AT)
      of amyotrophic lateral sclerosis (ALS) patients and in mice injected with ALS IgG
      and exhibit increased density of synaptic vesicles and increased intracellular
      calcium. To develop an immune-mediated passive transfer experimental model of
      both systemic weakness and altered morphology, mice were inoculated
      intraperitoneally with anti-motoneuronal IgG. Animals initially manifested muscle
      stiffness and evidence of autonomic cholinergic hyperactivity. Electron
      microscopic cytochemistry within 12 hours (h) demonstrated significantly
      increased density of synaptic vesicles and calcium both in axon terminals of
      neuromuscular junctions and synaptic boutons on spinal motoneurons. After 24 h
      the mice were severely weak and premorbid. The number of synaptic vesicles was
      still larger than normal, but calcium was depleted from axon terminals and
      synaptic boutons. The motoneuron perikarya demonstrated the dilatation of the
      Golgi system and the rough endoplasmic reticulum with an increased amount of
      calcium. The NMDA receptor antagonist, MK-801, and the L-type calcium channel
      antagonist, Diltiazem, prevented clinical symptoms and some morphological
      alterations. These data demonstrate that high titer anti-motoneuronal IgG can
      induce severe weakness and produce similar ultrastructural features of motor axon
      terminals in human ALS and in mice injected with ALS IgG, and support a key role
      for calcium in selective vulnerability of motoneurons.

PMID- 8990127
TI  - Developmental regulation of presenilin mRNA expression parallels notch
      expression.
AB  - Mutations in the presenilin (PS) 1 and 2 genes are associated with autosomal
      dominant Alzheimer disease. PS1 shares striking homology with sel-12, a C.
      elegans gene implicated in the function of lin-12/Notch, a protein important in
      neurogenesis. We studied mRNA expression using RT-PCR and in situ hybridization
      techniques during neural development in mouse and rat. Strong expression of PSs
      and Notch1 was observed in embryos, especially in the ventricular zone, which
      decreased gradually as embryos developed. Very low levels of PSs and Notch were
      present in adulthood, their signals present primarily in the hippocampus and
      cerebellum. These observations show that, like Notch, PS1 and PS2 are strongly
      developmentally regulated, and support the plausibility of an interaction between
      PSs and Notch.

PMID- 8990128
TI  - Exercise induces myonuclear ubiquitination and apoptosis in dystrophin-deficient
      muscle of mice.
AB  - Apoptosis plays a major role in several diseases, including viral infections,
      autoimmune diseases, cancer, cardiac infarct, and neurological disorders. To
      investigate the role of apoptosis in muscular dystrophy, dystrophin-deficient
      (mdx) mice were subjected to spontaneous exercise and skeletal muscles were
      analyzed for apoptosis and ubiquitin. The increase of apoptotic myonuclei after
      exercise was detected by TUNEL, by electron microscopy, and by DNA analyses for
      high molecular weight and for ladder fragments. Expression of ubiquitin
      correlated with exercise and with positive myonuclei for apoptosis. Biochemical
      analysis confirmed a high level of ubiquitination both in sarcoplasmic and
      myofibrillar proteins. Muscles from sedentary congenit control mice (C57B ) were
      negative for apoptosis, while after exercise some nuclei were positive. We also
      revealed that normal myoblasts committed to apoptosis in vitro showed an
      increased expression of ubiquitin. Western blot for bcl-2, FasL, and BAG1 showed
      a significant decrease of bcl-2 product only in mdx mice after exercise. Thus,
      spontaneous exercise results in the increase of ubiquitin expression and in the
      reduction of bcl-2 tightly related to programmed cell death in mdx mice. These
      findings confirm that DNA fragmentation, absent in muscles of sedentary normal
      mice but present in mdx mice at rest, dramatically increases after exercise,
      shedding new light on exercise-induced muscle damage and on its progression in
      dystrophinopathies.

PMID- 8990129
TI  - Increased apoptosis of T lymphocytes and macrophages in the central and
      peripheral nervous systems of Lewis rats with experimental autoimmune
      encephalomyelitis treated with dexamethasone.
AB  - Using light and electron microscopic histological and immunocytochemical
      techniques, we investigated the effects of the glucocorticoid dexamethasone on T
      cell and macrophage apoptosis in the central nervous system (CNS) and peripheral
      nervous system (PNS) of Lewis rats with acute experimental autoimmune
      encephalomyelitis (EAE) induced with myelin basic protein (MBP). A single
      subcutaneous injection of dexamethasone markedly augmented T cell and macrophage
      apoptosis in the CNS and PNS and microglial apoptosis in the CNS within 6 hours
      (h). Pre-embedding immunolabeling revealed that dexamethasone increased the
      number of apoptotic CD5+ cells (T cells or activated B cells), alphabeta T cells,
      and CD11b+ cells (macrophages/microglia) in the meninges, perivascular spaces,
      and CNS parenchyma. The induction of increased apoptosis was dose-dependent.
      Daily dexamethasone treatment suppressed the neurological signs of EAE. However,
      the daily injection of a dose of dexamethasone (0.25 mg/kg), which, after a
      single dose, did not induce increased apoptosis in the CNS or PNS, was as
      effective in inhibiting the neurological signs of EAE as the high dose (4 mg/kg),
      which induced a marked increase in apoptosis. This indicates that the beneficial
      clinical effect of glucocorticoid therapy in EAE does not depend on the induction
      of increased apoptosis. The daily administration of dexamethasone for 5 days
      induced a relapse that commenced 5 days after cessation of treatment, with the
      severity of the relapse tending to increase with dexamethasone dosage.

PMID- 8990130
TI  - Distribution, levels, and activity of glycogen synthase kinase-3 in the Alzheimer
      disease brain.
AB  - A number of studies have implicated a proline-directed protein kinase, glycogen
      synthase kinase-3 (GSK-3) in the hyperphosphorylation of tau in Alzheimer's
      disease (AD). Toward understanding the role of GSK-3 in the abnormal
      hyperphosphorylation of tau in AD we have found that GSK-3 is prominently present
      in neuronal cell bodies and their processes and co-localizes with neurofibrillary
      changes in AD brain. Furthermore, the levels of GSK-3 as determined by indirect
      ELISA are approximately 50% increased in the postsynaptosomal supernatant from AD
      brains as compared to the controls. However, no increase in GSK-3 enzyme activity
      was detected. In AD brain, with its reduced phosphatase activity, even normal
      levels of GSK-3 activity might be sufficient for the hyperphosphorylation of tau.

PMID- 8990131
TI  - Paired helical filaments are twisted ribbons composed of two parallel and aligned
      components: image reconstruction and modeling of filament structure using atomic
      force microscopy.
AB  - To study the structure of Alzheimer paired helical filaments (PHF) we examined
      isolated detergent-insoluble PHF using atomic force microscopy with image
      reconstruction. The reconstructed AFM images of Alzheimer PHF most closely
      resembled ribbon-like helices with thin edges. The presence of a conspicuous
      furrow in the PHF midline indicated that PHF were composed of two distinctive
      strands. Our present conception of the overall configuration of PHF is consistent
      with that proposed by Crowther and Wischik in 1985 but includes an essential
      component of the prevailing model: the presence of two strands. Thus, our new
      model of PHF structure, based on atomic force microscopy-derived data, indicates
      that the true structure of PHF is actually a hybrid of the prevailing PHF model
      and a thin helical ribbon.

PMID- 8990132
TI  - Bax protein expression is increased in Alzheimer's brain: correlations with DNA
      damage, Bcl-2 expression, and brain pathology.
AB  - We have shown that many neurons in Alzheimer's disease (AD) exhibit terminal
      deoxynucleotidyl transferase (TdT) labeling for DNA strand breaks, and
      upregulation of Bcl-2 is associated with neurons exhibiting nuclear DNA
      fragmentation, while downregulation of Bcl-2 is associated with tangle-bearing
      neurons in AD brains. Consequently, we examined the expression of bcl-associated
      X (Bax) protein in AD brain. Immunoreactivity for Bax was seen in neurons and
      microglia of the hippocampal formation, and was elevated in the majority of AD
      cases as compared to control cases. Interestingly, 3 transitional cases, which
      had mild degeneration changes, exhibited relatively high levels of Bax
      immunoreactivity. Most Bax-positive neurons showed either TdT-labeled nuclei or
      Bcl-2 immunoreactivity. Although Bax immunoreactivity was detected within most
      early tangle-bearing neurons, many Bax-positive neurons did not colocalize with
      later-stage tangle-bearing neurons. In regions containing relatively few tangles
      in mild AD brains, many TdT-labeled neurons were immunolabeled with Bax antibody
      and most of them lacked evidence of neurofibrillary changes. These findings
      suggest that Bax may contribute to neuronal cell death in AD. Furthermore, DNA
      damage and the upregulation of Bax appear to precede tangle formation or may
      represent an alternative pathway of cell death in AD.

PMID- 8990133
TI  - Preferential subsarcolemmal localization of dystrophin and beta-dystroglycan mRNA
      in human skeletal muscles.
AB  - The intracellular localization of dystrophin and beta-dystroglycan mRNA in
      skeletal muscles of patients with Duchenne muscular dystrophy (DMD) or Becker
      muscular dystrophy (BMD) and normal subjects was examined by in situ
      hybridization using biotinylated oligonucleotide probes. These mRNAs were found
      preferentially in sarcolemma in the skeletal muscles of both normal subjects and
      affected patients. Quantitative analysis of mRNA signals demonstrated no
      prominent reduction of dystrophin or beta-dystroglycan mRNA in DMD/BMD muscles.
      These results suggest that even mRNAs with deletions contain specific information
      that affects their localization, and the characteristic defect of dystrophin in
      DMD/BMD muscles seems to be caused mainly by the instability of dystrophin
      protein, as a post-transcriptional event.

PMID- 8990134
TI  - "Increasing brain tumor rates: is there a link to aspartame?".

PMID- 8990135
TI  - "Increasing brain tumor rates: is there a link to aspartame?".

PMID- 8990136
TI  - Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic
      findings in 80 cases.
AB  - Renal oncocytoma has several features that overlap with other renal neoplasms
      with a preponderance of granular cytoplasm, such as chromophobe, granular, and
      papillary renal cell carcinomas. Lack of knowledge of this entire spectrum of
      eosinophilic renal cell neoplasms has led to several misconceptions in the
      literature regarding renal oncocytoma. These include the "grading of
      oncocytomas," "metastatic oncocytomas," and the impression that renal oncocytoma
      is usually low grade and lacks prominent nucleoli. In order to further
      characterize the histologic features and embelLish diagnostic criteria, we
      evaluated 93 tumors from 80 patients. Four tumors were bilateral and two were
      multifocal. The mean age was 67.2 years (32-89 years), men were more commonly
      affected (3.1:1), and 82.7% tumors were incidental findings. Grossly, the tumors
      were mahogany brown, lacked necrosis, and averaged 4.4 cm in size (range 0.6-15
      cm). Histologically, renal oncocytoma was composed of an exclusive or predominant
      component of acidophilic cells with three architectural patterns of disposition:
      (a) The "classic" pattern (57.5%), composed of a characteristic nested or
      organoid arrangement of cells, each surrounded by a distinct reticulin framework;
      (b) a "tubulocystic pattern" (6.3%) with numerous closely packed cystically
      dilated tubular structures; and (c) "mixed pattern" (36.2%), which had both the
      organoid and tubulocystic patterns. A gross or microscopic scar was noted in
      53.8% cases, and histologically a distinctive myxoid and/or hyalinized stroma
      separated nests of cells. Generally, the nuclei of renal oncocytoma were round
      with uniform nuclear contours. Nearly half of the tumors had prominent nucleoli
      (42.5% had prominent nucleoli equivalent to Fuhrman's grade III or IV).
      Pleomorphism was absent in 50% of cases but was conspicuous in 12.5% of cases
      including foci of bizarre cells. Other atypical features included perinephric fat
      involvement (11.3%), renal parenchymal invasion not associated with desmoplasia
      (10%), and hemorrhage (31.3%). Renal oncocytoma by definition lacks areas of
      clear cell carcinoma, significant lesional necrosis, or conspicuous papillary
      formations. Ancillary features noted included normal-appearing renal tubules
      within the lesion (15%), intranuclear holes (20%), psammoma bodies (7.5%), and
      foam cells (7.5%). 15% of tumors were locally excised, and 85% resulted in
      radical nephrectomy. Mean follow-up of 7.6 years (range 15-200 months) showed no
      evidence of recurrence, metastasis, or death due to tumor. In conclusion, renal
      oncocytoma, herein described, is a benign neoplasm and therefore does not merit a
      nuclear grading scheme. It has unique histologic features including an organoid
      and tubulocystic architecture, myxoid or hyalinized stroma, and occasionally some
      atypical findings including nuclear pleomorphism, prominent nucleoli, and
      adjacent renal parenchymal and perinephric fat involvement.

PMID- 8990137
TI  - Mixed tumors and myoepitheliomas of soft tissue: a clinicopathologic study of 19
      cases with a unifying concept.
AB  - We report 19 unusual cases of mixed tumors and myoepitheliomas arising in soft
      tissues. The neoplasms occurred in 12 males and seven females. The age at
      diagnosis ranged from 2 to 83 years (mean 35, median 30). Eight tumors arose in
      the upper limb, six in the lower limb, three in the trunk, and two in the head
      and neck region. Three cases involved both dermis and subcutis; the remainder
      arose in subcutaneous (13 cases) or deep subfascial soft tissue (three cases).
      The most common presenting complaint was a painless swelling, with duration
      ranging from 2 weeks to 1 year (median 2.5 months). Microscopically, the tumors
      were predominantly well circumscribed and lobulated. Six cases showed a focally
      infiltrative margin. Cardinal morphologic features included nests, cords, and
      ductules of epithelioid cells and/or nests of spindled cells within a hyalinized
      to chondromyxoid stroma. One tumor was predominantly composed of myoepithelial
      cells and devoid of epithelial differentiation (i.e., ductules). Cytoplasmic
      hyaline inclusions were noted in two cases; squamous differentiation was seen in
      one case. Osteoid production and/or metaplastic bone was observed in three
      tumors. Chondroid differentiation (usually mature) was seen in four cases.
      Adipocytic differentiation was seen in two tumors. Mitotic activity was variable
      but generally scant; atypical mitotic figures were not identified. By
      immunohistochemistry, 16 of 16 cases expressed pan-keratin; 16 of 17 S-100
      protein; six of 14 alpha smooth muscle actin (IA4); two of 10 muscle specific
      actin (HHF-35); two of 10 desmin; three of 11 glial fibrillary acidic protein;
      and three of 16 epithelial membrane antigen. Clinical follow-up was available in
      10 patients and ranged from 6 months to 20 years (mean 4.25 years, median 2
      years). Two patients developed local recurrence; metastasis to lung and lymph
      nodes were observed in two additional patients. Both of the latter patients died.
      We believe that these findings expand the concept of cutaneous mixed tumors to
      include neoplasms composed predominantly of myoepithelial cells and to include
      tumors arising in deeper subcutaneous and/or subfascial tissues. The clinical
      behavior of such neoplasms, when arising in soft tissues, may be difficult to
      predict but is most often benign; however, a minority of lesions metastasize.
      Until larger studies with longer follow-up are available, treatment and
      prognostication are probably best based on criteria used in comparable salivary
      gland tumors.

PMID- 8990138
TI  - Immunohistochemical study of skin lesions in acute and chronic graft versus host
      disease following bone marrow transplantation.
AB  - Allogeneic bone marrow transplantation (BMT) is the therapy of choice for a
      variety of malignant and nonmalignant disorders; however, a major constraint to
      successful BMT is graft versus host disease (GVHD). Skin lesions are the earliest
      presentation of GVHD. Donor-derived cytotoxic T lymphocytes are the effector
      cells responsible for lesions in the skin and other tissues. Here we show that
      most skin-infiltrating lymphocytes, in all forms of GVHD, are memory T cells with
      a predominance of CD4+ cells in the dermis and CD8+ cells in the epidermis.
      Relatively little attention has been focused on the adhesive phenotype of
      keratinocytes in GVHD. In this study, immunohistochemical analyses of skin
      biopsies from BMT patients with acute or chronic GVHD were conducted, with
      particular emphasis on antigen-presenting cells (APCs) and on keratinocytes. The
      distribution of APCs in the epidermis (Langerhans' cells) was investigated.
      Keratinocytes were analyzed for the expression of human leukocyte antigen DR
      locus (HLA-DR) and of a novel integrin, alpha10.1.2 beta1, which is detected in
      the basal layer of normal epidermis. Langerhans' cells were decreased in all
      grades of acute GVHD, but the epidermal APC network was reconstituted in chronic
      GVHD. HLA-DR was expressed by keratinocytes in grade 2 and 3 acute GVHD lesions,
      but not in two of three chronic GVHD cases, and in the regression phase of acute
      GVHD. Integrin chains alpha10.1.2 and beta1 were detected in the epidermal basal
      cell layer of most GVHD cases but they were also expressed in suprabasal
      keratinocytes of both acute and chronic GVHD. This latter finding indicates that
      a proliferative response uncoupled from differentiation occurs in keratinocytes
      in the course of GVHD.

PMID- 8990139
TI  - Histopathological study of Sauropus androgynus-associated constrictive
      bronchiolitis obliterans: a new cause of constrictive bronchiolitis obliterans.
AB  - The development of constrictive bronchiolitis obliterans in patients who have
      ingested Sauropus androgynus juice has not been previously reported. We describe
      four patients with S. androgynus-associated constrictive bronchiolitis obliterans
      who underwent open lung biopsies for histopathological analysis. This article
      aims to recognize the possible pathogenesis of the disease. The spectrum of
      histologic changes ranged from slight bronchiolar inflammation and fibrosis to
      marked submucosal fibrosis causing complete cicatricial obliteration of the
      lumen. A dense eosinophil infiltrate was noted in the bronchiolar submucosa or
      fibrotic tissue of the completely obliterated bronchioles in two patients.
      Immunohistochemical studies revealed that lymphocytic infiltrate consisted mainly
      of T lymphocytes in all patients. Immunofluorescent stains for immunoglobulin
      (Ig)G, IgA, IgM, C1q, C3, and C4 were negative. Electron microscopy disclosed no
      immune complex deposition in the specimens examined. Although the role of
      antibody- and complement-mediated reaction is not supported by the negative
      results of immunofluorescent and electron microscopic studies, the common finding
      of the predominant T-lymphocytic infiltrate suggests that a T-cell mediated
      immune response is involved in the pathogenesis of the disease. Furthermore, the
      finding of a heavy lymphocytic infiltrate in many bronchioles without significant
      collagen deposition suggests that the lymphocytic infiltrate may precede the
      tissue fibrosis. In addition, the presence of a dense eosinophil infiltrate may
      combine with lymphocytes and other immunologic and mesenchymal cells to promote
      antigen-specific stimulation of lymphocytes and induction of fibrosis.

PMID- 8990140
TI  - True papillary carcinoma of the lung: a distinct clinicopathologic entity.
AB  - There continues to be confusion as to whether papillary adenocarcinoma (PA) of
      the lung is a specific histologic entity or simply a variant of
      bronchioloalveolar carcinoma (BAC). We reviewed our files from 1981 through 1993
      for all cases (n = 155) of resected primary lung adenocarcinoma specifically
      diagnosed as having papillary or bronchioloalveolar features. In addition, a
      random 10% (n = 67) of all remaining lung adenocarcinomas were reviewed. True PA
      was diagnosed when > or = 75% of the neoplasm contained papillary structures
      supported by fibrovascular cores with complicated secondary and tertiary
      branches. Marked nuclear atypia was present in 100%, and psammoma bodies were
      seen in 42% of cases. In contrast to BAC, true PA filled and distorted or
      replaced air spaces in the lung. Thirty-one cases of true PA were found,
      including 19 men and 12 women (mean age, 64.5 years). The lesions were solitary
      (n = 27) or multifocal (n = 4) with a mean diameter of 4.1 cm. Forty-five percent
      of patients had bronchopulmonary lymph node involvement at diagnosis; another 10%
      had extensive intrapulmonary lymphatic permeation by tumor. Disease-free survival
      for stage I and II PA was 40% (n = 15) and 25% (n = 8), respectively, at a mean
      of 3.4 and 3.5 years. Papillary adenocarcinoma of the lung is a distinct
      clinicopathologic entity with considerably worse morbidity and mortality than
      BAC.

PMID- 8990142
TI  - Necrosis of the gastrointestinal tract in uremic patients as a result of sodium
      polystyrene sulfonate (Kayexalate) in sorbitol: an underrecognized condition.
AB  - Sodium polystyrene sulfonate (Kayexalate) in sorbitol given as an enema or orally
      to treat hyperkalemia has been reported to induce intestinal necrosis in uremic
      patients. We studied the clinical and pathologic features of 15 patients in whom
      Kayexalate crystals were observed in specimens from gastrointestinal surgical
      resections (n = 9) or endoscopic biopsies (n = 7). Oral or nasogastric tube
      administration of Kayexalate in sorbitol was documented in 10 patients. Among 12
      patients with colorectal specimens, necrosis was observed in nine patients (75%),
      represented by seven of eight surgical resection specimens and three of five
      endoscopic biopsy specimens. No other cause of colorectal necrosis apart from
      Kayexalate in sorbitol was apparent in seven patients, and four also had necrosis
      of the small intestine. Four patients with colonic necrosis in their initial
      resection specimen developed progressive necrosis of the small intestine or
      rectum, and five patients (56%) had fatal outcome within 1 day to 6 weeks.
      Kayexalate crystals were observed in upper gastrointestinal tract specimens from
      four patients, including one with hemorrhagic gastritis. Our findings provide
      additional evidence that Kayexalate in sorbitol administered orally or by
      nasogastric tube can produce necrosis in the gastrointestinal tract.

PMID- 8990141
TI  - Fibrosarcoma versus cellular fibroma of the ovary: a comparative study of their
      proliferative activity and chromosome aberrations using MIB-1 immunostaining, DNA
      flow cytometry, and fluorescence in situ hybridization.
AB  - We retrospectively analyzed the proliferative activity and the centromeric copy
      number of chromosomes 8, 12, and 17 in three cases of fibrosarcoma and eight
      cases of cellular fibroma of the ovary using MIB-1 immunostaining, DNA flow
      cytometry, and fluorescence in situ hybridization (FISH) on paraffin-embedded
      tissue specimens. In our study, both the MIB-1 labeling index (LI) and the
      proliferative index (% of cells in S + G2 + M phase) in fibrosarcomas were higher
      than those in cellular fibromas. The FISH analysis demonstrated the sole
      abnormality of a gain of trisomy 12 cells in all eight cases of cellular fibroma.
      Both a gain of trisomy 12 cells and a gain of tetrasomy 12 cells were observed in
      one case of fibrosarcoma. A gain of trisomy 8 cells was observed in all two
      fibrosarcomas in which signals were detected. By contrast, neither a gain of
      trisomy 8 cells nor a gain of tetrasomy 12 cells was observed in any of the eight
      cases of cellular fibroma. Chromosome 17 showed disomy in all eleven cases. On
      the basis of these findings, a gain of trisomy 8 cells is therefore considered to
      be an adequately effective marker to distinguish between cellular fibroma and
      fibrosarcoma of the ovary, and it may also be related to the proliferative
      activity of fibrosarcoma of the ovary.

PMID- 8990143
TI  - Pancreatic mucinous cystic neoplasm with sarcomatous stroma: a report of three
      cases.
AB  - Three patients with pancreatic mucinous cystic neoplasms having a sarcomatous
      stroma are reported. The tumors occurred in two women and one man, aged 48, 66,
      and 67 years, respectively. Symptoms included epigastric pain or a palpable
      abdominal mass or both. Radiographically, all the tumors were large, multicystic,
      and located in the tail of the pancreas. Histologically, the cystic component was
      lined by mucin-producing, columnar to cuboidal epithelium composed of benign to
      atypical to overtly malignant cells (cystadenocarcinoma). Immunohistochemistry
      showed the epithelial component of all three tumors to be positive with
      cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and the
      pancreatic epithelial mucin antibodies CA 19-9 and DUPAN 2. In all three cases,
      an undifferentiated malignant spindle cell (sarcomatous) stroma was intimately
      associated with the epithelial component. The sarcomatous component showed
      variable reactivity with vimentin (all three cases), muscle-specific and smooth
      muscle actin (all three cases), S-100 protein (1/3), Leu-7 (one case), and
      estrogen and progesterone receptors (in two cases). Two patients died with
      widespread abdominal disease within 15 months of diagnosis, one of whom had an
      omental metastasis entirely composed of the sarcomatous stroma. The third patient
      was alive and free of disease at 16 months after diagnosis. Our findings document
      the existence of a sarcomatous component in pancreatic mucinous cystic neoplasms;
      this component appears to be responsible for the highly malignant behavior of the
      tumors.

PMID- 8990144
TI  - Primary low-grade B-cell lymphoma of the dura: a mucosa associated lymphoid
      tissue-type lymphoma.
AB  - The clinicopathologic findings in five patients with primary low-grade B-cell
      lymphoma of the intracranial dura are described. All patients were women, 40-62
      years of age, who presented with focal neurologic symptoms. Radiologic studies
      showed a well-localized dural mass in each case, raising a preoperative diagnosis
      of meningioma. Cytologically these were composed of a diffuse infiltrate of small
      lymphocytes with plasmacytoid differentiation, with a variable admixture of
      centrocytelike cells. Lambda light chain restriction was found in three cases,
      and kappa light chain in one. VJ polymerase chain reaction for immunoglobulin
      heavy-chain rearrangement was positive in three of four cases, including one case
      in which immunostaining results were equivocal. Staging procedures did not show
      involvement at any other site. Therapy consisted of radiation (n = 3),
      chemotherapy (n = 1), or both (n = 1), with excellent response. There was no
      evidence of recurrence or subsequent dissemination at follow-up of up to 63
      months. Low-grade B-cell lymphomas arising in the intracranial dura are rare but
      appear to be similar to other low-grade B-cell lymphomas arising in extranodal
      sites in terms of clinical presentation as stage 1E disease, indolent behavior,
      and favorable response to treatment, suggesting that they may be part of the
      mucosa associated lymphoid tissue (MALT) lymphoma spectrum. They appear to arise
      at dural sites where meningothelial cells are concentrated.

PMID- 8990145
TI  - Apoptosis.

PMID- 8990147
TI  - Goblet cell carcinoid arising in a mature teratoma of the mediastinum.
AB  - Goblet cell carcinoid (GCC) is a rare but distinctive neoplasm with features of
      both adenocarcinoma and carcinoid tumor. Most cases described in the literature
      have occurred in the appendix. An additional well-defined location is the ovary,
      and these tumors have been associated with a mature teratoma of the ovary. GCC
      arising within a mature teratoma of the mediastinum has not been described in the
      English-language literature. We report a case of this previously undescribed
      entity and provide a review of the literature on mediastinal teratomas with
      malignant transformation. The histologic findings included uniform, smooth
      bordered glandular nests lined by goblet cells and admixed endocrine and Paneth
      cells. Occasional tubular glands were present, as were transitional type glands
      with both goblet cell and tubular features. Cytologic atypia was minimal, and
      mitotic activity was rare. Immunohistochemical studies showed positive staining
      of GCC tumor cells with chromogranin, cytokeratin, neuron-specific enolase,
      serotonin (focal), and Leu-7 (focal). The GCC component was entirely contained
      within the mature teratoma.

PMID- 8990146
TI  - Composite pheochromocytoma/ganglioneuroma of the adrenal gland associated with
      multiple endocrine neoplasia 2A: case report with immunohistochemical analysis.
AB  - We report a case of composite pheochromocytoma/ganglioneuroma arising in a
      background of diffuse and nodular medullary hyperplasia in the adrenal gland of a
      34-year-old man with multiple endocrine neoplasia 2a (MEN 2a). Cells were
      histologically classified as chromaffin or chromaffin-like (small typical
      appearing pheochromocytoma cells), neuron-like (possessing ganglion cell
      morphology), and intermediate. We speculate that these cell types may represent a
      spectrum of differentiation of a neoplastic clone, with the intermediate cells
      representing a transitional stage between chromaffin cells and neurons. All three
      cell types in the composite tumor and all chromaffin cells in both nodular and
      nonnodular areas of the remaining medulla were strongly immunoreactive for
      tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. In
      contrast, neuron-like cells (and to a variable extent intermediate cells)
      displayed selective loss of expression of phenylethanolamine-N-methyltransferase
      (PNMT), the enzyme that synthesizes epinephrine. Proliferative activity of the
      composite tumor and both the nodular and nonnodular medulla was studied by
      staining for the endogenous cell proliferation antigen Ki-67, using monoclonal
      antibody MIB-1. MIB-1 labeling was highest in Schwann cell areas of the composite
      tumor, followed by chromaffin-like cells in the composite tumor and in the
      separate nodules. Labeling was absent in neuron-like cells, consistent with the
      cells' postulated status as terminally differentiated derivatives of a chromaffin
      cell precursor, and was highly variable in nonnodular areas of the medulla. The
      latter observation suggests topographical variation in signals that drive
      chromaffin cell proliferation in MEN.

PMID- 8990148
TI  - Peritoneal mesotheliomas.

PMID- 8990149
TI  - Signals and signs in the nervous system: the dynamic anatomy of electrical
      activity is probably information-rich.
AB  - The dichotomy between two groups of workers on neuroelectrical activity is
      retarding progress. To study the interrelations between neuronal unit spike
      activity and compound field potentials of cell populations is both unfashionable
      and technically challenging. Neither of the mutual disparagements is justified:
      that spikes are to higher functions as the alphabet is to Shakespeare and that
      slow field potentials are irrelevant epiphenomena. Spikes are not the basis of
      the neural code but of multiple codes that coexist with nonspike codes. Field
      potentials are mainly information-rich signs of underlying processes, but
      sometimes they are also signals for neighboring cells, that is, they exert
      influence. This paper concerns opportunities for new research with many channels
      of wide-band (spike and slow wave) recording. A wealth of structure in time and
      three-dimensional space is different at each scale-micro-, meso-, and
      macroactivity. The depth of our ignorance is emphasized to underline the
      opportunities for uncovering new principles. We cannot currently estimate the
      relative importance of spikes and synaptic communication vs. extrasynaptic graded
      signals. In spite of a preponderance of literature on the former, we must
      consider the latter as probably important. We are in a primitive stage of looking
      at the time series of wide-band voltages in the compound, local field, potentials
      and of choosing descriptors that discriminate appropriately among brain loci,
      states (functions), stages (ontogeny, senescence), and taxa (evolution). This is
      not surprising, since the brains in higher species are surely the most complex
      systems known. They must be the greatest reservoir of new discoveries in nature.
      The complexity should not deter us, but a dose of humility can stimulate the flow
      of imaginative juices.

PMID- 8990150
TI  - Dissecting intrinsic chaperonin activity.

PMID- 8990151
TI  - Cellular and molecular mechanics by atomic force microscopy: capturing the
      exocytotic fusion pore in vivo?

PMID- 8990152
TI  - Sunlight and skin cancer: another link revealed.

PMID- 8990153
TI  - RNA polymerase II transcription initiation: a structural view.
AB  - In eukaryotes, RNA polymerase II transcribes messenger RNAs and several small
      nuclear RNAs. Like RNA polymerases I and III, polymerase II cannot act alone.
      Instead, general initiation factors [transcription factor (TF) IIB, TFIID, TFIIE,
      TFIIF, and TFIIH] assemble on promoter DNA with polymerase II, creating a large
      multiprotein-DNA complex that supports accurate initiation. Another group of
      accessory factors, transcriptional activators and coactivators, regulate the rate
      of RNA synthesis from each gene in response to various developmental and
      environmental signals. Our current knowledge of this complex macromolecular
      machinery is reviewed in detail, with particular emphasis on insights gained from
      structural studies of transcription factors.

PMID- 8990154
TI  - Direct conversion of an oligopeptide from a beta-sheet to an alpha-helix: a model
      for amyloid formation.
AB  - A 16-amino acid oligopeptide forms a stable beta-sheet structure in water. In
      physiological solutions it is able to self-assemble to form a macroscopic matrix
      that stains with Congo red. On raising the temperature of the aqueous solution
      above 70 degrees C, an abrupt structural transition occurs in the CD spectra from
      a beta-sheet to a stable alpha-helix without a detectable random-coil
      intermediate. With cooling, it retained the alpha-helical form and took several
      weeks at room temperature to partially return to the beta-sheet form. Slow
      formation of the stable beta-sheet structure thus shows kinetic irreversibility.
      Such a formation of very stable beta-sheet structures is found in the amyloid of
      a number of neurological diseases. This oligopeptide could be a model system for
      studying the protein conformational changes that occurs in scrapie or Alzheimer
      disease. The abrupt and direct conversion from a beta-sheet to an alpha-helix may
      also be found in other processes, such as protein folding and protein-protein
      interaction. Furthermore, such drastic structure changes may also be exploited in
      biomaterials designed as sensors to detect environmental changes.

PMID- 8990157
TI  - A novel transporter involved in cobalt uptake.
AB  - Cobalt is an essential component of a low molecular-mass nitrile hydratase (L
      NHase) from Rhodococcus rhodochrous J1. We have found a new gene, nhlF, in the
      DNA region sandwiched between nhlBA encoding L-NHase and amdA encoding amidase,
      which are involved in the degradation of nitriles. The product of nhlF, NhlF,
      shows a significant sequence similarity with those of hoxN from Alcaligenes
      eutrophus, hupN from Bradyrhizobium japonicum, nixA from Helicobacter pylori, and
      ureH from Bacillus sp., which are considered to be involved in nickel uptake into
      these cells. Sequence and hydropathy plot analyses have shown that NhlF encodes a
      352-amino acid (aa) protein with eight hydrophobic putative membrane-spanning
      domains. nhlF expression in R. rhodochrous ATCC 12674 and Escherichia coli JM109
      confers uptake of 57Co in their cells, but not of 63Ni. The expression of both
      nhlF and nhlBA in R. rhodochrous ATCC 12674 exhibited higher NHase activity than
      nhlBA expression. These findings together with the inhibitory effect by
      uncouplers (CCCP and SF6847) for the cobalt uptake suggest that NhlF mediates the
      cobalt transport into the cell energy-dependently finally to provide L-NHase.

PMID- 8990158
TI  - A new pathway for vacuolar cadmium sequestration in Saccharomyces cerevisiae:
      YCF1-catalyzed transport of bis(glutathionato)cadmium.
AB  - The yeast cadmium factor (YCF1) gene encodes an MgATP-energized glutathione S
      conjugate transporter responsible for the vacuolar sequestration of organic
      compounds after their S-conjugation with glutathione. However, while YCF1 was
      originally isolated according to its ability to confer resistance to cadmium
      salts, neither its mode of interaction with Cd2+ nor the relationship between
      this process and organic glutathione-conjugate transport are known. Here we show
      through direct comparisons between vacuolar membrane vesicles purified from
      Saccharomyces cerevisiae strain DTY167, harboring a deletion of the YCF1 gene,
      and the isogenic wild-type strain DTY165 that YCF1 mediates the MgATP-energized
      vacuolar accumulation of Cd-glutathione complexes. The substrate requirements,
      kinetics and Cd2+/glutathione stoichiometry of cadmium uptake and the molecular
      weight of the transport-active complex demonstrate that YCF1 selectively
      catalyzes the transport of bis(glutathionato)cadmium (Cd x +GS2). On the basis of
      these results--the Cd2+ hypersensitivity of DTY167, versus DTY165, cells, the
      inducibility of YCF1-mediated transport, and the rapidity and spontaneity of Cd
      GS2 formation--this new pathway is concluded to contribute substantially to Cd2+
      detoxification.

PMID- 8990159
TI  - Spare the rod, spoil the regulation: necessity for a myosin rod.
AB  - Regulation of a variety of cellular contractile events requires that vertebrate
      smooth and non-muscle myosin II can achieve an "off" state. To examine the role
      of the myosin rod in this process, we determined the minimal size at which a
      myosin molecule is capable of regulation via light chain phosphorylation.
      Expressed smooth muscle myosin subfragments with as many as 100 amino acids of
      the coiled-coil rod sequence did not dimerize and were active independently of
      phosphorylation. To test whether dimerization per se restores regulation of
      ATPase activity, mutants were expressed with varying lengths of rod sequence,
      followed by C-terminal leucine zippers to stabilize the coiled-coil. Dimerization
      restored partial regulation, but the presence of a length of rod approximately
      equal to the myosin head was necessary to achieve a completely off state.
      Partially regulated short dimers could be converted into fully regulated
      molecules by addition of native rod sequence after the zipper. These results
      suggest that the myosin rod mediates specific interactions with the head that are
      required to obtain the completely inactive state of vertebrate smooth and non
      muscle myosins. If these interactions are prohibited under cellular conditions,
      unphosphorylated crossbridges can slowly cycle.

PMID- 8990160
TI  - The B12-dependent ribonucleotide reductase from the archaebacterium Thermoplasma
      acidophila: an evolutionary solution to the ribonucleotide reductase conundrum.
AB  - A coenzyme B12-dependent ribonucleotide reductase was purified from the
      archaebacterium Thermoplasma acidophila and partially sequenced. Using probes
      derived from the sequence, the corresponding gene was cloned, completely
      sequenced, and expressed in Escherichia coli. The deduced amino acid sequence
      shows that the catalytic domain of the B12-dependent enzyme from T. acidophila,
      some 400 amino acids, is related by common ancestry to the diferric tyrosine
      radical iron(III)-dependent ribonucleotide reductase from E. coli, yeast,
      mammalian viruses, and man. The critical cysteine residues in the catalytic
      domain that participate in the thiyl radical-dependent reaction have been
      conserved even though the cofactor that generates the radical is not.
      Evolutionary bridges created by the T. acidophila sequence and that of a B12
      dependent reductase from Mycobacterium tuberculosis establish homology between
      the Fe-dependent enzymes and the catalytic domain of the Lactobacillus
      leichmannii B12-dependent enzyme as well. These bridges are confirmed by a
      predicted secondary structure for the Lactobacillus enzyme. Sequence similarities
      show that the N-terminal domain of the T. acidophila ribonucleotide reductase is
      also homologous to the anaerobic ribonucleotide reductase from E. coli, which
      uses neither B12 nor Fe cofactors. A predicted secondary structure of the N
      terminal domain suggests that it is predominantly helical, as is the domain in
      the aerobic E. coli enzyme depending on Fe, extending the homologous family of
      proteins to include anaerobic ribonucleotide reductases, B12 ribonucleotide
      reductases, and Fe-dependent aerobic ribonucleotide reductases. A model for the
      evolution of the ribonucleotide reductase family is presented; in this model, the
      thiyl radical-based reaction mechanism is conserved, but the cofactor is chosen
      to best adapt the host organism to its environment. This analysis illustrates how
      secondary structure predictions can assist evolutionary analyses, each important
      in "post-genomic" biochemistry.

PMID- 8990161
TI  - From oligonucleotide shapes to genomic SELEX: novel biological regulatory loops.
AB  - The SELEX method and oligonucleotide combinatorial chemistry discovery process
      yields high-affinity/high-specificity ligands for virtually any molecular target.
      Typically, the enormous starting libraries used in the SELEX process contain
      10(14)-10(15) sequences. We now ask if the smaller sequences, complexity of
      extant organisms, and evolutionary history provide useful interactions between
      oligonucleotides and at least some unexpected targets. That is, do organisms
      contain a robust "linkage map" between their oligonucleotides and proteins and/or
      small molecules that enriches life?

PMID- 8990162
TI  - Folding of the N-terminal, ligand-binding region of integrin alpha-subunits into
      a beta-propeller domain.
AB  - The N-terminal approximately 440 aa of integrin alpha subunits contain seven
      sequence repeats. These are predicted here to fold into a beta-propeller domain.
      A homologous domain from the enzyme phosphatidylinositol phospholipase D is
      predicted to have the same fold. The domains contain seven four-stranded beta
      sheets arranged in a torus around a pseudosymmetry axis. The trimeric G-protein
      beta subunit (G beta) appears to be the most closely related beta-propeller.
      Integrin ligands and a putative Mg2+ ion are predicted to bind to the upper face
      of the beta-propeller. This face binds substrates in beta-propeller enzymes and
      is used by the G protein beta subunit to bind the G protein alpha subunit. The
      integrin alpha subunit I domain, which is structurally homologous to the G
      protein alpha subunit, is tethered to the top of the beta-propeller domain by a
      hinge that may allow movement of the domains relative to one another. The Ca2+
      binding motifs in integrin alpha subunits are on the lower face of the beta
      propeller.

PMID- 8990163
TI  - A computer screening approach to immunoglobulin superfamily structures and
      interactions: discovery of small non-peptidic CD4 inhibitors as novel
      immunotherapeutics.
AB  - The interaction between CD4 and major histocompatibility complex (MHC) class II
      proteins is critical for the activation of CD4+ T cells, which are involved in
      transplantation reactions and a number of autoimmune diseases. In this study we
      have identified a CD4 surface pocket as a functional epitope implicated in CD4
      MHC class II interaction and T-cell activation. A computer-based strategy has
      been used to screen approximately 150,000 non-peptidic organic compounds in a
      molecular data base and to identify a group of compounds as ligands of the
      proposed CD4 surface pocket. These small organic compounds have been shown to
      specifically block stable CD4-MHC class II binding, and exhibit significant
      inhibition of immune responses in animal models of autoimmune disease and
      allograft transplant rejection, suggesting their potential as novel
      immunosuppressants. This structure-based computer screening approach may have
      general implications for studying many immunoglobulin-like structures and
      interactions that share similar structural features. Furthermore, the results
      from this study have demonstrated that the rational design of small non-peptidic
      inhibitors of large protein-protein interfaces may indeed be an achievable goal.

PMID- 8990164
TI  - Accessibility of nuclear DNA to triplex-forming oligonucleotides: the integrated
      HIV-1 provirus as a target.
AB  - The control of gene transcription by antigene oligonucleotides rests upon the
      specific recognition of double-helical DNA by triplex-forming oligonucleotides.
      The development of the antigene strategy requires access to the targeted DNA
      sequence within the chromatin structure of the cell nucleus. In this sudy we have
      used HIV-1 chronically infected cells containing the HIV provirus as endogenous
      genes to demonstrate that the integrated HIV-1 proviral genome is accessible to
      triplex-forming oligonucleotides within cell nuclei. An oligonucleotide-psoralen
      conjugate targeted to the polypurine tract (PPT) of the HIV-1 proviral sequence
      was used as a tool to convert the noncovalent triple-helical complex into a
      covalent lesion on genomic DNA after UV irradiation of cells. Triplex-derived
      adducts were analyzed using two different methods. The photo-induced psoralen
      cross-link prevented cleavage of the target sequence by DraI restriction
      endonuclease, and the sequence-specific inhibition of cleavage was revealed and
      quantitated by Southern blot analysis. A quantitative analysis of cross-linking
      efficiency was also carried out by a competitive PCR-based assay. These two
      approaches allowed us to demonstrate that a triplex-forming oligonucleotide can
      recognize and bind specifically to a 15-bp sequence within the chromatin
      structure of cell nuclei.

PMID- 8990165
TI  - Drosophila TAF(II)230 and the transcriptional activator VP16 bind competitively
      to the TATA box-binding domain of the TATA box-binding protein.
AB  - The transcription initiation factor TFIID, consisting of the TATA box-binding
      protein (TBP) and many TBP-associated factors (TAFs), plays a central role in
      both basal and activated transcription. An intriguing finding is that the 80
      residue N-terminal region of Drosophila TAF(II)230 [dTAF(II)230-(2-81)] can bind
      directly to TBP and inhibit its function. Here, studies with mutated forms of TBP
      demonstrate that dTAF(II)230-(2-81) binds to the concave surface of TBP, which is
      important for TATA box binding. Previously, it was reported that a point mutation
      (L114K) on this concave surface destroys the ability of TBP to bind VP16 and to
      mediate VP16-dependent activation in vitro, but has no effect on basal
      transcription. Importantly, the same TBP mutation eliminates TBP binding to
      dTAF(II)230-(2-81). Consistent with these effects of the L114K mutation,
      dTAF(II)230-(2-81) and the VP16 activation domain compete for binding to wild
      type TBP. These results indicate that transcriptional regulation may involve, in
      part, competitive interactions between transcriptional activators and TAFs on the
      TBP surface.

PMID- 8990166
TI  - The motor domain and the regulatory domain of myosin solely dictate enzymatic
      activity and phosphorylation-dependent regulation, respectively.
AB  - While the structures of skeletal and smooth muscle myosins are homologous, they
      differ functionally from each other in several respects, i.e., motor activities
      and regulation. To investigate the molecular basis for these differences, we have
      produced a skeletal/smooth chimeric myosin molecule and analyzed the motor
      activities and regulation of this myosin. The produced chimeric myosin is
      composed of the globular motor domain of skeletal muscle myosin (Met1-Gly773) and
      the C-terminal long alpha-helix domain of myosin subfragment 1 as well as myosin
      subfragment 2 (Gly773-Ser1104) and light chains of smooth muscle myosin. Both the
      actin-activated ATPase activity and the actin-translocating activity of the
      chimeric myosin were completely regulated by light chain phosphorylation. On the
      other hand, the maximum actin-activated ATPase activity of the chimeric myosin
      was the same as skeletal myosin and thus much higher than smooth myosin. These
      results show that the C-terminal light chain-associated domain of myosin head
      solely confers regulation by light chain phosphorylation, whereas the motor
      domain determines the rate of ATP hydrolysis. This is the first report, to our
      knowledge, that directly determines the function of the two structurally
      separated domains in myosin head.

PMID- 8990167
TI  - The molecular chaperone hsp40 regulates the activity of P58IPK, the cellular
      inhibitor of PKR.
AB  - The interferon-induced double-stranded RNA-activated protein kinase, PKR, likely
      contributes to both the antiviral and the antiproliferative effects of
      interferon. We previously found that influenza virus avoids the translational
      inhibitory effects of activated PKR by activating a cellular inhibitory protein,
      termed P58IPK, based on its Mr of 58,000. P58IPK is a member of the
      tetratricopeptide family of proteins and possesses significant homology to the
      conserved J region of the DnaJ family of heat shock proteins. We earlier
      hypothesized that P58IPK was kept in an inactive state with its own inhibitor
      (termed I-P58IPK) in uninfected cells. We therefore attempted the purification
      and characterization of I-P58IPK. The following data suggest that we have
      identified the molecular chaperone, hsp40, as 1-P58IPK. (i) The MonoP-purified I
      P58IPK protein reacted with hsp40 antibody. (ii) This preparation demonstrated
      high specific activity in an in vitro functional assay containing only purified
      recombinant and native components. (iii) Purified, recombinant hsp40 protein
      inhibited P58IPK in an identical in vitro assay. (iv) Finally, we demonstrate
      that hsp40 directly complexes with P58IPK, in vitro, suggesting the inhibition
      occurs through a direct interaction. Our data, taken together, provide evidence
      for a novel intersection between the heat shock and interferon pathways, and
      suggest that influenza virus regulates PKR activity through the recruitment of a
      cellular stress pathway.

PMID- 8990168
TI  - Interferon gamma-induced transcription of the murine ISGF3gamma (p48) gene is
      mediated by novel factors.
AB  - In this investigation, we show that the gene encoding p48, a subunit of
      transcription factor ISGF3, is transcriptionally induced by interferon gamma (IFN
      gamma). We have identified a novel IFN-gamma-activated response element in the
      p48 gene promoter. This motif, notated as gamma-activated transcriptional element
      (GATE), has no significant resemblance to either pIRE (palindromic IFN-response
      element) or GAS (the IFN-gamma-activated sequence) but has partial homology to
      ISRE (IFN-stimulated response element). When fused to a neutral promoter, GATE, a
      24-bp element, induced the expression of reporter genes following IFN-gamma
      treatment. In murine RAW cells, two IFN-gamma-inducible factors (GIF) bind to
      GATE. Binding of these factors to GATE is inhibited by cycloheximide and
      staurosporine. Although p48 gene induction is dependent on STAT1 and JAK1,
      activated STAT1 does not bind to GATE. Thus, GIFs appear to be novel trans-acting
      factors in the IFN-signaling pathway.

PMID- 8990169
TI  - Cloning and characterization of a functional human homolog of Escherichia coli
      endonuclease III.
AB  - Repair of oxidative damage to DNA bases is essential to prevent mutations and
      cell death. Endonuclease III is the major DNA glycosylase activity in Escherichia
      coli that catalyzes the excision of pyrimidines damaged by ring opening or ring
      saturation, and it also possesses an associated lyase activity that incises the
      DNA backbone adjacent to apurinic/apyrimidinic sites. During analysis of the area
      adjacent to the human tuberous sclerosis gene (TSC2) in chromosome region
      16p13.3, we identified a gene, OCTS3, that encodes a 1-kb transcript. Analysis of
      OCTS3 cDNA clones revealed an open reading frame encoding a predicted protein of
      34.3 kDa that shares extensive sequence similarity with E. coli endonuclease III
      and a related enzyme from Schizosaccharomyces pombe, including a conserved active
      site region and an iron/sulfur domain. The product of the OCTS3 gene was
      therefore designated hNTH1 (human endonuclease III homolog 1). The hNTH1 protein
      was overexpressed in E. coli and purified to apparent homogeneity. The
      recombinant protein had spectral properties indicative of the presence of an
      iron/sulfur cluster, and exhibited DNA glycosylase activity on double-stranded
      polydeoxyribonucleotides containing urea and thymine glycol residues, as well as
      an apurinic/apyrimidinic lyase activity. Our data indicate that hNTH1 is a
      structural and functional homolog of E. coli endonuclease III, and that this
      class of enzymes, for repair of oxidatively damaged pyrimidines in DNA, is highly
      conserved in evolution from microorganisms to human cells.

PMID- 8990170
TI  - In vivo analysis of the functional domains of the Drosophila splicing regulator
      RBP1.
AB  - The Drosophila splicing factor RBP1 participates together with TRA and TRA-2 in
      the regulation of alternative splicing of doublesex (dsx) pre-mRNA. It does so by
      recognizing RBP1 RNA target sequences in the dsx pre-mRNA. RBP1 belongs to the
      Ser-Arg-rich (SR) protein family of splicing factors, which have in common a N
      terminal RNA recognition motif-type RNA binding domain, a Gly-rich region, and a
      C-terminal SR domain. Using a tissue culture transfection assay, we demonstrate
      that the Gly residues within the Gly-rich domain, the ribonucleoprotein motifs
      within the RNA recognition motif RNA binding domain, and the SR domain are
      required for regulation of dsx splicing by RBP1 in vivo. Furthermore, using a two
      hybrid system, we show protein-protein interactions between RBP1 and itself and
      between RBP1 and TRA-2. The SR domain and the Gly residues within the Gly-rich
      domain of RBP1 were found to be involved in these protein-protein interactions.
      Our results suggest that RBP1 and TRA-2 function in regulation of dsx splicing by
      forming a complex.

PMID- 8990171
TI  - YY1 regulates vitamin D receptor/retinoid X receptor mediated transactivation of
      the vitamin D responsive osteocalcin gene.
AB  - The responsiveness of genes to steroid hormones is principally mediated by
      functional interactions between DNA-bound hormone receptors and components of the
      transcriptional initiation machinery, including TATA-binding protein, TFIIB, or
      other RNA polymerase II associated factors. This interaction can be
      physiologically modulated by promoter context-specific transcription factors to
      facilitate optimal responsiveness of gene expression to hormone stimulation. One
      postulated regulatory mechanism involves the functional antagonism between
      hormone receptors and nonreceptor transcription factors interacting at the same
      hormone response element. Here we demonstrate that the multifunctional regulator
      YY1 represses 1,25-dihydroxyvitamin D3 (vitamin D)-induced transactivation of the
      bone tissue-specific osteocalcin gene. We identify YY1 recognition sequences
      within the vitamin D response element (VDRE) of the osteocalcin gene that are
      critical for YY1-dependent repression of vitamin D-enhanced promoter activity. We
      show that YY1 and vitamin D receptor (VDR)/retinoid X receptor heterodimers
      compete for binding at the osteocalcin VDRE. In addition, we find that YY1
      interacts directly with TFIIB, and that one of the two tandemly repeated
      polypeptide regions of TFIIB spanning the basic domain is responsible for this
      interaction. TFIIB and VDR can also interact directly, and these factors
      synergize to mediate transactivation. Our results suggest that YY1 regulates
      vitamin D enhancement of osteocalcin gene transcription in vivo by interfering
      with the interactions of the VDR with both the VDRE and TFIIB.

PMID- 8990172
TI  - PU.1 can participate in an active enhancer complex without its transcriptional
      activation domain.
AB  - The transcription factor PU.1 is necessary for the development of multiple
      hematopoietic lineages and contributes to the activity of the immunoglobulin
      kappa 3' enhancer. A variety of proteins bind to the 3' enhancer (PU.1, PIP,
      ATF1, CREM, c-Fos, c-Jun, and E2A), but the mechanism of 3'-enhancer activity and
      the proteins necessary for its activity are presently unclear. We show here that
      PU.1 participates with other transcription factors in forming a higher-order
      complex with 3'-enhancer DNA sequences. Each protein is necessary for formation
      of this complex. Individually, transcription factors that bind to the 3' enhancer
      do not appreciably stimulate transcription in a cell type in which the 3'
      enhancer is normally silent (NIH 3T3). However, mixture of multiple transcription
      factors (PU.1, PIP, c-Fos, and c-Jun) can greatly activate the enhancer. PU.1 is
      necessary for maximal enhancer activity, but mutants of PU.1 that lack the
      transcriptional activation domain are nearly as efficient at stimulating enhancer
      activity as the wild-type PU.1 protein. PU.1 apparently can activate
      transcription by playing an architectural role in interactions with other
      transcription factors.

PMID- 8990173
TI  - SC35-mediated reconstitution of splicing in U2AF-depleted nuclear extract.
AB  - Assembly of the mammalian spliceosome is known to proceed in an ordered fashion
      through several discrete complexes, but the mechanism of this assembly process
      may not be universal. In an early step, pre-mRNAs are committed to the splicing
      pathway through association with U1 small nuclear ribonucleoprotein (snRNP) and
      non-snRNP splicing factors, including U2AF and members of the SR protein family.
      As a means of studying the steps of spliceosome assembly, we have prepared HeLa
      nuclear extracts specifically depleted of the splicing factor U2AF. Surprisingly,
      the SR protein SC35 can functionally substitute for U2AF65 in the reconstitution
      of pre-mRNA splicing in U2AF-depleted extracts. This reconstitution is substrate
      specific and is reminiscent of the SC35-mediated reconstitution of splicing in
      extracts depleted of U1 snRNP. However, SC35 reconstitution of splicing in U2AF
      depleted extracts is dependent on the presence of functional U1 snRNP. These
      observations suggest that there are at least three distinguishable mechanisms for
      the binding of U2 snRNP to the pre-mRNA, including U2AF-dependent and 
      independent pathways.

PMID- 8990174
TI  - Ligand-induced overexpression of a constitutively active beta2-adrenergic
      receptor: pharmacological creation of a phenotype in transgenic mice.
AB  - Transgenic overexpression (40- to 100-fold) of the wild-type human beta2
      adrenergic receptor in the hearts of mice leads to a marked increase in cardiac
      contractility, which is apparently due to the low level of spontaneous (i.e.,
      agonist-independent) activity inherent in the receptor. Here we report that
      transgenic mice expressing a mutated constitutively active form of the receptor
      (CAM) show no such phenotype, owing to its modest expression (3-fold above
      endogenous cardiac beta-adrenergic receptor levels). Surprisingly, treatment of
      the animals with a variety of beta-adrenergic receptor ligands leads to a 50-fold
      increase in CAM beta2-adrenergic receptor expression, by stabilizing the CAM
      beta2-adrenergic receptor protein. Receptor up-regulation leads in turn to marked
      increases in adenylate cyclase activity, atrial tension determined in vitro, and
      indices of cardiac contractility determined in vivo. These results illustrate a
      novel mechanism for regulating physiological responses, i.e., ligand-induced
      stabilization of a constitutively active but inherently unstable protein.

PMID- 8990176
TI  - Two-state models of protein folding kinetics.
AB  - The folding of some proteins appears to be a two-state kinetic process. A two
      state kinetic model is justified if protein molecules rapidly equilibrate between
      different unfolded conformations prior to complete folding. Here I show that this
      rapid equilibration is a natural consequence of reasonable assumptions about
      reaction rate constants and folding thermodynamics.

PMID- 8990175
TI  - A human protein related to yeast Cdc6p.
AB  - The unstable proteins Cdc6p and cdc18+ are essential and rate limiting for the
      initiation of DNA replication in Saccharomyces cerevisiae and Schizosaccharomyces
      pombe, respectively, and also participate in checkpoint controls that ensure DNA
      replication is completed before mitosis is initiated. We have identified Xenopus
      and human proteins closely related to Cdc6p/cdc18. The human protein, p62(cdc6),
      is encoded on chromosome 17q21.3 and includes putative cyclin-dependent kinase
      phosphorylation sites, destruction boxes, a nucleotide binding/ATPase domain, and
      a potential leucine zipper. Expression of p62(cdc6) mRNA and protein is
      suppressed in human diploid fibroblasts made quiescent by serum starvation, and
      peaks as cells reenter the cell cycle and replicate DNA following serum
      stimulation. Conservation of structure among proteins involved in initiation
      suggests that fundamental features of replication complexes are maintained in all
      eukaryotes.

PMID- 8990177
TI  - Expression of p24, a novel p21Waf1/Cip1/Sdi1-related protein, correlates with
      measurement of the finite proliferative potential of rodent embryo fibroblasts.
AB  - Normal mammalian fibroblasts undergo a limited number of divisions when cultured
      in vitro before entering a state of replicative senescence. The molecular basis
      for the determination of the finite mitotic potential is not known. Nevertheless,
      simian virus 40 T antigen, among other oncogenes, is able to prevent senescence
      in rodent embryo fibroblasts. T antigen immortalized cells are dependent upon
      this protein for maintaining growth once their normal mitotic life span has
      elapsed. Even though the mechanism that measures the finite mitotic potential of
      rodent fibroblasts is not known, it has been shown that it continues to function
      normally in the presence of this immortalizing gene. Accumulation of cyclin
      dependent kinase inhibitors such as p21Waf1/Cip1/Sdi1 could potentially be a
      component of the mechanism that determines the finite life span. Here we show
      that accumulation of p21Waf1/Cip1/Sdi1 does not correlate with this biological
      counting mechanism, but we have identified p24, a p21Waf1/Cip1/Sdi1-related
      protein, whose accumulation does correlate with the measurement of the finite
      proliferative potential of rodent embryo fibroblasts and suggest that
      sequestration might be a mechanism by which its activity is regulated.

PMID- 8990179
TI  - A cellular 65-kDa protein recognizes the negative regulatory element of human
      papillomavirus late mRNA.
AB  - Papillomavirus late gene expression is tightly linked to the differentiation
      state of the host cell. Levels of late mRNAs are only in part controlled by
      regulation of the late promoter, other posttranscriptional mechanisms exist that
      reduce the amount of late mRNA in undifferentiated cells. Previously we described
      a negative regulatory element (NRE) located upstream of the human papillomavirus
      type 16 late poly(A) site. We have delineated the NRE to a 79-nt region in which
      a G+U-rich region was the major determinant of NRE activity. UV-crosslinking
      assays identified a prominent nuclear protein of 65 kDa as the only factor in
      close contact with the NRE, and a complex of at least five proteins, including
      the 65-kDa protein, was enriched on NRE-RNA. Binding of the 65-kDa protein was
      depleted by preincubation with poly(U) Sepharose in high salt, a property
      characteristic of the U2 small nuclear ribonucleoprotein auxiliary factor U2AF65
      and bacterially expressed U2AF65 exhibited NRE binding. The 65-kDa protein bound
      to the G+U-rich NRE 3' half which shows homology to the B2P2 sequence a known
      U2AF65 binding site in the alpha-tropomyosin gene, and the G+U-rich element can
      be replaced by B2P2 in the binding assay. Treatment of cells with phorbol 12
      myristate 13-acetate reduced binding of the 65-kDa protein, induced NRE binding
      of a cytoplasmic protein, and relieved the NRE block on reporter gene expression.

PMID- 8990178
TI  - Resistance of actin to cleavage during apoptosis.
AB  - A small number of cellular proteins present in the nucleus, cytosol, and membrane
      fraction are specifically cleaved by the interleukin-1beta-converting enzyme
      (ICE)-like family of proteases during apoptosis. Previous results have
      demonstrated that one of these, the cytoskeletal protein actin, is degraded in
      rat PC12 pheochromocytoma cells upon serum withdrawal. Extracts from etoposide
      treated U937 cells are also capable of cleaving actin. It was assumed that
      cleavage of actin represented a general phenomenon, and a mechanism coordinating
      proteolytic, endonucleolytic, and morphological aspects of apoptosis was
      proposed. We demonstrate here that actin is resistant to degradation in several
      different human cells induced to undergo apoptosis in response to a variety of
      stimuli, including Fas ligation, serum withdrawal, cytotoxic T-cell killing, and
      DNA damage. On the other hand, cell-free extracts from these cells and the ICE
      like protease CPP32 were capable of cleaving actin in vitro. We conclude that
      while actin contains cleavage sites for ICE-like proteases, it is not degraded in
      vivo in human cells either because of lack of access of these proteases to actin
      or due to the presence of other factors that prevent degradation.

PMID- 8990180
TI  - Mutation of gene-proximal regulatory elements disrupts human epsilon-, gamma-,
      and beta-globin expression in yeast artificial chromosome transgenic mice.
AB  - Previous studies have defined transcriptional control elements, in addition to
      the promoters, that both lie near individual human beta-globin locus genes and
      have been implicated in their differential stage-specific regulation during
      development (i.e., are believed to directly participate in hemoglobin switching).
      We have reinvestigated the activities during erythropoiesis that might be
      conferred by two of the more intensively analyzed of these elements, the epsilon
      globin gene 5' silencer and the beta-globin gene 3' enhancer, by deleting them
      from a yeast artificial chromosome that spans the human beta-globin locus, and
      then analyzing transgenic mice for expression of all of the human genes. These
      studies show that sequences within the epsilon-globin "silencer" are not only
      required for silencing but are also required for activation of epsilon-globin
      transcription; furthermore, deletion of the silencer simultaneously reduced gamma
      globin transcription during the yolk sac stage of erythroid development. Analysis
      of the adult beta-globin gene 3' enhancer deletion showed that its deletion
      affects only that gene.

PMID- 8990181
TI  - Effects of population and affluence on CO2 emissions.
AB  - We developed a stochastic version of the Impact = Population x Affluence x
      Technology (IPAT) model to estimate the effects of population, affluence, and
      technology on national CO2 emissions. Our results suggest that, for population,
      there are diseconomies of scale for the largest nations that are not consistent
      with the assumption of direct proportionality (log-linear effects) common to most
      previous research. In contrast, the effects of affluence on CO2 emissions appear
      to reach a maximum at about $10,000 in per- capita gross domestic product and to
      decline at higher levels of affluence. These results confirm the general value of
      the IPAT model as a starting point for understanding the anthropogenic driving
      forces of global change and suggest that population and economic growth
      anticipated over the next decade will exacerbate greenhouse gas emissions.

PMID- 8990183
TI  - Increased competitiveness of nematode sperm bearing the male X chromosome.
AB  - Male offspring, which cannot reproduce independently, represent a cost of sexual
      reproduction. This cost is eliminated by the production of hermaphroditic
      offspring in the self-fertilizing nematode Caenorhabditis briggsae. However,
      these hermaphrodites can outcross by mating with males. Half the sperm received
      from males contain no sex chromosome and therefore give rise to male progeny.
      Mating with males should thus impose the cost of making male offspring. We found
      that male sperm took immediate precedence over hermaphrodite sperm, resulting in
      maximized outcrossing, but the appearance of male progeny was delayed after
      mating. This delay is caused by the male X-bearing sperm outcompeting their nullo
      X counterparts. The competitive advantage of X-bearing sperm over nullo-X sperm
      is limited to sperm from males; it did not occur in a mutant hermaphrodite that
      produces both types of sperm. The chromosomal effect on sperm competitiveness in
      C. briggsae, which has not been observed in other species, suggests that the X
      chromosome has evolved a form of meiotic drive, selfishly increasing the
      competitiveness of sperm that bear it over those that do not. Thus, the multiple
      levels of sperm competitiveness found in C. briggsae maximize outcrossing after
      mating while delaying the cost of making male offspring.

PMID- 8990184
TI  - A multipurpose transposon system for analyzing protein production, localization,
      and function in Saccharomyces cerevisiae.
AB  - Analysis of the function of a particular gene product typically involves
      determining the expression profile of the gene, the subcellular location of the
      protein, and the phenotype of a null strain lacking the protein. Conditional
      alleles of the gene are often created as an additional tool. We have developed a
      multifunctional, transposon-based system that simultaneously generates constructs
      for all the above analyses and is suitable for mutagenesis of any given
      Saccharomyces cerevisiae gene. Depending on the transposon used, the yeast gene
      is fused to a coding region for beta-galactosidase or green fluorescent protein.
      Gene expression can therefore be monitored by chemical or fluorescence assays.
      The transposons create insertion mutations in the target gene, allowing
      phenotypic analysis. The transposon can be reduced by cre-lox site-specific
      recombination to a smaller element that leaves an epitope tag inserted in the
      encoded protein. In addition to its utility for a variety of immunodetection
      purposes, the epitope tag element also has the potential to create conditional
      alleles of the target gene. We demonstrate these features of the transposons by
      mutagenesis of the SPA2, ARP100, SER1, and BDF1 genes.

PMID- 8990185
TI  - Penelope, a new family of transposable elements and its possible role in hybrid
      dysgenesis in Drosophila virilis.
AB  - A hybrid dysgenesis syndrome occurs in Drosophila virilis when males from an
      established laboratory strain are crossed to females obtained from the wild,
      causing the simultaneous mobilization of several different transposable elements.
      The insertion sequence responsible for the mutant phenotype of a dysgenic yellow
      allele has been characterized and named Penelope. In situ hybridization and
      Southern analyses reveal the presence of more than 30 copies of this element in
      the P-like parental strain, whereas Penelope is absent in all M-like strains
      tested. Penelope contains one 2.5-kb-long ORF that could encode products with
      homology to integrase and reverse transcriptase. Northern analysis and whole
      mount in situ hybridization show strong induction of a 2.6-kb RNA in the ovaries
      of dysgenic females that is expressed at very low levels in the parental strains
      or in the progeny from the reciprocal cross. Injection of Penelope-containing
      plasmids into preblastoderm embryos of an M-like strain results in mutant progeny
      caused by insertion of Ulysses and perhaps other transposons, suggesting that
      Penelope expression might be responsible for the observed dysgenesis syndrome and
      the simultaneous mobilization of other transposable elements.

PMID- 8990186
TI  - Conversion of inactive glycosylation inhibiting factor to bioactive derivatives
      by modification of a SH group.
AB  - Escherichia coli-derived recombinant human glycosylation inhibiting factor
      (rhGIF) contains three cysteine residues (Cys-57, -60, and -81). All SH groups in
      the cysteine residues are free, and the GIF molecule had no biologic activity.
      Carboxymethylation of the SH group of Cys-60 in the molecule resulted in the
      generation of bioactivity, although the activity of the carboxymethylated GIF was
      10- to 20-fold less than that of suppressor T cell (Ts)-derived GIF. However,
      treatment of the inactive rhGIF with ethylmercurithiosalicylate or 5,5'
      dithiobis(2-nitrobenzoic acid) (DTNB) resulted in the generation of derivatives
      whose bioactivity was comparable to that of the Ts-derived bioactive GIF. The
      activity of these derivatives was lost by treatment with DTT. Isolation and
      chemical analysis of the DTNB-treated GIF derivative revealed that binding the 5
      thio-2-nitrobenzoic acid group with Cys-60 was responsible for the generation of
      the highly bioactive derivative. Inactive cytosolic GIF from mammalian cells
      could also be converted to bioactive derivative by treatment with the SH reagent,
      while Ts-derived bioactive GIF was inactivated by DTT. These results, together
      with an x-ray crystal structure of GIF molecules, strongly suggest that the
      generation of bioactivity of GIF in Ts cells is due to posttranslational
      modifications that result in conformational changes in the molecule.

PMID- 8990187
TI  - Memory B lymphocytes migrate to bone marrow in humans.
AB  - IgM-bearing B lymphocytes with mature phenotype (CD10- CD24(lo) IgD+) are
      acquired after birth in the bone marrow of humans. These B cells are defined here
      as relatively large, nondividing lymphocytes, variable proportions of which
      express cell surface molecules indicative of relatively recent activation.
      Analysis of V(H)5(2) (heavy chain variable region) gene transcripts indicated
      point mutations throughout the Ig variable region from the mature IgM+ B
      population but not from the immature B cells in the bone marrow. The mutations
      were concentrated in the complementarity determining regions, and amino acid
      substitutions were favored over silent mutations, findings indicative of antigen
      selection within germinal centers in peripheral lymphoid tissues. The V(H)
      sequence analysis also revealed the existence of clonal relatives in individual
      bone marrow samples. These antigen-experienced lymphocytes did not secrete Ig
      spontaneously but could be induced to do so in vitro. The data suggest that a
      subpopulation of memory B lymphocytes generated during antigen responses
      recirculates to the bone marrow in humans.

PMID- 8990188
TI  - Beta cell apoptosis in T cell-mediated autoimmune diabetes.
AB  - Insulin-dependent diabetes mellitus results from T cell-mediated destruction of
      insulin-producing, pancreatic islet beta cells. How this destruction takes place
      has remained elusive--largely due to the slow kinetics of disease progression. By
      crossing a transgenic mouse carrying a beta cell-specific T cell receptor onto
      the NOD.scid background, we produced a simplified but robust and accelerated
      model of diabetes. This mouse produces CD4+ T cells bearing transgenic T cell
      receptor but is devoid of CD8+ T cells and B cells. More importantly, this mouse
      develops a rapid diabetes, which has allowed us to record and quantify beta cell
      death. We have determined that beta cells within the inflamed islets die by
      apoptosis.

PMID- 8990189
TI  - Transgenic studies with a keratin promoter-driven growth hormone transgene:
      prospects for gene therapy.
AB  - Keratinocytes are potentially appealing vehicles for the delivery of secreted
      gene products because they can be transferred to human skin by the relatively
      simple procedure of grafting. Adult human keratinocytes can be efficiently
      propagated in culture with sufficient proliferative capacity to produce enough
      epidermis to cover the body surface of an average adult. However, the feasibility
      of delivering secreted proteins through skin grafting rests upon (i) the strength
      of the promoter in keratinocytes and (ii) the efficiency of protein transport
      through the basement membrane of the stratified epithelium and into the
      bloodstream. In this paper, we use transgenic technology to demonstrate that the
      activity of the human keratin 14 promoter remains high in adult skin and that
      keratinocyte-derived human growth hormone (hGH) can be produced, secreted, and
      transported to the bloodstream of mice with efficiency that is sufficient to
      exceed by an order of magnitude the circulating hGH concentration in growing
      children. Transgenic skin grafts from these adults continue to produce and
      secrete hGH stably, at approximately 1/10 physiological levels in the bloodstream
      of nontransgenic recipient mice. These studies underscore the utility of the
      keratin 14 promoter for expressing foreign transgenes in keratinocytes and
      demonstrate that keratinocytes can be used as effective vehicles for transporting
      factors to the bloodstream and for eliciting metabolic changes. These findings
      have important implications for considering the keratinocyte as a possible
      vehicle for gene therapy.

PMID- 8990190
TI  - Interleukin (IL) 1beta, IL-1 receptor antagonist, IL-10, and IL-13 gene
      expression in the central nervous system and anterior pituitary during systemic
      inflammation: pathophysiological implications.
AB  - The pathophysiology of systemic inflammation and sepsis involves peripheral
      organs, causing gastrointestinal, renal, and cardiovascular alterations, as well
      as the central nervous system (CNS), affecting sleep, temperature regulation,
      behavior, and neuroendocrine function. The molecular basis of the CNS effects of
      systemic inflammation are not fully elucidated. Here we show that the CNS
      responds to systemic inflammation with pronounced IL-1beta gene expression and
      limited IL-1 receptor antagonist (IL-1ra), IL-10, and IL-13 gene expression. This
      pattern occurs throughout the CNS, including areas such as the subfornical organ,
      pineal gland, neurohypophysis, and hypothalamus. In contrast, in the anterior
      pituitary, we found limited IL-1beta gene expression but marked induction of the
      mRNA encoding for the secreted isoform of IL-1ra, secreted IL-1ra. We conclude
      that the central manifestations of peripheral inflammation are mediated by
      endogenous brain IL-1beta synthesized during systemic inflammation in the context
      of limited central cytokine counter regulation of IL-1. As IL-1beta is a potent
      stimulus for inducible nitric oxide synthase expression and activity, these
      findings explain our previous observation that systemic inflammation promotes
      inducible nitric oxide synthase gene expression in the brain and the spillover of
      NO metabolites into cerebrospinal fluid. The CNS transcription of the HIV-1
      replication factor IL-1beta in the context of limited transcription of the IL-1
      replication inhibitors IL-1ra, IL-10, and IL-13 might help explain the negative
      impact of systemic inflammation on the clinical course of AIDS. In addition, we
      propose that IL-1ra may be secreted by the anterior pituitary as a systemic anti
      inflammatory hormone that is released in response to IL-1beta originated from
      multiple sources.

PMID- 8990191
TI  - Sialadenitis histologically resembling Sjogren syndrome in mice transgenic for
      hepatitis C virus envelope genes.
AB  - Hepatitis C virus (HCV), a major causative agent of non-A, non-B chronic
      hepatitis, is also suggested to be associated with extrahepatic manifestations
      such as mixed cryoglobulinemia and glomerulonephritis. Two independent lines of
      transgenic mice carrying the HCV envelope genes have been shown previously to
      express the HCV envelope proteins in organs, including the liver and salivary
      glands, which results in no pathological changes in the liver. Further analysis
      of these animals now has revealed that they develop an exocrinopathy involving
      the salivary and lachrymal glands. This pathology resembles Sjogren syndrome,
      which also is suggested to have a possible association with chronic hepatitis C.
      These observations suggest that HCV might be involved in the pathogenesis of
      sialadenitis in humans and that this transgenic mouse system would be a good
      animal model for the study of HCV infection.

PMID- 8990192
TI  - Terminal differentiation of human liposarcoma cells induced by ligands for
      peroxisome proliferator-activated receptor gamma and the retinoid X receptor.
AB  - Induction of terminal differentiation represents a promising therapeutic approach
      to certain human malignancies. The peroxisome proliferator-activated receptor
      gamma (PPAR gamma) and the retinoid X receptor alpha (RXR alpha) form a
      heterodimeric complex that functions as a central regulator of adipocyte
      differentiation. Natural and synthetic ligands for both receptors have been
      identified. We demonstrate here that PPAR gamma is expressed at high levels in
      each of the major histologic types of human liposarcoma. Moreover, primary human
      liposarcoma cells can be induced to undergo terminal differentiation by treatment
      with the PPAR gamma ligand pioglitazone, suggesting that the differentiation
      block in these cells can be overcome by maximal activation of the PPAR pathway.
      We further demonstrate that RXR-specific ligands are also potent adipogenic
      agents in cells expressing the PPAR gamma/RXR alpha heterodimer, and that
      simultaneous treatment of liposarcoma cells with both PPAR gamma- and RXR
      specific ligands results in an additive stimulation of differentiation.
      Liposarcoma cell differentiation is characterized by accumulation of
      intracellular lipid, induction of adipocyte-specific genes, and withdrawal from
      the cell cycle. These results suggest that PPAR gamma ligands such as
      thiazolidinediones and RXR-specific retinoids may be useful therapeutic agents
      for the treatment of liposarcoma.

PMID- 8990193
TI  - A Drosophila homolog of the tumor suppressor gene adenomatous polyposis coli down
      regulates beta-catenin but its zygotic expression is not essential for the
      regulation of Armadillo.
AB  - Mutations in the adenomatous polyposis coli gene (which encodes a protein called
      APC) are associated with the formation of intestinal polyps and colon cancers. To
      facilitate the functional study of APC we have isolated its Drosophila homolog (D
      APC) by screening an expression library with an antibody against human APC. The
      isolated cDNA encodes a predicted 2416-amino acid protein containing significant
      homology to multiple domains of mammalian APCs. D-APC has seven complete
      armadillo repeats with 60% identity to its human homolog, one beta-catenin
      binding site, and up to 7 copies of a 20-amino acid repeat with the average of
      50% identity to human APC at amino acid level. D-APC, like its human counterpart,
      also contains a basic domain. Expression of the domain of D-APC homologous to the
      region required for beta-catenin down-regulation resulted in down-regulation of
      intracellular beta-catenin in a mammalian cell line. This same region bound to
      the Armadillo (Arm) protein, in vitro, the Drosophila homolog of beta-catenin. D
      APC RNA and protein expression is very low, if detectable at all, during stages
      when Arm protein accumulates in a striped pattern in the epidermis of the
      Drosophila embryos. Removing zygotic D-APC expression did not alter Arm protein
      distribution, and the final cuticle pattern was not affected significantly. As
      observed in the rodent, high levels of D-APC expression have been detected in the
      central nervous system, suggesting a role for D-APC in central nervous system
      formation.

PMID- 8990194
TI  - A natural transactivation mutation in the thyroid hormone beta receptor: impaired
      interaction with putative transcriptional mediators.
AB  - The syndrome of resistance to thyroid hormone is characterized by elevated serum
      free thyroid hormones, failure to suppress pituitary thyrotropin secretion, and
      variable peripheral refractoriness to hormone action. Here we describe a novel
      leucine to valine mutation in codon 454 (L454V) of the thyroid hormone beta
      receptor (TR beta) in this disorder, resulting in a mutant receptor with unusual
      functional properties. Although the mutant protein binds ligand comparably to
      wild-type receptor and forms homo- and heterodimers on direct repeat, everted
      repeat, or palindromic thyroid response elements, its ability to activate
      transcription via these elements is markedly impaired. The hydrophobic leucine
      residue lies within an amphipathic alpha-helix at the carboxyl terminus of TR
      beta and the position of the homologous residue in the crystal structure of TR
      alpha indicates that its side chain is solvent-exposed and might interact with
      other proteins. We find that two putative transcriptional mediators (RIP140 and
      SRC-1) exhibit hormone-dependent association with wild-type TR. In comparison,
      the interaction of this natural mutant (L454V) and artificial mutants (L454A,
      E457A) with RIP140 and SRC-1 is markedly reduced. Furthermore, coexpression of
      SRC-1 is able to restore the transcriptional activity of the L454V mutant
      receptor, indicating that the interaction of this residue with accessory proteins
      is critical for transcriptional activation. Finally, the occurrence of the L454V
      mutation in resistance to thyroid hormone, together with impaired negative
      regulation of the thyroid-stimulating hormone alpha promoter by this mutant,
      suggests that the amphipathic alpha-helix also mediates hormone-dependent
      transcriptional inhibition, perhaps via interaction with these or other accessory
      factors.

PMID- 8990195
TI  - The qualitative nature of the primary immune response to HIV infection is a
      prognosticator of disease progression independent of the initial level of plasma
      viremia.
AB  - Following infection of the host with a virus, the delicate balance between virus
      replication/spread and the immune response to the virus determines the outcome of
      infection, i.e., persistence versus elimination of the virus. It is unclear,
      however, what relative roles immunologic and virologic factors play during
      primary viral infection in determining the subsequent clinical outcome. By
      studying a cohort of subjects with primary HIV infection, it has been
      demonstrated that qualitative differences in the primary immune response to HIV,
      but not quantitative differences in the initial levels of viremia are associated
      with different clinical outcomes.

PMID- 8990196
TI  - Models of DNA structure achieve almost perfect discrimination between normal
      prostate, benign prostatic hyperplasia (BPH), and adenocarcinoma and have a high
      potential for predicting BPH and prostate cancer.
AB  - In our previous studies of DNA, wavenumber-absorbance relationships of infrared
      spectra analyzed by principal components analysis (PCA) were expressed as points
      in space. Each point represented a highly discriminating measure of structural
      modifications that altered vibrational and rotational motion, thus changing the
      spatial orientation of the points. PCA/Fourier transform-infrared technology has
      now provided a virtually perfect separation of clusters of points representing
      DNA from normal prostate tissue, BPH, and adenocarcinoma. The findings suggest
      that the progression of normal prostate tissue to BPH and to prostate cancer
      involves structural alterations in DNA that are distinctly different. The
      hydroxyl radical is likely a major contributor to these structural alterations,
      which is consistent with previous studies of breast cancer. Models based on
      logistic regression of infrared spectral data were used to calculate the
      probability of a tissue being BPH or adenocarcinoma. The models had a sensitivity
      and specificity of 100% for classifying normal vs. cancer and normal vs. BPH, and
      close to 100% for BPH vs. cancer. Thus, the PCA/Fourier transform-infrared
      technology was shown to be a powerful means for discriminating between normal
      prostate tissue, BPH and prostate cancer and has considerable promise for risk
      prediction and clinical application.

PMID- 8990197
TI  - Cyclic AMP and its receptor protein negatively regulate the coordinate expression
      of cholera toxin and toxin-coregulated pilus in Vibrio cholerae.
AB  - Insertion mutations in two Vibrio cholerae genes, cya and crp, which encode
      adenylate cyclase and the cyclic AMP (cAMP) receptor protein (CRP), respectively,
      derepressed the expression of a chromosomal cholera toxin (CT) promoter-lacZ
      fusion at the nonpermissive temperature of 37 degrees C. In the classical biotype
      strain O395, the crp mutation increased the production of both CT and toxin
      coregulated pilus (TCP) in vitro under a variety of growth conditions not
      normally permissive for their expression. The most dramatic increase in CT and
      TCP was observed with the crp mutant in Luria-Bertani (LB) medium pH 8.5, at 30
      degrees C. El Tor biotype strains differ from classical strains in that they do
      not produce CT or TCP when grown in LB media. Incorporation of the crp mutation
      into El Tor strain C6706 permitted production of these proteins in LB medium pH
      6.5, at 30 degrees C. In the infant mouse cholera model, the crp mutation
      decreased colonization in both biotypes at least 100-fold relative to the wild
      type strains. The data presented here suggest a model whereby cAMP-CRP negatively
      regulates the expression of CT and TCP in both classical and El Tor biotypes
      under certain environmental conditions and also influences pathogenesis by
      regulating other processes necessary for optimal growth in vivo.

PMID- 8990198
TI  - Capsule switching of Neisseria meningitidis.
AB  - The different sialic acid (serogroups B, C, Y, and W-135) and nonsialic acid
      (serogroup A) capsular polysaccharides expressed by Neisseria meningitidis are
      major virulence factors and are used as epidemiologic markers and vaccine
      targets. However, the identification of meningococcal isolates with similar
      genetic markers but expressing different capsular polysaccharides suggests that
      meningococcal clones can switch the type of capsule they express. We identified,
      except for capsule, isogenic serogroups B [(alpha2-->8)-linked polysialic acid]
      and C [(alpha2-->9)-linked polysialic acid] meningococcal isolates from an
      outbreak of meningococcal disease in the U. S. Pacific Northwest. We used these
      isolates and prototype serogroup A, B, C, Y, and W-135 strains to define the
      capsular biosynthetic and transport operons of the major meningococcal serogroups
      and to show that switching from the B to C capsule in the outbreak strain was the
      result of allelic exchange of the polysialyltransferase. Capsule switching was
      probably the result of transformation and horizontal DNA exchange in vivo of a
      serogroup C capsule biosynthetic operon. These findings indicate that closely
      related virulent meningococcal clones may not be recognized by traditional
      serogroup-based surveillance and can escape vaccine-induced or natural protective
      immunity by capsule switching. Capsule switching may be an important virulence
      mechanism of meningococci and other encapsulated bacterial pathogens. As vaccine
      development progresses and broader immunization with capsular polysaccharide
      conjugate vaccines becomes a reality, the ability to switch capsular types may
      have important implications for the impact of these vaccines.

PMID- 8990199
TI  - Molecular phylogeny of Archaea from soil.
AB  - Cultivation methods have contributed to our present knowledge about the presence
      and diversity of microbes in naturally occurring communities. However, it is well
      established that only a small fraction of prokaryotes have been cultivated by
      standard methods and, therefore, the prokaryotes that are cultivated may not
      reflect the composition and diversity within those communities. Of the two
      prokaryotic phylogenetic domains, Bacteria and Archaea, members of the former
      have been shown to be ubiquitous in nature, with ample evidence of vast
      assemblages of uncultured organisms. There is also now increasingly compelling
      evidence that the Archaea, which were once thought to occupy a limited number of
      environments, are also globally widespread. Here we report the use of molecular
      phylogenetic techniques, which are independent of microbial cultivation, to
      conduct an assessment of Archaea in a soil microbial community. Small subunit
      ribosomal RNA genes of Archaea were amplified from soil and cloned. Phylogenetic
      and nucleotide signature analyses of these cloned small subunit ribosomal RNA
      gene sequences revealed a cluster of Archaea from a soil microbial community that
      diverge deeply from the crenarchaeotal line of descent and has the closest
      affiliation to the lineage of planktonic Archaea. The identification and
      phylogenetic classification of this archaeal lineage from soil contributes to our
      understanding of the ecological significance of Archaea as a component of
      microbial communities in non-extreme environments.

PMID- 8990200
TI  - The choroid plexus epithelium is the site of the organic anion transport protein
      in the brain.
AB  - The mRNA for organic anion transport protein (oatp) was previously shown to be
      present in abundance in liver and kidney, and in small amounts in brain. Data
      obtained from experiments with reverse transcriptase-PCR techniques and in situ
      hybridization analysis showed that the oatp mRNA is present within the brain,
      localized to the choroid plexus. A sequence-specific antibody to the oatp
      polypeptide demonstrated the presence of the expected polypeptide with a
      molecular weight of 80,000 plus an immunoreactive species with a higher molecular
      weight in preparations of choroid plexus membranes. Examination of the choroid
      plexus by fluorescence confocal microscopy revealed that immunoreactive oatp
      polypeptide is localized to the apical surface of the choroid plexus epithelial
      cells, which contacts the cerebrospinal fluid. This localization of oatp is
      consistent with previous experiments showing vectorial transport of organic
      anions between the choroid plexus and the cerebrospinal fluid.

PMID- 8990201
TI  - Distinct roles of C2A and C2B domains of synaptotagmin in the regulation of
      exocytosis in adrenal chromaffin cells.
AB  - Synaptotagmin that contains two repeats of C2 regulatory domains is considered to
      be involved in neurotransmitter release. To reveal the roles of synaptotagmin in
      the regulation of exocytosis, we examined the effects of antibodies against C2A
      and C2B domains on Ca2+-evoked catecholamine (CA) release from digitonin
      permeabilized adrenal chromaffin cells, resolving the Ca2+-evoked release into
      ATP-dependent priming and ATP-independent Ca2+-triggered steps. Anti-C2A antibody
      clearly reduced the ATP-independent release, suggesting that the C2A domain
      directly facilitate or promote Ca2+-triggered step, vesicular fusion. In
      contrast, anti-C2B antibody did not affect Ca2+-evoked release by itself, but
      significantly increased the spontaneous Ca2+-independent release. In addition,
      inositol high-polyphosphate series (IHPS) that bind the C2B domain inhibited both
      the ATP-independent Ca2+-evoked release and the spontaneous release in a dose
      dependent manner. The inhibition by IHPS was totally reversed by anti-C2B
      antibody and significantly reversed by high concentration of Ca2+. These results
      suggest that IHPS binding to C2B domain arrests membrane fusion by presumably
      preventing interaction of synaptotagmin with phospholipids or with proteins of
      plasma membrane. Thus, IHPS binding to the C2B domain might keep the docked or
      primed vesicles away from spontaneous fusion at resting level of intracellular
      Ca2+. Binding of the increased intracellular Ca2+ to the C2A domain may
      facilitate or trigger the vesicular fusion by releasing this suppression by IHPS.

PMID- 8990202
TI  - Newborn primate infants are entrained by low intensity lighting.
AB  - At the present time we do not know when the circadian timing system of human
      infants becomes responsive to light. Because of human study limitations, it is
      not currently possible to address this issue in clinical studies. Therefore, to
      provide insights into when the circadian system of humans becomes responsive to
      light, baboons were studied. We first assessed if the biological clock located in
      suprachiasmatic nuclei (SCN) is responsive to light at birth. When term newborn
      infants were exposed to bright light at night (5000 lux), SCN metabolic activity
      and c-fos mRNA expression increased, indicating the presence of photic
      responsiveness. When photic entrainment of developing rhythmicity was examined in
      infants, low intensity (200 lux) cycled lighting was sufficient to entrain
      circadian phase. However, low intensity lighting was not sufficient to induce
      changes in SCN metabolic activity or c-fos mRNA expression. Phase-response
      studies indicated that light exposure (200 lux) before the onset of activity most
      effectively shifted circadian phase. These data provide direct evidence that the
      SCN are responsive to visually mediated light information in a primate at birth.
      Further consideration of lighting conditions that infants are exposed to is
      therefore warranted.

PMID- 8990203
TI  - Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary
      degeneration: sequestration of microtubule-associated proteins 1 and 2 and the
      disassembly of microtubules by the abnormal tau.
AB  - The microtubule-associated protein (MAP) tau is abnormally hyperphosphorylated in
      Alzheimer disease and accumulates in neurons undergoing neurofibrillary
      degeneration. In the present study, the associations of the Alzheimer
      hyperphosphorylated tau (AD P-tau) with the high molecular weight MAPs (HMW-MAPs)
      MAP1 and MAP2 were investigated. The AD P-tau was found to aggregate with MAP1
      and MAP2 in solution. The association of AD P-tau to the MAPs resulted in
      inhibition of MAP-promoted microtubule assembly. However, unlike the
      coaggregation of AD P-tau and normal tau, the association between AD P-tau and
      the HMW-MAPs did not result in the formation of filaments/tangles. The affinity
      of the tau-AD P-tau association was higher than that of HMW-MAPs-AD P-tau because
      normal tau inhibited the latter binding. The association between AD P-tau and the
      HMW-MAPs also appeared to occur in situ because these proteins cosedimented from
      the Alzheimer brain extracts, and, in the sediment, the levels of the HMW-MAPs
      correlated with the levels of AD P-tau. These studies suggested that the
      abnormally phosphorylated tau can sequester both normal tau and HMW-MAPs and
      disassemble microtubules but, under physiological conditions, can form tangles of
      filaments only from tau.

PMID- 8990204
TI  - Chick pineal clock regulates serotonin N-acetyltransferase mRNA rhythm in
      culture.
AB  - Melatonin production in the chick pineal gland is high at night and low during
      the day. This rhythm reflects circadian changes in the activity of serotonin N
      acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT; EC 2.3.1.87), the
      penultimate enzyme in melatonin synthesis. In contrast to the external regulation
      of pineal rhythms in mammals by the suprachiasmatic nucleus, rhythmic changes in
      AA-NAT activity in cultured chick pineal cells are controlled by an oscillator
      located in the pineal cells themselves. Here we present evidence that the chick
      pineal clock generates a rhythm in the abundance of AA-NAT mRNA in cultured cells
      that parallels the rhythm in AA-NAT activity. In contrast, elevating cAMP by
      forskolin treatment markedly increases AA-NAT activity without producing strong
      changes in AA-NAT mRNA levels, and lowering cAMP by norepinephrine treatment
      decreases enzyme activity without markedly decreasing mRNA. These results suggest
      that clock-controlled changes in AA-NAT activity occur primarily through changes
      at the mRNA level, whereas cAMP-controlled changes occur primarily through
      changes at the protein level. Related studies indicate that the clock-dependent
      nocturnal increase in AA-NAT mRNA requires gene expression but not de novo
      protein synthesis, and that AA-NAT mRNA levels are suppressed at all times of the
      day by a rapidly turning over protein. Further analysis of the regulation of
      chick pineal AA-NAT mRNA is likely to enhance our understanding of the molecular
      basis of vertebrate circadian rhythms.

PMID- 8990205
TI  - Functional expression of a novel human neurokinin-3 receptor homolog that binds
      [3H]senktide and [125I-MePhe7]neurokinin B, and is responsive to tachykinin
      peptide agonists.
AB  - In 1992, Xie et al. identified a cDNA sequence in the expression cloning search
      for the kappa opioid receptor. When the cDNA was expressed in Cos-7 cells,
      binding of opioid compounds was observed to be of low affinity and without kappa,
      mu, or delta selectivity [Xie, G.-X., Miyajima, A. and Goldstein, A. (1992) Proc.
      Natl. Acad. Sci. USA 89, 4124-4128]. This cDNA was highly homologous to the human
      neurokinin-3 (NK-3) receptor sequence, and displayed lower homology to NK-1 and
      NK-2 sequences. This sequence was stably expressed in Chinese hamster ovary
      cells, which do not express neurokinin receptors naturally, and ligand binding
      and second messenger characteristics were compared with a human NK-3 receptor.
      The NK-3 receptor homolog bound [3H] senktide with a Kd of 39 nM, similar to that
      of the NK-3 receptor. The rank order of tachykinin peptides competing for
      [3H]senktide binding at the NK-3 receptor homolog was [MePhe7]neurokinin B >
      senktide > substance P = neurokinin A > neurokinin B. This cell line also bound
      [125I-MePhe7]neurokinin B; however, neurokinin B was an effective competitor.
      Tachykinin peptides stimulated both inositol phospholipid hydrolysis and
      arachidonic acid release at NK-3 and NK-3 receptor homolog cell lines, with
      similar rank orders of potency of [MePhe7] neurokinin B = neurokinin B = senktide
      > NKA = substance P. These results indicate that expression of the NK-3 receptor
      homolog cDNA in the Chinese hamster ovary cell system induces the expression of a
      receptor site with many similarities but certain key differences from that of the
      human NK-3 receptor. The results are discussed with reference to the existence of
      a novel human tachykinin receptor.

PMID- 8990206
TI  - Surface dynamics in living acinar cells imaged by atomic force microscopy:
      identification of plasma membrane structures involved in exocytosis.
AB  - The dynamics at the plasma membrane resulting from secretory vesicle docking and
      fusion and compensatory endocytosis has been difficult to observe in living cells
      primarily due to limited resolution at the light microscopic level. Using the
      atomic force microscope, we have been able to image and record changes in plasma
      membrane structure at ultrahigh resolution after stimulation of secretion from
      isolated pancreatic acinar cells. "Pits" measuring 500-2000 nm and containing 3
      20 depressions measuring 100-180 nm in diameter were observed only at the apical
      region of acinar cells. The time course of an increase and decrease in
      "depression" size correlated with an increase and decrease of amylase secretion
      from live acinar cells. Depression dynamics and amylase release were found to be
      regulated in part by actin. No structural changes were identified at the
      basolateral region of these cells. Our results suggest depressions to be the
      fusion pores identified earlier in mast cells by freeze-fracture electron
      microscopy and by electrophysiological measurements. The atomic force microscope
      has enabled us to observe plasma membrane dynamics of the exocytic process in
      living cells in real time.

PMID- 8990208
TI  - An Arabidopsis photolyase mutant is hypersensitive to ultraviolet-B radiation.
AB  - Photolyases are DNA repair enzymes that use energy from blue light to repair
      pyrimidine dimers. We report the isolation of an Arabidopsis thaliana mutant
      (uvr2-1) that is defective in photorepair of cyclobutylpyrimidine dimers (CPDs).
      Whereas uvr2-1 is indistinguishable from wild type in the absence of UV light,
      low UV-B levels inhibit growth and cause leaf necrosis. uvr2-1 is more sensitive
      to UV-B than wild type when placed under white light after UV-B treatment. In
      contrast, recovery in darkness or in light lacking photoreactivating blue light
      results in equal injury in uvr2-1 and wild type. The uvr2-1 mutant is unable to
      remove CPDs in vivo, and plant extracts lack detectable photolyase activity. This
      recessive mutation segregates as a single gene located near the top of chromosome
      1, and is a structural gene mutation in the type II CPD photolyase PHR1. This
      mutant provides evidence that CPD photolyase is required for plant survival in
      the presence of UV-B light.

PMID- 8990207
TI  - In vitro motility of AtKCBP, a calmodulin-binding kinesin protein of Arabidopsis.
AB  - AtKCBP is a calcium-dependent calmodulin-binding protein from Arabidopsis that
      contains a conserved kinesin microtubule motor domain. Calmodulin has been shown
      previously to bind to heavy chains of the unconventional myosins, where it is
      required for in vitro motility of brush border myosin I, but AtKCBP is the first
      kinesin-related heavy chain reported to be capable of binding specifically to
      calmodulin. Other kinesin proteins have been identified in Arabidopsis, but none
      of these binds to calmodulin, and none has been demonstrated to be a microtubule
      motor. We have tested bacterially expressed AtKCBP for the ability to bind
      microtubules to a glass surface and induce gliding of microtubules across the
      glass surface. We find that AtKCBP is a microtubule motor protein that moves on
      microtubules toward the minus ends, with the opposite polarity as kinesin. In the
      presence of calcium and calmodulin, AtKCBP no longer binds microtubules to the
      coverslip surface. This contrasts strikingly with the requirement of calmodulin
      for in vitro motility of brush border myosin I. Calmodulin could regulate AtKCBP
      binding to microtubules in the cell by inhibiting the binding of the motor to
      microtubules. The ability to bind to calmodulin provides an evolutionary link
      between the kinesin and myosin motor proteins, but our results indicate that the
      mechanisms of interaction and regulation of kinesin and myosin heavy chains by
      calmodulin are likely to differ significantly.

PMID- 8990209
TI  - Cloning of the gene for monogalactosyldiacylglycerol synthase and its
      evolutionary origin.
AB  - Monogalactosyldiacylglycerol (MGDG) synthase (UDPgalactose:1,2-diacylglycerol 3
      beta-D-galactosyltransferase; EC 2.4.1.46) catalyzes formation of MGDG, a major
      structural lipid of chloroplast. We cloned a cDNA for the synthase from cucumber
      cDNA library. The full-length cDNA clone was 2142 bp, and it contains a 1575-bp
      open reading frame encoding 525 aa. The open reading frame consists of the
      regions for a mature protein (422 aa; Mr of 46,552) and transit peptide to
      chloroplast (103 aa). Although the molecular weight of mature protein region
      matched that purified from cucumber cotyledons, it was quite different from those
      purified from spinach (approximately 20 kDa) reported by other groups. The mature
      region of the protein was expressed in Escherichia coli as a fusion protein with
      glutathione S-transferase. The expression in E. coli showed that the protein
      catalyzed MGDG synthesis very efficiently. Therefore, we concluded that the cDNA
      encodes MGDG synthase in cucumber. In addition, the deduced amino acid sequence
      of the MGDG synthase cDNA showed homology with MurG of Bacillus subtilis and E.
      coli, which encode a glycosyltransferase catalyzing the last step of
      peptidoglycan synthesis in bacteria. This sequence homology implies that the
      machinery of chloroplast membrane biosynthesis is evolutionarily derived from
      that of cell wall biosynthesis in bacteria. This is consistent with the
      endosymbiotic hypothesis of chloroplast formation.

PMID- 8990210
TI  - Heterogeneities in the transmission of infectious agents: implications for the
      design of control programs.
AB  - From an analysis of the distributions of measures of transmission rates among
      hosts, we identify an empirical relationship suggesting that, typically, 20% of
      the host population contributes at least 80% of the net transmission potential,
      as measured by the basic reproduction number, R0. This is an example of a
      statistical pattern known as the 20/80 rule. The rule applies to a variety of
      disease systems, including vector-borne parasites and sexually transmitted
      pathogens. The rule implies that control programs targeted at the "core" 20%
      group are potentially highly effective and, conversely, that programs that fail
      to reach all of this group will be much less effective than expected in reducing
      levels of infection in the population as a whole.

PMID- 8990211
TI  - Place cells and place navigation.
AB  - The assumption that hippocampal place cells (PCs) form the neural substrate of
      cognitive maps can be experimentally tested by comparing the effect of
      experimental interventions on PC activity and place navigation. Conditions that
      interfere with place navigation (darkness, cholinergic blockade) but leave PC
      activity unaffected obviously disrupt spatial memory at a post-PC level.
      Situations creating a conflict between egocentric and allocentric orientation
      (place navigation in the Morris water maze filled with slowly rotating water)
      slow down spatial learning. PC recording in rats searching food pellets in a
      rotating arena makes it possible to determine which firing fields are stable
      relative to the room (allocentrically dependent on sighted extramaze landmarks),
      to the surface of the arena (dependent on egocentric path integration mechanisms
      and intra-arena cues), or disappear during rotation. Such comparison is made
      possible by the computerized tracking system simultaneously displaying a rat's
      locomotion and the respective firing rate maps both in the room reference and
      arena reference frames. More severe conflict between allocentric and egocentric
      inputs is produced in the field clamp situation when the rat searching food in a
      ring-shaped arena is always returned by rotation of the arena to the same
      allocentric position. Ten-minute exposure to this condition caused subsequent
      disintegration or remapping of 70% PCs (n = 100). Simultaneous examination of PC
      activity and navigation is possible in the place avoidance task. A rat searching
      food in a stationary or rotating arena learns to avoid an allocentrically or
      egocentrically defined location where it receives mild electric footshock. In the
      place preference task the rat releases pellet delivery by entering an unmarked
      goal area and staying in it for a criterion time. Both tasks allow direct
      comparison of the spatial reference frames used by the PCs and by the behaving
      animal.

PMID- 8990212
TI  - BRCA1 mutation testing: controversies and challenges.

PMID- 8990213
TI  - Clinical implications of a sandwich enzyme immunoassay for big endothelin-1.

PMID- 8990214
TI  - Methodology and subspecialty consolidation in the clinical laboratory.

PMID- 8990215
TI  - Association between genetic variations of apo AI-CIII-AIV cluster gene and
      hypertriglyceridemic subjects.
AB  - Several studies have suggested that genetic variations of the apolipoprotein
      (apo) AI-CIII-AIV cluster gene are associated with hyperlipidemia or
      atherosclerosis. These investigations were carried out mainly with Caucasian
      groups; there have been few associated studies involving non-Caucasian groups.
      This study was conducted to elucidate the association between five restriction
      fragment length polymorphisms (RFLPs) of the apo AI-CIII-AIV cluster gene and
      Korean hypertriglyceridemic subjects. The rare allele frequencies of the XmnI and
      SstI polymorphic sites in the patients were significantly higher than those of
      the control group (P <0.05). These two polymorphic sites had relation to linkage
      disequilibrium in the hypertriglyceridemic subjects (delta = -0.2733). In
      addition, S2 allele frequency of the SstI RFLP in Koreans was more frequent than
      that of Caucasians reported previously. The rare allele of XmnI and SstI
      polymorphic sites was associated with increased triglyceride concentrations in
      the hypertriglyceridemic group (P <0.005). Koreans have a much lower prevalence
      of hyperlipidemia than Caucasians. Nevertheless, this study showed a similar
      trend with results from Caucasian groups, thereby confirming that genetic
      variations of the apo AI-CIII-AIV cluster gene are likely to be significant
      markers for hypertriglyceridemic subjects. Thus, RFLP loci of the apo AI-CIII-AIV
      cluster gene may be a useful genetic marker for clinical or population studies.

PMID- 8990216
TI  - Development of reverse dot-blot system for screening of mitochondrial DNA
      mutations associated with Leber hereditary optic atrophy.
AB  - We developed a diagnostic test based on the reverse dot-blot principle, in which
      five mitochondrial point mutations responsible for Leber hereditary optic
      neuropathy (LHON) were screened simultaneously. A series of wild-type and mutant
      oligonucleotides representing each mutation were covalently bound to a single
      nylon membrane strip. The target sites were amplified in a multiplex PCR and the
      products were hybridized to the membrane. Detection is based on
      chemiluminescence. To test the developed assay, 47 patients suspected of having
      LHON were screened. In 11 cases (23%) the diagnosis of LHON could be confirmed
      (3460, 1; 9804, 1; 11778, 5; 14484, 3; 15257, 1). The results suggest that the
      clinical identification of the mitochondrial defect is not trivial and the
      availability of a rapid screening method simplifies the molecular analysis of
      these cases.

PMID- 8990218
TI  - Optimization of single-strand conformation polymorphism analysis in the presence
      of polyethylene glycol.
AB  - We report optimization of single-strand conformation polymorphism (SSCP) analysis
      in the presence of polyethylene glycol. The protocol developed separates single
      strand conformers in a much shorter time (1-3 h) than conventional SSCP protocols
      and broadens the applicability of SSCP analysis from 150 to as much as 500 bp of
      DNA by different percentages of GC content present. We conclude that addition of
      polyethylene glycol helps improve the differential separation of conformers and,
      in combination with high-resolution polyacrylamide gel electrophoresis, offers an
      alternative to previous SSCP analysis protocols. This protocol should be very
      useful for clinical applications in routine detection of mutations as well as for
      research purposes.

PMID- 8990217
TI  - Direct detection of mutations in the breast and ovarian cancer susceptibility
      gene BRCA1 by PCR-mediated site-directed mutagenesis.
AB  - The tumor suppressor genes BRCA1 and BRCA2, which confer increased susceptibility
      to breast and (or) ovarian cancer, were recently identified. Mutation analysis of
      BRCA1 has demonstrated significant allelic heterogeneity; however, some distinct
      mutations have been detected in unrelated individuals. The most notable is the
      185delAG mutation, which occurs at an estimated frequency of approximately 1% in
      individuals of Ashkenazi Jewish descent [1]. Although consensus has not been
      reached regarding clinical testing for mutations in BRCA1, a tiered strategy may
      be appropriate, in which direct testing for the more common mutations is one
      component. Specific alleles can be detected by using PCR-mediated site-directed
      mutagenesis (PSM), which alters the PCR products derived from either the wild
      type or mutant allele to create or destroy a restriction endonuclease recognition
      site. Recognition sites are introduced by a base substitution in one of the
      primers. The alleles are then resolved by electrophoresis of the digested PCR
      products. We have applied this technique to the detection of four BRCA1
      mutations: 185delAG, 5382insC, E1250X, and R1443X. Another mutation, 1294de140,
      can be resolved from the wild-type allele by high-resolution gel electrophoresis
      alone. The PSM technique is sensitive, does not require radioactivity, and is
      specific for individual mutations.

PMID- 8990219
TI  - Cation-exchange HPLC evaluated for presumptive identification of hemoglobin
      variants.
AB  - A battery of relatively simple tests allows the presumptive identification of
      hemoglobin (Hb) variants, making unnecessary structural analysis by protein
      chemistry methods or DNA sequencing. The primary step in this strategy involves
      the use of a matrix of electrophoretic mobilities obtained under various
      experimental conditions. This leads to an unambiguous result in approximately 90%
      of the cases. Additional tests are required to characterize with more confidence
      the remaining 10%. We describe here the use of cation-exchange HPLC on the Bio
      Rad Variant automated analyzer with the "beta Thalassemia Short" program. By
      comparing the elution time of 125 human Hb mutants, we found that some variants
      with almost identical pI values or produced by the same type of amino acid
      substitution displayed different elution times. We present several examples in
      which use of the HPLC profile helped establish the diagnosis.

PMID- 8990220
TI  - Ligase chain reaction assay for human mutations: the Sickle Cell by LCR assay.
AB  - We can detect the beta-globin gene sickle cell mutation by using an assay based
      on the ligase chain reaction. The simultaneous amplification of the human growth
      hormone gene in the same reaction serves as a control for the amount of template
      DNA or amplification efficiency. Ligation products, which are biotinylated at one
      end and tagged with an arbitrary "tail" sequence at the other, are captured by
      hybridization to "tail"-complementary oligonucleotides immobilized on polystyrene
      microwells. The captured ligation products are detected colorimetrically by use
      of streptavidin-alkaline phosphatase conjugate. In a study of 24 subjects, the
      assay unequivocally discriminated among normal, carrier, and sickle cell
      genotypes.

PMID- 8990221
TI  - Determination of xylosyltransferase activity in serum with recombinant human
      bikunin as acceptor.
AB  - Xylosyltransferase (XT) is the chain-initiating enzyme of the biosynthesis of
      chondroitin sulfate. So far, XT activity has been detected by incorporation of
      [14C]xylose in chemically deglycosylated cartilage proteoglycan or silk fibroin.
      However, these acceptors allow no reliable determination in blood. We found that
      recombinant bikunin is an excellent acceptor for XT. The Michaelis-Menten
      constants for the xylosylation of silk, deglycosylated cartilage proteoglycans,
      and bikunin were 545, 155, and 0.9 micromol/L, respectively. With recombinant
      bikunin as acceptor, we developed a sensitive assay that allows a precise
      determination of XT activity in serum. We measured the serum XT activities of 500
      blood donors and observed a considerable sex and age dependence. XT activities in
      men (0.77-1.50 mU/L) were approximately 30% higher than in women (0.58-1.20 mU/L)
      and reached a maximum in donors of approximately 40 years of age. During the
      menstrual cycle, serum XT activity showed a significant coincidence with the beta
      estradiol concentration, and in the first trimester of pregnancy we observed a
      strong increase in serum XT activity.

PMID- 8990222
TI  - Variability in the measurement of C-reactive protein in healthy subjects:
      implications for reference intervals and epidemiological applications.
AB  - We developed a reproducible ELISA for C-reactive protein (CRP), calibrated with
      WHO Reference Material, for which intra- and interassay CVs were 3.0% and 6.0%,
      respectively. Analytical recovery was 97.9%. The distribution of CRP in a healthy
      blood donor population (n = 143) was nongaussian, with 2.5th, 50th, and 97.5th
      percentile values of 0.08, 0.64, and 3.11 mg/L, respectively. There was no sex
      related difference, and the association with age was weak. In a study of
      variability [by the method of Fraser and Harris (Crit Rev Clin Lab Sci
      1989;27:409-37)], the analytical variability was 5.2%; the within-subject
      variability, CVI, was 42.2%; and the between-subject variability, CVG, was 92.5%.
      The critical difference for sequential values significant at P < or =0.05 (i.e.,
      the smallest percentage change unlikely to be due to analytical variability or
      CVI) was calculated as 118%, and the index of individuality, CVI/CVG, was 0.46.
      This suggests that CRP, like many clinical chemistry analytes, has limited
      usefulness in detecting early disease-associated changes when used in conjunction
      with a healthy reference interval. From a molecular epidemiological standpoint,
      the usefulness of CRP in longitudinal studies is suggested by the small index of
      individuality and by observations that (a) short-term fluctuations were
      infrequent, (b) all data stayed within the reference interval, and (c) relative
      rankings of the subjects over 6 months only moderately deteriorated.

PMID- 8990223
TI  - Development of ELISA to estimate thymosin alpha1, the N terminus of prothymosin
      alpha, in human tumors.
AB  - We reported that tumor content of prothymosin alpha (ProT alpha) is a
      proliferation index of human breast tumors that might be used to identify
      patients at high risk for distant metastasis (Dominguez et al., Eur J Cancer
      1993; 29A:893-7). In that study ProT alpha concentrations were measured by a RIA;
      here we present an alternative nonisotopic assay that could be used in a standard
      clinical laboratory. Main features of the ELISA are: (a) A recombinant fusion
      protein glutathione S-transferase (GST)-human ProT alpha was used to coat the
      microtiter plates; (b) we used a polyclonal antiserum raised in rabbits that
      detects thymosin alpha1, the NH2-terminal fragment of ProT alpha; (c) it is as
      sensitive as the RIA; (d) it is faster than the RIA. ProT alpha concentrations in
      various human tumors (skin, esophagus, colorectal, and breast) as assessed by
      ELISA were comparable with, although twofold greater than, the values previously
      estimated by RIA.

PMID- 8990224
TI  - Sandwich-type enzyme immunoassay for big endothelin-I in plasma: concentrations
      in healthy human subjects unaffected by sex or posture.
AB  - A sandwich-type enzyme immunoassay has been developed for measuring human big
      endothelin-1 (big ET-1) in human plasma and supernatant fluids from human cell
      cultures. Big ET-1 is the precursor of endothelin 1 (ET-1), the most potent
      vasoconstrictor known. A rabbit antibody raised against the big ET-1 COOH
      terminus fragment was used as an immobilized antibody (anti-P16). The Fab'
      fragment of a monoclonal antibody (1B3) raised against the ET-1 loop fragment was
      used as the enzyme-labeled antibody, after being coupled to acetylcholinesterase.
      The lowest detectable value in the assay was 1.2 pg/mL (0.12 pg/well). The assay
      was highly specific for big ET-1, demonstrating no cross-reactivity with ET-1,
      <0.4% cross-reactivity with big endothelin-2 (big ET-2), and <0.1% with big
      endothelin-3 (big ET-3). We used this assay to evaluate the effect of two
      different postural positions (supine and standing) on plasma big ET-1
      concentrations in 11 male and 11 female healthy subjects. Data analysis revealed
      that neither sex nor body position influenced plasma big ET-1 concentrations.
      This assay should thus permit the detection of possible variations in plasma
      concentrations of big ET-1 in certain pathologies and, in association with ET-1
      assay, make possible in vitro study of endothelin-converting enzyme activity in
      cell models. Such studies could clarify the physiological and clinical roles of
      this family of peptides.

PMID- 8990225
TI  - Two-site immunofluorometric assay of intact salmon calcitonin with improved
      sensitivity.
AB  - We recently developed a two-site immunofluorometric assay (IFMA) of salmon
      calcitonin (SCT) by DELFIA (dissociation enhancement lanthanide
      fluoroimmunoassay) technique using the same polyclonal antibodies both for
      "catching" the antigen and for signaling. In the present study we used a
      monoclonal antibody to SCT 1-11 as the capture antibody. This antibody was
      biotinylated before use in streptavidin-coated microtitration plates. The
      polyclonal antibody labeled with Eu chelate was used as a signaling marker. This
      combination of antibodies resulted in an assay that was three to four times more
      sensitive than the previous IFMA, with a detection limit of 0.3 pmol/L serum.
      Intact SCT 1-32 was detected by the assay (recoveries 94-96%), but not the
      fragments SCT 1-11 and SCT 10-32 or human calcitonin. Dilutions of plasma samples
      containing SCT were parallel to the calibration curve of SCT 1-32.
      Pharmacokinetic studies of SCT, 100 IU administered intramuscularly to 10 men,
      indicated peak serum concentrations of 32-128 pmol/L within 10-20 min with
      apparent half-life of 56+/-18 min (mean+/-SD). This new assay will allow study of
      the pharmacokinetics of new calcitonin preparations that do not require
      injection.

PMID- 8990226
TI  - Adaptation of latex-enhanced assay for percent glycohemoglobin to a Dade
      Dimension analyzer.
AB  - At present no method for glycohemoglobin (%HbA1c) is automated on a main-line
      analyzer to allow joint measurement with other indicators of diabetic control
      such as glucose and cholesterol. We describe an adaptation of a latex-enhanced
      competitive immunoassay for quantifying %HbA1c to the Dade International
      Dimension analyzer. After a manual hemolysis step, HbA1c and total hemoglobin
      (Hb) are determined separately. The concentration of glycated beta-subunit is
      obtained from the immunoassay, whereas Hb is assessed colorimetrically from a
      derivatized form. Both reactions were fully optimized for accuracy, precision,
      and specificity on the Dimension; stabilities of reagents and calibration were
      established; and potential interferences were assessed. The analyzer gave
      reliable results over the required clinical range of 1-15% HbA1c. Within-run and
      total assay variation were within 5% of the target CV limits, as determined by
      ANOVA with three representative sample pools across 20 days. Close agreement with
      an established HPLC procedure and a commercially available enzyme immunoassay was
      observed for 140 samples from clinically defined patient groups. Additional
      samples from patients with hemoglobinopathies (n = 20) demonstrated a more
      complex relationship between methods. We conclude that adaptation of the method
      for use with the Dimension analyzer is a valid method for quantifying %HbA1c.

PMID- 8990227
TI  - Bone sialoprotein in serum of patients with malignant bone diseases.
AB  - Bone sialoprotein (BS), a protein synthesized by osteoblasts and osteoclasts and
      highly modified posttranslationally, constitutes a predominant fraction of the
      noncollagenous organic matrix in human bone. We report an assessment of serum
      concentrations of BS in patients with malignant bone diseases. In patients with
      bone metastases (according to scintigraphic criteria), serum BS concentrations
      were greater than in patients without bone metastases (P <0.05). However, ROC
      curve analysis revealed that serum BS was inferior to serum bone alkaline
      phosphatase in discriminating between patients with and without bone metastases.
      Patients with bone metastases showed a weak correlation between serum BS
      concentrations and bone formation markers. Only "traditional" markers of bone
      formation-but not BS-were correlated with urinary deoxypyridinoline (P <0.01).
      Liver and kidney dysfunction had no significant influence on BS values in these
      patients (as assessed by analysis of variance; P >0.05). In multiple myeloma
      patients treated with corticosteroids and bisphosphonates, BS concentrations were
      lower than in tumor patients without bone metastases (P <0.001), and the
      correlation between BS concentrations and the number of bisphosphonate courses
      applied was significant (r = -0.578; P <0.05). In postmenopausal women, serum BS
      concentrations averaged 142% greater than in premenopausal women. Further studies
      should be done, therefore, to elucidate whether serum BS is able to predict high
      bone turnover after menopause.

PMID- 8990228
TI  - Comparability of a new turbidimetric digoxin test with other immunochemical tests
      and with HPLC--a multicenter evaluation.
AB  - A new turbidimetric inhibition immunoassay for digoxin (Tina-quant [a] Digoxin,
      Boehringer Mannheim) was evaluated in seven laboratories. It can be performed
      without sample pretreatment with ready-to-use reagents on nondedicated analyzers
      in combination with routine clinical chemistry. The studies revealed a good
      analytical performance: lower limit of detection 0.12 microg/L (3 SD from mean of
      blank); linearity up to 7.5 microg/L; median between-run CVs 8.1% (0.6 microg/L),
      2.8% (1.5 microg/L), 1.9% (3 microg/L); mean analytical recovery in control sera
      98-102%; slopes from 0.97 to 1.09 and intercepts from -0.28 to 0.10 microg/L in
      comparison with four immunoassays; and a high resistance to common interferents.
      The test was more resistant to digoxin-like immunoreactive factor (DLIF)
      interference than other methods, showing cross-reactivity only in some intensive
      care patient samples. Among 192 patients in whom DLIF is expected (e.g., pregnant
      women, patients with renal failure, newborns), 90% of results were < or =0.26
      microg/L digoxin. Cortisol showed no cross-reactivity and digoxigenin had a low
      reactivity. An interlaboratory survey revealed a good comparability of the Tina
      quant [a] test with the median of all methods (slope 0.99, intercept -0.06
      microg/L). An HPLC method for digoxin based on isocratic separation of samples on
      an RP-18 column followed by detection by an immunoassay yielded a reasonable
      comparability with the immunochemical tests with noncritical samples. Divergent
      results of immunoassays caused by DLIFs or different cross-reactivities with
      digoxin metabolites or derivatives can be explained by the use of this HPLC
      method.

PMID- 8990229
TI  - Lowering cutoffs for initial and confirmation testing for cocaine and marijuana:
      large-scale study of effects on the rates of drug-positive results.
AB  - A large-scale study was conducted to determine whether lowering the initial
      testing and confirmation testing cutoffs in urine would significantly affect the
      positive rates for cocaine (COC) and marijuana (THC). Customary cutoffs for COC
      are 300 microg/L and 150 microg/L for initial testing (screening) and gas
      chromatography-mass spectrometry (GC-MS; confirmation), respectively; for THC,
      the usual respective cutoffs are 50 microg/L and 10 microg/L. By applying a
      screening cutoff of 100 microg/L for COC and lowering the GC-MS cutoff to 50
      microg/L, the COC-positive rate increased from 1.2% to 2.1%. For THC, lowering
      the screening cutoff to 20 microg/L while leaving the GC-MS cutoff at 10 microg/L
      increased the THC-positive rate from 2.8% to 4.1%. These increases appear
      noteworthy.

PMID- 8990230
TI  - Effect of assay methodology on pharmacokinetic differences between cyclosporine
      Neoral and Sandimmune formulations.
AB  - The new oral formulation of cyclosporine (CsA), Neoral (CsA-N), results in
      increased area under the curve (AUC) and decreased intra- and interindividual
      variation in blood concentrations and other pharmacokinetic (PK) parameters when
      compared with the current Sand-immune (CsA-S) formulation. The present study
      examines the effect of assay methodology on variability in blood concentrations
      and PK parameters for renal transplant patients receiving CsA-N and CsA-S and
      whether this variation is reduced with CsA-N. The results show that
      interindividual variations in PK parameters for patients receiving CsA-N were
      less than those for patients receiving CsA-S. Both blood concentrations and dose
      of CsA better correlated with abbreviated (4-h) AUC after administration of CsA
      N. For both CsA-S and CsA-N, blood concentrations at 4 h postdose exhibited the
      best correlation with AUC. All samples were analyzed by three common procedures:
      HPLC, RIA, and fluorescence polarization immunoassay (FPIA). There were no
      significant differences observed in blood concentrations or PK parameters
      obtained from FPIA and RIA. HPLC results, however, were lower because of
      specificity of this method for the parent drug. The assay methodology did not
      have an effect on interindividual variability, indicating that the cross
      reactivity of metabolites in commonly used immunoassays for CsA does not
      contribute to the PK variability observed in renal transplant patients.

PMID- 8990231
TI  - Development and validation of a particle-enhanced turbidimetric inhibition assay
      for urine albumin on the Dade aca analyzer.
AB  - The measurement of urine albumin now has a well-established role in the
      monitoring of patients with diabetes mellitus. We have developed a particle
      enhanced immunoturbidimetric inhibition assay for urine albumin on the Dade aca
      analyzer. The inhibition approach removes any of the potential antigen excess
      difficulties that could be expected from the wide clinical range of urine
      albumin, but retains the sensitivity advantages of latex-enhanced
      immunoturbidimetry. Human serum albumin (HSA) is covalently attached to 40-nm
      poly(chloromethyl)styrene-modified latex particles. This reagent, along with
      monoclonal antibody to HSA, is aliquoted into the aca reagent pack along with
      polyethylene glycol 8000 in a tablet form (giving a final reaction concentration
      of 15 g/L). A 150 mmol/L phosphate buffer, pH 7.8, is used to fill the reagent
      pack in the instrument and the agglutination reaction is monitored at 340 nm. The
      sample volume is 100 microL and the calibration curve covers the range 2-250
      mg/L. Evaluation of commercial scale reagents against the Beckman Array
      nephelometric immunoassay system gave a Deming regression correlation of aca =
      0.87 x Beckman + 8.5, r = 0.995, n = 145. Mean analytical recovery was 104+/
      4.5%, n = 20, and there was no evidence of a lack of parallelism. Interassay
      precision was 8.8% at 10.0 mg/L and <2.5% at >65 mg/L. Calibrator stability was
      in excess of 60 days. A small reference range study (24-h urine collections, n =
      27) gave a mean of 5.6 mg/L with a range of 0.5-16.2 mg/L. Analytical sensitivity
      (2.5 SD from zero) was 0.40 mg/L.

PMID- 8990232
TI  - Evaluation of urinary metanephrine and normetanephrine enzyme immunoassay (ELISA)
      kits by comparison with isotope dilution mass spectrometry.
AB  - Determination of urinary 3-O-methylated catecholamines (metanephrines) is
      generally considered a principal test for the clinical chemical diagnosis of
      pheochromocytoma and is currently performed predominantly with chromatographic
      techniques such as gas-liquid chromatography and HPLC. Enzyme immunoassays based
      on microtiter plate technology have recently been developed for the quantitative
      determination of urinary metanephrine (M) and normetanephrine (NM). We compared
      the results for urinary M and NM determined by these ELISA methods with those
      obtained by a recently developed isotope dilution mass spectrometric method. From
      this comparative study we can conclude that the investigated ELISA methods are
      applicable in the quantification of urinary M and thus can be successfully used
      to establish the diagnosis of pheochromocytoma. These relatively simple methods
      can be executed in any clinical laboratory and in time may replace the present,
      more complicated, chromatographic techniques.

PMID- 8990233
TI  - Measurement of strontium in serum, urine, bone, and soft tissues by Zeeman atomic
      absorption spectrometry.
AB  - To study the possible accumulation of Sr in chronic renal failure patients,
      methods were developed for the determination of the element in serum, urine,
      bone, and soft tissues by using Zeeman atomic absorption spectrometry. Serum
      samples were diluted 1:4 with a Triton X-100-HNO3 mixture, whereas urine samples
      were diluted 1:20 with HNO3. Bone samples were digested with concentrated HNO3 in
      stoppered polytetrafluoroethylene (Teflon) tubes, whereas soft tissues were
      dissolved in a tetramethylammonium hydroxide solution in water. For serum and
      urine we used matrix-matched calibration curves, whereas bone and tissue samples
      were measured against aqueous calibrators. Atomization was performed from the
      wall of pyrolytically coated graphite tubes for all of the matrices under study.
      Both inter- and intraassay CVs were <6% (n = 12, n = 10, respectively), and the
      recovery of added analyte was close to 100% for all of the biological matrices
      under study. Detection limits were 1.2 microg/L (serum), 0.3 microg/L (urine),
      0.4 microg/g (bone), and 2.2 ng/g (soft tissues), whereas the sensitivity
      determined by the slope of the calibration curve, i.e., the amount of Sr
      producing a 0.0044 integrated absorbance change in signal, was 2.4 pg, 2.4 pg,
      3.9 pg, and 2.6 pg for these matrices respectively. We conclude that the present
      methods are precise and accurate and easily applicable for both routine use and
      research investigations. They will allow us to study the metabolism of the
      element in chronic renal failure patients and shed some light on the association
      that was recently noted between increased bone Sr concentrations and the
      development of osteomalacia in these individuals.

PMID- 8990234
TI  - Pitfalls in measuring plasma cholesterol in the Smith-Lemli-Opitz syndrome.
AB  - Correct quantitative results for plasma cholesterol, 7-dehydrocholesterol (7
      DHC), and 8-dehydrocholesterol (8-DHC) are invaluable for making the correct
      diagnosis in patients with the Smith-Lemli-Opitz syndrome (SLO) and for
      biochemical monitoring of these patients during therapy. The enzymatic method for
      cholesterol measurement based on cholesterol oxidase gives falsely high values
      for plasma cholesterol in samples from patients with SLO. Both 7-DHC and 8-DHC
      contribute substantially to the test result, given that they are accepted
      substrates of cholesterol oxidase. All cholesterol methods making use of this
      enzyme are expected to give unreliable results with plasma samples from SLO
      patients. Cholesterol values found with these methods may be low-normal in
      individual cases with SLO. Therefore, other techniques for measuring cholesterol,
      7-DHC, and 8-DHC, e.g., gas chromatography, should be used for diagnosing these
      patients and for follow-up during therapy. However, a normal value for plasma
      cholesterol, as obtained by gas chromatography, does not exclude SLO. The
      diagnosis should always be confirmed or excluded by testing for the presence of
      high concentrations of 7-DHC and 8-DHC in plasma. We found that one patient with
      a severe form of the disease had a plasma cholesterol concentration of 20
      micromol/L-to our knowledge, the lowest value ever recorded in a human being.

PMID- 8990235
TI  - REPCAT: desktop expert system for interpreting and validating laboratory data for
      pheochromocytoma diagnosis with the database application Omnis 7.
AB  - To aid in the validation and interpretive reporting of results from multianalyte
      diagnostic testing for pheochromocytoma (PHEO), we have developed a desktop
      personal computer-based laboratory expert system (REPCAT). REPCAT utilizes a
      commercial database application to run procedures that assess analytical and
      clinical data relating to patient urine or plasma samples. REPCAT was used to
      evaluate the raw data from >4000 24-h urine samples submitted to our laboratory
      for testing for the presence of PHEO. REPCAT performed equivalently to an expert
      pathologist in assessing the presence and class of PHEO (epinephrine,
      norepinephrine, or mixed secretor). No false negatives were generated and it
      assigned a correct interpretation (on the basis of subsequent clinical and
      biochemical investigation) for each of the primary diagnostic samples from these
      patients.

PMID- 8990236
TI  - Short-term and long-term variability of plasma homocysteine measurement.
AB  - Within-person and methodological variability of a given analyte are important
      elements in determining whether an individual has altered concentrations of that
      analyte. We report the short-term (1 month) within-person, between-person, and
      methodological variability of plasma homocysteine in 20 healthy participants from
      whom samples were drawn weekly for 4 weeks. The short-term between-person
      variance was high, whereas within-person and methodological variances were
      relatively very low, giving a high reliability coefficient (R) for homocysteine
      (R = 0.94). The long-term (30 months) reliability coefficient was 0.65, but was
      greatly influenced by an outlier (R = 0.82 with the outlier excluded). The data
      suggest that an individual's plasma homocysteine concentration is relatively
      constant over at least 1 month, and a single measurement characterizes the
      average concentration reasonably well.

PMID- 8990237
TI  - Reference values for plasma concentrations of vitamin E and A and carotenoids in
      a Swiss population from infancy to adulthood, adjusted for seasonal influences.
AB  - In a cross-sectional survey, plasma concentrations of alpha- and gamma
      tocopherol, alpha- and beta-carotene (cis and trans isomers), lycopene, and
      retinol were determined by reversed-phase HPLC, and ratios of plasma alpha
      tocopherol to cholesterol were calculated in 208 Swiss individuals ages 0.4-38.7
      years. The influence of age, sex, and season of sampling was studied. Age was a
      significant predictor of all plasma concentrations except alpha-carotene. No sex
      related differences were observed. Season of sampling affected alpha-tocopherol
      and retinol (higher in winter) and gamma-tocopherol and cholesterol
      concentrations (higher in winter and spring than in the other seasons). After
      correction for seasonal influences, age differences were 0.24 micromol/L per year
      for alpha-tocopherol, 0.04 micromol/L per year for retinol, and 0.04 micromol/L
      per year for cholesterol concentrations; ratios of plasma alpha-tocopherol to
      cholesterol were not affected by age. We constructed age-specific reference
      intervals from the regression line and a multiple of the standard deviation.
      Separate regression equations are presented for seasons with low and high values.

PMID- 8990238
TI  - Ascorbic acid determination with an automated enzymatic procedure.
AB  - Given the widespread interest in antioxidant nutrients, we have developed a new
      procedure that will permit the automated determination of plasma ascorbic acid
      (AA) concentration with a Roche Fara centrifugal analyzer. After the
      deproteinization of plasma with metaphosphoric acid, AA is oxidized to
      dehydroascorbic acid by AA oxidase. The product is coupled to o-phenylenediamine
      to produce a chromophore for which the absorbance is measured at 340 nm. The
      procedure allows much faster throughput than conventional HPLC methods while
      yielding results that correlate well and provide improved precision. Linearity
      extends beyond the reference range of 26.1-84.6 micromol/L, and severe hemolysis
      is the only interference identified.

PMID- 8990239
TI  - Measurement of lactate in cerebrospinal fluid in investigation of inherited
      metabolic disease.
AB  - Measurement of lactate concentrations in cerebrospinal fluid (CSF) has been
      suggested as part of the investigation of inborn errors of the electron transport
      chain, but little information exists regarding the reference range in children or
      the relationship between CSF and plasma concentrations. In 39 children without
      bacterial meningitis, diabetes, or recent seizures, we determined that the median
      (range) lactate concentrations in CSF and plasma collected concurrently were 1.4
      (0.8-2.2) and 1.5 (0.6-2.3) mmol/L; the regression equation was CSF lactate =
      (0.38+/-0.06) plasma lactate + 0.83 (r2 = 0.14). In 8 of 11 (73%) children with
      electron transport chain defects, CSF lactate was > or =3.0 mmol/L; however, 2 of
      these 8 had a normal plasma lactate concentration. CSF lactate was also increased
      in 2 children with nonketotic hyperglycinemia. The finding that CSF lactate
      concentrations may be increased despite a normal plasma lactate value in children
      with electron transport chain defects is an important clue to the diagnosis of
      these disorders.

PMID- 8990240
TI  - A case of sulfhemoglobinemia and emergency measurement of sulfhemoglobin with an
      OSM3 CO-oximeter.
AB  - We describe a case of sulfhemoglobinemia associated with toxic paint ingestion.
      Blood gases, oxygen content, and fractional hemoglobin derivatives were assayed
      with Radiometer 520 and OSM3 instruments. Although the CO-oximeters indicated the
      presence of sulfhemoglobin (SulfHb), the results were not quantitative. An OSM3
      service software program was activated to obtain the actual concentrations of the
      hemoglobin fractions. Subsequently, we evaluated the performance of the OSM3
      service program for the analysis of SulfHb by performing precision studies and
      comparing OSM3 results with those of an AVL 912 CO-oximeter. Retrospectively, we
      determined that the patient's specimens contained 6% SulfHb. There was an obvious
      deviation between standard OSM3 oxyhemoglobin fraction measurements and those
      obtained by using its service program-the effect of a high SulfHb content.

PMID- 8990241
TI  - Report of the Third Conference on Education in Clinical Chemistry.

PMID- 8990242
TI  - Evolution of the William Pepper Laboratory.

PMID- 8990243
TI  - Interference of nicotine metabolites in cotinine determination by RIA.

PMID- 8990244
TI  - Avoidance of false positives in PCR-based mRNA differential display during
      investigation of nonstandardized tissues or cells.

PMID- 8990245
TI  - Specificity of salivary thiocyanate as marker of cigarette smoking is not
      affected by alimentary sources.

PMID- 8990246
TI  - Measurement of maternal folate status and risk of neural tube defects.

PMID- 8990247
TI  - Different age-related trends of bone and nonbone forms of alkaline phosphatase in
      Chinese men and women.

PMID- 8990248
TI  - Data processing in CO-oximeters that use overdetermined systems.

PMID- 8990249
TI  - Chronic increased serum lipase in a patient with suspected pancreatic
      adenocarcinoma.

PMID- 8990250
TI  - Serum amyloid A remains at physiological concentrations in coronary
      atherosclerosis.

PMID- 8990251
TI  - Increased fatty acid-binding protein concentration in plasma of patients with
      chronic renal failure.

PMID- 8990252
TI  - Automated immunoassay of cardiac Troponin I in serum evaluated.

PMID- 8990253
TI  - Introduction and summary: 1996 NACB Standard of Laboratory Practice. National
      Academy of Clinical Biochemistry.

PMID- 8990254
TI  - Assessing fluid and electrolyte status in the newborn. National Academy of
      Clinical Biochemistry.
AB  - Fluid and electrolyte assessment during the first week of life is complicated by
      rapid changes in fluid and electrolyte balance during the transition from fetal
      to neonatal life and by the newborn's small size. A physiologic decrease in
      extracellular water volume, as well as a transient increase in serum potassium
      and transient decreases in plasma glucose and total plasma ionized calcium
      concentrations must be taken into account. In general, the more immature the
      newborn, the greater the changes that can be expected. The use of plasma
      creatinine as an indicator of glomerular filtration rate is limited because it is
      a function of maternal renal function at birth and because of non-steady-state
      conditions in the immediate postnatal period. Guidelines for monitoring schedules
      are provided on the basis of these physiologic considerations and the author's
      experience. Method of blood sampling and time to separation of serum are
      important considerations in interpreting results. Minimization of sample volume
      is critical to minimize blood transfusion requirements. Clinicians should be
      aware of the analytical error associated with these measurements in their own
      institutions. Reference ranges are provided.

PMID- 8990255
TI  - Standards of laboratory practice: evaluation of fetal lung maturity. National
      Academy of Clinical Biochemistry.
AB  - In this standard of laboratory practice I recommend guidelines for fetal lung
      maturity (FLM) testing. If possible, obtain a 10-mL uncontaminated sample by
      amniocentesis. Keep the amniotic fluid at 4 degrees C and mix well before
      testing. If centrifugation is required, strictly adhere to the protocol. Most
      laboratories should offer a rapid test, such as fluorescence polarization,
      phosphatidylglycerol, or foam stability index, daily on both a routine and
      emergency basis. Requests for lecithin/sphingomyelin ratio may be referred to a
      reference laboratory. Communicate immediately the results of any FLM test to the
      ordering location. The report should contain the result, sample contamination,
      and reference information. Separate reference intervals for diabetic patients are
      not recommended.

PMID- 8990256
TI  - Evaluation of the newborn's blood gas status. National Academy of Clinical
      Biochemistry.
AB  - Blood gas measurements and complementary, noninvasive monitoring techniques
      provide the clinician with information essential to patient assessment,
      therapeutic decision making, and prognostication. Blood gas measurements are as
      important for ill newborns as for other critically ill patients, but rapidly
      changing physiology, difficult access to arterial and mixed venous sampling
      sites, and small blood volumes present unique challenges. This paper discusses
      considerations for interpretation of blood gases in the newborn period. Blood gas
      measurements and noninvasive estimations provide important information about
      oxygenation. The general goals of oxygen therapy in the neonate are to maintain
      adequate arterial PaO2 and SaO2, and to minimize cardiac work and the work of
      breathing. Pulse oximetry and transcutaneous oxygen monitoring are
      extraordinarily useful techniques of estimating and noninvasively monitoring the
      neonate's oxygenation, but each method has limitations. Arterial blood gas
      determinations of pCO2 provide the most accurate determinations of the adequacy
      of alveolar ventilation, but capillary, transcutaneous, and end-tidal techniques
      are also useful. An approach to and examples of acid-base disorders are
      presented. Three hemoglobin variants relevant to the newborn are considered:
      fetal hemoglobin, carboxyhemoglobin, and methemoglobin. Blood gases obtained in
      the immediate perinatal period can help assess perinatal asphyxia, but particular
      attention must be paid to the sampling site, the time of life, and the possible
      and proven diagnoses.

PMID- 8990257
TI  - Therapeutic drug monitoring principles in the neonate. National Academy of
      CLinical Biochemistry.
AB  - Therapeutic drug monitoring in the newborn infant is necessary because dose
      requirements differ greatly from those for older children. These differences stem
      from major changes in kinetic disposition at the absorption, distribution, and
      elimination phases. The small blood volume of neonates makes them sensitive to
      iatrogenic blood loss. Similarly, the small size of these patients means that
      medication errors frequently lead to morbidity and even mortality. The clinical
      laboratory must set up strict, high-standard, carefully updated guidelines to
      ensure the safety of infants who need drug therapy at this very vulnerable phase
      of their lives.

PMID- 8990258
TI  - Assessing liver function and hyperbilirubinemia in the newborn. National Academy
      of Clinical Biochemistry.
AB  - In clinical practice, "liver function" is assessed by either measuring the
      concentration of substances produced by the hepatocyte, measuring the serum
      content of substances that are changed by hepatocyte damage, evaluating the serum
      concentrations of substances released from the cells as a result of injury,
      assessing the ability of the liver to perform a metabolic task such as
      conjugation or detoxification, or by measuring enzyme activity and substrate
      content of the cell and its organelles. After birth, with cessation of placental
      function, the neonatal liver must assume many different tasks. Distinct
      developmental sequences rapidly progress for numerous hepatic functions as the
      newborn adapts to its environment. This manuscript is an attempt to provide
      guidelines for the evaluation and management of the newborn infant when assessing
      liver function and hyperbilirubinemia. These guidelines, like all sets of
      guidelines, are only recommendations and do not substitute for good clinical
      judgment based upon the individual circumstances of each patient.

PMID- 8990259
TI  - Detection of intrauterine illicit drug exposure by newborn drug testing. National
      Academy of Clinical Biochemistry.
AB  - Identification of intrauterine drug-exposed newborns with toxicological screening
      may have benefits including close follow-up of the infant by both medical and
      social services. Applying specific written guidelines to select newborns for drug
      testing decreases bias and protects the physicians and hospitals involved. All
      drugs reported as positive should be confirmed by an appropriate second test.
      Urine and meconium testing are the best current options for identifying drug
      exposed neonates. Urine testing sensitivity is low because of problems
      encountered in urine collections and the high thresholds used in current urine
      assays. The disadvantage to meconium testing is the increased labor and time
      required to work with this material. Testing of newborn hair is unlikely to be
      widely used until technically less demanding assays become available. Testing of
      amniotic fluid or gastric lavage is still in the developmental stages. Adopting
      lower urine assay thresholds for newborn samples would increase sensitivity and
      would be an appropriate modification of current methodologies.

PMID- 8990260
TI  - Use of the laboratory in prediction of outcome in the high-risk newborn.
AB  - This paper reviews our ability to predict survival and neurodevelopmental outcome
      in the newborn period. Traditionally, prognosis is based on individual risk
      factors or disease states. The laboratory plays an important role in diagnosing
      some of these. For example, prenatal and newborn screening are important in the
      diagnosis of chromosomal abnormalities and inborn errors of metabolism. Abnormal
      bilirubin, glucose, and pH values in the newborn period are risk factors for
      death and abnormal neurodevelopment, and the degree of abnormality imparts
      additional information. Many newborns have multisystem disorders, and it is only
      when multiple variables are considered that outcome can be predicted. Three
      neonatal scores that incorporate multiple variables are discussed. Methodologic
      difficulties in determining outcome are reviewed and illustrated with survival
      and morbidity rates of very premature babies. The laboratory is one of many
      prognostic variables. The evaluation of how laboratory services are provided is
      difficult but important.

PMID- 8990261
TI  - Heme-coordinating analogs of lauric acid as inhibitors of fatty acid omega
      hydroxylation.
AB  - A series of omega-substituted fatty acids with potential heme-coordinating groups
      was synthesized as inhibitors of lauric acid omega-hydroxylation. The compounds
      were evaluated using liver microsomes from clofibrate (CF)-induced rats and an
      engineered expressed CYP4A1-derived fusion protein called f4A1. omega-Imidazolyl
      decanoic acid (compound 11) and omega-aminolauric acid (compound 7) were potent
      Type II ligands and potent inhibitors of lauric acid omega-hydroxylation in both
      CF-microsomes and f4A1. Replacing their terminal amino or imidazolyl groups with
      other potential iron-binding groups such as omega-methylsulfinyl-, omega-cyano-,
      omega-azido-, or omega-formamido all greatly reduced their potency as inhibitors
      of omega-hydroxylation and their affinity for cytochrome P450 as measured by Ks
      values. In CF-microsomes, inhibition of (omega-1)-hydroxylation of lauric acid by
      a homologous series of omega-imidazolyl-alkanoic acids varied only 2-fold but in
      the same incubations inhibition of omega-hydroxylation increased 22-fold upon
      going from C-8 to C-12. A similar dependence of binding affinity and inhibitory
      potency on chain length was also seen in the f4A1 system. In contrast, chain
      length had little effect on activity among n-alkylamines or N-alkylimidazoles
      lacking a carboxyl or other polar functional group, suggesting that 7, 11, and
      related bifunctional compounds interact with CYP4A1 in CF-microsomes and with
      f4A1 in a specific bidentate fashion. Imidazoles containing phenyl, benzyl, or
      phenylethyl substituents at N-1 interact less strongly than related N-alkyl
      imidazoles of similar carbon number and hydrophobicity, suggesting that the
      steric bulk and/or rigidity of the phenyl ring is not well accommodated in the
      active site.

PMID- 8990262
TI  - Structural interactions of the oligomycin sensitivity-conferring protein in the
      yeast ATP synthase.
AB  - The structure/function relationship of oligomycin sensitivity-conferring protein
      (OSCP), subunit 5 of the mitochondrial ATP synthase, from yeast Saccharomyces
      cerevisiae has been studied by a combination of genetic and biochemical methods.
      OSCP was studied by deletion mutagenesis of the N- and C-terminal regions by
      modifying the gene coding for OSCP. Two deletion mutations were made immediately
      downstream of the leader peptide of OSCP and five were made at the C-terminus.
      OSCP was functional with deletions of amino acids 3 to 17 (ND15) and of the last
      8 amino acids (CD8), while deletion of amino acids 3 to 31 (ND29) and the last 9
      amino acids (CD9) inactivated the ATP synthase, as determined by in vivo
      analysis. The deletion mutants were expressed in Escherichia coli, purified, and
      studied by in vitro reconstitution studies. Circular dichroism studies suggested
      that the mutant proteins, with the possible exception of ND29, were folded in a
      similar fashion as wild-type OSCP. Mutants ND15 and CD8 were able to reconstitute
      an oligomycin-sensitive ATPase complex, although not as well as wild-type OSCP,
      while ND29 and CD9 were completely ineffective. Binding studies of ND29 and CD9
      indicate that these mutants in OSCP were unable to bind to the membrane portion
      of the ATP synthase, F0, and these results were supported by competition binding
      studies. These results support the hypothesis that the N- and C-terminal regions
      of subunit 5 interact with F0 and suggest that the central region interacts with
      F1.

PMID- 8990263
TI  - ATP sulfurylase from filamentous fungi: which sulfonucleotide is the true
      allosteric effector?
AB  - Fungal ATP sulfurylase has been reported to be allosterically inhibited by 3'
      phosphoadenosine 5'-phosphosulfate (PAPS), the product of adenosine 5'
      phosphosulfate (APS) kinase, the second enzyme in the sulfate activation
      sequence. However, the affinity of ATP sulfurylase for its immediate product,
      APS, is 1000 times higher than that for PAPS. Moreover, each sulfurylase subunit
      contains two sulfonucleotide binding sites (the catalytic site and a C-terminal,
      APS kinase-like allosteric site). Consequently, the possibility that the
      cooperative effects were caused solely by trace levels of APS, or by APS acting
      in concert with PAPS could not be dismissed. To identify the true allosteric
      effector, the molybdolysis reaction kinetics in the absence and in the presence
      of APS kinase were compared. The rationale was that in the absence of APS kinase,
      submicromolar levels of APS would be generated from contaminating SO(2-)4 present
      in the assay components, while in the presence of APS kinase, any APS formed
      would be converted to PAPS. The results were as follows: In the presence of added
      APS kinase, the initial velocity versus [MgATP] or versus [MoO(2-)4] plots at 100
      microM PAPS were clearly sigmoidal as was the velocity versus [PAPS] plot at
      subsaturating substrate levels. Hill coefficients were in the range of 2 to 3.
      Also, low concentrations of S2O(2-)3offn inhibitor competitive with MoO(2-)4,
      activated the reaction at high PAPS and low substrate levels. These results are
      consistent with PAPS serving as a classical allosteric inhibitor. Although APS
      kinase should be superfluous to the molybdolysis reaction, the omission of this
      enzyme from assay mixtures resulted in rates that were higher, the same as, or
      lower than the corresponding "plus APS kinase" rates, (depending on the fixed
      level of substrates and PAPS). Additionally, the "minus APS kinase" velocity
      curves were less sigmoidal and, in some cases, nearly hyperbolic. The effect of
      APS kinase was shown to be catalytic in nature. If the data are analyzed in terms
      of the concerted transition (symmetry) model for allosteric enzymes, the
      cumulative experimental results indicate that PAPS is the true allosteric
      inhibitor of fungal ATP sulfurylase, binding preferentially to the T-state
      allosteric site (or to the allosteric site of the R state inducing the R --> T
      transition), while APS binds preferentially to the R state, probably as a
      competitive product inhibitor at the catalytic site. If it is assumed that
      occupancy of the allosteric site by any ligand that fits would induce the R --> T
      transition, then the results suggest that the allosteric site has evolved to have
      a higher affinity for PAPS than for APS (in contrast to real APS kinase).
      Computer-assisted simulations allowing for APS and PAPS binding to both the
      catalytic and regulatory sites of the hexameric enzyme yielded results that
      nearly duplicated the experimental curves.

PMID- 8990264
TI  - Mutagenesis of beta-V198 in the F1-ATPase of yeast Saccharomyces cerevisiae and
      its role in binding nucleotide.
AB  - Residue beta-V198 of the yeast mitchondrial F1-ATPase abuts the P-loop motif and
      the side chain is within 3.8 A of the nucleotide as shown in the crystal
      structure of the bovine ATPase [J. P. Abrahams, A. G. W. Leslie, R. Lutter, and
      J. E. Walker (1984) Nature 370,621-628]. This study has made and analyzed 17
      replacements of V198 to understand the importance of the side chain in the
      nucleotide binding site. In addition, a suppressor of V198S, beta-L390F, was
      studied in the presence of various replacements at position 198. In vivo and in
      vitro analyses indicate that the Val side chain is critical for forming a stable
      and active enzyme. Biochemical analysis of mitochondria isolated from the mutant
      strains indicates that amino acids with hydrophobic side chains are the most
      effective replacements. In addition, size is important, but a large side chain
      can be largely compensated for until the size reaches that of the Phe and Trp. A
      methyl group is the minimal side chain necessary for function, as the beta
      subunit is not stable in vivo with Gly at position 198. These results indicate
      that V198 forms critical hydrophobic interactions with the adenine ring of the
      nucleotide.

PMID- 8990265
TI  - A specific loss of growth hormone abolished sex-dependent expression of hepatic
      cytochrome P450 in dwarf rats: reversal of the profiles by growth hormone
      treatment.
AB  - A spontaneous dwarf rat derived from a colony of Sprague-Dawley (SD) strain has
      no detectable level of growth hormone (GH) in pituitary, although it contained
      other hormones like prolactin and ACTH. Hepatic profile of cytochrome P450 (P450)
      differed clearly between dwarf and normal SD rats. A male-specific form of P450,
      CYP2C11, was detected in dwarf male rat livers, while the level was one-third of
      the normal SD livers. This P450 was also detected in dwarf females. Other male
      specific CYP3A2 and CYP3A18 were also contained in both sexes of dwarf rats,
      whereas a female-specific form, CYP2C12, was not detectable in dwarf females.
      Phenobarbital-inducible CYP2B1 and CYP2B2 were constitutively expressed in dwarf
      rats, although substantially absent in normal SD rats. To assess the role of GH
      on hepatic P450 expression, GH was given to dwarf rats for 7 to 9 days. The
      intermittent injection (mimicking the male secretory pattern) resulted in the
      elevation of CYP2C11 to a level as observed in normal SD males. Continuous
      infusion of GH (mimicking the female secretory pattern) evoked CYP2C12 in livers
      of both sexes of dwarf rats, whereas the treatment decreased levels of CYP3A2,
      CYP3A18, and CYP2B1. These results clearly demonstrate that specific defect of
      GH, but not pituitary, cause the clear changes in hepatic P450 forms including
      sex-specific forms. The present study provides evidence further to strengthen the
      principal role of GH on the regulation of expression of P450 in rat livers.

PMID- 8990266
TI  - Effect of 5-hydroxytryptamine on sodium- and potassium-dependent adenosine
      triphosphatase and its reactivity toward ouabain.
AB  - Activity of vertebrate Na+,K+-ATPase was inhibited by 5-hydroxytryptamine.
      Inhibition was reversible, and activity could be restored by dilution of 5
      hydroxytryptamine (5HT). The ability of indole derivatives to inhibit depended on
      the presence of a net charge on the third atom of the indole C-3 side chain.
      Indoles with a net positive charge, such as 5HT, were stronger inhibitors than
      those with a net negative charge. Derivatives with a net charge of zero were not
      inhibitors. The ability of indole derivatives to inhibit Na+, K+-ATPase activity
      decreased in the order 5HT > tryptamine > tryptophanamide > tryptophol > N-acetyl
      5-methoxytryptamine > indole-3-acetic acid. Trp did not inhibit either ATPase or
      pNPPase activity. Charged indole derivatives also inhibited the pNPPase activity
      of Na+,K+-ATPase. 5HT and tryptophanamide were stronger inhibitors of pNPPase
      activity than indole-3-acetic acid. Binding of [3H]ouabain was inhibited by 5HT
      and tryptophanamide. Trp did not inhibit [3H]ouabain binding. The near
      equilibrium level of [3H]-ouabain binding in the presence of ATP, Mg2+, and Na+
      was decreased by 5HT in the manner characteristic of a competitive inhibitor.
      Enzyme-bound [3H]ouabain could be displaced by 5HT. 5HT was a complex mixed
      inhibitor of K+ with interactions at two sites, Tris was a competitive inhibitor
      with interactions at three sites, and ouabain was a simple noncompetitive
      inhibitor. The data are explained through a model indole binding site containing
      oppositely charged residues.

PMID- 8990267
TI  - [3H]-(R)-N6-Phenylisopropyladenosine agonist binding to the solubilized A1
      adenosine receptor from bovine epididymal spermatozoa.
AB  - The high-affinity agonist radioligand [3H]-(R)-N6-phenylisopropyladenosine ([3H]
      R-PIA) was used to investigate agonist A1 adenosine receptors interactions in
      soluble preparations from bovine spermatozoa. The digitonin-solubilized receptor
      shows a high-affinity state with a Kd of 5.32+/-1.17 nM and a Bmax of 460+/-33
      fmol/mg protein. The binding capacity, higher than that of the membrane-bound
      form, indicates that the soluble preparation is likely enriched with binding
      sites. In the presence of guanylyl-5'-imidodiphosphate (Gpp(NH)p), [3H]-R-PIA
      binds to the soluble receptor with a Kd of 7.97+/-1.44 nM and a Bmax of 400.8+/
      27 fmol/mg protein. The radioligand rapidly dissociates with a K(-1) of 0.125
      min(-1) although specific [3H]-R-PIA is still found in solubilized A1 receptor.
      The A1 agonist N6-cyclopentyladenosine differentiates two affinity states,
      whereas Gpp(NH)p shifts the agonist curve to the right and all the receptors are
      in the low-affinity state. In the presence of NaCl, the agonist still recognizes
      two affinity states with a lower affinity than that observed in the absence of
      NaCl. Analyses of sedimentation profiles show the existence of a population of A1
      receptors tightly coupled to Gi, the pertussin toxin-sensitive component of the G
      protein family.

PMID- 8990268
TI  - Expression and inducibility of cytochrome P450 3A9 (CYP3A9) and other members of
      the CYP3A subfamily in rat liver.
AB  - Quantitative reverse-transcriptase polymerase chain reaction was used to
      determine the content of mRNA derived from four CYP3A genes (CYP3A2, CYP3A9,
      CYP3A18, and CYP3A23) in rat liver. CYP3A2 and CYP3A9 gene expression was age-
      and sex-dependent, whereas CYP3A18 and CYP3A23 mRNA were observed before and
      after puberty at fairly constant levels that were about 20% higher in males than
      in females. CYP3A9 mRNA was detected only in adult rats, with a nearly twofold
      higher expression in females. CYP3A9 induction was different from other CYP3A
      isoenzymes, since phenobarbital was a more effective inducer than dexamethasone
      and clotrimazole. The results presented for CYP3A23 are those anticipated for
      CYP3A1, which may be an allelic variant of CYP3A23 not detected in these
      experiments. These data show that rat CYP3A genes are variably expressed
      depending on age, sex, or inducer type.

PMID- 8990271
TI  - Betaine-aldehyde dehydrogenase from amaranth leaves efficiently catalyzes the NAD
      dependent oxidation of dimethylsulfoniopropionaldehyde to
      dimethylsulfoniopropionate.
AB  - Many flowering plants accumulate the compatible osmolyte glycine betaine in
      response to osmotic stress, in certain cases together with its sulfonium analog 3
      dimethylsulfoniopropionate (DMSP). Compared to glycine betaine, this DMSP
      accumulation appears to be an evolutionary novelty. The final step in the
      synthesis of glycine betaine and DMSP is oxidation of the corresponding aldehyde,
      betaine aldehyde or 3-dimethylsulfoniopropionaldehyde (DMSPald). Leaves of
      amaranth (Amaranthus hypochondriacus L.) accumulate glycine betaine but do not
      produce detectable amounts of DMSP. These leaves contain a betaine-aldehyde
      dehydrogenase (BADH) that catalyzes the final step in glycine betaine synthesis.
      Here we report that this enzyme efficiently catalyzes the oxidation of DMSPald.
      On the basis of Vmax/Km values, DMSPald is a better substrate for amaranth BADH
      than betaine aldehyde itself. The kinetic mechanism followed by amaranth BADH at
      low concentrations of DMSPald is similar to that with betaine aldehyde; as
      determined from initial velocity, product, dead-end, and substrate inhibition
      studies, it is a steady-state bi bi with ordered addition of substrates and
      random release of products. Like betaine aldehyde, DMSPald is inhibitory at high
      concentrations, at which a slower alternate route of substrate addition takes
      place. Our results indicate that the evolution of DMSP biosynthesis in flowering
      plants could have been facile in that it required no new aldehyde dehydrogenase;
      BADH may simply have been recruited for a novel function.

PMID- 8990270
TI  - Changes of energy metabolism induced by 1-methyl-4-phenylpyridinium (MPP+)
      related compounds in rat pheochromocytoma PC12 cells.
AB  - We examined effects of three structurally related pyridinium compounds, 1-methyl
      4-phenylpyridinium (MPP+), paraquat, and 1-methyl-4-(4'-nitrophenyl) pyridinium
      (analog 1), on the energy metabolism in pheochromocytoma PC12 cells. MPP+
      inhibited the intracellular NADH oxidation by the mitochondrial respiratory
      chain, judging from the decrease of the cytosolic NAD+/NADH ratio. Paraquat
      enhanced the oxidation of NADH and decreased intracellular ATP more than MPP+.
      The inhibition of the mitochondrial respiration by MPP+ was partially compensated
      by enhanced glycolysis, while paraquat inhibited glycolysis at the level of
      hexokinase probably due to the intracellular production of oxygen radicals.
      Analog 1 moderately enhanced glycolysis, moderately increased a cytosolic ratio
      of NAD+/NADH, and caused only a slight decline of intracellular ATP. Paraquat was
      the most cytotoxic of the three compounds. Thus, the three structurally related
      compounds, MPP+, paraquat, and analog 1, showed different effects on the
      mitochondrial respiratory chain and the glycolytic pathway in PC 12 cells. Their
      properties found in the cells well reflected those obtained by using bovine heart
      submitochondrial particles.

PMID- 8990272
TI  - Vibrio harveyi NADPH:FMN oxidoreductase: preparation and characterization of the
      apoenzyme and monomer-dimer equilibrium.
AB  - A rapid chromatography method was developed for the preparation of apoenzyme of
      Vibrio harveyi NADPH:FMN oxidoreductase with > or =80% yields. The apoenzyme
      bound one FMN per enzyme monomer with a dissociation constant of 0.2 microM at 23
      degrees C. The reconstituted holoenzyme was catalytically as active as the native
      enzyme. FMN binding resulted in 87 and 92% of quenching of protein and flavin
      fluorescence, respectively, indicating a conformational difference between the
      apoprotein and the holoenzyme. Neither riboflavin nor FAD showed any appreciable
      binding to the cofactor site of the apoenzyme but both flavins were active
      substrates for the FMN-containing holoenzyme. 2-ThioFMN bound to the cofactor
      site of the apoenzyme with an affinity similar to that for FMN binding. The
      holoenzyme reconstituted with 2-thioFMN showed a 509-nm absorption peak, which
      represents a 19-nm red shift from the corresponding peak of the free flavin, and
      was catalytically active in using either FMN or 2-thioFMN as a substrate. The
      holoenzyme showed a concentration dependence in molecular sieve chromatography
      corresponding to higher apparent molecular weights at higher concentrations. Both
      the holoenzyme and the apoenzyme was shown at 4 degrees C by equilibrium
      ultracentrifugation to undergo dimerization with dissociation constants of 1.8
      and 3.3 microM, respectively.

PMID- 8990274
TI  - L-Malate dehydrogenase from Pseudomonas stutzeri: purification and
      characterization.
AB  - L-Malate dehydrogenase (MDH) from Pseudomonas stutzeri was purified to
      homogeneity by a two-step procedure comprising anion-exchange chromatography and
      affinity chromatography on immobilized anthraquinone alpha-ketocarboxyl
      biomimetic dye. The enzyme has molecular mass of 66,500 Da and consists of two
      identical subunits of molecular mass of approximately 34,000 Da. Initial
      velocity, product inhibition, and binding studies were consistent with an ordered
      Bi-Bi mechanism for the enzyme action and the formation of a ternary complex. The
      enzyme is susceptible to activation and inhibition by its substrates.
      Thermodynamic analysis and kinetic inhibition studies were performed for
      determining basic equilibrium and kinetic constants. Malate dehydrogenase was
      covalently inactivated by a dichlorotriazine dye, Vilmafix Blue A-R (VBAR). The
      inactivation process follows first-order kinetics, and the results from kinetic
      analysis suggested the formation of a noncovalent enzyme-dye complex prior to the
      covalent reaction, with Kd 84.6 microM and a maximum rate constant 0.16 min(-1).
      The enzyme inactivation process was partially inhibited by substrates and
      inhibitors. Quantitatively inactivated MDH contained approximately 1 mole of dye
      per mole of enzyme subunit. The denatured enzyme contains 10 sulfhydryl groups
      per subunit, as shown after reaction with 5,5'-dithio-bis-(2-nitrobenzoic acid),
      of which 5 can be titrated also in the native enzyme, exhibiting time-dependent
      reactivity. One sulfhydryl group is located in the coenzyme binding site. This
      study shows that the physical and catalytic properties of P. stutzeri MDH
      strongly resemble those of the mitochondrial eukariotic enzyme. This finding
      strengthens the existing view that, in the evolution process, the mitochondrial
      MDH might have appeared before the cytoplasmic.

PMID- 8990273
TI  - Inhibition of protein kinase C-dependent noradrenaline release by wortmannin in
      PC12 cells.
AB  - Wortmannin is a specific phosphatidylinositol 3-kinase inhibitor, and it inhibits
      secretion in many cell types. Previously we reported that high K+ and external
      ATP stimulated a Ca2+ influx and [3H]-noradrenaline ([3H]NA) release from rat
      pheochromocytoma cell line 12 (PC12) cells in the presence of extracellular
      CaCl2. Addition of phorbol 12-myristate 13-acetate (PMA) stimulated [3H]NA
      release by itself and enhanced the maximal responses of high K+ and ATP. In this
      study, we investigated the effects of wortmannin on NA release from PC12 cells.
      Wortmannin inhibited the [3H]NA release induced by high K+ and ATP, and the
      stimulatory effects of PMA, in a dose-dependent manner. Wortmannin caused 50%
      inhibition of high K+-induced [3H]NA release at a concentration of 2.78+/-0.68
      microM (n = 5). The increased cytosolic free Ca2+ concentrations ([Ca2+]i),
      induced by ATP, were not inhibited by wortmannin. Wortmannin inhibited PMA
      induced phosphorylation of a 80-kDa protein in the cytosol fraction of PC12
      cells. Calphostin C, a specific protein kinase C inhibitor, also inhibited high
      K+-, ATP-, and PMA-induced NA release, and the phosphorylation of the 80-kDa
      protein induced by PMA. Mastoparan, an amphiphilic tetradecapeptide from wasp
      venom, stimulated NA release in the presence or absence of extracellular CaCl2.
      Neither wortmannin nor calphostin C inhibited the NA release induced by
      mastoparan. These findings suggest that wortmannin inhibits the PKC-dependent
      pathway, not [Ca2+]i mobilization, resulting in the inhibition of NA release from
      PC12 cells.

PMID- 8990275
TI  - Lucigenin (bis-N-methylacridinium) as a mediator of superoxide anion production.
AB  - Lucigenin (bis-N-methylacridinium) (Luc2+) has frequently been used for the
      luminescent detection of O2-. In fact, the pathway leading to this luminescence
      requires univalent reduction of Luc2+ to LucH.+ followed by formation of an
      unstable dioxetane by reaction of LucH.+ with O2-. It is now shown that LucH.+
      rapidly autooxidizes and so produces O2-. Luc2+ can thus mediate O2- production
      in systems, such as glucose plus glucose oxidase, in which there is ordinarily no
      O2- production. Luc2+ luminescence can thus be used as the basis for assaying
      superoxide dismutase activity but should not be used for measuring, or even
      detecting, O2-.

PMID- 8990276
TI  - Early redox changes during rat thymocyte apoptosis.
AB  - Methylprednisolone (glucocorticoid hormone, MPS), etoposide (epipodophyllotoxin
      inhibitor of a topoisomerase II), and thapsigargin (inhibitor of the endoplasmic
      reticular Ca2+-ATPase) were used as apoptosis-inducing agents in rat thymocytes.
      Early redox changes were determined during the early phase of induced apoptosis.
      The three agents induced apoptosis as assessed by DNA laddering after agarose gel
      electrophoresis and by quantitative DNA fragmentation. Intracellular H2O2
      steadystate concentrations after 30 min of incubation were 40, 48, 25, and 75 nM
      for control and MPS-, etoposide-, and thapsigargin-treated thymocytes,
      respectively. After 30 min of MPS and thapsigargin exposure, increased DCFH
      oxidation was clear compared with control cells, but no increase in
      dichlorofluorescein (DCF) was observed in etoposide-treated thymocytes. DCF
      fluorescence correlated linearly with the intracellular H2O2 concentration after
      30 min of incubation. The amounts of thiobarbituric acid-reactive substances
      produced after 3 h of incubation and expressed as pmol/mg protein were 105+/-23,
      120+/-18, 350+/-17, and 98+/-24 pmol/mg protein for untreated and MPS-,
      thapsigargin-, and etoposide-treated thymocytes, respectively. Common and marked
      reductions in intracellular glutathione of 46, 73, 58, and 39% were observed
      after 2 h of incubation with MPS-, thapsigargin-, and etoposide-treated cells and
      in untreated cells, respectively. A simultaneous increase in oxidized
      glutathione, compared with untreated cells, was evident in MPS (66%) and was
      stronger in thapsigargin-exposed cells (250%). A 55% decrease in GSSG in
      etoposide-treated cells was found. It is concluded that redox changes occur
      during the early phase of induced apoptosis in rat thymocytes and are not always
      associated with an oxidative stress. Rather, this situation is closely related
      with the type of stimuli.

PMID- 8990277
TI  - Characterization of L-glutamine:D-fructose-6-phosphate amidotransferase from an
      extreme thermophile Thermus thermophilus HB8.
AB  - Glucosamine-6-phosphate synthase from the extremophile Thermus thermophilus
      (GlmSth) was purified to homogeneity from an Escherichia coli overproducer. The
      homodimeric enzyme exhibits an optimum activity at 70 degrees C with a half-life
      of 90 min at 80 degrees C. Dissociation experiments in guanidinium chloride and
      urea are consistent with the absence of catalytic activity of the monomer.
      Differential scanning microcalorimetry analysis of GlmSth revealed an
      irreversible denaturation process with a delta(H)cal = 257 kcal x mol(-1) and Tm
      = 82.6 degrees C. Antigenic cross-reaction with GlmSth was observed with the E.
      coli enzyme using monoclonal antibodies (mAbs) specific for linear epitopes of
      the glutamine binding domain. However, no cross-reactivity was observed with an
      mAb specific for a native conformation of the E. coli enzyme. The inhibition
      constants of 6-diazo-5-oxo-L-norleucine and methoxyfumaroyl-L-2,3
      diaminopropionic acid, potent glutamine site-directed affinity labels of the E.
      coli enzyme, were reduced by 2 to 3 orders of magnitude when tested on GlmSth,
      whereas the properties of 2-amino-2-deoxyglucitol-6P, a potent competitive
      inhibitor of the fructose-6P site, remained unaffected. These data, combined with
      its unexpected resistance to limited proteolysis, are consistent with an increase
      in the structural constraint of the thermophile enzyme vs its mesophilic
      counterpart.

PMID- 8990278
TI  - Inhibition of monoamine oxidase A by beta-carboline derivatives.
AB  - beta-Carbolines are endogenous inhibitors of monoamine oxidase (MAO). The
      interaction of nine beta-carboline derivatives and four 3,4-dihydro forms with
      purified MAO A was investigated. All the compounds tested were reversible
      competitive inhibitors selective for MAO A, in agreement with previous studies on
      membrane preparations. The oxidation of kynuramine by MAO A in the presence of
      the more effective inhibitors showed a lag period before reaching the steady
      state. In general, the 1-methyl and 7-methoxy substituents increased the potency.
      Harmine, 2-methylharminium, 2,9-dimethylharminium, and harmaline were the most
      effective inhibitors of the purified MAO A, with low Ki values of 5, 69, 15, and
      48 nM, respectively. The inhibitors interacted with the covalently bound flavin
      to induce distinct spectral changes, the magnitude of which correlated with the
      efficacy of the inhibition. The more effective inhibitors could be in situ
      inhibitors of MAO A.

PMID- 8990279
TI  - Shedding light on anaerobic benzene ring degradation: a process unique to
      prokaryotes?

PMID- 8990280
TI  - nfi, the gene for endonuclease V in Escherichia coli K-12.
AB  - Endonuclease V is specific for single-stranded DNA or for duplex DNA that
      contains uracil or that is damaged by a variety of agents (B. Demple and S. Linn,
      J. Biol. Chem. 257:2848-2855, 1982). Thus, it may be a versatile DNA repair
      enzyme. The protein was purified to apparent homogeneity, and from its N-terminal
      sequence, its gene, nfi, was identified. nfi is immediately downstream of hemE,
      at kb 4208 (90.4 min) on the current chromosomal map of Escherichia coli K-12.
      This region was cloned, and plasmid insertion and deletion mutants were used to
      study its molecular organization. Although nfi is the third of four closely
      spaced, codirectional genes, it is expressed independently.

PMID- 8990281
TI  - Contribution of horizontal gene transfer and deletion events to development of
      distinctive patterns of fimbrial operons during evolution of Salmonella
      serotypes.
AB  - Only certain serotypes of Salmonella represent 99% of all human clinical
      isolates. We determined whether the phylogenetic distribution of fimbrial operons
      would account for the host adaptations observed for Salmonella serotypes. We
      found that three fimbrial operons, fim, lpf, and agf, were present in a lineage
      ancestral to Salmonella. While the fim and agf fimbrial operons were highly
      conserved among all Salmonella serotypes, sequence analysis suggested that the
      lpf operon was lost from many distantly related lineages. As a consequence, the
      distribution of the lpf operon cannot be explained easily and may be a
      consequence of positive and negative selection in different hosts for the
      presence of these genes. Two other fimbrial operons, sef and pef, each entered
      two distantly related Salmonella lineages and each is present only in a small
      number of serotypes. These results show that horizontal gene transfer and
      deletion events have created unique combinations of fimbrial operons among
      Salmonella serotypes. The presence of sef and pef correlated with serotypes
      frequently isolated from common domesticated animals.

PMID- 8990282
TI  - Purification and characterization of VSH-1, a generalized transducing
      bacteriophage of Serpulina hyodysenteriae.
AB  - Serpulina hyodysenteriae B204 cells treated with mitomycin (20 microg of
      mitomycin/ml of culture broth) lysed and released bacteriophages. Bacteriophage
      particles, precipitated by using polyethylene glycol and purified by CsC1 density
      gradient ultracentrifugation, had a buoyant density of 1.375 g/cm3 and consisted
      of a head (45-nm diameter) and an ultrastructurally simple (noncontractile) tail
      (64 by 9 nm) composed of at least 13 proteins with molecular masses ranging
      between 13 and 101 kDa. The purified bacteriophage has been designated VSH-1 (VSH
      for virus of S. hyodysenteriae). VSH-1 was incapable of lytic growth on any of
      five intestinal spirochete strains, representing three Serpulina species. VSH-1
      nucleic acid was determined to be approximately 7.5 kb in size and to be linear,
      double-stranded DNA based on differential staining with acridine orange, DNase I
      sensitivity, electrophoretic mobility, and contour length as measured by electron
      microscopy. Phage DNA digested by the restriction enzymes SspI, AseI, EcoRV, and
      AflII gave electrophoretic banding patterns nearly identical to those of digested
      chromosomal DNA from S. hyodysenteriae. Additionally, VSH-1 DNA fragments
      hybridized with probes complementary to S. hyodysenteriae chromosomal genes nox
      and flaA1. When purified bacteriophages induced from cultures of S.
      hyodysenteriae A203 (deltaflaA1 593-762::cat) were added to growing cells of
      strain A216 (deltanox 438-760::kan), transductants (Cmr Kmr) were obtained at a
      frequency of 1.5 x l0(-6) per phage particle (enumerated by electron microscopy).
      These findings indicate that induced VSH-1 virions package DNA of S.
      hyodysenteriae and are capable of transferring host genes between cells of that
      spirochete. To our knowledge, this is the first report of genetic transduction of
      a spirochete.

PMID- 8990284
TI  - The action in vivo of glycine betaine in enhancement of tolerance of
      Synechococcus sp. strain PCC 7942 to low temperature.
AB  - The cyanobacterium Synechococcus sp. strain PCC 7942 was transformed with the
      codA gene for choline oxidase from Arthrobacter globiformis under the control of
      a constitutive promoter. This transformation allowed the cyanobacterial cells to
      accumulate glycine betaine at 60 to 80 mM in the cytoplasm. The transformed cells
      could grow at 20 degrees C, the temperature at which the growth of control cells
      was markedly suppressed. Photosynthesis of the transformed cells at 20 degrees C
      was more tolerant to light than that of the control cells. This was caused by the
      enhanced ability of the photosynthetic machinery in the transformed cells to
      recover from low-temperature photoinhibition. In darkness, photosynthesis of the
      transformed cells was more tolerant to low temperature such as 0 to 10 degrees C
      than that of the control cells. In parallel with the improvement in the ability
      of the transformed cells to tolerate low temperature, the lipid phase transition
      of plasma membranes from the liquid-crystalline state to the gel state shifted
      toward lower temperatures, although the level of unsaturation of the membrane
      lipids was unaffected by the transformation. These findings suggest that glycine
      betaine enhances the tolerance of photosynthesis to low temperature.

PMID- 8990283
TI  - Identification and characterization of hydrogen peroxide-sensitive mutants of
      Escherichia coli: genes that require OxyR for expression.
AB  - Escherichia coli produces an inducible set of proteins that protect the cell from
      exogenous peroxide stress. A subset of these genes is induced by hydrogen
      peroxide and is controlled at the transcriptional level by the OxyR protein. To
      identify additional genes involved in protection from hydrogen peroxide, a
      library of random transcriptional fusions of lambda(plac)Mu53 was screened for
      hydrogen peroxide sensitivity and 27 such mutants were identified. These fusions
      were transduced into nonlysogenic strains to ensure that the phenotypes observed
      were the result of a single mutation. The mutants were grouped into three classes
      based on the expression of the lacZ fusion during growth in oxyR+ and deltaoxyR
      backgrounds. The expression of the lacZ fusion in 8 mutants was independent of
      OxyR, 10 mutants required OxyR for expression, and 6 mutants showed reduced
      levels of expression in the presence of OxyR. OxyR dependence varied from 2- to
      50-fold in these mutants. The OxyR-dependent phenotype was complemented by a
      plasmid-borne copy of oxyR gene in all mutants. Three mutants exhibited dual
      regulation by OxyR and RpoS. We sequenced the fusion junctions of several of
      these mutants and identified the genetic loci responsible for the hydrogen
      peroxide-sensitive (hps) phenotype. In this study, we report the identification
      of several genes that require OxyR for expression, including hemF (encoding
      coproporphyrinogen III oxidase), rcsC (encoding a sensor-regulator protein of
      capsular polysaccharide synthesis genes), and an open reading frame, f497, that
      is similar to arylsulfatase-encoding genes.

PMID- 8990285
TI  - Sequencing of heat shock protein 70 (DnaK) homologs from Deinococcus
      proteolyticus and Thermomicrobium roseum and their integration in a protein-based
      phylogeny of prokaryotes.
AB  - The 70-kDa heat shock protein (hsp70) sequences define one of the most conserved
      proteins known to date. The hsp70 genes from Deinococcus proteolyticus and
      Thermomicrobium roseum, which were chosen as representatives of two of the most
      deeply branching divisions in the 16S rRNA trees, were cloned and sequenced.
      hsp70 from both these species as well as Thermus aquaticus contained a large
      insert in the N-terminal quadrant, which has been observed before as a unique
      characteristic of gram-negative eubacteria and eukaryotes and is not found in any
      gram-positive bacteria or archaebacteria. Phylogenetic analysis of hsp70
      sequences shows that all of the gram-negative eubacterial species examined to
      date (which includes members from the genera Deinococcus and Thermus, green
      nonsulfur bacteria, cyanobacteria, chlamydiae, spirochetes, and alpha-, beta-,
      and gamma-subdivisions of proteobacteria) form a monophyletic group (excluding
      eukaryotic homologs which are derived from this group via endosybitic means)
      strongly supported by the bootstrap scores. A closer affinity of the Deinococcus
      and Thermus species to the cyanobacteria than to the other available gram
      negative sequences is also observed in the present work. In the hsp7O trees, D.
      proteolyticus and T. aquaticus were found to be the most deeply branching species
      within the gram-negative eubacteria. The hsp70 homologs from gram-positive
      bacteria branched separately from gram-negative bacteria and exhibited a closer
      relationship to and shared sequence signatures with the archaebacteria. A
      polyphyletic branching of archaebacteria within gram-positive bacteria is
      strongly favored by different phylogenetic methods. These observations differ
      from the rRNA-based phylogenies where both gram-negative and gram-positive
      species are indicated to be polyphyletic. While it remains unclear whether parts
      of the genome may have variant evolutionary histories, these results call into
      question the general validity of the currently favored three-domain dogma.

PMID- 8990286
TI  - The HflB protease of Escherichia coli degrades its inhibitor lambda cIII.
AB  - The cIII protein of bacteriophage lambda is known to protect two regulatory
      proteins from degradation by the essential Escherichia coli protease HflB (also
      known as FtsH), viz., the lambda cII protein and the host heat shock sigma factor
      sigma32. lambda cIII, itself an unstable protein, is partially stabilized when
      the HflB concentration is decreased, and its half-life is decreased when HflB is
      overproduced, strongly suggesting that it is degraded by HflB in vivo. The in
      vivo degradation of lambda cIII (unlike that of sigma32) does not require the
      molecular chaperone DnaK. Furthermore, the half-life of lambda cIII is not
      affected by depletion of the endogenous ATP pool, suggesting that lambda cIII
      degradation is ATP independent (unlike that of lambda cII and sigma32). The
      lambda cIII protein, which is predicted to contain a 22-amino-acid amphipathic
      helix, is associated with the membrane, and nonlethal overproduction of lambda
      cIII makes cells hypersensitive to the detergent sodium dodecyl sulfate. This
      could reflect a direct lambda cIII-membrane interaction or an indirect
      association via the membrane-bound HflB protein, which is known to be involved in
      the assembly of certain periplasmic and outer membrane proteins.

PMID- 8990287
TI  - Dissection of the transcription machinery for housekeeping genes of
      Bradyrhizobium japonicum.
AB  - By using a PCR approach, the Bradyrhizobium japonicum sigA gene, which encodes
      the primary RNA polymerase sigma factor, sigma80, was cloned and its nucleotide
      sequence was established. The deduced protein is highly homologous to the SigA
      protein of Rhizobium meliloti (72% amino acid sequence identity) but less so to
      RpoD of Escherichia coli (51% identity). Well conserved is the C-terminal end of
      the protein, which is probably involved in promoter recognition and binding of
      the RNA polymerase core enzyme. A remarkable feature of the primary sequence is
      an alanine- and proline-rich segment of 24 amino acids between conserved regions
      1 and 2, which might function as an interdomain linker. We purified the B.
      japonicum RNA polymerase holoenzyme. One of the subunits had an apparent
      molecular mass of 90 kDa and corresponded to the sigA gene product, as judged by
      N-terminal amino acid sequencing. The purified RNA polymerase was used in an in
      vitro transcription system to determine the transcription start sites of the rrn
      and groESL4 operons. They were identical to those previously identified in vivo.
      The rrn promoter was cloned upstream of a rho-independent terminator, yielding a
      transcript of about 240 bases. This served as a suitable template to analyze
      promoter activity. Then mutant derivatives of the rrn promoter were constructed
      and tested in in vitro transcription experiments. Several base pairs essential
      for promoter activity were thus identified. The results suggest that the well
      characterized -35/-10 promoter class is predominantly used in B. japonicum for
      the expression of "housekeeping" genes.

PMID- 8990289
TI  - Homeostatic regulation of intracellular hydrogen peroxide concentration in
      aerobically growing Escherichia coli.
AB  - The exponential phase of aerobic growth is associated with risk of endogenous
      oxidative stress in which cells need to cope with an approximately 10-fold
      increase in the rate of H2O2 generation. We addressed this issue by studying the
      regulation of the intracellular concentration of H2O2 in aerobically growing
      Escherichia coli. Intracellular H2O2 was kept at an almost constant steady-state
      value of approximately 0.2 microM (variation, less than twofold) over a broad
      range of cell densities in rich medium. This regulation was achieved in part by a
      transient increase in the OxyR-dependent transcription of the catalase gene katG
      (monitored by using a katG::lacZ operon fusion) during exponential growth,
      directly correlated with the increased rate of H2O2 generation. The OxyR
      regulated alkyl hydroperoxide reductase encoded by ahpFC did not detectably
      affect H2O2 or catalase activity levels. Induction of katG, ahpFC, and perhaps
      other genes prevented the accumulation of oxidatively modified lipids but may not
      have protected DNA: the spontaneous mutation rate was significantly increased in
      both wild-type and delta(oxy)R strains during exponential growth compared to that
      in these strains during lag or stationary phases. Strains lacking oxyR showed
      throughout growth an 8- to 10-fold-higher frequency of spontaneous mutation than
      was seen for wild-type bacteria. The ahpdelta5 allele also had a mutator effect
      half of that of delta(oxy)R in exponential and stationary phases and equal to
      that of deltaoxyR in lag phase, perhaps by affecting organic peroxide levels.
      These results show that oxyR-regulated catalase expression is not solely an
      emergency response of E. coli to environmental oxidative stress, but also that it
      mediates a homeostatic regulation of the H2O2 produced by normal aerobic
      metabolism. The activation of the oxyR regulon in this process occurs at much
      lower levels of H2O2 (approximately 10(-7)M) than those reported for oxyR
      activation by exogenous H2O2 (approximately 10(-5) M).

PMID- 8990288
TI  - Characterization of catechol catabolic genes from Rhodococcus erythropolis 1CP.
AB  - The biochemical characterization of the muconate and the chloromuconate
      cycloisomerases of the chlorophenol-utilizing Rhodococcus erythropolis strain 1CP
      previously indicated that efficient chloromuconate conversion among the gram
      positive bacteria might have evolved independently of that among gram-negative
      bacteria. Based on sequences of the N terminus and of tryptic peptides of the
      muconate cycloisomerase, a fragment of the corresponding gene has now been
      amplified and used as a probe for the cloning of catechol catabolic genes from R.
      erythropolis. The clone thus obtained expressed catechol 1,2-dioxygenase,
      muconate cycloisomerase, and muconolactone isomerase activities. Sequencing of
      the insert on the recombinant plasmid pRER1 revealed that the genes are
      transcribed in the order catA catB catC. Open reading frames downstream of catC
      may have a function in carbohydrate metabolism. The predicted protein sequence of
      the catechol 1,2-dioxygenase was identical to the one from Arthrobacter sp.
      strain mA3 in 59% of the positions. The chlorocatechol 1,2-dioxygenases and the
      chloromuconate cycloisomerases of gram-negative bacteria appear to be more
      closely related to the catechol 1,2-dioxygenases and muconate cycloisomerases of
      the gram-positive strains than to the corresponding enzymes of gram-negative
      bacteria.

PMID- 8990290
TI  - cse15, cse60, and csk22 are new members of mother-cell-specific sporulation
      regulons in Bacillus subtilis.
AB  - We report on the characterization of three new transcription units expressed
      during sporulation in Bacillus subtilis. Two of the units, cse15 and cse60, were
      mapped at about 123 degrees and 62 degrees on the genetic map, respectively.
      Their transcription commenced around h 2 of sporulation and showed an absolute
      requirement for sigmaE. Maximal expression of both cse15 and cse60 further
      depended on the DNA-binding protein SpoIIID. Primer extension results revealed 
      10 and -35 sequences upstream of the cse15 and cse60 coding sequences very
      similar to those utilized by sigmaE-containing RNA polymerase. Alignment of these
      and other regulatory regions led to a revised consensus sequence for sigmaE
      dependent promoters. A third transcriptional unit, designated csk22, was
      localized at approximately 173 degrees on the chromosome. Transcription of csk22
      was activated at h 4 of sporulation, required the late mother-cell regulator
      sigmaK, and was repressed by the GerE protein. Sequences in the csk22 promoter
      region were similar to those of other sigmaK-dependent promoters. The cse60 locus
      was deduced to encode an acidic product of only 60 residues. A 37.6-kDa protein
      apparently encoded by cse15 was weakly related to the heavy chain of myosins, as
      well as to other myosin-like proteins, and is predicted to contain a central, 100
      residue-long coiled-coil domain. Finally, csk22 is inferred to encode a 18.2-kDa
      hydrophobic product with five possible membrane-spanning helices, which could
      function as a transporter.

PMID- 8990291
TI  - Nucleotide sequences and regulational analysis of genes involved in conversion of
      aniline to catechol in Pseudomonas putida UCC22(pTDN1).
AB  - A 9,233-bp HindIII fragment of the aromatic amine catabolic plasmid pTDN1,
      isolated from a derivative of Pseudomonas putida mt-2 (UCC22), confers the
      ability to degrade aniline on P. putida KT2442. The fragment encodes six open
      reading frames which are arranged in the same direction. Their 5' upstream region
      is part of the direct-repeat sequence of pTDN1. Nucleotide sequence of 1.8 kb of
      the repeat sequence revealed only a single base pair change compared to the known
      sequence of IS1071 which is involved in the transposition of the chlorobenzoate
      genes (C. Nakatsu, J. Ng, R. Singh, N. Straus, and C. Wyndham, Proc. Natl. Acad.
      Sci. USA 88:8312-8316, 1991). Four open reading frames encode proteins with
      considerable homology to proteins found in other aromatic-compound degradation
      pathways. On the basis of sequence similarity, these genes are proposed to encode
      the large and small subunits of aniline oxygenase (tdnA1 and tdnA2,
      respectively), a reductase (tdnB), and a LysR-type regulatory gene (tdnR). The
      putative large subunit has a conserved [2Fe-2S]R Rieske-type ligand center. Two
      genes, tdnQ and tdnT, which may be involved in amino group transfer, are
      localized upstream of the putative oxygenase genes. The tdnQ gene product shares
      about 30% similarity with glutamine synthetases; however, a pUC-based plasmid
      carrying tdnQ did not support the growth of an Escherichia coli glnA strain in
      the absence of glutamine. TdnT possesses domains that are conserved among
      amidotransferases. The tdnQ, tdnA1, tdnA2, tdnB, and tdnR genes are essential for
      the conversion of aniline to catechol.

PMID- 8990293
TI  - Proliferation of mutators in A cell population.
AB  - A Lac- strain of Escherichia coli that reverts by the addition of a G to a G-G-G
      G-G-G sequence was used to study the proliferation of mutators in a bacterial
      culture. Selection for the Lac+ phenotype, which is greatly stimulated in
      mismatch repair-deficient strains, results in an increase in the percentage of
      mutators in the selected population from less than 1 per 100,000 cells to 1 per
      200 cells. All the mutators detected were deficient in the mismatch repair
      system. Mutagenesis results in a similar increase in the percentage of mutators.
      Mutagenesis combined with a single selection can result in a population of more
      than 50% mutators when a sample of several thousand cells is grown out and
      selected. Mutagenesis combined with two or more successive selections can
      generate a population that is 100% mutator. These experiments are discussed in
      relation to ideas that an early step in carcinogenesis is the creation of a
      mutator phenotype.

PMID- 8990292
TI  - Cloning, analysis, and overexpression of the gene encoding isobutylamine N
      hydroxylase from the valanimycin producer, Streptomyces viridifaciens.
AB  - The flavoprotein isobutylamine N-hydroxylase (IBAH) catalyzes the oxidation of
      isobutylamine to isobutylhydroxylamine, a key step in the biosynthesis of the
      azoxy antibiotic valanimycin. By using oligonucleotide primers designed from
      peptide sequence information derived from native IBAH, a fragment of the gene
      (vlmH) encoding IBAH was amplified by PCR from a genomic library of the
      valanimycin-producing organism, Streptomyces viridifaciens MG456-hF10. The gene
      fragment was then employed as a probe to clone the entire vlmH gene from an S.
      viridifaciens genomic library. Overexpression of the vlmH gene in Escherichia
      coli gave a soluble protein that was purified to homogeneity. The purified
      protein exhibited the catalytic activity expected for IBAH. The deduced amino
      acid sequence of IBAH exhibited the greatest similarity to the Sox/DszC protein
      from Rhodococcus sp. strain IGT38, a flavoprotein involved in the oxidation of
      dibenzothiophene to the corresponding sulfone. Significant similarities were also
      found between the amino acid sequence of IBAH and those of the acyl coenzyme A
      dehydrogenases.

PMID- 8990294
TI  - The -45 region of the Escherichia coli lac promoter: CAP-dependent and CAP
      independent transcription.
AB  - The lactose (lac) operon promoter is positively regulated by the catabolite gene
      activator-cyclic AMP complex (CAP) that binds to the DNA located 61.5 bp upstream
      of the transcription start site. Between the CAP binding site and the core
      promoter sequence is a 13-bp sequence (from -38 to -50 [the -45 region]). The
      possible roles of the -45 region in determining the CAP-independent level of lac
      expression and in the CAP activation process were studied by isolating and
      characterizing random multisite mutations. Only a small percentage of mutants
      have dramatic effects on lac promoter activity. Among the mutations that did
      affect expression, a 26-fold range in lac promoter activity in vivo was observed
      in the CAP-independent activity. The highest level of CAP-independent lac
      expression (13-fold the level of the wild-type lac promoter) correlated with
      changes in the -40 to -45 sequence and required an intact RNA polymerase alpha
      subunit for in vitro expression, as expected for an upstream DNA recognition
      element. Mutant promoters varied in their ability to be stimulated by CAP in
      vivo, with levels ranging from 2-fold to the wild-type level of 22-fold. Only a
      change of twofold in responsiveness to CAP could be attributed to direct DNA
      sequence effects. The -40 to -45 sequence-dependent enhancement of promoter
      activity and CAP stimulation of promoter activity did not act additively. The
      mutant promoters also displayed other characteristics, such as the activation of
      nascent promoter-like activities overlapping lac P1 and, in one case, replicon
      dependent changes in promoter activity.

PMID- 8990295
TI  - A novel member of the subtilisin-like protease family from Streptomyces
      albogriseolus.
AB  - We previously isolated three extracellular endogenous enzymes from a Streptomyces
      albogriseolus mutant strain which were targets of Streptomyces subtilisin
      inhibitor (SSI) (S. Taguchi, A. Odaka, Y. Watanabe, and H. Momose, Appl. Environ.
      Microbiol. 61:180-186, 1995). In the present study, of the three enzymes the
      largest one, with a molecular mass of 45 kDa (estimated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis), termed SAM-P45, has been characterized in
      detail. The entire gene encoding SAM-P45 was cloned as an approximately 10-kb
      fragment from S. albogriseolus S-3253 genomic DNA into an Escherichia coli host
      by using a shuttle plasmid vector. The amino acid sequence corresponding to the
      internal region of SAM-P45, deduced from the nucleotide sequence of the gene,
      revealed high homology, particularly in three regions around the active-site
      residues (Asp, His, and Ser), with the amino acid sequences of the mature domain
      of subtilisin-like serine proteases. In order to investigate the enzymatic
      properties of this protease, recombinant SAM-P45 was overproduced in Streptomyces
      coelicolor by using a strong SSI gene promoter. Sequence analysis of the SAM-P45
      gene and peptide mapping of the purified SAM-P45 suggested that it is synthesized
      as a large precursor protein containing a large C-terminal prodomain (494
      residues) in addition to an N-terminal preprodomain (23 and 172 residues). A high
      proportion of basic amino acids in the C-terminal prodomain was considered to
      serve an element interactive with the phospholipid bilayer existing in the C
      terminal prodomain, as found in other membrane-anchoring proteases of gram
      positive bacteria. It is noteworthy that SAM-P45 was found to prefer basic amino
      acids to aromatic or aliphatic amino acids in contrast to subtilisin BPN', which
      has a broad substrate specificity. The hydrolysis by SAM-P45 of the synthetic
      substrate (N-succinyl-L-Gly-L-Pro-L-Lys-p-nitroanilide) most preferred by this
      enzyme was inhibited by SSI, chymostatin, and EDTA. The proteolytic activity of
      SAM-P45 was stimulated by the divalent cations Ca2+ and Mg2+. From these
      findings, we conclude that SAM-P45 interacts with SSI and can be categorized as a
      novel member of the subtilisin-like serine protease family.

PMID- 8990296
TI  - pigB determines a diffusible factor needed for extracellular polysaccharide slime
      and xanthomonadin production in Xanthomonas campestris pv. campestris.
AB  - Seven xanthomonadin transcriptional units (pigA through pigG) were identified by
      transposon saturation mutagenesis within an 18.6-kbp portion of the previously
      identified 25.4-kbp pig region from Xanthomonas campestris pv. campestris (strain
      B-24). Since marker exchange mutant strains with insertions in one 3.7-kbp
      portion of pig could not be obtained, mutations in this region may be lethal to
      the bacterium. Complementation analyses with different insertion mutations
      further defined and confirmed the seven transcriptional units. Insertional
      inactivation of one of the transcriptional units, pigB, resulted in greatly
      reduced levels of both xanthomonadins and extracellular polysaccharide slime, and
      a pigB-encoding plasmid restored both traits to these strains. pigB mutant
      strains could also be restored extracellularly by growth adjacent to strains with
      insertion mutations in any of the other six xanthomonadin transcriptional units,
      the parent strain (B-24), or strains of five different species of Xanthomonas.
      Strain B-24 produced a nontransforming diffusible factor (DF), which could be
      restored to pigB mutants by the pigB-encoding plasmid. Several lines of evidence
      indicate that DF is a novel bacterial pheromone, different from the known signal
      molecules of Vibrio, Agrobacterium, Erwinia, Pseudomonas, and Burkholderia spp.

PMID- 8990297
TI  - Heat shock regulation of sigmaS turnover: a role for DnaK and relationship
      between stress responses mediated by sigmaS and sigma32 in Escherichia coli.
AB  - The cellular level of the rpoS-encoded sigmaS subunit of RNA polymerase increases
      in response to various stress situations that include starvation, high
      osmolarity, and shift to acid pH, and these different stress signals
      differentially affect rpoS translation and/or sigmaS stability. Here we
      demonstrate that sigmaS is also induced by heat shock and that this induction is
      exclusively due to an interference with sigmaS turnover. Some sigmaS-dependent
      genes exhibit similar heat shock induction, whereas others are not induced
      probably because they need additional regulatory factors that might not be
      present under conditions of heat shock or exponential growth. Despite its
      induction, sigmaS does not seem to contribute to heat adaptation but may induce
      cross-protection against different stresses. While sigmaS is not involved in the
      regulation of the heat shock sigma factor sigma32, the heat shock protein DnaK
      has a positive role in the posttranscriptional control of sigmaS. The present
      evidence suggests that DnaK is involved in the transduction of two of the signals
      that result in reduced sigmaS turnover, i.e., heat shock and carbon starvation.
      Heat shock induction of sigmaS also clearly indicates that a cessation of growth
      or even a reduction of the growth rate is not a prerequisite for the induction of
      sigmaS and sigmaS-dependent genes and underscores the importance of sigmaS as a
      general stress sigma factor.

PMID- 8990298
TI  - The VirB4 ATPase of Agrobacterium tumefaciens is a cytoplasmic membrane protein
      exposed at the periplasmic surface.
AB  - The VirB4 ATPase of Agrobacterium tumefaciens, a putative component of the T
      complex transport apparatus, associates with the cytoplasmic membrane
      independently of other products of the Ti plasmid. VirB4 was resistant to
      extraction from membranes of wild-type strain A348 or a Ti-plasmidless strain
      expressing virB4 from an IncP replicon. To evaluate the membrane topology of
      VirB4, a nested deletion method was used to generate a high frequency of random
      fusions between virB4 and 'phoA, which encodes a periplasmically active alkaline
      phosphatase (AP) deleted of its signal sequence. VirB4::PhoA hybrid proteins
      exhibiting AP activity in Escherichia coli and A. tumefaciens had junction sites
      that mapped to two regions, between residues 58 and 84 (region 1) and between
      residues 450 and 514 (region 2). Conversely, VirB4::beta-galactosidase hybrid
      proteins with junction sites mapping to regions 1 and 2 exhibited low beta
      galactosidase activities and hybrid proteins with junction sites elsewhere
      exhibited high beta-galactosidase activities. Enzymatically active VirB5::PhoA
      hybrid proteins had junction sites that were distributed throughout the length of
      the protein. Proteinase K treatment of A. tumefaciens spheroplasts resulted in
      the disappearance of the 87-kDa VirB4 protein and the concomitant appearance of
      two immunoreactive species of approximately 35 and approximately 45 kDa. Taken
      together, our data support a model in which VirB4 is topologically configured as
      an integral cytoplasmic membrane protein with two periplasmic domains.

PMID- 8990299
TI  - Increase in chitin as an essential response to defects in assembly of cell wall
      polymers in the ggp1delta mutant of Saccharomyces cerevisiae.
AB  - The GGP1/GAS1 gene codes for a glycosylphosphatidylinositol-anchored plasma
      membrane glycoprotein of Saccharomyces cerevisiae. The ggp1delta mutant shows
      morphogenetic defects which suggest changes in the cell wall matrix. In this
      work, we have investigated cell wall glucan levels and the increase of chitin in
      ggp1delta mutant cells. In these cells, the level of alkali-insoluble 1,6-beta-D
      glucan was found to be 50% of that of wild-type cells and was responsible for the
      observed decrease in the total alkali-insoluble glucan. Moreover, the ratio of
      alkali-soluble to alkali-insoluble glucan almost doubled, suggesting a change in
      glucan solubility. The increase of chitin in ggp1delta cells was found to be
      essential since the chs3delta ggp1delta mutations determined a severe reduction
      in the growth rate and in cell viability. Electron microscopy analysis showed the
      loss of the typical structure of yeast cell walls. Furthermore, in the chs3delta
      ggp1delta cells, the level of alkali-insoluble glucan was 57% of that of wild
      type cells and the alkali-soluble/alkali-insoluble glucan ratio was doubled. We
      tested the effect of inhibition of chitin synthesis also by a different approach.
      The ggp1delta cells were treated with nikkomycin Z, a well-known inhibitor of
      chitin synthesis, and showed a hypersensitivity to this drug. In addition,
      studies of genetic interactions with genes related to the construction of the
      cell wall indicate a synthetic lethal effect of the ggp1delta kre6delta and the
      ggp1delta pkc1delta combined mutations. Our data point to an involvement of the
      GGP1 gene product in the cross-links between cell wall glucans (1,3-beta-D
      glucans with 1,6-beta-D-glucans and with chitin). Chitin is essential to
      compensate for the defects due to the lack of Ggp1p. Moreover, the activities of
      Ggp1p and Chs3p are essential to the formation of the organized structure of the
      cell wall in vegetative cells.

PMID- 8990301
TI  - Nitrate assimilation gene cluster from the heterocyst-forming cyanobacterium
      Anabaena sp. strain PCC 7120.
AB  - A region of the genome of the filamentous, nitrogen-fixing, heterocyst-forming
      cyanobacterium Anabaena sp. strain PCC 7120 that contains a cluster of genes
      involved in nitrate assimilation has been identified. The genes nir, encoding
      nitrite reductase, and nrtABC, encoding elements of a nitrate permease, have been
      cloned. Insertion of a gene cassette into the nir-nrtA region impaired expression
      of narB, the nitrate reductase structural gene which together with nrtD is found
      downstream from nrtC in the gene cluster. This indicates that the nir-nrtABCD
      narB genes are cotranscribed, thus constituting an operon. Expression of the nir
      operon in strain PCC 7120 is subjected to ammonium-promoted repression and takes
      place from an NtcA-activated promoter located 460 bp upstream from the start of
      the nir gene. In the absence of ammonium, cellular levels of the products of the
      nir operon are higher in the presence of nitrate than in the absence of combined
      nitrogen.

PMID- 8990300
TI  - Cloning and heterologous expression of the entire gene clusters for PD 116740
      from Streptomyces strain WP 4669 and tetrangulol and tetrangomycin from
      Streptomyces rimosus NRRL 3016.
AB  - The genes for the complete pathways for two polycyclic aromatic polyketides of
      the angucyclinone class have been cloned and heterologously expressed. Genomic
      DNAs of Streptomyces rimosus NRRL 3016 and Streptomyces strain WP 4669 were
      partially digested with MboI, and libraries (ca. 40-kb fragments) in Escherichia
      coli XL1-Blue MR were prepared with the cosmid vector pOJ446. Hybridization with
      the actI probe from the actinorhodin polyketide synthase genes identified two
      clusters of polyketide genes from each organism. After transfer of the four
      clusters to Streptomyces lividans TK24, expression of one cluster from each
      organism was established through the identification of pathway-specific products
      by high-performance liquid chromatography with photodiode array detection. Peaks
      were identified from the S. rimosus cluster (pksRIM-1) for tetrangulol,
      tetrangomycin, and fridamycin E. Peaks were identified from the WP 4669 cluster
      (pksWP-2) for tetrangulol, 19-hydroxytetrangulol, 8-O-methyltetrangulol, 19
      hydroxy-8-O-methyltetrangulol, and PD 116740. Structures were confirmed by 1H
      nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

PMID- 8990302
TI  - Cloning and characterization of two groESL operons of Rhodobacter sphaeroides:
      transcriptional regulation of the heat-induced groESL operon.
AB  - The nonsulfur purple bacterium Rhodobacter sphaeroides was found to contain two
      groESL operons. The groESL1 heat shock operon was cloned from a genomic library,
      and a 2.8-kb DNA fragment was sequenced and found to contain the groES and groEL
      genes. The deduced amino acid sequences of GroEL1 (cpn60) and GroES1 (cpn10) were
      in agreement with N-terminal sequences previously obtained for the isolated
      proteins (K. C. Terlesky and F. R. Tabita, Biochemistry 30:8181-8186, 1991).
      These sequences show a high degree of similarity to groESL genes isolated from
      other bacteria. Northern analysis indicated that the groESL1 genes were expressed
      as part of a 2.2-kb polycistronic transcript that is induced 13-fold after heat
      shock. Transcript size was not affected by heat shock; however, the amount of
      transcript was induced to its greatest extent 15 to 30 min after a 40 degrees C
      heat shock, from an initial temperature of 28 degrees C, and remained elevated up
      to 120 min. The R. sphaeroides groESL1 operon contains a putative hairpin loop at
      the start of the transcript that is present in other bacterial heat shock genes.
      Primer extension of the message showed that the transcription start site is at
      the start of this conserved hairpin loop. In this region were also found putative
      -35 and -10 sequences that are conserved upstream from other bacterial heat shock
      genes. Transcription of the groESL1 genes was unexpectedly low under
      photoautotrophic growth conditions. Thus far, it has not been possible to
      construct a groESL1 deletion strain, perhaps indicating that these genes are
      essential for growth. A second operon (groESL2) was also cloned from R.
      sphaeroides, using a groEL1 gene fragment as a probe; however, no transcript was
      observed for this operon under several different growth conditions. A groESL2
      deletion strain was constructed, but there was no detectable change in the
      phenotype of this strain compared to the parental strain.

PMID- 8990304
TI  - Characterization of dapB, a gene required by Pseudomonas syringae pv. tabaci
      BR2.024 for lysine and tabtoxinine-beta-lactam biosynthesis.
AB  - The dapB gene, which encodes L-2,3-dihydrodipicolinate reductase, the second
      enzyme of the lysine branch of the aspartic amino acid family, was cloned and
      sequenced from a tabtoxin-producing bacterium, Pseudomonas syringae pv. tabaci
      BR2.024. The deduced amino acid sequence shared 60 to 90% identity to known dapB
      gene products from gram-negative bacteria and 19 to 21% identity to the dapB
      products from gram-positive bacteria. The consensus sequence for the NAD(P)H
      binding site [(V/I)(A/G)(V/I)XGXXGXXG)] and the proposed substrate binding site
      (HHRHK) were conserved in the polypeptide. A BR2.024 dapB mutant is a
      diaminopimelate auxotroph and tabtoxin negative. The addition of a mixture of L
      ,L-, D,D-, and meso-diaminopimelate to defined media restored growth but not
      tabtoxin production. Cloned DNA fragments containing the parental dapB gene
      restored the ability to grow in defined media and tabtoxin production to the dapB
      mutant. These results indicate that the dapB gene is required for both lysine and
      tabtoxin biosynthesis, thus providing the first genetic evidence that the
      biosynthesis of tabtoxin proceeds in part along the lysine biosynthetic pathway.
      These data also suggest that L-2,3,4,5-tetrahydrodipicolinate is a common
      intermediate for both lysine and tabtoxin biosynthesis.

PMID- 8990305
TI  - The Caulobacter heat shock sigma factor gene rpoH is positively autoregulated
      from a sigma32-dependent promoter.
AB  - Sigma factor sigma32, encoded by rpoH, is required for the recognition of heat
      shock genes during normal growth conditions and in response to heat shock and
      other stresses. Unlike the well-studied Escherichia coli rpoH gene, which is
      transcribed from four promoters recognized by either a sigma70 (sigmaD)- or
      sigma24 (sigmaE)-containing RNA polymerase, the Caulobacter crescentus rpoH gene
      is transcribed from two promoters, P1 and P2. In this study, we have examined the
      structure and expression of these promoters and shown that the rpoH P2 promoter
      is sigma32 dependent. We present evidence here that P2 is specifically recognized
      and transcribed by the reconstituted C. crescentus Esigma32 RNA polymerase
      holoenzyme. We show that site-directed mutations within either the -10 or the -35
      regions of P2 have substantial effects on the levels of transcription by the
      Esigma32 polymerase predicted from the sigma32 promoter consensus sequence. The
      mutations have similar effects in vivo as assayed with rpoH-lacZ transcription
      fusions. Analysis of the rpoH P1 promoter provided evidence that it is sigma70
      dependent. S1 nuclease protection assays of rpoH P1- and P2-specific expression
      after heat shock at 42 or 50 degrees C and during synchronous cell division
      cycles under normal growth conditions showed that the two promoters are
      differentially regulated. Mutations within the rpoH P2 promoter consensus
      sequences abolished the response to heat shock induction in C. crescentus. We
      conclude from these results that, unlike rpoH genes studied previously in other
      bacteria, the major transcriptional response of the C. crescentus rpoH gene to
      heat shock depends on positive autoregulation of the sigma32-dependent promoter.

PMID- 8990303
TI  - Identification and characterization of a new beta-glucoside utilization system in
      Bacillus subtilis.
AB  - A new catabolic system in Bacillus subtilis involved in utilization of beta
      glucosidic compounds has been investigated. It consists of five genes encoding
      phosphotransferase system (PTS) enzyme II (licB and licC) and enzyme IIA (licA),
      a presumed 6-phospho-beta-glucosidase (licH), as well as a putative regulator
      protein (licR). The genes map around 334 degrees of the B. subtilis chromosome,
      and their products are involved in the uptake and utilization of lichenan
      degradation products. These five genes are organized in two transcriptional
      units. A weak promoter precedes gene licR, and transcription is obviously
      terminated at a secondary structure immediately downstream of the reading frame,
      as shown by Northern RNA blot analysis. Genes licB, licC, licA, and licH
      constitute an operon. Initiation of transcription at the promoter in front of
      this operon presumably requires activation by the gene product of licR. The LicR
      protein shows an unusual domain structure, i.e., similarities to (i) the
      conserved transcriptional antiterminator BgIG family signature and (ii) PTS
      enzyme II. Using RNA techniques and transcriptional lacZ fusions, we have shown
      that the expression of the licBCAH operon is inducible by products of lichenan
      hydrolysis, lichenan and cellobiose. The presence of excess glucose prevents the
      induction of this operon, indicating the control by carbon catabolite repression.
      Moreover, the expression of the operon requires the general PTS components and
      seems to be negatively controlled by the specific lic PTS enzymes.

PMID- 8990306
TI  - Expression of AbrB, a transition state regulator from Bacillus subtilis, is
      growth phase dependent in a manner resembling that of Fis, the nucleoid binding
      protein from Escherichia coli.
AB  - The transition state regulator AbrB functions as an activator, a repressor, and a
      preventer of gene expression in Bacillus subtilis. In this paper, we show that
      expression of abrB is growth phase dependent. Accumulation of abrB transcript is
      restricted to a short period spanning the transition between the lag and
      exponential phases of the growth cycle. The level of abrB transcript then falls
      sharply, and transcript cannot be detected at the mid-exponential period of the
      growth cycle. The level of AbrB protein is also maximal during early exponential
      growth but decreases gradually throughout the remainder of the growth cycle. The
      abrupt reduction of abrB transcript level during the early period of the growth
      cycle is effected by the phosphorylated form of the response regulator Spo0p3and
      to a lesser extent by negative autoregulation. The growth cycle-dependent
      expression of abrB is very similar to that observed for fis in Escherichia coli
      and in Salmonella typhimurium. Although AbrB and Fis are not homologous proteins,
      they display extensive similarity in terms of size, DNA binding characteristics,
      growth cycle-dependent patterns of expression, and their control over the
      expression of a varied group of operons. We hypothesize therefore that AbrB, like
      Fis, is a nucleoid binding protein.

PMID- 8990308
TI  - Maintenance of broad-host-range incompatibility group P and group Q plasmids and
      transposition of Tn5 in Bartonella henselae following conjugal plasmid transfer
      from Escherichia coli.
AB  - The first demonstration of conjugal plasmid transfer from Escherichia coli to
      Bartonella henselae is reported. Transconjugants bearing plasmids of
      incompatibility groups P (IncP) and Q (IncQ), expressing various resistance
      markers, were generated. Tn5 transposons delivered on suicide plasmids by
      conjugation showed transpositional insertion into random chromosomal sites.

PMID- 8990307
TI  - Function of the C-terminal domain of the alpha subunit of Escherichia coli RNA
      polymerase in basal expression and integration host factor-mediated activation of
      the early promoter of bacteriophage Mu.
AB  - Integration host factor (IHF) can activate transcription from the early promoter
      (Pe) of bacteriophage Mu both directly and indirectly. Indirect activation occurs
      through alleviation of H-NS-mediated repression of the Pe promoter (P. Van Ulsen,
      M. Hillebrand, L. Zulianello, P. Van de Putte, and N. Goosen, Mol. Microbiol.
      21:567-578, 1996). The direct activation involves the C-terminal domain of the
      alpha subunit (alphaCTD) of RNA polymerase. We investigated which residues in the
      alphaCTD are important for IHF-mediated activation of the Pe promoter. Initial in
      vivo screening, using a set of substitution mutants derived from an alanine scan
      (T. Gaal, W. Ross, E. E. Blatter, T. Tang, X. Jia, V. V. Krishnan, N. Assa-Munt,
      R. Ebright, and R. L. Gourse, Genes Dev. 10:16-26, 1996; H. Tang, K. Severinov,
      A. Goldfarb, D. Fenyo, B. Chait, and R. H. Ebright, Genes Dev. 8:3058-3067,
      1994), indicated that the residues, which are required for transcription
      activation by the UP element of the rrnB P1 promoter (T. Gaal, W. Ross, E. E.
      Blatter, T. Tang, X. Jia, V. V. Krishnan, N. Assa-Munt, R. Ebright, and R. L.
      Gourse, Genes Dev. 10:16-26, 1996), are also important for Pe expression in the
      presence of IHF. Two of the RNA polymerase mutants, alphaR265A and alphaG296A,
      that affected Pe expression most in vivo were subsequently tested in in vitro
      transcription experiments. Mutant RNA polymerase with alphaR265A showed no IHF
      mediated activation and a severely reduced basal level of transcription from the
      Pe promoter. Mutant RNA polymerase with alphaG296A resulted in a slightly reduced
      transcription from the Pe promoter in the absence of IHF but could still be
      activated by IHF. These results indicate that interaction of the alphaCTD with
      DNA is involved not only in the IHF-mediated activation of Pe transcription but
      also in maintaining the basal level of transcription from this promoter.
      Mutational analysis of the upstream region of the Pe promoter identified a
      sequence, positioned from -39 to -51 with respect to the transcription start
      site, that is important for basal Pe expression, presumably through binding of
      the alphaCTD. The role of the alphaCTD in IHF-mediated stimulation of
      transcription from the Pe promoter is discussed.

PMID- 8990310
TI  - Isolation and characterization of a sporulation initiation mutation in the
      Bacillus subtilis secA gene.
AB  - A Bacillus subtilis secA mutant, secA12, which is blocked at an early stage of
      sporulation, is able to grow as well as the wild-type strain at all temperatures
      tested. Experiments with lacZ fusion genes showed that the induction of kinA
      expression, as well as the sporulation-specific transcription of the spo0A gene,
      was not observed in the secA12 mutant. However, transcription of the spo0H gene
      (coding for sigmaH, which is required for the transcription of kinA and spo0A)
      and accumulation of the sigmaH protein were not affected in secA12. These results
      suggested that mutations in secA affect a factor required for efficient
      transcription of kinA as well as for the activation of the phosphorelay pathway.

PMID- 8990311
TI  - Isolation, sequence, and expression of the gene encoding halocin H4, a
      bacteriocin from the halophilic archaeon Haloferax mediterranei R4.
AB  - The first gene to encode a haloarchaeal bacteriocin (halocin H4) has been cloned
      and sequenced from Haloferax mediterranei R4. Both the signal sequence in the
      halocin H4 preprotein and the monocistronic halH4 gene have some unusual
      features. The physiology of halH4 expression reveals that although halH4
      transcripts are present at low basal levels during exponential growth, halocin H4
      activity first appears as the culture enters stationary phase. As halocin
      activity levels increase, so do transcript levels, but then activity levels
      decrease precipitously while transcript levels remain elevated.

PMID- 8990309
TI  - Nitrogenase phylogeny and the molybdenum dependence of nitrogen fixation in
      Methanococcus maripaludis.
AB  - We studied the effects of molybdenum, vanadium, and tungsten on the diazotrophic
      growth of Methanococcus maripaludis. Mo stimulated growth, with a maximal
      response at 4.0 microM, while V had no effect at any concentration tested. W
      specifically inhibited diazotrophic growth in the presence of Mo. Coupling the
      results of our analysis and other known metal requirements with phylogenies
      derived from nifD and nifK genes revealed distinct clusters for Mo-, V-, and Fe
      dinitrogenases and suggested that most methanogens also have molybdenum-type
      nitrogenases.

PMID- 8990313
TI  - Quorum sensing in Vibrio fischeri: essential elements for activation of the
      luminescence genes.
AB  - LuxR is required for cell density-dependent activation of the Vibrio fischeri
      luminescence (lux) genes. It has not been possible to study full-length LuxR in
      vitro, but a polypeptide containing the C-terminal transcriptional-activator
      domain of LuxR (LuxRdeltaN) has been purified, and its binding to lux regulatory
      DNA has been investigated. By itself, LuxRdeltaN interacts with a region of lux
      regulatory DNA that is upstream of the lux box, which is a 20-bp element that is
      required for LuxR activation of the luminescence operon. Individually, neither
      the purified LuxRdeltaN nor RNA polymerase binds to the lux box region, but
      together the two proteins bind in synergy to the lux box-luxI promoter region. We
      show that binding of LuxRdeltaN to the upstream region is not a prerequisite for
      its synergistic binding with RNA polymerase to the lux box and the luxI promoter
      region. We also show that LuxRdeltaN and RNA polymerase are both required and
      sufficient for transcriptional activation of the lux operon. This argues against
      the hypothesis that LuxR functions to alleviate repression of the lux operon by
      another cellular factor. Rather, our data support the view that LuxR functions as
      an accessory factor that enables RNA polymerase to bind to and initiate
      transcription from the promoter of the lux operon.

PMID- 8990312
TI  - An unexpected flaA homolog is present and expressed in Borrelia burgdorferi.
AB  - Most investigators have assumed that the periplasmic flagella (PFs) of Borrelia
      burgdorferi are composed of only one flagellin protein. The PFs of most other
      spirochete species are complex: these PFs contain an outer sheath of FlaA
      proteins and a core filament of FlaB proteins. During an analysis of a chemotaxis
      gene cluster of B. burgdorferi 212, we were surprised to find a flaA gene homolog
      with a deduced polypeptide having 54 to 58% similarity to FlaA from other
      spirochetes. Like other FlaA proteins, B. burgdorferi FlaA has a conserved signal
      sequence at its N terminus. Based on reverse transcription-PCR and primer
      extension analysis, this flaA homolog and five chemotaxis genes constitute a
      motility-chemotaxis operon. Immunoblots using anti-FlaA serum from Treponema
      pallidum and a lysate of B. burgdorferi showed strong reactivity to a protein of
      38.0 kDa, which is consistent with the expression of flaA in growing cells.

PMID- 8990314
TI  - Occurrence and biosynthesis of 5-aminoimidazole-4-carboxamide ribonucleotide and
      N-(beta-D-ribofuranosyl)formamide 5'-phosphate in Methanobacterium
      thermoautotrophicum delta(H).
AB  - 5-Aminoimidazole-4-carboxamide ribonucleotide (ZMP) and N-(beta-D
      ribofuranosyl)formamide 5'-phosphate (FAR-P) have been identified as products of
      the metabolism of ATP and 5-phospho-alpha-D-ribosyl diphosphate by
      Methanobacterium thermoautotrophicum delta(H), a member of the domain Archaea.
      Evidence indicates that the first three steps in the pathway to the formation of
      these compounds are the same as the first three steps of histidine biosynthesis
      and lead to the generation of pro-phosphoribosyl formimino-5-aminoimidazole-4
      carboxamide ribonucleotide (5'-proFAR). The 5'-proFAR then undergoes hydrolysis
      to ZMP and FAR-P. The reaction was detected by an unexpected high concentration
      of ZMP in cell extracts of M. thermoautotrophicum delta(H).

PMID- 8990315
TI  - Public health experts take aim at a moving target: foodborne infections.

PMID- 8990317
TI  - NHANES III health data relevant for aging nation.

PMID- 8990316
TI  - Rheumatologists issue guidelines for preventing and treating corticosteroid
      induced osteoporosis.

PMID- 8990318
TI  - From the Centers for Disease Control and Prevention. Coccidioidomycosis--Arizona,
      1990-1995.

PMID- 8990319
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States, 1996-97 season.

PMID- 8990320
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990321
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990322
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990323
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990324
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990325
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990326
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990327
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990328
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990329
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990330
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990331
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990332
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990333
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990334
TI  - Effectiveness of right heart catheterization: time for a randomized trial.

PMID- 8990335
TI  - Adverse outcomes of underuse of beta-blockers in elderly survivors of acute
      myocardial infarction.
AB  - OBJECTIVES: To study determinants and adverse outcomes (mortality and
      rehospitalization) of beta-blocker underuse in elderly patients with myocardial
      infarction; and whether the relative risks (RRs) of survival associated with beta
      blocker use were comparable to those reported in the large randomized controlled
      trials (RCTs). SETTING: New Jersey Medicare population. DESIGN: Retrospective
      cohort design using linked Medicare and drug claims data from 1987 to 1992.
      PATIENTS: Statewide cohort of 5332 elderly 30-day acute myocardial infarction
      (AMI) survivors with prescription drug coverage, of whom 3737 were eligible for
      beta-blockers. MAIN OUTCOME MEASURES: beta-Blocker and calcium channel blocker
      use in the first 90 days after discharge and mortality rates and cardiac hospital
      readmissions over the 2-year period after discharge, controlling for
      sociodemographic and baseline risk variables. RESULTS: Only 21% of eligible
      patients received beta-blocker therapy; this rate remained unchanged from 1987 to
      1991. Patients were almost 3 times more likely to receive a new prescription for
      a calcium channel blocker than for a new beta-blocker after their AMIs. Advanced
      age and calcium channel blocker use predicted underuse of beta-blockers.
      Controlling for other predictors of survival, the mortality rate among beta
      blocker recipients was 43% less than that for nonrecipients (RR=0.57; 95%
      confidence interval [CI], 0.47-0.69). Effects on mortality were substantial in
      all age strata (65-74 years, 75-84 years, and > or = 85 years) and consistent
      with the results for elderly subgroups of 2 large RCTs. beta-Blocker recipients
      were rehospitalized 22% less often than nonrecipients (RR=0.78; 95% CI, 0.67
      0.90). Use of a calcium channel blocker instead of a beta-blocker was associated
      with a doubled risk of death (RR= 1.98; 95% CI, 1.44-2.72), not because calcium
      channel blockers had a demonstrable adverse effect, but because they were
      substitutes for beta-blockers. CONCLUSIONS: beta-Blockers are underused in
      elderly AMI survivors, leading to measurable adverse outcomes. These data suggest
      that the survival benefits of beta-blockade after an AMI may extend to eligible
      patients older than 75 years, a group that has been excluded from RCTs.

PMID- 8990336
TI  - Prevalence of alcohol-impaired driving. Results from a national self-reported
      survey of health behaviors.
AB  - OBJECTIVE: To estimate how frequently adults in the United States drive while
      impaired by alcohol. DESIGN: Telephone survey. SETTING: The 49 states (and the
      District of Columbia) that participated in the Behavioral Risk Factor
      Surveillance System (BRFSS) in 1993. PARTICIPANTS: A total of 102,263
      noninstitutionalized adults aged 18 years or older. MAIN OUTCOME MEASURES: The
      percentage of respondents who reported alcohol-impaired driving; number of
      episodes of alcohol-impaired driving per 1000 adult population; and total number
      of episodes of alcohol-impaired driving-each by age, sex, race, level of
      education, and state. RESULTS: Overall, 2.5% of adults reported an estimated 123
      million episodes of alcohol-impaired driving in 1993. This corresponds to 655
      episodes of alcohol-impaired driving for each 1000 adults (range among states per
      1000 adults, 165-1550). Alcohol-impaired driving was most frequent among men aged
      21 to 34 years (1739 episodes per 1000 adults) and was nearly as frequent among
      men aged 18 to 20 years (1623 episodes per 1000 adults), despite legislation in
      all states that prohibited the sale of alcohol to persons younger than age 21
      years in 1993. CONCLUSIONS: Alcohol-impaired driving is common even among
      underage persons. Strict enforcement of laws that discourage alcohol-impaired
      driving is needed along with community and patient education to reduce the
      prevalence of alcohol-impaired driving and prevent injuries and deaths from
      alcohol-related motor vehicle crashes. Data from the BRFSS, an ongoing source of
      national and state-specific data on the number of episodes of alcohol-impaired
      driving, are potentially useful for monitoring trends and evaluating the effect
      of future efforts to reduce alcohol-impaired driving.

PMID- 8990337
TI  - Results at age 8 years of early intervention for low-birth-weight premature
      infants. The Infant Health and Development Program.
AB  - OBJECTIVE: To reevaluate at age 8 years children who had participated during the
      first 3 years of life in a randomized clinical trial of special services for low
      birthweight (LBW) premature infants. DESIGN: Follow-up of a randomized controlled
      trial of premature infants (< or = 37 weeks' gestation), stratified by 2 LBW
      groups (lighter [< or = 2000 g] and heavier [2001-2500 g]) and divided into
      intervention (n=377) and follow-up only (n=608) groups. SETTING: Eight sites
      serving diverse populations. PARTICIPANTS: At age 8 years, 874 children were
      assessed: 336 in the intervention group and 538 in the follow-up only group.
      INTERVENTION: The 3-year intervention consisted of home visits (birth to 3
      years), child development center services (ages 1 to 3 years), and parent group
      meetings (ages 1 to 3 years). PRIMARY OUTCOME MEASURES: Cognitive functioning
      (Weschler Intelligence Scale for Children-III; Peabody Picture Vocabulary Test
      Revised); academic achievement (Woodcock-Johnson Tests of Achievement-Revised);
      and parental reports of school performance, behavior (Child Behavior Checklist),
      and health (Child General Health Survey). RESULTS: At age 8 years, in the entire
      cohort and in the lighter LBW stratum, the intervention and follow-up only groups
      were similar on all primary outcome measures. Differences favoring the
      intervention group were found within the heavier LBW group: full-scale IQ score
      (4.4 points higher, P=.007), verbal IQ score (4.2 points higher, P=.01),
      performance IQ score (3.9 points higher, P=.02), mathematics achievement score
      (4.8 points higher, P=.04), and receptive vocabulary score (6.7 points higher,
      P=.001). On a physical functioning subscale, the whole intervention group
      received less favorable ratings, while the lighter LBW intervention group had
      lower maternal ratings assessing social limitations caused by behavior.
      CONCLUSION: Although at age 8 years there were modest intervention-related
      differences in the cognitive and academic skills of heavier LBW premature
      children, attenuation of the large favorable effects seen at 3 years was observed
      in both the heavier and lighter LBW groups. This indicates a need to develop
      additional intervention strategies for LBW premature children that can provide
      sustained benefits.

PMID- 8990338
TI  - Development of donor-derived prostate cancer in a recipient following orthotopic
      heart transplantation.
AB  - OBJECTIVE: To report the development of metastatic prostate cancer in a heart
      transplant recipient without a primary focus in the recipient prostate gland; to
      present genetic evidence suggesting transplantation of the malignancy from the
      donor. DESIGN: Histological analysis of donor prostate and recipient prostate and
      rib. Molecular genetic analysis of prostate and kidney tissue from the donor and
      peripheral blood leukocytes and rib tissue from the transplant recipient.
      SETTING: University of Pennsylvania Medical Center. RESULTS: Multiple biopsies of
      recipient prostate were negative for malignancy but recipient rib contained
      prostatic adenocarcinoma with osteoblastic bone response. Molecular genetic
      analysis of recipient rib specimen, which contained both histologically normal
      and neoplastic cells, was shown to contain a combination of alleles from the
      donor and recipient at 4 loci. CONCLUSION: Although this is a single case report
      of an uncommon event, genotyping of polymorphic dinucleotide repeat elements from
      4 different chromosomal regions provides strong evidence that the tumor cells
      arose from donor tissue and were transplanted along with the cardiac allograft.

PMID- 8990339
TI  - Charles Darwin and panic disorder.
AB  - Charles Darwin (1809-1882) suffered from a chronic illness that, throughout much
      of his adult life, impaired his functioning and severely limited his activities.
      The writings of this famous scientist as well as biographical materials indicate
      that he probably suffered from an anxiety disorder. His symptoms, when considered
      individually, suggest a variety of conditions, but taken together they point
      toward panic disorder with agoraphobia. This diagnosis brings coherence to
      Darwin's activities and explains his secluded lifestyle, including difficulty in
      speaking before groups and meeting with colleagues.

PMID- 8990340
TI  - Shatter resistance of spectacle lenses.
AB  - OBJECTIVE: To evaluate the relative strength and shatter resistance of spectacle
      lenses currently used in sunglasses and dress, sports, and industrial eyewear.
      DESIGN: Seven lenses that met the US American National Standards Institute (ANSI)
      Z80 standards for dress glasses (made of high-index plastic, allyl resin plastic,
      heat tempered glass, chemically tempered glass, and polycarbonate, and with
      center thickness ranging from 1 mm to 2.2 mm) and 4 lenses that met ANSI Z87
      standards for industrial safety eyewear (allyl resin plastic, heat-tempered
      glass, chemically tempered glass, and polycarbonate, all with 3.0-mm center
      thickness) were tested for impact resistance to 5 projectiles (air gun pellets,
      golf balls, tennis balls, lacrosse balls, and baseballs). MAIN OUTCOME MEASURES:
      Impact energy required to shatter spectacle lenses. RESULTS: Based on 348 lens
      impacts, dress and industrial lenses made from glass, allyl resin plastic, and
      high-index plastic shattered at impact energies less than those expected to be
      encountered from the test projectiles during their routine use. Polycarbonate
      lenses demonstrated resistance to impact for all tested projectiles exceeding the
      impact potential expected during routine use. CONCLUSIONS: Under the test
      conditions of this study, polycarbonate lenses demonstrated greater impact
      resistance than other commonly used spectacle lenses that conform to prevailing
      eyewear standards. These findings suggest that current ANSI Z80 and ANSI Z87
      standards should be reevaluated.

PMID- 8990341
TI  - HIV-1 protease inhibitors. A review for clinicians.
AB  - OBJECTIVE: The clinical care of people infected with human immunodeficiency virus
      (HIV) has been substantially affected by the introduction of HIV-specific
      protease inhibitors (PIs). The 4 PIs available are saquinavir mesylate,
      ritonavir, indinavir sulfate, and nelfinavir mesylate. Comparison studies have
      not been reported; therefore, an assessment of the available data to aid
      clinicians and patients in choosing appropriate treatment will be presented. DATA
      SOURCES: A systematic review of peer-reviewed publications, abstracts from
      national and international conferences, and product registration information
      through September 1996. STUDY SELECTION AND DATA EXTRACTION: Criteria used to
      select studies include their relevance to PIs, having been published in the
      English language, and pertinence for clinicians. Data quality and validity
      included the venue of the publication and relevance to clinical care. DATA
      SYNTHESIS: Oral adminstration of ritonavir, indinavir, or nelfinavir generates
      sustainable drug serum levels to effectively inhibit the protease enzyme;
      however, saquinavir may not generate sustained levels necessary to inhibit the
      protease enzyme. Patients treated with ritonavir, indinavir, or nelfinavir
      experience similar reductions in viral load and increases in CD4+ lymphocytes;
      smaller effects occur among those treated with saquinavir. Two randomized placebo
      controlled studies conducted among patients with severe immune system suppression
      and substantial zidovudine treatment experience demonstrated reduced HIV disease
      progression and reduced mortality with PI treatment. Genotypic resistance to PIs
      occurs; the clinical relevance of resistance is unclear. The costs of these
      agents including required monitoring impose new and substantial costs.
      CONCLUSIONS: The PIs have emerged as critical drugs for people with HIV
      infection. Optimal use involves combination with reverse transcriptase
      inhibitors. Resistance develops to each agent, and cross-resistance is likely.
      These agents must be used at full doses with attention to ensuring patient
      compliance. The expense of these agents may be offset by forestalling disease
      progression and death and returning people to productive life. Selecting the
      initial PI must be individualized, and factors to consider include proven
      activity, possible toxicities, dosing regimens, drug interactions, and costs.

PMID- 8990342
TI  - Tumors arising after organ transplantation. Sorting out their origins.

PMID- 8990343
TI  - Bridging the gap between research and practice. The role of continuing medical
      education.

PMID- 8990344
TI  - Five-year findings of the hypertension detection and follow-up program. I.
      Reduction in mortality of persons with high blood pressure, including mild
      hypertension. Hypertension Detection and Follow-up Program Cooperative Group.
      1979.

PMID- 8990346
TI  - Internet anatomy 101. Accessing information on the World Wide Web.

PMID- 8990345
TI  - The hypertension detection and follow-up program: 17 years on.

PMID- 8990347
TI  - Targeting of antihapten antibodies to activated T cells via an IL-2-hapten
      conjugate prolongs cardiac graft survival.
AB  - Antihapten antibodies binding to ligand-hapten conjugates are able to mediate
      complement mediated lysis in vitro. Based on this observation we propose a new in
      vivo immunotherapy using molecules that combine a low molecular weight hapten
      binding to antibodies preexisting in serum and a cell specific ligand. The ligand
      hapten conjugates are potential cytotoxic drugs which may (1) be specific for a
      given target cell, (2) be nonimmunogenic, (3) be of low molecular weight, (4)
      form soluble complexes with preexisting antibodies resulting in prolonged half
      life of the drug, and (5) induce a potent antibody mediated rejection of target
      cells. These novel compounds could be useful for the elimination of certain cell
      subsets involved in allograft rejection, cancers, infectious diseases, etc.,
      without some of the pitfalls of conventional immunotherapies. The feasibility of
      this approach was demonstrated in an animal model using a compound consisting of
      one interleukin 2 and one fluorescein molecule (IL-2-FITC). BALB/c mice (H2d)
      previously immunized and expressing anti-FITC antibodies were transplanted with a
      fully mismatched C57BL/6 (H2b) heterotopic heart allograft. Untreated controls
      rejected their graft by day 9 (MSD = 9 +/- 0.7). Mice with preexisting anti-FITC
      antibodies treated with IL-2-FITC maintained their grafts for 38.7 +/- 7.1 days
      (P < 0.02). No prolongation of graft survival was observed in immunized animals
      that were treated with IL-2 alone (MSD = 10 +/- 1.4). Nonimmunized animals
      treated with IL-2-FITC rejected their grafts on day 9.4 +/- 1.1. This
      demonstrates that IL-2-FITC therapy specifically prolonged graft survival in
      animals with circulating anti-FITC antibodies. The data suggest that a
      ligand/hapten pair can redirect preexisting antihapten antibodies toward target
      cells in vivo. Such compounds may be developed for human use as alternatives to
      polyclonal or monoclonal antibody therapy.

PMID- 8990348
TI  - Systemic administration of cellular interleukin-10 can exacerbate cardiac
      allograft rejection in mice.
AB  - Cellular interleukin-10 (cIL-10) has been shown to inhibit cytokine production by
      T helper type 1 (Th1) cells by blocking antigen presenting cell function. This
      activity has suggested that IL-10 might be useful in the treatment of transplant
      rejection. Stimulatory effects of IL-10 however, have also been observed both on
      T and B cell differentiation. In this study, we examined the influence of
      recombinant (r) mouse (m) IL-10 on heterotopic vascularized heart allograft
      survival in the B10(H2b)-->C3H(H2k) strain combination that crosses both major
      histocompatibility complex (MHC) and non-MHC-histocompatibility antigen (non-MHC
      HA) barriers. The influence of IL-10 was also examined in the B10.BR (H2k)--> C3H
      combination with disparity at only non-MHC-HA loci. Postoperative intraperitoneal
      administration of IL-10 (100 microg/d, days 0-6) significantly accelerated heart
      graft rejection both in the B10-->C3H (mean survival time [MST] 7.8+/-0.2 days;
      control MST 10.6+/-0.6 days; P<0.05) and the B10.BR-->C3H combination (MST 14.3+/
      0.5 days; control MST 77.7+/-14.4 days). Ex vivo IL-10 perfusion of donor hearts
      for either 15 min or 2 hr did not affect subsequent graft survival. Immunologic
      monitoring of transplanted mice revealed that IL-10 treatment (100 microg/d,
      i.p., days 0-6) increased both the circulating complement-dependent cytotoxic
      (CDC) antibody titer and splenic anti-donor cytotoxic T lymphocyte (CTL) activity
      measured up to 3 weeks posttransplant. These findings indicate that post
      transplant systemic administration of cIL-10 can promote vascularized allograft
      rejection, and that this may reflect stimulation both of B and T cell alloimmune
      responses.

PMID- 8990349
TI  - Donor pretreatment with intravenous prostacyclin versus inhaled nitric oxide in
      experimental lung transplantation.
AB  - The pulmonary vasodilatory effects of prostacyclin (PGI2) were compared with
      inhaled nitric oxide (NO) for donor treatment in an acute double lung
      transplantation model in the rat. The PGI2 group (n=10) received 35 microg/kg
      PGI2 both intravenously and into the flush solution. The NO group (n=10) was
      ventilated before and during perfusion with nitric oxide for an expiratory NO
      concentration of 20 ppm. Both groups were compared with untreated controls
      (n=10). Following cold ischemia of 16 hr the donor lungs were implanted in
      syngeneic recipients via specially designed stents to the left pulmonary artery
      and vein. Separate graft ventilation permitted determination of compliance and
      resistance. During 120 min of reperfusion serial measurements of graft pulmonary
      vascular resistance (PVR) and alveolar arterial oxygen difference (AAD02) were
      obtained. Final graft assessment included weight gain and histological analysis.
      Data are listed as mean+/-SE. The type of donor pretreatment had a definite and
      negative impact on survival (NO: 106+/-6, controls: 116+/-4, PGI2: 120+/-0 min;
      P<0.02) and overall graft function. During reperfusion the compliance was
      significantly reduced in NO (23+/-4) in comparison with controls (34+/-3) and
      PGI2 (50+/-4 ml/cmH2O; P<0.01). The PVR was 785+/-238 in NO, 240+/-60 in controls
      and 181+/-71 mmHg/ml/min in PGI2 (P<0.02). The AaD02 was compromised in NO (486+/
      44) compared with controls (396+/-53) and PGI2 (108+/-34 mmHg; P<0.02). The
      weight increase at the end of reperfusion amounted to 101+/-17% in NO, 98+/-13%
      in controls, and 69+/-7% in PGI2 (P<0.05). Histological analysis showed
      significantly more interstitial edema in the NO group. In conclusion, PGI2
      administration significantly improves global lung function while the inhalation
      of nitric oxide before and during donor perfusion has a detrimental effect on the
      quality of graft preservation.

PMID- 8990350
TI  - The importance of static lung inflation during organ storage: the impact of
      varying ischemic intervals in a double lung rat transplantation model.
AB  - To determine the importance of static lung inflation during storage, graft
      performance was evaluated at different levels of intratracheal pressure and
      varying ischemic intervals. Lewis rat lungs were perfused with low-potassium Euro
      Collins and stored for 4 or 8 hr either in atelectasis (4 hr: group I; 8 hr:
      group IV, respectively) or 13 (group II; V) or 26 cmH2O of airway pressure
      (groups III, VI). Following implantation continuous measurement of alveolar
      arterial oxygen difference (AaDO2*) and pulmonary vascular resistance (PVR) were
      performed. Separate ventilation allowed assessment of mechanical lung function of
      the graft. At the end of reperfusion (120 min) weight gain, histology, and
      phospholipid and protein content in the pulmonary lavage were compared between
      the groups. Despite significant differences in survival at 4 hr of ischemia graft
      function did not differ in groups I to III. In contrast, static inflation had a
      significant impact after 8 hr of ischemia. Lungs stored in atelectasis (group IV)
      could not be reperfused and failed immediately. Survival in group V was 83+/-11
      versus 107+/-7 min in group VI (P<0.05). Compliance at 80 min was 27+/-3 in group
      V and 52+/-6 ml/cmH2O in group VI (P<0.02). Corresponding values for PVR were
      232+/-92 and 112+/-16 mmHg/ml/min, respectively (P<0.05). Less inflation and
      longer ischemia resulted in a reduction of the large to small phospholipid
      aggregate ratio and deterioration of surfactant function in the bubble
      surfactometer. In conclusion, while the amount of static lung inflation may not
      be critical following short ischemia, the performance of the graft improves
      significantly with full inflation (26 cmH2O) following extended ischemia (8 hr).

PMID- 8990351
TI  - Tolerance to rat liver allografts: IV. Acceptance depends on the quantity of
      donor tissue and on donor leukocytes.
AB  - Liver allografts in some rat strains are often spontaneously accepted across a
      complete major histocompatibility barrier without the requirement for
      immunosuppression while other nonliver allografts are rejected. In previous
      studies, we have shown that spontaneous acceptance is dependent on liver
      passenger leukocytes. Depletion of passenger leukocytes by donor irradiation
      allows rejection, with DA recipients of irradiated PVG livers having a median
      survival time (MST) of 16 days. Here we show that, in this model, spontaneous
      acceptance is reconstituted by intravenous injection of donor leukocytes.
      Intravenous injection of 3-5x10(7) PVG liver leukocytes significantly prolonged
      DA survival time (MST=96 days, P=0.026), as did 5x10(7) spleen leukocytes
      (MST>100 days, P=0.002). Deletion of T cells from the reconstituting inoculum
      reduced survival time (MST=78 days, P=0.039), whereas deletion of B cells or
      monocytes/macrophages had no effect on survival time. In contrast, PVG hearts are
      regularly rejected by DA recipients, and PVG liver or spleen leukocytes, even at
      doses of greater than 3x10(8) cells/recipient, were unable to induce heart
      acceptance. To investigate the possibility that acceptance of the irradiated
      liver but not the heart might be due to the large mass of the liver, two kidneys
      and two hearts of PVG origin were transplanted to each DA recipient together with
      1.5x10(8) PVG leukocytes. These organs survived for greater than 200 days,
      thereby showing that a large mass of donor tissue, in association with donor
      leukocytes, leads to acceptance of organs that are rejected if transplanted
      singly. It appears likely that spontaneous liver transplant tolerance is a high
      dose or activation-associated immune phenomenon.

PMID- 8990352
TI  - The effect of ouabain (inhibitor of an ATP-dependent Na+/K+ pump) on the pancreas
      graft during preservation by the two-layer method.
AB  - To clarify how synthesized ATP is utilized to maintain cellular integrity during
      preservation by the two-layer method, we examined the effect of ouabain,
      inhibitor of ATP dependent Na+/K+ pump, on ATP tissue levels, graft weight, and
      vascular endothelial cells during 48 hr preservation by the two-layer method and
      pancreatic tissue perfusion and graft survival after transplantation in a canine
      model. Ouabain treatment did not affect ATP production but prevented its
      utilization by the sodium pump, and actually significantly increased ATP levels
      and decreased the weight loss of the graft. In addition, ouabain caused a
      significant increase of nuclear trypan-blue staining in vascular endothelial
      cells and a significant decrease of pancreatic tissue perfusion at reperfusion.
      Consequently, the grafts did not survive. We conclude that the two-layer method
      allows sufficient synthesis of ATP to drive the sodium pump and maintains
      membrane integrity of parenchymal cells and vascular endothelial cells, thus
      extending the period of preserved pancreatic viability.

PMID- 8990353
TI  - The use of a novel monitoring apparatus and modified Belzer hydroxyethyl starch
      perfusate for analysis of glomerular filtration during hypothermic perfusion
      preservation.
AB  - The present study describes an experimental model for measurement of glomerular
      filtration during hypothermic perfusion preservation (HPP). To facilitate
      glomerular filtration during HPP, perfusate oncotic pressure was reduced by
      lowering the concentration of hydroxyethyl starch. Lewis rats underwent HPP at a
      mean perfusion pressure of 40-46 mmHg. An isograft model was used to demonstrate
      that retrieval and preparation for HPP did not impact adversely on renal
      function. Total cold ischemic time (CIT) consisted of the time from retrieval and
      preparation for perfusion (2 hr) added to the time of HPP. Tubular function
      studies demonstrated identical concentrations of Na+ and iohexol in ureteral
      effluent (UE) compared with circulating perfusate and, as such, established that
      UE flow represented a direct measure of glomerular filtration. Glomerular
      filtration rate (GFR) was then monitored during HPP by collecting UE in a beaker
      housed within a computerized Mettler balance system. GFR evolved in a
      characteristic, biphasic pattern during HPP, increasing from baseline values to
      reach a peak level at 4.8+/-0.3 hr of CIT and declining progressively thereafter.
      At 2.5 hr, time of peak values, 10 hr, 19.5 hr, and 24 hr of CIT, GFR values were
      29+/-6 microl/min, 39+/-7 microl/min, 20+/-4 microl/min (n=15; P<0.01), 7+/-2
      microl/min (n=14; P<0.001), and 14+/-6 microl/min (n=5), respectively. Intrarenal
      perfusate flows at the same time intervals were 4180+/-292 microl/min, 4083+/-290
      microl/min, 3577+/-294 microl/min (P=NS), 1948+/-393 microl/min (P<0.001), and
      2175+/-743 microl/min, respectively. Filtration fraction (FF) initially changed
      in parallel to glomerular filtration. Thereafter, FF either declined at a
      disproportionately slow rate compared with GFR (n=8) or increased rapidly (n=7).
      The data suggest that (1) primary change(s) in glomerular dynamics occur during
      HPP and (2) declining perfusate flow during the later stages of HPP reflects
      increasing renal vascular resistance localized at a postglomerular level. The
      data provide an experimental basis for investigating the clinical utility of
      monitoring glomerular filtration during HPP.

PMID- 8990354
TI  - Apyrase administration prolongs discordant xenograft survival.
AB  - Platelet thrombi and vascular inflammation are prominent features of discordant
      xenograft rejection. The purinergic nucleotides ATP and ADP, which are secreted
      from platelets and released by injured endothelial cells (EC), are important
      mediators of these reactions. Quiescent EC express the ectoenzyme ATP
      diphosphohydrolase (ATPDase; an apyrase), which exerts an important
      thromboregulatory function by hydrolyzing both ATP and ADP. We have shown that
      ATPDase activity is rapidly lost from the surface of the EC following ischemia
      reperfusion injury and during xenograft rejection. The aim of this study was to
      supplement ATPDase activity within xenografts by infusion of soluble apyrases,
      and thereby validate the importance of local ATPDase activity in the modulation
      of xenograft rejection. Lewis rats underwent heterotopic cardiac xenografting
      from guinea pigs and apyrase was administered intravenously (200 U/kg) as a
      single dose to evaluate effects on hyperacute rejection (HAR). This initial dose
      was followed by a continuous apyrase infusion (8.0 U/kg/hr) directly into the
      graft aorta in combination with systemic cobra venom factor (CVF) administration
      to deplete complement when delayed xenograft rejection (DXR) was studied.
      Functional apyrase levels in vivo were assessed by the capacity of blood samples
      taken at the time of surgery and rejection to inhibit platelet aggregation in
      vitro. Apyrase administration significantly prolonged graft survival in HAR and
      DXR. Functional assays showed inhibition of platelet aggregation suggesting
      effective systemic antiaggregatory effects of the administered apyrases.
      Histologic studies showed that apyrase administration abrogated local platelet
      aggregation and activation in HAR and DXR. Our data demonstrate that local
      administration of apyrase prolonged discordant xenograft survival. These
      observations emphasize the potential importance of purinergic mediators in
      platelet activation during xenograft rejection.

PMID- 8990355
TI  - A randomized, prospective multicenter pharmacoepidemiologic study of cyclosporine
      microemulsion in stable renal graft recipients. Report of the Canadian Neoral
      Renal Transplantation Study Group.
AB  - BACKGROUND: The safety, tolerability, and pharmacokinetics of conventional
      cyclosporine (ConCsA) and cyclosporine microemulsion (MeCsA) were compared under
      conditions of normal clinical practice in a prospective, randomized,
      concentration-controlled, pharmacoepidemiologic study. METHODS: Between September
      1994 and March 1995, 1097 stable renal transplant recipients in 14 Canadian
      centers were randomized 2:1 to treatment with MeCsA or ConCsA. Patients were
      commenced on each study drug at a dose equal to their previous therapy with
      ConCsA, and the dose was adjusted to maintain predose whole blood cyclosporine
      concentrations within the therapeutic range established for each center.
      Prednisone and azathioprine were continued unless dose adjustment was required
      for clinical reasons. RESULTS: The mean cyclosporine concentration was comparable
      in both treatment groups at all time points throughout the 6 months of follow-up.
      The mean dose of cyclosporine was 3.6 mg/kg/day in both treatment groups at entry
      to the study, and declined by 0.3% and by 2.8% in patients receiving ConCsA and
      MeCsA, respectively. The nature and severity of adverse events were similar in
      both treatment groups, but there was a transient increase in neurological and
      gastrointestinal complications in the group receiving MeCsA within the first
      month after conversion (P<0.05). Serum creatinine and creatinine clearance did
      not change in either treatment group throughout the study. Biopsy-proven acute
      rejection occurred in three patients (0.8%) receiving ConCsA and in seven
      patients (0.9%) receiving MeCsA, with non-histologically proven acute rejection
      in an additional three patients (0.8%) receiving ConCsA and five patients (0.6%)
      receiving MeCsA (P=NS). Serum creatinine rose transiently in 35 patients (9.8%)
      receiving ConCsA and 138 patients (18.7%) receiving MeCsA (P<0.05) and resolved
      either spontaneously or after a reduction in the cyclosporine dose. One graft was
      lost in the MeCsA group due to irreversible rejection, and seven patients died,
      three in the group receiving ConCsA and four of those receiving MeCsA (P=NS).
      Absorption of cyclosporine was more rapid and complete from MeCsA than from
      ConCsA during the first 4 hr of the dosing interval, resulting in almost 40%
      greater exposure to the drug (P<0.001). There was close correlation between area
      under the time-concentration curve (AUC) over the first 4 hr of the 12-hr dosage
      interval and AUC over the entire 12-hr dosage interval for both formulations,
      making AUC over the first 4 hr a good predictor of total cyclosporine exposure.
      Using this parameter, patients with low absorption randomized to receive MeCsA
      showed a marked increase in drug exposure by months 3 and 6, whereas there was no
      change in those who continued on ConCsA. A limited sampling strategy utilizing
      samples at the predose and postdose trough levels provided an excellent
      correlation with drug exposure, particularly for patients receiving MeCsA
      (r2=0.94 MeCsA vs. r2=0.89 ConCsA). CONCLUSIONS: MeCsA appears to be a safe and
      effective therapy in stable renal transplant patients and provides superior and
      more consistent absorption of cyclosporine when compared with ConCsA. Transient
      toxicity after conversion to MeCsA occurs in some patients, and may reflect the
      increased exposure to cyclosporine. Use of a limited sampling approach combining
      trough and 2-hr postdose concentrations may provide an effective way to monitor
      this exposure.

PMID- 8990357
TI  - Clinical hepatitis after transplantation of hepatitis C virus-positive kidneys:
      HLA-DR3 as a risk factor for the development of posttransplant hepatitis.
AB  - BACKGROUND: Exposure to hepatitis C virus (HCV) and subsequent infection after
      renal transplantation lead to significant clinical hepatitis in approximately 50%
      of graft recipients. METHODS: One hundred thirty-two consecutive renal
      allotransplant patients, who underwent transplantation of kidneys from HCV
      positive cadaveric donors, were studied to investigate the relationship between
      donor and recipient HLA type and the risk of developing clinical hepatitis.
      Specific attention was directed toward the DR3 and DR4 alleles, as these had
      previously been associated with worse prognoses in autoimmune and viral
      hepatitis. RESULTS: Overall, 42% of patients receiving kidneys from donors
      seropositive for HCV developed clinical hepatitis. This was unrelated to
      preoperative recipient HCV serum reactivity (P=0.65). Patients receiving kidneys
      from seropositive donors with HCV RNA as detected by PCR were more likely to
      develop hepatitis than those receiving kidneys from PCR-negative donors (56% vs.
      11%; P=0.005). The presence of the DR3 allele was associated with a significant
      risk of clinical hepatitis (P=0.025); 80% of DR3-positive recipients (n=34)
      progressed to hepatitis compared with 42% of DR3-negative patients. No other
      recipient HLA type was significantly related to prognosis. All patients receiving
      a donated kidney that expressed the B41 allele developed hepatitis, compared with
      55% of recipients of non-B41 grafts (P=0.039). No association between the
      development of clinical hepatitis and HLA compatibility was found. CONCLUSIONS:
      These results suggest that both HLA type and viral presence as assayed by
      polymerase chain reaction, influence the risk of disease progression after
      transplantation of HCV-positive kidneys. Application of these associations may
      decrease the relative risk of a recipient contracting HCV hepatitis after
      cadaveric renal transplantation.

PMID- 8990356
TI  - Tacrolimus in pediatric renal transplantation.
AB  - Tacrolimus was used as the primary immunosuppressive agent in 69 pediatric renal
      transplantations between December 17, 1989, and June 30, 1995. Children
      undergoing concomitant or prior liver and/or intestinal transplantation were
      excluded from analysis. The mean recipient age was 10.3+/-5.0 years (range, 0.7
      17.5 years). Seventeen (24.6%) children were undergoing retransplantation, and
      six (8.7%) had a panel reactive antibody level of 40% or higher. Thirty-nine
      (57%) cases were with cadaveric kidneys, and 30 (43%) were with living donors.
      The mean donor age was 28.0+/-14.7 years (range, 1.0-50.0 years), and the mean
      cold ischemia time for the cadaveric kidneys was 27.0+/-9.4 hr. The antigen match
      was 2.7+/-1.2, and the mismatch was 3.1+/-1.2. All patients received tacrolimus
      and steroids, without antibody induction, and 26% received azathioprine as well.
      The mean follow-up was 32+/-20 months. One- and 4-year actuarial patient survival
      rates were 100% and 95%. One- and 4-year actuarial graft survival rates were 99%
      and 85%. The mean serum creatinine level was 1.2+/-0.8 mg/dl, and the calculated
      creatinine clearance was 82+/-26 ml/min/1.73 m2. The mean tacrolimus dose was
      0.22+/-0.14 mg/ kg/day, and the level was 9.5+/-4.8 ng/ml. The mean prednisone
      dose was 2.1+/-4.9 mg/day (0.07+/-0.17 mg/kg/day), and 73% of successfully
      transplanted children were off prednisone. Seventy-nine percent were not taking
      any antihypertensive medications. The mean serum cholesterol level was 158+/-54
      mg/dl. The incidence of delayed graft function was 4.3%. The incidence of
      rejection was 49%, and the incidence of steroid-resistant rejection was 6%. The
      incidence of rejection decreased to 27% in the most recent 26 cases (January 1994
      through June 1995). The incidence of new-onset diabetes was 10.1%; six of the
      seven affected children were able to be weaned off insulin. The incidence of
      cytomegalovirus disease was 13%, and that of posttransplant lymphoproliferative
      disorder was 10%; the incidence of posttransplant lymphoproliferative disorder in
      the last 40 transplants was 5% (two cases). All of the children who developed
      posttransplant lymphoproliferative disorder are alive and have functioning
      allografts. Based on this data, we believe that tacrolimus is a superior
      immunosuppressive agent in pediatric renal transplant patients, with excellent
      short- and medium-term patient and graft survival, an ability to withdraw
      steroids in the majority of patients, and, with more experience, a decreasing
      rate of rejection and viral complications.

PMID- 8990358
TI  - Evaluation of voiding cystourethrography prior to renal transplantation.
AB  - In many centers, voiding cystourethrography is a routine part of
      pretransplantation assessment of the lower urinary tract. To assess the value of
      this investigation, a retrospective review of transplant candidates evaluated in
      our center over 2 years was undertaken. A total of 517 patients were fully
      evaluable. Only 13 voiding cystourethrograms (VCUGs) (2.5%) of 517 were found to
      be abnormal. Three patients with reflux alone did not require intervention before
      transplantation. Four patients with decreased bladder capacity underwent
      hydrodistention. Two patients increased their capacity to over 150 ml and two
      patients failed distention, one requiring an ileal conduit and the other
      requiring an augmentation cystoplasty. Three patients had increased postvoid
      residual (PVR). Two patients started clean intermittent catheterization. One
      required prostate resection for benign prostatic hypertrophy. One patient with
      reflux and decreased bladder capacity refused treatment. One patient with reflux
      combined with increased PVR started clean intermittent catheterization and was
      cleared for transplant surgery. One patient with decreased bladder capacity and
      increased PVR had a stroke and was excluded from transplantation. All 13 patients
      with abnormal VCUGs had a prior urologic history. In total, only 56 of 517
      patients evaluated had a prior urological history. Each VCUG costs approximately
      $500. Limiting VCUG studies to those patients with a prior urological history
      would have resulted in a significant cost savings. Hence, we recommend that only
      patients with a prior urological history should undergo this costly and often
      distressing examination.

PMID- 8990360
TI  - Histologic findings in islets of whole pancreas allografts: lack of evidence for
      recurrent cell-mediated diabetes mellitus.
AB  - Cell-mediated cytotoxicity directed toward pancreatic islets plays a significant
      role in the pathogenesis of type 1 diabetes mellitus. Histologically, autoimmune
      insulitis appears as mononuclear infiltrates that precede actual beta cell loss.
      Experimental studies by Bartlett et al. on the BB rat model suggest that whole
      pancreas transplants are not susceptible to recurrent autoimmune diabetes. To
      test this hypothesis on clinical grounds, we evaluated the islets in
      pancreatectomies and percutaneous needle biopsies from 55 whole pancreas
      allografts. In this material, islet inflammation was never seen independently of
      allograft rejection, but was always associated with inflammation of the
      surrounding acinar structures. The degree of islet inflammation and the
      occasional presence of islet necrosis correlated well with the degree of
      rejection and only occurred in the higher grades of the latter (grades III-V). We
      did not observe isolated insulitis as a histological indication of selective cell
      mediated cytotoxicity against beta cells.

PMID- 8990359
TI  - Chronic viral hepatitis enhances the risk of infection but not acute rejection in
      renal transplant recipients.
AB  - To assess the impact of chronic viral hepatitis on host immune response, we
      analyzed the incidence of acute rejection and the frequency of infections in 86
      patients infected with hepatitis B and C viruses and had developed clinical
      evidence of chronic liver disease and 1283 control patients who were transplanted
      at our center during the same period, but had no evidence of chronic viral
      hepatitis. To compare the mean number of rejections and the mean number of
      infections between the two groups, we used multivariate linear regression
      analysis, which allowed us to adjust simultaneously for the effects of 10 other
      risk variables with potential impact on graft rejection and posttransplant
      infection. During a mean follow up of 5.3+/-5.2 years, 62% of hepatitis patients
      and 54% of control patients had experienced an acute rejection (P=NS). The mean
      rejections/patient in the hepatitis group was 1.3+/-0.14 versus 1.03+/-0.03 in
      control (P=NS). In the linear regression analysis, the number of acute rejections
      in the hepatitis group was 0.16 higher than in control (P=NS). With reference to
      infection, 84% of hepatitis patients experienced an infectious complication in
      the posttransplant period, compared with 75% in the control (P=0.05). The mean
      number of infections/patient was 5.7+/-0.73 in the hepatitis group compared with
      3.9+/-0.14 in the control group (P=0.002). The linear regression model had shown
      that the hepatitis group had a relative increase of 1.18 infections/pt, compared
      with control. Of the different sites of infection, the hepatitis group had a
      significant increase in bloodstream (0.48+/-0.08 vs. 0.25+/-0.02) P=0.003;
      pulmonary (0.60+/-0.09 vs. 0.38+/-0.03) P=0.03; and CNS infections (0.08+/-0.03
      vs. 0.02+/-0.004) P=0.05 compared with control. Among the different
      microorganisms causing infection, the hepatitis patients had a significant
      increase in gram negative bacterial infections compared with the control group
      (74% vs. 61%) P=0.04. Our data suggest that chronic viral hepatitis is associated
      with a significant increase in overall infections, and that of potentially fatal
      infections involving CNS, lungs and bloodstream. Since there is no significant
      increase in the rate of graft rejection, one could consider a cautious reduction
      in the doses of maintenance immunosuppressive agents in renal transplant patients
      with chronic viral hepatitis. The reduced immunosuppression may in turn lower the
      death rate from sepsis and progressive hepatic failure.

PMID- 8990361
TI  - Graft loss following liver transplantation in patients with chronic hepatitis C.
AB  - Liver disease due to hepatitis C (HCV) is an increasingly frequent indication for
      orthotopic liver transplantation (OLT). The aim of the current study was to
      analyze the causes of graft loss following OLT for chronic hepatitis C and the
      longterm outcome following retransplantation in a large university program.
      Between January 1990 and December 1995, 1183 patients underwent primary OLT at
      our center. In 304 patients, HCV was diagnosed by seropositivity and/or
      polymerase chain reaction. Fifty-six (18.4%) of these patients underwent
      retransplantation. The 36 patients retransplanted for primary non-function were
      excluded from further analysis. The other indications for regrafting (>30 days
      following primary transplant) included hepatic artery thrombosis (5), chronic
      rejection (4), severe HCV recurrence (5), and other etiologies (6). The
      cumulative survival rates for the 248 patients who received 1 OLT (group 1) were
      84% after one year and 75% after three years. The corresponding rates for the 20
      non-PNF patients who were retransplanted (group 2) were 60% and 43%, respectively
      (P<.0001). Moreover, logistic regression analysis confirmed that patients in
      group 2 were more than 4 times likely to die than patients in group 1 (P<.0034;
      risk ratio, 4.2; 95% confidence interval 1.61 to 11.37). Patients undergoing
      retransplantation had a high incidence of serious infectious complications
      leading to mortality. Two additional patients with severe recurrent HCV died
      awaiting liver retransplantation. Eight of the 304 total patients (2.6%)
      transplanted for chronic HCV developed graft failure secondary to HCV recurrence
      and 6 of the 8 were retransplanted; 3 of the 6 patients retransplanted are alive
      without evidence of histologic recurrence (mean follow-up less than 1 year). In
      summary, despite the high frequency of recurrent histologic evidence of HCV
      following primary OLT (70% at 3 years), graft loss attributable solely to HCV is
      an infrequent finding. Retransplantation per se is a risk factor for a fatal
      outcome, and the indication for reOLT does not appear to impact ultimate outcome.
      Serious infectious complications were the leading cause of mortality in patients
      retransplanted. Furthermore, given the indolent natural history of HCV, longer
      follow-up is necessary to determine the ultimate rate of graft loss due to HCV
      recurrence.

PMID- 8990362
TI  - Fibrosis in chronic rejection of human liver allografts: expression patterns of
      transforming growth factor-TGFbeta1 and TGF-beta3.
AB  - Activation and transformation of lipocytes (Ito cells, stellate cells) into alpha
      actin-positive myofibroblast-like cells is an essential step in the initiation of
      liver fibrosis. Transforming growth factor-beta (TGF-beta) is considered an
      important mediator of this process. In order to determine mechanisms of fibrotic
      deposition in a hepatic transplant setting, we analyzed 10 chronically rejected
      human liver allografts for the expression of extracellular matrix (ECM)
      molecules, myofibroblast-like cells (alpha-actin), macrophages, and TGF-beta1 and
      -beta3. Using single- and double-immunohistochemical staining techniques, all
      specimens investigated showed increased deposition of the ECM proteins
      fibronectin, tenascin, undulin, and collagen VI with a characteristic
      densification especially in pericentral areas. Likewise, strong accumulation of
      alpha-actin-positive cells and TGF-beta1-expressing macrophages was observed in
      the same fields, supporting the concept of lipocyte activation/transformation and
      subsequent ECM production fostered by macrophage-derived TGF-beta1. In contrast,
      TGF-beta3 was found to be mainly expressed by a markedly increased number of
      lipocytes. Interestingly, distribution of TGF-beta3 corresponded to that of
      tenascin, an ECM molecule known to be involved in early matrix organization,
      suggesting that TGF-beta3 may likewise act mainly in early stages of
      fibrogenesis. Furthermore, TGF-beta3 restriction to high numbers of a single cell
      type (i.e., lipocytes) implied a possible role in cell proliferation through
      autocrine loops. In conclusion, fibrosis in chronic rejection seems to follow
      similar mechanisms as in non-transplanted livers but additionally suggests
      differential temporal and functional roles for the TGF-beta isoforms 1 and 3 in
      the course of a multistep process leading to lipocyte transformation and ECM
      production.

PMID- 8990363
TI  - Influence of donor and recipient gender on the outcome of liver transplantation.
AB  - BACKGROUND: Gender is currently not a criterion in the allocation of scarce donor
      organs. The purpose of this study was to determine the effects of gender on
      patient and graft survival, incidence of rejection, and postoperative
      complications after orthotopic liver transplantation. METHODS: During a 10-year
      period, 1138 liver transplants were performed on 1010 adult patients at Baylor
      University Medical Center. In this study, 994 patients with at least 6 months of
      posttransplant follow-up were reviewed. The four combinations of gender match and
      mismatch included: group 1, donor female to recipient female (n=229); group 2,
      donor female to recipient male (n= 126); group 3, donor male to recipient female
      (n=247); and group 4, donor male to recipient male (n=392). These groups were
      evaluated for patient survival, graft survival, episodes of rejection, incidence
      of chronic rejection, and postoperative complications. RESULTS: All groups were
      similar with respect to recipient age, underlying medical condition, incidence of
      bacterial and viral infections, postoperative biliary complications, and the
      incidence of chronic rejection. Female recipients had the highest incidence of
      early rejection (0-6 months, 70%) compared with male recipients (60%, P<0.039).
      Postoperative vascular complication (10%) was highest in group 3 (P<0.01). The
      two-year graft survival rate for groups 1, 3, and 4 was 76.2%, 75.6%, and 73.5%,
      respectively. Group 2, donor female to recipient male, had a 2-year graft
      survival rate of 55.9% (P<0.0001). This finding is not explained by the incidence
      of early rejection. Chronic rejection does not appear to be contributory. The
      mean donor age for groups 1, 3, and 4 was 35.7, 25.8, and 30.4 years,
      respectively. The mean donor age for group 2 was slightly older, at 41.6 years
      (P<0.0001). This difference, while statistically significant, is of unknown
      clinical relevance. A multivariate analysis controlling for donor age confirmed
      the decreased graft and patient survival rates in the donor female to recipient
      male group. CONCLUSIONS: The decreased graft survival rate in male recipients of
      female livers warrants further study and may argue for modifying the current
      management of adult male liver transplant recipients.

PMID- 8990364
TI  - Outcome of patients with renal insufficiency undergoing liver or liver-kidney
      transplantation.
AB  - Renal insufficiency (RI) is a common finding with end-stage liver disease. RI is
      generally not regarded as a contraindication to liver transplantation. However,
      the impact of RI on outcome following transplantation and the role of combined
      liver-kidney transplant are not well understood. The effect of RI on patients
      with fulminant hepatic failure (FHF) or chronic liver disease (cirrhosis) was
      investigated using the National Institute of Diabetes and Digestive and Kidney
      Diseases (NIDDK) Liver Transplantation Database. Patients were analyzed based on
      the presence of RI, defined as creatinine >1.6 mg/dl, or on dialysis. Patients
      undergoing liver-kidney transplantation were analyzed separately. For patients
      with FHF, the RI group had a lower patient survival rate at 1 year (50% vs. 83%,
      P=0.04) and tended to have a lower graft survival rate (50% vs. 71%). Stay in the
      intensive care unit (ICU) was prolonged in the RI group but hospital stay was
      not. Among patients with cirrhosis, RI did not affect patient survival, except
      for patients on dialysis or those with liver-kidney transplants. One-year patient
      and graft survival rates were 65% and 60% for the dialysis group, 74% and 70% for
      the liver-kidney transplant group, 89% and 86% for RI patients not on dialysis,
      and 89 and 84% for non-RI patients. ICU and hospital stays were prolonged for all
      of the RI groups compared with the non-RI patients. Patients with RI had higher
      rates of posttransplant dialysis; however, the differences tended to equalize
      after 4 weeks. We conclude that RI in FHF and RI requiring dialysis or liver
      kidney transplantation in cirrhosis predict lower posttransplant patient and
      graft survival rates. Patients with RI have longer hospital and ICU stays and an
      increased need for dialysis, which likely increases the cost of transplantation.
      Whether liver-kidney transplantation improves outcome and thus represents an
      appropriate use of cadaver kidneys requires further study.

PMID- 8990365
TI  - The impact of a positive crossmatch upon outcome after liver transplantation.
AB  - Recent reports have shown that liver allografts transplanted against a positive
      lymphocytotoxic crossmatch (CDC+) are susceptible to an increased frequency of
      rejection, and decreases in patient and graft survival. The implication of a
      positive flow cytometric crossmatch (FCXM+) in liver transplantation remains
      controversial. The purpose of this study was to determine what impact a
      pretransplant IgG crossmatch due to CDC+ or FCXM+ had upon the clinical outcome
      following liver transplantation. Preoperative crossmatch status was determined
      prospectively in 110 consecutive liver transplants performed between July 1991
      and January 1995. Allografts were divided into three groups: negative crossmatch
      (NXM), positive flow cytometric crossmatch FCXM+, and positive lymphocytotoxic
      crossmatch CDC+. Crossmatch status did not impact patient or graft survival.
      Actuarial patient survival was similar between groups at 12 months (88% vs. 95%
      vs. 92%, NXM vs. FCXM+ vs. CDC+) and 24 months (81% vs. 93% vs. 92%, NXM vs.
      FCXM+ vs. CDC+) (P=0.1938). Actuarial allograft survival was similar between
      groups at 12 months (76% vs. 93% vs. 85%, NXM vs. FCXM+ vs. CDC+) and 24 months
      (76% vs. 89% vs. 85%, NXM vs. FCXM+ vs. CDC+) (P=0.0738). CDC+ allografts had a
      significant increase in early rejection episodes compared with NXM (46% vs. 7%,
      CDC+ vs. NXM) (P=0.003) or FCXM+ allografts (46% vs. 10%, CDC+ vs. FCXM+)
      (P=0.006). CDC+ allografts experienced significantly more rejection episodes per
      year than NXM (53% vs. 20%, CDC+ vs. NXM) (P=0.015) or FCXM+ allografts (53% vs.
      23%, CDC+ vs. FCXM+) (P=0.02). CDC+ allografts had a significant increase in
      numbers of additional nonconventional therapeutic interventions compared to NXM
      allografts (0.9+/-0.5 vs. 0.2+/-0.1, CDC+ vs. NXM) (P=0.039). The presence of
      cytotoxic antibodies pretransplantation is associated with increased incidences
      of early rejection, and rejection episodes per year. With careful monitoring and
      aggressive therapeutic interventions the presence of cytotoxic antibodies are not
      deleterious to patient or liver allograft survival.

PMID- 8990366
TI  - A microemulsion of cyclosporine without intravenous cyclosporine in liver
      transplantation.
AB  - A microemulsion formulation of cyclosporine (CsA) has improved absorption
      compared with the original form. The purpose of this case control study was to
      assess the safety and efficacy of the microemulsion without intravenous CsA for
      induction immunosuppression in adult liver transplantation. Twenty-one
      consecutive patients receiving induction immunosuppression with the microemulsion
      15 mg/kg/day were compared with 20 patients receiving intravenous CsA and the
      original oral form. Both groups received the same dose of methylprednisilone.
      Twenty of 21 patients receiving the microemulsion required no intravenous CsA to
      achieve target CsA levels. All patients receiving the original form received
      initial intravenous CsA. There was no difference in trough CsA levels between the
      two groups at 24 and 48 hours. The microemulsion group had 24 hr and 48 hr trough
      CsA levels of 227+/-15 and 520+/-300 ng/ml by monoclonal RIA while the
      intravenous CsA group had 24 and 48 hr trough levels of 293+/-18 and 405+/-91
      ng/ml. CsA levels analyzed by HPLC were 20% lower than by RIA. The frequency of
      adverse events resulting in reduction of drug dosage was similar for the
      microemulsion and the original form: neurotoxicity (23 vs. 40%, P=.30);
      nephrotoxicity (25 vs. 45%, P=.32), and no patients required dialysis. There was
      no difference in septic complications. One patient required discontinuation of
      the microemulsion in an attempt to reverse severe neurotoxicity. A total of 75%
      of microemulsion patients were rejection free at 3 months while only 35% of CsA
      patients remained rejection free (P=0.02). These data suggest that the use of the
      microemulsion without intravenous CsA in liver transplantation is safe and
      efficacious, and may result in decreased episodes of acute rejection.

PMID- 8990367
TI  - Recurrence of nonalcoholic steatohepatitis following liver transplantation.
AB  - Patients with nonalcoholic steatohepatitis (NASH) may develop progressive liver
      dysfunction necessitating liver transplantation (OLT). We report the incidence of
      recurrent disease and outcome in patients undergoing OLT for NASH. Patients
      transplanted for NASH were identified according to pretransplant and explant
      liver histology. Patients with significant alcohol consumption were excluded.
      Medical records were reviewed to extract pre- and posttransplant data, including
      sequential body weight, biochemistry, and graft histology. Of 622 liver explants,
      eight patients had features consistent with NASH. All patients were female with a
      median age of 58. Seven patients were diagnosed with NASH preoperatively,
      including three who had undergone jejunoileal bypass. One patient was diagnosed
      as cryptogenic cirrhosis. At a median of 15 months following OLT, all of the
      eight patients were alive with no graft failure. Six patients developed
      persistent fatty infiltration in their graft, three of whom had accompanying
      hepatocellular degeneration, consistent with a diagnosis of recurrent NASH. In
      two patients, transition from mild steatosis to steatohepatitis and early
      fibrosis was observed over one to two years. The patients who did not develop
      recurrent steatosis had significant weight loss following transplantation,
      although the length of follow-up was relatively short. Patients undergoing OLT
      for NASH may develop recurrent steatosis shortly after transplantation, with
      possible progression to steatohepatitis and fibrosis. Although longer follow-up
      is necessary to determine the eventual prognosis related to the recurrent fat and
      fibrosis in the graft, patients with endstage liver disease due to NASH should be
      considered good candidates for OLT.

PMID- 8990368
TI  - Allogeneic transplantation for advanced leukemia: improved short-term outcome
      with blood stem cell grafts and tacrolimus.
AB  - We have evaluated the use of blood stem cell grafts for rapid hematopoietic
      recovery and tacrolimus (FK506) as GVHD prophylaxis to reduce early mortality
      after allogeneic transplantation. Eighty-five adults with advanced leukemia
      received high-dose thiotepa, busulfan, and cyclophosphamide as a preparative
      regimen in a prospective Phase II study. All donors were HLA-matched and related.
      Marrow (BMT) was used for 44 patients and filgrastim-mobilized blood stem cells
      (SCT) for 41 patients. GVHD prophylaxis consisted of cyclosporine (CsA) or FK506
      with methotrexate (MTX) or methylprednisolone (MP). The median time to neutrophil
      recovery was earlier after SCT than after BMT (day 10 vs. 17, P<0.001), but this
      was due to the selective use of MTX only in the BMT patients. The risk of grades
      2-4 GVHD was lower with FK506 than with CsA (16% vs. 45%, P=0.02) and was the
      same for SCT recipients as for BMT recipients (33% vs. 34%). Regimen-related
      toxicity was significantly lower after SCT than after BMT but did not differ
      between the FK506 and CsA patients. In comparison with those receiving the
      standard transplant (BMT with CsA and MTX), only the SCT recipients using FK506
      and MP had a significantly higher survival at day 180 posttransplant (84% vs.
      53%, P=0.014). In multivariate analyses, use of FK506 was associated with a lower
      risk of treatment-related mortality and a higher survival at day 180, while the
      diagnosis of acute lymphoblastic leukemia was associated with a higher risk of
      treatment-related mortality. These data suggest that the use of blood stem cell
      grafts and FK506 can reduce the early mortality after allogeneic transplantation
      for advanced leukemia.

PMID- 8990369
TI  - Sequential measurement of peripheral blood allogeneic microchimerism levels and
      association with pulmonary function.
AB  - We have shown in lung recipients that high levels of peripheral blood allogeneic
      microchimerism at 12 to 18 months posttransplant correlated with donor antigen
      specific hyporeactivity (i.e., decreased proliferative response to donor antigen
      in MLC while response to 3rd-party cells remains unchanged); both parameters
      correlated with an obliterative bronchiolitis (OB)-free state. We have expanded
      these studies to determine any association of sequential microchimerism levels
      with concomitant clinical events. In this preliminary study of 7 lung recipients,
      we used limiting-dilution PCR to quantify peripheral blood microchimerism at
      serial timepoints ranging from 3 to >48 months posttransplant. These levels were
      compared with a variety of immunologic and clinical parameters: acute rejection,
      CMV infection, OB, donor antigen-specific hyporeactivity, and pulmonary function.
      Pulmonary function was measured per the International Society of Heart and Lung
      Transplantation: "current FEV1/ baseline FEV1" (FEV1: forced expiratory volume in
      1 second). Of the clinical parameters, the association between microchimerism and
      pulmonary function was the most striking. We observed dynamic patterns of
      peripheral microchimerism, which reflected the general rise and fall of FEV1. In
      all 7 recipients, chimerism and FEV1 were high very early posttransplant, then
      dropped at various rates and to various degrees. After its initial decline,
      microchimerism increased with FEV1 for the 1 hyporesponsive recipient; for the
      other 6 recipients, both values declined. These results illustrate, for the first
      time, that the fluctuation of peripheral blood microchimerism levels is
      associated with the recipient's clinical condition.

PMID- 8990370
TI  - HLA-DR and DQ typing by polymerase chain reaction using sequence-specific primer
      mixes reduces the incidence of phenotypic homozygosity (blanks) over serology.
AB  - Because of the inherent difficulties in allele assignment with HLA-DR serological
      typing, in 1993 our organ procurement organization-based HLA laboratory replaced
      serology with the molecular method of polymerase chain reaction using sequence
      specific primer mixes (PCR-SSP) to type for DR and DQ at a resolution level
      equivalent to that of serologically defined antigens. In this study, we compared
      the incidence of DR blanks, where allocative homozygosity occurred, and graft
      outcome during our serology epoch (1987-1993) with that of our molecular epoch
      (1993-1996). The incidence of DR blanks by PCR-SSP (17.0%; 138/1101) was
      significantly lower (P<0.005) than in the serology epoch (21.5%; 569/2647).
      Although DQ is not a component of the allocation algorithm, the incidence of
      blanks in the molecular era (21.9%; 196/895) was 46% lower (P<0.001) than in the
      serology epoch (40.8%; 931/2277). Graft survival in 163 cadaveric renal
      transplant recipients for whom molecular DR allocation occurred (patient and
      donor were molecularly typed) showed that PCR-SSP typing had no significant
      effect on 2.5-year graft survival for patients mismatched for 0 (97%), 1 (90%),
      or 2 (94%) HLA-DR antigens (P=0.4; log-rank). In conclusion, molecular typing
      lowered the rate of DR and DQ blanks, but molecular matching for HLA DR and DQ
      did not influence graft outcome at 2.5 years.

PMID- 8990371
TI  - Outcome of children with pulmonary hypertension referred for lung or heart and
      lung transplantation.
AB  - We reviewed our institutional experience with 24 children with pulmonary
      hypertension, who were referred for lung or heart and lung transplantation.
      Diagnosis, age, and previously published predictive survival scores calculated at
      the time of referral were analyzed as predictors of pretransplant death. Among
      the 24 children, 7 did not meet criteria for listing and 17 were listed for
      transplantation. Of those listed, eight died waiting, two await transplantation,
      and seven were transplanted and are alive and well 7-20 months after
      transplantation. Poor functional status (New York Heart Association class 3 or 4)
      at the time of referral was significantly associated with death before transplant
      (P=0.05) in univariate analysis. Analysis of the predictive scores was possible
      in 21 of 24 patients; lower predictive scores were significantly associated with
      death before transplantation and shorter duration of survival without
      transplantation in univariate analysis. Multivariate analysis (Cox regression)
      confirmed that lower scores were significantly associated with poor survival. We
      conclude that children with pulmonary hypertension are often referred for
      transplantation too late in the course of their disease. Early complete
      hemodynamic evaluation before the onset of severe symptoms, followed by serial
      evaluations of disease progression and consultation with a transplant center,
      should result in earlier, more appropriate time of listing and improved survival.
      A systematic study of pretransplant mortality among all children listed for lung
      transplantation would provide a basis for clinical decision making and policies
      affecting organ allocation.

PMID- 8990372
TI  - Who pays for failed organ procurement and what is the cost of altruism?
AB  - Our objective was to define medical complications and financial charges generated
      during the care of potential solid organ donors who fail to donate after consent
      has been obtained. A retrospective review of financial and medical records of
      potential organ donors was done at an urban level 1 trauma center. Total hospital
      stay (T1+T2) for the group was broken down into the interval between admission
      and diagnosis of lethality (T1) and between diagnosis of lethality and death
      (T2). Medical complications occurring during the hospital stay and charges
      generated during each time interval were abstracted. After consent was obtained,
      19 of 53 (36%) potential donors failed to donate: 9 of 19 (47%) expired prior to
      legal determination of brain death; 10 patients failed to progress to brain death
      and were made DNR. Of these, 9 died within 24 hr, 1 survived 16 days; 6 of the 10
      patients did not meet brain death criteria, and 4 were rejected by the OPO for
      reasons of infectious risks. There were 3.1+/-1.3 medical complications per
      patient. T1 was less than 4 hr in 16/19 (84%) potential donors and constituted a
      small percentage of the mean total hospital stay (37+/-10 hr). Charges generated
      during T1+T2 (33,997+/-25,843) and specifically during T2 (17,385+/-9453) were
      considerable. These charges were passed on to patients' families or third party
      payers though care was directed solely at organ procurement after diagnosis of
      lethality. We conclude that multiple medical complications are encountered in the
      care of potential organ donors; total hospital stays are short but expensive;
      more than 50% of charges generated during the total hospital stay arise from care
      provided after determination of lethality; and the goodwill of families to
      consent to organ donations of their loved ones appears to carry potential for
      significant financial burden.

PMID- 8990373
TI  - The kidneys that nobody wanted: support for the utilization of expanded criteria
      donors.
AB  - The continuing shortage of cadaveric donors necessitates constant reappraisal of
      donor refusal criteria. From 1/1/95 to 3/20/96, 180 renal transplants were
      performed at our center. Of these, 26 were kidney/pancreas, 30 pediatric, 37 live
      donor adult, and 87 adult cadaveric renal transplants (CRT). In the CRT group
      there were 31 recipients of kidneys that all other local transplant centers
      declined. We retrospectively compared this group of kidneys that nobody wanted
      (KNW) to the remaining 56 CRTs (controls) performed at our center during the same
      period. Of the 31 recipients of KNW, 18 received kidneys declined for reasons of
      advanced age, defined as > or =60 years (including 8 who also had a history of
      hypertension, 4 who also had >10% sclerosed glomeruli on biopsy, and 3 also
      declined based upon donor quality because of acute injury), 8 for donor quality
      alone (e.g., prolonged hypotension), 3 on the basis of biopsy results alone, and
      2 for anatomic abnormalities. Twelve recipients of KNW were "dual transplanted"
      with both donor kidneys. Of 27 donor variables compared between the KNW and
      control groups, only donor age (52+/-17 versus 40+/-17 years, respectively) and
      lowest total 4-hr urine output (327+/-208 versus 507+/-437 cc, respectively)
      proved to be significantly different (p< or =0.05). Of the 25 recipient variables
      examined, a significant difference was found only in serum creatinine at one
      month posttransplant (2.6+/-1.8 versus 1.8+/-1.0 mg/dl, respectively), although
      there was no difference in serum creatinine at three and six months. Actuarial
      one year patient (100 vs. 95%) and graft (97 vs. 91%) survival, KNW vs. controls
      respectively, are excellent to date. Further analyses showed no differences in
      outcome variables between recipients of KNW versus controls when the donor age
      was > or =60 years. Similar outcome was achieved by transplanting both kidneys
      from a KNW donor into a single recipient as compared with single-kidney
      transplantation from control donors. Careful donor-recipient pairing using
      kidneys from advanced-age donors for smaller, advanced-age recipients provided
      good short-term outcome. In conclusion, there was no significant difference in
      short-term outcome in recipients of KNW versus controls despite differences in
      donor age and lowest total 4-hr urine output. We believe that, with careful
      consideration, existing donor selection criteria can be expanded to include
      certain donors previously considered unusable.

PMID- 8990374
TI  - The impact of acute rejection on the development of intimal hyperplasia
      associated with chronic rejection.
AB  - The rat aortic model of chronic rejection was used to study the effect of acute
      rejection on the development of intimal hyperplasia (IH). Two model systems were
      studied. In the first, continuous monotherapy with mycophenolate mofetil (MM) (40
      mg/dx14 d followed by 30 mg/kg/d) was initiated 2 or 4 weeks posttransplant.
      Digital computer image analysis was used to quantify IH. While the development of
      IH was delayed, it was not prevented. In allografts where MM treatment was
      delayed for 2 wk, a 35.5% reduction in the amount of IH was observed. Delaying
      drug treatment for 4 wk resulted in a 42.2% reduction of IH. In contrast,
      continuous therapy from the time of transplant resulted in a 76.3% reduction in
      the amount of IH in comparison with untreated allograft controls. To further
      define the role of acute rejection in the development of IH, aortic allografts,
      ACI or (ACIxLewis)F1 (F1), were orthotopically transplanted to Lewis recipients
      and then retransplanted to donor strain secondary recipients after 2 or 4 wk.
      Grafts were harvested at 12 weeks posttransplant. When the retransplant was
      performed at 2 wk, intimal hyperplasia was decreased by 55.9% in ACI and by 66.7%
      in F1 allografts in comparison to conventional (ACI-->Lewis) allograft controls.
      When retransplantation was delayed until 4 wk, IH was not decreased in ACI
      allografts (105.9%) and was only marginally decreased in F1 allografts (26.2%).
      Syngeneic control F1 grafts (F1-->F1-->F1) did not develop significant IH at 12
      or 20 wk when retransplanted at 2 wk (10% and 12%, respectively) or when
      retransplanted at 4 wk and harvested at 12 wk (18.6%). A common feature of IH is
      the development of medial acellularity. Unlike conventional allograft recipients
      (ACI-->Lewis; no retransplantation), F1 retransplanted grafts did not develop
      significant medial myocyte dropout. In contrast, delayed MM immunosuppressive
      therapy or retransplantation of ACI allografts at 4 weeks to ACI secondary
      recipients resulted in significant loss of medial myocytes. Our results show that
      acute rejection, which occurs during the first 4 wk posttransplant, is sufficient
      to mediate the development of IH associated with CR. However the lack of a
      continued allogenic environment slows the process.

PMID- 8990375
TI  - The role of interleukin-4 in the induction phase of allogeneic neonatal
      tolerance.
AB  - We previously reported that prolonged graft survival in neonatally tolerant mice
      was associated with enhanced Th2/Th1 cytokines. To determine whether Th2 CD4
      cells function in tolerance, we examined whether we could prevent tolerance by
      blocking Th2 CD4 maturation, using anti-interleukin (IL)-4 monoclonal antibody
      treatment during neonatal antigen exposure. Anti-IL-4 treatment restored the
      ability BALB/c of mice to reject A/J skin grafts and blocked the induction of
      tolerance through multiple mechanisms. Anti-IL-4 treatment blocked the
      development of donor microchimerism and recovered the ability of mice to
      proliferate and to generate appropriate delayed-type hypersensitivity (DTH) and
      cytotoxic T lymphocyte (CTL) responses against A/J in a dose-dependent manner.
      Low-dose anti-IL-4 recovered DTH responses and interferon (IFN)-gamma production,
      but failed to completely prevent IL-4 production or to recover the CTL activity.
      No A/J-reactive IFN-gamma-producing CD8 cells were detected in these mice. In
      contrast, mice treated with higher doses of anti-IL-4 generated normal CTL
      responses against A/J, and contained A/J-reactive IFN-gamma-producing CD8 cells.
      The recovery of CTL responses and IFN-gamma-producing CD8 cells was associated
      with a more complete blocking of Th2 cytokine production. Therefore, the presence
      of IL-4 may play an important role in the induction of neonatal tolerance by
      shifting maturation of CD4 cells toward Th2 cells and away from Th1 cells, and
      also by preventing maturation of alloreactive CD8 CTL cells.

PMID- 8990376
TI  - Immunomodulatory effects of the alkaloid sinomenine in the high responder ACI-to
      Lewis cardiac allograft model.
AB  - Extracts of the plant Sinomenium acutum have been used safely since ancient times
      in Chinese medicine for treatment of rheumatic diseases, and the purified
      alkaloid, sinomenine, was recently shown to have anti-inflammatory and
      antirheumatic effects. This study describes the effects of sinomenine in the high
      responder ACI-->Lewis cardiac transplant model in which allograft rejection
      occurred at 5 days posttransplant. Treatment with sinomenine (15-30 mg/kg/day
      i.p.) or a subtherapeutic dose of cyclosporine (CsA, 1.5 mg/kg/day, i.m.)
      prolonged allograft survival only marginally (mean survival of 5.4 and 7.8 days,
      respectively). In contrast, the combination of sinomenine and CsA had a
      statistically significant synergistic effect, with a mean survival of 42.2 days
      (P < 0.001). Allografts harvested at day 5 from recipients treated with either
      sinomenine or CsA showed dense mononuclear cell infiltrates with widespread
      subepicardial infarcts, edema, and microvascular platelet and fibrin deposition.
      Immunohistologic analysis showed that intragraft leukocytes consisted of >75%
      macrophages with approximately 10-20% T cells and <5% B or NK cells. Mononuclear
      cell activation was shown by expression of IL-2R (CD25, 10-20%) and labeling for
      IL-2 (approximately 10%), and IFN-gamma (10-20%), as well as TNF-alpha (>50%) and
      iNOS (>50%), but only low levels of IL-4 or IL-10 (<5%). Intragraft endothelial
      cells were activated, as shown by upregulation of MHC class II antigen and ICAM-1
      (CD54) compared with only basal levels in normal donors hearts. Combined
      sinomenine/CsA therapy significantly enhanced graft morphology, resulting in only
      mild mononuclear cell infiltration, and an absence of infarcts, platelets, or
      fibrin deposition. Though residual intragraft mononuclear cells at day 5, as in
      control grafts, consisted primarily of macrophages plus small numbers of IL-2R+ T
      cells, these cells lacked expression of IL-2, had only low levels of IFN-gamma,
      but showed dense labeling for IL-4 and IL-10. In addition, TNF-alpha and iNOS
      were reduced to basal levels and no endothelial cell activation was observed,
      despite high titers of endothelium-bound IgM, IgG, and C3. Mitogen-induced in
      vitro proliferation of rat thymocytes was also more effectively decreased by the
      sinomenine/CsA combination than by either agent alone. These studies demonstrate
      the therapeutic value of sinomenine in transplantation, and indicate that this
      agent has novel and interesting antimacrophage, T cell, and endothelial effects
      that warrant further evaluation.

PMID- 8990377
TI  - Molecular executors of cell death--differential intrarenal expression of Fas
      ligand, Fas, granzyme B, and perforin during acute and/or chronic rejection of
      human renal allografts.
AB  - Two distinct cytolytic pathways have been characterized: one in which the
      interaction between the Fas antigen and its ligand results in apoptosis, and
      another in which the pore forming protein perforin and the serine protease
      granzyme B contribute to DNA fragmentation and cell death. We investigated
      intrarenal expression of these molecular executors of cell death in light of the
      potential participation of cytolytically active cellular elements in the
      antiallograft repertory. Reverse transcriptase-polymerase chain reaction was used
      to identify intrarenal expression of Fas antigen, Fas ligand, granzyme B and
      perforin in eighty human renal allograft biopsies; mRNA display was correlated
      with the Banff histological diagnosis of renal allografts. Our studies
      demonstrate that: (1) intrarenal expression of Fas ligand mRNA and of granzyme B
      mRNA are correlates of acute but not chronic rejection; (2) Fas ligand mRNA is
      not detectable in allografts in the absence of rejection; (3) intrarenal
      coexpression of members of each lytic pathway (Fas ligand and Fas, granzyme B,
      and perforin) and that of both pathways (e.g., Fas ligand and granzyme B) are
      correlates of acute rejection; and (4) a direct correlation exists between the
      histological severity of acute rejection and intrarenal coexpression of mRNA
      encoding Fas ligand, Fas, granzyme B, and perforin. Our studies identify, for the
      first time, the differential expression of the two major lytic pathways in acute
      and chronic allograft rejection and suggest that specific therapy directed at the
      cytotoxic attack molecules might be efficacious in the prevention and/or
      treatment of acute rejection.

PMID- 8990378
TI  - Cationic lipid-mediated transfer of the hIL-10 gene prolongs survival of
      allogeneic hepatocytes in Nagase analbuminemic rats.
AB  - Gene transfer techniques can be used as a drug delivery system to achieve local
      immunosuppression. We performed a series of experiments to identify the cationic
      lipid that most efficiently transfects isolated, cultured, rat hepatocytes; to
      optimize conditions for efficient transfection; to determine the duration of gene
      expression in vitro; and finally, to determine the survival of allogeneic
      hepatocytes transplanted into Nagase rats. Our results suggest that DOTAP is the
      best cationic lipid for transfection of cultured rat hepatocytes. In addition,
      the following conditions appear to optimize transfection efficiency: a DNA:DOTAP
      ratio of 1:6; a 24 exposure time of the hepatocytes to the DNA-DOTAP complex; a
      DNA dose of 4 microg/35 mm culture plate seeded with 2.5x10(5) rat hepatocytes.
      When transfected as described above, cultured hepatocytes expressed the hIL-10
      gene for approximately 14 days. Accordingly, Nagase rats transplanted with
      4x10(7) DOTAP-hIL-10 transfected, allogeneic hepatocytes had an abrupt rise in
      serum albumin levels that peaked within 7 days of the transplant, decreased
      abruptly after 15 days, and approached baseline by day 40. In contrast, control
      animals had a smaller albumin peak that returned to baseline within 10 days
      (P<0.01). In all animals, serum hIL-10 levels were undetectable when tested. We
      conclude that DOTAP is the best cationic lipid for transfection of cultured rat
      hepatocytes. Furthermore, hIL-10 transfected hepatocytes have a prolonged
      survival in an allogeneic host which is probably limited by loss of gene
      expression. Further studies using other vectors capable of prolonged gene
      expression will help determine if indefinite hIL-10 gene expression leads to
      indefinite graft survival.

PMID- 8990379
TI  - Nitric oxide production by mouse bone marrow-derived dendritic cells:
      implications for the regulation of allogeneic T cell responses.
AB  - Dendritic cells (DC) are the most potent known antigen presenting cells, and play
      important roles both in immunity and tolerance induction. Nitric oxide (NO) is an
      important effector molecule that is involved in numerous aspects of the immune
      response. There have been no accounts to date of efforts to determine NO
      generation by well-characterized DC. In this report we describe the production of
      NO by highly purified DEC 205+ DC propagated from mouse bone marrow in response
      to granulocyte/macrophage-colony stimulating factor (GM-CSF) + interleukin-4 (IL
      4). NO synthesis was induced in DC by interferon-gamma (IFN-gamma) and
      lipopolysaccharide (LPS), and was blocked by the inhibitor of nitric oxide
      synthase (NOS), NG-monomethyl-L-arginine (NMMA). Both "mature" B7-2+ (CD86+) DC
      and B7-2- (CD86-) DC progenitors could be induced to release NO. NO was also
      recovered from the supernatants of primary mixed leukocyte cultures containing
      comparatively high concentrations of B7-2+ DC in relation to purified allogeneic
      T cells. Furthermore, inhibition of NO release in these cultures by NMMA resulted
      in an increase in T cell proliferation. These observations suggest that NO may be
      an important soluble mediator of the interaction between DC and activated T
      cells. In addition to its ability to inhibit T cell proliferation, NO was also
      shown to induce programmed cell death in DC. This was visualized by the detection
      of DNA strand breaks with in situ nick translation. The percentage of DC
      apoptosis correlated with the level of NO in the cultures. Apoptosis was
      inhibited by the addition of NMMA. These results indicate that DC have the
      capacity both to stimulate and potentially limit the same allogeneic T cell
      response, in accordance with their production of NO.

PMID- 8990380
TI  - Acquired systemic tolerance to rat cardiac allografts induced by intrathymic
      inoculation of synthetic polymorphic MHC class I allopeptides.
AB  - This study extends the finding that intrathymic (IT) injection of 3M KC1 extracts
      of T cells induces transplant tolerance to the use of well defined polymorphic
      MHC class I allopeptides derived from the hypervariable domain of RT1.Au (WF MHC
      class I). While three of the six synthetic RT1.Au peptides were immunogenic,
      three others were nonimmunogenic when tested in ACI responders. In our initial
      studies, we examined the effects of IT injection of a mixture of equal
      concentrations of the three nonimmunogenic RT1.Au peptides on WF cardiac
      allograft survival in ACI recipients. The results showed that a single IT
      injection of 100 and 300 microg class I MHC allopeptides on day -7 relative to
      cardiac transplant did not significantly prolong graft survival in naive ACI
      recipients (MST of 9.8, and 12.3 days vs. 10.5 days in controls). In contrast,
      600 microg allopeptides injected IT resulted in modest prolongation of graft to
      an MST of 19.5 days. However, IT injection of 600 microg allopeptides combined
      with 0.5 ml ALS on day -7 led to permanent acceptance (>200 days) of cardiac
      allografts in 7/9 ACI recipients compared with survival of 24.2 days in ALS alone
      treated controls. In contrast, similar treatment led to acute rejection of third
      party (Lewis) cardiac allografts. Intravenous injection of 600 microg
      allopeptides combined with ALS did not result in prolonged graft survival (26.8
      days). The long-term unresponsive ACI recipients (>100 days) challenged with
      second-set cardiac grafts accepted permanently donor-type (WF) grafts while
      rejecting the third party (Lewis) grafts, a finding that confirms acquired
      systemic tolerance. These findings confirm the role of IT injection of synthetic
      polymorphic allopeptides in the induction of acquired thymic tolerance and
      provide the rationale for testing this strategy in large animals and eventually
      in man.

PMID- 8990381
TI  - Differential sensitivity of resting and IL-2 activated NK cells to R-verapamil.
AB  - Natural killer (NK) cells are the first lymphoid population to reconstitute the
      peripheral blood compartment of immunologically compromised bone marrow
      transplant (BMT) recipients. Recent data suggest that, among patients
      transplanted for leukemia, NK cells can prevent or delay disease relapse by
      mediating a cytotoxic graft vs leukemia (GvL) response. Although the major
      mechanism by which NK cells mediate target cell lysis involves degranulation and
      release of cytolytic effector molecules (granzymes, proteoglycans, perforin),
      accumulating evidence suggests that NK cells possess additional pathways to
      mediate target cell killing. In fact, it is well recognized that recombinant
      cytokines such as IL-2 enhance the in vitro cytolytic activity of NK cells. In
      this study, we observed that the lytic activity mediated by resting and IL-2
      activated NK cells against the same target cell appears to occur via two distinct
      pathways, as distinguished by their differential response to R-verapamil.
      Specifically, we observed that 25 microM R-verapamil inhibited the lytic activity
      of resting NK cells against K562 targets by approximately 50%. However, the lytic
      activity of IL-2 activated NK cells was unaffected by this concentration of R
      verapamil. Additional studies suggested that the inhibitory effect of R-verapamil
      on NK cytotoxic activity was associated with its ability to prevent degranulation
      of cytotoxic granules. Specifically, R-verapamil inhibited BLT esterase release
      from resting but not IL-2 activated NK cells. These data suggest that IL-2
      activated NK cells can promote target cell lysis by a pathway (possibly
      degranulation independent) distinct from that used by resting NK cells. We
      speculate that the target of R-verapamil on resting NK cells is P-glycoprotein
      (Pgp), an ABC transporter that we recently reported was expressed on NK cells and
      whose functional activity is known to be inhibited by R-verapamil.

PMID- 8990382
TI  - The unique role of interferon-gamma in the regulation of MHC expression on
      arterial endothelium.
AB  - We examined the expression of MHC class I and II in the arterial endothelium of
      interferon-gamma (IFN-gamma, GKO) and IFN-gamma-R (IFN-gamma-R, GRKO) gene
      knockout mice in comparison with mice with intact IFN-gamma and IFN-gamma-R
      genes, BALB/c and 129Sv/J wild-type, respectively. The GKO and GRKO were produced
      by gene targeting. MHC class I and II expression was assessed by mAb binding to
      frozen tissue (kidney, spleen, heart, liver) sections by immunoperoxidase
      staining in the basal state and after various stimuli: allogeneic cells,
      oxazolone skin sensitization, LPS, and rIFN-gamma. As controls, we also examined
      the expression of two other IFN-gamma inducible genes present in the endothelium,
      Ly-6 and ICAM-1. We found that basal class I expression was present in the small
      arteries and arterioles of BALB/c and 129Sv/J wild-type mice but absent from
      arterial endothelium of GKO and GRKO mice. Class I was induced in the endothelium
      of BALB/c and 129Sv/J wild-type mice by three in vivo stimuli: allogeneic, LPS,
      and oxazolone, whereas class II was only induced after allogeneic stimulus.
      Administration of rIFN-gamma induced class I in the endothelium of GKO and BALB/c
      wild-type mice. The basal expression of Ly-6 and ICAM-1 was similar in the
      arteries of GKO and BALB/c wild-type mice, indicating that, the basal expression
      of these proteins in endothelium is IFN-gamma independent, unlike class I. In
      summary, basal class I expression in arterial endothelium is not constitutive as
      previously believed, but is dependent on basal IFN-gamma production. IFN-gamma
      has an essential role in the induction of class I and II expression in arterial
      endothelium. The fact that MHC class I is induced in endothelium may be useful
      therapeutically for reduction of immune recognition in transplantation.

PMID- 8990383
TI  - The induction of class I and II major histocompatibility complex by allogeneic
      stimulation is dependent on the transcription factor interferon regulatory factor
      1 (IRF-1): observations in IRF-1 knockout mice.
AB  - Hosts undergoing allograft rejection show increased MHC expression locally in the
      graft and systemically in the normal host organs, mediated principally by IFN
      gamma. The transcription factor IRF-1 has been implicated in the regulation of
      MHC expression by IFNs in vitro as well as in the regulation of production of
      some cytokines. We investigated the role of IRF-1 in vivo in the systemic
      regulation of MHC expression in hosts undergoing rejection of allogeneic tumors
      by comparing MHC induction in mice with normal IRF-1 genes (wild type or WT mice)
      with mice with disrupted IRF-1 genes (IRF-1 knockout or IRF-1 KO mice). We
      assessed MHC product expression by immunohistology and by radiolabeled antibody
      binding to tissue homogenates, and MHC mRNA levels by Northern blotting. By
      immunohistology in mice undergoing allogeneic stimulation by the ascites tumor
      cells, kidneys of WT mice showed massive class I and II induction, but kidneys
      from IRF-1 KO mice showed almost no class I and II induction. Allograft rejection
      also increased class I and II product levels by radiolabeled antibody binding and
      steady state mRNA levels, but again IRF-1 KO mice showed severe impairment of MHC
      induction. Similar impaired MHC class I and II induction was seen in heart and
      spleen, but in liver the IRF-1 mice showed impaired class I induction but
      unimpaired class II induction. The results indicate that IRF-1 has an essential
      role in both class I and class II MHC induction in allogeneic responses, but that
      a component of IRF-1 independent MHC induction is also demonstrable in some
      tissues. The reduction in MHC induction by allogeneic stimulation probably
      reflects decreased response to IFN-gamma and other cytokines as well as some
      reduction in the amount of cytokines produced.

PMID- 8990384
TI  - Evidence for the in vivo role of class II transactivator in basal and IFN-gamma
      induced class II expression in mouse tissue.
AB  - The class II transactivator (CIITA) is a protein that induces the transcription
      of MHC class II genes. We studied the expression of CIITA in vivo, comparing
      steady state levels of CIITA and class II mRNA in various mouse tissues. Many
      tissues in normal mice contained mRNA for CIITA, correlating with class II mRNA.
      The basal expression of CIITA and class II mRNA in mice with disrupted IFN-gamma
      genes (GKO mice) was similar to that in wild-type mice. Injection of rIFN-gamma
      strongly induced CIITA and class II mRNA: CIITA mRNA increased at 2 hr and
      declined to baseline by 48 hr, whereas class II mRNA increased at 24 hr and
      returned to baseline at 7 days. Proinflammatory stimuli that induce IFN-gamma
      production (allogeneic cells and LPS) induce CIITA and class II expression in
      wild-type mice, but not in GKO mice. CIITA induction by IFN-gamma was partially
      sensitive to cycloheximide, suggesting that another protein is required for CIITA
      induction. The data suggest that CIITA is a major regulator of basal and induced
      class II expression in vivo.

PMID- 8990385
TI  - Acute rejection of vascularized heart allografts in the absence of IFNgamma.
AB  - It is generally assumed that IFNgamma plays a central role in acute allograft
      rejection. To test this hypothesis, we transplanted fully allogeneic (MHC class I
      and II incompatible) C3H/HeJ (H2k) murine hearts to IFNgamma-/- (IFNgamma gene
      knockout) and IFNgamma+/+ BALB/c (H2d) mice. The phenotype of IFNgamma-/- mice
      was confirmed by demonstrating absent IFNgamma protein production by Con A
      stimulated IFNgamma-/- splenocytes. Both IFNgamma-/- and IFNgamma+/+ strains
      rejected transplanted hearts acutely: graft survival (mean +/- SD) was 5.2+/-0.4
      and 6.0+/-0.0 days, respectively. Histologic examination revealed similar
      patterns of acute cellular rejection in both mouse groups. IFNgamma mRNA was
      present in hearts rejected by IFNgamma+/+ mice but was absent in those rejected
      by IFNgamma-/- mice. IL-2, IL-4, IL-10, and TNFalpha mRNA expression, on the
      other hand, was similar in grafts rejected by either strain. We also observed
      that hapten-induced delayed-type hypersensitivity (DTH) response was
      significantly reduced but not absent in IFNgamma-/- mice. Our results demonstrate
      that IFNgamma is not required for acute cellular rejection of fully allogeneic
      murine hearts. We propose that non-DTH mechanisms of allograft destruction could
      be enhanced in the absence of IFNgamma and thus lead to robust acute rejection.

PMID- 8990386
TI  - The role of the perforin and Fas pathways of cytotoxicity in skin graft
      rejection.
AB  - Cell-mediated cytotoxicity is believed to play an important role in the
      mechanisms of rejection following organ and tissue transplantation. We have
      investigated the role of the perforin and Fas pathways of cell-mediated
      cytotoxicity on the survival of xenogeneic, allogeneic and hemiallogeneic skin
      grafts. Wild type C57BL/6 (B6), perforin deficient C57BL/6 (B6 PKO) and Fas
      ligand deficient (B6 gld/gld) mice were grafted with xenogeneic Lewis rat skin
      grafts, or allogeneic B10.BR, class I disparate B6 bml, class II disparate B6
      bm12, and Fas deficient allogeneic C3H lpr/lpr grafts. No significant difference
      was observed in the timing of rejection with B6 PKO mice as recipients when
      compared with normal B6 controls. All grafts were also rejected by B6 gld/gld
      recipients, but with a significantly delayed pattern of rejection, showing,
      therefore, that Fas, although not critical, may participate to the mechanisms of
      rejection. Neither perforin nor Fas, however, seem to be essential for rejection
      of a skin graft, and it is likely that alternative mechanisms assume an important
      role in the effector phase of rejection once these cell-cytotoxic pathways are
      abrogated.

PMID- 8990387
TI  - Cyclosporine protects glomeruli from FSGS factor via an increase in glomerular
      cAMP.
AB  - Cyclosporine (CsA) administration to patients with recurrent focal segmental
      glomerulosclerosis (FSGS) after transplantation results in remission of
      proteinuria. We have shown that sera from patients with recurrent FSGS can
      increase the glomerular albumin permeability (Palbumin) and that increase in
      glomerular cAMP levels can alter the permeability characteristics of glomeruli in
      vitro. The purpose of this study was to determine if the increased glomerular
      levels of cAMP were related to the protective effects of CsA on an increase in
      Palbumin by FSGS sera. Glomeruli from Sprague-Dawley rats following
      intraperitoneal administration of CsA (25 mg/kg/day), cremophore (25 mg/kg/day),
      or saline for 5 days were incubated with 1:50 dilution of serum from three FSGS
      patients or with pooled normal human serum prior to calculation of Palbumin.
      Glomerular cAMP was measured by radioimmunoassay. Glomerular ultrastructural
      changes were assessed by transmission electron microscopy (TEM). Serum from three
      FSGS patients markedly increased Palbumin of glomeruli from saline or cremophore
      treated rats (saline, 0.68+/-0.08; 0.72+/-0.07; 0.70+/-0.07; and cremophore,
      0.79+/-0.05; 0.81+/-0.02; 0.79+/-0.01; n=25 glomeruli in each group). In contrast
      Palbumin of glomeruli from CsA treated rats was not increased by any of the three
      FSGS sera tested (0.03+/-0.02; 0.04+/-0.05; 0.02+/-0.07, n=25 glomeruli in each
      group). Glomerular cAMP (pmol/mg of protein) increased 5 fold in CsA treated rats
      (328+/-26; 5 rats) compared with cremophore or saline treated rats (87+/-24 and
      65+/-23, P<0.01; 5 rats in each group). The glomerular basement membrane appeared
      to be thickened and the lamina densa had an irregular appearance after treatment
      with CsA. No ultrastructural changes of glomerular epithelial or endothelial
      cells were evident. We conclude that CsA may have a direct protective effect on
      the glomerular filtration barrier in FSGS. We postulate that increased levels of
      glomerular cAMP by CsA may play an important role in protecting the glomerular
      Palbumin effect of the FSGS factor and may contribute to remission of proteinuria
      in FSGS patients.

PMID- 8990388
TI  - T cell independence of macrophage and natural killer cell infiltration, cytokine
      production, and endothelial activation during delayed xenograft rejection.
AB  - Rejection of guinea pig cardiac grafts in rats depleted of complement takes place
      in 3-4 days and involves progressive mononuclear cell infiltration and cytokine
      expression, fibrin and antibody deposition, and endothelial cell up-regulation of
      adhesion and procoagulant molecules, a process termed delayed xenograft rejection
      (DXR). The relative contribution of each effector mechanism and the role of T
      cells in this complex process are unknown, although small numbers of interleukin
      (IL) 2 receptor-positive T cells are present at the time of rejection. We
      investigated the importance of T cells in DXR by comparing discordant xenograft
      responses of nude rats, which lack T cell receptor (TCR)-alpha/beta+ cells, with
      those of normal Lewis rats. Nude or Lewis rats receiving guinea pig cardiac
      grafts were assigned to one of three groups: no therapy, daily administration of
      cobra venom factor (CVF), or splenectomy plus daily CVF. All untreated rats
      rejected their xenografts within 10-15 min, whereas grafts in complement-depleted
      recipients survived a further 3-4 days; splenectomy had no significant additional
      effect upon graft survival. Immunohistologic analysis in CVF-treated nude
      recipients with or without splenectomy showed: (1) considerable leukocyte
      infiltration of xenografts (mean +/- SD, 76+/-14 and 71+/-16 leukocytes/field,
      respectively, at 72 hr, compared with 68+/-17 in Lewis rats), consisting largely
      of macrophages (>75% of total leukocytes) plus small numbers of natural killer
      cells (10-20%) with no detectable B or T cells (TCR-alpha/beta or TCR
      gamma/delta); (2) at least 10-fold lower levels of intragraft IgM or IgG
      deposition than in corresponding Lewis recipients; and (3) considerable cytokine
      expression by intragraft macrophages (IL-12, tumor necrosis factor-alpha,
      monocyte chemoattractant protein-1, IL-1beta, IL-6, IL-7, IL-12) and natural
      killer cells (interferon-gamma), as well as up-regulation of tissue factor
      expression and dense fibrin deposition. Analysis of recipient sera of both
      control and nude rats by ELISA, for the binding of IgG or IgM to guinea pig
      platelets, showed a rapid rise after transplantation in the titers of IgM and IgG
      antibodies, which was abrogated by prior splenectomy; i.e., data from
      splenectomized xenograft recipients reflect the presence of only basal levels of
      IgM and IgG. Thus, our data in nude rats show rejection times and intragraft
      features of DXR comparable to those in immunocompetent Lewis recipients, despite
      a lack of detectable host T cells, and, in the case of splenectomized rats, only
      about one tenth of normal xenoreactive antibody levels. Our data document a new
      model in which to analyze the immunopathogenesis of DXR.

PMID- 8990389
TI  - Circulating human mononuclear cells exhibit augmented lysis of pig endothelium
      after activation with interleukin 2.
AB  - In immunohistochemical studies investigating the cellular infiltrates in pig
      xenografts undergoing delayed rejection by newborn and adult primate recipients,
      we observed extensive infiltration with primate macrophages and natural killer
      (NK) cells. To extend these studies in vitro, we investigated the functional
      properties of human NK cell precursors with respect to their potential
      interactions with pig aortic endothelial cells (PAEC). Using a short-term 51Cr
      release assay, human peripheral blood mononuclear cells (PBMC) demonstrated
      spontaneous and interleukin (IL) 2 augmented lytic activity against PAEC which
      increased with increasing effector to target cell ratio. Treatment of human PBMC
      with anti-CD2 significantly reduced this NK lytic activity by IL-2-activated
      PBMC. Finally, we investigated the effects of PAEC treatment with certain
      macrophage-derived human cytokines on adhesion of IL-2-activated human PBMC.
      Treatment of PAEC with IL-1 and tumor necrosis factor-alpha, in a dose-dependent
      manner, increased adherence of IL-2-activated human PBMC. These results
      demonstrate that humans contain circulating NK cells capable of lysing PAEC after
      activation with IL-2, that the mechanism involves interactions between CD2 and
      its ligand on porcine endothelium, and that these interactions may be influenced
      by macrophage-derived cytokines produced at the site of xenograft rejection.

PMID- 8990390
TI  - Pregnancy after donor nephrectomy.
AB  - Potential female donors frequently ask whether unilateral nephrectomy will impair
      future childbearing capabilities. To address this question, we surveyed 220 women
      who underwent donor nephrectomy between 1985 and 1992. Of the 144 women who
      responded, 33 became pregnant after donation for a total of 45 pregnancies.
      Seventy-five percent of the pregnancies were carried to term without difficulty.
      Complications incurred during gestation included miscarriage (13.3%),
      preeclampsia (4.4%), gestational hypertension (4.4%), proteinuria (4.4%), and
      tubal pregnancy (2.2%). Four of the 45 pregnancies (excluding miscarriages)
      required preterm hospitalization, resulting in an overall morbidity of 8.8%.
      There were no pregnancy-related deaths, and no fetal abnormalities were reported.
      Problems with persistent hypertension, proteinuria, or changes in renal function
      were not noted. None of the above complications exceeded what has been noted for
      the general population. Infertility was a problem in 8.3% (3/36) of our
      respondents, compared with a worldwide incidence of 16.7%. Based on these
      results, we conclude that donor nephrectomy is not detrimental to the prenatal
      course or outcome of future pregnancies.

PMID- 8990391
TI  - Decreased urinary excretion of nitric oxide in acute rejection episodes in
      pediatric renal allograft recipients.
AB  - Acute renal allograft rejection continues to have a negative effect on graft
      survival despite a better understanding of the molecular basis of renal allograft
      rejection. Nitric oxide (NO) has important biological functions in cell defense
      and injury and some evidence exists that it may act as an immunomodulator in
      allograft transplantation. To determine if NO has any role in acute renal
      allograft rejection in pediatric patients, acute rejection episodes in pediatric
      renal transplant recipients were evaluated. Four out of eleven patients who
      received a renal allograft in 1995 at Children's Kidney Center at The Children's
      Hospital of Buffalo had eight episodes of acute rejection. One patient received a
      living-related and three received cadaveric grafts. Stable metabolites of NO (NO
      2 + NO-3 = NOx) were measured in the serum and urine samples of the patients
      daily. Serum levels of NO did not change significantly during acute rejection
      episodes. Urinary NOx levels decreased by 73+/-9% of the baseline values during
      episodes of acute rejection: mean +/-SE urinary nitric oxide/creatinine ratio
      (NOx/Cr) of 0.17+/-0.05 at baseline vs. 0.05+/-0.01 during rejection (P=0.02).
      Successful treatment of acute rejection by administration of high dose i.v.
      steroids or OKT-3 induced acute rises in the urinary NO levels to baseline
      values: NO/Cr = 0.17+/-0.04 (mean +/-SE). We conclude that urinary NO excretion
      decreases significantly during acute renal allograft rejection and that NOx
      concentration in the urine increases in response to successful antirejection
      therapy.

PMID- 8990392
TI  - Inability of serum myocyte death markers to predict acute cardiac allograft
      rejection.
AB  - Acute cardiac rejection involves myocyte necrosis. Hence, markers of myocyte
      death may be useful in diagnosing rejection. Creatine kinase MB, MB isoforms, and
      troponins I and T were measured in 186 patients undergoing 365 endomyocardial
      biopsies. No differences were noted with rejection (rejectors vs. nonrejectors:
      CK=63.8 U/L and 86.6 U/L, P=0.0881; CK MB=2.04 ng/ml and 2.06 ng/ml, P=0.949;
      troponin T=0.134 ng/ml and 0.0881 ng/ml, P=0.374; troponin I=0.216 ng/ml and
      0.707 ng/ml, P=0.357). The time course of troponins T and I levels in rejectors
      and nonrejectors do not differ with both groups having early elevations. Markers
      of myocyte death are inadequate predictors of acute rejection in cardiac
      allografts. The time course of troponins T and I suggests a possible role as
      prognostic indicators of outcome.

PMID- 8990393
TI  - CD28-B7 T cell costimulatory blockade by CTLA4Ig in the rat renal allograft
      model: inhibition of cell-mediated and humoral immune responses in vivo.
AB  - Blocking CD28-B7 T-cell costimulation by CTLA4Ig induces tolerance to rat renal
      allografts and inhibits Th1, but spares Th2, cytokines. We now report on the
      mechanisms of CD28-B7 blockade in this model. Lymphocytes from CTLA4Ig-treated
      animals showed significant reduction of mixed lymphocyte response, as well as
      antidonor cytotoxic T-cell effector function, as compared with rejecting
      controls. Flow cytometry studies on sera of renal allograft recipients showed
      complete inhibition of antidonor humoral responses by CTLA4Ig. Analysis by
      reverse transcriptase-polymerase chain reaction and immunohistology showed that
      intragraft macrophage products, monocyte chemoattractant protein-1 and inducible
      nitric oxide synthase, were reduced by CTLA4Ig therapy. Immunohistologic studies
      also showed reduced intragraft macrophage infiltration and decreased staining for
      the fibrogenic and mitogenic growth factor, transforming growth factor-beta.
      These results indicate that CD28-B7 blockade inhibits cell-mediated and humoral
      immune responses, and suggest that strategies targeting T-cell costimulation may
      provide a novel approach to prevent chronic allograft rejection.

PMID- 8990394
TI  - Secondary structure model of the RNA recognized by the reverse transcriptase from
      the R2 retrotransposable element.
AB  - RNA transcripts corresponding to the 250-nt 3' untranslated region of the R2 non
      LTR retrotransposable element are recognized by the R2 reverse transcriptase and
      are sufficient to serve as templates in the target DNA-primed reverse
      transcription (TPRT) reaction. The R2 protein encoded by the Bombyx mori R2 can
      recognize this region from both the B. mori and Drosophila melanogaster R2
      elements even though these regions show little nucleotide sequence identity. A
      model for the RNA secondary structure of the 3' untranslated region of the D.
      melanogaster R2 retrotransposon was developed by sequence comparison of 10
      species aided by free energy minimization. Chemical modification experiments are
      consistent with this prediction. A secondary structure model for the 3'
      untranslated region of R2 RNA from the R2 element from B. mori was obtained by a
      combination of chemical modification data and free energy minimization. These two
      secondary structure models, found independently, share several common sites. This
      study shows the utility of combining free energy minimization, sequence
      comparison, and chemical modification to model an RNA secondary structure.

PMID- 8990395
TI  - Identification of specific nucleotide sequences and structural elements required
      for intronic U14 snoRNA processing.
AB  - Vertebrate U14 snoRNAs are encoded within hsc70 pre-mRNA introns and U14
      biosynthesis occurs via an intron-processing pathway. We have shown previously
      that essential processing signals are located in the termini of the mature U14
      molecule and replacement of included boxes C or D with oligo C disrupts snoRNA
      synthesis. The experiments detailed here now define the specific nucleotide
      sequences and structures of the U14 termini that are essential for intronic
      snoRNA processing. Mutagenesis studies demonstrated that a 5', 3'-terminal stem
      of at least three contiguous base pairs is required. A specific helix sequence is
      not necessary and this stem may be extended to as many as 15 base pairs without
      affecting U14 processing. The spatial positioning of boxes C and D with respect
      to the terminal stem is also important. Detailed analysis of boxes C and D
      revealed that both consensus sequences possess essential nucleotides. Some, but
      not all, of these critical nucleotides correspond to those required for the
      stable accumulation of nonintronic yeast U14 snoRNA. The presence of box C and D
      consensus sequences flanking a terminal stem in many snoRNA species indicates the
      importance of this "terminal core motif" for snoRNA processing.

PMID- 8990396
TI  - RNA-dependent RNA polymerase activity associated with the yeast viral p91/20S RNA
      ribonucleoprotein complex.
AB  - 20S RNA is a noninfectious viral single-stranded RNA found in most laboratory
      strains of the yeast Saccharomyces cerevisiae. 20S RNA encodes a protein of 91
      kDa (p91) that contains the common motifs found among RNA-dependent RNA
      polymerases from RNA viruses. p91 and 20S RNA are noncovalently associated in
      vivo, forming a ribonucleoprotein complex. We detected an RNA polymerase activity
      in p91/20S RNA complexes isolated by high-speed centrifugation. The activity was
      not inhibited by actinomycin D nor alpha-amanitin. The majority of the in vitro
      products was 20S RNA and the rest was the complementary strands of 20S RNA.
      Because the extracts were prepared from cells accumulating 20S RNA over its
      complementary strands, these in vitro products reflect the corresponding
      activities in vivo. When the p91/20S RNA complexes were subjected to sucrose
      gradient centrifugation, the polymerase activity cosedimented with the complexes.
      Furthermore, an RNA polymerase activity was detected in the complex by an
      antibody-linked polymerase assay using anti-p91 antiserum, suggesting that p91 is
      present in the active RNA polymerase machinery. These results together indicate
      that p91 is the RNA-dependent RNA polymerase or a subunit thereof responsible for
      20S RNA replication.

PMID- 8990397
TI  - Evidence for light/redox-regulated splicing of psbA pre-RNAs in Chlamydomonas
      chloroplasts.
AB  - Efficient splicing in vivo of most self-splicing group I introns is believed to
      require proteins, raising the possibility that splicing could be regulated;
      however, examples of such regulation have been lacking. The Chlamydomonas
      reinhardtii chloroplast psbA gene contains four large group I introns that self
      splice efficiently in vitro, but only under nonphysiological conditions. The psbA
      gene encodes the D1 protein of photosystem II, which is synthesized at very high
      rates in the light in order to replace photodamaged protein. We show that psbA
      pre-mRNAs, containing one or more introns, accumulate in wild-type cells in the
      dark, apparently due to rate-limited splicing. Analysis of the pre-RNAs indicates
      that splicing of the four introns does not follow a strict order. Exposure of
      cells to light induced rapid (15-20 min) decreases in precursor levels of
      approximately 3-5-fold (depending on the intron), which were accompanied by
      transient increases in free intron levels. Because light also stimulated psbA
      transcription approximately 2-fold over the same period, the data suggests that
      light increases the splicing efficiency of psbA introns approximately 6-10-fold.
      Similar estimates of the extent of light stimulation were obtained by analyzing
      precursor decay rates in the presence of actinomycin D. The effect of light is
      specific for psbA introns, because levels of unspliced 23S pre-RNA did not
      decrease. The light-induced increase in psbA pre-RNA processing was abolished by
      inhibitors of photosynthetic electron transport, but not by the ATP synthesis
      inhibitor, carbonylcyanide m-chlorophenylhydrazone, which actually promoted pre
      RNA processing in the dark. Finally, nonphotosynthetic mutants, including the
      tscA-lacking photosystem I mutant, H13, did not show evidence of light-stimulated
      RNA processing. However, the light response was restored in photosynthetic
      transformants of H13 that had been complemented with the tscA gene. These data
      suggest strongly that light coordinately stimulates splicing of all four psbA
      introns. Moreover, they demonstrate that this response to light is mediated by
      photosynthetic electron transport. The implications of these results for the
      regulation of psbA gene expression are discussed.

PMID- 8990398
TI  - Identification of 2'-hydroxyl groups required for interaction of a tRNA anticodon
      stem-loop region with the ribosome.
AB  - Synthetic RNA stem loops corresponding to positions 28-42 in the anticodon region
      of tRNA(Phe) bind efficiently in an mRNA-dependent manner to ribosomes, whereas
      those made from DNA do not. In order to identify the positions where ribose is
      required, the anticodon stem-loop region of tRNA(Phe) (Escherichia coli) was
      synthesized chemically using a mixture of 2'-hydroxyl- and 2'-deoxynucleotide
      phosphoramidites. Oligonucleotides whose ribose composition allowed binding were
      retained selectively on nitrocellulose filters via binding to 30S ribosomal
      subunits. The binding-competent oligonucleotides were submitted to partial
      alkaline hydrolysis to identify the positions that were enriched for ribose.
      Quantification revealed a strong preference for a 2'-hydroxyl group at position
      U33. This was shown directly by the 50-fold lower binding affinity of a stem loop
      containing a single deoxyribose at position U33. Similarly, defective binding of
      the corresponding U33-2'-O-methyl-substituted stem-loop RNA suggests that absence
      of the 2'-hydroxyl group, rather than an altered sugar pucker, is responsible.
      Stem-loop oligoribonucleotides from different tRNAs with U33-deoxy substitutions
      showed similar, although quantitatively different effects, suggesting that
      intramolecular rather than tRNA-ribosome interactions are affected. Because the
      2'-hydroxyl group of U33 was shown to be a major determinant of the U-turn of the
      anticodon loop in the crystal structure of tRNA(Phe) in yeast, our finding might
      indicate that the U-turn conformation in the anticodon loop is required and/or
      maintained when the tRNA is bound to the ribosomal P site.

PMID- 8990399
TI  - Analysis of bacteriophage N protein and peptide binding to boxB RNA using
      polyacrylamide gel coelectrophoresis (PACE).
AB  - The antitermination protein N from bacteriophage lambda (Nlambda) interacts with
      the nut site in its own mRNA, as well as host factors, to facilitate formation of
      a termination-resistant transcription complex. The conserved, amino-terminal
      arginine-rich domain of Nlambda protein is known to interact with a small RNA
      hairpin (boxB) derived from the nut site RNA. We have examined the binding of
      Nlambda protein, peptides derived from the amino terminus of Nlambda, and the
      related phage P22 N protein to lambda boxB RNAs. To facilitate the study of
      complexes that are not amenable to gel retardation assays, a new polyacrylamide
      affinity coelectrophoresis technique (PACE) was developed. Using the PACE assay,
      we have demonstrated that a 19-amino acid peptide from the amino terminus of
      Nlambda protein binds lambda boxB RNA with a Kd,app of 5.2 nM. PACE was also used
      to study the binding affinity of a number of Nlambda peptide and lambda boxB RNA
      mutants. The PACE technique is complementary to the traditional gel retardation
      assay for direct measurement of binding interactions, and will be useful for any
      procedure that requires a pool of RNAs to be resolved based on their relative
      affinities for proteins or peptides.

PMID- 8990400
TI  - The genetic stability of potato spindle tuber viroid (PSTVd) molecular variants.
AB  - RNA viruses propagate as a population of genetically related entities composing a
      quasi-species. Specific representatives are the result of both a high mutation
      rate during replication and competition between the continuously arising sequence
      variants. Similar to other RNA pathogens, potato spindle tuber viroid (PSTVd)
      propagates as a population of similar but nonidentical sequences. The sequence of
      progeny molecules derived from cloned molecular variants of PSTVd were studied
      after one and six consecutive plant passages. Although the severe parental
      sequence S23 was found to be genetically stable, all five other parental
      sequences analyzed, irrespective of their pathogenicity, led to the appearance of
      complex populations. Divergence of the progeny was observed at the sequence
      level, but also, more surprisingly, at the level of the pathogenicity of
      individual progeny molecules. In two cases, the parental sequence was retained in
      the progeny population. In the other cases, it was completely out-competed and
      eliminated, sometimes in as little as one plant passage. Although it has been
      observed previously that artificially mutated PSTVd molecules may revert rapidly
      to the wild-type sequence, this study presents direct evidence for the rapid
      evolution of naturally occurring PSTVd sequence variants.

PMID- 8990404
TI  - Molecular biology of plasminogen activators: what are the clinical implications
      of drug design?
AB  - The initial work on thrombolytic therapy for acute myocardial infarction (AMI)
      focused on intracoronary administration of streptokinase. Continuing research has
      given rise to the development of both second- and third-generation agents and
      consequent refinements in thrombolytic regimens. Intravenous recombinant tissue
      plasminogen activator (t-PA, or alteplase) proved superior to both intracoronary
      and intravenous streptokinase with regard to reperfusion efficacy and impact on
      survival. An accelerated dosage regimen was later devised to allow the
      administration of t-PA over a shorter period of time. Unfortunately, t-PA failed
      to lessen the risk of bleeding complications that had plagued the use of
      streptokinase. The wild-type t-PA molecule has since been modified in an attempt
      to achieve improved lytic characteristics with less bleeding risk. Among these
      third-generation agents is reteplase (r-PA); compared with alteplase, reteplase
      has a prolonged half-life and seems to offer more rapid thrombolysis. Promising
      results have been obtained in large, randomized trials of reteplase. Another new
      agent is the TNK mutant of t-PA, which also has a prolonged half-life and seems
      to produce more rapid and complete thrombolysis, as well as less risk of
      intracranial bleeding than with alteplase in animal models. Although large,
      randomized trials have not yet been conducted, encouraging results have emerged
      from preliminary dose-ranging trials with TNK. A third new agent, n-PA, has an
      even longer half-life and has shown improved lytic activity in animal models. A
      dose-ranging trial of n-PA is currently under way. Despite the fact that each of
      the third-generation drugs has shown considerable potential with regard to
      improving the efficacy of thrombolytic therapy, the risk of intracranial bleeding
      remains problematic and will need to be assessed in large, randomized trials.

PMID- 8990402
TI  - Probing the structure of the Escherichia coli 10Sa RNA (tmRNA).
AB  - The conformation of the Escherichia coli 10Sa RNA (tmRNA) in solution was
      investigated using chemical and enzymatic probes. Single- and double-stranded
      domains were identified by hydrolysis of tmRNA in imidazole buffer and by
      lead(II)-induced cleavages. Ribonucleases T1 and S1 were used to map unpaired
      nucleotides and ribonuclease V1 was used to identify paired bases or stacked
      nucleotides. Specific atomic positions of bases were probed with dimethylsulfate,
      a carbodiimide, and diethylpyrocarbonate. Covariations, identified by sequence
      alignment with nine other tmRNA sequences, suggest the presence of several
      tertiary interactions, including pseudoknots. Temperature-gradient gel
      electrophoresis experiments showed structural transitions of tmRNA starting
      around 40 degrees C, and enzymatic probing performed at selected temperatures
      revealed the progressive melting of several predicted interactions. Based on
      these data, a secondary structure is proposed, containing two stems, four stem
      loops, four pseudoknots, and an unstable structural domain, some connected by
      single-stranded A-rich sequence stretches. A tRNA-like domain, including an
      already reported acceptor branch, is supported by the probing data. A second
      structural domain encompasses the coding sequence, which extends from the top of
      one stem-loop to the top of another, with a 7-nt single-stranded stretch between.
      A third structural module containing pseudoknots connects and probably orients
      the tRNA-like domain and the coding sequence. Several discrepancies between the
      probing data and the phylogeny suggest that E. coli tmRNA undergoes a
      conformational change.

PMID- 8990405
TI  - How much do we gain by reducing time to reperfusion therapy?
AB  - Emphasis continues to be placed on the need to minimize the time elapsed between
      the onset of symptoms of myocardial infarction and the initiation of thrombolytic
      therapy. Numerous large-scale trials have revealed an inverse relation between
      time-to-treatment and the degree of reduction in the risk of adverse clinical
      outcomes. Still to be resolved is the question of whether additional benefit can
      be gained by treating within the first hour. Many factors that influence delays
      to presentation are also associated with a higher risk of mortality, and these
      factors vary with patient characteristics. These same factors are also associated
      with longer treatment delay and greater mortality risk. Although the greatest
      opportunity for reducing time-to-treatment lies in reducing presentation time,
      public education efforts have been largely unsuccessful. Despite the fact that
      treatment delay generally accounts for a smaller proportion of total delay time
      than does presentation delay, it may be more amenable to shortening through
      measures such as transmission of electrocardiograms from the field; emergency
      department protocols for the rapid triage, assessment, and treatment of patients
      with chest pain; training emergency department physicians to administer
      thrombolytic therapy without a cardiology consult; and storing thrombolytic
      agents in the emergency department.

PMID- 8990401
TI  - The expression cassette determines the functional activity of ribozymes in
      mammalian cells by controlling their intracellular localization.
AB  - In order to better understand the influence of RNA transcript context on RNA
      localization and catalytic RNA efficacy in vivo, we have constructed and
      characterized several expression cassettes useful for transcribing short RNAs
      with well defined 5' and 3' appended flanking sequences. These cassettes contain
      promoter sequences from the human U1 snRNA, U6 snRNA, or tRNA Meti genes, fused
      to various processing/stabilizing sequences. The levels of expression and the sub
      cellular localization of the resulting RNAs were determined and compared with
      those obtained from Pol II promoters normally linked to mRNA production, which
      include a cap and polyadenylation signal. The tRNA, Ul, and U6 transcripts were
      nuclear in localization and expressed at the highest levels, while the standard
      Pol II promoted transcripts were cytoplasmic and present at lower levels. The
      ability of these cassettes to confer ribozyme activity in vivo was tested with
      two assays. First, an SIV-growth hormone reporter gene was transiently
      transfected into human embryonic kidney cells expressing an anti-SIV ribozyme.
      Second, cultured T lymphocytes expressing an anti-HIV ribozyme were challenged
      with HIV. In both cases, we found that the ribozymes were effective only when
      expressed as capped, polyadenylated RNAs transcribed from Pol II cassettes that
      generate a cytoplasmically localized ribozyme that facilitates co-localization
      with its target. We also show that the inability of the other cassettes to
      support ribozyme-mediated inhibitory activity against their cytoplasmic target is
      very likely due to the resulting nuclear localization of these ribozymes. These
      studies demonstrate that the ribozyme expression cassette determines its
      intracellular localization and, hence, its corresponding functional activity.

PMID- 8990406
TI  - Patency trials with reteplase (r-PA): what do they tell us?
AB  - Thrombolytic therapy has been shown to reduce mortality and morbidity after acute
      myocardial infarction. Therapeutic benefit seems to be directly correlated with
      completeness of reperfusion (Thrombolysis in Myocardial Infarction [TIMI] grade 3
      flow) of the infarct-related coronary artery, as well as the timeliness of
      reperfusion. To determine which regimen of reteplase (r-PA), a deletion mutant of
      wild-type tissue plasminogen activator (t-PA), is most effective for clinical
      thrombolysis, several reteplase regimens were compared with the most successful
      standard regimens of recombinant t-PA (alteplase) in 2 large-scale, randomized
      studies. All patients received aspirin and intravenous heparin. In the Reteplase
      Angiographic Phase II International Dose Finding Trial (RAPID-1), results in 606
      randomized patients showed that a 10 + 10 U double bolus of reteplase was more
      effective than a 15 U single bolus, a 10 + 5 double bolus, or conventional
      alteplase (100 mg over 3 hours). In the Reteplase versus Alteplase Patency
      Investigation During Acute Myocardial Infarction (RAPID-2) trial, results in 324
      patients showed that significantly more patients achieved patency of the infarct
      related artery (TIMI grade 2 or 3 flow) at 90 minutes with reteplase (10 + 10 U
      double bolus) than with accelerated alteplase (100 mg over 90 minutes): 83.4%
      versus 73.3%, respectively (p = 0.03). The incidence of complete patency (TIMI
      grade 3 flow) at 90 minutes was likewise greater with reteplase than with
      accelerated alteplase (59.9% vs 45.2%, respectively; p = 0.01). At 60 minutes,
      the incidence of TIMI grade 2 or 3 flow was also significantly higher with
      reteplase than with alteplase (81.8% vs 66.1%, respectively; p = 0.01), as was
      the incidence of TIMI grade 3 flow (51.2% vs 37.4%, respectively; p < 0.031). The
      35-day mortality rate was 4.1% for reteplase and 8.4% for alteplase (p = not
      significant). Reteplase and alteplase did not differ significantly with regard to
      the occurrence of severe bleeding (12.4% vs 9.7%, respectively) or hemorrhagic
      stroke (1.2% vs 1.9%, respectively). The results of these trials show that
      reteplase, given as a 10 + 10 U double bolus, achieves significantly higher rates
      of early reperfusion of the infarct-related coronary artery and is associated
      with significantly fewer acute coronary interventions when compared with front
      loaded alteplase. The benefits of reteplase are achieved without any apparent
      increased risk of complications.

PMID- 8990407
TI  - Clinical trials in thrombolytic therapy: what do they tell us? INJECT 6-month
      outcomes data.
AB  - Numerous controlled clinical trials have documented the efficacy of thrombolytic
      agents in reducing the risk of mortality after myocardial infarction (MI). As a
      result, it is no longer ethical to test a new thrombolytic regimen against
      placebo. Rather, promising new therapies must be compared with proven treatments.
      This has been the direction taken in trials of reteplase, a new recombinant
      plasminogen activator. Initial studies of double-bolus reteplase demonstrated its
      superior ability to produce. TIMI grade 2 or 3 flow at 90 minutes when compared
      with accelerated alteplase. A subsequent randomized, double-blind, 9-country
      study, the International Joint Efficacy Comparison of Thrombolytics (INJECT)
      trial was designed to determine whether the efficacy of reteplase is at least
      equivalent to that of streptokinase. The 2 treatments were associated with
      similar frequencies of inhospital cardiac events, bleeding, and strokes.
      Likewise, no significant difference was apparent between the reteplase and
      streptokinase groups with regard to 35-day mortality (the primary endpoint), the
      combined endpoint of 35-day mortality plus continuing disability from inhospital
      stroke, or 6-month mortality. Unadjusted data from the 3 countries that
      contributed the majority of patients seemed to indicate a survival benefit,
      irrespective of treatment allocation, among patients who underwent interventional
      procedures. However, no such benefit was apparent when the data were adjusted for
      differences in the baseline characteristics of the patients enrolled in the
      different countries. Rather, intervention within the first 3 days post-MI was
      found to place patients at a substantially higher risk of 35-day mortality.
      Further insights into the relative efficacy of reteplase should emerge from the
      ongoing third Global Utilization of Strategies to Open Occluded Coronary Arteries
      (GUSTO-III) trial.

PMID- 8990408
TI  - Prognostic markers in thrombolytic therapy: looking beyond mortality.
AB  - In the era of multiple new therapies (e.g., aspirin, beta blockers, thrombolysis,
      angiotensin-converting enzyme inhibitors, etc.) with the potential to improve
      outcome, the utility of traditional methods for predicting risk for adverse
      outcome after acute myocardial infarction (MI) is being reevaluated. Recent data
      suggest that heart failure, male gender, older age, and ischemia on ambulatory
      electrocardiogram (ECG) monitoring are the best predictors for increased risk of
      death or nonfatal MI. Exercise stress testing and ejection fraction determination
      provide little, if any, additional prognostic information. A new, highly
      promising strategy is to assess the degree of resolution in ST-segment elevation
      on repeated ECG monitoring following thrombolytic therapy. Studies have shown
      that failure to achieve prespecified degrees of ST-segment resolution within the
      first few hours of thrombolytic therapy is a reliable indicator of risk for post
      MI mortality. Emerging data are also raising the possibility that cardiac
      troponin-T levels can be utilized as an important prognostic marker for adverse
      outcome in patients who present with acute ischemic syndromes.

PMID- 8990409
TI  - The search continues for accurate, useful dietary standards.

PMID- 8990410
TI  - Replacing fat with food technology. A brief review of new fat replacement
      ingredients.

PMID- 8990411
TI  - Looking ahead at public policy and the 105th Congress.

PMID- 8990412
TI  - Scientific evidence + professional judgment + translation = consistent
      carbohydrate?

PMID- 8990413
TI  - Fluid intake in the institutionalized elderly.
AB  - OBJECTIVE: Actual fluid intake in the institutionalized elderly was compared with
      three established standards to determine adequacy of fluid intake. DESIGN:
      Consecutive 3-day food and fluid intake was observed directly and analyzed by
      computer for water content. Number and frequency of medications and Minimum Data
      Set (MDS) information about cognitive skills, physical locomotion, and ability to
      understand were obtained from medical records. Recommended fluid intake was
      determined using three established standards for two age groups: 65 through 85
      years and 86 through 100 years. The standards were 30 mL/kg body weight (standard
      1); 1 mL/kcal energy consumed (standard 2); and 100 mL/kg for first 10 kg, 50
      mL/kg for next 10 kg, and 15 mL for remaining kg (standard 3). SUBJECTS/SETTING:
      Data were collected in one nursing home. Subjects were 40 residents who were free
      from acute illness and infection and/or were not receiving enteral feedings. MAIN
      OUTCOME MEASURES: Fluid intake and MDS data were collected. Data about
      medications were obtained after preliminary data collection observations.
      STATISTICAL ANALYSIS PERFORMED: A two-tailed t test was used to compare actual
      fluid intake with recommended fluid intake. Interaction effect of age on fluid
      intake was analyzed using multiple analysis of variance. Correlations were used
      to evaluate relationships among fluid intake, number and frequency of
      medications, age, weight, and MDS data. RESULTS: This population received
      adequate or more than adequate fluid according to the standards of 30 mL/kg body
      weight or 1 mL/kcal energy consumed, but inadequate fluid according to standard
      3, which adjusted for extremes of underweight or overweight. Age was not a factor
      in adequacy of fluid intake. Positive correlations existed between fluid obtained
      from nonmeal feedings and number and frequency of medications. APPLICATIONS: When
      the standard of 30 mL/kg body weight is used, underweight residents have
      unrealistically low fluid recommendations. Standard 3, which adjusts for extremes
      in body weight, is more reasonable for patients whether they are of normal
      weight, underweight, or overweight. This standard more closely supports other
      recommendations of 1,500 to 2,000 mL fluid intake per day. Number and frequency
      of medications influences the amount of fluid residents obtain during nonmeal
      feedings.

PMID- 8990414
TI  - "How do you remember you ate...?": a Delphi technique study to identify retrieval
      categories from fourth-grade children.
AB  - OBJECTIVE: To develop and validate a consensus set of retrieval categories for
      how children remember what they have eaten, and to relate retrieval categories to
      accuracy of reporting items eaten during school lunch. DESIGN: A Delphi technique
      study was conducted using 10 psychologists. The subject matter consisted of
      responses transcribed from interviews conducted with 89 randomly selected fourth
      graders within 90 minutes of eating. Retrieval categories were evaluated for
      accuracy by comparing students' self-reported lunch intake with observation.
      STATISTICAL ANALYSES: For round 1, a centroid hierarchical cluster analysis was
      used to identify common sets of rating pairs to propose categories for reaching
      consensus. For rounds 2 and 3, percent of agreement was calculated. Accuracy was
      tabulated across meal items and student use by retrieval category. RESULTS: After
      round 3, we found that 23 "near-consensus" categories were used by at least eight
      raters. Six categories were used 60% of the time, 4 were used 20% of the time,
      and 5 were used 15% of the time. Less frequently used categories were combined
      with similar, more frequently used categories for a total of 16 categories.
      Students used a large variety of retrieval categories when accurately reporting
      consumption. Of the 16 categories, 12 were used similarly by both accurate and
      inaccurate students. Where there were differences in accuracy by retrieval
      category, the more accurate students used "taste/smell/texture" and "visual" in
      deference to "order items consumed" and "oral cue still present." APPLICATIONS:
      These categories provide insight into the broad range of retrieval categories
      that children use and provide direction for researchers to design and study
      specific cues to enhance the accuracy of children's self-reports of diet.

PMID- 8990415
TI  - A worksite program for overweight middle-aged men achieves lesser weight loss
      with exercise than with dietary change.
AB  - OBJECTIVE: To compare changes in total and regional body composition using dual
      energy X-ray absorptiometry (DEXA) after subjects lost weight through change in
      diet or exercise. DESIGN: A 12-month, randomized, controlled study of two weight
      loss interventions-low-fat diet ad libitum or moderate, unsupervised exercise-in
      free-living, middle-aged men. Compliance was determined at monthly measurement
      sessions through food records and activity logs; DEXA scans were performed every
      3 months. SUBJECTS/SETTING: Fifty-eight overweight men (mean body mass index =
      29.0 +/- 2.6; mean age = 43.4 +/- 5.7 years) recruited from a national
      corporation were assigned randomly to diet, exercise, or control groups.
      INTERVENTIONS: One group reduced dietary fat to 26.4% of energy intake but kept
      activity unchanged; another group self-selected aerobic exercise (three sessions
      per week at 65% to 75% maximum heart rate) but kept diet unchanged. A control
      group maintained weight. MAIN OUTCOME MEASURES: At 12 months, measurements of
      weight, total and regional fat mass and lean mass, energy intake, and percentage
      dietary fat; physical activity indexes. STATISTICAL ANALYSES: Results were
      analyzed using paired t tests and analysis of variance. RESULTS: Mean weight loss
      was 6.4 +/- 3.3 kg in dieters and 2.6 +/- 3.0 kg in exercisers; control subjects
      maintained weight. DEXA scans revealed that 40% of dieters' weight loss was lean
      tissue; more than 80% of weight lost by exercisers was fat. Exercisers maintained
      limb lean tissue and lost fat mass. CONCLUSIONS: Greater total weight and lean
      tissue loss occurred when subjects lost weight through a low-fat diet consumed ad
      libitum than when subjects participated in unsupervised aerobic exercise. Use of
      DEXA enabled identification of progressive total and regional changes in fat and
      lean tissue.

PMID- 8990416
TI  - Translation of the diabetes nutrition recommendations for health care
      institutions: technical review.

PMID- 8990417
TI  - Translation of the diabetes nutrition recommendations for health care
      institutions: position statement. American Diabetes Association.

PMID- 8990418
TI  - The new biology of body weight regulation.
AB  - A growing body of evidence suggests that energy balance (the difference between
      energy intake and expenditure) and body fuel stores in the form of adipose tissue
      are maintained by the body within a narrow range. This regulation of adiposity is
      mediated by the secretion of hormonal signals into the circulation in proportion
      to body adipose stores and their subsequent actions on brain systems that control
      caloric intake and energy expenditure. As a result, changes in energy balance
      sufficient to alter fuel stores elicit compensatory changes in energy intake and
      expenditure that return fat stores to their regulated level. Recent scientific
      break-through have identified the key components of this physiologic system.
      These include the circulating signals, leptin (the hormone encoded by the ob gene
      that is secreted by fat cells) and the pancreatic hormone insulin; and brain
      peptides such as neuropeptide Y, which is released from nerve terminals in the
      hypothalamus to elicit changes in feeding behavior and energy expenditure that
      mediate adaptive changes in energy balance. This article reviews the discovery of
      leptin and its receptor and discusses the interaction of leptin and insulin with
      the hypothalamic neuropeptide Y system. These observations provide a basis for
      understanding how weight lost during a period of negative energy balance (because
      of the inability to consume and/or store sufficient energy to meet ongoing energy
      demands) is eventually recovered. As our understanding of this weight-regulatory
      system increases, new insights into the causes of human obesity are likely to
      follow. Such insights may yield improvements in the medical and nutrition
      management of obese patients.

PMID- 8990419
TI  - Clinical pathway nutrition management for outpatient bone marrow transplantation.

PMID- 8990420
TI  - Attitudes of registered dietitians toward personal overweight and overweight
      clients.

PMID- 8990421
TI  - Low validity of a seven-item fruit and vegetable food frequency questionnaire
      among third-grade students.

PMID- 8990422
TI  - Assessing food purchase behavior among low-income black and Hispanic clients
      using a self-reported shelf inventory.

PMID- 8990423
TI  - Position of the American Dietetic Association: weight management.

PMID- 8990424
TI  - President's page: technology--the bridge to the 21st century.

PMID- 8990425
TI  - Report on the American Dietetic Association's member needs
      assessment/satisfaction study. Member Needs Assessment/Satisfaction Study
      Steering Committee.

PMID- 8990426
TI  - CPR: can we be resuscitated?

PMID- 8990427
TI  - Effect of intramuscular 15-methyl prostaglandin F2 alpha after second-trimester
      delivery.
AB  - OBJECTIVE: To determine whether 15-methyl prostaglandin (PG) F2 alpha shortens
      the third stage of labor in second-trimester pregnancy loss. METHODS: This was a
      randomized, double-blind, placebocontrolled study of women between 13 and 28
      weeks' gestation admitted for spontaneous or induced pregnancy termination.
      Subjects were randomized on admission to receive either PG (250 micrograms) or
      placebo (normal saline), 1 mL intramuscularly every 20 minutes, for a maximum of
      three doses if the placenta had not delivered spontaneously within 10 minutes of
      the fetus. A dilute oxytocin infusion was given to women in both groups. The
      patients were managed expectantly with hourly vaginal examinations until
      intervention was required or up to 6 hours, when curettage was scheduled.
      RESULTS: Thirty-eight women received PG and 29 received placebo. There was no
      difference between the groups with regard to method of pregnancy termination or
      gestational age. There was a statistically significant decrease in the time from
      first injection to placental delivery (40.0 versus 92.5 minutes; P = .02) between
      the PG and control groups, respectively. CONCLUSIONS: The therapeutic use of PG
      in the third stage of labor in second-trimester pregnancy loss reduces the time
      to complete spontaneous placental delivery.

PMID- 8990428
TI  - Effects of a partially home-based exercise program for women with gestational
      diabetes.
AB  - OBJECTIVE: To examine the effectiveness of a partially home-based, moderate
      intensity aerobic exercise program for women with gestational diabetes. METHODS:
      This was a randomized experimental design. Thirty-three women with gestational
      diabetes were randomly assigned to the exercise or the no-exercise group.
      Subjects underwent hemoglobin A1C assay and submaximal cycle ergometer fitness
      tests at baseline and at study conclusion. Subjects kept diaries of home fasting
      and 2-hour postprandial blood glucose determinations. Exercise subjects were
      asked to exercise for 30 minutes three to four times weekly at 70% of estimated
      maximal heart rate for the weeks of study participation. Two exercise sessions
      weekly were supervised by the investigator, and two were unsupervised at home.
      Control-group subjects were asked to maintain their current activity level.
      RESULTS: Daily fasting and postprandial blood glucose levels, hemoglobin A1C,
      incidence of exogenous insulin therapy, and incidence of newborn hypoglycemia
      were not different between the groups. There was a training effect in the
      exercise group (P = .005) but not in the control group (P = .25). A significant
      decline in daily grams of carbohydrate consumed was observed in the control group
      (P = .03), but not in the exercise group (P = .97). No complications were found
      in the subjects who exercised. CONCLUSIONS: A partially home-based exercise
      program did not reduce blood glucose levels, but did result in a modest increase
      in cardiorespiratory fitness. The intervention appeared safe.

PMID- 8990429
TI  - One- versus two-layer closure of a low transverse cesarean: the next pregnancy.
AB  - OBJECTIVE: To determine whether a low transverse cesarean closure method in one
      or two layers affects subsequent pregnancy outcome. METHODS: In a prospective
      trial reported previously, 906 women were assigned randomly to either one- or two
      layer uterine closure. One hundred sixty-four women had a subsequent pregnancy
      and delivery (18 weeks' gestation or longer) at our institution. Maternal and
      neonatal outcomes were ascertained by medical chart review and compared between
      the one- and two-layer closure groups. RESULTS: Of the 164 subsequent deliveries,
      83 had previous closure in one layer, whereas 81 had involved a two-layer
      closure. The demographic characteristics of these two groups were similar.
      Nineteen women (12%) underwent elective repeat cesareans without labor, and the
      remaining 145 experienced labor. Length of labor, mode of delivery, duration of
      hospital stay, gestation at delivery, and the incidences of uterine scar
      dehiscence, chorioamnionitis, postpartum metritis, hemorrhage, transfusion, and
      abnormal placentation did not differ significantly between the groups. Selected
      neonatal outcomes, including Apgar scores, cord pH, birth weight, and perinatal
      death, were similar between groups as well. CONCLUSIONS: These findings suggest
      that the type of low transverse cesarean closure does not significantly affect
      the outcome of the next pregnancy.

PMID- 8990430
TI  - Brain tumor and pregnancy.
AB  - OBJECTIVE: To establish the indications for surgical intervention, at the
      appropriate gestational duration, for brain tumors in pregnant women, and to
      evaluate any association pregnancy hormones may have with the rate of growth or
      development of complications of brain tumors. METHODS: We observed seven women
      with brain tumors associated with pregnancy in a series of 126,413 pregnancies
      from 1983 to 1995. One woman presented with symptoms of intracranial
      hypertension, and neurologic signs were the first symptoms in two other women.
      One woman presented with a sudden hemorrhagic lesion, and three had focal
      seizures. All were evaluated with computed tomography, magnetic resonance
      imaging, or both. RESULTS: Six of the seven women had surgery; the seventh was
      treated with radiotherapy because the neuroradiologic studies suggested a quickly
      growing brainstem glioma. Diagnoses were confirmed on histology in six women: two
      with meningiomas, two with ependymomas, and two with low-grade astrocytomas (one
      of these had multiple astrocytomas). Estrogen and progesterone receptors were
      studied in two cases (one meningioma and one astrocytoma) and were present in
      both. CONCLUSION: Management of brain tumors should be tailored to the individual
      patient. There may be a relation between pregnancy hormones and the rate of brain
      tumor growth mediated through specific intracellular receptors.

PMID- 8990431
TI  - Serum ionized magnesium levels in normal and preeclamptic gestation.
AB  - OBJECTIVE: To compare serum levels of ionized and total magnesium with those of
      ionized calcium, total calcium, sodium, and potassium over the course of
      pregnancy in normal women and in women who develop preeclampsia. METHODS: We
      collected venous serum samples from 31 pregnant women during their first, second,
      and third trimesters. Gestational ages ranged from 6 to 37 weeks. Samples were
      analyzed for ionized and total magnesium, ionized and total calcium, sodium, and
      potassium using a biomedical chemistry analyzer. Data were analyzed with repeated
      measures analysis of variance and two-way repeated-measured analysis of variance.
      RESULTS: In 22 normal pregnant women, both serum ionized and total magnesium
      levels decreased significantly with increasing gestational age. No changes in
      sodium, potassium, or ionized or total calcium were observed. Nine of the 31
      subjects developed preeclampsia by term; serum total magnesium levels decreased
      significantly by the second trimester in these women compared with those of
      normal pregnant women. CONCLUSION: Our results provide evidence of decreases in
      ionized and total magnesium levels with increasing gestational age during normal
      pregnancy, as well as evidence of a magnesium disturbance in women who later
      develop preeclampsia. Future studies of magnesium balance in women at risk for
      developing complications of pregnancy are indicated.

PMID- 8990432
TI  - Prevention practices for perinatal group B streptococcal disease: a multi-state
      surveillance analysis. Neonatal Group B Streptococcal Disease Study Group.
AB  - OBJECTIVE: To evaluate hospital-based practices for perinatal group B
      streptococcal disease prevention and to identify institutional factors related to
      the disease. METHODS: We surveyed microbiology laboratories and obstetric
      programs during 1994 at hospitals in five states with active surveillance for
      invasive group B streptococcal disease. Institutions provided information on
      methods for detecting carriers and on obstetric policies for group B
      streptococcal disease prevention. We used linear regression to identify
      prevention practices and hospital characteristics that correlated with the number
      of cases of early-onset disease. RESULTS: Of 295 hospitals, 247 (84%)
      laboratories and 154 (52%) obstetric programs completed the survey. Most (83%)
      laboratories performed group B streptococcal cultures on rectal and vaginal
      specimens, but only 12 (6%) used selective broth media. Among the obstetric
      programs, 54 (35%) had policies on some aspect of group B streptococcal disease
      prevention. Of the hospitals with policies, 21 (48%) recommended intrapartum
      antimicrobial prophylaxis for women with risk factors outlined by the 1992 ACOG
      statement. Adjusting for the number of births, there were more cases of early
      onset group B streptococcal disease in institutions providing care for more
      African American women and for more women with no prenatal care. Institutions
      that had group B streptococcal screening policies had fewer early-onset cases.
      CONCLUSIONS: Many institutions with prevention policies followed practices that
      differed from those recommended in published prevention statements. Having any
      screening policy, however, was associated with reduced early-onset disease,
      independent of the risk profile of the patient population. Adopting prevention
      policies is most urgent for practices serving individuals at increased risk, such
      as African American women and women without prenatal care.

PMID- 8990433
TI  - Fetal death rate in the United States, 1979-1990: trend and racial disparity.
AB  - OBJECTIVE: To examine the impact of changes in birth weight distribution in
      individual groups and in birth weight-specific fetal death rates on the decline
      in the crude fetal death rate in the United States. METHODS: Data on live births
      and fetal deaths in the U.S. for the period 1979-1990 were examined by birth
      weight group and race using Kitagawa's method for analysis of the crude fetal
      death rate. RESULTS: In the period 1979-1990, all racial groups had a decrease in
      the crude fetal death rate, more so in whites and others (about 22%) than in
      blacks (10%). In the white population, 73.4% of the total reduction in the crude
      fetal death rate was attributable to the improvement in birth weight-specific
      fetal death rates, and the remaining portion of the reduction was due to a
      favorable change in birth weight distribution. In the black population, the
      reduction in the crude fetal death rate was entirely attributable to the
      improvement in the birth weight-specific fetal death rates. However, in other
      groups, a favorable change in the birth weight distribution was the major
      determinant. Although black births represented 16.5% of all births in the U.S.,
      they accounted for 26-29% of the crude fetal death rate. Disparity in the crude
      fetal death rates for blacks and whites is explained almost entirely by
      differences in birth weight distribution. CONCLUSIONS: A further decrease in the
      crude fetal death rate in the U.S. requires a decrease in low birth weights,
      particularly in blacks.

PMID- 8990434
TI  - Causes of fetal death in women of advanced maternal age.
AB  - OBJECTIVE: To examine which causes of fetal death occur more often in older women
      and to determine whether these causes have changed significantly since the 1960 s
      and early 1970 s. METHODS: Data from the McGill Obstetrical Neonatal Database
      were used to calculate rates of specific causes of fetal death in women younger
      than 35 and in women 35 years or older. Among the 101,640 births between 1961 and
      1995, there were 715 stillbirths and 822 neonatal deaths. The autopsy rate was
      97% and categorization of the causes of fetal death remained consistent over this
      34-year period. The rates of specific causes of fetal death per 10,000 total
      births were determined for an earlier period (1961-1974) and a later period (1978
      1995). RESULTS: Compared with the 1961-1974 period, there was a 60% reduction in
      the rates of both fetal and neonatal deaths during 1978-1995 (P < .001). During
      1961-1974, women 35 years or older were more likely than their younger counter
      parts to have fetal death due to lethal congenital anomalies (odds ratio [OR]
      3.2; 95% confidence interval [CI] 1.5, 6.5); this was no longer true in the 1978
      1995 period. From 1978 to 1995, older women were at a statistically significant
      increased risk for "unexplained" fetal death (OR 2.2; 95% CI 1.3, 3.8); women 35
      years of age or older had approximately one in 440 births end in unexplained
      fetal death, compared to one in 1000 births for women younger than 35.
      CONCLUSIONS: Advanced maternal age is no longer associated with an increased risk
      for fetal death due to congenital anomalies. However, older women have a
      significantly higher risk for unexplained fetal death. The identification of
      those maternal and fetal characteristics that contribute to unexplained fetal
      death and its prevention remain important challenges for contemporary obstetric
      practice.

PMID- 8990435
TI  - Fetal plasma levels of cellular fibronectin as a measure of fetal endothelial
      involvement in preeclampsia.
AB  - OBJECTIVE: To determine the degree of fetal endothelial involvement in
      preeclampsia by measuring fetal plasma concentrations of cellular fibronectin.
      METHODS: In a prospective cohort study, fetal plasma was collected at delivery
      from the chorionic plate arteries and veins in a convenience sample of 28
      pregnancies complicated by preeclampsia and in 28 normal pregnancies. Stored
      plasma was assayed for cellular fibronectin using a sensitive and specific enzyme
      immunoassay. On the basis of a desired power of 0.8, alpha of .05, and expected
      fetal plasma cellular fibronectin values of 4 +/- 2 micrograms/mL, 26 women were
      required in each group to detect a 40% difference between the groups. Results
      were compared using the unpaired Student t test, chi 2 analysis with Yates
      correction, and linear regression. RESULTS: There was no statistically
      significant difference in fetal plasma concentrations of cellular fibronectin in
      women with preeclampsia compared with normal pregnant women, either in arteries
      (3.2 +/- 1.1 and 2.9 +/- 1.5 micrograms/mL; P = .33) or veins (3.3 +/- 1.5 and
      2.8 +/- 1.6 micrograms/mL; P = .18). Plasma cellular fibronectin concentrations
      in fetal arteries correlated significantly with those in fetal veins (r = 0.45, P
      < .001), but not with those in maternal veins (r = 0.15, P = .27). CONCLUSION:
      Fetal plasma cellular fibronectin concentrations are similar in preeclamptic and
      normal pregnancies. We found no evidence that factors responsible for maternal
      endothelial involvement in preeclampsia are operative in the fetal circulation.

PMID- 8990436
TI  - Placental nitric oxide synthase activity and abnormal umbilical artery flow
      velocity waveforms.
AB  - OBJECTIVE: To assess the nitric oxide synthase activity in placentas from women
      with either normal or abnormal Doppler ultrasound umbilical artery flow velocity
      wave-forms who delivered by elective cesarean. METHODS: This prospective
      observational study involved 16 women admitted either for elective cesarean for
      standard obstetric indications (with normal umbilical artery Doppler waveform
      studies, n = 8) or with evidence of fetal or maternal complications of pregnancy
      (with abnormal umbilical artery Doppler studies, n = 8). Placental tissue was
      collected and frozen in liquid nitrogen immediately upon delivery. Following
      storage at -80C, nitric oxide synthase activity was analyzed by measuring the
      conversion of [3H]L-arginine to [3H]L-citrulline. RESULTS: Placentas from women
      with abnormal umbilical artery flow velocity waveforms showed significantly lower
      mean nitric oxide synthase activity than did placentas from women with normal
      umbilical artery flow velocity wave-forms (Vmax = 11.3 pmol/minute/mg protein
      versus 22.6 pmol/minute/mg protein). CONCLUSION: There is a statistically
      significant reduction in nitric oxide synthase activity in placentas from
      pregnancies with abnormal umbilical artery flow velocity waveforms.

PMID- 8990438
TI  - The effect of intrauterine transfusion on fetal bilirubin in red cell
      alloimmunization.
AB  - OBJECTIVE: To evaluate the change in fetal serum bilirubin levels in response to
      intrauterine transfusion for red cell alloimmunization. METHODS: The records of
      37 patients who underwent more than one intrauterine transfusion were reviewed.
      The following indices were extracted: pre- and post-transfusion fetal hematocrit,
      total and direct serum bilirubin, reticulocyte count, Kleihauer-Betke test
      results, volumes of intravascular and intraperitoneal transfusions, and the
      source used for transfusion. The data were compared for interval 1 (transfusion 1
      to 2) and interval 2 (transfusion 2 to 3). The rates of change in bilirubin,
      reticulocyte count, and percent fetal cells on the Kleihauer-Betke test were
      defined as the differences between the initial values of one transfusion and the
      initial values of the next transfusion divided by the number of days between
      transfusions. Analysis of variance, sign-rank test, and linear regression
      analysis were used when appropriate. P < .05 was significant. RESULTS: The median
      number of intrauterine transfusions for each patient was 3 (range 2-8).
      Gestational ages ranged from 22 to 37 weeks. Total bilirubin remained above the
      97.5 percentile for gestational age in all but five patients. There was a
      significant decrease in reticulocyte count and fetal cells on the Kleihauer-Betke
      test, and an increase in hematocrit with serial intrauterine transfusions.
      Bilirubin increased significantly after the first intrauterine transfusion (3.9
      versus 5.0 mg/dL) and remained elevated thereafter. CONCLUSION: Fetal total serum
      bilirubin remains elevated with repeated intrauterine transfusions in fetal
      alloimmunization. Total bilirubin should not be used to evaluate fetal
      hematologic responses to the transfusions.

PMID- 8990437
TI  - Ovine fetal umbilical artery Doppler systolic diastolic ratios and nitric oxide
      synthase.
AB  - OBJECTIVE: To evaluate the effect of nitric oxide synthase activity inhibition on
      the fetal lamb umbilical artery flow velocity waveform. METHODS: Five pregnant
      Corriedale cross ewes were operated on at 125-130 days' gestation. Fetal and
      maternal vascular catheters were inserted along with a Doppler flow meter cuff on
      the fetal common umbilical artery. Each fetus received a 40-minute intravenous
      (i.v.) infusion of N omega-nitro-D-arginine as a control, and then after a
      recovery period of 1 hour, a 40-minute i.v. infusion of N omega-nitro-L-arginine,
      an inhibitor of nitric oxide synthase activity. Maternal and fetal heart rate,
      blood pressure, blood gases, and fetal umbilical artery flow velocity waveforms
      were recorded at basal time and after the 40-minute i.v. infusions. RESULTS:
      There were no differences in fetal or maternal heart rate, blood pressure, or
      blood gases with the infusion of the nitric oxide synthase inhibitor N omega
      nitro-L-arginine. However, N omega-nitro-L-arginine caused a significant increase
      (41%) in the fetal umbilical artery flow velocity waveform systolic to diastolic
      ratio (S/D) above the baseline levels. CONCLUSIONS: Inhibition of nitric oxide
      synthase activity in the lamb fetoplacental circulation with N omega-nitro-L
      arginine is associated with an increase in the umbilical artery S/D.

PMID- 8990439
TI  - Attitudes and educational practices of obstetric providers regarding infant
      hepatitis B vaccination.
AB  - OBJECTIVE: To survey the current knowledge, attitudes, and practices of obstetric
      providers regarding the education of pregnant women about infant hepatitis B
      vaccination. METHODS: A questionnaire was mailed to 264 physicians providing
      obstetric services in San Francisco. Of these, 113 were confirmed to be providing
      prenatal care. RESULTS: Seventy-six obstetric providers returned completed
      questionnaires. Among eligible respondents, 79% believed that hepatitis B vaccine
      should be administered to all infants at birth, and 92% believed that it is
      feasible to educate all expectant mothers about infant hepatitis B vaccination.
      However, only 53% of respondents provided such education to all their pregnant
      patients. Only 23% provided education about other routine childhood
      immunizations. CONCLUSIONS: Obstetric providers in San Francisco are willing to
      educate pregnant patients about hepatitis B vaccination but are not always doing
      so. Providing education in a consistent manner may improve infant hepatitis B
      vaccination rates and may increase coverage with other childhood vaccines.

PMID- 8990440
TI  - Pelvic inflammatory disease and human immunodeficiency virus infection.
AB  - OBJECTIVE: To identify the effect of human immunodeficiency virus (HIV) infection
      on the clinical course of pelvic inflammatory disease (PID). METHODS: Women
      hospitalized with PID at an urban hospital serving a population at high risk for
      HIV were studied cross-sectionally. Data abstracted from medical records of 349
      women, admitted between July 1992 and April 1994 were linked anonymously to HIV
      serology. Main outcome measures were length of hospital stay, prolonged fever,
      tubo-ovarian abscess, surgery, and change in antibiotics. RESULTS: Among the 349
      women with PID, 27 were HIV-positive. These HIV-positive women had lower mean
      white blood cell counts at admission (7411 versus 11,266, P < .01), lower mean
      lymphocyte counts (1411 versus 1928, P < .01), greater febrile morbidity (54
      versus 28.3%, P < .01), and longer hospital stays (10.5 versus 6.4 days, P < .01)
      than HIV-negative women. Women who were HIV-positive required more time for
      defervescence and needed to change their antibiotic regimen more frequently (41
      versus 12.7%, P < .01); differences in tubo-ovarian abscesses (19 versus 14%, P =
      .52) or surgery (15 versus 6.2%, P = .10) were not significant. The differences
      in hospital course between HIV-positive and HIV-negative women were modest, and
      they were resolved largely by the fourth or fifth hospital day. All HIV-positive
      women were treated successfully with first- or second-line antibiotic regimens.
      CONCLUSION: Despite more severe initial presentation and a prolonged hospital
      course, HIV-positive women with PID, but without other acute illnesses, were
      treated successfully with standard therapeutic regimens. These observations
      support current recommendations for hospitalization of HIV-positive women with
      PID and treatment according to current standards.

PMID- 8990441
TI  - Cervical abnormality and sexually transmitted disease screening in human
      immunodeficiency virus-positive women.
AB  - OBJECTIVE: To determine the incidence of genital tract infections and cervical
      abnormalities in 185 human immunodeficiency virus (HIV)-positive outpatients with
      a view toward establishing an effective policy for gynecology screening. METHODS:
      Gynecology results were reviewed for 185 HIV-positive women seen as outpatients
      at the Royal Free Hospital in London. All subjects underwent screening for
      cervical abnormalities (smear and colposcopy) and sexually transmitted disease
      (STD) at 6-month intervals for 6 years. The STD prevalence was calculated, and
      the relationship between the occurrence of STDs and the demography and sexual
      lifestyle of the women was examined to determine whether these factors were
      predictive for women at risk for STDs. The incidence of cervical intraepithelial
      neoplasia (CIN) was determined. We reviewed the use of colposcopy in addition to
      cytology as a primary screening test to see whether it improved the detection
      rate of CIN. RESULTS: Sixty-five (35.1%) women had a history of previous STDs,
      and new STDs were detected in 18 women at their first visits. None were detected
      at subsequent visits. Sexual lifestyle details did not predict women at risk for
      STDs. Ninety-eight (53%) cervical smears were reported as normal at the first
      visit, but there was a 3.1% (95% confidence interval 0, 6.6) false-negative rate
      when compared with colposcopy and directed biopsy. Five of fifty women (10%) with
      CIN I had progressed to higher-grade lesions by 6-month follow-up. CONCLUSIONS:
      Given the low prevalence of STDs detected, except for initial screening at
      presentation, regular, repeat STD screening of HIV-positive women appears to be
      unnecessary. Because of the high incidence of cervical abnormalities, screening
      for cervical biopsy improved the detection rate of cervical abnormalities.

PMID- 8990442
TI  - Cervical cancer as an AIDS-defining illness.
AB  - OBJECTIVE: To evaluate the importance of cervical cancer in the spectrum of human
      immunodeficiency virus (HIV)-related diseases at a single high-risk institution
      and to compare disease characteristics in HIV-infected women with cervical cancer
      and those with other AIDS-related malignancies. METHODS: We retrospectively
      reviewed data on cervical cancer and AIDS in women registered through the New
      York City Department of Health and institutional tumor registries from 1987
      through 1995. RESULTS: During the study period, cervical cancer was diagnosed in
      28 HIV-positive women. In 26, cervical cancer was the initial AIDS-defining
      illness, representing 4% (26 of 725) of the subjects, and it was the sixth most
      common initial AIDS-defining illness in women. Cervical cancer was the most
      common AIDS-related malignancy among women, representing 55% of the cases,
      followed by lymphoma (29%) and Kaposi sarcoma (16%). In 71% of the women with
      cervical cancer, HIV infection was diagnosed at the time of cancer presentation
      by routine testing, whereas in women with other malignancies, HIV diagnosis
      preceded cancer diagnosis (70%) by a mean of 2.7 years. Patients with other
      malignancies had greater immunosuppression (mean CD4 count 153/microL) than those
      with cervical cancer (mean CD4 count 312/microL). The recurrence rate for women
      with cervical cancer was 88%. Although the interval from cancer diagnosis to
      death was similar in all three groups (9.1-12.4 months), cancer was the cause of
      death in 95% of HIV-infected women with cervical cancer, compared with 60% of
      those with other AIDS-related malignancies. CONCLUSION: In urban populations at
      increased risk for both diseases, cervical cancer is an important AIDS-defining
      illness and may be the most common AIDS-related malignancy in women.

PMID- 8990443
TI  - Human papillomavirus in squamous cell carcinoma of the vulva by polymerase chain
      reaction.
AB  - OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) DNA in
      squamous cell carcinoma of the vulva by polymerase chain reaction (PCR). METHODS:
      Archival diagnostic phase biopsies from 74 patients with squamous cell carcinoma
      of the vulva were investigated for HPV DNA by PCR. We used both consensus primers
      located in the open reading frame L1 and type-specific primers for HPV 6 (open
      reading frame E5), HPV 11 (open reading frame L1), HPV 16, HPV 18, and HPV 33
      (open reading frame E6). RESULTS: HPV DNA was detected in 27 (36%) of the 74
      patients, of whom 19 had HPV 16, nine had HPV 18, one had HPV 33, and one had
      unclassified HPV DNA. No case of HPV type 6 or 11 was detected. Two squamous cell
      carcinomas were positive for both HPV 16 and 18, and one was positive for both
      HPV types 16 and 33. Three squamous cell carcinomas positive for E6 gene using
      type-specific primers were negative using L1 consensus primers. CONCLUSION: Our
      PCR methods using both consensus open reading frame L1-derived primers and type
      specific open reading frame E6-derived primers of HPV types 16, 18, and 33 seemed
      to be an appropriate combination for the detection of HPV DNA in archival tissues
      of vulvar carcinoma. Both HPV types 16 and 18 were associated with squamous cell
      carcinoma of the vulva, although the prevalence of HPV 16 was considerably lower
      than in cervical carcinoma. It appears that vulvar and cervical carcinomas are
      not identical etiologically and that factors other than HPV are important in
      vulvar carcinogenesis.

PMID- 8990444
TI  - Ovarian and uterine disease in women with colorectal cancer.
AB  - OBJECTIVE: To identify the nature of adnexal and uterine disease in women with a
      history of colorectal adenocarcinoma who develop new pelvic masses or uterine
      cancers during follow-up. METHODS: We conducted a retrospective chart review of
      the Memorial Hospital Gynecology Service database and identified 50 women, each
      with a history of colorectal carcinoma who underwent a hysterectomy or
      adnexectomy between January 1, 1977, and February 29, 1996. Subject
      characteristics, indications for re-operation, and findings at surgery were
      recorded. RESULTS: The mean age at re-operation was 66 years (range, 37-76), with
      a median interval from initial diagnosis to re-operation of 25 months (range, 3
      444). Indications for re-operation were: 1) new pelvic mass in 35 women, and 2)
      cancer on endometrial or cervical biopsy in 15. Twenty-six of the 35 (74%) women
      who presented with a pelvic mass had a malignancy in the ovary, with metastatic
      colon cancer noted in 20 of 26 (77%) women, and epithelial ovarian cancer in six
      of 26 (23%). The mean ovarian tumor size for metastatic colorectal carcinoma,
      ovarian cancer, and benign tumors was 15, 8, and 6 cm, respectively. Fifteen
      women underwent hysterectomy for a newly diagnosed cancer in the uterus, with the
      majority, 11 (73%), having endometrial adenocarcinoma, followed by metastatic
      colon cancer to the endometrium or cervix in three (20%) women, and primary
      cervical carcinoma in one. CONCLUSION: Women with a history of colorectal cancer
      who underwent adnexectomy for a new pelvic mass had metastatic colon cancer to
      the ovary in 57%, benign ovarian neoplasm in 26%, and primary ovarian cancer in
      17% of cases. Women who underwent hysterectomy for a newly diagnosed carcinoma in
      the uterus had primary endometrial adenocarcinoma in 73% and metastatic colon
      cancer in 20% of cases.

PMID- 8990445
TI  - Microinvasive adenocarcinoma of the cervix: a clinicopathologic study of 77
      women.
AB  - OBJECTIVE: To prove that microinvasive adenocarcinoma of the cervix exists and,
      like its squamous counterpart, carries an excellent prognosis. METHODS: Seventy
      seven women with microinvasive adenocarcinoma of the cervix were seen from 1971
      to 1995. Microinvasion was defined as depth of invasion or tumor thickness of at
      most 5 mm. Microscopic assessment was made on punch biopsies, serially sectioned
      conization specimens, and extensively sampled hysterectomy specimens. RESULTS:
      Most of the women had abnormal Papanicolaou smears. We made definitive diagnoses
      on conization specimens in 49 women, hysterectomy specimens in 22, and
      colposcopically directed punch biopsies in six (three being no residual disease
      in the subsequent conization-hysterectomy specimens). The length of microinvasive
      adenocarcinomas ranged from 0.8 to 21 mm, and the volume was between 3 and 1000
      mm. The tumors were multicentric in 21 cases, but no true "skip" lesions were
      found. Overall, 58 cold-knife conizations were performed: the margins were free
      in 39 cases, involved in 18, and inconclusive in one. The one loop conization had
      involved margins. Definitive therapy included cold-knife conization in 16 women,
      combined with pelvic-node dissection in four. In the remainder of the women, we
      performed some type of hysterectomy. None of the 26 women who had radical
      hysterectomy had parametrial spread, and none of the 48 who had pelvic-node
      dissection or the 23 in whom one or both adnexa were removed had metastases.
      There have been two "recurrences" to date; one was an adenocarcinoma and the
      other a squamous cell carcinoma, both at the vault. CONCLUSION: Microinvasive
      adenocarcinoma of the cervix is a clinicopathologic entity that appears to have
      the same prognosis, and should be treated in the same way, as its squamous
      counterpart.

PMID- 8990446
TI  - Sacrospinous ligament fixation with transvaginal needle suspension for advanced
      pelvic organ prolapse and stress incontinence.
AB  - OBJECTIVE: To assess the results of sacrospinous ligament fixation with
      transvaginal needle suspension for the correction of advanced pelvic organ
      prolapse and stress incontinence. METHODS: Ninety-six women who had pelvic organ
      prolapse to or beyond the hymen with or without stress incontinence were
      surgically managed over 3.5 years. Objective follow-up was available on 75 women.
      The subject group comprised 54 of these women who had stress incontinence and
      underwent sacrospinous ligament fixation with transvaginal needle suspension. The
      remaining 21 women who did not have stress incontinence underwent sacrospinous
      ligament fixation and served as controls. Appropriate vaginal repairs were
      performed as needed in both groups. RESULTS: The mean duration of follow-up was
      24 months (range 7-72) for the subjects compared with 24.3 months (range 3-53)
      for the controls. Eighteen subjects (33%) developed recurrent prolapse to or
      beyond the hymen. Additionally, five (9%) subjects developed recurrent stress
      incontinence and nine (17%) complained of urge incontinence. Four (19%) controls
      developed recurrent prolapse, two of whom also have urge incontinence. There was
      no statistical difference in the mean duration of follow-up or the incidence of
      recurrent prolapse between subjects and controls. CONCLUSION: Despite the absence
      of statistical significance, we believe that the 33% recurrent prolapse rate
      associated with sacrospinous ligament fixation and transvaginal needle suspension
      is clinically important.

PMID- 8990447
TI  - Differing responses in blood pressure over 24 hours in normotensive women
      receiving oral or transdermal estrogen replacement therapy.
AB  - OBJECTIVE: To examine the effects of oral and transdermal estrogen replacement
      therapy (ERT) on ambulatory 24-hour blood pressure (BP) recordings. METHODS: In a
      nonrandomized, prospective study, 90 normotensive, oophorectomized women, ages 30
      59 years, underwent ambulatory 24-hour BP measurements at study entry and after 3
      and 6 months of either oral (n = 50) or transdermal (n = 40) ERT. RESULTS: In the
      women receiving transdermal estrogen, we observed a change in mean nighttime
      systolic BP of -4.2 mmHg (95% confidence interval [CI] -7.7, -0.7; P = .039)
      after 6 months, treatment. There was a change in mean daytime diastolic BP after
      3 months (-3.3 mmHg; 95% CI -5.5, -0.9; P = .016) and 6 months (-4 mmHg; 95% CI
      6.8, -1.2; P = .014), and in mean nighttime diastolic BP after 3 months (-3.8
      mmHg; 95% CI -6.6, -0.9; P = .027) and 6 months (-4.4 mmHg; 95% CI -7.1, -1.7; P
      = .005). No significant BP changes were observed in the women taking oral
      estrogen. Although the statistical power to detect a change of 4 mmHg at the 5%
      significance level was 90% for diastolic BP, it was weaker for systolic BP (63%)
      in this group. However, in more than one-third of the women receiving either
      treatment, a statistically significant increase in BP was observed. CONCLUSIONS:
      Transdermal ERT was associated with a reduction in mean ambulatory BP, whereas
      oral treatment did not alter BP. Although the overall effect of estrogen was to
      lower BP, individual responses were variable, and BP increased in more than one
      third of the women on either treatment. Therefore, long-term monitoring of
      ambulatory measurements may be required.

PMID- 8990448
TI  - Different effects of oral and transdermal hormonal replacement on prostacyclin
      and thromboxane A2.
AB  - OBJECTIVE: To elucidate the mechanism of cardiovascular protection of hormone
      replacement therapy (HRT) by comparing the effect of oral and transdermal HRTs on
      the production of antiaggregatory, vasodilatory prostacyclin, and its endogenous
      antagonist, thromboxane A2. METHODS: Oral estradiol (2.0 mg/d) plus
      norethisterone acetate (1.0 mg/d) (n = 13) or transdermal estradiol (50
      micrograms/d) plus medroxyprogesterone acetate (10 mg/d) as 12-day courses at 4
      week intervals (n = 13) were given to postmenopausal women. Urinary excretion of
      the metabolites of prostacyclin, ie, 6-ketoprostaglandinF1 alpha and 2,3-dinor-6
      ketoprostaglandinF1 alpha, as well as those of thromboxane A2, ie, thromboxane B2
      and 2,3-dinor-thromboxane B2, were measured by radioimmunoassays, after
      purification by extraction and high performance liquid chromatography, before and
      during the sixth and the 12th treatment cycles. RESULTS: Oral HRT stimulated
      excretion of thromboxane B2 from 3.4 +/- 0.7 ng/mmol creatinine to 4.5 +/- 1.5
      (mean +/- standard deviation, P < .05) and that of 2,3-dinor-thromboxane B2 from
      16.6 +/- 8.0 ng/mmol creatinine to 26.2 +/- 10.7 (P < .01), and thus led to the
      dominance of thromboxane A2. No changes in prostanoids occurred during
      transdermal HRT. CONCLUSIONS: The effects of various HRTs on prostanoids may
      significantly differ.

PMID- 8990449
TI  - A nationwide analysis of laparoscopic complications.
AB  - OBJECTIVE: To evaluate the nationwide incidence of laparoscopic complications, as
      the number of demanding gynecologic laparoscopic procedures increases worldwide.
      METHODS: The National Patient Insurance Association was founded in 1987 in
      Finland. All major complications are reported to the Association because it
      handles financial compensation for patients' injuries without proof of
      malpractice. We analyzed 256 complications following laparoscopic procedures
      occurring in 1990-1994. There were 160 minor complications, which were defined as
      mild infections, mild hemorrhages, and failed sterilization. In all, 96 major
      complications occurred, including intestinal, urinary tract, and vascular
      injuries. The number of gynecologic laparoscopies (70,607 procedures) was
      obtained from the Finnish Hospital Discharge Register. RESULTS: The total
      complication rate was 3.6/1000 procedures, and the rate of major complications
      was 1.4/1000 procedures. In diagnostic laparoscopies, the annual major
      complication rate was constantly below 0.6/1000, and in sterilization, it was
      below 0.8/1000. In operative laparoscopies, major complications increased from
      0/1000 in 1990 to 10.5/1000 in 1993 and leveled to 10.1/1000 in 1994. In all,
      intestinal injuries occurred in 0.6/1000, ureteral injuries in 0.3/1000, bladder
      injuries in 0.3/1000, and vascular injuries in 0.1/1000 laparoscopic procedures.
      CONCLUSIONS: Diagnostic and sterilization laparoscopies appear to be safe, but
      more complex laparoscopies are associated with an unacceptably high number of
      serious complications requiring continuous follow-up and expertise.

PMID- 8990450
TI  - Transvaginal color Doppler sonography of the ureteral jets: a method to detect
      ureteral patency.
AB  - OBJECTIVE: To evaluate the feasibility of the detection of ureteral jets into the
      bladder in obstetric-gynecologic patients using transvaginal color Doppler
      ultrasound. METHODS: Fifty-two women were recruited and categorized into four
      groups: 1) 20 normal nonsurgical, 2) 17 post-cesarean delivery, 3) 12 post-total
      abdominal hysterectomy, and 4) three with only one functional kidney or ureter.
      In the first three groups, transvaginal color Doppler sonography was used to
      evaluate the time to detection of the first jet and the number of jets in 5
      minutes bilaterally. In the last group, the presence or absence of the jet was
      documented only on the functional side. Statistical analysis was performed using
      Student t test and analysis of variance followed by Tukey honestly significant
      difference. RESULTS: Urine jets could be detected bilaterally in all women except
      for those with only one functional kidney (accuracy 100%). Time to detection of
      the first jet did not differ significantly in the nonsurgical, cesarean, or
      hysterectomy patients on either the right side (P = .07) or the left side (P =
      .43). The total number of jets was similar in the nonsurgical and cesarean
      patients, but was significantly lower in the hysterectomy group (right side P =
      .006; left side P = .004). In the women with one functional kidney, the normal
      side was identified in all cases. CONCLUSION: Transvaginal color Doppler
      sonography is a simple, accurate technique that can be used to evaluate ureteral
      jets into the bladder in women. The length of time to detection of the first jet
      is not affected by the postoperative status. Fewer jets should be expected in
      women who have undergone hysterectomies. This method should be used when ureteral
      integrity is in question, especially after surgery.

PMID- 8990451
TI  - Methotrexate prophylaxis for persistent ectopic pregnancy after conservative
      treatment by salpingostomy.
AB  - OBJECTIVE: To investigate whether the incidence of persistent ectopic pregnancy
      after linear salpingostomy can be reduced by prophylactic administration of a
      single dose of methotrexate postoperatively. METHODS: Women who underwent linear
      salpingostomy for treatment of unruptured ectopic pregnancy and who agreed to
      participate in the study (n = 129) were randomly assigned to the prophylaxis or
      control group. Women with anemia, renal insufficiency, or liver disease were
      excluded. In the prophylaxis group, patients received a single dose of
      methotrexate, 1 mg/kg intramuscularly, within 24 hours postoperatively. No
      treatment was used in the control group. Both groups were followed with serial
      serum beta-hCG titers; titers were measured on the seventh postoperative day,
      then every 72 hours until levels were lower than 15 mIU/mL. A blood count and
      chemistry panel were also obtained on postoperative day 7, and any side effects
      related to methotrexate were noted. Persistent ectopic pregnancy was defined as a
      rise in the serum beta-hCG level or a decline of less than 20% between two
      consecutive measurements taken 3 days apart. RESULTS: A total of 116 women
      completed the postoperative follow-up: 54 in the prophylaxis group and 62 in the
      control group. Ten women had persistent ectopic pregnancy, one in the prophylaxis
      group (1.9%) and nine among the controls (14.5%); this difference was
      statistically significant (P < .05). The relative risk of developing persistent
      ectopic pregnancy after prophylactic methotrexate was 0.13 (95% confidence
      interval 0.02, 0.97). Three women (5.5%) reported mild side effects after
      methotrexate, but these resolved spontaneously. CONCLUSION: The incidence of
      persistent ectopic pregnancy was significantly reduced after a single
      prophylactic dose of systemic methotrexate administered postoperatively. This
      regimen is safe and can be used to decrease the extent of postoperative
      monitoring after conservative treatment of unruptured ectopic pregnancy.

PMID- 8990452
TI  - Cervical cytology in women with mental retardation.
AB  - OBJECTIVE: To examine our experience with performing pelvic examination and
      obtaining cervical cytology in women with mental retardation. METHODS: From
      November 1985 to October 1992, 658 women were seen in our clinic for women with
      mental disabilities. A standardized clinic visit form was completed for each
      woman. Of these records, 574 were available for analysis. All charts were
      reviewed for data on the level of retardation, incidence of sedation, success in
      performing pelvic examination and Papanicolaou smear, technique used for cervical
      smear, and pathology results of the cervical cytology. RESULTS: Of the 574 women,
      289 (50%) had severe, 69 (12%) moderate, and 31 (5%) mild retardation. In 185
      (32%), the exact level of retardation was not established. During the study
      period, 1235 pelvic examinations were analyzed. Within this group, 845
      examinations could be completed initially, 177 required the use of sedation
      (14%), and 213 (17%) examinations could not be completed. Of the 845
      examinations, 706 cervical smears were available for analysis. Of these, only 243
      (34%) contained endocervical cells. Two abnormal cytology results were found
      (0.3%). Of the 177 examinations done with sedation, 44 women (25%) still could
      not be examined. Cytology specimen results were obtained in 124 of the
      examinations, and 40 (32%) of these specimens contained endocervical cells. No
      cytologic abnormalities were present. In a cervical smear technique comparison,
      endocervical cells were present in 58% of 161 standard speculum examinations and
      in 18% of 93 cotton-swab tests (P < .001). CONCLUSION: Cytology specimens can be
      obtained without sedation in most mentally retarded women. Only one-third of
      Papanicolaou smears contained endocervical cells from examinations with sedation
      as well as those without. The cotton-swab technique has a significantly lower
      endocervical cell collection rate than the standard speculum technique. The
      incidence of abnormalities on cytologic examination appears to be low compared
      with other populations of women. Whether this is due to suboptimal smears, lower
      prevalence of human papillomavirus, or a combination of both remains to be
      resolved.

PMID- 8990453
TI  - A technique of minilaparotomy-assisted vaginal hysterectomy.
AB  - In minilaparotomy-assisted vaginal hysterectomy, the operation begins vaginally
      by opening the peritoneal folds and ligating the uterine vessels and uterosacral
      ligaments. Minilaparotomy is then performed for myomectomy, cutting the fallopian
      tubes and the utero-ovarian ligaments and detaching any adhesions on the anterior
      peritoneal angle. In 26 women who underwent this procedure, the feasibility rate
      was 100% and no intraoperative complications or postoperative morbidity was
      observed (except in one case of ovarian bleeding), indicating that vaginal
      hysterectomy assisted by minilaparotomy is a feasible approach for hysterectomy
      in the setting of large myomas, myomas with adhesions caused by endometriosis or
      previous pelvic surgery, and adenomyosis.

PMID- 8990454
TI  - An in-line suturing device to simplify sacrospinous vaginal vault suspension.
AB  - A disposable suturing instrument is used in our surgical method for sacrospinous
      vault suspension to facilitate suture placement and retrieval. The pararectal
      space is dissected and the suturing device is placed just medial to the lateral
      third of the sacrospinous ligament-coccygeus muscle complex. Depression of the
      device's firing button advances a standard needle in a controlled circular path
      through the sacrospinous ligament-coccygeus muscle complex. The needle is
      retrieved with a straight-needle holder at a consistent location, 3 mm from the
      shaft of the instrument. A second suture is placed 0.5-1 cm medial to the first
      suture. If the holding strength for either suture is considered inadequate, the
      device is reloaded with the same suture and subsequent bites are taken. The
      procedure is completed using standard methods. In ten women treated for vaginal
      vault eversion, lateral dissection was completed in less than 10 minutes, and
      passage of two sutures through the sacrospinous ligament was accomplished in less
      than 2 minutes. There were no complications. One patient described mild buttock
      pain that resolved in 1 week. At 4-6 months' follow-up, vaginal examination with
      maximal straining demonstrated direct apposition of the vaginal wall to the
      sacrospinous ligament.

PMID- 8990455
TI  - Supracervical hysterectomy: ... a time for reappraisal.
AB  - Supracervical or subtotal hysterectomy is a procedure that largely was discarded
      in the middle part of this century. This decision was made because of the
      reduction in morbidity and mortality associated with total hysterectomy, the only
      known and available method for the prevention of cervical cancer. This rationale,
      appropriate earlier in the century, has become somewhat undermined with the
      advent of Papanicolaou smear screening, colposcopic diagnosis, and simple
      outpatient therapy for preinvasive cervical neoplasia. Furthermore, some have
      argued that supracervical hysterectomy better preserves bladder and sexual
      function, and may be associated with reduced surgical and postoperative
      morbidity. Recently, laparoscopic supracervical hysterectomy has been introduced
      as another operative alternative with putative advantages over the procedure
      performed via laparotomy. However, for routine cases, the available literature
      does not confirm that one procedure is superior, regardless of the route of
      access. In selected cases, where benign conditions significantly distort the
      cervical anatomy complicating the dissection, supracervical hysterectomy would
      seem a prudent choice. It is clear that appropriately designed comparative
      studies are in order, to better determine the place for supracervical
      hysterectomy in the contemporary management of women with benign uterine disease.

PMID- 8990456
TI  - Permanent Erb palsy: a traction-related injury?
AB  - Historically, the primary risk factor attributed to brachial plexus injury during
      birth has been excessive traction applied at delivery to an entrapped anterior
      shoulder. However, recent evidence has suggested that not all cases of brachial
      plexus palsy are attributable to traction. We have encountered several cases of
      permanent Erb palsy associated with birth that were not attributable to traction
      applied at delivery. We reviewed cases of neonates with documented permanent Erb
      palsy that occurred either in the absence of shoulder dystocia or in the
      neonate's posterior arm in the presence of anterior shoulder dystocia. We
      identified four cases that occurred in the absence of shoulder dystocia and four
      cases that occurred in the posterior arm of infants with anterior shoulder
      dystocia. These data further support the notion that the etiology of permanent
      brachial plexus palsy associated with birth may not be related to traction.

PMID- 8990457
TI  - An approach to teaching ethical, legal, and psychosocial aspects of gynecologic
      oncology in a residency program.
AB  - An approach to teaching ethical, legal, and psychosocial issues in gynecologic
      oncology has been integrated into an obstetrics and gynecology residency program.
      Team-teaching is used, involving gynecologic oncology faculty members and a
      medical ethicist with experience teaching in the clinical setting of obstetrics
      and gynecology. The teaching takes place as part of ongoing teaching rounds in
      the division of gynecologic oncology. Articles from clinical journals are used to
      inform and stimulate discussion of clinical ethical, legal, and psychosocial
      issues. Integrating the teaching of ethical and legal aspects of gynecologic
      oncology into residency education is challenging, given the competing demands on
      the residents' time and the need for teaching to be clinically relevant. The
      program described in this article illustrates that such teaching can be carried
      out in a manner that covers main issues and has practical value for residents.

PMID- 8990458
TI  - Gene therapy and ovarian cancer: a review.
AB  - OBJECTIVE: To provide the obstetrician-gynecologist with the basic concepts of
      gene therapy, an overview of cancer gene therapy treatment strategies, and a
      summary of currently approved human gene therapy protocols for ovarian carcinoma.
      DATA SOURCES: A computerized search of articles published through December 1995
      was performed on the MEDLINE data base. Additional sources were identified
      through cross-referencing. METHODS OF STUDY SELECTION: All identified references
      were reviewed with particular attention to their relevance to gene therapy for
      ovarian cancer. TABULATION, INTEGRATION, AND RESULTS: Each reference was reviewed
      to determine the relevant contribution to the fundamental science of gene
      therapy. Particular attention was paid to those studies that offered a rational
      strategy that might contribute to therapy for ovarian malignancy. CONCLUSION:
      Advances in molecular biology, immunology, and virology have enabled the concept
      of gene therapy for neoplastic disorders to become a reality. Given the lack of
      effective conventional therapy, those patients with recurrent or refractory
      ovarian cancer should be considered for currently approved investigational gene
      therapy protocols.

PMID- 8990459
TI  - Excess males in preterm birth: interactions with gestational age, race, and
      multiple birth.

PMID- 8990460
TI  - Direct laparoscopic entry using a sharp and dull trocar technique.

PMID- 8990461
TI  - Measuring contraceptive effectiveness: a conceptual framework.

PMID- 8990462
TI  - [Recent progress in diagnosis of Cushing's disease].

PMID- 8990463
TI  - [Resection of glioma located in deep or eloquent area: application of functional
      mapping, intraoperative monitoring and navigation with CT or MRI-assisted
      stereotactic guidance].

PMID- 8990464
TI  - [Postoperative complications of anterior and middle skull base surgery].
AB  - The authors present the postoperative complications of skull base surgery based
      on a 10-year experience with 26 patients operated on via the supraorbital trans
      basal or orbitozygomatic approach. The lesions included 19 malignant tumors and
      seven benign tumors. Postoperative cerebrospinal (CSF) leak occurred in one of
      the two patients in whom the dural defects were repaired with a fascia lata
      graft. None of the remaining 24 patients who were repaired with a
      musculopericranial flap suffered postoperative CSF leak. Three patients developed
      epidural abscess, but no infection was seen in the patients who had been
      reconstructed with a vascularized musculo-cutaneous flap to occlude the dead
      space. Preoperative radiation therapy correlated with a high incidence of
      postoperative infection. Cranial nerve deterioration or palsy occurred in four
      patients. Intraoperative injury of the internal carotid artery occurred in one
      patient who developed severe neurological deterioration. After an average follow
      up period of 40 months (range 12 to 109 months), 68% of patients with malignant
      tumors and 100% of patients with benign tumors were alive with no evidence of
      recurrence.

PMID- 8990465
TI  - [Treatment of hydrocephalus without shunt placement: third ventriculostomy].
AB  - Hydrocephalus is usually treated by placing an extracranial CSF shunt. Endoscopic
      third ventriculostomy, however, has been revived recently as a less invasive
      method for treatment. We intended to avoid shunting or to eliminate the
      previously placed shunt with this procedure. The authors review their experiences
      on third ventriculostomy employing a flexible neuroendoscope under video
      monitoring in 14 cases of pediatric hydrocephalus. The result was that we
      succeeded in 11 cases (79%) by third ventriculostomy alone; we avoided shunting
      in 8 cases and eliminated a previously placed shunt in 3 cases. Clinical summary
      is shown on Table 1, and illustrative cases are presented with the figures and
      legend. The patients' group consisted of 8 males and 6 females. Their age ranged
      from 1 month to 17 years (average age, 6 yr) old. Background diseases of
      hydrocephalus were brain tumor in 6 cases, Chiari type I malformation in 3,
      intraventricular hemorrhage in 3, neonatal meningitis in 1 and arachnoid cyst in
      1 case. In the remaining 3 cases, however, we failed to avoid the necessity of
      placing shunt because of indirect reasons (recurrence of tumor, infection after
      another operation, subdural fluid collection). There was no major complication in
      relation to third ventriculostomy, except for a moderate elevation of temperature
      of several days' duration following the procedure. Indication and outcome of this
      operation is also discussed. Endoscopic third ventriculostomy is an efficacious
      procedure for the treatment of hydrocephalus in selected patients.

PMID- 8990467
TI  - [A case of jugular foramen neurinoma originating from glossopharyngeal nerve].
AB  - A 39-year-old man was admitted with right hearing loss, tinnitus and vertigo.
      Neurological examination on admission revealed right facial palsy, right acoustic
      nerve disturbance and cerebellar ataxia. CT scan demonstrated a mass with intra
      and extracranial extension in the pyramid bone concomitant with enlarged jugular
      foramen. MRI showed a ring-like enhanced, extra-axial mass in the right CP angle.
      Cerebral angiography showed no tumor stain. Venous phase of VAG revealed lateral
      displacement of the right sigmoidal sinus and obstruction of the internal jugular
      vein. Three dimensional CT was very useful to reveal enlarged jugular foramen.
      The tumor was resected totally and was approached through a right suboccipital
      craniectomy and mastoidectomy on July, 1994. Surgery confirmed that the tumor was
      a neurinoma originating from the glossopharyngeal nerve. After the operation,
      right facial palsy developed and transient fugitive CSF leakage was observed, but
      the patient is doing well. There was no amelioration of right hearing loss. JFN
      originating from the glossopharyngeal nerve is rare. Twenty-five cases of
      glossopharyngeal neurinoma are reviewed.

PMID- 8990466
TI  - [Detection of microemboli in patients with extracranial carotid artery stenosis
      by transcranial Doppler sonography].
AB  - Embolism from a stenotic lesion of the extracranial internal carotid artery (ICS)
      is considered to be an important pathomechanism of cerebral infarction. The
      purpose of this study is to estimate the risk of cerebral infarction associated
      with microembolism in patients with ICS and thereby to determine the importance
      of TCD-detected microemboli in this condition. Seventy-one cases with more than
      30% ICS and 10 cases without ICS were studied. TCD monitoring was carried out for
      an hour at the ipsilateral middle cerebral artery of each case using a 2-MHz
      pulse-wave transcranial Doppler device. High intensity transient signals were
      counted as microemboli. Microemboli were detected in 27 of 71 cases with ICS, but
      not in cases without ICS. Microemboli were detected more frequently in cases with
      70% to 99% ICS (53.3%) compared with in cases with 30% to 69% ICS (12.5%).
      Cerebral infarctions were recognized in the ipsilateral hemisphere in 23 of 27
      cases with microemboli (85.2%) by means of MRI. In contrast, cerebral infarctions
      were recognized only in 21 of 45 cases without microemboli (47.7%). These results
      suggest that a stenotic lesion of the extracranial internal carotid artery,
      especially high-grade stenosis, is a major source of cerebral embolism and that
      detection of microemboli by TCD is a useful tool capable of reliably assessing
      the risk of cerebral infarction due to ICS.

PMID- 8990468
TI  - [Effect of factor XIII on intractable CSF leakage after a transpetrosal-approach
      operation: a case report].
AB  - The authors reported an experience showing that the XIII factor was effective for
      intractable cerebrospinal fluid (CSF) leakage after a transpetrosal operation to
      deal with cerebellopontine angle meningioma. A 63-year-old female noted a slight
      headache and a floating feeling. She became dependent on a stick for walking
      alone because of gradual gait disturbance. As the headache became more severe,
      she consulted the outpatient clinic of the department of neurosurgery of Kobe
      University Hospital. Magnetic resonance images (MRI) revealed a 4.3 x 3.0cm sized
      right cerebellopontine angle tumor. She was admitted for the purpose of removal
      of the tumor and preoperative examinations were performed. Neurological findings
      on admission showed only slight right cerebellar signs. The operation was
      performed via the transpetrosal approach and the tumor was totally removed
      (Simpson Grade II). It took 12 hours 40 minutes for the operation. The amount of
      blood loss was 1970ml and the blood transfusion volume was 1200ml. Postoperative
      course was uneventful and her complaints disappeared. There were no postoperative
      complications at all, but 2 weeks after the operation, CSF leakage under the skin
      flap appeared. As subcutaneous fluid collection after skull base surgery is
      usual, spinal drainage and compression of the skin flap was carried out but these
      measures were not effective. The collection of fluid did not disappear for 2
      weeks. Based on our successful experience with the XIII factor therapy in
      intractable cerebrospinal fluid leakage from the nose after a transsphenoidal
      approach operation for recurrent pituitary adenoma, the blood level of the XIII
      factor activity was examined. As the result was far below the normal limit in
      this case, the XIII factor was infused at a rate of 750 units per day for 5 days.
      One week after the administration, the level of the XIII factor became normal.
      Fluid collection disappeared and the drainage tube was removed. Recently, in
      neurosurgery, skull base surgery has been used widely and the range of craniotomy
      has been extended because operations can now be performed without compression of
      cerebral cortexes. However, operation time has increased and the volumes of
      bleeding and of blood transfusion are increasing. Postoperative complications
      such as CSF leakage and infection have become new problems. In this case, the
      XIII factor was still far below the normal level 2 weeks after the operation and
      it could be considered to have caused delayed CSF leakage. Some papers have
      reported that the XIII factor was effective in treating intractable fistula after
      operations in other surgical areas. However, this is the first report of skull
      base surgery such as an operation using transpetrosal approach taking advantage
      of the effect of the XIII factor.

PMID- 8990469
TI  - [Usefulness of the interlocking detachable coil for the repeatedly ruptured
      dissecting aneurysm of the vertebral artery in the acute stage].
AB  - A 44-year-old male with a repeatedly ruptured dissecting aneurysm of the
      vertebral artery (VA) manifesting with subarachnoid hemorrhage was successfully
      treated with endovascular surgery using an interlocking detachable coil (IDC). He
      had a dissecting aneurysm in the left VA distal to the left posterior inferior
      cerebellar artery (PICA). Because the dissecting aneurysm ruptured repeatedly and
      his clinical condition was moribund, direct surgery was not indicated. The
      dissecting aneurysm was embolized with an IDC and additional platinum coils.
      Among patients with a ruptured VA dissecting aneurysm, proximal occlusion is
      generally indicated. But the direct embolization of a dissecting aneurysm can be
      applied in cases in which the aneurysm is ruptured repeatedly in the acute stage.
      IDC is a useful and safe material for endovascular surgery of a ruptured VA
      dissecting aneurysm.

PMID- 8990470
TI  - [Transient mutism after resection of left frontal lobe astrocytoma in adult: case
      report].
AB  - We reported a case of a 32-year-old female who had a transient mutism after
      resection of a malignant astrocytoma in the left frontal lobe. Preoperatively
      magnetic resonance (MR) imaging revealed a cystic tumor in the left frontal lobe.
      The patient underwent surgery. She was alert but did not speak immediately after
      surgery. She could follow verbal commands, comprehend written language, and write
      letters. She had no cranial nerve or extremity paresis. Seven days
      postoperatively, she began to say simple words, and one month postoperatively she
      could talk normally. Postoperative MR imaging revealed a hypointensity area on T1
      weighted image in the frontal lobe including a part of the anterior cingulate
      cortex and the anterior part of the corpus callosum. It appears that a dominant
      hemisphere lesion of both the anterior cingulate cortex and the corpus callosum
      may be responsible for the development of postoperative mutism.

PMID- 8990471
TI  - [A case of spontaneous cervical internal carotid artery dissection].
AB  - Dissection of the extracranial carotid artery is a recognized cause of ischemia,
      particularly in young persons who present with acute neurologic deficits, both
      transient and permanent. We describe a patient with a spontaneous dissection of
      the cervical internal carotid artery (ICA). A previously healthy 24-year-old man
      was hospitalized because of a sudden onset of right hemiparesis and consciousness
      disturbance. In reality, right cervical pain preceded this attack. The first
      brain MRI revealed a cerebral infarction in the right cerebral hemisphere
      including basal ganglia. A conventional angiography was performed 1 week later.
      The following angiographic picture was considered to be consistent with the
      diagnosis of cervical artery dissection: gradually tapered occlusion beginning
      distal to the carotid bifurcation. And MRA revealed the same finding. A cervical
      MRI revealed as an eccentric signal void (corresponding to the residual lumen)
      surrounded by a semilunar hyperintensity (corresponding to the mural hematoma) on
      T1- and T2-weighted images. Dynamic CT scan (D-CT) revealed an eccentric and
      crescent contrast enhancement (corresponding to the residual lumen) surrounded by
      a relative hypodensity compared with muscle (corresponding to the mural
      hematoma), itself surrounded by a thin annular enhancement. From these results,
      we diagnosed this patient with ICA occlusion for dissection of the extracranial
      carotid artery. But we decided this case contraindication of anastomosis because
      he had had a major stroke. Our findings suggest that MRA, cervical MRI and DCT
      provide early recognition of internal carotid artery dissection and monitoring of
      its resolution. Thus, these studies may guide clinical decisions according to the
      development of the dissection.

PMID- 8990472
TI  - [A chronic encapsulated expanding hematoma with cyst formation caused by rupture
      of arteriovenous malformation: a case report].
AB  - A 57-year-old male was admitted to our hospital complaining of a headache with
      disturbance of consciousness on November 7, 1994. CT scans revealed an
      intracerebral hematoma of 25ml in volume in the left frontal lobe with adjacent
      spotty calcification. An arteriovenous malformation (AVM) with a nidus of 2.0 x
      2.0cm in size was found to be the cause of the hematoma by cerebral angiography.
      Since the patient complained of mild right hemiparesis 10 days after the onset,
      CT scans were taken and a slightly enlarged hematoma with capsule formation was
      observed. On the 31st day after the onset, the hematoma had liquefied and the
      surrounding capsule was clearly visible on CT. Since the patient's only symptom
      was a slight headache, and he displayed no other serious conditions, a palliative
      operation was planned. The AVM was removed and the capsule was resected 41 days
      after the onset. The capsule or cyst wall of the liquefied hematoma was composed
      of three layers: a granulation layer with a neovascular system on the inside, a
      collagenous layer in the middle, and a reactive brain tissue layer on the
      outside. The structure of the capsule was the same as the structure of the cyst
      wall in chronic hematomas that have been reported as cystic AVM or encapsulated
      expanding hematoma in the literature. We would therefore like to propose that
      chronic encapsulated expanding hematomas form with time due to intermittent
      bleeding or exudation form the neovascular system of a cyst wall.

PMID- 8990473
TI  - [A case of adult moyamoya disease showing fulminant clinical course associated
      with progression from unilateral to bilateral involvement].
AB  - We reported a case of adult moyamoya disease showing acute deterioration in which
      a unilateral occlusive lesion progressed to bilateral involvement during a period
      of 49 months. A 54-year-old male suffered from progressive weakness in his right
      extremities and disturbance of speech. On admission, neurological examination
      demonstrated mild right hemiparesis with global aphasia. A computed tomography
      (CT) scan showed a strange low density area in the territory of the left ACA and
      frontal branches of the left MCA. Left carotid angiography showed stenosis of the
      ICA at the terminal portion, occlusion of the ACA and MCA at each origin, and
      basal moyamoya vessels. Right carotid angiography demonstrated no occlusive
      lesions except for the general narrowing of the right ACA, without moyamoya
      vessels. This case was classified as adult-onset "probable" moyamoya disease
      according to the diagnostic criteria of the Japan Cooperative Research Committee.
      Left superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis was
      performed. The patient showed gradual amelioration of neurological symptoms, and
      was discharged on foot with mild motor aphasia. However, 4 years later he
      complained of weakness in his left lower extremity. A second cerebral
      angiography, performed 49 months after the initial angiography demonstrated
      severe stenosis of the left ICA at the terminal portion progressing in the
      proximal direction with decreasing basal moyamoya vessels, while severe stenosis
      extended from the terminal portion of the right ICA to the M1 portion with newly
      developed moyamoya vessels in the right basal area. At this time, we considered
      that this case was a definite case of moyamoya disease. The second cerebral
      angiography was completed uneventfully. However, the patient then suddenly showed
      acute deterioration 5 hours after the angiography. Emergent cerebral angiography
      disclosed an occlusion of the right ICA at the terminal portion. Thereafter he
      showed acute deterioration in consciousness. A CT scan at the time revealed a
      huge low density area in the territory of the right ACA and MCA. We performed
      emergent external decompression, but he did not recover from the sequelae of
      cerebral infarction and died 3 days later. This rare case suggested the
      possibility of progression to bilateral involvement although it was a case of
      adult-onset "probable" moyamoya disease. We consider that acute ischemic
      deterioration should be kept in mind especially in aged cases of adult-onset
      moyamoya disease. Careful observation should be performed by the serial MR
      angiography in adults with "probable" moyamoya disease even though they are
      clinically asymptomatic.

PMID- 8990474
TI  - [Saccular aneurysm-like bleb formation after rupture of the internal carotid
      posterior communicating artery aneurysm: a case with interesting angiographic
      findings].
AB  - A case of saccular aneurysm-like bleb formation after rupture of an aneurysm in
      the internal carotid-posterior communicating artery. In connection with this, an
      interesting angiographic finding was reported. A 65-year-old man suffered from
      sudden disturbance of consciousness and left hemiparesis. Computed tomography
      (CT) scan revealed typical subarachnoid hemorrhage localized in the right Sylvian
      fissure. Next day, a cerebral angiography was performed, but no aneurysm was
      detected. A second angiography was performed 21 days after the onset, and it
      revealed a saccular right internal carotid-posterior communicating artery (IC-PC)
      aneurysm. An operation for the IC-PC aneurysm was performed by conventional
      pterional approach. However, intraoperative findings were unexpected. The
      collapsed ruptured true IC-PC aneurysm was found at the orifice of the larger
      bleb, and the ruptured point was in the neck of the true aneurysm. Clipping of
      the aneurysm was performed successfully. The patient was discharged on foot. The
      aneurysm detected by the second angiography was not a true one but a bleb
      formation. Continuous hemodynamic stress on the rupture point may induce the
      formation of such an aneurysm-like bleb. It should be kept in mind that an
      aneurysm found in the chronic period might be an aneurysm-like bleb.

PMID- 8990475
TI  - [Protection of excitotoxicity].

PMID- 8990476
TI  - [Neurotrophic factors: neuronal death and its protection].

PMID- 8990477
TI  - [Free radical scavengers].

PMID- 8990478
TI  - [C-type hepatitis in spontaneous intracerebral hemorrhage].
AB  - The prevalence of hepatitis C virus (HCV) in 139 cases of spontaneous
      intracerebral hemorrhage (ICH) was investigated with regard to a diagnosis of
      hypertension. Patients under 30 and over 79 years of age were omitted from this
      study, and those with complicating malignancies and undergoing anti-coagulation
      or antiplatelet therapy were also excluded. The prevalence of HCV was
      significantly higher among the ICH group as a whole (19 out of 139 cases, p <
      0.05) especially in the non-hypertensive group (7 out of 29 cases, p < 0.01),
      compared to the control group (7 out of 140 cases without ICH). The non
      hypertensive HCV-positive group (7 cases) had significantly higher GOT and GPT
      levels, prolonged PT and a-PTT values, and lower platelet counts, compared to the
      hypertensive HCV-negative group (74 cases). The HCV antibody titers did not
      differ among the HCV-positive groups. The results suggest that chronic hepatitis
      due to HCV infection is a major risk factor for spontaneous intracerebral
      hemorrhage, especially in non-hypertensive patients.

PMID- 8990479
TI  - [Super selective amytal test for functional evaluation of the brain--a less
      invasive functional test].
AB  - In the neurosurgical field, it is very important to evaluate localized function
      of the affected region preoperatively. In order to investigate lateralized and
      localized brain function, we have developed an alternative to the original Wada
      test, and refer to it as the super selective amytal test (SSAT). We performed
      super selective catheterization of the target artery after conventional carotid
      angiography, injected Amytal (amobarbital, 30-100 mg) through a micro-catheter,
      and identified potential local function. In ten cases, including AVM, aneurysm,
      and brain tumor, we investigated localized function of the affected site
      preoperatively by SSAT, and chose our treatment based on the results of this
      test. There was a good correlation between the results of the SSAT and the
      results of surgery in every case. There were no prolonged neurological
      complications of this test. Evaluation of the results of the SSAT should be
      interpreted under precise DSA control, since blood flow in the brain differ among
      individuals. This test may contribute to our knowledge of localized function in
      the cerebral cortex and deep brain areas in neurosurgical patients.

PMID- 8990480
TI  - [Idiopathic intracranial hypotension associated with decreased blood
      concentration of vitamin A].
AB  - We report a case of idiopathic intracranial hypotension, a clinically rare
      syndrome. A 28-year-old woman was admitted with orthostatic headaches associated
      with nausea secondary to intracranial hypotension. Lumbar puncture yielded an
      opening pressure of 4 cmH2O in the lateral recumbent position, and the spinal
      fluid protein concentration was 56 mg/dl. There was no history of lumbar puncture
      or clear history of head trauma before the onset of symptoms. Spinal and cranial
      MRI showed no evidence of CSF leakage, and there was diffuse meningeal
      enhancement following gadolinium infusion. Cranial MRI showed no evidence of
      brain displacement due to low CSF pressure, such as tonsillar herniation.
      Radioisotope cisternography (RIC) showed rapid accumulation of isotope within the
      bladder and early disappearance of radioactivity from the head. About 2 months
      later the headaches resolved spontaneously, and repeated lumbar puncture yielded
      opening pressure elevation to 10.5 cmH2O with a decrease in protein concentration
      to 28 mg/dl. The abnormal MRI and RIC findings had become normal. On the other
      hand, the patient had a low blood concentration of vitamin A, which is thought to
      play some role in the production of CSF. The results of RIC suggested that the
      patient may have become symptomatic because of undetectable CSF leakage or
      hyperabsorption, but diminished production of CSF due to lower blood vitamin A
      concentrations may also have been a factor predisposing to this syndrome.

PMID- 8990481
TI  - [A case of psittacosis with psychiatric symptoms, abnormal EEG, and abnormal
      SPECT].
AB  - A 40-year-old woman was admitted to our hospital with disorientation, delusional
      idea, and sensory disturbance of lower face after having a fever and cough for 5
      days. A chest X-ray examination revealed an infiltration in the left lower lobe
      field. Psittacosis was diagnosed because the serum antibody titer against
      chlamydia psittaci was elevated. Electroencephalogram showed right temporal lobe
      spikes. SPECT showed decreased accumulation of 99mTc-HMPAO in the right frontal
      and temporal lobe. Computed tomography scan of the brain was normal. This patient
      was diagnosed as ornithsis Encephalitis.

PMID- 8990482
TI  - [Recurrent aseptic meningitis caused by rupture of a pineal cyst].
AB  - A 40-year-old woman experienced three attacks of aseptic meningitis in 19 months.
      Each attack was characterized by sudden onset of meningeal irritation followed by
      spontaneous remission in several days. The patient was free of neurological
      symptoms between the attacks. In the acute phase of each attack, her
      cerebrospinal fluid (CSF) showed mononuclear pleocytosis and increased protein
      concentration. Epithelial cell clusters in the CSF were evident during the third
      episode. No pathogenic microorganisms were identified in CSF or blood cultures.
      Brain imaging revealed a pineal cyst, 1 cm in diameter, and we suspected that the
      epithelial cell clusters represented the ruptured cystic wall and that the
      recurrent aseptic meningitis was triggered by spontaneous rupture of the cyst.
      Recently several new etiologies for the benign recurrent aseptic meningitis
      (Mollaret's meningitis) have been reported, but its existence as a clinical
      entity is still in dispute. Our case appears to support "spontaneous rupture of
      central nervous system epidermoid cysts" as one of the etiologies of recurrent
      aseptic meningitis.

PMID- 8990483
TI  - [Magnetic resonance imaging in thiamine responsive pyruvate dehydrogenase complex
      deficiency].

PMID- 8990485
TI  - Differential coupling of m1, m3, and m5 muscarinic receptors to activation of
      neuronal nitric oxide synthase.
AB  - The selectivity of coupling of m1, m3, and m5 muscarinic receptors to activation
      of the neuronal type of nitric oxide synthase was investigated. Stimulation with
      the agonist carbachol of all three receptor subtypes expressed in Chinese hamster
      ovary cells resulted in a rapid and transient activation of the enzyme, as
      measured by stimulation of guanylate cyclase in reporter neuroblastoma cells.
      Carbachol was more potent and efficacious at m5 receptors than at the other two
      receptor subtypes. Stimulation of all three muscarinic receptors resulted in an
      increased concentration of intracellular calcium, with a time course that
      preceded activation of nitric oxide synthase. At each receptor subtype, there was
      a close relationship between the magnitude of the maximal calcium response and
      that of enzyme activation.

PMID- 8990484
TI  - [A 91-year-old man with a stroke, hypertension, and renal failure].
AB  - We report a 91-year-old man who had a stroke and died of renal failure. He had
      been treated for hypertension since 20 years before the onset of the present
      illness. In addition, he was operated on a gastric cancer 17 years previously.
      Otherwise he was doing well until May 29, 1991 (when he was 87-year-old) when he
      had sudden onset of dysarthria and right facial weakness. He was admitted to our
      hospital. On admission, general physical examination was unremarkable, and
      neurologic examination revealed a mentally sound man with slight dysarthria,
      right facial weakness, orolingual dyskinesia, and dysequilibrium in which he
      showed difficulty in tandem gait; however, no cerebellar ataxia was noted. A
      cranial CT scan revealed leukoaraiosis with multiple low density areas in the
      cerebral white matter. His BUN was 37 mg/dl and Cr 2.2 mg/dl. His neurologic
      symptoms cleared within the next few weeks and he was discharged with ticlopidine
      100 mg q.d.. He had been doing well after the discharge except for gradual
      worsening of his renal function; his BUN was 65 mg/dl and Cr 3.27 mg/dl in April
      of 1994. On March 10, 1995, he fell down and hit his back; he became unable to
      walk because of pain, and he was admitted again on March 16, 1995. On admission,
      his blood pressure was 170/80 mmHg. There was an 1 + pitting pretibial edema;
      otherwise general physical examination was unremarkable. Neurologic examination
      revealed an alert and oriented man, however, Hasegawa's dementia scale was 23/30.
      Higher cerebral functions as well as cranial nerves were intact. He showed some
      unsteadiness of gait, however, no motor weakness or ataxia was noted. Deep tendon
      reflexes were diminished, but Chaddock sign was positive bilaterally. Vibration
      was diminished in the feet, however, pain and touch sensations were intact.
      Laboratory examination revealed a compression fracture of the twelfth thoracic
      vertebra. Blood count and chemistries were as follows; Hb 7.6 g/dl, Hct 23.3%, TP
      6.0 g/dl, Alb 3.6 g/dl, BUN 87 mg/dl, Cr 4.53 mg/dl, T-Chol 174 mg/dl, HDL-Chol
      49 mg/dl, Glu 156 mg/dl, Na 142 mEq/L, K 5.4 mEq/L, Cl 115 mEq/L. A urine
      specimen contained 1 + protein and 1 + glucose, and the sediments contained
      hyaline casts. A cranial CT scan was essentially same as that taken four years
      ago. His hospital course was complicated with pneumonia, congestive heart
      failure, and progressive renal failure. He was treated with intravenous fluid,
      chemotherapy, and other supportive measures, however, he expired from respiratory
      failure on April 30, 1995. He was discussed in a neurologic CPC, and the chief
      discussant arrived at the conclusion that the patient had Binswanger's disease in
      the brain, benign nephrosclerosis from arteriolosclerosis due to hypertension,
      congestive heart failure, and pneumonia. Opinions were divided regarding the
      question as to whether or not this patient had Binswanger's disease. Although his
      cranial CT scan revealed leukoaraiosis, his dementia and gait disturbance was
      only mild until his fall on March, 1995. Clinical features did not conform to
      those of Binswanger's disease. Postmortem examination of the right hemisphere
      revealed wide spread atherosclerosis and arteriolosclerosis. The kidney showed
      benign nephrosclerosis due to arteriolosclerosis. Sclerotic changes were also
      seen in the coronary arteries and the left middle cerebral artery with 70%
      stenosis. Myelin stain showed diffuse myelin pallor of the cerebral white matters
      with scattered small infarcts. Arterioles in the white matter showed
      arteriolosclerosis. Small infarcts were also seen in the putamen and in the
      thalamus. This patient appeared to have had circulatory disturbance of the white
      matter which is the basic abnormality causing Binswanger's disease. However,
      white matter changes in this patient were not quite severe enough to make a
      pathologic diagnosis of Binswanger's disease.

PMID- 8990486
TI  - On a dual role for clonidine stimulation of the ventromedial nucleus of the
      hypothalamus in sodium and potassium renal excretions of rats.
AB  - The effects of clonidine on sodium and potassium excretions were examined after
      previous administration of prazosin (an alpha 1-adrenergic receptor antagonist)
      and yohimbine (an alpha 2-adrenergic receptor antagonist) into the ventromedial
      nucleus of the hypothalamus of conscious rats. Clonidine injected into the
      ventromedial nucleus of the hypothalamus induced inhibitory and facilitatory
      effects on the urinary sodium and potassium excretions. The results suggest that
      facilitatory effects of clonidine on natriuresis and kaliuresis are mediated
      through activation of alpha 1-adrenoceptors and that inhibitory effects require
      alpha 2A-adrenoceptors.

PMID- 8990487
TI  - Relaxant responses by optical isomers of ephedrine and methylephedrine in guinea
      pig tracheal smooth muscle.
AB  - The effects of optical isomers of ephedrine and methylephedrine on the guinea pig
      tracheal smooth muscle were studied. l-Ephedrine markedly caused a graded
      relaxation of the guinea pig trachea where the tone had been raised
      spontaneously. A rightward shift of the l-ephedrine concentration-response curve
      was observed for propranolol and butoxamine, and the pA2 values for propranolol
      and butoxamine were 8.55 and 6.38, respectively. d-Methylephedrine markedly
      caused a graded relaxation of the guinea pig trachea contracted with histamine.
      Propranolol and bupranolol did not affect the relaxant response to d
      methylephedrine. d-Methylephedrine competitively antagonized the contractile
      responses to histamine, and the pA2 value for d-methylephedrine was 5.12. These
      results suggest that l-ephedrine-induced relaxation of the guinea pig trachea is
      mediated through beta 2-adrenoceptors, whereas d-methylephedrine relaxes the
      guinea pig trachea by blocking histamine receptors.

PMID- 8990488
TI  - Role of cyclic nucleotides in contraction induced by oxytocin in the testicular
      capsule of the rat in vitro.
AB  - The effects of phosphodiesterase inhibitors, an activator and an inhibitor of
      guanylyl cyclase, and cAMP and cGMP analogs on oxytocin-induced contractions have
      been studied in the testicular capsule of rats. The nonspecific phosphodiesterase
      inhibitors, theophylline and caffeine, attenuated the oxytocin-induced
      contractions via mechanisms that seem to be related to an increase in cAMP
      levels, since a similar effect was produced by dibutyryl cAMP. Sodium
      nitroprusside facilitated oxytocin-induced contractions. This effect was mimicked
      by dibutyryl cGMP. Methylene blue, an inhibitor of soluble guanylyl cyclase,
      decreased oxytocin-induced contractions, which suggests an involvement of
      guanylyl cyclase in the oxytocin effect. These results suggest that cAMP
      modulates the contraction and that cGMP, contrary to what happens in most smooth
      muscles, could participate in oxytocin-induced contractions in the testicular
      capsule of rats.

PMID- 8990489
TI  - Canine retinal arterial and arteriolar dilatation induced by nipradilol, a
      possible glaucoma therapeutic.
AB  - The effects of nipradilol, an ocular hypotensive drug, on isolated canine retinal
      central arteries and on retinal arterioles in vivo were investigated. Nipradilol
      (10(-9) to 10(-5) mol/l) produced a dose-related relaxation of the arterial
      strips contracted with prostaglandin F2 alpha which was not influenced by timolol
      or indometacin. The median effective concentration of this drug was five times
      that of glycerol trinitrate (GTN). The nipradilol-induced relaxation in the
      endothelium-intact strips was not influenced by NG-nitro-L-arginine, a nitric
      oxide synthase inhibitor, but was abolished by oxyhemoglobin and methylene blue.
      Treatment with high concentrations of sodium nitroprusside abolished the response
      to nipradilol, as observed with that to GTN. Retinal arterial strips responded to
      isoproterenol with a slight relaxation which was depressed by nipradilol. In
      anesthetized dogs, intra-arterial injections of nipradilol dilated the retinal
      arterioles in the ocular fundus; the dilator potency was approximately one fifth
      that of GTN. It is concluded that nipradilol dilates canine retinal arteries in
      vitro and arterioles in vivo, possibly due to activation of soluble guanylate
      cyclase and increased production of cyclic guanosine monophosphate that are
      associated with nitric oxide liberated from the molecule itself in the tissue but
      not derived from the endothelium and perivascular nerve. Beta adrenoceptor
      blocking action was determined in the retinal artery.

PMID- 8990490
TI  - Increase of adenosine release by adenosine antagonists in hearts with coronary
      occlusion and reperfusion.
AB  - In isolated perfused rat hearts with coronary occlusion and reperfusion, the
      effect of adenosine antagonists on the release of adenosine and its degradation
      products inosine, hypoxanthine, xanthine and uric acid was investigated. An
      antagonist with high selectivity for the A1 receptor, 8-phenyltheophylline, was
      applied and compared with the relatively unspecific antagonist theophylline, used
      in its water-soluble form aminophylline. Depending on the duration of coronary
      occlusion, more or less severe tachyarrhythmias occurred during the myocardial
      ischemia, and particularly during the subsequent coronary reperfusion. Large
      amounts of the nucleosides and oxypurines were released after reopening the
      coronary artery. The release was particularly, high in hearts with ventricular
      fibrillation. Both adenosine antagonists increased the release in a highly
      significant way. The findings let assume that adenosine has perhaps a modulating
      effect on its own release, which can be blocked by adenosine antagonists.

PMID- 8990491
TI  - Physiological effects of a novel bioactive agent.
AB  - Urinary bladder smooth muscle contraction can be evaluated using field
      stimulation (neurohumoral transmission), carbachol (muscarinic stimulation), and
      KCl (direct membrane depolarization). We recently evaluated the activity of a
      novel organic chemical, macrocycle-1, on the contractile responses of the bladder
      to field stimulation, carbachol, and KCl. Isolated strips of rabbit bladder were
      mounted in individual baths containing 7.5 ml Tyrode's solution. The response to
      FS (1-32 Hz), carbachol (1 mumol/l), and KCl (120 mmol/l) were determined in the
      presence and absence of 3 different concentrations of macrocycle-1. Maximal
      tension, the rate of tension generation, the time to maximal tension, and the
      rate of decay following maximal tension were determined. The results can be
      summarized as follows: (1) In the absence of macrocycle-1, maximal tension and
      the maximal and mean rate of tension generation increased with frequency, whereas
      the time to maximal tension was constant. The rate of decay of tension following
      maximum tension was greater for 8, 16 and 32 Hz as compared to 1 or 2 Hz. (2) The
      maximal response to KCl was lower than either FS or carbachol. The maximal rates
      of tension generation for carbachol and KCl were lower than that of FS; and the
      rate of tension generation for KCl was lower than that of carbachol. The time to
      maximal stimulation for KCl was greater than that of either carbachol or FS. (3)
      Macrocycle-1 had a greater inhibitory effect on KCl stimulation than on carbachol
      stimulation; and a greater inhibitory effect on KCl and carbachol stimulation
      than on FS. (4) The rate of tension generation was more sensitive to macrocycle-1
      inhibition than was the maximal tension responses to all methods of stimulation.
      Our current hypothesis is that macrocycle-1 is acting as an intracellular calcium
      buffer whose affinity constant and association rate does not interfere with rapid
      intracellular release mechanisms (FS) while it inhibits slow intracellular
      calcium release mechanisms (carbachol and KCl).

PMID- 8990492
TI  - PCPA increases aggression in male firemouth cichlids.
AB  - We observed the effect of the 5-hydroxytryptamine synthesis inhibitor p
      chlorophenylalanine on aggression in male firemouth cichlids (Cichlasoma meeki).
      p-Chlorophenylalanine-treated firemouths showed a significantly greater number of
      mirror-directed bites as compared with saline-injected controls. This finding is
      consistent with the effects of this drug on social aggression in mammals and
      birds and supplements previous reports that 5-hydroxytryptamine inhibits
      aggression in fish.

PMID- 8990493
TI  - Positioning hydrogen atoms by optimizing hydrogen-bond networks in protein
      structures.
AB  - A method is presented that positions polar hydrogen atoms in protein structures
      by optimizing the total hydrogen bond energy. For this goal, an empirical
      hydrogen bond force field was derived from small molecule crystal structures.
      Bifurcated hydrogen bonds are taken into account. The procedure also predicts
      ionization states of His, Asp, and Glu residues. During optimization, side-chain
      conformations of His, Gln, and Asn residues are allowed to change their last chi
      angle by 180 degrees to compensate for crystallographic misassignments. Crystal
      structure symmetry is taken into account where appropriate. The results can have
      significant implications for molecular dynamics simulations, protein engineering,
      and docking studies. The largest impact, however, is in protein structure
      verification: over 85% of protein structures tested can be improved by using our
      procedure.

PMID- 8990494
TI  - Spectroscopic evidence for preexisting T- and R-state insulin hexamer
      conformations.
AB  - The insulin hexamer is an allosteric protein exhibiting both positive and
      negative cooperative homotropic interactions and positive cooperative
      heterotropic interactions (C. R. Bloom et al., J. Mol. Biol. 245, 324-330, 1995).
      In this study, detailed spectroscopic analyses of the UV/Vis absorbance spectra
      of the Co(II)-substituted human insulin hexamer and the 1H NMR spectra of the
      Zn(II)-substituted hexamer have been carried out under a variety of ligation
      conditions to test the applicability of the sequential (KNF) and the half-site
      reactivity (SMB) models for allostery. Through spectral decomposition of the
      characteristic d-->d transitions of the octahedral Co(II)-T-state and tetrahedral
      Co(II)-R-state species, and analysis of the 1H NMR spectra of T- and R-state
      species, these studies establish the presence of preexisting T- and R-state
      protein conformations in the absence of ligands for the phenolic pockets. The
      demonstration of preexisting R-state species with unoccupied sites is
      incompatible with the principles upon which the KNF model is based. However, the
      SMB model requires preexisting T- and R-states. This feature, and the symmetry
      constraints of the SMB model make it appropriate for describing the allosteric
      properties of the insulin hexamer.

PMID- 8990495
TI  - Protein fold recognition and dynamics in the space of contact maps.
AB  - We introduce an energy function for contact maps of proteins. In addition to the
      standard term, that takes into account pair-wise interactions between amino
      acids, our potential contains a new hydrophobic energy term. Parameters of the
      energy function were obtained from a statistical analysis of the contact maps of
      known structures. The quality of our energy function was tested extensively in a
      variety of ways. In particular, fold recognition experiments revealed that for a
      fixed sequence the native map is identified correctly in an overwhelming majority
      of the cases tested. We succeeded in identifying the structure of some proteins
      that are known to pose difficulties for such tests (BPTI, spectrin, and cro
      protein). In addition, many known pairs of homologous structures were correctly
      identified, even when the two sequences had relatively low sequence homology. We
      also introduced a dynamic Monte Carlo procedure in the space of contact maps,
      taking topological and polymeric constraints into account by restrictive dynamic
      rules. Various aspects of protein dynamics, including high-temperature melting
      and refolding, were simulated. Perspectives of application of the energy function
      and the method for structure checking and fold prediction are discussed.

PMID- 8990496
TI  - Factors governing the foldability of proteins.
AB  - We use a three-dimensional lattice model of proteins to investigate
      systematically the global properties of the polypeptide chains that determine the
      folding to the native conformation starting from an ensemble of denatured
      conformations. In the coarse-grained description, the polypeptide chain is
      modeled as a heteropolymer consisting of N beads confined to the vertices of a
      simple cubic lattice. The interactions between the beads are taken from a random
      gaussian distribution of energies, with a mean value B0 < 0 that corresponds to
      the overall average hydrophobic interaction energy. We studied 56 sequences all
      with a unique ground state (native conformation) covering two values of N (15 and
      27) and two values of B0. The smaller value of magnitude of B0 was chosen so that
      the average fraction of hydrophobic residues corresponds to that found in natural
      proteins. The higher value of magnitude of B0 was selected with the expectation
      that only the fully compact conformations would contribute to the thermodynamic
      behavior. For N = 15 the entire conformation space (compact as well as noncompact
      structures) can be exhaustively enumerated so that the thermodynamic properties
      can be exactly computed at all temperatures. The thermodynamic properties for the
      27-mer chain were calculated using the slow cooling technique together with
      standard Monte Carlo simulations. The kinetics of approach to the native state
      for all the sequences was obtained using Monte Carlo simulations. For all
      sequences we find that there are two intrinsic characteristic temperatures,
      namely, T theta and Tf. At the temperature T theta the polypeptide chain makes a
      transition to a collapsed structure, while at Tf the chain undergoes a transition
      to the native conformation. We show that foldability of sequences can be
      characterized entirely in terms of these two temperatures. It is shown that fast
      folding sequences have small values of sigma = (T theta - Tf)/T theta whereas
      slow folders have larger values of sigma (the range of sigma is 0 < sigma < 1).
      The calculated values of the folding times correlate extremely well with sigma.
      An increase in sigma from 0.1 to 0.7 can result in an increase of 5-6 orders of
      magnitudes in folding times. In contrast, we demonstrate that there is no useful
      correlation between folding times and the energy gap between the native
      conformation and the first excited state at any N for any value of B0. In
      particular, in the parameter space of the model, many sequences with varying
      energy gaps, all with roughly the same folding time, can be easily engineered.
      Folding sequences in this model, therefore, can be classified based solely on the
      value of sigma. Fast folders have small values of sigma (typically less than
      about 0.1), moderate folders have values of sigma in the approximate range
      between 0.1 and 0.6, while for slow folders sigma exceeds 0.6. The precise
      boundary between these categories depends crucially on N and on the model. The
      range of sigma for fast folders decreases with the length of the chain. At
      temperatures close to Tf fast folders reach the native conformation via a native
      conformation nucleation collapse mechanism without forming any detectable
      intermediates, whereas only a fraction of molecule phi (T) reaches the native
      conformation by this process for moderate folders. The remaining fraction reaches
      the native state via three-stage multipathway process. For slow folders phi (T)
      is close to zero at all temperatures. The simultaneous requirement of native
      state stability and kinetic accessibility can be achieved at high enough
      temperatures for those sequences with small values of sigma. The utility of these
      results for de novo design of proteins is briefly discussed.

PMID- 8990497
TI  - Dynamics of Fusarium solani cutinase investigated through structural comparison
      among different crystal forms of its variants.
AB  - In characterizing mutants and covalently inhibited complexes of Fusarium solani
      cutinase, which is a 197-residue lipolytic enzyme, 34 variant structures,
      crystallizing in 8 different crystal forms, have been determined, mostly at high
      resolution. Taking advantage of this considerable body of information, a
      structural comparative analysis was carried out to investigate the dynamics of
      cutinase. Surface loops were identified as the major flexible protein regions,
      particularly those forming the active-site groove, whereas the elements
      constituting the protein scaffold were found to retain the same conformation in
      all the cutinase variants studied. Flexibility turned out to be correlated with
      thermal motion. With a given crystal packing environment, a high flexibility
      turned out to be correlated with a low involvement in crystal packing contacts.
      The high degree of crystal polymorphism, which allowed different conformations
      with similar energy to be detected, made it possible to identify motions which
      would have remained unidentified if only a single crystal form had been
      available. Fairly good agreement was found to exist between the data obtained
      from the structural comparison and those from a molecular dynamics (MD)
      simulation carried out on the native enzyme. The crystallographic approach used
      in this study turned out to be a suitable tool for investigating cutinase
      dynamics. Because of the availability of a set of closely related proteins in
      different crystal environments, the intrinsic drawback of a crystallographic
      approach was bypassed. By combining several static pictures, the dynamics of the
      protein could be monitored much more realistically than what can be achieved on
      the basis of static pictures alone.

PMID- 8990498
TI  - Computational design of a substrate specificity mutant of a protein.
AB  - The wild-type trp repressor of E. coli bound 5-methoxytryptophan, a Trp analogue,
      less tightly than Trp. A mutant repressor (Val58-->Ala) that should bind 5
      methoxytryptophan preferentially to Trp was computationally designed by free
      energy calculations accompanied by free-energy decomposition. The designed mutant
      was demonstrated by experiments to bind 5-methoxytryptophan more tightly than
      Trp, consistent with the computational prediction. This success indicates the
      usefulness of free energy decomposition in protein design.

PMID- 8990499
TI  - Stability and folding of the SH3 domain of Bruton's tyrosine kinase.
AB  - Bruton's tyrosine kinase (BTK) plays an important role in B cell development.
      Deletion of C-terminal 14 amino acids of the SH3 domain of BTK results in X
      linked agammaglobulinemia (XLA), an inherited disease. We report here on the
      stability and folding of SH3 domain of BTK. Peptides corresponding to residues
      216-273 (58 residues) and 216-259 (44 residues) of BTK SH3 domain were
      synthesized by solid phase methods; the first peptide constitutes the entire SH3
      domain of BTK while the latter peptide lacks 14 amino acid residues of the C
      terminal. The 58 amino acid peptide forms mainly a beta-barrel type folding unit.
      Although small and lacking disulfide bonds, this peptide is extremely stable to
      thermal denaturation. Based on circular dichroism measurements, its melting
      temperature was found to be high, 82 degrees C at pH 6.0. However, the Gibbs free
      energy (delta GH2O) of the intrinsic stability and thermodynamic spontaneity of
      unfolding were found to be low, 2.6 kcal/mol by Gdn.HCl denaturation experiments,
      as compared to 12 kcal/mol obtained for larger single domain proteins, indicating
      poor stability of SH3 domain. Addition of 500 mM of Na2SO4 increased the free
      energy change delta GH2O to 4.0 kcal/mol, suggesting an ionic strength effect.
      The truncated peptide fails to fold correctly and adopts random coil conformation
      in contrast to 58 amino acid beta-barrel peptide, which exhibits high thermal
      stability but normal or low stability at ambient temperature. These results, to
      our knowledge the first to delineate the importance of C-terminal in structural
      integrity of SH3 domains, indicate also that improper folding and/or poor
      stability of mutant SH3 domain in BTK likely causes XLA.

PMID- 8990500
TI  - Molecular modeling of vimentin filament assembly.
AB  - Intermediate-filament forming proteins are known to form rod-shaped dimers that
      are calculated to be 45 nm in length. Molecular modeling indicates that the
      dimerization is promoted by interchain hydrophobic interactions between sections
      of alpha helix and beta helix. Further aggregation involves the formation of
      tetramers in which two dimers are anti-parallel and staggered to two
      characteristic degrees of overlap. Modeling indicated that the degrees of stagger
      are dictated by the association of sections of alpha helix in 4-chain bundles, in
      which hydrophobic side chains are sequestered from contact with water. The
      staggered arrangement of two dimers produces a tetramer having sections of 2
      chain rod in which hydrophobic side chains are exposed to water. Extension of the
      tetramer to form protofilaments may be driven by associations with the 2-chain
      regions that reduce aqueous exposure of the hydrophobic side chains. Exposure of
      hydrophobic groups may be reduced by the 2-chain regions folding back upon
      themselves so that the entire tetramer becomes a 4-chain conformation. This
      prediction is in line with electron microscope data showing that mixtures of the
      lower oligomers contain rods of uniform thickness ranging upwards from 45 nm in a
      series having incremental increases in length. Data from previous chemical
      crosslinking studies support this model and also the idea that the completed
      intermediate filaments each consist of seven 4-chain protofilaments.

PMID- 8990501
TI  - Crystallization of the bifunctional methylenetetrahydrofolate
      dehydrogenase/methenyltetrahydrofolate cyclohydrolase domain of the human
      trifunctional enzyme.
AB  - Methylenetetrahydrofolate([H4] folate) dehydrogenase (D) and methenyl[H4] folate
      cyclohydrolase (C) coexist as a bifunctional enzyme (DC) or as the amino-terminal
      domain of a trifunctional enzyme (DCS) where the third activity is 10
      formyl[H4]folate synthetase (S). Two crystal forms of the DC domain of the human
      cytosolic DCS enzyme have been grown from polyethyleneglycol solution. The
      monoclinic P2(1) crystals diffract to 2.8 A with a = 72.5 A, b = 68.5 A, c =
      125.2 A, and beta = 91.8 degrees but were found to be twinned. The orthorhombic
      P2(1)2(1)2(1) crystals diffract to 2.5 A with a = 67.7 A, b = 135.9 A, c = 61.6
      A, and contain two molecules per asymmetric unit.

PMID- 8990502
TI  - Crystallization of the NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase
      from Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae possesses three isozymes of 5,10
      methylenetetrahydrofolate dehydrogenase (MTD). The NAD-dependent enzyme is the
      first monofunctional form found in eukaryotes. Here we report its crystallization
      in a form suitable for high-resolution structure. The space group is P4(2)2(1)2
      with cell constants a = b = 75.9, c = 160.0 A, and there is one 36 kDa molecule
      in the asymmetric unit. Crystals diffract to 2.9 A resolution.

PMID- 8990503
TI  - The effect of topical steroid on the actions of vasoconstrictor and vasodilator
      peptides in human skin.
AB  - The effect of topical application of clobetasol propionate ointment (0.05% w/v)
      on the vascular changes induced by intradermal injections of histamine,
      calcitonin gene-related peptide, substance P, endothelin-1 and compound 48/80 was
      studied. Clobetasol propionate ointment was applied topically under occlusion to
      the forearm skin of healthy volunteers and vehicle base was applied to the
      contralateral forearm. The intradermal injections were made 4 h or, in a separate
      study, 72 h after topical steroid application. Responses were measured by
      planimetry and laser Doppler flowmetry. Four hours application of steroid did not
      significantly alter the responses to any of the vasoactive substances. After 72
      hours application, clobetasol propionate significantly increased the size of the
      endothelin-1-induced area of vasoconstriction (p < 0.02) and significantly
      reduced the size of the flares induced by endothelin-1 (p < 0.02), substance P (p
      < 0.009) and compound 48/80 (p < 0.05). We conclude that the most likely
      explanation of our data is an inhibition by the steroid of cutaneous mast cell
      function.

PMID- 8990505
TI  - Topical R-85355, a potent and selective 5-lipoxygenase inhibitor, fails to
      improve psoriasis.
AB  - Inhibitors of 5-lipoxygenase have been studied with respect to antipsoriatic
      efficacy. Of these compounds, R-68151 is of particular interest as it proved to
      inhibit 5-lipoxygenase without inhibiting 12-lipoxygenase, cyclooxygenase and
      thromboxane-A2 synthetase. R-68151 has been shown to have a mild-to-moderate
      therapeutic effect in psoriasis. In the present study a new 5-lipoxygenase, R
      85355, was investigated with respect to its efficacy in psoriasis. R-85355 is 3
      times more potent compared to R-68151 with respect to inhibition of in vitro A
      23187-stimulated leukotriene-B4 production by polymorphonuclear leukocytes. In a
      left-right double-blind comparative study, the compound was studied at saturation
      with respect to its antipsoriatic efficacy in 11 patients with chronic stable
      plaque psoriasis. In addition, various markers for epidermal proliferation,
      keratinization and inflammation were assessed. In no single patient was a left
      right difference observed in favour of R-85355 compared to placebo with respect
      to clinical severity scores or the cell-biological markers. The present study
      indicates that a selective and highly potent 5-lipoxygenase inhibitor was not
      effective in the topical treatment of chronic plaque psoriasis.

PMID- 8990506
TI  - Regional variation of nonimmunologic contact urticaria. Functional map of the
      human face.
AB  - BACKGROUND AND DESIGN: Benzoic acid (BA) was used to induce nonimmunologic
      contact irritation in 10 younger (23-47 years old) and 5 older (72-90 years old)
      healthy volunteers. BA 2.5% in petrolatum was applied to 8 locations on the face,
      neck and volar forearm. Changes in the skin blood flow were monitored using a
      laser Doppler flowmeter. Also measured at each location were baseline
      measurements of skin blood flow, transepidermal water loss, stratum corneum
      hydration, skin surface temperature and skin surface pH. RESULTS: The neck area
      exhibited the greatest reaction in both age groups while the forearm exhibited
      the least. At each site tested, the younger group consistently demonstrated
      greater reactivity to BA. A significant correlation was noted between stratum
      corneum hydration and irritation. CONCLUSIONS: This information provides a basis
      to further study the frequent poorly understood intolerance of the face to
      topical formulation.

PMID- 8990504
TI  - Evaluation of topical antipsoriatic treatment by chromametry, visiometry and 20
      MHz ultrasound in the psoriasis plaque test.
AB  - The antipsoriatic effects of two topical antipsoriatic agents, betamethasone
      valerate (Betnovate) and calcipotriol (Daivonex), and a pure nanocolloid gel were
      assessed in 10 patients with chronic plaque-type psoriasis in a modified
      psoriasis plaque test. Three noninvasive bioengineering methods were applied to
      measure antipsoriatic effects: chromametry for objective evaluation of erythema;
      visiometry, a method for profilometry, and 20-MHz skin ultrasound for the
      measurement of skin thickness as a parameter of inflammatory infiltration and
      psoriatic hyperproliferation of the epidermis. Regarding inflammation parameters
      such as skin thickness (infiltration) and erythema (dilatation of vessels and
      hyperperfusion), the steroid preparation Betnovate proved to be significantly
      most effective in our study. Daivonex showed significant decreases in the skin
      roughness parameters, underlining its antiproliferative effect. The nanocolloid
      carrier was significantly effective in thickness reduction, this effect being
      most probably due to occlusion. 20-MHz ultrasound, chromametry and visiometry
      proved to provide multiparameter assessment of treated and untreated psoriatic
      skin and can be recommended as objective and reproducible measurements for
      further studies.

PMID- 8990507
TI  - Plasma retinoids after topical use of retinaldehyde on human skin.
AB  - BACKGROUND: Retinaldehyde (RAL), a natural metabolite of beta-carotene and
      retinol (ROL), is tolerated by human skin after topical application. PURPOSE: To
      see if topical application of a large quantity of RAL on human skin is associated
      with a detectable alteration of constitutive levels of plasma retinoids resulting
      from metabolism of RAL in the skin. METHODS: Plasma retinoids [ROL, all-trans
      retinoic acid (all-trans-RA), RAL, retinyl palmitate/oleate, 13-cis-RA and 4-oxo
      13-cis-RA] were analyzed by high-pressure liquid chromatography. Determinations
      were done in 10 healthy male volunteers kept on a vitamin-A-poor diet before,
      during and after daily topical application of 7 mg of RAL to 40% of the body
      surface for 14 days. RESULTS: The introduction of a restricted vitamin A diet
      before RAL application resulted in a decrease in the plasma levels of ROL, all
      trans-RA and retinyl palmitate/oleate. Topical application of RAL did not induce
      an alteration of the plasma levels of retinoid metabolites. No RAL was detectable
      in any of the plasma samples. CONCLUSION: The skin metabolism of topically
      applied RAL does not result in detectable alterations of constitutive levels of
      plasma retinoids in humans.

PMID- 8990508
TI  - No effect of albumin on the dermal absorption rate of hydrocortisone 21-butyrate,
      permethrin or diflunisal in the isolated, single-pass perfused rabbit ear.
AB  - Rabbit ears were single-pass perfused with a buffer solution containing either 6%
      hetastarch or 5% bovine serum albumin. Hydrocortisone 21-butyrate (5 mM),
      diflunisal (17 mM) or permethrin (33 mM) was added to isopropyl myristate with 5%
      polyethylene, and applied to about 40% of the epithelial surface area of the ear.
      Hydrocortisone 21-butyrate or permethrin were not found in the effluent with
      hetastarch or albumin. Following cutaneous ester hydrolysis, the appearance rate
      of hydrocortisone was about 4 pmol/min per cm2 in the hetastarch- or the albumin
      containing buffer solution. No hydrolysis of permethrin was detected; the
      appearance rate of 3-phenoxybenzyl alcohol with 3-phenoxybenzoic acid
      corresponded to the absorption rate of the substrate impurities. During ex vivo
      perfusion of intact skin, serum albumin in the perfusion fluid may not enhance
      the appearance rate of xenobiotics in the effluent following dermal application
      when the distribution coefficient n-octanol/water is > 2,000 or when the
      xenobiotic is ionized at physiological pH. In general, for all substances
      investigated with our perfusion model thus far, the appearance rates decreased
      with rising distribution coefficient (n-octanol/buffer pH 7.4). High
      lipophilicity hinders the release from isopropyl myristate and the penetration
      through the skin.

PMID- 8990510
TI  - Lyme borreliosis.

PMID- 8990509
TI  - A model to assess the effectiveness of topical antipruritics.
AB  - A model has been developed to determine the effectiveness of topical
      antipruritics. It utilizes controlled, experimentally induced itch and has
      demonstrated the effectiveness of the direct action on cutaneous receptor sites
      of a topical anesthetic, benzocaine, in a topical antipruritic formulation, and
      has been used to differentiate between two effective topical antipruritics. Three
      studies are presented: The first study examined the reliability of the
      experimentally induced itch. Several indices of reliability were computed from
      the data of this first study. Cronbach's alpha was 0.92. Winer's theta also was
      0.92. Simple test-retest reliability, computed at intervals of 29 min, 1 day, and
      6-7 days, resulted in Pearson correlations of 0.84, 0.73, and 0.60, respectively.
      In the second study, the model differentiated statistically between the itch
      relief resulting from the topical application of a formulation with 6% benzocaine
      and the same formulation without benzocaine. The third study examined 2 known
      topical antipruritics: one containing 6% benzocaine and the other 1%
      hydrocortisone. Both topical antipruritics were found to relieve itch; however,
      the benzocaine antipruritic produced statistically significantly greater itch
      relief in more subjects than the hydrocortisone antipruritic at both 1 and 30 min
      after application. These results demonstrate that OTC antipruritics can be
      differentiated for effectiveness.

PMID- 8990511
TI  - European Union Concerted Action on Risk Assessment in Lyme Borreliosis: clinical
      case definitions for Lyme borreliosis.
AB  - The EU Concerted Action on Risk Assessment in Lyme Borreliosis (EUCALB) has
      consulted other clinicians and scientists in Europe to produce case definitions
      of the principal manifestations of European Lyme borreliosis. These case
      definitions will not only be helpful in supporting its own research interests,
      but are also intended to assist other clinicians in appropriate management and to
      support further studies aimed at determining the full clinical spectrum of the
      disease. The case definitions were achieved after a series of meetings organised
      by EUCALB with other expert clinicians and scientists from twelve European
      countries. The definitions and the diagnostic criteria presented thus represent
      the consensus reached at these meetings. The proposed case definitions consider
      skin, nervous system, cardiac and musculoskeletal presentations and the role of
      laboratory investigation in supporting diagnosis.

PMID- 8990512
TI  - Genetic diversity of Borrelia of Lyme borreliosis.

PMID- 8990513
TI  - Cytogenetic findings in colorectal cancer mirror multistep evolution of
      colorectal cancer.
AB  - Successful cytogenetic analysis was performed on tumor material from 26 patients
      with resectable colorectal cancer. 9 women and 17 men, aged 43 to 92 years,
      median 67 years. Clonal anomalies were found in twenty patients; five tumors
      showed mainly slight numerical changes such as trisomy 7 and loss of Y (2 cases).
      The remaining 15 tumors had highly complex karyotypes. The mainline was near
      diploid in six cases (5/6 tumors of the proximal colon), near triploid in four
      and near tetraploid in five tumors. Loss of chromosomes was most frequently
      observed with chromosomes 2, 5, 18, 20, and Y, the most frequently gained
      chromosomes were 7, 8, 13, 15, and X. Structural aberrations affected all
      chromosomes, except Y. The most frequently rearranged bands were 5q21, 7p15,
      9p21, 13q11, 16p12, 17p13, 18q21, 21q11. Anomalies of chromosomes 5, 17, and 18
      occurred concomitantly in 9/20 patients. All patients with deletions of 17p (n =
      6) had near tetraploid karyotypes with high cell to cell variability and a median
      of nine structural aberrations (p < 0.007); four of them presented with
      parenchymal metastases at the time of surgery. Tumors of the proximal part of
      colon were with one exception diploid or near diploid, but no specific pattern of
      aberrations was detectable. However, it appears noteworthy that of the six
      patients with tumors of the ascending colon, three tumors had deletions at 16p12
      and the affected patients had a short duration of survival. The tumor karyotypes
      of patients with parenchymal metastases revealed a trend to greater complexity of
      numerical and structural aberrations. Changes involving 8p22 or loss of
      chromosomes 8 were found in tumors of all parts of the colon and potentially
      associated with an unfavorable prognosis (4/7 decreased patients showed such
      changes).

PMID- 8990514
TI  - Morbus Skerljevo--an unknown disease among Slovenians in the first half of the
      19th century.
AB  - During the first decades of the 19th century a disease appeared in the regions of
      Inner Carniola and Carst which was, due to its unusual course, at first
      considered a new entity. It spread among the population in an asexual,
      extragenital and endemic way and was conditioned by poor economic and hygienic
      circumstances. Since the clinical picture of the disease resembled sporadic
      syphilis, some doctors thought that it was a combination of syphilis and some
      other contagious disease, while others likened it to sporadic syphilis. The
      government in Vienna responded to the epidemic by the introduction of extensive
      social and health measures. Compulsory medical examination of all the inhabitants
      in the affected areas was decreed, treatment of patients was initiated and
      preventive measures recommended. The action was organised by Baron Dr. Stifft. In
      the summer of 1818 a new specialised hospital for Skerljevo's patients was opened
      in Postojna (Adelsberg). When the epidemic declined a decade later the hospital
      was closed down. Extensive preventive and curative actions, and the efforts of
      local authorities and clergy to improve living conditions of the Slovenian
      peasant population and make them more aware of the seriousness and causes of the
      disease contributed to the decline of the epidemic. The example set by
      organisation of the official measures taken in the case of Skerljevo disease can
      serve as a basis for a comparative medico-historical study regarding new epidemic
      diseases (AIDS, and diseases caused by slow viruses).

PMID- 8990515
TI  - A biomechanical investigation into the absence of leaping in the locomotor
      repertoire of the slender loris (Loris tardigradus).
AB  - Unlike all other primates, members of the subfamily Lorisinae are never seen to
      leap. To investigate the anatomical specializations that are behind the absence
      of leaping in their locomotor repertoire, a predictive mechanical model of
      leaping was developed using the lesser bushbaby, Galago moholi, as a size-matched
      leaping prosimian comparison. This enabled the required limb movements for a
      leaping slender loris to be calculated, and hence the torque and power
      requirements at each of the hindlimb joints. From this information, the maximum
      feasible leap was calculated for the slender loris morphotype; and it was found
      that this alone would prevent the animal from leaping a greater distance than it
      could walk over, so that the reduction in fitness due to an apparent loss of
      leaping from the behavioural repertoire can be considered to be very small.

PMID- 8990516
TI  - Geometric morphometrics in primatology: craniofacial variation in Homo sapiens
      and Pan troglodytes.
AB  - Traditionally, morphometric studies have relied on statistical analysis of
      distances, angles or ratios to investigate morphometric variation among taxa.
      Recently, geometric techniques have been developed for the direct analysis of
      landmark data. In this paper, we offer a summary (with examples) of three of
      these newer techniques, namely shape coordinate, thin-plate spline and relative
      warp analyses. Shape coordinate analysis detected significant craniofacial
      variation between 4 modern human populations, with African and Australian
      Aboriginal specimens being relatively prognathous compared with their Eurasian
      counterparts. In addition, the Australian specimens exhibited greater basicranial
      flexion than all other samples. The observed relationships between size and
      craniofacial shape were weak. The decomposition of shape variation into affine
      and non-affine components is illustrated via a thin-plate spline analysis of Homo
      and Pan cranial landmarks. We note differences between Homo and Pan in the degree
      of prognathism and basicranial flexion and the position and orientation of the
      foramen magnum. We compare these results with previous studies of these features
      in higher primates and discuss the utility of geometric morphometrics as a tool
      in primatology and physical anthropology. We conclude that many studies of
      morphological variation, both within and between taxa, would benefit from the
      graphical nature of these techniques.

PMID- 8990517
TI  - Occurrence of an infanticide within a captive polygynous group of common
      marmosets, Callithrix jacchus.

PMID- 8990518
TI  - Determination of the gas-phase basicities of proline and its di- and tripeptides
      with glycine: the enhanced basicity of prolylproline.
AB  - The gas-phase basicity (GB) of proline, which is the only imino acid and is
      reported to play a significant role in protein folding, was determined by
      deprotonation reactions in a Fourier transform ion cyclotron resonance (FT-ICR)
      mass spectrometer. Protonated peptide ions were generated by fast atom
      bombardment in an external ion source. The GB of proline was found to be 213.3
      kcal/mol. Among the dipeptides studied, the GB of glycylproline (GlyPro) was
      determined to be 214.8 kcal/mol, while prolyglycine (ProGly) was 4.2 kcal/mol
      more basic (GB = 219.0 kcal/mol). The basicity of the tripeptide
      prolylglycylglycine (ProGlyGly, GB = 219.0 kcal/mol) is 2 kcal/mol higher than
      the basicities of glycylglycylproline (GlyGlyPro) and glycylprolylglycine
      (GlyProGly), both of which have GB = 217.0 kcal/mol. The enhanced basicity of
      ProGlyGly is consistent with the protonation site being the terminal amino
      nitrogen with enhanced stabilization of the charge by the nearby bulkier residue.
      Interestingly, prolyproline (ProPro), which has a GB of 223.3 kcal/mol, is more
      basic than the other di- and tripeptides studied. Consequently, semi-empirical
      AM1 calculations were employed to probe the structural characteristics and
      intramolecular hydrogen bonding interactions for ProPro, GlyPro, ProGly and
      glycylglycine (GlyGly). ProPro was found to have a unique structure with two
      potential hydrogen bonds between amino hydrogens and both carbonyl oxygens.

PMID- 8990519
TI  - A confirmatory HPLC-MS/MS method for ten synthetic corticosteroids in bovine
      urines.
AB  - In the present study, an HPLC-MS/MS method to confirm, in bovine urine, the most
      common synthetic corticosteroids illegally used as growth promoters in livestock
      breeding will be presented. An API III-Plus (PE-Sciex) triple quadrupole mass
      spectrometer, interfaced by means of an atmospheric pressure chemical ionization
      source to the HPLC system, was used. Urine samples were treated with a sulfatase
      glucuronidase mixture to cleave the drug-conjugates and then extracted on C18
      disposable columns. LC separations were performed on a reversed-phase C18 column
      with ammonium acetate 0.1 M/acetonitrile (60/40, v/v) as mobile phase. Detection
      was performed in multiple reaction monitoring mode, negative ions, selecting
      fragmentations characteristic of 10 corticosteroids used more frequently. Good
      results, in terms of sensitivity and specificity have been obtained for nine
      corticosteroids that can be analyzed in the same HPLC run; the limits of
      sensitivity achieved were 0.05-1.0 ng/ml in urine. Only a more polar
      corticosteroid, required a different HPLC separation. Practical applications of
      this technique to real samples proved that it is an effective method to confirm
      the illegal use of corticosteroids as growth promoter in animal. In comparison
      with the chemical GC-MS methods the simpler sample preparation and the faster
      time of analysis permit a considerable increase of sample testing per day without
      compromising on analytical sensitivity and specificity.

PMID- 8990520
TI  - Identification of talinolol metabolites in urine of man, dog, rat and mouse after
      oral administration by high-performance liquid chromatography-thermospray tandem
      mass spectrometry.
AB  - A new specific HPLC-TSP-MS/MS assay for identification of beta-blocking drug
      talinolol and its metabolites in urinary samples of man, dog, rat and mouse after
      single oral administration has been developed. Centrifuged urines were directly
      injected into the HPLC-TSP-MS system. Based on thermospray MS/MS studies of 10
      reference compounds, several selective CID-MS/MS reactions were found, which were
      typical of substructure elements of potential phase I metabolites. In this way
      the differentiation of various stereochemical positions of the hydroxyl group in
      the cyclohexyl ring moiety of metabolites was possible. Renal metabolic profiles
      for all investigated species were generated by HPLC-multiple reaction monitoring
      (MRM). The detected metabolites were characterized by TSP full scan and MS/MS
      analysis in relation to synthesized reference compounds. The major metabolic
      pathway in all species results in the hydroxylation of the cyclohexylring moiety
      of talinolol. In dog urine, a phase II metabolite, the O-glucuronide of talinolol
      (I) was found. In order to identify this structure, the use of electrospray
      ionization was also necessary.

PMID- 8990521
TI  - 15N conservation in the metabolic conversion of isoleucine to alloisoleucine in
      the rat.
AB  - 15N,13C6-L-Isoleucine was given by stomach tube to a pair of rats and the urine
      excreted over the following 6 h period was collected. The urinary amino acid
      fraction showed that the majority of the L-alloisoleucine produced from the
      labeled isoleucine was formed with the 15N label intact. This fails to support
      the commonly held supposition that L-isoleucine and L-alloisoleucine
      interconversion occurs through the reversible enolization of the 2-keto-3
      methylvaleric acids formed by their transamination. In contrast to 15N label
      conservation in L-alloisoleucine, the majority of the 15N in the administered L
      isoleucine underwent exchange with 14N.

PMID- 8990522
TI  - Quantification of acetylcholine in cell culture systems by semi-micro high
      performance liquid chromatography and electrospray ionization mass spectrometry.
AB  - Electrospray ionization (ESI) was used to adapt the thermospray ionization liquid
      chromatographic/mass spectrometric (LC/MS) method of Liberato et al. to the
      determination of acetylcholine and choline released from cells in culture. A
      clonal cell line derived from a rat pheochromocytoma (PC12) was used and cultures
      depolarized in the presence of cholinesterase inhibitor to maximize the recovery
      of acetylcholine from the culture medium and protect against its hydrolysis.
      Concentration of acetylcholine and choline released into the incubation medium
      was accomplished with Sep-Pak C16 cartridges. The preformed analyte cations were
      resolved by reversed-phase high-performance liquid chromatography and analyzed
      without derivatization by electrospray ionization mass spectrometry with the use
      of acetyl[2H9]choline as internal standard. LC/MS allows for the direct
      determination of acetylcholine and choline, which is not possible with other
      methods.

PMID- 8990524
TI  - Negative ion electrospray mass spectrometry of polyphenols, catecholamines and
      their oxidation products.
AB  - Polyphenols, catecholamines and their oxidation products have a variety of
      physiological effects and are key components of insect cuticle and other
      biological structures. Three dihydroxybenzene isomers were easily differentiated
      using negative ion electrospray mass spectrometry (ESMS) or tandem mass
      spectrometry (MS/MS). Ions at m/z 107-109 were diagnostic for more complex
      polyphenols and catecholamines with a dihydroxybenzene moiety. The product ion
      spectra of other compounds including 3,4-dihydroxyphenylacetic acid, 3,4
      dihydroxyphenylalanine (DOPA) and N-acetyldopamine (NADA) had product ions at m/z
      121-123 corresponding to methylene homologues of dioxygenated benzene. Oxidation
      of DOPA using tyrosinase, Ag2O or NaIO4 could be followed using ESMS and several
      proposed intermediates proceeding from DOPA through a quinone methide
      intermediate, 5,6-dihydroxyindole and dihydroxyindole quinone were confirmed
      using negative ion ESMS/MS. Spectra of the NaIO4 oxidation products of 1,2,3
      trihydroxybenzene (pyrogallol) were consistent with tetrahydroxybenzene, two non
      cyclic tetraoxygenated derivatives and a bicyclic polymerization product,
      purpurogallin. ESMS can be used to analyse complex polyphenolic conjugates
      commonly encountered in biological specimens.

PMID- 8990523
TI  - Classification of species in the genus Penicillium by Curie point pyrolysis/mass
      spectrometry followed by multivariate analysis and artificial neural networks.
AB  - Curie point pyrolysis/mass spectrometry of Penicillium species was performed with
      530 degrees C Curie point foils. The mass spectra were submitted to principal
      component analysis, canonical variates analysis and hierarchical cluster
      analysis, producing a final dendrogram by the use of average linkage clustering.
      By this approach a successful classification of the species Penicillium italicum,
      P. expansum and P. digitatum originating from fruits was obtained. Isolates of
      the same species grouped together in the dendrogram, while the different species
      were distinguished. Also when grown on two different agar media, replicates of
      the same species grouped together. Likewise, a satisfactory classification was
      achieved by multivariate analysis of the data for various isolates of the cheese
      associated fungi Aspergillus versicolor, P. discolor, P. roqueforti, P. solitum,
      P. verrucosum, P. commune and P. palitans. However, some difficulties appeared in
      distinguishing the closely related species P. commune and P. palitans. Such
      difficulties became greater on including more isolates and limiting the analysis
      to five of the species. The use of back-propagation artificial neural networks,
      in contrast, resulted in a correct classification in all cases. Thus, it is
      concluded that Curie point pyrolysis/mass spectrometry is useful in
      chemotaxonomic studies of the closely related species in the genus Penicillium.

PMID- 8990525
TI  - [Skin manifestation of allergic diseases and collagen disease].

PMID- 8990526
TI  - [Clinical features of allergic granulomatosis and angiitis (Churg-Strauss
      syndrome). Association with asthma symptoms].
AB  - We reported clinical and laboratory findings of 5 patients with Churg-Strauss
      syndrome (CSS), especially association with asthma symptoms. Subjects included 3
      males and 2 females with a mean age of 53.8 year-old. In all 5 patients symptoms
      of neuropathy; mononeuritis multiplex and in some patients, other vasculitic
      symptoms; fever, diarrhea, abdominal pain and skin eruptions, were noted. These
      clinical features and laboratory findings; marked peripheral eosinophilia and
      elevation of serum ECP were normalized after steroid therapy. We investigated the
      relation between the occurrence of CSS and the symptoms of asthma. The mean
      duration of asthma in this series was 17.2 years, and 4 cases were atopic and one
      was non-atopic asthma. In previous publications, asthmatic symptoms were severe
      at the onset of the disease and progressed thereafter. In our 5 cases, however,
      the severities of bronchial asthma were mild of two cases, moderate of two and
      severe of only one, moreover severe asthmatic attacks were shown in only 2 cases
      when the manifestation of systemic vasculitis occurred. In conclusion, although
      CSS has been thought that one of complications of bronchial asthma, the
      occurrence of CSS are not necessarily correlated with symptoms of bronchial
      asthma.

PMID- 8990527
TI  - [Serum eosinophil cationic protein in infants during first wheezing episode].
AB  - We measured serum ECP levels in infants during first wheezing episode. Serum ECP
      in these infants are significantly higher than in control infants, although much
      higher in children with asthma. Serum ECP in these infants with high serum IgE
      and/or positive RAST score are higher than in infants with normal serum IgE and
      negative RAST score. In children with bronchial asthma serum ECP is correlated
      with peripheral eosinophil counts, but in infants during first wheezing episode
      serum ECP is often elevated not associated with increased peripheral eosinophil
      counts. These suggest that activated eosinophils could be responsible for
      bronchoconstriction in wheezing patients with atopic diathesis even in very early
      phase and that these eosinophilic inflammations could contribute to formation of
      increased airway reactivity and bronchial asthma.

PMID- 8990528
TI  - [Inhibitory effect of ONO-1078, a novel leukotriene receptor antagonist, on human
      peripheral blood eosinophils].
AB  - To determine whether ONO-1078, leukotriene receptor antagonist, inhibits the
      activation of eosinophils, we investigated the effect of ONO-1078 on the release
      of leukotriene (LTC4) and eosinophil cationic protein (ECP) from human peripheral
      blood eosinophils of allergic patients and normal subjects. After preincubation
      with ONO-1078, eosinophils were incubated with calcium ionophore (A23187). ONO
      1078 10(-5) and 10(-6) M inhibited LTC4 release of allergic patients eosinophils
      and 10(-5)-10(-9) M inhibited LTC4 release of normal subjects eosinophils. ONO
      1078, 10(-5) M, also inhibited ECP release of eosinophils obtained from both
      asthma patients and normal subjects. We think that ONO-1078 may have another
      pharmacological effect to prevent the activation of human peripheral blood
      eosinophils by inhibiting LTC4 and ECP release. These results suggest that ONO
      1078 might be useful in controlling bronchial asthma.

PMID- 8990529
TI  - [Evaluation of efficacy for Japanese cedar pollen-specific immunotherapy by
      lymphocyte proliferation test].
AB  - Peripheral mononuclear cells from 47 patients suffering from Japanese cedar
      pollinosis were stimulated with crude pollen extract of Cryptomeria Japonica (CJ)
      to evaluate the effect of CJ-specific immunotherapy. The stimulation index (SI)
      with crude pollen extract of CJ in the patients with excellent and good clinical
      outcome was significantly lower than those with poor outcome. The SI increased
      with the increasing symptoms in a dose dependent manner. In the patients under
      immunotherapy for long period, the good clinical outcome and low SI were gained.
      These results suggest that peripheral lymphocyte proliferation test should be a
      good objective indicator for allergen-specific immunotherapy.

PMID- 8990530
TI  - [A case of allergic bronchopulmonary aspergillosis following active pulmonary
      tuberculosis].

PMID- 8990531
TI  - [A case of toxic shock syndrome associated with atopic dermatitis].

PMID- 8990532
TI  - Differential maternal treatment of infant twins: effects of infant behaviors.
AB  - This project utilized twins to study differential mother-sibling interactions.
      The use of twins circumvented the traditional confounds of studying siblings of
      different ages or at two points in time. When the twins were 7 and 9 months of
      age, mothers spent 2.5 min alone with each infant in an attempt to elicit child
      vocalizations. The mother and infant behaviors were coded both microanalytically
      and globally. The infant attention behaviors were influenced primarily by unique
      environment, whereas the temperament behaviors were influenced by both unique
      environmental and genetic effects. Mothers tended to treat both children
      similarly, regardless of zygosity, suggesting that maternal characteristics drove
      the mother-infant interactions. Thus, even though identical twins were more
      similar on some measures than fraternal twins, mothers tended to treat both types
      of twins comparably regardless of infant characteristics or behaviors.

PMID- 8990533
TI  - Life events and personality in late adolescence: genetic and environmental
      relations.
AB  - The relationship between life events and personality was investigated in the
      Minnesota Twin/Family Study, using 216 monozygotic and 114 dizygotic 17-year-old
      male twin pairs. Participants completed a life events interview designed for
      adolescents and the Multidimensional Personality Questionnaire. Life events were
      categorized into three types: life events to which all members of a family would
      be subject and those affecting an individual, which can be broadly construed as
      either nonindependent or independent. Univariate genetic model fitting indicated
      the presence of significant genetic effects (h2 = 49%) for nonindependent
      nonfamily life events but not for the other two types of life events. Bivariate
      genetic model fitting further confirmed that the significant phenotypic
      correlation between nonindependent life events and personality is in part
      genetically mediated. Specifically, the findings suggest that genetically
      influenced individual differences in constraint play a substantial role in life
      events whose occurrence is not independent of the individual's behavior.

PMID- 8990534
TI  - Genetic markers associated with high versus low performance on episodic memory
      tasks.
AB  - Associations were studied between six serum protein polymorphisms (C3, BF, HP,
      ORM, TF, and GC) and high versus low scoring on episodic memory tasks in an
      attempt to identify QTL (quantitative trait loci) contributing to the
      heritability of this quantitative trait. Since a highly significant sex
      difference (p = .00002) was found with respect to the distribution of high and
      low scoring, with men showing a poorer performance, associations were studied
      separately for males and females. In females significant differences (p < .05)
      between the high and the low groups were found in four of six marker systems (C3,
      HP, TF, and CG), whereas in males a significant difference was found only in the
      HP system. Significant differences from population frequencies were also found
      more frequently in females than in males. The strongest marker associations were
      found with complement C3 and the acute-phase reactant HP, which suggests that
      immune response factors may be of importance in preserving episodic memory
      function. The overall results appear to indicate that episodic memory is a
      multifactorial and heritable quantitative trait where sex is an important
      determinant.

PMID- 8990536
TI  - The effects of extended training and acute administration of an anxiolytic on
      avoidance learning and intertrial responding in the Syracuse strains of rats.
AB  - Male and female animals of the SHA/Bru and SLA/Bru strains of rats were given
      extended two-way avoidance training in the shuttle box at the rate of 30 trials
      per day for 11 days. SLA/Bru animals increased their avoidance responses (AVRs)
      from approximately 10 to roughly 25%, whereas animals of the SHA/Bru strain
      remained unchanged at approximately 100% AVRs. SHA/Bru animals made a number of
      intertrial responses (ITRs) early in the experiment; these declined after about 3
      days to the low level made by SLA/Bru animals. Chlordiazepoxide (CDP) had no
      effect on AVRs in animals of either strain, and had no effect on ITRs made by
      animals of the SHA/Bru strain, but increased ITRs, in a dose-dependent way, in
      animals of the SLA/Bru strain. These results are interpreted in terms of the well
      established genetic difference in emotional reactivity between animals of the two
      strains and in terms of genetically determined differences in sensitivity to
      anxiolytic drugs such as CDP.

PMID- 8990535
TI  - Intake of ethanol, sodium chloride, sucrose, citric acid, and quinine
      hydrochloride solutions by mice: a genetic analysis.
AB  - Mice of the 129/J (129) and C57BL/6ByJ (B6) strains and their reciprocal F1 and
      F2 hybrids were offered solutions of ethanol, sucrose, citric acid, quinine
      hydrochloride, and NaCl in two-bottle choice tests. Consistent with earlier work,
      the B6 mice drank more ethanol, sucrose, citric acid, and quinine hydrochloride
      solution and less NaCl solution than did 129 mice. Analyses of each generation's
      means and distributions showed that intakes of ethanol, quinine, sucrose, and
      NaCl were influenced by a few genes. The mode of inheritance was additive in the
      case of ethanol and quinine, for sucrose the genotype of the 129 strain was
      recessive, and for NaCl it was dominant. Citric acid intake appeared to be
      influenced by many genes with small effects, with the 129 genotype dominant.
      Correlations of sucrose consumption with ethanol and citric acid consumption were
      found among mice of the F2 generation, and the genetically determined component
      of these correlations was stronger than the component related to environmental
      factors. The genetically determined correlation between sucrose and ethanol
      intakes is consistent with the hypothesis that the higher ethanol intake by B6
      mice depends, in part, on higher hedonic attractiveness of its sweet taste
      component.

PMID- 8990537
TI  - Discussion of "methodological controversies in the treatment of panic disorder".

PMID- 8990539
TI  - Modelling cognition in emotional disorder: the S-REF model.
AB  - Cognitive therapy techniques are applied to an ever-increasing range of
      psychological disorders. However, both basic methods and general theory of
      therapy have evolved more slowly. Although cognitive therapy is based on
      experimentally testable concepts derived from cognitive psychology, an
      integration of these areas capable of explaining cognitive-attentional phenomena
      and offering treatment Implications remains to be achieved. In this paper, we
      outline the Self-Regulatory Executive Function (S-REF) model of emotional
      disorder, which integrates information processing research with Beck's schema
      theory. The model advances understanding of the roles of stimulus-driven and
      voluntary control of cognition, procedural knowledge (beliefs), and of the
      interactions between different levels of information-processing. It also accounts
      for cognitive bias effects demonstrated in the experimental psychopathology
      literature. The model presents implications concerning not only what should be
      done in cognitive therapy, but how cognitive change may be most effectively
      accomplished.

PMID- 8990538
TI  - Implicit memory bias in clinical and non-clinical depression.
AB  - Implicit memory for depression-relevant information was examined in non-clinical
      subjects with high versus low levels of dysphoria (Experiment 1), and in subjects
      who met DSM-III-R diagnostic criteria for depression versus normal controls
      (Experiment 2). The implicit memory test was a primed lexical decision task, with
      depression-relevant and neutral words, and suprathreshold and subthreshold
      primes. In Experiment 1, dysphoric subjects showed greater subthreshold priming
      of depression words than non-dysphoric subjects. In Experiment 2, clinically
      depressed individuals showed greater subthreshold and suprathreshold priming of
      depression words than normal non-depressed controls. The results confirmed those
      from previous studies using the primed lexical decision task to investigate
      implicit memory for negative information in depression (Bradley, Mogg & Williams,
      1994, Behaviour Research and Therapy, 32, 65-78; Bradley, Mogg & Williams, 1995,
      Behaviour Research and Therapy, 33, 755-770). Implications for recent cognitive
      models of depression are discussed.

PMID- 8990540
TI  - How to remain neutral: an experimental analysis of neutralization.
AB  - Many patients with obsessive-compulsive problems engage in neutralizing activity
      to reduce or "cancel out" the effects of the obsession. In many cases,
      neutralization is covert and therefore difficult to assess or manipulate
      experimentally. We hypothesize that neutralization resembles overt compulsions.
      In particular, it was predicted that: (i) neutralization reduces the anxiety
      evoked by unacceptable thoughts, and (ii) if neutralization is delayed, anxiety
      and the urge to neutralize will decay naturally. To test the hypothesis, 63 Ss
      prone to a cognitive bias known to be associated with obsessional complaints
      (thought-action fusion) were asked to write a sentence that would evoke anxiety.
      Measures of anxiety (and other variables of interest such as guilt,
      responsibility and the likelihood of harm) were taken. Subjects were then
      instructed to either immediately neutralize (n = 29) or delay for 20 min (n =
      34), after which time anxiety and urge to neutralize were re-assessed. The Ss who
      had neutralized were then instructed to delay, and the Ss who had delayed were
      now instructed to neutralize, after which time the final assessments were taken.
      The results confirmed the predictions and supported the hypothesis that
      neutralization resembles overt compulsions. Of note, there were no differences
      between anxiety reduction after a 20-min delay, and after immediate
      neutralization. The problems involved in designing and conducting experiments on
      covert phenomena are discussed, and the clinical implications of the study are
      considered.

PMID- 8990541
TI  - Vulnerability representation: the role of perceived dangerousness,
      uncontrollability, unpredictability and disgustingness in spider fear.
AB  - It was proposed that cognitive vulnerability representations relating to the
      perceived uncontrollability, unpredictability, dangerousness and disgustingness
      of spiders are important factors in the fear of spiders. One-hundred and ninety
      two first-year psychology students completed a questionnaire measuring the four
      vulnerability variables, spider fear and learning history. It was found that fear
      of spiders was highly correlated with each of the four vulnerability variables.
      In addition, greater fear of spiders was found for females in comparison with
      males and this was associated with differential perceptions of spiders as
      uncontrollable, unpredictable, dangerous and disgusting. Finally, the
      vulnerability variables accounted for significantly more variance in fear scores
      than the experience of a number of classical conditioning, vicarious and
      informational learning events. It is argued that there is value in considering a
      person's perception of the uncontrollability, unpredictability, dangerousness and
      disgustingness of spiders in order to better understand individual differences in
      spider fear.

PMID- 8990542
TI  - The disruptive nature of pain: an experimental investigation.
AB  - Pain interrupts, distracts and takes effort to ignore. Focusing our research
      attention upon this central aspect of pain experience, an experimental paradigm
      is introduced to study the disruptive nature of pain. Healthy volunteers were
      exposed several times to an electrical pain stimulus and a control stimulus. Tone
      probes were presented immediately (100 ms) and later on (1500 ms) after
      pain/control onset, and after pain/control offset (1000 ms). Results clearly
      showed disruption during pain. This disruptive effect was most marked immediately
      after onset. No differential results between pain and control conditions were
      observed later on during the pain experience. These results are interpreted
      within current cognitive and psychophysiological theories of attention. Emphasis
      is placed upon the importance of the experimental investigation of the role of
      attention in pain processing.

PMID- 8990543
TI  - Do pain expectancies cause pain in chronic low back patients? A clinical
      investigation.
AB  - The present study investigated whether pain expectancies cause pain in chronic
      low back patients. Back patients (N = 29) were requested to perform four exercise
      bouts (two with each leg), each consisting of flexing and extending the knee
      three times at maximal force (Cybex 350 System). During each exercise bout the
      baseline pain, the expected pain and experienced pain were recorded. Patients
      also reported their experienced fear of further injury to the back. Furthermore,
      the peak force of both knee flexors and extensors was assessed. Although patients
      did expect a back pain increase during the first exercise bout with each leg, no
      evidence was found for the thesis that pain expectancies generate increases in
      subjective pain experiences. Instead, the reported pain expectancy was readily
      corrected during the next exercise bout, whereas the experienced pain remained
      unchanged. Furthermore, a high pain expectancy co-occurred with (1) a marginally
      significant fear of (re)injury, and (2) a significant lower peak torque of the
      knee flexors. These results are consistent with conditioning models which state
      that pain expectations are associated with a fear response and an urge to avoid
      the pain.

PMID- 8990544
TI  - The assessment of anxiety and fear in persons with chronic pain: a comparison of
      instruments.
AB  - Instruments used to study anxiety and fear responses related to chronic pain vary
      along two dimensions. They differ in terms of the stimuli or situations that
      evoke anxiety responses and the types of anxiety responses included (i.e.
      cognitive, motoric, and physiological). This study examined relations of
      variables from the Pain Anxiety Symptoms Scale (PASS), the Fear-Avoidance Beliefs
      Questionnaire (FABQ), the Fear of Pain Questionnaire (FPQ), and the trait version
      of the Spielberger State-Trait Anxiety Inventory (STAI) with variables related to
      pain severity, perceived disability, and pain behavior. Subjects were 45
      consecutive referrals to a university pain clinic who completed these measures
      during their evaluation. Results suggested that anxiety responses directly
      related to the patient's particular pain sensations are more relevant to the
      understanding of chronic pain than are more general tendencies to respond
      anxiously or fear more varied pain stimuli. Regression analyses showed that
      empirically selected subsets of the anxiety variables predict from 16 to 54% of
      the variance in pain severity, disability and pain behavior. Also, assessment of
      multiple anxiety response types appears useful for understanding pain behavior
      and disability. Further study of fear and anxiety responses of persons with pain
      is likely to benefit from careful selection of measures dependent on the stimulus
      and response dimensions assessed.

PMID- 8990545
TI  - Pathways to fear in spider phobic children.
AB  - Twenty-two children with spider phobia were interviewed about the origins of
      their fear. More specifically, children were asked about conditioning events,
      modeling experiences, and negative information transmission. To evaluate the
      reliability of the information provided by the children, parents were
      independently interviewed about the origins of their children's phobias. While
      46% of the children claimed to have always been afraid, 41% ascribed the onset of
      their fear to aversive conditioning events. The large majority of these events
      were confirmed by parents. These findings cast doubts on a strong version of the
      non-associative account of spider phobia, i.e. the idea that spider phobia is
      acquired in the complete absence of learning experiences.

PMID- 8990546
TI  - Social phobia in disabled workers with chronic musculoskeletal pain.
AB  - The present study assessed the prevalence and impact of social phobia and other
      anxiety disorders in disabled workers with chronic musculoskeletal pain.
      Potential participants were 200 disabled workers consecutively referred to an
      interdisciplinary tertiary care centre. A two stage screening process was used in
      which: (a) a self-report battery was given during a pre-admission visit, and (b)
      pre-planned selection criteria were applied to the self-report instruments to
      select patients for a structured diagnostic interview. Fifty-four of the 146
      patients who provided complete responses on the self-report battery met criteria
      for interview. Twenty-six patients (17.8%) met DSM-IV criteria for a current
      anxiety disorder and, of these, 16 (11.0%) were diagnosed with social phobia.
      Subjects with social phobia rated themselves as having less social support than
      subjects with no psychiatric disorder, but the groups did not differ in pain
      related life interference, personal control, or health care utilization. The
      results suggest that social phobia is over-represented in disabled workers with
      chronic musculoskeletal pain and should be noted as a comorbid condition that may
      compound both suffering and disability.

PMID- 8990547
TI  - Suppression of the emotional Stroop effect by increased anxiety in patients with
      social phobia.
AB  - Anxious individuals are slower at color-naming threat-related than nonthreat
      related words in the emotional Stroop task. Recently, Mathews and Sebastian
      (1993, Cognition and Emotion, 7, 527-530) reported that this Stroop interference
      effect disappears when snake-fearful students are exposed to a snake while
      performing the color-naming task. In the present experiment, we had patients with
      social phobia and normal control subjects perform an emotional Stroop task under
      either low anxiety (i.e. upon entering the laboratory) or high anxiety (i.e.
      before giving a speech). Results indicated that Stroop interference for socially
      threatening words in the phobic group was suppressed under high anxiety. These
      findings may indicate that increased effort enables the subjects to suppress the
      interference produced in the Stroop task.

PMID- 8990548
TI  - Does the Beck Anxiety Inventory measure anything beyond panic attack symptoms?
AB  - The Beck Anxiety Inventory (BAI) has become a popular measure in anxiety
      assessment and the BAI does not overlap in content with measures of depression.
      There is also some factor analytic evidence to support this distinction. However,
      an inspection of the BAI's content indicates that many of its items resemble, or
      are identical to, the symptoms of panic attacks listed in the DSM-IV. Further
      empirical support for this suspicion is provided from the results of a factor
      analysis of the BAI items and the individual DSM-IV panic symptoms contained in
      the Panic Attack Questionnaire, using data from a sample of 157 panic disorder
      patients. A three-factor model (dizziness related, catastrophic cognitions/fear,
      cardiorespiratory distress) emerged that replicated a three-factor model of panic
      symptoms identified in earlier work with another panic disorder sample. All but
      one of the BAI items loaded highly on the three panic symptom clusters and no
      separate BAI factor was obtained. The BAI appears to be confounded with, or
      actually measures, panic attacks rather than anxiety in general. Several
      implications of this finding are discussed.

PMID- 8990549
TI  - The continuing saga.

PMID- 8990550
TI  - Professional metamorphosis.

PMID- 8990551
TI  - MGDS-a worthwhile investment?

PMID- 8990552
TI  - NHS or private--a balanced choice.

PMID- 8990553
TI  - Safety margins for lignocaine local anaesthetic.

PMID- 8990554
TI  - Epileptic fits.

PMID- 8990555
TI  - The male is more dangerous than the female.

PMID- 8990557
TI  - Low fat dietitians.

PMID- 8990558
TI  - The role of dental therapists within the dental team.

PMID- 8990559
TI  - Dental surgeons are first to detect HIV/AIDS.

PMID- 8990560
TI  - Antibiotic prescription for acute dental conditions in the primary care setting.
AB  - To determine the pattern of antibiotic prescribing (source and type) for acute
      dental conditions in the emergency setting, a prospective cross-sectional study
      was undertaken of 500 consecutive new patients attending the examination and
      emergency clinic of the Cardiff Dental Hospital in May 1994. The source and type
      of antibiotics prescribed, the nature of complaint and type of antibiotic
      prescribed in the primary care and dental hospital setting were recorded.
      Antibiotic prescription was a feature of the treatment of 30% (149/500) of
      patients. The 60 patients who had received emergency treatment prior to attending
      the hospital emergency clinic had been prescribed a total of 14 different types
      of antibiotics; 41% of these patients had sought treatment from general medical
      practitioners. Antibiotics were frequently prescribed without generally accepted
      criteria and there was wide variation in prescribing. Overall, only seven
      different types of antibiotics were prescribed in the dental hospital setting.
      The use of second generation antibiotics was more common in general practice than
      in the dental hospital. The results suggest that many patients with dental pain
      may seek treatment from medical practitioners, prior to, or in place of,
      definitive dental treatment. In summary, rationalisation of antibiotic
      prescription and the provision of emergency dental treatment is needed.

PMID- 8990561
TI  - Caries in pre-school children in Camden 1993/94.
AB  - Previous surveys carried out in the inner city area of Camden between 1966 and
      1986 gave indication of a deterioration in dental health in pre-school children
      during the 1980s. Four hundred and six children were included in the current
      survey, which used the same sampling and methodology as previously. The aims of
      the present survey were to determine the current prevalence of caries and of
      rampant caries and to relate prevalence to social factors, to infant feeding
      habits and to the use of sweetened comforters, and to determine the extent of
      dental care received. Caries affected 11% of 2-year-old children and 29% of 3
      year-olds, rampant caries affected 6% and 14% respectively. A higher likelihood
      of caries occurred in children of Asian origin and those given a sweetened
      comforter. For rampant caries, likelihood was greater amongst those of Asian
      origin and those given a sweet drink in a bottle for 2 years or longer.
      Comparison with results of the last study provides little evidence of improvement
      in dental health in young children in this low fluoride area, with a small
      proportion suffering relatively severely from caries.

PMID- 8990562
TI  - Lower third molar treatment planning ability of general dental practitioners and
      oral maxillofacial surgeons using receiver operating characteristics methodology.
AB  - A comparison of lower third molar treatment planning ability of six oral and
      maxillofacial surgeons (three consultants, two senior registrars and one senior
      house officer) and 27 general dental practitioners was carried out using Receiver
      Operating Characteristics (ROC) methodology. Each clinician was presented with
      the same series of 50 case histories and asked to indicate, using a rating scale,
      how certain they were that each lower third molar required removal. These data,
      together with NIH gold standard treatment decisions for each third molar, were
      then used to construct ROC curves for each clinician and, using combined data, to
      produce ROC curves for the groups of hospital specialists and general dental
      practitioners. These curves were then compared statistically. There were
      significant differences between the best and worst practitioners, both in the
      hospital service and within general dental practice. When combined data were
      examined, however, there was no statistical difference in the treatment planning
      ability of hospital specialists and general dental practitioners. These findings
      indicate that lower third molar treatment planning ability is more dependent upon
      individual factors than specialist training. Further, the data presented here
      suggest that general dental practitioners are as capable of treatment planning
      for lower third molars as the specialists to whom they refer.

PMID- 8990563
TI  - Evaluation of a dental practice cardiopulmonary resuscitation training scheme.
AB  - Between 1992 and 1993, 411 members of staff in 50 dental practices were trained
      on site in basic cardiopulmonary resuscitation. Eighteen months after the initial
      training, 25 practices which had been randomly chosen were re-visited to assess
      the staff's residual proficiency. Most of the evaluations made by the staff were
      inadequate, with either omissions or errors in technique when assessing the
      airway, checking for breathing, or for the presence of a pulse. There were also
      prolonged delays in the resuscitations, and the mean number of ventilations and
      compressions that were given were too few, and most were incorrect. Overall, the
      results lend further support to the concept of periodical supervised re-training.

PMID- 8990564
TI  - The presentations and management of transposed teeth.
AB  - Tooth transposition is an uncommon dental anomaly that nevertheless has important
      implications regarding treatment. This article describes six types of
      transposition, discussing the problems and possible solutions. It is important to
      ensure that the results of any treatments for transposition are both aesthetic
      and functional.

PMID- 8990565
TI  - Substance use among rural secondary schools in Zimbabwe: patterns and prevalence.
AB  - OBJECTIVE: To survey drug use among rural secondary school students. DESIGN: Self
      reported questionnaires developed by the World Health Organisation and translated
      into Shona were distributed to randomly selected students from 36 schools.
      SETTING: Nyanga District secondary schools, Zimbabwe. SUBJECTS: 1,000 secondary
      school students, males and females, forms one to six. MAIN OUTCOME MEASURES:
      Demographic variables, prevalence rates, frequency of drug use, first time usage,
      breakdown by age, sex and school type. RESULTS: Alcohol was the commonest "ever
      taken" substance (34.9pc), followed by tobacco (18.5pc), solvents (6.9pc) and
      cannabis (34.9pc). Frequency of use was low and use of other categories of drugs
      was negligible. CONCLUSIONS: Appropriate educational programmes need to be
      formulated and tailored to meet the needs of rural adolescents.

PMID- 8990566
TI  - Comparison of the Omron HEM-713C automated blood pressure monitor with a standard
      ausculatory method using a mercury manometer.
AB  - OBJECTIVES: To compare the Omron HEM-713C automated blood pressure machine with
      the standard ausculatory method using a mercury manometer. DESIGN: Blood
      pressures of randomly selected subjects were measured using both the Omron HEM
      713C and the mercury manometer. SETTING: Dombotombo surburb in Marondera,
      Zimbabwe. SUBJECTS: One hundred and sixteen subjects 25 years and above (47 males
      and 69 females) randomly selected in Marondera. MAIN OUTCOME MEASURE: Systolic
      blood pressure and diastolic blood pressure. RESULTS: The Omron HEM-713C passed
      with a grade B for both systolic and diastolic blood pressures when using the
      British Hypertension Society protocol. It also passed both systolic and diastolic
      criteria for Association of the Advancement of Medical Instrumentation.
      CONCLUSION: The Omron HEM-713C compares well with the standard mercury manometer,
      we therefore recommend its use in both research and clinical applications which
      require blood pressure measurements.

PMID- 8990567
TI  - Maternal human immunodeficiency virus infection and pregnancy outcome.
AB  - OBJECTIVE: A longitudinal study to determine the natural history of HIV-1
      infection in pregnancy, infancy and early childhood was carried out in Ndola,
      Zambia. DESIGN: Prospective study. SETTING: Kabushi and Chifubu clinics.
      SUBJECTS: A total of 965 women attending antenatal care were screened for anti
      HIV antibodies using the Welcozyme test. All reactive sera were confirmed by
      Western Blot. One hundred and fifty seropositive pregnant women (cases) with
      their age and parity matched pregnant control (seronegative) were recruited into
      the study. They were followed up through delivery. MAIN OUTCOME MEASURE: personal
      characteristics, socio-economic and other risk factors. RESULTS: The prevalence
      of anti HIV-1 antibodies among the 965 women was 15.5pc. Results of baseline data
      between the two groups of women indicate significant differences (p < 0.05) in
      the following variables; marital status, outcome of last pregnancy, whether last
      child is still alive, history of herpes zoster, lymphadenopathy, dermatitis, oral
      thrush and mean haemoglobin level. There were no differences in the incidence of
      abortions, stillbirths and neonatal deaths. However, the mean birth weight of
      babies born out of seropositive women was significantly lower than babies of
      seronegative women. CONCLUSION: It is concluded that HIV-1 infection in pregnancy
      is associated with low birth weight.

PMID- 8990568
TI  - Missed opportunities for vaccination in Chitungwiza, Zimbabwe 1995: a service
      deficiency which can easily be eliminated.
AB  - OBJECTIVES: Missed opportunities for vaccination occur when a child or woman who
      is eligible for a vaccination visits a health facility but fails to receive that
      vaccination. Our study attempted to determine the extent and reasons for missed
      opportunities occurring in an urban setting in Zimbabwe. DESIGN: This study was
      carried out using the standard WHO EPI protocol for ascertaining missed
      opportunities for vaccination. SETTING: All four health clinics in Chitungwiza
      City. SUBJECTS: All appropriate clients (children < 2 years and women of
      childbearing age) exiting each facility. RESULTS: The study revealed a global
      missed opportunity rate of six pc for children and 55pc for women of childbearing
      age. Missed opportunities occurred more frequently when children attended
      curative services and when women of childbearing age attended preventive
      services. CONCLUSIONS: Vaccination services can be improved by making all
      vaccines available and by screening children and women at all contacts with
      health services. Additionally, all women should receive and be encouraged to
      carry a tetanus toxoid vaccination card when visiting a health facility. In all
      cases, a vial of vaccine should be opened even if only one child or woman is
      eligible for vaccination, in accordance with Ministry of Health policy.

PMID- 8990569
TI  - Maternal risk factors for childhood malnutrition in the Mazowe District of
      Zimbabwe.
AB  - OBJECTIVE: To determine the maternal risk factors associated with childhood
      malnutrition. DESIGN: An unmatched case control study of 327 children < 5 years
      of age. SETTING: Primary health care clinics on the communal lands and commercial
      farms in the Mazowe District of Zimbabwe. MAIN OUTCOME MEASURES: The relationship
      between maternal risk factors and childhood malnutrition was analysed. To correct
      for confounding variables a forward stepwise logistic regression was performed.
      RESULTS: Odds ratio (95pc confidence limits) for childhood malnutrition were a
      working mother 5.69 (2.37 to 3.66) and lack of decision making power 2.86 (1.1 to
      7.45) on the communal lands, and lack of extra income generating projects 3.92
      (1.64 to 9.54) and previous death of a child 2.17 (1.08 to 4.39) on the
      commercial farms. In both areas malnutrition was associated with < or = 1 acre of
      land 3.66 (1.4 to 9.53) and p < 0.01 (Fisher's exact test) for the communal lands
      and commercial farms respectively), and father's income < or = Z$150/month 12.5
      (2.5 to 100) and 5.56 (1.4 to 25.0) for the communal lands and commercial farms
      respectively. CONCLUSIONS: To reduce childhood malnutrition in the rural areas
      reduced maternal work load and increased decision making power, better access to
      health care plus more access to land and higher income are all critical issues.

PMID- 8990570
TI  - Scope of urinary pathogens isolated in the Public Health Bacteriology Laboratory,
      Harare: antibiotic susceptibility patterns of isolates and incidence of
      haemolytic bacteria.
AB  - OBJECTIVES: To determine the scope of urinary pathogens isolated in the Public
      Health Bacteriology Laboratory, their antibiotic susceptibility patterns and the
      incidence of haemolytic bacteria in Harare. DESIGN: Prospective study. Patients
      of different age groups attending various clinics in Parirenyatwa Hospital,
      Harare, between October 1995 and April 1996 were enrolled for the study. SETTING:
      A laboratory based study at the Bacteriology Unit, Public Health Laboratories,
      Harare. SUBJECTS: 1,760 urine specimens obtained from male and female patients
      suspected of having UTI. RESULTS: Out of a total number of 1,760 urine specimens
      screened only 473 (26.9pc) were positive for UTI pathogens. Four hundred and
      nineteen (88.5pc) and 46 (9.7pc) of the 473 positive UTI pathogens were Gram
      negative and Gram positive bacteria respectively. Eight (1.7pc) of the positive
      isolates were Candida spp. The commonest pathogen isolated was Escherichia coli
      (40.5pc), followed by Klebsiella spp. (22.1pc) and Proteus spp. (7.2pc). Of the
      positive isolates 184 (38.9pc) and seven (1.5pc) were beta- and alpha-haemolytic
      respectively. Of E. coli isolates 72pc were beta-haemolytic. Sex distribution
      showed that 53pc and 47pc of the UTI pathogens were isolated from males and
      females respectively. E. coli was more predominant in females (51.3pc).
      Antibiotic susceptibility patterns revealed that 100pc of strains of E. coli,
      Proteus spp., Serratia spp., Salmonella spp., Morganella spp., Staphylococcus
      aureus and coagulase negative staphylococci (CNS) were sensitive to
      Ciprofloxacin. Urinary isolates were markedly resistant to Tetracycline,
      Carbenicillin, Cotrimoxazole, Ampicillin and Nitrofurantoin. Fusidic acid and
      Clindamycin were active against staphylococcal species. CONCLUSION: We conclude
      that E. coli is the commonest UTI pathogen and that 72pc of strains were beta
      haemolytic. We suggest the use of Ciprofloxacin as the drug of choice for the
      treatment of UTI caused by both Gram positive and Gram negative UTI pathogens.
      Nitrofurantoin and Gentamycin are in addition recommended for E. coli while
      Fusidic acid and Clindamycin may be useful for staphylococcal species.

PMID- 8990571
TI  - Bacteriological studies of dental caries in Ile-Ife, Nigeria.
AB  - To determine the relationship between bacterial colonization of tooth surfaces
      and dental caries, selective agar media-MM10 Sucrose, Rogosa SL and Blood agar
      were used to isolate bacteria from the scrappings of 60 tooth surfaces of 30
      children and young adults. Mean age +/- SD was 13.3 +/- 4.1 (range seven to 19
      years). Streptococcus mutans was isolated from 36 surfaces representing 60pc
      Lactobacillus species from 38 surfaces (68pc), and Actinomyces species from 12
      surfaces (20pc). The individual prevalences of these organisms decreased with
      age. The distribution of bacteria according to surfaces examined showed that the
      pits and fissures were the main habitat of Streptococcus mutans and Lactobacilli
      were sensitive to erythromycin. Actinomyces species were 100pc sensitive to
      Penicillin. All the bacteria species isolated were also found to be 100pc
      sensitive to Olfoxacin (Tarivid). It is suggested that the use of antibiotics may
      stop the growth of cariogenic bacteria in individuals and thereby contribute to a
      decline in the incidence and prevalence of dental caries in the community.

PMID- 8990572
TI  - A three year clinical review of the impact of angiotensin converting enzyme
      inhibitors on the intra hospital mortality of congestive heart failure in
      Nigerians.
AB  - Angiotensin converting enzymes inhibitors are now regarded as the cornerstone of
      congestive heart failure therapy owing to established reduction in mortality and
      the symptomatic amelioration following their use. Although the response to
      converting enzyme inhibitor therapy may be influenced by race, we have reported a
      trend to reduce intra hospital mortality, the correction of hyponatremia and
      shortened hospitalization in Nigerians treated with converting enzyme inhibitors.
      We have now conducted an extended retrospective study, to evaluate the trends in
      the use of enalapril or captopril and its impact on prognosis in Nigerian
      patients with heart failure alone, admitted between January 1992 to December
      1994. The proportion of heart failure treated with (captopril or enalapril)
      increased from 37pc in 1992, to 50pc in 1993, to 65pc in 1994. The demographic
      variables and cause of heart disease were similar in patients treated with
      converting enzyme inhibitors (n = 55) and those treated conventionally (n = 36).
      The cumulative mortality among converting enzyme inhibitors treated patients, was
      (8/55, 14pc) compared to patients not treated (17/36, 48pc) x2 = 12.4; p <
      0.0001. There was no sex predilection in mortality (M = 25pc, F = 28pc, mean
      27pc). However, initial serum Na+,125mmol was significantly (x2 = 11.1; p <
      0.001) more common in the dead patients, 25pc compared to the survivors
      discharged home 7.5pc. The median hospital stay was 17 days in captopril treated
      survivors (range two to 44 days) and 19 days (range four to 67 days) in
      conventionally treated patients. Thus converting enzyme inhibitor therapy may
      reduce intra hospital mortality in Black Africans hospitalized for congestive
      heart failure and shorten hospital stay, despite the epidemiologically low plasma
      renin in Blacks. Hyponatremia may be a poor prognostic index in heart failure in
      our patients, and its reversal by converting enzyme inhibitors may reflect
      neurohormonal inhibitor. Earlier and more wide spread use of angiotensin
      converting enzyme inhibitors in Nigerian and Black Africans with chronic heart
      failure is now clearly indicated.

PMID- 8990573
TI  - Risk factors for outbreaks of infectious intestinal disease linked to domestic
      catering.
AB  - The epidemiology of general outbreaks of infectious intestinal disease associated
      with domestic catering for large numbers is described and compared with foodborne
      outbreaks in other settings. From 1 January 1992 to 31 December 1994, the PHLS
      Communicable Disease Surveillance Centre identified 101 foodborne general
      outbreaks of infectious intestinal disease associated with domestic catering in
      England and Wales (16% of all foodborne outbreaks). Salmonella species were
      associated with 77 of the 101 outbreaks and S. enteriditis phage type 4 accounted
      for 57. Small round structured viruses were implicated in five outbreaks,
      Clostridium perfringens in four, Bacillus cereus in two, and Campylobacter sp and
      Escherichia coli in one each. No pathogen was identified in 11 outbreaks.
      Outbreaks occurred most commonly in summer. The commonest vehicles implicated
      were poultry/eggs in 44 outbreaks, desserts in 13, and meat/meat products in
      nine. Salad/vegetables, sauces, and fish/shellfish were each implicated in eight
      outbreaks. Raw shell eggs were implicated in a fifth of outbreaks. Inappropriate
      storage was the commonest fault, reported in association with 50 outbreaks
      (ambient temperature for long periods before serving in 29), inadequate heat
      treatment was reported in 35, cross contamination in 28, an infected food handler
      in 11, and other faults in 14. Outbreaks associated with catering on domestic
      premises were independently more likely than outbreaks in other settings to be
      associated with salmonellas, inappropriate storage of food, and consumption of
      poultry, eggs, or sauces. Public health services need to direct messages about
      the use, preparation, and storage of food to those who cater on domestic
      premises.

PMID- 8990575
TI  - Food poisoning among clients of a meals on wheels service.
AB  - Sixty-one out of 105 elderly people who received a meal from a meals on wheels
      service developed a diarrhoeal illness. Twenty-seven of the 61 were admitted to
      hospital and three died. Epidemiological evidence suggested that food poisoning
      was associated with eating strawberry mousse made with raw eggs. Salmonella
      enteritidis phage type 4 was identified as the causative organism.

PMID- 8990574
TI  - Marshmallows cause an outbreak of infection with Salmonella enteritidis phage
      type 4.
AB  - Thirty-six cases of Salmonella enteritidis phage type (PT) 4 infection, mainly in
      children, were notified in one local authority in the two weeks beginning on 23
      October 1995. Twenty-four cases and 42 controls nominated by cases were included
      in a case control study, which showed a significant association between illness
      and the consumption of marshmallow confectionery from a bakery. S. enteritidis
      PT4 was isolated from samples of the marshmallow, and all isolates had the same
      plasmid and pulsed field gel electrophoresis profiles. The marshmallow had been
      made using raw egg white, which shows that not all caterers follow the Department
      of Health's advice.

PMID- 8990576
TI  - An outbreak of viral gastroenteritis on a cruise ship.
AB  - Three hundred and seventy-eight passengers reported gastroenteritis during four
      cruises in the western Mediterranean on consecutive weeks of 1995. The rate at
      which cases were reported each day increased on the fourth cruise. The ship's
      owner commissioned an epidemiological investigation from the PHLS Communicable
      Disease Surveillance Centre. Cases reported explosive vomiting and diarrhoea,
      which lasted from 24 hours to five days, and were suggestive of viral
      gastroenteritis. No food handlers reported illness, but enquiries suggested that
      some had been ill and treated themselves. No bacterial pathogens were isolated
      from faecal specimens provided by cases or from water, food, and environmental
      samples taken from the galley. Small round structured viruses (SRSV) were
      identified by reverse transcriptase polymerase chain reaction in two faecal
      specimens and one specimen of vomit from people who became ill during the fourth
      cruise. SRSV was also identified in one faecal specimen by electron microscopy.
      Environmental inspection revealed inappropriate food handling, hygiene, and
      storage. During one 24 hour period no chlorine was detectable in the water. A
      case control study conducted on the fourth cruise sought details of exposure to
      various foodstuffs, unbottled water, and various parts of the ship. No
      significant associations were found between illness and any exposures. The
      evidence strongly suggested a continuing outbreak of SRSV infection transmitted
      from person to person. Some passengers remained on board for a second week and
      could have transmitted their infection to new arrivals. The ship was cleared and
      disinfected at the end of the fourth cruise in order to interrupt transmission.
      Fewer than 10 cases presented in each of the fifth and sixth cruises.

PMID- 8990577
TI  - AIDS and severe HIV disease: combined predictions for the United Kingdom to 1999.
AB  - The number of HIV infections prevalent in the United Kingdom (UK) at the end of
      1994 have been estimated. Estimates of the future annual incidence and prevalence
      of AIDS and severe HIV disease have been calculated for the UK by combining
      recently published projections for Scotland with projections produced for England
      and Wales adjusted to account for Northern Ireland. The number of HIV infections
      prevalent in the UK at the end of 1994 was estimated to be about 23,000, 36% of
      them undiagnosed. It was estimated that 52% of prevalent infections were in
      homo/bisexual men, and 32% were in people exposed through heterosexual
      intercourse. Between 2100 and 2190 new cases of AIDS are expected to be reported
      in the UK each year from 1995 to 1999. It is predicted that a 30% rise in the
      number of cases exposed through heterosexual intercourse and a 17% rise in cases
      who inject drugs will be balanced by a 7% fall in cases among homo/bisexual men.
      Prevalent AIDS cases in the UK are expected to rise by 15%, from 3740 at the end
      of 1995 to 4290 at the end of 1999. The number of people expected to be living
      with severe HIV disease, including AIDS, will also rise by about 15%, from 7545
      at the end of 1995 to 8650 at the end of 1999.

PMID- 8990578
TI  - Outbreaks of influenza and a rise in respiratory syncytial virus: winter has
      arrived.

PMID- 8990579
TI  - World AIDS Day, 1 December 1996.

PMID- 8990580
TI  - Outbreak of meningococcal disease in students in Cardiff.

PMID- 8990581
TI  - Polymerase chain reaction for the diagnosis of meningococcal disease.

PMID- 8990582
TI  - Touching the third rail: time to return the retirement age for early Social
      Security benefits to 65.

PMID- 8990583
TI  - Internet resources on aging: ten top Web sites.

PMID- 8990584
TI  - Ten years later: what have we learned about human aging from studies of cell
      cultures?
AB  - Human cells in culture have been used for over 30 years as models to examine the
      biology of aging. Some studies suggest that cellular aging is a genetically
      dominant characteristic; other studies suggest that aging is characterized by a
      general dysregulation of processes and pathways. A question of major interest is
      to what extent replicative senescence in culture provides insights about
      senescence in the organism. Overall, the findings suggest that there may be
      multiple cellular pathways to acquiring the senescent phenotype, some more
      relevant to organismic aging than others. Nevertheless, by studying processes in
      cell cultures that are known to fail in aging, we can learn the cellular and
      molecular bases of these failures.

PMID- 8990585
TI  - Theoretical developments in the psychology of aging.
AB  - This article presents a summary overview of the most distinctive psychological
      theories of aging since World War II. Theoretical developments are broadly
      classified into three periods, respectively: The Classical period ('40s-'70s),
      represented by Developmental Tasks/Activity Theory, Psychosocial Theory of
      Personality Development, Counterpart Theory, Disengagement/Activity Theory,
      Personality Theory of Age and Aging, and Cognitive Theory of Personality and
      Aging; the Modern period ('70s-'90s), which includes theories on Life-span
      Development and Aging, Reduced Processing Resources, Personality and Aging,
      Behavioral Genetics and Aging; and the New period ('80s-'90s), represented by
      Gerotranscendence and Gerodynamics/Branching Theory. The overview ends with an
      outlook on psychogerontological theorizing.

PMID- 8990586
TI  - Tracing the course of theoretical development in the sociology of aging.
AB  - The emergence of sociological theorizing in the field of aging is described as a
      sequence of two transformations in gerontological thinking. Each transformation
      signals a principal change in the conception of the nature and practice of
      gerontological inquiry. The first transformation was marked by Cumming and
      Henry's book Growing Old: The Process of Disengagement (1961), in which a formal
      theory of aging is laid out for the first time by social scientists. This set the
      stage for the development of a range of alternative theoretical challenges. There
      is a second transformation that began in the late 1970s and early 80s which
      involved not so much the recognition of theory as a reflection of that
      recognition itself, being metatheoretical. The issues raised represented a
      fundamental concern with the so-called "facts" of aging themselves, focusing on
      the socially constructive and ideological features of age conceptualizations
      social phenomenological and Marxist concerns, respectively. More recently (in the
      late 1980s and early 90s), social gerontologists have turned to critical theory
      and feminist perspectives to also examine these issues.

PMID- 8990587
TI  - The burden of aging: a theoretical framework for understanding the shifting
      balance of caregiving and care receiving as cohorts age.
AB  - Unless changes occur in the way cohorts age, the future aging of the population
      will make the burden of caring for older persons an increasingly salient
      political issue in American society. There is no reason, however, why aging in
      the future should replicate the pattern of aging that currently exists. A helpful
      step toward understanding what social changes would reduce the burden that aging
      cohorts place on society is the development of aging theory. This article
      develops a theoretical framework that explicates factors determining the level of
      care given and care received by cohorts moving through different stages of later
      life. Four proximate determinants of caregiving and three proximate determinants
      of care receiving are specified. Once the proximate determinants are identified,
      attention is focused on social changes that could reduce the burden of aging
      produced by cohorts aging through later life in the future.

PMID- 8990588
TI  - Progress and pitfalls in gerontological theorizing.
AB  - Since 1988, there has been a commendable increase in concern for explicit theory
      development in gerontology. However, this has not been reflected in recent
      journal articles reporting empirical research. We summarize some central issues
      in the recent history of gerontological theory-building, noting both "progress"
      and "pitfalls." Have there been paradigmatic shifts in biogerontological, psycho
      gerontological, and social-gerontological theories of aging during the past
      decade? We think not, though advocates of particular theoretical perspectives may
      disagree.

PMID- 8990589
TI  - Rectangularization of the survival curve in The Netherlands, 1950-1992.
AB  - In this article we determine whether rectangularization of the survival curve
      occurred in the Netherlands in the period 1950-1992. Rectangularization is
      defined as a trend toward a more rectangular shape of the survival curve due to
      increased survival and concentration of deaths around the mean age at death. We
      distinguish between absolute and relative rectangularization, depending on
      whether an increase in life expectancy is accompanied by concentration of deaths
      into a smaller age interval or into a smaller proportion of total life
      expectancy. We used measures of variability based on Keyfitz' H and the standard
      deviation, both life table-based. Our results show that absolute and relative
      rectangularization of the entire survival curve occurred in both sexes and over
      the complete period (except for the years 1955-1959 and 1965-1969 in men). At
      older ages, results differ between sexes, periods, and an absolute versus a
      relative definition of rectangularization. Above age 60 1/2, relative
      rectangularization occurred in women over the complete period and in men since
      1975-1979 only, whereas absolute rectangularization occurred in both sexes since
      the period of 1980-1984. The implications of the recent rectangularization at
      older ages for achieving compression of morbidity are discussed.

PMID- 8990590
TI  - The oldest man ever? A case study of exceptional longevity.
AB  - This article summarizes recent findings in a case study of exceptional longevity.
      CM, a resident of San Rafael, California, was 114 years old in August 1996. He is
      the first properly verified case of a 114-year-old man in human history (although
      a few women have been known to live longer). Our investigation of CM continues as
      we attempt to gather additional information about his life, family history, and
      current condition. Here, we consider only two aspects of this case: its
      authenticity and its significance in the history of human longevity. We believe
      that we have proven that CM's stated age is accurate. Based on the available
      information, it also seems a reasonable conjecture that he may be the oldest man
      alive today and perhaps the oldest man who has ever lived. This study documents
      an extreme example of human longevity and records characteristics of the man's
      life that may provide clues about the causes of his exceptional survivorship.

PMID- 8990591
TI  - Who takes early Social Security benefits? The economic and health characteristics
      of early beneficiaries.
AB  - Using the 1992 and 1994 Waves of the Health and Retirement Survey, we compare
      individuals who first take Social Security benefits at age 62 with those who
      don't and find that the income and net assets of these two groups are similar in
      the years just prior to eligibility. However, there is great diversity within the
      groups, so that poor health appears to be more closely related to lower economic
      well-being than is early Social Security acceptance status. Our results suggest
      that raising the Social Security retirement age is not likely to dramatically
      lower the economic well-being of the typical person aged 62 since only 3% of men
      aged 62 are receiving Social Security retirement benefits, are in poor health,
      and have Social Security retirement benefits as their only source of pension
      income.

PMID- 8990592
TI  - Can Medicaid long-term care expenditures for the elderly be reduced?
AB  - During 1995 and 1996 Congress debated numerous proposals that would dramatically
      reduce the rate of growth in Medicaid spending, initiatives that inevitably would
      affect long-term care for the elderly. There are three broad strategies that
      states might use to control long-term care spending-bring more private resources
      into the long-term care system to offset Medicaid's expenditures, reform the
      delivery system so that care can be provided more cheaply, and reduce Medicaid
      eligibility, reimbursement, and service coverage. Based on the available research
      evidence, there is little evidence to suggest that large savings are possible
      without adversely affecting beneficiaries' eligibility, access to services, and
      quality of care received.

PMID- 8990593
TI  - Caregiving and women's Social Security benefits: a response to Sandell and Iams.

PMID- 8990594
TI  - "What will happen to my child when I'm gone?" A support and education group for
      aging parents as caregivers.
AB  - This article describes the rationale, design and implementation of a support and
      education group for parents caring for disabled children in later life. In a
      supportive and informative environment, parents found peers facing similar
      challenges relating to the provision of care in light of their own aging, a
      lifetime of caregiving, and their concerns about their children's futures. The
      experience of this group intervention strategy provides insight into the needs
      and strengths of this neglected segment of the caregiving population and suggests
      implications for future research and practice.

PMID- 8990595
TI  - The InterpreCare System: overcoming language barriers in long-term care.
AB  - Differences in the language spoken by residents and staff in long-term care
      create a variety of problems. The InterpreCare System represents an intervention
      for dealing with this issue. We describe the nature and purpose of this
      intervention, and provide detailed instructions on the construction of Language
      Boards. Examples are given from our experience at Menorah Park Center for the
      Aging in enabling English-speaking staff to use Russian phrases while delivering
      care. Beneficial effects produced by the intervention are discussed.

PMID- 8990596
TI  - Wolff Award 1996. The actions of valproate and neurosteroids in a model of
      trigeminal pain.
AB  - Gamma-aminobutyric acid (GABA) receptors are ubiquitous inhibitory receptors in
      the central and peripheral nervous systems. Valproic acid (2-propylpentanoic
      acid), which enhances GABA synthesis and blocks degradation, is useful in
      migraine treatment and may act through activation of GABA receptors to modulate
      trigeminal nociceptive neurons innervating the meninges. To investigate this
      possibility, we tested the effect of valproate and allopregnanolone, a metabolite
      of progesterone, which binds and modulates the GABA receptor in an animal model
      of cephalic pain. One hundred ten Hartley guinea pigs were pretreated with either
      valproate or allopregnanolone 30 minutes prior to activation of trigeminal
      afferent fibers via intracisternal injection of the irritant, capsaicin. The
      effects of valproic acid and allopregnanolone were examined on c-fos expression
      within the trigeminal nucleus caudalis (lamina I, II), the termination site for
      small unmyelinated C fibers projecting from the meninges. C-fos positive cells
      were counted at three representative levels (rostral, middle, and caudal) by an
      observer naive to the treatment group. We found that valproate (> or = 10 mg/kg,
      IP) reduced labeled cells by 52% (P < 0.05) and allopregnanolone (> or = 100
      mg/kg, IP) reduced labeled cells by 42% (P < 0.01). Bicuculline (GABAA
      antagonist), but not phaclofen (GABAB antagonist), blocked the valproate effect,
      thereby documenting the importance of GABAA receptors. We conclude that the
      attenuation of c-fos-LI by valproate and allopregnanolone is mediated via GABAA
      receptors. These studies complement prior experiments showing that valproic acid
      and allopregnanolone block neurogenic inflammation within the meninges via GABAA
      receptor-mediated mechanisms. The findings suggest a potential strategy for
      discovering new antimigraine drugs with high affinity for the GABAA receptor and
      its modulatory sites.

PMID- 8990597
TI  - Migraine patients show increased platelet vasopressin receptors.
AB  - This study was designed to investigate vasopressin receptor status (Bmax and Kd)
      on platelets, vasopressin plasma levels, and vasopressin-induced platelet
      aggregation in migraine patients (21 females and 6 males) during a headache-free
      interval and in a matched control group. In the migraine group, Bmax was
      significantly higher (P = 0.02) at 53.9 +/- 20.6 fmol/mg than in the control
      group (36.8 +/- 21.0 fmol/mg). A correlation between Bmax and high or low
      sensitivity to vasopressin as an aggregator was evident in the control group, but
      not in the migraine group. No differences in Kd or in plasma levels of
      vasopressin between the migraine and control group were apparent. Men in both
      groups were much less sensitive to vasopressin as a platelet aggregator than were
      women (P < 0.01). Whether the higher Bmax in the migraine group is a reflection
      of temporarily higher vasopressin levels during headache or reflects a primary
      increase in sensitivity to vasopressin, remains to be clarified. The higher
      sensitivity of platelets (as a model for vessel wall receptors) from women may
      indicate why many more women than men suffer from migraine. Since the Bmax of the
      vasopressin receptor on platelets from migraine patients is increased compared to
      controls, treating migraine headache with vasopressin may deserve more attention.

PMID- 8990598
TI  - Acetazolamide testing of cerebral vasodilator capacity provokes "vascular" but
      not tension headaches.
AB  - Cerebrovascular capacitance was tested by measuring local cerebral blood flow
      (LCBF) by xenon-contrasted CT scanning before and after the oral administration
      of 14.3 mg/kg of acetazolamide among 45 subjects including 15 age-matched
      controls without history of headache, 20 migraineurs with and without aura, 3
      patients with cluster headache, and 7 patients with tension-type headache.
      Percentage increases of LCBF were measured in 10 regions located throughout both
      hemispheres. Laterality indices for asymmetric LCBF increases were calculated.
      Local cerebral blood flow in cortical gray matter increased 5.9% in controls,
      9.9% in patients with tension headaches, but 18.6% in both migraine and cluster
      headache patients; significantly greater LCBF increases than among controls or
      among patients with tension headaches (P < 0.05). Increases in LCBF were
      significantly asymmetric among migraine and cluster patients and provoked typical
      unilateral vascular headaches which responded to sumatriptan. Maximal asymmetric
      LCBF increases also corresponded to the reported side of the induced headaches
      confirming their vascular pathogenesis. Patients with tension headaches and
      controls without history of headache did not develop head pain after
      acetazolamide.

PMID- 8990599
TI  - Relative contributions of life events versus daily hassles to the frequency and
      intensity of headaches.
AB  - This study investigated headaches parameters (frequency and intensity) in
      relation to (the number and severity of) two types of psychosocial stress: major
      life events (as assessed by a revised Social Readjustment Rating Scale) and minor
      daily hassles (as assessed by a revised Hassles Scale). Subjects were 261
      volunteers reporting headache. Results revealed that both headache frequency and
      intensity were significantly predicted by daily hassles, in particular, the
      average severity of these hassles, but there was a negligible relationship
      between headache parameters and any of the life event measures. Furthermore, a
      significant relationship emerged between life events and daily hassles
      themselves. This fits with recent findings that life events (while exerting
      little direct effect on headache) may trigger a succession of hassles which
      culminate in headaches. Also, it is not the number of hassles, but the perceived
      severity of these hassles that best predicts headache frequency and intensity.
      Finally, though significant as predictors, daily hassles explained a small
      portion of the variance in headache, thus pointing to the host of other possible
      biological and psychosocial contributions to headache.

PMID- 8990600
TI  - Evaluation of beta-endorphin secretion in patients suffering from episodic
      cluster headache.
AB  - In order to obtain data regarding peripheral levels of beta-endorphin in head
      pain syndromes, we evaluated the plasma beta-endorphin secretory pattern in 12
      adult male patients suffering from cluster headache. Blood samples were drawn
      every 2 hours for a 24-hour period, and in addition at 30-minute intervals for
      120 minutes during cluster attacks. The same sampling was repeated during an
      asymptomatic period. Cluster headache patients showed no significant beta
      endorphin circadian rhythm and a delayed acrophase during cluster periods
      compared with that recorded in the remission period and in normal subjects.
      Eighteen cluster headache attacks were recorded during the study day, 13 (72%) of
      which were followed by a significant increase in beta-endorphin levels. No
      correlation was found between beta-endorphin maximum net increase and intensity
      and/or duration of pain. These data suggest the hypothesis of a temporary
      alteration of beta-endorphin circadian secretion, probably related to involvement
      of neural structures controlling biorhythm pacemakers.

PMID- 8990601
TI  - Cluster headache is an inherited disorder in some families.
AB  - We investigated the familial occurrence of cluster headache in 370 probands with
      cluster headache, diagnosed according to the operational diagnostic criteria of
      the international Headache Society. Seven probands belonged to three families. A
      positive family history of cluster headache was found in 7% (25 of 366) of the
      families. Compared with the general population, the first- and second-degree
      relatives of the 370 probands with cluster headache had a 14- and 2-fold
      increased risk of having cluster headache, after standardization for sex and age.
      This increased familial risk strongly suggests that cluster headache has a
      genetic cause. The patterns of segregation were assessed by complex segregation
      analysis performed with the computer program, POINTER. The segregation analysis
      suggests that cluster headache has an autosomal dominant gene with a penetrance
      of 0.30 to 0.34 in males and 0.17 to 0.21 in females. The gene is present in 3%
      to 4% of males and 7% to 10% of females with cluster headache.

PMID- 8990602
TI  - Effects of headaches during neuropsychological testing of mild head injury
      patients.
AB  - The Luria-Nebraska Neuropsychological Battery (LNNB) and the Minnesota
      Multiphasic Personality Inventory (MMPI) were administered to 37 mild head injury
      patients, whose headache activity was rated at the time of testing. A one-way
      analysis of variance (ANOVA) compared each of the 11 LNNB scores of patients with
      severe headache, mild headache, and no headache. The results revealed no
      significant differences on varied neuropsychological tests between the three
      headache groups. Similar analyses of the 13 MMPI scores also indicated no
      significant differences between the three headache groups across various
      psychoemotional measures. The results are consistent with previous research and
      suggest that headaches do not affect the performance of mild head injury patients
      on varied neuropsychological tests requiring concentration and immediate memory,
      but because of the small number of patients in this study the findings should be
      considered tentative.

PMID- 8990603
TI  - Frequency of magnetic resonance imaging abnormalities in patients with migraine.
AB  - BACKGROUND: The frequency of magnetic resonance imaging (MRI) abnormalities in
      patients with migraine has been reported at 12% to 46%. We examined a series of
      patients to determine the frequency of MRI abnormalities, and any relationship of
      frequency with patient age, sex, migraine type, duration of symptoms, and other
      medical conditions. METHODS: Magnetic resonance imaging findings were reviewed
      retrospectively with respect to presence of focal white matter hyperintensities
      in 185 consecutive patients. Patients had been diagnosed with migraine by a
      neurologist. All images had been interpreted by a neuroradiologist. Clinical
      information was obtained by chart review. RESULTS: Sixteen percent had focal
      white matter abnormalities. Among patients less than 50 years old, and without
      other medical problems such as hypertension, atherosclerotic heart disease,
      diabetes mellitus, autoimmune disorder or demyelinating disease, only 6% had
      white matter abnormalities. Increased frequency of white matter abnormalities was
      associated with age and medical risk factors, but not with sex, migraine subtype,
      or duration of migraine symptoms. CONCLUSION: The observed frequency of MRI
      abnormalities in our series is lower than has been previously reported. In many
      cases, these abnormalities may be unrelated to migraine. When such changes are
      discovered in a patient with migraine, other etiologies should be considered.

PMID- 8990604
TI  - SUNCT syndrome. Statuslike pattern.
AB  - Four SUNCT patients with a clinical "SUNCT status" witnessed by the investigators
      are reported. Such an extreme aggregation of typical attacks lasting for the
      better part of the day, 1 to 3 days in a row has not previously been observed.
      Appropriate supplementary examinations ruled out an intracranial lesion in all
      four patients. Indeed, an observation period of more than 5 years speaks against
      a symptomatic etiology of SUNCT in these cases. Although rarely seen, clinical
      status may be a feature of the SUNCT syndrome.

PMID- 8990605
TI  - Atenolol prophylaxis in migraine secondary to an arteriovenous malformation.
AB  - The migrainous syndrome secondary to a parieto-occipital arteriovenous
      malformation usually presents as unilateral headache with visual aura of
      progressive severity. We report successful prevention by atenolol of migraine
      with visual aura associated with an occipital vascular malformation. Effectively
      preventing migraine delayed specific therapeutic measures, thereby exposing the
      patient to the risk of an intracranial hemorrhage. The authors consider that
      prophylactic therapy should not be started whenever such an association is
      suspected.

PMID- 8990606
TI  - Turnaround time of in-patient discharge letters: a simple system of audit.
AB  - This user-friendly audit system, successfully developed and implemented in a
      district general hospital for use across all clinical specialties, is able to
      calculate the turnaround time of final discharge letters and as a consequence
      identify any areas of delay between patients' discharge and the letter being
      mailed. By serially monitoring both individual consultant and specialty
      performance, the system can provide valuable information on the discharge letter
      process to Purchaser and Provider alike. A copy of the audit system together with
      details of audit design and methodology is available to interested clinicians,
      managers and audit facilitators.

PMID- 8990607
TI  - Cost of administering controlled drugs in a hospice ward.
AB  - A study was undertaken in 1995 to examine the time taken to administer Controlled
      Drugs (CDs) in one of the two seven-bedded wards in the Prince and Princess of
      Wales Hospice (PPWH) in the course of one week. A stop watch was used to measure
      the time taken from the decision to give a CD until its administration was
      entered into the CD Register. The drugs used were oral morphine, oral sustained
      release morphine and diamorphine for subcutaneous administration by syringe
      driver. The grade of nurses involved in administering the CDs was also recorded.
      The time taken by D, E, F, and G grade nurses was extrapolated to the number of
      hours per annum spent administering the CDs. The hourly rate for the various
      grades was documented and the total cost calculated. The total annual cost of
      administering CDs to the seven patients in the study was calculated to be
      10,883.94 pounds. The total cost for the two wards was extrapolated to 21,767.88
      pounds. The annual cost of the CDs was 7,294.63 pounds. The total cost of the CDs
      and their administration was 29,062.51 pounds: 75% of the expenditure is the cost
      of administration. Syringe drivers cost twice as much to administer as sustained
      release morphine tablets.

PMID- 8990608
TI  - Does where you live predict health related behaviours?: a case study in Glasgow.
AB  - In a study of four socially contrasting neighbourhoods in Glasgow, three health
      related behaviours (diet, smoking and participation in sport) were independently
      associated with neighbourhood of residence among adults after controlling for
      gender, age, social class and income. Policies aiming to improve the health of
      the population should take into account local neighbourhoods as well as
      individuals living within them.

PMID- 8990609
TI  - The 'Clinical Audit Enabler--a clinical audit resource reference guide'.

PMID- 8990610
TI  - Unplanned readmissions of elderly patients.
AB  - OBJECTIVE: This study was undertaken to determine the prevalence of unplanned
      readmissions in Geriatric Medicine in Aberdeen and to examine their nature in
      order to establish how many of them were avoidable. DESIGN: Patients living
      within Aberdeen who were discharged from Care of the Elderly Assessment Wards in
      one hospital between 1 August 1994 and 31 January 1995 were identified. Any
      subsequent unplanned readmissions of this population to any local hospital within
      28 days were identified and formed the study's sample. Subsequent comparison with
      the non-readmitted population yielded readmission rates. The nature of each
      episode was investigated by obtaining a wide range of data (e.g. from medical and
      nursing notes) soon after readmission and by the audit team subsequently
      identifying principal and associated causative factors. A questionnaire was also
      sent to the discharging consultant and the patient's GP seeking opinions on
      whether readmission was avoidable and these were weighted equally with the audit
      team's opinion in order to establish avoidability. SETTING: The patients were all
      discharged from the nine Care of the Elderly Assessment wards at Woodend Hospital
      in Aberdeen and readmitted to any NHS hospital within Aberdeen. SUBJECTS: The
      subjects were patients living within Aberdeen who satisfied the above criteria.
      RESULTS: There were 109 episodes of readmission resulting from 713 discharges,
      making a readmission rate of 15.3%. The readmitted population was elderly with
      multiple medical problems; 50% lived alone. In 87% of cases the principal
      causative factor in readmission was medical, most commonly involving relapse of
      illness. The remaining 13% were 'social' in nature. Response rates to the
      questionnaire by GP's and Consultants were excellent (96% and 99% respectively)
      and 34 cases emerged where either party, or both, thought readmission to be
      avoidable. These cases were subject to further review by the audit team and in
      this way 16 of the 34 cases were judged to be avoidable. The main area for
      improvement was considered to be pre-discharge assessment of home circumstances.
      CONCLUSION: The majority of unplanned readmissions were medical in nature and
      unavoidable. The use of rates of unplanned readmission as a measure of clinical
      outcome in care of the elderly is unsatisfactory as they do not accurately
      reflect the quality of in-patient care.

PMID- 8990611
TI  - Suicide by young men in Lothian 1993 and 1994.
AB  - OBJECTIVES: To examine the circumstances surrounding the suicides during 1993 and
      1994 of young men aged 20-29 from the Lothian region. METHODS AND MATERIALS: The
      list of suicides for Lothian residents in this group was obtained from the
      General Registry Office and information relating to these people abstracted from
      records held in General Practice and at the Forensic Medicine Unit at the
      University of Edinburgh. RESULTS: Thirty-nine men met the selection criteria
      which gave a suicide rate of 28.7/100,000. Twenty-five had zero blood alcohol
      recorded post mortem and ten had blood alcohol concentrations above the legal
      driving limit of 80 mg/100 ml. Ten (26%) had seen their General Practitioner (GP)
      in the week and 13 (33%) in the month before suicide. Previous suicide attempts
      (seven within a year of death) were recorded in 19 men. Ten men left suicide
      notes. CONCLUSION: Using an overall rate to describe suicide hides the complexity
      of the issues involved: the inclusion or not of undetermined deaths in numerical
      targets also causes confusion. Targets should be interpreted carefully and
      suicide rates should not be considered as a proxy for the mental health status of
      a population. Prevention cannot be the domain of only the GP. Assessment of
      suicide risk should be integrated as part of improved mental health training for
      all health service staff.

PMID- 8990612
TI  - Factors associated with admission to hospital following emergency psychiatric
      assessment.
AB  - Psychiatric emergencies account for a large proportion of total referrals and
      admissions yet there has been little research in the United Kingdom into factors
      associated with admission after emergency psychiatric assessment. We conducted a
      one year prospective study of all emergency referrals from Borders Region in
      Scotland. Four hundred and eighty-seven emergencies were assessed and 153 (31%)
      of these were admitted. The main predictors of admission after stepwise logistic
      regression analysis were: risk to self (odds ratio 1.76 for each point increment
      on a five point scale, 95% confidence intervals 1.43 to 2.15), current contact
      with the psychiatric services (2.46; 1.52, 3.98) and psychotic diagnosis (2.38;
      1.47, 3.87). Compared to subjects assessed at home, those assessed at the
      psychiatric hospital were more likely to be admitted (3.73; 1.99, 6.99) and self
      referrals were less likely to be admitted than General Practitioner referrals
      (0.22; 0.08, 0.55). Our results suggest that future studies of emergency services
      should investigate and control for both clinical and service variables.

PMID- 8990613
TI  - The need for renal replacement therapy in Scotland.
AB  - Each year 80-100 people per million of the population develop end stage renal
      failure and are medically suitable for renal replacement therapy. This need has
      been met in Scotland in each of the last three years. With current knowledge
      there is no prospect of measures to prevent renal disease affecting this number
      in the foreseeable future. The number of patients on renal replacement therapy in
      Scotland will increase over the next 15 years to approximately 160% of the
      current number. The mean age of patient on replacement therapy will increase
      progressively over the next 15 years. The increase in numbers will be in patients
      receiving 'in centre' haemodialysis and in those with functioning renal
      transplants. To meet this increase an approximately 3-4 increase in the current
      'in centre' haemodialysis facilities will be required. Additional haemodialysis
      centres should be established to reduce the time spent by patients travelling for
      treatment and to avoid centres becoming 'impersonal' by becoming too large. Moves
      to increase the transplantation rate should be encouraged as transplantation
      offers the best quality of life for patients. Research should be directed towards
      improving long term graft survival.

PMID- 8990614
TI  - Social circumstances reports--a critical evaluation.
AB  - A retrospective analysis was taken of the content of 50 Social Circumstances
      Reports. On average only 25% of the information contained within reports
      described current social circumstances, the rest being devoted to information
      largely contained within the patient's psychiatric case notes and to the Mental
      Health Officer's own opinions on management. The structure of the reports
      mirrored the requirements of the Mental Welfare Commission rather than the needs
      of the Responsible Medical officer, indicating a need for further clarification
      of the role of the Mental Health Officer in the management of detained patients.

PMID- 8990615
TI  - An audit of BCG immunisation and tuberculin skin testing in Scotland. Scottish
      BCG Study Group.
AB  - BACKGROUND: BCG vaccination of all tuberculin-negative schoolchildren has been
      undertaken in the United Kingdom since 1954. In light of the ten-fold decline in
      tuberculosis, mass vaccination may no longer be justified. Since most
      tuberculosis cases now occur among identifiable high-risk groups, restriction of
      vaccination to these groups may be more appropriate. Before such changes can be
      recommended, further information is required on current practice within Scotland.
      OBJECTIVE: To determine current BCG vaccination practice within Scotland, in
      order to inform planning of future immunisation services. DESIGN: Postal
      questionnaire survey. SETTING AND SUBJECTS: The questionnaires were posted to the
      Consultant in Public Health Medicine responsible for Communicable Disease Control
      in each of the fifteen Scottish Health Boards. RESULTS: Completed questionnaires
      were returned by all 15 Health Boards. Marked variations were reported in the
      vaccination of both schoolchildren and high-risk groups. Six (40%) Health Boards
      immunised all tuberculin-negative children, whereas the remainder excluded those
      with evidence of previous BCG vaccination. All Health Boards immunised contacts
      of tuberculosis cases, 11 offered it to healthcare workers and 11 to immigrants
      from countries with a high prevalence of tuberculosis. However, only 7 offered it
      to the offspring of high-risk ethnic groups, 5 to students and 4 to animal
      workers. CONCLUSION: There are marked variations in current BCG vaccination
      practice. Greater efforts are required to ensure that high-risk groups receive
      vaccination.

PMID- 8990616
TI  - Auditing out-of-hours primary medical care.
AB  - As a preliminary to evaluating the introduction of a primary care emergency
      centre in Midlothian, information was recorded about 2,236 out-of-hours contacts
      made with eight general practices in the ten weeks before the centre opened. The
      overall rate of calls was estimated at 265 cells per 1,000 patients per year,
      with 63% of calls resulting in a home visit, 8% in the patient being seen at the
      surgery and 29% in telephone advice only; 18% of the out-of-hours calls generated
      a night visit fee. Eighty-five per cent of patients who requested a home visit
      were seen by a doctor and 15% of patients contacting their general practitioner
      out of hours were referred to hospital, either for admission or for treatment in
      an accident and emergency department. Doctors classified 61% of the calls as
      necessary, 29% as unnecessary and were unsure about the need for 9% of calls.

PMID- 8990617
TI  - Audit on the use of prophylactic parenteral antimicrobial agents and the use of
      co-amoxiclav and metronidazole.
AB  - Following the recommendations of a previous audit, specific objectives were
      chosen for reaudit. The aim was to measure the adherence to agreed protocols for
      the use of prophylactic antimicrobial agents; including the use of the once only
      part of the Kardex and to measure the adherence to protocols for the use of
      parenteral co-amoxiclav and metronidazole. The audit was conducted in the same
      hospital as the original study. Data was collected for one month on all patients
      receiving prophylactic antimicrobial agents, parenteral co-amoxiclav or
      metronidazole. A microbiologist assessed the compliance to the agreed written
      protocols, which had been distributed and explained to each resident. One hundred
      and eighty-eight patients received 226 antimicrobial courses (649 doses). Seventy
      two per cent of courses were considered appropriate compared with 65% in 1993.
      The criteria for this audit only allowed one cephalosporin choice per directorate
      and accounted for the inappropriateness of choice to be 19% compared with 12% in
      1993. This was confined to one directorate and an overall improvement of 79%
      would have been achieved if any cephalosporin could be chosen as 1993. Eighty-two
      per cent of doses were considered appropriate if written in the once only part of
      the Kardex or the anaesthetic sheet compared with 51% of those written in the
      general part. Only nine per cent of courses were too long compared with 16% in
      1993. Fifty seven patients were given 125 days of co-amoxiclav, 94 days for
      treatment and 31 days for prophylaxis. Co-amoxiclav use overall was 33% less than
      1993 with an improvement of appropriateness from 30% to 68%. CONCLUSIONS: An
      overall improvement in the appropriateness of prophylactic antibiotic use was
      achieved by the implementation of agreed protocols. An automatic stopping system
      reduced the continuation of prophylaxis.

PMID- 8990618
TI  - Medical and dental staffing in the national health service in Scotland in 1995.

PMID- 8990619
TI  - Minimal access therapy: scope, evaluation and future direction.

PMID- 8990620
TI  - In vitro development of hematopoietic system from mouse embryonic stem cells: a
      new approach for embryonic hematopoiesis.
AB  - We developed an efficient differentiation induction system (OP9 system) from
      mouse embryonic stem (ES) cell to blood cells by coculture on a novel stromal
      cell line, OP9. This stromal cell line does not produce functional macrophage
      colony-stimulating factor (M-CSF) and presumably the deficiency of M-CSF
      production of OP9 cells might induce preferential differentiation of ES cells
      into hematopoietic cells other than the monocyte-macrophage lineage. ES cells
      gave rise to embryonic primitive erythrocytes, and then adult type definitive
      erythrocytes, myeloid and B lineage cells. The OP9 system should facilitate to
      elucidate the molecular mechanisms of hematopoietic system development and
      hematopoietic cell differentiation.

PMID- 8990621
TI  - Pyothorax-associated lymphoma.
AB  - In 1987, we reported three patients with pleural lymphoma developed after a 22-30
      year history of pyothorax resulting from artificial pneumothorax for the
      treatment of pulmonary tuberculosis or tuberculous pleuritis. Based on the
      pathologic and epidemiologic studies, we regarded the chronic pyothorax (CP) to
      be etiologically important in the development of pleural lymphoma. Through a
      nation-wide study in Japan, 37 cases of pleural lymphoma were collected. Pleural
      lymphoma had developed during the 20 year history of CP in all patients.
      Histologically all were non-Hodgkin's lymphoma with the diffuse large cell type
      being the most common. Immunologic and immunohistochemical studies revealed that
      32 out of 33 cases were of B-cell lymphoma. From these findings, we proposed the
      term pyothorax-associated lymphoma (PAL). We examined the presence of Epstein
      Barr virus (EBV) genome on the paraffin-embedded specimens in 34 PAL cases and 16
      cases of CP alone. Combined polymerase chain reaction (PCR), in situ
      hybridization, and immunohistochemistry revealed that the EBV genome was detected
      in lymphoma cells in all PAL, but only one of the cases with CP alone. These
      findings suggested the etiological role of EBV for the development of PAL. We
      also described here the character of cell lines established from PAL, association
      of PAL with Kaposi's sarcoma-associated herpes virus, results of a case-control
      study on risk factors for development of PAL, and p53 mutations.

PMID- 8990622
TI  - Cytokine therapy for hematological malignancies.
AB  - Recently various cytokines have been introduced into the clinic and have played
      important therapeutic roles in the treatment of hematological malignancies. Among
      these cytokines, I have focused on interferon (IFN) and granulocyte (G) or
      granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently
      the most useful cytokines, in this review. IFN-alpha has been approved for
      chronic myelogenous leukemia (CML), multiple myeloma and hairy cell leukemia. In
      addition, IFN-alpha has therapeutic potentials for low grade non-Hodgkin's
      lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma. Thus, IFN
      alpha is one of the most useful and wide-ranging antitumor agents in
      hematological malignancies. Most striking effects have been studied in chronic
      phase CML. Cytogenetic responses are seen in 30-40% of the treated patients and a
      complete cytogenetic response can be seen in about 10%. Long-term survival can be
      expected in these patients. Considering the risk of graft-versus-host disease
      associated mortality in allogeneic bone marrow transplantation, the category of
      treatment is difficult to choose in IFN-responsive patients. Elucidation of the
      antitumor mechanism of IFN, as a prototype for other biological response
      modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced
      the duration of neutropenia, incidence of infectious episodes and days of
      hospitalization following cancer chemotherapy or stem cell transplantation. CSFs
      have also been used to mobilize peripheral blood stem cells and to increase dose
      intensity of chemotherapeutic agents. Leukemic cells from many patients with
      acute myelogenous leukemia (AML) have surface receptors for CSFs and may
      proliferate in response to CSFs. However, several randomized studies showed that
      CSFs can be used safely and effectively in augmenting neutrophil recovery in
      patients with AML when given after induction chemotherapy. Various trials have
      been made to prime leukemic cells by CSFs to make them more susceptible to
      chemotherapy, but no convincing evidence has been obtained.

PMID- 8990623
TI  - Herbimycin A down-regulates messages of cyclin D1 and c-myc during erythroid
      differentiation of K562 cells.
AB  - The ansamycin antibiotic, herbimycin A, is a potent tyrosine kinase inhibitor,
      and induces the erythroid differentiation of bcr-abl-possessing K562 cells. The
      growth of K562 cells was cytostatically reduced to less than 50% of the control
      level at 48 h by 0.5 microgram/ml of herbimycin A treatment. A total of 12% and
      53% of the treated cells were benzidine-positive at 24 h and 48 h, respectively.
      The percentage of cells in the S phase decreased rapidly from 60% to 15% after 12
      h of treatment. The reduction of S phase cells persisted until 24 h, whereas the
      G1 population conversely increased. Then underphosphorylated retinoblastoma gene
      product increased from 6 h to 24 h, but returned to baseline at 48 h. Most cell
      cycle controlling genes were unchanged by herbimycin A treatment. However, both
      cyclin D1 and c-myc were prominently down-regulated in the early phase of
      treatment, corresponding to the decline of the S phase population. Cyclin D1 was
      initially down-regulated to an undetectable level at 6 h, although its expression
      recovered gradually from 12 h and returned to baseline at 24 h. c-myc was also
      down-regulated from 1 h to 6 h. These data suggest that signals originating from
      bcr-abl kinase are at least partly transduced through both c-myc and cyclin D1,
      and that herbimycin A-induced erythroid differentiation occurs during or after
      the cessation of growth due to interference with these signals.

PMID- 8990624
TI  - p53-independent induction of p21 (WAF1/CIP1) during differentiation of HL-60
      cells by tumor necrosis factor alpha.
AB  - We demonstrated that tumor necrosis factor-alpha (TNF-alpha) rapidly and markedly
      enhances p21 gene and protein expression prior to monocytic differentiation and
      apoptosis in p53-null HL-60 cells. TNF-alpha induced early small and delayed
      large peaks of apoptosis at 6 and 48 h of incubation, respectively. At 24 h of
      incubation, apparent monocytic differentiation of the cells was noted. Down
      regulation of c-myc and c-myb and G0/G1 arrest were observed at 6-12 and 36 h,
      respectively. Actinomycin D markedly inhibited TNF-alpha-induced p21 mRNA
      expression, suggesting that the p21 gene is induced at the transcriptional level.
      We confirmed that TNF-alpha induces p53-independent apoptosis in HL-60 cells,
      which accompanies monocytic differentiation.

PMID- 8990625
TI  - Regulation of neutrophil O2- production by neutrophil-endothelial cell
      interaction via CD11b: its modulation by tumor necrosis factor-alpha (TNF-alpha)
      and lipopolysaccharide (LPS).
AB  - Polymorphonuclear leukocyte-endothelial cell (PMN-EC) adhesion and the O2-
      production by subsequently triggered polymorphonuclear leukocytes (PMN) must be
      involved in the development of multiple organ failure at septic inflammatory
      sites. In this study, the adhesion and O2- production of PMN treated with LPS and
      serum, were markedly enhanced on the EC monolayer by treatment with TNF-alpha or
      LPS. However, in the intact EC monolayer, neither adhesion nor O2- production was
      increased. Monoclonal antibodies (mAb) against CD18, CD11b, and ICAM-1 inhibited
      PMN-EC adhesion. All antibodies except for anti-CD11b mAb had no effect on O2-
      production by adhered PMN. Anti-CD11b mAb stimulated O2- production in a PMN cell
      suspension. The pertussis toxin, an inhibitor of some G-proteins, inhibited this
      reaction. These findings indicate that the adhesion mediated by CD11b provides
      the signal for O2- production by PMN. This O2- production may involve a signal
      transduction mechanism mediated by pertussis toxin-sensitive G-proteins.

PMID- 8990626
TI  - Circulating endogenous thrombopoietin, interleukin-3, interleukin-6 and
      interleukin-11 levels in patients undergoing allogeneic bone marrow
      transplantation.
AB  - To elucidate the physiologic role of thrombopoietin (TPO) for hematologic
      reconstitution following allogeneic bone marrow transplantation (BMT), serum TPO
      levels as well as interleukin-3 (IL-3), IL-6 and IL-11 were serially measured in
      55 samples from 3 patients who underwent allogeneic BMT using an enzyme-linked
      immunosorbent assay (ELISA). The TPO level was higher in the serum taken during
      marrow aplasia than in the pretransplant serum. The serum TPO levels and platelet
      counts showed a strong inverse relationship in all patients examined. We also
      sequentially measured endogenous serum TPO levels before and within 36 h after
      platelet transfusions. Endogenous serum TPO levels were inversely correlated with
      platelet mass following platelet transfusions. Serum levels of IL-3 had no
      apparent correlation with platelet counts and serum levels of IL-11 remained
      below the detection levels (31.3 pg/ml) in all samples. Serum levels of IL-6 were
      high during myeloaplasia and more upregulated in the febrile period. These
      findings support the view that TPO is the central regulator for megakaryopoiesis
      in vivo and the rationale for its clinical use after allogeneic BMT.

PMID- 8990627
TI  - Low prevalence of activated protein C resistance and coagulation factor V Arg506
      to Gln mutation among Japanese patients with various forms of thrombosis, and
      normal individuals.
AB  - Resistance to activated protein C (APC), recently reported to be the most
      prevalent inherited cause of thrombosis among Caucasians, is associated with a
      single point mutation in the coagulation factor V gene. We investigated the
      prevalence of APC resistance and the factor V gene mutation (R506Q) in 34
      consecutive Japanese patients with venous thrombosis or pulmonary thromboembolism
      and 63 control subjects. Three of the 33 patients examined (9%) had an APC ratio
      below the 5th percentile of control values (2.27), but all were above 2.0. The
      factor V mutation (R506Q) was not detected in the 29 patients studied, including
      the 3 patients whose APC ratios were below 2.27, or in 53 controls. In a tissue
      factor-based factor V assay to detect APC resistance recently described by Le et
      al. (Blood 1995;85:1704-1711), all patients studied were found to be normal
      including the three with a low APC ratio. We conclude that APC resistance and
      factor V gene mutation are less prevalent in Japan than in several European
      countries.

PMID- 8990628
TI  - Gastrointestinal angiodysplasia in congenital platelet dysfunction.
AB  - We herein report three cases of repeated massive bleeding from the stomach and
      small bowel. One patient suffered from both thrombasthenia (type II) and von
      Willebrand disease (type 1) simultaneously. Two others had Bernard-Soulier's
      syndrome (BSS). One patient with BSS had bleeding from gastric angiodysplasia and
      was treated endoscopically by clipping. The other patients had massive bleeding
      from the small intestine, and had partial resection of the affected small
      intestine. Histologically, irregular dilatation and proliferation of the blood
      vessels were demonstrated in the submucosa in bleeding spots from a resected
      small intestine, and these findings were consistent with the features of acquired
      angiodysplasia. The development of gastrointestinal angiodysplasia may not only
      be associated with a dysfunction of von Willebrand factor but also with that of
      platelets.

PMID- 8990629
TI  - Sideroblastic anemia recurring during two pregnancies.
AB  - A 25-year-old lady presented with a severe normocytic anemia (Hb 5.3 g/dl) and a
      sideroblastic marrow at the end of her first pregnancy. Six months into the
      puerperium, after the transfusion of a total of 8 units of red cells, there was
      apparent spontaneous improvement and then she was lost to follow-up. After a
      second pregnancy without clinical problems, she presented during a third
      pregnancy, at the age of 30 years, with similar hematological findings. Twenty
      two months later she was well with a normal blood count. One possible reason for
      relapse in pregnancy is the increased demand for pyridoxine that occurs, but only
      one other case of sideroblastic anemia relapsing during pregnancies has been
      reported.

PMID- 8990631
TI  - Again and again.

PMID- 8990630
TI  - Androgen therapy in combination with granulocyte colony-stimulating factor and
      erythropoietin in a patient with refractory anemia.
AB  - Initial treatment with androgen (metenolone acetate) alone for 19 weeks had no
      effect in a 45-year-old Japanese female with refractory anemia (RA). The patient
      achieved trilineage hematologic recovery after addition of recombinant human
      granulocyte colony-stimulating factor (G-CSF) and recombinant human
      erythropoietin (Epo) to the androgen therapy. Anemia progressed after the
      cessation of metanolone acetate, but was effectively treated by the
      readministration of metenolone acetate. Thus, the androgen therapy in combination
      with hematopoietic growth factors such as G-CSF and/or Epo may be effective in
      patients with RA.

PMID- 8990632
TI  - Maxillary augmentation with a microvascularly anastomosed fibula: a preliminary
      report.
AB  - The high resorption rate of nonvascularized bone grafts can be appreciably slowed
      with the use of endosseous implants and implant-supported prostheses. In cases of
      extreme atrophy, graft fixation with implants is hardly possible. Especially in
      the presence of compromised overlying soft tissues, the consolidation of such a
      graft can also present problems. Improved results can be obtained through use of
      revascularized bone grafts. Such a method using an anastomosed fibula graft to
      augment the maxilla is illustrated by a clinical case. After harvesting the
      graft, the side to come into contact with the alveolar crest is denuded of
      periosteum, and cuneiform ostectomies are made into the graft to facilitate its
      adaptation to the maxillary arch. The graft is anastomosed to the facial vessels
      through an intraoral route and can be placed in such a way as to simultaneously
      correct any existing crossbite. In contrast to an iliac graft, the implants can
      be placed bicortically in a fibular graft.

PMID- 8990633
TI  - A dynamic modal testing technique for noninvasive assessment of bone-dental
      implant interfaces.
AB  - A dynamic modal testing technique has been developed to noninvasively assess the
      interface surrounding an endosseous dental implant with a lateral tap from an
      impedance head hammer. The technique assesses the rotational stiffness of the
      interface based on the shape of the power spectrum of the force-time curve
      produced on impact. In vitro experiments were performed to determine the
      sensitivity of the technique for detecting clinically relevant structural
      differences between interfaces. The modal test data were able to distinguish
      interfaces based on the type of bone at the interface and the degree of fixation
      between the implant and the interface.

PMID- 8990634
TI  - Guided bone regeneration using resorbable and nonresorbable membranes: a
      comparative histologic study in humans.
AB  - Resorbable membranes of poly(lactic acid) and poly(glycolic acid) (PLA/PGA) were
      compared to nonresorbable expanded polytetrafluoroethylene (e-PTFE) membranes in
      the treatment of defects around titanium dental implants placed in postextraction
      sockets. Two partially edentulous and three completely edentulous patients
      requiring implant-supported restorations participated. Sixteen Branemark implants
      were placed into extraction sockets and covered with modified titanium cover
      screws, called harvest cover screws, which allow tissue biopsy at second-stage
      implant surgery. Seven defects were treated with PLA/PGA membranes, five were
      treated with e-PTFE membranes, and four were left untreated (control sites).
      After 6 months of healing, the harvest cover screws were retrieved and processed
      for light microscopy examination together with the regenerated tissues. Very
      little or no bone formation was detected in control specimens. The e-PTFE
      membranes were found to be the most effective barrier material, in that denser
      and a greater amount of regenerated bone was found. The PLA/PGA membranes
      produced some bone regeneration when compared to control sites, but to a lesser
      extent compared to e-PTFE sites.

PMID- 8990635
TI  - A modified surgical protocol for placing implants in the maxillary tuberosity:
      clinical results at 36 months after loading with fixed partial dentures.
AB  - The purpose of this study was to investigate the impact of a modified surgical
      protocol and the survival of implants placed in the posterior maxilla. Forty-two
      implants were placed in the maxillary posterior area of 29 partially edentulous
      patients (17 men, 12 women; mean age 50 years; range 38 to 62 years) according to
      the modified surgical protocol. Twenty-nine of these implants had been placed
      into the maxillary tuberosity. All implants were checked radiologically every 12
      months with a customized film holder. The restorations were fixed partial
      prostheses. Only 1 of the 42 implants was lost at stage 2 surgery. Results
      suggest that considerable benefits may be obtained by modifying a standard
      surgical protocol to maximize the results for a particular anatomic site.

PMID- 8990636
TI  - Implants in adolescents: a literature review and case reports.
AB  - A retrospective review of a limited number of adolescents with implants was
      conducted to compare the behavior of these implants with studies in which
      implants had been placed in growing animals. Growth of the facial skeleton is
      also reviewed. Implants placed in the growing alveolus behave like ankylosed
      teeth and become submerged as the surrounding bone grows. Cessation of facial
      growth should occur prior to implant placement in adolescents.

PMID- 8990637
TI  - Smoking and implant failure--benefits of a smoking cessation protocol.
AB  - This prospective study reviews the early outcomes of 223 consecutive Branemark
      implants placed in 78 patients by one operator. Patients were divided into three
      groups: nonsmokers (NS); smokers who followed a smoking cessation protocol (SQ);
      and smokers who continued to smoke (SNQ). There was a statistically significant
      difference between failure rates in the NS and SNQ groups (P < .005) and between
      the SQ and SNQ groups (P < .05), but none between the NS and SQ groups. It is
      concluded that the smoking cessation protocol described shows considerable
      promise in improving success rates for osseointegration in smokers who follow it.

PMID- 8990638
TI  - Augmentation of the maxillary sinus floor with particulated mandible: a
      histologic and histomorphometric study.
AB  - This study presents the results of 10 consecutive patients treated with
      unilateral bone augmentation of the maxillary sinus floor using particulated
      mandible harvested from the symphysis. Endosseous titanium implants (Branemark)
      were placed 6 months after the transplant procedure. Thirty self-tapping implants
      were placed with a mean follow-up period of 26 months (range 12 to 46 months).
      Bone biopsy specimens were obtained from the donor site and the residual alveolar
      process at the time of grafting. A second biopsy specimen was obtained from the
      grafted site after 6 months of healing (at time of implant placement), and a
      third biopsy specimen was obtained after 12 months of healing (at time of
      abutment placement). Histomorphometry was performed on microradiographs using a
      computerized image analysis system. The bone volume fraction at the donor site
      before particulation was 58% +/- 19%, and the volume fraction at the residual
      alveolar process was 45% +/- 15%. The mean volume fraction of bone in the grafted
      area increased from 40% +/- 12% after 6 months of healing to 48% +/- 10% after 12
      months. Histology of the retrieved bone biopsy specimens revealed normal healing
      and bone maturation in all samples.

PMID- 8990639
TI  - The extent of maintenance required by implant-retained mandibular overdentures: a
      3-year report.
AB  - Astra Tech implants were used to support implant-retained mandibular overdentures
      for 25 edentulous patients (12 with magnet retention and 13 with stud retention).
      The patients were followed for 3 years, and a detailed record was kept of the
      extent of maintenance required after placement of the dentures. There were 64
      episodes of maintenance related to the overdentures in the magnet retention group
      and 63 episodes of maintenance in the stud retention group. Episodic maintenance
      was greatest during the first year, with the magnet group having 30 episodes and
      the stud group 34. The number of visits required for maintenance related to both
      the maxillary and mandibular dentures was 117 for the magnet retention group and
      86 for the stud retention group. There was no statistically significant
      difference in the amount of postplacement care between the two groups.

PMID- 8990640
TI  - Concept of surgical and implant-supported prostheses in the rehabilitation of
      patients with oral cancer.
AB  - Thirteen irradiated and 14 nonirradiated patients were treated after resection of
      a malignant oral lesion. With a follow-up period of 26 months, 3 of 48 implants
      in nonirradiated patients and 4 of 57 implants in irradiated patients failed. In
      comparison to implant-tissue-supported prostheses, exclusively implant-supported
      prostheses demonstrated better results with regard to soft tissue trauma and
      function of the prosthesis.

PMID- 8990641
TI  - A custom titanium implant-retained single-tooth restoration: a clinical report.
AB  - Titanium is an inexpensive metal that can be used to create custom cast
      restorations. Although special investment and casting equipment is needed to make
      titanium castings, the potential benefit of inexpensive, biocompatible, and
      custom restorations is significant. Porcelain can easily be applied to titanium
      with excellent bond strength and esthetics. Problems associated with casting
      roughness and fit can be corrected using electrical discharge machining. A method
      of diagnosis and treatment planning that evaluates the restorative space prior to
      implant placement and eliminates the use of machined components is presented.

PMID- 8990642
TI  - Three-dimensional templates for placement of root-form dental implants: a
      technical note.
AB  - This report describes a method for gathering information to assist in properly
      placing dental implants. A diagnostic template is first fabricated, incorporating
      radiographic markers. Radiographs of the template are obtained, and data from
      their study are transferred to the laboratory to facilitate the fabrication of a
      surgical template. This procedure has the potential to map implant sites three
      dimensionally. Template use can result in a greater number of implants placed in
      optimal positions.

PMID- 8990643
TI  - Detection and measurement of inflammatory cytokines in implant crevicular fluid:
      a pilot study.
AB  - Peri-implantitis has been shown to possess clinical characteristics similar to
      those of periodontitis. This pilot study was conducted to determine levels of
      inflammatory cytokines in crevicular fluid from healthy implants and those
      implants affected by peri-implantitis. Fifty implants from 13 patients were
      examined. A clinical examination was performed, and gingival crevicular fluid
      samples were collected and analyzed for cytokines. Implants were categorized
      clinically as healthy, early peri-implantitis, or advanced peri-implantitis.
      Interleukin-1 beta was detected in the crevicular fluid of implants in all three
      groups (healthy = 59.47 +/- 15.55 pg/site; early peri-implantitis = 460.77 +/-
      35.67 pg/site; and advanced peri-implantitis = 191.10 +/- 21.60 pg/site [mean +/-
      SEM]). These results indicate that interleukin-1 beta is present in implant
      gingival crevicular fluid and may be modulating attachment loss in implants
      suffering from peri-implantitis. Thus, interleukin-1 beta may be used to monitor
      disease progression.

PMID- 8990644
TI  - Electrophysiologic evidence showing the existence of sensory receptors within the
      alveolar bone in anesthetized cats.
AB  - Single-nerve activities were recorded in the gasserian ganglia of anesthetized
      cats by glass extracellular micro-electrodes to determine whether sensory endings
      exist within the alveolar bone. Trigeminal cells responded to mechanical and/or
      thermal stimulation applied to the maxillary bone. Some were activated by
      specific kinds of fairly precise mechanical stimuli (moderate forces applied in a
      preferential direction); others exhibited a coarse mechanical sensitivity. In
      addition, electrical stimulation was applied to the maxillary bone to determine
      the conduction velocities of the relevant fibers. These mainly ranged between 1
      and 6 m/s, which indicates that the fibers belonged to the small-diameter
      category (thinnest myelinated and unmyelinated fibers). Similar results were
      obtained from animals with osseointegrated implants. It was concluded that the
      alveolar bone is endowed with sensory endings capable of detecting mechanical and
      thermal changes, and that these receptors may provide compensatory sensitivity in
      edentulous subjects whose main (periodontal) sensitivity has been eliminated.

PMID- 8990645
TI  - Computer-assisted planning of oral implant surgery: a three-dimensional approach.
AB  - A planning system for oral implant surgery based on a true three-dimensional
      approach is described. This system allows the interactive placement and
      adjustment of axial-symmetric models representing implants in the jawbone
      structures visible on computerized tomographic volume data. Simultaneous
      visualization is possible on two-dimensional reformatted images and on three
      dimensional-derived bone surface representations. This approach largely
      outperforms the manual planning practice based on two-dimensional dental
      computerized tomographic images printed or on film.

PMID- 8990646
TI  - A 1-year radiographic evaluation of marginal bone around dental implants.
AB  - The aim of this study was to report alveolar bone loss during the first 12 months
      after implant abutment connection. Marginal bone loss around 62 endosseous root
      form implants in 62 patients was measured on periapical radiographs. Changes in
      bone density were measured by the digital subtraction image radiographic method.
      At 3-month intervals for 1 year, bone loss around the four types of implants used
      (standard series, mini series, and hexlock implants of the Steri-Oss system; and
      3i standard implants) was investigated. Rapid bone loss around all four implant
      types occurred in the first 3 months. Most of the implants showed resorption of
      alveolar bone beyond the polished neck at 12 months. The bone level stabilized at
      the first thread of the implants with no correlation to either the time of
      exposure of the polished neck or the type of implant. Bone density decreased at
      the marginal bone and increased at the newly formed alveolar crest.

PMID- 8990647
TI  - Blood pressure and heart rate dynamics during and after exercise in an unselected
      population.
AB  - It has been suggested that the systolic blood pressure (SBP) response to exercise
      may be useful in predicting future hypertension. However, controversy exists as
      to whether the SBP response to exercise in borderline hypertensives is actually
      greater than normotensives or merely increases equally but from a higher resting
      value. Our aim was to determine the influence of resting SBP, age and sex on
      changes of SSP during exercise for both healthy subjects and untreated mild
      hypertensives. Three hundred and eighteen (230 males) underwent a self limited
      exercise protocol. SBP was measured at baseline and between the 2nd and 3rd
      minutes of each exercise stage. Age was positively related to SBP at rest and
      during exercise. The magnitude of SBP change induced by exercise was similar
      irrespective of the level of resting SBP. The relationship between resting SBP
      and the absolute SBP change which occurred during exercise was independent of
      sex. Our findings indicate that (i) age is positively related to SBP at rest and
      during exercise, (ii) SBP rises equally during exercise irrespective of its
      resting level and (iii) males and females have a similar pattern of BP response
      to exercise.

PMID- 8990648
TI  - Audit of a rural hospital's coronary care unit: comparison of two predictive
      instruments of acute myocardial infarction mortality.
AB  - The purpose of the study was to compare observed mortality of a rural hospital
      coronary care unit with mortality rates estimated by two predictive instruments
      of mortality. The mortality rates of 86 consecutive patients with confirmed acute
      myocardial infarction were compared with those predicted by the presence or
      absence of eight risk factors for mortality identified by the Thrombolysis in
      Myocardial Infarction (TIMI) trial, and mortality predicted by a logistic
      regression equation LRE). Seventeen patients (20 per cent) died within 6 weeks of
      admission; the number of TIMI risk factors present predicted a mortality of 9.8
      per cent, and the instrument of Selker's predicted a mortality of 25.9 per cent.
      Patients with 3 TIMI risk factors had a significantly higher mortality than
      predicted (46.2 versus 13.0 per cent, p < 0.01). There were no significant
      differences between the receiver operating characteristic (ROC) curve of either
      instrument. The predictions of Selker's instrument, however, showed no
      significant difference from observed mortality, even when the patients were
      grouped into quintiles, and the predicted mortality rates were corrected for any
      presumed benefit from thrombolysis. The predictive instrument of Selker more
      consistently estimates observed mortality than the presence of risk factors
      identified by the TIMI trial.

PMID- 8990649
TI  - Thoracic aortic dissection or aneurysm: clinical presentation, diagnostic imaging
      and initial management in a tertiary referral centre.
AB  - Spontaneous thoracic aortic dissection carries a high mortality despite progress
      in diagnosis and treatment. Early and accurate diagnosis is paramount and
      dependent on clinical and diagnostic imaging skills. A retrospective review of 55
      consecutive patients referred with suspected thoracic aortic dissection to a
      medical cardiology department was performed. Clinical follow up was complete to
      November 1995. Median age was 68 years (range 30-93), with 37 males, 18 females.
      Presenting complaints included interscapular chest pain in 23 (42 per cent),
      neurological deficit in 2 (4 per cent), and limb ischaemia in 8 (15 per cent). On
      examination 34 (62 per cent) patients had hypertension, 5 (9 per cent) a pulse
      deficit and 10 (18 per cent) aortic incompetence. Electrocardiography confirmed
      myocardial infarction in 1. Chest X-ray showed a widened mediastinum in 37 (67
      per cent) patients. Dissection was confirmed in 35 (64 per cent) patients (13
      DeBakey Type I, 6-Type II, 14-Type III); 10 had nondissecting aneurysm. Contrast
      aortography was equally sensitive (84 per cent) and more specific (100 per cent
      vs 80 per cent) than computed tomography for detection of dissection. Surgical
      repair was performed on 24 patients with concomitant coronary artery bypass
      grafting in 6. At follow up 33 patients were alive. Clinical diagnosis of
      thoracic aortic dissection or aneurysm may be difficult. Frequently more than one
      imaging modality may be required in order to provide all of the necessary
      information for optimal patient management.

PMID- 8990650
TI  - Breech presentation. Fetal loss associated with intended vaginal delivery.

PMID- 8990651
TI  - HELLP syndrome: a condition of varied presentation.
AB  - Three cases of HELLP syndrome are presented which illustrate its varied clinical
      presentation, the difficulty in making a diagnosis and the management problems.
      The cases varied in severity; all showed thrombocytopenia and abnormal liver
      function tests, but in one case the blood pressure remained within "normal
      limits" whereas another patient suffered grand mal seizures due to hypertensive
      encephalopathy.

PMID- 8990652
TI  - Transabdominal ultrasound and its correlation with clinical findings in
      gynaecology.
AB  - Details of 86 patients with a pelvic mass who underwent a laparotomy under the
      gynaecological service in St. Vincent's Hospital were reviewed. Findings at
      laparotomy were correlated with ultrasound findings. Overall, ultrasound appears
      to be more sensitive and specific in the determination of the origins of a pelvic
      mass compared to clinical examination. The sensitivity and specificity of
      ultrasound in detecting a uterine mass is 94 per cent and 99 per cent
      respectively. This contrasts sharply with clinical examination (sensitivity = 74
      per cent; specificity = 94 per cent). The sensitivity and specificity of
      ultrasound in detecting an ovarian mass is 92 per cent and 71 per cent.
      Ultrasound is capable of predicting benign disease with reasonable confidence but
      the prediction of malignancy is less reliable.

PMID- 8990653
TI  - Acute renal failure in orthotopic liver transplantation.
AB  - Acute renal failure (ARF) is a frequent complication of orthotopic liver
      transplantation (OLT) and is a major cause of mortality and morbidity. We report
      the incidence, management and outcome of ARF in OLT patients during the first
      year of a liver transplant programme.

PMID- 8990654
TI  - Pneumatic retinopexy versus scleral buckling: a randomised controlled trial.
AB  - Pneumatic retinopexy (PR) is a technique for repairing certain retinal
      detachments which is easier to perform than conventional sceral buckling (SB)
      surgery but has comparable results. We performed a prospective, randomised,
      controlled trial to determine for ourselves whether PR is a safe and acceptable
      procedure. Twenty patients presenting consecutively with retinal detachments
      which fulfilled the selection criteria were randomised to have their detachments
      repaired by either PR or SB, ten patients in each group. The suitable patients
      had a single retinal break or small group of breaks of not greater than one clock
      hour in size, situated within the superior eight clock hours of retina. Patients
      with significant proliferative vitreoretinopathy or other fundus disorders were
      excluded. All patients in the PR group had local anaesthesia while all those in
      the SB group had general anaesthesia. Successful reattachment of the retina was
      achieved with one or more procedures in 90 percent of the PR group and in 100
      percent of the SB group. We feel that narrowing the selection criteria for PR may
      further improve the success rate.

PMID- 8990655
TI  - Surgery for locally aggressive bone tumours.
AB  - Treatment of 16 patients with aggressive benign bone tumours and one patient with
      a low grade malignancy with a combined regimen of cryosurgery, phenolization and
      acrylic cementation is reported. Patients were aged between 9 and 51 years and
      were treated by this method between the years 1986 and 1993. Minimal follow up
      was 13 months. The commonest histological diagnosis was giant cell tumour (7),
      followed by aneurysmal bone cyst (6), chondromyxoidfibroma (3) and low grade
      chondrosarcoma (1). Patients were assessed for functional outcome and local
      recurrence. On average 86 per cent of premorbid function was restored at follow
      up and there was one local recurrence (6.29 per cent). We conclude that this is a
      satisfactory method of gaining local control of these tumours.

PMID- 8990656
TI  - Unreamed nailing of tibial fractures--a prospective study of the routine use of
      the unreamed tibial nail.
AB  - We prospectively studied 44 patients treated with the AO Unreamed Tibial Nail
      (UTN) at two orthopaedic trauma units. There were 15 open fractures: eight type
      I, four type II, one type IIIA, and two IIIB (Gustilo). The mean follow-up time
      was 13 months (range 6-24 months). There were 14 type A, 26 type B and four type
      C fractures (AO classification, Muller). All patients with the open fractures had
      surgery within eight hours of injury. Closed fractures were treated on the next
      available trauma list. The mean time to fracture union was 15.3 weeks (range 10
      26). In the closed fracture group (n = 29), the mean time to union was 14.9 weeks
      compared to 18.6 weeks for the open fracture group. There were no non-unions and
      no infections. One patient had a malunion and breakage of locking bolts occurred
      in two cases. Our results indicate that the UTN provides excellent results in the
      treatment of both closed and open fractures of the tibial shaft, with union times
      comparable to reamed techniques.

PMID- 8990657
TI  - Patient attitudes to perioperative suppository administration for postoperative
      analgesia.
AB  - Four hundred surgical patients were questioned preoperatively to ascertain their
      attitudes to suppository analgesia. Given a choice, 82 per cent of patients
      expressed a preference for intramuscular administration of diclofenac, with 18
      per cent choosing a suppository. Males were more likely than females to choose an
      intramuscular injection. Males choosing a suppository were more likely to belong
      to a higher socio-economic group while females choosing a suppository were more
      likely to be married. Twenty-three per cent of patients who initially opted for
      intramuscular administration changed to suppository administration when the
      possibility of pain or discomfort at the injection site was explained. Females
      who changed to suppository administration were more likely to belong to a higher
      socio-economic group and to be married. Twenty-seven per cent of patients
      choosing an intramuscular injection expressed concern if a suppository were to be
      inserted without consent. Eleven per cent of patients choosing a suppository
      expressed similar concern. There is an overall reluctance, particularly within
      the male population to accept suppository analgesia. Patients from higher socio
      economic groups may be more willing to accept what they perceive to be less
      traditional forms of treatment.

PMID- 8990658
TI  - The integration of evidence based medicine and personal care in family practice.
AB  - Evidence based medicine is seductive in its simplicity and few would argue with
      the philosophical concept. The reality of its application in primary care is
      rather different. It is difficult to find evidence supporting many clinical
      management decisions, it may be difficult to interpret evidence when it is
      available, and it may be difficult to apply this evidence in the consultation.
      Clinical decisions may be influenced at many levels through health policy, audit,
      protocols, and guidelines, but the individual doctor patient relationship remains
      at the core of general practice. Developing a culture of evidence based medicine
      in general practice must integrate quantitative and qualitative research,
      epidemiology and psychology and the skills of public health and family medicine.

PMID- 8990659
TI  - A laboratory review of meningococcal infections in the west of Ireland.
AB  - A review of isolates of Neisseria meningitidis and other laboratory evidence of
      meningococcal infection was carried out for the period 1990-1995. Thirty-three
      patients with evidence of meningococcal disease were identified over the six year
      period. Group B organisms were the most commonly identified, but an increase in
      Group C has occurred and is almost equal in number. Data from clinical,
      laboratory and public health sources should be centralized in a National
      Surveillance Centre.

PMID- 8990660
TI  - Deliberate ingestion of foreign bodies by institutionalised psychiatric hospital
      patients and prison inmates.
AB  - Deliberate and recurrent foreign body ingestion is a common problem among
      institutionalised patients. We review our experience with 36 cases of deliberate
      foreign body ingestion by prisoners or psychiatric patients, thirty of whom were
      institutionalised at the time of ingestion. Symptoms were frequently severe in
      the prison inmate group but, in contrast, psychiatric patients presented with
      few, if any, symptoms. A majority of objects pass spontaneously or remain in situ
      without complication. Twenty-four patients were discharged following initial
      evaluation and without specific treatment. Eight of these were reviewed
      electively and discharged within one week. Twelve patients were admitted for
      observation, seven of whom were discharged within 48 hrs. Upper gastrointestinal
      endoscopy was performed in four patients and an intragastric foreign body
      identified in two cases. Laparotomy was performed in two cases for unresolving
      mechanical intestinal obstruction. Management should be conservative when
      possible, with surgery indicated only for complications.

PMID- 8990661
TI  - Case report: combined hand access with laparoscopic pneumoperitoneum in
      intraperitoneal adhesiolysis.
AB  - Previous abdominal surgery is one of the relative contraindications to safe
      induction of pneumoperitoneum with a Veress needle. Similarly visual inspection
      with a telescope may be limited and instrumental manipulation difficult. The
      manual ability to distract bowel loops and finger dissect greatly facilitates
      adhesiolysis and this is lost with conventional laparoscopy. A novel hand-access
      port is described which combines manual tactile ability with minimally invasive
      laparoscopic adhesiolysis.

PMID- 8990662
TI  - Case report: mesenteric lymphangiomatous cyst.
AB  - Mesenteric lymphangiomas are rare benign tumours of lymphatic vessels. We present
      the case of a mesenteric lymphangioma in a 14 year old boy.

PMID- 8990663
TI  - The effects of therapy with rifampicin and isoniazid on basic investigations for
      Cushing's syndrome.
AB  - Rifampicin(R) is a potent enzyme inducer which is now widely used to treat many
      conditions. We have investigated its effect on adrenal function tests in 18
      adults with tuberculosis on rifampicin (R) and isoniazid (INH) as in-patients.
      Midnight cortisol was above 250 nmol/l in 11 patients with a mean +/- (SD) of 340
      +/- 193 nmol/l. The morning serum cortisol following 1 and 4 mg dexamethasone
      overnight was abnormal in 88.9 per cent and 83.3 per cent respectively. The
      respective mean values +/- (SD) were 350 +/- 179 and 336 +/- 279 nmol/l. The mean
      24-hour urinary free cortisol +/- SD was 513 +/- 375 nmol and was above normal in
      6 (33.3 per cent) patients. These results show that midnight cortisol,
      dexamethasone suppression tests and 24-hour urinary free cortisol are misleading
      in patients with tuberculosis on (R) and should not be employed for investigating
      such patients for Cushing's syndrome.

PMID- 8990664
TI  - Laryngeal nerve injury during thyroid surgery.

PMID- 8990665
TI  - Guidelines for the management of Helicobacter pylori-related upper
      gastrointestinal diseases. Irish Helicobacter Pylori Study Group.
AB  - The discovery of H. pylori is the most important development in gastroduodenal
      disease this century. It has completely changed our understanding of conditions
      that occur in the upper gastrointestinal tract. Eradication of the bacterium will
      cure peptic ulcer disease, decrease the symptoms of non-ulcer dyspepsia and may
      prevent gastric cancer. There has been an exponential increase in the amount of
      research in this area in recent years and, consequently, there is considerable
      confusion as to how H. pylori-related conditions should be managed. It is hoped
      that these guidelines will clarify some of these issues.

PMID- 8990668
TI  - Trends in mortality and health behaviors: status of white and African-American
      women.
AB  - A substantial proportion of mortality in the United States can be attributed to
      three major behaviors: using tobacco, maintaining an unhealthy diet, and being
      physically inactive. Using data from the South Carolina mortality files and
      Behavioral Risk Factor Surveillance System we were able to document state trends
      in mortality, cigarette smoking, physical inactivity, and unhealthy dietary
      practices. We found that, in spite of the declines in heart disease and stroke
      mortality noted nationally and in the state, the risk factor profiles for most
      women in South Carolina did not improve. This analysis further suggests that
      physical inactivity and dietary issues (excess caloric intake, low fruit and
      vegetable consumption) would be good choices for lifestyle interventions among
      women in South Carolina, not only because they ultimately affect mortality, but
      also because they exert interim effects on morbidity, including physical
      functioning and independence.

PMID- 8990669
TI  - Total shoulder arthroplasty.

PMID- 8990670
TI  - A modern tragedy: needless suffering with cancer pain.

PMID- 8990671
TI  - HIV post-exposure prophylaxis: complex issues in health care worker management.

PMID- 8990672
TI  - Sesquicentennial of the ether dome.

PMID- 8990673
TI  - Safety of dental materials.

PMID- 8990674
TI  - Managed care.

PMID- 8990675
TI  - Access to oral health services.

PMID- 8990676
TI  - Certification of competence: a national standard for dentistry in Canada.
AB  - After consulting a large community of interested parties, the National Dental
      Examining Board of Canada (NDEB) and the provincial licensing authorities
      recently made significant changes to the certification process for dentists in
      Canada. This paper provides a chronology of the evolution of national
      certification and a summary of the present certification processes for graduates
      of both accredited and non-accredited programs.

PMID- 8990677
TI  - Trends in dental education: a literature review.
AB  - The dental literature for the past 30 years, with emphasis on recent
      publications, was reviewed for articles on trends in dental education. A keyword
      search of the MEDLINE database identified 6,055 papers, from which those most
      likely to predict future trends are considered in this article. Particular
      emphasis is placed on the Institute of Medicine of the National Academy of
      Sciences 1995 study, "Dental Education at the Crossroads: Challenges and Change."
      Reactions to this U.S.-based study are also detailed. Trends in curriculum
      analysis, curriculum change and reform, curriculum length, dental school
      financing, dental student costs, dental school and university relationships,
      dental school patient care, dental research, accreditation, oral health and
      trends from outside North America are documented. In addition, a series of
      predictions are made, and a brief bibliography of the 51 most relevant references
      is included.

PMID- 8990678
TI  - A comparison of moderate and high users of Alberta's universal dental plan for
      the elderly.
AB  - The characteristics and service utilization of 2,071 high and 2,337 moderate
      users of Alberta's dental plan from 1978-79 to 1990-91 are reported. High users
      are those who used the plan for 14 consecutive years; moderate users are those
      who used the plan in seven of the 14 years. Both groups were over 74 years of age
      in 1991-92. Compared to high users, moderate users lived in less urbanized
      regions, visited denturists more often and received far more complete dentures
      and fewer partial dentures. As a percentage of their total annual plan
      expenditures, moderate users spent less on diagnostic, preventive, periodontal
      and restorative services and much more on removable prosthodontic and denturists'
      services. However, during the study period, the moderate users increased their
      annual relative expenditures for diagnostic, preventive and, especially,
      periodontal services, and decreased them for prosthodontic services. With respect
      to specific preventive and periodontal services, the percentage of total annual
      expenditures for dental prophylaxis, topical fluoride applications, periodontal
      scaling, gingival curettage, and combinations of these, was much higher for the
      high user group. Despite these differences favoring the high user group, during
      the 14 year period, the moderate user group considerably increased its relative
      expenditures for dental prophylaxis, topical fluoride and periodontal scaling
      services. While the observed differences in service expenditures between high and
      moderate users were anticipated, the shift over time to using more preventive and
      periodontal services by both groups was an encouraging harbinger of the "new
      elderly" dental patients.

PMID- 8990679
TI  - Evidence-based dentistry.

PMID- 8990680
TI  - Interpretation of bitewing radiographs. Part 1. Evaluation of the presence of
      approximal lesions.
AB  - OBJECTIVE: Bitewing radiographs are the main tool for approximal caries
      detection. However, interpretation of findings is affected by numerous factors,
      such as beam angulation, exposure conditions, morphologic variations, etc. The
      objective of the present study was to compare the ability to detect virtually
      identical, artificial lesions in different tooth surfaces. METHODS: The in vitro
      model included preparation and radiologic evaluation of approximal artificial
      lesions in premolars and molars in depths ranging from 0.00 mm to 1.50 mm.
      RESULTS: Significant differences were found in the prospect of a lesion detection
      between the different lesion depths (p < 0.0000) and between the different
      surfaces examined (p < 0.05). The interaction between lesion depth and tooth
      surface was significant at the 0.0001 level (ANOVA with repeated measures).
      CONCLUSIONS: The results indicate that initial approximal lesions of uniform size
      are more readily detected in premolars than in molars and that the chance of an
      incipient lesion to remain undetected is twice as high in molars than in
      premolars.

PMID- 8990681
TI  - Interpretation of bitewing radiographs. Part 2. Evaluation of the size of
      approximal lesions and need for treatment.
AB  - OBJECTIVE: The decision to treat initial approximal carious lesions is based
      mainly on interpretation of bitewing radiographs. In a previous report, it was
      shown that artificial approximal lesions of uniform size are more readily
      detected on radiographs in premolars than in molars. The objective of the present
      study was to compare the ability to evaluate the depth of similar size artificial
      lesions on radiographs and reach decisions concerning treatment, in premolars and
      molars. METHOD: Clinicians were asked to evaluate on radiographs, the size of in
      vitro prepared artificial lesions, and decide at which point they would perform a
      restoration. RESULTS: Significant differences were found in the evaluation of
      lesion depth between different tooth surfaces. The interaction between lesion
      depth and tooth surface originated from the examiners' trend to score same size
      lesions as penetrating deeper into the tooth in premolars than in molars. The
      probability of the examiners to decide on restorative treatment in shallow
      lesions (0.25 mm, 0.50 mm) was higher in premolars than in molars. CONCLUSIONS:
      The findings suggest that clinicians evaluate initial lesions as being deeper and
      more prone to treatment in premolars than in molars.

PMID- 8990682
TI  - Marginal breakdown of 5-year-old direct composite inlays.
AB  - OBJECTIVES: The marginal fit of tooth-coloured inlays luted with composite resin
      luting materials has been considered to be the weak link of the inlays. The
      marginal breakdown of 5-year-old direct composite resin inlays was evaluated by
      scanning electron microscopy. METHODS: Replica impressions were made of the
      occlusal, axial-proximal and accessible cervical-proximal margins of 21 inlays
      and the marginal quality was quantified. RESULTS: More than 84% of the total
      investigated length of the enamel/luting composite agent-luting
      composite/composite inlay interfaces revealed gap free margins. Proximal margins
      showed the largest breakdown at the enamel/composite resin interface, while the
      occlusal margin interfaces showed only a slight difference between the
      interfaces. The composite inlay and the luting composite resin showed a similar
      degree of wear in more than 50% of the evaluated marginal length. Medium gap
      width varied between 60 microns for the occlusal and axial-proximal and 87
      microns for the cervical-proximal margins, with a range of 7.6-266 microns.
      CONCLUSIONS: The direct composite inlays investigated showed good marginal
      integrity after 5 years in clinical service.

PMID- 8990683
TI  - Demineralization effects of 10 percent carbamide peroxide.
AB  - OBJECTIVES: The purpose of this in vitro study was to measure the amount of
      calcium lost from enamel exposed to a 10% carbamide peroxide solution. METHODS:
      Nine teeth (3 incisors, 2 premolars, 4 molars) were sectioned to serve as paired
      test and control specimens. Each tooth half was coated with wax, leaving a
      uniform 3 mm x 4 mm window of exposed enamel. Test specimens were placed in
      culture tubes with 1.00 ml of deionized water and 0.02 ml of 10% carbamide
      peroxide for 6 h; controls were exposed to water alone. Calcium concentrations in
      the solutions were measured using a Perkin-Elmer 5100 atomic absorption
      spectrophotometer. RESULTS: Teeth exposed to carbamide peroxide lost an average
      of 1.06 micrograms/mm2 of calcium. This amount of loss was significantly greater
      than controls (p < 0.001), according to ANOVA. For comparison, teeth were exposed
      to a cola beverage for 2.5 min, the time equivalent of drinking a 16 oz.
      beverage. The amount of calcium lost from these teeth was also about 1
      microgram/mm2. CONCLUSIONS: Teeth exposed to 10% carbamide peroxide lost calcium.
      However, the amount of loss was small, and may not be clinically significant.

PMID- 8990684
TI  - A clinical comparison of a light cured glass ionomer sealant restoration with a
      composite sealant restoration.
AB  - OBJECTIVE: To compare the durability of a minimal composite sealant restoration
      (MCR) with that of a glass ionomer sealant restoration (GSR). METHODS: Under
      local anaesthesia, a MCR and a GSR were placed in the mouths of selected
      patients; allocation of restoration type was made randomly. All restorations were
      placed by one operator using standard procedures and were then assessed
      clinically at baseline and thereafter every 6 months. RESULTS: Fifty-eight
      patients, with a total of 66 pairs of restorations, were reviewed for up to 27
      months. Assessment criteria were based upon the amount of sealant lost, the state
      of the pit restoration and the occurrence of caries. There were no cases of
      recurrent caries, and a total of only four pit restorations failed, three (4.5%)
      GSRs and one (1.5%) MCR. Three MCRs and seven GSRs required further additions of
      sealant. Survival analysis was carried out using the loss of more than a third of
      the sealant as the failed status. At this level, the MCRs had a significantly
      greater Median Survival Time (MST) (24.7 months) than the GSRs (20.7 months) (p <
      0.05). Only seven (10.6%) of the MCRs lost more than a third of their sealant as
      compared with 17 (25.8%) of the GSRs. CONCLUSIONS: There was no significant
      difference in the durability of the MCR compared with the GSR in the treatment of
      occlusal caries. However, there was significantly better retention of the fissure
      sealant over the composite restoration than over the glass ionomer.

PMID- 8990685
TI  - Resistance to fracture of teeth with various preparations for amalgam.
AB  - OBJECTIVES: Advances in dental instrumentation and materials have allowed for
      increasingly conservative preparations when treating teeth for dental caries.
      Research has shown that some materials, properly used, can restore teeth to their
      pre-prepared strength. At the present time, the longevity of these materials is
      unknown, requiring clinicians to remain committed to conservative methods of
      tooth preparation. The purpose of this study is to compare the resistance to
      fracture of teeth prepared with occlusal, mesio-occlusal-distal (MOD) and
      mesial/distal slot preparations against unprepared control teeth. METHODS: Thirty
      two non-carious, non-restored human maxillary premolar teeth were divided into
      three experimental groups and a control group with eight teeth in each. After
      preparation, the teeth were loaded to fracture on an Instron Universal Testing
      Machine, and the results were compared using an Analysis of Variance (ANOVA)
      followed by Tukey's Studentized Range Test (P < 0.05). Fracture patterns were
      compared by chi-square analysis at the 0.1 level of probability. RESULTS: There
      was no significant difference in fracture resistance among the experimental
      groups, but all were less resistant to fracture than the unprepared control
      group. The MOD and occlusal groups demonstrated a tendency towards vertical
      fracture while the mesial-distal slot and unprepared groups tended to a more
      limited fracture of a single cusp. CONCLUSIONS: Any preparation appears to
      decrease a tooth's resistance to fracture. Conservative preparation design may
      affect fracture pattern and enhance options for subsequent restoration.

PMID- 8990686
TI  - SEM observations of the reactions of the components of a light-activated glass
      polyalkenoate (ionomer) cement on bovine dentine.
AB  - OBJECTIVES: Glass ionomer cements are used in clinical dentistry as lining,
      luting and restorative materials. The precise nature of their bonding mechanism
      to dentine is unclear. This study is an SEM examination of the effect of the
      liquid contained in Vitrebond cement (3M Co., MN) on the surface of bovine
      dentine, with respect to delays in photocuring and washing off with water under
      pressure or as a gentle stream. The effects of delaying photocuring of the mixed
      and applied cement for up to 120 s were also examined. RESULTS: The results of
      this study demonstrated that the liquid component of Vitrebond reacts chemically
      with dentine in a manner suggestive of an effervescent chemical reaction. This
      reaction produces plugs in the dentinal tubules which are resistant to
      dislodgement by water under pressure or by gentle washing. Similarly, a delay in
      photocuring the mixed and applied cements results in porosity of the cement at
      the dentine interface. CONCLUSION: The findings in this study suggest that the
      adhesion of Vitrebond to dentine is primarily chemical in nature and that its
      mechanical strength is compromised if there are substantial delays in
      photocuring.

PMID- 8990687
TI  - Spectroscopic changes in human dentine exposed to various storage solutions-
      short term.
AB  - OBJECTIVES: Tooth storage conditions in studies of dentine have not been
      standardized. The objective of this investigation was to determine the effects of
      storage solution and time on dentine, using spectroscopic methods. METHODS:
      Twenty-seven dentine disks (0.75 mm thick) were prepared from freshly extracted
      third molars with documented histories. The teeth were sectioned parallel to the
      occlusal plane using a diamond saw. Specimens were analysed non-destructively for
      surface chemical changes using specular reflectance infra-red Fourier transform
      spectroscopy (SRIFTS), and changes in optical properties were measured in the
      ultraviolet, visible and near-infra-red spectral ranges with an integrating
      sphere spectrophotometer (UV/VIS/NIR) before and after storage. A minimum of five
      specimens were stored in distilled water with 0.02% thymol, purified and filtered
      water, phosphate buffered saline with 0.02% thymol, 70% ethanol or 10% buffered
      formalin and evaluated at 0, 1, 2, 7, 14, 21 and 28 days. After each measurement,
      specimens were stored in fresh solutions. IR spectra were obtained from 4400 to
      400 wave-numbers (cm-1). Optical properties of reflectance and transmittance were
      determined from 200 to 2500 nm, and absorbance was calculated. RESULTS: Analysis
      of the IR spectra indicated no significant differences in collagen or mineral
      peak positions for any solution at any time period. There were significant
      differences in peak intensities of dentine stored in distilled water, purified
      and filtered water and phosphate-buffered saline over time in the IR spectra.
      Furthermore, differences in optical properties of dentine disks were detected by
      UV/VIS/NIR. CONCLUSION: It was concluded that changes in surface chemistry and
      optical properties of dentine occur as a function of storage solution and time,
      which must be considered when studying dentine.

PMID- 8990688
TI  - The influence of absolute humidity on shear bond adhesion.
AB  - OBJECTIVES: The purpose of this study was to investigate the relationship between
      dentine shear bond strength, using data from experiments performed according to a
      standard protocol, and the absolute humidity for a new, fourth generation dentine
      adhesive system. METHODS: Results of seven recently performed adhesion
      experiments using the same protocol and product were analysed. Groups of 10 human
      molars were each bonded in a humidity chamber. The temperature and relative
      humidity conditions varied from 23 to 37 degrees C and 30 to 95%. After bonding
      of the composite resin a shear bond test at a crosshead speed of 2.0 mm/min was
      performed. RESULTS: The bond strength levels of the dentine adhesive system were
      influenced significantly by extreme temperature and humidity differences.
      Adhesion levels varied from 27.8 (SD 8.5) MPA to 12.8 (SD 1.4) MPA. Isobond
      strength curves are a good method to gain insight into the humidity sensitivity
      of adhesive systems. CONCLUSIONS: Results of in vitro adhesive bonding procedures
      for a dentine adhesive can be significantly influenced by the absolute humidity
      levels at which the procedures are performed. Consequently "Materials and
      Methods" sections of publications should refer to absolute humidity or
      temperature and relative humidity levels as a relevant parameter.

PMID- 8990689
TI  - Effects of hexafluorosilicate on the precipitate composition and dentine tubule
      occlusion by calcium phosphate.
AB  - OBJECTIVES: To improve the calcium phosphate precipitation (CPP) method for the
      occlusion of dentine tubules with calcium phosphate, the addition of calcium
      hexafluorosilicate (CaSiF6) to CPP solution was evaluated in vitro with respect
      to its occluding capacity and the composition of the precipitate. METHODS: The
      occlusion of dentine tubules was evaluated by SEM observations and by
      measurements of dentine permeability. The composition of the precipitate was
      determined by measuring the calcium to phosphorus (Ca/P) ratio of the precipitate
      in dentine tubules by energy dispersive X-ray spectroscopy (EDS). RESULTS: The
      addition of CaSiF6 to the CPP solution resulted in an increase of the Ca/P ratio
      in the precipitate not only on the dentine surface but also inside the dentine
      tubules; indicating that the precipitate became more apatitic in nature. The
      addition of CaSiF6 had no effect on occluding capacity in terms of measurements
      of dentine permeability or SEM observations. Dentine permeability decreased to
      approximately 4% of pretreatment values and the dentine tubules were occluded for
      approximately 10-15 microns from the dentine surface. CONCLUSION: It is concluded
      that the addition of CaSiF6 to CPP solution was desirable, since it provided a
      more apatitic precipitate in the dentine tubules, not only on the dentine surface
      but also inside the tubules, and there were no drawbacks with respect to its
      occluding capacity.

PMID- 8990691
TI  - Thermographic assessment of dentine pin placement.
AB  - OBJECTIVE: This in-vitro study aimed to examine the change in surface temperature
      induced by the actions of drills for the placement of dentine pins. METHODS: Ten
      decoronated extracted premolar teeth were embedded by the apical tip of their
      roots in orthoresin. They were held in a bench vice and allowed to reach the
      ambient temperature of 24 degrees C. A thermal imaging camera, Agema Thermovision
      900 series, was positioned 0.05 m perpendicular to the decoronated surface.
      Sequential recording of a series of images was stored at a rate of three per
      second during each stage of the pin placement procedure. This included a pilot
      drill, a channel cutting drill and the pin placement. All pins were 0.675 mm
      diameter x 2 mm in length and were placed 1 mm from the amelo-dentinal junction
      using a Kavo handpiece rotating at 4000 rpm. RESULTS: The mean baseline
      temperature for the thermally stabilized teeth was 23.9 degrees C. The action of
      the round pilot drill changed the temperature from baseline by 25 degrees C. The
      action of the channel drill generated the greatest heat, with a mean maximum
      temperature recorded during these procedures of 94 degrees C +/- 9 degrees C. The
      pilot drill produced a mean change from baseline of 31.3 degrees C +/- 17.7
      degrees C during pin placement. CONCLUSIONS: The placement of dentine pins
      produced a high temperature increase on the surface of the dentine. All stages of
      pin placement gave rise to an increased temperature, but this was maximal with
      the channel drill. Further studies are required to determine whether these
      surfaces temperatures are transferred to the pulpal chamber.

PMID- 8990690
TI  - Regional bond strengths of resins to human root dentine.
AB  - OBJECTIVES: The demand for restoration of root dentine defects such as cervical
      erosion and root caries has significantly increased recently, but there is
      limited information on the performance of the adhesive resins to radicular
      dentine. The purpose of this study was to measure the regional tensile bond
      strength (TBS) of composite bonded to human root and coronal dentine, and to
      observe the interface between resin and root dentine by SEM. METHODS: Human
      extracted cuspid teeth were used to measure TBS with a new microtensile bond
      test. Enamel and cementum were removed from the labial tooth surfaces to form a
      long cavity preparation into dentine from the mid-crown to the apex of the root
      within the same tooth. All Bond 2 (all etch technique) or Imperva Bond (no etch)
      was bonded to dentine surfaces and covered with Protect Liner resin composite.
      The resin-bonded teeth were serially sliced into 16 sections at right angles to
      the long axis of the tooth, and the bonded surfaces were trimmed to give a bonded
      surface area of 1 mm2 for TBS testing. RESULTS: All Bond 2 bond strengths to
      coronal and apical dentine showed high values (23.5 MPa) but the bond strength
      was significantly lower on cervical root dentine. Imperva Bond produced a
      relatively high tensile bond strength to all regional areas. SEM showed that the
      thickness of the resin-infiltrated layer formed by All Bond 2 in root dentine was
      less than coronal areas. Resin infiltration with Imperva Bond was always less
      than 0.5 micron. The results suggest that high TBS values can be obtained with
      minimal resin infiltration in root dentine.

PMID- 8990694
TI  - Histamine: the quintessential mediator.
AB  - Histamine is unique in being the only substance described to date which fulfils
      all of the criteria established by Dale for an inflammatory mediator. Thus,
      histamine is known to cause the "Triple Response" of Lewis and to act via H1 and
      H2 receptors to produce vasodilation and increased vascular permeability;
      elevated levels of histamine are found in inflamed tissue; histamine is produced
      and stored in mast cells and there are established mechanisms for histamine
      release via mast cell surface receptors; and antihistamines alleviate the
      clinical manifestations of histamine release. There have been several recent
      advances in our understanding of histamine pharmacology and of the
      pathomechanisms of chronic idiopathic urticaria (CIU), a disease in which
      histamine plays an important role. Two new histamine receptors have been
      identified, the inhibitory (H3) receptor and the intracellular (H(ic)) receptor
      involved in cell proliferation. There is now evidence that mast cell derived
      histamine release in patients with CIU is due to an autoimmune disease, mediated
      by autoantibodies to the alpha-subunit of the high affinity IgE receptor on mast
      cells and basophils. Removal of these autoantibodies by plasmapheresis, or
      treatment with intravenous immunoglobulins may cause clinical remission.
      Cyclosporin A has also been found to be of benefit to some patients with CIU
      probably due to a mast cell "stabilising" effect, leading to reduced release of
      histamine and other mediators. This article reviews our current knowledge on
      histamine, its role, receptors and mechanisms for release.

PMID- 8990693
TI  - Dermatology 1945-95: the golden age of treatment.

PMID- 8990692
TI  - Shear bond strengths of two commercially available dentine-amalgam bonding
      systems.
AB  - OBJECTIVES: The purpose of this in vitro study was to determine the shear bond
      strengths (SBS) of amalgam to dentine treated with the Amalgambond Plus System
      (AM) and All-bond 2 System (AL) after storage periods in physiological saline for
      up to 48 weeks. METHODS: The occlusal superficial dentine surfaces of 150
      extracted human molars were exposed by wet grinding on 600-grit silicon carbide
      and the bonding area demarcated with a perforated adhesive tape. Freshly mixed
      Tytin amalgam was transferred to the opening in a split Teflon mold on the
      demarcated dentine surfaces treated with either AM or AL as directed by the
      manufacturers. The SBS of AM after 24 h (A), 4 weeks (B), 12 weeks (C), 24 weeks
      (D), and 48 weeks (E), and of AL after 24 h (F), 4 weeks (G), 12 weeks (H), 24
      weeks (I), and 48 weeks (J), were determined with a knife-edged rod at a
      crosshead speed of 0.5 mm/min and expressed in megapascal (MPa). The data were
      analyzed by ANOVA and Student's t-test. RESULTS: The mean +/- SD of SBS in MPa
      were: A: 14.6 +/- 4.0; B: 14.5 +/- 3.6; C: 15.3 +/- 4.8; D: 14.6 +/- 4.6; E: 13.9
      +/- 4.0; F: 9.5 +/- 4.7; G: 12.1 +/- 1.7; H: 10.2 +/- 3.5; I: 12.0 +/- 3.9; J:
      11.9 +/- 3.5. The SBS of the five groups treated with AM (A, B, C, D and E) were
      not significantly different (P > 0.05) and the SBS of the five groups treated
      with AL (F, G, H, I and J) were not significantly different (P > 0.05). The SBS
      of A vs. F, B vs. G, ad C vs. H, were significantly different (P < 0.05), but D
      vs. I and E vs. J were not significantly different (P > 0.05). CONCLUSION: The
      SBS of amalgam to dentine treated with AM and AL were not adversely affected by
      the duration of storage.

PMID- 8990695
TI  - The utility of transgenic mouse models in the study of cutaneous immunology and
      inflammation.

PMID- 8990697
TI  - Signal transduction in normal and neoplastic keratinocytes.

PMID- 8990696
TI  - Pigmented lesions of the conjunctiva.

PMID- 8990698
TI  - The stratum corneum revisited.

PMID- 8990699
TI  - Mastocytosis: new understandings in cutaneous pathophysiology.
AB  - Human mast cells contain large quantities of chymotryptic and tryptic
      proteinases. In human skin, mast cells contain both chymase and tryptase,
      whereas, in the mucosa of the gastrointestinal tract, mast cells contain
      primarily tryptase. By contrast, submucosal mast cells in the gastrointestinal
      tract are of the connective tissue type because they contain both chymase and
      tryptase. Chymase has a broad array of biological functions which include;
      activation of angiotensin, cleavage of basement membrane through the lamina
      lucida, activation of IL1 beta, and potentiation of histamine. Chymase may play a
      significant role in the control of a variety of biological phenomena. Urticaria
      pigmentosa is a disease characterized by deposition of "normal" connective tissue
      mast cells within the skin. The source of these mast cells is the bone marrow and
      mast cells appear to be deposited within other internal organs in almost all
      cases. Excretion of histamine and prostaglandin metabolites correlates with the
      deposition of mast cells in extracutaneous sites. High potency steroids under
      occlusion for six week results in long-lasting clearing of the cutaneous lesions
      with minimal side effects.

PMID- 8990700
TI  - Electron microscopy in AIDS-related infectious diseases. I. Acanthamoebiasis.

PMID- 8990701
TI  - Laser medicine in dermatology.

PMID- 8990702
TI  - Sunscreens: progress and perspectives on photoprotection of human skin against
      UVB and UVA radiation.

PMID- 8990704
TI  - An update of the benign proliferative monocyte-macrophage and dendritic cell
      disorders.

PMID- 8990703
TI  - Education continuum in Canadian dermatology.

PMID- 8990705
TI  - The skin cancer cascade: from ozone depletion to melanoma--some definitions and
      some new interpretation, 1996.

PMID- 8990706
TI  - Multiple basaloid cell hamartoma with alopecia and autoimmune disease (systemic
      lupus erythematosus).
AB  - We report a 22-year-old Japanese woman with multiple basaloid cell hamartoma with
      alopecia and autoimmune disease (systemic lupus erythematosus). She presented
      with infiltrated large annular, brown-violet, erythematous plaques with atrophic
      areas in the center on her right cheek, left abdomen and left knee. She also had
      progressive multiple follicular keratotic papules on her scalp, face, neck, and
      both axilla and hair loss from her scalp, eyebrow, and axilla. Serologically,
      rheumatoid factor (+ + +), rheumatoid arthritis hemagglutination test (x1280),
      and anti-nuclear antigen (x160) were positive. Histological findings of the
      annular lesion showed liquefaction degeneration of basal cells, lymphocytic
      infiltration around hair follicles and capillaries, and panniculitis with
      lymphoid cell infiltration, which was diagnosed as lupus erythematosus profundus.
      The histological findings of multiple follicular papular lesions of the scalp and
      neck showed aggregations of basaloid cells, partially with hair-bulb-like
      structures, which was diagnosed as trichoepithelioma. Taken together, the
      histogenesis of multiple basaloid cell hamartoma is thought to share the same
      basis with autoimmune disease.

PMID- 8990707
TI  - Atypical melanosis of the foot.
AB  - We present a case of a seemingly malignant pigmented lesion on the foot, arising
      in a Japanese female. Clinically, the lesion was characterized by irregular
      borders and variegated pigmentation closely mimicking those of acral lentiginous
      melanoma in situ. However, the histologic findings revealed only focal, slight,
      melanocytic hyperplasia with minimal cytologic atypia along the basal layer.
      Despite the malignant clinical features, thorough histologic examination failed
      to disclose any area with significant melanocytic atypia or evidence of
      malignancy. To the best of our knowledge, no similar lesions with the clinical
      appearance of melanoma in situ and completely lacking histologic evidence of
      malignancy have been reported. We, therefore, prefer to designate this lesion as
      atypical melanosis of the foot, to highlight the clinically atypical findings and
      to distinguish this from malignant melanoma in situ of the foot (1).

PMID- 8990708
TI  - Multiple nodular lesions seen in a patient with neurocutaneous melanosis.
AB  - Neurocutaneous melanosis is a rare congenital syndrome characterized by the
      presence of large or multiple congenital melanotic nevi and benign or malignant
      pigment cell tumors of the leptomeninges. A 2-month-old female infant was
      referred to our department with widespread pigmented nevi, numerous blackish
      brown, elevated, firm nodules, eye lesions, temporal bone defect, and generalized
      convulsion. The sizes of the nodules were from 0.5 to 3 cm; they were either
      white, black, brown or red, and some of them were eroded and bleeding. Magnetic
      resonance imaging using gadolinium contrast (MRI-Gd) demonstrated hydrocephalus,
      defect of the temporal bone, and T1-short and T2-long areas near the cerebrum and
      the thoracic vertebra (Th 4-5), suggesting the presence of melanosis in the
      central nervous system. Biopsy specimen of a firm, black nodule of a pigmented
      lesion on her shoulder revealed sheets of nevomelanocytes in the dermis with a
      few mitoses and large atypical cells that were positive for HMB-45 and
      formaldehyde-induced green specific fluorescence. Although this histological
      architecture is compatible with that of congenital nevi, occasional occurrence of
      atypical mitoses in the dermis may constitute an early stage of malignant
      melanoma. To make a definite diagnosis, however, long-time follow-up and repeated
      skin biopsy are considered necessary.

PMID- 8990709
TI  - Congenital atrophic plaque.
AB  - The patient is a 13-year-old female who had had a patchy lesion on her back since
      birth which increased in size proportional to her age. When she visited our
      hospital at the age of 13, the lesion was a 30 x 43 mm, slightly depressed, well
      defined, irregularly shaped, atrophic plaque. Differential clinical diagnoses at
      that time included macular atrophy, congenital melanocytic nevus, and
      mastocytosis. Histopathologically, the lesion was characterized by patchy and
      scattered infiltrates of oval to spindle cells throughout the dermis extending
      into the subcutaneous fat tissue. Nerve fibers were found in each of the
      infiltrates. The tumor cells had oval nuclei with relatively abundant cytoplasm
      and were similar to nevus cells. They were negative for markers such as S-100
      protein, neuron specific enolase, epithelial membrane antigen, HMB-45, Leu 7,
      Desmin, and alpha smooth muscle actin. However, the histopathological findings
      suggest that the lesion is a melanocytic or neurogenic tumor, possibly a
      congenital melanocytic nevus or a cellular neurothekoma, though a definite
      diagnosis could not be made.

PMID- 8990710
TI  - A case of subcutaneous malignant fibrous histiocytoma circumscribed by fibrous
      tissue.
AB  - We report a case of malignant fibrous histiocytoma (MFH) located in the
      subcutaneous tissue on the right axilla. We excised the tumor sufficiently beyond
      the clinical margin. It was pathologically diagnosed as a storiform-pleomorphic
      type of malignant fibrous histiocytoma almost completely circumscribed by fibrous
      tissue, including fascicles of fibroblasts; this is a rare histological picture.
      The tumor has not recurred for three years. Although MFH frequently undergoes
      metastasis, the circumscribed-type subcutaneous MFH characteristic of
      superficiality and of histologically well-defined structure seems to have a
      relatively more favorable prognosis after adequate radical excision.

PMID- 8990713
TI  - Nurse-midwives and domestic violence.

PMID- 8990711
TI  - Lentiginous melanocytic hyperplasia overlying dermatofibroma.
AB  - There are occasional reports of proliferative epidermal changes overlying
      dermatofibromas. We report the first case to our knowledge of a dermatofibroma
      with overlying lentiginous melanocytic hyperplasia.

PMID- 8990714
TI  - Domestic violence. Implications for the American College of Nurse-Midwives and
      its members.
AB  - Domestic violence, as well as other forms of violence against women, has received
      increased attention from many sectors of society in the past two decades.
      Estimates that one fourth to one half of all women in the United States are
      victims of some type of violence are startling. There exists today a broad-based
      recognition of and response to the impact of violence on the workplace, the
      health care community, and the woman survivor and her children. Public health,
      corporate, and government initiatives are actively seeking solutions to address
      this most destructive dynamic. The education of health care providers to assess
      women appropriately for the potential of abuse-including proper intervention,
      documentation, and referral-has become an essential component of health care. As
      a recipient of a 3-year federal grant to educate students and practicing nurse
      midwives in the United States about the issue of domestic violence, the Special
      Projects Section of the American College of Nurse-Midwives (ACNM) has joined the
      ranks of concerned provider organizations. The primary goal of the project is to
      promote and enhance universal screening of all women who present for midwifery
      care. The role of the certified nurse-midwife and other women's health care
      providers and the role of ACNM in responding to the issue of domestic violence,
      including future goals and expectations, are discussed.

PMID- 8990715
TI  - Woman abuse. The role of nurse-midwives in assessment.
AB  - When health care providers do not assess routinely for abuse, it most likely is a
      result of the powerful social myths surrounding domestic violence and a lack of
      knowledge about incidence, prevalence, and the dynamics of abuse. This article
      examines commonly held myths as well as personal and social constraints that
      cause practitioners not to assess for abuse. Additionally, it presents guidelines
      for the assessment of individual women, as well as professional role development
      in the area of abuse of women and suggests that nurse-midwives are generally well
      positioned to assess their clients for the health problems of violence and abuse.

PMID- 8990716
TI  - Sequelae of abuse. Health effects of childhood sexual abuse, domestic battering,
      and rape.
AB  - Violence against women is endemic in the United States. One third to one half of
      all women will experience one or more types of abuse in their lifetime, most
      often at the hands of a family member or an intimate or formerly intimate
      partner. One in 12 women is battered during pregnancy. Abuse survivors are
      disproportionately frequent users of health care services because of acute and
      chronic physical, somatic, emotional, and behavioral sequelae of abuse. Health
      care practitioners are often the first contact abuse survivors have with a
      potentially helping professional. It is, therefore, essential that health care
      providers learn to identify and to intervene appropriately with survivors of
      abuse. This article reviews and compares the health effects of three of the most
      common types of violence against women: childhood sexual abuse, domestic
      battering, and rape. Sequelae are divided into six categories: physical/medical,
      somatic, emotional/ psychological, social/interpersonal, behavioral/sexual, and
      pregnancy-related effects. The health effects discussed in this article include
      research findings, as well as effects noted in clinical practice. Recommendations
      are made for routine screening of all women for past and current abuse, as well
      as for intervention strategies.

PMID- 8990717
TI  - Cultural competence in the care of abused women.
AB  - This article explains the concept of cultural competence, adding advocacy to
      models of culturally competent health care already in the literature and
      demonstrating how it relates to domestic violence. Abuse stages according to
      Landenburger's model of entrapment and recovery are presented with applicable
      cultural differences and specificities. Cultural issues related to specific
      childbearing-stage abuse interventions are also discussed. The principles of
      cultural competence, abuse- and childbearing-stage specificity, and empowerment
      are used as the basis for this model of clinical intervention with abused women.

PMID- 8990718
TI  - Unheard and unseen. Rural women and domestic violence.
AB  - Rural society and conditions can contribute to make domestic violence more
      difficult to escape. Physical and social isolation, the distance to and
      unavailability of services, and rural culture provide challenges to abused women
      and to health care providers that are different from the obstacles seen in better
      studied urban areas. Heightened awareness can aid in identification of abuse.
      Social action is necessary to change communities and to interrupt the cycle of
      violence.

PMID- 8990719
TI  - Forensic documentation of battered pregnant women.
AB  - Patients hurt during intimate partner abuse are crime victims who may seek legal
      relief and protection from one or more court systems. What the health care
      provider documents or does not document may have tremendous forensic
      implications; yet, most health care providers have received little formal
      training in clinical forensics. Being subpoenaed to court as a witness can
      trigger fear and anxiety. This article reviews the basic principles of clinical
      forensic documentation, evidence collection and preservation, forensic
      photography, and accurate wound identification, as well as tips on working with
      police and on testifying in court.

PMID- 8990720
TI  - Effective advocacy for domestic violence victims. Role of the nurse-midwife.
AB  - A nurse-midwife may be one of the first professionals domestic-abuse victims talk
      to about the abuse. Like other health professionals who see abuse victims for
      health issues often unrelated to abuse, nurse-midwives have a special opportunity
      to identify, intervene, and support victims of domestic violence. Professionals
      working in health care will see abuse victims when they are living with their
      abusers and do not know that abuse is abnormal, when they attempt to leave their
      abusers, when they return to their abusers, and when they ultimately separate.
      Justice system professionals only see abuse victims when they have decided to try
      to leave. A thorough knowledge about relief available in the legal system for
      abuse victims will allow nurse-midwives to help battered women effectively. This
      article discusses the role nurse-midwives should play in assisting abuse victims
      who will be seeking help from the civil and criminal justice systems. Topics
      discussed include the importance of documenting injuries for use in future court
      cases, civil protection orders, criminal court prosecutions of the abuser, legal
      malpractice issues if health providers do not identify battered women, informing
      and referring domestic-violence victims, and the special needs of immigrant
      women. The article also discusses typical problems victims encounter in the legal
      system and ways victims can overcome these barriers.

PMID- 8990723
TI  - Cardiorespiratory reactivity during the Brazelton Scale in term and preterm
      infants.
AB  - Determined the relationship between behaviour measured with the Brazel zelton
      Scale and simultaneously recorded cardiorespiratory activity. The Brazelton Scale
      was administered and videotaped in a sample of 22 term and 22 preterm infants at
      term conceptional age. The videotapes were coded off line with a computer
      interface to time lock behavior and physiological activity for the duration of
      four alert, non-crying conditions. Term infants showed increases in heart rate
      and breathing rate when unswaddled and cuddled following cry and increases in
      respiratory sinus arrhythmia (RSA) during orientation and swaddling. Preterm
      infants showed the same general trend as term infants in heart rate and breathing
      rate. However, RSA decreased during orientation in preterm infants. On behavioral
      scores, preterm infants showed lower scores on self-regulation and a higher cost
      of attention. Correlations between behavior and physiological activity showed
      lower RSA associated with enhanced behavioral scores for the preterm infants.
      Results of this study are consistent with the hypothesis that attentional
      responsivity in the preterm infant may be at the expense of physiological
      stability.

PMID- 8990721
TI  - High-risk infants.

PMID- 8990724
TI  - Behavioral sleep states in very low birth weight preterm neonates: relation to
      neonatal health and vagal maturation.
AB  - Assessed the relation of behavioral codes of quiet versus active sleep state to
      neonatal health status in 62 very low birth weight preterm neonates. Sleep
      sessions (12 min) were coded for percentage time in active versus quiet sleep at
      33, 34, and 35 weeks conceptional age. ECG was monitored during each sleep
      session to derive measures of heart rate, heart rate variability, and an index of
      cardiac vagal tone derived from respiratory sinus arrhythmia. Higher risk
      neonates spent more sleep session time in active sleep than healthier preterm
      neonates. Cardiac vagal tone showed a maturational change during the study weeks,
      whereas percentage of sampled sleep time in active sleep did not. Vagal
      maturation measured by age-related increases in the amplitude of respiratory
      sinus arrhythmia was associated with less active sleep overall, although weekly
      measures of respiratory sinus arrhythmia and sleep state were not related. Follow
      up data on 30 of the neonates indicated that heart rate variability and cardiac
      vagal tone, but not sleep state measures, were related to better outcomes in
      mental processing, social skills, and motor skills, and to fewer behavior
      problems. Results are discussed in terms of the lack of coupling between
      behavioral and physiological components of preterm sleep states at this age as
      compared with that seen in full-term sleep states.

PMID- 8990722
TI  - The Neurobehavioral Assessment Scale as an instrument for early long-term
      prognosis and intervention in major disability in high-risk infants.
AB  - Evaluated the hypothesis that more effective prognosis is achieved by assessing
      the modifiability of infants' reactions than by evaluating the presence or
      absence of normal/abnormal reactions. To evaluate this hypothesis the
      Neurobehavioral Assessment Scale (NAS) was developed. The NAS assesses the extent
      to which infants can change their responses in functional contexts. The NAS was
      administered to 102 high-risk infants repeatedly over the first 16 months of
      life. Analysis confirmed that the modifiability of performance was predictive of
      outcome significantly earlier in development than scoring the same items in terms
      of their normalcy or abnormalcy.

PMID- 8990725
TI  - Cry threshold predicts regulatory disorder in newborn infants.
AB  - Studied the autonomic regulation of 37 infants with a typical cry threshold and
      17 infants with a high cry threshold (typical of problems in nervous system
      function). Infants with a high cry threshold had a longer latency to cry, a
      shorter first cry sound, and a shorter overall bout of crying. Spectrum analysis
      of 2 hours of heart rate variability showed that a high cry threshold was
      predictive of fewer reliable rhythms and a lower power of the basic 40-min rhythm
      in heart rate. High cry threshold infants also showed fewer startles and changes
      in behavioral state. Results suggest a high cry threshold predicts disrupted
      autonomic regulation and poor coordination among rhythmic systems affecting
      cardiac activity.

PMID- 8990726
TI  - Arousal-modulated attention at four months as a function of intrauterine cocaine
      exposure and central nervous system injury.
AB  - CNS-compromised neonates are poor modulators tending to prefer less stimulation
      in all arousal conditions. Cocaine-exposed neonates also are poor modulators but
      tend to prefer more stimulation in all arousal conditions. Infants (N = 359, M =
      4 months) were divided into 6 CNS injury groups and 1 cocaine-exposed, non-CNS
      injured group and tested in three arousal conditions: less aroused (after
      feeding), more around-endogenous (before feeding), and more aroused-exogenous
      (after feeding with additional stimulation prior to each trial). Infants with CNS
      injuries still showed some degree of influence of arousal on attention that was
      now similar to that seen in normal neonates and 1-month-olds, while cocaine
      exposed infants, 4-month-old normal and mild or moderate CNS-injury infants did
      not.

PMID- 8990728
TI  - Effect of cerebral lesions on continuous performance test responses of school age
      children born prematurely.
AB  - Examined attention skills, as measured by the Continuous Performance Test (CPT),
      in a group of 64 children born premature and 40 full-term children, ages 6 to 8
      years. Premature children were classified by neonatal cerebral lesions into no
      lesion, mild lesion, and severe lesion groups. It was predicted that severity of
      lesion would be associated with CPT performance. While mean differences among the
      groups of prematures did not reach significance, children with severe lesions
      made significantly more errors of omission and commission than the full-term
      comparison group. Children with mild lesions were poorer than full terms in
      errors of commission. Children with no lesions also made more errors of omission
      and commission than full terms, suggesting attention deficits secondary to
      prematurity even in the absence of identified brain lesion. With increasing
      severity of lesion, increasing percentages of each group were found to perform
      more than 2 SD below the mean in errors of commission. Results suggest that
      premature children, with and without identified lesions, are at risk for
      attention deficits.

PMID- 8990729
TI  - Effects of Brazelton demonstrations on later parenting: a meta-analysis.
AB  - Meta-analysis of parenting interventions based on the Neonatal Behavioral
      Assessment Scale (NBAS) was conducted. Only published studies (n = 13) were
      included in this analysis, with one effect size entered for each study. The
      studies contained a total of 668 families, an average of about 51 per study.
      Effect sizes are reported in terms of the correlation coefficient (r) as well as
      the difference between experimental and control group means divided by the pooled
      standard deviation (Cohen's d). Analyses were conducted by weighting each study
      equally (unit weighting) and also by sample size. Similar average effect size
      were obtained for both weighting procedures (r's of about.2, d's of about.4),
      indicating that Brazelton-based interventions during the neonatal period have a
      small-moderate beneficial effect on the quality of later parenting. The
      probability of obtaining these findings by chance approached zero. The potential
      factors influencing these results are discussed, as well as directions for future
      research.

PMID- 8990727
TI  - Effect of prenatal alcohol and cigarette exposure on two- and six-month-old
      infants' adrenocortical reactivity to stress.
AB  - Examined the effect of prenatal alcohol and cigarette exposure on infant
      adrenocortical reactivity to stress at 2 and 6 months of age. Cortisol response
      (pre- to poststressor increase) at 2 months was lower for the exposed than
      nonexposed infants, whereas cortisol response at 6 months did not differ between
      the exposed and nonexposed infants. The 2-month group difference in cortisol
      response reflected a higher prestressor cortisol level in the exposed infants.

PMID- 8990730
TI  - Predictors of developmental outcomes for medically fragile early intervention
      participants.
AB  - Little is documented about the determinants of developmental outcomes for
      medically fragile infants who receive early intervention. In this controlled
      longitudinal study 65 premature infants with intraventricular hemorrhage (IVH)
      were randomly assigned to intervention groups beginning at 3 months adjusted age
      (Early) or 12 months adjusted age (Delayed). The sample was 65% African American
      and 35% Caucasian, and over half the youngsters were being raised by single
      mothers. Although cost analyses revealed that it was almost twice as expensive to
      begin sensorimotor intervention at the earlier age, annual comprehensive
      assessments revealed no significant differences in developmental outcomes based
      on age at start. Stepwise multiple regression analyses revealed that Maternal
      Education and Neonatal Medical Problems were significant predictors of outcomes
      at years 1, 3, 5, and 7 regardless of age at start. Related findings from other
      studies are discussed along with implications for policy and future research.

PMID- 8990731
TI  - Massage therapy improves behavior in neonates born to HIV-positive mothers.
AB  - Assigned randomly 28 neonates born to HIV-positive mothers to a massage therapy
      or control group. The treatment infants were given three 15-minute massages daily
      for 10 days. The massaged group showed superior performance on almost every
      Brazelton newborn cluster score and had a greater daily weight gain at the end of
      the treatment period unlike the control group who showed declining performance.

PMID- 8990732
TI  - Would you do it again?

PMID- 8990733
TI  - Foreign body aspiration.

PMID- 8990734
TI  - Gallium alloy.

PMID- 8990735
TI  - Infection control.

PMID- 8990736
TI  - Public vs. private schools.

PMID- 8990738
TI  - CyberNews.

PMID- 8990737
TI  - More on Nova University.

PMID- 8990739
TI  - A banner year for organized dentistry.

PMID- 8990740
TI  - The new OSHA: less visible, more effective.

PMID- 8990741
TI  - Meeting the challenges of changing times.

PMID- 8990742
TI  - Strength in numbers.

PMID- 8990744
TI  - Lateral cephalometric radiographs: an aid in detecting patients at risk of
      stroke.
AB  - Stroke is often caused by atherosclerotic lesions in the bifurcation of the
      common carotid artery. The authors evaluated conventional lateral cephalometric
      radiographs of 1,063 healthy men aged 25 to 85 years for the presence of such
      lesions. Approximately 2 percent of these people had lesions, which were at the
      level fo the third and fourth cervical vertebrae and were superimposed over these
      structures, the pre-vertebral fascia and the pharyngeal air space. People with
      atherosclerotic lesions should be referred to their physicians because timely
      medical, surgical and lifestyle interventions can prevent strokes.

PMID- 8990743
TI  - Detecting osteoporosis using dental radiographs: a comparison of four methods.
AB  - The authors evaluated dental radiographs for signs of osteoporosis using four
      methods: fractal dimension, microdensitometry, pixel intensity and panoramic
      analysis of cortical thickness. The efficacy of these methods also was compared
      against three standard bone density measurement techniques used to diagnose
      osteoporosis in bones other than the jaws: quantitative computed tomography and
      single- and dual-photon absorptiometry. Pixel intensity was significantly more
      effective than the other dental methods at distinguishing between radiographs
      from the osteoporotic group and the control group, although fractal dimension and
      microdensitometry methods also were effective.

PMID- 8990745
TI  - Resin-bonded fixed partial dentures: a review of three decades of progress.
AB  - The resin-bonded fixed partial denture has undergone significant changes in
      design, materials and tooth preparation since its development in 1973. The
      selection of resin cement and micromechanical retention have closely paralleled
      alloy-resin-bonding research. Despite impressive in vitro research results, only
      74 percent of the prostheses are still functional at the end of four years.
      Understanding the limitations, indications and design of resin-bonded fixed
      partial dentures will result in improved longevity and patient satisfaction.

PMID- 8990746
TI  - An accurate, time-efficient method to assess plaque accumulation.
AB  - The authors compared the accuracy and time efficiency of a simplified index
      called the Plaque Assessment Scoring System, or PASS, and the O'Leary Plaque
      Control Record. Using both indexes, they examined 35 participants. They found a
      strong correlation between the results achieved with each method. They also noted
      that the mean time required to complete the PASS examination was considerably
      less than that needed to record the O'Leary index, 1.47 vs. 7.07 minutes,
      respectively.

PMID- 8990748
TI  - A helping hand to youth.

PMID- 8990747
TI  - Motor vehicle accidents and TMDS: assessing the relationship.
AB  - Patients involved in a motor vehicle accident, or MVA, may experience signs and
      symptoms suggesting temporomandibular joint or masticatory muscle injury. Because
      there are no published clinical studies assessing the potential relationship
      among reported variables suggesting injury, examination findings, and crash
      impact and postural variables, the authors gathered data from 219 patients
      identifying TMD after an MVA. The results suggest that TMJ or masticatory muscle
      injury may be associated with varying postural characteristics and impact events,
      including speed, direction of impact and vehicular damage.

PMID- 8990749
TI  - Scheduling for productivity, profitability and stress control.
AB  - Scheduling is the heartbeat of the dental practice. You must control your days
      with effective scheduling or your days will control you. In this article, you
      will learn nine criteria that are essential in achieving smooth-flowing,
      productive days.

PMID- 8990750
TI  - A simple technique for adjusting a removable prosthesis.

PMID- 8990751
TI  - Can the thermal disinfector outperform the ultrasonic cleaner?

PMID- 8990752
TI  - Infection and immunity.

PMID- 8990753
TI  - Leptin: can it treat obesity?

PMID- 8990754
TI  - Alternatives to estrogen replacement therapy for preventing osteoporosis.
AB  - Osteoporosis is a leading cause of disability and death in older Americans; women
      are at higher risk than men. Bone is a living tissue that undergoes continuous
      remodeling throughout life. Several drugs-including sex hormones,
      bisphosphonates, calcitonin, and sodium fluoride-can arrest the progression of
      osteoporosis and prevent fractures. Calcium and vitamin D supplementation may
      prevent the development of osteoporosis in high-risk individuals and are useful
      adjuncts when used with other treatments.

PMID- 8990755
TI  - Pragmatic training program motivates practitioners.

PMID- 8990756
TI  - Impact of an executive-level management program.
AB  - Program teaches management skills beyond those taught in pharmacy school.
      Pharmacists benefit not only from educational growth but also from networking
      opportunities. Alumni report that the program has had a positive impact on their
      personal and career objectives, their department, and their organization.
      Involvement of administrators helps pharmacy directors take home solutions to
      specific problems for immediate implementation.

PMID- 8990757
TI  - Polypharmacy and the treatment of HIV/AIDS.

PMID- 8990758
TI  - Evaluating the outcomes of pharmaceutical care.

PMID- 8990759
TI  - Satisfaction with prescriptive authority protocols.
AB  - OBJECTIVES: The use of prescriptive authority protocols by pharmacists and
      physicians in Washington was described as to: (1) types of decisions made,
      frequency of use, and nature of working arrangements among participants; (2)
      their perceived impact on professional practice and care rendered to patients;
      and (3) their satisfaction with the protocol arrangements. DESIGN: A mail survey
      of participants currently engaged in prescriptive authority was conducted.
      RESULTS: Responses were received from participants in 44 of 57 protocols. A total
      of 135 prescribers and 84 pharmacists responded. On average, 7 pharmacists and 27
      prescribers were involved in each protocol, and had been involved for 6 years or
      more. It was estimated that approximately 10% of all active practitioners
      participated in protocols. Most protocols involved continuation of drug therapy
      or authorizing renewals. Modification of therapy (usually involving dosage or
      dose from changes) was practiced in two-thirds of the protocols, and initiation
      of therapy in about half of them. Most existed within managed care and group
      practice settings. Most prescribers (98%) and pharmacists (95%) were satisfied
      with protocol arrangements. Additionally, they generally agreed that the
      protocols increase patient convenience and increase the quality of patient care,
      and they encouraged their colleagues to use prescribing protocols. CONCLUSIONS:
      Protocol arrangements appear to be working well from the perspective of
      participants. Based on this experience, the authors encourage the development of
      similar protocol arrangements in other states.

PMID- 8990760
TI  - 1996 Podiatric Practice Survey. Statistical results. Al Fisher Associates, Inc.
AB  - This report presents the results of analyses of statistical data from 4,328
      members of the American Podiatric Medical Association (APMA) who responded to the
      1996 Podiatric Practice Survey, conducted from July through August 1996. Written
      comments from a sample of 200 respondents were also extracted for review and
      analysis.

PMID- 8990761
TI  - The sure proof. Wine is sure proof that God loves us and wants us to be happy.

PMID- 8990762
TI  - Changes in galactosemia screening program.

PMID- 8990763
TI  - Pseudomembranous colitis.

PMID- 8990764
TI  - A pulmonary monitoring and treatment plan for children with Duchenne-type
      muscular dystrophies.
AB  - The Pulmonary Medicine Section of the Department of Pediatrics of the University
      of Arkansas for Medical Sciences has recently developed an association with the
      Muscular Dystrophy Association Clinic held at Arkansas Children's Hospital. The
      slowly progressive, insidious onset of pulmonary problems associated with
      Duchenne-type muscular dystrophies and other degenerative muscle disorders
      indicated a need for a aggressive monitoring and treatment plan for these
      children and their caregivers. We have developed a Respiratory Care Handbook for
      families with information on the pulmonary consequences of these diseases
      including pathophysiology, pulmonary function tests, respiratory treatments
      including mechanical ventilatory support, and anticipation and prevention of
      pulmonary crises. In addition, we have introduced for the physician a formal
      monitoring and treatment regimen driven by changes in the vital capacity lung
      volume. The substance of this plan is presented in this manuscript.

PMID- 8990765
TI  - Adverse drug reactions.

PMID- 8990766
TI  - Radiological case of the month. Right coronary artery bypass graft aneurysm.

PMID- 8990767
TI  - Adaptation: a new concept in radiation biology and oncology and its clinical
      relevance.
AB  - A new concept of adaptation and cross-resistance in radiation biology and
      oncology is introduced. It explains the apparent difference in the
      radiosensitivity of cells of the same type (both normal and tumor) that are
      located in different parts of the body. Oxygen tension, which varies considerably
      from one part of the human body to another, ranges from 20 mmHg to 159 mmHg (2.7
      21%). When cells are adapted to live in areas with high physiologic oxygen
      tension (high normoxic) such as the epidermis and upper and lower airways, they
      develop better antioxidant mechanisms, which include free radical scavengers and
      DNA repair, than cells that live in lower physiologic oxygen tension (low
      normoxic). Because the mechanisms of cell-damaging effects of ionizing radiation
      are similar to those of oxygen, the cell that is resistant to oxygen toxicity
      also becomes resistant to ionizing radiation (and certain cancer chemotherapeutic
      agents). Based on this concept, it could be expected that some human tumors such
      as primary cutaneous malignant melanoma and lung cancers contain cells that are
      relatively resistant to ionizing radiation as a consequence of living in a high
      normoxic condition and the treatment of these tumors may require different
      strategies.

PMID- 8990768
TI  - Recent advances in the treatment of benign prostatic hyperplasia.
AB  - The prevalence of benign prostatic hyperplasia (BPH) in Taiwanese men over the
      age of 50 years is as high as those in Western countries. BPH significantly
      affects the life quality of patients. Many theories of the genesis of BPH have
      been reported and some effective treatments have been designed according to these
      theories. Adequate preoperative studies can lead to satisfactory treatment
      results. Medical treatments including alpha-adrenergic blockers and 5-alpha
      reductase inhibitors are frequently used as initial steps. Surgical treatment is
      necessary in more than one-quarter of patients in order to achieve good results.
      Transurethral resection of the prostate (TURP) remains the gold standard for
      treatment of BPH, although laser prostatectomy may become as popular as TURP in
      the future. Transurethral thermotherapy with microwave is also a promising new
      treatment. There are many other medical or surgical treatments under
      investigation. Further neuroendocrine research and studies with techniques of
      molecular biology may offer new concepts in BPH treatment in the future.

PMID- 8990769
TI  - Colonoscopic screening for families of patients with colorectal cancer.
AB  - We conducted a prospective study using primary colonoscopy in the families of
      patients with surgically treated colorectal cancer (CRC) to evaluate its
      feasibility as a screening method for CRC. The presumed detection sensitivity of
      sigmoidoscopy in this group was also evaluated. Over a 3-year period, 142 first
      degree relatives (73 men and 69 women) of 117 patients with CRC participated in
      this colonoscopic screening study. The average age at presentation for
      examination was 49.1 years (range, 31-79 yr). Forty-nine patients had adenomatous
      polyps (AP) and four patients had cancer, yielding a frequency of 37% (53/142).
      Thirty-six family members were under 40 years of age, eight of whom had AP. In
      total, there were 111 AP and four invasive cancers; 42% (48/111) of AP and 75%
      (3/4) of cancers were beyond the reach of conventional flexible sigmoidoscope. Of
      53 patients with AP or cancer in the large bowel, 36 had AP or cancer in the
      distal colon (rectosigmoid region and descending colon), 15 (42%) of whom were
      found to have at least one AP or cancer in the proximal colon (proximal to the
      descending colon). The remaining 17 patients' lesions were confined to the
      proximal colon, and would not have been detected with a flexible sigmoidoscope.
      Sigmoidoscopy in high-risk patients with neoplasm in the large bowel has a
      sensitivity of 68%. We conclude that a vigorous surveillance program using
      primary colonoscopy should be set up for those who are first-degree relatives of
      patients with CRC. Routine examination should start at the age of 40, and the
      entire colon should be evaluated.

PMID- 8990770
TI  - Therapeutic responses to corticosteroids in Graves' ophthalmopathy.
AB  - To elucidate the therapeutic responses to corticosteroids and prognostic factors
      in the treatment of Graves' ophthalmopathy, 23 patients with Graves'
      ophthalmopathy were treated with intravenous methylprednisolone 0.5 g daily for 3
      days, followed by prednisolone 40 mg daily. Dosage was reduced gradually to 10 mg
      daily over 4 weeks. The symptoms and signs of the eyes were recorded. Orbital
      computed tomography and urinary glycosaminoglycan excretion testing were
      performed before treatment. We observed the effectiveness of treatment at 6
      months as the endpoint of this study and classified the response as good or poor.
      We compared the differences in parameters between these two groups. The results
      showed that 12 (52%) out of 23 patients had a good response, and three (25%) of
      those with a good response recovered completely. Corticosteroid therapy
      dramatically improved lacrimation, reduced soreness and congestion of the eyes
      and ameliorated exophthalmos, lagophthalmos and extraocular muscle movement. Four
      (36%) of the 11 patients with a poor response had rebound of symptoms and/or
      signs after the dosage of prednisolone was decreased. Those with a good response
      were usually younger, and enlargement of the extraocular muscle was also milder
      than in those with a poor response. This study demonstrated that corticosteroid
      therapy is effective in Graves' ophthalmopathy and that extraocular muscle size
      demonstrated by orbital computed tomography is a prognostic factor of therapy.

PMID- 8990771
TI  - Intravenous immunoglobulin in the treatment of full-term and premature newborns
      with sepsis.
AB  - Blood cultures were performed on 141 newborn infants who had clinical features or
      laboratory data indicative of sepsis between January 1993 and April 1995.
      Clinical features included respiratory deterioration, poor activity, abdominal
      distension and apnea. Abnormal laboratory data included leukocytosis, leukopenia,
      elevated C-reactive protein values or increased immature neutrophil counts. The
      141 neonates with suspected bacterial infections received antibiotic therapy and
      were randomly divided into two groups. One group received a single dose of 500
      mg/kg of intravenous immunoglobulin (IVIG), while the other group received
      placebo (0.9% sodium chloride). Patients with negative blood cultures were
      excluded from this study. A total of 56 neonates with positive blood cultures
      were enrolled in this study. The IVIG-treated group and placebo-treated group
      consisted of 10 premature and 18 term neonates, respectively. Another 10 healthy
      premature and healthy 18 term neonates were selected as the control group. Serum
      IgG values increased significantly 1 and 2 weeks after administration of IVIG in
      the IVIG-treated group. However, there was no significant difference in the
      duration of treatment and mortality between the IVIG-treated and placebo-treated
      groups. Our preliminary observations suggest that administration of 500 mg/kg
      IVIG to neonates with sepsis had no effect on reducing mortality. In addition, it
      shortened neither the duration of antibiotic therapy nor hospitalization. No
      adverse reactions to the IVIG infusions were noted during the study.

PMID- 8990772
TI  - Clinical trial of low-dose rHuG-CSF in neutropenic cancer patients following anti
      cancer chemotherapy.
AB  - Low-dose, subcutaneous recombinant human granulocyte colony-stimulating factor
      (rHuG-CSF, Lenograstim) was administered to 40 cancer patients (17 men, 23 women)
      enrolled from two medical centers to verify its clinical effectiveness and
      safety. The patients' mean age was 50.3 +/- 14.9 years. In this study, there were
      20 patients with non-Hodgkin's lymphoma, 10 with breast cancer and 10 with
      various other solid tumors. The patients first received a course of chemotherapy
      without rHuG-CSF (control cycle). All patients had at least one episode of
      neutropenia or leukopenia during the control cycle. rHuG-CSF (2
      micrograms/kg/day) was given subcutaneously for 10 days during the study cycle
      starting on the fourth day of chemotherapy. The nadirs of absolute neutrophil
      counts (ANC) were 1.8 +/- 0.25 x 10(9)/L and 0.27 +/- 0.05 x 10(9)/L for the rHuG
      CSF cycle and pre-rHuG-CSF control cycle, respectively. The number of days of ANC
      < 1 x 10(9)/L were 1.03 +/- 0.29 and 7.38 +/- 0.58 for rHuG-CSF and control
      cycles, respectively. The duration from nadir to recovery of ANC (> or = 2 x
      10(9)/L) was 9.68 +/- 1.15 days in the rHuG-CSF cycle, vs 22.53 +/- 1.03 days in
      the control cycle (p < 0.0001). No patient withdrew from the study. Adverse
      events were mild, with 12.5% to 40% of patients developing myalgia, general
      malaise, back pain, anorexia or fever. These side-effects were tolerable in all
      cases. The biochemical abnormalities were subtle and negligible. rHuG-CSF 2
      micrograms/kg/day given subcutaneously for 10 days beginning on the fourth day of
      chemotherapy is very effective (90%), safe and convenient.

PMID- 8990773
TI  - Borderline malignant tumors of the ovary: study of prognostic factors.
AB  - A 16-year review of borderline tumors of the ovary was carried out to study the
      clinical features and outcomes of patients and to assess the value of color
      Doppler ultrasound in preoperative diagnosis. The records of 53 patients with
      borderline tumors of the ovary were retrospectively analyzed for clinical
      features, sonographic findings and survival. Twenty-three of 44 patients with
      stage I disease were treated conservatively without recurrence. Seven of eight
      (87.5%) patients with stage III disease developed recurrent or persistent tumors
      within 3 years. Overall, eight of 53 (15.1%) patients had recurrent or persistent
      disease. Twenty-three of 44 (52.3%) patients with borderline ovarian tumors
      showed morphologic malignancy by gray-scale sonography. Ten of 13 (76.9%)
      patients who had color Doppler ultrasound examination had detectable intratumoral
      blood flow. The mean resistance index value was 0.47 (range, 0.3-0.6). Three of
      these patients (30%) had a resistance index value < 0.4. The results indicated
      that the extent of disease as reflected by the clinical stage was the main factor
      for prediction of recurrence, and borderline tumors of the ovary were not
      efficiently differentiated from benign or malignant tumors by resistance index
      values obtained from color Doppler ultrasound.

PMID- 8990774
TI  - Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue:
      clinicopathologic analysis of 19 cases.
AB  - Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue type
      (MALToma) is a recently recognized disease entity. We report the
      clinicopathologic features of 19 patients with MALToma in Taiwan. The 19 patients
      included eight men and 11 women, ranging in age from 26 to 77 years, with a mean
      age of 58.8 years. Most complained of abdominal pain or gastrointestinal
      bleeding. The endoscopic and gross features of the gastric lesions revealed
      erosion (flat type), ulceration (depressed type), cobblestone appearance or
      abnormal gastric folds (elevated type), mimicking chronic gastritis, ulcer or
      early gastric carcinoma. Typical histopathologic features included
      lymphoepithelial lesion and extensive mucosal infiltration of centrocyte-like
      cells in all cases. Clonality analysis of the variable-diversity-joining region
      of the immunoglobulin gene by semi-nested polymerase chain reaction demonstrated
      monoclonality in 72% of the cases. Helicobacter pylori bacilli (H. pylori) could
      be identified on histologic sections in 15 cases (78.9%); the serologic test for
      H. pylori was positive in 12 of 13 patients tested (92%). In six patients
      receiving triple therapy (amoxicillin, bismuth subcitrate and metronidazole),
      five showed significant histologic regression with eradication of H. pylori 4 to
      6 months after the start of treatment; one patient showed persistent lesions and
      presence of H. pylori. However, persistence of residual lymphoid cells and
      monoclonality of the immunoglobulin gene, could still be demonstrated in four
      cases. Of nine patients treated with surgery or chemotherapy, two died: one due
      to concomitant gastric carcinoma and the other one due to sudden apnea. No
      recurrence was observed in the remaining seven patients. The remaining four
      patients were lost to follow-up. Our experience confirmed that gastric MALToma is
      a low-grade neoplastic process. The dramatic response of gastric MALToma to anti
      H. pylori treatment suggests that H. pylori infection is closely related to the
      pathogenesis of low-grade gastric MALToma. However, long-term follow-up is
      mandatory due to the persistence of the monoclonality of the immunoglobulin gene
      in the residual lymphoid cells after treatment.

PMID- 8990775
TI  - Clinical study of vasectomy reversal: results of 60 single-surgeon cases in
      Taiwan.
AB  - During a 10-year period, 60 men who had undergone vasectomy reversal were studied
      at Taipei Medical College Hospital. The age range of the patients was 28 to 67
      years (average, 41.9 +/- 6.9 yr). Vasectomy had been performed between 3 months
      and 35 years previously (average, 8.6 +/- 6.1 yr). The most common reason for
      requesting a vasovasostomy was the desire to have children with a new partner
      (68.3%). However, psychological symptoms (16.7%) and the desire to have a boy
      (11.7%) were also prominent findings in this study. Of 38 men who had
      postoperative semen analyses, sperm was present in the semen in 32 (84.2%), and
      pregnancy occurred in 14 of 38 couples (36.8%) within the first year of follow
      up. Repeat microsurgical reversal procedures were also promising, and of a total
      of eight patients who had repeat surgery, patency was established in five
      patients (62.5%).

PMID- 8990776
TI  - Thymic hypoplasia (DiGeorge syndrome) in a newborn with tetralogy of Fallot,
      detected by magnetic resonance imaging.
AB  - We report on a case of thymic hypoplasia (DiGeorge syndrome) associated with
      tetralogy of Fallot in a newborn. The diagnosis was established on the basis of
      echocardiography, magnetic resonance imaging (MRI) and surgical observations. In
      this paper, we emphasize that MRI may be used not only to characterize
      cardiovascular anomalies, but to diagnose thymic hypoplasia.

PMID- 8990777
TI  - Idiopathic pulmonary artery aneurysm.
AB  - The purpose of this article is to report two cases of pulmonary artery (PA)
      aneurysm in patients who had no evidence of left-to-right intracardiac shunting
      or other known relevant etiologies. One patient, a 52-year-old woman, was
      admitted to the hospital due to exertional palpitation, while the other patient,
      a 73-year-old woman, came to the hospital because of fever and cough. In both
      women, chest radiographic findings of a hugely dilated PA were confirmed by
      computed tomography (CT). In both cases, a ventriculogram showed fusiform
      dilatation of the main PA without evidence of pulmonary valve stenosis. The
      results of chest radiography, two-dimensional echocardiography, CT of the thorax,
      including pulmonary angiography in one patient, were compatible with the
      diagnosis of PA aneurysm. No specific drug regimen was administered nor was any
      surgical intervention performed in either patient. Both patients were
      asymptomatic as of the last telephone follow-up. Idiopathic PA aneurysm is a
      benign condition with better survival than PA aneurysms of other etiologies,
      because of the absence of left-to-right intracardiac shunting and significant
      pulmonary hypertension. PA aneurysm must be considered as part of the
      differential diagnosis in an enlarged pulmonary trunk seen on chest radiogram,
      and two-dimensional echocardiography should be performed initially.

PMID- 8990778
TI  - Nasopharyngeal Castleman's disease.
AB  - A 19-year-old male was admitted to our clinic because of nasal obstruction and
      intermittent postnasal drip of 3 to 4 years' duration. Physical examination
      revealed a wide-based, smooth-surfaced nasopharyngeal tumor which was suspected
      to be a nasopharyngeal angiofibroma after examination of computed tomographic
      scans and an angiogram. However, after the tumor was removed by surgical excision
      via a transpalatal approach, the pathologic examination revealed Castleman's
      disease of the hyaline-vascular type. There was neither evidence of recurrence
      nor nasal problems at 4 years' follow-up. To our knowledge, Castleman's disease,
      or angiofollicular lymph node hyperplasia, may present as a local or generalized
      tumor-like condition, usually in the chest or abdomen, and may involve both the
      lymph nodes and non-nodal tissues. A review of previous articles reveals that
      there has not been any report of Castleman's disease found in the nasopharynx.
      This rare disorder is presented and discussed.

PMID- 8990779
TI  - Delayed delivery of surviving triplet after fetal reduction and spontaneous
      abortion.
AB  - In multiple pregnancies, survival of remaining fetuses after premature death and
      delivery of one fetus is uncommon. We report a case of a triplet pregnancy that
      was reduced to twins at the 14th gestational week and then had preterm premature
      rupture of membranes and intrauterine fetal death of one twin at the 17th
      gestational week. To save the surviving fetus, delivery of the dead fetus and
      ligation of the umbilical cord at the cervical level were performed. We also
      performed McDonald cervical cerclage to keep the placenta of the dead fetus as
      well as that of the surviving one in the uterine cavity. After a series of
      aggressive procedures, including immediate administration of tocolytic agents,
      and antibiotic prophylaxis to prevent infection and preterm labor, the surviving
      fetus was delivered vaginally 73 days later due to intractable uterine
      contractions. After a 10-week hospital stay, the infant boy, weighing 2,500 g,
      was discharged without any sequelae. To our knowledge, this was the longest
      interval between deliveries in a triplet pregnancy reported in Taiwan. With
      adequate intensive management, a satisfactory outcome of the fetus and mother in
      such cases is possible.

PMID- 8990780
TI  - ECG of the month. Three Rs. Atrial flutter.

PMID- 8990781
TI  - Mycobacterial cervical lymphadenitis: a review.
AB  - Over the last decade mycobacterial infections have been shown to be on the rise
      in the United States and worldwide. The diagnosis of mycobacterial cervical
      lymphadenitis, otherwise known as scrofula, should thus be entertained when faced
      with the hallmark presentation of chronic, nontender cervical lymphadenopathy.
      This article reviews current epidemiology, bacteriology, diagnostic techniques,
      and treatment options for tuberculous and nontuberculous mycobacterial cervical
      lymphadenitis.

PMID- 8990782
TI  - Judicial action on physician-assisted suicide.

PMID- 8990783
TI  - The Journal 150 and 100 years ago. November 1846 and 1896.

PMID- 8990784
TI  - Cerebrovascular disease in the Afro-American population.
AB  - The types of stroke which are unique to Afro-American patients are reviewed. The
      major risk factors which contribute to the higher incidence of stroke in this
      population are analyzed.

PMID- 8990785
TI  - Neurosonology in clinical practice.
AB  - The role of ultrasound in the diagnosis of cerebrovascular disease is reviewed
      and is compared with other existing vascular imaging modalities. The present and
      future role of neurosonology is discussed including transcranial Doppler and
      carotid Doppler duplex ultrasound.

PMID- 8990786
TI  - Carotid endarterectomy for the asymptomatic patient.
AB  - The history of the debate on how best to manage the patient with asymptomatic
      cerebrovascular disease is reviewed. Several recent studies have compared best
      medical with surgical management. The author concludes with a perspective on the
      present and future management options.

PMID- 8990787
TI  - Anticoagulation in nonvalvular atrial fibrillation.
AB  - Atrial fibrillation is a common cardiac arrhythmia. Management of atrial
      fibrillation should focus on prevention of thromboembolic complications and the
      treatment of arrhythmia related symptoms. This article will discuss anticoagulant
      therapy in nonvalvular atrial fibrillation and review results from several
      controlled trials.

PMID- 8990788
TI  - Blood pressure management in acute stroke.
AB  - Hypertension is the major risk factor for stroke. When patients present with an
      acute stroke of ischemic or hemorrhagic type, and have elevated blood pressure,
      there is a dilemma concerning blood pressure reduction. If the blood pressure
      remains elevated, this may worsen arterial blood vessel wall injury and increase
      cerebral edema; however if blood pressure is reduced, this may reduce cerebral
      perfusion pressure and worsen neurological deficit. A review of the existing
      literature on this controversial issue is presented.

PMID- 8990789
TI  - Emergency endovascular treatment of stroke.
AB  - The key to treating arterial or venous vascular occlusive process is to remove
      the occluding thrombus. We review the available thrombolytic agents and their
      potential benefits and complications. The results of recent clinical trials are
      discussed along with strategies for treating intracranial arterial occlusion and
      venous sinus thrombosis.

PMID- 8990791
TI  - ECG of the month. Identity crisis. Ectopic atrial rhythm.

PMID- 8990790
TI  - Stroke rehabilitation: indications, outcomes, recent developments.
AB  - Following the development of fixed neurological deficit due to hemorrhagic or
      ischemic stroke, neurorehabilitation is important in the acute, subacute, and
      chronic stages to develop strategies to prevent complications and return patients
      to their maximal functional and vocational independence. This article reviews the
      potential stroke complications and strategies for effective management.

PMID- 8990792
TI  - Malignant otitis externa.
AB  - Malignant otitis externa is an uncommon but serious infection involving the
      external auditory canal, temporal bone, and surrounding soft tissue. Most
      commonly this infectious process is seen in elderly diabetics. In this article
      the pathogenesis, clinical features, diagnosis, and therapy are reviewed.

PMID- 8990793
TI  - Knee pain: a clue to internal derangement on lateral plain radiograph of the
      knee.

PMID- 8990794
TI  - The Journal 150 & 100 years ago. December 1846 and 1896.

PMID- 8990795
TI  - Refractory T cell acute lymphoblastic leukemia with unusual karyotype and
      interesting immunophenotype.
AB  - Karyotype, immunophenotype, and molecular studies are important in the evaluation
      of Acute Lymphocytic Leukemia as these data provide diagnostic as well as
      prognostic information. We present a case of acute lymphoblastic leukemia with
      unusual cytogenetics, 45,XY,i(7q),der(9)t(3;9)(q12;p22),del(12)(p12),
      :der(18)t(3;18)(p14;q22),-3. This karyotype is hypodiploid, showing loss of
      chromosome 3, a very rare occurrence. Hypodiploidy and translocations are
      suggestive of a poor clinical outcome. Cytogenetics also showed a chromosome 12p
      deletion which has been implicated in the oncogenesis of some acute leukemias.
      Immunophenotype by flow cytometry was positive for CD7 and CD10, T, and precursor
      B cell markers respectively. Given the specificity of CD7 for T cell processes,
      it was felt that the flow cytometry was more suggestive of a T cell process. Gene
      rearrangement studies showing a T cell receptor rearrangement helped confirm the
      T cell lineage of this malignancy. Hypodiploidy and T cell phenotype are
      indicators of poor prognosis. Interestingly this patient was refractory to two
      conventional chemotherapeutic protocols and finally responded to an
      unconventional protocol of high dose Ara C, etopside, and L asparaginase.

PMID- 8990797
TI  - Document management and scanning in the physician's office.
AB  - A popular PC magazine recently conducted a survey asking readers whether a
      paperless office or Santa Claus was more believable. Santa Claus won. Health care
      professionals would make that same choice. They come from an educational process
      that teaches, if it is not on paper, it never happened. However, the necessity
      for fast and easy access to medical documents, particularly in managed care
      networks, is causing the paperless office to rush forward at breakneck speed.

PMID- 8990796
TI  - The Louisiana State University Comprehensive Epilepsy Program: procedures and
      outcomes.
AB  - The first comprehensive epilepsy surgery center in Louisiana was established in
      1990 at the Louisiana State University Medical Center in New Orleans by the
      Departments of Neurology and Neurosurgery. The center performs a wide variety of
      diagnostic tests essential for the medical and surgical treatment of epilepsy
      including EEG and video monitoring, quantitative hippocampal MRI volumetry, ictal
      SPECT brain scanning, intracranial evoked potential and subdural stimulation
      functional mapping, neuropsychological evaluations, and intracarotid amobarbital
      (Wada) language and memory localization. Surgical interventions include (1) the
      placement of subdural strip and grid electrodes, depth electrodes, and foramen
      ovale electrodes, (2) temporal lobectomies, and (3) frontal, temporal, parietal,
      and occipital lobe resections. From August 1990 through October 1995 41 patients
      with medically intractable seizures underwent neurosurgical procedures for
      epilepsy. Thirty-five patients had resective surgery, while six had only
      intracranial monitoring by subdural or intracerebral electrodes. The surgical
      outcomes thus far compare favorably with those of other established centers in
      North America.

PMID- 8990798
TI  - Pheochromocytoma with elevated metanephrines as the only biochemical finding.
AB  - Pheochromocytoma is usually diagnosed by finding elevated levels of
      metanephrines, catecholamines, or vanillylmandelic acid in 24-hour urine
      collections. At least two of the three urine analytes are usually elevated. We
      found no report of a documented pheochromocytoma in which only one of the three
      analytes was elevated. Herein we report a patient with severe hypertension and a
      right adrenal mass, who was found on repeated testing to have only elevated
      urinary metanephrines. The 24-hour urine collections for vanillylmandelic acid,
      total catecholamines, fractionated catecholamines, and urine dopamine were all
      normal. The patient underwent surgery for the right adrenal mass, and the
      pathology report confirmed the diagnosis of pheochromocytoma.

PMID- 8990799
TI  - Granular cell tumor of the vulva: literature review and case report.
AB  - Granular cell tumors are an uncommon neoplasm of neural origin. They occur
      throughout the body; only about 10% are found in the vulvar region. Granular cell
      tumors are most frequent in the third and fourth decade of life, the African
      American race, and the female. Generally, they appear as small, firm, painless,
      slow-growing subcutaneous nodules. They are rarely encapsulated and recurrence is
      common. The malignant granular cell tumor is rare, representing 1% to 2% of
      cases. This form is highly aggressive, unresponsive to treatment, and ultimately
      fatal. A third type of granular cell tumor has been described which has benign
      pathologic characteristics but behaves in a clinically malignant manner. The
      treatment of choice for all types is wide, local surgical excision. A case is
      described which typifies the benign type granular cell tumor.

PMID- 8990800
TI  - The National Medical Association--an advocate for a smoke-free environment.

PMID- 8990801
TI  - Teen sex, AIDS, and contraception: Part three.

PMID- 8990802
TI  - The effects of calcium supplementation on ambulatory blood pressure in African
      American adolescents.
AB  - This longitudinal trial investigated the effects of calcium supplementation on
      the mean 24-hour blood pressure in African-American adolescents. Subjects were
      self-identified African-American adolescents from a high school in a suburb of
      Los Angeles, California. The subjects were randomly placed in a placebo or
      treatment group (placebo versus 1.5 g of calcium/day x 4 weeks). Follow-up mean
      24-hour ambulatory blood pressure (ABP) for both the treatment and control groups
      was lower than the baseline mean 24-hour ABP. In the treatment group, there was a
      decrease of 2.2 mm Hg in the mean systolic blood pressure and 0.7 mm Hg in the
      diastolic blood pressure. Relative to the placebo group, the net change in ABP
      was -1.7 mm Hg for systolic blood pressure and -0.5 mm Hg for the diastolic blood
      pressure. There was no statistically significant effect of calcium
      supplementation on the 24-hour mean ABP. The net effect of supplementation on ABP
      during waking and sleeping hours also was not significant.

PMID- 8990803
TI  - The epidemiology of homicide in Chicago.
AB  - Public health agencies across the country are beginning to view violence as a
      problem that demands a public health response. However, before such a response
      can be mounted effectively, there must be a sound data-based understanding of
      this epidemic. With this in mind, the Chicago Department of Public Health
      implemented an epidemiological analysis of homicide in the city. Using vital
      records, police data, and census data, we found that the city's homicide rate in
      1993 was 31 per 100,000 population. This rate placed Chicago 14th among other
      large cities in the United States and 4th out of the eight cities with a
      population > 1 million. The homicide rate in the city has been increasing over
      the past 30 years, but not steadily. For some intervals, the homicide rate has
      remained almost constant. African Americans, Hispanics, the young, and males are
      overrepresented in the epidemic. While guns accounted for almost 75% of all
      homicides in Chicago in 1993, gangs accounted for only 15%. Homicide cannot be
      viewed in isolation from the context of society. The literature suggests that
      poverty and racism are important risk factors for this epidemic. Although we
      cannot wait until these risk factors are remedied to develop violence prevention
      interventions, we also cannot proceed effectively without understanding this
      context.

PMID- 8990804
TI  - Serum beta-carotene deficiency in HIV-infected children.
AB  - Representative levels of serum micronutrients specifically, beta-carotene and
      vitamins A and E, were studied in symptomatic human immunodeficiency virus (HIV)
      infected children. The nutritional status of 23 symptomatic African-American and
      Hispanic HIV-infected children were compared with an appropriate control group
      comprised of 36 uninfected children matched for age and sex, using body mass
      index. Serum beta-carotene and vitamin A and E levels were randomly determined on
      15 of the infected children. Beta-carotene concentration was 4.9-fold reduced in
      symptomatic HIV-infected children when compared with the control group. There was
      a 6.5-fold decrease in the serum level for children without acquired
      immunodeficiency syndrome (AIDS) and a 13-fold reduction in children with AIDS.
      No differences in the mean values for serum vitamins A and E were observed in the
      groups studied. Although the nutritional status of the symptomatic HIV-infected
      children was not different from that of the control population, their serum beta
      carotene levels were profoundly deficient. This finding may have immunologic and
      clinical implications for children with rapidly progressing HIV disease.

PMID- 8990805
TI  - Laboratory findings in hypertensive disorders of pregnancy.
AB  - This study sought to determine whether a normal platelet count is a reliable
      predictor of the absence of other coagulation abnormalities in patients with a
      hypertensive disorder of pregnancy. A retrospective review of laboratory data
      obtained from 80 patients with hypertensive disorders of pregnancy was carried
      out. Results of complete blood cell count, prothrombin time (PT), partial
      thromboplastin time (PTT), D-dimer, fibrin split products, and fibrinogen,
      bilirubin, and liver enzyme levels were reviewed. Minor abnormalities of PT, PTT,
      and fibrinogen level were frequent, even in the presence of a normal platelet
      count. These were found mostly in patients with severe pre-eclampsia. A baseline
      complete blood cell count including platelet count is probably sufficient in
      patients with a hypertensive disorder of pregnancy. Fibrinogen level and PT and
      PTT determinations are recommended in patients who have severe preeclampsia and
      for whom operative delivery or regional anesthesia is planned. This will detect
      minor abnormalities in a few patients despite a normal platelet count. This
      information may help prevent bleeding complications.

PMID- 8990807
TI  - Characteristics of molar pregnancy in a 12 year old.
AB  - Gestational trophoblastic disease rarely is reported in early teens. This article
      describes a 12-year-old black female with molar disease, in which the
      characteristics and treatment are not dissimilar from adults.

PMID- 8990806
TI  - Nicotine dependence and depression among methadone maintenance patients.
AB  - There recently has been increasing interest at substance abuse treatment centers
      in smoking cessation treatment. Because a history of depression has been shown in
      other populations to complicate cessation efforts, the relationship between
      depression and nicotine dependence was tested in 726 methadone patients. Elevated
      odds of nicotine dependence given depression were found with three of four
      depression measures. Additional research is recommended to determine whether
      smoking cessation treatment will be more successful for methadone patients with a
      history of depression if it also addresses depression.

PMID- 8990808
TI  - Glaucoma blindness in African Americans: have 55 years of therapies,
      technologies, and talent altered blindness rates?

PMID- 8990809
TI  - [Bacterial culture of the anterior chest skin for prophylaxis in cardiovascular
      operations: prospective study in two civilian hospitals].
AB  - Mediastinitis after median stermotomy is a significant complication for a
      cardiovascular surgery. Prospective study of bacterial cultures of the anterior
      chest skin in cardiac and aortic surgery was performed with the comparison of two
      civilian hospitals. There were many ABPC-resistant bacteria including 26 to 67
      percent of Staphylococcus epidermidis (SE). ABPC could not be chosen for the
      first drug of prophylaxis. Although there was a few CEZ-resistant SE, the
      efficacy of first-generation cephalosporins was acceptable in this series. If
      methicillin-resistant Staphylococcus aureus (MRSA) is detected in patient's
      preoperative bacterial cultures, vancomycin should be selected for prophylaxis.
      In patients with poor risk who required emergent cardiac surgery, combinational
      use of an first-generation cephalosporin and an amikacin or a minocycline should
      be recommended in our data.

PMID- 8990810
TI  - [CT-guided localization for thoracoscopic pulmonary wedge resection].
AB  - Recently the identification of small-sized peripheral lung lesions has rapidly
      increased due to advancements in roentgenology. But for smaller lesions,
      definitive diagnoses by means of transbronchial or percutaneous biopsy have
      become more difficult. So we must resort to thoractomic or thoracoscopic biopsy.
      However, for thoracoscopic surgery palpation is inadequate, so the identification
      of deep or small lesions is difficult. Thoracotomy seems to be too invasive when
      used only for examination and not for therapy. Therefore, we tried CT-guided
      localization for thoracoscopic pulmonary wedge resection. Thus far we have
      performed CT-guided localization in 24 cases. Immediately prior to thoracoscopic
      surgery we placed marking devices in or beside the lesions after percutaneous
      puncture. As marking devices we used Kopans spring hook wire or a Naruke point
      marker. Pathological diagnoses of these lesions indicated 13 primary lung cancers
      (11 adenocarcinomas, 1 carcinoid, 1 squamous cell carcinoma), 4 focal fibroses, 2
      metastases of renal cell carcinoma, 1 hamartoma, 1 tuberculoma, 1 cryptococcosis,
      1 interstitial pneumonia, and 1 subpleural lymph node. The tumor diameters at
      their greatest dimension ranged from 3 to 33 mm (9.0 +/- 6.6 mm). The distance
      from the viceral pleura to the tumor surface ranged from 0 to 24 mm (10.9 +/- 6.7
      mm). In one case pneumothorax occurred due to the shallow position of the tumor
      and the loss of the marking device. If these problems (pneumothorax, bleeding,
      loss of marking devices and others) are prevented, CT-guided localization should
      be performed as soon as possible before surgery. The identification of small
      peripheral lesions can almost be determined by CT now, so such identification may
      be the most reliable technique to employ during surgery.

PMID- 8990811
TI  - [Bronchogenic carcinoma located in the aortic window].
AB  - In the patients with invasion to the aortic window, we performed operation via
      median sternotomy combined with anteroaxillar thoracotomy. In such patients with
      T4 invasion, conventional pneumonectomy could not be performed because of the
      extensive invasion near the main pulmonary artery trunk. In these patients in
      this study, complete resection of the involved pulmonary artery could be
      performed using a vascular clamp without CP bypass. Operative technique was as
      follows: first, the pericardium was opened and taping of the aorta was applied.
      When the uninvolved part of the intrapericardial pulmonary artery was long enough
      to cut, we could use a stapling device, but the stapling device could not be used
      in many cases because the length of the uninvolved segment was too short to cut
      the left pulmonary artery. In order to carry out complete resection, it was
      necessary to clamp the central part of the main pulmonary artery diagonally from
      the left lower side to the right upper side. The pulmonary arterial stump was
      closed with continuous 4-0 monofilament mattress and over and over suture. We
      recommend an aggressive surgical approach for the tumor with invasion to the
      aortic window, because the prognosis is dismal in nonresected locally advanced
      lung cancer.

PMID- 8990812
TI  - [Aortic valve regurgitation due to quadricuspid valve: a report of complicated
      case].
AB  - A 66-year-old male with the congestive heart failure was diagnosed grade 4 aortic
      valve regurgitation due to quadricuspid valve associated with bacterial
      endocarditis, widely patent left coronary artery ostium, chronic renal failure,
      and secondary hyperparathyroidism. Coronary arteriography showed that the size of
      left coronary ostium was widely patent 10 mm in diameter, and trans-esophageal
      echo cardiogram revealed perforation and vegetations on the coronary cusps of the
      aortic valve.

PMID- 8990813
TI  - [Surgical treatment of malignant hemangioendothelioma originated from the right
      atrium: a case report].
AB  - A 32-year-old man was admitted to our hospital because a cardiac tumor had been
      pointed out by a physician. CT scans showed a mass lesion with irregular patterns
      in the right atrium. The patient had the diagnosis of a malignant cardiac or
      pericardial tumor and an operation was performed. The mass originated from the
      right atrium included massive coagulated blood, and was resected with the
      pericardium and the right pleura. The histological diagnosis was malignant
      hemangioendothelioma. We present this case because only 35 patients with cardiac
      malignant hemangioendothelioma were reported in Japan.

PMID- 8990814
TI  - [Calcified EPTFE vascular prosthesis in the Blalock-Taussig shunt after 4 years
      of implantation: a case report].
AB  - A boy was born with asplenia, complete endocardial cushion defect, pulmonary
      atresia and transposition of great vessels. Modified Blalock-Taussig (BT) shunt
      procedure to the right pulmonary artery was performed using an expanded
      polytetrafluoroethylene (EPTFE) vascular graft three days after born in 1990. At
      one year old, left BT-shunt procedure was also performed. At four years old
      (1994), bi-directional Glenn procedure was performed. At that time, a piece of
      the EPTFE graft in the BT-shunt at the pulmonary anastomosis, was removed and
      observed macroscopically and microscopically. It was patent with a neointima and
      thrombi. Microscopically, multiple calcified legions and many macrophages were
      found in the graft wall. Thrombi on the graft lumen, which were suspected to be
      formed different occasions, were observed. A thin neointima with an endothelial
      cell layer near the anastomosis was remarkable. To our knowledge, this is the
      first report of such calcified lesions in the EPTFE vascular graft wall within 4
      years in the BT-shunt position in an infant.

PMID- 8990815
TI  - [A case of tricuspid valve endocarditis in a non-addicted adult person without
      underlying cardiac disease].
AB  - A very rare case of tricuspid valve endocarditis which developed in a healthy
      adult was observed. An 18-year-old man with no history of heart disease nor use
      of stimulant drugs was diagnosed as having cardiac tumor, introduced to this
      hospital and admitted. Before the operation, symptoms characteristic to infective
      endocarditis such as high fever and embolism were not observed, but the tumor was
      detected in the right ventricle by echocardiography. The patient underwent
      cardiotomy. The thrombus was removed and annuloplasty was performed by Kay's
      method, and good results were obtained. Pathologically the disease was diagnosed
      as infective endocarditis accompanied by thrombus. The postoperative course has
      been good. When the injury of the valve is slight, the surgical method preserving
      patient's own valve such as excision of localized vegetation and annuloplasty
      appears to be useful.

PMID- 8990816
TI  - [A case of acute mediastinitis with pyothorax secondary to peritonsillar
      abscess].
AB  - A 41-year-old man was admitted to a hospital elsewhere because of tonsillitis
      with high grade fever. On the 9th day of hospitalization, the patient complained
      of dysphagia and dyspnea. A chest X-ray film and a CT scan showed right pleural
      effusion and pericardial effusion, and he was referred to our hospital.
      Immediately after admission, he underwent pericardiotomy to relieve cardiac
      tamponade, and a right thoracic tube was inserted for pyothorax. Next day,
      mediastinal drainage was accomplished through a cervical incision and a right
      thoracotomy. Eight drainage tubes were left in place. Cultures revealed alpha
      Streptococcus, Neisseria and group F Streptococci. Continuous closed irrigation
      with diluted Isodine (povidone iodine) solution was performed. The last
      extubation of the drainage tube was done on the 140th day after operation. He was
      cured and discharged on the 162nd day after operation. In patients with extensive
      acute mediastinitis secondary to deep cervical infection, early complete
      mediastinal drainage via a cervical and a transthoracic incision is essential.

PMID- 8990817
TI  - [Thoracoscopic surgery for pneumothorax with bullous emphysema in an elderly
      patient: a case report].
AB  - Recent advances in optical and endoscopic operating instruments have made
      thoracoscopic surgery easier. The authors report the case of an 83-year-old
      patient who was referred to our hospital for right spontaneous pneumothorax
      associated with severe bullous emphysema. Chest X-ray films showed 40% collapse
      of right lung and the right spontaneous pneumothorax was treated by chest tube
      drainage for 3 weeks. However air leak was not decreased and subcutaneous
      emphysema appeared. Chest computerized tomography revealed multiple bullae.
      Thoracoscopic surgery was performed because of preservation of the respiratory
      function. The ruptured bulla was resected by using ENDO GIA and the other
      multiple bullae were resected similarly in order to improve the pulmonary
      function. A surgical drain was removed on the 14th postoperative day because of a
      little air leak continuing. His postoperative course was uneventful after removal
      of the chest drain. He was discharged on 27th postoperative day and had no
      shortness of breath in daily life. From our experience, thoracoscopic surgery
      appears to be much better than thoracotomy for spontaneous pneumothorax because
      of much less postoperative disability and preservation of respiratory function.

PMID- 8990818
TI  - Advocate development in the field of developmental disabilities: a data-based
      conceptual model.
AB  - We proposed a taxonomy of advocate development in the field of developmental
      disabilities derived from the systematic evaluation of a Partners in Policymaking
      program. Three developmental stages evolved: beginner, involved, and activist.
      Self-reports of advocacy actions and outcomes were collected from 3 participants
      with disabilities and 21 parents before and during training. A follow-up, semi
      structured telephone interview was conducted 5 months after training ended.
      Results indicate significant improvements in the number of actions and outcomes
      reported by all participants. The activist group had the largest gains in actions
      and outcomes; they reported twice as many outcomes as did the other participants.
      The implications of the proposed taxonomy for participants' recruitment in
      advocacy training programs were discussed.

PMID- 8990819
TI  - Advocacy in disability policy: parents and consumers as advocates.
AB  - Advocacy for change, which stems from commitment and vision, should be a
      collaborative process among parents and consumers in partnership with
      professionals. Using surveys, interactive focus groups, and telephone interviews,
      we explored the concept and activities of advocacy experienced by parents and
      individuals with disabilities. Participants were identified through an advocacy
      and leadership training program, Partners in Policymaking. Advocacy activities
      and supports and barriers to successful advocacy both for parents and consumers
      were identified. Suggestions for further research and action were proposed.

PMID- 8990820
TI  - Substituting traditional antipsychotics with risperidone for individuals with
      mental retardation.
AB  - The use of risperidone for 10 individuals with mental retardation and mental
      health disturbances was reported. A case study approach was employed to delineate
      the course of substitution of more traditional antipsychotic medications with
      risperidone. At the conclusion of the study, 6 of the 10 individuals had
      completed the substitution protocol. All participants evidenced improvement or
      resolution in side effects attributed to previous antipsychotic medication, with
      no worsening in psychiatric or behavioral status.

PMID- 8990821
TI  - Attitudes of community-living staff members toward persons with mental
      retardation, mental illness, and dual diagnosis.
AB  - Attitudes of 340 staff members in 120 community living programs for people with
      mental retardation, mental illness, and dual diagnosis and a comparison sample of
      152 community members were assessed using the Community Living Attitudes Scale, a
      measure of attitudes toward inclusion. Results showed that community agency
      supervisory and managerial staff held more favorable attitudes toward community
      living philosophy. Community support staff who worked with people who have mental
      retardation saw that population as less similar to other people than did the
      comparison sample and were less likely to endorse exclusion of persons with
      mental retardation than were those in the comparison sample. Retrospective
      analyses showed that training in inclusion philosophy was related to more
      inclusive, empowering attitudes among staff members.

PMID- 8990822
TI  - Concurrent validity study of the Slosson Intelligence Test-Revised in mental
      retardation testing.
AB  - The new Slosson Intelligence Test-Revised and the recommended abbreviated battery
      of the Stanford-Binet Intelligence Scale: Fourth Edition were given to
      individuals whose Stanford-Binet IQs ranged from 36 to 110. The Slosson-R
      correlated highly with the Stanford-Binet, r = .92. However, except for the
      moderately retarded category, the Slosson-R unsatisfactorily matched the Stanford
      Binet's assignment of individuals to IQ categories. In contrast, when all
      individuals were classified as either having or not having mental retardation,
      the match rate was much better. The Slosson-R can adequately screen for mental
      retardation, but its ability to accurately assign individuals to specific IQ
      categories appears to be limited.

PMID- 8990823
TI  - Presidential address 1996--are we there yet?

PMID- 8990824
TI  - History, the torch that illuminates: lessons from military medicine.
AB  - As in civilian medical practice, only by recording and analyzing military medical
      experiences can we apply the lessons of the past to future medical practice and
      improve the care of military personnel. Had certain problems in World War I been
      recognized and addressed, their repetition in World War II could have been
      avoided. The end of hostilities brings such a sense of relief that we are
      inclined to want to put the experience behind us. But we must remain prepared for
      any natural emergency, and one way to do that is to study the past and
      incorporate its lessons in future actions.

PMID- 8990825
TI  - Salient personality characteristics among Navy divers.
AB  - This study evaluated the personality characteristics of U.S. Navy divers. Seventy
      two active duty Navy divers completed the Million Index of Personality Styles.
      The sample strongly showed the traits of Enhancing. Modifying, Individuating,
      Thinking, and Controlling. The results are discussed in terms of adaptation to
      the environmental demands of military diving. Suggestions for further research
      are offered.

PMID- 8990826
TI  - Eye injuries during training exercises with paint balls.
AB  - The use of paint balls, increasingly popular for war games and survival games,
      has recently been introduced for certain military training exercises. We treated
      two soldiers who had severe permanent ocular damage after being hit by these
      balls. Both removed their goggles after their vision was obscured with paint from
      a hit on these protective lenses. They were then hit for a second time, resulting
      in the eye injury. Based on these cases and on a literature review, we conclude
      that protective eye gear should be mandatory when paint pellets are used. It is
      essential that service members participating in such exercises be instructed not
      to remove their protective goggles under any circumstances.

PMID- 8990827
TI  - The Army dietitian in Panama: military hospital feeding and humanitarian efforts
      during Operation Just Cause.
AB  - The delivery of nutrition during a military conflict creates added demands on
      food service operations. Dietitians in the United States Army assisted the
      civilian population in Panama by participating in humanitarian feeding efforts
      during Operation Just Cause from December 1989 to January 1990. They provided
      hospital nutrition under combat conditions and assisted in a displaced-persons
      camp by developing an Emergency Food Plan that incorporated indigenous foods. The
      Army Medical Specialist Corps instituted training programs to prepare Army
      dietitians for refugee feeding in the post-Cold War era as a result of the
      lessons learned during this and other humanitarian efforts.

PMID- 8990828
TI  - The reengineering of Naval Hospital Charleston.
AB  - Current changes in the practice of medicine and the downsizing of the military
      have resulted in the necessity to look at alternatives to current military
      hospital structure. Based on business case analysis and other economic factors,
      Naval Hospital Charleston has undergone a reorganization and introduced a primary
      care-based health care system. This model provides efficient, high-quality health
      care and addresses the need to maintain adequate support for operational forces.

PMID- 8990829
TI  - The enemy within: diarrheal rates among British and Australian troops in Iraq.
AB  - British and Australian medical teams working in Northern Iraq in 1991 providing
      primary care to refugees and the war wounded were subjected to a descriptive
      retrospective survey, 5 weeks after arriving in Iraq. The aim was to document
      different rates of diarrhea in British and Australian troops. The British, who
      were not taking daily doxycycline and did not enforce a plate- and hand-washing
      routine, experienced higher rates of diarrhea (69% of British troops compared
      with 36% of Australian troops), which was more severe and of a longer duration (p
      < 0.001) and resulted in twice as many days being lost (p < 0.001) in spite of
      the British team being half the size of the Australian contingent, and the region
      having enteropathogens with a high rate of antibiotic resistance. Vigorous hand-
      and plate-washing routines along with doxycycline prophylaxis appear to
      significantly reduce incapacitation from diarrhea in this military setting and
      have an important implication for operational effectiveness.

PMID- 8990830
TI  - Metabolic parameters that predict response to clomiphene citrate in obese oligo
      ovulatory women.
AB  - OBJECTIVE: To determine whether the presence of insulin resistance in obese
      subjects would adversely affect the rate of ovulation induction by clomiphene
      citrate. RESULTS: Fasting hyperinsulinemia was associated with the failure to
      ovulate in response to clomiphene. In addition, other parameters found to
      correlate with insulin resistance and clomiphene citrate non-response were
      elevations of total and free testosterone and lower serum sex hormone-binding
      globulin. CONCLUSIONS: The existence of the presence of endocrine abnormalities
      associated with hyperinsulinemia and insulin resistance may serve as clinical
      indicators to help predict which obese patients are likely to respond to
      clomiphene citrate therapy.

PMID- 8990831
TI  - Treatment of comminuted subtrochanteric femoral fractures in a young population
      with a reconstruction nail.
AB  - The authors report their experience using the Russell-Taylor reconstruction
      intramedullary interlocking nail in five comminuted subtrochanteric fractures in
      young paratroopers. The retrospective case series presented demonstrates the
      usefulness of this device for a challenging problem. Follow-up averaged 22 months
      and clinical results were good in that all soldiers could return to parachuting.
      The authors discuss surgical techniques and review the literature. The authors
      recommend consideration of the reconstruction nail use for this clinical problem.

PMID- 8990832
TI  - Obesity and the occurrence of heat disorders.
AB  - Obesity is often associated with poor heat tolerance. This case-control study was
      to determine the effect of obesity measured by the Body Mass Index (BMI) on the
      occurrence of heat disorders. The subjects, 218 soldiers with heat disorders and
      537 controls, were matched for age and sex. Obesity was defined as a BMI of
      greater than 27. The odds ratio for obese soldiers was 3.53; however, their
      rectal temperatures were not significantly higher at presentation for heat
      disorder. The Physical Employment Standard (PES) classifies soldiers into A, B,
      C, and E depending on medical history at the time of enlistment. Soldiers with
      PES status of A and B were at a marginally higher risk of heat disorders.
      Correcting for the effect of the PES status, the odds ratio for obese soldiers
      was 4.29. Therefore, obese soldiers training in a hot and humid environment are
      at an increased risk of heat disorders.

PMID- 8990833
TI  - Factors influencing dental utilization by U.S. military recruits.
AB  - This study identifies factors that influence dental utilization by U.S. military
      recruits prior to entering military service. Data were collected between February
      and June 1994 at one recruit in-processing site per service using self
      administered questionnaires. A prestratified, systematic, random sample of 2,711
      Army, Air Force, Navy, and Marine recruits was drawn. Women and minorities were
      oversampled. Using logistic regression to determine what factors contribute to
      the likelihood of recruits having seen a dentist over the past year reveals that
      the likelihood is greater for females, singles, Air Force personnel, Native
      Americans, and the better educated; the likelihood is less for recruits who are
      black, above 19 years old, from the Midwest, Southwest, or Pacific regions of the
      U.S., and who perceive a need for dental care. Education is the strongest
      predictor of dental utilization prior to entering military service.

PMID- 8990834
TI  - Thermoelectric technique to precisely control hyperthermic exposures of human
      whole blood.
AB  - The need in military research to avoid exposing humans to harsh environments and
      reduce animal use requires the development of in vitro models for the study of
      hyperthermic injury. A thermoelectric module (TEM) system was employed to heat
      human whole blood (HWB) in a manner similar to that experienced by heat-stroked
      rats. This system precisely and accurately replicated mild, moderate, and extreme
      heat-stress exposures. Temperature changes could be monitored without the
      introduction of a test sample thermistor, which reduced contamination problems.
      HWB with hematocrits of 45 or 50% had similar heating curves, indicating that the
      system compensated for differences in sample character. The unit's size permitted
      its containment within a standard carbon dioxide incubator to further control
      sample environment. These results indicate that the TEM system can precisely
      control temperature change in this heat stress in vitro model employing HWB.
      Information obtained from such a model could contribute to military preparedness.

PMID- 8990836
TI  - Integration of chiropractic in the Armed Forces health care system.
AB  - Congress has approved the commissioning of chiropractors in the various medical
      branches of the armed services. Currently, the Department of Defense is
      conducting a 3-year demonstration program at 10 military sites in which
      chiropractors are hired on a contractual basis to treat military personnel. This
      paper presents a brief history of chiropractic and a discussion of a major court
      case involving the AMA and other professional medical associations. A survey of
      legal, professional, and organizational issues that must be resolved prior to, or
      in conjunction with, the full integration of chiropractic in the armed services
      health care delivery system (if directed by Congress) is included. Prompted by
      the identified issues, recommended policies and actions are offered to ensure
      that this alternative health care service is effectively utilized by patient
      beneficiaries.

PMID- 8990835
TI  - Energy expenditure variations in soldiers performing military activities under
      cold and hot climate conditions.
AB  - This study assessed the energetic status of soldiers exposed to intense physical
      activities in cold and warm weather. Thirty subjects participated in a two-phase
      study group A (n = 18) in the winter phase and group B (n = 12) in the summer
      phase. Energy expenditure (EE) was measured by the doubly labeled water
      technique; after a single, oral dosing of 2H(2)18O, daily urine samples were
      collected for 12 successive days. Energy intake (EI) was assessed from detailed
      food records analyzed by computerized food charts. Energy balance was calculated
      as the difference between EI and EE for each subject. Mean (+/- SE) daily EE was
      4,281 +/- 170 and 3,937 +/- 159 kcal/day for the winter and summer groups,
      respectively. Daily EI was 2,792 +/- 124 kcal/day in group A and almost identical
      in group B. A negative energy balance of 1,422 +/- 163 kcal/day and 924 +/- 232
      kcal/day (not significant) was calculated for groups A and B, respectively.
      Energy expenditure is primarily determined by the level of activity rather than
      by climate conditions; EI is insufficient to offset the high energy requirements
      under these conditions.

PMID- 8990837
TI  - The anti-personnel land mine epidemic: a case report and review of the
      literature.
AB  - This is a review of the literature concerning the epidemiology and natural
      history of land mine deaths and injuries among civilian as well as military
      populations. Included is a case report involving the wounding and treatment of a
      member of the Croatian armed forces who stepped on and detonated a 100-g PMA-II
      anti-personnel plastic land mine. The explosive properties of PMA II is
      described.

PMID- 8990838
TI  - A combined clinical approach to treating and understanding prolonged combat
      stress reaction.
AB  - Over the last decade combat stress reaction (CSR) has received increasing
      attention in Israel and abroad. The treatment of prolonged CSR is known to be
      complicated and unrewarding, and the majority of cases became chronic. The
      authors describe the difficulties of diagnosing delayed and prolonged CSR and
      present a model of combined treatment approach through a case study.

PMID- 8990839
TI  - Exertional collapse and sudden death associated with sickle cell trait.
AB  - The most serious complication of sickle cell trait (SCT) is sudden death during
      exertion. SCT often remains unrecognized in the 2.5 million African Americans
      affected. Exertional collapse and sudden death associated with SCT is
      characterized by rhabdomyolysis, heat stroke, and cardiac arrhythmia. There is a
      40-fold increased risk of sudden death in affected soldiers during military basic
      training and there are many cases reported in athletes during preseason training.
      There have been no cases reported in soldiers beyond basic training. In the case
      presented, a soldier with 3 years of military service succumbed to SCT-associated
      sudden death during physical fitness testing.

PMID- 8990840
TI  - On science and the soul.

PMID- 8990841
TI  - Hats off to Dr. Struve's ideas for approaching unwanted pregnancy.

PMID- 8990842
TI  - Physicians should relinquish reproductive control to patients.

PMID- 8990843
TI  - Physicians should respect and support their patients' decisions.

PMID- 8990844
TI  - Healing body and spirit.

PMID- 8990845
TI  - A call for open mindedness.

PMID- 8990846
TI  - The healing power of spirituality.

PMID- 8990847
TI  - The care and cost of snowmobile-related injuries.
AB  - From January 1, 1991, through May 1, 1993, we identified 42 patients from our
      prospective computer-based trauma registry (38 males, four females; mean age, 25
      years) who were hospitalized after snowmobile accidents. The primary reason for
      hospitalization varied: bone fracture (n = 18), blunt abdominal trauma (n =
      nine), closed head injury (n = five), and miscellaneous injuries (n = 10). The
      mean injury Severity Score was 9.3 (range, one to 43; median, nine). Twenty-six
      patients (62%) required emergent operation. Mean hospital stay was six days
      (range, one to 16 days). Thirteen patients had complications: seven had wound
      infection; three, ileus; and three, miscellaneous. One severely injured
      hypothermic patient died. Medical charges totaled $569,566 (mean, $16,227; range,
      $1,003 to $51,642). Snowmobiling causes significant accidental injury in young
      persons. The physical and financial costs of such injuries are high.

PMID- 8990848
TI  - Life expectancy, life span, and the limits of medicine.

PMID- 8990849
TI  - A need for options.

PMID- 8990850
TI  - "Times are changin'".

PMID- 8990851
TI  - Radiology quiz #9. Acute epiglottitis.

PMID- 8990852
TI  - The citizen attorney general and Medicare fraud.

PMID- 8990853
TI  - Pension simplification?

PMID- 8990854
TI  - Collaborative practice arrangements require careful forethought.

PMID- 8990855
TI  - The benefits of a paperless medical practice.

PMID- 8990856
TI  - Health care development as a maturing industry, Part II.

PMID- 8990857
TI  - "Danger on the information superhighway".

PMID- 8990858
TI  - Radiology quiz #10. Osteochondral fracture of femur.

PMID- 8990859
TI  - Computers in the medical practice.
AB  - This article is part of a series covering the ever-expanding role of computers in
      the medical office and practice by Glenn L. Gordon, MD, FACIP. Dr. Gordon is
      Director, Center for Digestive and Liver Diseases, Clinical Instructor of
      Medicine at St. Louis University School of Medicine, President of Audrain County
      Medical Society, Immediate Past President of American Cancer Society-Audrain
      Unit, and State Council MSIM/ASIM Delegate. This is the first of a series of
      articles covering the expanding role of computers in our medical practice from
      office management programs to the Internet. This month's article covers the
      computerized medical record and what it can do for you.

PMID- 8990860
TI  - The influence of PCP prophylaxis on bacteriuria incidence and resistance
      development to trimethoprim/sulfamethoxazole in HIV-infected patients.
AB  - BACKGROUND: Earlier studies have shown that men infected with HIV-1 and a CD4+
      cell count below 200 mm3 are at increased risk for bacteriuria. We studied the
      effect of 3 Pneumocystis carinii (PCP) prophylaxis regimens (low-dose TMP/SMZ,
      high-dose TMP/SMZ and pentamidine aerosol) on the incidence of bacteriuria and
      resistance development to TMP/SMZ. METHODS: Retrospective analysis of 103 HIV
      positive patients. RESULTS: Nine patients using pentamidine had a positive
      culture (32%), compared to 9 patients using low-dose TMP/SMZ (17%) and 5 patients
      using high-dose TMP/SMZ (22%). These differences were not significant (P =
      0.207). However, almost all episodes in patients using TMP/SMZ were due to
      infection with a resistant strain. CONCLUSION: PCP prophylaxis with
      trimethoprim/sulfamethoxazole does not significantly influence the rate of
      bacteriuria, probably due to the development of resistance.

PMID- 8990861
TI  - Tamoxifen, balancing risks and benefits.

PMID- 8990862
TI  - Coeliac disease clinically manifest after vagotomy and oesophagectomy.
AB  - The clinical onset of coeliac disease may be precipitated by upper digestive
      tract surgery. A 66-year-old woman with asymptomatic coeliac disease that became
      clinically evident after oesophagectomy and vagotomy is presented. The surgery
      was performed for a squamous carcinoma of the hypopharynx. There had been no
      signs or symptoms of coeliac disease preoperatively. Persistent untreatable
      hypocalcaemia after the operation suggested the diagnosis. The role of surgery in
      unmasking asymptomatic coeliac disease is discussed.

PMID- 8990863
TI  - Acute hepatic injury after discontinuation of chemotherapy in a patient with non
      Hodgkin's lymphoma and chronic hepatitis B virus infection.
AB  - We describe a HBsAg-positive patient with non-Hodgkin's lymphoma who underwent
      aggressive chemotherapy. After discontinuation of chemotherapy, he developed
      jaundice due to a reactivation of the hepatitis B. Serum HBeAg and HBV DNA turned
      positive, indicating active virus replication. Abdominal CT-scan showed a large
      solitary tumour mass in the liver and the serum alpha-fetoprotein level was
      extremely high, suggesting HBV-related hepatoma. After discontinuation of
      chemotherapy, the patient died of non-Hodgkin's lymphoma and hepatocellular
      carcinoma. Throughout treatment of HBsAg-positive patients with cytotoxic or
      immunosuppressive therapy, careful monitoring of serum aminotransferase levels
      and HBV DNA is essential. Aggressive chemotherapy may have to be discontinued or
      changed to a milder regimen if hepatitis occurs.

PMID- 8990864
TI  - Liver cirrhosis due to methotrexate in a patient with rheumatoid arthritis.
AB  - A 49-year-old female with rheumatoid arthritis developed liver cirrhosis after a
      cumulative dosage of 6 g methotrexate (MTX). There were mild liver enzyme
      abnormalities, decreased liver synthesis function and possible signs of portal
      hypertension. After stopping MTX all laboratory abnormalities disappeared except
      for a mild thrombocytopenia. Risk factors and guidelines for monitoring liver
      toxicity during MTX treatment in rheumatoid arthritis are discussed.

PMID- 8990865
TI  - Leptin.
AB  - A highly conserved protein called 'leptin' was recently discovered to play a role
      in regulation of the energy balance in humans and rodents. This 167-amino-acid
      containing protein is only produced and secreted by mature adipocytes. Absence of
      the protein in mutant ob/ob mice and resistance to its effects in db/db mice lead
      to extreme obesity and type II diabetes mellitus. No mutation of the ob-gene
      encoding for leptin has been found in obese humans so far. ob mRNA in adipocytes
      and serum leptin levels are positively related to adipose tissue mass. Receptors
      for leptin have been found in the choroid plexus and hypothalamus. A feedback
      inhibition of leptin on hypothalamic neuropeptide Y (NY) production is
      postulated, as hypothalamic NY concentrations are increased in ob/ob mice and NY
      induces food intake, insulin secretion and autonomic nervous system activity.
      Insulin increases triglyceride stores in fat cells and could thereby stimulate
      leptin secretion. The ultimate intracellular pathway within the adipocyte that
      stimulates or shuts off ob mRNA expression and consequent leptin production and
      secretion remains to be elucidated. Whether leptin will ever come to play a role
      in the treatment of human obesity remains an unanswered question at the present
      time.

PMID- 8990866
TI  - An overview of managed behavioral health care.

PMID- 8990867
TI  - Managing the whole system of care.

PMID- 8990868
TI  - Creating incentives for the delivery of services.

PMID- 8990869
TI  - Public managed care: the role of the consultant.
AB  - Consultants will be increasingly important as public systems retool to fund and
      monitor managed behavioral health care services. Medicaid agencies, heretofore
      limited primarily to paying claims, must now develop expertise in RFP preparation
      and managing contracts.

PMID- 8990870
TI  - The Massachusetts Medicaid carve-out: managing care in the public sector.

PMID- 8990871
TI  - Advocacy and managed behavioral health care.

PMID- 8990872
TI  - Managed care and the next generation of mental health law.

PMID- 8990874
TI  - That's an herb, Herb.

PMID- 8990873
TI  - The public sector-private sector interface: current issues, future trends.
AB  - The public and private sectors will both be forced to change as they forge new
      relationships in order to manage the Medicaid benefit. These changes will affect
      both their organizational cultures and their technical capabilities.

PMID- 8990875
TI  - Person of the year: Commissioner Len Fishman. Interview by Bill Berlin.

PMID- 8990876
TI  - Taking care of business ... in the home.

PMID- 8990877
TI  - Is video-assisted thoracic surgery cost effective?

PMID- 8990878
TI  - Nathan Davis and medicine's move from trade to profession.

PMID- 8990879
TI  - Homegrown program promotes health in New Jersey.

PMID- 8990880
TI  - Assessing health care quality using HEDIS 3.0.

PMID- 8990881
TI  - Are we promoting too many allied health professionals instead of physicians?

PMID- 8990882
TI  - The "new" Board of Medical Examiners.

PMID- 8990883
TI  - [Mid-term results in coronary revascularization using the right gastroepiploic
      artery graft].
AB  - We studied the mid-term results in 191 patients (including emergent operation in
      27 patients) who have performed coronary artery bypass grafting (CABG) using the
      right gastroepiploic artery (REGA) for 74 months (mean follow up period was 37
      months). We evaluated the postoperative results in terms of 1. mortality and
      survival rate, 2. graft angiography, 3. cardiac event free rate and 4. abdominal
      complications. We had operative death in 6 patients (3.1%) including 3 patients
      of emergent operations. Late deaths were found in 11 patients (5.9%): 2 patients
      were cardiac death and 9 were non-cardiac. The actual survival rates were 94.2%
      at one year, 90.0% at three years and 85.9% at five years. Early patency rate of
      the RGEA was 98.9% (n = 178). However flow competition between the RGEA and
      native coronary artery was seen in 42 patients (24.0%). Mid-term patency rate was
      96.4% (n = 28). According to mid-term graft angiography, 1 patient improved and 5
      patients got worse in comparison with early control. Cardiac event free rates
      were 98.2% at 1 year, 94.8% at 3 years and 92.7% at 5 years. Abdominal
      complications were observed in 5 patients (1 patient of bleeding from the RGEA, 1
      of gastric perforation, 2 of bleeding from gastric ulcer and 1 of pyloric
      stenosis) at early period and in 7 patients (2 patients of incisional hernia and
      5 of gastric cancer) at long-term period. Early and mid-term results of CABG
      using the RGEA were quite good. However, the RGEA had a tendency of flow
      competition against native coronary artery and a problem of gastric cancer after
      the operation.

PMID- 8990884
TI  - [Management of postoperative pulmonary hypertensive crisis in children-
      indication and usefulness of inhaled nitric oxide therapy as a pulmonary
      vasodilator].
AB  - Among 176 pediatric patients who underwent open heart surgery from 1990 to 1996,
      7 developed severe pulmonary hypertensive crisis (PHC) postoperatively. All
      patients were treated with conventional medical therapy consisting of
      hyperventilation and deep sedation. Prostaglandin E1 and/or amrinone were
      administered initially as a pulmonary vasodilator, and in 3 of the 7 patients
      this resulted in immediate improvement in hemodynamics. These patients
      subsequently weaned off ventilatory support and they were discharged from the
      hospital. In 4 other patients, pulmonary vasodilator therapy with prostaglandin
      E1 and amrinone had failed and they were treated with inhaled nitric oxide (NO).
      In all patients, inhalation of NO resulted in immediate decrease in pulmonary
      pressure without significant change in systemic arterial pressure. Two patients
      successfully weaned from the ventilator, whereas in 2 patients decrease in
      pulmonary pressure was transient. They developed airway bleeding and died as a
      result of respiratory insufficiency. Although inhaled NO effectively reduced
      pulmonary pressure in patients with PHC, this effect was not maintained over 12
      hours in patients associated with bronchopulmonary dysplasia. In patients at risk
      for severe PHC, rapid treatment with NO inhalation after initial event as well as
      the prevention of lung injury caused by mechanical ventilation were found to be
      important in the postoperative management.

PMID- 8990885
TI  - [Injury to ascending aorta by cross-clamp--histologic evaluation].
AB  - To evaluate the injury to ascending aorta by cross-clamp, the trauma to the
      vessel wall was examined microscopically and the occlusive intensity of the
      vascular clamp was measured. Six patients were underwent total replacement of the
      ascending aorta and the aortic arch for aortic dissection. The ascending aorta
      and the aortic arch were resected during operation, the clamped regions of the
      ascending aorta were cut into the four pieces (the distal site, two part of the
      medial site, the proximal site applied by the vascular clamp) after operation.
      The four pieces of the ascending aorta were examined microscopically. The
      occlusive intensity of the vascular clamp were measured at the distal site, the
      medial site, and the proximal site by the load-measuring scale. The trauma to the
      vessel wall were classified to three degrees (grade 1 to grade 3). Grade 1 showed
      the minimal changes--narrowing of interstices between collagen fibers and muscle
      fibers in the media. Grade 2 showed the moderate changes--decrease of collagen
      fibers, atrophy and disruption of smooth muscle and elastic fiber in the media.
      Grade 3 showed the severe changes--disruption of the intima and defluvium of
      endothelial cells. The occlusive intensity of the vascular clamp were 1.0 kg at
      the distal site, 1.9 kg at the medial site and 3.6 kg at the proximal site,
      respectively. In the microscopic examinations, grade 1 changes were most frequent
      at the distal site, grade 1 and grade 2 changes were observed equally at the
      medial site, grade 3 change was observed only at the proximal site. The degree of
      the trauma to the vessel wall becomes severer in proportion to increase of the
      occlusive intensity of the vascular clamp.

PMID- 8990886
TI  - [Cerebral oxygen desaturation during rewarming in retrograde cerebral perfusion
      with total circulatory arrest].
AB  - To evaluate cerebral oxygen desaturation during retrograde cerebral perfusion
      with total circulatory arrest (RCP), we measured cerebral oxygen extraction (O2
      Ext), and arterio-venous oxygen differences (AV DO2) during and after RCP and
      compared the results with usual cardiopulmonary bypass (CPB) using continuous
      jugular blood saturation (SjO2) monitoring. In the RCP group, 7 patients
      underwent aortic arch replacement with RCP and in the CPB group, 4 patients
      underwent valvular surgery with CPB. A 5.5 Fr oximetric catheter was placed in
      the jugular bulb and cerebral venous and radial arterial blood were sampled.
      Oxygen partial pressure and saturation were measured at six intervals from
      cerebral venous and radial arterial blood. Measurements were taken at the
      following phases: phase I: before ECC was established, phase II: immediately
      after ECC started; phase III: at hypothermia (18 degrees C in the RCP group and
      28 degrees C in the CPB group), phase IV: during rewarming (30 degrees C), phase
      V: after rewarming (36 degrees C), phase IV: immediately after weaning from ECC.
      All 11 patients survived without neurological complications. The minimum SjO2 of
      continuous monitoring during rewarming in the RCP group was significantly lower
      than in the CPB group. AVDO2 in the RCP group was also significantly higher than
      in the CPB group during rewarming. O2 Ext in the RCP group was significantly
      higher than in the CPB group during and after rewarming. Differences in glucose
      utilization during and after rewarming were also detected. Moreover, to determine
      factors that influence SjO2 during and after rewarming, we evaluated correlations
      with arterial PaCO2, arterial pH, and rewarming duration. There were significant
      (p < 0.05) correlations between SjO2 and PaCO2 in phase IV and phase V, between
      SjO2 and pH, and between SjO2 and rewarming duration. In conclusion, continuous
      SjO2 measurements reflected cerebral oxygen desaturation during and after
      rewarming in RCP. In RCP, significantly greater desaturation during and after
      rewarming was detected than in CPB. Therefore we suggest that relatively slow
      rewarming, higher PaCO2, and more acidic pH strategies were advantageous for
      preventing desaturation during and after rewarming in RCP.

PMID- 8990887
TI  - [A case of congenital tricuspid regurgitation associated with atrial septal
      defect and peripheral pulmonary stenosis].
AB  - This report describes a 5-year-old girl with congenital tricuspid regurgitation
      associated with an atrial septal defect and peripheral pulmonary stenosis. The
      girl was diagnosed with the heart murmur at birth and recently developed the
      cardiomegaly. Cardiac echocardiography and catheterization showed severe
      tricuspid regurgitation, an atrial septal defect of the secundum type and
      peripheral pulmonary stenosis. In the operative findings, the tricuspid annulus
      was dilated to 33 mm in diameter, and leaflets were attached normally to the
      antomic annulus. There was a large cleft of the anterior leaflet of the tricuspid
      valve. Suture of the cleft and annuloplasty of the tricuspid valve, suture
      closure of the atrial septal defect and patch dilatation of peripheral pulmonary
      stenosis were successfully performed. Including this case, 19 other cases with
      congenital tricuspid regurgitation undergoing surgery were reported to date.

PMID- 8990888
TI  - [A case of coronary perforation after directional coronary atherectomy].
AB  - Directional coronary atherectomy was performed on a 69-year-old female with
      angina pectoris. She suffered from coronary perforation as a result of cardiac
      tamponade and shock. Pericardial drainage and hemostasis were performed
      immediately using a perfusion catheter. The patient was transferred to the
      operating room for perforation repair and coronary artery bypass grafting to the
      distal portion of the left anterior descending artery. The procedure was
      performed successfully. Although acute coronary perforation associated with
      directional coronary atherectomy is rare, it can be managed temporarily by a
      perfusion catheter and we successfully performed coronary artery bypass grafting.

PMID- 8990889
TI  - [Traumatic injuries of the thoracic aorta--report of five cases].
AB  - Five cases of traumatic aneurysm of the thoracic aorta associated with blunt
      chest trauma are described. Although we lost one case, four cases were
      successfully treated. Case 1, This was a 22-year-old female who underwent surgery
      for graft replacement of the descending thoracic aorta under extracorporeal
      circulation two days after injury. Case 2, This was a 17-year-old male who
      underwent surgery for graft replacement of the descending thoracic aorta under
      extracorporeal circulation 24 hours after injury. Case 3, This was a 56-year-old
      female who underwent surgery for graft replacement of the descending thoracic
      aorta under extracorporeal circulation 24 hours after injury. Case 4, This was a
      69-year-old male who underwent surgery for graft replacement with three branches
      for an aortic arch aneurysm under extracorporeal circulation one month after
      injury. Despite an emergency operation, we lost case 5 (a 21-year-old male)
      because of a complete discontinuity of the aortic isthmus. The postoperative
      course of the other four cases was uneventful. Vessel injury may be more
      widespread than preoperative radiographic findings demonstrates. Blunt chest
      trauma is usually accompanied by multisystem injury. Therefore, it is imperative
      to determine the first priority of treatment based on further preoperative
      examination in cases having associated injuries.

PMID- 8990890
TI  - [Anatomic correction of double-outlet right ventricle associated with hereditary
      spherocytosis--a case report].
AB  - A 3-year-old boy with hereditary spherocytosis (HS) underwent anatomical
      correction for double-outlet right ventricle. In addition to acute injury to the
      red blood cells during cardiopulmonary bypass, chronic mechanical trauma related
      to the presence of internal conduit and transannular patch must be considered in
      this patient with HS. We therefore performed splencetomy prior to cardiac surgery
      to prevent perioperative serious hemolysis. Preoperative examination showed the
      anatomy was considered suitable for REV procedure. The position of the aorta was
      anterior, VSD was classified as subpulmonic and associated with subvalvular
      stenosis. Under cardiopulmonary bypass, infundibular septum was resected and
      intraventricular tunnel was constructed. The pulmonary artery was transected at
      the level of the valve commissures and translocated onto the right ventricle
      without transection of aorta. Right ventricular outflow tract was reconstructed
      with a patch bearing monocusp. No serious complication due to hemolysis occurred
      perioperatively. Postoperative angiocardiography revealed no stenosis in both
      left and right ventricular outflow tract. The patient was discharged on the 57th
      postoperative day and is doing well.

PMID- 8990891
TI  - [A case of total arch graft replacement for distal aortic arch aneurysm developed
      around the site of graft patch aortoplasty].
AB  - A 65-year-old male underwent graft patch aortoplasty for a sacciform aneurysm of
      the distal aortic arch. Three years later an aneurysm developed around the site
      of the graft patch aortoplasty, therefore total arch graft replacement was
      required. The operation was performed through median sternotomy and left
      supraclavicular incision. The ascending aorta was selected for the aortic
      perfusion site, avoiding thromboembolism. Selective cerebral perfusion (SCP) was
      employed to protect the brain. Open distal anastomosis with circulatory arrest
      offered the optimal operating field despite re-operation. Graft replacement or
      graft patch aortoplasty has been proposed for the treatment of sacciform
      aneurysm. However, there is a possibility of aneurysmal change around the site of
      resected aneurysm. Furthermore because of the development of surgical skill and
      extracorporeal circulation technique, total arch graft replacement should be
      considered for the surgical treatment of distal aortic arch aneurysm.

PMID- 8990892
TI  - [Two cases of a solitary fibrous tumor with different growth patterns].
AB  - We report two cases of a solitary fibrous tumor demonstrating different growth
      patterns. Case 1: a 46-year-old male presented with a pedunculated solid tumor
      which was found between the lobes projecting from the lingula lobe. Case 2: a 68
      year-old female demonstrated a tumor, measuring 2 cm in size, clearly inside the
      lung. The tumor was covered with pleura and could be removed bluntly.
      Histopathologically, spindle shaped fibroblasts were uniformly distributed in
      abundant, tangled collagen fibers in both cases. Sinusoid-like lumens, lined with
      one endothelium layer were also found. Immunohistological staining was strongly
      positive for vimentin and CD34, while it was negative for keratin, cytokeratin
      and EMA. The diagnosis of a pedunculated solitary fibrous tumor which extruded to
      outside the lung was made in one case, while in the other case a solitary fibrous
      tumor proliferating inside the lung was diagnosed. Many investigators have
      suggested this type of tumor to derive from mesenchymal tissue under mesothelium
      cells and is thus probably different from diffuse mesothelioma.

PMID- 8990893
TI  - [A case report of an infundibular ventricular septal defect with severe right
      ventricular outflow tract obstruction due to aneurysm of the aortic sinus of
      valsalva].
AB  - This paper describes the case of a 46-year-old female. Upon contacting infective
      endocarditis at the age of 39 years, she was diagnosed with a ventricular septal
      defect (VSD). Because dyspnea gradually worsened, she was later hospitalized.
      Cardiac catheterization was performed and angiograms were taken, revealing an
      infundibular VSD accompanied by severe right ventricular outflow tract
      obstruction (RVOTO) due to aneurysm of aortic sinus of valsalva and to mild
      aortic regurgitation caused by prolapsing aortic valve. The operative procedure
      consisted of the closure of the aortic sinus fistula by continuous suture after
      excision of the aneurysmal sac and patch closure of the VSD without treatment of
      the prolapsing aortic valve. After the operation, RVOTO improved and aortic
      regurgitation disappeared. The patient was discharged and has since been well.

PMID- 8990894
TI  - [A case of adult chest wall rhabdomyosarcoma].
AB  - A 68-year-old woman was admitted to our hospital with a left anterior chest wall
      tumor. A percutaneous needle biopsy was performed, leading to a pathological
      diagnosis of pleomorphic rhabdomyosarcoma. A wide en bloc excision of the left
      anterior chest wall was performed, including the left sixth and seventh ribs. The
      defect of the chest wall was closed with Marlex mesh. Postoperative adjuvant
      chemotherapy (CYVADIC) was administered. The patient remained free of local
      recurrence two years after surgery. We conclude that wide en block excision and
      close follow-up are important in the management of rhabdomyosarcoma of the chest
      wall because of a high risk of recurrence.

PMID- 8990895
TI  - [A case of primary anterior mediastinal liposarcoma with a heterotopic mass in
      the pericardium of the same histology].
AB  - We experienced a case of primary anterior mediastinal liposarcoma with a
      heterotopic mass in the pericardium of same histology. Twenty reported cases in
      Japan were also studied. The patient was a 50-year-old male who visited the
      hospital because of an abnormal shadow on a chest X-ray. The diagnosis of
      anterior mediastinal tumor was confirmed by a chest CT. The patient underwent a
      complete resection of the mediastinal and intrapericardial masses. The histologic
      diagnosis was a well differentiated liposarcoma of Enzinger's classification. No
      evidence of recurrence or metastasis was detected in the third postoperative
      year. Liposarcoma is rarely seen in the mediastinum. Since radiotherapy and
      chemotherapy are ineffective therapeutic modalities, surgery would be the
      treatment of choice and complete surgical resection is mandatory.

PMID- 8990896
TI  - [A case of systemic artery to pulmonary vessel fistula].
AB  - A case of systemic artery to pulmonary vessel fistula was reported in this paper.
      A 44-year-old male who complained recurrent hemoptysis was admitted to our
      hospital. The angiography revealed an abnormal vascular network in the peripheral
      part of the 3rd intercostal artery. In this study, two isolated small aneurysms
      were also recognized in the right bronchial artery. For the purpose of surgical
      resection for them, video assisted right upper lobectomy was performed.
      Pathological study on resected specimen showed an artery came from extrapleural
      space penetrated the pleura and go deeper into the lung parenchyma the artery
      joined the arteriovenenous plexus which was located just beneath the thinned wall
      of the bronchiole. It is supposed that recurrent bleeding from the plexus
      perforated the thinned bronchial wall and caused intrabronchial hemorrhage.

PMID- 8990897
TI  - [Surgical treatment for patient ductus arteriosus in an aged patient].
AB  - A successful closure of patent ductus arteriosus (PDA) in a 70-year-old women is
      described. The patient had poor pulmonary function and calcification of the
      aortic arch and the descending aorta, as well as arteriosclerosis obliterans
      bilaterally in the iliac arteries. We therefore performed trans-pulmonary artery
      direct closure of the ductus arteriosus via a median strenotomy. In surgery, we
      used a Foley balloon catheter inserted into the aorta through the ductus to
      prevent backflow. Leakage of blood from the ductus, even with use of balloon
      occlusion, required the reduction of perfusion flow to 500 ml/min and temporary
      circulatory arrest. Rectal temperature was 27 degrees C when the aorta was cross
      clamped. The ductus orifice was primarily closed with three mattress sutures with
      pledgets, and this sutured orifice was secondarily covered with a bovine
      pericardial patch. The postoperative course was satisfactory. Trans-pulmonary
      artery direct closure of the PDA using cardiopulmonary bypass is useful for aged
      patients. This patient is, as far as our knowledge, the oldest surgical report in
      Japan.

PMID- 8990898
TI  - [Self-expanding nitinol stents for treatment of tracheobronchial and esophageal
      stenosis caused by lung cancer].
AB  - A 57-year-old man was admitted because of dysphagia. Two year earlier, endoscopic
      ND-YAG laser treatment had been performed for squamous cell carcinoma of the
      tracheal carina. The esophagus was compressed and narrowed by invasion of lung
      cancer. After ballooning, under endoscopic and fluoroscopic control, a self
      expanding nitinol stent (SENS, Ultraflex, Microvasive) was implanted in the
      esophagus. Immediately after esophageal prosthesis implantation, severe dyspnea
      and stridor developed because of tumor strictures in the left main bronchus.
      Under fluoroscopic and guide-wire control, SENS (Accuflex, Microvasive) was
      implanted in the tracheobronchial tree. Dyspnea, dysphagia and stridor were
      markedly improved after placement of two nitinol stents. Highly flexible,
      knitted, self-expanding nitinol stent is made of a nickel titanium alloy.
      Although the implantation of SENS in tracheobronchial stenosis has not previously
      been reported, it should be useful for prevention of airway obstruction.

PMID- 8990899
TI  - [A case of ventricular septal defect closure in patient with cytomegalo virus
      hepatitis].
AB  - Cytomegalovirus (CMV) infection has been reported to cause serious event in
      nonimmunocompromised patients after major surgery. Particularly in active case,
      the indication of surgical intervention is a difficult issue. A 7-months-old boy
      with ventricular septaldefect (VSD) has been diagnosed with CMV hepatitis. As his
      heart failure was not controlled with medication, he underwent closure of VSD at
      9 months of age while CMV was still detected in the urine and serum by polymerase
      chain reaction method. During post operative course, he was treated with
      ganciclovir and intravenous CMV hyperimmune grobiln, and CMV in the serum became
      negative and he develops no aggravation of the CMV infection postoperatively.

PMID- 8990900
TI  - [Double primary lung cancers producing alpha-fetoprotein].
AB  - A 81-year-old male with a high serum alpha-fetoprotein (AFP) level of 2644 ng/ml
      underwent left pneumonectomy for squamous cell carcinoma in the lower lobe and
      large cell carcinoma in the upper lobe. Both tumors were classified as
      pathological T2N0M0 and stage I. The AFP level was normalized to be 19 ng/ml in
      49th postoperative day. Immunohistochemical staining using anti-AFP antibody
      demonstrated AFP granules only in the large cell carcinoma. The study of lectin
      affinity against the serum AFP revealed that the concanavalin A (Con-A) non
      reactive fraction rate was 14%, the lentil agglutinin (LCA) non-reactive and
      strongly reactive subfractions were 16.7 and 83%, respectively and P2, P4 and P5
      subfractions of the erythroaggultinating phytohemagglutinin (E-PHA) were 58.6,
      24.9 and 16.5%, respectively. According to the analysis of 21 cases reported in
      the Japanese literature including our case, the AFP did not demonstrate a common
      affinity pattern against the Con-A but the common pattern resembling
      hepatocellular carcinoma against LCA and E-PHA.

PMID- 8990901
TI  - [Rupture of the aortic arch due to bacterial aortitis--a case report of a patient
      undergoing successful surgical therapy].
AB  - A 59-year-old man came to our hospital because of hoarseness and chest pain. On
      initial examination, a chest roentgenogram showed no abnormality. Three weeks
      later, while the patient was waiting to undergo a computed tomographic (CT) scan,
      shock suddenly developed. A chest roentgenogram revealed an extremely wide
      mediastinal shadow. A CT scan revealed rupture of the aortic arch near the base
      of the left subclavian artery, although there was no aneurysm. An emergency
      operation was performed. The ruptured aortic arch was replaced with an artificial
      graft during cardiopulmonary bypass with selective cerebral perfusion. A
      diagnosis of infectious aortitis was not made until a pathologist discovered
      colonies of gram-positive cocci in the resected specimen of the aortic arch.
      Postoperatively, antibiotics were administered for only four days. The patient is
      well about two years after the operation. Infectious aortitis had a very low
      prevalence and rarely involves the thoracic aorta. However, we should be aware of
      that it may cause aortic rupture even in the absence of aneurysmal dilatation.

PMID- 8990902
TI  - [A case of report of traumatic aortic regurgitation accompanying cerebral
      embolism].
AB  - Aortic regurgitation due to nonpenetrating trauma of the chest is an extremely
      rare disease and only 12 cases have been reported in this country. We report a
      case we treated and present additional of retrospective discussions. The patient
      was a 59-year-old man who lost consciousness due to a heavy blow to the chest
      during work. He was diagnosed as having acute aortic regurgitation. A close
      examination on the 3rd day after the injury revealed cerebral embolism and heart
      failure could not be controlled by physical treatment. Surgery was performed on
      the 5th day after the injury. The aorta was incised under cardiopulmonary bypass
      to examine aortic valves. Commissures between the RCC and the NCC and between the
      NCC and the LCC had been torn from the aortic wall and injured and thrombus
      adhesion was observed in a part of the NCC. After repairing the aortic wall, the
      valve was replaced by SJM valve. Postoperative course is satisfactory.

PMID- 8990903
TI  - The biological clock: it's all in the genes.

PMID- 8990904
TI  - The genetic and molecular dissection of a prototypic circadian system.
AB  - A great deal is known about this archetypal circadian system, and it is likely
      that Neurospora will represent the first circadian system in which it will be
      possible to provide a complete description of the flow of information from the
      photoreceptor, through the components of oscillator, out to a terminal aspect of
      regulation. In Neurospora the strongest case has been made for there being a
      state variable of clock identified (Hall, 1995), it has now been shown that light
      resetting of the clock is mediated by the rapid light induction of the gene
      encoding this state variable, and a number of defined clock-regulated output
      genes have been identified, in two of which the clock-specific parts of the
      promoters have been localized. In addition to the importance of these factoids
      themselves, our efforts towards understanding of this system has allowed the
      development of tools and paradigms (e.g. Loros et al., 1989; Loros and Dunlap,
      1991; Aronson et al., 1994a) that will help to pave the way for proving the
      identity of clock components in more complex systems, for understanding how
      clocks are regulated by entraining factors, and for showing how time information
      eventually is used to regulate the behaviors of clock cells, and of whole
      organisms.

PMID- 8990905
TI  - The Drosophila genes timeless and period collaborate to promote cycles of gene
      expression composing a circadian pacemaker.

PMID- 8990906
TI  - Excitatory and inhibitory amino acids and synaptic transmission in the
      suprachiasmatic nucleus.

PMID- 8990907
TI  - Astrocytes in the mammalian circadian clock: putative roles.

PMID- 8990908
TI  - Circadian rhythms of neuropeptides in the suprachiasmatic nucleus.

PMID- 8990909
TI  - Circadian rhythm generation, expression and entrainment in a molluscan model
      system.
AB  - The Bulla ocular pacemaker provides remarkable opportunities for cellular study
      of circadian pacemaker systems. The demonstration of circadian oscillations
      within individual neurons maintained in culture provides us with a first occasion
      to study the biophysical and biochemical properties of bona fide neuronal
      circadian pacemakers. The ocular clock is robust and shares formal similarity
      with other circadian systems. The development of molecular techniques that can be
      applied to single neurons should allow research on the Bulla retina to continue
      to progress towards a molecular analysis of circadian timekeeping.

PMID- 8990910
TI  - Entrainment pathways and the functional organization of the circadian system.

PMID- 8990911
TI  - Regulation of entrainment pathways by the suprachiasmatic circadian clock:
      sensitivities to second messengers.

PMID- 8990912
TI  - Light entrainment and activation of signal transduction pathways in the SCN.

PMID- 8990913
TI  - Entrainment of the circadian clock.

PMID- 8990914
TI  - Light entrainment of the mammalian biological clock.

PMID- 8990915
TI  - Regulation and integration in the mammalian circadian system.

PMID- 8990916
TI  - The role of melatonin and light in the human circadian system.

PMID- 8990917
TI  - Perinatal development of human circadian rhythms.
AB  - The early development of circadian rhythms in primates, including man, was
      reviewed. Continuous 24-h recordings were carried out for maternal and fetal
      circadian rhythms during gestation as well as in preterm infants. Several
      propositions were made based on these new findings: 1. The fetal biological clock
      is an endogenous clock capable of generating circadian rhythms and responding to
      maternal entraining signals long before the moment of birth. 2. Through the fetal
      biological clock, maternal circadian rhythms influence the fetal overt rhythms.
      3. Maternal rhythms influence the fetus, and fetal rhythms feed back to the
      mother (via the placenta). Disruption of this fetal-maternal interaction during
      gestation leads to: a. disturbances of maternal and fetal circadian rhythms; b.
      disappearance of circadian rhythms at the time of birth; c. a gestational period
      which is either too short or too long (see also Honnebier and Swaab, 1973); d.
      delayed or impaired maturation of the circadian rhythms of the infant.

PMID- 8990918
TI  - The anatomical basis for the expression of circadian rhythms: the efferent
      projections of the suprachiasmatic nucleus.

PMID- 8990919
TI  - Electrophysiology of suprachiasmatic nucleus projections to hypothalamic
      paraventricular nucleus neurons.

PMID- 8990920
TI  - SCN output drives the autonomic nervous system: with special reference to the
      autonomic function related to the regulation of glucose metabolism.

PMID- 8990921
TI  - Rhythms of inhibitory and excitatory output from the circadian timing system as
      revealed by in vivo microdialysis.

PMID- 8990922
TI  - Circadian control of reproduction in the female rat.

PMID- 8990923
TI  - A 'clock for all seasons' in the human brain.

PMID- 8990924
TI  - Sleep regulation: relation to photoperiod, sleep duration, waking activity, and
      torpor.

PMID- 8990925
TI  - Biological rhythms in the human life cycle and their relationship to functional
      changes in the suprachiasmatic nucleus.
AB  - Biological rhythms play a prominent role in the human life cycle. The endogenous
      rhythms are entrained by the environment and have an astronomical counterpart
      which is obvious for daily, monthly, and yearly rhythms, and may possibly also be
      present in weekly rhythms. Circadian rhythms are present in, e.g. testosterone
      levels, spontaneous birth, strokes, and death from cardiovascular causes.
      Circaseptan rhythms are present in, e.g. spontaneous birth, 17-ketosteroid
      levels, myocardial infarctions, and strokes. The relationship of these rhythms
      with the suprachiasmatic nucleus (SCN) has not yet been established.
      Circatrigintan rhythms, such as the menstrual cycle, have so far not been
      associated with the SCN. Circannual rhythms are present in, e.g. mood, suicides,
      reproduction, birth weight, sleep and season of birth of psychiatric patients.
      The human SCN shows strong circadian and circannual fluctuations in the number of
      neurons expressing vasopressin. The vasopressin and VIP cell population of the
      SCN develop late, i.e. for a major part postnatally. After the age of 50 the
      amplitudes of circadian and circannual fluctuations of the vasopressin cell
      numbers are reduced whereas the number of vasopressin expressing neurons
      decreases after the age of 80 and do so even more and earlier in Alzheimer's
      disease. Sex differences are present in the shape of the vasopressin subnucleus
      of the SCN and in the vasoactive intestinal polypeptide (VIP) cell number. The
      sex differences in the SCN, the doubling of the number of vasopressin neurons in
      the SCN of homosexual men, and a variety of animal experimental observations
      indicate that the SCN is involved in sexual behavior and reproduction. The exact
      role of the SCN in these processes is subject to current research.

PMID- 8990926
TI  - The suprachiasmastic nucleus: the biological clock of all seasons.

PMID- 8990927
TI  - [Prologue--adhesion molecules].
AB  - The studies on the roles of adhesion molecules in the various diseases recently
      have been greatly extended. Here, excellent studies on adhesion molecules from
      several laboratories are demonstrated in this symposium in order to clarify the
      important roles of adhesion molecules in the various diseases and disorders and
      develop the new laboratory examination on adhesion molecules in the future
      laboratory medicine.

PMID- 8990928
TI  - [Fibronectin--synergy cell recognition site].
AB  - Fibronectin is a major and multifunctional cell adhesive extracellular matrix
      protein. Many studies have been carried out to reveal its structures and
      functions. One of the most important question was the cell adhesive structures on
      the molecule and how to associate with cell surface receptors. It was striking
      that very short amino acid sequence Arg-Gly-Asp (RGD) in the central cell binding
      domain of fibronectin was determined as minimum cell adhesive sequence. However,
      other data indicate that additional subregions besides the RGD motif are required
      for its cell adhesive activity mediated by alpha 5 beta 1 fibronectin receptor.
      This putative synergistic site, second site, was analyzed by site directed
      mutagenesis studies, homology scanning using intramolecular chimeras and epitope
      mapping using inhibitory monoclonal antibodies. Those studies cleared that the
      functional sequence, Pro-His-Ser-Arg-Asn (PHSRN), synergistically enhances the
      cell-adhesive activity of RGD motif depends on the activation state of the
      integrin.

PMID- 8990929
TI  - [CpG motif in DNA from immune complexes of SLE patients augments expression of
      intercellular adhesion molecule-1 on endothelial cells].
AB  - The sequence of 9 DNA clones obtained from DNA-anti-DNA antibody immune complexes
      (IC) in 11 SLE patients was analyzed and the possible pathogenic role of the
      circulating DNA in SLE patients was discussed. Nucleic acid length of 9 cloned
      DNAs ranged from 87 to 312 base pairs(bp), with a mean length of 177 +/- 62bp,
      which were rich in guanine (G) + cytosine(C), CpG dinucleotide and palindromic
      sequences. Oligonucleotide TTTTCAATTCGAAGATGATT which contain the CpG motif in
      hexamer palindromic sequence segments in cloned DNA augmented the expression of
      ICAM-1 on the endothelial cells detected by FACS analysis and also augmented the
      gene expression of several cytokines such as interleukin-2, interleukin-6,
      interleukin-8 and tumor necrosis factor alpha. These data suggest that DNA in IC
      of SLE patients will augment expression of ICAM-1 on endothelial cells, resulting
      in exacerbation of vasculitis.

PMID- 8990931
TI  - [Adhesion molecules and carbohydrates in cancer metastasis].
AB  - Cancer metastasis is a complex phenomenon consisting of several sequential steps:
      invasion of primary sites, entry into blood or lymphatic vessels, transport,
      lodgement, extravasation, and growth at the target sites. These steps are
      achieved by peculiar interactions between tumor cells and host tissues. We
      developed several sublines from rat ascites hepatoma AH7974 that displayed
      different substrates adhesiveness and lung metastatic potential and demonstrated
      that the expression of 62 and 56kDa laminin-like substances with alpha-galactose
      residues on tumor cell surfaces is one of the determinants associated with the
      lung-colonizing potential of these cells. So, we expanded our investigation to
      detect the metastasis/prognosis-related carbohydrate antigens in primary cancers
      of the breast, lung, stomach, and large intestine by lectin histochemistry or
      immunohistochemistry. The results showed that certain types of carbohydrate
      antigen expressions in cancer cells are profoundly related to not only the mode
      of metastatic spread and the organ distribution pattern of metastasis but also
      the prognosis of cancer patients. Lymphatic metastasis was related to the
      expression of mucin core type carbohydrates (Tn antigen and Tn-like antigens) in
      common, whereas there were no conspicuous similarities in the hematogenous
      metastasis-related carbohydrates among the cancers. The expressions of blood
      group antigens such as ABH, Lewis and MN including their precursors appeared to
      be strong prognostic indicators of these cancers, although the relation of these
      antigens to each cancer varied. These results suggest that adhesion molecules
      and/or carbohydrates are one of the determinants of cancer metastasis and
      prognosis at least in part.

PMID- 8990930
TI  - [Cell adhesion molecules on platelet].
AB  - Platelets are anucleated blood cells that play a fundamental role in the
      initiation of hemostasis. In addition to platelet adhesion to the extracellular
      matrix, aggregation or platelet-platelet interaction is a requisite event in
      hemostasis. Some glycoproteins on platelet membranes mediate adhesion platelets.
      The glycoprotein (GP) Ib/IX/V complex is important in platelet adhesion and the
      GPIIb/IIIa complex mediate platelet to platelet interaction. P-selectin is a
      member of the selectin family and is transferred from secretory granules to the
      surface of activated platelets. P-selectin may function to mediate the
      interaction between activated platelets and leucocytes. We reviewed structure,
      function, biological roles and clinical application of three platelet-associated
      adhesion molecules.

PMID- 8990932
TI  - [The roles of adhesion molecules, cytokines and chemokines in relation to
      eosinophil activation in allergic inflammation].
AB  - Several characteristics of human eosinophil heterogeneity, as well as the
      existence of eosinophil subpopulations, "normodense" and "hypodense", have been
      reported in diseases associated with hypereosinophilia. Hypodense eosinophils can
      be distinguished by the increased expression of various membrane receptors
      including IL-5 receptor (J Exp Med 172:1347) and various protein expression (J
      Immunol 142:4416). Recently, adhesion molecules, as well as eosinophils, have
      been found to play an important role in the inflammatory processes in allergic
      disease. We demonstrated here as below: 1) Characteristics of adhesion molecules
      expression on eosinophils in asthma, namely, high-intensity expression of
      adhesion molecules. 2) Induction of adhesion molecule expression by PAF and
      RANTES and in addition induction by the supernatant of mononuclear cells from
      mite-allergic asthmatic patients stimulated with mite-allergen as well as with a
      combination of the recombinant IL-3, GM-CSF, and IL-5 (Immunol Lett 42:25, 1994 &
      46:241, 1995). 3) Elevated soluble ICAM-1 in bronchial asthma (Lancet 343:1108,
      1994).

PMID- 8990933
TI  - [Cell adhesion molecules on lymphocytes and their role on signal transduction].
AB  - It has been shown that cell adhesion molecules, which mediate lymphocyte adhesion
      have an ability to provide costimulation signals in the cells. One of the
      representative adhesion molecules on T lymphocytes, b1 integrin is comprised by
      several subunits sharing a common b1 subunits, CD29, which is defined by
      monoclonal anti-4B4 antibody. We have demonstrated that b1 integrins function as
      a cell surface receptor for extracellular matrix (ECM) protein, such as collagen
      and fibronectin. We also found that fibronectin, ligand of b1 integrin,
      synergized with anti-CD3 antibody to promote proliferation of CD4 T cell in a
      serum free culture system, and also induced an independent signal which would be
      distinct from the CD3/TcR-mediated signal pathway of activation through the
      induction of an AP-1 transcription factor. Recent studies revealed that there is
      an accumulation of CD4+CD29+ T cells, memory T cells as well as prominent
      increase of a variety of inflammatory cytokines in the synovial fluid of patients
      with rheumatoid arthritis (RA). This suggests that b1 integrins may play an
      important role for the inflammatory mechanism in RA. Regulation of signal
      transduction mediated by adhesion molecules on lymphocytes may be the possible
      effective way for controlling the pathological inflammatory process in RA.

PMID- 8990934
TI  - [Clinical evaluation of immuno-serological laboratory data].
AB  - Clinical evaluations of various laboratory data from immuno-serological tests
      such as rheumatoid factor, anti-nuclear antibody, and other auto antibodies were
      reviewed. Rheumatoid factors (RF) were discussed in relation to positivity in
      various diseases, immunoglobulin class of RF, and correlation between titers of
      RF and circulating immune complex (IC). As a result, higher frequency and higher
      titers of IgA-RF were found in Sjogren syndrome patients. Titers of RF did not
      show disease activity of RA, but those of ESR and CRP did. Anti-nuclear
      antibodies (ANA) were discussed in relation to positivity in healthy subjects,
      specific antibodies and corresponding specific disease, correlation among titers
      of anti-dsDNA antibody, CH50 and circulating immune complex. As a result, an ANA
      frequency of 40% was found in healthy young women. Values of CH50 were much
      better than ANA titers for evaluating clinical activity in SLE patients. Findings
      of anti-cardiolipin antibody in thrombosis patients with connective tissue
      vascular disease (CVD), anti-centromere antibody in various CVD patients as well
      as CREST patients and primary biliary cirrhosis patients and anti-neutrophil
      cytoplasmic antibodies in various vascular diseases along with inflammatory bowel
      disease patients were presented. Finally, useful laboratory data at different
      clinical steps such as diagnosis, evaluation of disease activity and estimation
      of prognosis were demonstrated in CVD.

PMID- 8990936
TI  - [Detection of HIV-1 in plasma samples using microplate hybridization after RT
      PCR].
AB  - We have developed a microplate hybridization(MH) technique, which utilizes the
      non-isotopic method of enzyme-linked assay for detection of HIV in the amplified
      product after PCR. HIV RNA extracted from plasma was amplified by RT-Nested-PCR
      using biotinylated-inner primers of gag, pol and env regions, respectively. The
      PCR product was visualized by 5% polyacrylamide gel electrophoresis and ethidium
      bromide staining. The heat-denatured PCR product was hybridized with HIVcDNA of
      each region which was immobilized to a microplate. The hybridized microplate was
      reacted with streptavidin-conjugate peroxidase and then the optical density(O.D.)
      was read at 490nm. The cut off value was determined at O.D. 0.25. The results of
      the electrophoresis of gag, pol and env regions were all positive in 53 HIV-1
      seropositive samples from Japan and the USA, and all negative in 55 HIV-1
      seronegative samples. Using the MH technique, USA samples showed a higher O.D.
      than the Japan samples, particularly in the pol region. The results of MH
      technique in gag and pol regions coincided with that of electrophoresis. But, one
      of 27 Japanese HIV-1 seropositive samples showed O.D. of less than 0.2 in only
      env region. This particular sample was classified by V3 peptide-based enzyme
      immunoassay as subtype E, which differs from the typical subtype B of Japan and
      USA samples. This suggests the presence of several genotypes in HIV-1
      seropositive individuals in Japan. Based on this data, the MH technique using
      gag, pol and env region is a simple, sensitive, safe and specific assay for
      detection of HIV-1 RNA in plasma, and would be useful in clinical testing.

PMID- 8990937
TI  - [Detection of numerical chromosomal aberrations in hematopoietic malignancy by in
      situ hybridization on bone marrow aspirate paraffin sections].
AB  - We evaluated the usefulness of in situ hybridization (ISH) with chromosome
      specific DNA probe on paraffin sections of bone marrow aspirates. Twenty cases of
      hematopoietic malignancy and eight control cases of non-hematopoietic malignancy
      were examined with centromere-specific probes for chromosomes 8 and 17. In the
      eight control cases, the mean rates of cells with more than three hybridization
      signals were 1.13 (2SD = 1.90) for chromosome 8, and 0.88 (2SD = 2.25) for
      chromosome 17. The mean rates plus 2SD were 3.03 for chromosome 8, and 3.19 for
      chromosome 17. Therefore, we defined cases of more than 4.0% of cells showing
      more than three hybridization signals per nuclei as having a numerical
      abnormality (trisomy). We compared these results with conventional cytogenetic
      results by karyotype analysis. In twenty hematopoietic malignancy cases, three
      cases demonstrated trisomy 8 by ISH. Two cases also demonstrated this abnormality
      by karyotype analysis, but one case showed no abnormality by karyotype analysis.
      While trisomy 17 detected in one case that did not demonstrate numerical
      abnormality, only structural abnormality by karyotype analysis. The rate of
      discrepancy between results of ISH analysis and those of karyotype analysis was
      only 5% (2/40) for both chromosomes. In five cases, re-examinations were
      performed within three months. In one case, we could not obtain adequate material
      for karyotype analysis. However, this case showed trisomy 8 by ISH. Structural
      chromosomal abnormalities such as translocation or deletion could not be detected
      by this ISH analysis with centromere-specific probes. However, this method has
      the advantage result that we can perform retrospective assessments, do not need
      to culture cell, and can compare with pathological findings. Thus, we conclude
      that ISH analysis with paraffin sections of bone marrow aspirates will provide
      more useful information by combining ISH analysis and karyotype analysis.

PMID- 8990938
TI  - [Genetic diagnosis of pelvic lymph node metastasis in prostate cancer using
      aspiration biopsy samples].
AB  - We have developed a highly sensitive method to detect pelvic lymph node(LN)
      metastasis using reverse transcriptase-polymerase chain reaction(RT-PCR) with the
      primers specific for prostate-specific antigen(PSA) gene in combination with the
      fine needle aspiration biopsy(FNAB). The specimens were obtained from pelvic LN
      from 15 prostate cancer patients and 15 bladder cancer patients. The aspirated
      samples (0.05 approximately 0.1 ml) were used for detecting the fragment of PSA
      mRNA by RT-PCR and Southern blot analysis, and the rest of samples were submitted
      to conventional cytology. Expression of PSA gene was detected in 9 cases of FNAB
      samples including all 5 cytologically positive and further more 2 cytologically
      class III cases, and 2 of 8 cytologically negative cases. RT-PCR of FNAB samples
      from all cases of bladder cancer were negative for the detection of PSA gene. The
      sensitivity of PSA gene by RT-PCR was very high and could detect 10 degrees
      cancer cell. In conclusion, our study suggested that RT-PCR for detection of PSA
      gene in FNAB samples might become a new diagnostic tool for detection of small
      foci of prostatic cancer metastasis in LN and combination use of RT-PCR and
      cytology could greatly contribute to accuracy in diagnosis.

PMID- 8990939
TI  - [Usefulness of the modified Greipp's morphological classification of multiple
      myeloma cells].
AB  - In order to clarify the clinical usefulness of the morphological classification
      of multiple myeloma (MM) originally proposed by Greipp, et al. and modified by
      us, Giemsa-stained MM cells in bone marrows obtained from 61 untreated patients
      were analyzed. According to the original classification, there was no significant
      difference in survival time between the patients with plasmablastic MM and those
      with other types. However, the mean survival time of each type of MM according to
      the modified classification was 2014 days in mature MM, 1564 days in intermediate
      MM, 967 days in immature MM, and 254 days in plasmablastic MM. The survival time
      of plasmablastic MM was significantly shorter than those of other types. DNA
      aneuploidy was observed more frequently in plasmablastic MM than in other types.
      Furthermore, PCNA- and Ki-67-positive rates were higher in plasmablastic MM than
      in other ones. Four of five patients with plasmablastic MM who were treated with
      VAD(vincristine, doxorubicin, dexamethasone) regimen showed no significant
      effect, and most patients with the type died of sepsis or renal failure. From
      these results, it was concluded that patients with plasmablastic MM have a poor
      prognosis. Moreover, our modified classification is recommended as a clinically
      useful approach for selecting treatment strategy and predicting an accurate
      prognosis.

PMID- 8990941
TI  - [Increased urinary iron excretion rate in patients with non-insulin dependent
      diabetes mellitus].
AB  - Urinary iron excretion rate(u-FeER, microgram/min) in urine at night time from 58
      patients with non-insulin dependent diabetes mellitus and 8 controls was measured
      by atomic absorption. The patients were divided into three groups according to
      urinary albumin excretion rate(u-AER), namely, Group I(n = 44): less than 20
      micrograms/min of u-AER; Group II(n = 9): 20 < or = u-AER < 200 micrograms/min;
      Group III(n = 5): more than 200 micrograms/min of u-AER. The u-FeER in group
      III(56.3 +/- 14.8 ng/min, mean +/- SEM) was significantly higher than that in
      controls (4.0 +/- 1.6ng/min), group I(8.3 +/- 1.6 ng/min) and group II(18.5 +/-
      6.5ng/min). The increase of u-FeER in group III indicates that urinary iron may
      at least partly play a role in development of diabetic nephropathy.

PMID- 8990940
TI  - [In situ detection of Epstein-Barr virus in the non-neoplastic gastric glands and
      infiltrated lymphocytes].
AB  - Recently, clonal EBV-DNA and/or EBV-encoded small RNA(EBER1) have been detected
      in some gastric carcinomas. We reported the first observation of EBV infection in
      gastric glands with intestinal metaplasia, and characterized the EBV-infected
      lymphocytes which infiltrated in gastric mucosa. To determine the cellular
      location of EBV, EBER1 in situ hybridization(ISH) with an EBER1 oligonucleotide
      probe was applied to paraffin sections of the non-neoplastic gastric mucosa in 80
      cases of gastric carcinoma and 49 cases of gastric ulcer. Not only was EBER1
      expression detected in the nucleus of gastric cancer cells(5 cases) but also in
      non-neoplastic gastric epithelial cells(3 cases) and in infiltrated
      lymphocytes(40 cases). A single or a few shedding non-neoplastic epithelial cells
      in 2 cases of EBV-associated gastric cancer showed EBER1 expression. In one case,
      EBER1 was observed in all of the epithelial cells of a few gastric glands with
      intestinal metaplasia, suggesting that the stem cells of the metaplastic gastric
      glands were infected with EBV. EBV DNA was also detected in the EBER1-positive
      metaplastic glands scratched from the paraffin section by a single cell PCR
      method with a BamHI W primer pair. However, immunohistochemical examination
      showed that these metaplastic glands lacked expression of EBNA2 and LMP-1. The
      observation of these rare EBV-infected metaplastic glands reinforces the pre
      transformation EBV infection hypothesis for EBV-associated gastric carcinoma. The
      double staining using ISH and immunohistochemistry revealed that EBER1 positive
      lymphocytes showed a B cell marker of L26(< 50%) but not T cell markers of UCHL1
      and OPD4.

PMID- 8990942
TI  - [Dynamic structure change of protein secretion machinery].

PMID- 8990943
TI  - [Nuclear targeting of viral genome].

PMID- 8990944
TI  - [Wingless/Wnt signal transduction mechanism].

PMID- 8990945
TI  - [Structure and function of a cell adhesive signal, Arg-Gly-Asp sequence].

PMID- 8990947
TI  - [Fluorescent nucleotides: their applications for studies on the structure and
      function of proteins].

PMID- 8990946
TI  - [Molecular cloning of ADH7 encoding human class IV (sigma) ADH and its clinical
      significance].

PMID- 8990948
TI  - [The beginning of research and methodology on biosensor].

PMID- 8990949
TI  - [Analysis of molecular interaction by fluorescence polarization method].

PMID- 8990951
TI  - Purines '96.

PMID- 8990952
TI  - Presenilin mutations in Alzheimer's disease: molecular models suggest a potential
      functional locus.

PMID- 8990954
TI  - Pharmacokinetics of fluoxetine.

PMID- 8990953
TI  - Fluorescent ligands for the study of receptors.

PMID- 8990955
TI  - An indirect action for fluoxetine on the dopamine neurotransmitter system.

PMID- 8990956
TI  - Solving inconsistencies in the analysis of receptor-ligand interactions.
AB  - According to the occupation model, the observed sigmoidicity in receptor-binding
      studies frequently yields non-integer values for the number of molecules that
      bind per receptor, which may suggest inconsistencies of the model. Here, Bertil
      Tuk and Michael van Oostenbruggen re-examine the derivation of the model and
      pinpoint the origin of the observed inconsistencies, thereby demonstrating that
      these inconsistencies may lead to substantial error in estimates of receptor
      affinity, number of molecules that bind per receptor and cooperativity. A
      reformulated model allows more information to be derived from receptor-binding
      experiments, yielding integer estimates of the number of molecules that bind per
      receptor and quantitatively estimating the degree of cooperativity.

PMID- 8990957
TI  - The neurochemistry of morphine addiction in the neocortex.
AB  - Different strategies have been used in an attempt to understand the neurobiology
      of opioid addiction. Here, Michele Simonato initially discusses the
      identification of key anatomical areas involved in the phenomenon and purposes an
      explanation of opioid addiction based on the theory of complexity. The variable
      importance of direct and indirect effects in phenotypically different neuronal
      populations can imply differences in the adaptive changes that occur with chronic
      morphine exposure. Opioid addiction is therefore proposed as a complex
      multicellular event, where individual neurones differentially adapt both on the
      basis of the signals they receive and of their second messengers and genetic
      programmes.

PMID- 8990958
TI  - G protein-coupled receptors: heterologous regulation of homologous
      desensitization and its implications.
AB  - Two patterns of rapid desensitization have been characterized for G protein
      coupled receptors: homologous desensitization, which mainly involves G protein
      coupled receptor kinases and arrestins, and heterologous desensitization, which
      mainly involves protein kinases A (PKA) and C (PKC). In this review, Tsu Tshen
      Chuang and colleagues discuss evidence to show that PKA and PKC can modify the
      functional state of the G protein-coupled receptor kinases/arrestin homologous
      desensitization machinery, providing a novel level of cross-talk in signal
      transduction. Studies on regulation of G protein-coupled receptor kinases and
      arrestins confirm that the functional state of this machinery may have important
      consequences for cellular responsiveness and may represent new targets for
      therapeutic strategies.

PMID- 8990959
TI  - Recent advances in the pharmacology of the vestibulo-ocular reflex system.
AB  - Recent advances in the pharmacology of the vestibulo-ocular reflex have had a
      major impact on our understanding of the vestibular system, the sensory system
      primarily concerned with the stabilization of gaze and posture during head
      movement. Increasing evidence suggests that afferent transmission from the
      receptor hair cells in the vestibular labyrinth to the vestibular nerve probably
      involves glutamate acting on a number of excitatory amino acid receptor subtypes.
      Furthermore, hair-cell sensitivity appears to be regulated by cholinergic, GABA
      mediated and, possibly, peptide-mediated efferent feedback from the CNS.
      Likewise, it seems clear that an excitatory amino acid, probably glutamate, is
      the major transmitter used by the vestibular nerve in its synapses with neurones
      of the brainstem vestibular nucleus. In this review, Paul Smith and Cynthia
      Darlington discuss the large number of receptor subtypes that have been
      identified in the vestibular nucleus, including receptors for several peptides
      that may have a role in co-transmission.

PMID- 8990960
TI  - Expanded programme on immunization (EPI). Progress towards poliomyelitis
      eradication, 1990-1996.

PMID- 8990961
TI  - Health conditions for travellers to Saudi Arabia. Pilgrimage to Mecca (Hajj).

PMID- 8990962
TI  - Zoonoses control. Crimean-Congo haemorrhagic fever.

PMID- 8990963
TI  - Military women as wives and mothers.
AB  - The increasing number of women in the military, especially married women and
      mothers, is forcing the military to accommodate populations it did not have to
      deal with in the past. The military community has responded by initiating
      programs that address the needs of active duty wives and mothers, especially with
      regard to family support, health care, and available child care facilities.
      However, many policy questions pertaining to military women remain, including
      nondeployment of breastfeeding women or mothers of small infants, treating the
      family as the unit of analysis and not just the service member, and providing
      programs such as WIC and Head Start to its members overseas.

PMID- 8990964
TI  - Exercise in the prevention and treatment of chronic disorders.
AB  - The Defense Women's Health Research Initiative commissioned a review of the
      literature of women's health issues. This was performed and published by the
      Institute of Medicine. In this publication it was noted that health promotion and
      disease prevention in women should be an area of high priority for military
      medicine. This article details some of the ways in which exercise may make
      substantial contributions to this goal. The available evidence indicates that
      there is an inverse association between physical activity and a variety of
      chronic diseases. Moreover, physical activity appears to influence psychological
      well-being. Aerobic exercise is the mode most frequently studied, and appears to
      confer positive changes, but other forms of exercise may prove to be equally
      beneficial. However, the appropriate duration, intensity, and frequency of the
      exercise have not been determined for any of these chronic health problems and
      must be considered before global recommendations can be offered. Efforts to
      promote physical activity within the community, schools, and homes must be
      initiated to achieve the goals set forth in Healthy People 2000, so the health of
      our women can improve. Future studies will be required to identify mechanisms
      whereby physical activity confers benefit.

PMID- 8990965
TI  - Chronic dieting in active women: what are the health consequences?
AB  - Evidence suggests that there is ever increasing pressure on American women to be
      thin. This pressure drives women to want to be thinner than what might be
      realistically achieved or required for good health. Our goal as nutrition and
      health professionals is to help women achieve and maintain a healthy body weight
      throughout the life-cycle. This includes helping young females accept their body
      size and shape as well and placing more emphasis on health and fitness than on
      weight in this population. This process begins with the identification of what
      constitutes a healthy body weight for a particular individual based on genetic,
      physiological, social, and psychological factors. In addition, it should be a
      weight that can be realistically maintained while keeping risk factors for
      chronic disease low. Table 1 outlines some strategies for helping individuals to
      identify and maintain a healthy body weight.

PMID- 8990966
TI  - Vaginitis/cervicitis: diagnosis and treatment options in a limited resource
      environment.

PMID- 8990967
TI  - Advances in the computational study of language acquisition.
AB  - This paper provides a tutorial introduction to computational studies of how
      children learn their native languages. Its aim is to make recent advances
      accessible to the broader research community, and to place them in the context of
      current theoretical issues. The first section locates computational studies and
      behavioral studies within a common theoretical framework. The next two sections
      review two papers that appear in this volume: one on learning the meanings of
      words and one or learning the sounds of words. The following section highlights
      an idea which emerges independently in these two papers and which I have dubbed
      autonomous bootstrapping. Classical bootstrapping hypotheses propose that
      children begin to get a toc-hold in a particular linguistic domain, such as
      syntax, by exploiting information from another domain, such as semantics.
      Autonomous bootstrapping complements the cross-domain acquisition strategies of
      classical bootstrapping with strategies that apply within a single domain.
      Autonomous bootstrapping strategies work by representing partial and/or uncertain
      linguistic knowledge and using it to analyze the input. The next two sections
      review two more more contributions to this special issue: one on learning word
      meanings via selectional preferences and one on algorithms for setting
      grammatical parameters. The final section suggests directions for future
      research.

PMID- 8990968
TI  - A computational study of cross-situational techniques for learning word-to
      meaning mappings.
AB  - This paper presents a computational study of part of the lexical-acquisition task
      faced by children, namely the acquisition of word-to-meaning mappings. It first
      approximates this task as a formal mathematical problem. It then presents an
      implemented algorithm for solving this problem, illustrating its operation on a
      small example. This algorithm offers one precise interpretation of the intuitive
      notions of cross-situational learning and the principle of contrast applied
      between words in an utterance. It robustly learns a homonymous lexicon despite
      noisy multi-word input, in the presence of referential uncertainty, with no prior
      knowledge that is specific to the language being learned. Computational
      simulations demonstrate the robustness of this algorithm and illustrate how
      algorithms based on cross-situational learning and the principle of contrast
      might be able to solve lexical-acquisition problems of the size faced by
      children, under weak, worst-case assumptions about the type and quantity of data
      available.

PMID- 8990969
TI  - Distributional regularity and phonotactic constraints are useful for
      segmentation.
AB  - In order to acquire a lexicon, young children must segment speech into words,
      even though most words are unfamiliar to them. This is a non-trivial task because
      speech lacks any acoustic analog of the blank spaces between printed words. Two
      sources of information that might be useful for this task are distributional
      regularity and phonotactic constraints. Informally, distributional regularity
      refers to the intuition that sound sequences that occur frequently and in a
      variety of contexts are better candidates for the lexicon than those that occur
      rarely or in few contexts. We express that intuition formally by a class of
      functions called DR functions. We then put forth three hypotheses: First, that
      children segment using DR functions. Second, that they exploit phonotactic
      constraints on the possible pronunciations of words in their language.
      Specifically, they exploit both the requirement that every word must have a vowel
      and the constraints that languages impose on word-initial and word-final
      consonant clusters. Third, that children learn which word-boundary clusters are
      permitted in their language by assuming that all permissible word-boundary
      clusters will eventually occur at utterance boundaries. Using computational
      simulation, we investigate the effectiveness of these strategies for segmenting
      broad phonetic transcripts of child-directed English. The results show that DR
      functions and phonotactic constraints can be used to significantly improve
      segmentation. Further, the contributions of DR functions and phonotactic
      constraints are largely independent, so using both yields better segmentation
      than using either one alone. Finally, learning the permissible word-boundary
      clusters from utterance boundaries does not degrade segmentation performance.

PMID- 8990970
TI  - Selectional constraints: an information-theoretic model and its computational
      realization.
AB  - A new, information-theoretic model of selectional constraints is proposed. The
      strategy adopted here is a minimalist one: how far can one get making as few
      assumptions as possible? In keeping with that strategy, the proposed model
      consists of only two components: first, a fairly generic taxonomic representation
      of concepts, and, second, a probabilistic formalization of selectional
      constraints defined in terms of that taxonomy, computed on the basis of simple,
      observable frequencies of co-occurrence between predicates and their arguments.
      Unlike traditional selection restrictions, the information-theoretic approach
      avoids empirical problems associated with definitional theories of word meaning,
      accommodates the observation that semantic anomaly often appears to be a matter
      of degree, and provides an account of how selectional constraints can be learned.
      A computational implementation of the model "learns" selectional constraints from
      collections of naturally occurring text; the predictions of the implemented model
      are evaluated against judgments elicited from adult subjects, and used to explore
      the way that arguments are syntactically realized for a class of English verbs.
      The paper concludes with a discussion of the role of selectional constraints in
      the acquisition of verb meaning.

PMID- 8990971
TI  - A language learning model for finite parameter spaces.
AB  - This paper shows how to formally characterize language learning in a finite
      parameter space, for instance, in the principles-and-parameters approach to
      language, as a Markov structure. New language learning results follow directly;
      we can explicitly calculate how many positive examples on average ("sample
      complexity") it will take for a learner to correctly identify a target language
      with high probability. We show how sample complexity varies with input
      distributions and learning regimes. In particular we find that the average time
      to converge under reasonable language input distributions for a simple three
      parameter system first described by Gibson and Wexler (1994) is psychologically
      plausible, in the range of 100-150 positive examples. We further find that a
      simple random step algorithm-that is, simply jumping from one language hypothesis
      to another rather than changing one parameter at a time-works faster and always
      converges to the right target language, in contrast to the single-step, local
      parameter setting method advocated in some recent work.

PMID- 8990972
TI  - Modularity and development: the case of spatial reorientation.
AB  - In a series of experiments, young children who were disoriented in a novel
      environment reoriented themselves in accord with the large-scale shape of the
      environment but not in accord with nongeometric properties of the environment
      such as the color of a wall, the patterning on a box, or the categorical identity
      of an object. Because children's failure to reorient by nongeometric information
      cannot be attributed to limits on their ability to detect, remember, or use that
      information for other purposes, this failure suggests that children's
      reorientation, at least in relatively novel environments, depends on a mechanism
      that is informationally encapsulated and task-specific: two hallmarks of modular
      cognitive processes. Parallel studies with rats suggest that children share this
      mechanism with at least some adult nonhuman mammals. In contrast, our own studies
      of human adults, who readily solved our tasks by conjoining nongeometric and
      geometric information, indicated that the most striking limitations of this
      mechanism are overcome during human development. These findings support broader
      proposals concerning the domain specificity of humans' core cognitive abilities,
      the conservation of cognitive abilities across related species and over the
      course of human development, and the developmental processes by which core
      abilities are extended to permit more flexible, uniquely human kinds of problem
      solving.

PMID- 8990973
TI  - Children's use of counterfactual thinking in causal reasoning.
AB  - Research on children's causal thinking has emphasized the perception of temporal
      and spatial contiguity between cause and effect. However, our causal judgements
      often involve a contrast between a perceived sequence (A, then B) and a
      counterfactual case (in the absence of A, then not B). In three experiments,
      children's capacity for such counterfactual thinking was assessed. In Experiment
      I, children aged 3-5 years observed a sequence such as A causing B. Subsequently,
      they replied quite accurately to a question about a counterfactual sequence, for
      example: "What if A had not occurred, then B or not B?". In Experiment 2,
      children were asked about two counterfactual antecedents, one that would not have
      caused B, and one that (like the actual antecedent) would also have caused B.
      Children differentiated between the two types of antecedent. Finally, in
      Experiment 3, children heard stories in which the protagonist chose a course of
      action that led to a minor mishap (e.g., drawing with a black pen and getting
      inky fingers), having rejected an option that would have prevented it in
      experimental stories (e.g., using a pencil) or an option that would have led to
      an equivalent outcome in control stories (e.g., using a blue pen). Children aged
      3 and 4 years often cited the failure to adopt another course of action as the
      cause of the mishap and, particularly in experimental stories, they focused on
      the rejection of the alternative option. Children's use of counterfactual
      thinking is discussed in relation to contemporary accounts of causal reasoning.

PMID- 8990974
TI  - Subject-verb agreement in Spanish and English: differences in the role of
      conceptual constraints.
AB  - This paper reports studies of subject-verb agreement errors with speakers of
      Spanish and English; we used a sentence completion task, first introduced by Bock
      and Miller (1991). In a series of four experiments, we assessed the role of
      semantic information carried by the sentential subject in the induction of
      subject-verb agreement errors. For Spanish speakers, a sentence preamble such as
      la etiqueta score las botellas (the label on the bottles), which is usually
      interpreted to denote several labels, induced more agreement errors than
      preambles that normally denote a single entity. This finding replicates previous
      research with Italian (Vigliocco et al., 1995). English speakers, on the other
      hand, were not sensitive to this semantic dimension, as was found earlier by Bock
      and Miller (1991). This cross-linguistic difference is discussed in the framework
      of a modified version of the computational model of grammatical encoding proposed
      by Kempen and Hoenkamp (1987). In this version of the model agreement is computed
      through a unification operation instead of feature-copying, allowing for an
      independent retrieval of agreement features from the conceptual representation
      for the subject and the verb. We propose that languages differ in the extent to
      which the selection of the verb is controlled by features on the subject and
      features from the conceptual representation.

PMID- 8990975
TI  - Learning from a connectionist model of the acquisition of the English past tense.

PMID- 8990976
TI  - Why many concepts are metaphorical.

PMID- 8990977
TI  - Two-way conversation with a mass spectrometer: nondestructive interactive mass
      spectrometry.
AB  - Most mass spectrometers employ destructive detection, so that it is necessary to
      repeat an experiment in order to vary even one parameter. In contrast, Fourier
      transform ion cyclotron resonance mass spectrometry offers nondestructive
      detection, so that ions remain available for further manipulation and
      redetection. Here, we show for the first time how to perform mass spectrometry
      interactively. Following each elementary experimental stage, such as ion
      generation, isolation, dissociation, or detection, the operator is free to choose
      and tailor the next stage without creating a fresh supply of ions. For example,
      we can test the effect of varying one parameter over several values without
      having to repeat the entire experimental event sequence each time, much like
      varying one letter or word in a sentence without having to rewrite the whole
      sentence. Such interactive control promises to speed development of complex
      experimental event sequences, as for optimizing the sequencing and structural
      analysis of tiny amounts (e.g., femtomoles or less) of biomacromolecules
      (peptides, nucleic acids, oligosaccharides).

PMID- 8990978
TI  - Genetically engineered bacteria: electrochemical sensing systems for antimonite
      and arsenite.
AB  - A bacterial sensing system that responds selectively to antimonite and arsenite
      has been investigated. The bacteria used in these studies have been genetically
      engineered to produce the enzyme beta-galactosidase in response to these ions.
      This is accomplished by using a plasmid that incorporates the gene for beta
      galactosidase (reporter gene) under the control of the promoter of the ars
      operon. This plasmid also encodes for the ArsR protein, a regulatory protein of
      the ars operon, which, in the absence of antimonite or arsenite, restricts the
      expression of beta-galactosidase. In the presence of antimonite or arsenite the
      ArsR protein is released from the operator/ promoter region of the ars operon and
      beta-galactosidase is expressed. The activity of this enzyme was monitored
      electrochemically using p-aminophenyl beta-D-galactopyranoside as the substrate.
      The bacterial sensing system responds selectively to arsenite and antimonite (and
      to a lesser extent arsenate) and shows no significant response to phosphate,
      sulfate, nitrate, and carbonate.

PMID- 8990979
TI  - Polymer- versus silica-based separation media: elimination of nonspecific
      interactions in the chiral recognition process through functional polymer design.
AB  - A novel chiral stationary phase that contains a new chiral selector based on L
      valine-3,5-dimethylanilide attached to monodisperse poly(glycidyl methacrylate-co
      ethylene dimethacrylate) beads has been prepared. The polymeric separation medium
      provides greatly enhanced enantioselectivities and reduced retention times when
      compared to the analogous silica-based chiral stationary phase in the separation
      of the enantiomers of 3,5-dinitrobenzamido derivatives of alpha-amino acids under
      normal-phase HPLC conditions. Separation factors (alpha) of up to 7 were achieved
      with the polymeric separation medium, which is also useful for the separation of
      large samples under overload conditions.

PMID- 8990980
TI  - Synchronized scanning of the first and second mass spectrometers on tandem double
      focusing mass spectrometers.
AB  - A method is described to synchronize the scans of the first and second double
      focusing mass spectrometers of a tandem double-focusing mass spectrometer. The
      scans are synchronized by scanning the first mass spectrometer with voltages
      instead of the magnetic field. The method is demonstrated with scans that provide
      all of the precursor ions that produce a selected product ion (precursor ion
      scan). These precursor ion scans are compared to the previous method of obtaining
      precursor ion scans on a tandem double-focusing mass spectrometer. The precursor
      ion scans using the synchronized scanning allow for the use of high-energy
      collisions on any tandem double-focusing mass spectrometer, while limiting the
      mass range possible in a single scan. The limited mass range may be corrected by
      obtaining several spectra with different magnetic fields on the first mass
      spectrometer.

PMID- 8990981
TI  - Implementing the UN Convention on the Rights of the Child.

PMID- 8990982
TI  - Falling back on charity.

PMID- 8990983
TI  - What makes a just healthcare system?

PMID- 8990984
TI  - Medicine, postmodernism, and the end of certainty.

PMID- 8990985
TI  - The power of placebo.

PMID- 8990986
TI  - The magic of seven.

PMID- 8990987
TI  - How can we live forever?

PMID- 8990988
TI  - Distance is dead: the world will change.

PMID- 8990989
TI  - "I'm all right, John": voting patterns and mortality in England and Wales, 1981
      92.
AB  - OBJECTIVE: To investigate the association between voting patterns, deprivation,
      and mortality across England and Wales. DESIGN: Ecological study. SETTING: All
      the electoral constituencies of England and Wales. MAIN OUTCOME MEASURES:
      Combined and sex specific standardised mortality ratios. RESULTS: For the years
      surrounding the three elections of 1983, 1987, and 1992 overall standardised
      mortality ratios showed substantial negative correlations of -0.74 to -0.76 with
      Conservative voting and substantial positive correlations of 0.73 to 0.77 with
      Labour voting (all P < 0.0001). Correlations were higher for male than female
      mortality. Conservative voting was strongly negatively correlated (r = -0.84)
      with the Townsend deprivation score, while Labour voting was positively
      correlated (r = 0.74) with this. Labour and Conservative voting explained more of
      the variance in mortality than did the Townsend score. In multiple regression
      analyses for the 1992 election Labour voting (P < 0.0001), Conservative voting (P
      < 0.0001), the Townsend score (P = 0.016), and abstentions (P = 0.032) were all
      associated with mortality. Labour and conservative voting explained 61% of the
      variance in mortality between constituencies; when Townsend score and abstentions
      were added this increased to 63%. CONCLUSIONS: Conservative and Labour voting are
      at least as strongly associated with mortality as is a standard deprivation
      index. Voting patterns may add information above that provided by indicators of
      material deprivation. People living in better circumstances and who have better
      health, who are least likely to require unemployment benefit and free school
      meals or to rely on a state pension in old age, and who are most able to opt out
      of state subsidised provision of transport, education, and the NHS, vote for the
      party that is most likely to dismantle the welfare state.

PMID- 8990990
TI  - Attendance at cultural events, reading books or periodicals, and making music or
      singing in a choir as determinants for survival: Swedish interview survey of
      living conditions.
AB  - OBJECTIVES: To investigate the possible influence of attendance at cultural
      events, reading books or periodicals, making music or singing in a choir as
      determinants for survival. DESIGN: A simple random sample was drawn of 15,198
      individuals aged 16-74 years. Of these, 85% (12,982) were interviewed by trained
      non-medical interviewers between 1982 and 1983 about cultural activities. They
      were followed up with respect to survival until 31 December 1991. SETTING:
      Swedish interview survey of living conditions comprising a random sample of the
      adult Swedish population. SUBJECTS: 12,675 people interviewed between 1982 and
      1983. MAIN OUTCOME MEASURES: Survival of subjects after controlling for eight
      confounding variables: age, sex, education level, income, long term disease,
      social network, smoking, and physical exercise. RESULTS: 6,301 men and 6,374
      women were followed up; 533 men and 314 women died during this period. The
      control variables influenced survival in the expected directions except for
      social network for men; a significant negative effective was found when the
      analysis was made separately for men and women. We found an influence on
      mortality when the eight control variables were controlled for in people who
      rarely attended events compared with those attending most often, the relative
      risk being 1.57 (95% confidence interval 1.18 to 2.09). CONCLUSION: Attendance at
      cultural events may have a positive influence on survival. Long term follow up of
      large samples with confounders that are well controlled for and with the cultural
      stimulation more highly specified should be used to try to falsify the hypothesis
      before experiments start.

PMID- 8990991
TI  - Which doctors die first? Analysis of BMJ obituary columns.

PMID- 8990992
TI  - Freedom, responsibility, and health.
AB  - Freedom and responsibility, how much of each and how they are balanced, have
      profound implications for our personal lives and for our work. The health of a
      population and its achievement in the workplace are enhanced when individuals
      have some freedom and some responsibility, but not too much of either, and when
      civil associations of individuals rather than individuals acting alone are the
      essential social units. The consistent association of social contacts with health
      and productivity provides strong support for the premise that intimate
      relationships are the focus around which people's lives revolve. Membership of a
      "social network" may be merely conforming to a reigning social norm, and this
      could mean having to pay an important price in the loss of creativity associated
      with individualism. But social conformity should not prevent individuals from
      going their own way, and it should be possible to combine the luxury of
      individuality with an active life in civic affairs. Less than complete freedom
      may fall short of existential utopia, but it may be best for our health and
      wellbeing.

PMID- 8990993
TI  - Commentary: understanding it all--health, meta-theories, and mortality trends.

PMID- 8990994
TI  - Dances of death, occupational mortality statistics, and social critique.
AB  - In the late middle ages and early renaissance dances of death were a popular art
      form. Despite important differences in outlook, the moral messages of these art
      forms and of modern analyses of socioeconomic inequalities in mortality overlap
      considerably. This theme has survived in modern dances of death, which are
      popular in certain parts of Europe, especially in Germany and other German
      speaking countries in central Europe, and are clearly inspired by the late
      medieval and early renaissance examples. In the modern dances of death, however,
      unlike their historical counterparts, social critique (criticism of social
      inequality) is almost absent, although they include representations of
      differences between people in social position. Remarkably, references to
      socioeconomic inequalities in mortality, which have been documented extensively,
      are also uncommon in the modern examples. This raises important questions about
      public perception of social inequality in general and socioeconomic inequalities
      in mortality in particular, and it suggests that modern Western society has not
      developed the cultural means of conveying the moral message that follows from
      research into socioeconomic inequalities in health.

PMID- 8990995
TI  - Lust.

PMID- 8990996
TI  - Envy.

PMID- 8990997
TI  - Wrath.

PMID- 8990998
TI  - Pride.

PMID- 8990999
TI  - Gluttony.

PMID- 8991000
TI  - Sloth.

PMID- 8991001
TI  - Greed.

PMID- 8991002
TI  - Circaseptennial rhythm in ear growth.

PMID- 8991003
TI  - A personal therapeutic journey.

PMID- 8991004
TI  - SatelLife: getting relevant information to the developing world.

PMID- 8991005
TI  - Rights, wrongs, and journals in the age of cyberspace. "We all want to change the
      world".

PMID- 8991006
TI  - Egil's or Paget's disease?

PMID- 8991007
TI  - Promoting attachment, providing memories.

PMID- 8991008
TI  - Premature grey hair and hair loss among smokers: a new opportunity for health
      education?

PMID- 8991009
TI  - A fish induced pneumothorax: dilemmas in the remote management of a sucking chest
      wound.

PMID- 8991010
TI  - Clinically significant pulmonary barotrauma after inflation of party balloons.

PMID- 8991011
TI  - "Phlebomania Hancocksia": prevalence of a previously undescribed psychomotor
      disturbance.

PMID- 8991012
TI  - Buccaling under the pressure: influence of secondary care establishments on the
      prescribing of glyceryl trinitrate buccal tablets in primary care.
AB  - OBJECTIVE: To determine which characteristics were the best predictors of high
      rates of prescribing of glyceryl trinitrate buccal tablets. DESIGN: Practice and
      patient characteristics from 197 practices were examined, and a multiple
      regression analysis was performed to examine which variables were important in
      predicting this prescribing. SETTING: Former family health services authority
      (197 practices). MAIN OUTCOME MEASURE: Volume of prescribing of glyceryl
      trinitrate buccal tablets. RESULTS: Four variables contributed significantly to a
      multiple regression model: the catchment area of the secondary care
      establishment; the number of partners in a practice; the level of practice
      deprivation; and whether the practice served an urban or a rural area. The model
      suggests that the most important variable was the catchment area of the secondary
      care establishment in which the practice was located. CONCLUSION: Although only
      the prescribing of short acting glyceryl trinitrate buccal tablets was studied,
      an impact of this size on primary care prescribing may have extensive
      implications for all drug expenditure in primary care.

PMID- 8991014
TI  - Product names, proper claims? More ethical issues in the marketing of drugs.
AB  - OBJECTIVES: To analyse the explicit or implicit claims embodied in the
      proprietary names of pharmaceutical products. DESIGN: Linguistic and ethical
      analysis of proprietary names of pharmaceutical products marketed in the UK and
      in Denmark. RESULTS AND CONCLUSIONS: A number of drugs have names that allude to
      their indication or actions. Such names may be problematic, however, because they
      often promise more than the drug can deliver. Taking into account, firstly, the
      type of allusion and its degree of sophistication, and, secondly, the seriousness
      of the indication may help in identifying the most problematic drug names.

PMID- 8991013
TI  - Effect of colour of drugs: systematic review of perceived effect of drugs and of
      their effectiveness.
AB  - OBJECTIVE: To assess the impact of the colour of a drug's formulation on its
      perceived effect and its effectiveness and to examine whether antidepressant
      drugs available in the Netherlands are different in colour from hypnotic,
      sedative, and anxiolytic drugs. DESIGN: Systematic review of 12 published
      studies. Six studies examined the perceived action of different coloured drugs
      and six the influence of the colour of a drug on its effectiveness. The colours
      of samples of 49 drugs affecting the central nervous system were assessed using a
      colour atlas. MAIN OUTCOME MEASURES: Perceived stimulant action versus perceived
      depressant action of colour of drugs; the trials that assessed the effect of
      drugs in different colours were done in patients with different diseases and had
      different outcome measures. RESULTS: The studies on perceived action of coloured
      drugs showed that red, yellow, and orange are associated with a stimulant effect,
      while blue and green are related to a tranquillising effect. The trials that
      assessed the impact of the colour of drugs on their effectiveness showed
      inconsistent differences between colours. The quality of the methods of these
      trials was variable. Hypnotic, sedative, and anxiolytic drugs were more likely
      than antidepressants to be green, blue, or purple. CONCLUSIONS: Colours affect
      the perceived action of a drug and seem to influence the effectiveness of a drug.
      Moreover, a relation exists between the colouring of drugs that affect the
      central nervous system and the indications for which they are used. Research
      contributing to a better understanding of the effect of the colour of drugs is
      warranted.

PMID- 8991015
TI  - Narcosis and nightshade.
AB  - Although this year marks the 150th anniversary of the discovery of modern
      surgical anaesthesia, surgery itself has a much longer history. It is well known
      that extracts from the opium poppy, Papaver somniferum, were used to dull the
      pain of surgery during ancient times but less well known that extracts from
      plants with sedative powers often accompanied them, producing primitive
      anaesthesia. Most of these sedative plants were members of a large botanical
      family, the Solanaceae. This paper describes some of them and discusses the ways
      in which they were administered. It also explains why, during the middle ages,
      these primitive techniques went out of use but how none the less they provided
      Shakespeare with the inspiration for some of his greatest plays. When the active
      principal of the Solanaceae was identified as scopolamine, it came to play a part
      in 20th century anaesthesia. The combination of omnopon and scopolamine lives on
      as a premedication, and the presence of poppy heads and mandrake roots on the
      arms of today's Association of Anaesthetists serves to remind us of the
      speciality's links with its past.

PMID- 8991016
TI  - A training culture in surgery.

PMID- 8991017
TI  - To err was fatal.

PMID- 8991018
TI  - Recharging the batteries.

PMID- 8991019
TI  - Why do medical students choose St Mary's Hospital Medical School?

PMID- 8991020
TI  - Does nursing have a future?

PMID- 8991021
TI  - The truth about doctors' handwriting: a prospective study.
AB  - OBJECTIVES: To determine whether doctors have worse handwriting than other health
      professionals. DESIGN: Comparison of handwriting samples collected prospectively
      in a standardised 10 seconds' task. SETTING: Courses on quality improvement.
      SUBJECTS: 209 health care professionals attending the courses, including 82
      doctors. MAIN OUTCOME MEASURES: Legibility rated on a four-point scale by four
      raters. RESULTS: The handwriting of doctors was no less legible than that of non
      doctors. Significantly lower legibility than average was associated with being an
      executive and being male. Overall legibility scores were normally distributed,
      with median legibility equivalent to a rating between "fair" and "good."
      CONCLUSION: This study fails to support the conventional wisdom that doctors'
      handwriting is worse than others.' Illegible writing is, however, an important
      cause of waste and hazard in medical care, but efforts to improve the safety and
      efficiency of written communication must approach the problem systemically- and
      assume that the problems are in inherent in average human writing-rather than
      treating doctors as if they were a special subpopulation.

PMID- 8991022
TI  - Mizspellin and Medline.

PMID- 8991023
TI  - Introducing Selfcite 2.0--career enhancing software.

PMID- 8991024
TI  - [Endoscopic retrograde cholangiography and endosonography. Respective indications
      in case of suspicion of common bile duct calculi].
AB  - The new methods for diagnosis and treatment of biliary lithiasis, including
      laparoscopic cholecystectomy, have encouraged work into new means of searching
      for a stone in the main bile duct. The management strategy for an individual
      patient can only be determined on the basis of the clinical situation and the
      relative expectations of the different diagnostic and therapeutic methods
      available. The current strategy does not take into consideration the contribution
      of magnetic resonance cholangiography which must be evaluated in comparison with
      endosonography. In general, when operative risk is moderate or low,
      endosonography is indicated, with or without sphincterotomy. In high-risk
      patients, endoscopic retrograde cholangiography would be indicated. Of course,
      this strategy depends on the facilities available and the experience of the
      surgical team. A self-assessment procedures will help determine the most cost
      effective strategy.

PMID- 8991025
TI  - [Evaluation of an intervention on the prescription and biological surveillance of
      low-molecular weight heparins in medicine].
AB  - OBJECTIVES: We evaluated the effect of oral recommendations documents distributed
      to prescribing physicians on the use of low-molecular weight heparin (LMWH) and
      laboratory test orders. METHODS: Prescription of LMWH over a 6 month period was
      left to the total discretion of the prescribing physician (observation period).
      An information session and recommendation documents were then proposed describing
      prophylactic use of LMWH and appropriate hemostasis monitoring tests for curative
      treatments. Prescriptions and laboratory test orders were then recorded for the
      next six months (intervention period). RESULTS: Diffusion of recommendation
      documents to prescribers led to a 50% decrease in the prescription of low
      molecular weight heparin for prophylaxis and a significant drop in orders for
      anti-Xa and prothrombin. CONCLUSION: These results confirm the efficacity of
      informing prescribing physicians on the use of low-molecular weight heparins and
      underlines the need to validate methods used for the prevention of venous
      thrombosis.

PMID- 8991026
TI  - [Electric burns: epidemiological and therapeutic aspects].
AB  - OBJECTIVES: A retrospective study of patients with electrical burns was conducted
      to choose criteria for initial dispatching and establish a treatment protocol for
      out patient management. METHODS: The study included 67 patients injured by
      electrical current and admitted at Edouard Herriot Hospital Burns Unit between
      January 1st 1990 and January 1st 1993. RESULTS: Low-voltage currents (< 1000
      Volts) responsible for serious and immediate cardio-vascular diseases occurred in
      domestic accidents, mostly with children. High-voltage current (> 1000 Volts)
      responsible for deep burn injuries occurred in accidents at work and mostly with
      adults. Twenty-two were outpatients and 45 were admitted at once. Two died on
      admission, 24 were hospitalized less than five days, 11 required repeated
      surgical treatments and a long stay at hospital, and 8 were severely burned and
      were admitted to the intensive-care unit. Two required continuous venovenous
      hemodialysis for three weeks. Morbidity of the last three groups was nil,
      morbidity remained high in term of functional and aesthetic after-effects.
      CONCLUSION: Information on prevention of electrical burns should be intensified.

PMID- 8991027
TI  - [Legionnaires' disease in the Paris area: epidemiology and mortality. Apropos of
      a series of 81 culture-positive cases].
AB  - OBJECTIVES: Evaluate etiological circumstances and prognosis in Legionnaires'
      disease. METHODS: A series of 81 culture-proven cases of Legionnaires' disease
      was collected in the Paris area between 1989 and 1994. RESULTS: Direct
      immunofluorescence assay was positive for Legionella pneumophilia in 48% of the
      cases. Serogroup 1 was isolated in 88% of the cases. The median age of the
      patients was 51 years and 74% were males. Infection was nosocomial in 28% of the
      cases. Immunosuppression was present in 45% of the patients (transplantation,
      cancer, leukemia). Among the immunosuppressed patients, 7 were HIV-infected.
      Mortality due to legionellosis reached 27%. This high mortality was probably
      related to patient selection criteria. CONCLUSION: Mortality from Legionnaires'
      disease remains high as confirmed in this series.

PMID- 8991028
TI  - [Role of nitric oxide in the regulation of arterial pressure and renal function].
AB  - Nitric oxide (NO) is produced by three isoforms of NO synthase which catalyze the
      oxidation of L-arginine. Endothelial and neuronal NO synthases are constitutive
      and activated by an increase of intracellular calcium concentration. Activity of
      the inducible NO synthase is implied in inflammatory processes and does not
      depend on intracellular calcium. In the vessels, NO induces an active
      vasodilatory tone. Inhibition of NO synthases by L-arginine analogs results in a
      long-lasting pressor effect with renal damage, which demonstrates the role of the
      NO in the control of blood pressure and renal function. A defect of NO synthesis
      by endothelial or renal cells could be involved in the pathogenesis of salt
      sensitive hypertension whereas, in other forms of hypertension, vascular NO would
      have a compensatory role. In the kidney, NO regulates glomerular filtration by
      vasodilating the glomerular afferent and, to a lesser extent, efferent arterioles
      and by increasing the ultrafiltration coefficient (Kf). NO is implied in the
      relationship between renal perfusion pressure and natriuresis and alters the
      tubulo-glomerular retrocontrol. The effects of the glomerular induction of NO
      synthase are under evaluation in various models of glomerulonephritis.

PMID- 8991029
TI  - [Pancreatic cystic lesions of difficult diagnosis].
AB  - Cystic lesions of the pancreas include pseudocysts (90%), cystic tumors and true
      cysts. Preoperative diagnosis will guide the therapeutic strategy. Certain
      malignant or potentially malignant cysts (mucinous cystadenomas and
      cystadenocarcinomas) should be removed surgically while others (pseudocysts and
      serous cystadenomas) are almost always benign. In 3 out of 4 cases, the clinical
      setting guides diagnosis and with adequate imaging (sonography, computed
      tomography, endosonography) the correct diagnosis can be obtained. Inversely, the
      nature of a unique macrocyst it is often difficult to identify. Puncture is
      useful to determine tumor markers which are sometimes helpful in complementing
      information provided by imaging techniques.

PMID- 8991030
TI  - [Acute eosinophilic lung during minocycline therapy].

PMID- 8991031
TI  - [Uveitis and joint pain without pulmonary involvement disclosing Chlamydia
      pneumoniae infection].

PMID- 8991032
TI  - [Postoperative involvement of the pudendal nerve after orthopedic surgery].

PMID- 8991033
TI  - [Iatrogenic Raynaud phenomenon caused by local infiltration].

PMID- 8991034
TI  - [Causes of death in patients with medullary cancer of the thyroid. GETC. Groupe
      d'Etude des Tumeurs a Calcitonine].
AB  - OBJECTIVE: Medullary thyroid carcinoma (MTC) is characterized by different
      clinical forms and a possible prolonged survival, despite presence of metastases.
      In the present study, we have studied the clinical and biological characteristics
      of 119 decreased MTC patients. METHODS: Our data were retrieved retrospectively
      from the French medullary thyroid cancer study group (GETC). RESULTS: Our results
      showed that the cause of death was basically MTC (87%) but not exclusively,
      depending on the clinical forms and the age. Patients with type IIb multiple
      endocrine meoplasia (MEN) died earlier from their carcinoma. Patients with type
      IIa MEN died of causes other than MTC, especially pheochromocytoma. Two-thirds of
      the patients with sporadic forms of MTC, died with advanced metastases, usually
      from MTC. CONCLUSION: A significant number of deaths in patients with medullary
      thyroid carcinoma result from non-cancerous causes. This study established the
      clinical and biological characteristics of patients at risk of death.

PMID- 8991035
TI  - [Adult-onset acute rheumatic fever: 4 cases in Guadeloupe].
AB  - OBJECTIVE: Rheumatic fever has become infrequent in developed countries. Recent
      regional epidemics, particularly in North America, brought our attention to this
      disease in our area. In the French Caribbean Islands, rheumatic fever remains an
      important health problem despite much progress in the last 15 years. METHODS: A
      retrospective survey over the last 5 years identified 19 cases of rheumatic fever
      in Guadeloupe in subjects over 19 years of age. RESULTS: Among these subjects 4
      cases of rheumatic fever beginning in adulthood were analysed and compared with
      data in the literature. CONCLUSION: The diagnosis of rheumatic fever beginning in
      adulthood is difficult to establish. Joint symptoms are variable and cardiac
      involvement, which occurs in 30 to 40% of the cases, is highly suggestive. The
      kinetics of antistreptococci antibodies confirms the diagnosis.

PMID- 8991036
TI  - [Acute pituitary necrosis after multiple pituitary stimulation test].
AB  - Iatrogenic necrosis of the pituitary gland is well-known but rarely caused by
      stimulation tests used to investigate pituitary adenomas; 26 cases have been
      reported in the literature. We report 2 new cases where the chronology of the
      events suggests the sudden necrosis resulted from stimulation tests. Several
      mechanisms have been proposed. It is not possible to define increased risk as a
      function of the adenoma histology. In most cases, voluminous tumors are revealed
      by visual dysfunction. These accidents should not overshadow the role of function
      tests in neurosurgical situations. Outcome is usually favorable after acute
      necrosis.

PMID- 8991037
TI  - [Congenital heart diseases surgically treated in childhood. Long-term results].
AB  - Surgery for hereditary cardiopathies has made much progress over the last 25
      years. For left/right ventricular shunts, mortality is 5% and quality of life is
      satisfactory in 85% at five years. All interventricular communications with major
      pulmonary hypertension should be operated during the first year of life. When
      surgery is indicated for atrial left/right shunt the operation should be done
      before the age of 4 or 5 years. Results for Fallot's tetralogy are now excellent
      with an actuarial survival of more than 30 years in 86% of simple forms after
      curative surgery. Complete repair should be done early (12 to 18 months) to
      reduce dysrhythmia and right ventricular hypertrophy. Corrective atrial surgery
      for transposition of the great vessels, a totally physiological operation, has
      been replaced by anatomic correction, improving prognosis to more than 90%
      survival and only 10% reoperation rate. Surgery for coarctation of the aorta
      gives very good results modulated by the risk of recurrence, especially when
      performed early (before 6 months). Medical-surgical management of hereditary
      cardiopathies begins at birth. Surgery for all operable malformations should be
      performed before the end of the second year of life, allowing for nearly normal
      life, both at home and at school.

PMID- 8991038
TI  - [Immunological diagnosis of paraneoplastic neurologic syndromes].
AB  - Paraneoplasic neurological syndromes are defined as an association between
      neurological disease and cancer in the absence of metastatic, infectious or
      metabolic complications. These syndromes occur in less than 1% of patients with
      cancer. With the exception of the Lambert-Eaton syndrome in which an autoimmune
      mechanism has been proven, the pathogenesis of paraneoplasic neurological
      syndromes remains unknown despite a frequent association with anti-Hu, anti-Yo,
      and anti-Ri antibodies. Neither passive transfer of these antibodies nor
      immunization with recombinant proteins has been able to produce paraneoplasic
      syndromes in animal models. It is most likely that cell immunity or other
      antigenic mechanisms are also implicated and that the synthesis of anti-Hu, anti
      Yo or anti-Ri is simply one manifestation of a more complex immune reaction.
      Nevertheless, the discovery of these antibodies can be useful in the diagnosis of
      cancer, especially in the early stages. Other antibodies, specific for
      paraneoplasic neurological syndromes, will undoubtedly be discovered in the
      future, increasing the capacity of immunological diagnosis. A better
      understanding of immune cross reactions between the tumor and the nervous system
      may help further our understanding of the immune system and lead to progress in
      specific treatment for paraneoplasic neurological syndromes.

PMID- 8991039
TI  - [Hyperlipidemia in pregnancy].
AB  - Hyperlipidemia is one of the most striking modification of biological parameters
      occurring during normal pregnancy. Hypertriglyceridemia is the most prominent
      feature, with a less dramatic increase of total cholesterol levels. Besides these
      quantitative changes, most lipoproteins undergo qualitative modification
      throughout pregnancy such as triglyceride enrichment of the particles. Kinetics
      and magnitude of plasma lipids changes have been well recognized, but the
      mechanisms, metabolic fate and impact on the pathogenesis of cardiovascular
      disease are not totally unravelled. The primary modulators are estrogens, insulin
      and lipoprotein lipase. Hyperlipidemia is a result of the metabolic adaptation of
      the maternal organism to pregnancy allowing to save glucose and energy for the
      fetus, reversible within a few weeks in postpartum. However some have suggested a
      trend toward an increased risk for coronary disease after multiple pregnancies.
      In case of preexisting hyperlipidemia, whether familial or not-primary or
      secondary, pregnancy presents an additional challenge. Except from exceptional
      complications, dietary counselling will be the only treatment, under a close
      follow-up.

PMID- 8991040
TI  - [Use of Orgaran for extracorporeal circulation in a patient allergic to heparin].

PMID- 8991041
TI  - [Ectopic ending of the common bile duct in the 3rd duodenum: an anatomical
      curiosity not to be unknown].

PMID- 8991042
TI  - [Idiopathic and recurrent stupor: efficacy of flumazenil].

PMID- 8991043
TI  - [Hypereosinophilia after calcium heparinate].

PMID- 8991045
TI  - [Bone cements and their uses in orthopedics and rheumatology. GRIBOI. Groupe de
      Recherche interdisciplinaire sur les Biomateriaux osteo-articulaires
      injectables].
AB  - Acrylic cement has been used for total hip arthroplasty fixation for several
      years. Use of new cements for bony injections or for treatment of fractures is
      often misunderstood, in spite (or because?) of numerous paper in non-medical
      magazines. Acrylic cement continues to be the reference for bony cements. Most
      hip arthroplasties are still cemented, with good results in most cases, even
      after ten years. Other applications of acrylic cement are reported here,
      especially for percutaneous injection in metastatic vertebral lesions. New kind
      of cements are now available, especially pastes of carbonated apatite, and beta
      tricalcium phosphate-monocalcium phosphate monohydrate water mixtures. With this
      new family of injectable biomaterials we can hope the development of mini
      invasive therapies for bone lesions, and first results appear to be very
      attractive. However continuous improvements of these materials and rigorous
      clinical evaluations are need.

PMID- 8991044
TI  - [Lactic acidosis in alcoholic patients: to think of beriberi].

PMID- 8991046
TI  - [Cornea procurement and grafts and number of patients on waiting lists. Data
      collection in France between 1990 and 1994].
AB  - OBJECTIVES: Analyze annual corneal graft procurement and transplantation in
      France. METHODS: Data collected from all public and private health centers in
      France in a survey conducted in August 1994 by the general health directory were
      analyzed by the French Graft authorities. RESULTS: Between 1990 and the first
      semester 1994, an annual mean of 3205 corneal grafts were performed in France.
      The annual number of grafts fell by 27% between 1991 and 1992 then stabilized at
      2700 grafts per year. Eighty percent of the grafts were performed in public
      institutions. Less than 4% of the patients were foreigners. The number of
      patients on waiting lists on June 30, 1994 was 7129, i.e. 2.7 times the number of
      transplantations in 1993. Mean annual cornea procurement between 1991 and the
      first semester 1994 was 2930. Corneas were removed at the morgue in 78% of the
      cases or in the operating room in 19% (multiple organ procurement) and 1.5%
      (cornea alone). Grafted corneas came from public hospitals in 72% of the cases.
      Fifty-seven percent of the grafts used in private institutions were imported. The
      mean annual number of imported corneas can be estimated at 280. This number has
      increased by 127% since 1990 and corresponds to 8% of the grafted corneas.
      CONCLUSION: The number of corneal grafts in France is similar to that in other
      European countries, but the number of patients on waiting lists is high and
      French eye banks had a restricted role.

PMID- 8991047
TI  - [Congenital toxoplasmosis: contribution of postnatal biological follow-up].
AB  - OBJECTIVES: The diagnosis of congenital toxoplasmosis includes a postnatal follow
      up, often preceded by a prenatal diagnosis. The aim of our study was to assess
      the performances of the different techniques used and the value of the samples in
      the postnatal biological diagnosis. METHODS: The methods available between 1985
      and 1993 consisted in the detection of: i) Toxoplasma gondii in the placenta; ii)
      anti-T. gondii IgM in infant's blood by enzyme-linked immuno-sorbent assay
      (ELISA), immuno-sorbent agglutination assay (ISAGA) and indirect immuno
      fluorescence (IFI), and anti-T. gondii IgG by ELISA and IFI; and iii) neo
      synthetized anti-T. gondii IgG and IgM by enzyme-linked immuno-filtration assay
      (ELIFA). RESULTS: Among 400 cases of seroconversion diagnosed during pregnancy, a
      sure diagnosis with complete follow-up could be established for 104 infants; 37
      of them had proven congenital toxoplasmosis (CT+) while 75 had no congenital
      toxoplasmosis (CT-). Biological arguments supporting congenital toxoplasmosis had
      been observed as early as birth in 78.4% of CT+ cases and before two months in
      94.6%. The serologic tests were positive in 88.2% of CT+ cases by ELIFA, in 73.0%
      by ISAGA, in 43.3% by ELISA M and in 14.0% by IFI M. ELIFA was the less specific
      method (91.3%). CONCLUSION: The sensitive techniques (ELIFA and ISAGA), were
      essential for the instant follow-up to detect toxoplasmic infection as early as
      birth.

PMID- 8991048
TI  - [Magnetic resonance angiography. Value for evaluating the patency of
      aortocoronary bypass].
AB  - OBJECTIVE: Assessment of coronary bypass patency with conventional angiography
      can be limited by difficulties in selective catheterism. The aim of this work was
      to determine whether ultrarapid sequences proposed for imaging coronary arteries
      could be used to evaluate bypass patency. METHODS: Twenty patients (mean age 66
      +/- 7 years) with 42 aorto-coronary bypasses (32 venous and 10 mammary bypasses)
      underwent conventional angiography and magnetic resonance angiography within a 1
      week interval. All patients were evaluated 1 to 15 years after bypass surgery.
      Magnetic resonance imaging (MRI) was performed in ventral supine position using a
      flexible surface coil. Breathhold electrocardiogram-synchronized sequences were
      acquired using a 1.5 T magnet, with TR = 156 ms, TE = 8 ms, slice thickness 5 mm,
      126.256 matrix, and a 7 to 11 segmentation per cardiac cycle. At most, 24
      transverse slices were acquired for each patient. RESULTS: Twenty-six patent
      bypasses were correctly identified with MRI. Three bypass were patent on
      angiography and appeared occluded on MRI (2 mammary and 1 venous bypass). Nine
      bypasses were classed as occluded with both techniques. MRI demonstrated patency
      in one bypass for which selective catheterism was not possible. The sensitivity
      of MRI for the diagnosis of patency in aorto-coronary bypasses was 89% with a 92%
      specificity. MRI did not identify 1 out of 4 bypass stenoses. CONCLUSION: We
      conclude that the ultrarapid breath-hold magnetic resonance sequences can be used
      to determine patency of aorto-coronary bypasses with good sensitivity and
      specificity. Our results would suggest however that this method is inadequate for
      the diagnosis of bypass stenosis.

PMID- 8991049
TI  - [Geographical distribution of epilepsy in the world].
AB  - Based on more than one hundred epidemiological studies we evaluated the frequency
      of epileptic seizures and epilepsy itself. Worldwide, there appears to be unequal
      distribution of disease incidence and prevalence. It seems that the incidence of
      epilepsy in developing countries would be greater than that in the industrialized
      world and that the differences in prevalence observed between the developing and
      the industrialized countries could be epidemiologically significant. Once the
      methodological biases that might account for these differences have been
      eliminated, it is probable that the differences in incidence and prevalence could
      be explained by specific risk factors. Particular regional distribution of the
      disease would then reflect local risk factors and, therefore represent
      epidemiological markers of particular regional or endemic infections, hereditary
      predispositions, early interventions during management of childbirth and
      childhood development or even the natural course of the disease.

PMID- 8991050
TI  - [Amnioinfusion: indications and results].
AB  - Amnioinfusion is a recent procedure introduced for routine obstetrical care
      fifteen years ago. The most widely recognized indication for amnioinfusion is in
      labor, to reduce fetal distress due to variable decceleration associated with
      oligohydramnios and probable presence of thick meconium stained amniotic fluid.
      During pregnancy, amnioinfusion can help in the diagnosis and morphologic
      evaluation in case of anamnios. The indication for amnioinfusion in the
      management of oligohydramnios at term before labour remains controversial. As a
      new procedure amnioinfusion must be managed with extreme caution.

PMID- 8991051
TI  - [Actions of dehydroepiandrosterone: possible links with aging].
AB  - Dehydroepiandrosterone (DHEA) and its sulfo-conjugated derivative (SDHEA),
      secreted by the adrenal glands, are the most abundant circulating steroids in the
      human organism. The well-established fact that levels decrease progressively with
      age suggests a role in the aging process. They could also play a preventive role
      via an antitumoral action, stimulation of the immune system, an antiosteoporotic
      effect, a neuropsychologic action and cardiovascular protection. Nevertheless, it
      is not certain that evidence obtained from animal models can be transposed to man
      due to the specific nature of adrenal secretion of steroids in the human species.
      Epidemiological studies have often provided conflicting results. There have been
      few trials of administration in man, mostly aimed at studying the metabolic
      effects of DHEA. There is no evidence of secondary effects. Inversely, high-doses
      lead to transformation into active androgens with deleterious metabolic effects.
      Consequently, the current trend is to use low doses. Body weight, body
      composition, and sensitivity to insulin are not modified although variable
      effects on the lipid profile have been observed. Finally one study has produced
      much debate: a randomized trial demonstrating an improvement in wellbeing...
      Confirmation of this effect is certainly needed. In the absence of a satisfactory
      animal model, randomized prospective studies versus placebo are required to study
      the effect of substitution therapy in elderly subjects.

PMID- 8991052
TI  - [Perforation of the nasal septum in hemorrhagic rectocolitis].

PMID- 8991053
TI  - [Vasovagal syncope induced by large varices of the lower limbs].

PMID- 8991054
TI  - [Muscular hypertrophy and multifocal motor neuropathy].

PMID- 8991055
TI  - [Functioning and evaluation of a diabetes education unit].

PMID- 8991056
TI  - State of the art in transgenic animals in mutation research.

PMID- 8991057
TI  - Spontaneous mutation in Big Blue transgenic mice: analysis of age, gender, and
      tissue type.
AB  - A lacI-containing transgenic mouse mutation detection system (Big Blue) was used
      to determine the frequency and spectrum of spontaneous mutation in two rapidly
      dividing tissues (male germ cells and thymus) and one slowly dividing tissue
      (brain) at 3 and 10 months of age. By screening 9.4 million lambda plaques, a
      total of 343 circular mutant plaques were recovered from the three tissues. The
      mutation frequencies and spectra were determined by sequencing the lacI gene and
      associated lacZ operator in all samples and correcting for "jackpot" mutations.
      The mutation frequencies and spectra were similar in all three tissues and there
      were no age-dependent or gender-dependent changes. When the mutation spectrum in
      each tissue was compared by utilizing large numbers of independent mutations
      (average: 75 per tissue), there was evidence for small tissue-specific
      differences. The spectrum of "jackpot" mutations, which clearly represents in
      vivo mouse-derived mutations, was similar to that of nonjackpot mutations,
      providing additional evidence that observed mutations occur in mouse. In the
      aggregate, the results suggest that there is: (i) a core mutation frequency and
      spectrum that is modified weakly by tissue-specific metabolism, and (ii) a steady
      state level of spontaneous mutation in adult mice reflecting the balance between
      the accumulation of new mutations and the elimination of mutated cells by either
      selection against suboptimal cellular function or apoptosis triggered by
      accumulated DNA damage.

PMID- 8991058
TI  - A test for neutrality of mutations of the lacZ transgene.
AB  - Neutral mutations are stable alterations in DNA that are neither beneficial nor
      damaging to the cell. Once a mutation is fixed in the DNA, the mutant frequency
      should increase to its maximum and plateau thereafter, provided that enough
      expression time is given. Evidence has been obtained indicating neutrality for
      the endogenous Dlb-1 locus and for the lacl in the BigBlue transgenic system, and
      is reported here for lacZ in the Muta Mouse system. We have found that, after an
      acute dose of ethylnitrosourea (ENU, 250 mg/kg) the mutant frequency for both
      lacZ transgene and Dlb-1 remained constant between 10 and 70 days after
      mutagenesis in the small intestine, where cell turnover is rapid (approximately 7
      days). The same concept should apply to other tissues.

PMID- 8991059
TI  - Temporal and molecular characteristics of lacZ mutations in somatic tissues of
      transgenic mice.
AB  - In order to help establish criteria for optimizing protocols for in vivo mutation
      studies, lacZ transgenic mice (Muta mouse) were treated with five consecutive
      daily doses of ethylnitrosourea (50 mg/kg), sampled at times up to 55 days after
      treatment, and mutant frequencies and DNA sequences determined for liver and bone
      marrow. In the bone marrow, the mutant frequency rose very rapidly in the first 5
      days after treatment to 34 times the control frequency. Subsequently, there was a
      brood peak where the mutant frequency did not vary significantly, although it did
      appear to begin to decline after 45 days. In contrast, in the liver, the peak
      mutant frequency (11 times the control frequency) was not achieved until 35 days,
      after which there appeared to be a slow decline up to 55 days, which was not
      statistically significant. Once the maximum mutant frequency was reached, the
      mutation spectra in the two tissues were indistinguishable. In contrast to the
      G:C-->A:T transitions in 5'-CpG sites characteristic of untreated mice, A:T-->T:A
      transversions and A:T-->G:C transitions were prominent in both liver and bone
      marrow of ENU-treated mice, suggesting the involvement of unrepaired O2- and O4
      ethylthymine adducts. In addition, G:C-->T:A transversions were induced in liver.
      This study demonstrates the possibility that although tissues may have different
      mutation fixation times, a single mutation fixation time equal to the longest
      time may be appropriate for in vivo mutation studies, provided that the mutation
      frequency does not decline appreciably after the peak is reached. This study also
      illustrates the necessity of ensuring that mutation characteristics are
      determined after optimal fixation has occurred.

PMID- 8991061
TI  - Why do stem cells exist?
AB  - Self-renewing tissues have a differentiation hierarchy such that the stem cells
      are the only permanent residents of the tissue, and it is in these cells that
      most cancerous mutations arise. The progeny of the stem cells either remain stem
      cells or enter a transient proliferating cell population that differentiates to
      produce the functional cells of the tissue. The reason that this differentiation
      hierarchy exists has not been established. We show here that alternative
      hierarchies, in which there would be no stem cells, are feasible and biologically
      plausible. We show that current evidence from somatic mutation frequencies at
      both transgenic and endogenous loci implicates cell division in the origin of
      most somatic mutations. We suggest, therefore, that the existence of stem cells
      is an evolutionary consequence of a selective pressure to avoid cancer by
      reducing the number of somatic mutations. The stem cell hierarchy reduces the
      number of cell divisions of those cells that reside permanently in the tissue,
      which reduces the number of somatic mutations and thus minimizes the cancer rate.
      In the small intestine, the existence of stem cells reduces the mutant frequency
      in the stem cells by about one order of magnitude. Since two or more mutations
      are required to transform a cell, the protective effect may be 100-fold or more.
      Similar factors may be expected in other tissues.

PMID- 8991060
TI  - Spontaneous and ethylnitrosourea-induced mutation fixation and molecular spectra
      at the lacI transgene in the Big Blue rat-2 embryo cell line.
AB  - Big Blue Rat-2 cells were evaluated for mutagenesis and mutational spectra
      (spontaneous and ethylnitrosourea [ENU]-induced). Survival, mutant frequency,
      population doubling time, and kinetics of mutant increase (to 120 hr) were
      determined. Exposures were 100, 200, 400, 600, and 1,000 micrograms ENU/ml. The
      spontaneous mutant frequency was similar to that previously reported in vivo,
      i.e., 5 X 10(5). Dose-related increases in mutant frequency were observed
      following ENU treatment. Kinetics (time course) of mutant frequency increase,
      population doubling, and mutational spectra were investigated following treatment
      at 1,000 micrograms ENU/ml. Among 39 spontaneous mutants, 26 independent
      mutations were found as follows: nine (34.6%) G:C-->A:T transitions (five at CpG
      sites), six (23%) G:C-->T:A transversions, three (11.5%) G:C-->C:G transversions
      (two at CpG sites), two (7.7%) frameshifts, five (19%) deletions or insertions,
      and one (3.8%) complex (deletion+insertion) mutation. Among 46 ENU-induced
      mutants, 37 independent mutations (all base substitutions) were found as follows:
      15 (40.5%) G:C-->A:T transitions (four at CpG sites), five (13.5%) A:T-->G:C
      transitions, four (10.8%) G:C-->T:A transversions, 11 (30%) A:T-->T:A
      transversions, and two (5.4%) A:T-->C:G transversions. Nearly 50% of the base
      substitutions in the ENU-treated cells were at A:T base pairs, in contrast to the
      spontaneous mutants where none was found. Both the spontaneous and the ENU
      induced mutational spectra were similar to that reported in vivo and for other
      cells. An important aspect of the experiment is that all mutations sequenced
      following ENU treatment (1,000 micrograms/ml) occurred under conditions which our
      experiments show corresponded to very little mitotic activity.

PMID- 8991062
TI  - Mutagenic response to benzene and tris(2,3-dibromopropyl)-phosphate in the lambda
      lacI transgenic mouse mutation assay: a standardized approach to in vivo mutation
      analysis.
AB  - The genotoxic response of benzene and tris(2,3-dibromopropyl)-phosphate (TDBP)
      have been evaluated in several tissues using the standardized lambda/lacI (Big
      Blue) transgenic mouse mutation assay. Separate groups of four to five male
      B6C3F1 transgenic lambda/lacI mice were given oral administrations of benzene or
      TDBP at varying concentrations. Tissues evaluated include lung, bone marrow, and
      spleen in benzene-treated animals, and liver, kidney, and stomach in TDBP-treated
      animals. Significant increases in lacI mutations were observed in the spleen and
      bone marrow of benzene treated mice, and the kidneys of TDBP-treated mice. Where
      applicable, mutagenesis patterns of tissue sensitivity were consistent with what
      has been observed previously in other assays. In addition, mutagenicity in
      tissues not traditionally evaluated for mutations correlated to sites of
      carcinogenicity for the chemicals tested.

PMID- 8991063
TI  - Organ variation in the mutagenicity of dimethylnitrosamine in Big Blue mice.
AB  - Organ specificity in the lacI mutant frequency (MF) induced by
      dimethylnitrosamine (DMN) was analyzed in lung, liver, kidney, bone marrow,
      urinary bladder, and testis of Big Blue mice. Cell proliferative activity was
      also analyzed in some of these tissues by immunohistochemical staining of
      proliferating cell nuclear antigen (PCNA). Clastogenicity of DMN was
      concomitantly analyzed by the peripheral blood micronucleus assay with the same
      animals used for the lacI mutation assay. Five daily intraperitoneal (i.p.)
      treatments with DMN (1 mg/kg) increased MF in liver (6.2 x control), kidney (2.4
      x control), and lung (2.1 x control). These are known target organs for DMN
      carcinogenesis. No MF increase was observed in nontarget organs studied, i.e.,
      bone marrow, bladder, and testis. Single ip treatment with DMN also increased
      lacI MF in liver but the increases were smaller than in a 5-daily-treatment
      regimen. This result suggests that multiple dosing is more effective in the
      transgenic mutation assay. The enhancement of cell proliferation observed was in
      bronchial epithelia 7 days after treatment. No micronucleus induction in
      peripheral blood was observed 24 hours after 2 and 3 daily ip treatments with 1
      mg/kg DMN. An increase in the incidence of micronucleated reticulocytes in
      peripheral blood was observed 48 hours after single ip treatment with 5 or 10
      mg/kg DMN. The present study demonstrated organ-specific induction of gene
      mutations by DMN which suggests a relevance of this assay for the prediction of
      organ-specific carcinogenesis.

PMID- 8991064
TI  - Evaluation of the in vivo genotoxic potential of three carcinogenic aromatic
      amines using the Big Blue transgenic mouse mutation assay.
AB  - Three genotoxic mouse carcinogens, 4-chloro-o-phenylenediamine (4-C-o-PDA), 2
      nitro-p-phenylenediamine (2-N-p-PDA), and 2,4-diaminotoluene (2,4-DAT), were
      tested in the Big Blue transgenic mouse mutation assay. Each experiment consisted
      of a vehicle control group with ten Big Blue C57BL/6 mice, five of either sex,
      and an equally sized group treated with a high dose of the test chemical. In
      addition, four animals were treated with the vehicle and six animals with the
      test compound for the measurement of bromodeoxyuridine (BrdU) incorporation to
      determine cellular proliferation. Prior to the mutagenicity experiments, the
      maximally tolerated dose of each compound was determined using nontransgenic
      C57BL/6 mice. Based on these results the doses used in the main study were 200
      mg/kg/day for 4-C-o-PDA, 150 mg/kg/ day for 2-N-p-PDA, and 80 mg/kg/day for 2,4
      DAT. Animals were treated for 10 days over a 2 week period and were killed 10
      days after the ast treatment. In an additional experiment with 2,4-DAT, animals
      were killed 28 days after treatment. Since all three chemicals are liver
      carcinogens in the mouse, the DNA of the liver was analyzed using the standard
      procedures for the Big Blue assay. Hepatocyte proliferation was assessed by
      immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and,
      in some studies, by measuring BrdU incorporation. 4-C-o-PDA and 2-N-p-PDA did not
      induce an increase in PCNA expression when measured 10 days after the last
      treatment. There was no increase in BrdU incorporation immediately after
      treatment with 4-C-o-PDA or with 2,4-DAT. However, 10 days after the last
      treatment with 2,4-DAT, a strong mitogenic effect was found with both techniques,
      i.e., in the PCNA and BrdU assays. 4-C-o-PDA, a liver carcinogen in both genders
      of mice, induced a small, statistically significant increase of the mutant
      frequencies in females. No increase was found in males. 2-N-p-PDA, which has been
      reported to induce liver tumors only in females, was found positive in males and
      was clearly negative in females. 2,4-DAT, a liver carcinogen in female mice, was
      positive in females and negative in males when the animals were killed 10 days
      after the last treatment. After an expression time of 28 days, 2,4-DAT induced a
      statistically significant increase in both sexes. The effect in females was
      marginally stronger than after 10 days' expression time and almost identical to
      the effect observed in males under these test conditions. In conclusion, the
      experiments showed that the Big Blue assay detects the genotoxicity of the three
      carcinogenic monocyclic aromatic amines tested. However, it seems that the sex
      specificity of the carcinogenic effects of these compounds is not reflected by
      the mutagenicity data in Big Blue mice.

PMID- 8991065
TI  - Organ variation in the mutagenicity of ethylnitrosourea in Muta mouse: results of
      the collaborative study on the transgenic mutation assay by JEMS/MMS. The
      Collaborative Study Group for the Transgenic Mouse Mutation Assay Mammalian
      Mutagenesis Study Group of the Environmental Mutagen Society of Japan.
AB  - A collaborative study of the transgenic mouse mutation assay was performed by a
      subgroup of the Mammalian Mutagenesis Study Group (MMS), which is a
      suborganization of the Environmental Mutagen Society of Japan (JEMS). Twenty-six
      laboratories participated in this collaboration, and ethylnitrosourea (ENU)
      mutagenesis was studied in eight organs of lacZ transgenic mice (Muta Mouse)
      liver, spleen, bone marrow, brain, lung, kidney, urinary bladder, and heart. Mice
      were treated by a single intraperitoneal (ip) injection of 150 mg/kg ENU, and the
      lacZ mutant frequency (MF) was analyzed by positive selection after 3- and 14-day
      expression times. The MF in the control group was similar for all organs,
      approximately 40-60 x 10(-6). ENU increased MF in all organs except the brain
      with the highest values (more than 10 times the control value) observed in bone
      marrow on days 3 and 14, and in spleen on day 14. The MF in urinary bladder
      increased over 400 x 10(-6) and MFs in liver and lung were more than 150 x 10(-6)
      on day 14, although no increases were apparent in these organs on day 3.
      Approximately a doubling of control values was observed in kidney and heart but
      these were less than 100 x 10(-6). These results demonstrated that ENU induces
      organ specific mutagenesis with specific expression periods.

PMID- 8991066
TI  - Mutagenic response of the endogenous hprt gene and lacI transgene in
      benzo[a]pyrene-treated Big Blue B6C3F1 mice.
AB  - Big Blue (BB) and generic B6C3F1 mice were given one to three i.p. injections of
      50 mg/kg benzo[a]pyrene (B[a]P) in DMSO every other day to achieve cumulative
      doses of 50 to 150 mg/kg. Three weeks after treatment, the mutation frequency at
      the endogenous hprt gene and lacI transgene was measured in splenic T cells.
      Generic mice given 50, 100, and 150 mg/kg B[a]P displayed induced hprt
      frequencies (observed hprt frequency minus control frequency) of 5.5 +/- 1.0, 11
      +/- 2.0, and 19 +/- 2.6 x 10(-6), respectively (average +/- SEM). In contrast, BB
      mice given 50 and 150 mg/kg B[a]P displayed induced hprt frequencies of 0.9 +/-
      0.6 and 9.1 +/- 1.5 x 10(-6). 32P postlabelling revealed that the lower hprt
      response in BB mice correlated with lower amounts of BP-DNA adducts in spleen,
      liver, and lung 24 hours after B[a]P exposure. Western blot analysis of liver
      samples from B[a]P-treated mice suggests that the reduced adduct load in turn may
      be due to lower P450 1A1 levels in BB mice. The frequency of induced, nonsectored
      blue plaques (observed blue plaque frequency minus control frequency) in BB mice
      receiving 50 and 150 mg/kg B[a]P was 41 +/- 9 and 134 +/- 10 x 10(-6) (15- to 40
      fold higher than the induced hprt frequency in the same treated animals).
      Sectored plaques were observed in both control and B[a]P groups but their
      frequency showed no relationship to dose (sectored frequency in all groups was
      approximately 20 x 10(-6)). To test whether persistent DNA adducts in the
      packaged lambda vector were contributing to the observed blue plaque frequency,
      purified lambda-LIZ DNA was treated in vitro with B[a]P diol epoxide (BPDE),
      packaged, and plated on E. coli lawn cells. Treatment with BPDE did not produce
      significant increases in homogeneous blue plaques, suggesting that the majority
      of mutants obtained from B[a]P-treated BB mice occurred in vivo. These results
      indicate that B[a]P exposure produces many more mutations at the lacI transgene
      than at the endogenous hprt locus.

PMID- 8991067
TI  - The genetic analysis of lacI mutations in sectored plaques from Big Blue
      transgenic mice.
AB  - The Big Blue lacI transgenic rodent assay, which uses the lambda LIZ/lacI gene as
      the target for mutation, provides a convenient short-term assay for the study of
      mutation in vivo [Kohler et al. (1991): Proc Natl Acad Sci USA 88:7958-7962;
      Provost et al. (1993): Mutat Res 288:133-149). However, the interpretation of
      data from transgenic animal assays is sometimes complicated by mutants that
      appear as sectored mutant lambda plaques. These mutants can form a significant
      fraction of the mutant plaques [Hayward et al. (1995): Carcinogenesis 16:2429
      2433]. Thus, in order to accurately determine in vivo mutant frequencies and
      mutational specificities, it is necessary to score sectored plaques and partition
      them from the rest of the data. In this study, the specificity of mutation in
      sectored plaques recovered from untreated and UVB-treated Big Blue mouse skin was
      analyzed and compared to mutations recovered from lambda LIZ/lacI grown on the
      Escherichia coli host. The mutational spectra of sectored plaques from untreated
      and UVB-treated mice were remarkably similar to each other and resembled those
      recovered from the lambda LIZ/lacI phage plated directly on E. coli. Both the
      sectored mutants and those recovered in lambda LIZ/lacI phage differed from the
      spectra of spontaneous mutants in E. coli and in Big Blue mouse skin. While
      sectored mutants from UVB-treated mouse skin and lambda LIZ/lacI mutants were
      also different from spontaneous mutants recovered from Big Blue liver, these was
      little difference between sectored mutants from untreated mouse skin and
      spontaneous liver mutants (P = 0.07). The mutational spectra of sectored plaques
      is thus largely consistent with their origin as spontaneous mutations arising in
      vitro during growth of the lambda LIZ/lacI shuttle vector DNA on the E. coli
      host, although the potential contribution from lesions in mouse DNA being
      expressed ex vivo in the E. coli host cannot be excluded.

PMID- 8991068
TI  - An efficient laboratory protocol for the sequencing of large numbers of lacI
      mutants recovered from Big Blue transgenic animals.
AB  - Mutational spectra provide a powerful approach to investigate both the mutagenic
      potential and the mechanism of action of suspected mutagens and carcinogens.
      Recently, transgenic techniques have made it possible to generate mutational
      spectra in animals. Such a spectrum may consist of 50 to 200 mutants depending on
      the nature of the mutations, and many spectra can be generated depending on the
      design of the experiment. This report describes a practical approach for the
      processing and sequencing of large numbers of lacI mutants recovered from Big
      Blue animals.

PMID- 8991069
TI  - Database and software for the analysis of mutations at the lacI gene in both
      transgenic rodents and bacteria.
AB  - The use of transgenic rodents for the study of genetic toxicology has increased
      dramatically in the past several years. A great deal of the recent work has
      employed the lacI locus in transgenic mice. In addition to the transgenic data, a
      substantial amount of information exists regarding mutation of the lacI gene in
      bacteria. In an effort to centralize the information regarding mutations in the
      lacI gene in both rodents and bacteria, we have created a computerized database
      that contains information about DNA sequence alterations on about 500 mutations
      in transgenic rodents and 8,000 mutations in bacteria. We have also produced a
      software package for the analysis of the lacI database. Routines have been
      developed for the analysis of single base substitutions, including programs to
      (i) determine if two mutational spectra are different; (ii) determine if
      mutations show a DNA strand bias; (iii) determine the frequency of transitions
      and transversions; (iv) display the number and kind of mutations observed at each
      base in the coding region; (v) perform nearest neighbor analysis; and (vi)
      display mutable amino acids in the lacI protein. The software runs only on IBM
      compatible machines running Microsoft Windows. The software and lacI database are
      freely available via the internet (http:/(/)sunsite.unc.edu/dnam/mainpage.++
      +html).

PMID- 8991070
TI  - Mutational spectra in transgenic animal research: data analysis and study design
      based upon the mutant or mutation frequency.
AB  - Understanding chemically induced changes in mutational spectra can aid in
      deciphering mechanisms of mutagenesis. In this paper, we propose the use of
      statistical methods that are based upon the mutation frequency, rather than
      simple mutant counts which have no relationship to the mutation frequency. These
      methods have a number of advantages over the current standard analysis: an
      improved means of identifying those classes/sites of mutation which have
      treatment-related induction, greater sensitivity to localized differences in
      spectra (e.g., limited to a single base pair), one-sided tests for induction of
      mutations, tests of dose-response, and a framework for sample-size estimation in
      terms of the number of mutants to sequence. As examples, the methods are applied
      to data from transgenic mutation assays.

PMID- 8991071
TI  - Mutation frequencies but not mutant frequencies in Big Blue mice fit a Poisson
      distribution.
AB  - Transgenic mutation assays generally use mutant frequencies to estimate mutation
      frequencies but the degree to which clonal expansion inflates mutant frequencies
      is largely unknown. Mutant frequency is defined as the fraction of cells carrying
      mutations in the gene of interest and, according to the standard Big Blue
      protocol, is determined by dividing the number of mutant plaques by the total
      number of plaques screened. Mutation frequency is determined as the fraction of
      cells carrying definitely independent mutations and therefore requires correction
      for clonal expansion. Mutant and mutation frequencies were determined for brain,
      thymus and male germ cells of four mice from two age groups (3-versus 10-month
      old). The mutant frequency in thymus differed significantly between 3- and 10
      month old mice (P < 0.05). By sequencing all mutants, the mutation frequency
      (i.e., corrected for jackpot mutations) in thymus was determined and was not
      significantly different between 3- and 10-month old mice. Mutant frequency does
      not fit a Poisson distribution, but mutation frequency corrected for jackpot
      mutations is substantially less variable and does fit a Poisson distribution.

PMID- 8991072
TI  - Spectrum of mutations in kidney, stomach, and liver from lacI transgenic mice
      recovered after treatment with tris(2,3-dibromopropyl)phosphate.
AB  - The flame retardant tris(2,3-dibromopropyl)phosphate (TDBP), once used in cotton
      sleep wear for children, is presently banned from commerce. It produces tumors in
      rodents in both a sex- and tissue-specific manner. The kidney is the main target
      for tumor formation in male and female rats, as well as in male mice. In
      contrast, tumors are formed in the liver of female animals. We have used lacI
      transgenic male B6C3F1 mice (Big Blue) to examine the induction of mutation in
      kidney, liver, and stomach after exposure to 150 mg/kg (2 days), 300 mg/kg (4
      days), and 600 mg/kg (4 days) of TDBP. At the highest dose, the mutant frequency
      was approximately 50% above control values in the kidney (P < 0.01). A smaller
      increase was observed in the liver (P = 0.07), while no increase was seen in the
      stomach (P = 0.28). Sequence analysis of the recovered mutants showed a TDBP
      specific change in mutation spectrum in kidney, which was not observed in liver
      and stomach. In kidney, a dose-dependent decrease in G:C-->A:T transitions,
      including at 5'-CpG-3' sites, was observed. This was accompanied by an increase
      in the loss of single G:C base pairs from approximately 3% to 15%. These results
      illustrate both the sensitivity and specificity of the lacI transgenic system in
      the analysis of tissue-specific mutation. This study also reinforces the
      importance of examining mutational spectra when mutant induction levels are low.

PMID- 8991073
TI  - Assessment of 1,3-butadiene mutagenicity in the bone marrow of B6C3F1 lacI
      transgenic mice (Big Blue): a review of mutational spectrum and lacI mutant
      frequency after a 5-day 625 ppm 1,3-butadiene exposure.
AB  - 1,3-Butadiene (BD) is a carcinogen that is bioactivated to at least two genotoxic
      metabolites. In the present article, we review briefly our previous studies on
      the in vivo mutagenicity and mutational spectra of BD in bone marrow and extend
      these studies to examine the effect of exposure time (5-days vs. 4-week exposure
      to 625 ppm BD used in previous studies) on the lacI mutant frequency in the bone
      marrow. Inhalation exposure to BD at 625 ppm and 1,250 ppm mutagenic in vivo,
      inducing an increase in the transgene mutant and mutation frequency in the bone
      marrow. Analysis of the mutational spectrum in BD-exposed and air control mice
      demonstrated that BD exposure induced an increased frequency of mutations at A:T
      base pairs. There was no difference in the lacI mutant frequency determined in
      the bone marrow between a short-term exposure to BD (5 days) and a longer-term
      exposure (4 weeks). These data taken together demonstrate that inhalation
      exposure to BD induces in vivo somatic cell mutation.

PMID- 8991074
TI  - Mutational spectra of tamoxifen-induced mutations in the livers of lacI
      transgenic rats.
AB  - Tamoxifen, an important drug in breast cancer treatment, causes liver cancer in
      rats. The standard range of in vitro tests have failed to show that it causes DNA
      damage, but 32P-postlabelling and DNA-binding studies have shown that tamoxifen
      forms DNA adducts in rat liver. In 1995 a transgenic rat (Big Blue; Stratagene,
      La Jolla, CA) became available which harbours the bacterial lacI gene, thereby
      allowing the in vivo study of tamoxifen mutagenesis. Recently, we [Styles JA et
      al. (1996): Toxicologist 30; 161] showed that tamoxifen caused on increase in the
      mutation frequency at the lacI gene in these transgenic rats. In this study, we
      report on our preliminary analysis of the mutational spectra of 33 control and 38
      tamoxifen-induced mutant lacI genes. Plasmid DNA containing the lacI gene was
      isolated from the mutant phages and its DNA sequence determined. In the control
      animal group, 81% of the mutant lacI genes were point mutations, whilst in the
      tamoxifen-treated group, 62% of the mutant lacI genes were point mutations. Of
      the tamoxifen-induced mutants, 43% were GC-->TA transversions and 70% of point
      mutations. In the control group, GC-->TA transversions were 19% of all mutations
      and 24% of point mutations. Thus, compared with control animals, tamoxifen
      treatment had significantly increased the proportion of GC-->TA transversions.

PMID- 8991075
TI  - A strategy for the application of transgenic rodent mutagenesis assays.
AB  - The past several years have seen an enormous increase in the development and use
      of transgenic animal models to measure mutations in specific inserted reporter
      genes. These systems provide gene mutation data in vivo in a wide range of
      relevant tissues. Numerous laboratories are now using these systems with
      consistent results. This paper describes the unique niche that transgenic
      mutagenesis systems can fill in product development and registration strategies.
      In addition to tissue-specific mechanistic studies, transgenic assays are
      available to follow up mutagenic effects demonstrated in Salmonella, Escherichia
      coli, mouse lymphoma (L5178Y) cells, or other in vitro systems.

PMID- 8991076
TI  - Initial consideration for use of transgenic mutation assays in a regulatory
      submission.
AB  - As an initial consideration for use of TM assays in a regulatory submission, we
      focus here especially on the following questions: (1) What conditions would
      trigger the performance of a TM assay? (2) What data set is sufficient to support
      a negative result? and (3) What increase in mutation frequency is considered to
      be a positive result? In the first question, we discuss outcomes from traditional
      tests such as RM, CA, GM, and MN assays. In the second question, we propose a
      provisional data set including several items, i.e., experimental size [number of
      animals per group, number of plaques per animal (tissue)], tissue selection,
      route of administration, top dose level, number of dosings (single vs. multiple),
      sampling time, number of samples, dose levels, and positive and negative
      controls. Some statistical and biological considerations are needed for the third
      question.

PMID- 8991077
TI  - Parameters affecting the use of the lac repressor system in eukaryotic cells and
      transgenic animals.
AB  - Elements of the lactose operon were used to study parameters affecting gene
      expression in cultured cells and transgenic animals. A Lac repressor protein
      containing a nuclear transport signal was shown to inhibit expression of a
      reporter gene by interacting with lac operator sequences. In cultured cells,
      operator sequence, operator placement and induction parameters were all shown to
      be important for obtaining tight repression of a reporter gene followed by high
      level expression upon induction. Induction levels were also dependent on the
      reporter gene, with the luciferase gene yielding higher induction levels than the
      chloramphenicol acetyltransferase gene. In transgenic animals, the lacI mRNA was
      not detected in the C57BL/6 mouse strain until the animal was exposed to a
      demethylating agent. After 5-azacytidine treatment, expression of lacI mRNA was
      detected in the brain, heart, kidney, lung and ovary. In the FVB transgenic mouse
      strain, expression of lacI mRNA was detected without 5-azacytidine treatment in
      the kidney, liver, lung, and testes. Preliminary experiments with double
      transgenic animals containing both lacI and operator/luciferase transgenes showed
      a decrease in luciferase expression compared to the luciferase-only animals in
      both tissue extracts and transgenic fetal primary cultures, although IPTG
      induction was not achieved in these animals or primary cultures. The
      applicability and challenges of the system for regulation of gene expression are
      discussed.

PMID- 8991078
TI  - Tissue specificity of spontaneous point mutations in lambda supF transgenic mice.
AB  - Transgenic mice carrying multiple copies of a recoverable lambda phage shuttle
      vector carrying the supF mutation reporter gene (lambda supF) were constructed
      for the purpose of studying mutagenesis in a whole animal. Spontaneous mutations
      in rescued supF target genes from mouse liver and skin were analyzed. The
      mutation frequency was similar in both tissues (in the range of 2 x 10(-5)), but
      the spectrum of point mutations was distinct, with transitions common in the skin
      and transversions more prominent in the liver (P = 0.01). These results may help
      to elucidate pathways of endogenous mutagenesis in vivo, and they illustrate
      potentially important tissue-specific differences in genetic instability.

PMID- 8991079
TI  - A new transgenic mouse mutagenesis test system using Spi- and 6-thioguanine
      selections.
AB  - A new transgenic mouse mutagenesis test system has been developed for the
      efficient detection of point mutations and deletion mutations in vivo. The mice
      carry lambda EG10 DNA as a transgene. When the rescued phages are infected into
      Escherichia coli YG6020-expressing Cre recombinase, the phage DNA is converted
      into plasmid pYG142 carrying the chloramphenicol-resistance gene and the gpt gene
      of E. coli. The gpt mutants can be positively detected as colonies arising on
      plates containing chloramphenicol and 6-thioguanine. The EG10 DNA carries a chi
      site along with the red and gam genes so that the wild-type phages display Spi-
      (sensitive to P2 interference) phenotype. Mutant phages lacking both red and gam
      genes can be positively detected as plaques that grow in P2 lysogens of E. coli.
      These mutant phages are called lambda Spi-. The spontaneous gpt mutation
      frequencies of five independent transgenic lines were 1.7 to 3.3 x 10(-5) in bone
      marrow. When the mice were treated with ethylnitrosourea (single i.p. treatments
      with 150 mg/kg body weight; killed 7 days after the treatments), mutation
      frequencies were increased four- to sevenfold over the background in bone marrow.
      The average rescue efficiencies were more than 200,000 chloramphenicol-resistant
      colonies per 7.5 micrograms bone marrow DNA per packaging reaction. In contrast
      to gpt mutation frequencies, spontaneous Spi- mutation frequencies were 1.4 x 10(
      6) and 1.1 x 10(-6) in bone marrow and sperm, respectively. No spontaneous Spi-
      mutants have been detected so far in spleen, although 930,000 phages rescued from
      untreated mice were screened. In gamma-ray-treated animals, however, induction of
      Spi- mutations was clearly observed in spleen, at frequencies of 1.4 x 10(-5) (5
      Gy), 1.2 x 10(-5) (10 Gy), and 2.0 x 10(-5) (5O Gy). These results suggest that
      the new transgenic mouse "gpt delta" could be useful for the efficient detection
      of point mutations and deletion mutations in vivo.

PMID- 8991080
TI  - APRT: a versatile in vivo resident reporter of local mutation and loss of
      heterozygosity.
AB  - We describe an in vivo mutagenesis model that utilizes reverse mutation and
      forward mutation at the endogenous Aprt locus. Reverse mutation provides an in
      situ method for detecting environments or agents that cause point mutations.
      Forward mutation detects large chromosomal events, including mitotic
      recombination, chromosome loss, and large multilocus deletion, all of which can
      lead to loss of heterozygosity. Detection of reverse mutation in vivo is based on
      the differential capacity of Aprt and Aprt cells to sequester radiolabeled
      adenine by catalyzing its conversion to adenosine monophosphate with subsequent
      incorporation into nucleic acids. Cells lacking APRT activity cannot accumulate
      exogenously administered, tagged adenine, whereas Aprt+ cells can and will
      thereby become marked. Thus, genetically modified mice with mutant but revertible
      Aprt alleles should be a useful vehicle for in situ detection of mutagenic
      activity in the whole animal. the feasibility of this model has been illustrated,
      first, by showing that APRT-deficient mice are viable and, second, by
      demonstrating that the minority of Aprt+ cells within a chimeric tumor growing in
      an Aprt+ mouse can be selectively labeled following IP injection of [14C]-adenine
      and can be identified by autoradiography. Forward mutation, detected by growth in
      selective medium of primary cells derived from Aprt+/- heterozygous mice,
      provides on independent estimate of in vivo mutation frequency. The frequency
      with which Aprt colonies arise provides a measure of the frequency of Aprt(-)
      negative cells in the tissue at that point in time. Culture of skin fibroblasts
      in 2,6-diaminopurine (DAP) produced Aprt+ colonies with a frequency of about 10(
      4). This frequency is similar to that found for human T lymphocytes from
      individuals heterozygous at the Aprt locus. In both cases, the majority of
      mutagenic events involved allele loss. Polymerase chain reaction with linked
      polymorphic microsatellites on mouse chromosome 8 demonstrated that allele loss
      was mediated mostly by mitotic recombination, as was the case for human T
      lymphocytes. The high frequency of mitotic recombination and allele loss at a
      neutral locus has significant implications for the process of tumorigenesis and
      argues that spontaneous or induced mitotic recombination may play a causal role
      in the progression to cancer.

PMID- 8991081
TI  - Development of a novel mouse tk+/- embryonic stem cell line for use in
      mutagenicity studies.
AB  - A tk+/- mouse embryonic stem (ES) cell line, designated 1G2, has been created in
      which one allele of the thymidine kinase (tk) gene was inactivated by targeted
      homologous recombination. This line is an analog of the mouse lymphoma tk+/-
      L5178Y cell line, which is used widely to assess the mutagenicity of chemical
      agents. Treatment of 1G2 cells with the alkylating agent N-ethyl-N-nitrosourea
      (ENU) resulted in a dose-related increase in trifluorothymidine-resistant
      colonies. Mutant frequencies of 152 and 296 per 10(6) cells were determined for
      0.1 and 0.3 mg/ml doses of ENU, compared with a spontaneous mutant frequency of
      15 per 10(6) cells. The data indicate that tk+/- 1G2 ES cells may be useful for
      the creation of a transgenic mouse model for assessing in vivo mutation using an
      endogenous autosomal gene.

PMID- 8991082
TI  - Polo kinase: the choreographer of the mitotic stage?

PMID- 8991083
TI  - In vivo localization of DNA sequences and visualization of large-scale chromatin
      organization using lac operator/repressor recognition.
AB  - We report a new method for in situ localization of DNA sequences that allows
      excellent preservation of nuclear and chromosomal ultrastructure and direct, in
      vivo observations. 256 direct repeats of the lac operator were added to vector
      constructs used for transfection and served as a tag for labeling by lac
      repressor. This system was first characterized by visualization of chromosome
      homogeneously staining regions (HSRs) produced by gene amplification using a
      dihydrofolate reductase (DHFR) expression vector with methotrexate selection.
      Using electron microscopy, most HSRs showed approximately 100-nm fibers, as
      described previously for the bulk, large-scale chromatin organization in these
      cells, and by light microscopy, distinct, large-scale chromatin fibers could be
      traced in vivo up to 5 microns in length. Subsequent experiments demonstrated the
      potential for more general applications of this labeling technology. Single and
      multiple copies of the integrated vector could be detected in living CHO cells
      before gene amplification, and detection of a single 256 lac operator repeat and
      its stability during mitosis was demonstrated by its targeted insertion into
      budding yeast cells by homologous recombination. In both CHO cells and yeast, use
      of the green fluorescent protein-lac repressor protein allowed extended, in vivo
      observations of the operator-tagged chromosomal DNA. Future applications of this
      technology should facilitate structural, functional, and genetic analysis of
      chromatin organization, chromosome dynamics, and nuclear architecture.

PMID- 8991085
TI  - Targeting of membranes to sea urchin sperm chromatin is mediated by a lamin B
      receptor-like integral membrane protein.
AB  - We have identified an integral membrane protein of sea urchin gametes with an
      apparent molecular mass of 56 kD that cross-reacts with an antibody against the
      nucleoplasmic NH2-terminal domain of human lamin B receptor (LBR). In mature
      sperm, p56 is located at the tip and base of the nucleus from where it is removed
      by egg cytosol in vitro. In the egg, p56 is present in a subset of cytoplasmic
      membranes (MV2 beta) which contributes the bulk of the nuclear envelope during
      male pronuclear formation. p56-containing vesicles are required for nuclear
      envelope assembly and have a chromatin-binding capacity that is mediated by p56.
      Lamin B is not present in these vesicles and is imported into the nucleus from a
      soluble pool at a later stage of pronuclear formation. Lamin B incorporation and
      addition of new membranes are necessary for pronuclear swelling and nuclear
      envelope growth. We suggest that p56 is a sea urchin LBR homologue that targets
      membranes to chromatin and later anchors the membrane to the lamina.

PMID- 8991084
TI  - Antibody microinjection reveals an essential role for human polo-like kinase 1
      (Plk1) in the functional maturation of mitotic centrosomes.
AB  - Mammalian polo-like kinase 1 (Plk1) is structurally related to the polo gene
      product of Drosophila melanogaster, Cdc5p of Saccharomyces cerevisiae, and plo1+
      of Schizosaccharomyces pombe, a newly emerging family of serine-threonine kinases
      implicated in cell cycle regulation. Based on data obtained for its putative
      homologues in invertebrates and yeasts, human Plk1 is suspected to regulate some
      fundamental aspect(s) of mitosis, but no direct experimental evidence in support
      of this hypothesis has previously been reported. In this study, we have used a
      cell duplication, microinjection assay to investigate the in vivo function of
      Plk1 in both immortalized (HeLa) and nonimmortalized (Hs68) human cells.
      Injection of anti-Plk1 antibodies (Plk1+) at various stages of the cell cycle had
      no effect on the kinetics of DNA replication but severely impaired the ability of
      cells to divide. Analysis of Plk1(+)-injected, mitotically arrested HeLa cells by
      fluorescence microscopy revealed abnormal distributions of condensed chromatin
      and monoastral microtubule arrays that were nucleated from duplicated but
      unseparated centrosomes. Most strikingly, centrosomes in Plk1(+)-injected cells
      were drastically reduced in size, and the accumulation of both gamma-tubulin and
      MPM-2 immunoreactivity was impaired. These data indicate that Plk1 activity is
      necessary for the functional maturation of centrosomes in late G2/early prophase
      and, consequently, for the establishment of a bipolar spindle. Additional roles
      for Plk1 at later stages of mitosis are not excluded, although injection of Plk1+
      after the completion of spindle formation did not interfere with cytokinesis.
      Injection of Plk1+ into nonimmortalized Hs68 cells produced qualitatively similar
      phenotypes, but the vast majority of the injected Hs68 cells arrested as single,
      mononucleated cells in G2. This latter observation hints at the existence, in
      nonimmortalized cells, of a centrosome-maturation checkpoint sensitive to the
      impairment of Plk1 function.

PMID- 8991086
TI  - Cell fusion during yeast mating requires high levels of a-factor mating
      pheromone.
AB  - During conjugation, two yeast cells fuse to form a single zygote. Cell fusion
      requires extensive remodeling of the cell wall, both to form a seal between the
      two cells and to remove the intervening material. The two plasma membranes then
      fuse to produce a continuous cytoplasm. We report the characterization of two
      cell fusion defective (Fus-) mutants, fus5 and fus8, isolated previously in our
      laboratory. Fluorescence and electron microscopy demonstrated that the fus5 and
      fus8 mutant zygotes were defective for cell wall remodeling/removal but not
      plasma membrane fusion. Strikingly, fus5 and fus8 were a specific; both mutations
      caused the mutant phenotype when present in the MATa parent but not in the MAT
      alpha parent. Consistent with an a-specific defect, the fus5 and fus8 mutants
      produced less a-factor than the isogenic wild-type strain. FUS5 and FUS8 were
      determined to be allelic to AXL1 and RAM1, respectively, two genes known to be
      required for biogenesis of a-factor. Several experiments demonstrated that the
      partial defect in a-factor production resulted in the Fus- phenotype. First,
      overexpression of a-factor in the fus mutants suppressed the Fus- defect. Second,
      matings to an MAT alpha partner supersensitive to mating pheromone (sst2 delta)
      suppressed the Fus- defect in trans. Finally, the gene encoding a-factor, MFA1,
      was placed under the control of a repressible promoter; reduced levels of wild
      type a-factor caused an identical cell fusion defect during mating. We conclude
      that high levels of pheromone are required as one component of the signal for
      prezygotes to initiate cell fusion.

PMID- 8991087
TI  - Involvement of Rabphilin-3A in cortical granule exocytosis in mouse eggs.
AB  - Rabphilin-3A is a putative target protein for Rab3A, a member of the small GTP
      binding protein superfamily that has been suggested to play a role in regulated
      exocytosis in presynapses. In this study we determined the expression and the
      function of Rabphilin-3A in mouse eggs at fertilization. Rabphilin-3A mRNA and
      protein were detected by reverse transcriptase-PCR and immunoblot analysis,
      respectively, in metaphase II mouse eggs. Immunofluorescence analysis showed that
      Rabphilin-3A protein was distributed in the cortical region in eggs. Sperm
      induces cortical granule (CG) exocytosis via an increase in cytosolic Ca2+ at
      fertilization. We microinjected the NH2- or COOH-terminal fragment of recombinant
      Rabphilin-3A into metaphase II eggs. Neither treatments altered the sperm-induced
      cytosolic Ca2+ increase, but both inhibited CG exocytosis in a dose-dependent
      manner. The NH2-terminal fragment was more effective than the COOH-terminal
      fragment. Full-length Rabphilin-3A did not affect CG exocytosis, but it
      attenuated the inhibition of CG exocytosis by the NH2-terminal fragment. These
      results show that Rabphilin-3A is involved in Ca(2+)-dependent CG exocytosis at
      fertilization in mouse eggs.

PMID- 8991088
TI  - Transferrin receptor containing the SDYQRL motif of TGN38 causes a reorganization
      of the recycling compartment but is not targeted to the TGN.
AB  - The SDYQRL motif of the cytoplasmic domain of TGN38 is involved in targeting
      TGN38 from endosomes to the TGN. To create a system for studying this pathway, we
      replaced the native transferrin receptor (TR) internalization motif (YTRF) with
      the SDYQRL TGN-targeting motif. The advantages of using TR as a reporter molecule
      include the ability to monitor trafficking, in both biochemical and microscopy
      experiments, using the natural ligand transferrin. When expressed in CHO cells,
      the SDYQRL-TR construct accumulated in juxtanuclear tubules and vesicles that are
      in the vicinity of the TGN. The SDYQRL-TR-containing structures, however, do not
      colocalize with TGN markers (e.g., NBD ceramide), and therefore the SDYQRL motif
      is not sufficient to target the TR to the TGN. The morphology of the SDYQRL-TR
      containing juxtanuclear structures is different from the recycling compartment
      found in cells expressing the wild-type TR. In addition, the SDYQRL-TR-containing
      juxtanuclear compartment is more acidic than the recycling compartment in cells
      expressing the wild-type TR. The juxtanuclear compartment, however, is a bona
      fide recycling compartment since SDYQRL-TR was recycled back to the cell surface
      at a rate comparable to the wild-type TR, and sphingomyelin and cellubrevin, both
      of which label all compartments of the endocytic recycling pathway, colocalize
      with SDYQRL-TR in the juxtanuclear structures. These findings demonstrate that
      expression of the SDYQRL-TR construct alters the morphology and pH of endocytic
      recycling compartments rather than selectively affecting the intracellular
      trafficking pathway of the SDYQRL-TR construct. Therefore, the SDYQRL trafficking
      motif is not simply a molecular address that targets proteins to the TGN, but it
      can play an active role in determining the physical characteristics of endosomal
      compartments.

PMID- 8991089
TI  - Multiple PEX genes are required for proper subcellular distribution and stability
      of Pex5p, the PTS1 receptor: evidence that PTS1 protein import is mediated by a
      cycling receptor.
AB  - PEX5 encodes the type-1 peroxisomal targeting signal (PTS1) receptor, one of at
      least 15 peroxins required for peroxisome biogenesis. Pex5p has a bimodal
      distribution within the cell, mostly cytosolic with a small amount bound to
      peroxisomes. This distribution indicates that Pex5p may function as a cycling
      receptor, a mode of action likely to require interaction with additional
      peroxins. Loss of peroxins required for protein translocation into the peroxisome
      (PEX2 or PEX12) resulted in accumulation of Pex5p at docking sites on the
      peroxisome surface. Pex5p also accumulated on peroxisomes in normal cells under
      conditions which inhibit protein translocation into peroxisomes (low temperature
      or ATP depletion), returned to the cytoplasm when translocation was restored, and
      reaccumulated on peroxisomes when translocation was again inhibited.
      Translocation inhibiting conditions did not result in Pex5p redistribution in
      cells that lack detectable peroxisomes. Thus, it appears that Pex5p can cycle
      repeatedly between the cytoplasm and peroxisome. Altered activity of the peroxin
      defective in CG7 cells leads to accumulation of Pex5p within the peroxisome,
      indicating that Pex5p may actually enter the peroxisome lumen at one point in its
      cycle. In addition, we found that the PTS1 receptor was extremely unstable in the
      peroxin-deficient CG1, CG4, and CG8 cells. Altered distribution or stability of
      the PTS1 receptor in all cells with a defect in PTS1 protein import implies that
      the genes mutated in these cell lines encode proteins with a direct role in
      peroxisomal protein import.

PMID- 8991090
TI  - Granule lattice protein 1 (Grl1p), an acidic, calcium-binding protein in
      Tetrahymena thermophila dense-core secretory granules, influences granule size,
      shape, content organization, and release but not protein sorting or condensation.
AB  - The electron-dense cores of regulated secretory granules in the ciliate
      Tetrahymena thermophila are crystal lattices composed of multiple proteins.
      Granule synthesis involves a series of steps beginning with protein sorting,
      followed by the condensation and precise geometric assembly of the granule cargo.
      These steps may to various degrees be determined by the cargo proteins
      themselves. A prominent group of granule proteins, in ciliates as well as in
      vertebrate neuronal and endocrine cells, are acidic, heat-stable, and bind
      calcium. We focused on a protein with these characteristics named granule lattice
      protein 1 (Grl1p), which represents 16% of total granule contents, and we have
      now cloned the corresponding gene. Mutants in which the macronuclear copies of
      GRL1 have been disrupted continue to synthesize dense-core granules but are
      nonetheless defective in regulated protein secretion. To understand the nature of
      this defect, we characterized mutant and wild-type granules. In the absence of
      Grl1p, the sorting of the remaining granule proteins appears normal, and they
      condense to form a well-defined core. However, the condensed cores do not
      demonstrate a visible crystalline lattice, and are notably different from wild
      type in size and shape. The cellular secretion defect arises from failure of the
      aberrant granule cores to undergo rapid expansion and extrusion after exocytic
      fusion of the granule and plasma membranes. The results suggest that sorting,
      condensation, and precise granule assembly are distinct in their requirements for
      Grl1p.

PMID- 8991091
TI  - The sequence NPFXD defines a new class of endocytosis signal in Saccharomyces
      cerevisiae.
AB  - The yeast membrane protein Kex2p uses a tyrosine-containing motif within the
      cytoplasmic domain for localization to a late Golgi compartment. Because Golgi
      membrane proteins mislocalized to the plasma membrane in yeast can undergo
      endocytosis, we examined whether the Golgi localization sequence or other
      sequences in the Kex2p cytoplasmic domain mediate endocytosis. To assess
      endocytic function, the Kex2p cytoplasmic domain was fused to an endocytosis
      defective form of the alpha-factor receptor. Ste2p. Like intact Ste2p, the
      chimeric protein, Stex22p, undergoes rapid endocytosis that is dependent on
      clathrin and End3p. Uptake of Stex22p does not require the Kex2p Golgi
      localization motif. Instead, the sequence NPFSD, located 37 amino acids from the
      COOH terminus, is essential for Stex22p endocytosis. Internalization was
      abolished when the N, P, or F residues were converted to alanine and severely
      impaired upon conversion of D to A. NPFSD restored uptake when added to the COOH
      terminus of an endocytosis-defective Ste2p chimera lacking lysine-based
      endocytosis signals present in wild-type Ste2p. An NPF sequence is present in the
      cytoplasmic domain of the a-factor receptor, Ste3p. Mutation of this sequence
      prevented pheromone-stimulated endocytosis of a truncated form of Ste3p. Our
      results identify NPFSD as a clathrin-dependent endocytosis signal that is
      distinct from the aromatic amino acid-containing Golgi localization motif and
      lysine-based, ubiquitin-dependent endocytosis signals in yeast.

PMID- 8991092
TI  - AP-2-containing clathrin coats assemble on mature lysosomes.
AB  - Coat proteins appear to play a general role in intracellular protein trafficking
      by coordinating a membrane budding event with cargo selection. Here we show that
      the AP-2 adaptor, a clathrin-associated coat-protein complex that nucleates
      clathrin-coated vesicle formation at the cell surface, can also initiate the
      assembly of normal polyhedral clathrin coats on dense lysosomes under
      physiological conditions in vitro. Clathrin coat formation on lysosomes is
      temperature dependent, displays an absolute requirement for ATP, and occurs in
      both semi-intact cells and on purified lysosomes, suggesting that clathrin-coated
      vesicles might regulate retrograde membrane traffic out of the lysosomal
      compartment.

PMID- 8991094
TI  - The initial fusion pore induced by baculovirus GP64 is large and forms quickly.
AB  - The formation of the fusion pore is the first detectable event in membrane fusion
      (Zimmerberg, J., R. Blumenthal, D.P. Sarkar, M. Curran, and S.J. Morris. 1994. J.
      Cell Biol. 127:1885-1894). To date, fusion pores measured in exocytosis and viral
      fusion have shared features that include reversible closure (flickering), highly
      fluctuating semistable stages, and a lag time of at least several seconds between
      the triggering and the pore opening. We investigated baculovirus GP64-induced Sf9
      cell-cell fusion, triggered by external acid solution, using two different
      electrophysiological techniques: double whole-cell recording (for high time
      resolution, model-independent measurements), and the more conventional time
      resolved admittance recordings. Both methods gave essentially the same results,
      thus validating the use of the admittance measurements for fusion pore
      conductance calculations. Fusion was first detected by abrupt pore formation with
      a wide distribution of initial conductance, centered around 1 nS. Often the
      initial fusion pore conductance was stable for many seconds. Fluctuations in
      semistable conductances were much less than those of other fusion pores. The
      waiting time distribution, measured between pH onset and initial pore appearance,
      fits best to a model with many (approximately 19) independent elements. Thus,
      unlike previously measured fusion pores, GP64-mediated pores do not flicker, can
      have large, stable initial pore conductances lasting up to a minute, and have
      typical lag times of < 1 s. These findings are consistent with a barrel-shaped
      model of an initial fusion pore consisting of five to eight GP64 trimers that is
      lined with lipid.

PMID- 8991093
TI  - Centractin (ARP1) associates with spectrin revealing a potential mechanism to
      link dynactin to intracellular organelles.
AB  - Centractin (Arp1), an actin-related protein, is a component of the dynactin
      complex. To investigate potential functions of the protein, we used transient
      transfections to overexpress centractin in mammalian cells. We observed that the
      overexpressed polypeptide formed filamentous structures that were significantly
      longer and more variable in length than those observed in the native dynactin
      complex. The centractin filaments were distinct from conventional actin in
      subunit composition and pharmacology as demonstrated by the absence of
      immunoreactivity of these filaments with an actin-specific antibody, by
      resistance to treatment with the drug cytochalasin D, and by the inability to
      bind phalloidin. We examined the transfected cells for evidence of specific
      associations of the novel centractin filaments with cellular organelles or
      cytoskeletal proteins. Using immunocytochemistry we observed the colocalization
      of Golgi marker proteins with the centractin polymers. Additional
      immunocytochemical analysis using antibodies to non-erythroid spectrin (fodrin)
      and Golgi-spectrin (beta I sigma *) revealed that spectrin colocalized with the
      centractin filaments in transfected cells. Biochemical assays demonstrated that
      spectrin was present in dynactin-enriched cellular fractions, was
      coimmunoprecipitated from rat brain cytosol using antibodies to dynactin
      subunits, and was coeluted with dynactin using affinity chromatography.
      Immunoprecipitations and affinity chromatography also revealed that actin is not
      a bona fide component of dynactin. Our results indicate that spectrin is
      associated with the dynactin complex. We suggest a model in which dynactin
      associates with the Golgi through an interaction between the centractin filament
      of the dynactin complex and a spectrin-linked cytoskeletal network.

PMID- 8991095
TI  - Targeting of Moloney murine leukemia virus gag precursor to the site of virus
      budding.
AB  - Retrovirus Moloney murine leukemia virus (M-MuLV) matures by budding at the cell
      surface. Central to the budding process is the myristoylated viral core protein
      precursor Gag which, even in the absence of all other viral components, is
      capable of associating with the cytoplasmic leaflet of the plasma membrane and
      assembling into extracellular virus-like particles. In this paper we have used
      heterologous, Semliki Forest virus-driven, expression of M-MuLV Gag to study the
      mechanism by which this protein is targeted to the cell surface. In pulse-chase
      experiments, BFA, monensin, and 20 degrees C block did not affect incorporation
      of Gag into extracellular particles thereby indicating that the secretory pathway
      is not involved in targeting of Gag to the cell surface. Subcellular
      fractionation studies demonstrated that newly synthesized Gag became rapidly and
      efficiently associated with membranes which had a density similar to that of
      plasma membrane-derived vesicles. Protease-protection studies confirmed that the
      Gag-containing membranes were of plasma membrane origin, since in crude cell
      homogenates, the bulk of newly synthesized Gag was protease-resistant as expected
      of a protein that binds to the cytoplasmic leaflet of the plasma membrane. Taken
      together these data indicate that targeting of M-MuLV Gag to the cell surface
      proceeds via direct insertion of the protein to the cytoplasmic side of the
      plasma membrane. Furthermore, since the membrane insertion reaction is highly
      efficient and specific, this suggests that the reaction is dependent on as-yet
      unidentified cellular factors.

PMID- 8991096
TI  - The sup-pf-2 mutations of Chlamydomonas alter the activity of the outer dynein
      arms by modification of the gamma-dynein heavy chain.
AB  - The sup-pf-2 mutation is a member of a group of dynein regulatory mutations that
      are capable of restoring motility to paralyzed central pair or radial spoke
      defective strains. Previous work has shown that the flagellar beat frequency is
      reduced in sup-pf-2, but little else was known about the sup-pf-2 phenotype
      (Huang, B., Z. Ramanis, and D.J.L. Luck. 1982. Cell. 28:115-125; Brokaw, C.J.,
      and D.J.L. Luck. 1985. Cell Motil. 5:195-208). We have reexamined sup-pf-2 using
      improved biochemical and structural techniques and by the analysis of additional
      sup-pf-2 alleles. We have found that the sup-pf-2 mutations are associated with
      defects in the outer dynein arms. Biochemical analysis of sup-pf-2-1 axonemes
      indicates that both axonemal ATPase activity and outer arm polypeptides are
      reduced by 40-50% when compared with wild type. By thin-section EM, these defects
      correlate with an approximately 45% loss of outer dynein arm structures.
      Interestingly, this loss is biased toward a subset of outer doublets, resulting
      in a radial asymmetry that may reflect some aspect of outer arm assembly. The
      defects in outer arm assembly do not appear to result from defects in either the
      outer doublet microtubules or the outer arm docking structures, but rather appear
      to result from defects in outer dynein arm components. Analysis of new sup-pf-2
      mutations indicates that the severity of the outer arm assembly defects varies
      with different alleles. Complementation tests and linkage analysis reveal that
      the sup-pf-2 mutations are alleles of the PF28/ODA2 locus, which is thought to
      encode the gamma-dynein heavy chain subunit of the outer arm. The sup-pf-2
      mutations therefore appear to alter the activity of the outer dynein arms by
      modification of the gamma-dynein heavy chain.

PMID- 8991097
TI  - Membrane topology of the high-affinity L-glutamate transporter (GLAST-1) of the
      central nervous system.
AB  - The membrane topology of the high affinity, Na(+)-coupled L-glutamate/L-aspartate
      transporter (GLAST-1) of the central nervous system has been determined.
      Truncated GLAST-1 cDNA constructs encoding protein fragments with an increasing
      number of hydrophobic regions were fused to a cDNA encoding a reporter peptide
      with two N-glycosylation sites. The respective cRNA chimeras were translated in
      vitro and in vivo in Xenopus oocytes. Posttranslational N-glycosylation of the
      two reporter consensus sites monitors the number, size, and orientation of
      membrane-spanning domains. The results of our experiments suggest a novel 10
      transmembrane domain topology of GLAST-1, a representative of the L-glutamate
      neurotransmitter transporter family, with its NH2 and COOH termini on the
      cytoplasmic side, six NH2-terminal hydrophobic transmembrane alpha-helices, and
      four COOH-terminal short hydrophobic domains spanning the bilayer predicted as
      beta-sheets.

PMID- 8991098
TI  - Regulation of epidermal differentiation by a Distal-less homeodomain gene.
AB  - The Distal-less-related homeodomain gene Dlx3 is expressed in terminally
      differentiated murine epidermal cells. Ectopic expression of this gene in the
      basal cell layer of transgenic skin results in a severely abnormal epidermal
      phenotype and leads to perinatal lethality. The basal cells of affected mice
      ceased to proliferate, and expressed the profilaggrin and loricrin genes which
      are normally transcribed only in the latest stages of epidermal differentiation.
      All suprabasal cell types were diminished and the stratum corneum was reduced to
      a single layer. These data indicate that Dlx3 misexpression results in
      transformation of basal cells into more differentiated keratinocytes, suggesting
      that this homeoprotein is an important regulator of epidermal differentiation.

PMID- 8991099
TI  - Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis
      via activation of AP-1 in vitro, and causes growth inhibition in xenografts in
      vivo.
AB  - Human malignant melanoma is notoriously resistant to pharmacological modulation.
      We describe here for the first time that the synthetic retinoid CD437 has a
      strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x
      10(-6) M) via the induction of programmed cell death, as judged by analysis of
      cell morphology, electron microscopical features, and DNA fragmentation.
      Programmed cell death was preceded by a strong activation of the AP-1 complex in
      CD437-treated cells as demonstrated by gel retardation and chloramphenicol
      transferase (CAT) assays. Northern blot analysis showed a time-dependent increase
      in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2
      and p53 mRNA levels remained constant. CD437 also exhibited a strong growth
      inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections
      of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c
      fos overexpressing cells were colocalized by TdT-mediated deoxyuridine
      triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ
      hybridization. Taken together, this report identifies CD437 as a retinoid that
      activates and upregulates the transcription factor AP-1, leading eventually to
      programmed cell death of exposed human melanoma cells in vitro and in vivo.
      Further studies are needed to evaluate whether synthetic retinoids such as CD437
      represent a new class of retinoids, which may open up new ways to a more
      effective therapy of malignant melanoma.

PMID- 8991100
TI  - Quantitative analysis of cadherin-catenin-actin reorganization during development
      of cell-cell adhesion.
AB  - Epithelial cell-cell adhesion requires interactions between opposing
      extracellular domains of E-cadherin, and among the cytoplasmic domain of E
      cadherin, catenins, and actin cytoskeleton. Little is known about how the
      cadherin-catenin-actin complex is assembled upon cell-cell contact, or how these
      complexes initiate and strengthen adhesion. We have used time-lapse differential
      interference contrast (DIC) imaging to observe the development of cell-cell
      contacts, and quantitative retrospective immunocytochemistry to measure
      recruitment of proteins to those contacts. We show that E-cadherin, alpha
      catenin, and beta-catenin, but not plakoglobin, coassemble into Triton X-100
      insoluble (TX-insoluble) structures at cell-cell contacts with kinetics similar
      to those for strengthening of E-cadherin-mediated cell adhesion (Angres, B., A.
      Barth, and W.J. Nelson. 1996. J. Cell Biol. 134:549-557). TX-insoluble E
      cadherin, alpha-catenin, and beta-catenin colocalize along cell-cell contacts in
      spatially discrete micro-domains which we designate "puncta," and the relative
      amounts of each protein in each punctum increase proportionally. As the length of
      the contact increases, the number of puncta increases proportionally along the
      contact and each punctum is associated with a bundle of actin filaments. These
      results indicate that localized clustering of E-cadherin/catenin complexes into
      puncta and their association with actin is involved in initiating cell contacts.
      Subsequently, the spatial ordering of additional puncta along the contact may be
      involved in zippering membranes together, resulting in rapid strengthening of
      adhesion.

PMID- 8991102
TI  - [Family of inhibins and activins: from endocrine to paracrine action].
AB  - Inhibins and activins are structurally-related dimeric proteins mainly produced
      by the gonads (Sertoli cells and granulosa cells) under the stimulation of
      pituitary FSH. Inhibins are 32-kD glycoproteins consisting of an alpha subunit
      and one of two beta subunits (beta A or beta B) leading to inhibin A or B,
      respectively. Activins are made of two beta subunits either identical (activin A
      or B) or not (activin AB). These regulatory peptides are involved in an endocrine
      feedback loop: inhibins decrease and activins stimulate the biosynthesis and
      release of pituitary FSH selectively. Beside their endocrine action that has led
      to the discovery of these peptides, we report main experimental data showing that
      activins and inhibins may act as paracrine and autocrine factors within the
      gonads on an antagonistic mode. Inhibins and activins seem to be involved in the
      regulation of spermatogenesis in males and in follicular maturation in females.
      Potential involvements of inhibins and activins in the pathophysiology of
      reproduction are discussed.

PMID- 8991103
TI  - Exhaustion of blood glucose response and enhancement of insulin response after
      repeated glucagon injections in type-2 diabetes: potentiation by progressive
      hyperglycemia.
AB  - AIMS: To investigate the hyperglycemic and insulinemic response to repeated
      glucagon injections in Type-2 (non-insulin-dependent) diabetic patients. METHODS:
      In overnight fasted Type-2 diabetic patients, three i.v. glucagon (1 mg)
      injections were given as a bolus at two-hour intervals. In the hour preceding
      each glucagon injection, 6 patients received saline and they were tested at near
      baseline blood glucose levels, while 8 patients received a glucose-controlled
      glucose infusion and they were tested at increasing blood glucose levels (7.5 +/-
      0.2, 12.9 +/- 0.5 and 18.7 +/- 0.7 mmol/l). Blood samples were collected at 0, 3,
      5, 10, 15, 30 and 60 min after each glucagon injection. RESULTS: In the patients
      tested at near-baseline blood glucose levels, the blood glucose rise induced by
      glucagon was smaller after repeated injections. By contrast, the B-cell response
      to glucagon was well preserved. In the patients tested at increasing blood
      glucose levels, the blood glucose response to glucagon was abolished after
      repeated injections. By contrast, the B-cell response was significantly
      potentiated. The respective areas under the curve of plasma insulin levels in
      response to glucagon were 563 +/- 72, 1047 +/- 154 and 1844 +/- 305 m U x 30
      min/l (p < 0.001). CONCLUSION: In Type-2 (non-insulin-dependent) diabetic
      patients, repeated glucagon injections, even when administered in a short (4 h)
      period of time, do not exhaust the B-cell. Endogenous insulin secretion is even
      potentiated at increasing blood glucose levels. By contrast, the hyperglycemic
      response to glucagon is significantly abolished, particularly at high blood
      glucose levels.

PMID- 8991101
TI  - Calreticulin modulates cell adhesiveness via regulation of vinculin expression.
AB  - Calreticulin is an ubiquitous and highly conserved high capacity Ca(2+)-binding
      protein that plays a major role in Ca2+ storage within the lumen of the ER. Here,
      using L fibroblast cell lines expressing different levels of calreticulin, we
      show that calreticulin plays a role in the control of cell adhesiveness via
      regulation of expression of vinculin, a cytoskeletal protein essential for cell
      substratum and cell-cell attachments. Both vinculin protein and mRNA levels are
      increased in cells overexpressing calreticulin and are downregulated in cells
      expressing reduced level of calreticulin. Abundance of actin, talin, alpha 5 and
      beta 1 integrins, pp125 focal adhesion kinase, and alpha-catenin is not affected
      by the differential calreticulin expression. Overexpression of calreticulin
      increases both cell-substratum and cell-cell adhesiveness of L fibroblasts that,
      most surprisingly, establish vinculin-rich cell-cell junctions. Upregulation of
      calreticulin also affects adhesion-dependent phenomena such as cell motility
      (which decreases) and cell spreading (which increases). Downregulation of
      calreticulin brings about inverse effects. Cell adhesiveness is Ca2+ regulated.
      The level of calreticulin expression, however, has no effect on either the
      resting cytoplasmic Ca2+ concentration or the magnitude of FGF-induced Ca2+
      transients. Calreticulin, however, participates in Ca2+ homeostasis as its level
      of expression affects cell viability at low concentrations of extracellular Ca2+.
      Consequently, we infer that it is not the Ca2+ storage function of calreticulin
      that affects cell adhesiveness. Neither endogenous calreticulin nor overexpressed
      green fluorescent protein-calreticulin construct can be detected outside of the
      ER. Since all of the adhesion-related effects of differential calreticulin
      expression can be explained by its regulation of vinculin expression, we conclude
      that it is the ER-resident calreticulin that affects cellular adhesiveness.

PMID- 8991104
TI  - [Intracavernous invagination of pituitary macro-adenomas].
AB  - Depending on authors, intra-cavernous invasion by a pituitary adenoma is found in
      9% to 40% of cases. In the light of our own experience, we think that such an
      invasion is probably much less frequent than usually evoked on CT-scan and MRI.
      In our study, it was confirmed in only one case over 125 (0.80%), though
      radiological data suspected an intra-cavernous invasion 17 times. An anatomical
      study on 20 cadavers showed that 30% of normal pituitary glands present with a
      lateral expansion into one or both cavernous sinuses (CS). These natural
      invaginations were already evoked by Harris and Rhoton in 1976. They can resemble
      an intra-cavernous extension or invasion on MRI views, moreover when an adenoma
      increases the volume of this expansion, and in the absence of any rupture of the
      medial wall of the CS. The medial wall of the CS is, in fact, constituted by a
      dural pouch which close-fits the pituitary gland and its expansions; it
      invaginates more or less in the CS, depending on the importance of the pituitary
      lateral expansion. In case of a large adenoma, the finger-glove lateral
      distension of the pouch disappears progressively during the tumoral removal.
      Finally the dura returns to its normal place back, at the end of the procedure.
      This concept of invagination of the CS medial wall, as opposed to that of
      invasion and therefore of rupture of the dural plane, explains the wide range of
      figures concerning the frequency of intracavernous invasion by pituitary
      adenomas, in the literature. These figures are all the more variable as there is
      no absolute criteria of intra-cavernous invasion on CT-scan nor MRI views. In the
      same way, no clinical criteria can be retained to assume the existence of such an
      invasion. So, an ophthalmoplegia seems to be usually linked to a compression of
      occulomotors nerves; it recovers in a large majority of cases, after the adenoma
      is removed. In conclusion we emphasize the necessity of interpreting with great
      care radiological imaging when it evokes' a possible intra-cavernous invasion of
      a pituitary adenoma. The indication of an eventual radiotherapy should be
      retained with as much care as possible, since complete removal of an adenoma and
      its lateral expansion(s) is almost always feasible through a trans-sphenoidal
      route.

PMID- 8991105
TI  - [Diabetes insipidus revealing pituitary metastasis of bronchial carcinoma].
AB  - Pituitary metastasis are rare but represent an important differential diagnosis
      of intrasellar tumorous syndromes. We report one case of intrasellar metastasis
      of a bronchial adenocarcinoma in a 50 year old woman. Clinical syndrome
      associated a tumorous syndrome (cephalalgia, bitemporal hemianopsia) and an
      anterior and posterior hypopituitarism biologically proven. A large intra and
      suprasellar mass which compressed the optic chiasma and highly enhanced after
      gadolinium injection was found by nuclear magnetic resonance imaging. The
      surgical biopsy displayed a pituitary metastasis of a right inferior lobar
      bronchial adenocarcinoma with bone secondary localizations. Cerebral radiotherapy
      and corticotherapy allowed recovery of visual loss but did not prevent rapid
      death. The clinical and radiological features which may evoke an intrasellar
      metastasis were: the tumorous syndrome associated with or revealed by diabetes
      insipidus, loss of spontaneous hypersignal of the neurohypophysis in nuclear
      magnetic resonance imaging, bulking pituitary stalk, bilobar character of the
      mass which is in favour of rapid cell proliferation, postero-superior extension,
      lowering of the V3 floor and very strong and homogeneous signal after gadolinium
      injection.

PMID- 8991106
TI  - [Natural history of dysthyroidism during interferon treatment of chronic
      hepatitis C].
AB  - Thyroid dysfunction developed in 35 patients among a series of 300 (190 men and
      110 women) treated with alpha-interferon (35/300 = 12%. No relationship was
      observed between the type of alpha-interferon, the dose, or hepatic response, but
      there were more women (24/35). Antithyroid antibody levels were frequently
      elevated before treatment (8/35, 23%). Hypothyroidism developed in 27 patients, 7
      with clinical hypothyroidism, 10 with moderate hypothyroidism and 5 with elevated
      TSH only. Patients with severe symptoms and highly elevated thyroid antibodies
      were more prone to develop sustained or irreversible hypothyroidism (10
      patients). Twelve patients recovered a normal thyroid function within a few
      months, but antibody levels fell more slowly. Primary hyperthyroidism of variable
      severity appeared in 13 patients. In 8 patients, normal thyroid function was
      recovered within a few weeks but thyroid antibodies remained high for at least
      one year. In 5 others spontaneous hypothyroidism occurred within a few weeks
      ("biphasic" hypothyroidism). Direct toxicity appears to be less probable than an
      autoimmune mechanism; elevated antithyroid antibodies were observed in only 20
      patients (57%). In clinical practice, TSH levels should be regularly monitored
      during and after alpha-interferon therapy.

PMID- 8991107
TI  - [Presence of ophthalmopathy in all cases of Basedow disease?].
AB  - In order to evaluate the frequency of ophthalmopathy in Graves' disease, we used
      a progression criterion, the variation of the eyeball protrusion, in a group of
      145 patients initially examined at the time when thyrotoxicosis was diagnosed,
      before any treatment. By the means of a systematic measure of the protrusion with
      the Hertel's exophthalmometer at every consultation, we calculated for each
      patient the variation of protrusion (delta PO) between each annual mean value and
      the initial value. The mean survey was 6.4 years (range 1-18 years). For the
      whole group, we observed, after a slight increase (0.3 mm) during the first year,
      a progressive decrease, which reached about 4 mm at the 12th year and kept an
      afterwards (p < 0.01 at 3 years; p < 0.001 afterwards). The percentage of cases
      in which the decrease was significant related to the initial value (> or = 2 mm)
      rose regularly to reach 100% at the 16th year. These results seem to give
      evidence of the constant nature of ophthalmopathy at the initial stage of Graves'
      hyperthyroidism.

PMID- 8991109
TI  - [Chemodectoma secreting carotid glomus: characteristics and contribution of
      magnetic resonance imaging. Apropos of 2 cases].
AB  - Two cases of carotid glomus chemodectomas with production of catecholamines are
      reported. The place of chemodectomas among the neuroendocrine tumors called
      paragangliomas is recalled. Chemodectomas only very infrequently produce
      catecholamines (1 to 10%). Magnetic resonance imaging is superior to computerized
      tomography and metaiodobeuzylguanidine scintigraphy in the detection and the
      characterization of adrenal and extra-adrenal functioning paragangliomas of the
      orthosympathic system. Few data are available for the imaging of functioning
      parasympathetic paragangliomas (chemodectomas). The two case reports illustrate
      the contribution of the magnetic resonance imaging in the detection and the
      characterization of chemodectomas.

PMID- 8991108
TI  - [Fine needle puncture--method of treatment in nodular pathology of the thyroid].
AB  - Fine needle biopsy (FNB) has been used as a therapeutic method in different
      nodular lesions of the thyroid. Between 1989-1995, 295 subjects with thyroid
      cysts, 235 women and 60 men have been treated by FNB. The treatment of cysts was
      performed by: one or multiple aspirations in 207 cases, sclerosis by injection
      with tetracycline in 77 cases and by ethanol washing in 11 cases. 263 (89.11%)
      cases have been cured and we have lost track of 32 cases in the survey. Of the
      207 cases treated by aspiration, 177 (86.5%) have been cured after one or more
      aspirations. Of the 77 cases treated by injections with tetracycline, 75 (97.26%)
      displayed sclerosis after one or more injections. All 11 cases treated by ethanol
      washing method displayed sclerosis. Between 1993-1995 we used percutaneous
      ethanol injection (PE1) in 6 cases, as an alternative to the classic treatment,
      in order to induce necrosis of toxic adenoma. After 1 to 9 injections all cases
      were cured, with the appearance of the entire image of the gland on the
      scintigram. In 4 cases of cold nodules with benign cytology PEI, induced a
      significant decrease of volume appreciated by sonography.

PMID- 8991110
TI  - [Pituitary enlargement in congenital adrenal hyperplasia].
AB  - The aim of the suppression of pituitary adrenal axis in the management of
      patients with congenital adrenal hyperplasia is to reduce the hypersecretion of
      adrenal androgens. However, the local consequences of the hyperreactivity of
      corticotropin cells during inadequate therapy is not well defined. In this case
      report, we present the observation of a 28-year-old patient with congenital
      adrenal hyperplasia with inadequate treatment in whom a pituitary enlargement was
      detected after MR imaging for headaches. This observation underlines the need for
      a pituitary follow-up in these specific patients.

PMID- 8991111
TI  - [Cardiac tamponade revealing hypothyroidism].

PMID- 8991112
TI  - [European perspectives of the training of endocrinologists].

PMID- 8991113
TI  - The medium cell sIg+, proplasmocytic lymphoma/leukemia. Positive and differential
      diagnosis with other B-lymphoblastoid neoplasias.
AB  - The authors describe the neoplasia of the only cell of the B-lymphocytic
      differentiation step, of which no lymphoma has yet been described: the cell
      intermediary between the memory B cell of the mantle zone, and the long-lived,
      marrow migrating and IgD or IgG secreting plasma cell, or mucosae migrating IgA
      secreting plasma-cell: they describe its neoplasia under the name of "medium cell
      cmu- sIg+ proplasmocytic lymphoma". It is defined by four characters: a) the
      homogeneous medium sized lymphoblastoid cells with one nucleolus per cell; b) the
      cmu- sIg+ marker as well as the CD38 and CD22; c) the t(11;14) translocation; and
      d) the poor prognosis and rapidly fatal evolution with a rapid conversion to the
      leukemic phase. The latter has probably been described, when the diagnosis is
      only made at this stage, as "B-prolymphocytic leukemia", which is nonsense, as
      the pre B-cells are cmu+ sIg-.

PMID- 8991114
TI  - Treatment of small non-cleaved cell lymphoma in the adult.
AB  - Small non-cleaved cell lymphoma is one of the most rapidly growing malignancies
      and in children is highly curable. However, in adults, the disease is
      disseminated in approximately one half of the patients, and with standard
      chemotherapy used for lymphoma, is less curable than it is in children,
      especially in patients presenting with bone marrow involvement. However, recent
      developments in clinical management using intensive dose therapy for this disease
      have improved the eventual outcome for these patients. This review focuses on
      some of these improvements.

PMID- 8991115
TI  - Autologous bone marrow transplantation in chronic lymphocytic leukemia (CLL).
AB  - Chronic lymphocytic leukemia (CLL) is an indolent disease characterized by an
      abnormal proliferation of monoclonal lymphocytes in the bone marrow and lymphoid
      tissues. Most of the cases (> 90%) belong to the B-lymphocyte lineage and the
      course of the disease is variable depending on the presence of poor prognostic
      factors at diagnosis. Therefore optimal treatment is still questioned; presently
      there are no proven cures for CLL, but the natural history of the disease and the
      advanced age of the majority of patients makes prolongation of survival a
      reasonable therapeutic goal in most cases. The traditional therapeutic approach
      has been based on the activity of alkylating agents and corticosteroid, while
      patients resistant have been treated with nucleoside analogs. However, patients
      ultimately relapse and the choice of salvage therapy by conventional methods does
      not offer many chances. Particularly in younger patients, with poor prognostic
      factors, the therapeutic options may substantially change in the near future,
      based on alternative and innovative approaches aimed at achieving cure or long
      disease-free-survival. The results of high-dose therapy followed by reinfusion of
      hematopoietic stem cells, either from bone marrow or peripheral blood, will be
      presented and discussed.

PMID- 8991116
TI  - Treatment of Burkitt's lymphoma in HIV-positive patients.
AB  - Many Burkitt's-type non-Hodgkin lymphomas (NHL) in patients without HIV infection
      are curable with current brief high-dose combination chemotherapy regimens.
      Burkitt's-type lymphomas (BL) comprise 30-40% of HIV-associated NHL. Their
      morphologic, clinical, cytogenetic and molecular genetic characteristics are
      similar to those of sporadic BL unassociated with HIV infection. They often occur
      in less immunosuppressed HIV-infected individuals than the other types of NHL.
      Most patients with HIV-associated NHL benefit as much from low-dose as from
      standard or high-dose chemotherapy with less toxicity. However, there may be a
      subpopulation of HIV-infected patients with Burkitt's-type NHL and well preserved
      immune status who may benefit from high-dose chemotherapy programs that are
      effective for BL patients without HIV infection.

PMID- 8991117
TI  - Minimal residual disease in non-Hodgkin's lymphoma.
AB  - Recent advances in the sensitivity of detection methods have clearly illustrated
      that patients in complete clinical remission often harbor residual lymphoma cells
      that are below the limit of detection using standard staging techniques. However,
      the clinical significance of this detection is by no means clear. Patients have
      been identified who remain in very long-term clinical remission despite detection
      of residual lymphoma cells. In contrast, the eradication of lymphoma is
      associated with improved outcome in patients undergoing autologous bone marrow
      transplantation. We review the methodologies for the detection of minimal
      residual lymphoma and discusses the clinical significance of this detection.

PMID- 8991118
TI  - The association of the Epstein-Barr virus with malignant lymphoma.
AB  - The Epstein-Barr virus, a human herpesvirus, has been found in the neoplastic
      cells of numerous lymphoid malignancies, including Burkitt's lymphoma,
      immunodeficiency-associated lymphoproliferative disorders, nasal T/NK lymphoma,
      and Hodgkin's disease. The available data suggest that Epstein-Barr virus
      contributes to the pathogenesis of many of these neoplasms but is not directly
      linked to the etiology of any of these lymphomas.

PMID- 8991139
TI  - [Antiphospholipid antibodies: limitations and potential use in liver diseases].

PMID- 8991140
TI  - [Should healthy carriers of HBs antigen be followed-up?].

PMID- 8991141
TI  - [Course of the recurrence of hepatitis C virus infection after liver
      transplantation].
AB  - OBJECTIVES: Hepatitis C virus recurrence is frequent after orthotopic liver
      transplantation. The aim of this study was to evaluate the clinical, biological,
      and histological characteristics of recurrence. METHODS: One hundred and ten
      patients (91 males, mean age 49 years) with liver transplantation were followed
      up for more than 1 year (mean: 26 months, range: 12-71). Hepatitis C virus
      serologic 2nd generation tests were performed before and every 3 months after
      transplantation in all patients. Serum RNA was detected every 6 months after
      transplantation by polymerase chain reaction. A percutaneous liver biopsy was
      performed every year in all patients and in case of abnormal biological liver
      tests. RESULTS: In 44 patients (40%), hepatitis C virus serology was positive
      before transplantation, and was unchanged after transplantation. In this group
      histologic chronic hepatitis was observed in 35 patients (79.5%). The mean
      Knodell score was 8.4 +/- 2.3, associated with an increase in serum
      aminotransferases (> twice the upper limit of normal) in 26 cases (74.3%) and
      with serum RNA in 33 cases (94.3%). The Knodell score was not significantly
      higher 2 years or more after transplantation than before (9.5 +/- 3.9 vs 7.2 +/-
      3.5). In 66 patients with negative hepatitis C virus serology before
      transplantation, no changes were noted after transplantation. In this group,
      histologic chronic hepatitis was found in 14 cases (21.2%) associated with serum
      hepatitis C virus RNA in 7 cases. Actuarial survival rates of the two groups were
      97.1% and 91.2% at 2 years, and 93.5% and 86.7% at 5 years, respectively. No
      death clearly related to hepatitis C virus recurrence was observed. CONCLUSION:
      Hepatitis C virus recurrence after liver transplantation is frequently associated
      with chronic hepatitis, and a progressive increase in liver lesions.
      Nevertheless, the 5-year survival rates was not different in these patients
      compared to patients with negative hepatitis C virus serology before
      transplantation.

PMID- 8991142
TI  - [Serum cardiolipin antibodies in patients with alcoholic cirrhosis].
AB  - OBJECTIVE: Although portal obstruction is a complication in cirrhosis which is
      usually associated with hepatocellular carcinoma, its precise neoplastic or
      thrombotic nature is not easy to determine. Serum antiphospholipid antibodies
      could be involved in thrombosis-related portal obstruction. PATIENTS AND METHODS:
      The presence of serum anticardiolipid antibodies was investigated by an
      immunoenzymatic technique in 129 patients with alcoholic cirrhosis, 47 patients
      with hepatocellular carcinoma with (n = 18) or without (n = 29) portal
      obstruction, and 82 patients without hepatocellular carcinoma or portal
      obstruction. Five control groups were included: patients with non alcoholic
      cirrhosis (n = 21), non cirrhotic alcoholic liver disease (n = 21), chronic viral
      hepatitis (n = 14), extra-hepatic cholestasis (n = 9), and hypergammaglobulinemia
      associated with human immunodeficiency virus infection without liver disease (n =
      28). RESULTS: The prevalence of serum anticardiolipid antibodies was 57% in
      patients with alcoholic cirrhosis, which was significantly different from the
      prevalence in the control groups which ranged from 0 to 32%. Anticardiolipid
      antibodies were of IgA isotypes in 90.5% of the cases, mainly related to the
      degree of liver failure but not to hepatocellular carcinoma or portal
      obstruction. CONCLUSION: In alcoholic cirrhosis, serum anticardiolipid antibodies
      do not seem to be related to the pathogenesis of portal obstruction in patients
      with hepatocellular carcinoma. They could rather reflect liver lesions and
      immunological dysfunctions.

PMID- 8991143
TI  - [Hepatotoxicity of drugs. 9th update of the bibliographic database of hepatic
      involvements and related drugs].

PMID- 8991144
TI  - [Microscopic colitis (collagenous colitis, lymphocytic colitis and other forms):
      a unifying nosological concept].

PMID- 8991145
TI  - [Functional diarrheas are not, in most cases, minor clinical forms of lymphocytic
      or collagenous colitis].
AB  - AIM: The aim of the study was to test the hypothesis that some patients with
      functional diarrhea could actually suffer from a mild clinical pattern of
      collagenous or lymphocytic colitis. PATIENTS AND METHODS: Twenty consecutive
      patients with chronic diarrhea were included in the study if the colonic mucosa
      appeared normal during colonoscopy. From multiple colonic biopsies were
      established a conventional histological diagnosis and a quantitative histological
      diagnosis. This latter diagnosis was based on the semiquantitative evaluation of
      epithelial morphological alterations and lamina propria monocellular
      infiltration, and on the determination of both intraepithelial lymphocyte count
      and subepithelial collagen layer thickness. Multiple colonic biopsies from 12
      control patients without diarrhea were analyzed according to the same protocol.
      RESULTS: Among the 20 patients with diarrhea, the quantitative diagnosis of
      collagenous colitis was made in 3 patients (thickness of the collagen band
      between 11 and 26 microns) and the diagnosis of lymphocytic colitis in one (21%
      of intraepithelial lymphocytes). The percentage of intraepithelial lymphocytes
      did not differ between the 16 remaining patients and the controls (12 +/- 5% and
      9 +/- 4%, respectively). Similarly, the score of surface epithelial damage and
      the score of lamina propria infiltration in patients with diarrhea (1.2 +/- 1.0
      et 1.7 +/- 1.5) were not different from the values in the control group (1.3 +/-
      1.3 et 1.5 +/- 1.2). The mean fecal weight in patients with diarrhea but without
      colitis was 161 +/- 130 g/d. All the values of fecal weight were below 300 g/d,
      except in one patient with a past history of truncular vagotomy. CONCLUSIONS:
      These results suggest that most of the patients with functional diarrhea do not
      suffer from mild clinical patterns of collagenous or lymphocytic colitis.

PMID- 8991146
TI  - [Palliative treatment of esophageal neoplastic stenosis using bipolar
      electrocoagulation probe].
AB  - OBJECTIVE, PATIENTS AND METHODS: The objective of this study was to evaluate the
      results of palliative bipolar electrocoagulation probe (BICAP) treatment in 26
      patients with non surgical, obstructive esophageal cancer. The mean tumor length
      was 7.2 cm. The strictures were located as follows: 3 in the cervical esophagus,
      8 in the thoracic esophagus, 13 in the distal third of the esophagus and 2
      involved both the cervical and thoracic esophagus. Most lesions were
      circumferential (73% versus 27% non circumferential) and exophytic (78% versus
      22% sub mucosal). Coagulation was carried out under direct endoscopic control in
      the forward direction. The success of treatment was evaluated on the basis of the
      degree of reopening achieved (easy passage of an endoscope 12 mm in diameter) and
      good functional results (improvement of dysphagia, scored from 0 to 4 using a
      standard grading scale, for more than 15 days). RESULTS: Twenty-six patients
      underwent a total of 45 BICAP treatments (31 initial sessions, 14 repeated
      sessions). Reopening was achieved in 92% of cases and good functional results
      were obtained in 85% (mean dysphagia score: 3.2 before treatment versus 1.1 after
      treatment). The improvement of dysphagia resulted in a significant improvement of
      general performance status and stabilization or weight improvement in 21
      patients. The mean number of sessions necessary for good initial results was 1.2
      +/- 0.4. After the initial treatment by BICAP, radiotherapy or radiochemotherapy
      were respectively associated in 4 and 10 patients. The median duration of
      improvement was significantly longer in patients who underwent radiochemotherapy
      as compared with patients treated by BICAP alone (22 weeks versus 4 weeks).
      During the follow-up, 9 patients required several BICAP treatments and at the end
      of their disease, 12 patients underwent other palliative procedures. Major
      complications occurred in 4 cases (2 esotracheal fistulas, 1 hemorrhage, and 1
      aspiration pneumonia) and mortality related to the procedure was 8%. CONCLUSIONS:
      Palliative BICAP treatment of obstructing esophageal and cardial cancer provide
      quick relief of dysphagia but repeated treatment sessions are necessary to
      maintain initial improvement. The procedure requires a short hospitalization stay
      and can be easily accomplished in all cases regardless of the tumor features.

PMID- 8991147
TI  - [Effects of preoperative artificial nutrition in intestinal resections for Crohn
      disease].
AB  - Artificial nutrition prior to bowel resection has not been evaluated fully. The
      aim of the present study was to assess the effects of preoperative artificial
      nutrition upon postoperative complications, length of resected bowel and relapses
      of Crohn disease. RESULTS: Between 1990 and 1994, 108 consecutive patients
      underwent bowel resection for Crohn disease. Thirty nine patients had received
      exclusive enteral nutrition (n = 14) or parenteral nutrition (n = 25) for 19 +/-
      10 days. Patients who had received artificial nutrition were more malnourished
      and had complicated Crohn disease (fistulae, abscesses) more often than patients
      operated without artificial nutrition. After 19 days of artificial nutrition, the
      nutritional state of patients was not significantly improved. Postoperative
      complication rate was higher in patients operated after artificial nutrition (33
      vs. 16%; P = 0.03). Using multivariate prognosis analysis, the extent of colic
      resection was significantly associated with postoperative complications (P =
      0.0003). Length of resected bowel and relapse rates were similar in patients with
      or without preoperative nutrition. CONCLUSION: Artificial nutrition prior to
      bowel resection for Crohn's disease is indicated in patients with the most severe
      form of the disease. A preoperative nutrition of 19 days does not seem to reduce
      postoperative complications nor the length of resected bowel.

PMID- 8991148
TI  - [Adjuvant therapy of cancer of the rectum].

PMID- 8991149
TI  - [Lower digestive endoscopies. Recommendations and medical references. Agence
      Nationale pour le Developpement de l'Evaluation Medicale].

PMID- 8991150
TI  - [Portal thrombosis disclosing antiphospholipid syndrome. 2 cases].
AB  - The presence of serum antiphospholipid antibodies is associated with arterial and
      venous thrombosis. We report two cases of portal vein thrombosis associated with
      serum antiphospholipid antibodies. In our two patients, systemic lupus
      erythematosus, chronic liver disease, hepatocellular carcinoma,
      myeloproliferative disorders and coagulation inhibitor deficiency were excluded
      after extensive tests were performed to diagnose portal vein thrombosis and after
      a follow-up period of 6 and 7 years, respectively. The test for serum
      antiphospholipid antibodies was positive on two occasions in both patients. Both
      patients were treated with endoscopic sclerotherapy for bleeding esophageal
      varices and with long term anticoagulant therapy for the prevention of recurrent
      thrombosis. These two cases suggest that serum antiphospholipid antibodies should
      be investigated in patients with portal vein thrombosis of unexplained etiology.

PMID- 8991151
TI  - [Nodular regenerative hyperplasia associated with primary antiphospholipid
      syndrome].
AB  - Nodular regenerative hyperplasia of the liver is characterized by diffuse
      nodularity of the hepatic parenchyma without fibrotic septa. It may be related to
      venous or arterial obstruction in the portal tract. We report a case of primary
      antiphospholipid syndrome associated with nodular regenerative hyperplasia in a
      45-year old woman. The patient had an ischemic stroke, associated with an acute
      arterial ischemia of the left leg. She had high titers of serum anticardiolipin
      antibodies. Nodular regenerative hyperplasia of the liver was histologically
      confirmed and was associated with anicteric cholestasis. This case provides
      additional evidence that a thrombotic mechanism may play a role in the
      pathogenesis of nodular regenerative hyperplasia of the liver.

PMID- 8991152
TI  - [Mesenteric panniculitis simulating Crohn disease].
AB  - Mesenteric panniculitis is a rare disease involving the adipose tissue of the
      mesentery. We report a case of a 27-year-old woman with mesenteric panniculitis,
      who presented clinical and radiological features mimicking Crohn's disease. In
      the outcome, she presented a small bowel perforation, unusual in this pathology,
      and an annexial involvement. This case reminds us of the role of sepsis and
      repeated abdominal surgery in relation to the pathogenesis of mesenteric
      panniculitis. We report the first case of mesenteric panniculitis mimicking
      Crohn's disease.

PMID- 8991153
TI  - [Toxocariasis and functional intestinal disorders. Presentation of 4 cases].
AB  - We report 4 cases of adults patients, suffering from irritable bowel syndrome,
      which had been attributed late to toxocariasis and for whom the treatment led to
      recovery. Hypereosinophilia was present only in 3 cases. These cases show that
      toxocariasis is not limited anymore to its two classical expressions: visceral
      larva migrans and ocular toxocariasis. So it is useful to think of it to confirm
      and treat it in the case of patients suffering from irritable bowel syndrome.
      This enables shorter diagnosis delay (14 months in average for our patients) and
      this is essential for therapeutic efficiency.

PMID- 8991154
TI  - [Hepatic tuberculosis of pseudotumor form in an immunocompetent patient. Clinical
      and radiological aspect].

PMID- 8991155
TI  - [Fatal sub-fulminant hepatitis caused by cyproterone acetate. A new case].

PMID- 8991156
TI  - [Lymphocytic colitis and Cyclo 3 fort: 4 new cases].

PMID- 8991158
TI  - Epithelial apoptosis as a very early marker of drug-induced colitis: the example
      of ranitidine.

PMID- 8991157
TI  - [Hemorrhagic rectocolitis in a cardiac transplant recipient under long-term
      cyclosporine].

PMID- 8991159
TI  - [Rupture of cystic dystrophy ina case of aberrant pancreas following upper
      digestive endoscopy].

PMID- 8991160
TI  - [The acromio-humeral interval. A study of the factors influencing its height].
AB  - PURPOSE OF THE STUDY: The narrowing of the Acromio Humeral Interval (AHI) under 6
      7 mm, lower limit reported in normal shoulder, has been considered to be a
      specific indicator for full-thickness cuff tears. The purpose of this study was
      to analyse the factors influencing the AHI. METHODS: 264 shoulders were operated
      on between 1984 and 1994 for full thickness tear of the supraspinatus and
      infraspinatus associated or not with an anterior cuff lesion. All patients had X
      ray with A.P. view of the shoulder in neutral rotation. The AHI was defined as
      the shortest distance measured between the inferior cortex (dense line) of the
      acromion and the humerus. CT arthrogram was performed in 84 patients to analyse
      cuff muscular fatty degeneration. A full thickness tear was confirmed and
      measured by surgical approach in all cases. RESULTS: There was a moderate
      significant relationship (p < 0.05) between AHI and symptoms duration. There was
      a significant relationship between AHI and tear size (p < 0.05). When the
      supraspinatus tendon was only torn, the mean AHI was 9.5 +/- 0.17 mm (4.5 per
      cent of narrowing AHI). When supra and infraspinatus tendon were torn, the mean
      AHI was 7.5 +/- 0.4 mm (28 per cent of narrow AHI) and when an anterior lesion
      was associated, the mean AHI decreased to 5.4 +/- 0.5 mm and the percentage of
      narrow AHI increased to 63 per cent. The AHI was not influenced by the biceps
      rupture: with a similar symptoms duration, the mean AHI was 9 +/- 0.5 mm with
      biceps tear versus 9.2 +/- 2 mm when the biceps was normal. However, the mean AHI
      decreased to 5.5 +/- 0.6 mm when the long head of the biceps was dislocated and
      the AHI was less than 7 mm in 61 per cent of the cases. A highly significant
      relationship was found between the AHI and the infraspinatus muscle degeneration.
      We have found 100 per cent incidence of AHI narrowing when the infraspinatus was
      degenerated (mean AHI 2.2 +/- 1.1 mm). A moderate similar relationship was found
      concerning the supraspinatus muscle (p < 0.05) and no relationship was found with
      the subscapularis degeneration. DISCUSSION: The infraspinatus, external rotator
      of the humerus, seems to be the major active depressor of the humeral head. The
      biceps tendon, which is a passive depressor of the humerus, has no influence on
      the AHI whatever it is ruptured or not. However biceps dislocation is associated
      with significant humeral head superior migration. Symptoms duration and cuff tear
      size seem to be only secondary factors affecting the AHI. CONCLUSION: AHI
      narrowing should evocate a severe cuff tear with biceps dislocation or muscular
      degeneration. In these cases, surgical repair might be questionable. AHI value is
      more prognostic than diagnostic.

PMID- 8991161
TI  - [Arthrodesis of the shoulder for post-traumatic palsy of the brachial plexus.
      Analysis of a series of 18 cases].
AB  - PURPOSE OF THE STUDY: In case of severe traction injuries of the supraclavicular
      brachial plexus in adult, the functional results of direct shoulder nerve repair
      are less predictable than those of the elbow. Furthermore, the surgical
      management of the remaining flail shoulder is still controversial. The post
      operative results and the indication for shoulder arthrodesis are evaluated in
      this study. MATERIAL AND METHODS: Between October 1978 and January 1994, 18 gleno
      humeral arthrodesis were performed on 18 patients for paralytic shoulder
      following brachial plexus injury. The average age at the time of operation was 25
      years. A C5C6 lesion was present in 2 patients, a C5C6C7 lesion in 8 patients and
      a C5 to T1 lesion in the remaining 8 patients. Seven patients had a suprascapular
      nerve reinnervation failure. All these 18 patients recovered an active elbow
      flexion spontaneously or following direct nerve repair, tendon or free muscle
      transfer. The average delay between nerve repair and arthrodesis was 2 years and
      4 months. For fixation, we always used internal fixation by screws, combined to
      an external fixator device in 10 cases. RESULTS: 16 patients were reviewed with
      an average follow-up of 6 years and 10 months (min. 6 months, max. 15 years and 8
      months). Two types of complications occurred: 2 cases of gleno-humeral non-union
      requiring revision with bone-grafting, and 3 humeral fractures in the first 6
      months after arthrodesis. The study of the arthrodesis position showed an average
      abduction of 25 degrees, an average flexion of 18 degrees, an average internal
      rotation of 22 degrees. The average motion values are 60 degrees of abduction and
      flexion, 14 degrees of extension, 0 degree of external rotation and 48 degrees of
      internal rotation. The range of motion depends closely on scapulo-thoracic
      muscles strength, especially the serratus anterior muscle. A flail hand primarily
      influences the subjective result. 14 of the 16 patients could easily reach their
      mouth. The average muscle shoulder strength, evaluated with the Isobex device, is
      11 kg for flexion and abduction, 9 kg for adduction, 8 kg for internal rotation
      and 4 kg for external rotation. DISCUSSION AND CONCLUSION: Gleno-humeral
      arthrodesis is a reliable method for restoring shoulder function in case of
      brachial plexus sequellae lesion, giving more strength, but less external
      rotation than shoulder nerve repair.

PMID- 8991162
TI  - [Fractures of the distal radius with dorsal displacement: a comparative study of
      the predictive value of 6 classifications].
AB  - PURPOSE OF THE STUDY: The authors compare six classifications in a prospective
      study of distal radius fractures surgical treatment. Classifications included
      Castaing's, Frykman's, Gartland's, Older's, Lindstrom's and Jenkins'. MATERIAL:
      96 patients presenting a distal radius fracture were included in a protocol
      comparing two surgical treatments. 42 were treated with styloid pinning and
      immobilization while 54 with intra-focal pinning and immediate mobilization
      according to Kapandji's technique. METHODS: Each patient was graded initially
      according to each six classifications. Patients were reviewed at 6 weeks, 3, 6,
      12, and 24 months. Clinical and radiographical evaluation were performed.
      Clinical and radiological results were compared according to each group of
      classification. RESULTS: None of the six classifications appeared to have any
      utility to predict functional or radiological results. None was able to
      distinguish treatment option. DISCUSSION: The six classifications did not permit
      to predict clinical or radiological outcome of distal radius fractures treated by
      radial styloid pinning or Kapandji's technique. All those classifications have
      been described for conservative treatment rarely performed in France for
      displaced fractures. CONCLUSION: The six classifications tested showed no
      predictive value in K-wire treatment of dorsally displaced distal radius
      fractures.

PMID- 8991163
TI  - [Hip in arthrogryposis multiplex congenita].
AB  - PURPOSE OF THE STUDY: In arthrogryposis Multiplex Congenita (AMC) multiple joint
      contractures and deformities are present. Hips are often affected. In this follow
      up study the outcome after primary treatment and secondary surgical procedures
      was analyzed with clinical and radiological features. MATERIAL AND METHODS: 52
      patients with AMC were treated at Children's Hospital, Helsinki. 34 patients had
      Hip joint involvement. The most common type of Hip joint involvement was a
      flexion contracture (40 per cent). Thirty-five per cent of patients had rigid
      dislocations. Ten hips with rigid dislocations and four hips with flexion
      contractures was primarily operated on. Two failures of the primary operative
      procedures were noted. Thirty-one dislocated hips were treated non-operatively.
      RESULTS: In fourteen cases, reduction could not be achieved. Nineteen delayed
      surgical procedures were done. Acetabuloplasty was made in 6 hips, femoral
      osteotomy in 8 hips and total hip replacement in 3 hips. Aseptic necrosis of the
      femoral head encountered for 4 poor results in two cases of acetabuloplasty and 3
      hips had a poor range of motion. In flexion contractures of the hips, 6
      corrective osteotomies were done and in four cases the results were good. In all
      cases of total hip replacement the results were good and no complications were
      seen. DISCUSSION: The inefficiency to achieve reduction of dislocated hips in AMC
      patients by conservative methods was confirmed in this study. Although it has
      been claimed that the majority of patients with flexion contractures can be
      managed by conservative treatment there were ten patients in this series who did
      not respond to this form of treatment. CONCLUSION: The primary form of treatment
      should be operative. Only in selected cases with bilateral dislocations should it
      be considered to leave the hips untreated. Double femoral osteotomy in recurrent
      flexion contractures or resistant flexion contractures and total hip replacement
      in adult patients with hip dislocations are useful methods.

PMID- 8991164
TI  - [The Staca nail-plate in the treatment of trochanteric fractures].
AB  - PURPOSE OF THE STUDY: The Staca nail-plate (SNP) is 32 years old. This implant
      was created by Descamp and Kerner from Nice in 1964. This study evaluates the
      experience with the SNP in two Orthopaedic Departments from Metz and Nancy
      Regional Hospitals, between January 1989 and July 1991. MATERIAL AND METHODS:
      This is a clinical and radiological retrospective study. Out of the 175 patients,
      152 were reviewed at 3 months and 127 at more than 9 months. The radiological
      assessment was made by measuring the post-operative cervical angle, the position
      of the nail within the femoral neck, the inter-fragmentary distance and the
      distance between nail and femoral head cartilage. 175 trochanteric fractures (119
      women and 56 men) had osteosynthesis with the SNP. The mean age was 79 years
      (range: 36 to 96 years). Only 29 patients were free of general associated
      pathology. The fracture was always traumatic. The right femur was involved in 97
      cases. Following the Ender classification there were 87 stable and 88 unstable
      fractures (59 complex pertrochanteric, 19 inter and sub-trochanteric and
      trochantero-diaphyseal). RESULTS: Post-operative reduction was anatomical in 66
      per cent and satisfactory in 89 per cent of cases. In three cases there was an
      acetabular protrusion of the nail, in two cases there was a varus reduction and
      fixation and in six cases the plate was not fitting correctly the diaphysis. The
      average per-operative blood-loss was 300 cc. There was one per-operative death
      and eight early post-operative deaths. Sitting was allowed 24 hrs, after surgery
      in 94 per cent of patients. 68 per cent of patients started walking within the
      first 15 days after surgery. There were 37 per cent general complications, mainly
      respiratory and urinary infections, but also 2 deep-vein phlebitis, with
      pulmonary embolism and death. 17 post-operative hematoma were noted, out of which
      two required surgery. The general mortality reached 15 per cent in three months
      and 22 per cent in nine months. 70 per cent of the patients were free of pain at
      3 months and 78 per cent at 9 months, 65 per cent being able to walk without
      crutches. Nail acetabular protrusion was observed in 16 cases (3 in early post
      operative period, 8 within three months and 2 between the third and the ninth
      month). The protrusion was related to the nail positioning in 11 out of the 16
      cases. This complication required SNP removal in 7 cases, replacement of the SNP
      in 3 cases and total hip arthroplasty in two cases. Correct nail length
      assessment is the important step in order to avoid protrusion and has to take
      into account the interfragmentary distance after reduction (if any). A good per
      operative nail impaction is mandatory. CONCLUSION: Compared to other implants
      (THS, DHS, Gamma-nail, Ender), the SNP gives comparable results and a stable
      fixation. The SNP is a reliable implant. The most common complication in our
      series is protrusion which required reintervention in 6.8 per cent of the cases.
      Currently we avoid this complication by a good per-operative nail impaction.

PMID- 8991165
TI  - [Fractures of the anterior rim of the distal part of the tibia. Apropos of a
      series of 38 cases].
AB  - PURPOSE OF THE STUDY: Fracture of the anterior rim of the distal tibia is a rare
      injury. This fracture seems less serious than other pilon fractures but its
      treatment is often difficult and didn't give better results. The aim of this
      study was to describe problem we dealed with and to suggest solutions in order to
      improve long term results. MATERIAL: The study included 38 cases, treated in 5
      Paris district trauma centers, with a minimal follow-up of 6 months. All patients
      were asked for clinical and radiological review between september 92 and march 93
      ; otherwise, latest review datas were used. METHODS: Authors suggest a
      radiological classification based upon type, width and talus anterior
      displacement. Different surgical procedures were performed for 33 cases (screw,
      plate, external fixation) ; conservative treatment was used 5 times (non weight
      bearing plaster cast). Anatomical reconstruction was analysed. Functional results
      scoring system included pain, global abilities and ankle range of motion. Ankle
      arthritis was rated according to 1992 SOFCOT scoring system at 1 and 3 year
      follow-up. RESULTS: Follow-up ranges from 6 months to 11 years (average 28
      months). 55 per cent of cases were lost for review with 1 year mean follow-up. 45
      per cent of patients were recently tested with 4 year mean follow-up. Three
      ankles had joint fusion 6 to 18 months after trauma. Functional result was poor.
      For 35 ankles analysed 1 out of 4 remained totally painless (9 cases), 1 out of 2
      had a good function (20 cases) and 1 out of 3 normal X-rays (12 cases). Arthritis
      was found for 2 ankles out of 3 after one year follow-up (16 cases out of 23).
      Loss of reduction or incomplete reconstruction seemed the most important point
      (13 cases out 38, 13 cases after 35 surgical procedures). DISCUSSION: Many
      patients didn't get a long term evaluation, and this study has no statistical
      value. Anyway, function loss was always early on a weight bearing joint. A
      perfect and stable reconstruction gives a higher rate of good result (11 out of
      14). Analysis of cases with anatomic imperfection leads to recommendations:
      fixation of separation fracture, even undisplaced, bone grafting to correct
      impaction, appropriate use of external fixation for neutralization. CONCLUSION:
      Better results should come from a better analysis of the bone lesions :
      separation, impaction or mix fracture. This analysis leads to appropriate
      surgical procedure which give back a stable and anatomic distal tibia. External
      fixation can be usefull for immobilization ; this can't avoid open reduction and
      internal fixation of the fracture. Bone grafting can be useful for impaction
      fracture.

PMID- 8991166
TI  - [Value of intramedullary locked nailing in distal fractures of the tibia].
AB  - PURPOSE OF THE STUDY: This study is a retrospective analysis of 38 extra
      articular distal tibial fractures treated by intramedullary locked nailing.
      PATIENTS AND METHODS: 38 patients with a distal metaphyseal extra-articular
      fracture (43 A AO type) or with minimal ankle joint extension were managed. There
      was 26 men and 12 women with a mean age of 32.3 years, 10 fractures were open.
      The fractures were transverse or oblique in 13 cases, with torsional or flexion
      wedge in 12 cases and spiroid in 13 cases. In only 2 cases was the fibula intact.
      AO classification was not useful because many fractures began more proximally
      than the limit described by Muller. All the fractures were fixed by closed locked
      intramedullary nailing : the nail was cut just after the distal hole and impacted
      close to the subchondral plate. In 7 cases the fibula was fixed too. RESULTS:
      There was no postoperative complication in 27 cases. Three patients had a
      transient nerve palsy (one tibial nerve and two common fibular nerve). In ten
      cases the nail was dynamized. One patient had a non union but healed with a new
      dynamic nail. Two patients had a delayed union and healed after dynamization and
      osteotomy of the fibula. The mean time to union was 5 months (2 to 8). 8 patients
      had a varus or a valgus deformity of 3 to 6 degrees. 11 patients suffered from
      anterior knee pain and in 5 patients the fracture site was painful. In 18
      patients a CT scan was performed : 6 had a rotational deformity from 4 to 26
      degrees, and 2 a tibial lengthening (discrepancy of 7 and 9 mm). CONCLUSION:
      Closed intramedullary nailing is a safe and effective method for the treatment of
      distal metaphyseal tibial fractures. The authors propose a new classification.

PMID- 8991167
TI  - ["Chevron" basal osteotomy of the middle metatarsal bones for static
      metatarsalgia. Apropos of 69 cases].
AB  - PURPOSE OF THE STUDY: Round or flat forefoot metatarsalgia are frequent and
      surgical techniques are various. The authors relate a series with chevron basi
      metatarsal osteotomy. MATERIAL: 69 operated metatarsalgia were reviewed at a mean
      follow up of 5 years. METHODS: The surgical approach was dorsal, aligned on
      metatarsal diaphysis. The basi metatarsal "chevron shape" osteotomy was performed
      using an oscillatory saw, on 1, 2 or 3 metatarsi inducing lowering and
      shortening. This osteotomy wasn't fixed. Weight bearing was allowed at the third
      post-operative day. RESULTS: In 68 per cent of cases, the global result was good
      or very good, but it persisted 32 per cent of post-operative pain either climatic
      or continuous, including 29 per cent metatarsalgia. The plantar corns only
      disappeared one out of twice, but the shoe wearing was improved in 82.6 per cent
      of cases. DISCUSSION: This study showed that the results improved when 3 median
      metatarsal osteotomy were performed simultaneously. The forefoot morphology
      didn't influenced the final result. In fact, this technique includes a good
      result one out of twice in hollow feet. It seems that three metatarsal
      osteotomies induce a metatarsal elevation and shortening, once out of twice.
      CONCLUSION: The advantage of this technique are : a dorsal medio plantar surgical
      approach, an osteotomy realized in cancellous bone and no need for fixation
      allowing a more accurate adjustment of the metatarsal height.

PMID- 8991168
TI  - [Reconstruction of digital pulp by pulp tissue transfer of the toe. Apropos of 15
      cases].
AB  - PURPOSE OF THE STUDY: The authors report their experience of digital pulp
      reconstruction by free toe pulp transfer. Fifteen patients were treated with the
      lateral great toe hemipulp. MATERIAL AND METHODS: 15 cases of post-traumatic
      finger tip reconstruction were reviewed including 9 thumbs, 5 index, 2 medius,
      and one ring finger. There were 6 emergency cases and 9 secondary reconstructions
      (7 after inconvenient spontaneous healing and 2 after groin flap coverage).
      RESULTS: We noted 2 partial necrosis, and 4 patients suffered from cold
      intolerance. The flap sensibility, according to the American Society for Hand
      Surgery criteria, was excellent in 1 case good in 6 cases, fair in 7 cases and
      bad in 1 case. The value of the mean two point discrimination test was 10 mm, the
      mean moving two points discrimination test equalled 9 mm. We had 1 excellent
      functional result, 6 good, 6 fair and 2 bad. The subjective evaluation found 12
      patients satisfied and 3 disappointed. DISCUSSION: A wide range of procedures
      from spontaneous healing to thenar flap, neuro vascular flap or toe pulp transfer
      can be proposed to treat digital pulp loss. In the case of moderate thumb pulp
      avulsion and homodigital volar flap can be proposed; if microsurgery is contra
      indicated, an hetero-digital flap from the index can be performed. When the other
      fingers are concerned, a homodigital flap can be proposed for moderate defects.
      For more important trauma, the thenar flap is convenient to cover the index and
      the medius pulp. Ring and little fingers can be treated by a reverse digital
      artery flap or by a cross finger flap. When a toe pulp transfer is indicated we
      recommend the lateral great toe hemipulp for the thumb and a second or third toe
      pulp transfer for the other fingers when digital vascular anastomosis are
      possible. The great toe hemipulp transfer represented a good indication for
      complete digital pulp loss reconstruction where the thumb is concerned.
      Performing this reconstruction during the acute phase may improve the management
      of those trauma by reducing the time needed for cicatrisation and the length of
      work inability.

PMID- 8991169
TI  - [Spontaneous vertebral pseudarthrosis in ankylosing spondylitis. Apropos of 3
      cases].
AB  - PURPOSE OF THE STUDY: The authors describe the surgical treatment of three cases
      of vertebral pseudarthrosis in two patients suffering from rheumatoid spondylitis
      for an average of 20 years. MATERIAL: Two pseudarthrosis involved the thoracic
      level (T9-T10 and T10-T11), after an insignificant trauma. In the other case, the
      lesion was a secondary localization (L5-S1) arising spontaneously two years after
      the treatment of a T10-T11 lesion. Initial conservative treatment was
      unsuccessful in all three cases. Anterior surgery was performed in all three
      cases. In two out of the three, posterior surgery was associated with the
      anterior approach. RESULTS: After surgery, the three lesions healed. DISCUSSION:
      Extensive discovertebral lesions during the course of rheumatoid spondylitis are
      well known. The authors discuss the pathophysiological mechanisms, the diagnostic
      difficulties of such lesions in patients referred for chronic spinal pain, and
      the choice of treatment. CONCLUSION: Surgical treatment was considered necessary
      in view of the mechanical solicitations of the mobile segment. A double approach,
      both anterior and posterior, gave good results and is advocated by the authors.

PMID- 8991170
TI  - [Disruption of the pubic symphysis with overriding impacted symphysis. Apropos of
      a case].
AB  - INTRODUCTION: The authors report one case of overriding impacted symphysis by
      lateral compression injury of the pelvis. MATERIAL AND METHODS: A 30 year old
      male presented a disruption of the symphysis pubis following a motor vehicle
      accident with lateral injury. Radiographs of the pelvis revealed a displacement
      of the right part of the symphysis behind the left one and a protrusion of the
      left pubic body through the right obturator foramen. CT scan did not show any
      sacro-iliac disruption but a fracture of the lateral part of the sacrum. An
      urethral injury with a complete urethral disruption was associated. Open
      reduction and internal fixation was necessary to reduce displacement. Urethral
      disruption was treated after retrograde urethrogram, four months after injury.
      RESULTS: Two years after injury, there was no pain in the pelvis and urinal
      function was normal. A sexual dysfunction remained. DISCUSSION: This lesion is
      secondary to lateral compression injury with internal rotation of the right part
      of the pelvis. It can be classified in type B2 of Tile's classification. It is a
      rare condition because this mechanism very often leeds to a fracture of the
      pelvic ring.

PMID- 8991171
TI  - [HITS].

PMID- 8991172
TI  - [Morphological and functional neuro-imaging of surgical partial epilepsies in
      adults].
AB  - This article reviews literature on morphological and functional neuro-imaging
      data in refractory partial epilepsies of adults including Magnetic Resonance
      Imaging (MRI); Single Photon Emission Computerised Tomography (SPECT) and
      Positron Emission Tomography (PET). Except for MRI, which is of unquestionable
      utility in the diagnosis of epileptogenic lesions, most of these investigations
      are justified only in the context of pre-operative evaluation of candidates to
      functional neurosurgery. In terms of interpretation the key issue is that of the
      relation between the images and the epileptogenic process itself. The specific
      utility of available techniques is as follows: MRI, in its present state of
      development, reveals a morphological abnormality in more than 80% of the cases
      previously considered as cryptogenic on the basis of X ray Computerised
      Tomography. However, hippocampal atrophy, which has a questionable relation with
      temporal lobe seizures, represents two thirds of abnormal images. Functional MRI
      and MR spectroscopy represent potential alternatives respectively to Wada test
      and interictal SPECT or PET. Ictal blood flow studies during video-EEG monitoring
      represent the major application of SPECT; showing a focal increase of blood flow
      in more than 90% of cases. Interictal SPECT is less informative, but necessary
      for interpreting ictal images. 18F-Deoxyglucose (FDG) PET shows a focal
      interictal hypometabolism in nearly 90% of patients with refractory temporal lobe
      epilepsy. The incidence of interictal hypometabolism is less, though more than
      50%, in the other types of partial epilepsies. For diagnostic purpose PET studies
      of benzodiazepine (BZD)-receptors with 11C-Flumazenil are more widely used than
      those of opiate or mucarinic receptors. The reduced density of BZD receptors is
      likely to reflect neuronal loss, whereas interictal glucose hypometabolism
      reflects both the lesional process and secondary deactivation of perilesional
      areas due to anatomical or functional deafferentation.

PMID- 8991173
TI  - [Dysexecutive syndrome and disorders of motor control in prefrontal mediobasal
      and cingulate lesions].
AB  - Disorders of executive function and motor control are considered to be classical
      consequences of prefrontal lesions. The aim of this study was to investigate
      these disorders and their evolution in a series of patients presenting with
      prefrontal and cingulate lesion following rupture of an anterior communicating
      artery aneurysm. Twenty one subjects were included, and assessed in the secondary
      and late post stroke phases. We have used the following tests to assess planning
      and/or execution time and performance: Trail Making test, Wisconsin Card Sorting
      Test, London Tower Test, Shopping Test of Martin, sequential gestual test and
      contradictory responses test from Luria. Correlations between these parameters
      were used to evaluate subjects strategy. In evaluation of execution time,
      patients were slower than controls, and the difference was more marked using the
      Trail Making Test (p < 0.01) and the London Tower Test (p < 0.01). Furthermore,
      the initiation time was increased in the London Tower Test (p < 0.01), this
      suggesting that they were slower than impulsive. Groups analysis showed that
      their performance level was most often similar to that of of controls, even in
      the secondary phase, with the exception of the number of problems solved whatever
      number of moves in the London Tower test (p < 0.01) and of the percentage of
      errors in the sequential motor task (p < 0.03). Similar results were observed in
      the evaluation of single cases. Correlations between execution time and
      performance were most often significant and negative, in patients and controls.
      These results suggest that the management of the speed-accuracy compromise was
      relatively similar, and that impulsivity, which associates reduction of time to
      poor performance, was absent or mild. Cingulate, and caudate lesions were
      identified as the source of most cognitive disorders.

PMID- 8991174
TI  - [Clinico-radiological data of 48 cases of immunocompetent primary cerebral
      lymphoma].
AB  - In this article clinical and neuroradiological features from a cohort of 48
      immunocompetent patients who have a histologically proved primary cerebral
      lymphoma are considered. Our series consisted of 27 men and 21 women with an
      average age of 59. The clinical results gave 73% patients with a focal deficit,
      46% with deterioration of vigilance, 35% intracranial hypertension, and only 8%
      with epilepsy, which was never revealing. We observed 4 uveitis of which 3
      revealed, and preceded by several months, the neuroradiological manifestations.
      Histological classification using the criterias of the Working Formulation showed
      that 92% of our patients had a large cell lymphoma (class G or H). Precise
      analysis of computed tomography features of 40 patients revealed 46 lesions (most
      of them were isodense) before contrast medium administration. In all the cases,
      the lesion enhancement was intense and homogeneous. In 50% of the cases, there
      were multiple lesions. Sixty lesions were of the supra tentorial compartment,
      lobar in 32 cases, deep in 28 cases. Fifteen were infratentorial. From our
      experience, we can put forward the following suggestions: 1) Neuroradiological
      aspects suggesting primary cerebral lymphomas exist but none of them are
      specific. 2) Research of an uveitis is important, as this makes the histological
      diagnosis more simple. 3)The prescription of corticosteroids should be delayed
      until the histological diagnosis is certain because the primary cerebral
      lymphoma, which is very corticosensitive, is likely to disappear with this
      treatment and then change the biopsy results.

PMID- 8991176
TI  - [Isolated dissection of the posterior cerebral artery].
AB  - Two cases of isolated dissection of the posterior cerebral artery responsible for
      ischemic stroke are reported. Nine probable or certain additional cases were
      found in the literature. Most patients were female. The clinical presentation
      consisted of ischemic symptoms in 6 patients, subarachnoid hemorrhage in 4, and
      both symptoms in 1. Headache was present in almost all patients. The most
      prevalent angiographic picture was an eccentric stenosis followed by fusiform
      dilatation of the P1-P2 segments of the posterior cerebral artery. A double-lumen
      sign was observed in 3 cases. A favorable outcome was usual in cases with
      ischemic symptoms. Potential benefits from anticoagulants (in case of ischemic
      symptoms) or surgery (in case of subarachnoid hemorrhage) are unknown.

PMID- 8991175
TI  - [Sturge-Weber angiomatosis responsible for hemiplegia without cerebral infarction
      in term pregnancy].
AB  - During the third quarter of her pregnancy, a young woman with Sturge-Weber
      angiomatosis had a severe right hemiplegia with hemianopia and aphasia, followed
      48 hours later by focal seizures. Neuroimaging did not show any cerebral lesion
      but contrast magnetic resonance imaging revealed a left hemispheric pial
      angiomatosis. The patient recovered progressively from the third day after a
      ceasarean. The hemianopia disappeared within 15 days, the hemiplegia within one
      month and the aphasia greatly improved within 3 months. Ten weeks after the
      clinical onset, we performed a positron emission tomography study. A decrease
      from 15 to 40% of the cerebral radioactivity was observed after injection of
      water (H2(15)O) or fluorodesoxyglucose (18FDG) in the left temporooccipital area
      adjacent to the meningeal angiomatosis. A chronic and focal olighemia, already
      reported in Sturge-Weber angiomatosis, might participate in the occurrence of
      this cortical metabolic depression.

PMID- 8991177
TI  - [Colliculus hemorrhage].
AB  - We report the case of a patient with mesencephalic hematoma involving only the
      quadrigeminal plate. One case of superior and 3 cases of inferior colliculus
      hematoma have already been reported. Involvement of the quadrigeminal plate
      frequently follows a pontine or an anterior mesencephalic hemorrhage. The cause
      of these hematomas may be due to cryptic malformations of the quadrigeminal plate
      or primitive small size hemorrhages possibly related to the nature of the
      arterial system. Patients with inferior colliculus lesions present a typical
      symptomatology consisting of trochlear nerve palsy contralateral to the lesion or
      bilateral, contralateral hemiparesthesiae and acuphenes. Superior colliculus
      lesion causes upgaze palsy, visual blurring, dizziness and left upper lip
      paresthesiae. The cause of the different signs and symptoms in both types of
      lesion are discussed.

PMID- 8991178
TI  - [Vascular complication disclosing lung cancer in children].
AB  - Stroke are not as rare in pediatric patients as once suspected. Exhaustive
      diagnostic evaluation must be performed, to identify a cause, evaluate risk
      factors of recurrence and propose preventive treatment. We report a case in a
      teen-ager secondary to cerebral embolism. These embols have an exceptional
      origin: pulmonary venous thrombosis, secondary to undifferentiated sarcoma
      located in the lung and extended to pulmonary vein. Stroke by cerebral embolism
      are not always originated from heart disease, and may be misdiagnosed only
      transthoracic echocardiography is realised.

PMID- 8991179
TI  - [Late-onset multiple sclerosis and serum monoclonal gammopathy: an incidental
      association?].
AB  - Four patients older than 45 years with a central nervous system demyelinating
      disease associated to a monoclonal gammopathy are reported. The neurologic
      disease met the diagnostic criteria of multiple sclerosis, with the particularity
      of a late onset. Monoclonal paraproteinemia was also present in the cerebrospinal
      fluid, associated with an intrathecal immunoglobulin synthesis. The clinical data
      and the course of the disease were comparable to the previous reports of late
      onset multiple sclerosis. A causal link between the dysglobulinemia and the
      neurological disease may not be demonstrated. However, such an association may
      underline the role of humoral processes in multiple sclerosis.

PMID- 8991180
TI  - [Hallucinations and thalamic infarction].

PMID- 8991181
TI  - [Marchiafava-Bignami disease: development with flare-up].
AB  - Marchiafava-Bignami disease is a complication of chronic ethanol intoxication.
      The clinical course may be acute, rapidly leading to death, or marked by a
      progressive dementia. A form with favorable outcome is also described. During the
      evolution of chronic forms, acute worsenings are possible, with subsequent
      partial recovery. We report a clinico-radiological case, where a first episode
      was followed by a good outcome. After a second episode, 3 years later, the
      patient developed a dementia with predominant frontal lobe signs. This case
      suggests that, even after a favorable outcome, a long-term poor prognosis cannot
      be ruled out.

PMID- 8991183
TI  - On the influence of physical training on glucose homeostasis.

PMID- 8991182
TI  - [Conference at the Salpetriere. November 1994. Jerky voice, abnormal movements
      and fatal outcome in 2 months in a 66-year-old woman].

PMID- 8991184
TI  - Altered physical state of p210bcr-abl in tyrphostin AG957-treated K562 cells.
AB  - AG957 is a tyrosine kinase antagonist which prior studies had shown inhibits
      p210bcr-abl tyrosine kinase activity and K562 chronic myelogenous leukemia cell
      growth. We report here the effects of AG957 on the physical state of p210bcr-abl
      and its signaling adapter molecules Shc and Grb2 in K562 cells. After exposure to
      AG957, the amount of tyrosine-phosphorylated native p210bcr-abl decreases, with
      the appearance of a high molecular weight (> 210 kDa) p210bcr-abl. This effect is
      seen after [32P]orthophosphate and [35S]methionine labeling. Material suggesting
      the involvement of p210bcr-abl in high molecular weight complexes also appears
      using anti-Shc, anti-Grb2 and anti-phosphotyrosine antibodies. AG957 also acts in
      vitro to shift native p210bcr-abl in anti-p210bcr-abl or anti-Grb2
      immunoprecipitates to higher molecular weight forms under conditions where the
      drug can also act as an antagonist of p210bcr-abl autokinase activity. Incubation
      with dithiothreitol inhibits the appearance of > 210 kDa forms of p210bcr-abl in
      the in vitro reaction. These results leads to the hypothesis that AG957 does not
      act simply as a reversible tyrosine kinase antagonist, but can alter the normal
      amounts and physical associations of molecules important in tyrosine kinase
      signaling. These effects likely reflect covalent cross-links induced by the drug.

PMID- 8991185
TI  - Cremophor EL reversed multidrug resistance in vitro but not in tumor-bearing
      mouse models.
AB  - Cremophor EL (CreEL), a polyethylene castor oil used as a vehicle for cyclosporin
      A and taxol, reverses P-glycoprotein-mediated drug resistance. The vehicle in an
      i.v. dosage form of PSC 833, [3'-keto-Bmt1]-[Val2]-cyclosporin, contains CreEL
      and has been presumed to have the potentiation of the reversal activity of PSC
      833. To examine this possibility, we compared reversal activities of CreEL and
      PSC 833 against multidrug resistance (MDR) in vitro and in vivo. Both CreEL and
      PSC 833 inhibited P-glycoprotein-mediated efflux of [3H]vincristine from
      adriamycin-resistant myelogenous leukemia K562. The sensitization of multidrug
      resistant cell lines to anticancer drugs by CreEL and PSC 833 was selective to
      MDR-related agents, suggesting a specific interference of the P-glycoprotein
      function by the two MDR modulators. The concentration-dependent activity of the
      modulators demonstrated that CreEL is at least 100 times less potent than PSC
      833. The in vivo reversal effects of CreEL alone and PSC 833 in the vehicle were
      investigated in multidrug-resistant tumor-bearing mouse models. In vincristine
      resistant P388 leukemia-bearing mice, neither i.v. nor i.p. administration of
      CreEL even at 1440 mg/kg enhanced the antitumor activity of adriamycin. The in
      vivo negligible activity of CreEL was confirmed in an HCT-15-bearing athymic
      mouse model. In contrast, PSC 833 significantly enhanced the antitumor activity
      of adriamycin in the in vivo models. The reversal activity of CreEL restricted to
      in vitro leads us to conclude that the vehicle containing CreEL did not
      potentiate the activity of PSC 833 in the tumor-bearing mouse models.

PMID- 8991186
TI  - In vitro detection of the MDR phenotype in rat myocardium: use of PCR,
      [3H]daunomycin and MDR reversing agents.
AB  - A decrease in the intracellular drug concentration in resistant cells as compared
      to sensitive cells is one of the characteristics of the MDR phenotype. P
      glycoprotein (Pgp) is thought to be responsible for an active efflux of some
      lipophilic drugs such as anthracyclines. Anthracyclines such as daunomycin are
      highly effective anticancer agents but induce a well-described, while
      incompletely explained, cardiac toxicity. In this study, we investigated the MDR
      phenotype in rat myocardium in terms of gene expression, detection of Pgp and
      indirect evaluation of Pgp function. A clear mdr1a gene specific expression in
      rat cultured myocardial cells and cardiac tissue was detected by RT-PCR. The
      incorporation of [3H]daunomycin in myocardial cell cultures was studied with and
      without reversing agents. Daunomycin was found to have a high accumulation in
      cardiac cells illustrated by a Ci/Ce ratio of 2890. This high accumulation was
      moderately but significantly (p < 0.05) increased in the presence of a MDR
      reversing agent such as verapamil, PSC 833 or S9788. These results suggest that
      blockade of the Pgp in humans may result in an increased toxicity of several Pgp
      substrates in normal tissues like the myocardium.

PMID- 8991187
TI  - Increase of P-glycoprotein-mediated drug resistance by hsp 90 beta.
AB  - The expression of heat shock proteins hsp27, hsp60, hsp70, hsp90 alpha and hsp90
      beta in extracts of three cell lines (LoVo DxR, KBChR8-5 and S180 DxR) expressing
      the MDR (multidrug resistance) positive phenotype as well as in the sensitive
      parental lines has been investigated. We present evidence that heat shock protein
      hsp90 beta is associated with the P-glycoprotein (Pgp or P170) one of the most
      prominent components of the drug resistance machinery. In the doxorubicin
      resistant cell line LoVo DxR, but not in the sensitive parental line, hsp90 beta
      is expressed constitutively as shown by Northern blotting. The expression of
      hsp90 beta in the sensitive LoVo cell line, however, can be induced by exposure
      of the doxorubicin-sensitive parental cell line to different stress factors
      (dexamethasone, doxorubicin, heat treatment or cadmium chloride). We were able to
      demonstrate that hsp90 beta can be co-precipitated along with Pgp and vice versa.
      In native agarose gels both proteins migrated together as one single band as
      shown by Western blot analysis. This intracellular protein-protein interaction
      may present a mechanism for the modulation of Pgp function possibly by a
      stabilization of the protein which seems to be attributed to hsp90 beta (in the
      human colon carcinoma cell line and in the murine cell line S180). Antisense
      experiments with oligonucleotides directed against hsp90 beta and Pgp,
      respectively, showed a synergistic effect of the selected hsp90 beta antisense
      oligonucleotide in combination with the previously described Pgp antisense
      oligonucleotide in reducing the doxorubicin resistance. The hsp90 beta antisense
      oligonucleotide when applied in addition to the Pgp antisense oligonucleotide
      increased the doxorubicin sensitivity of the resistant human colon carcinoma cell
      line 2-fold. On the contrary, the hsp90 beta antisense oligonucleotide alone in
      contrast to the Pgp antisense oligonucleotide alone did not cause a reduction of
      the chemoresistance. Moreover, Pgp half-life was reduced in the presence of both
      antisense oligonucleotides as compared with an incubation with an anti-Pgp
      antisense oligonucleotide alone.

PMID- 8991188
TI  - Liver function tests and lidocaine metabolism (MEGX test) during i.v. CMF therapy
      in breast cancer.
AB  - The measurement of monoethylglycinexylidide (MEGX test) is considered a sensitive
      method for the evaluation of hepatic metabolic capacity. The multidrug
      chemotherapy CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/ m2, 5
      fluorouracil 600 mg/m2) is widely used in breast cancer patients but very few
      clinical studies have investigated its possible liver toxicity. We have
      prospectively evaluated the possible acute liver toxicity after a cycle (i.e. two
      courses) of CMF by means of the measurement of standard liver function tests and
      of MEGX, i.e. the main lidocaine (Lid) metabolite after the i.v. injection of
      Lid. Consecutive patients (n = 15), aged 43-68 years, were radically operated on
      because of M0 primary breast cancer and candidates for adjuvant CMF because of
      nodal axillary involvement (pN1) were studied. Tests were performed before the
      first (given at day 1) and 48 h after the second course (given at day 8) of an
      i.v. CMF regimen to be repeated every 28 days. Full blood count, serum ALT, AST,
      gamma-GT, alkaline phosphatase and albumin were measured with standard methods.
      To investigate the appearance of MEGX, blood samples were taken before, and 5,
      10, 15, 20, 25, 30 and 60 min after i.v. Lid injection. MEGX serum concentration
      was measured by means of a fluorescent polarization immunoassay. We found no
      significant variation between pre- and post-CMF standard liver function tests
      with the exception of ALT levels, which, however, decreased (mean 48%, p < 0.05).
      The MEGX serum concentration was significantly increased over the sampling time
      period and the 42% mean rise was statistically significant (p < 0.001). Moreover,
      the post-CMF increase of circulating MEGX was steeper than the basal pre-CMF
      values. The slopes relating to the curves of MEGX formation over the first 20 min
      were 3.30 and 2.24, respectively (p < 0.001). In conclusion, no hepatic acute
      toxicity was observed during the CMF chemotherapy. Further studies are required
      to understand the meaning of the unexpected MEGX rise.

PMID- 8991189
TI  - Camptothecin exhibits selective cytotoxicity towards human breast carcinoma as
      compared to normal bovine endothelial cells in vitro.
AB  - We have reported earlier that camptothecin (CPT) incorporated into multilamelar
      liposomes of appropriate lipid composition displayed effective anti-tumor
      activity with minimal host toxicity in a nude mouse model xenographed with the
      human breast carcinoma Clouser nut 1. To investigate this observation further, we
      have determined the differential effects of CPT on the Clouser tumor cells as
      well as normal vascular (BVEC) endothelial cells in culture. We report here that
      Clouser cells are approximately 200-fold more sensitive to CPT (IC50 = 4.0 nM)
      than the normal endothelial cells (IC50 approximately 1 microM) as assayed by
      MTT; however, CPT demonstrates a potent anti-proliferative activity on both cell
      lines at low drug concentrations as measured by [3H]thymidine uptake. At higher
      concentrations (> 25.0 nM), however, the Clouser cells maintained a higher
      percentage of cells capable of incorporating [3H]thymidine. No significant
      differences in the levels of topoisomerase 1 protein and in vitro enzymatic
      activity were seen; although, the Clouser cells showed a 2-fold greater incidence
      of cleavable complex formation by CPT in vivo. Based on the data presented here,
      we propose that the selective cytotoxic activity of CPT towards tumor cells may
      be a function of the tumor cells' reduced ability to prevent cleavable complex
      formation. We also propose that the antitumor effect of CPT may be enhanced in
      vivo by its anti-proliferative effect on vascular endothelial cells which are
      normally solicited to promote tumor growth.

PMID- 8991191
TI  - Polyamine levels in various tissues of rats treated with 3-hydroxy-4
      methoxycinnamic acid and 3,4-dimethoxycinnamic acid.
AB  - The effects of 3-hydroxy-4-methoxycinnamic acid (3H4MCA) and 3,4
      dimethoxycinnamic acid (3,4DMCA) on body weight, organ weight, and the contents
      of putrescine, spermidine and spermine in 15 different tissues were examined in
      rats that had been given these compounds for 5 days. In 3H4MCA-treated rats, the
      weight of the spleen was significantly increased, while none of the other organs
      showed any significant changes. A diet containing either 3H4MCA or 3,4DMCA should
      not be taken by patients bearing cancers in the seminal vesicles, spleen or
      liver, and a diet containing 3,4DMCA should not be taken by patients bearing
      cancers in the testis, kidney, muscle, small intestine or brain (cortex) because
      of the significant increases in polyamines, which are associated with a risk of
      cancer growth, in these tissues. However, a diet containing 3H4MCA is recommended
      for the management of cancers in the skeletal muscle (femoral), tongue, small
      intestine (jejunum), stomach, lung and brain based on reductions in polyamines
      which stimulate tumor growth. A diet containing 3,4DMCA is also recommended for
      cancer in the prostate, thymus and stomach for the same reason. In addition, a
      synergic therapeutic effect for the treatment of cancers in these tissues may be
      anticipated by a combination of such a diet with anti-cancer drugs which reduce
      polyamine levels. The metastasis of cancers in these tissues may also be
      inhibited by the reduction of polyamines by these acids. The ratio of spermidine
      to spermine was significantly higher in the lung of 3H4MCA-treated rats, and
      lower in the seminal vesicle, thymus, kidney, heart, tongue, stomach and lung of
      3,4DMCA-treated rats, than in control rats. The present experiment indicated that
      cancer patients should pay careful attention to endogenous polyamines in tissues
      bearing tumors induced by chemicals in ingesta and anti-cancer drugs, in addition
      to exogenous polyamines.

PMID- 8991190
TI  - Evaluation of [131I]iodoerythronitroimidazole as a predictor for the
      radiosensitizing effect.
AB  - The aim of this study was to evaluate whether radiolabeled
      iodoerythronitroimidazole (IETNIM) could predict the radiosensitization effect on
      tumors. Tumor-bearing mice were irradiated at a dose of 25, 31 and 37 Gy after
      the injection of IETNIM. They were also exposed to 37 Gy radiation at 35, 70, 140
      and 240 min after the i.p. injection of IETNIM. After the irradiation, tumor
      growth assays were conducted and the effect of IETNIM as a radiosensitizer was
      estimated as enhancement factor (EF). Tumor uptake was measured at 35, 70, 140
      and 240 min after i.p. injection of [131I]IETNIM, which were the same intervals
      used in the radiosensitization study. EF of IETNIM in mice treated with 25, 30
      and 37 Gy irradiation was 0.72, 0.98 and 1.28, respectively. EF of IETNIM in mice
      irradiated at 35, 70, 140 and 240 min after the injection was 1.50, 1.69, 1.46
      and 1.08, which corresponded to the tumor uptake and blood clearance of
      [131I]IETNIM. [131I]IETNIM may be a suitable radiopharmaceutical to predict the
      radiosensitization effect of misonidazole analogs on tumors.

PMID- 8991192
TI  - 5-substituted-2-thiohydantoin analogs as a novel class of antitumor agents.
AB  - Certain series of 2-thiohydantoin derivatives, carrying various substituents at
      position 5 such as 5-bromo-2-thienylmethylene, 5-(2-carboxyphenylthio)-2
      thienylmethylene and 2-methylene-4H-thieno[2,3-b][1]benzothiopyran-4-one, were
      evaluated for their antitumor activity. Compound 5-(5-bromo-2-thienylmethylene)-3
      morpholinomethyl-2-(2,3,4,6 -tetra-O-acetyl -beta-D-glucopyranosylthio)hydantoin
      proved to possess a broad spectrum antitumor activity against a wide range of
      different human cell lines of nine tumor subpanels causing both cytostatic and
      cytotoxic effects, resulting in full panel median growth inhibition (GI50) and
      total growth inhibition (TGI), with a median lethal concentration (LC50) at 15.1,
      41.7 and 83.2 microM, respectively. On the other hand, compound 5-(5-bromo-2
      thienylmethylene)-2-thiohydantoin and compound 5-(5-bromo-2-thienylmethylene)-3
      phenyl-2- (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-thio)hydantoin showed
      potential selectivity against leukemia cell lines. Further derivatization of
      these compounds, deduced from the obtained tentative structure-activity
      relationships, may lead to more potent agents.

PMID- 8991193
TI  - A pharmacological pilot study: application of an intermittent schedule of oral
      uracil and ftorafur (UFT) for hepatocellular carcinoma patients.
AB  - Patients with hepatocellular carcinoma (HCC) are highly compromised by failing
      liver function. To retain good compliance in the administration of uracil and
      ftorafur (UFT) in such patients, an intermittent schedule for oral administration
      of UFT was expected to have the same effect as daily continuous use without
      affecting liver function. A pharmacological pilot study was carried out to
      confirm the efficacy of this schedule. Sixteen patients with HCC who underwent
      hepatectomy were given UFT 200 mg b.i.d. for five consecutive days. Blood samples
      were drawn before the last administration of UFT and at the operation (2 days
      after the last administration of UFT), and the tumor and adjacent liver tissue
      were collected. The concentration of ftorafur (FT), 5-fluorouracil (FUra) and
      uracil (Ura) in serum and liver tissue were measured. Oral administration of UFT
      200 mg b.i.d. resulted in a trough level of FT, FUra and Ura in serum of 9.4
      micrograms/ml, 13.3 ng/ml and 64.2 ng/ml, respectively. At the operation, FT and
      FUra in serum had decreased significantly. However, FUra in tissue was still
      higher than that in serum, in contrast to the results for FT and Ura. There was
      no difference in the concentration of FUra between the tumors and adjacent liver
      tissues. No side effect was noted in any of the patients. These results indicated
      that an intermittent schedule for the administration of oral UFT is not only
      tolerable but also effective because a sufficient concentration of FUra in the
      liver tissue is reached and maintained.

PMID- 8991194
TI  - Remission of advanced uterine leiomyosarcoma with pulmonary metastases with
      carboplatin and paclitaxel.
AB  - A patient who had a high-grade uterine leiomyosarcoma (LMS) with extensive intra
      abdominal and pulmonary metastases at the time of diagnosis underwent
      supracervical hysterectomy, bilateral salpingo-oophorectomy and tumor reductive
      surgery. She then received induction chemotherapy with paclitaxel 135 mg/m2 over
      24 h and carboplatin (target AUC = 7.5 mg.ml/min) monthly for seven courses,
      achieving remission with a small amount of residual disease. The treatment was
      well tolerated except for peripheral neuropathy. Accordingly, the combination of
      carboplatin and paclitaxel may be considered in patients with advanced high-grade
      LMS of the uterus, and this regimen warrants further study in this disease.

PMID- 8991195
TI  - A phase II trial of docetaxel in advanced non-small cell lung cancer.
AB  - Twenty-nine patients with locally advanced or metastatic non-small cell lung
      cancer (NSCLC) were treated with docetaxel. Ten patients had already received
      chemotherapy, the others had received no chemotherapy. Docetaxel was
      administrated i.v. over 60 min every 21 days at a dose of 100 mg/m2. Twenty-three
      patients were evaluable for response. There were no complete responses and eight
      partial responses. The overall response rate was 35% (28% in the intent to treat
      analysis). Median duration of response was 43 weeks and median time to
      progression 12 weeks. Neutropenic infections, neurotoxicity and asthenia were
      dose-limiting toxicities (6% of 118 cycles). The other main toxicities were
      asthenia in 48%, skin reactions in 31% and nail changes in 31% of the patients.
      Single-agent docetaxel appears to be active against both previously treated and
      untreated advanced NSCLC. Toxicity was acceptable but should be carefully
      monitored.

PMID- 8991197
TI  - [Laparoscopic treatment of non parasitic liver cysts].
AB  - Various surgical treatments have been proposed for highly symptomatic hepatic
      cysts: enucleation, fenestration, hepatic resection and liver transplantation.
      The advent of laparoscopic surgery has provided new opportunities but, at the
      same time, has increased the uncertainties concerning the correct management of
      these patients. This study evaluates the results and defines the indications for
      laparoscopic fenestration of symptomatic nonparasitic hepatic cysts, either
      solitary or diffuse. 31 patients were observed between November 1990 and October
      1995: 15 with solitary cysts and 16 with policystic liver disease (PLD). After a
      careful review of the symptoms, 8 patients (5 with a solitary cyst and 3 with a
      PLD) were excluded from surgical treatment and 23 were treated by laparoscopic
      fenestration. There was no mortality. Ten of the 23 patients had a solitary cyst
      with a median diameter of 11.6 cm (range 6-20 cm). No conversion to laparotomy
      was necessary. There were no complications and complete regression of symptoms
      was obtained in all patients. No recurrences were observed. In the PLD group (13
      patients), two patients had to be converted to open fenestration (15%). There
      were no deaths and the surgical morbidity was limited to two cases of
      postoperative persistent ascites. Symptomatic relief was obtained in 64% of
      patients, but symptoms recurred in 36%. A subgroup of PLD at high risk for
      recurrence was identified and a classification of PLD is proposed: PLD type I
      characterized by large cysts mainly located in the anterior hepatic segments, and
      PLD type II characterized by numerous small cysts through the liver which do not
      represent a good indication for laparoscopic fenestration.

PMID- 8991196
TI  - Phenobarbital administration does not affect high-dose ifosfamide
      pharmacokinetics in humans.
AB  - Ten patients (three males and seven females) were treated for sarcoma with high
      dose ifosfamide (IFO) according to a 4 g/m2 1 h i.v. infusion schedule every day
      for 3 days. The courses were repeated every 4 weeks. Phenobarbital (PB) treatment
      was only started at the second course and was continued for the following courses
      at a p.o. dose of 60 mg/ day on the 3 days of IFO i.v. infusion. IFO
      pharmacokinetic studies were performed on the first and third day of each course.
      The results of the pharmacokinetic analysis showed a statistical difference of
      the IFO parameters between the first and third day of each course with or without
      PB co-administration. When we compared all the first days and all the third days,
      the statistical analysis showed no difference for all the pharmacokinetic
      parameters. The meaning of these results was that IFO kinetics was not stationary
      with an area under the curve decreasing from the first to the third day of each
      course and that concomitant PB administration, in our administration schedule,
      did not influence IFO pharmacokinetics.

PMID- 8991198
TI  - [Complications of two types of pancreatic anastomosis after
      pancreaticoduodenectomy].
AB  - The operative mortality rate after pancreaticoduodenectomy (PD) is 5% or less at
      major surgical centers and is generally related to pancreatic anastomosis
      complications. Recently, several authors have reported a low incidence of
      complications after PD using pancreaticogastrostomy. The aim of our work was to
      retrospectively study the operative complications of pancreaticogastrostomy (PG)
      and pancreaticojejeunostomy (PJ) after PD. Since 1989 we have performed 59
      consecutive DP, in 33 male patients and 22 female patients, with a mean age of 56
      +/- 12 years. We performed 43 PG and 16 PJ. In 42/59 cases, PD was performed for
      malignant disease. Pancreaticoduodenal resection was identical in both groups,
      with classical pancreatic transection performed at the level of the
      mesentericoportal axis. The overall mortality rate in this study was 5.08% (n =
      3). It was 4.65% (n = 2) in the PG group and 6.25% (n = 1) in the PJ group.
      Operative complications were absent in 36 patients (24 PG, 12 PJ). The mean
      postoperative hospital stay was 17 +/- 6 days; 23 patients (19 PG, 4 PJ)
      presented one or several complications. 12 patients required re-exploration (10
      PG, 2 PJ). Pancreatic fistula occurred in 8 patients (13.55%), 14% (n = 6) in the
      PG group and 12.5% (n = 2) in the PJ group. In each group, only one pancreatic
      fistula was re-explored. Seven patients (16%) in the PG group presented
      postoperative pancreatitis. Pancreatic fistula and postoperative pancreatitis
      occurred in a pancreas with a normal texture and non-dilated pancreatic duct in
      every case, with one exception (PJ). During long term follow-up, 18 patients died
      from cancer (12 PG, 6 PJ). In conclusion, this study suggests that PG does not
      decrease the pancreatic fistula or postoperative pancreatitis rates and that
      these complications are essentially related to pancreatic texture and pancreatic
      duct.

PMID- 8991199
TI  - [Intraoperative radiotherapy in cancers of the pancreas and in recurrent
      colorectal cancers].
AB  - The aim of this study was to evaluate intraoperative radiotherapy in exocrine
      pancreatic cancer (n = 10) and in recurrent colorectal carcinoma (n = 11).
      Radiotherapy was delivered with electron beams (energy from 9 MeV to 20 MeV).
      Doses ranged from 15 Gy to 25 Gy. All patients with pancreatic cancer also
      received 40 Gy external beam irradiation and 5-Fluorouracil (500 mg/m2) and eight
      patients with recurrent colorectal carcinoma received postoperative external beam
      irradiation (20 Gy to 60 Gy). There were no postoperative deaths or complication.
      In pancreatic cancers, pain relief (7 cases) until death was observed in all
      cases. After palliative procedures (9 cases), the median survival time was 6
      months (ranging from 4 months to 14 months). One patient is alive with a follow
      up of 5 years and 6 months following total pancreatectomy. 5 patients with
      recurrent colorectal carcinoma, died with a median survival time of 13 months
      (ranging from 2 months to 25 months), and six patients are alive. Two of them
      have recurrence, and four are free of recurrence with a mean follow-up of 21
      months (ranging from 3 months to 54 months). In conclusion, our results for
      pancreatic cancer agree with the disappointing results reported by other
      institutions. On the other hand, recurrence of colorectal carcinoma seems to be a
      good indication for intra-operative radiotherapy even when resection is
      incomplete.

PMID- 8991200
TI  - [Abdominal parietoscopy. Technique and indications. Preliminary results: 7
      cases].
AB  - A new videosurgical approach is described. CO2 directly inflated into the
      abdominal wound, in front of the musculo-aponevrotic area, creates a large space
      allowing repair of small abdominal wound defects with excellent plastic results.
      7 preliminary cases are reported with a 3-month follow-up.

PMID- 8991201
TI  - [Management of caustic esophagitis in adults].
AB  - The experience of surgical management of caustic ingestion in adults started a
      quarter of a century ago in the Paris Poisons Centre. It was found that, inasmuch
      as certain cases of massive ingestion require major emergency surgery, the
      patient must be received by a competent surgical unit, associated with an
      Intensive Care Unit with permanent availability of gastrointestinal and
      tracheobronchial fibroscopy. The assistance of an ENT surgeon can be precious,
      and a psychiatrist is often necessary. The Saint Louis Hospital visceral surgery
      unit in Paris has developed a specialized on-call system. Its current experience
      concerns approximately one thousand patients. Comparison with other French or
      European experiences at the time of preparation of this report, presented to the
      97th French Surgery Congress in 1990, allows the definition of a consensual
      management.

PMID- 8991202
TI  - [Stereotaxic mammary microbiopsy. I. Technical aspects].
AB  - The authors present a review of the literature about the procedure of
      stereotactic core breast biopsy. Developed since the beginning of the 1990s, this
      histopathological sampling technique presents numerous advantages. Its low cost,
      its simplicity and its diagnostic efficacy are the main arguments for its
      development. The diagnostic efficacy confirmed on clinical trials (see 2nd part
      of article) must be preserved if core biopsy is performed routinely. This means
      avoiding wrong choices in indications and respecting evaluated procedures.

PMID- 8991203
TI  - [Stereotaxic mammary core biopsy. II. Complementarity or competition with
      surgical biopsy].
AB  - In breast disease, the only resemblance between needle core biopsy and fine
      needle aspiration cytology is the mammographic guide to puncture. On selected
      cases, the efficacy of needle core and surgical biopsy is similar. Inclusion of
      core breast biopsy in the diagnostic tools requires a repeated pluridisciplinary
      concentration.

PMID- 8991204
TI  - [Carney's syndrome: 2 new cases].
AB  - The association of gastric leiomyoblastomas, pulmonary chondromas and extra
      adrenal paragangliomas has been called "Carney's Triad" since 1977. It is
      incomplete when only two of these lesions are present. 42 cases has been
      published. We report observations of two young women with gastric
      leiomyoblastomas and pulmonary chondromas; one of them also had an adrenocortical
      adenoma.

PMID- 8991205
TI  - [Primary colonic type appendicular adenocarcinoma in a 17 years old patient. Plea
      for routine pathologic examination in the young].

PMID- 8991206
TI  - [Closed colonic perforation secondary to foreign body. Endoscopic diagnosis].

PMID- 8991207
TI  - The "kite flap" for dorsal thumb reconstruction.
AB  - Skin cover for losses of substance on the dorsum of the thumb is often difficult.
      The "kite flap", introduced by Foucher, is ideal for this purpose. In the period
      between 1988 and 1993, this flap was used in five patients presenting with skin
      defects on the dorsum of the thumb. The results obtained have convinced us to
      consider this technique as the first method of choice in this area of
      reconstructive surgery.

PMID- 8991208
TI  - Replantation by arterialization of the venous system of amputated parts.
AB  - Only in four cases out of 800 replantations and revascularizations as the last
      resort it was necessary to anastomose an artery of the stump to a vein of the
      amputated part. Three of these cases were very distal finger amputations in zone
      II and III and one was an auricle amputation with so severely damaged arteries of
      the amputated part that it was not possible to perform their anastomosis. All of
      these four clinical cases were successful and they confirm the possibility of
      arterialization of the venous system which was proved in experiments with rabbit
      auricle replantation by Mundy and Pajn (1994) and by Farrior and Baker (1988).

PMID- 8991209
TI  - The management of extensive tumours of the scalp.
AB  - Though tumours of the scalp and skull are not very common certain severe and
      extensive forms are associated frequently with intracranial propagation and
      therefore their reconstruction represents often a major problem requiring the use
      of a series of surgical methods. Their treatment requires the use of expanders,
      local flaps, pedicled cutaneous and musculocutaneous flaps, as well as free
      flaps. This report deals with 10 patients with localized extensive tumours larger
      than 120 cm2 within the region of the scalp and skull subjected to various
      reconstruction procedures. The applied surgical techniques are discussed and
      attention is devoted also to the involvement of bone in the above mentioned
      localization as well as to the problems associated with these lesions.

PMID- 8991210
TI  - The relation of isolated cleft of the hard palate to submucous cleft palate.
AB  - The authors report a case of a spontaneous development of a fistula in a
      nonoperated submucous cleft palate in a male aged 40 years. This observation and
      the search of the underlying causes are based on their report from 1971 dealing
      with an analysis of 5 cases of an inborn defect in the hard palate.

PMID- 8991211
TI  - Nose deformation as a result of birth injury.
AB  - The authors have compared the frequency of occurrence of nasal septum deformation
      in two groups of newborns, using the simplest testing methods for: 1. newborns
      born by spontaneous labor (254 newborns), 2. newborns born by caesarean section
      (52 newborns). The deformation from the central position of the nose were found
      in 2 newborns from group 2 (3.9%) and in as many as 50 newborns from group 1
      (approx. 20%) providing the evidence that most deformations occur as a result of
      birth injury (during labor). 32 deformations (26 in the cartilaginous section of
      the nasal septum and 6 in the osseous section) have been tested repeatedly in the
      third or fourth week of life. 19 out of 26 deformations of the cartilaginous
      section of the nasal septum (73%) have been repositioned automatically. All
      deformations in the osseous section detected after birth were also analyzed
      physically in the third or fourth week of life.

PMID- 8991212
TI  - The primary treatment of severe burn hand by flap plastic.
AB  - The author has summed up the experience from the treatment of severely burn hand.
      A deep burn of the hand is always a severe injury since it may be the cause of
      partial or full disability. Over the last 12 years (between April 1983 and March
      1995) the Prague Burn Centre hospitalized altogether 182 cases of severe burn
      hands aged between 3 and 74 years. In all injuries an early necrectomy was
      carried out and the surface was covered with temporary cover. The depths of the
      injury is properly treated, becomes usually obvious after 4 days after the injury
      and then it is possible to cover the necrectomised areas with various types of
      flap plastics. The aim is the greatest possible return of the useful function and
      a satisfactory cosmetic result.

PMID- 8991214
TI  - Evaluating the international humanitarian system: rationale, process and
      management of the joint evaluation of the international response to the Rwanda
      genocide.
AB  - The Rwanda evaluation has been termed a landmark in evaluation, not only because
      of its quality and the insights it has produced. It was also an unprecedented
      international collaboration to learn the lessons from the immense tragedy that
      was the genocide in Rwanda and its aftermath. This paper reports on the
      rationale, process and management of the joint evaluation of the international
      response to the Great Lakes crisis of 1994-5.

PMID- 8991213
TI  - Emergency care of severe burn children (an experience of Prague Burn Centre).
AB  - The control of a shock associated with burns has marked effects on the further
      course of burn injuries. In spite of the steadily increasing improvement of
      intensive care of severe burn children sometimes are not applied essential
      recommended procedures which are necessary during the first aid and the transport
      of burn cases to a burn centre. These procedures are determined by the assessment
      of a lot factors. A misinterpretation of these factors can lead to an
      insufficient or to an excessively aggressive therapy with their sequelae. This
      holds true both for a local and for a systemic therapy of severe burn children.
      The most important problems are documented by 2 case reports.

PMID- 8991215
TI  - Early warning and response: why the international community failed to prevent the
      genocide.
AB  - The enormity of the genocide in Rwanda demands that it be subjected to searching
      enquiry and that members of the international community, collectively and
      individually, examine their own roles in the event. This paper draws extensively
      on Study II of the Joint Evaluation, and examines the effectiveness of
      international monitoring (early warning) and management of the Rwanda conflict.
      It is not intended to explore all the factors which together contributed to the
      genocide that were or might have been amenable to modification by the
      international community. The focus is on warning and response beginning with the
      start of the civil war in 1990, and culminating in an analysis of the
      international response to the genocide in April-June 1994.

PMID- 8991217
TI  - Why aid agencies need better understanding of the communities they assist: the
      experience of food aid in Rwandan refugee camps.
AB  - Refugee views on food aid reveal the ignorance of the international community
      regarding Rwandan culture, economy and politics. This ignorance carries a number
      of costs. On one level, the main cost is that a professional service is not
      carried out to the best of one's ability. Ignorance of Rwanda's North-South
      divide, for instance, has caused agencies to be insensitive to in-camp
      discrimination based upon regional identity and its impact on programme
      activities. On a deeper level, agency ignorance about Rwandan culture, economy
      and the dynamics of camp politics, reduces refugee confidence in humanitarian
      agencies and workers. Better information would not only result in the greater
      likelihood of appropriate responses to specific needs, but would also encourage
      greater credibility in the political arena where the ultimate stake is to see
      lasting peace and a dignified return of refugees to their homes.

PMID- 8991216
TI  - An account of co-ordination mechanisms for humanitarian assistance during the
      international response to the 1994 crisis in Rwanda.
AB  - This paper examines the co-ordination strategies developed to respond to the
      Great Lakes crisis following the events of April 1994. It analyses the different
      functions and mechanisms which sought to achieve a co-ordinated response--ranging
      from facilitation at one extreme to management and direction at the other. The
      different regimes developed to facilitate co-ordination within Rwanda and
      neighbouring countries, focusing on both inter-agency and inter-country co
      ordination issues, are then analysed. Finally, the paper highlights the absence
      of mechanisms to achieve coherence between the humanitarian, political and
      security domains. It concludes that effective co-ordination is critical not only
      to achieve programme efficiency, but to ensure that the appropriate instruments
      and strategies to respond to complex political emergencies are in place. It
      proposes a radical re-shaping of international humanitarian, political and
      security institutions, particularly the United Nations, to improve the
      effectiveness of humanitarian and political responses to crises such as that in
      the Great Lakes.

PMID- 8991218
TI  - Food aid and nutritional programmes during the Rwandan emergency.
AB  - In contrast to several other recent emergencies, the response of the
      international relief community to the Rwandan emergency appears largely to have
      prevented widespread malnutrition and related mortality. While it is true that
      aspects of the response in the food and nutrition sector were in various ways
      open to criticism and may have contributed to unnecessarily high levels of
      wasting in some camps at various points in time, the appalling excesses of famine
      witnessed in other recent African crises was not revisited during this emergency.
      Indeed, the main factors contributing to mortality and morbidity during the
      Rwandan emergency were violence and epidemics rather than lack of food and
      nutritional support.

PMID- 8991219
TI  - First International Conference on Emergency Settlement, University of Wisconsin,
      Madison, Wisconsin, 15-20 April 1996.

PMID- 8991220
TI  - An absurd restriction to the practice of otolaryngology.

PMID- 8991221
TI  - Friedrich von Bezold (1842-1908).

PMID- 8991222
TI  - Disposable epicutaneous skin tests.

PMID- 8991223
TI  - Classification of chronic suppurative otitis media: type VI.

PMID- 8991224
TI  - Passavant's ridge: is it a functional structure?

PMID- 8991225
TI  - Chronic voice abuse and bilateral vocal fold cysts.

PMID- 8991226
TI  - Argon laser and Gherini-Causse Endo-Otoprobe in otologic surgery.
AB  - The authors describe the various surgical indications and techniques of the argon
      laser and Gherini-Causse Endo-Otoprobe in otologic surgery, from otosclerosis to
      chronic otitis. The advantages are numerous, permitting the surgeon to vaporize
      or coagulate tissue with optimal effect, avoiding excessive mobilization of the
      ossicular chain and diminishing the risk of damage to the facial nerve and inner
      ear structures.

PMID- 8991227
TI  - Ancient schwannoma of the submandibular gland: a case report.
AB  - Schwannomas (neurilemmomas) are neurogenic tumors that arise from the Schwann
      cells of the neural sheath. They are most often benign and solitary. Extracranial
      schwannomas are rare, and can be mistaken for metastatic disease or other non
      neurogenic tumors. Ancient schwannoma is a rare variant of schwannoma with a
      course typical of a slow-growing benign tumor. Histologically, it can be confused
      with a malignant mesenchymal tumor. An unusual case of an ancient schwannoma of
      the submandibular gland is reported. The clinical, histological and surgical
      aspects of this tumor are discussed, and the literature regarding this rare
      entity is reviewed.

PMID- 8991228
TI  - Vocal fold hemorrhage.

PMID- 8991229
TI  - Parapharyngeal lymphangioma mimicking a peritonsillar abscess.

PMID- 8991230
TI  - The 3849 + 10 kB C-->T mutation in a 21-year-old patient with cystic fibrosis.
AB  - Cystic fibrosis (CF) is the most common lethal inherited disease in the white
      population. It is characterized by exocrine gland epithelia dysfunction, which
      leads to pulmonary and pancreatic insufficiency. Since the cloning of the CF gene
      in 1989 and the identification of the most common CF mutation (delta F508), more
      than 400 different mutations have been described. These mutations appear to
      contribute to the heterogeneity of the CF phenotype and several reports have
      speculated on the relationship between the most common CF mutations and the
      patient's clinical status. We report the case of a 21-year-old woman with
      longstanding chronic pansinusitis, nasal polyposis, chronic cough and severe
      nasal crusting. During a period of five years she had been followed by her
      otolaryngologist and pediatric pulmonologist. Sweat tests performed at the age of
      17 and 18 were within normal limits and she underwent repeated conventional
      sinonasal procedures, with no improvement in her clinical status. On her present
      admission, sweat tests showed a 70 meq/l chloride concentration. The diagnosis of
      CF was then confirmed by DNA analysis and the patient was found to carry the 3849
      + 10 kB C-->T mutation. The early detection of this newly recognized form of CF
      in adults as well as in children presenting with sinonasal symptoms is critical
      for life expectancy and quality.

PMID- 8991231
TI  - Atypical intranasal foreign body.
AB  - This report records the findings of a long-standing intransasal foreign body in a
      six-year-old boy from a remote, semidesert region of Kenya. He had nasal
      obstruction for 20 months and as a result had developed chronic otitis media and
      severe malnutrition. Removal of the mass was accomplished piecemeal by
      aspiration, revealing that the entire septum and both lateral nasal walls had
      been destroyed by the process, thought to be due to a vegetal foreign body.
      Following removal of the foreign body, his health improved, the otitis media
      cleared up and he gained weight.

PMID- 8991232
TI  - The origin of the sickle cell gene.

PMID- 8991233
TI  - Haemoglobin C gene in south eastern Nigeria.
AB  - Haemoglobin C (Hb C) is very rare in eastern Nigeria (east of River Niger).
      Isolated cases have been reported. The incidence is however as high as 6% in
      western Nigeria. This study was undertaken to locate the isolated cases with a
      view to determining their origin. Hb electrophoresis was performed on 4,263
      subjects in Akwa Ibom State in south eastern region of Nigeria. The subjects were
      selected from all the local government areas of the state and were aged 15 years
      and above. They comprised secondary school children, civil servants, farmers and
      fishermen. The results revealed complete absence of Hb C from the upland
      population whereas this was present in the fishing settlement population (6 or
      0.4% Hb AC and one or 0.07% Hb SC subjects). The possible entry points of Hb C
      gene into south eastern Nigeria is discussed.

PMID- 8991234
TI  - Platelet function in patients with sickle cell anaemia in Nairobi.
AB  - From July 1990 to January 1991 we studied platelet functions in 55 indigenous
      Kenyan patients (23 males and 32 females) with sickle cell anaemia (SCA) in
      steady state (SCASS) and in 20 (11 males and 9 females) SCA patients in vaso
      occlusive sickle cell crisis (VSCC). A control group of 50 healthy (23 males and
      27 females) individuals matched for age and sex was also studied. Platelet
      aggregation time to ADP in SCASS (57.2 +/- 39.1) and in VSCC (31 +/- 11.1) were
      more prolonged (p < 0.05) compared to controls (12.7 +/- 5.2). It was also
      significantly more prolonged (p < 0.05) in VSCC than in SCASS. Platelet
      adhesiveness time was 31.1 +/- 13.7 seconds in SCASS, 30.9 +/- 11.1 in VSCC, and
      37.7 +/- 13.0 in controls and was significantly lower in both SCA groups (p <
      0.05) but there was no significant difference between the two SCA groups
      themselves. Clot retraction was 52.8 +/- 6.9 in SCASS, 53.6 +/- 10.7 in VSCC, and
      45.9 +/- 8 in controls and was significantly higher in both SCA groups than in
      controls (p < 0.05). There was no significant difference between the two SCA
      groups themselves. We conclude that platelet function is deranged in indigenous
      Kenyan patients with SCA.

PMID- 8991235
TI  - Comparison of reported and confirmed malaria during pregnancy: findings from
      hospital and community studies in Sudan.
AB  - Hospital case-control and community follow-up studies were conducted to compare
      the results of laboratory confirmed malaria against the reliability of maternal
      reported malaria at time of delivery. The studies were carried out in Sudan in
      Gezira area where malaria is stable and in Sennar area where malaria is unstable.
      In the hospital study, 348 cases were compared with 812 controls. In the
      community study, 275 cases were compared with 1248 controls. Overall, reported or
      confirmed malaria was significantly associated with low birth weight. The results
      were consistent between the hospital and community populations in Wad Medani
      (Gezira) area. However, the association of malaria with low birth weight was
      weaker and inconsistent between the hospital and the community in Sennar area.
      This discrepancy is related to unbalanced exposure to malaria among cases and
      controls in the Sennar area where malaria prevalence is higher among urban than
      among rural populations. The results suggest that maternal history is a
      reasonably accurate method of assessing clinical episodes of malaria during
      pregnancy especially where malaria is stable and therefore justifies presumptive
      treatment of malaria. The unique patterns of malaria transmission in Sennar area
      emphasise the need for through evaluation of local epidemiological factors for
      better malaria control activities.

PMID- 8991236
TI  - Prevalence of human immunodeficiency virus infection: its impact on the
      diagnostic yields in exudative pleural effusions at the Kenyatta National
      Hospital, Nairobi.
AB  - This was a descriptive cross-sectional study carried out at Kenyatta National
      Hospital (KNH), Nairobi, among consecutively admitted adult patients with
      exudative pleural effusions over a one year period. The aim of the study was to
      determine the prevalence of human immunodeficiency virus (HIV) infection in these
      patients and to compare the diagnostic yields from the pleural fluid and pleural
      biopsy between the HIV seropositive and HIV seronegative patients. Sixty six
      patients were studied, with a mean age of 33.8 (+/- SD = 15.6) years and a male
      to female ratio of 1.6:1. Overall, 27 patients(40.9%) were found to be HIV
      seropositive. The commonest cause of exudative pleural effusions, overall, was
      tuberculosis (78.8%) followed by neoplasms (7.6%). Comparing the aetiology of
      exudative pleural effusion in HIV seropositive and HIV seronegative patients,
      tuberculosis was still the commonest cause accounting for 42.3% and 57.7% of the
      cases in each of the groups respectively. Conversely, 42.3% of patients with
      tuberculous pleural effusions were HIV seropositive. There was no significant
      difference in yields from pleural fluid, pleural biopsy culture and histology in
      the diagnosis of tuberculosis in the two patient groups. The only two patients
      with empyema were HIV seropositive and the bacterial isolates were Salmonella
      typhimurium and Pseudomonas aeruginosa. Kaposi's sarcoma was the cause of
      exudative pleural effusion in the one HIV seropositive patient with a malignant
      effusion. The only patient with a parapneumonic effusion was HIV seronegative. No
      fungi were isolated.

PMID- 8991237
TI  - Field trial of combined yellow fever and measles vaccines among children in
      Nigeria.
AB  - The compared tolerance and immunogenecity of yellow fever and measles vaccines
      administered separately or combined were evaluated in Nigerian children aged
      between six to eight and nine to twelve months. The vaccines were well tolerated
      by both age groups of children, however pyrexia which responded to analgesic was
      the commonest post vaccination reaction in all the groups of the vaccinated
      children. Immune response to the vaccines either when given separately or
      combined was excellent in all the vaccinated groups. Antibody titre and
      seroconversion rate were always higher in the group that received the combined
      vaccines together. Our results confirmed that combined yellow fever and measles
      vaccines are safe for children aged between six to twelve months and we therefore
      recommend that yellow fever be incorporated into the EPI programme and be given
      together with measles at the age of nine months.

PMID- 8991238
TI  - Serological evidence of Lyme borreliosis in Africa: results from studies in Dar
      es Salaam, Tanzania.
AB  - Investigations were performed on sera from blood donors, pregnant women, patients
      with polyarthritis and from patients with clinical suspicion of syphilis in Dar
      es Salaam using Borrelia burgdorferi (Bb) flagellar antigen in a second
      generation ELISA test from DAKO A/S, Denmark, for specific IgM or IgG antibodies.
      An IgM and or IgG seropositivity rate of 30/100 (30%), 19/50 (7.2%), 10/20 (50%)
      and 11/20 (55%) was found in sera from the respective groups. These results
      compare with a Bb seroprevalence rate of 4/100 (4%), 1/52 (2%) and 363/5024
      (7.2%) in blood donors, in pregnant women and in patients investigated
      serologically for Lyme borreliosis (Lb) respectively in Bergen, Norway, where
      cases of Lb are detected regularly. The high prevalence of antibodies to Bb
      flagellar antigen in Dar es Salaam, Tanzania where clinical conditions including
      erythema migrans, arthritis, mycocarditis and CNS diseases as well as tickbites
      are found call for further clinical, entomological and laboratory investigations.

PMID- 8991239
TI  - Gram negative bacillary meningitis in infants and children in developing
      countries.
AB  - Gram negative bacillary meningitis (GNBM) in postneonatal infants and children is
      two to three times more common in developed compared to developing countries.
      Other major differences are in the pattern of pathogens (mainly Klebsiella spp
      and Salmonella spp in developing versus E. coli in developed countries) and
      associated conditions (diarrhoeal diseases and malnutrition in developing versus
      neurosurgical and urinary tract abnormalities in developed countries). 12 (11.5%)
      of 104 cases of bacterial meningitis were due to GNB, including Klebsiella spp
      seven, E. coli, two and untyped Coliform spp, three; the age range of patients
      with GNBM was 3-24 months. Among seven completely evaluable patients, six
      presented after seven days of illness, five convulsed on or before admission, and
      six had accompanying respiratory or gastro-enteritic illnesses but none was
      severely malnourished or had associated neurosurgical or urinary tract
      abnormalities. Three patients died, three were discharged with sequelae and one
      without sequelae. The only significant difference between patients with GNBM and
      those with meningitis due to "usual" pathogens was the greater tendency to
      delayed presentation among the former (6/7 patients with GNBM versus 11/36
      "usual" pathogens; p = 0.011); this was also the only striking difference in
      presentation when compared with patients from developed countries. The need for
      further studies, preferably multicentred, and for a revision of the traditional
      combination of gentamicin and ampicillin or chloramphenicol and ampicillin for
      the treatment of GNBM in developing countries is discussed.

PMID- 8991240
TI  - HBsAg ELISA: comparison of serum and uncentrifuged plasma samples dried on filter
      paper.
AB  - To compare the serum and uncentrifuged plasma for hepatitis B surface antigen
      (HBsAg) enzyme linked immuno sorbent assay (ELISA), ninety samples were analysed.
      The study was conducted so that in the field, where no amenities are available
      especially in countries like Pakistan, the separated but uncentrifuged plasma may
      be preserved by spotting on the filter paper for sero-epidemiological studies
      later. It was found that there was no statistically significant difference
      between the serum and uncentrifuged plasma values.

PMID- 8991241
TI  - Migraine headaches in a group of medical students at the Kenyatta National
      Hospital, Nairobi.
AB  - A survey was carried out on 711 medical students from both the medical school and
      the Kenya Medical Training Centre on headaches using a closed ended
      questionnaire. Six hundred and twenty five (88%) of the students reported to have
      at least one episode of headache in the last six months. Two hundred and forty
      (33.8%) of these were classified as migraine using the International Headache
      Society case definition. Seventy (29%) had migraine with aura, the rest being
      migraine without aura. The mean age was 22.7 +/- 5 years with a male to female
      ratio of 1:1.3. The majority of the respondents (43%) had an average of two to
      three headache episodes per month. The major triggering factors for the headache
      were physical activities, emotional disturbance and studying, each occurring in
      21% of the student respondents. It was reported by 43.6% of the respondents that
      there was a member of their nucleus family with a similar headache. Only 40% of
      the respondents had sought medical attention for their headache in the last one
      year. The main reason for not seeking medical services was self medication in 56%
      of those who did not attend medical services. Only 27 (11%) of the respondents
      were currently on medication which consisted of simple analgesics and
      antimalarials. There were only two students who were on specific drugs for
      migraine. The majority of the respondents continued to be inadequately treated
      despite the development of wide range of effective treatment.

PMID- 8991242
TI  - Management of incomplete abortion with manual vacuum aspiration in comparison to
      sharp metallic curette in an Ethiopian setting.
AB  - This institution based case control study emanated from the fact that manual
      vacuum aspiration (MVA) has been recently introduced in Ethiopia and Gandhi
      Memorial hospital is currently serving as the pioneering centre. Abortion is an
      important everyday medicolegal, social, political and public health issue. The
      objectives of the study were to focus on abortion issues, to show that MVA is
      alternative instrument applicable in our setting and to highlight some of the
      determinants that can influence the choice of instruments in the management of
      incomplete abortions of less than 12 weeks of gestation. A total of 1896 patients
      who fulfilled the inclusion criteria underwent evacuation and curettage with MVA
      and SMC during the study period. The main considered variables included socio
      demographic characteristics, service-providers, complications in relation to
      operators and method of surgery, duration of the surgery, patient pain evaluation
      and uterine factors. MVA is found to be equally safe, effective, simple and fast
      set of instruments which can be employed in the management of incomplete
      abortions. Integration of MVA in the medical training is recommended as it is a
      measure which can greatly contribute towards the reduction of maternal morbidity
      and mortality especially in a developing country like ours where resources are
      scare and alternatives are quite limited.

PMID- 8991243
TI  - Traumatic anterior dental injuries in Nigerian preschool children.
AB  - An epidemiological survey of 1,401 preschool children aged one to five years was
      carried out in 21 day care and nursery schools from Ile-Ife, Nigeria to determine
      by sex and age, the prevalence of traumatic injuries to primary incisors and
      canines with their distribution according to type of injuries. The prevalence of
      injuries was 30.8%. No significant difference in prevalence between boys and
      girls was reported. The most common type of injury in the population was enamel
      fracture (66.8%). Most of the children had only one traumatised tooth and
      maxillary central incisors were the most commonly involved teeth in trauma. There
      is need to provide adequate preventive and treatment care in view of the
      consequences on permanent dentition.

PMID- 8991244
TI  - Emerging concepts about the renin angiotensin system: present and future clinical
      applications.
AB  - This review article looks at the emerging concepts about the renin angiotensin
      system. The specific aspects it covers include angiotensin II receptors,
      angiotensin receptor antagonists and alternative enzymatic pathways for the
      conversion of angiotensin I to angiotensin II other than angiotensin converting
      enzyme. The review, additionally, looks at the current and future clinical
      applications of the above concepts.

PMID- 8991245
TI  - Radiotherapy in cancer management at Mulago Hospital, Kampala, Uganda.
AB  - Five hundred and seven cancer patients who received radiotherapy using the newly
      upgraded facilities at the Mulago Hospital over a 16 month period following the
      inception of the services are reviewed. Previously available facilities had been
      limited to teletherapy using only a 300 KV orthovoltage X-ray machine which had
      proved inadequate to cope with the current needs at the department. The
      International Atomic Energy Agency (IAEA) in Vienna recently upgraded the
      available services through the provision of facilities for cobalt-60 teletherapy,
      brachytherapy and computerised treatment planning and dosimetry as well as
      providing training for all cadres of the radiotherapy department. We review the
      impact of this new service on the referral pattern and types of patients who
      received radiotherapy since inception. Over 60% of all the patients were women
      who presented with carcinoma of the cervix and breast. Apart from the apparent
      increase in cases of cervical carcinoma, the current AIDS pandemic in Uganda did
      not appear to reflect any increase in the incidence of other AIDS-related cancers
      such as Kaposi's sarcoma and non-Hodgkins lymphomas treated at the department.
      The need for more patients and earlier referrals to the department is stressed in
      order to maximise the use of the improved radiotherapy services.

PMID- 8991246
TI  - Kidney transplantation: recent medical experiences from the Kenyatta National
      Hospital, Nairobi.
AB  - Renal transplantation is not readily available in the majority of countries in
      Africa. It is expensive and difficult to sustain on the meagre funds allocated to
      health. We report our short experience with fifteen living donor recipients
      followed in our unit for at least 24 months, range 26 - 48 (mean 35 months) post
      transplantation. The donors and recipients were mostly young adults with mean
      ages of 36.7 years and 32.6 years respectively. The majority of the donors and
      recipients were males. The donors in most cases were siblings. Within this time,
      one graft has been lost at one year and the patient restarted on haemodialysis.
      Three patients died, two within the first year, the third at 23 months after
      transplantation, all with functioning grafts. The one year graft and patient
      survival rates were 93% and 86.6% respectively. The second year graft survival
      rates remained at 93% and the patients survival rate 80%. The nature and
      frequency of complications seen in these patients is comparable to those in other
      centres. Of all medical complications, bacterial infections contributed 69.4% of
      all infections. Cardiovascular complications comprised 31.25% of the
      complications. Hypertension seen in 85.5% of the patients accounted for 65% of
      the cardiovascular complications. Acute rejections were common and occurred in
      seven patients. Transplantation is a viable mode of renal replacement therapy
      (RRT) in our environment. The practice should be supported to make it more
      readily available to the many young end stage renal failure (ESRF) patients.

PMID- 8991247
TI  - Caesarean section deliveries at Tikur Anbessa Teaching Hospital, Ethiopia.
AB  - This prospective hospital-based study was done at Tikur Anbessa Teaching Hospital
      (TATH) between July 1991 and July 1992 in order to obtain base-line data on the
      rates of caesarean section, pregnancy out-come, major indications for caesarean
      and caesarean section complications. Out of a total of 3237 deliveries conducted
      during the study period, 318(10%) were caesarean section. The leading or the
      major indication for abdominal deliveries were: repeat caesarean section,
      103(32.4%), cephalo-pelvic disproportion, 93(29.2%), placenta previa and abruptio
      placentae 40(12.6%). Age ranged from 15-40 years, 58(18.2%) were women under the
      age of 20, and 182(57%) were between 20 and 30 years of age which is the safest
      period to bear children. Eighty one (25%) of the mothers were primiparae,
      158(50%) were between para one and para four, 79(25%) were grand multiparae.
      Seventy six (24%) of the cases were not registered for antenatal care in any
      health institutions. Two hundred and fifteen (67.6%) of the mothers had primary
      caesarean section. The chance of repeat caesarean section was statistically
      significant (P < 0.001). Fifty seven (18%) had elective caesarean section and 261
      (82%) were emergency caesarean section. On eight (2.5%) of the patient, obstetric
      hysterectomy was performed. There were five maternal deaths among the caesarean
      section cases. The main cause of maternal death was failure to control bleeding
      during the caesarean section. These were preventable deaths in experienced hands.
      There were nine (2.8%) stillbirths and 15(4.7%) early neonatal deaths. A foetal
      wastage of 24(7.5%) was noted in the study. The mean birthweight among booked
      caesarean section were 3108 grams and unbooked caesarean section were 2991 grams.
      The major obstetric complications in the cases were antepartum haemorrhage, and
      34(11%), pregnancy induced-hypertensive disorder, 32(10%). Sixty one (19%) had
      blood transfusion. The blood loss was significantly more in operations done by
      residents compared to consultants even using the most crude measurement as
      estimated by the operator at the time.

PMID- 8991248
TI  - Landry Guillain-Barre-Strohl syndrome in pregnancy: case report.
AB  - Landry-Guillain-Barre-Strohl Syndrome (LGBS) is a rare occurrence in pregnancy
      with only 38 previously reported cases in the literature. A case of a 26 year old
      Ghanaian woman who presented at thirty weeks gestation with limb weakness, facial
      diplegia, dysarthria, dysphagia and CSF cytoalbuminic dissociation and who made
      complete recovery before delivery of a normal full term baby is described. This
      is the thirty ninth reported case of LGBS in pregnancy in the literature and the
      first reported case from Black Africa. It is the third reported case of full
      recovery before delivery. The aetiology, diagnosis and management of LGBS is
      briefly reviewed.

PMID- 8991249
TI  - An unstable fracture dislocation of the hip due to an occult free intra-articular
      fragment: case report.
AB  - A case report is presented of a 53 year old man who presented with posterior
      dislocation of the hip after a road traffic accident. Initial management by
      closed reduction failed due to presence of an occult free intra-articular
      fragment. This fragment was not visualised on plain A-P and lateral X-ray views.
      The cause of the failed closed reduction was eventually detected by CT scan. Open
      reduction and removal of the bone fragment was done and the hip remained stable
      thereafter. It is concluded that plain X-rays are not adequate in the diagnosis
      of free intra-articular bone fragments within the hip joint and CT scanning is
      advised for accurate detection of such occult bine fragments.

PMID- 8991250
TI  - Invasive squamous cell carcinoma of the limbus: case report.
AB  - Limbal squamous cell carcinoma is uncommon worldwide. Its early stages of
      presentation may look like the commoner limbal mass, pterygium. We report a case
      of invasive squamous cell carcinoma which was initially diagnosed as inflamed
      pterygium. A high index of suspicion is required to prevent delay in the
      diagnosis of an invasive condition that can destroy the eye completely. Treatment
      modalities are reviewed.

PMID- 8991251
TI  - A guide to facilitating consumer choice.
AB  - Some purchasers and policymakers are advocating models that offer consumers a
      choice of health plans as a way to help them choose a plan that best meets their
      needs and to create incentives for health plans to compete on the basis of
      efficiency, quality, and service. A review of six consumer-choice models
      indicates that these objectives can be met if purchasers (1) create a level field
      for comparison through standardized benefits and structured enrollment processes;
      (2) offer a limited number of plans that meet appropriate selection criteria; (3)
      provide comprehensive, objective, and reliable consumer information; (4) support
      the process with education; and (5) hold plans accountable through uniform
      reporting of performance data.

PMID- 8991252
TI  - Consumer's information needs: results of a national survey.
AB  - A national survey conducted in 1995 found that a disturbingly high percentage of
      Americans do not understand the basic elements of health plans and that people
      want much more information, particularly about the physicians in the plans and
      the range of services that are covered. Their most important concern when
      selecting a health plan is the quality of physicians in the plan, followed by the
      courtesy of doctors and staff and the freedom to choose their own doctors and
      hospitals.

PMID- 8991254
TI  - The market comes to Medicare: adding choice and protections.

PMID- 8991253
TI  - What information do consumers want and need?
AB  - This paper reviews information from surveys and focus group studies about how
      consumers define high-quality care and the types of information they want when
      making decisions about which health plan to join. The authors also interviewed
      consumer advocacy groups and persons responsible for disseminating health plan
      information to Medicare enrollees in various types of managed care plans to learn
      about the types of plan information that Medicare enrollees most often request.
      They describe the types of information that should be made available to consumers
      and the challenges involved in making this information understandable and useful.

PMID- 8991255
TI  - Managed care and physician/hospital integration.
AB  - This paper examines the extent to which hospitals and physicians use new
      organizational structures designed to facilitate contracting with managed care
      firms and the extent to which this use is associated with managed care revenue.
      The data come from a nationally representative sample of 1,495 U.S. community
      hospitals responding to a 1993 survey about different organizational structures.
      The results indicate that only 23.3 percent of hospitals participate in at least
      one form. Hospitals with more than 15 percent of revenues from managed care are
      twice as likely to participate and favor forms that provide tighter linkages with
      physicians.

PMID- 8991256
TI  - Length-of-stay after delivery: managed care versus fee-for-service.

PMID- 8991257
TI  - Access to care in HMOs and traditional insurance plans.

PMID- 8991258
TI  - Downsizing the hospital nursing workforce.

PMID- 8991260
TI  - Proving the policy wonks wrong.

PMID- 8991259
TI  - What is driving health system change?
AB  - Socially amoral economic forces now drive health system change. The authors,
      assisted by a panel of experts on employers, health plans, providers, and
      consumers, discuss current drivers such as (1) employers' price-focused
      purchasing, without good quality/value measures; (2) health plans' growing
      successes and market clout; (3) providers declining prospects and fears about
      their future; and (4) consumers' worries about less choice. Future influences
      will include Medicare reforms, better information, and pro-consumer regulation of
      managed care, as well as rising social distress. The health system's future is
      now open for resolution in an evolving, imperfect market.

PMID- 8991261
TI  - Predicting future health system change.

PMID- 8991262
TI  - A different health care world than expected.

PMID- 8991263
TI  - Whither quality?

PMID- 8991264
TI  - Health system change: skirmish or revolution?

PMID- 8991265
TI  - Chaotic, shifting relationships of purchasers, plans, and providers.

PMID- 8991266
TI  - Rationalizing the fraud and abuse statute.

PMID- 8991267
TI  - The fraud and abuse statute: rationalizing or rationalization?

PMID- 8991268
TI  - Do nonprofit hospitals pay their way?
AB  - Using 1988 and 1991 data from nonprofit voluntary hospitals in California, we
      find that the vast majority of nonprofit hospitals provide community dividends in
      excess of the tax subsidies they receive. However, nearly 20 percent of nonprofit
      hospitals do not meet this standard. Further, those hospitals that do not meet
      the standard tend to not meet the standard over time. We recommend more explicit
      identification of the community dividends expected in return for special tax
      treatment and more explicit accounting on the part of nonprofit hospitals.

PMID- 8991269
TI  - The home health visit: an appropriate unit for Medicare payment?
AB  - To contain costs and increase incentives for efficient provision of care,
      prospective payment methods are being proposed for Medicare home health services.
      Although a shift to per episode payment is much discussed, the methods rely on
      the home health visit as a fundamental building block in setting rates and
      ceilings. Some propose setting fixed per visit prices in the interim until
      episode payment can be developed. Findings from the evaluation of a Health Care
      Financing Administration (HCFA) demonstration of per visit payment suggest that
      this could shorten to the length of visits provided to Medicare beneficiaries.
      Because of home health agencies' discretion over visit length, we question
      whether the visit is the appropriate basic unit for developing prospectives
      payment methods for Medicare home health.

PMID- 8991270
TI  - High hospital admission rates and inappropriate care.
AB  - This study tests whether the rate of inappropriate hospital admissions is high in
      areas with high medical admission rates. Seventy small geographic areas were
      formed by grouping Massachusetts ZIP codes by similarity of hospital use.
      Appropriateness of hospital admission was measured both by applying the
      Appropriateness Evaluation Protocol and by applying physicians' judgment to the
      medical records of patients age sixty-five and older who were admitted for
      treatment of a medical condition in 1990-1992. No relationship between hospital
      admission rate and inappropriate admission rate was found, which calls into
      question the common assumption that areas with higher hospital use have more
      inappropriate use of hospital care.

PMID- 8991271
TI  - On the appropriateness of small-area analysis for cost containment.

PMID- 8991272
TI  - The view from managed care pharmacy.
AB  - This stratified, national telephone survey of fifty-one managed care
      organizations concerns the perspectives of managed care pharmacy directors on
      pharmacoeconomics, disease management, and the roles of the pharmaceutical
      industry and the Food and Drug Administration (FDA). Respondents rated clinical
      effectiveness assessments as most useful, cost-effectiveness assessments second,
      and quality-of-life assessments as least useful. Peer-reviewed and industry
      literature were rated as equally important for decision making. Most plans would
      consider establishing a partnership with a drug company for disease management,
      if they have not already done so. Most plans (76 percent) support some form of
      FDA regulation of pharmacoeconomic claims. Conversely, 69 percent favor either no
      regulation (24 percent) or less stringent regulation (45 percent) than exists
      today.

PMID- 8991274
TI  - Health plan conversions: the view from Blue Cross of California.

PMID- 8991273
TI  - Cost differences among women's primary care physicians.
AB  - A secondary analysis of data from the 1987 National Medical Expenditure Survey
      revealed that women with distinct demographic and socio-economic characteristics
      identify different physician specialty groups as their usual source of care. The
      use of certain physician groups for primary care resulted in higher rates of use
      and expenditures, particularly for younger women. Identifying an internist,
      rather than a family/general practitioner or an obstetrician/gynecologist, as a
      usual source of care placed one at higher odds of making more visits and
      incurring higher total outpatient costs.

PMID- 8991275
TI  - The limits of the hospital.

PMID- 8991276
TI  - A new payment method for inpatient care.

PMID- 8991277
TI  - Is cost the primary cause of declining hospital days?

PMID- 8991278
TI  - Taking issue with a 'heretical hypothesis'.

PMID- 8991279
TI  - Payment versus pricing: which is the central issue?

PMID- 8991280
TI  - Lessons in Medicaid managed care.

PMID- 8991281
TI  - Impact of market change on the physician workforce.

PMID- 8991282
TI  - Market competition and growth of hospital staff.

PMID- 8991283
TI  - The calpain-calpastatin system in rheumatoid arthritis.

PMID- 8991284
TI  - Oral cytokine administration.

PMID- 8991285
TI  - Immune responses to parasites: the art of distinguishing the good from the bad.

PMID- 8991286
TI  - The influence of virus structure on antibody responses and virus serotype
      formation.

PMID- 8991287
TI  - Could endogenous self-peptides presented by dendritic cells initiate rheumatoid
      arthritis?

PMID- 8991288
TI  - Regulating integrin-mediated adhesion: one more function for PI 3-kinase?

PMID- 8991289
TI  - Do macrophages kill through apoptosis?
AB  - Macrophages can kill target cells independent of conventional immune specificity.
      Based on a re-examination of literature three decades old and recent experiments,
      Antonios Aliprantis and colleagues propose that macrophages kill target cells by
      inducing apoptosis. For this purpose, macrophages employ a selection of pro
      apoptotic mediators including reactive oxygen and nitrogen species and tumour
      necrosis factor alpha.

PMID- 8991291
TI  - Chimerism and transplantation tolerance: cause and effect.

PMID- 8991290
TI  - The lost chord: microchimerism and allograft survival.

PMID- 8991292
TI  - Evolution of allorecognition?

PMID- 8991293
TI  - Forensic and legal implications in clinical practice: a master class commentary.

PMID- 8991294
TI  - Illusory safeguards: legitimizing distortion in recall with guidelines for
      forensic hypnosis--two case reports.
AB  - Two amnesic automobile accident victims remembered the information needed for
      their ongoing lawsuits during hypnosis. Meeting the recording requirements of the
      Hurd safeguards led to the admission of hypnotically influenced testimony in
      court in one case, whereas failure to record led to exclusion in the other. In
      both cases, closed-head trauma almost certainly prevented long-term memory
      consolidation. Thus adherence to guidelines for forensic hypnosis legitimized
      distortions in recall instead of preventing them. Hypnosis used to facilitate
      hypermnesia alters expectations about what can be remembered, makes memory more
      vulnerable to postevent information, and increases confidence without a
      corresponding increase in accuracy. Distortion of recall is an inherent problem
      with the use of hypnosis and hypnotic-like procedures and cannot be adequately
      prevented by any set of guidelines.

PMID- 8991295
TI  - Depersonalization and derealization during panic and hypnosis in low and highly
      hypnotizable agoraphobics.
AB  - The primary aim of the present study was to investigate the association between
      spontaneous experiences of depersonalization or derealization (D-D) during panic
      states and hypnosis in low and highly hypnotizable phobic individuals.
      Secondarily, the association among level of hypnotizability, capacity for
      imaginative involvement, and severity of phobic complaints was also assessed.
      Sixty-four patients with panic disorder with agoraphobia according to the DSM-III
      R (American Psychiatric Association, 1987) criteria participated in the study.
      Proneness to experience D-D during hypnosis was positively related to
      hypnotizability, but only for agoraphobic patients who had already experienced
      these perceptual distortions during panic episodes. Correlations of level of
      hypnotizability and capacity for imaginative involvement with severity of
      agoraphobic complaints were not significant. These findings suggest that
      hypnotizability may be a mediating variable between two different, although
      phenotypically similar, perceptual distortions experienced during panic states
      and hypnosis. Implications for both theory and clinical practice are discussed.

PMID- 8991296
TI  - The effects of hypnosis, context reinstatement, and anxiety on eyewitness memory.
AB  - The effects of hypnosis, context reinstatement, and motivational instructions on
      accuracy of recall for factual information and facial recognition accuracy
      following a stressful event were assessed. None of the three techniques had a
      significant effect on factual memory or susceptibility to suggestion as assessed
      by true-false and multiple-choice tests. However, participants high in hypnotic
      susceptibility showed somewhat better memory on the true-false test, and hypnosis
      affected performance on the two photograph line-ups. In addition, hypnosis
      appeared to enhance facial recognition accuracy for participants who were low in
      anxiety, but not for those high in anxiety. Finally, there was evidence of a
      curvilinear relationship between self-reported anxiety at time of retrieval and
      facial recognition accuracy.

PMID- 8991297
TI  - Hypnotizability, the dissociative experiences scale, HGSHS: A amnesia, and
      automatic writing: is there an association?
AB  - The present study examined whether participants (N = 112) selected on the basis
      of high and low dissociative ability (Dissociative Experiences Scale [DES];
      Bernstein & Putnam, 1986), high and low/simulating hypnotizability (Harvard Group
      Scale of Hypnotic Susceptibility, Form A [HGSHS:A]; Shor & Orne, 1962), and past
      performance on the HGSHS:A amnesia item differentially passed an automatic
      writing suggestion administered during a follow-up experiment. Results from a
      loglinear analysis supported a single main effect for hypnotizability. Low
      hypnotizable, simulating participants were more than six times as likely to pass
      the automatic writing suggestion than high hypnotizable participants. Results
      found dissociation status and past performance on an ostensibly dissociative
      suggestion (i.e., amnesia) to be independent of passing the automatic writing
      suggestion. Findings are discussed in light of other research regarding the
      relation between the DES and hypnotizability.

PMID- 8991298
TI  - Introduction to the special section on the development of theoretically coherent
      alternatives to the DSM system.
AB  - This introduction outlines a series of articles in the Journal of Consulting and
      Clinical Psychology that represent a theoretically organized challenge to the
      Diagnostic and Statistical Manual of Mental Disorders (DSM; e.g., 4th ed.;
      American Psychiatric Association, 1994). A criticism of the DSM is offered on the
      basis that a taxonomy based on inadequately explicated theory has not been and
      cannot be a successful basis for a scientific research program. The special
      section offers examples of behaviorally based alternative ways of understanding
      behavior of clinical interest. Others are invited to develop taxonomies based on
      different theoretically coherent foundations.

PMID- 8991299
TI  - Models of scientific progress and the role of theory in taxonomy development: a
      case study of the DSM.
AB  - The proliferation of categories in recent editions of the Diagnostic and
      Statistical Manual of Mental Disorders (e.g., 4th ed.; DSM; American Psychiatric
      Association, 1994) is discussed as an indication that the underlying
      classification scheme is inadequate and unlikely to produce the scientific
      progress originally envisioned. In any nosological system, it eventually becomes
      necessary to reduce the number of categories by an organizing theory that
      describes the fundamental principles underlying the taxonomy. The DSM has put
      itself in an awkward position by claiming to be atheoretical. Although taking
      such a tack had historical advantages to promote the acceptability of the 3rd
      edition of the DSM, it now limits the progression of science. It is argued that
      the DSM should not be used as the basis for guiding scientific research programs
      because it emphasizes primarily behavioral topography rather than providing an
      explicit theory that would allow for an evaluation of scientific progress.
      Theoretically driven taxonomies should be allowed to compete on the basis of how
      successful they are at achieving their specified goals that might include
      illuminating etiology, course, and response to treatment. Such systems are not
      likely to attend primarily to behavioral topography alone and would probably
      organize behavior differently than the current categorical syndromes seen in the
      4th edition of the DSM.

PMID- 8991300
TI  - Aristotle, Galileo, and the DSM taxonomy: the case of schizophrenia.
AB  - With the diagnosis schizophrenia used as an example throughout, the fourth
      edition of the Diagnostic and Statistical Manual of Mental Disorders's (American
      Psychiatric Association, 1994) approach to psychopathologic taxonomy is subjected
      to critical analysis as representing a fundamentally Aristotelian conception of
      the phenomena of mental disorders. This approach is contrasted, in the manner
      suggested by Kurt Lewin's early writing on the subject, with the Galileian mode
      of thought, emphasizing the dynamic causal matrix in which behavior occurs. Some
      of the positive implications of an altered view of the problem of taxonomy within
      the latter perspective are drawn out, and brief suggestions are made as to
      directions for the future.

PMID- 8991301
TI  - A logical functional analysis of reinforcement-based disorders: alcoholism and
      pedophilia.
AB  - This article discusses a nomothetic functional strategy, termed logical
      functional analysis, as an approach to the refinement of the structural
      diagnostic categories of the Diagnostic and Statistical Manual of Mental
      Disorders (e.g., 4th ed.; DSM-IV; American Psychiatric Association, 1994). As
      heterogeneous diagnostic categories are more the norm than the exception in the
      DSM-IV, an argument is made for the identification of homogenous subgroups within
      diagnostic classes based on functional principles. Outlines of a logical
      functional analysis for 2 reinforcement-based disorders, alcoholism and
      pedophilia, are presented. The outlines show how topographically similar behavior
      patterns can serve different functions that are important to consider when making
      treatment decisions. The logical functional analysis is a strategy that helps
      practitioners to identify motivational conditions, antecedents, consequences, and
      concomitant behavioral repertoires associated with a given disorder. It also
      provides guidance for the selection of intervention strategies.

PMID- 8991302
TI  - Experimental avoidance and behavioral disorders: a functional dimensional
      approach to diagnosis and treatment.
AB  - Syndromal classification is a well-developed diagnostic system but has failed to
      deliver on its promise of the identification of functional pathological
      processes. Functional analysis is tightly connected to treatment but has failed
      to develop testable, replicable classification systems. Functional diagnostic
      dimensions are suggested as a way to develop the functional classification
      approach, and experiential avoidance is described as 1 such dimension. A wide
      range of research is reviewed showing that many forms of psychopathology can be
      conceptualized as unhealthy efforts to escape and avoid emotions, thoughts,
      memories, and other private experiences. It is argued that experiential
      avoidance, as a functional diagnostic dimension, has the potential to integrate
      the efforts and findings of researchers from a wide variety of theoretical
      paradigms, research interests, and clinical domains and to lead to testable new
      approaches to the analysis and treatment of behavioral disorders.

PMID- 8991303
TI  - Diagnosis of personality disorder: a radical behavioral alternative.
AB  - From a radical behavioral perspective, a single, diagnostic system is unlikely to
      serve diverse purposes. Instead, ideal diagnostic systems should be developed to
      serve specific purposes. For example, the crucial proof required of a
      classification system designed to improve the outcome of psychosocial
      intervention would be that it enhance the clinician's influence on processes
      associated with client change. This means, in turn, that the change processes
      must be known or theoretically specified. As an illustration of this general
      approach to diagnostic classification, a specific behavioral theory is used to
      articulate processes of change in psychotherapy. The Axis II of the Diagnostic
      and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric
      Association, 1994) is then evaluated with respect to its ability to enhance
      clinicians' influence of these processes, found problematic, and an alternative
      classification criterion is proposed.

PMID- 8991304
TI  - DSM-IV and disorders of childhood and adolescence: can structural criteria be
      functional?
AB  - The structural, descriptive basis of the diagnostic categories outlined in the
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American
      Psychiatric Association, 1994) is contrasted to a system of functional analysis,
      with regard to (a) clinical diagnosis, (b) target behavior identification, (c)
      treatment design, (d) treatment evaluation, and (e) clinical research. It is
      noted that structural classification is a useful starting point for these
      activities but that functional analysis has greater utility for target behavior
      identification and treatment design by giving consideration to antecedent and
      consequent events, skills repertoires, response interrelations, and support
      systems. Examples of melding structural classification and functional analytic
      systems are provided with reference to certain childhood disorders: mental
      retardation, disruptive behavior disorders, and anxiety disorders.
      Recommendations are made for an elaboration of the DSM axes to include (a)
      psychosocial and environmental resources and deficits, and (b) idiographic case
      analysis. It is suggested that these axes will assist in systematizing functional
      analysis and making it more accessible to all clinicians and researchers.

PMID- 8991305
TI  - Causes and consequences: individual distress in the context of couple
      interactions.
AB  - The covarying relationship between individual distress and couple interactions
      provides justification for developing a system to classify couple interactional
      behaviors. This system is proposed as an alternative to the Diagnostic and
      Statistical Manual of Mental Disorders (e.g., 4th ed.; DSM-IV; American
      Psychiatric Association, 1994) system, whose problems include reliance on linear
      models of causality, atheoretical classification of individual syndromes, and
      poor predictive validity and treatment utility. These difficulties may be
      resolved by using an alternative classification model of couple interactions, at
      least for many distressed individuals and couples. An example of a model for
      classifying couple interactions (including distressed individual behavior) is
      presented. The potential benefits of theoretical consistency, implied treatment
      matching strategies, increased predictive validity and enhanced treatment utility
      of such an alternative classification system are discussed, along with guidelines
      for the further development and testing of couple interaction classification
      alternatives to the DSM nosology.

PMID- 8991306
TI  - Introduction to the special section on structural analysis of social behavior.
AB  - The structural analysis of social behavior (SASB) model dissects interpersonal
      and intrapsychic events into 3 underlying dimensions: (a) focus (on other, on
      self with other, and on self with self): (b) affiliation (love vs. hate); and
      (c), interdependence (enmeshment or dominance-submission vs. differentiation or
      emancipate-separate). Accompanied by predictive principles (similarity,
      opposition, complementarity, introjection, antithesis), the model can
      operationalize important aspects of a wide range of psychological events.
      Questionnaires, coding systems, and software permit the SASB model to be applied
      in a wide array of clinical and research contexts. It has been used by people of
      divergent theoretical persuasions including the interpersonal, cognitive
      behavioral, client-centered, psychoanalytic, expressive, family, and group
      approaches. In this article, the model and its predictive principles are
      reviewed, along with examples of research, clinical, and theoretical
      applications. The articles in this section provided examples of especially
      creative and appropriate uses.

PMID- 8991307
TI  - Varieties of transference patterns in psychotherapy.
AB  - This investigation explored the nature of transference of interpersonal patterns
      in patients' psychotherapy narratives. The relation between interpersonal
      patterns with significant others in a patient's life and the pattern with the
      therapist early in treatment was examined. Cluster analysis was used to
      categorize similar relationships for each of 35 patients. Many patients revealed
      multiple interpersonal themes in their relationship narratives. Furthermore,
      these interpersonal themes correlated significantly with the interpersonal
      pattern extracted from narratives told about the therapist for many of the
      patients who discussed the therapeutic relationship during therapy. However, the
      interpersonal pattern evident in the relationship with the therapist was not
      necessarily the most pervasive pattern exhibited in the narratives about
      significant others.

PMID- 8991308
TI  - Family processes and risk for externalizing behavior problems among African
      American and Hispanic boys.
AB  - This study examined the relationship between family processes and risk for
      externalizing behavior problems among urban African American and Hispanic youth.
      The structural analysis of social behavior was used to code family interactions.
      Results indicate that high-risk boys were more submissive and less warm than low
      risk boys. When they did assert themselves, high-risk boys tended to do so in a
      hostile manner. Parents of high-risk boys were more punitive and less nurturant
      than parents of low-risk boys. Regardless of risk status, African American boys
      were more assertive than Hispanic boys and African American parents were less
      controlling than Hispanic parents. These findings complement previous research on
      the development of antisocial behavior by highlighting the role of the adolescent
      in family processes.

PMID- 8991309
TI  - Relationship of social perceptions and self-concept in bulimia nervosa.
AB  - Although numerous studies have examined the families of bulimic individuals, none
      have explicitly addressed how family factors relate to self-concept among
      patients with bulimia. This study used L. Benjamin's' structural analysis of
      social behavior (1974) rating scales to assess how perceptions of parental
      relationships relate to self-concept. The results indicate that female patients
      with bulimia perceive both parents as hostilely disengaged. Furthermore, the self
      concepts of patients with bulimia were significantly associated with perceptions
      of paternal attack/friendliness, which differentiated them from control
      participants. The results are discussed in terms of the possible relations
      between family factors and self-concept in bulimia.

PMID- 8991310
TI  - Identity and Introject in dissociative disorders.
AB  - The structural analysis of social behavior (SASB) shows promise for
      systematically examining identity issues in clinical populations. In this study,
      identity is assessed with the SASB in a sample of women with dissociative
      disorder (n = 25) and a nonpatient clinical contrast group (n = 25). The SASB
      Introject--a multivariate measure of identity--effectively differentiated the 2
      samples. Despite greater self-directed hostility than the clinical contrast
      group, dissociative disorder patients showed lower levels of intrapsychic
      conflict. Implications for further research on identity and psychopathology are
      discussed.

PMID- 8991311
TI  - Articulating subtype differences in self and relational experience among
      alcoholic men using structural analysis of social behavior.
AB  - L. Benjamin's (1984) structural analysis of social behavior (SASB) system was
      used as the organizing framework within which to characterize the phenomenology
      of self and other relationship experience among subtypes of alcoholic men. Within
      the context of a community-based study of psychopathology, groups of antisocial
      alcoholic (AAL), nonantisocial alcoholic (NAAL), and nonalcoholic (control) men
      completed ratings of their introject (self-concept) and spousal experience. Group
      differences in demography and psychopathology provided strong support for subtype
      variations among alcoholic men that could not be attributed to global differences
      in adaptive functioning. SASB data showed consistency in circumplex ordering
      across the groups in ratings of self-experience and in ratings of the spousal
      relationship. AAL men were the most self-neglecting, blaming, and least trusting,
      and control men were the most relationally connected, with NAAL men falling in
      between. Despite the importance of the subtyping distinction, in some areas,
      alcoholism, regardless of subtype, was the core differentiating factor.

PMID- 8991312
TI  - Structural analysis of families with a polydrug-dependent, bulimic, or normal
      adolescent daughter.
AB  - This study compared perceived relationships and interaction patterns among 44
      families with externalizing (polydrug-dependent), internalizing (bulimic), or
      normal adolescent daughters. Data from L.S. Benjamin's (1974) structural analysis
      of social behavior rating scales and observational coding system were subjected
      to a pattern analysis of effect sizes. Results revealed that families of polydrug
      dependent girls were less well attached and less autonomous than were families of
      daughters with bulimia who were, in turn, less attached and autonomous than
      controls. Observed interactions also showed that parents of drug-dependent
      teenagers communicated a mixed message of blaming the daughter while pseudo
      affirming her. The findings were interpreted as evidence for specific
      disturbances in the critical elements of attachment and autonomy in both clinical
      disorders, with more pronounced and pervasive problems in the families of
      polydrug-dependent girls.

PMID- 8991313
TI  - Structural analysis of social behavior as a common metric for programmatic
      psychopathology and psychotherapy research.
AB  - This article describes the use of Structural Analysis of Social Behavior (SASB;
      L. Benjamin, 1974) as applied to programmatic psychodynamic-interpersonal
      psychotherapy research. SASB fosters cumulative, theory-driven research by
      permitting problem-treatment-outcome (PTO) congruence--the conceptualization and
      measurement of patients' problems, treatment processes, and outcome in a common
      metric. In this explanation of the principle of PTO congruence, the following are
      discussed: a general model of interpersonal psychopathology and etiology, SASB
      based assessment devices for measuring early history and formulating presenting
      problems, empirical studies of interpersonal process in therapy, the relationship
      between manual-guided training and interpersonal process, and the assessment of
      outcome. A generic interpersonal model of psychotherapy is proposed that
      theoretically links all of these elements. Finally, the use of these SASB-based
      models for cross-theory integrative research from a common-factors approach is
      discussed.

PMID- 8991314
TI  - Characteristics of effective therapists: further analyses of data from the
      National Institute of Mental Health Treatment of Depression Collaborative
      Research Program.
AB  - Analyses of the data of the National Institute of Mental Health-sponsored
      Treatment of Depression Collaborative Research Program have primarily examined
      the effects of types of treatment and patient characteristics on outcome, but
      scant attention has been directed toward evaluating the contributions of the
      therapist. With an aggregate of residualized therapeutic change scores of the 5
      primary outcome measures for each patient at termination as an overall measure of
      improvement, an average therapeutic effectiveness measure was derived for each of
      the 28 therapists based on the outcome of the patients they saw in active
      treatment. The distribution of the therapists was divided into thirds, and
      comparisons indicate that more effective therapists are more psychological
      minded, eschew biological interventions (i.e., medication and electroconvulsive
      therapy) in their ordinary clinical practice, and expect outpatient treatment of
      depression to take longer than did moderately and less effective therapists.

PMID- 8991315
TI  - Measuring diagnostic agreement.
AB  - Diagnostic agreement tests the reliability and concordance of diagnostic systems.
      The introduction of measures of agreement with reputations for baserate
      independence (e.g., Yule's Y and Q), and new studies occasioned by the
      publication of the Diagnostic and Statistical Manual of Mental Disorders (4th
      ed.; DSM-IV; American Psychiatric Association, 1994) and the International
      Classification of Diseases--10 (ICD-10; World Health Organization, 1992) make it
      necessary to study the relationship of illness baserates to measures of
      agreement. Testing diagnostic concordance for diagnoses of drug dependence from
      the third edition of the DSM (American Psychiatric Association, 1980) versus DSM
      IV diagnoses of drug dependence under 3 baserate conditions, it was found that
      Yule's Y and Q proved as vulnerable to differences in baserates as kappa or
      percent agreement and that specificity covaried with baserate rather than being
      fixed, as most theoretical discussions assume. The uncritical use of Y and Q,
      therefore, is likely to lead to optimistic interpretations of agreement. Kappa
      should be preferred for most purposes, although an adjustment to the
      computational formulas for Y and Q is presented that can diminish their positive
      bias.

PMID- 8991316
TI  - Random versus nonrandom assignment in controlled experiments: do you get the same
      answer?
AB  - Psychotherapy meta-analyses commonly combine results from controlled experiments
      that use random and nonrandom assignment without examining whether the 2 methods
      give the same answer. Results from this article call this practice into question.
      With the use of outcome studies of marital and family therapy, 64 experiments
      using random assignment yielded consistently higher mean post-test effects and
      less variable posttest effects than 36 studies using nonrandom assignment. This
      difference was reduced by about half by taking into account various covariates,
      especially pretest effect size levels and various characteristics of control
      groups. The importance of this finding depends on (a) whether one is discussing
      meta-analysis or primary experiments, (b) how precise an answer is desired, and
      (c) whether some adjustment to the data from studies using nonrandom assignment
      is possible. It is concluded that studies using nonrandom assignment may produce
      acceptable approximations to results from randomized experiments under some
      circumstances but that reliance on results from randomized experiments as the
      gold standard is still well founded.

PMID- 8991317
TI  - Emotion-abstraction patterns in verbatim protocols: a new way of describing
      psychotherapeutic processes.
AB  - The goal of the study was to develop a computer-aided system that is able to
      identify key moments in transcripts from psychoanalytic sessions and to provide
      an adequate theory of change. The term key moment refers to 1 or more sessions of
      a treatment or to segments of a session that are seen as clinically important and
      often considered to be a turning point or breakthrough and that mirror points of
      insight as they occur in the course of the psychotherapeutic process. It will be
      shown that patterns built of combinations of the content analysis variable
      "emotion tone" and "abstraction" allow for describing therapeutic cycles
      including key moments. The method is shown successfully for a single case and for
      a sample of improved and not improved patients.

PMID- 8991318
TI  - How interchangeable are different estimators of effect size?
AB  - The computation of effect sizes is a key feature of meta-analysis. In treatment
      outcome meta-analyses, the standardized mean difference statistic on posttest
      scores (d) is usually the effect size statistic used. However, when primary
      studies do not report the statistics needed to compute d, many methods for
      estimating d from other data have been developed. Little is known about the
      accuracy of these estimates, yet meta-analysts frequently use them on the
      assumption that they are estimating the same population parameter as d. This
      study investigates that assumption empirically. On a sample of 140 psychosocial
      treatment or prevention studies from a variety of areas, the present study shows
      that these estimates yield results that are often not equivalent to d in either
      mean or variance. The frequent mixing of d and other estimates of d in past meta
      analyses, therefore, may have led to biased effect size estimates and inaccurate
      significance tests.

PMID- 8991319
TI  - Patients' view of the alliance of psychotherapy: exploratory factor analysis of
      three alliance measures.
AB  - Extending a previous study (R.L. Hatcher, A. Barends, J. Hansell, & M.J.
      Gutfreund, 1995), factor analysis of 3 alliance measures completed by 231
      patients explored patients' views of the alliance. Two of 6 factors, Confident
      Collaboration and Idealized Relationship (with the substantial general factor
      removed), correlated with patients' estimate of improvement (rs = .37 and -.23,
      respectively; p < .001). Patients view the core of the alliance as a purposive
      mutual collaboration, or working alliance; patients who acknowledge some
      hostility do better in therapy. Three other factors--Goals and Tasks, Bond, and
      Dedicated Patient--resemble established subscales but are unrelated to
      improvement beyond the general factor. Factor 6 assesses improvement rather than
      alliance. The collaborative working alliance should be given prominence in
      alliance theory and measurement.

PMID- 8991320
TI  - Meta-analytic evaluation of skills training research for individuals with severe
      mental illness.
AB  - A meta-analysis of 68 studies examined the effectiveness of skills training for
      individuals with severe mental illness and the influence of such factors as
      methodological rigor, choice of outcome measures, and service settings. The
      methodological quality of these studies was generally very good. Skills training
      was found to be moderately to strongly effective in increasing skill acquisition
      and reducing psychiatric symptoms. However, effect size varied by type of outcome
      measure, with situationally specific measures yielding larger effects than
      measures of skill usage and role functioning. Studies rarely examined whether
      acquired skills were used outside the training setting. Surprisingly, most
      studies were confined to inpatient settings, and most focused exclusively on
      social skills. Implications are discussed for future research.

PMID- 8991321
TI  - Narrative elaboration: test of a new procedure for interviewing children.
AB  - Because young children provide incomplete accounts of the past and tend to
      acquiesce to leading questions, procedures are needed to help them describe past
      events fully, without contaminating memory. This study tests the efficacy of
      "narrative elaboration," an innovative procedure designed to expand children's
      spontaneous reports of past events, reducing the need for leading questions. One
      hundred thirty-two children from 2 age groups (7-8 years and 10-11 years) were
      assigned randomly to 1 of 3 preparation conditions: (a) narrative elaboration
      intervention, (b) instruction-based intervention, and (c) control group. After
      participating in a staged activity and subsequent preparation sessions, children
      were interviewed about the activity. Children in the narrative elaboration
      condition demonstrated a 53% improvement in spontaneous recall over the control
      group, without compromising accuracy. Younger children using the narrative
      elaboration procedure performed at the level of older children in the control
      group. Discussion centers on implications for interviewing child witnesses and
      preparing them for courtroom examination.

PMID- 8991322
TI  - Process, life events, and symptomatic change in brief eclectic psychotherapy.
AB  - Brief eclectic psychotherapy was intensively studied using a time series approach
      to interrelate intrasessional processes, life events, and intermediate outcomes.
      The alliance demonstrated large global effects on outcome whereas therapist-rated
      high quality sessions preceded decreases in intersessional symptom levels
      (intermediate outcomes). Negative life events and negative intrasessional
      emotional experiences (rejection and dysphoria) anteceded increases in
      intersessional symptoms. Changes in subjective life events were associated with
      preceding intrasessional processes. It appeared that process might partially
      exercise its outcome effects by influencing patients' experience of their daily
      lives, which in turn, influenced intersessional symptom levels. Insight
      apparently occurred at the culmination of a 3-step process that was not directly
      related to symptom reduction. It was speculated that insight may function to
      consolidate therapeutic change. Relationships among other process measures were
      also described.

PMID- 8991323
TI  - Confirmatory P-technique analyses of therapist discourse: high-versus low-quality
      child therapy sessions.
AB  - From a sample of 35 child therapy sessions, 3 of the highest and 3 of the lowest
      quality sessions (HQS and LQS) were identified by independent ratings on the
      Loyola Child Psychotherapy Process Scales. Each of the 535 therapist-utterances
      in the HQS and the 372 therapist-utterances in the LQS were rated on 15 language
      interaction scales. Principal-components P-technique analyses were applied
      separately to the HQS and LQS, revealing 3 factors, Responsive Informing (RI),
      Initiatory Questioning (IQ), and Positive Regard (PR), that seemed to correspond
      across session types. Using confirmatory P-technique, a general measurement model
      with acceptable goodness-of-fit was determined for HQS. Two factors emerged: RI
      and IQ but not PR. Using a bootstrap procedure, random halves of the HQS were
      repeatedly sampled and compared via multigroup confirmatory factor analysis to
      create a reference distribution of the magnitudes of their difference chi
      squares. Random resamples of HQS and LQS were then compared, resulting in a
      second reference distribution. Statistical tests and effect-size measures
      revealed replicable and large differences between sessions types.

PMID- 8991324
TI  - Community-based resilient peer treatment of withdrawn maltreated preschool
      children.
AB  - The purpose of the present study was to evaluate differences in the social play
      of maltreated and nonmaltreated preschool children and the effectiveness of a
      resilient peer treatment (RPT) for socially withdrawn victims of physical abuse
      and neglect. RPT is a peer-mediated classroom intervention based on a
      developmental-ecological model. It involves pairing withdrawn children with
      resilient peers in the natural classroom under the supervision of a parent
      assistant. Forty-six Head Start children, of whom 22 were maltreated, were
      randomly assigned to RPT and control conditions. Outcome variables were
      observational categories of social play and standardized teacher ratings. Before
      treatment, maltreated children were significantly more isolated and less
      interactive in peer play than nonmaltreated children. RPT resulted in a
      significant increase in positive interactive peer play and a decrease in solitary
      play for maltreated and nonmaltreated, socially withdrawn children. Moreover,
      treatment gains in social interactions were validated 2 months following
      treatment. Findings are discussed in terms of a developmental-ecological model.

PMID- 8991325
TI  - Interpersonal contact and acceptance of persons with psychiatric disorders: a
      research synthesis.
AB  - This meta-analytic review predicted and confirmed that interpersonal contact
      between mental health employees or students and persons diagnosed with
      psychiatric disorders is associated with improved attitudes toward the latter
      group. As also predicted, the amount of attitude change was found to be smaller,
      although still significant, when the evaluative measure described a group of the
      "mentally ill" rather than specific individuals, and when the respondents were
      mental health employees rather than students. Contrary to predictions, contact
      interventions of longer duration were not associated with greater attitude
      changes. It is concluded that contact interventions occurring in mental health
      settings are effective in promoting attitude changes toward persons with
      psychiatric disorders, and methodological refinements that should strengthen the
      effectiveness of future contact interventions are outlined.

PMID- 8991326
TI  - Short-term memory and strategy use in children with insulin-dependent diabetes
      mellitus.
AB  - The present study was designed to examine recall and rehearsal in short-term
      memory among children with insulin-dependent diabetes mellitus (IDDM). Children
      with onset of IDDM before age 5 years, children with onset after 5 years, and
      children without IDDM were administered a measure of short-term memory that
      provides information about rehearsal as well as level of recall. Children with
      later onset of diabetes and children without IDDM were expected to recall more
      words and use more effective rehearsal strategies than children with early onset
      of diabetes. Results indicate that children diagnosed with IDDM early in life
      used similar rehearsal strategies but recalled fewer words than children with
      later onset of diabetes and children without IDDM. In addition, results provide
      evidence that children who are in poor control of their diabetes did not use
      strategies designed to increase recall as often, or as well as, children in
      better control of their diabetes.

PMID- 8991327
TI  - Is youth victimization related to trauma symptoms and depression after
      controlling for prior symptoms and family relationships? A longitudinal,
      prospective study.
AB  - The common finding linking symptoms such as posttraumatic stress disorder (PTSD)
      and depression with youth victimization (e.g., sexual abuse) might well be
      artifactual if preexisting psychopathology or disturbed family relationships
      create a common risk for both later victimization and later symptoms. This study
      used a longitudinal, prospective design to examine this issue. In a national
      random sample telephone survey, children 10 to 16 years old were interviewed and
      then reinterviewed approximately 15 months later about psychological problems,
      family relationships and victimization experiences that had occurred in the
      interim. Victimization in the interim was associated with PTSD-related symptoms
      and depression measured at Time 2, even after controlling for these symptoms and
      the quality of the parent-child relationship at Time 1. The association was
      particularly strong for sexual abuse, parental assault, and kidnapping
      experiences. However, these data also suggest that some of the apparent
      association found in cross-sectional studies between victimization and
      psychopathology may be due to prior psychopathology (but not parent-child
      relationship problems), which puts children at risk for both victimization and
      later symptoms.

PMID- 8991329
TI  - Assessing dissimulation among Social Security disability income claimants.
AB  - Social Security disability income programs have been tested by increasingly
      politicized concerns regarding widespread fraud among claimants. This study was
      an initial investigation of malingering among claimants in Los Angeles seeking
      disability income on psychological grounds. After a review of 100 disability
      income applications, a population-appropriate instrument was developed from
      established psychometric indices of malingering. The Composite Disability
      Malingering Index was completed by 167 disability claimants (possible
      malingerers), a sex, age and IQ cognate group of 63 psychologically disabled
      individuals without incentive to malinger (disabled nonmalingerers), and 45
      disability examiners with instructions to malinger (instructed malingerers). The
      mean score of instructed malingerers and the score at the 95th percentile of the
      disabled nonmalingerers converged, indicating 8 as the critical score. This
      cutting score found 32 (19%) of disability claimants to be malingering. Self
      reported substance abuse history was the only participant variable that
      significantly predicted higher malingering scores.

PMID- 8991328
TI  - Reasons for depression and the process and outcome of cognitive-behavioral
      psychotherapies.
AB  - This study examined the relationships between clients' reasons for depression and
      the process and outcome of a cognitive therapy (CT) and a behavioral activation
      (BA) treatment for major depression. Reason giving was conceptualized as the
      tendency to offer multiple explanations for a problem. Different reasons for
      depression were also thought to match or mismatch the theoretical model
      underlying each treatment. Reasons for depression were assessed pretreatment with
      a previously developed questionnaire. Process variables including homework
      compliance and perceived treatment helpfulness were measured early in treatment.
      Results demonstrated that perceived helpfulness of the treatment was associated
      with positive outcomes in BA. Reason giving was associated with worse outcomes in
      BA. Specific reasons also predicted differential outcome in the 2 treatments.
      Clients who endorsed existential reasons for depression had better outcomes in CT
      and worse outcomes in BA. Relationship-oriented reasons were consistently
      associated with negative process and outcome in CT. Results are discussed in
      terms of the function of reason giving and the role of specific explanations for
      depression in treatment process and outcome.

PMID- 8991330
TI  - Promoting healthier behaviors, attitudes, and beliefs toward sun exposure in
      parents of young children.
AB  - The present study examined the impact of a conceptually driven intervention
      designed to increase skin cancer knowledge and promote healthier, "sun-safe"
      attitudes, beliefs, and behaviors about sun exposure in mothers of children ages
      6 months to 10 years old. Participants (N = 55) were assigned to a comprehensive
      prevention program (CPP), information-only condition (IOC), or a no-information
      control group (NIC). An assessment battery measuring skin cancer knowledge, sun
      safe behaviors, and sun exposure attitudes and beliefs was administered at
      baseline, 2 weeks postintervention, and 12 weeks postintervention. Consistent
      with prediction, mothers in the CPP and IOC groups showed significant increases
      in skin cancer knowledge; however, only those in the CPP condition showed
      increases in sun-safe behaviors, attitudes, and beliefs that were maintained at
      the 12-week follow-up. Also, results provide support for the influence of
      perceived severity, self-efficacy, response-efficacy, and perceived barriers on
      sun-safe behaviors.

PMID- 8991331
TI  - Sociocultural and legal implications of creating and sustaining life through
      biomedical technology.

PMID- 8991332
TI  - HIV and AIDS in Africa. African policies in response to AIDS in relation to
      various national legal traditions.

PMID- 8991333
TI  - Modern reproductive technologies. Legal issues concerning cryopreservation and
      posthumous conception.

PMID- 8991334
TI  - Emotional support in pediatric trauma: remembering children like Caleb.
AB  - Sudden traumatic injury can be devastating to a child and family, especially when
      a loved one dies. Through a young boy's letter, health care providers can see how
      children try to cope with traumatic injury and death. Suggestions regarding ways
      to promote healing of the child's emotional wounds are also included.

PMID- 8991335
TI  - Effects of social support, stress, and level of illness on caregiving of children
      with AIDS.
AB  - The purpose of this descriptive correlational study was to explore the
      relationship between social support, stressors, level of illness, and perceived
      caregiver burden in caregivers of children with HIV/AIDS. Instruments used were:
      (1) the Classification System for Human Immunodeficiency Virus (HIV) Infection in
      Children Under 13 Years of Age (1987), (2) the Daily Hassles Scale, (3) the
      Tilden Interpersonal Relationship Inventory (IPRI), (4) the Derogatis Stress
      Profile (DSP), and (5) the Caregiver Appraisal Scale. The sample was drawn from
      two medical centers in New Jersey. The 49 caregivers of children with perinatally
      acquired HIV were predominantly HIV-positive biological mothers of African
      American descent whose education ranged from 8th grade through college. One-half
      of the children were classified at the CDC P2 level. Descriptive statistics and
      stepwise multiple regression were used to analyze the data. The results of the
      DSP indicated subjects were slightly below the 70th percentile for anxiety,
      depression, hostility, and work stressors and that subjects' social support
      levels were in the upper end of the low support category. Stepwise regression
      indicated that depression and anxiety predicted 40% of the variance in caregiver
      burden (R2 = .399; F = 14,985; p = .000). Hostility and level of social support
      predicted 37% of the variance in caregiving impact (R2 = .37; F = 13.254; p =
      .000). Finally, social support predicted 17.5% of the variability in the
      caregivers' sense of caregiving competency (R2 = .175; F = 9.788; p = .003). The
      child's level of illness and HIV status of caregiver did not significantly
      predict variance in caregiving appraisal.

PMID- 8991336
TI  - Therapeutic play and bone marrow transplantation.
AB  - Constructive, therapeutic play is an essential part of the care of children with
      long-term hospitalizations. The O'Connor theoretical framework supports the
      importance of play in ensuring the emotional, developmental, and physical health
      of children. The negative effects of long-term hospitalization are particularly
      evident for children who have undergone bone marrow transplants and must be kept
      in germ-free environment and isolation for extended periods of time. This article
      describes a successful play therapy program in a Bone Marrow Transplant Unit,
      using a play cabinet designed to provide readily available, sterilized toys that
      are appropriate for each of four age groups. Two cases are presented that show
      the efficacy of the use of the play cabinet in play therapy programs.

PMID- 8991337
TI  - Reliability and validity of the Faces and Word Descriptor Scales to measure
      procedural pain.
AB  - Reliability and validity of the Faces and Word Descriptor Scales to measure pain
      in verbal children undergoing painful procedures were assessed. Test-retest
      reliability and construct and discriminant validity were supported for both
      instruments among a sample of 118 children in three age groups (3-7, 8-12, 13
      18). Construct validity was determined by comparisons with a visual analogue
      scale and a numerical scale with known validity. A majority of the children
      preferred to use the Faces scale when providing self-report of pain regardless of
      age. The Faces and Word Descriptor Scales are valid and reliable instruments to
      measure procedural pain intensity.

PMID- 8991338
TI  - Postoperative use of pediatric pain scales: children's self-report versus nurse
      assessment of pain intensity and affect.
AB  - The purpose was to examine nurses' use of pediatric pain scales and to compare
      their estimate of the child's pain intensity and affect with the child's self
      report. The Analog Chromatic Continuous Scale (ACCS) was used for pain intensity
      and the McGrath Affective Faces Scale (MAFS) for pain affect. Self-report of pain
      was obtained from 124 hospitalized postoperative children aged 5 to 17 years and
      compared with estimates of 44 pediatric nurses randomly assigned to either an
      experimental or control group. Experimental nurses used the ACCS and MAFS to
      obtain pain ratings whereas control nurses made estimates according to their
      customary method of assessment. Findings revealed that only 36% of the nurses had
      at any time used a pediatric pain scale. Correlations between the experimental
      nurses' ratings and the child's self-report were significantly higher than the
      control nurses' estimates and the child's self-report. The correlation between
      the child's self-report of pain intensity on the ACCS and of affect on the MAFS
      was r = .612, suggesting that nurses' use of both an intensity and affect
      pediatric pain scale would more accurately reflect the child's pain experience.

PMID- 8991339
TI  - Behavioral responses of healthy Chinese siblings to the stress of childhood
      cancer in the family: a longitudinal study.
AB  - Advances in the treatment of childhood malignancies have dramatically altered
      survival rates of children with cancer, changing the nature and scope of
      stressors that their families encounter. Very little is known about how childhood
      cancer affects healthy Chinese siblings and what can be done to help children
      adjust to this stressful life event. The cognitive theory of psychological stress
      was the framework for this study. The purpose of this research was to explore
      behavioral responses of healthy Chinese siblings in Taiwan to childhood cancer in
      the family and to examine the factors that may contribute to the presence or
      absence of behavioral problems in these siblings, using a 12-month longitudinal
      data set. Forty-five Chinese families were selected through referrals and a
      cancer foundation name roster. Content analysis of qualitative and quantitative
      sibling data revealed major stressor themes of inadequate knowledge, reduced
      family communication, and insufficient support. Healthy Chinese siblings showed
      significantly more behavior problems and fewer social competence behaviors than a
      standardized normal western population.

PMID- 8991340
TI  - Maternity length of stay and public policy: issues and implications.

PMID- 8991341
TI  - Health fair for the homeless.

PMID- 8991342
TI  - The growth of children for two generations at an Australian aboriginal community.

PMID- 8991343
TI  - Who are "Milliman & Robertson" and how did they get in my face?

PMID- 8991344
TI  - ECG intervals in acute bipolar and schizophrenic relapse.
AB  - Psychosis in general and acute relapse of bipolar illness, in particular, are
      associated with elevated catecholamine excretion, cardiovascular changes, and
      changes in intracellular calcium concentration. In an effort to determine if
      these changes result in observable ECG abnormalities, we retrospectively examined
      ECG parameters of acutely disturbed bipolar and schizophrenic patients. There
      were no discrete patterns of abnormalities, and no significant differences were
      observed between the two patient groups. Most ECG changes in acutely hospitalized
      bipolar and schizophrenic patients appear to be benign.

PMID- 8991345
TI  - Role of cytokines in parasitic disease.

PMID- 8991346
TI  - Typhoid perforation treated with and without metronidazole along with
      chloramphenicol, gentamycin.
AB  - Forty cases of typhoid ileal perforation were treated surgically in three years.
      Chloramphenicol and gentamycin were given to 20 patients, while the remaining 20,
      received Metronidazole additionally. The mortality rate was 60 percent in the
      first and 40 percent in the second group.

PMID- 8991347
TI  - Changing spectrum of typhoid.
AB  - To determine the changing spectrum of typhoid fever, a study was conducted on 240
      cases of typhoid fever, admitted over a period of 4 years. The classical
      'Stepladder fever' and 'relative bradycardia' were less commonly seen.
      Presentation as hepatitis, psychosis, meningism, myocarditis, polyneuropathy and
      diarrhea were encountered in a small number of patients. Reversible proximal
      myopathy occurred in four patients and all of them recovered completely over a
      period of 2-3 weeks. The total leukocyte counts were within normal range in most
      of the cases. Bone marrow cultures were positive in all untreated and partially
      treated patients. All strains of Salmonella typhi in this study were sensitive to
      ofloxacin ceftriaxone and ciprofloxacin.

PMID- 8991348
TI  - Evaluation of paromomycin sulphate topical ointment as effective therapeutic
      agent in cutaneous leishmaniasis.
AB  - This is a prospective open study of randomly selected 35 patients with a single
      sore of cutaneous leishmaniasis who were treated with paromomycin sulphate
      topical ointment for 4 weeks. According to the observations made on days 0, 15,
      45 and 105 after the careful application twice a day in 2 lengths from one side
      of the lesion to the other at right angles to each other and then smeared to
      cover the whole surface of the sore, the overall efficacy of the ointment as
      therapeutic agent was 91%. There was a mild and temporary adverse reaction in the
      form of painless, non-itching nodulation around the ulcers in 10 (28%) patients
      after 15 days application which disappeared within 5-7 days of further
      application. It thus proved a promising, simple and inexpensive remedial agent
      without any undesirable side effects as compared to other complicated and
      unpredictable therapeutic regimens.

PMID- 8991349
TI  - Seroprevalence of antibodies to Toxoplasma gondii, with particular reference to
      obstetric history of patients in Rawalpindi-Islamabad, Pakistan.
AB  - Six hundred and forty blood samples were obtained from Rawalpindi-Islamabad to
      determine the frequency of Toxoplasma gondii antibodies using indirect
      immunofluorescent antibody (IFA) test. Two hundred and forty samples were from
      suspected cases of Toxoplasmosis. Forty (17%) cases were positive for IgG
      antibody. Seven (3%) of these cases showed antibody titre greater than 1:320. Of
      65 children tested, 8 (12.30%) were positive. Four (6%) children had a rising
      titre from 1:160 to 1:1025. Prevalence of Toxoplasma antibodies was correlated to
      mode of living, maternal obstetric history, their animal contact and age of the
      children.

PMID- 8991350
TI  - Predictors of mortality in hemodialysis.
AB  - One hundred and five patients enrolled in the maintenance haemodialysis programme
      at The Kidney Centre were studied retrospectively to identify patient
      characteristics associated with increased mortality. Hypertension (relative risk
      10.03, P < 0.001), serum albumin < 3 G/dl (relative risk 2.60, p < 0.05),
      diabetes mellitus as a cause of End Stage renal disease (relative risk 2.54, p <
      0.001), age > 55 years (relative risk 1.8, p) were associated with higher risk of
      mortality, while sex had no statistically significant effect.

PMID- 8991351
TI  - The extranasal glioma--a cause of neonatal respiratory distress.

PMID- 8991352
TI  - Lumbar discitis complicating percutaneous laser disc decomposition: case report
      and review of literature.

PMID- 8991353
TI  - Animal models in biomedical research.

PMID- 8991354
TI  - Genetic markers.

PMID- 8991355
TI  - Suicidal symptoms in depressed Pakistani patients.
AB  - Depressive patients are at a high risk for suicide. The data on the frequency of
      suicidal symptoms in depressed patients, however, varies widely. This paper
      describes the extent of these symptoms in a group of Pakistani patients. Contrary
      to the findings of other Muslim countries, forty five percent of our patients
      showed suicidal psychopathology. Female patients showed more suicidal ideation
      and significant association was found between severity and duration of depressive
      illness with these symptoms. These findings are also discussed in terms of their
      importance in early recognition of these symptoms.

PMID- 8991356
TI  - Biochemical changes during a cross-over treatment of doxazosin, moduretic and
      amlodipine in hypertensive patients.
AB  - A cross-over study was done to compare the effects of doxazosin, moduretic and
      amlodipine on biochemical values in 9 hypertensive Nigerians aged 35 to 65 years.
      Doxazosin therapy was characterized by significant increase in the levels of mean
      plasma total protein and albumin, while moduretic therapy showed significant
      reduction in the mean values of plasma creatinine and calcium. All other
      parameters did not show any significant variation during doxazosin and moduretic
      treatment phases; and amlodipine therapy did not have any effect on the
      biochemical values of the hypertensive patients.

PMID- 8991357
TI  - Single plane fluoroscopic guided biopsy of thoracic lesions.
AB  - Single plane fluoroscopic guided biopsy was performed successfully in 61 of 70
      patients with thoracic lesions using inexpensive spinal needles. Lesions smaller
      than 2 cm and those located within 2 cm distance from vascular structures were
      not biopsied using this technique. Post-biopsy pneumothorax developed in 15 of
      the 46 biopsies of the intrapulmonary lesions. Five patients required a chest
      tube placement for symptomatic pneumothoraces. There were no fatalities. It is
      suggested that in a selected group of patients single plane fluoroscopic guided
      biopsy is a safe and fast method for diagnosis of a thoracic lesion.

PMID- 8991358
TI  - Plasma beta-carotene concentrations in pregnancies, newborn infants and their
      mothers.
AB  - Concentrations of beta-carotene were determined in maternal and fetal blood. The
      samples were collected from 33 mothers, their 33 newborns and 50 pregnant and 29
      non-pregnant women. Beta-carotene concentrations of the non-pregnant, pregnant,
      newborn infant and their mothers were 140.31, 171.54, 63.57 and 175.74
      micrograms/dl, respectively. There was a significant correlation (P < 0.001)
      between beta-carotene values of the maternal plasma and cord plasma. Mean
      maternal plasma beta-carotene concentration was higher (P < 0.0005) than that of
      the cord. These results suggest that plasma transport capacity of beta-carotene
      was low from mother to their fetus.

PMID- 8991359
TI  - Critical appraisal by reading for medical students--a case study from Pakistan.
AB  - Doctors read literature to keep abreast of medical advances. A recommendation
      from the 1993 World Summit for Medical Education is that medical schools should
      teach medical students to critically appraise scientific reports. The Department
      of Community Health Sciences of Aga Khan University Medical College teaches basic
      research methods to medical students. This is now supplemented with "Critical
      Reading". Critical reading was first taught to 67 third year students between
      October, 1993 and May, 1994. A "validity check-list for critical readers" was
      introduced in a two week orientation consisting of three one-hour classroom
      sessions and four one-hour small group sessions. Thereafter, small groups met
      monthly to critique clinical epidemiological reports relevant to current organ
      system teaching. The students reading attitudes and critical appraisal skills
      were assessed through continuous assessment and a written final examination with
      questionnaire. All but three students passed the final examination (mean score
      (74%, standard deviation 12%). Sixty-four of 67 (96%) completed questionnaires.
      All (73% strongly) agreed that critical reading skills were essential, but only
      30% strongly agreed that they had, indeed, mastered the skills. Ninety-seven
      percent (56% strongly) disagreed that year three was too early to start critical
      reading. Clinical teaching staff expressed interest in learning these skills.
      Students benefited from and enjoyed this first critical reading course. It
      strengthened ties between clinical and community health sciences teaching staff.
      The critical reading skills of the clinical teaching staff is being addressed in
      seminars to strengthen institutional research capacity.

PMID- 8991360
TI  - Frequency of metabolic bone disease in haemodialysis patients.
AB  - The frequency of metabolic bone disease related to secondary hyperparathyroidism
      was studied in 47 haemodialysis patients, using biochemical, radiological
      parameters and bone biopsy (30 males, 17 females; mean age 48 years). The
      duration on dialysis ranged from 1-5 years. Hypocalcemia was found in 47% while
      62% had raised phosphorus levels and 49% raised alkaline phosphatase. Serum
      parathyroid hormone was elevated in 86%, while in 13% it was markedly raised. On
      radiological examination there was generalized osteopenia in 49% and decreased
      bone density in 21%. In 30% no radiological abnormality was detected. In 40% bone
      biopsy revealed osteomalacia, mixed osteodystrophy 21%, osteoporosis 8.5% and in
      25% no histological abnormality was observed.

PMID- 8991361
TI  - Endobronchial tuberculosis--manifesting by coughing up of bronchial cartilage.

PMID- 8991362
TI  - Human parvovirus B19 associated non-immune hydrops fetalis.

PMID- 8991364
TI  - Prevalence of hepatitis B infection in beta thalassaemia major patients.

PMID- 8991363
TI  - The role of drugs in high altitude disorders.

PMID- 8991365
TI  - Scope of ethnopsychiatry in Pakistan.

PMID- 8991366
TI  - Risk of uterine rupture after the partographic 'alert' line is crossed--an
      additional dimension in the quest towards safe motherhood in labour following
      caesarean section.
AB  - To determine if prolonged active phase of labour is associated with increased
      risk of uterine scar rupture in labour following previous lower segment caesarean
      section, a retrospective cohort study (1988-91) was done to analyse active phase
      partographs of 236 patients undergoing trial of labour following caesarean
      section, 7 (3%) of whom had scar rupture. After onset of active phase (3 cm
      cervical dilatation), a 1 cm/h line was used to indicate "alert". A zonal
      partogram was developed by dividing the active phase partographs into 5 time
      zones: A (area to the left of "alert" line), B (0-1 h after "alert" line), C (1-2
      h after "alert" line), D (2-3 h after "alert" line) and EF (> 3 h after "alert"
      line). The relative risk of uterine scar rupture was calculated for different
      partographic time zones. The relative risk of uterine scar rupture was 10.5 (95%
      confidence interval 1.3-85.5, p = 0.01) at 1 hour after crossing the "alert"
      line; 8.0 (95% confidence interval 1.6-40.3, p = 0.009) at 2 hours after crossing
      the "alert" line; and 7.0 (95% confidence interval 1.6-29, p = 0.02) at 3 hours
      after crossing the "alert" line. In women undergoing trial of labour following
      caesarean section, prolonged active phase of labour is associated with increased
      risk of uterine rupture. A zonal partogram may be helpful in assessing this risk
      in actively labouring women who cross the partographic "alert" line.

PMID- 8991367
TI  - Stress hormones and acid-base status in human fetuses at term delivery: the
      effect of delivery method.
AB  - To evaluate the effect of delivery mode on fetal stress hormones and acid-base
      status and also to investigate the relationship between fetal acidemia and these
      hormones. 64 women with term pregnancies were studied. All had singleton, healthy
      pregnancies. Twenty one women were delivered by spontaneous vaginal route, 23 by
      vaginal route following oxytocin infusion and 20 by elective caesarean section.
      Umbilical cord blood samples were obtained immediately following the delivery.
      Blood gas (pH, pCO2, pO2) and hormonal analysis (Cortisol, dehydroepiandrosterone
      sulphate, prolactin, androstenedione) were done in arterial and venous cord blood
      samples respectively. Higher pO2 and prolactin, lower pH levels were found in
      caesarean section compared to other two groups (p < 0.05). At the time of
      delivery 11 infants had acidemia (pH < 7.20) as judged by pH of umbilical
      arterial blood. Acidemic group had higher cortisol and pCO2; lower pH and pO2
      levels compared to non-acidemic group (p < 0.05). Method of delivery may affect
      acid-base and hormonal status of human fetus. Fetal acidemia may alter fetal
      adrenal steroidogenesis leading to increased fetal cortisol production.

PMID- 8991368
TI  - Method of obtaining and preparation of fresh human amniotic membrane for clinical
      use.
AB  - Amniotic membrane was obtained from 36 mothers seronegative for hepatitis B
      surface antigen and syphilis, undergoing caesarean section. Membrane was
      separated from placenta and was washed first with saline and then saline solution
      containing penicillin. The processed membrane was found to be sterile and useable
      for up to one week. Of 36 placentas obtained, 33 were utilized in 22 patients,
      with no history of penicillin allergy, as biological dressing in acute burns.
      Each patient received three applications of membrane one every other day, over a
      period of six days. This method of obtaining amniotic membrane was simple and
      more practical for maintaining the biological effectiveness of membrane, as shown
      by quantitative reduction of bacterial counts in burn wounds.

PMID- 8991369
TI  - Changes in plasma electrolytes during acclimatization at high altitude.
AB  - The effects on plasma electrolytes and related hormones were determined in non
      acclimatized low lander males, exposed for 96 hours to an altitude of 4424
      meters. Twenty healthy soldiers aged 18-34 years travelled by road from an
      altitude of 2303 meters to 4424 meters over a period of 10 hours. Plasma sodium
      levels (142.09 +/- 1.14 mmol/1) and aldosterone (16.61 +/- 5.70 ng/ml) decreased
      to 139.69 mmol/1 and 11.6 +/- 4.60 ug/ml respectively after 96 hours of acute
      exposure to high altitude (p < 0.05). The plasma potassium and chloride levels
      did not show significant change, while, plasma HCO3 decreased gradually from
      21.06 +/- 1.38 mmol/1 to 18.55 +/- 0.82 mmol/1 after 96 hours exposure to this
      altitude (p < 0.01). The plasma ionized calcium and plasma phosphate
      concentration decreased from 1.32 +/- 0.11 mmol/1 and 1.58 +/- 1.3 mmol/1 to 1.20
      +/- 0.05 mmol/1 and 1.47 +/- 0.99 mmol/1 respectively (p < 0.05). Plasma
      parathyroid hormone (PTH) level increased from 4.54 +/- 2.1 ng/ml to 11.19 +/-
      4.31 ng/ml after 48 hours with subsequent decline to 2.52 +/- 1.7 ng/ml after 96
      hours exposure to high altitude. It may be concluded that the process of
      acclimatization to sudden exposure to high altitude is characterised by fall in
      plasma aldosterone and PTH with subsequent decrease of related electrolytes.

PMID- 8991370
TI  - Harassment in medical profession--myth or reality in Pakistan.

PMID- 8991371
TI  - Penile fracture.

PMID- 8991372
TI  - The adjuvant effect of oxytocin on GnRH analogue buserelin.

PMID- 8991373
TI  - Vesicovaginal fistula--more than an obstetric problem.

PMID- 8991374
TI  - Cachectin/tumor necrosis factor.

PMID- 8991375
TI  - Two hundred years on: Jenner and the discovery of vaccination.

PMID- 8991376
TI  - Double knockout highlights value of endothelial selectins.

PMID- 8991377
TI  - N-terminal processing: two-faced chemokines?

PMID- 8991378
TI  - Obeying V(D)J rules in vitro.

PMID- 8991379
TI  - B cells and their fate in health and disease.
AB  - A recent meeting discussed advances in our understanding of germinal centers, B
      cell malignancies and B-cell signal transduction. Such developments have yielded
      a more refined view of the role of B-cells in health and disease.

PMID- 8991380
TI  - Integrins as promiscuous signal transduction devices.
AB  - Recent studies suggest physical and functional interactions of
      glycosylphosphatidylinositol (GPI)-linked proteins (CD14, CD16b and CD87) with
      leukocyte beta 2 integrins. As discussed in this article, it now appears that
      beta 2 integrins relay proinflammatory information from GPI-anchored membrane
      receptors to the cytoplasm via exodomain interactions.

PMID- 8991381
TI  - NK-cell receptors and recognition of MHC class I molecules.
AB  - Two families of natural killer (NK)-cell receptors exist that interact with major
      histocompatibility complex (MHC) molecules, thereby preventing cytotoxic cells
      from killing target cells. The expanding knowledge of these receptors provided
      the focus for a recent meeting.

PMID- 8991382
TI  - IL-12: a key cytokine in immune regulation.
AB  - It is now apparent that interleukin 12 (IL-12) is of central significance in the
      regulation of immune responses. At a recent meeting, immunologists from
      preclinical and clinical backgrounds gathered to discuss basic concepts in IL-12
      biology, and the potential of IL-12 as a target for immunointervention.

PMID- 8991383
TI  - Controlling HIV pathogenesis: the role of the noncytotoxic anti-HIV response of
      CD8+ T cells.
AB  - Noncytotoxic CD8+ T cells may play a critical role in preventing progression to
      disease following human immunodeficiency virus (HIV) infection. This antiviral
      response, mediated by a novel CD8+ T-cell antiviral factor (CAF), occurs soon
      after infection and is maintained in asymptomatic individuals. Here, Jay Levy and
      colleagues propose that this antiviral activity represents a natural cellular
      immune reaction that controls HIV production and protects the host from potential
      harmful effects of cytotoxic T lymphocytes.

PMID- 8991384
TI  - IL-4-induced immune deviation as antigen-specific therapy for inflammatory
      autoimmune disease.
AB  - Organ-specific autoimmune diseases are mediated by interferon gamma (IFN-gamma)
      producing T helper 1 (Th1) cells. Here, Martin Rocken and colleagues review the
      experimental basis for an antigen-specific therapeutic approach to inflammatory
      autoimmune diseases. This strategy involves selective deviation of harmful Th1
      responses towards an anti-inflammatory, interleukin 4 (IL-4)-producing Th2
      phenotype.

PMID- 8991385
TI  - The nature of autoantigens targeted in autoimmune endocrine diseases.
AB  - Autoimmune endocrine diseases result from autoimmune processes involving
      autoreactive T cells and/or autoantibodies. Considerable progress has been made
      in elucidating the self- (auto-) antigens involved in these processes. These
      include tissue-specific membrane receptors, enzymes and secreted hormones. As
      discussed here by Yao-Hua Song and colleagues, diagnostic and therapeutic
      applications should now result from these discoveries.

PMID- 8991386
TI  - Antibody neutralization of HIV-1.
AB  - Neutralizing antibodies are a major component of host defense against viruses,
      and appear to be particularly important in limiting the spread of cell-free
      virus. Results from vaccine trials in animal models suggest that these antibodies
      may contribute to protection against human immunodeficiency virus (HIV)
      infection. Here, Pascal Poignard and colleagues discuss recent developments in
      this area, with particular emphasis on the measurement, specificity and mechanism
      of the antibody response, and its significance for vaccine production.

PMID- 8991387
TI  - [Learning and memory skills in patients with cryptogenic epilepsy].
AB  - The purpose of this investigation was to determine the nature of memory deficits
      in patients with cryptogenic epilepsy and partial seizures. Sixty-two patients
      were compared to forty-four controls on several verbal and visual memory tests
      (short-term memory, learning, long-term recall, and recognition). Performance in
      the patients group was significantly impaired only on the test of verbal delayed
      recall.

PMID- 8991388
TI  - [Critical illness polyneuropathy].
AB  - Critical illness polyneuropathy (CIP) is a recently identified entity for which
      reliable data is unavailable and of which the prevalence is unknown. Although the
      percentage of patients suffering CIP is low, more cases, including subclinical
      ones, are likely to be detected through the use of electroneurography. Any aged
      patient may be affected by CIP. It usually occurs a long stay in the intensive
      care unit (ICU) and is generally associated with sepsis, severe trauma and so
      called multiple organ failure. The main clinical sign is distal weakness in the
      lower extremeties, although finding one or more of the following signs is not
      uncommon: quadriparesis, quadriplegia, difficult weaning, loss of osteo-tendon
      reflexes and muscle atrophy. The pathophysiology of CIP is unknown, although such
      mechanisms as cell dehydration, increased proteolysis and the activation of
      certain cytokins have been suggested. Before diagnosing CIP, other neuromuscle
      diseases and several recently described toxic myopathies must be ruled out.
      Electroneuromyographic study of axonal lesions may be of great utility, whereas
      analyses have low specificity. Histologic examination, when possible, allows
      axonal lesions (but never demyelinization) to be observed along with the non
      specific changes of myopathy. Although no specific treatment is available, the
      long-term prognosis is good if the underlying disease that gave rise to ICU
      admission is controlled, and if rehabilitation therapy is started early.

PMID- 8991389
TI  - [The diagnosis and treatment of carpal tunnel syndrome].
AB  - Carpal tunnel syndrome (CTS) is a relatively benign condition whose incidence in
      the general population is about 10%. The clinical interest of CTS lies in the
      differential diagnosis of the syndrome relative to other conditions that may have
      a greater impact on the patient's overall health. The scientific interest lies in
      deciphering the pathophysiological mechanisms of proximal limb manifestations of
      patients with CTS, defining the cause of the lesion, and establishing the
      relationship between symptoms and electrophysiological findings. Electrodiagnosis
      is fundamental for CTS diagnosis, follow-up and research. Nevertheless, no
      universally accepted methodological criteria are available. Therapeutic advice at
      present is based more on clinical impression than on objective, reasoned
      evaluation. Serial clinical and electrophysiological studies are needed to
      evaluate treatment efficacy, functional regeneration, and clinico
      electrophysiological correlation.

PMID- 8991390
TI  - [Repeated strokes as a sign of multiple cerebral hydatid cysts].
AB  - A female patient with primary multiple cerebral hydatid cysts is described.
      Initial deterioration was followed several months later by reversible episodes of
      right hemiparesis, aphasia and sphincteral incontinence. This clinical picture
      has not been described in the literature and the etiopathogenic mechanism is
      uncertain.

PMID- 8991391
TI  - [Cystic meningioma of the optic chiasm].

PMID- 8991392
TI  - [Cerebrovascular intensive care units].

PMID- 8991393
TI  - [Renovascular arterial hypertension. Importance of subtraction digital
      angiography in its diagnosis].
AB  - The authors describe the material and the use method of intravenous digital
      subtraction angiography (IVDSA) before presenting the obtained results. The
      morphologic abnormalities of the renal arteries evidenced in 105 patients, are
      distributed by different pathologies such as: atherosclerosis 48 patients;
      fibromuscular dysplasia 27 patients; Takayasu's aortoarteritis 8 patients (7.6%);
      renal artery aneurysms 5 patients (4.8%); renal arterial emboli 1 patient (0.9%);
      iatrogenic 6 patients (5.7%); small kidney/hypoplastic renal artery 10 patients
      (9.5%). The authors draw also attention to an anatomic variant-the early
      bifurcation of the renal artery that should be evaluated under the
      pathophysiologic point of view. From this experience some conclusions emerge. The
      IVDSA permits the ambulatory screening of the renal arteries abnormalities with
      additive value in the cost/benefit ratio, that is translated in the increasing
      number of hypertensive patients who are identified as having renal artery
      abnormalities. The pathologies more frequently identified are the atherosclerotic
      in the old male and the fibromuscular dysplasia in the young female. The
      pathophysiologic significance of the early bifurcation of the renal artery needs
      further elucidation. According to the authors experience, the IVDSA has a
      paramount position and can even be the first test to be performed in the workup
      diagnostic approach to the hypertensive patient with moderate and strong
      suspection of RVH.

PMID- 8991394
TI  - [Acute cerebrovascular disorder and arterial hypertension. Prospective study with
      248 patients].
AB  - OBJECTIVE: To evaluate the hypertension associated to different types and sub
      types of cerebrovascular disease (stroke), with particular reference to the
      frequency of hypertension, the values of blood pressure, the risk factors and the
      involvement of other target organs. DEFINITION: Prospective study in 248 patients
      with acute stroke admitted to a Clinical Medicine Unit in three independent time
      periods. SETTING: Internal Medicine Clinic of University Hospital in Lisbon.
      METHODS: Medical, neurological and cardiologic examination were performed and all
      patients were also submitted to different complementary tests, including a
      computer tomography scan of the brain, and an echocardiogram. The values of blood
      pressure were measured in the admission at the urgent service and 24 h after in
      the the ward. We identified three sub-types of stroke: intracerebral hemorrhage
      (IH), ischaemic stroke (IS) and lacunes (L). For each sub-type and for those with
      hypertension or not, we evaluated: age, sex, duration of stay in hospital and
      mortality. We also compared for each sub-type the values of blood pressure, the
      risk factor and the repercussion on other target organs. PATIENTS: Two hundred
      and forty eight patients (52% were men) with mean age 68.0 +/- 10.2 years, and
      ages among 40 and 92 years. Thirty-seven patients (15%) died. MAIN RESULTS: In
      the entire population (n = 248) hypertension were more prevalent in IH 83% and L
      82% than in IS 59% (p < 0.0005). Hypertension was present in 172 patients (69%)
      and 81 (47%) were IS, 58 (34%) L and 33 (19%) IH. Sixty six percent of the 172
      patients with hypertension had at least another risk factor and the most aged
      ones (> 65 years old) were more frequent in IS 75% than in HI 45% or L 58% (p <
      0.001). For all subtypes blood pressure measurements were higher in admission
      than in ward and they were also higher in IH than in IS (p < 0.05). Hypertensive
      cardiopathy was more prevalent in IH 76% and L 61% than in IS 49% (p < 0.05).
      Renal failure was more frequent in IS 37% than in IH 28% and L 17% (p < 0.05).
      CONCLUSIONS: Hypertension is very frequent, and like advanced age is a major risk
      factor of stroke. Hypertension is frequently associated with one or more risk
      factors. Hypertensive cardiopathy is more related with IH and L and the renal
      involvement with IS.

PMID- 8991395
TI  - [Assessment of cardiovascular reflexes in patients with mitral valve prolapse
      syndrome].
AB  - OBJECTIVE: Functional evaluation of Autonomic Nervous System in patients with
      Mitral Valve Prolapse Syndrome. DESIGN: Study of cardiovascular reflexes.
      SETTING: Out patients studied in the Laboratory for Study of Autonomic Nervous
      System Function of Santa Maria Hospital, Lisbon, Portugal. MATERIAL AND METHODS:
      We studied 20 patients with clinical and echocardiographic diagnosis of mitral
      valve prolapse, who presented Mitral Valve Prolapse Syndrome, without significant
      mitral regurgitation, and with normal left ventricular function. Cardiovascular
      reflexes were analysed by mean of five tests. RESULTS: In 75% of the cases,
      patients had results according to vagal hypofunction. Orthostatic hypotension was
      present in 40%. Among patients with orthostatic hypotension, 75% had postural
      phenomena. Among patients with postural phenomena, 75% had orthostatic
      hypotension. CONCLUSIONS: In the present study, patients behaviour hasn't been
      uniform. Vagal hypofunction was present in 75% and orthostatic hypotension in 40%
      of the cases. A relation has been found between orthostatic hypotension and
      postural into.

PMID- 8991396
TI  - [Cleft sternum in an infant].
AB  - The authors report the clinical case of a female black infant, one month 22 days
      old, with sternal malformation (complete sternal cleft). She didn't show other
      associated malformations. Early surgical repair was done with success. The
      relevant nomenclature of sternal defects is discussed.

PMID- 8991397
TI  - [Anatomic orientation in paranasal endoscopic surgery].
AB  - A major concern during endoscopic surgery of the paranasal sinuses are anatomic
      references, which aid in orientation and help to prevent complications. A step-by
      step description is made of anatomical landmarks and how they should be
      interpreted during surgery. New landmarks are described, as well as typical
      difficult situations and their solution. Acoustic and tactile references
      supporting endoscopic orientationare described for the first time.

PMID- 8991398
TI  - [The relation between human papilloma virus and cellular DNA content in
      epidermoid carcinoma of the head and neck].
AB  - The relation between the presence of gene sequences of human papilloma virus
      (HPV) and the development of abnormalities in cellular DNA content was analyzed
      in 31 squamous-cell carcinomas of the head and neck. The integration of HPV types
      16 and 6b by PCR and DNA content was studied by flow cytometry in 31 specimens
      from patients with squamous-cell carcinoma of the head and neck. Eighteen (58%)
      cases were aneuploid. HPV DNA was present in seven tumors (22.5%), five of then
      HPV-6b and two of them HPV-16. Aneuploidy correlated with poorly differentiated
      tumors. No correlation was found between HPV integration and either cellular DNA
      content or the degree of histological tumor differentiation. Therefore, the
      presence of HPV gene sequences did not seem to be associated with a higher
      incidence of aneuploidy in squamous-cell carcinoma of the head and neck.

PMID- 8991399
TI  - [The evolution of otitis media with effusion treated by transtympanic drainage].
AB  - One hundred sixty children with effusive otitis media who did not improve with
      medical treatment were reviewed. The evolution and complications observed in 294
      ears treated by myringotomy and ventilation tubes (grommets) over a three-year
      period were analyzed. Otorrhea occurred during grommet placement in 11.6%. The
      disease remitted in 84%. Recurrences occurred in 15.3%: 4.8% had different
      degrees of tympanic atelectasia and 0.7% had perforation. Three per cent of the
      children were reoperated for bilateral recurrence of otitis. Younger children and
      those whose had delayed surgery had a worse outcome. Insertion of ear grommets
      improved hearing.

PMID- 8991400
TI  - [Errors in computerized electronystagmography].
AB  - Computerized electronystagmography (ENG) is the analysis of the eye movement
      recordings using a computer program to identify nystagmus and quantitate response
      parameters. The results of 100 consecutive bithermal caloric tests of patients
      complaining of peripheral vertigo were analyzed by computer. All computer
      analyses were reviewed by authors and either were deemed accurate as made by the
      computer or were corrected manually. Final test interpretations with and without
      manual intervention were compared. In 48 tests the computer analysis was not
      modified. In 20 tests canal paresis and directional preponderance changed after
      manual review, but not the final diagnosis. In the remaining 20 tests, manual
      review yielded a different final diagnosis. Computerized ENG provides rapid and
      accurate vestibular studies, but recordings should be reviewed because system
      algorithms sometimes identify other ocular movements as nystagmus.

PMID- 8991401
TI  - [Synthetic implants in the reconstruction of the ossicular chain].
AB  - Experience has revealed a higher rate of functional failure of biocompatible
      prostheses used in the surgical reconstruction of the middle ear than was
      reported initially. The cause of these failures was analyzed in a retrospective
      study of 135 patients who underwent middle ear reconstructive procedures: 47 of
      them involved implantation of plastic prostheses. Proplast or Plastipore, and had
      a sufficient follow-up. We evaluated the prosthetic material and middle-ear
      conditions for which they were implanted.

PMID- 8991402
TI  - [Functional nasal tests for the evaluation of the mucociliary transport].
AB  - A study was made of a noninvasive functional test of mucociliary clearance using
      micronized indigo blue colorant, which is insoluble in airway secretions.
      Transport time to the nasopharynx was measured optically with an endoscope. This
      method was more objective and less irritating than others tested by other
      authors. Measurements were made in each subject using different endoscopes. The
      results were highly suggestive of a difference in nasal mucociliary clearance
      time between healthy and unhealthy subjects. This may mean that chronic
      inflammation, atrophic rhitis, dyskinesia, and other diseases lead to malfunction
      of the nasal mucociliary system.

PMID- 8991403
TI  - [Eosinophils in nasal mucosa of patients with nasal polyps: preliminary
      histochemical study].
AB  - Glycoproteins and glycolipids play an important role in cellular biological
      specificity. The use of lectins as histochemical probes may be useful in studying
      the nasal mucosa. Eosinophils are a common finding in the nasal mucosa of
      patients with nasal polyposis. Histocytochemistry of eosinophils in the nasal
      mucosa of such patients revealed reactivity to all lectins used in this study
      except LTA. This suggests that alpha-L-fucose was not present in the eosinophils
      of the nasal mucosa of patients with nasal polyposis and asthma.

PMID- 8991404
TI  - [Harmonic/noise ratio and spectrographic analysis in vocal abuse pathology].
AB  - Vocal abuse lesions disturb voice production by increasing the presence of noise
      in the voice. The harmonic-to-noise ratio (H/N) and spectrography are two
      different ways to evaluate noise components in the voice. A study was made of 52
      patients (32 polyps, 11 Reinke's edema and 9 nodules) who underwent
      microlaryngeal phonosurgery. The grade of glottic closure was determined by
      stroboscopy; H/N and the long-term average spectrum (LTAS) at low-frequency (0
      2000 Hz) were measured with a CSL-4300 instrument. Stroboscopy and acoustic
      analysis were made before surgery and two week and one month after surgery.
      Before surgery, the LTAS revealed weak harmonics, as shown by H/N values. After
      surgery, H/N values and harmonic energy increased. Preoperative and postoperative
      differences were significant (p < 0.05). Improved glottic closure after surgery
      improved the acoustic parameters.

PMID- 8991405
TI  - [The expression of nuclear proliferation antigen in oropharyngeal carcinoma].
AB  - Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the
      late G1 and S phase of the cell cycle. Immunohistochemical detection of the
      protein is a useful marker of the proliferating cell fraction in tissue
      specimens. A series of 106 oropharyngeal carcinomas were evaluated using the
      streptavidin biotin immunoperoxidase method for detection of this protein. PCNA
      positivity ranged from 9 to 90.2% (mean: 54.86%; SD: 22.05). PCNA results did not
      correlate with clinical or histological parameters. Cox regression analysis
      confirmed the absence of statistical significance of the PCNA index in relation
      to overall survival.

PMID- 8991406
TI  - [Computerized tomography in the detection of metastatic cervical lymph nodes].
AB  - The accuracy of computed tomography (CT) in detecting cervical lymph node
      metastases was studied. Twenty patients with squamous carcinoma of the head and
      neck were selected. The results obtained by cervical palpation, CT and
      postoperative histological study were compared. Palpation had a sensitivity of
      64% and specificity of 100%. CT had a sensitivity of 71% and specificity of 100%.
      The small gain in sensitivity does not justify the systematic use of CT to study
      cervical lymph nodes in head and neck squamous carcinoma.

PMID- 8991407
TI  - [Painful shoulder syndrome with drooping after cervical lymphatic dissection].
AB  - A study was made of 12 patients with head and neck cancer who underwent surgical
      neck dissection in 1993 to evaluate quantitatively the degree of postoperative
      shoulder dysfunction after surgical neck dissection. Nerve conduction studies
      were made of the accessory nerve and the range of motion, strength and position
      of the shoulder were evaluated. Patients were invited to complete a questionnaire
      about daily living activities, shoulder pain, shoulder movement and shoulder
      droop. Our results showed that abnormalities can be found in shoulder and arm
      function after any type of neck dissection and that these are evident when the
      accessory nerve is damaged. Subjective questionnaire findings generally coincided
      with objective postoperative dysfunction.

PMID- 8991408
TI  - [Recurrent parotiditis in adults: review and new therapeutic options].
AB  - Our experience in the management of 20 patients with recurrent parotitis (RP) as
      an isolated symptom is reported. The clinical manifestations in all patients were
      pain, infection and swelling of the parotid gland on at least three separate
      occasions. The presence of obvious tumor or specific inflammation were exclusion
      criteria. Three patients benefited from radiological interventional treatment:
      two stones were removed from the main duct with a Dormia basket and one parotid
      duct stricture was dilated with a balloon catheter. The role of conventional or
      digital sialography and interventional radiology procedures in the diagnosis and
      management of RP is discussed. We proposed this approach as a therapeutic
      alternative to surgery, which is more aggressive and carries a risk of facial
      nerve damage.

PMID- 8991409
TI  - [Intracranial hypertension syndrome due to giant frontoethmoidal osteoma].
AB  - Osteomas are benign lesions that may cause life-threatening complications. Their
      radiological diagnosis usually is casual. Once diagnosed, periodic radiological
      follow-ups should be carried out and if growth occurs, surgical measures should
      be taken to prevent complications. The case of a 53-years-old white male admitted
      for injuries produced by a traffic accident is reported. He had a history of
      frontalization syndrome with episodes of disorientation and behavioral changes.
      Plain radiography, CAT, MRI and bicarotid angiography revealed a bone mass that
      occupied almost the entire anterior fossa. Intracranial hypertension syndrome
      caused by a giant ethmoidal osteoma was diagnosed. Surgery using a frontal
      approach was undertaken.

PMID- 8991410
TI  - [Acute sinusitis, bacteremia and meningitis caused by group F beta-hemolytic
      Streptococcus].
AB  - A 32-year old man without immunodepression developed sinusitis followed by acute
      pyogenic meningitis and beta-hemolytic Streptococcus group F bacteremia.
      Amplicillin treatment produced a favorable outcome with sequela of righ
      neurosensorial deafness. Beta-hemolytic Streptococcus group F meningitis,
      sinusitis and bacteremia is a rare association.

PMID- 8991411
TI  - [Vasculitis caused by Pseudomonas: a case report].
AB  - Pseudomona vasculitis is an exceptional disease. Only a few cases have been
      reported, non with oropharyngeal involvement. The case of a 30-year-old, HIV
      positive man who suddenly developed septicemia and necrotizing lesions with
      tissue destruction of the oropharynx is reported. Histological study confirmed
      vasculitis. Pseudomona aeruginosa was isolated in peripheral blood and in the
      biopsy of the palatal lesion. Antibiotic treatment produced satisfactory results.

PMID- 8991412
TI  - [Follicular carcinoma originating in the lingual thyroid: a case report].
AB  - Follicular carcinoma of a lingual thyroid is unusual, only 25 cases having been
      reported in the literature. We report a case of follicular carcinoma of a lingual
      thyroid. Its clinical and histological features are described and the literature
      is reviewed briefly. Diagnosis and treatment are discussed.

PMID- 8991413
TI  - [Emergency amygdalectomy and adenoidectomy in children with upper respiratory
      obstruction].
AB  - Hypertrophy of the adenoids and tonsils in children sometimes produces life
      threatening upper airway obstruction that requires emergency endotracheal
      intubation followed by adenotonsillectomy. Four patients, age range 18 months to
      3 years, who required emergency treatment in the Pediatric Intensive Care Unit
      were studied for acute respiratory distress syndrome with cyanosis and use of
      accessory respiratory muscles. Two had orotracheal intubation to stabilize their
      cardiorespiratory situation before surgery. One presented cardiomegaly and
      secondary pulmonary arterial hypertension. The third remained stable and
      adequately ventilated with naso-hypopharyngeal ventilation. The fourth remained
      in intensive care for its clinical situation, but did not require exceptional
      measures.

PMID- 8991414
TI  - [Kukuchi's disease of the neck: report of two cases].
AB  - Kikuchi's disease is an unusual disease, described in 1972, that is characterized
      by lymph node enlargement and fever. Cervical lymph nodes are affected so often
      that the ear, nose and throat specialist should be aware of this entity during
      differential diagnosis. Two cases treated in our service are reported and the
      literature is reviewed.

PMID- 8991415
TI  - Reflections on the QDA.

PMID- 8991416
TI  - Congratulations Dr. Pike.

PMID- 8991417
TI  - Lighten up.

PMID- 8991418
TI  - Married to a doctor.

PMID- 8991419
TI  - What's in a name?

PMID- 8991420
TI  - 10th European Anatomical Congress. Florence, September 17-21, 1995. Proceedings
      of the symposium on salivary glands dedicated to Niels Stensen (Niccolo Stenone).

PMID- 8991421
TI  - Inhibition of succinate-ubiquinone reductase by nitrosalicyl-N-alkylamides.
AB  - The abilities of eight nitrosalicyl-N-alkylamides to inhibit succinate-ubiquinone
      reductase were compared. These compounds possess both a nitro group at 3- or 5
      position of the benzyl ring, and a methyl, decyl, dodecyl or tetradecyl group
      subsituted for the amide hydrogen of salicylamide. The result shows the
      following: (a) 3-Nitrosalicyl-N-alkylamides are stronger inhibitors than 5
      nitrosalicyl-N-alkylamides when they have the same alkyl group. (b) The
      inhibitory abilities of both 3-and 5-nitrosalicyl-N-alkylamides increase with
      increasing alkyl group length. (c) Kinetic data show that the inhibition by 3
      nitrosalicyl-N-tetradecylamide is noncompetitive with respect to the electron
      acceptor Q2.

PMID- 8991422
TI  - [3-phase bone scintigraphy: perfusion and vitality of the femur head after media
      femoral neck fracture and osteosynthesis].
AB  - Perfusion and Vitality of the Femoral Head after Medial Neck Fracture and
      Osteosynthesis. AIMS: to analyse with regard to necrosis the perfusion and
      vitality of the femoral head after medial neck fracture and repair by placement
      of a dynamic hip screw. PATIENTS AND METHODS: Twenty-one patients were examined
      by scintigraphy immediately following operation as well as at 3 and 6 months
      postoperative for evaluation of dysfunctions of perfusion and mineralization.
      RESULTS: Complete perfusion and mineralization defects with a tendency for
      revascularization at 3 months will be normal at 6 months. Persisting dysfunctions
      at 3 and 6 months will progress to femoral head necrosis irrespective of the
      fracture staging. CONCLUSIONS: Three-phase skeletal scintigraphy is a highly
      sensitive, non-invasive method for evaluating perfusion and revascularization of
      the femoral head after femoral neck fracture and repair by means of a dynamic hip
      screw. When perfusion of the femoral head is observed one week after the trauma,
      femoral head necrosis will not arise. Immobilization is necessary after partial
      or complete perfusion and mineralization dysfunctions until the scintigraphic
      findings return to normal. The present results may serve as a recommendation for
      loading after fracture repair with a dynamic hip screw.

PMID- 8991424
TI  - [Diagnosis of intraorbital meningioma].
AB  - Demonstration of radiological appearance and the differential diagnosis of
      intraorbital meningeomas in two cases. CT-assisted core needle biopsy offers a
      reliable and easy-to-perform possibility of minimal invasive diagnosis in tumours
      which are difficult to classify.

PMID- 8991423
TI  - [Imaging methods in traumatology of the shoulder- and elbow joint].
AB  - Radiological diagnostics (diagnostic imaging) of the traumatised shoulder and
      elbow joint has expanded considerably and has become increasingly meaningful in
      recent years. The introduction of computed tomography and magnetic resonance
      imaging has enabled a significantly better assessment of soft parts and of the
      inner spatial structure of the joints. Hence, focus of diagnosis has now shifted
      from the assessment of the bones (which was previously the main aspect of
      diagnosis) to a different analysis of the joint as a functional unit of bone and
      soft part structures, an analysis that can also detect subtle changes such as
      additive micro-traumas. The article reviews the conventional imaging methods and
      the present state of the art in tomographic imaging technique, and illustrates
      this by means of several representative examples of diagnostic imaging.

PMID- 8991425
TI  - [Early pulmonary changes caused by amiodarone].
AB  - Confluent infiltrates and interstitial condensates with (sub)segmentary spreading
      are typical radiological findings in amiodarone pneumopathy. A case is presented
      where daily amounts of 200-600 mg and a total of 18.3 g amiodarone led to
      alveolitis with fibrosis within 4 weeks, which is uncommon in the early stage.

PMID- 8991426
TI  - [Value of percutaneous catheter cholangiography in postoperative biliodigestive
      and bilio-biliary anastomoses].
AB  - AIM OF STUDY: To examine the relative importance of percutaneous catheter
      cholangiography in postoperative diagnostics after biliary reconstruction.
      METHODS: 55 patients (33 males, 22 females) were subjected to 101 catheter
      cholangiographies. 30-50 ml of a water-soluble, iodic contrast medium were
      administered via an infusion system. Initial examinations were performed between
      the 3rd and 7th day following operation, while follow-up examinations were
      executed between the 8th and 145th day after surgery. The position of the
      catheter, the function of the anastomosis, the filling of the biliary ducts and
      the discharge of the contrast medium were assessed. RESULTS: 45 examinations were
      inconspicuous. Drainage obstruction of the contrast medium was observed in 24
      cases. Filling defects were observed in 8 examinations. A dislocation of the
      catheter was encountered in 5 cholangiographies while 19 examinations displayed a
      bile leak. CONCLUSION: Percutaneous catheter cholangiographies can be used to
      detect postoperative complications following biliary reconstruction in an easy,
      reliable, and cost-effective manner that also does not put too much strain on the
      patient. Indications for the implementation of catheter cholangiographies are the
      occurrence of abdominal complaints, the clinical appearance of a peritonitis, or
      an increase of the serum bilirubin value. Routine examinations are recommended in
      conditions following liver transplantations. In addition to this, a
      cholangiography should be carried out prior to the removal of the catheter.

PMID- 8991427
TI  - [Risk of hyperthyroidism in examinations with contrast media].
AB  - Investigations with contrast media inevitably lead to the patient being exposed
      to large amounts of iodine. Under certain preconditions this gentails danger for
      the patient by causing either iodine-induced hyperthyroidism, which is difficult
      to treat, or even a thyrotoxic crisis. Patients with normal thyroid function and
      size have only minute changes of thyroid hormones and TSH within the normal range
      and are not at risk. Patients with unknown hyperthyroidism--independent of the
      etiological form--and patients with functional autonomy are at risk of
      exacerbation of pre-existing hyperthyroidism or development of iodine-induced
      hyperthyroidism. This development depends on two factors: a) the volume of
      autonomous tissue and b) the quantity of iodine exposure. Besides contrast media,
      other sources of iodine excess are possible, such as iodine-containing
      disinfectants, secretolytic agents, antiarrhythmics like amiodarone, eye drops
      and ointments, geriatrics, skin ointments, toothpaste etc. The development of
      hyperthyroidism can be prevented by combined treatment with antithyroid drugs and
      perchlorate in the case of preexisting hyperthyroidism or the urgent clinical
      suspicion of thyrotoxicosis or with perchlorate alone, when the patients is
      euthyroid and does not have a large nodular goitre.

PMID- 8991428
TI  - [Comparative roentgenometry of the hand in aging].
AB  - Increasing age is a risk factor for the development of osteoarthrosis of the
      joints of the hand in adults between 21 and 60 years of age. Only in the very old
      (> or = 80 years) is osteoarthrosis of the hand part of the age related
      degeneration. The literature contains different parameters and indices
      correlating the amounts of minerals and ashes of metacarpal bones. Our results
      speak in favour of the presumptions published by Exton-Smith et al. (1969 b) that
      bone mass belongs among the biological characteristics of old age. Our
      investigations of hand roentgenograms reveal that remodeling of the joint socket
      as described by pathologists is not a general but an elective phenomenon. With
      age the wrist shows only an increasing angle of the radial joint surface (males,
      right hand) and there is a variation of form in the medial sesamoid bone at the
      first metacarpus (males, left hand).

PMID- 8991429
TI  - [Color coded ultrasound--quantification of perfusion in a perfusion model].
AB  - This experimental study demonstrates the quantification of perfusion in a phantom
      simulating tissue using a computer-assisted interpretation. The parameters flow
      volumin, velocity (defined by pulse-repetition-frequency-PRF), and the time of
      adding up peaks were varied. The detected color-coded pixels determine the flow
      area as a percentage of the ground area and the frequency with the highest pixel
      density. The width is the area between the highest and lowest detected
      frequencies. The flow area correlates with the perfusion rate (r > or = 0.97). To
      detect low perfusions, a slow velocity and extended Peak Hold-function are
      necessary. Peaks with a high frequency superpose those with lower frequencies, so
      that these signals are not available for the interpretation. To determine the
      width or the frequency with highest pixel density a short Peak Hold-function must
      be chosen. When changing the velocity, these quantities are also changed, so that
      standards are necessary. This study shows a correlation between a defined
      perfusion in a phantom-simulating tissue and the flow area. It suggests a
      possibility to quantify flow in different organs. One aim would be to determine
      abnormal vascularisation, for example, in tumours of the liver or breast.

PMID- 8991430
TI  - [Synovial sarcoma of the foot].
AB  - The case of a 29 year-old female patient who had experienced pain in the right
      midfoot for 5 years which was diagnosed as a degenerative or rheumatic change and
      treated by physiotherapy and medication. By means of magnetic resonance imaging
      we identified a soft-tissue tumor of the midfoot. Histology provided the findings
      of a monophasic fibrous synovial sarcoma. The case history is reported together
      with a presentation of the disease and its radiological diagnosis.

PMID- 8991431
TI  - [Tuberculous pseudotumor of the omentum].
AB  - The abdomen is one of the most common extrathoracic manifestation sites for
      tuberculosis. The constellation of ascites, fatigue, fever, weight loss and ileus
      in younger patients should lead to the diagnosis, particularly in times when
      immunosuppression appears more frequently associated with AIDS. Using modern
      imaging techniques like CT and ultrasound and in combination with interventional
      procedures (guided paracentesis or biopsy) the number of diagnostic laparotomies
      and laparoscopies, like in the case presented could be reduced. In this context
      the radiologist should include tuberculosis in the differential diagnosis.

PMID- 8991432
TI  - [Which damping body for evaluating the uniformity of the intensification factor
      of roentgen cassettes?].

PMID- 8991433
TI  - [Infections and granulocyte colony-stimulating factor (G-CSF)].

PMID- 8991434
TI  - [Digestive cytomegalovirus disease in AIDS patients].
AB  - BACKGROUND: In this paper we study the digestive manifestations of
      cytomegalovirus (CMV) in AIDS patients. Also, we evaluate the antiviral treatment
      and the necessity of maintenance therapy. METHODS: Retrospective review of
      medical charts of all patients with AIDS and digestive CMV disease diagnosed and
      followed-up since 1983 to december 1993. RESULTS: Of 720 AIDS patients, 96
      presented a CMV disease. Among them, 30 patients (31%) complained digestive
      manifestations. These were 26 males and 4 females, mean age: 37.4 y-old. Risk
      factors for HIV were: 13 homosex and 12 intravenous drug abusers. Average of time
      between AIDS diagnosis and digestive CMV disease: 13.4 months. Fourteen patients
      had esophagitis, 9 proctocolitis, 3 hepatitis, 3 pancreatitis, 2 gastric
      ulcerations, one small bowel disease and other an oral ulceration. Two patients
      had a concomitant CMV chorioretinitis. CD4 lymphocytes were below 0.05 x 10(9)/l
      in 29 patients. Twenty-four patients received antiviral treatment during the
      acute disease period, with a clinical curation rate of 60%. Seven patients
      received maintenance therapy and remained free of CMV disease until death. Eleven
      patients didn't received maintenance treatment. Of them, one patient presented a
      digestive relapse and two developed a CMV chorioretinitis. Mortality in the first
      month from diagnosis was 23% and the median of survival time for patients who
      cured and initial episode of digestive CMV disease was 208 days, wether or not
      the patient received maintenance therapy or not. CONCLUSIONS: One third of ours
      patients with AIDS and CMV infection have a digestive disease. This CMV digestive
      disease appears in patients with a severe immunosuppression. Acute phase
      mortality was 23%. The median survival was 7 months, independently or receiving
      maintenance treatment or not.

PMID- 8991435
TI  - [Clinical characteristics and epidemiologic study of a listeriosis outbreak in
      Grand Canary].
AB  - BACKGROUND AND METHODS: Human infections caused by Listeria monocytogenes often
      present as sporadic cases without any epidemiological relationship among them;
      however they also appear as outbreaks that are usually detected by an increase in
      the number of cases diagnosed by hospitals of the geographic area. Between
      December 1991 and May 1993, twenty four cases of listeriosis were detected in
      three hospitals of Las Palmas de Gran Canaria; and they were classified as an
      outbreak. Our report describes its clinical, epidemiological and microbiological
      aspects. RESULTS AND CONCLUSIONS: Twenty four cases of listeriosis were
      diagnosed, 12 occurred in pregnant women or neonates (5 and 7 respectively) and
      12 in non pregnant adults. All adult infections were community-acquired. The
      incidence rate was, for the epidemic area, 76.3 cases per million population
      during the period considered (18 months). Among non pregnant adults, 9/12
      patients had some underlying disease and 9/12 presented CNS affection (meningitis
      and/or cerebritis). In the group of pregnant women, 4 cases occurred in the
      second trimester and fetal loss was caused; one case was detected in the third
      trimester and four weeks later the patient delivered an unaffected infant. All
      cases of neonatal listeriosis presented as early-onset sepsis. Of the 24 strains
      of L. monocytogenes, 21 were serotype 4, two were serotype 1 and one was not
      typeable. Strains from 12 patients were available for epidemiological analysis,
      seven of which corresponded to the same pattern and there were three more
      different patterns.

PMID- 8991436
TI  - [Activity of erythromycin and clarithromicin against isolates of Streptococcus
      pneumoniae with decreased sensitivity to penicillin obtained from healty
      carriers. Spanish Collaborative Group].
AB  - BACKGROUND: Empirical treatment of pneumococcal upper and lower respiratory
      infections must be chosen on the basis of the susceptibility patterns of
      nasopharyngeal colonizing strains isolated from healthy carriers. METHODS: The
      susceptibility to erythromycin and clarithromycin was investigated by a
      conventional microdilution method among 103 pneumococci isolates recovered from
      healthy children (n = 63) and adults (n = 40) exhibiting decreased susceptibility
      to penicillin (MIC > or = 0.12 mg/l). RESULTS: 63% of penicillin -resistant
      pediatric isolates were susceptible to erythromycin and 78.9% were susceptible to
      clarithromycin . Among isolates with diminished susceptibility to penicillin ,
      77.7% were susceptible to erythromycin and 86.3% to clarithromycin . 90% of adult
      isolates were susceptible to erythromycin and to clarithromycin . Overall,
      clarithromycin exhibited a better activity than erythromycin . CONCLUSIONS:
      Clarithromycin , and to a lesser extent erythromycin , are good alternatives to
      penicillin in the empirical treatment of respiratory tract infections caused by
      pneumococci with diminished susceptibility to penicillin .

PMID- 8991437
TI  - [Intervention in a measles outbreak].
AB  - BACKGROUND: The description of a community measles epidemic and the activities
      developed to control the same is presented. Vaccination efficacy was studied by a
      cases and controls study. METHODS: The study period of the epidemic was from
      August 1994 to March 1995 and the intervention was performed from January to
      March 1995. The activities were developed in two phases: the first directed at a
      descriptive study and control of the outbreak and in the second phase a cases and
      controls study was designed to evaluate vaccination efficacy (VE%) versus
      measles. RESULTS: A total of 325 cases of measles were registered over a period
      of 29 weeks. The greatest attack rate was found in the age group of 5 to 9 years
      with 5-91 cases/100. The surveillance system and the priorization of activities
      protocol designed for control of the outbreak were found to be useful. The result
      of the cases and controls study demonstrated VE% to be 93.5% (84.3-97.3%).
      CONCLUSIONS: Rapid intervention in the outbreaks of measles is considered
      fundamental to avoid propagation of the same among the susceptible population.
      The surveillance system versus the disease should therefore be optimized.
      Although vaccination efficacy was found to be good, the high rates of attack
      found in the theoretically vaccinated groups lead to the recommendation of the
      introduction of a second dosis of the vaccine and to vaccinate the existing non
      vaccinated sets.

PMID- 8991438
TI  - [Use of DNA sequence hybridization with specific oligonucleotide probes to
      identify hepatitis C virus genotypes].
AB  - BACKGROUND: Recent development of an assay based on the hybridization of the
      amplification product obtained by polymerase chain reaction (PCR) of the RNA of
      hepatitis C virus (HCV) with specific probes for each viral genotype ("reverse
      hybridization"), has permitted to have a rapid, simple and reproductible
      technique to identify the different genotypes of HCV. The identification of HCV
      genotypes seems to be important given their different pathogenic capacity and
      response to interferon therapy. METHODS: We prospectively studied 221 patients
      with HCV infection defined by the detection of viral RNA in serum by "nested
      PCR". HCV genotype was determined by "reverse-hybridization" using specific
      oligonucleotide-probes for each genotype corresponding to the 5, UTR. RESULTS:
      HCV 1b genotype was predominant in 221 patients studied (180/221, 81%), followed
      by 1a (10%) and by 3 and 4 (4% respectively). Two patients presented mixed
      infection (1a/1b). No case of infection by genotypes 2 and 5 was found. The
      predominance of 1b genotype was more evident in adults than in children (83 vs
      62%) (p < 0.05). CONCLUSIONS: HCV 1b is the predominant genotype among our
      patients with hepatic disease induced by HCV. The reverse-hybridization assay is
      a simple and rapid technique that permit the identification of the most important
      genotypes of hepatitis C virus.

PMID- 8991439
TI  - [Bacteremia caused by Alcaligenes (Achromobacter) xylosoxidans. Description of 3
      cases and review of the literature].
AB  - BACKGROUND: Alcaligenes (Achromobacter) xylosoxidans occasionally cause
      infections, mainly in immunocompromised hosts. METHODS: Three cases of bacteremia
      due to A. xylosoxidans observed at the Fundacion Jimenez Diaz between 1985-1994
      were described. Moreover, 38 single cases of bacteremia due to A. xylosoxidans
      and 21 episodes associated with outbreak were reviewed by using computerized
      bibliography data base MEDLINE (1970-december 1994). RESULTS: From 41 patients
      with bacteremia (including our 3 cases) reviewed, 27 were immunosuppressed hosts
      (twenty had neoplasia disease). The most common clinical presentation was primary
      bacteremia (11 cases, 27%) and pneumonia (10, 24%), followed by catheter
      associated bacteremia (8, 20%), meningitis (4), bacteremia from abdominal cavity
      (4), endocarditis (3) and pyelonephritis (1). The mortality rate was higher
      (39%), specially in patients whom were a intensive care unit acquisition (87%),
      and illness with endocarditis (100%). No patient with catheter-related bacteremia
      died. All of 21 outbreak episodes of bacteremia had a autolimited form and low
      mortality (4.8%). CONCLUSION: A. xylosoxidans is a microorganism with
      demonstrated capacity of cause bacteremia, mainly in immunocompromised hosts,
      with high mortality rates. Sometimes, it causes outbreaks of bacteremia with low
      mortality.

PMID- 8991440
TI  - [Variation of the incidence and antibiotic sensitivity of Neisseria gonorrhoeae
      in a 7-year period].
AB  - BACKGROUND: The aim of this study was to determine the incidence and antibiotic
      sensitivity of Neisseria gonorrhoeae versus penicillin, tetracycline, cefoxitin,
      ceftriaxone and spectinomycin from 1988 to 1994 in the province of Soria (Spain).
      METHODS: From January 1988 to December 1994, clinical samples of 57 strains of N.
      gonorrhoeae were isolated. Auxotype, serotype, and minimum inhibitory
      concentration (MIC) studies were performed versus 5 antimicrobials and analysis
      of plasmids in the penicillinase producer strains (PPNG), was carried out in the
      Bacteriology Department of the Instituto Carlos III in Madrid (Spain). RESULTS:
      The rate of incidence of the isolation of N. gonorrhoeae was similar from 1988 to
      1990 (11.7 to 19.1 cases per 100,000 inhabitants) and decreased from 1991 to 1994
      (6.4 to 0 cases per 100,000 inhabitants). The strains belonged to 30 different
      auxotypes/serotypes indicating a great heterogeneity among them. The proportion
      of penicillinase producing N. gonorrhoeae (PPNG) increased over the study period.
      The first strains with high resistance to tetracycline (TRNG) were first isolated
      in the authors' area in 1991 and the proportion increased up to the end of the
      study. All the strains were sensitive to ceftriaxone, cefoxitin and
      spectinomycin. CONCLUSIONS: A decrease was observed in the rate of incidence of
      N. gonorrhoeae since 1991 with an increase in the proportion of NGPP and TRNG
      strains. Ceftriaxone and spectinomycin present good activity versus all the
      strains studied with their empiric use as treatment being possible in the
      province of Soria (Spain).

PMID- 8991441
TI  - [Gynecological complications in HIV-positive women].

PMID- 8991442
TI  - [Encrusted papules and subcutaneous nodules in a linear distribution].

PMID- 8991443
TI  - [Lytic lesion of the distal phalanx of a patient with systemic circumscribed
      sclerosis].

PMID- 8991445
TI  - [Subacute endophthalmitis caused by Corynebacterium group 1].

PMID- 8991444
TI  - [Disseminated candidiasis and endophthalmitis caused by Candida tropicalis].

PMID- 8991446
TI  - [Septic arthritis caused by Erysipelothrix rhusiopathiae].

PMID- 8991447
TI  - [Myiasis caused by Dermatobia hominis].

PMID- 8991448
TI  - [Saccharomyces cerevisiae vaginitis].

PMID- 8991449
TI  - [Polymicrobial endocarditis in an intravenous drug addict with isolation of
      Eikenella corrodens].

PMID- 8991450
TI  - [Pneumonia caused by measles in a pregnant woman with HIV antibodies. Response to
      treatment with immunoglobulins].

PMID- 8991451
TI  - [Cellulitis and lymphangitis caused by Staphylococcus lugdunensis].

PMID- 8991452
TI  - [Bacteremia caused by Enterococcus avium secondary to thrombosis of the lateral
      sinus and the internal jugular vein].

PMID- 8991453
TI  - [Bordetella bronchiseptica in a patient with prostatic adenocarcinoma].

PMID- 8991454
TI  - Low-dimensional chaotic attractors in the rat brain.
AB  - The existence of chaotic attractors for discrete time series, derived from the
      occurrences of spikes during electrophysiological recordings, was investigated.
      The time series included between 800 and 5200 points per analyzed record. The
      spike trains were recorded in the substantia nigra pars reticulata (n = 13) and
      in the auditory thalamus (n = 14). The experiments were performed on anesthetized
      rats during spontaneous activity and during auditory stimulation. According to
      standard methods of dynamical systems theory, an embedding space was constructed
      using delay coordinates. The embedding and correlation dimensions were computed
      by means of the correlation integrals. For 7 of 27 samples, a deterministic
      structure with a low embedding dimension (ranging between 2 and 6) and a
      correlation dimension between 0.14 and 3.3 could be determined. Evidence was
      found that the sensory stimulation may affect the chaotic behavior. Single units
      recorded simultaneously from the same electrode tip may display different chaotic
      dynamics, even with a similar time-locked response to the stimulus onset.

PMID- 8991455
TI  - Low-dimensional dynamic self-organization in delta-sleep: effect of partial sleep
      deprivation.
AB  - Studies on extended data including 37 electroencephalographic (EEC) records of
      delta-sleep, each 10(3) s long (six subjects: up to seven nights per subject,
      comprising normal sleep, partial deprivation and recovery), confirmed earlier
      conclusions that rare episodes of low-dimensional dynamic self-organization, with
      life-times between 10 and 20 s, are present in stage 4 sleep. Particular care was
      taken of the Theiler correction which, in some delta-sleep signals, required the
      deletion of trajectory points covering nearly one pseudo-period. The percentage
      of segments showing an episode, i.e. the attractor probability, decreased with a
      change in sleep conditions either deprivation or recovery prior to the next
      deprivation. Repetition of deprivation over three nights resulted in an
      adaptation process, manifested by an increase in attractor probability. After the
      sharp decrease in probability observed when recovery was established prior to the
      next deprivation, and on return to normal conditions of sleep at 2200 hours, the
      probability was immediately close to that observed in normal baseline sleep
      conditions free of any interference. The observation of a definite effect of
      sleep deprivation and recovery upon the number of stage 4 attractors observed
      provides a line of approach to the physiological significance of the probability
      of such attractors.

PMID- 8991456
TI  - Visual computation of egomotion using an image interpolation technique.
AB  - A novel technique is presented for the computation of the parameters of egomotion
      of a mobile device, such as a robot or a mechanical arm, equipped with two visual
      sensors. Each sensor captures a panoramic view of the environment. We show the
      parameters of ego-motion can be computed by interpolating the position of the
      image captured by one of the sensors at the robot's present location, with
      respect to the images captured by the two sensors at the robot's previous
      location. The algorithm delivers the distance travelled and angle rotated,
      without the explicit measurement or integration of velocity fields. The result is
      obtained in a single step, without any iteration or successive approximation.
      Tests of the algorithm on real and synthetic images reveal an accuracy to within
      5% of the actual motion. Implementation of the algorithm on a mobile robot
      reveals that stepwise rotation and translation can be measured to within 10%
      accuracy in a three-dimensional world of unknown structure. The position and
      orientation of the robot at the end of a 30-step trajectory can be estimated with
      accuracies of 5% and 5 degrees, respectively.

PMID- 8991458
TI  - Identification of the nonlinear state-space dynamics of the action-perception
      cycle for visually induced postural sway.
AB  - Human subjects standing in a sinusoidally moving visual environment display
      postural sway with characteristic dynamical properties. We analyzed the
      spatiotemporal properties of this sway in an experiment in which the frequency of
      the visual motion was varied. We found a constant gain near 1, which implies that
      the sway motion matches the spatial parameters of the visual motion for a large
      range of frequencies. A linear dynamical model with constant parameters was
      compared quantitatively with the data. Its failure to describe correctly the
      spatiotemporal properties of the system led us to consider adaptive and nonlinear
      models. To differentiate between possible alternative structures we directly
      fitted nonlinear differential equations to the sway and visual motion
      trajectories on a trial-by-trial basis. We found that the eigenfrequency of the
      fitted model adapts strongly to the visual motion frequency. The damping
      coefficient decreases with increasing frequency. This indicates that the system
      destabilizes its postural state in the inertial frame. This leads to a faster
      internal dynamics which is capable of synchronizing posture with fast-moving
      visual environments. Using an algorithm which allows the identification of
      essentially nonlinear terms of the dynamics we found small nonlinear
      contributions. These nonlinearities are not consistent with a limit-cycle
      dynamics, accounting for the robustness of the amplitude of postural sway against
      frequency variations. We interpret out results in terms of active generation of
      postural sway specified by sensory information. We derive also a number of
      conclusions for a behavior-oriented analysis of the postural system.

PMID- 8991457
TI  - Computer simulation of shared input among projection neurons in the dorsal
      cochlear nucleus.
AB  - Computer simulations of a network model of an isofrequency patch of the dorsal
      cochlear nucleus (DCN) were run to explore possible mechanisms for the level
      dependent features observed in the cross-correlograms of pairs of type IV units
      in the cat and nominal type IV units in the gerbil DCN. The computer model is
      based on the conceptual model (of a cat) that suggests two sources of shared
      input to DCN's projection neurons (type IV units): excitatory input for auditory
      nerves and inhibitory input from interneurons (type II units). Use of tonal
      stimuli is thought to cause competition between these sources resulting in the
      decorrelation of type IV unit activities at low levels. In the model, P-cells
      (projection neurons), representing type IV units, receive inhibitory input from I
      cells (interneurons), representing type II units. Both sets of model neurons
      receive a simulated excitatory auditory nerve (AN) input from same-CF AN fibers,
      where the AN input is modeled as a dead-time modified Poisson process whose
      intensity is given by a computationally tractable discharge rate versus sound
      pressure level function. Subthreshold behavior of each model neuron is governed
      by a set of normalized state equations. The computer mode has previously been
      shown to reproduce the major response properties of both type IV and type II
      units (e.g., rate-level curves and peri-stimulus time histograms) and the level
      dependence of the functional type II-type IV inhibitory interaction. This model
      is adapted for the gerbil by simulating a reduced population of I-cells.
      Simulations were carried out for several auditory nerve input levels, and cross
      correlograms were computed from the activities of pairs of P-cells for a complete
      (cat model) and reduced (gerbil model) population of I-cells. The resultant
      correlograms show central mounds (CMs), indicative of either shared excitatory or
      inhibitory input, for both spontaneous and tone-evoked driven activities. Similar
      to experimental results, CM amplitudes are a non-monotonic function of level and
      CM widths decrease as a function of level. These results are consistent with the
      hypothesis that shared excitatory input correlates the spontaneous activities of
      type IV units adn shared inhibitory input correlates their driven activities. The
      results also suggest that the decorrelation of the activities of type IV units
      can result from a reduced effectiveness of the AN input as a function of
      increasing level. Thus, competition between the excitatory and inhibitory inputs
      is not required.

PMID- 8991459
TI  - Organization of receptive fields in networks with Hebbian learning: the
      connection between synaptic and phenomenological models.
AB  - In this paper we address the question of how interactions affect the formation
      and organization of receptive fields in a network composed of interacting neurons
      with Hebbian-type learning. We show how to partially decouple single cell effects
      from network effects, and how some phenomenological models can be seen as
      approximations to these learning networks. We show that the interaction affects
      the structure of receptive fields. We also demonstrate how the organization of
      different receptive fields across the cortex is influenced by the interaction
      term, and that the type of singularities depends on the symmetries of the
      receptive fields.

PMID- 8991460
TI  - Recognition and tracking of impulse patterns with delay adaptation in biology
      inspired pulse processing neural net (BPN) hardware.
AB  - The application of an electronic real time emulator for biology-inspired pulse
      processing neural networks (BPN) to recognition and temporal tracking of discrete
      impulse patterns via delay adaptation is demonstrated. The electronic emulation
      includes biologically plausible features, such as asynchronous impulses, membrane
      potentials and adaptive weights, as well as a mechanism to modify signal delays.
      The rule for the adaptation of impulse propagation delays is as follows: 'error
      neurons' detect temporal differences between single impulses of other neurons and
      adjust corresponding signal delay parameters. In the application presented BPN
      adapts its time delays in order to form a finely tuned match with a given
      sequence of three discrete impulses. After learning, BPN is capable not only of
      highly selective recognition of the learned impulse pattern but also of tracking
      a gradually changing impulse pattern. Tracking is achieved by continuously re
      adjusting the delay profile. Delay adaptation (rather than weight adaptation)
      appears to be the more effective mechanism for such application.

PMID- 8991461
TI  - Numerical simulation of excitation-contraction coupling in a locus of the small
      bowel.
AB  - A mathematical model for the excitation-contraction coupling within a functional
      unit (locus) of the small bowel is proposed. The model assumes that: the
      functional unit is an electromyogenic syncytium; its electrical activity is
      defined by kinetics of L- and T-type Ca(2+)-channels, mixed Ca(2+)-dependent K(+)
      channels, potential-sensitive K(-)channels and Cl(-)-channels; the basic neural
      circuit, represented by the cholinergic and adrenergic neurones, provides a
      regulatory input to the functional unit via receptor-linked L-type Ca(2+)
      channels; the smooth muscle syncytium of the locus is a null-dimensional
      contractile system. With the proposed model the dynamics of active force
      generation is determined entirely by the concentration of cytosolic calcium. The
      model describes electrical processes of the propagation of excitation along the
      neural circuit, chemical mechanisms of nerve-pulse transmission at the synaptic
      zones and the dynamics of active force generation. Numerical simulations have
      shown that it is capable of displaying different electrical patterns and
      mechanical responses of the locus. The simulated effects of tetrodotoxin, beta
      bungarotoxin, salts of divalent cations, inhibitors of catechol-O
      methyltransferase and neuronal uptake mechanisms, and changes in the
      concentration of external Ca2+ on the dynamics of force generation have been
      analysed. The results are in good qualitative and quantitative agreement with
      results of experiments conducted on the visceral smooth muscle of the small
      bowel.

PMID- 8991462
TI  - Neural computations underlying the exertion of force: a model.
AB  - We have developed a model that simulates possible mechanisms by which supraspinal
      neuronal signals coding forces could converge in the spinal cord and provide an
      ongoing integrated signal to the motoneuronal pools whose activation results in
      the exertion of force. The model consists of a three-layered neural network
      connected to a two-joint-six-muscle model of the arm. The network layers
      represent supraspinal populations, spinal cord interneurons, and motoneuronal
      pools. We propose an approach to train the network so that, after the synaptic
      connections between the layers are adjusted, the performance of the model is
      consistent with experimental data obtained on different organisms using different
      experimental paradigms: the stiffness characteristics of human arm; the structure
      of force fields generated by the stimulation of the frog's spinal cord; and a
      correlation between motor cortical activity and force exerted by monkey against
      an immovable object. The model predicts a specific pattern of connections between
      supraspinal populations coding forces and spinal cord interneurons: the weight of
      connection should be correlated with directional preference of interconnected
      units. Finally, our simulations demonstrate that the force generated by the sum
      of neural signals can be nearly equal to the vector sum of forces generated by
      each signal independently, in spite of the complex nonlinearities intervening
      between supraspinal commands and forces exerted by the arm in response to these
      commands.

PMID- 8991463
TI  - 2nd Annual meeting of the International Society of the Advancement of Respiratory
      Psychophysiology (ISARP). Toronto, Canada, 9-11 October 1995. Abstracts.

PMID- 8991464
TI  - [The role of the anesthetist or what do patients know about us?].

PMID- 8991465
TI  - [Alpha 2-adrenoreceptor agonists--horse or donkey?].

PMID- 8991466
TI  - [Mucociliary clearance function and medicamentous modification].
AB  - Mucociliary clearance represents a complex self-cleaning mechanism of the lung
      and is based on the functional unity of ciliated columnar cells and the special
      viscoelastic properties of the secretion produced in the tracheobronchial system.
      It has been known for a long time that intubation and mechanical ventilation can
      impair mucous transport and lead to morphological damage to the tracheobronchial
      mucosa. Recent studies made it clear, however, that mechanical ventilation during
      anaesthesia using an appropriate anaesthesiological technique has no deleterious
      effect on mucus transport in patients with healthy lungs. Ventilated patients in
      the intensive-care unit frequently have impaired mucus transport, which is
      associated with the development of retention of secretion and nosocomial
      pneumonia. In these patients a number of factors combine to form a formidable
      potential insult to the mucociliary transport mechanism. Numerous drugs can
      affect mucociliary transport. Beta-mimetics and theophylline, in particular, have
      a favourable effect on mucociliary transport, whereas the effect of mucolytic
      agents is controversial.

PMID- 8991467
TI  - [Patient knowledge concerning anesthesia general practice and the
      responsibilities of the anesthetist].
AB  - In two Austrian university hospitals 104 patients were interviewed on the basis
      of questionnaires about their knowledge of the role of anaesthetists. Although
      93% of the Patients considered anaesthesists to be physicians, major deficits
      were found regarding the knowledge about the spheres of activities of
      anaesthetists. 60% of the respondents confined the anaesthetist to the operating
      theatre. Only 55% considered the anaesthetist responsible for their safe recovery
      from anaesthesia. Previous anaesthesia showed to have no influence on the
      knowledge of anaesthesia practice and the role of anaesthetists. To current
      practice of informing the patient calls for improvement and new approaches. In
      addition to this further evaluation work on the influence of the mass media and
      public knowledge about anaesthesia and the anaesthetists' role should be
      undertaken.

PMID- 8991468
TI  - [Does propofol have advantages over isoflurane for sufentanil supplemented
      anesthesia in children for strabismus surgery?].
AB  - OBJECTIVE: The present study investigates the effectivity and the incidence of
      side effects of sufentanil-supplemented propofol versus isoflurane anaesthesia in
      children undergoing elective strabismus surgery. METHODS: 130 children (aged 3
      11; ASA I-II) were randomly allocated to one of four groups. In group 1 and 2,
      anaesthesia was induced with 2 mg/kg propofol and maintained with 15-20 mg/kg x h
      propofol and 30% O2 in air (group 1) or 10-15 mg/kg x h propofol in N2O (group
      2). After induction with either 2 mg/kg propofol (group 3) or 5 mg/kg thiopentone
      (group 4), anaesthesia was maintained with 0.8-1.5 Vol% isoflurane and N2O in 30%
      O2 in these groups. All children were orally premedicated with midazolam and
      atropine and received a single dose of intravenous sufentanil (0.5 micrograms/kg)
      and atracurium (0.5 mg/kg) prior to intubation. Heart rate, mean arterial blood
      pressure and pulse oximetry were registered 5 min prior and after intubation as
      well as 10 min before and 5 min after extubation. The incidence of pain and
      involuntary movements during injection, oculocardiac reflex (OCR), laryngospasm
      and postoperative shivering were as well registered as the duration of the
      operation and the time of extubation. Episodes of nausea and vomiting were
      documented during 24 hours postoperatively. RESULTS: TIVA with Propofol resulted
      in a decreased heart rate (p = 0.002) and a higher frequency of OCR (p = 0.01)
      than thiopentone/isoflurane anaesthesia with a higher sensitivity of children
      younger than 6 years (p = 0.007) in all groups. There were no differences in
      extubation time between groups. The overall incidence of nausea (p = 0.002) and
      vomiting (p = 0.007) was lower in group 1 and 2 when compared to group 3 and 4.
      CONCLUSION: Propofol as an induction agent of balanced anaesthesia fails to show
      advantages over thiopentone. During total intravenous anaesthesia propofol
      increases the risk of bradycardia especially in younger children. However, a
      significantly lower incidence of postoperative nausea and vomiting after TIVA
      with propofol and sufentanil, irrespective of N2O administration, may be an
      advantage over isoflurane anaesthesia in paediatric patients after strabismus
      surgery.

PMID- 8991469
TI  - [Ventilation via a transnasally placed pharyngeal tube. Comparison with mask
      ventilation].
AB  - OBJECTIVE: The present prospective study was designed to investigate the
      respiratory function during ventilation via a tube inserted through the nose into
      the pharynx. Results were compared with respiratory parameters measured during
      conventional mask ventilation in the same patients. METHODS: 20 ASA physical
      status I-II patients were studied after approval by the local Ethics Committee.
      Anaesthesia was induced with alfentanil 15 micrograms/kg and propofol 2.5-3.0
      mg/kg and maintained with propofol, 12-15 mg/kg/h. Patients were ventilated via a
      facemask with oxygen and a tidal volume of approximately 8ml/kg (measurement A).
      After insertion of a tube (I.D. 7.0-7.5 mm) through the nostril into the pharynx
      ventilation was repeated in the same manner (measurement B). To secure airway
      seal a second person closed the patient's mouth and exerted cricoid pressure.
      Following neuromuscular blockade with suxamethonium (1.5 mg/kg) respiratory
      parameters were measured again (C). Measurements included pulse oximetry and side
      stream spirometry with continuous collection of the following data: airway
      pressure, inspired and expired tidal volume, dynamic compliance, expired volume
      in one second, inspiratory and expiratory oxygen and carbon dioxide
      concentration. Pressure-volume and flow-volume loops were displayed continuously.
      RESULTS: Ventilation via facial mask or via pharyngeal tube with and without
      relaxation showed normal endtidal FECO2. The mean values were 4.5 +/- 0.7%, 4.8
      +/- 0.4% and 4.6 +/- 0.7%, respectively. Mean oxygen saturation exceeded 98% in
      each period. Leakage during mask ventilation was 59.3 +/- 65.5 mL and decreased
      to 40.5 +/- 62.1 mL with the pharyngeal tube, whereas relaxation resulted in a
      significant increase to 92.3 75.0 mL. Compliance (Cdyn) and expired volume in one
      second (V 1.0) did not change significantly during the entire period of
      measurement. CONCLUSION: The use of a pharyngeally placed tube proved adequate
      compared to conventional mask ventilation in 20 patients without underlying
      airway disease.

PMID- 8991470
TI  - [Behm's T-piece for reducing anesthesia gas pollution at the anesthesia work
      site].
AB  - The safety standards demanded for performing anaesthesia and the increasing
      burden of work to be handled by OP personnel entail continuous supervision and
      elimination of hazards and leaks. One example illustrates this necessity:
      Anaesthetic agents in the circular system of the induction are pollute the
      atmosphere after disconnection of one patient and transport into the OP suite and
      are a potential risk to personnel and next patient. C. Behm developed a T-piece
      which connects the Y-piece with the scavenging system leading to elimination of
      residual anaesthetics from the circular system. A useful byproduct is the longer
      life of the galvanic O2 sensor.

PMID- 8991471
TI  - [Albumin as volume replacement: pro].

PMID- 8991472
TI  - [Albumin as volume replacement: contra].

PMID- 8991473
TI  - [The recommendation by Menzel in 1877 for statistical assessment of anesthesia
      performance].

PMID- 8991474
TI  - [Lymphangiomatosis as the cause of therapy refractory chylothorax and ascites].
AB  - After five weeks of progressing dyspnoea and pain in the lower abdomen a 44-year
      old woman was admitted in our hospital unit. A massive chylothorax was identified
      as the cause of the dyspnoea. Clinical and pathological findings were consistent
      with the diagnosis of lymphangiomyomatosis. The ligature of the thoracic duct as
      well as pleurodesis and the application of medroxyprogesterone were without any
      significant effect. Severe complications made further treatment in the intensive
      care unit imperative. Symptomatic treatment led only to a short remission. Five
      months after the outbreak of the disease the patient died from multiple organ
      failure.

PMID- 8991475
TI  - [Inspiratory pressure support via facial mask in acute respiratory
      insufficiency].
AB  - A patient in acute respiratory failure (Murray score 2.0) caused by pneumonia in
      the remaining lung 4 days after left-sided pneumonectomy was successfully treated
      with non-invasive pressure support by face mask. Non-invasive ventilation was
      chosen to keep the time of ventilating as short as possible, to achieve minimum
      pressure within the airways, and to retain natural defense and clearance
      mechanisms. Inspiratory pressure support was added to reduce increased work of
      breathing, improve ventilatory mechanics and gas exchange. Also, intrinsic PEEP
      was counterbalanced by external PEEP of 5 cmH2O to reduce work of breathing.
      Inspiratory pressure support of 15 cmH2O reduced respiratory rate to less than 30
      breaths/min, improved paO2 and reduced elevated paCO2 towards normal within 3
      hours. Duration of the non-invasive ventilation was 45 hours. There were no
      complications.

PMID- 8991476
TI  - [Report on the XXIII Neonatal and Infant Respiratory Symposium 10 to 15 March
      1996 in Vail, Colorado].

PMID- 8991477
TI  - Risk factors for fungemia in children infected with human immunodeficiency virus:
      a case-control study.
AB  - To define the risk factors related to the occurrence of fungemia in children
      infected with human immunodeficiency virus (HIV), we performed a matched case
      control study. During a 6-year period (1987-1993), fungemia developed in 22
      (6.3%) of 347 HIV-infected children observed at the Pediatric Branch of the
      National Cancer Institute. Each of these 22 cases was matched by age and gender
      with three controls. Multiple logistic regression indicated that the best
      predictor of fungemia in this population was the presence of a central venous
      catheter placed for > 90 days (P < .00001), followed by a group of risk factors
      composed of 10 independent variables adjusted for a CD4 cell count of <
      100/MicroL (P < .045). Those variables included treatment with more than three
      antibiotics, treatment with more than three parenteral antibiotics, > 30 days of
      antibiotic treatment, bacterial infections, > 30 days in the hospital,
      hypoalbuminemia, C3 (Centers for Disease Control and Prevention) classification
      of HIV infection, and malnourishment. We conclude that prolonged placement of
      central venous catheters is the most important risk factors for fungemia in HIV
      infected children and that the risk of fungemia is further influenced by
      antibacterial therapy, catheter manipulation, and host response.

PMID- 8991478
TI  - Glutaraldehyde as a fixative in bioprostheses and drug delivery matrices.
AB  - The use of glutaraldehyde as a fixative in bioprostheses and drug delivery
      matrices is reviewed. The chemistry of glutaraldehyde cross-linking and its
      effect on the biological performance of a number of bioprostheses such as tissue
      heart valves, vascular grafts, pericardial patches, tendon grafts and drug
      delivery matrices are examined.

PMID- 8991479
TI  - Effects of processing conditions and in vitro ageing on the physical properties
      of Biomer.
AB  - Biomer is generally processed by repeated deposition of layers by solution
      casting onto a preshaped former. The precise nature of this processing route may
      influence the mechanical response and surface properties of the finished article
      and, as a result, its subsequent in vivo behaviour. Here we have studied the
      influence of a range of processing parameter: the type of former, the initial
      concentration of the solution from which the layers are cast and the time
      interval between casting of successive layers. The subsequent variation of
      physico-chemical properties on vitro ageing in isotonic saline solution has also
      been considered and, in particular, the possibility of cross-linking during long
      term exposure.

PMID- 8991480
TI  - Evaluation of the effect of three surface treatments on the biocompatibility of
      316L stainless steel using human differentiated cells.
AB  - AISI 316L stainless steel (SS) is widely used in orthopaedic implantology,
      although biological complications may result from its insufficient mechanical and
      tribological properties. In order to improve the wear and corrosion resistance as
      well as the hardness of 316L SS, three surface treatments, derived from those
      applied in mechanical engineering industries, were investigated: (1) glow
      discharge nitrogen implantation, (2) carbon-doped stainless steel coating
      sputtering and (3) low temperature plasma nitriding. Surface characterization
      according to the different heat treatments showed that corrosion and wear
      resistance were strongly improved, especially by ion implantation or carbon-doped
      SS coating sputtering. In the same way, microhardness was significantly increased
      after the three treatments. The effect of such treatments on the biocompatibility
      of 316L SS was studied with human osteoblast and fibroblast cultures. Basic and
      specific features of the cells showed that ion-implanted and carbon-doped
      stainless steels were biocompatible, whereas dramatic cellular reactions were
      noted when contacted with nitrided stainless steel. A hypothesis is given to
      explain this observation but further experiments are needed to optimize the
      nitriding process. Nitrogen implantation and carbon-doped layer deposition could
      be efficient means for improving the physical properties of stainless steel
      without affecting its biocompatibility. Such surface treatments may have
      relevance for increasing the life time of 316L biomedical devices.

PMID- 8991481
TI  - Synthetic implant surfaces. 1. The formation and characterization of sol-gel
      titania films.
AB  - Sol-gel has been used to prepare thin titania films. We have investigated the
      effects of dip rate, sintering temperature and time on the chemical composition
      of the films, their physical structure and thickness, and adherence to a silica
      substrate. Our aim has been to produce films that mimic as closely as possible
      the natural oxide layer that is found on titanium. These films are to be used as
      substrates in an in vitro model of osseointegration.

PMID- 8991482
TI  - New aspects of the effect of size and size distribution on the setting parameters
      and mechanical properties of acrylic bone cements.
AB  - The effect of the size and the size distribution of poly(methyl methacrylate)
      (PMMA) beads on the classical kinetic parameters, peak temperature and setting
      time, for acrylic bone cement formulations prepared with PMMA particles in the
      range 10-60 microns of average diameter and a relatively wide size distribution
      is analysed. In addition, the combined effects of the concentration of the free
      radical initiator benzoyl peroxide and the activator N, N-dimethyl-4-toluidine
      for the different particle sizes are studied and compared with those commercially
      available formulations like CMW or Rostal. The results obtained indicated that
      the use of PMMA particles with average diameter of 50-60 microns, and a
      relatively wide size distribution (10-140 microns diameter), significantly
      changes the curing parameters (peak temperature and setting time) of the cement
      formulations in comparison with the classical behaviour of the commercial systems
      of CMW and Rostal, without any noticeable loss in the mechanical properties, such
      as tensile strength, elastic moduli, and compressive strength and plastic strain.

PMID- 8991483
TI  - Structural features of latex gloves in dental practice.
AB  - The aim of this study was to define from a morpho-structural point of view, using
      scanning electron microscopy, the features of various types of disposable latex
      gloves commonly used in Italian dental practice (Biogel D, Trend, Pagni, J&J,
      Latechnics, Pehasoft, Bantex). None of the brands examined was free from
      morphological flaws; however, while in some of these only slight depressions were
      found (Biogel D, Trend), in others (Latechnics, Bantex) there was a marked lack
      of homogeneity in the latex structure or real holes (Pehasoft). This study
      emphasizes the current difficulties faced by dentists in the search for safe
      working conditions.

PMID- 8991484
TI  - The effect of thermal treatment on sterility, molecular and mechanical properties
      of various polylactides. I. Poly(L-lactide).
AB  - Resorbable pins for the treatment of osteochondral defects produced by injection
      moulding from poly(L-lactide) were subjected to the action of heat at 105-150
      degrees C under a low moisture and low oxygen atmosphere for a predetermined
      time. Standard procedures were used to evaluate the sterility, mechanical
      properties, molecular weight, polydisperity and crystallinity of the heat-treated
      samples. All of the heat-treated samples were sterile after 2 h of exposure to
      heat. There was an 10% increase in the shearing strength of the samples treated
      thermally for up to 10 h. This was attributed to the increase in overall
      crystallinity and crystal dimensions in the samples which enhanced the
      propagation of cracks formed upon testing through areas of high ductility. There
      was, however, a 20-35% drop in flexural strength which might result from the
      decreased concentration of the amorphous regions in the heat-treated implants. A
      20% increase in molecular weight of the heat-treated implants was assigned to the
      transesterification process between the -OH and -COOH groups present initially in
      the polymer and/or formed due to chain scission upon exposure of the material to
      heat.

PMID- 8991485
TI  - Enhancement of the mechanical properties of polylactides by solid-state
      extrusion. I. Poly(D-lactide).
AB  - Resorbable rods with circular cross-section were produced from poly(D-lactide)
      with Mv = 160,000 by solid-state extrusion through a conical die. The effects of
      extrusion temperature and the draw ratio/rate in the solid state on the final
      mechanical properties and morphology of the rods were evaluated. While the rods
      produced from polylactides by routine injection-moulding have bending strengths
      in the range of 40-140 MPa and bending moduli in the range of 2-5 GPa, the solid
      state extrusion under the conditions applied led to rods with bending strengths
      at yield of up to 200 MPa and bending moduli of up to 9 GPa. Typically, for the
      highly oriented polymeric materials, the pins produced by the solid-state
      extrusion had highly fibrillated morphology.

PMID- 8991486
TI  - Addressing processing problems associated with plasma spraying of hydroxyapatite
      coatings.
AB  - Biomedical coatings generally have to satisfy specific requirements such as a
      high degree of crystallinity (for positive biological responses), good coating
      adhesion and optimal porosity. These are necessary to enhance biocompatibility,
      accelerate post-operative healing and improved fixation. Thermal spray processes
      have been frequently used to deposit functionally active biomedical coatings,
      such as hydroxyapatite (HA), onto prosthetic implants. The benefits of HA
      materials in coated implants have been widely acknowledged, but the occurrence of
      several poor performances has generated concerns over the consistency and
      reliability of thermally sprayed HA coatings. Recent investigations using HA
      coatings have shown that process related variability has significant influence on
      coating characteristics such as phase composition, structure and chemical
      composition and performance such as bioresorption, degradation and bone
      apposition. Variation in process parameters such as powder morphology can induce
      microstructural and mechanical inconsistencies that have an effect on the service
      performance of the coating. In order to reach some acceptable level of
      reliability, it may be necessary to control existing variability in commercially
      available HA feedstock. In addition, certain opposing factors severely constrain
      the means to achieve the necessary coating conditions via thermal spraying alone;
      therefore, creating the need to introduce other innovative or secondary treatment
      stages to attain the desired results. This paper highlights some of the problems
      associated with plasma spray coating of HA and suggests that tailoring the powder
      feedstock morphology and properties through suitable conditioning processes can
      aid the deposition efficiency and produce an acceptable coating structure.

PMID- 8991487
TI  - Improved oral absorption of L-365,260, a poorly soluble drug.
AB  - L-365,260, a specific and potent nonpeptide antagonist of the CCKB receptor, is
      under investigation for its potential utility in the treatment of anxiety and
      panic disorders. This drug has a very low aqueous solubility (< 2 micrograms mL
      1). When L-365,260 was given orally as a suspension in 0.5% methylcellulose (5 mg
      kg-1), the absorption was rapid but incomplete. The peak concentrations occurred
      in about 30-40 min, and the bioavailability was 8.6% for the dog and 13.6% for
      the rat. The poor bioavailability could be attributed to poor absorption or
      extensive first-pass metabolism. By comparing the drug concentrations in the
      systemic circulation during portal and femoral (or cephalic) vein infusion, the
      hepatic first-pass metabolism was estimated to be 0.30 for the rat and 0.14 for
      the dog, suggesting that first-pass metabolism is not the main reason for the low
      bioavailability of the drug in rats and dogs. The limited bioavailability is,
      therefore, more likely due to its poor absorption as a result of its poor aqueous
      solubility and slow dissolution rate. However, while the absorption was
      substantially improved when the drug was given orally as a solution in PEG 600
      solution, the bioavailability increased threefold to fourfold in rats and sixfold
      to sevenfold in dogs. Although the underlying mechanism for the improved
      absorption is unknown, PEG 600 may have exerted a cosolubilizing effect which
      enhances the dissolution rate of L-365,260 in the GI tract, resulting in better
      absorption. Kinetic analysis by a deconvolution technique revealed that PEG 600
      increased both the extent and rate of absorption. These results are consistent
      with the notion that absorption of L-365,260 is rate limited by its dissolution
      rate. The data from these animal studies provides valuable information in
      selecting the formulation for clinical trials.

PMID- 8991488
TI  - Pharmacokinetics and food interaction of MK-462 in healthy males.
AB  - A study was conducted to assess the safety, tolerability, and pharmacokinetics of
      single intravenous (IV) doses of 5-90 micrograms kg-1 of MK-462, and the effect
      of food on the pharmacokinetics of MK-462 administered orally to healthy males.
      Results of this study indicate that IV doses of MK-462 from 5 to 90 micrograms kg
      1 are well tolerated. The disposition kinetics of MK-462 were linear for IV doses
      up to and including 60 micrograms kg-1. The values of the plasma clearance (CL),
      steady-state volume of distribution (Vss), plasma terminal half-life (t1/2), and
      mean residence time in the body (MRT) of MK-462 averaged 1376 mL min-1, 140 L,
      1.8 h, and 1.7 h, respectively, and remained essentially constant over the dosage
      range of 10-60 micrograms kg-1 of IV MK-462. However, as the dose increased from
      60 to 90 micrograms kg-1, the mean value of the apparent CL decreased from 1376
      to 807 mL min-1. Thus, elimination of MK-462 was dose dependent in this dosage
      range. Based on the disposition decomposition analysis (DDA), it was shown that
      the Vss value of MK-462 remained essentially constant over the dosage range of 10
      90 micrograms kg-1 of IV MK-462. The following values of two dose-independent
      parameters were also calculated by using DDA: distribution clearance (CLd) = 2028
      mL min-1, and mean transit time in the peripheral tissues (MTTT) = 0.74 h. The
      mean values of AUC, Cmax, tmax, and apparent t1/2 of MK-462 in 12 subjects each
      receiving a 40 mg tablet of MK-462 without breakfast were 330 ng.h mL-1, 77 ng mL
      1, 1.6 h, and 1.8 h, respectively. Although administration of a standard
      breakfast prior to dosing increased the AUC value (by approximately 20%) of MK
      462 and delayed its absorption, there were no significant effects of the meal on
      the values of Cmax and apparent t1/2 of MK-462.

PMID- 8991489
TI  - Pharmacokinetics and toxicokinetics of an orally active tripeptide, IRI-695, in
      animals.
AB  - Pharmacokinetics and toxicokinetics of IRI-695, a tripeptide, were investigated
      in the rat, rabbit, dog, and monkey. Tissue distribution and excretion of
      [14C]IRI-695 were determined in the rat. Following a single intravenous (IV)
      injection, the elimination half-life (t1/2) of IRI-695 in the rabbit, dog, and
      monkey was similar (about 65 min) and approximately four times that in the rat
      (15 min). This difference in t1/2 can be attributed to about four times higher
      clearance of the drug in rats (11.2 mL min-1 kg-1). The volume of distribution
      (Vss) in these four species, 132-234 mL kg-1, suggested negligible preferential
      distribution of IRI-695 to body tissue. After a 5 mg kg-1 oral dose, the absolute
      bioavailability of IRI-695 was 2.0% in rats and 3.1% in dogs. However, systemic
      drug exposure in the dog was about five to 10 times that in the rat, which is
      related to the slower clearance of the peptide in the dog. Toxicokinetic studies
      in the rat and dog indicated linear kinetics and systemic exposure of IRI-695 up
      to 300 mg kg-1 d-1 oral doses throughout the 28 d toxicity study. Accumulation of
      the drug after the repeated oral dosing was negligible. After a single 0.10 mg kg
      1 [14C]IRI-695 IV injection in rats, almost all of the radioactivity administered
      was excreted in urine within 24 h postdose.

PMID- 8991490
TI  - The relative bioavailability of two marketed controlled release diltiazem dosage
      forms at steady state in healthy volunteers.
AB  - This study was conducted to determine the relative bioavailability of Dilacor XR
      capsules compared to Cardizem CD capsules at both low (180 mg d-1) and high (540
      mg d-1) dose levels. Trough and serial plasma samples were obtained and
      pharmacokinetic parameters were calculated from the steady state concentration
      time profiles. Mean steady state plasma diltiazem concentrations (AUCss(0-24)) of
      Dilacor XR were 19% and 26% lower than those of Cardizem CD for the 180 mg d-1
      and 540 mg d-1 dose levels, respectively. In addition, Dilacor XR had lower mean
      Cmax,ss, Tmax,ss, Cmin,ss, and trough values than Cardizem CD with percentage
      differences ranging from 17% to 29%. The variability (%CV) in the data from the
      Dilacor XR treatments was higher for each calculated pharmacokinetic parameter
      compared to the Cardizem CD treatments. The %CV for Dilacor XR ranged from 34% to
      104% while the %CV for Cardizem CD ranged from 21% to 49%. From these results, it
      may be concluded that Dilacor XR is not bioequivalent to Cardizem CD at steady
      state doses of 180 mg d-1 and 540 mg d-1.

PMID- 8991491
TI  - Influence of cimetidine coadministration on the pharmacokinetics of sotalol
      enantiomers in an anaesthetized rat model: evidence supporting active renal
      excretion of sotalol.
AB  - Sotalol (STL) is an amphoteric, chiral beta-adrenergic blocking drug useful in
      the treatment of both hypertension and ventricular arrhythmias. In the human and
      rat, STL enantiomers are predominantly cleared from the body by the kidney as
      intact drug. The renal clearance (Clr) of STL enantiomers substantially exceeds
      the glomerular filtration rate (GFR) in the human and rat. In this report, the
      hypothesis that STL enantiomers are excreted by an active renal transport system
      was investigated in the rat by coadministering racemic STL (10 mg kg-1) with
      cimetidine, an inhibitor of renal tubular secretion of organic cations. To
      compare the effects of short-term and sustained cimetidine exposure on STL
      enantiomer disposition, cimetidine was administered either as a single bolus (30
      mg kg-1, n = 7) immediately prior to the STL dose, or as a 30 mg kg-1 bolus plus
      a 50 mg kg-1 infusion over the 6 h study period (n = 7). Blood and urine samples
      were collected over 6 h, during which time anaesthesia was maintained via
      intraperitoneal administration of pentobarbital. Cimetidine bolus and cimetidine
      infusion reduced STL enantiomer Clr by 43 and 59%, respectively, compared with
      respective saline controls. Significant stereoselectivity was observed in the
      cimetidine infusion group: systemic clearance, Clr (R > S), and AUC (S > R),
      although the magnitude of stereoselectivity was less than 5%. This study supports
      the hypothesis that STL enantiomers are predominantly cleared from the rat via a
      renal cationic transport mechanism and that this system can be competitively
      inhibited by the presence of cimetidine.

PMID- 8991492
TI  - Platelet kinetics after transfusion.
AB  - A kinetics model is proposed for platelet disposition after transfusion of
      platelets. In this model, transfusion of platelets and production of endogenous
      platelets contribute to an increase in the number of platelets in patients, and
      the life span and age of each platelet contribute to a decrease. The time course
      of the number of platelets after transfusion of platelets is theoretically
      described by this model to be a straight line followed by a concave curve. When
      the platelets have a life span without any variation, a linear pattern is
      observed in spite of their different ages at the transfusion. This model with a
      constant life span was applied to three patients receiving platelet transfusion,
      and the model parameters were calculated by curve fitting the observed platelet
      levels to the model using the nonlinear least-squares method. As a result, the
      life span, distribution volume per body weight, and endogenous platelet level
      (averages for three patients) were calculated as 6.29 d, 0.137 L kg-1, and 1.40 x
      10(4) counts microL-1, respectively. The calculated platelet levels in individual
      patients were compared with the observed ones during the next transfusions, and
      the relative and absolute differences between calculated and observed values were
      2.0 +/- 15.3% and -0.075 +/- 0.443 x 10(4) counts microL-1 (mean +/- SD, 15
      observed points for three patients), respectively. These case studies suggest
      that the model could be clinically useful for individual platelet transfusion.

PMID- 8991493
TI  - Relative bioavailability of four clomipramine hydrochloride tablet products.
AB  - The relative bioavailability of clomipramine was determined in two single-blind,
      single-dose, randomized, crossover studies. In the first study, the relative
      bioavailability of the test product, 2 x 25 mg clomipramine hydrochloride tablets
      (Noristan Ltd.), with respect to the reference product, Anafranil 2 x 25 mg
      tablets (clomipramine HCl; Ciba-Geigy (Pty) Ltd.) was determined. In the second
      study, the relative bioavailability of the test product, 5 x 10 mg clomipramine
      hydrochloride tablets (Noristan Ltd.), with respect to the reference product,
      Anafranil 5 x 10 mg tablets (clomipramine HCl; Ciba-Geigy (Pty) Ltd.), was
      determined. The geometric mean values for the variable Cmax were 31.3 ng mL-1 for
      the reference and 31.6 ng mL-1 for the test product in study 1. The geometric
      mean values for the variable AUC were 736 ng h mL-1 and 753 ng h mL-1 for the
      reference and test, respectively. In study 2, the geometric mean Cmax values were
      25.8 ng mL-1 and 23.9 ng mL-1 for the reference and test respectively; the
      geometric mean AUC values were 569 ng h mL-1 and 547 ng h mL-1. The 90%
      confidence intervals for the 'test/reference' mean ratios of the plasma
      clomipramine pharmacokinetic variables Cmax and AUC(0-infinity) (as measures of
      the rate and extent of absorption of clomipramine, respectively) fall within the
      conventional bioequivalence range of 80-125% for both studies. The test products
      (clomipramine HCl) are therefore bioequivalent to the reference products
      (Anafranil) with respect to the rate and the extent of absorption of clomipramine
      in both 10 mg and 25 mg strengths.

PMID- 8991494
TI  - [Challenges in the educational objectives of preventive medicine and community
      health curriculum in undergraduate medical education].
AB  - In the world-wide context of the current innovative movements in medical
      education it is of importance of set up the appropriate educational objectives-
      general instructional objectives (GIO) and specific behavioral objectives (SBO)
      for the undergraduate medical curriculum for preventive medicine and community
      health. These educational objectives should be constantly evaluated and modified
      according to the curricular changes which regularly occur so as to maintain
      relevance. An example is the recent modification of GIOs and SBOs in the
      curriculum of the University of Occupational and Environmental Health. Each
      sentence of 7 GIOs and 35 SBOs was simplified, keeping the original meaning
      (former texts in JJPH 37: 241-246, 1990, initially adopted in 1988) as much as
      possible. Further analysis of the example was performed including the rationale
      of the 7 GIOs, the setting up and continued evaluation of the SBOs to meet the
      relevance. Based on this analysis, future challenges include elaborating the
      minimal expected competencies (described as GIOs and SBOs in full sentence) in
      the course of preventive medicine and community health such as seen in the
      "Objectives of the Qualifying Examinations" of the Medical Council of Canada.

PMID- 8991495
TI  - [A review of epidemiologic studies on the health effects of indoor environments].
AB  - Indoor bioaerosols (viruses, bacteria, dust mites, molds, etc.) have become the
      subject of discussion on indoor environments. A number of epidemiologic studies
      on the health effects of molds and home dampness, the latter being an important
      determinant of mold growth, have been conducted mainly in Europe and the United
      States. In this paper, a review of these epidemiologic studies is described.
      Questionnaires are used as the method of exposure assessment in most of the
      studies. The necessity for developing objective methods of dampness/mold exposure
      assessment has been expressed by some researchers. Respiratory symptoms,
      especially asthman attacks and wheezing for children, have been utilized in many
      investigations as a health effect index. Positive relationship between home
      dampness/mold and respiratory symptoms have been shown in numerous studies.
      Dampness and/or molds in dwellings may effect respiratory symptoms, but several
      problems for determining causal inference still remain: exposure assessment,
      temporal relationship, etc. While the differences in house structure and life
      style between Japan and Europe/U.S.A. should be considered, the health effects of
      home dampness and molds need to also be examined in Japan which is a country with
      high humidity levels.

PMID- 8991496
TI  - [Development of a functional fitness test for the elderly].
AB  - A test of functional fitness defined as physical capacity to independently
      perform daily functional activities was developed for aged persons. The
      functional fitness test was composed of four physical capacity evaluation tasks
      representing physical abilities necessary to perform main activities of daily
      living; viz. sitting and standing up test, zig-zag walking test, hand working
      test with pegboard for dexterity evaluation, and rope working test for self-care
      evaluation. The reliability and feasibility of the test were examined with 765
      aged persons living in the community. The distribution of measurement values in
      each item showed neither extreme skewness nor kurtosis. Retest reliabilities for
      each task were 0.857 to 0.942, but the second trial showed significantly reduced
      (p < 0.001) values than the first trial in test-retest. Significant relationships
      (r = 0.503 to 0.627) between measurement values in each items and chronological
      age were found in both male and female. Functional fitness test and physical
      fitness test scores were correlated 0.740. These results showed that the
      functional fitness test developed in the present study has a high reliability and
      feasibility to evaluate functional capacity of daily living in aged persons.

PMID- 8991497
TI  - [Relationship of 'sekentei' to utilization of health, social and nursing services
      by the elderly].
AB  - The purpose of this study was to determine if a relationship exists between
      'sekentei' and utilization of health, social and nursing services. 'Sekentei' is
      the level of a person's self-consciousness of others observing one's behavior and
      endeavoring to meet the perceived norms of behavior. A questionnaire assessing
      'sekentei' was developed and utilized in a survey with 1,294 persons responding
      to the questionnaires. The results of this study were as follows: (1) 'Sekentei'
      was related to the place of birth, former occupation and education of persons.
      (2) Respondents who had a higher 'sekentei' score showed a tendency to have a
      sense of resistance concerning the use of services. (3) There was a significant
      relationship between 'sekentei' and utilization of services. These results show
      the importance of considering individual consciousness of 'sekentei' and
      characteristics of a community to facilitate use of services and remove the
      stigma related to social services in a community.

PMID- 8991498
TI  - [Ventilatory threshold in Japanese--as the basis for exercise prescription for
      health promotion].
AB  - Oxygen consumption (VO2) at ventilatory threshold (VT) was measured in 610
      healthy Japanese with differing ages (305 men: 45.1 +/- 15.8 years; 305 women:
      44.3 +/- 16.0 years) to develop a scale for exercise prescription with the
      ultimate purpose of health promotion. Ramp exercise test using a bicycle
      ergometer was used as an exercise loading test. VT was determined using the
      breath by breath method. Standard aerobic capacity was determined according to
      age and sex using VT as the indicator. 1) VO2 at VT(Y) decreased with age (X),
      and closely approximated a single regression formula, Y = 22.4-0.16X (r = -0.626,
      p < 0.001) for men and Y = 18.1-0.10X (r = -0.578, p < 0.001) for women. 2) There
      was a sex difference in VT being significantly (p < 0.01) higher in men than in
      women. 3) The work rate (WR) at VT was also significantly higher in men. 4) There
      was no sex difference in heart rate (HR) at VT; 115 beats/min. in subjects in
      their 30 s, 110 beats/min. in those in their 40 s, 105 beats/min. in those in
      their 50 s, and 100 beats/min. in those in their 60 s. 5) Rating of perceived
      exertion (RPE) at VT was not influenced by age or sex differences, and was about
      13. 6) The minimum level of VT, at which daily living activities was possible was
      about 3 METs. 7) There was a significant positive correlation between mean number
      of steps per day and VT. VO2, HR and WR at VT decreased with age although there
      was no sex difference in HR, and there was no age or sex difference in RPE. These
      results suggest that health promoting exercise can be prescribed on the basis of
      HR which would be identical figures for men and women of the same age, and also
      by RPE specified as less than "somewhat hard".

PMID- 8991499
TI  - [Mortality of SMON patients in relation to their disabilities].
AB  - The relationship between mortality and disability, was studied in SMON patients,
      who had participated in the questionnaire survey in 1980, by following them for
      10 years through municipal resident registration information offices. Eighty
      deaths were observed among 409 subjects during the follow-up period. The effect
      of each disability on the mortality of SMON was estimated by applying the Cox
      proportional hazard model. The presence of severe gait disturbance and low levels
      of activities of daily living (ADL) were associated with significantly higher
      risk of death after adjustment for age and sex. The relative risk of visual
      disturbance was not significant after adjusting for age, sex and other kinds of
      disability. Those who complained of continuous dysesthesia at the time of the
      initial survey showed better prognosis than those without such dysesthesia. Among
      subjects who died during the follow-up period, those who had reported low levels
      of ADL at the time of the initial survey had a greater proportion of deaths
      attributable to heart failure and pneumonia than those who had reported high
      levels of ADL.

PMID- 8991500
TI  - [Follow-up study of obese pupils and their life styles in the lower grades of
      primary schools].
AB  - Physical examinations and a questionnaire survey of life style were carried out
      on all pupils (105 boys and 110 girls) at the first grade of primary school in
      Saigo town, Fuse village, Goka village, and Tsuma village of Shimane prefecture
      in 1992. In 1994, physical examinations and a questionnaire survey were again
      performed along with a newly-added blood examination on the same cohort. Parents
      of the pupils answered the questionnaire. The pupils who were included in both
      the first (in 1992) and the second (in 1994) examinations and surveys (89 boys
      and 101 girls, but 71 boys and 77 girls for blood examination) were subjects in
      this study to analyse the relationship between obesity and life style. The
      results showed (a) the proportional rates of obese boys and girls increased
      during the two years; (b) the obesity index of boys and girls in the third grades
      correlated with the obesity index of their mothers; (c) obese boys ate snacks
      frequently, had a higher speed in eating, and disliked physical exercise; and (d)
      the obesity index of boys and girls correlated with serum total cholesterol.
      These findings indicate that obesity occurs as early as the lower grades of
      primary schools and that it continues for at least two years.

PMID- 8991501
TI  - [Trends on results of health screening for residents in Y city, Osaka from 1986
      to 1993].

PMID- 8991502
TI  - Multiresidue determination of sulfonamide antibiotics in milk by short-column
      liquid chromatography coupled with electrospray ionization tandem mass
      spectrometry.
AB  - Liquid chromatography coupled to electrospray mass spectrometry and tandem mass
      spectrometry has been used for the determination and quantification of 21
      sulfonamides and two potentiators (ormethoprim, trimethoprim) in milk. Separation
      using high-performance liquid chromatography was achieved in less than 6 min for
      all compounds on a short (4.0 x 50 mm, 3 micron) reversed-phase column. After
      sample clean-up, time-scheduled single-ion monitoring (SIM) yielded detection of
      sulfonamides in milk from low ppb level to the ppt level. The strategy used to
      detect, confirm and quantify sulfonamides in milk samples was as follows: (a) pre
      screening (and cp3firmation) of target and non-target sulfonamides by precursor
      ion scan and/or multiple reaction monitoring experiments using generic product
      ions; (b) quantification of identified target compounds by monitoring their
      protonated molecule ions in a time-scheduled SIM experiment; (c) further
      confirmation, if necessary, by selected reaction monitoring using characteristic
      product ions.

PMID- 8991503
TI  - Matrix-assisted laser desorption/ionization mass spectrometry in milk science.
AB  - The protein content of several cow milks was investigated by matrix-assisted
      laser desorption/ionization (MALDI) mass spectrometry. In particular, milk from
      four different breeds of cow (Holstein Frisons, Brown Swiss, Jersey and Reggiana)
      at the same lactation stage and under the same feeding system were analysed and
      clear differences were found in their MALDI spectra. The various lactation stages
      were also investigated. A series of analyses were devoted to industrial milk
      treatment, by studying possible thermal damage occurring during milk
      pasteurization and sterilization.

PMID- 8991504
TI  - Tissue-specific regulation of sialyltransferase activities in the rat by
      corticosteroids in vivo.
AB  - In this study we have examined the effects of corticosteroids on both the total
      sialyltransferase (sialyl-T) activity and on two individual isozymes in neural,
      hepatic, and renal tissues using an in vivo model system. Rats were
      adrenalectomised to deplete their endogenous stores of steroid hormones, and some
      subsequently received steroid replacement with dexamethasone or aldosterone.
      Adrenalectomy resulted in a significant decrease in total neural sialyl-T
      activity when compared with sham-operated animals in the four brain regions
      examined, indicating that total sialyl-T activity is normally under positive
      corticosteroid control. The subsequent effects of exogenous corticosteroids
      exhibited regional specificity with the enzyme activities in the cortex,
      cerebellum, and brainstem being stimulated by both dexamethasone and aldosterone
      and enzyme activity in the hippocampus being stimulated by aldosterone alone. In
      general, the changes in total enzyme activity could be attributed to the alpha
      2,6 sialyl-T isozyme, although the changes in the cerebellum appeared to coincide
      with alpha 2,3 sialyl-T activity. In the liver, adrenalectomy resulted in an
      increase in enzyme activity which was not altered by administration of
      corticosteroids. There were no changes in total renal sialyl-T activity in any of
      the four experimental groups although certain changes were observed at the level
      of individual sialyl-T isozymes. These results demonstrate that sialyl-T activity
      in certain tissues is under the control of corticosteroids and that this is both
      a tissue-specific and region-specific effect.

PMID- 8991505
TI  - The glycans of soybean peroxidase.
AB  - Soybean hull peroxidase (SBP, E.C. 1.11.1.7), an anionic glycoprotein, was found
      to contain 18.2% carbohydrate with the average composition: 2 mol GlcNAc, 3.3 mol
      Man, 0.9 mol Fuc, and 0.7 mol Xyl. The oligosaccharides of SBP, after release
      with glycopeptidase A, were investigated by a combination of high pH anion
      exchange chromatography with pulsed amperometric detection, methylation analysis
      and matrix assisted laser desorption/ionization-time-of-flight mass spectrometry.
      The structure of the major oligosaccharide, accounting for 60 to 65% of the
      total, is Man alpha 1-->6(Man beta 1-->3)(Xyl beta 1-->2)Man beta 1-->4GlcNAc
      beta 1-->4(Fuc alpha 1-->3)GlcNAc. A further 20 to 25% of the released
      oligosaccharides belong to the (Xyl)xManm(Fuc)fGlcNAc2 (m = 2, 4, 5, 6; f = 0 or
      1, x = 0 or 1) family. The rest of the oligosaccharides were of the high-mannose
      type. Investigation of the six tryptic fractions containing carbohydrate revealed
      considerable heterogeneity in the N-linked oligosaccharides present in each
      fraction. The major glycan (4, Table III) was present in each fraction. Two of
      the fractions contained the major part of the high-mannose type glycans,
      ManmGlcNAc2 (m = 5-9), the major species being Man7GlcNAc2. The other four
      fractions contained mainly members of the (Xyl)xManm(Fuc)fGlcNAc2 (m = 2, 4, 5,
      6; f = 0 or 1; x = 0 or 1) family. Methylation analysis of the holo- and apo-SBP
      provide support for the structures proposed for the oligosaccharides as well as
      for the heterogeneity of the glycopeptide fractions.

PMID- 8991506
TI  - Regarding galactofuranose-containing glycoconjugates.

PMID- 8991507
TI  - Pathways of glycosphingolipid biosynthesis in SW13 cells in the presence and
      absence of vimentin intermediate filaments.
AB  - We reported previously that the incorporation of sugars into glycosphingolipids
      (GSL) is diminished in SW13 cells that lack a vimentin intermediate filament (IF)
      network (vim-) compared to vim+ cells. To further analyze the nature of this
      abnormality, we double-labeled cells with 3H-serine and 14C-sugars. There was no
      difference between vim+ and vim- cells in the incorporation of serine into GSL,
      although the usual difference in sugar incorporation was observed. This indicated
      that the defect in vim- cells was not in the incorporation of sugars into
      ceramide synthesized de novo by acylation of sphinganine (pathway 1). Sugars can
      also be incorporated into ceramide synthesized from sphingosine that is derived
      from catabolism of sphingolipids (pathway 2), and into GSL that recycle through
      the Golgi apparatus from endosomes (pathway 3). The amount of galactose and
      glucosamine incorporated into GSL in these three pathways was analyzed by the use
      of two inhibitors of sphingolipid biosynthesis. beta-Chloroalanine inhibits the
      de novo synthesis of sphinganine (pathway 1), and fumonisin B1 inhibits the
      acylation of sphinganine and sphingosine (pathways 1 and 2). We were surprised to
      observe that in both vim+ and vim- cells only 20-40% of sugar incorporation into
      GSL took place in pathway 1, and 60-80% of sugar incorporation took place in the
      recycling pathways. Moreover, in contrast to larger GSL, GlcCer was not
      synthesized in pathway 3. Our observations indicate that vimentin IF facilitate
      the recycling of GSL and sphingosine, and that the differences between vim+ and
      vim- cells are predominantly in pathways 2 and 3. Furthermore, although it is
      generally believed that virtually all GSL are synthesized in the de novo pathway,
      these data indicate that the recycling pathways predominate in the incorporation
      of sugars into GSL in SW13 cells.

PMID- 8991508
TI  - Mouse submandibular gland salivary apomucin contains repeated N-glycosylation
      sites.
AB  - A cDNA clone encoding mouse submandibular gland salivary mucin apoprotein was
      isolated and characterized. The mucin cDNA encodes a protein of 273 amino acids
      with a calculated molecular weight of 29,606. This apomucin is approximately 60%
      Thr, Ser, and Pro, and has a pI of 11.25. In addition to the signal sequence, the
      apomucin can be divided into four structural domains. The first of these contains
      over 30% Thr, Ser, and Pro, but only a few probable O-glycosylation sites. The
      second domain contains 10 repeats, each 9 or 13 amino acids in length, with Thr
      representing more than 50% of the amino acids, while Ser accounts for only 2%.
      Each repeat begins with a putative N-glycosylation site; hence this domain likely
      contains both N- and O-linked oligosaccharides. The third domain lacks a repeat
      motif, but is rich in both Thr and Ser, and therefore is potentially highly O
      glycosylated. The final domain is composed mainly of basic and non-polar amino
      acids and does not contain Cys. This mucin shows considerable homology with the
      rat submandibular salivary mucin, but little overall homology with other mucins.
      In situ hybridization verifies that the mucin transcript is localized primarily
      in the acinar cells of the submandibular gland.

PMID- 8991509
TI  - Enzymatic sulfation of galactose residue of keratan sulfate by chondroitin 6
      sulfotransferase.
AB  - We have previously found that the purified chondroitin 6-sulfotransferase (C6ST),
      which transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to
      position 6 of N-acetylgalactosamine in chondroitin, catalyzed the sulfation of
      keratan sulfate, and that both the C6ST activity and the keratan sulfate
      sulfotransferase (KSST) activity were expressed in COS-7 cells when C6ST cDNA was
      transfected. In this report we describe some properties of the KSST activity
      contained in the purified C6ST, and characterize the sulfated products formed
      from keratan sulfate and partially desulfated keratan sulfate. Optimal pH,
      requirement for cationic activators, and Km value for PAPS of the KSST activity
      were very similar to those of the C6ST activity. 35S-Labeled glycosaminoglycans
      formed from keratan sulfate and partially desulfated keratan sulfate were N
      deacetylated by treatment with hydrazine/hydrazine sulfate and then cleaved with
      HNO2 at pH 4, and the resulting products were reduced with NaB3H4. Analysis of
      the degradation products with paper chromatography and high performance liquid
      chromatography provided evidence that C6ST transferred sulfate to position 6 of
      galactose residue which was glycosidically linked to N-acetylglucosamine 6
      sulfate residue or to N-acetylglucosamine residue. Northern blot analysis using
      poly (A)+ RNA from 12-d-old chick embryos indicated that the message of C6ST was
      expressed not only in the cartilage but also in the cornea in which keratan
      sulfate is actively synthesized.

PMID- 8991510
TI  - Sea urchin egg receptor for sperm: the oligosaccharide chains stabilize sperm
      binding.
AB  - Sulfated O-linked oligosaccharides from the sea urchin egg receptor have been
      shown to bind to acrosome-reacted sperm and to inhibit fertilization in a
      competitive bioassay. However, the inhibitory activity of these isolated chains
      was much lower than that of a recombinant protein representing a portion of the
      extracellular domain of the receptor. Because the isolated oligosaccharides
      lacked the potential polyvalency that they might have when linked to the
      polypeptide backbone, in the current study we asked if their inhibitory activity
      could be increased by chemically coupling them to a protein to form a
      neoglycoprotein. Using a recombinant fragment of the receptor we could not detect
      an oligosaccharide dependent increase in inhibitory activity with this
      neoglycoprotein, probably because of the much higher inhibitory activity of the
      polypeptide backbone. Therefore, we examined the activity of the oligosaccharides
      coupled to a protein lacking the ability to inhibit fertilization, namely, bovine
      serum albumin. A marked increase in the inhibitory activity of the
      oligosaccharides was observed with this neoglycoprotein. Finally, because
      inhibition by the oligosaccharides and the polypeptide was measured in an end
      point assay, namely, inhibition of fertilization, we sought a more direct,
      kinetically sensitive way to measure their properties. Accordingly, an assay was
      devised (R.L. Stears and W.J. Lennarz, unpublished observations) involving
      measurement of sperm binding to beads that was dependent on the presence of the
      receptor or its components. This assay revealed that sperm binding to beads via
      the recombinant protein peaked at 10 sec and then declined. In contrast, binding
      mediated by neoglycosylated recombinant protein reached a plateau. Thus, binding
      of sperm to the oligosaccharides resulted in a more stable interaction than that
      observed in binding to the polypeptide backbone.

PMID- 8991511
TI  - Synthesis of a tetravalent sialyl Lewis x glycan, a high-affinity inhibitor of L
      selectin-mediated lymphocyte binding to endothelium.
AB  - Kidney transplant rejection is an inflammatory process characterized by
      lymphocyte infiltration. Our earlier observations have shown that peritubular
      capillary endothelium (PTCE) is the site of lymphocyte entry into the rejecting
      renal allograft. During rejection, PTCE begins to express sialyl Lewis x de novo,
      and binds lymphocytes by a mechanism largely dependent on L-selectin. Hence,
      inhibiting the lymphocyte-endothelial interaction with oligosaccharide ligands of
      L-selectin offers an attractive possibility to prevent the inflammation and
      rejection. Here, we report enzyme-assisted synthesis of N-acetyllactosamine-based
      tetra-, deca-, and docosameric saccharides carrying one, two or four distally
      located sialyl Lewis x groups [Neu-NAc alpha 2-3Gal beta 1-4(Fuc alpha 1
      3)GlcNAc] (sLex), respectively. When tested for their ability to inhibit
      lymphocyte-endothelial interaction during rat kidney transplant rejection, all
      sLex-saccharides were inhibitors in the Stamper-Woodruff binding assays; the
      analogues lacking fucose showed no inhibitory potency. The tetravalent sLex
      glycan proved to be a high-affinity adhesion inhibitor with an IC50 < 50 nM.
      While less powerful than the tetravalent glycan, also the divalent sLex
      saccharide was a much better inhibitor than the monovalent glycan. Hence,
      increasing multivalency and, possibly, increasing chain length of the
      polylactosamine backbone, enhances the inhibitory potency of sLex bearing glycans
      in the lymphocyte-endothelial adhesion assay. This suggests that L-selectin
      behaves as a "functional oligomer" on lymphocyte surfaces.

PMID- 8991512
TI  - Human melanoma and Chinese hamster ovary cells galactosylate n-alkyl-beta
      glucosides using UDP gal:GlcNAc beta 1,4 galactosyltransferase.
AB  - We previously showed that human melanoma, CHO and other cells can convert beta
      xylosides into structural analogs of ganglioside GM3. We have investigated
      several potential acceptors including a series of n-alkyl-beta-D-glucosides (n =
      6-9). All were labeled with 3H-galactose when incubated with human melanoma
      cells. Octyl-beta-D-glucoside (Glc beta Octyl) was the best acceptor, whereas
      neither octyl-alpha-D-glucoside nor N-octanoyl-methylglucamine (MEGA 8) were
      labeled. Analysis of the products by a combination of chromatographic methods and
      specific enzyme digestions showed that the acceptors first received a single Gal
      beta 1,4 residue followed by an alpha 2,3 linked sialic acid. Synthesis of these
      products did not affect cell viability, adherence, protein biosynthesis, or
      incorporation of radiolabeled precursors into glycoprotein, glycolipid or
      proteoglycans. To determine which beta 1,4 galactosyl transferase synthesized Gal
      beta 1,4Glc beta Octyl, we analyzed similar incubations using CHO cells and a
      mutant CHO line (CHO 761) which lacks GAG-core specific beta 1,4
      galactosyltransferase. The mutant cells showed the same level of incorporation as
      the control, eliminating this enzyme as a candidate. Thermal inactivation
      kinetics using melanoma cell microsomes and rat liver Golgi to galactosylate Glc
      beta Octyl showed the same half-life as UDP-Gal:GlcNAc beta 1,4
      galactosyltransferase, whereas LacCer synthase was inactivated at a much faster
      rate. We show that Glc beta Octyl is a substrate for purified bovine milk UDP
      Gal:GlcNAc beta 1,4 galactosyltransferase. Furthermore, the galactosylation of
      Glc beta Octyl by CHO cell microsomes can be competitively inhibited by GlcNAc or
      GlcNAc beta MU. These results indicate that UDP-Gal:GlcNAc beta 1,4
      galactosyltransferase is the enzyme used for the synthesis of the alkyl
      lactosides when cells or rat liver Golgi are incubated with alkyl beta
      glucosides.

PMID- 8991513
TI  - Molecular and phenotypic analysis of the S. cerevisiae MNN10 gene identifies a
      family of related glycosyltransferases.
AB  - The Saccharomyces cerevisiae mnn10 mutant is defective in the synthesis of N
      linked oligosaccharides (Ballou et al., 1989). This mutation has no effect on O
      linked sugars, but results in the accumulation of glycoproteins that contain
      severely truncated N-linked outer-chain oligosaccharides. We have cloned the
      MNN10 gene by complementation of the hygromycin B sensitivity conferred by the
      mutant phenotype. Sequence analysis predicts that Mnn10p is a 46.7 kDa type II
      membrane protein with structural features characteristic of a
      glycosyltransferase. Subcellular fractionation data indicate that most of the
      Mnn10 protein cofractionates with Golgi markers and away from markers for the
      endoplasmic reticulum (ER), suggesting Mnn10p is localized to the Golgi complex.
      A comparison of the Mnn10 protein sequence to proteins in the two different
      databases identified five proteins that are homologous to Mnn10p, including a
      well characterized Schizosaccharomyces pombe alpha 1,2 galactosyltransferase that
      resides in the Golgi complex. Taken together, these results suggest that MNN10
      encodes a novel Golgi-localized mannosyltransferase contained in this previously
      unrecognized family of related sugar transferases.

PMID- 8991514
TI  - Exoglycosidase purity and linkage specificity: assessment using oligosaccharide
      substrates and high-pH anion-exchange chromatography with pulsed amperometric
      detection.
AB  - Simplified HPLC protocols to determine the activity and linkage specificity and
      to detect the most commonly-encountered contaminants in available exoglycosidase
      preparations (Jacob and Scudder, Methods Enzymol., 230, 280-300, 1994) were
      developed. Monosaccharides and oligosaccharides were analyzed in a single
      chromatographic step using high-pH anion-exchange chromatography with pulsed
      amperometric detection. All analyses were performed with underivatized
      oligosaccharide substrates and by direct injection of unprocessed, diluted enzyme
      digests into the chromatograph. The sialidase from Newcastle disease virus was
      found to release both alpha (2-->3)- and alpha (2-->6)-linked Neu5Ac from a
      triantennary, lactosamine-type oligosaccharide. The activity of alpha
      galactosidase from green coffee beans was assayed using Gal alpha(1-->3)[Fuc
      alpha(1ar2)]Gal by detection of Gal and Fuc alpha(1-->3)Gal. The linkage
      specificities of beta-galactosidases from Streptococcus pneumoniae and bovine
      testis were assessed using Gal beta(1-->3 or 4)GlcNAc beta(1-->3)beta(1-->4)Glc
      as substrates. Contaminating beta-N-acetylhexosaminidase activity in the beta
      galactosidase preparation was assayed using an agalactobiantennary
      oligosaccharide. The alpha(1-->3 or 4) linkage specificity of fucosidase III from
      almond meal was confirmed (Scudder et al., J. Biol. Chem. 265, 16472-16477, 1990)
      by its inactivity against a biantennary oligosaccharide with all Fuc residues
      linked alpha(1-->6). An alpha-fucosidase from chicken liver was found to cleave
      alpha(1-->2,3 or 6)-linked Fuc residues from oligosaccharides. The activity of
      jack bean (Canavalia ensiformis) alpha-mannosidase was assayed with a relatively
      resistant substrate, Man alpha(1-->3)- Man beta(1-->4)GlcNAc. A GlcNAc beta(1-
      >4)-terminated triantennary oligosaccharide was used to assay for contaminating
      beta-N-acetylhexosaminidase activity in alpha-mannosidase preparations and to
      determine the linkage and branch specificity of beta-N-acetylhexosaminidase at
      different enzyme concentrations.

PMID- 8991515
TI  - Gastrointestinal surgery for severe obesity. NIH consensus development
      conference, March 25-7,1991.

PMID- 8991516
TI  - Large scale preparation of PA-oligosaccharides from glycoproteins using an
      improved extraction method.

PMID- 8991517
TI  - [Current concepts in sepsis].

PMID- 8991518
TI  - [Scheduled reinterventions in the treatment of acute peritonitis].
AB  - This is a clinical series of 83 cases, admitted in the Surgical Department of
      Fundeni Hospital between 1988-1996 of severe acute peritonitis in which scheduled
      reoperations (at least one planned reoperation at 24-48 hours after the first
      operation) were performed. The main criteria for scheduled reoperations were;
      unresolved source of contamination, acute peritonitis older than 48 hours and the
      presence of multiple system organ failures. 63 cases (76%) were postoperative
      peritonitis. 203 planned reoperations were performed (minimum: 1, maximum: 10,
      mean: 2,4 reoperations per patient). In 12 cases (14,4%) a laparotomy "on demand"
      was necessary after the scheduled reoperations were stopped. The source of
      peritonitis was resolved in 61 cases (73,5%) and unresolved in 22 cases (26,5%).
      In 9 cases (10%) specific complications of the method (hemorrhages, fistulas)
      were encountered. The global mortality was 65,06%, with 55,73% mortality when the
      source of peritonitis was resolved and 90,9% mortality when the source was not
      resolved. CONCLUSION: scheduled reoperations have to be reserved for the most
      severe cases of acute peritonitis in which the mortality after the "classical"
      methods of treatment is extremely high.

PMID- 8991519
TI  - [The evolutional characteristics and therapeutic options in primary suppurative
      pancreatitis].

PMID- 8991521
TI  - [Laparoscopic appendectomy in obese patients. A comparative study with open
      appendectomy].
AB  - The aim of this study is to show the advantages of laparoscopic versus classic
      appendectomy in obese patients. The trial includes 32 obese patients which
      underwent laparoscopic surgery for appendicitis in our clinic, compared to a
      similar trial of patients with open surgery. In both o trials we followed-up the
      operating time, postoperative pain, hospitalization and social and professional
      reintegration. We noticed that in laparoscopic appendicectomy patients
      postoperative pain and hospitalization are reduced, the bowel transit restants
      rapidly and spontaneously, there are no wound complications and patients recover
      faster. The disadvantages consisted in longer operative time and higher cost of
      the laparoscopic operation versus classic appendectomy.

PMID- 8991520
TI  - [Surgical injuries to the main bile ducts and their sequellae in "open"
      biliogastroduodenal surgery].
AB  - There are studied 53 patients (1984-1995) with surgical injuries (and/or sequels)
      of the main biliary duct (MBD) produced during biliary and gastro-duodenal "open"
      interventions. The patients are classified in the following categories: I) 7
      (13%) with the ductal accident diagnosed and repaired in the time of the same
      operation. Produced in our clinic (0.13% of the total predisposing operations),
      all patients healed and there was not postoperative mortality. 2) 46 (87%)
      patients admitted from others surgical units: a) 17 with an immediate or
      precocious diagnosis of the surgical MBD trauma and b) 29 with late diagnosis
      having various MBD strictures (6 of them have had corrective interventions which
      became ineffective in time). All the patients have had overadded around 3 risk
      factors. The principles applied in the treatment of this iatrogenic lesions were:
      # If the surgical injury was recognised during the causal operation--immediate
      repair: various ductal sutures or anastomosis with stent support maintained
      approximately 6-9 months. # The accident was discovered soon postoperatively: the
      remedial operation was postponed for a second time, after the surgical treatment
      of the evident complications (jaundice, angiocolitis, choleperitoneum, fistulas,
      etc). # The late diagnosed strictures of the MBD (without other local septic
      complications) benefited particularly by bilio-jejunal derivations (21 patients-
      72% from 29). The postoperative morbidity and lethality: 9 patients (19,5%/46),
      the main cause being different septic complications. 34 patients (64%/53), which
      we can followed, were alive between 2 and 10 years postoperatively. The best
      treatment of the surgical injuries of the MBD during the different biliary or
      gastroduodenal operations (practiced "a ciel ouvert") is their avoidance.

PMID- 8991522
TI  - [Obturation with an elastic balloon--the authors' procedure for the conservative
      treatment of external postoperative digestive fistulae].
AB  - A personal method for the conservative treatment of the postsurgical external
      digestive fistulas by means of obturation with an elastic balloon of adjustable
      pressure, used in Surgical Clinic I Craiova in the past 12 years is presented.
      Initially conceived as an elective method for the treatment of the fistulas
      exposed in evisceration, the procedure was later applied as a unique method or in
      association with other conservative procedure in almost all types of fistulas.
      122 patients have been treated by means of our method (3 esophageal, 65 gastro
      duodenal and gastro-intestinal, 27 intestinal and 27 colo-rectal fistulas), in 53
      cases a unique method and in 69 cases as a therapeutically sequences within the
      conservative treatment of the fistulas. RESULTS: 115 patients (94.2%) have had a
      fair evolution; we have registered 7 death, which represent a mortality rate of
      5.93%. CONCLUSIONS: Our method offers the following advantages: it considerably
      reduces the losses of digestive liquids through the fistula; it allows early
      resumption of normal nourishment; it allows early mobilization of the patients;
      it prevents the occurrence of new fistulas which are caused by decubitus lesions;
      it is a simple and economic method, which can be applied in any surgical
      department.

PMID- 8991523
TI  - [A case of abdominal pregnancy--a case report].
AB  - Rare anatomical variety, the ectopic abdominal gestation involve a high maternal
      and foetal risk. On report an abdominal gestation in the 2nd quarter of evolution
      at a 42 yrs. age of a female with multiple uterine leiomyomas, the diagnosis
      being establish by ultrasonography. The attitude in the same cases is decided by
      the foetal viability: if the foetus is in a life, the pregnant women is
      hospitalised and followed each day; if the foetus is dead, there are indication
      of surgery, the major problem being represented by the total or partial removed
      of the placenta.

PMID- 8991524
TI  - [The thermodynamic direction of biological evolution. The model and the reality].
AB  - A macrothermodynamic model of evolution of the supramolecular structures and
      chemical composition of living objects during ontogenesis and at long-term stages
      of general biological evolution is presented. A study of quasiclosed
      (thermodynamically and kinetically) systems, phases of the biomass supramolecular
      structures, enables a conclusion on the thermodynamic direction of biological
      evolution to be made. In correspondence with the second principle, this direction
      leads to variations in the chemical composition and structure of the living
      systems during their development. Indirect and direct evidence of the trend to a
      minimal Gibbs specific function of formation of the supramolecular structures in
      animal tissues during ontogenesis are presented. The conclusion that
      thermodynamics is the "driving force" of evolution of the biological world is
      confirmed.

PMID- 8991525
TI  - [A serum-free medium that preserves the normal morphology and high protein
      synthesis level in hepatocytes in vitro].
AB  - In a culture of rat hepatocytes, kept in a serum-free medium 199, the number of
      attached cells was decreased and a monolayer was not formed within 24 h. Soon
      after the cells were attached to collagen, the intensity of protein synthesis in
      the serum-free medium was decreased due to the smaller number of cells in the
      culture and was calculated per cell. The properties of cultures, i.e., the number
      and shape of cells, external appearance of the culture, and intensity of protein
      synthesis, were similar in a serum-containing medium and in the serum-free medium
      199 complemented with 0.2 mg/ml albumin and 5 micrograms/ml insulin. A monolayer
      typical for the medium with serum was formed in the medium with albumin and
      insulin within approximately 20 h after attachment of the hepatocytes to the
      substrate.

PMID- 8991526
TI  - [The structure of the skin of the external auditory canal and the antiviral
      activity of the cerumen in carnivorous mammals].
AB  - The structure of the meatus acusticus externus skin was studied in the sable,
      mink, and European polecat with a parallel estimation of antiherpetic activity of
      the cerumen. Morphologically, these species differ in the degree of fat cellulose
      development, vascularization, and association with the lymphoid tissue.
      Lymphocytes are present both in the tissue and along the skin gland ducts and
      hair follicles up to the external surface only in the sable. The cerumen samples
      have antiviral activity also in the sable alone. The relationship between
      physiological properties of the mammalian cerumen and morphogenetic features is
      discussed.

PMID- 8991527
TI  - [The concept of medical entomology: the determination of the effect of arthropods
      on human health].
AB  - A new concept of medical entomology is proposed, according to which this
      discipline should comprehensively study the effects of arthropods on human health
      and possible control of these effects. Thus, the tasks of medical entomology are
      markedly widened to embrace cognitively and practically important problems, which
      have been neglected. This approach does not negate the accepted understanding of
      medical entomology but includes it as an essential component.

PMID- 8991528
TI  - [An EPR study of the joint action of sodium nitrite and whole-body irradiation on
      animal tissues].
AB  - Changes in metabolic paramagnetic centers of the liver, kidney, spleen, brain and
      heart tissues, and blood after sodium nitrite intraperitoneal administration
      irradiation, or combined action of sodium nitrite and irradiation on mice, were
      studied using the EPR method. It was shown that irradiation of mice after sodium
      nitrite administration enhanced the effects induced by sodium nitrite alone: the
      levels of nitrosyl complexes Heme-NO in the tissues, cytochrome P-450 inhibition,
      and MetHb were higher.

PMID- 8991529
TI  - [Radionuclides in the benthofauna in the region of the location of the
      Komsomolets atomic submarine (the Norwegian Sea)].
AB  - Analysis of the content of radionuclides 137Cs and 90Sr in the benthofauna was
      carried out in the region of location of the nuclear submarine Komsomolets
      according to the materials of the 33rd voyage of RV Akademik Mstislav Keldysh
      (1994). No significant excess of the technogenic activity over the natural
      radioactivity was found in all ecological (trophic) groups of bottom animals. At
      the same time the content of 90Sr in the fauna of stations closer to the
      submarine was higher than at more remote stations.

PMID- 8991530
TI  - [Ecology and genetics: at the sources of synthesis].
AB  - In the 1920s V. V. Stanchinskii undertook an attempt at evolutionary synthesis on
      the basis of darwinism, new taxonomy, generalizations of population genetics of
      S. S. Chetverikov's school, the concept of Linnean species of N. I. Vavilov,
      ecological-genetic studies of the school of N. I. Vavilov, and data on
      biocenology. An original evolutionary-ecological concept was developed by V. V.
      Stanchinskii on this basis.

PMID- 8991531
TI  - [Electron microscopic study of migrating keratinocyte colonies].
AB  - Structural investigation of human migrating keratinocyte colonies in culture
      demonstrated cell heterogeneity in colony regions. The leading edge of the colony
      is surrounded by several layers of highly differentiated cells. The basal cells
      in the middle and front regions interplay with the help of long processes and
      form lamellipodia along the direction of the colony migration. Formation of the
      lamellipodia may be the driving force of migration. The suprabasal highly
      differentiated cells are elongated and flattened and form numerous desmosomes.
      Preserved cell contacts provide for movement of the colony as a united epithelium
      layer. Studies of migration of epidermal keratinocyte colonies bring light to
      understanding cell mechanisms of wound epithelialization and morphogenetic
      processes.

PMID- 8991532
TI  - [Modification of the mutagenic effects of gamma radiation by heavy metal salts].
AB  - The effect of K2Cr2O7 and (CH3COO)2Pb on the mutagenic activity of gamma rays was
      studied by a micronucleus test in mouse bone marrow polychromatocytes. Acute and
      chronic combined actions of the two factors were investigated. Chromium ions (VI)
      enhanced mutagenic effects of gamma rays in both acute and chronic experiments.
      In the acute experiments lead ions (II) below 15 mg/kg body weight decreased the
      number of gamma-ray-induced micronuclei, while higher doses increased it. Chronic
      combined action of lead ions (III) and gamma rays inhibited mutagenic activity of
      radiation.

PMID- 8991533
TI  - [The effect of long-term UV radiation exposure on the skin autonomous microflora
      and on body nonspecific resistance].
AB  - Hairless mice of strain HRS were exposed to vertical UV-B-irradiation (280-320
      nm) at daily doses of 1 or 2 kJ/m2 (biologically effective doses 200 and 400
      J/m2) five days a week for 13 and 6 weeks. As the length of exposure increased,
      the abundance of automicroflora of the dorsal skin first decreased, then exceeded
      the control value, was normalized, and remained at the normal level until the end
      of the experiment. The rates of effect appearance and disappearance, just as its
      amplitude, increased with the daily doses. No changes were found in resistance to
      staphylococcal alpha-toxin after its post-irradiation intraperitoneal injection.

PMID- 8991534
TI  - [Changes in the surface architectonics of erythrocytes under the influence of the
      synthetic antioxidant fenozan-1].
AB  - Scanning electron microscopy revealed changes in erythrocyte morphology induced
      by the synthetic antioxidant phenozan-1. Phenozan-1 at 10(-7)-10(-5) M acts as an
      echinocytogen. This effect of the antioxidant is, probably, due to its
      distribution in the external monolayer of the erythrocyte membrane and associated
      structural changes.

PMID- 8991535
TI  - Parvoviruses and bone marrow failure.
AB  - Parvovirus B19, the only known human pathogenic parvovirus, is highly tropic to
      human bone marrow and replicates only in erythroid progenitor cells. The basis of
      this erythroid tropism is the tissue distribution of the B19 cellular receptor,
      globoside (blood group P antigen). In individuals with underlying hemolytic
      disorders, infection with parvovirus B19 is the primary cause of transient
      aplastic crisis. In immunocompromised patients, persistent B19 infection may
      develop that manifests as pure red cell aplasia and chronic anemia. B19 infection
      in utero can result in fetal death, hydrops fetalis or congenital anemia.
      Diagnosis is based on examination of the bone marrow and B19 virological studies.
      Treatment of persistent infection with immunoglobulin leads to a rapid, marked
      resolution of the anemia.

PMID- 8991536
TI  - Interleukin 1 trials in cancer patients: a review of the toxicity, antitumor and
      hematopoietic effects.
AB  - Clinical trials of interleukin 1 alpha (IL-1 alpha) and IL-1 beta have been
      completed that assess the toxicities of these cytokines as well as their
      hematopoietic and antitumor effects. Both forms of IL-1 recognize the same cell
      surface receptors and have similar toxicities and similar biological activities.
      Toxicities including fever, flu-like symptoms and dose-limiting hypotension can
      be severe yet manageable, and IL-1 can be given safely to human cancer patients.
      Most toxicities and biological effects appear to be dose-related. IL-1 alone has
      little antitumor activity against melanoma, renal cell carcinomas or other
      malignancies. The hematopoietic effects, including megakaryocytopoietic effects,
      are modest and are probably not worth the toxicity necessary to achieve them.
      However, IL-1 seems to endow certain progenitor cells with responsiveness to
      other hematopoietic cytokines including colony-stimulating factors and IL-3. One
      potential application of IL-1 is to help expand bone marrow ex vivo following
      stem cell harvest, which could allow further chemotherapy dose escalations in
      chemotherapy-sensitive tumors.

PMID- 8991537
TI  - Cytokines and viral anti-immune genes.
AB  - Cytokines, the pleomorphic and pleiotropic director proteins of an increasingly
      defined diversity of differentiation and growth, are potent modulators of immune
      function and homeostasis. The antiviral and immunostimulatory actions of
      cytokines, like the interferons, have also been recognized for many years. In
      more recent developments, virus genomes were discovered in 1990 to contain anti
      immune genes that control the synthesis of host cell proteins that disarm immune
      defenses. Many of the virus anti-immune genes are directed against cytokines.
      Recent discoveries of cytokine homologs and cytokine receptor homologs, and other
      viral gene products that disarm host immune defenses, provide a molecular basis
      for improved understanding of virus diseases and new targets for development of
      innovative therapeutic approaches against viral, cancer and perhaps a number of
      other diseases.

PMID- 8991538
TI  - Peripheral blood progenitor cell transplantation: a replacement for marrow auto-
      or allografts.
AB  - Circulating hematopoietic progenitor cells include pluripotent stem cells
      expressing indefinite self-renewal capacity and, therefore, can be used for
      restoring hematopoiesis following myeloablative treatment. A transient shifting
      of progenitor cells from extravascular sites into the circulation by chemopriming
      and/or cytokine treatment enables the collection by apheresis of a sufficient
      number of progenitor cells to guarantee engraftment. The addition of new
      cytokines (e.g., thrombopoietin) and large volume apheresis will increase
      peripheral blood progenitor cell (PBPC) procurement efficiency, whereas the risk
      of concurrently mobilizing clonogenic tumor cells in patients with solid tumors
      and hematologic malignancies remains to be carefully evaluated. As compared with
      bone marrow (BM) progenitor cells, the use of PBPCs significantly shortens the
      recovery of WBC and platelets following transplantation. Most recently,
      successful allogeneic transplantation of PBPCs has been reported without
      increasing the incidence and severity of acute graft-versus-host-disease. Due to
      the more than one log higher number of lymphoid subsets contained in a PBPC
      allograft, one might expect a more pronounced graft-versus-leukemia effect in the
      transplant patient. Similar to BM cells, ex vivo manipulation of mobilized
      apheresis products is used or being developed (ultralight density percoll
      gradient, CD8 depletion, selection of graft facilitating cells, CD34+ cell
      purification and others). The transduction and long-term expression of marker
      genes and, most recently, therapeutic genes (e.g., MDR-1) in PBPCs have been
      successfully demonstrated by several groups in patients with hematologic
      malignancies and selected solid tumors. It is expected that, based on the easier
      procurement of hematopoietic stem cells and advantageous engraftment
      characteristics, PBPCs in both autologous and allogeneic transplant situations
      will eventually replace BM-derived progenitor cells.

PMID- 8991539
TI  - Dendritic cells: origin and differentiation.
AB  - Dendritic cells (DC) are bone marrow-derived cells that are specialized to take
      up, process and present antigen, and have the capacity to stimulate resting T
      cells in the primary immune response. DC are a unique population that is likely
      to derive from a myeloid precursor cell. DC differentiation from bone marrow
      precursors in enhanced by the cytokines GM-CSF and tumor necrosis factor-alpha.
      In contrast, it has been proposed that thymic DC and T cells arise from a common
      stem cell, and that these DC play a specific role in the negative selection of
      thymic T cells. A number of post-bone marrow differentiation stages can be
      defined phenotypically and functionally. Undifferentiated DC have very active
      endocytic pathways, including receptor-mediated endocytosis involving a
      mannose/beta glucan receptor, and macropinocytosis of soluble antigen. In
      contrast, later stages of maturation are associated with a decreased ability to
      take up and process antigen, and increasing expression of major
      histocompatibility complex, adhesion and costimulatory molecules. Finally,
      activation of DC for full antigen-presenting cell function can be identified by
      the expression of CD28 ligands. The inflammatory site in rheumatoid arthritis is
      a human model of DC differentiation in response to a chronic antigenic stimulus.
      The features of this DC model are discussed.

PMID- 8991540
TI  - Thrombopoietin-stimulated ex vivo expansion of human bone marrow megakaryocytes.
AB  - The effect of thrombopoietin (TPO) on megakaryocytopoiesis (MKP) has been mainly
      studied using clonogenic assays in murine systems. In this study, we evaluated
      MKP in liquid culture using human bone marrow cells. While interleukin 3 (IL-3)
      and stem cell factor (SCF) are potent activators of TPO-stimulated MKP in the
      murine system, only IL-3 exhibited synergistic activity with TPO in cultures of
      human bone marrow. The IL-3 effect on TPO-stimulated megakaryocyte (MK)
      proliferation, expressed as the absolute number of MKs per seeded CD34+ cell, was
      more pronounced with purified CD34+ cell (8 +/- 1.6 SE versus 2.8 +/- 0.7 SE in
      the presence and absence of IL-3, respectively) than with mononuclear cells (MNC)
      (16 +/- 2.8 SE versus 11 +/- 2.0 SE). This effect of IL-3 on TPO-stimulated MK
      proliferation was due to a general proliferation of all cell types since the
      relative frequency of MKs (32.1 +/- 3 SE and 55.8 +/- 3 SE in MNC and CD34+
      cells, respectively) was not affected by IL-3. The effect of TPO alone, TPO + IL
      3, TPO + SCF, and TPO + IL-3 + SCF on MK proliferation was examined in MNC and
      CD34+ cultures. Greater numbers of MK per seeded CD34+ were observed in MNC
      compared to CD34+ cultures under all conditions except when TPO was added with
      both IL-3 and SCF. The enhancing effect of MNC was also observed on MK ploidy in
      the presence of TPO and IL-3. While proliferation and ploidy increase with TPO
      concentration in the murine system, they are inversely related in the human
      system. A significant 2.5-fold enhancement of TPO-induced MK proliferation was
      observed when purified CD34+ cells were cultured in inserts separated from human
      bone marrow stroma, indicating that soluble stimulatory factors are released from
      the stroma. These observations will be useful for ex vivo expansion of MKs to
      treat post-transplant or chemotherapy-associated thrombocytopenia.

PMID- 8991541
TI  - Inhibition of enriched stem cells in vivo and in vitro by the hemoregulatory
      peptide SK&F108636.
AB  - Replacement of the labile sulfhydryl group (-SH) of the hemoregulatory peptide
      monomer pyroGluGluAspCysLys (HP5b) with an isosteric methylene group yields a
      chemically stable compound, SK&F108636. In this study, we describe the effects of
      SK&F108636 on highly enriched Lin-Sca1+ hematopoietic stem cells. SK&F108636
      significantly reduced the fraction of cycling progenitor cells, granulocyte
      macrophage colony-forming cells (GM-CFC), in vitro and in vivo. There was no
      effect on GM-CFC or Mix-CFC colony formation. SK&F108636 significantly inhibited
      proliferation of high proliferative potential (HPP)-CFC in semisolid agar
      cultures stimulated by stem cell factor + interleukin 3 (IL-3) + IL-1, but had no
      effect in cultures stimulated with M-CSF + IL-3 + IL-1. SK&F108636 was shown to
      act directly on the stem cells since SK&F108636 inhibited proliferation of Lin
      Sca1+ cells in single cell assays. Administration of SK&F108636 to lethally
      irradiated mice transplanted with 2000 Lin-Sca1+ cells significantly inhibited
      proliferation/differentiation of cells developing into colony forming units
      spleen (CFU-S) (preCFU-S) and the reconstitution of HPP-CFC and GM-CFC. There was
      no effect of SK&F108636 on CFU-S colony formation or mature cell regeneration in
      bone marrow, spleen and blood. Hence, the hemoregulatory peptide monomer
      SK&F108636 is a potent primitive stem cell inhibitor in vivo and in vitro.
      Inhibition of stem cell proliferation by small specific inhibitors may protect
      hematopoiesis from myelotoxic side effects during chemotherapy treatment.

PMID- 8991542
TI  - Endogenously produced interleukin 6 is an accessory cytokine for dendritic cell
      hematopoiesis.
AB  - The aim of this study was to investigate the role of interleukin 6 (IL-6) in
      normal dendritic cell (DC) hematopoiesis. We used an enzyme-linked immunosorbent
      assay to quantitate IL-6 levels in CD34+ progenitor cell cultures favoring
      monocyte (mono) development versus those supporting mono-DC growth, and studied
      the neutralizing effects of alphaIL-6 antibody on DC hematopoiesis. IL6 levels in
      mono cultures (GM-CSF alone) were detected by day 4 and remained constant
      (approximately 100+ pg/ml) for 18 days. In mono-DC cultures, higher IL-6 levels
      correlated with DC content and development. Short-term mono-DC cultures initiated
      with GM-CSF + tumor necrosis factor (TNF) + stem cell factor (SCF) exhibited
      increases in IL-6 level until day 11 (peak DC growth). By day 18, the levels had
      declined and cells expressing typical DC features were no longer present. Long
      term mono-DC cultures sustained with GM-CSF + TNF + SCF contained the highest IL
      6 levels (671 pg/ml) on day 11. In these cultures, DCs and higher IL-6 levels
      persisted beyond 18 days. Anti-IL-6 profoundly inhibited cell proliferation
      associated with DC hematopoiesis when added on days 0, 2 and 5 to GM-CSF + TNF +
      SCF cultures, indicating that various stages of mono-DC development rely on IL-6.
      There was no reduction in the T cell response when alphaIL-6 was added to mixed
      leukocyte reaction cultures containing mature DCs as stimulators. Thus, alphaIL-6
      appears to downregulate developmental processes associated with optimal mono-DC
      growth, but not the effector functions of mature DCs. These studies substantiate
      the importance of IL-6 as a secondary cytokine during DC development and provide
      insight into another control point in the DC pathway.

PMID- 8991543
TI  - Long-term expression of human growth hormone (hGH) in mice containing allogeneic
      yolk sac cell derived neovascular implants expressing hGH.
AB  - We have established a systemic gene delivery animal model system by using
      cultured murine embryonic yolk sac cells, which can be easily genetically
      modified in vitro and participate in angiogenesis in vivo when basement membrane
      proteins (Matrigel) are provided in syngeneic mice. In the present study, we
      successfully applied this system to allogeneic mice. In order to suppress donor
      cell-specific immune responses, the costimulatory signal transduction pathway of
      T cell activation was blocked by treating the recipient allogeneic C57BL/6 mice
      with rat-antimouse B7.2 antibody. As a result of this suppression, human growth
      hormone, the therapeutic gene product, could be detected for over 340 days, while
      it could only be detected in mice treated with rat-IgG2a, the iso-type control of
      anti-B7.2, for fewer than 50 days. This is the first ex vivo gene delivery system
      that can express a therapeutic gene product, long-term, in an allogeneic host.

PMID- 8991545
TI  - [Silent mutations in the region of overlapping genes].

PMID- 8991544
TI  - Differential expression of telomerase activity in hematopoietic progenitors from
      adult human bone marrow.
AB  - The loss of telomeric DNA may serve as a mitotic clock which signals cell
      senescence and exit from cell cycle. Telomerase, and enzyme which synthesizes
      telomeric repeats de novo, is required to maintain telomere lengths. In humans,
      significant telomerase activity has been found in cells with essentially
      unlimited replicative potential such as reproductive cells in ovaries and testes,
      immortal cell lines and cancer tissues, but not in most normal somatic cells or
      tissues. We have now examined telomerase expression in subpopulations of
      hematopoietic cells from adult human bone marrow using a sensitive polymerase
      chain reaction-based telomeric repeat amplification protocol. Telomerase activity
      was found at low levels in the highly enriched primitive hematopoietic cells
      (CD34+CD71loCD45RAlo) and was increased transiently when these cells were
      cultured in the presence of a mixture of cytokines. In contrast, the early
      progenitors (CD34+CD71+) expressed telomerase activity at a higher level which
      was subsequently downregulated in response to cytokines. Telomerase activity
      remained low in the more mature CD34-cells upon exposure to cytokines. Taken
      together, our results suggest that telomerase is expressed at a basal level in
      all hematopoietic cell populations examined, is induced in a primitive subset of
      hematopoietic progenitor cells and is downregulated upon further proliferation
      and differentiation of these cells. We have previously observed telomere
      shortening in cytokine-stimulated primitive hematopoietic cells. The low and
      transient activation of telomerase activity described here thus appears
      insufficient to maintain telomere lengths in cultured hematopoietic cells.

PMID- 8991546
TI  - [Prophenin and PR39X--novel antimicrobial leukocyte peptides regulating
      functional activity of thrombocytes].

PMID- 8991547
TI  - [The Rhizobium leguminosarum bv viciae VF39 pssB gene product participates in
      symbiotic fixation of molecular nitrogen].

PMID- 8991548
TI  - [Twenty years of work at the Clinic for Lung Diseases of the Institute for
      Tuberculosis and Lung Diseases (1976-1996].

PMID- 8991549
TI  - [Evaluation of prognostic factors and progress of disease in patients with COPD
      treated with long-term oxygen].
AB  - Long-term sequential evolution of pulmonary function, blood gas, body mass index
      (BMI) and oxygen breathing time was observed in 266 COPD patients with advanced
      airway obstruction (FEV1 = 0.80 L), and severe respiratory failure (PaO2 = 52
      mmHg, PaCO2 = 49 mmHg) undergoing LTOT. There were significant differences
      between survivors and non-survivors at entry and during the treatment. Patients
      dying during LTOT had at entry lower BMI and more advanced airway limitation than
      survivors. They did not differ in blood gas values. During the follow-up (between
      1-4 years) different trends in evolution of studied variables were observed in
      survivors (over 4 years on LTOT) and patients dying during LTOT (up to 4 years).
      Long term stabilization of spirometric and blood gas values as well as in mean
      oxygen breathing time (14 hours) were observed in survivors. In non-survivors a
      significant progression in airway limitation and respiratory failure coupled with
      better compliance with LTOT (oxygen use increased from 15 to 17 hours/ day) was
      observed especially in the last year before death. In survivors BMI increased
      significantly during the treatment, whereas in non-survivors no change was
      observed.

PMID- 8991550
TI  - [Reproducibility of results for overnight pulse oximetry in patients with chronic
      obstructive pulmonary disease].
AB  - Overnight pulse-oximetry (PO), as the only non-invasive method assessing arterial
      blood oxygenation during sleep, became widely used additional criterion for the
      long-term oxygen therapy especially in chronic obstructive pulmonary disease
      (COPD) patients. The aim of this study was to assess the reproductibility of
      pulse-oximetry in COPD patients. We studied 20 stable COPD pts mean age 64.6 +/-
      7.2 years with severe airway obstruction-FEV1 = 0.87 +/- 0.33 L and hypoxaemia
      PaO2 = 55.8 +/- 6.9 mmHg. Three PO were performed in each patient at one and
      seven nights intervals. There were no statistically significant differences in
      results obtained at all three PO. The mean oxygen saturation changed from one
      night to another only by 0.1%, the initial and final-maximally by 0.5%. High
      correlations for mean oxygen saturation (r = 0.94 and 0.78 respectively), initial
      oxygen saturation (r = 0.78 and 0.52) and final oxygen saturation (r = 0.69 and
      0.77) were observed. In conclusion PO is reproducible in stable COPD patients at
      1 and 7 days intervals.

PMID- 8991551
TI  - [Evolution of nocturnal pulse-oximetry results in patients with chronic
      obstructive pulmonary disease].
AB  - The aim of this study was to evaluate if results of overnight pulse-oximetry (PO)
      change with time and progression of the disease. We studied 39 COPD patients.
      Majority of them (33 pts) were treated with long-term oxygen therapy (LTOT).
      Fifty pairs of PO were performed in the whole group separated from 1 to more than
      3 years. Pulmonary function tests were performed at the same time as PO. Results
      of these tests showed progressive deterioration in the lung function-decrease of
      FEV1 and PaO2. Despite of that there were no statistically significant changes in
      any variable of PO in any studied group. This phenomenon is difficult to explain.
      It may resulted from the improvement in the cardiac output observed in COPD
      patient undergoing LTOT. May be that studied groups were not large enough or time
      of observation was too short to reveal differences. Stabilization of PO results
      in spite of deterioration in the lung function in COPD patients needs more
      studies.

PMID- 8991552
TI  - [Eight years of experience in Warsaw with domiciliary long term oxygen therapy].
AB  - Between August 1986-July 1994 45 1 patients with chronic hypoxaemia were referred
      to us for evaluation. 315 of them (70%) were qualified for LTOT according to
      national guidelines. There were 189 pts with COPD (60%), 40 with late sequelae of
      pulmonary tuberculosis (TB), 21 with interstitial pulmonary fibrosis (IPF), 15
      with bronchiectasis (BE), 15 with severe kyphoscoliosis (KS) and 35 with other
      disease leading to chronic respiratory failure. All patients received oxygen from
      an oxygen concentrator and have been regularly followed-up. The best survival
      rate in patients followed up for at least 3 years was observed in KS (68%) and
      COPD pts (50%). The worst survival was seen in BE (9%) and IPF (21%). 183 pts
      died during the follow-up and in 3 pts (1%) LTOT was withdrawn. The most frequent
      cause of death were either acute (58%) or chronic (21%) cardiorespiratory
      failure.

PMID- 8991553
TI  - [Function of the diaphragm during exercise].
AB  - We examined the control of respiratory muscles with emphasis on the diaphragm
      during exercise at 30%, 60% and 90% of maximal working capacity in normal
      subjects. Control of the diaphragm was quantified by plotting transdiaphragmatic
      pressure (Pdi), its electromyographic activity (Edi) and its power (Wdi = Pdi x
      Dab/Ti) vs. workload and Pdi, an index of shortening velocity of diaphragmatic
      fibres (Dab/Ti) and Wdi vs. Edi. We observed that increase in Pdi (approximately
      2-fold) from rest to heavy exercise was inadequately small comparing to increases
      in minute ventilation (approximately 9-fold) and Edi (approximately 4.5-fold). We
      hypothesized and confirmed that Wdi might increase even though Pdi decreased due
      to increasing Dab/Ti and expresses more closely diaphragmatic contribution to
      inspiratory effort during exercise than Pdi. Significantly augmented shortening
      velocity of the diaphragm suggests that it acts predominantly as a flow generator
      during exercise. It is strongly assisted in this task by abdominal muscles. The
      responsibility for generating inspiratory pressures falls on the inspiratory rib
      cage muscles. This arrangement may however impair diaphragm's performance even in
      healthy subjects as indicated by reduced Pdi twitch after exercise.

PMID- 8991554
TI  - [Effect of respiratory muscle fatigue on their function during exercise].
AB  - We evaluated the effect of global inspiratory muscle fatigue (GF) on respiratory
      muscle control during exercise at 30%, 60%, and 90% of maximal power output in
      normal subjects. Fatigue was induced by breathing against a high inspiratory
      resistance until exhaustion. Respiratory pressures, breathing pattern, and
      perceived breathlessness were measured. Induction of GF had no effect on the
      ventilatory parameters during mild and moderate exercise. It altered, however,
      ventilatory response to heavy exercise by increasing breathing frequency and
      minute ventilation, with minor changes in tidal volume. This was accompanied by
      an increase in perceived breathlessness. GF significantly increased both the
      tonic and phasic activities of abdominal muscles that allowed 1) the diaphragm to
      maintain its function while developing less pressure, 2) the same tidal volume
      with lesser shortening of the rib cage inspiratory muscles, and 3) relaxation of
      the abdominal muscles to contribute to lung inflation. The increased work
      performed by the abdominal muscles may, however, lead to a reduction in their
      strength. GF may impair exercise performance in some healthy subjects that is
      probably not related to excessive breathlessness or other ventilatory factors.
      The respiratory system is remarkably adaptable in maintaining ventilation during
      exercise even with impaired inspiratory muscle contractility.

PMID- 8991555
TI  - [Exercise tolerance in patients with chronic obstructive pulmonary disease in
      various stages of advanced disease].
AB  - The aim of the study was to investigate exercise tolerance in COPD patients.
      Eighty one subjects, 66 M and 15 F mean age 60.4 +/- 9.2 yrs, mean VC 2.56 +/-
      0.81 L, FEV1 1.00 +/- 0.47 L., PaO2 58.4 +/- 10.1 Torr, PaCO2 45.1 +/- 8.9 Torr
      were studied. A symptom limited incremental exercise test on cycloergometer using
      ramp protocol was performed. Ventilatory parameters (breath by breath method),
      together with transcutaneous oxygen saturation and heart rate (continuously) were
      recorded. Four patients tolerated only unloaded pedalling (0 Watt), others
      workload from 5 to 80 Watts, with one exception of 120 Watts and two of 100
      Watts. A significant correlation was found between VO2max and FEV1 (r = 0.67) and
      between StcO2 during exercise and StcO2 at rest (r = 0.31) and PaO2 at rest (r =
      0.45). No correlation was found between VO2max and blood gases at rest and
      exercise. Exercise tolerance in COPD patients could be predicted from airway
      limitation. Patients with severe COPD presented with a disturbed anaerobic
      metabolism during exercise and in 18 of them anaerobic metabolism was present
      already at rest. A significant correlation was found between blood gas values at
      rest and StcO2 during exercise.

PMID- 8991556
TI  - [Prognostic value of pulmonary hypertension in patients with severe COPD].
AB  - There is a continuing debate on the role of pulmonary hypertension in the natural
      history of COPD. The aim of the study was to compare 2 groups of COPD pts, one
      investigated before domiciliary oxygen treatment era (Group I) with the other
      benefiting from LTOT (Group II). Both were followed-up for 5 years. INCLUSION
      CRITERIA: pure COPD, PaO2 < 60 mmHg, PAP > 20 mmHg. Group I consisted of 16 pts
      (13M, 3F), mean age 55 +/- 9y. On initial evaluation their FEV1 averaged 0.93 +/-
      0.3L and PaO2 54 +/- 6 mmHg. Their mean pulmonary arterial pressure (PAP) was
      37.9 +/- 9 mmHg. During five years 12 patients (75%) died. Mean survival time of
      pts who died was 18.9 +/- 14.7 months. Group II consisted of 34 pts (27M, 7F)
      mean age 56 +/- 8y (NS vs group I), FEVI 0.83 +/- 3L (NS). PaO2 53 +/- 6 mmHg
      (NS), PAP 30.9 +/- 8.5 mmHg (p < 0.02). During five years 26 pts (76.5%) died.
      Mean survival time was 25 +/- 16 months (NS). Mean oxygen breathing time was 14h/
      day. The Cox's survival analysis did not show difference between patients group I
      and II. We conclude that high initial PAP in group I patients did not affect
      survival compared to patients with similar severity of respiratory failure and
      lower PAP. The finding that LTOT did not improve survival may depend on many
      other variables not included into analysis.

PMID- 8991557
TI  - [Evaluation of emphysema progression as measured by computed tomography in
      patients with chronic obstructive pulmonary disease].
AB  - It has been difficult to assess the progression of pulmonary emphysema since
      accurate quantification of the extent of this condition has only previously been
      possible on post mortem or resected lungs. Previously we have shown that
      measurements of CT lung density correlated with the degree of emphysema, measured
      morphometrically in resected lungs. We have therefore employed this technique to
      assess the progression of emphysema in 17 patients (12M, 5F) with wide range of
      chronic airflow limitation (FEV1 15-68% predicted). There was little change in
      the degree of airflow limitation, hyperinflation or arterial blood gas values
      over 30 +/- 4 months of follow up (p > 0.05). However during this period there
      was a significant decrease in the lowest 5th percentile of CT density, which fell
      from -920 +/- 32 to -940 +/- 36 Hounsfield units (p < 0.005) associated with
      significant fall in the diffusing capacity for carbon monoxide. We believe that
      these data show the ability of CT scanning to assess the progression of emphysema
      in patients with chronic obstructive pulmonary disease.

PMID- 8991558
TI  - [Levels of atrial natriuretic peptide in stable and exacerbated chronic
      obstructive pulmonary disease].
AB  - Plasma Atrial Natriuretic Peptide (ANP) levels are elevated in patients wish
      chronic obstructive pulmonary disease (COPD) and can play a role in oedema
      formation. Plasma ANP levels measured in 60 patients with COPD were compared with
      results of pulmonary haemodynamics, with therapeutic response to treatment in the
      time of exacerbation of COPD and with physiologic status of patients with stable
      COPD. Plasma ANP levels did not correlate with right atrial and pulmonary artery
      pressure, but were significantly related with right ventricular end diastolic
      volume and with right ventricular wall volume measured by magnetic resonance
      imaging. Oxygen breathing (2 l/min by nasal prongs in 30 min.) did not change
      either mean pulmonary artery pressure or ANP levels. Among patients studied
      during an acute exacerbation of COPD, plasma ANP levels were higher in patients
      with oedema (302 +/- 185 pg/ml) than in patients without oedema (87 +/- 43
      pg/ml). Oxygen therapy applied in one hour did not influence plasma ANP levels.
      Plasma ANP levels decreased during first three days of treatment in patients with
      oedema. This decrease was related to the body weight. In the group of patients
      with hypoxemia in stable COPD, plasma ANP levels (120 +/- 50 pg/ml) were higher
      in patients with the history of hypercapnia and oedema than in others (54 +/- 15
      pg/ml).

PMID- 8991559
TI  - [Pulmonary circulation at rest and during exercise in patients with obstructive
      sleep apnea before and after one year of treatment with CPAP].
AB  - We studied pulmonary haemodynamics in 19 male patients, mean age 45 +/- 5 years,
      suffering from severe OSA, mean apnea/hypopnea index (AHI) 68 +/- 17. Pulmonary
      haemodynamisc were studied using Swan-Ganz thermodilution catheter in the supine
      position at rest, and at the end of the 7th minute of steady-state exercise (40
      W). Investigations were repeated after one year of treatment with nasal CPAP. At
      rest mean pulmonary artery pressure (PPA), pulmonary wedge pressure (PW) and
      cardiac output (CO) were normal, PPA = 16.6 +/- 5.7 mmHg, PW = 5.2 +/- 1.8 l/min.
      Pulmonary vascular resistance (PVR) was slightly elevated = 155 +/- 65 d.sec.cm
      5. On exercise only PVR remained unchanged. After a year of treatment PPA changed
      to 15.8 +/- 4.0 mmHg (NS), Pw-7.5 +/- 3.1 mmHg (NS), CO-4.9 +/- 1.6 L/min (NS),
      PVR - 145 +/- 35 d.sec.cm-5 (NS). In two patients with resting hypertension PPA
      dropped from 33 mmHg to 25 mmHg and 28 mmHg to 18 mmHg respectively. Statistical
      analysis showed no significant change in any of the studied variables after one
      year of the CPAP therapy.

PMID- 8991560
TI  - [Evaluation of a Polish apparatus for creating continuous positive airway
      pressure (nCPAP)].
AB  - The aim of the study was to evaluate technical features of polish CPAP machine
      and to compare its parameters with two commonly used models of foreign origin.
      Physical signs, noise, produced flows and pressures were compared. POL-CPAP was
      bulkier and noisier than foreign models. Flows and pressures were not completely
      satisfactory. We conclude that POL-CPAP fulfill the criteria required from such
      type of equipment. However the evaluated device requires further improvement of
      technical parameters.

PMID- 8991561
TI  - [Quality of sleep and periodic breathing during sleep in healthy persons at a
      height of 3200 meters].
AB  - In order to investigate quality of sleep and sleep-related breathing disorders
      (SRBD) at high altitude we performed full polysomnography in 9 young healthy
      volunteers at lowland (760 m above see level) and on the 1st and 6th night after
      the ascent to the altitude of 3200 m. The subjects were non-smoking males aged
      20.3 +/- 3.5 years with normal spirometry and arterial blood gas measurements
      performed at low altitude. We found no statistical difference in sleep quality
      between low and both nights at high altitude as considered by % of stages 1, 2, 3
      + 4 non-REM, and REM sleep, total sleep time, sleep efficiency, and number of
      awakenings+arousals. There was no periodic breathing (PB) during sleep but some
      central events of SRBD at low altitude. PB appeared at high altitude mostly
      during non-REM sleep and remained stable throughout the study period. There were
      also some obstructive SRBD found during high altitude nights. Mean SaO2 was lower
      during both nights at high altitude when compared to low altitude (p < 0.00001).
      It was higher during the 6th than during the 1st night at altitude (p < 0.0001).
      Minimum SaO2 was comparable during low altitude and 6th night at altitude and was
      lower during the 1st altitude night (p < 0.02). We conclude that sleep quality at
      the altitude of 3200 m remains unchanged when compared to lowland. There is high
      individual variability in PB at altitude and its intensity is negligible.

PMID- 8991563
TI  - [Effect of CPAP and BiPAP assisted breathing on pulmonary hemodynamics in
      patients with obstructive sleep apnea].
AB  - CPAP breathing increases alveolar and intrathoracic pressures. We aimed to
      investigate the effects of CPAP and BiPAP breathing on pulmonary haemodynamics in
      patients with OSA. Ten male patients with OSA (AHI = 48 +/- 22) were studied. In
      each patient intravascular and esophageal pressures were measured and mean
      transmural pulmonary artery and transmural wedge (Pwtm) pressures were
      calculated. After baseline recordings patients were submitted to 25 min. of CPAP
      and BiPAP breathing in random order. The pressure of 10 cm H20 for CPAP and 10/4
      cm H20 for BiPAP was used. At baseline pulmonary arterial pressures and flow were
      normal. CPAP breathing resulted in an increase in mean pulmonary intravascular
      pressure from 15.5 +/- 1.8 mmHg to 17.1 +/- 2.3 mmHg (p < 0.05). Transmural
      pressure did not change. There was also no change in the cardiac output (CO) and
      pulmonary vascular resistance (PVR). At some time points pulmonary arterial
      pressures were higher during CPAP breathing than during BiPAP breathing (p <
      0.01). BiPAP breathing had no effect on intravascular and transmural pressures,
      CO and PVR. We conclude that CPAP breathing increase pulmonary intravascular but
      not transmural, true, pressure. BiPAP breathing does not change pulmonary
      haemodynamics what may be of importance as pulmonary circulation is concerned.

PMID- 8991562
TI  - [Effect of altitude on blood oxygenation during sleep in patients with bronchial
      asthma].
AB  - The aim of our study was to investigate the severity of overnight arterial blood
      desaturations in patients with asthma at the altitude of 3200 meters above sea
      level. 12 asthmatics and 12 healthy controls were investigated. Three overnight
      pulsoximetries were performed in all subjects, one at the lowland and on the 1st
      and 5th night at the altitude. Mean SaO2 at the lowland was significantly lower
      in asthmatics than in the controls (p < 0.01). After the ascent to high altitude
      severe fall in mean SaO2 was noted in both groups (from 94.3% to 85.8% in
      asthmatics and from 97.1% to 88.7% in controls) (p < 0.001 for both groups).
      After few days of acclimatization mean SaO2 rose to 88.8% in asthmatics and to
      91.3% in controls, but was still significantly lower than at the lowland (p <
      0.001 for both groups). At the altitude differences in mean SaO2 between two
      groups were not statistically significant. We conclude that severity of overnight
      desaturations at high altitude do not vary between asthmatics with impaired
      respiratory function and healthy subjects.

PMID- 8991564
TI  - [Co-stimulating effect of extracellular matrix proteins on T lymphocyte
      proliferation in patients with sarcoidosis. Preliminary tests].
AB  - Although very little is known about the aetiology of sarcoidosis, its
      immunopathogenesis is now better known. The interaction of alveolar macrophages
      and T cells may play a role in the pathomechanism of the disease. To infiltrate
      the tissue, lymphocytes have to migrate through the subendothelial basement
      membrane and interstitium, rich in extracellular matrix (ECM). The interaction of
      lymphocytes with proteins of the ECM may play an important role in the migration,
      accumulation and activation of these cells. The aim of our study was to estimate
      the ability of the ECM components (collagen I, collagen IV and fibronectin) to co
      stimulate T-cells in patients with sarcoidosis. The peripheral blood was obtained
      from 14 sarcoid patients. The disease was confirmed histologically in 9 cases and
      in 5 patients on clinical grounds. In radiological findings 4 persons were at the
      first stage of the disease, 4 at the second, in three cases interstitial changes
      were found and in three patients, the fibrosis on the X-ray was noticed. No one
      of those patients were treated with steroids during last 2 months. Normal
      peripheral blood T cells are strongly co-stimulated by ECM proteins. In contrast,
      lymphocytes from patients with sarcoidosis were inhibited by the ECM proteins.
      The mean co-stimulation ratios (OKT3 + ECM proteins:OKT3 alone) were
      significantly lower for all ECM proteins (collagen I: p < 0.00009; collagen IV: p
      < 0.02; fibronectin: p < 0.04). Our data shed a new light on the nature of
      sarcoidosis associated immunodeficiency and suggest that disturbed T cells: ECM
      interactions may play a role in the pathogenesis.

PMID- 8991565
TI  - [Lung function and exercise tolerance in patients with chronic major vessel
      thromboembolic pulmonary hypertension].
AB  - We studied 14 consecutive patients with severe pulmonary hypertension due to
      chronic major vessel thromboembolic pulmonary hypertension (CPTEH), clinical
      entity that may be successfully surgically treated by pulmonary
      thrombendarterectomy. Resting pulmonary mechanics and gas exchange were
      investigated. Exercise tolerance was studied by 3 different exercise tests.
      Pulmonary volumes and flows were normal. Some patients presented with decreased
      lung compliance and reduced diffusion capacity for carbon monoxide. Majority of
      patients had hypoxaemia and respiratory alkalosis. Exercise tolerance was very
      limited. In 6 minute walking test patients covered 346 +/- 95 meters. During
      Bruce test patients completed from 1 to 4 stages. During incremental maximal
      symptom limited test on cycloergometer patients achieved 56 +/- 18 watts. We
      concluded that patients with CPTEH present with resting hypoxaemia deteriorating
      further on exercise and severely limited exercise tolerance.

PMID- 8991566
TI  - [Obesity and hypoventilation syndrome; effects of weight loss and treatment with
      respiratory stimulants].
AB  - A 32-year-old, hypertensive, morbidly obese (BMI 49 kg/m2) woman was referred to
      us suspected of sleep-disordered breathing. Polycythaemia, right heart and
      respiratory failure, restrictive ventilatory impairment, decreased hypercapnic
      respiratory drive, high number of very short apneas mostly of central origin (698
      vs 530 obstructive), and overnight hypoxaemia were found. The diagnosis of
      obesity-hypoventilation syndrome was established and the treatment with
      almitrine, aminophylline and low-calorie diet was started. After 6 months body
      weight decreased significantly (BMI 38 kg/m2). RBC, spirometry, blood gas
      analysis, overnight oximetry, hypercapnic respiratory drive and polysomnography
      showed results within normal limits. Causes, pathophysiology and possible
      treatment of obesity-hypoventilation syndrome are discussed.

PMID- 8991567
TI  - [Function of the respiratory muscles].

PMID- 8991568
TI  - [Qualification of human body reactions to microgravity].
AB  - The purpose of this paper is to qualify developments in the human body during
      long-term exposure to microgravity in the light of current physiological and
      pathophysiological postulates. The work is grounded on the analysis of the data
      about human body reactions to extended stay in microgravity and adopted from the
      literature. The syndrome of space motion sickness (SMS) evolving at the onset of
      space flight can be qualified as a temporary reaction to inadequate ambient
      conditions. In long-term microgravity after mitigation of SMS by dint of
      appropriate countermeasures, no subjective disturbing symptoms are virtually
      present. Performance remains on a sufficiently good level, and the body develops
      stable adaptive reactions and establishes an adequate homeostasis. Back to Earth,
      the human body undergoes a number of changes which can be qualified as a
      transient gravity-induced syndrome associated with readaptation of partly
      deconditioned body to the normal gravity forces.

PMID- 8991569
TI  - [Optico-electronic medical equipment and perspectives of its use in space
      medicine and biology].
AB  - On literary evidence, the authors analyze principles of operation of
      optoelectronic equipment, contemplate its merits and advantages in comparison
      with other known methods of attacking various problems of practical medicine and
      direct the ways of its application in space biology and medicine.

PMID- 8991570
TI  - [Optimal isotope composition of biogenic chemical elements on board of manned
      spacecrafts].
AB  - Isotope composition of biogenic chemical elements (BCE) is discussed. A
      hypothesis is offered that biochemical and biomedical processes must be
      influenced as by the isotope composition of hydrogen and oxygen, so by the
      composition of stable isotopes of all the BCE constituting plants, animals, and
      humans. Biochemical, toxicological and other biomedical analyses should be
      performed to determine the best BCE isotope composition. These must be followed
      by development of methods, technologies, and life support systems to form and
      maintain the best isotope composition inside spacecraft habitable modules.

PMID- 8991571
TI  - [Effects of preliminary loading on dynamic strength of the spine].
AB  - The purpose of this work was to evaluate early and delayed effects of static
      mechanical loading of the spine on human tolerance to the ejection g-loads.
      Experiments with spine segments showed that static pre-loading equivalent to
      aerobatic accelerations of 8-10 units leads to relative strengthening of vertebra
      with low tolerance of the longitudinal shock load. Effect of aerobatic
      accelerations of 5, 6, 7, and 8 units on ejection g-load tolerance was
      theoretically evaluated.

PMID- 8991572
TI  - [Compensatory reactions of the rabbit respiratory system to hypoxic stimulation
      in hyperbaric conditions].
AB  - Two series of experiments were performed with awake rabbits to study ventilatory
      reactions of the respiratory system to hypoxic stimulus. Two types of tests
      included alternating exposure to hypoxic mixture with 14%, 12%, and 10% of O2
      (for 10 min) and rebreathing (12% O2 + 4.5% CO2) with concurrent sampling of
      arterial blood for gas analysis. The experiments were performed under the
      atmospheric pressure and in the nitrogen-oxygen air at 0.6, 1.0, 1.3, 1.5, 2.0,
      and 3.0 MPa. Both of the tests disclosed a distinct reduction of pulmonary
      ventilation gain in hyperbaric conditions due to inhalation of a hypoxic mixture.
      In the experiment with alternating exposure to hypoxic mixtures the gain
      reduction was gradual and correlated with a pressure rise. During rebreathing,
      hypoxemia appeared as early as the first minutes of experiment. PaCO2 grew by the
      end of exposure and abrupt inhibition of the ventilatory reaction occurred even
      at 0.6 MPa. Sharp degrees of hypoxemia during rebreathing seemed to suppress the
      respiratory center to the extent at which the reaction to hypoxia became weaker
      rather than stronger and was manifested by a sudden attenuation. These results
      suggest that hyperbaric conditions reduce the ventilatory reaction to hypoxia and
      balancing potentials of the respiratory system, and impair the respiration
      controls.

PMID- 8991573
TI  - [Changes in the enzyme-active region of the neuromuscular synapse of the
      gastrocnemius muscle in rats during hypokinesis].
AB  - Restraint of white rats in fight cages leads to diminution of the area of
      neuromuscular synapse with an intricate structure of the enzyme-active region and
      reduction of the number of neuromuscular synapses per one fiber in the
      gastrocnemius muscle. Signs of dystrophy of neuromuscular synapses with the
      intricate enzyme-active region are observed. These changes arise by day 14 of
      hypokinesia and become more pronounced by day 28.

PMID- 8991575
TI  - [Role of hypoxia in the development of epileptiform seizures].
AB  - The article reviews the factors of abiotic and biotic environments liable to
      provoke convulsions. An assumption is made that the common element of their
      action on the organism are hypoxic states of varying types and depth. Animals
      with high individual tolerance of acute hypoxia were found to possess a better
      resistance to the convulsing effect of penicillin. In these animals the epilepsy
      form discharges appear with longer latent periods and the epilepsy-form seizures
      are generated much more seldom in contrast to rats with poor tolerance of
      hypoxia. Training of resistless rats in the altitude chamber increases their
      ability to oppose the convulsing effect of penicillin to the level of animals
      with moderate but not high hypoxia tolerance.

PMID- 8991574
TI  - [Memory disorders due to extreme impacts and their pharmacological correction].
AB  - The review encompasses the author's and literary data concerning effects of
      various extreme impacts, i.e. SHF electromagnetic radiation, motion sickness,
      hypoxia, etc. on the cognitive and memorizing processes in humans and animals.
      Potentials for pharmacological correction, with nootropic drugs in the first
      place, of anamnestic disorders consequent to various extreme impacts are
      considered. Possible mechanisms of the protective action of pharmacological
      substances are analyzed.

PMID- 8991576
TI  - [Combined radiodiagnosis of urinary calculi in flying personnel].
AB  - This work was to assess effectiveness of radiation investigations in the
      diagnostics of cholelithiasis in flying personnel. Examined were 217
      cholelithiasis patients from the flying personnel including 50 fighter, 67
      transport, 31 long haul and 69 helicopter pilots. All the pilots passed USI in
      real time, survey and excretory urography, radio-isotope renography and X-ray
      computerized tomography on indication. The paper review the present-day aspects
      of radiation diagnostics of cholelithiasis in flying personnel. Semiotic signs of
      concrement fragmentation during treatment with the method of remote shock-wave
      lithotripsy were specified. The most characteristic features of their evacuation
      from the urine system were described. As was demonstrated, USI of flying
      personnel is the method of choice in diagnostics of renal and gall concrements
      but of little use in localizing concrements in ureter where the survey and
      excretory urography are prioritized.

PMID- 8991577
TI  - [Indicator of adrenoreceptors in cell membranes: reference values and informative
      validity in the assessment of the functional state of the cardiovascular system].
AB  - A new method of individual determination of sympathoadrenal activity (SAA) uses
      the parameter of beta-adrenoreception in cell membranes (beta-ARM) based on the
      erythrocyte model. Correlation of an individual reference beta-ARM value with
      specific features of hypertension states, and CVS responses to psychoemotional
      stress was studied. Described are the method, and normal distribution of
      individual beta-ARM values in healthy flyers, aviation students, non-flyers, and
      aviators with diagnosed the neurocirculatory dystonia of hypertensive type and
      patients with the hypertonic disease of 2nd stage (the overall numbers of
      subjects = 221). Another group of healthy subjects and patients with the
      hypertonic disease of 1st stage and different reference beta-ARM values (n = 39)
      participated in determination of HR and BP levels during the verbal count test.
      On the evidence of individual beta-ARM distribution in the test groups, the upper
      limit of the beta-ARM physiological norm (16.0 arbitrary units) was suggested to
      be a critical parameter in diagnosis of a hyperadrenergic state. Analysis of
      hemodynamics and the quality of verbal count during performance of a
      psychoemotional test by subjects with varying reference beta-ARM values revealed
      hyperreactive cardiovascular systems in and less successful fulfillment of the
      count test by subjects with high beta-ARM.

PMID- 8991579
TI  - Publications. Atlas at the head of its class.

PMID- 8991578
TI  - [Contribution of Harald von Beckh to the development of aerospace medicine].

PMID- 8991580
TI  - [Chronic pelvic pain: searching for the "psychological factor"].

PMID- 8991581
TI  - [Is embryo research necessary? If yes, what are the limits and constraints?].

PMID- 8991582
TI  - [Is human embryo research necessary? What are the limits of animal
      experimentation?].

PMID- 8991584
TI  - [Pelvic ultrasonography in the adolescent].

PMID- 8991583
TI  - [Treatment of breast cancer during pregnancy].
AB  - Breast cancer occurring during pregnancy is a rare clinical situation. A
      multidisciplinary approach is needed involving an obstetrician a medical
      oncologist and a surgeon. It should be treated according to the same principles
      applied in non pregnant patients. Abortion or termination of pregnancy don't
      improve survival. Decisions regarding abortion should be based on the desires of
      the patient and on therapeutic necessities. Surgery if necessary is always
      possible, radiation therapy should be avoided by reason of fetal toxicity,
      chemotherapy if absolutely necessary is possible after the first trimester.

PMID- 8991586
TI  - [Role of surgery in the treatment of infertility due to polycystic ovaries].

PMID- 8991585
TI  - [What did hormonal contraception change for women?].
AB  - A major date and a major change for our society, hormonal contraception had to
      battle against law and against medicine. Changing women's status, it gave them a
      new freedom. But what of the traditional role models, man and woman's
      relationship to each other, what of their approach to love and sexuality? That is
      the question...

PMID- 8991587
TI  - [Endometrial cancer: total simple hysterectomy or radical hysterectomy? Abdominal
      or vaginal route?].
AB  - Total abdominal hysterectomy and bilateral salpingo-oophorectomy has long been
      the standard surgical treatment for endometrial cancer. Radical hysterectomy is
      not useful in stage I. in women with extreme obesity and medical risk factors,
      vaginal hysterectomy is recommended. Laparoscopy-assisted vaginal hysterectomy
      complete the oncologic treatment if lymphadenectomy is necessary.

PMID- 8991588
TI  - [Role of hormones in sexual dysfunctions, homosexuality, transsexualism and
      deviant sexual behavior: diagnostic and therapeutic consequences].
AB  - Hormones only play a minor role in sexual dysfunctions. They are clearly involved
      only in erectile dysfunction. Total testosterone is low in 8% of those patients,
      but only 32% of them are improved with androgen therapy. Free testosterone is
      also electively decreased in 30% and bioavailable (non SHBG bound) testosterone
      in 15%. However androgen-therapy is still less effective in these subgroups.
      Plain hyperprolactinemia is found in only 0,7% of the cases. Half of them result
      from a pituitary adenoma. The other endocrine dysfunctions are still scarcer.
      This data cannot justify a systematic determination of serum prolactin and
      testosterone in sexual dysfunctions. A cost effective hormonal screening is
      proposed, whereas the role of androgen-therapy in erectile dysfunction with or
      without hypogonadism is discussed. The hypothesis of an "inverted brain sexual
      differentiation" in homosexuality and for transsexualism, resulting from an
      abnormal antenatal endocrine milieu is reviewed. It cannot obviously explain by
      itself these conditions, but some amazing morphological findings in transsexual
      people do not permit to totally refute it. Lastly the role of androgens in
      paraphilia and parapaphilia related disorders seems limited to the arousal of an
      abnormal sexual behaviour previously scheduled by non hormonal mechanisms.
      However anti-androgens are in such cases one of the main effective treatment.

PMID- 8991589
TI  - [Influence of nomegestrol acetate on the improvement of the quality of life
      induced by estrogen therapy in menopausal women].
AB  - Estrogen replacement therapy in postmenopausal women is followed by several
      benefits including a prompt improvement of quality of life. Due to uterine
      proliferation induced by prolonged estrogen intake, progestogens are usually
      associated, on a cyclical basis, in hormonal replacement therapy prescribed to
      non-hysterectomized women. Persistence of the beneficial effect of estrogen on
      quality of life, during progestogens intake, was never investigated. We
      evaluated, through a specific and previously validated questionnaire, the changes
      in quality of life observed in 351 women recently menopaused, after 6 months of
      hormonal replacement therapy associating 24 days of estrogens and 12 days of
      administration of a non androgenic progestogen: nomegestrol acetate. Patients
      were randomized within two therapeutic groups in which evaluation of quality of
      life was performed either during the administration of estrogen alone or during
      administration of estrogen and progestogen. In the two groups, hormonal
      replacement therapy was followed by a significant improvement (P < 0,001) in
      quality of life and no significant difference was observed between the changes
      observed during estrogen or estrogen-progestogen administration. Quality of life
      indices measured after 6 months of hormonal replacement therapy are within the
      same range than values previously described in eugonadal women. We conclude that
      improvement of quality of life induced by estrogen replacement therapy remains
      unchanged during cyclical administration of nomegestrol acetate.

PMID- 8991590
TI  - [Orthotopic autografts of ovarian slices in pregnant rats].
AB  - We carried out orthotopic autografts of ovarian tissue on 15 Wistar rats. One
      ovary has been removed and cut in 2 or 3 slices. The other ovary has been
      removed, and the controlateral slices grafted in the empty ovarian bursa by mean
      of a microscope, without vascular anastomosis. The endocrine function of the
      graft was assessed by checking the vaginal smears. The animals were mated. Two of
      them became pregnant with normal offsprings, two others has vaginal bleeding
      which could be miscarriages. This experimentation suggests that the orthotopic
      autograft of ovarian slices is possible in rats. The endocrine function of the
      ovary is restored with a very good rate. Fertility is restored for a small
      proportion of animals.

PMID- 8991591
TI  - Proceedings of the 4th International Symposium on Hyphenated Techniques in
      Chromatography and Hyphenated Chromatographic Analyzers. Bruges, 7-9 February
      1996.

PMID- 8991592
TI  - [The inhibition of translation in vivo in Mollicutes by thiophosphate analogs of
      oligodeoxyribonucleotides].
AB  - It is shown that the concentration of "antisignature" phosphorothioate analogs of
      oligodeoxynucleotides, complementary to the region of 165 rRNA Acholeplasma
      laidlawii PG-8 and Mycoplasma fermentans PG-18 responsible tor binding with
      ribosomal protein S4 being 0.5--1 microM synthesis of proteins in vivo decreases
      to 70%. A model of mechanisms is suggested to block oligonucleotides of the
      process of in vivo translation in mollicutes by "antisignature" phosphorothioate
      analogs. The advantages of the use of antisense oligonucleotides complementary to
      functionally significant plots of 16S rRNA to inhibit the in vivo translation are
      discussed in comparison with oligonucleotides, 5-nontranslated regions of mRNA
      serving a target for them.

PMID- 8991594
TI  - [Genetic recombination during protoplast fusion in Streptomyces antibioticus, the
      producer of oleandomycin].

PMID- 8991593
TI  - [The degradation of plasticizers by Rhodococcus erythropolis 40F].
AB  - A Rhodococcus erythropolis 40 phi strain isolated from the soil utilizes 0.1-2%
      v/v dibutylphthalate (DBP) and di-(2-ethylhexyl)-phthalate (DEHP) as a single
      carbon source. The strain metabolizes DBP and DEHP via the following steps:
      diester --> phthalate --> benzoate --> p-hydroxybenzoate --> 3,4
      dihydroxybvenzoate --> 3-ketoadipinate.

PMID- 8991595
TI  - [The antimicrobial activity of thio-, thioxo- and oxo- derivatives of acridine].
AB  - Antimicrobial activity of thio-, thioxo- and oxo- derivatives of acridine has
      been studied. It was shown, that the majority of compounds possesses the moderate
      antimicrobial activity. It was established, that acetic acid (6-nitroacridinil-9
      thio), piperidine salt (2-ethoxi-6-nitroacridinil-9-thio) and ethyl ether
      (acridinil-9-thio) of acetic acid show the expressed anti-bacterial activity with
      respect to gram-positive bacteria. The ethyl ether (acridinil-9-thio) of acetic
      acid also actively suppresses the growth of similar yeast fungus.

PMID- 8991596
TI  - [The effect of bacterial polysaccharides on the course of a Mycoplasma
      infection].
AB  - Polysaccharides of Clavibacter michiganense have been studied for their effect on
      Mycoplasma infection. It is established that content of T-lymphocytes truthfully
      increased in the groups of animals whose PS 1 and PS 2 were administered both
      with protective and medical purpose as compared with that in a group of animals
      with natural course of mycoplasmosis. Under these conditions the effect of
      polysaccharides on T-helpers were not evidently expressed, while they exerted
      considerable effect on T-suppressors, normalizing their high index in the animals
      infected by Mycoplasma hominis. Polysaccharides also exerted a normalizing effect
      on the content of T-killers, whose level in the animals with natural proceeding
      of mycoplasmosis was considerably decreased. One can observe a decrease of
      content of B-lymphocytes (which approached the level of their control in a group
      of conditionally healthy animals) under the effect of polysaccharides as compared
      to infected animals. Metabolic processes are activated in immunocompetent cells
      as affected by polysaccharide. Results obtained when studying the effect of
      polysaccharides on immunologic factors in the animals with mycoplasma infection
      as well as histomorphological data confirm the above evidences that
      polysaccharides of C. michiganense are promising immunomodulators.

PMID- 8991597
TI  - [Transplacental transmission of the causative agent in experimental rickettsial
      infection].
AB  - It was shown in the experiments on the model of typhus infection in guinea-pigs
      that the pathogenic organism can be inherited by foetus from the mother's
      organism in the period of acute infection. It is confirmed by the presence of
      positive seroconversion in 86% of born offsprings and the character of the
      immunity response after the control infection that is the initial formation of
      immunoglobulins of form G (Ig G). At the same time there was no such a transfer
      of pathogenic organisms in 14% of offsprings. This fact is testified by the
      absence of seroconversion and the initial formation of immunoglobulins of form M
      (Ig M) with following formation of immunoglobulins of form G (Ig G) after control
      infection rickettsia Prowazekii.

PMID- 8991598
TI  - [Rarely encountered, atypical and new species of enterobacteria].
AB  - The article characterizes "rare", atypical and new individualized representatives
      of Enterobacteriaceae family. Classification approach is formulated which makes
      it possible to subdivide enterobacteria into three groups according to frequency
      of isolation, genetic determination and degree of atypicality. Schemes are
      presented for differential diagnosis for correct carrying out laboratory
      investigations and adequate interpretation of bacteriological assays results.

PMID- 8991600
TI  - 12th Congress of the Hungarian Society for Microbiology. Budapest, August 23-25,
      1995. Abstracts.

PMID- 8991599
TI  - American Thoracic Society--European Respiratory Society Longitudinal Data
      Analysis Workshop. Barcelona, Spain, September 21-23, 1995.

PMID- 8991601
TI  - [Treatment of 315 intracranial aneurysms using electrically controlled detachable
      coils].
AB  - The purpose of this study was to evaluate the results of 315 intracranial
      saccular aneurysms in 290 patients selectively treated with GDC in a single
      Center. One hundred and fifty eight patients were treated at the acute phase of
      the sub-arachnoid hemorrhage (SHA), sixty patients were treated more than three
      weeks after the SHA, seventy two patients were treated for unruptured aneurysms.
      We found at three months post-embolization good clinical results in 88,6%, a
      moderate disability in 3,4%, a severe disability in 2,7%, a 5,2% mortality. The
      complete aneurysm occlusion rate was 80,6% on the immediate control angiogram.
      Smaller the aneurysms, better were the anatomical results. The GDC treatment
      appears as an alternative treatment of surgery for the ruptured aneurysms at the
      acute-phase of SHA.

PMID- 8991602
TI  - [Vesicular flow in epithelial cells: physiopathologic importance of two
      multiligand receptors].
AB  - Epithelial structures lining the proximal tubule and the yolk sac are
      characterized by a high rate of internalization followed by degradation of the
      proteins exposed to their apical pole. This function implies the expression by
      these epithelia of specialized proteins which have the ability to bind numerous
      ligands and/or lysosomal targeting properties. An improved knowledge of these
      molecules is needed since their expression in a limited number of epithelia may
      account for the specificity of some pathologies induced in particular by toxins.
      This paper deals with two such "candidate" proteins, gp330/megalin and gp280
      which have been expressed in all species studied. gp280 is the target of
      teratogenic antibodies and is identified here as the receptor for intrinsic
      factor-cobalamin complexes but in all likelihood also binds other ligands.
      Antibodies to gp280 markedly stimulate the fusion of renal endosomes suggesting
      that it may play a role in targeting processes. gp330/megalin has been recently
      identified as the ligand of polybasic compounds such as gentamicin and is a key
      component in the internalization of the drug by tubular cells leading to renal
      toxicity. gp330/megalin also intervenes in endosomal fusion and some of its toxic
      properties may be mediated by this route.

PMID- 8991603
TI  - [AIDS: communication, information and prevention].

PMID- 8991604
TI  - [Hepatitis C].

PMID- 8991605
TI  - [Hepatitis C virus. Structure and genetic variability].
AB  - Infection by hepatitis C virus is characterized by a high rate of chronicity and
      low viremia. The virus has only been recently identified; it is a positively
      stranded RNA virus which shows homology in its genetic organisation with the
      Pestiviruses and Flaviviruses. There is not yet efficient culture system
      available. Several evidences indicate that the genetic variability of HCV genome
      might have important clinical implications; in particular infection by genotype
      1b is less responsive to interferon treatment and, possibly, associated to more
      severe liver diseases.

PMID- 8991606
TI  - [Biological diagnosis of hepatitic C virus infections].
AB  - Biological diagnosis of HCV infections consists of a two steps process. The first
      one is the detection, rarely induced by evocative symptoms, more often subsequent
      to systematic screenings. Third generation ELISA tests are used for this purpose
      on account of their high sensitivity. Their enhanced specificity, reaching 99.5%,
      still has to be checked using complementary tests, especially immunoblots assays.
      However, these methods may fail to detect specific antibodies during the acute
      phase of HCV infections or among immunodeficient patients, resulting in
      discrepancies or indeterminate conclusions. Then, the detection of HCV viremia by
      PCR is of great value to assert the diagnosis. The second step, before treatment,
      consists to identify the genotype and to determine the viral load by quantitation
      of the HCV RNA. Because the endemicity of HCV infections in France, these
      methods, although difficult an expansive, should be transferred to the medical
      laboratories, provided their quality and their accessibility will be preserved.

PMID- 8991607
TI  - [Epidemiology of infections linked to hepatitis C virus in France].
AB  - In France, the population of adult carriers of anti-HCV antibodies has been
      estimated about 600,000, but only 10 to 15% are aware of the diagnosis. Two major
      sources of infection have been identified : transfusion and intravenous drug use,
      accounting for 60% of HCV infections. In contrast, sexual or household
      transmission, mother-to-infant transmission or occupational exposure account for
      a small part of the HCV epidemic. In about 15% of cases, a nosocomial exposure is
      questioned, probably related to an insufficient decontamination of medical
      devices. Finally, no source of infection can be recognized in about 20% of
      infected patients. Among them, many have spent a long stay in high HCV prevalence
      areas, suggesting local percutaneous exposures. The diagnosis of chronic
      hepatitis C is often made late in the course of the disease, an average of 10
      years after exposure. At this time, a cirrhosis is present in about 20% of the
      patients. The frequency of cirrhosis depends on the duration of the HCV
      infection, and probably also on the source of transmission, independently of the
      duration of the disease. Thus, it has been observed that cirrhosis was more
      frequent in transfusion recipients than in intravenous drug users. Such a
      difference could be related to different HCV genotypes in the different groups at
      risk. The genotype 1b has been found predominant in transfusion recipients
      whereas genotype 3a was more frequent in drug users. Recently, a slight
      modification in the relative frequency of the different genotypes, mainly
      spreading and increased frequency of genotype 3a could lead to a modified
      epidemiology of HCV infection. The consequences of such modifications need to be
      evaluated.

PMID- 8991608
TI  - [Clinical picture and evolution of hepatitis C].
AB  - Hepatitis C is becoming the main cause of cirrhosis and primary liver carcinoma.
      Infection by hepatitis C virus (HCV) generally induces an asymptomatic acute
      hepatitis. HCV infection becomes chronic in about 80% of cases. In a minority of
      the subjects, chronic HCV infection is asymptomatic with persistent viremia and
      normal liver tests. These asymptomatic subjects have minimal liver histologic
      lesions and a good prognosis. In a majority of the subjects, chronic HCV
      infection is associated with chronic hepatitis with increased serum transaminases
      levels. Among the patients with chronic hepatitis, the majority have a mild liver
      disease with a moderate increase in serum transaminases levels and, at liver
      histology, minimal lesions; a minority (about 20%) have a more severe liver
      disease and will develop cirrhosis after 5 to 20 years. In patients with HCV
      related cirrhosis, the incidence of hepatocellular carcinoma is high (around 5%
      per year). The factors influencing the evolution of HCV infection are not known.
      Alcohol is certainly an important factor which increases the risk of development
      of fibrosis then cirrhosis. Virus related factors, such as genotype and level of
      replication, might also be important. Autoimmune diseases have been reported in
      association with hepatitis C. HCV infection is a major cause of mixed
      cryoglobulinemia associated with vasculitis or glomerulonephritis. A relationship
      between HCV and auto-immune diseases such as thyroiditis or Gougerot syndrome has
      been suggested but not demonstrated. HCV infection is frequent in patients with
      porphyria cutanea tarda; in these patients, HCV related liver disease might
      trigger the expression of the metabolic disease.

PMID- 8991609
TI  - [Prevention and treatment of hepatitis C].
AB  - Interferon is the only treatment shown to be effective on hepatitis C in
      controlled trials. The response to treatment is generally assessed in terms of a
      return to normal transaminase activity, but also negative PCR testing for viral
      RNA and histopathological examination of the liver. At a dose of 3 MU three times
      a week for 6 months, 25% of patients have a persistent return to normal
      transaminase activity, 25% relapse when interferon is withdrawn, and the
      remaining 50% have persistently high levels at the end of treatment and are
      considered resistant. The rate of persistent responses increases to 40% when
      treatment is extended to one year. Viral RNA becomes undetectable in the serum of
      80% of these responders. Most also have a histological improvement, but so do a
      number of patients who relapse or who are resistant. In the longer term,
      interferon could prevent the onset of liver cancer in patients with viral C
      cirrhosis. Interferon is generally well tolerated at the doses currently used,
      most side effects (hematologic, neuropsychiatric and thyroid disorders) resolving
      when treatment is stopped. The following factors are clearly predictive of the
      response to interferon : young age, short time since onset, absence of cirrhosis,
      lower-level viremia, and infection by HCV genotypes other than 1b. Interferon is
      markedly less effective in immunodeficient patients (transplant, HIV infection,
      etc.). Several add-on treatments have been tried, but ribavirin appears to be the
      most promising, both during initial interferon therapy and for patients who
      relapse or are resistant to a first course. Interferon therapy of the acute phase
      of hepatitis C significantly reduces the risk of chronic liver disease. There is
      no vaccine against HCV infection.

PMID- 8991610
TI  - [Eulogy of Jean Guilhon (1906-1995)].

PMID- 8991611
TI  - [Medicine facing the challenge of genetics: from singular workshop to public
      health].
AB  - Medical genetics has established itself as a new field of medicine over the past
      20 years. With its new techniques for artificial fertilisation, prenatal
      diagnosis and predictive medicine, it allows to control the quality of our
      children, raises the idealistic possibility of the perfect child, and already
      offers to predict the destiny of each of us. Going beyond the level of the
      individual in medicine, it implicates at the same time couples, families and
      indeed entire populations. It therefore provokes questions about the nature of
      man, his dignity and moral values. At this crucial point, it must have guides to
      prevent it becoming distanced from its essential vocation which is the medical
      treatment of human beings.

PMID- 8991612
TI  - [Tests for evaluating the effectiveness of pediculicides: importance and
      limitations].
AB  - The obligation to prove pediculicides efficacy is relatively recent. Two tests
      are required by the authorities to obtain registration. In vitro test (with
      Pediculus humanus humanus) is the first step to evaluate the efficacy of new
      molecules. It must be followed by bio-clinical tests (with infested children by
      Pediculus humanus capitis). For those tests the authors advise to respect the
      "three units rule": unit of time (no more than 2 days for the test), unit of
      place (same environment) and unit of action (only one team to apply and evaluate
      products). This type of tests is possible only in countries with high infestation
      (at least 60% of prevalence). A third test is consequently advised, the ex vivo
      test using Pediculus humanus capitis obtained from infested children in France.
      This test can be useful also to re-evaluate current products in the light of
      increased resistance or decreased sensitivity of the lice. Finally some other
      tests can be advised to prove some other activities like remanence or repellent
      properties or to estimated lice resistance.

PMID- 8991613
TI  - [Recent data on the epidemiology of Japanese encephalitis].
AB  - Japanese encephalitis is an arbovirosis the incidence and geographic distribution
      of which are increasing in rural areas of tropical and temperate Asia. A total of
      about 45,000 to 50,000 clinical cases occur annually. The Flavivirus responsible
      for the disease shows birds as usual hosts, and Culex mosquitoes as vectors.
      After a first amplification cycle in birds, the virus can be transmitted to
      domestic pigs, then to man. This scheme, however, shows large variations in the
      different regions, according to the climate which determines the dynamics of
      mosquito and bird populations, and to the ways of life of human populations,
      particularly for the rice-growing technics and pig breeding. The epidemiologists
      schematically distinguish tropical endemic areas, subtropical endemic-epidemic
      zones, and temperate epidemic zones. However, our knowledge on the epidemiology
      of Japanese encephalitis carries many incompletely understood aspects, for
      instance the reasons of the actual geographic distribution of the disease, or the
      mechanisms for persistence of the virus between epidemics. Furthermore, these
      epidemiological situations are changing with time, particularly with the
      development of the new agrosystems linked with demographic increase, while recent
      technics of genomic analysis allow the recognition of several viral genotypes.
      The prevention of Japanese encephalitis presently involves vector control,
      vaccination and, in some cases, particular modifications of environment. Each of
      these measures shows proper logistic, technical or financial difficulties, which
      often prevent their generalized use. However, one can observe that, in the
      countries where vaccination is systematically carried out, the incidence of the
      disease seems considerably decreasing, while elsewhere it shows a tendency to
      increase. The main difficulties lie in the high cost of the vaccine and in the
      weight of immunization scheme, which make uneasy its integration in the Expanded
      Vaccination Programme. For these reasons, the virologists are looking for other
      vaccine types, particularly recombinant vaccines relying on obtaining, by
      genetical manipulation, envelop proteins with protection effect. Finally, remains
      the question of immunization of travellers and expatriate people. It seems
      desirable to recommand this vaccine only to the really exposed persons; this
      means persons performing a rather long stay in a rural area of an endemo-epidemic
      region, or during the season of transmission in an epidemic region. However, the
      risk cannot be completely absent, and it is necessary to draw attention to other
      methods aiming at decreasing man-vector contact.

PMID- 8991615
TI  - [The surgical experience].
AB  - A fifteen years long multidisciplinary medico-surgical approach concerning more
      than 160 transsexual patients is reported. A very steady initial period, at least
      two years long, was observed before any therapeutic decision, concerning
      psychiatric, endocrinologic and surgical aspects. All patients were treated on
      behalf of the national medical board (Conseil de l'Ordre) and with the financial
      support of the national health service (Securite sociale) in public practice. The
      main conclusions of this study are summarized by Pr. J.P. Luton, endocrinologist,
      Pr. J. Breton, psychiatrist and Pr. P. Banzet, plastic surgeon.

PMID- 8991614
TI  - [Psychiatric aspects of transsexualism].
AB  - Transsexualism is a mental disease in which gender identity goes contrary to
      corporal reality. Diagnostic is purely clinical and needs a prolonged
      observation. The actual experience concerning about 700 cases allow us to
      consider that one quarter of patients should get sexual conversion.

PMID- 8991616
TI  - [The place of endocrinology in the management of transsexualism].
AB  - Transsexualism is not a sexual perversion but rather a gender identity disorder.
      The patient claim for his personal and public image and condition. The diagnosis
      problems arise from the lack of clinical, biological or hormonal typical signs.
      The pathogenesis is unclear but works in progress suggest somatic alterations.
      These alterations might be pre or perinatal hormonal changes and/or alterations
      in cerebral structures involved in sexual differentiation. Transsexualism is not
      a treatable disease using currently available treatments. Only hormonal and
      surgical treatments with sex reassignment might answer to the patient's request
      and improve his mental condition. Hormonal treatment might only prescribed after
      a consensus statement of about the sex reassignment of the patient and under
      medical follow-up. An early and strict medical follow-up of the patients by a
      multi specialist medical team is required and have to warrant the etic aspects.
      This is mostly important for the approval for sex reassignment from the
      authorities.

PMID- 8991617
TI  - [Bovine spongiform encephalopathy. Second update of data collected since the
      report of February 6, 1996].
AB  - The observation in 1995 and 1996 of 12 cases of a new variant of Creutzfeldt
      Jakob disease (V-CJD) in U.K. suggested a possible relation between this human
      cases and bovine spongiform encephalopathy (BSE). Recent papers about this topic
      are reviewed: BSE transmission to macaques, transmission of scrapie with embryo
      transfer, incidence of maternal transmission, PrP protein released by platelets,
      diagnostic test by detection of PrP protein in tissues of sheep, epidemiology of
      BSE, french regulations, identification of cattle in U.K.

PMID- 8991618
TI  - [Application of three-dimensional computer graphics in oncology].
AB  - Accurate 3D tumoral volume evaluation is now possible through the combined use
      and progress of computer graphics technics (3D reconstruction and visualization)
      and medical imagery (helicoidal TDM scanner). Specific organ and pathology
      oriented softwares can help answer rapidly to problems posed by oncologic
      praticians. A new decision support for diagnosis, therapy and follow-up is
      emerging. First results in liver tumors and hepatic regeneration macroscopic
      biometrics are presented. Tumoral or organ volumic index will be usable in the
      follow-up. TNM staging, external conformal radiotherapy for prostatic or brain
      tumors, drugs cytolytic effects evaluation will take great advantage of these
      technologies. 3D visualization and matching CT and MRI imagery can help computed
      assisted surgery.

PMID- 8991619
TI  - [Training and qualification of surgeons and surgical specialists in video
      endoscopic surgery].

PMID- 8991620
TI  - [Epidemiology of HIV infection, demographic consequences and impact on the
      politics of health in Sub-Saharan Africa].

PMID- 8991621
TI  - [The epidemic due to human immunodeficiency virus in the Pacific-Asian region].

PMID- 8991622
TI  - [Prevention of violence among adolescents and children].

PMID- 8991623
TI  - [Education for emergencies (Emergency medical aid and catastrophic medicine)].

PMID- 8991624
TI  - Six months' experience with a pharmacist-run Helicobacter pylori treatment
      clinic.

PMID- 8991625
TI  - Normal range estimation for repeated immunologic measures.
AB  - A method for estimating a normal range from a set of immunologic measurements on
      control subjects when there may be more than one observation per subject is
      described. The method is nonparametric, makes efficient use of all observations,
      and is very simple to apply. It is illustrated on a set of 152 CD38 measurements
      from 58 healthy men.

PMID- 8991626
TI  - Celiac disease and hypoparathyroidism: cross-reaction of endomysial antibodies
      with parathyroid tissue.
AB  - Celiac disease (CD) is a gluten-sensitive enteropathy characterized by the
      presence of serum antibodies to endomysial reticulin and gliadin antigens. CD has
      been associated with various autoimmune endocrine disorders, such as diabetes. We
      report a rare case of idiopathic hypoparathyroidism with coexistent CD
      characterized by the presence of serum autoantibodies. Studies were conducted to
      determine the specificities of these autoantibodies and to localize the antibody
      binding sites by indirect immunofluorescence and immunoelectron microscopy. Sera
      from a patient with idiopathic hypoparathyroidism and CD and from two patients
      with CD alone were tested by indirect immunofluorescence for autoantibodies to
      parathyroid and endomysial antigens. The specificities of the antibody reactions
      were determined by testing the sera before and after absorption with monkey
      stomach tissue. In addition, immunoelectron microscopic studies were performed to
      determine the localization of the endomysial antigen. Indirect-immunofluorescence
      studies on the patient's serum were positive with the parathyroid as well as the
      endomysial substrate. Similar reactions were also observed with the sera of
      endomysial antibody-positive patients with CD. Absorption of the sera with monkey
      stomach powder, which is known to have the endomysial antigen, abolished the
      antibody activities on both the endomysial substrate and the parathyroid tissue.
      Immunoelectron microscopic studies showed that endomysial antibody activity was
      associated with antigens localized on the myocyte plasma membrane and in the
      intercellular spaces. Thus, reactions of the patient's serum with the parathyroid
      tissue were due to endomysial antibodies and were not parathyroid specific as in
      patients with idiopathic hypoparathyroidism who did not have coexistent CD. In
      conclusion, indirect-immunofluorescence tests on parathyroid tissue detect not
      only tissue-specific antibodies but also cross-reactive antibodies, and this
      should be taken into consideration when these tests are performed.

PMID- 8991627
TI  - Evaluation of serological assays for identification of parvovirus B19
      immunoglobulin M.
AB  - Three different enzyme immunoassays (EIAs) (Parvoscan-B19, IBL parvovirus B19,
      and IDEIA parvovirus B19) and one immunofluorescence assay (Biotrin Parvo B19
      IFA) were evaluated for detection of parvovirus B19 immunoglobulin M (IgM)
      antibodies in 203 clinical serum samples. An IgM antibody capture
      radioimmunoassay was used as a reference test. Serum specimens obtained from
      patients with clinical symptoms suggestive of parvovirus B19 infections were used
      to evaluate the sensitivities of the assays, which were shown to be comparable
      for the Biotrin IFA and IDEIA (97%) and lower for the other two EIAs (90%). In
      order to test the specificity of the assays, clinical serum samples with IgM
      antibodies against other viruses were examined, as well as sera with rheumatoid
      factor activity and sera from healthy pregnant women. The specificities of B19
      IgM antibody detection were 96% for the Biotrin IFA, 96% for IDEIA, 90% for
      Parvoscan, and 88% for the IBL assay. These results show that all four assays can
      be recommended for diagnostic purposes, although false-positive results may be
      seen with other acute viral infections, healthy pregnant women, and rheumatoid
      factor-positive samples.

PMID- 8991628
TI  - Expression of the somatostatin gene in human astrocytoma cell lines.
AB  - Somatostatin (somatotropin release-inhibiting hormone; SRIH) has been
      demonstrated in neurons of the central nervous system (CNS) as well as in
      endocrine cells of the pancreas and gastrointestinal tract and can suppress
      various immune functions including lymphocyte proliferation, immunoglobulin
      synthesis, and cytokine production. Since astrocytes possess antigen-presenting
      activity and can secrete a wide array of immunoregulatory and inflammatory
      cytokines, we studied SRIH gene expression in both astrocyte cell lines and
      mitogen-stimulated peripheral blood mononuclear leukocytes from healthy donors.
      We now report by means of a complementary DNA-based reverse transcription PCR
      that differential levels of SRIH mRNA were expressed in 9 of 11 human astrocytoma
      cell lines tested but were undetectable in activated peripheral blood mononuclear
      leukocytes as well as in a variety of human lymphocyte and monocyte cell lines.
      The synthesis and secretion of SRIH protein by astrocytoma cells that expressed
      SRIH transcripts were confirmed by specific radioimmunoassay of cell culture
      fluids. These findings support the notion that SRIH gene expression occurs in
      human astrocytoma cells but not in mature lymphoid cells of the immune system.

PMID- 8991630
TI  - Silicate antibodies in women with silicone breast implants: development of an
      assay for detection of humoral immunity.
AB  - Silicon, in the form of sodium silicate (Na2SiO3), adsorbed onto bovine serum
      albumin (BSA)-precoated plates served as the solid-phase antigen in an enzyme
      immunoassay to detect silicate-reactive antibodies in the plasma of 40
      symptomatic women with silicone breast implants, 91 asymptomatic women with
      silicone breast implants, 50 healthy control women, and 52 women with rheumatic
      diseases and without silicone breast implants, Silicate-reactive antibodies of
      immunoglobulin G (IgG) or IgM isotypes were detected in the plasma of 30% (12 of
      40) of the symptomatic women with silicone breast implants; 9% (8 of 91) of the
      asymptomatic women with silicone breast implants; 5% (1 of 20) of the women
      without implants who had systemic lupus erythematosus; and 0% (0 of 32) of the
      women without implants who had either Sjogren syndrome, scleroderma, or
      rheumatoid arthritis. Only 2% (1 of 50) of the sera from the healthy control
      women contained silicate-reactive antibodies. Preincubation of sera with silicate
      and eight other metal compounds (including SiO2) demonstrated that the IgG and
      IgM antibodies bound specifically to silicate, because preincubation with Na2SiO3
      inhibited more than 90% of the activity, whereas CrO3, Li2SO4, MgSO4, NiSO4,
      HgCl2, ZrOCl2, BeSO4, and SiO2 failed to inhibit the IgG or IgM antibody binding
      to the silicate-BSA plates. Furthermore, the F(ab')2 portion and not the Fc
      portion of the silicate-reactive IgG was reactive with BSA-bound silicate in the
      enzyme immunoassay. The assay for silicate-reactive antibodies was quantified by
      assigning arbitrary units to a standard curve composed of serial twofold
      dilutions of high-positive (ten times higher than the cutoff) silicate antibody
      sera. This novel assay is a useful method for detecting and quantifying humoral
      immune response to silicate.

PMID- 8991629
TI  - Phenotype of lymphocytes associated with the inflammatory reaction to silicone
      gel breast implants.
AB  - The tissue response to silicone gel breast implants typically includes an
      inflammatory infiltrate that consists of macrophages, foreign body-type giant
      cells, and a variable number of lymphocytes and plasma cells. The phenotype of
      the lymphocytic component was investigated with three-color flow cytometry.
      Lymphocytes were obtained by collecting fluid from the space between the implant
      and the fibrous capsule or by washing cells from the fibrous capsule at the time
      of implant removal with total capsulectomy. Eighty-nine percent of the implant
      associated lymphocytes were T cells. Twenty-five percent of the CD3+ T cells
      coexpressed HLA-DR compared with only 7.9% of matched peripheral blood
      lymphocytes. Sixty-eight percent of the implant-associated T cells coexpressed
      CD4 and CD29, while only 3% of the T cells coexpressed CD4 and CD45RO. The
      expression of HLA-DR and the predominance of CD29+ CD4+ T cells indicate that
      there is immune activation with the potential for stimulating antigen-specific
      antibody production. The role of silicone gel breast implants in immune
      activation and its clinical significance require further investigation.

PMID- 8991631
TI  - An indirect double-antibody sandwich enzyme-linked immunosorbent assay (ELISA)
      using baculovirus-expressed antigen for the detection of antibodies to
      glycoprotein E of pseudorabies virus and comparison of the method with blocking
      ELISAs.
AB  - Antibodies in porcine sera against glycoprotein E (gE) of pseudorabies virus
      (PRV) are usually measured in blocking enzyme-linked immunosorbent assays
      (ELISAs) with one or two murine monoclonal antibodies (MAbs) directed against gE.
      Our aim was to develop a confirmation assay which is based on another principle
      and which is able to detect antibodies directed against most potential binding
      sites on gE with high specificity. Therefore, we developed an indirect double
      antibody sandwich assay (IDAS) using recombinant gE expressed by baculovirus
      (BacgE960). A fragment of the gE gene consisting of nucleotide positions +60 to
      +1020 of gE, coding for the major antigenic sites of gE but not the transmembrane
      region, was cloned behind the signal sequence of PRV gG and the p10 promoter in a
      baculovirus vector. Immunoblot analysis showed that the expressed protein reacted
      with MAbs directed against five of the six antigenic sites on gE. Although the
      conformation of some antigenic sites, notably antigenic sites E and C, was not
      identical to their natural conformation, the expressed protein bound gE-specific
      antibodies in porcine sera in Western blots (immunoblots) and ELISAs. For the
      IDAS, a coating MAb directed against the nonimmunodominant antigenic site A on gE
      was chosen. A major obstacle in binding ELISAs, such as the IDAS, appeared to be
      the high nonspecific binding activity observed in porcine sera. As a result, sera
      could be tested only in relatively high dilutions in the BacgE960 IDAS, in
      contrast to the testing of sera in blocking ELISAs. The sensitivity and
      specificity of the newly developed BacgE960 IDAS were evaluated and compared with
      those of five commercially available blocking ELISAs by using several sets of
      sera of known PRV disease history. The BacgE960 IDAS assay had a high diagnostic
      specificity and a moderate sensitivity. The five blocking ELISAs differed
      remarkably in sensitivity and specificity, thereby illustrating the need for
      standardization and confirmation. We conclude that the BacgE960 IDAS is a useful
      and specific additional (confirmatory) test for the detection of antibodies to
      gE.

PMID- 8991632
TI  - Circulating complement proteins in patients with sepsis or systemic inflammatory
      response syndrome.
AB  - The systemic inflammatory response of the body to invading microorganisms, termed
      sepsis, leads to profound activation of the complement system. Pathophysiological
      concepts suggest that complement activation occurs very early in this syndrome.
      Thus, we discuss whether the determination of concentrations of the complement
      components C3a, C5a, and C3 in plasma as well as of the C3a/C3 ratio might be
      helpful to diagnose sepsis early. For this purpose, 33 patients from an intensive
      care unit were monitored for 10 days. In comparison with healthy donors, C3a
      levels and the C3a/C3 ratio of intensive-care-unit patients were significantly
      elevated (P < 0.0001) on admission. In contrast, C3 levels were significantly
      reduced (P < 0.0001) but increased during the study. C5a levels in the plasma of
      healthy donors and patients were identical. Twenty-two of 33 patients fulfilled
      microbiological and clinical criteria of sepsis. Eleven patients had signs of
      systemic inflammatory response syndrome but no microbiological evidence of
      sepsis. The groups could be differentiated from each other by their C3a levels or
      their C3a/C3 ratios during the first 24 h after the clinical onset of sepsis (P <
      0.05). Septic patients in shock had higher C3a levels than normotensive septic
      patients, although the differences were not significant. Nonsurvivors had
      significantly higher C3a levels on admission than survivors (P = 0.0185). No
      differences were found between septic patients who developed adult respiratory
      distress syndrome and those who did not. Thus, determination of C3a
      concentrations in plasma may prove useful (i) to diagnose sepsis early, (ii) to
      differentiate between patients with sepsis and those with systemic inflammatory
      response syndrome, and (iii) to assess prognosis.

PMID- 8991634
TI  - Alterations in lymphocyte phenotype and function in children with shigellosis who
      develop complications.
AB  - This study was designed to see whether alterations occur in peripheral blood
      mononuclear cell phenotype and function in children with Shigella dysenteriae 1
      infection with complications (leukemoid reaction and/or hemolytic-uremic
      syndrome) and whether there are any alterations prior to the development of
      complications. The following groups of children (ages, 12 to 60 months) were
      compared: children without any infection (n = 51), children with uncomplicated
      shigellosis (n = 65), children admitted with complicated shigellosis (leukemoid
      reaction and/or hemolytic-uremic syndrome) (n = 29), and children with
      shigellosis who developed complications after enrollment (subsequently
      complicated shigellosis) (n = 12). Tests for the peripheral blood mononuclear
      cell phenotype (CD3, CD4, CD8, CD57 [corrected], CD20, and CD25), spontaneous
      proliferation, and the proliferative response to phytohemagglutinin, pokeweed
      mitogen, and the lipopolysaccharide of S. dysenteriae 1 were performed, as were
      skin tests for delayed-type hypersensitivity (DTH). Children who subsequently
      developed complications differed from other groups of children as follows: (i)
      the numbers of CD3+ and CD4+ cells were lower than in uninfected children (P <
      0.05), (ii) the CD4/CD8 ratio was lower than in children with uncomplicated
      shigellosis (P < 0.05) and in uninfected children (P < 0.05), and (iii) the
      levels of spontaneous proliferation of peripheral blood mononuclear cells were
      higher and DTH responses were lower than those in children with uncomplicated
      shigellosis (P < 0.05 and P < 0.017, respectively). Children with complications
      differed by having (i) increased numbers of CD3- CD57- [corrected] CD20- cells (P
      < 0.05) compared with those in other groups of children and (ii) lower CD4/CD8
      ratios (P < 0.05), higher levels of spontaneous proliferation (P < 0.05), and
      lower DTH responses (P = 0.005) than children with uncomplicated shigellosis.
      Three to five days after enrollment, the number of CD4+ cells increased in
      children who subsequently developed complications (P = 0.025), i.e., when they
      developed complications and at this time their CD4+ cell number was similar to
      that of other groups of children. Thus, lymphocyte phenotype and function are
      altered prior to the development of complications in children with shigellosis,
      and once complications develop, the pattern of alterations changes. Whether these
      alterations have a role in precipitating complications or whether they reflect
      early events underlying the development of complications remains to be
      elucidated.

PMID- 8991633
TI  - Detection of anti-Borrelia burgdorferi antibody responses with the borreliacidal
      antibody test, indirect fluorescent-antibody assay performed by flow cytometry,
      and western immunoblotting.
AB  - Borreliacidal antibodies participate in the resolution of Lyme disease by
      clearing Borrelia burgdorferi sensu lato from the host. Detection of
      borreliacidal antibodies is also valuable for determination of the specific
      serodiagnosis of Lyme disease. We show in this work that antibody detected by the
      borreliacidal antibody test did not correlate with antibody detected by the
      indirect fluorescent-antibody assay or Western immunoblotting. Detection of
      borreliacidal antibody decreased with elimination of the spirochete from the host
      in the presence or absence of therapy. By contrast, the antibody responses
      detected by the indirect fluorescent-antibody assay or Western immunoblotting
      remained elevated or continued to expand, respectively. This suggests that the
      borreliacidal antibody test is a prognostic indicator for clearance of the
      spirochete. Additional investigations with humans are needed to confirm the
      prognostic potential of the borreliacidal antibody test.

PMID- 8991635
TI  - (1-->3) beta-D-glucan as a quantitative serological marker for Pneumocystis
      carinii pneumonia.
AB  - We detected (1 --> 3) beta-D-glucan (beta-glucan), which is one of the major
      components of the cyst wall of Pneumocystis carinii, in sera obtained from
      patients with P. carinii pneumonia (PCP). We confirmed that beta-glucan was
      detectable by a beta-glucan detection kit (G test; Seikagaku Corporation) in
      bronchoalveolar lavage fluids (BALFs). The mean concentration of beta-glucan in
      BALFs obtained from specific-pathogen-free nude mice infected with P. carinii (n
      = 7; mean, 2,631 [range, 1,031 to 9,095] pg/ml) was significantly higher (P <
      0.001) than that in uninfected, specific-pathogen-free mice (n = 7; 6.5 [range,
      4.0 to 8.3] pg/ml). The mean level of beta-glucan in BALFs from PCP patients was
      significantly higher (P < 0.05) than that in BALFs from patients with other lung
      diseases (7,268 [range, 1,355 to 15,500] pg/ml [n = 4] versus 242.5 [17 to 615]
      pg/ml [n = 4]). In sera from six of seven patients with PCP, significant levels
      of beta-glucan (494.1 [8.5 to 1,135] pg/ml) were detected, while it was
      undetectable in patients with other lung diseases and in a control group. In five
      patients at follow-up, the level of beta-glucan decreased with clinical
      improvement. These results suggest that beta-glucan is detectable in sera from
      patients with PCP and it is a practical serological marker for monitoring of the
      disease during treatment.

PMID- 8991636
TI  - Diagnostic value of the indirect immunofluorescence assay in cat scratch disease
      with Bartonella henselae and Afipia felis antigens.
AB  - Serum samples from 35 cat scratch disease (CSD) patients, 180 control patients
      (123 without lymph node enlargement and 57 with lymph node enlargement not
      evoking CSD), and 102 nonpatient subjects (35 with cat contact and 67 without cat
      contact) were tested by semiquantitative indirect immunofluorescence assay for
      the presence of antibodies directed to Afipia felis (ATCC 53690T) or Bartonella
      henselae (ATCC 49882T). The CSD group had statistically higher antibody titers
      against B. henselae than the control groups (P < 10(-5)), whereas no difference
      in A. felis antibody titers was evidenced among all groups tested. Among the 317
      serum samples studied, the three with high A. felis antibody titers ( > or = 64)
      also had high antibody titers against other alpha-2 proteobacteria. The value of
      the indirect immunofluorescence assay with B. henselae antigen for the diagnosis
      of CSD was as follows: for a cutoff of 32, sensitivity was 0.80, specificity was
      0.85, and the likelihood ratio was 5.1; for a cutoff of 64, the likelihood ratio
      was 12.1. In summary, in France, CSD is associated with high antibody titers
      against B. henselae, as previously described in the United States. However, the
      causes for B. henselae seronegativity in CSD patients and those for high antibody
      titers outside the typical nosological frame of CSD still have to be identified.

PMID- 8991637
TI  - T-cell proliferative response to human papillomavirus type 16 peptides:
      relationship to cervical intraepithelial neoplasia.
AB  - The incidence of human papillomavirus (HPV)-related cervical intraepithelial
      neoplasia (CIN) and cervical cancer is increased with immunodeficiency, but the
      role of immune response, including cell-mediated immunity, in disease prevention
      is not well understood. In this study, T-cell proliferative responses to six
      synthetic peptides with predicted immunogenic determinants from the HPV-16 E4,
      E6, E7, and L1 open reading frames were analyzed in 22 sexually active women with
      new-onset CIN and 65 sexually active women without cervical disease,
      characterized by cytology, colposcopy, and HPV testing. T-cell proliferative
      responses were demonstrated to all six HPV-16 peptides. Although not
      statistically significant, rates of reactivity to E6 (24-45) were higher among
      sexually active women without disease (26%) than among women with current CIN
      (7%), as was the overall number of peptides stimulating a response. Women with
      CIN may not respond to selected HPV antigens as well as women without disease do.

PMID- 8991638
TI  - Immunoglobulin G avidity testing in serum and cerebrospinal fluid for analysis of
      measles virus infection.
AB  - We studied a variety of patients with measles virus infection by using avidity
      testing for measles virus-specific immunoglobulin G (IgG) in serum and
      cerebrospinal fluid samples. For the avidity testing, an Enzygnost measles IgG
      enzyme-linked immunosorbent assay kit was used with an 8 M urea denaturing
      method. With this method, low-avidity IgG (acute primary infection, avidity of <
      30% within 15 days of the onset of rash) and high-avidity IgG (subacute
      sclerosing panencephalitis, avidity of > 75%) could be clearly distinguished by
      using serum samples. One patient, who developed a typical course of measles
      despite a previous vaccination, showed a positive IgM response with an initial
      low titer of measles virus-specific IgG of low avidity, but a later sample
      revealed a high titer of IgG of intermediate (40%) avidity, suggesting previous
      immunological priming. Two patients with breakthrough infection (secondary
      vaccine failure), both having central nervous system involvement, showed a
      positive IgM response with initial high titers of serum IgG of high avidity. In
      addition, one of the patients had a detectable level of measles-specific IgG in
      cerebrospinal fluid. In this patient, the avidity of both serum and cerebrospinal
      fluid IgG decreased during the short follow-up period. This phenomenon has never
      before been reported. In subacute sclerosing panencephalitis patients, the
      avidity of cerebrospinal fluid IgG was consistently lower than that of serum IgG.
      The difference in avidity between cerebrospinal fluid and serum IgG may be used
      as a direct indicator of intrathecal production of IgG. In conclusion, the
      avidity testing is simple to perform, reliable, and highly informative in the
      analysis of measles virus infection.

PMID- 8991639
TI  - Detection of rubella virus-specific immunoglobulin M antibodies with a
      baculovirus-expressed E1 protein.
AB  - The structural proteins of rubella virus (RV) were expressed in insect cells by
      using the baculovirus expression vector system. The recombinant E1 envelope
      glycoprotein was purified by immunoaffinity chromatography and used to detect RV
      specific immunoglobulin M antibodies in a time-resolved fluoroimmunoassay.
      Correlation analysis between the reactivities of antibodies against this
      recombinant E1 and the reactivities against authentic RV antigen shows that
      purified E1 can detect RV antibodies of the immunoglobulin M type.

PMID- 8991640
TI  - Specific antibody response to oligomannosidic epitopes in Crohn's disease.
AB  - Elevated antibody levels against the yeast Saccharomyces cerevisiae have been
      reported in sera from patients with Crohn's disease and not with ulcerative
      colitis. The aim of the study was to identify the nature of the epitopes
      supporting this antibody response. Whole cells from different S. cerevisiae
      strains were selected in immunofluorescence assay for their ability to
      differentiate the antibody responses of patients with Crohn's disease and
      ulcerative colitis. Their cell wall phosphopeptidomannans were then tested as
      antigen in enzyme-linked immunosorbent assay (ELISA) against sera from 42
      patients with Crohn's disease, 20 patients with ulcerative colitis, and 34
      healthy controls. Graded chemical degradations were performed on the most
      reactive strain phosphopeptidomannan. The discriminating epitope was determined
      through gas-liquid chromatography-mass spectrometry. The greatest discrimination
      among patients with Crohn's disease, ulcerative colitis, and controls was
      obtained with Su1, a S. cerevisiae strain used in brewing of beer. ELISA directed
      against phosphopeptidomannan of this strain was 64% sensitive and 77% specific
      for discriminating Crohn's disease versus ulcerative colitis and 71% sensitive
      and 89% specific for Crohn's disease versus controls. Periodate oxidation and
      selective degradation demonstrated that the most important polysaccharide epitope
      was shared by both the acid-stable and the alkali-labile domains of the
      phosphopeptidomannan. The determination of oligomannose sequences of S.
      cerevisiae Su1 phosphopeptidomannans suggested that a mannotetraose, Man (1 -->
      3)Man(1 --> 2)Man(1 --> 2)Man, supported the serological response seen in Crohn's
      disease. Further identification of the immunogen eliciting this antibody response
      as a marker of the disease may help to understand its etiology.

PMID- 8991642
TI  - Antibody against human immunodeficiency virus type 1 (HIV-1) Tat protein may have
      influenced the progression of AIDS in HIV-1-infected hemophiliac patients.
AB  - Retrospective analysis of serum samples from a group of hemophiliac patients who
      became infected with human immunodeficiency virus type 1 (HIV-1) between 1984 and
      1985 has shown that, at variance with other HIV-1-infected patients, at the
      onset, or at least at a very early phase of HIV-1 infection, they constantly have
      elevated levels of antibodies against HIV-1-transactivating Tat protein and an
      absent or barely detectable p24 antigenemia. Anti-Tat antibodies in initial serum
      samples from hemophiliac patients were probably the consequence of the passive
      administration of immunoglobulins present in low- or intermediate-purity clotting
      factor concentrates prepared from HIV-1-infected blood. Furthermore, the analysis
      of serial serum samples obtained during the course of the disease, in which
      passively acquired anti-Tat antibodies were substituted by actively produced
      antibodies, demonstrated an inverse relationship between anti-Tat antibody and
      p24 anti-genemia levels throughout the observation period. These data seem to
      suggest that anti-Tat antibody may have some influence on the course of HIV-1
      infection.

PMID- 8991641
TI  - Purification and seroreactivity of pneumococcal surface adhesin A (PsaA).
AB  - Pneumococcal surface adhesin A (PsaA) is a 37-kDa common protein antigen of
      Streptococcus pneumoniae. In the present study, the protein was purified so that
      its immunoreactivity could be determined. PsaA was released and purified from
      cells by lysis in the presence of n-laurylsarcosine; this was followed by
      ammonium sulfate precipitation and subsequent preparative isoelectric focusing. A
      capture antibody enzyme-linked immunosorbent assay was used to determine the
      immunoreactivity of purified PsaA. The assay had a 67% sensitivity for sera from
      patients with bacteremic pneumococcal pneumonia. A specificity of 97% was
      estimated on the basis of a lack of reactivity with sera from patients with
      pneumonia caused by other organisms. PsaA is a potential vaccine candidate and
      may be useful as an antigen in a diagnostic assay for pneumococcal disease.

PMID- 8991643
TI  - Release of soluble tumor necrosis factor receptors in Mediterranean spotted fever
      rickettsiosis.
AB  - Tumor necrosis factor alpha (TNF) is a key cytokine in the defense against many
      intracellular pathogens, including Rickettsia conorii, the causative agent of
      Mediterranean spotted fever (MSF). The levels of two soluble TNF receptors (sTNFR
      p55 and sTNFR-p75), the extracellular domains of the two cell surface receptors
      for TNF, were elevated in the acute-stage plasma samples from 20 patients with
      serologically confirmed MSF. The median values were 3.1 and 7.8 ng/ml for sTNFR
      p55 and sTNFR-p75, respectively. sTNFR values correlated significantly with
      plasma TNF concentrations. Patients with severe MSF had higher values for both
      receptor fragments than patients with nonsevere disease. The differences were
      statistically significant for sTNFR-p55 (median, 5.8 versus 2.0 ng/ml; P =
      0.008). Given the proportionately higher values for both TNF and sTNFR-p55 in
      patients with severe MSF, the sTNFR-p55/TNF ratios for the two patient subgroups
      did not differ (P = 0.5), while the sTNFR-p75/TNF ratios were significantly
      different (P = 0.01), with disproportionately lower values in patients with
      severe disease.

PMID- 8991644
TI  - Antibody response to human parvovirus B19 in patients with primary infection by
      immunoblot assay with recombinant proteins.
AB  - Human parvovirus B19 recombinant VP1 and VP2 capsid proteins were produced by a
      procaryotic pGEX expression plasmid to evaluate the humoral response by
      immunoblot assay in 14 patients with primary infection. The same concentrations
      of VP1 and VP2 recombinant proteins were used. This demonstrates that VP1
      immunoglobulin M detection and/or VP1 immunoglobulin G seroconversion is a
      reliable marker of primary infections. Consequently, detection of antibodies to
      B19 VP1 might be helpful for identifying patients at risk for chronic B19
      infection or patients who are susceptible to viral reinfection.

PMID- 8991646
TI  - Antibody response of monkeys to invasion plasmid antigen D after infection with
      Shigella spp.
AB  - The antigen preparation most often used for determining the levels of antibodies
      to virulence-associated proteins of Shigella spp. consists of a mixture of
      proteins (including IpaB, IpaC, IpaD, and VirG*) extracted from virulent
      shigellae with water (water extract). To overcome the lack of specificity for
      individual antigens in the water-extract enzyme-linked immunosorbent assay
      (ELISA), the ipaD gene from S. flexneri has been cloned, expressed to a high
      level, and purified for use in a new ELISA for the determination of the levels of
      antibody against IpaD in monkeys and humans challenged with shigellae. The IpaD
      ELISA for serum immunoglobulins G and A correlated well with the water-extract
      ELISA in that monkeys infected with S. flexneri or S. sonnei responded with high
      serum antibody titers in both assays. The IpaD assay required less antigen per
      well, had much lower background levels, and did not require correction with
      antigens from an avirulent organism. In conjunction with the water-extract ELISA,
      it was possible to identify infected animals that did not respond to IpaD but did
      produce antibodies that reacted in the water-extract ELISA. This indicates that
      even though IpaB, IpaC, and IpaD are essential for the invasiveness phenotype,
      the infected host does not always produce antibodies against all components of
      the invasiveness apparatus.

PMID- 8991645
TI  - Immunological characterization of a recombinant 27-kilodalton antigenic protein
      from Paracoccidioides brasiliensis.
AB  - We report the expression in Escherichia coli of a 27-kDa antigenic protein from
      Paracoccidioides brasiliensis. When analyzed by immunoblotting, this recombinant
      antigenic protein was recognized by antibodies present in the sera of 40 of the
      44 paracoccidioidomycosis patients studied. No cross-reactions were observed with
      sera from patients with other mycoses (histoplasmosis, aspergillosis,
      cryptococcosis, sporotrichosis, and chromoblastomycosis) or with tuberculosis.

PMID- 8991647
TI  - [Section 218].

PMID- 8991648
TI  - [Meconium aspiration syndrome].
AB  - Meconium aspiration syndrome (MAS) is found in 0.2-6 per 1000 lifeborn neonates.
      Aspiration of meconium particles may occur before, during or after delivery,
      associated with deep inspiratory movements due to fetal depression. Aspiration of
      meconium may cause mechanical obstruction of the airways, chemical pneumonitis,
      and surfactant inactivation. The disease is commonly associated with the
      development of pulmonary hypertension and severe respiratory insufficiency. MAS
      may be prevented, at least in some infants, by appropriate suctioning at birth.
      Great progress has been made in the treatment: early administration of surfactant
      improves gas exchange in many neonates. High frequency oscillatory ventilation,
      NO-inhalation and extracorporal membrane oxygenation have a role in severe
      respiratory failure.

PMID- 8991650
TI  - [Report of experiences in psychological consultation in a gynecologic clinic].
AB  - Potential and limits of psychotherapeutic practice in a general hospital. It is a
      known fact that psychological care of women in general hospitals is limited. The
      limits are defined by the way hospitals are run and the way people interact. In
      fact, psychological and medical treatment should be considered equally effective
      tools for achieving optimum results. However, the old boundaries are falling and
      the system is changing. Whenever people come together, with their different views
      of reality and different ideas of how best to cope with it, there is a potential
      for discussion. In the hospital context, these different viewpoints often clash.
      In spite of these limitations, psychological practice in a hospital is often not
      only feasible, but necessary. It is often effective in crisis intervention as
      well. Even in relatively brief psychotherapeutic encounters, proper methods used
      in a sensitive manner can bring about changes at deeper emotional levels. Women
      need this additional therapy. In the context under study here, psychotherapy
      should not be limited to either behaviour therapy or longer-term procedures.
      Another cooperative model involving both physician and psychotherapist is
      discussed, a model our laws, and society at large, have not yet given due
      support.

PMID- 8991649
TI  - [Personality markers, physical complaints and microsomal thyroid antibody titer
      in postpartum women].
AB  - OBJECTIVE: To define the relation between mood, anxiety, puerperal-depression and
      autoimmune-thyroid-disfunction. PATIENTS AND METHODS: We screened 292 mothers 2
      to 3 days after delivery for anxiety, depression and mood disturbances as well as
      thyroid-function and microsomal antithyroid-antibody status. Ten autoantibody
      positive woman were compared with an equal number of age-matched controls. The
      state-trait-anxiety inventory which consists of 20 questions concerning state
      anxiety (anxiety in a given situation) and 20 questions concerning trait-anxiety
      (anxiety as a quality of personality) was used to describe anxiety. The Beck
      depression-inventory was applied to measure depressive illness. To assess the
      mood we used the "Giessener Beschwerdebogen". RESULTS: We found subclinical
      hypothyroidism in 40% of the antibody positive women and their matched pairs.
      Another 10% of these 20 women showed clinical hypothyroidism. There was no
      significant association of thyroid-function or disfunction with neither anxiety
      nor depressive illness or mood disturbance. The incidence of state-anxiety was
      significantly higher in the antibody positive group than in the antibody negative
      group (Chi2 = 3,3; P < 0.04). Trait-anxiety showed a tendency to be higher in the
      antibody positive group, but the difference was not significant (Chi2 = 2; P <
      0,08). The frequency of depressive illness or mood disturbance at the time of
      assessment was not significantly different in thyroid-antibody positive group
      compared with antibody negative group. CONCLUSION: Autoantibody induced
      thyroiditis may contribute to anxiety in the postpartum period.

PMID- 8991651
TI  - [Pictures by pregnant patients with premature labor. Initial experiences with art
      therapy].
AB  - Patients with preterm labor not only suffer from anxiety and uncertainty
      regarding the healthy development of their child but, especially as inpatients,
      in part severely from loss of autonomy and feelings of insufficiency. By the
      creative therapeutic means of art therapy it is aimed at influencing the
      disturbed emotional state and strengthening self-esteem. During the sessions
      patients experience challenge, success and relaxation with endurance some time
      after the sessions. Paintings produced by hospitalized patients in art
      therapeutic sessions are presented. Further psychophysiological investigations
      are in process for controlling the effects on preterm labor. Paintings of
      inpatients are discussed.

PMID- 8991652
TI  - [How objective is clinical determination of cervix consistency?].
AB  - AIM OF THE STUDY: to establish and classify various degrees of rigidity of portio
      shaped silicone samples tested by obstetricians, midwives and non-medical staff
      by touching. METHODS: to carry out the test, samples with different degrees of
      rigidity, achieved by varying the components mixed together, had to be produced.
      Five samples of different rigidity were touched by 91 testers and were classified
      according to the medical term "soft", "medium", or "rigid". RESULTS: The rigidity
      established could be associated to normal technical dimensions, like Shore
      rigidity for example. The spread of the answers given confirms the need for
      equipment to objectify the determination of cervix consistency. DISCUSSION:
      Possible reasons why the spread was relatively wide, in addition to individual
      subjectivity, may lie in the different nature of the silicone model and a cervix
      in vivo and may also be due to the testing conditions.

PMID- 8991653
TI  - [Combined esophageal atresia and duodenal stenosis in polyhydramnios. Ante-, peri
      and postpartum management].
AB  - Based on a case report of a duodenal atresia, diagnosed by ultrasound in the 30th
      week of gestation, the antenatal investigations and therapeutic proposals are
      demonstrated. Moreover the postapartal development with the extended diagnosis of
      an esophageal atresia as well as the early operative management are discussed.

PMID- 8991654
TI  - [Comment on R. Ratzel: Legal problems in transportation of pregnant patients in
      premature labor with regard to basic and regulated management].

PMID- 8991655
TI  - [Impact of a hepatitis B vaccination program in a population of hospital
      personnel].
AB  - In 1988 a vaccination program against hepatitis B (HBVVP) was initiated in the
      hospital workers of the Consorci Hospitalari del Parc Tauli in Sabadell, Spain.
      The impact of the program and the effectiveness of the vaccine was evaluated. All
      the hospital workers were included in the HBVVP. The proportion of participating
      professionals, the proportion who fulfilled the different stages of the HBVVP and
      the degree of vaccine response were determined. The global coverage of the HBVVP
      was 77%, being higher among the personel with a fixed contracts (90%), the
      morning and afternoon workers (83%), the surgeons (82%), cleaning staff (81%),
      nurses aides (79%) and the workers of acute diseases areas (79%). Eighty-four
      percent of those included fulfilled the complete program with 81% of those who
      underwent the complete scale responding to the vaccine. The coverage and
      fulfillment of the hepatitis B virus vaccination program were high. The results
      of the effectiveness were similar to those of other studies.

PMID- 8991656
TI  - [Hepatic hydatidosis. Review of a series of 677 surgically treated patients].
AB  - A retrospective study of 677 patients who underwent surgery for hepatic
      hidatidosis in the Department of Surgery A and B of the Hospital Miguel Servet in
      Zaragoza, Spain, over the last 21 years is presented. The frequency was analyzed
      in regards to sex, age, symptomatology, cyst data, surgical techniques performed
      and postoperative morbidity. The mean age of the patients was 39 years with the
      incidence being practically equal in both sexes. Dyspeptic symptoms (60%),
      hepatomegaly and/or palpable mass in the right hypochondria (58%) and pain (46%)
      were the most frequent clinical signs and symptoms observed. Radical surgery was
      performed in 21% of all the surgical treatments, while conservative surgery was
      undergone in 79%. Solitary cysts were most frequent (65.7%) with localization in
      the right hepatic lobe (65.4%). The most frequent postoperative complication was
      biliary fistula (72 cases). The rate of reintervention was 18% and operative
      mortality 1.6% with a mean hospitalization period of 25 days.

PMID- 8991657
TI  - [Activity and subcellular distribution of lysosomal enzymes in acute pancreatitis
      induced by CDE diet in mice].
AB  - The aim of the present study was to analyze the activity and subcellular
      distribution of the lisosomal enzymes and the stability of the lisosomes in acute
      pancreatitis induced by CDE diet in mice. The activity and the latency of the
      catepsin-B1 enzymes, acid phosphatase, beta-hexosaminidase and beta-glucuronidase
      in normal pancreas and in pancreatitis induced by CDE diet were determined. The
      distribution of the acid phosphatase lisosomal marker was determined in
      subcellular fractions obtained by differential centrifugation. The activity of
      the catepsin-B1 enzyme increased 47% in the pancreas of mice with pancreatitis
      induced by CDE diet. The acid phosphatase activity was not modified and the beta
      hexosaminidase and beta-glucuronidase was decreased. The specific activity of the
      acid phosphatase lisosomal marker also increased in the subcellular fraction
      containing the zimogene granules and decreased the latency (parameter indicative
      of lisosome stability) of all the lisosomal enzymes analyzed in the pancreatic
      homogenate. These results suggest that the lisosomal enzymes, specially the
      catepsin-B1, and the decrease in the stability of the lisosomes may play a role
      in the pathogenesis of acute pancreatitis.

PMID- 8991658
TI  - [Extrahepatic aneurysm of the portal vein. Apropos of 2 cases].
AB  - Aneurysms of the portal vein are rare and their origin remains under discussion.
      They may be intra or extrahepatic and in some patients previous history of portal
      hypertension may be reported. Nonetheless, numerous cases of congenital origin
      have been observed in which no factors determining their formation have been
      found. Two cases of portal aneurysms of extrahepatic localization who were
      accidentally found in patients with no history of portal hypertension or other
      known etiologic factors are presented.

PMID- 8991659
TI  - [Tuberculous pancreatic abscess: differential diagnosis and favorable response to
      medical treatment].
AB  - Pancreatic tuberculosis is rare and may present differential diagnostic problems,
      specially with cancer of the pancreas. An immunocompetent patient with a
      pancreatic tuberculous abscess whose clinical manifestations were epigastric pain
      and a toxic syndrome of one month of evolution is presented. A cystic mass was
      detected on computerized axial tomography in the tail of the pancreas suggestive
      of irresectable carcinoma because of vascular invasion with negative percutaneous
      cytologic puncture for malignant cells. The patient was surgically treated with
      no histologic confirmation of malignancy. A second laparotomy was performed at 6
      months since spontaneous size reduction, external pancreatic fistula with miliary
      peritoneal dissemination and biopsy compatible with tuberculous granulomas was
      found. Staining for resistant acid-alcohol bacilli were always negative. Medical
      treatment achieved complete disappearance of the pancreatic tumor in one year.

PMID- 8991660
TI  - [HELLP syndrome: case report and review of the literature].
AB  - The case of a 32-years-old primipara in her thirty-second week of pregnancy who
      presented acute epigastric pain, citopenia, elevation in hepatic enzymes and
      analytical signs of hemolysis is presented. Ultrasonography demonstrated multiple
      hyperechogenic nodular images in the liver leading to a wide differential
      diagnosis. Liver biopsy findings, together with the mentioned clinico-biological
      alterations were indicative of the HELLP syndrome. Following caesarean, the
      patient presented rapid and total, symptomatic and analytical, improvement. Based
      on this case, a review of this entity in the literature and its prognostic
      implications and possible therapeutic approaches are reported.

PMID- 8991661
TI  - [Portal thrombosis, common bile duct varices and cholestasis].
AB  - A case of cholestasis in a young patient with portal cavernomatosis is reported.
      This clinical picture is very infrequent and appears as a consequence of
      extrinsic compression on the common bile duct due to which the derivative venous
      collaterals. There does not appear to be any relationship between the intensity
      of the morphologic alteration of the biliary tract and the level of portal
      hypertension and the degree of extrahepatic obstruction. Diagnosis was
      fundamentally achieved by arteriography and retrograde cholangiography with
      differential diagnosis with the previously mentioned diseases being required.
      Chronic cholestasis advises derivative surgery in which difficulties may be found
      due to the presence of thick collaterals in the hepatic pedicle as occurred in
      this patient.

PMID- 8991662
TI  - [Asthma and gastroesophageal reflux. The importance of the anecdote and risks of
      inertia].

PMID- 8991663
TI  - [Organic nephropathies in patients with liver diseases].

PMID- 8991664
TI  - [24-hour pH-metry in the diagnosis of acid-related diseases. Indications and
      usefulness].

PMID- 8991666
TI  - [Cutaneous angiomatous metastasis of hepatocarcinoma].

PMID- 8991665
TI  - [Seroprevalence of hepatitis A antibodies in patients with chronic hepatitis].

PMID- 8991667
TI  - [Reversal of hepatorenal syndrome with oral misoprostol. Is the dose the key to
      the response?].

PMID- 8991668
TI  - [Extreme bradycardia and administration of ranitidine].

PMID- 8991669
TI  - [Endocrine function of the pancreas in patients with organic hyperinsulinism
      syndrome].

PMID- 8991670
TI  - [Results of surgical treatment of nutritional-constitutional obesity by creation
      of "small stomach"].

PMID- 8991671
TI  - [A new method of surgical intervention: endoscopic removal of subdural hematoma
      using microsurgical technique and video system].

PMID- 8991672
TI  - [Endoscopic diagnosis of pyloric stenosis].

PMID- 8991673
TI  - [Effects of enterosorption on manifestations of endogenous intoxication in
      patients with obstructive jaundice of nontumorous etiology].

PMID- 8991674
TI  - [Features of duplex fibula transplantation on a microvascular pedicle].

PMID- 8991675
TI  - [Long-term results of endoprosthesis using hydrophilic polyacrylamide gel
      "Interfall"].

PMID- 8991676
TI  - [Cytological study of wounds using detoxication and nondrug immunomodulation in
      patients with severe burns].

PMID- 8991677
TI  - [Stabilizing effect of enterosorption on the intestinal morphology in burns
      during the toxemia stage].

PMID- 8991678
TI  - [Effects of allogeneic anti-Bacillus pyocyaneus and anti-Proteus plasma humoral
      and cellular immunity in patients with severe burns].

PMID- 8991679
TI  - [Use of a biofragmentable anastomosis ring Valtrac in surgery of the colon].

PMID- 8991680
TI  - [Effects of enterosorption on the morphofunctional state of the hypothalamo
      neurohypophyseal system in severe burns].

PMID- 8991681
TI  - [Cryotherapy using liquid nitrogen in patients with burns during the prehospital
      stage].

PMID- 8991682
TI  - [Effectiveness of enterosorption as a detoxication method in the treatment of
      burns].

PMID- 8991683
TI  - [Advantages of compression biliodigestive anastomoses (an experimental
      morphological study)].

PMID- 8991684
TI  - [Experimental substantiation of the use of ligand-free albumin in burn toxemia].

PMID- 8991685
TI  - [Changes in the pancreatic parenchyma under the effects of different methods of
      cryodestruction].

PMID- 8991686
TI  - [Once again about tactics of the treatment in acute appendicitis].

PMID- 8991687
TI  - [Barrett esophagus: features of structure and diagnostic tactics].

PMID- 8991688
TI  - [Local treatment in anaerobic infections of soft tissues].

PMID- 8991689
TI  - [Concept of producing highly-effective universal cryosurgery equipment].

PMID- 8991691
TI  - [Prevention of burn wound infection in children].

PMID- 8991690
TI  - [Acute profuse gastrointestinal hemorrhage in a patient with extensive thermal
      burns].

PMID- 8991693
TI  - [Plenum of the management of the Scientific Society of Surgeons of Ukraine].

PMID- 8991692
TI  - [Gunshot injury of the aorta].

PMID- 8991694
TI  - [Active surgical treatment of non-Clostridial infection of soft tissues].

PMID- 8991695
TI  - [Fibromyalgia in dentistry]].
AB  - Fibromyalgia represents one of the most frequent musculoskeletal problems. This
      condition, associated with widespread pain, is characterized by a number of
      specific tender points, as well as symptoms such as tiredness, limb stiffness,
      depression and a lack of refreshing sleep. Patients suffering from fibromyalgia
      can also demonstrate the same clinical features as temporomandibular disorders or
      myofascial pain. Dentists should be aware that certain dental treatments will not
      be effective in patients suffering from temporal and masseter pain if
      fibromyalgia has been diagnosed.

PMID- 8991696
TI  - [Primary health care and mental health].

PMID- 8991697
TI  - [The study of cost effectiveness of breast cancer detection in Catalonia].
AB  - BACKGROUND: This study has researched the cost-effectiveness of Early Diagnosis
      of Breast Cancer in Catalonian women in the 50-64 age group. METHODS: The cost
      effectiveness ratio was obtained by comparing the costs of a program for 100,000
      women with results achieved. The program consisted of a twice yearly mammography
      on all of the women over a 10 year period. The study assumed a participation
      level of 70%, detection rate of 0.36%, 92% sensitivity and specificity of 94%.
      RESULTS: A cost-effectiveness ratio of 1,413.648 pesetas was determined per case
      of cancer detected. 705,489 per year of extended life and 783,982 per year of
      extended life adjusted according to quality. Cost-effectiveness of the test in
      the first year was 842,400 per case of cancer detected. 383,183 per year of
      extended life and 425,418 per year of extended life adjusted according to
      quality. CONCLUSION: The results of the study are consistent with those obtained
      by other evaluations and show that early diagnosis of breast cancer is associated
      with a favourable cost-effectiveness ratio.

PMID- 8991698
TI  - [The effect of anti-measles control measures in health care within autonomous
      community of Madrid].
AB  - BACKGROUND: Measles is a disease subject to a child vaceination programme that
      has undergone changes with respect to the epidemiological model employed. The
      purpose of this study is to define the temporal series of measles cases within
      the Autonomous Community of Madrid as of 1971 in each particular Medical Care
      Area, identify the risk of contracting the disease in each such area and to
      evaluate the effect of control measures against outbreaks of the disease. METHOD:
      A descriptive analysis is carried out of the temporal series relating to measles.
      Series components are obtained by means of a multiplication model: seasonal,
      cyclic or irregular trend. The break in transmission of the disease and risk
      attributed to each area is then compared. RESULTS: The number of reported cases
      of the disease decreased by 89% after implementation of the vaccination
      programme: the series has remained stable and it was observed that non-epidemie
      intervals have increased. The risk of contracting measles is greater in four
      Medical Care Areas and the transmission cycle has been broken in 6 Areas.
      CONCLUSIONS: Epidemiological behaviour of measles within the Autonomous Community
      of Madrid does not differ from other countries before and after the
      implementation of vaccination programmes. Evidence of the effects of control
      measures are evidenced by the decrease in the number of reported cases of the
      disease, change in the epidemiological pattern and break in transmission detected
      mainly in the Areas in which such controls have been carried out.

PMID- 8991699
TI  - [The incidence rate of tuberculosis in health care in Alava during 1990-1993].
AB  - BACKGROUND: Study of the incidence and change the number of cases of tuberculosis
      within the Alava Medical Care Area from 1990-1993 and comparison with reported
      cases. METHOD: Active research of tuberculosis cases diagnosed in hospitals
      located in the Area. All cases reported to the Epidemiological Unit of the Alava
      Territorial Health Delegation via the System of Compulsory Declaration of
      Diseases (EDO) were also included. RESULTS: 756 cases of tuberculosis were
      detected, representing an average incidence of 69.4 cases/100,0000 inhabitants.
      There was an increase from 57.3 in 1990 to 86.6 cases/100,000 inhabitants in
      1993, in particular amongst people over the age of 80. People under the age of 20
      not only showed the lowest rate (7.1 cases/100,000 inhabitants) but also remained
      stable over the period analysed. The greatest number of cases were males (71.3%)
      aged from 20-39 (48.9%). 22% of all cases were patients suffering from AIDS. The
      annual increase in the total number of patients was 23.3% as opposed to 12.3% of
      AIDS patients. A deficient level of declaration was observed over the 4 year
      period, gradually decreasing from 28.9% in 1991 to 16.9% in 1993. CONCLUSIONS:
      The incidence of cases of tuberculosis within the Alava Medical Care Area is
      extremely high, showing an increasing trend during the period not covered by
      EDOs, which should be confirmed by a study carried out over a longer period of
      time.

PMID- 8991700
TI  - [Efficiency evaluation of the diabetic education unit at the hospital in
      Algeciras].
AB  - BACKGROUND: Diabetic Education is a basic part of treating Diabetes Mellitus and
      is intended to improve a patient's quality of life. An analysis was made of the
      effectiveness of a diabetic education program at the Algeciras Regional Hospital.
      METHODS: Results achieved by the Diabetic Education Unit were measured according
      to frequency of hospital visits. A parallel study was therefore carried out on
      the Unit's first 86 patients and an analysis made of the percentage of patients
      admitted as well as the period of hospitalization, four years before the Diabetic
      Program was carried out and four years later. RESULTS: The 20.7% rate of patients
      admitted four years before the program was reduced to 6.1% in the four following
      years (IC 95% of the difference between 0.055 and 0.170). A significant decrease
      (p < 0.001) was also observed in the period of hospitalization, before and after
      the program, which was quantified in 3.54 days/patient in four years (IC 95%:
      1.02 to 5.56 days). CONCLUSIONS: The educational program reduced complications of
      the disease and improved quality of life.

PMID- 8991701
TI  - [Diphtheria and poliomyelitis incidence in Europe].
AB  - Vaccinations are considered to be one of the most protitable Public Health
      activities, given that almost three million deaths and four hundred thousand
      cases of polyomyelitis paralysis are avoided throughout the world every year.
      Nevertheless, in under-developed countries, especially Africa, two million
      children die every year from diseases that can be prevented by vaccination. This
      article studies the re-emergence in recent years of diphtheria in Eastern
      European countries (Ukrania, Russia, Belorussia, Poland, ...) and of
      polyomyelitis in countries with no recorded cases of the disease in many years,
      such as the Netherlands, Bulgaria or Transcaucasian Republics and Eastern Asian
      countries formerly of the Soviet Union. An anlaysis is carried out on extent and
      effects, the factors contributing to re-emergence and preventive measures adopted
      to minimise outbreaks and avoid further cases.

PMID- 8991702
TI  - [Characteristics of tobacco use among the primary health care personnel in
      Guadalajara].
AB  - BACKGROUND: Tobaccoism is one of the most important social and health problems
      that exists. Given the role of Health Profesionals as educators and their example
      within the community, this particular group of people are vital in preventing and
      controlling tobaccoism. The purpose of this study was to identify the number and
      type of smokers working as professional health personnel in the Guadalajara
      Primary Medical Care Services, as well as their attitudes and knowledge in
      relation to the problem. METHODS: A descriptive cross-sectional study was carried
      out by means of a survey of all Guadalajara Primary Medical Care Personnel
      (doctors, nurses and other professionals). Data was compiled on social and
      demographic factors as well as the use of tobacco and awareness, attitudes and
      opinions: results were then analysed according to age, sex, occupation, working
      environment and degree of addiction. RESULTS: The rate of response was 86.1%.
      38.2% claimed to be smokers (34.9% men and 41.2% women). Single male doctors
      living in urban areas showed the lowest rate of tobaccism. The majority of
      smokers did so at work, however not in front of patients, 63.2% had tried to give
      up smoking. The main cause of failure was attributed to lack of willpower
      (45.9%). 79.7% of ex-smokers had given up the habit after diagnosis of a health
      problem or illness. With respect to awareness and attitude, it was the medical
      profession and not tobaccoism itself that provided the most effective information
      and created less permissiveness in relation to the habit. Over 90% are in favour
      of initiating anti-smoking programs in Health Departments. CONCLUSIONS: A
      significant number of smokers in the sector was recorded, however attitudes
      towards the problem were positive.

PMID- 8991703
TI  - [Epidemic outbreak of hepatitis B from the tattoo in gypsy families].
AB  - BACKGROUND: To document an outbreak of Hepatitis B in a gypsy community in the
      Upper Aragon region, as well as the control measures adopted. METHODS: Documented
      study of Hepatitis B cases and families, including an epidemiological survey and
      the determining of hepatitis B viral indicators (MVHB) using immunoenzymatic
      methods. RESULTS: 84.8% participation (39/45). During the months of February and
      March 1988, 5 cases of Hepatitis B were detected in a gypsy community in the
      Upper Aragon region (12.8% attack rate, 5/39), with an average age of 13.0 + 7.3,
      (4 women and one man). Four of the cases detected had previously undergone
      tatooing. The fifth case was due to direct transmission from mother to a recently
      born child. The MVHB study of families showed a further two cases. MVHB rate
      being 17.9% (7/39). Vaccinations were given to all persons susceptible to the
      disease. CONCLUSIONS: It is suggested that tatooing could be a significant factor
      to be considered in relation to the transmission of Hepatitis B in gypsy
      communities. Due to the high rate of incidence of the disease in this ethnic
      group, general vaccination is prescribed.

PMID- 8991704
TI  - [Changes in the vascular wall and ischemic damages to the myocardium in
      reversible episodes of heart muscle ischemia].
AB  - When no anaesthetic is used, even 3-5 short-term disturbances of the myocardium
      supply with blood (during a few days) are enough for its initial necrosis and for
      damage of its vascular bed. In acute experiments on rats rutin discovers the
      ability to resist such damages, but on the chronic model of stenocardia in dogs
      its therapeutic effect can be found only under conditions of limitation of the
      ischemic effect by purposefully chosen complex medicinal therapy.

PMID- 8991705
TI  - [The dynamics of 14C-ethanol and 14C-acetaldehyde distribution in rat testes].
AB  - Changes in radioactivity were studied during one day in common proteins,
      karyoplasm and chromatin of testis tissue and in the blood serum of rats after
      administration of (14C)ethanol and (14C)acetaldehyde. In a series of experiments
      the acetaldehyde involvement dynamics was determined on the background of
      disulphiram action. It has been found that the rate of elimination of indicator
      doses of ethanol and acetaldehyde from the blood varies within a day. In the
      interval (2-4 h) the ethanol utilization rate is higher than that of
      acetaldehyde. It is, probably, caused by the activity of ethanol transformation
      enzymes, intensive ethanol oxidation and inflow of the transformation products to
      the tissues. Karyoplasm had the highest level of radioactivity among the
      investigated testis structures. During the day the acetaldehyde accumulation rate
      per a unit of time was several times lower in chromatin, than in karyoplasm.
      These results permit supposing that the testis karyoplasm structures possess the
      mechanisms which inhibit acetaldehyde penetration into chromatin of the male
      generative cells.

PMID- 8991706
TI  - [The activation of proteolytic processes in the periodontal tissues under the
      action of extreme factors].

PMID- 8991707
TI  - [The adaptive characteristics of the small intestine under chronic experimental
      conditions].
AB  - The influence of local substrate loads, both monomeric (glucose) and dimeric
      (saccharose) ones, on the interrelations between the hydrolysis and transport
      processes was studied under conditions of a chronic experiment on rats with
      isolated portions of the small intestine. The use of different substrate loads
      (glucose, saccharose) made it possible to reveal a difference in the response of
      various portions of the small intestine. The distal portions are more sensitive
      to loading than the proximal ones.

PMID- 8991708
TI  - [The functional modulation of neutrophils in mice by humoral factors of the
      nonparenchymatous cells of the intact liver and under an immune influence].
AB  - Cultured nonparenchymatous liver cells of mice produce both thermostable and
      thermolabile factors to influence oxygen-dependent metabolism, degranulation and
      phagocytosis of neutrophils. The liver cells treated with normal xenogeneic
      antibodies (0.5 mg/ml) produce factors to increase neutrophil functional
      activation. Treatment of the liver cells with anti-liver antibodies (0.5 mg/ml)
      results in suppression of neutrophil activation, liver cells produce thermolabile
      factors to suppress neutrophil oxygen-dependent metabolism and phagocytosis.

PMID- 8991709
TI  - [The pathophysiological basis of the destabilization of the clinical course in
      ischemic heart disease].
AB  - The role of the coagulative blood system in initiation of acute coronary events
      was investigated on patients with different clinical forms of ischemic heart
      disease (IHD). The obtained results indicate that unstable angina (UA) and
      myocardial infarction (MI) are two independent forms of the acute IHD with
      distinct qualitative peculiarities. The most common feature of UA was an increase
      in the functional activity of platelets both in cases proceeded in MI and in
      uncomplicated cases. It means that these changes may be treated as the main
      pathogenic factor if UA but not as a mechanism of its transformation to MI. But
      high degree of the risk of MI development appears if these changes are combined
      with preceding significant disturbances in the haemostatic balance as a result of
      inhibition of the activity of anticoagulative and fibrinolytic blood systems.
      These data show that differentiation of the diagnosis between UA and MI in its
      initial stage and the choice of the treatment principles should be based on the
      careful investigation of the coagulative potential of blood and of its most
      important components.

PMID- 8991710
TI  - [The effect of myelopid on the ultrastructural changes in the rat myocardium
      induced by an endotoxin].
AB  - Ultrastructural changes in the myocardial atria and ventricles have been studied
      in experiments on rats in the intermediate period of the endotoxin shock, on the
      stage of late endotoxemia and its correction with myelopid. It was established
      that 5 hours after endotoxin injection contractile disturbances and intracellular
      myocytolysis take place and growth of secretory activity is observed in atrial
      cardiomyocytes. Simultaneously vascular permeability increases. Only the
      endocrine heart function is restored 3 days later, while dystrophic changes and
      glycogen depletion are maintained. The myelopid administration beginning from the
      intermediate period of the endotoxin shock and then once during 3 days, removes
      most of ultrastructural damages or attenuates their expression.

PMID- 8991711
TI  - [The role of the eicosanoids in the development of a postischemic shock
      reaction].
AB  - The role of eicosanoids as one of the main shock mediators was demonstrated in
      experiments anesthetized dogs with modeled postischemic shock using premedication
      with indometacin and/or quercetin. Preliminary administration of the eicosanoid
      biosynthesis inhibitors has prevented reperfusion hemodynamics disturbances
      during 3 hours after the beginning of an extremity reperfusion. The presented
      results confirm vascular endothelium injury in the investigated areas, which
      caused disbalance in the necessity-flow balance in working organs. Therefore, a
      damage in the endotheliocytes function is the first and, probably, a leading
      factor in development of the postischemic disturbances of circulation.

PMID- 8991713
TI  - [The prediction of individual radiosensitivity by the indices of blood
      chemiluminescence in intact animals].
AB  - The possibility of prediction of individual radiosensitivity by the
      chemiluminescence test is considered in this paper. Chemiluminescence is the
      phenomena which reflects a lot of biochemical processes connected indirectly with
      radiosensitivity. It has been established that dependence of the animal mortality
      on the value of the knmax/knmin ratio (kn coefficients of free-radical reaction
      rates) is of the parabolic shape. This agrees with available data that animals
      with extreme deviations of homoeostasis characteristics from average values are
      more susceptible to radiation than animals with characteristics close to average
      ones. Thus, the characteristics k1, k2 and k3 can be recommended as the
      determinants when predicting the radiation injury result.

PMID- 8991712
TI  - [The antioxidative activity of homogenates and lipids obtained from intact and
      ischemic organs in rats].
AB  - The antioxidative activity of homogenates and lipids isolated from the brain,
      heart and liver was studied. The model of thermal autoxidation of linetolum in
      the presence of specimens studied was used. The antioxidative activity of lipids
      from the heart is higher than that of lipids from the brain. Ischemia of the
      organs leads to a practically complete loss of these qualities. The contribution
      of lipids to the general antioxidative activity of the tissue depends on the
      organ peculiarities. The contribution of lipids from the brain to the general
      activity is almost 10 times higher than that of lipids from the liver.

PMID- 8991714
TI  - [Changes in the blood morphofunctional characteristics of cyprinid fishes in
      ammonia poisoning].
AB  - Changes in the carp blood and hemoglobin caused by action of threshold levels
      (0.1 mg/1 litre) of ammonia have been investigated. A decrease in the quantity of
      erythrocytes, increase in the amount of leucocytes and hematocrit are determined.
      Concentration of oxyhemoglobin falls. General hemoglobin, desoxyhemoglobin and,
      particularly, methemoglobin increase. Changes in the curve of dissociation of
      oxyhemoglobin with a shift to the right, which causes an increase in P50 are
      found. Ammonia induces an increase in hemoglobin sensibility to denaturation
      effects of acids and alkalis. Modification of functions and structure of
      hemoglobin is in close connection with such indices of blood and hemoglobin as
      pH, concentration of 2,3-DFG, ammonia, ATP, amid groups of proteins and proteins
      glycation. A conclusion is made that ammonia breaks homeostatic equilibrium of
      blood, its composition and structural functional properties of hemoglobin.

PMID- 8991715
TI  - [The physiological characteristics of the antioxidant properties of Lipin in
      bronchial asthma in children].
AB  - In children of 4-7 years old with bronchial asthma (BA) has been studied the
      values of lipid peroxidation, antioxidant status and some others in blood plasma
      and erythrocytes without and with the use of new drug Lipin. It was shown that in
      children with BA the malondialdehyde concentration increased, the
      superoxydedismutase activity decreased, the NAD concentration increased, and the
      ratio of superoxidedismutase/malondialdehyde greatly decreased in comparison with
      normal children. The use of Lipin led to diminuation of lipid peroxidation, to
      marked increase of superoxidedismutase activity, to decrease of NAD
      concentration, and to significant increase of superoxidedismutase/malondialdehyde
      ratio. These results were indicated on the expressed antioxidant properties of
      Lipin in children's with BA.

PMID- 8991716
TI  - [The effect of ovariectomy and estradiol on DNA, RNA and protein metabolism in
      the adrenal cortex of rats].
AB  - The effects of ovariectomy and oestradiol on incorporation of specific labelled
      precursors into DNA, RNA and protein were studied. Ovariectomy caused a decrease
      in the adrenal weight as well as an increase in the DNA content. That effect has
      been demonstrated most clearly 8 weeks after ovariectomy. Oestradiol treatment of
      ovariectomized rats during 3 days resulted in an increase of incorporation of
      [3H]-thymidine, [3H]-uridine and [3H]-leucine into DNA, RNA and protein,
      respectively. Higher rates of the label incorporation into the tissue from
      animals taken into experiment 8 weeks after ovariectomy were observed.
      Significant changes in incorporation of the specific precursors into DNA, RNA and
      protein were absent in the case of oestradiol treatment of intact rats. These
      data demonstrate that oestradiol have an anabolic effect on metabolism of DNA,
      RNA and protein in the adrenal cortex of ovariectomized rats.

PMID- 8991717
TI  - [A comparative analysis of the level of the main properties of nervous processes
      in youths of different age groups].
AB  - It is found that youths at the ontogenesis stages from 11 to 21 years show a
      gradual increase in the parameters of their neurodynamic functions. The most
      significant increase in the growth rate of the functional mobility and of the
      strength of nervous processes is observed in youths at the initial stages of
      pubescence (14-15 years). At the final stages of their pubescence (16-17 years)
      the neurodynamic of youths is maximally approaching the adults' level.

PMID- 8991718
TI  - [The selenium content of the body in experimental animals and its effect on the
      functional biochemical status of the liver in toxic injury].
AB  - Selenium content in organs and blood as well as the effect of diets with
      different selenium content on the functional and biochemical status of liver in
      toxic damage by tetrachloride carbon and ethyl alcohol was investigated on white
      male rats. Selenium content in the organism of experimental animals has been
      shown to undergo season fluctuations. Both tetrachloride carbon and ethyl alcohol
      have been shown to caise significant disturbances of functional and biochemical
      lever status at the background of selenium-deficient diet whereas selenium
      enriched diet results in much less marked changes in the liver. These
      investigations provide grounds for considering selenium status in the organism
      with respect to preventing possible liver complications due to pathogenic
      factors.

PMID- 8991719
TI  - [The psychophysiological assessment of the functional status of a pilot under
      different conditions of piloting].
AB  - Variations in the cardiac activity and is attention concentration indices of a
      pilot have been investigated during manual flight under various conditions. It is
      shown that the cardiac rhythm rate and variability as well as the level of
      concentration reflect variations in the functional state of a pilot caused by
      varying working conditions and may be used to optimize the flight duty day
      routine, manual flying duration, in-flight work and rest time table as well as to
      assess the flying omission complexity.

PMID- 8991720
TI  - [Serotonin metabolism under the action of a low geomagnetic field].
AB  - We investigated the concentration of the serotonin and monoaminoxydation (MAO)
      activity in the blood and tissues of the internal organs and the content of 5
      oxyindolvinar acid (5-OIVA) in the urine of guinea-pigs at the condition of 10
      days under the influence of the 100-times weakened magnetic field of the earth.
      It was investigated, that the influence of hypogeomagnetic field modulation the
      MAO activity, concentration of the serotonin in the blood and tissues of the
      internal organs, that accompanied by the increase excretion of the 5-OIVA.

PMID- 8991721
TI  - [The effect of adrenoreceptors on the lysosomes of neutrophilic granulocytes
      during the development of the adaptation syndrome].

PMID- 8991722
TI  - [The function of the granulocytic system during immobilization stress with
      immunostimulation].
AB  - The experiments have been carried out on 36 rabbits. The animals of the 1st and
      2nd groups were put to immobilization lying on their backs for 12 hours. The
      rabbits of the 2nd group were injected velozenum into peritoneum for 7 days
      before and after immobilization in order to stimulate immune system. 7-days
      injection of velozenum caused the evolution of neutrophil leucocytosis, raised
      the concentration of circulating immune sets. After immobilization neutrophilesis
      with degradation of neutrophils in both groups of animals that raised activation
      of acid phosphorus. Neutrophilesis and degradation in the 2nd group were less
      marked and protracted. The changes of indices, that characterize the state of
      immune system after immobilization, were purposeful in both 1st and 2nd groups
      identically, but those changes were less marked in the group of animals which
      immune systems had been stimulated. So, the stimulation of immune system reduces
      the activation lysosomal apparatus after immobilization. The regulation of
      homeostasis is possibly implemented in these conditions with the limited
      assistance of lysosomal ferments.

PMID- 8991723
TI  - [The quantitative estimation of the basic parameters of the functional status of
      the human central nervous system].

PMID- 8991724
TI  - [The characteristics of visual information processing in persons of different
      ages].
AB  - Remarked the information of the computer operators (fifty persons aged from 18 to
      67 years) was studied under conditions of the modelled computer operation. The
      results obtained show that the process of remarked the information of operators
      is characterized by a decrease in professional working capacity due to an
      overstrain of physiological reserves of an organism. Dynamics of their ageing
      involution includes four stages: professional training (age 18-21), maximal
      professional working capacity (age 26-28), professional ageing (age 29-40), and
      accelerated professional ageing (age after 40).

PMID- 8991725
TI  - Photodynamic therapy may be alternative to head and neck surgery.
AB  - Photodynamic therapy (PDT) may be used to treat selected cancers of the head and
      neck. Usually done endoscopically, PDT is a minimally invasive alternative or
      adjuvant therapy for cancer treatment. PDT succeeds in destroying malignant cells
      with minimal normal tissue loss.

PMID- 8991727
TI  - Choosing the best protective gloves.
AB  - Gloves should provide two-way protection from the transmission of microorganisms
      between worker and patient. Until recently, glove manufacturers paid little
      attention to barrier properties. Because the operating room is a high-risk area,
      surgical nurses must be especially careful about gloving practices.

PMID- 8991726
TI  - Reprocessing disposables: one strategy to balance cost reduction and quality
      patient care.
AB  - Procedural costs routinely exceed reimbursement. Environmental concerns are
      pressuring hospitals to reduce waste. Standards and protocols have changed,
      removing the barriers to reuse. Reuse of disposables has become a viable option.

PMID- 8991728
TI  - Capture the moment--transferring your surgical skills to the office.

PMID- 8991729
TI  - The operating table: a historical perspective.
AB  - Operating tables evolved rapidly from 1860 through 1920. By 1920, the operating
      tables were well-designed for a wide variety of operations. Today, our operating
      tables resemble those developed in the early 20th century.

PMID- 8991730
TI  - Repairing inguinal hernias laparoscopically.

PMID- 8991731
TI  - Career options--the increasing demand for courtroom nurses.

PMID- 8991732
TI  - Self-determination (Part I).

PMID- 8991733
TI  - Sanese Medical Corporation. Responding to today's needs with tomorrow's design
      and technology.

PMID- 8991734
TI  - The operating room--perceptions of a change in working environment.
AB  - The questionnaire surveyed OR staff on themes such as design, security, and
      workload. Surgical nurses had greater expectations for their roles and functions
      in the new facility. Levels of physical comfort improved; however, mood was not
      affected positively.

PMID- 8991735
TI  - Executive summary.
AB  - The Canadian health system is at a crossroads. Significant health services
      restructuring is occurring across the country. This restructuring process
      provides a unique opportunity for Public Health and others to reorient the system
      away from illness to a focus on health--the health of individuals and
      communities. The purpose of this paper is to motivate and equip Public Health
      workers to take leadership in the restructuring, to outline key responses and
      strategies for Public Health associations, to raise public awareness about
      restructuring, and to challenge decision makers to integrate the Public Health
      perspective into the restructured health system. This Issue Paper describes the
      unique contributions Public Health has to offer health services restructuring,
      outlines the Public Health response to specific restructuring issues, and
      identifies some successful strategies for influencing change. Two key messages
      are explored in the paper: 1. Restructuring will be successful if it is based on
      an investment in health. The health of the public can be maintained and improved
      through changes to the institutional sector and support for health promotion,
      disease prevention and health protection services. 2. Public Health must be a
      full partner in the restructuring of health services. The Public Health
      perspective includes a broad understanding of the issues that are relevant to the
      health of individuals and communities. The skills and knowledge base offered
      through Public Health provide balance and equity in decision making, by ensuring
      full and representative involvement of community workers and the public. The
      uniqueness of Public Health is manifested in three distinct ways: its approach
      within an organized system of practice; its historical contribution; and its
      purposeful combination of perspectives, skills and knowledge. In partnership with
      communities, other health professionals and other health-determining sectors,
      Public Health works to protect, maintain and improve the health of Canadians.
      While other sectors undertake some of the functions outlined below, what makes
      Public Health unique is that these contributions are offered collectively through
      an organized system of practitioners to create a synergistic effect. Eight
      contributions of Public Health are identified in this paper. Specifically Public
      Health: Focuses on individuals and communities in a societal and global context.
      Builds capacity in individuals and communities to improve health. Facilitates
      community mobilization through community participation. Embraces promotion,
      prevention, protection. Influences the orientation of the health system toward
      health outcomes. Provides disease surveillance and control. Builds partnerships
      among sectors at the local level. Advocates for the health of the public. In
      addition to describing these contributions, the Issue Paper addresses the major
      trends in health services restructuring by providing an overview of the issues
      and outlining the Public Health response. While there is no one single model of
      restructuring occurring in the provinces and territories, many common themes
      exist. This paper highlights four categories of restructuring issues: I. Making a
      Difference in Health II. Skills and Knowledge Base III. Allocation of Financial
      Resources IV. Governance and Management.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8991736
TI  - A.E. Grauer: the phantom of public health.

PMID- 8991737
TI  - Cancer incidence and mortality trends in Northeastern Ontario.
AB  - Over 629,000 people reside in the catchment area for the Northeastern Ontario
      Regional Cancer Centre. Historically, the area was renowned for employment in
      mining, forestry and lumbering, agriculture, the railway, and pulp and paper. At
      present, it is known for mining; community, business, and personal services;
      trade; manufacturing; and construction. Comparison of cancer incidence and
      mortality trends for two decades (1971-1980 and 1981-1990) with those of Ontario
      has revealed statistically significant excesses, at the 5% level or better, of
      trachea, bronchus, and lung cancer cases (SIR = 123 for 1971-1980 and 125 for
      1981-1990) and deaths in men (SMR = 116 and 125, respectively); for women,
      excesses were observed for trachea, bronchus and lung cancer case (SIR = 114 and
      118), and cervical cancer cases (SIR = 142 and 115) and deaths (SMR = 133 and
      128). Enhanced recruitment strategies and early educational interventions are
      identified as priorities.

PMID- 8991738
TI  - [Anti-influenza vaccination in a family medicine department].
AB  - This study describes the anti-influenza vaccination coverage of persons aged 65
      or over who presented at the family medicine unit (FMU) of the Saint-Sacrement
      Hospital (Quebec City), between January 1988 and December 1992. All individuals
      were classified according to their anti-influenza vaccination status for each
      vaccination period. In general, the proportion of vaccinated persons increased by
      14.1% during the five-year vaccination period. The mean increase in the
      proportion of vaccinated persons is 22.6% for those seen at least once a year at
      the FMU and 52.6% for those who were vaccinated at the FMU the previous year. The
      study results indicate that regular medical examination and previous vaccination
      increase the likelihood of subsequent vaccination in persons aged 65 or over.

PMID- 8991739
TI  - Correlates of self-rated health in persons aged 85 and over: results from the
      Canadian Study of Health and Aging.
AB  - This report describes self-rated health in 1,239 non-institutionalized Canadians
      aged 85 years and over who participated in the Canadian Study of Health and
      Aging. Most (76.8%) rated their health positively (i.e., very or pretty good).
      Stepwise multiple regression was used to determine the variables that were
      significantly correlated with self-rated health. A modestly successful model for
      predicting self-rated health (R2 = 0.27) was developed. Better understanding of
      the determinants of healthy aging hopefully will lead to effective interventions
      to improve the quality of life of the very old.

PMID- 8991740
TI  - [Delivery of public health services. Proposal for a frame of reference].
AB  - This article proposes a framework for the delivery of public health services by
      the health care system. Considering the many factors associated with a
      population's health status and well-being, health care systems must provide
      public health services in addition to clinical preventive health care services.
      Public health services are distinctive in that they are supplied in response to
      community as opposed to individual needs. The delivery of public health services
      is carried out, in partnership with groups and organizations, through the use of
      strategies that enable, advocate and educate. These strategies, taking place at
      the earliest possible moment in the natural history of problems, act as catalysts
      in the process of change towards health and well-being.

PMID- 8991741
TI  - Survey of Montreal's Aboriginal population's knowledge, attitudes and behaviour
      regarding HIV/AIDS.

PMID- 8991742
TI  - Sexual health: are we targeting the right age groups?

PMID- 8991744
TI  - Income class and pharmaceutical expenditure in Canada: 1964-1990.
AB  - In the 1970s, nearly all Canadian provinces introduced drug programs to subsidize
      purchases by low-income families. This study was undertaken to determine whether
      these programs were successful in reducing out-of-pocket pharmaceutical
      expenditures for low-income families and individuals, and to compare expenditures
      in this group with those of high-income families. Expenditures were calculated
      for a low- and a high-income group from Statistics Canada surveys conducted
      between 1964 and 1990. In the low-income group there was a 40% decline in drug
      expenditure measured as a percentage of total family expenditure and this was
      coincident with the introduction of provincial drug programs. However, the high
      income group had an even larger decrease in drug expenditure. Per capita spending
      as a percentage of total family expenditure in the low-income group, was seven
      times that of the high-income group and there was no change in this ratio after
      the introduction of the drug plans.

PMID- 8991743
TI  - [The "Marrainage" Project: a nonprofessional intervention with families at risk
      for child neglect].
AB  - The "Marrainage" project involves the implementation and evaluation of an
      intervention to prevent negligence in at-risk families with at least one child
      between the age of 0 and 5. The goal of the intervention is to introduce into
      those families, working nonprofessionals who can help them create their own
      natural support network and improve the quality of the family environment. The
      sponsors offer the following support services: emotional support, counselling
      information, physical assistance, social skills development, positive feedback,
      and material needs. The sponsors work most often with the mother. The services
      provided to children consist mainly of outings, games and personal care. Such
      interventions have positive effects on the family environment, particularly on
      the parents' abilities and the psychological well-being of the mother. On the
      other hand, there is no conclusive evidence of a positive impact on the use of
      the families' natural networks.

PMID- 8991745
TI  - Health status of newcomers.
AB  - This article presents and discusses findings on the health status of newcomers
      residing in Windsor, Ontario. The data are part of a larger study, which was
      based on the Ontario Health Survey's questionnaire. Data were collected from 548
      newcomers through home visits, focus groups, mail surveys, and telephone
      interviews. Descriptive multivariate analyses focused on main areas in newcomers'
      physical and mental health status and their access to health services. The
      findings identified that most newcomers do not have acute, life-threatening
      physical problems or chronic illness. They do not experience major problems with
      access to health care or activity limitations. Men are happier, more satisfied
      with their health, and less stressed than women. This study has implications for
      adoption of sensitive transcultural approaches to promote newcomers' health.
      Special challenges lie in women's health and mental health.

PMID- 8991746
TI  - [Health discussions on television: different types of speakers for different
      types of representation].
AB  - The purpose of this paper is to distinguish different types of television
      speakers who, concurrently with the health professionals, talk about eight health
      related behaviours. This analysis covered three weeks of television by two
      broadcasters (756 hours of television). We extracted from the television programs
      the messages and lifestyle images transmitted to the public on the above
      mentioned behaviours. We discovered that the different television speakers
      (health professionals, journalists, show hosts and stars, everyday people,
      fictional characters, advertising and social marketing) are interested at very
      different levels by the studied behaviours, and thus contribute differently to
      the creation of health representation, which is not always in line with health
      promotion measures.

PMID- 8991747
TI  - Focus on health.

PMID- 8991748
TI  - Hospitalization rates of children with gastroenteritis in Ontario.
AB  - PURPOSE: To calculate hospitalization rates of gastroenteritis among children in
      Ontario and to determine the association of hospitalization of gastroenteritis
      with sociodemographic indicators and the availability of hospital beds. METHODS:
      Ontario admission rates were calculated from hospital discharge data for fiscal
      year 1991/92. Small area variations, correlations between sociodemographic
      indicators and admission rates were studied. RESULTS: The age- and sex-adjusted
      admission rate in 1991/92 was 411.1/100,000 with a 14-fold variation in Ontario.
      The availability of paediatric beds was the only significant factor associated
      with high admission rates, with an estimated relative risk of 6.75 (95%
      confidence interval: 1.26, 36.09, p < 0.027). CONCLUSION: Since most children
      with gastroenteritis can be successfully managed as outpatients, high admission
      rates may be an indication of unnecessary hospitalization.

PMID- 8991749
TI  - Changes among retailers selling cigarettes to minors.
AB  - This study analyzes changes over a three-year period among Ontario retailers
      selling cigarettes to minors. Under supervision, 13 and 14-year-old minors were
      sent into stores to attempt to buy cigarettes. These minor-purchase-events (MPEs)
      were carried out in a local health unit that had implemented a community-based
      intervention and in an adjoining comparison health unit. After the local program
      we observed a large reduction (from 46% to 6%) in merchants willing to sell
      tobacco to minors. In the neighbouring health unit, a high rate of selling
      continued until a federal program using a similar intervention was implemented,
      after which a large reduction (from 47% to 2%) was observed. This magnitude of
      change has been unprecedented, except when active enforcement was implemented by
      police officers. Thus, from a public health perspective, it is important to
      understand what is influencing the store operators.

PMID- 8991750
TI  - [Vaccination against influenza in elderly persons: some current presumptions].
AB  - A telephone survey in March 1994 revealed that only 70% of 185 persons surveyed
      aged 65 and over were offered influenza vaccine during the last flu shot
      campaign; the sample was taken among non-institution residents of the Quebec City
      area who were likely to have regular health professional contact. Misinformation
      concerning influenza infection and vaccine remains widespread: 30% of the people
      surveyed still believe that the vaccine can transmit the virus and 21% consider
      the vaccine ineffective. Incorrect beliefs are significantly more prevalent among
      the unvaccinated population: 12% stated that they were allergic to the vaccine;
      in fact, true allergies are rare. Health professionals should recognize that
      elderly people, though in regular contact with the health care system, may not
      have been offered the influenza vaccine and may have inadequate information or
      incorrect beliefs regarding influenza and its preventability.

PMID- 8991752
TI  - [Cigarette taxation: lessons to learn from the 1994 crisis].

PMID- 8991751
TI  - [Study of immunization promotion against influenza in nursing homes and long term
      care facilities in Quebec].
AB  - This study measured the rate of influenza immunization in nursing homes and long
      term care facilities, and evaluated the effectiveness of a promotion program in
      reaching the national objective of 95% coverage. At the end of 1993, data were
      provided by 55 of the 79 nursing homes in the region of Monteregie, Quebec. The
      mean reported immunization rate was 78%, minimum 19% and maximum 100%. In 70% of
      cases, non-vaccination was due to patient refusal. In 1994, an intervention was
      carried out in a random sample of 28 nursing homes. Directors, chiefs of nursing
      and consulting physicians were informed of the coverage achieved in their
      institution in relation to the national objective. In addition, presentations
      were given to the nursing personnel and residents. These presentations were made
      by post-graduate medical students in 22 of the 28 nursing homes in the
      experimental group. No increase in the mean immunization rate was observed,
      indicating that it will be more difficult than expected to reach the desired
      level of coverage.

PMID- 8991753
TI  - [Personal problems related to illicit drug use in dropouts compared to students].
AB  - The consumption of psychoactive drugs and the personal problems related to
      substance use were evaluated among school dropouts and students. Results obtained
      from a self-administered questionnaire among 435 school dropouts were compared
      with those obtained in a previous study among 3,212 students. Drug consumption is
      significantly higher in school dropouts than in students. The proportions of male
      or female youths who report personal problems related to drug use increase
      progressively among the consumers of cannabis, hallucinogens, solvents and
      cocaine for each of the two groups. Moreover, the proportions of school dropouts
      or students who mention difficulties with psychotropic drugs vary inversely with
      the percentages of users for these products. These results suggest that the
      identification of the drug type represents an index for the frequency of personal
      problems related to drug use, and that adolescents at risk form small groups of
      consumers.

PMID- 8991754
TI  - [Results of a deafness screening program for infants: a pilot project].
AB  - This article describes a screening program for hearing loss among infants. The
      program, designed according to ASHA recommendations, was implemented in a public
      health district of the province of Quebec. In the first stage of the program all
      infants born between April 1, 1990 and March 30, 1992 were assessed for risk
      factors for deafness. In the second stage, those infants considered at risk were
      given an audiological examination at six months of age. There were 3,944 births
      during the study period and of these, 8.4% of the infants had at least one risk
      factor for hearing impairment, the most frequent of which was a family history of
      hearing impairment at an early age, followed by: hyperbilirubinemia, admission to
      a high risk neonatal unit, consumption of ototoxic medications, anatomical
      malformations, perinatal infections and insufficient birthweight. Of the infants
      at risk, 54.2% were given the audiological examination at six months and one case
      of deafness was diagnosed.

PMID- 8991755
TI  - [Comprehension of food label claims by university undergraduate students].
AB  - The purpose of this study was to determine whether claims made on food labels are
      well or poorly understood and whether the sex and the experience of consumers in
      buying food products influence their understanding of the various terms used in
      the food industry. A questionnaire was randomly distributed to 285 students
      registered in various undergraduate programs at the University of Ottawa. The
      average grade of all the respondents to the questionnaire was 53.6% which
      indicates a lack of understanding of the meanings of the various terms used in
      the food industry. The results also indicate that more frequent exposure to
      advertising by the food industry is apt to confuse the consumer. Finally, the
      respondents without experience in buying food products answered significantly
      better on three questions; in general, men without experience had significantly
      better results than women on some questions.

PMID- 8991756
TI  - More like war than peace.

PMID- 8991757
TI  - War and peace--part 2.

PMID- 8991759
TI  - International Congress IX on Endovascular Interventions. Scottsdale, Arizona,
      February 11-15, 1996. Abstracts.

PMID- 8991758
TI  - Endoleak--a proposed new terminology to describe incomplete aneurysm exclusion by
      an endoluminal graft.

PMID- 8991760
TI  - Anticoagulation for prosthetic valves during pregnancy.

PMID- 8991761
TI  - 34th Annual American Cytogenetics Conference. Pittsburgh, Pennsylvania, May 4-7,
      1996. Abstracts.

PMID- 8991762
TI  - [100 years after Billroth: "Who has surgical abilities"?].

PMID- 8991763
TI  - [Society of Medical Specialty Professional Organizations].

PMID- 8991764
TI  - [Practice rental contract of the established surgeon].

PMID- 8991765
TI  - [Financial settlement in postoperative hemorrhage--decision of the Federal Social
      Court on 20 December 1995, AZ: 6 Rka 64/94].

PMID- 8991766
TI  - [Concomitant calculation of GOA positions 2006 and 200].

PMID- 8991767
TI  - [Principles and results of systematic lymph node dissection in surgically treated
      bronchial carcinoma].
AB  - Lymphatic spread of bronchial carcinoma can reach any part of the mediastinum,
      irrespective of the localisation of the primary tumor. Metastatic spread may not
      affect all topographical lymph node positions, but this is unpredictable. The
      number of lymph nodes in each position varies. Therefore, systematic mediastinal
      lymph node dissection includes all ipsilateral compartments of the mediastinum.
      It is also possible to reach contralateral sites. In right-sided thoracotomies
      the lymph node dissection is standardized. Mobilizing the aortic arch and the
      large vessels also allows complete mediastinal dissection by a left-sided
      approach. The surgical technique is described. Perioperative morbidity does not
      increase. Systematic mediastinal lymph node dissection is the gold standard for
      evaluation of an exact pN stage. The stage-related survival rate is significantly
      improved. Therefore, it should be required that systematic mediastinal lymph node
      dissection be standard in the surgical treatment of bronchial carcinoma.

PMID- 8991769
TI  - [Principles and value of lymph node excision in colorectal carcinoma].
AB  - Systematic lymphadenectomy for colorectal cancer aims to remove potentially
      metastatic lymph nodes from the tumor's drainage basin. This requires knowledge
      of normal lymphatic anatomy and metastatic routes. Systematic lymphadenectomy
      performed as a standard or as an extended resection is a prerequisite for
      pathologic tumor staging. An intensive search by the pathologist for lymph node
      metastases is critical for precise staging. Recommendations as to the extent of
      lymphadenectomy are derived from potential improvement of prognosis and procedure
      related complications.

PMID- 8991768
TI  - [Lymphadenectomy in tumors of the upper gastrointestinal tract].
AB  - Similar to other tumor entities, complete tumor removal with an adequate safety
      margin in all three dimensions (the oral margin, the aboral margins and the tumor
      bed) must be the primary aim of any surgical approach to carcinoma of the upper
      gastrointestinal tract. The same goal has to be achieved in the area of the
      lymphatic drainage. All positive nodes and nodes with a so-called
      'microinvolvement' have to be removed together with the primary tumor. The safety
      margin of lymphadenectomy can be estimated by the lymph node ratio, i.e., the
      ratio between the number of removed and positive nodes. Several studies have
      shown that for carcinoma of the upper gastrointestinal tract the prognosis can be
      improved markedly if the lymph node ratio is below 0.2. For tumors in the early
      phase of lymphatic metastasis this can be achieved by extensive lymph node
      dissection. In practice, this requires as a minimum a lymphadenectomy of
      compartments I and II of the tumor's lymphatic drainage (D2 lymphadenectomy). The
      individual compartments are determined by the embryogenesis of the affected organ
      and defined by the tumor location. In patients with advanced lymphatic
      metastases, lymphadenectomy does not improve the prognosis and can only result in
      a reduction of local recurrences. Lymphadenectomy does not increase the risk and
      morbidity of the surgical procedure, provided it is restricted to the removal of
      nodes. These basic principles of lymphadenectomy are valid for carcinomas of the
      esophagus, cardia and stomach.

PMID- 8991770
TI  - [Principles and value of lymph node excision in tumors of the pancreatobiliary
      system].
AB  - Malignancies of the gallbladder, bile ducts and pancreas have a very bad
      prognosis compared with other gastrointestinal malignomas. Lymph node metastasis
      has frequently been identified as an important prognostic factor. This leads to
      some surgeons to embark on an extremely aggressive resectional strategy,
      including wide lymphadenectomy. So far, reported results of these procedures have
      varied considerably and concomitant morbidity has often exceeded that of standard
      resections. Until there is unequivocal proof of the benefit of an extended
      lymphadenectomy in controlled studies this strategy cannot be recommended
      generally.

PMID- 8991771
TI  - [Kidney donation by the elderly--an emergency solution?].
AB  - In 1994 the number of kidney donors once again decreased in Germany. On the other
      hand, more and more old people are being considered for renal transplantation;
      thus the shortage of transplants is becoming more severe. The kidneys of elderly
      donors might improve this situation. The results available are inconsistent.
      There is no doubt that kidney function declines with age, but the individual
      aging process depends mainly on concomitant disease, especially arterial
      hypertension. Transplantation of kidney from an elderly person requires
      appropriate selection of donors as well as good perioperative management. Doctors
      in medical intensive care units should contact transplant centres more often to
      evaluate potential elderly kidney donors. More open-minded assessment of certain
      situations is necessary in conservative medical disciplines.

PMID- 8991772
TI  - [Lymph node dissection, stage migration and perioperative risk in rectal
      carcinoma].
AB  - In 348 patients with an initial diagnosis of rectal carcinoma operated on between
      1985 and 1994 we investigated the quality of lymph node dissection, its influence
      on the perioperative risk and tumor staging. The same histopathological work-up
      was carried out in all cases. Whether resections or extirpations were performed,
      the number of dissected lymph nodes increased from 5.3 and (1985/1986) to 16.7
      and 17.3 (1991/1992) and to 15.8 and 17.3 (1993/1994) respectively. Neither the
      type of operation nor the surgeon's experience had a significant influence on the
      number of lymph nodes dissected. The increase in the number of lymph nodes
      dissected had no negative effect on the length of the operation, the amount of
      blood infused during the operation or the perioperative risk. We found a
      significant correlation between the number of lymph nodes dissected and the
      number of lymph node metastases (P = 0.02) and between an increase in UICC stage
      III (P = 0.005) and pN2 tumors (P = 0.000) and an increase in the number of lymph
      nodes dissected. Central lymph node dissection by high ligation of the inferior
      mesenteric artery did not increase the perioperative risk in spite of the fact
      that in recent years we have observed more patients with multiple diseases.

PMID- 8991773
TI  - [Surgery of inguinal hernia in Switzerland in 1994. A survey of 142 teaching
      clinics in Switzerland].
AB  - With a response rate of 60.6% to a questionnaire sent out in 1994 it is possible
      to give an overview of the situation in hernia surgery at the 142 surgical
      clinics of Switzerland. In general, regional anesthesia is the preferred method
      (67.4%). Together, Shouldice repair and fascia transversalis repair cover over
      90% of the repair techniques in primary hernias. In recurrent hernias the same
      techniques dominate (70.2%) a large spectrum of different operation methods;
      implantation of foreign materials is rare (5.9%). Only 4.5% of all Swiss surgical
      clinics have some experience with endoscopic hernia surgery.

PMID- 8991774
TI  - [Must the recurrent nerve in thyroid gland resection always be exposed? A
      prospective randomized study].
AB  - It was the purpose of this study to establish whether it is necessary to identify
      the recurrent laryngeal nerve intraoperatively when resecting the endemic nodular
      goiter. We prospectively formed two groups from 800 subtotal unilateral
      resections ("nerves at risk"). In group I (382 subtotal resections, 48.4%) the
      nerve was not identified intraoperatively. In group II (413 subtotal resections,
      51.6%) the recurrent laryngeal nerve was routinely identified in all cases. The
      operative technique was standardized, giving special attention to the "anterior
      lamella". For all patients, preoperative and postoperative evaluation of the
      vocal cords was performed routinely. Altogether we saw 4 (0.5%) transient vocal
      cord palsies: 2 in group I and 2 in group II. All 4 laryngeal nerve palsies
      recovered within 4 months. These data demonstrated that no benefit is gained from
      routine dissection of the laryngeal nerve during resection of endemic nodular
      goiter. Therefore the demand for obligatory intraoperative identification of the
      recurrent nerve is not tenable.

PMID- 8991775
TI  - [Morbidity in concomitant interventions in neck exploration for primary
      hyperparathyroidism. Results of a prospective study].
AB  - A prospective follow-up study was undertaken in patients undergoing surgical
      therapy for primary hyperparathyroidism to establish the frequency of concomitant
      surgical procedures and their influence on the morbidity of cervical exploration.
      From 1 August 1987 to October 1995, 231 patients underwent cervical exploration
      for primary hyperparathyroidism. In 16 patients 18 (7.8%) concomitant abdominal
      and thoracic surgical procedures as well as surgical interventions for soft
      tissue tumors were performed. A total of 133 patients (57.6%) underwent thyroid
      resections of varying extent; 4.8% had carcinoma of the thyroid. Catamnestic data
      were obtained on the basis of a standardized follow-up in 94.4% of all patients
      (1-9 follow-up examinations in 216 patients). Hematoma occurred after
      adrenalectomy in a patient undergoing a concomitant extracervical procedure. In
      patients with a first manifestation of primary hyperparathyroidism due to a
      solitary parathyroid adenoma (n = 189), an increase in the morbidity of
      parathyroid surgery performed in combination with a thyroid resection was
      observed. Furthermore, a relationship was established between the number of
      intraoperatively identified parathyroid glands and the incidence of permanent
      hypoparathyroidism (permanent hypoparathyroidism: initial cervical intervention
      with parathyroid exploration alone, 2.2%; with concomitant thyroid resection,
      6.5%; after secondary thyroid resection and parathyroid exploration alone, 0%;
      after concomitant thyroid resection, 28.6%; four parathyroid glands identified
      intraoperatively, 3.1%; fewer than four parathyroid glands identified, 8.2%). The
      increase in the morbidity of parathyroid surgery in combination with thyroid
      resection is justifiable, because unsuspected thyroid carcinomas can potentially
      be treated curatively.

PMID- 8991776
TI  - [Surgical therapy of advanced hemorrhoidal disease--is an ambulatory surgery
      intervention possible?].
AB  - Hemorrhoidal disease is the most common pathophysiologic abnormality in the anus
      in the western civilized world. Sixty years after publication of the method in
      The Lancet, hemorrhoidectomy according to Milligan and Morgan and modifications
      of their methods are still considered the standard procedure in cases of advanced
      hemorrhoidal disease. During the last 5 years, 107 patients underwent
      hemorrhoidectomy in the Department of Surgery at the University of Cologne. In
      most of these patients, the operation followed Milligan and Morgan's method.
      There were 69 males and 38 females with a mean age of 47.9 years. Mean length of
      hospital stay was 4.5 days. We saw one case of postoperative bleeding that
      required operative review. The patients' risk profile (age, concomitant diseases,
      ASA classification) did not influence the length of the hospital stay. Operative
      hemorrhoidectomy according to Milligan and Morgan allows a short stay in hospital
      according to the individual needs of the patient, with a high degree of safety
      concerning possible postoperative complications.

PMID- 8991777
TI  - [Right hemihepatectomy using a frontal approach--alternative to the conventional
      procedure].
AB  - Right hemihepatectomy is an anatomically based major resection technique for
      primary and metastatic liver cancer. The most dangerous step in the procedure is
      to mobilize the right liver lobe from the retroperitoneum and the inferior vena
      cava. Large tumors or those with extension to the diaphragm, adrenal gland, or
      kidney may be more easily resected if a frontal approach to dividing the liver is
      followed. After dissection of the hilus, the liver is divided and during this
      step all vessels draining to the vena cava are separated. Then the right liver
      lobe is mobilized together with surrounding structures if necessary, but with no
      significant risk of bleeding. Our experience in four patients operated on for
      metastases or different primary tumors demonstrated that this frontal approach
      may be safely used and allows minimal manipulation of the tumor. Intraoperative
      ultrasound may be helpful in the detection of the middle and right hepatic vein.

PMID- 8991778
TI  - [Open laparoscopic approach--an alterative to the Veress needle. Experiences
      after 1,000 laparoscopies].
AB  - A mini-laparotomy as described by Hasson was used in a modified way in 1000
      laparoscopic procedures. In comparison with the insertion of a Veress needle we
      find the open approach to be a safer and quicker way of obtaining
      pneumoperitoneum.

PMID- 8991779
TI  - [Manually assisted laparoscopic surgery--realistic evolution of the minimally
      invasive therapy concept? Initial experiences with the "Endohand"].
AB  - The essential limitations of laparoscopic procedures--lack of palpation,
      problematic retrieval of specimen and anastomosis, etc.--are abolished by the
      hand of the surgeon, which is inserted into the peritoneal cavity through a mini
      laparotomy. While holding the pneumoperitoneum, the hand acts as an intelligent
      instrument performing surgical exploration, exposition of the field of operation,
      blunt dissection or intracorporal knot-tying. The mini-laparotomy is used to
      insert conventional instruments and suture material, as well as for specimen
      retrieval and anastomosis. Our preliminary experience (3x splenectomy, 2x sigmoid
      colectomy, 1x anterior resection of rectum, 1x proctocolectomy with J-pouch)
      shows that even extensive laparoscopic operations are accomplished much more
      simply. The time spent for such procedures is markedly reduced.

PMID- 8991780
TI  - [Tumor embolism with fatal cerebral infarct in pneumonectomy. Case report and
      review of the literature].
AB  - Carcinomas of the bronchi often infiltrate veins, particularly in advanced
      stages. Tumor propagation in pulmonary veins with intra-atrial extension has been
      reported. Systemic arterial tumor embolism is a potentially fatal hazard that is
      caused by surgery or it can be the initial manifestation of a bronchogenic
      carcinoma. The importance of early pulmonary venous ligation in lung cancer
      surgery, first stressed by Aylwin in 1951, is evident, particularly when
      intravenous tumor progression has been diagnosed preoperatively by
      echocardiography or CT scan. We report a case of lethal hemispheric brain
      infarction following tumor embolism during lobectomy for bronchus carcinoma. A
      review of the literature on this subject is presented; there were 38 cases of
      arterial tumor embolism because of primary lung neoplasms.

PMID- 8991781
TI  - [Laparoscopic resection in Crohn disease. Comment on the contribution by U.
      Hildebrandt et al].

PMID- 8991782
TI  - Development of neurotrophic factor therapy for Alzheimer's disease.

PMID- 8991783
TI  - The effects of D-23129, a new experimental anticonvulsant drug, on
      neurotransmitter amino acids in the rat hippocampus in vitro.
AB  - D-23129 [N-(2-amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester] and
      D-20443 (dihydrochloride of D-23129) are promising anticonvulsant compounds with
      a broad spectrum activity in animal models of epilepsy. Their effects on de novo
      synthesis of excitatory (glutamate and aspartate) and inhibitory (GABA) amino
      acids were studied in rat hippocampal slices. Like phenytoin, carbamazepine,
      lamotrigine, losigamone, U54494A, and flupirtine, D-23129 and D-20443 were
      effective in preventing the effects of a chemoconvulsant, 4-aminopyridine, on de
      novo synthesis of the three amino acids. However, unlike the other compounds, D
      23129 and D-20443 also preferentially increased the concentrations of newly
      synthesized GABA. Their effect on the neosynthesis of GABA was unique, dose
      dependent, and not tetrodotoxin sensitive. A total of 15 compounds (including
      standard, new and candidate anticonvulsants) either had no effect on new GABA or
      decreased it. Therefore, D-23129 and D-20443 exhibited two different effects on
      de novo synthesis of neurotransmitter amino acids, both of which could
      potentially be anticonvulsant in nature.

PMID- 8991784
TI  - Changes in transport of [14C] alpha-aminoisobutyric acid across the blood-brain
      barrier during pentylenetetrazol-induced status epilepticus in the immature rat.
AB  - In the present study, we measured the effects of pentylenetetrazol (PTZ)-induced
      status epilepticus on the blood-brain barrier (BBB) permeability in rats at
      postnatal age 10 (P10) or 21 days (P21). Seizures were induced by the repetitive
      injection of subconvulsive doses of PTZ until the onset of status epilepticus
      characterized as the loss of quadruped posture. The BBB permeability changes to
      the poorly diffusible amino acid [14C] alpha-aminoisobutyric acid (AIB) were
      measured by autoradiography at 10 min after the onset of status epilepticus.
      Seizures induced a generalized increase in BBB permeability to AIB that was
      significant in 22 and 26 regions out of the 34 studied at P10 and P21,
      respectively. Highest increases over control levels (> 250%) were recorded at
      both ages in interpeduncular nucleus, raphe nuclei and trigeminal nerve tractus.
      Quite high increases (> 150%) were recorded in cortical, inferior collicular and
      thalamic areas at P10 and in inferior colliculus, cerebellar cortex, hypothalamic
      and thalamic regions at P21. Cerebral blood volume measured with [14C]sucrose
      over a 2-min period was significantly increased over control levels in
      hypothalamus and cerebellum at P10 and in all brain regions, except hippocampus
      and brainstem, at P21. The widespread increase in BBB permeability is at least
      partly related to the blood pressure increase, 55 and 22% over control values at
      P10 and P21, respectively. In the P10 rat, generalized BBB leakage appears to be
      correlated to the widespread increase in cerebral metabolic and blood flow rates
      that we recorded previously in the same experimental conditions. Conversely, at
      P21, as previously shown in adults, there is a mismatch between the nature of the
      structures with increased BBB permeability and the regional distribution of
      cerebral blood flow and metabolism changes induced by PTZ seizures.

PMID- 8991785
TI  - Effects of various valproic acid derivatives on low-calcium spontaneous
      epileptiform activity in hippocampal slices.
AB  - Lowering of extracellular calcium induces the development of spontaneous
      epileptiform activities in rat hippocampal slices. The antiepileptogenic effect
      of four new sugar-ester derivatives of valproic acid--dimethylenexylitol
      valproate, monoacetoneglucose valproate, diacetoneglucose valproate and glucose
      valproate--were investigated on such activity through 20-min bath applications
      and their effect compared to that of valproate, valpromide and phenytoin. Sodium
      valproate, 5 mM, did not completely suppress the spontaneous epileptiform
      activity. Valpromide, 2.5 mM, and phenytoin, 0.25 mM, produced complete cessation
      of seizure activity. Dimethylenexylitol valproate, 0.1 mM, completely suppressed
      spontaneous epileptiform activities. The other derivatives were less potent:
      concentrations of 0.25 mM of monoacetoneglucose valproate and 1 mM of
      diacetoneglucose valproate and glucose valproate were required for complete
      cessation of activity. The sugar carriers alone were devoid of effect. The data
      show that these molecules have a direct action on the nervous tissue and their
      antiepileptogenic efficacy in the low-calcium model is far larger than that of
      valproic acid itself. Such derivatives, especially dimethylenexylitol valproate,
      appear to be promising for development of new antiepileptic molecules.

PMID- 8991786
TI  - Effects of zonisamide on dopaminergic system.
AB  - Effects of zonisamide (ZNS) on extracellular dopamine (DA), its precursor 3,4
      dihydroxyphenylalanine (DOPA), its metabolites 3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA) levels in the striatum as well as hippocampus
      of freely moving rats were studied. Intracellular DA, DOPA, DOPAC and HVA levels,
      as well as DOPA accumulation as an index of tyrosine hydroxylase activity in the
      rat brain in vivo, DA re-uptake in the striatum and hippocampus, and monoamine
      oxidase (MAO) activities were also determined. Acute administrations of
      therapeutic ZNS doses (20 and 50 mg/kg) increased striatal extracellular DOPA
      levels, intracellular striatal and hippocampal DOPA levels, and stimulated DOPA
      accumulation in both brain regions. ZNS also increased striatal and hippocampal
      intracellular as well as extracellular DA and HVA levels, but decreased those of
      DOPAC levels. Chronic (3 weeks) administrations of therapeutic ZNS doses (20 and
      50 mg/kg/day) increased intracellular DA, DOPA, DOPAC and HVA levels in striatum
      and hippocampus. ZNS-induced changes were greater in intracellular levels than in
      extracellular levels. Acute and chronic supratherapeutic ZNS dose (100 mg/kg)
      administration decreased intracellular levels of all substances detectable in
      both brain regions, and inhibited DOPA accumulation. Both subtypes of MAO (type A
      and type B) activities were weakly inhibited by ZNS. ZNS showed no effect on DA
      re-uptake in striatum nor in hippocampus. These results suggest that therapeutic
      ZNS doses increase DOPA accumulation as well as both intracellular and
      extracellular DA, DOPA and HVA levels. However, such doses also decrease
      extracellular and intracellular DOPAC levels by enhancing DA synthesis and/or by
      selectively inhibiting MAO-B activities. In addition, chronic therapeutic ZNS
      dose administration enhances DA synthesis, which results in increased
      intracellular DA, its precursor and its metabolites levels. On the other hand,
      both acute and chronic supratherapeutic ZNS dose administrations inhibit DA
      turnover. These ZNS effects on DA metabolism are at least partly involved in the
      mechanisms of action of ZNS.

PMID- 8991787
TI  - Effects of levetiracetam, a novel antiepileptic drug, on convulsant activity in
      two genetic rat models of epilepsy.
AB  - The anticonvulsant effects of levetiracetam were assessed in two genetic rat
      models. In the audiogenic-seizure prone rat, levetiracetam, 5.4 to 96 mg/kg i.p.
      dose-dependently inhibited both wild running and tonic-clonic convulsions. In the
      GAERS model of petit mal epilepsy, levetiracetam markedly suppressed spontaneous
      spike-and-wave discharge (SWD) but left the underlying EEG trace normal. The
      effects were already marked at 5.4 mg/kg and did not increase significantly up to
      170 mg/kg although more animals were completely protected. Levetiracetam produced
      no observable effects on behaviour apart from slight reversible sedation at 170
      mg/kg. In contrast, piracetam, a structural analogue of levetiracetam,
      significantly and consistently suppressed SWD in GAERS rats only at the high dose
      of 1000 mg/kg with some slight effects at lower doses. The effect of piracetam
      appeared to be due to increased sleeping rather than to a direct antiepileptic
      effect. The results with levetiracetam argue for a clinical application in both
      petit mal, absence epilepsy and in treating generalised tonic-clonic and partial
      seizures.

PMID- 8991788
TI  - Carbamazepine and PIP-syndrome in temporal lobe epilepsy.
AB  - We describe four patients with left temporal lobe epilepsy who developed
      psychosis, intermittent polydipsia and hyponatremia (PIP-syndrome) while being
      treated with carbamazepine. These cases illustrate the close links between
      dysfunction of the limbic system causing epileptic seizures and psychosis on the
      one hand and dysregulation in hypothalamic centers manifestating in polydipsia
      and osmodysregulation on the other.

PMID- 8991789
TI  - Pharmacokinetics of tiagabine as add-on therapy in patients taking enzyme
      inducing antiepilepsy drugs.
AB  - The effect of hepatic enzyme-inducing antiepilepsy drugs (AEDs) on the clinical
      pharmacokinetics of tiagabine, a new AED, was studied in the steady-state
      condition. Patients with epilepsy entered this two-day study on a previously
      stable regimen of one to three enzyme-inducing drugs (phenytoin, phenobarbital,
      carbamazepine, and/or primidone) and tiagabine.HCl (24, 40, 56, or 80 mg daily).
      Patients were confined on both days, and serial blood samples were collected.
      Plasma tiagabine concentrations were determined by high-performance liquid
      chromatography; pharmacokinetic parameters were calculated using noncompartmental
      methods. Tiagabine pharmacokinetics were linear at all doses, as substantiated by
      the lack of significant differences among groups for dose-adjusted Cmax, Cmin,
      and AUC0-6. Some diurnal variation occurred, as evidenced by a statistically
      significant time effect for dose-adjusted AUC0-6. The effect was small, however,
      and possibly not clinically relevant. The harmonic mean half-lives of 3.8 to 4.9
      h were remarkably constant across dosages and shorter than those of historical
      control subjects not taking enzyme-inducing AEDs suggesting that epilepsy
      patients not taking enzyme-inducing AEDs may require lower tiagabine.HCl doses to
      achieve the plasma levels observed in patients taking these drugs.

PMID- 8991790
TI  - Genetic linkage studies in familial frontal epilepsy: exclusion of the human
      chromosome regions homologous to the El-1 mouse locus.
AB  - Familial frontal epilepsy has been recently described in six pedigrees. All
      families reported show autosomal dominant inheritance with incomplete penetrance.
      Affected individuals develop predominantly nocturnal seizures with frontal lobe
      semiology. In 1959, a genetic mouse model for partial epilepsy, the El mouse, was
      reported. In the El mouse, a major seizure susceptibility gene, El-1, segregates
      in an autosomal dominant fashion and has been localized to a region distal to the
      centromere of mouse ch 9. Comparative genetic maps between man and mouse have
      been used to predict the location of several human disease genes. The El-1 locus
      in the mouse is homologous to human chromosomes 3p23-p21.2, 3p11.2-q11.2, 3q21
      q25.3, 6p12-q12 and 15q24. Polymorphic microsatellite markers covering these
      candidate regions were used for genotyping individuals in the three larger
      families ascertained, one of which is French-Canadian and two are Australian.
      Significant negative two-point and multipoint lod scores were obtained separately
      for each family, thus excluding linkage with the candidate regions on chromosomes
      3, 6 and 15.

PMID- 8991791
TI  - Progress report on new antiepileptic drugs. A summary of the Second Eilat
      Conference.
AB  - The Second Eilat Conference on New Antiepileptic Drugs was held at the King
      Solomon's Palace Hotel from October 31 to November 3, 1994. Epileptologists and
      scientists from 20 countries attended the conference, which was held to discuss
      new trial designs, drug approval, early use of new antiepileptic drugs, and new
      drugs in development. Over the last six years, several novel antiepileptic drugs
      have been introduced worldwide, and new information on their safety and efficacy
      has become available. These include felbamate, gabapentin, lamotrigine,
      oxcarbazepine, and vigabatrin. Drugs in development include those at an advanced
      stage, such as topiramate and tiagabine, as well as those just entering clinical
      trials, such as remacemide and levetiracetam. The following is a summary of the
      presentations for drugs in development and newly marketed drugs. The meeting
      concluded with a presentation, 'Still Searching for the Magic Bullet'.

PMID- 8991792
TI  - Phenylketonuria, an international survey of management over 40 years. Proceedings
      of a workshop. Fulda, November 16-19, 1994.

PMID- 8991793
TI  - Precursors of prostatic adenocarcinoma: recent findings and new concepts.

PMID- 8991794
TI  - Behavioural analysis of changes in nociceptive thresholds produced by remoxipride
      in sheep and rats.
AB  - The antinociceptive potential of remoxipride was investigated in sheep and rats
      with concurrent motor function assessments. Previous studies of sheep given
      intravenous remoxipride have revealed increases in mechanical nociceptive
      thresholds. Here, further investigation in sheep demonstrated elevated thermal
      nociceptive thresholds with no effect on subjectively assessed sedation or motor
      impairment scores. However, in rats, the dose of remoxipride (100 mg/kg i.p.)
      required to produce nociceptive thresholds similar to those elicited by morphine
      (30 mg/kg i.p.), itself reduced rotarod performance. Medetomidine (200
      micrograms/kg i.p.) evoked sedation without influencing rotarod performance or
      antinociception. The antinociceptive, motor deficit and cataleptogenic actions of
      remoxipride were similar to those induced by two other dopamine antagonists,
      haloperidol (5 mg/kg) and raclopride (16 mg/kg i.p). Tocainide (100 mg/kg i.p.)
      induced thermal antinociception with normal rotarod performance and no catalepsy
      suggesting that Na+ channel blockade by remoxipride is not responsible for the
      changes in nociceptive thresholds. This study emphasizes the importance of motor
      function assessment during acute antinociceptive testing.

PMID- 8991795
TI  - Lipoxin A4 inhibits cholinergic neurotransmission through nitric oxide generation
      in the rabbit trachea.
AB  - The effect of lipoxin A4 and lipoxin B4 on cholinergic neurotransmission in
      rabbit tracheal segments was studied under isometric conditions in vitro. Lipoxin
      A4 attenuated the contractile responses to electrical field stimulation and
      caused a rightward shift of the frequency-response curves, so that the stimulus
      frequency required to produce a half-maximal effect (ES50) increased from 8.1 +/-
      0.8 to 25.7 +/- 1.9 Hz (P < 0.001), whereas lipoxin B4 had no effect. In
      contrast, lipoxin A4 did not alter the contractile responses to acetylcholine.
      Pretreatment of tissues with NG-nitro-L-arginine methylester inhibited the effect
      of lipoxin A4 on electrical field stimulation, but NG-nitro-D-arginine
      methylester did not. This inhibition by NG-nitro-L-arginine methylester was
      reversed by L-arginine but not by D-arginine. These results suggest that lipoxin
      A4 prejunctionally reduces the vagal nerve-mediated contraction of airway smooth
      muscle, probably by inhibiting the release of acetylcholine, and that this effect
      may be exerted through stimulation of nitric oxide generation.

PMID- 8991796
TI  - Radioligand binding affinity and biological activity of the enantiomers of a
      chiral melatonin analogue.
AB  - Melatonin, a hormone secreted by the pineal gland, can act on the central
      circadian oscillator in the suprachiasmatic nucleus of the hypothalamus. It has
      been proposed that melatonin or its analogues may be useful in restoring
      disturbed circadian rhythms in jet-lag, shift-work and some blind subjects, and
      as sleep-promoting agents. In the present study, the (-)- and (+)-enantiomers of
      N-acetyl-4-aminomethyl-6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole (AMMTC)
      were separated and tested. The affinity of the enantiomers at the specific 2
      [125I]iodomelatonin binding site in chick brain membranes was compared in
      competition assays, and their biological activity in a specific melatonin
      receptor bioassay, aggregation of pigment granules in Xenopus laevis
      melanophores. The (-)-enantiomer of AMMTC was 130-fold and 230-fold more potent
      than the (+)-enantiomer in competition radioligand binding assays and
      melanophores, respectively. Both enantiomers are melatonin receptor agonists; (-)
      AMMTC is slightly more potent than melatonin itself. As the tetrahydrocarbazole
      nucleus holds the C-3 amido side-chain of AMMTC in a restricted conformation, the
      analogues will be useful in modelling the melatonin receptor binding site.

PMID- 8991797
TI  - Attenuation of memory with Tyr-D-Arg-Phe-beta-Ala-NH2, a novel dermorphin analog
      with high affinity for mu-opioid receptors.
AB  - The involvement of mu-opioid receptors in memory retrieval was examined in mice
      by using Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA), a novel dermorphin analog with high
      affinity for mu-opioid receptors, and passive avoidance learning. TAPA was
      intracerebroventricularly administered to mice before retention tests of passive
      avoidance learning. A 0.3-ng dose of TAPA markedly shortened step-down latency of
      passive avoidance learning, and the shortening of step-down latency was reversed
      by treatment with beta-funaltrexamine (5 micrograms), a mu-opioid receptor
      antagonist, indicating that TAPA (0.3 ng) attenuates memory retrieval. Although
      the attenuating dose (0.3 ng) of TAPA failed to affect horizontal or vertical
      locomotor activity, a 3-ng dose of TAPA showed a tendency to decrease vertical
      locomotor activity. A 30-ng dose of TAPA produced a significant increase in
      horizontal locomotor activity accompanied by a marked reduction of vertical
      locomotor activity. TAPA (3 ng) produced a significant increase in step-down
      latency of passive avoidance learning with lower intensity of electroshock or
      without electroshock during training. These results suggest that the activation
      of mu-opioid receptors impairs memory retrieval.

PMID- 8991798
TI  - The effect of the desglycinyl metabolite of remacemide on cortical wedges
      prepared from DBA/2 mice.
AB  - Remacemide hydrochloride is currently undergoing clinical trials for use as an
      anticonvulsant agent in the treatment of epilepsy. It is considered that the
      desglycinyl metabolite (FPL 12495AA) of the parent compound accounts for the
      majority of the anticonvulsant activity. In this study we have investigated the
      effects of FPL 12495AA on electrical activity in the cortical wedges prepared
      from audiogenic seizure-prone DBA/2 mice. FPL 12495AA at varying concentrations
      (50-200 microM) significantly reduced both the spontaneous depolarizations (IC50
      102 microM) and the associated afterpotentials (IC50 50 microM) which are
      characteristic in this preparation under magnesium-free conditions. The compound
      also concentration-dependently reduced N-methyl-D-aspartate (NMDA)-induced
      depolarizations of the tissue (IC50 43 microM) and the antagonism by FPL 12494AA
      was not overcome by increasing NMDA concentrations. FPL 12495AA had no effect on
      (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-induced
      depolarizations. The results suggest that FPL 12495AA has a specific antagonistic
      effect on the NMDA receptor complex possibly through non-competitive inhibition
      at the phenycyclidine site in the ion channel. Such an action could contribute to
      its anticonvulsant properties.

PMID- 8991800
TI  - Effects of granisetron, a 5-HT3 receptor antagonist, on morphine-induced
      potentiation of brain stimulation reward.
AB  - Using the curve-shift method, we studied the effects of four doses (0.003, 0.03,
      0.3 and 3 mg/kg, s.c.) of granisetron (endo-N-(9-methyl-9-azabicyclo[3.3.1]non-3
      yl)-1-methyl-1H-indazole-3- carboxamide hydrochloride), a selective 5
      hydroxytryptamine3 (5-HT3) receptor antagonist, on the potentiation of brain
      stimulation reward by microinjection of 2.5 micrograms/0.25 microliters of
      morphine sulphate (7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol sulphate)
      into the ventral tegmental area. As previously reported, morphine produced a
      significant reduction in reward threshold without altering maximal rates of
      responding. Granisetron attenuated the potentiating effect of morphine at the
      highest dose and failed to alter reward threshold or maximal rates of responding
      when given alone, except at the lowest dose where a small and statistically
      significant increase in threshold was found. These results provide additional
      evidence that 5-HT3 receptor antagonists may reduce the rewarding effect of
      opiates and do not impair the ability to produce operant responses. The weak
      attenuation observed with granisetron alone suggests that 5-HT3 receptors are
      unlikely to constitute an important influence on the directly stimulated reward
      relevant pathway(s).

PMID- 8991799
TI  - Endotoxin-induced changes of endothelial cell viability and permeability:
      protective effect of a 21-aminosteroid.
AB  - Endotoxic shock results in endothelial cell dysfunction and oedema formation.
      Endotoxin decreased in a concentration-dependent fashion endothelial cell
      viability with maximum effects by adding 10 micrograms/ml lipopolysaccharide for
      48 h (47 +/- 15% and 22 +/- 2.6% of control cells in the presence or absence of
      foetal calf serum, respectively). Furthermore, incubation (10 h) with lower
      concentrations of lipopolysaccharide (1 microgram/ml) significantly increased
      endothelial cell permeability to 250% compared to control values. The 21
      aminosteroid U-74389G (10 microM) prevented the cytotoxic effect of
      lipopolysaccharide as well as the lipopolysaccharide-induced increase in
      endothelial cell permeability. By contrast, the glucocorticoid methylprednisolone
      was less effective even at higher concentrations (100 microM). The effect of
      lipopolysaccharide is possibly due to oxidative stress and/or membrane
      destabilization rather than to the induction of inflammatory mediators, because
      of the reduced efficacy of the glucocorticoid.

PMID- 8991802
TI  - Functional role of endothelin ETA and ETB receptors in venous and arterial smooth
      muscle.
AB  - The functional importance of endothelin ETA and ETB receptors in selected
      arterial and venous smooth muscle preparations was characterized. Endothelin-1
      induced force in the saphenous and jugular veins is normally mediated by
      endothelin ETB-like receptors. However, desensitization or pharmacological block
      of these receptors reveals an endothelin ETA receptor population that is of
      sufficient size to mediate full endothelin-1-evoked force. Block of either
      endothelin ETA or endothelin ETB receptors alone is insufficient to antagonize
      endothelin-1-evoked force in saphenous vein. Endothelin-1-induced force in
      hamster aorta may also be mediated by activation of both endothelin ETA and ETB
      receptors. However, activation of endothelin ETB-like receptors alone is
      insufficient to generate a full endothelin-1 response. Sarafotoxin S6c treatment,
      to desensitize endothelin ETB receptors, failed to affect the responses of rat
      aorta and rabbit carotid artery to endothelin-1 or endothelin ETA receptor
      antagonists. These findings indicate that selective endothelin receptor
      antagonists will vary enormously in their efficacy against endothelin-induced
      force in different vascular beds.

PMID- 8991801
TI  - Neuropeptide Y inhibits depolarization-stimulated catecholamine synthesis in rat
      pheochromocytoma cells.
AB  - In PC12 rat pheochromocytoma cells differentiated with nerve growth factor (NGF),
      neuropeptide Y inhibited depolarization-stimulated catecholamine synthesis as
      determined by in situ measurement of 3,4-dihydroxyphenylalanine (DOPA) production
      in the presence of the decarboxylase inhibitor m-hydroxybenzylhydrazine (NSD
      1015). The inhibition by neuropeptide Y was concentration-dependent and was
      prevented by pretreatment with pertussis toxin, suggesting the involvement of a
      GTP-binding protein of the Gi or Go subtype. The neuropeptide Y analog
      [Leu31,Pro34]neuropeptide Y also caused inhibition of DOPA production, but was
      less potent than neuropeptide Y itself, while peptide YY and neuropeptide Y-(13
      36) had no significant effect. This pattern is most consistent with the
      involvement of the neuropeptide Y Y3 receptor subtype. In PC12 cells
      differentiated with dexamethasone, neuropeptide Y also caused a concentration
      dependent inhibition of DOPA production, while peptide YY was again without
      effect. Neuropeptide Y had no effect on DOPA production in undifferentiated PC12
      cells. These results indicate that neuropeptide Y can modulate catecholamine
      synthesis in addition to its modulatory effects on catecholamine release.

PMID- 8991803
TI  - Prejunctional actions of K+ channel blockers in rat vas deferens.
AB  - In studies of isometric contractions in prostatic portions of rat vas deferens
      evoked by single pulse electrical stimulation, the K+ channel blockers 4
      aminopyridine, tetraethylammonium and charybdotoxin, but not apamin,
      significantly reduced the prejunctional inhibitory potency and the maximum
      inhibitory effect of the alpha 2-adrenoceptor agonist xylazine. The protein
      kinase C activator phorbol dibutyrate had similar effects to 4-aminopyridine
      against xylazine. However, 4-aminopyridine, tetraethylammonium, charybdotoxin and
      phorbol dibutyrate, but not apamin, significantly increased the magnitude of the
      isometric contraction to a single stimulus. 4-Aminopyridine and phorbol
      dibutyrate significantly reduced, while tetraethylammonium did not affect,
      isometric contractions to noradrenaline, and 4-aminopyridine failed to affect
      contractions to alpha,beta-methylene-ATP, so that the effects of these agents on
      the isometric contraction to a single stimulus were presumably by a prejunctional
      action. The Ca2+ entry facilitator Bay K 8644 (1,4-dihydro-2,6-dimethyl-5-nitro-4
      [2-(trifluoromethyl)-phenyl]-3-pyrid ine carboxylic acid methylester) increased
      stimulation-evoked contractions by a postjunctional action and reduced the
      inhibitory effects of xylazine. When the isometric contraction following 4
      aminopyridine was reduced by decreasing the stimulation voltage or by reducing
      the Ca2+ concentration from 2.5 to 0.9 mM, 4-aminopyridine significantly reduced
      the potency of xylazine. However, tetraethylammonium and Bay K 8644 failed to
      affect the inhibitory potency of xylazine in low Ca2+. It is concluded that the
      K+ channel blocker 4-aminopyridine reduces the prejunctional inhibitory potency
      of xylazine, and this action is independent of increased neurotransmitter
      release. These results suggest that prejunctional alpha 2-adrenoceptor-mediated
      inhibition in rat vas deferens involves K+ channels sensitive to block by 4
      aminopyridine.

PMID- 8991805
TI  - Positive action of propionyl-L-carnitine on mechanical performance of papillary
      muscle from Syrian hamsters with hereditary dilated cardiomyopathy.
AB  - Propionyl-L-carnitine has been shown to exert a beneficial effect on cardiac
      function in different experimental models of cardiomyopathy in the rat, most
      likely by improving cardiac metabolism and energy production. We have previously
      shown that, in a strain of hamsters with hereditary dilated cardiomyopathy (BIO
      TO.2), the mechanical activity of papillary muscle (length-tension, velocity of
      shortening, shortening, work and power relationship) is significantly depressed
      when compared to the same parameter in normal hamsters (BIO F1.B). The repeated
      oral treatment with propionyl-L-carnitine (60 mg/kg per os for 7 weeks) to BIO
      TO.2 hamsters had a significant positive inotropic effect, as indicated by an
      increase in developed tension up to the levels observed in papillary muscles from
      normal hamsters. This action is most likely associated with metabolic effects
      similar to those observed in rats.

PMID- 8991806
TI  - The alpha 1-adrenoceptor agonist, SDZ NVI-085, behaves as a potent, competitive
      antagonist of 5-hydroxytryptamine-induced contraction of rat aorta.
AB  - In this study we investigated the actions of SDZ NVI-085 ((-)-(4aR,10aR)
      3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl -9-(methylthio)-2H- naphth[2,3-b)
      1,4-oxazine hydrogen malonate), previously classified and employed as a selective
      alpha 1-adrenoceptor agonist, in the rat isolated aorta assay. It was shown that,
      in addition to its alpha 1-adrenoceptor agonistic action, SDZ NVI-085 behaves as
      a competitive antagonist of 5-hydroxytryptamine (5-HT)-induced contraction of rat
      aorta (pKB = 8.13 +/- 0.08). The structurally related alpha 1-adrenoceptor
      agonist, SK & F 89748-A (l-1,2,3,4-tetrahydro-8-methoxy-5-(methylthio)-2
      naphthalenamine hydrochloride), produced inhibition of the 5-HT response only at
      the highest concentration tested (1 microM) with an associated pA2 value of 6.0
      +/- 0.1. These findings suggest that the affinity of SDZ NVI-085 for 5-HT2
      receptors is considerably higher than for alpha 1-adrenoceptors, which may have
      implications for its use as a pharmacological tool.

PMID- 8991804
TI  - Cerebral ischemia in gerbils: effects of acute and chronic treatment with
      adenosine A2A receptor agonist and antagonist.
AB  - Despite significant progress in understanding of the potential of adenosine A1
      receptor-based therapies in treatment of cerebral ischemia and stroke, very
      little is known about the effect of selective stimulation of adenosine A2A
      receptors on the outcome of a cerebrovascular arrest. In view of a major role
      played by adenosine A2 receptors in the regulation of cerebral blood flow, we
      have investigated the effect of both acute and chronic administration of the
      selective adenosine receptor agonist 2-[(2-aminoethylamino)
      carbonylethylphenylethylamino]-5'-N- ethylcarboxoamidoadenosine (APEC) and
      antagonist 8-(3-chlorostyryl)caffeine (CSC) on the outcome of 10 min ischemia in
      gerbils. Acute treatment with APEC improved recovery of postischemic blood flow
      and survival without affecting neuronal preservation in the hippocampus. Acute
      treatment with CSC had no effect on the cerebral blood flow but resulted in a
      very significant protection of hippocampal neurons. Significant improvement of
      survival was present during the initial 10 days postischemia. Due to subsequent
      deaths of animals treated acutely with CSC, the end-point mortality (14 days
      postischemia) in this group did not differ statistically from that seen in the
      controls. It is, however, possible that the late mortality in the acute CSC group
      was caused by the systemic effects of brain ischemia that are not subject to the
      treatment with this drug. Chronic treatment with APEC resulted in a statistically
      significant improvement in all studied measures. Although chronic treatment with
      CSC improved postischemic blood flow, its effect on neuronal preservation was
      minimal and statistically insignificant. Mortality remained unaffected. The
      results indicate that the acute treatment with adenosine A2A receptor antagonists
      may have a limited value in treatment of global ischemia. However, since
      administered CSC has no effect on the reestablishment of postischemic blood flow,
      treatment of stroke with adenosine A2A receptor antagonists may not be advisable.
      Additional studies are necessary to elucidate whether chronically administered
      drugs acting at adenosine A2 receptors may be useful in treatment of stroke and
      other neurodegenerative disorders.

PMID- 8991808
TI  - [The law 626/94 and epidemiology].

PMID- 8991807
TI  - Relaxant effect of levcromakalim in isolated human small subcutaneous arteries.
AB  - The effect of levcromakalim, an ATP-sensitive K+ channel opener, on isolated
      subcutaneous arteries from mammary tissues obtained from female patients
      undergoing reconstructive breast surgery was investigated. The small arteries
      were preserved in the University of Wisconsin (UW) solution. The contractile
      responses to K+ and 9,11-dideoxy-11a,9a-epoxy-methano-prostaglandin F2 alpha
      (U46619) and the relexant responses to levcromakalim and to the endothelium
      dependent vasodilator, methacholine, in these arteries remained fully intact
      after preservation in UW solution for at least 5 days. The pD2 value and maximal
      relaxation obtained from the concentration-response curve of levcromakalim (n =
      7) were 5.78 +/- 0.23 and 81 +/- 6%, respectively. The vasodilator effect of
      levcromakalim was significantly antagonised by the ATP-sensitive K+ channel
      blocker, glibenclamide (1 and 3 microM). In conclusion, isolated human arteries
      contain ATP-sensitive K+ channels, which can be modulated by K+ channel openers
      and blockers. Subcutaneous small arteries, as used in our experiments, appear to
      be very suitable for pharmacological experiments.

PMID- 8991809
TI  - [Application of clinical audit to the evaluation of prescription of interferon
      alpha in a teaching hospital].
AB  - Aim of this study was to evaluate through an audit tool the appropriateness of
      interferon-alpha (IFN-alpha) prescribing in a teaching hospital. The records of
      all patients (n.665) treated with IFN-alpha since 1991 were reviewed and the data
      concerning diagnosis and treatment collected using a standardized from. The data
      were submitted for peer review to a panel which included the representatives of
      the different medical specialties which actually prescribed the drug, external
      experts and members of the health management board of the hospital. The following
      points were discussed:-adherence to accepted therapeutic indications:-accuracy of
      the diagnosis prior to treatment:-scheduled doses:-criteria defining non
      responders;-length of treatment and criteria for discontinuation. At the end of
      the study a questionnaire for evaluation of the audit was submitted to all
      participants. Most patients were treated according to a diagnosis of chronic
      hepatitis (HCV, n.448; HBV, n.54; HDV, n.22); other indications were chronic
      myeloid leukemia, thrombocythemia, polycythemia vera, Kaposi's sarcoma,
      condylomata, melanoma and mycosis fungoides. All indications were approved by the
      panel: no patient was treated outside established indications (85.6%) or a
      clinical trial protocol (14.4%). Standard schedules were initially applied to
      each indication, and were adjusted if needed according to the clinical response.
      In conclusion, the audit showed that IFN-alpha was correctly prescribed in our
      teaching hospital; the procedure was well accepted and its application may be
      useful in modifying prescribing attitudes.

PMID- 8991810
TI  - [Influence of the environment on perineal tears in physiological delivery].
AB  - INTRODUCTION: In the last decades there was a growing interest in new methods of
      delivery-assistance and in the literature appeared many new studies. This study
      shows an analysis of all physiological deliveries (581 women) at the Burresi
      Hospital of Poggibonsi (SI), Italy, in 1993. From 1984, in this hospital an
      experimental delivery-room (SPN), where new methods of delivery-assistance are
      tested (151 women in the period of study), has been used in parallel with a
      conventional delivery-room (SP)(430 women). RESULTS: The most important
      difference between the two environments is that in SPN the woman is free to
      choose her positions during all the phases of delivery. We have evaluated the
      effect of the different environments on the perineal outcome-intact perineum (41%
      SPN vs 32% SP), first-degree tears (32% SPN vs 21% SP), second-degree tears (23%
      SPN vs 21% SP) and mediolateral episiotomy (3% SPN vs 26% SP). Age of the woman,
      weight of the infant and parity appeared to be most important factors for
      perineal tears. The SPN reduces significantly the number of perineal tears, when
      allowing for the other factors. CONCLUSION: It was commonly felt that a reduction
      in the episiotomy-rate increases the number of perineal tears. Our study shows a
      protective effect for all levels of perineal outcomes associated with the natural
      delivery-room. However, for primiparous women a higher risk for first-degree
      tears is documented in the SPN and should be further evaluated. A selection bias
      cannot be excluded, due to the observational nature of the present investigation.

PMID- 8991811
TI  - [Evaluation of a health education program for preventing alcohol and tobacco
      abuse in a health unit in Lombardi, Italy].
AB  - The effectiveness of a health education programme for prevention of alcohol abuse
      and tobacco smoking among adolescents was assessed by an intervention study with
      a non-randomized control group. The study was carried out among 7th-9th grade
      school students in a Local Health Unit of the Brescia province, North Italy.
      Students were enrolled in either the intervention or the control group, based on
      the participation of their teachers to the educational programme. A total of 428
      students were involved in the programme representing the intervention group, and
      658 students not involved in the programme formed the control group. The health
      education programme included the prevention of alcohol abuse in the first school
      year (1989-90) and the prevention of tobacco smoking in the second year (1990
      91). Each part of the programme included a series of lessons taken by the
      teachers for about 20 hours. Alcohol use and smoking habits, knowledge about, and
      attitudes toward alcohol and tobacco use of the students have been assessed by
      anonymous questionnaires. The questionnaires have been administered during school
      time at the beginning and the end of each school year, giving a total of 6
      questionnaires, from Q1 to Q6. All the questionnaires included the same questions
      on alcohol and tobacco use, knowledge and attitudes. Of the 1086 students who
      attended the 7th grade in the year 1989-90, 428 were enrolled as intervention
      group and 658 as control group. As regards alcohol, the following findings were
      observed: 1. no difference was found in the percentages of students drinking at
      least one glass of wine or beer daily between the 2 groups at Q6; 2. no
      substantial change in the percentage of students aware of the health risks of
      alcohol abuse from Q1 to Q6 was observed. As regards tobacco smoking, the results
      of the study showed: 1. no difference between the 2 groups was found at Q6 as
      regards the proportion of students who smoked one or more cigarettes a month; 2.
      the percentages of students planning to smoke in the future were similar in the 2
      groups in Q6; 3.the percentage of students with a high score on the health
      consequences of smoking was higher in the intervention than the control group at
      Q4, but again no difference between the groups was evident at Q6. In conclusion,
      the health education programme seemed to be unsuccessful in modifying behaviors
      and attitudes regarding alcohol and tobacco use during the 3-year follow-up.

PMID- 8991812
TI  - [The role of public health professionals in the face of health problems].

PMID- 8991813
TI  - [A case-control study for lung cancer in two municipalities of the province of
      Modena, Italy, which has been generated by local current mortality studies].

PMID- 8991814
TI  - [Characteristics and outcome of interventions offered to drug users attending
      public treatment centers in Lazio, Italy].
AB  - In 1991 the Lazio Region set up a surveillance system which collects individual
      data on each drug user attending Public Treatment Centres (PTCs). The analysis of
      surveillance system data allows not only to describe the characteristics of
      treatments but also to analyse determinants of treatment outcomes. In this study
      the outcome of treatment was evaluated in 5.646 drug users who attended public
      centres in 1992. The outcome was defined in two categories: positive (subjects
      who completed the therapeutic program, were referred to different service or were
      still in treatment) negative (subjects who refused or dropped out treatment,
      arrested or dead). Drug users usually receive more than one treatment in one
      year, 60% of them successfully completed. Methadone treatment shows the highest
      level of compliance while naltrexone the lowest. The negative outcome is highly
      associated with sex, type of treatment, length of treatment and outcome of
      previous treatment. Males are more likely to experience a negative outcome than
      females. Those offered naltrexone are more likely to refuse and drop out than
      those offered psychosocial treatment. Long term treatments are more successful
      than shorter ones. Furthermore, drop out is higher among those who have dropped
      out in the past. Although this observational study might not permit conclusions
      on the efficacy of each type of treatment, it allows an evaluation of the
      selection procedures at the treatment centres. Treatment centres for drug users
      in Lazio tend to select clients according to standard therapeutic treatment
      protocols instead of making treatments more accessible to drug users.

PMID- 8991816
TI  - [Proceedings of conference on the pathology of environmental and occupational
      pollutants. Modena, Italy, 12 September 1994].

PMID- 8991815
TI  - Somatostatin Analogues: Basic and Clinical Perspectives. Proceedings of a
      meeting. Sorrento, Italy, 16-19 November 1995.

PMID- 8991817
TI  - [Importance of the specific surface area in the study of the biological effects
      of dusts of industrial use].
AB  - We have studied a sample of commercial sepiolite and two samples of commercial
      vermiculite which are advised to replace asbestos, and we have in vitro tested
      their abilities to activate the complement and to lyse erythrocytes. Their
      behaviours has been compared with those of asbestos fibres given by Union
      Internationale Contre le Cancer (UICC) as reference standards. We have first
      measured the specific surface area and the weight of each mineral. Sepiolite has
      been inactive in complement activation and little able to lysis red blood cells
      on the base of surface area; on the base of the weight it has been unreactive in
      complement activations but very reactive in red blood cells lysis. We believe
      that in the in vitro assays to evaluate the biological effects of the substitutes
      of asbestos it is very important to considerate as the weight and as the specific
      surface are of each clay mineral.

PMID- 8991818
TI  - [Concentration of asbestos fibers in urothelial tumors and in the neoplasm-free
      bladder wall].
AB  - The aim of our study was to search the eventual presence of asbestos fibers in
      the neoplastic tissue of 13 cases of bladder carcinoma and in the normal vesical
      tissue of 12 control cases without neoplasia and operated upon for other urologic
      pathologies. To all patients a standardised questionnaire has been administered
      in order to ascertain the entity of the eventual exposition to asbestos. The
      organic component of the tissues has been oxidated at low temperature in atomic
      oxygen plasma and the residual inorganic component has been analysed by
      transmission electronic microscopy and energy dispersion spectrometry. We have
      found asbestos fibers only in two over the 25 examined samples; in both cases
      they belonged to patients affected by the neoplasia and in one of them also by
      pulmonary asbestos. The procedures that we used in this study, in respect to our
      other experiences, allowed us to reduce the risk of contamination of the tissues
      by asbestos, as it is shown by the lower number of cases with positive finding of
      fibers and by lower concentration of fibers in the positive cases.

PMID- 8991819
TI  - [Goal-oriented projects of the Emilia Romagna region].
AB  - The Region of Emilia Romagna, on the basis of a 1983 specific regional law,
      funded two triennal plans of applied health researches. The fundamental criteria
      and the characteristics of these two plans are described. A particular attention
      is devoted to the projects concerning environmental and occupational health. The
      role of the local occupational health services in performing research activities
      and in using the results of the research projects are also described.

PMID- 8991820
TI  - [Herbicides and neoplasms of the hemolymphopoietic system].
AB  - The study is a population-based case-control study on hematolymphopoietic tumors,
      conducted in west Liguria with high prevalence of exposure to chemicals suspected
      (about 10%) of increasing the risk of leukaemias or lymphomas and multiple
      myeloma (pesticides). Cases and control were identified and confirmed during the
      period 1/1/1990 through 31/12/1993. Cases are identified through periodic
      contacts with the Pathology, or Hematology or other relevant Department of the
      Hospitals of west Liguria and Genoa town or University of Genoa where patients
      living in these area are referred for hematolymphopoietic malignancies. Controls
      are a random sample of the general population living in each area (using the
      demographic health archives). The range of the age is 20-74. After identification
      each case or control is contacted to have his consent to the interview near the
      home. Informations collected using a most completed questionnaire regard drinking
      and smoking habit, the addresses and the conditions of the homes where spending
      the life, particularly hobbies about exposure of pesticides and/or solvents, more
      important pathological events on the life and the occupational exposure. Actually
      we are in the phase of identification of cases and controls.

PMID- 8991821
TI  - [Mortality by tumors and other causes in dairy cattle and other agricultural
      workers in Veneto].
AB  - The study was conducted to verify a reduction in mortality from tumors in dairy
      farm workers, exposed to endotoxins, which increase in the host a cytotoxic
      antitumoral. From the SCAU files of the Province of Padova, we selected 2.415
      subjects with informations on: date of hire, date of work termination, number of
      dairy cattle, area of the farm. The vital status was ascertained through the
      Communes of residence, and for the 541 decedents the cause of death was
      established. The standardized mortality ratio (SMR) was calculated on the basis
      of age-sex-cause-calendar period specific mortality rates in the Veneto. In the
      1.641 dairy farm workers, SMRs were significantly low for total tumors (= 81) and
      lung tumors (= 66), and significantly high for brain tumors (= 283). In other 774
      farmers, no significant SMRs were observed. The data will be further processed to
      verify a dose-response relationship with the occupational risk indicators.
      Smoking habits will be collected.

PMID- 8991822
TI  - [Retrospective study of the morbidity in a group occupationally exposed to
      chlorotriazine herbicides: preliminary results].
AB  - Two different groups of workers, involved in production or formulation of
      chlorotriazine herbicides during the last 10 years, have been retrospectively
      studied for occurrence of diseases related to the exposure to Atrazine, Simazine,
      Propazine, and Terbuthylazine. A control group has been selected between clerical
      workers of the same plants. Subjects exposed to the different compounds have been
      studied for inhalator and dermal exposure by active sampling, skin pads, and hand
      washings; samples have been further processed and specifically analysed. Urines
      have been studied for the presence and concentrations of mono and bidealkylated
      triazine metabolites. Exposure data have been collected during the last five
      years and extrapolations have performed for exposures in the preceding years.
      Clinical finding and laboratory data for all workers have been obtained from
      medical surveillance records. Data available for the last 10 years have been
      evaluated to highlight possible differences between the investigated groups.

PMID- 8991823
TI  - [Immuno-histopathologic changes in the gastrointestinal mucosa in patients with
      nickel contact allergy].
AB  - The study concerns the histological and immunohistochemical findings of the
      gastrointestinal mucosa of 20 patients (group A) suffering from contact allergic
      dermatitis (CAD) to Ni, with symptom recrudescence due to food ingested Ni.
      Results were compared with those observed in 20 patients suffering from CAD to Ni
      (group B), without sensitivity to food ingested Ni, and in 20 normal subjects
      (controls). The sensitivity to food ingested Ni, as suggested by history, was
      demonstrated by placebo-controlled oral-Ni challenge. The biopsies for
      histological and immunohistochemical study were performed during endoscopy and
      obtained from the antrum and from the duodenal mucosa. In the biopsies obtained
      from 16 of group A patients there was evidence of inflammatory infiltrate of
      lymphocytes and plasma cells with oedema and vasodilation in the lamina propria.
      Slight flattening of the villi and enlongation of the crypts were concomitant.
      These findings were light in the 4 patients of group A and in 11 of group B and
      instead were absent in the remaining group B patients and in the controls.
      Immunohistochemically, lymphocytes in the lamina propria were prevalently CD20 +
      (B cells) and CD4 + (Th cells), some were CD45RO + (memory) and finally few CD8 +
      (Tc/s cells). CD45RO + cells was found in cluster in patients of group A and in 4
      of group B, whereas in the others were isolated. Since some studies have shown
      that immunological pattern of skin reaction to Ni is characterized by increased
      CD45RO + cells, it may be hypothesized that in patients suffering from CAD to Ni,
      the sensitivity to food-ingested Ni may be induced by a type IV immunological
      reaction in the gut.

PMID- 8991824
TI  - [Health risks from infrared emissions from radiant tube heaters in the
      workplace].
AB  - With the exception of domestic rooms, Overhead Radiant Tube Heaters (ORTH) are an
      effective system for indoor heating (e.g. warehouses, factories, garage
      workshops, shipyards, greenhouses, schools hall etc.). The growing number of
      units installed is due to several advantages, such as uniform heating, absence of
      air movements, energy saving, versatility and safety. Indoor heating is obtained
      by an infrared emission, which is produced by the circulation of combustion
      exhaust gases within tubes and is collected by a set of reflecting surfaces
      located around the tubes. In the present communication, the attention is driven
      on the characteristics of ORTH infrared emissions, with reference to potential
      health risks for the exposed people (especially people working within areas
      heated by this system). A reason for this is represented by the existence of a
      specific italian regulation (Circolare N. 1322/4134-28.01.1992, Direzione
      Generale della Protezione Civile-Ministero dell'Interno). Following the last one,
      ORTH surface temperatures resulting in a spectral emission which includes
      wavelengths less than 3 microns have to be considered, in the case of ORTHs with
      thermal power greater than 34.89 kW, as hazardous for exposed people. Although
      the ORTHs emission spectrum partially covers the near infrared region (0.8-1.4
      microns) at 400 degrees Celsius and may adversely affect the retained tissue a
      gross evaluation of the near infrared energetic flux, weightened on the surface
      unit, allows to exclude this risk. On the opposite, the results of the same
      evaluation carried out in the medium and far infrared spectral region at 200
      degrees-400 degrees Celsius (the normal temperature range for ORTHs) do not allow
      to preliminary exclude a thermal risk for eye structures such as lens, near the
      tube surface at least. In every case, a burn hazard for both corneal tissue and
      skin is excluded. With the aim to carry out a detailed set of radiometric
      estimates, some preliminary considerations are furnished concerning the risk
      assessment for the eye, with reference to the following parameters: emission
      spectrum, energetic flux, workstation, presence of reflecting surfaces, potential
      interferences, exposure duration, angle between the incident radiation on eye
      surface and the optic axis. ACGIH 1992/93 for infrared radiation TLVs are
      followed as reference standard.

PMID- 8991825
TI  - [The goal-oriented project "pathology of environmental pollutants" (M.U.R.S.T.
      40%)].
AB  - The purpose of this study was to estimate to toxicity bound to effluent water,
      pore water and bed sediment sampled twice during 1994 (spring and autumn) from 16
      tributaries of Po river. Toxicity was determined by using a battery of bioassays
      (Artemia salina, Dugesiagonocephala and Thamnocephalus platyurus) and a battery
      of phytoassays, including Oryza sativa and Triticum sativum. Results show that
      practically no toxicity is found in effluent water, mild adverse effects are
      obtained with sediment pore water, while the most harmful compounds are those
      bound to sediment particles. These data strengthen the hypothesis that sediment
      is the true historical memory of the ecotoxicological conditions of a water body.
      Finally, the map of our results illustrates that pollution severity is
      progressively increasing from western to eastern tributaries in Po river valley.

PMID- 8991826
TI  - [Toxicologic effects of cadmium on gametes and embryonal kinetics of
      paracentrotus lividus].
AB  - The adverse effects of cadmium chloride or cadmium sulphate on both fertilization
      of sea urchin eggs by spermatozoa and cadmium treated embryos have been studied.
      Cd treated ova can be fertilized by control spermatozoa. On the contrary, the
      preliminary treatment of spermatozoa with CdCl2 or CdSO4 succeeds in reducing the
      fertilization rate of control eggs at concentrations as low as 2 micrograms/ml.
      Cd sulphate appears to be more noxious than Cd chloride. The study of the
      residual motility of sea urchin embryos exposed to either CdCl2 or CdSO4 has
      evidenced a fairly effect at 21 hours after fertilization. On the contrary,
      concentrations of 25 micrograms/ml Cd chloride or Cd sulphate significantly
      affect the motility of 48 hours embryos. Higher levels of cadmium, for example,
      150 or 200 micrograms/ml, completely block the translation of developing
      organisms. In this instance, Cd chloride is more effective than Cd sulphate. In
      addition, a few embryos are affected by malformations and are underdeveloped.
      These results are interpreted on the basis of the inhibitory effect of cadmium on
      the CaCO3 uptake by tissues and structures which physiologically need to be
      calcified in order to develop and function. Further, they give support to the
      predictive significance of the toxicological tests on the sea urchin plutei in
      monitoring environmental hazards.

PMID- 8991827
TI  - [Participation of tachykinins in experimental models of lung damage].
AB  - In the present investigation a possible involvement of tachykinins during sulfur
      dioxide-(SO2) and metabisulfite-(MBS) induced bronchoconstriction, and paraquat
      (PQ)-induced mortality was studied. SO2 (250ppm) inhalation and MBS (3mM)
      perfusion induced a marked decrease of compliance and conductance in the isolated
      and perfused lung. SO2-induced bronchoconstriction was associated with release of
      Calcitonin Gene Related Peptide, suggesting activation of capsaicin sensitive
      sensory nerves. Pretreatment of animals with capsaicin, in order to deplete the
      tachykinin content of sensory nerves, significantly reduced SO2- and MBS-induced
      bronchoconstriction. PQ (25mg/Kg) treatment induced high mortality (75%) after 3
      weeks. Pretreatment with capsaicin significantly protected versus PQ induced
      mortality (25%). The results suggest that tachykinin content in the respiratory
      airways participate to SO2- and MBS-induced bronchoconstriction and PQ mortality.

PMID- 8991829
TI  - [Employment and alcohol: analysis of a clinical casuistic].
AB  - The relationship between alcohol and work was studied in a group of 537 voluntary
      patients (393 male and 144 female) admitted to the department of Medicina del
      Lavoro, Pavia University for alcohol rehabilitation. The highest incidence of
      alcohol abuse was found in non-working subjects (pensioners, unemployed,
      housewives) although the start of excessive drinking takes place after beginning
      a working activity; a cause-effect relationship between these two factors can not
      be clearly determined, however. It is true that the stress provoked by this new
      condition (introduction to the work experience) can, in certain subjects, be a
      contributing factor in alcohol abuse. The increasingly lower age of initiation to
      alcohol reconfirms the need for prevention and instruction even at scholastic
      level. We can deduce how no working condition, low age and low education can
      constitute makers of risk for alcohol abuse.

PMID- 8991828
TI  - [Protective effect on nephropathy and on cataract in the streptozotocin-diabetic
      rat of the vanadium-lazaroid combination].
AB  - Experimental work from our laboratory has confirmed the protective power of
      vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ)
      diabetes. Furthermore, the diabetic cataract too has been partially prevented.
      The protection slightly increased, when vanadium was administered in combination
      with vitamin E. This investigation has introduced a combination of Na3VO4 plus
      the lazaroid U-83836E, a liposoluble antioxidant much more efficacious than
      tocopherol, in order to improve the insufficient protection when vitamin E was
      used. Male Wistar rats, rendered diabetic with STZ, were treated for 12 weeks
      with Na3VO4 in drinking water, U-83836E carried by the food, or both. The most
      significant metabolic parameters (food and fluid intake, diuresis and excreted
      feces) were studied monthly by means of metabolic cages. Body weight, glycemia,
      glycosuria and proteinuria were also recorded. At week 6 and 12 of the treatment,
      the opaqueness of the eye lenses was controlled. Circulation glycosylated
      hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG) and
      fluorescent peroxides were evaluated at the end of the experiment. After the
      first month of treatment U-83836E improved significantly the protective effect of
      vanadate alone on polydipsia and polyuria, but more efficiently on hyperglycemia
      and glycosuria. The further ameliorating effect of the lazaroid was observed also
      on HbA1c, NAG and, most important, on the cataract. In conclusion, these findings
      demonstrate that the lazaroid U-83836E succeeds in further protecting the most
      important symptoms of diabetes treated with vanadate, and that this antioxidant
      acts effectively even when it is administered per os, in a non invasive manner.

PMID- 8991830
TI  - [Medico-legal aspects of the 89/931 act of the EEC].
AB  - The act 391/89 which introduces some substantial news regarding the protection of
      public welfare and the safety of workers, will be taken in account in a next
      future. The A.A. examine these innovations and underline the way they will
      reassert the importance of a concrete application of the principles of primary
      prevention. Moreover, this act will have a large impact on forensic medicine as
      it will allow the acquisition of objective elements to asses the casual nexus
      between occupational exposure and injury, while evaluating the occupational
      etiology of the damage.

PMID- 8991831
TI  - [Reflexions on the aspects characterizing the new INAIL tables regarding
      occupational diseases].
AB  - The AA examine the new Tables for occupational diseases in industry and
      agriculture, which have recently approved with the Presidential Decree n.336,
      april 13, 1994. The main innovations are analysed, like the elimination of some
      too generic terms, which had often allowed contrasting interpretations and a non
      univocal jurisprudence. Other innovative aspects regard the new acquisitions of
      occupational medicine and strengthen, in the new formulation, the principles of
      the presumption of law in establishing a relation of cause and effect.

PMID- 8991832
TI  - [Tumors of the hemolymphopoietic tract and employment in agriculture: a case
      control study carried out in an epidemiologic area in southern Italy].
AB  - To evaluate the role of agricultural exposures in the development of lymphatic
      and haemopoietic tumors a population-based case-referent study has been carried
      out in three health districts of Southern Italy. All incident cases of leukemia,
      lymphoma and myeloma from 1 July 1987 to 30 June 1989, aged 14 years or more,
      have been identified (71 subjects). The control group is formed by subjects with
      other neoplasms. A Job Exposure Matrix, specific to 10 areas, to 6 major crops
      and to 4 calendar periods, was built for assessing pesticide exposure. To date
      100 interviews (to the index subject or to proxies) have been carried out (26
      cases and 74 referents). The odds ratio (OR) of hematologic malignancies for
      agricultural workers was 1.63 [95% Confidence Intervals (95% CI): 0.69-4.34] in
      the whole sample and 6.00 (95% CI: 1.21-25.52) in the female group. Significative
      increased risks have been observed for exposure to DDT and creolin (OR = 4.11;
      95% CI: 1.16-14.55) and, for leukemia, for cattle breeders (OR = 6.38; 95% CI:
      1.46-27.83).

PMID- 8991833
TI  - [Acrylonitrile and chemotaxis: in vitro experiments].
AB  - We have verified that chemotaxis of isolated human polymorphonuclear leukocytes
      (PMN) was a target of in vitro toxicant effect of acrylonitrile (ACN). This
      toxicant induced a significant dose dependent decreasing of chemotaxis with 50%
      inhibition (IC50) occurring at 15 mM. We assume that PMN from workers exposed to
      ACN reacts vivo in a similar way to PMN exposed in vitro to ACN. We propose
      therefore to use chemotaxis assay as a biomarker of early biological effect of
      ACN in workers, since for their monitoring there are so far only internal dose
      indicators but no suitable effect indicators.

PMID- 8991834
TI  - [Laparoscopic "preliminary operation" of ovarian malignancies].

PMID- 8991835
TI  - [Private hospitals for obstetrics--on the development of clinical "obstetric
      science" in Germany in the 19th century].

PMID- 8991836
TI  - [Premature labor and intrauterine infection].

PMID- 8991837
TI  - [New after-care guidelines in breast carcinoma].

PMID- 8991838
TI  - [Medical research at German universities].

PMID- 8991839
TI  - [Structural public health regulation and quality assurance: new impulse for the
      electronic medical record].

PMID- 8991840
TI  - [Complications in 5,000 pelviscopies at the Kiel University Gynecologic Clinic].
AB  - From 1987 to 1991 a total of 5035 pelviscopies were done at the Kiel University
      Hospital of Gynaecology. More than 90% of these were surgical pelviscopies,
      whereas less than 10% were diagnostic procedures only. Serious complications
      requiring laparotomy or repeat pelviscopy or laparotomy within 4 weeks after the
      original procedure, occurred in 2.0% of the cases and slight complications were
      seen in 2.9%. Procedures for acute abdomen or adhesiolysis after multiple
      laparotomies bore the greatest risk of serious complications. Low risk was
      associated with sterilisations, procedures for female sterility, endometriosis or
      tubal pregnancy.

PMID- 8991841
TI  - [Comparison of laparoscopically assisted vaginal hysterectomy with abdominal
      hysterectomy. Technique and results].
AB  - Technique and Results: The aim of this prospective randomised study was to
      compare laparoscopy-assisted vaginal hysterectomy (LAVH, group A) with abdominal
      hysterectomy (abd. HE, group B). Therefore, 35 hysterectomies due to non
      malignant diseases such as uterine fibroma were performed in each group. A rather
      simple technique of LAVH was developed. In respect of the indication for
      hysterectomy, mean duration of operation and the size of the excised uteri there
      were no statistical differences between the two groups. One severe complication
      of haemorrhage was observed after LAVH in a patient suffering from a
      coagulopathy. The requirements for analgesics were significantly lower after LAVH
      compared to abd. HE during the postoperative period. A significantly lower serum
      concentration of the c-reactive protein on the first and third days after
      operation was found in group A. The patients of group A were discharged on the
      average 5 days after operation and 11 days in group B, respectively. Hence LAVH
      should replace abd. HE in most cases with the advantages of shorter
      hospitalisation, minimised requirements for analgesics and cost reduction.

PMID- 8991842
TI  - [Effect of CO2 pneumoperitoneum on intraperitoneal tumor growth in the animal
      model].
AB  - Clinical observations during recent years describe the increased occurrence of
      rapid intraperitoneal metastases and an impairment of prognosis if a malignant
      tumour was operated laparoscopically. It is not known whether the observed
      induction of intraabdominal metastases after laparoscopic surgery in the result
      of an inadequate surgical procedure with spillage of tumour cells into the
      abdominal cavity or whether pneumoperitoneum-induced changes of the peritoneal
      milieu promote tumour growth. An animal model was established to examine the
      effect of a CO2-pneumoperitoneum on the intraperitoneal growth of tumour cells.
      Six week old nude mice were divided into 4 groups of 15 animals each. A CO2
      pneumoperitoneum was induced by a micro-hysteroflator with an intraperitoneal
      pressure of 6 mmHg for 90 minutes in groups 2 and 4. Two different tumour cell
      lines, suspended in 2 ml of Ringer's solution for homogeneous spread of the
      cells, were injected i.p.. The control groups 1 and 3 received the tumour cells
      without pneumoperitoneum induction of a CO2-pneumoperitoneum resulted in an
      increasing seeding rate of tumour cells and provoked a significant increase in
      the number and size of intraabdominal metastases. Laparoscopic surgery of
      malignancies is therefore contraindicated.

PMID- 8991843
TI  - [Addition of ethanol to the distension medium in surgical hysteroscopy as
      screening to prevent "fluid overload". A prospective randomized comparative study
      of ablative versus non-ablative surgical hysteroscopy and different ethanol
      concentration].
AB  - For answering the question at which hysteroscopical procedures an intraoperative
      screening method is necessary to avoid a fluid overload and whether a beginning
      fluid absorption can be diagnosed early by adding ethanol to the distension
      medium, a prospectively randomised comparative study of ablative versus non
      ablative operative hysteroscopy with differing ethanol concentrations was
      performed (n = 120). Purisole (a mannit/sorbit solution) was used a distension
      medium. The measuring parameters (breath alcohol, amount of absorbed fluid,
      haematocrit and haemoglobin values, central venous pressure, heart frequency)
      were intraoperatively determined at 5-minute intervals. The results of the study
      show that with those hysteroscopical procedures during which the endometrium is
      not or only minimally injured (e.g. syneciolysis, hysteroscopic proximal tubal
      catheterisation). Intraoperative screening is not necessary due to the low
      absorbing amounts. With hysteroscopical procedures such as resection of myoma,
      endometrium ablation and septum resection, however, an addition of ethanol of 2%
      to the distension medium has proved useful, because with this method absorption
      amounts of 400 ml and more can be detected by positive values of breath alcohol.
      As the result of a further absorption of fluid, delayed in time compared to the
      first positive value of breath alcohol, there is an increase in central venous
      pressure and hyponatraemia. Intraoperative ethanol monitoring is a non-invasive
      procedure which can be performed during ablative-operative hysteroscopies and has
      no negative influence on the course of the intervention and the general condition
      of the patients.

PMID- 8991844
TI  - [Hysteroscopic treatment of tubal pregnancy by intratubal injection of
      methotrexate].
AB  - The treatment of 3 non-ruptured tubal pregnancies by hysteroscopic intratubal
      injection of methotrexate was reported. In all 3 cases the beta-hCG serum levels
      decreased after injection during clinical, serological and sonographical control.
      In 2 patients the tubes were patent at a later control. In selected cases the
      intratubal administration of methotrexate via hysteroscopy is an alternative
      minimal invasive treatment.

PMID- 8991845
TI  - [Psychiatric and sexual sequelae of hysterectomy--a comparison of different
      surgical methods].
AB  - Comparison of Different Surgical Methods: The cardinal question of this
      prospective longitudinal study was whether different surgical methods of
      hysterectomy correlate with differences in adaptation and in respect of
      psychological as well as sexual consequences. A total of 83 patients were
      investigated immediately prior to surgery as well as 6 weeks later. 61 resp. 58
      patients participated in follow-up investigations 6 months and 1 year following
      surgery. Total hysterectomy was performed vaginally in 16 females, abdominally in
      22 patients. 23 patients underwent subtotal C.I.S.H. hysterectomy. 23 females
      indicated for myoma enucleation formed another group of this study. Besides
      several psychological variables of potential influence such as personality
      characteristics, coping, sexual attitudes and partner satisfaction, the study
      covered psychological as well as physical complaints, life satisfaction and
      differential characteristics of sexual experiences and behaviour longitudinally.
      The results indicate that single subgroups differ from each other in several
      respects. There were no indications of different psychological as well as sexual
      consequences depending on the surgical method. These findings support the view
      that consequences of hysterectomies are more likely to be predicted on the basis
      of psychological traits that existed before the operation, rather than from a
      medico-technical point of view.

PMID- 8991846
TI  - [The so-called "chocolate cyst"--frequently misinterpreted as ovarian
      endometriosis?].
AB  - Limitation of morphological diagnostic and possible misinterpretations are shown
      in a patient with anamnestic ovarian endometriosis. In cases of "chocolate cysts"
      it is necessary to differentiate between ovarian endometriosis and functional
      cysts. Hints for the existence of a functional cyst are an atypical past history
      or perioperative findings. Biochemical analysis of the cyst fluid may lead to a
      correct diagnosis.

PMID- 8991847
TI  - [Circadian blood serotonin and melatonin level in anorexia nervosa patients in
      comparison with normally menstruating women].
AB  - Day and night rhythms of melatonin and serotonin were measured in four female
      anorexia nervosa patients and for comparison in a control group with normal 28
      day menstrual cycle. In the anorexia nervosa group the levels of gonadotropins
      and sexual steroids were distinctly lowered. In the LHRH test the hormonal
      profile showed pubertal to prepubertal patterns of secretion with an only
      moderate increase of LH and distinct shifting of the LH/FSH ratio in direction of
      FSH. For both groups the 24-hour profiles of melatonin and serotonin showed a
      normal cycle, i.e. melatonin had its maximum by night, whereas serotonin in
      contrast displayed its highest values by day. However, in the group of patients
      with anorexia nervosa the maximum of melatonin was on the average 2.1 fold higher
      than that found in the control group, whereas that of serotonin was 1.4 fold
      higher. A close functional coherence between the neurotransmitters melatonin and
      serotonin and the hypothalamic secretion of LHRH is being discussed.

PMID- 8991848
TI  - [Disorder of 17 beta-hydroxysteroid dehydrogenase as the cause of
      hypergonadotropic hypogonadism in 2 siblings with primary amenorrhea].
AB  - We report on two sibs with deficiency of 17 beta-hydroxysteroid dehydrogenase.
      The diagnosis is based on clinical features and endocrine parameters. Main
      symptoms were hypergonadotrophic hypogonadism and male pseudohermaphroditism with
      only slight virilisation. Endocrine investigations including ACTH and hCG
      stimulation revealed reduced levels of estradiol and testosterone, but elevated
      concentrations of DHEAS and androstendione.

PMID- 8991849
TI  - [Results of postpartum Rhesus prophylaxis 1967 to 1990].
AB  - INTRODUCTION: The aim of the study is to analyse the benefit of rh-prophylaxis at
      the Universitats-Frauenklinik Koln from 1967 to 1990. MATERIAL AND METHOD: During
      that period 28,761 births, of whom 2602 were non-sensitized rh-negative mothers
      with a rh-positive child (9.04%), were assessed. 2223 mothers received rh
      prophylaxis, in 379 cases rh-prophylaxis was omitted particularly within the
      first 4 years of the study period, due to a limited provision of anti-D
      immunoglobulines. From 1972 onwards postnatal rh-prophylaxis was omitted in only
      3%. In 14.5% of the 379 women without rh-prophylaxis contamination of the
      maternal circulation system with HbF cells was confirmed by the Kleihauer-Betke
      Test. In 98.4% of the cases rh-prophylaxis was performed postnatally within the
      first 72 hours. RESULTS: During the study period the initial dosage of IgG anti-D
      was set at 55 - 150 microgram i.v. (n = 217) and later increased to 150 - 250
      microgram i.v. (n = 1109) and finally to 300 - 330 microgram i.m. (n = 897).
      After rh-prophylaxis presence of HbF cells in the maternal circulation was found
      in 5.5% of the mothers of group 1, in 2.1% of the second group and in 1.1% of the
      third group. In the group of mothers without rh-prophylaxis 69 had a second
      delivery and rh-sensitsation was found in 7.3% of these cases. Of 537 women
      having received rh-prophylaxis who delivered a second rh-positive child, 9 (1.7%)
      showed rh-sensitisation. of the 352 women with rh-incompatibility 8 (2.3%) had
      already been sentisized during their first pregnancy. CONCLUSIONS: The study
      confirms that postnatal application of anti-D immunoglobulins is effective to a
      great extent but does however not completely exclude rh-sensitisation.
      Furthermore, we recommend the additional prenatal rh-prophylaxis as introduced by
      the German maternity regulations since 1990.

PMID- 8991850
TI  - [HELLP syndrome: recurrence in 4 consecutive pregnancies].
AB  - Recurrence in Four Consecutive Pregnancies in a Patient: We report on the
      recurrence of HELLP-syndrome in four consecutive pregnancies in a patient. The
      observation of recurrence of this rare disorder (0.2-0.8% of all pregnancies) in
      an otherwise healthy patient points to an immunological or genetic predisposition
      for the development of HELLP-syndrome. At the moment there is no possibility to
      identify these patients with a high recurrence risk for HELLP-syndrome before the
      onset of pregnancy.

PMID- 8991851
TI  - [Percutaneous catheter embolization in life threatening obstetrical hemorrhage--a
      case report].
AB  - A case of life-threatening postpartum haemorrhage after Caesarean section is
      reported. The bleeding could finally be stopped by transcatheter embolisation of
      the internal iliac arteries. Our case and literature concerning management of
      obstetric haemorrhage by transcatheter embolisation reveals this method to be
      highly effective, but only slightly invasive and rarely associated with (usually
      minor) complications. The method is considered to be superior to arterial
      ligation.

PMID- 8991852
TI  - Bacterial resistances to toxic metal ions--a review.
AB  - Bacterial plasmids encode resistance systems for toxic metal ions, including Ag+,
      AsO2-, AsO4(3-), Cd2+, Co2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, Sb3+, TeO3(2-),
      Tl+ and Zn2+. The function of most resistance systems is based on the energy
      dependent efflux of toxic ions. Some of the efflux systems are ATPases and others
      are chemiosmotic cation/proton antiporters. The Cd(2+)-resistance ATPase of Gram
      positive bacteria (CadA) is membrane cation pump homologous with other bacterial,
      animal and plant P-type ATPases. CadA has been labeled with 32P from [alpha-32P]
      ATP and drives ATP-dependent Cd2+ (and Zn2+) uptake by inside-out membrane
      vesicles (equivalent to efflux from whole cells). Recently, isolated genes
      defective in the human hereditary diseases of copper metabolism, namely Menkes
      syndrome and Wilson's disease, encode P-type ATPases that are more similar to
      bacterial CadA than to other ATPases from eukaryotes. The arsenic resistance
      efflux system transports arsenite [As(III)], alternatively using either a double
      polypeptide (ArsA and ArsB) ATPase or a single-polypeptide (ArsB) functioning as
      a chemiosmotic transporter. The third gene in the arsenic resistance system,
      arsC, encodes an enzyme that converts intracellular arsenate [As(V)] to arsenite
      [As(III)], the substrate of the efflux system. The triple-polypeptide Czc (Cd2+,
      Zn2+ and Co2+) chemiosmotic efflux pump consists of inner membrane (CzcA), outer
      membrane (CzcC) and membrane-spanning (CzcB) proteins that together transport
      cations from the cytoplasm across the periplasmic space to the outside of the
      cell.

PMID- 8991853
TI  - Acceleration of wound healing in gastric ulcers by local injection of
      neutralising antibody to transforming growth factor beta 1.
AB  - BACKGROUND: Application of neutralising antibodies (NAs) to transforming growth
      factor beta 1 (TGF beta 1) improves wound healing in experimental
      glomerulonephritis and dermal incision wounds. TGF beta 1 has been detected in
      the stomach, but despite the fact that this cytokine plays a central part in
      wound healing no information is available to determine if modulation of the TGF
      beta 1 profile influences the healing of gastric ulcers. This study examines
      gastric ulcer healing in the rat after local injection of NAs to TGF beta 1.
      METHOD: Chronic gastric ulcers were induced in Wistar rats by the application of
      100% acetic acid to the serosal surface of the stomach. Immediately after ulcer
      induction and on day 2, NAs to TGF beta 1 (50 micrograms), TGF beta 1 (50 ng),
      saline or control antibodies (IgG; 50 micrograms) were locally injected into the
      subserosa. Controls received no subserosal injections. Animals were killed on day
      5 or 11, the ulcer area was measured planimetrically, sections were embedded in
      paraffin wax, and stained with trichrome or haematoxylin and eosin. Depth of
      residual ulcer was assessed on day 11 by a scale of 0-3, the percentage of
      connective tissue was determined by a semiquantitative matrix score and
      granulocytes and macrophages in the ulcer bed were also assessed. RESULTS: The
      application of NAs to TGF beta 1 led to a significant acceleration of gastric
      ulcer healing on day 11 (0.6 (SD 0.8) v 3.7 (SD 2.6) mm2), a reduction in
      macrophages (23.7 (SD 22.6) v 38 (26) per 40 x power field) and granulocytes (8.5
      (SD 5.6) v 20 (10) per 40 x power field), fewer histological residual ulcers
      (mean 1 (SD 0.9) v 2 (1.1)), a reduced matrix score, and a regenerative healing
      pattern. Excessive scarring was seen in the TGF beta 1 treated group. CONCLUSION:
      Further treatment of gastric ulcers may induce a new treatment modality by local
      injection of NA to TGF beta 1 in an attempt to accelerate and improve ulcer
      healing.

PMID- 8991854
TI  - Increased rates of duodenal mucosal protein synthesis in vivo in patients with
      untreated coelia disease.
AB  - BACKGROUND AND AIMS: A robust, reproducible method for the measurement of protein
      synthesis in the gastrointestinal mucosa was applied to investigate possible
      differences between the rate of duodenal mucosal protein synthesis in coeliac
      patients and normal control subjects. PATIENTS AND METHODS: Eight patients, means
      (SD) (51 (10) years, 57 (11) kg, 160 (6) cm) with newly diagnosed untreated
      coeliac disease and seven control subjects (48 (11) years, 71.5 (12) kg, 172 (10)
      cm) received primed, continuous, intragastric (IG) and intravenous (i.v.)
      infusions of L-[1-13C]leucine and L-[1-13C]valine after an overnight fast. Distal
      duodenal biopsy specimens were obtained at endoscopy performed after 240 minutes
      of infusion. Protein synthesis was calculated from protein labelling relative to
      intracellular free amino acid enrichment, after appropriate mass spectrometric
      measurements. RESULTS: Rates of duodenal protein synthesis were significantly
      greater in coeliac patients than in control subjects (i.v. tracer, coeliac v
      control, 3.58 (0.45) v 2.26 (0.22)%/h, p< 0.05; IG tracer, 6.25 (0.97) v 2.34
      (0.52)%/h respectively, p < 0.01). The rates of mucosal protein synthesis
      calculated on the basis of the tracer infused via the intragastric route were
      higher in patients with coeliac disease than in control subjects. Tissue
      protein/DNA ratios were significantly reduced in coeliac patients (coeliac v
      control, 9.2 (1.6) mg/micrograms v 13.0 (2.2) mg/micrograms respectively, p <
      0.05) suggesting smaller mucosal cell size in coeliac patients. CONCLUSIONS:
      Despite the villous atrophy and reduced cell size observed in coeliac disease,
      the rates of mucosal protein synthesis are considerably increased. These results
      suggest that a high rate of protein synthesis may be adaptive to a high rate of
      protein breakdown or mucosal cell loss in coeliac patients.

PMID- 8991855
TI  - Effect of a gluten free diet on osteopenia in adults with newly diagnosed coeliac
      disease.
AB  - BACKGROUND/AIMS: Calcium and vitamin D malabsorption in coeliac disease
      predispose to skeletal demineralisation. This study aimed to determine bone
      mineral density in patients studied in the first year after diagnosis of coeliac
      disease, and to detect changes in bone mineral density over the subsequent year.
      METHODS: Lumbar spine and femoral neck bone mineral density was measured in 21
      adults with coeliac disease, diagnosed and started on a gluten free diet during
      the preceding year, with dual energy x ray absorptiometry and repeated after 12
      months. RESULTS: Bone mineral density was significantly lower in patients than in
      paired controls (matched for age and sex), at lumbar spine (0.819 g/cm2 compared
      with 1.021 g/cm2, p < 0.001 Wilcoxon signed rank test) and femoral neck (0.663
      g/cm2 compared with 0.794 g/cm2, p < 0.001). Repeat measurement after 12 months
      demonstrated that patients had a significant gain in bone mineral density at
      lumbar spine (16.6%/year), and femoral neck (15.5%/year, p < 0.002, Wilcoxon
      signed rank test at both sites), whereas no significant change in bone mineral
      density was detected in controls. CONCLUSIONS: Treatment of coeliac disease with
      a gluten free diet is associated with a significant increase in bone mineral
      density, although patients still had lower bone mineral density than controls.

PMID- 8991856
TI  - Prophylactic administration of L-arginine improves the intestinal barrier
      function after mesenteric ischaemia.
AB  - BACKGROUND: Ischaemia/reperfusion (I/R) of the intestine causes mucosal injury
      associated with a high death rate in rats. AIM: To investigate whether nitric
      oxide (NO) might be implicated in the recovery of the intestinal mucosa after
      ischaemic insult. METHODS: Wistar rats were subjected to mesenteric artery
      occlusion for 90 minutes. The animals were given either L-arginine, the substrate
      of NO synthase, or molsidomine, a NO donor. The controls received casein
      hydrolysate. The compounds were administered by gavage 19, 16, and 1.5 hours
      before ischaemia. Mucosal barrier permeability and cGMP content were determined
      24 hours after ischaemia. RESULTS: Survival after I/R was 50% in the control
      group. Animals treated with L-arginine or molsidomine exhibited a higher survival
      rate (70% and 83% respectively). Mucosal barrier permeability was decreased in
      rats receiving L-arginine or molsidomine compared with controls (4.0 (0.9) and
      2.6 (0.6) v 11.2 (1.6) 14C-PEG pmol/segment, p < 0.05). Increased cGMP content
      was seen in the mucosa of the L-arginine group. CONCLUSION: The findings suggest
      that pretreatment with L-arginine or molsidomine ameliorates survival after
      intestinal I/R and improves mucosal barrier function.

PMID- 8991857
TI  - Uptake of yeast (Saccharomyces boulardii) in normal and rotavirus treated
      intestine.
AB  - BACKGROUND: There has recently been a growing interest in the use of the non
      pathogenic yeast Saccharomyces boulardii, in the treatment of gastrointestinal
      disorders, including diarrhoea. The full effects of administration of the yeast
      are not fully understood. AIMS: To investigate the morphological effects of
      inoculated S boulardii on mouse intestinal villi, both in control animals and
      those treated with rotavirus. METHODS: Seven day old BALB/c seronegative mice
      were intubated with either rotavirus (30 microliters orally) or S boulardii (1.5
      g/kg) or both rotavirus and S boulardii administered together. Control animals
      were given saline only. Animals were killed by decapitation 48 hours post
      treatment. The middle region of the small intestine was studied using light
      microscopy and transmission and scanning electron microscopy, including
      backscattered electron imaging. RESULTS: Animals treated with rotavirus with or
      without S boulardii developed severe diarrhoea and showed morphological villous
      changes such as stromal separation and increased epithelial vacuolation.
      Specimens treated with S boulardii contained yeast particles within the mucosal
      tissues. CONCLUSION: The administration of S boulardii did not influence the
      changes produced by rotavirus, but yeast particles appeared to be taken up by the
      villous mucosa, with the predominant route apparently being uptake between
      adjacent epithelial cells.

PMID- 8991858
TI  - Lactose absorption in patients with glucose 6-phosphate dehydrogenase deficiency
      with and without favism.
AB  - BACKGROUND: It has recently been suggested that primary lactase deficiency might
      have been selected for by malaria, as has been previously shown to occur for
      thalasaemia and glucose 6-phosphate dehydrogenase (G6PD) deficiency. AIMS: To
      test this hypothesis, the prevalence of primary lactase deficiency in G6PD
      deficient subjects and in controls from the area of Sassari (Northern Sardinia)
      was determined, which in the past was characterised by an intermediate malarial
      endemicity. SUBJECTS: 70 adult subjects with G6PD deficiency, 34 of whom had a
      past history of favism, and 50 age matched control subjects. METHODS: The
      capacity to absorb lactose was assessed by measuring breath hydrogen production
      after oral administration of lactose (50 g) by a gas chromatographic method.
      RESULTS: Twenty per cent of G6PD deficient subjects with a positive history of
      favism and 22% of G6PD deficient subjects without a positive history of favism
      were lactose absorbers compared with 14% lactose absorbers in the control group.
      The differences were not statistically significant. CONCLUSIONS: These data show
      that the prevalence of primary lactase deficiency in the area of Sassari is
      relatively high, but comparable to that seen in the adult population from another
      area of southern Italy (Naples) where malaria was less endemic.

PMID- 8991859
TI  - Influence of peppermint oil on absorptive and secretory processes in rat small
      intestine.
AB  - BACKGROUND: Peppermint oil is used to relieve the symptoms of irritable bowel
      syndrome, relaxing intestinal smooth muscle by reducing the availability of
      calcium, but its effects on intestinal transport are unknown. AIMS: To determine
      the effect of peppermint oil on intestinal transport processes. METHODS: The
      influence of peppermint oil on intestinal transport was investigated in rat
      jejunum using both intestinal sheets mounted in Ussing chambers and brush border
      membrane vesicles. RESULTS: Mucosal peppermint oil (1 and 5 mg/ml) had no
      significant effect on basal short circuit current, but inhibited the increase
      associated with sodium dependent glucose absorption. The increased short circuit
      current induced by serosal acetylcholine, a reflection of calcium mediated
      electrogenic chloride secretion, was unaffected by mucosal peppermint oil (5
      mg/ml). In contrast, serosal peppermint oil (1 mg/ml) inhibited the response to
      acetylcholine without reducing the effect of mucosal glucose. In brush border
      membrane vesicles active glucose uptake was inhibited by extravesicular
      peppermint oil at concentrations of 0.5 and 1 mg/ml. CONCLUSIONS: Peppermint oil
      in the intestinal lumen inhibits enterocyte glucose uptake via a direct action at
      the brush border membrane. Inhibition of secretion by serosal peppermint oil is
      consistent with a reduced availability of calcium.

PMID- 8991860
TI  - An investigation into the reversibility of the morphological and cytokinetic
      changes seen in the small intestine of riboflavin deficient rats.
AB  - BACKGROUND: Impaired iron handling in riboflavin deficiency is thought to be
      partially a result of significant morphological and cytokinetic changes within
      the small intestine. AIMS: The aim of the study was to find out if the responses
      of the rat small intestine to riboflavin deficiency induced at weaning could be
      reversed upon repletion. SUBJECTS: 48 female weanling Wistar rats were used for
      the purpose of the study. METHODS: Rats were fed a riboflavin deficient diet or a
      complete control diet for a period of five weeks followed by a repletion period
      of up to three weeks. Rats were killed on day 0, 2, 7, or 21 of repletion. The
      duodenum was removed and fixed for subsequent analysis. RESULTS: Five weeks of
      riboflavin deficiency significantly changed the morphology and cytokinetics of
      the duodenum; the changes were not reversed within the 21 day repletion period
      despite biochemical evidence for a correction of the deficiency. CONCLUSIONS: The
      results show that the small intestine cannot readily recover from a period of
      riboflavin deficiency induced at weaning, supporting the notion that the weaning
      period is a critical time for gastrointestinal development and highlighting the
      importance of adequate nutrition during infancy.

PMID- 8991861
TI  - Intestinal permeability in the ileal pouch.
AB  - BACKGROUND: Villous atrophy, mucin changes ('colonic metaplasia'), and chronic
      inflammation occur to varying degrees in all patients with ileal pouchanal
      anastomosis whereas acute inflammation (pouchitis) affects a subgroup of patients
      with prior ulcerative colitis. AIM: To measure epithelial barrier function
      looking for possible functional adaptation in ileal 'pouch' mucosa. PATIENTS:
      Patients with an ileal pouch prior to ileostomy closure (n = 12), functioning
      pouch (n = 14), pouchitis (n = 8), and ulcerative colitis (n = 12) were assessed.
      METHODS: 51Cr-EDTA was administered into the 'pouch' or rectum and urinary
      recovery over 24 hours was taken as an indication of permeability (barrier
      function). Histological analysis of 'pouch' biopsy specimens was undertaken.
      RESULTS: Mucosal permeability is decreased from median 9.4% (range 5.4% to 39.1%)
      to 1.4% (range 0.38% to 2.2%) after ileostomy closure (p < 0.002) with levels
      being negatively correlated with two histological parameters of colonic
      metaplasia-mucin changes (p = 0.03) and villous atrophy (p = 0.05). Pouchitis was
      associated with increased permeability 5.9% (1.9% to 19.5%) compared with healthy
      'pouch' 1.4% (0.35 to 2.2%) (p < 0.006). CONCLUSION: Despite the presence of
      chronic inflammation in the mature 'pouch' functional adaptation with reduced
      permeability occurs in conjunction with colonic metaplasia.

PMID- 8991862
TI  - Effects of dextran sulphate sodium on intestinal epithelial cells and intestinal
      lymphocytes.
AB  - BACKGROUND AND AIMS: The effects of dextran sulphate sodium (DSS) on mouse
      intestinal epithelial cells and intraepithelial lymphocytes were analysed to
      investigate the mechanism by which DSS induces colitis and tumours in mice.
      Cytotoxicity of DSS towards intestinal epithelial cells and intestinal
      intraepithelial lymphocyte hybridomas or fresh intestinal intraepithelial
      lymphocytes seems to have concentration, time, and cell type dependency with
      increasing concentrations and time causing increased cytotoxicity. RESULTS:
      Integrin alpha 4 expression was marginally down regulated by 0.5% of DSS, while
      alpha M290 expression was up regulated. DSS inhibits the binding of 9.1 gamma
      delta cells to both extracellular matrix (ECM) and epithelial cells. Conversely
      at high concentrations it increases binding to all ECM except poly-L-lysine.
      Various cytokines including TGF beta, interleukin 2, and tumour necrosis factor
      alpha as well as prostaglandin alter the expression of the integrin alpha 4 and
      M290 subunits at the cell surface, and also alter the adhesion of 9.1 gamma delta
      cells to epithelial monolayers. The expression of a large number of cell adhesion
      molecules expressed on intraepithelial lymphocytes is affected by a combination
      of the abundant gut cytokine TGF beta and DSS, suggesting that DSS induced
      colitis may ultimately arise from a combination of gut cytokine and DSS. DSS also
      triggers intraepithelial lymphocyte aggregation on all ECM coated plate tested.
      CONCLUSIONS: These data suggest that the potential roles of DSS induced colitis
      may be: (a) direct cytotoxicity; (b) interference with the normal interaction
      between intestinal lymphocytes, epithelial cells, and ECMs; (c) aberrant
      modulation of the expression of the integrin beta 7 receptors, other cell
      receptors, and their functions.

PMID- 8991863
TI  - Prospective controlled trial of duplicated (J) versus quadruplicated (W) pelvic
      ileal reservoirs in restorative proctocolectomy for ulcerative colitis.
AB  - AIMS: A prospective randomised controlled trial was conducted to find out what
      influence the design of the pelvic reservoir had on the functional outcome.
      PATIENTS AND METHODS: Sixty patients received either a duplicated (J) or a
      quadruplicated (W) reservoir, constructed with either 30 or 40 cm of ileum. Each
      patient underwent laboratory tests of anorectal function before and one year
      after operation. RESULTS: One year after operation, 57 patients were available
      for assessment: each had good anal continence, though eight experienced minor
      leakage of mucus, and all were able to defer defecation for more than 15 minutes.
      Median bowel frequency in 24 hours (IQR) in patients with J reservoirs (5 (4-7))
      did not differ significantly from that of patients with W reservoirs (5 (4-6)).
      Likewise, bowel frequency in patients with the smaller (30 cm) reservoirs did not
      differ significantly from bowel frequency in patients with the larger (40 cm)
      reservoirs. However, patients with large W40 reservoirs had the lowest bowel
      frequency of the four groups (median 4 per 24 hours, p = NS). The capacity and
      compliance of the W40 reservoirs were greater than those of the other types of
      reservoir, but the differences were not statistically significant. CONCLUSIONS:
      These findings provide support for the use of a relatively small (30 cm),
      duplicated (J) ileal reservoir, which is simple to construct with linear stapling
      instruments.

PMID- 8991864
TI  - Colorectal adenoma-carcinoma sequence.

PMID- 8991865
TI  - Proximal colonic motility.

PMID- 8991866
TI  - [Effect of antioxidants on the relative risk of coronary heart disease].

PMID- 8991867
TI  - [Adhesion molecules and their role in the inflammatory process].

PMID- 8991869
TI  - Spreading of introduced monogeneans Pseudodactylogyrus anguillae and P. bini
      among eel populations in the Czech Republic.

PMID- 8991868
TI  - Transmission experiments to determine the relationship between Sphaerospora sp.
      from Atlantic salmon, Salmo salar, and Sphaerospora truttae: a revised species
      description for S. truttae.
AB  - Extrasporogonic stages of Sphaerospora sp. from the kidneys of Atlantic salmon
      (Salmo salar L.) were successfully transmitted via intra-peritoneal injection to
      naive Atlantic salmon and brown trout (Salmo trutta L.). Rainbow trout
      (Oncorhynchus mykiss Walbaum) could not be infected in this way. Transmitted
      extrasporogonic stages continued their development to form sporogonic stages and
      mature spores in the kidney tubules. Extrasporogonic stages, sporogonic stages
      and mature spores of the parasite in both experimentally infected hosts were
      morphologically identical to the equivalent stage in naturally infected Atlantic
      salmon, although minor differences were seen in spore dimensions. A farm-based
      exposure experiment confirmed the susceptibility of brown trout to the salmon
      Sphaerospora. These results are consistent with the view that the salmon
      Sphaerospora is Sphaerospora truttae Fischer-Scherl, El-Matbouli et Hoffmann,
      1986. The parasite is redescribed according to the guidelines of Lom and Arthur
      (1989) since details of extrasporogonic stages, the ultrastructure of
      extrasprogonic and sporogonic stage development, and of the parasite's
      epidemiology are known from Atlantic salmon but not from other reports.

PMID- 8991871
TI  - [Physicians as patients--on the problem of the mentally ill physician].
AB  - The phenomenon of mentally ill physicians is hardly noticed in Germany today-a
      fact that possibly indicates a taboo. This investigation is to reveal the
      importance of the subject by referring to the findings of several major studies.
      Epidemiological data turn out to be of little reliability regarding for instance
      the number of impaired physicians with a range between 0.5-46%. Addiction and
      substance abuse can be found in 90% of all cases of mental illness. Increased
      suicide (3-4x), divorce (20x) and addiction rates (according to some authors 30
      100x) in comparison with the average population emphasise the necessity of
      further investigation. These facts imply the question whether doctors are
      mentally more vulnerable than their patients. Special difficulties in treating
      doctor-patients deserve attention as only little is known how appropriate
      "iatrotropic" (psycho-)therapy can be carried out effectively.

PMID- 8991870
TI  - [Ernst Rudin--a Swiss psychiatrist as the leader of Nazi psychiatry--the final
      solution as a goal].
AB  - The study of work and life of the Swiss-German psychiatrist Ernst Rudin, honoured
      up to our time as "father of psychiatric genealogy", lead to different views.
      Rudin early in his life became a racial fanatic, and as a propagandist for the
      purity of the "Germanic people" he constantly demanded preventive coercive
      measures against the reproduction of the mentally ill and other, in the racist's
      view, undesirable persons. With this objective in mind he started his psychiatric
      research. The results of Rudin's monograph about the genetics of dementia precox
      do not withstand scientific criticism but confirmed his preexisting opinions.
      They served however as scientific reasoning for the forced sterilisation by the
      Nazis, for which Rudin's comments were obligatory. The next step, to the
      holocaust of the mentally ill and the undesirable, was not only tacitly agreed
      with by Rudin. Max Weber, Karl Jaspers and others realised at an early time the
      dangers arising from racial hygienics and voiced their warnings in a plain
      language. The surviving victims are still waiting for compensation.

PMID- 8991872
TI  - [Brain infections in father and son and their sequelae--a personal report].
AB  - The author (born 1943) shows which phases of "integration into the society" he
      has undergone since his brain fevers in 1994 and 1958. This paper continues his
      former paper [1], in which are referred the special relations between the author
      and his son (born 1984). As previously in his own case, after his son entered
      school, hardness of hearing was detected which had been caused by a brain
      infection. The paper shows similarities and differences in the pattern of
      symptoms and their social acceptance.

PMID- 8991873
TI  - [Tolerance of ambiguity in endogenous psychoses from the transcultural
      viewpoint].
AB  - This study tries to determine the relationship between intolerance of ambiguity
      and different psychiatric disorders classified according to DSM-III-R criteria in
      two different countries. Inpatients from the psychiatric department of the
      Universidad de Chile and the psychiatric department of the University of
      Heidelberg (Germany) with uniplar, bipolar or schizophrenic disorders, as well as
      normal controls in both cultures completed the Kischkel Intolerance of Ambiguity
      Scale. The group of unipolar depressive inpatients showed significantly higher
      scores in both samples. Among the Chilean schizophrenic patients, differences
      between unipolar and bipolar disorders were seen only in the Chilean sample.
      Differences between unipolar depressive and schizophrenic patients were evident
      in the German sample only. The psychopathological and nosological significance of
      these findings in unipolar depressives is discussed.

PMID- 8991874
TI  - [Nicotine in neuropsychiatric movement disorders].
AB  - Nicotine has various effects in the CNS, especially in dopaminergic and
      cholinergic systems, relevant in pathophysiology of neuropsychiatric movement
      disorders. Nicotine acutely reduce the symptomatology in Parkinson's disease. In
      neuroleptic-induced Parkinsonism (NIP) acute nicotine application induces
      positive changes of symptomatology. Chronic application, however, leads to a
      greater likelihood of NIP. The results concerning tardive dyskinesia are not
      consistent, but nicotine tends to exercise a positive influence on basic
      mechanisms. In the Gilles-de-la-Tourette syndrome nicotine reduces the severity
      and frequency of the tics given in combination with haloperidol.

PMID- 8991875
TI  - [The aortic arch as an embolism source for cerebral infarcts].
AB  - Atherosclerotic plaques in the aortic arch are a potential source of cerebral
      emboli in patients with cryptogenic stroke (Amarenco et al., 1994). We report on
      seven patients with cerebral infarction, who had atherosclerotic plaques in the
      aortic arch, diagnosed by transesophageal echocardiography (TEE). Cardiovascular
      risk factors as hypertension, diabetes, hypercholesterolemia or cigarette smoking
      were found in all cases. Carotid disease was present in four patients, one
      patient had atrial fibrillation with left atrial spontaneous echo contrast, which
      might have been an additional potential embolic source. Intraluminal protrusion
      of the plaques ranged from five to twenty-four millimeters. In conclusion, even
      in patients with carotid or heart disease, the aortic arch may be an important
      source of cerebral emboli. In cases with mobile and pedunculated protruding
      atheromas anticoagulation should be considered.

PMID- 8991876
TI  - Report on the 9th European Workshop on Molecular and Cellular Endocrinology of
      the Testis.

PMID- 8991877
TI  - [A salvage technique for comminuted fractures of the patella].

PMID- 8991878
TI  - [HIV infection and AIDS in Spanish prisons: an impossible challenge for public
      health?].

PMID- 8991879
TI  - [Comparison of knowledge and risk behavior regarding AIDS among HIV+ and HIV-
      inmates at the provincial prison of Granada].
AB  - We have studied at the Provincial Prison of Granada, during the months of July
      and August of 1993 the knowledges of the prison inmates about the transmission of
      the AIDS, measures of prevention, risk behaviors like not use of condoms, use of
      intravenous drugs and sharing syringes. In total, there were 75 human
      immunodeficiency virus infected (HIV+) and 78 not infected (HIV-). The percentage
      of correct answers about transmission were significant, similar to the other
      studies done population in general. For the risk behaviors among HIV+, only 34.7%
      of HIV+, reported the of condoms all the times with their partners. Within the
      HIV+ reported have used intravenous drugs, sometimes 85.3%, sharing syringes only
      43% last time. These data suggest that it is necessary to update the in Jail
      Health Promotion Programmes, in particular stressing the use of condoms and the
      risk sharing syringes by the HIV+ inmates, and informing about the risk of i.v.
      drugs consumption in general.

PMID- 8991880
TI  - [Quality of emergency diagnosis of lesions of external causes requiring
      hospitalization].
AB  - OBJECTIVE: To establish the quality of emergency department diagnoses for those
      patients whose injuries required hospital admission. METHODS: Emergency and
      hospital discharge diagnostics were retrieved for 339 injured patients. Severity
      scores (ISS) were calculated using an automatic conversion procedure (ICDMAP).
      Emergency diagnoses for each patient (grouped into categories) were compared with
      the hospital discharge ones. Quality was analyzed based on accuracy (Percy
      groups) and reliability (percentage of concordance) measurements. Severity scores
      were evaluated using reliability measures (percentage of concordance and
      intraclass correlation coefficient-ICC-). RESULTS: Mean diagnoses per patient
      were 1.1 at the emergency department and 1.4 at hospital discharge. In the
      latter, there were diagnoses in each category except for those more unspecific,
      where there was a reduction. Overall, emergency information showed under
      notification. Severity scores were higher with hospital discharge data. There was
      a 63% percentage of concordance. When grouped into categories, severity scores
      had an ICC of 0.61 (moderate-good). CONCLUSION: Emergency departments are a
      potential good source of information about injury severity even for those
      patients who require hospital admission. Emergency department injury surveillance
      can be very useful in assessing the magnitude and distribution of injury severity
      at the population level. Nevertheless for individual severity assessment, use of
      hospital discharge information is recommended.

PMID- 8991881
TI  - [The population of Catalonia, 1991-2015. A proposal of denominators].
AB  - OBJECTIVES: The purpose of population projection is to have available data in the
      absence of it and to forecast characteristics and structure of the population.
      The objective is to obtain the population of Catalonia by age and sex from 1991
      to 2015. METHODS: The components method was used to obtain the population
      projection with an unique demographic scenario characterized by a low Catalonian
      population aging. The demographic hypotheses assume a stability in the mortality,
      a moderate increase in the fertility with a delay in the schedule and a slight
      net migration. RESULTS: In 2015 the projected population under the combination of
      hypotheses would be decreased in 13.37% for ages less than 15, in 2.27% for ages
      15 through 64 and for people over 65 it would increase in 39.29%. The major
      impact of aging would be observed in female with an increasing in the average of
      age from 39.29 in 1991 to 44.14 in 2015. The projected population would be
      933,540 for the youngest group, 4,004,226 for the adult group and 1,112,732 for
      the aged group. CONCLUSIONS: These results show a progressive aging of the
      Catalonian population due to a reduction of the youngest and an increasing of the
      oldest age groups.

PMID- 8991882
TI  - [Cost-effectiveness analysis of the treatment with enalapril of chronic heart
      failure in Spain].
AB  - The aim of this study is to analyse in terms of cost-effectiveness the
      utilisation of enalapril as part of chronic heart failure therapy in Spain. A
      computer spread sheet based upon the results of the treatment arm of the SOLVD
      (Studies on Left Ventricular Dysfunction) study was used, with costs and
      epidemiologic data referred to Spain. Epidemiologic data are extrapolations from
      either studies performed in other countries or estimates from hospital and
      outpatient clinics utilisation, and economic data are taken from Spanish studies.
      The time horizon of the study was set at four years, and results are referred to
      year 1993. Widespread use of enalapril increases survival in 1.7 months per
      individual or in 5-10,000 years for the whole population. It generates net
      savings for the health system estimated in 1,500 to 3,000 million pesetas, also
      in four years. Using enalapril as part of the standard therapy for chronic heart
      failure generates an increase both in saved years of life and quality of life,
      and is associated with net savings for the health system.

PMID- 8991883
TI  - [Estimate of mortality from occupational cancer and of carcinogen exposure in the
      workplace in Spain in the 90's].
AB  - We estimated the number of cancers attributed to occupational exposures in Spain,
      and examined the prevalence of carcinogenic exposures in the workplace. We used
      population, labour, mortality and morbidity statistics and applied an approach
      used by Doll and Peto for the population of the USA. In men 6% and in women 1% of
      all cancers can be attributed to occupational exposures. Lung cancer accounts for
      62% of all occupational cancers. About 402,346 men and women are employed in
      industries or occupations entailing a well recognised carcinogenic risk. In
      addition, a large but unquantifiable number of workers are employed in various
      other occupations and industries where exposure to carcinogenic chemical or
      physical agents may occur. The identification and control of carcinogenic
      exposures may lead to the prevention of a considerable number of cancers in the
      Spanish adult population.

PMID- 8991884
TI  - [Pharmacologic surveillance and public health surveillance].

PMID- 8991885
TI  - Does cutting nursing staff decrease the quality of care?

PMID- 8991886
TI  - Assessing peripheral arterial disorders in the home: a multidisciplinary clinical
      guide.
AB  - Patients with peripheral vascular diseases (PVD) have venous problems, arterial
      problems, or both. Although several home care clinical guidelines exist for PVD,
      the multidisciplinary clinical guidelines for clients with peripheral arterial
      diseases outlined in this article present new material for nurses and agencies
      who are interested in developing clinical paths for these challenging patients.

PMID- 8991887
TI  - Home care accreditation with the community health accreditation program: part II:
      the process.
AB  - The CHAP accreditation process provides an external, objective marker for the
      clients served by an agency. This marker indicates that the agency has met
      national standards of organizational strength and quality. The process results in
      a detailed analysis of the organization's overall strengths and weaknesses and
      provides expert consultation regarding findings. This ongoing consultative
      relationship between CHAP staff members and/or site visitors and agency
      leadership provides a continued framework for organizational expansion and change
      to meet ever-changing health-care needs.

PMID- 8991889
TI  - Medicare home health agency manual revisions.

PMID- 8991890
TI  - Productivity in home healthcare: part I: assessing nurse effectiveness and
      efficiency.
AB  - Herein described is a profile of the specific knowledge and abilities of the
      productive home care RN that nurse managers can use in maintaining and developing
      an RN staff that is efficient and effective. This article describes the profile
      and shows how it can be used in the hiring process, during orientation, and on a
      day-to-day basis to manage and improve the productivity of current staff members.

PMID- 8991888
TI  - Grieving the loss of the fantasy child.
AB  - Home healthcare nurses are encountering more medically at-risk children. In these
      situations, parenting roles and the responsibilities of the nurse are important.
      The concept of parents' grieving the loss of the "fantasy" child, the purpose of
      various grief feelings, and suggested nursing interventions in this situation are
      explored.

PMID- 8991891
TI  - My patient, my friend: a community health nursing experience.

PMID- 8991892
TI  - Can hospice care be provided to people who live alone?
AB  - A growing number of people live alone; some in need of hospice care. Current
      approaches to providing care include the "patchwork" approach, institutional
      contracts, hospice day care, a demonstration program for people living alone, and
      supported housing. A brief discussion of each is presented, with a closing
      challenge to nursing to provide leadership and bold thinking to meet the changing
      need of these patients.

PMID- 8991893
TI  - Time management strategies for the new home care nurse.

PMID- 8991894
TI  - Foot care in the home: nursing and agency responsibilities.
AB  - Foot care is an integral component of overall patient care provided in the home.
      This article categorizes three levels of foot care that can be provided and gives
      nurses and agencies guidelines for developing policies and procedures that direct
      this type of care.

PMID- 8991895
TI  - On metamorphosis.

PMID- 8991896
TI  - Planning a staff meeting.

PMID- 8991897
TI  - Erratum. Bacillus subtilis spore coat assembly requires cotH gene expression.

PMID- 8991898
TI  - Fetal globin expression in New World monkeys.

PMID- 8991899
TI  - [Evaluation of the cardiovascular impact of hormonal replacement therapy in
      menopausal women].
AB  - Cardiovascular diseases (CVD) are a major cause of female mortality. The
      occurrence of menopause and estrogen deficiency is a well defined risk factor for
      CVD. Both retrospective and prospective epidemiological studies indicate that
      estrogen as well as estrogen-progestin hormone replacement therapy is associated
      with a reduced incidence of mortality and morbidity due to myocardial infarction
      or (probably) to stroke by about 50% without any obvious change in venous
      thromboembolism, when compared to absence of hormone use. A favorable effect of
      estrogens on the lipid profile could explain about 1/3 of this reduction of risk.
      Among other potential non-lipid effects of estrogens associated with a positive
      cardiovascular action, an improvement of insulin secretion together with a
      decrease in insulin resistance have been noted, this effect being however less
      obvious if the progestin used has androgenic properties. An improvement of the
      coagulation-fibrinolysis balance is plausible under treatment, as well as direct
      action of estrogen on the arterial wall (alteration of both endothelium-dependent
      and endothelium-independent factors such as a calcium-antagonist effect), leading
      to an improvement of arterial flow at the coronary, cerebral and peripheral
      levels. Hormone replacement therapy would be a primary and-potentially-secondary
      prevention of cardiovascular diseases. However, large prospective, controlled and
      randomized therapeutic trials that are now underway, are mandatory to
      definitively establish the cardioprotective effect of hormone replacement
      therapy.

PMID- 8991900
TI  - [Evaluation of the preventive role of estro-progestogens and non-hormonal
      therapies in postmenopausal osteoporosis].
AB  - Osteoporosis is a medical, social and economical problem for developed countries.
      Prevention remains the only realistic approach to reduce the burden related to
      this disorder. Primary prevention of osteoporosis is based on efforts to reach a
      maximal peak bone mass at the end of the growth period and, subsequently, at the
      time of menopause. No pharmacological intervention is considered at this stage.
      Biologically, hormone replacement therapy induces a correction of the biochemical
      changes observed in markers of bone remodeling at the time of the menopause. A
      systematic screening of asymptomatic postmenopausal women followed by the
      induction of hormonal replacement therapy in high risk subjects appears to be an
      interesting cost/benefit strategy in terms of reasonable attribution of health
      resources. Nasal administration of calcitonin fully prevents the trabecular bone
      loss observed during the first years of menopause. Notwithstanding, the exact
      dose of nasal calcitonin able to prevent bone loss remains to be fully
      elucidated. Bisphosphonates inhibit bone resorption. Tiludronate prevents
      trabecular postmenopausal bone loss. The use of selectif estrogen receptor
      modulators is based on a possible differential action of these molecules, at the
      level of the estrogenic receptors, depending of the tissue considered. Several
      direct inhibitors of osteoclastic resorption are also under development. Their
      main target is either to prevent the linkage of osteoclasts to the bone matrix or
      to prevent the acidification of bone matrix required to induce the resorption
      process.

PMID- 8991901
TI  - [Hormonal replacement therapy in menopause and the risk of breast cancer].
AB  - Therapeutic trials comparing hormonal replacement therapy (HRT) with a placebo
      are rare and bring up non conclusive results. The last meta-analysis reported
      included 31 non randomized studies. It did not show an increased risk of breast
      cancer in women treated with HRT, compared with untreated women. However, on and
      after the 10th year of use, the risk increased significantly, although only
      slightly. This increase of the risk was restricted to the current users of HRT.
      The three studies published after the meta-analysis showed controversial results,
      and did not allow any conclusion. These wide disparities between the studies have
      highlighted the difficulty in interpreting the results of epidemiological
      studies.

PMID- 8991902
TI  - [Comparative evaluation of oral versus non-oral hormonal treatments in
      menopause].
AB  - Hormonal replacement therapies of postmenopause have proven their beneficial
      effects on symptoms correction and on the decrease in bone loss. As far as
      cardiovascular disease risk is concerned, the epidemiologic trials that suggested
      a protective effect from estrogen therapy considered mainly the oral route.
      However, a positive effect of estradiol has been demonstrated on several
      surrogate markers for cardiovascular risk whether it is administered orally or
      parenterally. As regards the progestins, the type of molecules prescribed appears
      more relevant than the route of administration, the beneficial effects of
      estrogens being unaffected by the non-androgenic progestagens.

PMID- 8991903
TI  - [Evaluation of the risk-benefit ratio of hormonal replacement therapy for
      menopause and susceptible elements in maximizing compliance].
AB  - We recall that the rules of prescription of a hormonal replacement therapy (HRT)
      must involve compliance. The explanations of stopping HRT are multiple: denial of
      menopause, omitting to take the HRT by absence of immediate benefits, poor
      understanding of the interest of long term HRT, side effects and the fear of
      breast cancer. Information associated to the individual assessment of the balance
      between risks and benefits will allow improvement in compliance.

PMID- 8991904
TI  - [Bowel endometriosis. Eight cases of colorectal resection].
AB  - Colo-rectal endometriosis requiring colon resection are reported in 8 patients to
      illustrated the diagnostic and therapeutic problems encountered in the management
      of this uncommon localisation. Pericatamenial or catamenial bowel symptoms
      associated with pelvic genital involvement were encountered in all cases.
      Clinical examination, barium enema and colonoscopy are essential to guide
      surgical management looking for multiple localisations. However their diagnostic
      value is low as endometriosis rarely involves the mucosa. Endosonography appears
      to be very promising in evaluating the depth of infiltration of the bowel. The
      treatment of bowel endometriosis is controversial and varies greatly according to
      the patient's complaints and clinical data. The indications and limits of all
      treatment modalities including abstention, medical, and surgical treatment are
      discussed. From the cases reported we conclude that symptomatic bowel
      endometriosis should be fully excised whenever possible, and the surgical
      procedure should be adapted to the depth of infiltration. A full thickness
      excision or bowel resection is mandatory in patients with deep muscularis
      involvement. These procedures, which are often difficult due to extensive
      fibrosis and adhesions, may be achieved by laparoscopy in selected patients.

PMID- 8991905
TI  - [Uterine leiomyosarcomas: a surprising pathology. Review of the literature. Six
      case reports].
AB  - OBJECTIVE: The aim of this study was to determine the clinical features and
      laboratory tests which define a population with a high risk of leiomyosarcoma.
      METHOD: A retrospective analysis of 660 hysterectomies performed between 1989 and
      1994 was conducted. There were 414 cases of leiomyoma and 6 leiomyosarcomas
      (1.4%). RESULTS: The indication for hysterectomy was complication of
      fibromyomatous uterus in all cases. Diagnosis of leiomyosarcoma was never
      suspected before surgery and the pathology examination. Complimentary
      radiotherapy was given in 2 patients among the 6 with leiomyosarcoma. Mean
      survival was 35 months. There were no cases of recurrence or metastasis. None of
      the laboratory tests performed provided clues to diagnosis. CONCLUSION:
      Physicians should be aware of possible misdiagnosis of a leiomyosarcoma when
      proposing medical treatment of uterine fibroma.

PMID- 8991906
TI  - [Choledochal cyst. Prenatal diagnosis and early neonatal management].
AB  - Cysts of the main bile duct occur rarely. Antenatal diagnosis has improve med
      management. We demonstrate the difficulties in identifying intra-abdominal liquid
      collections at antenatal examinations and discuss the differential diagnosis.
      Certain diagnosis is established when a communication between the bile duct and
      the cyst can be visualized. After sonography confirmation post-natally, early
      surgical cure is required and has radically changed the prognosis of this
      condition.

PMID- 8991907
TI  - [Varicella and pregnancy. Current literature].
AB  - OBJECTIVE: Evaluate of fetal and neonatal risk in cases of maternal varicella or
      zona. METHODS: A review of the literature of varicella occurring during
      pregnancy, including a series of 1,373 cases reported by Enders. RESULTS: The
      role of prenatal diagnosis is discussed as a function of fetal risk, which is
      dependent on gestational age at the time of varicella infection.

PMID- 8991908
TI  - [Evaluation of a classification of newborns and maternity wards in the Loire
      Atlantique department].
AB  - In order to assess the perinatal health policy in a French department in
      comparison with other policies, we performed a prospective transversal survey in
      the Loire-Atlantique for 5 weeks. Newborns were registered according to clinical
      data using the Paris pediatricians classification (classes 1 to 4) and maternity
      wards by number of health personnel and facilities using the American Academy of
      Pediatrician classification (I-III). 1316 newborns were registered. This survey
      showed that the health care organization in maternity wards is rational in the
      Loire-Atlantique for newborns in classes 1 and 4. However, care for newborns in
      classes 2 and 3 could be provided in maternity wards in classes II and III if
      available personnel and equipment is improved.

PMID- 8991909
TI  - [Women with little or no prenatal care during pregnancy. Results of a study of
      twenty departments].
AB  - OBJECTIVES: To estimate the frequency of women who have little or no health care
      during pregnancy, to assess associated perinatal risk, and to identify the
      corresponding risk factors. METHODS: Women who consulted less than 4 times or who
      began consultation during the third trimester were identified in public and
      private maternity units in 20 French departments. These women were compared with
      a sample of women from the same institutions who consulted regularly. RESULTS:
      The percentage of pregnant women with little or no care was 1.1%. Risk of
      premature birth was increased 4-fold compared with women who consulted regularly.
      Women who consulted little were very young, multiparous or living alone with no
      health care insurance. These women stated that the reason for not consulting was
      that their pregnancy was not accepted, financial difficulties and administrative
      problems. CONCLUSION: The lack of regular medical care results from social
      obstacles, especially in foreign born women but is also related to personal
      problems which are difficult to identify and manage.

PMID- 8991910
TI  - [Obstetrical management of triplets. A series of forty five cases].
AB  - OBJECTIVE: To evaluate management of triplet pregnancies. METHODS: A
      retrospective study of 45 triplet pregnancies which occurred spontaneously or
      after assisted reproductive technologies. All were managed by the same
      obstetrical and pediatric team. Obstetrical data were collected. RESULTS: Major
      etiologies were fertility drugs and in vitro methods (66%). Mean maternal age as
      30 years, higher with assisted reproductive technologies (p < 0.05). Risks of
      chorioamniotitis, preeclampsia and anemia were respectively 4.4%, 13.3% and 70%.
      Triplets had a 100% prematurity rate and mean gestational age was 33.6 weeks;
      22.2%, 51.1% and 64.4% delivered before respectively 32, 34 and 35 weeks of
      gestation. Triplet had a 91% cesarean section rate. CONCLUSION: Triplet
      pregnancies present a high risk of prematurity and infertility specialists have
      to be vigilant in the use of fertility drugs. Their management requires early
      reduced maternal physical activity.

PMID- 8991911
TI  - [Infarction and pregnancy. Review of the literature. A case report].
AB  - BUT: Assess risk factors and pathogenesis of myocardial infarction in young women
      and evaluate cardiologic and obstetrical management of myocardial infarction
      during pregnancy as well as assess the prognosis of pregnancy in patients with a
      prior myocardial infarction. METHODS: Fra a personal observation of pregnancy
      after myocardial infarction, we reviewed the literature on two distinct themes:
      myocardial infarction during pregnancy and pregnancy after myocardial infarction.
      RESULTS: Pregnancy was deliberately authorized in a 21-year-old who had
      myocardial infarction 3 years earlier. The pregnancy was uneventful and cesarean
      section with epirual analgesia at 37 weeks gestation delivered a healthy 2,350 g
      boy. Unfortunately the patient died at her home 18 month later. Acardiac cause
      was retained although death due to ventricular rhythm disorder or recurrent
      myocardial infarction could not be confirmed due to lack of an autopsy. The
      prognosis of pregnancies after myocardial infarction would not appear to be
      catastrophic although this case raises some doubts as to whether pregnancy should
      be authorized in these patients. The major difference in mortality according to
      whether the infarction occurs before or during pregnancy would suggest that risk
      might be reduced by a haling period after the infarction. CONCLUSION: It appears
      that pregnancy in women with a prior myocardial infarction would be possible if
      sufficient precautions are taken. All situations increasing cardiac work should
      be avoided. Stress and pain must be avoided during delivery and the post-partum
      period. Intensive cardiological and obstetrical supervision supervision are
      required for correct management of the pregnancy.

PMID- 8991912
TI  - Ultrastructural observations of the tegument of Postorchigenes gymnesicus
      (Digenea: Lecithodendriidae).
AB  - The tegument of Postorchigenes gymnesicus has been studied by scanning and
      transmission electron microscopy. The general body tegument is spinous and
      contains mitochondria, biconcave disc-shaped vesicles bounded by an unitary
      membrane and displaying a protein content, and scarce spherical bodies. The
      tegument covering specialized body regions is aspinous. Few vesicles were evident
      in the tegument covering the suckers and oesophagus, being more abundant in the
      metraterm and cirrus where the tegument is thicker. Laurer's canal has a thick
      tegument with sparse vesicles, mostly arranged close to the apical membrane. A
      direct association was evident between the basal lamina underlying the spines and
      the muscular subtegumental fibres, suggesting a motile character for the spine.

PMID- 8991913
TI  - Parasites of wild houbara bustards in the United Arab Emirates.
AB  - Seven free-living houbara bustards (Chlamydotis undulata macqueeni) wild-caught
      in the United Arab Emirates (UAE) were examined for helminth parasites. Of five
      birds investigated post mortem, one was free of gastrointestinal helminths. Two
      other birds expelled worms following clinical examination and anthelmintic
      treatment. This is the first report of the parasites of free-living, as opposed
      to captive, houbara bastards in the UAE. In infested wild birds, fewer species of
      helminths were recovered than had been found in captive birds and those species
      present had also been found in captive houbaras. Despite heavy worm burdens, the
      infested birds were in good condition. Two species of cestodes (Otiditaenia
      conoideis, Hispaniolepis falsata), two of acanthocephalans (Centrorhynchus
      lancea, Mediorhynchus taeniatus) and two of nematodes (Hartertia rotundata,
      Allodapa sp.) were recovered. Histopathological examination of tissue samples
      from the intestine of three birds revealed no significant pathological changes
      attributable to the presence of parasites but only localized responses at the
      sites of parasite attachment.

PMID- 8991914
TI  - Colonization and establishment of Pomphorhynchus laevis (Acanthocephala) in an
      isolated English river.
AB  - The successful colonization, establishment and spread of Pomphorhynchus laevis in
      a small, isolated, Devon river 128 km from the parasite's nearest focus in Dorset
      was followed over 11 years from 1985. The parasite was first detected in Anguilla
      anguilla and Platichthys flesus in 1988: by 1995 it had attained prevalence
      levels of 22.6% in A. anguilla and 43.6% in P. flesus and also occurred in 100%
      Salmo trutta, 50% Cottus gobio and Noemacheilus barbatulus. As judged by
      prevalence, abundance, proportion of females gravid and weight of gravid females,
      S. trutta was the preferred definitive host although C. gobio was a suitable host
      and may play a role in cycling the parasite: the other three species were
      unsuitable hosts. The intermediate host was the freshwater Gammarus pulex: the
      euryhaline G. zaddachi was not infected. On biological grounds, the P. laevis
      could be assigned to the English freshwater strain and was almost certainly
      introduced to the river by anthropochore stocking of S. trutta from a Dorset
      hatchery. The findings demonstrate conclusively that the English strain of P.
      laevis can colonize and establish in a new locality from which Leuciscus cephalus
      and Barbus barbus, its normal preferred hosts, are absent and use S. trutta
      instead. The results also confirm that P. laevis is a poor natural colonizer and
      appears always to be introduced to new localities by anthropochore transfers of
      fish. The implications of these conclusions for understanding the present
      distribution of P. laevis are discussed and it is considered that they provide
      direct evidence in support of the hypothesis that P. laevis was introduced to
      Ireland from England and subsequently adapted to use of S. trutta and G. duebeni
      there.

PMID- 8991915
TI  - Adherence of carp leucocytes to adults and cercariae of the blood fluke
      Sanguinicola inermis.
AB  - Live adult and cercarial stages of Sanguinicola inermis Plehn, 1905
      (Trematoda:Sanguinicolidae) were maintained in vitro in the presence of carp
      (Cyprinus carpio L.) leucocytes. Cells and parasites were fixed at intervals from
      0.25 to 48 h and examined using light microscopy, SEM and TEM. Within 12 h of
      exposure, leucocytes were found attached to cercariae although, by 24 h, fewer
      cells were found attached to postcercarial, juvenile adult stages that had shed
      their tails. Neutrophils and macrophages were found attached to the damaged
      tegument of cercarie that had not transformed by 48 h. Few cells were attached to
      the tegument of adult flukes that were alive when fixed. However, there was
      extensive tegumental damage and numerous cells were attached to adult flukes that
      had died before fixation. The results are discussed with reference to parasite
      survival within the vascular system of the host.

PMID- 8991916
TI  - Freeze fixation-dehydration as a method of preparation of Gyrodactylus
      (Monogenea) for SEM.
AB  - Freeze fixation-dehydration was used for the first time in the preparation of
      attached Gyrodactylus for SEM viewing. The technique provided instant
      immobilization of specimens before death and negligible shrinkage throughout the
      fixation-dehydration process. Comparisons of sample means of two linear
      measurements of attached opisthaptors showed 20% more shrinkage of Gyrodactylus
      fixed using 10% neutral buffered formalin than those which were freeze fixed.
      Freeze fixation-dehydration was excellent for the study of gross external
      morphology of attached Gyrodactylus. However, the freeze fixation-dehydration
      process may cause disruption of intracellular structural components making
      delicate tissues brittle and more prone to damage during subsequent manipulation.

PMID- 8991917
TI  - Electrophoretic differentiation of soluble egg antigens from Schistosoma mansoni
      isolates using SDS-PAGE.
AB  - In order to detect intraspecies differences among isolates of Schistosoma mansoni
      from different geographical regions, soluble egg antigens (SEAs) of three
      isolates were characterized using SDS-PAGE. SEAs were prepared from eggs of a
      South African (SA), Eastern Caprivian (EC) and Puerto Rican (PR) isolate,
      separated by SDS-PAGE, stained and the molecular masses of constituent
      polypeptides determined. Protein profiles differed for all three isolates with
      the number of polypeptides varying from 25 for the PR isolate to 27 for the EC
      and SA isolates. Molecular masses of the polypeptides fall within the range of
      12.0 kDa to 97.9 kDa. The EC and SA isolates shared ten common polypeptides, the
      PR and SA isolates five and the PR and EC isolates two. Only a 30.8 kDa and a
      12.0 kDa polypeptide were common to all three isolates. These differences may, to
      some extent, account for regional variations in the morbidity of intestinal
      schistosomiasis reported for different geographical isolates of S. mansoni.

PMID- 8991918
TI  - Recent developments in electron holography for phase microscopy.
AB  - This paper reports on the recent remarkable progress made in electron phase
      microscopy, especially due to the development of both a "coherent" field-emission
      electron beam and the related image processing techniques. With these techniques,
      the phase distribution of an electron beam transmitted through a specimen can now
      be measured with a precision of within 1/100 of the electron wavelength to
      observe the thickness distribution of a uniform specimen at the atomic level, the
      magnetic domain structures in a ferromagnetic thin film, and individual vortices
      in a superconducting thin film. Vortices in superconducting thin films have
      become dynamically observable by Lorentz microscopy.

PMID- 8991919
TI  - Do vertebrate thick filaments contain a core? Observations using ultrathin
      sectioning and freeze-etching.
AB  - Transverse ultrathin sections and the freeze-fracture deep-etch method were used
      to study the structure of vertebrate thick filaments. We examined intact frog
      semitendinosus and glycerinated rabbit psoas muscle fibers. In transverse thin
      sections, using standard staining methods, cores were moderately well revealed.
      The cores were particularly distinct when sections were stained with potassium
      permanganate followed by differentiation with bleach. For freeze-etching, the
      specimens were generally fractured transversely, and occasionally obliquely, to
      filament axis, and were then deep-etched and rotary-shadowed. In both transverse
      and oblique images, thick filaments were made up of a central core, surrounded by
      an annular region. Since cores are characteristic of invertebrate thick
      filaments, it is tempting to suggest a similarity. On the other hand, the cores
      observed here seem simplest to interpret as being hollow, as in microtubules.

PMID- 8991920
TI  - Immunoelectron microscopic localization of decorin in aged human corneal and
      scleral stroma.
AB  - Decorin is one of the major proteoglycans in corneal and scleral stroma. Since
      the distribution of decorin in the normal human eye has not been fully
      investigated, we examined its immunoelectron microscopic localization in aged
      human corneal and scleral stroma using anti-decorin antiserum and gold particle
      conjugated secondary antibody. In the corneal stroma, decorin was located on the
      surface of collagen fibrils, on interfibrillar type VI collagen filaments and on
      dark cross-bands of long-spacing collagen which occurred in the aged human
      corneal stroma. In the scleral stroma where the banding pattern of D-periodic
      collagen fibrils was clearly observed, decorin was located on the surface of D
      periodic collagen fibrils, chiefly on the d (XI) and e (IX, X) bands, and also on
      interfibrillar amorphous materials of moderate density which were labeled with
      anti-type VI collagen antiserum.

PMID- 8991921
TI  - Cytochemical localization of photosystem I in relation to differentiation of the
      thylakoid membranes during greening of barley leaves.
AB  - Changes in distribution of photosystem I (PS I) in the developing thylakoid
      membranes of greening barley (Hordeum vulgare L. cv. Amagi-Nijo) chloroplasts
      were studied by a cytochemical method using 3,3'-diaminobenzidine (DAB). The
      activity was detected on the thylakoid of etiochloroplasts after 1 h of greening.
      Stacks of a few thylakoids (thought to be an initiation of grana) appeared at
      about 2-3 h of greening. Until 4 h, the DAB reaction was observed uniformly
      throughout the whole thylakoid system (stroma and grana thylakoids). After 6 h of
      greening, The DAB reaction was detected heterogeneously in the etiochloroplasts;
      more intense on the stroma thylakoid and peripheral grana thylakoid. Further
      illumination led to more distinct heterogeneity of the DAB reaction. Thus,
      redistribution of PS I proceeded differentially after onset of grana formation in
      the developing etiochloroplasts. Measurements of chlorophyll content, light
      saturation of PS I activity and fluorescence emission spectra of greening barley
      leaves suggest that redistribution of PS I may reflect developmental changes in
      assembly of the PS I complex with light-harvesting chlorophyll-protein complex.

PMID- 8991922
TI  - Electron energy-loss spectroscopy study of amorphization process of graphite
      bombarded with hydrogen ions and energetic electrons at low temperatures.
AB  - Structural change of graphite bombarded with hydrogen ions as well as energetic
      electrons is investigated mainly by the EELS (electron energy-loss spectroscopy)
      technique, with a focus on the formation of diamond-like amorphous (DLA) phase at
      low temperatures. The chemical effects of hydrogen ions on the amorphization
      process are examined by comparing the results obtained by hydrogen-ion
      bombardment with those obtained by electron bombardment. The critical
      temperatures for the formation of DLA phase during hydrogen-ion and electron
      bombardments are determined. Finally, a model of the amorphization process of
      graphite during ion-bombardment is presented.

PMID- 8991923
TI  - Application of atomic force microscopy to ultrastructural and histochemical
      studies of fixed and embedded cells.
AB  - Various methods of sample preparation were used to study the cellular
      ultrastructure with an atomic force microscope (AFM). A rather satisfactory fine
      structure of cellular cross section, that was comparable to low to medium
      magnification electron micrographs, was obtained when ultrathin sections of epoxy
      embedded materials cut with a diamond knife were examined by use of a non-contact
      mode. No surface treatment was necessary to image the surface contour of
      ultrathin sections. According to this method, cellular membranes appeared as an
      elevation in contrast to depression of the intercellular space and cytoplasm. The
      chromatin and nucleolus showed an elevated image against the depression of
      nucleoplasm, resulting in the formation of images comparable to those obtained by
      conventional transmission electron microscopy. In the section treated for post
      embedding immunohistochemical reaction, colloidal gold particles larger than 10
      15 nm in diameter could be detected as elevations. By means of Kelvin force probe
      microscopy (KFM), enhancement of the surface potential was detected at exactly
      the same location as topographically detected gold particles. Application of KFM
      is expected to become a valuable tool for novel histochemistry with the use of
      AFM.

PMID- 8991924
TI  - Collagen transformation in abdominal skin of rabbit under continuous wave CO2
      laser irradiation: a transmission electron microscopy study.
AB  - Irradiation of abdominal skin of the rabbit with a continuous-wave CO2 laser beam
      disrupted the collagen fibril into a spiral-like arrangement of thin filaments.
      An altered collagen fibril resulted with the potential for interactions between
      the fibrils. On cross section, the altered fibril shows a central core and an
      irregular limit which seems to interconnect the fibrils. This structure was found
      in a thin layer in the zone with altered collagen, at the boundary of the tissue
      apparently unaffected by the irradiation.

PMID- 8991925
TI  - Observation of ZnO particles grown by electrochemical reaction of Zn.
AB  - The electrochemical reaction of Zn is investigated by scanning electron
      microscopy and transmission electron microscopy. Zn films are used as anodes,
      loaded at DC voltages of 10-200 V in distilled water at 20 degrees C. Zn ions
      diffuse from the anode and are coupled with OH ions to form spindle-like ZnO
      particles of 1-2 microns on the cathode or on a permeable paper barrier placed
      between the anode and cathode. Formless layers, which are composed of fine ZnO
      crystallites of several nanometers or less in size, form on the cathode in the
      water at lower OH ion density before the growth of the spindles. They become
      spindle-shaped after only a few minutes of water bath treatment at 60 degrees C.

PMID- 8991926
TI  - Image forming optics with a common aperture for fast switching between TEM
      magnified image and selected area diffraction.
AB  - Image-forming optics that can switch between a magnified image and its
      diffraction pattern without any movement of aperture is proposed. Both the images
      are alternately taken and are simultaneously shown in a monitor. This type of
      optics is applied to the design of an ultrahigh-voltage electron microscope (H
      3000) and is tested at 100 kV TEM.

PMID- 8991927
TI  - The covering method: an improved negative staining method for ultrathin cryo
      sections of tissue.
AB  - Ultrathin cryo-sections of biological tissues for electron microscopy provide
      numerous advantages in cytochemical and morphological studies. However,
      difficulties still remain in the application of negative staining to cryo
      sections. This paper describes a method for negative staining of cryo-sections by
      covering the grid with a piece of either Collodion or Formvar film. By doing so,
      appropriate amount of staining solution is retained on the grid for positive
      effects. Also, the present method requires only a few seconds to stain the
      ultrathin cryo-sections while previously published methods took up to 10 min.

PMID- 8991928
TI  - Setting of a low price CCD camera on the view window of TEM for printing out
      electron diffraction patterns.
AB  - In order to print out electron diffraction patterns quickly, an industrial CCD
      camera is conveniently set on the view window of an electron microscope. Although
      the observed pattern on the camera is distorted since the view direction has an
      angle of 41.5 degrees from the normal of the screen, however, the printed pattern
      is successfully restored to the correct one by varying the aspect ratio from 3:4
      for the CCD camera to 1:1 for the printer. Note that cos(41.5) = 3/4. The camera
      used has a sensitivity of 1 lux. The aperture ratio of the lens is F 1.4, and the
      focal length is 50 mm.

PMID- 8991929
TI  - Cross-sectional transmission electron microscopy of ZnO tetrapod-like particles.
AB  - ZnO tetrapod-like particles having legs as long as several tens of micrometers
      have been observed by cross-sectional electron microscopy. The specimen is
      prepared by a new method where a photo-resist suspension of the particles fills
      up holes of an electron microscopy grid and is solidified for the subsequent ion
      milling. Electron diffraction and high-resolution electron microscopy of a
      section of a ZnO tetrapod reveal the orientation relationship among its four
      legs, which enables us to discuss on the growth mechanism of these particles.

PMID- 8991930
TI  - A lost son.

PMID- 8991931
TI  - Writer's block.

PMID- 8991932
TI  - Serial analysis of hepatitis B virus core nucleotide sequence of patients with
      acute exacerbation during chronic infection.
AB  - Recent studies suggest that hepatitis B virus (HBV) core region could be an
      immunological target and that amino acid (aa) substitutions are mostly restricted
      to a small segment located in the middle of the core region. We sequenced the
      middle portion of HBV core gene during the course of acute exacerbation of
      chronic hepatitis B, and compared aa variations between the region including
      ideal HLA-A2 binding motifs and the nonbinding region. Five HBeAg+ chronic
      hepatitis patients with subtype adr (three with HLA-A2 and two without HLA-A2)
      were selected and using polymerase chain reaction (PCR) and cloning system, the
      central part of core region (nt 2063 to 2365, 303 bp) was sequenced in sera from
      each patient at three time points; before, at the peak of, and after exacerbation
      of hepatitis. The second set of sera showed higher aa substitution rates in five
      and in three out of five patients compared with those of the first and third
      sera, respectively. No significant difference was found in the aa substitution
      rates for the region with ideal HLA-A2 binding motifs between patients with and
      without HLA-A2. In asymptomatic HBV carriers with persistently normal
      aminotransferase values, alterations of the aa sequence were not observed within
      the same time frame. The results suggest that aa substitutions often occur at
      some particular positions in the middle of HBV core region during acute
      exacerbation of the disease under possible host immune pressures. Furthermore,
      unidentified epitopes appear to exist in the central part of HBV core region and
      HLA-unrestricted lymphocytes may play a role in the immune response of chronic
      HBV carriers.

PMID- 8991933
TI  - Infection with GB virus C in leprous patients in Japan.
AB  - The detection of hepatitis C virus (HCV) in blood donors and patients with acute
      and chronic hepatitis has brought to the fore another virus or viruses which can
      be transmitted parenterally and induce liver disease. The RNA of a candidate
      virus designated GB virus C (GBV-C) was determined by the polymerase chain
      reaction with primers deduced from a helicase-like region in 229 leprous patients
      in Japan. GBV-C RNA was detected in 12 (5.2%) patients, and HCV RNA in 41 (18%).
      Three patients were coinfected with GBV-C and HCV. The nine patients infected
      with GBV-C alone had aminotransferase levels lower than the three patients with
      the mixed infection or the 38 patients infected with HCV only (P < 0.001).
      Sequence comparison within 100 base pairs in the helicase-like region suggested
      that two, three and three patients, respectively, would have been infected with
      three distinct strains of GBV-C. These results indicate that patients with
      leprosy are at increased risk for infection not only with HCV, but also with GBV
      C, and that the infection with GBV-C alone would not induce hepatic injuries as
      severe as HCV infection.

PMID- 8991934
TI  - Mutations in the core promoter region of hepatitis B virus in patients with
      chronic hepatitis B.
AB  - The core promoter region of hepatitis B virus genomes regulates transcription of
      the precore and pregenomic mRNAs encoding hepatitis B e antigen (HBeAg) and core
      antigen that contain target epitopes for cytotoxic T lymphocytes. The prevalence
      and clinical significance of mutations in this region were investigated. DNA was
      extracted from six asymptomatic carriers positive for HBeAg, eight asymptomatic
      carriers positive for an anti-HBe antibody, and 24 patients with chronic liver
      disease. The core promoter and precore regions of hepatitis B virus genomes were
      amplified by polymerase chain reaction, and predominant sequences were determined
      by direct sequencing. Mutations were found in none of the HBeAg-positive
      asymptomatic carriers but in all of the anti-HBe-positive asymptomatic carriers
      and the patients with chronic liver disease. Especially, A to T mutations at
      nucleotide 1762 and G to A mutations at nucleotide 1764 were found in five anti
      HBe-positive asymptomatic carriers, and 22 patients with chronic liver disease.
      These two mutation hot spots were located within binding sites of the nuclear
      factors, and nucleotide 1762 was also involved in the A, T rich sequence that is
      located 28 base pairs upstream of the precore mRNA initiation site. Serum HBeAg
      and DNA polymerase levels were significantly lower in patients with these
      mutations than those without these mutations, and five individuals with these
      mutations were positive for anti-HBe despite the absence of the precore stop
      codon mutation. These mutants may be selected by host immune response to HBeAg
      and/or core antigen.

PMID- 8991935
TI  - Cytotoxic T cell immunity to human cytomegalovirus glycoprotein B.
AB  - Human cytomegalovirus (HCMV) is associated with significant morbidity and
      mortality following immunosuppression and in pregnancy. HCMV infection may be
      accompanied by acute disease but persists asymptomatically. Cytotoxic T
      lymphocytes (CTL) appear to be an important immune effector mechanism in
      maintaining the normal host-virus equilibrium. Glycoprotein B may be an important
      target for future subunit vaccines as it has been found to elicit both
      neutralising antibody and CTL responses. We therefore studied the ability of
      normal asymptomatic HCMV-seropositive individuals and women throughout pregnancy
      to determine the presence of HCMV and gB-specific CTL responses. CTL effector
      cells were induced by stimulation of peripheral blood mononuclear cells (PBMC)
      with AD169 HCMV-infected cells and gB-specific CTL were identified using chromium
      labeled, vac.gB-infected cells. In 7 HCMV-seropositive individuals, HCMV-specific
      CTL were identified. Three of the 7 individuals which lysed HCMV-infected cells
      lysed vac.gB-infected B cells. However, vac.gB-infected autologous fibroblasts,
      which only present MHC class I, were not killed. Using MHC class I single allele
      targets, no specific lytic response was observed, suggesting a MHC class II
      restricted CTL response. Flow cytometric analysis showed the gB-specific effector
      cell phenotype to be CD3+, CD4+, CD8-. In conclusion, a gB-specific CTL lytic
      response was identified in seropositive individuals which in most cases was MHC
      class II-restricted.

PMID- 8991936
TI  - Relevance of RIBA-3 supplementary test to HCV PCR positivity and genotypes for
      HCV confirmation of blood donors.
AB  - HCV antibody screening of 624,910 blood donations resulted in 3,832 samples being
      referred for confirmation. All were tested by RIBA-3 with 2,710 negative, 945
      indeterminate and 177 positive results. HCV RNA was detected by PCR in an average
      of 69.5% of RIBA-3 positives (4 bands 84.1%; 3 bands 74.1%; 2 bands 34.1%) and
      only 0.53% of RIBA-3 indeterminates. Eighty-four percent of samples with a total
      RIBA-3 band intensity score (maximum 16) of > or = 8 were PCR positive compared
      with only 22% of those with a score of < 8. Total mean band intensities for HCV
      genotype 1 samples (n = 65) were 13.2, genotype 2 (n = 17) 11.4 and genotype 3 (n
      = 65) 11.2 with type 1 samples showing greater reactivity with c100 and c33
      antibodies. No PCR positive type 1 samples were found with RIBA-3 total band
      scores less than 8, no PCR positive type 2 samples less than 6, whilst PCR
      positive type 3 samples were found with scores as low as 2. NS5 indeterminates
      were the most common (40.2%) single band pattern but yielded no PCR positive
      samples, followed by c33 (23.3%) with one PCR positive and c100 (20.2%) with one
      PCR positive whilst c22 indeterminates were least common (16.3%) but included
      three PCR positive donors. All five RIBA-3 indeterminate PCR positive donors were
      type 3.

PMID- 8991937
TI  - Comparative study of three PCR assays with antigenaemia and serology for the
      diagnosis of HCMV infection in thoracic transplant recipients.
AB  - Three PCR assays were evaluated for the detection of human cytomegalovirus (HCMV)
      infection in heart and lung transplant recipients in comparison with HCMV
      antigenaemia and serology assay. Polymorphonuclear leucocyte (PMNL) samples taken
      at regular intervals after transplantation were tested for HCMV DNA using primer
      sets homologous to the glycoprotein B (gp58), major immediate early (IE1), and
      structural phosphoprotein (pp150) regions. The detection of HCMV infection at
      various times after transplantation showed all three primer sets to have a
      sensitivity of 100% and a specificity of 92.3% for the detection of HCMV
      infection although overall the gp58 primer set was found to be significantly more
      frequently associated with a positive PCR result than the IE1 (P = 0.0228) and
      pp150 (P = 0.0015) primer sets. The positive PCR result had a positive predictive
      value of 27.8% for HCMV disease. Detection of HCMV infection was first by the PCR
      assay, and significantly before the HCMV antigenaemia assay. Of nine patients who
      received antiviral therapy while PCR positive, only one patient cleared HCMV DNA
      from PMNLs during treatment but became positive again 17 days later. Quantitative
      PCR methodologies may improve the predictive value of PCR for HCMV disease and
      its value for monitoring antiviral therapy.

PMID- 8991938
TI  - Characterization of a new genotype II hepatitis delta virus from Taiwan.
AB  - Three genotypes of HDV, which may be associated with different clinical pictures
      and epidemiological patterns, have been identified. In contrast to Type I and
      Type III HDV, both of which have multiple isolates, Type II HDV so far includes
      only a single isolate (Japan-1) from a low prevalence area (Japan). Recently,
      Type II has been reported to be the predominant genotype in Taiwan, which is also
      a low prevalence area, and is associated with less aggresive disease than Type I.
      However, the sequence and structure of these viruses have not been characterized.
      The complete characterization of a second member (Taiwan-3 isolate) of the Type
      II HDV from Taiwan is reported. These two Type II HDV isolates (Taiwan-3 and
      Japan-1) have 93.8% nucleotide homology and 89.3% amino acid homology,
      respectively. These shared sequences establish the common characteristics of Type
      II viruses. Sequence comparisons of various HDV genotypes show that the
      autocatalytic region of the RNA is relatively conserved between Type I and Type
      II (88.5-95.6% homology) but is significantly divergent in Type III (76.8-80.3%
      homology). The hypervariable region (nucleotides 1602-658) of RNA, however, is
      heterogeneous (64.9-73.0%) among all three genotypes. The delta antigen sequence
      is also very heterogeneous (64.9-73.0%). Most strikingly, the C-terminal sequence
      (19 amino acids) of the large delta antigen is almost completely different in
      each of the three genotypes. The heterogeneity in this region of three HDV
      genotypes may be a basis for their different biological properties, and the
      nucleotide sequences of this region can be used to differentiate the different
      genotypes of HDV. The consensus sequence in the four previously identified
      conserved domains of HDV RNA is defined more precisely.

PMID- 8991939
TI  - Human T-cell lymphotropic virus type-I infection in the severe combined
      immunodeficiency mouse.
AB  - Human T-cell lymphotropic virus type-I (HTLV-I) is the etiologic agent of HTLV-I
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell
      leukemia (ATL). HAM/TSP and ATL occur infrequently among HTLV-I-infected
      individuals, and rarely develop in the same individual. To study host and viral
      factors involved in the induction, tissue tropism, as well as pathogenesis of
      HAM/TSP, peripheral blood lymphocytes (PBL) from 14 patients with HAM/TSP and
      from 9 controls were introduced into severe combined immunodeficiency (SCID) mice
      by intraperitoneal injection. Mice were followed for up to 26 weeks. Human IgG
      was produced from 2 to 14 weeks after reconstitution in all animals. Thirty-two
      of 44 mice (72%) showed circulating human antibody against the major viral
      protein products of HTLV-I. Analysis of viral sequences by polymerase chain
      reaction (PCR) demonstrated HTLV-I sequences in 21/38 (55%) brains and in 7/17
      (41%) spinal cords from HTLV-I-hu SCID mice. No animal had clinical evidence of
      neurological impairment or pathological findings similar to those seen in
      HAM/TSP. Seven mice who received PBL from Epstein Barr virus (EBV)-seropositive
      patients developed an intraperitoneal lymphoma. In 2 mice an infiltration of
      brain by a lymphoblastic tumor of B/T cell type was observed. By PCR, all the
      tumors were EBV-positive; HTLV-I sequences were detected in 5 of them. Our study
      suggests that the HTLV-I-hu-SCID mouse provides a potentially valuable system for
      studying the production, kinetics, and pathogenicity of anti-HTLV-I antibody, and
      may help clarify the interaction of EBV and retroviruses in the development of
      disease.

PMID- 8991940
TI  - Immunoblot detection of antibodies to Toscana virus.
AB  - Sera from patients with sandfly fever caused by Toscana virus (TOSV) infection
      were tested by immunoblot for specific antibody response to TOSV derived from
      infected Vero-E6 cells. The 28 kDa TOSV nucleoprotein (N) was identified as the
      major immunodominant protein recognized by immunoblot. In sera of patients with
      acute TOSV infection, specific antibodies of the IgM, IgA, and IgG class were
      detected. Using sandfly fever virus, serotypes Sicilian (SFSV) and Naples (SFNV),
      as antigens for immunoblot, TOSV antibody-positive sera cross-reacted with the
      corresponding N proteins. These sera reacted for IgM and IgG by SFSV immunoblot,
      and for IgM by SFNV immunoblot. The diagnosis of sandfly fever may be confirmed
      by TOSV immunoblot.

PMID- 8991941
TI  - Absence of extensive genetic heterogeneity of hepatitis C virus in antibody
      negative chronic hepatitis C.
AB  - Hepatitis C virus (HCV) carriers usually have antibodies to HCV; however, there
      are viremic individuals without these antibodies. To investigate whether
      variations of the viral genome are responsible for this discrepancy, the
      nucleotide and deduced amino acid sequences of HCV capsid and nonstructural
      regions obtained from 15 viremic patients were examined. These 15 patients were
      infected with type 1b HCV, and 10 did not have antibody to HCV assayed with
      second-generation tests. The nucleotide homology of the 5 seropositive and 10
      seronegative patients with the HCV prototype sequence were 91.6% and 91.9%,
      respectively, in the capsid region. There was no apparent difference in the
      deduced amino acid sequences between the two groups of patients studied (94% vs.
      95%). The nucleotide and amino acid sequences of a part of the nonstructural
      region 3 also showed similar results. These findings suggest that absence of
      antibodies against both capsid and nonstructural peptides in HCV carriers is not
      caused by genetic heterogeneity of the viral epitopes.

PMID- 8991942
TI  - Nucleotide sequences of the hepatitis C virus core region in patients without
      anti-core antibody.
AB  - Second-generation assays for detection of hepatitis C virus (HCV) infection that
      include reactivity of antibodies to core, NS3, NS4 are used because of their high
      sensitivity. Among these antibodies, anti-core antibody seems to be the most
      sensitive. However, there are some patients without anti-core antibodies,
      although HCV RNA is detectable by reverse transcription-polymerase chain reaction
      and branched DNA assay. The mechanism for the absence of anti-core antibody on
      its own is unclear. We therefore determined the nucleotide and deduced amino acid
      sequences of the core region obtained from two anti-core antibody-negative
      patients with HCV RNA (genotype 1b) and compared them with those of four anti
      core antibody-positive patients and a previously reported sequence. Amino acids
      spanning 1-47, which seemed to exist in major B cell epitopes, were found to be
      completely conserved among these patients. Furthermore, the predictive binding
      motif to HLA DR4 (a.a 81-90) was completely conserved in both of the anti-core
      antibody-negative patients. There were various mutations in the residual amino
      acids spanning 49-108, but specific mutations could not be found in anti-core
      antibody-negative patients. These data indicate that the absence of anti-core
      antibody in two patients is not due to the presence of some formerly unknown
      viral variants, but due to a possible defect in the host's immune system.

PMID- 8991943
TI  - Nucleotide sequence variation in the hypervariable region of the hepatitis C
      virus in the sera of chronic hepatitis C patients undergoing controlled
      interferon-alpha therapy.
AB  - Ten patients with hepatitis C virus (HCV) infection (experimental group) were
      treated with interferon-alpha (IF-alpha). Dosage was six million units per day
      for one week and then three times a week for another six months. Seven HCV
      infected patients (control group) did not receive IF-alpha therapy. The
      hypervariable region (HVR) of HCV in the sera of patients was amplified by
      reverse transcription-polymerase chain reaction (RT-PCR), and the variation of
      amino acid sequence in this region was determined. Serum alanine aminotransferase
      (ALT) activities in five patients treated for six months with IF-alpha fell to
      the normal range, when HCV was not detected in the sera of three patients. The
      nucleotide sequence variation in HVR of HCV in the sera of five patients who
      responded well to the IF-alpha therapy was relatively less than that in another
      five patients who did not respond to IF-alpha therapy and those in the control
      patients. These results indicate that the effectiveness of IF-alpha therapy was
      related to the sequence variation of HVR of HCV. This may have resulted from the
      selection pressure by humoral antibodies directed to HVR of HCV. It is concluded
      that the higher rate of sequence variation in HVR of HCV was compatible with a
      lower degree of effectiveness of IF-alpha therapy.

PMID- 8991944
TI  - Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona
      muricata.
AB  - Bioactivity-directed fractionation of the seeds of Annona muricata L.
      (Annonaceae) resulted in the isolation of five new compounds: cis-annonacin (1),
      cis-annonacin-10-one (2), cis-goniothalamicin (3), arianacin (4), and javoricin
      (5). Three of these (1-3) are among the first cis mono-tetrahydrofuran ring
      acetogenins to be reported. NMR analyses of published model synthetic compounds,
      prepared cyclized formal acetals, and prepared Mosher ester derivatives permitted
      the determinations of absolute stereochemistries. Bioassays of the pure
      compounds, in the brine shrimp test, for the inhibition of crown gall tumors, and
      in a panel of human solid tumor cell lines for cytotoxicity, evaluated relative
      potencies. Compound 1 was selectively cytotoxic to colon adenocarcinoma cells (HT
      29) in which it was 10,000 times the potency of adriamycin.

PMID- 8991945
TI  - Structure and absolute stereochemistry of fusaproliferin, a toxic metabolite from
      Fusarium proliferatum.
AB  - Fusaproliferin is a toxic sesterterpene isolated from Fusarium proliferatum, a
      widespread pathogen of cereals. Its absolute configuration has been determined by
      single crystal X-ray diffraction analysis. Fusaproliferin is considered to be a
      sesterterpene with a new ring skeleton having four C = C double bonds and four
      chiral atoms. The configurations of the four chiral atoms C10, C14, C15, and C19
      are (R), (S), (R), and (S), respectively. In the solid state the macrolide shows
      a concave hydrophobic surface and hydrophilic convex face. The absolute
      configuration of C14 and C15 is the same as that observed for retigeranic acid,
      consistent with fusaproliferin being formed via a sesterterpenic-type
      biosynthetic pathway.

PMID- 8991946
TI  - Five new anthocyanins, ternatins A3, B4, B3, B2, and D2, from Clitoria ternatea
      flowers.
AB  - Five new ternatins 1-5 have been isolated from Clitoria ternatea flowers, and the
      structures have been determined by chemical and spectroscopic methods as
      delphinidin 3-malonylG having 3'-GCG-5'-GCG, 3'-GCG-5'-GC, 3'-GCGCG-5'-GC, 3'
      GCGC-5'-GCG, and 3'-GCGC-5'-GC side chains, respectively, in which G is D-glucose
      and C is p-coumaric acid. Pigment 1 had symmetric 3',5'-side chains. Compounds 3
      and 4 are structural isomers. These ternatins were shown to form an
      intramolecular stacking between the aglycon ring and the 3',5'-side chains in
      solution.

PMID- 8991947
TI  - Cytotoxic amides from the octocoral Telesto riisei.
AB  - Two new acyl derivatives of beta-phenylethylamine, N-(2-phenylethyl)-9-
      oxohexadecacarboxamide (1) and N-(2-phenylethyl)-9-hydroxyhexadecacarboxamide
      (2), and two new tetrahydroxysterols, cholestane-3 beta, 5 alpha,6 beta-26-tetrol
      27-acetate (3) and cholestane-3 beta, 5 alpha, 6 beta-26-tetrol (4), have been
      isolated from the coelenterate Telesto riisei collected in Chuuk, Federated
      States of Micronesia. Structures were determined from spectroscopic data. All new
      compounds were mildly toxic to murine leukemia cells (P-388) in culture.

PMID- 8991948
TI  - Insecticidal neolignans from Piper decurrens.
AB  - 2,3-Dihydro-2-(4'-hydroxyphenyl)-3-methyl-5(E)-propenylbenzofuran (conocarpan)
      (1), 2-(4'-hydroxy-3'-methoxyphenyl)-3-methyl-5(E)- propenylbenzofuran
      (eupomatenoid-5) (2), and 2-(4'- hydroxyphenyl)-3-methyl-5(E)-propenylbenzofuran
      (eupomatenoid-6) (3), three known neolignans found for the first time in a
      species of the Piperaceae, were isolated from Piper decurrens via insecticidal
      bioassay-guided fractionation, along with a small quantity of a new related
      compound, 2,3-dihydro-5-formyl-2-(4'-hydroxyphenyl)-3-methylbenzofuran
      (decurrenal) (4), and 3,7,11,15-tetramethyl-2(E)-hexadecen-1-ol (trans-phytol).

PMID- 8991949
TI  - A new cytotoxic sterol methoxymethyl ether from a deep water marine sponge
      Scleritoderma sp. cf. paccardi.
AB  - 24(R)-Methyl-5 alpha-cholest-7-enyl 3 beta-methoxymethyl ether (1), a new sterol
      ether, has been isolated from a deep-water marine sponge Scleritoderma sp. cf.
      paccardi. Compound 1 exhibited in vitro cytotoxicity against the cultured murine
      P-388 tumor cell line with an IC50 of 2.3 micrograms/mL. The isolation and
      structure elucidation of 1 by NMR spectroscopy is described.

PMID- 8991950
TI  - Halicylindramides D and E, antifungal peptides from the marine sponge
      Halichondria cylindrata.
AB  - Halicylindramides D (1) and E (2) have been isolated from the marine sponge
      Halichondria cylindrata. Halicylindramide D is a tridecapeptide with the N
      terminus blocked by a formyl group and the C-terminus lactonized with a threonine
      residue, while halicylindramide E is a truncated linear peptide with a C-terminal
      amide. Their structures, including absolute stereochemistry, were determined by a
      combination of spectral and chemical methods. Halicylindramide D was antifungal
      against Mortierella ramanniana and cytotoxic against P-388 murine leukemia cells.

PMID- 8991951
TI  - New taxane diterpenoids from the roots of Taxus mairei.
AB  - Two new taxoids, taxumairols A (1) and B (2), have been isolated from extracts of
      the roots of Formosan Taxus mairei (Lemee & Levl.) S. Y. Hu. The structures of 1
      and 2 were identified as 5 alpha, 7 beta, 9 alpha, 10 beta, 13 alpha-pentaacetoxy
      20-(benzoyloxy)- 2 alpha, 4 alpha-dihydroxytax-11-ene and 2 alpha, 5 alpha, 10
      beta,-13 alpha-tetraacetoxy-1 beta, 7 beta, 9 alpha-trihydroxy-4 beta,20-epoxytax
      11-ene, primarily on the basis of 1D- and 2D-NMR techniques including DEPT, COSY,
      and HMBC experiments, as well as chemical correlation with known compounds.
      Taxumairol A (1) exhibited significant cytotoxicities against murine P-388 and
      human KB-16, A-549, and HT-29 tumor cell lines.

PMID- 8991952
TI  - Two new aromatic constitutents from the rootwood of Aeschynomene mimosifolia.
AB  - The rootwood of Aeschynomene mimosifolia Vatke (Leguminosae) has yielded a new
      neoflavonoid, mimosifoliol (1), and an unusual C16-styrylcycloheptenone
      derivative, mimosifolenone (2). The structures of these compounds were determined
      on the basis of spectral analysis. Compound 1 demonstrated weak activity in DNA
      strand scission assay, while compound 2 was found to be inactive. Mimosifoliol
      (1) was inactive toward several human cell lines, while 2 was moderately active
      against the KB cell line.

PMID- 8991953
TI  - Structure elucidation of three triterpene glycosides from the trunk of Argania
      spinosa.
AB  - The structures of three novel saponins from Argania spinosa, named arganines G,
      H, and J, have been elucidated by MS and NMR techniques as 3-O-beta-D
      apiofuranosyl- (1-->4)-beta-D-glucopyranosyl-28-O-beta-D-glucopyranosylbayogenin
      (1), 3-O-beta-D-apiofuranosyl-(1-->4)-beta-D-glucopyranosyl-28-O-alpha- L-
      arabinopyranosylbayogenin (2), and 3-O-beta-D-apiofuranosyl-(1-->4)-beta-D
      glucopyranosyl-28-O- [beta-D-apiofuranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)
      alpha-L - rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl]bayogenin (3),
      respectively.

PMID- 8991954
TI  - Niruriside, a new HIV REV/RRE binding inhibitor from Phyllanthus niruri.
AB  - During the screening of natural products for their ability to inhibit the binding
      of HIV-REV protein to [33P]-labeled RRE RNA, one novel compound, niruriside (1),
      was isolated from the MeOH extract of the dried leaf of Phyllanthus niruri L. by
      bioassay-guided fractionation. The structure of niruriside was determined by
      spectroscopic methods. Niruriside showed specific inhibitory activity against the
      binding of REV protein to RRE RNA with an IC50 value of 3.3 microM; however,
      niruriside did not protect CEM-SS cells from acute HIV infection at
      concentrations up to 260 microM using an XTT dye reduction assay.

PMID- 8991955
TI  - Phytogrowth-inhibitory compounds from Malmea depressa.

PMID- 8991956
TI  - Natural polyphenols (vegetable tannins) as drugs: possible modes of action.

PMID- 8991957
TI  - Squamotacin: an annonaceous acetogenin with cytotoxic selectivity for the human
      prostate tumor cell line (PC-3).
AB  - The bark extracts of Annona squamosa yielded a new bioactive acetogenin,
      squamotacin (1), and the known compound, molvizarin (2), which is new to this
      species. Compound 1 is identical to the potent acetogenin, bullatacin (3), except
      that the adjacent bistetrahydrofuran (THF) rings and their flanking hydroxyls are
      shifted two carbons toward the gamma-lactone ring. Compound 1 showed cytotoxic
      selectively for the human prostate tumor cell line (PC-3), with a potency of over
      100 million times that of Adriamycin.

PMID- 8991958
TI  - Triangulynes A-H and trangulynic acid, new cytotxic polyacetylenes from the
      marine sponge Pellina triangulata.
AB  - Nine new polyacetylenes, triangulynes A-H (1-8) and triangulynic acid (9), have
      been isolated from the marine sponge Pellina triangulata (Oceanapiidae) through
      cytotoxicity-guided fractionation. Structural elucidations and stereochemistry
      assignments were based on chemical and spectral studies.

PMID- 8991959
TI  - Practical considerations on the use of the Charlson comorbidity index with
      administrative data bases.
AB  - To develop a measure of the burden of comorbid disease from the MED-ECHO data
      base (Quebec), the so-called Charlson index was adapted to International
      Classification of Disease (ICD-9) codes. The resulting comorbidity index was
      applied to the study of inpatient death in 33,940 patients with ischemic heart
      disease. Multiple logistic regression was used to relate inpatient death to its
      predictors, including gender, principal diagnosis, age, and the comorbidity
      index. Various transformations of the comorbidity score were performed, and their
      effect on the predictive accuracy was assessed. The comorbidity index was
      constantly and strongly associated with death. From a statistical viewpoint, the
      best results were obtained when the index was transformed into four dummy
      independent variables (the area under the receiver-operating curve is then 0.87).
      In a validation analysis performed on 1990-1991 MED-ECHO data (36,012 admissions
      with ischemic heart disease), the comorbidity index has the same statistical
      properties. We conclude that the Charlson index may be an efficient approach to
      risk adjustment from administrative data bases, although it should be tested on
      other conditions.

PMID- 8991960
TI  - The iceberg delusion.

PMID- 8991961
TI  - [Use of a stimulated echo sequence in the MRI study of the brain and spine].
AB  - We describe in this paper how the STEAM sequence can be an efficient tool to
      obtain images free of flow artifacts in anatomical situation where the spin echo
      failed. The simplest way to eliminate flow artifacts is to exploit the dephasing
      induced by motion in magnetic field gradients and to reduce to zero the signal
      from moving tissues. This can be achieve by increasing the time elapsed between
      the spin excitation and the signal observed. Because of T2 relaxation, such an
      increase results in a signal decrease when the spin echo sequence is used. The
      STEAM sequence has the unique property that the time elapsed between observation
      and excitation can be increased without change in T2 value and so allows a good
      suppression of signals from the moving spins with short TE. Our results
      demonstrate that, although the stimulated echo intensity is only half that of a
      spin echo taken at the same read out time, the advantages of STEAM imaging can
      compensate for this partial loss in signal to noise in some particular clinical
      situations. The influence of mixing time on contrast has been evaluated using
      thoracic spine imaging and it has been shown that contrast between spine and CSF
      can be significantly improved (+ 60%) when TM is increased (from 17 ms to 50 ms).
      In the same time, the contrast between spine and fat issue decreases (40%). This
      last effect facilitates the adjustment of contrast window. Suppression of motion
      artifacts has first been evaluated with thoracic spine imaging, using a whole
      body coil. Suppression of artifacts was better than that obtained with a flow
      compensated spin echo sequence, especially in the case of kyphotic patients when
      a presaturation band was inefficient. In a second step suppression of motion
      artifacts has been evaluated from posterior fossa examination after injection of
      a paramagnetic contrast agent. The images obtained with the stimulated echo
      sequence show a dramatic reduction of signal from blood in the lateral sinus, and
      therefore an increase of quality by elimination of motion artifacts.

PMID- 8991962
TI  - [Diagnosis of a post-thrombophlebitic dural fistula using MR angiography].
AB  - We report a case in which MRA made it possible to diagnose a dural arteriovenous
      fistula and thrombophlebitis in a 23-year old woman. 2D TOF MRA is the usual
      technique in the diagnosis of thrombophlebitis. Our experience shows the limits
      of 2D TOF since the increased signal intensity in the sinus could simulate a
      normal flow, and we describe the advantages of MR subtraction angiography. In our
      study, 3D TOF MRA showed the dural arteriovenous fistula, its location near the
      right transverse sinus and some of the feeding vessels: tentorial branch of the
      internal carotid artery and meningeal branch of the right occipital artery. 3D
      TOF MRA provides the diagnosis of dural arteriovenous fistula, but it cannot
      replace the plain angiography performed before endovascular or surgical
      treatment.

PMID- 8991963
TI  - [Cerebral vascular accidents due to hydatid embolisms. Apropos of 2 cases].
AB  - Hydatid cysts of the brain are very rare. Exceptionally, signs and symptoms are
      primarily those of acute cerebral ischaemia. Two cases of acute cerebral
      ischaemia are reported in a 21 year old and 40 year old women. A computed
      tomographic scan revealed a middle cerebral artery (MCA) infarct and an abrupt
      cutoff of the MCA at cerebral angiography. A few months later, a CT scan showed
      cysts in the territory of the infarct. Hydatid cysts were also found in multiple
      viscera, particularly in the heart. These two observations and some cases
      reported in the literature suggested that the myocardial cyst may have ruptured
      into the ventricular cavity, resulting in widespread intravascular dissemination
      of embryo and causing an acute cerebral infarction. The interest of these cases
      lies in the rarity of an acute cerebral ischaemia due to hydatid cyst embolism,
      and in the early diagnosis of cardiac cysts in young patients.

PMID- 8991964
TI  - Society of Oral Physiology Store Kro Group 19th biennial meeting. Edinburgh,
      Scotland, 11-14 May 1995. Abstracts.

PMID- 8991965
TI  - Precursors, mediators and problem drinking: path analytic models for men and
      women.
AB  - Direct and mediating effects of mechanisms hypothesized to account for the
      association between parental problem drinking and later problem drinking by
      offspring were investigated. Specifically, a "negative affect" submodel was
      proposed in which family environment, self-esteem, alienation, likelihood of
      attaining valued goals, psychopathology, and drinking motives would all mediate
      the parental-problem-drinking to offspring-problem-drinking relationship.
      Subjects were 350 female and 300 male, eighteen to twenty-three year-old
      undergraduates. Multivariate analyses of variance revealed differences in a
      majority of study variables between subjects with and without a family history of
      parental problem drinking. Structural equation modeling identified associations
      separately for paternal and maternal problem drinking and offspring alcohol use.
      Direct and mediating effects were tested with path analysis separately for male
      and female respondents. Both parents' drinking affected later problematic alcohol
      use by offspring. The opposite-sexed parents' drinking had a more negative
      influence on subjects' self-perception. For both men and women, parental problem
      drinking reduced adaptive family functioning, which was subsequently linked to
      problem personality characteristics, more personal drinking motives, and greater
      alcohol involvement. Specific mediating mechanisms varied between models for each
      sex. Implications regarding these models are discussed.

PMID- 8991966
TI  - Illustrating caffeine's pharmacological and expectancy effects utilizing a
      balanced placebo design.
AB  - Caffeine consumption, a ubiquitous cultural phenomenon with significant health
      implications may be governed by some of the same principles which affect other
      drug use [1]. We hypothesized that pharmacological and expectancy effects may be
      two of those principles. A balanced placebo design was used with 100 male
      undergraduates to separate caffeine's active drug effects from the expectancy of
      having consumed caffeine on mood, performance, and physiological measures. The
      manipulation of expectancies was highly effective on subjects' judgments of
      caffeine dosage, regardless of actual caffeine content. As predicted, expectancy
      set and caffeine content appeared equally powerful, and worked additively, to
      affect subjects' ratings of how much the coffee influenced their mood and
      performance. Main effects on systolic and diastolic blood pressure, pulse rate,
      and a fatigue measure were found for caffeine vs. no caffeine groups only.
      Additional increases in diastolic blood pressure for smokers were noted within
      the caffeine-receiving conditions. Results are discussed with heuristic and
      health implications.

PMID- 8991967
TI  - Protective and risk predictors in the development of drug use.
AB  - The authors examined the relationship of two dimensions of the theory of social
      development--vulnerability (predictors, risk factors) and protectivity--in two
      samples, schoolchildren aged ten to fifteen years and addictive drug users. On
      the basis of the Hirschi model of protective factors, they found that the most
      important protective factors (attachment, commitment, involvement, belief) act
      against substance use. A surprising finding was that among the predictors of the
      addicts some forms of escape from the family act against the development of drug
      use, that is, they can be regarded as a protective predictor. The findings of the
      study draw attention to the complexity of the vulnerability-protectivity
      relationship and to the need for further research.

PMID- 8991968
TI  - Home alone: is it a risk factor for middle school youth and drug use?
AB  - This study examined the relationship between middle school/junior high student
      latchkey status and early experimentation and use of alcohol, tobacco, and other
      drugs. Students were queried about the frequency (number of times per week) and
      quantity (number of hours per day) of unsupervised after school days in an
      average week. Questions were also asked regarding their experiences with
      "gateway" drugs, inhalants, and steroids. Chi square analysis was used to test
      the strength of association. The results of this study indicated that latchkey
      youth (LKY) who were home alone two or more days per week were four times more
      likely to have gotten drunk in the past month than those youth who had parental
      supervision five or more times a week. Also, significant differences were
      observed for LKY with respect to cigarette smoking, inhalants, and marijuana use.
      Other findings and demographic variables were discussed as they pertain to LKY as
      well as suggested strategies for healthy self-care alternatives.

PMID- 8991969
TI  - Evaluation of a parent child drug education program.
AB  - The purpose of the study was to evaluate the effectiveness of a parent-child drug
      education program. One thousand four hundred and forty-seven fourth, fifth, and
      sixth grade students and 2,036 of their parents participated in the study.
      Results indicated that the program produced changes in the responses of children
      and their parents to questions concerning attitudes, use, perceptions of use, and
      intended use of drugs.

PMID- 8991970
TI  - Students' self-reported substance use by grade level and gender.
AB  - Over 900 students in the rural northwest at the fourth, sixth, eighth, and tenth
      grade levels were surveyed for alcohol and drug use. The survey instrument
      measured self-reported usage of seventeen substances. The descriptive statistical
      results are reported by gender as well as grade-level usage rates. Discussion
      includes targeting drug prevention programs for specific grade and gender levels
      based upon the results.

PMID- 8991971
TI  - Attitude and peer cross pressure: adolescent drug and alcohol use.
AB  - This research uses the concept of cross pressures, a concept created to explain
      political behavior, to predict the frequency of adolescent alcohol, cigarette,
      and drug use. Using a population of eighth, tenth, and twelfth graders from 207
      Michigan public school districts, respondents reported their frequency of
      alcohol, cigarette, and drug use for thirty days and one year prior to the
      survey. They also reported their perception of friends' approval/disapproval of
      substance use, peer pressure to use, and their assessment of risk of use. Cross
      pressure patterns are created from these three variables and used to predict
      frequency of substance use. In addition to descriptive data and associations
      between independent and dependent variables, the findings show the patterns and
      extent of cross pressures to be highly predictive of frequency of substance use.
      The implications for understanding adolescent substance use and for educational
      programs are noted.

PMID- 8991973
TI  - Stem cell transplantation in autoimmune disease.

PMID- 8991972
TI  - Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients.
AB  - The amended (revised) Beck Depression Inventory (BDI-IA; Beck & Steer, 1993b) and
      the Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) were self
      administered to 140 psychiatric outpatients with various psychiatric disorders.
      The coefficient alphas of the BDI-IA and the BDI-II were, respectively, .89 and
      .91. The mean rating for Sadness on the BDI-IA was higher than it was on the BDI
      II, but the mean ratings for Past Failure, Self-Dislike, Change in Sleeping
      Pattern, and Change in Appetite were higher on the BDI-II than they were on the
      BDI-IA. The mean BDI-II total score was approximately 2 points higher than it was
      for the BDI-IA, and the outpatients also endorsed approximately one more symptom
      on the BDI-II than they did on the BDI-IA. The correlations of BDI-IA and BDI-II
      total scores with sex, ethnicity, age, the diagnosis of a mood disorder, and the
      Beck Anxiety Inventory (Beck & Steer, 1993a) were within 1 point of each other
      for the same variables.

PMID- 8991974
TI  - Cyclophosphamide in lupus nephritis.

PMID- 8991975
TI  - Induction of TNF-alpha and proinflammatory secretory phospholipase A2 by
      intravenous administration of CAMPATH-1H in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To test the effect of infusions of CAMPATH-1H on levels of
      proinflammatory secretory phospholipase A2 (sPLA2) and tumor necrosis factor
      alpha (TNF-alpha) in patients with rheumatoid arthritis (RA). METHODS: Two
      patients with RA were infused with CAMPATH-1H; extracellular nonpancreatic sPLA2
      activity was tested using radiolabelled E. coli membrane phospholipid, and
      circulating TNF-alpha levels were tested by ultrasensitive immunoassay. RESULTS:
      Circulating TNF-alpha began to rise within the first 2 h after infusion, reaching
      > 1000-fold values compared to preinfusion levels. Circulating sPLA2 activity
      began to rise a few hours after the start of infusion and reached extremely high
      values in 12 h, concomitant with fever and hypotension. The activity of sPLA2
      decreased to pretreatment values in 3-18 days after infusion. CONCLUSION: The
      mechanism leading to the increase of TNF-alpha and hyperphospholipasemia A2 has
      not been elucidated. It is possible that CAMPATH-1H activates cells that
      synthesize and release TNF-alpha and sPLA2, and/or that it induces interleukin 2
      release, which in turn activates TNF-alpha, with subsequent release of sPLA2.

PMID- 8991976
TI  - Costimulatory activity of human synovial fibroblasts.
AB  - T cell activation initiated via the CD3/TCR complex requires signals provided by
      the interaction between costimulatory receptors on T cells and their
      corresponding ligands on accessory cells. Human dermal fibroblasts are reported
      to be deficient in this costimulatory activity and normally cannot serve as
      accessory cells for activation of resting T cells. We examined the contribution
      of human synovial fibroblasts to costimulatory activity for resting T cells.
      METHODS: Synovial fibroblast, dermal fibroblast, and umbilical cord endothelial
      cell cultures were established. These cell lines were co-cultured with purified
      peripheral T cells; and T cell activation was assayed using 3H-thymidine.
      RESULTS: Culturing resting T cells with synovial fibroblasts resulted in T cell
      proliferation with either mitogenic (periodate) or alloantigenic stimulation.
      This activation was dependent on the addition of interleukin 1 and/or gamma
      interferon. CONCLUSION: In contrast to dermal fibroblasts, synovial fibroblasts
      are able to provide costimulatory activity for activation of resting T cells.

PMID- 8991977
TI  - Elevation in anti-Proteus antibodies in patients with rheumatoid arthritis from
      Bermuda and England.
AB  - OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) from
      Bermuda and England have an increased anti-Proteus antibody titer when compared
      to healthy Bermudian and English controls, and to ascertain whether any increase
      in antibody titer is specific by testing 4 other microbes, Escherichia coli and 3
      normal anaerobic bowel bacteria. METHODS: Antibody titers were measured by ELISA
      and indirect immunofluorescence (IIFA) under coded conditions. RESULTS: Elevated
      titers of anti-Proteus antibodies were demonstrated in 34 patients with active RA
      from Bermuda when compared to 33 healthy Bermudian controls by ELISA (p < 0.001)
      and IIFA (p < 0.001). An elevation of anti-Proteus antibodies was also observed
      in 34 patients with RA from England when compared to 30 healthy English controls
      again by ELISA (p < 0.001). A similar antibody elevation in 31 patients with RA
      from England was observed when compared to 30 healthy controls when measured by
      IIFA (p < 0.001). However, there was no significant elevation in antibody titers
      against E. coli or the 3 normal bowel flora isolates in the patients with RA from
      both countries compared to their respective controls, when measured by ELISA.
      CONCLUSION: A specific elevation in the immune response to Proteus mirabilis has
      been demonstrated in patients with RA from both Bermuda and England. However,
      this study cannot distinguish between antibody association with disease per se
      and association with disease activity. The role of Proteus in RA and the effect
      of anti-Proteus therapy in patients with RA merits further study.

PMID- 8991978
TI  - Dysregulation of the hypothalamo-pituitary axis in rheumatoid arthritis.
AB  - OBJECTIVE: To study the dynamic response of the hypothalamo-pituitary- adrenal
      axis and of prolactin (PRL) pituitary secretion in rheumatoid arthritis (RA).
      METHODS: We performed a cortisol releasing hormone (CRH) provocation test
      followed by determination of adrenocorticotropin hormone (ACTH), beta-endorphin,
      and cortisol concentration, and then a thyrotropin releasing hormone (TRH)
      provocation test followed by assessment of PRL pituitary secretion in 10 patients
      with RA and 5 control subjects. All were women under 40 years of age. Hormone
      concentrations were assessed by radioimmunoassay. RESULTS: Basal PRL cortisol,
      and ACTH concentrations were similar in patients with RA and controls. We
      observed a dissociation between the pituitary secretion of beta-endorphin and of
      ACTH in response to CRH in RA. The ACTH peak and total ACTH production (area
      under the curve, AUC) were similar in the 2 groups. In contrast, basal beta
      endorphin was increased in RA (12.6 +/- 1.41 vs 8.29 +/- 0.144 pg/ml), and the
      response upregulated (AUC: 83,080 +/- 12,000 vs 54,200 +/- 2400) after CRH
      compared to controls (p < 0.05). Cortisol adrenal response curve was blunted, but
      did not reach statistical significance. In contrast, the PRL response to TRH was
      increased at 120 and 150 min (3461 +/- 303 vs 1897 +/- 520 muIU/ml)(p < 0.01) in
      patients with RA, independent of disease activity. CONCLUSION: We observed
      upregulated pituitary PRL secretion in RA, and a dissociation of ACTH stress. The
      implication concerning the neuroendocrine system in the chronic immune response
      in RA is discussed.

PMID- 8991979
TI  - The assessment of functional status in rheumatoid arthritis: a cross cultural,
      longitudinal comparison of the Health Assessment Questionnaire and the Groningen
      Activity Restriction Scale.
AB  - OBJECTIVE: To compare a disease specific measure of functional status, the Health
      Assessment Questionnaire (HAQ) with a generic measure of functional status, the
      Groningen Activity Restriction Scale (GARS) in a cross cultural and longitudinal
      setting. Besides the comparison of psychometric properties, sex differences were
      also studied. METHODS: In a sample of 634 patients with rheumatoid arthritis (RA)
      (290 from The Netherlands, 116 from France, 228 from Norway), the psychometric
      properties (Cronbach's alpha and rho) of the GARS and the HAQ were compared among
      countries. The sensitivity for change between T1 and T2 was tested by means of
      the standardized response mean for a one year followup; furthermore, the relative
      efficiency of both instruments was computed. A t test was used to trace sex
      differences. RESULTS: The psychometric properties of both the HAQ and the GARS
      were very good. Both form unidimensional scales of hierarchically ordered items;
      alpha and rho are > 0.91 for both instruments. For patients who improved between
      T1 and T2, measured by the Ritchie Articular Index, the standardized response
      mean of the HAQ and the GARS were moderate, whereas for patients who worsened,
      the standardized response means were small. The results based on the relative
      efficiency were ambiguous. Furthermore, the mean score for women on the HAQ was
      0.25 higher in contrast to scores for men. The GARS did not yield different
      scores for women and men. CONCLUSION: The internal consistency of the GARS and
      the HAQ are comparable. The HAQ has yielded different results for women and men.
      Therefore, when the HAQ is used, sex differences should be taken into account.
      With respect to sensitivity to change, the GARS and the HAQ obtained much better
      results for patients who improved in contrast to patients who worsened. The GARS
      was found to be more sensitive to change for patients who improved.

PMID- 8991980
TI  - Risk factors for early wound complications after orthopedic surgery for
      rheumatoid arthritis.
AB  - OBJECTIVE: To identify risk factors for the occurrence of early wound
      complications following orthopedic surgery in patients with rheumatoid arthritis
      (RA). METHODS: We reviewed records of patients with RA undergoing joint surgery
      to identify predictors of the following early postoperative surgical outcomes:
      (1) prolonged drainage; (2) wound cellulitis; (3) wound dehiscence; (4) suture
      abscess; and (5) superficial or deep wound infection. RESULTS: During the study,
      204 patients with RA underwent 119 total knee replacements, 105 total hip
      replacements and 143 procedures of other joints, for a total of 367 orthopedic
      surgeries. A total of 57 complications were observed (15.9%) of which 26 were
      considered major (7%). Of the 230 total arthroplasties of the hip, knee, shoulder
      or elbow, 3 were followed by early deep wound infections (1.3%). In univariate
      analysis, factors significantly related to the occurrence of complications
      included Hispanic ethnicity [relative risk (RR) 1.43, 95% confidence interval
      (CI) 1.16 to 1.78]. and preoperative use of azathioprine (RR 2.13, 95% CI 1.04 to
      4.37). Complications were less frequent among patients given methotrexate, but
      the differences was not significant. Operative blood loss was inversely related
      to the occurrence of complications. In the multivariate model, the only
      significant predictors of complications were Hispanic ethnicity (RR 2.86, 95% CI
      1.43 to 5.56) and operative blood loss (RR 0.50/liter lost, 95% CI 0.29 to 0.86).
      CONCLUSIONS: We were unable to demonstrate an independent effect of antirheumatic
      therapy at the time of surgery on the occurrence of postoperative wound
      complications. Our study suggests that patients with RA of Hispanic ethnicity may
      be at increased risk of developing postoperative wound complications following
      orthopedic surgery. Further study is necessary to explain the mechanism of
      increased complications in this population.

PMID- 8991981
TI  - Sharing of MHC haplotypes among patients with systemic lupus erythematosus from
      unrelated Caucasian multicase families: disease association with the extended
      haplotype [HLA-B8, SC01, DR17].
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease
      often clustered in families. We investigated the association between MHC
      haplotypes and SLE in multicase Caucasian families. METHODS: Ten consecutive
      families with 2 or more patients with SLE, in total 27 patients among 66
      individuals, were studied. MHC haplotypes were determined by typing for HLA-A, B,
      C, DR, and DQ by serological and DNA methods. Complotypes were determined by
      protein typing and C4 gene polymorphism by DNA analysis. RESULTS: Fifty-four
      independent MHC haplotypes were found. Ten of the 31 haplotypes in the patients
      with SLE were examples of the extended haplotype [HLA-B8,SC01,DR17]. Six of these
      were found in 2 or more patients with SLE within the same family. All the 14 SLE
      sib-pairs in the families shared at least one haplotype and in 9 of the sib-pairs
      the shared haplotype was [HLA-B8,SCO1,DR17]. Three SLE associated haplotypes were
      [HLA-B7,SC31,DR15]. Four of the 27 patients with SLE were C4A deficient. Two C2
      deficient siblings were homozygous for the haplotype [HLA-B18,S042,DR15].
      CONCLUSION: We demonstrate that a very limited number of MHC haplotypes are
      associated with familial SLE. The haplotype [HLA-B8,SCO1,DR17] was closely
      related with the disease. There was no evidence suggesting familial SLE
      constitutes a disease subset. Determination of MHC haplotypes in multicase
      families is of value for assessment of disease susceptibility.

PMID- 8991982
TI  - A study of the major histocompatibility complex in a Caucasian family with
      multiple cases of systemic lupus erythematosus: association with the C4AQ0
      phenotype.
AB  - OBJECTIVE: In an epidemiological survey of systemic lupus erythematosus (SLE) in
      Iceland several families with multiple cases were identified. In one family, 35
      individuals (family members and spouses) in 3 generations were studied
      clinically, tested for autoantibody formation, and typed for HLA and toxicity
      complement phenotypes. METHODS: Typing for HLA-A, B, C, DR, and DQ was performed
      by microlymphocytotoxic assay. In selected samples HLA-DR typing by polymerase
      chain reaction amplification with sequence specific primers was performed. C4
      allotypes were defined by agarose gel protein electrophoresis followed by
      immunofixation with goat antisera. RESULTS: Five family members fulfilled 4 or
      more criteria for SLE. Additionally, 5 family members had clinical manifestations
      or positive serology but did not fulfill 4 ARA criteria. The mean age at onset of
      symptoms was 22 yrs (8-40). Other autoimmune diseases were not documented in
      family members. C4A null seemed to be highly associated with disease in this
      family. All except one patient with SLE and all those with clinical
      manifestations and positive serology had C4A null in the homozygous or
      heterozygous form. The individual with SLE and not carrying C4A null had both HLA
      haplotypes identical. It is noteworthy that there were 5 different C4A null
      bearing haplotypes involved, of which 3 originated from the spouses. CONCLUSION:
      Our results are consistent with the argument that C4A deficiency plays a role in
      the pathogenesis of SLE. There is, however, the possibility of an unidentified
      environmental or another genetic factor being involved.

PMID- 8991983
TI  - Danazol for systemic lupus erythematosus with refractory autoimmune
      thrombocytopenia or Evans' syndrome.
AB  - OBJECTIVE: To determine the efficacy of danazol for refractory autoimmune
      thrombocytopenia or Evans' syndrome complicating systemic lupus erythematosus
      (SLE). METHODS: We studied 16 consecutive patients with SLE and corticosteroid
      refractory autoimmune thrombocytopenia; 3 patients had coexisting autoimmune
      hemolysis (Evans' syndrome). Five patients had undergone splenectomy. Danazol was
      commenced at 200 mg/day, and increased stepwise (maximum 1200 mg/day) until
      benefit or toxicity was observed. After remission the danazol dose was gradually
      reduced to 200-400 mg/day. RESULTS: All 16 patients achieved a complete remission
      (platelet count >100 x 10(9)/l, hematocrit >39%) 2 months after starting danazol
      (range 6 weeks-8 months). Remission persisted during continued danazol therapy
      (mean followup 18.2 months, range 2-49 months). One patient with Evans' syndrome
      required discontinuation of danazol because of jaundice and biopsy proven minimal
      hepatic necrosis: hemolysis recurred after discontinuation of danazol.
      CONCLUSION: Danazol is effective for the treatment of autoimmune thrombocytopenia
      or Evans' syndrome complicating SLE irrespective of splenectomy status. Longer
      followup will be needed to determine whether the remission persists after
      withdrawal of danazol.

PMID- 8991984
TI  - Position 26 of the first domain of the HLA-DQB1 allele in post-silicone implant
      scleroderma.
AB  - OBJECTIVE: To determine whether women with scleroderma (systemic sclerosis, SSc)
      and silicone implants have the same or distinctive immunogenetic findings
      compared to those reported for idiopathic scleroderma. METHODS: In this case
      control study, 9 Caucasian women with SSc and silicone implants (7 breast, 1
      chin, 1 toe) and 128 healthy Caucasian controls were typed for HLA class II
      (DRB1,3,4,5, and DQB1) by DNA polymerase chain reaction (PCR) sequence specific
      oligonucleotide probes (SSOP). RESULTS: All women with SSc had HLA-DQ5 or DQ7
      (DQB1*0301). These 2 alleles have glycine (Gly) or tyrosine (Tyr), and not
      hydrophobic leucine (Leu), at position 26 in the 2nd hypervariable region of the
      DQB1 first domain. The increased frequency of at least one Leu 26 negative allele
      (Gly + or Tyr +) in the women with SSc (100%) compared with controls (73%) was
      not statistically significant. In contrast, the low frequency of one Leu 26+
      allele in the patients (28 vs 57%, p = 0.03, RR = -3.3) and 2 Leu 26+ alleles (0
      vs 35%, p = 0.03, RR = -10.4) was significant. CONCLUSION: The presence of Gly 26
      or Tyr 26 in the HLA-DQB1 first domain in our cases with SSc and silicone
      implants is consistent with immunogenetic findings reported in Caucasian with
      idiopathic SSc anticentromere autoantibodies. Whether all the immunogenetic
      features in SSc associated with silicone implants remain indistinguishable from
      those seen in idiopathic.

PMID- 8991985
TI  - Elevated levels of platelet derived growth factor and transforming growth factor
      beta 1 in bronchoalveolar lavage fluid from patients with scleroderma.
AB  - OBJECTIVE: Systemic sclerosis (scleroderma, SSc) frequently affects the lungs,
      and interstitial pulmonary fibrosis is one of its major complications. The
      pathophysiology of SSc lung disease s poorly understood, but recent studies
      document an inflammatory process resembling that of idiopathic pulmonary fibrosis
      with increased numbers of activated alveolar macrophages and granulocytes in
      bronchoalveolar lavage (BAL) fluid). We determined levels of 2 potentially
      important mediators of fibroproliferative repair in BAL fluid from patients with
      SSc. METHODS: Using Western blot and ELISA techniques we measured levels of
      platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF
      beta in BAL fluid from patients with SSc and healthy controls. The mitogenic
      effect of these cytokines on SSc lung myofibroblasts was determined by
      [3H]thymidine incorporation. RESULTS: SSc BAL fluid contains significantly
      elevated levels of PDGF-AA and PDGF-BB. Where TGF-beta 1 was significantly
      elevated in SSc lavage fluid, the amount of TGF-beta 2 was significantly less
      than that observed in normal lavage fluid. Myofibroblasts cultured from SSc
      lavage fluid exhibited enhanced [3H]thymidine incorporation upon exposure to the
      growth factors present in SSc BAL fluid: PDGF and TGF-beta 1. SSc lung
      myofibroblasts pretreated with TGF-beta 1 exhibited an enhanced mitogenic effect
      upon stimulation by PDGF, due in part to the induction of the PDGF alpha
      receptor. CONCLUSION: Our studies support a role for PDGF and TGF-beta 1 in the
      pathogenesis of SSc lung disease.

PMID- 8991986
TI  - The B7 cross reactive group and spondyloarthropathies: an epidemiological
      approach.
AB  - OBJECTIVE: To study the association between the B7 cross reactive group (B7, B40)
      and spondyloarthropathy (SpA), taking into account patients with atypical
      features. METHODS: We studied the main clinical and paraclinical features of 51
      patients with rheumatoid arthritis, 55 with SpA, 120 with mechanical diseases,
      and 160 with inflammatory rheumatism not fulfilling the diagnostic criteria
      currently used. This descriptive analysis was performed using multiple
      correspondence factorial analysis to identify subgroups among unclassified
      patients and select SpA variants. We compared HLA frequencies among these groups
      versus a control group. RESULTS: We identified a subgroup close to the axial SpA
      and related to B7 (OR:5.91, p = 0.0008), whereas B40 is related to patients close
      to the peripheral SpA. CONCLUSION: B7 is related to axial SpA variants manifested
      by inflammatory low back pain according to Calin's criteria, with either
      extraarticular signs or sacroiliitis. Followup of such patients is required to
      determine whether their disease is a new entity or can be considered SpA.

PMID- 8991987
TI  - Prevalence of antiphospholipid antibodies in patients with ankylosing
      spondylitis.
AB  - OBJECTIVE: To establish the prevalence of antiphospholipid antibodies (aPL) in a
      group of patients with ankylosing spondylitis (AS). The relation of the
      antibodies with different clinical and analytical features was studied. METHODS:
      Eighty-four patients with AS (71 men) and 40 age and sex matched controls were
      studied. aPL determinations included: anticardiolipin antibodies (aCL) of the
      IgM, IgG, and IgA classes, the presence of lupus anticoagulant (LAC), and a false
      positive serologic test for syphilis. Comparisons between variables were done by
      Student t test, Mann-Whitney test and Chi squared test. Correlations between aPL
      and clinical variables were performed by Pearson coefficients. RESULTS: Twenty
      four patients with AS (29%) has positive IgG aCL, compared with only 2 cases in
      the control group (5%) (p < 0.002). There were no differences in other aPL
      determinations between patients and controls. There was no correlation between
      the presence of aCL (IgG, IgM, or IgA) and LAC and the different aspects of the
      disease. Two patients fulfilled the criteria for antiphospholipid syndrome.
      CONCLUSION: Our results indicate the presence of IgG aCL in patients with AS
      higher than in the normal population but their relation with thrombosis and other
      systemic manifestations seems weak.

PMID- 8991988
TI  - Antibodies to phospholipid-free beta 2-glycoprotein-I in patients with primary
      antiphospholipid syndrome.
AB  - OBJECTIVE: To investigate serum anti-beta 2-glycoprotein-I antibodies (a beta 2
      GP-I) in patients with primary antiphospholipid syndrome (APS). METHODS: We
      studied a beta 2 GP-I by Western blot, dot blot, and ELISA in the sera of 15
      patients with primary APS with high titers of immunoglobulin G (IgG) and/or
      immunoglobulin M (IgM) anticardiolipin antibodies (aCL) at the time of study and
      compared findings with the sera of 13 aCL positive patients with syphilis and 76
      healthy controls. Sera were also inhibited with cardiolipin micelles and tested
      for aCL and a beta 2 GP-I activities. RESULTS: Twelve patients with primary APS
      but no syphilis patient or control subject had IgG to phospholipid-free beta 2 GP
      I (p < 0.0001) for both comparisons). The aCL activity was inhibited with
      cardiolipin micelles but this treatment had less effect on a beta 2 GP-I
      activity. We found no IgM a beta 2 GP-I in any serum. Nine of 14 patients had had
      lupus anticoagulant activity; 8 of these had a beta 2 GP-I. CONCLUSION: Patients
      with primary APS frequently have IgG a beta 2 GP-I that appear to differ from
      aCL. If aCL present in patients with primary APS actually react with a
      phospholipid induced neoepitope on beta 2 GP-I, as recently proposed, patients
      with primary APS have autoantibodies against 2 epitopes on beta 2 GP-I. Lack of a
      beta 2 GP-I in patients with syphilis might also contribute to protection from
      developing the APS.

PMID- 8991989
TI  - Clinical manifestations of the antiphospholipid syndrome in patients with
      systemic lupus erythematosus associate more strongly with anti-beta 2
      glycoprotein-I than with antiphospholipid antibodies.
AB  - OBJECTIVE: To investigate antibodies to phospholipid-free beta 2-glycoprotein-I
      (a beta 2 GP-I) in the serum of patients with systemic lupus erythematosus (SLE).
      METHODS: We studied alpha beta 2 GP-I by Western blot, dot blot, and ELISA in 94
      patients with SLE. Twenty-one had antiphospholipid syndrome (APS) by clinical and
      serological criteria, 33 had neither of these features, 18 had the clinical
      criteria for APS but no serum antiphospholipid antibodies (aPL). and 22 had
      positive aPL but no related clinical manifestations. As controls, we also studied
      76 normal sera. Sera were also inhibited with cardiolipin micelles and tested for
      anticardiolipin antibodies (aCL) or a beta GP-I activities. RESULTS: Thirty-five
      of 39 patients with SLE with clinical manifestations of APS has serum a beta 2 GP
      I, while only 2 of 55 patients with SLE without such clinical manifestations had
      them (p = 0.000000001). Sixteen patients with SLE with clinical APS but aPL
      negative were a beta GP-I positive. All 35 patients with SLE who were a beta 2 GP
      I positive had vascular manifestations, but these antibodies were present in only
      4 of 55 patients with SLE without vascular manifestations (p = 0.00000001). No
      patient having either aPL or a beta 2 GP-I had clinical manifestations of APS,
      whereas all 19 patients positive for both antibodies had clinical APS. The a beta
      2 GP-I positive, aPL negative patients with SLE had clinical APS more frequently
      (16/18) than did a beta GP-I negative, aPL positive patients with SLE (2/24) (p =
      0.000000001). The association of clinical manifestations of APS with a beta 2 GP
      I was stronger than with aPL. Inhibition studies also indicate that aPL and a
      beta 2 GP-I are 2 different antigen/antibody systems. CONCLUSIONS: Our findings
      indicate that the so called APS associates strongly with antibodies recognizing
      phospholipid-free beta 2 GP-I. There are patients' sera that also recognize
      cardiolipin and/or its cofactor beta 2 GP-I, the latter perhaps by reacting with
      a neoepitope on this protein that appears after its interaction with cardiolipin.
      These would be the previously considered (beta 2 GP-I dependent) aCL.

PMID- 8991990
TI  - Polyamines enhance calcium pyrophosphate dihydrate crystal dissolution.
AB  - OBJECTIVE: Alkaline phosphatase (ALP), an enzyme with pyrophosphatase (PP(i)ase)
      activity, can dissolve calcium pyrophosphate dihydrate (CPPD) crystals. We
      investigated the CPPD crystal dissolution activity of polyamines, substrates
      known to enhance PP(i)ase activity. METHODS: An in vitro model system for crystal
      enzyme interaction was used to assess CPPD crystal dissolution both biochemically
      and morphologically. RESULTS: We demonstrated biochemically and morphologically
      that polyamines such as spermine and spermidine can enhance CPPD crystal
      dissolution activity of ALP. Polyamines enhanced ALP induced CPPD crystal
      dissolution and ALP PP(i)ase activity differentially. By scanning electron
      microscopy, we observed that polyamines enhanced dissolution stereoselectively at
      the small end faces (optical 010 faces) of CPPD crystals, indicated by the
      presence of etch pits. CONCLUSION: Polyamines assist ALP to promote the
      stereoselective dissolution of CPPD crystals. In addition to implications for
      CPPD crystal dissolution, as ALP is present intracellularly, these studies
      suggest that polyamines and ALP have synergistic effects when ALP PP(i)ase
      activity is required for intracellular energy metabolism.

PMID- 8991991
TI  - Early ultrastructural changes of articular cartilage and synovial membrane in
      experimental vitamin A-induced osteoarthritis.
AB  - OBJECTIVE: To evaluate the sequential ultrastructural changes of the articular
      cartilage and synovial membrane in the earliest phases of the vitamin A model of
      osteoarthritis (OA) in the rabbit. METHODS: The superficial layer of the weight
      bearing zone of the articular cartilage and the synovial membrane from
      femorotibial joints of 12 osteoarthritic rabbits were evaluated 3, 6, and 9 days
      after the triggering intraarticular injection of 100,000 i.u. of retinol
      palmitate. Four uninjected rabbits were used as controls. RESULTS: At 3 days,
      ultrastructural changes of chondrocytes could be seen (hypertrophic cells with
      increased lipid droplets, chondrocytes rich in microfilaments and glycogen, and
      some degenerating cells) with no evident lesions of the matrix. The synovium was
      similar to that of the control rabbits. At 6 days, chondrocyte changes seemed
      almost identical to those of 3 days, while the synovial membrane appeared
      markedly involved, substituted by a single layer of A-type cells lying on fibrous
      subsynovial tissue in which lymphocytes, mast cells, and blood vessels could be
      seen. Conspicuous alterations and necrobiosis of the cartilaginous cells
      characterized later stages (9 days). The intercellular matrix was mainly made up
      of amorphous material and bundles of collagen fibers. The synovial membrane was
      transformed into a thick fibrous tissue partially covered with scattered cells no
      longer distinguishable as A or B type. CONCLUSION: Our data suggest that in the
      vitamin A model of OA the initial metabolic changes of the chondrocytes have a
      pivotal role in determining the relentless cascade of events leading to the full
      expression of this disease. Moreover, although several studies have been carried
      out on the early changes in experimental OA, no complete morphological
      evaluations on the developmental aspect of this model have been available.

PMID- 8991992
TI  - Comparison of the nitric oxide synthase inhibitors methylarginine and
      aminoguanidine as prophylactic and therapeutic agents in rat adjuvant arthritis.
AB  - OBJECTIVE: To compare the nitric oxide synthase (NOS) inhibitors NG-methyl-L
      arginine (L-NMA) and aminoguanidine (AG) as prophylactic and therapeutic agents
      in rat adjuvant induced arthritis (AIA). METHODS: Arthritis was induced in male
      Lewis rats by the injection of adjuvant into the base of the tail. L-NMA or AG
      was administered twice daily by gastric intubation starting at the time of
      adjuvant injection, just before the onset of clinical symptoms, or after the
      onset of clinical symptoms. Paw swelling, plasma fibrinogen levels and urinary
      NO2-/NO3- excretion were measured to assess the effect of the inhibitors on the
      arthritis response and whole body NO biosynthesis. Selected joints were also
      evaluated histopathologically. The abilities of L-NMA, AG and another NOS
      inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), to inhibit NO production by
      chondrocytes and synoviocytes were also compared. RESULTS: Treatment with L-NMA
      (400 mg/kg/day) or AG (500 mg/kg/day) reduced the urinary excretion of NO2-/NO3-
      to the control level. L-NMA suppressed the development of AIA when administered
      prophylactically; however, its antiarthritic properties declined with increasing
      delay of application. It was only weakly effective against established AIA. AG
      had neither a prophylactic nor a therapeutic antiarthritic effect. AG and L-NAME
      were much weaker inhibitors of NO production by chondrocytes and synoviocytes
      than L-NMA. CONCLUSION: Although L-NMA completely suppresses the development of
      AIA when administered prophylactically, it is much less effective when
      administered therapeutically. Furthermore, not all inhibitors of NOS show equal
      prophylactic activity against AIA. In addition, NOS inhibitors may be only weakly
      therapeutic, or even detrimental, in established disease. These findings should
      be considered when evaluating NOS inhibitors as potential therapeutic agents for
      the treatment of established human arthritis.

PMID- 8991993
TI  - Quantitative magnetic resonance imaging predicts clinical outcome of core
      decompression for osteonecrosis of the femoral head.
AB  - OBJECTIVE: To determine whether the course of femoral head osteonecrosis after
      core decompression can be predicted from the extent of necrotic bone in the
      preoperative magnetic resonance imaging (MRI). METHODS: In 31 femoral head
      lesions (Ficat stage I or II), the percentage volume of necrotic bone was
      calculated by dividing the sum of the necrotic areas from all MRI slices by the
      sum of the femoral head areas. Osteonecrosis risk factors, pain scores, and the
      need for further surgery were assessed at a minimum of 12 mo post-core
      decompression. Clinical outcomes were considered good when post-core
      decompression pain scores improved and further surgery was not required. RESULTS:
      Fourteen of the 15 hips with good outcomes after a mean followup of 32 mo had
      less than 21% femoral head involvement. All 16 hips with poor outcomes after a
      mean followup of 17 mo had more than 21% of the femoral head affected.
      CONCLUSION: Quantitative MRI of femoral head necrosis was a useful predictor of
      clinical outcome following core decompression.

PMID- 8991994
TI  - An international comparison of the estimated effect of the aging of the
      population on the major cause of disablement, musculoskeletal disorders.
AB  - OBJECTIVE: To illustrate quantitatively the effect of the aging of the population
      on the prevalence of chronic disorders by comparing the projected frequency of
      musculoskeletal (MSK) disorders in 3 comparatively "young" countries, Australia,
      Canada, and the United States, and 3 comparatively "old" countries, France, the
      United Kingdom, and Sweden. METHODS: Age specific rates for MSK disability in
      Canada were applied to World Bank population estimates and projects to estimate
      prevalence rates and numbers of persons with MSK disability in the years 1985,
      2000, 2010, and 2020. RESULTS: The age structure of the populations affected
      baseline rates for MSK disability. Increases in both prevalence and numbers
      affected are expected for all countries between 1985 and 2020, up to a 34%
      increase in prevalence in Canada, and an 88% increase in numbers in Australia.
      CONCLUSION: The aging of the population is likely to result in a disproportionate
      increase in the number of people with chronic disabling disorders, which will be
      taking place against a background of a decreasing or static number of young
      adults, with implications for meeting needs for health care and community
      support.

PMID- 8991995
TI  - Effects of antiinflammatory drugs on the progression of osteoarthritis of the
      knee. LINK Study Group. Longitudinal Investigation of Nonsteroidal
      Antiinflammatory Drugs in Knee Osteoarthritis.
AB  - OBJECTIVE: To compare the rate of radiographic progression in knee osteoarthritis
      (OA) comparing indomethacin with placebo and tiaprofenic acid with placebo.
      METHODS: Rate of radiographic progression of OA of the knees was studied in 812
      patients randomized double blind parallel group study at 20 rheumatology clinics
      in the United Kingdom and analyzed sequentially. Patients received either
      indomethacin 25 mg three times daily, tiaprofenic acid 300 mg twice daily, or
      matched placebo. All had access to paracetamol as a rescue analgesic. Joint space
      narrowing was measured by a 6 point grading scale, using radiographs taken with a
      standardized technique at recruitment and annually thereafter. RESULTS: Three
      hundred and seventy six patients completed at least one year of study medication
      and therefore contributed evaluable results. More than twice as many patients
      showed deterioration in the indomethacin group as in the placebo group; of 170
      available patients at the 3rd interim analysis, 40 of 85 receiving indomethacin
      had deteriorated compared to 19 of 85 receiving placebo, a statistically
      significant difference (p = 0.009). No statistically significant difference (p =
      0.308) was found between tiaprofenic acid and placebo at the 7th interim
      analysis, the conclusion of the study. CONCLUSION: Indomethacin increased the
      rate of radiological deterioration of joint space in patients with OA of the
      knee; tiaprofenic acid did not.

PMID- 8991996
TI  - Fast food arthritis--a clinico-pathologic study of post-Salmonella reactive
      arthritis.
AB  - OBJECTIVE: To study the clinical presentation, immunogenetics, and serum immune
      response to lipopolysaccharide (LPS) in a cohort of patients with post-Salmonella
      reactive arthritis (ReA). METHODS: A validate ReA screening questionnaire (Quest
      2) was mailed to 919 individuals reporting symptoms of gastroenteritis to the
      health department after eating at a single restaurant. Three hundred twenty-one
      persons returned questionnaires; 170 reported symptoms outside the
      gastrointestinal tract; 23 of those 170 reporting persistent joint symptoms were
      seen 4 to 16 weeks after the outbreak and 5 of the 23 were seen in followup 12 to
      20 weeks later. Clinical features, HLA Class I typing, serum soluble CD8 levels,
      and serum antibodies to gram negative LPS by ELISA were determined. RESULTS:
      Joint complaints were reported more frequently by individuals with a longer
      duration of diarrhea. Upper extremity joints were frequently involved, and 66%
      reported one or more extraarticular symptoms of Reiter's syndrome. Three of 5
      typed individuals were HLA-B27 positive, including 3 of the 4 most severely
      involved. Serum soluble CD8 levels correlated poorly with disease activity
      measured either clinically or by C-reactive protein. Antibodies to Klebsiella and
      Shigella LPS rose over time, while antibodies to Salmonella LPS fell. CONCLUSION:
      The clinical picture of post-Salmonella ReA is less stereotyped than often
      assumed, although severity correlated with HLA-B27 status. The association of
      joint symptoms with duration of diarrhea and the kinetics of the anti-LPS
      antibody response support the hypothesis that abnormal gut permeability plays a
      role in the pathogenesis of post-Salmonella ReA.

PMID- 8991997
TI  - Bicipital synovial cysts in juvenile rheumatoid arthritis: clinical description
      and sonographic correlation.
AB  - OBJECTIVE: To describe the presentation and clinical course of bicipital synovial
      cysts in 6 patients with juvenile rheumatoid arthritis (JRA) and to elucidate
      their anatomy using ultrasonography. METHODS: A clinical description of the cyst,
      JRA subtype, activity of concurrent arthritis, systemic disease features, and
      erythrocyte sedimentation rate was recorded for each patient. Ultrasonographic
      examination of the cyst was performed for each patient. RESULTS: Bicipital cysts
      generally presented as a sudden painless swelling on the flexor aspect of the
      upper arm, but on was in the forearm. Five of 6 patients had systemic disease.
      All patients had active arthritis when the cysts developed. Five of 6 cysts
      resolved spontaneously in less than 12 weeks. Ultrasonography confirmed a cystic
      structure in all patients, and in all cases was associated with thickening of the
      biceps tendon. Fluid was found within or adjacent to the biceps tendon in all
      cases. CONCLUSION: Bicipital synovial cysts should be considered a cause of acute
      arm swelling in patients with JRA, especially those with systemic disease.
      Ultrasonography is a useful diagnostic adjunct in this condition. This condition
      is generally self-resolving.

PMID- 8991998
TI  - Temporomandibular joint and mandibular growth alterations in patients with
      juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To determine the frequency and type of lesions of the
      temporomandibular joints (TMJ) as well as orthodontic alterations present in
      patients with juvenile rheumatoid arthritis (JRA). METHODS: Twenty-six patients
      had their TMJ evaluated clinically and by high resolution computer tomography.
      The patients were also submitted to orthodontic evaluation. Children with
      isolated malocclusion were used as a control group. RESULTS: Computer tomography
      detected TMJ alterations in 13 (50%) patients with JRA. Bilateral mild lesions
      were the most frequent. TMJ alterations were especially observed in young
      patients with JRA with the systemic and polyarticular type of onset. Worse
      functional class and corticosteroid therapy were also related to TMJ involvement.
      We observed orthodontic alterations in 18 patients with JRA (69%): midline
      deviation, convex facial profile. Class II molar relation, crowded lower anterior
      teeth, anterior open bite, and reduction in the maximum opening of the mouth.
      Severe TMJ lesions were correlated to cephalometric alterations, suggesting
      decreased mandibular growth.

PMID- 8991999
TI  - Reiter's syndrome associated with cryptosporidial gastroenteritis.
AB  - We describe a child with Reiter's syndrome (RS) associated with cryptosporidial
      gastroenteritis. Two children have recently been reported with reactive arthritis
      due to Cryptosporidium: however, our child represents the first pediatric case of
      RS secondary to cryptosporidiosis.

PMID- 8992000
TI  - Onset of rheumatoid arthritis after surgical treatment of Cushing's disease.
AB  - We describe a patient with Cushing's disease who, shortly after trans-sphenoidal
      surgical resection of an adrenocorticotropic hormone secreting pituitary
      microadenoma and specifically at the time of normalization of her serum cortisol
      level, developed a subacute episode of symmetric polyarticular synovitis. This
      episode lasted for one month; however, it did not resolve completely and
      progressed after 3.5 years of diffuse arthralgias and morning stiffness to
      seropositive and erosive rheumatoid arthritis (RA). Review of the literature
      revealed 3 additional patients with RA with a similar course. These patients may
      represent a natural illustration of the antiinflammatory effects of
      supraphysiological levels of endogenous glucocorticoids.

PMID- 8992001
TI  - Response to methotrexate in a patient with idiopathic eosinophilic fasciitis,
      morphea, IgM hypergammaglobulinemia, and renal involvement.
AB  - A 35-year-old man with idiopathic eosinophilic fasciitis (EF) and morphea
      developed renal disease characterized by microscopic hematuria, nephrotic range
      proteinuria, and rapidly progressing hypertension, an association that has not
      previously been reported in EF. Initial clinical symptoms of EF began in July
      1989; peripheral eosinophilia peaked at 30% in August 1990; an abnormal
      urinalysis was first observed in March 1992 and subsequently a renal biopsy was
      performed. Renal biopsy demonstrated focal segmental glomerulosclerosis and a
      subepithelial immune-type deposit. Partial fasciectomy and a course of
      methotrexate resulted in overall functional improvement of his extremities.
      Proteinuria and hematuria was reduced during methotrexate therapy.

PMID- 8992002
TI  - Bursitis of the iliopsoas: four cases with pain as the only clinical indicator.
AB  - Bursitis of the iliopsoas is a clinical entity rarely encountered, and may be
      underdiagnosed. Reports in the literature have usually considered the condition
      to result from an increase in bursal volume. Bursitis of the iliopsoas is most
      commonly observed in conjunction with pathologies such as rheumatoid arthritis or
      osteoarthritis of the hip, and is rarely reported as an isolated condition. We
      describe 4 cases of bursitis of the iliopsoas in which bursal swelling was absent
      and hip pain was the only clinical indicator. Diagnostic and therapeutic criteria
      based on clinical and radiological criteria are suggested.

PMID- 8992003
TI  - How to apply Larsen score in evaluating radiographs of rheumatoid arthritis in
      long-term studies.
AB  - Radiographs of rheumatoid arthritis in longterm multicenter trials vary in
      quality and precision, making the uniform evaluation of soft tissue swelling,
      osteoporosis and the size of erosions difficult. A modification of Larsen Score
      is presented in which only major differences in osseous and joint space changes
      are determined.

PMID- 8992004
TI  - A modified version of Larsen's scoring method to assess radiologic changes in
      rheumatoid arthritis.
AB  - We describe the development and application of a modified version of the
      radiologic scoring method proposed by Larsen in patients with rheumatoid
      arthritis (RA). We modified Larsen's method adding a semiquantitative description
      of the loss of joint surface area and provide standardized reference films for
      all stages at different anatomical sites (metacarpophalangeal joints, proximal
      interphalangeal joints, wrists, metatarsophalangeal joints). To evaluate the
      method, standard anteroposterior radiographs of hands, wrists and forefeet of 24
      patients with early erosive RA taken at baseline (t0) and after 36 months (t1)
      were read by 2 raters in a blinded fashion. The interrater difference was
      compared with the interpatient (t0 to t1) difference using a hierarchical
      analysis of variance. Moreover, the method was applied to patients included in a
      2 year clinical trial to evaluate the efficacy of intramuscular methotrexate
      (MTX) and gold sodium thiomalate (GSTM) with radiographs taken at baseline and
      after 6, 12, and 24 months. There was a good agreement between the 2 raters and
      the change could be well documented. The estimation of the intrapatient variance
      (at t0 and t1) was 8 times higher than the estimation of the interreader
      variance. The method was easily applicable in 57 patients treated with MTX and 53
      patients under treatment with GSTM, showing a slowing of radiologic progression
      after Month 6 with both drugs. The modification of Larsen's scoring method is a
      reliable measure to assess baseline status and radiologic progression in patients
      with RA.

PMID- 8992005
TI  - Quantitative analysis of hand radiographs in rheumatoid arthritis: time course of
      radiographic changes, relation to joint examination measures, and comparison of
      different scoring methods.
AB  - Quantitative studies of hand radiographs in patients with rheumatoid arthritis
      (RA) indicate that radiographic joint space narrowing and erosion are seen in
      more than 67% of patients within the 1st 2 years of disease, and progresses most
      rapidly during the 1st 5 years of disease, according to currently used scoring
      methods. Radiographic malalignment is rarely seen until after 5 years of disease.
      In cross sectional studies, correlations of radiographic scores with physical
      examination scores are minimally significant for joint tenderness, modestly
      significant for joint swelling, and highly significant for joint deformity and
      limited motion. In cross sectional studies, 3 quantitative methods, the
      Steinbrocker radiographic stage, modified Sharp method, and Larsen method, are
      highly significantly correlated and yield similar results in comparisons with
      other clinical measures.

PMID- 8992006
TI  - Problems in evaluating radiographic findings in rheumatoid arthritis using
      different methods of radiographic scoring: examples of difficult cases and a
      study design to develop an improved scoring method.
AB  - Radiographic scoring is generally accepted as the "gold standard" to follow the
      course of rheumatoid arthritis (RA). Several methods have been developed to
      quantify radiographic changes due to RA. The most widely used methods have been
      proposed by Larsen and Sharp. Problems of the interpretation of the radiograph
      and the design of the scoring methods are not resolved. The design of established
      scoring methods lacks correct correlation to the amount of change on radiographs,
      leading to confounding of the results of the radiographic analysis. Concerns
      arise about the correct interpretation of findings on plain radiographs that are
      caused by having a 2-dimensional picture of a 3 dimensional object. There is no
      agreement which of the different changes caused by RA on the radiograph have to
      be considered and which can be neglected. Examples for these problems are given.
      We compared the established scoring methods of Larsen and Sharp on the same set
      of radiographs with longterm followup using the correct data analysis to provide
      the information needed to design an improved scoring method. Details of the study
      design are reported.

PMID- 8992007
TI  - How to evaluate measuring methods in the case of non-defined external validity.
AB  - In the clinical routine of chronic diseases, a new measurement has to be compared
      to an established criterion to see whether there is agreement on assessing
      disease progress. Because of the nonexistence of established criteria for
      rheumatoid arthritis the evaluation of grading systems for radiological
      assessment needs an alternative approach. Using the measurement error as a
      measure for repeatability and rater agreement in comparison to the progress of
      the grading score might be a solution to this dilemma.

PMID- 8992008
TI  - Future opportunities using technical advantages in picture processing and data
      transfer.
AB  - In recent years there have been many significant developments in the ability to
      process radiographic pictures and transfer the images from one location to
      another, and we can now examine the application of computers in the radiographic
      evaluation of rheumatoid arthritis. Image management and communication systems
      can assist in providing better health care while lowering costs. Although this
      work is still in its infancy, the rapid growth in both hardware capability and
      software techniques will soon make these techniques available to physicians
      everywhere. The expanding capability in the commercial world is being embraced by
      the radiology department, and will soon allow rheumatologists to access images at
      greater distances, and do more with the images which become available.

PMID- 8992009
TI  - Elevated plasma stromelysin levels in arthritis.

PMID- 8992010
TI  - Osteoarthritis and overweight.

PMID- 8992011
TI  - Presence of IgG antiphospholipid autoantibody in nude mice.

PMID- 8992012
TI  - Intraarticular apatite crystal deposition as a predictor of erosive
      osteoarthritis of the fingers.

PMID- 8992013
TI  - Anticardiolipin antibody associated with renal carcinoma.

PMID- 8992014
TI  - Lower extremity hypertrophic osteoarthropathy associated with aortic graft
      infection.

PMID- 8992015
TI  - beta 2-Glycoprotein-I is a cofactor for antibodies reacting with 5 anionic
      phospholipids.

PMID- 8992016
TI  - Achilles and suprapatellar tendinitis due to isotretinoin.

PMID- 8992017
TI  - Arthritis and iritis after bacillus Calmette-Guerin therapy.

PMID- 8992018
TI  - Germany needs national council for cancer research.

PMID- 8992019
TI  - Fluoroquinolones in animal health.
AB  - The fluoroquinolones are a series of synthetic antibacterial agents that are
      undergoing extensive investigation for both human and veterinary use in the
      treatment of a variety of bacterial infections. These agents work through the
      inhibition of DNA gyrase, interfering with the supercoiling of bacterial
      chromosomal material. As a result, these agents are rapidly bactericidal
      primarily against gram-negative bacteria, mycoplasma, and some gram-positive
      bacteria, with most having little to no activity against group D streptococci and
      obligate anaerobic bacteria. Resistance develops slowly and is almost always
      chromosomal and not plasmid-mediated. However, development of resistance to the
      fluoroquinolones and transfer of that resistance among animal and human pathogens
      have become a hotly debated issue among microbiologists. The fluoroquinolones are
      a current antimicrobial class whose use in veterinary medicine is being
      scrutinized. From a pharmacokinetic perspective, these agents are variably but
      well absorbed from the gastrointestinal tract and almost completely absorbed from
      parenteral injection sites, and they are well distributed to various tissues in
      the body. The fluoroquinolones are metabolized and renally excreted, with many of
      them having approximately equal excretion by the hepatic and the renal excretory
      systems. The primary toxicity observed at therapeutic doses involves the
      gastrointestinal system and phototoxicity, although at higher doses central
      nervous system toxicity and ocular cataracts are observed. Administration to
      immature animals may result in erosive arthropathies at weight-bearing joints,
      and administration of high doses to pregnant animals results in maternotoxicity
      and occasionally embryonic death. The fluoroquinolones are approved for
      indications such as urinary tract infections and soft tissue infections in dogs
      and cats and colibacillosis in poultry. Approval for bovine respiratory disease
      in the United States is being sought. Other indications for which the
      fluoroquinolones have been used in animal health include deep-seated infections,
      prostatitis, and other bacterial infections resistant to standard antimicrobial
      therapy.

PMID- 8992020
TI  - Influence of closure of the reticular groove on the bioavailability and
      disposition kinetics of meclofenamate in sheep.
AB  - Sodium meclofenamate is a non-steroidal anti-inflammatory drug with anaphylactic
      protective activity in cattle. The objectives of this study were to describe the
      pharmacokinetic behaviour of sodium meclofenamate after intravenous and oral
      administration to sheep and to determine the influence of closure of the
      reticular groove on the bioavailability of the drug. Sodium meclofenamate was
      administered by the intravenous (2.2 mg/kg) and oral (20 mg/kg) routes to sheep
      (n = 6). During the oral study the reticular groove was closed by intravenous
      administration of lysine vasopressin (0.3 IU/kg) or left open (saline solution).
      The closure of the reticular groove was assessed by determination of the blood
      glucose curves after oral administration of a glucose solution. After intravenous
      administration of meclofenamate, the distribution and elimination half-lives of
      the drug were 7.2 min and 542 min respectively, Vss was 1.68 L/kg and ClB was
      2.47 mliter/min kg. Two different patterns of the plasma concentration curves
      were observed after oral administration of sodium meclofenamate. When the
      reticular groove was closed, two peaks were observed (tmax-1 12-15 min, Cmax-1
      3.30-24.01 micrograms/mliter; and tmax-2' 52.50-75 min, Cmax-2, 6.45-11.08
      micrograms/mliter).

PMID- 8992021
TI  - Amitraz depresses cardiovascular responses to bilateral carotid occlusion.
AB  - The ectoparasiticide amitraz stimulates alpha 2-adrenoceptors to produce side
      effects such as bradycardia and hypotension. The actions of amitraz on
      baroreceptor reflex responses were evaluated in mongrel dogs by occlusion of both
      carotid arteries for 30-s periods. Incremental doses of amitraz given
      intravenously showed that doses of 60 micrograms/kg and above significantly
      depressed pressor responses to carotid occlusion. By comparison, 2 micrograms/kg
      amitraz given by intracisterna magna (i.c.m.) injection significantly depressed
      both blood pressure and heart rate responses. Pretreatment of dogs with i.c.m.
      yohimbine (30 micrograms/kg) prevented the depressant effects of amitraz on the
      reflex, but prazosin (20 micrograms/kg), in separate experiments, had no effect.

PMID- 8992022
TI  - Pharmacokinetics of oxcarbazepine in the dog.
AB  - Oxcarbazepine has been proven to be a promising new antiepileptic drug for the
      treatment of human epilepsy. Unlike carbamazepine, it is not oxidatively
      metabolized in humans, and therefore causes almost no induction of hepatic
      enzymes at clinically effective dosages. Though showing similar efficacy to
      carbamazepine, it has been reported to cause significantly fewer side-effects. It
      was the purpose of the present study to determine whether oxcarbazepine might be
      suitable for the treatment of canine epilepsy. In single-dose experiments, 40
      mg/kg oxcarbazepine as a suspension was administered to seven dogs via gastric
      tube. Plasma concentrations reached peak concentrations of 2.4-8.8
      micrograms/mliter at about 1.5 h and declined with an elimination half-life of
      approximately 4 h. The corresponding concentrations of its metabolite, 10,11
      dihydro-10-hydroxycarbamazepine, did not exceed 1 micrograms/mliter. During
      continued treatment for 8 days, doses of 30 and 50 mg/kg were administered orally
      in capsules to two dogs three times a day. Plasma concentrations showed a
      pronounced decline from day 3, and the terminal half-life decreased to 2 h and 1
      h. This is considered to be the result of oxcarbazepine inducing its own
      metabolism. The data reveal that oxcarbazepine, compared with former results with
      carbamazepine, offers no advantage for the treatment of epileptic dogs.

PMID- 8992023
TI  - Effects of age on the pharmacokinetics of single dose ceftiofur sodium
      administered intramuscularly or intravenously to cattle.
AB  - The effects of maturation on the intravenous (IV) and intramuscular (IM)
      pharmacokinetics of ceftiofur sodium following a dose of 2.2 mg ceftiofur
      equivalents/kg body weight were evaluated in 16 one-day-old Holstein bull calves
      (33-53 kg body weight initially; Group 1) and 14 six-month-old Holstein steers
      (217-276 kg body weight initially; Group 2). Group 1 calves were fed unmedicated
      milk replacer until 30 days of age and were then converted to the same
      roughag/concentrate diet as Group 2. Groups 1-IV and 2-IV received ceftiofur
      sodium IV, and Groups 1-IM and 2-IM received ceftiofur sodium IM. Group 1 calves
      were dosed at 7 days of age and at 1 and 3 months of age; group 2 calves were
      dosed at 6 and 9 months of age. Blood samples were obtained serially from each
      calf, and plasma samples were analysed using an HPLC assay that converts
      ceftiofur and all desfuroylceftiofur metabolites to desfuroylceftiofur acetamide.
      Cmax values were similar in all calves, and were no higher in younger calves than
      in older calves. Plasma concentrations remained above 0.150 microgram ceftiofur
      free acid equivalents/mliter for 72 h in 7-day-old calves, but were less than
      0.150 microgram/mliter within 48 h following IV or IM injection for 6- and 9
      month-old calves. Intramuscular bioavailability, assessed by comparing the model
      derived area under the curve (AUCmod) from IM and IV injection at each age,
      appeared to be complete. After IV administration, the AUCmod in 7-day-old and 1
      month-old calves (126.92 +/- 21.1 micrograms.h/mliter and 135.0 +/- 21.6
      micrograms.h/mliter, respectively) was significantly larger than in 3-, 6- and 9
      month-old calves (74.0 +/- 10.7 micrograms.h/mliter, 61.0 +/- 17.7
      micrograms.h/mliter and 68.5 +/- 12.8 micrograms.h/mliter, respectively; P <
      0.0001). The Vd(ss) decreased linearly within the first 3 months of life in
      cattle (0.345 +/- 0.0616 L/kg, 0.335 +/- 0.919 L/kg and 0.284 +/- 0.0490 L/kg,
      respectively; P = 0.031), indicative of the decreasing extracellular fluid volume
      in maturing cattle. The ClB was significantly smaller in 7-day-old and 1-month
      old calves (0.0178 +/- 0.00325 L/h.kg and 0.0167 +/- 0.00310 L/h.kg,
      respectively) than in 3-, 6- and 9-month-old calves (0.0303 +/- 0.0046 L/h.kg,
      0.0398 +/- 0.0149 L/h.kg and 0.0330 +/- 0.00552 L/h.kg, respectively; P < or =
      0.001). This observation may be indicative of maturation of the metabolism and/or
      excretion processes for ceftiofur and desfuroylceftiofur metabolites. The
      approved dosage regimens for ceftiofur sodium of 1.1-2.2 mg/kg administered once
      daily for up to 5 consecutive days will provide plasma concentrations above the
      MIC for bovine respiratory disease pathogens for a longer period of time in
      neonatal calves than in older calves. Peak plasma concentrations of ceftiofur and
      desfuroylceftiofur metabolites were no higher in neonatal calves than in more
      mature cattle, highly suggestive that peak tissue concentrations would be no
      higher in neonatal calves than in more mature cattle.

PMID- 8992024
TI  - Pharmacokinetics of cefoperazone in horses.
AB  - The pharmacokinetics and bioavailability of cefoperazone (CPZ) were studied
      following intravenous (IV) and intramuscular (IM) administration of single doses
      (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples
      were measured following IV administration. CPZ concentrations in serum, synovial
      fluid and spongy bone samples were measured following IM administration. After IV
      administration a rapid distribution phase (t1/2 (alpha): 4.22 +/- 2.73 min) was
      followed by a slower elimination phase (t1/2(beta) 0.77 +/- 0.19 h). The apparent
      volume of distribution was 0.68 +/- 0.10 L/kg. Mean synovial fluid peak
      concentration was 5.76 +/- 0.74 microgram/mliter. After IM administration a
      bioavailability of 42.00 +/- 5.33% was obtained. Half-life of absorption was 2.51
      +/- 0.72 min and t1/2(beta) was 1.52 +/- 0.15 h. The mean synovial fluid and
      spongy bone peak concentrations at 2 h after IM administration were 2.91 +/- 0.85
      microgram/mliter and 5.56 +/- 0.70 microgram/mliter, respectively.

PMID- 8992025
TI  - Characterization of a sterile soft-tissue inflammation model in thoroughbred
      horses.
AB  - This paper describes the use of subcutaneously-placed tissue chambers as a
      sterile soft-tissue inflammation model in Thoroughbred horses. Acute, non-immune
      inflammation was initiated by injecting a sterile lambda carrageenan solution
      into a tissue chamber. This model was used to study the temporal changes in
      oxygen and carbon dioxide tensions, pH, bicarbonate, protein, albumin,
      prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) concentrations, cell counts and
      differential counts in tissue fluid from inflamed tissue chambers and control
      chambers. Skin temperatures over control and inflamed chambers were also
      compared. Carrageenan-induced inflammation resulted in significant increases in
      tissue-fluid carbon dioxide tension, leucocyte count, albumin, and PGE2 and LTB4
      concentrations. It also resulted in a significant decrease in tissue fluid pH and
      HCO3-concentration. Inflammation did not result in significant changes in tissue
      fluid protein concentration, differential cell counts or skin temperature over
      the chambers. The use of this type of tissue chamber is well-suited for studying
      the pathophysiology of a self-contained, non-immune inflammatory process. The
      model described in this paper could prove to be very useful in studies of the
      distribution of anti-inflammatory drugs and the effects of such drugs on various
      aspects of the inflammatory process.

PMID- 8992026
TI  - Comparison of the pharmacokinetics and local tolerance of three injectable
      oxytetracycline formulations in pigs.
AB  - The pharmacokinetic properties and local tolerance of three oxytetracycline
      formulations, one conventional (Engemycine, 10%) and two long-acting (Oxyter LA,
      20% and Terramycin LA, 20%) were compared in clinically healthy cross-bred pigs
      following intramuscular injection of single doses (20 mg/kg body weight) in the
      neck region. Non-compartmental methods were used to calculate the pharmacokinetic
      parameters. Assessment of local tolerance was based on serum creatine
      phosphokinase (CPK) concentration and a combination of echographical, macroscopic
      and histological examinations of the intramuscular injection site. Statistically
      significant differences (one-way analysis of variance, F-test) were obtained
      between the three formulations in peak plasma concentration, peak time and mean
      residence time. Area under the curve did not differ significantly between the
      formulations. Using the Students t-test for paired data, the two long-acting
      formulations differed significantly in peak plasma concentration and peak time.
      Both of the long-acting formulations differed significantly from the conventional
      formulation in the peak time and mean residence time. All three formulations
      produced an increase in serum CPK concentrations. The increase in CPK
      concentration was present from 6 to 24 h post treatment for Terramycin LA, from 6
      to 72 h for Oxyter LA and from 6 to 96 h for Engemycine (the conventional
      formulation). Echographical examination of the injection site showed lesions of
      an inflammatory type up to 96 h after IM injection of the drug products, whereas
      from 7 days the lesions represented primarily scar formation. Histological
      examination of tissue from the injection site did not correlate with
      echographical scores. The results obtained in this study show that the long
      acting formulations provide significantly longer mean residence times of
      oxytetracycline than the conventional formulation, and that local tolerance at
      the IM injection site was similar for all three formulations under the
      experimental conditions used in this study. It can be concluded that the long
      acting formulations provide the advantage of a longer dosage interval when
      administered to pigs by intramuscular injection in the neck region at a dose of
      20 mg/kg body weight.

PMID- 8992027
TI  - Pharmacokinetics of marbofloxacin in dogs after oral and parenteral
      administration.
AB  - Six dogs were treated with a single intravenous (i.v.) dose (2 mg/kg) of
      marbofloxacin, followed by single oral (p.o.) doses of marbofloxacin at 1, 2 and
      4 mg/kg, according to a three-way crossover design. The same experimental design
      was used for the subcutaneous (s.c.) route. In addition, a long-term trial
      involving eight dogs given oral doses of marbofloxacin at 2, 4 and 6 mg/kg/day
      for thirteen weeks was carried out. Plasma and urine samples were collected
      during the first two trials, plasma and skin samples were collected after the
      second of these trials. Plasma, urine and skin concentrations of marbofloxacin
      were determined by a reverse phase liquid chromatographic method. Mean
      pharmacokinetic parameters after i.v. administration were the following: t1/2
      beta = 12.4 h; ClB = 0.10 L/h.kg; Varea = 1.9 L/kg. The oral bioavailability of
      marbofloxacin was close to 100% for the three doses. At 2 mg/kg, Cmax of 1.4
      micrograms/mliter was reached at tmax of 2.5 h. Mean AUC and Cmax values had a
      statistically significant linear relationship with the doses administered. About
      40% of the administered dose was excreted in urine as unchanged parent drug.
      After s.c. administration, the calculated parameters were close to those obtained
      after oral administration, except tmax (about 1 h) which was shorter. The mean
      skin to plasma concentration ratio after the long-term trial was 1.6, suggesting
      good tissue penetration of marbofloxacin.

PMID- 8992028
TI  - Pharmacokinetics and anti-trichomonal efficacy of a dimetridazole tablet and
      water-soluble powder in homing pigeons (Columba livia).
AB  - The anti-trichomonal efficacy and pharmacokinetics of dimetridazole were
      investigated in the homing pigeon (Columba livia). Dimetridazole was formulated
      for drinking water medication and as a prolonged-release tablet. To suppress a
      Trichomonas gallinae infection successfully, medicated drinking water containing
      dimetridazole (400 mg/L) had to be administered for at least 3 days. A two-day
      treatment with a dimetridazole tablet (20 mg/tablet) in fasted, as well as in
      fed, pigeons was shown to be ineffective. After intravenous administration of 20
      mg dimetridazole, the drug plasma concentration-time profile fitted a one
      compartment open model with a mean half-life of 3.9 h. The absolute
      bioavailability of the tablet in fasted pigeons was 83.8%. The bioavailability of
      the tablet administered with food was reduced by 20%. Dimetridazole was rapidly
      metabolised to (1-methyl-5-nitroimidazol-2-yl) methanol.

PMID- 8992029
TI  - The pharmacokinetics of dexamethasone in the thoroughbred racehorse.

PMID- 8992030
TI  - Pharmacokinetics of indomethacin in cattle.

PMID- 8992031
TI  - The pharmacokinetics of a long-acting formulation of oxytetracycline in sheep and
      goats.

PMID- 8992032
TI  - Surveillance of drug prescribing for farmed fish in Norway: possible applications
      of computerized prescription information.

PMID- 8992033
TI  - Chirality: a major issue in veterinary pharmacology.

PMID- 8992034
TI  - [A study of surgical treatment in lung cancer over 75 years of age-effect of
      epidural anesthesia for protection of postoperative coughing disturbance].
AB  - 29 patients over 75 years of age in 221 patients undergoing resection of lung
      cancer from January of 1990 through December of 1994 were studied for the
      occurrence of expectoration disturbance (atelectasis), the effect of epidural
      anesthesia for protection of it. Atelectasis was observed in 8 (27.6%) of 29. In
      a group received epidural anesthesia (EA) during the early postoperative phase, 1
      of 5 patients developed atelectasis. In 192 patients below 75 years of age,
      atelectasis was observed in 40 (20.8%) of them, so in a group received epidural
      anesthesia (EA) during the early postoperative phase, only 2 of 42 patients
      (4.8%) developed atelectasis. This value was significantly lower than that value
      (25.3%) in a group without EA. In conclusion, in the group below 75 years of age,
      EA during the early postoperative phase may be useful in inhibiting the
      occurrence of atelectasis, an important one of the postoperative lung
      complications.

PMID- 8992035
TI  - [Antiplatelet therapy after open heart surgery].
AB  - This study evaluated the effects of an antiplatelet drug for the patients after
      open heart surgery. Dipyridamole (D), aspirin (A), ticlopidine (T) and
      sarpogrelate hydrochloride (S) were chosen as an antiplatelet drug. The 6 groups
      were devided into as G 1 with warfarin (W) and D, as G 2 with W alone, as G 3
      with A and D, as G 4 with A alone, as G 5 with A and T, and as G 6 with A and S.
      The indices of anticoagulation and antiplatelet were as follows: TT, APTT, PT, D.
      Dimer, fibrinogen, TXB2, 6 kPGF1 alpha, beta TG, vWF and platelet aggregation
      with Grading Curve methods. The results showed that D.Dimer was beyond the normal
      range in G 1 and G 2. Thromboxane B 2 was increased markedly in G 1 and G 2 and
      showed under the normal range in G 3 and G 6. In all groups, 6 kPGF1 alpha showed
      low levels than normal. Activation of platelet causes the increased beta TG which
      was not suppressed with the antiplatelet drugs administered. The platelet
      aggregation was not suppressed in G 1 and G 2. Mild to moderate suppression was
      seen in G 3 and G 4 with no difference between the two group. Moderate to marked
      suppression was demonstrated in G 5 and G 6. This study demonstrated that
      dipyridamole had no effects as antiplatelet function. Aspirin showed antiplatelet
      effects and the combination of aspirin with the another antiplatelet drugs
      demonstrated the additional effects.

PMID- 8992036
TI  - [Experience of carperitide (synthetic human-atrial natriuretic peptide) after
      cardiovascular surgery].
AB  - Recently carperitide (synthetic human-atrial natriuretic peptide) in known to be
      useful for the care of acute heart failure. Stretch of the atrial wall has been
      suggested to be on one of the important factors involved in peptide release. The
      8 patients were undertaken cardiac surgery. Carperitide was infused intravenously
      during postoperative period in these patients and the effects of carperitide were
      examined. Blood pressure (BP), central venous pressure (CVP), mean pulmonary
      arterial pressure (PA), pulmonary capillary wedge pressure (PCWP), cardiac index
      (CI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR)
      were monitored by Swan-Ganz catheter, and urinary volume per body weight (UV/kg)
      were measured. The variables were determined before and after the intravenous
      infusion of carperitide at 0.1 to 0.2 microgram/kg/min. BP, CVP, PA, PCWP, SVR,
      and PVR were decreased, and CI and UV/kg were increased after administration of
      carperitide. These results suggest that carperitide is the useful agent for the
      postoperative care of cardiovascular surgery especially in the point of
      decreasing BP and increasing urination.

PMID- 8992037
TI  - [Rib cross thoracotomy for a huge thoracic lesion].
AB  - Panpleuropneumonectomy, resection of a huge tumor in the thorax or operation of
      thoracic aneurysm requires good view of the entire thorax. Two separate incisions
      of lateral thoracotomy would not usually provide a sufficient operative field.
      The procedure of rib cross thoracotomy is as follows: The 6th, 7th, 8th, 9th rib
      with the intercostal muscle and vessels are cut at mid axillary line and removed
      1 cm length at each edge of the ribs. The posterior half of the 6th ribs is
      removed. Thorax is entered posterioly at the 5th intercostal space and caudally
      to the 9th rib at the axillary line and anteriorly at the same intercostal space.
      Two rib expanders are needed.

PMID- 8992039
TI  - [Obstruction of the true lumen by retrograde perfusion during repair of DeBakey
      type I aortic dissection: a case report].
AB  - Retrograde femoral perfusion is often used during the repair of DeBakey type I
      aortic dissections, however, it may cause serious ischemic damage of vital organs
      even though the arterial cannula is properly placed. A 58-year-old woman with
      chest pain was admitted to our hospital. She was operated on urgently because
      chest computed tomograms revealed that she suffered from a DeBakey type I aortic
      dissection. A ringed graft, 22 mm in diameter, was implanted into the ascending
      aorta using retrograde perfusion through the right femoral artery. Following the
      removal of the aortic cross-clamp and rewarming, the prosthetic graft remained
      flaccid and the heart failed to resume beating. We speculated that retrograde
      femoral perfusion caused the true lumen obstruction while distending the false
      lumen. This resulted in blocking reperfusion of the coronary arteries. After
      antegrade perfusion was initiated through an 8 mm Dacron graft which was
      anastmosed to the ringed graft, the heart soon resumed beating. During the repair
      of DeBakey type I aortic dissections, this serious complication should be
      anticipated. If it occurs, retrograde femoral perfusion must be exchanged for
      antegrade aortic perfusion before irreversible changes occur.

PMID- 8992038
TI  - [A case report on graft replacement of ruptured aneurysm of the arch and the
      descending thoracic aorta associated with dense pulmonary adhesion].
AB  - A 73-year-old patient had been followed for aortic arch aneurysm of 54 mm in
      diameter. He was hospitalized complaining of chest and back pain. A chest CT scan
      showed ruptured aortic arch aneurysm extending to mid-descending thoracic aorta,
      and an emergent operation was decided. The trachea was intubated with a univent
      tube providing a movable blocker (System Corporation) which was directed to the
      left bronchus for differential lung ventilation. The descending thoracic aorta
      was exposed through the left 4th intercostal thoracotomy just at the site
      intending to anastomose a prosthetic graft because of dense pulmonary adhesion.
      The ascending and arch aorta was approached via median sternotomy. Under deep
      hypothermia and retrograde cerebral perfusion, total arch and descending aortic
      replacement was performed using an arch graft providing four branch grafts for
      neck vessels reconstruction and pump perfusion. The patient showed moderate
      pulmonary bleeding during and after cardiopulmonary bypass, but improved
      gradually. He was weaned from the respirator on the 13th post-operative day.
      During extensive thoracic aortic surgery using left thoracotomy combined with
      median sternotomy, left lung deflation using a univent tracheal tube with a
      blocker, and circulatory arrest during distal aortic anastomosis, are useful in
      preventing lethal pulmonary bleeding caused by lung injury under the fully
      heparinized condition. However, in cases associated with dense pulmonary
      adhesion, it is important to dissect carefully just a small area necessary to
      anastomose a graft, and to take elaborate assistant measures.

PMID- 8992040
TI  - [A case of swallowed fish bone-induced esophageal perforation and mediastinitis
      treated with pedicled omental graft].
AB  - We experienced a case of 47-year-old man who suffered swallowed fish bone-induced
      esophageal perforation with purulent mediastinitis and underwent direct suture
      closure of the perforation and reinforcement with a pedicled parietal pleura four
      days after the onset. Postoperative esophageal suture insufficiency was occured
      and reoperation was performed two months after the first operation. The
      esophageal fistula was plugged with a pedicled omental graft successfully. The
      postoperative course of the patient was uneventful and he discharged 45 days
      after the second operation. A reinforcement by pedicled omental graft for
      esophageal rupture accompanied with mediastinitis was considered to be a useful
      procedure.

PMID- 8992041
TI  - [A case report of concomitant carotid and coronary artery reconstruction].
AB  - We reported a case of a 70-year-old female who underwent simultaneous carotid
      endarterectomy and coronary artery bypass surgery. Preoperatively, cardiac
      catheterization demonstrated three vessel coronary artery disease. Her carotid
      angiogram revealed a 90% stenosis in the left common carotid artery. The cerebral
      blood flow scintigram on acetazolamide stress detected severely reduced cerebral
      blood flow on her left anterior and temporal lobe. Her postoperative course was
      uneventful. Postoperatively, no reduced cerebral blood flow was detected on the
      acetazolamide stress image. In patients with significant carotid artery stenosis,
      the cerearal blood flow scintigraphy on acetazolamide stress was a useful method
      for the simultaneous carotid endarterectomy and coronary artery bypass surgery.

PMID- 8992042
TI  - [Three cases of coronary to pulmonary arterial fistulae combined with valvular
      disease].
AB  - Three cases of coronary to pulmonary arterial fistulae (CAF) combined with
      valvular disease are reported. The first case was 53-year-old male admitted with
      mitral stenosis (MS) and left atrium thrombus. CAF originating from both coronary
      artery and draining to pulmonary artery were found by coronary angiography. Open
      mitral comissurotomy (OMC), thrombectory and ligation of CAF were performed. Case
      2 was 52-year-old female suffered from CHF due to MS. Abnormal communication from
      left coronary artery to pulmonary artery was demonstrated. OMC and ligation of
      CAF were performed. Case 3 was 65-year-old male with combined valvular disease.
      MS, aortic regurgitation and CAF from right coronary artery to pulmonary artery
      were revealed. Mitral and aortic valve replacement and ligation of CAF were done.
      Diffusion of coronary angiography increase chance to reveal coronary artery
      fistulas during examination of acquired cardiac disease. Coronary artery fistulas
      draining into pulmonary artery were completely ligated by double ligation at both
      the arising point from coronary artery and the draining point to pulmonary trunk.

PMID- 8992043
TI  - [A case of ASD with SLE treated with Carmeda BioActive surface circuit in
      cardiopulmonary bypass system].
AB  - A 61-year-old woman of ASD complicated with SLE was operated on. We used a
      heparin coating Carmeda BioActive Surface (CBS) in cardiopulmonary bypass circuit
      for the purpose to prevent the postoperative complications due to the reduced
      complement activation by SLE. This system could prevent the decline of the
      reduced complement activation during cardiopulmonary bypass and after operation.
      The management of steroid therapy for SLE patient, usefulness of heparin coating
      CBS system for hypocomplement disease were discussed.

PMID- 8992044
TI  - [A case report of multiple pseudoaneurysms of the left ventricle following acute
      myocardial infarction].
AB  - Multiple pseudoaneurysms of the left ventricle following acute myocardial
      infarction were successfully repaired in a 50-year-old man. Three days after
      onset of acute myocardial infarction, we electively performed PTCA on the right
      coronary artery which was completely occluded at the proximal segment. One month
      after PTCA, the left ventriculogram revealed multiple pseudoaneurysms of the left
      ventricle. Primary closure of orifices of the pseudoaneurysms was performed using
      pledgeted mattress sutures under cardiopulmonary bypass. Histology of aneurysm
      confirmed the diagnosis of pseudoaneurysm.

PMID- 8992045
TI  - [Total repair of tetoralogy of Fallot in an adult: report of a case without prior
      treatment at 59 years of age].
AB  - We reported successful repair of tetoralogy of Fallot of a male case aged 59
      years old. There was no palliative operation prior to this correction. The
      preoperative clinical features were as follows: dyspnea on effort and at rest,
      cyanosis and clubbing, multiple cerebral thrombosis without symptoms. Polycytemia
      was remarkable at Hb 23.3 g/dl and Ht 73.8%. PaO2 was 39.2 mmHg and hypoxemia was
      recognized. CTR was 59% and pulmonary vascular shadows were decreased but
      bilateral pulmonary arteries were well developed. Cardiac catheterization showed
      that high RV systolic pressure equal to that of LV and severe RV outflow
      obstruction. Pulmonary artery was well developed (the diameter ratio of PA and
      aorta: 0.84). Collateral arteries to the pulmonary vascular system were not
      significant by aortography. The surgical procedures were performed under
      conventional method. Pulmonary valvular stenosis was released by comissurotomy
      and RV outflow tract obstruction was also released through minimal right
      ventriculotomy. The conus branch of coronary artery crossed the outflow tract, so
      that we preserved this artery for preventing right ventricular failure post
      operatively. There was no need to use trans-annular patch for reconstruction of
      the outflow tract. In post operative course, only a low dosage of catecholamin
      was required but no other special treatment was needed. Ventricular and
      supraventricular arrhythmia had appeared in short period but after administration
      of anti arrhythmic drugs, heart rhythm was converted to sinus rhythm easily.
      Pathological findings of RV muscle which resected at the operation showed marked
      fibrous degeneration and irregularity of cells, and it suggested that sever
      hypoxia and high pressure for long time affected the ventricular muscle. We
      concluded that even older patients of tetralogy of Fallot were corrected safely
      and were able to get good quality of life after operation.

PMID- 8992046
TI  - [Two cases of the successful treatment of TAPVR with asplenia syndrome in
      neonates and infants].
AB  - Two patients of asplenia syndrome with pulmonary venous obstruction underwent
      TAPVR repair in the period of neonate (14 days) and infant (49 days). Associated
      procedures were necessary to adjust pulmonary blood flow (central shunt in 1, PA
      banding in 1). Both patients required subsequent surgical procedures; right
      modified BT shunt, due to kinking of central shunt in one patient and rePA
      banding for reduction of pulmonary blood flow in another patient. One patient
      died 4 months after the first operation of arrhythmia. Another patient is doing
      well in 7 months after the first operation. The TAPVR repair in the early period
      of infant or naonate is necessary to prevent progress of pulmonary venous
      obstruction. Adjustment of pulmonary blood flow is important for management of
      patients of asplenia syndrome after TAPVR repair.

PMID- 8992047
TI  - [A case report of total cavopulmonary connection following total cavopulmonary
      shunt].
AB  - A 20-year-old man underwent total cavopulmonary shunt for univentricular heart
      type A (A.L.L.) with hemiazygos connection six years ago. Four years later, his
      condition deteriorated with easy fatigue and cyanosis. Cardiac catheterization
      showed recanalization of ligated SVC. Chest CT showed tight adhesion between the
      chest wall and the ascending aorta. We approached the heart through left
      anterolateral thoracotomy in order to avoid injury of the aorta and the ventricle
      during redo median sternotomy. Total cavopulmonary connection with intraatrial
      conduit was performed under circulatory arrest and retrograde cardioplegia
      without aortic cross clamp. His postoperative course was satisfactory. Left
      thoracotomy was useful for total cavopulmonary connection following total
      cavopulmonary shunt associated with postoperative adhesion.

PMID- 8992048
TI  - [Successful surgical repair of atrial septal defect associated with mitral
      regurgitation and tricuspid regurgitation].
AB  - A 63-year-old woman with atrial septal defect, mitral regurgitation, and
      tricuspid regurgitation underwent mitral valvuloplasty with 30 mm Carpentier
      ring, patch closure of atrial septal defect and tricuspid annuloplasty with 36 mm
      Carpentier ring. She was doing well now. In this case, preoperative
      catheterization showed left-to-right shunt ratio of 32% and right-to-left shunt
      ratio of 51%. The existence of right-to-left shunt was considered to be related
      to the grade of tricuspid regurgitation. It is concluded that in these cases,
      surgical repair should be recommended before the onset of severe progressive
      heart failure.

PMID- 8992049
TI  - [A case of so-called carcinosarcoma of the lung].
AB  - A 69-year-old male was followed at our institute for the purpose of hemo
      dialization. During follow-up, a tumor shadow (phi 6.5 x 7.0 cm) was found in rt.
      S5 by chest X-ray. This tumor was diagnosed as squamous cell carcinoma by TBLB.
      Right middle lobectomy (R 2 a) was performed. Histological staging was pT 2 N 2 M
      0, stage IIIa. This tumor was cystic, filled with keratin like substance.
      Histologically, the cyst wall was composed of well differentiated squamous cell
      carcinoma and sarcomatous stroma which didn't differentiate into bone, cartilage,
      muscle, and etc. Immunohistologically, sarcomatous stroma was positively stained
      by vimentin, negatively by keratin and EMA. This patient survived 7 months with
      recurrence.

PMID- 8992050
TI  - [Intrapulmonary lymph node diagnosed by thoracoscope: a case report].
AB  - A 62-year-old man was admitted to our hospital because of abnormal shadow on
      chest X-ray. Chest X-ray and CT showed a subpleural tumor 12 mm in diameter in
      the S8 segment of the right lung. Thoracoscopic observation revealed a subpleural
      black nodule. Wedge resection of the S8 segment was performed. Pathologically,
      the nodule was diagnosed as an intrapulmonary lymph node. It should be noted that
      thoracoscope was very useful for differentiation of intrapulmonary lymph node
      from other small malignancy.

PMID- 8992051
TI  - [Two cases of the congenital posterolateral diaphragmatic hernia were reported].
AB  - Case 1, a 9-year-old woman, was admitted to our hospital because of nausea,
      vomiting, and epigastralgia. Diagnosis of Bochdalek hernia was made by the
      unusual course of naso-gastric tube. At surgery through the left posterorateral
      thoracotomy, the herniation of the stomach, small intestine, and colon to the
      thoracic cavity through the dorsolateral defect of the diaphragm were revealed.
      Case 2, a 35-year-old man, was admitted to our hospital because of dyspnea.
      Similar diagnosis was made by the examination of upper G1 series and barium
      enema, which demonstrated the presence of multiple loops of the small intestine
      and colon in the left thoracic cavity. Their postoperative courses were
      uneventful. Most of Bochdalek hernia is observed in infancy, and adolescent or
      adult case is is rarely reported (approximately 10% of all cases). Since this
      often misdiagnosed as pleuritis or pulmonary tuberculosis, a cautious examination
      is necessary for the establishment of the correct diagnosis.

PMID- 8992052
TI  - [A case of intrathoracic goiter].
AB  - Intrathoracic goiter is an uncommon conditional lesion. A case of intrathoracic
      goiter in a 66-year-old woman is herein described. Her chief complaint was
      anterior chest opplession. A computed tomographic scan and magnetic resonance
      imaging (MRI) revealed intrathoracic goiter pressed the trachea to the right
      side. The tumor was safety and completely took by collar incision without
      thoracotomy. Histologically, the mass was diagnosed the adenomatous goiter. In
      this case, MRI was very useful to be determined the surgical approach.

PMID- 8992053
TI  - [Endocavitary echography following abdominoperineal extirpation of the rectum].
AB  - Transrectal echography using a high-frequency transducer is a well established
      method for preoperative rectal carcinoma assessment, and for postoperative follow
      up of patients with anterior resection for rectal carcinoma. Having in mind the
      impossibility for follow-up study of patients with abdominal perineal extirpation
      of the rectum by transrectal echography, a new pattern of application of the
      transducer employed for endorectal examination is suggested. In five patients (4
      women and 1 man) endocavitary echography through the anal canal is done. In women
      the examination is supplemented by transvaginal echography. A local recurrence in
      the course, of transvaginal study is recorded in one patient. The technique of
      examination and the superiorities of the procedure are discussed.

PMID- 8992054
TI  - [The factors determining survivorship in patients with colorectal carcinoma
      complicated by obstructive ileus of the large intestine].
AB  - A total of 232 patients with obturation ileus, caused by locally advanced
      colorectal carcinoma, are operated over a 12-year period (1979-1990). In 160
      patients (68.97 per cent) the tumor is located in the colon, and in 72 (31.03 per
      cent)-in the rectum. The operative interventions performed are distributed as
      follows: 122 (52.58 per cent) radical, and 110 (47.42 per cent) palliative. There
      are 84 patients (36.03 per cent) in IV clinical stage. Postoperative lethality
      among those subjected to radical operation amounts to 25.41 per cent, with
      leading underlying causes-peritonitis (35.08 per cent) and serious ileus
      intoxication (21.05 per cent). The survival over 1, 3 and 5-year periods among
      those radically operated is 74.59, 48.37 and 34.06 per cent, respectively.
      Histologically differentiated adenocarcinoma is demonstrated in 69.38 per cent,
      undifferentiated-in 17.50 per cent, and mucinous adenocarcinoma-in 13.12 per
      cent. The factors with a high prognostic value include: stage of primary tumor
      development, lymph involvement, type of operative intervention and histological
      variant of the neoplasm.

PMID- 8992055
TI  - [Postoperative peritonitis].
AB  - This is a report on retrospective summed-up analysis of the therapeutic approach
      to 296 patients presenting postoperative peritonitis (PP). They account for 1.4
      per cent of the total number of patients operated on in the clinic. The latter
      percentage differs in the single groups of patients, distributed by organic
      localization of the pathological process, as follows: 1.3 per cent in
      hepatobiliary and pancreatic diseases, and 1.9 per cent in gastroduodenal ones.
      In colorectal diseases the percentage grows to 8, and after the 80th year of life
      it falls to and below 4, amounting to 2.2 per cent during the last five years.
      The overall mortality rate is 69 per cent--57.7 and 72.5 per cent respectively
      for the three separate groups-mainly at the expense of patients presenting
      oncological diseases, 73.5 per cent. The underlying causes of PP development
      comprise: insufficiency of the anastomosis, intraoperative contamination and
      infection of the abdominal cavity, intraoperative oversights-technical errors,
      iatrogenic and foreign body, circulation derangement in the organ operated on,
      suture applied to cancer infiltrated and infected tissue and persisting
      peritonitis for which the intervention is undertaken. The diagnosis is difficult
      regardless of the biochemical, instrumental and microbiological examinations
      performed. Early relaparotomy is the only possible life-salvaging approach to the
      patient, its immediate goal being sanation of the source, peritoneal lavage, wide
      drainage and ileostomy. PP remains a problem difficult to handle irrespective of
      the progress of antibiotic and resuscitation treatment.

PMID- 8992056
TI  - [The possibilities for predicting the course and outcome in peritonitis
      patients].
AB  - Based on a retrograde study of clinical case material, covering the period 1989
      1993, and MPI modification, a coefficient of correlation = 0.661054 and standard
      error = 0.297438 are calculated for all peritonitis patients, whereas in those
      where all examination criteria are available the coefficient of correlation =
      0.742431 and the standard error = 0.344041. This enables high-degree
      prognostication, as early as during the operation, of the course and outcome of
      treatment in each individual patient, and accordingly, resorting to a more
      aggressive tactics and procedures in the patients at risk.

PMID- 8992057
TI  - [The induction of lipid peroxidation in the serum of patients with acute
      peritonitis].
AB  - The level of lipid peroxidation products in the sera of patients with acute
      peritonitis and clinically healthy blood donors are studied. An increase in the
      level of TBA-reactive substances is documented in the acute peritonitis group-
      twice as high as compared to clinically healthy blood donors. Changes in the
      patients in toxic and terminal phases of peritonitis are rather significant.
      Following hemofiltration, the serum lipid peroxidation products are decreased in
      comparison with the pre-hemofiltration state.

PMID- 8992058
TI  - [Combined trauma--an analysis of a 10-year period].
AB  - Proceeding from retrospective analysis of 1802 casualties presenting open and
      closed combined trauma (CT), treated in the Emergency Medicine Institute
      "Pirogov" over the period 1985 through 1994, attention is focused on the changes
      in incidence and patterns of associated injuries. Problems relating to
      organization of the treatment of such patients at the various stages are
      discussed. The basic requirements of diagnosing and establishing the indications
      for operation are outlined from the standpoint of general surgery. Finally, the
      main developmental trends of the therapeutic approach to CT, and the possible
      ways to find a solution of the most important problems along this line are summed
      up.

PMID- 8992059
TI  - [Laparoscopy and laparoscopic echography in the diagnosis and staging of
      gastrointestinal carcinomas].
AB  - The clinical relevance of laparoscopy (LS) and laparoscopic echography (LSEG) in
      diagnosing and staging gastrointestinal carcinomas is assayed in the light of
      diagnostic methods in current use. The study covers 257 patients undergoing LS,
      and 23-LSEG. For the purpose a rigid 7.5 MHz echolaparoscopic probe is used. In
      16 per cent of the cases LS fails to resolve the basic diagnostic problems faced,
      whereas in 35 per cent it alters completely the preliminary clinical diagnosis.
      In over 90 per cent of cases LSEG supplements or modifies the laparoscopic
      diagnosis. Emphasis is laid on the role played by LSEG in defining the loco
      regional stage of gastric and colorectal carcinomas, as well as on the
      contribution of the method to establish pancreatic carcinomas not lending
      themselves to resection. What is more, LSEG demonstrates inoperable cases by
      detecting small, unsuspected metastases, not prominating above the hepatic
      surface.

PMID- 8992060
TI  - [Intraoperative abdominal echography].
AB  - Experience with and the impressions of adopting intraoperative abdominal
      echography in eighteen patients, aged 26 to 73 years, 9 men and 9 women, are
      shared. The distribution of patients by pattern of diseases is as follows:
      colorectal carcinoma--4 cases, liver echinococcus--one, gastric carcinoma--one,
      hepatocellular carcinoma--one, cholangitis acuta purulenta-one, echinococcus of
      lung and liver--one, calculous cholecystitis with choledocholithiasis--five, and
      carcinoma of ductus choledochus--one. Fifty intraoperative abdominal echographies
      and one intrathoracic supradiaphragmatic echography of the liver are performed.
      Intraoperative abdominal echography of tumors involving organs of the digestive
      tract contributes to specify the staging of the neoplastic process. In liver
      echinococcus it determines precisely the number of cysts and diagnoses impalpable
      cystic formations, while in choledocholithiasis it documents the presence of
      calculi in the biliary tracts and eventual dilatation of intrahepatic ones. In
      five patients intraoperative abdominal echographic is done in conjunction with
      intraoperative fiber choledochoscopy.

PMID- 8992061
TI  - [Peritonitis--an unaging problem in surgery].

PMID- 8992062
TI  - [Complicated colorectal cancer--new trends in its diagnosis and surgical
      treatment].
AB  - Colorectal carcinoma is among the commonest cancer diseases of the alimentary
      canal in this country. The morbidity and mortality rates show an increase on an
      annual basis. A total of 1094 patients presenting colorectal carcinoma are
      analyzed over the period 1985 through 1996. In 690 cases (63.1 per cent) a
      complicated form of the basic disease is established. For the first time in this
      country, assessment of the total amount of bile acids in feces using thin-layer
      chromatography is done, as well as of cholesterol, beta-lipoproteins and
      triketosteroids in the serum. As shown by the investigations, there is a
      correlation between increased bile acid concentrations in the feces, decreased
      values of serum cholesterol, high concentrations of triketosteroids and severe
      dysbacteriosis, revealing in turn new aspects in the etiopathogenesis, early
      diagnosis and prophylaxis against colorectal carcinoma. The new principles of
      surgical management in complicated colorectal carcinoma improve considerably the
      5-year survivorship, amounting to 22.1 per cent for T4.

PMID- 8992063
TI  - [Stomach carcinoma--the current trends in its surgical treatment].

PMID- 8992064
TI  - [A case of carcinoid of the large intestine with an atypical course and rare
      location].

PMID- 8992065
TI  - [2 cases of acute suppurative segmental sigmoiditis].

PMID- 8992066
TI  - [Quo vadis surgical ophthalmology?].

PMID- 8992067
TI  - [Minimizing astigmatism by controlled localization of cataract approach with the
      no stitch technique. A prospective study].
AB  - BACKGROUND: The no-stitch-technique with deliberate localisation of the cataract
      incision is a method to reduce the postoperative astigmatism. This prompted us to
      investigate the postoperative astigmatism with varying incision localisation; our
      aim is to achieve a postoperative astigmatism < or = 1.0 D. PATIENTS AND METHOD:
      In this study we controlled 319 eyes of 316 cataract patients. We took into
      consideration the preoperative astigmatism and operated in the 12 o'clock or
      lateral position. The astigmatism was measured by an ophthalmometer
      preoperatively, on the first day, after 3-5 months and 8-12 months after surgery.
      RESULTS: A preoperative astigmatism of up to < or = 1.0 D was present in 82.4% of
      eyes. On the first day after surgery an astigmatism of < or = 1.0 D was present
      in 89.3% of eyes. After 3-5 months postoperatively astigmatism was < or = 1.0 D
      in 97.2% and in 98.8% after 8-12 months postoperatively. 15.7% of patients showed
      a preoperative astigmatism between 1 and 2 D, but only 1.2% after 8-12 months.
      There was no astigmatism > 2.0 D after 3-5 months and 8-12 months (preoperative
      2%). CONCLUSIONS: The no-stitch-technique permits to control the postoperative
      astigmatism with deliberate localisation of the cataract incision. Postoperative
      astigmatism appeared to be stable. We therefore recommend for preoperative "ATR
      (Against the rule)-Astigmatism" (> or = 1.0 D) operation in lateral position and
      for preoperative "WTR (With the rule)-Astigmatism" operation in the 12 o'clock
      position.

PMID- 8992068
TI  - [Comparison of classical keratometry and computer-assisted corneal topography in
      high grade postoperative astigmatism after perforating keratoplasty].
AB  - The standard keratometry measures the central corneal refractive power by only
      four sample points. there is a risk for poor or incorrect measurements in high
      irregular postoperative astigmatism following penetrating keratoplasty. Therefore
      we compared the standard keratometry with the computer assisted corneal
      topography. METHOD: In the study 43 consecutive measurements after penetrating
      keratoplasty, with an astigmatism > 4 dpt measured with standard keratometry
      (Zeiss Ophthalmometer), were analyzed. A computer assisted corneal topography
      (Eye Sys) was performed simultaneously. 22 measurements were received before, 21
      measurements after T-incisions. The astigmatism value and axis measured by
      keratometry and corneal topography were compared and the correlation coefficient
      were calculated. As a simple index for the asymmetry of the resulting corneal
      cylinder measured by corneal topography, the frequency and the axis difference of
      both steep hemimeridians within the 3 mm zone were determined. RESULTS: The
      astigmatism values measured by standard keratometry (8.1 +/- 2.7 dpt) were
      significantly higher than the values measured by the computer assisted corneal
      topography (6.1 +/- 2.2 dpt). The difference of the cylinder axis measured by
      standard keratometry and corneal topography was 19 +/- 23 degrees; 10 +/- 15
      degrees before and 29 degrees +/- 26 degrees after T-incision. The comparison of
      the astigmatism values showed a correlation coefficient of 0.82 in the total
      group, of 0.84 before and of 0.83 after T-incisions. In 26% of all measurements
      the axis difference of both steep hemimeridians (3-mm zone) was more than 30
      degrees. After T-incisions this difference increased. CONCLUSIONS: Based on the
      results of this study, it seems reliable to identificate patients with high
      postoperative astigmatism following penetrating keratoplasty by standard
      keratometry.

PMID- 8992069
TI  - [Fluorescence angiography of the anterior eye segment in severe eye chemical
      burns].
AB  - BACKGROUND: Severe eye burns usually result in extensive necrosis of the
      conjunctiva and subconjunctival tissue. To reduce the reactive inflammatory
      response excision of the necrotic tissue is necessary. PATIENTS AND METHOD:
      Between August 1990 and December 1994 fluorescein angiograms of the anterior eye
      segment were performed in 13 (17 eyes) patients with most severe eye burns. The
      angiographies were carried out 1-4 days after the accident. Conventional photo
      angiography was performed using a fundus camera (NF 505-AF Nikon). RESULTS: The
      angiograms revealed characteristic patterns that provided exact information on
      the perfusion of burned conjunctival and underlying tissue. It was particularly
      useful in the detection of clinically not recognisable subconjunctival ischemia.
      In addition, perfusion of the episcleral vessels and the extent of scleral
      ischemia could be quantified. According to the angiographic findings subtile
      excision of the necrotic tissue was performed and vascularized tissue was
      preserved. CONCLUSION: Anterior segment angiography is a valuable method in
      assessing the extent of necrosis of the conjunctiva and underlying tissue and in
      determining scleral ischemia. It provides a basis for deciding the extent of
      surgical debridement of necrotic tissue in the acute phase of the burn. The
      quantification of limbal and scleral ischemia may give useful information for
      early plastic-reconstructive procedures.

PMID- 8992070
TI  - [Correlation between prognostically predicted and actually attained refraction].
AB  - BACKGROUND: In cataract surgery high quality is demanded. That is why high
      precision in calculation of IOL power is necessary for predicting postoperative
      refraction. MATERIALS AND METHODS: In a series of 103 patients the predicted
      refraction--calculated by the SRK II formula for only one type of IOL (A-constant
      118.9)--was compared to the received early and late (3 month) postoperative
      refraction. RESULTS: The accuracy of IOL calculations in 95% was acceptable-
      within a range of 2 diopters. The prediction errors of extended values were only
      shown in cases of axial length of more than 26 millimeters. CONCLUSIONS: The
      results confirm the fact that by means of SRK II formula the accuracy of IOL
      calculation is satisfactory in respect of predicted refraction. In eyes of
      elongated axial length the accuracy is limited.

PMID- 8992071
TI  - [Optical sector iridectomy: an alternative to perforating keratoplasty in Peters'
      anomaly].
AB  - BACKGROUND: The penetrating keratoplasty as an early surgical procedure to
      present deep irreversible amblyopia in patients suffering from Peters' anomaly
      has shown an extremely high risk for transplantat failure. PATIENTS AND METHODS:
      From 1980 to 1992 20 sectoriridectomies (6 bilateral, 1 twice because of
      progressive corneal opacification in the area of sectoriridectomy) were performed
      in 13 patients with Peters' anomaly (diameter of corneal opacification greater
      than half of the corneal diameter). The mean age at surgery was 1 year and 9
      months, the mean follow-up was 3 years and 6 months. Preoperatively the visual
      function was uncertain light perception in all eyes with marked horizontal
      nystagm. Except for two eyes (24 mm Hg) the intraocular pressure (IOP) was
      normal. RESULTS: In 9 (47%) eyes the visual acuity was 20/500 to 20/200. One eye
      showed certain light fixation, one eye hand movement. In one eye the visual
      function remained uncertain light perception "after combined lens aspiration."
      One eye developed a phthisis after combined anterior vitrectomy and lens
      aspiration for PHPV. In three eyes, the visual outcome could not be determined
      certainly, in three eyes, the follow-up failed. In two eyes the IOP was regulated
      under topical antiglaucomatous eye drops, in the other eyes the IOP was normal.
      CONCLUSIONS: In contrast to penetrating keratoplasty sectoriridectomy seems not
      to be followed by secondary glaucoma postoperatively. The visual outcome is
      comparable to that after early keratoplasty. We recommend "optical"
      sectoriridectomy as an alternative surgical approach to early penetrating
      keratoplasty in patients suffering from Peters' anomaly.

PMID- 8992072
TI  - [Effect of corneal astigmatism on contrast sensitivity in mono- and multifocal
      pseudophakia--a theoretical study of the physical eye].
AB  - BACKGROUND: Several clinical studies indicate, that the visual function of
      multifocal IOLs (MIOL) is impaired by corneal astigmatism. To assess the
      influence of uncorrected corneal astigmatism on the contrast sensitivity function
      (CSF) of mono- and multifocal IOLs, an "optical implantation" of physical eyes
      with astigmatic corneas and IOLs was performed in younger subjects. METHODS: The
      virtual image of physical eyes with a 40 dpt achromate as artificial cornea and
      the (M)IOL in a water bath was projected on the retina of the observer by means
      of an exactly adjusted video objective. Silicone lenses with defined astigmatisms
      (+1; +2; +4; +6 dpt) were put in front of the achromate to produce an artificial
      corneal astigmatism. We compared results of a standard monofocal IOL (Pharmacia
      811B), a multizone progressive MIOL (AMO Array SSM-26NB) and a diffractive MIOL
      (Pharmacia 811E). CSF through these IOLs in the physical eyes was measured in ten
      healthy subjects (mean age: 27.4 y.) with the B-VAT II-SG Video Acuity Tester
      (Mentor O&O), which uses sine wave gratings of five different spatial frequencies
      (1.5; 3; 6; 12; 20 cpd). RESULTS: Without astigmatic lenses, all IOLs showed a
      mean CSF within the age-related norm, but the monofocal IOL yielded significantly
      better results than both MIOLs at three spatial frequencies (3; 6; 12 cpd). With
      additional astigmatic lenses of 2 dpt and more, mean CSF of all IOLs was below
      normal range, but there was no difference in the performance of the three lens
      styles. CONCLUSION: CSF of MIOLs seems to be less sensitive to uncorrected
      corneal astigmatism than CSF of the monofocal IOL. This suggests, that a higher
      preoperative astigmatism does not severely affect the image quality through a
      multifocal IOL.

PMID- 8992073
TI  - [The microtrephine: experimental experiences, initial clinical application].
AB  - INTRODUCTION: In some diseases of the cornea, histopathological or
      microbiological evaluation of a stromal samples is essential. On the other hand
      one of the main aims in the therapy is to keep the cornea clear and without
      scars. Until now bioptic techniques were not suitable for both aims, getting a
      sample with minimal damage of the cornea. There was a lack of a method for
      corneal biopsy which is clinically easily applicable. MATERIAL: We developed a
      new instrument for taking corneal biopsies. It is a microtrephine with 160
      microns diameter rotating with 30,000 Rpm. It takes biopsies of corneal
      epithelium and stroma as solid cylinders. The biopsy is non traumatic, safe and
      repeatable. Biopsies were taken until now on 32 alkali burnt rabbit corneas, 8
      enucleated human corneas and 5 patients. RESULTS: 157 biopsies were taken until
      now. In 75% a sample could be gained. The perforation rate was 0.63% in rabbits.
      No perforation occurred until now in human corneas. Preparations of light-,
      scanning- and transmission electron microscopy are presented in this paper for
      demonstrating examples of application. Microbiological preparations of corneal
      infiltrates were sterile up to now, representing sterile technique with this new
      instrument. Herpes simplex PCR was positive in one out of six stromal biopsies
      from one cornea in supposed herpes keratitis. CONCLUSION: With the microtrephine
      samples of the corneal stroma can be taken with high precision. A wide variety of
      routine diagnostics including repeated measurements on stromal samples of a
      single cornea are possible now. Early bioptic diagnostics of corneal diseases can
      be achieved now.

PMID- 8992074
TI  - [Expert assessment of initial surgical management after experimental chemical eye
      burn].
AB  - BACKGROUND: Initial surgical treatment of severe eye burns is important for the
      long lasting healing period. To look closer at the efficacy of the early surgical
      treatment and the possible consequences for woundhealing, the surgical
      interventions were examined in an animal experiment. MATERIALS AND METHODS: The
      right eye of 20 rabbits each was burned with 1 n NaOH for 30 seconds followed by
      a surgical treatment 48 hours later. In the first study necrosectomy,
      tenonplasty, application of an artificial epithelium and blepharoplasty was
      withdrawn and the fornices were prevented from cicatrization by mechanical
      treatment treatment with blunt spatula. Antiinflammatory depotinjection of Volon
      A 40 was applicated additionally. After an interval of 4-18 weeks the eyes were
      examined histologically. RESULTS: A higher risk for infections could be observed
      in eyes which underwent blepharorhaphy. Furthermore proliferative processes and
      corneal ulcerations were predominant. In contrast to these findings the latter
      complications could be prevented due to the clinical inspection of the artificial
      epithelium and described mechanical irritation of the fornices in the second
      study. DISCUSSION: It could be shown that proliferative processes are major
      complications after severe burns of the eye. Nevertheless the intensity could be
      minimized by the consequent therapy. Furthermore it could be demonstrated that
      the artificial epithelium is an effective tool providing good prognosis for
      subsequently planned keratoplasty. To enable necessary postoperative inspection
      blepharoplasty should be avoided.

PMID- 8992075
TI  - [Dosage problems in suspension eyedrops].
AB  - PURPOSE: In opthalmic suspensions, the mean dose and the uniformity of amounts
      administered in single drops depend upon the redispersibility of drug particles
      by shaking. The present article is a contribution to the development of the
      experimental and theoretical basis for a reproducible test, by which the dose
      uniformity of suspension eyedrops can be assessed under therapeutically relevant
      conditions. The requirement that suspension eyedrops and similar dosage forms
      should be redispersable after sedimentation upon storage is stated in the
      monographs on eyedrops of the German Pharmacopoeia and can be found in similar
      contexts in other pharmacopoeias. Until now, however, no corresponding test
      method has been specified. METHODS: Shaking profiles were recorded in 31 subjects
      and 27 patients using an acceleration sensor. They were compared with the
      acceleration profile of a computer-controlled pneumatic shaker and sampler. Both
      frequency and intensity of the shaking action were quantified by Fourier analysis
      of the acceleration profiles. The drug content of single drops of Isopto-dex
      (0.1% dexamethasone), Chibro-Amuno 3 (1% indomethacin), and Inflanefran-forte (1%
      prednisolone acetate) was assessed exhaustively in four 5-ml specimens of each
      ophthalmic suspension using the apparatus. The dose uniformity of single drops of
      suspension eyedrops was measured by UV-spectrophotometry for the entire contents
      of bottles. Four samples per day were drawn after six shaking cycles for
      approximately 4 weeks with three intervals of 4 h during daytime and 1 interval
      of 12 h during the night. RESULTS: The shaking intensity of patients was lower
      than that of healthy subjects, while the frequency was similar for both groups.
      The intensity of the apparatus corresponds to the 67th percentile of the patients
      and to the 18th percentile of the healthy subjects. It was sufficiently close to
      the central values of both distributions to allow comparisons. for Isopto-dex,
      the mean drug content of 9.5 microns per drop amounted to only 25% of the value
      expected after complete redispersion, with a coefficient of variation (CV) of
      23%. The mean value for Chibro-Amuno 3 was 93% of the expected quantity of
      indomethacin with a CV of 34%, while the mean content of Inflanefran-forte drops
      was 95% of the labelled dose with a CV as low as 9%. CONCLUSION: The drug content
      of single drops of ophthalmic suspensions can be studied under well-defined and
      reproducible conditions by means of a computer-controlled pneumatic shaking and
      sampling apparatus. Under the conditions prevailing in this study, the solidified
      sediment of Isopto-dex was incompletely redispersed, so that doses were
      significantly too low. A variable dosing pattern with acceptable mean was
      observed for Chibro-Amuno 3, while the results for Inflanefran-forte were fully
      satisfactory.

PMID- 8992076
TI  - [Retinal necrosis after blunt bulbus trauma].
AB  - BACKGROUND: Acute retinal necrosis is a rare complication of blunt eye injury. We
      report about a patient with this type of retinal break. PATIENT: A 20-year-old
      male was referred to our hospital after a blunt injury of his left eye due to a
      ball. Visual acuity was 1.0 and the anterior segment was completely normal. A
      large retinal necrosis surrounded by a Berlin edema was present in the upper
      temporal part of the globe. A partial retinal detachment was present. The retina
      reattached within two weeks without further treatment and a characteristic
      granular hyperpigmentation developed. The edge of the retinal break was treated
      by photocaogulation. CONCLUSION: The affected patient was young and had a solid
      vitreous, providing internal tamponade of the retina in spite of a large retinal
      break. In these patients, the clinical course of an acute retinal necrosis after
      blunt injury should be waited for. However, a retinal detachment that persists
      after retinal edema disappeared is caused by pathologic vitreous changes and
      requires surgical treatment.

PMID- 8992077
TI  - [Orbital myopathy in metastatic malignant paraganglioma: a paraneoplastic
      syndrome?].
AB  - BACKGROUND: Several disease entities of the orbit are known which display an
      autoimmunological pathogenesis. Among these disease entities the thyroid-related
      immune orbitopathy and the idiopathic orbital inflammatory syndrome (orbital
      pseudotumor). The pathogenesis of these diseases is not well understood; however,
      an autoimmune inflammatory reaction histologically characterized by a chronic
      inflammatory cell infiltrate has been suggested. One care of orbital pseudotumor
      presumably of paraneoplastic origin occurring in a patient with a non-Hodgkin's
      lymphoma has been reported. We report a patient with a metastatic paraganglioma
      and a proptosis secondary to enlargement of all extraocular muscles. CASE REPORT:
      A 52-year-old woman presented with a recent decline in visual clarity of her left
      eye and diplopia. Two years ago, the diagnosis of a hormonally inactive
      paraganglioma has been made. Ophthalmologic examination displayed a lagophthalmos
      caused by a right-sided facial paralysis secondary to a cerebral metastasis and a
      bilateral enlargement of all extraocular muscles. Curative therapy for the
      paraganglioma was not available. Palliative therapy as well as a high-dose
      corticosteroid therapy for the orbitopathy was refused by the patient. The
      patient died 18 months later. DISCUSSION: Our patient developed orbital changes
      similar to thyroid-related immune orbitopathy; however, there was no dysfunction
      of the thyroid. We believe that the orbital changes were a paraneoplastic immune
      reaction caused by the metastatic paraganglioma. We recommend that in patients
      who do not conform to the prototypical profile of well-known orbital disease
      entities should undergo further testing to exclude a remote neoplasm.

PMID- 8992078
TI  - [Fuchs' heterochromic cyclitis. Clinico-histopathologic findings of nodular
      iritis].
AB  - BACKGROUND: Despite the fact that in 1906 Fuchs described the first case of
      Fuchs' heterochromic cyclitis histopathologic reports of this disease are still
      rare. PATIENT AND METHODS: A clinicopathologic correlation of findings in Fuchs'
      heterochromic cyclitis is presented. In a patient with a history of Fuchs'
      heterochromic cyclitis for 15 years a secondary open-angle glaucoma developed.
      Several operations were performed including intracapsular cataract extraction,
      goniotrephanation (Elliot) and repeated cyclocryotherapy. The eye finally had to
      be enucleated because of a painful absolute glaucoma. RESULTS: Clinical hallmarks
      of Fuchs' heterochromic cyclitis in this patient include cataract formation and
      secondary open-angle glaucoma. Histology revealed accumulations of mononuclear
      cells on the surface of the iris and the corneal endothelium, as well as sparse
      inflammatory cells within the anterior chamber. The trabecular meshwork showed an
      infiltration of mononuclear inflammatory cells, chiefly lymphocytes and plasma
      cells. DISCUSSION: Accumulations of mononuclear cells on the surface of the iris,
      which histopathologically have not been described before, could represent the
      clinicopathologic correlate of Koeppe and Busacca nodules. Histologically, the
      cell deposits on the iris were similar to those in the anterior chamber and to
      larger corneal precipitates. It is supposed that the cells, which originally
      emigrated from the iris vessels, may form primary cell deposits on the iris
      surface or endothelium. Such iris precipitates may also be secondarily attracted
      by the endothelium in whole. An autoimmune-reaction against the corneal
      endothelium may be the underlying reason.

PMID- 8992079
TI  - [Digital fluorescein angiography in follow-up of the clinical course in therapy
      of patients with central vein occlusion and cystoid macular edema].
AB  - BACKGROUND: Fluorescein angiography with a scanning laser ophthalmoscope allows
      the quantification of morphologic and dynamic changes in the retina. In two
      patients with central retinal vein occlusion we monitored the progression of the
      cystoid macular edema (CME) and changes of microcirculation with a follow up of 4
      to 6 months. MATERIALS AND METHODS: Two patients with central retinal vein
      occlusion and CME were examined by means of digital fluorescein angiography.
      Arteriovenous passage times and macular capillary blood velocities in combination
      with quantifications of the macular angioarchitecture and the extent of the CME
      were evaluated. RESULTS: Hemodilution therapy improved retinal circulation,
      whereas macular circulation and the severity of the CME remained unchanged. With
      persisting CME oral acetazolamid therapy was initiated. Oral Acetazolamide led to
      resorption of the cystoid edema in tandem with improved macular circulation. The
      capillary density was altered but remained unchanged over time. CONCLUSIONS: By
      means of digital analysis of fluorescein angiograms a detailed monitoring and
      retinal and macular dynamics, macular morphology is possible. In these two cases
      CME improved after Acetazolamide and moreover retinal circulation returned to
      normal conditions.

PMID- 8992080
TI  - [Voluntary control of unilateral strabismus sursoadductorius].
AB  - BACKGROUND: Strabismus with unilateral elevation in adduction is an upward
      deviation of the adducting eye of unknown, not necessarily paretic origin. The
      term "old trochlear palsy" may be erroneous since the hypertropia is not
      necessarily larger in downward gaze and a causative lesion can usually not be
      identified. We describe here a marked voluntary influence on unilateral elevation
      in adduction, in situations that exclude binocular fusion. PATIENTS: Two patients
      with an elevation in adduction of the right eye and a positive head-tilt
      phenomenon, a 21-year-old and a 28-year-old man, were able to vary their vertical
      angle of squint at will. Even under artificial conditions that exclude binocular
      fusion (alternate cover test, dark-red glass test) could they change their right
      over-left deviation, Patient 1 between 4 and 20 degrees and Patient 2 between 0
      and 15 degrees. Under natural viewing conditions both patients had binocular
      vision with stereopsis that decompensated only when they looked to the left.
      CONCLUSIONS: We assume that our two patients had a "motor memory" that stores the
      muscle innervation for parallel eyes, i.e. the innervation suitable for binocular
      vision, and that the patients made use of or neglected this memory at will. In
      general, our observations suggest that a variable recourse to such a motor memory
      explains why, in patients with unilateral elevation in adduction, the angle of
      squint often changes. A voluntary access to this memory may, however, be
      exceptional.

PMID- 8992081
TI  - [Differential diagnosis of rapidly growing tumors--granuloma teleangiectaticum
      sive pyogenicum].
AB  - A clinicopathologic study of a granuloma telangiectaticum is reported in 37 year
      old-woman. The tumor has a reddish to white colorit. Its rapid growth, within 2
      weeks and appearance as well as clinical examination suggested a neoplastic
      process (squamous cell carcinoma). The patient had no trauma or surgery. The
      histopathological examination revealed a granuloma telangiectaticum. Local
      excision was curative.

PMID- 8992082
TI  - [Oncocytoma of the conjunctiva].
AB  - A 72-year-old woman presented with a lesion in her right eye, which had developed
      over 2 years. The cherry red lesion was located in the bulbar conjunctiva in the
      area of the plica semilunaris. Ophthalmologic examination was otherwise normal.
      Differential diagnosis included a pyogenic granuloma and a hemangioma. Excision
      of the tumor was performed. Histological examination revealed solid nests and
      cords of polyhedral cells exhibiting abundant, finely granular acidophilic
      cytoplasm and round to oval paracentral nuclei usually containing a single
      prominent nucleolus. The diagnosis of oncocytoma was established. Ocular
      oncocytomas are rare neoplasms and are mostly found in the caruncle. A location
      in the bulbar conjunctiva is extremely rare and only two reports are found in the
      literature with both of these located in the plica semilunaris.

PMID- 8992083
TI  - [Annual meeting of the Berlin-Brandenburg Ophthalmological Society. 2-3 December
      1995 in Berlin. Abstracts].

PMID- 8992084
TI  - [Viscoelastic substances in cataract surgery. Principles and current overview].
AB  - The major aim for the application of viscoelastic substances in cataract surgery
      is prevention of corneal endothelial cell loss. This aim is fulfilled by
      deepening of the anterior chamber, mechanical endothelium protection against
      surgical trauma, absorption of ultrasound energy, and coating of intraocular
      lens. The first and mostly used viscoelastic in ophthalmic surgery is a 1%
      solution of sodium hyaluronate (NaHA) with a molecular weight of 4 million
      daltons, and a viscosity of 229,000 cP (Healon). For this substance, a good
      endothelium-protecting function in cataract surgery, especially
      phacoemulsification, is documented in the literature. In the meantime, further
      NaHA solutions of different concentrations and viscosities, and a mixture of
      chondroitin sulfate and NaHA are being offered, as well as low-viscosity
      solutions of hydroxypropylmethylcellulose (HPMC). The different rheological
      properties (viscoelasticity, viscosity, and pseudoplasticity) of the substances,
      the pertinent differences in surgical behavior (injectability, ease of aspiration
      and manipulation), and the viscoelastic side-effects (mainly IOP increase) are
      described.

PMID- 8992085
TI  - [Fundus-oriented perimetry. Evaluation of a new visual field examination method
      for detecting angioscotoma].
AB  - BACKGROUND: Conventional automated perimeters usually work with a given set of
      grids and thus are normally not adapted to individual conditions. This fact
      restricts efficiency of this method not only for any single examination but also
      for follow-up studies. MATERIALS AND METHODS: A new method (patent pending) is
      introduced which superimposes an individual perimetric grid--corrected in respect
      to orientation, position and size--onto a patient's fundus image. A recently
      developed software realizes this procedure in a comfortable manner: the digitized
      fundus image is loaded into the computer by e.g. photo-CD or disc, depicted on a
      control monitor and mirrored if necessary. Assuming a central fixation, the
      foveola is translationally shifted to the center of the perimetric grid by the
      help of a crosshair. The blind spot which has been previously determined with
      kinetic perimetry is then superimposed onto the optic disc of the fundus image
      using a rotation and zoom function. In this way, it is possible to adapt the
      perimetric grid directly to the underlying individual fundus findings: thus,
      stimuli can be spatially concentrated or more frequently tested in special
      regions of interest. Additionally, test points can be dragged away from delicate
      positions to avoid artifacts. Examinations were carried out on a high resolution
      colour VDU of the Tubingen Electronic Campimeter (TCC). Alternatively, suited
      bowl perimeters can be used. RESULTS: In order to test the precision of the
      superimposing procedure, fundus oriented perimetry was performed to detect
      angioscotomata in 13 ophthalmologically normal subjects. Using dark stimuli
      (12'), visual field defects in the expected region, caused by retinal vessels,
      could be detected in 7 cases (= 54%). The resulting attenuation of differential
      light sensitivity in this circumscribed region was up to 12 dB. CONCLUSIONS: By
      means of a morphologically adapted, individual arrangement of stimulus locations
      fundus-oriented perimetry enables detection of even minute (angio-) scotomata.

PMID- 8992086
TI  - [Indications for eye examination of HIV patients--screening parameters for
      cytomegalovirus retinitis].
AB  - BACKGROUND: To reduce the burden of frequent visits at the physician we have
      checked (I) for which ocular manifestations in HIV-infection screening of
      asymptomatic patients is worthwhile and (II) which parameters may indicate
      patients at risk for CMV-retinitis. PATIENTS AND METHODS: The clinical data of
      215 HIV-infected patients were analyzed retrospectively. Only those ocular
      manifestations were considered suitable for screening that (a) endanger vision,
      (b) are treatable, (c) can be diagnosed sufficiently early and (d) are common.
      Furthermore (1) CDC-stage, (2) CD4+ count, (3) HIV-retinopathy, (4) CMV-uria and
      (5) CMV-antibodies were checked for their usefulness in indicating patients at
      risk for CMV-retinitis. RESULTS: Ophthalmological screening of asymptomatic HIV
      patients should focus on cytomegalovirus (CMV)-retinitis because early diagnosis
      of this common blinding disease improves the visual outcome. 85 of 215 HIV
      infected patients had a CD4+ count less than 50 cells/microliters 25% of these
      patients developed CMV-retinitis (21/85). The risk for CMV-retinitis rose to 38%
      (13/34) when the low CD4+ count was accompanied by CMV-uria. The proportion of
      patients with CMV-retinitis did not increase when HIV-retinopathy had been
      diagnosed earlier (12/48 = 25%). CMV-serology and CDC-classification were not
      helpful in screening for CMV-retinitis. CONCLUSIONS: We recommend the following
      ophthalmological screening scheme for HIV-patients without ocular symptoms: (1)
      patients with a CD4+ count < 100 cells/microliters should be checked every third
      month and (2) those with a CD4+ count < 50 cells/microliters and CMV-uria every
      sixth week.

PMID- 8992088
TI  - [Fundus oriented microperimetry with the scanning laser ophthalmoscope in age
      induced macular degeneration].
AB  - The indication of laser therapy of subretinal neovascularization is based on the
      visual acuity and the localization and extension of subretinal membranes.
      However, laser therapy based on these guide-lines, repeatedly leads to
      disappointing results as functional effects of neovascularizations on the central
      visual field and fixation are not considered. With fundus-controlled scanning
      laser microperimetry we examined light sensitivity and fixation in areas of
      subretinal neovascularization of 33 patients suffering from beginning (n = 8),
      advanced (n = 17) or hemorrhagic (n = 8) neovascularization in age-related
      macular degeneration. 14 out of 17 patients with signs of advanced and all
      patients with hemorrhagic neovascularization had absolute scotoma in the affected
      area. In each of the patients suffering from beginning neovascularization we
      found relative scotomas and preserved central fixation, even in subfoveal
      membrane localization. The role of scanning laser microperimetry in the
      indication of laser therapy in age-related macular degeneration is discussed.

PMID- 8992087
TI  - [Retinal vessels before and after photocoagulation in diabetic retinopathy.
      Determining the diameter using digitized color fundus slides].
AB  - BACKGROUND: Retinal vessel diameter is an important parameter in blood flow
      analysis. Despite modern digital image technology, most clinical studies
      investigate diameters subjectively using projected fundus slides or negatives. In
      the present study we used a technique to examine vessel diameters by digital
      image analysis of color fundus slides. We investigated in a retrospective manner
      diameter changes in twenty diabetic patients before and after panretinal laser
      coagulation. MATERIAL AND METHODS: Color fundus slides were digitized by a new
      high resolution scanning device. The resulting images consisted in three channels
      (red, green, blue). Since vessel contrast was the highest in the green channel,
      we assessed grey value profiles perpendicular to the vessels in the green
      channel. Diameters were measured at the half-height of the profile. RESULTS:
      After panretinal laser coagulation, average venous diameter was decreased,
      whereas arterial diameter remained unchanged. There was no significant relation
      between the diameter change and the number of laser burns or the presence of
      neovascularization. CONCLUSIONS: Splitting digitized images into color planes
      enables objective measurements of retinal diameters in conventional color slides.

PMID- 8992089
TI  - [Clinical study of the effectiveness of a dexpanthenol containing artificial
      tears solution (Siccaprotect) in treatment of dry eyes].
AB  - PURPOSE: In this controlled, randomized, double-masked study the effect of
      dexpanthenol-containing artificial tears (Siccaprotect) on patients with dry eyes
      was examined. PATIENTS AND METHODS: 50 patients applied either dexpanthenol
      containing artificial tears (Siccaprotect) or the identical, but free of
      dexpanthenol, eye drops five times daily into the conjunctival sac. No other
      ophthalmics were administered. The corneal epithelial permeability was measured
      by fluorophotometry and Schirmer-Test, Rose Bengal staining, tear film break-up
      time and the patients' subjective complaints were determined before and after 6
      weeks of treatment. RESULTS: The dexpanthenol-containing artificial tears
      (Siccaprotect) improved disturbances of the corneal epithelial permeability
      significantly in comparison to the dexpanthenol-free eyes drops. The other
      parameters didn't show relevant differences. CONCLUSION: These data suggest that,
      in dry eyes, treatment with dexpanthenol-containing eye drops leads to a
      favorable and comparing with dexpanthenol-free eye drops superior improvement in
      disturbances of corneal epithelium permeability.

PMID- 8992090
TI  - [A clinical comparative study of tyndallometry using 2 laser flare meters].
AB  - BACKGROUND: The laser flare meter FM-500 (Kowa, diode laser, 670 nm) is a
      simplified version of the laser flare-cell meter FC-1000 (Kowa, He-Ne laser,
      632.8 nm). the aim of this study was to compare flare measurements of the laser
      flare meter FC-500 with the established laser flare-cell meter FC-1000 and to
      determine the reproducibility of both instruments in vivo. PATIENTS AND METHODS:
      Ten eyes of 10 normal subjects (mean age 32.2 +/- 8.0 y) and 21 eyes of 21
      patients (mean age 36.7 +/- 17.2 y) with various forms of uveitis were included
      in the study. Aqueous flare was quantified using the laser flare-cell meter FC
      1000 and the laser flare meter FM-500 by one examiner under comparable
      conditions. The selection of eyes as well as the order of the examinations were
      done in a randomized fashion. Measurements with both instruments were repeated
      the following day in normal eyes. Statistical analysis was done using linear
      regression analysis, intraclass correlation and U-test. RESULTS: Flare values
      (photon counts/ms) did not differ significantly between the instruments either
      for normal eyes (3.3 +/- 0.4 vs 3.5 +/- 0.6) or for eyes with uveitis (16.2 +/-
      9.0 vs 16.4 +/- 8.7). A high correlation of flare counts between both instruments
      was observed in normal eyes (r = 0.73, p < 0.001) and a very high correlation in
      eyes (R = 0.99, p < 0.0001) with mildly to moderately increased counts (< 50
      photon counts/ms). Differences between flare values of both instruments were 
      0.17 +/- 0.4, range -0.8 +/- 0.6 in the normal eyes and -0.23 +/- 1.38, range 
      3.1 +/- 3.4 in the patients with mildly to moderately increased flare counts.
      However, flare counts differed for very high aqueous flare in one patient with
      acute fibrinous iridocyclitis with the FM-500 indicating higher values. The
      intraclass correlation coefficients were 0.70 for the FC-1000 and 0.76 for the FM
      500 in normal eyes and 0.99 for both instruments in eyes with uveitis.
      CONCLUSIONS: In eyes without or with mild to moderate breakdown of the blood
      aqueous barrier, the two instruments give comparable results. However,
      measurements may differ in eyes with high flare readings.

PMID- 8992091
TI  - [Acceptance of progressive lenses].
AB  - BACKGROUND: The wearing of progressive lens poses a problem to two kinds of
      patients: those who are practically emmetropic and use reading glasses only, and
      ametropic patients whose eyes have been corrected for years with bifocals. The
      wearing of progressive lenses is generally not recommended for those presbyopes.
      METHODS: A group of individuals (n = 50) underwent refraction, and their addition
      was adjusted to their work and their age (44-72 years). They were then divided
      into two groups, one of which (n = 25) was equipped with bifocals (Telarc,
      Essilor) and the other (n = 25) with progressive lenses (Varilux Comfort,
      Essilor). After four weeks, the types of glasses were exchanged. After a further
      four weeks, each group used the original pair of glasses for another week. At the
      end of this phase, each of the test subjects was asked his opinion in favour of
      one or the other types of glasses. At each change of glasses, factors such as
      duration of the adaptation period, assessment of sight, general impression and
      time of use were recorded. RESULTS: At the determination of refraction much
      attention must be given to mildly astigmatic patients in order to optimise the
      prescription of progressive lenses. Progressive lenses were just as well
      tolerated by the group of convinced bifocal wearers, even though the
      familiarisation period took up to two weeks, especially for the older patients.
      Once the progressive lenses had been accepted, bifocals were generally abandoned
      for good. This is mainly due to the quality of the progressive lenses, which
      favour precise vision even in intermediate zones. For most of the individuals who
      were previously fitted with reading glasses only, the demarcation line between
      the distant and near parts of the bifocal lens pose major problems. Whereas
      progressive lenses were accepted as readily as in the group previously fitted
      with bifocals, about 40% of the total individuals tested refused bifocal lenses.
      CONCLUSION: In all, 96% of the participants considered progressive lenses good or
      very good. All recognised that progressive lenses represent the most aesthetic
      solution. However, in certain cases bifocal lenses together with progressive
      lenses remain interesting. For patients who were previously accustomed to reading
      glasses only, the duration of use of glasses with progressive lenses rose from
      40% to 60% of the working day.

PMID- 8992092
TI  - [Kohlschutter syndrome--an example of a rare progressive neuroectodermal disease.
      Case report and review of the literature].
AB  - Kohlschutter's syndrome is a combination of amelogenesis imperfecta, progressive
      mental retardation and epileptic seizures. We report on a patient with typical
      signs of this syndrome. Beneath severe enamal defects of teeth, the patient has
      been suffering from progressive mental and motoric retardation from the age of
      six months. Although there is pathologic activity in EEG, seizures have not yet
      appeared. MRT shows distinct signs of cerebral atrophy. Apart from this patient
      15 patients in 4 families have been reported up to now in literature. The article
      compares diagnostic results in this case with those reported in literature.

PMID- 8992093
TI  - [Cerebral palsy (I)--an analysis of the concept].
AB  - A review of the literature reveals that, until now, there is no clear and
      commonly accepted definition of the term 'cerebral palsy' (CP). The term is used
      for different kinds of symptomatology and pathogenesis which are actually quite
      heterogeneous. A detailed analysis of the criteria for defining indicates that a
      clear definition is impossible. The contradictions inherent in this term arise
      form the fact that its usage covers a wide range of clinical and pathogenetic
      essentials which are often incompatible. The term 'CP' is valuable only from the
      administrative and therapeutic point of view. But as it is often wrongly
      interpreted as a diagnosis it should no longer be used in medical and scientific
      communication.

PMID- 8992094
TI  - [Cerebral palsy (II)--clinical symptoms and etiopathogenesis].
AB  - In our first report we analysed the criteria for defining the term 'cerebral
      palsy'. In this paper we deal with the problems arising from this terminology and
      exemplify this by presenting some case reports. It will be shown that the usage
      of the term 'CP'--misunderstood as a diagnosis--often hinders the correct
      analysis of the underlying pathogenesis and aetiology. Thus genetic, therapeutic
      and forensic implications of the underlying disease or lesion are easily over
      looked.

PMID- 8992095
TI  - [Sleep evaluation in infancy, early childhood and childhood].
AB  - There is no common strategy for the determination of sleep stages in the
      childhood. In the first year of life, the differentiation in active and quiet
      sleep has been established. But there are several opinions about necessary
      parameters for the characterization of sleep states in this period of life.
      Therefore, the results of these evaluations are quite different. Our presented
      concept of sleep staging reflects neurophysiological, vegetative as well as
      behavioral parameters. The concept divides the sleep into light sleep, deep sleep
      and REM-periods. The determination of sleep states is possible by this concept
      both in infants and in children of different age, because it considers
      developmental changes of used physiological criteria.

PMID- 8992096
TI  - [Early auditory evoked potentials in children with language development
      disorders].
AB  - One of the prerequisites for normal language development is a highly sensitive
      auditory perception. An auditory perception deficit is therefore likely to affect
      the normal course of language acquisition. To test this hypothesis, we studied
      the BAEPs in 25 preschool boys with an expressive developmental language disorder
      and 12 boys with a history of stuttering. These children had no hearing
      disorders. Comparisons with the control group (49 neurologically healthy male
      subjects with normal hearing) revealed a statistically significant delay of waves
      III, IV and V in the language impaired subjects, whereas no significant
      differences were detected in the group of stutterers. Our findings suggest that a
      delayed or altered conduction of acoustic stimuli is important to the
      pathogenesis of developmental language disorders.

PMID- 8992097
TI  - [Munster Heidelberg Abilities Scale--a measuring instrument for global comparison
      of illness sequelae].
AB  - An instrument to measure quality of life in multicentric pediatric studies in
      German language was missing yet. The FMH measures the capability for daily life
      actions with 56 items like "can walk without aids" or "earns money". It was
      normalized with 971 persons (45.5% female) aging between 0 and 102 years
      resulting in age-dependent percentiles. The retest-reliability-coefficient is
      0.99. The validity was tested in 10 brain tumor patients: there was a good
      agreement with the IQ (r = 0.7) and with a semiquantitative assessment by a
      physician (p < 0.001).

PMID- 8992099
TI  - [Immunologic findings in HIV infected children with bacterial infections].
AB  - BACKGROUND: Bacterial infections are a major cause of illness in HIV-infected
      children. HIV-infected children with severe dysfunction of cellular and humoral
      immunity are particularly vulnerable. METHODS AND PATIENTS: We conducted a
      retrospective study to analyse the incidence and spectrum of bacterial infections
      in HIV-infected children compared to HIV-exposed but not infected controls
      related to their immunological status. Data collected during 1985 to May 1993
      were evaluated considering 333 HIV-infected and 81 controls. RESULTS: During
      observation time 359 episodes (29% of the visits) of purulent rhinitis were
      diagnosed in HIV-infected children compared to the controls (53 episodes/8%); p =
      0.0001. Comparable results were seen in otitis media. 178 episodes/14% were found
      in HIV-infected children and 66 episodes/10% in the controls (p = 0.001). 53
      episodes/5% of bacterial pneumonia were represented in HIV-infected versus 11
      episodes/2% in controls (p = 0.001). The increase of lymphocyte immune defect
      correlated to an increase of bacterial infections. This alterations were
      particularly observed in HIV-infected children with bacterial pneumonia. Severe
      dysfunction of cellular immunity was found in children with recurrent pneumonia
      compared to children with only one episode of bacterial pneumonia. The
      proliferate response of peripheral blood lymphocyte to pokeweed mitogen (13,351
      cpm versus 3080 cpm); p = 0.009 and Concanavalin A (12,607 cpm versus 2470 cpm);
      p = 0.01 was significantly reduced in both groups, although the defect was much
      more pronounced in the group with the recurrent pneumonia. CONCLUSIONS: Our
      observations results showed that bacterial respiratory tract infections occurred
      significantly more frequently in HIV-infected children compared to an age related
      control group. Not only the occurrence of opportunity infections but also severe
      bacterial infections especially recurrent pneumonia are associated with a defect
      in cell-mediated immunity.

PMID- 8992098
TI  - [Nervous system manifestations in HIV infected children].
AB  - In 34 perinatally HIV infected children time of manifestation, type and
      treatability of neurologic disorders were investigated for a period of 7 years
      (1987-1994). Neurological investigations were done every 6 months; EEG and MRI/CT
      were examined initially in the asymptomatic stage and were repeated when
      neurologic Symptoms occurred. Zidovudine therapy was started after onset of
      symptoms, dosage was raised, when treatment with Zidovudine had already begun
      (600-720 mg/m2/day). Various neurological manifestations were seen in 4 of 12
      patients in stage B (33%) and in 11 of 14 children in AIDS (80%). 7 of the 14
      AIDS-patients (50%) developed a subacute progressive course or progressive
      plateau course and 4 of 14 (30%) a static course of encephalopathy. Pathological
      changes in EEG were seen in 54% of investigated patients with neurological
      deficits. Neuroimaging revealed pathological findings in all symptomatic
      subjects, 6 of 11 patients in AIDS (55%) has a severe general cerebral atrophy
      and multifocal white matter lesions. Zidovudine had a positive temporary effect
      from 6 to 12 months in 5 of 11 treated patients (45%). At present a thorough
      neurological examination is the most sensitive method to detect neurological
      impairment in HIV infected children. In most cases CT/MRI scan provides
      information about the course of the encephalopathy. Antiretroviral therapy has a
      limited benefit, if neurologic symptoms start after the second year of life.

PMID- 8992100
TI  - [5-day therapy of bacterial pharyngitis and tonsillitis with cefixime. Comparison
      with 10 day treatment with penicillin V. Cefixime Study Group].
AB  - 160 children aged 1 to 12 years with clinical diagnosis of bacterial pharyngitis
      and/or tonsillitis were treated either with cefixime ready-to-use-suspension or
      penicillin V in an open, controlled and randomized multicenter study. Before
      treatment a rapid antigen detection test was accomplished and throat swabs were
      taken. After randomization, the children were either treated for 5 days with 8 mg
      cefixime/kg bodyweight ready-to-use suspension once daily or with 20,000 I.U.
      penicillin V/kg bodyweight t.i.d. also administered as suspension. The data of
      151 children could be evaluated for clinically efficacy. In the cefixime-group
      86.7% of the children were cured and 9.3% significantly improved. After initial
      improvement, in one child (1.3%) a relapse occurred and in the two remaining
      children (2.7%) therapy failed. 90.8% of the patients treated with penicillin V
      were cured, 6.6% improved and in one child each a relapse was registered resp.
      therapy failed. Complete microbiological data were available in 137 patients. In
      the cefixime-group in 82.6% of the patients the pathogens were eradicated. The
      elimination rate in the penicillin-group was 88.2%. At the follow-up 3-4 weeks
      after end of treatment 6 relapses were seen in the cefixime-group, and 8 in the
      patients treated with penicillin. Both regimes were safe. Mild to moderate
      adverse events at least possibly related to the study medication were seen in
      only 4 children treated with cefixime and in 5 treated with penicillin. A 5 day
      treatment of bacterial pharyngitis and tonsillitis with cefixime was as effective
      as a ten day treatment with penicillin V.

PMID- 8992101
TI  - [Recommendations for tuberculin testing in childhood for Germany].

PMID- 8992102
TI  - [Septic and other forms of salmonellosis].

PMID- 8992103
TI  - [Profiles of serological markers of HBV-infection in acute hepatitis B].
AB  - The authors demonstrate that severe and fulminant forms of acute hepatitis B
      (AHB) are associated with low concentrations of HBsAg and anti HBs in peripheral
      blood. In the majority of cyclic AHB cases HBeAg is registered in the serum for 2
      3 weeks, whereas in more severe course of AHB its indication is shorter, with
      occasional occurrence of serological window. The more severe and longer was AHB
      course the lower was concentration of HBsAg in peripheral blood. The assessment
      of the complete profile of serological markers of HBV infection and HBsAg
      concentration in the serum in the course of the disease will promote more
      effective diagnosis of the disease pattern and outcome.

PMID- 8992104
TI  - [Hemostasis and pathogenetic therapy of unstable angina pectoris].
AB  - Peculiar features of clinical course and outcomes of unstable angina are outlined
      with respect to severity of disturbances of interrelated coagulation,
      fibrinolytic and kallikrein systems, variants of DIC-syndrome run and
      antithrombotic treatment. The authors also give the description of laboratory
      methods of control over adequacy of anticoagulant and thrombolytic therapy and
      the analysis of effectiveness of transcutaneous transluminal coronary angioplasty
      and its action on factor Hageman system. The highest response was obtained in the
      group of patients on combined prolonged heparic treatment.

PMID- 8992105
TI  - [Prevalence of early repolarization syndrome].
AB  - Early repolarization of the heart ventricles occurs in population over 13 years
      old rather evenly. In children it is encountered significantly more frequently
      than in adults, in males 2 times more often than in females, in inpatients,
      especially with gastrointestinal and nervous diseases, more frequently than in
      population. In patients with organic cardiovascular disorders the syndrome occurs
      less frequently.

PMID- 8992106
TI  - [Prolonged normovolemic hemodilution in therapy of patients with obliterating
      endarteritis of lower limb vessels].
AB  - The response to prolonged normovolemic hemodilution in 101 patients with
      obliterating endarteritis of the legs manifested as pain relief in 84.2%,
      complete or partial healing of trophic ulcers in 82.9 and 17% of cases,
      respectively, remission from stage III to stage II, from stage II to stage I in
      47% and 37.3% of patients, respectively. There was also less frequent occurrence
      of postoperative specific and nonspecific complications, of high-traumatic
      amputations.

PMID- 8992107
TI  - [Immunogenetic aspects of pathogenesis, prognosis and treatment of the main forms
      of chronic pancreatitis].
AB  - Immunogenetic examination comprising determination of erythrocyte antigens (ABO
      systems and resus-factor) and leukocytes (HLA system) using hemagglutination and
      compliment-dependent cytotoxicity, respectively, was performed for 138 patients
      with chronic recurrent pancreatitis, 52 patients with chronic pancreatitis and
      456 healthy subjects. Analysis of relations between the above antigens, the
      disease risk, clinical and laboratory parameters, readings of ultrasound
      histogram and the efficacy of treatment helped discover not only provoking and
      protecting genes, but also some pathogenetic mechanisms involved in genetic
      predisposition. These findings may be used in the choice of treatment policy and
      to upgrade the significance of prognosis of principal forms of chronic
      pancreatitis.

PMID- 8992108
TI  - [Factors predicting chronic renal failure in membranoproliferative
      glomerulonephritis].
AB  - Multivariate analysis of overall clinicomorphological signs in 58 patients with
      membranoproliferative glomerulonphiritis (MPG) and investigation of functional
      survival outlined independent prognostic factors valuable for predicting
      progression of chronic renal failure. These were: exacerbation > 1 time in 3
      years, secondary hypertension, concentration of serum creatinine > 0.13 mmol/l,
      marked tubulointerstitial changes, global glomerular sclerosis > 30%, 24-hour
      proteinuria > 8 g.

PMID- 8992109
TI  - [Pre- and postsurgical treatment condition of cardiovascular and endocrine
      systems in patients with endogenic hypercorticism ].

PMID- 8992110
TI  - [Etiological non-homogeneity of subacute thyroiditis].

PMID- 8992111
TI  - [Adaptation of regulatory physiological systems in surgical treatment of patients
      with bronchial asthma].
AB  - Selective denervation of the lung (SDL) has been conducted in 389 patients with
      bronchial asthma. This operation stimulates function of Tg-suppressors, enhances
      the activity of blocked adrenergic structures and glucocorticoid supply,
      attenuates adrenal and extraadrenal insufficiency. SDL is thought
      pathogenetically validated in bronchial asthma with deficient suppression,
      generalized adrenodeficiency, combined glucocorticoid insufficiency.

PMID- 8992112
TI  - [Comparative estimation of biocontrolled endoscopic and transcutaneous laser
      therapy of ulcer].

PMID- 8992113
TI  - [Urgent problems of tuberculosis].

PMID- 8992114
TI  - [Diagnostic and prognostic significance of membranodestructive process in
      mechanic jaundice and phlegmonous cholecystitis in patients with diabetes
      mellitus].
AB  - Investigations performed in 96 patients with diabetes mellitus and acute biliary
      pathology (phlegmonous cholecystitis, mechanic jaundice) have found the
      relationships between plasma lypoperoxidation, degree of hepatodepression and
      kind of inflammation in the gall bladder. The level of glycemia and degree of
      transferasemia (cytolytic syndrome) are not reliable criteria of acute hepatic
      insufficiency and pyoinflammatory process in the biliary tracts. The choice of
      the complex of membrane-stabilizing drugs should be based on the severity and
      pattern of endotoxicosis.

PMID- 8992115
TI  - [Kallikrein-kinin indices and biological composition of exhaled condensate in
      acute bronchitis patients with varying disease course].
AB  - Parameters of blood kallikrein-kinin system (KKS) and biochemical composition of
      humor condensated from the exhaled air have been evaluated in 87 patients with
      acute bronchitis (36 cases with lingering course and 31 with recurrent). The
      progression of acute bronchitis is associated with elevated blood concentrations
      of acute-phase proteins, KKS activation in the blood and high serotonin and
      lactic acid content in the humor condensated from the exhaled air. Lingering and
      recurrent course of the disease are characterized by more pronounced reduction in
      inhibitory activity of kallikrein, in activity of angiotensin-converting enzyme
      and emergence of noradrenalin in high concentration.

PMID- 8992116
TI  - [Parasitic invasions and bronchial obstruction].
AB  - The course and outcomes of bronchial obstruction were reviewed for clonorchiasis,
      metagonimosis, lambliasis. Bronchial obstruction is shown to run more aggressive
      course in Trematoda infestation with further transformation into bronchial asthma
      despite dehelminthization. In lambliasis current antiparasitic therapy is able to
      abolish the obstruction. In combination of lambliasis with bronchial asthma it is
      feasible to achieve a persistent remission of bronchial asthma.

PMID- 8992117
TI  - [Antibodies to collagen type I and fibronectin in patients with scleroderma
      systemic ].
AB  - Antibodies to collagen type I, total and immunoactive plasmic fibronectin were
      measured in 39 patients with scleroderma systematica using solid-phase enzyme
      immunoassay. It was found that growing activity of the disease was associated
      with an increase in the titer of antibodies to collagen type I and a decrease in
      the level of immunoactive fibronectin. With enhancement of the process
      generalization, the titer to the antibodies also rose. Total fibronectin in
      patients with scleroderma systematica and normal subjects was the same.

PMID- 8992118
TI  - [Functional activity of the liver and lipopolysaccharide-positive neutrophils of
      peripheral blood in patients with acute dysentery].
AB  - Acute phase proteins (albumin, prealbumin, transferrin, haptoglobin) and the
      results of spontaneous and load tests of lipopolysaccharide-positive neutrophils
      (LPS-PN) in peripheral blood were studied in the course of acute colitic
      dysentery in 34 patients. It is shown that at the height of the disease there was
      a fall in the levels of albumin, prealbumin, transferrin while haptoglobin levels
      were elevated. More persistent and pronounced changes were noted in patients with
      severe course of acute dysentery. In acute period of the disease there were low
      values of spontaneous and load LPS-PN tests depending on the disease severity.
      None of the above parameters returned to control levels within 5-6 days after the
      start of the treatment.

PMID- 8992119
TI  - [Tropical malaria pattern in Russians living in the Republic of Guinea].
AB  - Tropical malaria in 188 Russians who have fallen ill in the Republic of Guinea
      was characterized by an acute onset, high irregular 6-day fever, intoxication,
      hepatosplenomegaly, moderate of severe forms, high incidence of recurrences.
      Combination of kinimax with fansidar seemed more effective than routine treatment
      with chlorochin.

PMID- 8992120
TI  - [Clinicoimmunological effects of piracetam and aevit in the course of duodenal
      ulcer patients' therapy].

PMID- 8992121
TI  - [Automatic implantable cardioverter-defibrillators in treating life-threatening
      ventricular tachyarrhythmias].

PMID- 8992122
TI  - [An unusual course of carcinoid tumor].

PMID- 8992123
TI  - [Fever of unknown origin].

PMID- 8992124
TI  - [Alcohol and bronchial asthma].

PMID- 8992125
TI  - [Herpetic infection].

PMID- 8992126
TI  - [Pathogenesis and diagnosis of macrofocal myocardial lesions in dilated
      cardiomyopathy].

PMID- 8992127
TI  - Influence of the age and sex on respiratory burst of human monocytes.
AB  - The respiratory burst reaction has been studied in monocytes from men and women
      of different age. Phorbol myristate acetate (PMA) was used to stimulate NADPH
      oxidase. Superoxide anion production was found to be dependent on age and sex (it
      decreased 45% in men and 70% in women during aging).

PMID- 8992128
TI  - [Drug consumption in diabetes mellitus (V). Pharmacoeconomics and the acceptance
      of the hospital changeover to insulin U100. Group for the Study of Diabetes in
      Tarragona].
AB  - BACKGROUND: The U100 insulin (100 units [U]/ml) in only used in a minority of
      Spanish hospitals and is not ordinarily evaluated. To study the convenience of
      converting from U40 (40 U/ml) to U100 insulin in a first level hospital, the
      procedure, costs and professional acceptance were analyzed after one year of
      experience. SUBJECTS AND METHODS: The chronology and the transfer method are
      described making an interannual pharmacoeconomical comparison of costs U40/U100
      based on insulin intake and injection material. The primary source of information
      was the computerized base of admission, pharmacy and supply. The secondary source
      included the obligatory registries of daily medicine sheets. Nursing staff
      acceptance of the new system (preloaded U100 syringes) was analyzed with a
      predesigned quantitative scale questionnaire. RESULTS: In the U40 phase, 69,600 U
      and 8,260 syringes were used to satisfy 136 diabetics at a mean prescription of
      21 U/day for 10.9 days. In the U100 phase, 92,100 U and 1,682 syringes were used
      for 132 admissions with a mean dose of 20 U during 8.6 days. The insulin
      prescribed and injected was 45.5% and 24.7%, respectively with the consumption of
      non injected insulin in the center being 20.8%. On taking only the fraction
      injected into consideration, the mean daily cost per complete treatment was lower
      in U100 (116/84 and 1,368/809 pesetas; p < 0.0001) representing 0.53% (U40) and
      0.36% (U100) of hospital stay costs. The total cost increased by 44
      ptas./patient/day during the first year of conversion. Each section of the 67
      questionnaires evaluated scored from 4 (greatest acceptance) to 20 (lowest
      acceptance). The general mean was 6.8 +/- 1.6 with no significant differences
      between the section of management/manipulation of U100 devices (6.7 +/- 2.1),
      learning and protocol (7.3 +/- 2.6) and patient education (6.5 +/- 1.8; p = 0.07,
      NS). CONCLUSIONS: Current hospital conversion to U100 insulin requires the use of
      mechanized injection systems which represent a slight extra cost of scarce social
      relevance and are greatly accepted by users if adequate transfer procedures are
      applied.

PMID- 8992129
TI  - [The treatment of chronic hepatitis C with interferon in patients infected with
      the human immunodeficiency virus. The Spanish Group for the Study of Viral
      Hepatitis in HIV+ Patients].
AB  - BACKGROUND: Alfa-interferon (aIFN) is widely recommended for the treatment of
      chronic hepatitis C (CHC). Hepatitis C virus (HCV) infection is very common in
      injecting drug users (IDUs), which in Spain represent the large number of HIV
      infected persons. Interaction between human immunodeficiency virus (HIV) and HCV
      in coinfected patients might accelerate the clinical course of HCV-associated
      liver disease. The efficacy and safety of aIFN therapy in HIV-infected patients
      with CHC is not well known. PATIENTS AND METHODS: In a multicenter, prospective,
      open, non randomized and partially controlled study, we compared the efficacy and
      safety of aIFN therapy in 119 patients with CHC, of whom 90 were HIV-positive and
      29 HIV-negative. Interferon was started at 5 mega U tiw for 3 months, followed in
      responders by 3 megaU tiw for additional 9 months. RESULTS: One hundred seven
      patients completed the study. A normalization of the aminotransferase values at
      the end of treatment (complete response, CR) was observed in 26/80 (32.5%) HIV
      positive and 10/27 (37.0%) HIV-negative individuals (p = 0.666). Relapses at 12
      months of stopping aIFN were seen in 30.8% of HIV-positive subjects and 12.5% of
      HIV-negatives (p = 0.403). Side effects were uncommon and did not have severity;
      only one patient required to stop the medication. However, 3 HIV-positive
      subjects treated with aIFN (3.5% of them) showed an irreversible fall of CD4+ T
      cells below half the baseline values. CONCLUSION: HIV-infected patients with CHC
      seems to respond to aIFN with a similar rate than HIV-negatives. Moreover, the
      drug is similarly well tolerated in both groups of patients, although a fall of
      CD4+ T-cells is an unusual side effect of particular relevance observed in HIV
      infected patients.

PMID- 8992131
TI  - [The changeover to insulin U100. Clinical and pharmacoeconomic suggestions].

PMID- 8992130
TI  - [The prevalence of markers for the hepatitis A and B viruses in the population of
      Gijon between 6 and 25 years old].
AB  - BACKGROUND: The aim of this study was to know the prevalence of previous
      infection markers for hepatitis A and B viruses in a pediatric-juvenile
      population from Gijon, Spain. PATIENTS AND METHODS: A representative (according
      to the census) transversal randomized sample of a population from 6 to 25 years
      in age from Gijon, Spain, was included in the study analyzing demographic,
      epidemiologic and clinical variables, liver tests, anti-HAV IgG and anti-HBc.
      RESULTS: Of the 630 individuals selected a demographic error was detected in 28
      (4.4%) and 453 subjects were studied (71.9%) in whom the anti-HAV IgG was
      positive in 37 cases (8.75% of prevalence adjusted for age), with 4.4% (12/271)
      (CI 95% 2.3%-7.6%) for the younger cases and 13.7% (25/182) (CI 95% 9.1%-19.6%)
      in the group ranging from 18 to 25 years in age (p < 0.001). No anti-HAV IgG
      positive case was detected in the population under the age of 10 years. Among the
      young adults the prevalence of anti-HAV IgG positive cases was higher in those
      born in the south of Spain (2/6, 33.3%) (CI 95% 4.3%-77.7%) with respect to those
      from the northern regions of Spain (9/259, 3.5%) (CI 95% 1.6%-6.4%). (p = 0.02).
      With respect to HBV markers, of the 433 unvaccinated cases, 6 (1.4%) presented
      markers of past infection and 2 (0.46%) HBsAg positivity. Both had normal serum
      ALT without viral replication. Six cases of hypertransaminasemia levels (1.3%)
      were detected all being related with obesity or alcoholism. All the cases with
      previous acute clinical hepatitis were found to be anti-HAV IgG positive and anti
      HBc negative. CONCLUSIONS: The current prevalence of anti-HAV IgG in the
      population from 6 to 25 years from Gijon, Spain is very low and given the high
      degree of susceptibility (86%) for HAV infection in the young adult population
      (18-25 years) the implementation of vaccination programs is recommended even
      without previous serologic screening. The low prevalence of anti-Hbc would also
      undervalue its use as prevaccination screening against HB in this geographical
      area.

PMID- 8992132
TI  - [Pulmonary thromboendarterectomy in a patient with primary antiphospholipid
      syndrome].
AB  - Pulmonary arterial hypertension (PAH) is an infrequent manifestation of the
      primary antiphospholipid syndrome (PAPS). It may appear due to different
      mechanisms although the most common cause is recurrent pulmonary embolisms. In
      some cases the thrombi do not dissolve and organize to form fibrous masses which
      occlude the pulmonary veins giving place to chronic thromboembolic pulmonary
      hypertension. When the thrombi are located in the proximal arteries,
      thromboendarterectomy may be curative. The first case of a patient with PAPS
      diagnosed with PAH secondary to chronic thrombosis of the proximal pulmonary
      arteries, in whom a successful pulmonary thromboendarterectomy was performed is
      herein reported.

PMID- 8992133
TI  - [Cuba's epidemic of neuropathy: 1991, 1994].

PMID- 8992134
TI  - [The therapeutic applications of octreotide].

PMID- 8992135
TI  - [The consumption of alcoholic drinks in Spain in the period of 1940-1987].

PMID- 8992136
TI  - [The reactive airways dysfunction syndrome induced by glue].

PMID- 8992137
TI  - [The functional gammagraphic study of adrenal tumors found by chance].

PMID- 8992138
TI  - [Relapsing focal myositis].

PMID- 8992139
TI  - [The hospital library and Internet].

PMID- 8992140
TI  - [Study from the County Council shows: private practices are more efficient than
      public ones].

PMID- 8992142
TI  - [The government doesn't care about negotiation on tariffs].

PMID- 8992141
TI  - [Occupational environment in primary health care is getting worse. The most
      significance cause is too large number of patients].

PMID- 8992143
TI  - [Quality of primary health care provided by municipalities respective county
      councils should be equal].

PMID- 8992144
TI  - [A fairy tale and truth about jobs in the Persian Gulf].

PMID- 8992145
TI  - [How does a Swedish physician "survive" when working in the Middle East?].

PMID- 8992146
TI  - [Medical students caught in mass production. Conceited and deflated... at the
      same time].

PMID- 8992147
TI  - ["Perform autopsies, but avoid to confirm the cause of death!" What is the point
      of the new autopsy law?].

PMID- 8992148
TI  - [Informed consent--an exception or a rule?].

PMID- 8992149
TI  - [Cost savings strike both the patients and the personnel].

PMID- 8992150
TI  - [Breast feeding is threatened by a recommendation. Society of Pediatricians,
      Sweden].

PMID- 8992151
TI  - [Don't be ashamed of your maternity department anymore, do something to improve
      it!].

PMID- 8992152
TI  - [Meaningless with an expensive yeast preparation in diarrhea].

PMID- 8992153
TI  - [Can treatment wait until gastroscopy is performed?].

PMID- 8992154
TI  - [Triplet pregnancy is met with pleasure].

PMID- 8992155
TI  - [Exotic snakes may strike even here!].

PMID- 8992157
TI  - [Venous catheterization can cause infusion thrombophlebitis. Study of the
      literature on its causes and occurrence].

PMID- 8992156
TI  - [Gluten. Changed recommendations for infant care. Society of Pediatricians,
      Sweden].

PMID- 8992158
TI  - [Is psychotherapy in depression efficient? Physician-patient relations are
      significant for therapeutic results].

PMID- 8992159
TI  - [Tropical snakes as a risk of accidents even in Sweden. Four cases from the
      Norrbotten].

PMID- 8992160
TI  - [A survey of registered traumas at the Mora hospital. Hospital size does not
      determine achievement].

PMID- 8992161
TI  - [Award for the research on blood coagulation. (Bjorn Dahlback)].

PMID- 8992162
TI  - [Deficient follow-up of surgically treated fractures of the foot joint. Tendency
      towards fewer check-ups because of cost savings].

PMID- 8992163
TI  - [Compensation after delayed diagnosis of breast cancer. Passiveness and uncertain
      routines caused damage].

PMID- 8992164
TI  - [Clear distribution of responsibility is needed in teaching a surgical
      technique].

PMID- 8992165
TI  - [Neglected notification of communicable disease].

PMID- 8992166
TI  - [A letter from a convalescent].

PMID- 8992167
TI  - [A holistic perspective in a new Swedish study. Connection between H pylori and
      cancer].

PMID- 8992168
TI  - [Swedish registries are of favour for epidemiological research].

PMID- 8992169
TI  - [28-year follow up of smoking habits of Swedish physicians. Reduced number of
      smokers but increased number of snuff-users].

PMID- 8992170
TI  - [Schizophrenia--a concept of duality].

PMID- 8992171
TI  - [Blood reinfusion in orthopedic surgery in Sweden. The most common method is
      wound reinfusion].

PMID- 8992172
TI  - [More effective resuscitation in a special ambulance. Increased survival after
      cardiac arrest in Gothenburg].

PMID- 8992173
TI  - [Unjustified fear. Rare frequency of drug prescription by district nurses].

PMID- 8992174
TI  - Healing the Children: medical missions.
AB  - In 1993, I started documenting medical missions organised by the American-based,
      non-profit organisation Healing the Children (HTC). With 14 chapters in 21
      states, HTC has helped tens of thousands of children worldwide since it was
      founded in 1979. The organisation arranges specialised medical treatment and
      surgical care for children whose families cannot afford it or whose communities
      do not offer it. HTC relies entirely on volunteers. In 1995, the northeast
      chapter of HTC alone provided more than $7.5 million in services to about 2300
      children. HTC also provides treatment and assistance to disadvantaged children in
      US communities, arranges special care in the USA for children from nearly 60
      countries, and recruits organisations to provide supplies and refurbished
      equipment to hospitals in underdeveloped countries. In October, 1994, I travelled
      with an HTC team of over 50 medical personnel on a cardiac trip to Guatemala
      City. More recently, in April, 1996, I documented a team of 11 who travelled to
      Cochahamba, Bolivia, to carry out soft tissue surgery.

PMID- 8992175
TI  - Surgery moves into the third dimension [new].

PMID- 8992176
TI  - [Control of the stability of conditions in photochemical processing of
      radiographic films. Ministry of Health and Medical Industry of the Russian
      Federation].
AB  - To develop general requirements for evaluating and controlling the operating
      parameters of X-ray equipment at the units (rooms) of X-ray diagnosis, the
      International Electric Engineering Commission (IEEC) has published a number of
      guidelines concerning control methods. Of the most importance are the IEEC
      Guidelines 1223-2-1-93, 1223-2-2-93, and 1223-2-3-93 for controlling the premises
      and technical equipment of X-ray photo laboratories, which have translated into
      Russian, adjusted to our conditions, approved by the Ministry of Health and
      Medical Industry of the Russian Federation and published as 3 guidelines P 42-502
      95, P 42-503-95, P 42-504-95 to be introduced on August 1, 1995. The publication
      totally reflects the main points of the guidelines, which enables them to be used
      under practical conditions.

PMID- 8992177
TI  - [General guidelines for evaluating and controlling the operating parameters of x
      ray diagnostic equipment. Ministry of Health and Medical Industry of the Russian
      Federation].
AB  - The International Electric Engineering Commission (IEEC) has published several
      guidelines for evaluating and controlling the operating parameters of X-ray
      diagnostic equipment at the units (rooms) of X-ray diagnosis. The first of these
      guidelines (IEEC 1223-1-93) having the subheading "General Requirements" is
      translated into Russian and adjusted to our conditions, approved by the Ministry
      of Health and Medical Industry of the Russian Federation and published as the
      guidelines P 42-501-95 to be introduced on July 1, 1995. The publication reflects
      the main contents of the national variant of the document, gives a scheme (an
      algorithm) for controlling the quality of X-ray diagnostic equipment.

PMID- 8992178
TI  - [Measurements in emergency laparoscopic surgery].
AB  - The paper deals with the advantages of the techniques of abdominal surgical
      interventions by using a laparoscope. It suggests that the diagnostic
      feasibilities of laparoscopy should be expanded by inserting the transducers that
      yield reliable data on the status of the viscera.

PMID- 8992179
TI  - [Changes in the reflective capacity of damaged biological tissues in visual
      endoscopy].

PMID- 8992180
TI  - [Comparative hydrodynamic evaluation of variants of the cavopulmonary
      anastomosis].
AB  - An analysis of the range of postoperative complications following cavapulmonary
      anastomosis reveals a number of medical engineering problems in surgery
      techniques. The severity of the surgery due to the nonphysiological rearrangement
      of blood circulation makes it necessary to search for the most optimal types of
      anastomosis in terms of the hemo- and hydrodynamics of circulation. To optimize
      the performance of cavapulmonary anastomosis, namely to define the mutual
      localization and orientation of the implanted anastomoses against the axes of
      inflow and outflow, hemo- and hydrodynamic studies were made by Doppler laser
      anemometry. From the hydrodynamic point of view, the findings indicate the most
      optimal type of cavapulmonary anastomosis-cruciform anastomosis by displacing 0.5
      d from the outflow axis at an angle of 60e5 degrees.

PMID- 8992181
TI  - [Effects of heterogeneity of gas channels on carbon dioxide output of membrane
      oxygenators].
AB  - A relationship between the carbon dioxide output of the oxygenators and the value
      of ventilating gas flow is analyzed. It is shown that a potential inhomogeneity
      of gas channels may result from the lower efficiency of the oxygenators. The
      tests of the MOST oxygenators have indicated that the achieved homogeneity of
      their gas chambers is sufficient for carbon dioxide to be effectively removed.

PMID- 8992182
TI  - [Distribution of current density over the surface of electrodes of an autonomic
      stimulator of the gastrointestinal tract].
AB  - The paper outlines a distributed self-contained gastrointestinal
      electrostimulator model that considers current distribution in the electrolytic
      environment and electrochemical polarization inhomogeneity over the surface of
      cap electrodes. The model is satisfactory in describing the experimental data
      obtained for electrodes made of the stainless steel 12X18H9 in 1% hydrochloric
      acid solution (that mimics gastric acid) and may be useful in evaluating the
      performance of and in optimizing the self-contained electrostimulator with the
      electrodes covered by different materials.

PMID- 8992183
TI  - [Problems of metrological support of medical studies].

PMID- 8992184
TI  - [Inductance transducers for borderline localization of metallic foreign bodies].
AB  - The paper outlines the advantages and disadvantages of a ferroprobe inductance
      transducer used in the borderline localization of a foreign ferromagnetic body.
      To eliminate the ferroprobe transducer-inherent disadvantages, a whirl-current
      inductance transducer has been developed. The transducer localizes a foreign
      nonferromagnetic and ferromagnetic body in its borderline localization in the eye
      and in the whole body.

PMID- 8992185
TI  - [Transducer for pulse diagnostics].
AB  - The paper presents a new transducer for experiments to define parameters of the
      pattern of pulses in Tibetan medical sources. The transducer has a number of
      benefits which successfully measures pulse signals required for computer-aided
      processing.

PMID- 8992186
TI  - [Several aspects of software implementation of a computerized pulse diagnostics
      complex].
AB  - To develop a diagnostic system based on the methods of Tibetan medicine is actual
      due to the extensive, highly informative and well-structuralized database
      accumulated in Tibetan pulse diagnosis. There are several methods for processing
      the signals which may be useful in making a diagnostic catalogue of pulses. Some
      aspects of building software for the function of signal input, data processing
      and storage. Methods for programming and results of introducing the developed
      software for research purposes are briefly discussed.

PMID- 8992187
TI  - [Experimental findings and a new screw endoprosthesis of the hip joint].
AB  - Based on his own experimental findings, the author provides strong evidence for
      negative consequences of the deranged vascular network of haversian systems while
      screwing the screw pedicles of hip joint endoprostheses into the endostalic
      margin of the cortical layer of the diaphysis. It is shown that it is not
      advisable to use a endoprosthetic assembly unit in the intertrochanteric area for
      biomechanical reasons. The latest endoprosthesis of the author's own design,
      which has a monolithic transition of the neck into the pedicle, is described,
      with emphasis on driving the endoprosthetic screw pedicle into the diaphysis
      rather than on its screwing. The prosthesis has a pedicle with a specific
      trapezoidal thread and a knock-down mobility unit.

PMID- 8992188
TI  - [Principles of monitoring food products by impedance Bactometer].

PMID- 8992189
TI  - [Ophthalmologic electromagnetic stimulator OFTEMAGS].
AB  - The design of an OFTEMAGS ophthalmological electromagnetic stimulator, its new
      therapeutical factor (the pulse low-frequency field combined with a static
      magnetic field), and its brief specifications) are dealt with. A procedure for
      treating eye diseases and recommendations how to use the therapeutical factor in
      ophthalmology are given.

PMID- 8992190
TI  - [Portable new-generation illuminator for endoscopic equipment with OC-150-03
      light guides].
AB  - A new-generation portable OC-150-03 illuminator has been proposed for endoscopic
      equipment with light guides. The specifications of the illuminator are presented.

PMID- 8992191
TI  - [Metrological support of clinical dosimetry].
AB  - The main requirement for the dosimetric support of radiation therapy for cancer
      disease is the necessity of keeping the high accuracy of dosimetric planning of
      radiation therapy. This dosimetric planning involves a number of components
      including the measurement of the supporting dose, the establishment of a correct
      orientation of a primary beam, the receipt of accurate data on the distribution
      of organs and tissues in the radiation area. In fact, in all the above components
      there are errors in the estimation of the basic values, which totally determine
      the total error in the dosimetric planning of radiation therapy. The paper
      analyzes the constituents of the errors and show their requirements to be met at
      the present stage of dosimetric works.

PMID- 8992192
TI  - Localized 1H NMR spectroscopy of rat spinal cord in vivo.
AB  - A movable, actively decoupled surface coil has been employed to obtain a
      localized 1H NMR spectrum from the lumbosacral spinal cord of a live Lewis rat. A
      volume selective 'VOSY' normally spelled out as 'volume selective spectroscopy'
      spectroscopy pulse sequence that incorporates 'phase ramped' selective RF pulses,
      has been used to minimize random phase jitter in the NMR signal as a result of
      the large frequency shifts required to locate the voxel in the center of the cord
      while using intense gradient pulses. Spectra from 13-microliters voxels in
      healthy rats and in rats inoculated with guinea pig spinal cord and complete
      Freund's adjuvant, resulting in experimental autoimmune encephalomyelitis, are
      shown.

PMID- 8992193
TI  - Application of 31P NMR spectroscopy to monitor chemotherapy-associated changes of
      serum phospholipids in patients with malignant lymphomas.
AB  - 31P spectra were obtained from 22 healthy volunteers and 35 patients with
      malignant lymphomas. Sera from patients were collected at the time of diagnosis
      and at several time-points during therapy. Long-term follow-up studies showed a
      good correlation between the 31P NMR spectra of sera and the clinically evident
      response of the disease to the chemotherapy. During therapy leading to remission
      resonance from phospholipids increased progressively resulting in spectra similar
      to those seen in normal sera. By contrast, in patients who did not respond to
      therapy the intensities of the phospholipid peaks remained relatively low or
      became progressively reduced as the disease progressed. To understand the source
      of the spectral differences, we also examined the concentrations of high-density
      lipoprotein, low-density lipoprotein, cholesterol, and triglycerides. In
      individuals responding to the treatment, both high-density lipoprotein and
      cholesterol increased to the point where they were statistically equivalent to
      those from healthy volunteers.

PMID- 8992194
TI  - Fast proton spectroscopic imaging employing k-space weighting achieved by
      variable repetition times.
AB  - A k-space weighted spectroscopic imaging (SI) method is presented that allows a
      reduction in the total data acquisition time by up to 55% compared with standard
      SI. The k-space weighting is achieved by varying the repetition time, thus
      realizing an inherent apodization that corresponds to a circularly symmetric
      generalized Hamming filter. The flip angle is varied with the repetition time to
      enhance the signal-to-noise ratio. These techniques were employed using a short
      echo time of 10 ms. In vivo measurements on healthy rat brain at 4.7 T were
      conducted, obtaining two-dimensional spectroscopic imaging data from a 25 x 25
      circularly reduced k-space area in as little as 5 min. The signal-to-noise ratio
      is sufficiently high to detect J-coupled resonances such as myo-inositol or
      glutamate/glutamine, demonstrating the ability to combine short acquisition times
      with comprehensive metabolic information. The T1 dependency of the apodization
      and the corresponding point spread function was evaluated by computer
      simulations. The achievable signal-to-noise ratio per unit time was compared with
      standard SI giving a parameter-dependent advantage of approximately 20% of the
      standard SI method.

PMID- 8992195
TI  - Simultaneous localized 1H STEAM/31P ISIS spectroscopy in vivo.
AB  - A sequence for simultaneous acquisition of 1H STEAM and 31P ISIS spectra is
      described, and 1H and 31P spectra obtained simultaneously from the same volume of
      interest in both a phantom and a volunteer are presented. The STEAM and ISIS
      parts of the sequence use a common gradient scheme that is also used during the
      localized shimming process, partially compensating for eddy current effects. It
      is demonstrated that this method of simultaneous multinuclear spectroscopy does
      not compromise the localization performance of the sequence.

PMID- 8992196
TI  - Fourier tracking of myocardial motion using cine-PC data.
AB  - A closed-form integration method is derived and analyzed for computing motion
      trajectories from velocity field data, particularly as measured by phase contrast
      (PC) cine MR imaging. By modeling periodic motion as composed of Fourier
      harmonics and integrating the material velocity of the tracked point in the
      frequency domain, this method gives an unbiased trajectory estimate in the
      presence of white measurement noise and eddy current effects. When applied to
      cine PC data, the method can incorporate compensation for the frequency response
      of the cine interpolation, offering a further improvement on the tracking
      accuracy. In simulation and phantom studies, the estimated trajectories were in
      excellent agreement with the true trajectories. Encouraging results have also
      been obtained on data from volunteers.

PMID- 8992197
TI  - 31P NMR measurements of the effects of unsaturated fatty acids on cellular
      phospholipid metabolism.
AB  - 31P NMR measurements on extracts prepared from a variety of cultured mammalian
      cell lines and primary rat hepatocytes have shown changes in the levels of
      several phospholipid metabolites after incubation of cells with unsaturated fatty
      acids. These data suggest a possible link between the accumulation of neutral
      lipid and the changes in phospholipid metabolite concentrations that have been
      observed in some tumor cells and other rapidly growing tissues such as the
      regenerating liver and mitogen-stimulated lymphocytes.

PMID- 8992198
TI  - Cerebrovascular changes in rats during ischemia and reperfusion: a comparison of
      BOLD and first pass bolus tracking techniques.
AB  - Both first pass bolus tracking of a susceptibility contrast agent and blood
      oxygenation level dependent (BOLD) sequences provide information on the tissue
      perfusion and the cerebral blood volume, but each sequence has its own particular
      limitations. In this article, both techniques were used to assess the
      cerebrovascular changes occurring in a rat model of focal cerebral ischemia with
      reperfusion after 2 h of ischemia. The blood oxygenation level dependent studies
      were performed before, during, and after 60 s of anoxia to observe the response
      of the tissue to a respiratory challenge. Both techniques were able to detect
      ischemia and reperfusion; however, first pass bolus tracking provided better
      sensitivity and was easier to interpret. Because the blood oxygenation level
      dependent sequence did not provide any additional information, bolus tracking
      would appear to be the method of choice for studies of cerebral ischemia with
      reperfusion.

PMID- 8992199
TI  - 1H magnetic cross-relaxation between multiple solvent components and rotationally
      immobilized protein.
AB  - Magnetic cross-relaxation spectra or Z-spectra are presented for water, acetone,
      methanol, dimethylsulfoxide, and acetonitrile in cross-linked bovine serum
      albumin gels. Each solvent studied, reports the same Z-spectrum linewidth and
      shape for the solid component that follows from solutions of the coupled
      relaxation equations. The Z-spectra demonstrate competition among solvents for
      specific protein binding sites. The rate of magnetization transfer in the
      rotationally immobilized protein environment is approximated by 1/T2 for the
      solid component, which is shown to account for the observed magnetization
      transfer rates in the systems studied. The temperature dependence of the Z
      spectra are different for water compared with the organic solvents. The cross
      relaxation efficiency in the organic solvents decreases with increasing
      temperature because molecules bind less well at high temperature. For water, the
      hydrogen exchange path becomes increasingly important relative to the whole
      molecule path with increasing temperature, which improves the net cross
      relaxation efficiency.

PMID- 8992200
TI  - Coherence transfer by isotropic mixing in Carr-Purcell-Meiboom-Gill imaging:
      implications for the bright fat phenomenon in fast spin-echo imaging.
AB  - It is well known that when compared to conventional spin-echo (CSE) imaging for
      equivalent effective echo times, fast spin-echo (FSE) imaging experiments yield
      higher signal intensities for coupled spin systems, such as that for lipid. One
      hypothesis put forth for this phenomenon is the removal of scalar coupling-based
      echo amplitude modulation by the FSE pi pulse train. This would result in the
      maintenance of signal intensity in the late echoes, with an overall increase in
      image signal when the multiecho train data is combined to form the image data. It
      will be shown that in images and spectra obtained from the final echo of a Carr
      Purcell-Meiboom-Gill (CPMG) pi pulse train, an increase in signal in coupled spin
      systems occurs, when compared to conventional single-echo images and spectra at
      identical echo times. One- and two-dimensional spectroscopy experiments confirm
      that it is the generation of an isotropic mixing Hamiltonian by the pi pulse
      train in FSE that is responsible for the increased signal in images of a simple
      AX system and of corn oil, a model for human fat. This relative increase in
      signal is due to the maintenance of in-phase magnetization in the coupled spin
      systems by this Hamiltonian. In CSE, the weak coupling Hamiltonian allows
      development of antiphase coherences which, in the presence of the line broadening
      due to the imaging gradients, result in signal loss.

PMID- 8992201
TI  - Ferritin effect on the transverse relaxation of water: NMR microscopy at 9.4 T.
AB  - Accumulation of ferritin, the iron storage protein, has been linked recently to
      aging and a number of pathologies. Noninvasive detection of iron storage by MRI
      relies on its extremely strong effect on water relaxation. The aim of this
      article is to characterize the effect of ferritin on transverse water relaxation
      in a high magnetic field, using an imaging Carr-Purcell Meiboom-Gill (CPMG)
      preparation sequence. Ferritin-induced water relaxation showed quadratic
      dependence on the iron loading factor, implying a paramagnetic mechanism.
      However, an additional zero order term was found, that could be due to the
      initial stages of the iron core loading. Significant enhancement of ferritin
      contrast was obtained at very short Tau CPMG durations. This approach for
      enhancing ferritin contrast was demonstrated by NMR microscopy of ferritin
      injected Xenopus oocytes, thus showing the feasibility of ferritin detection in a
      high magnetic field, even in systems with short transverse relaxation.

PMID- 8992202
TI  - Assessment of flow in the right human coronary artery by magnetic resonance phase
      contrast velocity measurement: effects of cardiac and respiratory motion.
AB  - Flow in the human right coronary artery was determined using magnetic resonance
      phase contrast velocity quantification. Two methods were applied to reduce
      respiratory motion: Imaging during breath holding, which is fast, and
      retrospective respiratory gating, which has a high temporal resolution (32 ms) in
      the cardiac cycle. Vessel cross-sectional area, through-plane velocity, and
      volume flow were determined in six healthy subjects. In-plane vessel displacement
      during the cardiac cycle, caused by cardiac contraction, was about 2-4 mm within
      a time frame of 32 ms in systole and early diastole. The motion resulted in
      blurring of images obtained during breath holding caused by the large acquisition
      time window (126 ms) within the cardiac cycle. Therefore, only with a high
      temporal resolution correct velocity images over the entire cardiac cycle could
      be obtained. The time- and cross-sectionally averaged velocity was 7 +/- 2 cm/s,
      and the volume flow was 30 +/- 10 ml/min.

PMID- 8992204
TI  - Quantitative magnetic resonance imaging of perfusion using magnetic labeling of
      water proton spins within the detection slice.
AB  - A technique for noninvasive quantitative magnetic resonance imaging of perfusion
      is presented. It relies on using endogenous water as a freely diffusible tracer.
      Tissue water proton spins are magnetically labeled by slice-selective inversion,
      and longitudinal relaxation within the slice is detected using a fast gradient
      echo magnetic resonance imaging technique. Due to blood flow, nonexcited spins
      are washed into the slice resulting in an acceleration of the longitudinal
      relaxation process. Incorporating this phenomenon into the Bloch equation yields
      an expression that allows quantification of perfusion on the basis of a slice
      selective and a nonselective inversion recovery experiment. Based on this
      technique, quantitative parameter maps of the regional cerebral blood flow (rCBF)
      were obtained from eight rats. Evaluation of regions of interest within the
      cerebral hemispheres yielded an average rCBF value of 104 +/- 21 ml/min/100 g,
      which increased to 219 +/- 30 ml/min/100 g during hypercapnia. The measured rCBF
      values are in good agreement with previously reported literature values.

PMID- 8992203
TI  - Detection and characterization of primary liver cancer in rats by MS-264-enhanced
      MRI.
AB  - A new MR contrast agent, MS-264 (Gd(1RS)-1-(p-butylbenzyl)-DTPA), was developed
      to achieve hepatobiliary specificity and its potential evaluated for detecting
      and characterizing liver tumors in rats with chemically induced hepatocellular
      carcinoma (HCC). In seven rats with 66 HCC lesions, enhancements of different
      abdominal organs and tumors were compared on T1-weighted images after intravenous
      administration of Gd-DTPA (0.3 mmol/kg) and MS-264 (0.05 mmol/kg). MR images were
      correlated with postmortem microangiographic and histological findings. An
      overall enhancement of different organs, which normalized within 24 h, was
      observed after Gd-DTPA and MS-264 injection. MS-264 caused a higher relative
      enhancement (RE) in liver (60%), compared with that of Gd-DTPA (40%), which
      resulted in a prompt negative contrast enhancement in 59 of 66 HCCs. All were
      moderately to poorly differentiated (Grades II-IV) tumors. Six of these 59
      negative contrast-enhancing lesions showed a positively enhanced peritumoral rim,
      which corresponded histologically to malignant infiltration (n = 2) or
      compression (n = 4). On the other hand, six well differentiated HCCs showed
      prolonged positive enhancement. However, one well differentiated HCC was not
      positively enhanced by MS-264, probably due to poor access of the agent to the
      lesion. In comparison to that of the precontrast images, enhancement with Gd-DTPA
      and MS-264 increased the number of detected lesions by 22 and 42%, respectively.
      In this animal study, MS-264 proved to be useful in detection and
      characterization of primary liver cancers.

PMID- 8992205
TI  - Rapid repetition of the "burst" sequence: the role of diffusion and consequences
      for imaging.
AB  - When the Burst pulse sequence (Hennig et al. MAGMA 1, 39-48 (1993)) is applied
      with elementary pulses of finite flip angle, a non-uniform longitudinal
      magnetization is created, in the form of a series of fine bands of saturated
      spins. Both during and after the pulse train, the molecules contained within
      these bands diffuse. In this paper a full description is given of the evolution
      of the non-uniform longitudinal magnetization subsequent to the pulse train and
      the theory is verified experimentally. The value of the diffusion coefficient
      influences strongly the signal obtained when the Burst sequence is repeated
      rapidly. The consequences of this for imaging are discussed and, in particular,
      for the so-called "frequency-shifted" Burst technique.

PMID- 8992206
TI  - Implementation of a fast gradient-echo SVD encoding technique for dynamic
      imaging.
AB  - In the paper, the results of a fast gradient-echo implementation of the singular
      value decomposition (SVD) encoding technique for dynamic imaging are presented.
      The method used is an adaptation with several critical modifications of a
      keyholetype approach previously proposed but not implemented. The method was
      tested by imaging the events following injection of a contrast agent into a
      phantom, producing a series of dynamic image updates. It is demonstrated that,
      for this type of application, the SVD encoding technique adequately follows
      dynamic changes with even a small number of encodes. The result is compared
      qualitatively to that obtained by standard Fourier-based keyhole imaging and is
      shown to provide improved spatial resolution of dynamic events when updating with
      the same number of encodes.

PMID- 8992207
TI  - Phase-modulated binomial RF pulses for fast spectrally-selective musculoskeletal
      imaging.
AB  - Two fat-suppressed three-dimensional gradient echo pulse sequences, FLASH and
      DESS (Double Echo in Steady-State), that have significantly reduced scan time
      compared with conventional chemical shift fat-suppression sequences are
      presented. This fat-suppression technique is based on selectively exciting water
      spins using a time-optimized binomial RF pulse pair at the water resonance
      frequency with a null in the excitation profile at the fat frequency. To minimize
      the total pulse length, the delay between the binomial components of the RF pulse
      is decreased from a standard jump-return implementation. To maintain the proper
      null frequency, the phase of the second RF pulse is shifted such that it returns
      the fat resonance back to its initial z position while further tipping the water
      spins. Nonselective phase-modulated RF pulse pairs can be implemented in 1.20 ms
      at 1.0 T, significantly reducing the minimum TR.

PMID- 8992208
TI  - Frequency resolved single-shot MR imaging using stochastic k-space trajectories.
AB  - A new single-shot stochastic imaging technique with a random k-space path that
      provides very selective filtering with respect to chemical shift or off-resonance
      signals of the investigated tissue is proposed. It is demonstrated that in
      stochastic imaging only on-resonance compartments are visible whereas frequency
      shifted compartments cancel to noise that is distributed over the whole image.
      This method can be used as a single-shot chemical shift selective imaging
      technique and allows to calculate frequency resolved spectra for each spatial
      position of the image based on a single signal acquisition. The single-shot
      stochastic imaging sequence makes high demands on the gradient system and the
      theoretical k-space trajectory is distorted by imperfect gradient performance.
      Therefore an additional k-space guided imaging technique that uses the true,
      measured k-space trajectory to correct artifacts generated by eddy currents and
      delay times of the rapid switched gradients is presented. In vitro and in vivo
      measurements demonstrate the successful implementation of single-shot stochastic
      imaging on a conventional MR scanner with unshielded gradient systems.

PMID- 8992209
TI  - Calculation of the magnetization distribution for fluid flow in curved vessels.
AB  - The signal intensity in magnetic resonance angiography (MRA) images reflects both
      morphological and flow-related features of vascular anatomy. A thorough
      understanding of MRA, therefore, demands a careful analysis of flow-related
      effects. Computational fluid dynamics (CFD) methods are very powerful in
      determining flow patterns in 3D tortuous vessels for both steady and unsteady
      flow. Previous simulations of MRA images calculated the magnetization of flowing
      blood by tracking particles as they moved along flow streamlines that had been
      determined by a CFD calculation. This manuscript describes MRA simulations that
      use CFD calculations to determine magnetization variation at a fixed point and,
      therefore, do not require streamline tracking to calculate the distribution of
      magnetization in flowing fluids. This method inherently accounts for uniform
      particle density, avoids problems associated with tracking particles close to the
      wall, and is well-suited to modeling pulsatile flow.

PMID- 8992210
TI  - Intensity correction of phased-array surface coil images.
AB  - Phased-array coils distribute the high signal-to-noise ratio (SNR) performance of
      their small component surface coils over the larger area covered by the entire
      array. The inhomogeneous sensitivity profiles of the component surface coils
      result in images with very high signal near the phased-array and decreased signal
      far from the array. This paper presents a postprocessing algorithm for correcting
      these coil-related intensity variations. The algorithm's performance was
      evaluated by correcting images of volunteers acquired with several different
      receive-only phased-array surface coils.

PMID- 8992212
TI  - A new design for a three-channel surface gradient coil employing a three
      dimensional finite element model.
AB  - A new design of a three-channel surface gradient coil (SGC) is presented. The
      optimal objective of this design is to minimize parasitic field gradients by
      modifying the wire arrangement in the individual coils. A 3D finite element (FE)
      model is employed to analyze the SGC's field predictions. The numerical analysis
      results of the new SGC design indicate improved field behaviors when compared
      with those of a previously reported SGC designed by Cho and Yi (J. Magn. Reson.
      94, 471-485 (1991)). To confirm the predicted improvement, two Gy (Y-axis)
      gradient coils, based on the old and new designs, have been constructed and
      installed in a General Electric CSI 2 Tesla MRI system with a 15-cm bore. Based
      on the resulting MR images, the new gradient coil configuration provides more
      uniform field gradients and less parasitic field gradients, which results in
      higher quality images than the previously reported SGC design. This paper also
      demonstrates the remarkable accuracy of the 3D FE simulation model.

PMID- 8992211
TI  - The effect of magnetization transfer in meniscal fibrocartilage.
AB  - Magnetic resonance imaging of the knee was performed in 28 patients (ages 15-72
      years), using a 1.5-T unit. Volume gradient echo (3D GRASS) acquisition with and
      without presaturation off-resonance RF pulse was used to evaluate magnetization
      transfer (MT) effects, determined by placing regions of interest on muscle, fat,
      hyaline, and fibrocartilage; the percent change in signal intensity was
      calculated and compared using a paired two-sample t test. An in vitro study of
      the normal meniscus from a cadaver containing a scalpel cut extending to an
      articular surface was performed to observe the relative improvement in contrast
      in the presence of a small meniscal defect. MR imaging of the specimen was
      performed using an Omega CSI 2.0-T system (General Electric Medical Systems,
      Fremont, CA). Analysis of clinical images resulted in signal loss, compared to
      that of the identically timed and tuned non-MT images of 47 +/- 5, 8 +/- 5, 49 +/
      5, and 57 +/- 7% for muscle, fat, articular cartilage and fibrocartilage,
      respectively. Application of MT improved the depiction of the artificially
      introduced meniscal defect. Meniscal fibrocartilage demonstrates significant MT
      effect after application of off-resonance RF presaturation, which may improve
      visualization of meniscal defects.

PMID- 8992213
TI  - Reproducibility of high spatial resolution proton magnetic resonance
      spectroscopic imaging in the human brain.
AB  - The application of proton (1H) magnetic resonance spectroscopic imaging (MRSI)
      allows for noninvasive, localized analyses of brain biochemistry; however,
      minimal work has been devoted to the evaluation of 1H MRSI reproducibility. This
      study examined the reproducibility of 1H MRSI from five normal subjects on two
      occasions, separated by 10 days. Reproducibility of the MR signal was evaluated
      in the context of automated shimming, automated processing, and accurate subject
      repositioning. Reliability measures for physicochemical indices (choline
      moieties, creatine, N-acetylaspartate, and myo-inositol) were moderately
      concordant across repeat studies. Gain variation and repositioning results were
      excellent. It has been concluded that 1H MRSI reproducibility is adequate for
      serial studies of brain metabolism.

PMID- 8992214
TI  - Expansion of the spectral bandwidth by spatial and chemical shift selective
      saturation in high-speed magnetic resonance spectroscopic imaging.
AB  - A new spectral bandwidth expansion technique for high-speed magnetic resonance
      spectroscopic imaging (MRSI) based on an echo-planar technique is presented. This
      expansion can be achieved by spatial and chemical shift selective saturation
      without increasing the total measurement time. In addition, displacement along
      the slice-select direction due to chemical-shift differences between the measured
      compounds is also suppressed. Experimental results are shown using a phantom
      consisting of benzene and acetone. High spatial resolution (1 x 1 mm2) and wide
      spectral bandwidth (1.5-1.8 kHz; the effective spectral bandwidth has been
      doubled) are obtained without the displacement along the slice-select direction.

PMID- 8992215
TI  - Alternate k-space sampling in EPI: compensation for T2* and adjustable T2
      weighting.
AB  - In this work, preliminary results are described for a modification of the MBEST
      sampling scheme such that image resolution can be increased while preserving
      image contrast. In this new approach, a single spin-echo is used in sampling k
      space. The basic idea relies on acquiring a conventional EPI image from the
      center of k-space and applying a pi pulse to permit the acquisition of the two
      outer edges of k-space. Using this new approach, it is possible to obtain an
      enhancement in EPI image resolution, while reducing the extent of T2* weighting.
      As a result, the resulting images possess reduced T2* contrast and suffer less
      signal loss from T2* effects such as spatial variations in susceptibility and
      field inhomogeneity.

PMID- 8992216
TI  - Temporal resolution improvement in dynamic imaging.
AB  - In some dynamic imaging applications, only a fraction, 1/n, of the field of view
      (FOV) may show considerable change during the motion cycle. A method is presented
      that improves the temporal resolution for a dynamic region by a factor, n, while
      maintaining spatial resolution at a cost of square root of n in signal-to-noise
      ratio (SNR). Temporal resolution is improved, or alternatively, total imaging
      time is reduced by reducing the number of phase encodes acquired for each
      temporal frame by 1/n. To eliminate aliasing, a representation of the signal from
      the static outer portion of the FOV is constructed using all the raw data. The k
      space data derived from this representation is subtracted from the original data
      sets, and the differences correspond to the dynamic portion of the FOV. Improved
      resolution results are presented in phantom studies, and in vivo phase contrast
      quantitative flow imaging.

PMID- 8992217
TI  - Characterization of the cerebral distribution of general anesthetics in vivo by
      two-dimensional 19F chemical shift imaging.
AB  - The distribution of two fluorinated anesthetics, halothane and isoflurane, in
      rabbit brain was mapped during the course of their uptake using 19F NMR chemical
      shift imaging techniques. Use of a short phase-encoding time and free induction
      decay acquisition minimized T2-related signal losses in two-dimensional chemical
      shift imaging. Localization of the brain and exclusion of surrounding tissues was
      achieved by the use of a surface coil. The spatial distribution of halothane and
      isoflurane in the brain was nonuniform and both anesthetics were detected
      predominantly in the cerebral cortex. During the early stages of uptake,
      anesthetic concentration in the brain was extremely low, but it continued to
      increase for several hours with sustained anesthetic delivery. Time-dependent
      variations in anesthetic concentration were observed in different brain regions.

PMID- 8992218
TI  - Assigning value to clinical information--a major limiting factor in the
      implementation of decision-support systems.
AB  - This paper deals with a major difficulty and potential limiting factor in present
      day decision support-that of assigning precise value to an item (or group of
      items) of clinical information. Historical determinist descriptive thinking has
      been challenged by current concepts of uncertainty and probability, but neither
      view is adequate. Four equations are proposed outlining factors which affect the
      value of clinical information, which explain some previously puzzling
      observations concerning decision support. It is suggested that without
      accommodation of these concepts, computer-aided decision support cannot progress
      further, but if they can be accommodated in future programs, the implications may
      be profound.

PMID- 8992219
TI  - Performance of multi-layer feedforward neural networks to predict liver
      transplantation outcome.
AB  - A novel multisolutional clustering and quantization (MCQ) algorithm has been
      developed that provides a flexible way to preprocess data. It was tested whether
      it would impact the neural network's performance favorably and whether the
      employment of the proposed algorithm would enable neural networks to handle
      missing data. This was assessed by comparing the performance of neural networks
      using a well-documented data set to predict outcome following liver
      transplantation. This new approach to data preprocessing leads to a statistically
      significant improvement in network performance when compared to simple linear
      scaling. The obtained results also showed that coding missing data as zeroes in
      combination with the MCQ algorithm, leads to a significant improvement in neural
      network performance on a data set containing missing values in 59.4% of cases
      when compared to replacement of missing values with either series means or
      medians.

PMID- 8992220
TI  - Determinants of homonym and synonym rates of record linkage in disease
      registration.
AB  - Reliable record linkage is an essential component of the quality of population
      based disease registration. Quality assessment of disease registries should,
      therefore, include quantitative approaches to describe the extent of record
      linkage errors. The homonym and synonym rates have been proposed for this
      purpose. The homonym rate quantifies the proportion of distinct patients excluded
      from registration due to erroneous linkage with other patients. The synonym rate
      quantifies the proportion of unrecognized duplicate notifications on patients
      already registered in the registry. This paper provides an algebraic assessment
      of the determinants of both rates. It is shown how the homonym and the synonym
      rate are determined by the discriminating power provided by the personal
      identifiers and the record-linkage procedure on the one hand and the specific
      circumstances of disease registration on the other hand, such as the number of
      patients in the registry or the number of notifications per case. All these
      factors should be taken into account when reporting and interpreting results of
      record-linkage studies, particularly if comparisons are made between the
      performance of record-linkage procedures in different environments.

PMID- 8992221
TI  - Systematic planning of clinical documentation.
AB  - All information obtained from a patient in the course of medical care is a
      potential part of clinical documentation. The documentation usually serves a
      number of different purposes. The task of a documentation system is to fulfil
      these purposes in a methodically correct manner and as economically as possible.
      This requires that the properties of the documentation system be planned
      systematically with a view to the goals pursued. To support systematic planning,
      a "documentation protocol" is proposed analogous to the "study protocol" used for
      controlled clinical trials. The individual sections of the proposed documentation
      protocol are described and the design options which exist in the corresponding
      planning phases are pointed out. Experience gained by the application of the
      documentation protocol is discussed.

PMID- 8992222
TI  - Object-oriented analysis and design of an ECG storage and retrieval system
      integrated with an HIS.
AB  - For a hospital information system, object-oriented methodology plays an
      increasingly important role, especially for the management of digitized data,
      e.g., the electrocardiogram, electroencephalogram, electromyogram, spirogram, X
      ray, CT and histopathological images, which are not yet computerized in most
      hospitals. As a first step in an object-oriented approach to hospital information
      management and storing medical data in an object-oriented database, we connected
      electrocardiographs to a hospital network and established the integration of ECG
      storage and retrieval systems with a hospital information system. In this paper,
      the object-oriented analysis and design of the ECG storage and retrieval systems
      is reported.

PMID- 8992224
TI  - The generic patient record: an alliance between patient documentation and medical
      informatics.

PMID- 8992223
TI  - Computer-aided diagnosis in jaundice: comparison of knowledge-based and
      probabilistic approaches.
AB  - The study reported in this paper is aimed at evaluating the effectiveness of a
      knowledge-based expert system (ICTERUS) in diagnosing jaundiced patients,
      compared with a statistical system based on probabilistic concepts (TRIAL). The
      performances of both systems have been evaluated using the same set of data in
      the same number of patients. Both systems are spin-off products of the European
      project Euricterus, an EC-COMAC-BME Project designed to document the occurrence
      and diagnostic value of clinical findings in the clinical presentation of
      jaundice in Europe, and have been developed as decision-making tools for the
      identification of the cause of jaundice based only on clinical information and
      routine investigations. Two groups of jaundiced patients were studied, including
      500 (retrospective sample) and 100 (prospective sample) subjects, respectively.
      All patients were independently submitted to both decision-support tools. The
      input of both systems was the data set agreed within the Euricterus Project. The
      performances of both systems were evaluated with respect to the reference
      diagnoses provided by experts on the basis of the full clinical documentation.
      Results indicate that both systems are clinically reliable, although the
      diagnostic prediction provided by the knowledge-based approach is slightly
      better.

PMID- 8992225
TI  - Cardiological database management system as a mediator to clinical decision
      support.
AB  - An object-oriented medical database management system is presented for a typical
      cardiologic center, facilitating epidemiological trials. Object-oriented analysis
      and design were used for the system design, offering advantages for the integrity
      and extendibility of medical information systems. The system was developed using
      object-oriented design and programming methodology, the C++ language and the
      Borland Paradox Relational Data Base Management System on an MS-Windows NT
      environment. Particular attention was paid to system compatibility, portability,
      the ease of use, and the suitable design of the patient record so as to support
      the decisions of medical personnel in cardiovascular centers. The system was
      designed to accept complex, heterogeneous, distributed data in various formats
      and from different kinds of examinations such as Holter, Doppler and
      electrocardiography.

PMID- 8992226
TI  - Classification systems in nursing: formalizing nursing knowledge and implications
      for nursing information systems.
AB  - The development of nursing information systems (NIS) is often hampered by the
      fact that nursing lacks a unified nursing terminology and classification system.
      Currently there exist various initiatives in this area. We address the question
      as to how current initiatives in the development of nursing terminology and
      classification systems can contribute towards the development of NIS. First, the
      rationale behind the formalization of nursing knowledge is discussed. Next, using
      a framework for nursing information processing, the most important developments
      in the field of nursing on formalization, terminology and classification are
      critically reviewed. The initiatives discussed include nursing terminology
      projects in several countries, and the International Classification of Nursing
      Practice. Suggestions for further developments in the area are discussed.
      Finally, implications for NIS are presented, as well as the relationships of
      these components to other sections of an integrated computerized patient record.

PMID- 8992227
TI  - The questions of medical informatics.
AB  - Each science is identified with the questions it raises with respect to its
      object of study. This paper discussed the formulation of the basic questions of
      medical informatics. From a historical point of view, it first dealt with the
      problems of medical computing. Thereby, three classical questions arose: How can
      existing computers and information technologies assist in medical activities?
      Which components of the mathematical apparatus of informatics can be used for
      solving medical problems, and how and what activities of a physician are subject
      to algoritmization? The present time raises a new circle of questions centered
      around the basic one: How is the information system of the human organism
      structured and how does it function? This question and others form the basis of a
      new trend in medical informatics.

PMID- 8992228
TI  - Leukocyte activity and tissue injury following ischemia-reperfusion in skeletal
      muscle.
AB  - Few studies have correlated the occurrence of leukocytes with the time course of
      ischemia-reperfusion (I-R)-induced tissue injury in skeletal muscle. The goal of
      this study was to test the hypothesis that leukocytes were responsible for not
      only the onset, but progression of parenchymal cell injury within skeletal muscle
      following no-flow ischemia. Thirteen male Wistar rats (150-250 g) were randomly
      allocated to either a control (no I-R; n = 3), I-R (n = 5), or a leukopenic I-R
      group (n = 5). Under halothane anesthesia, the extensor digitorum longus muscle
      was prepared for intravital microscopy to allow video recording of microvascular
      perfusion and leukocyte flow behavior following 3 hr no-flow ischemia of the
      hindlimb. Tissue injury was assessed as the ratio of ethidium bromide (impermeant
      dye)-labeled nuclei to bisbenzimide (permeant dye)-labeled nuclei (E/B). During
      reperfusion, the I-R group showed a progressive decline in the number of perfused
      capillaries (N(C)) (from 19.37 +/- 0.04 to 3.34 +/- 1.18), while leukopenic and
      control rats were not significantly different. In the I-R group, the number of
      rolling leukocytes increased from 4.05 +/- 1.93 to 14.77 +/- 1.33 at the onset of
      reperfusion and remained stable throughout the reperfusion period. The number of
      stuck leukocytes, in the I-R group, progressively increased from 1.41 +/- 0.01
      prior to ischemia to 4.66 +/- 0.01 at the onset of reperfusion to 11.96 +/- 0.01
      after 90 min. The index of tissue injury (EIB) increased asymptotically from 0.60
      +/- 0.02 to 0.95 +/- 0.01 after 90 min of reperfusion in the I-R group, while
      leukopenia significantly reduced both the magnitude of tissue injury (i.e., 35%
      reduction from untreated I-R group) and the onset of such injury. In spite of the
      benefit afforded by leukopenia, evidence of tissue injury persisted (20% above
      control baseline level). We conclude that although leukocytes were responsible
      for the onset of parenchymal injury in skeletal muscle following 3 hr no-flow
      ischemia they are not the sole mediators of such injury.

PMID- 8992229
TI  - Oxygen tension profiles in isolated hamster retractor muscle at different
      temperatures.
AB  - Oxygen tension (P0(2)) profiles within unperfused hamster retractor muscles were
      obtained at 25, 30, and 37 degrees by using sharpened, recessed oxygen
      microelectrodes. The microelectrode was driven vertically into freshly excised
      muscle lying on a flat, impermeable boundary inside a diffusion chamber.
      Intramuscular P0(2) profiles were measured as a function of electrode depth in 10
      mu m steps during both inward and outward penetrations when the upper surface of
      the muscles was exposed to humidified gases containing 10, 21, 50, and 100% 0(2).
      The ratio of the 0(2) consumption (M) to the 0(2) permeability (K, Krogh
      diffusion coefficient = D alpha, diffusion coefficient-solubility product) was
      estimated by curve-fitting the experimental steady-state distribution of 0(2)
      through muscles to the analytic solution of the diffusion equation assuming that
      M obeys zero-order kinetics and K is constant, uniform, and independent of P0(2).
      The ratios of M/K were independent of temperature and were found to be
      independent of surface P0(2) and muscle thickness. The average value of M/K was
      3.9 +/- 0.45 (SE; n = 30) x 10(5) mm Hg/cm(2), which is consistent with that
      estimated from previous measurements of M and D using different non-steady-state
      techniques (Bentley et aL, 1993). These results are consistent with other in
      vitro 0(2) consumption measurements (Sullivan and Pittman, 1984) and do not
      provide evidence for nonclassical respiratory activity in resting mammalian
      skeletal muscle.

PMID- 8992230
TI  - Fibroblasts are in a position to provide directional information to migrating
      neutrophils during pneumonia in rabbit lungs.
AB  - Previous findings have shown that pulmonary fibroblasts are associated with
      preexisting holes in the endothelial and epithelial basal laminae through which
      neutrophils appear to enter and leave the interstitium as they migrate from
      capillaries to alveoli. To determine their role in neutrophil migration,
      fibroblast organization within the interstitium was assessed by transmission
      electron microscope observations of serial-sectioned rabbit lung tissue.
      Interstitial fibroblasts were found to physically interconnect the endothelial
      basal lamina holes to epithelial basal lamina holes. Morphometric assessment of
      rabbit lung tissue instilled with Streptococcus pneumoniae revealed that
      approximately 70% of the surface area density of migrating neutrophils is in
      close contact (15 nm or less) with interstitial fibroblasts and extracellular
      matrix elements (30 and 40%, respectively). Although migrating neutrophils were
      close enough to adhere to both fibroblasts and extracellular elements, the
      interstitial fibroblasts are organized in a manner that would allow them to
      provide directional information to the neutrophils. A model illustrating this
      process is proposed.

PMID- 8992231
TI  - A new method for the assessment of tissue hemoglobin oxygenation in patients with
      chronic venous insufficiency.
AB  - Venous incompetence often leads to ulceration of the skin of the lower limb due
      to a disturbance of skin microcirculation. We investigated 10 healthy subjects
      and 18 patients with chronic venous insufficiency by means of a fast scanning
      reflection photometer and determined noninvasively the hemoglobin oxygen
      saturation (S(HB)) and the relative concentration of hemoglobin (C(HB)) in the
      skin of the forefoot and at the calf, 10 cm proximal of the inner malleolus
      during positional changes. In supine position no significant differences were
      found. During sitting and standing S(HB) dropped and was significantly lower in
      patients at both locations (calf, standing, patients 22.2 +/- 10.6% vs controls
      48.2 +/- 13.5%, P < 0.001). C(HB) increased in patients during standing from 0.71
      to 2.13 +/- 0.33 aU (in controls from 0.69 to 1.49 +/- 0.28 aU, P < 0.001).
      Activation of the muscle pump decreased C(HB) and increased S(HB) in patients and
      in controls. After the movements were stopped, S(HB) decreased again and fell to
      the initial low values eight times faster in patients (7.4 +/- 5.3 vs 57.5 +/-
      19.6 sec, P < 0.001). C(HB) increased four times faster in patients (7.2 +/- 6.1
      vs 29.9 +/- 13.6 sec). In sitting and standing positions hemoglobin oxygenation
      in the skin of the lower limb was markedly reduced in patients, but normal
      perfusion conditions were restored in supine position, indicating reversibility
      of the changes. Reflection oxymetry seems a valuable tool for the assessment of
      chronic venous insufficiency. The substantially reduced oxygenation of dermal
      hemoglobin in standing patients may contribute to the development of venous
      ulcers.

PMID- 8992232
TI  - Role of tumor vascular architecture in nutrient and drug delivery: an invasion
      percolation-based network model.
AB  - Delivery of diffusible nutrients and drugs in tissues is limited in part by the
      distance over which substances must diffuse between the vascular space and the
      surrounding tissues and by upstream losses prior to local delivery by the blood.
      By examining the fractal behavior of two-dimensional vascular networks in the
      murine dorsal skinfold chamber preparation, we have identified distinct
      architectural features of normal and tumor vascular networks that lead to
      fundamentally different transport behavior. Normal capillaries which are
      relatively straight and regularly spaced are well modeled by the widely used
      Krogh cylinder model. In contrast, the fractal dimensions of tumor vascular
      networks suggest that the tortuous vessels and wide range of avascular spaces
      found in tumors are better represented by invasion percolation, a well-known
      statistical growth process governed by local substrate properties. Based on these
      observations, we have constructed a percolation-based model of tumor vascular
      growth that enables us to predict the effects of network architecture on
      transport. We find that the number of avascular spaces in tumors scales with the
      size of the spaces so that there will exist a few large avascular spaces and many
      smaller avascular spaces between vessels. We also find that the tortuosity of the
      vessels, as reflected by the elevated minimum path dimension, produces regions of
      locally flow-limited transport and reduces flow through the tumor as a whole. Our
      model helps to explain the long-standing paradox that tumor vasculature has a
      higher geometrical resistance than normal vasculature despite increases in vessel
      diameter. A comparison to oxygenation measurements in normal and tumor tissues
      shows that our model predicts the architectural obstacles to transport in tumors
      more accurately than the Krogh cylinder model. Our results suggest that clinical
      interventions that yield more regular vascular geometry may be useful as a
      supplement to those that improve arterial availability or decrease rates of
      consumption by the tissue.

PMID- 8992234
TI  - Effects of oxygen tension on flow-induced vasodilation in porcine coronary
      resistance arterioles.
AB  - Vascular tone has been shown to be importantly influenced by flow-induced release
      of endothelium-derived vasodilators. The purpose of the present study was to test
      the hypothesis that in porcine coronary resistance-size arterioles, flow-induced
      vasodilation is sensitive to oxygen tension. Arterioles (55-150 mu m) were
      studied in vitro under conditions of constant intraluminal pressure to
      dynamically measure arteriolar diameter in response to changes in flow or,
      alternatively, in response to bradykinin under three conditions: hyperoxia (pO(2)
      400 mm Hg), normoxia (pO(2) 160 mm Hg), and hypoxia (p0(2) 40 mm Hg). Under
      conditions of constant pressure and no flow, hypoxia alone resulted in
      vasodilation that was blocked by the nitric oxide synthase inhibitor omega-nitro
      L-arginine methyl ester (L-NAME). Hypoxia did not alter the vasodilator response
      to bradykinin when compared to the vasodilator response to bradykinin during
      normoxia. During hyperoxia, flow-induced vasodilation was significantly reduced
      by either indomethacin, or L-NAME. Indomethacin and L-NAME combined completely
      abolished flow-induced vasodilation under conditions of hyperoxia. Under
      conditions of normoxia and hypoxia, indomethacin or L-NAME alone only partially
      blocked flow-induced vasodilation. No further inhibition was observed when
      indomethacin and L-NAME were combined. Glybenclamide failed to alter flow-induced
      vasodilation either alone or in combination with indomethacin and L-NAME. The
      results suggest that the mechanisms responsible for flow-induced vasodilation in
      coronary arterioles are complex and are different depending upon the oxygen
      tension. During hyperoxia, vasodilation is due to the combined actions of
      prostanoids and nitric oxide, while under conditions of normoxia and hypoxia,
      flow-induced vasodilation is the result of not only prostanoids and nitric oxide,
      but of another as of yet unidentified oxygen-sensitive endogenous vasodilator.

PMID- 8992235
TI  - Autoregulation in the human retinal circulation: assessment using isometric
      exercise, laser Doppler velocimetry, and computer-assisted image analysis.
AB  - Autoregulation of blood flow in response to changes in perfusion pressure is
      known to occur in a number of tissues including the human retina. Defective
      autoregulation may play a part in the pathophysiology of several retinal
      diseases. Laser Doppler velocimetry has been used to study retinal blood flow.
      Technically superior measurements are obtained from veins by this method but
      arterial measurements might provide additional information. The response of the
      normal human retina to an acute elevation of systemic blood pressure induced by
      isometric exercise was investigated in nine normal volunteers using laser Doppler
      velocimetry and computer-assisted image analysis. Measurements were taken from
      retinal veins and arteries. Autoregulation was demonstrated by an 8.4% rise in
      flow in response to a 34% rise in perfusion pressure (P = 0.0007) using data
      derived from veins and a 4.8% rise in flow in response to a 33% rise in perfusion
      pressure (P = 0.01) using data derived from arteries. Arteries constricted by
      3.4% (P = 0.002) and veins dilated by 1.6% (P = 0.02). Red cell velocity rose in
      veins by 5.0% (P = 0.008) and in arteries by 12.2% (P = 0.02). The variability in
      velocity change derived from veins (SD 3.4%) was lower than that from arteries
      (SD 12.1%). A similar pattern of flow change was found in both sets of data. This
      makes venous measurements more useful for obtaining statistically reliable
      results from these techniques.

PMID- 8992233
TI  - The configuration of fibrin clots determines capillary morphogenesis and
      endothelial cell migration.
AB  - In the living organism, capillary growth frequently occurs in a fibrin-rich
      extracellular matrix. The structure and the mechanical properties of fibrin clots
      are influenced by various macromolecules (i.e., hyaluronic acid and
      thrombospondin) and also by pH, ionic strength, and thrombin concentrations of
      the milieu in which they polymerize. The configuration (three-dimensional
      architecture) and the rigidity of fibrin clots correlate with their opacity
      measured by spectrophotometric absorbance readings at 350 nm. By using bovine
      pulmonary artery endothelial cells and bovine fibrinogen, we show here that
      transparent fibrin clots (A(350) < 1.0), polymerized at > or = pH 7.5 or in the
      presence of increased thrombin or sodium chloride concentrations, strongly
      stimulated capillary morphogenesis in vitro. In contrast, opaque fibrin gels
      (A(350) > 1.5), polymerized at pH 7.2 or in the presence of dextran, stimulated
      only the migration of endothelial cells but not capillary morphogenesis. We
      demonstrate that the angiomorphogenic effects of basic fibroblast growth factor
      (bFGF) and vascular endothelial growth factor (VEGF) are strongly dependent on
      the structure of the fibrin clots. Our findings suggest that bFGF/VEGF primarily
      stimulate the proliferation of endothelial cells, whereas the three-dimensional
      architecture of the fibrin matrix is decisive for capillary morphogenesis.

PMID- 8992236
TI  - Cerebral hemodynamic response to female sex hormones in the rat.

PMID- 8992237
TI  - Regional vs systemic responses to mental stress: a potential mechanism for non
      demand-related ischemia.

PMID- 8992238
TI  - A mathematical model of the vascular supply of tumors.

PMID- 8992239
TI  - [Collagenolytic enzymes synthesized by microorganisms].
AB  - The review uses data obtained by the authors and available in the literature to
      discuss microbial collagenolytic enzymes, widely employed in scientific research,
      biotechnology, and medicine. Collagenases differing in their structure and the
      specificity of their action on collagen fibrils were isolated from bacteria
      (including marine isolates), actinomycetes, and fungi. Collagenases produced by
      Clostridium histolyticum and Achromobacter iophagus are the best studied enzymes;
      both are metalloenzymes that contain Zn2+ in their active site and retain
      collagenolytic activity in the presence of Ca2+. Serine-type collagenolytic
      proteases were also found in microorganisms. These enzymes differ from "true"
      collagenases by the structure of their active site. Both serine proteases and
      metalloproteases with high collagenolytic activities were isolated from the
      culture liquids of Streptomyces and Actinomyces strains. The biosynthesis of
      collagenases is induced by the addition of various collagen-containing substrates
      to the cultivation medium.

PMID- 8992240
TI  - [Characterization of the lipopolysaccharide from the Pseudomonas fluorescens
      strain IMV 472 (biovar I)].
AB  - Lipopolysaccharide was isolated from dry biomass of the Pseudomonas fluorescens
      strain IMV 472 (biovar I) by the Westphal procedure and purified by
      ultracentrifugation. Fractions of the structural components of the
      lipopolysaccharide macromolecule-lipid A, the core oligosaccharide, and the O
      chain-were isolated and characterized. 3-Hydroxydecanoic, 2-hydroxydodecanoic, 3
      hydroxydodecanoic, hexadecenoic, octadecenoic, and hexadecanoic acids were
      identified as the main fatty acids of lipid A. The hydrophilic moiety of lipid A
      was found to include glucosamine, phosphoethanolamine, and phosphate. Glucose,
      galactose, rhamnose, glucosamine, galactosamine, alanine, phosphoethanolamine,
      and 2-keto-3-deoxyoctulosonic were identified in the core region of lipid A. The
      O-specific polysaccharide chain consisted of a repeating tetrasaccharide fragment
      that included two L-rhamnose residues, a D-fucose residue, and an N-acetyl-D
      glucosamine residue as a side substituent. Double immunodiffusion in agar and the
      lipopolysaccharide precipitation reaction revealed no serological interrelation
      between strain IMV 472 and P. fluorescens strains studied previously.

PMID- 8992241
TI  - [Lytic action of lysoamidase from Xanthomonas sp. correlates with the presence of
      the target ribitol teichoic acids in the cell wall of gram-positive bacteria].
AB  - Lysoamidase, a bacteriolytic complex from the culture liquid of Xanthomonas sp.,
      hydrolyzed the cells walls of Staphylococcus aureus, Streptomyces chrysomallus,
      and Streptomyces azureus, which contain ribitol teichoic acids in addition to
      peptidoglycan. The cell walls of Streptomyces roseoflavus, Glycomyces
      harhinensis, and Nocardiopsis dassonvillei, containing glycerol teichoic acids,
      were not hydrolyzed by lysoamidase. The extent of the hydrolysis of 20-h Str.
      chrysomallus cells and cell walls, containing 40% ribitol teichoic acids, was
      considerably higher than that of 40-h cells and cell walls, containing 15%
      teichoic acids. Homogeneous bacteriolytic enzymes of the lysoamidase complex
      (muramidase and two bacteriolytic peptidases) most efficiently hydrolyzed S.
      aureus and Str. chrysomallus cell walls, characterized by the highest content of
      ribitol teichoic acids, and did not hydrolyze purified peptidoglycan.

PMID- 8992242
TI  - [NAD-metabolizing capacity of Saccharomyces cerevisiae mutants].
AB  - The activity of the key enzymes of the salvage synthesis and degradation of NAD
      (nicotinic acid mononucleotide pyrophosphorylase and NAD glycohydrolase) was
      studied in Saccharomyces cerevisiae mutants selected earlier as potential
      producers of NAD. An enhanced NAD-producing ability of the mutants was shown to
      be related to their reduced NAD-degrading activity: thus, NAD glycohydrolase in
      mutants 110, 118, and 206 was inactive in all growth phases regardless of the
      level of NAD biosynthesis.

PMID- 8992243
TI  - [Morphologic and physiologic-biochemical characterization of Pseudomonas
      aeruginosa dissociation variants].
AB  - Populations of the hydrocarbon-oxidizing strain K-2 of Pseudomonas aeruginosa
      dissociate into R, S, and M variants. They differ in colony morphology, cell fine
      structure, and cell yields on synthetic medium with hexadecane and on nutrient
      broth mixed with wort (NB + W). The best growth on NB + W was shown by the R
      variant, while the highest cell yield on hexadecane medium (exceeding that of the
      original culture) was attained by the S variant.

PMID- 8992245
TI  - [A new description of the type strain of Halobacterium distributum].
AB  - The descriptions of strains assigned to the species Halobacterium distributum
      were supplemented with the results of chemo-and genotaxonomic studies. According
      to these data, H. distributum VKM B-1733, which was hitherto regarded as the type
      strain of H. distributum, cannot be assigned to this species. Instead, strain H.
      distributum VKM B-1739 is proposed as the type strain. It is also suggested that
      strain VKM B-1954 should be transferred to H. distributum.

PMID- 8992244
TI  - [Sensitivity of dissociation variants of Micrococcus luteus to the action of
      delta-endotoxins of Bacillus thuringiensis].
AB  - Endotoxins of Bacillus thuringiensis subsp. tenebrionis produced an antibiotic
      effect on three out of the four species of micrococci tested, showing an activity
      of 10-23 units/mg, comparable with that of bacitracin. The R variants of
      Micrococcus luteus were more than twice as resistant to the action of delta
      endotoxins as cells of the S and M types. Enhanced growth of the tested
      microorganisms at concentrations of antibiotics large enough to inhibit the
      growth of the S and M variants, but insufficient to suppress the R-variant, was
      shown to be determined by the intense development of the latter variant.

PMID- 8992246
TI  - [Catabolism of methylphosphonic acid and its physiological regulation in
      Escherichia coli].
AB  - It was found that methyl phosphonic acid (Pn) was degraded by different
      Escherichia coli strains, which utilized it as the sole phosphorus source with
      resulting methane formation. This ability was influenced by mutations in the
      regulatory genes of the pho regulon. Thus, Pn was not degraded by an E. coli
      mutant defective in the regulatory phoB gene, responsible for the induction of
      pho-regulon proteins during phosphorus starvation. The intensity of Pn
      degradation depended on the age and concentration of the inoculum. Preincubation
      of bacteria in the presence of Pn accelerated subsequent degradation of both
      methyl phosphonic acid and its esters. Cultures developing from a small amount of
      inoculum degraded Pn more efficiently than heavily inoculated cultures that
      underwent only one cell division. However, cultures heavily inoculated with
      adapted cells degraded Pn as efficiently as cultures developing from a small
      amount of inoculum. Aeration was an important factor regulating Pn degradation:
      Pn was degraded more efficiently under anaerobic conditions regardless of the
      amount of inoculum.

PMID- 8992247
TI  - [Characterization of B-type bacteriophages adsorbed on Pseudomonas aeruginosa
      pili].
AB  - Pilus-dependent B-morphotype bacteriophages isolated from various sources were
      studied. The adsorption of phages on Pseudomonas aeruginosa pili was proven.
      Electron-microscopic examination of the morphology of phages was carried out, and
      the adsorption properties were partially described. It was suggested that
      adsorption apparatuses of different pilus-dependent B-phages are alike with
      respect to structure and function.

PMID- 8992248
TI  - Towards partnership: health care delivery and medical education: a blueprint for
      change. Proceedings of the Eastern Mediterranean Regional Conference. Al Ain,
      United Arab Emirates, 29 January - 1 February 1995.

PMID- 8992249
TI  - Certification in postgraduate medical education.
AB  - This paper sets out some of the issues relating to certification of specialists.
      It first defines the purpose of certification as assuring the public of the level
      of competence of specialist practice. It then describes some of the issues
      involved, which include the assessment of competence, the need for public
      involvement, the issue of re-certification, and the problem of dealing with poor
      doctors. It concludes with a challenge to doctors to seize the opportunities and
      to enhance the quality of teaching and research in medical education.

PMID- 8992250
TI  - The Educational Commission for Foreign Medical Graduates: global efforts in
      graduate medical education.
AB  - In addition to its certification programme, which assesses the readiness of
      foreign medical graduates to enter graduate medical education programmes in the
      USA, the Educational Commission for Foreign Medical Graduates (ECFMG) is involved
      in a number of other programmes in international medical education. These
      include: (1) continuing to provide sponsorship for exchange visitors in graduate
      medical education programmes in the USA; (2) the development of a clinical skills
      assessment that is currently being introduced in pilot projects in the USA and
      abroad and will eventually become a component of the ECFMG certification process;
      (3) funding and administration of two fellowship programmes that provide foreign
      scholars (clinicians and basic scientists) with the opportunity to spend up to
      one year in a US medical school; (4) collaboration with the World Health
      Organization on the upcoming revised edition of the World Directory of Medical
      Schools; and (5) co-sponsorship, with the World Health Organization, of a
      consultation on quality medical education oriented towards attaining a global
      consensus on the definition and the elements of quality in medical education and
      on the most appropriate ways to evaluate quality.

PMID- 8992251
TI  - The hospital and the clinic.

PMID- 8992252
TI  - Settings for learning: the classroom/laboratory/skills laboratory.

PMID- 8992253
TI  - Settings for learning: the community beyond.
AB  - The primary objective of medical education to medical students should not be the
      recruitment of specialists or to provide instructions about highly sophisticated
      clinic medicine. Our responsibility towards them is rather to enable them to
      learn about medical practice in its most prevalent context, which is the
      community medical practice, and to contribute to their general medical education
      and the health welfare of their community. The health needed by the nation cannot
      possibly be provided by specialists. It is a task for all doctors. If we agree
      that the ultimate goal of medical education is to secure health and proper care
      (whether primary, secondary or tertiary) for the population, medical curricula
      and learning settings should be open for any modifications that ensure a proper
      approach to our patients' practicalities, resources and needs. A major
      modification involved in that process would be for the educational setting to
      move from the hospital into the community and doctors to acquire the skills and
      conviction of working as part of a health team, in which they are not necessarily
      the leaders. The main social target of the World Health Organization and its
      member states, and in fact the main goal of humanity, is 'Health for All by the
      year 2000' through primary health care (HFA/PHC). Health systems of countries
      will have to be reoriented, so that they are based on the PHC approach. Health
      personnel are needed to service those health systems which are relevant to the
      needs of HFA/PHC, and hence whose education should be relevant to this major
      goal. This does not mean that by the year 2000 doctors and nurses will provide
      medical care for everybody or that sickness and disability will be eradicated. It
      does mean, however, that health begins at home, in schools and in factories, and
      that health care services should be available in those places and should respond
      to the needs expressed in those places. It is there, where people live and work,
      that health is made or broken. It does mean that essential health should be
      accessible to all individuals and families in an acceptable and affordable way,
      and with their full involvement. Health personnel should be trained according to
      the plans of integrated health services and health manpower development (HSMD),
      with a view of placing at the disposal of the system the right kind of manpower,
      in the right numbers, at the right time, in the right place (WHO 1979, 1985,
      1987). Graduates of programmes based on problem-based, community-oriented tracks
      as opposed to the traditional track should certainly be able to: respond to the
      health needs and expressed demands of the community, work with the community,
      stimulate healthy lifestyles and self-care, educate the community as well as
      their co-workers, solve and stimulate the resolve of both individual and
      community health problems, orient their own as well as community efforts to
      health promotion, prevent disease, unnecessary suffering, disability and death,
      work in and with health teams, if necessary provide leadership to such teams,
      continue learning lifelong so as to keep competence up to date, and improve this
      competence as much as possible (Fulop 1990). A limited literature is available
      comparing innovative and conventional medical curricula, where the innovative one
      is based on problem-solving learning with a community-oriented track geared
      towards community needs (Schmidt 1983). This approach showed that the outcome is
      better, if directed towards the health needs of the community.

PMID- 8992254
TI  - International collaboration in postgraduate education.

PMID- 8992255
TI  - Using group methods.

PMID- 8992256
TI  - Global overview: state of health education in the world.

PMID- 8992257
TI  - The main challenges.
AB  - The last few decades have witnessed dramatic changes, not only in health, but
      also in all aspects of human life. From the social point of view, the individual
      and family are again becoming the focus of attention, and there is an increasing
      concern about socio-economic conditions and human rights. From the health point
      of view, morbidity and mortality patterns are changing and many people live
      longer and fewer people die. The reasons behind these changes are mainly the
      expansion in knowledge and technology and the concern about our lifestyles. These
      changes impact heavily on both medical education, the delivery of health
      services, and the cost of health care. Medical schools should respond by
      introducing changes in the medical education process and ensure the proper
      training of a new generation of doctors who are community- and socially oriented,
      capable of relating to the community and its needs. The health care system should
      also respond to these changes by restructuring its organization and finance to
      ensure quality in health care and that health services are not rationed according
      to an individual's ability to pay. There are apparent advantages in establishing
      close links between medical education and health care. Both systems and the
      community stand to gain from these links. Full integration of the two systems
      could be the final objective but should be preceded by careful study and
      experimentation.

PMID- 8992258
TI  - Distinctive features of the region.

PMID- 8992259
TI  - Role of the medical school.

PMID- 8992260
TI  - Patients and the public.

PMID- 8992261
TI  - The managerial revolution: medicine as a business.
AB  - Medicine and management should be more closely integrated not just at the level
      of health policy and health services management but also in matters of
      professional education and training. Learning is a continuous process from
      entering medical school to retirement and should reflect the transition from
      learning shaped by the curriculum to learning driven by the needs of the
      qualified professional in a career service post. The senior clinician does much
      more than practise clinically. He or she is a leader, a manager, a resource
      allocator, a teacher and team player. In these roles the values and priorities of
      the professional and the organization will not always coincide. In postgraduate
      training and in continuing medical education more joint activity should be
      developed around 'medicine for non-medical managers' and 'management for
      doctors'. Much of this shared learning and development will be local and problem
      based around local issues of quality, resources and priorities. However, the
      'regional' postgraduate dean will play an increasingly pivotal role in
      maintaining the balance between the needs of the individual and the organization.
      To achieve this objective of closer integration postgraduate medical education
      funding should be brought together under a national finance levy against
      purchasers and allocated through devolved budgets managed by 'regional'
      postgraduate deans against explicit performance criteria agreed between the
      professional organizations, universities and health services management.

PMID- 8992262
TI  - Role of the community in contemporary health professions education.

PMID- 8992263
TI  - Exploring models of cooperation.

PMID- 8992264
TI  - Medical education in the USA: lessons from the health care reform era.

PMID- 8992265
TI  - Partnership: health services and medical education.

PMID- 8992266
TI  - International financing for health and the role of the World Bank.

PMID- 8992267
TI  - Interprofessional cooperation.
AB  - This paper presents various views on interprofessional cooperation and discusses
      the significant components and desired outcomes of such a relationship.
      Historically, the nurse-doctor relationship has been fraught with conflict;
      however, the challenge is to dismantle this imbalanced relationship and fashion
      new interdisciplinary collaboration. Collaborative practice is an ongoing,
      dynamic process, requiring time to develop. The creation of true partnership
      demands energy and commitment. Collaboration, a relationship of interdependence,
      is built on respect and understanding of the unique and complementary
      perspectives each profession makes to achieve desired outcomes. The health
      literature abounds with issues associated with interdisciplinary collaboration.
      Essential elements of collaboration, advantages and barriers to collaborative
      affiliation, impact of collaborative practice, and changes in practice patterns
      among professionals of various disciplines are some of the issues highlighted.
      Several universities and medical centres support faculty-practice joint
      appointment and believe this collaborative affiliation will bridge the
      accountability gap and will enhance the educational and organizational goals. The
      problem-based learning curriculum is permeating nursing schools. This educational
      strategy is valuable in that students learn team collaboration. Many studies
      believe that practice questions can be addressed better by merging the talents of
      clinicians and those in the academic setting. The authors point out that research
      based knowledge is essential for clinicians to solve patient care problems.
      Favourable outcomes to collaborative practice outweigh the barriers. No doubt
      there is synergism when a new partnership is created which is the hallmark of a
      true interprofessional relationship. This affiliation must be nurtured and
      reinforced, for it holds great promise for enhancement of patient care and for
      providing job satisfaction in an increasingly complex and constraining world of
      health care.

PMID- 8992268
TI  - Reorienting teachers: defining goals, roles and methods.

PMID- 8992269
TI  - Health professions development.
AB  - Health professions development is an integral part of national health plans. It
      is influenced by various factors and should be continuously updated to meet the
      changing health situation and related disciplines of the country. There are three
      forms of establishing a health manpower development plan: a market-oriented form,
      a goal-achievement form and a normative form. A combination of all forms is best
      if carried out by a community-oriented team of academic health professions and
      health care providers. Although countries of the Eastern Mediterranean Region
      share many demographic, geographic, and sociocultural characteristics, there are
      marked differences in resources, health manpower structure and availability in
      health services. Health professional development plans should be formulated
      according to existing situations. Other factors influencing health manpower
      development in the future include political, social and economic trends, changes
      in morality and disease patterns, industrialization, availability of health
      services and academic institutions. Perspectives guiding planning for the
      development of various categories of health professionals are presented.

PMID- 8992270
TI  - The place of science in the health professions.
AB  - The central premise of this paper is that medical education today is being driven
      by intellectual and social imperatives to make fundamental changes in the way it
      prepares students to be the doctors of tomorrow. Fully aware that over the past
      50 years at least eight major national commissions in the USA alone have made
      similar claims, the present reality is such that the pressure for change has
      greater force than at any time since the beginning of the century, when the
      overall form of modern medical education was set. The new science base of
      medicine requires the activation of its students. Although medical educators have
      recognized for at least half a century that active student learning is preferable
      to the passive student roles of didactic methods, we no longer have a choice. Not
      only is the activated student a requisite for learning that is intrinsic to the
      new intellectual paradigm, it is necessary for its application in clinical
      practice. At the same time, it is important to recognize that the social
      organization of medical education is structured to resist the kinds of changes
      that are inherent to the basic knowledge and practice requirements of
      contemporary medicine. The modern medical centre contains vested bureaucratic and
      financial interests, shared by both scientists and practitioners, which form a
      highly resistent structural barrier to change.

PMID- 8992271
TI  - Progress in medical education.
AB  - Progress in implementing the World Federation for Medical Education Edinburgh
      Recommendations in all three phases of education--undergraduate, postgraduate and
      continuing--is dependent upon recognition of the need to manage dissatisfaction
      with the present, to have appropriate visions for the future, to have a
      management strategy for implementing change and to be cost-effective. The extent
      to which progress can be anticipated is reflected in the formula: Change =
      (Dissatisfaction x Vision x Process) > Cost We have to aim for a curriculum that
      will be more convenient, relevant, individualized to the need of each student or
      trainee, diagnostic--emphasizing self-assessment, interesting--taking account of
      motivation of students and doctors, systematic or planned and allowing for
      speculation and a consideration of the grey areas or uncertainties of medicine as
      well as the certainties.

PMID- 8992272
TI  - Training for skills.
AB  - The World Federation for Medical Education Summit in Edinburgh in 1993 called for
      bold, clear, attractive and feasible strategies to equip doctors with the skills
      for the future of health care. There was special emphasis on skills for problem
      solving, ethical and evidence-based medicine, effective communication, health
      promotion and illness prevention, and to educate and be educated. There were also
      skills for the shaping of the future of health services to form partnerships with
      other professionals and communities, to promote primary health care and to
      respond to culture and context. Strategies for effective training for skills
      include linking them to knowledge and attitude, selection of students of aptitude
      and motivation, training through practice with feedback, training teachers and
      assessors, and the reinforcement of skills after graduation. This presentation
      describes practical examples of these strategies in action to address each of the
      identified skills, all of them based on experience in the real world in Australia
      and Nigeria.

PMID- 8992273
TI  - Quality assessment and improvement: principles and application in the Eastern
      Mediterranean Region.

PMID- 8992274
TI  - The graduate exodus.

PMID- 8992275
TI  - Specialist training.
AB  - Specialist training must be reshaped to meet the challenges of new systems for
      the delivery of health care and rapid expansion in biomedical knowledge. An
      adequate and affordable supply of trained specialists and generalists able to
      deal with the health problems of populations served, is the responsibility of
      governments and policy-makers that fund and those who deliver graduate education.
      Clearly defined objectives for specialist training are needed, linked to planning
      for the medical workforce size. A balance between numbers of specialists and
      generalists is essential, although flexibility in programmes should allow
      individuals to change. Curricula for all specialties should be published.
      Strategies and methods for delivery of graduate education and training must be
      coherent with those of medical schools. Training should be planned and sequenced
      to meet the identified needs of individuals. Those who teach should themselves
      learn how to train and assess trainees. The location for training should reflect
      present and future clinical practice if disfunction between medical education and
      the health of populations served and their need is to be avoided. Specialist
      training should form the basis for continuing education by encouraging lifelong,
      evidence-based learning. Any reshaping of specialist training must be consistent
      with the continuum of medical education. Instruments for assessment of
      specialists in training have to be refined, based on action research. Ensuring
      mastery in the competencies of each component of the curriculum is essential.
      Those competencies will change in consequence of altered societal needs plus
      advances in technology and biomedical knowledge.

PMID- 8992276
TI  - Continuing medical education.
AB  - While continuing medical education (CME) is receiving increasing attention from
      medical educators and health administrators worldwide, many efforts need to be
      made to improve its performance and overall effectiveness. Traditionally, CME has
      depended primarily on periodic courses and conferences. These remain of unproven
      cost-effectiveness and often the choice of their content is not tailored to meet
      best the needs of the learners. It is proposed that CME activities be reshaped to
      depend more on supervised small-group tutorials in which the learner is an active
      participant in preparation and presentation. Moreover, instead of having CME
      activities take place once or twice a year in a distant location, a more
      practical format would be to plan additional activities more frequently, but less
      condensed, on an ongoing basis and preferably at the place of work all year
      round. Factors that may increase learner motivation would be to depend not only
      on attendance at CME activities but also on the introduction of assessment
      mechanisms that will measure objectively the actual desired advancement of the
      learners. Incentives for good learners and teachers need to be introduced. The
      cost of CME is heavy and can be a burden on health authorities and medical
      institutions. Contributions from the medical/pharmaceutical industry are
      acceptable provided quality control is assured and conflict of interest is
      avoided. Increasing use of computer-assisted teaching and modern
      telecommunication should, in the near future, help to reduce costs and improve
      effectiveness of most CME programmes.

PMID- 8992277
TI  - [Benign delayed puberty in boys].

PMID- 8992279
TI  - [A follow-up study in individuals subjected to ileo-cecal resection in infancy
      and childhood].
AB  - It is stated that the ileocecal valve delays the passage of ileal contents into
      the cecum and acts as a barrier against reflux and ascension of colonic bacterial
      flora into the small bowel: its resection may lead to bacterial colonization of
      the ileum and to abnormalities of intestinal motility, transit and absorption. In
      this study twenty individuals subjected in pediatric age (1 day to 11 years) to
      ileocecal resection have been evaluated from 2 to 19 years after surgery. Three
      patients underwent limited ileocecal resection, in four this was associated with
      a significant ileal resection, in five with extensive right colon resection and
      in eight with extensive ileal and right colon resection. Growth, stool habit,
      hematology and serum biochemistry were examined; all patients also underwent
      abdominal ultrasonography. In all body weight and height were within normal
      limits; seven had moderate diarrhea up to 18 months after surgery and two who
      required extensive intestinal resection (40 and 30 cm of small bowel left) had
      diarrhea until about 36 months after surgery: now all of them have daily fecal
      evacuation. Hematological, biochemical, urinary and fecal studies proved normal
      except in one treated with TPN who presented transaminases slightly increased and
      in three suffering from mucoviscidosis in whom steatorrhea with moderate
      alterations of fats and elevation of alkaline phosphatase and transaminases were
      present. Urinary and gall stones were not seen in anyone. In conclusion from this
      study it can be postulated that removal of ileocecal valve can be done safely in
      children.

PMID- 8992278
TI  - [Serum lactate-dehydrogenase isoenzymes in HIV positive children. A longitudinal
      study].
AB  - The impairment of humoral immunity with rapid turn-over of cellular B clones in
      children with HIV infection is known as well as the conduct of LDH isoenzymes in
      B cell lymphoproliferative diseases like Burkitt's lymphoma. Therefore, serum
      lactate-dehydrogenase activity (LD, EC 1.1.1.27) and its isoenzymes have been
      evaluated twice (within 12 months) in 11 children with HIV infection with respect
      to a control group (30 subjects). Furthermore, the relationship between those and
      other clinical and immunologic parameters (total lymphocytes, CD4/CD8,
      immunoglobulins, classification according to the Atlanta CDC 1987) has been
      studied. HIV infected children have shown a significant decrease in LD1 rates,
      which was directly correlated to CD4/CD8 values. After the follow-up, this
      correlation became even more significant. Thus, these findings may suggest the
      usefulness of LDH isoenzymes evaluation as a marker of disease activity in
      children with HIV infection.

PMID- 8992280
TI  - [Implementation of the pediatric services in the region of Piedmont. A Piedmont
      pediatric team].
AB  - A survey was carried out within the framework of the Association of Hospital
      Pediatricians (APO) on the implementation of the pediatric structure in Pediatric
      hospitals wards in Piedmont during 1990. There was a 100% adhesion rate. It was
      found that only in 7 out of 36 hospitals were children always admitted to the
      Pediatric Division irrespective of symptoms. In all remaining cases,
      hospitalisation was based on the pathology and therefore children were spread
      between pediatric and adult wards with a percentage of over 30% (it was only
      possible to verify this figure in a small number of hospitals). Children with
      surgical symptoms were admitted to adult wards for the entire duration of their
      hospital stay in 17 hospitals. Only in 7 hospitals were children with surgical
      problems given pre- and postoperative treatment in pediatric wards. In 18 out of
      36 hospitals children undergoing surgery were not even examined before the
      operation by a pediatrician. The implementation of the pediatric structure mainly
      depended on the behaviour of the PS DEA and therefore the fact that when a child
      entered hospital he immediately came into contact with the pediatrician. It was
      also found that average hospital stay in pediatric wards was 4.4 days (range 2.1
      7.4); the mean index of bed occupation was 50% (range 27.5-83.4). A pediatric
      doctor was on duty round the clock only in 10 out of 36 centres. In the majority
      of hospitals the number of beds destined for day-hospital activities was not
      specified. It is also worth pointing out that the number of neonatal cradles is
      never specified by the Regional Health Plan and there is no legal recognition of
      neonates admitted to the Nursery and, as a result, the number of neonatal medical
      staff is not quantified. A greater incisiveness of the current statutory
      requirements for the implementation of the pediatric structure might improve the
      level of assistance for children admitted to hospital.

PMID- 8992281
TI  - [Obstructive emphysema of infant during pulmonary tuberculosis].
AB  - A rare complication of pulmonary tuberculosis of infant is the obstructive
      emphysema following to the compression by enlarged lymphadenopathy. The authors
      report a case of obstructive emphysema observed in a 12 month old infant affected
      by pulmonary tuberculosis, and debate its more important pathogenethic, clinical
      and differential diagnosis aspects. At last they comment upon favourable clinical
      course observed as results of an exclusive medical treatment (antitubercular
      antibiotic therapy shortly combined with moderate corticotherapy) without making
      use of surgical, but aggressive, treatment.

PMID- 8992282
TI  - [Conservative treatment of post-traumatic hepatic hematoma. Case reports].
AB  - Post-traumatic hepatic haematomas may need surgical or conservative treatment. TC
      allows exact stadiation of hepatic lesions, detecting those mandatory for
      surgical approach. Haemodinamic unsteadiness and/or necessity of > 40 ml/kg blood
      transfusion suggest serious uncontrollable bleeding, that is surgical emergency.
      Three cases of post-traumatic heapatic haematomas recovered after conservative
      treatment (clinical, haematological and radiological survey) are described.

PMID- 8992283
TI  - [Recto-cutaneous penile fistula. A description of a clinical case and review of
      the literature].
AB  - This describes a newborn with an imperforate anus associated to a fistulous track
      extending along the scrotal raphe and opening at the penis top. This variant
      appears to be a low anomaly. The surgical treatment of this pathology is
      discussed.

PMID- 8992284
TI  - [Hepatic abscesses caused by Streptococcus intermedius].
AB  - Pyogenic abscess of the liver is uncommon child's pathology. The authors briefly
      describe a clinical picture characterized by beginning of an hepatic abscess dues
      to a germ that is not usually pathogen for men. It is often a mouth saprophyte.

PMID- 8992285
TI  - [Celiac disease associated with major thalassemia. A case report].
AB  - The spectrum of clinical manifestations of coeliac disease, the most common
      chronic intestinal disorder in children, has widened considerably over the past
      years and new associations with other diseases, both immunological and non
      immunological, have been described. AGA and EMA have proved to be an efficient
      screening method both in populations with gastrointestinal pathologies and in
      groups of pauci- or even asymptomatic subjects. The clinical picture of beta
      thalassemia has gradually altered over the years owing to improved treatment.
      However, growth is still affected in a considerable proportion of thalassemic
      patients. A number of hormonal and other causes, combined in varying ways,
      contribute to determining this clinical condition. The authors report a case of
      coeliac disease in an adolescent with thalassemia major characterised by
      anorexia, arrest of weight gain and low stature. The identification of a new
      association between coeliac disease and thalassemia major highlights the need to
      search for this pathology in all thalassemic patients who present scarce growth
      in stature and weight.

PMID- 8992287
TI  - [Lymph node excision in stomach cancer and clinical comparative tests].

PMID- 8992286
TI  - Alcohol use during pregnancy. How health care providers can make a difference.

PMID- 8992288
TI  - [The role of G-proteins in the specificity of cellular response: characteristics
      of alpha-subunit structure and function].

PMID- 8992289
TI  - [Expression of cDNA for human interleukin-8 type one receptor in BALB 3T3
      fibroblasts and characteristics of products of expression].

PMID- 8992290
TI  - [Nucleotide analogs modified in sugar residue in DNA synthesis reaction in
      vitro].

PMID- 8992291
TI  - [A model prokaryotic promoter. IV. Properties of constructs containing regular
      repeats of Pribnow sequence].

PMID- 8992292
TI  - [Pericentromeric alpha-satellite DNA in human chromosome 21 bordering with
      euchromatin DNA].

PMID- 8992293
TI  - [Construction of recombinant variants or orthopoxviruses by inserting foreign
      genes into intragenic region of viral genome].

PMID- 8992294
TI  - [The effect of Mg2+ and Ca2+ ions on the aminoacylation of of transcripts of
      bacteriophage T5 and Escherichia coli tRNA(Phe) genes].

PMID- 8992295
TI  - [Determination of the number of ribosomal genes in individual human genomes.
      Comparison of the results of molecular and cytogenetic analysis].

PMID- 8992296
TI  - [The effect of noncanonical structures on the expression of chimeric genes in
      eukaryotic cells: in vivo study].

PMID- 8992297
TI  - [SegE endonuclease from phage T4. I. Cloning, expression, and biochemical
      characteristics of endonuclease activity].

PMID- 8992298
TI  - [New structural motifs of DNA-ligand interaction: trimeric type of bis-netropsin
      complex with poly(da-dT).poly(dA-dT)].

PMID- 8992299
TI  - [Statistical analysis of correspondence between the primary and tertiary protein
      structure].

PMID- 8992300
TI  - [Three-stage equilibrium unfolding of small globular proteins by denaturing
      agents. I. Carboanhydrase B].

PMID- 8992301
TI  - [Three-stage equilibrium unfolding of small globular proteins by denaturing
      agents. II. Beta-lactamase and general model].

PMID- 8992302
TI  - [Synthesis and properties of covalently bound DNA-duplexes containing substituted
      pyrophosphate group between complementary chains].

PMID- 8992303
TI  - [Calculation of kinetics of hybridization of DNA with oligonucleotides fixed in a
      gel layer].

PMID- 8992304
TI  - [Conformational analysis of major antigenic determinant of HIV-1 gp120 protein
      using the NMR spectroscopy data].

PMID- 8992305
TI  - [Comparison of positions of attachment sites of DNA loops to nuclear matrix, MAR
      elements, and autonomously replicating sequences in the elongated region of
      Drosophila melanogaster X-chromosome].

PMID- 8992306
TI  - [Isolation, structural characteristics and functional properties of extracellular
      ribonuclease from Bacillus polymyxa].

PMID- 8992307
TI  - [Stoichiometry of phage T4 Dam-DNA-[N6-adenine]-methyltransferase binding with
      oligonucleotide substrates].

PMID- 8992308
TI  - [Spatial structure of light-harvesting chlorophyll-protein complex B800-850 from
      the photosynthesizing bacterium Rhodobacter sphaeroides].

PMID- 8992309
TI  - [Polyol-protein interactions. Microcalorimetric study of lactate dehydrogenase
      denaturation in aqueous solutions of glycerol].

PMID- 8992310
TI  - [Cell-free system for RNA replication, expression and cloning].

PMID- 8992311
TI  - [Can the enantiomer of the substrate be the substrate for the same enzyme?].

PMID- 8992312
TI  - Structural analysis of the glycosyl-phosphatidylinositol membrane anchor of the
      merozoite surface proteins-1 and -2 of Plasmodium falciparum.
AB  - Plasmodium falciparum accumulates the two merozoite surface proteins-1 and -2
      during schizogony. Both proteins are proposed to be anchored in membranes by
      glycosyl-phosphatidylinositol membrane anchors. In this report the identity of
      these GPI-anchors is confirmed by labelling with tritiated precursors and
      additionally by specific enzymatic and chemical treatments. Detailed structural
      analysis of the core-glycans showed that the GPI-anchors of both proteins possess
      an extra alpha 1-2 linked mannose at the conserved trimannosyl-core-glycan. MSP-1
      and MSP-2 labelled with tritiated myristic acid possess primarily radioactive
      myristic acid at inositol rings in both GPI-anchors. Additionally the hydrophobic
      fragments released from [3H]myristic acid labelled GPI-anchors were identified as
      diacyl-glycerols, carrying preferentially [3H]palmitic acid in an ester-linkage.

PMID- 8992313
TI  - Molecular characterization of a P-glycoprotein-related tcpgp2 gene in Trypanosoma
      cruzi.
AB  - We have cloned, sequenced and characterized a gene from Trypanosoma cruzi (Y
      strain), termed tcpgp2, which encodes a member of the ABC (ATP-binding cassette)
      superfamily of evolutionarily conserved transport proteins. The nucleotide
      sequence of the tcpgp2 gene was determined. It presents a 4602-bp open reading
      frame, coding for a 1534-amino acid protein, with a predicted molecular mass of
      169,470 Da. The deduced amino acid sequence of tcpgp2 exhibited a remarkable
      homology with the P-glycoprotein-related genes of Leishmania tarentolae, the
      yeast cadmium factor (YCF1) and the human multidrug resistance-associated protein
      (MRP). Southern blot analysis using a specific probe indicated that the Tcpgp2 P
      glycoprotein is encoded by a single copy gene which maps to a chromosome of about
      900 kb. Northern blot analysis revealed that tcpgp2 gene is expressed as a
      polyadenylated transcript of approximately 5 kb in dividing amastigote and
      epimastigote forms; we did not detect the transcript in the non-dividing
      trypomastigote forms of the parasite. Gene transfection experiments in Leishmania
      tropica indicated that, under the conditions tested, tcpgp2 gene is not involved
      in drug resistance.

PMID- 8992314
TI  - Metabolism of AF1 (KNEFIRF-NH2) in the nematode, Ascaris suum, by aminopeptidase,
      endopeptidase and deamidase enzymes.
AB  - We have studied the metabolism and inactivation of AF1 (KNEFIRF-NH2) by membranes
      prepared from the locomotory muscle of Ascaris suum. FIRF-NH2 and KNEFIRF were
      identified as three primary degradation products, resulting from the action of an
      endopeptidase, aminopeptidase and a deamidase, respectively. The endopeptidase
      resembled mammalian neprilysin (NEP, endopeptidase 24.11) in that the enzyme
      activity was inhibited by phosphoramidon and thiorphan and that it cleaved AF1 on
      the amino side of phenylalanine. The aminopeptidase activity was inhibited by
      amastatin and bestatin but not by puromycin. The deamidation of AF1 was inhibited
      by phenylmethylsulfonyl fluoride, p-chloromercuricphenylsulfonate and mercuric
      chloride, indicating that the deamidase enzyme is a serine protease with a
      requirement for a free thiol group for activity. AF1 (1 microM) induces an
      increase in tension and an increase in the frequency and amplitude of spontaneous
      contractions of an A. suum muscle strip. None of the aforementioned AF1
      metabolites (2-20 microM) retained biological activity in this bioassay,
      indicating that the endopeptidase, aminopeptidase and deamidase have the
      potential to terminate the action of AF1 on locomotory muscle of A. suum.

PMID- 8992316
TI  - Toxoplasma gondii expressed sequence tags: insight into tachyzoite gene
      expression.
AB  - Analysis of DNA sequences from the 5' end of 239 directionally cloned Toxoplasma
      gondii RH strain tachyzoite-derived cDNAs revealed significant similarity to
      several classes of genes/proteins including 24 ribosomal proteins, five metabolic
      enzymes, four cell-cycle regulators and 15 previously cloned T. gondii genes. The
      remaining sequences with no significant match include several which were
      recovered more than once. The variety and redundancy of expressed sequence tags
      (ESTs GenBank accession numbers T62239-T62475) in this sample suggest that the
      tachyzoite cDNA library reflects tachyzoite gene expression. A large scale EST
      effort should uncover many new genes and provide a wealth of information about
      genes involved with the growth and proliferation of tachyzoites.

PMID- 8992315
TI  - Development of a polymerase chain reaction assay for the diagnosis of neosporosis
      using the Neospora caninum 14-3-3 gene.
AB  - Neospora caninum is a recently described apicomplexan parasite which causes
      neuromuscular disease in dogs, and abortion and neonatal morbidity in cattle,
      sheep and horses. Morphological similarities and serological cross-reactivity
      between N. caninum and the closely related parasite Toxoplasma gondii, have
      resulted in the frequent misdiagnosis of neosporosis as toxoplasmosis. This
      report describes the isolation and characterization of an N. caninum cDNA clone
      encoding a 14-3-3 protein homologue. The 14-3-3 proteins are a class of proteins
      which show a high degree of amino acid sequence conservation across several
      eukaryotic taxa. Using less conserved regions of the N. caninum cDNA clone,
      nested primers were designed for the amplification of a 614-bp N. caninum DNA
      fragment by the polymerase chain reaction (PCR). The DNA fragment was amplified
      from N. caninum genomic DNA, but not from T. gondii, Sarcocystis muris,
      Sarcocystis tenella, or Sarcocystis cruzi genomic DNA. Additionally, the fragment
      was amplified from DNA prepared from the brains of N. caninum-infected mice, but
      not from the brain of a mouse infected with T. gondii. These results suggest that
      this PCR assay may be useful for the diagnosis of neosporosis.

PMID- 8992317
TI  - Tissue localization and stage-specific expression of the phospholipid
      hydroperoxide glutathione peroxidase of Schistosoma mansoni.
AB  - The tissue localization and the stage-specific expression of the phospholipid
      hydroperoxide glutathione peroxidase of Schistosoma mansoni (SmPHGSHpx) have been
      determined. An antiserum raised against the C-terminal region of the predicted
      protein sequence was used for immunocytochemical investigations. The native
      protein is expressed only in female and egg vitelline cells and is practically
      absent from male worm tissue. Western blot data confirmed these results and
      showed the complete absence of SmPHGSHpx from cercariae. However, Northern
      blotting indicated the presence of the corresponding mRNA at all life-cycle
      stages investigated. The sequence determination of the 5' flanking region of the
      SmPHGSHpx gene revealed the presence of an extended TATA box (5'-TAAATA-3') at 
      32, a possible CAAT box at -75 and a putative monomeric estrogen response element
      5'-GGTCAA-3' at position -486. In addition, direct and inverted repeat elements
      are present.

PMID- 8992319
TI  - Chitinase genes expressed by infective larvae of the filarial nematodes,
      Acanthocheilonema viteae and Onchocerca volvulus.
AB  - State-specific products of 220 and 75 kDa were identified by metabolic labelling
      of infective larvae of the filarial nematode Acanthocheilonema viteae in ticks.
      Synthesis was temperature sensitive, occurring at 27 degrees C but not at 37
      degrees C. These products were secreted 3-6 days after leaving the vector during
      post-infective development, but subsequent expression was not detected. The
      smaller protein with a pI of 6.2, was purified by two-dimensional electrophoresis
      and the N-terminal amino acid sequence was derived. This provisionally identified
      the protein as a chitinase, which was confirmed biochemically by glycol-chitin
      substrate gel electrophoresis. The polymerase chain reaction was used to amplify
      a product from a cDNA library of A. viteae infective larvae. The nucleotide
      sequence codes for a putative signal peptide of 20 amino acids and a mature
      protein of 504 residues (Mr 56 kDa), exhibiting 69% identity (81% similarity
      allowing for conservative substitutions) with the MF1 chitinase described from
      microfilariae of Brugia malayi. N-linked glycosylation may account for some, or
      all, of the discrepancy in Mr between the predicted polypeptide and the native
      parasite product (75 kDa). Primers based on the A. viteae sequence were used to
      amplify a related sequence from a cDNA library of Onchocerca volvulus infective
      larvae. The O. volvulus cDNA codes for a 20-amino acid signal peptide followed by
      477 residues with an Mr of 54 kDa, and shares 67% identity with the A. viteae
      chitinase (80% similarity allowing for conservative substitutions) and 69%
      identity with the B. malayi MF1 molecule. It is proposed that chitinases
      expressed by infective stages of these filarial nematodes may play a role in
      ecdysis during post-infective development.

PMID- 8992320
TI  - Purification and characterization of three larval excretory-secretory proteins of
      Dirofilaria immitis.
AB  - Two proteins were previously described in the excretory-secretory products (ES)
      collected from Dirofilaria immitis during the molt from the third stage to the
      fourth stage in vitro. The two proteins were purified using cation exchange and
      reverse phase HPLC. During the purification of these two proteins, a third
      protein was identified that co-migrated with one of the others during previous
      gel analysis. All three had molecular masses of 20-23 kDa as determined by Tris
      glycine SDS-PAGE and have been designated 20, 22L and 22U kDa proteins. The three
      proteins were digested with trypsin. Amino acid sequences were subsequently
      determined for four peptides and the N-terminus of the 20 kDa protein, five
      peptides of the 22L kDa protein and three peptides of the 22U kDa protein. The 20
      and 22L kDa proteins were quite similar based on sequence and purification
      characteristics. The 22U kDa protein, but not the 20 and 22L kDa proteins, was
      also identified in adult worms using tryptic mapping and amino acid sequencing
      techniques. Immunoblot analysis demonstrated that the 20 and 22L kDa proteins
      were specifically recognized by sera from dogs immune to infection by D. immitis
      but not by sera from infected non-immune dogs. The 22U kDa protein was weakly
      recognized by the same immune sera but not by the infected non-immune dog sera.
      Since the 20 and 22L kDa proteins appear to be larval specific, associated in
      time with the molt from L3 to L4 and are specifically recognized by immune dog
      sera, they are good vaccine candidates.

PMID- 8992318
TI  - Phylogeny of trypanosomes as inferred from the small and large subunit rRNAs:
      implications for the evolution of parasitism in the trypanosomatid protozoa.
AB  - Sequences of the small rRNA genes and partial sequences of the large rRNA genes
      were obtained by PCR amplification from a variety of vertebrate trypanosomes. The
      trypanosome species and hosts included Trypanosoma avium from a bird, T.
      rotatorium from an amphibian, T. boissoni from an elasmobranch, T. triglae from a
      marine teleost and T. carassii from a freshwater teleost. Phylogenetic
      relationships among these species and other representatives of the family
      Trypanosomatidae were inferred using maximum likelihood, maximum parsimony and
      evolutionary parsimony. The trypanosomatid tree was rooted using rRNA sequences
      from two species from the suborder Bodonina. All methods showed that the
      mammalian parasite, Trypanosoma brucei, constitutes the earliest divergent
      branch. The remaining trypanosomes formed a monophyletic group. Within this
      group, the bird trypanosome was grouped with T. cruzi, while the elasmobranch
      trypanosome and the two fish trypanosome species formed a group with an affinity
      to T. rotatorium. Our results provide no evidence for co-evolution of
      trypanosomatids and their hosts, either vertebrate or invertebrate. This suggests
      that evolution of trypanosomatids was accompanied by secondary acquisitions of
      hosts and habitats.

PMID- 8992321
TI  - Molecular cloning of a developmentally regulated protein isolated from excretory
      secretory products of larval Dirofilaria immitis.
AB  - Three proteins isolated from the excretory-secretory products (ES) of larval
      Dirofilaria immitis have been previously characterized and termed the 20, 22L and
      22U kDa proteins. Two of the proteins (20 and 22L) were produced and released
      around the time of the third molt and were specifically recognized by immune dog
      sera. An amino acid sequence common to both proteins was used to synthesize a DNA
      probe to molecularly clone these molecules from a 48-h third stage larval cDNA
      library. The DNA sequence of the isolated clones encoded a 17.5 kDa protein with
      a 21 amino acid hydrophobic leader sequence that when removed yielded a 15.3 kDa
      protein starting with the N-terminal sequence obtained from the 20 kDa protein
      and containing all sequences obtained from tryptic peptides of the 20 and 22L kDa
      proteins. It was hypothesized that the 20 and 22L kDa proteins were the same,
      differing only by a 21 amino acid hydrophobic leader sequence which was later
      cleaved. The calculated molecular masses were consistent with those determined by
      reducing Tris-tricine SDS-PAGE. Expression of the protein without the leader
      sequence was accomplished in Escherichia coli. Antiserum raised against the
      expressed protein demonstrated the presence of the protein in L3 and L4, but not
      in adults or microfilariae. Expression of the protein with the leader sequence
      using a baculovirus system demonstrated processing of the signal sequence at the
      same time as found in larval D. immitis ES. Sera from dogs immune to infection
      were reactive with the D. immitis proteins expressed in either E. coli or insect
      cells.

PMID- 8992322
TI  - A detailed mutational analysis of the VSG gene expression site promoter.
AB  - The African trypanosome Trypanosoma brucei is a protozoan parasite that causes
      the disease African sleeping sickness. The parasite avoids the host's immune
      response by the process of antigenic variation, or by sequentially expressing
      antigenically different cell-surface coat proteins. These proteins, called
      variant surface glycoproteins (VSGs), are expressed from a specific locus, the
      VSG gene expression site (ES). In an attempt to understand expression of VSG
      genes, we expanded on earlier investigations of the promoter that controls the
      large VSG gene expression site transcription unit. We studied VSG ES promoter
      function both in transient transfection assays, and after stable integration at a
      chromosomal locus. Analysis of closely spaced deletion mutants showed that the
      minimum VSG ES promoter fragment that gives full activity is extremely small, and
      mapped precisely to a fragment that contains no more than -67 bp 5' to the
      putative transcription initiation site. The promoter lacked an upstream control
      element, or UCE, an element found at the PARP promoter, and at most eukaryotic
      Pol I promoters. Furthermore, linker scanning mutagenesis demonstrated that the
      VSG ES promoter contains at least two essential regulatory elements, including
      sequences within the region -67/-60 and the region -35/-20, both numbered
      relative to the initiation site. An altered promoter with mutated nucleotides
      surrounding the transcription initiation site still directed wild-type levels of
      expression. In this study, the results were similar for both insect and
      bloodstream form trypanosomes, suggesting that the same basic machinery for
      expression from the VSG ES promoter is found in both stages of the parasite.

PMID- 8992323
TI  - Conservation of key amino acids among the cysteine proteinases of multiple
      malarial species.

PMID- 8992324
TI  - Identification of N-acetylspermidine in Leishmania amazonensis.

PMID- 8992325
TI  - Repetitive sequences within the first internal transcribed spacer of ribosomal
      DNA in schistosomes contain a Chi-like site.

PMID- 8992326
TI  - Characterization of the delta-aminolevulinate synthase gene homologue in P.
      falciparum.

PMID- 8992327
TI  - Carvedilol in patients with chronic heart failure.

PMID- 8992328
TI  - Carvedilol in patients with chronic heart failure.

PMID- 8992329
TI  - Subarachnoid hemorrhage and acute myocardial infarction.

PMID- 8992330
TI  - Acute renal failure.

PMID- 8992331
TI  - Acute renal failure.

PMID- 8992332
TI  - Acute renal failure.

PMID- 8992333
TI  - Famotidine to prevent peptic ulcer caused by NSAIDs.

PMID- 8992334
TI  - Famotidine to prevent peptic ulcer caused by NSAIDs.

PMID- 8992335
TI  - Diagnostic value of dysmorphic urinary red cells.

PMID- 8992336
TI  - Exercise for women.

PMID- 8992337
TI  - Accidental pneumothorax from a nasogastric tube.

PMID- 8992338
TI  - Prostate-specific antigen in black men.

PMID- 8992339
TI  - Prostate-specific antigen in black men.

PMID- 8992340
TI  - Prostate-specific antigen in black men.

PMID- 8992341
TI  - Prostate-specific antigen in black men.

PMID- 8992342
TI  - Bypass angioplasty revascularization investigation.

PMID- 8992343
TI  - Bypass angioplasty revascularization investigation.

PMID- 8992344
TI  - Bypass angioplasty revascularization investigation.

PMID- 8992345
TI  - Ritonavir and renal failure.

PMID- 8992346
TI  - Indinavir nephropathy.

PMID- 8992347
TI  - Physical and emotional problems of elite female gymnasts.

PMID- 8992348
TI  - Physical and emotional problems of elite female gymnasts.

PMID- 8992349
TI  - Physical and emotional problems of elite female gymnasts.

PMID- 8992350
TI  - Physical and emotional problems of elite female gymnasts.

PMID- 8992351
TI  - The effect of aggressive lowering of low-density lipoprotein cholesterol levels
      and low-dose anticoagulation on obstructive changes in saphenous-vein coronary
      artery bypass grafts.
AB  - BACKGROUND: Obstructive changes often occur in aortocoronary saphenous-vein
      bypass grafts because of atherosclerosis and thrombosis. We studied whether
      aggressive lowering of low-density lipoprotein (LDL) cholesterol levels or low
      dose anticoagulation would delay the progression of atherosclerosis in grafts.
      METHODS: We studied 1351 patients who had undergone bypass surgery 1 to 11 years
      before base line and who had an LDL cholesterol level between 130 and 175 mg per
      deciliter and at least one patent vein graft as seen on angiography. We used a
      two-by-two factorial design to assign patients to aggressive or moderate
      treatment to lower LDL cholesterol levels (with lovastatin and, if needed,
      cholestyramine) and to treatment with warfarin or placebo. Angiography was
      repeated an average of 4.3 years after base line. The primary angiographic
      outcome was the mean percentage per patient of grafts with a decrease of 0.6 mm
      or more in lumen diameter. RESULTS: As measured annually during the study period,
      the mean LDL cholesterol level of patients aggressive treatment ranged from 93 to
      97 mg per deciliter; with moderate treatment, the range was from 132 to 136 mg
      per deciliter (P<0.001). The mean international normalized ratio was 1.4 in the
      warfarin group and 1.1 in the placebo group (P<0.001). The mean percentage of
      grafts with progression of atherosclerosis was 27 percent for patients whose LDL
      cholesterol level was lowered with aggressive treatment, and 39 percent for those
      who received moderate treatment (P<0.001). There was no significant difference in
      angiographic outcome between the warfarin and placebo groups. The rate of
      revascularization over four years was 29 percent lower in the group whose LDL
      cholesterol level was lowered aggressively than in the group receiving moderate
      treatment (6.5 percent vs. 9.2 percent, P= 0.03). CONCLUSIONS: Aggressive
      lowering of LDL cholesterol levels to below 100 mg per deciliter reduced the
      progression of atherosclerosis in grafts. Low-dose warfarin did not reduce the
      progression of atherosclerosis.

PMID- 8992352
TI  - Transmission of hepatitis B to patients from four infected surgeons without
      hepatitis B e antigen.
AB  - BACKGROUND: Transmission of hepatitis B virus (HBV) to patients by infected
      surgeons who carry hepatitis B e antigen (HBeAg) has been documented repeatedly.
      In the United Kingdom HBeAg-positive surgeons are not permitted to perform
      certain procedures that carry a risk that patients might be exposed to the blood
      of a health care worker. There are no practice restrictions for carriers of
      hepatitis B surface antigen without detectable HBeAg, unless transmission has
      been demonstrated. METHODS: In four unconnected cases of acute hepatitis B,
      surgery was identified as a possible source, so we tested the surgical teams for
      serologic markers of HBV infection. In each case a surgeon was found to be
      infected with the virus. HBV DNA was amplified by a nested polymerase chain
      reaction from serum from the four infected surgeons and the four patients, and
      direct nucleotide sequencing of two regions of the HBV genome was performed.
      Alternative sources of infection were ruled out. Other patients on whom three of
      the surgeons had recently performed procedures were offered testing. RESULTS: All
      four surgeons were carriers of HBV, but none had detectable serum HBeAg. The
      nucleotide sequences of HBV DNA from the surgeons were indistinguishable from
      those from the corresponding patients. The screening of other exposed patients
      identified at least two other patients who had probably acquired hepatitis B
      infection from one of these surgeons. CONCLUSIONS: Surgeons who are carriers of
      HBV without detectable serum HBeAg can transmit HBV to patients during
      procedures.

PMID- 8992353
TI  - Prosthetic heart valves.

PMID- 8992354
TI  - Prosthetic heart valves.

PMID- 8992355
TI  - Prosthetic heart valves.

PMID- 8992356
TI  - Prosthetic heart valves.

PMID- 8992358
TI  - Secular trends in coronary atherosclerosis.

PMID- 8992357
TI  - Secular trends in coronary atherosclerosis.

PMID- 8992359
TI  - Secular trends in coronary atherosclerosis.

PMID- 8992361
TI  - Medicare home health care services.

PMID- 8992360
TI  - Medicare home health care services.

PMID- 8992363
TI  - Medicare home health care services.

PMID- 8992362
TI  - Medicare home health care services.

PMID- 8992364
TI  - Economic reforms and child health in China.

PMID- 8992365
TI  - Economic reforms and child health in China.

PMID- 8992366
TI  - Economic reforms and child health in China.

PMID- 8992367
TI  - Everest nails.

PMID- 8992368
TI  - [Chronic fatigue syndrome. Definition, diagnostic measures and therapeutic
      possibilities].
AB  - This article reviews the chronic fatigue syndrome (CFS), a disorder whose
      etiology is unknown. The diagnostic criteria proposed in 1994 by the CDC and the
      International Chronic Fatigue Syndrome Study Group are introduced. In contrast to
      widespread belief, there are no laboratory tests available to underpin the
      diagnosis of CFS; the diagnosis is made solely on the basis of clinical criteria.
      In the differential diagnosis, the exclusion of other conditions that can cause
      chronic fatigue, such as neuropsychiatric or sleep disorders, is of critical
      importance. In this context, the question as to whether CFS is a clinical entity
      that can be differentiated from psychiatric diagnoses, such as depression,
      somatoform disorder, or neurasthenia, is discussed. At the moment, there is no
      specific therapy for CFS. Therefore, therapeutic approaches are limited to
      symptomatic management of the concomitant sleep disturbances, pain, or
      psychiatric symptoms, such as depression. Patients may benefit from cognitive
      behavioral therapy, as this may help then to identify and exclude factors
      contributing to and maintaining chronic fatigue. An integrated medical and
      psychological approach should be adopted, with the aim of preventing significant
      secondary negative results of the illness, such as interpersonal conflicts or
      chronic disability.

PMID- 8992369
TI  - [Examination of psychological functions by functional imaging with positron
      emission tomography and magnetic resonance imaging].
AB  - Changes in regional cerebral blood flow (rCBF) during experimentally modified
      psychological activation can be measured using radioactive ligands with positron
      emission tomography (PET) and using magnetic resonance principles with functional
      magnetic resonance imaging (fMRI). With PET it is possible to determine not only
      rCBF, but also metabolic changes, as well as the density and binding of several
      neuroreceptors. This can be done in conjunction with psychological and
      pharmacological challenge. fMRI is an imaging technique for perfusion-based
      signal intensities of the brain which does not involve radioactivity and gives
      better anatomical and temporal resolution than PET. Under appropriate
      experimental conditions, subjects' behavior and experience can be modified while
      they are lying in a tomograph. These experiments can be used for the scientific
      investigation of cognitive constructs such as memory and attention, or emotional
      processes. In this review, both functional neuroimaging techniques are assessed.

PMID- 8992370
TI  - [Alzheimer dementia and normal aging. Clinical, neuroradiologic, neurophysiologic
      and molecular biology follow-up data].
AB  - A total of 30 patients with clinically diagnosed Alzheimer's disease and 55
      healthy, age-approximated controls were followed up over a 2-year period to
      compare the course of functional and cognitive impairment, quantitative
      morphological and functional brain changes. No remarkable changes were observed
      within the control group in any of these modalities. There were significant
      differences between patients and controls at the first examination: Mini-Mental
      State Examination (MMSE), 16.1 +/- 7.3 compared with 28.7 +/- 1.4; left lateral
      ventricle 2.7 +/- 1.1% versus 1.6 +/- 0.7% of the total intracranial volume;
      right lateral ventricle 2.7 +/- 1.4% versus 1.4 +/- 0.4%; absolute delta-power
      1.1 +/- 0.3 versus 0.9 +/- 0.2 microV2; and absolute theta-power 1.1 +/- 0.3
      versus 0.8 +/- 0.2 microV2 (means +/- standard deviation). In the patient group,
      scores on the Blessed dementia rating scale deteriorated from 10.6 +/- 6.1 to
      17.9 +/- 9.6; the MMSE decreased by 8.0 +/- 3.7; the left lateral ventricle
      volume increased by 0.9 +/- 0.7%, the right by 0.9 +/- 0.7% of the total
      intracranial volume; absolute delta-power increased by 0.2 +/- 0.4 microV2 and
      theta-power by 0.1 +/- 0.3 microV2. We could not confirm a relationship between
      age, age at onset or apolipoprotein E4 gene dose and the rate of clinical change.
      High initial Blessed dementia scores were correlated with more severe ventricular
      enlargement, and delta-theta increase during the follow-up period. High initial
      theta-power predicted more severe functional and cognitive deterioration. To our
      knowledge, this is the first longitudinal study reporting quantitative clinical,
      morphological and EEG-changes measured in two points in time in patients and non
      demented controls.

PMID- 8992371
TI  - [Psychiatric morbidity in the oldest old. Results of the Berlin Aging Study].
AB  - An increasing life expectancy leads to a higher number of persons aged 70-84
      years and persons aged 85 years and older. Information concerning changes in the
      spectrum of psychiatric morbidity is rare. The Berlin Aging Study was based on a
      representative age- and gender-stratified sample (n = 516) of Berlin citizens
      aged 70-100 years and older. In this inter-disciplinary study, an intensive
      investigation was carried out by psychologists, sociologists, internists and
      psychiatrists. This report focuses on subjectively reported complaints
      (Beschwerdeliste, BL), observed psychopathological symptomatology (Brief
      Psychiatric Rating Scale, BPRS) and psychiatric diagnoses following the criteria
      of DSM-III-R (based on the Geriatric Mental State Examination, GMSA). On the self
      rating scale (BL) 10% of all persons reported severe subjective complaints, 32%
      moderate complaints. On the BPRS, 17% showed severe psychopathological
      symptomatology, 75% at least mild symptoms. Following the criteria of DSM-III-R,
      23.5% of all persons had a psychiatric disease, 4.2% a disease of severe
      intensity. When the DSM-III-R diagnoses "Not Otherwise Specified" (NOS) were
      included 40.4% of all subjects were diagnosed by the clinical judgement of the
      psychiatrists to have a psychiatric disease. The most frequent psychiatric
      diseases were insomnia (18.8%), depression NOS (17.8%) and dementia (13.8%).
      Dementia showed the well-known age-related increase, whereas no other incidences
      of psychiatric morbidity were age-related. Persons aged 70-84 years did not
      differ in the investigated psychiatric variables from persons aged 85 years and
      older, the only exception being the prevalence of dementia.

PMID- 8992372
TI  - [The German Alzheimer Family Groups. An assessment of current status].
AB  - Counselling the relatives of psychiatric patients is becoming increasingly
      important. This includes the relatives of patients with Alzheimer's disease.
      Since little is known about the organization and function of support groups for
      family caregivers of Alzheimer patients, in 1994 we wrote to all such groups
      known to us and asked them to fill in a questionnaire. The response rate was 85%
      (84/99), and 66 of the forms could be used for further analysis. The results were
      as follow: Most groups for relatives of Alzheimer patients admitted new members
      at any time. 69% had existed for more than 1 year and 19% for more than 5 years.
      81% consisted of 6-15 participants. 73% of the groups met once in a month. Health
      professionals organized the groups in 65% of cases. The main topics were trading
      information about the disease and support as well as daily care requirements. 73%
      of the groups were associated with health institutions or nationwide support
      organizations. Public relations were managed by personal contacts and press
      reports; did the groups rarely advertise. Based on a review of the literature,
      the impact of structure upon the function of groups is discussed.

PMID- 8992373
TI  - [The attitude of medical students to psychiatric patients].
AB  - Numerous studies conducted during the past decades indicate that the public's
      attitude toward the mentally ill is strongly prejudiced. Since the attitude of
      the general public also has an effect on community-based psychiatric care, we
      must ask how public opinion might be influenced. One possible approach could be
      through so called key community leaders--those who are highly respected in
      society because of their competence in a particular area. Doctors belong to this
      group of people. For this reason we questioned medical students, as future key
      community leaders, with respect to their attitudes toward the mentally ill within
      the framework of their first contact with psychiatric patients during their
      studies. In order to make a direct comparison possible, we interviewed a sample
      of the Mannheim population who live in a part of the city where a variety of
      complementary facilities have been set up. The comparison shows that medical
      students do not have a more positive attitude toward the mentally ill; in fact,
      in certain areas they have an even more negative attitude toward the mentally ill
      than the general population has. We were not able to establish what effect
      teaching has with respect to changing attitudes.

PMID- 8992374
TI  - [Patient satisfaction--artefact or social reality?].
AB  - The concept of patient satisfaction has become an independent evaluation
      criterion in the context of quality assurance. A review of patient satisfaction
      surveys referring to consumer satisfaction as a relevant health care concept,
      mostly being conducted in the USA, identifies numerous theoretical and
      methodological deficiencies. A consistently high level of patient satisfaction is
      reported, which is difficult to interpret. This requires critical analysis of
      what is meant by the term "satisfaction", considering theoretical concepts of
      satisfaction taken from various research areas. The paper concludes by pointing
      out that the concept "patient satisfaction" as it is used at present should not
      be seen as a valid indicator for the quality of care.

PMID- 8992375
TI  - ["Pyromania" and arson. A psychiatric and criminologic data analysis].
AB  - We analyzed psychiatric and criminological data from 103 arsonists. The following
      criticisms of the definition of pyromania according to DSM-III-R and IDC-10 seem
      appropriate. First, the categoric exclusion of aggressive motives does not seem
      very promising, since approximately one fourth of arsonists whose firesetting is
      based on motives quoted in DSM-III-R may also have an aggressive motive. Second,
      ICD-10 gives being drunk and alcoholism as a criterion for the exclusion of
      pyromania. This seems untenable, since the behavior classed as pyromania is
      largely a product of alcohol misuse. Repeated firesetting, resulting from being
      fascinated by fire etc., may be less a disturbance of impulse control but rather
      the manifestation of a psychoinfantilism, which, supported by alcohol abuse,
      extends into older age. The mean age of such arsonists is slightly above 20
      years. The tendency for relapses after imprisonment seems to be low; this
      tendency probably decreases spontaneously in older age. The mean age of arsonists
      with aggressive motives is a little below 30 years, those setting fire with
      suicidal motives have a mean age of 35, deluded arsonists have a mean age of 40
      years. Concrete sexual motives are relatively rare. Approximately 50% of
      arsonists have a purely aggressive motive. Retaliation is a rare cause, however,
      since most of them do not even know the victims. One third of these persons set
      the fire in their own homes. Most arsonists show a personality disorder, with
      insecurity and narcissism predominating. Data on firesetting are to be treated
      with caution, since two thirds of all cases are newer resolved; one fourth of
      cases concern minors, and in Central Europe arsonists with rational motives are
      hardly ever referred to psychiatrists.

PMID- 8992377
TI  - [Delusion of mercury poisoning in multiple sclerosis].
AB  - We confirmed the diagnosis of multiple sclerosis in a 54-year-old man. The
      patient rejected this diagnosis and was completely convinced that all his
      symptoms resulted from a chronic mercury intoxication. We found evidence that
      this delusional disorder was an independent illness, and not a "symptomatic
      psychosis in multiple sclerosis." So far, little notice has been taken in
      psychiatry of delusions of environmental poisoning, which cause difficulties in
      applying common criteria of delusion.

PMID- 8992376
TI  - [Subarachnoid hemorrhage from the anterior communication artery in a sex
      offender. Considerations regarding liability].
AB  - A 32-year-old man was accused of attempted rape. While urinating at the side of
      the road he felt an erection. He approached a 9-year-old girl who happened to be
      coming along and pressed his penis between her legs until ejaculation. Shortly
      afterwards he was arrested. He confessed, but claimed partial amnesia and had no
      explanation for the offence, which he normally would never have thought of.
      Shortly before the event a witness had seen him nearby in a poor state of
      orientation. Three months later in prison he suffered massive subarachnoidal
      hemorrhage from an aneurysm of the anterior communicating artery. The evaluation
      of his legal responsibility must take account of a putative psychomotor seizure
      at the time of the offence. With regard to the aneurysm diagnosed later, a
      pathogenetic connection, in terms of a preceding warning leak, might be assumed.

PMID- 8992378
TI  - [Somatic illnesses in psychiatric patients. 9 case reports].
AB  - We report nine case histories of patients admitted to a psychiatric hospital for
      severe somatic disorders. The somatic disease was either the cause of the
      psychiatric symptomatology, or it occurred in addition to a well-known
      psychiatric disorder. For general practitioners and psychiatrists it can be
      difficult to differentiate between symptoms due to psychiatric disorders and
      symptoms that indicate somatic disorders. If patients refuse the necessary
      diagnostic or therapeutic procedures and show behaviour that is not related to
      good health, there is increased risk for complications and increased morbidity.

PMID- 8992379
TI  - [Familial clustering of conversion disorder].
AB  - This paper reports the result of a study conducted in a single family, in which
      members of three generations were affected by a conversion disorder. The
      phenotype and the age of onset were very similar in all the family members
      affected. The etiology is best understood in terms of a genetic condition and as
      the result of imitation and identification with an affected family member.

PMID- 8992380
TI  - [Psychiatric problems in bone marrow transplantation patients during isolation].
AB  - Psychological stress is extremely high in patients with oncological diseases.
      About 50% of all cancer patients show psychological signs and symptoms which are
      related to the multiple stress factors of their oncological illness. Although
      many psychological problems connected with cancer are well known, additional
      acute stress could result from new therapeutic strategies which require settings
      similar to intensive care, e.g. bone marrow transplantation. For 2 years the
      Department of Psychiatry in Innsbruck has provided a "liaison service" at the
      Department of Bone Marrow Transplantation. Within this observation period, 40
      patients have received psychooncological care. The diagnostic distribution
      according to DSM III-R and specific psychooncological interventions are
      presented.

PMID- 8992381
TI  - [Opiate withdrawal in anesthesia (forced narcotic withdrawal, "turbo withdrawal")
      in narcotic dependence. Changes in withdrawal treatment--wishes and reality].

PMID- 8992383
TI  - [Peritonitis yesterday and today: trends in diagnosis and therapy].

PMID- 8992382
TI  - Visualization of protein kinase activities in single cells by antibodies against
      phosphorylated vimentin and GFAP.
AB  - Vimentin and glial fibrillary acidic protein (GFAP) are intermediate filament
      proteins expressed in the cytoplasm of various types of cells. The head domains
      of these proteins are phosphorylated by various protein kinases. Site- and
      phosphorylation-specific antibodies which recognize a phosphorylated
      serine/threonine residue in the head domains and its flanking sequence provide a
      useful tool to monitor and visualize protein kinase activities in single cells.

PMID- 8992384
TI  - [General surgery in the octogenarian patient. One year's clinical experience].
AB  - BACKGROUND: As the number of people over the age of 80 years is rapidly
      increasing, it may be expected that demand for surgical care for the elderly will
      also rise during the next decade thus contributing to a change in surgeon
      attitude. AIM OF THE STUDY: Because little literature is available on the
      surgical care requested by the over eighties, the aim of this study is to focus
      on the present surgical demand of the octogenarians in general surgical practice.
      METHODS: Two hundred-five admissions of 187 patients of above 80 years during one
      year were recorded retrospectively and statistical evaluation (Fisher exact test
      or Chi square test) of main clinical features was performed. RESULTS: The rate of
      surgical admission of octogenarians was 6.5% (205/3135). Half of the patients
      were admitted as emergencies (52.7%). This percentage was significantly higher (p
      < 0.000) than in < 80 year old patients (20.8%). The mortality rate for all
      admissions was 11.2%. In 65.4% of cases a surgical procedure was necessary with a
      correlated mortality rate of 8.2%. The mortality (2.9%) and morbidity (17%) rate
      in elective surgery were significantly lower (p = 0.0176 and p = 0.003
      respectively) than in emergency surgery (13.6% and 42% respectively). Of all
      admissions 74.4% were uneventful and, in patients who underwent surgery,
      complications occurred in 29.8% with no statistically significant differences
      between patients with or without coexisting disease. The mean hospital stay was
      11.4 days and in operated patients was 14.4 days. Almost the total number of
      patients could be sent home directly. CONCLUSIONS: In octogenarians, surgery is
      performed more frequently when a complication occurs, but this attitude should be
      changed because the mortality and morbidity rate are significantly higher. New
      standards of management and new resources will be requested for the elective
      surgical care of this rapidly increasing aged group of patients.

PMID- 8992385
TI  - [Dynamic ultrasonography in the assessment of candidates to laparoscopic
      cholecystectomy].
AB  - Laparoscopic surgery has opened a new era in the management of surgical diseases.
      But, on the other hand, has created problems relating to the technological and to
      the technico-surgical aspects. In the preoperative evaluation of laparoscopic
      cholecystectomy candidates it is very important to know about the pathological
      state of the gallbladder, which may become the cause of very difficult or
      impossible laparoscopic operation, and the convert in an open procedure will be
      forced. Recurrent gallbladder inflammations provoke alterations of the normal
      structure of the wall (oedema, fibrosis) and normal elasticity and contraction
      after stimulation is last. Adhesion with neighbouring organs hinder contraction
      as well, and surgical difficulties increase. Choledocholithiasis must be known
      before operation, to plan surgical strategy. The presence of choledochus disease
      does that allow us to modify its calibre after stimulation. 100 patients who
      underwent laparoscopic cholecystectomy, in our Department, were evaluated before
      with dynamic ultrasonography (DUS), and the results were compared with operating
      finds. In this paper are exposed the used method of evaluation and the results of
      this work. These results allow as to state that the method is effective and
      trustworthy.

PMID- 8992386
TI  - [Biliary ileus: pros and cons of the most current diagnostic methods].
AB  - The authors, on the basis of their recent experiences in treating biliary ileus,
      discuss diagnostic problems of serious side effects and talk about more recent
      diagnostic techniques. Above all ecography, CT, and Endoscopic Retrograde
      Cholangiography are able to offer, in a lot of cases, a correct preoperative
      diagnosis. Endoscopic Retrograde Cholangiography is a real progress even if it
      needs a more extensive use and, presents some doubts about its utility like all
      diagnostic techniques in biliary ileus.

PMID- 8992388
TI  - [Invaginated bronchoplasty: wedge resection and sleeve reconstruction].
AB  - The purpose of this report is to illustrate a bronchoplastic technique in upper
      right lobectomy which is equivalent to sleeve resection but allows to preserve
      the unaffected portion of the bronchial wall. The technique consists in the
      resection of the infiltrated bronchial wall, sparing the unaffected part The
      distal bronchial stump is then invaginated into the stem bronchus in such a way
      that the anastomosis line is located at the highest possible level, ideally where
      it would be carried out if standard sleeve resection would be performed. The
      anastomosis is accomplished by U-Shaped, 3-0 vicryl sutures. The major advantage
      of this procedure is probably due to the preservation of the systemic artery
      bronchial supply to the distal stump passing through the unaffected bronchial
      wall; the resulting more vital distal stump may reduce incidence of suture line
      healing problems.

PMID- 8992387
TI  - [Surgical treatment of inguinal hernia using a "tension-free" technique and local
      anesthesia. Initial experience].
AB  - Between January, 1991 and December, 1993, 208 subjects with monolateral and 19
      with bilateral inguinal hernia were submitted to herniorrhaphy. Thirty-four were
      recurrent hernias. All but one bilateral hernias were treated at the same time.
      Eight cases were operated in emergency condition for acute strangulated hernia.
      Two-hundred and ten operations were performed under local, 17 under general and 1
      under spinal anesthesia. Herniorrhaphy was performed in 14 cases with the Bassini
      and in 38 with the Shouldice technique. In 191 instances the "tension-free" and
      in 3 the "plug" techniques were adopted utilizing a polypropylene mesh. Following
      local anesthesia 13 episodes of bradycardia with hypotension were recorded during
      the operation and 4 in the early postop period. There were no general
      complications. Two elderly patients developed urinary retention following general
      anesthesia. Local complications included 6 (2.4%) cases of infection and 4 (1.6%)
      cases of hematoma of the wound, and 5 (2.0%) cases of edema with infiltration of
      the cord. Percentage of follow-up at 1, 2 and 3 years was 96, 95, and 93 percent
      respectively. Five recurrences were recorded: in 1 case following Bassini repair
      (7.6%), in 2 following Shouldice (5.6%), and in 2 following tension-free (1.5%).
      Local anesthesia has been confirmed to be well accepted by the patients,
      effective an safe, especially in the elderly patients with high operative risk.
      Similarly, the tension-free hernioplasty has been confirmed as a simple, easily
      reproducible technique, followed by less pain and disability as compared with
      other types of herniorrhaphies, and more effective mainly in the treatment of
      recurrent hernia.

PMID- 8992389
TI  - [Surgical staging of pulmonary carcinoma. Probability of error].
AB  - 234 patients with lung cancer and operated in Thoracic and Cardiovascular Surgery
      Department of Careggi Hospital in Florence have been evaluated in order to
      examine surgical staging accuracy in comparison with pathological staging. There
      is a statistically significative difference between surgical and pathological
      staging as a datum point. Surgeon is inclined to over-estimate the lymph-nodes
      involvement and the primitive tumor extension. It is important to bear in mind
      this bent whenever decisions of surgical strategy have to be taken.

PMID- 8992390
TI  - [Long-term central venous access in oncology. Review of a caseload of 750 cases].
AB  - Totally implantable central venous accesses systems are presently widely used in
      cancer patients. Perioperative and long-term morbidity of 750 consecutive
      implants performed from 1985 to 1994 were retrospectively reviewed. Our Series
      consisted in 616 (82.1%). Ports and 134 (17.9%) external tunnelled catheters with
      subcutaneous Dacron cuff (Hickmann or similar catheters) implanted by
      percutaneous access route in local anesthesia. Subclavian vein was the elective
      access route in 700 (93.3%) patients while in the remaining 50 (6.7%) the access
      was performed in the femoral vein, due to peculiar clinical conditions. One-day
      surgery was only required for 19 (2.6%) patients while outpatient surgery was the
      routine in 731 (97.4%) patients. Perioperative morbidity was at all similar both
      for Port and external catheters Series (p > 0.07). Late morbidity requiring the
      removal of the device occurred in 27/134 patients (18.7%) and in 40/616 (6.5%)
      for external catheters and Port Series, respectively (p < 0.002). The rate of
      infection, 2.3% for ports (p < 0.002). Patient's compliance was higher for Ports
      compared to external catheters. Apart from peculiar clinical conditions such as
      hematologic cancers, bone marrow transplantation or short life expectancy, Ports
      seem to guarantee for a lower morbidity coupled with better long-term results.

PMID- 8992391
TI  - [Colorectal obstruction caused by cancer].
AB  - The authors report their experience, matured in 10 years, in the management of
      cancer of the rectum and large bowel complicated by obstruction; 425 patients out
      of 493 total cases of colorectal cancer presented an intestinal obstruction and
      underwent emergency surgery. In 386 cases it was possible to perform resection
      (91%). The surgical treatment of the patients with right colon obstruction
      usually consisted of a right hemicolectomy. The surgical treatment of left colon
      obstruction is still controversial; in the experience of the authors it was
      accomplished by Hartmann operation mainly until 1985; in recent years the authors
      have introduced a procedure of intraoperative anterograde irrigation of the colon
      and they have performed resection-anastomosis in a single stage successfully but
      only in selected patients. In 4 out of twelve cases of cancer of the splenic
      flexure a subtotal colectomy was performed with one stage ileo-sigmoid
      anastomosis crowned with success. The authors examine the operative and
      postoperative mortality of the patients with colorectal cancer and point out that
      5 years survival is worse in patients with colorectal obstruction compared to
      elective operations (24% versus 41%).

PMID- 8992392
TI  - [Day hospital surgery. Our experience].

PMID- 8992393
TI  - [Experimental study of postoperative lavage: standardization of the method].
AB  - Postoperative infections are an outstanding problem in a surgical department. We
      have been studying them from a clinical and experimental point of view has a long
      time. In this study we present a method standardisation of postoperative
      peritoneal lavage as prevention of surgical infections. Winstar mice, infected
      with intra peritoneal E. coli cultures, underwent peritoneal lavage with saline
      solution or sterile water. The results showed the right amount of solution and
      the exact administration of lavage according to grade of infection. Encouraged by
      this result we are going to test the efficacy of anti microbial agents for the
      postoperative peritoneal lavage.

PMID- 8992394
TI  - [Prognostic significance of postoperative septic complications in surgery of
      rectal carcinoma].
AB  - AIM: To assess whether there is a correlation between the onset of postoperative
      sepsis and the 5-years survival rate in patients undergoing surgery for rectal
      cancer. EXPERIMENTAL DESIGN: A retrospective study of all patients, undergoing
      rectal cancer surgery during the period January 1981-December 1987. PLACE:
      General Surgery Unit, Hospital Arnau de Vilanova. PATIENTS: All patients operated
      with Duke's stage B and C colorectal neoplasms, excluding cases with
      postoperative complications not directly correlated to surgery: pneumonia,
      thromboblebitis, urinary infection or fever of unknown origin. FINDINGS:
      Postsurgical complications distinguished as minor (wall abscess) or major
      (anastomotic dehiscence, peritoneal abscess). 5-year survival rate. RESULTS: The
      actuarial 5-year survival rate of patients with major septic complications was
      significantly lower (p < 0.05) than that in noncomplicated cases. No difference
      was observed in the survival of patients with and without minor septic
      complications. CONCLUSION: Major septic complications secondary to colorectal
      surgery are still a threat in spite of improved techniques and antibiotic
      prophylaxis, and negatively influence the long-term survival rate.

PMID- 8992395
TI  - [Method and application limitations of decision support systems in acute
      pancreatitis].
AB  - Several decision support systems (DSSs) for acute pancreatitis (AP) were analyzed
      with reference to development methods, procedure limits and operational
      performances. Almost all the DSSs have been addressed to the early definition of
      severity, which appears the only decisional point in the approach to the
      management of AP. None of the three groups of methods, multifactor, scoring and
      bayesian systems, provides an explicit evidence of effectiveness. The multifactor
      systems (Ranson and successive) show inadequacy of design and operational limits
      which involve poor reliability and conflicting indications from the different
      centers. The scoring systems (APACHE, SAPS) have been projected and developed for
      clinical situations quite different from the AP at the onset, and seem more
      properly to be applicable to the monitoring of its complications. The bayesian
      systems, although the models used until now present important methodological
      shortcomings, are those which furnished the best results but are lacking in
      clinical validation and present a form hardly accepted by the clinician. Despite
      the disappointing operative results and their limited use in the AP, the DSSs
      probably constitute one of the most effective tools to improve the management of
      the severe forms, on condition that the methodology of design enad trial is
      correctly adjusted.

PMID- 8992396
TI  - [Update on deep thrombophlebitis and pulmonary thromboembolism].
AB  - Pulmonary thromboembolism, a frequent complication in deep vein thrombosis, is
      still a pathology with a high rate of mortality and morbidity. The authors
      underline that this pathology is particularly frequent after some types of
      surgery and in subjects with primary or secondary risk factors. The paper
      analysis the pathogenesis of deep-vein thrombosis and the physiopathology of
      pulmonary embolism. The authors then outline the current management in terms of
      the diagnosis, prophylaxis, and medical and surgical therapy of this pathology.

PMID- 8992397
TI  - [Incidentally discovered masses: diagnostic and therapeutic features].
AB  - The term "incidentaloma", which was first used to indicate a mass discovered by
      chance at an adrenal level, is currently used to indicate any lesion identified
      accidentally, namely in the absence of specific symptomatology, during
      echographic or tomographic examination. The authors report their experience of
      just over one year and, through a review of the literature, draw attention to the
      fact that these incidentalomas raise unresolved problems both from a diagnostic
      and therapeutic point of view. They hope that routine abdominal echography will
      be extended at least to a selected hospital population given that these lesions,
      diagnosed by chance, may be malignant or even if benign may have a potential
      evolution. Obviously surgery in these cases would lead to a marked prognostic
      improvement.

PMID- 8992398
TI  - [A case of pancreatic somatostatinoma].
AB  - The authors describe a case of somatostatinoma localized in the body and tail of
      the pancreas. They emphasize the rarity of this finding (only 33 cases with
      certain pancreatic localization are reported in literature) and the absence of a
      distinctive syndrome, which could direct to an early diagnosis, the authors are
      in doubt about the real incidence of this disease. The absence, generally, of a
      distinctive syndrome, the poor condition of these patient and then the lack of
      surgical treatment and histological examination, could lead to a lower valuation.
      Delayed diagnosis and then the local extension of this neoplasm often make
      surgical treatment vain. Nevertheless since somatostatinoma has more
      possibilities of radical resection than pancreatic cancer, it's required to know
      its features and course so to increase possibilities of an early diagnosis. In
      fact disregarding surgical treatment, the survival of these patients, one year
      after diagnosis, is about 48%. This result is better than the survival of
      patients with pancreatic or biliary duct cancers. Current diagnostic procedures
      are reported.

PMID- 8992400
TI  - [Solitary fibrous tumor of the pleura. Clinical case].
AB  - Solitary fibrous tumors of the pleura represent a rare clinicopathological
      entity: 456 cases only have been reported since 1991. A interesting case of
      solitary fibrous tumor of the pleura is described here, because it turned up in a
      female patient followed up for a bilateral breast cancer and so with the exact
      determination of the period of beginning. The complex morphological picture is
      illustrated in relation to other cases reported in the literature.
      Immunohistochemical results are stressed, particularly as regards the
      coexpression of vimentin and desmin without necrosis and the low number of
      mitosis. As there are no criteria to determine the possible aggressive or
      malignant behaviour of the tumor, surgical resection of the lesion is
      indispensable both to resolve the diagnosis and to carry out the only proposable
      therapy.

PMID- 8992399
TI  - [General surgery after lung transplantation].
AB  - The authors report the case of correction of a large laparocele after lung
      transplant. Paradoxical respiration interfered with patient breathing. Three
      overlapping meshes were used to surgically correct the wound. Excellent results
      were achieved. Cortisone and immunosuppression therapy was not discontinued;
      infection risk was minimized by implementing rigorous asepsis and a wide spectrum
      antibiotic therapy.

PMID- 8992401
TI  - [Benign schwannoma of the hand. Considerations on a clinical case].
AB  - The authors here describe, both macroscopically and microscopically, the case of
      a cellular schwannoma on the hand of a 66 year old man. The tumor had been
      present asymptomatically for about forty years and macroscopic examination showed
      it be a softly teseturs fibroma and to have slight transversal mobility. The
      histologic examination revealed dense tissue formed by elongated cells, which
      tended towards a layered formation. The mitoses were exceptional. There were also
      areas scattered with a large number of random vacuolated cells. There were no
      particular difficulties during the excision, and one year after surgery there was
      no apparent change or relapse.

PMID- 8992402
TI  - [Metachronous intra-abdominal fibromatosis of the gastro-spleno-colonic ligament
      and the mesentery: histopathogenetic interpretation. Report of a case].
AB  - The paper reports a case of intra-abdominal fibromatosis with an initial
      localisation in the gastro-spleno-colic ligament followed by a metachronous
      localisation in the mesentery. Both localisations preceded the appearance of
      sigmoidorectal polyps and ovarian polycystosis. The authors discuss the
      biological problems related to the pathology and tend to interpret it as a dys
      reactive disease of connective tissue in a genetically predisposed, subject.

PMID- 8992403
TI  - [Neuroendocrine carcinoma of the skin].
AB  - Merkel cell carcinoma is an unusual neuroendocrine tumour that arises in the
      derm. The case reported seemed to deserve the author's attention because of the
      clinical features, pathological findings and natural history (local recurrence,
      regional lymph node metachronous metastases, distant metastases). The authors
      believe that a differential diagnosis between Merkel cell carcinoma and other
      tumours located in the subcutaneous tissue is mandatory, in order to perform
      specific immunohistochemical and ultrastructural study.

PMID- 8992404
TI  - [Cystic nephroma].
AB  - The authors describe a rare case of cystic nephroma treated by partial surgical
      excision. Because there is concurrence in the association of multilocular cysts
      with Wilms tumors and others tumors of the kidney, it is underlined the
      importance of a differential diagnosis to avoid nephrectomy for treatment of this
      benign neoplasm.

PMID- 8992405
TI  - [Short term changes in risk factors of cerebrovascular diseases. A failure of
      preventive measures?].
AB  - BACKGROUND AND PURPOSE: Stroke is the third main cause of death in western
      countries. To evaluate its ever-changing characteristics and the impact of recent
      public campaigns on cardiovascular risk factors (CRFs) in stroke morbidity and
      mortality, we carried out a retrospective investigation on subjects with
      cerebrovascular disease in different periods. METHODS: All clinical data of
      patients with acute cerebrovascular disease (TIA or stroke) admitted to a
      regional hospital (Padua, Italy) during two distinct years (1985 and 1992) were
      examined (381 in 1985 and 440 in 1992). In every case the characteristics of the
      episode, clinical course, concomitant CRFs and relevant biochemical and
      instrumental examinations were recorded. RESULTS: Altogether Transient Ischemic
      Attack (TIA) represented almost half the records; remaining cases could be
      classified as ischemic stroke (66% vs 55%), Intracerebral Haemorrhage (17% vs
      26%) and subarachnoideal haemorrhage (17% vs 19%) (1985 vs 1992, respectively).
      The mean hospitalization period was longer in the most recent year, particularly
      in haemorrhagic patients (H-P, subarachnoid + intracerebral haemorrhage); the in
      hospital case fatality rate was reduced in HP while it was significantly
      increased in those with Cerebral Ischemia (CI-P, TIA + ischemic stroke). The
      prevalence of blood hypertension, atrial fibrillation and dyslipidaemias rose
      significantly in 1992 compared to 1985. High plasma lipids were more frequently
      present in CI-P than in H-P; their 7-year increase was particularly related to
      combined forms, rather then isolated hypercholesterolemia or
      hypertriglyceridemia. CONCLUSIONS: These results do not agree with an
      hypothetical improvement in the prognosis of stroke in the period we considered.
      Besides the efforts aiming at reducing CRFs in the short term have not shown to
      be successful.

PMID- 8992406
TI  - [Transmembrane sodium transport systems in various forms of
      hyperlipoproteinemia].
AB  - The possible interrelationships between the erythrocytic transport systems of Na+
      (Na+/K+ pump, Na+/K+ cotransport, Na+/Li+ countertransport, Na+ passive
      permeability) and the plasmatic lipids (cholesterol, triglycerides, HDL, LDL,
      apoprotein A1, apoprotein B) were studied in 42 normotensive subjects with
      different forms of hyperlipoproteinaemia and with a negative familiarity for
      arterial hypertension. In subjects with hypercholesterolaemia
      (hyperlipoproteinaemia II A and II B) an elevated activity of the Na+/K+ pump was
      noticed, while in subjects with hypertriglyceridaemia (type IV) an increase in
      Na+ passive permeability and Na+/Li+ countertransport with a lower level of
      intraerythrocytic Na+ was shown. A negative correlation was observed between the
      total efflux of Na+ and Na+/K+ pump and the levels of cholesterol (r = -0.43, p <
      0.04 and r = -0.41, p < 0.05) and the apoprotein B/A ratio (r = 0.42, p < 0.05
      and r = -0.50, p < 0.01). A negative correlation was also noticed between the
      Na+/K+ pump and the levels of apoprotein B (r = -0.41, p < 0.05). The Na+/K+
      cotransport appeared inversely correlated with the levels of HDL cholesterol (r =
      -0.42, p < 0.05), while the Na+ passive permeability was negatively correlated
      with the levels of LDL (r = -0.43, p < 0.04) and positively correlated with the
      plasmatic triglycerides (r = +0.54, p < 0.01). Such data show that the plasmatic
      lipids can influence the systems of transmembrane ionic transport of Na+ and play
      an important role also this way, in cardiovascular pathology.

PMID- 8992408
TI  - [Difficult digestive hemorrhage: angiodysplasia].
AB  - The authors report 7 cases of ileal and colonic angiodysplasia observed over a 3
      year period (1992-1994). After a review of literature concerning etiology,
      pathology, diagnosis, and treatment emphasize the use of angiography for
      preoperatory diagnosis an intraoperatory localization of the lesion when this one
      is localized in the ileum. After review of usefull therapies, they stress the
      role of surgery as the most used therapy and only really complete.

PMID- 8992409
TI  - [Rendu-Osler-Weber disease. Report of a clinical case].
AB  - Rendu-Osler-Weber disease is an hereditary disorder characterized by cutaneo
      mucous telangiectasis and vascular abnormalities in several organs. Bleeding,
      especially epistaxis, represents the most important clinical feature. Pulmonary
      arteriovenous fistulae can cause hypoxaemia, haemoptysis, polycythaemia and
      clubbing. Diagnosis is based on family and personal history, teleangiectasis,
      laboratory (haemochrome, fibrinogen, PT, PTT) and instrumental findings
      (endoscopy and/or roentgen). Therapy depends on symptoms. Embolization of
      pulmonary arteriovenous fistulae and laser treatment of intestinal vascular
      abnormalities have been successful. Danazol treatment yielded controversial
      results. We report the case of a patient admitted for arterial hypertension and
      recurrent epistaxis. Rendu-Osler-Weber disease diagnosis was made based on
      positivity at family and personal history, clinical examination, laboratory and
      instrumental findings. In conclusion we underline the pivotal role of anamnesis
      and clinical examination in the differential diagnosis of hereditary bleeding
      disorders and emphasize the importance of early diagnosis for the correct
      therapeutic approach.

PMID- 8992407
TI  - [Circadian patterns of ischemic events].
AB  - These is evidence of circadian variations in the occurrence of ischemic events
      such as: silent myocardial ischemia, stable angina, instable angina, acute
      myocardial infarction, sustained ventricular tachycardia, cerebral infarction,
      transient ischemic attack (TIA) and sudden cardiac death. In the general
      population many cardiovascular disorders occur with the greatest frequency
      between 6 and 12 a.m. (i.e. after awakening). Blood pressure, too, follows a
      distinct circadian pattern. Factors affecting circadian variations in
      cardiovascular disorders include physiological determinants, such as heart rate,
      catecholamine release, and platelet aggregation-which themselves cyclically vary
      , and exogenous factors such as mental stress, anxiety, and physical activity. In
      chronotherapy, circadian variations in disease states and in the pharmacodynamic
      properties of drugs are exploited to improve prevention and treatment.
      Characterization of diseases states with this approach allows more accurate
      determination of the times when patients are at highest risk and therefore in
      greatest need of preventive measures; it also provides a mechanism for designing
      optimal drug regimens. In this review we therefore describe recent findings about
      the effects of biorhythms on cardiovascular disorders and their implications for
      optimal drug therapy.

PMID- 8992410
TI  - [Unusual case of acute suppurative thyroiditis].
AB  - Acute suppurative thyroiditis is an acute disease of the thyroid gland. In this
      paper the authors report a case of acute suppurative thyroiditis complicated by
      abscessual evolution in an addict patient study with ultra-sonography and treated
      with fine needle aspiration and antibiotic therapy. The patient reached our
      observation for a swelling of the neck. Ultrasonography showed diffuse
      hypoechogenicity in both thyroid lobes and mixed nodule with hyperechoic
      trabeculas inside. This nodule underwent fine needle aspiration (FNA) for
      cytologic and cultural evaluation. Diagnosis was acute suppurative thyroiditis.
      Ultrasonography presented features similar to other thyroid pathology (sub-acute
      thyroiditis, haemorrhagic cyst, thyroid lymphoma and anaplastic carcinoma). In
      our case none of the ultrasonographic features were diagnostic except hyperechoic
      trabeculas inside. Ultrasonographic features of acute suppurative thyroiditis are
      very rare in the literature. Ultrasonography and fine needle aspiration are the
      only methods that confirm this diagnosis.

PMID- 8992411
TI  - [Effectiveness of and tolerance to ceftibuten in the treatment of chronic
      bacterial bronchitis exacerbations in an elderly population].
AB  - 117 patients suffering for bacterial exacerbation of chronic bronchitis were
      treated with ceftibuten, a new orally administered cephalosporin, at the dosage
      of 400 mg once a day for 7.9 days (range 5-14). The results, referring to 105
      evaluable patients, underlyne ceftibutent's efficacy (good clinical results in
      96.1% of 102 treated patients) and safety; before and after treatment values of
      spirometric tests were notable in terms of improvement of lung functions.

PMID- 8992412
TI  - [Evaluation of an immunoenzymatic method for determining the tumor marker CA 15
      3)].
AB  - CA 15-3 determination has graved to be of clinical utility for diagnosis,
      evaluation and monitoring patients suffering from tumor. The aim of our study was
      to compare Sorin (kit ETI CA 15-3 K) and BMI (Enzymun-test CA 15.3) screening
      between two methodologies' capability. The results obtained were evaluated by
      using a Passing and Bablok correlation, Spearman rank correlation coefficient.
      The results obtained shown an over-valuation of the Sorin method vs. BMI.

PMID- 8992413
TI  - [Evaluation of an immunoenzymatic method to determine the tumor marker CA 125].
AB  - CA 125 determination has proved to be of clinical utility for diagnosis,
      evaluation and monitoring patients suffering from tumor. The aim of our study was
      to compare Sorin (kit ETI CA 125 K) and BMI (Enzymun-Test CA 125) screening
      between two methodologies' capability. The result obtained was evaluated by using
      a Passing and Bablok correlation, Spearman rank correlation coefficient. The
      results obtained show a low correlation between the two methods.

PMID- 8992414
TI  - [Magnetic fields in physical therapy. Experience in orthopedics and traumatology
      rehabilitation].
AB  - The present research is based on the premise that magnetic fields stimulate
      biological tissues, as many international works assert. They believe in the real
      aid of this therapeutical treatment in orthopedy and traumatology. The authors
      work in Rehabilitation Department of a traumatological hospital, so they have
      studied therapeutical results in ELF magnetotherapy on their patients for as long
      as six months.

PMID- 8992415
TI  - International Forum on Advanced Techniques in Lens and Cataract Research.
      Proceedings of the 7th Scheimpflug Club Meeting. Kanazawa, Japan, June 6-8, 1995.

PMID- 8992416
TI  - [Endocrinologic complications of neurofibromatosis type 1].
AB  - Neurofibromatosis type 1 is the most common autosomal dominant inheritable
      disease, which is often associated with secondary forms of hypertension and with
      tumors of neuroectodermal origin. The authors present the results of evaluation
      of 60 members of 3 families. Of the 60 family members, 13 subjects had symptoms
      of neurofibromatosis type 1 disease, of which 7 subjects were evaluated. The case
      histories of patients are discussed: (1) An incidentally discovered adrenal tumor
      was proved to be a pheochromocytoma. (2) Because of complaints similar to
      thyrotoxicosis, thyrostatic drugs were administered for years without effect and,
      finally, an adrenal phaeochromocytoma was diagnosed after the presence of
      neurofibromatosis was established. (3) Preeclamptic pregnancy of a young
      primigravida complicated with severe HELLP syndrome (hemolysis-elevated liver
      enzymes-low platelet count) led to thorough evaluation which revealed renal
      artery stenosis. In this patient, percutaneous renal artery angioplasty resulted
      in a complete cessation of hypertension. (4) Glucocortocoid replacement therapy
      in a patient with neurofibromatosis type 1 resulted in a complete normalization
      of both secondary adrenal insufficiency and a previously unexplained iron
      refractor iron-deficient anemia. The case histories of the patients demonstrate a
      lack of in-depth knowledge of neurofibromatosis in clinical practice. A regular
      follow-up of neurofibromatosis patients is suggested in specialized health
      centers.

PMID- 8992417
TI  - [Fiberoptic bronchoscopy in intensive care units].
AB  - The authors have retrospectively analysed 161 bedside fiberoptic bronchoscopies
      performed at intensive care units and demonstrate its' main indications, results
      and influences on the patients' condition. In 35.4% of cases immediate
      improvement was observed, in 31.6% the examination contributed to choose the
      proper treatment. Due to the safe method only one serious complication occurred
      because of bronchoscopy. The results justify-according to the literature-that
      fiberoptic bronchoscopy is an indispensable method to check airways and for
      diagnostical and therapeutic interventions of critically ill patients.

PMID- 8992418
TI  - [The effect of blood transfusion on the late results of the surgical treatment of
      rectal cancer].
AB  - Prospectively recorded data of 149 patients undergoing curative resection for
      rectal cancer between 1985-1992 were evaluated. Survival rate and tumor
      recurrence were studied in transfused and non-transfused groups of patients.
      There wasn't statistically significant difference found between the two groups
      concerning the 5 year survival rate (53 and 59%). Whole blood had more
      deleterious effect on survival than packed red cells (48 versus 61%), but the
      difference didn't reach the statistical significance level. The 5 year survival
      rate of patients without transfusion was significantly higher (p < 0.05) than
      those received > 800 ml of blood (59 v.s. 33%). The tumor recurrence wasn't
      associated with transfusion. Neither the quality, nor the amount of blood seems
      to influence on the recurrence rate significantly. In the group of patients with
      > 800 ml of transfusion the lower preoperative hematocrit, the higher rate of
      abdominoperineal resection of the rectum and the longer duration of surgery than
      those of patients nontransfused reflect the unfavorable tumor stage and the
      difficulties in removing the tumor. Authors believe these circumstances
      necessitating the transfusion may be responsible for worse outcome of rectal
      cancer but the immunosuppressive effect of the blood can't be excluded.
      CONCLUSIONS: stricter indication than earlier is necessary for administration of
      blood transfusion to patients with rectal cancer to decrease the risk of
      transfusion-transmitted infections and to avoid the possible immunosuppressive
      effect of the blood. Packed red cells is preferable. Decreasing volume of
      perioperative homologous transfusion by improving surgical technique and clinical
      application of autologous transfusion should be considered.

PMID- 8992419
TI  - [Nitric oxide. Basic research and possible clinical use].
AB  - The journal Science considered nitric oxide (NO) the molecule of the year 1992.
      This small, instable, potentially toxic gas freely crosses cell membranes. NO is
      produced from L-arginine by NO-synthase. The various physiological and
      pathological effects of NO can be explained by its reactivity and different
      routes of formation and metabolism. In mammals, at least three isoenzymes of NO
      synthase (neuronal, endothelial and inducible forms) are known. NO exerts
      different effects in acidic, neutral and basic pH conditions, it is cell
      protective when produced is small quantities whereas it is toxic when exceeds
      millimolar concentrations. Both the overproduction and suppression of NO release
      may have harmful effects. As a neurotransmitter, it plays important role in cell
      signaling, in the erection of penis and also in the learning process. When
      produced by endothelial cells, it is a potent vasodilatator, and phagocytes use
      NO to kill microorganisms. NO also may play pathological role in chronic
      inflammations, immune processes and tumour generation. Based an our current
      knowledge, NO can be used in the therapy of pulmonary hypertension, cerebral
      ischemia and relaxation disturbances of smooth muscle sphincters, and the
      blockade of NO synthase activity may help in the management of septic shock,
      hypotension and inflammations.

PMID- 8992420
TI  - [Septo-optic dysplasia (de Morsier syndrome)].
AB  - Authors report a rare central nervous system malformation on giving account of
      three of their cases. The possibility of septo-optic dysplasia should be raised
      in children with unilateral or bilateral hypoplasia of the optic nerve. The use
      of neuroimaging technics is necessary for establishing the diagnosis. Knowing the
      disease is important because of the hypopituitarism which can accompany it, and
      which can necessitate an early hormone replacement therapy.

PMID- 8992421
TI  - [Micro- and modern minilaparotomy in biliary tract surgery. (Remembering Janos
      Balassa)].
AB  - The author remembering "Janos Balassa" points out how his legacy can be used as a
      moulding energy for surgery in our present time. After analysing the personality
      and values of Balassa the results of 1357 consecutive unselected
      cholecyatectomies and choledocholithotomies performed in micro- and modern
      minilaparotomy are analyzed. The issue of mini laparotomy has not been defined
      yet, so that abdominal incisions from 3 to 10 cm are also called mini laparotomy.
      The author suggested in 1992 that the term microlaparotomy be applied to
      incisions less than 4 cm, modern mini laparotomy from 4 to 6 cm, and conventional
      mini laparotomy from 6 to 10 cm. In contrast to other mini laparotomies he uses a
      vertical incision in the infrasternal triangle. From the functional anatomical
      point of view this approach is advantageous because it is situated above Calot's
      Triangle and Moosman's area and results in reduced postoperative pain. Special
      lighting retractors have been developed for excellent exposure and illumination
      of the surgical field to make the operation safe. Micro and mini laparotomies can
      be used for both early and late reoperations on the biliary system and also for
      the conversion of laparoscopic cholecystectomy. At our department conventional,
      laparoscopic and micro laparotomy cholecystectomy are used. Considering both
      surgical and economic factors, the author has found that micro laparotomy
      cholecystectomy offers better results than conventional and laparoscopic
      cholecystectomy.

PMID- 8992422
TI  - [Primary and secondary ovarian tumors in patients with colorectal carcinoma.
      Thoughts on preventive oophorectomy].
AB  - The occurrence frequency of metastasis of colorectal carcinomas in ovary is 6
      percent. Such metastases greatly decrease patients chances for recovery. The
      authors found ovary tumors isolated or in metastatic state in 7 cases out of 56
      colorectal cancer patients of which in 6 cases led to patients' death. The
      authors review publications on prophylactic oophorectomy and summarize the
      indications of prophylactic oophorectomy.

PMID- 8992423
TI  - [Nail-patella syndrome: clinico-pathologic characteristics].
AB  - The nail-patella syndrome is a hereditary disorder showing an autosomal dominant
      trait. It is characterized by a series of skeletal disorders and nephropathy. The
      skeletal defects and the renal involvement might occur separately. The usual
      clinical presenting syndromes of the nephropathy are asymptomatic proteinuria,
      microscopic haematuria and sometimes nephrotic syndrome. In a considerable
      proportion of patients renal failure develops. We summarise the clinico
      pathological features of the disease presenting in two children and in a young
      man. The two children showed heavy microscopic occasionally, macroscopic
      haematuria, asymptomatic proteinuria and the adult patient had nephrotic
      syndrome. Nail-patella abnormalities were observed in one child without the
      involvement of family members. Except for the mother of the other child no urine
      abnormalities could be demonstrated in the patient's families. The kidney biopsy
      revealed the characteristic signs of the nail-patella syndrome in different
      extent: bundles of collagen fibrils in the glomerular basement membrane (GBM).
      Segmental and thinning of the GBM also occurred in the two children. This defect
      predisposes to the clinically dominant micro- and macroscopic haematuria. These
      children's reual function remained stable during the follow-up period of 4-7
      years. In the GBM of the third patient small subepithelial electron dense
      deposits-corresponding to stage I. membranous glomerulonephritis- and extensive
      collagen deposition was found. After two years follow-up persistent nephrotic
      syndrome and gradual decline in renal function could be observed.

PMID- 8992424
TI  - [In vivo effect of etoposide on the pharmacokinetics of methotrexate].
AB  - High dose (5 g/m2/24 h) methotrexate therapy was combined two times with
      etoposide (100 mg/m2/1h) infusions as a part of the Medulloblastoma protocol
      developed in our Department Vepesid therapy was administered in two different
      schedules. The first group of the patients have received etoposide immediately
      before and at the end (24th h) of methotrexate treatment. The second group was
      treated with etoposide at 24 h and at 48 hour after starting methotrexate
      infusion. In this latter group treatment related grade 3-4 toxicity developed
      more frequently than in the first group (58.6% vs 33.3%). The authors observed
      that after the second dose of etoposide given at 48 h (second group) both total
      and unbound serum methotrexate levels (determined by high performance liquid
      chromatography) were elevated by 53.14-109.19%, and 25.86-64.95%, respectively by
      the third hour after completion of Vepesid infusion. This effect was detectable
      for 6 hours. All the liver and kidney functions of the patients were in the
      normal range. These results suggest the possibility of partial recirculation of
      extra/intracellular methotrexate into the blood after etoposide administration.
      Based on these results the therapeutic protocol has been modified and Vepesid is
      given prior to and at the end (24 h) of high dose methotrexate treatment. Under
      these conditions only a slight decrease of methotrexate elimination has been
      detected between the 25-28th h. These results emphasize the role of possible
      schedule dependent interactions of cytostatic drugs.

PMID- 8992425
TI  - [Peripartum cardiomyopathy with fatal outcome].
AB  - The authors reported the case of a 26 year-old primipara who had unexplained
      congestive cardiac failure on the 9th week after delivery. There was no previous
      disease in her history however her pregnancy endangered because of imminent
      abortion was preceded by 1 artificial and 2 spontaneous abortions. In the acute
      phase she had to be resuscitated because of ventricular fibrillation and then she
      had a pulmonary embolism followed by pneumonia and therefore she was in septic
      state for 4 weeks. After a 4 month clinical remission she died unexpectedly at
      home. At autopsy the histological appearance of myocarditis, thymic hyperplasia
      and hypoplastic vascular system were observed.

PMID- 8992426
TI  - [After all, when was the first cardiac suturing performed?].

PMID- 8992427
TI  - [Support by telecommunication of decisions in diagnostic pathology. Experience
      with the first telepathology system in Hungary].
AB  - The term of telepathology can be determined as diagnostic work of the pathologist
      at distance via an interactive telecommunication connection in which the image of
      the specimen appears on a monitor instead of viewing it directly through a
      microscope. Being a part of the telemedicine, the fast development of the
      telepathology is based on the revolution of the new digital technology. Technical
      advances of telecommunication and of image procession in the latest 80s have
      provided the means to transfer huge amount of visual information in narrow
      communication bandwidth in two direction link. In 1995 multiple live image
      transmission with simultaneous voice transfer has been performed between the
      Department of Pathology of MI Central Hospital and 1.st Institute of Pathology
      and Experimental Cancer Research of Semmelweis Medical University, Budapest.
      Transfer rate via ISDN channel was 128 kbit/sec. The first live image
      telemedicine system in CCE/NIS countries has achieved transmission of cytological
      smears, frozen sections and paraffin embedded slides supplemented with
      immunohistochemical preparations. Quality of visual information using video
      conference software of standard H.320 was suitable for diagnosis. Development of
      global telepathology services depends on compatibility of different systems and
      on comprehensive examinations of cost, accessibility and quality for the clients
      and providers of telemedicine. Recent paper surveys shortly the historical
      development of the telepathology, analyses the essence of the new consultation
      technology, summaries the first experiences in Hungary and raises some questions
      have to be answered in the near future.

PMID- 8992428
TI  - [Current questions about estrogen receptor determination and hormone dependence
      (does estrogen receptor positivity equal estrogen dependence?)].
AB  - Exaggerated expectations were raised by estrogen and progesterone receptor
      determinations introduced in the 1970s for the estimation of hormone dependence.
      However only two thirds of estrogen and/or progesterone receptor positive cases
      respond to hormonal therapy. Radioligand binding immuno-assays, and
      immunohistochemical determinations are wide-spread, however not informative
      enough. The former two performed on tumor homogenate can not take into account
      the tissue composition, and heterogeneity of the tumor, and fail to detect
      receptors of the ligand-saturated forms, while the immunological methods do not
      give any functional information. There is increased evidence on the existence of
      dysfunctional estrogen receptor variants. One presents estrogen receptor negative
      progesterone receptor positive phenotype unable to bind its ligand but
      constitutively activates its specific DNA-sequence. The other most prevalent in
      estrogen receptor positive progesterone receptor negative tumors is a mutant
      "infertile" variant able to hamper normal function of the wild type estrogen
      receptor by heterodimerization. In order to better utilize estrogen, and
      progesterone receptor data, propositions are made as following: estrogen
      receptors from occasionally simultaneously performed biochemical and
      immunohistochemical determinations should be evaluated in context with other
      characteristics of the tumor; the detection of mutated defective estrogen
      receptors may suggest hormone resistance. The correct estimation of the
      prevalence or lack of hormone dependence is mandatory when systemic treatment
      especially in the adjuvant setting is becoming more and more individualized in
      breast cancer.

PMID- 8992430
TI  - [Significance of hyper-echogenic yolk sac in first-trimester screening for
      chromosome aneuploidy].
AB  - Recently, the measurement of the thickness and extent of the first-trimester
      posterior simple embryonic hygroma by vaginal ultrasound has become the most
      efficient method in the antenatal screening for chromosomal aneuploidies. The
      sensitivity of the screening is only 75-90%, therefore, the search for other
      potential (sonographic) markers is needed in order to increase the efficiency.
      Ultrasound measurement of the echogenicity and the diameter of yolk sac and the
      thickness of dorso-posterior simple embryonic hygroma was carried out in 3620
      first-trimester pregnancies between 9-11 weeks. A total of 105 embryos with
      simple hygroma of > or = 3 mm and 39 pregnancies with abnormal, hyperechogenic
      yolk sac of 1.8-4.0 mm in diameter were detected. Cytogenetic analysis through
      chorionic villi samples revealed chromosomal aneuploidies in 52 cases. In 19 of
      3620 pregnancies both hyperechogenic yolk sac and first trimester simple hygroma
      were present. Each of these 19 pregnancies were chromosomally abnormal.
      Hyperechogenic yolk sac alone was present in another 20 pregnancies with
      otherwise normal fetal findings. The authors could not accomplish sonographic
      identification of the yolk sac in 42 pregnancies. In conclusion, combined
      presence of hyperechogenic yolk sac plus first-trimester simple hygroma of 3 mm
      or more in the same pregnancy is highly associated with chromosomal aneuploidy
      between the 9-11 gestational weeks.

PMID- 8992429
TI  - [Octreotide in the prevention of hyperamylasemia following ERCP (a controlled
      multicenter study)].
AB  - The aim of the multicentric trial was to study the effect of octreotide
      (Sandostatin) on the rise of pancreatic amylase in the serum after ERCP based on
      a large number of patients. The study was carried out in a prospective random
      manner in 2102 patients in 11 endoscopic centers. Patients in the treated group
      received 0.1 mg octreotide acetate, and those of the nontreated (control) group
      received isotonic sodium-chloride subcutaneously before the ERCP and 45 minutes
      after. Serum amylase and blood sugar were checked before the endoscopic
      procedure, 6 and 24 hours later. Out of the total number of patients involved,
      data of 1199 patients (599 in the treated group, and 600 in the control group)
      were evaluated. Octreotide diminished the percentual increase of serum amylase
      levels following ERCP. However, the frequency of hyperamylasaemia was decreased
      only after in patients with chronic obstructive pancreatitis or in such patients
      after endoscopic sphincterotomy. The peak serum level of blood sugar was higher
      in the treated group compared to the controls. There was no difference in the
      clinical symptoms following ERCP between the two groups. CONCLUSION: the
      prophylactic use of long-acting somatostatin may diminish the frequency of
      hyperamylasemia after ERCP in patients with chronic obstructive pancreatitis or
      in those patients who subsequently underwent EST.

PMID- 8992431
TI  - [Multiple fibrous pseudotumor of the great omentum].
AB  - The authors describe a case of multiplex fibrous pseudotumor of the great omentum
      that developed in a 15 year-old man and was treated by surgical resection. They
      discuss the clinical and pathological differential diagnostic problems and give a
      review of the omental tumors and pseudotumors. The occurrence of pseudotumors in
      the abdomen is rare and these are mostly inflammatory variants. On our knowledge
      this case is one of the first of multiplex fibrous pseudotumor simulating fibroma
      that was localized in the great omentum.

PMID- 8992432
TI  - [Guido Baccelli (1832-1916), "renaissance man" in 19th century Italy].

PMID- 8992433
TI  - [In memory of Miklos Lambrecht, M.D].

PMID- 8992434
TI  - [Professionalism on the pretext of "scientometry"].

PMID- 8992435
TI  - [Clinical characteristics of Hungarian-type familial meningo-cerebrovascular
      amyloidosis].
AB  - Amyloid deposits of the CNS caused clinical symptoms in four members of a
      Hungarian family. Histological investigations revealed a systemic disease,
      immunohistologically the deposited material was a transthyretin variant, DNA
      analysis showed a new transthyretin mutation (TTRAsp 18Gly). The disease--named
      meningocerebrovascular amyloidosis, Hungarian type--is inherited dominantly like
      other already known familial amyloidoses caused by transthyretin variants,
      however it does not cause the usual familial polyneuropathy but symptoms similar
      to those of the rare oculoleptomeningeal amyloidosis. The aim of the present
      study is to point to differential diagnosis. Its complaints, neurological signs
      and clinical findings which may be suspect of atypical migraine, brain tumour,
      chronic leptomeningitis or herpes encephalitis, multiple sclerosis and Parkinson
      disease are analysed and compared with those of other known types of familial
      amyloidoses. Attention is drawn to symmetrical calcification on CT scans. Skin
      biopsy may help the diagnosis. At present, therapy is only symptomatic.

PMID- 8992437
TI  - [Management of severe orthostatic hypotension by head-up-tilt posture and
      administration of fludrocortisone].
AB  - A case of a 66-year-old man with recurrent episodes of syncope is reported. The
      syncopal attacks started five years ago in sitting and standing positions. At the
      time of admission the fainting attacks occurred 2-3 times per day. The diagnostic
      tests revealed severe orthostatic hypotension. The medical treatment was started
      with salt enriched diet and fludrocortisone. The efficacy of the therapy was
      tested by using the tilt table test with a self developed computer system
      consisting of a non-invasive finger blood pressure monitor and ECG. The
      orthostatic tolerance improved with the medical therapy, however remained
      unsatisfactory for the patient's daily activity. Though the patient had less
      frequent symptoms, he had still sustained episodes of recurrent syncopes. The
      medical therapy was than combined with sleeping in the 15 degrees head-up-tilt
      position. The repeat tilt table test was performed two weeks after initiation of
      the 15 degrees head-up-tilt sleeping. The orthostatic tolerance was markedly
      improved. The patient became free of symptoms and during a four-week follow-up
      his condition remained stable. At the control the patient reported about
      deterioration of his symptoms as a result of the discontinuation of sleeping in
      "head-up-tilt" position for two weeks. The objective signs leading to aggravate
      his symptoms was documented by the tilt table test. We reinstituted the "head-up
      tilt" sleeping in his therapeutic management.

PMID- 8992436
TI  - [Peri-conceptional multivitamin administration may result in higher frequency of
      twin pregnancies].
AB  - A randomized controlled trial of periconceptional multivitamin supplementation
      including 0.8 mg folic acid was carried out for at least 28 days before
      conception. The trial was continued until at least until the second missed
      menstrual period to test the effectiveness of this new primary preventive method
      in the reduction of neural tube defects. However, other pregnancy outcomes were
      also evaluated. Of total of 5,502 pregnant women, 4,846 births were analysed in
      the final data base. The rate of multiple births was significantly higher in the
      multivitamin group (3.8%) than in the placebo-like trace-element control group
      (2.7%), and in both groups exceeded the multiple birth rate of 2.2% of women in
      the Hungarian population at large. 7.3% of women in the multivitamin and 7.9% of
      women in the trace-element groups received ovarian stimulation treatment (mainly
      clomiphen) for hormonal dysfunctions, e.g. anovulation. Nonetheless, our study
      showed that periconceptional multivitamin supplementation, with or without
      stimulation, increases the rate of multiple births.

PMID- 8992438
TI  - [Experience with insertion of an endoscopic endoprosthesis in a case of
      inoperable bile duct calculi].
AB  - Endoscopic sphincterotomy for removal of stones from the common bile duct is an
      established procedure. Large stones, however, can be unavailable for basket
      trapping and/or extraction in some cases. In these patients, which are at high
      risk for surgery, endoscopic insertion of biliary endoprosthesis seems to be an
      alternative approach to dissolution therapy or ESWL. During the last 5 year,
      among 4081 ERCP-s 879 examinations demonstrated common bile duct (CBD) stones in
      our institutions. In 81 of these cases, an endoprosthesis was inserted into the
      CBD after extended endoscopic sphincterotomy because of failure of extraction of
      the large stones. Also ursodeoxycholic-acid treatment was initiated thereafter.
      Mean age of patients was 76 yrs (range 46-95 yrs), 51 females and 30 males. Acute
      complications after procedure were: mild bleeding not requiring transfusion, and
      1 perforation treated surgically some days after prosthesis placement. Late
      complications until now included: peritonitis in 1 case, and recurrent jaundice
      due to drain clogging in 12 patients. These patient were treated with replacement
      of endoprosthesis. Remaining patients are well since the procedure and in 26
      cases controlled about 17 months after endoprosthesis placement endoscopy
      verified significantly smaller or no stones in the common bile duct and in 4
      cases even the endoprosthesis has disappeared. CONCLUSION: endoscopic insertion
      of a biliary endoprosthesis is a safe and effective treatment for the huge CBD
      stones in high risk patients in whom endoscopic sphincterotomy and attempts to
      remove the stones are not successful. In more than 30% of cases dissolution of
      stones with ursodeoxycholic acid may be expected.

PMID- 8992440
TI  - Pennsylvania physicians can now share the risk.
AB  - Good news for Pennsylvania physicians: Early last month, the state announced
      major changes in policy toward integrated delivery systems (IDSs). This article
      summarizes the major regulatory changes which physicians considering involvement
      in any type of IDS need to know.

PMID- 8992439
TI  - [Fournier gangrene (manifestation of anogenital necrotizing fasciitis)].
AB  - In connection with a typical case, clinical features of genitaly extended
      Fournier gangrene--its pathogenic factors and the standpoints of treatment--are
      demonstrated. This infection of foudroyant nature, going on with significant
      mortality is held to be a characteristic form of necrotizing fasciitis,
      constituting main manifestation of toxic shock-like syndrome. Attention is drawn
      to the fact, that in case of internal diseases, predisposing factors respectively
      even by adequate therapy-outcome of the infection may be lethal nowadays as well.

PMID- 8992441
TI  - Surfing the web and parkinson's law.
AB  - The World Wide Web accounts for much of the popular interest in the Internet and
      offers a rich and variegated source of medical information. It's where you'll
      find online attractions ranging from "The Visible Human" to collections of lawyer
      jokes, as well as guides to clinical materials. Here's a basic introduction to
      the Web, its features, and its vocabulary.

PMID- 8992442
TI  - Physician burnout.
AB  - As managed care has disseminated throughout our health system, physicians have
      increasingly assumed the status of employees. The pressures associated with this
      cultural change, and the changes in medical practice style and pattern required
      by managed care employers, could result in a significant increase in the number
      of physicians experiencing burnout. This in turn could lead to a decrease in the
      quality and efficiency of the health care delivered by such organizations. In
      view of this, physician employers should become more aware of the problem and
      take appropriate preventive measures.

PMID- 8992443
TI  - Tuberculosis control through contact investigation.
AB  - With the resurgence of tuberculosis (TB) in the United States since 1984, much
      has been said of insuring proper treatment with modern therapy regimens and of
      patient compliance with medications. Yet, little has been said of the role of
      contact investigations associated with each case. TB control programs are
      uniquely prepared to perform these contact investigations. This article describes
      the contact investigations performed by a county TB program in one year to
      illustrate the effort involved.

PMID- 8992445
TI  - Fifth scope prompts reorganization.

PMID- 8992444
TI  - TB: will the past be prolonged?

PMID- 8992446
TI  - Who needs unnecessary stress? Basic steps prevent insurer audits.
AB  - To say the least, any type of audit or investigation can be very stressful on a
      physician's practice. And, of course, negative findings may lead to severe
      financial repercussions when an insurer demands refunds of overpayments, or you
      find yourself on the defensive in criminal or civil litigation. Although there
      can be no guarantees, taking the necessary steps now can prevent an audit and
      protect your practice if one does occur.

PMID- 8992447
TI  - Society opens door of change.

PMID- 8992448
TI  - Cystic fibrosis gene mutations detected in hereditary pancreatitis.
AB  - To determine the potential role of the Cystic Fibrosis Transmembrane Conductance
      Regulator (CFTR) gene in the etiology of Hereditary Pancreatits (HP), we analyzed
      this gene in two HP families. PCR-SSCP analysis was employed, followed by direct
      sequencing of DNA samples showing alterations by SSCP. A new alteration not yet
      detected in connection with CF was detected in one HP family. The alteration is
      in exon 7 and causes an amino acid change from Leu to Arg at position 327
      (L327R). L327R segregates with the disease within the family. We discovered
      another novel alteration (V1190P) in an HP patient of the second family. These
      results indicate that CFTR gene mutations may be involved in the etiology of HP
      and represent a challenge for further study of the role of (CTFR) in other
      digestive diseases.

PMID- 8992449
TI  - [Usefulness of spiral CT in the detection of hypovascular, well-differentiated
      hepatocellular carcinoma].
AB  - Whole liver scanning during artery-dominant phase using spiral CT was performed
      in 14 patients with 17 histologically proven well-differentiated HCCs, which were
      not depicted by hepatic digital subtraction angiography but by CT during arterial
      portography. The density of HCC relative to the liver was evaluated with
      conventional precontrast CT, spiral CT, and following conventional CT during the
      equilibrium phase. Comparison between spiral CT and magnetic resonance (MR)
      imaging of dynamic contrast studies was also investigated. Four tumors of 17 HCCs
      (24%) were shown as a high-density area by the artery-dominant phase using spiral
      CT. Consequently, the total sensitivity of these three kinds of CT techniques was
      elevated to 82%. The sensitivity of dynamic MR imaging was slightly greater than
      that of spiral CT. However, spiral CT sometimes made the diagnosis more
      conspicuous by it's good spatial resolution. Our results indicate that spiral CT
      has a potential benefit in the detection of hypovascular well-differentiated HCC,
      and MR imaging and spiral CT may be complement each other.

PMID- 8992450
TI  - [Detectability of simulated nodules on chest phantom by Fuji computed
      radiography: comparison of different nodule sizes, configurations and tube
      voltages].
AB  - The detectability of simulated nodules placed on a chest phantom and shown on FCR
      images has been studied. Different tube voltages (130 kVp, 100 kVp), presence or
      absence of compensation filter, various sites and different sizes (5 mm/10 mm)
      and configurations (spherical or broad based) of the nodule were examined. 112
      FCR chest phantom images were evaluated by ten radiology specialists utilizing
      ROC analysis. The detection rate for nodules was influenced in general by the
      site. The detection rate was as follows in decreasing order: intercostal,
      overlaid with one rib, two ribs, diaphragm and heart. Detection of nodules of 10
      mm in height was mainly influenced by the density of the lung where the nodule
      was located, whereas that of nodules of 5 mm in height was more dependent on the
      site of the nodule, probably greatly influenced by the amount of structure
      mottle. Spherical nodules of 5 mm in height were more frequently recognized than
      the broad-based ones. High kVp (130 kVp) resulted in a higher detection rate for
      both sizes of nodules than low kVp (100 kVp). Detection of spherical nodules
      overlying the heart or diaphragm was improved with the use of a compensation
      filter.

PMID- 8992451
TI  - [Utility of bolus dynamic CT for the detection of hypervascular malignant hepatic
      tumors: mainly referring to the comparison with delayed phase contrast-enhanced
      CT].
AB  - In order to analyze the usefulness of dynamic contrast-enhanced CT, 84 patients
      who had hepatocellular carcinoma or suspected hypervascular metastases were
      studied with conventional incremental dynamic CT (CID-CT) or double helical CT
      (DH-CT). Delayed phase contrast-enhanced CT studies were consecutively performed
      in all patients. Thirty-six of 84 patients had malignant hepatic neoplasms; six
      had hepatocellular carcinoma and 30 had metastatic tumors. At first, the
      detectability of hepatic lesions was evaluated with bolus dynamic CT and delayed
      phase CT. Dynamic CT has detected more lesions than delayed CT. Some hepatic
      lesions described as isodensity were missed on CID-CT. Therefore, delayed phase
      CT cannot be eliminated when CID-CT is performed. Secondly, hepatic lesion
      detectability with CID-CT was compared with that of DH-CT. DH-CT did not miss the
      hepatic lesions picked up by delayed phase CT and was expected to provide
      excellent detectability of hypervascular hepatic neoplasms. In addition, first
      helical CT showed most hepatic lesions as areas of obvious hyperdensity, while
      CID-CT did not show their correct vascularities. So-called hypervascular hepatic
      tumors, however, were not always hypervascular and were demonstrated as areas of
      iso-hypodensity even on initial helical scanning. Second helical CT was useful to
      detect these so-called hypervascular, but actually hypovascular lesions. In
      conclusion, dynamic CT was helpful in detecting hypervascular hepatic malignant
      neoplasms, and DH-CT was more accurate than CID-CT for the detection of hepatic
      lesions and the evaluation of vascular lesion.

PMID- 8992452
TI  - [Screening CT of the lungs: image quality compared with conventional CT].
AB  - More sensitive imaging methods may be required in the screening of early
      peripheral lung cancer. Among new radiologic techniques, helical volumetric
      computed tomography (CT) seems to be attractive. The image quality of helical CT
      with single breath-hold and low-dose technique (screening CT) was compared with
      conventional sequential CT in 12 patients to detect the pulmonary metastases. The
      screening CT protocol consisted of a 20 mm/sec table feed during a 20-second
      breath-hold at 40 mA, with reconstruction of images at 10 mm intervals.
      Conventional CT was performed with a 1-second scan time, 200 mA, and contiguous
      10 mm-thick sections. In the evaluation of mediastinal vessels, bronchi and
      pulmonary nodules, screening CT showed high detectability images comparable to
      conventional CT. But subsegmental bronchi or small nodules overlapping pulmonary
      vessels were more difficult to visualize by screening CT because of image noise.
      The authors conclude that although further improvement is necessary, screening CT
      of the lung is an attractive new application of CT.

PMID- 8992453
TI  - [Percutaneous CT guided bone biopsy in patients with suspected bone neoplasm].
AB  - Bone biopsy is necessary for the diagnosis of ambiguous skeletal lesions.
      Although several merits of computed tomography (CT)-guided percutaneous needle
      biopsy have been documented, few radiologists have performed this procedure in
      Japan. We performed this procedure with a newly introduced bone biopsy needle
      (OSTYCUT, angiomed, Karlsruhe, Germany) under CT guidance and evaluated the
      results. CT-guided bone biopsy (pelvic[n = 11]vertebral[n = 10], femoral[n = 1],
      sternal[n = 1]) was performed in 19 consecutive patients. Seventeen patients were
      suspected metastatic disease, and the others were suspected primary bone tumor.
      All biopsies but one were diagnostic. Malignancy was proved in 11 lesions. Three
      patients with prostatic carcinoma were proved to show no malignancy of bone
      lesions after a series of hormonal and chemotherapies. In one patient with both
      malignant mesothelioma and cervical carcinoma, the biopsy specimen from thoracic
      vertebra proved metastasis from mesothelioma. CT-guided bone biopsy is useful to
      evaluate the presence of malignancy and the effect of therapy for it, and to
      determine the primary site.

PMID- 8992454
TI  - [Proton magnetic resonance spectroscopy of excised pig liver].
AB  - After evaluating ex vivo pig liver by 1H magnetic resonance spectroscopy (1H-MRS)
      using a 1.5 Tesla super-conducting unit, the assignment of peaks was reevaluated
      in vitro using a 9.4 Tesla superconducting unit. The portal vein was cannulated
      and perfused by cooled Euro-Collins solution, and pig liver was removed and
      preserved in the solution. Five to 8 g of the liver was excised before and after
      preservation, then extracted by perchloric acid (PCA). In 1H-MRS of PCA extracted
      pig liver, large peaks of fatty acid disappeared, while peaks of the choline
      group from 3.2-3.3 ppm were clearly observed. Using high performance liquid
      chromatography (HPLC) and 31P (phosphorus)-MRS, the 3.23 ppm peak was determined
      as glycerophosphorylcholine (GPC), which diminished after preservation. The
      chronological change of GPC in PCA extracted pig liver was able to be observed by
      1H-MRS. GPC peak may play a role as an indicator in evaluating preserved liver by
      1H-MRS.

PMID- 8992455
TI  - [The long-term results of the irradiation therapy for the dural arteriovenous
      malformation].
AB  - Although radiotherapy has been used to treat non-neoplastic vascular diseases, it
      is not widely accepted as a standardized treatment for dural arteriovenous
      malformations (DAVM). The uncertainties regarding the therapeutic outcome and the
      benign nature of DAVM are the major factors that limit the indication of
      radiotherapy. In an attempt to assess the long-term benefits and risks of the
      treatment, we analyzed 24 patients with DAVM treated with radiotherapy. The
      cavernous sinuses were involved in 12 and the transversesigmoid sinuses in 12.
      Doses ranging from 10 to 56 Gy (median 44.9 Gy) were delivered by multiple
      fractionation. In terms of clinical improvement, complete response was achieved
      in 19 patients and partial response in five. Four patients had recurrence of
      symptoms; two patients were reirradiated with the result of good symptomatic
      relief, one patient was successfully treated with transarterial embolization and
      the other patient with less disabling symptoms was managed conservatively. No
      adverse side effects attributed to radiation were encountered during the follow
      up period of 0.5-17 years (median 8.5 years). Radiotherapy is a safe and
      effective method for the treatment of DAVM and is warranted in patients who are
      unsuitable for transarterial embolization or surgical procedure.

PMID- 8992456
TI  - [Evaluation of ultrasound hyperthermia system with a phantom model].
AB  - Ultrasound (US) hyperthermia is a local heating method that has recently been
      introduced into clinical practice. A prototype and modified version of this
      system using a phantom model (agar with bone inserted) were evaluated. The
      prototype system consists of a power delivery unit (0.5 MHz frequency) with a
      circulating cooled water bolus. This system heats a shallow area irrespective of
      power output, but has a tendency to overheat the phantom surface. We incorporated
      three modifications into the prototype. The modified type has three frequency
      applicators (0.5, 1.0, 1.5MHz) and a secondary bolus. Aluminum-urethane shields
      were used to cover the phantom surface located over bone preventing overheating
      of bone. By changing the applicator's US frequency, we could change the depth of
      the heating area. Overheating of the phantom surface and bone thus was avoided.
      These results suggest that our modified US hyperthermia system with multiple
      frequency applicators, a secondary bolus and aluminum-urethane shields provided a
      good heating pattern.

PMID- 8992457
TI  - [Clinical evaluation of ultrasound hyperthermia system].
AB  - We studied clinically ultrasound (US) hyperthermia system developed in Japan. The
      prototype system consists of a power delivery unit (0.5MHz frequency) and a
      coolded water bolus. The modified type has three frequency applicators (0.5, 1.0,
      1.5MHz) with a secondary bolus. Thirty-four patients with recurrent or metastatic
      tumors located in the shallow tissues were treated. Fourteen patients (Group I)
      were treated with the prototype system and 20 patients (Group II) with the
      modified type. In 13 of the Group II patients, aluminum-urethane shields were
      used to protect nearby bone from overheating. The heating goal was 42.0 degrees C
      for at least 30 minutes in the tumor's center. The temperature was raised to 42.0
      degrees C in 7 of 14 cases (50%) and in 17 of 41 sessions (41.5%) in Group I. In
      Group II the temperature was raised in 19 of 20 cases (95.0%) and in 67 of 80
      sessions (83.7%). Response rates were 50.0% and 75.0% respectively in Groups I
      and II. The incidence of side effects including burn and ostalgia were 100% and
      20% respectively in Groups I and II. These results suggest that the modified US
      hyperthermia system was valuable in clinical use.

PMID- 8992458
TI  - [Quantitative analysis of 99mTc-GSA liver scintigraphy with graphical plot
      method].
AB  - 99mTc-galactosyl human serum albumin (99mTc-GSA) is a newly developed receptor
      binding agent, specific for the asialoglycoprotein receptor, which resides
      exclusively on the plasma membrane of mammalian hepatocytes. Liver scintigraphy
      using 99mTc-GSA was performed on 65 patients with liver diseases. Dynamic data
      were obtained by gamma camera during 20 minutes after the intravenous injection
      of 3 mg (185 MBq) of 99mTc-GSA. The maximum removal rate of 99mTc-GSA (denoted as
      P(2)) was measured by two methods: nonlinear five-compartment model analysis
      adopting the Michaelis-Menten constant for the transfer of 99mTc-GSA from hepatic
      blood to receptor, and a graphical plot using compartmental dose curves. The
      graphical plot could estimate easily the maximum removal rate in terms of two
      data points of 0 and 1 minutes without nonlinear least squares and numerical
      integration. The results indicated that the maximum removal rate was decided
      immediately after the intravenous injection of 99mTc-GSA. Although 99mTc-GSA is
      recognized to accumulate nonlinearly on the liver, the rate constant P(2)*(1/min)
      of transfer from hepatic blood to the receptor was estimated by graphical plot,
      assuming a linear five-compartment model. P(2)*Km, which was given by the product
      of the rate constant P(2)* and the Michaelis constant Km, was well correlated
      with P(2). Next, for 99mTc-GSA liver scintigraphy, we applied a Patlak plot that
      was applicable to the linear system, and the rate constant Ku of transfer from
      extrahepatic blood to the liver was estimated. From the results of graphical
      plot, it was theoretically shown that Ku represented P(2). This was confirmed by
      clinical data.

PMID- 8992459
TI  - [Lumbar MR myelography in the prone position: evaluation of nerve root sleeve
      delineation].
AB  - Although MR myelography is able to depict the subarachnoid space noninvasively,
      its ability to depict the nerve root sleeve is poor. The authors placed subjects
      in the prone position to increase the volume of spinal-fluid within nerve root
      sleeves and improve their depiction in MRM. MRM images of five normal volunteers
      taken in the supine and prone positions were visually correlated. Improved
      delineation of nerve root sleeves was obtained in all subjects.

PMID- 8992460
TI  - [Blood flow measurement of portal vein with fast cine phase contrast MR imaging
      under breath-holding].
AB  - Flow measurements of the right portal vein were performed in seven healthy
      volunteers with the segmented k-space fast gradient-echo phase-contrast (fcard
      PC) sequence under breath-holding. The mean velocity and the flow rate of the
      right portal vein at maximal expiration, 14.3 +/- 4.4cm/sec and 457 +/- 218
      ml/min, were significantly greater (p < 0.01) than those at maximal inspiration:
      11.8 +/- 3.8cm/sec (mean +/- SD) and 364 +/- 191ml/min, respectively. Fcard-PC
      enabled flow measurements to be obtained under breath-holding. Using this
      technique, we demonstrated portal venous flow changes according to respiratory
      phase.

PMID- 8992461
TI  - [Preliminary study of radiological image transmission with B-ISDN].
AB  - We evaluated the utility of image transmission using broad band ISDN (B-ISDN).
      The B-ISDN network links Tohoku University Hospital (TUH), interfaced with CDDI,
      and Tohoku University Department of Technology, interfaced with FDDI (including
      Tohoku University Computer Center interfaced with Ethernet), at 10km distance
      interfaced to a Unix workstation. Voluminous radiographic images like MRI 3-D
      images of the pelvic organs digitized at 5-20 megabytes were transmitted at mean
      data rates of 1.03Mbps (CDDI-Ethernet) and 30.1Mbps (FDDI-CDDI) with no image
      distortion. Initially the image data are transmitted to the Computer Center &
      Department of Technology, then processed and relayed to TUH. B-ISDN can provide
      fast, accurate image transmission.

PMID- 8992462
TI  - [Rhyme and reason in osteoporosis treatment].

PMID- 8992463
TI  - [Osteoporosis--what can and should be done in Sweden 1996? Swedish Osteoporosis
      Society].
AB  - Very recently we have seen the advent of new approaches to the investigation,
      treatment and prevention of osteoporosis. Pending the results of large
      prospective studies, a Swedish panel of experts has attempted to appraise
      currently available scientific knowledge of osteoporosis and make
      recommendations. A summary of this appraisal includes advice on bone
      densitometry, and on the treatment and management of patients with suspected or
      verified osteoporosis. It is suggested that individually tailored physical
      activity should be a fundamental feature of prevention and treatment, and that
      women in the 50-70-year-old age group, and perhaps older women as well, should
      have a daily calcium intake of 1200 mg. Vitamin D supplementation is recommended
      for the elderly under institutional care who spend no time outdoors. Oestrogen
      replacement therapy should be considered as prophylaxis in women at greater risk
      e.g., due to manifest heredity, early menopause, low body weight, heavy smoking,
      or low bone mass, and in patients at risk of secondary osteoporosis.

PMID- 8992464
TI  - [Osteoporosis--what is being done in Norway 1996?].

PMID- 8992465
TI  - [Prevention with hip protectors. Biomechanical aspects in falls and hip
      fractures].
AB  - The cascade of events leading to hip fracture is: a fall, protective responses,
      impact to the hip, local energy absorption and bone strength. A fall from
      standing height on the hip corresponds to a force of about 3500 N and the bone
      strength of the proximal femur in elderly women and men ranges between 2000 to
      6000 N. Efficient hip protective systems have been developed and may be a
      significant factor in the prevention of hip fractures among the elderly with
      propensity to fall and osteoporosis. Theoretically, more than 90 per cent of all
      hip fractures can be prevented, and a substantial reduction in the rate of hip
      fractures can be obtained, when systematic intervention programs are initiated
      among nursing home residents. Prevention of hip fractures among home dwellers may
      be a greater challenge, although preliminary results seem promising. Improvement
      in design has made the protectors more compliant and may facilitate the aim of
      preventing hip fractures.

PMID- 8992466
TI  - [Diagnosis of minimal residual disease in autologous bone marrow
      transplantation].
AB  - ABMT (autologous bone marrow transplantation) is being increasingly used in the
      treatment of malignant diseases, including the acute leukaemias. Although ABMT
      seems to be superior to conventional chemotherapy in terms of disease-free
      survival, an unacceptably high frequency of relapse after ABMT remains a major
      problem. As such relapse may be due to malignant cells in the graft or residual
      malignant cells surviving in the patient after preconditioning therapy, it is
      essential to be able to detect and eradicate residual malignant cells. The
      article presents a review of available methods for the detection of minimal
      residual disease in conjunction with ABMT, especially regarding their relative
      sensitivity and specificity.

PMID- 8992468
TI  - [Patient complaints in Scandinavia].

PMID- 8992467
TI  - [Tetracyclines as anti-inflammatory treatment in skin diseases].
AB  - Tetracyclines are broad-spectrum bacteriostatic antimicrobials drugs,
      traditionally used in dermatology for the treatment of acne. Owing to their
      beneficial antiinflammatory properties, and the low risk and modest side effects
      associated with them, tetracyclines are also useful in treating several other
      skin diseases-either alone, or in combination regimens to reduce the intensity of
      the immunosuppressive effect.

PMID- 8992469
TI  - [Prevention of female genital mutilation in Sweden].
AB  - A three-year pilot study of female genital mutilation has been carried out at
      Gothenburg. There is increasing awareness of this issue, and discussions have
      started between immigrants and health-care professionals. By means of further
      information and education it is hoped to improve care of the victims, and in the
      long-term to eliminate a pernicious tradition. It is estimated that there are
      approximately 115 million victims of female genital mutilation in Africa alone.
      As a result of emigration, about 5000 young women from areas where it is
      practised are now to be found in Europe, and 16,000 in Sweden.

PMID- 8992470
TI  - [1st international conference on prioritization in health care].

PMID- 8992471
TI  - [Is a realistic discussion on prioritization in health care possible?].

PMID- 8992472
TI  - Interventions during transport.

PMID- 8992473
TI  - Index of suspicion. Case 2. Diagnosis: ulceroglandular tularemia.

PMID- 8992474
TI  - Index of suspicion. Case 3. Diagnosis: lupus nephritis.

PMID- 8992475
TI  - [Comparative genomic hybridization. A screening method in genetic tumor
      diagnosis].
AB  - Comparative genomic hybridization (CGH) is a new method of screening a tumor for
      genetic changes. The alterations are classified as DNA gains and losses and
      reveal a characteristic pattern that includes mutations at the chromosomal and
      subchromosomal levels. Although DNA from fresh-frozen tissue is recommended as
      the starting material, archival specimens can also be analyzed. Various examples
      are presented that illustrate the changes that occur in different tumor entities,
      and preneoplastic lesions, the differentiation of primary tumors from metastases,
      and the investigation of tumor cell lines that are resistant to cytostatic drugs.
      These examples emphasize that CGH can extend the possibilities for genetic
      diagnosis in tumor pathology.

PMID- 8992476
TI  - [Analysis program for quantitative detection of chromosome aberrations using
      comparative genomic hybridization].
AB  - Comparative genomic hybridization (CGH) is a molecular cytogenetic method for the
      detection of chromosomal imbalances between a tumor and a normal genome. In order
      to produce quantitative and reproducible results, we developed an image analysis
      program that allows the detection and mapping of the genetic alterations. The
      result is represented as a CGH sum karyogram in which the genetic changes are
      documented as color coded-chromosomes. The aim of our investigation is to
      correlate the genotype with the phenotype on the basis of CGH sum karyograms and
      thus to achieve a genetic characterization that will supplement the morphological
      tumor description.

PMID- 8992477
TI  - [Autonomy and malignancy of thyroid glad tumors. A critical analysis of the
      literature on the existence of hyperfunctioning follicular and papillary thyroid
      gland carcinomas].
AB  - Data in the literature communicated in 63 publications were evaluated in which
      scintigraphically warm or hot nodules were described as identical to a follicular
      or papillary carcinoma diagnosed based on histology of the resection specimen,
      thus suggesting autonomous hyperfunction of a malignant thyroid neoplasia. In the
      majority of cases, this assumption could not be accepted, or only within strict
      limits. In these patients, it appeared more likely that the carcinoma was located
      adjacent to or within a benign hyperfunctioning thyroid area or that large masses
      of a thyroid carcinoma had only simulated the picture of a hyperfunctioning
      nodule by suppression of endogenous TSH and thus of the residual parenchyma's
      function. In other cases, the diagnosis of a hyperfunctioning thyroid carcinoma
      had to be doubted or rejected owing to the lack of plausibility of the documented
      morphological findings. At the end of the literature survey, only 10 case
      descriptions unequivocally verified that, though very rarely, a papillary or
      follicular thyroid carcinoma may manifest itself as a solitary warm or hot
      thyroid nodule. Such a scintigraphical finding thus cannot be regarded as proof
      of benignancy of a given thyroid tumour.

PMID- 8992478
TI  - [Cell biology of osteoclasts and molecular mechanisms of bone resorption].
AB  - The maintenance of a normal skeletal shape and bone mass closely depends on a
      normal osteoclastic activity, as do bone growth and repair. Thus, the improvement
      of our means of therapeutic intervention will depend on our better understanding
      of the molecular basis of bone resorption and of the cellbiology of the
      osteoclast. This review-article presents our current opinion of the molecular
      mechanisms of bone resorption by the osteoclast. After describing the
      morphological features of the osteoclast, aspects as cell mobility, attachment,
      enzymesynthesis, transmembrane transport, osteoclast differentiation and
      function, as well as the protooncogenes c-src and c-cbl and their role for bone
      resorption are presented in detail.

PMID- 8992479
TI  - [Synopsis of unbalanced chromosome aberrations in neuroblastoma by comparative
      genomic hybridization].
AB  - Neuroblastoma is the most frequent extracranial solid tumor of early childhood.
      Histologically and genetically, neuroblastoma represents a heterogeneous group of
      tumors with significant differences in clinical behavior. In the past, several
      different characteristic chromosomal aberrations of neuroblastoma have been
      described, of which a deletion on chromosome 1p and N-myc amplification have been
      shown to be of major prognostic significance. However, the role of various other
      nonrandom DNA imbalances in tumor development and progression needs to be
      clarified. Taking advantage of the recently established comparative genomic
      hybridization (CGH), we show that this method is able to accurately detect
      chromosomal imbalances of known prognostic impact. As CGH gives a comprehensive
      picture of genetic imbalances in just one experiment, it additionally sheds light
      on other abnormalities of possible prognostic relevance. We therefore recommend
      further use of this method not only in the field of research but also for the
      purpose of genetic routine diagnostics in neuroblastoma.

PMID- 8992480
TI  - [Comparative DNA cytometric and cytogenetic ploidy determination of
      chondrosarcoma and osteosarcoma].
AB  - 10 chondrosarcomas and 10 osteosarcomas were examined using cytogenetics and DNA
      image-cytometry. Cytogenetically 6 of 10 chondrosarcomas and 4 of 10
      osteosarcomas showed hyperdiploid tumorcells. By DNA-cytometry in 8 of 10
      chondrosarcomas and 9 of 10 osteosarcomas hyperdiploid tumorcells resp.
      hyperdiploid stemlines were detected. This discrepancy reflects an in-vitro
      selection depending on the different entities. In 7 aneuploid clones of
      chondrosarcomas the chromosomal ploidy was calculated using the relative length
      of the chromosomes and compared with the DNA-ploidy of the native tumor. There
      was a close relation between both parameters of nuclear DNA-content. The
      interpretation of cytogenetic results is improved using a combination of
      karyotypic and DNA-cytometric examination. This is particularly important for the
      search for relations between numeric chromosomal aberrations and morphological
      parameters (grading).

PMID- 8992481
TI  - [An example for stepwise reduction of work site-induced formaldehyde exposure in
      pathology].
AB  - Occupational formaldehyde exposure in pathology depends on the efficiency of the
      ventilation system in use and may reach concentrations considerably above the
      current threshold limit values. The reduction of formaldehyde exposure by
      stepwise improvement of the ventilation system at a pathologist's workplace is
      presented as an example in this paper. Assessment of formaldehyde concentration
      by personal air sampling at a workplace originally equipped with a hood
      ventilation system resulted in values of up to 4 ml/m3 in the pathologist's
      breathing zone. Lowering the ventilation inlet to the working level by connecting
      the hood to a suction unit via a flexible hose resulted in an effective reduction
      of formaldehyde exposure to values of about 0.5 ml/m3. This simple and low-cost
      technical improvement had some uncomfortable side effects, such as current noise
      and wind chill, which could only be overcome by installing ventilated work tables
      according to modern technical standards.

PMID- 8992482
TI  - [Carcinoma-in-carcinoma metastasis. In situ DNA quantification and
      immunohistochemical diagnosis].
AB  - In the rare event of cancer-to-cancer metastasis, one malignant neoplasm spreads
      to a second carcinoma. To date, 42 such cases have been published in the English-
      and German-language literature. We report two additional patients, each with
      metastatic bronchial cancer present in a renal carcinoma. In addition to
      immunohistochemical examinations, we performed in situ DNA image cytometry of
      histologic preparations as a novel analytical technique to differentiate
      metastatic tissue from the host tumor. In both cases DNA histograms of metastatic
      tumor resembled those of the primary malignancy but were clearly dissimilar to
      the host tumor. In 70% of previously reported cases renal carcinoma was the host
      tumor while in 50%, cancer of the lung was the most frequent donor tumor.

PMID- 8992483
TI  - [Polypoid ulcerating endocarditis aortalis caused by Streptococcus viridans with
      perforation of the right atrium. Pathology and clinical aspects of 2 autopsy
      cases].
AB  - We report two cases of patients (one 65 and one 43 years of age, respectively)
      who died of Streptococcus-viridans induced endocarditis of the aortic valve with
      perforation into the right atrium. Whereas perforation in Staphylococcus-induced
      endocarditis is a common complication, it occurs rarely in Streptococcus-induced
      endocarditis. Because of its uncharacteristic symptoms, the endocarditis was
      clinically unknown in both cases and was recognized to be the cause of death only
      at autopsy. To reduce the large number of complications in patients suffering
      from endocarditis, it is necessary to confirm the diagnosis as soon as possible
      if endocarditis might be suspected.

PMID- 8992484
TI  - [Ekkehard Grundmann on his 75th birthday].

PMID- 8992485
TI  - [Digital handwriting recognition in data collection for autopsy reports with an
      Apple Newton].

PMID- 8992487
TI  - Monthly prostaglandin bibliography prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 8992486
TI  - Papers from a National Academy of Sciences Colloquium on Memory: Recording
      Experience in Cells and Circuits. Irvine, California, February 17-20, 1996.

PMID- 8992488
TI  - The endothelium of resistance arteries: physiology and role in hypertension.
AB  - The endothelium plays a very important role in the regulation of vascular
      function by way of its barrier role, by interaction with circulating cells such
      as platelets, which may release vasoactive or growth regulating agents, and
      through production of substances which modulate vascular tone and smooth muscle
      cell growth, and which may also exert antithrombotic effects. The endothelium of
      resistance arteries, vessels critically involved in generating resistance to flow
      and which play an important role in hypertension, has been studied mainly from
      the point of view of generation of agents which regulate vascular tone and
      growth. Endothelium-derived relaxing factors such as nitric oxide, prostacyclin,
      hyperpolarizing factors (EDHF) and possibly C-type natriuretic peptide (CNP), are
      counteracted by endothelium-derived contracting factors, which include
      endothelins and contracting factors (EDCF) which are less well characterized and
      appear to be cyclooxygenase products. In experimental hypertension in animals,
      and in human essential hypertension, these mechanisms may be altered. There may
      be a reduced generation of endothelium-derived nitric oxide and enhanced
      production of EDCF. Some of the mechanisms involved in the role these agents play
      in the physiology of resistance arteries and pathologically in hypertension will
      be reviewed.

PMID- 8992489
TI  - Endothelial permeability under physiological and pathological conditions.
AB  - Due to their special position at the tissue-blood interface, the endothelial
      cells are endowed with two mechanisms for handling plasma molecules: one,
      receptor-mediated endocytosis, which supplies nutrients for the cell's own
      metabolic needs; the other, direct transendothelial transport of material from
      plasma to the intima of arteries. Under normal physiological conditions, the
      latter transendothelial pathway is far more important than the endocytic one.
      Routes for exchange of both small and large plasma molecules include the clefts
      between adjacent endothelial cells (paracellular) and plasmalemmal vesicles.
      Paracellular transport is restricted to molecules smaller than 4 nm in diameter,
      and is the pathway for water filtration. Larger molecules, as large as 30 nm in
      diameter, are transported through plasmalemmal vesicles. Changes in endothelial
      permeability occur during inflammation, hypertension or diabetes.

PMID- 8992490
TI  - Cyclooxygenase and lipoxygenase inhibitors in cancer therapy.

PMID- 8992491
TI  - Endothelial and smooth muscle pharmacology of pre- and post-capillary
      microcirculation: correlation with plasma extravasation.

PMID- 8992492
TI  - The mechanical properties of the arterial wall in hypertension.
AB  - In hypertensive patients, the buffering function of large arteries is constantly
      altered, due to modifications in the viscoelastic properties of the arterial
      wall. Several in vivo models of the arterial circulation have been described to
      determine arterial compliance in animals and humans. The pressure dependency of
      arterial compliance is the main difficulty in evaluating the mechanical
      properties of large arteries in hypertension and establishing whether reduced
      arterial compliance is the simple mechanical consequence of the blood pressure
      elevation or reflects intrinsic alterations of the arterial wall. In comparison
      with the normotensive population, the carotid arterial wall is stiffer in
      hypertensive rats and humans, due to abnormalities in both the structural and the
      functional components. Interestingly, the presence of an intact and normal
      endothelium greatly influence vasomotor tone. The pathways by which the intrinsic
      modifications of the arterial wall may be reversed following drug treatment
      remain difficult to delineate. However, such considerations are clearly of
      importance for antihypertensive therapy, the goal of which may be not only the
      reduction of blood pressure but also improvement of the status of the
      hypertensive abnormalities of the arterial system.

PMID- 8992494
TI  - Pathophysiology of the vascular wall: the role of nitric oxide in renal disease.
AB  - Nitric oxide (NO) is formed in the endothelium by the constitutive enzyme NO
      synthase from the substrate amino acid L-arginine. As an endogenous vasodilator
      it contributes to renal arteriolar tone and modulates relaxation of the
      mesangium, thus contributing to regulation of glomerular microcirculation. NO
      also plays a role in regulating renal sodium excretion and renin release. It has
      antiplatelet and antithrombogenic effects and thus helps prevent thrombosis
      within the glomerular capillaries. In sepsis and sepsis-related syndromes, NO has
      a renoprotective role in that it aids in maintaining renal vasodilation and
      inhibiting platelet adhesion and aggregation. More knowledge of these effects may
      lead to the design of therapeutic interventions for preventing glomerular injury.

PMID- 8992493
TI  - Endothelial dysfunction in diabetes mellitus.
AB  - In the present study, we examined the pattern of Evan's blue (EB) extravasation
      over time and we verified the effect of two inhibitors of aldose reductase
      (sorbinil and ARI 509) as well as aminoguanidine, which modulate nitric oxide
      (NO) production, on streptozotocin-induced capillary extravasation abnormalities
      in the upper bronchi, heart, kidney, duodenum, pancreas, skeletal muscle and
      skin. Albumin extravasation was measured using the EB technique (20 mg/kg). On
      the third day, a transient decrease in EB leakage was observed in the lung (
      49%), heart (-29%) and skeletal muscle (-64%). These early changes in EB were
      transient, and values returned to normal there after. Later on, EB extravasation
      was significantly enhanced in the skin (+358, +680, +580, +525 and +365,
      respectively, at 2, 4, 5, 6 and 7 weeks of diabetes), the duodenum (+101, +160,
      +92, +124 and +76%), the upper bronchus (+70, +113, +70, +41 and +25%) and the
      pancreas (+43, +102, +46, +15 and +78%). In the kidney, the increase of EB
      extravasation was significant at 2 weeks (26%), and from 5 to 7 weeks (+12, +22,
      +36%). The chronic treatment of diabetic rats with aminoguanidine normalized
      capillary permeability in most tissues, suggesting that NO is involved in the
      development of endothelium dysfunction in this streptozotocin-induced diabetic
      model. Treatment with aldose reductase inhibitors selectively normalized EB
      extravasation in the kidney.

PMID- 8992496
TI  - Antihypertensive drugs and endothelial cell function.
AB  - Arterial hypertension is associated with increased capillary permeability, a
      possible contributor to the vascular remodeling process which could be involved
      in certain pathological conditions arising from elevated blood pressure. This
      study evaluated the effects of various antihypertensive drugs on capillary
      permeability in the normal rat, using Evan's blue dye (EB) as a marker of albumin
      extravasation. The results reveal that acute injection of certain diuretics
      (furosemide, indapamide, hydrochlorothiazide) increase while others (amiloride,
      cicletanine) decrease capillary permeability via stimulation of the
      cyclooxygenase pathway. 10 day gavage with indapamide, amiloride and cicletanine,
      as well as angiotensin-converting enzyme (ACE) inhibitor perindopril and calcium
      channel blockers nifedipine and verapamil decreases capillary permeability,
      whereas furosemide, hydrochlorothiazide, ACE inhibitor captopril and calcium
      channel blocker clentiazem do not modify or increase EB extravasation. Hence,
      selected antihypertensive agents reduce capillary permeability and could
      therefore have a supplemental protective vascular effect, in addition to their
      lowering arterial pressure.

PMID- 8992495
TI  - Eicosanoid modulation of the norepinephrine effect on blood pressure and renal
      hemodynamics in humans.
AB  - The main objective of this study was to investigate the role of eicosanoids in
      modulating the effect of norepinephrine (NE) on blood pressure and renal
      hemodynamics during NE administration. Eight healthy volunteers were randomly
      assigned to three (1 week apart) infusion periods (180 min) with either dextrose
      5% or NE, with or without indomethacin pretreatment. Pressor doses of NE induced
      marked alterations in renal hemodynamics and concomitant increases in eicosanoid
      excretion rates. The production of the vasodilatory prostacyclin (PGI2), as
      reflected in the excretion rate of the stable metabolites 6-keto-prostaglandin
      (PG)F1(alpha) and 2,3-dinor-6-keto-PGF1(alpha), was 2.7 times higher than that of
      the constrictor thromboxane (TX)A2, which was measured as the stable derivative
      TXB2. Indomethacin pretreatment blunted the NE-induced augmentation in eicosanoid
      excretion and resulted in further increases in arterial pressure and in renal
      vascular resistance. These results demonstrate that PGI2 attenuates the systemic
      and the renal hemodynamic vasoconstrictor effect of NE in normotensive control
      normal subjects.

PMID- 8992497
TI  - Antihypertensive therapy and wave reflections.
AB  - Studies of pulsatile arterial hemodynamics have emphasized that the pulsatile
      component of pulse pressure has two important characteristics: (i) it increases
      from central to peripheral arteries for a similar value of mean arterial
      pressure, and (ii) it is dominantly influenced by the amplitude and timing of the
      backward pressure wave. Although these important aspects of wave reflections have
      been poorly investigated in the field of hypertension, they may be easily studied
      noninvasively in humans on the basis of the analysis of the pulse wave contour of
      carotid and aortic blood pressure. Increased wave reflections returning toward
      the thoracic aorta during systole may have deleterious consequences on the
      structure and function of the heart. Some (but not all) antihypertensive drugs
      may contribute to decrease and/or to delay wave reflections in association with
      blood pressure reduction.

PMID- 8992498
TI  - Seasonal variation in levels of prostaglandins D2, E2 and F2(alpha) in the brain
      of a mammalian hibernator, the Asian chipmunk.
AB  - Seasonal changes in the in vivo levels of the prostaglandins (PGs) PGD2, PGE2,
      and PGF2(alpha) were measured in the brain of the male Asian chipmunk, Tamias
      asiaticus (n = 111), which underwent hibernation during the period between
      November and March. The mean level of PGD2 ranged from 36.0 to 85.2 pg/g tissue
      from June to October and remained essentially unchanged (80.5 pg/g tissue) in
      December. However, the mean PGD2 level rose significantly to 128.6 pg/g tissue in
      February, and returned to 75.2 pg/g tissue in the following April, suggesting a
      correlation between PGD2 and hibernation phenomenon. While PGE2 level did not
      vary significantly throughout the year, PGF2(alpha), which appeared to be the
      most abundant among the three prostanoids, showed a marked circannual rhythm with
      a trough of 51.6 pg/g tissue in July, rising to 391.6 pg/g tissue in February and
      reaching the peak value of 492.7 pg/g tissue in April, the reproduction period.

PMID- 8992499
TI  - Formation of nitrosyl hemoglobin and nitrotyrosine during murine leishmaniasis.
AB  - Peroxynitrite, the potent oxidant formed by the fast reaction between nitric
      oxide and superoxide anion, has been suggested to be the reactive intermediate
      responsible for some of the pathologies associated with an over-production of
      nitric oxide. In this report, we demonstrate that both nitric oxide and
      peroxynitrite are formed during infection of the susceptible mouse strain,
      BALB/c, with Leishmania amazonensis. Nitric oxide was detected as the nitrosyl
      hemoglobin complex by EPR analysis of blood drawn from mice at 35, 64 and 148
      days of infection. The levels of nitrosyl hemoglobin complex increased with
      disease evolution, which in the murine model used is characterized by skin
      lesions, ulceration and visceralization of the parasites. Peroxynitrite formation
      was inferred from immunoreaction of homogenates obtained from footpad lesions in
      the late stages of the infection with anti-nitrotyrosine antibody; homogenates
      from parasites drawn from the lesions were also immunoreactive, although to a
      lesser extent. Analysis of protein homogenates by gel electrophoresis and western
      blots suggests that peroxynitrite may degrade proteins in vivo, in addition to
      nitrating them. The results demonstrate that peroxynitrite is formed during
      murine leishmaniasis and may play a role in the aggravation of the disease.

PMID- 8992500
TI  - Development of monoclonal antibodies against a riboflavin-tryptophan photoinduced
      adduct: reactivity to eye lens proteins.
AB  - We describe here the development of monoclonal antibodies to the hapten
      tryptophan-riboflavin, generated by irradiation of a solution of bovine serum
      albumin in the presence of riboflavin. The specificity of the three obtained
      monoclonal antibodies, named 1E6, 5H5, 5A8 all belonging to the IgG1 isotype, was
      assessed by a competitive enzyme-linked immunosorbent assay in the presence of an
      increasing concentration of the tryptophan-riboflavin adduct, obtained from an
      irradiated riboflavin-sensitized tryptophan solution. It was demonstrated that
      the tryptophan-riboflavin antibodies react with the soluble proteins of the eye
      lens; this reaction was more intense in the old rat lenses as compared to the
      young ones, and a maximum binding of the antibodies was obtained with the soluble
      protein fraction from the human cataractous lens. By indirect immunofluorescence,
      a reactivity associated with the protein matrix, localized in the lens central
      zone, was observed. In the peripheral zone of the lens, where the younger cells
      are found, a marked immunofluorescent emission was observed on structures
      preferentially localized in the nuclei.

PMID- 8992501
TI  - Synthesis, photoreactivity and cytotoxic activity of caged compounds of L-leucyl
      L-leucine methyl ester, an apoptosis inducer.
AB  - L-Leucyl-L-leucine methyl ester (Leu-Leu-OMe), an apoptosis inducer in natural
      killer cells and macrophages, was caged with trans-o-hydroxycinnamoyl (3a-d),
      trans-o-mercaptocinnamoyl (4) and o-nitrobenzyl derivatives (5a, b), and the
      photochemical reactivity of these derivatives in phosphate-buffered saline
      containing 1% dimethyl sulfoxide and their immunological properties were studied.
      All of the derivatives exhibited absorption at wavelengths longer than the UVB
      region. Although 3a-d and 4 were expected to isomerize to a cis isomer, which
      then cyclizes intramolecularly to give Leu-Leu-OMe and a coumarin derivative,
      cyclization efficiency was not satisfactory except for 3a. However, 3a itself
      caused necrosis (cell swelling) of U937 cells (a myeloid cell line). In contrast,
      5a and b released Leu-Le-OMe quickly and efficiently and did not affect U937
      cells. Although irradiated 5b induced necrosis, irradiated 3a and 5a induced
      apoptosis in these cells, as evidenced by a decrease in cell size.

PMID- 8992502
TI  - Measurement of UVA exposure to solar radiation.
AB  - Exposure to solar UVA (320-400 nm) radiation can damage DNA and lead to skin
      disorders. Conventional dosimetry using a single piece of polysulfone or diglycol
      carbonate (CR-39) cannot provide accurate measurement of the biologically
      effective irradiance for erythema for the UVA waveband. A package employing four
      dosimeters (polysulfone, nalidixic acid, 8-methoxypsoralen and phenothiazine) has
      been shown to be effective for use as a spectrum evaluator for evaluating the UVA
      source spectrum. In Brisbane, on a horizontal position, the spectrum evaluator
      requires about 5 min exposure in summer and about 20 min in winter. This amounts
      to about 10 mJ cm-2 of erythemal UV radiation.

PMID- 8992503
TI  - Structural and functional changes in catalase induced by near-UV radiation.
AB  - Part one of this study shows that exposure of purified beef liver catalase in
      buffered solutions to BL lamps that provide a mixture of 99% UVA and 1% UVB (to
      be labeled UVA) alters its chemistry and enzymatic activity. Thus, its spectral
      absorbance lost detail, it aggregated and exhibited a lower isoelectric point and
      its enzymatic activity was substantially reduced. These photochemically induced
      changes were increased by irradiation in phosphate buffer or in physiological
      medium (minimal essential medium) containing riboflavin and tryptophan. Neither
      alpha-tocopherol nor deferoxamine were protective against these UVA-induced
      changes in pure catalase. We further investigated the effect of UVA radiation on
      the activity of catalase in cultured lens epithelial cells and the protective
      effects of antioxidants. Cultured lens epithelial cells of rabbits and squirrels
      were exposed to near-UV radiation with representation in the UVA region of 99%
      and 1% UVB. Catalase assays were done on homogenate supernatants of cells kept
      dark or UV exposed. In some instances, cells were cultured in medium containing
      alpha-tocopherol or deferoxamine prior to UV radiation. Comparisons were made
      between UV-exposed lens cell catalase activity when exposure was done with or
      without the antioxidants. The UVA radiation was strongly inhibitory to both
      rabbit and squirrel lens epithelial cell catalase activities. The range of fluxes
      of near UV radiation was compatible with that which could reach the lens from the
      sunlit environment. Catalase inactivation was lessened in cells preincubated with
      alpha-tocopherol and deferoxamine. This suggests that both singlet oxygen and
      hydroxyl radical formation may be involved in near-UV damage to lens epithelial
      cell catalase. Such inhibition of catalase by near-UV would enhance H2O2 toxicity
      and stimulate SH oxidation so as to damage the lens.

PMID- 8992504
TI  - Preprogrammed and programmed cell death mechanisms of apoptosis: UV-induced
      immediate and delayed apoptosis.
AB  - Equitoxic doses (10% clonogenic survival) of UV radiation (UVR) from the three
      waveband regions, i.e. UVA1 (340-400 nm), UVB (290-320 nm) and UVC (200-290 nm),
      were shown to induce immediate or delayed apoptosis in L5178Y-R murine lymphoma
      cells. Membrane and DNA damage were shown to be the most probable initiators of
      UVA1-induced immediate or UVR-induced delayed apoptosis, respectively. These UV
      induced apoptotic processes appeared to utilize two different "core" biochemical
      mechanisms; however, one core mechanism could be initiated at two distinct sites
      (e.g. membrane or DNA) and result in disparate kinetics. In an attempt to resolve
      this mechanistic issue, the dependence on macromolecular synthesis of each UV
      induced apoptotic mechanism was investigated. In the absence of UVR, inhibition
      of either transcription (actinomycin D) or translation (cycloheximide) induced
      apoptosis in a concentration- and time-dependent manner. These results suggest
      that an apoptotic mechanism exists that does not require macromolecular synthesis
      postinsult (constitutive). The UVR data demonstrate that UVA1-induced immediate
      apoptosis utilizes this constitutive mechanism (preprogrammed), while UVR-induced
      delayed apoptosis utilizes the well-known inducible mechanism (programmed).
      Therefore, there are two different core biochemical mechanisms of apoptotic death
      available to each cell: preprogrammed (constitutive) and programmed (inducible)
      cell death.

PMID- 8992505
TI  - The selective uptake of benzoporphyrin derivative mono-acid ring A results in
      differential cell kill of multiple myeloma cells in vitro.
AB  - High-dose chemotherapy (HDCT) and autologous bone marrow/blood stem cell
      transplantation are an effective combination for treating a number of malignant
      disorders. The contamination of the autograft by malignant cells may be a reason
      for recurrences in spite of this treatment, for instance, in multiple myeloma.
      Therefore, we evaluated the use of photodynamic therapy (PDT) using the
      photosensitizer benzoporphyrin derivative mono-acid ring A (BPD-MA) on multiple
      myeloma cells in comparison to the components of the normal bone marrow (NBM) and
      peripheral blood apheresis product. Flow cytometry was used to measure
      differential BPDMA uptake of NBM components: namely lymphocytes, monocytes,
      granulocytes and enriched hematopoietic stem cell (CD34+) populations and also
      the multiple myeloma cell lines OCI-MY7 and OCI-MY4. When each population was
      measured individually, the order of uptake was [OCI-MY7/MY4] > [CD34+] >
      [granulocytes] = [monocytes] >> [lymphocytes]. Further, clonogenic assay was used
      to demonstrate surviving fractions for OCI-MY7, OCI-MY4 and NBM in vitro. The
      LD90 for OCI-MY7 and OCI-MY4 was between 10 and 20 ng/mL BPD-MA whereas this
      concentration did not show any significant cell kill for the colony-forming units
      granulocyte/macrophage (CFU-GM) and burst-forming units-erythrocyte (BFU-E). When
      the NBM was "contaminated" with multiple myeloma cells in vitro, the LD90 for OCI
      MY7 in this cell mixture was shifted to between 40 and 80 ng/mL BPD-MA. However,
      at 40 ng/mL BPD-MA at least 50% of normal CFU-GM and BFU-E colonies survived. For
      CFU-GM and BFU-E derived from the enriched CD34+ cell population, BPDMA up to a
      concentration of 80 ng/mL did not significantly reduce the surviving fractions.
      We have observed a 3-4 log therapeutic window with differential cell kill when
      comparing multiple myeloma cell lines to the components of the NBM and apheresis
      product in vitro. We conclude, that BPD-MA is a molecule potentially useful as an
      ex vivo purging agent.

PMID- 8992506
TI  - UVB induces IL-12 transcription in human keratinocytes in vivo and in vitro.
AB  - Human epidermal cells produce a wide range of cytokines, including those
      characteristic of Th2-like responses such as interleukin (IL)-4 and IL-10. As
      well, keratinocytes have recently been shown to produce Th1-like cytokines such
      as IL-12. Exposure to UVB has profound effects on the skin and systemic immune
      system, which is in part mediated by secretion of tumor necrosis factor (TNF)
      alpha by epidermal cells. Because IL-12 induces production of TNF-alpha by
      certain cells of the immune system, we sought to determine whether UVB is an
      inducer of IL-12 gene expression in epidermal cells. Human epidermal cells were
      exposed to UVB radiation in vivo, isolated by suction blister technique and
      trypsinization and transcription of the IL-12 p35 and p40 chains was examined by
      RT-PCR. We found the p35 chain of IL-12 to be constitutively expressed and the
      p40 chain inducible by UVB irradiation. Because epidermis consists of a
      heterogenous cell population with distinct cytokine repertoires, we sought to
      determine the cellular source of the IL-12 message after UVB exposure. After
      depleting UVB-exposed epidermal cells for DR+ cells, no reduction in the IL-12
      activity was detected, suggesting that keratinocytes are a source of IL-12
      transcripts in UVB-exposed human epidermis. This was supported by the up
      regulation of IL-12 p40 transcripts in UV-irradiated cultured keratinocytes that
      were devoid of DR+ cells. Up-regulation of IL-12 p40 gene expression by UVB as
      demonstrated here, taken together with the finding that keratinocytes also up
      regulate IL-10 transcription, suggests that there is a complex interplay between
      Th1- and Th2-like epidermis-derived cytokines following exposure to UVB.

PMID- 8992507
TI  - Photodynamic imaging of a rat pancreatic cancer with pheophorbide a.
AB  - Laser-induced fluorescence of pheophorbide a (Ph-a) was used for in vitro
      photodynamic imaging (PDI) of a rat pancreatic acinar tumor. A 400 nm excitation
      induced a 470 nm autofluorescence and a 678 nm dye fluorescence in tumors and
      their surrounding pancreas 24 h after a 9 mg kg-1 body weight Ph-a intravenous
      administration. With lower intensities in these blood-rich tumors than in
      pancreas, Ph-a fluorescence signals are unable to provide tumor images. A
      dimensionless function (the ratio of Ph-a fluorescence by autofluorescence,
      called Rt for the tumor and Rp for the pancreas) was used for fluorescence
      contrast calculation (C = Rt/Rp) between six tumors and their paired pancreas.
      Among five available laser excitation wave-lengths, only the 355 nm excitation
      gave a distinctive contrast (C = 1.5). The PDI of six intrapancreatic tumors and
      their intraperitoneal metastasis and of two control normal pancreas was thus
      performed ex vivo using a 355 nm excitation source delivered by a tripled Nd:YAG
      laser and a charged-coupled device camera. Fluorescence images were recorded at
      680 nm (dye), 640 nm (background) and 470 nm (autofluorescence) through three
      corresponding 10 nm width bandpass filters. Computed division for each pixel of
      Ph-a fluorescence values by autofluorescence generated false color image. In this
      way, contrasted tumor images were obtained. But in five out of six animals false
      positive images were present due to an autofluorescence decrease in some normal
      pancreatic areas. A 470 nm autofluorescence imaging on the same tumors gave in
      all cases false-positive image and false-negative in half of the cases. These
      observations suggest that autofluorescence alone is unable to achieve accurate
      PDI of pancreatic carcinoma and that using Ph-a as a PDI dye needs strong
      improvements.

PMID- 8992508
TI  - Ultraviolet spectral energy differences affect the ability of sunscreen lotions
      to prevent ultraviolet-radiation-induced immunosuppression.
AB  - Acute exposure to UV radiation causes immunosuppression of contact
      hypersensitivity (CH) responses. Past studies conducted with unfiltered sunlamps
      emitting nonsolar spectrum UV power (wavelengths below 295 nm) or using excessive
      UV doses have suggested sunscreens may not prevent UV-induced immunosuppression
      in mice. This study was thus designed to evaluate critically the effects of
      different UV energy spectra on the immune protection capacity of sunscreen
      lotions. Minimum immune suppression doses (MISD), i.e. the lowest UV dose to
      cause approximately 50% suppression of the CH response to dinitrofluorobenzene in
      C3H mice, were established for three artificial UV sources. The MISD for each UV
      source was 0.25 kJ/m2 for unfiltered FS20 sunlamps (FS), 0.90 kJ/m2 for Kodacel
      filtered FS20 sunlamps (KFS), which do not emit UV power at wavelengths < 290 nm,
      and 1.35 kJ/m2 for a 1000 W filtered xenon arc lamp solar simulator. Using MISD
      as baseline, sunscreens with labeled sun protection factors (SPF) of 4, 8, 15 and
      30 were tested with each UV source to establish their relative immune protection
      factors. The immune protection factor of each sunscreen exceeded its labeled SPF
      in tests conducted with the solar simulator, which has a UV power spectrum (295
      400 nm) similar to that of sunlight. Conversely, sunscreen immune protection
      factors were significantly less than the labeled SPF in tests conducted with FS
      and KFS. Comparison of the immunosuppression effectiveness spectra showed that
      relatively small amounts of nonsolar spectrum UV energy, i.e. UVC (200-290 nm)
      and/or shorter wavelength UVB (between 290 and 295 nm), produced by FS and KFS
      contributes significantly to the induction of immunosuppression. For example,
      36.3% and 3.5% of the total immunosuppressive UV energy from FS and KFS,
      respectively, lies below 295 nm. Sunscreen absorption spectra showed that
      transmission of immunosuppressive UV energy below 295 nm for FS was at least
      eight-fold higher than that for KFS. Compared to the solar simulator UV spectrum
      the transmission of nonsolar immunosuppressive UV energy through sunscreens was >
      15-fold higher for FS and > or = 1.5-fold higher for KFS. These data demonstrate
      that relevant evaluations of sunscreen immune protection can only be obtained
      when tests are conducted with UV sources that produce UV power spectra similar to
      that of sunlight and UV doses are employed that are based on established MISD.

PMID- 8992509
TI  - Distribution and excretion of radiolabeled temoporfin in a murine tumor model.
AB  - The biodistribution and excretion of temoporfin (tetra[m-hydroxyphenyl]chlorin, m
      THPC), a recently developed photosensitizer, was investigated in BALB/c mice.
      [14C]temoporfin was administered intravenously (0.73 mumol/kg) to tumor-free mice
      or to mice implanted with the Colo 26 colorectal carcinoma. Blood, tissue and
      fecal samples were collected for 35 days and 10 days postdose from tumor-free
      mice and tumor-bearing mice, respectively. Blood concentrations fell rapidly such
      that at later time points they were indistinguishable from background counts.
      Tumor concentrations rose to a peak of 0.34 microgram temoporfin equivalents/mL
      at 2 days and then declined in parallel (log plot) with the blood concentrations.
      Tumor: tissue ratios at 2 days for skin, adipose tissue and skeletal muscle
      underlying the tumor were 1.5, 2.3 and 3.8, respectively. By 4 days the
      corresponding values were 1.6, 3.4 and 4.0. Nearly 40% of the administered
      radioactivity was excreted in the feces in the first 24 h and more than 80% had
      been excreted by 20 days. Less than 0.2% of the dose was recovered from the
      urine. An elimination half-life of 10-12 days was calculated from the excretion
      data.

PMID- 8992511
TI  - On the roles of urocanic acid in photoimmunosuppression: attempted photorepair of
      urocanic acid-DNA cyclobutane adducts with DNA photolyase.
AB  - It has been reported that UV-induced immunosuppression can be reversed by
      photoreactivation or exposure to T4 endonuclease V, two treatments that can
      repair cyclobutane pyrimidine dimers. These observations, together with the known
      role of urocanic acid (UA) in UV-induced immune suppression, prompted us to study
      the ability of DNA photolyase to repair UA-DNA cyclobutane photoadducts in single
      stranded calf thymus DNA. We did not detect any release of UA, with a sensitivity
      implying that photolyase is at least 2900 times less active toward UA-DNA adducts
      than toward cis-syn thymine-thymine dimers. This indicates that any reversal of
      photoimmunosuppression by photoreactivation cannot significantly involve cleavage
      of UA-DNA cyclobutane adducts.

PMID- 8992510
TI  - Lutetium texaphyrin (PCI-0123): a near-infrared, water-soluble photosensitizer.
AB  - Lutetium texaphyrin, PCI-0123, is a pure, water-soluble photosensitizer with a
      large broad absorption band centered at 732 nm. The compound was tested for
      photodynamic therapy (PDT) effectiveness in a murine mammary cancer model. The
      texaphyrin macrocycle as illustrated by magnetic resonance imaging and 14C
      radiolabeled texaphyrin studies was shown to be tumor selective; a tumor-to
      muscle ratio of 10.55 was seen after 5 h. Lutetium texaphyrin, at a drug dose of
      20 mumol/kg with irradiation 5 h postinjection at 150 J/cm2 and 150 mW/cm2, had
      significant efficacy (P < 0.0001) in treating neoplasms of moderate size (40 +/-
      14 mm3) and also had significant efficacy (P < 0.0001) in treating larger
      neoplasms (147 +/- 68 mm3). The PDT efficacy was correlated with the time
      interval between PCI-0123 administration and light exposure. A 100% cure rate was
      achieved when photoirradiation took place 3 h postinjection compared to 50% for 5
      h using 10 mumol/kg and 150 J/cm2 at 150 mW/cm2. The PDT efficacy was
      attributable to the selective uptake/retention of the texaphyrin photosensitizer
      in addition to the depth of light penetration achievable at the 732 nm laser
      irradiation.

PMID- 8992512
TI  - [Gentle psychiatry--metamorphosis of violence?].
AB  - The basic assumptions of reform psychiatry aim at the establishment of a benign,
      i.e. peaceful therapeutic regime which promotes the experience of meaningful
      interpersonal relationships. Yet purpose and therapeutic reality often show
      discrepancies. The peaceful dialogue is jeopardized by the psychiatric disorder
      itself, furthermore by the chimera of peacefulness which prevents "gentle
      psychiatry" from recognizing its own strategies of stigmatization and expulsion.
      Ideologies which take for granted free decision making even for those who are
      restricted by their illness tend to give legitimation for the withdrawal of
      necessary help. Especially dangerous patients are at risk of being expelled by a
      "gentle psychiatry" which intends to preserve the professional identity of
      goodness for the therapist.

PMID- 8992513
TI  - [Mental competence of dementia patients to execute a will].
AB  - Instruments allowing to give a psychiatric expertise on the ability of demented
      people to give a will are needed. Criteria for an estimation of the course of
      dementing illnesses and for an increased suggestibility in coming to a decision
      are critically reviewed.

PMID- 8992514
TI  - [Family group in schizophrenic diseases. Overview, personal concept and report of
      experiences].
AB  - Improved treatment measures of schizophrenic inpatients often lead to early
      discharge and thus, may be stressful for the relatives. Different styles of
      coping with this new situation may sometimes be followed by depression and
      resignation in the relatives. This may have negative effects on the course of the
      illness. Family group-therapy may be a way to help them. We will give an overview
      of the different forms of family/relative-groups and finally present our own
      concept.

PMID- 8992515
TI  - [Quality assurance in clinical social work: how do social workers judge the
      success of their interventions?].
AB  - Therapy outcome is an important criterium for quality assurance. In this study,
      clinical social workers themselves estimated the outcome of their interventions
      in 2643 admissions of 2038 patients to a psychiatric hospital. These inpatients
      had been referred by a psychiatrist to the social worker and comprised 27 % of
      all patients admitted to the hospital within 11 years. The study purpose was to
      investigate how the outcome estimates relate to clinical and sociodemographic
      variables of the patients, to their specific problems, and to the applied
      interventions. The fewer areas of problems were perceived and the more
      interventions were performed, the more positive these interventions were
      evaluated. Administrative interventions were seen as more successful than
      counseling. Outcome estimates were particularly positive in long and intensive
      therapies.

PMID- 8992516
TI  - [Management of psychiatric patients in the community--developments up to now,
      current problems and future perspectives exemplified by the Tubingen district].
AB  - The development of the care of mentally ill persons in the last 25 years is shown
      by the example of the district of Tubingen with about 200,000 inhabitants, a
      district that did not take part in the model program of the Government.
      Considering the current care situation, the problems of cooperation and
      coordination as well as the ensuring of quality, which are actually most
      important, are discussed; approaches for solutions are outlined. We try a view on
      the coming 25 years.

PMID- 8992517
TI  - [Non-compliance and lack of indications for depot treatment as reasons for
      exclusion from adequate prevention of recurrence].
AB  - OBJECTIVE: The paper reports on the recruitment of a multicenter study on
      ambulant prophylactic treatment of schizophrenic disorders. METHODS: For a study
      of the relapse-preventative effect of different dose patterns of Flupentixol, a
      screening phase was carried out among of 1129 schizophrenic patients. The aim of
      the screening phase was to establish the criteria for exclusion or inclusion in
      the treatment phase of the study. RESULTS: Only 62 patients could be included.
      The reason for 54 patients not being included was a lack of compliance from
      either the patient or the clinician. The meaning of patient- and therapist
      compliance in carrying out a multicenter study is also discussed.

PMID- 8992518
TI  - [Controlled long-term prevention of unipolar depression with antidepressive
      agents of the second generation (SSRI)].
AB  - Relapse and recurrence are common following successful short-term treatment of
      unipolar depression. Evidence from a number of controlled double-blind
      investigations indicates that a patient with a history of depressive episodes is
      best protected against future episodes by being maintained on the same
      antidepressant agent at the same dose that was used to treat the acute episode.
      Newer agents, such as paroxetine, sertraline, and fluoxetine, have been studied
      in controlled manner for up to one year. The effectiveness of the SSRI in
      preventing recurrence of depression has been well established in six
      investigations.

PMID- 8992519
TI  - [Bradycardia after beginning therapy with metoprolol and paroxetine].
AB  - Because of their low incidence of adverse effects SSRI are prescribed more and
      more frequently in patients with depressive disorders. SSRI inhibit different
      subsystems of cytochrome-P 450-oxydase. Especially during co-administration of
      SSRI with antipsychotic and antiarrhythmic drugs pharmacokinetic interactions
      have to be observed carefully. In this presentation a case of bradycardia after
      co-administration of paroxetine and metoprolol is reported. Drug history and a
      careful drug monitoring are necessary requirements to avoid serious adverse
      effects.

PMID- 8992521
TI  - [Complications after benzodiazepine dependence].

PMID- 8992522
TI  - [Suicidal behavior in schizophrenia--on the verbal behavior of 2 suicidal
      patients in group therapy].

PMID- 8992520
TI  - [Delusional "pseudotranssexualism" in schizophrenic psychosis].
AB  - The case of a 32-year old man suffering from a 10-year course of schizophrenia is
      presented. The man's delusions include the conviction of being of the opposite
      sex and thus, he applied for an operational correction of his gender according to
      the law of transsexualism. Based on the evident problems arising from this case,
      the differential diagnosis of genuine transsexualism is discussed.

PMID- 8992523
TI  - [Benzodiazepine withdrawal syndrome in low dose dependency].

PMID- 8992524
TI  - [Chronic dissociative hemiparesis in borderline personality disorder].

PMID- 8992526
TI  - [Autistic-undisciplined thinking in medicine and overcoming it by Eugen Bleuler].

PMID- 8992525
TI  - [Paranoid psychosis after treatment with the antibiotic ofloxacin].

PMID- 8992527
TI  - Rediscovering the science of the history of life.

PMID- 8992529
TI  - [40 years of using sulfonylurea derivatives for treatment of diabetes].
AB  - The structure and effects of sulfonylurea derivatives were described. Today the
      second generation of sulfonylureas rather is prescribed because of its lower
      dosage and better peripheral activity. The non-insulin-dependent diabetes after
      weight reduction and failure of other oral therapy is the main indication to
      introduction of sulfonylurea derivates.

PMID- 8992528
TI  - [Present status and future of study on cell cycle (discussion)].

PMID- 8992530
TI  - [Insulin resistance and hyperinsulinemia--clinical aspects].
AB  - A group of metabolic disorders including insulin resistance and hyperinsulinemia,
      impaired glucose tolerance, visceral obesity, hypertension, dyslipidemia,
      hyperuricemia, hypercoagulability and microalbuminuria determine the risk for the
      development of atherosclerosis, coronary artery disease and cerebral vascular
      disorders. Although available studies on the pathogenesis of the metabolic
      syndrome are equivocal, it is most frequently hypothesized that hereditary of
      insulin resistance leads to the remaining metabolic disorders including diabetes
      mellitus, atherosclerosis and coronary artery disease. Despite pathogenetic
      controversies, there are convincing arguments for the diagnosis of the metabolic
      syndrome and search for therapy improving insulin sensitivity and reducing
      hyperinsulinemia thus preventing the development of diabetes mellitus and
      coronary artery disease.

PMID- 8992531
TI  - [Lipid disorders in non-insulin dependent diabetes--principles of treatment].
AB  - Hyperlipoproteinemia is one of the main coronary risk factors. Lipid metabolism
      disorders occur in about 40-60% of patients with NIDDM. Hyperlipidemia in
      diabetics is related to diabetes control, presence of diabetic nephropathy, diet,
      some drugs and genetic factors. Lipid metabolism disorders in NIDDM comprise
      qualitative changes--usually increase of serum triglyceride concentration and
      decrease of HDL--cholesterol, and qualitative changes of lipoprotein composition,
      glycation and oxidation. The first steps of hypolipemic therapy are good control
      of diabetes, reduction of overweight, hypolipidemic diet, and if a goal level is
      not achieved--farmacotherapy. Hypolipidemic treatment should be relevant in
      reduction of cardiovascular diseases in diabetic patients.

PMID- 8992533
TI  - [The role of glipizide in the treatment of non-insulin dependent diabetes].
AB  - The structure and effect of glipizide, the second generation derivates of
      sulfonylurea were described. The special role in the treatment of polymetabolic
      syndrome of this drug was stressed.

PMID- 8992535
TI  - [The possibility of preventing non-insulin dependent diabetes].
AB  - High and rapid growing up incidence of non-insulin-dependent diabetes mellitus
      (NIDDM) leading to severe chronic complications and significant reduction of life
      expectancy, as well as a huge rise of direct and indirect costs connected with
      the disease oblige to search for methods of its prevention. Scientific basis of
      the prevention grounded on a knowledge of genetic and environmental pathogenetic
      factors as well as natural history of NIDDM does exist. The article discussed
      shortly the strategy of prevention based on attempts of life style (diet,
      physical exercise) and pharmacological interventions. Actually, primary
      prevention of NIDDM seems to be hypothesis requiring further testing, but the
      possibility and necessity of secondary and tertiary prevention is
      incontroversible.

PMID- 8992534
TI  - [Glipizide--a short-acting sulphonylurea derivative].
AB  - Glipizide is a second generation of sulphonylurea compound, effective in lowering
      of blood glucose, well-tolerated as well as safe during long-term treatment.
      Glipizide is the agent characterized by rapid pharmacological action. It is
      indicated both in monotherapy and combined treatment with insulin or biguanides.
      This drug is particularly indicated in diabetes treatment in elderly patients due
      to short time of action as well as lack of hyperinsulinemic effect. Data in
      literature suggest that glipizide combined with insulin is much more effective in
      the induction of remission in recent diagnosed diabetes when compared to
      intensive insulin therapy.

PMID- 8992532
TI  - [Lipid disorders in patients with diabetes].

PMID- 8992536
TI  - [Organization of diabetic care through family physician care].
AB  - The author makes review the actual status of care for diabetic patients in the
      region of Szczecin. He also proposes, on the data base from medical literature,
      the model to be realized by the family practice physician.

PMID- 8992537
TI  - [Insulin resistance and non-insulin dependent diabetes in the course of Werner's
      syndrome. Case report].
AB  - A case of Werner's syndrome has been reported. The patient presented with insulin
      resistance, non insulin dependent diabetes mellitus and muscular atrophy.

PMID- 8992538
TI  - [Serum lipids in persons over 90 years of age].
AB  - Because of different views on the significance of the serum lipids as a risk
      factor of atherosclerosis in the elderly we evaluated the levels of total
      cholesterol (CH), HDL-cholesterol (HDL-CH) and triglyceride (TG) in the group of
      56 very old (over the 90), who were in a good health condition. Desirable values
      of lipids were found respectively: CH in 55.4% of subjects, HDL-CH in 85.7% and
      TG in 89.3%. In the elderly with hypercholesterolemia (CH > 250 mg/dl) we
      simultaneously found high level of HDL-CH (x = 69.3 mg/dl). CONCLUSIONS: The
      serum lipids levels in the elderly over 90 were generally within the limit of
      desirable values. On the other hand subjects who had higher level of cholesterol
      had also high level of HDL-CH (69.3 mg/dl). Considering our results we came to
      the conclusion that high level of HDL-CH is one of the favoring factors to reach
      an advanced age.

PMID- 8992539
TI  - [Selected clinical characteristics of insulin dependent diabetes (IDDM)
      discovered in the years 1990-1992 in patients 0-29 years of age from the Rzeszow
      voivodship].
AB  - The aim of the study was to analyse the clinical symptoms preceding the final
      diagnosis of IDDM, some features of the illness at the moment of the diagnosis
      and variants of treatment. We examined 54 patients, among them 28 males and 26
      females. There were 23 and 31 persons between 0-14 and 15-29 years of age,
      respectively. The data were accumulated using questionnaires. We have shown that
      the newly diagnosed IDDM cases were characterised by typical clinical symptoms,
      early detection and 100% hospitalization. Most of the patients or their parents
      underwent the diabetic education during the patients first stay at hospital. Only
      monocomponent or human insulins were used in the case of patients between 0-14
      years of age. Among the group 15-29 years of age in 13% of patients ordinary
      insulins (regular, NPH, Lente group) were administered as well. Intensive insulin
      therapy was used exclusively, but sporadically in the patients 15-29 years of
      age.

PMID- 8992540
TI  - [QT dispersion].
AB  - The study presents the modern concepts on QT dispersion which is regarded as one
      of the reasons of potentially dangerous cardiac arrhythmias. The measurement of
      QT interval is based on standard 12-lead electrocardiogram or 24-hours Holter
      monitoring record. The study describes the rules of QT dispersion measurement and
      the most common problems connected with it. The changes of QT dispersion in
      ischaemic heart disease, heart failure, cardiac arrhythmia and prolonged QT
      interval syndrome were discussed. The study presents also the influence of such
      drugs as amiodarone, sotalol, beta-adrenolytics on QT dispersion. It was found
      out that QT dispersion measurement in patients with cardiac diseases seems to be
      the easy predictor of life-threatening cardiac arrhythmias. The problem is still
      very controversial and needs further clinical investigations.

PMID- 8992541
TI  - [Depression as a complication of stroke].
AB  - Depression remains frequent occurrenced (25-60%) but rare detected and treated
      stroke complication. It may have an essential influence on patients'
      rehabilitation by delaying their time of health remittance. On the basis of
      literature review present prevalence, pathogenesis and phenomenology of the
      poststroke depression. We have also paid attention on so called silent strokes
      role, which may be cause of depression syndromes occurred at elder and pre-elder
      people.

PMID- 8992542
TI  - [Disturbances of water-electrolyte and acid-base balance due to pharmacologic
      treatment of hypertension].
AB  - Antihypertensive drugs may cause serious disturbances of the electrolyte and acid
      base metabolism. On the other hand etiological factors of arterial hypertension
      per se may cause similar abnormalities. These facts possess an essential
      influence on the optimal selection of antihypertensive drugs.

PMID- 8992543
TI  - [Anorexia nervosa and its clinical variations--a hormonal and behavioral
      paradigm].
AB  - The authors presents the regulatory role of endocrine system in children and
      adolescents with anorexia nervosa. The psychological and behavioral symptoms,
      being the main cause of the illness, need a prompt recovery. For that reason, the
      therapeutic activity of psychologist and psychotherapist in the family therapy
      center is fundamental for the patient. Pediatrician's and endocrinologist's task
      is to establish the diagnosis, reinstate the metabolic balance, if need is, and
      prevent the late consequences especially those of reproductive system of the
      patient.

PMID- 8992544
TI  - [Metabolic syndrome X--growth hormone deficiency--controversies].

PMID- 8992546
TI  - [Management of arrhythmias: current trends].

PMID- 8992545
TI  - [Infectious endocarditis: old myths and current concepts].
AB  - Updating of several main themes concerning the infectious endocarditis with the
      aim to denounce various old myths and to precise different actual concepts. The
      authors consider principally the echocardiographic revolution and the new
      diagnostic criteria, the bacteriologic pitfalls and the preventive strategies.

PMID- 8992547
TI  - [Psychosomatic troubles in cardiology].
AB  - Mental stress is a disagreeable feeling accompanied by sympathetic overactivity
      which may mimic heart disorder (panic attack, ...) induce angina pectoris in
      coronary patients or contribute to trigger acute myocardial infarction. It may be
      reproduced by mental stress tests (arithmetic test, ...) and used as diagnostic
      procedure in coronary patients.

PMID- 8992548
TI  - [Biliary ileus].
AB  - A case of gallstone ileus in an elderly woman is described and attention is drawn
      to the insidious clinical presentation and the significance of the often subtle
      radiological signs. The data from the literature specifies these aspects and
      allows a more complete review of this relatively rare pathology in order to
      remind its importance in differential diagnosis to emergency clinicians and
      radiologists.

PMID- 8992549
TI  - [Spontaneous dissection of the internal carotid artery: apropos of a case].
AB  - Dissections of the extracranial internal carotid artery are probably
      underestimated in the general population. They are often unrecognized and
      asymptomatic as shown in this case report and are only the cause of 1 to 4% of
      cerebral ischaemic accidents. However, they are responsible for 5 to 20% of such
      accidents in adults younger than 30 years of age. The nontraumatic nature of the
      carotid artery dissection in our case has been suggested by the medical history
      although minor trauma could have been missed. A skin biopsy has enabled us to
      eliminate elastopathies such as Marfan's or Ehlers-Danlos' syndrome. The
      diagnosis of dissection has been suggested by a Doppler colour echography ; it
      was confirmed by the arteriography which revealed a long dissection looking like
      "string sign" at the level of the internal carotid artery just over the carotid
      bulb. As far as the evolution is concerned, a medical treatment made it quickly
      favourable.

PMID- 8992550
TI  - [Notre Dame a la Rose Hospital of Lessines].
AB  - At the beginning of the 13th century the town of Lessines was an important town
      in Hainaut. In 1243, following the examples of Tournai, Brugge or Brussels, the
      town was equipped with a hospital, 200 years before the building of the hospital
      in Beaune. The hospital was called "Hospital of the Poor" or "Notre-Dame (Our
      Lady) Hospital". At the end of the 19th century its name was changed into "Notre
      Dame a la Rose (Our Lady with the Rose) Hospital". The wards transformed in the
      years 60 in geriatrics were closed down in December 1980, after nearly 750 years
      of service. For the hospital begun than its new life:its complete conversion into
      a museum.

PMID- 8992552
TI  - [Pharma-clinics. How I treat... facial acne].

PMID- 8992551
TI  - [Foreign residency: specialist candidate in the United States].
AB  - Getting into a residency program in the United States remains relatively easy in
      many specialties. General internal medicine, for instance, is now in vogue, and
      the present time is particularly auspicious, since residency positions offered to
      foreign graduates are likely to be reduced in the near future. The process of
      finding a position is described based on a personal experience.

PMID- 8992553
TI  - [Clinical case of the month. Intramural aortic hematoma: an acute special aortic
      dissection].

PMID- 8992554
TI  - [Conversion enzyme inhibitors in myocardial infarct: who, when, how?].

PMID- 8992555
TI  - [Professional risk of viral infections (hepatitis A, B, C and AIDS)].

PMID- 8992556
TI  - [Cutaneous manifestations of diabetes].

PMID- 8992557
TI  - [Role of non-invasive ventilation in internal medicine].

PMID- 8992558
TI  - [Circulatory assistance. II. Complications and results].

PMID- 8992560
TI  - [How I explore.... an adult subject with suspected hypothyroidism].

PMID- 8992559
TI  - [Anti-ganglioside antibodies and peripheral neuropathies].

PMID- 8992561
TI  - [Pharma-clinics. Drug of the month. Tacrine (Cognex)].

PMID- 8992564
TI  - [The general surgeon in the field of specialists].

PMID- 8992563
TI  - [What is your diagnosis? Right ventricular dysplasia].

PMID- 8992562
TI  - [Drug of the month. Maxsoten].

PMID- 8992565
TI  - [Initial results with withdrawal treatments of male and female participants in
      the diversified Janus opiate prescription project in Basel].
AB  - Since the beginning of the 'Janus' opiate project in Basel in which severely
      opiate-dependent persons are treated intravenously with heroin, morphine or
      methadone 11 from 160 participants (to november 1995) were treated in the
      withdrawal and intervention unit at the psychiatry clinic of the university of
      Basel. 7 patients sought a total, 4 a partial withdrawal. Whereas the 4 patients
      wanting withdrawal from consumption of drugs in addition to study drugs all
      reached their goal 4 of the 7 persons aiming at total withdrawal interrupted
      treatment prematurely. The 3 patients who were successful are-as far as the
      authors know-still off opiates. Substitution of intravenous opiates provided by
      'Janus' with oral methadone and slow tapering off of the latter over days to
      weeks occurred mostly without problems. Participants of the 'Janus' project thus
      desired a withdrawal oriented treatment with equal frequency and had not less
      success than persons substituted with oral methadone in achieving this goal.

PMID- 8992566
TI  - [Peak-flow monitoring in asthmatic patients: indications and therapeutic
      implications of the measurements with reference to the 'traffic-light system'].
AB  - Peak flow meters do not allow to perform lung function analysis in the private
      practice. However, they can be used for the diagnosis of reversible airway
      obstruction, to search for exacerbation factors in asthma, and to monitor drug
      therapy in chronic asthma. Peak flow measurements provide the means for self
      assessment and self-management of asthma by the patients themselves allowing
      treatment to be optimized and guaranteeing a better quality of life. The plotting
      of daily pre- and post-bronchodilator peak flow values enables the patient to
      understand the pathophysiologic changes in his respiratory tract. Therapeutic
      implications are easily recognized and can be performed without delay by the
      patient himself on the basis of the so-called "traffic light system".

PMID- 8992567
TI  - [Anticoagulant-induced pseudo-thrombocytopenia: an important laboratory
      artifact].
AB  - In the medical unit of our regional hospital we observed eight cases of
      anticoagulant-related pseudothrombocytopenia within two years. Attention is drawn
      to this often misdiagnosed laboratory artefact. In every unexpected
      thrombocytopenia found by automatic cell-counting a simple blood smear should be
      studied especially for thrombocyte-aggregates and the automatic platelet-count
      should be repeated using another anticoagulant, before other investigations are
      undertaken.

PMID- 8992568
TI  - [Polyneuropathy, diarrhea].
AB  - A 44-year-old patient with 24 kg reduction of body weight within three years due
      to recurrent diarrhea was admitted to the hospital. Physical findings of the
      patient were not remarkable, except for hypesthesia and hypalgesia of the front
      of the tibia and of the lower legs. Laboratory as well as endoscopic and
      functional examinations of the gastrointestinal tract did not reveal any
      remarkable finding. Infectious origins of the disease were excluded. A
      histological examination of a rectum specimen yielded amyloid deposits in the
      submucosa of the rectum. In the family history of the patient, relatives with
      liver and gastrointestinal diseases due to amyloidosis were detected. Amyloid
      deposits and the positive family history of the patient led to the diagnosis of a
      gastrointestinal manifestation of familial amyloidosis.

PMID- 8992569
TI  - [A case from practice (363). Monoarthritis in juvenile chronic arthritis].

PMID- 8992570
TI  - [A case from practice (364)].

PMID- 8992571
TI  - [What is your diagnosis? Arthritis caused by human parvovirus B 19 (HPV B19
      arthritis)].

PMID- 8992572
TI  - [Nutrition for everyone].

PMID- 8992573
TI  - [Nutritional recommendations for diabetic patients: adaptation of the
      recommendations defined by the Diabetes and Nutrition Study Group of EASD].
AB  - Nutritional recommendations for diabetics are nowadays more flexible and better
      adapted to the individual patient. They resemble those offered to the public at
      large. Caloric intake is determined by body size and weight as well as physical
      activity. Approximately 60% of the energy should be consumed in the form of
      carbohydrates and monounsaturated fatty acids. The proportion of fatty acids and
      carbohydrates is fixed according to the individual nutritional habits. The intake
      of saturated and polyunsaturated fatty acids should be restricted. Meals and
      carbohydrates should be distributed over the day as three main meals with two to
      three snacks in between. Recommendations should always be adapted to the
      practical possibilities of the individual and to his particular metabolic
      situation.

PMID- 8992574
TI  - [Diet treatment of obesity--weight-loss stage and weight-maintenance stage].
AB  - Dietetic treatment of obesity occurs in two phases one of weight reduction and
      one of stabilisation of the reduced weight. Results of the first phase are marked
      mainly by reduction of calories (quantitative aspect) and not by the carbohydrate
      or fat content of the diet (qualitative aspect). This improves assessment of
      individual nutritional preferences and sustains the patients motivation longer.
      Current recommendations propose less restrictive diets, i.e. 500 Kcal less than
      the daily allowance. In the second phase of stabilisation a diet rich in complete
      carbohydrates (> 50 of daily calories) and poor in lipids (< 30%) regulates
      metabolism, appetite sencurion of saturation and thermogenesis favorably. Such a
      diet seems to permit a prolonged stabilisation of weight, an important criterion
      for successful treatment of obesity. A diet rich in carbohydrates and poor in
      lipids symbolized by a nutritional pyramid is at the same time the basis for
      actual recommendations for the entire population.

PMID- 8992575
TI  - [Android-type obesity and gynecoid-type obesity].
AB  - There are several types of obesity, and the metabolic conditions associated with
      these phenotypes are also heterogeneous. Obesity of the male (android) type shows
      a dominant visceral and upper thoracic distribution of adipose tissue, whereas in
      the feminine (gynecoid) type adipose tissue is found predominantly in the lower
      part of the body (hips and thighs). Android obesity is clearly a cardiovascular
      risk factor, more so than gynecoid obesity. Hereditary factors contribute
      significantly to the occurrence of this pathology in families, although
      environmental factors play a role in its development. Android obesity is
      associated with metabolic anomalies which also characterize the syndrome X:
      resistance to insulin, arterial hypertension and dyslipidemia. The predisposition
      of individuals with android obesity to become diabetic rests in part on genetic
      and in part on environmental factors. Hyperinsulinemia and a high flux of free
      fatty acids act at the level of liver and endocrine pancreas to increase
      resistance to insulin and to decrease insulin secretion, two determining factors
      for type II diabetes. Other functional anomalies have been involved to explain
      android obesity such as dysregulation of adrenocortical and sexual steroids or a
      global derangement of stress mechanisms. No significant proof, however, seems to
      support either one of these hypotheses.

PMID- 8992576
TI  - [Dietary approach to obesity].
AB  - Dietetic treatment of overweight has its limits in cases with morbid obesity (BMI
      > 40 kg/m2) or with disturbed eating habits (compulsive eating). In these cases
      surgery and cognitive treatment may play a role. Dietetic treatment is often
      sufficient in patients with moderate to severe overweight (BMI > 27 to 39 kg/m3).
      This includes in the first place identification of bad habits by evaluation of
      nutritional behaviour over 3 or 7 days. The most frequent mistakes are the
      jumping of a meal (mostly breakfast) and nibbling of snacks rich in fat between
      meals and omission of hypocaloric and voluminous food like fruit and vegetables.
      The lacking sensation of saturation which is fostered by rapid and automatic food
      intake, may also contribute to the maintenance of overweight. The first dietetic
      rules to be observed consist in a regular schedule for meals and-if necessary
      snacks in between and the selection of a lipid-poor diet with particular
      attention to hidden fat. The meal should be turned into an enjoyable experience
      whenever possible without other concurrent activities.

PMID- 8992577
TI  - [Diet and dyslipidemia].
AB  - In this article recommendations for dyslipidemias are illustrated by practical
      dietary recommendations for an individual patient with combined hyperlipidemia.
      Recommendations in hypercholesterolemia above all consist in the replacement of
      saturated by unsaturated forty acids thus reducing automatically cholesterol,
      too. In hypertriglyceridemias reduction of body weight should often be combined
      with quantitative control of alcohol and simple carbohydrates. A list of foods to
      be chosen or to be avoided is provided.

PMID- 8992578
TI  - [A case from practice (365). Acute schistosomiasis mansoni (Katayama fever)].

PMID- 8992579
TI  - [A case from practice (366). Jellyfish sting--neurotoxic activity on the sensory
      nerves].

PMID- 8992580
TI  - [History of psychiatry and neurosciences in French-speaking Switzerland].

PMID- 8992581
TI  - [Development of psychiatric classifications in Geneva, from the beginning of the
      19th century to today].

PMID- 8992583
TI  - [Occupational therapy in the treatment of the mentally ill. The cantonal asylum
      of Cery (Prilly-Lausanne) 1873-1899)].

PMID- 8992582
TI  - [From lunatics to the mentally ill across the principle of health legislation in
      Vaud (1803-1901)].

PMID- 8992585
TI  - [The eyes and ears of the physician. Psychiatric nurses toward 1930].

PMID- 8992586
TI  - ["The drama of Brenles". Foundations of forensic psychiatry in French-speaking
      Switzerland].

PMID- 8992584
TI  - [Has there been a death at Bel-Air?].

PMID- 8992587
TI  - [French-speaking Switzerland "at the discovery of the unconscious"].

PMID- 8992589
TI  - [Production and exploitation of works of fine arts created in a psychiatric
      facility].

PMID- 8992590
TI  - [Photographic iconography of La Salpetriere].

PMID- 8992591
TI  - [The neuroanatomic melting pot of Lausanne (1973-1993)].

PMID- 8992588
TI  - [From Geneva to Zurich: Jung and French-speaking Switzerland].

PMID- 8992592
TI  - [The disabled conscience].

PMID- 8992593
TI  - [Do you need a transplant?].

PMID- 8992594
TI  - [Heart-lung and lung transplantation].

PMID- 8992595
TI  - [Adrenal transplantation and Parkinson's disease].
AB  - Although substantial therapeutic advances have been developed during the last
      decade, L-dopa remains as the most successful treatment for Parkinson's disease.
      However, about 80% of the patients show motor and psychiatric complications after
      several years of levodopa treatment. Thus, new therapeutic approaches have been
      undertaken during the last decade in order obtain a better control of the motor
      symptoms. Adrenal medullar grafts into caudate nucleus and/or putamen have been
      widely studied as a new therapeutic strategy. They have been undertaken in more
      than 300 parkinsonian patients and the general finding is that adrenal medullar
      grafts induce a significant improvement of motor symptoms which remain 1 year
      after the surgery. The mechanisms by which they can elicit a motor improvement
      are not well understood since chromaffin cells do not survive in the host brain
      after transplantation as demonstrated by PET scan studies. The present work
      summarizes the results found by different authors as well as the mechanisms
      involved in the motor improvement observed in these patients.

PMID- 8992596
TI  - [Technique and function of an experimental multiorgan transplant model in pigs].
AB  - En bloc transplantation of the liver, duodenum and pancreas has been successful
      in humans for the treatment of tumors requiring exenteration of the upper
      abdomen. We have developed an experimental model in 40 pigs of en bloc
      transplantation of the liver, duodenum and pancreas. The surgical technique for
      organ harvesting and preservation has been correct as the early graft function
      was excellent. We describe in detail the surgical technique in the recipient
      animal, the anesthetic model and the autopsy findings. Liver function was
      excellent and endocrine pancreatic function was normal within 8 hours after
      transplantation. Absorption and insulin-secreting response was normal in a few
      animals studied with an oral glucose overdose and with the intravenous glucagon
      test.

PMID- 8992597
TI  - [Pathological anatomy of organ transplantation].
AB  - We review some morphological aspects shared by all allografts. The main points
      are: 1) The expression of antigens of histocompatibility, essentially DR, allows
      the diagnosis of acute rejection with a significant specificity; 2) A lesion
      similar to "Quilty" effect may be seen in other allografts, and it is the first
      manifestation of an acute rejection; 3) Fine-needle aspiration biopsy may help in
      the follow-up of kidney transplant but has been demonstrated ineffective in other
      transplants; 4) The morphology of rejection is different according to the type of
      immunosuppressive therapy; 5) The basic lesions of chronic rejection are
      vascular, but chronic rejection may be diagnosed without vessels in the biopsy
      specimen, by the degree of atrophy of the parenchyma; 6) For the characterization
      of lymphomas in transplanted patients is necessary study the clonality of tumor
      cells, the gene rearrangement and the lymphoid subset; 7) Molecular Pathology may
      help in the early diagnosis of viral infections after transplantation.

PMID- 8992598
TI  - [Prognostic implications of urological complications in the renal
      transplantation].
AB  - We describe the urological complications occurred in 302 patients undergoing
      first cadaveric renal transplantation in 16 years in the University Hospital. two
      series can be distinguished: "Historical" (1976-86) and "Actual" (1986-92).
      Thirty patients (10%) presented 33 (11%) urological complications: 73% urinary
      fistula and 27% ureteral stenosis. The vast majority (80%) were early
      complications (before 90 days). No statistical difference was observed in the
      survival rates of both the patients and grafts presenting or not urinary
      complications, except in the last series. A multivariate analysis was performed
      to examine the influence of prognostic factors. These analysis revealed that cold
      ischemia time and organ retrieval were the technical variables significantly
      related with urologic complications among historical and global series. Only
      recipient age was associated with urologic complications in actual series.

PMID- 8992599
TI  - [Surgical aspects of renal transplantation].
AB  - Expansion of donor criteria and more efficient use of the donor pool are needed
      to address the current organ shortage. Results of renal transplantation in older
      patients support broader recipient selection. To improve intraoperative donor and
      recipient management, and decrease the rate of delayed graft function, and refine
      surgical techniques to address more complicated patients are also attempts to
      expand donor pool. Use of hepatitis-C-positive donors is not safe in hepatitis-C
      positive recipients for non-life-saving organs.

PMID- 8992600
TI  - [Transplantation in orthopedic surgery and traumatology].
AB  - Clinical applications of the musculoskeletal system tissue bank are currently
      enlarging in areas such as tumour surgery, spine surgery and arthrodesis,
      reconstructive procedures of the hip joint and ligament repair. We report our
      experience about the use of more than 1,000 grafts utilize from 1987 to 1992. We
      concluded that a bone bank or a musculoskeletal system tissue bank has a great
      usefulness in different reconstructive surgery technics and arthrodesis. They are
      used more frequently in orthopaedic and traumatology surgery improving the
      development of this surgery.

PMID- 8992602
TI  - [Transplantation ethics: review].

PMID- 8992601
TI  - [Indications for bone marrow transplantation].

PMID- 8992603
TI  - Role of Toxicologic Pathology in advancing understanding of previously identified
      hazards, current safety assessments, and mechanism of action for therapeutic
      xenobiotics.

PMID- 8992604
TI  - The effect of indomethacin administration on the splenic changes induced by
      estradiol supplementation in ovariectomized New Zealand white rabbits.
AB  - In an effort to elucidate the mechanism by which indomethacin (IN) lessens the
      stimulatory effect of estradiol (E2) on rabbit splenic red pulp macrophages
      (RPMs), 39 female New Zealand White rabbits were divided into 10 groups:
      ovariectomized (OVX) and OVX/IN at 0.1 and 5.0 mg/kg body weight (bw)/day; sham
      OVX (SOVX) and SOVX/IN at 0.1 and 5.0 mg/kg bw/day; OVX/25 mg E2 and OVX/25 mg
      E2/IN at 0.1 and 5.0 mg/kg bw/day; and intact control. Changes in RPM population
      in response to treatment were measured using a 0-4 histologic grade. Estradiol
      treatment resulted in increased RPM grade when compared to the OVX groups.
      Indomethacin addition lowered mean RPM grade in the SOVX/IN 5.0 group when
      compared to its E2 control group. Indomethacin administration had no significant
      effect on levels of prostaglandin E2 in spleen, urine, or blood. Hematocrits were
      reduced in both OVX and OVX/E2 groups; this decrease was exacerbated by the high
      IN dose. In summary, the results from this study suggest that the effect of IN on
      E2-induced RPM activation may be mediated through a nonprostaglandin pathway. The
      observed hematocrit changes are possibly the result of direct action of IN and E2
      on erythrocytes, resulting in their accelerated clearance from the circulation by
      splenic RPM.

PMID- 8992605
TI  - Study of the population of enterochromaffin-like cells in mouse gastric mucosa
      after long-term treatment with ebrotidine.
AB  - The possible hyperplastic effect on the mouse gastric mucosa following
      administration of 500 mg/kg of ebrotidine for 18 mo was investigated. The animals
      were taken from the study of carcinogenesis in mouse carried out with this
      product. Two different aspects were considered to assess such a possible
      hyperplastic effect. The height of the fundic and antral mucosa was
      microscopically measured in several points. Histologic sections obtained from
      standardized levels of the stomach were used. The density of argyrophil cells in
      the gastric mucosa has been also quantified, in order to identify
      enterochromaffin-like (ECL) cells, the most abundant among the cells that have
      this property. Grimelius' silver staining method was used to identify ECL cells.
      The cell count was performed under x400 magnification, and the length of mucosa
      examined was determined by computer-assisted image analysis. This study
      complements the mouse carcinogenesis study, in which no differences in tumor
      incidence were found between treated and control animals. The results show that
      administration of 500 mg/kg/day of ebrotidine for 18 mo to mice did not induce
      any hyperplastic effect on the gastric mucosa comprising its various cell types
      or any specific, diffuse, or focal hyperplasia of ECL cells.

PMID- 8992606
TI  - Metabolic and morphometric changes in small and large intestine in rats fed high
      fiber diets.
AB  - Structural modifications of the intestine following fiber intake may play an
      important role in the physiological effects induced by dietary fiber. The aim of
      this study was to examine possible mechanisms for the hypocholesterolemic effects
      of dietary fibers by evaluating both biochemical and morphometric parameters.
      Thirty male Sprague-Dawley rats were divided into 3 groups and fed either a fiber
      free, 15% fiber high methoxy pectin, or 15% cellulose diet for a 4-wk period.
      Plasma cholesterol levels, hepatic enzyme activity, and fecal bile acid excretion
      were determined, and changes in the intestinal structure were evaluated. Daily
      fecal bile acid excretion was significantly higher in rats fed the pectin diet
      accompanied by elevated HMG-CoA reductase activity. Pectin feeding led to
      significant elongation of both the small and large intestine whereas cellulose
      only affected colon length. Computerized image analysis of intestinal cross
      sections showed enlarged muscle area in the ileum and midcolon of pectin-fed rats
      and greater mucosal area in the colon. Circular muscle cell hypertrophy was also
      observed in the colon length. Computerized image analysis of intestinal cross
      sections showed enlarged muscle area in the ileum and midcolon of pectin-fed rats
      and greater mucosal area in the colon. Circular muscle cell hypertrophy was also
      observed in the colon. In contrast, the effects of cellulose feeding were limited
      to elongation of the colon accompanied by muscle cell hypertrophy, and little
      effect on ileal morphology was documented. These data indicate that the
      hypocholestrolemic effects of pectin may be due to increased bile acid secretion
      accompanied by significant morphological changes in the ileum and colon.

PMID- 8992607
TI  - Enhanced arsenite-induced hepatic morphological and biochemical changes in
      phenobarbital-pretreated rats.
AB  - Changes in liver morphology and biochemistry have been assessed 16 hr after a sc
      injection of sodium arsenite [As(III), 75 mumol/kg] to control and phenobarbital
      (PB)-pretreated (80 mg/kg, ip daily for 3 days) adult male Wistar rats. As(III)
      administration to PB-pretreated rats [PB + As(III)] caused hydropic degeneration,
      total loss of glycogen, necrosis in some centrilobular zones, and an increase in
      lipid vacuoles around the periportal area. Electron microscopy showed an
      increased number of vacuoles and autophagosomes containing organelle-like
      material. There was a 30% decrease in total hepatic cytochrome P-450 (CYP450). O
      dealkylation of ethoxy- and pentoxyresorufin and N-demethylation of benzphetamine
      decreased to 42, 32, and 30% of control values, respectively. 5-Aminolevulinic
      acid dehydrase decreased 25% from controls, and metal chelatase activities
      decreased to 25% of the PB-treated group. Injection of As(III) alone resulted in
      a mild increase in lipid-containing vacuoles around the periportal zone, a
      moderate loss of glycogen in midzonal areas, and, by electron microscopy, a
      dilatation of the bile canaliculi and an increase of the number of myelin-like
      structures. CYP450 content and the O-dealkylation of ethoxy- and pentoxyresorufin
      and N-demethylation of benzphetamine all decreased between 30 and 50%. These
      results demonstrate the greater susceptibility of the liver to injury following
      PB with compounds not requiring metabolic activation. The metabolic basis of
      these changes are unclear but may result from an increased demand for metabolic
      energy due to PB induction and decreased adenosine triphosphate synthesis caused
      by arsenic.

PMID- 8992608
TI  - Histopathology of acetaminophen-induced liver changes: role of interleukin 1
      alpha and tumor necrosis factor alpha.
AB  - Administration of 500 mg/kg acetaminophen (APAP) to female B6C3F1 mice resulted
      in well-documented pathophysiological changes in the liver manifested as
      increased serum concentration of liver enzymes (aspartate aminotransferase,
      alanine aminotransferase, lactate dehydrogenase, and serum sorbitol
      dehydrogenase), centrilobular congestion, and hepatocellular degeneration and
      necrosis. The role of proinflammatory cytokines, including tumor necrosis factor
      alpha (TNF-alpha) and interleukin 1 alpha (IL-1 alpha), on the hepatotoxicity of
      APAP was examined at 4, 8, 12, and 24 hr following APAP administration.
      Neutralization of TNF-alpha or IL-1 alpha with specific antibodies partially
      prevented the hepatotoxic effects of APAP at the 4- and 8-hr time points. In
      addition, prior administration of anti-TNF-alpha antibodies shortened the
      recovery time following APAP treatment. While IL-1 receptor antagonist (IL-1ra)
      had only a modest protective effect against APAP-induced liver damage, as
      determined by serum enzyme release, IL-1ra had no effect on the degree of hepatic
      congestion or necrosis at any of the time points examined. On the other hand,
      administration of antibodies against IL-1ra exacerbated APAP-induced liver
      toxicity. These results suggest that TNF-alpha and IL-1 alpha play an important
      role in the degree of damage and recovery that the liver undergoes following APAP
      intoxication.

PMID- 8992609
TI  - Early histopathologic and ultrastructural changes in the heart of Sprague-Dawley
      rats following administration of soman.
AB  - Male Sprague-Dawley rats were given atropine methylnitrate (20 mg/kg) and HI-6
      (125 mg/kg) ip 10 min before a single injection of 130 micrograms soman/kg sc,
      and the heart was examined by light and electron microscopy 10, 25, 45, 90, and
      180 min after the onset of seizures. Seizures appeared within 6-11 min after
      treatment. Control rats were given saline sc in place of soman. Early myocardial
      lesions consisting of hypercontraction and hyperextension of sarcomeres, focal
      myocytolysis, and contraction bands were detected in individual or groups of
      myocardial fibers. Hypercontraction was characterized by shortening of the
      sarcomere length, disappearance of the I and H bands, and thickening of the Z
      line. In contrast, hyperextended sarcomeres had thickened I and H bands.
      Myocytolysis was characterized by a progressively severe focal dissolution of
      myofilaments and edema of the affected sarcoplasmic area. Contraction bands
      appeared to result from the breakdown of markedly hypercontracted myofibril
      bundles. Due to the presence of a number of surviving myofilaments and the
      preservation of the sarcolemmal tube, distortion of the overall myocytic
      structure was minimal. Changes in the mitochondria and other intracellular
      organelles were also minimal and nonspecific. The close resemblance of
      morphologic findings to those induced by catecholamines supports the view that
      soman-induced myocardial damage is secondary to a treatment-related release of
      unphysiologic amounts of endogenous catecholamines.

PMID- 8992610
TI  - Immunohistochemical study of rat renal interstitial fibrosis induced by repeated
      injection of cisplatin, with special reference to the kinetics of macrophages and
      myofibroblasts.
AB  - Progressive renal interstitial fibrosis occurs following tissue injury, resulting
      in chronic renal failure. In the fibrogenesis, macrophages are speculated to
      induce myofibroblasts producing matrix protein. The kinetics of these cells in
      renal fibrosis induced in rats by repeated injection of cisplatin (CDDP) (2 mg/kg
      body weight, once weekly) was investigated immunohistochemically. During the 10
      wk injection period, epithelial damage of the proximal renal tubules in the
      corticomedullary junction was seen, followed by cystic dilation of the affected
      tubules. During the 8-wk recovery period following the seventh injection, the
      size of the dilated lumina was diminished and atrophic tubules lined by
      regenerating epithelial cells appeared. Morphometrical analysis revealed that
      fibrosis began to develop around the dilated renal tubules in the injection
      period and was more advanced in the following recovery period. Coinciding with
      development of fibrotic tissues, the number of alpha-smooth muscle actin-positive
      myofibroblasts was significantly increased in the areas compared to that of
      controls. In the injection period, despite a significant increase in
      myofibroblast number, an elevation of ED-1 (primary antibody)-positive macrophage
      number was not observed. In the recovery period, however, a significant elevation
      of macrophage number was noticed in markedly advanced interstitial fibrosis. This
      suggests that rapid expansion of the macrophage population, probably resulting
      from release from myelosuppression due to CDDP, might contribute in part to
      development of myofibroblasts, leading to the augmented fibrosis in the recovery
      period.

PMID- 8992611
TI  - Effects found in a one-year oral toxicity study in Sprague-Dawley rats of a novel
      5-HT1A receptor partial agonist for the treatment of anxiety in humans.
AB  - A potent and selective serotonin (5-HT1A) partial agonist with potential as a
      human anxiolytic drug was given in oral doses of 0, 5, 15, or 50 mg/kg/day by
      gavage to Sprague-Dawley rats for 6 or 12 mo. Some animals were allowed 1 mo to
      recover after each treatment period. The 10-fold increase in dose resulted in a
      20-fold increase in drug plasma concentration due to saturable first-pass
      metabolism. This resulted in disproportionately higher concentrations and greater
      bioavailability of the 15- and 50-mg/kg/day regimens. Drug exposure was
      associated with decreased spontaneous activity in the 15- and 50-mg/kg rats. The
      activity of these rats returned to normal during the recovery period. There were
      significant (p < 0.05) decreases in mean body weights during the study for 50
      mg/kg males, with improvement during the recovery periods. No biologically
      significant effects were noted in clinical laboratory parameters. Based on organ
      weight increases and histopathological evaluation, drug-related effects after 6
      and 12 mo of treatment were in the pituitary (both sexes) and all treated female
      reproductive organs. In general, these effects persisted into periods of
      recovery, except for pituitary hyperplasia, which was not apparent following
      recovery after treatment for 6 mo. After treatment for 12 mo and the following
      recovery, there were significant increases in adrenal weights in the 15- and 50
      mg/kg/day males with no morphological correlate. There was increased pituitary
      hyperplasia that persisted through the recovery period in all treated groups in
      both sexes, but there was no increase in pituitary neoplasms. In treated females,
      there was also morphologic evidence of persistent diestrus (estrogenic effect)
      evidenced by endometrial squamous metaplasia, increased corpora lutea, vaginal
      mucification, and decreased uterine size. The clinical and pathological changes
      seen with these 2 regimens were considered exaggerated pharmacological effects of
      the drug on serotonin receptor-rich organs.

PMID- 8992613
TI  - Lipidosis induced in the dog gallbladder by a direct 5-lipoxygenase inhibitor.
AB  - The direct 5-lipoxygenase inhibitor L-739,010 was administered at a dose of 60
      mg/kg/day per os to beagle dogs for 15 days. Histopathological examination of
      gallbladders from treated dogs showed epithelial vacuolation and submucosal
      infiltration by foamy macrophages that were positive for lipids in Sudan Black
      and/or Oil Red O-stained sections. Scanning electron microscopic examination of
      gallbladder mucosa showed thickening of epithelial folds and multifocal
      epithelial membrane disruptions. Transmission electron microscopy confirmed these
      findings and showed mucosal epithelial cell lipid droplet accumulation and
      submucosal infiltration of macrophages filled with lipid droplets, myelin
      figures, heterophagosomes, and cholesterol clefts. These changes resembled those
      reportedly seen in the human gallbladder with cholesterolosis and/or chronic
      cholecystitis.

PMID- 8992612
TI  - Ninety-day feeding study in Fischer-344 rats of highly refined petroleum-derived
      food-grade white oils and waxes.
AB  - Subchronic 90-day feeding studies were conducted in male and female Fischer-344
      (F-344) rats on highly refined white mineral oils and waxes representative of
      those used for food applications. The goal was to help clarify the mixed results
      found in other toxicity studies with laboratory animals. Seven white oils and 5
      waxes were fed at dietary doses of 20,000, 2,000, 200, and 20 ppm and compared
      with control groups on untreated diet; toxicity was assessed at 90 days and also
      after a reversal period of 28 days and/or 85 days. Higher molecular-sized
      hydrocarbons (microcrystalline waxes and the higher viscosity oils) were without
      biological effects. Paraffin waxes and low- to midviscosity oils produced
      biological effects that were inversely related to molecular weight, viscosity,
      and melting point; oil type and processing did not appear to be determinants.
      Biological effects were more pronounced in females than in males. Effects
      occurred mainly in the liver and mesenteric lymph nodes and included increased
      organ weights, microscopic inflammatory changes, and evidence for the presence of
      saturated mineral hydrocarbons in affected tissues. Inflammation of the cardiac
      mitral valve was also observed at high doses in rats treated with paraffin waxes.
      Further studies are required to elucidate the mechanism for the responses
      observed and the relevance of these inflammatory responses in the F-344 rat to
      other species, including humans.

PMID- 8992614
TI  - Chemicals associated with decreases in the incidence of mononuclear cell leukemia
      in the Fischer rat.
AB  - A significant treatment-related decrease in the incidence of mononuclear cell
      leukemia (MCL) was identified in Fischer-344/N rats for 20 chemicals tested in
      the National Toxicology Program's 2-yr carcinogenicity bioassay. Fourteen of the
      20 chemicals caused decreases of MCL in both male and female rats; 6 of the 20
      caused a significant decrease only in males and a marginal or no decrease in
      female rats. Seventeen of the chemicals associated with a decrease in MCL had a
      free aromatic amine or nitro functional groups that could be metabolized to free
      amines. With 1 exception, all 14 chemicals causing a decrease in MCL in both
      sexes produced spleen toxicity in the 13-wk studies. Reduced body weight and
      decreased survival, related either to toxicity or to an increase in other types
      of lethal neoplasms, did not contribute to the decreases in MCL observed in
      chemical exposure groups. Thirteen of the 20 chemicals were positive in
      Salmonella tests, and 15 were associated with increases in neoplasms at other
      sites in rats and/or mice, suggesting that different metabolites could be
      responsible for these varied biological effects.

PMID- 8992615
TI  - Proliferative bone lesions in rats fed a diet containing glucocorticoid for up to
      two years.
AB  - A glucocorticoid was fed in the diet to 50 Sprague-Dawley rats/sex at 0, 0.03,
      0.06, 0.12, 0.25, 0.50, and 1.0 mg/kg/day for up to 2 yr. A total of 1,400 rats
      were examined. Bone neoplasms (5 osteosarcomas and 2 osteomas), involving the
      head, occurred in 7 males that were fed the test compound at the highest dose
      (0.25 mg/kg) with long-term survivors. One osteoma and 1 hyperostotic lesion were
      seen in 2 males receiving lower doses (0.06 mg/kg and 0.12 mg/kg, respectively);
      1 female rat that received the highest dose (1 mg/kg) had an osteosarcoma. The
      results suggest, but do not confirm, a relationship between glucocorticoid
      exposure and bone proliferations in male Sprague-Dawley rats. Other proliferative
      bone lesions included hyperostosis in a 0.12-mg/kg male, osteoma in a 0.06-mg/kg
      male, and osteosarcoma in 1 female at 1.0 mg/kg. The purpose of this report is to
      characterize the incidence and morphology of primary bone proliferative lesions
      found in rats of 1-yr glucocorticoid toxicity and 2-yr carcinogenicity studies
      conducted in our laboratory.

PMID- 8992617
TI  - An epithelioid cell type of amelanotic melanoma of the pinna in a Fischer-344
      rat: a case report.
AB  - An epithelioid cell type of spontaneous amelanotic melanoma in the pinna of an
      aged albino Fischer-344 (F-344) rat is described. When the rat was necropsied at
      109 wk of age, the pinnal tumor was recognized as a white spherical mass of 4 mm
      in diameter. Histologically, the tumor was observed in the dermis and composed of
      large round or polyhedral epithelioid eosinophilic cells that were arranged in
      various-sized cell nests. Immunohistochemistry demonstrated that the tumor cells
      were positive for S-100 protein and vimentin but negative for keratin and a rat
      macrophage antigen. Ultrastructurally, a few single membrane-bound premelanosomes
      that were accompanied by many primary lysosome-like bodies containing very fine
      granules were present in the cytoplasm of the tumor cells. This study has
      disclosed that, in addition to spindle cell variants of amelanotic melanomas, an
      epithelioid cell type of amelanotic melanoma may occur spontaneously in the skin
      of F-344 rats.

PMID- 8992616
TI  - Extensive handling of rats leads to mild urinary bladder hyperplasia.
AB  - The urinary and urothelial effects of the frequent handling necessary for
      obtaining fresh-voided urine specimens were evaluated in 5-wk-old male F-344 rats
      fed control diet or diet containing 7.5% sodium saccharin. Frequent handling
      consisted of holding rats by the back of the neck in a position to obtain fresh
      voided urine directly into centrifuge tubes 3 times per week for 10 weeks,
      whereas seldomly handled control rats received this treatment only twice during
      the entire 10 weeks. The urothelium of frequently handled rats fed control diet
      showed superficial necrosis and regenerative hyperplasia as observed by light and
      scanning electron microscopy. These changes were not observed in rats fed control
      diet that were seldomly handled. The necrosis and hyperplasia were not as
      pronounced in frequently handled rats fed control diet as in seldomly handled,
      sodium-saccharin-treated rats, but handling also potentiated the severity of the
      changes produced by sodium saccharin feeding. The urothelial exfoliation and
      consequent regenerative hyperplasia are likely secondary effects of stress.

PMID- 8992618
TI  - Training in veterinary toxicologic pathology. American College of Veterinary
      Pathologists.

PMID- 8992619
TI  - Proceedings of the 15th International Symposium on Blood Gases and Electrolytes.
      Linkoping, Sweden, May 20-23, 1994.

PMID- 8992620
TI  - [Regulation of leukocyte migration by adhesion molecules].
AB  - The ability of leukocytes to leave the blood-stream and migrate into tissues is a
      critical feature of the immune system, essential in eliminating infectious
      pathogens and allowing leukocyte accumulation at sites of injury, infection or
      inflammation. Lymphocytes continuously recirculate between tissues, lymphoid
      organs and blood, whereas neutrophils or monocytes lack this capacity. Migration
      of various leukocyte subpopulations into tissues is regulated by specific
      combinations of adhesion receptors and chemoattractants which direct them into
      tissues. Selectins initiate leukocyte attachment along vascular endothelium by
      mediating leukocyte rolling along inflamed endothelium, whereas CD11/CD18 (alpha
      L, M, X/beta 2) integrins have a more important role in subsequent steps of
      leukocyte migration into tissues. alpha 4/beta 1 or alpha 4/beta 7 integrins play
      a role in mediating lymphocyte rolling and firm adhesion to vascular wall.
      Leukocyte migration is an important mechanism in the pathogenesis of inflammatory
      diseases, the regulation of hematopoiesis and hemostasis. This reaction is also
      involved in the pathogenesis of atherosclerosis, reperfusion injuries and
      malignant cell metastasis. Leukocyte migration inhibitors may have therapeutic
      potential against inflammation and associated diseases.

PMID- 8992621
TI  - [Reactive thrombocytosis, a lipid dysfunction?].
AB  - Reactive thrombocytosis (RT, platelet counts > 400 x 10(3)/mm3) following
      coronary artery bypass grafting (CABG) has previously been reported to occur
      frequently (20%) and is associated with thrombotic complications, e.g. vein graft
      occlusion. This prospective study was undertaken in an attempt to identify the
      underlying causes of RT following CABG. 40 consecutive patients undergoing
      elective CABG entered the study between December 1 1994 and April 15 1995.
      Patient characteristics, operation data, cardiopulmonary data and postoperative
      complications (30 parameters) were evaluated together with routine blood
      chemistry, hematology, hemostasis and anti-inflammatory parameters (25
      parameters/ day, preoperatively until the 9th postoperative day). 15 patients
      developed RT and 25 served as controls. Patient characteristics did not differ.
      Operation data, cardiopulmonary bypass data and post-operative complications
      revealed no group differences, neither did preoperative laboratory results,
      except that S-cholesterol was higher in the RT-group (6.2 +/- 0.9 vs. 5.3 +/-
      0.9, p < 0.018). All blood findings were without group differences throughout the
      entire study period, except platelet counts, platelet size (PWD) and mean
      platelet volume (MPV), and AT III levels on the 7th postoperative day, which were
      significantly lower in controls compared to RT. RT patients had a less marked
      drop in platelet count immediately after cardiopulmonary bypass than non-RT,
      together with an increased MPV, but without differences in PWD. There was a
      significantly higher platelet count in the RT group on the 3rd postoperative day,
      which remained higher throughout the study period. This study has again found RT
      frequently occurring after CABG (30%). Preoperative S-cholesterol was
      significantly higher in the RT group, while other parameters did not differ in RT
      vs. non-RT. It is therefore possible that RT is linked to a lipid dysfunction,
      and further studies are ongoing.

PMID- 8992622
TI  - [Effect of postoperative retransfusion of autologous blood products on hemostasis
      in heart surgery].
AB  - In cardiac surgery a reduction of homologous blood products is mainly achieved by
      autologous blood salvage. Unprocessed retransfusion of autologous blood may
      induce changes in hemostasis. We assessed changes of activated clotting times
      (ACT) after retransfusion of unprocessed (1) oxygenator blood and (2) shed
      mediastinal blood. In 41 patients undergoing cardiac surgery (37
      revascularization and 4 valve procedures) with a mean cardiopulmonary bypass time
      of 116.3 min, ACT was measured at the following time points: pre- and
      postoperatively, and before and after retransfusion of oxygenator blood and shed
      mediastinal blood. A significant prolongation of ACT values was only seen between
      pre- to postoperative blood (p < 0.003). Retransfusion of oxygenator blood
      changed ACT from 120 +/- 25 vs 116 +/- 17 sec and retransfusion of shed
      mediastinal blood showed a mean ACT of 118 +/- 14 vs 115 +/- 20 sec from before
      to after transfusion. There was a significant correlation between the ACT value
      in the unprocessed oxygenator blood and the ACT value measured in the patient
      after retransfusion (r = 0.41, p < 0.02). 6 patients receiving over 1 litre of
      unprocessed autologous blood (either from the oxygenator or the mediastinum) in
      less than 60 minutes showed a significant increase of ACT value after transfusion
      (p < 0.05). Hence, under normal conditions, retransfusion of unprocessed
      autologous blood will not significantly alter hemostasis measured by the ACT test
      in patients undergoing cardiac surgery.

PMID- 8992623
TI  - [Type and Screen: immunohematological safety is ensured and costs are lowered].
AB  - TYPE AND SCREEN: (T + S) means: no routine cross match before transfusion. ABO-
      and Rh-(Blgr) blood groups (type) are done and irregular allo-antibodies are
      sought (screen). If screen is negative, instant saline test (IST) or Blgr
      control, and if screen is positive, conventional cross match is done. GOALS: Are
      all clinically relevant antibodies discovered with T + S? Are laboratory costs
      lower? METHODS AND STUDY DESIGN: Prospective study over more than 3 years. Blgr
      and cross match were done in tubes and AB screen and antibody identification
      (panel) were sought using the gel-test (DiaMed) with bromelin (enz) and LISS
      antiglobulin test (IAT). Underlying all testing were the directives of the Swiss
      blood donation services. RESULTS: Enzyme-only positive antibodies are not
      relevant for blood transfusion, as shown by our data from more than 10000
      comparisons of enz- and IAT-screens. 32 patients with positive enz-antibodies and
      negative cross match were transfused without problems. The enz-screen was
      abandoned for more than 12 months' follow-up in more than 20000 transfused
      patients. Before using the T + S, one unit of transfused RBC needed (on average)
      3.7 cross matches, and after introduction of T + S only 0.3. Although the number
      of T + S increased significantly, we effectively saved some CHF 280000 per year.

PMID- 8992624
TI  - [Breast carcinoma: state of the art].
AB  - Diagnosis and therapy of breast cancer are briefly reviewed for the general
      internist. He should know what triple diagnosis, breast-conserving surgery,
      radiotherapy and adjuvant systemic therapy involve. He should know when to
      perform a screening mammography, what follow-up examinations after breast cancer
      are indicated and what dangers loom in metastatic breast cancer. He should know
      of new therapeutic avenues such as bisphosphonates, new aromatase inhibitors,
      taxanes, and high-dose chemotherapy with stem cell support. Since advances in the
      treatment of breast cancer have been achieved mostly through randomized studies,
      a positive attitude toward such studies and a willingness to take part in them
      are desirable.

PMID- 8992625
TI  - [Tuberculosis therapy in canton Zurich 1991-1993: what are the causes for
      recurrence and therapy failure?].
AB  - A retrospective cohort analysis of TB patients in the Canton of Zurich was
      undertaken to evaluate the effectiveness of a primary care physician-based
      tuberculosis treatment program in the Canton of Zurich (1991-1993) and compare it
      with treatment results in selected patient groups in controlled prospective
      studies. Of the 440 TB patients (62.5% men, 51% foreign born, 9.6% with HIV
      infection) 65% were initially hospitalized. The total treatment duration was 210
      (+/-108) days on average. Only 75% of the patients who were treated by a total of
      410 hospital and primary care physicians were treated with standard regimens
      according to guidelines. 3 patients were treatment failures; 13 relapsed (5.1% of
      the 257 patients reexamined in 1995). Possible causes for relapses were poor
      patient compliance due to alcoholism, homelessness, drug addiction, psychiatric
      disorders; prescription errors with inadequate treatment durations, concurrent
      AIDS disease, or use of a three-drug combination despite primary drug resistance.
      In 4 of the relapse patients and in all 3 treatment failures, secondary drug
      resistance developed under treatment. 5 of these 7 patients were treated
      initially only with a fixed three-drug regimen (Rifater). The relatively high INH
      resistance rate (8.6%) and relapse rate (5.1%) in the Canton of Zurich renders
      the use of a four-drug combination therapy necessary. In the outpatient
      maintenance phase, more effort must be devoted to ensuring patient compliance and
      adherence to a proper treatment duration. This should be documented by a
      standardized questionnaire at 6 or 12 months after initiation of therapy. In high
      risk patients in particular, home care visits by a TB nurse in addition to
      consultations by primary care physicians are necessary to ensure directly
      observed therapy (DOT) in order to prevent relapses and treatment failures.

PMID- 8992626
TI  - [Extrapulmonary infections with Mycobacterium tuberculosis complex].
AB  - In a retrospective study we reviewed all records of patients with newly diagnosed
      Mycobacterium tuberculosis complex infection during the years 1990-1994. Of the
      45 patients identified, 27 (60%) had only pulmonary tuberculosis and 18 (40%) had
      extrapulmonary tuberculosis with (5 patients, 11%) or without (13 patients, 18%)
      concomitant pulmonary infection. The extrapulmonary manifestations were as
      follows: miliary 5, joint 3, meningeal 2, pleural 2, kidney 1, peritoneal 1, bone
      1, psoas 1, lymphatic 1, and anal 1. In the 18 patients with extrapulmonary
      tuberculosis the infection was due to Mycobacterium tuberculosis 14 times,
      Mycobacterium bovis twice, and Mycobacterium bovis BCG once.

PMID- 8992627
TI  - [Development of early-summer meningoencephalitis (FSME) in the Thurgau region
      1990-1995--a new endemic area?].
AB  - Tick-borne encephalitis (TBE) is a viral infection transmitted by bites of
      infected ticks. The clinical course is mostly mild, but death occurs in 1-2% of
      TBE infections and nearly half of patients with meningitis/meningoencephalitis
      show residual disease, above all chronic headache. TBE-infected ticks occur only
      in endemic areas. A knowledge of the endemic areas is very important for
      immunoprophylaxis of TBE. In recent years between 26 and 97 cases of TBE have
      occurred in Switzerland. The largest endemic areas are in Canton Schaffhausen,
      the northern part of Canton Zurich and the north-west of Canton Thurgau. Another
      endemic area is known in the region of Thun in Canton Berne. Another possible
      endemic area is known in the Zurich Oberland around Elgg, only 7 km from Aadorf
      in Thurgau. Up to now, Diessenhofen in the north-west of Thurgau was the only
      known possible endemic area. In 1994 and 1995 we observed an accumulation of TBE
      infections in western Thurgau. The question was whether there are other endemic
      areas in Thurgau. In this retrospective analysis we studied the TBE cases in
      Thurgau between 1990 and 1995 with data derived from the cantonal health
      authorities reports. Clinical data were taken from case histories of the two
      cantonal hospitals in Frauenfeld and Munsterlingen, completed by data from family
      doctors and patients. Between 1990 and 1995 30 TBE infections (1990; 1, 1991: 4,
      1992: 3, 1993: 1, 1994: 4 certain, 3 uncertain, 1995: 14) were observed. TBE
      infections appeared between May and October (maximum in May). 14 patients
      remembered a bite by a tick several weeks before onset of the illness. 7 bites
      occurred in the area of Frauenfeld/Aadorf. Only one bite occurred in
      Diessenhofen. 2 patients were infected in well-known endemic areas in Canton
      Zurich, a vicinal region in the west of Thurgau. In 1995 the incidence of TBE in
      Thurgau was 5.4/100000 population. In 9 of the 14 patients recalling a bite by a
      tick (64.4%), the bites occurred near their domicile. No bite was seen east of a
      line between Steckborn and Weinfelden. The incidence of TBE in Thurgau in 1995
      was clearly higher than the average in Switzerland in recent years (0.46/100000),
      and higher than in the well-known endemic areas in the vicinity (Schaffhausen
      3.95, Zurich 1.31). Based on our data, the region Frauenfeld/Aadorf must be
      declared a new endemic area for TBE. Probably the well-known endemic area in the
      Zurich Oberland in the vicinity of Elgg has spread eastward. Persons who are
      often in the forests of this region should be advised to be vaccinated.

PMID- 8992628
TI  - [Modifiability of antibiotic use in a medical clinic].
AB  - The most costly drug interventions in hospitals are in the treatment of
      infectious diseases. To improve the cost-effective use of antibiotic drugs it is
      necessary to consider rational indications, appropriate administration
      (sequential therapy) and control of antimicrobial resistance. To obtain more
      information about prescribing habits, antibiotic prescription forms were
      collected prospectively over a six-month period in the Clinic of Internal
      Medicine at the Cantonal Hospital of Aarau. The influence of this new
      prescription form on antibiotic use, including the indication for therapy, was
      analyzed and compared with the results of a similar study done in 1994. The
      results showed use of a wide variety of different antibiotics for the same
      indication, prevalence of intravenous administration, and widespread use of new
      and expensive antibiotics. The total cost of antibiotics was not reduced compared
      with the previous period. The characteristics of antibiotic use were easily
      analyzed with minimal additional effort. With such data, specific actions for
      quality improvement in antibiotic use can be taken through a multidisciplinary
      educational approach with regular instruction on therapy guidelines, definition
      of first-line agents, information on the advantages of sequential therapy, and
      periodic reevaluation.

PMID- 8992629
TI  - [Vaccination in elderly patients in rehabilitation: a missed opportunity?].
AB  - BACKGROUND: Immunization against influenza is recommended for elderly persons in
      Switzerland, but no national guidelines are currently available regarding
      immunization of the elderly against pneumococcus and tetanus. In addition, almost
      no data are available regarding immunization rates of the elderly in the general
      population. In this study we explored the immunization status for influenza,
      tetanus and pneumococcus of a selected elderly population admitted to a Swiss
      rehabilitation facility. POPULATION AND METHODS: The study population (n = 145)
      were patients admitted to a rehab facility during 3 consecutive winter months.
      Data on demographics, immunization, previous functional status (BADL, IADL),
      cognitive (MMSE) and affective status (GDS) were collected upon admission.
      RESULTS: Subjects' mean age was 79.4 years, 32.4% were male, 42.8% had BADLs
      dependencies and 81.9% IADLs dependencies. Most patients had normal MMSE and GDS
      scores. Vaccination rates were 39.3% for influenza, 12.4% for tetanus and only
      2.1% for pneumococcus. In univariate analyses, people immunized against influenza
      were older than those who were not (p = 0.01). This relationship remained in
      multivariate analyses, controlling for gender, functional, cognitive and
      affective status. Subjects aged 80 and over were 2.5 times (95% CI 1.2-5.5, p =
      0.02) more likely to be immunized against influenza, but were less likely to be
      immunized against tetanus (OR 0.3, 95% CI 0.1-0.9, p = 0.04). Functional status
      was not significantly associated with any vaccination status. CONCLUSIONS:
      Immunization rate for influenza in this selected population is similar to those
      described in US surveys. The positive association between older age and flu
      vaccination is surprising and needs further investigation. These results also
      indicate a need to educate patients and physicians in order to increase
      vaccination use, especially against pneumococcus.

PMID- 8992630
TI  - [Nonbacterial thrombotic endocarditis: a contribution to the clinical
      differential diagnosis in culture-negative endocarditis].
AB  - Nonbacterial thrombotic endocarditis is rarely diagnosed before death. We report
      on 3 patients with nonbacterial thrombotic endocarditis to illustrate the
      clinical course of this disease that can cause severe systemic thromboembolism
      and may be the first manifestation of malignant disease. Nonbacterial thrombotic
      endocarditis must be considered in the differential diagnosis of culture-negative
      endocarditis.

PMID- 8992631
TI  - [The absence of autoantibodies does not rule out autoimmune hepatitis].
AB  - The diagnosis of autoimmune hepatitis is mainly based on the finding of
      characteristic autoantibodies. Untreated patients have a poor prognosis because
      of rapid development of cirrhosis. Immunosuppressive treatment most often leads
      to remission. We report on 2 female patients aged 44 and 53 with autoimmune
      hepatitis. Initially no significant titers of autoantibodies against nuclear,
      cytosolic or microsomal components of the hepatocyte could be demonstrated.
      Seropositivity for autoantibodies was demonstrated 6 and 8 weeks later in the
      course. Immunosuppressive therapy with steroids resulted in rapid decrease of
      transaminases with persistent remission of autoimmune hepatitis. CONCLUSION:
      seropositivity for characteristic autoantibodies is not an absolute criterion for
      the diagnosis of autoimmune hepatitis. Patients with hepatitis of unknown origin
      should therefore be given a steroid treatment trial.

PMID- 8992632
TI  - [Drug-induced hepatic involvement, something to consider!].
AB  - A retrospective study over the last 5 years on drug-induced liver injury was
      performed in the Internal Medicine Department of the University Hospital of
      Geneva. According to WHO and Council for International Organizations of Medical
      Sciences (CIOMS) criteria for drug-induced liver adverse events, 142 cases were
      identified, with 255 drugs fulfilling causality criteria of certain, probable or
      possible. 63 patients (44%) suffered severe consequences of liver injury,
      including 9 deaths. Drugs reported belonged to the therapeutic classes of
      antibiotics (43%), cardiovascular (20%), analgesics (10%), gastrointestinal (9%),
      psychotropic (7%), and others (11%). Despite bias inherent to the retrospective
      methodology, only 10% of the side effects were spontaneously reported to the
      pharmaco-vigilance board. This is in accordance with the known reporting rate. It
      can be concluded that spontaneous reports are to be regarded only as signals.

PMID- 8992633
TI  - [Medical-ethical guidelines for organ transplantation. Swiss Academy of Medical
      Sciences].

PMID- 8992634
TI  - [Hyperbaric oxygenation (HBO) in the treatment of radiogenic side effects].
AB  - AIM: Many reports show that late complications of radiotherapy can be
      successfully treated by hyperbaric oxygen (HBO). This synopsis attempts to review
      the literature to identify areas of clinical use and further research. PATIENTS
      AND METHODS: Clinical and experimental data about HBO treatment of radiation late
      effects are analysed. Mechanisms of hyperbaric oxygen in the treatment of late
      radiation side effects are discussed. RESULTS: There is evidence in the
      literature that HBO is beneficial in the treatment of radiation cystitis,
      osteoradionecrosis of the mandible, hemorrhagic proctitis, soft tissue necrosis
      and neurologic deficits. The prophylactic use of HBO has shown to prevent the
      development of osteoradionecrosis after tooth removal and the loss of titanium
      implants in irradiated facial bones. The physiologic basis of HBO can be referred
      to induction of neoangiogenesis and revascularisation. CONCLUSIONS: Clinicians
      can be encouraged to use hyperbaric oxygen for the treatment of radiation
      cystitis, osteonecrosis of the mandible, hemorrhagic proctitis, soft tissue
      necrosis and neurologic deficits following radiation therapy.

PMID- 8992635
TI  - [Radiotherapy in northern Germany: data on radio-oncology from 6 Bundeslander].
AB  - BACKGROUND: Facts and figures about German radio-oncologic centers are scarcely
      available. A first glance was made possible by the accumulation of data published
      by the German Rontgen Society ("Abteilungen und Praxen fur Strahlentherapie in
      der Bundesrepublik Deutschland, 1994"[4]). Detailed and up-to-date information is
      difficult to collect from the whole Federal Republic. Therefore, a regional data
      base limited to the 6 northern German states was created in order to get correct,
      detailed and current facts and figures from radio-oncologic departments of this
      region. PATIENTS AND METHOD: Traditionally there was a close cooperation between
      the Rontgen Society of Northern Germany and the Society of "Niedersachsen" and
      "Sachsen-Anhalt". Therefore, hospital departments and free standing office-type
      facilities in radio-oncology from 6 states have put together a regional North
      German data-base. Detailed questionnaires were sent out in order to get data on
      heads of departments, professional staff, technical equipment, workload,
      diagnoses and training facilities. The collected data were distributed to all
      participating centers for confidential individual analysis. This paper reports
      the data collected. RESULTS: The survey 1995/96 had an unexpected return. Thirty
      six from 38 centers in a region with 17.36 million inhabitants in 6 states (21.3%
      of Germany) took part. There were 73 megavolt machines and 31 afterloading
      facilities. Two hundred and forty physicians, 110 physicists, and 350
      radiographers were working in radio-oncology; and there were 852 hospital beds
      specifically assigned to radio-oncology for the care of in-patients. In 1995,
      32,000 patients were treated with 37,000 series, 570,000 treatment visits and
      1,600,000 radiation fields. The average patient got 1.2 series, 18 treatment
      visits and 50 fields. Equipment-wise, an average department runs a mean of 2
      megavolt machines and 1 afterloading facility. The corresponding data for 1
      megavolt machine were 3.5 physicians, 1.6 physicists, 5 radiographers and 13
      hospital beds. There was 1 machine for 240,000 inhabitants. The average workload
      of a megavolt machine was 439 patients a year with 513 series, 7,813 treatment
      visits and 21,845 radiation fields. CONCLUSIONS: A regional data-base for radio
      oncology is being described. It is demonstrated that it is possible to get
      detailed and current data by this method. It provides transparent data on
      equipment, personnel and workload in radio-oncology. It should set an example for
      other regions to collect their data in the same fashion, and then compile all
      such data for the whole country to identify and correct potential deficiencies
      for improvement of care.

PMID- 8992636
TI  - [Combined intraoperative and external irradiation of the celiac artery in the
      rabbit: the effects on the blood flow of the gastric mucosa].
AB  - AIM: To demonstrate changes in gastric mucosal blood flow caused by
      intraoperative radiotherapy of the celiac artery combined with external
      radiotherapy of the upper abdomen in a rabbit model. The study was designed to
      identify a possible correlation between a radiation-induced reduction in mucosal
      blood flow and the induction of gastric ulcer. MATERIAL AND METHOD:
      Intraoperative radiation doses of 0 or 30 Gy were given to the celiac artery in
      rabbits. After a delay of 14 days external radiotherapy of the upper abdomen with
      3 x 4 Gy/week to a maximum total dose of 40 Gy was initiated. Gastric mucosal
      blood flow was assessed by intraventricular injection of radioactively-labelled
      microspheres (15 microns) followed by measurement of radioactivity in the mucosa.
      The injections were performed at various time intervals between 2 and 63 days
      after intraoperative radiation. RESULTS: Intraoperative radiotherapy, including
      sham-intraoperative radiation, resulted in a transitory reduction of mucosal
      blood flow by about 50% of the control value on day 7 (Figure 3). After a
      temporary recovery by day 14, a marked and permanent reduction in blood flow was
      assessed after week 6. This time corresponds to the time of development of
      gastric ulcer. CONCLUSIONS: A relationship between the time of ulcer development
      and of reduced gastric mucosal blood flow was observed after combined
      intraoperative and external radiotherapy. The mechanical component of
      intraoperative treatment has to be emphasized. Reduced blood flow was also seen
      after intraoperative radiotherapy alone, without an induction of ulcer by this
      treatment. Hence additional mucosal damage by external radiation must be present
      for the induction of gastric ulcer.

PMID- 8992637
TI  - [The efficacy of radiotherapy in vertebral hemangiomas].
AB  - AIM: Assessment of the efficacy of radiation therapy for symptomatic vertebral
      hemangiomas. PATIENTS AND METHODS: Records of 19 patients who were treated from
      1969 to 1988 were retrospectively analyzed. Radiation treatment was given at 2 Gy
      per fraction to 20 Gy (n = 2), 30 Gy (n = 11), or 40 Gy (n = 6). Improvement of
      symptoms was chosen to determine the efficacy of the treatment. In addition the
      lesions were controlled radiographically. RESULTS: Symptomatic improvement was
      achieved in 17 of 19 patients, remission was complete in 7 patients. No dose
      response relationship was observed. The median time to improvement of symptoms
      was 3 months. The radiographic controls did not correlate with the clinical
      course. CONCLUSIONS: Radiation therapy is an effective treatment for symptomatic
      vertebral hemangiomas. The aim of the treatment is to ameliorate clinical
      symptoms, radiographic improvement is of minor importance.

PMID- 8992639
TI  - [Cancer in the children of survivors of acute leukemia or non-Hodgkin's lymphomas
      in childhood].

PMID- 8992638
TI  - [Acute tolerance in hyperfractionated accelerated whole-body irradiation].
AB  - BACKGROUND: Acute side effects of total body irradiation lead to intense
      molestations of the patients. Therefore, it is desirable to take measures to
      reduce these side effects. In a retrospective study the frequency of acute side
      effects of a hyperfractionated accelerated total body irradiation was assessed
      and compared to frequencies of other exposure schedules published in the
      literature. Additionally the influence of ondansetron on the frequency of nausea
      and vomiting was investigated. PATIENTS AND METHOD: From 1989 to 1992, 76
      patients (47 male, 29 female; median age 38 years) underwent total body
      irradiation before autologous bone marrow transplantation. They received 3 daily
      doses of 1.20 Gy each every 4 h on 4 successive days to a total dose of 14.40 Gy.
      Thirty-nine patients received 3 x 8 mg (daily, intravenous or per os) ondansetron
      during the whole course of irradiation. RESULTS: The most relevant side effects
      were nausea and vomiting. Patients, who did not receive ondansetron (n = 37)
      showed a nausea and emesis rate of 73%. With ondansetron (n = 39) nausea and
      emesis were reduced to 38%. Also the grade of severity of these side effects was
      reduced. CONCLUSIONS: Ondansetron proved to be an effective medicament for
      relieving nausea and vomiting during total body irradiation. The results obtained
      are in concordance with those published in the literature.

PMID- 8992640
TI  - [Is radiotherapy curative for stage-I and -II low-grade follicular lymphomas? The
      results a long-term follow-up study of patients treated at Stanford University].

PMID- 8992641
TI  - [Downstaging of esophageal carcinoma after preoperative radio- and chemotherapy].

PMID- 8992642
TI  - [The time of intramammary recurrence after breast-preserving therapy is decisive
      for patient prognosis].

PMID- 8992643
TI  - Marketing human organs: the autonomy paradox.
AB  - The severe shortage of organs for transplantation and the continual reluctance of
      the public to voluntarily donate has prompted consideration of alternative
      strategies for organ procurement. This paper explores the development of market
      approaches for procuring human organs for transplantation and considers the
      social and moral implications of organ donation as both a "gift of life" and a
      "commodity exchange." The problematic and paradoxical articulation of individual
      autonomy in relation to property rights and marketing human body parts is
      addressed. We argue that beliefs about proprietorship over human body parts and
      the capacity to provide consent for organ donation are culturally constructed. We
      contend that the political and economic framework of biomedicine, in western and
      non-western nations, influences access to transplantation technology and shapes
      the form and development of specific market approaches. Finally, we suggest that
      marketing approaches for organ procurement are and will be negotiated within
      cultural parameters constrained by several factors: beliefs about the physical
      body and personhood, religious traditions, economic conditions, and the
      availability of technological resources.

PMID- 8992644
TI  - Anencephalics as organ sources.
AB  - In recent years, the need for infant organs for transplantation has increased.
      There is a growing recognition of the potential use of anencephalics as sources
      of organs. Prevalent arguments defending the use of live anencephalics for organ
      sources are identified and criticized. I argue that attempts to deny the
      applicability of the "dead-donor rule" are either question-begging or based on
      false premises and that attempts to skirt the Kantian dictum against treating
      others as a means only are not successful. I contend that the apparent
      utilitarian justification for live anencephalics as organ sources is
      unsatisfactory for two reasons: first, because it ignores the undermining effect
      the policy would have on parental values and sentiments central to social
      welfare; and second, because attempts to respond adequately to the slippery slope
      argument against live anencephalic use are unconvincing.

PMID- 8992646
TI  - Transforming objectivity to promote equity in transplant candidate selection.
AB  - It is necessary to recognize the variety of levels at which values and norms may
      inappropriately affect the equity of the transplantation process, including
      candidate selection. Using a revised, richer concept of objectivity, adopted from
      Longino's work in the philosophy of science and empirical studies of candidate
      selection, this paper examines what sort of objectivity can be obtained in the
      transplant candidate selection process, and the closely related question of how
      selection can occur in an equitable manner. This concept of objectivity requires
      that transformative criticism occur so that (1) the conceptual and normative
      commitments underlying selection may be articulated and perhaps challenged, and
      (2) the relationship between those commitments and criteria for candidate
      selection may be examined and justified, or revised. Through such transformative
      criticism, a greater degree of objectivity may be attained, which in turn will
      increase the likelihood of equity.

PMID- 8992647
TI  - Of community, organs and obligations: routine salvage with a twist.
AB  - This paper makes the assumption that organ transplantation is, under some
      conditions at least, a proper use of communal medical resources. Proceeding from
      this assumption, the author: (1) sketches the history of the problem; (2) briefly
      examines the prevalent models of communal structure and offers an alternate
      version; (3) discusses notions of justice and obligation derived from these
      different models; (4) applies these to the practice of harvesting organs for
      transplantation; and then (5) offers a different process for harvesting organs
      from the newly dead. If community is viewed as united by a set of shred goals and
      common values among which the value of community itself is important, then
      certain reciprocal obligations among members obtain. I suggest that routine
      salvage of organs from the newly dead be instituted but that it be routine
      salvage "with a twist": rather early in life all members of the community are
      given the opportunity to refuse but their refusal carries the reciprocal
      condition that they cannot later become the recipients of that which they refuse
      to others.

PMID- 8992645
TI  - Should a criminal receive a heart transplant? Medical justice vs. societal
      justice.
AB  - Should the nation provide expensive care and scarce organs to convicted felons?
      We distinguish between two fields of justice: Medical Justice and Societal
      Justice. Although there is general acceptance within the medical profession that
      physicians may distribute limited treatments based solely on potential medical
      benefits without regard to nonmedical factors, that does not mean that society
      cannot impose limits based on societal factors. If a society considers the
      convicted felon to be a full member, then that person would be entitled to at
      least a "decent minimum" level of care--which might include access to scarce life
      saving organs. However, if criminals forfeit their entitlement to the same level
      of medical care afforded to all members of society, they still would be entitled
      to a kind of "rudimentary decent minimum" granted to all persons on simple
      humanitarian grounds. Almost certainly this entitlement would not include access
      to organ transplants.

PMID- 8992648
TI  - Normative and prescriptive criteria: the efficacy of organ transplantation
      allocation protocols.
AB  - Normative criteria adopted to assure just, equitable, and efficient allocation of
      donor organs to potential recipients has been widely praised as a model for the
      allocation of scarce medical resources. Because the organ transplantation program
      relies upon voluntary participation by potential donors, all such programs
      necessarily rely upon public confidence in allocation decision making protocols.
      Several well publicized cases have raised questions in North America about the
      efficacy of allocation procedures. An analysis of those cases, and the relevant
      technical literature, suggest consistent structural deficits exist in the organ
      allocation process as it is applied by many individual transplantation centres.
      These irregularities are based upon both the failure of rank waiting as a method
      to guarantee just treatment and a general failure to recognize the extent to
      which prescriptive criteria--social values--are commonly used to screen potential
      organ transplant candidates. Resulting idiosyncratic determinations, and a
      devaluation of rank waiting as a criterion, raise fundamental questions regarding
      justice, fairness, and equability in the application procedure at large. To
      correct these structural problems in organ allocation procedures, a
      multicriterion model defining prescriptive criteria through the Analytic
      Hierarchy Process (AHP) is proposed.

PMID- 8992649
TI  - [Utilization of serum banks for veterinary seroepidemiological research serving
      the Dutch livestock industry].
AB  - Various new developments confront livestock production, in which certification,
      monitoring and surveillance of animal health are becoming major items. In that
      respect serum banks can be a helpful epidemiological tool to provide valid data
      for decisions on prevention and eradication of disease. History, aims and use of
      serum banks and storage and freezing conditions are discussed. A plea is made to
      create serum banks for different animal species in the Netherlands.

PMID- 8992650
TI  - [A fault confessed is half redressed].

PMID- 8992651
TI  - [Postscript 'endocarditis in foals].

PMID- 8992652
TI  - [The practice needs a generally competent veterinarian].

PMID- 8992653
TI  - [KNMvD against increasing fixed numbers (Royal Dutch Society for veterinarians)].

PMID- 8992654
TI  - [Cyclosporine-induced hypertrophic gingivitis].

PMID- 8992655
TI  - [Neurohormonal regulation in generalized periodontitis in women].
AB  - The status of the principal hormonal systems has been examined in women with
      generalized periodontitis. Thyroid, adrenohypophyseal, sympathoadrenal, and
      gonadal hormones were studied. Statistical processing of the results revealed
      excessive shifts in all hormonal systems and at the inter-system level. A concept
      explaining the causes of the detected disorders is proposed.

PMID- 8992657
TI  - [The use of the preparation Tantum Verde in treating diseases of the oral
      mucosa].
AB  - The results of a clinical observation of 30 patients with oral mucosa disease are
      presented in the article. All patients got "Tantum Verde" as a local treatment in
      the dose of 15.0 ml 4 times a day for 6 days. The efficiency of the medicine as a
      mean of symptomatic therapy of acute and chronic oral mucosa diseases is proved
      as well as prospects for its use both separately and for complex therapy of these
      diseases.

PMID- 8992656
TI  - [The antifungal and immunomodulating lymphotropic therapy of candidiasis of the
      oral mucosa].
AB  - Lymphotropic and endolymphatic therapy was carried out in 52 patients with
      candidiasis of the buccal mucosa. After preliminary injection of lidase, levorin
      was injected subcutaneously in the middle third of the shin to patients in a
      standing posture, after which a cuff with 45-50 mm Hg pressure was placed on the
      femur for 2-2.5 hours. Immunocorrector thymogen was injected in the submaxillary
      and chin lymph nodes. A course consisted of 5-6 sessions. The status of the
      buccal mucosa normalized after treatment. Contamination of the mucosa with yeast
      cells appreciably decreased, the content of substances with medium-molecular mass
      in the saliva reduced, and cellular and humoral immunity parameters normalized.

PMID- 8992658
TI  - [The endogenous intoxication syndrome and the procedure for detoxication therapy
      in the treatment of suppurative diseases of the face and neck].
AB  - A total of 470 patients with inflammatory diseases of the maxillofacial area and
      neck were examined and treated. Acute inflammatory process was complicated with
      sepsis in 87 of them. Clinical and laboratory studies revealed that the intensity
      of endogenous intoxication depended on the phase of inflammatory process. This
      helped accurately differentiate between the intoxication degrees and develop
      detoxication strategy for each of them. Such a differentiated approach helped
      appreciably decrease the mortality in the group of patients with odontogenic and
      stomatogenic sepsis.

PMID- 8992659
TI  - [Indications for the use of tactivin in the combined treatment of phlegmons of
      the maxillofacial area].
AB  - The effects of subcutaneous and endolymphatic tactivin (in doses of 1 ml of 0.01%
      solution daily for 7 days) on clinical and immunological parameters were studied
      in patients with acute inflammations in the maxillofacial area, running a normo-,
      hypo-, and hyperergic course. Tactivin accelerated the arrest of inflammatory
      process and improved the patients' status, particularly so in cases with the hypo
      and hyperergic inflammations. The key role in the mechanism of the drug action
      is played by increase of the immunoregulatory index, which reflects the
      increasing resistance of the body.

PMID- 8992660
TI  - [A method for the surgical treatment of mandibular condyle fractures with
      dislocation of the head of the mandible].
AB  - A new method for surgical treatment of fractures of the condylar processes of the
      mandible with dislocation of the joint head is proposed. It consists in vertical
      osteotomy of the jaw branch, removal of fragments of the branch and joint head
      from the wound, intraosseous securing of fragments with a needle outside the
      operative wound, and fixation of the replant to the branch with 1 or 2 wire
      sutures. Sixteen patients were operated using this method, the outcomes were
      favorable.

PMID- 8992661
TI  - [The effect of ecological factors on the immunological indices of the oral cavity
      in children].
AB  - Effects of ecological factors on the immunological parameters of the oral cavity
      The immunological status of the oral cavity was assessed in children aged 9 to 12
      years living in different (cotton-growing and industrial) regions of Uzbekistan
      with different degrees of environment pollution. A reliable reduction of the
      parameters examined was observed in ecologically unfavorable regions. Health
      measures are proposed.

PMID- 8992662
TI  - [The functional and esthetic aspects in the orthodontic treatment of partial
      anodontia (anodontia 2/2)].
AB  - Rehabilitation of a female patient with adentia of the upper lateral incisors is
      described. An alternative method has been resorted to, including plasty of the
      upper lip frenulum followed by orthodontic treatment. The authors emphasize that
      the choice of such treatment strategy for this patient requires profound
      diagnostic studies in order to correctly design the prosthesis and plan the
      treatment scheme. Clinical assessment of individual occlusion is of primary
      importance, particularly in the lateral areas of dentition.

PMID- 8992663
TI  - [Dental restoration and the current filling materials].

PMID- 8992664
TI  - [The use of Foll's method of reflex diagnosis in orthodontics].
AB  - Twenty-five healthy subjects aged 9 to 20 were examined at different stages of
      treatment with permanent edgewise [correction of ejuice] orthodontic devices made
      in Russia. Foll's method of reflex diagnosis was used, which enables assessing
      the energy balance of individual organs and systems. The findings indicate that
      in 96% of examinees the use of the edgewise [correction of ejuice] technique led
      to functional depression, which manifested by allergies and disorders of blood
      and lymph circulation and endocrine system, the degree of depression depending on
      the compensatory potential of the body.

PMID- 8992665
TI  - [The characteristics of the design and use of metal-ceramic dentures in
      pathological abrasion of the hard dental tissues].
AB  - A total of 416 patients aged 40 to 60 suffering from abnormal teeth abrasion were
      fitted with cermet dentures. Orthodontic treatment was preceded by therapeutic
      and surgical preparation of the teeth and periodontium and by functional and
      adaptation rearrangement of the maxillodental system, if indicated. Remote
      results were assessed after 2 to 12 years. Due to such preparation good results
      were attained in 95.9% patients. Complications were observed in only 4.1%:
      exacerbation of periodontitis, ceramic facing chipping off, insertion of abutment
      teeth, and functional overload of the periodontium.

PMID- 8992666
TI  - [The practical problems in the orthodontic treatment of middle-aged and elderly
      patients with mental diseases].
AB  - Problems of orthodontic treatment of disabled subjects and elderly and senile
      patients suffering from mental diseases are discussed. Tendencies in the
      demographic processes in the world, increase in the number of such patients
      seeking outpatient stomatological advice, and experience gained by the author in
      many years permitted him to define the basic approaches to solution of these
      problems.

PMID- 8992667
TI  - [The importance of microbiological control over oral hygiene agents in the
      certification system].
AB  - The authors validate the necessity of microbiological control when certifying
      oral hygiene means. Results of microbiological expert evaluations of tooth
      pastes, gels, rinsing solutions, and other means are analyzed.

PMID- 8992668
TI  - [The level of secretory immunoglobulin A in the saliva and the body resistance of
      medical workers in the dental field].
AB  - Examinations of a group of dentists revealed that work at dentistry rooms
      involving a close contact of personnel with numerous allergens is conducive to
      decreasing the level of secretory IgA in the saliva. This indicates deterioration
      of the immune defense system of the body, particularly grave in nurses,
      orthodontists, and dental technologists.

PMID- 8992669
TI  - [The preparation of a hollow prosthesis for the filling of a defect in the
      maxilla after its resection].
AB  - A method for making a hollow postresection prosthesis is offered. Unlike the
      known methods, a cavity is formed in a ready prosthesis with a cutter from the
      side of the tongue. The cavity is closed with a plate (lid) by means of self
      hardening plastic. The weight of the prosthesis is appreciably reduced.

PMID- 8992670
TI  - [A computer-aided system for the management of a dental polyclinic].

PMID- 8992671
TI  - [The action of masticatory loading on the teeth].

PMID- 8992672
TI  - [The determination of the coagulation threshold of the electrolyte potassium
      chloride in human mixed saliva].

PMID- 8992673
TI  - [Purine analogs in chronic lymphatic leukemia].

PMID- 8992674
TI  - [Salt--an analysis of the connection between intake and health].
AB  - The average salt intake (sodium chloride) in Denmark is about 10 g/person/day,
      which is approximately 8 times higher than the estimated need. Salt added during
      industrial processing of foods constitutes more than 50% of the daily salt
      intake. Observational and experimental epidemiological studies indicate no
      decisive effects on blood pressure in humans caused by considerable variations in
      the daily salt intake. However, a small group of patients with hypertension may
      lower their blood pressure by reducing the daily intake of salt to 5 g. It has
      not been convincingly documented that high salt intake is an independent risk
      factor in the pathogenesis of asthma, osteoporosis, toxaemia of pregnancy or
      apoplectic stroke. On the other hand, several epidemiological studies point to
      the fact that the intake of salted foods may increase the risk of gastric cancer.
      It is recommended 1) that the food industry as far as possible limits the
      addition of salt, 2) that foods are supplied with a declaration of the salt
      content, and 3) that the research in this field is strengthened to facilitate the
      identification of persons at increased risk of developing disorders associated
      with high salt intake.

PMID- 8992675
TI  - [Vaccination of premature infants].
AB  - The article gives a review of the literature concerning immunization of preterm
      infants. The initial response to diphtheria-tetanus-whole-cell-pertussis vaccine
      and inactivated polio vaccine may be impaired in preterms, but after two and
      three doses the responses to these vaccines is comparable to those of term
      infants of the same chronological age. Likewise, the response to oral polio
      vaccine is normal and independent of gestational age after two and three doses in
      preterm infants. After two doses, the response to Haemophilus influenzae type b
      conjugate vaccine is impaired in preterm infants with very low gestational age,
      but comparable to that of term infants in preterms with higher gestational ages.
      After three doses the response to this vaccine is normal and unaffected by
      gestational age in preterms. Recombinant hepatitis b vaccine induces a reduced
      response in preterm infants even after three doses, and they may therefore need
      an extra dose of this vaccine. Studies of diphtheria-tetanus-whole-cell-pertussis
      vaccine and Haemophilus influenzae type b conjugate vaccine in preterm infants do
      not suggest that adverse effects occur more often or are more severe than those
      seen in term infants. The literature provides no background for postponement of
      immunizations in preterm infants.

PMID- 8992676
TI  - [Extrauterine pregnancy: diagnosis and treatment].
AB  - The incidence of ectopic pregnancy in Denmark has doubled since the beginning of
      the 1980's. A total of 2400 cases per year are identified corresponding to an
      ectopic localization in one of 40 pregnancies. An early diagnosis of ectopic
      pregnancy depends on the use of vaginal ultrasound examination and serial
      determination of the concentration of serum-HCG. By this information the
      diagnosis of an ectopic pregnancy can usually be established without the use of
      laparoscopy. In approximately 20% of the women the ectopic pregnancy regresses
      without treatment. Laparoscopic salpingotomy compared to treatment by laparotomy
      reduces the hospital stay and the convalescence period. The fertility is
      preserved in 60-80% of the women, if the contralateral salpinx has not previously
      been damaged. The possibility of making the diagnosis of ectopic pregnancy
      without laparoscopy has resulted in an increased interest in medical treatment.
      Repeated administration of methotrexate leads to regression of the ectopic
      pregnancy in approximately 95% of the treated women, however, 20% have temporary
      unpleasant side-effects. After treatment with a single dose of methotrexate, the
      side effects are avoided. The effectiveness, however, seems severely reduced.
      There is a need for a continued development of non-invasive methods for the
      treatment of ectopic pregnancy.

PMID- 8992677
TI  - [Chronic lymphatic leukemia. Peroral cladribine as primary treatment].
AB  - Ten patients with newly diagnosed B-chronic lymphocytic leukaemia were treated
      with cladribin orally for five days every four weeks with a median of four
      series. This is the first reported clinical study where a purine analogue is
      administered orally. The tumour reducing effect was fast. Eight out of 10
      patients responded with a partial or clinical complete remission. Two of these
      were in molecular biological complete remission. With an observation time of 22
      months we have seen no serious side effects so far. A randomized study (including
      a long term follow up) between chlorambucil, fludarabin and cladribin is needed
      to clarify the future role of cladribin in B-CLL treatment.

PMID- 8992678
TI  - [The combination of oral lysine-acetylsalicylate and metoclopramide compared with
      oral sumatriptan in the treatment of migraine attacks. A randomized, double
      blind, placebo-controlled clinical trial].
AB  - A combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg
      metoclopramide (LAS + MTC) was compared with oral sumatriptan (100 mg) and
      placebo in 421 patients with migraine in a randomized, double-blind, clinical
      trial. LAS + MTC was as effective as sumatriptan with a decrease in headache from
      severe or moderate to mild or none in 57% and 53%, respectively, for the first
      migraine attack treated, the primary efficacy parameter. Both treatments were
      better than placebo (success rate 24%, p < 0.001). LAS + MTC was better tolerated
      than sumatriptan (adverse events in 18% and 28%, respectively, p < 0.05).

PMID- 8992679
TI  - [Psoriasis treatment at the Dead Sea].
AB  - During the years 1975 to 1993 a total of 192 patients from Copenhagen with
      psoriasis, were sent to the Dead Sea, Israel, for a four week treatment of sun
      exposure and bathing. Total or almost total remission was obtained in 73% and
      significant improvement in 20% of the 163 patients at the post-treatment hospital
      control. A patient questionnaire filled in by 233 patients at the treatment
      centres in 1989-1991 showed that 88% of the patients were very satisfied with
      their stay. The length of remission was one to three months for 55% of the
      patients. Climate therapy is a valuable alternative treatment with an efficacy
      comparable to topical treatments for psoriasis.

PMID- 8992680
TI  - [Endometrial resection. Peroperative complications and postoperative course].
AB  - The effectiveness of transcervical resection of the uterine endometrium was
      assessed in 106 consecutive women admitted for surgical treatment for menstrual
      disorders, suitable for treatment with endometrial resection. No hormonal
      pretreatment was given. Amenorrhoea occurred in about 25%; 80% were satisfied
      after the initial treatment and 86% were satisfied if the procedure was repeated
      after at least one year postoperatively. The results were the same in 34 (32%)
      who had fibroids or polyps in the uterine cavity. No serious operative or
      postoperative complications appeared. Seven patients (6.6%) required temporary
      tamponade to control bleeding. It is concluded that endometrial resection is an
      advance in the management of menstrual disorders. The satisfaction in the
      patients is high and the complication rate low.

PMID- 8992681
TI  - [Term delivery in breech presentation. A registry-based study].

PMID- 8992683
TI  - [Chronic expectoration and risk of death in chronic obstructive lung disease].
AB  - We wished to determine whether excess COPD-related mortality in subjects with
      chronic mucus hypersecretion (CMH) could be explained by proneness to pulmonary
      infection. METHODS: 14,223 subjects of both sexes were followed for 10-12 years.
      Deaths with COPD as underlying or contributory cause (n = 214) were included and
      if death occurred in hospital, hospital records were obtained when possible (n =
      101). From information regarding increased or purulent mucus, fever, leucocytosis
      and chest X-ray during hospital admission, death was classified as caused by
      pulmonary infection (n = 38), not caused by pulmonary infection (n = 51), or
      unclassifiable (n = 12). RESULTS: Of subjects reporting CMH, 54% died from
      pulmonary infection, whereas that was only the case for 28% of subjects without
      CMH (p < 0.01). Cox regression-analysis showed a strong inverse relationship
      between ventilatory function and COPD-related mortality. CMH was an independent
      predictor of death with pulmonary infection implicated (RR:3.5) but not of death
      without pulmonary infection (RR:0.9). CONCLUSION: COPD-patients with CMH are more
      likely to die from pulmonary infection than COPD-patients without CMH.

PMID- 8992682
TI  - [Local guidelines for delivery with breech presentation. A nation-wide
      questionnaire].
AB  - All 30 Danish obstetric departments have answered a questionnaire focusing on
      local guidelines for delivery of singleton foetuses in breech presentation at
      term. Two departments recommended caesarean section to all parturients and ten
      departments to all primiparae. The criteria for recommendation of vaginal
      delivery varied, one department used pelvimetry, one did not attempt external
      version, ten did not permit induction of labour. All departments except two
      always had a specialist in obstetrics present at the delivery, 24 (of 28
      departments) an anaesthetist and 20 a paediatrician. The complexity in criteria
      and organisation reported is not surprising considering different recommendations
      in the literature, which means that the guidelines are primarily based on
      traditions and personal experience.

PMID- 8992684
TI  - [Post-traumatic stress disorder following violent events at the workplace.
      Experiences with patients referred to a department of occupational medicine].
AB  - Traumatic events within the working environment are common in certain kinds of
      jobs. The aim of this study was to describe the size and character of the
      traumatic event and the circumstances connected to the event in ten consecutively
      admitted patients to a department of occupational medicine. Furthermore to
      describe predisposing mental factors, the symptoms following the event and the
      relation between these symptoms and the symptoms used in the diagnosis of PTSD.
      It was found that only one of ten patients met all criteria for having the
      diagnosis of PTSD. Nine of 10 met all the symptom criteria, but the majority did
      not fulfil the criteria of having experienced an exceptionally threatening or
      catastrophic event. Several of the patients were characterized as having an anti
      aggressive nature and being highly ambitious in their jobs. Symptoms seem to
      remain for a long time. It was concluded that PTSD may follow even smaller
      stressful events. Predisposing mental factors and factors connected to the event
      may be of importance regarding the extent and duration of symptoms. Psychological
      treatment was experienced as valuable.

PMID- 8992685
TI  - [Isolated congenital growth hormone deficiency. Severe hypoglycemia and neonatal
      giant cell hepatitis].
AB  - A case of congenital isolated growth hormone deficiency with neonatal giant cell
      hepatitis is described. Hypoplasia of the pituitary gland was detected by a MR
      scan. Values of IGF-I, IGF-II, and IGF-BP-3 were low. Birth length and weight
      were normal; hypoglycaemia, jaundice, and failure to thrive were the most
      pronounced symptoms and present from the first day. Substitution therapy with
      growth hormone induced a remission of all symptoms. Growth was normal at follow
      up at the age of two and a half years.

PMID- 8992686
TI  - [Family practitioners on call and emergency departments integrated].

PMID- 8992687
TI  - [Cochlear implants in children--clinical research shows the way].

PMID- 8992688
TI  - [Smoking cessation in general practice].

PMID- 8992690
TI  - [Male infertility and micro-insemination].

PMID- 8992689
TI  - [Microscopic hematuria, dipstick hematuria. Evaluation of medical technology].

PMID- 8992691
TI  - [Micro-insemination with intracytoplasmic sperm injection].
AB  - Intracytoplasmic sperm injection (ICSI) is now established in the treatment of
      infertility. Fertilization is achieved by microinjection of a single spermatozoon
      into the ooplasma. Oligoasthenoteratozoospermia is the main indication, but ICSI
      is also used in cases of failed fertilization after standard IVF, retrograde
      ejaculation and male immunological infertility. In obstructive azoospermia ICSI
      is performed after aspiration of epididymal or testicular spermatozoa. In some
      anejaculatoric men spermatozon can be obtained following penile vibration or
      electro-stimulation, but they often have poor motility and ICSI may be used for
      fertilization. ICSI may also be used after thawing of semen cryopreserved prior
      to treatment of a malignant disease. Since 1991 the ICSI technique has been
      improved, and today the pregnancy rates are at least as good as after standard
      IVF. So far, studies of the foetuses and children born after ICSI show that the
      number of malformations and abnormal karyotypes is within the range of the normal
      population.

PMID- 8992692
TI  - [Breech presentation, vaginal delivery or cesarean section?].
AB  - Since the late sixties, the question of wether a breech presentation should be
      delivered vaginally or by caesarean section has been discussed by obstetricians,
      with special reference to the aim of improving foetal outcome. This review of the
      literature surveys the ante- and intrapartum considerations and activities which
      should be carried out in cases of breech presentation. The factors influencing
      foetal and maternal morbidity and mortality are discussed, and external cephalic
      version is considered. Based on these considerations and a careful examination of
      the pregnant woman and her obstetric history, we suggest vaginal delivery in
      strictly selected breech presentations. Selection criteria are given.

PMID- 8992694
TI  - [Usefulness of urine dipsticks in the diagnosis of microscopic hematuria].
AB  - The aim of this study was to evaluate the sensitivity of urine dipstick for
      diagnosing microscopic haematuria. We prospectively reanalyzed 122 consecutive
      urine samples, that had been read positive for blood by dipstick testing in two
      hospital departments, with repeated dipstick testing and fractionated microscopy
      at the laboratory. Out of these 53/122 (43%) were negative at the new dipstick
      analysis and 67/122 (55%) were negative by urine microscopy. We further examined
      urine samples from 31 healthy employees at the laboratory. Urine was collected
      before and after accurate instruction in the procedure for midstream urine
      sample. A complete correlation between dipstick analysis and microscopy was
      found. Samples from 8/31 (25%) persons showed microscopic haematuria before
      instructions and 6/31 (19%) after. It is concluded that instruction in correct
      dipstick reading and urine sampling could reduce the number of patients with
      microscopic haematuria by approximately 50%.

PMID- 8992693
TI  - [Examination of patients with monosymptomatic dipstick hematuria. A questionnaire
      study in Danish departments of surgery].
AB  - Routine procedures for urological investigations, treatment and follow-up of
      patients with monosymptomatic dipstick haematuria were studied by a
      questionnaire. This consisted of 13 questions and was filled in by the chief
      urologist in 45 (80%) of all surgical departments in Denmark. Dipstick testing
      was used by 98% of all departments, but only in 31% of these were the personnel
      reading the tests especially trained in the procedure. Cystourethroscopy and
      excretory urography were used in respectively 98% and 93% of the departments,
      although many different evaluation schedules were employed. Thirty-eight
      departments confirmed the initial dipstick result, of these 21 (55%) omitted
      further investigations in case of a negative result. Persistent monosymptomatic
      haematuria resulted in repeated urological examination in 36 departments (80%).
      The paper discusses the use of dipstick testing versus urine microscopy and gives
      recommendations for the investigation and follow-up of patients with
      monosymptomatic dipstick haematuria.

PMID- 8992695
TI  - [Menarche in relation to infertility and adult height and weight].
AB  - In order to clarify relationships between menarcheal age and fertility and
      fecundity later in life, a questionnaire was mailed to 3743 women, aged 15-44
      years, selected at random in the county of Copenhagen; 78% responded.
      Associations were observed between early menarche and increased risk of pelvic
      inflammatory disease and spontaneous abortion. On the other hand, no association
      was found between age at menarche and irregular bleedings, amenorrhoea,
      fertility, or fecundity. Early menarche was associated with excess weight, late
      menarche with underweight. A positive correlation was found between menarcheal
      age and final body height. It is concluded that menarche was not associated with
      fertility or fecundity, whereas early menarche was associated with pelvic
      inflammatory disease and spontaneous abortion. Age at menarche showed
      associations with height and weight.

PMID- 8992696
TI  - [Oxygen during delivery and cerebral vasoconstriction in preterm infants].
AB  - To determine if the use of oxygen in the delivery room influences subsequent
      global cerebral blood flow (CBF), 70 infants of gestational age of less than 33
      completed weeks were randomly assigned to receive room air (group I) or 80%
      oxygen (group II) during the initial stabilisation at birth. In group I
      supplemental oxygen was administered on clinical indications, when required.
      After being admitted to the neonatal intensive care unit all infants were treated
      according to our normal practice. At a postnatal age of two hours CBF was
      measured by xenon clearance. Seventy four per cent of the infants in group I were
      successfully established without the need for supplemental oxygen. CBF was
      significantly higher in group I than in group II (CBF median (interquartile
      range): 15.9 (13.6-21.9) vs 12.2 (10.7-13.8) ml/100 g/minute). Differences in
      oxygen exposure seemed to be the only explanation for the differences in CBF. No
      differences in short term outcome were found between the groups.

PMID- 8992697
TI  - [Skin prick tests with allergens in general practice].
AB  - Eleven general practitioners performed skin prick tests for specific pollen
      allergy (birch, timothy and mugwort) in 109 patients. One to two weeks later all
      109 patients were skin prick tested again by one and the same very experienced
      nurse in a specialised allergy clinic. The results of the allergy-nurse were
      defined as "the real values". When the two sets of skin prick test were compared,
      272 (83%) of all 327 skin pricks were of same size and class compared with the
      positive histamine-references. Forty-eight skin pricks (14%) were marginally
      different. Three skin prick tests (1%) were falsely positive and four (1%) were
      falsely negative. The study shows that general practitioners can after a short
      time of education and training perform and classify skin prick testing with great
      performance and at the same level as specialised allergy clinics. Skin prick test
      is a good supplement to clinical examination in general practice in the diagnosis
      of specific allergy in rhinoconjunctivitis and asthma bronchiale and in making
      suitable referrals to specialised allergy clinics.

PMID- 8992698
TI  - [Diagnosis of allergy in family practice].
AB  - Eleven general practitioners performed skin prick tests on suspicion of pollen
      allergy in 109 patients. The results were compared with the results of one and
      the same experienced nurse from a specialised allergy clinic, who skin prick
      tested the patients one to two weeks later. The results of the allergy-nurse were
      defined as "the real values". In 99 of the 109 patients (91%) the general
      practitioner's diagnosis of either specific pollen allergy or no allergy agreed
      with that of the nurse. The remaining 10 diagnoses (9%) were "false" compared
      with "the real values". The study confirms previous scientifically proven
      connections between pollen allergy and age, sex and month of birth. The study
      shows that general practitioners can following brief instruction investigate
      pollen allergy and achieve diagnostic results on a par with specialised allergy
      clinics. Specific pollen allergy diagnosis is essential for good symptomatic
      medical treatment of rhinoconjunctivitis and asthma bronchiale, for suitable
      referral to specialised allergy clinics, and, when possible, for prevention of
      allergic symptoms, including cross-allergic food allergy.

PMID- 8992699
TI  - [Headache, fatigue and edema of the lower limbs during the third trimester of
      normal pregnancy].
AB  - A series of 180 pregnant women with normal pregnancies participated in the study.
      A questionnaire concerning the presence of headache, fatigue and oedema of the
      lower limbs was filled out daily from the 30th gestational week to delivery.
      After the study period 120 questionnaires, of whom eight were excluded, were
      available for analysis. The weekly prevalences of headache and fatigue during the
      observation-period were nearly constant with values of 20% and 50%, respectively.
      The weekly prevalence of oedema increased significantly from 20% in the 31st week
      to 60% in the 42nd gestational week. Thirty-five percent had not suffered from
      headache, 22% did not report fatigue, and 42% did not describe oedema at all
      during the third trimester. The prevalence of headache and fatigue correlated
      significantly to increasing parity whereas headache was significantly correlated
      to decreasing age. Headache, fatigue, and oedema are common symptoms in the third
      trimester of normal pregnancy, and as such their presence alone should not
      usually give cause for suspicion of disease.

PMID- 8992700
TI  - [Interposition of the extensor tendon in a subcapital metacarpal fracture].
AB  - A case of an irreducibled subcapital fracture of the fifth metacarpal bone caused
      by interposition of the extensor tendon to the fifth finger and the
      intertendineous connection between the fourth and the fifth extensor tendons is
      described. To reduce the fracture the surgeon had to remove interposed tissue.

PMID- 8992701
TI  - [Should one take the safe measures in the prevention of NSAID-induced ulcers...].

PMID- 8992703
TI  - [Infections in connection with epidural catheterization].

PMID- 8992702
TI  - ["Radiomedical advice service"].

PMID- 8992704
TI  - [Preperitoneal plastic repair of the anterior abdominal wall in inguinal
      hernias].

PMID- 8992705
TI  - [The treatment problems in atherosclerotic vascular occlusions].

PMID- 8992706
TI  - [The surgical treatment of diuretic-resistant ascites in liver cirrhosis].

PMID- 8992707
TI  - [The etiological characteristics of acute pancreatitis (the results of a study at
      a specialized clinic)].

PMID- 8992708
TI  - [Cholelithic intestinal obstruction].

PMID- 8992709
TI  - [The clinical aspects of multiple primary tumors in patients with breast cancer].
AB  - The author made an analysis of results obtained during 20 years of examination
      and treatment of 1024 patients with multiple primary tumours of the mammary
      gland. Two and more malignant tumours were diagnosed in 404 patients and in 620
      patients malignancies were in combination with benign tumours. The combinations
      were noted with cancer of the second mammary gland, genitals, colon, stomach,
      skin, lung which is in agreement with literature data.

PMID- 8992711
TI  - [The late result after transplantation of the major duodenal papilla].

PMID- 8992710
TI  - [The lung reventilation syndrome after a superior lobectomy for a giant ectopic
      thymoma with prolonged compression of the chest organs].

PMID- 8992712
TI  - [Operations on the inferior vena cava in a general surgical hospital].

PMID- 8992713
TI  - [The possibilities of surgical treatment in injuries to the major blood vessels
      today].
AB  - Under analysis were results of surgical treatment of 47 patients with injuries of
      the aorta, major arteries and veins. Higher lethality was noted in people with
      injuries of major veins, especially vena cava. Specific operative methods are
      described for various kinds of injuries of the vessels of the thoracic and
      abdominal cavities. Lethality was 25.5%.

PMID- 8992714
TI  - [Extensive traumatic ruptures of the membranous portion of the trachea and
      esophagus].

PMID- 8992715
TI  - [The dynamics of the antiseptic resistance of the causative agents of soft-tissue
      suppurative-inflammatory diseases in children].
AB  - Opening of purulent foci in children with pyo-inflammatory diseases (PID) of soft
      tissues often leads to detection of staphylococcus aureus in the monoculture and
      different associations of this microbe with gram-negative bacteria in amounts
      exceeding the "critical level" responsible for the development of PID. Repeated
      examinations revealed a 2 times decreased frequency of detection of
      staphylococcus monocultures and 1.5 time less diversity of the association of
      microorganisms. Most efficient antiseptics among the investigated ones in
      relation to bacteria isolated in the opened purulent foci were found to be
      iodopyron, pervomur, boric acid, resorcinum, dioxidine.

PMID- 8992716
TI  - [Chronic duodenal obstruction in children].
AB  - Chronic duodenal obstruction was observed in 18 children aged from 2 months to 14
      years. The disease was caused by different malformations of the intestine. In
      children younger than 7 years of age the main clinical manifestation of the
      disease was the syndrome of vomiting. Older children were admitted for
      examination for the chronic abdominal pain syndrome. Roentgen-contrast methods of
      examination of the stomach and duodenum were of decisive significance. All the
      children were operated upon. The operative method was chosen according to the
      intestinal malformation.

PMID- 8992717
TI  - [First experience with the surgical treatment of young infants with congenital
      pathology of the locomotor system].
AB  - The authors have revised traditional principles of treatment of children with a
      congenital pathology of the locomotor system. Early treatment has been shown to
      be necessary beginning from infancy since the operations have a more favourable
      course. Normal anatomo-physiological correlations of the locomotor system are
      being formed from the early days and months of the infants. Good immediate
      results were obtained in 22 children. The authors recommend to establish terms of
      the operative interventions for orthopedic abnormalities immediately after birth
      in the maternity home.

PMID- 8992718
TI  - [The results of operations for open reduction with capsular hip joint
      arthroplasty in congenital hip dislocation in children].
AB  - The authors make an analysis of results of operations for open setting with
      capsular arthroplasty of the hip joint, derotational supratrochanteric
      denticulate osteotomy and resection of the femur with creation of iliofemoral,
      ischiofemoral and pubofemoral ligaments from the residual proximal part of the
      capsule in 56 children with congenital dislocation of the femur. Long-term
      results were studied in 46 children, 35 of them having good results and 8 having
      satisfactory results.

PMID- 8992719
TI  - [The classification and surgical correction of postlactation involution of the
      breasts].
AB  - On the basis of investigations performed a classification is made systematizing
      postlactational involution according to different parameters and degree. It
      facilitates objectivization of indications to different correcting operative
      interventions on mammary glands with postlactational involution and choice of the
      optimum complex of surgical measures for correction of the mammary gland. It
      allows prognosis of its contour and esthetic results.

PMID- 8992720
TI  - [The conservative treatment of trophic ulcers of the lower extremities with the
      impossibility of a surgical intervention].
AB  - Dressing with a paste of an original composition is recommended for ambulatory
      treatment in combination with a prolonged local novocaine blockade. The
      recommendation is based upon the author's experience with treatment of 52
      patients.

PMID- 8992721
TI  - [The bioelectrical activity and evacuatory function of the digestive tract
      studied in the diagnosis of acute surgical diseases of the abdominal cavity
      organs and of postoperative complications].
AB  - Functions of the digestive tract were studied in 46 patients by an original
      method worked out by the authors. Its diagnostic and prognostic significance is
      shown.

PMID- 8992722
TI  - [A trial of the clinical use of thienam in treating severe and life-threatening
      suppurative-septic complications].
AB  - The authors share their experiences with treatment of 12 patients using the
      antibiotic Tienam. No complications resulting from the administration of this
      medicine were noted. High therapeutic efficiency of Tienam has been shown.
      Recovery was noted in 11 out of 12 patients.

PMID- 8992723
TI  - [The causes of incompetence of the duodenal stump and gastroenteric anastomosis
      and the means for its prevention in the surgery of duodenal ulcers].
AB  - Causes of the incompetence of stump sutures in resection of the stomach observed
      in 90 out of 3479 patients with chronic duodenal ulcers were analyzed. Most
      patients were found to have a combination of general and local factors. Among the
      local factors the leading one was appearance of a large inflammatory infiltration
      around the "active" ulcers. The endoscopic autohemoapplication to the ulcer
      included in the complex of preoperative preparation of the patients reduced the
      frequency of incompetence of sutures from 2.58% to 1.33%.

PMID- 8992724
TI  - [The causes and prevention of neurological disorders in the surgical treatment of
      varicose disease].
AB  - Frequency of the appearance of neurological disturbances was studied after
      operative treatment of varicose disease in 422 patients. The topographo
      anatomical correlations of subcutaneous nerves and lower extremity veins were
      also investigated in 40 corpses. The authors' original method was used in
      operations on 82 patients. Neurological disturbances-such as disturbances of skin
      sensitivity-were noted in 38.6% of the investigated people. Their cause is
      thought to be the mutual sheath between the subcutaneous vein and nerves in the
      shin. The endovasal autovenous occlusion of the main trunks of the subcutaneous
      shin vein with the help of the autovein taken from the thigh was made to avoid
      traumatism.

PMID- 8992725
TI  - [Postoperative recurrences of varicose dilation of the subcutaneous veins of
      lower extremities].
AB  - Causes of recurrent varicosities of the subcutaneous vein (VSV) of lower
      extremities were studied in 331 patients operated upon. It was established that
      the main cause of recurrent VSV was tactical and technical errors. The use of the
      hollow vein stripper for the intraoperative detection of insufficiency of the
      communicating veins was shown to be justified.

PMID- 8992726
TI  - [The correction of the fatty acid composition of erythrocyte membrane
      phospholipids by infusions of a fat emulsion].

PMID- 8992727
TI  - [Ways to improve the transfusion support of surgical hospitals under current
      conditions].
AB  - The article touches upon problems of the improvement of transfusiological
      maintenance of surgical departments with new tendencies in the donor movement
      taken into account. Specific methods to gain this aim are proposed.

PMID- 8992728
TI  - [A method for local dermatoplasty in cicatricial contractures of the neck].

PMID- 8992729
TI  - [A method for restoration of the knee joint ligaments].

PMID- 8992730
TI  - [The diagnostic potentials of thermal imaging in clinical practice].

PMID- 8992731
TI  - [The use of therapeutic fasting for the preoperative preparation of obesity
      patients].

PMID- 8992732
TI  - [Fiber gastroscopy as the first stage in screening for diseases of the upper
      gastrointestinal tract].
AB  - The article presents data of 284 out of 3400 endoscopic investigations as a
      method of primary examination in screening of pathology of the upper parts of the
      gastro-intestinal tract. They show advantages of screening gastroscopy over
      multistage screening investigations and generally accepted clinico-instrumental
      tests in forming the groups of risk in oncology and surgical gastroenterology.

PMID- 8992734
TI  - [Khristian Khristianovich Salomon (1796-1851)].

PMID- 8992733
TI  - [The surgery of peptic ulcer in middle-aged and elderly patients].

PMID- 8992735
TI  - [Professor I. S. Babchin and Russian neurosurgery].

PMID- 8992736
TI  - [The role of Soviet surgeons in the formation and development of surgical
      stomatology in Russia].

PMID- 8992737
TI  - [Revision endoprosthesis (the complications of primary endoprosthesis)].

PMID- 8992738
TI  - [Malignant stomach tumors in patients who have had a vagotomy for duodenal
      ulcers].

PMID- 8992740
TI  - [Methodological approaches to the planning of hospital medical care in military
      treatment and prevention institutions].

PMID- 8992739
TI  - [New requirements for civilian health status in the Regulation on Military
      Medical Expertise].

PMID- 8992741
TI  - [The characteristics of penetrating gunshot wounds of the chest received during
      combat operations].

PMID- 8992742
TI  - [The diagnosis and treatment of coagulated hemothorax after gunshot trauma to the
      chest].

PMID- 8992743
TI  - [The results of correcting venous insufficiency and disorders of the peripheral
      lymph circulation in postthrombotic disease].
AB  - Isolated correction of venous component of chronic lymph-venous insufficiency by
      a way of dressing of perforated veins, extravasated correction of valves of deep
      veins and femoral cross shunting (24 patients of control group), and also
      combined correction, supposing the same operations in combination with creation
      lymph-venous anastomosis (22 patients of main groups) at infringement of
      peripheric flow of lymph and venous insufficiency in patients with edematous form
      of posttraumatic diseases have been carried. The complex estimation of efficiency
      of operative treatment on subjective and objective attributes of illness is
      offered. Direct and remote postoperative results proved to be more preferable in
      main group.

PMID- 8992744
TI  - [The dynamics of anti-influenza immunity in sailors of the Baltic Fleet].

PMID- 8992745
TI  - [The microflora of gunshot and explosive mine wounds in victims delayed for a
      long time at the prehospital stage].
AB  - The clinico-microbiological research of gunshot and mine-explosive injuries in
      wounded servicemen of Afghanistan army, arriving on stage of the qualified
      surgical care for 2-5 days after wound is lead. The quantitative and qualitative
      structure of wound microflora at modern combat trauma on a prehospital stage is
      determined. It was established, that main kinds of wound infectious complications
      in injuries are suppuration of wounds and clostridial infection. The advantages
      and the lacks of benzyl penicillin for prophylaxis of wound infection are
      investigated.

PMID- 8992746
TI  - [Functional changes in the cardiovascular system in exposure to ionizing
      radiation against a background of stress and concomitant diseases].

PMID- 8992747
TI  - [Three centuries of the medical service of the Naval Fleet].

PMID- 8992748
TI  - [The syndrome of post-cruise disorders].

PMID- 8992749
TI  - [The possibility of the occurrence of hyperventilation apnea and loss of
      consciousness].
AB  - In work influence of various temporary modes of free hyperventilation of the
      lungs was investigated, usually used by the sportsmen before diving on reduction
      of the contents of CO2 in exhaling air of healthy men-divers. Attention was paid
      to the opportunity of occurrence of posthyperventilation apnea and loss of
      consciousness. It is shown, that washing away CO2 from organism at
      hyperventilation is limited. Hyperventilation (their depth and frequency was
      chosen arbitrary), spent during 60, 120, 180, 360 seconds causes in healthy
      trained men apnea and loss of consciousness.

PMID- 8992750
TI  - [A method for evaluating the safety of decompression regimens for divers].
AB  - The authors offer a way of estimation of safety modes of decompression, based on
      definition of intensity of venous gas embolism (VGE) at each decompression and
      account of probability of illness of divers in series of tests. Intensity of VGE
      was determined with the help of ultrasonic gas bubbles Doppler radar. Comparative
      safety of standard modes of decompression of divers of the Navy was estimated,
      and also the modes, designed in accordance with mathematical model of
      decompression, offered by I. A. Voitsekhovich (1990), were done. The results
      testify, that use of ultrasonic radar for estimation of intensity of VGE at
      decompression and account of average and maximum probability of decompression
      illness in series of tests of modes permit to receive the comparative
      characteristic of safety of modes at small number of decompressions.

PMID- 8992751
TI  - [Experience in supplying the family members of servicemen with drugs in
      outpatient treatment].

PMID- 8992752
TI  - [Fitovit and other medicinal species in the treatment of dysbacteriosis].

PMID- 8992753
TI  - [The development of dental care in the Russian navy].

PMID- 8992754
TI  - [Military naval medicine in the collections of the Military Medical Museum].

PMID- 8992755
TI  - [The names of Russian physicians on the world map].

PMID- 8992756
TI  - [A. G. Bakherakht--the founder of Russian naval hygiene].

PMID- 8992757
TI  - [The 60th anniversary of the Hospital of the Northern Fleet].

PMID- 8992758
TI  - [The 70th anniversary of the Dushanbe Military Hospital].

PMID- 8992759
TI  - [The half-century anniversary of the first hospital of the Missile Forces].

PMID- 8992760
TI  - [Work experience of the pediatric polyclinic in a closed garrison of the Military
      Space Forces].

PMID- 8992761
TI  - [Medical support for the naval forces in armed conflicts and local wars].
AB  - The authors give the analysis of medical maintenance of local wars and military
      conflicts of the last decades. Peculiarities of the combat actions, system of
      treatment and evacuation measures, peculiarities of rendering of all kinds of the
      medical care are considered. Are formulated the regulations, necessary for
      inclusion of domestic hospital ships and units of marine corps in structure of
      forming mobile forces for action on seaside directions.

PMID- 8992762
TI  - [Nondrug methods for the rehabilitation of participants in the cleanup of the
      aftermath of accident at the Chernobyl Atomic Electric Power Station who have
      neurocirculatory dystonia and hypertension].
AB  - Among cardiovascular diseases registered in the Chernobyl wreckers
      neurocirculatory dystonia and hypertension occur most frequently. Combined
      treatment including electric sleep, iodinebromine baths, therapeutic exercise,
      massage relieves clinical symptoms, promotes positive rearrangement of
      hemodynamics, a decrease in myocardial hyperkinesis and vegetative dysfunction,
      an increase in cardiovascular reserves, correction of hypersympathicotonia and
      immune disorders.

PMID- 8992763
TI  - [Physical factors in the combined treatment of patients with postthrombophlebitic
      disease of the legs].
AB  - 95 patients with postthrombophlebitis affection of the lower limbs were treated
      according to three schemes: conventional therapy alone (anticoagulants, anti
      inflammatory therapy, etc.), training of collateral circulation plus minimal
      standard chemotherapy, training of collateral circulation plus local and
      endovasal laser radiation plus minimal standard chemotherapy. A total of 75
      patients were treated (27, 32 and 36 patients of group 1, 2 and 3, respectively).
      The best results were achieved in group 3.

PMID- 8992764
TI  - [The use of sodium chloride baths in patients with chronic bronchitis].
AB  - 80 patients with chronic bronchitis took baths with sodium chloride concentration
      20, 40, 60 g/l and temperature 37-38 degrees C. The baths produced a positive
      effect on central and regional hemodynamics, reduced inflammation and
      sensitization.

PMID- 8992765
TI  - [The effect of geophysical and meteorological factors on the course of chronic
      obstructive lung diseases at a low-mountain altitude].
AB  - In the climate of north Kirghizia meteoropathologic reactions arise in patients
      with chronic obstructive bronchitis in the time of cold atmospheric front
      passing, are spastic, phasic, associated with pulmonary circulation and growing
      generalized bronchial obstruction. Prefrontal period (weather hypoxia) is
      meteoropathogenic for asthmatics who are responsive to geophysical disturbances
      influencing obstruction of the small bronchi.

PMID- 8992766
TI  - [The effect of combined transcerebral magnetic and electric impulse therapy on
      the cerebral and central hemodynamic status of stroke patients in the early
      rehabilitation period].
AB  - 75 clinical cases of acute impairment of cerebral circulation treated with
      sinusoidal modulated currents in combination with transcerebral magnetic field
      have been analysed. Functional and clinical findings indicate that the above
      combination is much more effective than magnetic field and sinusoidal modulated
      currents alone: 62% against 35% and 33%, respectively.

PMID- 8992767
TI  - [The effect of balneotherapy on the autonomic indices in children with
      neurocirculatory dystonia].
AB  - Intervalocardiography was used to study the effect of carbon dioxide narzan baths
      on autonomic parameters in 125 children aged 10-15 with vascular dystonia (VD).
      In sympathicotonic VD vegetative background and reactivity did not change much.
      In vagotonic VD balneotherapy was adequate.

PMID- 8992768
TI  - [The laser therapy of median nerve neuritis in a biocontrol mode].
AB  - Treatment of neuritis of nervus medianus goes on much faster if biocontrolled
      regimen of laser therapy synchronization with blood rhythms of the patient is
      introduced. Estimation of the nervus conductivity recovery rate and muscular
      contractility was based on the data obtained at broadened electrodiagnosis with
      sinusoidal modulated currents.

PMID- 8992770
TI  - [The action of impulse currents of different frequencies on the recovery
      processes in the body of rats in the modelling of hyperlipoproteinemia].

PMID- 8992769
TI  - [The use of sinusoidal modulated currents and iodobromine baths in treating
      patients with the "stone pathway" of the upper urinary tract].
AB  - After exposure to sinusoidal modulated currents and iodinebromine baths there was
      a decrease in serum levels of calcium, alanin aminotransferase, lactate
      dehydrogenase and urinary calcium, oxalates, leukocytes, red cells, acceleration
      of radiopharmaceutical accumulation (Tmax) and elimination from the kidneys
      (T1/2), urolith fragments (1-5 mm in size) elimination from the upper urinary
      tract in 21 (48.9%) out of 43 patients. The above physiotherapeutic complex is
      indicated for urolithiasis patients with associated diseases (hyperesthesia,
      causalgia).

PMID- 8992771
TI  - [The use of interference currents in the therapy of patients with chronic
      prostatitis].

PMID- 8992772
TI  - [The effect of carbonate mineral water on the water-electrolyte metabolic status
      in experimental nephrocalcinosis].

PMID- 8992773
TI  - [The importance of electroencephalographic studies for evaluating the action of
      physical treatment methods in patients with a neuroendocrine syndrome and
      disordered menstrual function].
AB  - Electroencephalograms of 43 females (mean age 27.3 +/- 5.2 years) were examined
      for integral power of various EEG rhythms, delta, beta, alpha, beta 1 intervals
      for occipital, parietal and frontal region, right and left hemispheres. The
      frequency analysis was made with regard of EEG type. A particular role of the
      right hemisphere in development of neuroendocrine pathology is discussed.

PMID- 8992774
TI  - [Potable mineral waters as the correctors of the hormonal and motor-evacuatory
      disorders in chronic alcoholic intoxication].
AB  - Long-term history of alcohol drinking is associated with shifts in basal levels
      of glucagon, gastrin, cortisol and insulin. The longer history of alcohol abuse,
      the more pronounced the shifts were. Besides hormonal unbalance, the animals had
      defective gastrointestinal motility and evacuation. Drinking of mineral water can
      correct the above disturbances only in short-term alcoholic intoxication.

PMID- 8992776
TI  - [Hypoxic training at intervals in the treatment of hypothyroidism].

PMID- 8992775
TI  - [Changes in membrane permeability under the action of the naphthenic hydrocarbons
      in naphthalan].

PMID- 8992777
TI  - [The possible mechanism of the hypolipidemic action of low-energy laser radiation
      in patients with ischemic heart disease].

PMID- 8992778
TI  - [The clinical efficacy of hydrogen sulfide baths in ischemic heart disease in an
      arid zone].

PMID- 8992779
TI  - [The evaluation of the physical work capacity of participants in the cleanup of
      the aftermath of the accident at the Chernobyl Atomic Electric Power Station
      during their rehabilitation at a health resort].

PMID- 8992780
TI  - [Physiotherapy in injuries to the peripheral nerves of the extremities].

PMID- 8992781
TI  - [Physiotherapeutic prescribing in gynecological practice (a short guide)].

PMID- 8992782
TI  - [The 75th anniversary of the Tomsk Research Institute of Health Resort Medicine
      and Physiotherapy].

PMID- 8992783
TI  - [The effect of infrared laser radiation of different frequencies on the healing
      of skin wounds].
AB  - In experiments on white rat males it was established that infrared laser
      radiation (frequency 500 Hz) was more potent in stimulating repair of skin wounds
      than 3000 Hz radiation. This manifested in enhanced proliferative activity of
      fibroblasts and epithelial cells, decreased areas of the wound.

PMID- 8992784
TI  - [Risk to patients by virus-infected physicians?].

PMID- 8992785
TI  - ["Hypophyseal hormones" in the testis--"entropy" in endocrinology].

PMID- 8992786
TI  - [Telemedicine].
AB  - Telemedicine includes all medical activities in diagnosis, therapeutics or social
      medicine undertaken by means of an electronic transfer medium, thereby enabling
      the transmission of visual and acoustic information in these fields over long
      distances without the doctor being personally present at the requested
      consultation. Most experience in telemedicine has been gathered in diagnosis,
      especially with respect to teleradiology and telepathology; however, an
      increasing number of institutions have obtained experience in teledermatology,
      telepsychiatry, telecardiology, telesurgery, etc. The quality of the transmitted
      images is adequate for diagnostic application. However, the transfer rates of
      normal telephone lines are not satisfactory and these telephone nets will be
      replaced by ISDN and broad band or satellite connections in the near future. The
      lack of uniform transfer standards is the most important constraint in
      telepathology. This fact is one explanation for the fast growth of the Internet,
      which is based on unified transmission standards. The rapid expansion of
      telemedicine is inevitable and the increased use of this tool will induce
      profound changes in the medico-social environment. There is a fear of
      institutional concentration, at the expense of small institutions. This
      development can be minimised by augmenting the scope to encompass telemedicine in
      all interdisciplinary fields, with the consequent full integration of small
      institutions. Telemedicine is an appropriate technique for quality assurance in
      all areas of medicine, since it permits simultaneous "soft" quality control, in
      conjunction with assumption of co-responsibility by the control institution.

PMID- 8992787
TI  - [The testis as eutopic production site of human growth hormone, placental
      lactogen and prolactin: possible autocrine/paracrine effects on testicular
      function].
AB  - The human (h) protein hormones, growth hormone (hGH-N) and prolactin (hPRL), are
      mainly produced in the pituitary, whereas the human placenta expresses the other
      four members of the protein hormone gene family, designated placental lactogens
      (PL-A, PL-B, PL-L) and growth hormone variant (GH-V), GH-N stimulates somatic
      growth, supports nitrogen-, phosphate- and potassium retention and promotes
      lipolytic and anabolic metabolism, whereas PRL acts on the mammary gland and
      induces mammogenesis, lactogenesis and galactopoesis. Both hyperprolactinemia and
      growth hormone deficiency affect the onset of puberty and reproduction in man and
      mice. In addition to the glycoprotein hormones, these hormones play a role in the
      maintenance of testicular function. Our group previously demonstrated eutopic
      production of glycoprotein hormones hLH (human luteinizing hormone) and hCG
      (human chorionic gonadotropin) in the testis. We have now extended our
      investigations to the local testicular expression of protein hormones. By means
      of the molecular biology techniques of the reverse transcription-polymerase chain
      reaction (RT-PCR), Southern blot and by restriction endonuclease analyses of the
      generated PCR products we demonstrated the eutopic expression of genes coding for
      the protein hormones. GH-N gene transcripts were detected only in the pituitary
      and abundant PL-A/B and a few GH-V gene transcripts were demonstrable in the
      placenta. In contrast, in the testis GH/PL and PRL genes are transcribed. Since
      testicular protein hormone gene expression is rather low, these hormones may act
      locally and not as systemic factors; they presumably modulate the LH/CG-mediated
      testosterone biosynthesis and/or may act on the spermatogenesis.

PMID- 8992788
TI  - [Ostium stenosis of the left coronary artery after aortic valve replacement--2
      case reports].
AB  - The development of left main coronary artery stenosis is a rare complication
      arising after aortic valve replacement. We report the different clinical course
      of two cases. One patient developed typical exertional angina 3 months after
      uneventful aortica valve replacement. Coronary stenosis had been excluded on
      preoperative coronary angiography. One day before hospital admission for coronary
      angiography the patient died suddenly. The second patient reported symptoms
      typical of angina 6 months after aortic valve replacement. Coronary angiography
      revealed critical left coronary ostial stenosis, which was successfully treated
      by surgical revascularization. These cases demonstrate the rare, yet potentially
      fatal complication of left coronary ostial stenosis. Early coronary angiography
      seems warranted in the event of typical exertional angina, even after
      angiographic exclusion of relevant coronary artery stenosis before aortic valve
      replacement.

PMID- 8992789
TI  - [The legal status of telemedicine in Austria].
AB  - The rapid development of modern communication technologies offers new
      opportunities for medical diagnosis and treatment. In spite of the obvious
      theoretical benefits of telemedicine, which have been proven by many projects in
      practice, telemedicine has not become generally established in Europe. Besides
      lack of technical standardisation and high purchase costs, one of the reasons
      might be the as yet unclarified legal situation. Taking the present legal
      situation in Austria we tried to explore questions of liability concerning
      telemedicine. The outstanding point seems to lie in the contract between the
      participating physicians on the one hand and between the physicians and the
      patient on the other hand. If the consulting physician is self-employed he has to
      take responsibility for any error on the part of the consulted physician.
      However, if he is working in a hospital, then he is legally considered an
      "Erfullungsgehilfe" (person employed by the debtor in the performance of his
      obligation) an any further doctor consulted is automatically also an
      "Erfullungsgehilfe" of the hospital and therefore the hospital takes
      responsibility for any mistakes made by the consulted physician. Although there
      has not been any specific jurisdiction concerning telemedicine in Austria, the
      present legal provisions are adequate for reaching decisions on questions of
      liability, so that there are no objections from the legal point of view to the
      general implementation of telemedicine.

PMID- 8992790
TI  - Psychiatry struggles to find managed care fit.

PMID- 8992791
TI  - Advocates, HMOs evaluate psychiatric services under managed care.

PMID- 8992792
TI  - Patient finds communication is managed care advantage.

PMID- 8992793
TI  - I was a success at everything--except suicide.

PMID- 8992794
TI  - Psychiatric patient faces major personal costs.

PMID- 8992795
TI  - Managed, unmanaged or mismanaged care?

PMID- 8992796
TI  - Bob Cratchit on the couch.

PMID- 8992797
TI  - Lithium, a multi-edged sword: the past, present, and future.

PMID- 8992798
TI  - Incidence of dog bites in Milwaukee, wis.
AB  - Dogs are everywhere. The incidence of and injuries caused by dog bites have grown
      to such epidemic proportions in certain parts of the United States that they are
      now considered a major public health concern. Playful Rover is no longer a
      harmless pet. Uncontrolled, he now can be considered a public nuisance. In this
      study, we evaluated the epidemiology of dog bites recorded in Milwaukee, for
      calendar years 1989-1991. This assessment included anatomical location of bites,
      victims' ages, behavioral antecedents, leading up to the bite incidents, season
      of the year, and animal ownership. The evaluation also measured the correlation
      coefficient between the frequency of dog bite incidents and median household
      income distribution within the city. During the 3-year period, a total of 3,926
      animal bites, including 3,244 (83%) dog bites, were reported to the City of
      Milwaukee Department of Health. Of all the dog bites reported, 60% were on the
      upper extremities. Children less than 15 years old sustained 44% of the injuries,
      mostly to the head and face. Provocation by the victim accounted for 19% of the
      cases. The majority of the incidents (67%) occurred during the spring and summer
      months. In 49% of all cases, the victims families or neighbors owned the animals
      involved in the biting. Researchers also observed a significant negative
      correlation between bites and median household income distribution. Study results
      suggest a need to educate the public about the magnitude of dog-bite problems,
      enforce leash laws and impound stray dogs as an integral part of prevention
      programs.

PMID- 8992799
TI  - Animal bites and rabies: physicians and veterinarians must work together.

PMID- 8992800
TI  - Trends in breast cancer mortality for blacks and whites in Wisconsin and the
      United States, 1979-1992.

PMID- 8992801
TI  - Reviewing gag clauses in managed care contracts.

PMID- 8992802
TI  - CD-ROM technology: building a computer-based reference set.

PMID- 8992803
TI  - Post-retirement health coverage.

PMID- 8992804
TI  - [The value of ultrafast computerized tomography in detection of the patency of
      coronary bypasses].
AB  - Bypass graft patency with ultrafast computed tomography (= Electron Beam
      Tomography, EBT) was examined in 72 bypass grafts (47 saphenous veins, 25
      internal mammary arteries) in 30 patients and compared with coronary angiography.
      Angiography was performed a mean of 4.4 +/- 3.5 months (range 1-13) from the EBT
      examination. Contrast material (120 ml) was continuously administered via a
      peripheral vein and 40 axial slices (3 mm slice thickness, 110 ms scan time)
      without overlap sequences were obtained, ECG triggered with the single slice
      scanner mode. Imaging of internal mammary artery grafts began at the thoracic
      inlet, for saphenous vein grafts, at the undersurface of the aorta. Sixty of 63
      angiographically patent bypass grafts were determined patent by EBT (sensitivity
      95%), 8 bypass grafts could not be detected by EBT, and 9 were angiographically
      occluded (specificity 89%). Twenty-four of 25 internal mammary artery grafts were
      patent at EBT and coronary angiography, one was occluded. In 27 of the 30
      patients (90%), all of the angiographically patent grafts could be confirmed as
      open with EBT. Obstructions of 10 grafts could not be visualized with EBT. Graft
      insertion into native coronary vessels could be visualized in axial slices,
      although morphologic quantification of graft insertion stenosis (75-90%) in two
      cases was not possible. Three dimensional reconstruction of the 40 axial slices
      allowed graft anatomy to be delineated. Visualization of bypass insertion into
      the native coronary vessel was less successful because of opacification of the
      left and right ventricle. Electron beam computed tomography is a minimally
      invasive procedure capable of evaluating the patency of saphenous vein and
      internal mammary artery grafts. The morphologic quantification of graft
      obstruction and visualization of the insertion of the bypasses into the native
      coronary vessels is less successful with present technology and imaging
      modalities.

PMID- 8992805
TI  - [Incidence and management of acute left main coronary artery dissection as a
      complication of acute transluminal coronary angioplasty].
AB  - Out of 1730 consecutive patients undergoing percutaneous transluminal coronary
      angioplasty (PTCA) of left descending coronary artery (LAD) or circumflex artery
      (CX) five patients (0.3%) suffered an acute dissection of left main coronary
      artery. In three patients dissection developed because of manipulation of the
      guiding catheter. In one patient retrograde dissection of the left main stem
      occurred because of balloon angioplasty of ostial LAD stenosis and in a second
      patient because of balloon rupture in the setting of stent deployment in the
      proximal part of the LAD. Four patients were selected for emergency operation,
      but one patient died before reacting the operation theatre. Out of the three
      remaining patients one patient died postoperatively and another patient suffered
      a transmural myocardial infarction. In the fifth patient three AVE Micro stents
      were implanted; one just at the origin of the LAD, one at the origin of the CX
      and the third in the left main stem. This patient was not sent for operation and
      was discharged without symptoms.

PMID- 8992807
TI  - [Quality assurance in invasive and interventional cardiology in Austria in 1994.
      Commissioned by the Interventional Cardiology Working Group of the Austrian
      Cardiology Society].
AB  - A complete National Database is the prerequisite for quality control, quality
      management and improvement. In Austria, we have been reaching for this goal since
      more than three years. 21 094 diagnostic coronary angiographies (CA) and 4934
      PTCAs were performed in all 27 centers (out of which 17 perform PTCA) in Austria
      during the year 1994. This is a reduction of 3.2% concerning CA and an 8.6%
      increase in PTCA compared to 1993. 48% of all PTCAs were done during the
      diagnostic study (CA), multivessel PTCA in 11%, direct PTCA for ongoing
      infarction in 2.3%. Concerning "new devices", 437 stents (182 during the year
      1993) were implanted in 1994; also all 73 cases with rotablator, 105 with
      intracoronary ultrasound, and 26 directional coronary atherectomies (DCA) are
      documented. Hospital mortality after PTCA was 0.5% (unchanged from the years 1992
      and 1993), emergency bypass surgery rate after PTCA was 1.2% (0.7% during the
      year 1993), and 1.4% of the patients suffered a myocardial infarction in the
      cathlab (1.2% during 1993). International comparison shows Austria among the top
      nations with 2637 CA and 617 PTCA per million inhabitants, corresponding to a
      ratio of 23% PTCA per 100 CA. Risk adjustment (exercise stress test pre PTCA
      documented in six cath-labs in 1993, compared to 11 in 1994. Type of stenosis (A,
      B, C) in five labs in 1993 and in 12 labs in 1994) and outcome control (exercise
      stress test 3 months after PTCA documented in five cath-labs in 1993, compared to
      10 in 1994) are subject to constant improvement of our yearly monitor visits and
      feedback reaction. Austria is the only nation worldwide to support a complete
      national database with controlled numbers and parameters since more than 3 years,
      including yearly monitor visits (Internet address for the 1995 data:
      http@info.uibk.ac.at/gin/org/i_iik.stu/i_iik+ ++.htm) and feedback reports. We
      experienced no single negative reaction to our activities, but find them
      necessary for further quality management targets.

PMID- 8992806
TI  - [Initial clinical and angiographic results with the AVE Micro-Stent].
AB  - The AVE Micro Stent is a flexible stent with a small surface. Aim of this study
      was to investigate safety and efficacy of this stent. 105 AVE Micro Stents were
      deployed in 78 lesions in 64 patients. The implantation was performed electively
      (19%), after unsatisfactory PTCA (59%), and as "bailout" (23%) into left main
      (1), LAD (23), LCX (15), RCA (19) or CABG (6). Minimal lumen diameter and percent
      diameter stenosis were measured by quantitative coronary angiography before and
      after interventions and, in 21 patients, after 3 months. Stent-implantation was
      successful in 62 of 64 patients. The passage of the AVE Micro Stents through
      deployed stents (46) was successful in all of 28 cases. There were no deaths or
      myocardial infarctions. In two patients, subacute thromboses with subsequent
      increase of CK occurred, which were successfully treated. The minimal lumen
      diameter was 0.77 +/- 0.62 mm before intervention, 2.98 +/- 0.48 mm after
      implantation (p < 0.001), and 2.03 +/- 1.21 after 3 months (p < 0.001). The
      percent diameter stenosis was 75 +/- 20% before intervention, 39 +/- 20% after
      PTCA and 0 +/- 12% after implantation (p < 0.001). After 3 months, six of 21
      patients (29%) with follow-up angiography had a restenosis, defined as > 50%
      diameter stenosis compared with the reference vessel. CONCLUSIONS: 1) The AVE
      Micro Stent is a flexible stent, which can be safely and efficiently deployed
      even through implanted stents. 2) The AVE Micro Stent appears to be particularly
      suitable for "bailout" therapy of dissections. 3) The rate of subacute thrombosis
      was low with this stent.

PMID- 8992808
TI  - [Hypercoagulation caused by heparin-associated type II thrombocytopenia].
AB  - The immunological type of heparin-associated thrombocytopenia (HAT II) is a
      severe complication of heparin treatment and is associated with arterial and
      venous thrombosis. Only patients with absolute thrombocytopenia have prompted
      suspicion of HAT in clinical practice. We report on a 44-year-old male who
      developed thromboembolic episodes after coronary angiography such as reinfarction
      and thrombotic episodes of A. brachialis. Fibrinolytic therapy combined with i.v.
      unfractionated heparin treatment was the therapy of choice and was followed by
      severe further thromboembolic adverse effects. Besides an impaired fibrinolytic
      response and elevated antiphospholipid antibodies, we diagnosed HAT type II in
      HIPA and ELISA (Stago. Boehringer-Mannheim). This special patient had platelet
      counts within a normal range, when developing the thromboembolic episodes. It
      appears that the normal platelet count during the thromboembolic episodes reflect
      a relative thrombocytopenia. From a clinical point of view we recommend the use
      of a lab panel to exclude HAT type II in patients with thromboembolic episodes
      under therapy with fractionated or unfractionated heparin. Platelet counts within
      a normal range are not absolute exclusion criterion for HAT II.

PMID- 8992809
TI  - [Thrombus age as a determinant of lysis efficacy of in vitro produced platelet
      fibrin thrombi].
AB  - Thrombus age as a determinant of lysis efficacy has rarely been investigated. We
      developed an in vitro model to study the lysis of collagen induced platelet
      fibrin-thrombi of different ages. Histologically, the thrombi were similar to
      those found in coronary vessels of patients deceased from acute myocardial
      infarction or unstable angina. After 10 (TA10), 30(TA30) und 60 (TA60) min of
      thrombus aging thrombolysis over 30 min with urokinase alone or in combination
      with prostaglandin E1 was started. The efficacy of lysis with urokinase alone
      decreased with increasing thrombus age. After 30 min of lysis with urokinase
      alone weight of TA10-thrombi was reduced by 16.4 +/- 1.2 mg, of TA30-thrombi by
      11.5 +/- 0.9 mg (p < 0.001 vs TA10-thrombi) and of TA60-thrombi by 7.8 +/- 1.1 mg
      (p < 0.001 vs TA30, p < 0.0001 vs TA10-thrombi). The addition of prostaglandin Ei
      augmented lysis of TA10-thrombi, after 30 min of lysis thrombus weight was
      reduced by 17.3 +/- 1.2 mg (p < 0.01 vs urokinase alone). Lysis of 30 and 60 min
      old thrombi was nearly unaffected. Thus, thrombus age is a strong predictor of
      lysis efficacy of in vitro collagen induced platelet-fibrin-thrombi.

PMID- 8992810
TI  - [Acute type A dissection of the ascending aorta after aortocoronary bypass
      operation].
AB  - A 63-year-old man with a history of hypertension and coronary artery bypass
      grafting (1 year ago) was admitted with acute onset severe chest pain suggesting
      bypass dysfunction. Biplane cineangiography revealed acute aortic dissection
      Stanford Type A without involvement of the aortic valve, the coronary arteries or
      the proximal anastomoses of the two venous bypass grafts, one of which was
      occluded. Urgent repair of the aorta by a prosthesis and reinsertion of the
      patent venous graft in the innominate artery by interposition of saphenous vein
      was performed without complications. Sixteen months later on routine follow-up a
      pseudoaneurysm of the ascending aorta surrounding the aortic prosthesis was
      discovered by transesophageal echocardiographic examination. Reoperation was
      performed with prosthetic replacement of the ascending aorta. The operative
      course and further follow-up of now 1.5 years were uneventful.

PMID- 8992811
TI  - [Interventional coronary revascularization in a patient with chronic dissection
      of the ascending aorta].
AB  - In a 74-year-old patient who had undergone coronary artery bypass grafting 8
      years earlier, angiography was performed for recent onset of angina pectoris.
      Surprisingly, angiography revealed chronic dissection of the ascending aortic
      vessel with occlusion of a saphenous vein graft and partial thrombosis of the
      false lumen. Additionally, there was significant progression of coronary artery
      disease with new stenoses in both the ostium and body of the saphenous vein graft
      to the right coronary artery and a high grade left main coronary artery stenosis.
      Because any surgical intervention was refused by the patient, an interventional
      therapeutic strategy with percutaneous transluminal dilatation and stenting of
      both the bypass graft and the left main coronary artery was planned and
      successfully performed. This is the first report of a complex intervention and
      revascularization procedure carried out in a patient with type A aortic
      dissection. Thus, selected cases of chronic type A dissection my be amenable to
      interventional coronary revascularization in acute coronary syndromes.

PMID- 8992812
TI  - [Validity of telephone ECG multichannel transmission].
AB  - Transtelephonic ECG transmission is an established monitoring system for cardiac
      patients in many countries around the world with the exception of Germany. This
      study reports first experiences with a multichannel ECG system using nine leads.
      This system allows to analyze ECG for ischemic events in addition to cardiac
      arrhythmias. In this study the reliability of a modified lead registration
      procedure of the telephonic ECG system David 9 (MAP, Munchen) was compared to
      conventional 12-lead ECG recording (Mingograph 7, Siemens) in 225 consecutive
      patients. Comparison was performed using the arm electrodes of the telephonic ECG
      system (Tel. ECG) within the armpit (group I) or at the wrists (group II).
      Placing the electrodes at the wrists improved sensitivity and specificity of
      electrocardiograpic abnormalities to conventional 12 lead ECG (Conv. ECG).
      Specificity for detection of anterior myocardial infarction was 0.95 (Tel. ECG
      vs. Conv. ECG), specificity was 1.0. For infero-posterior infarction these
      relations were 0.94 and 1.0 respectively. ST-segment changes have been detected
      in the Tel. ECG with 0.93 and 0.89 for specificity and sensitivity. The numbers
      of arrhythmia analysis were 1.0 and 0.7 for all rhythm disturbances. Detection of
      atrial fibrillation was less reliable due to short recording time and low
      amplitude of the transmitted signal. Specificity and sensitivity for detection of
      ventricular arrhythmias were 1.0 and 0.89. Optimizing the placement of arm
      electrodes to the wrist instead of armpits as done up to now improved the
      reliability of the telephonic transmitted ECG. This telephonic ECG system then
      enables a reliable registration of ischemic and arrhythmic events.

PMID- 8992813
TI  - [Automatic report documentation in cardiology using a speech recognition system].
AB  - Computer systems that can convert spoken text into written text have recently
      become available. In one such system, the phonetics of spoken words are compared
      with those of 32 000 stored words, with a statistical program helping to choose
      the word with the highest probability of being correct. We evaluated the
      practicability of the IBM Voice Type system for writing medical reports using a
      cardiologic vocabulary. A total of 200 medical documents were generated with a
      mean of 301 +/- 52 words. In the mean, 12 +/- 5 words were falsely recognized in
      each document, resulting in a rate of correct recognition of 95.1 +/- 2.5%. It is
      possible to correct a falsely recognized word by choosing an alternative word
      from a provided list, which worked in our case in 51% (6.1 +/- 2.8 words in each
      document). Correction of falsely recognized words had to be done by manual input
      49% of the time (5.9 +/- 2.9 words in each document). The mean time demand for
      word correction amounted to 57 +/- 15 s for each document, whereas correction by
      manual input needed more time (37 +/- 14 s) than choosing from a list of
      alternative words (20 +/- 4s). A requirement for use of the Voice Type system is
      a reduced speech rate. Dictation of our documents took on average 260 s when done
      with a normal speech rate, and 400 s when done at a reduced speech rate. In
      conclusion, automatic writing of cardiologic reports can be done easily and with
      a low failure rate using the IBM Voice Type system with a cardiologic vocabulary.
      It takes about 3 min longer to create a medical text 1 1/2 pages long which is
      free of mistakes by using the Voice Type system than to simply dictate the text.
      Time can be saved by eliminating the need to check a preliminary report. The
      major advantage of automated reporting is that the written report is immediately
      available. For each discipline, specific vocabularies should be validated.

PMID- 8992814
TI  - [28th Annual meeting of the German Society of Pediatric Cardiology. Leipzig, 5-8
      October 1996. Abstracts].

PMID- 8992815
TI  - [Risk of thrombosis with oral contraceptives].

PMID- 8992816
TI  - [The early placental trophoblast. I. Normal development and endometrial and non
      tumor-induced disorders].
AB  - The development of the hemochorial placenta requires, that the trophoblast
      invades the endometrium, penetrating into its deep layers and blood vessels.
      Placental tissue includes components from two haplodifferent organisms, the
      mother and the fetus. Early steps in trophoblastic development are the adhesion
      and apposition. Invasion is an active process and correlations are observed
      between cellular invasivness and proteinase production, like uPA, tPA and its
      inhibitors, for example PAI-1. The process of trophoblast invasion is based on a
      complex interaction between the trophoblastic cells, various types of matrices
      and decidual as well as endometrial cells. Immunologic processes, like the
      production of blocking factors, paraimmune mechanisms and other HLA-dependent
      processes play an important role. During implantation a differentiation of
      trophoblastic cells takes place. The syncytiotrophoblast is the active cell of
      the invasive previllous trophoblast. The intermediate trophoblast plays this role
      concerning the villous trophoblast. The different trophoblastic cells are
      characterised by distinct morphologic and immunohistochemical features.

PMID- 8992817
TI  - [Laparoscopic para-aortic and pelvic lymph node excision--initial experiences and
      development of a technique].
AB  - It was the aim of this study to establish and analyze the laparoscopic technique
      of para-aortic and pelvic lymphadenectomy. During a one year period (from August
      1994 till July 1995) 42 patients underwent pelvic and para-aortic laparoscopic
      lymphadenectomy. In 29 cases cervical cancer, in 11 cases endometrial cancer and
      in 2 cases tumors of low malignant potential of the ovary were the indication for
      lymphadenectomy which was combined with radical vaginal hysterectomy in 19
      patients or simple vaginal hysterectomy in 13 patients. During the observation
      period the mean operating time for para-aortic and pelvic lymphadenectomy
      decreased and the efficiency of the lymphadenectomy increased significantly: the
      mean operating time for the first 10 para-aortic lymphadenectomies was 52 minutes
      and for the pelvic lymphadenectomies 141 minutes, respectively. For the last 10
      procedures the para-aortic part took 35 minutes and the pelvic part 110 minutes.
      Whereas at the beginning of the study a mean of 25 lymph nodes were removed, a
      mean of 36 lymph nodes were sampled during the last 10 procedures. In 3 patients
      operative injuries to major vessels were encountered of which two were followed
      by laparotomy. In 3 other patients laparotomy due to postoperative hemorrhage was
      necessary. These 6 complications occurred during the first half of the study and
      were not encountered during the following operations by changing from monopolar
      to bipolar coagulation and by modifying the regimen for perioperative thrombosis
      prophylaxis. In the first half of the study in 9 women blood transfusions were
      necessary and in the second half only 4 patients had to be transfused. In the
      first 10 patients the mean intraoperative blood loss was 1300 cc, in the last 10
      patients 300 cc. After a short learning curve laparoscopic para-aortic and pelvic
      lymphadenectomy is a safe and effective technique for staging cervical,
      endometrial, and early ovarian cancers. Though this technique is no standard
      procedure results of this pilot study warrant prospective studies comparing this
      technique with conventional procedures.

PMID- 8992818
TI  - [Diagnostic laparoscopy with mini-optics--initial experiences].
AB  - The use of a 1.2 mm microendoscope is compared to the conventional laparoscopy
      technique in this study. In 22 sterility patients and 23 patients suffering from
      chronic pelvic pain the high diagnostic value of the microendoscope is shown.
      Only in one case endometriosis (EEC I) is overseen. The diagnostic laparoscopy by
      the microendoscope is a new minimal invasive procedure which could be important
      as a screening method in future.

PMID- 8992819
TI  - [Incidence distribution of postoperative adhesions after using different
      coagulation techniques. An animal experiment study].
AB  - This study compares the incidence of adhesions after using the Endocoagulator by
      Semm with the incidence of adhesions after using the Nd-YAG-laser with 30 watts
      and 100 watts. At a total of 100 female Wistar-rats both, the uterine-horns and 2
      correspondent spots at the ventral abdominal-walls were coagulatet. resp.
      vaporized. After 14 resp. 28 days a relaparotomie was made: 1. With the Nd-YAG
      laser (30 and 100 watts) (significant) adhesions were found, at the uterine-horns
      in 100% of all cases with the Endokoagulator in 50%. At the peritoneal spots with
      the Nd-YAG-laser (30 and 100 watts) (not significant) adhesions were found in 10%
      of all cases, with the Endokoagulator 5% were found. 2. In addition to the
      macroscopic results histologic researches were also made: It was shown, that the
      treatment with Nd-YAG-laser develops a high grade of carbonisation-waste, which
      is known to be a main cause for the development of adhesions. 3. The division in
      14- and 28-day-groups showed no significant differences in the incidence of
      adhesions. 4. There were found more significant adhesions at the uterine-horns
      than at the peritoneal-spots.

PMID- 8992820
TI  - [Diagnostic value of color Doppler ultrasound in addition to B-image ultrasound
      in predicting underweight newborn infants].
AB  - In 74 pregnancies suspected for a small-for-gestational age (SGA) fetus by
      ultrasound measurement of the abdominal circumference, Doppler measurements of
      the fetal aorta and umbilical artery were performed. The renal and middle
      cerebral arteries were studied by color flow mapping. 47 infants were indeed
      growth retarded. The resistance- (RI) and pulsatility-indices (PI) of all vessels
      and their ratios were calculated. The superior parameter evaluated by receiver
      operating characteristic was the ratio of the PI of the middle cerebral artery in
      comparison to the PI of the umbilical artery at a threshold value of 1.6. An
      additional diagnostic value of Doppler sonography was only seen in cases of
      normal amniotic fluid volume and fetal symmetry, but not in cases of
      oligohydramnion and fetal asymmetry.

PMID- 8992821
TI  - [Pregnancy and extreme myomatous uterus--conservative management].
AB  - The management of a pregnancy complicated by uterus myomatosus remains being
      controversially discussed. Myomectomy early in pregnancy is opposed by
      exspectative management with myomectomy subsequent to the post partum period.
      Therapeutic abortion and exstirpation of the gravid uterus represent only
      hypothetical but not reasonable alternatives. Complications like ureteral
      obstruction, sepsis, and torsion of the uterus with subperimetrial bleeding as a
      cause of fever of unknown origin may occur. Rapid growth of a fibromatous uterus
      in pregnancy may call for a biopsy. Two cases are presented to demonstrate that
      with intensive pregnancy surveillance exspectative management is justified and
      may lead to successful confinement of the pregnancy.

PMID- 8992822
TI  - [Multiple liver abscesses in long-term intrauterine device].
AB  - We report on two cases of multiple hepatic abscesses caused by sever pelvic
      inflammatory disease secondary to intrauterine device. Such complication have
      previously been reported only twice. The course of the diseases were non
      specifically for a long time. As causative agent we isolated Klebsiella
      pneumoniae in the first case and in the other Fusobacterium necroforum. The
      patients were cured with combined operative and medical therapy.

PMID- 8992823
TI  - [Cluster headache: a description of a clinical case and the pathogenetic
      aspects].

PMID- 8992824
TI  - [Autonomic disorders in Parkinson's disease].

PMID- 8992825
TI  - [The ultrastructure of the neurons and interneuronal contacts of the hypothalamus
      in acute ethanol poisoning].

PMID- 8992826
TI  - [Phototherapy in neurology and psychiatry].

PMID- 8992827
TI  - [The psychophysiological specificity problem in panic attacks].

PMID- 8992828
TI  - [The psychopathological structure of depressions].
AB  - The theoretical model of depression has been developed on the basis of 275
      psychopathological observations of the affective disorders. The primary symptom
      complexes of hypothymia and alienation are considered to be the obligatory
      components of the syndrome structure. Depressions are ranged into the system with
      variants according to comorbid correlations between hypothymia and alienation.
      The anesthetic depression (in which the signs of vital affective suppression and
      alienation are characterized by total symptomatological comorbidity) considered
      to form the center of such system. The variations of affective disorders (vital,
      existential, "self-torture" depressions, "depression without depression") in
      which the comorbidity phenomenon is just partly realized and in which one of the
      symptom complex is totally expressed have the marginal position.

PMID- 8992829
TI  - [Periodic dystonia].
AB  - 20 authors' personal observations of periodic dystonia, a rare neurological
      syndrome, are presented. Main clinical manifestations are discussed in detail:
      the age of the disease debut, provoking factors, duration and frequency of the
      fits, the motor pattern, daily distribution of paroxysms. The comparison with
      analogous literary data is given too.

PMID- 8992830
TI  - [Autonomic regulation of cardiac activity and the status of central hemodynamics
      in patients with idiopathic mitral valve prolapse].
AB  - The vegetative regulation of heart rhythm was estimated from mathematical
      analysis of heart rhythm in 79 patients with prolapse of mitral valve (PMV) and
      in 15 patients with abnormal position of chordae (ADC). The sympathetic tone
      elevation was more typical for patients with HMV. Meanwhile the decrease of
      sympathetic tone was observed in patients with PMV and ADC with vegetative crises
      in anamnesis. The hyperkinetic type of blood circulation was revealed both in
      patients with PMV and ADC.

PMID- 8992831
TI  - [Dreams in neuroses in children and adolescents].
AB  - 46 children and adolescents with different forms of neuroses at the age of 10-18
      years were observed. It is shown that the dreams in neurotic individuals are
      characterised by both cognitive and affective activation as well as by widening
      of the limits of time and space, by frequent incompletion and by some imperative
      tendencies (the "channelization" of colour perception, repeated dreams' rise).
      There was a dependence of dream's character upon the neurosis form. The data
      obtained are important for adequate diagnosis and therapy of borderline
      conditions.

PMID- 8992833
TI  - [Clinico-neurophysiological correlations in migraine].
AB  - The more accurate definition of the role of cerebral mechanism in migraine
      development by means of contingent negative deviation (CND) method was the aim of
      this investigation. The significant alterations of some parameters were revealed
      in patients with migraine between the fits as compared with controls. The same
      indices were normal during the very fits. The CND indices were similar in
      patients with chronic Headache of strain and healthy individuals. The clinical
      neurophysiological analysis didn't reveal any significant dependence of CND
      changes clinical peculiarities and anxious and depressive disorders. The
      significant elevation of CND parameters observed between the attacks suggests
      presence of superfluous activity in cerebral structures (noradrenergic mainly) in
      patients with migraine without aura. Such alterations in their action lead,
      apparently, to headache attack development.

PMID- 8992832
TI  - [The characteristics of the manifestation of extraversion and neuroticism in the
      families of schizophrenia patients].
AB  - 40 schizophrenic patients, their 40 healthy relatives as well as 40 healthy
      control individuals without any hereditary predisposition to mental disease were
      examined by means of H. Eysenck questionnaire according to Extraversion,
      Neuroticism and Lie scale. Schizophrenic patients had higher ratings on the
      Neuroticism scale while their relatives were more extraverted as compared with
      controls. Both the patients and their relatives had higher ratings on the Lie
      scale. Genetic mathematical analysis revealed that the hereditary contribution to
      determination of these signs did not exceed 4%. It was suggested that personal
      peculiarities have influence on the realization of hereditary predisposition and
      that the very peculiarities may be transformed under the influence of either this
      predisposition or disease.

PMID- 8992834
TI  - [The electrophysiological characteristics of brain function in mental disorders
      in participants in the cleanup of the aftermath of the accident at the Chernobyl
      Atomic Electric Power Station].
AB  - 150 liquidators who had worked in the Chernobyl accident area were examined. All
      of them had mental diseases. Both alpha-rhythms disorganisation and increase of
      beta-1 activity were usually observed in brain cortex sensomotor areas of 43
      patients as compared with 17 healthy individuals. Meanwhile alpha-activity was
      significantly decreased especially in the left hemispheres of patients with
      psycho-organic syndrome. The majority of patients were characterized by both
      enhanced reaction to light flashes rhythm assimilation and the decrease of
      nonspecific and skin-galvanic reactions to the light stimulus. The conclusion is
      made about the systemic CNS damage in such patients that was more pronounced in
      psycho-organic syndrome.

PMID- 8992836
TI  - [Headache].
AB  - The basic pathogenetic mechanisms of the development of the main forms of
      headache, namely the migraine (M) and the tension-type headache (TTH) are
      discussed. In migraine are examined alterations in three important links such as
      the states of brain, peripheral vessels, and trigeminal system both between the
      fits and during the attacks. Factors provoking the attacks were considered too.
      The modern scheme of TTH pathogenesis was described. Main unsolved problems of M
      and TTH pathogenesis and therapy are also presented.

PMID- 8992835
TI  - [The validation of a method of dynamic proprioceptive correction for the
      rehabilitative treatment of patients with the residual stage of infantile
      cerebral palsy].
AB  - A new rehabilitation therapy's method was applied in the treatment of patients
      with infantile cerebral paralysis in the residual stage. The method is based on
      the proprioceptive correction by means of "Adelie-92" device, the modification of
      spaceman's overalls, which is used in conditions of weightlessness. The device
      allows to intensify the afferent proprioceptive flow which controls the motility
      through the central structures and to normalize it to some extent. A positive
      clinical effect was observed in 70% of cases. It manifested in appearance of both
      walking capacities and self-service ability.

PMID- 8992837
TI  - [New approaches to the rehabilitation of patients with neurological motor
      defects].
AB  - The results of the application of medical space suit "Adelie-92" for
      rehabilitation of patients with motor disorders are presented. Brain circulation
      acute disturbances as well as craniocerebral traumas were the main causes of
      these motor disorders. The complex estimation of patients condition was carried
      out both before and after the treatment. It included clinical data, physiological
      tests, EEG and evoked potentials investigations, stabilography and cardiorhythm
      analysis. The results proved the high effectiveness of the new therapeutical
      method.

PMID- 8992838
TI  - [The effect of Lendormin (brotizolam) on the sleep structure and subjective
      assessment of sleep in insomnia patients].
AB  - The influence of Lendormine (diazepine derivative) both on the sleep structure
      and subjective estimation of sleep was examined in 25 patients at the age of 19
      64 years old with neurotic insomnia. The investigation was performed before,
      during and after 10 days of treatment (0.25 mg before the sleep time). The drug
      administration resulted in significant improvement of sleep structure that is in
      sleep duration and efficiency because the drug either promoted falling asleep or
      increased the second and the forth stages of sleep. Lendormine decreased also the
      wakening time inside the sleep. The polysomnographic results coincided completely
      with subjective estimation of sleep by patients themselves after the treatment.
      The optimal time of therapy didn't exceed 2 weeks. The drug was well tolerated
      without any complications. The conclusion is made about high effectiveness of
      Lendormine in the treatment of patients with insomnia.

PMID- 8992839
TI  - [The treatment with the antidepressant Lerivon of tension headaches and autonomic
      crises].
AB  - 20 patients with vegetative crises (panic attacks) and 20 patients with tension
      type headache were treated by Lerivon (tetracyclic antidepressant)
      administration. The following parameters were investigated: the degree of
      headache expression according to visual analogous scale, the vegetative crises
      frequency and depression gravity by means of Spilberg test, the depression
      intensity by means of Back scale. The areas of different components of contingent
      negative deviation (CND)-early, late, postimperative negative waves as well as
      total CND area-were examined either. Both high clinical effects of the
      preparation and normalisation of psychophysiological parameters were found. 30 mg
      was the common daily dose for the patients with psychophysiological disorders.
      The clinical effect was observed quickly (7-10 days). The patients tolerated drug
      administration well, the sleepiness was the only side-effect. Thus, Lerivon
      proved highly effective for the treatment of both psychovegetative and algesic
      disorders and had some advantages as compared with commonly used tricyclic
      antidepressants.

PMID- 8992840
TI  - [The phototherapy of parkinsonism patients].
AB  - 40 patients with idiopathic parkinsonism were treated by artificial white light
      (intensity--3300 lux) together with total or partial "drugs holidays". The
      patients with newly made diagnosis "parkinsonism" were treated too. Both before
      and after light therapy (LT) (10 light exposures) we performed estimation of the
      main clinical manifestations of the disease (in rating scales), psychological
      assessment (Back's depression rating scale), examination of motility (authors'
      own special computer program "Hand's Movement Test for Windows"). It was observed
      that LT resulted in a decrease of the severity of either rigidity or bradykinesia
      (but not the tremor) as well as it also decreased the depression gravity and
      improved the motor functions. LT facilitated the patients' capacity to tolerate
      "the drugs holidays". LT permitted to combine it with drug therapy as well as LT
      decreased the complications of DOPA-containing drugs (on-off-effects and dystonic
      hyperkinesias). LT may be used as monotherapy in patients with initial
      manifestations of the disease. LT didn't cause any complications and was quite
      simple in carrying out. The conclusion is made about the perspectivity of LT
      application in parkinsonism treatment as important non-drug therapy.

PMID- 8992841
TI  - [The phototherapy of psycho-autonomic disorders].
AB  - 26 patients with psychovegetative disorders of neurotic origin (vegetative
      dystonia syndrome, hyperventilation syndrome, panic attacks, headache, insomnia,
      motivation disorders) were treated. Light therapy (LT) was carried out every day
      during 2 weeks. The light of 4500-5000 lux was applied during 1 hour (the
      distance-60 cm). As a result positive effect was revealed in 11 patients while
      there was no effect in 15 individuals. The positive effect was observed as a
      decrease of clinical manifestations. Patients with positive treatment results
      were characterised by short disease duration, weak hypothalamus dysfunction,
      astheno-depressive disorders prevalence. Negative effect of LT was observed in
      patients with longer duration of disease, more severe hypothalamic dysfunction
      together with anxious and astheno-hypochondriac syndrome. The conclusion a made
      that LT effect is associated with the character and the degree of
      psychovegetative disorders, but not with presence or absence of hypothalamic
      dysfunction.

PMID- 8992842
TI  - [The function of the segmental motoneurons in Wilson-Konovalov's hepatocerebral
      dystrophy].
AB  - 12 patients were examined by means of stimulative electromyography.
      Chronaximetric studies were carried out in 18 patients. The maximal amplitude of
      H-potential revealed the decrease of reflex excitability of the motoneurons pool.
      The stimulus value which is necessary for evoking H-reflex of liminal size
      testified the high reflex excitability of some alpha-motoneurons part. These
      motoneurons may take part in hyperkinesis development. The direct electrical
      excitability of motor units was elevated that was confirmed by motor response
      values. The motor analyzer functional rearrangement was revealed after
      stereotaxic operations as evidenced by dynamics of H-reflex and M-response
      parameters.

PMID- 8992843
TI  - [The functional activity of the lymphocyte subpopulations in patients with
      schizophrenia and schizoaffective psychosis].
AB  - The functional activity of natural killer (NK) and of T-helper (TH) lymphocytes
      was examined both in 19 patients with schizophrenia and in 6 patients with
      schizoaffective psychosis as well as in 93 control individuals. The patients were
      examined both before the treatment and two months after it. The cytotoxic level
      of NK lymphocytes was considerably decreased in all the patients before the
      treatment. The TH activity was decreased in 8 of 17 schizophrenic patients and in
      1 of 4 schizoaffective patients observed during the acute period. The increase of
      cytotoxic NK activity was seen in patients with schizoaffective psychosis after
      the treatment while such alterations in schizophrenic patients were absent. The
      TH activity changed neither in schizophrenic nor in schizoaffective patients
      after the treatment.

PMID- 8992844
TI  - [The factors affecting the mental health status and dynamics of the population].
AB  - The main factors having influence upon the state and the dynamics of mental
      health of population were considered on the basis of both literature data and
      authors own observations. The following groups of factors influencing either rise
      of psychical disorders incidence or their development as well as accumulation of
      patients in population were distinguished as well as corresponding
      epidemiological indices were identified too: 1) the level of psychiatric aid
      development, the principles of it organisation, 2) the inner conditions of
      diseases development, 3) social factors, 4) natural and anthropogenic
      environment.

PMID- 8992845
TI  - [The classification of headache].

PMID- 8992846
TI  - [The didactics of postgraduate training in psychiatry].

PMID- 8992847
TI  - [The criteria of nonorganic movement disorders].

PMID- 8992848
TI  - [Multisystem atrophy].

PMID- 8992849
TI  - [The Dandy-Walker syndrome in a child with the clinical picture of infantile
      cerebral palsy].

PMID- 8992850
TI  - Age-related occurrence of inhibitory antibodies to streptococcal pyrogenic
      superantigens.
AB  - Several bacteria, such as staphylococci and streptococci, can produce
      superantigens (SA) that induce the activation of T cells in humans. Although
      these organisms are the major causes of infection in children, the evidence that
      T cells are vigorously activated by SA produced by such organisms has not been
      reported except for toxic shock syndrome. In a previous paper, we demonstrated
      that inhibitory IgG antibodies (Ab) to SA in humans may protect against SA
      stimulation. In the present study, we investigated the occurrence of these
      inhibitory Ab to SA in 94 healthy children by the enzyme linked immunosorbent
      assay technique and the suppressive effect on T cell stimulation by SA. The
      positivity of Ab to streptococcal pyrogenic exotoxin (SPE)-A, SPE-C and
      staphylococcal enterotoxin B (SEB) increased with age. The age at which more than
      50% of children exhibited Ab to SA was 1 year for SEB, 6 years for SPE-C and 11
      years for SPE-A. Sera from these children were inhibitory to T cell proliferation
      elicited by SA in proportion to the concentration of IgG Ab to each SA. Sera
      supplemented with IgG Ab to SA by gamma-globulin therapy became inhibitory to T
      cell proliferation by SA. We conclude that, as children grow, they can develop Ab
      to SA that may play a role in protecting them against vigorous T cell activation
      by SA.

PMID- 8992851
TI  - Noonan syndrome and its related disorders.
AB  - The diagnosis of Noonan syndrome still rests on its clinical features. There are
      several syndromes to consider in the diagnosis of Noonan syndrome. These include
      cardio-facial-cutaneous syndrome, LEOPARD syndrome, neurofibromatosis-Noonan
      syndrome and Costello syndrome. The facial appearance and part of the clinical
      features of these syndromes are very similar to Noonan syndrome. Molecular
      research likely will elucidate whether these syndromes are variations of Noonan
      syndrome or etiologically different disorders.

PMID- 8992852
TI  - Bacterial changes in neonatal intensive care unit.
AB  - Organisms routinely cultured from throat swabs and infectious agents of sepsis
      and/or meningitis were reviewed. During the last 12 years, Klebsiella pneumoniae
      and Escherichia coli have been replaced by Staphylococcus aureus and Pseudomonas
      aeruginosa as the predominant isolates from throat swabs after admission. These
      change in the etiologic pattern of infectious agents of sepsis and/or meningitis,
      i.e., K. pneumoniae, E. coli, S. aureus, P. aeruginosa and staphylococcus
      epidermidis, were in agreement with the organisms isolated from the throat swabs
      after admission. The S. aureus isolated from throat swabs after admission showed
      a decrease in the bacterial activity of cloxacillin, cephazolin and cefotaxime
      since 1978.

PMID- 8992853
TI  - Follow-up study of auditory brainstem responses in hyperbilirubinemic newborns
      treated with exchange transfusion.
AB  - Changes in auditory brainstem responses (ABR) were studied and followed in
      hyperbilirubinemic newborns before and after exchange transfusion (ET), in order
      to check their usefulness in the early detection of acute and chronic bilirubin
      encephalopathy. ABR were measured in 10 newborns with marked hyperbilirubinemia
      (total bilirubin concentration [TBC] > or = 20 mg/dL, direct bilirubin
      concentration < 2 mg/dL) before and after ET. The means of birthweight,
      gestational age, and day of life on admission were 3267 g, 38.2 weeks and 3.4
      days, respectively. The ABR measurements were performed before ET and 6.0 days
      (the mean) after the ET. The follow-up of ABR was performed at 3 months of life.
      In comparison with the control values, the mean latencies of ABR were
      significantly prolonged (I, I-III, and I-V: P < 0.05) and the mean amplitudes
      were significantly decreased (I, III and V: P < 0.001) before ET. Significant
      improvement of ABR was noticed after the ET, especially in the shortening of the
      latency of wave I (P < 0.02) and in increasing the amplitudes of wave III and V
      (P < 0.02 and (P < 0.01, respectively), though the recovery of the latency of I-V
      (P < 0.02) and the amplitudes of I, III and V wave (P < 0.001, P < 0.001 and P <
      0.01, respectively) were delayed in comparison to the control. The follow-up data
      of ABR showed that, in two of nine infants (one was lost from the follow-up),
      there were still abnormal findings at 3 months of age. Only one of these, who
      prolonged the recovery of ABR until 5 years of age, developed a border
      intelligence. Though ET is effective for improvement of acute bilirubin
      encephalopathy with impaired ABR, a complete recovery of the ABR might be delayed
      in marked hyperbilirubinemia. The delay in improvement of ABR abnormalities might
      be possibly used as an early predictor for following chronic bilirubin
      encephalopathy.

PMID- 8992854
TI  - Serum cholesterol levels in school-aged Japanese children: the Hisayama study.
AB  - Hypercholesterolemia has been known to be an important factor in the development
      of atherosclelosis. Blood cholesterol screening and related health education in
      children, however, have not yet been widely practiced in Japan. From 1985 to
      1990, blood samples were obtained from 5825 school children aged 6 to 14 years
      residing in Hisayama, Japan. The mean total cholesterol (TC), triglyceride (TG),
      high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein
      cholesterol (LDL-C) levels were determined. The mean TC levels ranged from 155 to
      172 mg/dL for boys and from 156 to 170 mg/dL for girls, peaking at 9 years for
      both sexes. The TG levels also tended to increase gradually and to peak at 11
      years for both sexes. The tendency for TG levels to be higher was much clearer
      than in US children and adolescents. The HDL-C levels were highest at 9 years of
      age for both sexes and the LDL-C levels also tended to peak at 9 years of age for
      boys and at 8 years of age for girls. Atherogenic Indices [(TC-HDL-C)/HDL-C]
      ranged from 1.7 to 1.9 for boys and 1.8 to 2.0 for girls. As the cholesterol
      level of Japanese children would be expected to rise steadily reflecting their
      westernized lifestyle, preventive programes on a nationwide base including health
      education at school environments should be emphasized.

PMID- 8992855
TI  - Effects of high-dose intravenous methylprednisolone in children with acute
      rheumatic carditis.
AB  - In order to measure the effects of high-dose intravenous methylprednisolone
      (HIVMP) and compare its efficiency with that of oral prednisolone (OP), 18
      patients with active rheumatic carditis were studied. Ten patients received OP,
      while eight patients were treated with HIVMP. Clinical and laboratory responses
      to treatment were followed by sleeping pulse rate, systolic blood pressure,
      erythrocyte sedimentation rate (ESR), cardiothoracic ratio (CTR), PR interval on
      electrocardiogram, spectral and color flow imaging and Doppler echocardiographic
      findings; mitral and aortic regurgitant jet flow area, left atrial area, proximal
      width of mitral regurgitant jet area and regurgitation fractions. The results of
      patients in the HIVMP group showed statistically significant changes in ESR and
      CTR when compared with the patients receiving OP, and the recovery was more
      rapid. HIVMP therapy can be considered as a new method of treatment for acute
      rheumatic carditis.

PMID- 8992856
TI  - Insertion of a pacing lead via the tricuspid valve does not affect cardiac
      function and tricuspid valve regurgitation in young dogs.
AB  - A preliminary experimental study in dogs was conducted to evaluate the
      feasibility of transvenous cardiac pacing in the fetus with complete heart block
      associated with hydrops. Four young mongrel dogs were anesthetized with
      intravenous administration of sodium pentobarbital and mechanically ventilated,
      and a pacing lead was inserted via the tricuspid valve. The right ventricular
      cardiac output, aortic pressure and central venous pressure were measured, and
      the tricuspid valve regurgitation was measured semi-quantitatively using echo
      Doppler color flow imaging. The relationship between the location of the pacing
      lead and the tricuspid valve regurgitation and cardiac function was examined. The
      mean right ventricular cardiac output when the pacing lead was inserted into the
      superior vena cava (126 +/- 54 mL/min per kg) was not significantly different
      from that when it was inserted into the right ventricle (110 +/- 43 mL/min per
      kg). The aortic pressure was 66 +/- 7.7 mmHg and 67 +/- 6.6 mmHg, respectively,
      and the central venous pressure 5.9 +/- 1.7 mmHg and 5.7 +/- 1.6 mmHg,
      respectively, under the two conditions (not significantly different). The ratio
      of demonstrating significant tricuspid valve regurgitation was 4/13 into the
      superior vena cava and 5/13 into the right ventricle, respectively (not
      significantly different). The location of the pacing lead did not change the
      cardiac function or the amount of the tricuspid valve regurgitation in our
      experimental study. It was therefore concluded that the transvenous cardiac
      pacing technique has potential application in intrauterine transvenous cardiac
      pacing in the fetus with complete heart block.

PMID- 8992857
TI  - Hypoxanthine-guanine phosphoribosyltransferase gene analysis for Japanese
      patients with Lesch-Nyhan syndrome.
AB  - The Lesch-Nyhan syndrome results as a consequence of a severe deficiency of
      functional activity of purine salvage enzyme, hypoxanthine
      phosphoribosyltransferase (HPRT). We performed Southern blot analysis for five
      patients and their families using full length cDNA of the HPRT gene as a probe.
      Pst I digested Southern blot analysis revealed a large deletion that included
      exon 2 in patient 3. The size of this deletion was about 4.4 Kb. The mother of
      this patient had the same mutated allele and a normal one (heterozygote). This
      type of mutation from a Lesch-Nyhan syndrome patient has not been previously
      reported. The restriction fragment length polymorphism (RFLP) pattern was
      analyzed by Bam HI digested Southern blot analysis for one family who had no
      major gene abnormality. We determined from this analysis that the sister of the
      patient was a Lesch-Nyhan syndrome carrier and the fetus (brother) was normal for
      HPRT activity. This study shows RFLP analysis is still useful for carrier
      detection and prenatal diagnosis of Lesch-Nyhan syndrome.

PMID- 8992858
TI  - Psychosocial problems of children and adolescents with a chronic disease: coping
      strategies.
AB  - The purpose of this pilot study was to identify the coping strategies used by
      children, adolescents and youths with insulin dependent diabetes mellitus (IDDM)
      attending a camp for IDDM patients near Ryosen town, Fukushima Prefecture, Japan.
      Forty-three IDDM patients (24 females and 19 males) were studied, divided into
      two age groups. The first group included children (seven males and 10 females).
      The second group included adolescents and youths (12 males and 14 females). For
      the child group a projective drawing method was used for study and for the older
      group, an open questionnaire was used. Ryan-Wenger's taxonomy of children's
      coping strategies and Band's coding systems and classification were used for the
      content analysis. 'Instrumental action', 'Emotional expression' and
      'Catastrophizing thinking' were the coping strategies, represented in the child
      group. Gender differences in coping strategies were found in the group of
      adolescents and youths. The most often represented and most important coping
      category for the male subgroup was 'Behavioral avoidance'. Next in frequency of
      representation for the male subgroup were 'Cognitive distraction' and 'Behavioral
      distraction'. The coping categories 'Seeking social support' and 'Behavioral
      distraction' were represented with equal frequency in the female subgroup and the
      next was 'Aggressive activities'. The most important coping strategy for the
      female group was 'Talking to peers' from the seeking social support category. The
      study also helped to identify several children and adolescents who might need
      special psychological support.

PMID- 8992859
TI  - Acute disseminated encephalomyelitis associated with Mycoplasma pneumoniae
      infection.
AB  - An 8 year old girl with acute disseminated encephalomyelitis (ADEM) is described.
      Elevated serum antibody titers suggested recent Mycoplasma pneumoniae infection.
      T2-weighted image of magnetic resonance imaging (MRI) disclosed multiple lesions
      of high signal intensity in bilateral basal ganglia and thalami as well as in the
      white matter. Postcontrast T1-weighted image revealed an enhanced lesion in the
      deep white matter. She showed rapid clinical improvement in response to
      corticosteroid therapy. The lesions had disappeared completely on MRI performed
      10 weeks after the onset. ADEM is believed to be a demyelinating disorder of
      probable autoimmune etiology. MRI findings in this case may support the
      hypothesis that the primary pathological event is vascular injury and
      demyelination occurs only as a secondary phenomenon.

PMID- 8992860
TI  - A mother and daughter with agenesis of the corpus callosum.
AB  - A mother and daughter with agenesis of the corpus callosum are reported. There
      have only been 11 prior case reports of the familial occurrence of agenesis of
      the corpus callosum in the absence of extracranial malformations. Most of these
      reports have described familial occurrence among siblings. The present
      communication is only the second description of a parent and child with agenesis
      of the corpus callosum. A review of the published cases of familial syndrome
      unrelated agenesis of the corpus callosum indicates that both mental,
      developmental and neurologic disorders in cases involving parent and child are
      milder than those in cases involving siblings. Of additional interest,
      electroencephalography performed in this patient during sleep, frequently
      revealed bilateral asynchronous sleep spindles, supporting the hypothesis of
      previous investigators that the synchronicity of sleep spindles requires intact
      intercerebral commissures.

PMID- 8992861
TI  - Periventricular leukomalacia associated with hypocarbia.
AB  - We here report a case of periventricular leukomalacia (PVL) associated with
      hypocarbia which remained even after extubation. The patient had no risk factors
      affecting PVL development other than hypocarbia. We consider that the irregular
      tachypnea, which remained after extubation might be attributable to overdriving
      of ventilation of central neurogenic origin. Our patient's clinical course
      suggests that sodium bicarbonate drip infusion is a very effective way to alter
      the set point of respiratory neuronal drive of the patient with central
      neurogenic hyperventilation.

PMID- 8992862
TI  - Pericardial hydatid cyst with a fatal course.
AB  - Cases with cardiac hydatid cyst disease are uncommon, being approximately 0.2-2%
      of all cases. Most cardiac hydatid cysts are located in the interventricular
      septum or left ventricular wall. Pericardial location is very rare. We report on
      a 12 year old girl with pericardial hydatid cyst disease who was otherwise
      asymptomatic, having no cardiac symptomatology. Unfortunately the course of her
      disease was fatal. This is the first report of uncommon localized hydatid disease
      with a fatal outcome.

PMID- 8992863
TI  - Interruption of aortic arch type A in two siblings.
AB  - The recurrence of interruption of aortic arch (IAA) in siblings is rare.
      According to previous reports concerning siblings with IAA, all cases were IAA
      type B according to the classification proposed by Celoria and Patton. In this
      report we present the first cases of brothers with IAA type A. The type of IAA
      was confirmed by autopsy findings in the elder brother and by operative findings
      in the younger brother. The etiology of IAA was unclear. Monogenic inheritance
      was thought unlikely because congenital heart disease was not recognized in other
      members of the family. It would seem prudent to separate recurrence risks for IAA
      type A from IAA type B when genetic counselling is provided, but it must be borne
      in mind that the recurrence of IAA type A can occur among siblings.

PMID- 8992864
TI  - A case of Kabuki make-up syndrome with EBV+Burkitt's lymphoma.
AB  - Kabuki make-up syndrome was first reported in 1981 and is characterized by
      peculiar facies with post natal growth deficiency and mental retardation. Since
      the first report, approximately 100 cases have been reported, but there have been
      no reports of tumor development. A case is reported of a patient with Kabuki make
      up syndrome who developed malignant lymphoma in his abdomen at the age of 3
      years. The tumor was histologically diagnosed as Burkitt's lymphoma and Epstein
      Barr virus was detected by in situ hybridization.

PMID- 8992865
TI  - Segmental dilatation of the jejunum.
AB  - A 6 months old girl with segmental dilatation of the jejunum is described.
      Clinical findings were intermittent colic, severe pain and bilious vomiting,
      mimicking intussusception. At laparatomy dilated jejunal segment was encountered
      and resection performed. Histological examination showed normal ganglion cells
      with normal bowel structures. Postoperative course was uneventful.

PMID- 8992866
TI  - Hypercalciuria in renal glucosuria.
AB  - Primary renal glucosuria is a benign condition in which serum glucose level is
      normal. Idiopathic hypercalciuria is defined as increased urinary calcium
      excretion of more than 4 mg/kg/day in normocalcemic individuals in whom all known
      causes of hypercalciuria have been excluded. In this paper, we report on a case
      who has both renal glucosuria and hypercalciuria.

PMID- 8992867
TI  - Noonan syndrome: a clinical description emphasizing the cardiac findings.

PMID- 8992868
TI  - Evaluation of the therapy for streptococcal pharyngitis using Abbott Test Pack
      strep A.
AB  - A total of 953 children (511 boys and 442 girls) with streptococcal pharyngitis
      diagnosed with Abbott Test Pack Strep A (ATPSA) or throat cultures were analyzed.
      ATPSA specimens were repeatedly obtained until ATPSA turned negative during or
      after the treatment. The percentage of positive ATPSA specimens reached the
      lowest value (9.2%) on the fourth day of the course of the treatment, which
      indicates the acquisition from an infected individual is probably uncommon after
      the initial treatment. Bacteriological treatment failure (positive ATPSA after 14
      days of treatment) occurred in 4.1% of the children. Out of 953 subjects studied,
      216 (22.7%) had recurrent infections. More than 30% of the recurrent infections
      occurred within 2 months after initial infection. ATPSA is useful for
      establishing a rapid diagnosis and confirming the bacteriological success of the
      treatment.

PMID- 8992869
TI  - Cardiovascular abnormalities in Noonan syndrome: the clinical findings and
      treatments.
AB  - The clinical findings and treatment of cardiovascular abnormalities in 33
      patients with Noonan syndrome are reviewed. Major cardiovascular abnormalities
      were pulmonary valvular stenosis in 17 patients (51.1%), hypertrophic
      cardiomyopathy (HCM) in 11 (33.3%), and atrial septal defect in 9 (27.3%).
      Dysplastic pulmonary valve was seen in 6 (35.3%). Balloon pulmonary valvuloplasty
      was performed for 4 patients with dysplastic pulmonary valves. Two patients were
      successfully treated. Surgical treatment was performed in 13 patients, 11 alive
      and 2 died. Two patients with HCM and arrhythmia died suddenly. In conclusion,
      balloon pulmonary valvuloplasty should be the initial palliation for dysplastic
      pulmonary valve in Noonan syndrome, and HCM is the risk factor for sudden death
      in Noonan syndrome.

PMID- 8992870
TI  - Hypertrophic cardiomyopathy in Noonan syndrome.
AB  - Noonan syndrome, a well-known multiple congenital anomalies syndrome, is
      frequently accompanied by cardiovascular diseases including hypertrophic
      cardiomyopathy (HCM). The incidence of HCM in Noonan syndrome is approximately 20
      30% and one-third of cases reveal ventricular outflow obstruction. HCM in Noonan
      syndrome is occasionally associated with a congenital heart defect, whereas
      classic HCM seldom accompanies cardiac malformations. Asymmetric septal
      hypertrophy and symmetric septal hypertrophy (concentric hypertrophy) can be
      observed both in HCM with Noonan syndrome and in classic HCM, but apical
      hypertrophy has not been reported in Noonan syndrome yet, although it appears in
      classic HCM. Congestive heart failure is the major cause of death in patients
      with HCM in Noonan syndrome, but cases of sudden death have also been reported.
      The histopathologic findings of ventricular myocardial tissue in HCM with Noonan
      syndrome are similar to those in classic HCM.

PMID- 8992871
TI  - Growth hormone treatment in Noonan syndrome.
AB  - Growth responses to growth hormone (GH) treatment in Noonan syndrome are compared
      with those in short children with the other growth disorders. The responses in
      Noonan syndrome are much less than those in children with GH deficiency, a little
      less than those in children with non-endocrine short stature and almost the same
      as those in children with Turner syndrome. As it is speculated that GH induces
      puberty earlier that expected in Noonan Syndrome, the efficiency of GH treatment
      for final height in Noonan syndrome is not promising.

PMID- 8992872
TI  - Temporal expression of the anabolic action of PTH in cancellous bone of
      ovariectomized rats.
AB  - When administered intermittently, parathyroid hormone (PTH) is a potent anabolic
      agent in both human and animal bone. To improve our understanding of this
      anabolic effect, we have examined the time course of PTH action in an established
      animal model of estrogen deficiency-induced bone loss: the ovariectomized rat.
      Animals were ovariectomized (Ovx) and allowed to lose bone for 6 weeks. A dose of
      20 micrograms/kg/d of rat PTH (1-34) was administered s.c., 6 days each week for
      periods of 1, 2, 3, 4, 6 and 8 weeks. Animals were sacrificed for evaluation of
      skeletal histomorphometry of the proximal tibia and mechanical strength of the
      cancellous bone in the marrow cavity of the distal femur. Cancellous bone volume
      (Cn-BV/TV) increased gradually over 8 weeks of treatment (16.8 +/- 1.6 to 24.1 +/
      2.7%) as did the bone formation rate (0.308 +/- 0.054 to 1.659 +/- 0.293
      microns3/micron2/d), as determined by an increase in both total mineralization
      surface (15.5 +/- 2.1 to 42.7 +/- 5.0%) and mineral apposition rate (1.88 +/-
      0.20 to 3.55 +/- 0.39 microns/d). The largest increments in these variables
      reflecting bone formation occurred over the first week of treatment. This bone
      formation was accompanied by an increase in trabecular thickness (Tb.Th) (55.3 +/
      3.4 to 80.5 +/- 5.0 microns) without a corresponding increment in trabecular
      number (Tb.N) (3.65 +/- 0.17 to 3.55 +/- 0.26). Extensive tetracycline labels
      were visualized on the surface of trabecular rod-like and plate-like structures.
      A small transient, though not statistically significant, increase occurred in
      both eroded surface and urinary pyridinoline concentration immediately after the
      onset of PTH administration. Osteocalcin showed a small decrement in the first
      two weeks after PTH administration, but the levels were elevated when compared
      with the Ovx control in later weeks. Mechanical strength of the cancellous bone
      also increased significantly with PTH treatment (20.5 +/- 2.4 to 46.1 +/- 10.0
      Newtons). Our results showed that: 1) intermittent PTH treatment of Ovx rats
      elicited an immediate increase of bone formation activity by the existing
      osteoblasts, 2) the increase of Cn-BV/TV after PTH administration resulted
      primarily from an increase in Tb.Th, and 3) improved mechanical strength after
      PTH treatment can be achieved by increases in Tb.Th without an increase in Tb.N.

PMID- 8992873
TI  - Sequential effects of chronic human PTH (1-84) treatment of estrogen-deficiency
      osteopenia in the rat.
AB  - Although daily injections of parathyroid hormone (PTH) can rapidly reverse
      estrogen-deficiency bone loss in rats, PTH treatment of osteoporotic humans has
      to date produced more modest increases in bone mass. To explore the reasons for
      this important difference, we evaluated the dose- and time-dependence of human
      PTH 1-84 treatment effects on bone mass and biochemical markers of bone
      metabolism in rats with estrogen-deficiency bone loss. The highest doses of PTH
      increased spinal, femoral, and total skeletal mass to supra-normal levels and
      stimulated cortical endosteal bone formation. Spine and whole skeleton mass and
      density increased rapidly at first, but then increased more slowly; the rate of
      change decreased significantly (p < 0.01) during continued treatment with the
      highest doses of PTH. The effects of PTH treatment on biochemical markers also
      were both dose-dependent and time-dependent. Serum osteocalcin, a marker of
      osteoblast function, increased with the highest doses of PTH (p < 0.001), but
      reached an early plateau and later returned toward baseline. Urinary excretion of
      pyridinolines, a marker of osteoclast function, increased in a time-dependent
      fashion throughout treatment (p < 0.001). Serum 1,25(OH)2 vitamin D levels
      increased in a dose-related fashion, but then decreased toward control levels
      despite continued treatment. We demonstrate that both osteoblast and osteoclast
      function are increased during daily PTH therapy in the rat. The pattern of
      response depends on both the dose of PTH and the duration of therapy. These dose-
      and time-related effects should be taken into account when designing experimental
      PTH treatments for osteoporosis, and they deserve intensive study.

PMID- 8992874
TI  - PTH: a future role in the management of osteoporosis?

PMID- 8992875
TI  - Calcitonin prevents bone loss but decreases osteoblastic activity in
      ovariohysterectomized beagle dogs.
AB  - The antiresorptive effects of calcitonin are well documented. Recent in vitro and
      in vivo evidence points to an anabolic effect of calcitonin on osteoblasts. To
      assess the value of calcitonin in preventing the rapid and early bone loss after
      cessation of ovarian function and to investigate its effects on osteoblasts in
      vivo, 32 dogs were ovariohysterectomized (OHX) and 32 dogs were sham-operated
      (Sham). After the surgeries, half of the OHX and Sham dogs received every-other
      day subcutaneous injections of human calcitonin (0.25 mg/dog/d), and the
      remaining dogs were given vehicle. Half of the animals had a bone biopsy at week
      2 and were euthanized thereafter; the other half of the animals underwent a bone
      biopsy at month 1 and were euthanized at month 4. Blood drawings were done at
      baseline and at the time of each bone biopsy. Calcitonin prevented the increase
      in erosion depth seen in OHX animals and prevented the cancellous bone loss
      observed at 2 weeks and at 1 and 4 months. Calcitonin did not affect bone volume
      in Sham dogs. However, treatment with calcitonin induced a decrease in
      mineralizing surfaces and bone formation rates at the bone surface and cell level
      and an increase in mineralization lag time in both Sham and OHX animals without
      significantly affecting osteoblast number. This finding indicates that the
      negative effect of calcitonin on bone mineralization is not solely the result of
      a decrease in bone turnover. The data show that calcitonin, because of its
      antiresorptive effects, can prevent bone loss after cessation of ovarian
      function. However, short-term treatment with calcitonin does not stimulate
      osteoblast activity; on the contrary, it exerts a negative effect on osteoblastic
      bone formation and mineralization. Long-term studies are needed to investigate
      whether this unwanted effect of calcitonin on osteoblasts in vivo represents a
      transitory or persistent phenomenon.

PMID- 8992876
TI  - Effects of continuous calcitonin treatment on osteoclast-like cell development
      and calcitonin receptor expression in mouse bone marrow cultures.
AB  - Continuous treatment with calcitonin (CT) to inhibit osteoclastic bone resorption
      results in acquired resistance. The mechanisms of this "escape" phenomenon are
      not yet established. The aim of this study was to examine the effects of
      continuous treatment with CT on the generation of osteoclasts and calcitonin
      receptor (CTR) expression in mouse bone marrow cultures. This was done by daily
      CT treatment of mouse bone marrow cultures from day 0, when only undifferentiated
      mononuclear precursors of osteoclast-like cells were present, or commencing from
      day 6, when differentiated osteoclast-like cells were abundant. The response to
      CT treatment was determined by quantitation of cells positive for tartrate
      resistant acid phosphatase (TRAP) and binding of 125I-salmon CT. Calcitonin
      receptor and TRAP mRNA levels were determined using semi-quantitative reverse
      transcription/polymerase chain reaction. When cultures were treated with CT from
      day 0, TRAP-positive multinucleated cells appeared. These cells expressed only
      very low levels of CTR or CTR mRNA and were morphologically indistinguishable
      from osteoclast-like cells formed in control cultures. They also displayed the
      ability to resorb bone. Continuous CT treatment of cultures from day 6 rapidly
      reduced the CTR mRNA levels, with a t1/2 of 6 to 12 h, and these levels remained
      low thereafter. 125I-salmon CT binding capacity, as determined by
      autoradiography, was lost in parallel. These effects were specific for the CTR
      since there was no consistent effect on TRAP mRNA levels. Based on these data, we
      suggest that the "escape" phenomenon may result from a prolonged CT-induced loss
      of CT responsiveness due, at least in part, both to reduced synthesis of CTR, and
      to the appearance in bone of CTR-deficient osteoclasts.

PMID- 8992877
TI  - Ectopic secretion of osteocalcin, the major non-collagenous bone protein, by the
      myeloma cell line NCI-H929.
AB  - In this study we provide the first evidence that human non-osteoblastic cells
      secrete the bone-specific protein osteocalcin. We show that the myeloma cell line
      NCI-H929 constitutively produces low amounts of osteocalcin. Furthermore, we
      demonstrate that this production is strongly enhanced after 1,25(OH)2D3
      stimulation. An amplification or a deregulation of the osteocalcin gene could be
      responsible for the observed phenomenon because NCI-H929 has the unusual
      characteristic of having at least three chromosomes 1, where the osteocalcin gene
      was mapped (1q25-q31). It is of interest to note that the patient in whom the NCI
      H929 cell line originated never developed osteolytic lesions despite extensive
      disease apparent at autopsy. Although lytic bone lesions with low osteocalcin
      serum levels are a common feature of multiple myeloma (MM), a small subset of
      patients does not develop lytic bone lesions or even demonstrate osteosclerotic
      MM. This occurrence is associated with high osteocalcin serum levels of unknown
      origin. In this context, osteocalcin production by immortalized tumor lacking any
      osteolytic potential could be relevant to the pathophysiology of this particular
      type of MM.

PMID- 8992878
TI  - Increase of vascular endothelial growth factor mRNA expression by 1,25
      dihydroxyvitamin D3 in human osteoblast-like cells.
AB  - Vascular endothelial growth factor (VEGF), a secreted endothelial cell-specific
      mitogen, is produced in endocrine organs and regulated by trophic hormones.
      Because angiogenesis and osteogenesis are closely regulated, we studied whether
      human osteoblast-like cells produce VEGF, and if so, what factors regulate VEGF
      mRNA expression. Human osteoblast-like cells (HObLC) derived from trabecular bone
      explants were cultured in alpha-MEM supplemented with 10% fetal calf serum.
      Northern blot analysis revealed that HObLC expressed VEGF mRNA, as did several
      human osteosarcoma cells. 1,25-(OH)2D3 increased the steady-state levels of VEGF
      mRNA in a time- and concentration-dependent manner in HObLC and one of the
      osteosarcoma cell lines, SaOS-2, accompanied by an increase in the concentration
      of immunoreactive VEGF in the conditioned medium. PTH and IGF-I also increased
      the level of VEGF mRNA in HObLC and SaOS-2 cells. Furthermore, 12-O
      tetradecanoylphorbol ester stimulated VEGF mRNA in a time-and concentration
      dependent manner. The VEGF mRNA expression induced by 1,25-(OH)2D3 was completely
      inhibited by H-7, but only partially by staurosporine. We have demonstrated that
      PTH, IGF-I, and most potently 1,25-(OH)2D3 stimulate the mRNA expression and
      secretion of VEGF in human osteoblast-like cells, suggesting that one of the
      anabolic effects of 1,25-(OH)2D3 on skeletal tissue may be mediated by VEGF
      produced by osteoblasts.

PMID- 8992879
TI  - A digital model of trabecular bone.
AB  - A 3D microCT dataset of bovine bone was used to create a digital 3D model
      simulating trabecular bone. The model serves a dual purpose: It allows for
      standard quantitative histomorphometric analysis and it approximates the reality
      e.g. of high resolution CT in vivo datasets of trabecular bone. Thus the model
      can potentially be used as a reference to develop 2D and 3D structural analysis
      algorithms applicable in vivo while it simultaneously allows verification of the
      results of these algorithms by standard histomorphometry. The model can be used
      as a standard to evaluate the impact of image processing techniques and of
      restrictions of imaging systems on the quantitative analysis of structural
      parameters describing a trabecular network. The model can be used for a
      comparison of 2D and 3D structural analysis methods and for an analysis of
      decreasing spatial resolution. The effects of segmentation and filtration can be
      studied separately and grayscale analysis is possible. As examples standard 2D
      histomorphometry and the analysis of topological parameters like node number and
      trabecular network length were applied to the model. The influence of spatial
      resolution was investigated by decreasing the spatial resolution of the digital
      model. The bone surface area determined by 3D surface triangulation was only 4%
      smaller than the surface area determined from the traditional 2D bone
      histomorphometric parameter bone surface/tissue volume (BS/TV) when 2D results
      were averaged over all slices of the 3D volume. However, BS/TV showed large (10%)
      variations among slices within the volume. Both histomorphometric and topological
      parameters were heavily influenced by spatial resolution and image segmentation.
      Our initial experience with the digital model indicates a need to investigate
      bone microstructure based on volume data or to average the 2D results of many
      slices.

PMID- 8992880
TI  - Effects of unilateral strength training and detraining on bone mineral mass and
      estimated mechanical characteristics of the upper limb bones in young women.
AB  - The aims of this study were to examine the effects of 12 months unilateral high
      resistance strength training and 8-month detraining on bone mineral content
      (BMC), density (BMD) and estimated mechanical characteristics of upper limb
      bones, and also to estimate consequent loading induced strains on forearm bone
      shafts. Thirteen female physiotherapy students (mean 23.8 +/- 5.0 yrs, 166 +/- 7
      cm, 64.4 +/- 7 cm, 64.4 +/- 13.3 kg) trained their left upper limbs with
      dumbbells on average 2.8 times per week for 12 months, followed by eight months
      detraining. Nineteen students served as controls (mean 25.7 +/- 5.2 yrs, 165 +/-
      4 cm, 62.1 +/- 7.0 kg). BMC, BMD, and bone width and estimated cortical wall
      thickness (CWT) were measured at five different sites in both upper extremities
      (proximal humerus, humeral shaft, radial shaft, ulnar shaft, and distal forearm)
      using dual energy x-ray absorptiometry (DXA) scanner. In addition, cross
      sectional moment of inertia (CSMI) was estimated from DXA data. The maximal
      isometric strength of the upper extremities was measured with an arm flexion
      extension dynamometer. The training increased significantly the flexion strength
      by 14% (p = 0.001). During the detraining period, all measured strength values in
      the training group decreased in both limbs with respect to values after training.
      Despite the clear effect on muscular strength, no significant intergroup
      differences were observed in BMC, BMD, bone width, CWT, or CSMI values at any
      measured site after the training or detraining period. The estimated loading
      induced strains remained within customary loading, and the change in strain level
      was only 15%. In conclusion, this study indicated that using high-resistance
      strength training may not provide an effective osteogenic stimulus for bone
      formation and geometric changes in upper limb bones of young, healthy, adult
      women. The interaction of bones and muscles may play an important and relatively
      unrecognized role in the development of bone strength, suggesting that the entire
      biomechanical environment should be carefully considered when evaluating the
      osteogenic efficiency of physical loading.

PMID- 8992881
TI  - Mechanical loading and sex hormone interactions in organ cultures of rat ulna.
AB  - The separate and combined effects of loading and 17 beta-estradiol (E2) or 5
      alpha-dihydrotestosterone (DHT) on [3H]thymidine and [3H]proline incorporation
      were investigated in cultured ulna shafts from male and female rats. Ulnae were
      cultured and loaded to produce physiological strains in the presence or absence
      of 10(-8) M E2 or DHT. Loading engendered similar increases in incorporation of
      [3H]thymidine and [3H]proline in male and female bones. E2 engendered greater
      increases in incorporation in females than in males, and DHT greater increases in
      males than in females. In males E2 with loading produced increases in both
      [3H]thymidine and [3H]proline incorporation, which approximated to the arithmetic
      addition of the increases due to E2 and loading separately. In females E2 with
      loading produced increases greater than those in males, and substantially greater
      than the addition of the effects of E2 and loading separately. Loading with DHT
      in males also showed additional [3H]thymidine and [3H]proline incorporation. In
      females there was additional incorporation of [3H]proline, but not [3H]thymidine.
      The location of incorporation of [3H]thymidine and [3H] proline was consistent
      with their level of incorporation reflecting periosteal osteogenesis, in which
      case the early osteogenic effects of sex hormones are gender-specific when acting
      alone and in combination with loading. In males the effects of estrogen and
      testosterone add to, but do not enhance, the osteogenic responses to loading. In
      females testosterone with loading produces an additional effect on [3H]proline
      incorporation but no greater effect than loading alone on that of [3H]thymidine.
      In contrast, estrogen and loading together produce a greater effect than the sum
      of the two influences separately. Because premenopausal bone mass will have been
      achieved under the influence of loading and estrogen acting together, these
      findings suggest that the bone loss which follows estrogen withdrawal may result,
      at least in part, from reduction in the effectiveness of the loading-related
      stimulus on bone cell activity. This stimulus is normally responsible for
      maintaining bone mass and architecture.

PMID- 8992882
TI  - Constitutive expression of non-bone/liver/kidney alkaline phosphatase in human
      osteosarcoma cell lines.
AB  - Alkaline phosphatase (ALP) plays an important role in bone mineralization; high
      levels in differentiated osteoblasts allows their identification easily in vitro.
      It is generally assumed that the activity of ALP in osteosarcoma-derived cell
      lines commonly used in studies of bone cell biology is exclusively due to the
      bone/liver/kidney (BLK) isoenzyme. However, we noted that two human osteosarcoma
      cell lines, U-2 OS and U-393 OS, predominantly expressed a truncated 1.8 kb mRNA
      for BLK-ALP. This observation stimulated further investigation upon the ability
      of ALP to form functional protein. We found that, unlike the BLK-ALP of the Saos
      2 osteosarcoma cell line, the activity of U-2 OS ALP was thermostable, unaffected
      by L-homoarginine and levamisole, but inhibited by L-phenylalanine; these
      properties are characteristic of the placental and/or placental-like (PL-/PL-like
      ALP) isoenzymes which are 98% homologous at the amino acid level. In the U-393 OS
      cell line, which expresses the normal-sized 2.5 kb mRNA in substantially higher
      levels than that produced by U-2 OS cells, the ALP activity had kinetic
      properties very similar to that produced by the Saos-2 line for all criteria
      tested. The HOS osteosarcoma cell line (also known as TE-85), which express the
      normal-sized 2.5 kb BLK-ALP mRNA only, exhibited ALP activity with kinetic
      properties of both the BLK and PL-/PL-like isoenzymes. The three test lines, U-2
      OS, U-393 OS and HOS, produced PL-/PL-like ALP mRNA and protein constitutively,
      and levels of these increased in cells treated with 1 microM dexamethasone.
      However, dexamethasone treatment of cells did not alter the types of ALP
      isoenzyme expressed. Thus our results show that, like Saos-2 cells, U-393 OS
      cells produce active BLK-ALP exclusively, whereas U-2 OS cells produce PL-/PL
      like ALP only, and the HOS cell line produces both. Our findings have important
      implications for phenotypic characterization of various human osteosarcoma cell
      lines, and suggest that the production of PL-/PL-like ALP may be a more common
      occurrence in osteosarcomas than was originally thought.

PMID- 8992883
TI  - Effects of synthetic peptido-leukotrienes on bone resorption in vitro.
AB  - Peptido-leukotrienes are short-lived organic molecules known to have potent
      biological effects as mediators of inflammation, hypersensitivity and respiratory
      disorders. However, little is known concerning their effects on bone cells. We
      have shown previously that stromal cells isolated from a human giant cell tumor
      secrete 5-HETE (5-hydroxyeicosatetraenoic acid) and the peptido-leukotrienes,
      also known as the cysteinyl leukotrienes LTC4, LTD4, and LTE4. These eicosanoids
      were shown to stimulate the multinucleated giant cells obtained from these tumors
      to form resorption lacunae on sperm whale dentine. Here, we show that the peptido
      leukotrienes also stimulate isolated avian osteoclast-like cells to form
      resorption lacunae and to increase their content of tartrate-resistant acid
      phosphatase. LTD4 increased 45Ca release from murine calvarial bone organ
      cultures, but not from fetal rat long bone cultures. Isolated avian osteoclast
      like cells were chosen to perform receptor binding studies, as this population is
      the most homogeneous source of osteoclasts available. After the precursors had
      fused to form multinucleated cells, receptor binding assays were performed.
      Scatchard analysis of saturation binding data showed a single class of binding
      sites, with a dissociation constant (Kd) of 0.53 nM and a receptor density of
      5,200 receptors per cell. Competition binding studies showed receptor specificity
      using a specific LTD4 receptor antagonist ZM 198,615. These data show that the
      peptido-leukotrienes activate highly enriched populations of isolated avian
      osteoclast-like cells, and also that specific LTD4 receptors are present in this
      cell population.

PMID- 8992884
TI  - The heritability of bone mineral density, ultrasound of the calcaneus and hip
      axis length: a study of postmenopausal twins.
AB  - Population based studies have demonstrated that having a first degree relative
      with a hip fracture is predictive of future hip fractures. Postmenopausal bone
      mineral density (BMD), ultrasound of calcaneus and hip axis length are associated
      with hip fracture, with the association for ultrasound and hip axis length being
      independent of BMD. The aim of this study was to determine the genetic component
      of these three important risk factors. We performed a classical twin study using
      500 normal female twins, 128 identical and 122 non-identical pairs, aged 50 to 70
      years. We measured bone mineral density at multiple sites, hip axis length
      (distance from the inner rim of the acetabulum to the greater trochanter),
      broadband ultrasound attenuation and velocity of sound of the calcaneus. Bone
      density had a strong genetic component at all sites with estimates of
      heritability ranging from 0.46 to 0.84. Hip axis length and velocity of sound had
      major genetic components with estimates of 0.62 and 0.61 respectively, which
      remained virtually unchanged after adjustment for bone mineral density. Broadband
      ultrasound attenuation had a moderate genetic component with an estimate of 0.53,
      which was reduced further to 0.45 after adjustment for BMD. In summary, all three
      bone measurements, which are independently associated with hip fracture, are
      independently heritable. This study suggests that a combination of different
      genetic factors acting on the structure, dimensions and density of bone may
      explain the importance of family history as a risk factor for hip fracture.

PMID- 8992885
TI  - Human protein tyrosine phosphatase-sigma: alternative splicing and inhibition by
      bisphosphonates.
AB  - Two forms of the transmembrane human protein tyrosine phosphatase (PTP sigma),
      generated by alternative splicing, were identified by cDNA cloning and Northern
      hybridization with selective cDNA probes. The larger form of PTP sigma is
      expressed in various human tissues, human osteosarcoma, and rat tibia. The hPTP
      sigma cDNA codes for a protein of 1911 amino acid residues and is composed of a
      cytoplasmic region with two PTP domains and an extracellular region that can be
      organized into three tandem repeats of immunoglobulin-like domains and eight
      tandem repeats of fibronectin type III-like domains. In the brain, the major
      transcript of PTP sigma is an alternatively spliced mRNA, in which the coding
      region for the fibronectin type III-like domains number four to seven are spliced
      out, thus coding for a protein of 1502 amino acid residues similar to the rat PTP
      sigma and rat PTP-NE3. Using in situ hybridization, we assigned hPTP sigma to
      chromosome 6, arm 6q and band 6q15. The bacterial-expressed hPTP sigma exhibits
      PTPase activity that was inhibited by orthovanadate (IC50 = 0.02 microM) and by
      two bisphosphonates used for the treatment of bone diseases, alendronate (ALN)
      (IC50 = 0.5 microM) and etidronate (IC50 = 0.2 microM). In quiescent calvaria
      osteoblasts, micromolar concentrations of vanadate, ALN and etidronate stimulate
      cellular proliferation. These findings show tissue-specific alternative splicing
      of PTP sigma and suggest that PTPs are putative targets of bisphosphonate action.

PMID- 8992886
TI  - Establishment of bone morphogenetic protein 2 responsive chondrogenic cell line.
AB  - A clonal cell line named RMD-1 was established from the skeletal muscle of a 20
      day fetal rat. RMD-1 represents a morphologically homogeneous population of
      undifferentiated mesenchymal cells, expressing alpha-smooth muscle actin and type
      I collagen, but no cartilage-associated genes. When cultured in agarose gel
      containing 100 ng/ml of recombinant human bone morphogenetic protein 2 (rhBMP-2;
      BMP-2), RMD-1 cells formed colonies and showed chondrocyte-like features as
      assessed by their ultrastructure, metachromatic staining with toluidine blue, and
      the production of large hydrodynamic-size proteoglycans. RMD-1 cells also
      differentiated into chondrocytes when the cells were plated at high density (over
      2.5 x 10(5) cells/cm2) on type I collagen and incubated in medium containing 0.5%
      fetal bovine serum and 100 ng/ml of BMP-2. This chondrogenic differentiation was
      evidenced by a distinct morphological change into spherical cells, an increase in
      the levels of sulfated glycosaminoglycans, a decrease in type I collagen mRNA and
      the expression of cartilage-associated genes, including type II collagen, type IX
      collagen, aggrecan and alkaline phosphatase. In the presence of ascorbic acid and
      10% serum, RMD-1 cells increased in size and expressed type X collagen as well as
      high alkaline phosphatase activity, then induced matrix mineralization. Thus, RMD
      1 is a unique cell line that can differentiate from undifferentiated mesenchymal
      cells into hypertrophic chondrocytes.

PMID- 8992887
TI  - Doubling skeletal mass during adult life: the syndrome of diffuse osteosclerosis
      after intravenous drug abuse.
AB  - A former intravenous substance abuser, seropositive for hepatitis C virus
      infection, was referred for diffuse osteosclerosis. There was no history of
      fracture or skeletal deformity. Cortical and trabecular bone density was
      approximately twice the mean value for controls. Skeletal histology revealed
      dense lamellar bone. Recognized causes of acquired generalized osteosclerosis or
      hyperostosis were excluded. This patient verifies the syndrome of painful diffuse
      osteosclerosis after intravenous drug abuse and shows that skeletal mass can be
      markedly increased with histologically normal, structurally sound bone during
      adult life. Elucidation of the etiology and pathogenesis could offer an effective
      treatment for osteoporosis.

PMID- 8992888
TI  - Preventing pressure sores in elderly patients: a comparison of seven mattress
      overlays.

PMID- 8992890
TI  - P mitrale-P pulmonale variation.

PMID- 8992889
TI  - [Comparative study of 3 types of lancets for performing prick tests].
AB  - Skin Prick Test is considered the cutaneous test of choice in rutinary clinical
      practice as well as in research. In the last 15 years a large number of lancets
      for puncture test have been developed looking for a higher level of
      standardisation and reproducibility. We have compared three lancets, two of them,
      NeoAbello (NA) and Dome/Hollister Stier (DHS), used in puncture test and a third
      one, Blood Lancet (BL), in the modified prick test. Twenty-two patients
      sensitised to Phleum pratense were tested with the three lancets at three extract
      concentrations and histamine 10 mg/mL in duplicate. We compared their wheal sizes
      by means of parallel line assay, their reproducibility, frequency of bleeding
      wheals, the disturbance for the patient and the correlation between specific IgE
      and skin response. Wheal size was similar for puncture tests (DHS and NA lancets)
      and significatively lower than BL, being necessary to increase 1.9 times the
      extract concentration when using DHS and NA lancets to achieve the same wheal
      size than when using BL lancets (p < 0.01). Reproducibility with histamine was
      similar with the three lancets while with the extract was somehow better with
      puncture tests but without statistical significance. Bleeding was significantly
      more frequent with BL although this did not influence the results. Less pain was
      obtained with BL. Finally, correlation with specific IgE was slightly significant
      for NA and very similar for the other two. With these results in mind we think
      that any of the three lancets is valid for the diagnostic of the allergic
      patient. Nevertheless, puncture tests are probably the most suitable at a
      research level.

PMID- 8992891
TI  - [ENT emergencies due to foreign bodies at a tertiary hospital].
AB  - A study of the patients who, through a year, came to the Emergencies Department
      showing foreign bodies in ENT-area has been accomplished. Among ENT urgencies
      foreign bodies constitute the most frequent cases. Age, sex, date, time of
      admission, sitting, kind of body and treatment are taken in consideration. The
      intruders were most commonly found in the pharyngeal area. A striking
      correspondence between age and location is underlined.

PMID- 8992892
TI  - [Tracheocele: a case report].
AB  - Report of one tracheocele case casually uncovered in a man 51-year-old. Starting
      from the difference between congenital and acquired cases of this pathology the
      AA. refer to the symptomatologic picture, to diagnostical and therapeutical
      measures as well, pinpointing to possible complications that may arise specially
      by infants during the lactation period.

PMID- 8992893
TI  - [Vertical partial laryngectomies: our experience].
AB  - This paper deals with a retrospective analysis of 162 patients with glottic
      cancer treated in our ENT-Department using vertical partial laryngectomies
      (cordectomy and partial surgery with cartilage resection. PSCR). The term of
      study comprise from 1975 till 1991. In this interval were performed 118
      cordectomies and 44 partial laryngectomies including cartilage resection. The
      parameters considered were: clinical onset, tumor sitting, TNM and pTNM
      classification, histopathological findings and treatment and survival and
      recurrence rates at 5 years, as well.

PMID- 8992894
TI  - [Assessment of nasal mucociliary transport time in seasonal allergic rhinitis].
AB  - The AA. study the mucociliary transport time resorting to the vegetable coal dust
      method, in 64 individuals suffering seasonal allergic rhinitis, during the
      pollinosis epoch (1991-1992). This collective was divided in two groups according
      to the presence of hidrorrhea at examination: those subjects in whom the disease
      was considered in activity or inactive. The results were compared with those
      resulting from a group of other 130 healthy people. The conclusion drawn out is
      that the full high moment of the seasonal allergic rhinitis influences the
      cessation or the cancellation of the mucociliary function. The halt of the
      rhinohidrorrhea clearly improves the mucociliary clearance but without attaining
      its normalization during the pollinosis epoch.

PMID- 8992896
TI  - [Meningioma with otological etiology].
AB  - Meningiomas are tumours which first symptomatology are related to its sitting.
      When localized in the posterior fossa present as otological complaints and may
      mimic other otological conditions. The AA. report 3 meningioma cases starting
      with audiovestibular pictures. All were both electrophysiologically and
      radioimaging studied and underwent an otoneurologic procedure and the
      histopathological verification. The paper underlines the importance of these
      cases for ENT-specialist under both the clinical and surgical point of view.

PMID- 8992895
TI  - [On adenoidectomy].
AB  - The paper deals on the advantages for the rhinopharynx following adenoidectomy.
      The AA. explain their procedure for its removal under visual control. Both a
      radiological and microbiological study was done in 90 children waiting for the
      removal with the aim of realizing the changes derived to the upper air-way. The
      surgery enhances the adenoidal expression and significatively improves the
      rhinopharyngeal air-way (p < 0.001). Furthermore the pathogenic flora of
      epipharynx changes for benefit of the saprophytic flora (p < 0.001). The
      adenoidectomy is indicated when the adenoidal mass hinder the nasopharyngeal
      breathing, when causes adenoid outbreaks and also in those cases of stubborn
      secretory otitis not yielding to conservative treatment.

PMID- 8992897
TI  - [Laryngeal amyloidosis and multiple myeloma: a case report].
AB  - The AA. report the case of a 68-year-old man, treated in their ENT-Department,
      presenting with amyloid accumulations in the larynx in the context of systemic
      amyloidosis associated to a multiple myeloma. Review of diagnostic methods in
      order to identify the lesion and the general malady as well. Approach to the
      adequate treatment.

PMID- 8992898
TI  - [Tumoral collision: cancer metastases within a second neoplasm].
AB  - A case report of epithelial carcinoma of the inferior lip which spread in
      cervical lymph nodes previously affected by a chronic lymphocitic leukaemia, is
      presented. The coexistence of both histological findings in some of the nodes
      (collision tumor) is remarked. We have made a review of the scanty literature
      about metastases on second tumors and compared and commented those features.

PMID- 8992899
TI  - [Primary mucous melanoma of the nasal cavity: a case report].
AB  - Mucous melanoma in the nasal cavity are unusual tumours that develop from common
      melanocytes pre-existent in the respiratory epithelium. They manifest a high
      diagnostic and therapeutic difficulties as well as an obscure prognosis. A case
      of this rare tumour is exposed and a bibliographic review in which clinical,
      diagnostic, histological, therapeutic and prognostic features are contemplated.

PMID- 8992900
TI  - [Hospital register for upper aerodigestive tract malignancies in health care in
      Zamora. A discriptive study].
AB  - Incidence of malignant tumours of the upper digestive tract and airway (naso
      endooropharynx, hypopharynx, larynx, oral cavity, salivary glands and neck
      tumours of unknown origin) from 1992 to 1994 in Zamora's Sanitary Area (Virgen de
      la Concha Hospital) is evaluated. Geographic distribution according to the
      residence, tumour sitting, age and staging of the growth is exposed. The
      incidence is estimated at 24.7 cases per 100.000 inhabitants and year (lymphomas
      excluded). Utility of the cancer register for clinic activity and epidemiological
      research is stressed.

PMID- 8992901
TI  - [Thoughts on the 150th anniversary of anesthesia].

PMID- 8992902
TI  - [Prehospital fluid resuscitation].
AB  - Trauma and associated major blood losses in Germany represent the leading cause
      of mortality in patients up to 45 years of age. The endpoints of prehospital
      fluid resuscitation in traumatic-hemorrhagic shock are the restitution of
      intravascular volume und cardiac preload, in order to increase cardiac output and
      thus provide adequate oxygen delivery to the tissues. The key therapeutic factor
      to prevent the development of multiple organ failure complicating trauma and
      shock, however, is the normalization not only of macrohemodynamics (systemic
      blood pressure. cardiac output), but the restitution of the disturbed
      microvascular perfusion. In case of major blood loss and exsanguination this can
      not be achieved by crystalloids and synthetic colloids used in conventional
      volume therapy. A new concept consists of i.v. bolus infusion of a small volume
      (4 ml/kg body weight) of a hyperosmolar (7.2-7.5%) NaCl/colloid solution, which
      is termed "Small-volume Resuscitation". Recently presented data from a cohort
      analysis of 8 preclinical studies show an increase in survival rate by about 5%
      when compared to standard of care. In addition, artificial oxygen carrying
      solutions are currently investigated. by which-through an increase of O2-blood
      content-oxygen delivery to the tissues might be augmented.

PMID- 8992903
TI  - [The effects of cimetidine on the pharmacodynamics of rocuronium].
AB  - Cimetidine is a commonly used H2-receptor antagonist that has been recommended
      for the prevention of acid aspiration syndrome and has been shown to potentiate
      vecuronium-induced neuromuscular block. The present study was designed to
      investigate the influence of a single IV dose of cimetidine on the neuromuscular
      effects of rocuronium, an analogue of vecuronium with a short onset time.
      METHODS: Twenty adults aged 18-65 years were included in the study with their
      informed consent and approval of the Ethics Committee. Following oxazepam
      premedication, 10 patients were randomly allocated to receive cimetidine 400 mg
      IV 30 min before anaesthesia. After fentanyl and thiopentone induction, single
      twitch stimulation of the ulnar nerve was performed every 10 s. Following
      stabilisation of control responses, patients received rocuronium 0.6 mg/kg for
      intubation. Anaesthesia was maintained with enflurane < or = 0.8 vol.% (end
      tidal) and 65% nitrous oxide. Onset time and recovery times to 25% and 75% of the
      twitch control values were recorded. RESULTS: Onset and recovery times did not
      differ between groups. CONCLUSIONS: The results of the present study demonstrate
      that cimetidine does not increase the duration of rocuronium neuromuscular
      blockade. Inhibition of the cytochrome P450 system or a direct effect at the
      neuromuscular junction have been suggested as the mechanisms of drug interaction
      associated with cimetidine. Impairment of hepatic microsomal drug metabolism
      results in a prolonged duration of action of vecuronium, which appears to be
      eliminated primarily via the liver. Data on the elimination pathway of rocuronium
      in humans are not available. The fact that cimetidine does not alter the recovery
      from rocuronium-induced neuromuscular block confirms a previous suggestion that
      rocuronium may not be eliminated principally by the liver. A direct effect of
      cimetidine on the neuromuscular junction could not be confirmed by this study.
      Therefore, cimetidine can be given as premedication without a risk of prolonged
      rocuronium block.

PMID- 8992904
TI  - [The effects of age on onset and recovery from atracurium, rocuronium and
      vecuronium blockade].
AB  - Elderly patients may show an age-related decline in physiologic functions, which
      may be responsible for the prolonged duration of some neuromuscular blocking
      agents. Previous studies have yielded conflicting results as to the effects of
      these drugs in the elderly. METHODS: After obtaining informed consent and
      approval of the Ethics Committee, we compared onset and recovery times of single
      IV doses of atracurium, rocuronium, and vecuronium given to 108 patients divided
      into three groups according to age (18-50, 51-64, > or = 65 years). Following
      oxazepam premedication and fentanyl and thiopentone induction, patients were
      randomly allocated to receive atracurium, rocuronium or vecuronium (0.5, 0.6, or
      0.1 mg/kg, respectively) in < or = 0.8 vol.% enflurane (end-tidal)-nitrous oxide
      anaesthesia. Muscular relaxation was assessed by electromyographic (EMG)
      recording of the adductor pollicis muscle after supramaximal single-twitch
      stimulation of the ulnar nerve every 10 s. Onset time and recovery to 25%, 75%
      and 90% of twitch control values (DUR25, 75, 90) were recorded. Creatinine
      clearance predicted from serum creatinine (Ccr) was correlated with recovery from
      neuromuscular block. RESULTS: Onset time was not different among groups or
      relaxants. The results showed a prolonged duration of action for atracurium
      (DUR75, DUR90), rocuronium (DUR25, DUR75), and vecuronium (DUR25) in the elderly.
      A number of patients did not reach DUR75 or DUR90. There was a significant
      relationship between age and failure to return to control values during recovery
      from neuromuscular block, especially after atracurium and rocuronium. Ccr showed
      a negative correlation with age for all relaxants, but a negative significant
      correlation between Ccr and recovery was found only for rocuronium. CONCLUSIONS:
      This study suggests that onset time for atracurium, rocuronium and vecuronium is
      not age-dependent. Recovery was prolonged in the elderly for all three relaxants.
      This effect appears to be secondary to changes in body composition and function
      accompanying the aging process. Neither atracurium nor vecuronium depends
      significantly on the kidney for elimination, but the negative correlation between
      Ccr and rocuronium suggests an appreciable role for the kidney in the elimination
      of this relaxant. The long recovery times observed in this study could also be
      related to enflurane anaesthesia. We suggest that failure of EMG responses to
      return to baseline values during recovery from neuromuscular block may be related
      to age, especially for atracurium and rocuronium.

PMID- 8992905
TI  - [Movement of the temporomandibular joint during tracheal intubation].
AB  - Laryngoscopy causes temporary postoperative dysfunction of the temporomandibular
      joint (TMJ): during iatrogenic TMJ manipulation in anaesthetised patients, the
      TMJs have lost the protection afforded by the tone of the surrounding muscles.
      Thus far, the exact type and extent of TMJ movements have not been known. The
      purpose of this study was to develop a method to visualise and assess TMJ
      movements during intubation by means of electronic axiography, a diagnostic
      monitor of TMJ movements used in dentistry: registration of the hinge axis (HA)
      as an equivalent of the condylar paths on extra-oral sagittaly mounted, parallel
      plates. The HA is individually defined in each patient by the pure, rotating TMJ
      movement during initial mouth opening (no farward gliding of the condyles,
      incisor distance up to 10 mm). The parallel plates are placed in the TMJ region
      in the skull-mounted plate bow: both registration tips ("drawing" the HA tracings
      on the electronic plates) are connected to the mandible by a face bow,
      paraocclusally fixed to the teeth. The face bow is individually shaped for each
      patient to allow mask ventilation and free movement of the laryngoscope during
      intubation. HA tracings are registered and calculated for both sides
      independently every 24 ms with the SAM/Klett system and presented on sagittal and
      frontal projections. In the operating theatre, the active mouth-opening traces
      (MOT) are registered first and the passive endotracheal intubation traces (EIT)
      after induction of anaesthesia (same head position). With informed consent and
      approval by the ethics committee of the Landesarztekammer Rheinland Pfalz. 40
      male patients (ASA I. Mallampati I, limb surgery) were randomly allocated to four
      groups (n = 10 each). OS: Oral intubation, suxamethonium (1.5 mg/ kg); OV: Oral
      intubation, vecuronium (0.1 mg/kg); NS: Nasal intubation, suxamethonium (1.5
      mg/kg); and NV: Nasal intubation, vecuronium (0.1 mg/kg). Intubation was
      performed 100 s after injection of the relaxant. Pre- and postoperatively (every
      24 h over 3 days, in case of positive findings longer) recorded were: active
      movements of the mandible (maximal mouth opening/ max. laterotrusion);
      dysfunction of the TMJ; and pain sensation in the TMJ (Helkimo rating). MOTs and
      EITs were recorded and analysed with the system described and typical EIT
      patterns were identified: bland, clinically uneventful intubations (n = 7),
      massive distraction and laterotrusion of the EIT compared to the MOT (n = 24),
      and blocked or limited TMJ movements resulting in intubation problems (n = 1).
      With the method presented, TMJ movements could be visualised during endotracheal
      intubation for the first time. It can be used to assess techniques, routes, and
      instruments for intubation as well as to evaluate potential traumatising
      movements during endotracheal intubation.

PMID- 8992907
TI  - [Anesthesia in endovascular treatment of aortic aneurysm. Results and
      perioperative risks].
AB  - Surgical treatment of aortic aneurysms carries significant cardiovascular risks.
      Transvascular insertion of endoluminal prostheses is a new, minimally invasive
      treatment for aortic aneurysms. The pathophysiology of this novel procedure,
      risks and benefits of different anaesthetic techniques, and typical complications
      need to be defined. METHODS: With their informed, written consent, 19 male
      patients aged 48-83 years of ASA physical status III and IV with infrarenal (n =
      18) or thoracic (n = 1) aortic aneurysms underwent 23 stenting procedures under
      general endotracheal (n = 9), epidural (n = 8), or local anaesthesia with
      sedation (n = 6). Intra-anaesthetic haemodynamics, indicators of postoperative
      (p.o.) oxygenation and systemic inflammatory response, and perioperative
      complications were analysed retrospectively and compared between anaesthetic
      regimens. RESULTS: Groups were well matched with regard to morphometry and
      preoperative risk profiles (Table I). The use of pulmonary artery pressure
      monitoring, incidence of intraoperative hypotensive episodes, and p.o. intensive
      care was more frequent with general anaesthesia. Groups did not differ in total
      duration of anaesthesia care, incidence and duration of intraoperative
      hypertensive, brady-, or tachycardic periods, incidence of arterial oxygen
      desaturation, use of vasopressors, colloid volume replacements, or
      antihypertensives (Table 2). Postoperatively, all groups showed a similar,
      significant systemic inflammatory response, i.e., rapidly spiking temperature
      (p.o. evening: mean peak 38.5 +/- 1.0 degrees C). leucocytosis, and rise of acute
      phase proteins without bacteraernia (Table 3). During this period, despite
      supplemental oxygen, pulse oximetry revealed temporary arterial desaturation in
      13 of 18 patients (70%) (Table 3). In 3 patients, hyperpyrexia was associated
      with intermittent tachyarrhythmias (n = 3) and angina pectoris (n = 1). There was
      no conversion to open aortic surgery, perioperative myocardial infarction, or
      death. CONCLUSIONS: Regional and local anaesthesia with sedation are feasible
      alternatives to general endotracheal anaesthesia for minimally invasive treatment
      of aortic aneurysms by endovascular stenting. However, invasive monitoring and
      close postoperative monitoring are strongly recommended with either method.
      Specific perioperative risks in patients with limited cardiovascular or pulmonary
      reserve are introduced by the abacterial systemic inflammatory response to aortic
      stent implantation. Hyperpyrexia increases myocardial and whole-body oxygen
      consumption, and can precipitate tachyarrhythmias. Hyperfibrino-genaemia may
      increase the risk of postoperative arterial and venous thromboses. Close
      monitoring of vital parameters and prophylactic measures, including oxygen
      supplementation, low-dose anticoagulation, antipyretics, and fluid replacement
      are warranted until this syndrome resolves.

PMID- 8992906
TI  - [The transillumination technique. An alternative to conventional intubation?].
AB  - The technique of light-guided intubation is based on the principle that a source
      of light brought into the trachea results in clearly visible and defined
      transcutaneous illumination, while no illumination can be observed with the light
      source in the oesophagus (Fig. 1-7). The Trachlight is a reintroduced instrument
      for this alternative intubation technique. The essential developments are: a
      length-adjustable stylet with a removable internal metal wire, a brighter light
      source, a stable handle with tight fixation of the endotracheal tube, and a time
      dependent warning device to avoid extended intubations. One hundred twenty
      patients (Mallampati I. ASA I-III) were included in the study (conventional
      intubation [group KL, n = 60]. Trachlight intubation [group TT, n = 60]. The
      goals of the investigation were to examine the handling, application, problems,
      limitations, and possible indications of the method. The recorded parameters
      were: number of intubation attempts: course and duration of intubation;
      complications; and difficulties. In 40 patients (20 in each group) the indication
      for invasive blood pressure measurement was given due to the surgical procedure,
      and circulatory parameters were recorded at defined moments during the intubation
      course. In group KL 55 patients were intubated in the attempt, 4 on the second,
      and 1 on the third (mean duration 23.6 +/- 10.4 s, range 12-60 s). Complications
      were: unilateral intubation (3 patients), bradycardia (2), asystole (1) and soft
      tissue injury (1). Of the 60 patients in group TT. 54 were intubated
      successfully, the mean time needed being 29.9 +/- 14.8 s (range: 6-61 s). The
      remaining 6 were then intubated by the conventional method. Positive results in
      group TT included: easy handling and application, no injury to soft tissues or
      teeth, and invariably correct placement of the tube. Problems included:
      sufficient transillumination was achieved only after (entire) dimming of the
      room, insufficient control over the distal end of the tube due to an unfixed
      metal wire, unintentional switching off of the light while with-drawing the metal
      wire, difficulties in withdrawing the metal wire (too strong fixation), as well
      as disturbing effects of the warning device (blinking of the light 30 s after
      switching on). Reasons for the 6 intubation failures were introduction of the
      instrument into the oesophagus despite a supposed correct position, impossibility
      of correct placement in a patient with an extremely large goiter, and
      insufficiently clear transillumination in 3 extremely obese patients. The
      cardiovascular parameters showed no changes during laryngeal manipulation; a
      clear rise in heart rate and blood pressure was recorded, however, when the tube
      was inserted into the trachea. The cardiovascular parameters during conventional
      intubations were similar. The light-guided intubation technique can be regarded
      as a further alternative for airway management, due to the described improvement
      of the instrument. The indication for the technique is given in patients in whom
      no difficulty with intubation is expected, to avoid soft tissue damage and
      traumatising temporomandibular joint movements. Preclinical use may be limited
      due to environmental brightness. In patients with expected difficult airway
      management, fiberoptic intubation will remain the method of choice.

PMID- 8992908
TI  - [The effect of preischemic blood sugar concentration on hemodynamics and regional
      organ blood flow during and following cardiopulmonary resuscitation (CPR) in
      swine].
AB  - Blood glucose alterations prior to cerebral ischaemia are associated with poor
      neurologic outcome, possibly due to extensive lactic acidosis or energy failure.
      Cerebral effects of hyper- or hypoglycaemia during cardiopulmonary resuscitation
      (CPR) are less well known. In addition, little information is available
      concerning cardiac effects of blood glucose alterations. The aim of this study
      was to evaluate the effects of pre-cardiac-arrest hypo- or hyper-glycaemia
      compared to normoglycaemia upon haemodynamics, cerebral blood flow (CBF) and
      metabolism (CMRO2), and regional cardiac blood flow during CPR subsequent to 3
      min of cardiac and respiratory arrest and after restoration of spontaneous
      circulation. METHODS: After approval by the State Animal Investigation Committee,
      29 mechanically ventilated, anaesthetised pigs were instrumented for haemodynamic
      monitoring and blood flow determination by the radiolabeled microsphere
      technique. The animals were randomly assigned to one of three groups: in group 1
      (n = 9) blood glucose was not manipulated; in group II (n = 10) blood glucose was
      increased by slow infusion of 40% glucose to 319 +/- 13 mg/dl; in group III (n =
      10) blood glucose was lowered by careful titration with insulin to 34 +/- 2
      mg/dl. After 3 min of untreated ventricular fibrillation and respiratory arrest,
      CPR (chest compressor/ventilator (Thumper) and epinephrine infusion) was
      commenced and continued for 8 min. Thereafter, defibrillation was attempted, and
      if successful, the animals were observed for another 240 min. Cerebral perfusion
      pressure (CPP), CBF, CMRO2, coronary perfusion pressure (CorPP), and regional
      cardiac blood flow were determined at control, after 3 min of CPR, and at 10.30,
      and 240 min post-CPR. RESULTS: In group 1. 4/9 animals (44%) could be
      successfully resuscitated; in group II 4/10 (40%); and in group III 0/10 (0%).
      Prior to cardiac arrest, mean arterial pressure, CPP, and CorPP in group III were
      significantly lower compared to groups I and II. In group I. CPP during CPR was
      26 +/- 6 mmHg; CBF 31 +/- 9 ml/ min/100g CMRO2 3.8 +/- 1.2 ml/ min/100 g; CorPP
      18 +/- 5 mmHg; and left ventricular (LV) flow 35 +/- 15 ml/min/100 g. In group
      II; CPP = 21 +/- 5; CBF 21 +/- 7; CMRO2 1.8 +/- 0.8; CorPP 16 +/- 6; and LV flow
      22 +/- 9; and in group III: CPP 15 +/- 3; CBF 11 +/- 8; CMRO2 1.5 +/- 1.1; CorPP
      4 +/- 2; and LV flow 19 +/- 10. During the 240-min post-resuscitation period,
      there were no differences in CBF, CMRO2, or LV flow between groups I and II.
      CONCLUSION: Hypoglycaemia prior to cardiac arrest appears to be predictive for a
      poor cardiac outcome, whereas hyperglycaemia does not impair resuscitability
      compared to normoglycaemia. In addition, hyperglycaemia did not affect LV flow,
      CBF, or CMRO2. However, it has to be kept in mind that haemodynamics and organ
      blood flow do not permit conclusions with respect to functional neurologic
      recovery or histopathologic damage to the brain, which is very likely to be
      associated with hyperglycaemia.

PMID- 8992909
TI  - [Adaptive lung ventilation (AVL). Evaluation of new closed loop regulated
      respiration algorithm for operation in the hyperextended lateral position].
AB  - The lateral decubitus position is the standard position for nephrectomies. There
      is a lack of data about the effects of this extreme position upon respiratory
      mechanics and gas exchange. In 20 patients undergoing surgery in the nephrectomy
      position, we compared a new closed-loop-controlled ventilation algorithm,
      adaptive lung ventilation (ALV), which adapts the breathing pattern
      automatically, to the respiratory mechanics with conventionally controlled
      mandatory ventilation (CMV). The aims of our study were (1) to describe
      positioning effects on respiratory mechanics and gas exchange, (2) to compare
      ventilatory parameters selected by the ALV controller with traditional settings
      of CMV, and (3) to assess the individual adaptation of the ventilatory parameters
      by the ALV controller. The respirator used was a modified Amadeus ventilator,
      which is controlled by an external computer and possesses an integrated lung
      function analyzer. In a first set of measurements, we compared parameters of
      respiratory mechanics and gas exchange in the horizontal supine position and 20
      min after changing to the nephrectomy position. In a second set of measurements,
      patients were ventilated with ALV and CMV using a randomized crossover design.
      The CMV settings were a tidal volume of 10 ml/kg body weight, a respiratory rate
      of 10 breaths/min, an I:E ratio of 1:1.5, and an end-inspiratory pause of 30% of
      inspiratory time. With both ventilation modes F1O2 was set to 0.5 and PEEP to 3
      cm H2O. During ALV a desired alveolar ventilation of 70 ml/ kg KG.min was preset.
      All other ventilatory parameters were determined by the ALV controller according
      to the instantaneously measured respiratory parameters. Positioning induced a
      reduction of compliance from 61.6 to 47.9 ml/cm H2O; the respiratory time
      constant shortened from 1.2 to 1.08 s, whereas physiological dead space increased
      from 158.9 to 207.5 ml. On average, the ventilatory parameters selected by the
      ALV controller resembled very closely those used with CMV. However, an adaptation
      to individual respiratory mechanics was clearly evident with ALV. In conclusion,
      we found that the effects of positioning for nephrectomy are minor and may give
      rise to problems only in patients with restrictive lung disease. The novel ALV
      controller automatically selects ventilatory parameters that are clinically sound
      and are better adapted to the respiratory mechanics of ventilated patients than
      the standardized settings of CMV are.

PMID- 8992910
TI  - [Accuracy of measurement and overestimation of CO2 of two capnometers intended
      for potential use in emergency medicine].
AB  - Capnometry, the noninvasive measurement of end-expiratory CO2 concentration
      (cCO2, vol%) or calculation of its respective partial pressure (pCO2; mmHg) is an
      established method. However, for prehospital settings, capnometry is still used
      very restrictively, mainly owing to the respective devices used. The prerequisite
      for their use is sufficient accuracy (+/-2 mmHg) and easy handling. Two special
      capnometers (STAT CAP. Nellcor: mainstream, semiquantitative estimation;
      Capnocheck 8200, BCI: sidestream, quantitative measurement, numeric display),
      developed recently for potential use in emergency medicine, are said to fit these
      criteria. Therefore, the objective of the present investigation was to assess the
      accuracy and precision of both devices, comparing methods under standardized in
      vitro (reference gases) and in vivo (intubated and ventilated patients)
      conditions. METHODS: Both devices ("STAT CAP": pCO2 range, light bars;
      "Capnocheck 8200") were evaluated regarding the accuracy of pCO2 (Capnocheck) and
      the precision of the CO2 range (STAT CAP). Tests were performed with four dry gas
      mixtures (STPD) of defined composition and during ventilation of 20 intubated
      patients (BTPS). All measurements were compared with the alveolar gas monitor
      "AGM 1304" (Bruel & Kjaer, Denmark) as a reference method with a proven +/- 1
      mmHg accuracy of pCO2 measurement. RESULTS: The "Capnocheck" (BCI) presented an
      accuracy of the pregiven pCO2 of 0.7-1.4 mmHg (dry gas mixtures, STPD) and an
      overestimation of 0.2 +/- 4.1 mmHg (BTPS) during ventilation with pure oxygen;
      inaccuracy during ventilation with 70% N2O in O2 proved to be + 1.2 +/- 1.7 mmHg
      (BTPS). Nellcor's "STAT CAP" failed to reach the target value in 10% of analyses,
      as shown by the respective segment bar of the display. CONCLUSION: Evaluation of
      the accuracy of capnometers must focus on the necessary pH2O correction and the
      possible effects exercised by O2 (and N2O) as well as the possible dependence on
      barometric pressure (if pCO2, mmHg, is the desired value). The "Capnocheck"
      showed an accuracy of more than 2 mmHg in dry gas mixtures as well as in
      humidified air. Concerning the practical use during constant artificial
      ventilation, the digital display and accuracy of the sidestream capnometer allow
      for reliable conclusions on patients' ventilation and circulation (CO2
      elimination). The 90% accuracy of the segment bar display of Nellcor's "STAT
      CAP", per se covering only a rather broad range of 20 mmHg, obviously does not
      provide more than a rough overview. Therefore, the STAT CAP cannot be recommended
      for prehospital capnometry in the field. However, both the accuracy of the BCI
      capnometer (Capnocheck) and its numeric display and easy handling strongly
      recommend this device also for clinical use.

PMID- 8992911
TI  - [Hypnosis--a side effect-free alternative to medical sedation in regional
      anesthesia].
AB  - Hypnosis can be an alternative to cerebral sedatives with no side effects for
      sedation during regional anaesthesia, especially in high-risk and fearful
      patients. Patients who have experience with relating techniques like Jakobson's
      progressive muscle relaxation are very good candidates for hypnosis. It is
      contraindicated in patients with psychotic disorders, major depression, and abuse
      of hallucinogenic drugs. The authors shows his personal method of hypnosis based
      on fixation and suggestive techniques like muscle relaxation, temperature
      sensation, and creation of emotional pictures. Of ten cases, hypnosis was
      successful in six (vegetative stress symptoms like tachycardia or shivering
      stopped immediately after induction of hypnosis), not completely successful in
      two (interruption of hypnosis after 30 min) and unsuccessful in two. Four cases
      where hypnosis was used during spinal anaesthesia for knee and hip surgery or
      brachial plexus block for open fixation of Colles' fracture are discussed as
      examples. As it requires more time (15 to 45 min to inform and test the patient)
      and special organisational conditions hypnosis will not become a routine
      procedure, but is still a good alternative for selected cases.

PMID- 8992912
TI  - ["A discovery in surgery" 150 years of anesthesia].

PMID- 8992913
TI  - [Hemorrhagic shock].

PMID- 8992914
TI  - ["Blood gas analysis" by W. Bomke, M. O. Krebs and R. Rossaint in number 3/96].

PMID- 8992915
TI  - [Use of hydroxyethyl starch in patients with renal insufficiency].

PMID- 8992916
TI  - [Optimal regional anesthesia procedure in cesarean section].

PMID- 8992917
TI  - Cost-effectiveness of implantable cardioverter defibrillators relative to
      amiodarone for prevention of sudden cardiac death.
AB  - BACKGROUND: Implantable cardioverter defibrillators (ICDs) are remarkably
      effective in terminating ventricular arrhythmias, but they are expensive and the
      extent to which they extend life is unknown. The marginal cost-effectiveness of
      ICDs relative to amiodarone has not been clearly established. OBJECTIVE: To
      compare the cost-effectiveness of a third-generation implantable ICD with that of
      empirical amiodarone treatment for preventing sudden cardiac death in patients at
      high or intermediate risk. DESIGN: A Markov model was used to evaluate health and
      economic outcomes of patients who received an ICD, amiodarone, or a sequential
      regimen that reserved ICD for patients who had an arrhythmia during amiodarone
      treatment. MEASUREMENTS: Life-years gained, quality-adjusted life-years gained,
      costs, and marginal cost-effectiveness. RESULTS: For the base-case analysis, it
      was assumed that treatment with an ICD would reduce the total mortality rate by
      20% to 40% at 1 year compared with amiodarone and that the ICD generator would be
      replaced every 4 years. In high-risk patients, if an ICD reduces total mortality
      by 20%, patients who receive an ICD live for 4.18 quality-adjusted life-years and
      have a lifetime expenditure of $88,400. Patients receiving amiodarone live for
      3.68 quality-adjusted life-years and have a lifetime expenditure of $51,000.
      Marginal cost-effectiveness of an ICD relative to amiodarone is $74,400 per
      quality-adjusted life-year saved. If an ICD reduces mortality by 40%, the cost
      effectiveness of ICD use is $37,300 per quality-adjusted life-year saved. Both
      choice of therapy (an ICD or amiodarone) and the cost-effectiveness ratio are
      sensitive to assumptions about quality of life. CONCLUSIONS: Use of an ICD will
      cost more than $50,000 per quality-adjusted life-year gained unless it reduces
      all-cause mortality by 30% or more relative to amiodarone. Current evidence does
      not definitively support or exclude a benefit of this magnitude, but ongoing
      randomized trials have sufficient statistical power to do so.

PMID- 8992918
TI  - Coronary artery bypass graft surgery in Ontario and New York State: which rate is
      right? Steering Committee of the Cardiac Care Network of Ontario.
AB  - BACKGROUND: Previous studies have shown that the rate of coronary artery bypass
      graft (CABG) surgery is much higher in New York State than in Ontario. OBJECTIVE:
      To compare the service context and clinical characteristics of patients having
      CABG surgery in New York and Ontario. DESIGN: Retrospective analysis of data from
      cardiac surgery registries in New York and Ontario. PATIENTS: All 16,690 patients
      in New York and 5517 patients in Ontario who had isolated CABG surgery in 1993.
      MEASUREMENTS: Clinical characteristics of patients having CABG surgery and rates
      of CABG surgery by coronary anatomy. RESULTS: The overall age-adjusted rate of
      isolated CABG surgery was 1.79 times (95% CI, 1.74 to 1.85) greater in New York
      than in Ontario. Patients who had CABG surgery in New York were more likely to be
      elderly and female and to have recently had myocardial infarction (P < 0.001),
      whereas patients who had CABG surgery in Ontario were more likely to have had
      left ventricular dysfunction and severe coronary artery disease (two-vessel
      disease with proximal left anterior descending disease, three-vessel disease, or
      left main disease) (P < 0.001). The relative rate of CABG surgery for left main
      disease was 2.53 times (CI, 2.35 to 2.73) greater in New York than in Ontario but
      was 8.97 times (CI, 8.01 to 10.06) greater for patients with limited coronary
      artery disease (one-vessel or two-vessel disease without proximal left anterior
      descending disease). CONCLUSIONS: The higher rates of CABG surgery in New York
      are associated with higher rates of CABG surgery among the elderly, women, and
      patients who recently had myocardial infarction. Potential underservicing in
      Ontario is suggested by a lower rate of CABG surgery for left main disease;
      however, the higher rate of CABG surgery in New York is also associated with a
      strikingly higher rate of surgery in patients with limited coronary disease. Such
      trade-offs highlight the difficulty of defining an optimal rate of CABG surgery.

PMID- 8992919
TI  - Postoperative hyponatremia despite near-isotonic saline infusion: a phenomenon of
      desalination.
AB  - BACKGROUND: It is widely presumed that the development of postoperative
      hyponatremia (which may be severe) results from administration of hypotonic
      fluids while antidiuretic hormone is acting. OBJECTIVE: To show that hyponatremia
      would occur in patients 24 hours after surgery if only near-isotonic solutions
      are given and to evaluate the mechanisms responsible for hyponatremia in this
      setting. DESIGN: Prospective cohort study. SETTING: University medical center.
      PATIENTS: 22 women who were having uncomplicated gynecologic surgery with
      infusion of near-isotonic solutions only (sodium chloride, 154 mmol/L, or Ringer
      lactate [sodium, 130 mmol/L, and potassium, 4 mmol/L]). MEASUREMENTS: Plasma
      electrolyte levels were measured at the time of induction of anesthesia and 24
      hours later. Data on the balance of water and electrolytes were obtained for the
      same 24-hours period. RESULTS: At the time of induction of anesthesia, the plasma
      sodium concentration was 140 +/- 1 mmol/L; 24 hours later, it decreased in 21 of
      22 patients (mean decrease, 4.2 +/- 0.4 mmol/L [P < 0.001]; lowest level, 131
      mmol/L in 2 patients). The urine remained hypertonic (peak sodium plus potassium
      concentration in urine, 294 +/- 9 mmol/L) in all patients for the first 16 hours
      after induction of anesthesia. CONCLUSIONS: Postoperative hyponatremia occurred
      within 24 hours of induction of anesthesia when only near-isotonic fluids were
      infused. Hyponatremia was generally caused by generation of electrolyte-free
      water during excretion of hypertonic urine-a desalination process. This
      electrolyte-free water was retained in the body because of the actions of
      antidiuretic hormone. If the pathophysiology of this hyponatremic state is
      understood, recommendations for its prevention and treatment can be deduced.

PMID- 8992920
TI  - Relation between plasma leptin levels and measures of body fat in identical twins
      discordant for obesity.
AB  - BACKGROUND: Plasma levels of leptin, the recently discovered satiety hormone, are
      associated with adiposity in humans. OBJECTIVE: To determine whether genetic
      factors or body fat distribution affect the association between leptin levels and
      obesity. PARTICIPANTS: 23 healthy identical twin pairs (9 male pairs and 14
      female pairs, 33 to 59 years of age) who were discordant for obesity (average
      weight difference, 18 kg). MEASUREMENTS: Fasting plasma leptin levels were
      measured by radioimmunoassay. Distribution of abdominal fat into visceral and
      subcutaneous compartments was estimated by use of magnetic resonance imaging.
      RESULTS: Plasma leptin levels were threefold higher in obese twins than in lean
      twins (mean +/- SD, 18.7 +/- 12.5 micrograms/L compared with 6.4 +/- 4.8
      micrograms/L; P < 0.001); a similar difference was seen when the entire study
      group was divided according to sex. Compared with lean twins, plasma leptin
      levels were 3.7-fold higher in the obese twins who had visceral fat accumulation
      greater than the median and 2.1-fold higher in the obese twins who had visceral
      fat accumulation less than the median. The intrapair differences in leptin levels
      correlated with the corresponding differences in percentage of body fat in women
      (r = 0.73; P = 0.003) but not in men and correlated with differences in visceral
      fat area in men (r = 0.79; P = 0.019) and women (r = 0.73; P = 0.007). In
      multiple regression analyses that included intrapair differences in visceral fat
      area and total body fat, the association between differences in visceral fat area
      and leptin levels was significant in men (P = 0.029) but not in women.
      CONCLUSIONS: Plasma leptin levels are increased in obese persons, independent of
      genetic background. Visceral fat may be of special importance in the regulation
      of leptin levels, but it is probably less important in women than in men.

PMID- 8992922
TI  - Uniform requirements for manuscripts submitted to biomedical journals.
      International Committee of Medical Journal Editors.

PMID- 8992921
TI  - Association between polycystic ovaries and extent of coronary artery disease in
      women having cardiac catheterization.
AB  - BACKGROUND: Women with polycystic ovaries have associated risk factors for
      coronary artery disease. It is unknown whether women with more extensive coronary
      artery disease are more likely to have polycystic ovaries. OBJECTIVE: To
      determine whether women who have more extensive coronary artery disease as seen
      on coronary angiography are more likely to have polycystic ovaries appearing on
      ultrasonography than are women with less severe coronary disease. DESIGN:
      Prevalence study of women who had had coronary angiography. SETTING: Women
      referred for coronary angiography for assessment of chest pain or valvular
      disease in Auckland, New Zealand, during a 2-year period. PATIENTS: 143 women 60
      years of age or younger who had had coronary angiography. Women who had
      previously had bilateral oophorectomy were excluded. MEASUREMENTS: The extent of
      coronary artery disease assessed by quantitative angiography was compared with
      the presence or absence of polycystic ovaries. Pelvic ultrasonography was done
      without knowledge of the extent of coronary artery disease. Assessment of
      angiograms was blinded. Insulin resistance and gonadotropin, testosterone, and
      serum lipid levels were also measured. RESULTS: Polycystic ovaries were found in
      42% of women and were associated with hirsutism; previous hysterectomy; higher
      free testosterone, triglyceride, and C-peptide levels; and lower high-density
      lipoprotein cholesterol levels. Women with polycystic ovaries had more extensive
      coronary artery disease than women with normal ovaries (number of segments with >
      50% stenosis, 1.7 [95% CI, 1.1 to 2.3] compared with 0.82 [CI, 0.54 to 1.1]; P <
      0.01). On logistic regression analysis, the extent of coronary artery disease (P
      = 0.032) and family history of heart disease (P = 0.022) were predictors of the
      presence of polycystic ovaries. CONCLUSIONS: In women having coronary
      angiography, those with more extensive coronary artery disease were more likely
      to have polycystic ovaries on ultrasonography than were those with less extensive
      disease. Visualization of polycystic ovaries by sonography was associated with
      distinct metabolic and endocrine abnormalities. Further study is required to
      evaluate whether surgery or hormone replacement therapy can modify the risk.

PMID- 8992923
TI  - Update in infectious diseases.

PMID- 8992924
TI  - Myelinolysis after correction of hyponatremia.
AB  - Myelinolysis is a neurologic disorder that can occur after rapid correction of
      hyponatremia. Initially named "central pontine myelinolysis," this disease is now
      known to also affect extrapontine brain areas. Manifestations of myelinolysis
      usually evolve several days after correction of hyponatremia. Typical features
      are disorders of upper motor neurons, spastic quadriparesis and pseudobulbar
      palsy, and mental disorders ranging from mild confusion to coma. Death may occur.
      The motor and localizing signs of myelinolysis differ from the generalized
      encephalopathy that is caused by untreated hyponatremia. Experiments have
      duplicated the clinical and pathologic features of myelinolysis by rapidly
      reversing hyponatremia in animals. Myelinolysis is more likely to occur after the
      treatment of chronic rather than acute hyponatremia and is more likely to occur
      with a rapid rate of correction. The exact pathogenesis of myelinolysis has not
      been determined. Optimal management of hyponatremic patients involves weighing
      the risk for illness and death from untreated hyponatremia against the risk for
      myelinolysis due to correction of hyponatremia. Experiments in animals and
      clinical experience suggest that correction of chronic hyponatremia should be
      kept at a rate less than 10 mmol/L in any 24-hour period.

PMID- 8992925
TI  - Effects of amiodarone on thyroid function.
AB  - PURPOSE: To review the literature on the effects of amiodarone on thyroid
      physiology and management of amiodarone-induced thyroid disease. DATA SOURCES:
      English-language articles identified through a MEDLINE search (for 1975 to 1995,
      using the terms amiodarone and thyroid) and selected cross-referenced articles.
      STUDY SELECTION: Articles on the effects of amiodarone on thyroid physiology and
      function tests and occurrence, recognition, and management of amiodarone-induced
      thyroid disease. DATA EXTRACTION: Data were manually extracted from selected
      studies and reports; emphasis was placed on information relevant to the
      practicing clinician. DATA SYNTHESIS: Amiodarone can have many effects on thyroid
      function test results, even in the absence of hyperthyroidism or hypothyroidism.
      It may cause an increase in serum levels of thyroxine, reverse triiodothyronine,
      and thyroid-stimulating hormone and a decrease in serum triiodothyronine levels.
      Thyrotoxicosis occurs in some patients and is related to several pathogenetic
      mechanisms. It often present dramatically with obvious clinical manifestations
      and further changes in thyroid function test results. Medical options include
      therapy with thionamides, perchlorate, and prednisone. Radioactive iodine is of
      little use. Thyroidectomy is effective and is the only measure that consistently
      allows continued use of amiodarone. Unlike thyrotoxicosis, hypothyroidism is
      related to a persistent Wolff-Chaikoff effect and often has a vague presentation.
      The goal of treatment of amiodarone-induced hypothyroidism is to bring serum
      thyroxine levels to the upper end of the normal range, as often seen in euthyroid
      patients who are receiving amiodarone. CONCLUSIONS: Thyroid dysfunction commonly
      occurs with amiodarone therapy. It may be difficult to recognize the dysfunction
      because of the many changes in thyroid function test results that occur in
      euthyroid patients who are receiving amiodarone. Effective strategies exist for
      the management of hyperthyroidism and hypothyroidism; these should be tailored to
      the needs of the individual patient.

PMID- 8992927
TI  - CONSORT: an important step toward evidence-based health care. Consolidated
      Standards of Reporting Trials.

PMID- 8992926
TI  - Recognizing bedside rationing: clear cases and tough calls.
AB  - Under increasing pressure to contain medical costs, physicians find themselves
      wondering whether it is ever proper to ration health care at the bedside. Opinion
      about this is divided, but one thing is clear; Whether physicians should ration
      at the bedside or not, they ought to be able to recognize when they are doing so.
      This paper describes three conditions that must be met for a physician's action
      to quality as bedside rationing. The physician must 1) withhold, withdraw, or
      fail to recommend a service that, in the physician's best clinical judgment, is
      in the patient's best medical interests; 2) act primarily to promote the
      financial interests of someone other than the patient (including an organization,
      society at large, and the physician himself or herself); and 3) have control over
      the use of the beneficial service. This paper presents a series of cases that
      illustrate and elaborate on the importance of these three conditions. Physicians
      can use these conditions to identify instances of bedside rationing; leaders of
      the medical profession, ethicists, and policymakers can use them as a starting
      point for discussions about when, if ever, physicians should ration at the
      bedside.

PMID- 8992928
TI  - Trial by self-assessment.

PMID- 8992929
TI  - Cyclophosphamide-induced bladder cancer.

PMID- 8992930
TI  - Increased viral load and suicidal ideation in an HIV-infected patient.

PMID- 8992931
TI  - Polycythemia vera in acromegaly.

PMID- 8992932
TI  - Effect of ethinyl estradiol on chronic active hepatitis.

PMID- 8992933
TI  - Pancreatitis, hyperlipidemia, and pregnancy in two sisters.

PMID- 8992934
TI  - Elevated serum amylase levels after seizures.

PMID- 8992935
TI  - Protein S, von Willebrand factor, and euglobulin lysis time as markers of
      coronary heart disease.

PMID- 8992936
TI  - Physicians' attitudes about patients in the persistent vegetative state.

PMID- 8992937
TI  - Physicians' attitudes about patients in the persistent vegetative state.

PMID- 8992938
TI  - "Sensitivity" and "specificity" reconsidered: the meaning of these terms in
      analytical and diagnostic settings.
AB  - Imprecise usage of the terms "sensitivity" and "specificity" produces confusion
      in the diagnostic use of sophisticated laboratory test results. "Analytical
      sensitivity" represents the smallest amount of substance in a sample that can
      accurately be measured by an assay. "Analytical specificity" refers to the
      ability of an assay to measure on particular organism or substance, rather than
      others, in a sample. An assay's analytical sensitivity and analytical specificity
      are distinct from that assay's clinical diagnostic sensitivity and diagnostic
      specificity. "Diagnostic sensitivity" is the percentage of persons who have a
      given disorder who are identified by the assay as positive for the disorder. High
      analytical sensitivity does not guarantee acceptable diagnostic sensitivity.
      "Diagnostic specificity" is the percentage of persons who do not have a given
      condition who are identified by the assay as negative for the condition. False
      positive reactions occur because of sample contamination and diminish the
      diagnostic specificity of the assay. The terms "sensitivity" and "specificity"
      should be used with the requisite adjectives because the "diagnostic" and the
      "analytical" meanings of these terms are very different.

PMID- 8992939
TI  - Randomized trial of aspirin versus aspirin and heparin in pregnant women with the
      antiphospholipid syndrome.

PMID- 8992940
TI  - Proceedings of the 13th International Enzyme Engineering Conference. San Diego,
      California, October 15-20, 1995.

PMID- 8992941
TI  - Purification of urokinase by affinity cross-flow filtration using a water-soluble
      macroligand.

PMID- 8992943
TI  - Microbial D-amino acid oxidases (EC .4.3.3).

PMID- 8992942
TI  - Application of microbial enzymes in diagnostic analysis.

PMID- 8992944
TI  - Production and stabilization of pure maltose phosphorylase from Lactobacillus
      brevis for sensing inorganic phosphate.

PMID- 8992945
TI  - Lipase-catalyzed selective esterification of ibuprofen.

PMID- 8992946
TI  - The Abdominal Aorta Aneurysm: Genetics, Pathophysiology, and Molecular Biology.
      Proceedings of a conference. New York City, March 79, 1996.

PMID- 8992947
TI  - [Genetic studies in Banat, Romania].
AB  - The genetic change in small populations which immigrated into Rumania have been
      considered with selected examples from three populations: Carasova, Lindenfeld
      and Sumita, all of which have settled down in the geographical area of Banat and
      have remained cultural isolates over hundreds of years in their new territory.
      The population of Carasova is of Serbo-Croatian origin (Kosovo and North-Albania)
      and immigrated into Rumania in the 14th century. The village of Lindenfeld was
      populated by groups of German descent who came from Bohemia after 1830. But,
      Sumita is inhabited by Czech groups of Bohemian origin which arrived in the Banat
      around the same period. The present paper compares these relatively small,
      cultural isolates with Cornereva, an area of an old Rumanian stock as well as
      with ethnohistorically or geographically related peoples. Allele frequencies of 7
      genetic marker systems (AB0, MN, RH, P, KM, HPA, TF) were used for the
      calculation of the genetic similarity and distance between these Rumanian
      isolates and related peoples. High genetic similarity is encountered between
      Lindenfeld and Sumita which is, apparently, due to their common Bohemian origin.
      Both of these populations and that of Carasova show a relatively low genetic
      similarity with Cornereva, the former endemic Rumanian population. These genetic
      findings are in good accordance with the ethnohistory of the populations
      compared.

PMID- 8992948
TI  - [Distribution of Rhesus haplotype frequencies in the Cologne (North Rhine
      Westphalia) administrative district].
AB  - The Rhesus haplotype frequencies and their regional distribution have been
      studied in the administrative area of Cologne, North Rhine-Westphalia. The area
      studied is characterised by a heterogeneous distribution of the haplotypes and by
      missing Hardy-Weinberg conditions. There are higher CDe- and lower cde-haplotype
      frequencies in the south-western part. The distribution of the very rare cDue
      haplotype could be correlated with higher B frequencies in the administrative
      areas of Cologne and Dusseldorf.

PMID- 8992949
TI  - [Correlation between physical development and dentition based on the Jena
      Longitudinal Study].
AB  - In this paper body height, body weight and several head measurements from
      children with different dental age were compared. In addition it was
      investigated, if the increasing rates in the body and head measurements in the
      separate dentition. It could be shown, that in body measurements as well as in
      head measurements late teether seem to have a tendency to the smallest mean
      values, early teether show a tendency to higher mean values. This trend is in
      girls clearer than in boys. The increasing rates of the body and head
      measurements differ in the separate dentition stages, but do not allow
      conclusions of the dentition process.

PMID- 8992951
TI  - Proceedings of the 5th Symposium on Lactic Acid Bacteria: Genetics, Metabolism
      and Applications. Veldhoven, The Netherlands, 8-12 September 1995.

PMID- 8992952
TI  - Virus taxonomy 1996 - a bulletin from the Xth International Congress of Virology
      in Jerusalem.

PMID- 8992950
TI  - Clinical uses of probiotics for stabilizing the gut mucosal barrier: successful
      strains and future challenges.
AB  - Probiotic bacteria are used to treat disturbed intestinal microflora and
      increased gut permeability which are characteristic to many intestinal disorders.
      Examples include children with acute rotavirus diarrhoea, subjects with food
      allergy, subjects with colonic disorders and patients undergoing pelvic
      radiotherapy and sometimes changes associated with colon cancer development. In
      all such disease states altered intestinal microflora, impaired gut barrier and
      different types of intestinal inflammation are present. Successful probiotic
      bacteria are able to survive gastric conditions and colonize the intestine, at
      least temporarily, by adhering to the intestinal epithelium. Such probiotic
      microorganisms appear to be promising candidates for the treatment of clinical
      conditions with abnormal gut microflora and altered gut mucosal barrier
      functions. They are also promising ingredients to future functional foods and
      clinical foods for specific disease states provided that basic requirements for
      strains and clinical studies are carefully followed.

PMID- 8992953
TI  - [Preparation of the myristoylated and nonmyristoylated form of recombinant
      recoverin in E. coli cells and comparison of their functional activity].
AB  - A recombinant plasmid was constructed for expressing a gene for bovine recoverin
      under the control of the lac promoter. Coexpression of the recoverin and N
      myristoyl transferase genes was performed to prepare recombinant myristoylated
      recoverin. The obtained systems provide high levels of biosynthesis of the
      recombinant recoverins in the E. coli cells. Using a reconstructed system,
      containing urea-washed rod outer segment membranes, purified rhodopsin kinase
      (RK), and a recoverin, it was shown that the three recoverin forms (natural,
      recombinant nonmyristoylated, and recombinant myristoylated ones) perform the
      calcium-dependent regulation of the activity of RK with half a maximum effect at
      a free calcium concentration of 2 microM. Interestingly, the N-terminal
      myristoylation of recoverin increased substantially its functional activity.

PMID- 8992955
TI  - [Biosynthesis of human calcitonin and mini-proinsulin in bacterial cells in the
      form of hybrid proteins with corresponding antisense peptides and a metal-binding
      peptide].
AB  - To verify experimentally the molecular recognition theory, plasmids were
      constructed that provided the efficient synthesis of hybrid proteins composed of
      human calcitonin or miniproinsulin, the corresponding antisense peptides, and a
      histidine-rich metal-binding peptide. A method for isolation of the hybrid
      proteins by metal-chelating chromatography, cleavage, and renaturation was
      developed.

PMID- 8992954
TI  - [Biosynthesis and conformational state of 17-kDa and 27-kDa N-terminal fragments
      of elongation factor EF-2 in solution].
AB  - N-Terminal fragments of the rat liver elongation factor EF-2 containing 162 (17
      kDa) and 244 (27 kDa) amino acid residues of 857 (95 kDa) residues of the native
      protein were synthesized in E. coli cells and in a wheat germ cell-free
      translation system, and their conformations were studied. Both fragments were
      synthesized as inclusion bodies (nonspecific molecular aggregates). The
      conformations of the fragments in a solution were studied at neutral pH values by
      CD, fluorescence spectroscopy, scanning microcalorimetry, viscosimetry, gel
      filtration, limited proteolysis, and interaction with monospecific anti-EF-2
      antibodies and GroEL/ES molecular chaperone. Under nondenaturing conditions, both
      fragments existed in a solution as associates within a broad range of molecular
      masses, contained a considerable amount of elements of the intramolecular
      secondary structure, and represented globules without rigid tertiary structure
      (molten globules). A rigid tertiary structure was not formed even after the
      interaction of the fragments with the GroEL/ES molecular chaperone, thus
      indicating that the C-terminal fragment is essential for the formation of the
      rigid tertiary structure. Both fragments contained conformational antigenic
      determinants similar to those in the whole protein; i.e., despite the absence of
      the rigid tertiary structure, the fragments contained elements whose structure
      was similar to that of the corresponding regions in the whole protein.

PMID- 8992956
TI  - [Mechanism of action of aspartic proteinases. 2. Conformational possibilities of
      an HIV-1 proteinase substrate].
AB  - Theoretical conformational analysis of a hexapeptide fragment p17-p24 of the
      native substrate of the HIV-1 protease was reported. The geometrical and energy
      parameters of all possible optimal conformations were determined. The data which
      are necessary for the calculation of the mechanism of the catalytic act of HIV-1
      protease were obtained.

PMID- 8992957
TI  - [Sequential attachment of arginine residues to peptides, catalyzed by subtilisin.
      1. Effect of organic solvent composition].
AB  - Subtilisin 72 sorbed on a macroporous glass catalyzed the condensation of Dnp(or
      Z)-Ala2-Leu-OCH3 with arginine amide in a mixture of DMSO and acetonitrile at a
      water content less than 0.07% (v/v). This reaction resulted in the sequential
      formation of peptides containing from one to four C-terminal arginine residues.
      The number of attached Arg residues depended on the DMSO concentration in the
      solvent mixture, which determined the local arginine excess on the sorbent
      surface, which significantly exceeded the molar arginine excess in the solution.
      This enzymic reaction opened up new opportunities for preparation of peptides
      with different content of arginine residues.

PMID- 8992958
TI  - [Site-specific BcuAI endonuclease from Bacillus cereus A].
AB  - A new restriction endonuclease was isolated from the Bacillus cereus BKM B-814 by
      means of the cell disruption with ultrasonication, ammonium sulfate fractionation
      of the cell-free extract, and chromatography on DEAE-Sepharose to give about 1400
      U of the enzyme per gram of cells. The enzyme revealed the maximum activity at 30
      37 degrees C, pH 7.6-8.2, and 5-10 mM MgCl2 under a high ionic strength (50 mM
      Tris-HCl, 100 mM NaCl). The site-specific endonuclease BcuAI was found to
      recognize the 5' G decreases G(A/T)CC sequence in double-stranded DNA and cleave
      it as shown with the arrow, thus being a true isoschisomer of the AvaII
      restriction endonuclease.

PMID- 8992959
TI  - [Synthesis and properties of covalently-closed DNA duplexes containing
      pyrophosphate and and substituted pyrophosphate internucleotide groups].
AB  - A new method for the efficient synthesis of covalently closed DNA duplexes (DNA
      dumbbells) and the introduction of pyrophosphate and substituted pyrophosphate
      internucleotide groups into their structure is proposed. The method is based on
      chemical ligation in DNA duplexes that are formed by a polynucleotide the ends of
      which are brought together due to the introduction of the minihairpin structure
      [sequence: see text]. DNA dumbbells containing a pyrophosphate (substituted
      pyrophosphate) group result from the interaction as being between the 3'-terminal
      phosphate (methylphosphate) group of the polynucleotide and the 5'-terminal
      phosphate group of deoxyguanosine of the minihairpin sequence, which flanks the
      polynucleotide from the 5' end. 1-Ethyl-3-(3'-dimethylaminopropyl) carbodiimide
      was used as a condensing agent. The yield of covalently closed 42-mer DNA
      duplexes containing a pyrophosphate group was 98%, that of duplexes with a
      substituted pyrophosphate group was 25%. The reactivity of the substituted
      pyrophosphate group incorporated into DNA dumbbells was studied. It is shown that
      the group efficiently interacts with nucleophiles in an aqueous medium at pH 8.0.

PMID- 8992960
TI  - [Inhibition of cholesterol biosynthesis in rabbit hepatocytes by 3-beta-(omega
      hydroxyalkoxy)cholest-5-enes].
AB  - 3 beta-(2-Hydroxyethoxy)-, 3 beta-(4'-hydroxybutoxy)-, 3 beta-(6-hydroxyhexyloxy)
      , 3 beta-(9-hydroxynonyloxy)-, and 3 beta-(2-hydroxy-2-[3H]ethoxy)cholest-5-enes
      were synthesized. By means of a spin probe, the influence of the synthesized
      compounds on the phase transition of dimyristoylphosphatidylcholine were
      estimated. Time and dose dependences of the incorporation of 3 beta-(2-hydroxy-2
      [3H]ethoxy)cholest-5-ene into rabbit hepatocytes (the primary culture) were
      studied. 3 beta-(2-Hydroxyethoxy)- and 3 beta-(4-hydroxybutoxy)cholest-5-enes
      were shown to inhibit cholesterol biosynthesis from [14C]acetate in rabbit
      hepatocyte cultures upon a 24-hour preincubation.

PMID- 8992961
TI  - [Lipid derivatives of sarcolysin, methotrexate and rubomycin].
AB  - To change the pharmacokinetic properties of the known antitumor agents
      sarcolysine, rubomycin, and methotrexate, their lipid derivatives were
      synthesized with the residues of rac-1,2-dioleoylglycerol and heptadecyl alcohol.
      An ether lipid analog, 3-sarcolysyl 2-methyl-1-octadecyl-sn-glycerol, with the
      lipid moiety being itself an antineoplastic agent was also obtained.

PMID- 8992962
TI  - [New aminooxy analogs of biogenic polyamines].
AB  - A series of structural analogs of putrescine, spermidine, and spermine with the
      aminomethylene fragment substituted by the aminooxy group was suggested. The
      synthesis of the new aminooxy analogs of spermine was described. Biochemical
      aspects of the activity of the aminooxy analogs of polyamines were discussed in
      respect of their selective inhibition of normal and leukemic cells.

PMID- 8992963
TI  - [The in vitro induction of monocyte chemotactic protein-1 and interleukin-8 in
      whole human blood by low molecular weight thymus peptides].
AB  - Thymic peptides show immunoreconstitutive und tumor suppressive effects. They are
      used in oncology to improve the immunological status of patients. Chemokines are
      able to activate immune cells and inhibit tumor growth. In this study it was
      proved whether low molecular thymic peptides are able to increase the secretion
      of the chemokines monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8),
      macrophage inflammatory protein-1 alpha (MIP-1 alpha) and macrophage inflammatory
      protein-1 beta (MIP-1 beta) as well as the cytokine tumor necrosis factor-alpha
      (TNF-alpha) which is not related to chemokines using cell cultures of human whole
      blood. The thymic peptides induced a significant (p < 0.05) elevated secretion of
      MCP-1 and IL-8 whereas for MIP-1 alpha, MIP-1 beta and TNF-alpha no significant
      chances were seen. MCP-1 and IL-8 showed divergent dose-dependent effects and a
      different time kinetic of their secretion. The MCP-1 concentration correlated
      positively with the count of monocytes in whole blood of the volunteers while the
      IL-8 concentration in dependence with the incubation time correlated positively
      with the count of granulocytes or monocytes of the volunteers. The results
      indicate an activation of monocytes and/or granulocytes by low molecular thymic
      peptides followed by selective elevated secretion of MCP-1 and IL-8.

PMID- 8992965
TI  - Are transporter associated with antigen processing (TAP) and tapasin class I MHC
      chaperones?
AB  - Class I MHC heavy chains associate with many proteins in the endoplasmic
      reticulum, including TAP, calnexin, calreticulin, and the newly defined tapasin
      molecule. Recent studies have begun to resolve the nature of how these proteins
      interact with class I as well as the functional significance of each of these
      interactions. We propose here that TAP and tapasin are leading candidates to be
      highly specific chaperones for the class I molecule.

PMID- 8992964
TI  - [The relative bioavailability of paracetamol in suppositories in comparison to
      tablets].
AB  - Relative Bioavailability Studies on Paracetamol in Suppositories as Compared to
      Tablets. Relative bioavailabilities of 250 mg paracetamol (CAS 103-90-2) in ben-u
      ron 125 mg and ben-u-ron 250 mg suppositories were determined in comparison with
      that of cut-in-half Benuron tablets 500 mg in an open intraindividual 3-period
      changeover-study in 18 healthy volunteers. Plasma concentrations of paracetamol
      were analyzed by means of a specific and sensitive HPLC-method with UV-detection.
      For the assessment of the bioavailability AUC, Cmax, tmax and HVD (half value
      duration) were used as pharmacokinetic characteristics. Relative bioavailability
      of paracetamol was 102% for 125 mg and 93% for 250 mg suppositories, compared
      with that of cut-in-half 500 mg tablets. Mean maximum paracetamol plasma
      concentrations (Cmax) were determined as 2.1 micrograms/ml (CV = 31%; (CV =
      Coefficient of Variation), 2.0 micrograms/ml (CV = 27%) and 3.5 micrograms/ml (CV
      = 27%) after administration of 125 mg and 250 mg suppositories and 500 mg cut-in
      half tablets, respectively. These maximum concentrations were achieved 2.2 +/-
      0.7, 1.8 +/- 0.7 and 0.6 +/- 0.3 h (tmax) after administration of the respective
      preparations. The corresponding HVD-values were 3.8 +/- 1.0, 3.5 +/- 0.9 and 1.8
      +/- 0.8 h, respectively. Extent of bioavailability of paracetamol (dose: 250 mg)
      following administration of 125 mg as well as 250 mg suppositories in comparison
      with 500 mg tablets was shown to be equivalent. The results obtained in this
      study confirm the adequate bioavailability of both suppositories compared with
      tablets. On the other hand both suppository preparations were assessed as being
      bioequivalent concerning AUC and Cmax.

PMID- 8992966
TI  - Superantigen-mediated deletion of specific T cell receptor V beta subsets in the
      SCID-hu Thy/Liv mouse is induced by staphylococcal enterotoxin B, but not HIV-1.
AB  - Infection by HIV-1 has been associated with perturbations in the TCR V beta
      repertoire, suggesting the involvement of a superantigen. Among the hallmarks of
      superantigens is the capacity to delete T cells bearing specific TCR V beta
      families in the developing thymus. To verify the presence of a superantigen in
      HIV-1, we analyzed the SCID-hu Thy/Liv TCR V beta repertoire within CD4+CD8+,
      CD4+CD8-, or CD4-CD8+ thymocytes subsets by flow cytometry using a panel of Abs
      recognizing about 60% of the TCR repertoire following injection of SEB or
      infection by two different HIV-1 isolates. Seven days following SEB injection,
      thymocyte subsets bearing TCR V beta 3, V beta 12, V beta 17, and V beta 20, but
      not V beta 5 or V beta 8 , were deleted relative to mock-injected mice. In
      contrast, no changes were observed in the TCR V beta repertoire in CD4+CD8+,
      CD4+CD8-, or CD4-CD8+ thymocyte subsets after infection with HIV-1. The T cell
      depletion caused by HIV-1 infection is most likely not mediated by an HIV-encoded
      superantigen.

PMID- 8992967
TI  - Costimulation of CD28- T lymphocytes by 4-1BB ligand.
AB  - The interaction of the T cell surface protein CD28 with its ligand, B7-1 or B7-2,
      provides a critical costimulatory signal for T cell activation. T cells from CD28
      mice are deficient in a variety of responses, including those to lectins and
      allogeneic spleen cells. However, some immune responses do occur in CD28- mice,
      suggesting the existence of alternate costimulatory pathways. In this work, we
      show that T cells purified from CD28- mice respond to B lymphomas expressing 4
      1BB ligand (4-1BBL), a member of the TNF gene family. This response is inhibited
      by a soluble form of 4-1BB, the T cell surface receptor for 4-1BBL. Thus, 4
      1BBL/4-1BB interaction provides costimulatory signals to T cells independent of
      signaling through the CD28 receptor. We find that 4-1BBL is inducible on splenic
      B cells by CD40 ligand/CD40 interaction or by culturing of splenic dendritic
      cells, treatments that also induce B7 family molecules. CD28- T cells fail to
      respond in an MLR to resting allogeneic spleen cells. However, treatment of
      spleen cells with CD40 ligand renders them competent in activation of CD28- T
      cells. In contrast to results using B lymphomas as APC, soluble 4-1BB fails to
      inhibit the T cell response to activated spleen cells. This failure of soluble 4
      1BB to block an MLR between CD28+ or CD28- T cells and allogeneic spleen cells is
      in contrast to a previous report with CD28+ cells.

PMID- 8992968
TI  - Recognition of a B cell leukemia-associated minor histocompatibility antigen by
      CTL.
AB  - CTL directed against minor histocompatibility Ags (mHag) play a major role in
      antileukemia reactivity after HLA-identical bone marrow transplantation. Some of
      these mHag are restricted to hemopoietic cells, others show a broad tissue
      expression. Therefore, antileukemia reactivity is often associated with graft-vs
      host disease. Here, we report the identification of a B cell leukemia-associated
      mHag, HB-1, recognized by a CD8+ CTL clone derived from peripheral blood of an
      acute lymphoblastic B cell leukemia patient who has been treated by HLA-matched
      bone marrow transplantation. Interestingly, the CTL clone that recognizes HB-1
      exhibits specific cytotoxicity toward leukemic as well as EBV-transformed B
      cells, but not against untransformed B cells. Moreover, the CTL clone does not
      lyse PHA-stimulated T cell blasts, monocytes, and fibroblasts, indicating that HB
      1 is mainly expressed by transformed B cells. Further analysis reveals that HB-1
      is restricted by HLA-B44 (both B*4402 and B*4403) and that 28% of HLA-B44
      positive individuals express HB-1. These findings demonstrate that leukemia
      associated mHag with a restricted tissue distribution, such as HB-1, elicit CTL
      reactivity in vivo. These Ags are of potential use in immunotherapy against
      leukemia because they generate antileukemia reactivity that is not associated
      with graft-vs-host disease.

PMID- 8992969
TI  - Induction and prevention of colonic inflammation in IL-2-deficient mice.
AB  - Gene-targeted mice deficient for IL-2 (IL-2 -/- mice) are free of apparent
      disease when maintained under germfree conditions but develop colitis and
      autoimmunity in a conventional environment. Here we show that colitis can be
      reproducibly induced in IL-2 -/- mice, but not in IL-2 +/+ mice, by i.p.
      immunization with Ag in CFA; thus enabling the systematic study of the
      immunopathogenesis of the colitis. We found that TNP-KLH or TNP-OVA had the most
      significant effect in inducing colitis, and while TNP-KLH immunization leads to
      the early appearance of activated T cells in the colons of both IL-2 -/- and IL-2
      +/+ mice, only lamina propria cells of IL-2 -/- mice produced high amounts of INF
      gamma. Moreover, both infiltrating colon CD4+ (69%) and CD8+ (6%) T cells secrete
      large amounts of IFN-gamma; however, only the depletion of CD4+ T cells leads to
      abrogation of the inflammation. In further analysis, we showed that the high IFN
      gamma production is IL-12 driven, since colonic tissues of IL-2 -/- mice but not
      IL-2 +/+ mice show the presence of heterodimeric IL-12 and co-administration of
      anti-IL-12 with TNP-KLH completely prevented colitis and significantly reduced
      IFN-gamma production. Finally, we demonstrate that IL-2 -/- mice are deficient in
      their ability to induce Th2 responses after TNP-KLH challenge and that such
      immunization also leads to autoimmune-like phenomena in other organs of IL-2 -/-
      mice. These findings suggest that in the absence of IL-2 systemic administration
      of Ag induces primarily Th1 cells driven by overexpression of heterodimeric IL
      12.

PMID- 8992970
TI  - Homing potentials of circulating lymphocytes in humans depend on the site of
      activation: oral, but not parenteral, typhoid vaccination induces circulating
      antibody-secreting cells that all bear homing receptors directing them to the
      gut.
AB  - Specific Ab-secreting cells (ASC) appear in the human blood as a response to oral
      and parenteral vaccination. The actual contribution of these cells to the defense
      of the body depends on their final effector site. The homing potentials of
      mucosally and parenterally induced ASC were compared by examining the homing
      receptor (HR) expression of circulating specific ASC in the blood of volunteers
      vaccinated orally or parenterally with the same Ag, Salmonella typhi Ty21a.
      Circulating lymphocytes were separated into receptor-positive and -negative
      populations, and the numbers of specific ASC were assayed. The alpha4 beta7
      integrin, which acts as a gut HR, was expressed on all (99%) of the mucosally
      activated ASC, but on only 58% of the parenterally induced ASC or 58% of all Ig
      secreting cells of the unvaccinated controls. L-selectin, the peripheral lymph
      node HR, showed an inverse distribution; it was found on 42% of mucosally
      activated ASC and on 86% of parenterally induced ASC. These results reveal that
      all of the circulating ASC after oral vaccination are committed to migrate to the
      mucosal compartment of the immune system, strongly arguing for a recirculation of
      activated mucosal cells in humans. By contrast, ASC induced by parenteral
      vaccination with the same Ag are mostly directed to the systemic compartment, yet
      a part of them has mucosal homing attitudes as well. These differences indicate
      that the site of Ag encounter determines the homing potential of the cell.

PMID- 8992972
TI  - Carrier-independent hapten recognition and promiscuous MHC restriction by CD4 T
      cells induced by trinitrophenylated peptides.
AB  - The elucidation of mechanisms underlying the recognition of haptens by class II
      MHC-restricted T cells is instrumental for the understanding of chemical- and
      drug-induced allergies. We have previously demonstrated that trinitrophenyl (TNP)
      peptides represent dominant antigenic epitopes for CD8+ and CD4+ mouse T cells
      triggered by chemically TNP-modified APC. Here, we report the characterization of
      TNP-specific, CD4+ mouse T cell lines and hybridomas that were induced in vivo
      and in vitro by defined hapten-conjugated peptides. These peptides, which we had
      previously shown to induce contact sensitivity to picryl chloride in vivo
      regardless of sequence homologies to mouse proteins, were found to activate
      carrier-independent TNP-specific T cells in vitro. We interpret these findings to
      support our view that carrier-independent T cells, reactive to particularly
      repetitive hapten epitopes, may play a crucial role in allergies to chemicals and
      drugs. In addition to carrier independence, one of our hybridomas (IT-H6/A11)
      exhibited a striking promiscuity of MHC restriction. Although absolutely
      dependent in its TNP reactivity on the presence of MHC class II molecules, the IT
      H6/A11 hybridoma completely ignored class II polymorphism and even reacted to TNP
      peptides presented on human DR molecules. Regarding hapten allergies in humans
      with a heterozygous situation for three types of class II molecules (DR, DP, and
      DQ), such promiscuous MHC restriction should lead to the presentation of even
      higher epitope densities to the respective T cell clones. Hybridoma IT-H6/A11,
      reacting to TNP independent of carrier peptide and of MHC haplotype, also allowed
      for an unusually systematic study of the minimal requirements for TNP
      recognition. Despite an almost complete ignorance of amino acid side chains on
      the carrier peptide, our data indicate a clearly position-specific interaction of
      hapten and TCR.

PMID- 8992971
TI  - Analysis of CD28 cytoplasmic tail tyrosine residues as regulators and substrates
      for the protein tyrosine kinases, EMT and LCK.
AB  - The CD28 cell surface receptor provides an important costimulatory signal for T
      cells necessary for their response to Ag. Early events in CD28 signaling include
      recruitment and activation of phosphatidylinositol 3-kinase (PI3-kinase) and
      activation of the protein tyrosine kinases (PTKs), LCK and EMT. Recruitment and
      activation of PI3-kinase is known to be dependent upon phosphorylation of
      tyrosine 173 of the CD28 cytoplasmic tail contained within a YMNM motif. By
      contrast, little is known of which residues of the CD28 tail, including
      tyrosines, are required for the activation of PTKs. To address this we studied
      the ability of truncation mutants and tyrosine to phenylalanine substitution
      mutants of the CD28 cytoplasmic tail to activate LCK and EMT in Jurkat T leukemia
      cells. Our results indicate that 1) activation of EMT is partially dependent upon
      tyrosine 173 of the CD28 tail, although it does not require PI3-kinase
      activation; 2) activation of LCK is independent of CD28 cytoplasmic tail tyrosine
      residues; and 3) elements sufficient for the activation of both kinases are
      contained within the first half of the tail. In addition we studied the CD28 tail
      as a substrate for both PTKs in in vitro kinase assays. We demonstrate that EMT
      can phosphorylate all four tyrosines of the CD28 tail, in contrast to LCK, which
      phosphorylates only tyrosine 173. Together with evidence that in vivo, tyrosines
      other than tyrosine 173 become phosphorylated following CD28 stimulation, this
      finding suggests that, like LCK, one function of EMT during CD28 signaling is
      phosphorylation of the receptor.

PMID- 8992973
TI  - TNF receptor-2-triggered apoptosis is associated with the down-regulation of Bcl
      xL on activated T cells and can be prevented by CD28 costimulation.
AB  - Stimulation of recently activated T cells results in apoptosis of the responding
      cells, a process referred to as activation-induced cell death. This process is
      believed to play an important role in the regulation of immune homeostasis and is
      suggested to be mediated mainly by interactions between Fas and Fas ligand.
      Recent evidence indicates that TNF-alpha and TNFR2 interaction plays an important
      role in down-regulating activated T cells. The role of TNFR2 signaling in
      activation-induced cell death, however, has not been directly examined. We
      demonstrate here that 48-h activated T cells are most sensitive to TNFR2-induced
      apoptosis. Cross-linking of TNFR2 on activated T cells results in down-regulated
      protein and mRNA expression of Bcl-xL. Furthermore, CD28 costimulation can
      prevent anti-TNFR2-induced apoptosis and restore Bcl-xL expression. These results
      have potential implications for understanding the role of TNFR2 signaling in the
      regulation of T cell responses.

PMID- 8992974
TI  - The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10
      receptor.
AB  - BCRF1 is an EBV homologue of human IL-10 (hIL-10) and is known as viral IL-10
      (vIL-10). As found earlier for the effects of vIL-10 on mouse mast cells and CD4+
      T cells, the efficiency of inhibition by vIL-10 of IL-2 production by human CD4+
      T cell clones is approximately 1000-fold diminished compared with hIL-10. We
      studied the interaction of vIL-10 and an epitope-tagged homologue, vIL-10His6,
      with recombinant mouse and human IL-10 receptors (mIL-10R, hIL-10R). vIL-10His6
      has approximately 1000-fold lower affinity for recombinant IL-10R than does hIL
      10, yet stimulates proliferation of mouse Ba/F3 (BaF)-mIL-10R- and human TF1-hIL
      10R-transfected cells with a sp. act. comparable to or greater than that of the
      cellular cytokine. In contrast, BaF-hIL-10R cells are approximately 1000-fold
      less sensitive to vIL-10His6 than are BaF-mIL-10R cells. An anti-hIL-10R mAb
      (3F9) blocks responses to both hIL-10 and vIL-10His6, while a soluble form of hIL
      10R effectively neutralizes biologic responses only to hIL-10 by both BaF-IL-10R
      transfectants and normal human peripheral blood cells. The results indicate that
      biologic responses to both hIL-10 and vIL-10 require the known IL-10R, and
      suggest the existence of at least one additional IL-10R subunit. We suggest that
      vIL-10 is a selective agonist that is impaired in its ability to bind the defined
      IL-10R, which we now designate as IL-10R alpha.

PMID- 8992977
TI  - T cell-derived IL-4 and dendritic cell-derived IL-12 regulate the lymphokine
      producing phenotype of alloantigen-primed naive human CD4 T cells.
AB  - Previous studies on human Th subset development were restricted to the analysis
      of naive T cells activated with anti-CD3 mAb in the absence of physiologic APC.
      In this study, we have analyzed the role of cytokines and physiologic APC on T
      cell maturation in an Ag-specific system, in which naive neonatal CD4 T cells
      were primed with allogeneic dendritic cells (DC). We found that the cytokine
      profile of primed cells was dependent upon 1) the ratio between T cells and
      allogeneic DC and 2) the endogenous production of IL-4 and IL-12. Neutralization
      of IL-4 during primary MLR increased IFN-gamma production at priming and shifted
      the phenotype of primed cells from Th0 to Th1. These effects were IL-12
      dependent, in that they were suppressed by anti-IL-12 Abs. The production of IL
      12 in primary MLR was further evidenced by the presence of IL-12 p40 in the
      culture supernatant fluids. IL-12 production was suppressed by exogenous IL-4 and
      increased by anti-IL-4 blocking mAbs, indicating that endogenous IL-4 down
      regulated IL-12 production by DC. Finally, IL-12 was produced as a result of T
      cell/DC interaction involving the CD40/CD40 ligand and CD28/B7 costimulation
      pathways, as revealed by the inhibitory effect of anti-CD40 ligand mAb and CTLA
      4Ig. These observations suggest that in neutral conditions, Ag presentation by DC
      results in the coordinate production of naive T cell-derived IL-4 and DC-derived
      IL-12 that in concert shape the cytokine profile of Th cells.

PMID- 8992975
TI  - IFN-gamma-activated primary murine astrocytes express B7 costimulatory molecules
      and prime naive antigen-specific T cells.
AB  - Astrocytes may serve as effectual APCs for T cell-mediated immune responses to
      myelin components during multiple sclerosis and experimental autoimmune
      encephalomyelitis (EAE). Although astrocytes have been reported not to
      constitutively express MHC class II molecules, expression is up-regulated during
      active EAE and by in vitro incubation with IFN-gamma. Previous studies have
      reported that cytokine-activated astrocytes are able to activate Ag-specific
      previously activated T cells, but not naive alloreactive T cells. In the current
      study, we show that a subset of primary murine astrocytes constitutively
      expresses B7-2 molecules, as determined by FACS and PCR analyses, and up
      regulates surface expression and mRNA levels of both B7-2 and B7-1 upon IFN-gamma
      stimulation. In contrast to earlier reports, we found that both untreated and IFN
      gamma-treated astrocytes were able to stimulate proliferation of previously
      activated OVA-specific Th1 cells. In contrast, only IFN-gamma-treated astrocytes
      activated naive, transgenic OVA-specific T cells. Astrocyte-induced activation of
      both OVA-specific naive T cells and activated Th1 cells was dependent primarily
      on B7-2-mediated costimulation, as proliferation was inhibited by CTLA4-Ig and by
      anti-B7-2 mAbs. These results suggest that astrocytes in an inflammatory
      environment have the capacity to express the required MHC class II and B7
      costimulatory molecules necessary for efficient activation of naive T cells.
      Since we have shown that T cells specific for endogenous myelin epitopes released
      during acute EAE play the major pathologic effector role in subsequent disease
      relapses (epitope spreading), astrocytes could play a role in the local
      activation and expansion of these responses.

PMID- 8992976
TI  - Mechanisms regulating telomerase activity in murine T cells.
AB  - Telomeres shorten with successive cell divisions in normal somatic cells, while
      telomerase plays an important role in maintaining their lengths. Although
      telomerase activity was originally described as being expressed exclusively by
      immortal cells and germline cells, a recently developed PCR-based technique
      (telomeric repeat amplification protocol (TRAP)) has revealed that normal
      peripheral blood leukocytes also exhibit this activity following mitogenic
      stimulation. In this study, we examined mechanisms by which mitogenic stimuli up
      regulated telomerase activity in T cells. Splenic T cells freshly isolated from
      BALB/c mice exhibited only negligible telomerase activity. When stimulated with
      Con A or immobilized anti-CD3 mAb at 10 microg/ml, they acquired an increased
      telomerase activity and maximal proliferation. By contrast, T cells treated with
      a much lower concentration (0.03 microg/ml) of anti-CD3 mAb required exogenous IL
      2 for telomerase activation and proliferation. Likewise, adult thymocytes treated
      with anti-CD3 mAb exhibited telomerase activation and proliferation only in the
      presence of exogenous IL-2, IL-4, IL-7, or IL-15. Furthermore, IL-2 alone was
      sufficient for telomerase activation in Con A blasts. These results illustrate a
      pathway through which cytokine receptors transduce telomerase activation signals
      in T cells. Although telomerase activation was concomitant with cell growth in
      normal T cells, we have identified T cell lines that showed discrepancies; the
      CTLL-2 line showed constitutive telomerase activity regardless of cell
      proliferative state, whereas the 7-17 line proliferated vigorously in response to
      IL-2, IL-7, or IL-15, without detectable telomerase activity. Thus, telomerase
      activity, which is ordinarily associated with proliferation in normal T cells, is
      not necessarily required or sufficient for cell growth.

PMID- 8992978
TI  - The role of B7-1 and LFA-3 in costimulation of CD8+ T cells.
AB  - This study compares the ability of LFA-3 (CD58) and B7-1 (CD80) ligands to
      provide costimulatory signals for superantigen (SAg)-stimulated CD8+ and CD4+ T
      cells. We show that B7-1 and LFA-3 costimulation activate CD8+ T cells to
      proliferation, cytokine production (IL-2, TNF, and IFN-gamma), and cytotoxicity.
      A long-lasting proliferative response was observed after combined DR/B7-1/LFA-3
      costimulation. Detailed analysis of SEA-activated CD8+ T cells revealed that
      maximal production of IFN-gamma was seen in LFA-3-costimulated cells, while
      production of IL-2 was mainly induced after B7-1 costimulation. A fivefold
      increase in the IFN-gamma production was observed when activated CD8+ T cells
      were costimulated with Chinese hamster ovary (CHO)-DR/LFA-3 cells compared with
      the secretion induced by CHO-DR/B7-1. In contrast, SEA-treated CD4+ T cells
      costimulated with B7-1 or LFA-3 gave rise to a similar production of IFN-gamma,
      suggesting a preferential function for the CD2/LFA-3 pathway in the regulation of
      IFN-gamma in CD8+ T cells. Moreover, the generation of CTL was supported
      similarly by B7-1 and LFA-3 costimulation, but not by CHO-DR cells. We conclude
      that ligation of the CD28 and CD2 receptors mediate distinct effect on CD8+ and
      CD4+ T cell effector functions.

PMID- 8992979
TI  - Differential effects of IL-12 receptor blockade with IL-12 p40 homodimer on the
      induction of CD4+ and CD8+ IFN-gamma-producing cells.
AB  - The role of IL-12 role in regulating Th1/Th2 balance is attributed in part to the
      ability of this cytokine to induce IFNgamma production by NK and Th1 cells, which
      in turn promotes Th1 and inhibits Th2 development. In the present study, the
      requirement for IL-12 in the development of alloantigen-reactive Th1 was assessed
      by adding neutralizing anti-IL-12 Abs or the IL-12 receptor antagonist p40
      homodimer to primary MLC. The resulting cell populations were assessed for Th1
      development by measuring IFN-gamma production upon restimulation with
      alloantigens. While the addition of anti-IL-12 Abs to primary MLC did not
      influence subsequent cytokine production, addition of p40 homodimer markedly
      enhanced, rather than decreased, Th1 development. To determine which T cell
      population produced enhanced levels of IFN-gamma in response to p40 homodimer,
      CD4+ or CD8+ T cells were depleted from the MLC. While p40 homodimer was
      inhibitory to selected CD4+ Th1 development, it enhanced IFN-gamma production by
      CD8+ T cells. To test the in vivo relevance of these findings, mouse heterotopic
      cardiac allograft recipients were treated with either p40 homodimer, anti-CD8
      mAb, or with both p40 homodimer and anti-CD8 mAb. Treatment of allograft
      recipients with p40 homodimer had no effect on the in vivo sensitization of IFN
      gamma-producing cells and resulted in accelerated allograft rejection relative to
      unmodified recipients. However, p40 homodimer markedly prolonged allograft
      survival in mice depleted of CD8+ T cells. Hence, p40 homodimer stimulates CD8+
      Th1 development in vitro but inhibits CD4+ T cell function both in vitro and in
      vivo.

PMID- 8992980
TI  - Visualization of antigen-specific T cell activation and cytokine expression in
      vivo.
AB  - A transgenic TCR adoptive transfer system was used to visualize Ag-specific T
      cell activation and cytokine expression in vivo. After s.c. injection of peptide
      in adjuvant the entire Ag-specific population up-regulated IL-2 receptor alpha
      chain expression, underwent blast transformation, and developed a memory-surface
      phenotype. A minority of the Ag-specific T cells produced predominantly IL-2 mRNA
      and localized at the T cell/B cell junction in draining lymph nodes. In the
      secondary response, a mixed cytokine pattern of both Th1 and Th2 cytokines was
      demonstrated. When peptide was administered i.v. without adjuvant, 50% of the Ag
      specific cells expressed IL-2, but the peak of expression occurred before IL-2
      receptor alpha-chain up-regulation, and only a minority of the Ag-specific T
      cells underwent blast transformation.

PMID- 8992981
TI  - CD28 costimulation promotes the production of Th2 cytokines.
AB  - CD28 ligation augments TCR-mediated proliferation, IL-2 production, and T cell
      survival. However, the role of CD28 costimulation in T cell differentiation
      remains controversial. To address this issue, CD28+ and CD28-deficient TCR
      alphabeta transgenic (Tg) mice were used to examine cytokine production by T
      cells following antigenic stimulation. Increasing CD28 ligation resulted in
      increased production of IL-4 and IL-5, consistent with differentiation toward a
      Th2 phenotype, in both CD4+ TCR Tg T cells and CD8+ TCR Tg T cells. The same
      result was obtained with CD4+ TCR Tg mice bred to RAG2-deficient mice, indicating
      that the Th2 differentiation observed with increased CD28 ligation was not due to
      the presence of memory T cells. Although CD28 costimulation is an essential
      factor regulating IL-2 synthesis, differentiation toward a Th2-like phenotype by
      CD28 ligation was not an indirect effect of enhanced IL-2 production. In
      contrast, blockade of IL-4 during the primary cultures of the T cells resulted in
      a profound inability to produce Th2-type cytokines upon restimulation. The
      critical role of IL-4 was confirmed by the finding that CD28-deficient TCR
      alphabeta Tg+ T cells cultured with rIL-4 differentiated into Th2-like T cells.
      Therefore, CD28 ligation promotes the production of Th2-type cytokines by naive
      murine T cells via an IL-4-dependent mechanism.

PMID- 8992982
TI  - B220 expression by T lymphoid progenitor cells in mouse fetal liver.
AB  - The present study has characterized T lymphoid progenitor cells that reside in
      mouse fetal liver. Day 14 fetal liver contains progenitor cells that can
      differentiate into mature T cells upon being transferred into the thymus by
      hanging drop cultures. Fractionation of fetal liver cells indicated that T
      progenitor cells were confined in TER119- CD45+ FcR(low) cells. To our surprise,
      B220+ rather than B220- fraction in TER119- CD45+ FcR(low) fetal liver cells
      exhibited efficient progenitor activity generating T cells. Progenitor activity
      by the B220+ fetal liver cells was restricted to T cells, B cells, and
      macrophages at frequency approximately 1/10, approximately 1/10, and
      approximately 1/20, respectively, of isolated B220+ cells. B220+ fetal liver
      cells did not contain detectable D-J rearrangement of TCR-beta gene and were c
      kit+ IL-7R+ Thy-1- CD3- CD4(low) CD8- CD25- CD44+. B220+ fetal liver cells
      expressed mRNAs encoding TCR-beta, pT alpha, Ig alpha, and VpreB. Interestingly,
      TCR beta-chains were expressed by B220+ fetal liver cells in the VDJ-rearranged
      TCR-beta-transgenic mice, indicating that TCR-beta transcription and B220
      expression are activated simultaneously by the transgenic B220+ fetal liver
      cells. These results indicate that B220 is expressed by fetal liver lymphoid
      progenitor cells that can become T cells, and suggest that lymphoid progenitor
      cells in fetal liver concurrently undergo T- and B-specific molecular events
      within a single cell.

PMID- 8992983
TI  - Integrin-associated protein (CD47) is a comitogenic molecule on CD3-activated
      human T cells.
AB  - IAP is a glycoprotein functionally and physically associated with some integrins,
      i.e., the leukocyte response integrin and the beta3 integrin chain on placenta,
      platelets, and polymorphonuclear cells. IAP may act as a transducer element in
      activation mediated via these integrins. Since IAP is present at high density on
      peripheral T lymphocytes we have investigated its involvement in T cell
      activation. We tested three mAbs against IAP, namely B6H12, BRIC126, and 2D3,
      which recognize two distinct epitopes. IAP cross-linking with B6H12 or BRIC126,
      but not 2D3, transduces costimulatory signals within highly purified CD3
      activated T lymphocytes, i.e., enhancement of proliferation, CD25 expression, and
      IL-2 secretion, while no effect was observed upon CD2 stimulation. However, we
      could not observe any functional association between IAP and integrins on
      peripheral T cells. In an attempt to explore further the activation signal
      delivered by IAP, we show here that IAP cross-linking with the comitogenic B6H12
      mAb induces the phosphorylation on tyrosine of several proteins, one of which is
      identified as p56(lck) protein tyrosine kinase. Moreover, we observed that IAP is
      associated with p56(lck) on PMA-activated, but not on resting, T cells. These
      data suggest that on T cells, IAP may be involved directly via a specific ligand
      in cell-matrix or cell-cell interactions. Such interactions could trigger protein
      tyrosine phosphorylation pathways, which play an important role in both
      maturation and activation of T cells.

PMID- 8992984
TI  - Presentation of an influenza nucleoprotein epitope incorporated into the H-2Db
      signal sequence requires the transporter-associated with antigen presentation.
AB  - In an effort to optimize the formation of peptide-specific CTL target structures
      in the context of plasmid DNA immunization, a strategy was developed to couple
      the biosynthesis of a class I heavy chain with its optimal binding epitope.
      Specifically, a cDNA expression vector was constructed with the influenza
      nucleoprotein epitope NP366-74 incorporated into the signal sequence of its
      restriction element H-2Db. Transporter associated with Ag presentation-expressing
      murine cell lines P815 (H-2d) and BW5147 (H-2k) transfected with this modified
      heavy chain expressed normal levels of plasmid-encoded Db at the cell surface,
      and were lysed by NP366-74-specific CTL. These results indicate that the modified
      signal sequence was successfully delivered to the endoplasmic reticulum, and the
      epitope within it processed for T cell recognition. In contrast, T2 cells, which
      lack the TAP transporter, when transfected with the same vector were not lysed by
      NP366-74 CTL, and exhibited an Ag-processing-defective phenotype. Thus, these
      data, which indicate TAP-dependent presentation of an optimal CTL epitope located
      in a signal sequence, challenge the effectiveness of Ag processing in the
      endoplasmic reticulum.

PMID- 8992985
TI  - Antigen-presenting cells in the thymus that can negatively select MHC class II
      restricted T cells recognizing a circulating self antigen.
AB  - We investigated Ag presentation of an extracellular self Ag (C5), which only
      reaches the thymus via the blood circulation, for negative selection of MHC class
      II-restricted, C5-specific T cells. Thymic APC were introduced into fetal thymic
      reaggregation culture with thymocytes from C5-specific TCR transgenic mice to
      follow the development of C5-specific T cells in the presence or the absence of
      self Ag presented by various APC. To mimic the physiologic distribution of C5
      peptide/MHC class II complexes on thymic APC as closely as possible, they were
      isolated from thymi of C5+ mice, so that the amount of C5 peptide bound to MHC
      class II on their surface would reflect the amount of self Ag they have access to
      and process normally in vivo. This circumvented the problems related to
      artificially high doses of Ag or peptide in vivo or in vitro, that might obscure
      physiologic differences such as the capacity to internalize and process Ag. The
      results show that not only thymic dendritic cells, but also cortical and
      medullary epithelial cells were able to induce negative selection of C5-specific
      thymocytes with similar efficiency. In contrast, thymic macrophages were unable
      to influence the development of C5-specific T cells. Their failure to present
      exogenous self Ag for negative selection suggests that macrophages concentrate on
      their primary function in the thymus, the disposal of dying thymocytes.

PMID- 8992986
TI  - Analysis of initial attachment of B cells to endothelial cells under flow
      conditions.
AB  - This study examined the adhesive interactions of peripheral blood B cells with
      TNF-alpha-activated endothelial monolayers, and analyzed the roles of E-selectin,
      P-selectin, or VCAM-1 molecules expressed on activated HUVEC. B cell interaction
      occurred on activated HUVEC, but not on resting HUVEC under flow conditions. The
      majority of peripheral blood B cells expressed P-selectin glycoprotein ligand-1
      and alpha4 integrin. However, the expression of cutaneous lymphocyte Ag on B
      cells was low. Under flow conditions, B cells could bind to P-selectin-coated
      tubes and VCAM-1-transfected Chinese hamster ovary cells. In contrast, B cells
      could not bind to E-selectin-coated tubes. Adhesion activity of B cells to P
      selectin-coated tubes was weaker than that of T cells. Furthermore, adhesion
      activity of B cells to VCAM-1-transfected Chinese hamster ovary cells was similar
      to that of T cells. Treatment of activated HUVEC with anti-VCAM-1 mAb reduced
      interaction of B cells under flow conditions. However, the treatment of activated
      HUVEC with anti-P-selectin mAb did not reduce interaction. These data indicated
      that the interaction of VCAM-1 with alpha4 integrin plays a major role in an
      initial attachment of B cells to endothelial monolayers under flow conditions.

PMID- 8992987
TI  - Constitutive expression of terminal deoxynucleotidyl transferase in transgenic
      mice is sufficient for N region diversity to occur at any Ig locus throughout B
      cell differentiation.
AB  - N region diversity in Ag receptors is a developmentally regulated process in B
      and T cells that correlates with the differential expression of terminal
      deoxynucleotidyl transferase (TdT). Absent in fetal and newborn mice, TdT
      expression is restricted to early T and pro-B cells in adults. To extend the TdT
      expression pattern throughout B cell ontogenesis, we generated transgenic mice
      carrying a TdT cDNA under the regulatory elements of the N-myc gene and the IgH
      enhancer. High expression was observed in secondary lymphoid organs consistent
      with TdT activity beyond the pre-B cell stage. This suggests that TdT transgene
      expression is not down-regulated as is the endogenous gene. Unlike normal mice,
      extensive N region diversity was found in rearranged lambda light chain genes of
      adult transgenic animals. Therefore, expression of TdT appears sufficient for N
      region diversity to occur at any Ig locus. More importantly, expression of the
      transgene takes place during fetal development. As a consequence, the potential
      fetal B cell repertoire is modified as both rearranged heavy and light chain
      genes now show N region additions. Constitutive expression of TdT throughout B
      cell differentiation does not therefore appear deleterious and suggests that TdT
      is recruited only to participate in the V(D)J recombination process.

PMID- 8992988
TI  - Elimination of N-linked glycosylation sites from the human IgA1 constant region:
      effects on structure and function.
AB  - IgA1 Abs possess conserved N-linked glycosylation sites in the second C region
      and secreted tailpiece domains. To understand the role of these carbohydrates in
      the structure and function of human IgA1, site-directed mutants that produce
      human IgA1 lacking either one or both of the N-linked carbohydrate sites have
      been produced. When the mutant heavy chains are expressed in myeloma lines
      producing the relevant kappa-light chain, efficient secretion of the monomer and
      dimer forms of IgA1 is seen. In addition, higher polymer forms of the IgA
      molecules lacking the third domain carbohydrate, either singly or in the double
      mutant, are present. Functional analysis of the IgA1 proteins has shown
      significant differences between the various mutants and wild-type IgA. The
      carbohydrate mutants show a reduced affinity for their target Ag, dansyl. All of
      the IgA1 molecules retained the ability to bind to the polymeric Ig receptor. C3
      binding was observed for all of the IgA molecules, with the IgA mutants lacking
      the third domain carbohydrate showing a reduced ability to bind C3; however, IgA
      did not effectively activate the alternative pathway, as determined by factor B
      cleavage and terminal complex binding. These studies demonstrate that N-linked
      glycosylation in the constant domain of human IgA1 plays an important role in the
      biologic properties of IgA1.

PMID- 8992989
TI  - The hinge as a spacer contributes to covalent assembly and is required for
      function of IgG.
AB  - Chimeric IgG3 lacking a genetic hinge but with Cys residues in CH2 between
      position 231 and 232 (IgG3 deltaH+Cys) and position 279 (IgG3 deltaH+2Cys)
      produced by site-directed mutagenesis have been found to be deficient in their
      intermolecular assembly. Although some H2L2 molecules are formed, significant
      quantities of assembly intermediates, in particular HL, are found in the
      secretions. Both IgG3 deltaH+Cys and IgG3 deltaH+2Cys were greatly reduced in
      their ability to bind Fc gammaRI. They also failed to bind C1q and activate the
      complement cascade. Addition of the tailpiece from IgM (microtp) to IgG3
      deltaH+Cys (yielding IgG3 deltaH+Cys microtp) failed to lead to efficient
      oligomerization. IgG3 deltaH+Cys microtp failed to bind Fc gammaRII. However, at
      high concentrations it was able to bind C1q and effect complement-dependent
      cytolysis. It consumed complement in the absence of added Ag, indicating that
      removing the flexible hinge was not sufficient to yield polymeric IgG that
      resembled IgM in its dependence on added Ag for complement activation.

PMID- 8992990
TI  - Mapping of the catalytic and epitopic sites of human CD38/NAD+ glycohydrolase to
      a functional domain in the carboxyl terminus.
AB  - We reported that 1) ecto-NAD+ glycohydrolase (NADase) activity induced upon
      differentiation of HL-60 cells is localized on the extracellular carboxyl
      terminal side of CD38 and that 2) CD38 ligation by specific mAbs is followed by
      protein tyrosine phosphorylation in the cells. The strategy selected for
      identifying the relevant catalytic domains of the molecule relies upon the
      production in COS-7 cells of carboxyl-terminal deletion mutants of CD38. The
      mutants with fewer than 15 amino acids deleted at the carboxyl terminus of the
      300-amino acid wild-type molecule maintained NADase activity, whereas those with
      more than 27 amino acids deleted did not. The general inference is that the
      carboxyl-terminal 273-285 sequence bears the site of enzyme activity.
      Introduction of site-directed mutation of a conserved cysteine residue (Cys275),
      located in the 273-285 sequence, completely abolished NADase activity. The second
      issue resolved in this work is the definition of an epitope of the agonistic anti
      CD38 mAbs. To this aim, a panel of selected anti-CD38 mAbs was tested using these
      mutants and various CD38 fragments as the target in immunoblot analyses. All of
      the epitopes recognized by mAbs inducing protein tyrosine phosphorylation were
      mapped on an identical site containing the carboxyl-terminal sequence of 273-285.
      The conclusion is that the discrete carboxyl-terminal sequence identified in the
      present study not only plays a key role in its ecto-NADase activity, but actually
      constitutes the epitopes exploited by the agonistic anti-CD38 mAbs for
      transmembrane signaling.

PMID- 8992991
TI  - Intracellular IL-1 receptor antagonist promoter: cell type-specific and inducible
      regulatory regions.
AB  - The objective of these studies was to examine the molecular mechanisms involved
      in transcriptional regulation of the gene for the intracellular structural
      variant of the IL-1 receptor antagonist (icIL-1Ra) molecule. By reverse
      transcription-PCR analysis, constitutive expression of endogenous icIL-1Ra mRNA
      was observed in the epithelial cell lines A431 and HT-29, but not in the
      macrophage cell lines RAW 264.7 and U937, or in the lymphocyte cell lines Raji
      and Jurkat. However, icIL-1Ra mRNA expression was observed in response to
      stimulation with LPS in RAW 264.7 cells and to PMA and LPS in U937 cells. To
      examine the mechanisms of transcriptional regulation, 4.5 kb of the 5' flanking
      sequence was isolated from the human icIL-1Ra gene, sequenced, cloned into a
      luciferase expression vector (pIC4525.Luc), and examined in transfection studies.
      The pIC4525.Luc construct exhibited a pattern of expression in epithelial and
      macrophage cell lines similar to that of the endogenous icIL-1Ra gene. To obtain
      a generalized map of cell type-specific and inducible cis-acting DNA elements,
      nested 5' deletional mutants of the icIL-1Ra promoter were constructed. Results
      from transfection studies with these icIL-1Ra promoter/luciferase fusion
      constructs indicated that constitutive expression in epithelial cells was under
      the control of three positively acting regions located between bases -4525 to 
      1438, -288 to -156, and -156 to -49. In contrast, basal expression of pIC4525.Luc
      in transfected but unstimulated RAW 264.7 cells was under the control of a weak
      inhibitory region located between bases -4525 to -1438 and a strong positive
      element between -156 and -49. LPS induction of icIL-1Ra transcription in RAW
      264.7 cells was regulated by strong positively acting DNA regions between bases 
      1438 to -909 and -156 to -49. In summary, the proximal region of the icIL-1Ra
      promoter, between bases -156 to -49, contains positive cis-acting elements that
      are needed for expression in both epithelial and monocyte cell lines. However,
      our results indicate that the ability of this proximal promoter region to control
      expression is strongly influenced, both positively and negatively, by other
      upstream cis-acting elements in a cell type-specific manner.

PMID- 8992992
TI  - The IL-13 receptor structure differs on various cell types and may share more
      than one component with IL-4 receptor.
AB  - We have reported on the expression and characteristics of IL-13R and have
      demonstrated that IL-13 competes for IL-4 binding while IL-4 did not compete for
      the IL-13 binding on some cell types. Based on these observations, and the size
      of IL-13 and IL-4 cross-linked proteins, we concluded that the receptor for IL-13
      is complex and shares a subunit with the receptor for IL-4. To explore the
      complexity of the IL-13R, a wide variety of cell types was examined for IL-13 and
      IL-4 binding. We report in this work that IL-4 does not always bind well to cells
      that bind IL-13, but the reverse is also true. We also found that IL-4 can
      compete more effectively for IL-13 binding than IL-13 itself. Cross-linking
      studies support these observations and demonstrate that 125I-labeled IL-13 bound
      exclusively to a single 65- to 70-kDa protein in MA-RCC and U251 cells, while in
      TF-1 cells it cross-linked to two membrane proteins of 65 to 70 kDa and 140 kDa.
      Furthermore, by using a chimeric protein composed of IL-13 and Pseudomonas
      exotoxin A, we observed that IL-4 neutralized the cytotoxicity of the IL-13 toxin
      on COS-7 cells by blocking a common form of the two cytokine receptors. We
      propose that the 65- to 70-kDa form of the IL-13R is the predominant common
      component shared between IL-13 and IL-4R. However, the primary IL-4 binding
      (p140) protein also participates in the formation of the IL-13R complex in some
      cell types. In addition, the gamma(c) or another interactive subunit may
      influence IL-13 binding to its receptor complex. Thus, we propose that there are
      at least four forms of IL-13R.

PMID- 8992993
TI  - Identification of IL-4 promoter elements conferring Th2-restricted expression
      during T helper cell subset development.
AB  - Selective cytokine gene expression by T cell subsets underlies polarization of
      cellular and humoral immune responses. Our interest has been to define the
      molecular basis for restricted cytokine expression by Th1 and Th2 cells. IL-4 is
      selectively expressed by Th2 cells, providing a model for Th2-specific gene
      expression. To allow for promoter analysis during the process of Th1/Th2
      differentiation within a normal cellular context, we have taken a transgenic
      approach. We generated a series of murine transgenic lines harboring both the
      DO11.10 alphabeta-TCR transgene and the luciferase gene driven by regions of the
      IL-4 promoter. The results identify proximal promoter regions that provide
      significantly Th2-restricted IL-4 gene expression. The IL-4 -741- to +60-bp
      region allows, on the average, 40-fold higher inducible reporter activity in Th2
      cells than in Th1 cells. When trimerized, the region spanning -88 to -61 bp,
      containing a composite NF-AT/AP-1 site, also confers significant Th2-specific
      reporter activity. These results suggest that trans-acting factors binding this
      NF-AT/AP-1 composite site cooperate to allow substantial Th2-selective reporter
      expression. Finally, because reporter expression is low relative to endogenous IL
      4 mRNA in activated Th2 cells, we suggest that additional control elements
      outside of the IL-4 promoter may be required to enhance overall IL-4 gene
      activity.

PMID- 8992994
TI  - Infection of human vascular endothelial cells with Staphylococcus aureus induces
      hyperadhesiveness for human monocytes and granulocytes.
AB  - The consequences of internalization of Staphylococcus aureus by HUVEC with
      respect to their adhesiveness for human monocytes and granulocytes were
      investigated. Viable and UV-killed, but not heat-killed, S. aureus were
      internalized by HUVEC, which required participation of the endothelial
      cytoskeleton. S. aureus-infected HUVEC displayed increased surface expression of
      CD106 (VCAM-1), CD54 (ICAM-1), and MHC I molecules. Expression of CD62P (P
      selectin), CD62E (E-selectin), CD31 (PECAM-1), and CD102 (ICAM-2) was not
      affected. Concomitantly, these HUVEC expressed a time- and inoculum size
      dependent hyperadhesiveness for monocytes and granulocytes. Monocyte adhesion
      reached maximal levels (approximately 60% adhesion) 23 h after the initial 1 h
      period of infection of HUVEC with about 50 bacteria per single HUVEC. To induce
      maximal (approximately 20%) adhesion of granulocytes, five times higher
      concentrations of HUVEC-infecting bacteria were required. Using the appropriate
      mAb, granulocyte adhesion to S. aureus-infected HUVEC was shown to be entirely
      mediated by the beta2 (CD11/CD18) integrins. Monocyte adhesion to these HUVEC was
      largely (approximately 70%) dependent on both CD11a/CD18 (LFA-1) and CD49d/CD29
      (VLA-4). This demonstrates that infection of HUVEC with S. aureus potentiates
      CD11/CD18-mediated granulocyte adhesion and shifts the mechanism of monocyte
      adhesion from being completely CD11/CD18 dependent to one that also utilizes the
      VLA-4/VCAM-1 dependent pathway. Together, these findings indicate that in
      response to internalization of S. aureus, vascular endothelial cells may initiate
      recruitment of monocytes and granulocytes, which may be an important initial
      event in the pathogenesis of endovascular diseases.

PMID- 8992995
TI  - Rejection of a nonimmunogenic melanoma by vaccination with natural melanoma
      peptides on engineered antigen-presenting cells.
AB  - Naturally processed peptides, obtained by acid extraction of tumor cells, contain
      Ags able to activate specific CTL in vitro. We recently reported that the
      nonprofessional APC, RMA-S, expressing the B7.1 molecule (RMA-S/B7), pulsed with
      naturally processed peptides from the nonimmunogenic B16F1 melanoma (B16F1a.e.)
      primed syngenic CD8+ T cells against the tumor in vitro. Here, we show the
      rejection of B16F1 melanoma by C57BL/6 mice after immunization with RMA-S/B7
      cells pulsed with B16F1a.e. This response is critically dependent on both CD4+
      and CD8+ cells, but not on NK cells. However, only CD8+ T cells exert anti-B16F1
      cytolitic activity in vitro. Moreover, RMA-S/B7 cells pulsed with B16F1a.e. can
      be used to prevent the growth of 24-h preestablished melanomas. These results may
      have important implications for the clinical use of natural peptide fractions of
      tumor cells as therapeutic cancer vaccines.

PMID- 8992996
TI  - Effect of serum IgG1 to Cryptococcus neoformans glucuronoxylomannan on murine
      pulmonary infection.
AB  - Little is known about the role of Ab in protection against pulmonary fungal
      pathogens. The ability of murine IgG1 mAb 2H1 to modify pulmonary Cryptococcus
      neoformans infection was investigated in intratracheal infection. mAb 2H1 binds
      C. neoformans glucuronoxylomannan. mAb 2H1 was given to A/JCr mice 24 h before
      infection. Two C. neoformans strains were studied: ATCC 24067 (serotype D) and
      62070 (serotype A). Fungal burden was determined by CFU 14 days after infection
      for both strains, and at 2 h, 24 h, 48 h, 7 days, and 28 days after infection for
      strain 24067. On day 14, mAb 2H1 treatment reduced CFU in the lung, brain, and
      liver for strain 62070 infection. Minor reductions in lung CFU followed infection
      with strain 24067 in mAb 2H1-treated mice, despite prolonged survival. The
      limited ability of mAb 2H1 to reduce lung CFU may reflect rapid phagocytosis of
      yeast by alveolar macrophages, seen by electron microscopy 2 h after infection,
      regardless of whether mice had received mAb. Alveolar macrophages phagocytosed
      and reduced C. neoformans CFU in vitro only in the presence of mAb 2H1.
      Differences were apparent in phagocytosis and in vitro killing between strains
      24067 and 62070. Serum IgG1 modified the course of pulmonary infection in mice by
      prolonging survival, reducing CFU, and reducing tissue glucuronoxylomannan Ag.
      mAb administration was associated with enhanced granulomatous inflammation, but
      did not prevent infection or dissemination. Despite incomplete protection by
      serum Ab against pulmonary infection, our results provide encouragement for
      continued vaccine development.

PMID- 8992997
TI  - IL-15, an immunomodulator of T cell responses in intracellular infection.
AB  - IL-15 is a novel cytokine with potent T cell growth factor activity. Here, we
      investigated the role of IL-15 in the human immune response to intracellular
      infection by studying patients leprosy. We found that IL-15 mRNA and protein were
      more strongly expressed in immunologically resistant tuberculoid patients than in
      with unresponsive and susceptible lepromatous patients. In vitro, Mycobacterium
      leprae induced IL-15 secretion from peripheral blood monocytes. Furthermore, rIL
      15 by itself and in combination with rIL-2 or rIL-7 augmented PBMC proliferative
      responses to the pathogen. Although rIL-15 expanded the CD3-CD56+ (NK) subset,
      rIL-15 combined with M. leprae induced the expansion of CD3+CD56+ T cells.
      Immunohistologic analysis of leprosy skin lesions indicated that the frequency of
      CD56+ cells was greatest in the group of patients with high IL-15 expression, and
      that >90% of the CD56+ cells in lesions were CD3+ T cells. Therefore, IL-15
      augments the local T cell response to human intracellular pathogen.

PMID- 8992998
TI  - Antagonism of vaccine-induced HIV-1-specific CD4+ T cells by primary HIV-1
      infection: potential mechanism of vaccine failure.
AB  - Prior immunity to HIV-1 elicited by vaccination may modify subsequent responses
      upon exposure to infectious HIV-1. An HIV-1-uninfected person entered in a
      vaccine trial that included immunizations to HIV-1(LAI) envelope with a
      recombinant vaccinia vector and recombinant protein developed envelope-specific
      CD4+ T cell responses, including proliferative and cytolytic responses, but was
      not protected from a high risk HIV-1 exposure. CD4+ T cell clones derived from
      blood at the peak of vaccine-induced immunity recognized and lysed autologous
      target cells expressing four distinct regions within the HIV-1(LAI) envelope
      region; three of these CTL clones also recognized targets expressing envelope
      from a similar viral subtype, HIV-1(MN). The epitope specificity of CD4+ clone
      9G8, recognizing both HIV-1(LAI) and HIV-1(MN) envelope, was within the 571-590
      amino acid envelope region. Sequence analysis of the first infectious autologous
      strain revealed two amino acid mutations within this region. The 9G8 CTL clone
      induced by immunization failed to recognize targets expressing the corresponding
      CTL epitope from the infecting virus. Moreover, a peptide based on the epitope
      sequence of the infecting isolate antagonized the vaccine-induced CTL clone such
      that the CTL clone was no longer able to recognize the vaccine strain or HIV
      1(MN) epitope. These findings suggest a potentially novel mechanism associated
      with vaccine failure whereby the infecting virus may not only escape from CTL
      activity, but also alter the ability of CTL to recognize other variants in an
      individual.

PMID- 8992999
TI  - In vivo engineering of a cellular immune response by coadministration of IL-12
      expression vector with a DNA immunogen.
AB  - Recent studies support the importance of investigating a DNA vaccination approach
      for the immunologic control of HIV-1. In this regard, it may be important to
      specifically engineer immune responses in order to improve on first generation
      vaccine attempts. Especially for HIV, induction of cell-mediated immunity may be
      an important feature for any candidate vaccine. In an attempt to engineer in vivo
      the enhancement of cellular immune response and to direct Ag-dependent immune
      response from Th2 to Th1 type, we investigated the role of codelivery of genes
      for IL-12 and granulocyte-macrophage-CSF along with DNA vaccine formulations for
      HIV-1 Ag. We found that codelivery of IL-12 expression cassettes with DNA
      vaccines for HIV-1 in mice resulted in splenomegaly as well as a shift in the
      specific immune responses induced. The codelivery of IL-12 genes resulted in the
      reduction of specific Ab response, while the coinjection of granulocyte
      macrophage-CSF genes resulted in the enhancement of specific Ab response. In
      addition, we observed a significant Ag-specific stimulation of T cells with
      codelivery of both cytokines. Most importantly, we observed a dramatic increase
      in specific CTL response from the group coimmunized with the HIV-1 DNA vaccine
      and IL-12 genes. This work demonstrates the power of DNA delivery in vivo for
      both the production of a new generation of more effective and targeted vaccines
      or immunotherapies as well as an analytic tool for the molecular dissection of
      the mechanisms of immune function.

PMID- 8993000
TI  - IL-12 exacerbates helminth-mediated corneal pathology by augmenting inflammatory
      cell recruitment and chemokine expression.
AB  - Corneal inflammation (keratitis) is a major cause of visual impairment in
      Onchocerca volvulus infection. Previous studies showed that onchocercal keratitis
      can be induced in mice following s.c. immunization and intracorneal injection
      with soluble O. volvulus Ags (OvAg), and that the inflammatory response is
      dependent on T cells and IL-4. Since recombinant IL-12 impairs IL-4-dependent,
      Th2-mediated responses in other parasitic infections and in models of allergic
      asthma, the present study was undertaken to determine the effect of IL-12 on
      onchocercal keratitis. Mice were injected i.p. with IL-12 or saline at the time
      of initial sensitization to OvAg. Surprisingly, IL-12 treatment caused
      significant exacerbation of corneal pathology, which was associated with
      increased eosinophil and mononuclear cell infiltration into the corneal stroma.
      Consistent with the well-documented effect of IL-12 on Th1 cell development,
      corneas of IL-12-treated animals had elevated expression of the Th1 cytokine IFN
      gamma and diminished expression of the Th2 cytokines IL-4, IL-5, IL-10, and IL
      13. However, corneas from these animals also had marked elevation of alpha- and
      beta-chemokines known to be active on eosinophils and mononuclear cells,
      including IFN-gamma-inducible protein (IP)-10, macrophage inflammatory protein
      1alpha, macrophage inflammatory protein-1beta, JE/monocyte chemotactic protein-1,
      RANTES (regulated upon activation, normal T expressed and secreted), and eotaxin.
      Together, these data indicate that IL-12 exacerbates OvAg-mediated corneal
      pathology by enhancing chemokine expression and recruitment of inflammatory
      cells.

PMID- 8993002
TI  - Bispecific monoclonal antibody complexes bound to primate erythrocyte complement
      receptor 1 facilitate virus clearance in a monkey model.
AB  - We investigated the feasibility of using bispecific mAb complexes to redirect and
      improve the efficiency of the primate E complement receptor 1-based clearance
      reaction to remove a virus from the circulation. As an initial approach, we used
      bacteriophage phiX174 as an immunologic model for mammalian viruses. Bispecific
      complexes were prepared by chemically cross-linking a mAb specific for complement
      receptor 1 with a mAb specific for the bacteriophage phiX174. In a monkey model
      these complexes facilitate rapid and quantitative binding of the target
      bacteriophage to E in vitro and in vivo. Moreover, after in vivo binding to E,
      the complexes containing mAb and prototype virus are rapidly cleared from the
      circulation of rhesus and cynomolgus monkeys without loss of E. Our findings
      suggest that bispecific mAb complexes, in concert with primate E complement
      receptor 1, may have therapeutic utility in the treatment of diseases associated
      with blood-borne pathogens.

PMID- 8993001
TI  - Intranasal immunization with CTL epitope peptides from HIV-1 or ovalbumin and the
      mucosal adjuvant cholera toxin induces peptide-specific CTLs and protection
      against tumor development in vivo.
AB  - To evaluate the ability of mucosal immunization protocols using peptide
      immunogens to induce CTL responses, BALB/c and C57BL/6 mice were immunized
      intranasally (i.n.) with peptides corresponding to a known CTL epitope in HIV-1
      glycoprotein 120 or OVA, respectively, and the mucosal adjuvant cholera toxin
      (CT). Intranasal immunization of BALB/c mice with a 10- or 15-amino acid peptide
      corresponding to a CTL determinant in HIV-1 glycoprotein 120 and CT induced
      peptide-specific CTLs in spleen cells that persisted through 35 days after the
      last immunization. Intranasal immunization of C57BL/6 mice with the octameric OVA
      peptide and CT produced similar results with detectable peptide-specific CTL in
      both the cervical lymph node and spleen. To test whether CTL induced by i.n.
      immunization with OVA peptide and CT were functional in vivo, groups of C57BL/6
      mice were injected with E.G7-OVA tumor cells that express the OVA protein and
      monitored for tumor growth. Animals immunized i.n. with OVA and CT were protected
      against tumor development as efficiently as animals immunized by the potent CTL
      induction protocol of i.v. injection with OVA-pulsed dendritic cells. Intranasal
      immunization with peptides corresponding to known CTL epitopes and CT provides a
      noninvasive route of immunization for the induction of CTL responses in vivo.

PMID- 8993003
TI  - B7-negative versus B7-positive P815 tumor: differential requirements for priming
      of an antitumor immune response in lymph nodes.
AB  - Efficient T cell activation requires two synergistic but distinct signals derived
      from antigenic peptides presented by the MHC and from costimulatory molecules,
      particularly those belonging to the B7 family. Lack of B7-CD28 interaction may
      cause unresponsiveness of T cells to subsequent exposure to Ag. Nevertheless,
      immunization by some B7- tumors induces an antitumor immune response. We found
      that the immune response against two B7- tumors, the mouse P815 mastocytoma and
      the E7C3 melanoma, requires host-derived B7, since blockage of the B7-CD28
      interaction facilitates tumor growth and eliminates an antitumor response. B7
      costimulation is provided in the regional, tumor-draining lymph nodes for the
      induction of a primary CTL response against both B7+ tumor and B7- tumor.
      However, the induction of a CTL response to B7+ tumors and its clonal expansion
      may occur at tumor sites in addition to secondary lymphoid organs so as to
      generate more effective tumor immunity.

PMID- 8993004
TI  - Eosinophils transcribe and translate messenger RNA for inducible nitric oxide
      synthase.
AB  - Because of the involvement of nitric oxide (NO) in inflammatory states such as
      parasitic and hypersensitivity disorders and the fact that eosinophils are one of
      the cell types implicated, we asked whether eosinophils were able to express mRNA
      specific to inducible NO synthase (iNOS) and iNOS protein and to secrete nitric
      oxide. iNOS protein was detected on eosinophil preparations by
      immunocytochemistry using iNOS mAb. Expression of iNOS protein was also detected
      by immunoblotting in human purified eosinophils and an eosinophilic leukemia cell
      line, Eol-3. Nitrite production was detected in the supernatant of human
      eosinophils and Eol-3 cells cultured for 24 h, and was completely inhibited in
      the presence of the NOS inhibitor N-methylester-L-arginine. iNOS cDNA was
      obtained by reverse transcription-PCR. After subcloning, sequencing of the 259-bp
      fragment from three different human eosinophils cDNAs revealed 97% identity with
      macrophage/monocyte iNOS. Our studies describe for the first time the presence of
      iNOS on eosinophil and a putative new role for this cell in inflammatory states
      such as asthma and parasitic disease.

PMID- 8993005
TI  - Association of non-receptor protein tyrosine kinases with the Fc gamma RI/gamma
      chain complex in monocytic cells.
AB  - To characterize the functional macromolecular complex of the high affinity
      receptor for IgG (Fc gamma RI), we have undertaken the identification of the
      molecules associated with the ligand binding unit and its associated subunit,
      gamma-chain, in a monocyte cell line, U937. Comparison of the pattern of tyrosine
      phosphorylated proteins that coprecipitate with anti-Fc gamma RI or anti-gamma
      chain Abs after Fc gamma RI clustering suggests that, like other receptor
      systems, the different units of the receptor associate or recruit different
      elements of the signaling pathway. Syk associates preferentially with the gamma
      chain subunit and not with Fc gamma RI itself. This association is dependent on
      receptor clustering and correlates with gamma-chain phosphorylation. The Src
      kinase Lyn is also part of the receptor complex. Lyn associates with both units
      of the receptor, and this association is independent of receptor engagement;
      however, the level of tyrosine phosphorylation of the kinase increases after Fc
      gamma RI clustering. Association of a 35-kDa phosphoprotein with the binding unit
      was also observed after receptor clustering. We further found that after Fc gamma
      RI clustering, tyrosine-phosphorylated Syk associates with Lyn. These data
      suggest that several levels of interaction occur between these molecules or that
      different pools of tyrosine kinases become activated after Fc gamma RI
      clustering.

PMID- 8993006
TI  - Cytolytic and cytostatic properties of an anti-human Fc gammaRI (CD64) x
      epidermal growth factor bispecific fusion protein.
AB  - A bispecific fusion protein (H22-EGF) that binds simultaneously to the epidermal
      growth factor receptor (EGF-R) and to the high affinity receptor for the Fc
      portion of human IgG, Fc gammaRI (CD64), has been successfully constructed and
      expressed. For this construction, genomic DNA encoding the Fd fragment of
      humanized anti-Fc gammaRI mAb, H22, which binds Fc gammaRI at an epitope that is
      distinct from the Fc binding site, was fused to cDNA encoding human epidermal
      growth factor (EGF), a natural ligand for EGF-R. The resulting H22Fd-EGF
      expressing vector was transfected into a myeloma cell line that was transfected
      previously with a vector containing DNA encoding the H22 kappa-light chain. SDS
      PAGE analysis of purified H22-EGF demonstrated that the fusion protein was
      secreted predominantly as H22Fab'-EGF monomer (approximately 55 kDa), even though
      a free Cys residue exists in the hinge region of the H22 Fab' component. Using a
      novel bispecific flow cytometry-binding assay, we demonstrated that the purified
      bispecific fusion protein, H22-EGF, was able to bind simultaneously to soluble Fc
      gammaRI and EGF-R-expressing cells. H22-EGF inhibited the growth of EGF-R
      overexpressing tumor cells and mediated dose-dependent cytotoxicity of these
      cells in the presence of Fc gammaRI-bearing cytotoxic effector cells. These
      results suggest that this fusion protein may have therapeutic utility for EGF-R
      overexpressing malignancies.

PMID- 8993007
TI  - Human monocyte adhesion is modulated by endothelin B receptor-coupled nitric
      oxide release.
AB  - Human monocytes have the capacity to produce both endothelin 1 (ET-1) and nitric
      oxide (NO), yet the roles of these mediators in monocyte function remain unclear.
      The relationship of ET-1 and NO release to monocyte adhesion was explored using
      peripheral blood monocytes (PBM) and the human monocytic cell lines THP-1 and
      U937. Specific binding of 125I-labeled ET-1 to THP-1 was abrogated by
      pretreatment with the endothelin B (ET(B)) receptor antagonist, BQ-788, but not
      by the endothelin A (ET(A)) receptor antagonist, BQ-123, consistent with
      predominant ET(B) receptor expression. Direct measurement of NO with an
      amperometric probe demonstrated the production of nanomolar concentrations of NO
      by PBM and THP-1 cells upon treatment with ET-1, which was abrogated by BQ-788,
      but not BQ-123, pretreatment, suggesting functional coupling of ET(B) receptors
      to NO release. Indeed, the presence of ET(B) receptor mRNA transcripts was
      detected in THP-1 and is consistent with previous reports that have demonstrated
      functional coupling of ET(B) receptors to constitutive NO synthase activation. In
      contrast, U937 cells did not release NO in response to ET-1 treatment, and mRNA
      transcripts were not detected in these cells, consistent their failure to bind
      125I-labeled ET-1, as previously determined. Exposure of PBM to ET-1 markedly
      reduced the adhesion of these cells to human saphenous vein, whereas PBM adhesion
      in the presence of BQ-788 was restored to control levels. These data demonstrate
      that PBM interactions with the vascular wall can be reduced by autocrine
      production of NO and suggest that ET(B) receptors may attenuate monocyte activity
      at sites of inflammation.

PMID- 8993008
TI  - Mechanism of sustained E-selectin expression in cultured human dermal
      microvascular endothelial cells.
AB  - Persistent E-selectin expression has been proposed to be a unique property of
      dermal vascular endothelium that directs skin-specific homing of a subpopulation
      of circulating memory T cells. We compared the kinetics of E-selectin expression
      on cultured human dermal microvascular endothelial cells (HDMEC) with expression
      on HUVEC. Following treatment with TNF, E-selectin on HDMEC appears more slowly
      than on HUVEC (peak values 6-8 vs 4 h, respectively) and is sustained at
      significantly higher levels after 24 h. E-selectin mRNA, analyzed by S1 nuclease
      protection, consists of a single predominant transcript that follows a similarly
      transient time course in both cell types. Cell surface E-selectin is internalized
      more slowly on HDMEC than on HUVEC (t1/2 = 4.3 vs 1.6 h, respectively) as
      measured by serial FACS analyses in the presence of the protein synthesis
      inhibitor cycloheximide. In comparison, intercellular adhesion molecule-1 (ICAM
      1) expression is not measurably reduced by either cell type under the same
      conditions. HDMEC are similar to HUVEC in rates of pinocytosis or receptor
      mediated endocytosis. Pulse-chase analysis indicated that the degradative half
      life of E-selectin protein is greater in HDMEC than in HUVEC (1.9 vs 1.5 h,
      respectively). E-selectin internalization in microvascular endothelial cells (EC)
      from lung and subcutaneous fat is slow, like HDMEC, whereas internalization in
      large vessel EC from saphenous vein and aorta is rapid, like HUVEC. We conclude
      that HDMEC sustain higher levels of expression at 24 h by slower internalization
      and degradation of E-selectin protein and that this may be a general property of
      microvascular EC.

PMID- 8993009
TI  - An increase in intracellular cyclic AMP modulates nitric oxide production in IFN
      gamma-treated macrophages.
AB  - Macrophages treated with IFN-gamma alone are stimulated to produce nitric oxide.
      The level of nitric oxide production can be enhanced significantly when IFN-gamma
      treatment is combined with other agents (e.g., LPS, TNF-alpha, IL-2, etc.). We
      tested the hypothesis that cAMP plays a role in the IFN-gamma-induced activation
      of macrophages. Our experiments indicate that factors that increase the
      concentration of cAMP in the murine macrophage cell line ANA-1 can also enhance
      IFN-gamma-induced production of nitric oxide. PGE2 and cholera toxin increased
      the production of nitrite (an indicator of nitric oxide production) in IFN-gamma
      treated ANA-1 macrophages by at least twofold. These factors produced no increase
      in nitric oxide production in the absence of IFN-gamma treatment. The increase in
      nitric oxide production corresponded to an increase in the accumulation of nitric
      oxide synthase mRNA without a change in stability of mRNA. Dibutyryl cAMP and Sp
      cAMPs (a selective activator of cAMP-dependent protein kinase I and II) also
      increased nitric oxide production in IFN-gamma-treated macrophages. However, at
      very high concentrations (i.e., >100 microM), the stimulatory effect was
      decreased. These studies indicate that elevation of intracellular cAMP causes a
      dose-dependent, biphasic alteration of IFN-gamma-induced nitric oxide production
      in murine macrophages. Moreover, they suggest that agents that affect nitric
      oxide synthesis may do so via modulation of the cAMP second messenger system.

PMID- 8993010
TI  - Regulation of inducible nitric oxide synthase messenger RNA expression and nitric
      oxide production by lipopolysaccharide in vivo: the roles of macrophages,
      endogenous IFN-gamma, and TNF receptor-1-mediated signaling.
AB  - To evaluate potential roles for macrophages, IFN-gamma, and TNF receptor 1
      (TNFR1) in the regulation of LPS-induced inducible nitric oxide synthase (iNOS)
      mRNA expression, we used a model of macrophage depletion as well as IFN-gamma
      (GKO) and TNFR1 (TNFR1 -/-) knockout mice. LPS-induced iNOS mRNA in spleen was
      ablated in both macrophage-depleted and GKO mice. In livers of macrophage
      depleted mice, LPS-induced iNOS mRNA was reduced by 55 to 85%, with the most
      profound reductions detected 6 and 8 h after LPS injection. In GKO mice, peak
      iNOS mRNA expression in liver (3 h) was unaffected by the loss of endogenous IFN
      gamma. By 6 to 12 h after LPS challenge, however, hepatic LPS-induced iNOS mRNA
      and serum nitrate/nitrite levels were reduced substantially in GKO mice. Residual
      LPS-induced iNOS mRNA in livers of GKO mice was nearly ablated by macrophage
      depletion, indicating that induction of iNOS mRNA in liver requires both
      endogenous IFN-gamma and either macrophages and/or macrophage-derived factors.
      TNFR1-mediated signaling was involved in the induction of LPS-induced iNOS mRNA
      in liver at 3 and 6 h, but not in its maintenance at 8 h. Conversely, induction
      of iNOS mRNA in spleen by LPS was independent of TNFR1-mediated signaling. Our
      results indicate that macrophages and/or their secreted products, endogenous IFN
      gamma production, and TNFR1-mediated signaling play key roles in the in vivo
      regulation of iNOS mRNA expression and that the extent of their involvement is
      both time and organ specific.

PMID- 8993011
TI  - TNF translationally modulates the expression of G1 protein alpha(i2) subunits in
      human polymorphonuclear leukocytes.
AB  - Priming of polymorphonuclear leukocyte responses to chemoattractants by TNF plays
      an important role in host defenses and inflammatory responses. TNF-induced
      priming is associated with an 80% increase in the membrane density of G alpha(i2)
      protein that is coupled to chemoattractant receptors. The present study examines
      the hypothesis that TNF stimulates increased synthesis of alpha(i2). Within 10
      min of addition, TNF stimulated a significant increase in total cellular G
      alpha(i2), as determined by pertussis toxin-catalyzed ADP ribosylation, which was
      blocked by the translation inhibitor cycloheximide. Immunoprecipitation of
      biosynthetically labeled alpha(i2) showed that TNF increased alpha(i2) synthesis
      by about 20% at 10 min. Nuclear run-ons showed no change in alpha(i2) mRNA
      synthesis in TNF-treated cells; however, steady state alpha(i2) mRNA levels were
      reduced following a 10-min exposure to TNF. Pretreatment with cycloheximide
      prevented the TNF-induced reduction in steady state alpha(i2) mRNA levels.
      Therefore, TNF stimulates alpha(i2) protein synthesis and mRNA degradation in the
      same time frame as priming. The increased alpha(i2) synthesis results from
      increased translation, not transcription, of alpha(i2) mRNA. Simultaneous G
      alpha(i2) protein synthesis and mRNA degradation provide a mechanism by which TNF
      priming is associated with a rapid, self-limiting increase in G protein
      expression.

PMID- 8993012
TI  - Granulocyte-macrophage colony-stimulating factor regulates the functional
      adhesive state of very late antigen-4 expressed by eosinophils.
AB  - As very late antigen-4 (VLA-4) can exist in different functional states, we have
      sought to determine whether a cytokine expressed by inflamed endothelium (i.e.,
      granulocyte-macrophage CSF (GM-CSF)) could regulate the functional state of VLA-4
      expressed by eosinophils. Using a micropipette single cell adhesion assay able to
      measure the strength of adhesion forces, eosinophils exhibited low levels of
      basal adhesion to unstimulated endothelium (separation force, 0.022 +/- 0.003
      mdynes). In contrast, individual eosinophils bound to IL-1beta-stimulated
      endothelium (0.49 +/- 0.02 mdynes), TNF-stimulated endothelium (0.62 +/- 0.05
      mdynes), or IL-4-stimulated endothelium (0.11 +/- 0.01 mdynes) with increased
      avidity as assessed by separation force. Eosinophil binding to IL-4-stimulated
      endothelium was significantly inhibited by neutralizing Abs to either vascular
      cell adhesion molecule (VCAM) or VLA-4. The strength of eosinophil adhesion to
      VCAM (0.31 +/- 0.02 mdynes) or to connecting segment-1 (CS-1) (0.18 mdynes) was
      greater than the strength of eosinophil adhesion to unstimulated endothelium
      (0.02 mdynes), but was less than the strength of eosinophil adhesion to IL-1beta
      stimulated endothelium (0.49 +/- 0.02 mdynes). After incubating eosinophils for
      30 min with GM-CSF, the mean adhesion strength of eosinophils to CS-1 and VCAM
      increased significantly by 84 and 54%, respectively, compared with that of
      controls. This increased binding of eosinophils to VCAM or CS-1 was not due to
      alterations in VLA-4 receptor number (assessed by FACS analysis) or alterations
      in VLA-4 receptor distribution (assessed by confocal microscopy). These studies
      suggest that endothelial-derived cytokines such as GM-CSF have the potential to
      alter the functional state of eosinophil-expressed VLA-4 from a low affinity
      state to a high affinity state.

PMID- 8993013
TI  - The neuronal glycoprotein telencephalin is a cellular ligand for the CD11a/CD18
      leukocyte integrin.
AB  - Many leukocyte functions depend on interactions between the leukocyte-specific
      beta2 integrins CD11/CD18 and their ligands, the intercellular adhesion molecules
      (ICAMs). Telencephalin (TLN) is a novel member of the Ig superfamily expressed in
      the central nervous system. The NH2-terminal five Ig-like domains of TLN show the
      highest homology with the Ig domains of ICAM-1, ICAM-2, ICAM-3, and LW (ICAM-4),
      the known cellular ligands for CD11a/CD18. Here, we demonstrate that TLN
      interacts with CD11a/CD18. Peripheral blood T cells, Jurkat T cells, and B
      lymphoblastoid cells bound to immunopurified recombinant human TLN proteins. This
      adhesion was through CD11a/CD18 and was significantly inhibited by an Ab to
      CD11a/CD18. Reciprocally, TLN-transfected L cells also bound to purified
      CD11a/CD18. Recombinant TLN proteins comprising either the first five Ig domains
      (TLN(1-5)) or the entire extracellular portion (TLN(1-9)) showed binding to
      CD11a/CD18. We conclude that TLN is a novel neuronal cell adhesion molecule that
      may be important in integrin-mediated cell-cell interactions in the central
      nervous system, and that the CD11a/CD18-dependent recognition site of human TLN
      is located within the NH2-terminal five domains of this molecule.

PMID- 8993014
TI  - The human complement C1 complex has a picomolar dissociation constant at room
      temperature.
AB  - Periodic sampling of serum or reconstituted C1 initially diluted 1/2000 and
      1/4000 (that is, to 0.1 and 0.05 nM) into a recombinant C1s-containing solution
      showed a gradual decline of hemolytic activity until equilibrium was approached,
      consistent with a simple dissociation, reassociation equilibrium, presumably C1 <
      -> C1q + C1r2C1s2. The presence of excess (5 nM) recombinant C1s minimized
      further dissociation of the C1r2C1s2, allowing the first step to be studied
      independently of the dissociation of C1r2C1s2 <--> C1r2 + 2 C1s. Reassociation
      experiments were also performed, starting with the dissociated C1 diluted to the
      same concentrations and following the regain of hemolytic activity to
      approximately the same values, showing that the same equilibrium had been
      achieved from both directions. Analysis of the kinetic data yielded forward and
      reverse rate constants and the equilibrium constant, for which values of
      approximately 72 and 3 pM were estimated at 0 and 23 degrees C, respectively. The
      effects of temperature, ionic strength, Ca2+ ion concentration, and activation of
      the zymogen on the equilibrium constants were explored; extreme sensitivity to
      temperature, ionic strength, and activation were found. At 23 and 30 degrees C,
      slow activation of C1 was also evident. Highly purified, reconstituted C1 yielded
      approximately the same values for the kinetic and equilibrium parameters as serum
      C1, suggesting that the structure of the reconstituted complex was similar to or
      identical with that of the serum C1 complex.

PMID- 8993015
TI  - Neutrophil apoptosis is modulated by endothelial transmigration and adhesion
      molecule engagement.
AB  - Termination of a neutrophil-mediated inflammatory response occurs through the
      activation of the endogenous cell death program, apoptosis. Neutrophil apoptosis
      is a constitutive process that can be accelerated or delayed by signals from the
      microenvironment. Since cellular localization at the site of an inflammatory
      challenge is the critical first step in a neutrophil response, we investigated
      the effects of neutrophil transendothelial transmigration on the kinetic
      expression of apoptosis. Neutrophils isolated from rat lung following challenge
      with LPS demonstrated a significant delay in spontaneous apoptosis. This delay
      was a consequence of transmigration, since a comparable delay was seen when TNF
      alpha, a potent inducer of apoptosis in vitro, was used as the inflammatory
      stimulus. Human neutrophils demonstrated comparable delays in apoptosis in vitro
      following migration across an endothelial monolayer in response to FMLP. Delayed
      apoptosis only occurred in cells that had first been primed by LPS, a stimulus
      shown to up-regulate beta2 integrins and down-regulate L-selectin. Finally,
      crosslinking of CD11a or CD11b, but not of CD18, with mAbs and F(ab')2 fragments
      produced a delay in spontaneous apoptosis, whereas crosslinking of L-selectin
      with mAb or its natural ligand, sulfatides, accelerated the apoptotic process.
      Cells in which apoptosis was inhibited demonstrated persistent functional
      respiratory burst activity. These observations establish a role for endothelial
      transmigration in the regulation of neutrophil apoptosis, and suggest that
      adhesion molecules serve a modulatory role in the expression of neutrophil
      programmed cell death.

PMID- 8993016
TI  - TNF-alpha-mediated lung cytokine networking and eosinophil recruitment in
      pulmonary fibrosis.
AB  - Despite abundant evidence documenting the importance of TNF-alpha in the
      pathogenesis of pulmonary fibrosis, its actual role has not been fully
      elucidated. Recent observations also indicate that eosinophils found in fibrotic
      lung express elevated levels of cytokines known to be important in lung fibrosis.
      These findings suggest a possible role for TNF-alpha in eosinophil recruitment
      and cytokine expression in this disease. To examine this hypothesis, pulmonary
      fibrosis was induced in mice by endotracheal bleomycin treatment, and separate
      groups of animals were also treated with either anti-TNF-alpha Ab or control
      serum. On days 7 and 14 post-bleomycin treatment, lungs were harvested and
      analyzed for fibrosis, cytokine expression, and eosinophil influx. Anti-TNF-alpha
      caused a significant reduction in lung fibrosis, as indicated by a reduction in
      hydroxyproline content, which was accompanied by suppression of lung TGF-beta1,
      IL-5, and JE mRNA expression. Examination of tissue sections revealed a
      significant reduction in lung eosinophils and overall cellularity by anti-TNF
      alpha treatment without a significant effect on the number of lung macrophages.
      The number of IL-5-expressing cells was also significantly reduced by anti-TNF
      alpha treatment. Since IL-5 is important in eosinophil differentiation,
      activation, and recruitment, these findings suggest a novel mechanism by which
      TNF-alpha could mediate pulmonary fibrosis via induction of IL-5-mediated
      eosinophil recruitment and fibrogenic cytokine production. Since these eosinophil
      derived cytokines include JE/monocyte chemotactic factor-1 and TGF-beta1, this
      cytokine networking orchestrated by TNF-alpha could, in turn, amplify the
      inflammatory response and drive the progression to fibrosis and end-stage lung
      disease.

PMID- 8993017
TI  - T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum
      of patients with peptic ulcer disease.
AB  - Chronic antral gastritis following Helicobacter pylori (Hp) infection is
      characterized by a cellular inflammatory infiltrate whose cytokines may represent
      a host-dependent factor influencing the outcome of the infection. The pattern of
      cytokines produced by the immunologically active cells in the gastric antrum was
      analyzed at the mRNA level in antral biopsies from five Hp-infected patients with
      duodenal ulcer and three Hp-negative dyspeptic controls. T cell clones were
      generated from parallel antral biopsies of the same Hp-infected patients and
      assessed for reactivity to Hp Ags, cytokine profile, and effector functions.
      Antral biopsies from all Hp-infected patients showed IFN-gamma, TNF-alpha, and IL
      12, but not IL-4, mRNA expression, whereas no cytokine mRNA signal was found in
      the mucosa of controls. A total of 24 out of the 163 CD4+ T cell clones (15%)
      derived from Hp-infected patients proliferated in response to a Hp lysate; 11
      clones (46%) also reacted with Cag-A, 2 with Vac-A, and 1 with urease. Upon Ag
      stimulation, 20 out of the 24 Hp-reactive clones (83%) produced IFN-gamma, but
      not IL-4 or IL-5 (Th1-like), whereas 4 produced IFN-gamma, IL-4, and IL-5 (Th0
      like). All Hp-specific clones secreted high levels of TNF-alpha. At low T:B cell
      ratio, Hp-specific clones expressed Ag-dependent helper function for B cell
      proliferation and Ig production, whereas at higher T:B cell ratios, 15 Th1 and 2
      Th0 clones lysed Ag-pulsed autologous EBV-transformed B cells. Results provide
      evidence for Hp-specific Th1 effectors in the gastric antrum of Hp-infected
      patients, where they may play a role in the genesis of either peptic ulcer or Hp
      associated gastric B cell lymphoma.

PMID- 8993018
TI  - Structural and affinity studies of IgM polyreactive natural autoantibodies.
AB  - Natural polyreactive autoantibodies (NAA) are an important component of the
      normal B cell repertoire. One intriguing characteristic of these Abs is their
      binding to various dissimilar Ags. It has been generally assumed that these Abs
      bind the Ags with low affinity, and are encoded by germline genes. We have used
      surface plasmon resonance to determine binding of avidities, and conducted a
      structural analysis of five murine monoclonal natural autoantibodies displaying a
      typical polyreactive binding pattern against cytoskeleton Ags and DNA. We show
      that 1) all the five Abs bind the different Ags with kinetic constants similar to
      those observed for immune Abs; 2) they express a restricted set of V(H) and V(L)
      genes, since the same V(H) gene is expressed by three out of the five, and one
      particular Vkappa gene was expressed twice. In addition, a single D gene segment
      was used by three of the five Abs; and 3) they express, in most cases, genes in a
      close germline configuration. Our amino acid sequence and modeling studies show
      that the distribution of exposed side chains in the NAA paratopes is close to the
      general pattern observed in the complementarity-determining regions (CDRs) of
      variable domains from immune Abs. Although CDR3 regions of the heavy chain have
      been postulated to play a major role in determining polyreactivity on the basis
      of recombinatorial experiments, our results failed to show any distinctive
      particularity of this region in terms of length or charge when compared with
      classical immune Abs.

PMID- 8993019
TI  - Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X
      linked immunodeficiency with hyper-IgM.
AB  - We report an association between X-linked immunodeficiency with hyper-IgM (XHIM)
      and carcinomas affecting the liver, pancreas, biliary tree, and associated
      neuroectodermal endocrine cells. The tumors were fatal in eight of nine cases and
      in most instances were preceded by chronic cholangiopathy and/or cirrhosis. An
      additional group of subjects with XHIM had chronic inflammation of the liver or
      bile ducts but no malignancy. Many patients with XHIM were infected with
      cryptosporidia. CD40 is normally expressed on regenerating or inflammed bile duct
      epithelium. A CD40+ hepatocellular carcinoma cell line, HepG2, susceptible to
      cryptosporidia and CMV infection became resistant when cell surface CD40 was
      cross-linked by a CD40 ligand fusion protein. Apoptosis was triggered in HepG2
      cells if protein synthesis was blocked by cycloheximide or if the cells were
      infected by cryptosporidia. Ligation of CD40 on biliary epithelium may contribute
      to defense against infection by intracellular pathogens. We propose that the CD40
      ligand mutations that cause XHIM deprive the biliary epithelium of one line of
      defense against intracellular pathogens and that malignant transformation in the
      biliary tree follows chronic infection or inflammation. The resulting tumors may
      then progress without check by an effective immune response. Patients with XHIM
      who have abnormal liver function tests should be considered at increased risk for
      cholangiopathy or malignancy.

PMID- 8993021
TI  - Mapping of a gene for the increased susceptibility of B1 cells to Mott cell
      formation in murine autoimmune disease.
AB  - Mott cells, a pathologic state of plasma cells containing intracellular
      inclusions of Igs (Russell bodies), are frequent in lymphoid tissues of murine
      and human autoimmune diseases. However, neither the genesis nor the significance
      of Mott cells in autoimmune diseases is well understood. We found that B1, but
      not B2, cells were induced in vitro to form Mott cells in the presence of LPS or
      IL-5, but not other stimulants, in a much higher frequency in autoimmune New
      Zealand Black (NZB) and NZB x New Zealand White (NZB/W) F1 than in non-autoimmune
      disease-prone mice and notably athymic nude NZB/W F1 mice. Cell surface
      phenotypes of Mott cells were B220+ CD5+ CD43+ CD11b(dull), while those of
      peritoneal macrophages were B220- CD5- CD43(dull) CD11b+. We mapped a locus
      (provisionally designated Mott-1) controlling Mott cell formation that was
      tightly linked to microsatellite marker loci, D4 Mit70 and D4 Mit48, of
      autoimmune NZB mice, which is in close proximity to our recently mapped locus Imh
      1 for hypergammaglobulinemia. This region contains candidate genes that may be
      relevant to the aberrant B cell activation and differentiation. We suggest that
      while the Mott cell by itself is not the effector for autoimmune disease, the
      genetically determined aberrant maturational process of B1 cells that underlies
      the pathogenesis of autoimmune disease forms the basis for Mott cell formation in
      a T cell-dependent manner.

PMID- 8993020
TI  - CD28/B7 costimulation regulates autoimmune diabetes induced with multiple low
      doses of streptozotocin.
AB  - Insulin-dependent diabetes mellitus is believed to occur as a result of a T cell
      mediated destruction of the islets of Langerhans. The factors that regulate the T
      cell responses, in particular the costimulatory signals required for the T cell
      activation, which result in islet cell destruction, are still unclear. CD28/B7
      interactions have been shown to be important in the regulation of T cell immune
      responses. We, therefore, have examined the role of CD28/B7 interactions in a
      model of insulin-dependent diabetes mellitus in which T cell-dependent insulitis
      and hyperglycemia occur over a brief period, following multiple low doses of
      streptozotocin (multidose streptozotocin (STZ)-induced diabetes mellitus).
      Expression of CD28 was necessary for diabetes because CD28 -/- C57BL/KsJ animals
      developed neither hyperglycemia nor insulitis, and did not express IFN-gamma mRNA
      following STZ, unlike CD28 +/- C57BL/KsJ mice. The expression of B7-1 (CD80) and
      B7-2 (CD86) molecules was closely regulated during development of the disease.
      Expression of both CD80 and CD86 increased on cells in pancreatic lymph nodes in
      STZ-treated C57BL/KsJ mice. Expression of only CD86 increased on islet cells in
      diabetic mice. In wild-type animals, treatment with mAb against CD86 prevented,
      whereas treatment with mAb against CD80 exacerbated, insulitis and hyperglycemia,
      indicating that mAbs against these molecules differentially affect development of
      disease. We conclude that CD28 signal transduction is required for development of
      diabetes in multidose STZ-induced diabetes mellitus. CD80 and CD86 molecules, the
      CD28/CTLA4 ligands, may have different roles in regulation of the disease and
      affect T cell function at steps beyond differentiation into mature phenotypes.

PMID- 8993022
TI  - Successful formation of a chimeric human thymus allograft following
      transplantation of cultured postnatal human thymus.
AB  - Transplantation of cultured postnatal human thymus was performed in a patient
      with complete DiGeorge syndrome. Biopsy of the graft 3 mo after implantation
      revealed normal CD1+ thymocytes in thymic cortical epithelial regions and CD1-
      thymocytes in thymic medullary epithelial regions, respectively. HLA analysis of
      graft thymocyte and thymic microenvironment components demonstrated that
      developing thymocytes and thymic macrophages were recipient derived, while thymic
      epithelial components were of donor origin. The patient, who initially had no T
      cells and had profoundly defective T cell function, developed normal T cell
      responses to mitogens and Ags, tolerance to donor in a mixed lymphocyte reaction,
      and normal Ab titers after tetanus toxoid and pneumovax immunization. Thus,
      transplantation of cultured postnatal human thymic tissue in humans can form
      functional chimeric thymic tissue, and may provide a strategy to reconstitute the
      peripheral T cell pool in select congenital and acquired immune deficiency
      syndromes.

PMID- 8993023
TI  - Reversal of 1,3-bis(2-chloroethyl)-1-nitrosourea-induced severe immunodeficiency
      by transduction of murine long-lived hemopoietic progenitor cells using O6
      methylguanine DNA methyltransferase complementary DNA.
AB  - Bone marrow toxicity is a dose-limiting side effect of chloroethylnitrosourea
      (CNU) chemotherapeutic alkylating agents. A major determinant of CNU cytotoxicity
      is the methylation of guanine at the O6-position and the subsequent formation of
      interstrand DNA cross-links. O6-Methylguanine DNA methyltransferase (MGMT)
      removes alkyl groups from the O6 position of guanine and has been shown to repair
      CNU-induced DNA damage. We have previously demonstrated that transplantation of
      murine bone marrow cells transduced with a recombinant retroviral vector
      expressing MGMT via the human phosphoglycerate kinase promoter (PGK-MGMT)
      protects animals in vivo from acute myelotoxicity associated with CNU treatment.
      In the present study, we examined the effects of 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU), a commonly used CNU, on long term recovery of the lymphoid
      compartment, including thymus reconstitution, peripheral T and B cell
      populations, and lymphocyte mitogen responses in mice reconstituted with PGK-MGMT
      transduced hemopoietic cells. Mice transplanted with either mock-infected control
      or PGK-MGMT-transduced stem cells were treated with five weekly doses of BCNU.
      Analysis of the lymphoid compartment demonstrated significant damage 3 mo after
      the last BCNU dose in control animals. In contrast, the profound deficiency in
      CD4+CD8+ double-positive thymocytes and mature lymphocytes observed in control
      mice surviving BCNU treatment was completely reversed in mice transplanted with
      PGK-MGMT-transduced bone marrow and was associated with molecular evidence of in
      vivo selection of transduced cells in the lymphoid compartment. Thus, long term
      immunodeficiency following CNU therapy may be prevented by genetic modification
      of murine hemopoietic stem cells with MGMT, leading to significant improvement in
      post-transplant immune function.

PMID- 8993024
TI  - Dual role of HIV Tat in regulation of apoptosis in T cells.
AB  - Apoptosis has been suggested to be one of the major mechanisms of depletion of
      CD4+ T cells in HIV-1-infected individuals. Remarkably, HIV-1-infected cells
      appear protected from apoptosis, whereas bystander cells show increased apoptosis
      in lymph nodes of infected individuals. In this work, we present evidence that
      the trans-activating protein of HIV-1, Tat, has a dual role in regulation of
      apoptosis in T cells. While addition of exogenous Tat protein induced apoptosis
      in uninfected T cells, T cell clones stably expressing the Tat protein were
      protected from activation-induced apoptosis. The addition of exogenous Tat
      potentiated anti-CD3 mAb, anti-Fas IgM mAb, and TNF-alpha-induced apoptosis of T
      cells. Pretreatment of Tat with anti-Tat Ab abrogated Tat-induced apoptosis, but
      did not affect anti-Fas IgM Ab-induced apoptosis. Endogenously expressed Tat was
      analyzed in Jurkat T cell clones transfected with either full-length tat gene
      (101 amino acids), or in control cells containing an empty vector. The Tat101
      transfected clones were resistant to anti-CD3-induced apoptosis, when compared
      with cells transfected with vector alone. Furthermore, cross-linking of CD4
      molecules on T cells with gp160 and anti-gp160 Ab showed markedly decreased
      apoptosis in Tat101 cells compared with that induced in cells transfected with
      vector alone. Taken together, our results indicate that HIV-1 Tat can regulate
      apoptosis that may contribute to the immunopathogenesis of AIDS.

PMID- 8993025
TI  - TCR in Fas-sensitive T cells from labial salivary glands of patients with
      Sjogren's syndrome.
AB  - Apoptosis is found in labial salivary glands of patients with Sjogren's syndrome
      (SS). To analyze the pathogenesis of apoptosis in labial salivary glands of SS
      patients, we examined the expression of Fas Ag and Fas ligand (FasL) and TCR on T
      cells susceptible to anti-Fas mAbs (CH-11). Fas Ag is expressed on epithelial
      cells and mononuclear cells in the salivary glands as observed by an
      immunohistochemical method. FasL is over-expressed specifically on T cells
      infiltrating into the labial salivary glands as seen by an reverse transcription
      PCR method. These results suggest that apoptosis in SS lips is mediated by a
      Fas/FasL pathway. PCR single-strand conformation polymorphism (SSCP) clearly
      demonstrated that more than 40% of the T cells accumulated in labial salivary
      glands are deleted by incubation with CH-11 for 24 h in vitro, indicating that
      these expanded cells are Fas sensitive. junctional sequence analysis showed that
      the same conserved amino acid motifs (LAGG, RLA, SLG, QGPG, PGG, GGE, RGR, KPG,
      AGD, and MLG) in complementarity determining region 3 (CDR3) are found in Fas
      sensitive T cell clones, whereas they are not detected in Fas-resistant clones,
      suggesting that Fas-sensitive T cells recognize restricted T cell epitopes on
      autoantigens. In conclusion, the findings suggest that Fas-sensitive T cells in
      labial salivary glands of SS patients are generated by Ag stimulation and might
      function as autoreactive T cells.

PMID- 8993026
TI  - Identifying specific protein-DNA interactions within living cells, or in "in vivo
      footprinting".

PMID- 8993027
TI  - In vivo footprinting of the interaction of proteins with DNA and RNA.
AB  - Analysis of the interaction of proteins with either DNA or RNA sequences by in
      vivo footprinting involves two steps: (i) the in situ modification of nucleic
      acids by the footprinting reagent and (ii) the visualization of the footprints.
      Ligation-mediated PCR (LM-PCR) procedures provide a level of sensitivity and
      specificity that is suitable for visualization of footprints of single-copy genes
      or low-abundance mRNAs in higher eukaryotes. In this article, we discuss several
      of the technical aspects of these multistep procedures that contribute to the
      quality of the results, particularly the parameters that affect the specificity
      and fidelity of the reactions: (i) the design of the primers, which is important
      to achieve optimal specificity; (ii) the choice of polymerases so that the
      amplified material represents faithfully the initial nucleic acid population; and
      (iii) the impact of the plateau effect within the PCR on the interpretation of
      the data. We then discuss aspects of in vivo nucleic acid manipulation that may
      affect the quality of the footprinting image, in particular the choice of the
      footprinting reagent and its condition of use (e.g., on intact or permeabilized
      cells or prepared nuclei) and the extent of nucleic acid modification. Finally,
      we provide detailed experimental procedures corresponding to the techniques we
      have developed or modified: LM-PCR, reverse ligation-mediated PCR, and nuclease
      treatment of RNAs in vivo.

PMID- 8993028
TI  - Guanine-adenine ligation-mediated PCR in vivo footprinting.
AB  - The identification of relevant DNA regulatory sequences involved in
      transcriptional control is critical to establishing which proteins mediate cell
      specific gene expression. As an approach to investigating the mechanisms of gene
      regulation, in vivo footprinting studies reveal protein-DNA interactions as they
      actually occur in situ. We have used in vivo footprinting to complement in vitro
      studies of the human globin locus control regions (LCRs) in erythroid cells. To
      further enhance the detection of protein contacts with this technique, we have
      modified the dimethyl sulfate-based ligation-mediated PCR (LMPCR) in vivo
      footprinting procedure to permit the assessment of protein binding at guanine and
      adenine residues, rather than exclusively at guanines. This modification, termed
      GA-LMPCR in vivo footprinting, was essential for the analysis of GATA-1 motifs in
      the alpha-LCR and HS-3 of the beta-LCR. Moreover, GA-LMPCR in vivo footprinting
      provided high-resolution analysis of AP-1/NF-E2 elements and revealed protein
      contacts at sequences that are not coincident with previously described
      regulatory motifs. A comprehensive discussion of the GA-LMPCR in vivo
      footprinting methodology and representative analyses from our studies, including
      GATA-1 and AP-1/NF-E2 motifs, are presented to illustrate the modified technique.

PMID- 8993029
TI  - Genomic footprinting of Drosophila embryo nuclei by linker tag selection LM-PCR.
AB  - The unmatched power of Drosophila genetics revealed the complex regulatory
      network of gene activities that governs the development of higher eukaryotes. An
      understanding of gene control at the level of transcription requires insight into
      the protein/DNA interactions that regulate transcription in the developing
      embryo. Genomic footprinting allows the direct visualization of these protein/DNA
      interactions within intact nuclei or cells. In combination with other in vivo
      assays such as protein/DNA crosslinking and classical biochemistry, genomic
      footprinting can give valuable insight into the architecture of promoters in
      various states of activity. In this article we summarize our experience in
      analyzing Drosophila embryos by genomic footprinting and describe modifications
      of the ligation-mediated PCR procedure that have improved this analysis.
      Applications of genomic footprinting to embryos are currently limited by the fact
      that all target nuclei must be uniform with respect to the protein/DNA
      interactions at the chosen site. We discuss strategies that should allow the
      analysis of small numbers of cells derived from heterogeneous populations and
      tissues.

PMID- 8993030
TI  - In vivo footprinting with limiting amounts of embryo tissues: a role for C/EBP
      beta in early hepatic development.
AB  - Regulatory factors important for the developmental control of genes have been
      identified by genetic studies or by examining the ontological expression profiles
      of proteins that were originally characterized in adult tissues; direct
      biochemical studies of transcription factors within small amounts of embryo
      tissues have been limited. We have found that the ligation-mediated PCR (LM-PCR)
      technique can detect specific dimethylsulfate modifications in genomic DNA from
      as few as several thousand cells, making it technically feasible to identify
      protein-DNA interactions in pools of nascent embryo tissues. Herein we show that
      LM-PCR can reveal methylation protections on the albumin gene enhancer in
      embryonic mouse hepatocytes, indicating occupancy of a C/EBP factor binding site.
      Comparison of the in vivo protection pattern with that obtained from the in vitro
      analysis of different C/EBP isoforms suggests that in embryonic hepatocytes,
      C/EBP beta is bound to the albumin gene enhancer. Detailed protocols are provided
      so that the approach can be used to study other genes in developing embryos.

PMID- 8993031
TI  - Footprinting with UV irradiation and LMPCR.
AB  - Protein-DNA interactions in mammalian cells can be analyzed at the nucleotide
      level of resolution by genomic sequencing techniques. The most sensitive genomic
      sequencing method uses ligation-mediated polymerase chain reaction (LMPCR) for
      signal amplification. Several footprinting methods are compatible with LMPCR.
      Here we describe in detail the use of UV irradiation for in vivo footprinting.
      The distribution of the two major types of UV-induced DNA photoproducts
      [cyclobutane pyrimidine dimers and (6-4) photoproducts] can be analyzed by LMPCR
      and a wide variety of protein-DNA contacts can be detected by analyzing both
      photoproducts. A comparison of UV photofootprinting data with data from
      experiments using other probing techniques shows that UV light has the potential
      to reveal all protein-DNA interactions provided that there is a dipyrimidine
      sequence on either DNA strand within a factor binding site. The simplicity and
      nondisruptiveness of this probing method together with its ability to detect a
      large number of different transcription factors should make UV light a generally
      useful tool for in vivo footprinting. We provide protocols for UV footprinting
      and LMPCR.

PMID- 8993032
TI  - Genomic footprinting of retinoic acid regulated promoters in embryonal carcinoma
      cells.
AB  - Retinoic acid (RA) treatment of embryonal carcinoma (EC) cells initiates a
      cascade of alterations in gene regulation, leading to their differentiation into
      various cell types. In P19 EC cells RA treatment stimulates induction of the RAR
      beta gene, while it represses Oct3/4 gene expression. Here we present
      dimethylsulfate-based genomic footprinting analyses of these two genes. We found
      that the RAR beta promoter is not occupied prior to RA treatment, but following
      RA treatment all regulatory elements in this promoter become occupied. On the
      other hand, the Oct3/4 promoter is occupied at all three known elements before RA
      treatment, but this occupancy is coordinately lost following the treatment. Thus,
      factor occupancy coincides with expression of the genes. It is likely that the
      presence of factor binding or its absence revealed here represents a mechanism of
      the regulated expression of these genes in vivo. Our results demonstrate the
      power of genomic footprinting for studying regulatory events for transcription in
      vivo. In contrast, with in vitro protein-DNA binding assay, factors for both
      promoters are present in these cells regardless of RA treatment. It has been
      shown that RA receptor (RAR) and retinoid X receptor (RXR), by
      heterodimerization, mediate the RA action in EC cells. To elucidate the role of
      RAR/RXR heterodimers in the RAR beta promoter occupancy in vivo, genomic
      footprinting has been performed in P19 cells stably expressing dominant negative
      mutants of RXR. Two such mutants, lacking either the DNA binding domain or the C
      terminal activation domain, inhibit RA induction of the RAR beta gene in these
      cells. RA-induced factor occupancy is also markedly inhibited at all elements in
      the RAR beta promoter in these cells. Our results show that binding of liganded
      RAR/RXR heterodimers to RARE is required for other factors to gain access to
      their respective elements in the promoter.

PMID- 8993033
TI  - Analysis of chromatin structure by in vivo formaldehyde cross-linking.
AB  - Recent advances leave no doubt that higher order chromatin structures play a
      fundamental role in many developmentally important mechanisms of gene regulation.
      In particular analyses in genetic model systems like yeast and Drosophila
      uncovered novel proteins that are involved in the regulation of chromatin
      structures. Many of these proteins do not bind directly to DNA but interact in
      large multimeric complexes. To identify the DNA elements regulated by these
      multiprotein complexes, alternative approaches to the standard methods of DNA
      protein analysis had to be devised. Here we present a method that preserves the
      architecture of the higher order chromatin structures by cross-linking cells in
      vivo with formaldehyde. An immunoprecipitation strategy is then used to identify
      the DNA targets of chromosomal proteins of interest. This method can be applied
      to study the distribution of proteins at high resolution over extended
      chromosomal regions.

PMID- 8993034
TI  - Measurement of in vivo DNA binding by sequence-specific transcription factors
      using UV cross-linking.
AB  - This paper describes an in vivo UV cross-linking protocol that is sensitive
      enough to detect DNA binding by sequence-specific transcription factors in
      Drosophila embryos and tissue culture cells. The strength of this approach is
      that it provides a quantitative measure of DNA binding in vivo with unambiguous
      identification of the factor involved in the binding. This assay often detects
      DNA binding properties of proteins that were not predicted from previous
      experiments, and it can be used to directly test diverse models of gene
      regulation in the context of a living organism.

PMID- 8993035
TI  - UV-laser crosslinking of proteins to DNA.
AB  - Photochemical crosslinking is now a powerful method for studying protein-nucleic
      acid interactions. UV light is a zero-length crosslinking agent that
      predominantly or exclusively crosslinks proteins to nucleic acids at their
      contact points. It can therefore provide strong evidence for close protein
      nucleic acid interactions. However, to achieve an acceptable degree of
      crosslinking with conventional UV light sources, exposure times ranging from
      minutes to several hours are necessary. Such prolonged irradiation allows for the
      artifactual redistribution of proteins and precludes kinetic studies. The use of
      UV lasers overcomes these difficulties since the number of photons required for
      the crosslinking may be delivered in time intervals on the order of nano- or even
      picoseconds. We described detailed procedures for UV laser-induced protein-DNA
      crosslinking both in vivo and in vitro. Technical aspects, including the choice
      of UV laser for irradiation, the isolation of covalently crosslinked protein-DNA
      complexes, immunochemical techniques for both the identification and isolation of
      specific protein-DNA complexes and the identification of the crosslinked DNA
      sequences, are reviewed in detail. The application of UV laser crosslinking in
      kinetic studies is illustrated by the example of the TATA-binding protein (TBP)
      interaction with the adenovirus E4 promoter.

PMID- 8993036
TI  - Visualization of multicomponent transcription factor complexes on chromatin and
      nonnucleosomal templates in vivo.
AB  - There is increasing evidence that specific chromatin structures play an important
      role in the regulation of transcription in eukaryotes. The mouse mammary tumor
      virus (MMTV) promoter, which is reproducibly assembled into a phased array of six
      nucleosomes when introduced into cells, represents a particularly well-studied
      example. The second or B nucleosome of the phased array is disrupted in response
      to hormone stimulation, allowing the assembly of a preinitiation complex and the
      activation of transcription. In vitro experiments demonstrate that the assembly
      of the proximal promoter into chromatin is sufficient to prevent the binding of
      transcription factors such as nuclear factor 1. Consequently it is argued that
      chromatin serves to restrict the access of ubiquitous transcription factors in
      the absence of hormone stimulation. We have employed an in vivo exonuclease III
      (ExoIII)/Taq polymerase footprinting assay to study the hormone-dependent loading
      of transcription factors on the MMTV promoter. This assay makes use of stable
      mouse and human cell lines harboring bovine papilloma virus chimeras of the MMTV
      promoter attached to a reporter gene. To ascertain the significance of protein
      chromatin interactions vs protein-DNA interactions, we examined transcription
      factor binding to chromatin and nonchromatin templates of the MMTV promoter
      within the same cells. By the use of primers specific for each of the two
      distinct reporter genes, and restriction enzymes that generate entry sites for
      ExoIII, we can distinguish chromatin and nonnucleosomal templates in vivo. This
      system has allowed us to visualize the assembly of multicomponent transcription
      preinitiation complexes and to ascertain the consequences of defined chromatin
      structures on the binding of individual transcription factors in vivo.

PMID- 8993037
TI  - Analysis of in vivo nucleosome positions by determination of nucleosome-linker
      boundaries in crosslinked chromatin.
AB  - We describe a procedure for the determination of nucleosome boundaries that
      utilizes single-stranded mononucleosomal DNA obtained from fixed cells as the
      template in a primer extension assay. The procedure entails treatment of cells
      with formaldehyde, a reversible protein-DNA crosslinking agent used with the
      object of fixing the histone octamers to DNA in vivo, followed by preparation of
      nucleosomal DNA with micrococcal nuclease, reversal of the crosslinks, and
      isolation of the mononucleosomal material. Full-length single-stranded
      mononucleosomal DNA is then prepared and used as a template in a linear
      amplification primer extension assay. The use of single-stranded DNA templates
      eliminates interference from nicked DNA present in double-stranded preparations.
      Because of its reversibility, the use of formaldehyde permits the preparation of
      DNA suitable as a template in DNA synthesis. We present evidence demonstrating
      the efficiency of histone-DNA crosslinking and the reversibility of the
      crosslinking reaction as applied to the regeneration of native DNA, active in DNA
      synthesis. Use of this methodology removes the impact that mobility of the
      histone octamer and the presence of nicks on nucleosomal DNA have on the
      determination of nucleosome boundaries.

PMID- 8993039
TI  - Breast carcinoma: treat or overtreat.

PMID- 8993038
TI  - Ligation-mediated PCR for chromatin-structure analysis of interphase and
      metaphase chromatin.
AB  - Chromatin structure is becoming increasingly recognized as important for a full
      understanding of gene function and cell memory. With regard to cell memory, which
      involves the transfer of chromatin-encoded epigenetic information from one cell
      generation to another, the detailed structure of metaphase chromatin is of
      crucial importance. In this paper we describe methods for the use of dimethyl
      sulfate, DNase I, and potassium permanganate for in vivo footprinting and
      chromatin analysis, with special emphasis on studies of metaphase cells. We
      review the use of ligation-mediated PCR for the analysis of chromatin, including
      the human phosphoglycerate kinase promoter, and also report initial studies of a
      matrix attachment region near the human beta-interferon gene.

PMID- 8993040
TI  - Evaluation of ureteropelvic junction obstruction (UPJO) by diuretic renography.
AB  - Of 52 cases with 56 affected renal units having symptoms and signs suggestive of
      Ureteropelvic Junction Obstruction (UPJO) evaluated by conventional (F + 15)
      diuretic renography where frusemide is given 15 minutes post-injection of
      radiopharmaceutical m99TC.DTPA.F + 15, twelve (21%) showed a good clearance
      (group A), 16 (28%) showed partial (group B) and 28 (50%) a poor clearance
      pattern (group C) indicating a definite obstruction. A high flow (F-15) diuretic
      renography where frusemide is given 15 minutes prior to the radiopharmaceutical
      m99TC.DTPA, was done in 23 cases with 27 affected renal units. Eleven renal units
      showed a good clearance (group A). Of these, 7 (64%) showed a persistent good
      clearance, 3 (27%) converted to poor clearance and 1 (9%) to partial clearance
      pattern. Of 8 renal units in group B, 5 (63%) converted to poor clearance and two
      (25%) to good clearance on F-15 and one remained unchanged. All renal units which
      presented as poor clearance (group C) on conventional (F + 15) diuretic
      renography remained unchanged on high flow (F-15) diuretic renography. In
      majority of cases conventional (F + 15) renography gave a reliable assessment of
      the upper tract drainage, however, since equivocal group was resolved by the F-15
      and the intermittent obstruction group was definitely diagnosed, high flow (F-15)
      diuretic renography was more conclusive in assessment as compared to F + 15.

PMID- 8993041
TI  - Acute leukemias of childhood: a retrospective analysis of 62 cases.
AB  - Acute leukemia is reported to be less common in developing countries compared to
      non-Hodgkins lymphomas which is the most common childhood malignancy. A
      retrospective analysis was performed to identify the clinicopathological features
      of acute leukemias of childhood at the Oncology Department of Allama Iqbal
      Medical College, Lahore. The commonest malignancy in the under 15 years age group
      was leukemias (54%) followed by non-Hodgkins lymphomas (16%). Acute lymphocytic
      leukemia (ALL) was the commonest subtype (82%) followed by acute myeloid leukemia
      (16%). Peak incidence occurred in the 2.5-5 years age. The median duration of
      symptoms prior to diagnosis was 5 months. We conclude from our study that the
      incidence and clinicopathologic paediatric ALL is similar to that reported in the
      Western literature, unlike reports from other developing countries. Various
      environmental, viral and dietary carcinogens may play a major role in the
      etiology of leukemias.

PMID- 8993042
TI  - Needle localization of non-palpable breast lesions.
AB  - Screening mammography identifies suspicious, non palpable mammary lesions.
      Mammographic needle localization (MNL) is currently being used to facilitate
      excision biopsy of these lesions. Thirty-two patients underwent biopsies of the
      breast after MNL for non-palpable lesions. Mammographic indications for biopsy
      consisted of microcalcifications (48%), mass or abnormal density (21%) or
      mass+abnormal density (24%). The carcinoma was identified in four cases (12%).
      Two of these were in situ, one was microinvasive and one was frankly invasive.
      Three were treated with a modified radical mastectomy. One of these non palpable
      lesion demonstrated nodal metastasis but none showed distant metastasis. All
      radiologically detected abnormalities were removed and confirmed with repeat
      radiology. No complications were identified. MNL effectively localizes non
      palpable lesion of the breast and compliments accurate diagnosis and treatment of
      early carcinoma of the breast.

PMID- 8993043
TI  - Prevalence of seromarkers of HBV and HCV in health care personnel and apparently
      healthy blood donors.
AB  - Ninety-five health care workers and 91 controls were screened for seromarkers of
      both HBV (HBsAg, HBeAg, Anti-HBc) and HCV (anti-HCV) by ELISA. The control group
      showed a much higher frequency of seromarkers for both the viruses. HBsAg was
      positive in 5% of study group (health care personnel) and 14% of controls. Anti
      HBc as a marker of past HBV-exposure was positive in 28% of study group as
      compared to 36% of controls. Overall, 33% of study group and 48% of control
      showed one or the other marker of HBV Anti-HCV was positive in 4% of study group
      and 14% of controls. This study suggests that health care workers are not
      particularly a high risk group as compared to rest of the population.

PMID- 8993044
TI  - Stomal recurrence after total laryngectomy.
AB  - Radical laryngeal surgery was performed in 71 patients of stage III and IV
      laryngeal carcinoma. They were followed-up for the stomal recurrence. Stomal
      recurrence occurred in 5 (7%) patients, four of these had cervical nodal
      metastasis. The average time interval between laryngectomy and the stomal
      recurrence was 19 months. All the patients expired and the mean length of
      survival after the recurrence was 5.3 months.

PMID- 8993045
TI  - Subcutaneous phaeohyphomycosis: infection with pigmented fungi.

PMID- 8993046
TI  - 'Menouria'--a presentation of vesicouterine fistula.

PMID- 8993047
TI  - State of biostatistics in medical education and research in Pakistan.

PMID- 8993048
TI  - HEV exposure rate among clinically suspected cases of hepatitis infections.

PMID- 8993049
TI  - Scotland's enduring gift to medicine.

PMID- 8993050
TI  - The paradox of medicine: angry physicians and eager applicants.

PMID- 8993051
TI  - The questionable ferment of modern medicine.

PMID- 8993052
TI  - The prospects for tomorrow's doctors.

PMID- 8993054
TI  - Student remarks at the 1996 Affinity Group faculty recognition dinner:
      remodelling collaborative learning.

PMID- 8993053
TI  - The optimism of modern medicine.

PMID- 8993055
TI  - Promoting greater understanding: pairing medical students with families of
      children with disabilities.

PMID- 8993056
TI  - The Community Health Advocacy Program: changing the relations between communities
      and the medical campus.
AB  - Both CHAP and service-learning are unique new additions to medical education. The
      Medical School, Swearer Center for Public Service, and the Providence community
      have shown tremendous support and commitment. This commitment continues with the
      medical school's hiring of the Service-Learning Coordinator, who will help direct
      CHAP and organize service learning opportunities for medical students. CHAP
      provided me with an incredible learning experience, both frustrating and
      empowering. I was able to make sense out of medicine in the context of community
      health and also help others make sense of why an understanding of the communities
      in which they work and live was important to their medical education. On the
      whole I am pleased with the work and progress of CHAP as well as the service
      learning. I look forward to its future success and the newly forged partnerships
      of participating communities and the Brown Medical School campus.

PMID- 8993057
TI  - Preventing and responding to sexual harassment and sexual assault [a resource
      guide for medical students].

PMID- 8993058
TI  - Medice, cure te ipsum: lessons from Galen.

PMID- 8993059
TI  - Point of view: a house divided against itself: on Hippocrates and swimming with
      the sharks.

PMID- 8993060
TI  - Physicians-in-training in Rhode Island in 1996.

PMID- 8993061
TI  - Proposed oral cancer screening recommendations. Rhode Island Department of
      Health.

PMID- 8993063
TI  - Febrile seizures.

PMID- 8993062
TI  - Antiseptic myramistin possesses the strong anti-HIV properties.
AB  - The anti-HIV properties of cation detergent myramistin were studied. The dose
      dependent slowing down both of the HIV antigens accumulation in supernatants and
      the virus-dependent cell death was shown at myramistin concentrations 30
      micrograms/ml and 50 micrograms/ml in the MT-4 cell line. Simultaneous addition
      of the trace amount of the detergents and HIV-1 to the cells of Jurkat-tat line
      did not stimulate the HIV p24 production for 4 days of the experiment.

PMID- 8993064
TI  - Guillain-Barre syndrome.
AB  - GBS is an acquired, monophasic illness of the peripheral nervous system that
      usually presents with a gait disturbance and clinical features of pain, weakness,
      and areflexia. The etiology of the disease is immune-mediated and directed
      against the peripheral nervous system myelin, axon, or both. A careful history,
      physical examination, and routine laboratory tests are necessary to make a
      clinical diagnosis and to exclude other disorders that cause acute weakness.
      Laboratory tests that support the diagnosis, such as an increased CSF protein and
      abnormal electrodiagnostic studies, may be normal early in the illness. The most
      serious complications during the acute phase of the disease are respiratory
      failure and autonomic disturbances. Plasma exchange or IVIG shortens the duration
      and severity of the disease significantly. The prognosis for children who have
      GBS generally is excellent for full and functional recovery, using modern
      intensive care for respiratory support and the management of other complications.

PMID- 8993067
TI  - Index of suspicion. Case 1. Temporomandibular joint dysfunction syndrome as a
      cause of ear pain.

PMID- 8993066
TI  - Consultation with the specialist. Eye examinations in infants and children.

PMID- 8993065
TI  - Menstrual disorders.

PMID- 8993068
TI  - Index of suspicion. Case 2. Severe developmental delay, polyuria, and nocturia
      strongly suggests Bartter syndrome.

PMID- 8993069
TI  - Index of suspicion. Case 3. Tricyclic antidepressant (TCA) overdose.

PMID- 8993070
TI  - Assuring relevancy in changing times.

PMID- 8993071
TI  - Regaining control. With knowledge comes responsibility.

PMID- 8993072
TI  - DUR program moving ahead in fourth year.

PMID- 8993073
TI  - Billing for CRNP services.

PMID- 8993074
TI  - Are doctors ignoring living wills?

PMID- 8993075
TI  - Issues in polypharmacotherapy: focus on major depression.
AB  - Combination therapy is often used to improve efficacy, speed response, or
      attenuate an adverse effect of the initial pharmacotherapy. This article examines
      key issues in the use of polypharmacotherapy in the treatment of major depressive
      disorders. The addition of lithium and to a lesser extent triiodothyronine T3
      have been shown to be effective augmentation strategies in treatment-resistant
      depression. There is also evidence suggesting that lithium augmentation of
      tricyclic or serotonergic antidepressants and the combination of a serotonergic
      and noradrenergic antidepressant may hasten response. Some newer combination
      strategies in treating major depressive disorders are discussed.

PMID- 8993076
TI  - Pharmacokinetic and pharmacodynamic drug interactions with polypharmacotherapy of
      treatment-resistant affective and obsessive-compulsive disorders.
AB  - The concomitant use of multiple therapeutic agents in the treatment of resistant
      affective and obsessive-compulsive disorders increases the likelihood of a
      patient experiencing a drug-drug interaction at either the pharmacokinetic or
      pharmacodynamic level. Recent developments in molecular biology and
      pharmacogenetics have allowed the identification of which psychotropic agents are
      substrates, inducers, or inhibitors of specific hepatic cytochrome P450 isozymes.
      This increases the predictability of which drug combinations may lead to kinetic
      interactions. However the individual variability in kinetic disposition and
      pharmacodynamic response still limits the predictability of a drug-drug
      interaction in an individual patient treated with polytherapy.

PMID- 8993077
TI  - Issues in the monopharmacotherapy and polypharmacotherapy of obsessive-compulsive
      disorder.
AB  - Polypharmacotherapy is again becoming common place in clinical practice.
      Obsessive-compulsive disorder (OCD) as a single primary diagnosis is responsive
      exclusively to the serotonin reuptake inhibitors (SRIs) and this fact forms the
      major evidence supporting a central role for 5-HT (serotonin) in the pathogenesis
      of the disorder. Presently, the highly potent serotonin reuptake inhibitors
      clomipramine, fluoxetine, fluvoxamine, and paroxetine are the only agents
      approved by the Food and Drug Administration (FDA) for OCD, but there is evidence
      that other SRIs, such as sertraline, are also effective. Because OCD is often
      treatment refractory and highly comorbid with other psychiatric disorders, the
      use of polypharmacotherapy can be justified. Other serotonergic medications such
      as lithium, buspirone, trazodone, or fenfluramine may be useful as adjuvant
      treatments in treatment-refractory OCD and adjuvant antipsychotics are useful in
      tic disorders, personality disorders, and psychotic disorders. The usefulness of
      polypharmacotherapy should be tempered by adverse effects including the serotonin
      syndrome, withdrawal phenomena, extrapyramidal side effects, and drug-drug
      interactions.

PMID- 8993078
TI  - Polypharmacy in bipolar I disorder.
AB  - There are currently three mood stabilizers available for the maintenance
      treatment of patients with bipolar I disorder: lithium, valproate, and
      carbamazepine. Unfortunately, monotherapy with each of these conventional agents
      often fails. To improve outcome, clinicians utilize polypharmacy. Although the
      efficacy of this practice is largely unknown, because of the lack of controlled
      studies, data from the United States and Europe indicate polypharmacy is the rule
      rather than the exception. The few controlled trials that have been conducted
      indicate that (1) the specific combination of lithium plus imipramine provides no
      advantage over lithium monotherapy (notwithstanding the inadequacy of lithium
      monotherapy); (2) the specific combination of lithium and the depot neuroleptic
      flupenthixol provides no advantage over lithium monotherapy; and (3) the
      combination of lithium plus carbamazepine may be as effective as lithium plus
      haloperidol for acute and continuation treatment. Most of the literature on
      polypharmacy consists of case reports, retrospective chart reviews, and open
      label prospective studies, and describes the use of numerous combinations of
      medications, including lithium plus valproate, lithium plus carbamazepine, and
      valproate plus carbamazepine. Preliminary findings suggest these combinations may
      be effective, and that clozapine and high-dose levothyroxine may each be useful
      as well when combined with other drugs. Further research is necessary to formally
      evaluate whether these drug combinations are more effective than monotherapy.
      Until such studies are completed, certain general principles regarding side
      effects, pharmacodynamics, and pharmacokinetics should be kept in mind when
      prescribing two or more medications concurrently.

PMID- 8993079
TI  - Overview of somatization: diagnosis, epidemiology, and management.
AB  - This article outlines critical issues in the psychiatric assessment of patients
      presenting with medically unexplained physical symptoms that form the core of the
      somatoform disorders in current nosologies. The prevalence of these disorders in
      communities and clinical settings emphasizes that a majority of these patients
      are primary care service users rather than mental health clients. A brief review
      of previous studies on the pharmacological management of these syndromes with
      antidepressants highlights unique features of these disorders that are relevant
      to the design of double-blind studies. The promising results emerging from some
      of these studies bring new excitement to the field that may help counter the
      prevailing therapeutic nihilism, thus attracting new investigators to this area.
      Finally, several caveats are provided on issues of research design and
      interpretation for the benefit of those entering this field of research.

PMID- 8993080
TI  - Pharmacologic treatment of body dysmorphic disorder.
AB  - Body dysmorphic disorder (BDD), a preoccupation with an imagined or slight defect
      in appearance, has been described for more than a century and reported around the
      world. However, investigation into the treatment of this distressing and
      impairing disorder is just beginning. Available data on the pharmacologic
      treatment of BDD suggest that it often responds to serotonin reuptake inhibitors
      (SRIs), which may be preferentially effective for this disorder. Augmentation of
      SRIs with buspirone and neuroleptics, as well as combinations of SRIs, also
      appear promising. Available data also suggest that serotonin reuptake inhibitors
      may be effective for delusional BDD (a type of delusional disorder, somatic
      type). Because controlled treatment studies are lacking, however, these findings
      are preliminary. Controlled pharmacotherapy studies, which are under way, are
      greatly needed.

PMID- 8993081
TI  - The pharmacotherapy of hypochondriasis.
AB  - This article addresses the diagnosis and pharmacologic treatment of
      hypochondriasis. Diagnostic issues are reviewed briefly, focusing on the need for
      a thorough medical re-consideration of the patient's presenting symptoms. Because
      the diagnosis rests on the absence of a medical cause to account for the presence
      or intensity of the physical symptoms, neither self-report forms nor non
      medically trained interviewers should be used to definitively make the diagnosis
      of hypochondriasis. We review the case reports and small uncontrolled series on
      the pharmacologic treatment of hypochondriasis, emphasizing the growing body of
      evidence suggesting particular efficacy for the serotonin reuptake inhibitors.
      Preliminary results from an ongoing placebo-controlled trial of hypochondriasis
      using fluoxetine are presented. While the controlled trial supports the open
      treatment data in revealing a high rate of improvement among patients completing
      treatment with fluoxetine, it also demonstrates that many patients respond to
      placebo as well. In conclusion, although the traditional nihilistic attitude
      regarding the possibility of successful treatment of hypochondriacs appears no
      longer warranted, the question remains open as to whether SSRIs have particular
      efficacy in patients with hypochondriasis or whether nonspecific treatment
      effects are the primary cause of improvement.

PMID- 8993082
TI  - New psychosocial treatments for the outpatient management of bipolar disorder.
AB  - The psychosocial treatment of bipolar disorder has the potential to augment the
      efficacy of outpatient pharmacotherapy if it succeeds in enhancing the protective
      effects of the social and familial environment and the patient's adherence to
      drug regimes. We describe two manual-based psychotherapies under evaluation in
      controlled clinical trials: a family-focused psychoeducational treatment and an
      individual, interpersonally-oriented psychotherapy. Both target recently ill
      patients and are delivered in combination with standard pharmacotherapies on an
      outpatient basis. Results from the ongoing clinical trials suggest high patient
      retention rates for both models over the first year of treatment. Future research
      should focus on the appropriate sequencing of pharmacologic and psychosocial
      treatments, and the conditions under which psychosocial treatment will be most
      effective.

PMID- 8993083
TI  - Comparison of therapeutic modalities for mania.
AB  - The results of sequential therapeutic trials in hospitalized manic patients
      conducted over a 16-year period are summarized, followed by an analysis of pooled
      data to assess relative efficacy. No clinically important baseline differences
      were found in the patients admitted to these studies despite the long time span.
      They were not overly "difficult to treat" or treatment resistant, and most were
      discharged to the community. Nearly all outcome measures showed statistically
      significant differences between groups after 8 weeks of treatment. The best
      responses occurred in the patients who received a mean series of nine
      electroconvulsive therapy (ECT) treatments with sparing use of neuroleptics
      followed by lithium maintenance. The next best outcome was observed with lithium
      combined with low doses of standard neuroleptics or risperidone. The combination
      of carbamazepine and lithium had significantly fewer neurological side effects
      than moderate doses of haloperidol with lithium, with equivalent therapeutic
      results. Monotherapy with either lithium or carbamazepine was less effective than
      the combination treatments. Minor differences in study design may contribute to
      the variance in outcome.

PMID- 8993084
TI  - Venlafaxine or bupropion responders but not nonresponders show baseline
      prefrontal and paralimbic hypometabolism compared with controls.
AB  - In this study, 11 unipolar depressed outpatients received baseline (medication
      free) fluorine-18 deoxyglucose positron emission tomography scans prior to
      randomization to double-blind venlafaxine or bupropion monotherapy, with the
      option of a subsequent medication crossover. Based on Clinical Global impressions
      ratings, 6 of 11 responded to at least one medication. Regional cerebral glucose
      metabolic rate (rCMRglu) for these 6 responders was compared with 18 age- and
      gender-matched healthy controls; the 5 nonresponders were compared with 15
      matched healthy controls. Compared with healthy controls, responders showed
      decreased (normalized > absolute) left middle frontal gyral, bilateral medial
      prefrontal, and bilateral temporal rCMRglu. In contrast, nonresponders showed
      decreased (normalized > absolute) cerebellar rCMRglu. These preliminary data
      suggest that among never-hospitalized unipolar depressed out-patients, those
      showing baseline prefrontal and paralimbic hypometabolism may be more likely to
      show a positive response to standard antidepressant treatments such as
      venlafaxine or bupropion.

PMID- 8993085
TI  - A double-blind, placebo-controlled evaluation of the effects of orally
      administered venlafaxine on sleep in inpatients with major depression.
AB  - Venlafaxine, a member of a novel chemical class, phenethylamines, is a new
      antidepressant that inhibits neuronal uptake of serotonin, norepinephrine, and
      dopamine (in decreasing order of potency) at doses of 75 to 375 mg per day.
      Depression and antidepressant drugs are known to modify human sleep patterns. Our
      objective in this double-blind, placebo-controlled study was to assess the
      effects of venlafaxine on polysomnographic variables by comparing the effects of
      venlafaxine and placebo on sleep (hypnographic and all-night
      electroencephalographic [EEG] spectral analysis) and clinical measures (Hamilton
      Rating Scale for Depression [HAM-D], Montgomery-Asberg Depression Rating Scale
      [MADRS], and Clinical Global Impressions [CGI]) in inpatients with major
      depression (DSM-III-R). Following a 7- to 13-day placebo washout period, patients
      were randomly assigned to receive either placebo or venlafaxine (maximum dose 225
      mg/day) for up to 29 days. Sleep evaluations took place at baseline (3 nights
      immediately before entering the double-blind phase), after 1 week of treatment,
      and after 1 month of treatment. Sleep stage parameters and all-night spectral
      parameters were first tested by analysis of variance for repeated measures and
      then, if indicated, by two-tailed Student t-test. The results on psychiatric
      rating scales showed improvement from baseline in both treatment groups at all
      time points, with improvement tending to be greater in the venlafaxine group.
      Venlafaxine induced a decrease of sleep continuity (decreased total sleep time
      and increased wake time), an important increase in the onset latency of rapid eye
      movement (REM) sleep, and a decrease in total REM sleep duration. All-night sleep
      EEG frequency structure was not modified significantly by venlafaxine treatment
      as compared with placebo. In conclusion, venlafaxine, despite its novel chemical
      structure, shows a sleep profile comparable with that of most classical
      antidepressants.

PMID- 8993086
TI  - Valproate as an antidepressant in major depressive disorder.
AB  - Thirty-three outpatients who met DSM-IV criteria for major depressive disorder
      (MDD) with no history of manic or hypomanic symptomatology were enrolled in an 8
      week open trial of valproate. By Week 4, 15 of the 28 completers (54%)
      demonstrated a significant clinical response as defined by a score reduction of
      50 percent or more or a total score of 9 or lower on the Hamilton Rating Scale
      for Depression (HRSD). Mean HRSD scores of the completers decreased 48.8 percent
      at Week 4 (p < .0001). At Week 8, 19 of the 22 completers (86%) showed a
      significant response. Mean HRSD scores decreased from 22 +/- 5 at baseline to 7
      +/- 4 at Week 8 (p < .0001). With the intent-to-treat analysis at Week 8, 66
      percent were responders, and total group mean HRSD scores decreased 55 percent (p
      < .0001). The data suggest that valproate may be an effective treatment for MDD.
      Double-blind, placebo-controlled trials are needed to further document its
      efficacy in the treatment of MDD.

PMID- 8993087
TI  - Paroxetine is a novel nitric oxide synthase inhibitor.
AB  - The selective serotonin reuptake inhibitor, paroxetine, has been reported to
      inhibit cytochrome P450 activity. Nitric oxide synthase (NOS) is structurally
      homologous to cytochrome P450. Accordingly, in our study, we observed the effects
      of paroxetine on NOS activity. Seventeen ischemic heart disease (IHD) patients
      received paroxetine and fourteen received nortriptyline for treatment of clinical
      depression defined by a score of 17 or higher on the Hamilton Rating Scale for
      Depression (HAM-D). Serum nitrite and nitrate levels were significantly decreased
      following paroxetine treatment but not nortriptyline treatment. Paroxetine was
      also a more potent inhibitor of NOS enzyme activity than nortriptyline, as
      measured by the conversion of [14C] arginine to [14C] citrulline by hamster brain
      cytosols. In addition, paroxetine reversed the force-frequency relationship in
      isolated hamster papillary muscles in a manner analogous to that of known NOS
      inhibitors. Thus, paroxetine appears to be a novel NOS inhibitor in vitro and in
      vivo.

PMID- 8993088
TI  - A double-blind comparison of gepirone extended release, imipramine, and placebo
      in the treatment of outpatient major depression.
AB  - We report the results from one site of a two-site, double-blind, placebo
      controlled comparison study of gepirone extended release (ER) and imipramine in
      the management of major depression. In the study, 123 subjects with DSM-III-R
      major depression were randomized to 8 weeks of treatment with gepirone ER (10-60
      mg/day), imipramine (50-300 mg/day), or placebo. According to last observation
      carried forward (LOCF) analyses of 120 intent-to-treat subjects, both gepirone ER
      and imipramine were superior to placebo at Weeks 6 and 8 on the Hamilton Rating
      Scale for Depression 17- and 28-item (HAM-D-17 and HAM-D-28) instruments, the
      Clinical Global Impressions (CGI) Severity of illness scale, and the total Bech
      Six-Item Core Depression Cluster score. Gepirone ER was better tolerated than
      imipramine when judged by dropout rates for adverse events.

PMID- 8993089
TI  - Venlafaxine for panic disorder: results from a double-blind, placebo-controlled
      study.
AB  - Venlafaxine has demonstrated efficacy for depression, and recent reports and
      clinical experience suggest that it may be effective for the treatment of anxiety
      disorders as well. We present what we believe are the first data from a
      controlled study designed to test the efficacy of venlafaxine for the treatment
      of panic disorder. There were 25 patients enrolled at one site of a five-center
      study; 13 received venlafaxine and 12 received placebo. There were more dropouts
      for placebo than for venlafaxine (8/12 vs. 2/13) in this 8-week acute trial.
      Patients treated with venlafaxine experienced significantly greater global
      improvement than those on placebo and exhibited trends toward greater improvement
      on anxiety and depression symptoms as assessed by the Hamilton rating scales.
      These data encourage further evaluation of venlafaxine for the treatment of panic
      disorder.

PMID- 8993090
TI  - An open trial of nefazodone in adult patients with generalized anxiety disorder.
AB  - Generalized anxiety disorder (GAD) is a chronic disorder for which a variety of
      medications have been prescribed. Nefazodone is a recently released
      antidepressant that potently antagonizes the serotonin type 2A receptor and
      blocks uptake of norepinephrine and serotonin. It also antagonizes the serotonin
      type 2C receptor. Studies suggest this action may be anxiolytic. Twenty-one
      patients meeting DSM-IV criteria for GAD enrolled in an open 8-week trial of
      nefazodone were monitored by the Hamilton Rating Scale for Anxiety and the
      Clinical Global impressions scale. Fifteen of the 21 subjects completed the
      trial; 12 (80%) were rated as either very much or much improved, 1 (7%) as
      minimally improved, and 2 (13%) as unchanged. None was rated as worse. Nefazodone
      may be useful and well tolerated in the treatment of GAD. Theoretical questions
      about the neurobiological basis of GAD are also raised.

PMID- 8993091
TI  - Therapeutic effect and safety of adjunctive risperidone in refractory obsessive
      compulsive disorder (OCD).
AB  - It has been well established that more than 40 percent of patients with obsessive
      compulsive disorder (OCD) do not improve after an adequate trial with serotonin
      uptake inhibitors (SUIs). The first purpose of this trial was to compare the
      short-term efficacy and safety of two different strategies in a sample of
      treatment-refractory OCD patients: dose increase of the ongoing treatment versus
      the addition of another SUI. The second purpose was to investigate the short-term
      efficacy and safety of adjunctive risperidone in SUI-refractory OCD patients.
      Thirty-three OCD patients who were unimproved after a short-term treatment with
      clomipramine (150 mg/day) were admitted to the study. In the first part of the
      study, the dose increase of clomipramine was compared with sertraline addition,
      in an open-label manner. The addition of sertraline to the ongoing treatment
      appeared to be more effective and tolerable than the clomipramine dose increase.
      Seven (50%) of the 14 patients who were considered nonresponders after the first
      part of the study, showed good clinical improvement and good tolerability after
      risperidone augmentation. These results suggest that risperidone addition to
      ongoing SUIs may be useful in augmenting pharmacologic response in OCD.

PMID- 8993093
TI  - Longitudinal analysis of abnormal involuntary movements in long-term clozapine
      treated patients.
AB  - As part of a prospective efficacy and safety monitoring system, patients
      receiving clozapine are assessed monthly for dyskinetic events (DE), using the
      Abnormal involuntary Movement Scale (AIMS). Longitudinal analysis of 45 patients
      revealed 20 with baseline DE, 7 who developed emergent DE after a negative
      baseline assessment, and 18 patients with no DE symptoms throughout treatment
      with clozapine. Eight of the 20 patients with baseline DE were assessed to
      resolution of symptoms, with an average time of 261 +/- 188 days; 5 were
      evaluated until complete resolution of symptoms (AIMS = 0), with an average time
      of 691 +/- 462 days. The average time to onset of DE in emergent DE patients was
      238 +/- 179 days, and the average time to resolution was 347 +/- 179 days after
      diagnosis. Four patients attained complete resolution with an average time of 629
      +/- 293 days after diagnosis. It appears this emergent type of dyskinesia is
      different from other currently described dyskinesias. Overall, of the 27 patients
      having DE at any point in treatment, 15 of 27 (56%) had resolution of symptoms
      and 10 of 27 (37%) had complete resolution of DE. Clinicians should be aware of
      the utility of clozapine in dyskinesia and the extended time frame of response.

PMID- 8993092
TI  - Clozapine's effectiveness for patients in state hospitals: results from a
      randomized trial.
AB  - In our study, we examined the effectiveness of clozapine and compared it to the
      array of medication alternatives typically used in the public sector. Long-term
      patients in Connecticut's state hospitals who met Food and Drug Administration
      criteria for clozapine use were invited to participate in this randomized open
      label study. Participants (N = 227) were followed for 2 years. Compared with
      usual care, clozapine was associated with significantly greater reductions in
      side effects, disruptiveness, and hospitalization, but was not more effective in
      reducing symptoms or improving quality of life. The groups did not differ in
      likelihood of being discharged; however, once discharged, clozapine patients were
      less likely to be readmitted. The results of our study suggest that, compared
      with the flexible range of medication alternatives available, clozapine is an
      effective agent. However, at least with this patient population, clozapine did
      not produce the dramatic improvements is symptomatology or hospital utilization
      reported in clinical efficacy trials or suggested by mirror-image studies.

PMID- 8993094
TI  - Development and implementation of drug use evaluation (DUE) criteria for
      risperidone in an outpatient psychiatric setting.
AB  - Risperidone is a recently approved atypical antipsychotic that offers the
      advantages over existing typical antipsychotics of improved efficacy against
      negative symptoms and a decreased incidence of extrapyramidal side effects.
      However, risperidone is much more expensive than other antipsychotics. A drug use
      evaluation (DUE) was undertaken to assess the prescribing practices of
      risperidone in a large public adult psychiatric outpatient clinic. After a
      through literature review, criteria describing the appropriate prescribing of
      risperidone were approved after consultation with the medical staff. Criteria
      were developed to delineate appropriate patient selection, laboratory and
      clinical monitoring parameters, documentation, and outcome measures. After a
      chart review was conducted to evaluate existing prescribing practices, the
      criteria and results were presented to the medical staff and the appropriateness
      of the criteria were discussed. After 1 month, a second chart review was
      conducted to evaluate changes in prescribing practices in response to these
      criteria. Risperidone was prescribed to 44 patients in the outpatient clinic.
      Sixteen of these patients were resistant to treatment with traditional
      antipsychotics, 19 had developed intolerable extrapyramidal side effects during
      treatment with traditional antipsychotics, 10 had developed tardive dyskinesia,
      and 11 were noncompliant with other treatment regimens (some patients fell into
      more than one category). In 35 patients able to be evaluated for side effects,
      the most common were termed "activating side effects" and included restlessness,
      anxiety, insomnia, and unspecified activation. These side effects occurred in 9
      patients. Another 5 patients developed extrapyramidal side effects and 3 patients
      developed a tremor. The initial chart review showed deficiencies in several
      areas, including laboratory and clinical monitoring and documentation. After
      presentation of these results to the staff, a second review was conducted; the
      results demonstrated improvements in many of the areas that were originally
      deficient. In conclusion, it was shown that the criteria developed had an overall
      positive impact on the appropriate prescribing of risperidone.

PMID- 8993095
TI  - Clinical and economic aspects of risperidone treatment in adults with mental
      retardation and behavioral disturbance.
AB  - Risperidone, in conjunction with behavioral interventions, was used to reduce
      aggression and assault, self-injury, and property destruction in 33
      institutionalized adults with mental retardation. Target behavior frequencies,
      global assessments by staff, wages earned by patients, and the institution's
      costs for assault-related injury to staff and lost work time were evaluated
      before and after initiation of risperidone treatment. Risperidone (1-8 mg/day)
      was associated with a 50 percent or greater reduction in at least one target
      behavior frequency in 61 percent of patients. After 6 months of treatment, 85
      percent of patients were rated "improved" and 15 percent were rated "unchanged."
      Treated patients' wage earnings increased by 37 percent. The number of staff work
      days lost because of assault by treated patients decreased from 444 during the 6
      months before initiation of risperidone to 29 during the 6 months after
      initiation. Sedation, pseudoparkinsonism, possible akathisia, and weight gain
      were noted in 9-12 percent of patients. No patients were withdrawn from
      risperidone because of intolerable side effects or lack of efficacy. The results
      of this evaluation suggest that risperidone is effective and well tolerated in
      this population.

PMID- 8993096
TI  - Glycinergic augmentation of NMDA receptor-mediated neurotransmission in the
      treatment of schizophrenia.
AB  - Phencyclidine (PCP) induces a psychotic state closely resembling schizophrenia in
      normal individuals. PCP and related agents induce their unique behavioral effects
      by blocking neurotransmission mediated at N-methyl-D-aspartate (NMDA)-type
      glutamate receptors, indicating that dysfunction of NMDA receptor-mediated
      neurotransmission may play a crucial role in the pathophysiology of
      schizophrenia. NMDA receptors are activated by the amino acids glutamate and
      glycine, working at independent binding sites. Glutamate cannot be administered
      exogenously because of excitotoxicity. In contrast, glycine administered
      exogenously may potentiate NMDA receptor-mediated neurotransmission in vivo
      following peripheral administration. In rodents, glycine is effective in
      elevating brain glycine levels and reversing PCP-induced hyperactivity at doses
      of 0.8 g/kg and above. Three studies have now been completed utilizing moderate
      to high (0.4-0.8 g/kg/day) doses of glycine, added to neuroleptics, for the
      treatment of schizophrenia. Across studies, 15 to 30 percent improvement in
      negative symptoms was observed with no corresponding worsening of positive
      symptoms. Although preliminary, these studies indicate that dietary
      supplementation with glycine or treatment with other glycinergic agents may be
      effective in the treatment of schizophrenia.

PMID- 8993097
TI  - Magnetoencephalographic assessment of spontaneous brain activity in
      schizophrenia.
AB  - Magnetoencephalography (MEG) offers an attractive alternative to
      electroencephalography (EEG) in the assessment of psychiatric patients. In this
      study, a whole-head biomagnetometer equipped with 122 super-cooled sensors was
      used to assess spontaneous neuromagnetic activity in 11 unmedicated schizophrenic
      patients and 8 schizophrenic patients medicated for more than 8 weeks with novel
      antipsychotics (5 of whom were initially studied as part of the unmedicated
      group). Ten normal (nonpsychiatric) controls were also examined. For each
      subject, 5 minutes of data were collected in an eyes-closed state. Data were
      visually inspected for gross MEG abnormalities, and average power spectra were
      calculated for the data at each sensor. No gross abnormalities were identified
      for control subjects. One unmedicated schizophrenic patient showed epileptiform
      sharp waves, and 4 showed abnormal slow waves. No gross MEG abnormalities were
      found for the medicated schizophrenic group (which included 3 patients who had
      previously shown slow waves in the unmedicated state). Spectral analyses showed
      that the schizophrenia patients demonstrated lower alpha power and peak frequency
      than controls. The data are interpreted within the context of previously reported
      magnetic resonance abnormalities of the thalamus.

PMID- 8993098
TI  - Health state valuations from the general public using the visual analogue scale.
AB  - In the clinical and economic evaluation of health care, the value of benefit
      gained should be determined from a public perspective. The objective of this
      study was to establish relative valuations attached to different health states to
      form the basis for a 'social tariff' for use in quantifying patient benefit from
      health care. Three thousand three hundred and ninety-five interviews were
      conducted with a representative sample of the adult British population. Using the
      EuroQol health state classification and a visual analogue scale (VAS), each
      respondent valued 15 health states producing, in total, direct valuations for 45
      states. Two hundred and twenty-one re-interviews were conducted approximately 10
      weeks later. A near complete, and logically consistent, VAS data set was
      generated with good test-retest reliability (mean ICC = 0.78). Both social class
      and education had a significant effect, where higher median valuations were given
      by respondents in social classes III-V and by those with intermediate or no
      educational qualifications. These effects were particularly noticeable for more
      severe states. The use of such valuations in a social tariff raises important
      issues regarding the use of the VAS method itself to elicit valuations for
      hypothetical health states, the production of separate tariffs according to
      social class and/or education and the appropriate measure of central tendency.

PMID- 8993099
TI  - Quality of life in pre-adolescence: a 17-dimensional health-related measure
      (17D).
AB  - Although interest in the health-related quality of life (HRQOL) of children has
      increased in the last years, validated methods for assessing the HRQOL- and
      especially the perceived HRQOL-of children have been missing. We introduced a 17
      dimensional, illustrated, generic measure of perceived HRQOL (17D) for pre
      adolescents, and demonstrated its application to three populations of children
      aged 8-11 years: (1) 244 normal schoolchildren; (2) 22 patients surviving organ
      transplantation and (3) 10 patients with genetic skeletal dysplasias. The HRQOL
      scores and profiles of the patients differed significantly according to the
      diagnosis, giving support to its construct validity. The reliability of the
      measure was high: its repeatability coefficient was 95%. As a structured
      interview of 20-30 minutes, the measurement burden is reasonable. We conclude
      that the assessment of quality of life of pre-adolescents can and should be based
      on data collected from the children themselves. Our initial experience indicates
      that 17D is comprehensive, reliable, and valid.

PMID- 8993100
TI  - Construction and validation of a quality of life questionnaire in chronic lower
      limb venous insufficiency (CIVIQ).
AB  - Quality of life may be considerably reduced in patients who are suffering from
      chronic lower limb venous insufficiency, although existing generic quality of
      life instruments (NHP, SF-36 or SIP) cannot completely identify their specific
      complaints. The Chronic Venous Insufficiency Questionnaire (CIVIQ) has been
      developed by iterative process. First, a pilot group of 20 patients was used to
      identify a number of important features of quality of life affected by venous
      insufficiency, other than physical symptoms of discomfort. A second study
      involving 2,001 subjects was used to reduce the number of items. Subjects were
      asked to score both the severity of their problems and the importance they
      attributed to each problem on a 5-point Likert scale. The importance items found
      in patients with venous insufficiency were subjected to factorial analyses (PCA,
      PAF). The final version is a 20-item self-administered questionnaire which
      explores four dimensions: psychological, physical and social functioning and
      pain. Internal consistency of the questionnaire was validated for each dimension
      (Cronbach's alpha > 0.820 for three out of four factors). Reproducibility was
      confirmed in a 60 patient test-retest study. Pearson's correlation coefficients
      for both the four dimension subscales and for the global score at 2-week
      intervals were greater than 0.940. Finally, the questionnaire was tested in a
      randomized clinical trial of 934 patients in order to assess responsiveness and
      the convergent validity of the instrument, together with the patient's own
      quality of life. This study demonstrated that convergence was valid: Pearson's
      correlation coefficients between clinical score differences and quality of life
      score differences were small (from 0.199-0.564) but were statistically different
      from 0 (p < 0.001). Standardized response mean (SRM) and effect size (ES) were
      calculated to assess sensitivity to change. SRM and ES both demonstrated
      considerable responsiveness to change (> 0.80). Reliability, face, content,
      construct validity and responsiveness were also determined for this specific
      quality of life questionnaire relating to venous insufficiency. Results suggest
      that this questionnaire may be used with confidence to assess quality of life in
      clinical trials on chronic venous insufficiency.

PMID- 8993102
TI  - The Internet: a modern Pandora's box?
AB  - Two different views of the Internet are presented. One is from the perspective of
      an author who has written a personal account of her own breast cancer experience,
      while the other is from the perspective of a cancer researcher who is interested
      in quality of life research. The article is written in a format that reflects the
      somewhat informal style of messages sent to Internet discussion groups. For
      better or worse, the Internet has arrived as a force in our lives, and medical
      information and support constitute two of its more important uses. Both authors
      agree that the novel medium of the Internet provides a unique opportunity to
      create a true partnership of health care providers and consumers.

PMID- 8993101
TI  - The interpretation of scores from the EORTC quality of life questionnaire QLQ
      C30.
AB  - While quality of life (QOL) assessment is becoming more common, interpreting the
      results remains problematic. This paper demonstrates an approach to developing
      clinically-based interpretations for QOL outcomes, using the QLQ-C30 as an
      example. The results from 14 published QLQ-C30 studies which group patients by
      performance status, weight loss, toxicity, extent or severity of disease are
      collated. Groups with lower clinical status generally have worse QOL. The largest
      differences are between performance status groups, and the smallest differences
      are between groups of patients with local disease and those with metastases. The
      physical and role scores have the largest ranges of means across patient groups,
      and show the largest differences between clinical groups, while the cognitive and
      emotional scores have the smallest ranges of means and differences. Sicker groups
      have larger score standard deviations than healthier groups. Relatively large and
      small means and differences, and corresponding effect sizes, are presented.
      Collectively, the results provide a sense of the relative sizes of means and of
      differences, and of the types of clinical groups which give rise to them, thereby
      providing clinically-based benchmarks by which to interpret QLQ-C30 results.

PMID- 8993103
TI  - Animal models.

PMID- 8993104
TI  - Kinetics of Trypanosoma cruzi destruction in the mouse spleen.
AB  - Massive destruction of parasitized splenic macrophages was histologically
      observed at the height of a virulent infection caused by Trypanosoma cruzi (Y
      strain) in the mouse. This was coincident with a sudden drop in parasitemic
      curve. Most of the animals died at this point, probably due to the liberation of
      toxic products, such as TNF, following the massive destruction of parasitized
      cells. However, parasitized-cell destruction indicated the transition from
      susceptibility to resistance. Although it has been extensively studied in vitro,
      this study contributes with the morphological counterpart observed in vivo by
      optical and electron microscopy. When infected animals were specifically treated
      during early infection transition to chronic phase was immediately observed
      without splenic parasitism. Animals that apparently recovered from massive cell
      destruction in the spleen showed evidences of a rapid restoration of splenic
      architecture.

PMID- 8993105
TI  - Human parvovirus B19 infections among exanthematic diseases notified as measles.
AB  - A total of 1397 sera collected from 1095 cases of exanthematic disease notified
      as measles in ES and RJ states during July 1992 to December 1994 were
      investigated. These sera were first tested for measles and rubella specific IgM.
      When they proved negative, they were tested for B19 specific IgM by an enzyme
      immunoassay. B19 infection was confirmed in 27 (2.5%) of these cases. Sera from
      194 negative cases for measles and rubella IgM received from other Brazilian
      states were also investigated and B19 infection was confirmed for 11 of them.
      Sera from these 38 IgM positive cases for B19, were tested for anti-B19 IgG by an
      enzyme immunoassay and for B19 DNA by dot blot hybridization. Anti-B19 IgG
      antibodies were detected in most of the acute sera. B19 DNA was detected in the
      acute serum of one patient that had been splenectomized before. As the exanthem
      caused by human parvovirus infection may be clinically diagnosed as rubella, it
      could be important to diagnose B19 infection in Brazil since it is becoming
      prevalent as the cause of rash in countries where rubella is controlled by
      vaccination.

PMID- 8993106
TI  - Biodemes and zymodemes of Trypanosoma cruzi strains: correlations with clinical
      data and experimental pathology.
AB  - With the objective of establishing biological and biochemical characteristics of
      a significant number of Trypanosoma cruzi strains from different geographical
      areas, 138 strains isolated from naturally infected humans, triatomine or
      vertebrate hosts were studied; 120 were isolated from different areas of Brazil
      and 18 from other South and Central American countries. Inocula from triatomine
      or culture forms were injected into suckling Swiss mice, followed by passages
      into mice 10 to 12 g. Biological characters and histopathological study permitted
      the inclusion of the strains into three Types or biodemes: I, II, III. Isoenzymic
      analysis confirmed a correspondence between the biodemes and zymodemes: Type I
      and Z2b, Type II and Z2, Type III and Z1. Results showed the ubiquitary
      distribution of the several types of strains. The predominance of the same Type
      and zymodeme in one geographical area was confirmed: Type II strains among the
      human cases from eastern Bahia and east of Goias; Type III strains from humans of
      north Brazil and Central America and from silvatic vectors or vertebrates from
      other geographical areas. The biological types of strains correlate with
      different histopathological lesions considering cardiac involvement and neuronal
      lesions. These findings suggest that the biological behavior together with
      isoenzymes patterns and pathological pictures in the vertebrate host can be an
      important tool for establishing correlations between strains behavior and clinico
      pathological manifestations of Chagas' disease in different geographical areas.

PMID- 8993107
TI  - A short review of the previous and current epidemiological situation of
      schistosomiasis in China.
AB  - Schistosomiasis japonica has long been endemic in the People's Republic of China.
      In the 1950s, the number of the infected persons was estimated at 10 million;
      infected snail habitats were estimated at more than 14 billion square metres and
      infected cattle at 1.2 million. After schistosomiasis control measures were
      carried out, it was a great success. According to the survey of 1989, infected
      persons were estimated at 0.95 million; infected snails at 3.47 billion and
      infected cattle at about 0.1 million. These results compared with those of the
      1950s show big reductions in prevalence rates 90.5%, 75.2% and 91.6%,
      respectively. At present, the disease is a threat in the marshland and lake
      regions and the high mountainous regions. To maintain the success achieved in
      effective control and to bring the yet endemic marshland and lake regions and
      mountainous areas under control are hard and long-term tasks confronting the
      People's Republic of China.

PMID- 8993108
TI  - Human immune response to triatomine embryo extract.
AB  - Dipetalogaster maximus embryo extracts were used to stimulate peripheral blood
      mononuclear cells (PBMC) and in ELISA with sera either from Trypanosoma cruzi
      infected or non-infected individuals. The results showed that there was
      significant proliferative response and high antibody, titers in sera of chagasic
      patients.

PMID- 8993109
TI  - Treatment of hypercholesterolemia in patients undergoing multiple coronary
      angioplasties.
AB  - BACKGROUND: Hypercholesterolemia is a known risk factor for coronary artery
      disease (CAD). Multiple studies have shown that its treatment will reduce the
      rate of progression of coronary atherosclerosis and lead to regression of the
      atherosclerotic process. Recent studies have also shown impact on mortality.
      Angioplasty (PTCA) is a well established revascularization procedure for many of
      these patients. In this study we investigated whether or not therapy for
      hypercholesterolemia in patients undergoing elective PTCA had been instituted
      and, if so, whether desirable cholesterol levels had been achieved. METHODS: We
      reviewed the charts of 129 patients (pts) who were consecutively admitted for
      elective PTCA between September 1993 and August 1994. All pts. had at least one
      PTCA in the past and all of them had the diagnosis of hypercholesterolemia. The
      list was made using a computer search of all pts. meeting the previous two
      diagnoses. Pts on whom PTCA was performed in the setting of acute ischemic events
      were excluded as well as pts with no known history of hypercholesterolemia.
      RESULTS: In 13 out of 129 pts., it was not possible to find cholesterol levels.
      The 116 pts in whom cholesterol levels were available were divided in two groups.
      Group I (54 pts.-46.5%) included pts. not being treated with any lipid lowering
      agent and group II (62 pts.-53.5%) included pts being treated with at least one
      of those drugs. Both groups were further subdivided into "A" and "B", depending
      on whether the PTCA was being performed because of a "new" lesion or because of
      "restenosis", respectively. Group IA had a total of 31 pts, IB 23 pts, IIA 29 pts
      and IIB, 33 pts. Group I pts had an average of 3.40 PTCA's and a mean cholesterol
      level of 227 mg/dl. Group II pts had an average number of PTCA's of 3.34 and a
      mean cholesterol level of 228 mg/dl. Group IA had an average number of PTCA's of
      3.65 and a mean cholesterol level of 221 mg/dl; for group IIA these values were,
      respectively, 3.17 and 221 mg/dl. Group IB had an average number of procedures of
      3.09 while for group IIB this number was 3.49; the mean cholesterol levels were,
      respectively, 235 mg/dl and 234 mg/dl. None of these differences is statistically
      significant. Group I had 14 pts (26%) with cholesterol levels below 200 mg/dl
      while group II had 16 pts. with cholesterol levels below 200 mg/dl (26%). In
      group I, 8 pts (14%) had lipid profiles documented. Only 1 pt. had an LDL level
      below 100 mg/dl and only 3 pts had an LDL level below 130 mg mg/dl. In group II,
      15 pts (24%) had a lipid profile documented. Of these, no pt. had an LDL level
      below 100 mg/dl and only 4 pts had an LDL level below 130 mg/dl. CONCLUSIONS: A
      significant percentage of pts. undergoing multiple PTCA's are not being treated
      or monitored adequately for hypercholesterolemia despite aggressive invasive
      management.

PMID- 8993110
TI  - Quantitative structure-activity relations by the MTD-method for binding of
      nonapeptides to the HLA-A2.1 molecule.
AB  - Binding of large series of nonapeptides to the HLA-A2.1 molecule was studied by a
      group of Sette in order to predict strongly binding peptides with possible
      therapeutic interest. Here we establish QSAR-s for these series. The MTD-method
      was used for steric requirements concerning amino acidic side chains as well as
      side chain hydrophobicities. Binding of these peptides to the HLA-A2.1 molecule
      is favored by a lipophylic character of side chains for the anchor position 2 and
      9 and for positions 1,3 and 6 and by steric features that allow predictions for
      some modified amino acidic residues in these positions that should increase the
      peptide-HLA-molecule affinity.

PMID- 8993111
TI  - The influence of some vegetable extracts on the in vitro adherence of mouse and
      human lymphocytes to nylon fibers.
AB  - We found that the total watery extracts obtained from roots of various plants
      such as Symphytum officinale, Phytolacca americana etc, precipitate human
      glycoproteins, agglutinate sheep red blood cells (SRBC) and stimulate lymphocyte
      adherence to nylon fibers. Five out of seven extracts precipitated human
      gammaglobulins and one of seven obviously agglutinate SRBC. If these cells were
      pretreated with rabbit antibodies against SRBC, all extracts agglutinated the
      cells at various degrees of intensity, the most active being Phytolacca
      americana. The adherence of mouse but not human lymphocytes to nylon fibers was
      stimulated by extracts of Symphytum officinale and Phytolacca americana. This
      process was neither stimulated nor inhibited by Mannose (Man), Galactose (Gal),
      Glucose (Glc), N-acethyl Galactose (GalNAc) and N-acethyl Glucose (Glc-NAc).
      These biological effects of the plant extracts could be the expression of a
      lectin-like ability to bind various sugars other than those mentioned. The
      results suggest the possibility of using different extracts as means to point out
      the presence in serum or at the cellular level of some carbohydrates influencing
      the cellular adhesion, phenomenon which plays an important role in the functions
      of hematopoietic cells.

PMID- 8993112
TI  - Level of ventricular myosin light chains 1 and 2 determined by ELISA in serum of
      patients with acute myocardial infarction.
AB  - The serum level of human ventricular myosin light chains 1 and 2 was determined
      by competitive ELISA assay in 56 patients, of whom 26 with acute myocardial
      infarction (18 with simple AMI and 8 with complex AMI), 10 with unstable angina
      pectoris and 20 healthy subjects. The serum level of human ventricular myosin
      light chains 1 and 2 (HVMLC1 and HVMLC2) in healthy subjects was of 6-10 ng/ml.
      Sensitivity of the assay was 10 ng/ml, and the working range was 10-100 ng/ml. In
      all AMI patients the HVMLC1 serum level exceeded 2-3 times the reference range
      within the first 24 hours after the onset of chest pain, the mean (+/- ISD) peak
      concentration was of 45.7 (+/- 13.6) ng/ml (simple AMI) and 64.22 (+/- 18.5
      ng/ml) (severe AMI) 48 hours after infarction and it remained significantly
      higher than the normal value for another 7-10 days after the onset of infarction.
      The serum HVMLC2 concentration exceeded 10 ng/ml 48 hours after infarction, with
      a mean (+/- 1SD) peak concentration of 37.8 (+/- 10.4) ng/ml (simple AMI) and
      53.8 (+/- 16.1) ng/ml (complex AMI) 90 hours after the onset of infarction and
      remained at high values for another 4-7 days. In two of ten patients with
      unstable angina pectoris LC2 increases above 10 ng/ml. The prolonged release of
      HVMLC1 and HVMLC2 in serum for 4-7 days after the onset of myocardial infarction
      may facilitate the retroactive detection of infarction, hence the extension of
      myocardium necrosis.

PMID- 8993113
TI  - Flow cytometric study of the epirubicine accumulation modulation in the human
      erythrocytes by a Nocardia opaca fraction.
AB  - The effect of the "Nocardia lysozyme digest" (NLD) obtained from Nocardia opaca
      on the Epirubicine accumulation in erythrocytes was studied by flow cytometry. It
      was shown that the number of fluorescent cells increased under the NLD action due
      to the increased membrane permeability for epirubicine. An opposite effect was
      also recorded consisting in the decrease of the relative fluorescence intensity
      per cell. This effect was attributed to the fluorescence quenching by the oxygen
      metabolites produced by NDL. In this paper we present some results of the study
      of the NLD effect on the epirubicine (Epir) accumulation in the erythrocytes (E).
      It is shown by flow cytometry that the Epir accumulation in the red cells is
      modified by the presence of the NLD fraction.

PMID- 8993114
TI  - Neutralization epitope patterns of poliovirus strains isolated from cases of
      acute spinal paralysis and from healthy vaccinated children.
AB  - By using a battery of poliovirus neutralizing monoclonal antibodies received from
      the Pasteur Institute, Paris, we carried out the study of the patterns of
      neutralization epitopes of more than 300 poliovirus strains isolated from cases
      of acute spinal paralysis and from healthy vaccinated children. We tried to find
      out the utility of this test for establishing the origin (wild or Sabin) of a
      poliovirus strain and the possible evolution of the pattern of neutralization
      epitopes. The study of the neutralization epitopes was carried out by
      neutralization index assay (NI). The neutralization index represents the
      difference between the titers of poliovirus strain determined in parallel in the
      absence, as well as in the presence of constant concentration (predetermined) for
      each monoclonal antibody. An epitope was considered to be present for a NI > or =
      2 and absent for a NI < or = 1.5. For types 1 and 3 polioviruses, Sabin-like
      epitopes have never been found to be present simultaneously with wild type
      epitopes on the same virus particle. Therefore, examination of the epitope
      pattern of these strains is very useful for intratypic differentiation. On the
      other hand, in type 2 poliovirus strains, Sabin and wild type epitopes sometimes
      coexist, in various combinations, thus rendering the interpretation of the
      results rather difficult.

PMID- 8993115
TI  - Study of the incidence of intestinal and systemic parasitoses in a group of
      children with handicaps.
AB  - A high incidence of parasitic infections was shown by the study of children with
      physical and psychic handicaps. In 231 children examined we diagnosed 294
      parasitic infections as follows: 42 (18.1%) with Giardia intestinalis 6 (2.59%)
      with Entamoeba histolytica 36 (15.5%) with Hymenolepis nana 21 (9.9%) with
      Strongyloides stercoralis 16 (6.9%) with Ascaris lumbricoides 92 (39.86%) with
      Tricocephalus dispar 38 (16.4%) with Enterobius vermicularis 7(3.03%) with
      Cryptosporidium sp. Also, by immunodiagnosis 29 cases of Toxoplasmosis (12.5%)
      and 7 cases of Toxocarosis (3.03%) were pointed out. The clinical examination
      revealed that the main symptoms were troubles of appetite (both anorexia and
      hyperorexia)-67.9% intestinal transit disorders-48.4% cutaneous rash (4.7%). Two
      series of specific treatments diminished the incidence at 38% (after the first)
      and at 28.5% (after the second). By disappearance of the troubles due to the
      parasitic infections, the state of children with physical and psychic handicaps
      clinically improved; so, we may consider as a further necessity the screening of
      all those children for such diseases.

PMID- 8993116
TI  - The mosquitoes (Diptera:Culicidae) from Romania: an annotated checklist and
      bibliography.
AB  - A checklist of 55 species of Romanian mosquitoes is compiled from literature. A
      brief history of mosquito records from Romania and some explanatory notes about
      the checklist and bibliography are also provided.

PMID- 8993117
TI  - Antibiotics and bacterial resistance. A few elements of genetic basis for this
      relationship.
AB  - In the preantibiotic era, many people died of bacterial infections caused by such
      pathogens as Staphylococcus aureus and Streptococcus pyogenes, Streptococcus
      pneumoniae and Mycobacterium tuberculosis. Antibiotics have reduced the mortality
      from infectious diseases but not the prevalence of these diseases. It was not
      long after the clinical introduction of the first antibiotics in the 1950s that
      the first reports of bacterial resistance began to appear. Use, and often abuse
      or misuse, of antimicrobial agents has encouraged the evolution of bacteria
      toward resistance, resulting often in therapeutic failure. In the beginning, new
      antibiotics have always appeared in plenty of time to provide new cures for
      diseases caused by resistant bacterial pathogens. Also, some clinically important
      groups of bacteria showed no signs of major increases in resistance. For example,
      S. pneumoniae strains remained susceptible to penicillin long after other
      bacteria had become resistant to it. Recent developments of bacteria resistance
      to antibiotics are indeed disquieting.

PMID- 8993118
TI  - CD3+, CD16+, CD56+ cells: a novel subset of T lymphocytes from patients with
      Balkanic nephropathy.
AB  - Balkanic Nephropathy (BN) is characterized by: an incidence limited to a
      geographic area; a familial character and a slow progressive evolution towards
      chronic renal failure associated with the symmetrical reduction of the kidney
      size. The aim of our study was to find out the immune alterations in BN
      pathology. The analysis of various subpopulations of peripheral lymphocytes
      obtained from patients with BN showed no quantitative differences in comparison
      with healthy subjects and healthy subjects from the endemic area. In the BN
      patients we identified a novel subset of the CD3+, CD16+, CD56+ cells expressing
      the phenotypic characteristics of both T lymphocytes and NK cells.

PMID- 8993119
TI  - Cross-linking of CD38 molecules induced expression of interleukin-2 receptor (IL
      2R) and HLA-DR on human thymocytes.
AB  - CD38 is a 45 KD glycoprotein which is mainly expressed on early lymphoid
      progenitors and plasma cells. Role and function of CD38 on thymocytes and plasma
      cells has not yet been elucidated. By cross-linking of CD38 molecules using a
      specific monoclonal antibody on thymocytes and a neoplastic T cell line (Jurkat),
      it was shown that percentage of HLA-DR and IL-2R molecules is significantly
      upregulated. Moreover, CD11a and CD18 were among two adhesion molecules which
      showed a sharp increase in expression, whereas no changes on expression of CD11b,
      CD44 and CD54 were detected. Spontaneous proliferation of Jurkat cell line after
      addition of different concentrations of CD38 monoclonal antibody was unchanged.

PMID- 8993120
TI  - Growth parameters and rate of expression of some CD markers in sorted and not
      sorted macrophage cultures.
AB  - Several parameters of in vitro culturing were investigated for two kinds of human
      macrophages cell fractions, i.e. sorted by flow cytometry and not sorted, as
      follows:--growth ability during serial in vitro passages, and--percent rate of
      CD13, CD14 and CD33 expression at different in vitro passage levels. Results
      point out the ability of sorted cells to survive to a higher number of serial
      passages. A dramatical loss of CD13 and especially CD33 markers was noticed
      during culturing within the not sorted cells, as compared to homologous sorted
      ones.

PMID- 8993121
TI  - Clinical usefulness of rapid serodiagnosis in pulmonary tuberculosis by ELISA
      with glycolipidic antigens extracted from Mycobacterium tuberculosis and with
      whole BCG suspension.
AB  - Antibodies against Mycobacterium tuberculosis glycolipids and whole BCG
      suspension were determined by ELISA on 58 sera from hospitalized patients with
      presumptive pulmonary tuberculosis and on 127 sera from control subjects. The
      experimental results demonstrated that the glycolipids are more adequate to be
      used as antigens than whole BCG suspension, as high sensitivity of the test was
      obtained. By using only one antigen, ELISA becomes more efficient in rapid
      diagnosis. ELISA with glycolipidic antigens should be used as a supporting test
      for direct smear examination in the diagnosis of pulmonary tuberculosis,
      especially in cases when repeated bacterial methods failed to prove the presence
      of M. tuberculosis.

PMID- 8993122
TI  - Modulating the expression of some biological membrane glycoconjugates by a
      Nocardia opaca fraction.
AB  - By some hemagglutination (HA) studies it was proved that NLD (the lysozyme digest
      fraction of Nocardia opaca) interacts with the Sendai virus envelope glycoproteic
      receptors, but not with those of the Beijing 353/89 H3N2) Influenza virus. Very
      likely the inhibition is due to the presence of some GAL lectins in NLD: The
      erythrocytes agglutinability (by the Sendai virus and by the Beijing 353/89 H3N2)
      Influenza virus is enhanced by their incubation with galactose.

PMID- 8993123
TI  - Serological identification of Shigella flexneri strains by the coagglutination
      reaction.
AB  - Several variants of reagents were prepared by coupling type (I, II III, IV, V and
      VI) and group (3, 4, 6 and 7, 8, 9) anti-Shigella flexneri sera with protein A-
      containing staphylococcal suspension. For most serum lots coagglutination led to
      a 1/10 minimum dilution. However, different efficiencies were reported between
      serum lots and even within the same type or group. No improvement by the
      coagglutination reaction could be obtained for one lot from group 3, 4 and 7, 8,
      9 sera and for both type IV serum lots. The coagglutination reactions were
      specific both with collection strains and with recently isolated strains and the
      two staphylococcal suspension lots showed an identical behaviour. Coagglutination
      may be used for obtaining a better efficiency of type and group. Shigella
      flexneri sera but this varies in terms of the serum lot and the
      serum/Staphylococcus combination used.

PMID- 8993124
TI  - Research on congenital toxoplasmosis.

PMID- 8993126
TI  - Asthma practice guidelines: common sense, expert opinion or evidence based
      approach?

PMID- 8993125
TI  - Antivenom activity of opossum (Didelphys marsupialis) serum fractions against
      Uracoan rattlesnake (Crotalus vegrandis Klauber, 1941) venom.
AB  - In this work, we have found strong evidence for the presence of an opossum serum
      which is highly proficient in inactivating the neurotoxic fractions of Uracoan
      rattlesnake (Crotalus vegrandis) venom. Analyses of strained electrophoretic
      patterns of SDS gels run in non-reducing conditions revealed a small group of
      antivenom proteins in 0.1 M DEAE cellulose fraction that was not found in 0.05 M,
      0.02 M, 0.25 M and 0.3 M NaCl ionic strength. Neutralizing activities to mapanare
      (Bothrops lanceolatus) venom have been already described but this is the first
      time that opossum serum anticrotalus activity is found. In spite of having
      preliminary results, we wish to make the corresponding report, while we
      accomplish the purification of the neutralizing component. One protein isolated
      from opossum serum or a synthetic peptide based on the aforementioned protein
      would probably be very useful in medical management of Crotalus vegrandis
      accidents.

PMID- 8993127
TI  - The spectre of drug resistant tuberculosis.

PMID- 8993128
TI  - Cytosolic calcium imaging by confocal laser scanning microscopy: applications in
      medicine.
AB  - Confocal microscopy is a valuable tool for analysing cell and tissue structure.
      Compared to conventional microscopic techniques, it has the advantages of
      increased image resolution and the capability for 3-D reconstruction. The
      introduction of ion-sensitive fluorescent probes has enabled second messenger
      systems to be studied in relation to cell physiology and function. The confocal
      laser scanning microscope (CLSM) is best suited for this purpose. Cytosolic
      calcium signalling with the CLSM has enhanced our understanding of calcium
      mediated signal transduction pathways. Given that calcium signalling plays a
      central role in cell in the mediation of cell functions, any aberration may
      induce pathological states.

PMID- 8993129
TI  - Contributions of various major causes of death to life expectancy in Singapore,
      1980-1990.
AB  - This paper considers the contributions by age of the various major groups of
      deaths to the increase in life expectancy at birth between 1980 and 1990 for both
      sexes in Singapore. Sixteen cause groups were used in the study. The data were
      analysed using LIFETIME, a personal computer package with a wide variety of
      methods for mortality investigations. Respiratory diseases made the largest
      contribution to the increase in life expectancy for both sexes. In contrast,
      ischaemic heart disease made a negative contribution of 1% in the gain in female
      life expectancy but contributed 12% improvement for males. Life tables for
      Singaporean males and females in the year 2000 were projected by extrapolating
      the mortality trends observed in earlier periods. The calculations show that the
      life expectancy at birth in the year 2000 to be 74.72 years for males and 79.48
      years for females.

PMID- 8993130
TI  - Myocardial infarction in patients aged 40 years and below: an angiographic
      review.
AB  - Over a period of 27 months, 32 patients aged 40 and below were admitted for acute
      myocardial infarction. Twenty-nine had coronary angiography with a mean of 15.7
      +/- 10.0 days following infarction. Fourteen patients had single vessel, 10 multi
      vessel and 5 had only minor coronary disease. Disease in the left anterior
      descending (LAD) artery was more common than in the circumflex or right coronary
      artery (RCA), but myocardial infarction occurred with near equal frequency in
      both the LAD and RCA territories. Only 2 infarct-related vessels were
      collateralized. Spontaneous coronary dissection was detected in 2 patients. The
      left ventricular function was significantly impaired in about half of the
      patients.

PMID- 8993131
TI  - Safety and efficacy of percutaneous Inoue-balloon mitral commissurotomy.
AB  - BACKGROUND: Although percutaneous transvenous mitral commissurotomy (PTMC) is
      currently accepted as the first-line treatment modality for selected patients
      with mitral stenosis, technical failures and the potential risk of inadvertent
      cardiac perforation with tamponade, resultant severe mitral regurgitation and
      death associated with the procedure continue to be important issues of concern.
      OBJECTIVES: The purpose of this study was to assess the safety profile and acute
      results of Inoue-balloon PTMC in a consecutive series of 50 patients with
      symptomatic significant mitral stenosis who underwent the procedure between
      January 1993 and August 1994. RESULTS: PTMC was successfully completed in all
      patients without encountering cardiac perforation, cardioembolism, severe (> or =
      grade 3+) angiographic mitral regurgitation or death. The mitral valve area
      increased from 0.8 +/- 0.2 cm2 to 1.7 +/- 0.4 cm2 (p = 0.0001) as assessed
      echocardiographically. Optimal results defined as a valve area improvement of >
      or = 50% and/or a final valve area of > or = 1.5 cm2 without significant mitral
      regurgitation (> or = 2 grade increase in mitral regurgitation or a final
      regurgitation > or = 3+) was obtained in 94% of patients. CONCLUSION: We confirm
      that Inoue-balloon PTMC is a safe and highly effective procedure as reflected by
      the absence of cardiac perforation, cardioembolism, severe mitral regurgitation
      or death and the excellent enlargement in mitral valve area. Furthermore, in our
      study the clinical restenosis rate was low with the majority of patients
      maintaining their improved functional status over a 14-month follow-up period.

PMID- 8993132
TI  - Severe noise-induced deafness--a 10-year review of cases.
AB  - Noise Induced Deafness (NID) is the leading occupational disease in Singapore.
      Every year, over 500 new cases of NID are detected by the Department of
      Industrial Health (DIH). Severe NID is a disabling disease which is compensable
      under the law. A retrospective study was conducted to elicit the profile of
      workers with severe, disabling NID. From 1 January 1985 to 31 December 1994, the
      DIH confirmed 127 of such cases. Of these, 57 (44.9%) were involved in the
      building and repair of ships and boats, 30 (23.6%) with the basic steel
      industries, manufacture and fabrication of metal products and storage batteries,
      9 (7.2%) with the transport and allied support industries, 7 (5.5%) in granite
      quarrying, 7 (5.5%) in the manufacture of food and drinks, 5 (3.9%) in the
      manufacture of wooden furniture and 7 (5.5%) in other industries such as
      manufacture of glass, electricity generation, construction, textiles, printing
      and so on. The mean age of these workers upon diagnosis of severe NID was 48
      years (SD 8.07). The mean duration of exposure to noise was 24 years (SD 9.11).
      The mean of the average hearing thresholds at 1, 2 and 3 kHz for these workers
      was found to be 61.5 dBA (SD 4.26). The main jobs at risk were grit blasters,
      steel workers, fitters, boiler fabricators, panel beaters and carpenters. Noise
      dosimetry was performed on 46 of the cases and the mean time-weighted exposure
      level was 90 dBA (SD 10.00). Finally, 82.7% of cases already had audiometric
      evidence of severe deafness at the time of notification.

PMID- 8993133
TI  - Clinical utility of a portable ultrasound scanner in the measurement of residual
      urine volume.
AB  - BACKGROUND: Post-voiding residual urine volume is an important investigation in
      the management of voiding dysfunction. Catheterisation is widely regarded as the
      "gold" standard method of measurement. We investigated the performance of a
      portable ultrasound scanner (Bladder Scan BVI-2500), as an alternative method of
      measurement. METHODS: This study was prospective in nature. One hundred
      measurements of post-voiding residual urine volume by ultrasound were compared
      with measurements by catheterisation. RESULTS: The mean absolute error of the
      scanner was 52 mL. For volumes below 200 mL and 100 mL, this was 36 mL and 24 mL
      respectively. A decision regarding whether to decompress the bladder by
      catheterisation would have also been correct in 86% to 89% of instances,
      depending on the cut-off value of the residual volume used. In other words, the
      ultrasound measurement would have been correct in 9 out of 10 clinical cases.
      CONCLUSION: We recommend the routine use of portable ultrasound scanners of
      similar accuracy in the measurement of post-voiding residual urine volume.

PMID- 8993134
TI  - Department audit of inpatient management of asthma.
AB  - Rising asthma morbidity and mortality worldwide has prompted the recommendation
      of guidelines for its management. There has also been recent interest in the role
      of medical audit in assessing the effectiveness of guidelines, and in identifying
      deficiencies in clinical practice. We disseminated guidelines for the inpatient
      management of asthma to our department in March 1994, and subsequently performed
      a criterion-based audit in which we measured our performance in fulfilling
      various criteria deemed essential for good asthma management. Three periods in
      time were audited: a five-week period in March/April 1993 before the existence of
      guidelines (n = 22), the same period in March/April 1994 (n = 27), and the month
      of August 1994 (n = 17). The introduction of guidelines resulted in definite
      improvement in history-taking, physical examination, management, review,
      monitoring and patient fulfillment of pre-discharge criteria. Specific
      deficiencies identified were underuse of peak flow measurements, which improved
      after guidelines; and under prescription of oxygen, which persisted despite the
      guidelines. No difference was noted in terms of the quality outcome indicators of
      length of hospital stay, complications of procedures, hospital incidents,
      morbidity, mortality or visits to the A & E. There was, however, an encouraging
      drop (although not statistically significant) in the one-month readmission rate
      from 13.6% in 1993, to 7.4% and 5.9% in 1994, after the introduction of
      guidelines.

PMID- 8993135
TI  - Severe community-acquired pneumonia in Singapore.
AB  - BACKGROUND: There has been no previous study documenting the aetiology and
      prognosis of severe community-acquired pneumonia in Singapore. Patients with
      severe community-acquired pneumonia (SCAP) needing admission to a medical
      intensive care unit in Singapore were studied retrospectively. METHODS: All
      patients admitted to the medical intensive care unit at National University
      Hospital from June 1991 to February 1993 with a diagnosis of community-acquired
      pneumonia were entered into the study. All patients had blood cultures, sputum
      cultures, serologies for Legionella and mycoplasma drawn on admission. APACHE II
      scores were determined prospectively. RESULTS: Fifty-nine consecutive cases from
      June 1991 to February 1993 were identified with a mean age of 61 (SD 17) years.
      Nearly all the cases needed mechanical ventilation (90%) and overall mortality
      was 63%. An aetiological agent was identified in the majority of cases (68%),
      with Klebsiella pneumoniae being the most common agent (9 cases, 15%).
      Haemophilus influenzae and Streptococcus pneumoniae were identified in 8% (5
      cases) and 5% (3 cases) of cases respectively. Pseudomonas pseudomallei was
      identified in 4 cases (7%) with a 100% mortality. Overall, gram-negative
      organisms were identified in 47% of cases. APACHE II was significantly higher in
      non-survivors. Age, creatinine levels, and the presence of bacteraemia were not
      prognostic features. CONCLUSION: SCAP in Singapore carries a high mortality with
      the predominance of gram-negative organisms. Empiric antibiotics should include
      gram-positive and gram-negative coverage with specific coverage for Pseudomonas
      pseudomallei.

PMID- 8993136
TI  - Two-dimensional and Doppler echocardiographic abnormalities in idiopathic
      dilatation of the pulmonary artery.
AB  - Although idiopathic dilatation of the pulmonary artery is uncommon, it requires
      to be distinguished from other important congenital heart diseases for which it
      may be confused clinically. We describe the two-dimensional (2D) and Doppler
      echocardiographic findings in two patients with this condition. Enlargement of
      the main pulmonary artery and right ventricle was demonstrated in both patients
      using 2D echocardiography. Pulmonary regurgitation was confirmed in Case 1 by
      both pulsed-Doppler echocardiographic and Doppler colour flow imaging studies and
      in Case 2 by microbubbles (which were generated from saline-injection into a
      peripheral vein) oscillating up and down across the pulmonary valve in systole
      and diastole respectively.

PMID- 8993137
TI  - Congenital abnormalities and pregestational diabetes mellitus in pregnancy.
AB  - Despite falling perinatal mortality rate, congenital malformation remains the
      major cause of mortality in infants of mothers with established diabetes. The
      perinatal mortality rate in this group of infants is 5 times the overall
      perinatal mortality rate in this hospital. It is well established that pre
      pregnancy counselling and maintenance of euglycaemia during the periconception
      period are the keys to prevention of congenital malformation. We are able to
      offer pre-pregnancy counselling to 29% of our diabetic mothers who are diagnosed
      to have pregestational diabetes mellitus only after the 6 weeks postnatal oral
      glucose tolerance test. Even in the known established diabetes mellitus, 95% of
      the patients were first seen after the period of organogenesis (> 8 weeks). This
      could explain our high congenital malformation rate of 15.7%.

PMID- 8993138
TI  - Is postnatal oral glucose tolerance testing necessary in all women with
      gestational diabetes.
AB  - Currently, women with gestational diabetes mellitus have a repeat oral glucose
      tolerance test 6 weeks after delivery to identify those with persistent glucose
      intolerance. In this study, 298 women with gestational diabetes had a postnatal
      oral glucose tolerance test and of these, 23.2% had persistent glucose
      intolerance after delivery. The aim of this study was to determine if the
      antenatal oral glucose tolerance test results could be used to predict which
      patients would have persistent glucose intolerance after delivery. If only those
      with severely abnormal antenatal results had persistent disease, then those with
      only mildly abnormal antenatal results could be spared the postnatal oral glucose
      tolerance test. Using receiver operator characteristic curves, this study showed
      that the antenatal oral glucose tolerance test results could not be used to
      predict reliably which patients would continue to have abnormal glucose tolerance
      postnatally. Hence, postnatal oral glucose tolerance testing of all patients with
      gestational diabetes is still necessary as the detection of persistent glucose
      intolerance is important for the control of the diabetic condition so as to
      minimise long-term complications.

PMID- 8993139
TI  - Case reports and mini review of bee stings of the cornea.
AB  - Bee stings of the eye are not uncommon. Quite a few clinical case reports have
      documented the various ocular reactions to the venom of the bee stings, which may
      range from mild conjunctivitis to sudden loss of vision. This report presents 2
      patients who suffered bee stings to the cornea and their different outcomes. The
      properties of bee venom as well as the treatment of various possible
      complications are also discussed.

PMID- 8993140
TI  - Factors affecting healing of below knee amputation.
AB  - Between January and December 1992, 54 diabetic patients with 60 below knee
      amputations performed in the Department of Orthopaedic Surgery O, Singapore
      General Hospital were available for evaluation. The average follow-up period was
      16.3 months with a range of 13 to 24 months. Five patients had stump necrosis and
      above knee amputation was performed. Eight patients had partial stump necrosis
      and required debridement with or without secondary procedures. The other patients
      had uneventful stump healing which was defined as healing of the stump wound
      without complications and remained intact for at least 6 months after surgery.
      Absence of popliteal pulse, presence of central cardiovascular disease and
      absence of intraoperative skin flap bleeding were found to be associated with
      higher incidence of stump necrosis.

PMID- 8993142
TI  - Cardiovascular reactivity in Malay Moslems during Ramadan.
AB  - The investigation examined the possibility that observance of Ramadan by Moslems
      in Malaysia is associated with modification of circulatory parameters.
      Cardiovascular reactivity was investigated employing the cold hand immersion test
      as the stressor stimulus. Resultant data showed increased blood pressures and
      vascular resistance during Ramadan in the absence of cold stimulus while the
      magnitude of the maximal cardiac and vascular response to the applied stressor
      which served as indicators of reactivity was not affected by the Ramadan
      situation.

PMID- 8993141
TI  - Holoprosencephaly and chromosomal anomalies.
AB  - Holoprosencephaly is a rare cerebral malformation resulting from failure or
      incomplete cleavage of the forebrain. The sonographic diagnosis consists of
      monoventricle, fused thalami and absent cavum septum pellucidi. Chromosomal
      anomalies, diabetes mellitus, alcohol, autosomal recessive inheritance and toxins
      have been implicated. We describe seven cases of holoprosencephaly diagnosed in
      the antenatal and postnatal periods. The chromosomal anomalies included trisomy
      13, triploidy, trisomy 13 with an unbalanced 13; 14 translocation and
      isochromosome of the long arm of 18. The clinicopathological findings and
      chromosomal anomalies are correlated.

PMID- 8993143
TI  - A Singapore study of obsessive compulsive disorder.
AB  - This is a study of 283 consecutive patients diagnosed as suffering from obsessive
      compulsive disorder (OCD) who had sought treatment in a private psychiatric
      clinic. This represents 4.5% of all patients treated in the clinic. Ninety-four
      percent were Chinese, 3% were Indians and 0.4% were Malays. The mean age of onset
      of illness was 27, SD 11.9. Fifty-one percent of patients developed their illness
      prior to age 25. There were more male than female patients. The male to female
      ratio was 1.4:1. A high percentage of patients had attained higher educational
      level and were economically active. The main forms of the obsession were idea,
      impulse and image; and the main contents were contamination, illness, aggression,
      exactness, sex, death and religion. The main compulsions were cleaning, checking,
      repetitive behaviour, need for symmetry and precision and hoarding. The co
      morbidity diagnoses were depressive, general anxiety, phobia, panic and psychotic
      disorder. In the patients who were followed-up for more than one year, it was
      found that 78% improved with treatment given. However, 22% remained unwell or
      deteriorated. In this series, it was noted that 17% of patients were severely
      incapacitated by the illness. Six percent had admission to mental hospital and 1%
      (3 cases) committed suicide.

PMID- 8993144
TI  - Modified barium swallow examination in dysphagic stroke patients.
AB  - Aspiration in dysphagic stroke patients is common and causes significant
      morbidity and mortality. Bedside clinical assessment of aspiration risk is often
      unreliable, particularly in patients with silent aspiration. Twenty-five
      dysphagic stroke patients clinically assessed to have borderline risk of
      aspiration were studied using a Modified Barium Swallow (MBS) examination. MBS
      revealed definite aspiration of liquids in 6 patients (24%) and semisolids in 4
      patients (16%). Combined clinical and MBS assessment revealed an additional 12
      patients (48%) had problems swallowing liquids and 5 patients (20%) semisolids
      due to reasons other than aspiration. In total, oral feeding of liquids were
      contraindicated in 18 patients (72%) and semisolids in 9 patients (36%). IN
      CONCLUSION: (1) In dysphagic stroke patients assessed clinically to have
      borderline risk of aspiration, MBS can distinguish those who aspirate from those
      who do not. MBS can also identify patients with other swallowing problems which
      expose them to potential aspiration. (2) Aspiration risk with food of various
      consistencies can be clearly defined, thus guiding the choice of food consistency
      and safe feeding methods.

PMID- 8993146
TI  - Global blindness and the nation.
AB  - In this presentation, the major causes of blindness and blindness according to
      geographical regions are considered. World blindness has become a global problem
      and is different in various regions of the Third World. The problems of the
      developing countries require individual solutions. Prevention of blindness in
      Singapore and around the region is considered from a local perspective. A
      national consciousness that involves every ophthalmologist is required, just as
      every individual has a contribution to make towards the prevention of blindness.

PMID- 8993145
TI  - The advance directive--a review.
AB  - The advance directive is a document that enables a competent individual to
      specify the form of health care he would like to have, in the event that he is
      unable to make such decisions in the future. This review paper traces the
      development of the advance directive from 1967, when it was first proposed by
      Luis Kutner. The Karen Ann Quinlan case and the Nancy Cruzan case are cited as
      examples of the case for the advance directive. The argument is that advance
      directives assist doctors, patients, family members and other carers with the
      increasingly complex health care decision making. Reservations have been
      expressed about the anticipatory nature of the decision, possible conflict with
      personal and religious ethics and the risk of cost containment considerations
      being over-riding concerns. The advance directive in America has undergone
      changes since the California Natural Death Act 1976 was passed. In the 1980s,
      "terminal" included permanent unconsciousness and advanced dementia. The
      declarant was also given a wider choice of treatment procedures that they wish to
      be withheld. Proxy directives were also introduced. In the 1990s, the declarant
      is even allowed to request the use of life-prolonging procedures. When
      appropriately implemented, the advance directive can perform its intended
      functions of clarifying the patient's perspective on life, death and medical
      care. When it is vague in terminology or applied to patients with uncertain
      prognoses, it can cause confusion to the patient's carers; and when improperly
      used, it can become an instrument not of patient's preferences, but of economic
      purpose, family bias, or physician's values.

PMID- 8993147
TI  - Priorities in neonatal care in developing countries.
AB  - Lower perinatal and neonatal mortality have been achieved in the developed
      countries following advancement of neonatal care, introduction of high
      technologies, and better knowledge of pathophysiology of the newborn infants.
      Other contributing factors are organised delivery room care with skillful
      resuscitative techniques as well as risk identification and efficient transport
      of the sick infants including in utero transfer of the fetus, etc. It cannot be
      assumed that similar results can be attained in developing countries where
      financial and human resources are the problems. With limited resources, it is
      necessary to prioritize neonatal care in the developing countries. It is
      essential to collect minimum meaningful perinatal data to define the problems of
      each individual country. This is crucial for monitoring, auditing, evaluation,
      and planning of perinatal health care of the country. The definition and
      terminology in perinatology should also be uniform and standardised for
      comparative studies. Paediatricians should be well trained in resuscitation and
      stabilisation of the newborn infants. Resuscitation should begin in the delivery
      room and a resuscitation team should be formed. This is the best way to curtail
      complication and morbidity of asphyxiated births. Nosocomial infections have been
      the leading cause of neonatal deaths. It is of paramount importance to prevent
      infections in the nursery. Staff working in the nursery should pay attention to
      usage of sterilised equipment, isolation of infected babies and aseptic
      procedures. Paediatricians should avoid indiscriminate use of antibiotics. Most
      important of all, hand-washing before examination of the baby is mandatory and
      should be strictly adhered to. Other simpler measures include warming devices for
      maintenance of body temperature of the newborn babies, blood glucose monitoring,
      and antenatal steroid for mothers in premature labour. In countries where
      neonatal jaundice is prevalent, effective management to prevent kernicterus is
      essential. Simple assisted ventilatory device such as nasal continuous positive
      airway pressure (nCPAP) is also useful.

PMID- 8993148
TI  - Working party report of the Gastroenterological Society of Singapore. Part II-
      Helicobacter pylori and non-ulcer dyspepsia in Singapore.
AB  - Non-ulcer dyspepsia (NUD) is a common symptom whose cause is currently unclear.
      Helicobacter pylori (H pylori) infection is found in half of all patients with
      NUD but other pathophysiological abnormalities eg delayed gastric emptying, have
      also been described. NUD patients with or without H pylori infection have
      identical symptom patterns and pathophysiological parameters. Studies on the
      efficacy of H pylori treatment in NUD give equivocal results to date. We
      therefore do not recommend treatment for H pylori in NUD.

PMID- 8993149
TI  - Clinics in diagnostic imaging (15). Carotid body tumour.
AB  - A 30-year-old Chinese woman presented with an enlarging pulsatile swelling in the
      left neck. A similar right neck mass was excised 2 years previously. Digital
      subtraction angiography showed a well-defined, hypervascular tumour situated at
      the left common carotid arterial bifurcation, typical of a carotid body tumour.
      Complete resection of the second carotid body tumour was achieved. The clinical
      and imaging features of this tumour are described.

PMID- 8993150
TI  - Clinics in diagnostic imaging (16). Lower gastrointestinal bleeding caused by
      ileal tumour.
AB  - A 38-year-old Chinese man presented with melaena and anaemia. Urgent superior
      mesenteric angiogram showed a well-circumscribed vascular mass in the ileum. A
      stromal tumour was surgically excised. The radiological approach to lower
      gastrointestinal bleeding is described, followed by a brief discussion on stromal
      tumours of the small bowel.

PMID- 8993151
TI  - Cutaneous gangrene secondary to metastatic calcification in end stage renal
      failure--a case report.
AB  - Metastatic calcification is a frequent association of chronic renal failure but
      skin involvement is accepted as a rare, albeit well recognised, complication
      accompanying the secondary hyperparathyroidism that results from renal
      impairment, although the aetiology remains unknown. Skin involvement can take the
      form of metastatic calcinosis cutis or cutaneous gangrene resulting from vascular
      calcification. There have been reported cases which describe the healing of
      gangrenous areas following parathyroidectomy as well as use of dietary
      restriction of phosphorus and phosphate binding antacids(1-6). We report a case
      of a 35-year-old man with end stage renal failure who presented with cutaneous
      gangrene but who eventually succumbed despite a subtotal parathyroidectomy and
      review some of the literature concerning this subject.

PMID- 8993152
TI  - Intracranial germinoma metastasizing via a ventriculo-peritoneal shunt.
AB  - Primary germinomas of the central nervous system carry a good prognosis because
      of their radiosensitivity. Recurrences are rare and extraneural metastases are
      even more unusual. One of the possible routes of extraneural spread is via
      ventriculo-peritoneal shunts which may be required to reduce intracranial
      pressure. One such case of germinoma metastasizing via a ventriculo-peritoneal
      shunt is reported. Patients with intracranial germinomas and ventriculo
      peritoneal shunts should have close surveillance of their abdomens and may
      require systemic chemotherapy.

PMID- 8993153
TI  - Popliteal artery pseudoaneurysm caused by an osteochondroma--a traditional
      medicine massage sequelae.
AB  - We report an unusual case of a popliteal aneurysm complicating a distal femoral
      osteochondroma caused by the repeated massages of a traditional medicine
      practitioner (sinseh). Management was by excision of the exostosis and
      reconstruction of the damaged arterial segment by a reversed long saphenous vein
      graft. We advice against massage over an osteochondroma on the distal medial
      aspect of the femur and suggest prophylactic removal of such lesions because of
      this potential complication.

PMID- 8993154
TI  - The syndrome of painful legs and moving toes--a case report.
AB  - The syndrome of painful legs and moving toes is an uncommon and distressing
      condition with pain in the feet or legs and involuntary movements of the toes. It
      can follow spinal cord or cauda equina trauma, lumbar radiculopathy, injury to
      the feet, peripheral neuropathy or without any preceding causes. Ephaptic
      transmission in damaged nerve roots or peripheral nerves with central
      reorganisation may be the underlying mechanism of the syndrome. Treatment is
      difficult. We report a case of this syndrome following peripheral neuropathy,
      with a good early response to the GABA agonists baclofen and clonazepam. The role
      of different GABA agonists in the treatment of this condition needs to be better
      defined.

PMID- 8993156
TI  - The taxonomy of lysosomes and related structures.

PMID- 8993155
TI  - Mania following left hemisphere injury.
AB  - A case of mania following closed head injury to the left hemisphere is reported.
      The patient presented with a self-limiting manic episode that recovered without
      treatment. It is postulated that the head injury is the causative factor in this
      case. This was supported by laboratory results as well as psychological
      investigations. It is believed that non-dominant right hemisphere injury is
      related to the development of mania. However, a search of the literature revealed
      five other cases of mania following left hemispheric injury. Although the
      mechanisms implicated in the pathogenesis of secondary mania have not been
      established, this case adds to the growing evidence that head injury may be
      directly causative in affective psychoses. Therefore, it is premature to conclude
      that mania is a pathology of the non-dominant right hemisphere.

PMID- 8993157
TI  - Origin of lysosomal proteins.

PMID- 8993158
TI  - Endocytosis.

PMID- 8993159
TI  - Autophagy.

PMID- 8993161
TI  - Lysosomal metabolism of proteins.

PMID- 8993160
TI  - Selective proteolysis: 70-kDa heat-shock protein and ubiquitin-dependent
      mechanisms?

PMID- 8993162
TI  - Lysosomal metabolism of glycoconjugates.

PMID- 8993163
TI  - Lysosomal metabolism of lipids.

PMID- 8993164
TI  - Lysosomal nucleic acid and phosphate metabolism and related metabolic reactions.

PMID- 8993165
TI  - Acidification of lysosomes and endosomes.
AB  - Lysosomes, endosomes, and a variety of other intracellular organelles are
      acidified by a family of unique proton pumps, termed the vacuolar H(+)-ATPases,
      that are evolutionarily related to bacterial membrane proton pumps and the F1-F0
      H(+)-ATPases that catalyze ATP synthesis in mitochondria and chloroplasts. The
      electrogenic vacuolar H(+)-ATPase is responsible for generating electrical and
      chemical gradients across organelle membranes with the magnitude of these
      gradients ultimately determined by both proton pump regulatory mechanisms and,
      more importantly, associated ion and organic solute transporters located in
      vesicle membranes. Analogous to Na+, K(+)-ATPase on the cell membrane, the
      vacuolar proton pump not only acidifies the vesicle interior but provides a
      potential energy source for driving a variety of coupled transporters, many of
      them unique to specific organelles. Although the basic mechanism for organelle
      acidification is now well understood, it is already apparent that there are many
      differences in both the function of the proton pump and the associated
      transporters in different organelles and different cell types. These differences
      and their physiologic and pathophysiologic implications are exciting areas for
      future investigation.

PMID- 8993167
TI  - Lysosome pharmacology and toxicology.

PMID- 8993166
TI  - Metabolite efflux and influx across the lysosome membrane.

PMID- 8993168
TI  - Diagnosis of childhood tuberculosis by polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) using oligonucleotides based on the
      repetitive sequence (IS6110) of Mycobacterium tuberculosis as a primer was
      evaluated for detection of M.tuberculosis in clinical samples. We tested 55
      clinical specimens from patients suspected of having tuberculosis and 71
      specimens from control subjects. PCR was more sensitive than culture (positivity
      rate was 14.5% and 36.3%, respectively, in suspected patients). This approach to
      the diagnosis of tuberculosis is a valid diagnostic alternative to classical
      procedures.

PMID- 8993169
TI  - Microorganisms involved in acute bacterial meningitis in children and the role of
      Haemophilus influenzae.
AB  - Acute bacterial meningitis (ABM) is an important cause of mortality and
      neurological damage in children. Documentation of the etiological agents is very
      important both for the treatment of patients and for prophylactic approaches.
      H.influenzae, N.meningitidis and S.pneumoniae are the three major pathogens
      involved in ABM. In Turkey for many years H.influenzae has not been isolated in
      cerebrospinal fluid (CSF) specimens. In order to show the bacteria involved in
      ABM in our hospital and to see the role of H.influenzae, we investigated the CSF
      of 59 patients with bacterial meningitis using Gram and Wayson stains, culture
      and latex agglutination techniques. The agents were determined in 38 (64.4%)
      specimens by using culture positivity in 30 (50.8%), and latex or stain
      positivity in eight (13.6%) specimens. The microorganisms causing ABM included
      S.pneumoniae (25.6%), gram-negative enteric bacillI (17.9%), N.meningitis
      (12.8%), alpha hemolytic streptococci (10.3%), H.influenzae (10.3%),
      nonfermentative gram-negative bacillI (5.1%), candida spp. (5.1%), group B
      streptococci (2.6%), coagulase negative staphylococci (2.6%), S.aureus (2.6%) and
      pseudomonas spp. (5.1%). In this study it has been shown that H.influenzae can
      cause ABM in Turkish children. Multicentric studies from different parts of
      Turkey will be helpful in showing the real incidence in our country.

PMID- 8993170
TI  - A linkage analysis in two families with bilateral retinoblastoma.
AB  - Using polymerase chain reaction (PCR) amplification from blood samples, Xbal and
      BamHI polymorphisms were analyzed in two families with bilateral retinoblastoma.
      In one of the families it was predicted using the BamHI polymorphism that the 200
      bp allele co-segregates with the disease. This family was uninformative for Xbal
      polymorphism. The second family was uninformative for both Xbal and BamHI
      polymorphism.

PMID- 8993171
TI  - Effects of methylprednisolone pulse therapy on insulin injections in patients
      with insulin-dependent diabetes mellitus.
AB  - In this study we evaluated 31 insulin-dependent diabetes mellitus (IDDM) patients
      (ages 12.1 +/- 3.4 years, 18 males/13 females) who started on multiple
      subcutaneous insulin injections (MSII) within six weeks of diagnosis and achieved
      either complete (CR: no insulin requirement and near-normoglycemia for at least
      two weeks) or incomplete (ICR: minimum 50% decline in insulin requirement while
      maintaining near-normoglycemia for two weeks or more) remissions within the first
      12 weeks of the MSII trial. Methylprednisolone pulse therapy (MP) was
      administered four times per day by i.v. bolus at a dose of 30 mg/kg (max. 1000
      mg) on alternative days. Eleven patients did not accept "MP-pulse" therapy;
      therefore, we followed these cases (7 males/4 females) as the control group.
      During the first year of follow-up, 13 patients from the "MP pulse" group
      achieved CR (3 males/1 female) or ICR (5 males/4 females) in 3.5 to 14 months.
      Remission occurred in only two of the control group cases (1 male CR for 17 days
      and 1 female CR for 7 months). Of those with CR in the "MP-pulse" and control
      groups, all were greater than 12 years of age, and all but one in the "MP-pulse"
      group were males. The stimulation capacity of beta cells (as defined by
      percentage increase in serum C-peptide levels after glucagon injection) among CR
      cases was found to be higher than that of non-remitted (NR) cases (p < 0.05 at
      onset, p < 0.001 during MSII-induced remission and p < 0.05 at the end of the
      first year of follow-up). Although patients with CR or ICR had higher beta cell
      reserves than NR cases at onset, only CR cases could sustain this capacity during
      the MSII-induced remission phase and one year after "MP-pulse" therapy. From this
      preliminary study, we conclude that "MP-pulse" therapy, may lead to prolonged
      near-normal beta cell function or partly preserved residual beta cell reserve
      during the MSII-induced remission phase of IDDM, The beneficial effects of MP
      could be seen clearly in patients diagnosed during the late childhood years.

PMID- 8993172
TI  - Relation between limited joint mobility and peripheral nerve function in diabetic
      children.
AB  - In order to assess the relation between limited joint mobility (LJM) and
      peripheral nerve function in diabetic children, peroneal nerve amplitude and
      motor conduction velocity as well as sural nerve amplitude and distal latency
      were measured with a Medelec MSG electromyograph. LJM was examined by observing
      the hands in the prayer position of 60 unselected diabetic children (average age
      11.2 +/- 3.1 years; mean duration of diabetes 4.1 +/- 3 years) and 31 healthy
      controls. Of 60 patients, 38.3 percent had limited joint mobility. no influence
      of sex on expression of LJM was found. Its appearance was influenced by age,
      duration of diabetes and metabolic control (HbA1c) (p < 0.001, p < 0.001, p <
      0.001, respectively). The mean amplitude, nerve conduction velocity and distal
      latency values in diabetic children with LJM were slower than those in the normal
      control group (peroneal amplitude p < 0.01), peroneal MCV p < 0.001, sural
      amplitude p < 0.001, sural distal latency p < 0.001). Of four patients with stage
      IV LJM, three had symptomatic neuropathy diagnosed using the criteria suggested
      by Dyck. Consequently, LJM identifies a population at risk for development of
      diabetic neuropathy. Thus, being easy and sensitive, LJM determination may
      provide both the physician and the patient himself with an important motivation
      to improve diabetic control in an effort to prevent diabetic neuropathy.

PMID- 8993173
TI  - Relationship between maternal and neonatal iron stores.
AB  - In this study, hemoglobin (Hb), mean corpuscular volume (MCV) and serum ferritin
      (SF) levels were measured in 76 neonates and their mothers at delivery. Infants
      were grouped according to their gestational ages. Group I (< 34 weeks), group II
      (34-37 weeks) and group III (> 37 weeks) consisted of 15, 33 and 28 infants,
      respectively. Blood studies were repeated at two months of age in 50 neonates (26
      from group II and 24 from group III). Among the three groups of infants, SF
      levels were lowest in group I, and among mothers, Group III had the lowest
      levels. There were positive correlations between maternal and neonatal SF levels
      in groups II and III. There was no difference between the SF levels of neonates
      born to mothers with depleted or adequate iron stores. Anemia with a normal SF
      level was present in 14.4 percent, subclinic iron deficiency (normal Hb and low
      SF level) in 11 percent and iron deficiency anemia (low Hb and low SF levels) in
      7.8 percent of the mothers. At two months of age 38.4 percent of preterm and 16.6
      percent of term infants had Hb concentrations less than 10 g/dl. Only one of
      these infants had a low SF level. There was a negative correlation between
      maternal SF levels and the Hb concentration of term infants at two months of age.

PMID- 8993175
TI  - Blade atrial septostomy: experience with 18 patients.
AB  - Blade atrial septostomy was performed in 18 patients, including 14 with
      transposition of the great arteries, three with tricuspid atresia and one with
      severe mitral stenosis and ventricular septal defect. The patients' ages ranged
      from 25 to 210 days (mean: 108 +/- 64 days), and weights ranged from 3.0 to 6.0
      kg. Following blade septostomy, partial arterial pressure of oxygen (PaO2)
      increased from an average of 22 +/- 3.3 mmHg to 38.9 +/- 7.6 mmHg (p < 0.001),
      and prompt clinical improvement was observed in the majority of patients.
      Significantly decreased atrial pressures (from 8.16 +/- 6.1 to 3.93 +/- 2.2 mmHg,
      p < 0.01) and significantly enlarged inter-atrial openings (from 1.6 +/- 0.9 to
      7.5 +/- 1.8 mm, p < 0.001) were achieved with successful blade atrial septostomy.
      Blade atrial septostomy is an effective and life-saving procedure in patients who
      require nonrestrictive inter-atrial communication.

PMID- 8993174
TI  - The relationship between Apgar score and umbilical arterial blood gas values in
      newborns.
AB  - The data for this report were derived from 61 newborns and their mothers. Of the
      newborns 45.9 percent had one-minute Apgar scores of less than seven, and 54.1
      percent had Apgar scores of seven or greater. The five-minute Apgar score was
      less than 7 in 6.6 percent of cases. While 23 percent of newborns had pH values
      of less than 7.20, 77 percent had pH of 7.20 or greater. Only 39.3 percent of the
      28 newborns with one-minute Apgar score of less than 7 and 75 percent of the four
      newborns with five minute Apgar scores of less than 7 had pH values less than
      7.20. Of 33 newborns, 9.1 percent who had Apgar scores of seven or more had pH of
      less than 7.20. We determined the sensitivity of the one minute Apgar score in
      acidemia to be 78 percent, the specificity to be 63 percent, the positive
      predictive value as 39 percent, and the negative predictive value as 90 percent.
      The one minute score is very poor for detecting acidosis when present but is
      rarely misleading when acidosis is absent. There was a positive correlation
      between the Apgar score and pH (p < 0.001). The best correlation with umbilical
      artery pH values was observed with base excess (-BE) values (p < 0.001). Severe
      acidosis (pH < 7.11) was detected in eight cases. As delta pH increases, pH, pO2
      and HCO3 decrease and pCO2 increases. Of 11 infants with delta pH > or = 0.20,
      63.6 percent were sick infants and only one (9%) had normal Apgar scores.

PMID- 8993176
TI  - Radiofrequency catheter ablation of accessory pathways and modification of
      atrioventricular node in children and adolescents.
AB  - Catheter ablation of an accessory pathway and atrioventricular node modification
      using 550 kHz radiofrequency was attempted in 23 children and adolescents between
      five and 19 years of age (mean = 15.7 years). Fifteen children had accessory
      pathway-mediated tachycardia and eight had atrioventricular node reentrant
      tachycardia. Accessory pathways were present in ten children. Two patients had
      associated congenital heart disease. Symptoms included disabling palpitations and
      episodes of syncope. Ablation was attempted from the right and left sides of the
      heart. Single-catheter technique was used in seven patients. Eleven of the 15
      patients with accessory pathways were treated completely. Two patients had
      recurrences, and one of them died after the arrhythmia surgery. There were two
      failures. Two patients with incomplete interruption of the accessory pathways
      were followed up clinically. There were three cases with temporary systemic
      embolization and one with severe pain related to radiofrequency energy
      application. Atrioventricular node modification was done by fast-pathway ablation
      in six, and by slow-pathway ablation in two patients. Two patients with fast
      pathway ablation had recurrences of clinical arrhythmia, and one of them
      underwent a successful second session. There were no complications associated
      with the procedure in this group of patients. Radiofrequency catheter application
      was initially successful in 21 (84%) out of 25 procedures, and ultimately
      curative in 16 (69%) out of 23 patients. There were some serious complications
      which resolved in the immediate post-procedure period. Radiofrequency catheter
      ablation appears to be a safe and successful method for the management of
      supraventricular tachycardia secondary to accessory pathways or atrioventricular
      node reentrant tachycardia in children and adolescents.

PMID- 8993177
TI  - Peripheral and nasal eosinophilia and serum total immunoglobulin E levels in
      children with ascariasis.
AB  - In order to evaluate peripheral and nasal eosinophilia and serum total IgE levels
      in ascariasis, 30 children between two and 12 years of age whose fecal samples
      were found to contain Ascaris lumbricoides, and 30 children between 1.5 and 12
      years of age who did not have ascaris in their fecal samples, were enrolled in
      the study. Peripheral eosinophil counts and serum total IgE levels were
      significantly higher in the study group, but there was no significant difference
      between the nasal eosinophil counts of the two groups. Since total serum IgE
      levels differ according to age, the patients and the control groups were also
      evaluated within three age-groups. Peripheral eosinophil counts and serum total
      IgE levels of patients with ascariasis in all age ranges were significantly
      higher, but nasal eosinophil values did not differ significantly. These results
      show that in ascariasia the presence of peripheral eosinophilia and high total
      serum IgE levels are similar to those in atopic diseases, and some allergic
      symptoms such as nasal itching can be caused by parasites. However, nasal itching
      does not correlate with nasal eosinophilia in ascariasis. This is an important
      feature in the differential diagnosis.

PMID- 8993178
TI  - N-acetyl-beta-D-glucosaminidase excretion in patients with unilateral renal
      agenesis or nephrectomy in childhood.
AB  - Renal functional impairment due to the damaging effect of hyperfiltration of the
      remnant kidney was evaluated in patients who had been uninephrectomized in
      childhood or had unilateral agenesis. Sixteen patients (8 male, 8 female) a mean
      of 7.1 years (1-26 years) postnephrectomy were evaluated. Blood pressure values,
      clearances of creatinine (Ccr) and phosphorus (Cp), urine osmolality, total
      protein excretion and NAG (N-acetyl-beta-d-glucosaminidase) excretion were
      determined. Ccr values were slightly but not significantly lower (90.390 +/-
      11.223 ml/min) than those of control subjects (110.818 +/- 7.755 ml/min). Daily
      urinary protein excretion adjusted for body surface was significantly higher in
      the study group (p < 0.05). Urinary NAG excretion measured with a
      spectrophotometric method and described as the Cr ratio was significantly higher
      in the patients than the control subjects (p < 0.05). It was concluded that the
      damaging effects of hyperperfusion not only involve the glomerulus but also the
      proximal and distal tubulus.

PMID- 8993179
TI  - Serum erythropoietin and granulocyte-macrophage-colony stimulating factor levels
      with megadose methylprednisolone treatment.
AB  - Serum erythropoietin (EPO) and granulocyte-macrophage-colony stimulating factor
      (GM-CSF) levels were determined in 12 children with acute and seven with chronic
      idiopathic thrombocytopenic purpura (ITP) prior to and during megadose
      methylprednisolone (MDMP) treatment by using enzyme-linked immunosorbant assay
      (ELISA) kits. It was shown that elevation of EPO and GM-CSF levels was correlated
      with an increase in hemoglobin (Hb), packed cell volume (PCV), red blood cell
      (RBC), leukocyte (Leu), polymorphonuclear leukocyte (PMN) and monocyte (Mo)
      counts during MDMP treatment.

PMID- 8993180
TI  - RFLP discordance in a PKU family due to a deletion in the PAH gene.
AB  - We have previously reported preliminary data on a PKU family showing a discordant
      segregation of Pvu II (b) alleles at the PAH locus. A combination of several
      restriction enzymes and probe C2.6 (Intron 2) as well as STR typing were used to
      dissect the molecular structure of the PAH gene around exon 3. In this family,
      the results of this analysis and a re-examination of the physical map of the 5'
      end of the gene provided strong evidence for the occurrence of a deletion
      removing exon 3. The "Sicilian" (approximately 2.5 kb) and "Yemenite Jew" (6.7
      kb) deletions, the latter one also deleting exon 3, are different in terms of
      both the 5'-end breakpoint and apparent length. This study, besides adding a new
      member to the long and increasing list of nearly 200 PAH gene mutations, also
      proposes to undertake a careful evaluation of RFLP discordances incidentally
      detected at the PAH locus.

PMID- 8993181
TI  - Fever and altered consciousness are not always equal to central nervous system
      infection: neuroleptic malignant syndrome in a 15-year-old girl.
AB  - Neuroleptic malignant syndrome, the most serious and potentially fatal side
      effect of neuroleptics, is characterized by altered consciousness, extrapyramidal
      symptoms, hyperthermia, elevated plasma creatine phosphoidnase and leukocytosis.
      In the child and adolescent population, the syndrome may be underrecognized or
      underreported. We describe a 15-year-old girl who developed neuroleptic malignant
      syndrome after a single injection of two different neuroleptics. We find the case
      interesting because the patient's course was unusual, and she was treated
      successfully with the combination of diazepam and biperiden. Our aim is to
      discuss several aspects of the syndrome through this case, particularly the
      problem of recognition.

PMID- 8993182
TI  - Hepatic mucormycosis in a child with fulminant hepatic failure.
AB  - Mucormycosis is an uncommon, opportunistic infection in children. We present a
      case of fulminant hepatic failure with hepatic mucormycosis. Although the
      suggested defects and pathogenic mechanisms in infections related to hepatic
      failure and mucormycosis are similar, few cases with both mucormycosis and liver
      failure have been reported.

PMID- 8993183
TI  - Balloon dilatation angioplasty of a stenotic Blalock-Taussig anastomosis. A case
      report.
AB  - A 12-year-old boy with tetralogy of Fallot was evaluated for increasing cyanosis
      and exercise intolerance. The patient had a right Blalock-Taussig shunt operation
      11 years previously and a left modified Blalock-Taussig shunt operation one year
      previously. After demonstration of hypoplastic pulmonary arteries, the stenosed
      right Blalock-Taussig shunt and the totally occluded, left modified Blalock
      Taussig shunt were successfully dilated with a 7-mm-diameter angioplasty balloon
      resulting in a 5-mm-diameter patent shunt. We believe that, when possible,
      balloon dilatation angioplasty of stenosed Blalock-Taussig shunts is a reasonable
      and safe alternative to surgery.

PMID- 8993184
TI  - Acute alternating hemiplegia. A case report.
AB  - Acute alternating hemiplegia in childhood is a rare disorder characterized by
      onset before 18 months of age and frequent attacks of alternating paralysis. In
      this case report, a 20-month-old boy having the diagnosis of acute alternating
      hemiplegia is presented. The diagnosis was based on clinical features. The
      frequency and severity of the hemiplegic attacks decreased following flunarizine
      therapy. In this case, cerebral perfusion was investigated during ictal and
      interictal periods. Tc-99m HMPAO-Brain single photon emission computed tomography
      (SPECT) revealed normal cerebral perfusion in ictal periods and hypoperfusion in
      interictal periods.

PMID- 8993185
TI  - Infantile myofibromatosis: a case with unusual features and review of the
      literature.
AB  - A three-month-old boy was admitted for a slowly progressing nodule in his right
      chin, first recognized at birth and recently accompanied by facial paralysis. It
      was found to be a soft tissue mass arising in subcutaneous tissue and extending
      deep into the temporal muscle, causing temporal bone erosion without infiltrating
      the dura. Initially interpreted as mesenchymal chondrosarcoma, combined
      chemotherapy (PULSE-VAC) was given. Eighteen months later an additional nodule
      developed in the paraspinal skin. Evaluation of both lesions showed vimentin and
      alpha-smooth-muscle-action positivity. As the final diagnosis was multicentric
      infantile myofibromatosis, the child was followed up without therapy. Thirty
      months later, multiple osteolytic lesions appeared on the skull and long bones of
      the extremities. Some lesions remained stable and some regressed during two years
      of follow-up.

PMID- 8993186
TI  - Hypothalamic hamartoma with gelastic epilepsy, precocious puberty and
      polydactyly.
AB  - An entity including gelastic epilepsy, precocious puberty, polydactyly and a
      hypothalamic hamartoma type IIa is described in a 16-year-old female patient.
      Polydactyly was detected at birth, she developed precocious puberty at four years
      of age, and gelastic epilepsy was diagnosed at age seven. The precocious puberty
      was successfully treated medically and her treatment was discontinued at the age
      of 10 years, but the gelastic seizures were difficult to control. When the
      patient was 11 years old, MRI revealed a hypothalamic hamartoma. The combination
      of these four features is very rare in the literature.

PMID- 8993187
TI  - Tricho-rhino-phalangeal syndrome type I.
AB  - Tricho-rhino-phalangeal syndrome type I (TRPS I) is characterized by a bulbous
      nose, sparse hair and epiphyseal coning. Autosomal dominant and recessive
      transmission are suggested. The presence of cone-shaped epiphyses, the major
      complaint of patients due to swelling over the phalangeal joints, requires
      differential diagnosis among various syndromes. This paper, describing a ten-year
      old girl with TRPS I, aims to bring the features of the syndrome to medical
      attention.

PMID- 8993191
TI  - Good medicine.

PMID- 8993188
TI  - [Incisional hernia. A study of morbidity, mortality and bed utilization in a
      Danish county].
AB  - Four hundred and four patients operated for ventral hernia during a five year
      period were reviewed with special emphasis on morbidity, mortality and number of
      days in hospital. The patients were divided into 357 patients who had been
      operated for ventral hernia only once (A) and 47 patients who had been operated
      more than once for ventral hernia (B). There were no significant differences
      between the two groups regarding to ages or preoperative condition. The
      postoperative complications were 21% in group A and 12% in group B, although this
      was not statistically significant. Of those who suffered a complication after the
      operation, 76% had a competing illness prior to the operation. The overall
      mortality was 0.5%. The patients were hospitalized for a total of 4846 days. In
      view of the results of this material and of the high recurrence rate demonstrated
      in the literature, a restrictive attitude towards operations for ventral hernia
      is recommended.

PMID- 8993192
TI  - Your memory/your patient's memory and your medical records.

PMID- 8993193
TI  - Ten rules of civility for the medical warrior.

PMID- 8993194
TI  - Atypical presentation of a dermoid brain cyst.
AB  - This article describes the case of a dermoid cyst with unique radiological
      findings in an unusual location. This cyst arose from the anterior clinoid
      process and projected into the right frontal lobe in a 39-year-old man. CT and
      MRI revealed a gravity dependent level within this low density lesion.
      Stereotaxic biopsy revealed that this gravity dependent level was formed between
      layers of fat and fluid. Craniotomy later showed the presence of hair within this
      lesion. The literature concerning the radiographic findings and location of
      dermoid brain cysts is also reviewed.

PMID- 8993196
TI  - Injuries related to logging: epidemiology, etiology and implications for
      prevention.
AB  - This article describes our study of 36 male patients who were brought to Ruby
      Memorial Hospital in Morgantown for treatment of non-fatal logging-related
      injuries. The type and severity of their injuries is described, as well as the
      host, vehicular/mechanical and environmental factors contributing to the
      injuries. The suggestions of the patients on how to prevent their injuries are
      compared to existing OSHA standards.

PMID- 8993195
TI  - Autoimmune hepatitis in children.
AB  - Autoimmune hepatitis (AIH) is usually diagnosed after other viral, metabolic or
      drug-induced etiologies have been ruled out. Although uncommon in children, the
      disease can manifest itself with severe hepatocellular damage and early fibrosis.
      Early diagnosis and aggressive treatment may improve morbidity and decrease
      mortality. In other cases, liver transplantation is the final rescue for these
      children. We describe our experience with five children who were diagnosed with
      autoimmune hepatitis. Their diagnosis, medical treatment and clinical outcome are
      presented with a review of the literature.

PMID- 8993197
TI  - Sir William Macewen's visit to California as the First Lane Medical Lecturer. A
      centennial celebration.
AB  - 1996 marked the centennial anniversary of the 1896 visit to California of William
      Macewen, MD, Regius Professor of Surgery of the University of Glasgow, Scotland,
      to give the first Lane Medical Lectures. I describe the origins of this historic
      lecture series and include photographic records. The progress and development of
      modern California medicine have been greatly influenced by the personalities who
      initiated and nurtured this lecture series.

PMID- 8993198
TI  - Serious mushroom poisonings in California requiring hospital admission, 1990
      through 1994.
AB  - Hunting and consuming wild mushrooms is an increasingly popular avocation, as
      well as a means of subsistence for certain groups in the United States. Consuming
      wild mushrooms is relatively safe for persons with the necessary expert
      knowledge. Each year, however, tragic deaths or illnesses occur when unsuspecting
      persons ingest toxic mushrooms. We conjectured that there may be vulnerable
      subgroups that should be targeted for public service announcements and education
      about mushrooms. Therefore, we reviewed California's hospital discharge database
      from 1990 through 1994 to ascertain demographic characteristics and outcomes of
      "serious" mushroom exposures requiring a hospital admission. Children younger
      than 5 years have a higher rate of hospital admission for "serious" poisonings.
      Therefore, parents should be reminded of the need for supervising children in
      areas with wild mushrooms. We did not find evidence that poisoning rates differed
      significantly between ethnic or racial groups, but this finding may be limited by
      a failure of these groups to seek care after becoming ill. We discuss briefly the
      symptoms and treatment of cases of possibly lethal ingestion of amatoxin
      containing species of mushrooms.

PMID- 8993199
TI  - Evaluation of cerebrospinal fluid in Southeast Asian refugees with reactive
      serologic tests for syphilis.
AB  - To determine the prevalence of cerebrospinal fluid abnormalities in Southeast
      Asian refugees with reactive serologic tests for syphilis, we evaluated 65
      patients, 36 prospectively and 29 retrospectively, in a primary care clinic.
      Information was collected on history of treponemal infections, neurologic
      symptoms and signs, and total protein concentration, leukocyte count, and the
      VDRL test in the cerebrospinal fluid. Neurologic symptoms were reported by all
      patients for whom data were available. Abnormal neurologic signs were found or
      noted in medical records in 15 (42%) prospectively evaluated patients and 9 (64%)
      of 14 retrospectively evaluated patients for whom data were available. No patient
      had evidence of congenital or non-neurologic sequelae such as cutaneous or
      cardiovascular manifestations of syphilis. No patient had a positive
      cerebrospinal fluid VDRL test, 1 had more than 5 x 10(6) leukocytes per liter (5
      leukocytes per mm3), and 6 (9%) had elevated total protein levels in the
      cerebrospinal fluid. Previous therapy for syphilis was not associated with lower
      serum VDRL reactions, neurologic symptoms and signs, or cerebrospinal fluid
      findings. In the absence of other indications, routine examination of the
      cerebrospinal fluid in seropositive Southeast Asian refugees who have nonspecific
      neurologic symptoms has a low yield, perhaps because of the high prevalence of
      yaws in this population, and may not be warranted.

PMID- 8993200
TI  - Hospital volume influences outcome in patients undergoing pancreatic resection
      for cancer.
AB  - Surgical resection is the only possibly curative treatment of malignant
      pancreatic neoplasms, but major pancreatic resection for cancer is associated
      with high rates of morbidity and mortality. The objective of this study was to
      determine the relation between hospital volume and outcome in patients undergoing
      pancreatic resection for malignancy in California. Data were obtained from
      reports submitted to the Office of Statewide Health Planning and Development by
      all California hospitals from 1990 through 1994. Patient abstracts were analyzed
      for each of 1,705 patients who underwent major pancreatic resection for
      malignancy. Of the 298 reporting hospitals, 88% treated fewer than 2 patients per
      year; these low-volume centers treated the majority of patients. High-volume
      providers had significantly decreased operative mortality, complication
      associated mortality, patient resource use, and total charges and were more
      likely than low-volume centers to discharge patients to home. These differences
      were not accounted for by patient mix. This study supports the concept of
      regionalizing high risk procedures in general surgery, such as major pancreatic
      resection for cancer.

PMID- 8993202
TI  - Radiodosimetry in nuclear medicine.

PMID- 8993201
TI  - Radiation synovectomy.

PMID- 8993203
TI  - Scintimammography--a new tool for breast cancer diagnosis.

PMID- 8993205
TI  - Role of lung scanning in patients with pulmonary embolism.

PMID- 8993206
TI  - Use of bone mineral measurements in the management of osteoporosis.

PMID- 8993204
TI  - Cholescintigraphy in acute and chronic gallbladder dysfunction.

PMID- 8993207
TI  - Collimation approaches to 511-keV imaging.

PMID- 8993208
TI  - Detection and localization of gastrointestinal bleeding.

PMID- 8993209
TI  - Acute renal failure complicating nonfulminant hepatitis A.

PMID- 8993210
TI  - Intussusception in an adult.

PMID- 8993211
TI  - Current pharmacologic treatment of multiple sclerosis symptoms.
AB  - About 350,000 persons in the United States have multiple sclerosis, and primary
      care physicians are often called on to provide symptomatic therapy for these
      patients. We review our current pharmacologic approach to the management of
      multiple sclerosis exacerbations and the symptoms of spasticity, fatigue, bladder
      and bowel involvement, neurobehavioral complaints, pain syndromes, dystonic
      spasms, and tremor and ataxia.

PMID- 8993212
TI  - A primer for clinicians on mushroom poisoning in the West.

PMID- 8993213
TI  - Advances in the treatment of multiple sclerosis.

PMID- 8993214
TI  - Itraconazole-related amaurosis and vomiting due to digoxin toxicity.

PMID- 8993215
TI  - Isoniazid-related fatal hepatitis.

PMID- 8993216
TI  - The real vital signs.

PMID- 8993217
TI  - Emotional distress, physical symptoms and sleep disorders.

PMID- 8993218
TI  - Physicians and stress: shatter the cycle.

PMID- 8993219
TI  - Stress and domestic abuse.

PMID- 8993220
TI  - Panic attacks keep patients stressed.

PMID- 8993221
TI  - Patients with somatic preoccupation in primary care.

PMID- 8993222
TI  - Treatment of brain tumors: making progress?

PMID- 8993223
TI  - Treatment of tumors of the brain.

PMID- 8993224
TI  - Surgical management of colorectal metastases to the liver: role of resection and
      cryosurgery.
AB  - Long-term results of 41 patients who underwent hepatic resection and early
      experience with 21 patients treated by hepatic cryosurgery alone or combined with
      resection for colorectal metastases are presented. Patients treated by resection
      had three or fewer metastases, no perioperative mortality, and a mean follow-up
      of 43.5 months. The five-year overall survival is 34% with a median survival of
      48 months. By multivariate analysis, only transfusions correlated significantly
      with survival, but in a negative manner (p = 0.05). A mean of 4.3 units were
      transfused per patient, though only 25 patients actually received transfusions.

PMID- 8993225
TI  - Malignant rhabdoid tumor of the central nervous system.

PMID- 8993227
TI  - Recent advances in internal medicine.

PMID- 8993226
TI  - Coronary artery stenting during acute myocardial infarction in patients treated
      with IIb/IIIa anti-platelet antibodies: early outcome results.
AB  - Percutaneous transluminal coronary angioplasty has been shown to be an effective
      treatment for acute myocardial infarction. Despite encouraging results, this form
      of treatment is limited by a high incidence of recurrent ischemia either due to
      early rethrombosis or to restenosis of the infarct vessel within the first six
      months. Coronary artery stents decrease restenosis but are considered
      contraindicated in situations were thrombus is present. c7E3 is a potent anti
      platelet agent which inhibits thrombus formation. We developed 44 stents as part
      of angioplasty for acute myocardial infarction in 18 patients given c7E3. All
      patients obtained normal flow angiographically and no stent thrombosis was
      observed.

PMID- 8993228
TI  - Avoid patient abandonment--how to properly end a relationship with your patient.

PMID- 8993229
TI  - [Physico-chemical characterization and application for drug carrier of soybean
      derived sterols and their glucosides-containing liposomes].
AB  - With a rapid demand to decrease the side effect of drug, a variety of drug
      delivery systems have been developed. This review will focus on the development
      of liposomes with soybean-derived sterols and their glucosides for drug carriers.
      Current status and further perspectives in this research field are reviewed
      mainly based on the results obtained in our laboratory. First we studied the
      different physicochemical properties of dipalmitoylphos-phatidylcholine (DPPC)
      liposomes with soybean-derived sterols (SS) and their glucosides (SG). SS
      rigidifies the liposomal membrane but SG fluidizes it. SS stabilizes liposomes
      more than cholesterol that is conventionally used as stabilizing agents in
      liposomes. On the basis of this information, we developed liposomes with SS and
      SG for a drug carrier. Secondly we studied the stability of liposomes in the
      blood and biodistribution and found that liposomes with SS were stable as
      expected in vitro results. In particular, DPPC: SS (7:4, molar ratio) size 0.2
      micron showed long circulation. Thirdly successful targeting of the drugs to the
      liver was achieved by liposomes with SG. Finally, we succeeded in developing
      liposomal erythropoietin and doxorubicin using liposomes with SS for sustained
      release of drugs. Liposomal drugs increased the pharmacological effect compared
      with free drugs, suggesting a decrease of side effect and long circulation. The
      attempt for oral administration using liposomes of peptide drugs was carried out
      successfully. We have established that the study of physicochemical properties of
      liposomes is needed rationally as the distribution of drugs in liposomes and the
      rigidity of liposomal membrane, prior to the development of the drug carrier of
      liposomes. SS is useful to stabilize liposomes and SG to targeting to the liver
      parenchymal cells. This information can be useful and practical for the
      development of liposomes for drug carriers.

PMID- 8993230
TI  - [Chemical study of Indonesian medicinal plants].
AB  - A series of scientific expeditions in Indonesia for collecting informations and
      materials concerning locally used medicinal plants and Javanese traditional
      medicine "jamu" have been carried out by us since 1985. This article reviews
      pharmacochemical investigations of nine Indonesian medicinal plants: i.e.
      Pongamia pinnata (Papilionaceae), Fagara rhetza (Rutaceae), Calotropis gigantea
      (Asclepiadaceae), Beilschmiedia madang (Lauraceae), Caesalpinia major (Fabaceae),
      Peronema canescens (Verbenaceae), Taxus sumatrana (Taxaceae), Alyxia reinwardtii
      (Apocynaceae), and Merremia mammosa (Convolvulaceae), which were selected among
      plant materials collected in those surveys.

PMID- 8993231
TI  - [Retinoid antagonists].
AB  - Retinoids, retinoic acid and its bioisosters, regulate many biological functions
      such as cell differentiation, proliferation and embryonic development in
      vertebrates, through binding to and activating their specific nuclear receptors.
      There are two classes of nuclear receptors for retinoids, retinoic acid receptors
      (RAR alpha, beta, gamma) and retinoid X receptors (RXR alpha, beta, gamma).
      Several retinoid antagonists, which bind to but not activate RARs, have been
      reported. Among them, 4-(5H-7,8,9,10-tetrahydro-5,7,7,10,10
      pentamethylbenzo[e]naphtho [2,3-b][1,4]diazepin-13-yl)benzoic acid (LE135, 20) is
      a RAR beta-selective retinoid antagonist. Structure-activity relationships of
      LE135 (20) showed that the naphthalenyl analogs [LE540 (21) and LE550 (22)] are
      more potent retinoid antagonists in HL-60 assay. Contrary to the antagonistic
      activity of LE135 (20), an isomer of LE135 (20), 4-[5H-2,3-(2,5-dimethyl-2,5
      hexano)-5-methyldibenzo- [b,e][1,4]diazepin-11-yl)benzoic acid (HX600, 39)
      enhanced the activities of retinoids. Although the synergistic activity of HX600
      (39) can be explained by the binding to RXRs and the further activation of
      RAR/RXR heterodimer activated by retinoid (RAR ligand), the significantly
      different biological character of HX600 (39) from the typical RXR-selective
      ligand suggested the possibility of the participation of other nuclear receptors
      or cofactors in the retinoid synergism.

PMID- 8993232
TI  - [Specific inhibitory effect of hybrid liposomes on the growth of hybridoma cells
      in vitro].
AB  - Remarkably high inhibitory effects of the hybrid liposomes composed of L-alpha
      dimyristoyl-phosphatidylcholine (DMPC) and polyoxyethylenealkyl ether (C14(EO)n,
      n = 6-8 and C12(EO)n, n = 8-12)) on the growth of human lymphoma-human B
      lymphocyte hybridoma (HF) cells in vitro were obtained. The hybrid liposomes
      composed of 90 mol% DMPC/10 mol% C14(EO)n (n = 6-8) or C12(EO)n (n = 8-12) were
      more fluid as compared with 90 mol% DMPC/10 mol% C14(EO)4 or C12(EO)n (n = 4, 23)
      hybrid liposomes on the basis of fluorescence polarization measurements. These
      results suggest that the inhibitory effects of the hybrid liposomes on the growth
      of HF cells should be related to the membrane fluidity. No toxicity to normal
      rats in vivo was observed in the experiment using 90 mol% DMPC/10 mol% C14(EO)7
      or 90 mol% DMPC/10 mol% C12(EO)12 hybrid liposomes.

PMID- 8993233
TI  - [Heparin affinity high-performance liquid chromatography as an alternative to
      bioassay of CS23 mutein of recombinant human basic fibroblast growth factor].
AB  - We investigated whether a chemical assay by high-performance liquid
      chromatography (HPLC) as an alternative to the complicated and time-consuming
      bioassay for CS23 mutein of recombinant human basic fibroblast growth factor
      (rhbFGF-CS23) using the fetal bovine heart endothelial cell line ATCC CRL 1395.
      Physically, chemically or enzymatically denatured rhbFGF-CS23 was subjected to
      heparin affinity (HA)-HPLC and the bioassay. Good agreement was observed between
      the results obtained by these two methods. Moreover, HA-HPLC gave much more
      reproducible results (RSD = 1.9%, n = 6) than the bioassay (RSD = 7.4%, n = 18).
      HA-HPLC is therefore a simple, accurate and reproducible alternative to the
      bioassay for quality control and stability studies for rhbFGF-CS23 preparations.
      HA-HPLC is also considered to be applicable to assays for FGFs which have heparin
      affinity and biological activity similar to those of the CS23 mutein.

PMID- 8993234
TI  - Central nervous system injury after aortic operations: profits of amending old
      ways.

PMID- 8993235
TI  - Herbert Sloan Lecture. Extended operations for the treatment of lung cancer.

PMID- 8993236
TI  - Coronary microvascular reactivity after ischemic cold storage and reperfusion.
AB  - BACKGROUND: The coronary microvascular system is important in the regulation of
      myocardial perfusion. Preservation of microvascular reactivity may be important
      in those hearts undergoing ischemic storage for transplantation. Endothelium
      dependent relaxation of right and left ventricular coronary microvessels was
      examined in a canine model of heart transplantation. METHODS: Canine hearts
      underwent topical cooling, antegrade arrest, and 3 hours' ischemic cold storage
      at 4 degrees C using crystalloid cardioplegia (n = 8), Roe's solution (n = 8),
      and University of Wisconsin solution (n = 8). All groups underwent 1 hour of
      reperfusion in an isolated heart circuit. Noninstrumented canines were used as
      controls (n = 10). Coronary microvessels (100 to 200 microns in diameter) were
      examined in a pressurized, no-flow state with video microscopic imaging and
      electronic dimension analysis. RESULTS: Endothelium-dependent microvascular
      relaxation was examined in response to the receptor-dependent acetylcholine and
      to the receptor-independent calcium ionophore. Microvascular relaxation to
      acetylcholine in Roe's solution and University of Wisconsin solution was
      preserved (p = not significant) in the left ventricle, whereas crystalloid
      cardioplegia failed to preserve (p < 0.05) microvascular relaxation when compared
      with the control groups. Right ventricular microvascular relaxation was always (p
      < 0.05) less than left ventricular microvascular relaxation. Endothelium
      independent microvascular relaxation to nitroprusside was similar to that in
      controls, indicating normal smooth muscle responsiveness. CONCLUSIONS: Ischemic
      cold storage with Roe's solution and University of Wisconsin solution preserved
      microvascular relaxation in the left ventricle, whereas crystalloid cardioplegia
      failed to preserve microvascular relaxation. Right ventricular microvascular
      relaxation was impaired in all groups, but University of Wisconsin solution was
      superior to crystalloid cardioplegia and Roe's solution. This suggests that
      microvascular dysfunction may be partially responsible for right ventricular
      dysfunction after heart transplantation. The choice of preservation solution may
      be important in preservation of the microvascular endothelium.

PMID- 8993237
TI  - Paraplegia after thoracoabdominal aortic aneurysm repair: is dissection a risk
      factor?
AB  - BACKGROUND: The association between aortic dissection and paraplegia or
      paraparesis (P/P) after thoracoabdominal aortic aneurysm repair is not clear.
      METHODS: Six hundred sixty patients underwent thoracoabdominal aortic aneurysm
      repair from 1986 through 1995 using selective atriodistal bypass, liberal
      reattachment of critical intercostal arteries, moderate heparinization, and
      permissive mild hypothermia. Dissection was present in 163 patients (24.7%) and
      absent in 497 (75.3%). RESULTS: Early mortality occurred in 7.4% overall, and did
      not differ between patients with nondissection, acute dissection, or chronic
      dissection. The incidence of P/P was 5.4% overall, 5.5% without dissection, and
      5.0% with dissection. The risk of P/P for acute versus chronic dissection was 19%
      versus 2.9%, respectively (p = 0.011). Rupture and Crawford extent II were
      predictive of the development of P/P. In patients at high risk for P/P (ie,
      Crawford extent I or II), atriodistal bypass reduced the intercostal artery
      ischemic time, and reattachment of critical intercostal arteries (T8 to L1)
      reduced the incidence of P/P. CONCLUSIONS: Acute dissection increases the risk of
      P/P after thoracoabdominal aortic aneurysm repair; using contemporary methods,
      however, chronic dissection does not increase the risk of postoperative P/P.
      Critical intercostal artery reattachment and atriodistal bypass are beneficial in
      patients undergoing extensive repairs.

PMID- 8993238
TI  - Effects of surgical manipulation on coronary stents: should surgical strategy be
      altered?
AB  - BACKGROUND: Coronary artery bypass grafting is usually indicated for those
      patients who undergo open heart surgical procedures who have previously undergone
      percutaneous transluminal coronary angioplasty regardless of the absence of
      stenosis. Occasionally, however, if the treated artery has remained patent for
      many years and there is a shortage of conduit material or the patient is
      undergoing a complex operation, the branch is left ungrafted. With the gaining
      popularity of coronary stent placement, patients with these devices are
      undergoing open heart operations with increasing frequency. METHODS: To determine
      whether normal surgical manipulation during open heart surgical procedures
      results in obliteration of the Palmaz-Schatz stents previously deployed in the
      epicardial arteries, we developed an experimental model using ten isolated adult
      pig hearts. This allowed us to perform stent deployment and surgical manipulation
      and to apply direct pressure on the stented areas, with each heart evaluated by
      angioscopy and angiography and, finally, stent explantation. RESULTS: Retraction
      of the heart resulted in severe deformity of all left anterior descending artery
      stents, mild deformity of those in the circumflex artery, and mild or no
      deformity of those in the right coronary artery. However, direct pressure over
      the stented epicardial arteries (enough to retract the heart) resulted in
      complete obliteration of every intracoronary stent. CONCLUSIONS: The findings
      from this study indicate that once the need for surgical revascularization
      arises, a previously stented coronary artery should be bypassed even if the
      angiographic findings are normal, because of the likelihood that manipulation
      during an open heart operation will result in significant deformity or
      obliteration of the stent.

PMID- 8993239
TI  - Effects of blood and crystalloid cardioplegia on adrenergic and myogenic vascular
      mechanisms.
AB  - BACKGROUND: This study compares the effects of cold blood and crystalloid
      cardioplegia on adrenergic and myogenic regulation of the coronary circulation.
      METHODS: Pigs were placed on cardiopulmonary bypass and hearts were arrested with
      a hyperkalemic crystalloid cardioplegic solution (Cryst CP) or blood cardioplegic
      solution (Blood CP) for 1 hour. Hearts of selected pigs were then reperfused for
      1 hour (Rep) and separated from cardiopulmonary bypass. Left ventricular
      perfusion and contractility and beta- and alpha 2-adrenergic and myogenic
      responses of the coronary circulation were examined. RESULTS: Relaxation of
      isolated, precontracted microvessels to isoproterenol (beta-adrenoceptor agonist)
      was reduced to a lesser extent after Blood CP as compared with Cryst CP.
      Relaxation to forskolin (adenylate cyclase activator) was reduced after Cryst CP,
      but was preserved after Blood CP. After 1 hour of postcardioplegia reperfusion,
      the respective responses to isoproterenol and forskolin were similar in vessels
      from the Cryst CP-Rep and Blood CP-Rep groups. The alpha 2-adrenoceptor-mediated,
      endothelium-dependent vascular relaxation to clonidine was decreased more after
      Cryst CP than after Blood CP. The relaxation to nitroprusside was not affected by
      either Cryst CP or Blood CP. Myogenic tone was decreased to a lesser extent after
      Blood CP versus Cryst CP. Baseline coronary blood flow, isoproterenol-induced
      increases of coronary blood flow, and indices of myocardial contractility were
      similar in the Blood CP-Rep and Cryst CP-Rep groups, both 5 and 60 minutes after
      initiation of reperfusion. CONCLUSIONS: Although Blood CP was superior to Cryst
      CP in preserving beta- and alpha 2-adrenoceptor function and myogenic tone in
      vitro, there was no demonstrable benefit of blood cardioplegia in the
      preservation of myocardial contractility or perfusion in this model of
      cardioplegia.

PMID- 8993240
TI  - Heparin coating with aprotinin reduces blood activation during coronary artery
      operations.
AB  - BACKGROUND: This study was performed to evaluate whether the combination of
      heparin-coated extracorporeal circuits (ECC) and aprotinin treatment reduce blood
      activation during coronary artery operations. METHODS: Sixty patients were
      prospectively divided into two groups (heparin-coated ECC and uncoated ECC
      groups), which were comparable in terms of age, sex, left ventricular function,
      preoperative aspirin use and consequent intraoperative aprotinin use, number of
      grafts, duration of aortic cross-clamping, and duration of cardiopulmonary
      bypass. Blood activation was assessed at different times during cardiopulmonary
      bypass by determination of complement activation (C3 and C4 activation products
      C3b/c and C4b/c and terminal complement complex), leukocyte activation
      (elastase), coagulation (scission peptide fibrinopeptide 1 + 2), and fibrinolysis
      (D-dimers). RESULTS: Univariate analysis showed that heparin-coated ECC, under
      conditions of standard heparinization, did not reduce perioperative blood loss
      and need for transfusion. Heparin coating, however, reduced maximum values of
      C3b/c (446 +/- 212 nmol/L versus 632 +/- 264 nmol/L with uncoated ECC; p =
      0.0037) and maximum C4b/c values (92 +/- 48 nmol/L versus 172 +/- 148 nmol/L with
      uncoated ECC; p = 0.0069). Levels of terminal complement complex, elastase,
      fibrinopeptide 1 + 2, and D-dimers were not significantly modified by the use of
      heparin-coated ECC. Multivariate analysis showed that the intergroup differences
      in maximum C3b/c and C4b/c values were more pronounced in women in part with high
      baseline values of C3b/c. We also found that aprotinin contributed to the
      reduction of maximum values of fibrinopeptide 1 + 2 and D-dimers, whereas heparin
      coating had no significant influence on these parameters. CONCLUSIONS: We found
      no evidence of combined properties of heparin-coated ECC and aprotinin in
      reducing complement activation, coagulation, and fibrinolysis. We therefore
      recommend use of both together to achieve maximal reduction of blood activation
      during cardiopulmonary bypass for coronary artery operations.

PMID- 8993241
TI  - Preoperative platelet dysfunction increases the benefit of aprotinin in
      cardiopulmonary bypass.
AB  - BACKGROUND: This study was designed to determine the benefit of aprotinin therapy
      in reducing bleeding during and after cardiopulmonary bypass in patients with
      preoperative platelet dysfunction. Platelet function involvement in the mechanism
      by which aprotinin acts was also investigated. METHODS: In a double-blind,
      randomized study, patients received high-dose aprotinin (n = 54) or placebo (n =
      52). Whole blood aggregation was measured preoperatively. Platelet function and
      activation in both groups were assessed intraoperatively and postoperatively at
      five times. RESULTS: Aprotinin significantly reduced perioperative bleeding and
      postoperative blood transfusion. Placebo-treated patients with reduced
      preoperative platelet aggregation bled more postoperatively, but aprotinin
      reduced the bleeding in patients with normal or reduced platelet function to
      similar levels. Any cardiopulmonary bypass-induced changes in platelet
      aggregation, platelet activation as measured by P-selectin expression, and von
      Willebrand factor antigen and function were similar in aprotinin-treated and
      placebo-treated groups. CONCLUSIONS: The mechanism by which aprotinin reduced
      bleeding was independent of any effect on platelet function. However, aprotinin
      produced a greater reduction in bleeding among patients whose condition was
      hemostatically compromised by preoperative platelet dysfunction.

PMID- 8993242
TI  - Effect of aprotinin on plasma fibronectin levels during cardiopulmonary bypass.
AB  - BACKGROUND: Acute depletion of plasma fibronectin levels has been reported during
      and after cardiopulmonary bypass; degradation of fibronectin by proteolytic
      enzymes has been suggested as one of the causes. This study was designed to
      assess the possible preservation of fibronectin levels by aprotinin during
      cardiopulmonary bypass. METHODS: Plasma fibronectin levels were evaluated in 19
      patients undergoing either elective coronary artery bypass grafting or a valvular
      heart operation. The study was conducted prospectively in a controlled,
      randomized, double-blinded manner. Nine test patients (group A) received
      intraoperative, intravenous administration of aprotinin; 10 control patients
      (group B) received equivalent volume of normal saline solution. Fibronectin
      levels were measured immediately after induction of anesthesia (as the baseline
      for the study) and at the following times: after 5 minutes on bypass, after 30
      minutes on bypass, immediately before the start of rewarming, and after being off
      bypass for 5 minutes, but before protamine administration. RESULTS: Both groups'
      basic characteristics were very similar. Group A patients were found to have
      significantly greater fibronectin levels than group B during and immediately
      after cardiopulmonary bypass (p < 0.002). CONCLUSIONS: Administration of
      aprotinin intraoperatively appears to result in better preservation of
      fibronectin levels during cardiopulmonary bypass. Although the mechanism of
      action of aprotinin as a proteolytic inhibitor remains unclear, it has been
      suggested that it exerts an inhibiting effect on proteolytic enzymes by forming
      an aprotinin-proteinase complex. The clinical implications of the greater level
      of fibronectin achieved by the intraoperative use of aprotinin during
      cardiopulmonary bypass need further evaluation.

PMID- 8993243
TI  - "Low-dose" aprotinin modifies hemostasis but not proinflammatory cytokine
      release.
AB  - BACKGROUND: Cytokines are implicated in the pathogenesis of the "whole-body
      inflammatory response" that may complicate the period after cardiopulmonary
      bypass (CPB). Low-Dose aprotinin in the pump during CPB has been shown to improve
      postoperative hemostasis and platelet preservation. We tested the hypothesis that
      low-dose aprotinin influences the inflammatory reaction (in terms of cytokine
      release) after CPB. METHODS: In a prospective, randomized study, 36 patients
      undergoing elective coronary artery bypass grafting were investigated. Nineteen
      patients received low-dose aprotinin (2 x 10(6) KIU (280 mg] in the pump), and a
      control group of 19 did not. Complement activation, cytokine production,
      leukocyte elastase release. D-dimer level, full blood count, postoperative blood
      loss, and transfusion requirements were analyzed before, during, and after after
      CPB. RESULTS: Interleukin-1 beta was not detected in either group, whereas traces
      of tumor necrosis factor-alpha were infrequently observed. Plasma elastase,
      interleukin-6, interleukin-8, and neutrophil count increased (p < 0.001) during
      and after CPB compared with the baseline levels, reaching a peak at 2 hours after
      protamine administration in both groups before returning toward baseline at 24
      hours. Proinflammatory cytokine markers did not differ significantly (p > 0.1)
      between the groups throughout the study period. The C5b-9 level increased (p <
      0.001) in both groups perioperatively, reaching its peak 15 minutes after
      protamine. Twenty-four-hour postoperative blood loss was significantly (p <
      0.001) reduced in the aprotinin group in association with markedly reduced D
      dimer levels (p < 0.001). Patients in the aprotinin group also received
      significantly less banked blood postoperatively than the control group (p <
      0.01). CONCLUSIONS: Low-dose aprotinin fails to modify proinflammatory cytokine
      release, yet confers hemostatic improvement through reduced fibrinolysis in
      patients undergoing routine coronary artery bypass grafting.

PMID- 8993245
TI  - Intraoperative hetastarch infusion impairs hemostasis after cardiac operations.
AB  - BACKGROUND: An outbreak of excessive bleeding after cardiac operations occurred
      at our institution when 5% albumin was in short supply and hetastarch became the
      preferred intraoperative colloid. As hetastarch may impair coagulation, we
      investigated the effects of its intraoperative administration on post-cardiac
      surgical hemostasis. METHODS: Indices of postoperative hemostasis were analyzed
      in 189 consecutive patients undergoing coronary artery bypass grafting. Three
      groups were compared: one group (n = 68) received a mean of 796 mL of hetastarch
      only in the operating room (a few minutes after cessation of cardiopulmonary
      bypass), another group (n = 59) received a mean of 856 mL postoperatively only,
      and a third group (n = 62) received no hetastarch. RESULTS: Compared with the
      other two groups, those patients administered hetastarch intraoperatively
      exhibited significant reductions in hematocrit and platelet count, a significant
      prolongation in the prothrombin time, and significant increases in both blood
      loss and hemostatic drug requirement. Also identified were obvious trends toward
      a greater transfusion requirement and reexploration rate for bleeding in the
      latter group. CONCLUSIONS: Hetastarch infusion just after weaning from
      cardiopulmonary bypass produces a clinically important impairment in post-cardiac
      surgical hemostasis. Intraoperative use of this agent during heart operations
      should be avoided until the safe timing of its administration is clarified.

PMID- 8993244
TI  - Differing effects of aprotinin and epsilon-aminocaproic acid on cytokine-induced
      inducible nitric oxide synthase expression.
AB  - BACKGROUND: Cell expression of inducible nitric oxide synthase (iNOS) is
      increased by cytokines, resulting in high endogenous levels of nitric oxide.
      Expression of iNOS has been implicated in organ injury, including myocardial
      reperfusion injury. Serine protease inhibitors reduce cytokine-induced iNOS
      expression. The protease inhibitors aprotinin and epsilon-aminocaproic acid
      (EACA), used to reduce blood loss after cardiac operations, were evaluated in
      vitro on cytokine-induced iNOS expression and nitric oxide production. METHODS: A
      murine bronchial epithelial cell line was stimulated with a mixture of cytokines
      (tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma) with or
      without aprotinin or EACA. The resultant iNOS expression was measured by northern
      blot analysis, and nitric oxide production was assessed by cell supernatant
      nitrite levels. RESULTS: Nitrite concentrations in the supernatant were
      significantly increased after cytokine stimulation; they were not affected by any
      concentration of EACA but were significantly (p < 0.05) reduced by aprotinin.
      Aprotinin significantly (p < 0.05) reduced cytokine-induced iNOS expression,
      whereas EACA had no effect. CONCLUSIONS: Aprotinin, but not EACA, reduces
      cytokine-induced nitric oxide production by inhibition of iNOS expression.
      Because increased endogenous nitric oxide levels secondary to iNOS activation
      have been implicated in organ injury, aprotinin may have clinical benefit
      compared with EACA when used for cardiac operations.

PMID- 8993247
TI  - Aortic arch operation using selective cerebral perfusion for nondissecting
      thoracic aneurysm.
AB  - BACKGROUND: Risks of increasing mortality and disability in aortic arch
      operations using the selective cerebral perfusion method for nondissecting
      aneurysm have not yet been determined. A multicenter, retrospective study was
      employed. METHODS: The subjects were 143 patients who were admitted to one of the
      nine cardiovascular centers between January 1988 and December 1993, including 15
      with ruptured aneurysm. A graft replacement of the transverse aortic arch or
      distal arch was performed in 80 patients, extensive aortic reconstruction
      comprising simultaneous replacement of the ascending or descending thoracic aorta
      (or both) in 46, and patch repair of involved arch in 17. The mean postoperative
      follow-up period was 19 months. RESULTS: Hospital mortality was 36/143 patients
      (25.2%). Univariate analysis revealed that age of 70 years or more, ruptured
      aneurysm, and renal dysfunction affected hospital mortality. Neurologic deficits
      were noted in 15 patients (10.5%). Reoperation was performed in 13 patients for
      residual distal aneurysm or false aneurysm. Late death occurred in 10 patients
      and were due to vascular complications in 6. Multivariate analysis confirmed that
      aneurysmal rupture and renal dysfunction were independent predictors for vascular
      death including hospital mortality. CONCLUSIONS: The present study confirmed that
      age, aneurysmal rupture, and renal dysfunction were significant predictors for
      mortality and disability in the aortic arch operation using selective cerebral
      perfusion for nondissecting thoracic aneurysm.

PMID- 8993246
TI  - Hyperkalemia exposure impairs EDHF-mediated endothelial function in the human
      coronary artery.
AB  - BACKGROUND: My colleagues and I have found in the porcine coronary artery that
      the pathway other than the nitric oxide (NG-nitro-L-arginine [L-NNA]-sensitive)
      and cyclooxygenase (indomethacin-sensitive) pathways of endothelium-dependent
      relaxation, related to the endothelium-derived hyperpolarizing factor (K+ channel
      related), are altered after exposure to hyperkalemia. The present study was
      designed to examine whether this effect exists in the human coronary artery.
      METHODS: Coronary artery rings obtained from explanted fresh human hearts were
      studied in organ chambers under physiologic pressure. The endothelium-dependent
      relaxation in response to calcium ionophore A23187 was studied in U46619 (30
      nmol/L)-induced precontraction in the presence of the cyclooxygenase inhibitor
      indomethacin (7 mumol/L) and the nitric oxide biosynthesis inhibitor L-NNA (300
      mumol/L). The effect of incubation with 20 mmol/L K+ for 1 hour on the relaxation
      was examined in other coronary rings. RESULTS: In control rings, A23187 induced a
      maximal relaxation of 50.7% +/- 3.2% (n = 6). After 1 hour of exposure to 20
      mmol/L K+, the relaxation was reduced to 30.4% +/- 4.6% (n = 6; p = 0.005).
      Incubation with hyperkalemia also significantly reduced the sensitivity
      (increased effective concentration that caused 50% of maximal relaxation) of the
      indomethacin- and L-NNA-resistant relaxation (-7.37 +/- 0.17 versus -8.28 +/-
      0.27 log mol/L; p = 0.019). CONCLUSIONS: Exposure to hyperkalemia reduces the
      indomethacin- and L-NNA-resistant, endothelium-dependent (endothelium-derived
      hyperpolarizing factor-related) relaxation in the human coronary artery. This
      suggests that the previously proposed mechanism of coronary dysfunction after
      exposure to cardioplegic and organ preservation solutions in animal vessels is
      also valid in the human heart.

PMID- 8993248
TI  - Operation for nondissecting aneurysm in the descending thoracic aorta.
AB  - BACKGROUND: Little is known about the risks of mortality and morbidity after
      descending thoracic aortic aneurysm repair using left heart bypass and temporary
      arterioarterial bypass. METHODS: A multicenter, retrospective study was performed
      on 120 patients who were admitted to one of nine cardiovascular centers between
      January 1988 and December 1993 and underwent operation for nondissecting thoracic
      aortic aneurysm. The present series included 10 patients with ruptured aneurysm.
      Graft replacement was performed in 95 patients, patch repair in 22, and suture of
      the ruptured aorta in 3. Venoarterial bypass was used in 45 patients, left heart
      bypass in 56, and temporary arterioarterial bypass in 19 as circulatory support.
      The mean postoperative follow-up period was 30 +/- 21 months. RESULTS: Hospital
      mortality occurred in 7 patients (5.8%). Univariate analysis revealed that only
      aneurysmal rupture was related to hospital mortality. Brain or cord injury was
      observed in 4. Of nine deaths that occurred after discharge, five were related to
      aneurysm and two were due to vascular event. No significant difference was
      noticed in probability of survival according to the circulatory supporting
      method. Only aneurysmal rupture affected probability of survival. Multivariate
      analysis revealed that aneurysmal rupture was the only independent predictor for
      vascular death including hospital mortality. CONCLUSIONS: The present study
      confirms that aneurysmal rupture is a significant predictor for mortality and
      morbidity in aortic operations for nondissecting descending thoracic aneurysm,
      and that a similarly good outcome would be expected when using left heart bypass,
      temporary arterioarterial bypass, or venoarterial bypass.

PMID- 8993249
TI  - Is warm retrograde blood cardioplegia better than cold for myocardial protection?
AB  - BACKGROUND: This study tests the hypothesis that continuous normothermic
      retrograde blood cardioplegia is superior to cold intermittent blood cardioplegia
      in protecting the left and right side of the heart transmurally during an
      extended cross-clamping period. METHODS: Twelve anesthetized, open chest dogs
      were placed on cardiopulmonary bypass and randomized to receive continuous warm
      (n = 6) or intermittent cold cardioprotection (n = 6) during a 3-hour aortic
      cross-clamp period. Transmural left ventricular muscle biopsy specimens were
      taken before the initiation of cardiopulmonary bypass and 90 and 180 minutes
      after cross-clamping. Right ventricular (RV) biopsy specimens were taken 180
      minutes after aortic cross-clamping. Biopsy specimens were analyzed for adenosine
      triphosphate, creatine phosphate, and lactate levels and for morphologic changes
      via electron microscopy. RESULTS: At the end of 180 minutes of cardiopulmonary
      bypass, the adenosine triphosphate contents of endocardial and epicardial halves
      of the left ventricular myocardium were only slightly degraded in both
      cardioplegia groups; a significantly greater reduction in adenosine triphosphate
      levels occurred in the RV of the warm compared with the cold group (p < 0.02).
      The difference in creatine phosphate values in the left ventricle between the
      cold group (35.2 +/- 23.4 nmol/mg cardiac protein) and the warm animals (64.4 +/-
      24.9 nmol/mg cardiac protein) was not statistically significant, but the RV
      creatine phosphate stores were significantly better preserved in the warm
      compared with the cold cardioplegia group (p < 0.02). Lactate levels increased to
      a similar extent in both groups, but both values rose significantly over baseline
      (p < 0.03). Importantly the electron microscopic score of the left ventricle and
      RV indicated that cells were reversibly and not irreversibly damaged with both
      cardioplegic protections. CONCLUSIONS: These results suggest the following: (1)
      Chemical arrest is a major contributor of myocardial preservation during
      diastolic arrest as used in clinical cardiac surgery. (2) Both methods preserve
      the ultrastructure of the myocytes transmurally during 3 hours of aortic cross
      clamping. (3) Both techniques protect the RV and left ventricle; however, to
      provide optimal protection of the RV, alternated retrograde and antegrade
      perfusion might be beneficial over retrograde cardioplegia flow alone, in
      particular with warm cardioplegia.

PMID- 8993250
TI  - Attenuation of changes in leukocyte surface markers and complement activation
      with heparin-coated cardiopulmonary bypass.
AB  - BACKGROUND: The inflammatory response induced by cardiopulmonary bypass can
      result in severe organ dysfunction in some patients. This postperfusion response
      is caused mainly by contact between blood and the foreign surface of the
      cardiopulmonary bypass equipment and includes adhesion of leukocytes to vascular
      endothelium, which precedes a series of events that mediate inflammatory damage
      to tissues. METHODS: Low-risk patients accepted for coronary artery bypass
      grafting were randomized to operation with the cardiopulmonary bypass surface
      either completely heparin coated (Duraflo II) or uncoated. There were 12 patients
      in each group. Blood plasma sampled during cardiopulmonary bypass was analyzed
      for complement activation (C3bc and terminal SC5b-9 complement complex) and
      neutrophil activation (lactoferrin and myeloperoxidase). In addition,
      neutrophils, monocytes, and platelets were counted, and the expression of surface
      markers on the neutrophils and monocytes (complement receptor [CR] 1, CR3, CR4,
      and L-selectin) and on the platelets (P-selectin and CD41) was quantified with
      flow cytometry. RESULTS: Clinical and surgical results were similar in both
      groups. In the group with the heparin-coated surface, the formation of the
      terminal SC5b-9 complement complex was significantly reduced, and the counts of
      circulating leukocytes and platelets were significantly less reduced initially
      but were higher at the end of cardiopulmonary bypass compared with baseline.
      Also, the expression of CR1, CR3, and CR4 was significantly less upregulated and
      the L-selectin, significantly less downregulated on monocytes and neutrophils.
      CONCLUSIONS: We conclude that heparin coating reduces complement activation and
      attenuates the leukocyte integrin and selectin response that occurs when uncoated
      circuits are used.

PMID- 8993251
TI  - Ross-Konno operation with resection of endocardial fibroelastosis for critical
      aortic stenosis with borderline-sized left ventricle in neonates.
AB  - BACKGROUND: Critical aortic stenosis with severe concentric left ventricular
      hypertrophy and endocardial fibroelastosis has a substantial mortality rate when
      the conventional therapeutic strategy, ie, open surgical or balloon
      valvuloplasty, is applied. During the last decade, univentricular repair (Norwood
      operation) and heart transplantation have evolved as the only viable therapeutic
      options. An alternative in patients with borderline hypoplastic left heart
      syndrome consists of performance of a Ross-Konno operation with surgical
      enlargement of the left ventricular cavity, a procedure that has the advantage of
      achieving a two-ventricle repair. METHODS: Two neonates and 2 young infants with
      critical aortic stenosis, concentric left ventricular hypertrophy, and severe
      endocardial fibroelastosis, with echocardiographically documented antegrade flow
      in the ascending aorta, underwent a Ross-Konno operation combined with extensive
      endocardial and myocardial resection of the left ventricular septum and free
      wall. The incision in the ventricular septum was closed with a wide cuff of
      infundibular muscle that was harvested in continuity with the pulmonary
      autograft. RESULTS: In all 4 patients, the operation resulted in normal aortic
      valve function, marked reductions of width of the left ventricular septum
      (median, 6.5 mm, versus 11 mm preoperatively) and the left ventricular posterior
      free wall (median, 8.5 mm, versus 15.5 mm preoperatively), and enlargement of the
      left ventricular end-diastolic volume (median, 12.5 cm3, versus 6.5 cm3
      preoperatively). Three patients had an uneventful recovery, with gradual
      improvement of left ventricular diastolic and systolic function during the first
      postoperative week; 1 neonate with associated mitral regurgitation died of left
      ventricular failure. CONCLUSIONS: The Ross-Konno procedure with resection of
      endocardial fibroelastosis may be a valuable adjunct for achieving a two
      ventricle repair in borderline hypoplastic left heart syndrome. The operation
      results in enlargement of the left ventricular stroke volume and improvement of
      left ventricular diastolic function; in addition, resection of endocardial
      fibroelastosis relieves the mechanical impairment of myocardial function and
      therefore may promote the potential for left ventricular growth.

PMID- 8993252
TI  - Previous open heart operation: a contribution to impaired outcome after cardiac
      transplantation?
AB  - BACKGROUND: There is still debate about whether previous cardiac operations are a
      risk factor for patient outcome after cardiac transplantation. As waiting lists
      for cardiac transplantation increase, adverse outcome criteria should be
      identified. METHODS: To assess this problem, we retrospectively analyzed 53
      patients with previous cardiac operations before heart transplantation and
      compared them with 53 control patients matched for sex and age. Patient groups
      were analyzed regarding their preoperative, intraoperative, and postoperative
      variables and survival. RESULTS: Ischemic times were comparable in both groups,
      but the duration of the operation was significantly longer in the study group
      (206.5 +/- 62.5 minutes, versus 156.0 +/- 36.7 minutes in controls; p < 0.05). In
      addition, postoperative blood loss was greater for the patients with previous
      cardiac operations (1,360 +/- 260 mL, versus 730 +/- 310 mL for controls; p <
      0.01). Postoperatively, the rate of rejection episodes and the incidence of graft
      atherosclerosis were comparable within the first 2 years. However, survival was
      significantly reduced in the study group (60.1%) after 4 years (versus 83.1% for
      controls; p < 0.05). CONCLUSIONS: Heart transplantation in patients with previous
      cardiac operations will lead to an impaired overall outcome. In addition, these
      patients have more postoperative complications.

PMID- 8993253
TI  - Late outcome and quality of life after complicated heart operations.
AB  - BACKGROUND: Patients with severe postoperative complications consume a great deal
      of the economic resources for intensive care. Our knowledge of the late outcome
      and quality of life of these patients is scarce. METHODS: One thousand five
      hundred twenty-two patients undergoing cardiac operations during 1991 and 1992
      were studied, and the 100 patients who needed the most expensive treatment were
      identified. The patients were retrospectively risk scored (Higgins score), and
      the clinical outcome was studied. The surviving patients were followed up for 2
      years after the operation. Their quality of life and remaining symptoms were
      assessed. RESULTS: No significant age difference between groups was observed.
      There were significantly more women, emergency cases, high-risk patients, and
      postoperative complications in the studied group. Mortality rate during the first
      postoperative year was significantly higher in the studied group. Later the
      difference in mortality rate between the groups decreased. At the 2-year follow
      up all the 72 surviving patients in the study group had returned home with less
      physical and psychological symptoms related to their heart disease. CONCLUSIONS:
      The cost of treating severe complications in the intensive care unit is high.
      However, the results of the present study indicate that even a very complicated
      postoperative course is not incompatible with a successful outcome in the long
      run.

PMID- 8993255
TI  - Early repair of postinfarction ventricular septal rupture.
AB  - BACKGROUND: Postinfarction rupture of the interventricular septum is usually
      fatal without surgical intervention. The optimal timing and the most appropriate
      technique of surgical repair remain unsettled. METHODS: The results of surgical
      closure of postinfarction ventricular septal defect in a consecutive series of
      patients seen over a 24-year period were reviewed and analyzed. Late follow-up
      was obtained in all patients who survived the operation. RESULTS: Sixty of 76
      patients treated surgically exhibited cardiogenic shock, low cardiac output
      syndrome, or both at the time of operation. A plan of early operative
      intervention was followed in these unstable patients, with 60% of them undergoing
      repair within 24 hours of septal rupture. For the entire series of patients, the
      hospital mortality rate was 40.8%; survival was 41.5% at 5 years and 25.6% at 10
      years postoperatively. CONCLUSIONS: Significant trends observed during the period
      of study were a more aggressive stance regarding surgical intervention in all
      patients who presented with hemodynamic instability and improved survival in
      those patients who presented with septal rupture complicating an inferior
      myocardial infarction.

PMID- 8993254
TI  - Synergistic immunosuppression caused by high-dose methylprednisolone and
      cardiopulmonary bypass.
AB  - BACKGROUND: Steroid use during cardiac operations may reduce the risk of
      postperfusion lung syndrome, but both cardiopulmonary bypass and steroids are
      immunosuppressive. The synergistic effects of the bypass and steroids on
      patients' immunologic activities, hemodynamics, and metabolisms during and after
      heart operations have not been clarified systematically. METHODS: Twenty-four
      patients undergoing valve replacement were studied in a randomized, double-blind
      trial. Twelve of these patients (S group) received bolus methylprednisolone, 20
      mg/kg body weight, and the remaining 12 patients (C group) received a placebo
      intravenously before and after bypass. Blood cell count, C-reactive protein,
      lymphocyte surface markers (CD3, CD4, CD8, CD16, and CD20), phytohemagglutinin
      response, interleukin-2 production, and natural killer cell activity were
      examined on admission through day 7. Cardiac output, blood gas, electrolyte,
      lactate, and serum glucose levels were examined perioperatively. RESULTS: The
      peak white blood cell count in the S group was higher than that in the C group
      (analysis of variance: p [group] = 0.0436). The peak C-reactive protein level was
      higher in the C group than in the S group (p [group] < 0.0001). From the analysis
      of the surface markers, the steroid increased the natural killer cells before and
      soon after bypass (p [group] = 0.0117), and later tended to increase the CD4+ T
      and B cells during the postoperative recovery period. The phytohemagglutinin
      response in both groups decreased after bypass (p [time] < 0.0001), but the
      steroid caused exaggerated decreases before (p < 0.01 by Student's t test) and
      soon after (p < 0.001) bypass in the S group (analysis of variance: p [group] =
      0.0127). The interleukin-2 production was suppressed by bypass alone after the
      bypass in the C group, but was further suppressed by the steroid before and after
      bypass in the S group (p [group] = 0.0446). The cardiac index, water balance,
      electrolytes, arterial oxygen tension, and timing of extubation were not
      different between the groups. In contrast, the glucose (p [group] = 0.0486) and
      lactate (p [group] = 0.0525) levels were higher in the S group than those in the
      C group. CONCLUSIONS: T-cell functions are synergistically suppressed by
      cardiopulmonary bypass and high-dose methylprednisolone in heart operations. The
      hemodynamic benefits of the steroid are negligible, whereas glucose tolerance is
      worsened by the steroid during bypass.

PMID- 8993256
TI  - Open heart operations after renal transplantation.
AB  - BACKGROUND: Because of the increasing number of renal transplantations performed,
      secondary cardiac operations in these patients are discussed concerning their
      impact on patient and graft survival. METHODS: We reviewed our experience in 45
      patients (33 male and 12 female) who underwent open heart operations after
      previous renal transplantation. Thirty-one patients (group I) received coronary
      artery bypass grafting and 14 (group II) underwent valve replacement. Mean age at
      the time of operation was 55 +/- 9 years. The interval between renal
      transplantation and cardiac operation was 57 +/- 39 months (range, 5 days to 174
      months). All patients had functioning renal allografts with preoperative serum
      creatinine levels ranging from 100 to 338 mol/mL (mean +/- standard deviation,
      195 +/- 86). RESULTS: Overall early operative mortality (30 days) was 8.8% (group
      I, 1 patient; group II, 3 patients). Underlying causes of death were septic
      endocarditis (n = 2, group II), necrotizing enterocolitis (n = 1, group I), and
      myocardial infarction (n = 1, group II). One further patient in group II also
      died of septic endocarditis after 69 days (in-hospital death). The mean follow-up
      of the 40 surviving patients was 44 +/- 31 months. There was another late death
      (24 months postoperatively) caused by coagulopathy. Four patients had returned to
      hemodialysis at intervals of 27 to 83 months (mean, 51 months) because of renal
      transplant failure. In all patients, the function of the renal allograft was not
      impaired by open heart operation. CONCLUSIONS: Open heart operations in renal
      transplant recipients have acceptable mortality and morbidity rates. In almost
      all patients, function of the transplanted organ can be maintained at the
      preoperative level.

PMID- 8993257
TI  - Preconditioning and hypothermic cardioplegia protect human heart equally against
      ischemia.
AB  - BACKGROUND: The purpose of this study was to determine whether transient ischemic
      preconditioning protects human myocardium against normothermic ischemic injury.
      METHODS: Isolated human right atrial trabeculae were suspended in an organ bath
      with oxygenated Tyrode's solution at 37 degrees C and field stimulated at 1 Hz.
      Developed force was recorded. Trabeculae (Warm I/R) received normoxic perfusion
      before 45 minutes of normothermic simulated ischemia (hypoxic, substrate-free
      buffer with pacing at 3 Hz) and 120 minutes of reperfusion. Preconditioned
      trabeculae (Warm IPC) were subjected to 5 minutes of normothermic simulated
      ischemia and 10 minutes of perfusion before normothermic simulated ischemia
      reperfusion injury. Trabeculae (Cold I/R) were subjected to hypothermic (4
      degrees C) ischemia (hypoxic buffer) for 4 hours and 60 minutes of reperfusion
      (37 degrees C). Preconditioned trabeculae (Cold IPC) were pretreated with 5
      minutes of normothermic simulated ischemia before hypothermic ischemia and 60
      minutes of reperfusion. At the end of reperfusion, trabeculae were frozen at -70
      degrees C and assayed for tissue creatine kinase activity. RESULTS: At the end of
      reperfusion, warm preconditioned trabeculae (Warm IPC) recovered 51% +/- 5% of
      baseline developed force, whereas warm I/R trabeculae recovered 24% +/- 3% (p <
      0.05). Tissue creatine kinase levels reflecting preserved tissue viability were
      sustained in Warm IPC trabeculae (1,183 +/- 204 U/g), whereas nonpreconditioned
      control trabeculae (Warm I/R) exhibited lower levels of enzymatic activity (403
      +/- 32 U/g) (p < 0.05). In contrast, Cold IPC trabeculae recovered 47% +/- 5% and
      Cold I/R, 56% +/- 8% of baseline developed force at the end of reperfusion (p >
      0.05). CONCLUSIONS: We conclude that transient ischemic preconditioning protects
      human myocardium against normothermic ischemic injury.

PMID- 8993258
TI  - Adenosine prevents hyperkalemia-induced calcium loading in cardiac cells:
      relevance for cardioplegia.
AB  - BACKGROUND: Hyperkalemic cardioplegic solutions effectively arrest the heart but
      also induce membrane depolarization, which could lead to intracellular Ca2+
      loading and contribute to ventricular dysfunction associated with cardiac
      operations. Adenosine, which possesses cardioprotective properties, has been
      proposed as an adjunct to conventional cardioplegic solutions. However, it is not
      known whether adenosine supplementation enables cardiac cells to withstand
      hyperkalemia-induced Ca2+ loading. METHODS: Single ventricular cardiomyocytes
      were isolated from guinea pig hearts, loaded with a Ca(2+)-sensitive fluorescent
      probe, and imaged by digital epifluorescent microscopy. The emitted fluorescence
      of the probe, a measure of the intracellular Ca2+ concentration, was recorded
      from single myocytes during hyperkalemic challenges in the absence and the
      presence of adenosine to assess the protective effectiveness of this agent.
      RESULTS: Hyperkalemic solutions induced intracellular Ca2+ loading (estimated
      intracellular Ca2+ concentration, 88 +/- 5 nmol/L before and 1,825 +/- 112 nmol/L
      after addition of 16 mmol/L KCl). Adenosine (1 mmol/L) prevented K(+)-induced
      Ca2+ loading (intracellular Ca2+ concentration, 86 +/- 6 nmol/L before and 85 +/-
      8 nmol/L after exposure to K+). Whereas glyburide (3 mumol/L), an antagonist of
      adenosine triphosphate-sensitive K+ channels, had no effect, staurosporine (200
      nmol/L) and chelerythrine (5 mumol/L), two inhibitors of protein kinase C, did
      abolish the action of adenosine. CONCLUSIONS: Adenosine prevents hyperkalemia
      induced Ca2+ loading in cardiomyocytes. This effect is due to a direct action on
      ventricular cells, as the preparation employed was free from atrial, neuronal,
      and vascular elements, and appears to be mediated through a protein kinase C
      dependent mechanism. The property of adenosine to prevent hyperkalemia-induced
      Ca2+ loading may contribute to the cytoprotective efficacy of this agent as an
      adjunct to conventional hyperkalemic cardioplegic solutions.

PMID- 8993259
TI  - Flow characteristics of the Hemopump: an experimental in vitro study.
AB  - BACKGROUND: The Hemopump (DLP/Medtronic) has been in clinical use for about 7
      years. There is still no adequate way of determining actual output from the three
      available pump systems in the clinical situation. If the pump is completely
      stopped during weaning from the device, there is a possibility of back-leakage
      through the pump, endangering the patient from regurgitation into the left
      ventricle. It can also make it more difficult to judge the recovery of heart
      function because of a volume load of the left ventricle. The aim of this study
      was to evaluate in a standardized, experimental in vitro model the output from
      three different-sized Hemopump catheters at various pressure levels and to
      quantify the back-flow through the pumps. METHODS: The Hemopump models were
      tested in an in vitro study regarding total outflow at various speeds at three
      pressure levels. The back-flow through the pumps was also measured with the pumps
      at a complete stop. RESULTS: The outflow from the Hemopumps ranged from 0.4 to
      4.5 L/min, depending on which pump and speed were used. Variations in total
      output, depending on speed and various pressure settings, could be up to 0.4
      L/min. Back-flow through the pump into the left ventricle may be as great as 1.6
      L/min. CONCLUSIONS: The flow outputs from the different Hemopump models were
      reproducible over time and were closely related to the resistance of the model.
      The Hemopump, if not running, can induce substantial regurgitation through the
      pump into the left ventricle.

PMID- 8993260
TI  - Relative changes in cerebral blood flow during cardiac operations using xenon-133
      clearance versus transcranial Doppler sonography.
AB  - BACKGROUND: Changes in cerebral blood flow (CBF) during cardiac operations have
      implications in terms of postoperative neurologic and neuropsychological
      dysfunction. Current techniques of CBF measurement are cumbersome and invasive.
      Transcranial Doppler sonography offers a noninvasive means of assessing changes
      in CBF. The aim of this study was validation of this technique with existing
      methods of CBF measurement during cardiac operations. METHODS: We compared the
      changes in CBF using xenon-133 clearance with changes in middle cerebral artery
      velocity by transcranial Doppler sonography (VMCA) using pH-stat and alpha-stat
      acid-base management during cardiopulmonary bypass. Measurements were taken (1)
      before bypass, (2) at 28 degrees C on bypass, (3) at 37 degrees C on bypass, and
      (4) after bypass. Relative changes in CBF and VMCA, calculated as the percent
      change from the prebypass baseline value normalized to 100%, were used in this
      analysis. RESULTS: During the hypothermic phase of cardiopulmonary bypass, CBF
      and VMCA increased by 45.9% and 51.8%, respectively (p < 0.001), during pH-stat
      acid-base management but decreased by only 26.4% and 22.4%, respectively (p <
      0.0001), during alpha-stat acid-base management. Linear regression analysis of
      the absolute changes in CBF (mL . 100 g-1 . min-1) and VMCA (cm/s) showed a
      significant correlation (r = 0.60; r2 = 0.36; p < 0.0001), but a better
      correlation was obtained when relative changes in CBF and VMCA were compared (r =
      0.89; r2 = 0.79; p < 0.0001). CONCLUSIONS: Measurements of VMCA, expressed as
      relative changes of a pre-cardiopulmonary bypass level (using the noninvasive
      transcranial Doppler sonographic technique), can be used to examine CBF changes
      during cardiopulmonary bypass.

PMID- 8993261
TI  - Video-assisted thoracoscopic operation for interruption of patent ductus
      arteriosus in adults.
AB  - BACKGROUND: Patent ductus arteriosus (PDA) is a frequent congenital heart disease
      encountered in premature neonates, infants, and children. Video-assisted
      endoscopic techniques have been used in PDA interruption since 1993. Almost all
      the experiences are in pediatric patients. Applications in adults with PDA have
      been limited. METHODS: We report our experience of video-assisted thoracoscopic
      surgical ligation of PDA in adults. From August 1995 to January 1996, 60 patients
      with PDA were operated on with a video-assisted thoracoscopic technique. Twelve
      adults were identified with mean age of 30 years (range, 20 to 57 years). With
      the patient under general anesthesia and double-lumen endotracheal intubation,
      two 5-mm holes were made in the left lateral chest wall. Another 4-cm incision
      was made in the left third intercostal space for manipulation, dissection, and
      ligation. Conventional surgical instruments were used except an endoscopic
      grasper and an endoscopic tube that connected to a video camera. The surgical
      procedure was viewed on a video screen. Transesophageal echocardiography was used
      for monitoring during PDA ligation. RESULTS: All patients had successful ligation
      of the PDA. There was no surgical mortality, but there was one morbidity;
      transient recurrent nerve injury, which recovered 3 months later. Ten patients
      were extubated in operative room and 2 patients were extubated 2 hours after the
      operation. Tube thoracostomy was performed in the first 2 cases; it was omitted
      thereafter. No patients needed narcotic to control chest pain. Postoperative
      follow-up by echocardiography showed faint ductal flow in 1 patient without any
      murmur. All patients were discharged within 3 days after the operation.
      CONCLUSIONS: Our experience suggests that with refinement of instruments and
      surgical technique, video-assisted thoracoscopic surgical ligation can be safely
      applied not only in pediatric patients, but also in adults with PDA.

PMID- 8993262
TI  - Clinical-pathologic analysis of 40 patients with large cell neuroendocrine
      carcinoma of the lung.
AB  - BACKGROUND: The identification, classification, and appropriate treatment of
      patients with pulmonary carcinomas demonstrating neuroendocrine differentiation
      remains controversial. METHODS: Patients undergoing resection of lung cancer at
      Washington University since 1986 were reviewed to identify all large cell
      neuroendocrine carcinomas. Cases were segregated into large, small, or mixed cell
      categories, and graded as moderate ("atypical carcinoid") or poorly
      differentiated (all higher grade lesions). All patients' charts were reviewed and
      referring physicians contacted to ascertain cancer treatment after resection and
      follow-up status. RESULTS: Forty patients were identified with large cell
      neuroendocrine carcinoma: 8 moderate and 32 high-grade. Average follow-up was
      19.8 months. Stage distribution was as follows: I, 25; II, 6; III, 6; and VI, 3.
      Fifteen patients have no evidence of disease, 15 are dead of disease, and 6 are
      alive with disease. Five-year survival of the stage I patients is 18%; all-stage
      5-year survival is 13%. Of the 15 patients who died of their disease, 80% had
      stage I or II disease. Postoperative chemotherapy, radiation therapy, or both
      were given to 9 of 26 patient in stage I, with six deaths (67%). Six of 17
      patients (35%) with stage I disease died after no postoperative intervention.
      CONCLUSIONS: Large cell neuroendocrine carcinomas identified by histologic
      examination have a remarkably poor prognosis even in very early stage disease.
      Adjuvant therapy did not improve survival.

PMID- 8993263
TI  - Reduction pneumonoplasty for patients with a forced expiratory volume in 1 second
      of 500 milliliters or less.
AB  - BACKGROUND: Patients with severely impaired pulmonary function are considered at
      high risk for emphysema operations. We prospectively evaluated 44 patients with a
      forced expiratory volume in 1 second of 0.5 L or less undergoing reduction
      pneumonoplasty for dyspnea uncontrolled by medical management (confirmed by Borg
      and modified Medical Research Council dyspnea scales). METHODS: There were 28 men
      and 16 women (mean age, 66 years) with a mean preoperative forced expiratory
      volume in 1 second of 0.41 L (range, 0.23 L to 0.50 L). Preoperative therapy
      consisted of bronchodilators (100% of patients), oxygen (80%), and steroids
      (72%). Hypercarbia was seen in 80% of patients, and 66% had pulmonary
      hypertension. Unilateral reduction pneumonoplasty by a video-assisted thoracic
      surgical approach was performed in 34 patients, 6 patients underwent bilateral
      reduction pneumonoplasty by a video-assisted thoracic surgical approach, and 4
      patients underwent bilateral reduction pneumonoplasty by a video-assisted
      thoracic surgical approach, and 4 patients underwent bilateral reduction
      pneumonoplasty by median sternotomy. Discrete emphysematous regions were resected
      using staplers with buttressing, and regions of homogeneous emphysema were
      plicated with KTP or neodymium:yttrium-aluminum garnet laser radiation. RESULTS:
      There was one death within 30 days, two additional deaths within 60 days, and
      five additional deaths within 1 year. Hospital stay averaged 12 days. Intensive
      care unit stay averaged 4 days. Subjective improvement was noted by 89%. Borg and
      modified dyspnea scores improved from 7.6 to 4.5 (p < 0.01) and from 3.9 to 2.35
      (p < 0.01), respectively. Forced expiratory volume in 1 second was 0.62 L at 1
      year, a 51% improvement (p < 0.001). Forced vital capacity was 1.32 L
      preoperatively and 2.05 L at 1 year (a 56% improvement) (p < 0.001). CONCLUSIONS:
      This experience documents that patients with severely impaired lung function can
      successfully undergo operation for emphysema. To obtain these results one must
      tailor the operative approach to the patient's disease.

PMID- 8993264
TI  - Non-small cell lung cancer at the extremes of age: impact on diagnosis and
      treatment.
AB  - BACKGROUND: Early detection and surgical resection offers the highest likelihood
      of cure for patients with lung cancer. Patients presenting at the extremes of age
      may fail to benefit maximally from these interventions. To study the impact of
      age on stage, histology, symptom, and treatment of patients with non-small cell
      lung cancer, we undertook a retrospective review. METHODS: One thousand eight
      hundred two patients with non-small cell lung cancer were identified between 1983
      and 1993. Patients were selected by age as less than 45 years (55 patients) and
      80 years or more (108 patients), and their medical records were reviewed.
      RESULTS: Three younger patients (6%) presented with stage I or II disease, yet 15
      (32%) underwent thoracic operation. Twenty-seven elderly patients (33%) presented
      with early stage disease and only 6% underwent operation. The median survival was
      significantly longer for the younger population with surgically resectable stages
      of disease (stage I to IIIA) (p < 0.05), whereas no significant difference in
      survival was seen for the two groups with advanced disease (stage IIIB and IV).
      CONCLUSIONS: Age significantly affects the presentation and treatment of non
      small cell lung cancer patients. Although thoracic operation imparts the greatest
      survival advantage, this benefit is diminished due to advanced disease in the
      younger patients and lack of surgical intervention in the elderly.

PMID- 8993265
TI  - Right-to-left interatrial shunt after pneumonectomy.
AB  - BACKGROUND: Platypnea and Orthodeoxia have been described with congenital heart
      and severe lung diseases. METHODS: We report 4 patients in whom platypnea and
      orthodeoxia developed after pneumonectomy. In these patients the mean oxygen
      saturation on room air was 65% (range, 45% to 79%) in the supine position. On O2
      therapy it improved to 94% (range, 80% to 99%). When the patients assumed the
      erect position and were receiving O2 therapy the saturation dropped to a mean of
      76% (range, 56% to 82%) and the patients complained of shortness of breath.
      Cardiac catheterization revealed a mean pulmonary capillary wedge pressure of
      11.6 mm Hg (range, 7 to 18 mm Hg). All patients had normal right atrial pressure.
      A right-to-left interatrial shunt through a patent foramen ovale was documented
      by transesophageal echocardiography and dynamic ultrafast magnetic resonance
      imaging. The patients underwent surgical closure of the patent foramen ovale.
      RESULTS: In the erect position, the room air O2 saturation improved to a mean of
      95% (range, 92% to 99%), and the shortness of breath disappeared. CONCLUSIONS:
      Postpneumonectomy patients complaining of shortness of breath should be assessed
      for platypnea and orthodeoxia. A right-to-left interatrial shunt through a patent
      foramen ovale can occur even in the absence of elevated right heart pressures,
      especially after right pneumonectomy, and is accentuated in the upright posture.
      Surgical correction of the patent foramen ovale can produce dramatic improvement.

PMID- 8993266
TI  - Prolonged ischemia is associated with more pronounced rejection in the lung
      allograft.
AB  - BACKGROUND: Previously it was found that ischemia-reperfusion injury in a left
      lung autotransplantation model could be a minor inducer of major
      histocompatibility complex (MHC) class II antigen expression. Thus, we
      hypothesized that prolonged ischemic times may result in increased expression of
      MHC class II antigens and predispose the lungs to the development of acute
      rejection early after transplantation. METHODS: Twenty conditioned dogs underwent
      single left lung allotransplantation. Donor lungs were subjected to 4 or 24 hours
      (n = 10 each) of cold ischemia. Open lung biopsies, bronchoalveolar lavage fluid,
      and blood samples were taken preoperatively and at various intervals up to 1 week
      after transplantation. Lung biopsy specimens were examined histologically for MHC
      class II expression and graded for acute rejection. Bronchoalveolar lavage fluid
      and plasma were analyzed for cytokines interleukin-2 and interferon-gamma.
      RESULTS: In the 4-hour ischemia group, there was mild diffuse staining of the
      bronchial epithelium and cellular infiltrate for MHC class II antigens after 1
      week with subsequent grade 1-2 rejection. In the 24-hour ischemia group, MHC
      expression after 1 week revealed strong diffuse staining of bronchial epithelium,
      vascular endothelium, and cellular infiltrates with a significantly higher grade
      of rejection. Interleukin-2 and interferon-gamma significantly increased in BAL
      fluid early after transplantation in both groups. CONCLUSIONS: Ischemic injury
      may predispose the lung allograft to the development of acute rejection, in part,
      through the upregulation of MHC class II antigen expression and the local release
      of cytokines.

PMID- 8993267
TI  - Tracheal wire stent complications in malacia: implications of position and
      design.
AB  - BACKGROUND: Although expandable endoluminal wire stents that can be incorporated
      into body tissues are very attractive for use in the airway, disease-related
      factors that can lead to stent failure have received little attention in the
      literature. METHODS: The cases of all 4 patients who underwent insertion of one
      or more Gianturco stents into the trachea, main bronchi, or both for
      tracheobronchial malacia in our institution were reviewed. RESULTS: All three
      tracheal stents required removal for stent-related complications within the first
      6 months. Complications included metallic strut fracture and unraveling or
      breakage of the encircling nylon suture leading to progressively bizarre and
      widening radiographic configurations suggesting imminent airway perforation. One
      of the six bronchial stents disrupted 10 months after insertion. CONCLUSIONS: Our
      findings suggest relatively less dynamic, repetitive bending wire stress in the
      bronchus (and likewise strictured trachea) compared with the malacic trachea.
      Although Gianturco stents are easily placed and give excellent functional
      results, we recommend against their use in the trachea for tracheal malacia. The
      bronchial position may be reasonably safe.

PMID- 8993268
TI  - Radical resection of radiation-induced sarcoma of the chest wall: report of 15
      cases.
AB  - BACKGROUND: Surgical management of radiation-induced sarcoma of the chest wall
      remains difficult because of its impressive local aggressiveness. METHODS:
      Between 1987 and 1995, 15 patients (median age, 58 years) underwent radical
      resection of radiation-induced sarcoma of the chest wall. This type of tumor was
      defined as a metachronous, histologically different neoplasm in the irradiated
      field of the original tumor. Ten patients had a history of primary breast cancer
      and 5 patients, Hodgkin's disease. The median delivered radiation dose to the
      primary tumor area was 45 Gy, and the median interval between radiotherapy and
      diagnosis of sarcoma was 14 years. Seven tumors were located on the sternum,
      three on the lateral chest wall, and five in the thoracic outlet. Four total and
      three partial sternectomies, three lateral chest wall resections and five
      resections of tumors in the thoracic outlet (three first-rib resections) were
      performed. Seven patients required stabilization of the chest wall with
      prosthetic material. Soft tissue reconstruction was carried out with either
      muscle flaps and skin advancement in 9, musculocutaneous flaps in 4, or skin
      flaps alone in 2 patients. RESULTS: One patient died 3 months after total
      sternectomy of respiratory failure. Two patients (13.3%) had a local
      complication: sepsis after sternectomy in 1 and cutaneous necrosis in 1. Local
      recurrence occurred in 7 patients after a median interval of 10 months. Two of
      them died, and 4 underwent a repeat resection, 3 of whom are still alive. Four
      patients died of systemic recurrence. With a median follow-up of 30 months,
      overall 5-year survival and 5-year disease-free survival rates were 48% and 27%,
      respectively. CONCLUSION: Despite poor long-term disease-free survival, radical
      resection of radiation-induced sarcoma of the chest wall is justified on the
      basis of low postoperative morbidity and the lack of other available therapies.

PMID- 8993269
TI  - Severe deformity of a Palmaz-Schatz stent after normal surgical manipulation.
AB  - This report describes a case in which normal surgical manipulation during
      dissection of the heart while performing a repeat revascularization procedure
      produced a significant deformity in Palmaz-Schatz stents previously implanted in
      a saphenous vein graft. The graft had shown satisfactory angiographic appearance
      immediately before the operation, and consideration was given to leaving it in
      place. Its replacement, however, prevented a major intraoperative mishap.

PMID- 8993270
TI  - Visualization of ventricular fibroelastoma with a video-assisted thoracoscope.
AB  - Left ventricular papillary fibroelastomas are associated with a high risk of
      cerebral embolization. Two-dimensional echocardiography and intraoperative
      transesophageal echocardiography are helpful in diagnosing tumors, planning a
      surgical approach, and achieving adequate excision. A video-assisted thoracoscope
      via the left atrium was used to visualize a left ventricular papillary
      fibroelastoma. Thoracoscopic visualization facilitated excision of a mass within
      the chordae tendineae between the anterolateral papillary muscle and the left
      ventricular wall. Video-assisted thoracoscopy greatly facilitates
      exposure/excision of deeper intracavitary left ventricular masses.

PMID- 8993272
TI  - Aortic valve replacement via left thoracotomy after an esophageal operation.
AB  - Aortic valve replacement was performed through a left anterolateral thoracotomy
      using cardiopulmonary bypass in a 59-year-old man who had previously received
      esophageal resection with substernal reconstruction by gastric tube. Through this
      approach, injury of the reconstructed tube was avoided and the valve replacement
      operation was safely performed. We conclude that the lateral thoracotomy approach
      remains a valuable alternative for certain exceptional cases.

PMID- 8993271
TI  - Treatment of aortic dissection and ruptured abdominal aneurysm with coronary
      bypass.
AB  - We present a patient with a descending aortic dissection and contained rupture of
      a large abdominal aortic aneurysm with a history of inferior myocardial
      infarction and right coronary occlusion. The technique of combined repair of the
      descending thoracic aortic dissection with replacement of the ruptured infrarenal
      abdominal aorta and coronary artery bypass grafting is described.

PMID- 8993273
TI  - Danger of false intubation after traumatic tracheal transection.
AB  - Blunt tracheobronchial injuries may be difficult to diagnosis at presentation but
      can pose major airway difficulties. We present a patient with a tracheal
      transection who underwent intubation with the tip of the endotracheal tube
      exiting the trachea and terminating in the mediastinum adjacent to the distal
      trachea. He underwent surgical repair of the injury with end-to-end anastomosis.
      Although intubation over a flexible fiberoptic bronchoscope is desirable in cases
      of suspected tracheobronchial injury, it may not be feasible. In cases of
      suspected tracheobronchial injuries with blind endotracheal intubation, the
      possibility of false intubation should always be entertained.

PMID- 8993274
TI  - Correction of anomalous systemic venous drainage: transposition of left SVC to
      left PA.
AB  - In some patients, a persistent left superior vena cava drains into the left
      atrium (rather than the right) and may produce a symptomatic right-to-left shunt.
      We describe an extracardiac approach for correcting anomalous systemic venous
      drainage when the innominate vein is absent. In this technique, the left superior
      vena cava is transposed to the left pulmonary artery.

PMID- 8993275
TI  - Tracheal mucormycosis.
AB  - Pulmonary mucormycosis is a recognized entity occurring in diabetics and
      immunocompromised patients. It has a poor prognosis unless early diagnosis is
      made and appropriate surgical therapy instituted along with appropriate
      antifungal therapy. We describe here one of few cases of tracheal involvement by
      mucormycosis. Extensive destruction of the trachea and bibasal pneumonia led to
      the patient's death.

PMID- 8993276
TI  - Anomalous papillary muscle as a cause of left ventricular outflow tract
      obstruction in an adult.
AB  - Left ventricular outflow tract obstruction may be caused by abnormalities of the
      various structures comprised by the outflow tract. Hypertrophic cardiomyopathy is
      one of the more common causes, but many are rare anomalies, a collection of which
      we have compiled. We present a case of left ventricular outflow tract obstruction
      mimicking aortic stenosis in an adult. This was found to be due to abnormal
      insertion of a hypertrophied papillary muscle, successfully corrected by mitral
      valve replacement.

PMID- 8993277
TI  - Myxoma of the aortic valve.
AB  - Myxoma of the aortic valve is exceedingly uncommon. In this article, we report a
      58-year-old man with myxoma arising from the aortic valve. Aortic valve
      replacement was performed, and postoperative histologic examination showed myxoma
      of aortic valve.

PMID- 8993278
TI  - Early cardioverter defibrillator infection: value of indium-111 leukocyte
      imaging.
AB  - In the early postoperative period, it may be difficult to diagnose an infected
      implantable cardioverter-defibrillator system using anatomic imaging modalities
      such as computed tomography alone. We describe a case that illustrates the
      complementary physiologic role of indium-111-labeled leukocyte scintigraphy in
      identifying and defining the extent of early postoperative implantable
      cardioverter-defibrillator infection.

PMID- 8993279
TI  - Dual-inflow great vessel aneurysm: delayed presentation after penetrating trauma.
AB  - Aneurysms constitute uncommon sequelae of injuries to the thoracic outlet. Most
      such aneurysms are secondary to blunt trauma and usually involve the great
      vessels at their take-off from the aortic arch. Penetrating injuries are more
      often identified in the more distal vessels and only very rarely present as
      pseudoaneurysms. Reported here is a single case of a chronic posttraumatic
      pseudoaneurysm arising from both the right common carotid artery and the right
      subclavian artery. The workup and surgical approach provide practical lessons,
      complemented with illustrations that aid in the understanding of the case. It is
      an unusual case because of the dual-inflow nature of the aneurysm.

PMID- 8993281
TI  - Anaphylactic shock after aprotinin reexposure: time course of aprotinin-specific
      antibodies.
AB  - We report a case of severe anaphylactic shock during a cardiac operation that
      occurred as a consequence of aprotinin readministration in the presence of
      preformed aprotinin-specific antibodies. Both immunoglobulin G (3 hours) and
      immunoglobulin E (5 minutes) antibody levels dropped early after the clinical
      event. Despite their possibly limited clinical significance, we still recommend
      the conductance of specific antibody screening tests before readministration of
      aprotinin.

PMID- 8993280
TI  - Nonoperative management of tracheal laceration during endotracheal intubation.
AB  - Tracheal laceration is a rare but potentially devastating complication of
      endotracheal intubation. Traditional management of intubation-related tracheal
      laceration is operative. Nonoperative management of a woman noted to have a
      tracheal laceration during intubation is described. Criteria by which
      nonoperative treatment can be considered are outlined.

PMID- 8993282
TI  - Stent angioplasty for renovascular disease associated with acute aortic
      dissection.
AB  - Aortic replacement was performed in a patient with acute type A aortic dissection
      originating from the descending thoracic aorta. Postoperatively, a persistent
      false lumen resulted in severe stenosis of the right renal artery. Percutaneous
      stent angioplasty improved renovascular hypertension and renal function. This
      procedure is useful for management of patients with branch complications of
      aortic dissection.

PMID- 8993283
TI  - Transhiatal closure of right-sided esophageal rupture after a left pneumonectomy.
AB  - Right-sided spontaneous esophageal rupture developed 2 days after left
      pneumonectomy and vomiting. To avoid contamination of the pneumonectomized left
      thoracic cavity as well as a contralateral thoracotomy, we used a transhiatal
      approach for primary repair of the rupture, combined with right-sided pleural and
      mediastinal drainage, gastrostomy, and feeding jejunostomy. The 7-day barium meal
      control showed healing of the rupture.

PMID- 8993284
TI  - Cardiac tamponade after a systemic-pulmonary shunt complicated by serous leakage.
AB  - A newborn baby with complex congenital heart disease had severe persistent
      pericardial effusion after a systemic-pulmonary shunt. Pericardiocentesis and
      pericardiotomy could not stop pericardial leakage. At reoperation, topical
      application of a fibrin glue resulted in resolution of the leak and avoided
      replacement of the graft.

PMID- 8993285
TI  - Prevention of lower extremity ischemia during cardiopulmonary bypass via femoral
      cannulation.
AB  - Prolonged cardiopulmonary bypass requiring femoral arterial cannulation may lead
      to ipsilateral leg ischemia. A technique described of femoral cannulation via an
      end-to-side femoral artery graft allows distal femoral perfusion and eliminates
      the complication of leg ischemia.

PMID- 8993286
TI  - Forty-five-degree two-stage venous cannula: advantages over standard two-stage
      venous cannulation.
AB  - We present a 45-degree two-stage venous cannula that confers advantage to the
      surgeon using cardiopulmonary bypass. This cannula exits the mediastinum under
      the transverse bar of the sternal retractor, leaving the rostral end of the
      sternal incision free of apparatus. It allows for lifting of the heart with
      minimal effect on venous return and does not interfere with the radially laid out
      sutures of an aortic valve replacement using an interrupted suture technique.

PMID- 8993287
TI  - Patient position for a synchronous cervicothoracoabdominal two-team
      esophagectomy.
AB  - Cervicothoracoabdominal and cervicoabdominal approach are routinely adopted for
      total or subtotal esophagectomy. We propose a modification of the Nanson's
      patient position to optimize sequential or simultaneous left cervicotomy,
      laparotomy, and eventual right thoracotomy with one or two surgical teams. This
      technique permits better control of the operative field for each phase of the
      procedure with coordinated operating of two surgical teams on the neck, abdomen,
      and chest.

PMID- 8993288
TI  - Modified technique for heterotopic heart transplantation in small primates.
AB  - Cardiac transplantation in small primates represents a unique model for
      investigating both xenograft and allograft rejection. This report describes our
      technique for heterotopic transplantation of cardiac grafts into the
      retroperitoneal iliac vessels of newborn baboons and small primates. Small
      primates tolerate this position better than either cervical or abdominal
      placement.

PMID- 8993289
TI  - Two-directional aortic annular enlargement for aortic valve replacement in the
      small aortic annulus.
AB  - We have encountered 3 patients with a small aortic annulus for whom the
      conventional posterior enlargement alone was not extensive enough to implant an
      artificial valve of acceptable size. Therefore, we performed two-directional
      enlargement, which is a combination of posterior and anterior enlargement. First,
      the posterior enlargement was done, and then an additional aortotomy was made
      anteriorly and extended to the ventricular septum. The aortic annulus was
      enlarged by 68% after the two-directional enlargement. At a follow-up of 31
      months, the patients' functional status was New York Heart Association class I.

PMID- 8993290
TI  - John McCrae (1872-1918): doctor-soldier-poet.
AB  - Out of the ruins of World War I arose the poignant verse of the "Trench Poets."
      Lieutenant Colonel John McCrae, Canadian doctor, professor, and soldier,
      exemplified this verse in his haunting poem "In Flanders Fields." After
      establishing himself as a respected physician and university lecturer in Canada
      and the United States, he served in World War I as a physician and artillery
      commander. In 1918, after a grueling tour of duty, McCrae witnessed one of the
      Great War's most horrific technological creations: chemical warfare. He suffered
      from asthma and probable chronic obstructive pulmonary disease all his life,
      dying at age 45 of cerebral meningitis.

PMID- 8993291
TI  - Cytokine responses to cardiopulmonary bypass: lessons learned from cardiac
      transplantation.
AB  - BACKGROUND: A growing body of evidence relates the release during cardiopulmonary
      bypass (CPB) of proinflammatory cytokines, such as tumor necrosis factor-alpha,
      interleukin (IL)-6, and IL-8, to the postoperative systemic inflammatory response
      syndrome. Antiinflammatory cytokines, such as IL-10, however, may also play an
      important role in limiting these complications. METHODS: The English-language
      literature was reviewed. Emphasis was placed on cytokine responses during
      clinical CPB for cardiac operations and, in particular, for heart and heart-lung
      transplantation. RESULTS: The recent data indicate that (1) although cytokine
      release can be triggered by many factors during CPB, ischemia-reperfusion may
      play the most important role; (2) the levels of tumor necrosis factor-alpha, IL
      6, and IL-8 are correlated with the duration of cardiac ischemia and the
      myocardium is a major source of these three cytokines during CPB; (3) IL-10
      levels are correlated with the duration of CPB and the liver is a major source of
      IL-10 during CPB; and (4) steroid pretreatment is an effective intervention to
      inhibit the release of proinflammatory cytokines and enhance IL-10 production.
      CONCLUSIONS: The improved knowledge of cytokine responses to CPB may help to
      develop interventions aimed at reducing postoperative morbidity and mortality.

PMID- 8993293
TI  - Hypoplastic left heart syndrome.

PMID- 8993292
TI  - Endothelial cell injury in cardiovascular surgery: the systemic inflammatory
      response.
AB  - Many of the components currently used to perform cardiovascular operations lead
      to systemic insults that result from cardiopulmonary bypass circuit-induced
      contact activation, circulatory shock, and resuscitation, and a syndrome similar
      to endotoxemia. Experimental observations have demonstrated that these events
      have profound effects on activating endothelial cells to recruit neutrophils from
      the circulation. Once adherent to the endothelium, neutrophils release cytotoxic
      proteases and oxygen-derived free radicals, which are responsible for much of the
      end-organ damage seen after cardiovascular operations. Recently the cellular and
      molecular mechanisms of endothelial cell activation have become increasingly
      understood. It is conceivable that once the molecular mechanisms of endothelial
      cell activation are better defined, therapies will be developed allowing the
      selective or collective inhibition of vascular endothelial activation during the
      perioperative period.

PMID- 8993294
TI  - As originally published in 1989: New technique for repair of ascending thoracic
      aortic dissections. Updated in 1997.

PMID- 8993295
TI  - As originally published in 1989: Repair of large muscular ventricular septal
      defects in infants employing left ventriculotomy. Updated in 1996.

PMID- 8993296
TI  - The role of autologous pericardium in cardiac surgery.

PMID- 8993297
TI  - Cerebral oxygenation measured by near-infrared spectroscopy.

PMID- 8993299
TI  - Right atrial metastatic melanoma.

PMID- 8993300
TI  - Modification in the Carpentier retractor.

PMID- 8993298
TI  - Cerebral oxygenation measured by near-infrared spectroscopy.

PMID- 8993301
TI  - Physiology and biomechanics of intraaortic balloon pumping.

PMID- 8993303
TI  - Maximal use of internal mammary artery.

PMID- 8993302
TI  - Protection of the retrosternal right internal mammary artery with stented grafts.

PMID- 8993304
TI  - Magnesium sulfate to facilitate weaning of nitric oxide in pulmonary
      hypertension.

PMID- 8993305
TI  - Additional insights into combined surfactant and nitric oxide therapy.

PMID- 8993306
TI  - Background mortality and aortic valve replacement in the elderly.

PMID- 8993307
TI  - Developments in surgical palliation of univentricular physiology.

PMID- 8993308
TI  - Coronary artery bypass in a patient with pernicious anemia.

PMID- 8993309
TI  - Operation for pectus excavatum.

PMID- 8993310
TI  - Internal thoracic artery pedicle hematoma management with radial artery
      extension.

PMID- 8993311
TI  - General concept for ion translocation by halobacterial retinal proteins: the
      isomerization/switch/transfer (IST) model.
AB  - Bacteriorhodopsin (BR), which transports protons out of the cell in a light
      driven process, is one of the best-studied energy-transducing proteins. However,
      a consensus on the exact molecular mechanism has not been reached. Matters are
      complicated by two experimental facts. First, recent results using BR mutants (BR
      D85T) and the homologous protein sensory rhodopsin I demonstrate that the
      vectoriality of active proton transport may be reversed under appropriate
      conditions. Second, in BR-D85T as well as in the homologous halorhodopsin,
      protons and chloride ions compete for transport; e.g. the same molecule may
      transport either a positive or a negative ion. To rationalize these results, we
      propose a general model for ion translocation by bacterial rhodopsins which is
      mainly based on two assumptions. First, the isomerization state of the
      retinylidene moiety governs the accessibility of the Schiff base in the protein;
      e.g. all-trans, 15-anti, and 13-cis-15-anti direct the Schiff base to
      extracellular and cytoplasmic accessibility, respectively, but change in
      accessibility (called the "switch") is a time-dependent process in the
      millisecond time range. A light-induced change of the isomerization state induces
      not only a change in accessibility but also an ion transfer reaction. Second, we
      propose that these two processes are kinetically independent, e.g. that relative
      rate constants in a given molecule determine which process occurs first,
      ultimately defining the vectoriality of active transport.

PMID- 8993312
TI  - Active site mutants implicate key residues for control of color and light cycle
      kinetics of photoactive yellow protein.
AB  - To understand how the protein and chromophore components of a light-sensing
      protein interact to create a light cycle, we performed time-resolved spectroscopy
      on site-directed mutants of photoactive yellow protein (PYP). Recently determined
      crystallographic structures of PYP in the ground and colorless I2 states allowed
      us to design mutants and to study their photosensing properties at the atomic
      level. We developed a system for rapid mutagenesis and heterologous bacterial
      expression for PYP apoprotein and generated holoprotein through formation of a
      covalent thioester linkage with the p-hydroxycinnamic acid chromophore as found
      in the native protein. Glu46, replaced by Gln, is buried in the active site and
      hydrogen bonds to the chromophore's phenolate oxygen in the ground state. The
      Glu46Gln mutation shifted the ground state absorption maximum from 446 to 462 nm,
      indicating that the color of PYP can be fine-tuned by the alteration of hydrogen
      bonds. Arg52, which separates the active site from solvent in the ground state,
      was substituted by Ala. The smaller red shift (to 452 nm) of the Arg52Ala mutant
      suggests that electrostatic interactions with Arg52 are not important for charge
      stabilization on the chromophore. Both mutations cause interesting changes in
      light cycle kinetics. The most dramatic effect is a 700-fold increase in the rate
      of recovery to the ground state of Glu46Gln PYP in response to a change in pH
      from pH 5 to 10 (pKa = 8). Prompted by this large effect, we conducted a careful
      reexamination of pH effects on the wild-type PYP light cycle. The rate of color
      loss decreased about 3-fold with increasing pH from pH 5 to 10. The rate of
      recovery to the colored ground state showed a bell-shaped pH dependence,
      controlled by two pKa values (6.4 and 9.4). The maximum recovery rate at pH 7.9
      is about 16 times faster than at pH 5. The effect of pH on Arg52Ala is like that
      on wild type except for faster loss of color and slower recovery. These kinetic
      effects of the mutations and the changes with pH demonstrate that both phases in
      PYP's light cycle are actively controlled by the protein component.

PMID- 8993313
TI  - Crystal structure of bovine low molecular weight phosphotyrosyl phosphatase
      complexed with the transition state analog vanadate.
AB  - The early transition metal oxoanions vanadate, molybdate, and tungstate are
      widely used inhibitors for phosphatase enzymes. These oxoanions could inhibit
      such enzymes by simply mimicking the tetrahedral geometry of phosphate ion.
      However, in some cases, the enzyme-inhibitor dissociation constants (Ki) for
      these oxoanions are much lower than that for phosphate. Such observations gave
      rise to the hypothesis that in some cases these transition metal oxoanions may
      inhibit phosphomonoesterases by forming complexes that resemble the trigonal
      bipyramidal geometry of the SN2(P) transition state. As a test of this, the
      crystal structures of a low molecular weight protein tyrosine phosphatase at pH
      7.5 complexed with the inhibitors vanadate and molybdate were solved at 2.2 A
      resolution and compared to a newly refined 1.9 A structure of the enzyme.
      Geometric restraints on the oxoanions were relaxed during refinement in order to
      minimize model bias. Both inhibitors were bound at the active site, and the
      overall protein structures were left unchanged, although some small but
      significant side chain movements at the active site were observed. Vanadate ion
      formed a covalent linkage with the nucleophile Cys12 at the active site and
      exhibited a trigonal bipyramidal geometry. In contrast, simple tetrahedral
      geometry was observed for the weaker molybdate complex. These studies are
      consistent with the conclusion that vanadate inhibits tyrosine phosphatases by
      acting as a transition state analog. The structure of the vanadate complex may be
      expected to closely resemble the transition state for reactions catalyzed by
      protein tyrosine phosphatases.

PMID- 8993314
TI  - Reaction mechanism of Escherichia coli dihydrodipicolinate synthase investigated
      by X-ray crystallography and NMR spectroscopy.
AB  - Dihydrodipicolinate synthase (DHDPS) catalyzes the condensation of pyruvate with
      L-aspartate beta-semialdehyde. It is the first enzyme unique to the
      diaminopimelate pathway of lysine biosynthesis. Here we present the crystal
      structures of five complexes of Escherichia coli DHDPS with substrates, substrate
      analogs, and inhibitors. These include the complexes of DHDPS with (1) pyruvate,
      (2) pyruvate and the L-aspartate beta-semialdehyde analog succinate beta
      semialdehyde, (3) the inhibitor alpha-ketopimelic acid, (4) dipicolinic acid, and
      (5) the natural feedback inhibitor L-lysine. The kinetics of inhibition were
      determined, and the binding site of the L-lysine was identified. NMR experiments
      were conducted in order to elucidate the nature of the product of the reaction
      catalyzed by DHDPS. By this method, (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)
      dipicolinic acid is identified as the only product. A reaction mechanism for
      DHDPS is proposed, and important features for inhibition are identified.

PMID- 8993315
TI  - Active site directed mutagenesis of 3 beta/17 beta-hydroxysteroid dehydrogenase
      establishes differential effects on short-chain dehydrogenase/reductase
      reactions.
AB  - Mutagenetic replacements of conserved residues within the active site of the
      short-chain dehydrogenase/reductase (SDR) superfamily were studied using
      prokaryotic 3 beta/17 beta-hydroxysteroid dehydrogenase (3 beta/17 beta-HSD) from
      Comamonas testosteroni as a model system. The results provide novel data to
      establish Ser 138 as a member of a catalytically important "triad" of residues
      also involving Tyr151 and Lys155. A Ser-->Ala exchange at position 138 results in
      an almost complete (> 99.9%) loss of enzymatic activity, which is not observed
      with a Ser-->Thr replacement. This indicates that an essential factor for
      catalysis is the ability of side chain 138 to form hydrogen bond interactions.
      Mutations in the NAD(H) binding region, in strands beta A, beta D, and adjacent
      turns, reveal two additional residues, Thr12 and Asn87, which are important for
      correct binding of the coenzyme and with a differential effect on the reactions
      catalyzed. Thus, mutation of Thr12 to Ala results in a complete loss of the 3
      beta-dehydrogenase activity, whereas the 3-oxoreductase activity remains
      unchanged. On the other hand, a T12S substitution yields a protein with unaltered
      catalytic constants for both reactions, revealing that a specific hydrogen bond
      is critical for the dehydrogenase activity. Our interpretation of the available
      crystal structure of 3 alpha/20 beta-HSD from Streptomyces hydrogenans suggests a
      hydrogen bond in that enzyme between the Thr12 side chain and the backbone NH of
      Asn87 rather than the coenzyme, indicating that this hydrogen bond to the beta D
      strand might determine a crucial difference between the reductive and the
      oxidative reaction types. Similarly, mutation of Asn87 to Ala results in an 80%
      reduction of kcat/Km in the dehydrogenase direction but also unchanged 3
      oxoreductase properties. It appears that the binding of NAD+ to the protein is
      influenced by local structural changes involving strand beta D and turn beta A to
      alpha B.

PMID- 8993316
TI  - An exposed tyrosine on the surface of trimethylamine dehydrogenase facilitates
      electron transfer to electron transferring flavoprotein: kinetics of transfer in
      wild-type and mutant complexes.
AB  - In wild-type trimethylamine dehydrogenase, tyrosine-442 is located at the center
      of a concave region on the surface of the enzyme that is proposed to form the
      docking site for the physiological redox acceptor, electron transferring
      flavoprotein. The intrinsic rate constant for electron transfer in the
      reoxidation of one-electron dithionite-reduced wild-type trimethylamine
      dehydrogenase (modified with phenylhydrazine) by electron transferring
      flavoprotein was investigated by stopped-flow spectroscopy. Analysis of the
      temperature dependence of the reaction rate by electron transfer theory yielded
      values for the reorganizational energy of 1.4 eV and the electronic coupling
      matrix element of 0.82 cm-1. The role played by residue Tyr-442 in facilitating
      reduction of ETF by TMADH was investigated by isolating three mutant forms of the
      enzyme in which Tyr-442 was exchanged for a phenylalanine, leucine, or glycine
      residue. Rates of electron transfer from these mutants of TMADH to ETF were
      investigated by stopped-flow spectroscopy. At 25 degrees C, modest reductions in
      rate were observed for the Y442F (1.4-fold) and Y442L (2.2-fold) mutant
      complexes, but a substantial decrease in rate (30.5-fold) and an elevated
      dissociation constant for the complex were seen for the Y442G mutant enzyme.
      Inspection of the crystal structure of wild-type TMADH reveals that Tyr-442 is
      positioned along one side of a small cavity on the surface of the enzyme: Val
      344, located at the bottom of this cavity, is the closest surface residue to the
      4Fe-4S center of TMADH and is likely to be positioned on a major electron
      transfer pathway to ETF. The reduced electron transfer rates in the mutant
      complexes are probably brought about by decreases in electronic coupling between
      the electron transfer donor and acceptor within the complex, either directly or
      indirectly due to unfavorable change in the orientation of the two proteins with
      respect to one another.

PMID- 8993317
TI  - Analysis of binding interactions in an idiotope-antiidiotope protein-protein
      complex by double mutant cycles.
AB  - The idiotope-antiidiotope complex between the anti-hen egg white lysozyme
      antibody D1.3 and the anti-D1.3 antibody E5.2 provides a useful model for
      studying protein-protein interactions. A high-resolution crystal structure of the
      complex is available [Fields, B. A., Goldbaum, F. A., Ysern, X., Poljak, R.J., &
      Mariuzza, R. A. (1995) Nature 374, 739-742], and both components are easily
      produced and manipulated in Escherichia coli. We previously analyzed the relative
      contributions of individual residues of D1.3 to complex stabilization by site
      directed mutagenesis [Dall'Acqua, W., Goldman, E. R., Eisenstein, E., & Mariuzza,
      R. A. (1996) Biochemistry 35, 9667-9676]. In the current work, we introduced
      single alanine substitutions in 9 out of 21 positions in the combining site of
      E5.2 involved in contacts with D1.3 and found that 8 of them play a significant
      role in ligand binding (delta Gmutant-delta Gwild type > 1.5 kcal/mol).
      Furthermore, energetically important E5.2 and D1.3 residues tend to be juxtaposed
      in the crystal structure of the complex. In order to further dissect the
      energetics of specific interactions in the D1.3-E5.2 interface, double mutant
      cycles were carried out to measure the coupling of 13 amino acid pairs, 9 of
      which are in direct contact in the crystal structure. The highest coupling energy
      (4.3 kcal/mol) was measured for a charged-neutral pair which forms a buried
      hydrogen bond, while side chains which interact through solvated hydrogen bonds
      have lower coupling energies (1.3-1.7 kcal/mol), irrespective of whether they
      involve charged-neutral or neutral-neutral pairs. Interaction energies of similar
      magnitude (1.3-1.6 kcal/mol) were measured for residues forming only van der
      Waals contacts. Cycles between distant residues not involved in direct contacts
      in the crystal structure also showed significant coupling (0.5-1.0 kcal/mol).
      These weak long-range interactions could be due to rearrangements in solvent or
      protein structure or to secondary interactions involving other residues.

PMID- 8993318
TI  - Site-directed mutagenesis of alpha II spectrin at codon 1175 modulates its mu
      calpain susceptibility.
AB  - Intracellular proteolysis by the calpains, a family of Ca2+ activated cysteine
      proteases, is a ubiquitous yet poorly understood process. Their action is
      implicated in an array of cellular and pathologic processes, including long-term
      potentiation, synaptic remodeling, protein kinase C and steroid receptor
      activation, ischemic cellular injury, and apoptosis. Unlike most proteases, the
      calpains display unusually strict substrate specificity, often cleaving only one
      or two bonds in proteins with hundreds of potential sites. Studies of synthetic
      peptides have defined sequences that modulate their specificity, but little data
      exist in the context of a bona fide protein. A prominent substrate for mu-calpain
      is alpha II spectrin (fodrin, brain spectrin), which is cleaved between Tyr1176
      and Gly1177 within spectrin's 11th structural repeat unit. We have cloned and
      characterized human fetal brain alpha II spectrin (GenBank no. U26396) and
      identified a new Thr1300 to Ile polymorphism. From this clone, recombinant GST
      fusion proteins representing repeat units 8-14 have been prepared and used to
      systematically explore the in vitro determinants of mu-calpain sensitivity.
      Twenty different amino acids were substituted by site-directed mutagenesis for
      wild-type Val1175, the penultimate (P2) residue flanking the major calpain
      cleavage site in alpha II spectrin. Gly, Pro, and Asp, and to a lesser extent Phe
      and Glu, substantively inhibited the susceptibility of this site to mu-calpain;
      other substitutions yielded lesser effects. Dynamic molecular modeling of the
      11th structural repeat of human alpha II spectrin incorporating the various
      mutations suggests that the calpain cleavage site with its flanking calmodulin
      binding domain interrupts helix C of alpha II spectrin's 11th repetitive unit
      without significantly disrupting the repeat's triple-helical motif. This model
      predicts that the critical Tyr1176-Gly1177 bond occurs in a highly exposed loop
      juxtaposed between helix C and the calmodulin binding domain and that mutations
      at the P2 position subtly alter the conformation about this site. We conclude
      that secondary and tertiary conformational features surrounding the cleavage
      site, rather than the linear sequence itself, dominate the determinants that
      define alpha II spectrin's mu-calpain susceptibility.

PMID- 8993319
TI  - Sterically stabilized anti-HER2 immunoliposomes: design and targeting to human
      breast cancer cells in vitro.
AB  - Liposomes (70-100 nm) of 1-palmitoyl-2-oleoylphosphatidylcholine, cholesterol,
      and poly(ethylene glycol) (PEG)-modified phosphatidylethanolamine (PEG-DSPE) were
      conjugated to Fab' fragments of a humanized recombinant MAb against the
      extracellular domain of HER2/neu to create sterically stabilized immunoliposomes
      (anti-HER2 SL) as a drug carrier targeting HER2-overexpressing cancers.
      Conjugation employed maleimide-terminated membrane-anchored spacers of two kinds:
      a short spacer, providing attachment of Fab' close to the liposome bilayer, or a
      long spacer, with Fab' attachment at the distal terminus of the PEG chain.
      Confocal microscopy and spectrofluorometry of HER2-overexpressing breast cancer
      cells incubated with fluorescently labeled anti-HER2 SL prepared with either
      spacer showed binding of liposomes (8000-23000 vesicles/cell) followed by
      endocytosis (rate constant ke = 0.012-0.033 min-1) via the coated-pit pathway,
      evidenced by intracellular acidification and colocalization with transferrin.
      Uptake of anti-HER2 immunoliposomes by breast cancer cells with low HER2
      expression, or after preincubation of cells with free anti-HER2 Fab', was less
      than 0.2% and 4.3%, respectively, of the uptake by HER2-overexpressing cells.
      Increasing PEG-DSPE content (up to 5.7 mol %) in anti-HER2-SL prepared with the
      short spacer decreased liposome-cell binding affinity 60-100-fold, while ke
      decreased only 2-fold; however, when Fab' fragments were conjugated via a PEG
      spacer, both binding affinity and ke were unaffected by PEG-DSPE content. Cell
      binding and internalization of anti-HER2 immunoliposomes increased at higher
      surface density of conjugated Fab' fragments, reaching plateaus at approximately
      40 Fab'/liposome for binding and approximately 10-15 Fab'/liposome for
      internalization. Uptake of anti-HER2 immunoliposomes correlated with the cell
      surface density of HER2 and significantly (p < 0.005) correlated with the
      antiproliferative effect of the targeting antibody but not with the total level
      of cellular HER2 expression. The results obtained were used to optimize in vivo
      preclinical studies of anti-HER2 SL loaded with antineoplastic drugs.

PMID- 8993320
TI  - Photochemical reactions of photosystem II in ethylene glycol.
AB  - The behavior of photosystem II (PSII) reactions was investigated under conditions
      of decreasing water content by the addition of increasing concentrations of
      ethylene glycol (EG). The photosynthetic activities were measured for PSII
      samples either directly in aqueous solutions of EG or in the standard buffer
      medium following EG treatment. Several effects on PSII arise upon exposure to EG.
      Below 50% EG there are no significant irreversible changes, although there is a
      slowing of the QA-reoxidation kinetics in the presence of EG. At concentrations
      of 50-70% EG, protein structural changes occur that include the release of the
      16, 23, and 33 kDa extrinsic proteins and two of the catalytic Mn ions. For these
      samples, the capacity for O2 evolution is considerably reduced and the formation
      of donor side H2O2 is enhanced. In 60% EG, the nanosecond components in the rate
      of P680+ reduction are converted entirely to microsecond kinetics which upon
      return of the sample to the standard buffer medium are partially restored,
      indicating that EG has a reversible, solvent effect on the PSII donor side. At
      concentrations of EG > 70% chlorophyll fluorescence measurements reveal
      reversible increases in the FO level concomitant with the generation and
      disappearance of a 5 microseconds decay component in the P680+ reduction
      kinetics. This result may indicate a solvent-induced uncoupling of the light
      harvesting pigment bed from the reaction center complex. As the EG concentration
      is increased to 80-100%, there is an irreversible loss of the primary charge
      separation. The use of EG as a cryoprotectant and as a water-miscible organic
      solvent for PSII is discussed.

PMID- 8993321
TI  - Electron paramagnetic resonance kinetic studies of the S states in spinach
      thylakoids.
AB  - The Tyrz+ decay kinetics have been analyzed by using time-resolved EPR to
      determine the half-time of each Si-->S(i + 1) transition in the O2-evolving
      complex of spinach thylakoids under physiological conditions. Using dark-adapted
      thylakoids and appropriate single-turnover flash sequences, we were able to
      detect the signal IIvf kinetics of the Tyrz+ S0-->Tyrz S1, Tyrz+ S1-->Tyrz S2,
      Tyrz+ S2-->Tyrz S3, and Tyrz+ S3-->(S4)-->Tyrz S0 transitions. To correct for
      damping of the S state synchronization during the flash sequence, the Kok
      parameters were estimated by measuring the oxygen flash pattern in situ using
      nitroxide-based EPR oximetry. Following deconvolution of the individual S state
      contributions, the signal IIvf decay kinetics yield the following half-times for
      the S state transitions: S0-->S1 in 40-60 microseconds, S1-->S2 in 85
      microseconds, S2-->S3 in 140 microseconds, and S3-->(S4)-->S0 in 750
      microseconds. Preliminary results with detergent-solubilized PSII membranes
      suggest that the S3-->S0 transition at least is slowed by a factor of
      approximately 2 in this system. Ramifications of these half-times in terms of
      electron transfer events on the donor site of PSII are discussed.

PMID- 8993322
TI  - Targeted mutations in the psaC gene of Chlamydomonas reinhardtii: preferential
      reduction of FB at low temperature is not accompanied by altered electron flow
      from photosystem I to ferredoxin.
AB  - The terminal part of the electron pathway within the photosystem I (PSI) complex
      includes two [4Fe-4S] centers, FA and FB, which are coordinated by the PsaC
      subunit. To gain new insights into the electron transfer mechanisms through PsaC,
      we have generated three mutant strains of the alga Chlamydomonas reinhardtii in
      which two positively charged residues, K52 and R53, near the FA center have been
      altered in different ways. The mutations K52S/R53D and K52P/R53D lead to a strong
      destabilization of PSI. The third mutant K52S/R53A accumulates PSI to 30% of wild
      type levels and shares the same residues between two of the cysteine ligands of
      FA as the PsaC homologue in the green sulfur bacterium Chlorobium limicola, in
      which FB has a higher redox potential than FA [Nitschke, W., Feiler, U., &
      Rutherford, A. W. (1990) Biochemistry 29, 3834-3842]. Low-temperature electron
      paramagnetic resonance (EPR) studies reveal that, in contrast to wild type, FB is
      preferentially photoreduced in this mutant, as was also observed for C. limicola.
      The preferential photoreduction of FB could be due to changes in the redox
      potential of FA and/or to slight structural modifications of the PsaC subunit.
      However, room temperature optical measurements show that stable charge separation
      still occurs and, surprisingly, that electron transfer from PSI to ferredoxin
      proceeds at normal rates in the mutant. As C. limicola, the K52S/R53A and
      K52S/R53D C. reinhardtii mutants are photosensitive when grown aerobically, but
      can grow photoautotrophically under anaerobic conditions.

PMID- 8993323
TI  - Recombinant type A and B phytochromes from potato. Transient absorption
      spectroscopy.
AB  - The cDNAs encoding full-length type A and B phytochromes (phyA and phyB,
      respectively) from potato were expressed in inducible yeast systems
      (Saccharomyces cerevisiae and Pichia pastoris). In addition, a deletion mutant of
      phyB (delta 1-74) was expressed. The apoproteins were reconstituted into
      chromoproteins by incorporation of the native chromophore, phytochromobilin (P
      phi B), and of phycocyanobilin (PCB). The incorporation of P phi B yielded
      chromoproteins with difference absorptions lambda max at 660 and 712 nm (Pr and
      Pfr, respectively) for phyA, and at 665 and 723 nm for phyB. All difference
      maxima of PCB phytochromes are blue-shifted by several nanometers with respect to
      those obtained with the P phi B chromophore. The deletion construct with PCB
      shows difference absorption maxima at 652 and 705 nm with the Pfr absorbance
      considerably reduced. Time-resolved kinetic analysis of a phyB-type phytochrome
      by nanosecond flash photolysis was performed for the first time. Recombinant full
      length phyB afforded transient absorbance changes similar (but not identical) to
      those of phyA from Avena, whereas the kinetic behavior of these intermediates was
      very different. Contrary to phyA from Avena, the I700 intermediate from phyB
      reconstituted with either PCB or P phi B decayed following single exponential
      kinetics with a lifetime of 87 or 84 microseconds, respectively, at 10 degrees C.
      The formation of Pfr of PCB-containing recombinant phyB (phyB-PCB) could be
      fitted with three lifetimes of 9, 127, and 728 ms. The corresponding lifetimes of
      phyB-P phi B are 22.5, 343, and 2083 ms. Whereas for phyB-PCB all three
      millisecond lifetimes are related to the formation of Pfr, the 2 s component of
      phyB-P phi B is concomitant with a rapid recovery of Pr. For recombinant potato
      phyA and delta 1-74 phyB, no time-resolved data could be obtained due to the
      limited quantities available. As described for phytochromes of other
      dicotelydons, the Pfr forms of full-length phyA and PhyB of potato underwent
      rapid dark conversion to Pr.

PMID- 8993324
TI  - Origin of the photoacoustic signal in cytochrome P-450cam: role of the Arg186
      Asp251-Lys178 bifurcated salt bridge.
AB  - The origin of the photoacoustic signal in ferrous CO-camphor-cytochrome P-450cam
      was investigated. Recently, the Arg186-Asp251-Lys178 bifurcated salt bridge,
      located above the heme pocket, has been shown to play a key role in the control
      of the diffusion step of camphor binding [Deprez, E., Gerber, N. C., Di Primo,
      C., Douzou, P., Sligar, S. G., & Hui Bon Hoa, G. (1994) Biochemistry 33, 14464
      14468]. We considered the hypothesis that electrostriction resulting from the
      transient exposure of these charged residues to the solvent could be responsible
      for part of the photoacoustic signal. We thus examined the effects of a site
      directed mutation of these linkages and ionic strength increases. Upon
      replacement of the Asp251 residue by an asparagine residue, the overall enthalpy
      and volume change of the CO dissociation reaction decrease from -5 to -24
      kcal/mol and from 11 to 5.4 mL/mol, respectively. The mutation has the same
      effect on the thermodynamic parameters as increasing the ionic strength of the
      medium over a range of potassium or sodium concentrations from 0 to 500 mM. For
      the D251N mutant, the overall enthalpy of the reaction does not change with the
      ionic strength whereas a small effect is observed on the volume change. The
      results indicate that electrostriction around the bifurcated salt bridge
      contributes to the photoacoustic signal and suggest a scheme in which, following
      photodissociation of CO and diffusion of the molecule through the protein matrix,
      the structure relaxes and the bifurcated salt bridge desolvates.

PMID- 8993325
TI  - A lysine 73-->histidine variant of yeast iso-1-cytochrome c: evidence for a
      native-like intermediate in the unfolding pathway and implications for m value
      effects.
AB  - In this paper we report thermodynamic studies on a variant of yeast iso-1
      cytochrome c in which a surface lysine residue at position 73 has been replaced
      with a histidine (H73). Guanidine hydrochloride denaturation studies monitored by
      circular dichroism spectroscopy indicated decreased thermodynamic stability (a
      lower delta G(o)(u)H20) and a smaller m value for the H73 protein as compared to
      the wild type (WT) protein. Further investigations to probe the causes for the
      thermodynamic stability differences between the two proteins involved guanidine
      hydrochloride and urea denaturations monitored by tryptophan fluorescence. The
      stability of heme ligation in the denatured state in the presence of either
      guanidine hydrochloride or urea was monitored by the spin-state transition of the
      heme iron induced by pH. None of these studies supported the hypothesis that the
      decreased m value was due to heme-His73 ligation in the denatured state.
      Guanidine hydrochloride denaturations monitored by the change in the extinction
      coefficient at 695 nm, which is sensitive to the presence of heme-Met80 ligation,
      revealed a native-like intermediate for the H73 protein, probably caused by
      displacement of the Met80 heme ligand by histidine 73 at guanidine hydrochloride
      concentrations much lower than required for full cooperative unfolding. Presence
      of the native-like intermediate is most likely the cause of the smaller m value
      and decreased thermodynamic stability for the CD-monitored H73 protein unfolding
      as compared to the unfolding of the WT protein. Guanidine hydrochloride
      denaturations in the presence of 200 mM imidazole provide further evidence in
      support of the proposed mechanism.

PMID- 8993327
TI  - Roles of efficient substrates in enhancement of peroxidase-catalyzed oxidations.
AB  - Efficient peroxidase substrates may have a critical role in the oxidation of
      secondary compounds by peroxidases. Hydrazines are often oxidized slowly by
      peroxidases due, in part, to hydrazine-dependent inactivation of these enzymes.
      Peroxidase-catalyzed oxidation of hydrazines may be dramatically affected by an
      efficient peroxidase substrate. We investigated this hypothesis in a model system
      using the well-known peroxidase substrate chlorpromazine (CPZ) and the hydrazine
      derivative isoniazid. CPZ stimulated isoniazid oxidation as measured by nitroblue
      tetrazolium (NBT) reduction and O2 consumption. The kinetics of isoniazid and CPZ
      oxidation by horseradish peroxidase (HRP) in the presence of both compounds
      suggested CPZ was acting as an electron transfer mediator between HRP and
      isoniazid. Indeed, CPZ.+, the product of CPZ oxidation by HRP, was able to
      oxidize isoniazid. The rate constant for this pH-dependent reaction was (2.6 +/-
      0.1) x 10(4) M-1 s-1 at pH 4.5. In the absence of CPZ, isoniazid-dependent
      irreversible inactivation of HRP was observed. The inactivation process involved
      the formation of compound III followed by accumulation of irreversibly
      inactivated HRP. CPZ completely inhibited inactivation. Thus, by acting as a
      redox mediator and preventing HRP inactivation, CPZ stimulated isoniazid
      oxidation by several orders of magnitude. Similarly, other efficient peroxidase
      substrates, such as phenol and tyrosine, were also able to dramatically stimulate
      isoniazid oxidation by HRP. We suggest that the presence of efficient peroxidase
      substrates may potentiate the activation of isoniazid and other hydrazines. As
      such, these substrates may have a vital role in the pharmacological and
      toxicological properties of hydrazines and other compounds.

PMID- 8993326
TI  - Interaction of Escherichia coli cobalamin-dependent methionine synthase and its
      physiological partner flavodoxin: binding of flavodoxin leads to axial ligand
      dissociation from the cobalamin cofactor.
AB  - Cobalamin-dependent methionine synthase from Escherichia coli catalyzes the last
      step in de novo methionine biosynthesis. Conversion of the inactive cob(II)alamin
      form of the enzyme, formed by the occasional oxidation of cob(I)alamin during
      turnover, to an active methylcobalamin-containing form requires a reductive
      methylation of the cofactor in which an electron is supplied by reduced
      flavodoxin and the methyl group is derived from S-adenosyl-L-methionine. E. coli
      flavodoxin acts specifically in this activation reaction, and neither E. coli
      ferredoxin nor flavodoxin from the cyanobacterium Synechococcus will substitute,
      despite their highly similar midpoint potentials for one-electron transfer. As
      assessed by EPR spectroscopy, the binding of flavodoxin to cob(II)alamin
      methionine synthase results in a change in the coordination geometry of the
      cobalt from five-coordinate to four-coordinate. Histidine 759 of methionine
      synthase, which replaces the normal lower ligand dimethylbenzimidazole on binding
      of methylcobalamin to methionine synthase, is dissociated from the cobalt of the
      cobalamin by the binding of flavodoxin. The association of flavodoxin and
      methionine synthase depends on ionic strength and pH; the pH dependence
      corresponds to the uptake of one proton on association. The formation of a
      complex between flavodoxin and methionine synthase perturbs the midpoint
      potentials of the flavin and cobalamin cofactors only marginally and without any
      significant thermodynamic advantage for electron transfer to the cobalamin of
      methionine synthase. No significant binding was seen between oxidized flavodoxin
      and methylcobalamin methionine synthase. A model for the interaction of
      methionine synthase with flavodoxin is proposed in which flavodoxin binding leads
      to changes in the distribution of methionine synthase conformations.

PMID- 8993328
TI  - Identification of the pH sensor for nucleotide binding in the uncoupling protein
      from brown adipose tissue.
AB  - The transport inhibiting nucleotide binding to the uncoupling protein (UCP) has a
      unique pH dependence and has been postulated to be controlled by the dissociation
      state of a carboxyl group in UCP with pK 4.5 and, in addition only for the
      nucleoside triphosphate, by a group with pK 7.2. To prove this assumption and to
      identify the carboxyl group, Woodward reagent K (WRK) was applied to UCP. In
      mitochondria, WRK was found to inhibit binding of GTP in a noncompetitive manner
      using WRK in the millimolar range. In isolated UCP, GTP binding is inhibited by
      WRK at a 1 to 2 ratio to UCP, suggesting that WRK primarily reacts with only one
      carboxyl group. Prebound GTP protects against WRK reaction as monitored by GTP
      binding. The protection decreases from pH 5 to 7 due to better reactivity of WRK
      and less tight GTP binding. WRK does not inhibit H+ transport by UCP but prevents
      GTP inhibition of H+ transport. For elucidating the WRK target residue, the WRK
      derivatized group was labeled with [3H] by reduction with [3H]NaBH4. Both GTP and
      GDP largely protected against WRK-dependent [3H] labeling. CNBr fragmentation
      identified the region T121-M197 as the [3H] incorporation site. Combined CNBr and
      tryptophane cleavage by the reagent 3-bromo-3-methyl-2-((2-nitrophenyl) thio)-3H
      indole (BNPS) allowed to further delimit the 2.8 kDa peptide W173-M197 as the
      [3H] label carrier which contains two acid residues E190 and D195. To further
      identify the residue, limited tryptic digestion in sarcosyl-treated UCP was
      performed, and a tryptic fragment enclosing E190 and D195 was isolated which
      carried most of the [3H] label. Edman degradation showed the major [3H] label at
      the eighth position corresponding to E190 and no peak at D195. Thus, the original
      postulate of the pH-sensing carboxyl group regulating both the nucleoside di- and
      triphosphate binding has been verified. It is identified as E190 situated in the
      fourth transmembrane helix. In total, now four residues close to the nucleotide
      binding sites in UCP have been determined.

PMID- 8993329
TI  - A novel metalloprotease in rat brain cleaves the amyloid precursor protein of
      Alzheimer's disease generating amyloidogenic fragments.
AB  - The amyloid protein (A beta or beta A4) is the major constituent of amyloid
      plaques in the Alzheimer's disease brain. A beta is cleaved from the amyloid
      precursor protein (APP) by a mechanism which is poorly understood. Cell culture
      studies suggest that APP may be cleaved by secretases within the late Golgi
      compartment. Studies performed so far have mainly used exogenous APP and
      synthetic peptides as substrates. For this study, a Golgi and plasma membrane
      enriched fraction was isolated from rat brain and incubated at 37 degrees C at pH
      7.2 to study the degradation of endogenous APP. The breakdown of APP was
      accompanied by the concomitant generation of A beta-containing C-terminal
      fragments, in a time-dependent fashion. The metal ion chelators EDTA and 1,10
      phenanthroline inhibited this degradation. The inhibition by EDTA was reversed by
      50 microM Zn2+ but not by other metal ions. The protease activity was not
      inhibited by cysteine, serine or aspartic protease inhibitors nor was it
      inhibited by compounds which are inhibitors of known metalloendopeptidases and
      matrix metalloproteinases (cFP, phosphoramidon and TIMP-2). Our data suggest that
      a novel Zn(2+)-dependent metalloprotease activity associated with a Golgi and
      plasma membrane-enriched fraction can degrade endogenous APP to generate A beta
      containing C-terminal fragments. This protease may generate amyloidogenic
      fragments of APP which may serve as precursors for A beta.

PMID- 8993330
TI  - Energetic and kinetic contributions of contact residues of antibody D1.3 in the
      interaction with lysozyme.
AB  - Fully functional variable fragments (Fv) of D1.3, a mouse antibody directed
      against the hen egg lysozyme, were readily produced as hybrids (Fv-MalE) with the
      maltose-binding protein of Escherichia coli and purified independently of their
      antigen-binding properties. We used site-directed mutations of residues in the
      complementarity-determining regions (CDRs) of D1.3 as local conformational
      probes, and compared their effects on the binding of Fv and Fv-MalE to lysozyme.
      We found that the MalE moiety did not significantly interfere with the
      interaction between the antigen and the antibody Fv fragment. We then determined
      the contribution of several potential contact residues of D1.3 in the interaction
      with lysozyme, by assaying the effect of site-directed mutations on the kinetics
      of association and dissociation of the complex between Fv-MalE and immobilized
      lysozyme, using the BIAcore apparatus. While the k(on) values were virtually
      unaffected by the mutations, the k(off) values varied by more than three orders
      of magnitude. Both charged (aspartate and arginine) and aromatic (tyrosine and
      tryptophan) residues in the CDR3 regions of the heavy and light chains of D1.3,
      which form the center of its antigen-combining site, played a preponderant part
      in the binding of lysozyme. Our results also showed that indirect hydrogen bonds,
      bridged by water molecules, contributed significantly to the interaction between
      D1.3 and lysozyme, and that their energy could be estimated at 1 to 2 kcal.mol-1.

PMID- 8993331
TI  - Zn2+ promotes the self-association of human immunodeficiency virus type-1
      integrase in vitro.
AB  - It has been recently demonstrated that the Mg(2+)-dependent 3'-processing
      activity of purified human immunodeficiency virus type-1 (HIV-1) integrase is
      stimulated by the addition of exogenous Zn2+ [Lee, S. P., & Han, M. K. (1996)
      Biochemistry 35, 3837-3844]. This activation was hypothesized to result from
      integrase self-association. In this report, we examine the Zn2+ content of
      purified HIV-1 integrase by atomic absorption spectroscopy and by application of
      a thiol modification reagent, p-(hydroxymercuri)benzenesulfonate, with a
      metallochromic indicator, 4-(2-pyridylazo)resorcinol. We find that the Zn2+
      content of HIV-1 integrase varies from 0.1 to 0.92 equiv of Zn2+ per monomer
      depending on the conditions of protein purification. In vitro activity assays,
      time-resolved fluorescence emission anisotropy, and gel filtration
      chromatographic analyses all indicate that EDTA yields an apoprotein which is
      predominantly monomeric and less active with Mg2+. Further, sedimentation
      equilibrium studies reveal that reconstitution of the apoprotein with Zn2+
      results in a monomer-tetramer-octamer transition. These results suggest that Zn2+
      promotes a conformation with enhanced oligomerization and thereby stimulates
      Mg(2+)-dependent 3'-processing. This may also imply that multimers larger than
      dimers (tetramers and possibly octamers) are required for in vitro activity of
      integrase in the presence of Zn2+ and Mg2+. It should be noted, however, that the
      content of Zn2+ did not significantly affect the 3'-processing and strand
      transfer reactions with Mn2+ in vitro.

PMID- 8993332
TI  - Selective inhibition of the prothrombinase complex: factor Va alters
      macromolecular recognition of a tick anticoagulant peptide mutant by factor Xa.
AB  - The prothrombinase complex assembles through reversible interactions between the
      protease, factor Xa, the cofactor, factor Va, and acidic phospholipid membranes
      in the presence of calcium ions. Changes in macromolecular recognition by factor
      Xa which may result from its interaction with factor Va in the prothrombinase
      complex have been probed using a recombinant derivative of tick anticoagulant
      peptide where Arg3 has been replaced with Ala (R3A-TAP). In contrast to the wild
      type inhibitor, R3A-TAP was a weak competitive inhibitor of factor Xa (Ki = 794
      nM). The inhibition of the prothrombinase complex by R3A-TAP was characterized by
      slow, tight-binding kinetics with an increased affinity of approximately 4000
      fold (Ki* = 0.195 nM) relative to that of solution-phase factor Xa. Stopped-flow
      measurements using p-aminobenzamidine (PAB) demonstrated that the reaction
      between solution-phase factor Xa and R3A-TAP could be adequately described by a
      single reversible step with rate constants that were consistent with equilibrium
      binding measurements. The rate-limiting bimolecular combination of R3A-TAP and
      factor Xa was competitive with PAB binding of the protease. In contrast, the
      reaction of R3A-TAP with prothrombinase measured using PAB yielded biphasic
      stopped-flow traces, indicating a multistep pathway for the reaction of the
      inhibitor with the enzyme complex. The kinetic measurements were consistent with
      the initial formation of a ternary complex between R3A-TAP, prothrombinase, and
      PAB followed by two unimolecular steps which lead to PAB dissociation from the
      enzyme. In this case, prior occupation of the active site by PAB had no effect on
      the bimolecular reaction between R3A-TAP and prothrombinase. Thus, the
      interaction of factor Xa with factor Va on the membrane surface alters
      recognition of R3A-TAP by the protease, leading to changes in the thermodynamics
      as well as in the observed kinetic mechanism for the reaction. Therefore, a
      single amino acid substitution in TAP reveals large changes in macromolecular
      recognition by factor Xa as a consequence of its interaction with the cofactor
      within the prothrombinase complex.

PMID- 8993333
TI  - Slow alpha helix formation during folding of a membrane protein.
AB  - Very little is known about the folding of proteins within biological membranes. A
      "two-stage" model has been proposed on thermodynamic grounds for the folding of
      alpha helical, integral membrane proteins, the first stage of which involves
      formation of transmembrane alpha helices that are proposed to behave as
      autonomous folding domains. Here, we investigate alpha helix formation in
      bacteriorhodopsin and present a time-resolved circular dichroism study of the
      slow in vitro folding of this protein. We show that, although some of the
      protein's alpha helices form early, a significant part of the protein's secondary
      structure appears to form late in the folding process. Over 30 amino acids,
      equivalent to at least one of bacteriorhodopsin's seven transmembrane segments,
      slowly fold from disordered structures to alpha helices with an apparent rate
      constant of about 0.012 s-1 at pH 6 or 0.0077 s-1 at pH 8. This is a rate
      limiting step in protein folding, which is dependent on the pH and the
      composition of the lipid bilayer.

PMID- 8993334
TI  - Evidence that bilayer bending rigidity affects membrane protein folding.
AB  - The regeneration kinetics of the integral membrane protein bacteriorhodopsin have
      been investigated in a lipid-based refolding system. Previous studies on
      bacteriorhodopsin regeneration have involved detergent-based systems, and in
      particular mixed dimyristoylphosphatidylcholine (DMPC)/CHAPS micelles. Here, we
      show that the short chain lipid dihexanoylphosphatidylcholine (DHPC) can be
      substituted for the detergent CHAPS and that bacteriorhodopsin can be regenerated
      to high yield in mixed DMPC/DHPC micelles. Bacteriorhodopsin refolding kinetics
      are measured in the mixed DMPC/DHPC micelles. Rapid, stopped flow mixing is
      employed to initiate refolding of denatured bacterioopsin in SDS micelles with
      mixed DMPC/DHPC micelles and time-resolved fluorescence spectroscopy to follow
      changes in protein fluorescence during folding. Essentially identical refolding
      kinetics are observed for mixed DMPC/CHAPS and mixed DMPC/DHPC micelles. Only one
      second-order retinal/apoprotein reaction is identified, in which retinal binds to
      a partially folded apoprotein intermediate, and the free energy of this retinal
      binding reaction is found to be the same in both types of mixed micelles.
      Formation of the partially folded apoprotein intermediate is a rate-limiting step
      in protein folding and appears to be biexponential. Both apparent rate constants
      are found to be dependent on the relative proportion of DMPC present in the mixed
      DMPC/DHPC micelles as well as on the pH of the aqueous phase. Increasing the DMPC
      concentration should increase the bending rigidity of the amphiphilic bilayer,
      and this is found to slow the rate of formation of the partially folded
      apoprotein intermediate. Increasing the mole fraction of DMPC from 0.3 to 0.6
      slows the two apparent rate constants associated with formation of this
      intermediate from 0.29 and 0.031 to 0.11 and 0.013 s-1, respectively. Formation
      of the intermediate also slows with increasing pH, from 0.11 and 0.013 s-1 at pH
      6 to 0.033 and 0.0053 s-1 at pH 8. Since this pH change has no known effect on
      the phase behavior of lecithins, this is more likely to represent a direct effect
      on the protein itself. Thus, it appears to be possible to control the rate
      limiting process in bacterioopsin folding through both bilayer bending rigidity
      and pH.

PMID- 8993335
TI  - Very rapid, ionic strength-dependent association and folding of a heterodimeric
      leucine zipper.
AB  - Leucine zippers (coiled coils) are dimerization motifs found in several DNA
      binding transcription factors. A parallel leucine zipper composed of the acidic
      chain X1-EYQALEKEVAQLEAENX2-ALEKEVAQLEHEG-amide and the basic chain X1
      EYQALKKKVAQLKAKNX2ALKKKVAQLKHKG-amide was designed to study the kinetics of
      folding of a heterodimeric leucine zipper and to investigate the role of
      electrostatic attraction between oppositely charged peptide chains to the folding
      reaction. Each peptide alone did not form a leucine zipper at ionic strength (mu)
      < 1 M because of electrostatic repulsion between like charges in a homodimer.
      Therefore, the formation of the heterodimeric leucine zipper could be
      investigated by simple mixing of acidic and basic chains. To monitor folding, a
      fluorescent label was located either at the N-terminus (X1 = fluorescein-GGG, X2
      = Q) or in the center of the coiled coil (X1 = acetyl, X2 = W). Folding could be
      described by a simple two-state reaction involving the disordered monomers and
      the folded heterodimer. The same bimolecular rate constant (k(on)) was observed
      independent of the location of the fluorescent label, indicating that both
      fluorescence probes monitored the same reaction. Lowering of the ionic strength
      increased k(on) from 4 x 10(6) M-1 s-1 (mu = 525 mM) to about 5 x 10(7) M-1 s-1
      (mu = 74 mM). When extrapolated to mu = O, k(on) was approximately 10(9) M-1 s-1,
      which is near the diffusion limit. In contrast, the rate of dissociation depended
      very weakly on ionic strength; k(off) decreased only by about 2-fold when mu was
      lowered from 525 to 74 mM. Equilibrium association constants (Ka) of the
      heterodimeric zippers measured directly and calculated from kinetic constants (Ka
      = k(on)/k(off) were in good agreement. The observed two-state mechanism, the
      strong dependence on ionic strength of k(on) but not of k(off), and the nearly
      diffusion-limited association rate at very low ionic strength point to a folding
      pathway in which the formation of an electrostatically stabilized dimeric
      intermediate may be rate-limiting and the subsequent folding to the final dimer
      is very rapid and follows a "down-hill" free energy landscape. The small increase
      of k(off) at increasing ionic strength indicates a minor contribution of
      electrostatics to the stability of the folded leucine zipper.

PMID- 8993336
TI  - Binding mode of [ruthenium(II) (1,10-phenanthroline)2L]2+ with poly (dT*dA-dT)
      triplex. Ligand size effect on third-strand stabilization.
AB  - The binding of homochiral [Ru(II)(1,10-phenanthroline)2L]2+ complexes [where [L =
      1,10-phenanthroline (phen), dipyrido[3,2-a:2',3'-c]phenazine (DPPZ) or
      benzodipyrido[3,2-a:2',3'-c]phenazine (BDPPZ)] to poly(dT*dA-dT) triplex has been
      investigated by linear and circular dichroism and thermal denaturation. Analysis
      of the linear dichroism spectra indicates that the extended DPPZ and BDPPZ
      ligands lie approximately parallel to the base-pair and base-triplet planes
      consistent with intercalation which is also supported by strong hypochromism in
      the interligand absorption bands with either duplex or triplex. The spectral
      properties of any of the metal complex enantiomers were similar for binding to
      either duplex or triplex DNA, indicating that the third strand, which occupies
      the major groove of the template duplex, has little effect on the binding
      geometries and hence supports the hypothesis that the metal complexes all bind
      from the minor groove with the DPPZ and BDPPZ ligands intercalated but without
      intercalation in the case of [Ru(phen)3]2+. Third-strand stabilization depended
      on the nature of the third substituted phenanthroline chelate ligand but was not
      directly related to its size, with stabilizing power increasing in the order phen
      < BDPPZ < DPPZ. This observation further supports intercalation of the extended
      ligands from the minor groove of the triplex since the extended BDPPZ ligand that
      would protrude into the major groove of the template would have greater steric
      interference than DPPZ with the third DNA strand.

PMID- 8993337
TI  - Analysis of chicken progesterone receptor function and phosphorylation using an
      adenovirus-mediated procedure for high-efficiency DNA transfer.
AB  - The expression of heterologous DNA in mammalian cells is crucial to understanding
      physiological functions or determining biological properties of encoded proteins.
      However, expression for biological assay or at levels sufficient for recovery and
      subsequent physical analysis has been limited by the poor efficiency,
      variability, or cost of current DNA transfer methodologies. We have modified a
      DNA transfer procedure which exploits the capacity of replication-deficient
      adenovirus to infect a wide range of cell types, carrying with it transiently
      associated DNA. We have established conditions for achieving 80% transfection of
      CV1 cells and have used this procedure for DNA transfer into several mammalian
      cell lines and primary cell cultures. We have shown that biologically active
      avian progesterone receptor may be readily detected, both immunologically and
      functionally, using less than 1 ng of progesterone receptor-encoding plasmid DNA
      per 2 x 10(5) cells. We previously reported the identification of four
      phosphorylation sites in chicken progesterone receptor using oviduct tissue
      minces labeled with [32P]PO4 under nonequilibrium conditions. We now find, using
      adenovirus-mediated infection and equilibrium labeling conditions, that the same
      sites are phosphorylated in receptor expressed in CV1 cells and report that there
      are no additional major phosphorylation sites in chicken progesterone receptor.
      The ease, efficiency, sensitivity, and wide applicability of this DNA transfer
      method should simplify current efforts to study heterologous protein expression
      in mammalian cells.

PMID- 8993338
TI  - Molecular weight determination of lipoprotein(a) [Lp(a)] in solutions containing
      either NaBr or D2O: relevance to the number of apolipoprotein(a) subunits in
      Lp(a).
AB  - Molecular weight determination of low-density lipoprotein (LDL) is usually
      performed in solutions containing high concentrations of salt (up to 13.4 M NaBr)
      by sedimentation velocity and diffusion experiments, because it does not
      preferentially bind salt or water. Considering that lipoprotein(a) [Lp(a)] is
      structurally similar to LDL, differing only by the presence of Apo(a), the
      molecular weight, M, of Lp(a) has also been measured in solutions containing high
      concentrations of NaBr. We questioned the suitability of this practice by
      comparing the apparent molecular weight, Mapp, and partial volume, phi', of Lp(a)
      determined by sedimentation and flotation equilibrium in a three-component system
      containing NaBr with the analogous parameters, M and partial specific volume, v,
      determined in a two-component system containing D2O. LDL served as a control. In
      agreement with previous findings obtained with different methods, our results
      indicate no significant differences in M and v of four different LDL samples and
      apparently no significant preferential binding of solvent components. In
      contrast, values of Mapp and phi' of Lp(a) evaluated in NaBr are significantly
      greater than M and v. Preferential binding of solvent components appeared to be a
      function of Apo(a) mass or the number of kringle IV domains, as expressed by
      increasing percentage differences between the two sets of parameters, ranging
      from 4 to 13% in M and 0.2 to 0.5% in v of Lp(a) species having Apo(a) with 15-27
      kringle IV domains. Furthermore, our results indicate that the variable Apo(a)
      kringle IV domains are more involved in this process than the constant domain of
      Apo(a). These findings indicate that the Lp(a) molecular weight should be
      determined in D2O and that high concentrations of NaBr should be avoided as their
      use would lead to overestimated molecular weights and partial specific volumes.
      Application of this method to the question of how much Apo(a) is released upon
      the reduction of Lp(a) led to the conclusion that Lp(a) contains only one Apo(a)
      molecule.

PMID- 8993339
TI  - Pancreatic lipase structure-function relationships by domain exchange.
AB  - We designed chimeric mutants by exchanging the lid domains of the classical human
      pancreatic lipase (HPL) and the guinea pig pancreatic lipase related protein 2
      (GPLRP2). This latter enzyme possesses naturally a large deletion within the lid
      domain and is not activated by lipid/water interfaces. Furthermore, GPLRP2
      exhibits phospholipase A1 and lipase activities in the same order of magnitude,
      whereas HPL has no significant phospholipase activity and displays a clear
      interfacial activation. An HPL mutant [HPL(-lid)] with GPLRP2 mini-lid domain
      does not display interfacial activation. Its specific activity toward
      triglycerides is, however, dramatically reduced. A GPLRP2 mutant [GPLRP2(+lid)]
      with HPL full-length lid domain is not interfacially activated, and its lid
      domain probably exists under a permanent open conformation. Therefore, the
      phenomenon of interfacial activation in HPL is not only due to the presence of a
      full-length lid domain but also to other structural elements which probably allow
      the existence of stabilized closed and open conformations of the lid.
      GPLRP2(+lid) phospholipase activity is significantly reduced as compared to
      GPLRP2, whereas its lipase activity remains at the same level. Therefore, the lid
      domain plays a major role in substrate selectivity and can be considered as part
      of the active site. However, the presence of a full-length lid domain is not
      sufficient to explain the absence of phospholipase activity in HPL since HPL(
      lid) does not display any phospholipase activity. We also produced a chimeric
      GPLRP2 mutant in which the C-terminal domain was substituted by the HPL C
      terminal domain. The colipase effects, i.e., anchoring and stabilization of the
      lipase at the interface, are clearly observed with the chimera, whereas GPLRP2 is
      insensitive to colipase. The kinetic characterization of this chimera reveals for
      the first time that the interfacial stability of pancreatic lipases depends on
      the structure of the C-terminal domain.

PMID- 8993340
TI  - Backbone and side chain dynamics of lac repressor headpiece (1-56) and its
      complex with DNA.
AB  - The dynamics of the backbone and (some of) the side chains of lac headpiece (1
      56; lac HP56) have been studied for the free protein and for its complex with lac
      half-operator DNA by 15N T1 and T1p relaxation measurements combined with [1H
      15N] NOE experiments. For the structurally well-defined part of the free lac HP56
      (i.e., residues 3-49) a rigid backbone was found for residues in the three alpha
      helices and for the turn of the helix-turn-helix motif. The loop between helices
      II and III of lac headpiece, which was characterized by slight disorder in the
      structure calculations, shows increased mobility. The detected side chains are
      very mobile. These data are in full agreement with the rms deviations in the
      structural data of free lac HP56. When lac HP56 is complexed with DNA, several
      changes in mobility take place. The most remarkable change was found for the loop
      region between helices II and III: residue His-29 within this loop interacts with
      Thy-3 of the operator DNA. As a result this mobile loop adapts itself to the DNA
      and becomes more rigid. Moreover, most DNA-contacting side chains show a
      significant decrease in flexibility, although these side chains do not become as
      rigid as the backbone. These results suggest that the mobility of the regions
      within lac HP56 important for complexation, i.e., the loop and the DNA-contacting
      side chains, is essential for a good fit onto the counterparts of the target DNA.

PMID- 8993341
TI  - Induction of glyoxylate cycle expression in Caenorhabditis elegans: a fasting
      response throughout larval development.
AB  - The mRNA and the bifunctional protein for the two glyoxylate cycle (GC) enzymes,
      isocitrate lyase and malate synthase, are expressed in a tissue- and stage
      specific pattern in Caenorhabditis elegans. Since expression of the two enzymes
      for the carbon-conserving glyoxylate cycle is regulated by the availability of
      carbon sources in microorganisms, we have studied the bifunctional GCP gene
      expression under fasting conditions and in certain mutants of C. elegans in order
      to understand possible mechanisms regulating its expression during nematode
      development. The GCP mRNA and protein levels were elevated in early larvae which
      were never fed, a result consistent with previous enzyme activity measurements
      (Khan, F.R., & McFadden, B.A. (1982) Exp. Parasitol. 54, 48-54]. However, larvae
      of later stages also expressed higher levels of GCP mRNA and protein when they
      were shifted from normal to fasting growing conditions. The GCP expression
      appeared to be regulated primarily at the transcriptional level throughout
      development. Although the expression of both the GCP gene and lin-14 peaks at
      about the same time during development and are induced by fasting, the regulation
      of the GCP gene is independent of the heterochronic lin-14 control mechanism of
      postembryonic lineages, as demonstrated by the fact that there was no significant
      change of the GCP at both mRNA and protein levels in the heterochronic lin-4 (lf)
      and lin-14 (gf) mutants compared to the wild type.

PMID- 8993343
TI  - Cysteine-scanning mutagenesis of helix II and flanking hydrophilic domains in the
      lactose permease of Escherichia coli.
AB  - Using a functional lactose permease mutant devoid of Cys residues (C-less
      permease), each amino acid residue in putative transmembrane helix II and
      flanking hydrophilic loops (from Leu34 to Lys74) was replaced individually with
      Cys. Of the 41 single-Cys mutants, 28 accumulate lactose to > 70% of the steady
      state observed with C-less permease, and an additional 10 mutants exhibit lower
      but significant levels of accumulation (25-60% of C-less). His35-->Cys permease
      exhibits very low activity (ca. 20% of C-less), while Gly64-->Cys or Asp68-->Cys
      permease is unable to accumulate lactose. However, His35 can be replaced with Arg
      without effect on transport activity [Padan, E., Sarkar, H.K., et al. (1985)
      Proc. Natl. Acad. Sci. U.S.A. 82, 6765-6768]. In addition, even though mutant
      Gly64-->Cys or Glu68-->Cys is inactive both in the C-less background and in the
      wild-type, neither Gly64 [Jung, K., Jung, H., et al. (1995) Biochemistry 34, 1030
      1039] nor Glu68 [Jessen-Marshall, A.E., & Brooker, R.J. (1996) J. Biol. Chem.
      271, 1400-1404] is essential for active lactose transport. Immunoloblot analysis
      reveals that all of the mutants except His35-->Cys permease are inserted into the
      membrane at concentrations comparable to that of C-less permease. The transport
      activity of the single-Cys mutants is altered by N-ethylmaleimide (NEM) treatment
      in a highly specific manner. Most of the mutants are insensitive, but Cys
      replacements render the permease sensitive to NEM inactivation at positions that
      cluster in a manner indicating that they are on one face of an alpha-helix (Thr45
      ->Cys, Gly46-->Cys, Phe49-->Cys, Ser53-->Cys, Ser56-->Cys, Gln60-->Cys, and Ser67
      ->Cys). Interestingly, the same face contains positions where Cys substitution
      itself leads to low transport activity (Ile52-->Cys, Leu57-->Cys, Gln60-->Cys,
      and Gly64-->Cys). The results demonstrate that although no residue per se in this
      region of the permease is irreplaceable, the surface of one face of helix II is
      important for active lactose transport.

PMID- 8993342
TI  - Importance of the gamma-carboxyl group of glutamate-462 of the large alpha
      subunit for the catalytic function and the stability of the multienzyme complex
      of fatty acid oxidation from Escherichia coli.
AB  - His450 of the large alpha-subunit of the multienzyme complex of fatty acid
      oxidation from Escherichia coli was recently identified as an essential catalytic
      residue of L-3-hydroxyacyl-CoA dehydrogenase [He, X-Y., & Yang, S.-Y. (1996)
      Biochemistry 35, 9625-9630]. To explore the roles of acidic residues in the
      dehydrogenase catalysis, every conserved acidic residue in the dehydrogenase
      functional domain except for those in the NAD-binding motif was replaced with
      alanine. The resulting mutant complexes were overproduced and characterized.
      Their component enzymes other than the dehydrogenase were affected very slightly.
      Removal of the beta-carboxyl group of Asp524 and Asp542 caused only a 3- and 4
      fold, respectively, decrease in the catalytic efficiency of the dehydrogenase,
      thereby showing that their involvement in the dehydrogenase catalysis was
      limited. In contrast, the alpha/Glu462-->Ala mutant complex showed a greater than
      160-fold reduction in the kcat of the dehydrogenase in the forward direction
      without a significant change of the k(m) for the substrate. The catalytic
      properties of the alpha/Glu462-->Gln mutant complex were found to be similar to
      those of the alpha/Glu462-->Ala mutant complex except that the kcat of the
      dehydrogenase in the backward direction was about 4-fold lower and the Km for the
      substrate of the thiolase was 6-fold higher. It is concluded that the negative
      charge of the gamma-carboxyl group of Glu462, but not its ability to form a
      hydrogen bond, is critical for its interaction with His450, thereby assisting in
      the catalysis of the dehydrogenase. The pKa of His450 in the E.NADH binary
      complex was virtually unchanged by the replacement of Glu462 with Ala or Gln. It
      seems that the binding of substrate is necessary for forming a strong interaction
      between His450 and Glu462 with the result that the electroneutrality in the
      active site is maintained and the activation energy of the reaction is lowered.
      Additionally, the negative charge of Glu462 increases the thermostability of the
      multienzyme complex.

PMID- 8993344
TI  - The last two cytoplasmic loops in the lactose permease of Escherichia coli
      comprise a discontinuous epitope for a monoclonal antibody.
AB  - Monoclonal antibody (mAb) 4B11 binds to a conformational epitope in the lactose
      permease that is exposed on the cytoplasmic face of the membrane with a KD of 2.8
      x 10(-7) M. By studying binding of 4B11 to permease mutants containing six
      contiguous His residues in each cytoplasmic loop, inserted factor Xa protease
      sites, or a C-terminal deletion, the cytoplasmic loops between helices VIII and
      IX (loop VIII/IX) and between helices X and XI (loop X/XI) are shown to comprise
      the epitope. Subsequently, Cys-scanning mutagenesis in conjunction with thiol
      modification was carried out in order to identify specific residues involved in
      4B11 recognition. Glu342 and Arg344 in loop X/XI are primary determinants for
      4B11 binding, while Ile283 in loop VIII/IX and Phe334 and Lys335 in loop X/XI are
      secondary determinants. Consistently, binding of avidin to biotinylated single
      Cys replacements in loop VIII/IX or loop X/XI blocks 4B11 binding, but avidin
      binding to biotinylated Cys residues in other cytoplasmic loops or insertion of
      cytochrome b562 into cytoplasmic loop VI/VII has no significant effect. The
      studies demonstrate that the last two cytoplasmic loops in lactose permease
      comprise a discontinuous epitope for monoclonal antibody 4B11 and thereby provide
      independent evidence for the conclusion that helices VIII-XI are in close
      proximity.

PMID- 8993345
TI  - Structure and function of the Toxoplasma gondii vacuole.

PMID- 8993346
TI  - Analysis of the intracellular fate of Legionella pneumophila mutants.
AB  - L. pneumophila is a model organism for investigating the mechanisms by which
      intracellular pathogens acquire the metabolites needed for replication while
      evading the microbicidal mechanisms of the macrophage. We determined that
      intracellular L. pneumophila replicate in close association with the endoplasmic
      reticulum and suggest that L. pneumophila exploits the macrophage autophagy
      pathway to establish this specialized vacuole. To identify the bacterial factors
      required at this step as well as the factors important for other stages of the
      intracellular pathway, we isolated a collection of bacterial mutants that are
      defective for growth in macrophages. The ability of the mutant strains to evade
      fusion with the lysosomes and to establish replication vacuoles was examined by
      fluorescence microscopic localization of markers for the late endosomes (lgp
      120), lysosomes (Texas Red-ovalbumin), endoplasmic reticulum (BiP), and L.
      pneumophila. By this approach, we identified mutants with distinct intracellular
      fates; one type does not evade the endocytic pathway, another forms replication
      vacuoles less efficiently than does wild-type, and a third type forms replication
      vacuoles but replicates poorly. These mutants are likely to facilitate
      identification and characterization of the bacterial factors required by L.
      pneumophila to establish a protected niche for intracellular replication.

PMID- 8993347
TI  - Genetic and tissue culture systems for the study of bacterial pathogenesis.

PMID- 8993348
TI  - Enteropathogenic E. coli exploitation of host epithelial cells.
AB  - Enteropathogenic E. coli (EPEC) is a leading cause of neonatal diarrhea
      worldwide. These organisms adhere to the intestinal cell surface, causing
      rearrangement in the epithelial cell surface and underlying cytoskeleton,
      resulting in a structure termed an attaching/effacing (A/E) lesion. A/E lesion
      formation is thought necessary for EPEC-mediated disease. EPEC secretes several
      proteins that trigger signal transduction, intimate adherence, and cytoskeletal
      rearrangements in epithelial cells. Additionally, it produces intimin, an outer
      membrane product that mediates intimate adherence. Together these various
      bacterial molecules contribute to the intimate relationship that is formed by
      EPEC with host epithelial cells which results in A/E lesion formation and
      diarrhea.

PMID- 8993349
TI  - Differentially expressed genes of Mycobacterium tuberculosis.

PMID- 8993350
TI  - Molecular and cellular mechanisms of pneumococcal meningitis.

PMID- 8993351
TI  - Posttranslational modifications of meningococcal pili. Identification of a common
      trisaccharide substitution on variant pilins of strain C311.
AB  - Neisseria meningitidis pili are filamentous protein structures that are essential
      adhesins in capsulate bacteria. Pili of adhesion variants of meningococcal strain
      C311 contain glycosyl residues on pilin (PilE), their major structural subunit.
      Recent studies have shown that a novel O-linked trisaccharide substituent, not
      previously found as a constituent of glycoproteins, is present within a peptide
      spanning amino acid residues 50 to 73 of the PilE molecule. The structure was
      shown to be Gal beta 1-4 Gal alpha 1-3 diacetamidotrideoxyhexose which is
      directly attached to pilin. Pilins derived from galactose epimerase (galE)
      mutants lack the digalactosyl moiety, but retain the diacetamidotrideoxyhexose
      substitution. These studies confirm our previous observations that meningococcal
      pili are glycosylated and provide the first structural evidence for the presence
      of covalently linked carbohydrate on pili. We have identified a completely novel
      protein/carbohydrate linkage on a multimeric protein that is an essential
      virulence determinant in N. meningitidis.

PMID- 8993352
TI  - Genetic analysis of the Bordetella-host interaction.

PMID- 8993353
TI  - What happens in vivo to bacterial pathogens?

PMID- 8993354
TI  - Integrins: role in cell adhesion and communication.
AB  - Adhesive interactions are crucial for the integrity and function of all cells and
      tissues. As one of the major families of cell adhesion receptors, the integrins
      have been the focus of scientific interest for more than a decade. The resulting
      studies have tremendously enhanced the understanding of integrin-mediated
      adhesive interactions and have unveiled novel integrin functions in the
      cytoskeletal organization of microfilaments and in the activation of diverse
      signaling pathways. These functions are critically involved in the regulation of
      multiple processes, such as tissue development, inflammation, tumor cell growth
      and metastasis, and programmed cell death. The global view of integrin receptor
      biology has radically changed and has become much more subtle and elaborate. The
      enormous complexity of integrin function is determined by the heterodimeric
      formation of more than 20 functional integrin receptors, the cell type-specific
      distribution, the receptor activation state, the presence of different activation
      and deactivation signals, and the subsequent employment of distinct cytoskeletal
      and signaling complexes within a more dimensional network of time and space. This
      article summarizes the structural and functional properties of the integrin
      receptors and emphasizes some of the major achievements made in the past to
      enhance the understanding of integrin biology.

PMID- 8993355
TI  - Regulation of chemokine gene expression in human endothelial cells by
      proinflammatory cytokines and Borrelia burgdorferi.
AB  - Chemokines play a central role in the process of leukocyte recruitment to
      tissues. By their chemotactic activity they guide leukocytes to the site of
      infection/injury. Chemokines have been suggested to trigger firm adhesion of
      leukocytes to activated endothelial cells as well as the subsequent diapedesis.
      For these functions, chemokines produced by EC are particularly well suited. Our
      experiments with proinflammatory stimuli demonstrate that chemokines are induced
      in EC by a variety of stimuli including inflammatory cytokines and bacterial
      structures such as LPS and preparations of B. burgdorferi. The induction of
      chemokines by all of these agents occurs rapidly and does not require new protein
      synthesis. Two chemokines, MCP-1 and IL-8, respond to very low doses (0.1-1 U/ml)
      of proinflammatory cytokines which is important at the beginning of an immune
      response when soluble inflammatory mediators might still be limiting. The
      chemokines RANTES, IP-10, and mig show synergistic induction by low doses (1
      U/ml) of several inflammatory mediators, which again is important when only
      limiting amounts of inflammatory stimuli are present. The upregulation of six
      chemokine genes as well as genes encoding adhesion molecules in two cell types,
      EC and fibroblasts, by B. burgdorferi suggests that chemokines might play a
      central role in the regulation of spirochete-induced inflammatory responses and
      the subsequent immune responses. Recent evidence suggests that T cells with
      pathogenic potential contribute to chronic inflammation at the late stage of Lyme
      disease. Therefore, the use of therapeutic agents that block chemokine activity
      might be useful in treating chronic Lyme arthritis.

PMID- 8993356
TI  - Systemic and mucosal protective immunity to pneumococcal surface protein A.
AB  - To date our studies demonstrate that PspA is a highly immunogenic molecule in
      mice and that it can elicit immunity to otherwise fatal infections following iv,
      ip, in, and it challenge. Although the molecule is serologically variable, it is
      sufficiently cross-reactive so that immunization with a single PspA can protect
      against strains of highly diverse serotypes. It is anticipated that a vaccine
      composed of a mixture of carefully chosen PspA molecules will be able to elicit
      protective immunity to virtually all pneumococci. If this vaccine proved
      efficacious in man, it would provide a more simple and less costly means of
      immunizing against pneumococcal infection than using recombinant vaccines. This
      could be especially important in the developing world where the cost of
      successful vaccines must be no more than pennies per dose. If PspA is found to be
      less efficacious than capsular polysaccharides, it may be valuable as a protein
      component of a PS-protein conjugate vaccine. In this capacity, PspA might expand
      the breath of protection elicited by a vaccine composed of only a few
      polysaccharide-protein conjugates representing capsule types most commonly
      associated with infectious pneumococci.

PMID- 8993357
TI  - Heparan sulfate in immune responses.

PMID- 8993358
TI  - Antibody responses of rats and humans to flagella-less cells and OspA protein of
      Borrelia burgdorferi.

PMID- 8993359
TI  - Immunopathogenesis and immunoregulation in schistosomiasis. Distinct chronic
      pathologic syndromes in CBA/J mice.
AB  - Inbred CBA/J mice with chronic (20-week) Schistosoma mansoni infections
      demonstrate two distinct syndromes. Hypersplenomegaly syndrome (HSS),
      characterized by a massive spleen, liver fibrosis, ascites, and anemia, resembles
      hepatosplenic human schistosomiasis, complete with portal hypertension and
      shunting. Moderate splenomegaly (MSS) syndrome, with less severe pathology,
      parallels most chronic human infections. Phenotypic analyses of spleen cells for
      CD44, CD62L, CD45RB, Ia, and CD25 indicate that HSS mice have more activated and
      memory CD4+ T cells than do MSS mice. HSS animals also have more B cells that
      highly express B7-2. Anti-CD3 stimulated spleen cells from 8-week or chronically
      infected mice produce IL-4 and IL-10 in a manner that appears not to involve the
      CD28/B7-2 costimulation pathway. By contrast IFN-gamma production is augmented in
      the presence of anti-CD28 and decreased in the presence of anti-B7-2. Infected
      mice make very little IL-2 to anti-CD3, even with added anti-CD28. As cytokines
      affect resultant B-cell responses and HSS and MSS mice display distinctive
      isotypes, differential regulatory or anergy hypotheses may best explain MSS/HSS
      differences.

PMID- 8993360
TI  - Long-term antibody production is sustained by antibody-secreting cells in the
      bone marrow following acute viral infection.
AB  - Acute viral infection of humans induces virus-specific serum antibody production
      that often persists for decades. To better understand the nature of this long
      term antiviral antibody response, we studied antiviral antibody production of
      mice acutely infected with lymphocytic choriomeningitis virus (LCMV). Although
      this viral infection is resolved within 2 weeks, virus-specific serum antibody
      levels were maintained for > 300 days postinfection. The anatomic site of long
      term antibody production was identified using an ELISPOT assay to quantitate LCMV
      specific antibody-secreting cells (ASC). The initial antiviral ASC response in
      the spleen peaked at 8 days postinfection and then declined sharply, with less
      than 10% of the day 8 ASC population remaining after 60 days. Although no LCMV
      specific ASC were detected in the bone marrow at day 8, virus-specific ASC began
      accumulating in the bone marrow by 15 days postinfection. By day 60,
      approximately 10-fold more antiviral ASC were present in the bone marrow than in
      the spleen, and the bone marrow remained the major site of antibody production
      for > 10 months postinfection. To further characterize the LCMV-specific antibody
      response, the relative percentage of each IgG subclass (IgG1, IgG2a, IgG2b, and
      IgG3) was determined. IgG2a was the predominant IgG subclass produced during LCMV
      infection, and the IgG subclass profile of virus-specific ASC in the spleen and
      bone marrow matched the IgG subclass profile of virus-specific IgG in the serum.
      Following a secondary infection with LCMV, splenic ASC numbers increased rapidly
      with a peak at 5 days after secondary infection. This was followed by a sharp
      decline in ASC numbers by day 15. In contrast, virus-specific ASC numbers in bone
      marrow remained essentially unchanged during the acute phase of the secondary
      infection but increased approximately twofold at day 15, corresponding to a
      twofold increase in virus-specific serum antibody levels. These results indicate
      that following a primary viral infection or upon reexposure to a virus, the
      initial antibody response occurs in the spleen, but long-term antiviral antibody
      production is maintained in the bone marrow.

PMID- 8993361
TI  - Bacterial adherence and mucosal cytokine responses. Receptors and transmembrane
      signaling.
AB  - By attaching to cells or secreted mucosal components, microbes are thought to
      avoid elimination by the flow of secretions that constantly wash mucosal
      surfaces. The attached state enhances their ability to trap nutrients and allows
      the bacteria to multiply more efficiently than do unattached bacterial cells.
      Attachment is therefore regarded as an end result in itself, and emphasis has
      been placed on the role of adherence for colonization of mucosal surfaces.
      Specific adherence was shown to be essential for the tissue tropism that is to
      guide microbes to their respective sites of colonization/infection. Attachment is
      not only a mechanism of tissue targeting but also a first step in the
      pathogenesis of many infections. The attaching bacteria engage in a "cross-talk"
      with the host cells through the mutual exchange of signals and responses.
      Enteropathogenic E. coli induce attaching and effacing lesions (Finley et al.,
      this issue). Shigella and Listeria sp. invade the cells and cause actin
      polymerization (Sansonetti et al., this issue). This review describes the ability
      of bacteria to trigger mucosal inflammation through activation of cells in the
      mucosal lining. The results suggest that receptors for bacterial adhesins bind
      their ligands with a high degree of specificity and that ligand-receptor
      interactions trigger transmembrane signaling events that cause cell activation.
      Receptors for microbial ligands thus appear to fulfill also the same criteria as
      those used to define receptors for other classes of ligands such as hormones,
      growth factors, and cytokines.

PMID- 8993362
TI  - Development of an antipathology vaccine for schistosomiasis.
AB  - The data presented here clearly demonstrate that IL-12 can act as an adjuvant,
      suppressing both granuloma formation and fibrosis induced after natural
      schistosome infection. Recently, we showed that IL-12 can increase protective
      immunity provided by an attenuated larval schistosome vaccine as well. In both
      cases the vaccines appear to suppress in large part the parasite-induced Th2
      responses. Thus, the use of cytokines as adjuvants offers a rational approach for
      immunomodulation when the effector mechanism of a particular vaccine is known.
      Clearly, IL-12 has enormous potential for modulating the outcome of immunization
      and may have broad application in preventing a variety of different infectious
      diseases.

PMID- 8993363
TI  - Proteins expressed by DNA vaccines induce both local and systemic immune
      responses.

PMID- 8993364
TI  - Protective immunity to Listeria monocytogenes elicited by immunization with heat
      killed Listeria and IL-12. Potential mechanism of IL-12 adjuvanticity.
AB  - The results presented here demonstrate the striking potentiating effects of IL-12
      when it is combined with listerial immunogens. Although HKLM alone does not
      elicit strong T-cell responses, the results presented here demonstrate that the
      combination of HKLM and IL-12 elicited vigorous Listeria-specific Th1-type T-cell
      responses when administered intraperitoneally. The intensity of these responses,
      as well as the cytokine profiles of the Listeria-specific peritoneal T cells and
      macrophages, was remarkably similar to that of Listeria-infected/immune mice.
      These studies also revealed that typically nonimmunogenic forms of soluble
      listerial antigen preparations (cLLO, SLP) and LLO peptide homologs (M. A. Miller
      et al., manuscript in preparation) elicited intense Listeria-specific T-cell
      responses when administered with IL-12. In conjunction with the generation of
      specific T-cell responses following injection of IL-12 in combination with either
      killed Listeria or soluble listerial antigen preparations, macrophages from these
      mice expressed upregulated quantities of class II MHC and produced increased
      amounts of IL-12 following restimulation in vitro. Protection studies established
      that the Listeria-specific T-cell responses elicited by the HKLM + IL-12 mixture
      conferred protective immunity of mice to a lethal dose of viable L.
      monocytogenes. Studies designed to investigate the regulation of IL-12 production
      by peritoneal macrophages revealed that activated macrophages are particularly
      sensitive to bacterial products. However, nonviable or replication-incompetent
      bacteria or bacterial products injected alone were unable to influence the
      ability of macrophages to produce IL-12. The ability of activated macrophages to
      respond to HKLM was dramatically upregulated upon addition of IFN-gamma and
      markedly downregulated in the presence of the Th2 cytokines, IL-4 and IL-10. In
      light of what is known about the ability of IL-12 to induce IFN-gamma production
      by NK cells and gamma delta T cells, these results suggest that the exogenous
      addition of IL-12 may help initiate a cytokine cascade which enables the immune
      system to interact productively with an antigen that is typically nonimmunogenic
      when administered alone. These findings demonstrate that IL-12 may prove to be a
      powerful and broadly useful adjuvant component of particulate and soluble antigen
      based vaccines directed towards many types of intracellular pathogenic
      microorganisms. Studies aimed at determining the generality of these findings in
      other infectious disease models as well as experiments designed to further
      elucidate the mechanism(s) of IL-12 adjuvanticity are continuing.

PMID- 8993365
TI  - Endogenous vertebrate antibiotics. Defensins, protegrins, and other cysteine-rich
      antimicrobial peptides.
AB  - Although newly recognized, endogenous cystine-stabilized beta-sheet antimicrobial
      peptides have ancient origins. These peptides can arm circulating phagocytes and
      cells of the gastrointestinal, respiratory, and genitourinary tracts to resist
      invasion by bacteria, mycobacteria, fungi, and enveloped viruses. Defensins and
      protegrin-like peptides are likely to play a considerable role in innate immunity
      and may provide molecular templates that can be used to generate novel
      antibiotics for topical and systemic use.

PMID- 8993366
TI  - Identification of export proteins from Mycobacterium tuberculosis that interact
      with SecA.

PMID- 8993367
TI  - Fab' fragments of a mAb to a member of family 2 of trans-sialidases of
      Trypanosoma cruzi block trypanosome invasion of host cells and neutralize
      infection by passive immunization.

PMID- 8993369
TI  - Potent bactericidal activity towards gram-positive bacteria of mammalian group II
      phospholipase A2 mobilized in inflammatory fluids.

PMID- 8993368
TI  - Nitric oxide production by human alveolar macrophages in pulmonary disease.

PMID- 8993370
TI  - Structure-function studies with Neisseria gonorrhoeae Opa outer membrane proteins
      expressed in Escherichia coli.

PMID- 8993371
TI  - Model for pathogenesis of Mycobacterium avium.

PMID- 8993372
TI  - The Bcg gene (Nramp1) does not determine resistance of mice to virulent
      Mycobacterium tuberculosis.

PMID- 8993373
TI  - Both epidermal growth factor-like domains of the merozoite surface protein-1 from
      Plasmodium yoelii are required for protection from malaria.

PMID- 8993374
TI  - Role of passive humoral immunity in experimental mycetoma by Nocardia
      brasiliensis.

PMID- 8993375
TI  - A nontoxic chimeric cholera toxin analog.

PMID- 8993376
TI  - Bismuth-dimercaprol exposes surface components of Klebsiella pneumoniae
      camouflaged by the polysaccharide capsule.

PMID- 8993377
TI  - Use of salt to isolate Legionella pneumophila mutants unable to replicate in
      macrophages.

PMID- 8993378
TI  - Pathogenic mechanisms of Neisseria meningitidis.

PMID- 8993379
TI  - Identification of genes specifically expressed by Mycobacterium haemophilum in
      association with human epithelial cells.

PMID- 8993380
TI  - Identification of secreted proteins of Mycobacterium tuberculosis.

PMID- 8993381
TI  - Sequence studies on the COOH-terminal region of the merozoite surface protein-1
      in field samples of Plasmodium falciparum from diverse geographic areas.

PMID- 8993382
TI  - Prophylaxis with the immunomodulator PGG glucan enhances antibiotic efficacy in
      rats infected with antibiotic-resistant bacteria.
AB  - The emergence of multiple antibiotic-resistant microorganisms has led to a search
      for alternatives to traditional therapeutic regimens. PGG glucan is a soluble
      beta-glucan immunomodulator that selectively enhances the microbicidal activities
      of neutrophils and macrophages without stimulating proinflammatory cytokine
      production. In the present studies, we examined the ability of PGG glucan to act
      in concert with antibiotics to decrease mortality in a rat model of
      intraabdominal sepsis using antibiotic-resistant bacteria as infectious inocula.
      Results of these studies demonstrated that prophylaxis with PGG glucan in
      combination with antibiotics provided enhanced protection against lethal
      challenge with Esherichia coli or Staphylococcus aureus as compared with the use
      of antibiotics alone.

PMID- 8993383
TI  - Cytoplasmic proteins involved in thyroid hormone response also bind Neisseria
      gonorrhoeae Opa outer membrane proteins.

PMID- 8993384
TI  - Analysis of the role of invasin during Yersinia pseudotuberculosis infection of
      mice.

PMID- 8993385
TI  - In vitro models to study attachment and invasion of Helicobacter pylori.

PMID- 8993386
TI  - Impact of in vitro fatty acid uptake on nitric oxide production and antilisterial
      activity of WEHI-3 cells.

PMID- 8993387
TI  - Pathogenesis and immune responses in shigellosis.

PMID- 8993388
TI  - Endoprotease regulation of miniglucagon production.

PMID- 8993389
TI  - The biosynthetic processing and secretion of endogenous carboxypeptidase H in
      mouse pituitary cells.

PMID- 8993390
TI  - Synthesis and biochemical characterization of proglucagon-related peptides.

PMID- 8993391
TI  - Glucagon and its receptor in various tissues.

PMID- 8993392
TI  - PACAP/VIP receptors in pancreatic beta-cells: their roles in insulin secretion.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide
      belonging to the vasoactive intestinal polypeptide (VIP)/glucagon/secretin
      family. We have isolated a third PACAP receptor subtype, designated PACAPR-3, by
      molecular cloning. The cDNA encoding PACAPR-3 has been isolated from a mouse
      insulin-secreting beta-cell line MIN6 cDNA library. Mouse PACAPR-3 is a protein
      of 437 amino acids that has 50% and 51% identity with rat PACAP type I and type
      II receptors, respectively. We have expressed PACAPR-3 in mammalian cells and
      Xenopus oocytes. PACAPR-3 binds to VIP as well as PACAP-38 and -27, with a
      slightly higher affinity for PACAP-38, and is positively coupled to adenylate
      cyclase. PACAP-38, -27, and VIP evoked Ca2+ activated-Cl- currents in Xenopus
      oocytes. RNA blotting studies reveal that PACAPR-3 mRNA is expressed widely in
      tissues and cell lines, including pancreatic islets, insulin-secreting cell lines
      (MIN6, HIT-T15, and RINm5F), lung, brain, stomach, colon, and heart. Furthermore,
      insulin secretion from the MIN6 cells is stimulated significantly by PACAP-38 and
      VIP. The possible mechanisms of insulin secretion by PACAP and VIP are also
      discussed.

PMID- 8993393
TI  - Differential signaling and immediate-early gene activation by four splice
      variants of the human pituitary adenylate cyclase-activating polypeptide receptor
      (hPACAP-R).
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide
      belonging to the VIP/secretin/glucagon family, is present in the hypothalamus,
      anterior pituitary, and adrenal gland where it regulates hormone release, in the
      GI tract where it modulates motility, and in human tumoral cell lines where it
      shows a growth-promoting effect. It is now appreciated that alternative splicing
      of two exons of the rat PACAP-R gene generate four major rPACAP-R splice variants
      that are differentially expressed in tissues and variably coupled to
      intracellular second messengers. Because of the potential implications of these
      findings in human physiology, we cloned the hPACAP-R gene. Similar to the rat,
      two exons (SV-1 and SV-2) are alternatively spliced to account for four major
      hPACAP-R receptor splice variants. These splice variants (hPACAP-R-null, hPACAP-R
      SV1, hPACAP-R-SV2, hPACAP-R-SV-3) were cloned from a human frontal cortex cDNA
      library, stably transfected in NIH/ 3T3 cells and each characterized for ligand
      affinity, stimulation of adenylate cyclase (AC) and phospholipase C (PLC), and
      ligand-induced expression of the proto-oncogenes, c-fos, and c-myc. Stably
      transfected NIH/3T3 cells expressing similar numbers of receptors of the four
      splice variants showed nearly identical responses for ligand affinity and potency
      for P-38- and P-27-stimulated increases in cAMP and total inositol phosphates.
      However, each receptor splice variant differed in their ligand-stimulated
      efficacy for total inositol phosphate stimulation. The hPACAP-R-SV2 showed the
      greatest efficacy for stimulating phospholipase C that was approximately seven
      fold greater than the hPACAP-R-SV1, twofold greater than the hPACAP-R-Null, and
      1.5-fold greater than the hPACAP-R-SV-3 splice variants. To determine whether the
      splice variants also differ in their ability to stimulate immediate early gene
      expression, c-fos and c-myc transcripts were assayed by Northern blot and
      quantified by densitometry. PACAP-38 increased c-fos and c-myc expression for all
      four of the receptor splice variants that paralleled the efficacy for PLC
      stimulation, with the the SV-2 splice variant showing the greatest stimulation.
      These results show that the hPACAP-R-SV2 exhibits enhanced efficacy for coupling
      to both PLC and activation of the protooncogenes, c-fos and c-myc suggesting a
      novel and potentially important mechanism for differentially activating signal
      transduction pathways that influence cellular growth and differentiation.

PMID- 8993394
TI  - Genetic dissection of signal transduction mechanisms underlying PACAP-like
      neuropeptide transmission in Drosophila: synergy of cAMP and Ras/Raf pathways.

PMID- 8993396
TI  - Receptors for VIP, PACAP, secretin, GRF, glucagon, GLP-1, and other members of
      their new family of G protein-linked receptors: structure-function relationship
      with special reference to the human VIP-1 receptor.

PMID- 8993395
TI  - Signal transduction of PACAP and GLP-1 in pancreatic beta cells.
AB  - PACAP and GLP-1 depolarize pancreatic beta cells and stimulate insulin secretion
      in the presence of glucose. Depolarization occurs through at least two distinct
      mechanisms: (1) closure of ATP-sensitive K+ channels, and (2) activation of
      nonselective cation channels (NSCCs). Under physiological conditions the NSCCs
      carry a predominantly Na(+)-dependent current. The current may also have a Ca2+
      component, but this remains to be determined. Acting together, these two
      signaling systems reinforce each other and serve to promote membrane
      depolarization, a rise of [Ca2+]i, and exocytosis of insulin-containing secretory
      granules. The NSCCs in beta cells are dually regulated by intracellular cAMP and
      [Ca2+]i. In view of this dual regulation, it appears likely that NSCC channel
      activation results from signaling events occurring not only at the plasma
      membrane (gating of channels by cAMP; protein kinase A-mediated phosphorylation
      of channels) but also at intracellular sites (mobilization of calcium stores by
      an as yet to be determined process). It is noteworthy that activation of NSCCs
      has also been reported following stimulation of beta-cells with maitotoxin, or
      after depletion of intracellular Ca2+ stores. Therefore, the possibility arises
      that PACAP, GLP-1, and maitotoxin all act on the same types of ion channels in
      these cells, and that these channels are sensitive to alterations in the content
      of intracellular calcium. FIGURE 6 summarizes our current knowledge concerning
      the properties of the PACAP and GLP-1 signaling systems as they pertain to the
      regulation of NSCCs and intracellular calcium homeostasis in the beta cell. Given
      that PACAP and GLP-1 are proven to be exceptionally potent insulin secretagogues,
      it is of considerable interest to determine their usefulness as blood glucose
      lowering agents. Initial evaluations of the therapeutic effectiveness of GLP-1
      indicate a role for this peptide in the treatment of NIDDM, and also possibly
      insulin-dependent diabetes mellitus (IDDM). A very attractive feature of such a
      strategy is the demonstrated lack of hypoglycemic side effects attendant to
      administration of GLP-1 to diabetic subjects. These observations reinforce the
      notion that peptides of the PACAP/glucagon/VIP family represent important
      pharmacological tools for use in experimental therapeutics.

PMID- 8993398
TI  - Pancreatic beta-cell receptors and G proteins coupled to adenylyl cyclase.
AB  - Glucagon and tGLP-1 receptors can be either coexpressed or selectively expressed
      in beta-cell models. Our results indicate that both these peptides can regulate
      insulin secretion from beta-cells through their own specific receptors. The
      finding of a selective expression of G proteins in insulin and glucagon cells
      indicates a clear difference in their transduction pathways. A key role of the G
      alpha s family in beta-cell function is further supported by its conserved cell
      distribution between different species. In conclusion, one could postulate that
      in the human beta-cells, tGLP-1 and glucagon receptors could mediate their action
      through different G protein alpha-subunits of the G alpha s family.

PMID- 8993397
TI  - Functional interaction between gonadotropin-releasing hormone and PACAP in
      gonadotropes and alpha T3-1 cells.
AB  - Gonadotropes, like other cells, receive informational input from multiple
      receptor types, acting through multiple intracellular signaling pathways, and are
      therefore faced with the task of integrating this input in order to respond
      appropriately to their environment. In recent years an increasing number of
      examples of functional interactions occurring between the PIC and adenylyl
      cyclase signaling pathways in gonadotropes have been described, and the discovery
      that these cells are targets for PACAP has provided a physiological context for
      earlier work on gonadotrope regulation by cyclic AMP. The development of the
      alpha T3-1 cell line has greatly facilitated investigation of the interaction
      between these signaling systems. In these cells we have obtained no evidence for
      interaction between the GnRH and PACAP receptor-effector systems at the level of
      receptor occupancy or expression, but these systems clearly do have reciprocal
      modulatory effects on second messenger generation and/or mobilization. We are now
      faced with the challenge of determining the physiological and/or
      pathophysiological relevance of such interactions.

PMID- 8993399
TI  - The control of fluid-secreting epithelia by VIP.

PMID- 8993400
TI  - Structural simplification of potent growth hormone-releasing hormone analogs:
      implications for other members of the VIP/GHRH/PACAP family.

PMID- 8993401
TI  - Development of VIP agonists and antagonists with tissue and receptor specificity:
      effects on behavioral maturation, sexual function, and the biologic clock.

PMID- 8993402
TI  - Speculations on the mechanism of hormone-receptor interactions of the
      secretin/glucagon family of polypeptide hormones derived from computational
      structural studies.

PMID- 8993403
TI  - The growth-hormone-releasing hormone receptor: signal transduction, gene
      expression, and physiological function in growth regulation.
AB  - We now summarize key issues that we have investigated and highlight additional
      areas that need to be addressed. We are interested in two basic aspects of the
      GHRH pathway, those occurring in the brain, involving the synthesis of GHRH, and
      those occurring in the pituitary, involving signaling by GHRH. We have a long
      term interest in the activity and regulation of the hypothalamic neurosecretory
      cells that synthesize GHRH. With respect to human disease, it is interesting
      that, despite the primal role played by GHRH in growth-hormone secretion, no
      mutations in the GHRH gene have yet been identified in association with growth
      disorders. Focusing on the downstream signaling components of the GHRH pathway,
      we now know quite a lot about the structure of the GHRH receptor and about some
      aspects of the signal transduction pathways that mediate the actions of GHRH.
      With respect to human disease, we have found that in an animal model, the little
      mouse, a mutation of the GHRH receptor results in growth-hormone deficiency and a
      dwarf phenotype, and there are ongoing attempts in several laboratories to try to
      identify similar inactivating mutations in the GHRH receptor in patients with
      isolated growth-hormone deficiency. Conversely, there is also substantial
      interest in whether activating mutations in this receptor might be identified in
      patients with growth-hormone-secreting pituitary tumors. We are also interested
      in whether there are additional receptors that might mediate some of the
      extrapituitary actions of GHRH. Finally, a major direction we are taking in the
      laboratory at the present time is toward understanding the developmental,
      hormonal, and tissue-specific regulation of the GHRH receptor gene.

PMID- 8993405
TI  - Short- and long-term regulation of tyrosine hydroxylase in chromaffin cells by
      VIP and PACAP.
AB  - Whereas cholinergic neurotransmitters are responsible for the release of a
      substantial portion of the CAs released from rat chromaffin cells by activation
      of the splanchinc nerves, the present data suggest that noncholinergic
      neurotransmission appears to play a more substantial role in the short- and long
      term homeostatic regulation of TH activity, which serves to maintain the stores
      of CAs for subsequent release. In addition, studies using the PKA-deficient PC12
      cells provided the first direct evidence that PKA actually mediates the
      phosphorylation of Ser40 in situ.

PMID- 8993406
TI  - Enhancement of glucose-induced insulin secretion in transgenic mice
      overexpressing human VIP gene in pancreatic beta cells.
AB  - Using transgenic mice technology, it has now become possible to test directly
      whether VIP and PHM-27 can enhance glucose-induced insulin secretion and reduce
      blood glucose in vivo. By microinjecting the entire human VIP gene ligated to the
      rat insulin II promoter, we have established a mouse model that overproduces VIP
      and PHM-27 in pancreatic beta cells. VIP was secreted from transgenic islets in a
      glucose-dependent manner. Analyses of these VIP-transgenic mice indicated that
      the transgene efficiently enhances glucose-induced insulin secretion and
      significantly reduces blood glucose as compared with control mice. The transgene
      also ameliorated glucose intolerance of 70% depancreatized mice. The present
      results suggest that somatic cell gene therapy directed to diabetic islets by
      human VIP/PHM-27 gene introduction may provide a means to improve the secretory
      function of the diabetic islets.

PMID- 8993404
TI  - Pituitary adenylate cyclase-activating polypeptides, PACAP-38 and PACAP-27,
      regulation of sympathetic neuron catecholamine, and neuropeptide Y expression
      through activation of type I PACAP/VIP receptor isoforms.
AB  - The current studies have implicated a prominent role for PACAP peptides in
      modulating the physiological function of cells derived from the sympathoadrenal
      lineage. Compared to VIP, both PACAP-27 and PACAP-38 demonstrated potent,
      efficacious, and sustained stimulatory effects on sympathetic neuronal NPY and
      catecholamine production. The differential effects of PACAP peptides on SCG NPY
      and catecholamine content and secretion coincided with previous studies that
      activated directly the sympathetic intracellular cyclic AMP-protein kinase A
      signaling pathway. These effects appear to be mediated primarily by PACAP1
      receptor splice variants coupled to both adenylyl cyclase and phospholipase C in
      SCG neurons. The actions of PACAP peptides in the SCG shared many parallels with
      adrenal medullary chromaffin cells, suggesting diverse roles for the PACAP
      peptidergic system in sympathoadrenal cell development and function. Rather than
      solutions, these results pose additional questions for the future. What are the
      endogenous sources of PACAP that regulate sympathetic and adrenal function? Do
      PACAP peptides, like VIP, have dual roles and also act as sympathetic
      postganglionic neuromodulators? Are VIP/PACAP receptors expressed during SCG
      development? What regulates sympathetic PACAP1 receptor isoform expression and
      how are they differentially coupled to neuronal intracellular signaling cascades?
      What defines the tissue-specific responses to PACAP-27 and PACAP-38? While many
      of these questions are not easily approached, future studies of these issues will
      certainly illuminate the function of PACAP and PACAP receptors in the nervous and
      endocrine systems.

PMID- 8993407
TI  - Region-specific regulation of neurogenesis by VIP and PACAP: direct and indirect
      modes of action.

PMID- 8993408
TI  - VIP regulation of embryonic growth.
AB  - Vasoactive intestinal peptide (VIP) plays a regulatory role in the growth of
      early postimplantation rodent embryos through its action on receptors localized
      to the central nervous system (CNS). However, the origin of the VIP influencing
      embryonic growth is unknown. VIP binding sites have been found prenatally;
      however, VIP mRNA was not detected in the rat CNS before birth and has been
      detected in peripheral organs only during the final third of gestation. Recent
      studies have revealed that VIP receptors were limited to the CNS in the embryonic
      day 11 (E11) rat embryo/trophoblast, which, in addition, had almost four times
      the VIP concentration of the E17 fetus. However, neither in situ hybridization or
      reverse transcriptase-polymerase chain reaction methods detected VIP mRNA in the
      E11 rat embryo or embryonic membranes. Rat maternal serum revealed a peak in VIP
      concentration at days E10-E12 of pregnancy, with VIP levels 6- to 10-fold higher
      than later during pregnancy. Radiolabeled VIP, administered intravenously to
      pregnant female mice, was found in the E10 embryo. These results suggest that VIP
      produced by extraembryonic tissues may regulate embryonic growth during the early
      postimplantation stage of development in the rodent.

PMID- 8993409
TI  - Transport of pituitary adenylate cyclase-activating polypeptide across the blood
      brain barrier and the prevention of ischemia-induced death of hippocampal
      neurons.
AB  - PACAP is a member of the secretin/glucagon/VIP family of peptides and
      demonstrates neurotrophic and neuroprotective effects at very low concentrations.
      We have previously shown that PACAP crosses the BBB to a modest degree by way of
      a saturable transport system. PACAP is transported across the BBB as an intact
      peptide to enter the parenchymal space of the brain. We tested the possibility
      that this modest rate of transport would be sufficient to produce the low levels
      of PACAP needed in the brain to exert a neuroprotective effect against ischemia.
      We found that PACAP given intravenously could indeed prevent the death of CA1
      hippocampal neurons, even if the administration of PACAP was delayed for 24 h
      after the ischemic event. We suggest that iv PACAP could be neuroprotective after
      stroke, cardiac arrest, and hypotensive episodes.

PMID- 8993410
TI  - Vasoactive intestinal peptide releases interleukin-1 from astrocytes.

PMID- 8993411
TI  - VIP and PACAP receptor-mediated actions on cell proliferation and survival.

PMID- 8993412
TI  - Ontogeny of PACAP and PACAP receptors in the rat brain: role of PACAP in the
      cerebellum during development.

PMID- 8993413
TI  - PACAP/VIP receptor subtypes, signal transducers, and effectors in pituitary
      cells.
AB  - Rat anterior pituitary tissue expresses mRNA for PVR1 and PVR3, as well as a low
      level of PVR2. The PVR1 appears to be highly expressed in gonadotroph-like cells,
      while somatotroph-like cells apparently express the PVR3. We have recently
      demonstrated the expression of mRNA for both PVR2 and PVR3 in corticotroph-like
      AtT20 cells (FIG.3). If normal corticotrophs express the same mRNA as AtT20
      cells, this may partly explain the low levels of PVR2 seen in normal pituitary
      tissue. Significant levels of at least two PVR1 splice variants mRNAs (PVR1s and
      PVR1hop) were expressed in clonal gonadotroph-like alpha T3-1 cells and normal
      rat anterior pituitary tissue. However, these splice variants are reported to
      have almost identical pharmacological characteristics in terms of binding, and
      the activation of AC and PLC. Further experiments are necessary to determine the
      functional consequences of differential splice variant expression in such cells.
      Interestingly, all three pituitary-cell lines studied expressed mRNA for the PVR3
      (FIG.3), whereas earlier binding studies demonstrate a predominance of PACAP
      preferring binding sites on normal anterior pituitary-cell membranes. In
      addition, it is clear that the different PVR subtypes can couple to different
      intracellular messenger systems. Thus it will be important to determine the
      expression of the different PVR subtypes in normal anterior pituitary-cell types
      if we are to begin to understand the regulation of pituitary-cell regulation by
      PACAP. Such questions form the basis of some of the ongoing studies in our
      laboratory.

PMID- 8993415
TI  - Effects of GnRH and PACAP on gonadotropin secretion and subunit messenger RNAs.

PMID- 8993414
TI  - Current status of PACAP as a regulator of insulin secretion in pancreatic islets.
AB  - PACAP-27 and PACAP-38 as low as 10(-13) M stimulate insulin release from rat
      islets in a glucose-dependent manner. PACAP also glucose dependently increases
      cAMP and [Ca2+]i in rat islet beta cells. The [Ca2+]i and insulin secretory
      responses to PACAP exhibit a similar concentration-response relationship,
      exhibiting a peak at 10(-13) M. When the [Ca2+]i response is abolished by
      nitrendipine, a blocker of L-type Ca2+ channels, the insulin response is also
      inhibited. Insulinotropic peptides glucagon, GLP-1, and VIP also increase [Ca2+]i
      in beta cells, but only in the nanomolar concentration range. PACAP is 4 logs
      more potent that VIP, a peptide that exhibits 68% amino acid homology and shares
      the type II PACAP receptor with PACAP. Immunoreactivity for the type I PACAP
      receptor is demonstrated in rat islets. Furthermore, PACAP immunoreactivity is
      demonstrated in nerve fibers and islets in rat pancreas. Based on these findings,
      we can draw the following conclusions: (1) PACAP is localized in pancreatic nerve
      fibers and islets; (2) PACAP in the subpicomolar range stimulates insulin release
      from islets; (3) the stimulation of insulin release is mediated by the cAMP
      dependent increase in [Ca2+]i in beta cells; (4) all the PACAP effects are
      glucose-dependent; (5) PACAP is the most potent insulinotropic hormone known, and
      (6) the type I PACAP receptor appears to mediate the action of PACAP in the
      subpicomolar range. Finally, we hypothesize that PACAP is a pancreatic peptide of
      both neural and islet origin and functions as an intrinsic potentiator of glucose
      induced insulin secretion in pancreatic islets (FIG 6).

PMID- 8993416
TI  - Interplay of VIP and nitric oxide in the regulation of neuromuscular function in
      the gut.

PMID- 8993417
TI  - Role of PACAP in the regulation of gastrointestinal motility.

PMID- 8993418
TI  - Vasoactive intestinal peptide and nitric oxide: divergent roles in relation to
      tissue injury.

PMID- 8993419
TI  - VIP inhibits the proliferation of small-cell and nonsmall-cell lung carcinoma.

PMID- 8993420
TI  - Role of PACAP in the female reproductive organs.

PMID- 8993421
TI  - Pituitary adenylate cyclase-activating peptide in sensory and autonomic ganglia:
      localization and regulation.

PMID- 8993422
TI  - Analysis of cardiovascular responses to PACAP-27, PACAP-38, and vasoactive
      intestinal polypeptide.
AB  - Responses to pituitary adenylate cyclase polypeptide (PACAP)-27, PACAP-38, and
      vasoactive intestinal peptide (VIP) were compared in the peripheral and pulmonary
      vascular beds of the cat and in the isolated perfused neonatal pig heart.
      Intravenous injections of PACAP-27 and PACAP-38 produced biphasic changes in
      systemic arterial pressure whereas iv injections of VIP caused only decreases in
      arterial pressure. When blood flow to the hind limb and mesenteric vascular beds
      was maintained constant, PACAP-27 and PACAP-38 caused dose-related biphasic
      changes in perfusion pressure, whereas VIP only decreased perfusion pressure.
      PACAP-27 was approximately threefold more potent than PACAP-38, and the pressor
      component of the biphasic response was blocked by alpha-adrenergic antagonists
      and adrenalectomy. PACAP-27, PACAP-38, and VIP produced decreases in pulmonary
      vascular resistance, and all three peptides had significant vasodilator activity
      in the isolated perfused neonatal pig heart. Although all three peptides
      decreased coronary vascular resistance, only PACAP-27 and PACAP-38 increased left
      ventricular contractility, with PACAP-27 approaching isoproterenol in potency.
      The results of these experiments show that PACAP-27, PACAP-38, and VIP have
      significant effects on vasomotor tone that depend on the vascular bed studied and
      the contribution of adrenal catecholamines.

PMID- 8993423
TI  - Basic aspects of vasorelaxant and bronchodilating peptides in clinical use:
      urodilatin (INN: Ularitide), VIP, and PACAP.

PMID- 8993424
TI  - Pituitary adenylate cyclase-activating polypeptide induces gene expression of the
      catecholamine synthesizing enzymes, tyrosine hydroxylase, and dopamine beta
      hydroxylase in cultured porcine adrenal medullary chromaffin cells.

PMID- 8993425
TI  - Activation of pituitary adenylate cyclase-activating polypeptide receptors
      prevents apoptotic cell death in cultured cerebellar granule cells.

PMID- 8993426
TI  - Stimulatory effect of PACAP on neuronal cell survival.

PMID- 8993427
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neurotrophic
      factor for cultured rat cortical neurons.

PMID- 8993428
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a regulator of
      astrocytes: PACAP stimulates proliferation and production of interleukin 6 (IL
      6), but not nerve growth factor (NGF), in cultured rat astrocyte.

PMID- 8993429
TI  - Protection of rat retina from ischemia-reperfusion injury by vasoactive
      intestinal peptide (VIP): the effect of VIP on lipid peroxidation and antioxidant
      enzyme activity of retina and choroid.

PMID- 8993430
TI  - Structure-activity studies on VIP: IV. The synthetic agonist helodermin-fragment
      (1-28)-amide is a potent VIP-agonist with prolonged duration of tracheal relaxant
      activity.

PMID- 8993431
TI  - Structure-activity relationship studies of PACAP-27 and VIP analogues.

PMID- 8993433
TI  - Vasoactive intestinal peptide activates both Gs and Gi in lung.

PMID- 8993432
TI  - Effects of PACAP-VIP hybrid peptides on gastric blood flow in conscious dogs.

PMID- 8993434
TI  - PACAP 1-27 and 1-38 in the porcine pancreas: occurrence, localization, and
      effects.

PMID- 8993436
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and insulin secretion:
      effects and mechanisms.

PMID- 8993435
TI  - A novel PACAP 1-27 analogue causes sustained smooth muscle relaxation in guinea
      pig trachea.

PMID- 8993437
TI  - Subcellular localization of G-protein alpha subunits in adult rat islets.

PMID- 8993438
TI  - Ocular expression of type-I pituitary adenylate cyclase-activating polypeptide
      (PACAP) receptors.

PMID- 8993439
TI  - Mutagenesis of N-glycosylation sites in the human VIP 1 receptor.

PMID- 8993440
TI  - Evidence of G-protein alpha s and alpha olf subunits in developing human
      pancreas.

PMID- 8993441
TI  - Establishment of a CHO cell clone stably expressing the recombinant human VIP-1
      receptor.

PMID- 8993442
TI  - Chimaeric VIP2/PACAP receptors reveal that agonist pharmacology but not signal
      transduction is determined by extracellular domain 1.

PMID- 8993443
TI  - Phospholipase C activation by VIP1 and VIP2 receptors expressed in COS 7 cells
      involves a pertussis toxin-sensitive mechanism.

PMID- 8993444
TI  - Role of cysteine residues in the N-terminal extracellular domain of the human VIP
      1 receptor for ligand binding. A site-directed mutagenesis study.

PMID- 8993445
TI  - Purification of recombinant human pituitary adenylate cyclase-activating
      polypeptide receptor expressed in Sf9 insect cells.

PMID- 8993446
TI  - PACAP and type I PACAP receptors in the pineal gland.

PMID- 8993447
TI  - Characterization of cloned somatostatin receptor subtypes. Localization of rat
      SSTRs in gastrointestinal tissues, SSTR1 gene promoter studies, and mutational
      analyses of SSTR3.

PMID- 8993449
TI  - Astrocytes are one of the main target cells for pituitary adenylate cyclase
      activating polypeptide in the central nervous system. Astrocytes are very
      heterogeneous regarding both basal movement of intracellular free calcium
      ([Ca2+]i) and the [Ca2+]i response to PACAP at a single cell level.

PMID- 8993448
TI  - Mechanisms of action of VIP and PACAP in the stimulation of insulin release.
AB  - VIP and PACAP stimulate insulin release by interaction with the VIP-2/PACAP-3
      receptor on the beta cell. Activation of the receptor results in Gs-mediated
      stimulation of adenylyl cyclase and increased cellular cyclic AMP levels.
      Increased cyclic AMP results in a small and transient increase in [Ca2+]i, which
      is likely to have only a small and transient effect on the secretion rate. Cyclic
      AMP also potentiates insulin secretion by an as yet unknown action at a distal
      site. A third action of VIP and PACAP is responsible for the continued
      stimulation of insulin secretion after the levels of cyclic AMP and [Ca2+]i have
      returned to basal values. This third pathway, which is identified at present only
      by its sensitivity to low concentrations of wortmannin, plays a major role in the
      prolonged stimulation of insulin release by VIP and PACAP.

PMID- 8993450
TI  - PACAP-type IB receptors mediate stimulation of phosphoinositide metabolism in
      mouse neuroblastoma cells, clone N1E-115.

PMID- 8993451
TI  - Multiple human receptors for pituitary adenylyl cyclase-activating polypeptide
      and vasoactive intestinal peptide are expressed in a tissue-specific manner.

PMID- 8993452
TI  - Effects of PACAP and VIP on adrenal progesterone release.

PMID- 8993453
TI  - Effect of PACAP, VIP, glucagon, and GLP1 on cAMP production and insulin release
      of HIT-T15 cells is passage dependent.

PMID- 8993454
TI  - Pituitary adenylate cyclase-activating polypeptide: a potent activator of human
      intestinal ion transport.
AB  - To investigate the effects of PACAP-27 on electrolyte transport across the
      isolated human intestinal mucosa, changes in short-circuit current (Isc) were
      measured in Ussing chamber experiments. Serosally added PACAP-27 increased Isc in
      a concentration-dependent manner, eliciting a similar maximal effect in both the
      jejunal and the colonic mucosa. Bumetanide inhibited Isc responses, indicating
      stimulation of Cl- secretion. The potency and efficacy of PACAP-27 were
      comparable to those of VIP, suggesting that both peptides activate intestinal
      secretion by way of a common receptor located in the basolateral membrane of the
      intestinal epithelium.

PMID- 8993455
TI  - New aspects of the neuroendocrine role of PACAP.
AB  - The presence of PACAP was revealed in the anterior pituitary with RIA, HPLC, and
      with the demonstration of its mRNA. The level of PACAP mRNA in the anterior
      pituitary is the highest during the proestrous LH surge. In our
      immunohistochemical studies we were able to demonstrate PACAP immunoreactive
      cells in the anterior pituitary. The shape and the distribution of PACAP
      immunoreactive cells were very similar to that of the gonadotropes; however, the
      number of PACAP cells was less than that of LH cells. Additionally, another PACAP
      positive cell population with small diameter appeared in the proestrous stage,
      during pregnancy and lactation. Double labeling revealed that the major part of
      large PACAP cells exhibited LH immunoreactivity and those with a small diameter
      contained PRL. It is not clear whether the pituitary- or the hypothalamic-born
      PACAP, or both, influence pituitary LH and PRL secretion. I.c.v. administration
      of PACAP just prior to the critical period in the proestrous stage inhibited the
      expected ovulation and blocked the proestrus LH and PRL surge, although i.v.
      administration of PACAP had no effect. PACAP antiserum did not interfere with
      ovulation when i.c.v. or i.v. injection was used. Our results support the view
      that PACAP has a role in the control of LH and PRL secretion during the estrous
      cycle, pregnancy, and lactation. The inhibitory effect of PACAP on ovulation is
      mediated through the hypothalamus.

PMID- 8993456
TI  - Opposite gastric motor effects of PACAP38 and VIP when microinjected into the
      nucleus raphe obscurus of rats.

PMID- 8993457
TI  - VIP- and PACAP-containing nerve fibers in human parathyroid glands and adenomas:
      comparison of innervation pattern with animal species.

PMID- 8993458
TI  - Effect of PACAP on ion channels involved in stimulating growth hormone secretion
      from the somatotrophs.

PMID- 8993459
TI  - Pituitary adenylate cyclase-activating polypeptide and its type I receptors in
      the rat hypothalamus: neuroendocrine interactions.

PMID- 8993461
TI  - Effect of pituitary adenylate cyclase-activating polypeptide on GH gene
      expression in rat pituitary cells.

PMID- 8993460
TI  - Localization of pituitary adenylate cyclase-activating polypeptide and its type I
      receptors in the rat ovary: immunohistochemistry and in situ hybridization.

PMID- 8993462
TI  - Vasoactive intestinal polypeptide as a chemical messenger in the neural control
      of the pacemaker activities of the circular muscle coat in the canine proximal
      colon.

PMID- 8993463
TI  - Pituitary adenylate cyclase-activating polypeptide regulates both adrenocortical
      and chromaffin cell activity in the frog adrenal gland.

PMID- 8993464
TI  - Vasoactive intestinal polypeptide inhibits the established allergic contact
      dermatitis in humans.
AB  - There is increasing evidence indicating that the nervous system influences the
      immune response. In the present study the potential immunomodulatory role of
      vasoactive intestinal polypeptide (VIP) in established allergic contact
      dermatitis in humans was investigated. Positive patch-test reactions were
      elicited by application of nickel sulphate for 48 h. VIP was applied under patch
      test conditions after another 24-h period. The test areas were measured before
      and 24 h after application of VIP and biopsy specimens were taken for
      immunohistochemistry. After application of VIP at 10(-5) mol/L, there was a
      significant reduction in the diameter of the test reaction. In addition, there
      was a reduction in the number of Leu 3a+ cells. The influence of VIP on the
      proliferative response of peripheral blood mononuclear cells from nickel-allergic
      subjects to nickel sulphate was also tested. The cells were cultured for 6 days
      and VIP was added after 3 days. There was no effect on the proliferative
      response. However, when VIP was added at 10(-6) and 10(-5) mol/L, a higher level
      of interferon gamma was found in the nickel-treated cell cultures compared to the
      controls. In conclusion, VIP may have an inhibitory effect on established
      allergic contact dermatitis. This inhibitory effect is possibly mediated through
      an increased production of interferon gamma by peripheral blood mononuclear
      cells.

PMID- 8993465
TI  - PACAP-preferring receptors in human hyperplastic prostate.

PMID- 8993466
TI  - Angiotensin-converting enzyme inhibition with enalapril increases the cardiac
      concentration of vasoactive intestinal peptide.
AB  - In patients with congestive cardiac failure, treatment with ACE inhibitors
      results in peripheral vasodilatation and an increase in cardiac output without an
      increase in heart rate, which suggests a positive inotropic effect. This cannot
      be explained by the changes in angiotensin II and bradykinin concentrations that
      occur. It has been suggested that ACE also metabolizes VIP, which is a positive
      inotrope. As VIP is synthetized by the heart and acts locally to increase cardiac
      output, we postulated that ACE inhibition would increase the myocardial
      concentration of VIP. Male Sprague-Dawley rats received enalapril (2 mg/kg/day)
      in the drinking water or no therapy for seven days. On day seven they were
      anaesthetized and blood sampled. The hearts and kidneys were then harvested and
      snap frozen by immersion in liquid nitrogen. Concentrations of VIP in plasma and
      tissue extracts were measured by radioimmunoassay. Plasma and renal
      concentrations of VIP did not change in the enalapril-treated rats. However, the
      myocardial concentration of VIP increased significantly in the rats receiving
      enalapril compared with control animals (p < 0.0005). We conclude that treatment
      with ACE inhibitors results in increased myocardial VIP concentrations and
      suggest that this may contribute to the improvement in cardiac function that
      occurs with these agents.

PMID- 8993467
TI  - Correlation of vasoactive intestinal peptide and nitric oxide synthase with
      choline acetyltransferase in the airway innervation.
AB  - Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are potent mediators of
      neural airway smooth muscle relaxation. The major contractile mediator released
      by airway nerves under physiological conditions is acetylcholine (ACh). In the
      present study, we have correlated the immunohistochemical distribution of the
      relaxant mediators using antisera to VIP, to the marker enzyme of catecholamine
      synthesis tyrosine hydroxylase (TH) and to the NO-generating enzyme NO-synthase
      (NOS) with the distribution of the ACh-synthesizing enzyme, choline
      acetyltransferase (ChAT), and of substance P (SP), a neuropeptide present in
      sensory nerve fibers. In guinea-pig airways, VIP- and NOS-immunoreactivity (IR)
      were present in numerous nerve fibers in the airway smooth muscle and around
      submucosal glands; some fibers were also seen in the lamina propria and around
      blood vessels. The neuronal cell bodies in the intrinsic ganglia were devoid of
      both VIP- and NOS-IR. In contrast, all neuronal cell bodies in the intrinsic
      ganglia were immunoreactive for ChAT. In human airways, immunoreactivity for VIP,
      NOS, and ChAT was found in airway intrinsic neuronal perikarya. Whereas ChAT-IR
      appeared to be most frequent in the cell bodies, VIP-IR was seen in the largest
      number of nerve fibers in the airways. Therefore, in guinea pigs, a clear
      neuroanatomical and neurochemical separation of relaxant and of constrictor
      pathways is seen, whereas in human airways, both separate pathways as well as
      coexpression of VIP-/NOS- and of ChAT-IR are found.

PMID- 8993468
TI  - Modulation of cyclic AMP and inositol phosphate production in rat prostatic
      cultures by VIP/PACAP, ATP, and carbachol: role in prostatic proliferation.

PMID- 8993469
TI  - On the effects of glucagon-like peptide-1 on blood glucose regulation in normal
      and diabetic subjects.

PMID- 8993470
TI  - Perfusion of the paraventricular nucleus with pituitary adenylate cyclase
      activating polypeptide and vasoactive intestinal polypeptide stimulates local
      release of norepinephrine and its metabolite: microdialysis study in freely
      moving rats.

PMID- 8993471
TI  - Highly sensitive nonisotopic immunoassay for PACAP-27 using various detection
      methods.

PMID- 8993472
TI  - Adenylate cyclase activation by VIP and PACAP in the retina and choroid: effects
      of antagonists.

PMID- 8993473
TI  - In vitro identification of VIP receptors in human tumors: potential clinical
      implications.

PMID- 8993474
TI  - Identification of novel growth-related genes linked to the mitogenic effect of
      PACAP on the rat pancreatic acinar cell line, AR4-2J.
AB  - The mRNA differential display technique was employed in order to identify novel
      growth-related genes linked to the mitogenic effect of PACAP on AR4-2J cells.
      Hereby, three differentially expressed and PACAP-inducible genes were found, one
      of these being homologous to a recently discovered putative growth-related early
      response gene in mice. In AR4-2J cells, mRNA levels of this novel rat gene are
      increased by PACAP in a rapid and transient fashion. This effect was enhanced by
      cycloheximide, whereas actinomycin D prevented the stimulatory effect of PACAP.

PMID- 8993475
TI  - Down-regulation of cytokine expression in murine lymphocytes by PACAP and VIP.
AB  - Neuropeptides, such as VIP and PACAP, released or produced in the
      microenvironment of the primary and secondary lymphoid organs, could affect a
      variety of immune responses through the regulation of cytokine expression. VIP
      has been previously shown to inhibit IL-2, IL-4, and IL-10 production in murine
      lymphocytes stimulated through the TCR-associated CD3 complex. This study shows
      that, similar to VIP, PACAP-38 inhibits IL-2 production in T lymphocytes.
      Comparisons with forskolin, a known cAMP inducer, suggest that the increase in
      intracellular cAMP represents at least one of the transduction pathways involved
      in IL-2 inhibition, especially in the higher range of neuropeptide concentration.
      Studies of the detailed molecular mechanisms involved in the regulation of IL-2
      expression indicate that reduction of de novo transcription and destabilization
      of the message contribute to the reduction of steady-state IL-2 mRNA levels
      following VIP treatment. Examination of several IL-2 transcriptional factors
      indicates that only NFAT is down-regulated by VIP. Neuropeptides, such as VIP and
      PACAP, which specifically modulate the expression of various cytokines, could
      play an important role in the intricate cytokine network controlling local immune
      responses.

PMID- 8993476
TI  - PACAP occurs in sensory nerve fibers and participates in ocular inflammation in
      the rabbit.
AB  - PACAP is a sensory neuropeptide; it occurs together with CGRP in a population of
      C fibers in the rabbit eye. PACAP is likely to be involved in the inflammatory
      response in as much as PACAP-induced responses mimic the symptoms of inflammation
      and because the concentration of PACAP-LI in the aqueous humor increased greatly
      in response to noxious stimuli. The observation that capsaicin releases both
      PACAP and CGRP from the iris and ciliary body supports the view that PACAP is
      present in C fibers in the rabbit eye.

PMID- 8993477
TI  - The effect of neuropeptides on vessel tone and cAMP production.
AB  - The effect of VIP, PHM, PHV, PACAP-27, and PACAP-38 on vessel tone and cAMP
      production was investigated in rabbit ovarian arteries in vitro. The peptides
      (10(-7)M) induced a significant relaxation on NA-precontracted vessels and
      displayed similar potencies. The cAMP accumulation induced by PACAP-27 and PACAP
      38 was five times higher than the cAMP content induced by VIP, PHM, and PHV. NPY
      (10(-7)M) markedly reversed the relaxations induced by VIP, PHM, PHV, PACAP-27,
      and PACAP-38 but did not at all affect the cAMP production induced by these
      peptides. We conclude that the relaxation induced by VIP, PHM, PHV, PACAP-27, and
      PACAP-38 and the contraction evoked by NPY are not solely related to the changes
      of cAMP contents, and that in addition to cAMP, another intracellular signal
      transduction pathway may be involved.

PMID- 8993478
TI  - Epidemiological, clinical, and neuropathological study of apolipoprotein E
      genotype in Alzheimer's disease.
AB  - Our studies of the APOE genotype in AD confirm a strong association of the
      epsilon 4 allele with development of AD and a decreased risk associated with
      epsilon 2. From a clinical/neuropathological perspective, the major effects of
      APOE epsilon 4 are to lower the age of onset and to increase the amount of A beta
      deposit in the brain. Neither rate of progression nor number of neurofibrillary
      tangles were affected. We also carried out a longitudinal population-based
      assessment of the APOE genotype to determine the risk for developing cognitive
      impairment of someone in the general population based on APOE genotype. APOE
      epsilon 4 carried about 1.4-fold increased risk, and APOE epsilon 2 about 1.7
      fold decreased risk. Thus, inheritance of APOE epsilon 4 is a major biological
      risk factor for AD, but it has limited utility as a prognostic indicator for
      development of dementia in an individual.

PMID- 8993479
TI  - Effect of age, ethnicity, and head injury on the association between APOE
      genotypes and Alzheimer's disease.
AB  - The association between apolipoprotein E (APOE)-epsilon 4 and Alzheimer's disease
      has been confirmed worldwide. We and others have observed a diminished
      association in the very old and among African-Americans compared to Caucasians
      and Hispanics in New York. In this review we describe a new method we developed
      to compare relative risks by APOE genotypes in an expanded cohort of cases and
      controls from three ethnic groups in a New York City community and discuss the
      association as between APOE epsilon 4 and Alzheimer's disease as modified by head
      injury. Compared to persons with APOE epsilon 3/epsilon 3 genotypes, relative
      risk (RR) for Alzheimer's disease associated with APOE epsilon 4 homozygosity was
      similar across ethnic groups (African-American RR = 3.3; 95% c.i. 1.6-6.8;
      Caucasian RR = 5.3; 1.6-16.0; Hispanic RR = 2.5; 1.1-5.8). The risk was also
      increased for APOE epsilon 4 heterozygous Caucasians (RR = 3.2; 1.8-5.8) and
      Hispanics (RR 1.5; 1.0-2.2) but not African-Americans (RR = 0.6; 0.4-0.9). Risk
      of AD was not significantly diminished for individuals in any group with APOE
      epsilon 2/epsilon 2 or -epsilon 2/epsilon 3 genotypes. A 10-fold increase in the
      risk of Alzheimer's disease was associated with both APOE epsilon 4 and a history
      of traumatic head injury, compared to a twofold increase in risk with APOE
      epsilon 4 alone. Head injury in the absence of an APOE epsilon 4 allele did not
      increase risk. These results imply that in Alzheimer's disease genotypic risk
      associated with APOE may be influenced by age, ethnicity, and certain
      environmental factors.

PMID- 8993480
TI  - Familial and population-based studies of apolipoprotein E and Alzheimer's
      disease.
AB  - The finding of an association between the epsilon 4 allele of the APOE locus and
      the early expression of late-onset Alzheimer's disease (AD) is robust. However,
      the estimates of the proportion of AD cases carrying one or more copies of the
      epsilon 4 allele vary dramatically between studies (highest estimates being 180%
      of lowest ones). Here we compare the results of association studies in samples
      drawn from an epidemiologically based study design and samples drawn from
      families selected for linkage studies. The significant differences between
      results probably point to the unwitting selection of familial factors other than
      the APOE locus in the family history positive samples. We conclude that any
      selection procedure tending to enrich samples for positive family history will
      also tend to artificially increase APOE epsilon 4 allele frequencies in probands.
      This is of significance in samples drawn from clinical settings where referral
      may be influenced by previous known family history. Further work is needed to
      clarify the nature of the additional factors operating within families. We also
      report data showing an association between late-onset AD and a polymorphism in an
      adjacent locus to APOE-the APOCI locus. As no additional risk for AD can be
      attributed to the APOCI locus, the most likely explanation for the association
      between AD and APOCI is the disequilibrium between the APOCI and APOE loci.
      Therefore, there are likely to be other genetic markers in the area that can be
      used in the same way as APOE as a marker of risk for the disease.

PMID- 8993481
TI  - Polygenic determinants of Alzheimer's disease: modulation of the risk by alpha-1
      antichymotrypsin.
AB  - The identification of apolipoprotein E (APOE) as a genetic risk factor modifying
      the chances of developing Alzheimer's disease (AD) has opened the possibility
      that other susceptibility genes exist that either independently modify the risk
      of developing AD or alter the risk imparted by APOE. We have identified alpha-1
      antichymotrypsin (ACT) as a potential risk gene, by virtue of the interactive
      effect of either of its two alleles (A and T) on the risk of AD associated with
      the APOE epsilon 4 allele. In a large population of AD (n = 308) and control (n =
      579) cohorts, we found the expected elevation in the APOE epsilon 4 allele
      frequency in the AD cases compared to controls, with threefold and sevenfold
      increases in the risk of AD for APOE epsilon 4/X and APOE epsilon 4/epsilon 4,
      respectively. Of the three ACT genotypes, the ACT A/T genotype did not affect the
      risk of AD beyond that which is conferred by the APOE epsilon 4 allele. However,
      the ACT A/A genotype greatly increased the risk associated with APOE epsilon 4
      homozygosity. On the other hand, the ACT T/T genotype suppressed the gene dosage
      effect of the APOE epsilon 4 allele; the risk of AD in APOE epsilon 4/epsilon 4,
      ACT T/T cases was the same as that of APOE epsilon 4/X. A variety of potential
      mechanisms for interactions of ACT and APOE are discussed.

PMID- 8993483
TI  - Apolipoprotein E, A beta-amyloid, and the molecular pathology of Alzheimer's
      disease. Therapeutic implications.

PMID- 8993482
TI  - No association between alpha 1-antichymotrypsin and familial Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common mid to late age-of-onset
      neurodegenerative disorder. AD has a strong and complex genetic etiology, and
      multiple genes, acting independently and/or interacting, likely affect the risk
      of developing AD. Several genes involved with AD already have been described, but
      only the APOE gene on chromosome 19q has been shown to affect the risk of the
      most common form of AD, occurring with onset over the age of 65. Because a
      substantial portion of late-onset AD is not explained by APOE, other genes
      affecting late-onset AD likely occur. These could act either independently or
      perhaps interact with APOE. alpha 1-Antichymotrypsin (ACT) is a major component
      of the amyloid plaques found in the brains of AD patients and may play a role in
      the pathophysiology of AD. It has been proposed that a specific polymorphism
      within the ACT gene interacts with APOE to increase the risk of developing AD.
      Our results do not confirm this finding.

PMID- 8993484
TI  - Apolipoprotein E and Alzheimer's disease. A rapidly expanding field with medical
      and epidemiological consequences.
AB  - The Alzheimer's Association and the National Institute on Aging sponsored a
      meeting of experts in Alzheimer's disease (AD), geneticists, social scientists,
      and ethicists in Chicago in October 1995 to discuss the use of apolipoprotein E
      (APOE) genotyping in Alzheimer's disease. A short scientific report was published
      in the scientific journal Lancet with recommendations from the group. Several
      areas were discussed, including: (1) the scientific basis for recommendations on
      the application and uses of APOE genotyping, (2) clarifying the clinical and
      epidemiological research that needs to done, (3) genetic counseling issues, (4)
      ethical and legal issues, and (5) potential uses of APOE genotyping for treatment
      care planning. This contribution was a general introduction to begin the meeting.
      The genetic association of APOE genotypes with the age of onset distribution and
      risk of Alzheimer's disease was reviewed. An analysis of the current applications
      for three distinctly different applications of APOE genotyping was presented with
      the following conclusions: (1) predictive testing for cognitively intact persons
      was not recommended; (2) APOE genotyping is a promising adjunct for use in the
      differential diagnosis of patients with dementia; and (3) APOE genotyping may
      have a use in selecting therapies; however, further prospective studies are
      necessary. There is no universal "APOE test for AD." A strong emphasis was made
      to avoid use of the term in making recommendations regarding APOE genotyping
      without specific reference to the type of application involved. The predictive
      testing of asymptomatic persons versus APOE genotyping as a diagnostic adjunct
      for symptomatic patients has been seriously confused in both the lay and clinical
      press. The former application is not recommended, but diagnostic usefulness early
      in clinical evaluations for dementia has been confirmed.

PMID- 8993485
TI  - Predictive value of APOE genotyping in incipient Alzheimer's disease.
AB  - The Mayo Alzheimer's Disease Center/Alzheimer's Disease Patient Registry is a
      prospective, longitudinal project of aging and dementia in a community setting.
      Over 400 pairs of individuals have been studied through this project, and
      extensive data on clinical, radiological, neuropathological, and biological
      variables have been gathered. Previous case-control studies on this group of
      subjects have documented the role of the apolipoprotein E (APOE) epsilon 4 as a
      risk factor for dementia. Subsequent analyses between APOE and the age of the
      patients with dementia have shown that most of the epsilon 4 effect is manifest
      in subjects under 75 years of age. We have also used this patient resource to
      study a group of individuals who are at risk for dementia by virtue of having a
      significant memory impairment. We have designated these patients as having a mild
      cognitive impairment because they have abnormal memory function but do not reach
      criteria for dementia. Over the course of several years of follow-up, these
      subjects evolve to dementia at a rate of approximately 15% per year. The presence
      of an APOE epsilon 4 carrier status is the best predictor of subsequent
      development of dementia in these individuals. These studies indicate that APOE is
      an important risk factor for AD, and in patients with a mild cognitive
      impairment, APOE may be useful in predicting who is likely to progress to
      dementia.

PMID- 8993486
TI  - Early detection of Alzheimer's disease by combining apolipoprotein E and
      neuroimaging.
AB  - New treatments for Alzheimer's disease (AD) are more likely to slow or halt
      disease progression rather than to reverse existing neuronal damage. Identifying
      persons with mild cognitive complaints who are at risk for AD will allow
      investigators to apply anti-dementia treatments before extensive brain damage
      develops. The discovery of the apolipoprotein E epsilon 4 allele (APOE epsilon 4)
      as a major risk factor for AD offers promise of assisting in early detection and
      prediction of Alzheimer's disease, particularly when genetic assessments are
      combined with other biomarkers such as neuroimaging. Studies of relatives at risk
      for familial AD using neuroimaging (positron emission tomography [PET]) and
      genetic assessments of APOE suggest that at-risk relatives with APOE epsilon 4
      have lower parietal metabolism than those without APOE epsilon 4. Additional
      techniques that might increase sensitivity and specificity include longitudinal
      assessment of clinical and brain functional change, pharmacological challenges of
      short-acting anticholinergic agents, and memory activation paradigms during
      functional scanning. Such strategies should eventually assist in early detection
      of AD and in vivo therapeutic monitoring of brain function during experimental
      anti-dementia treatment trials.

PMID- 8993487
TI  - The use of apolipoprotein E genotyping as a diagnostic test in suspected
      Alzheimer's disease.

PMID- 8993488
TI  - The effect of apolipoprotein E genotype on biochemical markers of Alzheimer's
      disease.

PMID- 8993489
TI  - Apolipoprotein E genotype and gender influence response to tacrine therapy.
AB  - Our objective is to evaluate the effects of apolipoprotein E genotype (APOE) on
      clinical response to treatment with tacrine, in patients with Alzheimer's disease
      (AD). Only 25 to 50% of patients with AD, depending on dose and design, have been
      responders in previous tacrine trials. AD autopsy studies have suggested that
      APOE epsilon 4 is associated with decreased numbers of cholinergic markers in
      temporal cortex and the hippocampus. Our hypothesis was that cholinergic therapy
      might be less effective in epsilon 4 carriers. APOE phenotypes were determined
      from plasma samples previously saved from a large 30-week, randomized, double
      blind placebo-controlled, parallel-group, multicenter trial of tacrine at dosages
      of 80, 120, or 160 mg/day. Outcome measures included Alzheimer's Disease
      Assessment Scale (ADAS) and its cognitive component (ADAS-Cog), Clinician's
      Interview-Based Impression (CIBI), Global Deterioration Scale (GDS), and the
      caregiver-rated Clinical Global Impression of Change (CGIC). Analyses were
      performed on the change in scores from baseline to last observation on 460
      patients having APOE results available. There were 291 patients heterozygous or
      homozygous for APOE epsilon 4 and 169 patients with only APOE epsilon 2 or
      epsilon 3 alleles. Analysis of variance showed non-APOE epsilon 4 carriers (E2,3)
      on tacrine improved more versus placebo than patients with APOE epsilon 4 (E4) on
      tacrine versus placebo as measured by the ADAS (p = 0.04) and the ADAS-Cog (p =
      0.05). A trend toward greater treatment effect in the E2,3 patients was seen with
      CIBI, GDS, and CGIC, but these differences did not achieve significance. APOE
      genotype may be a predictor for clinical response to tacrine in AD patients, APOE
      epsilon 4 associated with a lower probability of cognitive improvement. When the
      groups were further divided by gender, most of the effect of APOE on treatment
      response was seen in women. E2-3 women improved more than any other group, and E4
      women the least. The interaction of gender and APOE genotype on treatment
      response as measured by ADAS-Cog was significant (p = 0.03). Future trials of
      cholinergic therapy in AD should include APOE genotyping.

PMID- 8993490
TI  - On not jumping the gun: ethical aspects of APOE gene testing for Alzheimer's
      disease.

PMID- 8993491
TI  - A pilot experience in genetic counseling for Alzheimer's disease. Findings
      relevant to the potential use of APOE genotyping in cognitively impaired
      individuals.

PMID- 8993492
TI  - Just caring: the moral and economic costs of APOE genotyping for Alzheimer's
      disease.

PMID- 8993493
TI  - Medicolegal, employment, and insurance issues in APOE genotyping and Alzheimer's
      disease.

PMID- 8993494
TI  - The National Institute on Aging/Alzheimer's Association recommendations on the
      application of apolipoprotein E genotyping to Alzheimer's disease.
AB  - In a conference held in Chicago during October 1995, a working group of the
      National Institute of Aging (NIA) and the Alzheimer's Association (AlzA) drafted
      consensus recommendations on research and clinical applications of APOE genetic
      susceptibility testing for Alzheimer's disease (AD). The NIA/AlzA Working Group
      concluded that in considering future applications of APOE genotyping and other
      knowledge that has been gained about the genetic basis of AD, the interests of AD
      patients and their family members must be held paramount. The group acknowledged
      that a robust association exists between possession of the APOE epsilon 4 allele
      and the risk of late-onset AD and cited evidence that this allele is more
      strongly associated with AD than any other form of dementia. They recommended
      against the use of APOE genotyping to predict the-future development of AD in
      asymptomatic individuals at this time, and warned against the use of the test in
      isolation as the sole means for diagnosing AD. The group endorsed the concept of
      discretionary use of APOE genotyping as an adjunct to other AD diagnostic
      procedures. However, routine clinical use of the test for this purpose was not
      recommended at this time. Physicians were advised to weigh any potential benefits
      of testing against the possibility that genotype disclosure could adversely
      affect the insurability, employability, and social standing of AD patients and
      their family members. Adequate provisions for pre-test and post-test counseling
      and psychosocial support were advised for all future clinical and research
      applications of APOE genotyping. The group called for the development of improved
      protocols for AD genetic counseling as well as supplemental measures to assure
      genetic privacy for AD patients and their family members.

PMID- 8993495
TI  - Camptothecin. Discovery to clinic.

PMID- 8993496
TI  - Synthesis of CPT-11 (irinotecan hydrochloride trihydrate).

PMID- 8993497
TI  - Chemistry of the camptothecins in the bloodstream. Drug stabilization and
      optimization of activity.

PMID- 8993499
TI  - Mechanism of action of camptothecin.

PMID- 8993498
TI  - Using yeast to understand drugs that target topoisomerases.

PMID- 8993500
TI  - The effect of camptothecin on topoisomerase I catalysis.
AB  - The existence of a covalent intermediate in topoisomerase I catalysis allows
      uncoupling of the cleavage and ligation half-reactions on partially single
      stranded DNA substrates containing a highly preferred interaction site. Using
      this model DNA substrate system we have demonstrated that the cleavage reaction
      requires bipartite interaction with two distinct DNA duplex regions; One located
      around the cleavage site (region A) and another located on the side holding the
      5'-OH end generated by cleavage (region B). The postcleavage complexes containing
      the enzyme covalently attached at an internal position are capable of ligating
      DNA strands matching the noncleaved strand. Previously, we have characterized the
      effect of the antitumor agent camptothecin on the two half-reactions of
      topoisomerase I catalysis on DNA substrates allowing bipartite DNA interaction.
      The obtained results demonstrated that the drug only inhibited the ligation
      reaction leaving the cleavage reaction unaffected at the studied site. Here, we
      report that camptothecin also impairs ligation of the cleaved strand to a
      dinucleotide within region A in the absence of additional DNA contacts. When
      these results are taken together with the observation that camptothecin-trapped
      topoisomerase I-DNA complexes preferentially are generated at sites containing
      guanine immediately 3' to the cleavage position, it suggests that camptothecin
      inhibits the ligation reaction by forming a reversible ternary complex with the
      enzyme and DNA at the cleavage site within region A.

PMID- 8993501
TI  - Cellular resistance to camptothecins.

PMID- 8993503
TI  - The cell cycle effects of camptothecin.

PMID- 8993502
TI  - Camptothecin resistance related to drug-induced down-regulation of topoisomerase
      I and to steps occurring after the formation of protein-linked DNA breaks.

PMID- 8993504
TI  - Induction of apoptosis by camptothecin and topotecan.

PMID- 8993505
TI  - Identification of topoisomerase I mutations affecting both DNA cleavage and
      interaction with camptothecin.

PMID- 8993506
TI  - Factors affecting topotecan sensitivity in human leukemia samples.

PMID- 8993507
TI  - Induction of apoptosis in malignant and camptothecin-resistant human cells.
AB  - Flow cytometry studies demonstrate that androgen-independent human prostate
      carcinoma DU-145 cells are arrested at the G1-phase of the cell cycle in the
      presence of suramin, but they die by apoptosis in the presence of 9
      nitrocamptothecin (9NC). The addition of cytostatic concentrations of suramin
      increases the apoptotic action of 9NC on DU-145 cells, and induces apoptosis in
      9NC-resistant DU-145/RC cells that were derived from the parental DU-145 cells by
      continuous exposure to progressively increased concentrations of 9NC. In
      addition, the topoisomerase II-directed drug etoposide exerts more extensive
      apoptotic action on DU-145/RC than DU-145 cells. Increased resistance of DU-145
      cells to 9 NC and collaterally increased sensitivity to etoposide and suramin
      appear to correlate with alterations in the structure rather than synthesis of
      topoisomerases and possibly with specific cellular proteins that regulate
      apoptosis. The results suggest that etoposide and suramin may be successful
      alternative treatments for 9NC-resistant androgen-independent prostate cancer.

PMID- 8993509
TI  - Clinical pharmacology and pharmacodynamics of irinotecan. A review.

PMID- 8993508
TI  - Pharmacokinetics of camptothecins administered orally.
AB  - The equilibrium between lactone and salt forms of camptothecin (CPT) and its
      derivatives including 9-nitrocamptothecin (9-NC) depends on pH, binding to
      albumin and other factors. Their antitumor activity is associated with the
      lactone form. Our goal was the development of dosing regimens optimal for
      chemotherapeutic activity of the drug. The effect of p.o., i.v. and i.m.
      administration on the tumor uptake of [3H]-CPT or [3H]-9-NC in tumor-bearing nude
      mice was studied by whole-body autoradiography. In all cases, [3H]-CPT or [3H]-9
      NC accumulated mainly in the gastrointestinal tract. Comparatively lower levels
      of drug were detected in liver, kidney, tumor, and other sites. Consistently high
      tumor/blood ratios following oral administration of drug suggest this route as
      the most effective way of treatment. Within 4 h of i.s. administration of 2 mg/kg
      CPT or 1 mg/kg 9-NC to mice, lactone forms were 57-81% and 47-95% of total plasma
      drug levels, respectively. However in plasma of humans treated p.o. with varying
      doses of CPT or 9-NC, lactone forms were only a minor component of total drug
      levels. It is concluded that ratios of lactone/total drug are much higher in mice
      than in humans, which influence the therapeutic efficacies these drugs in the two
      species.

PMID- 8993510
TI  - Preclinical antitumor activity and pharmacokinetics of irinotecan (CPT-11) in
      tumor-bearing mice.

PMID- 8993511
TI  - Protocols for the treatment of human tumor xenografts with camptothecins.
AB  - Thirty-five human tumors of various histological types xenografted at various
      sites into nude mice and rats have been used to assess the anticancer activity of
      camptothecin and derivatives administered by different routes (subcutaneous,
      intramuscular, intravenous, intrastomach, and transdermal). Camptothecins are
      active against human tumors at every site including the brain. So far, the best
      anticancer/toxicity ratio has been found with 9-nitrocamptothecin (9NC) and 9
      aminocamptothecin (9AC) to which 9NC converts in the body of mammals. Comparing
      the results obtained during clinical trials with the animal ones, it is evident
      that camptothecins are much less active in humans than in mice against human
      tumors. This is probably due to the fact that in humans the lactone ring of
      camptotecins opens much faster than in mice. Measurement of the area under the
      curve (AUC) in mice and humans under comparable conditions of administration
      gives values of 3% closed lactone for man versus 55% in mice for 9NC. Clearly
      this is the crucial problem to overcome in order to improve the efficacy of the
      camptothecins as anticancer agents.

PMID- 8993512
TI  - Schedule-dependent efficacy of camptothecins in models of human cancer.

PMID- 8993513
TI  - Topoisomerase I inhibition by the camptothecin analog Gl147211C. From the
      laboratory to the clinic.
AB  - The development of camptothecin-like compounds as inhibitors of DNA topoisomerase
      I for the treatment of solid tumors has generated clinical excitement in this new
      class of drugs. We have discovered, developed, and entered into clinical trial a
      novel, potent, and water-soluble camptothecin analog with significant antitumor
      activity. This compound, Gl147211C [7-(4-methylpiperaziinomethylene)-10, 11
      ethylenedioxy-20(S)-camptothecin hydrochloride] is a specific inhibitor of DNA
      topoisomerase I. Compared to topotecan, Gl147211C is approximately three times as
      potent in the cleavable complex assay and approximately twice as soluble in
      aqueous medium. Human tumor cell line cytotoxicity assays indicated that
      Gl147211C was approximately 3- to 5-fold more potent than topotecan, while both
      compounds were relatively insensitive to the multidrug resistance P-glycoprotein.
      The in vivo preclinical antitumor activity of Gl147211C was compared to topotecan
      in an array of human tumor xenograft models in nude mice. In general, Gl147211C
      was able to induce regression of established tumors whereas topotecan was not.
      Microscopic evaluation of necropsied tissues indicated that drug-induced toxicity
      was mild, primarily limited to the gastrointestinal tract, and was comparable for
      both Gl147211C and topotecan. Based on these observations, Gl147211C moved
      through preclinical development and subsequently into Phase I clinical trial. A
      summary of Phase I trial results to date is provided.

PMID- 8993514
TI  - Treatment of central nervous system xenografts with camptothecins.

PMID- 8993515
TI  - Camptothecin and its analogs. An overview of their potential in cancer
      therapeutics.
AB  - From the outset of their clinical testing the camptothecins have shown antitumor
      activity against gastrointestinal cancer. With the definition of mechanism of
      action and introduction of several analogs their antitumor activity spectrum has
      expanded to include ovarian, cervical, small-cell and non-small cell lung cancers
      and malignant lymphomas, among others. The wide range of trials in these disease
      areas have been reviewed for CPT-11, topotecan, and 9-aminocamptothecin. A
      therapeutic role is anticipated for these and other camptothecins in these
      disease sites. Issues in guiding treatment indications and clinical development
      include: 1) pharmacokinetics and scheduling relevant to each of the drugs, with
      the oral route emerging as a practical way for testing prolonged exposure; 2)
      dose-intensification with cytokines, and its relevance in maintaining effective
      doses particularly in combination with other myelosuppressive drugs; and 3)
      pharmacodynamic determinants of response-an area of research that is particularly
      attractive because topoisomerase I is the target for camptothecins.

PMID- 8993516
TI  - Phase I clinical and pharmacological studies of 20-(S)-camptothecin and 20-(S)-9
      nitrocamptothecin as anticancer agents.
AB  - Groups of 52 and 29 patients with refractory cancers received either native
      camptothecin (CPT) or 9-nitrocamptothecin (9NC), respectively, in Phase I
      clinical trials designed to determine the maximum tolerated dose, toxicity and
      potential efficacy of orally administered camptothecins. Favorable responses
      occurred with both compounds (11% after CPT, 24% after 9NC). Although both agents
      could be taken safely for extended periods, dose limiting toxicities were
      substantial. Diarrhea was the major clinical problem with CPT, and
      myelosuppression with 9NC. Both compounds could cause hemorrhagic cystitis. The
      antitumor activity demonstrated suggests that further investigation of orally
      administered camptothecin analogs is warranted.

PMID- 8993517
TI  - 9-Aminocamptothecin and beyond. Preclinical and clinical studies.

PMID- 8993518
TI  - Trials of 9-amino-20(S)-camptothecin in Boston.
AB  - 9-Amino-20(S)-camptothecin (9-AC) is an analog of camptothecin with limited water
      solubility which has shown significant preclinical activity in a variety of human
      solid tumor xenografts. A Phase I trial using a soluble formulation of 9-AC,
      given as a 72-hour continuous infusion, has been completed. Thirty-one patients
      with resistant cancers received 5-60 micrograms/M2/h at three week intervals. The
      Maximum Tolerated Dose (MTD) was 45 micrograms/M2/hour. Neutropenia was the dose
      limiting toxicity, with few significant non-myelosuppressive toxicities. Minor
      responses were seen in 3/31 patients. Pharmacokinetic studies of 9-AC lactone
      (closed ring) showed substantial interpatient variability with a predicted half
      life of 36 hours. A phase I/II trial of the same formulation of 9-AC is ongoing
      in refractory leukemia. Stomatitis and diarrhea are the non-myelosuppressive dose
      limiting toxicities. Evidence of antineoplastic activity has been seen in 3/15
      patients. A Phase II trial in previously untreated metastatic breast cancer is
      also underway. A Phase I trial of a colloidal dispersion formulation, not yet
      completed, is better tolerated with a MTD > 45 micrograms/M2/h as a 72-hour
      continuous infusion. Evidence of antineoplastic activity has also been
      demonstrated.

PMID- 8993519
TI  - Topoisomerase-I inhibitors in the management of colon cancer.

PMID- 8993520
TI  - Clinical studies of topotecan.

PMID- 8993521
TI  - The current status of irinotecan (CPT-11) in the United States.

PMID- 8993522
TI  - CPT-11. The European experience.
AB  - CPT-11 is a derivative of camptothecin, which has a broad spectrum of antitumor
      activity, both in vitro and in vivo. Like camptothecin, CPT-11 is a selective
      inhibitor of the DNA enzyme topoisomerase I. Phase I trials were conducted in
      Europe with the aim of determining the recommended CPT-11 dose and schedule for
      evaluation in phase II trials. The phase I trials assessed the toxicity of CPT-11
      in 235 patients and tested three different administration schedules. CPT-11 was
      administered as a single infusion once every three weeks, as a weekly infusion
      for three weeks out of every four, and as a daily infusion for three consecutive
      days every three weeks. The maximum tolerated dose (MTD) was 115 mg/m2 in the
      daily schedule and 145 mg/m2 in the weekly schedule. When the drug was
      administered once every three weeks, diarrhea became the dose-limiting toxicity
      at doses above 350 mg/m2. This schedule allowed the highest dose intensity to be
      obtained, was the best tolerated, and allowed ambulant treatment. Finally, using
      this schedule, a combination of CPT-11 with high doses of loperamide allowed the
      dose of CPT-11 to be increased to 750 mg/m2. An ongoing phase I trial is
      investigating the combination of CPT-11 and 5-fluorouracil (5-FU) in various
      solid tumors. Although the MTD has not yet been reached, preliminary results have
      not demonstrated any pharmacokinetic interaction between the two drugs, contrary
      to the findings of a previous Japanese study. Based on the results of the three
      phase I trials, CPT-11 administered at a dose of 350 mg/m2 as an intravenous
      infusion over 30 minutes once every three weeks has been recommended for
      assessment in phase II trials. The phase II trials started in Europe at the
      beginning of 1992. To date, CPT-11 has showed remarkable efficacy in colorectal
      cancer, even in patients resistant to 5-FU. Interesting results have also been
      obtained in pancreatic, cervical and lung cancer. Future trials will make it
      possible to assess whether there is a place for CPT-11 in combination with other
      cytotoxic agents or radiotherapy.

PMID- 8993523
TI  - Clinical trials of irinotecan hydrochloride (CPT, campto injection, topotecin
      injection) in Japan.
AB  - CPT-11 was synthesized in 1984 at the laboratory of Yakult Honsha. Phase I study
      of CPT-11 was begun in 1986. The appropriate doses for phase II studies were
      decided to be 100 mg/m2 weekly or 150 mg/m2 every 2 weeks. Phase II study was
      conducted and this drug was approved for NSCLC, SCLC, uterine cancer and ovarian
      cancer by MHW in 1994. It obtained approval for stomach cancer, colorectal
      cancer, breast cancer, skin cancer and non-Hodgkin's lymphoma in 1995. The
      combination chemotherapies including CPT-11 have been conducted by using various
      regimens such as CPT-11 + CDDP, CPT-11 + VP-16, CPT-11 + 5-FU and CBDCA + CPT-11.
      In stage IV SCLC two prospective randomized controlled trials are on going
      comparing CPT-11 vs. CPT-11 + CDDP vs. VDS + CDDP and CPT-11 + CDDP vs. VDS +
      CDDP. In advanced SCLC Japanese Clinical Oncology Group (JCOG) started a
      randomized controlled trial comparing CPT-11 + CDDP vs. VP-16 + CDDP. In stage
      III NSCLC the dose escalation studies of CPT-11 (CPT-11) in the combination with
      TRT are ongoing by JCOG. The problem of CPT-11 in the combination chemotherapy
      and combined modality is that it is quite difficult to increase the dose of CPT
      11 to full dose to obtain the maximum effect.

PMID- 8993524
TI  - Cytotoxic efficacy with combinations of topoisomerase I and topoisomerase II
      inhibitors in sensitive and multidrug-resistant L1210 mouse leukemia cells.

PMID- 8993525
TI  - Failure in DNA elongation predicts sensitivity to camptothecin in the colon cell
      lines of the NCI Anticancer Drug Screen.

PMID- 8993526
TI  - Radiation enhancement by 9-aminocamptothecin. Evidence for improved therapeutic
      ratio with a multiple dose schedule.

PMID- 8993527
TI  - Pharmacokinetic and pharmacodynamic studies of 9-aminocamptothecin in vitro
      against human cancer cells.

PMID- 8993528
TI  - Implications for the use of topoisomerase I inhibitors in treatment of patients
      with systemic sclerosis.

PMID- 8993529
TI  - Lowered phosphorylation of topoisomerase I is a direct reason for reduced
      sensitivity of L5178Y-S cells to camptothecin.

PMID- 8993530
TI  - Clinical pharmacology of 9-aminocamptothecin.

PMID- 8993531
TI  - The peroxisome in retrospect.

PMID- 8993532
TI  - Signals, receptors, and cytosolic factors involved in peroxisomal protein import.
AB  - Peroxisomes are ubiquitous eukaryotic organelles which function in a wide variety
      of metabolic processes. The many lethal human disorders associated with defects
      in peroxisomal protein import underscore the importance of this organelle. In
      recent years, the evolutionarily conserved molecular mechanisms of protein
      targeting to, and translocation across, peroxisomal membranes have begun to
      emerge. Signals which route proteins to the organelle have been identified, as
      have cytosolic, membrane-associated, and lumenal components of the import
      machinery. The goal of this brief review was to summarize our current knowledge
      of some of these molecules and to describe several potential mechanisms by which
      peroxisomes selectively import their constituent proteins. Aspects of these
      mechanisms that distinguish peroxisomal protein import from protein targeting to
      other organelles are highlighted.

PMID- 8993533
TI  - A branched pathway for peroxisomal protein import: S. cerevisiae ghosts and an
      intraperoxisomal PTS2 receptor.

PMID- 8993534
TI  - Protein import into peroxisomes: new developments.

PMID- 8993535
TI  - Peroxisome biogenesis in the yeast Hansenula polymorpha: a structural and
      functional analysis.

PMID- 8993536
TI  - Protein insertion into the peroxisomal membrane.

PMID- 8993537
TI  - Import of stably-folded proteins into peroxisomes.
AB  - By virtue of their synthesis in the cytoplasm, proteins destined for import into
      peroxisomes are obliged to traverse the single membrane of this organelle.
      Because the targeting signal for most peroxisomal matrix proteins is a carboxy
      terminal tripeptide sequence (SKL or its variants), these proteins must remain
      import-competent until their translation is complete. Although the conformational
      requirements for translocation across other cellular membranes are known in some
      detail, they are presently unknown for the peroxisomal membrane. Prefolded
      proteins stabilized with disulfide bonds and chemical cross-linkers were shown to
      be substrates for peroxisomal import, as were mature folded and disulfide-bonded
      IgG molecules containing the peroxisomal targeting signal. In addition, colloidal
      gold particles conjugated to proteins bearing the peroxisomal targeting signal
      were translocated into the peroxisomal matrix. These results support the concept
      that proteins may fold in the cytosol prior to their import into the peroxisome,
      and that protein unfolding is not a prerequisite for peroxisomal import.

PMID- 8993538
TI  - Peroxisomal beta-oxidation: enzymology and molecular biology.

PMID- 8993539
TI  - Functions and organization of peroxisomal beta-oxidation.

PMID- 8993540
TI  - Peroxisomal beta-oxidation and polyunsaturated fatty acids.
AB  - Peroxisomes are capable of oxidizing a variety of substrates including
      (poly)unsaturated enoyl-CoA esters. The beta-oxidation of unsaturated enoyl-CoA
      esters in peroxisomes, and also in mitochondria, is not just chain-shortening but
      also involves the metabolizing of pre-existing carbon-to-carbon double bonds. In
      addition to the enzymes of the beta-oxidation spiral itself, this metabolism
      requires the participation of auxiliary enzymes: delta 3, delta 2-enoyl-CoA
      isomerase; 2,4-dienoyl-CoA reductase; 2-enoyl-CoA hydratase 2 or 3-hydroxyacyl
      CoA epimerase; and delta 3,5 delta 2,4-dienoyl-CoA isomerase. Many of these
      enzymes are present as isoforms, and can be found located in multiple subcellular
      compartments, for example, peroxisomes, mitochondria or the endoplasmic
      reticulum, while some of the activities are integral parts of multifunctional
      enzymes of beta-oxidation systems.

PMID- 8993541
TI  - Lipid biosynthesis in peroxisomes.

PMID- 8993543
TI  - Peroxisomal purine metabolism.

PMID- 8993542
TI  - Cell compartmentalization of cholesterol biosynthesis.
AB  - Thus, the results showing the presence of cholesterol synthetic enzymes in
      peroxisomes (see references 1, 4, 5, 6, 7, 8, 12, 13, 20, 21, 22, 24, 25, and
      26), the reduced levels of cholesterol synthesis enzymes and cholesterol
      synthetic capacity of cells and tissues lacking peroxisomes, 26, 37, 39 and the
      low serum cholesterol levels in patients suffering from peroxisomal deficiency
      diseases40-43 demonstrate that peroxisomes are essential for normal cholesterol
      synthesis. A number of metabolic pathways require co-participation of enzymes
      located in both peroxisomes as well as enzymes found in other intracellular
      compartments. For example, the first steps of plasmalogen synthesis occur in the
      peroxisomes, while the terminal reactions are completed in the endoplasmic
      reticulum. Similarly, the oxidation of cholesterol to bile acids requires the
      participation of enzymes localized in the endoplasmic reticulum as well as
      peroxisomes. Little is known about the regulation of such pathways or about the
      shuttling of intermediates between compartments. The physiological importance of
      peroxisomal enzymes in the regulation of sterol metabolism remains to be
      clarified.

PMID- 8993544
TI  - Peroxisome proliferator-induced pleiotropic responses: pursuit of a phenomenon.

PMID- 8993545
TI  - Analysis of peroxisome proliferator-responsive enhancer of the rat acyl-CoA
      oxidase gene.

PMID- 8993546
TI  - Interplay of the peroxisome proliferator-activated receptor and the thyroid
      hormone receptor-signaling pathways in regulating peroxisome proliferator
      responsive genes.

PMID- 8993547
TI  - PPAR tissue distribution and interactions with other hormone-signaling pathways.

PMID- 8993548
TI  - Peroxisome proliferator-activated receptors: structures and function.
AB  - We have been attempting to elucidate the molecular mechanisms through which
      peroxisome proliferators exert their pleiotropic effects, with particular
      emphasis on understanding why humans appear unresponsive to these compounds.
      There is a wealth of data to implicate the peroxisome proliferator-activated
      receptor alpha (PPAR alpha) in mediating these effects in rodent species; PPAR
      alpha is expressed in tissues that show physiological changes in response to PPs,
      is transcriptionally activated in vitro by a variety of PPs, and it has been
      recently demonstrated that mice lacking this receptor are refractory to the
      effects of clofibrate and Wy-14,643, at least in the short term. It is
      conceivable that differences in PPAR alpha between responsive rodent and
      unresponsive human subjects may provide the key to understanding the basis of
      this species variation in response, and with this in mind we have been studying
      the biology of PPAR alpha in humans and looking at interindividual variation.
      There is already published evidence, albeit on only two sequences, for structural
      and functional polymorphism in human PPAR alphas. We have extended these
      findings, and shown that: There is considerable variation in hPPAR alpha cDNAs
      obtained from different individuals, both at the gross structural level (lack of
      a coding exon) and of a more subtle nature (single base changes leading to amino
      acid substitutions). One such cDNA, the sequence of which differs at only three
      amino acids from that published, encodes a receptor that is incapable of
      transcriptional activation by potent PPs. The degree to which hPPAR alpha
      transcripts are expressed in human livers can vary by up to an order of magnitude
      between individuals. The tissue-specific expression profile of PPAR alpha in
      humans is very different from that in rat and mouse. In particular, the human
      liver contains generally low levels of PPAR alpha in contrast to the responsive
      rodents, in which potent PPs cause liver tumors. Taken together, these data
      suggest first that human and rodent PPAR alphas differ according to a number of
      molecular and biochemical criteria, and secondly that there is a degree of
      interindividual variation in PPAR alpha structure and function. Studies are
      ongoing to clarify this further, but human polymorphism may go some way towards
      explaining the apparent paradox that active PPAR alpha receptors can be isolated
      from an "unresponsive" species.

PMID- 8993549
TI  - The peroxisome proliferator-activated receptors: ligands and activators.
AB  - PPAR alpha and PPAR gamma represent related but distinct members of the nuclear
      receptor superfamily. PPAR alpha signaling is modulated by long-chain fatty
      acids, whereas PPAR gamma ligands are potent antidiabetic agents.

PMID- 8993551
TI  - Induction of peroxisomal enzymes by dehydroepiandrosterone: metabolic activation
      by sulfate conjugation.

PMID- 8993550
TI  - Discovery of ligands for the nuclear peroxisome proliferator-activated receptors.
AB  - The identification of high-affinity ligands for PPAR gamma has revealed the role
      of this receptor as the molecular target for the antidiabetic activity of the
      thiazolidinediones. The surprising observation that agonists of an adipogenic
      transcription factor reverse the obesity-associated disease of diabetes
      highlights the power of using potent and selective ligands to study receptor
      mediated biology. Similarly, the observation that PGD2 and its cyclopentenone
      metabolites compounds are microM PPAR ligands suggests that these receptors may
      have a physiological role in mediating prostaglandin signaling in the spleen.

PMID- 8993552
TI  - Immunocytochemical study of the ultrastructure of peroxisomes and the effects of
      peroxisome proliferators.

PMID- 8993553
TI  - Structural diversity of peroxisome proliferators and their effects on mammalian
      liver cells in vivo.

PMID- 8993554
TI  - Peroxisome proliferators and cytochrome P4504A induction.

PMID- 8993556
TI  - Molecular regulation of peroxisomal acyl-CoA oxidase in yeast.

PMID- 8993555
TI  - Zonal heterogeneity of peroxisome proliferation in rat liver.

PMID- 8993557
TI  - The peroxisome proliferator-activated receptor: transcriptional activation of the
      CYP4A6 gene.

PMID- 8993558
TI  - Common structural requirements for peroxisome proliferation by tetrazole and
      carboxylic acid-containing compounds.

PMID- 8993559
TI  - Peroxisome proliferators and signal transduction.

PMID- 8993560
TI  - Protein phosphorylation by peroxisome proliferators: species-specific stimulation
      of protein kinases and its role in PP-induced transcriptional activation.

PMID- 8993561
TI  - Peroxisomal diseases: a microscopist looks through the retrospectroscope.

PMID- 8993562
TI  - Peroxisomal disorders: overview.

PMID- 8993563
TI  - Peroxisomal disorders: clinical aspects.
AB  - Peroxisomal disorders are divided into two groups from a clinical point of view.
      Diseases in the first group, peroxisome-deficient disorders (PDD), Zellweger-like
      syndrome, and isolated deficiencies of peroxisomal beta-oxidation enzymes, are
      characterized by common clinical features including psychomotor retardation,
      hypotonia, hepatic dysfunction and visual disturbance. The second group includes
      diseases with a unique manifestation, such as X-linked adrenoleukodystrophy,
      hyperoxaluria type I and rhizomelic chondrodysplasia punctata. We investigated
      clinical aspects and the genetic basis of PDD, and the significance of
      peroxisomes in the development of human brain. Neuroradiological and
      neurophysiological studies revealed that thick cortex, colpocephaly and
      multifocal spikes were characteristic findings of PDD patients in the early
      infantile period. Cytogenetic studies elucidated the presence of eleven
      complementation groups among PDD, indicating the presence of eleven pathogenic
      genes for PDD. Molecular studies elucidated two of these genes, PAF-1 and PXR-1.
      Immunohistochemical studies clarified that the catalase-positive neurons appeared
      in the basal ganglia, thalamus, and cerebellum at 28 weeks of gestation, and in
      the cortex at 35 weeks. Immunopositive glial cells appeared from the deep to
      superficial white matter with increasing gestational age. These results suggest
      the important role of peroxisomes in neuronal maturation and myelinogenesis.

PMID- 8993564
TI  - Metabolic aspects of peroxisomal disorders.
AB  - In recent years an increasing number of inherited diseases in man have been
      identified in which there is an impairment in one or more peroxisomal functions.
      This paper discusses the current state of knowledge on these disorders with
      particular emphasis on the metabolic abnormalities in these diseases.

PMID- 8993565
TI  - X-linked adrenoleukodystrophy.

PMID- 8993566
TI  - Targeting of alanine: glyoxylate aminotransferase in normal individuals and its
      mistargeting in patients with primary hyperoxaluria type 1.

PMID- 8993567
TI  - Approaches to studies on peroxisome biogenesis and human peroxisome-deficient
      disorders.

PMID- 8993568
TI  - Peroxisome mosaics in the liver of patients and the regulation of peroxisome
      expression in rat hepatocyte cultures.

PMID- 8993570
TI  - Targeted disruption of the peroxisome proliferator-activated receptor alpha gene,
      PPAR alpha.

PMID- 8993569
TI  - From expressed sequence tags to peroxisome biogenesis disorder genes.
AB  - Isolation of human disease genes is a challenging process and can often only be
      achieved by labor-intensive positional cloning techniques. Fortunately, there are
      alternative strategies for isolation of peroxisome biogenesis disorder genes. The
      first, functional complementation, was established as a viable approach by Fujiki
      and colleagues, who identified PAF-1, the first known peroxisome biogenesis
      disorder gene. The second strategy, computer-based homology probing, relies on
      (1) the fact that peroxisome assembly has been conserved throughout the evolution
      of eukaryotes, (2) knowledge of the amino acid sequences of an increasing number
      of yeast peroxisome assembly (PAS) genes, and (3) the existence of sequence data
      from large numbers of human genes. The recent development of the expressed
      sequence tag (EST) database (dbEST) is fulfilling the last of these requirements.
      We have applied the homology probing strategy in the search for candidate genes
      for the peroxisome biogenesis disorders by routinely screening the database of
      ESTs for genes with significant sequence similarity to yeast PAS genes. The
      validity of this approach is demonstrated by its use in identifying PXR1 as the
      human orthologue of the Pichia pastoris PAS8 gene and PXAAA1 as a human homologue
      of the Pichia pastoris PAS5 gene. Furthermore, detailed analysis of PXR1 has
      revealed that mutations in this gene are responsible for complementation group 2
      of the peroxisome biogenesis disorders. The demonstration that human homologues
      of yeast PAS genes exist and that mutations in these genes cause peroxisome
      biogenesis disorders demonstrates that yeast pas mutants are accurate and useful
      models for the analysis of these diseases.

PMID- 8993571
TI  - Targeted disruption of the peroxisomal fatty acyl-CoA oxidase gene: generation of
      a mouse model of pseudoneonatal adrenoleukodystrophy.

PMID- 8993572
TI  - Increased liver-specific expression of catalase in transgenic mice.

PMID- 8993573
TI  - Mechanism-based risk assessment of peroxisome proliferating rodent
      hepatocarcinogens.

PMID- 8993574
TI  - Hepatocarcinogenesis of peroxisome proliferators.

PMID- 8993575
TI  - Non-genotoxic hepatocarcinogenesis: suppression of apoptosis by peroxisome
      proliferators.

PMID- 8993576
TI  - Mammalian peroxisomes: metabolism of oxygen and reactive oxygen species.

PMID- 8993578
TI  - Regulatory implications: U.S. Environmental Protection Agency.

PMID- 8993577
TI  - Peroxisome proliferators: species differences in response of primary hepatocyte
      cultures.

PMID- 8993579
TI  - Regulatory implications of peroxisome proliferation: an industrial perspective.

PMID- 8993580
TI  - Import of microinjected proteins bearing the SKL peroxisomal targeting sequence
      into the peroxisomes of a human fibroblast cell line: evidence that virtually all
      peroxisomes are import-competent.

PMID- 8993581
TI  - Context dependency of the PTS1 motif in human alanine: glyoxylate
      aminotransferase 1.

PMID- 8993582
TI  - Peb1p (Pas7p) is an intra-peroxisomal receptor for the N-terminal, type 2,
      peroxisomal targeting signal of thiolase.

PMID- 8993583
TI  - Cloning of peroxisome assembly factor-2.

PMID- 8993584
TI  - A new strategy for isolating genes expressing proteins involved in the import of
      peroxisomal proteins.

PMID- 8993585
TI  - Identification of yeast peroxisomal membrane ghosts.

PMID- 8993587
TI  - Microtubule-mediated peroxisomal saltations.

PMID- 8993586
TI  - Sorting of the 70-kDa peroxisomal membrane protein into rat liver peroxisomes in
      vitro.

PMID- 8993588
TI  - The importance of microtubules in determination of shape and intracellular
      distribution of peroxisomes.

PMID- 8993589
TI  - Further characterization of the human peroxisomal C-terminal targeting signal
      protein import receptor.

PMID- 8993590
TI  - Mammalian peroxisomal acyl-CoA oxidases. I. Molecular characterization of rat
      pristanoyl-CoA oxidase.

PMID- 8993591
TI  - Mammalian peroxisomal acyl-CoA oxidases. II. Molecular characterization of rat
      trihydroxycoprostanoyl-CoA oxidase.

PMID- 8993592
TI  - Mammalian peroxisomal acyl-CoA oxidases. III. Molecular characterization of human
      branched chain fatty acyl-CoA oxidase.

PMID- 8993593
TI  - Substrate stereospecificities of rat liver peroxisomal 3-hydroxyacyl-CoA
      dehydrogenases.

PMID- 8993594
TI  - Alpha-oxidation in intact and permeabilized rat hepatocytes.

PMID- 8993595
TI  - Transcriptional regulation of peroxisomal glyoxylate cycle enzymes of an n-alkane
      assimilating yeast, Candida tropicalis.

PMID- 8993596
TI  - Yeast homologue of nonspecific lipid-transfer protein (sterol carrier protein 2)
      may be a stress protein in peroxisomes.

PMID- 8993597
TI  - Peroxisomes contain an enzyme with 17 beta-estradiol dehydrogenase, fatty acid
      hydratase/dehydrogenase, and sterol carrier activity.

PMID- 8993598
TI  - Immunomagnetic isolation of peroxisomes.

PMID- 8993599
TI  - Competition studies of bovine liver catalase, synthetic peptides and artificial
      conjugates for luciferase import in a semipermeabilized cell system.

PMID- 8993600
TI  - Analysis of the essential sequence elements in the peroxisome proliferator
      responsive enhancer of rat acyl-CoA oxidase gene.

PMID- 8993601
TI  - Studies on the role of PPAR in the fibrate-modulated gene expression of
      apolipoprotein A-I, plasminogen activator inhibitor 1, and fibrinogen in primary
      hepatocyte cultures from cynomolgus monkey.

PMID- 8993602
TI  - Structural requirements of chiral clofibric acid analogs for activation of the
      rat peroxisome proliferator-activated receptor alpha.

PMID- 8993603
TI  - Toxicological evaluation of peroxisome proliferators. Further cellular and
      molecular aspects.

PMID- 8993605
TI  - Metabolic requirements for the hepatocellular proliferation induced by peroxisome
      proliferators. Role of coenzyme A.

PMID- 8993604
TI  - Role of eicosanoid metabolism in carcinogenesis by peroxisome proliferators.

PMID- 8993606
TI  - In vivo expression of rat hepatic peroxisomal proteins. Effects of depletion and
      transient restoration of vitamin A reserves.

PMID- 8993607
TI  - Hypolipidemic effect of peroxisome proliferators. Transcriptional suppression of
      apolipoprotein C-III.

PMID- 8993608
TI  - Synergistic activation of the hydratase but not the ApoA1 gene by gemfibrozil and
      retinoids.

PMID- 8993609
TI  - Nonradioactive in situ hybridization for detection of mRNAs of peroxisomal
      enzymes in rat liver.

PMID- 8993610
TI  - Characterization of a cDNA library enriched for a novel peroxisomal gene.

PMID- 8993611
TI  - Pretreatment with peroxisome proliferators protects mice against some but not all
      hepatotoxins.

PMID- 8993612
TI  - Peroxisome proliferators induce high levels of DNA synthesis in primary cultures
      of rat hepatocytes.

PMID- 8993613
TI  - Long survival in a case of peroxisomal biogenesis disorder with peroxisome
      mosaicism in the liver.

PMID- 8993615
TI  - Impaired cholesterol synthesis rate in fibroblasts and reduced cellular uptake of
      LDLs derived from peroxisome-deficient patients cause cellular cholesterol
      deficiency in peroxisome-deficient fibroblasts.

PMID- 8993614
TI  - Biochemical findings in a series of Australian patients with isolated defects in
      peroxisomal beta-oxidation.

PMID- 8993616
TI  - Mutational analysis of an X-linked adrenoleukodystrophy (ALD) patient with
      detectable ALD protein.

PMID- 8993617
TI  - The role of dimerization of alanine:glyoxylate aminotransferase 1 in its
      peroxisomal and mitochondrial import.

PMID- 8993618
TI  - Identification of glucuronide-conjugated hydroxylated fatty acids in the urine of
      children with generalized peroxisomal disorder.

PMID- 8993619
TI  - An S. cerevisiae peroxisomal transporter, orthologous to the human
      adrenoleukodystrophy protein, appears to be a heterodimer of two half ABC
      transporters: Pxa1p and Pxa2p.

PMID- 8993620
TI  - The Pichia pastoris PER6 gene encodes the yeast homologue of human PAF-1.

PMID- 8993621
TI  - Targeting of human catalase to peroxisomes is dependent upon a novel C-terminal
      peroxisomal targeting sequence.

PMID- 8993622
TI  - Truncational analysis of rat urate oxidase in insect cells.

PMID- 8993623
TI  - Mutational analysis of the putative copper-binding site of rat urate oxidase.

PMID- 8993625
TI  - Amphibian catalase: cloning, tissue distribution, and peroxisomal localization.

PMID- 8993624
TI  - Stable expression of peroxisomal fatty acyl-CoA oxidase in vitro.

PMID- 8993626
TI  - Morphometric study of specific heart granules in the grey seal (Halichoerus
      grypus).
AB  - Specific heart granules in the grey seal, Halichoerus grypus, a marine mammal,
      were studied and compared with those in the Wistar rat by ultrastructural
      morphometry. There is extreme paucity of these granules in atrial cells of the
      seal, even in the region of the Golgi apparatus, compared with those in the rat.
      By numerical concentration, granules in the seal are 23 times fewer in number
      than in the rat. They are also fewer in number than in bats and hamsters for
      which data is available. The mean (+/-SEM) diameter of heart granules in the seal
      is significantly less (188 +/- 5.3 nm) than that of the rat (226 +/- 4.6 nm).
      These observations, the first in a marine mammal, are of interest in relation to
      the need for conservation of water and electrolytes in pennipids.

PMID- 8993627
TI  - Distribution of alpha- and beta-subunits of glycoprotein hormones in
      thyrogonadotroph in the anterior pituitary cells of the musk shrew (Suncus
      murinus).
AB  - In order to examine the distribution pattern of alpha- and beta-subunits of
      glycoprotein hormones in small and large granules in the thyrogonadotrophs of the
      musk shrew, we used an antiserum against a synthesized peptide consisting of the
      sequence 37-53 of the rat alpha-subunit, which is highly conservative among
      several mammalian species, and also antisera to LH beta, FSH beta and TSH beta.
      Both alpha- and LH beta-subunits were colocalized in what appeared at the light
      microscopic level to be the same cells, and the population ratio of alpha- and LH
      beta-subunit immuno-reactive cells was almost equal within each group of animals.
      In addition, we also demonstrated thyrogonadotrophs in the infant musk shrew as
      well as in the adult. Concerning small and large granules in thyrogonadotrophs of
      the musk shrew, we could observed small granules immunoreactive for only the
      alpha-subunit, for the LH beta-subunit and for both the alpha- and LH beta
      subunits; while only the LH beta-subunit was observed in the large granules and
      the alpha-subunit was absent. Consequently, we propose that the large granules
      observed in the thyrogonadotrophs of the musk shrew may be storage sites for beta
      subunits and are not secretory-type granules.

PMID- 8993629
TI  - Mandibular molar teeth and the development of mastication in the miniature pig
      (Sus scrofa).
AB  - The only components of the orofacial complex that are fully developed as soon as
      they establish function are the occlusal surfaces of teeth. It is usually assumed
      that the occlusal surface of the molar teeth influences the orientation of the
      power stroke in spite of the fact that the data supporting this claim are
      lacking. The purpose of this longitudinal study was therefore to determine
      whether or not this hypothetical form-function relationship existed during
      development and whether or not it was related to growth. Serial dorsoventral and
      lateral radiography, and dorsoventral cineradiography were performed during
      natural feeding of 5 Hanford miniature pigs (Sus scrofa) of both genders between
      their 8th and 18th weeks. Sequences of power strokes were analyzed frame by frame
      and compared between sessions, and related to the position of the fourth primary
      mandibular molar (dm4). The changes in direction of the power stroke and in
      position of the dm4 relative to the midline were subsequently related to growth.
      The results of this study indicate that changes in orientation of the power
      stroke, though significant only on the balancing side, occur independently of the
      repositioning working and balancing side mandibular molars, as well as of
      skeletal growth. The null hypothesis that the mandibular primary molars influence
      the transverse orientation of the power stroke during growth is therefore
      refuted.

PMID- 8993630
TI  - Histomorphology of the peritendinous tissue of the phalangeal extensor apparatus.
AB  - The phalangeal extensor tendon is surrounded and fixed by connective tissue
      showing differently extended expansions of its intercellular spaces. This
      connective tissue runs in horizontal lamellae and forms connective tissue spaces
      around the dorsal extensor apparatus. The clinical importance of the connective
      tissue spaces is in the formation of gliding spaces and the diffusion of
      phlegmonas or purulent infection processes. The morphological differentiation of
      the cellular and intercellular elements of the dorsal connective tissue lamellae
      shows that the peritendinous gliding spaces around the dorsal aponeurosis are
      bordered by synovia-like cellular and noncellular structures. Besides mast cells
      and histiocytes many cells are seen that show all signs of activated fibroblasts.
      They form small groups of cells. These cells produce a mucoid dense bordering
      lamella that is opposite to the collagenous fibers of the dorsal aponeurosis. The
      intercellular matrix has importance both in fixing and mobilizing the phalangeal
      extensor tendons in the sheathless parts of the phalangeal extensor tendon.

PMID- 8993628
TI  - Morphometry of pineal synaptic ribbon profile numbers after cytochalasin D
      treatment.
AB  - Synaptic ribbons (SRs) are electron-dense, plate-shaped synaptic organelles, to
      which electron-lucent synaptic vesicles (SVs) are attached by tiny stalks. In the
      mammalian pineal gland SRs are dynamic organelles, waxing and warning in number
      under different physiological and experimental conditions. The way in which SRs
      are formed, or catabolized, is not known. Since it has been suggested that actin
      may be part of SRs, in the present study the effect of the actin-disrupting drug
      cytochalasin D (CD, 1 microgram/ml, for 4 h) was examined in cultured guinea pig
      and rat pineal glands. The glands were preincubated for 48 h so that intra-pineal
      sympathetic nerve fibres degenerate and no longer release noradrenaline which may
      distort the results. CD had no effect on SR profile numbers in guinea pigs, but
      decreased them in rats (p > 0.05). The nonsignificant depressive effect of CD in
      rats was verified in a second experiment. To clarify the issue, acutely cultured
      rat pineal glands were treated with CD for 4 h, without effect. The results taken
      together suggest to us that CD has no major effect on pineal SR profile numbers,
      but that in rats preincubation for 48 h makes them vulnerable to catabolic
      processes. In all the experiments, the electron-dense plate of the SRs was
      qualitatively unaffected. However, the SVs were often larger and more irregular
      in shape and the stalks linking the SVs with the SRs were less frequently seen in
      CD-treated glands. In guinea pig pineals, in which SRs frequently lie in groups
      and parallel to each other, neither the distance between neighboring SRs nor the
      thickness of individual SRs were affected by CD. It is concluded that actin is
      not a major component of the SRs and the connecting stalks.

PMID- 8993631
TI  - Morphometric investigations of the connections between the posterior C-1 root and
      the accessory nerve in the human cranial cervical region.
AB  - The anastomosis of the spinal section of the accessory nerve and the posterior C
      1 root was examined in eight human corpses at the light-microscopical level by
      image analysis. The numbers of nerve fibers caudal and cranial to the anastomosis
      were compared. The morphometric data suggest that somatic efferent fibers of the
      spinal accessory nerve extend to proprioceptors in the sternocleido-mastoideus
      and trapezius muscles.

PMID- 8993632
TI  - Anatomical relationship between vagal afferent fibers and CCK-immunoreactive
      entero-endocrine cells in the rat small intestinal mucosa.
AB  - There is evidence for a pathway involving small intestinal CCK-producing entero
      endocrine cells and visceral afferent nerve fibers in signaling the effect of
      luminal nutrients on gastrointestinal and food intake regulation. In order to
      investigate the type of anatomical apposition that exists between CCK cells and
      vagal afferents, CCK immunocytochemistry was performed on tissue from rats whose
      vagal afferent fibers to the abdomen had previously been labeled in vivo by
      injecting the fluorescent carbocyanine dye DiI into the nodose ganglia. CCK
      immunoreactive (CCK-IR) cells were more abundant than vagal afferent fibers, but
      both were present throughout the small intestine as well as in crypts and villi.
      Few CCK-IR cells were in close (< 5 microns) anatomical contact with vagal
      afferent axons, and the latter did not produce suspicious terminal
      specializations near CCK-IR cells. Most labeled vagal afferent axons, which
      distributed strictly within the crypt and villous lamina propria, were at
      distances of tens to hundreds of microns to the nearest CCK-IR cell. These
      findings strongly support the idea that CCK released from entero-endocrine cells
      acts on vagal sensory fibers in a paracrine fashion, but do not rule out the
      presence of a few very close, neurocrine-like contacts or a humoral mode of
      action. Possible implications of such an arrangement on CCK-mediated satiety are
      discussed.

PMID- 8993633
TI  - An anatomical analysis of the relationships between the intercostal nerves and
      the thoracic and abdominal muscles in man. I. Ramification of the intercostal
      nerves.
AB  - Minute dissection was performed on the ventral primary rami of the first thoracic
      to first lumbar nerves in two halves of an adult male cadaver in order to
      determine points of origins of muscular branches from the intercostal nerves.
      Generally, the muscular branches originated independently, but the branches
      supplying the intercostalis intimus and internus tended to originate as a common
      trunk. The muscular branching patterns were compiled in an illustration, and
      based on these patterns the serial homology of the thoracic and abdominal muscles
      was proposed. Although the obliquus externus abdominis has been thought to
      correspond to the intercostales externi, from these innervation findings it
      appears to correspond to the intercostales interni. Further, the quadratus
      lumborum seems homologous to the intercostales externi.

PMID- 8993634
TI  - An anatomical analysis of the relationships between the intercostal nerves and
      the thoracic and abdominal muscles in man. II. Detailed analysis of innervation
      of the three lateral abdominal muscles.
AB  - Minute dissection was performed in one male adult cadaver in order to elucidate
      the detailed distribution of muscular branches of intercostal nerves within the
      lateral abdominal muscles as well as the segmental relationships. In the obliquus
      internus and transversus abdominis, as well as in the upper half of the obliquus
      externus, each muscle fascicle receives the nerve of the corresponding segmental
      attachment to the rib. On the other hand, in the lower half, the obliquus
      externus abdominis receives a twig from the lower adjacent segmental nerve,
      because within the muscle the corresponding segmental nerve first runs
      horizontally and enters the upper adjacent fascicle before descending obliquely,
      parallel to the fiber direction.

PMID- 8993635
TI  - Abnormality of the labyrinthine artery and its topographical relation to the
      abducent nerve.
AB  - A case of duplication of the labyrinthine artery arising from the basilar artery
      is described. The more slender branch takes a dorsal course and penetrates the
      abducent nerve in its uppermost fibres, while the thicker branch passes by the
      nerve on the ventral side. The two branches of the labyrinthine artery run
      separately to the internal auditory meatus. This variant was found only in one
      brain and only on the left side. The clinical relevance of this finding is
      discussed.

PMID- 8993669
TI  - In vivo dose-response characteristics of endothelin-1: studies on rat saphenous
      vein.
AB  - Microangiometric studies were made in vivo on rat saphenous vein to obtain dose
      response contraction curves with endothelin-1. During superfusion of the drug,
      threshold concentrations were found to be in the range of 4 x 10(-11) -4 x 10(
      10) moles/lit, maximal concentrations were about 4 x 10(-8) moles/lit. These
      values are close to published in vitro threshold values. During intravascular
      administration of the drug contraction could be observed in response to a dose as
      small as 4.37 femtomoles/s. The data presented show that characteristic dose
      response curves resembling those found in vitro can be recorded in vivo with
      endothelin on appropriate vascular preparata. The rat in situ saphenous vein
      microangiometric technic can be used for delicate pharmacologic examination of
      venoactive substances in vivo.

PMID- 8993670
TI  - Comparison of the vasodilatory effects of bradykinin in isolated dog renal
      arteries and in buffer-perfused dog kidneys.
AB  - This study was undertaken to investigate the role of nitric oxide (NO),
      cyclooxygenase products and bradykinin (Bk) receptors in the Bk evoked responses
      of canine renal arteries and perfused kidneys. Rings of isolated canine renal
      arteries were mounted in organ chambers for measurement of isometric force. The
      isolated canine kidneys were perfused with Krebs-solution (constant flow) and the
      perfusion pressure was continuously recorded. The influence of the cyclooxygenase
      inhibitor indomethacin and the nitric oxide (NO) synthase inhibitor N omega-nitro
      L-arginin (L-NOARG) on the vasocontractile responses to phenylephrine (PE) were
      examined in both preparations. Furthermore, the effects of Bk on the tone of
      canine isolated renal arteries and on the vasopressor responses of isolated
      buffer-perfused kidneys of dogs were tested in the absence and presence of enzyme
      inhibitors and the B2 kinin receptor antagonist HOE-140. It was found that
      indomethacin enhanced the contractile responses of large renal arteries to PE by
      77 +/- 10%. In intact artery rings L-NOARG (0.1 mM) caused an additional
      potentiation of the PE-induced contractions in the presence of indomethacin (from
      11.5 +/- 1.2 mN to 21.6 +/- 1.7 mN). However, L-NOARG failed to affect
      contractile responses to PE in endothelium-denuded rings. Bk produced a
      concentration-dependent relaxation of the precontracted endothelium-intact renal
      arteries. The IC50 value for Bk was 11.2 +/- 3.7 nM. The relaxant activity of the
      peptide in renal artery rings was not affected by indomethacin (3 microM).
      However, in the presence of L-NOARG a significantly higher concentration (IC50 =
      860 +/- 300 nM) of Bk was required to relax renal arteries. The Bk receptor
      antagonist HOE-140 (10 nM for 40 min) attenuated the relaxant effect of Bk in
      renal artery rings (from an IC50 of 14.2 +/- 2.5 nM to 216 +/- 37 nM).
      Indomethacin (3 microM for 20 min) did not significantly alter the arteriolar
      vasoconstriction (from 45 +/- 4 mm Hg to 48 +/- 5 mm Hg, n = 5) evoked by PE. By
      contrast, L-NOARG (0.1 mM) potentiated (from 56 +/- 7 mm Hg to 94 +/- 11 mm Hg)
      the PE-induced vasopressor responses in perfused kidneys. Bk reduced the size of
      the pressor responses at relatively low concentrations (2-60 nM) but the dose
      response curve was flat and the maximum inhibitory effect hardly exceeded 50
      percent. Indomethacin (3 microM) did not modify the inhibitory effect of Bk in
      perfused kidney. In the presence of L-NOARG, Bk depressed the PE induced
      vasopressor effects with a maximum of 18 +/- 20%. Preincubation of the kidney
      preparations with the Bk antagonist HOE 140 (10 nM for 40 min) almost completely
      abolished the inhibitory effect of Bk on the PE induced vasopressor responses.
      The results suggest that the endothelial NO plays a fundamental role in the
      relaxant effect of Bk and considerably modulates vascular reactivity to PE in
      canine renal vasculature. Furthermore, significant difference exists between
      conduit and resistance vessels of dog's kidney in the effect of indomethacin on
      the adrenergic contractions.

PMID- 8993671
TI  - Effect of perinatal triiodothyronine (T3) treatment on thymic glucocorticoid and
      estrogen receptors and uterus estrogen receptors. Receptor selectivity during
      hormonal imprinting.
AB  - Triiodothyronine (T3) treatment at 1, 3 and 5 days after birth significantly
      increased the binding capacity (density) of the thymus glucocorticoid receptor of
      male and female rats in adult age. There was no change in the binding capacity of
      uterine and thymic estrogen receptors. The experiments point to the sensitivity
      of developing hormone receptors and call the attention to the possibility of
      overlap between the members of the steroid receptor superfamily at the perinatal
      critical period. This overlap is not dependent on the structure of the hormone,
      however it is dependent on the structure of receptors and acceptors. The
      difference in the reaction of glucocorticoid and estrogen receptors shows the
      differences in the sensitivity of receptors to false imprinting.

PMID- 8993672
TI  - Effect of neonatal treatment with monoclonal antibody to thyrotropin (TSH)
      receptor on the thyroxin (T4) level and certain parameters of the internal
      genital organs of adult rats.
AB  - Treatment of newborn rats with a single dose of monoclonal antibody to TSH
      receptor, caused permanent changes in the body weight, T4 level, and different
      sexual parameters. There are considerable sex and organ dependent differences in
      the sensitivity. Body weight and physical condition of males deteriorates, while
      the condition of the females is constant. However, T4 level of females
      significantly increases while that of the males does not change. The weight of
      seminal vesicle increases, while ovarian weight decreases. Effect of hCG
      treatment in adult age is inhibited by neonatal antibody (to TSH receptor)
      treatment. The experiment calls the attention to the imprinter effect of
      antibodies in the neonatal critical period, which effect could be manifested on
      the antibody's own (provoked) or foreign (related) receptor.

PMID- 8993673
TI  - Alterations in skeletal muscle microcirculation of head-down tilted rats.
AB  - The head-down tilted whole body suspended (HDT/WBS) rat is recognized as a model
      that reproduces many of the responses seen during exposure to microgravity
      including an increase in systemic blood pressure. Functional alterations of
      microscopic blood vessels (arterioles) in skeletal muscle (cremaster muscle) were
      assessed for their role in the observed elevations of blood pressure associated
      with HDT/WBS. Arteriolar baseline diameters, vasoconstrictor responses to
      norepinephrine and vasodilation to nitroprusside were assessed in control rats,
      rats suspended for 7 or 14 days, and rats allowed to recover for 1 day after 7
      days of HDT/WBS. Using in vivo videomicroscopy, neither baseline diameters nor
      ability to dilate were altered by HDT/WBS. Maximum vasoconstriction to
      norepinephrine was significantly greater in arterioles of hypertensive 14 day
      HDT/WBS rats. This study of the intact microvasculature of skeletal muscle
      reveals an elevated contractility of arterioles to norepinephrine in suspended
      rats, and suggests that an elevated peripheral resistance in skeletal muscle may
      contribute to the increase in blood pressures among animals subjected to HDT/WBS.

PMID- 8993674
TI  - Autologous connective tissue chamber as a tool for introducing active substances
      into the CNS.
AB  - A new method of introducing active substances into the CNS is described. The
      autologous connective tissue chambers were obtained by implantation of a silicone
      tube under the back skin of rats. Subsequently they were filled with fibrine and
      additionally with NGF or submicrosomal fractions from nonpredegenerated and
      predegenerated peripheral nerves. Filled chambers were implanted stereotaxically
      into the injured hippocampus. The neurite outgrowth was examined by means of FITC
      HRP and acetylcholinesterase-method. Implanted connective tissue chambers are
      very useful in getting active substances into the CNS. This method allows to
      avoid inflammatory processes and does not hinder the histological procedures.

PMID- 8993675
TI  - Solcoseryl improves learning and memory in rats.
AB  - Our previous experiments have shown that Solcoseryl (S), a protein-free extract
      of calves' blood stimulates locomotor activity and decreases haloperidol
      catalepsy in rats. In this study the influence of S on acquisition,
      consolidation, and recall of both, conditioned avoidance responses (CARs) and
      passive avoidance behaviour was tested. S at the intraperitoneal (i.p.) dose of
      1.25 ml/kg significantly improved acquisition and at the dose of 1.0 ml/kg recall
      of CARs. In the passive avoidance situation the significant effect on acquisition
      and recall of information was observed after i.p. injection of 1.0 ml/kg of S,
      and on consolidation after 0.75 ml/kg. These data indicate that S may positively
      affect the CNS processes responsible for learning and memory.

PMID- 8993676
TI  - Solcoseryl stimulates behavioural activity of rats.
AB  - The influence of Solcoseryl (S), a protein-free extract of calves' blood given
      intraperitoneally (i.p.) on the behavioural measures of activity of the central
      nervous system of male Wistar rats was examined. The drug (1.0 ml/kg i.p.) given
      60 min before testing the animals in electromagnetic motimeter significantly
      enhanced overall and vertical motility of rats. S at the doses of 0.5, 1.0 and
      2.0 ml/kg did not significantly influence the activity of rats in "open field".
      1.0 ml/kg of S given 15, 45 and 60 min before thiopental (30 mg/kg i.p.) did not
      change the onset and time of sleep following the latter drug, except for the
      significant shortening of the time of sleep of animals injected with S 15 min
      before thiopental. S at the dose of 1.0 ml/kg did not change stereotypies
      produced by apomorphine (2.0 mg/kg i.p.) and amphetamine (6.5 mg/kg i.p.) but
      decreased intensity of haloperidol (1.0 mg/kg i.p.) catalepsy.

PMID- 8993677
TI  - Assessment of a neuropathic factor in HIV-1 associated impotence: penile
      electrodiagnosis.
AB  - The value of bulbocavernosus reflex latency verses nerve conduction velocity of
      the dorsal nerve of penis and penile brachial index was evaluated in 50 impotent
      individuals infected with the human immunodeficiency virus, type 1 (both
      symptomatic and asymptomatic) and in 50 aged matched HIV-1 sero-negative impotent
      men serving as controls. All the subjects were neurologically asymptomatic and
      non demented. Both HIV-1 infected asymptomatic and symptomatic impotent patients
      exhibited a significant decrease (P < 0.0005) in the nerve conduction velocity of
      the dorsal nerve of penis as well as penile branchial index from the controls of
      the same age group. The latency of bulbocavernosus showed no significant
      difference between the groups and was within the normal limits. A non-significant
      association in the study parameters between HIV-1 infected asymptomatic and AIDS
      positive impotent men was also observed. These findings suggest that impotence
      and altered erectile electrodiagnostic responses are likely to be associated with
      an increased frequency to neuropathy in these patients irrespective of their
      disease state.

PMID- 8993678
TI  - Ultrastructural changes in rat Paneth and goblet cells after the administration
      of interferon-alpha.
AB  - Electron microscopic examination was performed to show the effects of interferon
      alpha (IFN-alpha) on Paneth and goblet cells in rat intestines. After the
      administration of IFN-alpha (70,000 IU/kg), many cells of both types were
      depleted of secretory granules and their apical membranes had the deep cavitation
      that accompanies recent compound exocytotic activity. These results may indicate
      the involvement of these cells in the inflammatory reactions via IFN-alpha and
      this model provides a powerful tool to study differential effects of IFN-alpha on
      Paneth and goblet cells.

PMID- 8993679
TI  - Axonal sprouting and epileptogenesis.

PMID- 8993680
TI  - Seizures and the regulation of neurotrophic factor expression: associations with
      structural plasticity in epilepsy.

PMID- 8993681
TI  - Molecular and cellular cascades in seizure-induced neosynapse formation.
AB  - Limbic seizures induce in vulnerable structures, such as the hippocampal complex,
      morphologic changes that may contribute to the development of epilepsy. They
      include neuronal cell death, reactive gliosis, and neosynapse formation. In
      temporal lobe epilepsy patients, cell death develops in Ammon's horn and the
      hilus. This cell death involves both necrotic and apoptotic mechanisms and is
      likely responsible for the initiation of the glial reaction that consists of
      astroglial and macrophage proliferation and hypertrophy. Reactive astrocytes
      acquire the phenotypic properties of type 2 astrocytes and express trophic
      factors (e.g., bFGF), cell adhesion molecules (e.g., NCAM), and substrate
      molecules (e.g., tenascin-C). Seizures induce in the hippocampus a synaptic
      remodeling of mossy fibers. Mossy fiber collaterals innervate granule cell
      dendrites, creating recurrent excitatory circuits. We suggest that collateral
      branches of MF originate under the influence of trophic factors and as a
      consequence of an overproduction of tubulin polymers. In fact, seizures induce a
      transient increased expression of tubulin and microtubule-associated proteins in
      granule cells and mossy fibers. Navigation of mossy fiber growth cones may be
      facilitated by the interaction with astrocytes, which would exert this effect by
      producing and excreting cell adhesion and substrate molecules. In light of the
      results discussed here, one can suggest that in the adult brain, activated
      astrocytes could contribute to the process of axonal outgrowth and
      synaptogenesis.

PMID- 8993682
TI  - Neurogenetic approaches to axon sprouting in the hippocampus.

PMID- 8993683
TI  - Axonal growth and neosynaptogenesis in human and experimental hippocampal
      epilepsy.

PMID- 8993684
TI  - Mossy fiber reorganization and its possible physiological consequences in the
      dentate gyrus of epileptic humans.
AB  - It is unlikely that MF reorganization is the cause of epilepsy, but it may affect
      the progression of the disease, i.e., the frequency or severity of seizures. We
      propose that early events, yet undiscovered, lead to an increased likelihood of
      excitability. This hyperexcitability, which initially may not be manifested in
      overt seizures, may erode vulnerable hilar neurons that serve an important
      inhibitory function, as illustrated in Fig. 6-15. As inhibition is lost,
      hyperexcitability reaches the level of clinically manifested seizures that are
      severe enough to lead to substantial loss of hilar neurons. When the loss of
      these cells is sufficiently high, MF reorganization occurs, first to neighboring
      hilar neurons and later to dendrites of granule cells (Fig. 6-15). Thus, the
      functional consequence of MF reorganization may provide a compensatory form of
      inhibition, as well as a circuit for feedback excitation. Although definitive
      evidence indicating that MF reorganization contributes to the acceleration or
      progression of epilepsy is missing, the findings to date are consistent with this
      hypothesis. In the event that reorganization contributes to the epileptic
      condition, treatments that reduce indicators of neuropathology may lead to a
      reduction of seizure frequency and severity. Evidence suggests that
      reorganization in the dentate gyrus may follow the pathways of neuronal processes
      of hilar neurons that have died. Thus, further study of the events that guide MF
      reorganization may hold important clues for developing methods for targeting
      regenerating axons following central nervous system injury.

PMID- 8993685
TI  - Related mechanisms of action of growth factors and antioxidants in apoptosis: an
      overview.

PMID- 8993686
TI  - Neurotrophins and programmed cell death during cerebellar development.

PMID- 8993687
TI  - Retinal ganglion cell anatomy and physiology after section of the optic nerve in
      mice overexpressing bcl-2.

PMID- 8993688
TI  - Neuronal necrosis and apoptosis: two distinct events induced by exposure to
      glutamate or oxidative stress.

PMID- 8993689
TI  - Mechanisms of neuronal degeneration: a final common pathway?

PMID- 8993690
TI  - Gene therapy and the use of stem cells for central nervous system regeneration.

PMID- 8993691
TI  - Potential of neural "stem-like" cells for gene therapy and repair of the
      degenerating central nervous system.

PMID- 8993692
TI  - Neural plasticity as studied in neuronal cell lines.

PMID- 8993693
TI  - Herpes simplex virus-1 plasmid vectors for gene transfer into neurons.

PMID- 8993694
TI  - Herpes simplex virus-based vectors: problems and some solutions.

PMID- 8993695
TI  - Injury-stimulated neurogenesis in sensory systems.
AB  - Injury-induced repair of sensory cells does occur in mammals in the sense that
      partial replacement can transpire in sensory ganglion cells and in visual
      photoreceptors. In the somatosensory system, functional replacement of the
      peripheral processes of sensory cells can occur when the cell body is not
      severely damaged. In the visual system, the outer segments of photoreceptors are
      replaced under physiologic conditions, but complete replacement after injury
      occurs only in cold-blooded animals. In the olfactory system, complete
      replacement of sensory nerve cells has evolved as the means by which animals,
      including mammals, can retain olfactory function with a receptor apparatus that
      is highly vulnerable to injury. In the taste system, the sensory cells are also
      disposable and are completely replaced within less than 2 weeks. In the auditory
      and vestibular systems, replacement is not physiologic and when it does occur,
      appears to be injury-induced.

PMID- 8993696
TI  - Strategies for clinical and experimental interventions for repair and
      regeneration in the inner ear.

PMID- 8993697
TI  - Retinal regeneration: common principles but a diversity of mechanisms.

PMID- 8993698
TI  - Long-term response to nerve injury.

PMID- 8993699
TI  - Long-term changes in spinal motor neurons after injury.

PMID- 8993700
TI  - Strategies and mechanisms of recovery after spinal cord injury.

PMID- 8993701
TI  - Postural orientation, equilibrium, and the spinal cord.
AB  - In summary, adequate control of postural orientation and equilibrium is a
      prerequisite for virtually all skilled motor acts, even those apparently simple
      tasks of standing and walking. In the cat, certain aspects of postural
      orientation appear to be organized at the spinal level. In contrast, postural
      equilibrium is not achieved by spinal circuits in isolation, but seems to require
      input from higher centers. The challenge is to identify those higher centers and
      the means by which they produce appropriate postural reactions for maintaining
      balance. If, indeed, postural equilibrium is a function of descending systems,
      then in the future, the amount of recovery of postural equilibrium after injury
      and/or treatment could provide a quantitative measure of the degree of sparing
      and/or re-establishment of functional connections between higher centers and the
      spinal cord.

PMID- 8993702
TI  - Use-dependent plasticity in spinal stepping and standing.

PMID- 8993703
TI  - Recovery of walking after spinal cord injury.

PMID- 8993704
TI  - Intervention strategies to enhance anatomical plasticity and recovery of function
      after spinal cord injury.
AB  - Taken together, our studies indicate that (a) transplants mediate recovery of
      skilled forelimb movement as well as locomotor activity, (b) combinations of
      interventions may be required to restore reflex, sensory, and locomotor function
      to more normal levels after SCI, and (c) that remodeling of particular pathways
      may contribute to recovery of rather specific aspects of motor function. In
      conclusion, we suggest that it seems unlikely that any single intervention
      strategy will be sufficient to ensure regeneration of damaged pathways and
      recovery of function after SCI. Clearly, work from a number of laboratories
      indicates that the dogma that mature CNS neurons are inherently incapable of
      regeneration of axons after injury is no longer tenable. The issue, rather, is to
      identify and reverse the conditions that limit regeneration after SCI. After SCI,
      a hierarchy of "intervention-strategies" may be required to restore
      suprasegmental control leading to recovery of function. The hierarchy may be both
      temporal and absolute. For example, early interventions (such as the
      administration of methylprednisolone within hours of the injury) may be required
      to interrupt the secondary injury cascade and restrict the extent of damage after
      SCI. At the injury site itself, interventions to minimize the secondary injury
      effects may be followed by interventions to alter the environment at the site of
      injury to provide a terrain conducive to axonal elongation. For example, one
      might envision strategies to downregulate the expression of molecules that limit
      growth and upregulate the expression of those that support growth. Early after
      the injury, axotomized neurons may require neurotrophic support either for their
      survival or to initiate and maintain a cell body response supporting axonal
      elongation. There may be an absolute hierarchy as well. Particular populations of
      neurons may have very specific requirements for regenerative growth. For example,
      the conditions that enhance the regenerative growth of descending motor pathways
      may differ from those required by ascending sensory systems. One may also want to
      design strategies to restrict the plasticity of some pathways (e.g., nociceptive)
      and enhance the growth in other pathways. The demands on the CNS for anatomic
      reorganization after SCI may be far less formidable than one might at first
      imagine. If one assumes that recovery of function will require regenerative
      growth of large numbers of axons over long distances in a point-to-point
      topographically specific fashion, the idea of recovery of function becomes
      daunting. On the other hand, it has been shown in many studies and in many areas
      of the CNS that as little as 10% of a particular pathway can often subserve
      substantial function. Furthermore, regrowth over relatively short distances can
      have major functional consequences. For example, relatively modest changes in the
      level of SCI can have relatively profound effects on the functional consequences
      of injury. This is particularly true in cervical SCI: an individual with a C5/6
      SCI is dramatically more impaired than one with C7/8 injury. One might envision
      relatively short distance growth across the injury site to re-establish
      suprasegmental control. Coupled with strategies to enhance the anatomic and
      functional reorganization of spinal cord circuitry caudal to the level of the
      injury, even modest long distance growth may have sufficient functional impact.
      One might imagine the ability to learn to "use" even modest quantities of novel
      inputs in functionally useful, appropriate ways.

PMID- 8993705
TI  - Electrophysiological investigations of neurotransplant-mediated recovery after
      spinal cord injury.

PMID- 8993706
TI  - Embryonic spinal cord transplants enhance locomotor performance in spinalized
      newborn rats.
AB  - The results of the present experiments demonstrate that fetal spinal cord
      transplants placed into the site of a complete transection in newborn rats permit
      the development of complex patterns of locomotion. These patterns differ in some
      respects from normal, but include weight support, appropriate postural
      adjustment, and coordination between forelimbs and hindlimbs. 5-HT agonists
      administered to transplanted rats can further modify these motor patterns in ways
      that may prove able to enhance locomotion. When placed into lesion cavities in
      adult spinal cord, cells genetically modified to express neurotrophins can
      survive, differentiate, and mimic at least one consequence of fetal transplants,
      rescue of axotomized neurons from retrograde cell death.

PMID- 8993707
TI  - Observations on the pathology of several types of human spinal cord injury, with
      emphasis on the astrocyte response to penetrating injuries.

PMID- 8993708
TI  - Neuropathology of human spinal cord injury.

PMID- 8993709
TI  - Neurological assessment in spinal cord injury.
AB  - Precise and reliable neurologic assessment is a necessary tool for determining
      the extent and pattern of recovery after SCI. Recently agreed upon international
      standards establish a uniform neurologic classification to measure clinical
      outcomes. They are currently in use in three multicenter studies in more than 40
      SCI centers in the United States. The Model System SCI centers report the use of
      these measures, such as impairment grades and neurologic levels, in almost 15,000
      cases over the past 20 years and, more recently, motor scores in 3,500 patients.
      The NASCIS II multicenter trial on methylprednisolone used motor and sensory
      scores as endpoints in close to 500 patients, but have incorporated the
      international standards, which include a disability measure, in NASCIS III. The
      study of ganglioside effectiveness also is using these measures in many patients.
      In more focused studies, neurologic assessment soon after injury can predict
      walking in motor complete injuries based on pin prick sensation, and in motor
      incomplete injuries based on impairment grade and age. Eventual upper extremity
      function can be estimated based on the motor examination within 72 hours of
      injury. Both the motor score and motor level are more reliable in predicting
      upper extremity function than the single sensory level. This presumably reflects
      the greater importance of motor recovery on functional outcome. The proximal
      muscles of the lower extremities caudal to the lesion site recover before distal
      muscles, and this may be mediated by axons descending in the ventral tracts,
      which control primarily proximal rather than distal muscles. These axons may be
      preferentially spared and/or have greater capacity to compensate than those
      present in the lateral columns. In conclusion, standard neurologic assessment in
      SCI is extremely valuable in monitoring recovery in order to prognosticate
      functional outcome, evaluate effectiveness of drug interventions, and provide
      valuable clues to possible underlying mechanisms of recovery. The elucidation of
      these mechanisms will aid in the refinement of current treatments and development
      of new strategies to enhance neurologic recovery and functional outcome.

PMID- 8993710
TI  - Motor control physiology below spinal cord injury: residual volitional control of
      motor units in paretic and paralyzed muscles.
AB  - We have described motor control in people with different degrees of SCI by using
      surface polyelectromyographic recordings during single- and multijoint volitional
      motor tasks. We have shown that neurobiologic conditions of the injured spinal
      cord can be expressed in two main categories: "new anatomy" and "reduced
      anatomy". The evidence for a variety of definite features of motor control
      elicited by volitional effort for the performance of a present or even clinically
      absent motor task suggests that we can benefit from animal experimental
      neurobiologic studies while we are progressing toward the application of this new
      knowledge for the restoration of impaired spinal cord function in humans. Reports
      on the successfully enhanced regenerating capabilities of the axons and improved
      connectivity within neuronal circuits after SCI encourage us to intensify our
      efforts in parallel with studies on the recovery processes found in
      experimentally induced lesions in animals, as well as in accidentally induced SCI
      in humans.

PMID- 8993711
TI  - Modification of urinary bladder function after spinal cord injury.

PMID- 8993712
TI  - Functional recovery: after the regeneration stops.

PMID- 8993713
TI  - Therapeutic approaches to spinal cord injury.

PMID- 8993714
TI  - Maintaining safer sex behaviours in HIV-infected adolescents with haemophilia.
      The Hemophilia Behavioral Evaluative Intervention Project Committee.
AB  - Adolescents with haemophilia comprise 44% of the reported AIDS cases in
      teenagers. Unprotected sexual intercourse among this group increases the risk of
      HIV transmission. Understanding the influences which others may have on the
      sexual behaviour of adolescents with HIV and haemophilia may lead to the
      development of effective risk reduction strategies. An evaluative instrument,
      administered to 307 HIV-infected adolescents with haemophilia, assessed their
      behavioural stage of change (Prochaska & DiClemente), attitudes, beliefs and
      behaviours about safer sex practices. The influence of parents, peers and sexual
      partners on sexual behaviour was compared between (1) those who were sexually
      experienced and (2) and those who were sexually inexperienced. Barriers and
      facilitators to practising safer sex were identified. Although parents influenced
      the sexual behaviour of both groups, this influence was significantly greater in
      the sexually inactive group. Fewer than 20% reported that their peers impacted
      their decisions about sexual behaviour. Eighty-six per cent of the sexually
      active indicated that partners significantly impacted their sexual decisions,
      while 60% of the sexually inactive indicated that future partners would affect
      their decisions about sex. Most participants agreed that disclosure of HIV status
      before intercourse was desirable, but only 31% of the sexually active said they
      told every partner. Fear of rejection or a negative reaction from the partner,
      and lack of communication skills were the greatest barriers to disclosure of HIV
      status and practising safer sex. This study indicates that behavioural
      interventions for both groups should focus on developing communication skills and
      self-efficacy. Interventions should include the key influences for each group-
      parents for the sexually inactive and partners for the sexually active.

PMID- 8993715
TI  - Adolescent sexuality: the gender gap.
AB  - The aim of this paper is to determine gender differences as regards adolescent
      sexuality, in order to improve the adjustment of prevention programmes to boys'
      and girls' specific needs. Data were collected as part of the Swiss Multicentric
      Adolescent Survey on Health. Anonymous questionnaires were distributed in school
      classes among a national representative sample of about 9,300 adolescents (15 to
      20 years old). About 45% of the total sample reported a previous sexual
      experience. Differences between boys and girls were identified by means of
      bivariate and multivariate analyses. A higher proportion of Swiss girls report
      intra-family discussions about sexuality, having had a previous sexual
      experience, having sexual intercourse regularly, having had only one partner, and
      using contraception regularly. A higher proportion of Swiss boys report positive
      attitudes towards condoms and using condoms regularly. Variables independently
      associated with the occurrence of first sexual intercourse before 15 years old
      also show gender differences, notably as regards health behaviours and social
      adjustment. The findings suggest that prevention programmes should emphasize,
      among boys, responsibility in contraception and the need for protection in
      situations of multipartnership, and among girls, a positive attitude towards
      condom use and an increased familiarity with condoms presented both in a
      perspective of contraception and prevention of STDs.

PMID- 8993716
TI  - Sex, drugs and escape: a psychological model of HIV-risk sexual behaviours.
AB  - The lack of an effective HIV vaccine or other biomedical intervention means that
      behavioural change will continue to be critical to the prevention of HIV
      infection. Despite near universal knowledge of HIV and sexual safety, and
      widespread intentions to be safe, rates of unprotected sex and HIV sero
      conversion remain high among gay and bisexual men. Explanatory models that link
      risk-taking and prevention to rational processes such as knowledge, social norms,
      behavioural intentions, or perceived vulnerability to infection, cannot fully
      account for the continued risk behaviours observed in virtually all cohorts of
      gay men. We feel that innovative conceptions of risk and risk prevention are
      needed, that emphasize non-rational, affective processes in risk-taking and
      decision-making. Consistent with recent models from social psychology, we propose
      that for many people sexual risk does not stem from a lack of community norms or
      personal standards, but from a desire to escape cognitive awareness of very
      rigorous norms and standards. Being self-aware of HIV risk arouses anxiety and
      precludes highly-desired activities: fatigue, fatalism, or other negative affect
      over HIV may lead people to 'cognitively disengage' within the sexual situation,
      and not to follow their norms or intentions toward safety. We propose that both
      substance use and the approach of high stimulation or other sexual settings
      facilitates this cognitive disengagement, wherein people enact 'automatic' sexual
      scripts and/or become more responsive to external pressures toward risk. We
      briefly review current psychosocial models of HIV risk behaviour, outline a
      cognitive escape model with particular emphasis on substance use as a behavioural
      risk factor, and discuss implications of an escape model for behavioural
      interventions among gay and bisexual men.

PMID- 8993717
TI  - An assessment of the risks of syphilis and HIV infection among a sample of not-in
      treatment drug users in Houston, Texas.
AB  - The research presented in this paper details the results of an assessment of the
      risk factors associated with having a positive syphilis or HIV serology. The
      study was conducted using a sample of not-in-treatment drug users volunteering to
      participate in an HIV risk reduction intervention. The sample was composed of
      individuals who had injected drugs within 30 days or smoked crack cocaine 48
      hours prior to participation in the study. Study participants were approximately
      75% male and 66% African-American. All participants provided a blood sample to be
      tested for HIV and syphilis. Analysis of risk was conducted using univariate and
      multivariate statistical methods. Multivariate analysis of blood results showed
      that women, African-Americans, and those having a positive blood test for HIV
      were at higher odds of having a positive syphilis test. Analysis also showed that
      being a gay or bisexual male, having a history of drug injection, having less
      than a high-school education, having a history of trading sex for money, being
      African-American, and having a positive blood test for syphilis significantly
      increased the odds of a positive HIV test. Implications for HIV and STD
      prevention are discussed.

PMID- 8993718
TI  - Use of folk healing practices by HIV-infected Hispanics living in the United
      States.
AB  - In the absence of a medical cure for AIDS, HIV-infected individuals may seek
      alternative treatments that are consistent with cultural and social beliefs. This
      paper examines beliefs about, and use of, folk healing practices by HIV-infected
      Hispanics receiving care at an HIV/AIDS clinic in inner-city New Jersey.
      Anonymous individual interviews were conducted with 58 male and 18 female HIV
      infected Hispanics aged 23-55, primarily of Puerto Rican origin (61%) or descent
      (29%). The majority of respondents believed in good and evil spirits (73.7%);
      among the 56 believers, 48% stated that the spirits had a causal role in their
      infection, either alone or in conjunction with the AIDS virus. Two thirds of the
      respondents engaged in folk healing (spiritualism and/or santeria). The main
      desired outcomes of folk healing included physical relief (44%), spiritual relief
      (40%), and protection from evil (26%). A number of respondents (n = 9) stated
      that they hoped to effect a cure by engaging in folk healing. These results
      indicate that health care professionals treating HIV-positive Hispanics should be
      aware of the prevalence of folk beliefs and alternative healing practices in this
      population.

PMID- 8993719
TI  - Self-help and life quality in persons with HIV disease.
AB  - This study examined factors contributing to life quality in persons with HIV
      disease. Selected concepts and statements in a model designed to explain self
      help and life quality in persons with chronic conditions were tested. Eighty
      three persons with a diagnosis of HIV disease (58% with AIDS) completed a
      demographic profile and four instruments to measure dependence for help with
      daily living, enabling skills, self-help and life quality. The instruments had
      been used by researchers testing the Self-Help Model on persons with other
      chronic diseases. Direction and magnitude of the relationships, revealed through
      causal modelling procedures, were consistent with previous tests of the model.
      Diagnosis of AIDS explained 29% of the variance in dependency, but had no
      explanatory value for enabling skill. Enabling skill (beta = 0.32) and dependency
      (beta = -0.49) explained 33% of the variance in self-help. Self-help (beta =
      0.59) explained 34% of the variance in life quality. Results suggest that self
      help is influenced negatively by dependency and positively by enabling skill.
      Enabling skill appears to mediate the negative effect of dependency on self-help
      and can be a target of interventions to improve quality of life in persons with
      HIV disease.

PMID- 8993721
TI  - Are people with HIV in London able to die where they plan?
AB  - Being able to die where you plan is a measure of quality of life near death, in
      that it implies awareness of diagnosis and prognosis, adequate symptom control
      and involvement in decision-making in late-stage HIV disease. This study presents
      trends in place of death for patients attending a large central London HIV centre
      and examines whether patients dying over a 6-month period in 1994 were able to
      die where they planned. Early in the epidemic almost all people with HIV died in
      hospital, but in the late 1980s there was an increase in death at home and in
      hospices. Of people attending this hospital in 1994, 46% died in hospital, 31% at
      home, 20% in hospices and 2% abroad. A total of 59% of deaths were where the
      dying person had planned. Most unplanned deaths were in hospital, two-thirds
      being due to an unexpected deterioration which precluded planning. The rest were
      a mixture of people waiting for discharge to die elsewhere, and people who wished
      to continue active treatment. This pattern of place of death is unlikely to
      change in the near future. It is therefore essential that hospitals can provide
      for the needs of patients dying on acute wards.

PMID- 8993722
TI  - WHO Global AIDS Statistics.

PMID- 8993720
TI  - An overview of HIV prevention in central and eastern Europe.
AB  - HIV and AIDS present a major challenge to the countries of central and eastern
      Europe. The manner in which this is being addressed differs from country to
      country, depending upon historical traditions and prevailing public health
      practices, social values and political priorities. This paper provides an
      overview of HIV prevention policies in six central and east European counties:
      Russia, Romania, Hungary, the Czech Republic, Poland and Lithuania. By homing in
      on particular aspects of these policies, the paper aims to highlight some of the
      more interesting contrasts that exist within this region. The paper concludes
      that, while significant comparisons can be made between the countries, tight
      parallels cannot.

PMID- 8993723
TI  - Scuba diving in individuals with asthma.

PMID- 8993725
TI  - Exercise physiology.
AB  - Muscular exercise presents a significant challenge to the lung and gas exchange
      functions of the respiratory system. The cardiovascular system is thought to be
      the main limit to maximal exercise performance. The increase in ventilation with
      exercise is significant, but only in the elderly and highly fit is the pulmonary
      system a mechanical limit to exercise performance. Although the response in gas
      exchange is not perfect, the PaO2 remains preserved at the level of rest. As the
      oxygen delivery fails to meet the metabolic demand of the working muscle, the
      resultant metabolic acidosis elicits a ventilatory compensation. It is important
      to remember that the hemostatic and integrative nature of these organ systems can
      make treating each component as a discreet element very unrealistic and
      misleading. Muscular exercise remains a superb example of the capacity of the
      ventilatory/gas exchange systems to adapt to stress.

PMID- 8993724
TI  - Exercise-induced asthma: a practical guide to definitions, diagnosis, prevalence,
      and treatment.
AB  - Exercise-induced asthma is defined as an intermittent narrowing of the airways,
      demonstrated by a decrease in some measure of flow, that the patient experiences
      as wheezing, chest tightness, coughing, and difficulty breathing that is
      triggered by exercise. Exercise will trigger asthma in most individuals who have
      chronic asthma, as well as in some who do not otherwise have asthma. Definitive
      diagnosis requires demonstration of a drop in flow rate, typically > or = 13-15%
      for forced expiratory volume in one second (FEV1) and > or = 15-20% for peak
      expiratory flow rate (PEFR), after exercise, associated with symptoms. Prevalence
      data indicate that this disorder is very common in those who participate in
      recreational sports as well as in highly competitive athletes, with at least 12
      15% of unselected athletes having positive exercise challenges. Treatment of
      exercise induced asthma involves use of nonpharmacological measures (such as the
      use of the refractory period after exercise and prewarming air) as well as use of
      medications (beta-agonists, cromolyn, and nedocromil). With treatment, those who
      suffer from exercise-induced asthma may be able to participate and compete at the
      highest levels of performance.

PMID- 8993726
TI  - Leukotrienes: pathophysiologic role and therapeutic potentials in asthma.

PMID- 8993727
TI  - Theophylline revisited.
AB  - For over 50 years, theophylline has been used regularly for the management of
      chronic asthma. However, because of its perceived narrow therapeutic index and
      the fact that it has been considered a weak bronchodilator, the use of
      theophylline therapy has diminished. Furthermore, with the introduction of newer
      pharmacologic agents and recommendations in widely accepted guidelines, both
      nationally and internationally, have further contributed to its decreased use.
      For years, theophylline has not only been considered a bronchodilator, but for
      many clinicians, an agent that could be used to enhance respiratory muscle
      function and mucociliary clearance and act at the level of the central nervous
      system to enhance ventilation. These properties were felt to be potentially
      useful for patients with severe exacerbated asthma. Recent studies have suggested
      that theophylline therapy can play a beneficial role in the management of both
      chronic stable asthma and exacerbated disease treated in the emergency department
      setting. Furthermore, a growing body of evidence suggests that theophylline has
      certain antiinflammatory and immunomodulating properties, even at plasma
      concentration levels below the accepted therapeutic range. If this is true, then
      theophylline may act best as a controller medication in the management of asthma.
      Because of its low cost and its ease of administration, theophylline therapy
      should be revisited and discussed as not only a reliever of bronchospasm, but a
      controller of chronic asthma.

PMID- 8993728
TI  - The role of glucocorticoids in the management of asthma.
AB  - Glucocorticoids (GCs) are a highly effective class of medication used in the
      treatment of airway inflammation associated with chronic asthma. Nevertheless,
      there remain concerns regarding potential adverse effects accompanying the use of
      systemic and high-dose inhaled GC therapy. Recent studies also suggest that there
      is high variability in airway response to GCs. Indeed, the immunopathogenesis of
      a subset of asthmatics poorly responsive to glucocorticoid therapy have been
      studied and may provide new insights into mechanisms by which glucocorticoids act
      in chronic asthma. The current review will examine a number of these issues,
      particularly mechanisms by which GCs act in asthma, the immunology of steroid
      resistance, and adverse effects associated with GC treatment.

PMID- 8993729
TI  - Inhalational therapy in asthma.

PMID- 8993731
TI  - Medical care management.

PMID- 8993730
TI  - The role of outcome studies in allergy and clinical immunology.
AB  - Outcomes research is becoming an integral part of the sweeping changes occurring
      in the U.S. health care system. By developing outcomes monitoring systems in
      allergic disorders, allergists will be able to collect information showing their
      commitment to excellent clinical care, which improves the patient's quality of
      life in a cost-effective way. Outcomes data is also important in determining the
      number of allergists that need to be trained, appropriate therapeutic regimens
      for allergic disorders, evaluating differences in practice styles of allergists
      throughout the country, and in revising practice parameters in allergic
      disorders. Through the Joint Council of Allergy, Asthma, and Immunology, a
      subcommittee on outcomes was formed. This subcommittee awarded a national asthma
      outcomes monitoring project to The Health Institute, New England Medical Center,
      Boston. This project, which will be in three phases, will generate information on
      outcomes of board-certified allergists in asthma care. Another goal of this
      project will be to produce standardized instruments and collection methods, which
      will be made available for use by all allergists to collect their own outcomes
      data.

PMID- 8993749
TI  - Transfer Factor in the Era of AIDS. Proceedings of the Xth International
      Symposium on Transfer Factor. Bologna, Italy, 22-24 June 1995.

PMID- 8993732
TI  - Asthma among the famous. A continuing series.

PMID- 8993750
TI  - Transfer factor--current status and future prospects.
AB  - We have detected new clues to the composition and function of "Transfer Factor"
      using the direct Leucocyte Migration Inhibition (LMI) test as an in vitro assay
      of Dialysates of Leucocyte Extracts (DLE). This approach has revealed two
      opposing antigen-specific activities to be present in the same > 3500 < 12,000 DA
      dialysis fraction - one activity is possessed of Inducer/Helper function (Inducer
      Factor). The opposing activity is possessed of Suppressor function (Suppressor
      Factor). When non-immune leucocyte populations are cultured with Inducer Factor
      they acquire the capacity to respond to specific antigen and inhibition of
      migration occurs. This conversion to reactivity is antigen-specific and dose
      dependent. When immune leucocyte populations are cultured with Suppressor Factor
      their response to specific antigen is blocked and Inhibition of Migration is
      prevented.

PMID- 8993751
TI  - Transfer factor in the age of molecular biology: a review.
AB  - Current data suggests that the transferring of immunologically specific
      information by transfer factor molecules requires interaction with a cell that
      has been genetically programmed to be antigen reactive but at the time of
      interaction is unprimed. Contact with transfer factor molecules would allow a
      naive recipient, on a first encounter with antigen, to make a secondary rather
      than a primary immunological response. Transfer factor molecules for each and
      every antigenic determinant are thus necessary. Transfer factors made from
      animals or humans are capable of transferring antigen specificity across a
      species barrier. Even primitive species have cells from which one can make
      transfer factors. The molecules are, therefore, well conserved and it is
      reasonable to suggest that they are important for normal immunological
      functioning. Proposed mechanisms of action must explain the fact that transfer
      factors obtained from the cells of high responder animals are capable of
      transferring delayed hypersensitivity to low responder animals while the reverse
      is not true. Transfer factor molecules are likely to interact with the variable
      regions of the alpha and/or beta chain of T cell receptors to change their
      avidity and affinity for antigen in a way that otherwise would only occur after
      an encounter with antigen.

PMID- 8993752
TI  - Activities and characteristics of transfer factors.
AB  - This report summarizes three components of our transfer factor research program.
      Several clinical studies have used oral administration of transfer factor
      containing materials. Sceptics have rejected these findings by assuming that the
      acidic and enzymatic environment of the gastrointestinal tract would destroy the
      factors. To further examine this issue, we have conducted dose-response studies
      of the delayed-type hypersensitivity reaction in mice that were given transfer
      factor either by gavage or subcutaneously. There were no difference in the
      responses that were related to the route of administration. We conclude that oral
      route of administration is efficacious and should be used when possible. We have
      also studied the effects of transfer factors on immune responses by recipients.
      The details of this research are presented in the paper by Dr. Alvarez-Thull.
      Briefly, the study showed that recipients of a specific transfer factor responded
      to the antigen for which the factor was specific by secreting gamma-IFN, but no
      other cytokines. The structures of transfer factor molecules are unknown. We have
      developed a process for isolating transfer factors in pure form and we have
      obtained preliminary data concerning amino acid sequences. Our goal is to obtain
      the complete primary structure of several transfer factor molecules.

PMID- 8993753
TI  - AIDS and transfer factor: myths, certainties and realities.
AB  - At the end of the 20th century, the triumph of biology is as indisputable as that
      of physics was at the end of the 19th century, and so is the might of the
      inductive thought. Virtually all diseases have been seemingly conquered and HIV,
      the cause of AIDS, has been fully described ten years after the onset of the
      epidemic. However, the triumph of biological science is far from being complete.
      The toll of several diseases, such as cancer, continues to rise and the
      pathogenesis of AIDS remains elusive. In the realm of inductive science, the
      dominant paradigm can seldom be challenged in a frontal attack, especially when
      it is apparently successful, and only what Kuhn calls "scientific revolutions"
      can overthrow it. Thus, it is hardly surprising that the concept of transfer
      factor is considered with contempt, and the existence of the moiety improbable:
      over forty years after the introduction of the concept, not only its molecular
      structure remains unknown, but also its putative mode of action contravenes
      dogmas of both immunology and molecular biology. And when facts challenge
      established dogmas, be in religion, philosophy or science, they must be
      suppressed. Thus, results of heterodox research become henceforth nisi-i.e.,
      valid unless cause is shown for rescinding them, because they challenge the
      prevalent paradigm. However, when observations pertain to lethal disorders, their
      suppression in the name of dogmas may become criminal. Because of the failure of
      medical science to manage the AIDS pandemic, transfer factor, which has been
      successfully used for treating or preventing viral infections, may today overcome
      a priori prejudice and rejection more swiftly. In science, as in life,
      certainties always end up by dying, and Copernicus' vision by replacing that of
      Ptolemy.

PMID- 8993754
TI  - Rationale and clinical results of using leucocyte-derived immunosupportive
      therapies in HIV disease.
AB  - Leucocyte dialysates contain a number of substances which exert important effects
      on human cell-mediated immunity. In this report, we describe several properties
      of a designated subfraction, IMREGR-1, which is obtained by a second dialysis
      against a membrane having a 3500 m.w. cutoff. These include the ability to
      augment and accelerate reactions of delayed hypersensitivity against antigens to
      which the test subject has been previously sensitized, and the ability to enhance
      the expression in vitro on CD4 lymphocytes of the p55 subunit of the receptor for
      Interleukin-2. We also report our observation that in a patient with advanced HIV
      disease whose lymphocytes had lost there ability to properly express the IL-2
      receptor, treatment with IMREGR-1 over a period of months restored the expression
      of the IL-2 receptor on the patient's CD4+ lymphocytes towards normal.

PMID- 8993755
TI  - Inhibition of in vitro HIV infection by dialysable leucocyte extracts.
AB  - Dialysable Leucocyte Extract (DLE) is a low molecular weight dialysable material
      of disrupted peripheral human leucocytes with widespread effects on the immune
      system. We described the in vitro anti-HIV activity of DLE as well as its three
      chromatographic fractions (Fa, Fb and Fc). To determine the levels of inhibition
      on HIV replication by DLE we infected MT-4 cell cultures, using the Bru viral
      isolate at 0.05, 0.1, 0.5 and 1 m.o.i. Previously, MT-4 cells cultures were
      treated with DLE or fractions at non-toxic concentrations. Reverse transcriptase
      (RT) activity and p24 antigen were evaluated in culture supernatants at seven
      days postinfection. No effect was observed when MT-4 cells were incubated with
      DLE for 3 h. Whereas inhibition of HIV production was observed when MT-4 cells
      were pre-treated for a longer period of time. DLE inhibited p24 production and RT
      activity more than 50% at 0.1 m.o.i. More than 80% of inhibition was observed for
      all doses of DLE tested at 0.05 m.o.i. Higher viral doses (m.o.i. 0.5 and 1) were
      used to assess the antiviral activity of DLE fractions. Fraction Fb inhibits
      viral production more than 80%. Otherwise, fractions Fa and Fc did not show
      inhibitory effect for any viral dose used. These results indicate that DLE is
      able to modulate cell susceptibility to viral infection in vitro.

PMID- 8993756
TI  - Preliminary observations using HIV-specific transfer factor in AIDS.
AB  - Twenty five HIV-1-infected patients, at various stages (CDC II, III and IV) were
      treated orally with HIV-1-specific transfer factor (TF) for periods varying from
      60 to 1870 days. All patients were receiving antiviral treatments in association
      with TF. The number of lymphocytes, CD4 and CD8 subsets were followed and showed
      no statistically significant variations. In 11/25 patients the number of
      lymphocytes increased, whilst in 11/25 decreased; similarly an increase of the
      CD4 lymphocytes was observed in 11/25 patients and of the CD8 lymphocytes in
      15/25. Clinical improvement or a stabilized clinical condition was noticed in
      20/25 patients, whilst a deterioration was seen in 5/25. In 12/14 anergic
      patients, daily TF administration restored delayed type hypersensitivity to
      recall antigens within 60 days. These preliminary observations suggest that oral
      HIV-specific TF administration, in association with antiviral drugs, is well
      tolerated and seems beneficial to AIDS patients, thus warranting further
      investigation.

PMID- 8993757
TI  - Preliminary results in HIV-1-infected patients treated with transfer factor (TF)
      and zidovudine (ZDV).
AB  - The efficiency of HIV-1 specific transfer factor (TF) administration, combined
      with Zidovudine (ZDV), in asymptomatic persistent generalised lymphadenopaty, or
      AIDS related complex (ARC) patients was evaluated. Twenty patients were randomly
      assigned to receive only ZDV (1st group) or ZDV together with HIV-1-specific TF
      (2nd group). HIV-1-specific TF was administered orally at 2 x 10(7) cell
      equivalent daily for 15 days, and thereafter once a week for up to 6 months.
      There were no significant differences between the two groups in clinical
      evolution, red blood cells, haemoglobin, lymphocytes, CD20 subset, transaminases,
      beta-2-microglobulin, p24 antigen. White blood cells, CD8 lymphocytes as well as
      IL-2 levels increased in the second group, while the CD4 subset increased in the
      first group. The combination treatment with ZDV and TF appeared to be safe and
      well tolerated. Furthermore, levels of serum cytokines were investigated in 10
      patients (8 asymptomatic and 2 ARC) treated with ZDV, and compared with 5
      patients of the 2nd group (3 asymptomatic and 2 ARC) treated with ZDV plus HIV-1
      specific TF. Peripheral lymphocytes, CD4, CD8 subsets, IL-2, TNF alpha, IL-6, p24
      antigen, IL-2 soluble lymphocyte receptors (sR), CD4sR, CD8sR and beta-2
      microglobulin were evaluated at the baseline and at the 3rd month. The CD4 subset
      was not significantly different in the two groups, whilst IL-2 increased in the
      2nd group receiving ZDV plus TF, suggesting an activation of the Th1 secretion
      pattern.

PMID- 8993758
TI  - Profiles of cytokine production in recipients of transfer factors.
AB  - Transfer factors (TF) are proteins that transfer the ability to express cell
      mediated immunity from immune donors to non-immune recipients. The mechanisms of
      these effects have not been defined. The experiments described in this report
      were undertaken to test the hypothesis that a mechanism through which the
      beneficial effects of TF are expressed in clinical situation is through
      "education" of the immune system to produce certain cytokines in response to
      antigenic stimulation. BALB/c mice were sensitized to Herpes simplexvirus (HSV)
      either by sublethal systemic or cutaneous infections by administration of a HSV
      specific TF. One week later their spleen cells were collected and single cell
      suspensions were stimulated in vitro with irradiated HSV or concanavalin. A
      Culture supernatants were collected and assayed for content of IL-2, IL-4, IL-10
      and IFN-g. Spleen cells from infected mice responded to concanavalin A and to HSV
      by secreting large amounts of IL-2 and IFN-g, modest amounts of IL-10, and no IL
      4. Transfer factor recipients produced similar cytokine profiles in response to
      concavalin A. These mice, however, responded to HSV by secreting IFN-g, but no IL
      2. Thus, TF treatment selectively affects cytokine production in response to
      antigenic stimulation.

PMID- 8993759
TI  - Efficacy of transfer factor in treating patients with recurrent ocular herpes
      infections.
AB  - Recurrent ocular herpes is an insoluble problem for the clinician. As cellular
      immunity plays an important role in controlling herpes relapses, and other
      studies have shown the efficacy of HSV-specific transfer factor (TF) for the
      treatment of herpes patients, an open clinical trial was undertaken in 134
      patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from recurrent
      ocular herpetic infections. The mean duration of the treatment was 358 days, and
      the entire follow-up period 189,121 before, and 64,062 days after TF treatment.
      The cell-mediated immune response to the viral antigens, evaluated by the
      lymphocyte stimulation test (LST) and the leucocyte migration test (LMT) (P <
      0.001), was significantly increased by the TF treatment. The total number of
      relapses was decreased significantly during/after TF treatment, dropping from 832
      before, to 89 after treatment, whereas the cumulative relapse index (RI) dropped,
      during the same period, from 13.2 to 4.17 (P < 0.0001). No side effects were
      observed. It is concluded that patients with relapsing ocular herpes can benefit
      from treatment with HSV-specific TF.

PMID- 8993760
TI  - Orally administered HSV-specific transfer factor (TF) prevents genital or labial
      herpes relapses.
AB  - Forty-four patients suffering from genital (22) and labial (22) herpes were
      orally treated with HSV-1/2-specific transfer factor (TF). TF was obtained by in
      vitro replication of a HSV-1/2-specific bovine dialysable lymphocyte extract.
      Treatment was administered bi-weekly the first 2 weeks, and then weekly for 6
      months, most patients received 2-3 courses. The total observation period for all
      patients before treatment was 26,660 days, with 544 relapses, and a relapse index
      of 61.2, whereas the cumulative observation period during and after treatment was
      16,945 days, with a total of 121 relapsing episodes and a cumulative RI of 21.4
      (P < 0.0001). Results were equally significant when the 2 groups of patients
      (labial and genital) were considered separately. These observations confirm
      previous results obtained with bovine HSV-specific TF, and warrant further
      studies to establish HSV-specific TF as a choice of treatment for preventing
      herpes recurrences.

PMID- 8993761
TI  - Effect of anti-herpes specific transfer factor.
AB  - Using a blood cell separator, lymphocytes were collected from otherwise healthy
      convalescents suffering from herpetic infections. A specific anti-herpes
      dialysate (AH-DLE) was prepared from the lymphocytes, using standard procedures.
      Patients with recurrent herpetic infections were treated with a single dose of
      the dialysate, at the initial signs of herpetic infection (group A), with two
      doses (group B) or with three doses (group C). A total number of 37 patients (29
      women, 8 men, age range 15-73 years) were treated. No improvement was observed in
      7 patients (18.9%), whilst 7 patients did not manifest any exacerbation of their
      herpetic infection in the course of the one-year follow-up. The remaining 62.2%
      of the patients showed a marked improvement: decrease of the frequency and/or
      duration or relapses. Before AH-DLE administration, the mean number of herpes
      relapses in this group of patients was 12 p.a.. After therapy, the number of
      relapses decreased to 3.5 p.a.. No statistically significant difference was
      observed between groups A and B. The least favourable results were registered in
      group C. However, this group included 6 female patients extremely resistant to
      the previously therapeutic attempts, including inosiplex, non-specific DLE or
      acyclovir. Thus, even in this group, the therapy was successful in 50% of the
      patients.

PMID- 8993762
TI  - The use of transfer factors in chronic fatigue syndrome: prospects and problems.
AB  - Chronic fatigue syndrome (CFS) is a heterogeneous disorder characterized by
      severe prolonged unexplained fatigue and a variety of associated symptoms such as
      arthralgias, myalgias, cognitive dysfunction, and severe sleep disturbances. Many
      patients initially present with an acute onset of apparent infectious origin with
      either an upper respiratory or gastrointestinal illness, fever, chills, tender
      lymphadenopathy, and malaise suggestive of a flu-like illness. In some cases,
      specific viral infections can be identified at the outset, particularly herpes
      viruses such as Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6), and
      cytomegalovirus (CMV). Transfer factors (TF) with specific activity against these
      herpes viruses has been documented. With some studies suggesting that persistent
      viral activity may play a role in perpetuation of CFS symptoms, there appears to
      be a rationale for the use of TF in patients with CFS and recent reports have
      suggested that transfer factor may play a beneficial role in this disorder. This
      report focuses on the heterogeneity of CFS, the necessity for randomized coded
      studies, the importance of patient selection and sub-classification in clinical
      trials, and the need to utilize specific end-points for determining efficacy of
      treatment.

PMID- 8993763
TI  - Use of anti HHV-6 transfer factor for the treatment of two patients with chronic
      fatigue syndrome (CFS). Two case reports.
AB  - Specific Human Herpes virus-6 (HHV-6) transfer factor (TF) preparation,
      administered to two chronic fatigue syndrome patients, inhibited the HHV-6
      infection. Prior to treatment, both patients exhibited an activated HHV-6
      infection. TF treatment significantly improved the clinical manifestations of CFS
      in one patient who resumed normal duties within weeks, whereas no clinical
      improvement was observed in the second patient. It is concluded that HHV-6
      specific TF may be of significant value in controlling HHV-6 infection and
      related illnesses.

PMID- 8993764
TI  - Lessons from a pilot study of transfer factor in chronic fatigue syndrome.
AB  - Transfer Factor (TF) was used in a placebo controlled pilot study of 20 patients
      with chronic fatigue syndrome (CFS). Efficacy of the treatment was evaluated by
      clinical monitoring and testing for antibodies to Epstein-Barr virus (EBV) and
      human herpes virus-6 (HHV-6). Of the 20 patients in the placebo-controlled trial,
      improvement was observed in 12 patients, generally within 3-6 weeks of beginning
      treatment. Herpes virus serology seldom correlated with clinical response. This
      study provided experience with oral TF, useful in designing a larger placebo
      controlled clinical trial.

PMID- 8993765
TI  - The influence of age on transfer factor treatment of cellular immunodeficiency,
      chronic fatigue syndrome and/or chronic viral infections.
AB  - A group of 222 patients suffering from cellular immunodeficiency (CID),
      frequently combined with chronic fatigue syndrome (CFS) and/or chronic viral
      infections by Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), were
      immunologically investigated and treated with transfer factor (TF). The age range
      was 17-77 years. In order to elucidate the influence of aging on the course of
      the disease and on treatment, 3 subgroups were formed: 17-43 years, 44-53 years,
      and 54-77 years. Six injections of Immodin (commercial preparation of TF by
      SEVAC, Prague) were given in the course of 8 weeks. When active viral infection
      was present, IgG injections and vitamins were added. Immunological investigation
      was performed before the start of therapy, and subsequently according to need,
      but not later than after 3 months. The percentages of failures to improve
      clinical status of patients were in the individual subgroups, respectively:
      10.6%, 11.5% and 28.9%. The influence of increasing age on the percentage of
      failures to normalize low numbers of T cells was very evident: 10.6%, 21.2% and
      59.6%. In individuals uneffected by therapy, persistent absolute lymphocyte
      numbers below 1,200 cells were found in 23.1%, 54.5% and 89.3% in the oldest
      group. Statistical analysis by Pearson's Chi-square test, and the test for linear
      trend proved that the differences among the individual age groups were
      significant. Neither sex, nor other factors seemed to influence the results. The
      results of this pilot study show that age substantially influences the failure
      rate of CID treatment using TF. In older people, it is easier to improve the
      clinical condition than CID: this may be related to the diminished number of
      lymphocytes, however, a placebo effect cannot be totally excluded.

PMID- 8993766
TI  - Transfer factor in chronic mucocutaneous candidiasis.
AB  - Fifteen patients suffering from chronic mucocutaneous candidiasis were treated
      with an in vitro produced TF specific for Candida albicans antigens and/or with
      TF extracted from pooled buffy coats of blood donors. CMI of the patients was
      assessed using the LMT and the LST in presence of candidine. The aim of the study
      was the clinical evaluation of TF treatment and the incidence of positive tests
      before, during, and after therapy. Immunological data were matched using the Chi
      square test. 87 LMT were performed for each antigen dose and at the dilution of
      1/50, 58.9% (33/56) tests were positive during non-treatment or non-specific TF
      treatment. On the contrary 83.9% (26/31) were positive during specific TF
      treatment (P < 0.05). In the LST, a significant decrease of thymidine uptake in
      the control cultures in presence of autologous or AB serum was observed when
      patients were matched according to non-treatment, and both non specific (P <
      0.05) and specific TF treatment (P < 0.01). Only during specific TF treatment was
      a significant increase of reactivity against the Candida antigen at the highest
      concentration noticed, when compared with the period of non specific treatment (P
      < 0.01). Clinical observations were encouraging: all but one patient experienced
      significant improvement during treatment with specific TF. These data confirm
      that orally administered specific TF, extracted from induced lymphoblastoid cell
      lines, increases the incidence of reactivity against Candida antigens in the LMT.
      LST reactivity appeared not significantly increased with respect to the periods
      of non treatment, but was significantly increased when it was compared to the non
      specific TF treatment periods. At the same time, a clinical improvement was
      noticed.

PMID- 8993767
TI  - Some properties and protective activity of specific DLE against Salmonella
      cholerae suis infection.
AB  - From a rabbit lymphoid tissue, twice immunized with a Salmonella ch. suis
      vaccine, was obtained a dialysable leucocyte extract (DLE) (m. w. 10,000Da;
      protein content 1.14 mg/ml; content of ribose 2.7 mg/ml; A260/A280 ratio 2.17 and
      pH 6.8). By gel filtration on Sephadex G-25, six peaks were obtained and activity
      was found in peak IV. The activity of the extract was determined by a dermo
      application test (DAT) on 10 cows. The protective effect was tested by a
      challenge with Salmonella ch. suis and Salmonella dublin pathogen strains on
      white mice intraperitoneally treated with DLE. The DAT proved to be positive in 8
      of the 10 cows. When applied on white mice, it induced a high specific protective
      effect against Salmonella ch. suis (70%), but not against Salmonella dublin
      infection.

PMID- 8993768
TI  - Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal
      carcinoma: a pilot study.
AB  - Overall survival of nasopharyngeal carcinoma (NPC) at UICC stage IV still remains
      unsatisfactory even with combination chemotherapy (CT) and radio-therapy (RT). In
      view of the association of reactivation of Epstein-Barr virus (EBV) with the
      development and recurrence of NPC, immunotherapy in the form of transfer factor
      (TF) with specific activity against EBV (TF-B1) was suggested as an adjuvant to a
      combination of CT and RT in order to improve survival. In the present study, 6
      UICC stage IV patients received TF-B1 and another 6 patients matched for disease
      stage were given TF prepared from peripheral blood leucocytes (TF-PBL). Results
      were compared with another 18 patients matched by age, sex, and stage of disease
      who received standard therapy without TF during the same period (C group). After
      a median follow up of 47.5 months, the survival for the TF-B1 group was found to
      be significantly better (P = < 0.05) than the PBL and C group. While the 8
      patients with distant metastasis (DM), not treated with TF-B1 (6 in the control
      and 2 in the PBL group), died due to progressive disease (average survival being
      14.3 months), both patients with DM in the TF-B1 group had complete remission:
      one died of tuberculosis after surviving for 3.5 years and another is still
      alive, disease free, after 4.2 years. Although the series involved a small number
      of cases, the apparent effect of adjuvant immunotherapy in the form of TF with
      anti-EBV activity is of considerable interest.

PMID- 8993769
TI  - Transfer factor as an adjuvant to non-small cell lung cancer (NSCLC) therapy.
AB  - The rationale for using transfer factor (TF) in lung cancer patients is that the
      possibility of improving their cell-mediated immunity to tumour associated
      antigens (TAA) may improve their survival. From Jan 1984 to Jan 1995, 99 non
      small cell lung cancer (NSCLC) resected patients were monthly treated with TF,
      extracted from the lymphocytes of blood bank donors. In the same period, 257
      NSCLC resected patients were considered as non-treated controls. The survival
      rates of the TF treated group appear significantly improved both for patients in
      stages 3a and 3b, and patients with histological subtype "large cell carcinoma"
      (P < 0.02). Survival of TF treated patients is also significantly higher (P <
      0.02) for patients with lymph node involvement (N2 disease). The results of this
      study suggest that the administration of TF to NSCLC resected patients may
      improve survival.

PMID- 8993770
TI  - A preliminary report on the use of transfer factor for treating stage D3 hormone
      unresponsive metastatic prostate cancer.
AB  - As conventional treatments are unsuccessful, the survival rate of stage D3
      prostate cancer patients is poor. Reports have suggested the existence of humoral
      and cell-mediated immunity (CMI) against prostate cancer tumour-associated
      antigens (TAA). These observations prompted us to treat stage D3 prostate cancer
      patients with an in vitro produced transfer factor (TF) able to transfer, in
      vitro and in vivo, CMI against bladder and prostate TAA. Fifty patients entered
      this study and received one intramuscular injection of 2-5 units of specific TF
      monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission was
      achieved in 2 patients, partial remission in 6, and no progression of metastatic
      disease in 14. The median survival was 126 weeks, higher than the survival rates
      reported in the literature for patients of the same stage.

PMID- 8993771
TI  - Use of transfer factor for the treatment of recurrent non-bacterial female
      cystitis (NBRC): a preliminary report.
AB  - Results of conventional treatment of female non-bacterial recurrent cystitis
      (NBRC) are discouraging. Most patients show an unexpected high incidence of
      vaginal candidiasis, while their cell mediated immunity to Herpes simplex viruses
      (HSV) and Candida antigens seems impaired, and it is known that the persistence
      of mucocutaneous chronic candidiasis is mainly due to a selective defect of CMI
      to Candida antigens. Twenty nine women suffering of NBRC, and in whom previous
      treatment with antibiotics and non-steroid anti-inflammatory drugs was
      unsuccessful, underwent oral transfer factor (TF) therapy. TF specific to Candida
      and/or to HSV was administered bi-weekly for the first 2 weeks, and then once a
      week for the following 6 months. No side effects were observed during treatment.
      The total observation period of our cohort was 24379 days with 353 episodes of
      cystitis recorded and a cumulative relapse index (RI) of 43. The observation
      period during and after treatment was 13920 days with 108 relapses and a
      cumulative RI of 23 (P < 0.0001). It, thus, seems that specific TF may be capable
      of controlling NBRC and alleviate the symptoms.

PMID- 8993772
TI  - An attempt to inhibit the course of amyotrophic lateral sclerosis (ALS) by
      suppressor factor.
AB  - Forty amyotrophic lateral sclerosis (ALS) patients were treated with suppressor
      factor. The therapy led to the normalization of the immunoregulatory index in
      approximately two thirds of the patients. The responder patients had a better
      clinical response, i.e. the degenerative process slowed down or it was even
      arrested. This favourable effect was accompanied with a significant increase in
      the patients' life span. When the therapy had no effect on the CD8 cells, it was
      discontinued. Stopping the therapy led to disease progression and death; thus, in
      some patients, therapy was carried out despite its failure to increase the CD8
      cell numbers. Substantial clinical improvement was noticed in these patients. The
      mean survival of patients with ALS was 2-3 years, whereas ALS patients treated
      with the suppressor factor survived on the average more than 5 years.

PMID- 8993773
TI  - Dialysable lymphocyte extract (DLyE) in infantile onset autism: a pilot study.
AB  - 40 infantile autistic patients were studied. They ranged from 6 years to 15 years
      of age at entry. 22 were cases of classical infantile autism; whereas 18 lacked
      one or more clinical defects associated with infantile autism ("pseudo-autism").
      Of the 22 with classic autism, 21 responded to transfer factor (TF) treatment by
      gaining at least 2 points in symptoms severity score average (SSSA); and 10
      became normal in that they were main-streamed in school and clinical
      characteristics were fully normalized. Of the 18 remaining, 4 responded to TF,
      some to other therapies. After cessation of TF therapy, 5 in the autistic group
      and 3 of the pseudo-autistic group regressed, but they did not drop as low as
      baseline levels.

PMID- 8993774
TI  - Dialyzable lymphoid extract (DLE) from mice resistant to STZ-induced
      diabetogenesis can interrupt the progress of diabetes in STZ-treated CD-1 mice.
AB  - DLE was prepared from the minority of euglycemic CD-1 mice, previously injected
      with STZ, and was administered to hyperglycemic CD-1 male mice 1, 2 and 3 weeks
      after completion of multidose STZ. Mice treated with DLE derived from 2 x 10(7)
      (IX) or 10(8) lymphocyte equivalents (lymph.equ) were significantly less
      hyperglycemic than the saline treated controls (P < 0.001). The effects of DLE
      remained evident for more than 10 weeks after the final DLE treatment. Mice
      treated with DLE prepared from diabetic mice (hg DLE) developed a somewhat more
      rapid onset of hyperglycemia than the STZ treated control animals, although this
      effect did not achieve statistical significance (P = 0.1). This DLE was absorbed
      on a rat insulinoma cell line (RIN), which contains interspecies cross-reacting
      islet antigens, and compared to the unabsorbed DLE. Mice treated with hg DLE
      preabsorbed on RIN cells, showed a slower onset of hyperglycemia. DLE prepared
      from euglycemia mice and the RIN-absorbed fraction were equally capable of
      preventing hyperglycemia (P < 0.05). In order to determine whether the DLE
      effects were genetically restricted, DLE was prepared from BALB/c mice, normally
      resistant to the diabetogenic effects of multidose STZ, both before and after STZ
      treatment. STZ primed CD-1 mice treated with 3 weekly doses of 2 x 10(7) lymph.
      equ. of untreated BALB/c derived DLE, STZ treated BALB/c derived DLE, and STZ
      treated CD-1 DLE were all less hyperglycemic than the control mice, who received
      saline (P < 0.001). However, mice treated with CD-1 DLE were less hyperglycemic
      than the mice given BALB/c derived DLE (P < 0.05). These effects were relatively
      long-lived. Mice that were given the > 3,500 Dalton fraction of CD-1 DLE were
      significantly less hyperglycemic than either the control mice or those treated
      with the < 3,500 Dalton fraction of CD-1 DLE (P < 0.05). Effects remained evident
      for more than 3 months after the last dose of DLE. Pancreatic tissue from the
      mice treated with the > 3,500 Dalton fraction of CD-1 derived DLE revealed
      slightly more islets of a slightly greater size with less surrounding
      inflammation than either control mice or mice treated with the < 3,500 Dalton
      fraction of DLE.

PMID- 8993775
TI  - Influence of a DLE-extracted lymphocytic suppressor factor on CsA-induced
      immunosuppression.
AB  - From dialyzable leucocyte extracts (DLE) we have purified a hydrophilic low-mol.
      wt. factor (about 1 kDa) which we have named lymphocytic suppressor factor (LSF)
      as it is able to suppress antigen- and mitogen-induced lymphocyte transformation
      and to prolong allograft survival in C57b/6N mice (H-2b) transplanted with fully
      mismatched skin from C3H/HeN mice (H-2k). At the molecular level LSF acts by
      inhibiting DNA replicational and transcriptional processes in activated
      lymphocytes, isolated rat hepatocyte nuclei, and cell-free systems. Amino acid
      analysis indicates that LSF is a peptide composed of Asp, Glu, Ser, Thr, Ala,
      Gly, Arg and probably Met, with the N-terminus blocked, possibly by pyroglutamic
      acid. When combined "in vitro" with cyclosporine A (CsA), LSF increased about 20
      times the potency of CsA in inducing suppression of mitogen-stimulated
      lymphocytes. In C57b/6N mice with skin graft from C3H/HeN mice and undergoing
      immunosuppression with CsA (50 mg/kg/day), the splenocyte LSF content increased
      about 5 times. However, LSF values returned to normal in mice recovering normal
      responsiveness due to progressive withdrawal of CsA. These data show that LSF has
      an important role in the development and maintenance of CsA-induced
      immunosuppression. We suggest that, by influencing DNA replicational and
      transcriptional processes of lymphocytes, LSF may play a role also in the onset
      and progression of AIDS induced by retroviruses.

PMID- 8993776
TI  - Dialysable leucocyte extract (DLE) reduces lipopolysaccharide-induced tumour
      necrosis factor secretion in human leucocytes.
AB  - Dialysable leucocyte extract (DLE), obtained from lysed leucocytes, provide
      clinical effectiveness in a broad spectrum of diseases. Tumour necrosis factor
      (TNF) is raised in AIDS patients leading to an increase in human immunodeficiency
      virus (HIV) replication in vitro [1,2], whereas progression to AIDS in
      asymptomatic HIV infected individuals is retarded under treatment with DLE. In
      the present study we tested the DLE effect in vitro on both TNF biological
      activity (cytotoxicity) in L929 cells and its induction by lipopolysaccharide
      (LPS) in human monocytes as well as in whole blood from healthy donors. When
      monocytic cells were simultaneously exposed to LPS and DLE during a period of 5
      1/2 hours, the induction of TNF was strongly diminished. The same inhibitory
      effect of DLE on TNF induction was observed when LPS was added to the culture
      medium prior to DLE. No significant effect of DLE on TNF-mediated cytotoxicity,
      even in the presence of the highest concentrations of DLE tested, was detected.
      DLE treatment of whole human blood regulates responses to LPS: simultaneous in
      vitro exposure to endotoxin provokes a remarkable decrease (4- and 1.6-fold) of
      TNF release. In pre-incubation experiments, TNF production was largely reduced or
      completed abrogated. These results could, in part, explain the in vivo observed
      effect, when under treatment with this extract, the progression to AIDS of HIV
      infected individuals was retarded. The results suggest that "natural' substances
      like DLE may be important immunomodulators in inflammatory diseases.

PMID- 8993777
TI  - The effect of DLE fractions on GM-progenitors of haematopoietic stem cells in
      vitro.
AB  - Dialysable leucocyte extract (DLE) prepared from buffy coats of human blood,
      potentiates the effect of Colony-stimulating factor (CSF) on the growth of
      granulocyte-macrophage colony forming cell (GM-CFC) colonies in vitro. This
      relative increase of the number of colonies is apparent when diluted CSF (present
      in lung conditioning medium) as a control, and DLE, in a wide range of
      concentrations are added to the culture of mouse bone marrow cells. Fractionation
      of DLE on Amicon membranes revealed that the activity resides in molecules of 0-5
      kD. Molecules 5-10 kD have no potentiating effect. DLE and its fractions (0-5 kD,
      0-1 kD), except fractions 0-500 D and 5-10 kD, when added undiluted i.e. at the
      initial concentration, exerted a suppressive effect: colonies are not formed
      despite the presence of CSF. In a pilot experiment, it was shown that DLE is able
      to stimulate colony-forming activity of earlier progenitors of erythroid cells
      (BFUe), under the influence of erythropoietin.

PMID- 8993778
TI  - In vitro studies during long-term oral administration of specific transfer
      factor.
AB  - 153 patients suffering from recurrent pathologies, i.e. viral infections
      (keratitis, keratouveitis, genital and labial herpes) uveitis, cystitis, and
      candidiasis were treated with in vitro produced transfer factor (TF) specific for
      HSV-1/2, CMV and Candida albicans. The cell-mediated immunity of seropositive
      patients to HSV-1/2 and/or CMV viruses was assessed using the leucocyte migration
      inhibition test (LMT) and lymphocyte stimulation test (LST) in presence of the
      corresponding antigens, and the frequency of positive tests before, during and
      after TF administration was studied. The data were stratified per type of test,
      antigen and the recipients' pathology, and statistically evaluated. For the LMT,
      a total of 960 tests were carried out for each antigen dilution, 3 different
      antigen dilutions were used per test. 240/960 tests (25.4%) were found positive
      during non-treatment or treatment with unspecific TF, whereas 147/346 tests
      (42.5%) were found positive when the antigen corresponding to the specificity of
      the TF administered to the patient was used (P < 0.001). When the data were
      stratified following pathology, a significant increased incidence of positive
      tests during specific treatment was also observed (0.0001 < P < 0.05). In the LST
      (1174 tests), a significant increase of thymidine uptake was observed in the
      absence of antigen (control cultures), during treatment with both specific and
      unspecific TF, but also in the presence of antigen and/or autologous serum during
      specific TF administration (P < 0.0001). TF administration also significantly
      increased the soluble HLA class I antigens level in 40 patients studied to this
      effect.

PMID- 8993779
TI  - An ethicist's commentary on the case of suspected poisoning.

PMID- 8993780
TI  - Newfoundland and Labrador veterinarians promote dog vaccinations.

PMID- 8993781
TI  - Losses over a 2-year period associated with fetal infection with the bovine viral
      diarrhea virus in a beef cow-calf herd in Saskatchewan.
AB  - In 1992, significant calf losses occurred between birth and weaning in a 650-cow
      Saskatchewan beef herd. These losses occurred subsequent to ill-thrift and
      disease, and every calf necropsied was found to be persistently infected with
      bovine viral diarrhea virus (BVDV). The objectives of this study were to describe
      the losses associated with fetal infection with BVDV in this herd and to
      determine why they occurred. For investigative purposes, blood samples were
      collected from the entire cow herd and the surviving calves at pregnancy testing
      in 1992, and tested by virus isolation for BVDV. Between 51 and 71 persistently
      infected calves were born in 1992. Bovine viral diarrhea virus was only isolated
      from calves. The only confirmed fetal infections with BVDV were recorded as the
      birth of persistently infected calves. However, abortions, reduced pregnancy
      rates, and delayed calvings were also recorded in the cow herd and may have been
      the result of fetal infections. The herd was monitored again in 1993. Fetal
      infections with BVDV were recorded as the birth of stunted, deformed, and
      persistently infected calves. The greatest losses due to fetal infection with
      BVDV in the 2 years of this study occurred in cows that were 3-years-old at
      calving (second calves). Bovine viral diarrhea virus appears to have remained
      endemic in this herd by transmission from persistently infected calves on young 3
      and 4-year-old cows to naive calved 2-year-old cows that were mingled with them
      annually for rebreeding. Significant numbers of the 2-year-old cows remained
      naive to BVDV, because they were segregated from persistently infected calves at
      weaning, preventing cross-infection with BVDV.

PMID- 8993782
TI  - Performance, survival, necropsy, and virological findings from calves
      persistently infected with the bovine viral diarrhea virus originating from a
      single Saskatchewan beef herd.
AB  - Fifty-one calves from 652 cows and heifers that calved on a Saskatchewan ranch in
      1992 were identified as persistently infected with bovine viral diarrhea virus
      (BVDV), based on virological and necropsy findings. Herd records suggested a
      further 20 calves that died between birth and weaning were probably also
      persistently infected. Subsequent to weaning, all surviving persistently infected
      calves were transferred to one pen in a 10,000 head commercial feedlot, to mimic
      normal management practice in western Canadian beef herds. On average, when
      compared with healthy, BVDV-negative herdmates, persistently infected calves were
      "poor doers" and had poor survivability, with only 4 persistently infected calves
      surviving to 1 year of age. There was no difference (P > 0.05) in survival
      between male and female persistently infected calves. The clinical, pathological,
      and virological findings from these persistently infected calves varied over
      time. The majority of persistently infected calves had gross pathological lesions
      at necropsy, consistent with mucosal disease. However, approximately 25% of the
      persistently infected calves had gross pneumonic lesions at necropsy, with no or
      only mild lesions of mucosal disease. A wide variety of other lesions were also
      noted in persistently infected calves at necropsy. Therefore, the possibility
      that BVDV-induced lesions can be misdiagnosed is very real. The results of this
      study indicate that persistent infection with BVDV should always be considered in
      calves with chronic ill thrift, chronic enteritis, or respiratory disease.

PMID- 8993783
TI  - Use of magnetic resonance imaging in the diagnosis of central vestibular disease.

PMID- 8993784
TI  - Cyclosporin treatment of perianal fistulas in dogs.
AB  - The purpose of this pilot study was to investigate the efficacy of cyclosporin in
      treating perianal fistulas (PAF) in dogs. Based on resolution of all fistulas in
      all dogs with remission times up to > 18 months, we conclude that cyclosporin
      therapy is the treatment of choice for PAF in dogs.

PMID- 8993785
TI  - Disseminated lymphangiosarcoma in a dog.
AB  - This case is unusual due to its extended clinical course. Clinical,
      histopathological, and immunohistochemical findings are presented.

PMID- 8993786
TI  - Systemic adverse reactions in young Simmental calves following administration of
      a combination vaccine.
AB  - Combination vaccines containing viral and bacterial antigens are commonly used in
      veterinary practice and have been associated with adverse reactions. A group of
      young Simmental calves developed fever and depression following administration of
      a mixed vaccine, and 1 died with pulmonary edema, suggesting that endotoxins or
      other bacterial components may interact synergistically with some adjuvants to
      cause an enhanced pathologic inflammatory response in some individuals.

PMID- 8993788
TI  - Tales from the other side: the virtues of opposite side radiography.

PMID- 8993787
TI  - Diagnostic ophthalmology.

PMID- 8993789
TI  - A prospective study of reproductive factors, oral contraceptive use, and risk of
      colorectal cancer.
AB  - To explore the roles of reproductive factors and oral contraceptive use in the
      etiology of colorectal cancer, we examined incident cases of colorectal cancer (n
      = 501) that occurred during 1,012,280 person-years of follow-up between 1980 and
      1992 in the Nurses' Health Study. The women completed mailed, self-administered
      questionnaires every 2 years to update information on the risk factors and major
      medical events. In multivariate analysis, the relative risk (RR) of colorectal
      cancer among women who experienced menarche at age 14 or older was 0.83 (95%
      confidence interval (CI) = 0.64-1.08) compared with women who had menarche at age
      13; women whose menarche occurred under age 12 were at higher risk (RR = 1.22;
      95% CI = 0.96-1.55, P for trend = 0.01). Compared with women whose first
      pregnancy was before age 24, the risk for colorectal cancer was significantly
      increased among women whose first pregnancy was at age 30 or older (RR = 1.57;
      95% CI = 1.15-2.14; P for trend = 0.02). No important associations were seen for
      parity or age at menopause. Women who used oral contraceptives for 96 months or
      longer had a 40% lower risk of developing colorectal cancer (RR = 0.60; 95% CI =
      0.40-0.89; P for trend = 0.02) compared with women who never used oral
      contraceptives. These prospective data suggest that a later age of menarche and
      use of oral contraceptives may reduce risk of colorectal cancer, whereas women
      with a later age at first pregnancy may have a higher risk.

PMID- 8993790
TI  - Coffee and tea and the risk of recurrent colorectal adenomas.
AB  - Consumption of coffee has been associated with a reduction in the risk of cancer
      of the colon, and (less consistently) drinking tea has been associated with a
      reduction in the risk of rectal cancer. The effect of these beverages on the risk
      of colorectal adenomas, however, has not been well investigated. We used data
      from an adenoma prevention trial to investigate these associations. Patients with
      at least one recent large bowel adenoma were followed with colonoscopy 1 and 4
      years after their qualifying examinations. Adenomas detected at the year 4
      colonoscopy were used as end points. A food frequency questionnaire was
      administered at study entry and study completion; average intake over the study
      period was used to estimate the exposures of interest. There was no apparent
      association between the intake of regular coffee, decaffeinated coffee, or tea
      and the risk of recurrent colorectal adenomas. The relative risks and 95%
      confidence intervals per cup daily were 0.96 (0.87-1.05) for regular coffee, 0.97
      (0.84-1.12) for decaffeinated coffee, and 1.02 (0.83-1.25) for tea. These
      negative findings were present both overall and for adenomas of the right and
      left large bowel.

PMID- 8993791
TI  - Hormone replacement treatment and breast cancer risk: an age-specific analysis.
AB  - The relationship between hormone replacement treatment (HRT) and breast cancer
      risk was considered in age-specific groups of women, combining data from two case
      control studies conducted between 1983 and 1994 in six Italian centers. Cases
      were comprised of 5984 women, below age 75 years, with histologically confirmed
      breast cancer, and controls were comprised of 5504 women admitted to the hospital
      for a wide spectrum of acute, nonneoplastic, nonhormone-related diseases. Ever
      use of HRT was reported by 6.1% of the cases and 5.5% of the controls,
      corresponding to a multivariate odds ratio (OR) of 1.2 [95% confidence interval
      (CI), 1.0-1.4]. A significant trend in risk with duration of use was observed.
      Separate analysis for women < 55, 55-64, and 65-74 years old at diagnosis showed
      that the excess risk of breast cancer associated with ever-use of HRT was not
      observed in the youngest age group (OR, 0.9) and increased with age at diagnosis
      to 1.2 (95% CI, 0.9-1.5) for women 55-64 years old and 1.6 (95% CI, 1.2-2.3) for
      those 65-74 years old at diagnosis. A significant trend in risk with duration was
      observed only in the oldest group (65-74 years old), with ORs of 1.6 (95% CI, 1.1
      2.3) and 2.2 (95% CI, 1.1-4.7), respectively, for < 60 and > or = 60 months of
      use. Thus, this study suggests that the relationship between HRT and breast
      cancer risk is influenced by age at diagnosis and that any risk-benefit
      assessment is particularly critical for women using HRT several years after
      menopause.

PMID- 8993792
TI  - Smoking and pancreatic cancer in men and women.
AB  - Most studies of smoking and pancreatic cancer have used male subjects or combined
      men and women together in statistical analyses. There is little information on
      the relative risk of smoking and pancreatic cancer in women. Because of the high
      case-fatality rate, many of these studies were also based on information gathered
      from proxy respondents, in which smoking habits may not be recalled with
      certainty. A hospital-based study of 484 male and female patients with pancreatic
      cancer and 954 control subjects was conducted based on direct interviews of
      incident cases. Compared to never smokers, the odds ratio (OR) for current
      cigarette smokers was 1.6 [95% confidence interval (CI), 1.1-2.4] for men and 2.3
      (95% CI, 1.4-3.5) for women. In women, but not in men, there was a trend in the
      ORs with years of daily cigarette consumption (P < 0.01). Filter cigarettes
      offered no protective advantage compared to nonfilter cigarettes. Among men, the
      OR was 2.1 (95% CI, 1.2-3.8) for pipe/ cigar smokers and 3.6 (95% CI, 1.0-12.8)
      for tobacco chewers. Tobacco smoke causes pancreatic cancer when inhaled into the
      lungs. Tobacco juice may also cause pancreatic cancer when ingested or absorbed
      through the oral cavity. These data suggest that smoking is a cause of pancreatic
      cancer in women and that the risks for female smokers are comparable to male
      smokers. Nevertheless, the causes of most pancreatic cancers are unknown.

PMID- 8993793
TI  - 5 alpha-reductase activity and prostate cancer: a case-control study using stored
      sera.
AB  - We report a nested case-control study of serum biomarkers of 5 alpha-reductase
      activity and the incidence of prostate cancer. From a cohort of more than 125,000
      members of the Kaiser Permanente Medical Care Program who underwent multiphasic
      health examinations during 1964-1971, we selected 106 incident prostate cancer
      cases. A control was pair matched to each case on age, date of serum sampling,
      and clinic location. Serum levels of total testosterone, free testosterone,
      androsterone glucuronide, and 5 alpha-androstane-3 alpha,17 beta androstanediol
      glucuronide (3 alpha-diol G) were measured on the stored samples and scored as
      quartiles. Potential confounders included alcohol, smoking, and body mass index.
      The adjusted odds ratios and 95% confidence intervals for a one quartile score
      increase were 1.00 (0.75-1.34) for total testosterone, 1.14 (0.86-1.50) for free
      testosterone, 1.13 (0.84-1.53) for androsterone glucuronide, and 1.16 (0.86-1.56)
      for 3 alpha-diol G. A limitation of this study is that there are two different 5
      alpha-reductase isoenzymes, only one of which is expressed in high levels within
      the prostate, yet both of which may affect serum biomarkers. Since the two
      isoenzymes are encoded on different chromosomes, variation in one would act as an
      independent source of measurement error in any analysis of serum biomarker
      effects of the other. Consequently, the odds ratios may be underestimated and the
      study, although negative, cannot exclude the previously hypothesized possibility
      that a positive relationship between intraprostatic 5 alpha-reductase activity
      and prostate cancer may exist. A clinical trial to test this hypothesis is under
      way.

PMID- 8993794
TI  - Risk of squamous cell carcinoma of the skin in relation to plasma selenium, alpha
      tocopherol, beta-carotene, and retinol: a nested case-control study.
AB  - We conducted a nested case-control study of squamous cell skin cancer (SCC) to
      determine whether risk was related to plasma concentrations of selenium, alpha
      tocopherol, beta-carotene, and retinol. We derived the study sample from
      participants in our Skin Cancer Prevention Study, all of whom had at least one
      basal cell or squamous cell skin cancer before study entry. Those who developed a
      new squamous cell skin cancer during the 3-5-year follow-up period were selected
      as cases (n = 132). Controls (n = 264) were chosen at random, with matching by
      age, sex, and study center, from among those who did not develop SCC but were
      being followed actively at the time the SCC case was diagnosed. Prediagnostic
      plasma samples were analyzed for alpha-tocopherol, beta-carotene, and retinol
      using high-performance liquid chromatography. Selenium determinations were made
      using instrumental neutron activation analysis. Odds ratios were computed using
      conditional logistic regression for matched samples. We found no consistent
      pattern of SCC risk associated with any of the nutrients examined. The odds
      ratios (95% confidence intervals) for the highest versus the lowest quartiles of
      beta-carotene, retinol, alpha-tocopherol, and selenium were 0.73 (0.38-1.41),
      1.43 (0.77-2.64), 0.89 (0.43-1.85), and 0.86 (0.47-1.58), respectively. Thus, our
      data add to the growing body of evidence that these nutrients, at the
      concentrations we evaluated, are not related strongly to SCC risk.

PMID- 8993796
TI  - Surrogate end-point biomarkers as measures of colon cancer risk and their use in
      cancer chemoprevention trials.
AB  - Surrogate end-point biomarkers (SEBs) have become widely used in short-term
      cancer chemoprevention trials in place of cancer end points. This paper discusses
      criteria relevant to the selection and validation of SEBs for colon cancer risk
      and the use of SEBs in colon cancer chemoprevention trials. As with a number of
      other cancers, colon carcinogenesis is the result of a multistep process in which
      an increasing number of alterations, including specific gene mutations, occur as
      cells progress from normal to precancerous states of increasing size and
      dysplasia to cancer and finally to metastatic disease. Ideally, a SEB would show
      differential expression between the various phases of colon carcinogenesis (i.e.,
      normal, premalignant, and malignant tissues) and be associated with risk of colon
      cancer. Some SEBs that do not meet these criteria may still be useful for
      demonstrating the effect of a particular agent. It is also necessary that a SEB
      be measured in tissues (or other sample material) accessible for multiple and
      sequential sampling and allow for development of appropriate quality control
      procedures. Some SEBs must have the potential for modulation by chemopreventive
      agents. Validation of SEBs for use in chemoprevention studies requires that a
      relationship between the marker and subsequent risk of cancer be established.
      Also, the assay reliability and accuracy for each SEB must be determined
      adequately in well-designed prospective studies.

PMID- 8993795
TI  - Micronuclei in exfoliated bladder cells among individuals chronically exposed to
      arsenic in drinking water.
AB  - Inorganic arsenic is an established cause of lung and skin cancer.
      Epidemiological evidence from Taiwan suggests that arsenic causes more fatal
      internal cancers, with the highest relative risks reported for bladder cancer. We
      conducted a cross-sectional biomarker study in a Chilean male population
      chronically exposed to high (70 subjects) and low (55 subjects) arsenic levels in
      their drinking water (average concentrations, 600 and 15 micrograms As/liter,
      respectively). A fluorescent version of the exfoliated bladder cell micronucleus
      (MN) assay was used employing fluorescence in situ hybridization with a
      centromeric probe to identify the presence (MN+) or absence (MN-) of whole
      chromosomes within micronuclei, thereby determining the mechanism of arsenic
      induced genotoxicity in vivo. We divided the study population into quintiles by
      urinary arsenic levels and found an exposure-dependent increase in micronucleated
      cell prevalence in quintiles 2-4 (urinary arsenic, 54-729 micrograms/liter). The
      largest increase appeared when quintile 4 was compared to quintile 1 [prevalence
      ratio, 3.0; 95% confidence interval (CI), 1.9-4.6]. The prevalence of MN+
      increased to 3.1-fold in quintile 4 (95% CI, 1.4-6.6), and the prevalence of MN
      increased to 7.5-fold in quintile 3 (95% CI, 2.8-20.3), suggesting that
      chromosome breakage was the major cause of MN formation. Prevalences of total MN,
      MN+, and MN- returned to baseline levels in quintile 5 (urinary arsenic, 729-1894
      micrograms/liter), perhaps due to cytostasis or cytotoxicity. These results add
      additional weight to the hypothesis that ingesting arsenic-contaminated water
      enhances bladder cancer risk and suggest that arsenic induces genetic damage to
      bladder cells at drinking water levels close to the current United States Maximum
      Contaminant Level of 50 micrograms/liter for arsenic.

PMID- 8993797
TI  - Multiple myeloma: clusters, clues, and dioxins.
AB  - Multiple myeloma (MM) is a B-cell neoplasm of unknown etiology. We searched for
      etiological clues by examining the literature on geographic clusters of MM. We
      searched the MEDLINE database from 1966 to 1996 for spatial occurrences of MM
      that were significantly greater than expected (spatial "clusters"). Eight
      clusters with verified diagnoses of MM were identified. All of the eight clusters
      occurred in locations that were proximate to a body of water. Six of these bodies
      of water are known to have been contaminated with dioxins. We hypothesize that
      the observed association between MM and proximity to bodies of water is caused by
      exposure to dioxins in individuals who consume local fish and seafood. This
      hypothesis is consistent with the significantly elevated risks for MM in groups
      with high consumption of dioxin-contaminated fish, e.g., Baltic Sea fishermen and
      Alaskan Indians, and among persons accidentally exposed to dioxins in Seveso,
      Italy. Dioxins are immunotoxic and inhibit the differentiation of B cells. Thus,
      dioxins are plausible myelomagens. A dioxin hypothesis could illuminate many
      epidemiological features of MM and may suggest new avenues for analytic research.

PMID- 8993798
TI  - Ki-ras mutation modifies the protective effect of dietary monounsaturated fat and
      calcium on sporadic colorectal cancer.
AB  - The geographic differences in the incidence of colorectal cancer have been mostly
      attributed to variations in diet. The diversity of the Mediterranean diet and the
      heterogeneity of acquired genetic alterations in colorectal cancer sets the stage
      for investigating the possible association between dietary factors and mutations
      in tumor genes known to play a role in the pathogenesis of these neoplasms. With
      this purpose, we have studied the Ki-ras gene in 108 colorectal cancers using
      archival tissue and epidemiological data from our previous case-control study.
      Mutations in exon 1 of the Ki-ras gene were detected by a PCR-single strand
      conformation polymorphism approach. A polychotomous logistic regression model was
      used to assess the significance of observed differences between wild-type and
      mutated tumors with respect to population controls in the different categories of
      nutrient consumption. Multivariate density models were used to adjust the
      correlation between nutrients and total energy. Our studies show that high
      consumption of monounsaturated fats, mostly derived from olive oil, is associated
      with a statistically significant decrease in the risk of cancer with wild-type Ki
      ras genotype but not of Ki-ras mutated cancers. Conversely, we find that high
      calcium intake is associated with a decreased risk of Ki-ras mutated tumors but
      not of wild-type tumors. Tumor genotyping can reveal epidemiological associations
      that are weak or unapparent when cases-control studies are not stratified by
      tumor genotype.

PMID- 8993799
TI  - Naturally occurring selenium compounds in cancer chemoprevention trials: a
      workshop summary.
AB  - Evidence from epidemiological studies and a human intervention trial indicates
      that selenium (Se) may have chemopreventive activity in humans. This report
      summarizes a workshop held by the National Cancer Institute to address the use of
      naturally occurring Se compounds in future cancer chemoprevention trials.
      Differences in the metabolism of inorganic and organic Se compounds can be seen
      both in the biochemical handling of these forms and in their kinetics in humans.
      Long-term supplementation could result in greater increases in muscle stores for
      organic rather than inorganic forms. Because of long half-lives, trials may have
      to be of long duration to assess efficacy and safety. The optimal size of dose
      for supplementation is controversial with respect to both efficacy and safety. In
      China, selenosis was observed in some individuals with a sustained intake of at
      least 750 micrograms/day but was not observed among others with intakes exceeding
      1 mg. These levels exceed the reference dose, a measure of the maximal safe
      intake, which is 350 micrograms/day. A large-scale Se human intervention trial in
      the United States suggests no harm due to long-term Se intake of more than 200
      micrograms/day. Se deficiency has been shown to have deleterious effects on the
      immune system, allowing, for example, a benign form of the Coxsackievirus to
      become virulent in mice. These recent results may provide an explanation of
      earlier findings showing a protective effect of elevated Se intakes against a
      mouse mammary tumor virus. Additional studies on the use of Se as a
      chemopreventive agent in man seem warranted.

PMID- 8993807
TI  - Analysis of reproducibility of reference lumen quantitation with intravascular
      ultrasound in stented coronary arteries.
AB  - Intravascular ultrasound is widely used to guide coronary stent implantation. The
      key quantitative criterion for successful implantation is the demonstration of
      adequate expansion of the stented lumen relative to that of the adjacent
      reference vessel segments. In this study we aimed to establish the
      reproducibility of intravascular ultrasound measurements of the reference
      segments in lesions undergoing coronary stenting. Measurements of the reference
      segment lumen dimensions warn made in a blinded fashion by two experienced
      observers, and reproducibility was assessed by calculating the mean difference
      and standard deviation of the paired measurements. The unselected intraobserver
      random variability of the mean reference lumen area measured 0.6 mm2. The
      interobserver random variability was 0.94 mm2. The intraobserver and
      interobserver variability of minimum lumen area within the stent was smaller,
      measuring 0.30 mm2 and 0.52 mm2, respectively. There was 91% intraobserver
      agreement, and 75% interobserver agreement, in identifying adequate stent
      expansion as defined by a stent-to-mean reference lumen area ratio of > 0.8. The
      potentially significant level of variability inherent in selecting and measuring
      the reference segments, and its impact on clinical decision-making, should be
      remembered when this method of assessing the acute quantitative outcome of stent
      implantation is applied.

PMID- 8993808
TI  - Lumenology: intracoronary ultrasound in search of tenths of millimeters.

PMID- 8993809
TI  - Pseudoaneurysm after cardiac catheterization: therapeutic interventions and their
      sequelae: experience in 86 patients.
AB  - After diagnostic cardiac catheterization in 8,715 patients, a pseudoaneurysm was
      diagnosed in 86 (1%) patients. Primary conservative management by repeated
      compression bandages (CB) or ultrasound guided compression (UGC) was attempted in
      all patients. Occlusion of the pseudoaneurysm was achieved significantly more
      often by UGC (41/47; 87%) than by CB (22/39; 56%; P = 0.016). Of 86 patients, 23
      (27%) required surgical treatment. Major clinical acute complications occurred
      after surgery in 8/23 cases (35%) versus 4/63 (6%; P = 0.0004) following
      successful CB or UGC. However, intention-to-treat analysis showed no difference
      in the rate of acute complications in the CB or UGC group (15.4% versus 12.8%, P
      = 0.7272), because of a trend towards a higher complication rate following
      secondary surgery in the UGC (4/6 = 66.7%), as compared to the CB group (4/17 =
      23.5%, P = 0.1589). During follow up, 22/64 (34%) patients reported persistent
      inguinal complaints, 9/15 (60%) after surgery and 13/49 (27%) after successful CB
      or UGC (P = 0.0169). However, according to the intention-to-treat analysis, there
      was no significant difference between the initial groups (CB: 26.1% versus UGC:
      39.0%, P = 0.2958). Despite a higher effectiveness of UGC to achieve occlusion of
      a pseudoaneurysm compared to CB (87% vs. 56%), UGC is not superior to CB because
      of a higher rate of acute complications as well as long-term complaints in those
      patients requiring secondary surgery in the UCG group as compared to the CB
      group.

PMID- 8993810
TI  - Ultrasound-guided compression repair and beyond.

PMID- 8993811
TI  - One balloon, one stent: an effective cost-containment strategy for elective stent
      deployment.
AB  - A cost-containment strategy to reduce stent procedure-related resources utilizing
      an integrated system comprised of a Stablizer guide wire, a Brite-Tip guiding
      catheter, and a single Titan balloon catheter for both lesion predilatation and
      poststent deployment was compared to a conventional strategy utilizing a
      nonintegrated guide wire, guiding catheter, and balloon components. Both groups
      were comparable with respect to demographics, number of lesions stented, and
      stents deployed per lesion. No differences in lesion length or pre- and poststent
      minimal luminal diameter were observed. Balloon use was significantly reduced
      using the integrated strategy when compared to the conventional strategy (1.3 +/-
      0.5 vs. 2.1 +/- 1.1; P < 0.01); overall nonstent-related resource utilization was
      significantly reduced ($747 +/- $401 vs. $1,093 +/- $467; P < 0.01). Procedural
      success rates were identical in both groups (100%), and no patient sustained
      subacute stent thrombosis or required target vessel revascularization at 1 mo
      follow-up. We conclude that the use of a single Titan balloon catheter as part of
      an integrated cost-containment strategy for both lesion predilatation and
      poststent deployment results in considerable cost savings while maintaining high
      procedural and clinical success rates.

PMID- 8993812
TI  - Guidelines for internal peer review in the cardiac catheterization laboratory.
      Laboratory Performance Standards Committee, Society for Cardiac Angiography and
      Interventions.
AB  - The Laboratory Performance Standards Committee of the Society for Cardiac
      Angiography and Interventions has proposed guidelines for establishing an
      internal peer review program in the cardiac catheterization laboratory. The first
      step is to establish a committee and a data base. This data base should include
      quality indicators that reflect: physician qualifications, outcomes of
      procedures, and processes of care. The outcomes must be risk-adjusted to account
      for the variable severity of illness. Data should be collected by catheterization
      laboratory personnel and entered into a laboratory-specific computerized data
      base. These data must be analyzed and organized into profiles that reflect the
      quality of care. Based on this information, the Committee would institute the
      following interventions to improve physician performance: education, clinical
      practice standardization, feedback and benchmarking, professional interaction,
      incentives, decision-support systems, and administrative interventions. The legal
      aspects of peer review are reviewed briefly.

PMID- 8993813
TI  - Intracoronary ultrasound before coronary interventions: a prospective comparison
      of two different catheters.
AB  - Intravascular ultrasound (IVUS) provides unique information about the coronary
      arterial wall that can be used to guide transcatheter therapy. In this
      prospective study, two different IVUS systems were compared with respect to
      feasibility of imaging before intervention and angiographic changes induced by
      the simple advancement of the catheter across the lesion. Eighty-five patients
      (mean age 59 +/- 10 yr, 11 female) were studied with IVUS before intervention. In
      34 patients, a 4.8 F (1.6-mm) IVUS catheter was used (Group I), whereas in the
      remaining 51 patients, a 3.5 F (1.2-mm) IVUS catheter was used (Group II).
      Quantitative angiography was performed before and after the IVUS study to
      determine potential changes in lumen diameter. Clinical and angiographic
      characteristics were similar in the two groups. A successful IVUS interrogation
      of the target lesion was obtained more frequently in Group II (45/51 (88%) vs.
      19/34 (56%) patients, P < 0.01). After the IVUS study, a change in minimal lumen
      diameter was seen in Group I (baseline 0.84 +/- 0.2 vs. final 1.17 +/- 0.2 mm, P
      < 0.001) and Group II patients (baseline 0.80 +/- 0.3 vs. final 1.03 +/- 0.4 mm,
      P < 0.01). In the 64 lesions successfully crossed, the absolute gain in lumen
      diameter was significantly higher in Group I (0.40 +/- 0.2 vs. 0.23 +/- 0.2 mm, P
      < 0.05). In addition, an inverse correlation was found between baseline minimal
      lumen diameter and the absolute lumen gain induced by the IVUS study in Group I
      (r = -0.47, P < 0.05) but not in Group II patients (r = -0.16, NS). Neither
      angiographic nor echogenic lesion characteristics were associated with the change
      in lumen diameter. When multivariate analysis was applied, catheter size was the
      only independent predictor of lumen gain induced by IVUS after adjustment. Thus,
      the advancement of IVUS catheters across severe coronary lesions induces
      significant angiographic changes consistent with plaque remodeling and a Dotter
      effect. The use of smaller catheters not only allows a higher number of lesions
      to be studied before intervention, but also lessens the mechanical disruption of
      the plaque, yielding a more accurate and veracious picture of baseline plaque
      characteristics.

PMID- 8993814
TI  - Intravascular ultrasound identification of stent entrapment in vivo with in vitro
      confirmation.
AB  - OBJECTIVES: One potential complication of stenting is "stent jail" due to
      placement of a stent across a side branch, which may impede additional
      interventions. Another form of stent entrapment may occur if the guidewire is
      accidentally withdrawn and then unknowingly passes through a stent loop during
      reentry with subsequent high pressure expansion. The purpose of this study was to
      evaluate this form of stent entrapment in vitro by intravascular ultrasound
      (IVUS). METHODS: A guidewire was passed through the end or middle diamonds of
      Palmaz-Schatz and Palmaz stents or the middle of Gianturco-Roubin stents. A 3.5
      mm balloon was inflated over the guidewire through the various side holes of the
      stents. RESULTS: IVUS images presented three distinct patterns depending on the
      type of stent and position of balloon entry: 1) external compression and loss of
      wall continuity in the Palmaz-Schatz and Palmaz stents, 2) displacement of the
      side diamond across the lumen, and 3) external compression of the Gianturco
      Roubin stent. The first and second patterns but not the third one were associated
      with impairment of lumen access. CONCLUSIONS: Based upon this in vitro
      verification, IVUS imaging can be used to identify the presence of stent
      entrapment in vivo.

PMID- 8993815
TI  - Vessel reconstruction in total coronary occlusions with a long subintimal wire
      pathway: use of multiple stents under guidance of intravascular ultrasound.
AB  - A frequent cause of failure of the recanalization of a total coronary occlusion
      is a subintimal pathway of the guide wire. Three cases of occluded right coronary
      arteries are presented in which a distal reentry into the true vessel lumen was
      achieved. Intravascular ultrasound was used to locate the exit and reentry of the
      guide wire, and to plan the position of multiple stents for the coverage of this
      subintimal pathway. In all cases antegrade flow to the distal coronary bed was
      restored.

PMID- 8993816
TI  - Use of intravascular ultrasound in evaluating repeated balloon rupture during
      coronary stenting.
AB  - Balloon rupture during coronary angioplasty is a well-recognized complication of
      PTCA. Coronary angiography commonly fails to elicit the cause of balloon
      perforation. We present a case with multiple balloon rupture during additional
      high-pressure inflations of a Palmaz-Schatz stent where intravascular ultrasound
      was useful in revealing a calcified lesion protruding through the struts of the
      stent.

PMID- 8993817
TI  - Emergency bypass surgery for failed coronary interventions.

PMID- 8993818
TI  - Validation of a new UNIX-based quantitative coronary angiographic system for the
      measurement of coronary artery lesions.
AB  - We describe a method of validation of computerized quantitative coronary
      arteriography and report the results of a new UNIX-based quantitative coronary
      arteriography software program developed for rapid on-line (digital) and off-line
      (digital or cinefilm) analysis. The UNIX operating system is widely available in
      computer systems using very fast processors and has excellent graphics
      capabilities. The system is potentially compatible with any cardiac digital x-ray
      system for on-line analysis and has been designed to incorporate an integrated
      database, have on-line and immediate recall capabilities, and provide digital
      access to all data. The accuracy (mean signed differences of the observed minus
      the true dimensions) and precision (pooled standard deviations of the
      measurements) of the program were determined x-ray vessel phantoms. Intra- and
      interobserver variabilities were assessed from in vivo studies during routine
      clinical coronary arteriography. Precision from the x-ray phantom studies (6-In.
      field of view) for digital images was 0.066 mm and for digitized cine images was
      0.060 mm. Accuracy was 0.076 mm (overestimation) for digital images compared to
      0.008 mm for digitized cine images. Diagnostic coronary catheters were also used
      for calibration; accuracy.varied according to size of catheter and whether or not
      they were filled with iodinated contrast. Intra- and interobserver variabilities
      were excellent and indicated that coronary lesion measurements were relatively
      user-independent. Thus, this easy to use and very fast UNIX based program appears
      to be robust with optimal accuracy and precision for clinical and research
      applications.

PMID- 8993820
TI  - Coronary bypass on a catheter: sweeping the thrombus and friable material under a
      vein.

PMID- 8993819
TI  - Percutaneous revascularization of an extensively diseased saphenous vein bypass
      graft with a saphenous vein-covered Palmaz stent.
AB  - A 68-year-old man developed unstable angina 12 years following coronary artery
      bypass surgery. Angiography revealed an extensive area of severe stenosis and
      diminished distal flow in a right coronary artery vein bypass graft. Given the
      high distal embolism rate associated with conventional catheter-based treatment
      of old degenerated vein grafts, the diseased area was "relined" with a composite
      autologous saphenous vein-covered stent. The procedure was performed using
      modifications of standard PTCA methods and resulted in a widely patent, smooth
      lumen. This initial case demonstrates that a degenerated saphenous vein graft can
      be successfully revascularized with an autologous saphenous vein-covered stent in
      an attempt to minimize the potential complications of standard catheter-based
      revascularization methods.

PMID- 8993821
TI  - New sheath for vascular access and subcutaneous drug administration: multicenter
      clinical trial for pain prevention after cardiac catheterization.
AB  - A new vascular sheath design (anesthesia infusion sleeve, or AIS) was developed
      to enable administration of local anesthetics or other medications into the
      subcutaneous tissue around an arterial or venous insertion site without any
      additional needle sticks or manipulation. Design, animal testing, and an initial
      small single-site clinical study have previously been published. The current
      study was multicenter and randomized 80 patients to use of a standard sheath for
      vascular access or the AIS. Pain associated with sheath placement, postprocedure
      pain, and pain associated with sheath removal before and during manual
      compression was recorded. Baseline pain was identical in both the standard and
      AIS groups. Pain during infiltration and with initial femoral artery compression
      was significantly lower in the AIS group. A quality of life questionnaire
      indicated that the AIS sheath was associated with less discomfort and was
      preferred over a standard sheath in patients who had had a previous procedure
      performed. The AIS represents a simple addition to standard sheath design,
      offering superior pain control during removal compared to the standard technique,
      without the need for systemic analgesics or additional needle punctures.

PMID- 8993822
TI  - The interventional vascular access sheath--the legacy of Donald T. Desilets, M.D.
      (1935-1996)

PMID- 8993823
TI  - Coronary vein flow velocity changes during transluminal balloon angioplasty: a
      study using the Doppler guide wire.
AB  - The coronary flow velocity changes in the great cardiac and middle cardiac veins,
      induced by intracoronary administration of nitroglycerine, adenosine, and during
      percutaneous transluminal coronary angioplasty, were evaluated in 12 patients
      with significant coronary stenoses, using the Doppler wire (Flowire). Optimal
      spectral signals of the time-averaged peak flow velocity were obtained in 10
      patients. Nitroglycerine produced no significant flow velocity changes (P =
      0.13). Adenosine caused a significant augmentation of flow velocity compared to
      baseline (P = 0.003). During balloon inflation, venous flow velocity decreased (P
      = 0.007); however, the venous outflow did not cease. A pronounced venous
      hyperemic response, following balloon deflation, was also documented. The utility
      of continuous vein flow velocity monitoring with the Flowire, during high-risk
      and complicated coronary interventions remains to be elucidated.

PMID- 8993824
TI  - Coronary artery stenting postcardiac transplant: a report of two cases.
AB  - Coronary atherosclerosis remains a significant cause of morbidity and mortality
      following cardiac transplantation. Coronary artery bypass grafting, percutaneous
      transluminal coronary angioplasty, and directional coronary atherectomy have all
      been presented as attempted treatment options in this population with generally
      suboptimal results. Endovascular stenting is a new transcatheter treatment
      modality with unique potential advantages as compared to other transcatheter
      revascularization techniques. This report presents the use of endovascular
      stenting and 6-mo follow-up in two orthotopic cardiac transplant recipients with
      proximal stenotic posttransplant graft atherosclerosis.

PMID- 8993825
TI  - Percutaneous balloon pericardiotomy for the treatment of large, nonmalignant
      pericardial effusions in children: immediate and medium-term results.
AB  - To evaluate the safety and efficacy of pericardial window creation by
      percutaneous balloon dilation in children with recurrent, symptomatic,
      nonmalignant pericardial effusion, 6 boys and 4 girls, age 5-12 yr, underwent the
      procedure using the subxiphoid approach. The procedure was successful in 9
      patients. There was one case with rupture of the balloon and entrapment of its
      distal part within the pericardium. During follow-up (mean 14.6 mo) there was
      reaccumulation of fluid only in the patient in whom rupture of the balloon had
      occurred. No other complications were noted. Thus, percutaneous balloon
      pericardiotomy appears to be a safe and effective technique for the creation of a
      pericardial window in children with nonmalignant pericardial effusions, and may
      be used as an alternative to surgical window creation.

PMID- 8993826
TI  - Pulse-spray thrombolysis in acutely obstructed coronary artery in critical
      situations.
AB  - Pulse-spray thrombolysis (PST) was performed to treat large coronary thrombus in
      3 patients in critical situations. The originally developed pump system and a
      custom infusion catheter (SciMed/Boston Scientific, Maple Grove, MN) were used in
      combination. Case 1, a 48-yr-old male with extensive anterior myocardial
      infarction, failed to be recanalized by systemic thrombolysis. He underwent
      emergent coronary angiography, which revealed proximal occlusion of a large left
      anterior descending artery (LAD). TIMI 3 flow was achieved after 20 min with
      200,000 units of urokinese by PST, followed by balloon angioplasty. In case 2, a
      57-yr-old male, subacute stent thrombosis occurred 4 days after two and a half
      Palmatz-Schatz stents were implanted in mid-LAD. TIMI 3 flow was recovered at 20
      min with 240,000 units of urokinese and an additional 72,000 units of rt-PA,
      followed by redilatation with a quarter-size larger balloon than that used in
      stent deployment. In case 3, a 70-yr-old male, during ultrasound study for
      unstable angina, a massive thrombotic complication occurred which occluded the
      left main trunk. PST was immediately performed under cardiac resuscitation, and
      the patient recovered from shock after 15 min. TIMI 3 flow was restored after 25
      min. Two Palmatz-Schatz stents were implanted after thrombus completely
      disappeared. There were no complications, including distal embolization, intimal
      dissection, or bleeding. There was also no recurrence of the ischemic event. PST
      may be considered a potential treatment modality for coronary artery disease
      where large thrombus plays a major role.

PMID- 8993827
TI  - New concept in coronary angioplasty: dilatation with a helical balloon that
      allows simultaneous autoperfusion.
AB  - These preclinical studies investigate a new concept in coronary angioplasty and
      balloon catheter technology (the P100 catheter). The study sought to evaluate the
      morphology of experimental coronary arterial plaques dilated with the P100 in
      comparison to standard balloons, to determine the in vitro flow rates occurring
      during the inflation of the P100 in comparison to available perfusion catheters,
      and to assess the in vivo coronary flow velocity and the presence of ischemia
      during prolonged inflations with the P100. The development of myocardial ischemia
      is a major limitation of standard balloon angioplasty. To limit ischemia,
      autoperfusion catheters have been developed, in which blood flows through the
      balloon in the central catheter shaft. However, as the flow lumen profile is
      reduced to enhance the performance of these devices, so is the accompanying flow.
      An angioplasty catheter was designed to evaluate the feasibility of continuous
      autoperfusion around the dilatation balloon. The balloon surface was engineered
      to develop a helical trough for blood flow to occur during inflation. Arterial
      plaque morphology following angioplasty with the P100 (n = 8) and with standard
      balloons (n = 8) was evaluated in a swine model. In vitro flow rates during
      inflation of the P100 and available perfusion catheters were determined using 33%
      glycerol solution. In vivo coronary flow velocity was determined with a Doppler
      tipped wire during 60-min continuous inflations with the P100, and 15-sec
      inflations with a standard balloon in 12 vessel segments in 7 dogs; using 3.0-3.5
      mm-diameter balloons. All lesions were successfully dilated (< 50% luminal
      diameter stenosis) with the P100 and standard balloons. There were no morphologic
      differences in plaques dilated with P100 compared to standard balloons. In vitro
      flow rates with conventional 3.0-mm balloon perfusion catheters ranged from 27.1
      +/- 2.1 ml/min (RX Flowtrack) to 38.7 +/- 0.9 ml/min (Stack Perfusion), P < .05.
      Flow with the P100 ranged from 54.8 +/- 4.3 ml/min (2.5-mm balloon) to 103.2 +/-
      4.5 ml/min (3.5-mm balloon), P < .05. Distal average peak coronary flow velocity
      during prolonged P100 inflations varied from 69 +/- 7% of baseline at 5 min to 83
      +/- 8% of baseline at 40 min, with an upward trend in velocity the longer the
      balloon was inflated. Hemodynamics remained stable. Experimental plaques are
      successfully dilated with a helical balloon by a mechanism that appears similar
      to the dilatation mechanism of standard balloons. These preclinical studies show
      that angioplasty and autoperfusion can be accomplished by a balloon that does not
      have complete surface area contact with the vessel wall. A gap created by the
      helix can thus provide a conduit for blood flow. Clinical studies will determine
      whether this innovation, which alters the tubular geometry of current angioplasty
      balloons, will provide autoperfusion and equivalent dilatation effects in human.

PMID- 8993828
TI  - Occipital infarction following coronary angiography.

PMID- 8993829
TI  - Receptor tyrosine kinase signaling in vascular development.

PMID- 8993830
TI  - Ras(leu61) blocks differentiation of transformable 3T3 L1 and C3H10T1/2-derived
      preadipocytes in a dose- and time-dependent manner.
AB  - To investigate the functional relationship between the transforming ability of
      Ras and its role as an integral component of the differentiation-promoting
      insulin signaling pathway, we introduced a leu61-activated ras gene into the Ras
      transformable 3T3 L1 (ATCC CCL92.1) and a number of C3H10T1/2-derived
      preadipocytic cell lines. The results demonstrate a quantitative reciprocal
      regulation of differentiation and several transformation-associated properties in
      response to graded levels of ras gene expression, with the loss of
      differentiative capacity, morphological transformation, stimulation of
      proliferation, and anchorage-independent growth requiring increasing levels of
      Ras(leu61) protein. Furthermore, using novel, tightly regulatable 3T3 L1
      transfectants, we demonstrated that Ras(leu61) effectiveness in blocking
      adipocytic differentiation is strictly dependent on the timing of its expression
      relative to cell growth arrest, with ras(leu61) expression being ineffective at
      inhibiting differentiation or inducing morphological transformation once the
      differentiative process has commenced. Moreover, rasleu61 induction failed to
      substitute for or enhance the c-Ras-dependent differentiative insulin signal,
      even under conditions in which it did not induce transformation. Therefore,
      although necessary for insulin signal transduction, the Ras signal alone is not
      sufficient to induce adipocytic differentiation in this system. Consistent with
      its established role as a downstream effector of Ras, v-Raf expression mirrored
      the Rasleu61 effects on adipocytic differentiation and transformation.

PMID- 8993832
TI  - Constitutive expression of full-length c-Myb transforms avian cells
      characteristic of both the monocytic and granulocytic lineages.
AB  - Both viral Myb (v-Myb) and cellular Myb (c-Myb) are nuclear sequence-specific DNA
      binding proteins that can function as transcriptional activators. v-Myb, encoded
      by avian myeloblastosis virus, induces acute monoblastic leukemia in chickens and
      transforms avian myelomonocytic cells in culture. The normal c-Myb protein is
      essential for hematopoietic development. Previous reports suggested that
      truncation of c-Myb is required for oncogenic transformation of avian
      myelomonocytic cells in culture. In this study, we demonstrate that constitutive
      expression of full-length c-Myb can transform avian myelomonocytic cells isolated
      from embryonic yolk sacs by using a strategy to enhance the efficiency of
      infection and/or expression of c-myb-containing viruses. c-Myb-transformed
      myelomonocytic cells display a different phenotype than cells transformed by v
      MybAMV or other Myb mutants. c-Myb-transformed yolk sac cells are heterogeneous
      populations with characteristics of both the macrophage and granulocyte lineages.
      Our results demonstrate that constitutive expression of full-length c-Myb is
      sufficient to activate its oncogenic potential, but that the target cells for c
      Myb are relatively rare and presumably quite immature.

PMID- 8993831
TI  - Absence of MEF2 binding to the A/T-rich element in the muscle creatine kinase
      (MCK) enhancer correlates with lack of early expression of the MCK gene in
      embryonic mammalian muscle.
AB  - During skeletal muscle development, different types of muscle fibers are
      generated, which express different combinations of muscle-specific gene products.
      For example, the muscle creatine kinase gene (MCK) is highly expressed in fetal
      but not embryonic myotubes. We performed transient transfections of CAT reporter
      constructs, driven by the MCK promoter with variable lengths of 5'-flanking
      sequence, into primary cultures of embryonic and fetal muscle cells. Reporter
      activity was observed in fetal but not embryonic muscle cells. We assayed the
      ability of nuclear extracts prepared from embryonic and fetal muscle and C2C12
      myotubes to bind specific regulatory elements in the MCK enhancer. The profile of
      DNA/protein complexes resulting from electrophoretic mobility shift assays was
      qualitatively the same with all extracts used when the oligonucleotide probes
      represented the MCK-E-box, MHox site, CArG-box, and AP2 site. In contrast, no
      binding activity to the MEF2 site was observed with embryonic nuclear extract.
      Interestingly, MEF2 mRNAs and proteins were detected in both fetal and embryonic
      muscle, with the exception of the MEF2D1b isoform, which is restricted to fetal
      muscle. Furthermore, we found that protein phosphatase inhibitors included in the
      preparation of embryonic nuclear extracts or added to the medium of transfected
      embryonic myotubes can restore MEF2 DNA binding activity, as well as reporter
      activity driven by the MCK promoter and partial transcriptional activation of the
      endogenous MCK gene. We propose that phosphorylation of MEF2 regulates its
      activity and represents an important aspect of the mechanism controlling stage
      specific transcription during skeletal myogenesis.

PMID- 8993833
TI  - Growth inhibitory effect of interferon-beta is associated with the induction of
      cyclin-dependent kinase inhibitor p27Kip1 in a human gastric carcinoma cell line.
AB  - The effect of IFN-beta on cell growth and the mechanism of growth modulation was
      examined in human gastric carcinoma cell lines. IFN-beta inhibited the cell
      growth of TMK-1 cells, whereas it did not affect the growth of the other three
      cell lines (MKN-7, -28, and -45). The number of apoptotic cells in IFN-beta
      treated TMK-1 cells was 2-fold the number of those in control TMK-1 cells,
      whereas the induction of apoptosis was not observed in IFN-beta-treated MKN-28
      cells. IFN-beta enhanced the expression of cyclin-dependent kinase inhibitor
      p27Kip1 at mRNA and protein levels. The increased p27Kip1 bound preferentially to
      CDK6. The phosphorylation level of retinoblastoma protein in TMK-1 cells was
      reduced by IFN-beta treatment. IFN-beta did not affect the expression of cell
      cycle regulators in MKN-28 cells. These results suggest that the induction of
      p27Kip1 by IFN-beta might confer inhibition of cell growth, leading to subsequent
      apoptosis in TMK-1 cells.

PMID- 8993834
TI  - A decrease in the intracellular guanosine 5'-triphosphate concentration is
      necessary for granulocytic differentiation of HL-60 cells, but growth cessation
      and differentiation are not associated with a change in the activation state of
      Ras, the transforming principle of HL-60 cells.
AB  - We found that when human promyelocytic leukemic cells (HL-60 cells) were induced
      to differentiate along the granulocytic lineage by two diverse mechanisms
      (starvation for an essential amino acid or treatment with DMSO), there was a
      marked decrease in the intracellular guanosine 5'-triphosphate (GTP)
      concentration with no change in the guanosine 5'-diphosphate (GDP) concentration.
      Differentiation was prevented by guanine or guanosine in a dose-dependent manner.
      We showed that: (a) guanine had to be converted to a nucleotide because it did
      not prevent differentiation of hypoxanthine-guanine phosphoribosyltransferase
      deficient HL-60 cells; (b) the effect of guanine correlated with a return of the
      cytosolic GTP:GDP ratio to normal; and (c) other purine bases were not effective.
      We hypothesized that the decreased GTP:GDP ratio in differentiating HL-60 cells
      might decrease the relative amount of GTP bound to Ras, a key regulatory GTP
      binding protein important to cell growth and differentiation. Consistent with
      data showing that HL-60 cells harbor an activating N-Ras mutation, we found that
      the percentage of Ras molecules in the GTP-bound state was high in proliferating
      HL-60 cells (27 +/- 3%) compared with other cultured mammalian cells (< 1%);
      however, we found no change in the activation state of Ras when cells ceased to
      proliferate and differentiated in response to DMSO, amino acid deprivation, or
      inhibitors of guanylate synthesis. We conclude that: (a) a decrease in the
      intracellular GTP concentration is necessary for HL-60 cells to undergo
      granulocytic differentiation; and (b) although a high degree of Ras activation
      contributes to the malignant phenotype of the cell, there is no change in the
      activation state of Ras during granulocytic differentiation.

PMID- 8993835
TI  - Transforming growth factor beta induces anchorage-independent growth of NRK
      fibroblasts via a connective tissue growth factor-dependent signaling pathway.
AB  - Connective tissue growth factor (CTGF) is a M(r)38,000 cysteine-rich peptide, the
      synthesis and secretion of which are selectively induced by transforming growth
      factor beta (TGF-beta). The relationship of CTGF to TGF-beta action on
      fibroblastic cells is not well understood. TGF-beta has the unique ability to
      stimulate the growth of normal fibroblasts in soft agar, a property of
      transformed cells. We have investigated whether CTGF can substitute for TGF-beta
      or whether CTGF action is essential for TGF-beta to stimulate anchorage
      independent growth (AIG) of NRK fibroblasts. Our studies demonstrate that CTGF
      cannot induce AIG of NRK fibroblasts. However, CTGF synthesis and action are
      essential for the TGF-beta-induced AIG of NRK fibroblasts. Anti-CTGF antibodies
      specifically block TGF-beta-induced AIG but have no effect on platelet-derived
      growth factor or epidermal growth factor-induced growth in monolayer cultures and
      do not cross-react with platelet-derived growth factor or TGF-beta. Clones of NRK
      fibroblasts that express an antisense CTGF gene (NRK-ASCTGF), which blocks the
      expression of the endogenous CTGF gene, do not respond to TGF-beta in the AIG
      assay. The growth and morphology of the cells (NRK-ASCTGF) in monolayer culture
      are unaltered from the parent NRK cell line. The addition of recombinant CTGF to
      the NRK-ASCTGF clones in the presence of TGF-beta restores the AIG response of
      the cells. These studies demonstrate that the TGF-beta stimulation of NRK
      fibroblast AIG is dependent on events induced via the synergistic action of CTGF
      dependent and CTGF-independent signaling pathways.

PMID- 8993836
TI  - Hepatocyte nuclear factor-3 alpha promoter regulation involves recognition by
      cell-specific factors, thyroid transcription factor-1, and autoactivation.
AB  - The hepatocyte nuclear factor-3 alpha (HNF-3 alpha) and -3 beta proteins share
      homology in the winged helix/fork head DNA binding domain and regulate cell
      specific transcription in hepatocytes and respiratory epithelium. In this study,
      we used transfection assays to demonstrate that the -520 nucleotides upstream of
      the rat HNF-3 alpha gene were sufficient for cell-specific expression. We
      identified binding sites for a liver and kidney-enriched nuclear factor and a
      kidney-enriched protein that recognizes two distinct promoter elements. We showed
      that the rat HNF-3 alpha promoter binds the HNF-3 protein isoforms, which may
      serve an auto- and/or cross-regulatory role. Furthermore, we showed that
      cotransfection of the thyroid transcription factor-1 expression vector enhanced
      HNF-3 alpha promoter activity. We discuss these results with respect to the
      transcriptional induction of the HNF-3 alpha gene in respiratory epithelium
      during embryogenesis. Because the HNF-3 alpha promoter region bound nuclear
      factors in kidney extracts, we used in situ hybridization to demonstrate that it
      was expressed in the urothelium of the renal pelvis in adult and embryonic
      kidney. We also report on a novel expression pattern of HNF-3 alpha in the
      epithelium of the urinary bladder, penile urethra, and the prostate gland, and
      show that its expression in the intestinal epithelium increases from the proximal
      duodenum to distal ileum. We also demonstrate that HNF-3 alpha is abundantly
      expressed in the colonic epithelium. Furthermore, we use the HNF-3 DNA binding
      consensus sequence to identify putative target genes in the renal pelvis and gut
      epithelium.

PMID- 8993837
TI  - Role of alpha 5 beta 1 integrin in determining malignant properties of colon
      carcinoma cells.
AB  - We characterized the expression of alpha 5 beta 1 integrin in two distinct
      phenotypes of colon carcinoma cell lines. Highly invasive colon cell lines
      (designated Group I cell lines) expressed higher levels of integrin alpha 5 beta
      1 mRNA and protein than did poorly invasive colon cell lines (designated Group
      III cell lines). The relatively high expression of integrin alpha 5 beta 1 in
      Group I cell lines resulted in strong enhancement of cell adhesion to fibronectin
      (FN) tissue culture plates, whereas Group III cell lines showed little or no
      enhancement of cell adhesion by coating. There was no significant difference
      between Group I and Group III cell lines with respect to cell adhesion to laminin
      and collagen IV. Cell adhesion to FN in Group I cells was mainly mediated by
      integrin alpha 5 beta 1 because a monoclonal anti-alpha 5 subunit antibody could
      block cell adhesion to FN, whereas anti-alpha 2 and anti-alpha 3 antibodies had
      no effect on cell adhesion to FN. The divergence of alpha 5 beta 1 expression in
      these two distinct colon carcinoma phenotypes suggested that high expression of
      alpha 5 beta 1 might contribute to malignant progression in this model system. To
      test this hypothesis, GEO cells, a Group III cell line that did not express alpha
      5 integrin, were transfected with the alpha 5 subunit. Stable transfection of
      alpha 5 sense cDNA into a typical GEO-limiting dilution clone led to the
      expression of alpha 5 subunit mRNA and cell surface alpha 5 beta 1 protein. The
      alpha 5 sense transfectants showed enhanced attachment to FN-coated plates and
      were more tumorigenic when the cells were injected into athymic nude mice. These
      results indicate that inappropriately high alpha 5 beta 1 integrin expression
      contributes to malignant progression in colon carcinoma.

PMID- 8993838
TI  - Retinoic acid and IFN inhibition of cell proliferation is associated with
      apoptosis in squamous carcinoma cell lines: role of IRF-1 and TGase II-dependent
      pathways.
AB  - Both retinoids and IFNs are known to inhibit proliferation of many normal and
      transformed cells and to have an in vivo antitumor effect against a variety of
      cancers, including squamous cell carcinoma. Because the combination of IFNs and
      all-trans retinoic acid (RA) could improve their antitumor effectiveness
      (depending on the histological origin and state of differentiation of the cells),
      we compared the activity of RA and/or IFN-alpha 2b with regard to the mechanism
      of growth inhibition of ME180 and SiHa cell lines, derived from squamous cervix
      carcinoma at different stages of differentiation. We reported previously that, in
      the ME180 cell line, the combined treatment significantly increased the growth
      inhibitory effect of the single agents. Here, we show that the SiHa cell line
      appears more sensitive to IFN-alpha 2b than the ME180 cell line, and resistant to
      RA, which does not significantly inhibit SiHa cell growth. Induction of apoptotic
      cell death clearly occurs and correlates with the inhibition of cell
      proliferation in both cell lines. It is interesting that the induction of the
      transcription factor IFN regulatory factor 1 correlates with the subsequent
      induction of apoptosis, whereas TGase I and II expression does not. In
      particular, TGase I and II appear differentially expressed in the ME180 and SiHa
      cell lines; i.e., TGase I is expressed in ME180 and specifically inhibited by RA,
      whereas TGase II is expressed in SiHa. It is interesting that both IFN-alpha and
      RA are able to increase TGase II expression and activity in this cell line.

PMID- 8993839
TI  - Fenretinide: induction of apoptosis and endogenous transforming growth factor
      beta in PC-3 prostate cancer cells.
AB  - N-(4-Hydroxyphenyl)retinamide (4-HPR, Fenretinide) is a retinoid derivative with
      antineoplastic activity in various tumor types including prostate carcinoma. The
      mechanism of action of 4-HPR toxicity is unknown. 4-HPR induces apoptosis in
      leukemia- and lymphoma-derived cells, neuroblastoma, and small cell lung cancers.
      The present study was designed to investigate: (a) the mechanism of 4-HPR
      cytotoxicity in prostate cancer cells; and (b) correlate increased expression of
      transforming growth factor beta 1 (TGF beta 1) with induction of apoptosis. 4-HPR
      exposure to PC-3 cells in vitro was associated with apoptosis as evidenced by
      increased incidence of hypodiploid nuclei in propidium iodide fluorescence
      histograms and DNA fragmentation. An increase in the percentage of nuclei in the
      G1 phase of the cell cycle preceded induction of apoptosis. TGF beta 1-increased
      expression was noted in mRNA levels and in secretion of active TGF beta 1 into
      culture media. TGF beta 1 and TGF-beta receptor type II detected
      immunohistochemically were increased in 4-HPR-treated PC-3 cells. Furthermore, 4
      HPR-induced cytotoxicity in PC-3 cells was abrogated by the addition of anti-TGF
      beta 1 antibody. In BT-20 cells, a 4-HPR-resistant breast carcinoma cell line,
      apoptosis was not observed after exposure to 4-HPR nor was TGF beta 1 expression
      enhanced in stained cells or in conditioned media. It is concluded that 4-HPR
      induces the expression of TGF beta 1 in association with the induction of
      apoptosis.

PMID- 8993840
TI  - Activation of extracellular signal-regulated kinase (ERK) by mitogenic stimuli is
      repressed in v-Src-transformed cells.
AB  - Stimulation of mitogenic signaling pathways results in transient activation of
      the extracellular signal-regulated kinase (ERK) subfamily of mitogen-activated
      protein kinases (MAPK) in normal cells. We demonstrate here that activation of
      ERKs in response to serum or phorbol ester stimulation was markedly repressed in
      three different rodent fibroblast cell lines stably transformed by v-Src.
      Activation of the MAPK/ERK kinase (MEK) was also repressed in v-Src-transformed
      cells, indicating that the repression occurs upstream of ERK. Consistent with
      repression occurring predominantly at the level of MEK, the phosphatase inhibitor
      orthovanadate could restore ERK activation to a limited extent in some but not
      all v-Src-transformed cell lines. A similar repression of ERK activation was
      observed in v-Ras- and v-Raf-transformed cells. In addition, ERK activity was not
      constitutively elevated in exponentially growing cells transformed by v-Src, v
      Ras, or v-Raf as compared with normal cells. These results establish that the ERK
      activation pathway is repressed in rodent fibroblasts stably transformed by viral
      oncoproteins that chronically stimulate receptor tyrosine kinase signaling
      pathways. Furthermore, our findings suggest that elevated ERK activity above
      basal levels is not required for maintaining cell transformation by these
      oncoproteins. Taken together, these results indicate that ERK signaling pathways
      are subject to negative feedback regulation upstream of ERK as a consequence of
      oncogenic transformation.

PMID- 8993841
TI  - Molecular determinants of peptide and non-peptide binding to the AT1 receptor.
AB  - 1. Several residues critically involved in AT1 receptor ligand-binding and
      activation have now been identified based on mutational and biochemical studies.
      2. Asp281 and Lys199 of the rat AT1 receptor ion-pair with Arg2 and the Phe3
      alpha-COOH of angiotensin II (AngII), respectively, and the Asp281/Arg2
      interaction is critical for full agonist activity. 3. Agonist activity of AngII
      also requires an interaction of the Phe8 side chain with His256, which is
      achieved by docking of the alpha-COOH with Lys199. Non-peptide agonists interact
      with Lys199 and His256 in a similar fashion. 4. The crucial acid pharmacophores
      of AngII and the non-peptide antagonist, losartan, appear to occupy the same
      space within the receptor pocket. Binding of the tetrazole anion moiety of
      losartan involves multiple contacts, such as Lys199 and His256. However, this
      interaction does not involve a conventional salt bridge, but rather an unusual
      lysine-aromatic interaction. 5. Asp1 of AngII forms an ion-pair with His183,
      which stabilizes the receptor-bound conformation of AngII but is not critical for
      receptor activation. 6. These interactions and the involvement of other residues
      in stabilizing the wild-type receptor conformation or in receptor/G-protein
      coupling are considered here. 7. Despite these insights, considerable effort is
      still needed to elucidate how ligand binding induces receptor activation, what
      determines the specificity of AT1 receptor coupling to multiple G-proteins and
      the in vivo role of receptor down-regulation.

PMID- 8993842
TI  - Human type-1 angiotensin II (AT1) receptor gene structure and function.
AB  - 1. The type-1 angiotensin II (AngII) receptors, designated AT1, mediate most of
      the biological actions of the peptide hormone AngII. They are the most recent
      drug target for the treatment of hypertension and cardiac failure and basic
      research is now focusing on the mechanisms that regulate their expression. 2. In
      humans there is a single AT1 gene. It encodes a 47 kb pre-mRNA containing five
      exons, with the previously described AT1 open reading frame (ORF) on exon 5.
      Alternative splicing results in the production of mature mRNA that are translated
      at different efficiencies and encode two receptor isoforms. The inclusion of exon
      2 markedly inhibits translation of the down-stream ORF, both in vitro and in
      vivo. Nonetheless, this exon is present in up to one-half of AT1 mRNA in all
      tissues studied. 3. Transcripts containing exon 3 spliced to exon 5 encode a
      receptor with an amino-terminal extension of 32 amino acids and represent up to
      one-third of total AT1 mRNA in each tissue examined. In vitro, these latter
      transcripts are translated to produce a longer receptor and, in transfected
      cells, they encode a functional AT1 receptor with ligand-binding and signalling
      properties similar to those of the short isoform. 4. Exon 4 is of minor
      significance as it is rarely spliced into AT1 mRNA. 5. These data indicate that,
      in addition to characterizing factors that modulate AT1 promoter activity and RNA
      stability, it is important to analyse the splicing patterns of this gene when
      studying the regulation of its expression.

PMID- 8993843
TI  - Molecular mechanisms of angiotensin II (AT1A) receptor endocytosis.
AB  - 1. Angiotensin II (AngII) initiates a variety of cellular responses through
      activation of type 1 (AT1; with subtypes AT1A and AT1B) and type 2 (AT2) cell
      surface angiotensin receptors. Both AT1 and AT2 receptors couple to
      heterotrimeric guanyl nucleotide binding proteins (G-proteins) and generate
      intracellular signals following recognition of extracellular AngII, but only AT1
      is targeted for the rapid ligand-stimulated endocytosis (internalization) typical
      of many plasma membrane receptors. 2. AT1 endocytosis proceeds through clathrin
      coated pits and is independent of G-protein coupling which predicts that the
      AngII-AT1 receptor complex attains a conformation necessary for interaction with
      the endocytotic machinery, but separate from receptor signalling activation. 3.
      The function of AT1 endocytosis and the reason for the disparity between AT1 and
      AT2 endocytosis is not fully appreciated, but the latter probably reflects
      differences in the primary amino acid sequence of these two receptor types. 4.
      For many receptors that undergo internalization, it has been established that
      internalization motifs (2-6 amino acids, often incorporating crucial tyrosine and
      hydrophobic amino acids) within the cytoplasmic regions of the receptor mediate
      the selective recruitment of activated receptors into clathrin-coated pits and
      vesicles. 5. Mutagenesis studies on the AT1A receptor, aimed at identifying such
      motifs, reveal that sites within the third cytoplasmic loop and the cytoplasmic
      carboxyl terminal region are important for AngII-stimulated AT1A receptor
      endocytosis.

PMID- 8993844
TI  - Transgenic rats: tools to study the function of the renin-angiotensin system.
AB  - 1. The development of the transgenic technology for the rat allowed the
      evaluation of gene functions in the cardiovascular system in vivo. New insights
      have been gained particularly in the functions of the renin-angiotensin system
      (RAS), as most transgenic rat models established so far carry genes of this
      system. 2. TGR(mREN2)27 is a rat harbouring the mouse Ren-2 gene and exhibiting
      fulminant hypertension. The plasma RAS in this animal is down-regulated; however,
      the tissue-specific production of angiotensin II is activated (e.g. in the
      adrenal gland, the brain and the vessel wall). The physiological consequences of
      this activation, which finally leads to hypertension, can be studied in
      TGR(mREN2)27, rendering it a valuable tool in the functional analysis of tissue
      RAS. 3. TGR(hREN) and TGR(hAOGEN) carry the human genes for renin and
      angiotensinogen, respectively. In these animals the species-specific interaction
      of the two proteins and the expression pattern of the genes can be studied.
      Furthermore, these animals can be used to test renin-inhibitory drugs for use in
      antihypertensive therapy. 4. Further refinement of transgenic methodology (e.g.
      by the development of gene targeting in rats), should enhance our understanding
      of the functions of the RAS in cardiovascular regulation.

PMID- 8993845
TI  - Angiotensin receptors and development: the kidney.
AB  - 1. This brief review examines the evidence that angiotensin II (AngII) is
      essential for kidney development. 2. Several components of the renin-angiotensin
      system (RAS) are detected in the foetal kidney early in development. 3.
      Angiotensin II is essential for normal foetal and neonatal renal function. 4.
      Angiotensin II receptors transduce important signals leading to growth and
      development. 5. Angiotensin receptor subtypes show spatial and temporal
      specificity of localization throughout renal development. 6. Angiotensin
      converting enzyme (ACE) inhibition or AngII receptor blockade (specifically AT1
      subtype blockade) results in functional and structural abnormalities of the
      developing kidney in both experimental and clinical situations. 7. While chronic
      postnatal RAS blockade in rats is associated with structural damage to tubules
      and blood vessels of the kidney, reports differ on whether treatment also affects
      glomerular induction and growth. 8. In metanephric organ culture, glomerular
      induction proceeds despite AngII receptor blockade. 9. In summary, the evidence
      suggests that AngII is not essential for nephron induction and glomerular
      development in the rat kidney. However, AngII is essential for normal growth and
      development of renal tubules and vasculature.

PMID- 8993846
TI  - Role of AT1 receptors in the central control of sympathetic vasomotor function.
AB  - 1. In a number of species, high concentrations of angiotensin II (AngII)
      receptors have been found in the rostral ventrolateral medulla (RVLM) in the
      hindbrain, which is an important region involved in the modulation of sympathetic
      vasomotor tone. The present review describes studies in which the contribution of
      angiotensin receptors in the brainstem to cardiovascular regulation, in
      particular sympathetic vasomotor reflexes, has been examined in conscious and
      anaesthetized rabbits. 2. In conscious rabbits, fourth ventricular infusions of
      AngII produced dose-dependent pressor responses as does 400 times less than
      equipressor intravenous doses. Chronic baroreceptor denervation increased the
      sensitivity to AngII by 1000-fold. Administration of prazosin i.v. blocked the
      pressor response, suggesting that the mechanism involved sympathetic
      vasoconstriction. 3. The pattern of haemodynamic changes in response to AngII
      injected into the fourth ventricle (4V) involved decreased total peripheral
      conductance and mesenteric conductance, but a rise in hindlimb conductance.
      Sinoaortic denervation changed the hindlimb fall in conductance to an increase,
      suggesting that muscle vasomotor pathways were particularly inhibited by
      baroreceptor feedback mechanisms. 4. In anaesthetized rabbits, infusion of AngII
      into the RVLM increased blood pressure and transiently increased resting renal
      sympathetic nerve activity. The renal sympathetic baroreflex curves were shifted
      to the right and the upper plateau of the sympathetic reflex increase was
      markedly increased. 5. The pressor actions of 4V AngII were blocked by
      administration of a peptide antagonist injected into the RVLM or by the
      angiotensin AT1 antagonist losartan injected into the 4V. These results suggest
      that mainly AT1 receptors are involved and that the RVLM is a likely candidate
      site for the modulation of the renal sympathetic baroreflex. 6. Losartan
      administration into the 4V in conscious rabbits increased resting renal
      sympathetic tone and enhanced renal sympathetic baroreflex and chemoreflexes. 7.
      Our studies suggest that there are sympathoexcitatory AT1 receptors in the RVLM
      accessible to AngII from the cerebrospinal fluid. In addition, an AT1 receptor
      pathway normally inhibits the sympathoexcitation produced by baroreceptor
      unloading or chemoreceptor activation. The effect of losartan suggests that there
      is greater tonic activity within the sympathoinhibitory pathways. These two
      actions suggest that angiotensin receptors in the brainstem modulate sympathetic
      responses to specific afferent inputs, thus forming part of a potentially
      important mechanism for the integration of characteristic autonomic response
      patterns.

PMID- 8993847
TI  - Physiological actions of angiotensin II mediated by AT1 and AT2 receptors in the
      brain.
AB  - 1. Autoradiographic binding studies have shown that the AT1 receptor is the
      predominant angiotensin II (AngII) receptor subtype in the central nervous system
      (CNS). Major sites of AT1 receptors are the lamina terminalis, hypothalamic
      paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal
      ventrolateral medulla, nucleus of the solitary tract and the intermediolateral
      cell column of the thoraco-lumbar spinal cord. 2. While there are differences
      between species, AT2 receptors are found mainly in the cerebellum, inferior olive
      and locus coeruleus of the rat. 3. Circulating AngII acts on AT1 receptors in the
      subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to
      stimulate neurons that may have a role in initiating water drinking. 4. Centrally
      administered AngII may act on AT1 receptors in the median preoptic nucleus and
      elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor
      response and vasopressin secretion. 5. Recent evidence shows that centrally
      administered AT1 antagonists inhibit dipsogenic, natriuretic, pressor and
      vasopressin secretory responses to intracerebroventricular infusion of hypertonic
      saline. This suggests that n angiotensinergic neural pathway has a role in
      osmoregulatory responses. 6. Central angiotensinergic pathways which include
      neural inputs to the rostral ventrolateral medulla may use AT1 receptors and play
      a role in the function of sympathetic pathways maintaining arterial pressure.

PMID- 8993848
TI  - Functions of angiotensin peptides in the rostral ventrolateral medulla.
AB  - 1. It was first shown several years ago that the rostral part of the
      ventrolateral medulla (VLM) contains a high density of receptor binding sites for
      angiotensin II (AngII). In the present paper we briefly review recent studies
      aimed at determining the actions of both exogenous and endogenous angiotensin
      peptides in the rostral VLM, as well as their specific sites of action. 2. The
      results of these studies have shown that angiotensin peptides can excite pressor
      and sympathoexcitatory neurons in the rostral VLM, but do not appear to affect
      non-cardiovascular neurons in this region. 3. It is known that pressor neurons in
      the rostral VLM include both catecholamine and non-catecholamine neurons. There
      is evidence that, at least in conscious rabbits, both of these types of neurons
      are activated by AngII. The specific endogenous angiotensin peptide or peptides
      that affect pressor neurons in the rostral VLM have not yet been definitively
      identified. 4. It is also possible that different angiotensin peptides may have
      different effects on pressor neurons in the rostral VLM, mediated by different
      receptors. Further studies will be needed to define these different functions as
      well as the specific receptors and cellular mechanisms that subserve them.

PMID- 8993849
TI  - Regulation of renal tubular sodium transport by angiotensin II and atrial
      natriuretic factor.
AB  - 1. The effects of angiotensin II (AngII) on water and electrolyte transport are
      biphasic and dose-dependent, such that low concentrations (10(-12) to 10(-9)
      mol/L) stimulate reabsorption and high concentrations (10(-7) to 10(-6) mol/L)
      inhibit reabsorption. Similar dose-response relationships have been obtained for
      luminal and peritubular addition of AngII. 2. The cellular responses to AngII are
      mediated via AT1 receptors coupled via G-regulatory proteins to several possible
      signal transduction pathways. These include the inhibition of adenylyl cyclase,
      activation of phospholipases A2, C or D and Ca2+ release in response to inositol
      1,4,5,-triphosphate or following Ca2+ channel opening induced by the arachidonic
      acid metabolite 5,6,-epoxy-eicosatrienoic acid. In the brush border membrane,
      transduction of the AngII signal involves phospholipase A2, but does not require
      second messengers. 3. Angiotensin II affects transepithelial sodium transport by
      modulation of Na+/H+ exchange at the luminal membrane and Na+/HCO3 cotransport,
      Na+/K(+)-ATPase activity and K+ conductance at the basolateral membrane. 4.
      Atrial natriuretic factor (ANF) does not appear to affect proximal tubular sodium
      transport directly, but acts via specific receptors on the basolateral and brush
      border membranes to raise intracellular cGMP levels and inhibit AngII-stimulated
      transport. 5. It is concluded that there is a receptor-mediated action of ANF on
      proximal tubule reabsorption acting via elevation of cGMP to inhibit AngII
      stimulated sodium transport. This effect is exerted by peptides delivered at both
      luminal and peritubular sides of the epithelium and provides a basis for the
      modulation by ANF of proximal glomerulotubular balance. The evidence reviewed
      supports the concept that in the proximal tubule, AngII and ANF act
      antagonistically in their roles as regulators of extracellular fluid volume.

PMID- 8993850
TI  - Angiotensin II and the adrenal.
AB  - 1. Angiotensin II (AngII) evokes a variety of physiological responses in the
      adrenal gland. It is the major regulator of aldosterone secretion, in the medulla
      it enhances catecholamine release and it exerts trophic effects in the adrenal
      and stimulates growth factor secretion. 2. Angiotensin II acts via binding to
      specific receptors, located on the plasma membrane. Two pharmacologically
      distinct AngII receptor subtypes, type 1 (AT1) and type 2 (AT2) receptors, have
      been identified using the non-peptide antagonists Dup753 and PD 123177,
      respectively, and cDNA encoding each type have been identified. 3. In the
      adrenal, the AT1 receptor modulates all the known biological effects of AngII.
      The expression of the AT1 receptor is modulated at the mRNA and protein levels by
      many factors: conditions that increase levels of AngII (low sodium diet,
      renovascular hypertension, AngII infusion) up-regulate AT1 receptor mRNA levels
      and binding and increase aldosterone secretion. 4. A tissue renin-angiotensin
      system has been found in the adrenal, suggesting an important paracrine role for
      AngII in aldosterone regulation. 5. The possible involvement of AT1 receptors in
      human disease has been investigated by examining the role of AngII receptors in
      adrenal tumours. Binding and gene expression studies have shown that AngII
      receptors are abundantly expressed in aldosterone-producing adenoma (APA). 6.
      Densitometric analysis of AT1 expression in APA showed no significant differences
      compared with normal and non-tumorous adrenal. In addition, no mutations in the
      coding sequence of the AT1 receptor have been found to date in adrenal tumours.

PMID- 8993851
TI  - Endogenous angiotensin II levels and the mechanism of action of angiotensin
      converting enzyme inhibitors and angiotensin receptor type 1 antagonists.
AB  - 1. Modification of endogenous angiotensin II (AngII)-mediated processes by
      inhibitors of the angiotensin-converting enzyme (ACE) and antagonists of the
      angiotensin type 1 (AT1) receptor is dependent upon both the levels of each agent
      in the plasma and tissues and on the concomitant changes in plasma and tissue
      AngII levels. 2. Both ACE inhibitors and AT1 receptor antagonists increase renin
      secretion and angiotensin peptide formation in plasma and extrarenal tissues.
      Clinical doses of ACE inhibitors produce incomplete inhibition of ACE and the
      increased AngI levels act to restore AngII towards basal levels. Clinical doses
      of AT1 receptor antagonists produce incomplete blockade of AT1 receptors and the
      increased AngII levels in plasma and extrarenal tissues counteract (to an unknown
      degree) the effects of the antagonist. 3. The effects of ACE inhibitors and AT1
      receptor antagonists on AngII levels show tissue specificity. Angiotensin II
      mediated processes in the kidney are most sensitive to inhibition by these
      agents. ACE inhibitors reduce renal AngII levels at doses much less than those
      required to reduce AngII levels in plasma and other tissues. Moreover, in
      contrast to increased AngII levels in plasma and extrarenal tissues, renal AngII
      levels do not increase in response to AT1 receptor antagonists. The inhibition of
      AngII-mediated processes in the kidney may, therefore, play a primary role in
      mediating the effects of ACE inhibitors and AT1 receptor antagonists on blood
      pressure and other aspects of cardiovascular function and structure. 4.
      Combination of an ACE inhibitor with an AT1 receptor antagonist prevents the rise
      in plasma AngII levels that occurs with AT1 receptor antagonism alone. This
      combination would, therefore, be predicted to produce more effective inhibition
      of endogenous AngII-mediated processes than either agent alone. We must await
      further studies to determine whether the combination of ACE inhibition and AT1
      receptor antagonism results in superior clinical outcomes.

PMID- 8993852
TI  - Structural changes in the renal vasculature in the spontaneously hypertensive
      rat: no effect of angiotensin II blockade.
AB  - 1. There is strong evidence for a renal basis to the development of hypertension
      in the spontaneously hypertensive rat (SHR). Alterations of the SHR renal
      vasculature, including the glomerulus, may be involved in the initiation and
      maintenance of hypertension in this animal model. 2. The arterial walls of pre
      glomerular vessels of the SHR are hypertrophied compared with WKY vessels. Unlike
      other vascular beds in the SHR, this hypertrophy is independent of angiotensin II
      (AngII). 3. Glomerular number and volume are similar between SHR and the
      normotensive Wistar-Kyoto (WKY) rats. These results provide no support for the
      theory that a reduced filtration surface area within the kidneys of the SHR
      contributes to the elevated blood pressure in these animals. 4. Intrarenal
      hypertrophy may have similar haemodynamic consequences to clipping of the main
      renal artery, as in Goldblatt hypertension. Further analysis of the role of pre
      glomerular arterial hypertrophy is warranted to determine its involvement in the
      initiation and maintenance of hypertension in the SHR.

PMID- 8993853
TI  - Cytokines and cardiac hypertrophy: roles of angiotensin II and basic fibroblast
      growth factor.
AB  - 1. While the haemodynamic influences that cause cardiac hypertrophy are well
      known, the cellular and molecular mechanisms by which a mechanical stimulus is
      translated into a growth response by cardiac muscle have remained uncertain. 2.
      Current evidence suggests that a number of trophic factors may be released by
      cellular constituents of the heart, acting in an autocrine or paracrine manner to
      influence the growth response and phenotype of neighbouring cells. 3. Angiotensin
      II, acting via the AT1 receptor subtype, and both basic fibroblast growth factor
      and heparin-binding epidermal growth factor have been shown to exert hypertrophic
      actions in vivo and in vitro. Studies also indicate that cardiac myocytes
      themselves are capable of releasing all of these cytokines in response to
      increased mechanical load.

PMID- 8993854
TI  - Experience with angiotensin II antagonists in hypertensive patients.
AB  - 1. The availability of orally active specific angiotensin receptor antagonists
      (AT1 antagonists) has opened new therapeutic choices and provided probes to test
      the specific role of the renin-angiotensin system in the pathogenesis of
      cardiovascular disease. 2. The data available so far suggest that the
      antihypertensive efficacy of angiotensin receptor antagonists is comparable to
      that of angiotensin-converting enzyme (ACE) inhibitors. This provides further
      evidence that this latter class of drugs exerts its effect mainly through
      blockade of the renin-angiotensin enzymatic cascade. As expected, the association
      of a diuretic exerts an equally strong additive effect to the antihypertensive
      efficacy of both classes of drugs. 3. The most common side effect of ACE
      inhibitors, dry cough, does not occur with AT1 antagonists, which confirms the
      long-held view that this untoward effect of the ACE inhibitors is due to renin
      angiotensin-independent mechanisms. 4. Long-term studies with morbidity/mortality
      outcome results are needed, before a definite position can be assigned to this
      newcomer in the orchestra of modern antihypertensive drugs. Notwithstanding, this
      new class of agents already represents an exciting new addition to our
      therapeutic armamentarium.

PMID- 8993855
TI  - Presence of angiotensin II AT2 receptor binding sites in the adventitia of human
      kidney vasculature.
AB  - 1. Angiotensin II (AngII) receptor subtypes in adult human kidney were
      pharmacologically characterized by in vitro autoradiography using the AngII
      receptor subtype-selective antagonists, losartan and PD 123319, and the
      sensitivity to the reducing agent, dithiothreitol. 2. High densities of AngII AT1
      receptor binding occur in the glomeruli and the inner stripe of the outer
      medulla, while a moderate AT1 receptor binding is localized in the proximal
      convoluted tubules. 3. AT2 receptor binding is observed predominantly in the
      intrarenal large blood vessels, including the arcuate, inter- and intra-lobular
      arteries, and in the renal capsule. 4. In the major renal artery, AT1 receptor
      binding is abundant in the media and adventitia, while AT2 receptor binding is
      observed mainly in the adventitia. 5. At the light microscopic level using
      emulsion autoradiography, AT1 receptors are localized in the glomeruli and
      juxtaglomerular apparatus, as expected. However, in larger renal blood vessels,
      including the arcuate arteries, inter- and intra-lobular arteries, intense AT2
      receptor labelling occurs primarily in the adventitia, while the endothelium and
      vascular smooth muscle layers contain only low levels of AngII receptor binding.
      6. These results indicate that the adult human kidney displays two
      pharmacologically distinct AngII receptor subtypes, with AT1 predominating in the
      glomeruli, juxtaglomerular apparatus, proximal tubules and the inner stripe of
      the outer medulla, while AT2 predominates in the adventitia of the arcuate and
      interlobular arteries and the renal capsule. The functional significance of AT2
      receptor binding sites in the adventitia of adult human kidney vessels remains to
      be elucidated.

PMID- 8993857
TI  - Biology of Isospora spp. from humans, nonhuman primates, and domestic animals.
AB  - Coccidial parasites of the genus Isospora cause intestinal disease in several
      mammalian host species. These protozoal parasites have asexual and sexual stages
      within intestinal cells of their hosts and produce an environmentally resistant
      cyst stage, the oocyst. Infections are acquired by the ingestion of infective
      (sporulated) oocysts in contaminated food or water. Some species of mammalian
      Isospora have evolved the ability to use paratenic (transport) hosts. In these
      cases, infections can be acquired by ingestion of an infected paratenic host.
      Human intestinal isosporiasis is caused by Isospora belli. Symptoms of I. belli
      infection in immunocompetent patients include diarrhea, steatorrhea, headache,
      fever, malaise, abdominal pain, vomiting, dehydration, and weight loss, blood is
      not usually present in the feces. The disease is often chronic, with parasites
      present in the feces or biopsy specimens for several months to years. Recurrences
      are common, Symptoms are more severe in AIDS patients, with the diarrhea being
      more watery. Extraintestinal stages of I. belli have been observed in AIDS
      patients but not immunocompetent patients. Treatment of I. belli infection with
      trimethoprim-sulfamethoxazole usually results in a rapid clinical response.
      Maintenance treatment with trimethoprim-sulfamethoxazole is needed because
      relapses often occur once treatment is stopped.

PMID- 8993856
TI  - Role of oxidants in microbial pathophysiology.
AB  - Reactive oxidant species (superoxide, hydrogen peroxide, hydroxyl radical,
      hypohalous acid, and nitric oxide) are involved in many of the complex
      interactions between the invading microorganism and its host. Regardless of the
      source of these compounds or whether they are produced under normal conditions or
      those of oxidative stress, these oxidants exhibit a broad range of toxic effects
      to biomolecules that are essential for cell survival. Production of these
      oxidants by microorganisms enables them to have a survival advantage in their
      environment. Host oxidant production, especially by phagocytes, is a
      counteractive mechanism aimed at microbial killing. However, this mechanism may
      be contribute to a deleterious consequence of oxidant exposure, i.e.,
      inflammatory tissue injury. Both the host and the microorganism have evolved
      complex adaptive mechanisms to deflect oxidant-mediated damage, including
      enzymatic and nonenzymatic oxidant-scavenging systems. This review discusses the
      formation of reactive oxidant species in vivo and how they mediate many of the
      processes involved in the complex interplay between microbial invasion and host
      defense.

PMID- 8993858
TI  - Yersinia pestis--etiologic agent of plague.
AB  - Plague is a widespread zoonotic disease that is caused by Yersinia pestis and has
      had devastating effects on the human population throughout history. Disappearance
      of the disease is unlikely due to the wide range of mammalian hosts and their
      attendant fleas. The flea/rodent life cycle of Y. pestis, a gram-negative
      obligate pathogen, exposes it to very different environmental conditions and has
      resulted in some novel traits facilitating transmission and infection. Studies
      characterizing virulence determinants of Y. pestis have identified novel
      mechanisms for overcoming host defenses. Regulatory systems controlling the
      expression of some of these virulence factors have proven quite complex. These
      areas of research have provide new insights into the host-parasite relationship.
      This review will update our present understanding of the history, etiology,
      epidemiology, clinical aspects, and public health issues of plague.

PMID- 8993859
TI  - Waterborne protozoan pathogens.
AB  - Protozoan parasites were the most frequently identified etiologic agents in
      waterborne disease outbreak from 1991 to 1994. The waterborne parasites Giardia
      lamblia, Naegleria fowleri, Acanthamoeba spp., Entamoeba histolytica,
      Cryptosporidium parvum, Cyclospora cayetanesis, Isospora belli, and the
      microsporidia are reviewed. For each parasite, the review includes history, life
      cycle, incidence, symptoms, and therapy. Clinical detection methods are compared,
      and emerging technologies are discussed. Information on the association of these
      parasites with waterborne outbreaks is reviewed. Current information on protozoan
      parasites identified as etiological agents in waterborne outbreaks is discussed.
      Water industry issues related to recent disease outbreaks are examined in the
      context of water quality testing regulations for G. lamblia and those proposed
      for C. parvum. The review identifies the limitations of the American Society of
      Testing and Materials water-testing method for these parasites. An overview of
      federal regulations affecting the water industry and laboratories that test for
      water quality is also provided. The article highlights the importance of the
      clinical laboratory as a frontline defense for the detection of infectious
      organisms. The review points to the need for clinical laboratories, physicians,
      and public health personnel to cooperatively plan and assess the challenge of
      meeting this potential public health threat.

PMID- 8993864
TI  - Functional bone imaging in the detection of ischemic osteopathies.
AB  - The efficiency and accuracy of a functional imaging technique in the detection of
      ischemic osteopathy is reviewed over a 10-year period. The study includes 161
      patients who had trauma, 101 patients who had suspected Perthes disease, 43
      patients who had dysbarism, and 22 patients who had renal transplants on steroid
      immunosuppressive therapy. After intravenous injection of 7.7 MBq kg-1 Tc-99m HDP
      data were collected on all patients during the first 20 minutes, accretion rate
      functional images were produced, and static bone scans performed after 3 hours.
      All patients were followed up until a definitive diagnosis (clinical and
      radiologic) of avascular necrosis or osteochondritis was confirmed or denied. Of
      the 327 patients studied, 114 had positive accretion rate images and 213 negative
      accretion rate images. There were 8 false-positive scan results and 2 false
      negative scan results. The overall predictive accuracy was 97% (disease
      prevalence 33%) with a sensitivity rate of 98% and a specificity rate of 96%. The
      authors conclude that the technique is a valuable predictive diagnostic indicator
      for ischemic osteopathies.

PMID- 8993865
TI  - Sequential Tc-99m MDP bone scans after cementless total hip arthroplasty in
      asymptomatic patients.
AB  - PURPOSE: To evaluate the distribution and degree of radioactivity on sequential
      Tc-99m methylene diphosphonate (Tc-99m MDP) scans in the diagnosis of
      postoperative loosening in asymptomatic patients who underwent cementless total
      hip replacement. MATERIAL AND METHODS: Tc-99m MDP scans were obtained every three
      months where possible, for one year in those patients who underwent total hip
      replacement using a Harris Galante cementless prosthesis. Eighty-three scans from
      45 patients were obtained. Uptake was assessed within the five periprosthetic
      zones (zone 1: greater trochanter; 2: lateral stem of the prosthesis; 3: tip of
      the prosthesis; 4: medial stem of the prosthesis; and 5: lesser trochanter) using
      an arbitrary 5-point grading system. Grade 1 indicated normal uptake and Grade 5
      indicated highest uptake. The grade of uptake within each zone was then analyzed
      against their postoperative ages. RESULTS: The radioactivity regressed to Grade 1
      or 2 from Grade 4 or 5 within 12 months after cementless total hip replacement in
      87.5% and 93.8% of patients in zones 2 and 4, respectively. Even though the
      radioactivity within zones 1, 3, and 5 tended to decrease, persistent elevation
      of activity (over grade 2) lasted up to 12 months after surgery in 31% or 37% of
      the patients. CONCLUSION: The radioactivity after cementless total hip
      replacement tended to regress in proportion to the postimplant age. The
      regression rate varied depending on the periprosthetic zones.

PMID- 8993866
TI  - Transient iodine organification defect in infants with ectopic thyroid glands.
AB  - BACKGROUND: Thyroid gland ectopy is the most common cause in infants with
      congenital hypothyroidism (CH). Its association with iodine organification
      defect, as suggested by positive perchlorate discharge test (PDT) has been
      reported. However, whether such an association represents a true or transient
      defect has not yet been determined. This finding has an important clinical,
      epidemiological, and genetic implications. OBJECTIVE: To determine the natural
      history of iodine organification defect in patients with CH caused by thyroid
      ectopy detected by neonatal screening. DESIGN: Prospective longitudinal study.
      SETTING: King Khalid University Hospital, Riyadh, Saudi Arabia. PATIENTS AND
      METHODS: PDT was performed, at the time of diagnosis and follow-up, in infants
      who showed an enlarged ectopic thyroid gland with a Tc-99m pertechnetate uptake
      of 2% or more. RESULTS: Of 115 neonates with ectopic thyroid glands, 19 showed an
      enlarged gland with Tc-99m uptake ranging from 2 to 3.2%. Perchlorate discharge
      test was performed in 13 of these and was consistent with iodine organification
      defect in nine. Repeated PDT in seven patients showed normal values. CONCLUSION:
      The results of the authors' study indicate the transient nature of the iodine
      organification defect and suggest that a delay in the developmental of synthetic
      mechanisms occur in the dysgenetic glands.

PMID- 8993868
TI  - Effect of gallium nitrate therapy on Ga-67 scintigraphic detection of lymphoma:
      case report.
AB  - Ga-67 and abdominal CT scans of a 72-year-old woman who had malignant lymphoma
      before, during, and after gallium nitrate/hydroxyurea combination therapy are
      presented. Disappearance of Ga-67 uptake by the tumor during this treatment
      despite continuing CT evidence of disease and reappearance of Ga-67 scan
      abnormalities after cessation of therapy suggests that caution should be
      exercised when interpreting results of Ga-67 scintigraphy for the detection of
      tumor viability during gallium nitrate/hydroxyurea therapy.

PMID- 8993867
TI  - The diagnostic value of Tc-99m human polyclonal immunoglobulin imaging compared
      to Tc-99m HMPAO labeled leukocytes in inflammatory bowel disease.
AB  - The aim of this study was to establish the usefulness of Tc-99m human polyclonal
      immunoglobulin (HIG) imaging in a group of patients who were suspected of having
      inflammatory bowel disease (IBD). The authors performed 30 scans (15 with Tc-99m
      HMPAO leukocytes and 15 with Tc-99m HIG) on 15 patients with IBD. Ten patients
      had Crohn's disease and five had ulcerative colitis. The sensitivity of Tc-99m
      HIG scintigraphy for detecting IBD was 33%, while the sensitivity of Tc-99m HMPAO
      leukocyte imaging was 100%. The Tc-99m HMPAO leukocyte imaging also detected a
      larger number of affected segments and provided better image quality of the
      extent of disease than Tc-99m HIG. On the basis of these results, the authors
      believe that Tc-99m HIG imaging is not a useful technique in the evaluation of
      patients with IBD, in the identification of location, or the extension or degree
      of disease activity.

PMID- 8993869
TI  - Radioimmunoscintigraphy in patients with ocular melanoma.
AB  - The aim of this study was to determine the usefulness of radioimmunoscintigraphy
      (RIS) with monoclonal antibodies (MAb) to detect primary ocular melanoma and its
      relapses and metastases. The authors studied nineteen patients (9 men and 10
      women), aged 24 to 74 who were suspected of having ocular pigmented tumors by
      means of RIS. The authors used F(ad)2-fragments of monoclonal antibodies against
      high molecular weight-melanoma associated antigen, labeled with Tc-99m (activity
      370-555 MBq). Planar and SPECT imaging were performed at 6, 12, and 24 hours. The
      sensitivity of the method was 78.6%; the specificity was 100%; and the accuracy
      was 84.2%. The results obtained suggest that RIS is a highly specific and
      sensitive technique in the differential diagnosis of malignant ocular melanoma.

PMID- 8993871
TI  - Liver hemangioma. A perioperative Tc-99m RBC SPECT correlation.
AB  - Scintigraphic diagnosis of a liver hemangioma may be difficult when its size
      approaches the spatial resolution of a gamma camera, and it may not be visualized
      on a Tc-99m tin-colloid liver SPECT study. The contribution of Tc-99m labeled RBC
      scintigraphy is shown in a patient with a liver hemangioma discovered during
      laparoscopic cholecystectomy for chronic cholecystitis. Despite negative CT, US,
      and Tc-99m tin-colloid SPECT of the liver, Tc-99m labeled RBC SPECT disclosed a
      focus of increased activity consistent with the hemangioma.

PMID- 8993870
TI  - Radioimmunoscintigraphy with Tc-99m labeled monoclonal antibody 170H.82 in
      suspected primary, recurrent, or metastatic breast cancer.
AB  - Radioimmunoscintigraphy (RIS) with Tc-99m labeled 170H.82, an intact murine
      monoclonal antibody (MAb) was performed in 27 patients with suspected primary,
      recurrent, or metastatic breast cancer. For radioimmunoimaging the authors used a
      double-headed, high-resolution gamma camera. The lesions detected by RIS were
      evaluated by histopathology, and for metastatic disease by CT, MRI, and bone
      scan. If the evaluation was made lesion by lesion, RIS with Tc-99m MAb 170H.82
      showed 23 true-positive results, 3 false-negative results, 9 true-negative
      results, 3 false-positive results for primary and recurrent disease; sensitivity
      was 88% and specificity was 75%. In patients with distant metastases, detection
      rate was 67% (12 true-positive results and 6 false-negative results). All
      patients had normal baseline values for human anti-mouse antibodies (HAMA) and 6
      weeks after RIS with 2 mg MAb, only 2 of 23 patients had developed a HAMA
      response (9%). No adverse effects were observed. The authors' clinical experience
      shows that RIS with MAb 170H.82 is a valuable additional method for detecting
      breast cancer, especially in patients with uncertain primaries or scar tissue
      after breast conserving treatment in which differential diagnosis is very
      difficult.

PMID- 8993863
TI  - PCR in laboratory diagnosis of human Borrelia burgdorferi infections.
AB  - The laboratory diagnosis of Lyme borreliosis, the most prevalent vector-borne
      disease in the United States and endemic in parts of Europe and Asia, is
      currently based on serology with known limitations. Direct demonstration of
      Borrelia burgdorferi by culture may require weeks, while enzyme-linked
      immunosorbent assays for antigen detection often lack sensitivity. The
      development of the PCR has offered a new dimension in the diagnosis. Capable of
      amplifying minute amounts of DNA into billions of copies in just a few hours, PCR
      facilitates the sensitive and specific detection of DNA or RNA of pathogenic
      organisms. This review is restricted to applications of PCR methods in the
      diagnosis of human B. burgdorferi infections. In the first section,
      methodological aspects, e.g., sample preparation, target selection, primers and
      PCR methods, and detection and control of inhibition and contamination, are
      highlighted. In the second part, emphasis is placed on diagnostic aspects, where
      PCR results in patients with dermatological, neurological, joint, and ocular
      manifestations of the disease are discussed. Here, special attention is given to
      monitoring treatment efficacy by PCR tests. Last, specific guidelines on how to
      interpret PCR results, together with the advantages and limitations of these new
      techniques, are presented.

PMID- 8993872
TI  - Comparison of Tc-99m pertechnetate with Tl-201 and Ga-67 scintigraphy of
      malignant soft-tissue tumors.
AB  - Tc-99m pertechnetate scintigraphy was compared with Tl-201 chloride and Ga-67
      citrate to evaluate the avidity of Tc-99m pertechtate for malignant soft-tissue
      tumors. Twenty-three patients with malignant soft-tissue tumors underwent
      scintigraphic studies. All 23 received Tc-99m and Tl-201, whereas 14 also were
      injected with Ga-67. In 21 (91%) of the 23 patients, Tc-99m accumulated
      extensively in the tumors. Tl-201 accumulated in 12 (52%) of the 23 tumors. Ga-67
      accumulated in only 5 (36%) of the 14 tumors. The avidity of Tc-99m for myxoid
      tumors was markedly different from the other two agents. Tc-99m accumulated in
      all eight myxoid tumors, while neither Tl-201 or Ga-67 showed marked accumulation
      except for one patient with increased accumulation of Tl-201. This study shows
      that Tc-99m pertechnetate has the potential to localize malignant soft-tissue
      tumors and may be useful in the evaluation of these tumors.

PMID- 8993873
TI  - Gallbladder visualization on routine lung perfusion imaging.
AB  - OBJECTIVE: Two routine lung SPECT studies showed what appeared to be uptake
      within the gallbladder. This finding was confirmed on coronal views and three
      dimensional reconstruction. There was no contamination or problem with the
      radiopharmaceutical quality control. The patients had not had any prior nuclear
      procedures. Gallbladder visualization on routine lung imaging has not been
      previously observed. The purpose of this study was to ascertain the incidence of
      gallbladder uptake and to determine a possible mechanism. METHODS: Fifty-four
      patients referred for routine lung perfusion imaging were examined. At the end of
      the lung imaging, an anterior and/or right lateral 3-5 minute view of the abdomen
      was obtained. Patients too ill for additional imaging or those with prior
      cholecystectomies were excluded. RESULTS: Nineteen of the 54 patients showed
      activity within the gallbladder. Activity within the gut, kidneys, and urinary
      bladder also were observed. CONCLUSION: Gallbladder activity after Tc-99m
      macroaggregated albumin injection for lung perfusion studies, is a fairly common
      finding.

PMID- 8993862
TI  - Current methods of laboratory diagnosis of Chlamydia trachomatis infections.
AB  - Infections caused by Chlamydia trachomatis are probably the most common sexually
      transmitted diseases in the United States. Commonly unrecognized and often
      inadequately treated, chlamydial infections can ascend the reproductive tract and
      cause pelvic inflammatory disease, which often results in the devastating
      consequences of infertility, ectopic pregnancy, or chronic pelvic pain. C.
      trachomatis infections are also known to increase the risk for human
      immunodeficiency virus infection. The obligate intracellular life cycle of C.
      trachomatis has traditionally required laboratory diagnostic tests that are
      technically demanding, labor-intensive, expensive, and difficult to access. In
      spite of these historical challenges, however, laboratory diagnosis of C.
      trachomatis has been a rapidly advancing area in which there is presently a wide
      array of commercial diagnostic technologies, costs, manufacturers. This review
      describes and compares the diagnostic methods for C. trachomatis infection that
      are currently approved for use in the United States, including the newest DNA
      amplification technologies which are yet to be licensed for commercial use.
      Issues to consider in selecting a test for purposes of screening versus diagnosis
      based on prevalence, performance, legal, social, and cost issues are also
      discussed.

PMID- 8993874
TI  - Tc-99m tetrofosmin accumulation in lung cancer and its metastases.

PMID- 8993861
TI  - Clinical microbiology of coryneform bacteria.
AB  - Coryneform bacteria are aerobically growing, asporogenous, non-partially-acid
      fast, gram-positive rods of irregular morphology. Within the last few years,
      there has been a massive increase in the number of publications related to all
      aspects of their clinical microbiology. Clinical microbiologists are often
      confronted with making identifications within this heterogeneous group as well as
      with considerations of the clinical significance of such isolates. This review
      provides comprehensive information on the identification of coryneform bacteria
      and outlines recent changes in taxonomy. The following genera are covered:
      Corynebacterium, Turicella, Arthrobacter, Brevibacterium, Dermabacter.
      Propionibacterium, Rothia, Exiguobacterium, Oerskovia, Cellulomonas,
      Sanguibacter, Microbacterium, Aureobacterium, "Corynebacterium aquaticum,"
      Arcanobacterium, and Actinomyces. Case reports claiming disease associations of
      coryneform bacteria are critically reviewed. Minimal microbiological requirements
      for publications on disease associations of coryneform bacteria are proposed.

PMID- 8993876
TI  - Vanishing vertebra.

PMID- 8993875
TI  - Simultaneous demonstration of gastrointestinal bleeding and functional femoral
      femoral graft.

PMID- 8993877
TI  - Colon visualization on a bone scan from metastatic ovarian carcinoma: SPECT
      correlation.

PMID- 8993878
TI  - Scintigraphic appearance of parosteal osteosarcoma.

PMID- 8993879
TI  - Cerebrospinal fluid fistula to the maxillary bone demonstrated by In-111 DTPA
      cisternography.

PMID- 8993880
TI  - Somatostatin receptor imaging: fatty meal-induced clearance of gallbladder
      activity.

PMID- 8993881
TI  - Lymphoscintigraphy using Tc-99m human serum albumin in chylothorax.

PMID- 8993882
TI  - Adult T-cell leukemia with invasion by malignant cells of both parotid glands
      diagnosed by an Ga-67 imaging: a case report.

PMID- 8993884
TI  - Current readings in nuclear medicine.

PMID- 8993883
TI  - Fusion or apposition? A case of a broken horseshoe kidney.

PMID- 8993935
TI  - Ischaemic episodes detected by early exercise test and Holter monitoring after
      myocardial infarction: which are of most prognostic value?
AB  - BACKGROUND: The aim of this study was to assess the significance of ST-segment
      depressions (ST-SD) detected during exercise test or Holter monitoring and to
      determine which parameters of ST-SD are the most important prognostic factors in
      patients after myocardial infarction. METHODS: The study group consisted of 164
      patients (126 men and 38 women) who survived their first uncomplicated myocardial
      infarction. Twenty-four-hour Holter monitoring on day 10 (+/- 2) after infarction
      and a treadmill exercise test 1 or 2 days later were performed. The following
      parameters of ST-SD were taken into consideration: amplitude, localization
      according to the area of infarction and presence or absence of concomitant
      angina. Patients were observed for 24 months to assess the occurrence of new
      cardiac events. RESULTS: In 78 patients (group I) ST-SD were detected in both
      Holter monitoring and the exercise test, and in 32 patients (group II) in the
      exercise test only. Fifty-four patients (group III) were without ST-SD. During
      follow-up there were 83 cardiac events in group I, 24 in group II and 16 in group
      III (P < 0.01, group I versus II; P < 0.0001, group I versus III; P < 0.05, group
      II versus III). In multivariate analysis the presence of ST-SD during Holter
      monitoring or the exercise test, or both, appeared to be of most prognostic
      significance (P < 0.0001). The number of new cardiac events was significantly
      higher in patients with painful ST-SD greater than 3 mm, detected outside the
      area of infarction (distant ischaemia). CONCLUSIONS: This study shows a
      significant prognostic value of early post-infarction ischaemia detected by
      Holter monitoring and an exercise test. Distant, painful ST-SD greater than 3 mm
      were more powerful determinants of poor prognosis than others. Electrode
      placement during Holter monitoring appears to be very important, particularly in
      post-infarction patients.

PMID- 8993936
TI  - Effects of preload on regional nonischemic end-systolic performance.
AB  - BACKGROUND: Nonischemic segmental performance, assessed by end-systolic measures
      of shortening and thickening, decreases during ischemia. These changes in
      performance are likely to be dependent on the size, and, possibly, the site of
      the ischemic zone. This study was designed to examine the effect of preload,
      independently from ischemic zone size, on nonischemic end-systolic performance.
      METHODS: Twelve beagles were instrumented with sonomicrometers and micromanometer
      pressure gauges. End-systolic pressure length and thickness relationship data
      were obtained during vena caval balloon inflation. Control data were obtained
      both in left anterior descending and in left circumflex regions at left
      ventricular end-diastolic pressures of 5, 10 and 15 mmHg. The left circumflex
      artery was occluded for 90 s and nonischemic end-systolic pressure length and
      thickness data were obtained at each diastolic pressure. A 20 min recovery period
      was allowed between coronary occlusions. RESULTS: The isovolumic bulge in the
      ischemic area was more pronounced at an end-diastolic pressure of 5 mmHg than it
      was at an end-diastolic pressure of 15 mmHg. The slope of the nonischemic end
      systolic pressure length and thickness relationships decreased at an end
      diastolic pressure of 5 mmHg, whereas at 10 and 15 mmHg the slope of these
      relationships did not change significantly. The shift in the nonischemic end
      systolic pressure-length relationship to the right was more pronounced at a low
      end-diastolic pressure (5 mmHg) than it was at a high end-diastolic pressure (15
      mmHg). Similarly, the extent of the shift in the end-systolic pressure-thickness
      relationship to the left was more marked at a low end-diastolic pressure than it
      was at the higher end-diastolic pressure. CONCLUSION: Regional ischemia decreases
      the end-systolic performance of the nonischemic region. The extent of the shift
      and the degree to which the slopes of the nonischemic end-systolic relations
      decrease are influenced by loading conditions.

PMID- 8993938
TI  - Synergistic augmentation of expression of plasminogen activator inhibitor type-1
      induced by insulin, very-low-density lipoproteins, and fatty acids.
AB  - BACKGROUND: Plasminogen activator inhibitor type-1 (PAI-1) implicated as a
      determinant of thrombosis, and possibly of atherosclerosis, is increased
      approximately four-fold in the blood of subjects with type II diabetes, and the
      increase is closely correlated with concentrations of insulin. Insulin can
      stimulate expression of PAI-1 in vitro, but infusions of insulin in human
      subjects have not increased PAI-1 in blood in acute, euglycemic clamp studies.
      OBJECTIVE: To determine whether the dichotomy reflects interactions between
      insulin and both very-low-density lipoprotein (VLDL)-bound triglycerides (VLDL
      TG) and albumin-bound nonesterified (free) fatty acids (FFA) affecting PAI-1
      elaboration. METHODS: HepG2 cells (human hepatoma cell line) were exposed to
      insulin, VLDL, and FFA alone and in selected combinations for 24 h. RESULTS:
      Striking synergistic effects were observed. Thus, compared with control,
      pathophysiologic concentrations of insulin increased PAI-1 accumulation in
      conditioned media modestly, as did VLDL, but the combination elicited a marked
      nine-fold increase (control PAI-130 +/- 2 ng/ml, PAI-1 with 400 mg/dl VLDL-TG 97
      +/- 6 ng/ml; with 4 nmol/1 insulin 45 +/- 6 ng/ml, with 400 mg/dl VLDL-TG plus 4
      nmol/1 insulin 276 +/- 47 ng/ml; P < 0.01 for the combination compared with
      control or with either agent alone). Similarly, a modest increase was found
      either with insulin or with FFA alone, but a synergistic increase was evident
      when they were combined (control 27 +/- 3 ng/ml; 1 mmol/l FFA 36 +/- 2 ng/ml; 10
      nmol/l insulin 59 +/- 6 ng/ml; 1 mmol/l FFA plus 10 nmol/l insulin 82 +/- 1
      ng/ml; P < 0.01 for the combination compared with control or with either agent
      alone). CONCLUSION: The combination of increased insulin with elevated VLDL-TG
      and increased FFA appears to cause the increase in PAI-1 in blood of subjects
      with type II diabetes mellitus and other insulin-resistant states, providing
      novel and promising targets for normalizing altered fibrinolytic system potential
      and thereby ameliorating the associated predisposition to persistent thrombosis
      and possibly atherosclerosis.

PMID- 8993937
TI  - Death, mode of death, morbidity and requirement for rehospitalization during 2
      years after coronary artery bypass grafting in relation to preoperative ejection
      fraction.
AB  - OBJECTIVE: To describe the impact of ejection fraction on the prognosis during 2
      years after coronary artery bypass grafting (CABG). PATIENTS: All patients in
      western Sweden who underwent CABG without concomitant valve surgery between June
      1988 and June 1991. RESULTS: In all, 2121 patients were operated upon and
      information on ejection fraction was available for 1961 patients (92%). Of these
      patients, 178 (9%) had an ejection fraction < 40%, 517 (26%) an ejection fraction
      of 40-59% and 1266 (65%) an ejection fraction > or = 60%. In these groups the
      mortalities during the first 30 days after CABG were 5.1, 4.3 and 2.2%,
      respectively (P < 0.01). The corresponding values for mortalities between 30 days
      and 2 years were 7.7, 4.3 and 3.3%, respectively (P < 0.01). Patients with a
      lower ejection fraction were more frequently men and more frequently had a
      history of cardiovascular disease. In multivariate analysis the preoperative
      ejection fraction was an independent predictor for total 2-year mortality.
      Patients with a low ejection fraction died more frequently in association with
      ventricular fibrillation. Morbidity was, with the exception of that for
      rehospitalization due to heart failure and infection, not associated
      significantly with the preoperative ejection fraction. CONCLUSION: During the 2
      years after CABG a low preoperative ejection fraction was associated with a
      higher mortality, but the association with morbidity was more complex.

PMID- 8993940
TI  - The cardiac health profile: content, reliability and validity of a new disease
      specific quality of life questionnaire.
AB  - BACKGROUND: The Cardiac Health Profile (CHP) is a new questionnaire for assessing
      health-related quality of life of patients with cardiovascular diseases. It
      consists of three parts assessed as follows: the degree of angina pectoris (the
      CCS scale), the quality of life and subjective scoring of psychosocial 'cost
      benefit'. Parts II and III of the questionnaire are based on visual analogous
      scales and consist of 16 and two questions, respectively, covering nine areas.
      This quality of life questionnaire has been tested for reliability, validity and
      sensitivity. METHODS: Eighty consecutive patients with angina pectoris, who were
      waiting for coronary angiography, were enrolled in the study. Four sets of data
      were deleted since the respondents were not able to fill in the forms correctly.
      Fifty-one healthy volunteers constituted a control group. RESULTS: Reliability
      was assessed by a 'test and retest' method. The resulting correlation coefficient
      was 0.927 (P = 0.0009). Internal consistency was studied by applying Cronbach's
      alpha. The internal alpha-coefficient was 0.89. Concurrent validity was studied
      by comparing the outcome in the Nottingham Profile with the CHP. The
      intercorrelation indicated good concurrent validity (r = 0.753, P = 0.0001). The
      construct validity was assessed by performing a factor analysis. The sensitivity
      was assessed in three ways: analysis of kurtosis, comparison of the group of
      angina pectoris patients with a healthy control group and by comparing CHP
      results before a standard intervention (coronary artery bypass grafting) and
      after. The CHP showed in all of these ways a good sensitivity with statistically
      significant differences between angina patients and the control group (P <
      0.0001). A significant improvement in health-related quality of life was also
      found after coronary artery bypass grafting compared with before (P = 0.02).
      CONCLUSIONS: The CHP has been found to be reliable, valid and sensitive and the
      present findings encourage use of the questionnaire in clinical trials for its
      further development.

PMID- 8993939
TI  - Exercise-induced coronary spasm: comparison of treadmill and bicycle exercise in
      patients with vasospastic angina.
AB  - BACKGROUND: We investigated whether exercise-induced coronary spasms are
      influenced by the different exercise modes. METHODS: We compared ischaemic ECG
      responses in 67 patients with vasospastic angina who underwent both treadmill and
      bicycle ergometer exercise and also coronary angiography. RESULTS: ECG ST-segment
      elevation was provoked more frequently during treadmill exercise than it was
      during bicycle exercise (19 versus 9%, P < 0.05). Of 45 patients without
      significant coronary stenosis (coronary artery luminal diameter narrowing < 75%),
      19 patients manifested ST-segment depression during treadmill exercise, whereas
      only seven patients did during bicycle exercise (42 versus 16%, P < 0.01). All
      patients with ST-segment elevation or depression during bicycle ergometer
      exercise also had ST-segment changes during treadmill exercise. Although higher
      systemic blood pressure levels and lower heart rates were found during bicycle
      exercise compared with during treadmill exercise the pressure-rate products at
      peak exercise did not differ between the two exercise tests. CONCLUSIONS: It
      seems that treadmill and bicycle exercise are different stressors in patients
      with vasospastic angina, and that coronary spasms are provoked more frequently
      during treadmill exercise than they are during bicycle exercise. The cause of
      this difference is not known, but it may be related in part to the difference in
      systemic haemodynamic or neurohumoral response.

PMID- 8993941
TI  - Comparative diagnostic value of dobutamine stress echocardiography and stress
      thallium-201 single-photon-emission computed tomography for detecting coronary
      artery disease in women.
AB  - BACKGROUND: The non-invasive diagnosis of coronary artery disease in women
      remains a difficult clinical problem. The aim of this study was to investigate
      the comparative diagnostic accuracy of dobutamine stress echocardiography and
      stress thallium-201 single-photon-emission computed tomography (SPECT) in women
      who were suspected to have coronary artery disease. METHODS: We studied 70
      consecutive women who had not had a previous myocardial infarction (mean age 65
      years) who underwent dobutamine stress echocardiography and quantitative coronary
      angiography. Sixty-one of the 70 women were also subjected to thallium-201 SPECT,
      with exercise or dipyridamole administration as the stressor, during the same
      period. A positive diagnosis was based on the detection of inducible wall motion
      abnormality and the presence of stress-induced abnormalities of perfusion.
      RESULTS: No significant complication occurred in any patient during dobutamine
      stress echocardiography (peak dose 31 +/- 9 micrograms/kg per min, atropine
      administered to 13 patients, peak heart rate 120 +/- 19 beats/min). Coronary
      artery disease (> or = 50% diameter stenosis) was present in 20 (29%) patients,
      nine with one-vessel and 11 with multivessel disease. The sensitivity,
      specificity and diagnostic accuracy of dobutamine stress echocardiography for
      detecting coronary artery disease were 75, 92 and 87% respectively. In 61
      patients who underwent both stress tests, the sensitivity, specificity and
      accuracy of dobutamine stress echocardiography and stress thallium-201 SPECT were
      72 versus 78%, 91 versus 70% (P < 0.05) and 85 versus 72%, respectively.
      CONCLUSIONS: Dobutamine stress echocardiography appears to be of comparable
      sensitivity and higher specificity with stress thallium-201 SPECT for noninvasive
      detection of coronary artery disease in women.

PMID- 8993942
TI  - Effect of purified eicosapentaenoate ethyl ester on fibrinolytic capacity in
      patients with stable coronary artery disease and lower extremity ischaemia.
AB  - BACKGROUND: Lower extremity ischaemia is often complicated by coronary artery
      disease (CAD). Patients with CAD often have impaired fibrinolytic capacity.
      Plasma plasminogen activator inhibitors (PAI) levels are known to be associated
      with levels of atherogenic lipids. Purified eicosapentaenoic acid reduces
      atherogenic lipid levels. OBJECTIVE: To examine the effect of purified
      eicosapentaenoic acid ethyl ester (EPA) on the fibrinolytic capacity in patients
      with stable CAD and arteriosclerosis obliterans (ASO). METHODS: Plasma levels of
      PAl activity and tissue-type plasminogen activator (t-PA) antigen were measured.
      We administered 1800 mg/day EPA for 8 weeks to 25 patients. RESULTS: Mean
      baseline plasma PAI activity (P < 0.01) and t-PA antigen (P < 0.01) levels were
      higher in the patient group than they were in the control group. At the
      conclusion of EPA administration, significant reductions in PAI activity (P <
      0.01), t-PA antigen (P < 0.01) and serum levels of triglyceride (P < 0.01), total
      (P < 0.05) and low-density lipoprotein (P < 0.05) cholesterols were observed.
      Changes in PAI activity levels caused by EPA administration showed positive
      linear correlations with those in low-density lipoprotein cholesterol (r = 0.411,
      P < 0.05) and triglyceride (r = 0.652, P < 0.01). CONCLUSION: These findings
      indicate that the fibrinolytic capacity in patients with CAD and ASO is decreased
      by increased PAI activity, but that EPA may correct this fibrinolytic impairment
      by decreasing PAI activity via its inhibitory effect on atherogenic lipids.

PMID- 8993945
TI  - Bibliography current world literature.

PMID- 8993944
TI  - Inhibition of coronary restenosis by antithrombin III in atherosclerotic swine.
AB  - BACKGROUND: Thrombin-mediated vascular smooth muscle cell proliferation has been
      implicated in coronary restenosis. Attempts to inhibit this mitogenic activity
      have recently focused on non-physiologic direct thrombin inhibitors, whereas
      endogenous thrombin inhibitors such as antithrombin III (ATIII) have received
      little attention. ATIII is the main physiologic inhibitor of thrombin and may
      thus be a potential therapeutic agent for prevention of restenosis. METHODS:
      Human ATIII (125 U/kg) and heparin (200 U/kg) were administered to 12
      atherosclerotic swine 30 min prior to inducing restenosis by oversized stent
      (left anterior descending and right coronary arteries; stent-to-artery ratio
      approximately 1.2) and balloon injury (circumflex; balloon artery ratio
      approximately 1.2). Eleven control swine received only heparin every 6 h for 24 h
      and were subjected to similar stent and balloon injury. Quantitative coronary
      angiography [change in minimal lumen diameter (delta MLD)] and morphometric
      analysis [percentage area stenosis (PAS)] were performed 4 weeks later. RESULTS:
      ATIII activity (mean +/- SD) of treated swine increased from a baseline of 103 +/
      10% to a peak of 266 +/- 48%, whereas trough levels were maintained at 259 +/-
      55% for 72 h by drug infusions every 6 h. The delta MLD, the primary angiographic
      endpoint in the balloon injured vessel was -0.57 +/- 0.33 mm in heparin group
      versus -0.26 +/- 0.27 mm in the ATIII group (P < or = 0.03). For stented vessels
      the delta MLD was -0.61 +/- 0.33 mm in the heparin group versus -0.41 +/- 0.37 mm
      in the ATIII group (P < or = 0.06). The PAS for the balloon injured vessels was
      30 +/- 12% in the heparin group versus 19 +/- 14 in the ATIII group (P < or =
      0.06). In stented vessels the PAS was 45 +/- 16% in the heparin group versus 38
      +/- 16% in the ATIII group (P < or = 0.1). CONCLUSION: Supraphysiologic ATIII
      levels in combination with heparin inhibits the reduction in MLD in coronary
      arteries subjected to oversized balloon injury and demonstrates a beneficial
      trend in arteries subjected to oversized stent injury. These data provide
      cautious optimism for further investigation with ATIII to prevent coronary
      restenosis.

PMID- 8993943
TI  - Effects of simvastatin and ciprofibrate alone and in combination on lipid
      profile, plasma fibrinogen and low density lipoprotein particle structure and
      distribution in patients with familial combined hyperlipidaemia and coronary
      artery disease.
AB  - BACKGROUND: Hypolipidaemic agents do not usually normalize all of the multiple
      lipoprotein abnormalities in patients with familial combined hyperlipidaemia
      (FCHL). The effect of the simvastatin-ciprofibrate combination in comparison with
      each drug alone on the lipoprotein abnormality patterns was studied in patients
      with FCHL and coronary artery disease (CAD). METHODS: Sixty patients (53 men and
      seven women), mean age 52 years (range 36-60 years), were studied. After a 4-week
      placebo period, patients were randomly assigned to three groups. The first group
      (n = 20) received simvastatin (20 mg daily), the second group (n = 20)
      ciprofibrate (100 mg daily) and the third group (n = 20) the combination of both
      drugs for a 12-week period. Parameters measured were as follows: plasma
      fibrinogen, total cholesterol, triglycerides, low density lipoprotein (LDL), very
      low density lipoprotein, intermediate density lipoprotein, and high density
      lipoprotein cholesterol, as well as LDL subfraction distribution and structure by
      density gradient ultracentrifugation. Apoproteins (apo) B and AI were assessed by
      immunoturbidometry. RESULTS: At baseline, apoB, LDL cholesterol and triglycerides
      were increased, whereas LDL particles were small and dense. ApoB was
      significantly reduced by all three interventions. Drug combination and
      ciprofibrate significantly reduced plasma fibrinogen (-24 and -25%, respectively;
      P < 0.001) and triglycerides (-51 and -49%, respectively; P < 0.001). Drug
      combination and simvastatin significantly reduced LDL cholesterol (-25 and -22%,
      respectively; P < 0.001) compared with ciprofibrate (-10%; P < 0.01).
      Ciprofibrate and drug combination increased LDL particle size (parameter K -0.24
      versus -0.61 and -0.30 versus -0.62, respectively; P < 0.001), whereas
      simvastatin had no significant effect on LDL particle size. The cholesterol
      content of LDL particles was reduced with ciprofibrate and the drug combination
      only in the dense LDL particles (LDL3-5) and increased in the light (LDL1-2)
      subfractions, whereas simvastatin reduced the cholesterol content of all LDL
      subfractions except LDL2. Ciprofibrate and drug combination reduced the
      triglyceride content of all LDL subfractions. CONCLUSION: Combined treatment with
      simvastatin and ciprofibrate effectively reduced plasma fibrinogen,
      triglycerides, total and LDL cholesterol and increased LDL particle size in
      patients with FCHL and CAD. These effects might induce a clinical benefit for
      these patients.

PMID- 8993860
TI  - Infections in solid-organ transplant recipients.
AB  - Solid-organ transplantation is a therapeutic option for many human diseases.
      Infections are a major complication of solid-organ transplantation. All
      candidates should undergo a thorough infectious-disease screening prior to
      transplantation. There are three time frames, influenced by surgical factors, the
      level of immunosuppression, and environmental exposures, during which infections
      of specific types most frequently occur posttransplantation. Most infections
      during the first month are related to surgical complications. Opportunistic
      infections typically occur from the second to the sixth month. During the late
      posttransplant period (beyond 6 months), transplantation recipients suffer from
      the same infections seen in the general community. Opportunistic bacterial
      infections seen in transplant recipients include those caused by Legionella spp.,
      Nocardia spp., Salmonella spp., and Listeria monocytogenes. Cytomegalovirus is
      the most common cause of viral infections. Herpes simplex virus, varicella-zoster
      virus, Epstein-Barr virus and others are also significant pathogens. Fungal
      infections, caused by both yeasts and mycelial fungi, are associated with the
      highest mortality rates. Mycobacterial, pneumocystis, and parasitic diseases may
      also occur.

PMID- 8993946
TI  - The leaking esophagus: CT patterns of esophageal rupture, perforation, and
      fistulization.
AB  - Esophageal perforation can be a catastrophic event for a patient regardless of
      the etiology of the perforation. Contrast esophagrams can typically diagnose an
      esophageal perforation if the clinical symptoms or history suggest the diagnosis.
      Often, however, the clinical features are atypical and a CT scan is performed
      early in the patient's workup. It is, therefore, essential to recognize the CT
      features seen in esophageal perforation. The various etiologies and CT findings
      of esophageal perforation are reviewed in this article. The CT abnormalities
      include extraluminal air, periesophageal fluid, esophageal thickening, and
      extraluminal contrast. These CT findings may be the first clue to the correct
      diagnosis of esophageal perforation.

PMID- 8993947
TI  - Pulmonary aspergillosis: a spectrum of disease.
AB  - Although many species of the fungus Aspergillus have been identified, the most
      common human pathogen is A. fumigatus, which has a worldwide distribution.
      Although any organ may become infected, pulmonary aspergillosis is the most
      common manifestation. The spectrum of pulmonary aspergillosis includes
      saprophytic aspergillomas, allergic bronchopulmonary aspergillosis, chronic
      necrotizing aspergillosis, and invasive aspergillosis. Immune status of the host,
      and the presence of underlying lung disease are important in determining the type
      of pulmonary involvement. Thus, the radiographic findings are variable. This
      article reviews the various manifestations of pulmonary aspergillosis, including
      the immune status of the patient, the presence of underlying lung disease, and
      the radiographic appearance of the different entities.

PMID- 8993948
TI  - The quandary of climacteric skin ageing.

PMID- 8993949
TI  - Angiokeratomas: an update.
AB  - Angiokeratomas are vascular lesions which are defined histologically as one or
      more dilated blood vessel(s) lying directly subepidermal and showing an epidermal
      proliferative reaction. At the center of pathogenesis there is a capillary
      ectasia in the papillary dermis. The epidermal changes in all forms of
      angiokeratoma are secondary. The different entities causing vessel ectasia lead
      to the many clinical variants of angiokeratoma. Current classification
      distinguishes between widespread forms (angiokeratoma corporis diffusum), which
      is usually associated with an inborn error of metabolism, and localized forms,
      which include solitary angiokeratoma, Fordyce's angiokeratoma, angiokeratoma
      circumscriptum naeviforme and angiokeratoma of Mibelli.

PMID- 8993950
TI  - Investigation of skin-derived lymph: an approach to get insight into the skin
      immune system.
AB  - The skin acts as a mechanical, physicochemical and immunological control and
      defense system, and its lymphatic vessels play a role in the regulation of cell
      hydration and osmosis, as well as in immunological responses. Skin-derived
      signals, produced in response to various agents acting on the skin, arrive with
      the afferent lymph at the regional lymph nodes. These signals reflect the
      immunological processes in the skin and may also determine the reactions in the
      lymph node. By analyzing afferent lymph derived from specific skin lesions it
      should therefore be possible to get insight into local pathomechanisms as well as
      the signal transmission in skin disorders. In this report, we present
      methodological aspects of such skin-derived lymph studies and review the results
      obtained from studies of sodium-lauryl-sulfate-induced irritative contact
      dermatitis in humans.

PMID- 8993951
TI  - Does hormonal skin aging exist? A study of the influence of different hormone
      therapy regimens on the skin of postmenopausal women using non-invasive
      measurement techniques.
AB  - BACKGROUND AND DESIGN: The skin properties of 98 postmenopausal women with
      hormone replacement therapy (oestradiol gel or patches) or without hormone
      replacement therapy were studied using non-invasive techniques: skin thickness
      with skin echography, skin hydration with a dryness score and measurement of
      capacitance, skin surface lipids with a Sebumeter and microtopography with image
      analysis of cutaneous replicas. RESULTS: In this open study we demonstrated an
      increase in skin thickness and sebum in the treated group in comparison to the
      untreated group (7-15% according to area for skin thickness, 35% for sebum).
      Hydration and microtopography were not different in the two groups. CONCLUSIONS:
      Postmenopausal women who were receiving hormonal substitution have a greater
      thickness and casual level than untreated women. We therefore suggest that
      hormonal aging exists and that cutaneous atrophy can be prevented with hormone
      replacement therapy.

PMID- 8993952
TI  - Psoriatic arthritis and hypopyon-iridocyclitis. Possible mechanism of the
      association of psoriasis and anterior uveitis.
AB  - BACKGROUND: We present a 32-year-old Japanese man with psoriatic arthritis who
      developed recurrent episodes of hypopyon-iridocyclitis associated with
      exacerbations of the arthropathy. OBJECTIVE: To evaluate the mechanism of the
      association between psoriasis and uveitis, we analyzed the rheological
      characteristics of the patient's peripheral blood neutrophils during attacks and
      during remissions. METHODS: The rheological activity of neutrophils was
      determined by the micropore filtration method. It was expressed as micropore
      filtration time when a neutrophil-erythrocyte suspension passes through a
      micropore filter (pore size 5 microns). RESULTS: The micropore filtration time in
      this patient was longer than that of healthy control subjects (p < 0.01) and of
      psoriatic patients without uveitis (p < 0.05); it was also longer during the
      appearance of the eye disorder with the exacerbation of psoriatic arthritis than
      during remissions. CONCLUSIONS: Activated neutrophils in the peripheral blood of
      our patient were probably responsible for the attacks of hypopyon-iridocyclitis
      as well as the exacerbation of psoriatic skin lesions and/or arthritis.

PMID- 8993953
TI  - Psoriasis of the nails associated with disability in a large number of patients:
      results of a recent interview with 1,728 patients.
AB  - BACKGROUND AND OBJECTIVE: Occurrence rates of clinical features of nail psoriasis
      vary considerably in the literature. Little information is available on
      subjective complaints of patients affected by psoriasis of the nails. METHOD:
      Interviews with 1,728 psoriatic patients concerning their nail changes and
      complaints are reviewed. RESULTS: The results indicate that pitting and
      deformation are the most common clinical aberrations in psoriatic nails, with a
      positive association between the duration of skin lesions and nail psoriasis. No
      relation was found between age and nail psoriasis in this group. Remarkably,
      51.8% of patients suffered from pain-caused by the nail changes, and a large
      group of patients was restricted in their daily activities, housekeeping and/or
      profession (58.9, 56.1, 47.9%). Treatment was disappointing: only 19.3% showed
      marked improvement during treatment. CONCLUSION: This indicates that psoriasis of
      the nails is a more important individual and social-economic problem than
      previously assumed and that development of new treatments is needed.

PMID- 8993954
TI  - Dimensions of stigmatization in patients with psoriasis in a "Questionnaire on
      Experience with Skin Complaints'.
AB  - BACKGROUND: Stigmatization is a central experience of patients with psoriasis
      with a broad psychic and social impact. OBJECTIVE: The purpose of this study is
      to identify the dimensions of stigma experience by a Questionnaire on Experience
      with Skin Complaints (QES; 'Fragebogen zum Erleben von Hautbeschwerden').
      METHODS: 187 in-patients with psoriasis were examined with the QES, an adopted
      and extended (German) version of the Feeling of Stigmatization Questionnaire by
      Ginsburg and Link. A factor analysis of the questionnaire was conducted and the
      construct validity was evaluated. RESULTS: Five factors were found: 'self
      esteem', 'retreat', 'rejection', 'composure' and 'concealment'. Self-esteem,
      retreat and rejection are mainly influenced by 'problematic regions' affected by
      psoriasis, rejection also by 'visible parts' and retreat also by 'invisible
      regions'. The influences of age, age at onset and sex on the stigma experience
      are small but significant. CONCLUSIONS: The QES proved to be an economical and
      reliable psychometric instrument to differentiate the stigma experience of
      psoriasis patients.

PMID- 8993955
TI  - Enhancing effect of ultraviolet A on ornithine decarboxylase induction and
      dermatitis evoked by 12-o-tetradecanoylphorbol-13-acetate and its inhibition by
      curcumin in mouse skin.
AB  - BACKGROUND: Previous studies have demonstrated appreciable tumor induction in
      mouse skin by daily irradiation with high-power long-wavelength ultraviolet A
      (UVA). OBJECT: The aim of the present study was to examine the enhancing effects
      of UVA on changes in mouse skin mediated by the tumor promoter 12-o
      tetradecanoylphorbol-13-acetate (TPA) by measurement of ornithine decarboxylase
      (ODC) activity and morphometric analysis. In addition, we examined the inhibitory
      effects of curcumin, a component of turmeric, on these changes. METHOD: ODC
      activity in the epidermis of CD-1 mice was determined by the method of Russell
      and Snyder. Epidermal and dermal thickness, and the number of dermal infiltrating
      inflammatory cells were quantified using a computer-assisted image analyzer.
      RESULTS: A combination of topical TPA application and UVA irradiation produced a
      greater increment of ODC activity at 4 h than TPA alone (p < 0.05).
      Histopathologically, TPA plus UVA tended to increase the dermal infiltrating
      inflammatory cells in contrast to TPA alone. Pretreatment of mice with curcumin
      significantly abrogated the TPA-induced changes in ODC activity and the dermal
      infiltrating inflammatory cells as well as the TPA plus UVA-mediated enhancement
      of these changes. CONCLUSION: Our data indicate that UVA irradiation (18.72
      J/cm2) significantly enhances ODC induction at an early stage (4-6 h) after
      topical application of TPA, and aggravates the dermatitis elicited by TPA.
      Pretreatment with curcumin significantly inhibits these enhancing effects.

PMID- 8993956
TI  - Homoeopathic versus placebo therapy of children with warts on the hands: a
      randomized, double-blind clinical trial.
AB  - BACKGROUND: Despite the wide practical application of homoeopathy, scientific
      proof of its effectiveness and mechanisms is still lacking, and sound, placebo
      controlled studies are scarce. OBJECTIVE: The purpose of our study was to
      evaluate the efficacy of homoeopathy in a prospective, double-blind randomized
      trial. METHODS: 60 children aged 6-12 years with common warts on the back of the
      hands were treated either with an individually selected homoeopathic preparation
      (n = 30) of at least a 1:1,012 dilution or with pure placebo in the form of
      saccharose globuli (n = 30) under double-blind conditions. The area occupied by
      warts was measured by computerized planimetry before and after 8 weeks of
      treatment. Reduction of the warty area by at least 50% was considered a response.
      RESULTS: There were a total of 16 responders: 9 of 30 patients in the
      homoeopathic therapy group and 7 of 30 patients in the placebo group (chi 2 =
      0.34, p = 0.56). Total cure of warts occurred in 5 patients in the treated group
      and in 1 patient in the placebo group (chi 2 = 1.46, p = 0.22). CONCLUSION: There
      was no apparent difference between the effects of homoeopathic therapy and
      placebo in children with common warts under the conditions of this study.

PMID- 8993957
TI  - Thalidomide and recurrent aphthous stomatitis: a follow-up study.
AB  - BACKGROUND: Thalidomide is used for the symptomatic treatment of recurrent
      aphthous stomatitis (RAS). Some authors reported remissions, but this was not
      evaluated. OBJECTIVE: To evaluate the number of patients who could stop or reduce
      thalidomide treatment. METHODS: Twenty-five patients with RAS treated with
      thalidomide and followed during at least 1 year were retrospectively studied.
      RESULTS: Six patients could stop the treatment and further presented minor
      aphthae, 10 needed minimal daily doses of thalidomide and 7 did not respond to
      100 mg daily. One patient was not evaluated because of an early side effect and
      one was lost to follow-up. CONCLUSION: This study showed that a minority of
      patients responded and could stop thalidomide therapy whereas another group of
      patients could be maintained in remission with low doses of thalidomide which may
      represent a means to reduce the potentially severe side effects.

PMID- 8993959
TI  - Distribution of HLA class II alleles in Korean patients with epidermolysis
      bullosa acquisita.
AB  - The distribution pattern of HLA class II alleles in 12 Korean patients with
      epidermolysis bullosa acquisita was examined. The major difference in the allelic
      frequency comparing with the controls was a higher DRB1*13 allele with these
      patients (p = 0.066).

PMID- 8993958
TI  - Double-blind crossover study of high-dose cetirizine in cholinergic urticaria.
AB  - BACKGROUND: Cholinergic urticaria does not respond well to treatment with
      conventional antihistamines and is difficult to study because of its highly
      variable clinical expression which depends on the presence of eliciting factors.
      OBJECTIVE: We have therefore designed a double-blind, crossover, placebo
      controlled trial, with a 3-week treatment period using either 20 mg/day of
      cetirizine or placebo. METHODS AND RESULTS: Presence of eliciting factors and
      symptoms were scored daily on a diary card by the patient, with a scale from 0 to
      3 for erythema, wheals and pruritus. Statistical analysis was done on 11
      evaluable patients during the last 2 weeks of each treatment period (to allow for
      1 week of washout) and only for days when eliciting factors were present.
      Compared to placebo, cetirizine caused a statistically significant reduction of
      wheals (p = 0.015), erythema (p = 0.033), pruritus (p = 0.006) and all symptoms
      (p = 0.013). No adverse events were observed. CONCLUSION: These data show a high
      efficacy of cetirizine at twice its normally recommended dose which may be
      related to the specific antiallergic effects of this newer-generation
      antihistamine.

PMID- 8993960
TI  - Granulomatous mycosis fungoides presenting as sarcoidosis.
AB  - This report describes the case of a woman who developed cutaneous granulomatous
      infiltration during childhood that was initially considered to be sarcoidosis
      and, after 27 years of evolution, was determined to be caused by granulomatous
      mycosis fungoides transforming to Ki-1-positive anaplastic large-cell lymphoma of
      T-cell type. We discuss the differential diagnosis, especially granulomatous
      slack skin and the interest of immunohistochemical and genotypic studies in this
      case.

PMID- 8993961
TI  - Hepatoerythropoietic porphyria: relationship with familial porphyria cutanea
      tarda.
AB  - Hepatoerythropoietic porphyria is characterized by an early beginning of severe
      photosensitivity, with an increase in urinary uroporphyrin excretion and other
      porphyrins, high isocoproporphyrin fecal levels and an accumulation of
      protoporphyrin in erythrocytes. It is caused by a dramatic decrease in the
      activity of the uroporphyrinogen decarboxylase. We report a clinical, biochemical
      and enzymatic study in a family, where a 2-year-old girl suffers from a
      hepatoerythropoietic porphyria, and the patient's maternal uncle from a porphyria
      cutanea tarda. We discuss the relationship between these diseases and their known
      mutations.

PMID- 8993962
TI  - Erythema gyratum repens: another case of a rare disorder but no new insight into
      pathogenesis.
AB  - Erythema gyratum repens (EGR) is an uncommon but distinctive dermatosis
      characterized by marble-like swirls of erythema and a thin covering scale over
      the trunk, axillae and groins which has been associated with malignancy.
      Bronchial carcinoma has been the most frequent neoplasm associated. A case of EGR
      in a 50-year-old man with carcinoma of the lung is reported. The onset of
      dermatosis preceded the discovery of the neoplasm by 9 months. Oral
      corticosteroids induced the disappearance of the skin lesions. No recurrence was
      observed after discontinuation of the treatment. The patient died 1 year after
      the onset of dermatosis.

PMID- 8993963
TI  - Acute generalized exanthematous pustulosis induced by paracetamol. A case with
      severe hemodynamic disturbances.
AB  - We report on a 28-year-old Bangladesh man with acute generalized exanthematous
      pustulosis, induced by paracetamol. The patient presented with an erythematous
      and pustular eruption after taking 1 tablet of paracetamol for a sore throat.
      After intravenous administration of propacetamol hydrochloride (which is a
      prodrug of paracetamol), the rash became worse, showing a toxic epidermal
      necrolysis-like appearance and the patient suffered from severe hemodynamic
      disturbances. After discontinuation of propacetamol hydrochloride, the eruption
      cleared within 2 days. Prick testing performed in the patient revealed a positive
      reaction for propacetamol hydrochloride.

PMID- 8993964
TI  - Cutaneous alternariosis: role of corticosteroid-induced cutaneous fragility.
AB  - Alternaria is a very common and saprophytic fungus. Cutaneous infection is rare
      and about 71 cases have been described, mainly in Europe in immunocompromised
      hosts. We report a case of dermal alternariosis occurring in a woman treated with
      corticosteroids for dermatomyositis. The cutaneous lesion consisted of an
      erythematous and scaly plaque on the leg measuring 2 x 2 cm. Cutaneous biopsy
      showed hyphae and round inclusions stained with PAS and Gomori-Grocott within a
      polymorphous granuloma. Cultures of cutaneous biopsies grew Alternaria sp. HIV1
      and HIV2 serology was negative. The patient was treated by local excision and
      corticosteroids were decreased. One-year follow-up showed no recurrence.
      Cutaneous alternariosis is an opportunistic infection. the disease has been
      described mainly in patients treated with systemic corticosteroids (39 cases out
      of the 71 reported cases) or local corticosteroids (3/71) and in patients
      suffering from Cushing's syndrome (7/71) but rarely in HIV-infected patients
      (3/71). Cutaneous fragility induced by hypercorticism is an important cofactor
      permitting direct inoculation from the environment.

PMID- 8993965
TI  - Linear atrophoderma of Moulin: treatment with Potaba.
AB  - Linear atrophoderma is a rare disease, first described by Moulin in 1992 in 5
      patients, clinically characterized by hyperpigmented, depressed band-like areas
      along Blaschko's lines. To date, the disease has no effective treatment. We
      report the seventh case of this condition in a 16-year-old girl and discuss
      clinical and histopathologic findings, emphasizing the benefit of the potassium
      aminobenzoate (Potaba) treatment which provided an early stabilization of the
      skin lesions.

PMID- 8993966
TI  - 'Scleroedeme genito-sus-pubien' of the newborn: a forgotten disease?
AB  - A 2-month-old boy with an important hardening of the skin in the pubic and
      genital regions is presented. He was born prematurely at 31 weeks of gestation,
      and required a respirator during the first 72 h. The analytical explorations and
      abdominal ultrasound images were normal. Histological study had not shown
      significant changes. The patient did not receive any treatment and gradually
      experienced remission. Because of the location and spontaneous regression in a
      few months, the picture is very similar to the one described by Degos as
      'Scleroedeme genito-sus-pubien' of the newborn.

PMID- 8993967
TI  - Trichorhinophalangeal syndrome type III.
AB  - Trichorhinophalangeal syndrome (TRPS) type III is a newly defined clinical
      entity. This symptom complex is inherited as an autosomal dominant trait and
      clinically characterized by growth retardation, craniofacial abnormalities,
      severe brachydactyly and sparse hair. In addition, absence of mental retardation
      and cartilaginous exostoses are required for the diagnosis of TRPS III. To
      further delineate this newly recognized entity, we report on a patient from a
      Turkish family segregating TRPS III in 7 family members. The patient had a very
      short stature (147 cm, < 3rd standard deviation), a thin upper lip and a
      prominent lower lip, a pear-shaped nose, stubby fingers and toes with cone-shaped
      epiphyses and sparse scalp hair. Scanning electron microscopy findings and
      results of energy-dispersive X-ray microanalysis are presented in such a patient
      for the first time.

PMID- 8993968
TI  - Superficial spreading melanoma resembling Spitz nevus on the plantar surface.

PMID- 8993969
TI  - Subungual exostosis of a finger resembling pterygium inversum unguis.

PMID- 8993970
TI  - Bee-sting granulomas in the skin.

PMID- 8993971
TI  - Meleda disease: report of two cases investigated by electron microscopy.
AB  - We report 2 cases of clinically typical Meleda disease in a family from
      Herzegovina. Electron microscopy did not reveal major ultrastructural anomalies
      of keratinization; however, the transition from stratum granulosum to stratum
      corneum appeared to occur less abruptly than normally by a stepwise process
      suggesting a slowing down of terminal cornification.

PMID- 8993972
TI  - Acrodermatitis enteropathica secondary to Crohn's disease.
AB  - A patient suffering from Crohn's disease (CD) presented with alopecia, eczematoid
      and psoriasiform lesions located on the extremities, around the orifices and at
      pressure points, suggesting acrodermatitis enteropathica. Lately, her
      inflammatory bowel disease had flared up with abdominal pain, diarrhea and weight
      loss related to a retroperitoneal abscess. Acrodermatitis enteropathica due to
      zinc deficiency is a well-known complication of CD. In our patient the
      etiological factors involved appeared to be multiple.

PMID- 8993973
TI  - Precipitating factors and associated diseases in 84 patients with granuloma
      annulare: a retrospective study.
AB  - In a retrospective study including 84 patients, we assessed precipitating factors
      of granuloma annulare (GA) and associated pathologies. Fifteen per-cent of the
      patients reported stress as an important trigger of GA, and in 10 patients (12%)
      we found an association between GA and diabetes mellitus: 3 latent, 4 type I and
      3 type II. Eight of the diabetic patients presented multiple and 5 generalized
      GA. They suffered significantly more often from chronic relapsing GA than
      nondiabetic patients.

PMID- 8993974
TI  - Livedo-like dermatitis (Nicolau's syndrome): a review of three cases.
AB  - We report 3 patients with typical features of livedo-like dermatitis. Emergency
      vasoactive therapy was administered to 2 of these patients, in whom the lesions
      healed completely. Although spontaneous resolution cannot be ruled out, we think
      that early recognition of this entity leading to rapid vasoactive treatment may
      limit the extent of thrombotic complications and the resulting tissue necrosis.

PMID- 8993975
TI  - Evaluation of MYC and chromosome 8 copy number in breast carcinoma by interphase
      cytogenetics.
AB  - We used fluorescence in situ hybridization (FISH) to determine MYC and chromosome
      8 copy number on whole nuclear imprint preparations of 24 breast carcinomas,
      seven benign breast samples, and two phyllodes tumors. None of the benign tissues
      and neither of the phyllodes tumors demonstrated an increased copy number for MYC
      or chromosome 8, which was defined as greater than two signals in > 10% of
      nuclei. In contrast, 22 of 24 carcinomas demonstrated an increased MYC copy
      number. The modal numbers of MYC copies/nucleus were 0-2 in seven cases (29%), 3
      5 in seven cases (29%), 6-9 in five cases (21%), and > 9 in five cases (21%). An
      increased chromosome 8 copy number was observed in 21 of 22 carcinomas with MYC
      gain, and the modal number of signals/nucleus was either identical to (n = 14;
      64%) or less than (n = 8; 36%) the number of MYC copies. The number of MYC copies
      correlated with cellular DNA content, as determined by using flow cytometry. In
      peridiploid tumors (DNA index 0.9-1.2; n = 7), the MYC copy numbers/nucleus were
      0-2 in five cases and 3-5 in two cases. In contrast, the modal MYC copy
      numbers/nucleus among the 11 hyperdiploid tumors (DNA index 1.3-1.9) were 0-2 in
      one case, 3-5 in four cases, 6-9 in five cases, and > 9 in one case. All three
      tetraploid/hypertetraploid carcinomas exhibited > 9 MYC copies/nucleus. We
      conclude that an increased MYC copy number, as detected by using interphase
      cytogenetics, is extremely frequent in human breast carcinomas. However, in most
      cases, MYC gene duplication is probably secondary to polysomy of chromosome 8
      and/or genomic endoreduplication (i.e., DNA aneuploidy).

PMID- 8993976
TI  - Characterization of MSH2 and MLH1 mutations in Italian families with hereditary
      nonpolyposis colorectal cancer.
AB  - Mismatch repair genes MSH2 and MLH1 are considered to be the two major genes that
      are responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Germline
      heterozygous inactivating mutations of MSH2 and MLH1 have been identified
      previously in a substantial fraction of individuals who are predisposed
      genetically to colorectal carcinoma (CRC) and other tumors of the HNPCC spectrum.
      With the aim of determining the relevance of these two genes in the Italian
      population, we submitted to mutational analysis a set of 17 HNPCC families, all
      of which fulfilled the "Amsterdam criteria." A combination of different
      techniques, including reverse transcription-polymerase chain reaction (RT-PCR) of
      long fragments and single-strand conformation polymorphism (SSCP) on cDNA and
      genomic DNA, allowed the identification of ten molecular variants, seven of which
      are predicted to inactivate mismatch repair function. The mutated predisposing
      gene was MSH2 in two families and MLH1 in five other families. All of the
      mutations were characterized by DNA sequencing and appeared to involve different
      molecular mechanisms, such as short in-frame and out-of-frame deletions, splicing
      errors, and nonsense mutations. This study also demonstrates that, in the Italian
      population, a considerable fraction of HNPCC families (at least 41%) is linked to
      MSH2 and MLH1 mutations.

PMID- 8993977
TI  - Genomic instability in sporadic colorectal cancer quantitated by inter-simple
      sequence repeat PCR analysis.
AB  - Genomic instability plays a major role in cancer by facilitating tumor
      progression and tumor heterogeneity. Inter-simple sequence repeat (inter-SSR) PCR
      has been developed to provide a rapid and reproducible technique for quantitation
      of the major type of genomic instability observed in sporadic tumors, namely,
      that manifesting itself as amplifications, deletions, translocations, and
      insertions. Evaluation of 59 sporadic colorectal cancers by inter-SSR PCR has
      demonstrated a wide range of instability, independent of tumor stage at
      diagnosis. Comparison of these data and the results of microsatellite PCR
      analysis reveals an association of high genomic instability with loss of
      heterozygosity but no association with the replication error phenomenon arising
      from defects in mismatch repair.

PMID- 8993978
TI  - Alu-polymerase chain reaction genomic fingerprinting technique identifies
      multiple genetic loci associated with pancreatic tumourigenesis.
AB  - DNA fingerprinting can be used to detect genetic rearrangements in cancer that
      may be associated with activation of oncogenes and inactivation of tumour
      suppressor genes. We have developed a fingerprinting strategy based on polymerase
      chain reaction (PCR) amplification of genomic DNA with primers specific for the
      Alu repeat sequences, which are highly abundant in the human genome. This has
      been applied to DNA from pancreatic cancer and paired normal samples to isolate
      and identify fragments of genomic DNA rearranged in the malignant cells. These
      fragments have been sequenced and used as probes to isolate hybridising clones
      from gridded bacteriophage P1, phage artificial chromosome, and cosmid libraries
      for fluorescent in situ hybridisation mapping and the identification of expressed
      sequences. Further characterisation has identified a putative novel gene (ART1)
      that is up-regulated specifically in pancreatic cancer as well as another
      sequence with similarity to genes involved in differentiation (POU domains). In
      conclusion, we suggest that Alu-PCR fingerprinting may be a useful technique for
      the identification of genes involved in tumourigenesis.

PMID- 8993979
TI  - Mutations in MLH1 are more frequent than in MSH2 in sporadic colorectal cancers
      with microsatellite instability.
AB  - The microsatellite instability that is a feature of tumors in patients with
      hereditary nonpolyposis colorectal cancer (HNPCC) is a consequence of defective
      DNA mismatch repair. Mutations in the DNA mismatch repair genes MSH2 and MLH1 may
      account for up to 90% of HNPCC kindreds. Microsatellite instability is also seen
      in 10-16% of sporadic colorectal cancers. A limited number of MSH2 and MLH1
      mutations have been described for sporadic colorectal cancers. In this study, we
      screened 12 primary sporadic colorectal cancers with microsatellite instability
      for mutations in MSH2 and MLH1 by using reverse transcription-polymerase chain
      reaction (RT-PCR) and single-strand-conformation-variant (SSCV) analysis. Eight
      mutations were identified in six tumors. One mutation in MLH1 was found to be
      present in the patient's germline DNA. Four tumors had somatic mutations in MLH1,
      and, in two of these tumors, two different mutations were identified. A single
      tumor had a somatic MSH2 mutation. Our observations suggest that MLH1 is mutated
      more frequently than MSH2 in sporadic colorectal cancers with microsatellite
      instability.

PMID- 8993980
TI  - High-resolution deletion mapping of chromosome arm 17p in childhood primitive
      neuroectodermal tumors reveals a common chromosomal disruption within the Smith
      Magenis region, an unstable region in chromosome band 17p11.2.
AB  - Loss of heterozygosity (LOH) on chromosome arm 17p is the most common genetic
      aberration in childhood primitive neuroectodermal tumors (PNETs). To determine
      the frequency and extent of 17p deletions, 29 loci on 17p were investigated in 24
      tumors by using restriction fragment length polymorphism (RFLP) and
      microsatellite analysis. LOH on 17p was found in 9 of 24 tumors. In all tumors
      with LOH, a continuous stretch from the telomere to chromosome band 17p11.2 was
      completely deleted, and no interstitial or terminal small-scale deletions were
      detected in the remaining 15 tumors. In four tumors with LOH on 17p, the
      chromosomal breakpoint was located between D17S953 and D17S805. To identify this
      deletion breakpoint on the cytogenetic map of chromosome 17 and to exclude
      uniparental disomy, we verified our data by using fluorescence in situ
      hybridization (FISH) analyses. By using two yeast artificial chromosome (YAC)
      clones that were positive for D17S689 and D17S953, the same breakpoint was
      confirmed in two specimens of cerebrospinal fluid (CSF) metastases by using FISH
      on interphase preparations. We demonstrate that, in most childhood PNETs with LOH
      on 17p, the breakpoint is close to, but not within, the centromere. It varies,
      and it occurs predominantly between the two markers D17S689 and D17S953, which is
      an unstable chromosomal region that is deleted or duplicated in the Smith-Magenis
      syndrome. Because LOH of 17p is associated with the formation of isochromosome
      17q in the majority of PNETs, this study provides entry points to determine the
      molecular nature of this phenomenon.

PMID- 8993981
TI  - Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by
      comparative genomic hybridization.
AB  - Comparative genomic hybridization (CGH) was used to evaluate and map genomic
      aberrations in 50 hepatocellular carcinomas (HCCs) from patients chronically
      infected with hepatitis B virus (HBV). CGH clearly detected nonrandom genomic
      imbalances. Losses were most prevalent on chromosome regions 4q (70%), 8p (65%),
      16q (54%), 17p (51%), 13q and 6q (37% each), and lp (30%). The most frequent
      gains occurred on 8q (60%), 1q (58%), and 6p and 17q (33% each). In a few cases,
      sequence amplifications were detected that were mapped to bands 11q12, 12p11,
      14q12, and 19q13.1. This study represents the first analysis of primary liver
      cancers by CGH, and it confirms the presence of previously known chromosomal
      aberrations in HCC and highlights new quantitative abnormalities and sequence
      amplifications. These findings should lead to the characterization of new loci
      involved in liver cancer pathogenesis.

PMID- 8993982
TI  - Complexity of 12q13-22 amplicon in liposarcoma: microsatellite repeat analysis.
AB  - The 12q13-22 amplicon from four liposacroma specimens evaluated by comparative
      genomic hybridization was studied analyzing 55 microsatellite markers by PCR. All
      four specimens were informative in at least 34 loci; an amplification or allelic
      imbalance was identified with four to 17 markers. The amplicons were
      discontinuous; there were non-amplified marker loci between the amplified marker
      loci. These findings indicate the presence of separate amplicons in the 12q13-22
      region. Evidence of the concomitant gain of one allele and loss of the other
      allele was found with several markers in one tumor and with one marker in two
      tumor specimens. Southern blotting showed amplification of CDK4 and MDM2 in all
      four specimens.

PMID- 8993983
TI  - Importance of calibration for diameter and area determination by intravascular
      ultrasound.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) permits quantitative assessment of
      the lumen diameter and area of coronary arteries. The experimental study was
      performed to evaluate the accuracy of diameter and area measurements. METHODS AND
      RESULTS: Lumen quantitation (lumen diameter D and cross-sectional area A) in
      lucite tubes (lumen diameter 2.5 to 5.7 mm, Plexiglas) was performed using a
      mechanical IVUS system (HP console, 3.5 F catheter, Boston Scientific, 30 MHz).
      The influence of fluid type (blood, water and saline solution), fluid temperature
      (20 degrees C/37 degrees C), catheter to catheter variation, gain setting and
      ultrasound frequency (12, 20 and 30 MHz) was determined. In blood at 20 degrees C
      there was a constant deviation of the measured diameter from the true luminal
      diameter of -0.29 +/- -0.04 mm (p < 0.06). In water and saline solution at 20
      degrees C the mean deviation from true diameter was -0.21 +/- -0.06 mm (p <
      0.06). At 37 degrees C, the deviation in blood was greater than at 20 degrees (
      0.34 +/- -0.02 mm) which is > 10% in a 3 mm tube (p < 0.06). Three of the ten
      catheters tested in water at 20 degrees C underestimated true diameter by more
      than -0.3 mm. The deviation from true diameter (5 mm tube) with varying gain
      settings was -0.14 mm to -0.23 mm compared to -0.19 mm at standard settings (p >
      0.288). At 12 MHz diameter measured was over-estimated. The error in absolute
      area estimation increased with increasing diameter tested in blood at 37 degrees
      C (-1.21 to -2.72 mm2), whereas the relative error ([Measured Area-True
      Area]/True Area x 100 [%]) was more striking at smaller diameters (up to -25% in
      the 2.5 mm tube). CONCLUSION: Luminal diameters and areas are underestimated by
      this particular IVUS system. When IVUS imaging and measurements are made during
      coronary interventions this error should be taken into account with regard to
      appropriate sizing of the device and the assessment of the postprocedure result.
      Because systematic errors might also occur in other IVUS system (not tested in
      this study), it is advisable to ensure that each system is validated prior to
      clinical use, especially when exact measurements are required.

PMID- 8993984
TI  - Factors influencing the intravascular ultrasound dimensions and areas measured
      using mechanical transducers.

PMID- 8993985
TI  - Reproducibility of left ventricular size, shape and mass with echocardiography,
      magnetic resonance imaging and radionuclide angiography in patients with anterior
      wall infarction. A plea for core laboratories.
AB  - After myocardial infarction, left ventricular volume and ejection fraction can be
      assessed by echocardiography, magnetic resonance imaging and radionuclide
      angiography to guide therapy and determine prognosis. Whether a measured
      parameter gives the same results irrespective of the method used and the observer
      who performs the analysis is only partly known. Intra-observer and inter-observer
      variability were determined for echo and magnetic resonance imaging. Left
      ventricular ejection fraction measured by these techniques was related to
      radionuclide angiograms performed in the same period. Intra-observer variability
      for both echo and MRI was low and in most instances below 5%. Inter-observer
      variability for the echo and MRI measurements were substantially higher than
      intra-observer variability. Comparison of the three imaging modalities revealed
      systematic differences. Therefore, in clinical studies, left ventricular volume
      and function parameters have to be measured with the same technique and by the
      same observer in qualified core laboratories.

PMID- 8993986
TI  - Quantification of mitral valve stenosis by three-dimensional transesophageal
      echocardiography.
AB  - The aim of this study was the evaluation of the diagnostic potentials of
      transesophageal 3D- echocardiography in the determination of mitral valve
      stenosis. 54 patients were investigated by transthoracic and multiplane
      transesophageal echocardiography. In 41 patients cardiac catheterization was
      performed. 3D- echocardiographic data acquisition was performed by automatic
      transducer rotation at 2 degree increments over a span of 180 degrees. The
      transesophageal probe was linked to an ultrasound unit and to a 3D- workstation
      capable of ECG- and respiration gated data acquisition, postprocessing and 2D/3D
      image reconstruction. The mitral valve was visualized in sequential cross
      sectional planes out of the 3D data set. The spatial position of the planes was
      indicated in a reference image. In the cross-sectional plane with the narrowest
      part of the leaflets the orifice area was measured by planimetry. For topographic
      information a 3D view down from the top of the left atrium was reconstructed.
      Measurements were compared to conventional transthoracic planimetry, to Doppler
      echocardiographic pressure half time and to invasive data. The mean difference to
      transthoracic planimetry, pressure half time and to invasive measurements were
      0.3 +/- 0.1 cm2, 0.2 +/- 0.1 cm2 and 0.1 +/- 0.1 cm2, respectively. Remarkable
      differences between the 3D- echocardiographic and the 2D- or Doppler-
      echocardiographic methods were observed in patients with severe calcification or
      aortic regurgitation. In 22% of the patients the 3D data set was not of
      diagnostic quality. New diagnostic information from a 3D view of the mitral valve
      could be obtained in 69% of the patients. Thus, although image quality is
      limited, 3D- echocardiography provides new topographic information in mitral
      valve stenosis. It allows the use of a new quantitative method, by which image
      plane positioning errors and flow-dependent calculation is avoided.

PMID- 8993988
TI  - Influence of pulse repetition frequency and high pass filter on color Doppler
      maps of converging flow in vitro.
AB  - Assessment of regurgitant flow by the flow convergence method is based on reading
      absolute velocities from color Doppler maps. Velocity overestimation by high pass
      filtering above 100 Hz has been reported. An extremely low filter, however, is
      impracticable in patients. A ratio of pulse repetition frequency (PRF)/filter of
      10/1 usually results in good quality color maps as judged visually. We studied in
      vitro the influence of RPF and filter on the absolute velocities within color
      maps of the flow convergence, keeping PRF/filter at 10/1. The color maps were
      also compared with computerized flow simulations. Flow across different orifice
      plates was scanned using two different setups for each flow condition: low
      velocity setup (PRF 600-2500 Hz, filter 50-300 Hz) and high (PRF 1500-6000 Hz,
      filter 200-600 Hz). From the color maps, velocity profile curves were read along
      the flow center line across the flow convergence. The high velocity setup
      provided artefact-free color maps at a distance d = 2-4 through 8-11 mm to the
      orifice, the low setup at d = 6-8 through 18 mm. Within the overlapping range (d
      = 6-8 through 8-11 mm), the resulting curves showed no significant differences in
      local velocity, with a slight trend towards higher velocities with the high
      velocity setup (2.2-2.9%). The simulations agreed well with color Doppler except
      for slightly lower values at d > 10-12 mm. Changes in PRF and filter have no
      significant influence on the absolute velocities displayed within color maps as
      long as PRF/filter is kept close to 10/1.

PMID- 8993987
TI  - Provocation of left ventricular outflow tract obstruction in patients with
      hypertrophic cardiomyopathy. Comparison of orthostasis testing and nitrate
      application.
AB  - Several provocation maneuvers are described in hypertrophic cardiomyopathy to
      Doppler echocardiographically distinguish the obstructive from the non
      obstructive type. No data are available about the value of orthostasis testing in
      comparison with nitrate application in this disease. In this study, 16
      consecutive patients with hypertrophic cardiomyopathy were examined. 11 patients
      with hypertrophic cardiomyopathy were classified as obstructive, 5 patients with
      hypertrophic cardiomyopathy as non obstructive. Normal left ventricular outflow
      tract velocities as detected by the Doppler method were defined as < 2.0 m/s.
      Doppler echocardiographic measurements were performed after 10 minutes in supine
      position, within 10 minutes after head-up tilt and again, within 10 minutes in
      supine position. If systolic blood pressure during this examination exceeded 100
      mm Hg 2.5 mg isosorbiddinitrate were sprayed sublingually. Measurements were done
      after 20 minutes in supine position and within 10 minutes after head-up tilt.
      Only in 7 of the 11 patients with hypertrophic obstructive cardiomyopathy maximal
      left ventricular outflow tract velocity in supine position measured > 2.0 m/s
      (2.2 +/- 0.8). During head-up tilt, all patients showed increased values (3.8 +/-
      1.2 m/s). No differences in maximal left ventricular outflow tract velocity
      between head-up tilt and nitrate application in supine position (3.5 +/- 1.4 m/s)
      were present. All patients with hypertrophic non obstructive cardiomyopathy
      showed maximal left ventricular outflow tract velocities < 2.0 m/s in every step
      of the examination. Consequently, orthostasis testing was able to identify all
      patients with hypertrophic obstructive cardiomyopathy and demonstrated a
      diagnostic value similar to nitrate application.

PMID- 8993990
TI  - Parameters that influence accuracy and precision of quantitative coronary
      arteriography.
AB  - The limited resolution of any imaging system causes edge blurring of objects
      acquired with X-ray. In digital angiography, this effect combined with noise
      gives rise to systematic and random errors in the determination of vessel
      dimensions. The influence of bandwidth limitation on the estimation of tube
      diameter is established by a theoretical approach: it leads to over and
      underestimations of catheter and vessel diameter dimensions. Therefore a
      correction is proposed that counterbalances the point spread function (PSF)
      offset. The residual inaccuracy and the variability of measurement of phantom
      tubes are analyzed and evaluated in controlled conditions. Some of the parameters
      which govern their extent are identified: field-of-view, catheter size,
      concentration of contrast agent.

PMID- 8993989
TI  - On-site digital quantitative coronary angiography: comparison with visual
      readings in interventional procedures. Implications for decision and quality
      control.
AB  - In order to review the morphological criterion for an interventional procedure,
      diameter stenosis (%DS) of 226 coronary lesions in 200 patients undergoing
      elective coronary angiography with an option for 'prima vista' angioplasty
      (pPTCA), was assessed on-site by both visual 'eye balling' (EB) and independent
      digital quantitative coronary angiography (DQCA) by means of an angiographic
      workstation. Compared to DQCA, EB overestimated the %DS between 50 and 80% and
      accounted for the majority of discrepancies with overestimation up to 45%.
      Concordant estimates of %DS by both methods were observed in only 10 of the total
      of 226 stenotic segments; in 20 of 226 cases, EB underestimated %DS up to 20%. EB
      revealed a %DS > or = 60% in 166 stenoses (73.4%), an estimate that led to
      subsequent pPTCA. However, only 119 (52.6%) of these lesions had a %DS > or = 60%
      as assessed objectively by DQCA. With regard to the criterion for PTCA 47 of 166
      performed pPTCA (28.3%) would not meet the indication criteria based on objective
      DQCA information. EB and DQCA (+/-5%DS) had concordant results and criteria for
      pPTCA only in 103 of 166 coronary lesions (62.1%). These results lead to the
      conclusion that, on-site and on-line DQCA by an independent cardiologist
      eliminates both under- and overestimation of stenoses as seen with EB. DQCA
      supports immediate decision-making and appears necessary for reliable evaluation
      of coronary morphology in an interventional catheterization laboratory setting
      and may eventually ensure intraprocedural quality control.

PMID- 8993991
TI  - The impact of vessel orientation in space on densitometric measurements of cross
      sectional areas of coronary arteries.
AB  - Under ideal conditions, densitometric measurement of a coronary arterial cross
      section in biplane angiographic images should result in nearly equal cross
      sectional areas for both planes. However, quite appreciable discrepancies have
      been found by some authors in patients. In this study, the role of inadequate
      spatial orientation of the vessel axes relatively to the x-rays was assessed by
      use of a 3D technique applied to 60 stenoses (45 pre PTCA and 15 post PTCA) in
      simultaneously acquired digital biplane coronary angiograms of 27 CAD patients.
      The 3D technique yields two radius values per projection directly in mm at any
      arterial cross section of interest. This was used to determine the areas Ar(in
      mm2) of the reference cross sections. As with catheter calibration, these cross
      sections were thus assumed to be more or less circular, but out-of-plane effects
      and errors due to a catheter diameter determination in pixels were avoided. The
      areas of the stenotic sections were then determined densitometrically (in mm2)
      from the two projections (1 and 2) according to As1 = ArDs1/Dr1, resp. As2 =
      ArDs2/Dr2, where Dr1, Dr2, Ds1 and Ds2 are the conventional densitometric areas
      of the reference and stenotic cross sections measured in planes 1 and 2. As
      expected, the areas As1 and As2 correlated only moderately: As2 = 0.92 As1 + 0.7
      mm2, r = 0.82, n = 60, SEE = 1.4 mm2. The 3D method also yielded the two spatial
      angles between the local vessel axis and the X-rays of both planes. These two
      angles were then used to correct each densitometric area for inadequate
      orientation. With the corrected densitometric areas As1c and As2c, the
      correlation improved to: As2c = 1.05 As1c + 0.03 mm2, r = 0.93, n = 60, SEE = 0.8
      mm2. Inadequate orientation of the cross sections in space thus appears to be an
      important factor of inaccuracy in densitometric measurements of stenotic cross
      sections in patients.

PMID- 8993992
TI  - Validation of coronary artery saphenous vein bypass graft diameter measurements
      using quantitative angiography.
AB  - The accepted value for reproducibility (true change) is two standard deviations
      (SD) of the differences between repeat measurements. It has been well established
      for coronary artery measurements using several different quantitative coronary
      angiography (QCA) systems, but it has not been well documented for saphenous vein
      grafts (SVG). The purpose of this study was to assess, using the Cardiovascular
      Measurement System (CMS), the measurement reproducibility of 24 vein grafts from
      24 patients who had symptom-directed control angiography. Three equal graft
      segments were studied separately. Focal narrowings expressed in percent stenosis
      varied from 5 to 80% (mean 20.8 +/- 15.9%). The average minimum lumen diameter
      (MLD) was 3.07 +/- 0.81 mm and the average interpolated reference diameter (Ref.
      D) was 3.87 +/- 0.58 mm. We assessed the reproducibility of measurements obtained
      from two separate imagings of the graft in the same view but at least 20 minutes
      apart, near the beginning and at the end of the angiographic procedure
      (simulating baseline and end-trial examinations). The SD for differences in
      measurements (variability) was 0.183 mm for the MLD, 0.193 mm for the Ref.D,
      0.184 mm for the mean diameter (Mean D) and 3.72% for the percent diameter
      stenosis (PDS). A reasonable true change cut-off for SVG measurements in our
      laboratory is > or = 0.4 mm for the minimum and mean lumen diameters, and > or =
      10% for the PDS, when QCA is obtained with the QCA-CMS analytical software
      package.

PMID- 8993994
TI  - Application of dimension estimation and surrogate data to the time evolution of
      EEG topographic variables.
AB  - Dimensional complexity (estimated correlation dimension) was measured for two
      topographic EEG time series: (a) the time evolution of global field power (GFP)
      and (b) the time evolution of sequential dissimilarity (SQD) for resting, eyes
      closed and eyes-open data. Eyes-closed GFP and eyes-closed/open SQD all had an
      element of nonlinearity in their dynamics as evidenced by increased dimensional
      complexity associated with the phase-angle randomization, Gaussian surrogate-data
      procedure. However, none of the three gave any evidence of being deterministic
      chaotic processes. Eyes-open GFP dimensional complexity could not be
      distinguished from a linear-stochastic process.

PMID- 8993993
TI  - Neuronal dysfunction in heart failure assessed by cardiac 123-iodine
      metaiodobenzylguanidine scintigraphy.
AB  - In patients with chronic heart failure, increased sympathetic activity and
      cardiac sympathetic neuronal dysfunction are present and have been related to
      unfavourable clinical outcome. Modification of these alterations with the
      objective to improve prognosis has become an important aim of pharmacological
      therapy for these patients. A noninvasive technique to assess sympathetic
      neuronal function at the cardiac level may be valuable in evaluating newly
      developed therapeutic strategies. 123-iodine metaiodobenzylguanidine can be used
      to visualize cardiac sympathetic nerve function and activity. Single photon
      emission computerized tomographic is preferred to planar scintigraphy since it
      does not depend on superposition of other anatomical structures and may allow
      assessment of regional cardiac 123-iodine metaiodobenzylguanidine uptake.
      Although the quantitation of cardiac uptake in these tomographic images has
      several limitations, the use of the left ventricular cavity as a reference,
      calibrated by the 123-iodine activity in a blood sample drawn at the time of
      acquisition, may have clinical applications, with respect to the evaluation of
      therapeutical intervention in patients with heart failure.

PMID- 8993995
TI  - Pre- and post-stimulus processes in affective task and event-related
      desynchronization (ERD): do they discriminate anxiety coping styles?
AB  - The present investigation was designed to study whether pre-stimulus (as measured
      by EEG power in the time interval before the stimulus presentation) and post
      stimulus (as measured by event-related desynchronization (ERD)) processes of
      alpha components in two frequency bands (8-10 and 10-12 Hz) and their scalp
      distribution discriminate among anxiety coping styles in an affective task. We
      investigated this question by using a sample of 30 college students who were
      split into three groups consisting of 10 low-anxious (LA) and 10 high-anxious
      (HA) subjects, and 10 repressors (RE). In the present study, positive and
      negative emotions were operationalized by winning and losing certain amounts of
      money in gambling situation while measuring ERD to positive and negative feedback
      stimuli. The main findings of the prestimulus data analyses suggest that the
      prestimulus level of alpha power is sensitive to the anxiety coping styles. In
      terms of ERD effects, HA individuals were marked by relatively larger left
      hemisphere activation compared to low-anxious subjects and repressors. Further,
      in contrast to LA and RE, the phenomena observed in our experiment of increased
      and extended ERD over time in HA in response to negative feedback stimulation
      implies that threatening information (loss of money) is more persistently
      activated in subjects with high anxiety. Although preliminary, the reported
      findings are of potential importance because they could lead to the development
      of a new psychophysiological measure of relevance to personality.

PMID- 8993996
TI  - The association between P300 and age from preadolescence to early adulthood.
AB  - The present study examined the latency and amplitude of P300 in a large sample of
      subjects between 11 and 21 years old. The P300 components of the visual event
      related potential showed consistent and significant age-related changes. Peak
      amplitude was found to diminish with increasing age, whereas peak latency
      decreased. Our data indicate that a linear relationship best explains the
      association between age and P300 amplitude and latency. The changes in P300
      amplitude and latency across the different ages are likely to reflect
      developmental changes in mental processing that are not due to a decrease in
      general cortical reactivity with increasing age or the result of subject
      noncompliance.

PMID- 8993997
TI  - Age-related changes in child and adolescent event-related potential component
      morphology, amplitude and latency to standard and target stimuli in an auditory
      oddball task.
AB  - Previous studies of auditory event-related potentials (ERPs) to an oddball task
      in children and adolescents focus on responses to target stimuli and provide
      little detail of age-related changes to standard stimuli. In this study, age
      related changes in behavioural responding and ERP component morphology, amplitude
      and latency to standard and target stimuli were examined. Auditory ERPs to an
      oddball task were recorded from the midline sites (Fz, Cz and Pz) of 50 subjects
      aged 8 to 17 years 11 months. Behavioural results indicate a decrease in reaction
      time and errors of commission with age. To standard tones, N2 amplitude and N1
      latency showed a linear decrease with age while an increase with age was found
      for P2 amplitude. For target tones, N1 and N2 amplitude and N1, N2 and P3 latency
      showed a linear decrease with age and P2 and P3 amplitude showed a linear
      increase with age. Age-related changes in the morphology of the ERP elicited by
      standard tones (especially the N2 and P2 components), as well as concurrent
      morphological changes in standard and target tones, are discussed.

PMID- 8993998
TI  - Self-generated happy and sad emotions in low and highly hypnotizable persons
      during waking and hypnosis: laterality and regional EEG activity differences.
AB  - EEG correlates of self-generated happy and sad emotions during counterbalanced
      conditions of waking and hypnosis were investigated in 16 low ("lows') and 15
      highly ("highs') hypnotizable men, as assessed by the Harvard Group Scale of
      Hypnotic Susceptibility and the Stanford Hypnotic Susceptibility Scale, Form C.
      Using log mean spectral magnitude, 11 frequency bands (3.5-42 Hz) were evaluated
      at frontal (F3, F4), central (C3, C4), and parietal (P3, P4) regions. As
      anticipated, only parietal hemispheric differences in low alpha activity (7.5
      9.45 Hz) differentiated between emotions, whereas mid and high alpha activity
      (9.5-13.45 Hz) did not. There was significantly less low alpha activity in right
      parietal (P4) in sad than happy emotions, supportive of prior research showing
      relatively greater right hemispheric involvement in negative than positive
      emotions. Yet, overall there was more low alpha activity in the left parietal
      (P3) region. During sadness only in waking, low beta (13.5-15.45 Hz) activity was
      greater in the right than left frontal region, greater in the left than right
      central region, and similar in both hemispheres in the parietal region. As
      anticipated, in comparison to lows, highs showed significantly greater
      hemispheric asymmetries (right greater than left) in the parietal region in high
      theta (5.5-7.45 Hz), high alpha (11.5-13.45 Hz), and beta activity between 16.5
      and 25 Hz-all frequency bands that are associated with sustained attentional
      processing. Results support prior research (for reviews, see Crawford, 1994a;
      Crawford and Gruzelier, 1992) that highs have greater sustained attentional
      abilities than do lows, which is reflected in different regional brain dynamics.
      Future EEG research needs to address narrower EEG frequency bands, as well as
      consider the moderating effects of hypnotic susceptibility level in observed
      hemispheric asymmetries.

PMID- 8993999
TI  - Comparison of dermatomal SEPs and operative findings in lumbar disc disease.
AB  - This report deals with an estimation of the diagnostic value of dermatomal
      somatosensory evoked potentials (SEPs), by correlating the neurophysiological
      data to clinical, neuroradiological and operative findings in lumbar disc
      protrusion. Our material consists of 12, surgically treated patients with lumbar
      disc protrusion in which diagnostic work up included history, neurological
      examination, routine lumbar spine films, computerised tomography and MRI of the
      lumbar spine, in addition to neurophysiological investigation, especially
      conduction velocity studies, and SEPs recorded by the standard methods, as well
      as after dermatomal stimulation. The retrospective analysis disclosed a
      correlation for the SEPs after dermatomal stimulation and surgical findings, in
      83% of our cases.

PMID- 8994000
TI  - Ulnar drift.

PMID- 8994001
TI  - 1996 presidential address. Bachelor of Science in Physical Therapy.

PMID- 8994002
TI  - Hand therapy trends in a changing South Africa.
AB  - A retrospective study prompted by the high incidence of traumatic hand injuries
      was undertaken to ascertain the nature of hand conditions treated at the Plastic
      and Reconstructive Surgery Unit of the Johannesburg Hospital in 1992, 1993, and
      1994. This three-year period marked a historically significant stage of political
      change that was accompanied by a high degree of violence and that occurred within
      a wider context of high unemployment, social upheaval, and stress associated with
      uncertainty about the future. Conditions treated with splinting, therapeutic
      activity, and home programs included complex traumas of the upper limb, tendon
      and nerve injuries, fractures, and burns. Assaults accounted for the largest
      number of injuries, and lesions to tendons predominated.

PMID- 8994003
TI  - Strength measurements of the lumbrical muscles.
AB  - This study was designed to measure the strength of the lumbrical muscles in the
      index and long fingers in patients with ulnar nerve paralysis. A hand-held
      dynamometer was used. The results show that in ulnar nerve damage the index and
      long fingers have a mean metacarpophalangeal (MCP) joint flexion strength of 0.8
      kg (range 0.3-1.5), compared with 6.4 kg (range 4.6-7.9) in the noninvolved hand.
      Thus, the damaged fingers have only about 12% of the strength of those of the
      noninvolved hand. In the hand with ulnar paralysis, the loss of intrinsic
      strength (dorsal and palmar interosseous muscles) is considerable (almost 90%).
      The contribution of the interosseous muscles in maintaining the intrinsic
      position is considerably greater than that of the lumbricals. Comparing the
      Medical Research Council (MRC) scale (0-5) with the dynamometry measurements
      shows that MRC grade 3 correlates with about 0.8 kg, while grade 5 correlates
      with about 6.5 kg of MCP joint flexion strength.

PMID- 8994004
TI  - An audit of flexor tendon injuries in zone II and its influence on management.
AB  - This paper reports the results of a one-year audit of flexor tendon injuries in
      zone II managed in a controlled mobilization program. It discusses the rationale
      for the use of this program and compares results with those of other units. On
      the basis of these results, the authors suggest that rehabilitation programs for
      patients with this type of injury should be tailored to individual needs and that
      trends in management should be carefully evaluated before implementation.

PMID- 8994005
TI  - Postoperative management of extensor tendon repairs in zones V, VI, and VII.
AB  - This paper describes the postoperative management plan for extensor tendon repair
      in zones V, VI, and VII as conceived by the Grenoble team. This plan includes
      immediate, postoperative systematic mobilization for all patients with surgical
      repairs in zones II through VIII. Postoperative mobilization in zones V and VI is
      performed under the protection of a Levame-type, dorsal steel leaf-blade spring.
      Depending on lesion location, proximal or distal to juncturae tendinum, Frere's
      three-finger rule applies. In zone VII, differential tendon gliding between the
      wrist and finger extensors and surrounding tissue is accomplished with a Tom
      splint, which gives individual extension assistance to each digit and the wrist
      while limiting flexion.

PMID- 8994006
TI  - Recovery of sensory and motor function after nerve repair. A rationale for
      evaluation.
AB  - In order to identify an effective test for evaluating the results of nerve
      repair, 25 patients, age 10-53 years (mean 27 years), were evaluated two to five
      years after median or ulnar nerve repair at the distal forearm level. The initial
      assumption was that evaluation after nerve repair should reflect four aspects of
      recovery: reinnervation, tactile gnosis, integrated sensory and motor functions,
      and pain or discomfort. The evaluation included a number of assessment methods
      addressing these aspects. Attention was paid to the usefulness of the tests with
      reference to their relevance for assessing hand functions. Clinical utility and
      possibilities for standardization and quantification of the results were
      considered important. Statistical analysis showed no correlations between the
      results obtained in clinical tests for reinnervation and the results from
      neurophysiologic examination. Grip strength and cold intolerance together
      accounted for a significant 51% of the variance in activities of daily living
      (ADL) capacity. Tactile gnosis correlated weakly with ADL capacity and strongly
      with age. Based on these findings, the following design for evaluating the result
      after median and ulnar nerve repair is suggested. To assess reinnervation: Semmes
      Weinstein monofilaments and manual muscle-testing; to assess tactile gnosis:
      classic 2PD and a test with the features of the used shape identification test;
      to assess integrated functions: selected parts of Sollerman's grip test and grip
      strength test with Jamar dynamometer; to quantify pain and discomfort: a four
      ranked scale for grading perceived problems from cold intolerance and
      hypersensitivity.

PMID- 8994007
TI  - Persistent mechanical allodynia following injury of the hand. Treatment through
      mobilization of the nervous system.
AB  - Mechanical allodynia (MA) following hand injury is a well-documented clinical
      problem. The purpose of this pilot study was to examine the relationship between
      hand MA and the upper limb tension test (ULTT). The ULTT mechanically stresses
      the neural structures from the C5/6/7 neural foramina to the median nerve
      distally. This study examined 29 subjects with unilateral hand MA before and
      after a 2-week neural self-mobilization programme. There was a significant
      difference between the subjects' affected and unaffected sides when tested using
      the ULTT, both in reproduction of symptoms and in reduced range of motion of the
      ULTT. Following the self-mobilization program, there was an improvement in the
      range of the ULTT, and subjects reported a reduction in their symptoms. Complete
      recovery was not obtained in all cases. The results of this study suggest that
      the ULTT is a useful tool both in assessment and treatment of subjects with hand
      MA.

PMID- 8994008
TI  - Management of pain in brachial plexus lesions.
AB  - Pain in avulsion lesions of the brachial plexus represents the most significant
      impediment to rehabilitation. The mechanism by which pain is felt is not widely
      understood. This paper demonstrates, how, with careful management, use of TENS
      can play a vital role in relief of pain and ultimate rehabilitation.

PMID- 8994009
TI  - Complications following surgical treatment for Dupuytren's contracture.
AB  - Dupuytren's disease is a proliferative fibroplasia that can lead to a significant
      contracture of the metacarpophalangeal (MCP) and interphalangeal (IP) joints,
      causing a functional disability. Surgical excision of the Dupuytren's tissue and
      release of the contracted joints may be necessary to restore function. Most
      patients require hand therapy postoperatively. Postoperative complications have
      been reported at 17%. These include excessive inflammation, hematoma, ischemic
      skin necrosis, infection, granuloma formation, transient paresthesia, scar
      contracture, persistent proximal interphalangeal (PIP) flexion contracture,
      distal interphalangeal (DIP) hyperextension deformity, joint stiffness, poor
      flexion and grip strength, pain, and reflex sympathetic dystrophy (RSD). The hand
      therapist plays a vital role in the early detection and treatment of many of
      these complications.

PMID- 8994011
TI  - The cooling effects of electroacupuncture on the skin temperature of the hand.
AB  - Electroacupuncture (EA) has been reported to induce changes in skin temperature;
      however, it is not clear whether high- and low-frequency EA produce similar
      effects. Therefore, the purpose of this study was to investigate the effects of
      EA on the skin temperature of the hand and finger in normal subjects. Twenty-one
      subjects received high-frequency EA (100 Hz) and low-frequency EA (4 Hz) at the
      Large Intestine 4 and Small Intestine 3 acupuncture points, as well as a no
      treatment control condition. The results showed that the skin temperature
      following high- and low-frequency EA produced significant cooling effects at both
      sites as compared with the no-treatment control condition during the stimulation
      period (p < 0.05). These data show that EA produces significant changes in skin
      temperature that may be of benefit in pathologic conditions that are accompanied
      by an increase in local circulation.

PMID- 8994010
TI  - Development and evaluation of a precision forearm and hand volumeter and
      measuring cylinder.
AB  - Water displacement methods are commonly used to measure upper limb swelling. The
      purpose of this study was to improve upon currently used volumetric equipment and
      methods by developing a volumetric method that would be reliable, accurate, and
      sensitive to changes in forearm and hand volume of less than 1%. The first two
      phases involved measuring a sample of inert objects (bottles), and the next two
      phases involved measuring a sample of forearms and hands across a range of water
      temperatures. Data confirmed that the volumetric method could be used reliably
      and accurately to measure bottle volumes and was able to detect a change of 10
      mls (< 1%). The method also reliably measured forearm and hand volumes using the
      same anatomic landmark to reference depth of immersion in all subjects. Water
      temperatures across the range of 20 to 32 degrees Celsius were not found to
      affect the volume of segments measured.

PMID- 8994012
TI  - What makes treatment for reflex sympathetic dystrophy successful?
AB  - Therapists throughout the world find it challenging to treat and rehabilitate
      patients with reflex sympathetic dystrophy. An insufficient understanding of the
      disease process often hinders the diagnosis, causing the patient unnecessary pain
      and distress. This paper presents effective diagnostic and treatment methods that
      emphasize patient trust as well as relaxation and range-of-motion exercises. The
      paper describes the cases of 120 women, aged 35 to 75 years, and 30 men, aged 30
      to 60 years. The condition was diagnosed in these patients three months after the
      onset of primary symptoms and was successfully treated.

PMID- 8994014
TI  - Splinting in the management of proximal interphalangeal joint flexion
      contracture.
AB  - Proximal interphalangeal (PIP) flexion contracture is a common complication
      following hand injuries and conditions. This study investigated the treatment
      outcome of 20 subjects with PIP flexion contracture who followed a dynamic
      splinting program using either a Capener or low-profile outrigger. The splint
      applied a 250-g force to the distal end of the middle phalanx. Each patient was
      instructed to wear the splint for 8 to 12 hours per 24 hours for 8 weeks followed
      by a 2- to 3-week weaning period. Passive extension was evaluated objectively
      using torque range-of-motion measurement. The average pretreatment flexion
      contracture was 39 degrees. Final extension deficit averaged 21 degrees, an
      improvement of 18 degrees. There was no statistically significant effect on final
      results based on joint stiffness (as expressed by the slopes of the torque angle
      curves). Total end-range time (TERT) averaged 10 hours per 24 hours, for an
      average period of 4.3 months. Statistical analysis showed that splinting time was
      the only statistically significant factor affecting outcome. The correlation
      coefficients showed that the longer the contracture was present, the stiffer the
      joint and the less the contracture resolved. Dynamic splinting was an effective
      form of treatment for PIP flexion contracture.

PMID- 8994013
TI  - Evaluation of the effectiveness of a metacarpophalangeal ulnar deviation
      orthosis.
AB  - Rheumatoid arthritis (RA) causes structural damage that precipitates joint
      deformity, including metacarpophalangeal (MCP) joint ulnar drift (UD). Orthoses
      have been designed in order to maintain hand function by improving joint
      alignment, restoring biomechanical balance and reducing stress on supporting
      diseased tissues. This study investigated the impact an MCP UD (MUD) splint had
      on: pain, hand function, grip strength, and passive correction of UD when worn
      for function by RA patients. Twenty seven hands (26 subjects) were evaluated and
      performances compared with and without the splint. Results showed anatomic
      alignment improved significantly in all except the index finger. The mean
      difference for all fingers combined was 10 degrees. Observable correction of
      subluxation was identified from x-ray film and noted in 14.8% of index fingers,
      18.5% of middle fingers, 33.3% of ring fingers, and 48.1% of little fingers.
      Three point pinch showed a statistically significant change, the mean difference
      being an improvement of 15% while wearing the splint. There was no significant
      change in hand function score, pain score, gross grip strength, and lateral
      pinch. Subjects' perceptions of the MUD splint gained from a questionnaire showed
      a high acceptance: 79.2% reporting minimal interference in ADL, 95.8% satisfied
      with cosmesis, 87.5% satisfied with comfort, and 95.8% reported continued use of
      the orthosis.

PMID- 8994015
TI  - Neoprene wrist brace for correction of radial club hand in children.
AB  - Thermoplastic wrist orthoses have been used for some time for serial correction
      before surgery for radial dysplasia to realign the hand on the forearm bone.
      However, problems have been experienced with pressure areas, especially at the
      distal and proximal radial edges. Inserting padding with such a small orthosis
      (if made for a baby) distorts the fit. A neoprene brace has been developed that
      can be applied to an infant as young as 3 weeks old. Thermoplastic ulnar and
      radial reinforcers are used to maintain the correction. The method of
      construction and positioning are described. The reinforcers can be serially
      adjusted to achieve a neutral position at the wrist. In babies, passive
      correction may be easier to obtain, but in older children with soft-tissue
      shortening, acceptable realignment can be achieved serially and maintained until
      surgery is appropriate. Using neoprene avoids serious pressure problems. Neoprene
      is durable, washable, and accepted by this client group and their parents. It has
      been demonstrated that correcting the alignment of the hand improves hand
      function, especially in bilateral activities, and allows the child to swim and
      play in water while wearing it, thus enhancing the quality of life.

PMID- 8994016
TI  - The use of synthetic plaster casting tape for hand and wrist splints.
AB  - In a prospective study, 40 patients were fitted with synthetic plaster splints to
      assess the use of such material for hand and/or wrist splints. Factors assessed
      in both splint fabrication and use included molding properties, elastic traction
      fixation, weight, ventilation, durability, patient comfort, effectiveness,
      practicability, time, and cost. The patients were divided into three groups
      according to basic pathology: tendon/nerve injuries; bone and joint disorders;
      and rheumatoid disease deformities. Recovery of 50-100% of active range of motion
      was considered a good result. Good results were obtained in 37 patients (92.5%),
      whereas in the remaining three patients (7.5%) the results were poor. It is
      suggested that synthetic plaster is a suitable material for the fabrication of
      splints in hand rehabilitation.

PMID- 8994017
TI  - Functional assessment of repetitive strain injuries: two case studies.
AB  - More patients with repetitive strain injuries (RSIs) are being seen in
      occupational therapy clinics in Hong Kong. To reduce the incidence of work
      related RSIs, it is necessary to identify problem jobs and/or specific tasks that
      are associated with an increased risk of these disorders. Physical assessment,
      videotaping, ergonomic evaluations, and analyses of workstation designs are used
      for this purpose. In Hong Kong, however, these methods cannot be implemented at
      the jobsite without the approval of the employer. This restriction constitutes a
      major problem in planning the rehabilitation of workers who have RSIs. A self
      assessment method using the Work Evaluation Systems Technology (WEST) Tool Sort
      and the LLUMC Activity Sort was adopted as part of the evaluation of clients with
      RSIs. The questionnaires were translated into Chinese and reviewed and revised
      for content validity by ten occupational therapists. Two case studies are
      presented to illustrate the occupational therapy intervention program based on
      this self-report instrument. The questionnaires were found to be efficient and
      useful in assessing the client's abilities at work and in explaining to the
      client the relationship of his or her working conditions to the RSIs.

PMID- 8994018
TI  - Rehabilitation of patient with brachial plexus lesion and break in axillary
      artery. Case study.
AB  - This paper describes the physiotherapy and occupational therapy used in treating
      a 74-year-old woman with a left brachial plexus lesion, a break in the axillary
      artery, dislocation of the acromioclavicular joint, a broken scapula and
      clavicula, serial left rib fractures, and lacerations on the upper and lower arm.
      After testing the patient, the following goals were set: reduce pain, soften scar
      tissue, and improve joint motion, muscle strength, and functionality of the hand.
      A 12-month outpatient program was used. Various analgesics were used to reduce
      pain, and a special aid was made to unweight the shoulder and elbow joints.
      Physiotherapy included kinesiotherapy, audiovisual biofeedback, electrical
      stimulation, friction massage, and lymph drainage. Occupational therapy included
      active functional exercises and re-education. As a result of this program, the
      patient no longer had pain, passive range of motion was close to normal, active
      motion where present was improved, swelling was reduced, and the hand became
      functional again. Complex physiotherapy, occupational therapy, and the patient's
      motivation resulted in the rehabilitation of severe trauma of the hand.

PMID- 8994019
TI  - Fracture bracing for proximal phalanx fractures.

PMID- 8994020
TI  - A device for tension adjustment on dynamic splints.

PMID- 8994021
TI  - Development of extensor lag in treating boutonniere deformity.

PMID- 8994022
TI  - Information retrieval in digital libraries: bringing search to the net.
AB  - A digital library enables users to interact effectively with information
      distributed across a network. These network information systems support search
      and display of items from organized collections. In the historical evolution of
      digital libraries, the mechanisms for retrieval of scientific literature have
      been particularly important. Grand visions in 1960 led first to the development
      of text search, from bibliographic databases to full-text retrieval. Next,
      research prototypes catalyzed the rise of document search, from multimedia
      browsing across local-area networks to distributed search on the Internet. By
      2010, the visions will be realized, with concept search enabling semantic
      retrieval across large collections.

PMID- 8994023
TI  - Mathematical and computational challenges in population biology and ecosystems
      science.
AB  - Mathematical and computational approaches provide powerful tools in the study of
      problems in population biology and ecosystems science. The subject has a rich
      history intertwined with the development of statistics and dynamical systems
      theory, but recent analytical advances, coupled with the enhanced potential of
      high-speed computation, have opened up new vistas and presented new challenges.
      Key challenges involve ways to deal with the collective dynamics of heterogeneous
      ensembles of individuals, and to scale from small spatial regions to large ones.
      The central issues-understanding how detail at one scale makes its signature felt
      at other scales, and how to relate phenomena across scales-cut across scientific
      disciplines and go to the heart of algorithmic development of approaches to high
      speed computation. Examples are given from ecology, genetics, epidemiology, and
      immunology.

PMID- 8994024
TI  - An information-intensive approach to the molecular pharmacology of cancer.
AB  - Since 1990, the National Cancer Institute (NCI) has screened more than 60,000
      compounds against a panel of 60 human cancer cell lines. The 50-percent growth
      inhibitory concentration (GI50) for any single cell line is simply an index of
      cytotoxicity or cytostasis, but the patterns of 60 such GI50 values encode
      unexpectedly rich, detailed information on mechanisms of drug action and drug
      resistance. Each compound's pattern is like a fingerprint, essentially unique
      among the many billions of distinguishable possibilities. These activity patterns
      are being used in conjunction with molecular structural features of the tested
      agents to explore the NCI's database of more than 460,000 compounds, and they are
      providing insight into potential target molecules and modulators of activity in
      the 60 cell lines. For example, the information is being used to search for
      candidate anticancer drugs that are not dependent on intact p53 suppressor gene
      function for their activity. It remains to be seen how effective this information
      intensive strategy will be at generating new clinically active agents.

PMID- 8994025
TI  - Bulk Spin-Resonance Quantum Computation
AB  - Quantum computation remains an enormously appealing but elusive goal. It is
      appealing because of its potential to perform superfast algorithms, such as
      finding prime factors in polynomial time, but also elusive because of the
      difficulty of simultaneously manipulating quantum degrees of freedom while
      preventing environmentally induced decoherence. A new approach to quantum
      computing is introduced based on the use of multiple-pulse resonance techniques
      to manipulate the small deviation from equilibrium of the density matrix of a
      macroscopic ensemble so that it appears to be the density matrix of a much lower
      dimensional pure state. A complete prescription for quantum computing is given
      for such a system.

PMID- 8994026
TI  - Alterations in synaptic strength preceding axon withdrawal.
AB  - Permanent removal of axonal input to postsynaptic cells helps shape the pattern
      of neuronal connections in response to experience, but the process is poorly
      understood. Intracellular recording from newborn and adult mouse muscle fibers
      temporarily innervated by two axons showed an increasing disparity in the
      synaptic strengths of the two inputs before one was eliminated. The connection
      that survived gained strength by increasing the amount of neurotransmitter
      released (quantal content), whereas the input that was subsequently removed
      became progressively weaker, because of a reduction in quantal content and a
      reduction in quantal efficacy associated with reduced postsynaptic receptor
      density. Once the synaptic strengths of two inputs began to diverge, complete
      axonal withdrawal of the weaker input occurred within 1 to 2 days. These
      experiments provide a link between experience-driven changes in synaptic strength
      and long-term changes in connectivity in the mammalian nervous system.

PMID- 8994028
TI  - Reconstruction of Current Flow and Imaging of Current-Limiting Defects in
      Polycrystalline Superconducting Films
AB  - Magneto-optical imaging was used to visualize the inhomogeneous penetration of
      magnetic flux into polycrystalline TlBa2Ca2Cu3Ox films with high critical current
      densities, to reconstruct the local two-dimensional supercurrent flow patterns
      and to correlate inhomogeneities in this flow with the local crystallographic
      misorientation. The films have almost perfect c-axis alignment and considerable
      local a- and b-axis texture because the grains tend to form colonies with only
      slightly misaligned a and b axes. Current flows freely over these low-angle grain
      boundaries but is strongly reduced at intermittent colony boundaries of high
      misorientation. The local (<10-micrometer scale) critical current density Jc
      varies widely, being up to 10 times as great as the transport Jc (scale of
      approximately 1 millimeter), which itself varies by a factor of about 5 in
      different sections of the film. The combined experiments show that the magnitude
      of the transport Jc is largely determined by a few high-angle boundaries.

PMID- 8994027
TI  - Stereoselective bimolecular phenoxy radical coupling by an auxiliary (dirigent)
      protein without an active center.
AB  - The regio- and stereospecificity of bimolecular phenoxy radical coupling
      reactions, of especial importance in lignin and lignan biosynthesis, are clearly
      controlled in some manner in vivo; yet in vitro coupling by oxidases, such as
      laccases, only produce racemic products. In other words, laccases, peroxidases,
      and comparable oxidases are unable to control regio- or stereospecificity by
      themselves and thus some other agent must exist. A 78-kilodalton protein has been
      isolated that, in the presence of an oxidase or one electron oxidant, effects
      stereoselective bimolecular phenoxy radical coupling in vitro. Itself lacking a
      catalytically active (oxidative) center, its mechanism of action is presumed to
      involve capture of E-coniferyl alcohol-derived free-radical intermediates, with
      consequent stereoselective coupling to give (+)-pinoresinol.

PMID- 8994029
TI  - Hillslope Evolution by Bedrock Landslides
AB  - Bedrock landsliding is a dominant geomorphic process in a number of high-relief
      landscapes, yet is neglected in landscape evolution models. A physical model of
      sliding in beans is presented, in which incremental lowering of one wall
      simulates baselevel fall and generates slides. Frequent small slides produce
      irregular hillslopes, on which steep toes and head scarps persist until being
      cleared by infrequent large slides. These steep segments are observed on
      hillslopes in high-relief landscapes and have been interpreted as evidence for
      increases in tectonic or climatic process rates. In certain cases, they may
      instead reflect normal hillslope evolution by landsliding.

PMID- 8994030
TI  - An Explanation for Earth's Long-Term Rotational Stability
AB  - Paleomagnetic data show less than approximately 1000 kilometers of motion between
      the paleomagnetic and hotspot reference frames-that is, true polar wander-during
      the past 100 million years, which implies that Earth's rotation axis has been
      very stable. This long-term rotational stability can be explained by the slow
      rate of change in the large-scale pattern of plate tectonic motions during
      Cenozoic and late Mesozoic time, provided that subducted lithosphere is a major
      component of the mantle density heterogeneity generated by convection. Therefore,
      it is unnecessary to invoke other mechanisms, such as sluggish readjustment of
      the rotational bulge, to explain the observed low rate of true polar wander.

PMID- 8994031
TI  - Depletion of the Outer Asteroid Belt
AB  - During the early history of the solar system, it is likely that the outer planets
      changed their distance from the sun, and hence, their influence on the asteroid
      belt evolved with time. The gravitational influence of Jupiter and Saturn on the
      orbital evolution of asteroids in the outer asteroid belt was calculated. The
      results show that the sweeping of mean motion resonances associated with
      planetary migration efficiently destabilizes orbits in the outer asteroid belt on
      a time scale of 10 million years. This mechanism provides an explanation for the
      observed depletion of asteroids in that region.

PMID- 8994032
TI  - Kinetic measurement of the step size of DNA unwinding by Escherichia coli UvrD
      helicase.
AB  - The kinetic mechanism by which the DNA repair helicase UvrD of Escherichia coli
      unwinds duplex DNA was examined with the use of a series of oligodeoxynucleotides
      with duplex regions ranging from 10 to 40 base pairs. Single-turnover unwinding
      experiments showed distinct lag phases that increased with duplex length because
      partially unwound DNA intermediate states are highly populated during unwinding.
      Analysis of these kinetics indicates that UvrD unwinds duplex DNA in discrete
      steps, with an average "step size" of 4 to 5 base pairs (approximately one-half
      turn of the DNA helix). This suggests an unwinding mechanism in which alternating
      subunits of the dimeric helicase interact directly with duplex DNA.

PMID- 8994033
TI  - Receptor and betagamma binding sites in the alpha subunit of the retinal G
      protein transducin.
AB  - Transmembrane receptors for hormones, neurotransmitters, light, and odorants
      mediate their cellular effects by activating heterotrimeric guanine nucleotide
      binding proteins (G proteins). Crystal structures have revealed contact surfaces
      between G protein subunits, but not the surfaces or molecular mechanism through
      which Galphabetagamma responds to activation by transmembrane receptors. Such a
      surface was identified from the results of testing 100 mutant alpha subunits of
      the retinal G protein transducin for their ability to interact with rhodopsin.
      Sites at which alanine substitutions impaired this interaction mapped to two
      distinct Galpha surfaces: a betagamma-binding surface and a putative receptor
      interacting surface. On the basis of these results a mechanism for receptor
      catalyzed exchange of guanosine diphosphate for guanosine triphosphate is
      proposed.

PMID- 8994034
TI  - Consumer Versus Resource Control in Freshwater Pelagic Food Webs
AB  - Models predict that food-web structure is regulated by both consumers and
      resources, and the strength of this control is dependent on trophic position and
      food-web length. To test these hypotheses, a meta-analysis was conducted of 11
      fish (consumer)-by-nutrient (resource) factorial plankton community experiments.
      As predicted, zooplankton biomass was under strong consumer control but was
      weakly stimulated by nutrient additions; phytoplankton biomass was under strong
      resource control with moderate control by fish. However, the phytoplankton and
      zooplankton responses to nutrient additions did not follow theoretical
      predictions based on the number of trophic levels in the food web.

PMID- 8994035
TI  - Functional specificity among Hsp70 molecular chaperones.
AB  - Molecular chaperones of the 70-kilodalton heat shock protein (Hsp70) class bind
      to partially unfolded polypeptide substrates and participate in a wide variety of
      cellular processes. Differences in peptide-binding specificity among Hsp70s have
      led to the hypothesis that peptide binding determines specific Hsp70 functions.
      Protein domains were identified that were required for two separate functions of
      a yeast Hsp70 family. The peptide-binding domain was not required for either of
      these specific Hsp70 functions, which suggests that peptide-binding specificity
      plays little or no role in determining Hsp70 functions in vivo.

PMID- 8994036
TI  - Chaotic Dynamics in an Insect Population
AB  - A nonlinear demographic model was used to predict the population dynamics of the
      flour beetle Tribolium under laboratory conditions and to establish the
      experimental protocol that would reveal chaotic behavior. With the adult
      mortality rate experimentally set high, the dynamics of animal abundance changed
      from equilibrium to quasiperiodic cycles to chaos as adult-stage recruitment
      rates were experimentally manipulated. These transitions in dynamics corresponded
      to those predicted by the mathematical model. Phase-space graphs of the data
      together with the deterministic model attractors provide convincing evidence of
      transitions to chaos.

PMID- 8994037
TI  - A mouse model with features of familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is a common inherited lipid disorder,
      affecting 1 to 2 percent of the population in Westernized societies. Individuals
      with FCHL have large quantities of very low density lipoprotein (VLDL) and low
      density lipoprotein (LDL) and develop premature coronary heart disease. A mouse
      model displaying some of the features of FCHL was created by crossing mice
      carrying the human apolipoprotein C-III (APOC3) transgene with mice deficient in
      the LDL receptor. A synergistic interaction between the apolipoprotein C-III and
      the LDL receptor defects produced large quantities of VLDL and LDL and enhanced
      the development of atherosclerosis. This mouse model may provide clues to the
      origin of human FCHL.

PMID- 8994039
TI  - Uniting Two General Patterns in the Distribution of Species
AB  - Two patterns in the distribution of species have become firmly but independently
      established in ecology: the species-area curve, which describes how rapidly the
      number of species increases with area, and the positive relation between species'
      geographical distribution and average local abundance. There is no generally
      agreed explanation of either pattern, but for both the two main hypotheses are
      essentially the same: divergence of species along the ecological specialist
      generalist continuum and colonization- extinction dynamics. A model is described
      that merges the two mechanisms, predicts both patterns, and thereby shows how the
      two general, but formerly disconnected, patterns are interrelated.

PMID- 8994038
TI  - Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3
      kinase gamma.
AB  - The tyrosine kinase class of receptors induces mitogen-activated protein kinase
      (MAPK) activation through the sequential interaction of the signaling proteins
      Grb2, Sos, Ras, Raf, and MEK. Receptors coupled to heterotrimeric guanine
      triphosphate-binding protein (G protein) stimulate MAPK through Gbetagamma
      subunits, but the subsequent intervening molecules are still poorly defined.
      Overexpression of phosphoinositide 3-kinase gamma (PI3Kgamma) in COS-7 cells
      activated MAPK in a Gbetagamma-dependent fashion, and expression of a
      catalytically inactive mutant of PI3Kgamma abolished the stimulation of MAPK by
      Gbetagamma or in response to stimulation of muscarinic (m2) G protein-coupled
      receptors. Signaling from PI3Kgamma to MAPK appears to require a tyrosine kinase,
      Shc, Grb2, Sos, Ras, and Raf. These findings indicate that PI3Kgamma mediates
      Gbetagamma-dependent regulation of the MAPK signaling pathway.

PMID- 8994040
TI  - Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP
      kinases.
AB  - The proto-oncogene-encoded transcription factor c-Jun activates genes in response
      to a number of inducers that act through mitogen-activated protein kinase (MAPK)
      signal transduction pathways. The activation of c-Jun after phosphorylation by
      MAPK is accompanied by a reduction in c-Jun ubiquitination and consequent
      stabilization of the protein. These results illustrate the relevance of regulated
      protein degradation in the signal-dependent control of gene expression.

PMID- 8994041
TI  - Transmission of the BSE agent to mice in the absence of detectable abnormal prion
      protein.
AB  - The agent responsible for transmissible spongiform encephalopathies (TSEs) is
      thought to be a malfolded, protease-resistant version (PrPres) of the normal
      cellular prion protein (PrP). The interspecies transmission of bovine spongiform
      encephalopathy (BSE) to mice was studied. Although all of the mice injected with
      homogenate from BSE-infected cattle brain exhibited neurological symptoms and
      neuronal death, more than 55 percent had no detectable PrPres. During serial
      passage, PrPres appeared after the agent became adapted to the new host. Thus,
      PrPres may be involved in species adaptation, but a further unidentified agent
      may actually transmit BSE.

PMID- 8994042
TI  - The Drosophila erg K+ channel polypeptide is encoded by the seizure locus.
AB  - The eag family of K+ channels contains three known subtypes: eag, elk, and erg.
      Genes representing the first two subtypes have been identified in flies and
      mammals, whereas the third subtype has been defined only by the human HERG gene,
      which encodes an inwardly rectifying channel that is mutated in some cardiac
      arrhythmias. To establish the predicted existence of a Drosophila gene in the erg
      subfamily and to learn more about the structure and biological function of
      channels within this subfamily, we undertook a search for the Drosophila
      counterpart of HERG. Here we report the isolation and characterization of the
      Drosophila erg gene. We show that it corresponds with the previously identified
      seizure (sei) locus, mutations of which cause a temperature-sensitive paralytic
      phenotype associated with hyperactivity in the flight motor pathway. These
      results yield new insights into the structure and evolution of the eag family of
      channels, provide a molecular explanation for the sei mutant phenotype, and
      demonstrate the important physiological roles of erg-type channels from
      invertebrates to mammals.

PMID- 8994043
TI  - The seizure locus encodes the Drosophila homolog of the HERG potassium channel.
AB  - Mutations in the seizure (sei) locus cause temperature-induced hyperactivity,
      followed by paralysis. Gene cloning studies have established that the seizure
      gene product is the Drosophila homolog of HERG, a member of the eag family of K+
      channels implicated in one form of hereditary long QT syndrome in humans. A
      series of five null alleles with premature stop codons are all recessive, but
      viable. A missense mutation in the sei gene, which changes the charge at a
      conserved glutamate residue near the outer mouth of the pore, has a semidominant
      phenotype, suggesting that the mutant seizure protein acts as a poison in a
      multimeric complex. Transformation rescue of a null allele with a cDNA under the
      control of an inducible promoter demonstrates that induced expression of seizure
      potassium channels in adults rescues the paralytic phenotype. This rescue decays
      with a t1/2 of approximately 1-1.5 d after gene induction is discontinued,
      providing the first estimate of ion channel stability in an intact, multicellular
      animal.

PMID- 8994044
TI  - Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of
      sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient,
      mice.
AB  - TrkA high-affinity receptors are essential for the normal development of
      sympathetic paravertebral neurons and subpopulations of sensory neurons.
      Paravertebral sympathetic neurons and chromaffin cells of the adrenal medulla
      share an ontogenetic origin, responsiveness to NGF, and expression of TrkA. Which
      aspects of development of the adrenal medulla might be regulated via TrkA are
      unknown. In the present study we demonstrate that mice deficient for TrkA, but
      not the neurotrophin receptor TrkB, show an early postnatal progressive reduction
      of acetylcholinesterase (AChE) enzymatic activity in the adrenal medulla and in
      preganglionic sympathetic neurons within the thoracic spinal cord, which are also
      significantly reduced in number. Quantitative determinations of specific AChE
      activity revealed a massive decrease (-62%) in the adrenal gland and a lesser,
      but still pronounced, reduction in the thoracic spinal cord (-40%). Other markers
      of the adrenal medulla and its innervation, including various neuropeptides,
      chromogranin B, secretogranin II, amine transporters, the catecholamine
      synthesizing enzymes tyrosine hydroxylase and PNMT, synaptophysin, and L1,
      essentially were unchanged. Interestingly, AChE immunoreactivity appeared
      unaltered, too. Preganglionic sympathetic neurons, in contrast to adrenal
      medullary cells, do not express TrkA. They must, therefore, be affected
      indirectly by the TrkA knock-out, possibly via a retrograde signal from
      chromaffin cells. Our results suggest that signaling via TrkA, but not TrkB, may
      be involved in the postnatal regulation of AChE activity in the adrenal medulla
      and its preganglionic nerves.

PMID- 8994045
TI  - Kinetics, Ca2+ dependence, and biophysical properties of integrin-mediated
      mechanical modulation of transmitter release from frog motor nerve terminals.
AB  - Neurotransmitter release from frog motor nerve terminals is strongly modulated by
      change in muscle length. Over the physiological range, there is an approximately
      10% increase in spontaneous and evoked release per 1% muscle stretch. Because
      many muscle fibers do not receive suprathreshold synaptic inputs at rest length,
      this stretch-induced enhancement of release constitutes a strong peripheral
      amplifier of the spinal stretch reflex. The stretch modulation of release is
      inhibited by peptides that block integrin binding of natural ligands. The
      modulation varies linearly with length, with a delay of no more than
      approximately 1-2 msec and is maintained constant at the new length. Moreover,
      the stretch modulation persists in a zero Ca2+ Ringer and, hence, is not
      dependent on Ca2+ influx through stretch activated channels. Eliminating
      transmembrane Ca2+ gradients and buffering intraterminal Ca2+ to approximately
      normal resting levels does not eliminate the modulation, suggesting that it is
      not the result of release of Ca2+ from internal stores. Finally, changes in
      temperature have no detectable effect on the kinetics of stretch-induced changes
      in endplate potential (EPP) amplitude or miniature EPP (mEPP) frequency. We
      conclude, therefore, that stretch does not act via second messenger pathways or a
      chemical modification of molecules involved in the release pathway. Instead,
      there is direct mechanical modulation of release. We postulate that tension on
      integrins in the presynaptic membrane is transduced mechanically into changes in
      the position or conformation of one or more molecules involved in
      neurotransmitter release, altering sensitivity to Ca2+ or the equilibrium for a
      critical reaction leading to vesicle fusion.

PMID- 8994046
TI  - Visual pigment assignments in regenerated retina.
AB  - Retinas of adult teleost fish can regenerate after injury. Two important issues
      regarding this phenomenon are the assembly of the regenerated retina and the
      neuronal images of the visual scene that the regenerated retina produces. Here we
      report experiments in which the visual pigment content of photoreceptors derived
      from native and regenerated sunfish retinas was determined by
      microspectrophotometry. In native retina, there is an apparently perfect
      correspondence between cone morphology and visual pigment content; all rods
      contain a middle-wavelength pigment, all single cones contain a different middle
      wavelength pigment, and all double cone members contain a long-wavelength
      pigment. The visual pigments in regenerated rods and double cones were the same
      as in native retina; however, triple cones, a morphology never observed in native
      retina, contained the long-wavelength pigment. Moreover, although approximately
      60% of regenerated single cones contained the expected middle-wavelength pigment,
      all other single cones contained the long-wavelength pigment. This mismatch
      between morphology of regenerated single cones and their visual pigment
      assignment indicated the following: (1) There is a degree of independence between
      the mechanisms that establish cone morphology and pigment content during
      regeneration, which suggests that cone photoreceptor regeneration is not a
      straightforward recapitulation of the normal cone photoreceptor developmental
      plan. (2) Although anomalous, the long-wavelength single cones may enable
      regenerated retina to restore the native spectral sampling of the visual scene.

PMID- 8994047
TI  - Overexpression of Ca2+/calmodulin-dependent protein kinase II in PC12 cells
      alters cell growth, morphology, and nerve growth factor-induced differentiation.
AB  - To examine the role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in
      cell differentiation and neuronal functions, stable transformants of PC12 cells
      were established that expressed levels of the alpha-subunit of CaMKII (alpha
      CaMKII) equivalent to mammalian neurons. The expression of the transfected alpha
      CaMKII gene or the endogenous beta CaMKII gene was monitored by RNase protection
      assays, and alpha CaMKII protein expression was determined by Western blots.
      Several PC12-derived clones expressed amounts of alpha CaMKII mRNA and alpha
      CaMKII protein similar to that of hippocampal tissues and several orders of
      magnitude greater than untransfected PC12 cells. CaMKII catalytic activity was
      four times higher in extracts from alpha CaMKII-overexpressing compared with
      untransfected PC12 cells. All clones overexpressing alpha CaMKII displayed
      altered cellular growth and adhesion properties including increased cell-to
      substrate adhesion, decreased cell-to-cell adhesion, enhanced contact inhibition,
      and prolonged survival at confluency. Furthermore, the alpha CaMKII activity in
      overexpressing PC12 cells inhibited neurite elongation during NGF-induced
      differentiation. Inhibition of CaMKII activity in vivo with KN-62 caused the
      morphological phenotypes of alpha CaMKII-overexpressing cells to partially revert
      to that of untransfected PC12 cells. These results show that alpha CaMKII
      catalytic activity affects growth, morphology, and NGF-induced differentiation of
      PC12 cells.

PMID- 8994048
TI  - Neuronal regulation of glutamate transporter subtype expression in astrocytes.
AB  - GLT-1, GLAST, and EAAC1 are high-affinity, Na(+)-dependent glutamate transporters
      identified in rat forebrain. The expression of these transporter subtypes was
      characterized in three preparations: undifferentiated rat cortical astrocyte
      cultures, astrocytes cocultured with cortical neurons, and astrocyte cultures
      differentiated with dibutyryl cyclic AMP (dBcAMP). The undifferentiated astrocyte
      monocultures expressed only the GLAST subtype. Astrocytes cocultured with neurons
      developed a stellate morphology and expressed both GLAST and GLT-1; neurons
      expressed only the EAAC1 transporter, and rare microglia in these cultures
      expressed GLT-1. Treatment of astrocyte cultures with dBcAMP induced expression
      of GLT-1 and increased expression of GLAST. These effects of dBcAMP on
      transporter expression were qualitatively similar to those resulting from
      coculture with neurons, but immunocytochemistry showed the pattern of transporter
      expression to be more complex in the coculture preparations. Compared with
      astrocytes expressing only GLAST, the dBcAMP-treated cultures expressing both
      GLAST and GLT-1 showed an increase in glutamate uptake Vmax, but no change in the
      glutamate K(m) and no increased sensitivity to inhibition by dihydrokainate.
      Pyrrolidine-2,4-dicarboxylic acid and threo-beta-hydroxyaspartic acid caused
      relatively less inhibition of transport in cultures expressing both GLAST and GLT
      1, suggesting a weaker effect at GLT-1 than at GLAST. These studies show that
      astrocyte expression of glutamate transporter subtypes is influenced by neurons,
      and that dBcAMP can partially mimic this influence. Manipulation of transporter
      expression in astrocyte cultures may permit identification of factors regulating
      the expression and function of GLAST and GLT-1 in their native cell type.

PMID- 8994049
TI  - N-ethylmaleimide blocks depolarization-induced suppression of inhibition and
      enhances GABA release in the rat hippocampal slice in vitro.
AB  - Regulation of synaptic, GABAA receptor-mediated inhibition is a process of
      critical importance to normal brain function. Recently, we have described a
      phenomenon in hippocampus of a transient, yet marked, decrease in spontaneous,
      GABAA receptor-mediated IPSCs after depolarization activated Ca2+ influx into a
      pyramidal cell. This process, depolarization-induced suppression of inhibition
      (DSI), is absent in hippocampal cells that previously had been exposed to
      pertussis toxin in vivo, implicating a G-protein in the DSI process. To
      circumvent the problem that a single cell cannot be studied before and after G
      protein block using the pertussis toxin pretreatment method, we have used the
      sulfhydryl alkylating agent N-ethylmaleimide (NEM), which blocks pertussis toxin
      sensitive G-proteins, to determine whether acute inhibition of G-proteins can
      eliminate DSI of spontaneous IPSCs (sIPSCs). In whole-cell recordings from CA1
      pyramidal cells that were first determined to express DSI, we have found that NEM
      does block DSI of sIPSCs. We also report that DSI of monosynaptic, evoked IPSCs
      is blocked by NEM, suggesting that a similar mechanism underlies both forms of
      DSI. It was of interest that DSI was abolished at a time when NEM had increased,
      not decreased, GABA transmission. Indeed, NEM greatly increased quantal GABA
      release by a Ca(2+)-independent mechanism, an observation with potentially
      important implications for understanding synaptic GABA release.

PMID- 8994050
TI  - Calpain activation contributes to dendritic remodeling after brief excitotoxic
      injury in vitro.
AB  - The calcium-dependent protease calpain may contribute to neuronal death in acute
      neurological insults and may be activated very early in the neuronal injury
      cascade. We assessed the role of calpain in a model of rapid, reversible
      dendritic injury in murine cortical cultures. Brief sublethal NMDA exposure (10
      30 microM for 10 min) resulted in focal swellings, or varicosities, along the
      length of neuronal dendrites as visualized with the lipophilic membrane tracer
      Dil or with immunostaining using antibodies to the somatodendritic protein MAP2.
      These varicosities appeared within minutes of NMDA exposure and recovered
      spontaneously within 2 hr after NMDA removal. Addition of the calpain inhibitors
      MDL28,170, calpain inhibitors I and II, and leupeptin (all 1-100 microM) had
      little effect on the development of NMDA-induced dendrite injury. However, the
      resolution of varicosities was substantially delayed by addition of calpain
      inhibitors after sublethal excitotoxic exposure. Using Western blots and
      immunocytochemistry, we observed reactivity for a calpain-specific spectrin
      proteolytic fragment during the period of recovery from dendritic swelling, but
      not during its formation. Spectrin breakdown product immunoreactivity could be
      blocked by the calpain inhibitor MDL28,170 and appeared in neuronal cell bodies
      and neurites in a time course that paralleled dendritic recovery. These
      observations suggest that calcium-dependent proteolysis contributes to recovery
      of dendritic structure after NMDA exposure. Calpain activation is not necessarily
      detrimental and may play a role in dendritic remodeling after neuronal injury.

PMID- 8994051
TI  - Multiple ionic conductances of the human dopamine transporter: the actions of
      dopamine and psychostimulants.
AB  - Electrophysiological and pharmacological studies of a cloned human dopamine
      transporter (hDAT) were undertaken to investigate the mechanisms of transporter
      function and the actions of drugs at this target. Using two-electrode voltage
      clamp techniques with hDAT-expressing Xenopus laevis oocytes, we show that hDAT
      can be considered electrogenic by two criteria. (1) Uptake of hDAT substrates
      gives rise to a pharmacologically appropriate "transport-associated" current. (2)
      The velocity of DA uptake measured in oocytes clamped at various membrane
      potentials was voltage-dependent, increasing with hyperpolarization. Concurrent
      measurement of transport-associated current and substrate flux in individual
      oocytes revealed that charge movement during substrate translocation was greater
      than would be expected for a transport mechanism with fixed stoichiometry of 2
      Na+ and 1 Cl- per DA+ molecule. In addition to the transport-associated current,
      hDAT also mediates a constitutive leak current, the voltage and ionic
      dependencies of which differ markedly from those of the transport-associated
      current. Ion substitution experiments suggest that alkali cations and protons are
      carried by the hDAT leak conductance. In contrast to the transport-associated
      functions, the leak does not require Na+ or Cl-, and DAT ligands readily interact
      with the transporter even in the absence of these ions. The currents that hDAT
      mediates provide a functional assay that readily distinguishes the modes of
      action of amphetamine-like "DA-releasing" drugs from cocaine-like translocation
      blockers. In addition, the voltage dependence of DA uptake suggests a mechanism
      through which presynaptic DA autoreceptor activation may accelerate the
      termination of dopaminergic neurotransmission in vivo.

PMID- 8994052
TI  - Tumor necrosis factor enhances the capsaicin sensitivity of rat sensory neurons.
AB  - The capacity of the proinflammatory cytokines, tumor necrosis factor alpha (TNF
      alpha) and interleukin 1 beta (IL-1 beta), to modulate the sensitivity of
      isolated sensory neurons grown in culture to the excitatory chemical agent
      capsaicin was examined. Alterations in capsaicin sensitivity were assessed by
      quantifying the number of neurons labeled with cobalt after exposure to capsaicin
      and by recording the whole-cell response from a single neuron to the focal
      application of capsaicin. A 24 hr pretreatment of the neuronal cultures with TNF
      alpha (10 or 50 ng/ml), but not IL-1 beta (10 or 50 ng/ml), produced a
      concentration-dependent increase in the number of cobalt-labeled neurons after
      exposure to 100 nM capsaicin. The peak increase in the number of labeled neurons
      was attained after a 4 hr treatment with 10 ng/ml TNF alpha. Similarly,
      pretreatment with TNF alpha (10 ng/ml for 4, 12, and 24 hr) produced a greater
      than twofold increase in the average peak amplitude of the inward current evoked
      by 100 nM capsaicin. Both the TNF alpha-induced increase in labeling and current
      amplitude were blocked by treating the neuronal cultures with indomethacin before
      the addition of TNF alpha. Enhancement of the capsaicin-evoked current also was
      blocked by the specific cyclo-oxygenase-2 inhibitor SC-236. These results
      indicate that TNF alpha can enhance the sensitivity of sensory neurons to the
      excitation produced by capsaicin and that this enhancement likely is mediated by
      the neuronal production of prostaglandins. Isolated sensory neurons grown in
      culture may prove to be a useful model system in which to explore how prolonged
      exposure to mediators associated with chronic inflammation alter the regulatory
      pathways that modulate the excitability of the nervous system.

PMID- 8994053
TI  - Epileptogenesis in vivo enhances the sensitivity of inhibitory presynaptic
      metabotropic glutamate receptors in basolateral amygdala neurons in vitro.
AB  - Modulation of excitatory synaptic transmission by presynaptic metabotropic
      glutamate receptors (mGluRs) was examined in brain slices from control rats and
      rats with amygdala-kindled seizures. Using whole-cell voltage-clamp and current
      clamp recordings, this study shows for the first time that in control and kindled
      basolateral amygdala neurons, two pharmacologically distinct presynaptic mGluRs
      mediate depression of synaptic transmission. Moreover, in kindled neurons,
      agonists at either group II- or group III-like mGluRs exhibit a 28- to 30-fold
      increase in potency and suppress synaptically evoked bursting. The group II mGluR
      agonist (2S,3S,4S)-2-(carboxycyclopropyl)glycine (L-CCG) dose-dependently
      depressed monosynaptic EPSCs evoked by stimulation in the lateral amygdala with
      EC50 values of 36 nM (control) and 1.2 nM (kindled neurons). The group III mGluR
      agonist L-2-amino-4-phosphonobutyrate (L-AP4) was less potent, with EC50 values
      of 297 nM (control) and 10.8 nM (kindled neurons). The effects of L-CCG and L-AP4
      were fully reversible. Neither L-CCG (0.0001-10 microM) nor L-AP4 (0.001-50
      microM) caused membrane currents or changes in the current-voltage relationship.
      The novel mGluR antagonists (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine
      (MCCG; 100 microM) and (S)-2-methyl-2-amino-4-phosphonobutyrate (MAP4; 100
      microM) selectively reversed the inhibition by L-CCG and L-AP4 to 81.3 +/- 12%
      and 65.3 +/- 6.6% of predrug, respectively. MCCG and MAP4 (100-300 microM)
      themselves did not significantly affect synaptic transmission. The exquisite
      sensitivity of agonists in the kindling model of epilepsy and the lack of
      evidence for endogenous receptor activation suggest that presynaptic group II-
      and group III-like mGluRs might be useful targets for suppression of excessive
      synaptic activation in neurological disorders such as epilepsy.

PMID- 8994054
TI  - Actions of the ORL1 receptor ligand nociceptin on membrane properties of rat
      periaqueductal gray neurons in vitro.
AB  - The actions of the endogenous ORL1-receptor ligand nociceptin on the membrane
      properties and synaptic currents in rat periaqueductal gray (PAG) neurons were
      examined by the use of whole-cell patch-clamp recording in brain slices.
      Nociceptin produced an outward current in all neurons tested, with an EC50 of 39
      +/- 7 nM. The outward current was unaffected by naloxone. Outward currents
      reversed polarity at -110 +/- 3 mV in 2.5 mM extracellular potassium, and the
      reversal potential increased when the extracellular potassium concentration was
      raised (slope = 66.3 mV/log[K+]o mM). Thus, the nociceptin-induced outward
      current was attributable to an increased K+ conductance. Nociceptin inhibited
      evoked fast GABAergic (IP-SCs) and glutamatergic (EPSCs) postsynaptic currents
      and increased paired-pulse facilitation in a subpopulation of PAG neurons.
      Nociceptin inhibited evoked IPSCs and EPSCs in approximately 50% of neurons
      throughout the PAG, except in the ventrolateral PAG, where nociceptin inhibited
      evoked IPSCs in most neurons. Nociceptin decreased the frequency of spontaneous
      miniature postsynaptic currents (mIPSCs and mEPSCs) in a subpopulation of PAG
      neurons but had no effect on their amplitude distributions. Thus, nociceptin had
      a presynaptic inhibitory effect on transmitter release. These findings suggest
      that nociceptin, via its pre- and postsynaptic actions, has the potential to
      modulate the analgesic, behavioral, and autonomic functions of the PAG.

PMID- 8994056
TI  - Mediation by protein kinases C and A of Go-linked slow responses of enteric
      neurons to 5-HT.
AB  - 5-HT activates the peristaltic reflex and is the neurotransmitter of a subset of
      myenteric interneurons. Hyperpolarizing afterpotential (AH)/type 2 neurons
      respond to 5-HT with a long-lived depolarization that is caused by the inhibition
      of a Ca(2+)-activated K+ conductance (gKCa). This effect is mediated by a G
      protein-coupled receptor, 5-HT1P. 5-HT1P agonists specifically activate G alpha
      o, the immunoreactivity of which was found to be highly abundant and membrane
      associated in almost all enteric neurons. Responses of hyperpolarizing AH/type 2
      neurons to 5-HT were inhibited by intracellular injection of GDP beta S or anti-G
      alpha o Fab fragments but were potentiated and prolonged by intracellular GTP
      gamma S. Responses to 5-HT were antagonized by pertussis toxin, downregulation of
      protein kinase C (PKC) and inhibitors of phosphatidylcholine phospholipase C (PC
      PLC), PKC (including pseudosubstrate peptides, chelerythrine, and the alpha/beta
      isoform-specific inhibitor Go 6976), protein kinase A (PKA), and adenylate
      cyclase. Responses to 5-HT were mimicked by activators of PKC, and 5-HT induced a
      concentration-dependent increase in the membrane-associated PKC activity in
      isolated myenteric ganglia. Immunocytochemical studies suggested that the most
      abundant isoforms of PKC in enteric neurons are alpha and delta. These data
      suggest that signal transduction of the 5-HT1P-mediated slow response to 5-HT
      involves activation of PC-PLC by G alpha o to liberate diacylglycerol, which
      stimulates PKC (most likely alpha). PKC probably activates adenylate cyclase,
      which through cAMP, activates PKA. Activation of both PKA and PKC lead to closure
      of gKCa.

PMID- 8994055
TI  - Cell surface amyloid beta-protein precursor colocalizes with beta 1 integrins at
      substrate contact sites in neural cells.
AB  - Amyloid beta-protein (A beta), the principal constituent of the senile plaques
      seen in Alzheimer's disease (AD), is derived by proteolysis from the beta-amyloid
      precursor protein (beta PP). The distribution and trafficking of cell surface
      beta PP are of particular interest because some of these molecules are direct
      precursors of secreted A beta and because the localization of beta PP at the cell
      surface may be related directly to its physiological functions. Recently, we
      reported that, in cultured hippocampal neurons, cell surface beta PP is
      preferentially expressed on axons in a striking discontinuous pattern. In this
      study, we describe the colocalization of cell surface beta PP and integrins in
      primary cultured cells. In rat hippocampal neurons, cell surface beta PP was
      colocalized selectively with alpha 1 beta 1 and alpha 5 beta 1 integrin
      heterodimers at these characteristic segmental locations. In rat cortical
      astrocytes, both cell surface beta PP and beta 1 integrin were located at the
      cell periphery in the "spreading" stage shortly after plating. In "flattened"
      astrocytes cultured for several days, beta PP was found in punctate deposits
      called point contacts. In these sites, beta PP was colocalized with alpha 1 beta
      1, but not with alpha 5 beta 1 integrin heterodimers, the latter of which were
      situated at focal contact sites. In both neurons and astrocytes examined after
      shearing, clathrin and alpha-adaptin were colocalized with beta PP on the surface
      that directly contacts the substratum. These results are consistent with the
      putative role of beta PP in cell adhesion and suggests that beta PP either
      interacts with selected integrins or shares similar cellular machinery to promote
      cell adhesion.

PMID- 8994057
TI  - GABAB receptor-mediated inhibition of tetrodotoxin-resistant GABA release in
      rodent hippocampal CA1 pyramidal cells.
AB  - Tight-seal whole-cell recordings from CA1 pyramidal cells of rodent hippocampus
      were performed to study GABAB receptor-mediated inhibition of tetrodotoxin (TTX)
      resistant IP-SCs. IPSCs were recorded in the presence of TTX and glutamate
      receptor antagonists. (R)-(-)-baclofen reduced the frequency of TTX-resistant
      IPSCs by a presynaptic action. The inhibition by (R)-(-)-baclofen was
      concentration-dependent, was not mimicked by the less effective enantiomer (S)
      (+)-baclofen, and was blocked by the GABAB receptor antagonist CGP 55845A,
      suggesting a specific effect on GABAB receptors. The inhibition persisted in the
      presence of the Ca2+ channel blocker Cd2+. There was no requirement for an
      activation of K+ conductances by (R)-(-)-baclofen, because the inhibition of TTX
      resistant IPSCs persisted in Ba2+ and Cd2+. Because the time courses of TTX
      resistant IPSCs were not changed by (R)-(-)-baclofen, there was no evidence for a
      selective inhibition of quantal release from a subgroup of GABAergic terminals.
      (R)-(-)-baclofen reduced the frequency of TTX-resistant IPSCs in guinea pigs and
      Wistar rats, whereas the inhibition was much smaller in Sprague Dawley rats. In
      Cd2+ and Ba2+, beta-phorbol-12,13-dibutyrate and forskolin enhanced the frequency
      of TTX-resistant IPSCs. Only beta-phorbol-12, 13-dibutyrate reduced the
      inhibition by (R)-(-)-baclofen. We conclude that GABAB receptors inhibit TTX
      resistant GABA release through a mechanism independent from the well known
      effects on Ca2+ or K+ channels. The inhibition of quantal GABA release can be
      reduced by an activator of protein kinase C.

PMID- 8994058
TI  - Neuropathology of degenerative cell death in Caenorhabditis elegans.
AB  - In Caenorhabditis elegans necrosis-like neuronal death is induced by gain-of
      function (gf) mutations in two genes, mec-4 and deg-1, that encode proteins
      similar to subunits of the vertebrate amiloride-sensitive epithelial Na+ channel.
      We have determined the progress of cellular pathology in dying neurons via light
      and electron microscopy. The first detectable abnormality is an infolding of the
      plasma membrane and the production of small electron-dense whorls. Later,
      cytoplasmic vacuoles and larger membranous whorls form, and the cell swells. More
      slowly, chromatin aggregates and the nucleus invaginates. Mitochondria and Golgi
      are not dramatically affected until the final stages of cell death when
      organelles, and sometimes the cells themselves, lyse. Certain cells, including
      some muscle cells in deg-1 animals, express the abnormal gene products and
      display a few membrane abnormalities but do not die. These cells either express
      the mutant genes at lower levels, lack other proteins needed to form
      inappropriately functioning channels, or are better able to compensate for the
      toxic effects of the channels. Overall, the ultrastructural changes in these
      deaths suggest that enhanced membrane cycling precedes vacuolation and cell
      swelling. The pathology of mec-4(gf) and deg-1(gf) cells shares features with
      that of genetic disorders with alterations in channel subunits, such as
      hypokalemic periodic paralysis in humans and the weaver mouse, and with
      degenerative conditions, e.g., acute excitotoxic death. The initial pathology in
      all of these conditions may reflect attempts by affected cells to compensate for
      abnormal membrane proteins or functions.

PMID- 8994059
TI  - Amyloid beta-peptide impairs glucose transport in hippocampal and cortical
      neurons: involvement of membrane lipid peroxidation.
AB  - A deficit in glucose uptake and a deposition of amyloid beta-peptide (A beta)
      each occur in vulnerable brain regions in Alzheimer's disease (AD). It is not
      known whether mechanistic links exist between A beta deposition and impaired
      glucose transport. We now report that A beta impairs glucose transport in
      cultured rat hippocampal and cortical neurons by a mechanism involving membrane
      lipid peroxidation. A beta impaired 3H-deoxy-glucose transport in a concentration
      dependent manner and with a time course preceding neurodegeneration. The decrease
      in glucose transport was followed by a decrease in cellular ATP levels.
      Impairment of glucose transport, ATP depletion, and cell death were each
      prevented in cultures pretreated with antioxidants. Exposure to FeSO4, an
      established inducer of lipid peroxidation, also impaired glucose transport.
      Immunoprecipitation and Western blot analyses showed that exposure of cultures to
      A beta induced conjugation of 4-hydroxynonenal (HNE), an aldehydic product of
      lipid peroxidation, to the neuronal glucose transport protein GLUT3. HNE induced
      a concentration-dependent impairment of glucose transport and subsequent ATP
      depletion. Impaired glucose transport was not caused by a decreased energy demand
      in the neurons, because ouabain, which inhibits Na+/K(+)-ATPase activity and
      thereby reduces neuronal ATP hydrolysis rate, had little or no effect on glucose
      transport. Collectively, the data demonstrate that lipid peroxidation mediates A
      beta-induced impairment of glucose transport in neurons and suggest that this
      action of A beta may contribute to decreased glucose uptake and neuronal
      degeneration in AD.

PMID- 8994060
TI  - Role of NMDA and non-NMDA ionotropic glutamate receptors in traumatic spinal cord
      axonal injury.
AB  - We examined the role of glutamatergic mechanisms in acute injury to rat spinal
      cord white matter. Compound action potentials (CAPs) were recorded from isolated
      dorsal column segments in vitro. Under control conditions (Ringer's solution),
      the CAPs decreased to 71.4 +/- 2.0% of preinjury values after compression injury
      with a clip exerting a closing force of 2 g. The combination of the NMDA receptor
      blocker APV (50 microM) and the AMPA/kainate (KA) receptor blocker CNQX (10
      microM) resulted in significantly improved recovery of CAP amplitude postinjury;
      however, the NMDA receptor antagonist APV alone did not enhance postinjury
      recovery, and infusion of NMDA (10 microM) did not affect recovery of the CAPs.
      In contrast, the AMPA/KA receptor blockers NBQX (10 microM) or CNQX (10 microM)
      significantly enhanced the recovery of CAP amplitude postinjury. The agonists
      AMPA (100 microM) or KA (100 microM) resulted in significant attenuation of CAP
      amplitude postinjury. Coapplication of AMPA/KA plus NBQX and CNQX was also
      associated with improved functional recovery. After incubation with AMPA and KA,
      Co(2+)-positive glia were visualized in spinal cord white matter. Similar results
      were seen after compressive injury but not in control cords. Immunohistochemistry
      and Western blot analysis demonstrated AMPA (GluR4)- and KA (GluR6/7 and KA2)
      positive astrocytes in spinal cord white matter. In summary, non-NMDA ionotropic
      glutamate receptors seem to be involved in the pathophysiology of traumatic
      spinal cord injury. The presence of AMPA (GluR4) and KA (GluR6/7 and KA2)
      receptors on periaxonal astrocytes suggests a role for these cells in
      glutamatergic white matter injury.

PMID- 8994061
TI  - Selective degeneration fo Purkinje cells with Lewy body-like inclusions in aged
      NFHLACZ transgenic mice.
AB  - Transgenic (NFHLacZ) mice expressing a fusion protein composed of a truncated
      high-molecular-weight mouse neurofilament (NF) protein (NFH) fused to beta
      galactosidase (LacZ) develop inclusions in neurons throughout the CNS. These
      inclusions persist from birth to advanced age and contain massive filamentous
      aggregates including all three endogenous NF proteins and the NFHLacZ fusion
      protein. Further, the levels of endogenous NF proteins are selectively reduced in
      NFHLacZ mice. Because these inclusions resemble NF-rich Lewy bodies (LBs) in
      Parkinson's disease and LB dementia, we asked whether these lesions compromised
      the viability of affected neurons during aging. We studied hippocampal CA1
      neurons, nearly all of which harbored inclusions (type I) devoid of cellular
      organelles, and cerebellar Purkinje cells, nearly all of which accumulated
      inclusions (type II) containing numerous entrapped organelles. Purkinje cells
      with type II inclusions began to degenerate in the NFHLacZ mice at approximately
      1 year of age, and most were eliminated by 18 months of age. In contrast, there
      was no significant loss of type I inclusion-bearing CA1 neurons with age. These
      data suggest that the sequestration of cellular organelles in type II inclusions
      may isolate and impair the function of these organelles, thereby rendering
      Purkinje cells selectively vulnerable to degeneration with age as in
      neurodegenerative diseases of the elderly characterized by accumulation of LBs.

PMID- 8994062
TI  - Apoptosis and its relation to the cell cycle in the developing cerebral cortex.
AB  - Large numbers of dying cells are found in proliferating tissues, suggesting a
      link between cell death and cell division. We detected and quantified dying cells
      during pre- and early postnatal development of the rat cerebral cortex using in
      situ end labeling of DNA fragmentation [terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labeling (TUNEL)] and electron microscopy. The
      proliferative zones that give rise to the neuronal and glial cell types of the
      cortex, the ventricular and, to a larger extent, the subventricular zones showed
      higher incidence of cell death than other regions of the developing cortex during
      the period of neurogenesis. Gel electrophoresis of DNA isolated from the
      subventricular zone of newborn animals showed a ladder pattern that is
      characteristic of apoptosis. The number of apoptotic cells remained high in this
      zone for at least 2 weeks, during which period cells continued to divide. The
      correlation between cell division and cell death was studied in the
      subventricular zone of newborn rats; cumulative labeling with bromodeoxyuridine
      showed that 71% of TUNEL-labeled cells had taken up this S-phase marker before
      undergoing cell death. Using bromodeoxyuridine and [3H]-thymidine in succession
      to identify a cohort of proliferating cells, we found that the clearance time of
      TUNEL-positive nuclei was 2 hr and 20 min. A comparison between the number of
      mitotic figures and that of TUNEL-positive nuclei showed that cell death affects
      one in every 14 cells produced by dividing ventricular zone cells at embryonic
      day 16 and one in every 1.5 cells produced in the subventricular zone of newborn
      rats. In addition, we found that most of TUNEL-positive cells were in the G1
      phase of their cell cycle. We conclude that apoptosis is prominent in the
      proliferating neuroepithelium of the developing rat cerebral cortex and that it
      is related to the progression of the cell cycle.

PMID- 8994063
TI  - Growth cone form is behavior-specific and, consequently, position-specific along
      the retinal axon pathway.
AB  - Video time-lapse microscopy has made it possible to document growth cone motility
      during axon navigation in the intact brain. This approach prompted us to
      reanalyze the hypothesis, originally derived from observations of fixed tissue,
      that growth cone form is position-specific. The behaviors of Dil-labeled retinal
      axon growth cones were tracked from retina through the optic tract in mouse brain
      at embryonic day (E) 15-17, and these behaviors were matched with different
      growth cone forms. Patterns of behavior were then analyzed in the different
      locales from the retina through the optic tract. Throughout the pathway, episodes
      of advance were punctuated by pauses in extension. Irrespective of locale,
      elongated streamlined growth cones mediated advance and complex forms developed
      during pauses. The rate of advance and the duration of pauses were surprisingly
      similar in different parts of the pathway. In contrast, the duration of periods
      of advance was more brief in the chiasm compared to those in the optic nerve and
      tract. Consequently, in the chiasm, growth cones spent relatively more time
      pausing and less time advancing than in the optic nerve or tract. Thus, because
      growth cone form is behavior-specific and certain behaviors predominate in
      particular loci, growth cone form appears to be position-specific in static
      preparations, due to the fraction of time spent in a given state in different
      locales.

PMID- 8994064
TI  - Novel modulatory effect of L-type calcium channels at newly formed neuromuscular
      junctions.
AB  - This study aimed to examine changes of presynaptic voltage-sensitive calcium
      channel (VSCC) subtypes during synapse formation and regeneration in relation to
      transmitter release at the neuromuscular junction (NMJ). Synaptic potentials were
      recorded from developing rat NMJs and from regenerating mouse and frog NMJs. As
      in normal adult NMJs, evoked transmitter release was reduced by an N-type VSCC
      blocker in the frog and by a P/Q-type VSCC blocker in the mammal at immature
      NMJs; however, various L-type VSCC blockers, both dihydropyridine and
      nondihydropyridine antagonists, increased evoked but not spontaneous release in a
      dose-dependent manner at newly formed NMJs. This presynaptic potentiation
      disappeared as NMJs matured. A rapid intracellular Ca2+ buffer, bis(O
      aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid-AM, prevented the potentiation
      effect of nifedipine, but a slow Ca2+ buffer, EGTA-AM, did not. Thus, the
      potentiation effect of L-type blockers requires Ca2+ transients. Pretreatment
      with Ca2(+)-activated K+ channel blockers, iberiotoxin or charybdotoxin, did not
      prevent potentiation by nifedipine at regenerating frog NMJs. Thus, Ca(2+)
      activated K+ channels were not likely involved in this potentiation. In contrast,
      no additional potentiation by nifedipine was seen in muscles pretreated with
      pertussis toxin (PTX), a G-protein blocker, which by itself enhances evoked
      transmitter release at regenerating frog NMJs. These results suggest the
      existence of multiple subtypes of VSCCs at newly formed motor nerve terminals. In
      addition to the normal N- or P/Q-type VSCCs that mediate transmitter release, L
      type VSCCs may play a novel modulatory role in evoked transmitter release by
      activating a mechanism linked to PTX-sensitive G-proteins during synapse
      maturation.

PMID- 8994065
TI  - Maternal cocaine treatment alters dynorphin and enkephalin mRNA expression in
      brains of fetal rhesus macaques.
AB  - Cocaine exposure in utero is known to cause a variety of behavioral and motor
      deficits that may be attributable to alterations in the dopamine neurocircuitry.
      To ascertain cocaine effects in the fetus, we developed a nonhuman primate model
      in which pregnant monkeys were administered cocaine from day 20 through day 60 or
      70 of gestation. Fetuses from these pregnancies develop a repertoire of neural
      deficiencies, including decreased mRNA expression of tyrosine hydroxylase in the
      midbrain and increased mRNA expression of dopamine receptor subtypes in the
      rostral forebrain. Presently, we studied the effects of maternal cocaine
      treatment on the mRNA expression of the endogenous opioids preprodynorphin (PPD)
      and preproenkephalin (PPE) in fetal monkey brains. Fetuses exposed to saline
      (0.9%) or cocaine (3 mg/kg) were delivered by Caesarean section, the fetal brains
      were dissected, and tissue RNA was extracted and quantified using ribonuclease
      protection assay analysis. The opioid peptides PPD and PPE were expressed in the
      fetal monkey brain by day 60, and even higher levels were found in day 70
      fetuses. Maternal exposure to cocaine increased gene expression of PPD and PPE in
      the fetus at both day 60 and day 70 of gestation. Dynorphin mRNA levels were
      significantly elevated in the striatum, whereas enkephalin mRNA was elevated in
      both the frontal cortex and the striatal area of fetuses whose mothers received
      cocaine. Changes in the expression of these opioid peptides in presumed dopamine
      target neurons, which mediate motivation and reward, as well as motor control,
      provide further evidence for profound consequences of in utero cocaine exposure
      on the developing dopamine neurocircuitry.

PMID- 8994066
TI  - Estrogen induces axonal outgrowth in the nucleus retroambiguus-lumbosacral
      motoneuronal pathway in the adult female cat.
AB  - In 1995, we discovered a new pathway in the cat, which originates from the
      nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral
      hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VGJM,
      Holstege G (1995) Caudal medullary pathways to lumbosacral motoneuronal cell
      groups in the cat: evidence for direct projections possibly representing the
      final common pathway for lordosis. J Comp Neurol 359:457-475]. The NRA is a
      compact group of interneurons located laterally in the caudal medulla oblongata.
      Its projection to lumbosacral motoneurons is thought to represent the final
      common pathway for male mounting and for female receptive or lordosis behavior.
      However, females only display lordosis behavior. However, females only display
      lordosis behavior when they are in estrus, which suggests that the NRA
      lumbosacral pathway is only active during estrus. This raised the question of
      whether estrogen affects this pathway. The effect of estrogen on the NRA
      lumbosacral projection was studied light microscopically, using wheat-germ
      agglutinin horseradish peroxidase (WGA-HRP) as a tracer. The rubrospinal pathway
      served as control. The density of labeled NRA fibers in their target hindlimb
      motoneuronal cell groups appeared abundant in estrous and very weak in nonestrous
      cats. Such differences were not found in the rubrospinal pathway. For electron
      microscopical study, the NRA projection to the semi-membranosus motoneuronal cell
      group was selected. In this cell group, an almost ninefold increase of labeled
      profiles was found in estrous versus nonestrous cats. Moreover, the
      semimembranous motoneuronal cell group contained labeled growth cones in estrous,
      but not in nonestrous, cats. The present study is the first to show that estrogen
      induces axonal outgrowth of a precisely identified pathway in the adult mammalian
      central nervous system. The possible mechanisms underlying this outgrowth are
      discussed.

PMID- 8994067
TI  - Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor
      alpha expression in astrocytes and neurons of the fascia dentata after entorhinal
      cortex lesion.
AB  - Neurotrophic factors have been implicated in reactive processes occurring in
      response to CNS lesions. Ciliary neurotrophic factor (CNTF), in particular, has
      been shown to ameliorate axotomy-induced degeneration of CNS neurons and to be
      upregulated at wound sites in the brain. To investigate a potential role of CNTF
      in lesion-induced degeneration and reorganization, we have analyzed the
      expression of CNTF protein and CNTF receptor alpha (CNTFR alpha) mRNA in the rat
      dentate gyrus after unilateral entorhinal cortex lesions (ECLs), using
      immunocytochemistry and nonradioactive in situ hybridization, respectively. In
      sham-operated as in normal animals, CNTF protein was not detectable by
      immunocytochemistry. Starting at 3 d after ECL, upregulation of CNTF expression
      was observed in the ipsilateral outer molecular layer (OML). Expression was
      maximal at around day 7, and at this stage immunoreactivity could be specifically
      localized to astrocytes in the ipsilateral OML. By day 14 postlesion, CNTF
      immunoreactivity had returned to control levels. CNTFR alpha mRNA was restricted
      to neurons of the granule cell layer in controls. Three days postlesion,
      prominent CNTFR alpha expression was observed in the deafferented OML. A similar
      but less prominent response was noticed in the contralateral OML. After 10 d,
      CNTFR alpha expression had returned to control levels. Double labeling for CNTFR
      alpha mRNA and glial fibrillary acidic protein (GFAP) showed that upregulation of
      CNTFR alpha occurred in reactive, GFAP-immunopositive astrocytes of the OML. A
      substantial reduction of CNTFR alpha expression in the deafferented granule cells
      was transiently observed at 7 and 10 d postlesion. Our results suggest a
      paracrine or autocrine function of CNTF in the regulation of astrocytic and
      neuronal responses after brain injury.

PMID- 8994068
TI  - Song- and order-selective neurons in the songbird anterior forebrain and their
      emergence during vocal development.
AB  - Auditory experience is critical for vocal learning in songbirds as in humans.
      Therefore, in a search for neural mechanisms for song learning and recognition,
      the auditory response properties of neurons in the anterior forebrain (AF)
      pathway of the songbird brain were investigated. This pathway plays an essential
      but poorly understood role during the period of song development when auditory
      feedback is most crucial. Single-unit recordings demonstrated that both the
      lateral magnocellular nucleus of the anterior neostriatum (LMAN) and Area X (X)
      contain auditory neurons in adult male finches. These neurons are strongly
      selective for both spectral and temporal properties of song; they respond more
      robustly to the bird's own song (BOS) than to songs of conspecific individuals,
      and they respond less well to the BOS if it is played in reverse. In addition, X
      neurons are more broadly responsive than LMAN neurons, suggesting that responses
      to song become progressively more refined along this pathway. Both X and LMAN of
      young male finches early in the process of song learning (30-45 d old) also
      contain song-responsive auditory neurons, but these juvenile neurons lack the
      song and order selectivity present in adult birds. The spectral and temporal
      selectivity of the adult AF auditory neurons therefore arises during development
      in neurons that are initially broadly song-responsive. These neurons provide one
      of the clearest examples of experience-dependent acquisition of complex stimulus
      selectivity. Moreover, the auditory properties of the AF circuit suggest that one
      of its functions may be to mediate the auditory learning and feedback so
      essential to song development.

PMID- 8994069
TI  - Morphological alterations in the peripheral and central nervous systems of mice
      lacking glial cell line-derived neurotrophic factor (GDNF): immunohistochemical
      studies.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta
      superfamily of growth factors with neurotrophic activity on midbrain dopaminergic
      neurons and on developing and mature motoneurons of the brainstem and spinal
      cord. To investigate the extent of GDNF dependency of central and peripheral
      nervous structures during development, we have performed an immunohistochemical
      analysis of sections from the whole head including brain, peripheral ganglia,
      developing teeth and tongue, as well as intestines, in mutant mice lacking a part
      of the third exon that encodes the GDNF protein. As described previously, these
      null-mutated mice lack most of the enteric nerve plexus and are subject to
      agenesis or severe dysgenesis of the kidneys. In the present communication, we
      examined the development of vibrissae and incisor and molar teeth, as well as the
      innervation of these structures, and found no differences between null-mutated
      and control mice. A decrease in the immunohistochemical labeling intensity with
      tyrosine hydroxylase was observed in the superior cervical ganglion (SCG), as
      well as in the pontine nucleus locus coeruleus, and the sympathetic innervation
      of blood vessels and glands in the head was significantly decreased. None of the
      brain nuclei studied exhibited any significant decreases in the total number of
      neurons, but the packing density of neurons in the nucleus locus coeruleus was
      decreased. These data indicate that GDNF might be one neurotrophic factor that
      contributes to the development of central and peripheral noradrenergic neurons.

PMID- 8994070
TI  - Spatiotemporal patterns of spindle oscillations in cortex and thalamus.
AB  - Spindle oscillations (7-14 Hz) appear in the thalamus and cortex during early
      stages of sleep. They are generated by the combination of intrinsic properties
      and connectivity patterns of thalamic neurons and distributed to cortical
      territories by thalamocortical axons. The corticothalamic feedback is a major
      factor in producing coherent spatiotemporal maps of spindle oscillations in
      widespread thalamic territories. Here we have investigated the spatiotemporal
      patterns of spontaneously occurring and evoked spindles by means of multisite
      field potential and unit recordings in intact cortex and decorticated animals. We
      show that (1) spontaneous spindle oscillations are synchronized over large
      cortical areas during natural sleep and barbiturate anesthesia; (2) under
      barbiturate anesthesia, the cortical coherence is not disrupted by transection of
      intracortical synaptic linkages; (3) in intact cortex animals, spontaneously
      occurring barbiturate spindle sequences occur nearly simultaneously over
      widespread thalamic territories; (4) in the absence of cortex, the spontaneous
      spindle oscillations throughout the thalamus are less organized, but the local
      coherence (within 2-4 mm) is still maintained; and (5) spindling propagation is
      observed in intact cortex animals only when elicited by low intensity cortical
      stimulation, applied shortly before the initiation of a spontaneous spindle
      sequence; propagation velocities are between 1 and 3 mm/sec, measured in the
      anteroposterior axis of the thalamus; increasing the intensity of cortical
      stimulation triggers spindle oscillations, which start simultaneously in all
      leads. We propose that, in vivo, the coherence of spontaneous spindle
      oscillations in corticothalamic networks is attributable to the combined action
      of continuous background corticothalamic input initiating spindle sequences in
      several thalamic sites at the same time and divergent corticothalamic and
      intrathalamic connectivity.

PMID- 8994071
TI  - Microencapsulated Eudragit RS30D-coated controlled-release pellets: the influence
      of dissolution variables and topographical evaluation.
AB  - The air suspension technique was employed to prepare Eudragit RS30D-coated
      controlled-release pellets of salbutamol. Drug release in dissolution studies can
      be dependent on the dissolution method and medium used. Thus, the aim of this
      study was to investigate the influence of various dissolution methods and
      dissolution medium pH values on drug release from a batch of pellets which
      displayed controlled drug-release characteristics over an 8-h period in deionized
      water using the rotating basket method. In vitro testing using the official USP
      XXII (rotating basket and rotating paddle) and non-official (rotating bottle)
      methods showed drug release to be independent of the method used. The prepared
      pellets displayed pH-dependent drug-release characteristics when tested in
      hydrochloric acid (pH 1.5), phosphate buffer (pH 6.8) and deionized water (pH
      7.2). Also, in vitro testing, which exposed the pellets to a changing pH gradient
      that simulated the gastrointestinal pH conditions following oral administration,
      was used to confirm the drug-release characteristics. The results showed
      controlled-release characteristics to be maintained, with the drug being released
      over an 8-h period. Scanning electron microscopic evaluation proved useful in the
      elucidation of the physical characteristics of the controlled-release pellets as
      well as in the identification of a possible mode of drug transfer into the
      dissolution medium.

PMID- 8994072
TI  - Preparation and release properties of biodegradable chitin microcapsules: I.
      Preparation of 6-mercaptopurine microcapsules by phase separation methods.
AB  - Chitin [poly-(N-acetyl-1,4-beta-D-glucopyranosamine)] microcapsules were prepared
      by the simple desolvation and the non-solvent addition phase separation methods.
      In the simple desolvation method, chitin droplets were dropped into the
      desolvation agent (water, ethanol, or acetone) and microcapsules soon formed.
      Several solvent-nonsolvent pairs: N,N-dimethylacetamide (DMAc)-water, DMAc
      ethanol, DMAc-propanol, DMAc-n-butanol, and DMAc-acetone with different
      solubility parameter difference, (delta delta) were chosen to prepare chitin
      microcapsules containing 6-mercaptopurine by using the non-solvent-addition phase
      separation method. The results showed that the surface morphology and release
      behaviour of the microcapsules were greatly affected by different solvent
      nonsolvent pairs. The surface of microcapsules prepared from the system of high
      delta delta was more smooth than those from the systems of low delta delta. The
      drug content using the simple desolvation method increased with decreasing delta
      delta because of the higher film formation rate of the microcapsules. On the
      other hand, the drug content using the nonsolvent addition method was lower than
      that using the simple desolvation method because of the dispersion forces,
      applied by mechanical stirring. Microcapsules prepared by the simple desolvation
      method had a narrower size distribution and larger mean size than those prepared
      by the nonsolvent addition method.

PMID- 8994074
TI  - In vitro biodegradation of polyhydroxybutyrate-hydroxyvalerate microcapsules
      exposed to Hank's buffer, newborn calf serum, pancreatin and synthetic gastric
      juice.
AB  - Spherical microporous reservoir-type microcapsules, fabricated using a W/O/W
      double emulsion technique with solvent evaporation and composed of 330 kD
      poly(beta-hydroxybutyrate-hydroxyvalerate (P(HB-HV)) (10.8% HV)/20% PCL II
      containing a range of bovine serum albumin (BSA) loadings, were incubated in
      Hank's buffer, pH 7.4, newborn calf serum (NCS), 1.5% pancreatin and synthetic
      gastric juice containing 10% pepsin over 30 days, and their percentage weight
      loss (PWL) and change in ultrastructural morphology monitored by gravimetry and
      stereoscan electron microscopy (SEM), respectively. The greatest percentage
      weight loss from microcapsules was observed after incubation in NCS and decreased
      in the other NCS > pancreatin > synthetic gastric juice > Hank's buffer. Only 5,
      10 and 15% bovine serum albumin (BSA) loaded microcapsules incubated in Hank's
      buffer and synthetic gastric juice showed a significant increase in PWL with
      increasing percentage BSA loading. The overall sequence of changes in structural
      morphology due to biodegradation occurred at different rates in the different
      'physiological' media. An initial increase in micropore diameter was followed by
      the coalescence of microspores to form macroporous pits (Hank's buffer). Further
      biodegradation in NCS, pancreatin and synthetic juice was characterized by
      significant surface and bulk erosion. Only in pancreatin and NCS did
      biodegradation proceed to a loss of spherical shape and partial (pancreatin) and
      almost total (NCS) disruption of microcapsule structure after 30 days.

PMID- 8994073
TI  - Macroaggregated albumin potentiates the hypoglycemic effect of microencapsulated
      islets in the fed state of streptozotocin-induced diabetic mice.
AB  - Prolonged postprandial hyperglycaemia was noted in streptozotocin-induced
      diabetic mice which had been treated intraperitoneally with 2000-3000 alginate
      poly-L-lysine-alginate (A-P-A) microencapsulated rat islets. We hypothesized that
      the persistent postprandial hyperglycaemia was due to shortage of intracapsular
      calcium ion. In order to study the effect of encapsulated macroaggregated albumin
      (MAA) on the function of microencapsulated islets, we coencapsulated MAA and
      islets in A-P-A microcapsules which we implanted intraperitoneally into
      streptozotocin-induced diabetic mice. From binding study and Scatchard analysis,
      we found that MAA-containing A-P-A microcapsules had a lower calcium binding
      affinity 5.24 +/- 1.20 mM versus 2.35 +/- 0.86 mM, n = 12, p < 0.01) and a higher
      calcium binding capacity (14.34 +/- 1.22 micrograms/mg versus 7.24 +/- 0.82
      micrograms/mg, n = 12, p < 0.01) than empty A-P-A microcapsules. After
      intraperitoneal transplantation of 2000-3000 microcapsules containing islets and
      encapsulated MAA, the basal and postprandial blood glucose levels of the treated
      diabetic mice were not significantly different from that of normal mice. The
      improvement of persistent postprandial hyperglycaemia in these treated diabetic
      mice was not due to the difference of food intake in amount. In conclusion, A-P-A
      microcapsules containing islets and encapsulated MAA functioned better than
      microcapsules containing islets alone in treating streptozotocin-induced diabetic
      mice. The former preparation restored both fasting and postprandial
      hyperglycaemia and put these treated diabetic mice into a cured status of
      diabetes.

PMID- 8994075
TI  - Prolonged retention of cross-linked trypsin in calcium alginate microspheres.
AB  - Trypsin microencapsulated in a calcium alginate matrix was lost quickly through
      diffusion when the microspheres were placed in an aqueous medium. This problem
      was overcome by first reacting trypsin with glutaraldehyde to form cross-linkages
      and then incorporating the enzyme in the alginate microspheres. The performance
      of the cross-linked trypsin remained optimal at pH 8 while it was found to be
      more heat-stable and remained highly active even at 80 degrees C. Esters and
      amides of L-arginine were preferentially hydrolysed by the enzyme indicating that
      cross-linking did not adversely affect the conformation of the active site. There
      was a suppression in enzymatic activity when the microspheres were placed in
      reaction media with an increasing concentration of organic solvent such as
      ethanol, acetonitrile or isopropanol. However, when returned to a totally aqueous
      environment, the enzyme resumed its initial tryptic capability. Such a
      microencapsulated form of cross-linked enzyme may find application in enzyme
      replacement therapy, optical resolution of racemic compounds as well as organic
      synthesis in an aqueous-organic environment.

PMID- 8994076
TI  - In vitro analysis of the release of incorporated agents from sodium caseinate
      microspheres.
AB  - Drug loaded microspheres were successfully prepared using the dairy protein,
      sodium caseinate (SC), as the carrier material and containing
      hydrochlorothiazide, eosin, patent blue violet and sodium salicylate. The
      morphology of the microspheres varied depending on the incorporated material.
      Release of the incorporated agents from these systems was rapid with over 90%
      release in each case within 1 h. Further drug release occurred at a greatly
      reduced rate with a certain proportion of the drug loading appearing to be
      indefinitely entrapped within some of the microspheres. The drug release profiles
      were poorly described using the square root of time and Sinclair and Peppas
      equations but were well described by a biexponential equation. Analysis of the
      parameter estimates from the biexponential equation indicated that the initial
      rapid release phase was essentially completed within 5 min for all but the eosin
      microsphere systems and this timeframe was of the same order of magnitude as that
      found for the initial swelling of these microsphere systems as analysed by
      swelling studies using optical microscopy. Considering both the swelling study
      and the results from the release experiments, it seems likely that addition of SC
      microspheres to aqueous media results in immediate hydration and swelling. This
      process facilitates the rapid diffusional passage of water soluble drugs through
      the swollen and hydrated microsphere matrix, with drug release occurring almost
      unhindered unless other factors favour the retention of the incorporated agent
      with the microsphere.

PMID- 8994077
TI  - Preparation of influenza virosome vaccine with muramyldipeptide derivative B30
      MDP.
AB  - An influenza virosome vaccine, consisting of influenza hemagglutinin
      neuraminidase antigens (HANA), the muramyldipeptide derivative 6-O-(2-tetra
      decylhexadecanoyl)-N-acetyl-muramyl-L-alanyl-D-isoglu tamine (B30-MDP) and
      cholesterol, was prepared by the detergent removal method using a flow-through
      dialyzer, Liposomat. The shape of the influenza virosome vaccine mimicked that of
      the influenza virus, namely, B30-MDP/cholesterol vesicle covered with HANA
      spikes. THe particle size and size distribution of prepared virosomes were
      evaluated by quasi-elastic laser light scattering and gel permeation
      chromatography. The state of incorporation of HANA spikes at the membrane surface
      of virosome was confirmed by electron microscopy. The results indicated that
      virosome formation was influenced by initial B30-MDP concentration in the mixed
      micellar solution prior to dialysis. It is apparent that the initial
      concentration of B30-MDP, relative to the mixed-micelle-to-virosome transition,
      is an important factor for virosome preparation. Accordingly, the transition was
      evaluated and clarified by the changes in membrane fluidity and particle size
      during the dialysis process. The results indicated that it is important to adjust
      the initial B30-MDP concentration in the mixed micellar solution before dialysis
      so that the concentration for the mixed-micelle-to-vesicle transition coincides
      with that for mixed-micelle-to-rosette-transition appropriate for virosome
      formation.

PMID- 8994078
TI  - Microencapsulation of theophylline using ethylcellulose: in vitro drug release
      and kinetic modelling.
AB  - This study details the process of coating theophylline with ethylcellulose using
      the coacervation technique of microencapsulation. Microencapsulation of
      theophylline not only renders it sustained-release, but also decreases its
      gastric irritation and masks the bitter taste (Lin and Yang 1987). The non
      solvent addition method was chosen through a literature survey to ascertain
      various phases of the coacervate (Robinson 1989, Nixon and Wong 1990). A three
      phase diagram was used to determine the optimum quantity of each component
      required. Steps were then carried out to optimize the production. Drug release
      rates of the prepared microcapsules were determined over 12-h cycles using the
      U.S.P. dissolution apparatus and the results obtained were compared with those of
      Knoll's (Germany) sustained-release theophylline capsules. Significant control
      over the rate of drug released from the developed dosage form was achieved during
      the experiment time (12 h). It is concluded that the method employed in this
      study could be effectively used in the preparation of sustained-release
      theophylline microcapsules capable of releasing their drug content for an
      extended period of time. Kinetic studies suggested that both the prepared
      microcapsules and Knoll's product followed Higuchi's model for drug release.
      Particle size and release data analysis from five consecutive batches prepared in
      the laboratory indicated suitable reproducibility of the coacervation process.

PMID- 8994079
TI  - Determination of the physical state of drug in microcapsule and microsphere
      formulations.
AB  - Tolnaftate microcapsules and microspheres were prepared by gelatin-acacia
      coacervation and emulsion-solvent evaporation methods respectively. The physical
      state of the drug in these formulations was determined by using scanning electron
      microscopy (SEM), X-ray powder diffractometry, and differential scanning
      calorimetry (DSC). High pressure liquid chromatographic (HPLC) method was used
      for stability determination and polymer-drug interactions were evaluated using
      FTIR. The pros and cons of each method, in the assessment of the physical state
      of drug in these formulations, were investigated. SEM was found to be useful in
      obtaining a direct visual evidence of the presence of crystalline drug in the
      microspheres, but not for the microcapsule formulation. The DSC method was used
      to determine the physical state of the drug qualitatively in both these
      formulations. In the case of the microcapsules, accurate quantitation of the
      crystalline drug content by DSC was not possible because of the interference of
      thermal events. Powder X-ray diffractometric method was able to demonstrate the
      presence of crystalline drug and polymorphic changes, if any, in both these
      formulations. HPLC data revealed that the drug was stable in these formulations
      for at least 6 months. The FTIR studies indicated the absence of any drug
      interaction with the polymeric matrix materials, during preparation of these
      dosage forms.

PMID- 8994080
TI  - Effects of ammonium ions on the depolarization-induced and direct activation of
      the contractile apparatus in mechanically skinned fast-twitch skeletal muscle
      fibres of the rat.
AB  - Mechanically skinned fibre preparations from the extensor digitorum longus muscle
      of the rat were used to test whether a rise in myoplasmic [NH+4] in the range 2
      10 mM interferes with the mechanism of excitation-contraction coupling in fast
      twitch mammalian muscle. Under our conditions (pH 7.10, Mg2+ 1 mM, temperature 23
      degrees C), [NH+4] up to 10 mM had little effect on the Ca(+)-activated force and
      on the peak of the t-system depolarization-induced force response. However, the
      duration of the depolarization-induced force response was decreased significantly
      at [NH+4] > or = 2 mM. From these data we conclude that the intracellular
      accumulation of NH+4 is not likely to play a major role in fatigue. Nevertheless,
      the build up of NH+4 during fatigue, may have a significant inhibitory effect on
      the force output by decreasing the duration of the t-system depolarization
      induced activation of the contractile apparatus.

PMID- 8994081
TI  - X-ray diffraction studies on thermally induced tension generation in rigor
      muscle.
AB  - Muscle fibres in the rigor state and free of nucleotide contract if heated above
      their physiological working temperature. Kinetic studies on the mechanism of this
      process, termed rigor contraction, indicate that it has a number of features in
      common with the contraction of maximally Ca2+ activated fibres. De novo tension
      generation appears to be associated with a single, tension sensitive, endothermic
      step in both systems. Rigor contraction differs in that steps associated with
      crossbridge attachment and detachment are absent. We investigated structural
      changes associated with rigor contraction using X-ray diffraction. Overall
      changes in the low angle X-ray diffraction pattern were surveyed using a two
      dimensional image plate. Reversible changes in the diffraction pattern included a
      28% decrease in intensity of the 14.5 nm meridional reflection, a 12% increase in
      intensity of 5.9 nm actin layer-line and a somewhat variable 34% increase in
      intensity of 5.1 nm actin layer-line in laser temperature-jump experiments. When
      fibres were heated with a temperature ramp, we found that a 70% decrease in
      intensity of the myosin-related meridional reflection at (14.5 nm)-1 correlated
      with tension generation. A similar decrease in intensity of the 14.5 nm
      reflection is seen during tension recovery following a step change in the length
      of maximally Ca2+ activated fibres. Signals both from actin and actin-bound
      myosin heads contribute to the 5.1 and 5.9 nm actin layer-lines. Our observed
      changes in intensity are interpreted as contraction-associated changes in
      crossbridge shape and/or position on actin.

PMID- 8994082
TI  - Effects of hydrostatic pressure on fatiguing frog muscle fibres.
AB  - Effects of increased hydrostatic pressure (range 0.1-10 MPa) on isometric twitch
      and tetanic contractions of single, intact, frog muscle fibres were examined at
      4, 11 and 21 degrees C and at different stages of fatigue. Twitch tension was
      potentiated by pressure at all temperatures, but the extent of potentiation was
      more pronounced at higher temperatures (34% MPa-1 at 21 degrees C, compared to 8%
      MPa-1 at 4 degrees C). Tetanic tension was depressed by pressure at 4 degrees C
      (approximately 0.7% MPa-1) but was potentiated by pressure at 21 degrees C
      (approximately 0.4% MPa-1). The effect of hydrostatic pressure on the tetanic
      tension was dependent on the fatigue status of the muscle fibre: during the early
      stages of fatigue (when tetanic tension was depressed by < 20%), high pressure
      produced a tension depression (as in an unfatigued muscle fibre), whilst during
      the later stages of fatigue high pressure induced a significant potentiation of
      tetanic. Our results support the suggestion that excitation-contraction coupling
      and contractile activation are impaired during late fatigue. Pressure-effects
      were basically similar to caffeine-effects under a variety of conditions,
      suggesting that an enhancement of Ca2+ release may be contributory to
      potentiation of twitch tension and, in severely, fatigued muscle, potentiation of
      tetanic tension. In the rested state and during early fatigue the main effect of
      pressure is an inhibition of the crossbridge cycle.

PMID- 8994083
TI  - Modification of the bi-directional sliding movement of actin filaments along
      native thick filaments isolated from a clam.
AB  - The properties of bi-directional sliding of F-actin prepared from rabbit skeletal
      muscle moving along clam thick filaments have been characterized in the presence
      of agents known to modify unloaded shortening velocity in muscle to determine if
      the sliding characteristics of actin are similar in the two directions of
      movement. Actin filaments moved at a fast velocity towards the central bare zone
      (11.1 +/- 0.2 microns s-1) and at a slower velocity away from the bare zone (3.9
      +/- 0.3 microns s-1). Movement of filaments at the slow sliding velocity is
      thought to be sustained by a change in orientation of the myosin head. The
      Michaelis Menten constant (Km values) of approximately 0.3 mM in the presence of
      MgATP concentrations of 0.01-2.0 mM at an ionic strength of 43.5 mM were reduced
      to approximately 0.1 mM at low ionic strength (18.5 mM) although the Km values at
      the fast and slow sliding velocities at each ionic strength were similar. In the
      presence of constant concentrations of MgATP, increasing the MgADP concentrations
      from 0.5 to 2mM, decreased the bi-directional sliding velocity of actin. The data
      were well fitted with an equation described by Michaelis Menten kinetics yielding
      mean absolute Km and Ki values of 0.41 +/- 0.01 and 0.44 +/- 0.05 mM for the fast
      velocity and 0.29 +/- 0.07 and 0.45 +/- 0.02 mM for the slow velocity of sliding,
      respectively. The Km and Ki values were not significantly different from each
      other at either the fast or slow sliding velocities. The actin filament sliding
      velocity appeared to be controlled through the thick filament as actin was devoid
      of regulatory proteins and the presence of Ca2+ modified the MgATP dependent
      movement of actin. The pCa value for half maximal sliding velocity was 7.0 for
      both fast and slow velocities. The Km and Ki values and the Ca2+ sensitivity of
      the actin movement at the fast and slow sliding velocity are similar suggesting
      that no major biochemical changes have occurred in the myosin head as a result of
      a change in orientation.

PMID- 8994084
TI  - Concentration-dependent effects of tetracaine on excitation-contraction coupling
      in frog skeletal muscle fibres.
AB  - The effects of low (10-100 microM) concentrations of tetracaine on intermembrane
      charge movement and on the rate of calcium release (Rrel) from the sarcoplasmic
      reticulum (SR) were studied in cut skeletal muscle fibres of the frog using the
      voltage clamp technique. The fibres were mounted in a single or double vaseline
      gap chamber to study the events near the contraction threshold or in a wide
      membrane potential range. Although the 'hump' component of charge movement (Q
      gamma) was suppressed to some extent, the voltage dependence and the parameters
      of the Boltzmann distribution were not modified significantly at tetracaine
      concentrations below 50 microM. At 50 and 100 microM of tetracaine the midpoint
      voltage of the Boltzmann distribution was shifted to higher membrane potentials
      and the steepness was decreased. The total available charge remained the same at
      all concentrations tested. Using fura-2 to measure calcium transients at 100
      microM tetracaine the threshold for calcium release was found to be significantly
      shifted to more positive membrane potentials. Tetracaine reversibly suppressed
      both the early inactivating peak and the steady-level of Rrel but the
      concentration dependence of the effects was markedly different. The inactivation
      component of calcium release was decreased with a Hill coefficient of
      approximately 1 and half effective concentration of 11.8 microM while the steady
      level was decreased with a Hill coefficient of greater than 2 and a half
      effective concentration of 47.0 microM. These results favour two sites of action
      where tetracaine would suppress the calcium release from the SR.

PMID- 8994085
TI  - Myosin isoform transitions in four rabbit muscles during postnatal growth.
AB  - Four rabbit muscles (i.e. semimembranosus proprius, psoas major, biceps femoris
      and longissimus lumborum), differing in their fibre type composition in the
      adult, were investigated during postnatal development. Muscle samples were taken
      at 1, 7, 14, 21, 28, 35, 49 and 77 days of age. Complementary techniques were
      used to characterize myosin heavy chain (MHC) isoform transitions, i.e. SDS-PAGE,
      immunocytochemistry and conventional histochemistry. Good accordance was found
      between electrophoretic and immunocytochemical techniques. Our results show that
      rabbit muscles were phenotypically immature at birth. At 1 day of age, perinatal
      isoform represented 70-90% of the total isoform content of the muscles. Two
      generations of myofibres could be observed on the basis of their morphology and
      reaction to specific antibodies. In all muscles, primary fibres expressed slow
      MHC. In contrast, secondary generation of fibres never expressed slow MHC in
      future fast muscles, while half of them expressed slow MHC in the future slow
      twitch muscle, the semimembranosus proprius. During the postnatal period, all
      muscles displayed a transition from embryonic to perinatal MHC isoforms, followed
      by a transition from perinatal to adult MHC isoforms. These transitions occured
      mainly during the first postnatal month. The embryonic isoform was no longer
      expressed after 14 days, except in longissimus where it disappeared after 28
      days. On the contrary, large differences were found in the timing of
      disappearance of the perinatal isoform between the four muscles. The perinatal
      isoform disappeared between 28 and 35 days in semimembranosus proprius and 35 and
      49 days in psoas and biceps femoris. Interestingly, the perinatal isoform was
      still present in 6% of the fibres in longissimus at 77 days, the commercial
      slaughter age, denoting a great delay in the maturation. Fate of each generation
      of fibres differed between muscles.

PMID- 8994086
TI  - A novel stopped-flow method for measuring the affinity of actin for myosin head
      fragments using microgram quantities of protein.
AB  - The dissociation constant for actin binding to myosin and its subfragments (S1 &
      HMM) is <<1 microM at physiological ionic strength. Many of the methods used to
      measure such affinities are unreliable for a Kd below 0.1 microM. We show here
      that the use of phalloidin to stablise F-actin and fluorescently labelled
      proteins allows the affinity of actin for myosin S1 to be measured in a simple
      transient kinetic assay. The method can be used for Kd's as low as 10 nM and we
      demonstrate that the Kd's can be estimated using only microgram quantities of
      material. Furthermore we suggest how this method may be adapted for ng quantities
      of protein. This will allow the affinity of actin for myosin fragments to be
      estimated for proteins which are difficult to obtain in large quantities i.e.
      from biopsy material or from proteins expressed in baculovirus.

PMID- 8994087
TI  - 37th annual Drosophila Research Conference. San Diego, California 27 April-1 May
      1996.

PMID- 8994098
TI  - Expression of tumor necrosis factor-alpha and transforming growth factor-beta 1
      in cerebrospinal fluid cells in meningitis.
AB  - Meningitis is an acute inflammatory disease of the pia and arachnoid and the
      fluid in the subarachnoid space, in which a participation of cytokines can be
      expected. While tumor necrosis factor-alpha (TNF alpha) promotes inflammatory
      reactions, transforming growth factor-beta 1 (TGF beta 1) has antagonistic
      effects and suppresses the inflammation in the subarachnoid space. We
      investigated the protein concentration and mRNA expression of TNF alpha and TGF
      beta 1 in cerebrospinal fluid (CSF) by ELISA and intracellularly by non
      radioactive in situ hybridization in 23 patients with bacterial or viral
      meningitis. A higher amount of both cytokines on protein and mRNA level,
      especially of TNF alpha, could be detected in bacterial infection. While an
      imbalance of both cytokines with a preponderance of TNF alpha- compared to TGF
      beta 1-mRNA was visible in CSF cells of patients with bacterial meningitis, a
      balance of TNF alpha- and TGF beta 1-mRNA or a higher expression of TGF beta 1
      mRNA could be detected in viral meningitis. In the acute phase of the disease
      neutrophil granulocytes expressed more TNF alpha- and TGF beta 1-mRNA than
      lymphocytes and monocytes/macrophages, while these cell types were dominating the
      cytokine synthesis during the healing phase. These data indicate that
      immunomodulatory mechanisms take place in the CSF compartment itself, regulated
      by CSF cells in different but specific ways. In addition, TGF beta 1 seems to be
      involved in the down-regulation of the inflammatory activity and to be one factor
      in the cytokine network, which could contribute to a lower rate of complications
      and positive outcomes. Moreover this study favors the possibility to monitor the
      immunomodulatory mechanisms by non-radioactive in situ hybridization.

PMID- 8994099
TI  - Enzyme-histochemical and morphological characteristics of fast- and slow-twitch
      skeletal muscle after brain infarction in the rat.
AB  - The right middle cerebral artery was permanently occluded in 12-week-old male
      spontaneously hypertensive rats. After the surgery the rats were subjected to
      repeated behavioural tests during the observation period. Fourteen weeks after
      surgery the fast-twitch extensor digitorum longus (EDL) and the slow-twitch
      soleus muscle of both sides were removed and examined with regard to muscle fibre
      characteristics obtained by histochemical and morphometrical methods. Comparisons
      were made with age-matched controls. Limb placement and the ability to traverse a
      beam or a rotating pole were repeatedly tested 2-13 weeks after the operation. In
      spite of permanent sensorimotor deficits in limb placement and when traversing a
      rotating pole or beam, no increase in pathological changes was noted in either
      EDL or soleus. The number and proportion of fibre types remained unchanged in
      both muscles. There was no difference in muscle fibre size in either EDL or
      soleus. It is concluded that brain infarction in the rat, although causing marked
      impairment of contralateral motor function, does not have a major influence on
      the muscle-fibre morphology or fibre-type composition, irrespective of muscle
      type.

PMID- 8994100
TI  - Absence of neuronal and glial proteins in human and rat leptomeninges in situ.
AB  - Human leptomeningeal (arachnoid and pia mater) cells in culture have been
      demonstrated in replicated studies to express typical neuronal proteins such as
      neurofilament protein and neuron-specific enolase. In addition, they can express
      glial fibrillary acidic protein. The present study examines the possibility that
      neuronal and glial proteins might be present in rat and human leptomeningeal
      cells in situ. The neuronal proteins 160 kDa and 200 kDa neurofilaments, neuron
      specific enolase and microtubule-associated protein 2 were, however, not
      immunolocalized in either the pia mater or arachnoid. Glial fibrillary acidic
      protein and galactocerebroside were also not detected, while fibronectin and
      vimentin immunoreactivities were robust in all layers of the leptomeninges.
      Together with the previously reported expression of some neuronal and astroglial
      markers in cultured human leptomeninges, these observations suggest that culture
      alters the properties of leptomeningeal cells.

PMID- 8994101
TI  - Acoustic neuroma: correlations between morphology and otoneurological
      manifestations.
AB  - Forty-two patients with acoustic neuroma (AN) were studied to determine whether
      different types of neuroma could be correlated with specific signs and symptoms
      of the disease. Based on gadolinium-enhanced TI-weighted MRI sequences, the 42
      cases of AN could be divided into three groups, either by size (small: 11.9%,
      medium: 50%, and large: 38.1%) or by site of origin of the tumour (lateral:
      16.7%, intermediate: 69%, and medial: 14.3%). Relations were found between the
      size and the site of origin of the neuromas and certain clinical, audiological
      and vestibular findings. The clinical presentation seemed to vary with the site
      of origin and the size of the tumour: patients with lateral neuromas generally
      had small tumours, sometimes only located in the internal auditory canal (IAC),
      and presented early subjective hearing loss while patients with medial neuromas
      had larger tumours which grew without causing significant audiological symptoms.
      Normal hearing function was seen only in the patients with medial ANs; however, a
      significant relation between the size or the site of origin of the AN and the
      average hearing threshold was not demonstrated. The sensitivity of the stapedial
      reflex test (SR) was higher for lateral ANs. Anomalies in the brainstem auditory
      evoked potentials (BAEPs) did not seem to be related to either the size or the
      site of origin of the AN. The vestibular tests demonstrated a higher frequency of
      central vestibular involvement in the large tumours, while normal function was
      more frequent in the lateral tumours. In the group studied the combination of
      BAEPs and vestibular tests allowed us to identify all the ANs with an optimal
      level of sensitivity.

PMID- 8994102
TI  - Cerebellar induced aphasia: case report of cerebellar induced prefrontal aphasic
      language phenomena supported by SPECT findings.
AB  - A 73-year-old right-handed man with ischemic infarction in the vascular territory
      of the right arteria cerebellaris superior is described. In the acute phase he
      presented with cerebellar and brainstem symptoms, followed within a few days by a
      paresis of the right arm and unexpected language disturbances of aphasic origin.
      The core features of the aphasic syndrome corresponded to a diagnosis of Luria's
      dynamic aphasia, complicated by expressive and receptive agrammatism. During one
      year follow-up the ataxia and paretic symptoms disappeared but the slightly
      ameliorated aphasic syndrome and the sensory disturbances in the left hemicorpus
      persisted. In the absence of any neuroradiological evidence for a structural
      lesion in the left frontal language areas, the hypothetical causative role of the
      right cerebellar lesion on the contralateral prefrontal aphasic symptomatology is
      advocated and supported by positive 99mTc-hexamethylpropyleneamine oxime single
      photon emission-computed tomography findings, revealing a focal hypoperfusion in
      the clinically suspected areas. In our case, this phenomenon of so-called
      'crossed cerebello-cerebral diaschisis', reflecting the distant functional impact
      of the right cerebellum on the contralateral prefrontal cortical areas, is for
      the first time associated with an aphasiologic substrate. The co-occurrence of a
      right cerebellar lesion and an aphasic syndrome forms the first clinical
      illustration of the pathophysiological hypothesis of a deactivation of prefrontal
      left hemisphere language functions due to the loss of excitatory impulses through
      cerebello-ponto-thalamo-cortical pathways.

PMID- 8994103
TI  - Slowly progressive anarthria with late anterior opercular syndrome: a variant
      form of frontal cortical atrophy syndromes.
AB  - We describe eight patients with slowly progressive speech production deficit
      combining speech apraxia, dysarthria, dysprosody and orofacial apraxia, and
      initially no other deficit in other language and non-language neuropsychological
      domains. Long-term follow-up (6-10 years) in 4 cases showed an evolution to
      muteness, bilateral suprabulbar paresis with automatic-voluntary dissociation and
      frontal lobe cognitive slowing without generalised intellectual deterioration.
      Most disabled patients presented with an anterior opercular syndrome (Foix
      Chavany-Marie syndrome), and pyramidal or extrapyramidal signs. CT and MRI
      findings disclosed asymmetric (left > right) progressive cortical atrophy of the
      frontal lobes predominating in the posterior inferior frontal region, notably the
      operculum. SPECT and PET revealed a decreased cerebral blood flow and metabolism,
      prominent in the left posterior-inferior frontal gyrus and premotor cortex,
      extending bilaterally in the most advanced cases. Pathological study of two cases
      showed non-specific neuronal loss, gliosis, and spongiosis of superficial
      cortical layers, mainly confined to the frontal lobes, with no significant
      abnormalities in the basal ganglia, thalamus, cerebellum, brain stem (except
      severe neuronal loss in the substantia nigra in one case), and spinal cord. We
      propose to call this peculiar syndrome Slowly Progressive Anarthria (SPA), based
      on its specific clinical presentation, and its metabolic and pathological
      correlates. SPA represents another clinical expression of focal cortical
      degeneration syndromes, that may overlap with other similar syndromes, specially
      primary progressive aphasia and the various frontal lobe dementias.

PMID- 8994104
TI  - Cardiac involvement in facio-scapulo-humeral muscular dystrophy: a family study
      using Thallium-201 single-photon-emission-computed tomography.
AB  - Fifteen persons from two consecutive generations of one family affected with
      facio-scapulo-humeral muscular dystrophy (FSHD) were clinically and
      neurophysiologically examined. Diagnostic muscle biopsies were obtained from two
      members. Linkage analysis showed that all four affected members of the family
      inherit the same 4q35 haplotype giving a lod score of z = +1.44. Six family
      members were examined by ECG at rest and under stress, by two-dimensional
      echocardiography, and by cardiac Thallium-201 single-photon-emission computed
      tomography (Tl-201-SPECT) under dobutamine stress and at rest. Abnormal reduced
      Tl-201 uptake in cardiac SPECT was only found in the affected members of the
      family. Therefore we suggest that cardiac Tl-201-SPECT abnormalities in FSHD
      reflect cardiomyogenic changes in this type of muscular disease.

PMID- 8994105
TI  - Local cerebral blood flow in motor neuron disease: correlation with clinical
      findings.
AB  - Local cerebral blood flow (CBF) measured by xenon-enhanced CT was correlated with
      the clinical findings in 21 patients with motor neuron disease (mean +/- SD age,
      60 +/- 10 years). In 11 patients, CBF was also measured after intravenous
      injection of 2 mg thyrotropin releasing hormone (TRH). There were no significant
      differences in CBF of the cerebral cortex, basal ganglia, thalamus, and
      subcortical white matter with respect to age, duration of illness, or presence (n
      = 9) or absence (n = 12) of bulbar palsy. In patients with upper motor neuron
      disturbance (n = 10), however, local CBF in the frontal cortex was significantly
      lower (p < 0.05) than in those without it (n = 11). Within the frontal cortex,
      CBF reduction was marked in the upper posterolateral part (p < 0.05) that
      included the motor and premotor areas. Intravenous administration of TRH did not
      significantly alter the local CBF in any of the brain regions examined. An
      additional patient with motor neuron disease and severe dementia showed marked
      CBF reduction in the frontal lobe, which was in common with but much greater than
      the reduction in those exhibiting subcortical dementia (e.g., progressive
      supranuclear palsy). We conclude that in motor neuron disease patients with upper
      motor neuron involvement, the selective reduction of CBF in brain regions that
      include primary motor and premotor areas may reflect functional disturbance or
      neuronal degeneration in these regions. The ameliorating effect of TRH in
      patients with motor neuron disease, if any, appears not to be related to
      increases in local CBF or activation of brain function.

PMID- 8994106
TI  - Brain 6-[18F]fluorodopa metabolism in early and late onset of Parkinson's disease
      studied by positron emission tomography.
AB  - We measured 6-[18F]fluorodopa (FDOPA) uptake in the caudate nucleus and the
      putamen of 20 patients with early and late onset of Parkinson's disease (EOPD and
      LOPD) and 20 normal control subjects using positron emission tomography. The mean
      influx rate constant values (Ki) were significantly reduced in the caudate
      nucleus and the putamen of the patients with EOPD and LOPD compared with age
      matched control groups (p < 0.01), respectively. There were significant negative
      correlations between Ki values in the caudate nucleus (r = -0.67, p = 0.0024) and
      the putamen (r = -0.67, p = 0.0014), and duration of disease in the LOPD group
      compared with the EOPD group. Similar negative relationships between Ki values
      and clinical stages by Hoehn and Yahr and degrees of main clinical symptoms
      (bradykinesia, tremor and rigidity) were more markedly seen in the LOPD group
      than in the EOPD group. The present results suggest that the function of
      presynaptic dopaminergic terminals correlates well with clinical disease severity
      and degrees of main symptoms in the LOPD group, but not in the EOPD group. We
      speculate that compensatory up-regulatory function in the postsynaptic
      dopaminergic receptors may modify disease severity and the degrees of main
      clinical symptoms of EOPD.

PMID- 8994107
TI  - Glucose metabolism in the cortical and subcortical brain structures in multiple
      system atrophy and Parkinson's disease: a positron emission tomographic study.
AB  - The brain glucose metabolism was studied by PET with 18F-FDG in 11 patients with
      multiple system atrophy (MSA) and 12 patients with idiopathic Parkinson's disease
      (PD). Seven of the 11 MSA patients were diagnosed as having olivopontocerebellar
      atrophy, two had striatonigral degeneration, while two demonstrated Shy-Drager
      syndrome. The glucose metabolic rates for each region in the PD patients showed
      no difference from the normal controls. The frontal, temporal and parietal
      cortical glucose metabolic rates and the caudate, the putaminal, the cerebellar
      and the brainstem glucose metabolic rates in the MSA patients decreased
      significantly from the controls. The atrophy of the cerebellum and the brainstem
      in the MSA patients were scored by MRI. The cerebellar and brainstem glucose
      metabolism in the MSA patients decreased as the atrophy score in such regions
      advanced in each group; however, some patients with no atrophy showed a decreased
      glucose metabolism. Although the cerebellar and the brainstem glucose metabolism
      decreased in all MSA patients, such a decrease was not observed in the SND
      patients. The decrease in the glucose metabolism for the non-cortical regions in
      the MSA patients seems to be due to a diffuse depletion of the neurons not
      restricted to the nigrostriatal neurons. Deafferentation to the cerebral cortices
      seems to result in a decreased cortical metabolism. The differences in the
      glucose metabolism between MSA and PD as assessed by PET may be caused by the
      pathophysiological differences between MSA and PD, and such differences therefore
      appear to be useful when making a differential diagnosis between MSA and PD. The
      relative sparing of the brainstem and cerebellar glucose metabolism is considered
      to be a feature of patients with SND.

PMID- 8994108
TI  - Nimodipine improves brain energy metabolism and blood rheology during ischemia
      and reperfusion in the gerbil brain.
AB  - Whether nimodipine improves cerebral blood flow (CBF) and metabolism in cerebral
      ischemia remains a controversial issue. We investigated the effect of nimodipine
      on CBF, brain energy metabolism, using a laser-Doppler flowmeter and in vivo
      31phosphorus nuclear magnetic resonance (31P NMR) spectroscopy, and blood
      rheology during forebrain ischemia and reperfusion in gerbils. Eighty-three adult
      gerbils received nimodipine (1 micrograms/kg/min), or an equal volume of the
      vehicle, or saline, over 60 min prior to a transient forebrain ischemia for 60
      min. We measured sequential changes in phosphocreatine (PCr) / inorganic
      phosphate (Pi) ratio, beta-ATP/Pi ratio, and intracellular pH (pHi) during
      ischemia and reperfusion by 31P NMR spectroscopy, and the measurement of whole
      blood viscosity (WBV) at 60 min after reperfusion. CBF was measured continuously
      throughout the study by a laser-Doppler flowmeter. During forebrain ischemia,
      PCr/Pi and beta-ATP/Pi ratios were higher significantly in the nimodipine-treated
      group (p < 0.05 and 0.01) than in the vehicle- or saline-treated groups. During
      reperfusion, PCr/Pi and beta-ATP/Pi ratios recovered significantly only in the
      nimodipine-treated group (p < 0.05 and 0.01). The WBV at high shear rate (562.5 s
      1) lowered significantly in the nimodipine-treated group (p < 0.05) compared with
      the vehicle- or saline-treated group. CBF was higher significantly only during
      administration of nimodipine in the nimodipine-treated group (p < 0.01) than
      other groups. Nimodipine improved brain energy metabolism and blood rheology
      during forebrain ischemia and reperfusion in the gerbil brain.

PMID- 8994109
TI  - Muscle morphology and mitochondrial investigations of a family with autosomal
      dominant cerebellar ataxia and retinal degeneration mapped to chromosome 3p12
      p21.1.
AB  - The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative
      disorders with ataxia and dysarthria as early and dominant signs. In ADCA type
      II, retinal degeneration causes severe visual impairment. ADCA type II has
      recently been mapped to chromosome 3p by three independent groups. In the family
      with ADCA type II studied here, the disease has been mapped to chromosome 3p12
      p21.1. Histochemical examination of muscle biopsies in 5 cases showed slight
      neurogenic atrophy and irregular lobulated appearance or focal decreases of
      enzyme activity when staining for NADH dehydrogenase, succinic dehydrogenase and
      cytochrome oxidase. Ragged-red fibres were scarce. Electron microscopic
      examination showed uneven distribution of mitochondria with large fibre areas
      devoid of mitochondria and/or large subsarcolemmal accumulations of small rounded
      mitochondria, and frequent autophagic vacuoles. These vacuoles contained remnants
      of multiple small rounded organelles, possibly mitochondria, and had a remarkably
      consistent ultrastructural appearance. Biochemical investigation of mitochondrial
      function showed reduced activity of complex IV and slightly reduced activity of
      complex I in the respiratory chain in a severely affected child while no
      abnormalities were found in his affected uncle.

PMID- 8994110
TI  - Low-level EMFs are transduced like other stimuli.
AB  - The aims of this study were to test the theory that transduction of low-level
      electromagnetic fields (EMFs) is mediated like other stimuli, and to determine
      the false-negative rate of the method used to assess the occurrence of
      transduction (intra-subject comparison of stimulus and non-stimulus states
      (ICOS)). A light stimulus was chosen as a basis of comparison because light could
      be applied and removed at precise time points, similar to the manner in which
      EMFs were controlled. Subjects exposed to a weak light stimulus during 2-second
      epochs exhibited alterations in brain electrical activity that were similar to
      those previously observed in subjects exposed to EMFs. The false-negative rate of
      the ICOS method was 61%, since it registered an effect in only 39% of the
      subjects (11/28) whereas all subjects were actually aware of the light. In a
      second group of subjects that were exposed to 0.8 G (1.5 or 10 Hz), 58% (11/19)
      exhibited similar alterations in brain activity, as determined using ICOS.
      Previous measurements in the same subjects using a different method showed that
      the EMFs actually affected brain electrical activity in all subjects;
      consequently, the false-negative rate was 42% when an EMF was used as the
      stimulus. The results suggested that the post-transduction brain electrical
      processes in human subjects were similar in the cases of EMF and light stimuli,
      as hypothesized, and that the high negative rate of the ICOS method (here and in
      previous studies) was composed partly or entirely of false-negative results.

PMID- 8994111
TI  - AIDS dementia complex in the Italian National AIDS Registry: temporal trends
      (1987-93) and differential incidence according to mode of transmission of HIV-1
      infection.
AB  - OBJECTIVES: To investigate the occurrence of AIDS dementia complex (ADC) in Italy
      and its incidence over time, examining possible correlations between this
      condition and some demographic and immunological variables. DESIGN: Inception
      cohort. Data collected from the case notification forms of the Italian National
      AIDS Registry. SUBJECTS: 16813 consecutive AIDS cases reported to the National
      AIDS Registry from August 1, 1987 through October 31, 1993 were included.
      STATISTICAL METHODS: All data refer to the time of AIDS diagnosis as reported on
      the case notification forms. Main analyses of the monthly proportion of ADC cases
      were by multiple logistic regression. RESULTS: 1364 subjects (8.1%) were reported
      with a diagnosis of ADC as the first AIDS defining disease, either as the only
      manifestation or associated with other AIDS defining conditions. At the time of
      AIDS diagnosis, the observed ADC/AIDS proportion was significantly higher among
      intravenous drug users (IVDU), 9.1%, compared to heterosexuals, 6.3%, and homo
      bisexual men, 5.2%. Simple logistic regression analysis showed a significant (p <
      0.0001) quadratic trend in the monthly ADC/AIDS proportion, peaking in March 1990
      and decreasing thereafter. Multiple logistic regression, adjusting for month of
      diagnosis, showed that IVDUs have consistently the highest risk and homo-bisexual
      men the lowest, although differences tended to decrease with increasing age.
      Older age, in fact, was highly associated with an increased risk, especially
      within the homo-bisexual and heterosexual transmission categories. CD4 + cells
      counts proved to have no significant effect on the risk of progressing to AIDS
      with ADC rather than with any other AIDS indicative disease. CONCLUSIONS: ADC is
      a relatively frequent manifestation at diagnosis of AIDS among Italian patients,
      and particularly in IVDUs. Differences in its occurrence were found according to
      time of diagnosis, transmission category and age.

PMID- 8994112
TI  - Transcranial magnetic stimulation of the human frontal eye field.
AB  - The region of cortex over which transcranial magnetic stimulation (TMS) can delay
      saccadic eye movement was investigated. With TMS delivered in the reaction time
      foreperiod of auditory-triggered saccades, saccade onset could be delayed by up
      to 60 ms. The area of cortex over which TMS could delay saccade onset was located
      near the inter-aural line, approximately 6 cm lateral to the vertex, and was
      situated between areas over which TMS could generate motor evoked potentials in
      muscles of the hand and face. It is concluded that this area corresponds to the
      human frontal eye field and is closely associated with the motor strip, at a
      level between the representations of the hand and the face, and that stimulation
      of this region can interfere with the programming and execution of externally
      triggered saccades.

PMID- 8994113
TI  - Autoradiographic distribution of [3H]-(S)-zacopride-labelled 5-HT3 receptors in
      human brain.
AB  - Autoradiographic binding studies using the 5-HT3 (5-hydroxytryptamine3) receptor
      radioligand, [3H]-(S)-zacopride (0.5 nM), identified a heterogeneous distribution
      of specific binding sites (defined by granisetron, 1 microM) throughout the human
      brain. Highest radiolabelled 5-HT3 receptor densities were detected in discrete
      nuclei within the brainstem (nucleus tractus solitarius, area postrema, spinal
      trigeminal nerve nucleus; 50-200 fmol/mg tissue equivalent) with more modest
      levels of expression in the forebrain (e.g. hippocampus, nucleus accumbens,
      putamen, caudate; 4-17 fmol/mg tissue equivalent). Within the hippocampal
      formation, radiolabelled 5-HT3 receptors were differentially distributed with
      highest levels in the granule cell layer of the dentate gyrus. Saturation studies
      with [3H]-(S)-zacopride (0.05-16 nM; non-specific binding defined by granisetron,
      10 microM) binding to homogenates of human putamen indicated that [3H]-(S)
      zacopride (0.05-16 nM; non-specific binding defined by granisetron, 10 microM)
      binding to homogenates of human putamen indicated that [3H]-(S)-zacopride
      labelled an apparently homogenous population of binding sites (Bmax = 72 + 7 fmol
      mg-1 protein, pKd = 8.69 +/- 0.09, Hill coefficient = 0.99 +/- 0.06, mean +/-
      SEM, n = 4). The pharmacological profile of [3H]-(S)-zacopride binding to
      homogenates of putamen indicated the selective labelling of the human variant of
      the 5-HT3 receptor. The marked differences, however, in the pharmacology (e.g.
      low affinity for D-tubocurarine) and relative distribution (e.g. presence of 5
      HT3 receptors in the human extrapyramidal system) of 5-HT3 receptors in the human
      forebrain when compared with other species further necessitates caution in
      predicting clinical responses based on data generated in animal models of
      disease.

PMID- 8994114
TI  - Increased apoptotic response to 2-deoxy-D-ribose in ataxia-telangiectasia.
AB  - Ataxia-telangiectasia (AT) is an autosomal recessive disease characterized by
      neurodegeneration and immunodeficiency. Hypersensitivity to radiation and
      chromosome instability are the biological markers of this disease. The gene
      responsible for AT (ATM), has been identified on chromosome 11q22-23; it encodes
      a large polypeptide partially homologous to the phosphatidylinositol (PI) 3
      kinase family. PI 3-kinase is a protein family playing an important role in the
      prevention of apoptosis. In order to investigate the apoptosis pathway, we tested
      peripheral blood cells from AT patients and controls exposed to 2-deoxy-D-ribose
      (dRib), a reducing sugar that induces apoptosis in human quiescent lymphocytes,
      probably through oxidative damage. Our results show that the response to dRib
      induced apoptosis is significantly more elevated in AT cells than in control
      cells, suggesting that the apoptotic process plays a role in the pathogenesis of
      AT disease.

PMID- 8994115
TI  - Enhanced expression of chemotactic receptors in multiple sclerosis lesions.
AB  - We have previously shown that astrocytes and microglia express the receptors for
      C5a, interleukin-8 (IL-8) and N-formyl-Met-Leu-Phe (FMLP) in vitro. The
      expression and function of chemotactic receptors in the central nervous system
      (CNS) is, however, largely unexplored. In this study, we examined tissue sections
      from normal human brain and active, chronic active and chronic silent multiple
      sclerosis (MS) lesions for the expression of the receptors for C5a, IL-8 and FMLP
      by immunohistochemistry. In normal brain tissue, the expression of all three
      receptors was seen at low levels on astrocytes and microglia. In contrast,
      expression for all three receptors was markedly elevated on foamy macrophages in
      the acute and chronic active MS lesions. In addition, fibrous astrocytes stained
      intensely for the C5a receptor in the chronic active disease. Receptor expression
      in the chronic silent lesion was low and similar to that seen in normal brain,
      with staining confined to a few hypertrophic astrocytes and foamy macrophages.
      These are the first studies to demonstrate expression of these receptors in the
      CNS and elevated receptor expression in inflammatory MS lesions. The data suggest
      that these chemotactic receptors may play a role in inflammatory responses in MS
      and possibly in other CNS diseases.

PMID- 8994116
TI  - Predictors of stroke pattern in hypertensive patients.
AB  - BACKGROUND AND PURPOSE: Hypertension is a recognized risk factor for stroke.
      However, it is not clear why hypertensive patients may have different types and
      causes of stroke. METHODS: The possible role of coexisting factors was studied in
      1057 patients with hypertension and first stroke admitted to a population-based
      stroke center. We used logistic regression analysis (multivariate and
      polychotomous) and the Lausanne Stroke Registry definitions of cerebral
      hemorrhage, cerebral infarction, lacunar infarction, cardioembolism and large
      artery disease. RESULTS: Cerebral hemorrhage was not more frequent in these
      hypertensive patients (111/1057 = 10.5%) than in the total population of the
      registry (213/2145 = 10%). Cerebral infarction was associated with age above the
      median (69 years), diabetes, smoking history, family history of cardiac or
      cerebrovascular disease, hypercholesterolemia and previous TIA. In the ischemic
      group (n = 946), patients suffered from a lacunar infarction in 36% of the cases,
      large artery disease was present in 21% of them and cardioembolism in 14.5%.
      Large artery disease correlated with smoking history (odds ratio: 2.14; 95%
      confidence intervals: 1.55-2.95) and previous TIA (OR:1.96; 95% CI:1.39-2.75).
      Cardioembolism correlated with age over 69 years (OR:2.13; 95% CI:1.47-3.09). In
      patients with previous TIA and smoking history, large artery disease was presumed
      in 45% of the cases (vs 21%). Patients aged over 69, suffered a cardioembolic
      stroke in 29% of the cases (vs 14.5%). Lacunar infarction occurred in 49% of
      patients aged less than 70 years when no history of smoking or previous TIA was
      present (vs 36%). CONCLUSION: The associations between hypertension, TIA, age and
      smoking history may partially explain why patients with hypertension are more
      likely to develop a cerebral hemorrhage, lacunar infarction, cardioembolic or a
      large artery disease stroke.

PMID- 8994117
TI  - The recovery of long-term denervated rat muscles after Marcaine treatment and
      grafting.
AB  - Disruption of the nerve supply results in the rapid loss of mass and contractile
      force in skeletal muscles. These losses are reversible to a high degree in short
      term denervated muscles with grafting and nerve implantation. However, return is
      much poorer in long-term denervated muscles. This study examined the basis for
      the differences in the recovery of non-denervated and 7-month denervated rat
      extensor digitorum longus (EDL) muscles after grafting and nerve implantation. We
      found that the level of recovery is related to the ability of muscle fibers to
      degenerate and regenerate after grafting. Fibers within long-term denervated
      muscles do not degenerate and regenerate as well as those within muscles which
      are not denervated prior to grafting. The functional recovery of the denervated
      muscles is significantly improved when their fibers are induced to degenerate
      with the myotoxic anesthetic, Marcaine, Degeneration of these fibers is followed
      by massive regeneration. The finding that denervated muscles are capable of being
      restored to a significant level by inducing regeneration may be useful in the
      clinical treatment of denervated muscles.

PMID- 8994118
TI  - Quantitative study of intermediolateral column cell counts in Machado-Joseph
      disease.
AB  - The number of intermediolateral column (ILC) neurons in 6 alternating segments
      from the 2nd to 12th thoracic segment of the spinal cord were studied in 4 cases
      with Machado-Joseph disease (MJD), 3 cases with olivopontocerebellar atrophy
      (OPCA), a case with Shy-Drager syndrome (SDS), and 5 normal controls. We counted
      the number of ILC neurons with clearly defined nucleoli in 12 sections of each
      segment, each section 20 microns thick and taken at 100 microns intervals and
      then divided the 6 alternating segments into 3 groups, upper (Th2, 4), middle
      (Th6, 8) and lower (Th10, 12). In each of the three groups of normal control
      cases, the number of ILC neurons had decreased with aging. In all MJD cases, the
      number of ILC neurons had moderately decreased in comparison with age-matched
      controls. One of the MJD cases showed a marked decrease in the number of ILC
      neurons, as did the SDS case. The ILCs of the entire thoracic spinal cord in the
      MJD cases were moderately involved.

PMID- 8994119
TI  - Transcallosal inhibition in cortical and subcortical cerebral vascular lesions.
AB  - The excitability of the motor cortex after transcranial magnetic stimulation was
      investigated in 10 patients with purely subcortical, and in 22 patients with
      cortical-subcortical cerebrovascular lesions. In the first investigation we
      applied magnetic double stimuli over both motor cortices with different inter
      stimulus intervals. The first (conditioning) stimulus was applied to the affected
      hemisphere and the second stimulus (test stimulus) to the unaffected side. The
      responses of the first dorsal interosseal (FDI) muscle, contralateral to the test
      stimulus, were recorded after applying the test stimulus alone and at inter
      stimulus intervals of 5 ms, 7 ms, 15 ms, 30 ms and 60 ms. In a second
      investigation the patients were asked to activate their non-paretic first dorsal
      interosseus muscle and the magnetic stimulus was applied over the affected
      hemisphere. The EMG responses were rectified and averaged. Patients with
      subcortical cerebral lesions below the centrum semiovale (i.e., having no effect
      on the transcallosal fibres) displayed a pronounced inhibition of one motor
      cortex after the stimulation of the contralateral side, comparable with normal
      subjects. Patients with cortical-subcortical cerebral lesions displayed only
      partly less inhibition of their motor cortex but the results in this group were
      not uniform. Since inhibition was preserved in patients with subcortical lesions,
      which had destroyed the corticospinal tract, we conclude that this inhibition is
      not mediated through an ipsilateral projection but via a transcallosal route.

PMID- 8994120
TI  - Experimental autoimmune myositis in SJL/J mice produced by immunization with
      syngeneic myosin B fraction. Transfer by both immunoglobulin G and T cells.
AB  - An experimental autoimmune myositis (EAM) was produced by immunizing SJL/J mice
      with the myosin B (MB) fraction of the syngeneic muscle. Immunoblot analysis of
      the IgG of the EAM mice demonstrated antibodies against a variety of muscle
      proteins. The condition was then transferred to normal mice by both injecting
      immunoglobulin G or T cells from the EAM mice. This is the first model of
      transferrable EAM caused by syngeneic muscle fraction, and it has an unique
      resemblance to human inflammatory myopathies involving both humoral and cellular
      immune mechanisms.

PMID- 8994122
TI  - High resolution proton MR spectroscopy of cerebrospinal fluid in MS patients.
      Comparison with biochemical changes in demyelinating plaques.
AB  - Proton magnetic spectroscopy (1H-MRS) investigation was performed on CSF samples
      of patients with neurological inflammatory diseases including 52 cases of
      multiple sclerosis (MS). 12 acute idiopathic polyneuropathies, 20 acute
      meningitides (10 viral and 10 bacterial). Spectra were compared with those
      acquired in 18 neurological controls. High CSF lactate levels were found in MS
      patients during clinical exacerbation of relapsing-remitting course (p = 0.036 vs
      neurological controls). In MS patients with MRI evidence of Gd-enhanced plaques
      CSF lactate was higher than in patients with MRI inactive plaques (p = 0.017).
      CSF lactate positivity correlated with number of CSF mononuclear cells in MS
      patients with clinical activity (p = 0.05) as well as in MS patients with MRI
      enhancement (p = 0.003). A comparative 1H-MRS investigation in vivo on localized
      demyelinating areas confirmed an elevated lactate signal in Gd-enhanced (61%)
      more frequently than in unenhanced (22%) plaques (p = 0.03). MS patients with
      high lactate signal in active plaques showed high lactate levels in CSF.
      Increased CSF lactate was found also in patients with acute meningitis and
      idiopathic polyneuropathy. These data suggest that changes in lactate levels may
      depend on anaerobic glycolytic metabolism in activated leukocytes during
      inflammatory diseases. A decrease of CSF formulate levels was found in MS
      patients during active and inactive clinical phase (p = 0.037, p=0.05 vs
      neurological controls respectively). Formate changes might be related to a
      disorder of choline-glycine cycle in MS. 1H-MRS in vivo showed significant
      increase of choline in acute plaques, whereas a decrease of N-acetyl aspartate
      was found in chronic plaques; these metabolites are undetectable in CSF. CSF
      glucose levels were lower in bacterial than in viral meningitis (p = 0.014) and
      in neurological controls (p = 0.05). These observations suggest that 1H-MRS may
      be able to detect CSF metabolic impairment in neurological inflammatory diseases.
      In MS some CSF findings reflect metabolic changes occurring in brain
      demyelinating areas, and they could be useful foe evaluation of disease activity
      in different stages of disease evolution.

PMID- 8994121
TI  - Central phenotype and related varieties of spinocerebellar ataxia 2 (SCA2): a
      clinical and genetic study with a pedigree in the Japanese.
AB  - The gene for SCA2 has been mapped to chromosome 12q23-q24.1, but the mutant gene
      remained to be identified. When studying a Japanese family with SCA2, we noted
      that clinical features and disability varied among patients, with the central
      feature being progressive ataxia-slow eye movement-hyporeflexia syndrome.
      Additional symptoms were parkinsonism with minor cerebellar deficits, and severe
      ataxia with choreoathetosis. Our experience plus related literature documentation
      indicates that choreoathetosis is not so rare at the advanced stage of the
      disease, with onset at an early age, and that the variety of SCA2 phenotype
      depends on age at onset and duration of the disorder.

PMID- 8994123
TI  - Cerebral blood flow and clinical outcome in patients with thalamic hemorrhages: a
      comparison with putaminal hemorrhages.
AB  - It has been reported that the reduction of cerebral blood flow (CBF) is more
      pronounced with thalamic hemorrhages than with putaminal hemorrhages, and the
      clinical outcome is worse with the former. However, the mechanism underlying
      these differences is not clear. We compared neurologic status, hematoma volumes,
      outcome scores. and early (< 1 month) and late (2-12 month) CBF values between 15
      patients with thalamic hemorrhages and 28 patients with putaminal hemorrhages. We
      also correlated thalamic versus hemispheric CBF on each side and ipsilateral
      versus contralateral thalamic and hemispheric CBF. Finally, we evaluated the
      response to acetazolamide during the late stage. Thalamic hemorrhages were
      associated with a more pronounced reduction in CBF bilaterally, even though their
      hematoma volumes were much smaller. Contralateral to the hemorrhage, the
      discrepancy in CBF values between the two groups became greater in the late stage
      because CBF started to recover in putaminal hemorrhages but persistently
      deteriorated in thalamic hemorrhages. In the group with thalamic hemorrhages, the
      correlation between thalamic and hemispheric CBF ipsilateral to the hemorrhage
      and between thalamic CBF on both sides was disrupted in the early stage and
      restored in the late stage, whereas the correlation between the hemispheric CBF
      values was consistently preserved. Acetazolamide invariably augumented CBF during
      the late stage. The clinical outcome was worse in the thalamic group, but CBF
      values correlated negatively with outcome in both groups. We conclude that the
      reduction of CBF in the late stage may be secondary to metabolic depression due
      to transneural depression ('diaschisis'). The metabolic depression in thalamic
      hemorrhages is more extensive and persistent than in putaminal hemorrhages, which
      probably accounts for both the more pronounced CBF reduction and the worse
      outcome.

PMID- 8994124
TI  - Non-traumatic cerebral hemorrhage in Saudi Arabs: a hospital-based study of 243
      cases.
AB  - This is a retrospective study involving 243 Saudi Arabs with non-traumatic
      cerebral hemorrhages confirmed by CT scan. Intracerebral hemorrhages accounted
      for about 20% of all strokes in this population. THe male to female ratio was
      2.74 which is slightly higher than those reported from elsewhere. Peak frequency
      was around 60 years. Hypertension was the most common cause accounting for 64% of
      the cases, hemopathies/coagulopathies for 10% and arteriovenous malformations
      (AVMs) for 6%. THe cause was undetermined in 21% of patients. Amyloid angiopathy
      was probably underrepresented due to lack of autopsy correlation. The etiologies
      were, however, age-related with a clear predominance of AVMs and coagulation
      disorders before the age of 40 years. Hypertensive hemorrhages were located in
      the putamen in 46% of cases compared to 20% in non-hypertensive patients while
      52% of non-hypertensive hemorrhages were lobar in location compared to 20.5% in
      hypertensives. Early mortality (19%) in our series was relatively low compared to
      reports from the industrialized world.

PMID- 8994125
TI  - Mitochondrial DNA polymorphism in substantia nigra.
AB  - Inefficiencies in mitochondrial respiration mainly affecting complex I and IV
      activities, occur with increasing age and have been suggested as a possible
      etiological factor in age-related neurodegenerative diseases. It has been
      suggested that this finding may be explained by an accumulation of mtDNA
      mutations. We hypothesise that some polymorphic mitochondrial genomes encode less
      efficient respiratory protein subunits and are therefore less tolerant of
      acquired mutations. If this hypothesis is correct, individuals with 'less
      efficient' mtDNA genotypes may be predisposed both to more rapid biological aging
      and to neurodegenerative disease. In this study we investigate the substantia
      nigra mtDNA composition from 4 elderly individuals (2 non-parkinsonian and 2 with
      idiopathic Parkinson's disease) to determine whether there is sufficient
      polymorphism to account for different possible respiratory efficiencies. THe
      mitochondrial tRNAArg, tRNAHis, tRNAScr, tRNALeu(CUN), ND4L, ND4 and ND5 genes as
      well as parts of the ND3 and ND6 subunit coding regions were analysed (4221 bp),
      revealing the presence of multiple deletions and 48 discrete polymorphic sites.
      These included 23 missense, two tRNA and one nonsense polymorphism. Eight of the
      missense polymorphisms caused nonconservative amino acid replacements at sites of
      moderate to high evolutionary constraint. These findings suggest that mtDNA
      diversity in the ageing brain may account for a range of bioenergetic outcomes.
      The variation in mtDNA genotype involves both inherited (fixed familial)
      polymorphism and superimposed acquired mutations.

PMID- 8994127
TI  - Dementia paralytica in a fifteen-year-old boy.
AB  - A 15-year-old boy, whose history revealed an unremarkable pregnancy, birth and
      neonatal period and who had shown a normal motor and mental development,
      presented at the hospital with deterioration of cognitive functions since the age
      of 7. He was bedridden with manifest ataxia involving all limbs, anisocoria and a
      sluggish to absent pupil reaction to light. Syphilis serology was positive with a
      Venereal Disease Research Laboratory (VDRL) titer of 1:256 and a Treponema
      pallidum Haemagglutination Assay (TPHA) titer of 1:163840. Cerebrospinal fluid
      (CSF) protein concentration was 55 mg/dl and CSF-leucocyte count was 14/mm3 (85%
      mononuclear cells). CSF-VDRL-titer was 1:16. A diagnosis of congenitally acquired
      dementia paralytica was made, since the boy's parents' clinical exam and serology
      results were suggestive for latent syphilis. Although cognition was still very
      much deteriorated five months following penicillin treatment, clinical
      examination revealed partial recuperation. Screening for syphilis should be part
      of routine testing in every subject presenting with cognitive deterioration,
      regardless of age.

PMID- 8994126
TI  - Reversal of encephalopathy during treatment with amphotericin-B.
AB  - A case of reversible encephalopathy during treatment with Amphotericin-B (AMB) is
      described. The comparison of the clinical course of AMB encephalopathy with total
      dose of AMB, cranial radiotherapy and MRI data available in previously reported
      cases, shows that this complication is characterized by a progressive, dose
      dependent course, possibly influenced by cranial irradiation.

PMID- 8994128
TI  - Consensus statement on the definition of orthostatic hypotension, pure autonomic
      failure, and multiple system atrophy.

PMID- 8994129
TI  - Exacerbation of myasthenia gravis during interferon-alpha treatment.

PMID- 8994130
TI  - Uniformity of protective antigens among isolates of the cattle tick, Boophilus
      microplus.
AB  - Gut membrane antigens were extracted from ten isolates of the cattle tick
      Boophilus microplus; the antigen extracts were probed with bovine antisera and
      three murine monoclonal antibodies (mAbs) in Western blots and dot-ELISA. The
      antisera had been obtained from cattle which were vaccinated with larval and gut
      extracts of B. microplus, and which were subsequently protected (84% and 94%
      respectively) against challenge with B. microplus. One of the mAbs (QU13) has
      been demonstrated to precipitate protective antigens form the midgut of B.
      microplus. Gut antigens from all ten isolates displayed similar reactivity
      profiles against bovine antisera and also against mAbs in Western blots. The end
      point titres of antigens in dot-ELISA showed four-fold variation between isolates
      against bovine antisera, and also against mAb QU13. Larval membrane antigen
      extracted from N-strain B. microplus reacted with QU13 in dot-ELISA, indicating
      that protective antigens are common to both larval and adult stages of B.
      microplus. It was concluded that protective antigens recognized by QU13 and
      antigens recognized by sera from protected cattle were conserved between the ten
      isolates examined, and between life-cycle stages.

PMID- 8994131
TI  - Phenology of Stomoxyinae in a Kenyan forest.
AB  - The biology of nineteen taxa of African Stomoxyinae was studied during
      experiments with odour-baited Vavoua traps in Nairobi National Park, Kenya. Both
      male and female Stomoxys were captured in similar numbers with CO2 released at 2
      l/min or octenol released at 2 mg/h. Some species of Haematobosca reacted
      synergistically to a combination of these attractants, producing large increases
      in catch. Stygeromyia and Rhinomusca responded only to CO2 and Prostomoxys did
      not respond to either bait. Many different activity patterns were documented in
      these genera, but most activity was concentrated just prior to sunset. For
      example, at peak densities nearly 1500 Stomoxyinae representing fourteen taxa
      were caught in a single trap between 18.00 and 19.00 hours. The Stomoxyinae
      community was exceptionally diverse when compared with other biting fly
      communities. Using data from traps set with different odour baits in the park
      forest, Shannon-Wiener diversity indices (H') varied from 2.5 to 2.8, and
      evenness (J') varied between 0.61 and 0.68. The Stomoxys population was extremely
      female-biased at the start of the rainy season, with species such as S. inornatus
      and S. boueti consisting of nearly 100% females. Sex ratios equalized when the
      first rainy-season generation emerged. population doubling times estimated from
      trap indices were approximately 12-16 days in two habitats (forest and riverine
      woodland).

PMID- 8994132
TI  - The effect of host blood in the in vitro transformation of bloodstream
      trypanosomes by tsetse midgut homogenates.
AB  - Midgut homogenates prepared from Glossina morsitans morsitans, that had
      previously been fed on different host blood samples, were tested for their
      abilities to transform bloodstream Trypanosoma brucei into procyclic (midgut)
      forms in vitro. Compared to rat and goat blood samples, eland blood had the least
      capacity to support trypanosome transformation, whereas buffalo blood showed
      intermediate capacity. Fractionation of rat blood showed the importance of the
      cellular portion since both rat and eland red blood cells (RBCs) supported the
      process. Virtually no transformation was observed in rat and eland plasma or
      serum fractions. Suspending rat blood cells in eland plasma led to a reduction in
      parasite transformation rates. Further experiments showed that the RBC membranes
      were also capable of supporting the process. These results clearly show the
      important role played by blood, especially the red blood cells, in the
      transformation of bloodstream trypanosomes. In addition, the low transformation
      rates observed in eland blood is due to an inhibitory factor(s) present in the
      plasma fraction.

PMID- 8994133
TI  - Histological and immunological reaction of cattle skin to first-instar larvae of
      Dermatobia hominis.
AB  - Six cattle that had earlier exposure to Dermatobia hominis were infested
      experimentally with first-instar larvae of the parasite. Skin biopsies taken at
      intervals were studied in wax and in plastic sections. The avidin-biotin
      peroxidase method was used to detect the presence and localization of host
      immunoglobulins (Igs) G and M and antigens of first and second instar larvae of
      Dermatobia hominis. The larvae penetrated actively through the skin and migrated
      towards the subcutaneous tissues. The great numbers of eosinophils suggest that
      they are the most important cell in mediating damage to D. hominis larvae. The
      immunoglobulins bound only to dead or moulting larvae in which access to binding
      sites may have been altered. This could represent a morphological manifestation
      of a mechanism that protects larvae from the host immune response. Large amounts
      of soluble antigens detected along the fistulous tract may be important in the
      maintenance of this tract by distributing the normal cicatrization process.

PMID- 8994134
TI  - The role of cattle as hosts of Glossina longipennis at Galana Ranch, south
      eastern Kenya.
AB  - Glossina longipennis were recorded visiting and engorging on cattle in an
      enclosure and on a single ox in a crush using transparent electrocuting nets in
      an incomplete ring. Of the total flies caught, 3-6% of males and 5-6% of females
      in the total catches were engorged (a feeding success rate of up to 16.6% and
      12.6%, respectively, depending on assumptions made about the proportion which had
      an opportunity to feed). Direct observation of tsetse from an observation pit
      showed 57% landing on the front legs, 13% on the hind legs, and 11% on the belly
      of the host. The largest number of bloodmeals was taken from the front legs,
      although only 14% of landings there terminated in feeding; a higher proportion of
      the flies alighting on the hind legs and flank succeeded in feeding (28% and 21%
      respectively). Glossina longipennis were attracted to targets baited with ox
      odour from an underground pit in a dose-dependent manner. Odour of humans was
      much less attractive to G. longipennis than that of oxen (for equivalent
      biomass). Analysis of bloodmeal samples from tsetse caught in two sites on the
      ranch showed that G. longipennis preferentially feeds on suids, bovids and
      hippopotamus.

PMID- 8994135
TI  - Trapping oestrid parasites of reindeer: the response of Cephenemyia trompe and
      Hypoderma tarandi to baited traps.
AB  - At 340-360 km North of the Arctic Circle in Norway, Hypoderma tarandi (L.) and
      Cephenemyia trompe (Modeer) females were caught in baited traps from 10 July to
      21 August. During three summers, adverse climatic conditions inhibited flight
      activity of these oestrids on 56-68% of the days. Flies were not caught prior to
      or after these dates, nor at winds above 8 m/s, temperatures below 10 degrees C,
      light intensities below 20,000 lux, or during periods of rain or snow. CO2-baited
      insect flight traps caught significantly more H.tarandi females than non-baited
      traps. However, neither a white reindeer hide or reindeer interdigital pheromone
      glands enhanced the attraction of CO2 to H.tarandi or C.trompe. Hypoderma tarandi
      females also were attracted to mobile people, but not to stationary individuals.
      There were no significant differences in the number of C.trompe or H.tarandi
      caught in CO2-baited traps in a birch/willow woods, on the treeless vidda (=
      tundra-like biome), or at woods:vida ecotone sites. Flies were caught in traps on
      days when the nearest reindeer herds were 25-100 km away. Significantly more
      H.tarandi and C.trompe were caught from 09.30 to 14.30 hours than from 14.30 to
      19.30 hours; no flies were caught from 20.00 to 07.00 hours (Norwegian Standard
      Time = NST). Because of CO2-baited traps caught from hundreds to thousands of
      mosquitoes, blackflies and Culicoides midges, when climatic conditions inhibited
      oestrid activity, reindeer aggregations and movements attributed to insect
      attacks during warm sunny days may be largely in response to attacks by H.tarandi
      and C.trompe.

PMID- 8994136
TI  - Trapping oestrid parasites of reindeer: the relative age, fat body content and
      gonotrophic conditions of Cephenemyia trompe and Hypoderma tarandi females caught
      in baited traps.
AB  - Dissection of flies caught in northern Norway revealed that only mated, gravid
      females of H.tarandi (L.) and larviparous C.trompe (Modeer) were caught in host
      mimicking CO2-baited traps. Trapped females had the same gonotrophic and fat body
      (FB) conditions as females caught on and around reindeer. Most trapped females of
      both species were of middle to old age, having only one-half to no FB reserves
      left and only a few to moderate numbers of eggs or larvae remaining. Most young
      females trapped also had previously oviposited or larviposited at least once, and
      some newly eclosed, mated females were present throughout the fly season. Based
      on the known location of reindeer herds, it was evident that trapped flies that
      had recently oviposited or larviposited had dispersed into the trapping area from
      25-100 km away. Declining FB reserves sustained wild-caught C.trompe females (and
      in utero larvae) in the laboratory for 14 days and H.tarandi females for 18 days.
      Reserve FB also was depleted during long flights. Females of both species that
      flew for the longest times (5.1-11.7 h) on a laboratory flight mill had low FB
      reserves, but nearly maximum numbers of eggs or larvae. Conversely, most females
      that flew for less than 5 h on the light mill had little or no FB remaining, and
      few eggs or larvae. The large FB reserves accumulated as larvae feed in the
      vertebrate host enable the non-feeding adults to survive and infect their hosts
      even after prolonged periods of flight-inhibiting climatic conditions.

PMID- 8994137
TI  - Trypanosome characterization by polymerase chain reaction in Glossina palpalis
      gambiensis and G.tachinoides from Burkina Faso.
AB  - Following the discovery of four cases of African human trypanosomiasis, an
      entomological survey was conducted along the Mouhoun river in southwest Burkina
      Faso to collect Glossina palpalis gambiensis and G.tachinoides. Among 226 flies
      dissected, 4.87% (eleven individuals) were infected in midgut or proboscis, but
      never in the salivary glands. Polymerase chain reaction analysis was undertaken,
      and was able to characterize all the proboscis infections, and half of the midgut
      infections. Only Trypanosoma simiae and T. vivax were found in the organs of
      infected flies, in single or mixed-species infections. Ten more flies, negative
      with parasitological examination, were tested with Trypanozoon primers and
      remained negative. The epidemiological significance of the absence of T.brucei
      group infections in wild tsetse populations and the presence of T.simiae in
      G.p.gambiensis are discussed.

PMID- 8994138
TI  - The occurrence of ixodid ticks on wild mink Mustela vision in England and Wales.
AB  - Four species of ticks found to infest 1391 American mink (Mustela vison) in
      Britain in five years were, in declining order of frequency, Ixodes hexagonus,
      Ixodes canisuga, Ixodes ricinus and Ixodes acuminatus. Ixodes hexagonus and I.
      canisuga occurred on 40% and 2.5% of mink respectively. Infestation rates (the
      proportion of infested mink) of adult females, nymphs and larvae were similar and
      tended to be lower in summer. The distribution of infestation size (the number of
      ticks per host) for adult females describes a negative binomial. The mean
      infestation size of nymphs varied with the sex of the host was 5.2 for males and
      4.2 for females. Mink are competent hosts for I.hexagonus.

PMID- 8994139
TI  - Distribution, prevalence and host associations of Hymenoptera parasitic on
      Calliphoridae occurring in flystrike in New Zealand.
AB  - Between 1920 and 1930, four species of parasitoid Hymenoptera (Tachinaephagus
      zealandicus, Alysia manducator, Nasonia vitripennis and Brachymeria ucalegon)
      were imported to New Zealand as an aid in the control of the blowflies causing
      myiasis in sheep (flystrike). Their long-term effects have never been
      investigated and the extent to which they were successful in establishing and
      enlarging their ranges has been given scant regard over the last 60 years. A long
      term epidemiological study of flystrike in New Zealand between 1984 and 1996
      obtained 4061 samples of blowfly larvae from flystruck sheep and carrion and
      overall 1.1% of these larval samples (most from the North Island) were found to
      be parasitized. Tachinaephagus zealandicus and A.manducator were present in field
      strikes, together with the endemic Aphaereta aotea recently found to be a
      parasite of calliphorids. The endemic species Phaenocarpa antipoda was found in
      association with carrion but not flystrike. Neither N.vitripennnis nor B.ucalegon
      were isolated from larvae in field strikes, the former because it parasitizes
      only pupae and the latter may be extinct as it has not been sighted since its
      introduction in 1919. It is concluded that if parasitoid wasps are able to locate
      and parasitize blowfly larvae on struck sheep, then their parasitism rate on more
      accessible larvae on carcases may be correspondingly greater. For this reason
      their scope for use in integrated management of flystrike could be increased by
      culturing and field release.

PMID- 8994140
TI  - Spectral sensitivity in the eyes of male and female Lutzomyia longipalpis
      sandflies.
AB  - Using electroretinogram recordings, the response of Lutzomyia longipalpis sandfly
      eyes to a range of wavelengths of light was measured, and spectral sensitivity
      determined. The eyes of both male and female adult sandflies were found to
      respond maximally to light in the ultraviolet region (at 340 nm) with a secondary
      peak in the blue-green-yellow region at 520 nm for females and 546 nm for males.
      The Mann-Whitney U test showed no significant differences between males and
      females at corresponding wavelengths.

PMID- 8994141
TI  - Mosquito seasonality and arboviral disease incidence in Murray Valley, southeast
      Australia.
AB  - Adult female mosquito populations were monitored at weekly intervals during
      spring-autumn (November-March) for 4 years (1991-95) using dry-ice-baited light
      traps at forty sites in the Murray Valley of Victoria, Australia. Among twenty
      species of mosquitoes collected, Culex annulirostris was the most abundant (66.6
      +/- 9.3%) followed by Cx australicus (15.3 +/- 7.7%). From a total of 476,682
      mosquitoes collected, nearly all were females and only 1295 (0.27%) were males.
      Mosquito population densities were generally higher in 1992-93 and 1993-94
      seasons than in 1991-92 and 1994-95 seasons. Greatest densities of Cx
      annulirostris and Cx australicus occurred in 1992-93, coinciding with outbreaks
      of Ross River (RR) and Barmah Forest (BF) arboviruses causing human
      polyarthritis. In the majority of shires, Cx australicus was the predominant
      species from spring to early summer (November and December), then was replaced by
      Cx annulirostris from mid-summer to autumn (January-April). In three shires,
      Aedes bancroftianus and Ae.sagax predominated during the early part of the
      season. Densities of both Cx annulirostris and Cx australicus were related to
      temperature. Cx australicus adults were found to be trapped when the mean ambient
      temperature exceeded 6 degrees C, with peak population recorded at 20 degrees C.
      Cx annulirostris adult density increased when the mean temperature rose above 12
      degrees C, reaching a peak during February and March when temperature exceeded 25
      degrees C. Cx annulirostris declined rapidly from April onwards, with no adult
      activity evident from May to November. Population densities of Aedes spp. were
      generally less than reported from earlier studies, possibly due to lower rainfall
      in spring and summer as well as reduced flood irrigation practices. In each year,
      a significant correlation was detected between Cx annulirostris density and RR
      virus incidence in humans. As Cx annulirostris is the predominant local mosquito
      species and feeds on a wide spectrum of host including man, it seems likely that
      Cx annulirostris is the major vector of RR in the inland Murray Valley region.

PMID- 8994142
TI  - Comparative fecundity and associated factors for two sibling species of the
      Anopheles gambiae complex occurring sympatrically in The Gambia.
AB  - For two sibling species of mosquitoes belonging to the Anopheles gambiae complex
      of malaria vectors, the effects of body size (wing length) and bloodmeal size
      (haematin excretion) on fecundity of wild females were investigated in The
      Gambia, West Africa. Freshly blood-fed individuals from sympatric populations of
      An.arabiensis and An.gambiae sensu stricto were sampled by collection at 07.00
      09.00 hours from within bednets during July/August 1993, at the beginning of the
      rainy season. The possible confounding effect of infection with Plasmodium
      parasites was removed by eliminating infected mosquitoes from the study samples.
      An.arabiensis females comprised 75% of the An.gambiae sensu lato population and
      were significantly larger (greater mean wing length) than those of An.gambiae
      s.s. mosquitoes. Mean egg production per female (for the subsequent gonotrophic
      cycle, excluding pre-gravids) for the two species was not significantly
      different, though the relationship between wing length and egg production showed
      An.gambiae s.s. to be more fecund than the An.arabiensis of the same size. Pre
      gravid An.gambiae s.s had consumed significantly smaller bloodmeals than gravid
      females but the mean wing length of these two gonotrophic categories was not
      significantly different. In contrast, An.arabiensis pre-gravids were smaller and
      had consumed smaller bloodmeals than the gravids.

PMID- 8994143
TI  - Feeding habits of Stomoxys spp. stable flies in a Kenyan forest.

PMID- 8994144
TI  - Larvicidal effectiveness of doramectin against natural warble (Hypoderma tarandi)
      and throat bot (Cephenemyia trompe) infections in reindeer.

PMID- 8994145
TI  - In vivo effect of a natural Aedes aegypti defensin on Brugia pahangi development.

PMID- 8994146
TI  - Predicting Quality of Well-being scores from the SF-36: results from the Beaver
      Dam Health Outcomes Study.
AB  - BACKGROUND: The SF-36 and the Quality of Well-being index (QWB) both quantify
      health status, yet have very different methodologic etiologies. The authors
      sought to develop an empirical equation allowing prediction of the QWB from the
      SF-36. DATA: They used empirical observations of SF-36 profiles and QWB scores
      collected in interviews of 1,430 persons during the Beaver Dam Health Outcomes
      Study, a community-based population study of health status, and 57 persons from a
      renal dialysis clinic. METHOD: The eight scales of the SF-36, their squares, and
      all pairwise cross-products, were used as candidate variables in stepwise and
      best-subsets regressions to predict QWB scores using 1,356 interviews reported in
      a previous paper. The resulting equation was cross-validated on the remaining 74
      cases and using the renal dialysis patients. RESULTS: A six-variable regression
      equation drawing on five of the SF-36 components predicted 56.9% of the observed
      QWB variance. The equation achieved an R2 of 49.5% on cross-validation using
      Beaver Dam participants and an R2 of 58.7% with the renal dialysis patients. An
      approximation for computing confidence intervals for predicted QWB mean scores is
      given. CONCLUSION: SF-36 data may be used to predict mean QWB scores for groups
      of patients, and thus may be useful to modelers who are secondary users of health
      status profile data. The equation may also be used to provide an overall health
      utility summary score to represent SF-36 profile data so long as the profiles are
      not severely limited by floor or ceiling effects of the SF-36 scales. The results
      of this study provide a quantitative link between two important measures of
      health status.

PMID- 8994147
TI  - A method to elicit utilities for interpersonal comparisons.
AB  - This paper examines how values should be assigned to health states when policy
      decisions must be made about who should receive treatment. The paper demonstrates
      that, if priority were to be assigned to those people who would benefit most from
      treatment, standard health-state utilities might fail to identify resource
      allocations that would maximize total health-related well-being in society. A new
      measurement instrument is proposed that is based on the direct comparison of the
      well-being achieved by different people in various health states and thus
      captures such community priorities. A sample of 72 health administration students
      used the instrument to evaluate speech and mobility dysfunctions as they
      afflicted hypothetical people who differed by gender, family status, and
      occupational type. This preliminary analysis indicates that the instrument is
      feasible to use, and that the valuations of respondents did, for some health
      conditions, significantly depend on the type of person afflicted.

PMID- 8994149
TI  - The importance of perspective in the measurement of quality-adjusted life years.
AB  - Scaling instruments for the measurement of quality-adjusted life years (QALYs)
      incorporate either a personal or an impersonal perspective on the benefits of a
      health intervention and either do or do not incorporate considerations of equity.
      This paper sets out three hypotheses concerning perspective and equity: 1) that
      more equally distributed benefits will be preferred to less equally distributed
      benefits; 2) that the preference value elicited for a health benefit will be
      greater when the respondent to a QALY questionnaire is a potential beneficiary;
      and 3) that, by comparison with personal preferences, individuals will be more
      concerned with the quantity than the quality of life in other people. These
      hypotheses were tested using two existing instruments and two other instruments
      that were created for this study. Results gave no support to the third
      hypothesis; some support to the first hypothesis, and strong support for the
      second hypothesis. It is concluded that perspective can significantly alter the
      values incorporated in a QALY instrument. The policy implications of the results
      are twofold. First, they give some support to the view that distributional
      consequences of health programs are of importance to the population and that they
      should be included in the evaluation of any health program. Second, they indicate
      that an evaluation should consider whether the health-state values to be obtained
      should incorporate an impersonal perspective reflecting the purely "social"
      judgment of a health planner or a perspective reflecting self-interest.

PMID- 8994148
TI  - The validity of QALYs: an experimental test of constant proportional tradeoff and
      utility independence.
AB  - Pliskin, Shepard, and Weinstein identified three preference conditions that
      ensure that quality-adjusted life years (QALYs) represent preferences over
      gambles over chronic health profiles. This paper presents an experimental test of
      the descriptive validity of two of these preference assumptions: utility
      independence and constant proportional tradeoff. Eighty students at the Stockholm
      School of Economics and 92 students at Erasmus University Rotterdam participated
      in the experiment. The results of the experiment support the descriptive validity
      of constant proportional tradeoff: both within groups and between groups constant
      proportional tradeoff could not be rejected. The results are less supportive of
      the descriptive validity of utility independence. Within-groups utility
      independence was rejected. Between-groups utility independence could not be
      rejected, but this may have been due to a lack of statistical power. Analysis of
      the individual responses revealed that without adjustment for imprecision of
      preference, 39 respondents (22.8%) satisfied constant proportional tradeoff.
      Twenty-three respondents (13.4%) satisfied utility independence without
      adjustment for imprecision of preference. However, because of the relative
      unfamiliarity of the respondents with both the health states to be evaluated and
      the methods of health-state-utility measurement, it is likely that the
      respondents' preferences were imprecise. Adjusted for imprecision of preference,
      the upper estimates of the proportions of respondents who satisfied constant
      proportional tradeoff and utility independence, respectively, were 90.1% (155
      respondents) and 75.6% (130 respondents). Pliskin et al. further derived that if
      an individual's preferences satisfy both constant proportional tradeoff and
      utility independence, then these preferences can be represented by a more
      general, risk-adjusted QALY model. Without adjustment for imprecision of
      preference, ten respondents (5.8%) satisfied both constant proportional tradeoff
      and utility independence. Adjusted for imprecision of preference, the upper
      estimate of the proportion of respondents who satisfied both constant
      proportional tradeoff and utility independence was 68.6% (118 respondents). The
      results of this study indicate that constant proportional tradeoff holds
      approximately. The evidence is much weaker for utility independence, however.
      This has important implications for the use of QALY-type measures in medical
      decision making.

PMID- 8994150
TI  - Can preference scores for discrete states be used to derive preference scores for
      an entire path of events? An application to prenatal diagnosis.
AB  - The authors conducted a study exploring whether preferences for sequences of
      events can be approximated by preferences for component discrete states. Visual
      analog-scale (VAS) and standard-gamble (SG) scores for a subset of the possible
      sequences of events (path states) and component temporary and chronic outcomes
      (discrete states) that can follow prenatal diagnostic decisions were elicited
      from 121 pregnant women facing a choice between chorionic villus sampling and
      amniocentesis. For individuals, preference scores for path states could not be
      predicted easily from discrete-state scores. Mean path-state VAS scores, however,
      were predicted reasonably accurately by multiple regression models (R2 = 0.85 and
      0.82 for two different anchoring schemes), with most measured scores lying within
      the 95% confidence intervals of the derived scores. It is concluded that, for
      individual patient decision making, preferences for path states should be
      elicited. When mean preference values for a population are sought, however, it
      may be reasonable to derive regression weights from a subset of respondents and
      then to apply those weights to preferences for discrete states elicited from a
      larger group.

PMID- 8994151
TI  - The influence of physician explanations on patient preferences about future
      health-care states.
AB  - OBJECTIVE: To determine the influence of alternative explanations by physicians
      of the purpose of a medical intervention (intubation and ventilatory support,
      IVS) on three types of patient preferences: desire for IVS, the length of time
      patients would find IVS acceptable, and the minimum probability of a good medical
      outcome patients would require before assenting to continued support with IVS.
      METHODS: Structured interviews were conducted with patients followed in a
      continuity care general medicine clinic at the Department of Veterans Affairs
      Medical Center, Portland, Oregon. Patients were asked to consider whether they
      would accept IVS at a future time. Patients were randomly assigned to one of two
      explanation conditions that differed in terms of their future medical contexts,
      that is, the degrees of specification of the nature of the medical condition
      patients were asked to consider. The general-explanation group was asked to
      consider the future medical context of " an unspecified medical condition"; the
      specific-explanation group was asked to consider the future medical context of "a
      severe pneumonia." Patients were asked three questions: 1) Would you accept IVS
      (yes or no)? 2) How long would you allow your physician to continue IVS?; and 3)
      After being on IVS for 2-3 days, what would be the minimum chance of recovery
      from the condition you would require before agreeing to continued IVS? "Chance of
      recovery" was defined for both groups as the probability that the patient would
      be able to leave the hospital and be able to take care of activities of daily
      living unassisted with minimal change in his or her mental state from the pre
      hospitalization status. RESULTS: Of 186 patients (mean age = 66.5 years; mean
      education = 12.7 years), 97 received the general explanation and 89 received the
      specific explanation about a severe pneumonia. Significantly fewer (p = 0.03)
      patients receiving the general explanation wanted physicians to intervene with
      IVS (general 94% vs specific 100%). Patients receiving the general explanation
      were willing to accept significantly fewer (p = 0.009) days of intubation
      (general 65 days vs specific 96 days). Significantly fewer (p < 0.0001) patients
      receiving the general explanation wanted physicians to continue IVS when the
      probability of a successful outcome was less than 50% (general 30% vs specific
      64%). CONCLUSION: Physician explanations--based on general (unspecified medical
      condition) vs specific (severe pneumonia) explanations--have a marked influence
      on the duration of IVS patients would permit and the probability of a good
      outcome required to continue IVS.

PMID- 8994152
TI  - Diagnostic value of signs and symptoms associated with peripheral arterial
      occlusive disease seen in general practice: a multivariable approach.
AB  - OBJECTIVES: To assess the diagnostic values of single and combined data from the
      history, physical examination, and medical record with regard to peripheral
      arterial occlusive disease (PAOD) in patients with leg complaints; to construct a
      multivariable model for the clinical diagnosis of PAOD by primary care
      physicians. SETTING: 18 general practice centers in The Netherlands. DESIGN:
      Cross-sectional comparison of signs, symptoms, and data from the medical record
      with the independently assessed ankle-brachial systolic pressure index (ABPI;
      cutoff point < 0.90); analysis: bivariate, multiple logistic regression (MLR).
      POPULATION: 2,455 individuals with leg complaints, aged 40.7-78.4 years; ABPI <
      0.90 present in 9.2% of legs (11.7% of individuals). OUTCOME MEASURES: Clinical
      variables: sensitivity, specificity, positive and negative predictive values
      (PV+, PV-), diagnostic odds ratio (OR); models: likelihood ratio test, area under
      the receiver operating characteristic curve (AUC). RESULTS: Bivariate analysis:
      highest sensitivity: age more than 60 years (77.3%); highest specificity: wounds
      or sores on toes and foot (99.7%); highest PV+: typical intermittent claudication
      (IC) (45.0%) (abnormal foot pulses 41.3%); highest PV-: strong pulses of both
      foot arteries (97.7%). MRL: the best-performing model (AUC 0.89) consisted of ten
      clinical variables: gender (OR 1.5), age more than 60 (OR 2.2); IC (OR 3.5);
      palpation of the skin temperature of the feet (OR 2.5), palpation of both foot
      pulses [OR 16.4 (abnormal) and 7.0 (doubtful)], auscultation of the femoral
      artery (OR 3.5); previous diagnosis of IHD (OR 1.7) or diabetes (OR 1.6), history
      of smoking (OR 2.1), and elevated blood pressure (OR 1.5). The range of predicted
      probabilities was 0.4-98%. The Hosmer-Lemeshow goodness-of-fit test indicated
      good overall fit (p = 52). CONCLUSIONS: Palpation of both foot pulses is the key
      procedure for the clinical diagnosis of PAOD. Traditional clinical evaluation
      enables the general practitioner to exclude the diagnosis of PAOD in many
      individuals with a high degree of certainly, to establish the diagnosis in a
      small group of patients, and to define a limited group of patients where
      supplementary noninvasive testing is appropriate. The MLR model can be used as a
      diagnostic checklist and as a reference for the physician's clinical hypothesis.

PMID- 8994153
TI  - Assessing rater performance without a "gold standard" using consensus theory.
AB  - This study illustrates the use of consensus theory to assess the diagnostic
      performances of raters and to estimate case diagnoses in the absence of a
      criterion or "gold" standard. A description is provided of how consensus theory
      "pools" information provided by raters, estimating rater competencies and
      differentially weighting their responses. Although the model assumes that raters
      respond without bias (i.e., sensitivity = specificity), a Monte Carlo simulation
      with 1,200 data sets shows that model estimates appear to be robust even with
      bias. The model is illustrated on a set of elbow radiographs, and consensus-model
      estimates are compared with those obtained from follow-up data. Results indicate
      that with high rater competencies, the model retrieves accurate estimates of
      competency and case diagnoses even when raters' responses are biased.

PMID- 8994154
TI  - The impact of computer-assisted test interpretation on physician decision making:
      the case of electrocardiograms.
AB  - This research investigated the effect of computer-assisted test interpretation
      (CATI) on physicians' readings of electrocardiograms (ECGs). The authors used an
      experimental method based on direct observations of 22 cardiologists, each
      reading 80 ECGs, for a total of 1,760 (of which 1,745 were used in the study).
      There were 40 sets of clinically-matched pairs of ECGs, one with CATI and one
      without. Reading time was observed and interpretation accuracy was measured by
      criterion-referenced aggregate scoring. To control for potential biases, the
      findings were subjected to multivariate analyses using ordinary least-squares
      regressions. The impact of CATI on cardiologists' readings of ECGs is
      demonstrably beneficial: the main empirical conclusion of this study is that,
      compared with conventional interpretation, the use of computer-assisted
      interpretation of ECGs cuts physician time by an average of 28% and significantly
      improves the concordance of the physician's interpretation with the expert
      benchmark, without increasing the false-positive rate. Moreover, CATI is the most
      accurate and saves the most time when the ECGs have many unambiguous diagnoses.
      Given that computers alone cannot perform the task of cardiovascular diagnosis,
      and that cardiologists' ECG interpretations are greatly enhanced by ubiquitous
      CATI technology, it appears that the best approach is one that combines person
      and machine.

PMID- 8994155
TI  - Determining transition probabilities from mortality rates and autopsy findings.
AB  - The Markov process is a useful tool for modeling the natural history of disease,
      which is becoming increasingly important as new diagnostic tests increase the
      detectability of early-stage disease. The accuracy of a Markov model, however,
      depends on the accuracy of the estimates for the transition probabilities between
      different stages of disease. Because these estimates are usually based on "expert
      opinion" or small cohort studies, they are subject to imprecision and bias. The
      authors describe an alternative method of estimating transition probabilities
      from the stage distribution of disease observed at the time of death and age
      specific mortality rates from other causes. In addition, they prove that the
      transition probabilities are unique given certain assumptions about how they
      change with age. Finally, they illustrate the method using population-based data
      for prostate cancer.

PMID- 8994156
TI  - A comparison of parametric and nonparametric approaches to ROC analysis of
      quantitative diagnostic tests.
AB  - Receiver operating characteristic (ROC) analysis, which yields indices of
      accuracy such as the area under the curve (AUC), is increasingly being used to
      evaluate the performances of diagnostic tests that produce results on continuous
      scales. Both parametric and nonparametric ROC approaches are available to assess
      the discriminant capacity of such tests, but there are no clear guidelines as to
      the merits of each, particularly with non-binormal data. Investigators may worry
      that when data are non-Gaussian, estimates of diagnostic accuracy based on a
      binormal model may be distorted. The authors conducted a Monte Carlo simulation
      study to compare the bias and sampling variability in the estimates of the AUCs
      derived from parametric and nonparametric procedures. Each approach was assessed
      in data sets generated from various configurations of pairs of overlapping
      distributions; these included the binormal model and non-binormal pairs of
      distributions where one or both pair members were mixtures of Gaussian (MG)
      distributions with different degrees of departures from binormality. The biases
      in the estimates of the AUCs were found to be very small for both parametric and
      nonparametric procedures. The two approaches yielded very close estimates of the
      AUCs and the corresponding sampling variability even when data were generated
      from non-binormal models. Thus, for a wide range of distributions, concern about
      bias or imprecision of the estimates of the AUC should not be a major factor in
      choosing between the nonparametric and parametric approaches.

PMID- 8994157
TI  - Test-indication curves.
AB  - Test-indication curves (TICs) are tools for determining whether a test is
      indicated for a given patient. They apply the threshold approach of Pauker and
      Kassirer in graphic form. These curves are composed of two parts: the raw curve,
      which plots posttest probability versus pretest probability (given values for
      specificity and sensitivity); and the final curve, in which three straight lines
      are added to the raw curve by the clinician to generate a TIC for a given
      treatment threshold. In the final curve, the complete range of pretest
      probability is segregated into three zones, corresponding to the three groups
      described by Pauker and Kassirer: those patients in whom disease is assumed to be
      present and who are thus best treated empirically; at the other extreme, those
      who require neither testing nor treatment; and, finally, those in the middle, for
      whom the test is indicated, since the decision to treat would be based on the
      test result. Thus the clinician could consult the TIC and determine with
      certainty whether the test should be employed for a given patient. It also could
      be modified with ease for a different patient, with a different set of threshold
      values. TICs provide a complete, visual interpretation of a test's diagnostic
      power, in the context of a given treatment threshold. They foster an intuitive
      comprehension of Pauker and Kassirer's method, and offer the clinician a facile
      means to prove that a test is indicated in a given setting. By promoting the use
      of exactly those tests that are indicated, TICs can help spare the patient the
      cost, burden, and risk of unnecessary testing, and help spare the physician the
      cost, burden, and risk of interpreting inconclusive test results.

PMID- 8994158
TI  - Good technologies gone bad: how and why the cost-effectiveness of a medical
      intervention changes for different populations.
AB  - Cost-effectiveness (CE) ratios vary considerably, not only across interventions,
      but within single interventions. Using a simple decision-tree model of the treat
      vs no-treat decision to organize the analysis, four potential errors leading to
      these within-treatment differences in CE ratios are identified. These errors
      arise from estimates relating to 1) prior probabilities of disease; 2) treatment
      efficacies; 3) costs of treatment; and 4) patient preferences. Systematic biases,
      where present, suggest overuse of medical interventions. For diagnostic tests,
      two additional potential sources of error are considered (using a simple decision
      tree incorporating both test and treat decisions). These involve 5) sensitivity
      and specificity of the diagnostic test and 6) inappropriate choice of "cutoff" to
      determine abnormal patients, in part arising from errors in estimating prior
      probability of disease.

PMID- 8994159
TI  - The effect of helical pitch and beam collimation on the lesion contrast and slice
      profile in helical CT imaging.
AB  - A model is presented in this paper to describe how the contrast of a
      reconstructed object and slice sensitivity profile are affected by (1) the table
      speed or helical pitch, (2) the x-ray collimations, (3) the size of the object,
      (4) the alignment between the reconstructed slice and the object, (5) the
      distance of the object from the axis of rotation, and (6) the helical CT
      reconstruction algorithm employed. This contrast model is validated by both
      computer simulations and experiments. With this model, the contrast of a
      reconstructed object, slice sensitivity profile, and the longitudinal MTF can be
      accurately predicted. The optimal scan strategy and the point of diminishing
      returns can be determined prior to scanning. Several conclusions can be drawn
      from this model. First, overlapping reconstruction significantly improves overall
      scan contrast sensitivity of helical CT. Second, with a given x-ray collimation,
      low pitch helical scans provide better longitudinal resolutions. Third, with a
      given volume coverage rate (i.e., a given table speed), narrow collimation high
      pitch helical scans provide better longitudinal resolutions than wide collimation
      low pitch ones and therefore are recommended for high-contrast thin-slice
      applications. A lesion conspicuity model is also established.

PMID- 8994161
TI  - An evaluation of the Y2O3:Eu3+ scintillator for application in medical x-ray
      detectors and image receptors.
AB  - The suitability off a Y2O3:Eu3+ scintillator for use in radiation detectors and
      medical image receptors was studied. Y2O3:Eu3+ was used in the form of laboratory
      prepared screens of different coating thicknesses. The x-ray luminescence
      efficiency of the screens was measured for tube voltages between 50-200 kVp and
      in both transmission and reflection modes of observation. The intrinsic x ray to
      light conversation efficiency (nc) and other parameters of the Y2O3:Eu3+ phosphor
      material related to optical scattering, absorption, and reflection were
      determined. These were used in the calculation of the image transfer
      characteristics, MTF and zero frequency DQE, for various screen coating
      thicknesses and x-ray tube voltages. The light emission spectrum of Y2O3:Eu3+ was
      measured (narrow band peak at 613 nm) and its spectral compatibility to the
      spectral sensitivity of several commonly employed optical photon detectors was
      determined. The x-ray luminescence efficiency varied with x-ray tube voltage,
      attaining maximum value at about 80 kVp for all screen thicknesses. It also
      varied with coating thickness reaching 25 microW m(-2)/mR s(-1) and 18 microW m(
      2)/mR s(-1) at 175 mg/cm2 for reflection and transmission modes, respectively.
      The intrinsic x ray to light conversion efficiency and the image transfer
      characteristics were found to be comparable to several commercially used
      phosphors: nc = 0.095, MTF0.05 ranged between 10 and 25 line pairs per mm and
      peal values of DQE(0) varied between 0.33 and 0.14 in the coating thickness and
      kVp ranges useful for x-ray imaging. Spectral compatibility to some red sensitive
      optical photon detectors was excellent (0.9 or better). Results indicated that
      Y2O3:Eu3+ is a medium to high overall performance material that could be used in
      medical x-ray detectors and image receptors.

PMID- 8994160
TI  - Sinusoidal modulation analysis for optical system MTF measurements.
AB  - The modulation transfer function (MTF) is a commonly used metric for defining the
      spatial resolution characteristics of imaging systems. While the MTF is defined
      in terms of how an imaging system demodulates the amplitude of a sinusoidal
      input, this approach has not been in general use to measure MTFs in the medical
      imaging community because producing sinusoidal x-ray patterns is technically
      difficult. However, for optical systems such as charge coupled devices (CCD),
      which are rapidly becoming a part of many medical digital imaging systems, the
      direct measurement of modulation at discrete spatial frequencies using a
      sinusoidal test pattern is practical. A commercially available optical test
      pattern containing spatial frequencies ranging from 0.375 cycles/mm to 80
      cycles/mm was sued to determine the MRF of a CCD-based optical system. These
      results were compared with the angulated slit method of Fujita [H. Fujita, D.
      Tsia, T. Itoh, K. Doi, J. Morishita, K. Ueda, and A. Ohtsuka, "A simple method
      for determining the modulation transfer function in digital radiography," IEEE
      Trans. Medical Imaging 11, 34-39 (1992)]. The use of a semiautomated profiled
      iterated reconstruction technique (PIRT) is introduced, where the shift factor
      between successive pixel rows (due to angulation) is optimized iteratively by
      least-squares error analysis rather than by hand measurement of the slit angle.
      PIRT was used to find the slit angle for the Fujita technique and to find the
      sine-pattern angle for the sine-pattern technique. Computer simulation of PIRT
      for the case of the slit image (a line spread function) demonstrated that it
      produced a more accurate angle determination than "hand" measurement, and there
      is a significant difference between the errors in the two techniques (Wilcoxon
      Signed Rank Test, p < 0.001). The sine-pattern method and the Fujita slit method
      produced comparable MTF curves for the CCD camera evaluated.

PMID- 8994162
TI  - A multiple wavelength algorithm in color image analysis and its applications in
      stain decomposition in microscopy images.
AB  - Stains have been used in optical microscopy to visualize the distribution and
      intensity of substances to which they are attached. Quantitative measures of
      optical density in the microscopic images can in principle be used to determine
      the amount of the stain. When multiple dyes are used to simultaneously visualize
      several substances to which they are specifically attached, quantification of
      each stain cannot be made using any single wavelength because attenuation from
      the several stain components contributes to the total optical density. Although
      various dyes used as optical stains are perceived as specific colors, they, in
      fact, have complex attenuation spectra. In this paper, we present a technique for
      multiple wavelength image acquisition and spectral decomposition based upon the
      Lambert-Beer absorption law. This algorithm is implemented based on the different
      spectral properties of the various stain components. By using images captured at
      N wavelengths, N components with different colors can be separated. This
      algorithm is applied to microscopy images of doubly and triply labeled prostate
      tissue sections. Possible applications are discussed.

PMID- 8994163
TI  - Practical application of a scan-rotate equalization geometry to mammography.
AB  - The presence of dense fibroglandular tissue within the breast is the most
      significant cause of failure to detect breast cancer with mammography. The dense
      tissue often produces a range of exposure which exceeds the useful dynamic range
      of film-screen mammography. It has been shown that equalization radiography
      overcomes the latitude limitations of film-screen imaging. Equalization
      compensates for regional variations in x-ray transmission within the patient
      through spatial modulation of the entrance exposure. We have proposed rotary
      scanning equalization radiography (RSER), a scan-rotate geometry for efficient
      equalization radiography. In RSER the image receptor is exposed by repeated scans
      of a source-modulated fan beam. The fan beam is rotated with respect to the
      patient between scans. Numerical simulations and theoretical analysis have shown
      that the superposition of exposure from appropriately modulated fan beams at a
      variety of angles is an entrance exposure that effectively equalizes the film
      exposure. The design and characteristics of a prototype RSER imaging system are
      described. Anthropomorphic breast phantom images are used to determine the
      improvement in image contrast obtained with RSER, the expected tube loading, and
      the presence of artifacts. RSER increases the fraction of the breast imaged with
      high contrast (at least 90% of peak gradient) from 46% (conventional mammography)
      to 80%. Subjective examination of the phantom images show that RSER achieves
      image quality very similar to that of much less efficient equalization geometries
      with only 2.7 times greater tube loading than conventional mammography. As
      predicted by theoretical analysis of exposure artifacts in RSER, the prototype
      RSER system is relatively immune to artifacts. Exposure artifacts were
      demonstrated for extreme variations in x-ray transmission within the patient.
      These results show that RSER is an efficient, practical means of overcoming the
      latitude limitations of film-screen mammography, and improving the detection of
      breast cancer.

PMID- 8994164
TI  - Comparison of x-ray cross sections for diagnostic and therapeutic medical
      physics.
AB  - The purpose of this technical report is to make available an up-to-date source of
      attenuation coefficient data to the medical physics community, and to compare
      these data with other more familiar sources. Data files from Lawrence Livermore
      National Laboratory (in Livermore, CA) were truncated to match the needs of the
      medical physics community, and an interpolation routine was written to calculate
      a continuous set of cross sections spanning energies from 1 keV to 50 MeV.
      Coefficient data are available for elements Z = 1 through Z = 100. Values for
      mass attenuation coefficients, mass-energy-transfer coefficients, and mass-energy
      absorption coefficients are produced by a single computer subroutine. In addition
      to total interaction cross sections, the cross sections for photoelectric,
      Rayleigh, Compton, pair, and some triplet interactions are also produced by this
      single program. The coefficients were compared to the 1970 data of Storm and
      Israel over the energy interval from 1 to 1000 keV; for elements 10, 20, 30, 40,
      50, 60, 70, and 80, the average positive difference between the Storm and Israel
      coefficients and the coefficients reported here are 1.4%, 2.7%, and 2.6%, for the
      mass attenuation, mass energy-transfer, and mass-energy absorption coefficients,
      respectively. The 1969 data compilation of mass attenuation coefficients from
      McMaster et al. were also compared with the newer LLNL data. Over the energy
      region from 10 keV to 1000 keV, and from elements Z = 1 to Z = 82 (inclusive),
      the overall average difference was 1.53% (sigma = 0.85%). While the overall
      average difference was small, there was larger variation (> 5%) between cross
      sections for some elements. In addition to coefficient data, other useful data
      such as the density, atomic weight, K, L1, L2, L3, M, and N edges, and numerous
      characteristic emission energies are output by the program, depending on a single
      input variable. The computer source code, written in C, can be accessed and
      downloaded from the World Wide Web at: http:@www.aip.org/epaps/epaps.html [E
      MPHSA-23-1977].

PMID- 8994165
TI  - On the reporting of mass contrast in CAD research.
AB  - As research efforts for developing computer-aided diagnosis (CAD) schemes of
      digitized mammograms increase and interscheme results are compared, the desire to
      establish an acceptable consistent reporting protocol of the distribution of
      abnormal characteristic is becoming an issue. "Mass contrast" is very important
      and frequently reported in current CAD studies. In this report, 100 verified mass
      regions were analyzed systemically using 6 different definitions of "mass
      contrast." Measured variability in mass contrast was demonstrated by the
      distribution shift in this group masses. The need for universally accepted and
      largely standardized descriptors of objects of interest is clearly demonstrated.

PMID- 8994166
TI  - Intensity modulation optimization, lateral transport of radiation, and margins.
AB  - Intensity modulation provides greatly increased control, leading to superior dose
      distributions with a potential for improved clinical outcome. It also allows us
      to compensate for deviations from the expected patterns in dose distributions
      caused by the lateral transport of radiation. This is important not only to
      produce more homogeneous dose distributions in the target volume but also, more
      importantly, to allow a reduction in the margins for the penumbra and a
      corresponding reduction in the volume of normal tissue irradiated. Potentially,
      this would permit escalation of doses to higher levels and further improve local
      control for the same or lower normal tissue complications. The intensity
      modulated treatment design process, regardless of the specific method used,
      involves the tracing of rays from the source of radiation through the target
      volume. Intensities of rays are adjusted iteratively in an attempt to produce a
      desired homogeneous dose within the target volume, while at the same time
      striving to maintain normal tissue exposure within the limits of tolerance. If
      the lateral transport of scattered radiation is ignored, as is commonly done
      because of the complexities of incorporating it, the resulting dose distribution
      within the target volume may be considerably different from the anticipated
      pattern. This would be particularly true if there are high gradients in fluence
      patterns within the field to shield a normal anatomic structure. Similarly, the
      lateral transport of radiation would lead to a dose deficit just inside the
      boundary of the planning target volume (PTV) and a dose excess just outside it.
      The conventional remedy to make up for the loss of dose near the boundaries,
      thereby ensuring complete coverage of the target volume, would be to employ a
      margin for the "penumbra." We demonstrate that, with intensity modulation, we
      have an important new tool to improve target coverage, namely an appropriate
      increase in fluence just inside the boundary. Most suitably, a combination of
      increased fluence and a smaller than conventional margin should be employed. We
      have used an iterative scheme to compensate for lateral transport in the
      intensity modulation optimization process. In each iteration, the intensity
      distribution is first designed ignoring lateral transport. At the end of each
      iteration, the dose distribution is calculated using a pencil beam convolution
      method, thereby incorporating lateral transport and revealing the deviations from
      the anticipated dose distribution caused by lateral transport. In the next
      iteration, ray intensities are further adjusted to rectify the deviations. In
      general, only a few iterations are needed to adequately account for the lateral
      transport of radiation. We have applied this method to intensity-modulated
      prostate treatment plans and demonstrate that this methodology allows the use of
      smaller margins, improves target dose homogeneity, and provides greater
      protection for normal tissues. We examine the variation of the magnitude of the
      gain from one patient to another. The methodology described in this paper has
      been introduced into routine clinical use.

PMID- 8994167
TI  - Super-Monte Carlo: a 3-D electron beam dose calculation algorithm.
AB  - An electron beam dose calculation algorithm has been developed which is based on
      a superposition of pregenerated Monte Carlo electron track kernels. Electrons are
      transported through media of varying density and atomic number using electron
      tracks produced in water. The perturbation of the electron fluence due to each
      material encountered by the electrons is explicitly accounted for by considering
      the effect of (i) varying stopping power, (ii) scattering power, and (iii)
      radiation yield. For each step of every electron track, these parameters affect
      the step length, the step direction, and for energy deposited in that step
      respectively. Dose distributions in both homogeneous water and nonwaterlike
      phantoms, and heterogeneous phantoms show consistent agreement with "standard"
      Monte Carlo results. For the same statistical uncertainty in broad beam
      geometries, this new calculation method uses a factor of 9 less computation time
      than a full Monte Carlo simulation.

PMID- 8994168
TI  - Cerebral tumor volume calculations using planimetric and eigenimage analysis.
AB  - Volume determination in cerebral tumors requires accurate and reproducible
      segmentation. This task has been traditionally accomplished using planimetric
      methods which define the boundary of the lesion using thresholding and edge
      detection schemes. These methods lack accuracy and reproducibility when the
      contrast between the lesion and surrounding tissue is not maximized. Because of
      this limitation contrast agents are used providing reproducible results for the
      enhancing portion of the lesion. A novel approach for volume determination has
      been developed (eigenimage filter) which segments a desired feature (tissue type)
      from surrounding undesired features in a sequence of images. This method corrects
      for partial volume effects and has been shown to provide accurate and
      reproducible volume determinations. In addition, the eigenimage filter does not
      require the use of contrast and has the capability to segment a lesion into
      multiple regions. This allows different components of the lesion to be included
      and monitored in treatment. In this study planimetric methods and the eigenimage
      filter were compared for segmenting cerebral tumors and determining their
      volumes. The planimetric methods were reproducible in determining volumes for the
      enhancing portion of the lesion with interobserver percent differences < 8% and
      intraobserver percent differences < 4%. The eigenimage filter had interobserver
      percent differences < 7% and intraobserver percent differences < 3%. In the
      eigenimage procedure both the enhancing portion of the lesion as well as
      additional regions within the lesion were identified. Comparing the results
      obtained from the two methods demonstrated good agreement for presurgical studies
      (percent differences < 9%). When comparing postsurgical studies large differences
      were seen. In the postsurgical studies the eigenimage method allowed multiple
      regions to be followed in subsequent MRI and in two patients showed a volume
      change that suggested tumor recurrence more clearly. Since the amount of
      information obtained using the eigenimage filter may allow a more complete
      assessment of the lesion, it is suggested that it could improve the clinical
      evaluation of cerebral tumors.

PMID- 8994169
TI  - The accuracy of dose localization for an image-guided frameless radiosurgery
      system.
AB  - A compact X-band accelerator mounted on a robotic arm is under development for
      frameless stereotaxic radiosurgery. The therapy beam is aimed at the lesion by an
      imaging system comprised of two diagnostic x-ray cameras that view the patient
      during treatment. Patient position and motion are measured by the cameras and
      communicated in real time to the robotic arm for beam targeting and patient
      motion tracking. The tests reported here measured the pointing accuracy of the
      therapy beam and the present targeting and tracking capability of the imaging
      system. The results show that the system achieves the same level of targeting
      precision as conventional frame-based radiosurgery.

PMID- 8994170
TI  - An improved neutron collimator for brain tumor irradiations in clinical boron
      neutron capture therapy.
AB  - To improve beam penetration into a head allowing the treatment of deeper seated
      tumors, two neutron collimators were built sequentially and tested for use in the
      clinical boron neutron capture therapy (BNCT) program at the epithermal neutron
      irradiation facility of the Brookhaven Medical Research Reactor. The collimators
      were constructed from lithium-impregnated polyethylene, which comprises Li2CO3
      powder (approximately 93% enriched isotopic 6Li) uniformly dispersed in
      polyethylene to a total 6Li content of 7.0 wt. %. The first collimator is 7.6 cm
      thick with a conical cavity 16 cm in diameter on the reactor core side tapering
      to 8 cm facing the patient's head. The second collimator is 15.2 cm thick with a
      conical cavity 20 cm in diameter tapering to 12 cm. A clinical trial of BNCT for
      patients with malignant brain tumors is underway using the first collimator.
      Results of phantom dosimetry and Monte Carlo computations indicate that the new
      15.2 cm thick collimator will improve the neutron beam penetration. Thus, the
      second collimator was made and will be used in an upcoming clinical trial. In-air
      and in-phantom mixed-field dosimetric measurements were compared to Monte Carlo
      computations for both collimators. The deeper penetration is achieved but at a
      sacrifice in beam intensity. In this report, a performance comparison of both
      collimators regarding various fluence rate and absorbed dose distributions in a
      head model is presented and discussed.

PMID- 8994171
TI  - Characteristics of a scintillator-based daily quality assurance device for
      radiation oncology beams.
AB  - A plastic scintillator based device marketed as a "DCT 444" is investigated for
      daily quality assurance (QA) of radiation beams. Variations in DCT responses were
      studied for three identical devices with beam, energy, distance, dose, dose rate,
      and orientations. The effects of gantry, collimator, and patient support assembly
      (PSA) rotations were investigated at photon energies of 6, 10, and 18 MV and
      electron energies in the range of 5-20 MeV from three different linear
      accelerators. The short and long term linearity, reproducibility, and radiation
      damage were also investigated in kilovoltage and megavoltage beams. Results
      indicate that the DCT response is linear with dose and dose rate, but shows
      directional dependence for all beams. The response is dependent on its
      orientation and the angle of rotations of collimator, gantry, and PSA of the
      linear accelerator. When the collimator is rotated through 0-36 degrees, the DCT
      response varied within +/- 4.5% and +/- 7.2% for the 6 MV and 18 MV beams,
      respectively. With PSA rotation, deviations up to +/- 11% were noted. The DCT
      response is symmetric across 0 degrees and peaks at +/- 60% PSA angle for all
      accelerators and beam energies. The effect of backscattering medium on DCT
      response is noted for all beams but significant for kilovoltage beams. A
      deviation as high as 30% was observed when DCT was placed on a thick polystyrene
      phantom. The long term stability studied over 25 months showed varied signal
      losses possibly due to radiation damage. However, there is no noticeable signal
      loss over a short period of time (2-4 weeks). The lightweight DCT device is
      linear with dose and dose rate, stable, and easy to operate. It stores ten
      readings that can be downloaded to a personal computer. This study indicates that
      DCT-444 is a suitable QA tool for central axis dose measurement. However, proper
      precaution is needed as this device exhibits directional and positional
      dependence. For a meaningful QA result of a radiation unit, the daily QA setup
      geometry should be identical to that used for calibration of the DCT device.

PMID- 8994172
TI  - Alignment of multi-segmented anatomical features from radiation therapy images by
      using least square fitting.
AB  - A least square fitting algorithm for alignment of multi-open-curved segments and
      point pairs of anatomical features obtained from both portal images and
      simulation radiographs has been developed for patient position verification in
      radiation therapy. A coordinate system associated with each curved segment pair
      is constructed so that the discrepancies of each segment pair can be obtained
      easily. The algorithm allows users to select not only multiple curve pairs but
      also individual point pairs on the important anatomic landmarks. The
      misregistration is measured by the sum of the position deviation of individual
      point pairs and ordinate discrepancies of all segment pairs from their
      corresponding coordinate systems. A mathematical minimization method is applied
      to seek an optimal transformation for matching of all segment and/or point pairs
      involved. The reliability of the algorithm has been tested with both phantom and
      clinical images. The test results indicate that the typical errors are less than
      1 mm and 1 degrees in translation and rotation, respectively.

PMID- 8994173
TI  - Comment on "Magnetic repulsion of linear contaminates" [Med. Phys. 23, 953-955
      (1996)].

PMID- 8994174
TI  - A source model for efficient brachytherapy computations with Monte Carlo.
AB  - Monte Carlo techniques have the potential for producing accurate brachytherapy
      dose distributions in heterogeneous finite geometries. However, for routine
      clinical use, computational speed must be adequate. A fast, all-particle, CT
      based Monte Carlo code called PEREGRINE is being developed at Lawrence Livermore
      National Laboratory for radiation treatment planning. As one feature, the code
      will produce accurate dose distributions from brachytherapy sources in
      heterogeneous geometries. For efficiency, brachytherapy sources in this model are
      treated as points or line segments. Radiation is emitted with the proper energy
      spectrum and (perhaps anisotropic) angular distribution. In particular, for
      anisotropic emission the polar angle is determined by a random-number driven
      empirical function constructed from a source's measured or precomputed fluence
      emission pattern. Source model parameters are presented for iodine and iridium
      sources. While designed for the PEREGRINE program, this source model can be used
      in any Monte Carlo code.

PMID- 8994175
TI  - A genetic algorithm for the optimization of prostate implants.
AB  - A genetic algorithm (GA) is presented for the optimization of template- and
      ultrasound-guided prostate implants. The end points for optimization are
      incorporated in an objective function of separable cardinal utility terms. As an
      application of the GA, the minimum 103Pd total source strength required to
      deliver a given dose was correlated with the average dimension for prostate
      implants carried out under the current template and seed spacing protocols.
      Significant improvements in quality were observed, in terms of both the minimum
      peripheral dose and tumor cell surviving fractions, when GA-optimized implants
      were compared to the corresponding unoptimized implants for given target volumes.
      In addition, numerical simulation of source displacements indicates that the
      dosimetric and radiobiologic advantages of GA optimization can tolerate a
      reasonable level of seed placement uncertainties observed clinically. In summary,
      the GA application provides an automated design strategy for prostate implant
      planning, and at the same time affords the potential for systematic optimization
      of a set of end points that can sustain practical variations.

PMID- 8994176
TI  - The summer of 1982.

PMID- 8994177
TI  - Respiratory support in refractory ARDS.

PMID- 8994178
TI  - Postoperative nausea and vomiting--its pathophysiology and management.

PMID- 8994179
TI  - Prophylactic administration of ondansetron in emergency intraabdominal
      operations.
AB  - Efficiency of ondansetron, a selective 5-HT3 receptor antagonist, in prevention
      of postoperative nausea and vomiting in 40 ASA I-II patients who will undergo
      emergency intraabdominal operations is studied in a randomized double-blind and
      placebo controlled study. Patients of no premedication are administered 4 mg i.v.
      ondansetron or placebo (saline) before induction. Thiopental (4 mg/kg) was used
      for induction, succinylcholine (2 mg/kg) for muscular relaxation, and 50% nitrous
      oxide in oxygen and isoflurance (0.8-1.5%) for the maintenance of anesthesia, and
      fentanyl and norcuron were administered when necessary. Vital signs were closely
      monitored and recorded during anesthesia and early postoperative period. Study is
      carried out during postoperative 0-1 h, 1-2 h and 2-24 h periods. Nausea scores
      and emesis were recorded during 0-1 and 1-2 h periods. Ondansetron was found
      significantly more effective than placebo (p < 0.05 and p < 0.05). Although is
      was effective during 2-24 h period, the difference was not statistically
      significant (p > 0.05). No significant difference was observed between the groups
      in terms of vital findings, laboratory findings and side effects (p > 0.05).
      Therefore it is concluded that administration of prophylactic i.v. ondansetron to
      patients undergoing emergency intraabdominal operations is effective in
      prevention of nausea and vomiting without any significant side effects.

PMID- 8994180
TI  - Severe neck burns and laryngeal mask airway for frequent general anesthetics.
AB  - Securing the airways in a patient suffering severe neck burns or its sequalae may
      present a challenge to the most experienced anesthesiologist. We investigate the
      utility of the Laryngeal Mask Airway (LMA) in this situation. We report on
      success, failure of complications of LMA insertion at the induction of general
      anesthesia in 23 patients of a Major Burns Unit and compare our results to our
      records of patients intubated endotracheally in the Unit. 14 out of 15 patients
      with neck burns had a LMA inserted with no difficulty or complications, while
      difficult endotracheal intubations in patients with neck burns were more frequent
      with statistical significance compared to patients with intact necks. LMA
      insertion seems to ignore the difficulties met with endotracheal intubation in
      this context.

PMID- 8994181
TI  - Modified Laryngeal Mask Airway--a useful aid to fiberoptic intubation.
AB  - Modified Laryngeal Mask (MLMA) aided fiberoptic intubation (FOI) using larger
      than 6 mm ID endotracheal tube was studied in 25 adult patients and compared to
      unaided FOI in another 25 patients. MLMA aided FOI was successful in 96% cases
      compared to 56% in the unaided group. Furthermore, the time to successful
      intubation was increased by 67.1% when FOI was attempted without MLMA aid which
      was statistically significant (P < 0.001). However, maximum fluctuations in the
      heart rate and mean arterial pressure in the immediate post-intubation period
      were statistically insignificant between the groups. We conclude that MLMA not
      only adds to success rate of FOI but also significantly reduce the FOI time in
      adult patients.

PMID- 8994182
TI  - Combinations of drugs for induction and maintenance of anesthesia and sedation of
      the critically ill.

PMID- 8994183
TI  - Functional role of a conformationally flexible homopurine/homopyrimidine domain
      of the androgen receptor gene promoter interacting with Sp1 and a pyrimidine
      single strand DNA-binding protein.
AB  - The androgen receptor (AR) gene promoter does not contain the TATA or CAAT box,
      but it contains a long (approximately 90-bp) homopurine/homopyrimidine (pur/ pyr)
      stretch immediately upstream of the Sp1-binding GC box site. This pur-pyr stretch
      is conserved at the same proximal position in the rat, mouse, and human AR gene
      promoters. Mutation of this region results in a 3-fold decline in promoter
      activity, indicating an important regulatory function. Examination of the
      conformational state of the AR pur/pyr region with the single-strand-specific S1
      nuclease showed that it is capable of forming a non-B DNA structure involving
      unpaired single strands. Fine mapping of the S1-sensitive site revealed an
      unsymmetric cleavage pattern indicative of an intramolecular triple helical H
      form DNA conformation. Electrophoretic mobility shift analyses showed that the
      pur/pyr region of the AR promoter can bind a novel pyrimidine single-strand
      specific protein (ssPyrBF) and also a double-strand DNA-binding protein. Both
      oligonucleotide cross-competition and antibody supershift experiments established
      that the double-strand binding protein is equivalent to Sp1. Deoxyribonuclease I
      (DNase I) footprinting analysis showed multiple Sp1-binding to the pur/pyr site
      and a weaker Sp1 interaction to this region compared with the adjacently located
      GC box, where Sp1 functions to recruit the TFIID complex. These results suggest
      that the pur/pyr domain of the AR gene can serve to attract additional Sp1
      molecules when it exists in the double-stranded B-DNA conformation. However,
      binding of ssPyrBF and the resultant stabilization of the non-B DNA structure is
      expected to prevent its interaction with Sp1. We speculate that in the TATA-less
      AR gene promoter, multiple weak Sp1 sites at the pur/pyr region adjacent to the
      GC box can provide a readily available source of this transcription factor to the
      functional GC box, thereby facilitating the assembly of the initiation complex.

PMID- 8994185
TI  - Transgenic mice overexpressing the beta 1-adrenergic receptor in adipose tissue
      are resistant to obesity.
AB  - The ratio of alpha- to beta-receptors is thought to regulate the lipolytic index
      of adipose depots. To determine whether increasing the activity of the beta 1
      adrenergic receptor (AR) in adipose tissue would affect the lipolytic rate or the
      development of this tissue, we used the enhancer-promoter region of the adipocyte
      lipid-binding protein (aP2) gene to direct expression of the human beta 1 AR cDNA
      to adipose tissue. Expression of the transgene was seen only in brown and white
      adipose tissue. Adipocytes from transgenic mice were more responsive to beta AR
      agonists than were adipocytes from nontransgenic mice, both in terms of cAMP
      production and lipolytic rates. Transgenic animals were partially resistant to
      diet-induced obesity. They had smaller adipose tissue depots than their
      nontransgenic littermates, reflecting decreased lipid accumulation in their
      adipocytes. In addition to increasing the lipolytic rate, overexpression of the
      beta 1 AR induced the abundant appearance of brown fat cells in subcutaneous
      white adipose tissue. These results demonstrate that the beta 1 AR is involved in
      both stimulation of lipolysis and the proliferation of brown fat cells in the
      context of the whole organism. Moreover, it appears that it is the overall beta
      AR activity, rather than the particular subtype, that controls these phenomena.

PMID- 8994184
TI  - Isoform variable action among thyroid hormone receptor mutants provides insight
      into pituitary resistance to thyroid hormone.
AB  - Resistance to thyroid hormone (RTH) is due to mutations in the beta-isoform of
      the thyroid hormone receptor (TR-beta). The mutant TR interferes with the action
      of normal TR to cause the clinical syndrome. Selective pituitary resistance to
      thyroid hormone (PRTH) results in inappropriate TSH secretion and peripheral
      sensitivity to elevated thyroid hormone levels. Association of the PRTH phenotype
      with in vitro behavior of the mutant TR has proved elusive. Alternative exon
      utilization results in two TR-beta isoforms, TR-beta 1 and TR-beta 2, which
      differ only in their amino termini. Although the TR-beta 1 isoform is ubiquitous,
      the TR-beta 2 isoform is found predominantly in the anterior pituitary and brain.
      To date, in vitro evaluation of RTH mutations has focused on the TR-beta 1
      isoform. Site-directed mutagenesis was used to create several PRTH (R338L, R338W,
      V349M, R429Q, I431T) and generalized RTH (delta 337T, P453H) mutations in both TR
      beta isoforms. The ability of mutant TRs to act as dominant negative inhibitors
      of wild type TR-beta function on positive and negative thyroid hormone response
      elements (pTREs and nTREs, respectively) was evaluated in transient transfection
      assays. PRTH mutants had no significant dominant negative activity as TR-beta 1
      isoforms on pTREs found in peripheral tissues or on nTREs found on genes
      regulating TSH synthesis. PRTH mutants, in contrast, had strong dominant negative
      activity on these same nTREs as TR-beta 2 isoforms. Cotransfected retinoid X
      receptor-alpha was required for negative T3 regulation via the TR-beta 1 isoform
      but was not necessary for negative regulation via the TR-beta 2 isoform in CV-1
      cells. The differing need for retinoid X receptor cotransfection demonstrates two
      distinct negative T3-regulatory pathways, one mediated by the TR-beta 1 and the
      other mediated by TR-beta 2. The selective effect of PRTH mutations on the TR
      beta 2 isoform found in the hypothalamus and pituitary vs. the TR-beta 1 isoform
      found in peripheral tissues suggests a molecular mechanism for the PRTH disorder.

PMID- 8994186
TI  - Neuroendocrine regulation of the hypothalamic pituitary adrenal axis by the
      nurr1/nur77 subfamily of nuclear receptors.
AB  - The present study was designed to examine the role of the nurr1/nur77 subfamily
      of nuclear receptor transcription factors in the regulation of the
      hypothalamic/pituitary/adrenal axis at the neuroendocrine level. We demonstrate
      that this nuclear receptor subfamily can regulate the expression of the CRF and
      POMC genes by interacting with a specific cis-acting sequence in their proximal
      promoter regions. To examine the physiological significance of this response, we
      have focused on the POMC gene. We provide evidence that nurr1 and nur77 are
      rapidly induced by CRF in primary pituitary cells and that this induction is
      mimicked by forskolin in an anterior pituitary cell line. Further, we demonstrate
      that both nurr1- and forskolin-dependent induction of a POMC-chloramphenicol
      acetyltransferase reporter gene are inhibited by mutation of the nurr1-binding
      site within the POMC promoter and that this site alone can confer cAMP
      responsiveness to a heterologous promoter. Finally, we provide evidence that the
      nurr1/nur77 response sequence is pivotal to both nurr1/nur77-dependent positive
      regulation and glucocorticoid receptor-dependent negative regulation of the POMC
      gene. These data strongly support the conclusion that the nurr1/nur77 subfamily
      plays an important coordinate neuroendocrine-regulatory role at all levels of the
      hypothalamic/pituitary/adrenal axis.

PMID- 8994187
TI  - Estradiol-binding mechanism and binding capacity of the human estrogen receptor
      is regulated by tyrosine phosphorylation.
AB  - We have investigated the effects of tyrosine phosphorylation on the estradiol
      binding mechanism and binding capacity of the human estrogen receptor (hER). The
      wild type hER and a point mutant form of the hER, in which tyrosine 537 was
      mutated to phenylalanine (Y537F hER), were expressed in Sf9 insect cells. The
      wild type hER, but not the Y537F hER, reacted with a anti-phosphotyrosine
      monoclonal antibody, indicating that tyrosine 537 was the only tyrosine
      phosphorylated on the hER. Scatchard and Hill analyses of the the binding
      interaction of [3H]estradiol with the wild type hER indicated that the addition
      of millimolar phosphotyrosine, but not tyrosine, phosphate, or phosphoserine,
      abolished the cooperative binding mechanism of the hER. These observations are
      consistent with the idea that phosphotyrosine blocks dimerization and site-site
      interactions between the hER monomers. The wild type hER bound 10-fold more
      [3H]estradiol than the Y537F hER. Treatment of the purified wild type hER with a
      tyrosine phosphatase decreased the binding capacity of the hER by approximately
      90%, whereas, a serine/threonine phosphatase had no effect. The estrogen-binding
      capacity of the tyrosine-dephosphorylated hER was completely restored by
      rephosphorylation of tyrosine 537 with p60c-src, a tyrosine kinase. These results
      indicate that p60c-src can restore estrogen binding to the tyrosine
      dephosphorylated hER and that dimerization and cooperative site-site interaction
      of the hER occur via a phosphotyrosine-binding interaction.

PMID- 8994188
TI  - Antiprogestin inhibition of cell cycle progression in T-47D breast cancer cells
      is accompanied by induction of the cyclin-dependent kinase inhibitor p21.
AB  - Progestin antagonists inhibit the proliferation of progesterone receptor-positive
      cells, including breast cancer cells, by G1 phase-specific actions, but the
      molecular targets involved are not defined. Reduced phosphorylation of pRB, a
      substrate for G1 cyclin-dependent kinases (CDKs) in vivo, was apparent after 9 h
      treatment of T-47D breast cancer cells with the antiprogestins RU 486 or ORG
      31710, accompanying changes in S phase fraction. Although the abundance of cyclin
      D1, Cdk4, and Cdk6 did not decrease cyclin D1-associated kinase activity was
      reduced by approximately 50% at 9-18 h. Similarly, cyclin E-associated kinase
      activity decreased by approximately 60% at 12-24 h in the absence of significant
      changes in the abundance of cyclin E and Cdk2. The CDK inhibitor p21 increased in
      mRNA and protein abundance and was present at increased levels in cyclin D1 and
      cyclin E complexes at times when their kinase activity was decreased. Increased
      p21 protein abundance was observed in another antiprogestin-sensitive cell line,
      BT 474, but not in two breast cancer cell lines insensitive to antiprogestins.
      These data suggest increased p21 abundance and concurrent inhibition of CDK
      activity as a mechanism for antiprogestin induction of growth arrest.
      Antiprogestin effects on proliferation were markedly reduced after ectopic
      expression of cyclin D1, indicating that inhibition of cyclin D1 function is a
      critical element in antiprogestin inhibition of proliferation. However, these
      data also implicate regulation of cyclin E function in antiprogestin regulation
      of cell cycle progression.

PMID- 8994190
TI  - Characterization of structural and functional properties of human 17 beta
      hydroxysteroid dehydrogenase type 1 using recombinant enzymes and site-directed
      mutagenesis.
AB  - Human 17 beta-hydroxysteroid dehydrogenase (17-HSD) type 1 catalyzes the
      conversion of the low activity estrogen, estrone, into highly active estradiol,
      both in the gonads and in target tissues. The present study was carried out to
      characterize the dimerization, microheterogeneity, and phosphorylation of human
      17-HSD type 1 and to evaluate the current model of hydride transfer and substrate
      recognition of the enzyme, based on its x-ray structure. 17-HSD type 1 is a
      homodimer consisting of noncovalently bound subunits, and the data in the present
      study indicate an exceptionally strong association between the monomers
      [dissociation constant (Kd) < 5 pmol/monomers liter]. Furthermore, substitutions
      constructed at the hydrophobic dimer interface always resulted in inactive
      aggregates of the protein. The enzyme was shown to be phosphorylated by protein
      kinase A exclusively at Ser134 only in vitro. However, in contrast to previous
      suggestions, phosphorylation of Ser134 was shown to play no role in the activity
      or microheterogeneity of human 17-HSD type 1. The presence of microheterogeneity
      in the recombinant enzyme also indicates that it does not result from the
      frequent protein polymorphism previously found for the enzyme. In line with the x
      ray structure and the proposed catalytic mechanism of the enzyme, our results
      indicate that Ser142, Tyr155, and Lys159 are all critical for hydride transfer in
      human 17-HSD type 1. In contrast, the proposed interaction between His221,
      Glu282, and the 3-OH group of the steroid at the substrate recognition helix
      could not be shown to exist. Neither of these residues plays a critical role in
      the catalytic action of the enzyme in cultured cells.

PMID- 8994189
TI  - Adenovirus-mediated gene transfer of dominant negative ras(asn17) in 3T3L1
      adipocytes does not alter insulin-stimulated P13-kinase activity or glucose
      transport.
AB  - Recent studies suggest that the ras-map kinase and PI3-kinase cascades converge.
      We sought to determine whether PI3-kinase is downstream of ras in insulin
      signaling in a classic insulin target cell. We generated a recombinant adenovirus
      encoding dominant negative ras by cloning the human H-ras cDNA with a ser to asn
      substitution at amino acid 17 (ras(asn17)) into the pACCMVpLpA vector and
      cotransfecting 293 cells with the pJM17 plasmid containing the adenoviral genome.
      Efficiency of gene transfer was assessed by infecting fully differentiated 3T3L1
      adipocytes with a recombinant adenovirus expressing beta-galactosidase (beta
      gal); greater than 70% of cells were infected. Infection of adipocytes with
      ras(asn17) resulted in 10-fold greater expression than endogenous ras. This high
      efficiency gene transfer allowed biochemical assays. Insulin stimulation of ras
      GTP formation was inhibited in ras(asn17)-expressing cells. Map kinase gel
      mobility shift revealed that insulin (1 UM) or epidermal growth factor (100
      ng/ml) resulted in the appearance of a hyperphosphorylated species of p42 map
      kinase in uninfected cells and those expressing beta-gal but not in cells
      expressing ras(asn17). In contrast, insulin increased IRS-1-associated PI3-kinase
      activity approximately 10-fold in control cells and high level overexpression of
      ras(asn17) did not impair this effect. Similarly, insulin and epidermal growth
      factor activation of total (no immunoprecipitation) PI3-kinase activity in both
      cytosol and total cellular membranes and insulin stimulation of glucose transport
      were not affected by expression of dominant negative ras. Thus, adenovirus
      mediated gene transfer is effective for studying insulin signaling in fully
      differentiated insulin target cells. Inhibition of ras activation abolishes
      insulin-stimulated phosphorylation of map kinase but does not affect insulin
      stimulation of PI3-kinase activity. In normal cell physiology, PI3-kinase does
      not appear to be downstream of ras in mediating the actions of insulin.

PMID- 8994191
TI  - Repression of cAMP-induced expression of the mouse P450 17 alpha-hydroxylase/C17
      20 lyase gene (Cyp17) by androgens.
AB  - In primary cultures of mouse Leydig cells, testosterone represses the cAMP
      induced de novo synthesis of P450 17 alpha-hydroxylase/C17-20 lyase (P450c17)
      protein and the accumulation of P450c17 mRNA, via an androgen receptor (AR)
      mediated mechanism. To examine the mechanism by which androgens repress the cAMP
      induced expression of the mouse Cyp17 gene, constructs containing 5'-flanking
      sequences of the mouse Cyp17 linked to the chloramphenicol acetyltransferase
      (CAT) reporter gene were cotransfected into MA-10 tumor Leydig cells with a mouse
      AR expression plasmid. In the presence of dihydrotestosterone, the cAMP-induced
      expression of a reporter construct containing -1021 bp of Cyp17 promoter
      sequences was repressed. In contrast, no repression by dihydrotestosterone was
      observed when the -1021 bp Cyp17-CAT construct was cotransfected with a human AR
      expression plasmid missing the second zinc finger of the DNA-binding domain,
      indicating that DNA binding is involved in AR-mediated repression of Cyp17
      expression. Analysis of deletions -346 bp of 5'-flanking region of the mouse
      Cyp17 promoter are sufficient to confer androgen repression of the cAMP-induced
      expression of Cyp17. Deoxyribonuclease I footprinting analysis indicated that the
      AR interacts with sequences between -330. and -278 bp of the Cyp17 promoter. This
      region overlaps with the previously identified cAMP-responsive region located
      between -346 and -245 bp of the Cyp17 promoter. These results suggest that AR
      mediated repression involves binding of the AR to sequences in the cAMP
      responsive region of the Cyp17 promoter, possibly interfering with the binding of
      the protein(s) that mediate cAMP induction of Cyp17.

PMID- 8994193
TI  - In memory of Milena Kemali: the scientist, the person.

PMID- 8994192
TI  - Human endometrial stromal cells express novel isoforms of the transcriptional
      modulator CREM and up-regulate ICER in the course of decidualization.
AB  - Decidualization of human endometrial stromal (ES) cells in culture can be
      triggered by a sustained elevation of intracellular cAMP for several days and is
      characterized by activation of the cAMP-responsive decidual PRL (dPRL) gene
      promoter. We investigated the expression of the cAMP response element (CRE)
      binding protein CREB, and the modulators CREM (cAMP response element modulator)
      and ICER (inducible cAMP early repressor), in relation to decidualization of ES
      cells. We isolated all four known ICER isoforms from ES cells, which differ by
      the presence or absence of the small exon gamma and the presence of either DNA
      binding domain (DBD) I or II. Of the various CREM isoforms, we cloned six
      transcript species, all containing DBD I. These were the known repressor CREM
      alpha, the potential activator CREM-tau 2 alpha, and four novel forms whose
      reading frames were blocked upstream of the DBD. Two of these forms contained a
      novel exon psi, which is 100 bp in length, resides downstream of the first
      protein-coding exon of the CREM gene, and introduces an early in-frame stop
      codon. Surprisingly, in cotransfection assays, all four novel CREM isoforms were
      potent inhibitors of protein kinase A-stimulated transcription of a reporter gene
      construct driven by a CRE. By in vitro transcription/translation of all six CREM
      cDNAs, we demonstrated internal translation initiation at three different
      methionine residues, giving rise to novel short and very short C-terminal
      proteins comprising DBD I. These proteins bound to a cAMP response element as
      homodimers or as heterodimers with each other or with CREB. Immunofluorescence
      showed nuclear localization of C-terminal CREM proteins expressed from all six
      CREM cDNAs. Comparison of undifferentiated and decidualized ES cells showed no
      difference in the level of expression of any of the CREM transcript species.
      Likewise, CREB was evenly expressed between the two populations. In contrast,
      ICER transcripts were strongly up-regulated in decidualized ES cells in parallel
      with the induction of dPRL expression. It appears paradoxical that in vivo, in
      response to a permanent cAMP stimulus, ICER is up-regulated without displaying
      negative autoregulation of its own gene or suppression of the dPRL promoter.
      Elevated ICER levels in decidualized ES cells may be indicative of the presence
      of overriding amounts of transcriptional activators such as full length CREM-tau
      or CREB which, in turn, upon cAMP-induced phosphorylation, contribute to the
      induction of the dPRL gene.

PMID- 8994195
TI  - Basic connectivity of the cerebral cortex and some considerations on the corpus
      callosum.
AB  - Studies on the connectivity of the cerebral cortex have lent strong support to
      the idea that the cortex is an associative network in which information is stored
      by ways of Hebbian cell assemblies. One of the main arguments for this is the
      elaborated system of cortico-cortical long-range connections which allows distant
      regions of the cortex to interact. Part of this system is the corpus callosum,
      which is responsible for the co-operation of the two cortical hemispheres. The
      following points are interesting with regard to interhemispheric co-operation:
      (1) the callosal system includes fewer neurons than the system of
      intrahemispheric long-range connections; (2) the mirror image activity induced by
      the callosal system may be advantageous for the ignition of cell assemblies; (3)
      the fibres of the corpus callosum differ considerably in thickness, which may be
      considered as anatomical evidence for more direct co-operation of the two
      hemispheres in some tasks rather than in others; and (4) a complex relationship
      between brain size and fibre thickness becomes evident in the corpus callosum, in
      which only some fibres seem to compensate for the longer conduction times in
      larger brains.

PMID- 8994194
TI  - The concept of transcortical cell assemblies: a key to the understanding of
      cortical lateralization and interhemispheric interaction.
AB  - According to Hebb, elements of higher cognitive processes, such as concepts,
      words and mental images, are realized in the brain as cortical cell assemblies,
      i.e. large and strongly connected neuron populations that form functional units.
      Neurons belonging to such assemblies may be scattered over wide cortical areas,
      and some cell assemblies may even comprise neurons of both hemispheres
      (transcortical assemblies). If full activation (ignition) of an assembly leads to
      fast circulation of neuronal activity in the assembly, this process should be
      visible in high-frequency cortical responses. Some evidence will be reviewed that
      cell assembly ignition indeed leads to changes in high-frequency cortical
      responses which can be recorded in the EEG and MEG. Within the cell assembly
      framework, the question of cortical laterality translates into the question of
      how neurons of transcortical assemblies are balanced between the hemispheres.
      This approach allows for different degrees of laterality. Recent evidence is
      summarized that the degree of laterality indeed differs between language units.
      For example, the cortical representation of certain words appears to be strongly
      lateralized to the left hemisphere while those of others are less lateralized. If
      neurons of both hemispheres are part of one assembly bihemispheric processing
      should lead to a processing advantage compared to processing in the dominant
      hemisphere alone. The latter appears to be the case for lexical processing, as
      revealed by recent behavioral studies. In conclusion, the cell assembly-framework
      suggests a more fine-grained description of the issue of cortical laterality; it
      is not appropriate to ask whether "modules" supporting higher cortical functions
      are located either in the left or right hemisphere. Rather, it appears fruitful
      to ask how the neurons of transcortical cell assemblies are balanced between the
      hemispheres.

PMID- 8994196
TI  - Lateral asymmetries in infancy: implications for the development of the
      hemispheres.
AB  - Cerebral asymmetry of cognitive processing of stimulus information is commonly
      viewed as a neocortical phenomenon. However, a number of lines of evidence give
      innate asymmetry of brainstem motivating systems, which anticipate experience, a
      key role. Spontaneous asymmetries of gesture and emotion can be observed in
      infants, who entirely lack language and visuo-constructive skills. Motives for
      communication in early life may direct subsequent development of complementary
      cognitive systems in left and right hemispheres. In split-brain monkeys,
      lateralized motive sets, intentions for manipulation by one hand, can determine
      which hemisphere will see and learn. Evolutionary antecedents of cerebral
      asymmetry appear to affect motivation, social signalling and bimanual
      coordination, with secondary effect in perceptual processing and learning. The
      hemispheres of adult humans differ in links with neurochemical system that
      regulate motor initiatives, exploration and attention, and the
      approach/withdrawal balance in social encounters. Asymmetries in emotional and
      communicative behaviour in infancy support evidence that an Intrinsic Motive
      Formation emerging in the embryo human brain stem regulates asymmetries in
      development and in functioning of the cerebral cortex.

PMID- 8994197
TI  - Structure, functional and cerebral asymmetry: in vivo morphometry of the planum
      temporale.
AB  - Using high-resolution magnetic resonance (MR) imaging, the normal left-right
      asymmetry of the planum temporale (PT) can be quantified accurately and reliably
      in the intact human brain. The following main results have emerged from MR
      measurements of individual direction and degree of PT asymmetry. (1) Normal left
      handers are less left-lateralized than normal right-handers, without significant
      gender effects. This confirms a structural-functional correlation in cerebral
      asymmetry. (2) The aforementioned handedness difference in PT asymmetry is also
      found in pairs of normal monozygotic twins discordant for handedness. Thus,
      structural brain asymmetry may not be genetically determined. (3) Whereas right
      handed patients with developmental deficits of phonological processing have been
      reported to show decrease PT asymmetry, musicians with perfect pitch display
      exaggerated leftward asymmetry. Thus, increasing leftward asymmetry of auditory
      related cortices covering the PT may be correlated with the processing capacity
      for certain auditory features. Studies of the PT as a structural marker of
      cerebral asymmetry will continue to contribute to a better understanding of the
      phylogeny and ontogeny of laterality.

PMID- 8994199
TI  - Cellular, morphometric, ontogenetic and connectional substrates of anatomical
      asymmetry.
AB  - Although anatomical cerebral asymmetry appears in all animals that have been
      examined, its link to functional lateralization is not clear. In an attempt to
      further elucidate this relationship between structure and function, we have
      compared, in rats and humans, brains that have asymmetric architectonic areas to
      those that are symmetric. We have found that (1) asymmetry is the result of the
      production of a small side rather than the production of a large side; (2)
      architectonic asymmetry is the result of changes in the total numbers of neurons
      rather than cell-packing density; (3) events occurring early in corticogenesis-
      specifically during the period of progenitor cell proliferation and/or death--are
      important for the formation of asymmetric cortical areas; and (4) symmetric
      brains have relatively greater numbers of callosal fibers and more patches of
      termination than their asymmetric counterparts. These results, taken together,
      suggest that if anatomic asymmetry underlies functional lateralization, it may
      have more to do with the different organization of symmetric and asymmetric
      brains, rather than simply which hemisphere (or brain region) is larger.

PMID- 8994198
TI  - Structural asymmetries in the human forebrain and the forebrain of non-human
      primates and rats.
AB  - Possible asymmetries of the following structures were studied: volumes of total
      human hemispheres, cortex and white matter volumes in post-mortem- (unknown
      handedness) and living brains (male right-handers); volumes of the rat primary
      visual cortex, its mon- and binocular subfields, its layer iv and the density of
      myelinated fibres in layer iv; transmitter receptor densities (NMDA, AMPA,
      kainate and GABAA receptors) in sensorimotor regions of the rat cortex; volume of
      the motor cortex and the 3D-extent of the central sulcus in the post-mortem-
      (unknown handedness) and living human brain (male right-handers); petalia of the
      hemispheres in human (male right- and left-handers) and chimpanzee brains.
      Histological, MRI and receptor autoradiographic techniques were used. With the
      notable exceptions of the transmitter receptors and the total primary visual
      cortex in rats and the hemispheres in chimpanzees, which do not show any
      significant directional asymmetry, all other parameters studied are
      asymmetrically distributed between the right- and left hemispheres. The regional
      distribution pattern and the degree of asymmetry of frontal and occipital petalia
      in living human brains differ between right- and left-handers.

PMID- 8994200
TI  - Lateralization of brain mechanisms underlying automatic and controlled forms of
      spatial orienting of attention.
AB  - Unilateral Spatial Neglect (USN) can be considered as a defect in spatial
      orienting of attention toward the half space contralateral to the damaged
      hemisphere. Since the classical work of Brain, W.R. Brain 64:224-272 (1941),
      several authors have emphasized that this defect is definitely more frequent and
      severe in patients with right brain damage, but the reason for this hemispheric
      asymmetry has remained controversial. Several investigations conducted with
      different experimental paradigms in different laboratories have shown that only
      automatic orienting of attention toward stimuli arising in the half space
      contralateral to the damaged hemisphere is disrupted in USN, whereas controlled,
      volitional orienting can be more or less completely spared. The hypothesis that
      at the level of the right hemisphere, spatial orienting of attention may be
      mainly prompted by automatic mechanisms may, therefore, be advanced. By contrast,
      the left hemisphere might play a leading role in mechanisms underlying volitional
      orienting of attention. According to this model, recovery from USN could be due
      to substitution of the lost automatic orienting mechanisms with the spread
      volitional orienting mechanisms subserved by the intact left hemisphere.

PMID- 8994201
TI  - Spatial stimulus-response compatibility in callosotomy patients and subjects with
      callosal agenesis.
AB  - Subjects with partial or complete defects of the corpus callosum, either
      congenital or acquired, performed a choice reaction time (RT) task involving a
      right or left key-press response to a light presented at random in the right or
      left hemifield. Like normal subjects, all of them exhibited two additive effects
      typical of these tasks: the spatial stimulus-response compatibility effect
      (faster RT for stimuli and responses matched for side), and the hand placement
      effect (longer RT for responses performed with crossed hands). Two subjects with
      a complete callosal defect, one acquired and the other congenital, showed a third
      effect, not present in normal subjects, consisting of a marked advantage for RT
      of responses with hand anatomically ipsilateral to the stimulus, independent of
      both stimulus-response compatibility and hand placement. These findings can be
      interpreted according to a hierarchical model of information processing assuming
      that, in the absence of the corpus callosum, the matching of the mental codes for
      the stimulus and response sets takes place solely in the hemisphere receiving the
      stimulus, with a subsequent rapid-intrahemispheric or slow-interhemispheric
      transmission of the response command to the appropriate motor centers.

PMID- 8994202
TI  - Laterality and types of dyslexia.
AB  - The right shift theory of handedness and cerebral specialization suggests that
      there is an underlying substrate of random lateral asymmetries in all higher
      animals and a specific factor in humans which increases the probability of left
      hemisphere advantage. The specific factor displaces the random distribution along
      a continuum of asymmetry in favour of the left hemisphere and the right hand. The
      distribution of handedness in families can be explained if the shift to
      dextrality depends on a single gene, rs +, when the frequency of the gene is
      estimated from the proportion of dysphasics with unilateral lesions of the left
      versus the right hemisphere. The gentoype proportions suggested a genetic
      balanced polymorphism with heterozygote advantage for laterality and ability.
      Application of the model to developmental dyslexia led to the hypothesis that
      both homozygotes (rs -- and rs ++ genotypes) are at risk for reading. The
      critical question was whether the type of cognitive problem differs as expected,
      speech based processing for the rs -- and non-speech based for the rs ++. The
      former should include more left and mixed handers, while the latter should be
      more strongly dextral than controls. Evidence for this double dissociation
      between type of cognitive disability and type of handedness has been found in
      poor readers and in other samples.

PMID- 8994203
TI  - Diencephalic asymmetries.
AB  - Structural asymmetry in diencephalic regions has been reported in a number of
      studies since the pioneering observations by Kemali and Braitenberg, Atlas of the
      frog's brain. Springer Verlag: 1969. Anatomical differences between the left and
      right habenulae have been identified in many lower vertebrate species. While
      there are few reports of structural asymmetry in the dorsal thalamus, there is
      evidence that asymmetrical thalamofugal projections can be induced in the visual
      system of chicks by lateralized sensory stimulation prior to hatching. Finally,
      there have been consistent reports of differences between and right sides of the
      hypothalamus in their sensitivity to the effects of circulating gonadal hormones
      in rats. In most cases, these asymmetries are sex-linked and correspond to a
      lateralization of function. Although the significance of these diencephalic
      asymmetries is still enigmatic, their existence indicates that asymmetry is not a
      phylogenetically recent feature of the brain, and the left-right differences in
      the brain may be mediated by a common ontogenetic mechanism and may underlie the
      development of highly specialized functions.

PMID- 8994204
TI  - Developmental asymmetries in experimental animals.
AB  - The early embryo orients to the antero-posterior axis and differentiates along
      this, and the dorso-ventral and lateral axes. From Drosophila melanogaster,
      detailed knowledge has accrued of how segmentation and dorso-ventral
      differentiation proceed, and of their genic control, mostly by selector and
      homeobox (Hox) genes. The study of the control of lateral differentiation,
      instead, has been largely neglected. Yet handed asymmetry (the "obvious"
      asymmetries of, for example, heart, lung, anatomical features of the nervous
      system, etc.) is basic and, possibly, universal. In the mouse, two genes control
      this: the iv gene which, when mutated, leads to random, in the place of biased,
      asymmetry and so to random situs inversus viscerum: and the inv mutation which,
      by contrast, results in 100% situs inversus. Both mutants act as autosomal
      recessives. Human situs inversus is heterogeneous and may be akin to that
      produced by the murine iv gene. In spite of situs inversus, there is no shift of
      hand preference; but there is no information on other lateralization, e.g. of
      language or of dermatoglyphic patterns. Handed asymmetry is known in Drosophila,
      but there is no information on its control. In the experimental nematode,
      Caenorhabditis elegans, asymmetry arises when differently programmed cells
      arrange themselves to the two body sides, and is present already at the six-cell
      stage; and even the major sensory neurons chains along the body axis are
      distributed unequally on the two sides of the worm. Experimentally, by embryonic
      micro-manipulation or the use of chemical mutagens, the normal and invariate
      direction of handed asymmetry can be reversed.

PMID- 8994205
TI  - Does prenatal stress impair coping and regulation of hypothalamic-pituitary
      adrenal axis?
AB  - Prenatally stressed (PS) human infants and experimental animals show attentional
      deficits, hyperanxiety and disturbed social behavior. Impaired coping in
      stressful situations in adult PS monkeys and rodents is associated with
      dysregulation of the HPA axis, characterized by decreased feedback inhibition of
      corticotropin-releasing hormone (CRH) and prolonged elevation of plasma
      glucocorticoids in response to stress. PS rats have higher levels of CRH in the
      amygdala, fewer hippocampal glucocorticoid receptors and less endogenous opioid
      and GABA/BDZ (benzodiazepine) inhibitory activity. The mechanisms by which
      maternal stress induce these long-lasting changes in the developing fetal
      neuroaxis remain to be elucidated. It is suggested that impaired coping in
      stressful situations and dysregulation of the hypothalamic-pituitary-adrenal
      (HPA) axis, result from the action of maternal hormones released during stress on
      the developing fetus. The similarities in coping behavior and dysregulation of
      the HPA axis in PS animals to those in humans with depression, suggest that
      gestational stress, at a critical time during fetal development, may increase the
      propensity to develop this condition.

PMID- 8994206
TI  - Hypothalamic-pituitary-adrenal responses to brief social separation.
AB  - Involuntary separation from close social companions is widely held to lead to
      pathophysiological outcomes. Presumably, the relationship with, or category of,
      the separated individual determines the nature of the physiological response.
      Here, experiments examining the consequences of brief involuntary separation on
      the activity of the stress-responsive hypothalamic-pituitary-adrenal (HPA) system
      are reviewed. Only those studies designed specifically to assess the effect of
      the absence of the social partner are considered. Evidence for HPA activation in
      response to social separation has been obtained in a number of species; yet, many
      studies find no effect of separation of affiliative partners on HPA activity. The
      occurrence of an HPA response to separation does not appear to be related to the
      phylogenetic position or cognitive capacity of the species studied, nor is it a
      universal response to mother-infant separation. Rather, it is suggested that the
      pattern of results can be largely understood in the context of attachment.
      Separation of partners exhibiting signs of emotional attachment leads to an
      immediate and persistent HPA response, whereas separation of partners that are
      affiliative, but do not exhibit attachment, has little or no effect on HPA
      activity.

PMID- 8994207
TI  - Brain cooling during transient focal ischemia provides complete neuroprotection.
AB  - A review of the effects of reducing brain temperature on ischemic brain injury is
      presented together with original data describing the systematic evaluation of the
      effects of brain cooling on brain injury produced by transient focal ischemia.
      Male spontaneously hypertensive rate were subjected to transient middle cerebral
      artery occlusion (TMCAO; 80, 120 or 160 min) followed by 24 h of reperfusion.
      During TMCAO, the exposed skull was bathed with isotonic saline at various
      temperatures to control skull and deeper brain temperatures. Rectal temperature
      was always constant at 37 degrees C. Initial studies indicated that skull
      temperature was decreased significantly (i.e. to 32-33 degrees C) just as a
      consequence of surgical exposure of the artery. Subsequent studies indicated that
      maintaining skull temperature at 37 degrees C compared to 32 degrees C
      significantly (p < 0.05) increased the infarct size following 120 or 160 min
      TMCAO. In other studies, 80 min TMCAO was held constant, but deeper brain
      temperature could be varied by regulating skull temperature at different levels.
      At 36-38 degrees C brain temperature, infarct volumes of 102 +/- 10 to 91 +/- 9
      mm3 occurred following TMCAO. However, at a brain temperature of 34 degrees C, a
      significantly (p < 0.05) reduced infarct volume of 37 +/- 10 mm3 was observed.
      Absolutely no brain infarction was observed if the brain was cooled to 29 degrees
      C during TMCAO. Middle cerebral artery exposure and maintaining brain temperature
      at 37 degrees C without artery occlusion did not produce any cerebral injury.
      These data indicated the importance of controlling brain temperature in cerebral
      ischemia and that reducing brain temperature during ischemia produces a brain
      temperature-related decrease in focal ischemic damage. Brain cooling of 3 degrees
      C and 8 degrees C can provide dramatic and complete, respectively,
      neuroprotection from transient focal ischemia. Multiple mechanisms for reduced
      brain temperature-induced neuroprotection have been identified and include
      reduced metabolic rate and energy depletion, decreased excitatory transmitter
      release, reduced alterations in ion flux, and reduced vascular permeability,
      edema, and blood-brain barrier disruption. Cerebral hypothermia is clearly the
      most potent therapeutic approach to reducing experimental ischemic brain injury
      identified to date, and this is emphasized by the present data which demonstrate
      complete neuroprotection in transient focal stroke. Certainly all available
      information warrants the evaluation of brain cooling for potential implementation
      in the treatment of human stroke.

PMID- 8994208
TI  - Complex roles of glutamate in the Gibbs-Ng model of one-trial aversive learning
      in the new-born chick.
AB  - Glutamate is the most widespread excitatory transmitter in the CNS and is
      probably involved in LTP, a neural phenomenon which may be associated with
      learning and memory formation. Intracerebral injection of large amounts of
      glutamate between 5 min and 2.5 min after passive avoidance learning in young
      chicks inhibits short-term memory, which occurs between 0 and 10 min post
      learning in a three-stage model of memory formation first established by Gibbs
      and Ng(25) [Physiol. Behav. 23:369-375; 1979]. This effect may be attributed to
      non-specific excitation. Blockade of glutamate uptake by L-aspartic and beta
      hydroxamate also abolishes this stage of memory, provided the drug is
      administered within 2.5 min of learning. Interference with either production of
      percursors for transmitter glutamate in astrocytes or with glutamate receptors is
      also detrimental to memory formation, but the effects appear much later. After
      its release from glutamatergic neurons, glutamate is, to a large extent,
      accumulated into astrocytes where it is converted to glutamine, which can be
      returned to glutamatergic neurons and reutilized for synthesis of transmitter
      glutamate, and partly oxidized as a metabolic substrate. The latter process leads
      to a net loss of transmitter glutamate which can be compensated for by de novo
      synthesis of a glutamate precursor alpha-ketoglutarate (alpha KG) in astrocytes,
      a process which is inhibited by the astrocyte-specific toxin fluoroacetate (R. A.
      Swanson, personal communication). Intracerebral injection of this toxin abolishes
      memory during an intermediate stage of memory processing occurring between 20 and
      30 min post-training (50) [Cog. Brain Res, 2:93-102; 1994]. Injection of
      methionine sulfoximine (MSO), a specific inhibitor of glutamine synthetase, which
      interferes with the re-supply of transmitter glutamate to neurons by inhibition
      of glutamine synthesis in astrocytes, has a similar effect. This effect of MSO is
      prevented by intracerebral injection of glutamate, glutamine, or a combination
      and alpha KG and alanine. MSO must be administered before learning, but does not
      interfere with acquisition since short-term memory remains intact. Administration
      of either the NMDA antagonist AP5, the AMPA antagonist DNQX, or the metabotropic
      receptor antagonist MCPF, also induces amnesia. Memory loss in each case does not
      occur until after 70 min post-training, during a protein synthesis-dependent long
      term memory stage which begins at 60 min following learning. However, to be
      effective, AP5 must be administered within 60 s following learning, MCPG before
      15 min post-learning, and DNQX between 15 and 25 min after learning. Together,
      these findings suggest that learning results in an immediate release of
      glutamate, followed by a secondary release of this transmitter at later stages of
      processing of the memory trace, and that one or both of these increases in
      extracellular glutamate concentration are essential for the consolidation of long
      term memory. Since both fluoroacetate and MSO act exclusively on glial cells, the
      findings also show that neuronal-glial interactions are necessary during the
      establishment of memory.

PMID- 8994209
TI  - Parametric changes in response equilibrium during an intra-cranial self
      stimulation (ICSS) task: can reward value be assessed independently of absolute
      threshold?
AB  - Traditional ICSS methodologies have attempted to evaluate changes in the
      rewarding value of brain stimulation by assessing the lowest value of the
      stimulation that will support responding. However, orderly changes in
      suprathreshold indicants of hedonic magnitude such as titration point have been
      shown. In the present experiments, rats were trained to respond on two ICSS
      autotitration schedules in which every response on one lever produced stimulation
      of the medial forebrain bundle, and every Xth response decreased either the
      stimulation current or the stimulation frequency. At any time, a response on a
      second "reset" lever restored the stimulation current or frequency available on
      the stimulation lever to its starting level and operationally defined changes in
      "reward value". In order to study this titration point measure, two response
      requirements (responses/stepdown; step size) and two stimulation parameters
      (initial stimulation level; train duration) were systematically varied. Under
      both current and frequency titration schedules, data indicated that response rate
      and titration point remained stable over repeated trials and multiple testing
      days--parameters being constant. Across all conditions, compared to the frequency
      titration schedule, subjects responding under the current titration schedule
      showed significantly higher titration points and lower rates of responding.
      Indicating the independence of rate and titration point data, parametric
      manipulations did not affect titration point and rate data concurrently. Results
      support the conclusion that titration point is a relative measure of "reward
      value" that is generally independent of response rate, but that is affected by
      manipulations that alter the amount of stimulation available between "resets".
      Additional work is needed in order to determine the relationship between the
      magnitude of stimulation needed to maintain minimal responding and that needed to
      maintain response equilibrium in an autotitration task.

PMID- 8994210
TI  - Effects of MDMA on complex brain function in laboratory animals.
AB  - This review surveys experiments that have examined the effects of acute and
      chronic MDMA exposure on schedule-controlled operant behaviors thought to
      engender responses that reflect the expression of complex brain functions. Such
      functions include time estimation, short-term memory, learning, motivation, and
      color and position discrimination. Recent experiments conducted in the Behavioral
      Toxicology Laboratory at the National Center for Toxicological Research
      concerning MDMA's acute and long-term effects on rhesus monkey performance in an
      operant test battery are compared to previous studies involving the effects of
      MDMA on operant behaviors. Results of these experiments suggest that when given
      acutely, MDMA disrupts complex brain functions associated with learning and time
      estimation more than those associated with short-term memory and visual
      discrimination, and that behavioral tasks requiring relatively high rates of
      responding are particularly sensitive to the disruptive effects of MDMA. Repeated
      exposure to doses of MDMA sufficient to produce long-lasting changes in brain
      neurotransmitter systems results in residual effects (e.g. tolerance,
      sensitivity) on behavioral task performance when subjects are subsequently
      challenged with acute MDMA, whereas baseline (non-challenged) performance of
      these tasks after such exposure generally remains unchanged. Although the
      experiments described herein were conducted on a relatively small number of non
      human subjects, they raise the possibility that long-term effects on cognitive
      processes may also occur in humans exposed to repeated or acute high doses of
      MDMA.

PMID- 8994211
TI  - Neural transplantation as an experimental treatment modality for cerebral
      ischemia.
AB  - Cerebrovascular disease exemplifies the poor regenerative capacity of the CNS.
      While there are methods to prevent cerebral infarction, there is no effective
      therapy available to ameliorate the anatomical, neurochemical and behavioral
      deficits which follow cerebral ischemia. Focal and transient occlusion of the
      middle cerebral artery (MCA) in rodents has been reported to result in
      neuropathology similar to that seen in clinical cerebral ischemia. Using specific
      techniques, this MCA occlusion can result in a well-localized infarct of the
      striatum. This review article will provide data accumulated from animal studies
      using the MCA occlusion technique in rodents to examine whether neural
      transplantation can ameliorate behavioral and morphological deficits associated
      with cerebral infarction. Recent advances in neural transplantation as a
      treatment modality for neurodegenerative disorders such as Parkinson's disease,
      have revealed that fetal tissue transplantation may produce neurobehavioral
      recovery. Accordingly, fetal tissue transplantation may provide a potential
      therapy for cerebral infarction. Preliminary findings in rodents subjected to
      unilateral MCA occlusion, and subsequently transplanted with fetal striatal
      tissue into the infarcted striatum have produced encouraging results.
      Transplanted fetal tissue, assessed immunohistochemically, has been demonstrated
      to survive and integrate with the host tissue, and, more importantly, ameliorate
      the ischemia-related behavioral deficits, at least in the short term. Although,
      this review will focus primarily on cerebral ischemia, characterized by a
      localized CNS lesion within the striatum, it is envisioned that this baseline
      data may be extrapolated and applied to cerebral infarction in other brain areas.

PMID- 8994212
TI  - Participation of noradrenergic pathways in the expression of opiate withdrawal:
      biochemical and pharmacological evidence.
AB  - Several lines of biochemical and pharmacological evidence provide support for the
      involvement of the noradrenergic system in the expression of the somatic symptoms
      of opiate withdrawal. Early studies reported changes in brain noradrenaline and
      metabolite levels during opiate dependence. The significance of these changes has
      been clarified in recent microdialysis studies indicating that acute morphine
      decreases the extraneuronal levels of noradrenaline, whereas an increase in
      release of the neurotransmitter occurs during opiate withdrawal in several brain
      areas. Changes in the sensitivity and density of alpha 2- and beta-adrenoceptors
      have also been reported, probably as a consequence of the decreased presynaptic
      noradrenergic activity induced during morphine dependence. In addition, the
      administration of alpha 2-agonists, such as clonidine, or beta-antagonists, such
      as propranolol, has been reported to attenuate some manifestations of opiate
      withdrawal. The noradrenergic structure mediating the expression of opioid
      abstinence seems to be the locus coeruleus. However, the activation of the locus
      coeruleus during morphine withdrawal seems to be primarily due to the afferent
      projections containing excitatory amino acids and derived from the nucleus
      paragigantocellularis, although intrinsic modifications, consisting of an up
      regulation of the cAMP pathway, seem also to be involved in this activation. The
      participation of the mesolimbic dopaminergic system in opiate dependence and its
      relation with the changes produced in the noradrenergic system are also
      discussed.

PMID- 8994213
TI  - Multiple differences in the play fighting of male and female rats. Implications
      for the causes and functions of play.
AB  - Play fighting is the most commonly occurring form of social play in juvenile
      mammals. Typically, males engage in more play fighting than females, and this
      difference has been shown to depend on the action of androgens perinatally. It is
      generally believed that the differences in play fighting between the sexes are
      quantitative and do not involve qualitative differences in the behavior
      performed. We show that this is an incorrect characterization of sex difference
      in play fighting. For example, in laboratory rats, there are at least five
      different mechanisms that contribute to the observed sex differences in play
      fighting. These mechanisms involve (I) the motivation to initiate play, (II) the
      sensory capacity to detect and respond to a play partner, (III) the organization
      of the motor patterns used to interact with a partner, (IV) age-related changes
      at puberty in initiating play and in responding to playful contact, and (V)
      dominance-related changes in adulthood in the pattern of playful interaction. Sex
      differences in the play fighting of rats are due to an interaction of all of
      these mechanisms, some of which are sex-typical not play-typical, and involve
      both quantitative and qualitative differences. This is clearly different from the
      prevailing view that play fighting is a unitary behavior which is masculinized
      perinatally. Indeed, even though all five mechanisms are androgenized
      perinatally, the sensorimotor differences also involve defeminization (i.e.
      reduction of female-typical qualities). This expanded view of the mechanisms
      contributing to the sex differences in play fighting has implications for both
      the analysis of the neural systems involved, and for the functional significance
      of this activity in childhood and adulthood.

PMID- 8994214
TI  - Cardiac arrest induces decrease of nitric oxide synthase activity and increase of
      free radical generation in rat brain regions.
AB  - Rats were subjected to 15 min cardiac arrest and sacrificed 1 h or 15-20 days
      after resuscitation. Homogenates of brain regions were assayed for nitric oxide
      synthase (NOS) activity (by measuring the mononitrosyl iron complex of NO with
      diethyl dithiocarbamate and endogenous brain Fe2+ using electron spin resonance
      spectroscopy) and generation of free radicals (FRG; by measuring H2O2-induced,
      luminol-dependent chemiluminescence). Cardiac arrest induced marked decrease of
      NOS activity and the increase of FRG, most prominent in cerebellum and less
      marked in cerebral cortex. Two groups of rats were revealed 15-20 days after
      cardiac arrest: with NOS activity significantly lower than control and not
      different from control. Positive linear inter-regional cross-correlations of both
      NOS activity and FRG (except of the group 1 h after resuscitation) as well as
      negative correlations between NOS and FRG were demonstrated.

PMID- 8994215
TI  - Homozygosity at the dopamine D3 receptor gene in schizophrenic patients.
AB  - Dopamine receptors have long been implicated in the etiology of schizophrenia. It
      has been reported an association of schizophrenia with homozygosity at the
      dopamine D3 receptor gene locus. We have investigated the distribution of a D3
      receptor gene polymorphism (BalI) in 107 schizophrenic Spanish patients and 100
      healthy matched controls. No statistically significant differences between the
      patients and control group were detected with respect to either allele
      frequencies or genotype distribution. However, if not corrected for multiple
      testing, a correlation was found between homozygosity and early age of onset of
      schizophrenia (chi 2 = 3.1, df = 1, P = 0.03) and between A1 allele frequency and
      disorganized and undifferentiated schizophrenia (chi 2 = 3.4, df = 1, P = 0.03;
      chi 2 = 2.7, df = 1, P = 0.05, respectively). These results suggest the
      possibility that D3 polymorphisms may be among the physiological factors
      underlying schizophrenia; though not the determining factor.

PMID- 8994216
TI  - Selective blockade of peripheral delta opioid agonist induced antinociception by
      intrathecal administration of delta receptor antisense oligodeoxynucleotide.
AB  - Previous studies have shown that intrathecal (i.t.) administration of antisense,
      but not mismatch, oligodeoxynucleotides (ODNs) to the cloned delta opioid
      receptor (DOR) can inhibit the antinociceptive actions of i.t. delta (delta), but
      not mu (mu) or kappa (kappa), opioid agonists. As a major portion of spinal
      opioid receptors are localized on the central terminals of the small afferent
      fibers, we hypothesized that the effects of antisense ODNs given i.t. might be
      the result of actions at the level of the cell body in the dorsal root ganglion
      (DRG). This possibility was investigated by assessing the antinociceptive actions
      of an i.t. or intrapaw (ipaw) administered mu (morphine), delta ([D-Ala2,
      Glu4]deltorphin) or kappa (CI977) opioid agonist in rats treated with i.t. saline
      or antisense or mismatch ODNs to the DOR (12.5 micrograms, twice-daily for 3
      days). The opioid agonists produced significant antinociception in the 5%
      formalin-flinch test following either i.t. or ipaw administration. DOR antisense
      ODN treatment blocked the antinociceptive actions of both i.t. or ipaw [D-Ala2,
      Glu4]deltorphin without affecting the antinociceptive actions of i.t. or ipaw
      morphine or CI977. Radioligand binding studies with [3H]naltrindole (NTI), a
      delta selective antagonist, indicated an approximate 50% decrease in delta opioid
      receptors in the lumbar spinal cord following i.t. DOR antisense, but not
      mismatch, ODN treatment. DOR antisense or mismatch ODN treatment did not affect
      nu or kappa radioligand binding in lumbar spinal cord. These data suggest the
      possibility that peripheral proteins can be targeted with i.t. antisense ODNs
      providing significant opportunities for the exploration of the physiological and
      pathological significance of these substances.

PMID- 8994217
TI  - Enhanced aggregation of beta-amyloid-containing peptides by extracellular matrix
      and their degradation by the 68 kDa serine protease prepared from human brain.
AB  - To explore whether extracellular matrix components in human brain affect the
      deposition and aggregation of beta-amyloid containing peptides, human brain
      samples from patients with sporadic Alzheimer's disease and normal aged were
      analyzed by Western blot analysis. All major beta-amyloid-containing peptides
      contained epitope(s) which is recognized by anti heparan sulfate antibody.
      Incubation of brain beta-amyloid-containing peptides with human collagen type IV
      in neutral pH efficiently generated a high molecular weight aggregated band,
      approximately 5-fold that of the control sample. We have previously found a
      serine protease which is capable of cleaving an oligopeptide at the N-terminus of
      beta-amyloid. In this study, the protease, which also contains heparan sulfate
      glycoconjugates, degraded the above brain peptides as natural substrates,
      although with different efficiency. These findings suggest that extra-cellular
      matrix components affect the processing and aggregation of beta-amyloid
      containing peptides in human brain.

PMID- 8994218
TI  - Modulation of Ca2+ channels by activation of adenosine A1 receptors in rat
      striatal glutamatergic nerve terminals.
AB  - We determined that activation of adenosine A1 receptors in striatal synaptosomes
      with 100 nM N6-cyclopentyladenosine (CPA) inhibited both the release of
      endogenous glutamate and the increase of intracellular free Ca2+ concentration
      ([Ca2+]i), due to 4-aminopyridine (4-AP) stimulation, by 28 and 19%,
      respectively. Furthermore, CPA enhanced the inhibition of endogenous glutamate
      release due to omega-conotoxin GVIA (omega-Cgtx GVIA), omega-Cgtx MVIIC or omega
      Cgtx GVIA plus omega-Cgtx MVIIC. Similar effects were observed in the [Ca2+]i
      signal. The inhibitory effects of CPA and omega-Cgtx GVIA were additive, but the
      effects of CPA and omega-Cgtx MVIIC were only partially additive. These results
      suggest that P/Q-type Ca2+ channels and other type(s) of Ca2+ channel(s), coupled
      to glutamate release, are inhibited subsequently to activation of adenosine A1
      receptors.

PMID- 8994220
TI  - Lithium decreases turnover of arachidonate in several brain phospholipids.
AB  - In vivo rates of incorporation and turnover of palmitate and arachidonate in
      brain phospholipids were measured in awake rats treated chronically with lithium,
      following intravenous infusion of radiolabeled palmitate and arachidonate,
      respectively. Chronic lithium, at a brain level considered to be therapeutic in
      humans, decreased turnover of arachidonate within brain phosphatidylinositol,
      phosphatidylcholine and phosphatidylethanolamine by up to 80% (P < 0.001). In
      contrast, lithium had a minimal effect on turnover of palmitate, causing only a
      26% reduction in turnover in phosphatidylcholine (P < 0.01). These results
      suggest that a major therapeutic effect of lithium is to reduce turnover
      specifically of arachidonate, possibly by inhibiting phospholipase A2 involved in
      signal transduction. The effect may be secondary to the known action of lithium
      on the phosphoinositide cycle, by inhibiting the activity of inositol
      monophosphatase.

PMID- 8994219
TI  - Corticotropin-releasing factor receptor antagonist infused into the locus
      coeruleus attenuates immobilization stress-induced defensive withdrawal in rats.
AB  - It has been proposed that corticotropin-releasing factor (CRF) released during
      stress in the region of the locus coeruleus (LC) induces changes in behavior that
      are typical indices of anxiety. The experiments tested the ability of a CRF
      antagonist, alpha hCRF9-41, to attenuate stress-induced defensive withdrawal in
      rats. 1 microgram of alpha hCRF in 300 nl was infused bilaterally in the LC of
      rats 10 min prior to 30 min immobilization. The apparatus consisted of a small
      chamber set on one side of a 1 m open field, into which the rat was placed to
      start the test. Restraint induced defensive withdrawal in rats familiar with the
      apparatus and significantly increased latency time to emerge from the chamber,
      total time and mean time spent in the chamber. Infusion of alpha hCRF into the LC
      prior to restraint significantly decreased total and mean time spent in the
      chamber comparing to stressed animals. These results are consistent with
      anatomical, electrophysiological and neurochemical evidence that CRF receptors
      located in, or close to, the LC region influence behaviors induced by stress.

PMID- 8994222
TI  - The contralateral cortex contributes to the effects of hemidecortication on
      neuropeptide Y immunoreactivity in the rat striatum.
AB  - We have previously shown that unilateral lesion by thermocoagulation of sensori
      motor cortex which provides excitatory afferents to the striatum increases the
      number of neuropeptide Y (NPY)-immunoreactive neurons in the rat striatum. The
      present study examined whether this paradoxical effect is due to adaptive
      neuronal mechanisms involving the crossed projections from the contralateral
      spared cortex. To test this hypothesis, we compared the effects of unilateral and
      bilateral cortical lesions on the number of NPY-immunoreactive neurons in the
      striatum. Results showed that animals with bilateral lesion have no significant
      change in NPY immunoreactivity versus control suggesting that the contralateral
      intact cortex is responsible for the increase of NPY-immunoreactive neurons
      detected after unilateral lesion.

PMID- 8994221
TI  - Neurite outgrowth in PC12 cells is enhanced by guanosine through both cAMP
      dependent and -independent mechanisms.
AB  - Extracellular guanosine, guanosine triphosphate (GTP), and 5'-N'
      ethylcarboxamidoadenosine (NECA), each significantly enhanced the proportion of
      nerve growth factor (NGF)-treated rat pheochromocytoma (PC12) cells which had
      neurites, greater than that in cultures exposed to NGF alone. Guanosine and NECA,
      but not GTP, increased intracellular cAMP concentrations. An adenylate cyclase
      inhibitor, SQ22536, completely blocked the cAMP increase induced by both
      guanosine and 0.1 microM NECA. However, SQ22536 only partially blocked guanosine
      enhanced neurite outgrowth, although it completely blocked the neuritogenic
      effect of NECA. Therefore guanosine-enhanced neurite outgrowth through both cAMP
      dependent and -independent mechanisms, while the effect of GTP was cAMP
      independent.

PMID- 8994224
TI  - Enhanced delivery of [125I]glial cell line-derived neurotrophic factor to the rat
      CNS following osmotic blood-brain barrier modification.
AB  - Subsequent to osmotic (mannitol-induced) blood-brain barrier (BBB) opening,
      [125I]glial cell line-derived neurotrophic factor (GDNF) was detected throughout
      the ventricular system, associated with the ependymal cell layer and
      extracellular matrix and to some extent penetrated into the cerebral cortex,
      subcortical gray matter, substantia nigra, septum, eye and optic nerve at 1 and
      24 h following an intracarotid administration. Our study indicates that osmotic
      opening of the BBB allows for extensive distribution of GDNF throughout the
      central nervous system (CNS).

PMID- 8994223
TI  - Cloning of the 3' end of rat bax-alpha and corresponding developmental down
      regulation in differentiating primary, cultured oligodendrocytes.
AB  - Bax-alpha is thought to form heterodimers with Bcl-2 and prevent apoptotic cell
      death. A sequence was isolated from oligodendrocyte cDNA corresponding to the
      uncloned 3' end of the rat bax-alpha coding region and part of the 3' UTR via a
      degenerate polymerase chain reaction (PCR)-based cloning method. The rat bax
      alpha clone is 96 and 91% homologous to mouse and human clones, respectively, and
      the 3' UTR demonstrates high homology with the cloned human 3' UTR. Northern
      analysis demonstrated that the 1.0 kb bax-alpha mRNA species was predominant. bax
      alpha mRNA is expressed in mitotic, oligodendrocyte progenitors, and is
      subsequently down-regulated 2-fold in differentiating oligodendrocytes.

PMID- 8994225
TI  - Expression of Fos-like immunoreactivity in the brain of quail chick emitting the
      isolation-induced distress calls.
AB  - The social isolation intensively induces distress call in neonatal chicks of
      Japanese quail. The brain regions activated during the isolation were mapped
      using immunocytochemical detection of c-Fos (the product of immediate early gene
      c-fos). Fos-like immunoreactivity was observed in a variety of brain regions in
      isolated chicks that had emitted distress calls. The density of Fos-positive
      cells in dorso-medial mesencephalic areas (including the intercollicular nucleus
      and the central gray) was much higher than those of control animals that were
      kept in groups and emitted very few or no distress calls, whereas the
      distribution partially overlapped in isolated and control animals. These data, in
      addition to our lesion and stimulation studies, provide anatomical support for
      the involvement of the mesencephalic regions in generating distress calls during
      social isolation.

PMID- 8994226
TI  - The soluble form of Fas molecule is elevated in parkinsonian brain tissues.
AB  - Fas is an apoptosis-signaling receptor molecule on the surface of a number of
      cell types. The soluble form of Fas (sFas) was measured for the first time in
      brain (caudate nucleus, putamen and cerebral cortex), ventricular cerebrospinal
      fluid (VCSF), and lumbar CSF (LCSF) from control and parkinsonian patients by a
      highly sensitive two-site sandwich enzyme-linked immunosorbent assay (ELISA). The
      concentrations of sFas in nigro-striatal dopaminergic regions were significantly
      higher in parkinsonian patients than those in controls, whereas this product in
      cerebral cortex showed no significant difference between parkinsonian and control
      subjects. Neither VCSF nor LCSF contained the sFas molecule in the detectable
      amounts (< 16 pg/ml). These results suggest that the presence of sFas possibly
      leads to cell death/neurodegeneration in parkinsonian brain.

PMID- 8994227
TI  - Methylcobalamin induces a long-lasting enhancement of the field potential in rat
      suprachiasmatic nucleus slices.
AB  - Optic nerve stimulation has been reported to evoke a field potential (FP) in rat
      suprachiasmatic nucleus (SCN) slices. Methylcobalamin,delta-(5,6
      dymethylbenzimidazolyl)-Co-methyl-cobam ide (Me-B12) enhanced this FP and the
      enhancement lasted more than 1 h after washing out. Maximal enhancement (143.6 +/
      9.8%) was achieved at a concentration of 10 microM. By contrast, cyanocobalamin
      containing CN- instead of CH3- showed no enhancement of the amplitude in the FP.
      Me-B12 induced enhancement of FP was strongly blocked by an N-methyl-D-aspartate
      (NMDA) receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV). These
      results indicate that CH3- in the Me-B12 is required to modulate the FP amplitude
      and the NMDA receptor is involved in the long-lasting FP enhancement induced by
      Me-B12. The present results suggest that Me-B12 modifies the photic entrainment
      of the circadian clock in the suprachiasmatic nucleus via an activation of NMDA
      receptors.

PMID- 8994228
TI  - Brain-derived neurotrophic factor reduces necrotic zone and supports neuronal
      survival after spinal cord hemisection in adult rats.
AB  - Spinal cord injury (SCI) often results in necrotic changes leading to cavity
      formation and glial scar tissue in the lesion zone. We have examined the effects
      of continuous topical administration of brain-derived neurotrophic factor (BDNF)
      on cavity formation and neuronal death after SCI. Following retrograde
      prelabeling of the tibial motoneurons in the L4-L6 spinal cord segments with the
      fluorescent dye Fast blue, a spinal hemisection was performed in the L5 segment.
      At 4 weeks postoperatively, only 66% of the labeled motoneurons remained in the
      untreated animals, while BDNF treatment resulted in a significant reduction in
      size of the lesion cavity and 92% motoneuron survival. A therapeutic potential of
      BDNF in the early treatment of SCI is suggested.

PMID- 8994229
TI  - alpha-Tocopherol attenuates alcohol-induced cerebral vascular damage in rats:
      possible role of oxidants in alcohol brain pathology and stroke.
AB  - Effects of chronic (14 day) pretreatment of timed-release of alpha-tocopherol
      (approximately 1.25-5 mg/day) on alcohol-induced venular cerebrovasospasm,
      microvessel rupture and micro-hemorrhaging was studied by direct, quantitative in
      vivo high-resolution TV microscopy of the intact rat brain. Sham animals
      chronically treated with placebo exhibited concentration-dependent venular
      cerebrovasospasm, microvessel rupture and focal hemorrhages, irrespective of
      route (i.e. perivascular, systemic) of ethanol administration. alpha-Tocopherol
      pretreatment either prevented or ameliorated greatly the cerebrovasospasm and
      vascular damage induced by ethanol. These results suggest that alcohol-induced
      cerebral vascular and brain damage by reperfusion injury events triggers lipid
      peroxidation of vascular smooth muscle and endothelial cell membranes; these pro
      oxidant events could play a crucial role in the pathogenesis of alcohol-induced
      cerebral ischemia and stroke.

PMID- 8994230
TI  - Transient patterns of calbindin-D28k expression in the developing striatum of
      man.
AB  - In fetal and adult human brains, calbindin immunoreactivity (CB-ir) of
      neostriatal neuropil showed inhomogeneous pattern. A mosaic of CB-ir neuropil
      patches matching the acetylcholinesterase (AChE)-reactive patches and most of the
      encapsulated cell-dense islands was distributed in a lighter stained background
      matrix. During infancy, the pattern of CB expression changed from one of CB-rich
      patches to one of CB-poor striosomes and rich matrix. Furthermore, we observed a
      steady development of population of medium-sized neurons in the striatal matrix;
      in addition, a transient CB-expression was found in cells of the ganglionic
      eminence and presumably in a subset of striatal interneurons.

PMID- 8994231
TI  - Apomorphine-induced suppression of prey oriented turning in toads is correlated
      with activity changes in pretectum and tectum: [14C]2DG studies and single cell
      recordings.
AB  - In common toads, after systemic administration of the dopamine agonist
      apomorphine (APO), prey-oriented turning was suppressed. Searching for neural
      correlates, the present study shows APO-induced increases in glucose utilization
      in the retinorecipient pretectum and dorsal optic tectum and a decrease in the
      medial tectal output layers. This pattern of metabolic activity is resembled by
      neuronal discharge activities recorded in response to a prey stimulus; the
      discharge rates are increased in retinal ganglion cells and pretectal neurons and
      decreased in tectal output neurons. We suggest that an APO-induced enhancement of
      pretecto-tectal inhibitory influences contributes to the reduction of tectal
      output, thus suppressing prey-oriented turning behavior.

PMID- 8994232
TI  - Can improved diet contribute to the prevention of cataract?
AB  - British adults who were disabled by defective vision were estimated to number
      1.668 million in 1988. Cataract is a most important cause of disability and
      blindness. Cataract develops earlier in life in populations with low income and
      inferior education. Cataract was shown to be associated with riboflavin
      deficiency in animals in the 1930s and subsequently with deficiencies of amino
      acids, vitamins and some minerals. In Britain and the U.S.A. there is a
      substantial spread in the intake of these micronutrients, the antioxidants and B
      vitamins, which have been shown to have low intakes in patients at higher risk of
      cataract. But there is little reliable information on the comparative importance
      of different micronutrients in Britain and longitudinal surveys relating diet to
      progression of cataract are recommended, which should also include non-nutrient
      risk factors for cataract such as smoking, medication and industrial chemicals.

PMID- 8994233
TI  - Why do we weigh infants and children?

PMID- 8994234
TI  - Occurrence of nitrate, nitrite and volatile nitrosamines in certain feedstuffs
      and animal products.
AB  - Nitrate, nitrite and nitrosamines were analysed in poultry feeds, meat and eggs.
      The poultry meat was boiled and roasted while the eggs were raw and boiled, and
      the effects of these processing treatments on the level of these compounds were
      investigated. Nitrate levels in the meat samples were significantly (P < 0.05)
      reduced by boiling and roasting, with boiling being more effective. Nitrite
      levels were also reduced significantly by processing (P < 0.05). The feed samples
      contained levels of nitrate which were significantly different (P < 0.05) from
      one producer to another. Nitrite levels were generally low in all feed samples.
      Nitrosamines were not detected in any of the feed samples and in the meat samples
      except in two samples of boiled meat which contained 0.001 g/kg each.

PMID- 8994235
TI  - Maternal education, breastfeeding behaviours and lactational amenorrhoea: studies
      among two ethnic communities in Ile Ife, Nigeria.
AB  - Breastfeeding is an important child survival strategy. This report aims to
      describe the unique contributions of education, ethnicity, and other variables to
      breastfeeding outcomes. The study was conducted among two groups of lactating
      mothers in Ile Ife, southwestern Nigeria, using structured questionnaires
      focusing on their breastfeeding history and current practice. Breastfeeding
      initiation was delayed in both groups, and primary education is the most
      significant predictor of initiation of breastfeeding within 6 hours of delivery
      (OR = 3.92, p = 0.0117). Breastfeeding duration (SD) was 13.7 (4.3) months for
      the Yorubas and 17.5 (3.4) for the Hausas. Its only significant predictors are
      education (p < = 0.0001), with an average decrease in breastfeeding duration of
      3.2 and 6.6 months with mother's education to the primary and post-primary levels
      respectively, compared with mothers with no education. In turn, breastfeeding
      duration is the most significant predictor of the duration of lactational
      amenorrhoea (p = 0.0000). Mothers with some formal education are also more likely
      to start feeding human milk substitutes at 2 weeks (OR = 3.83, p = 0.024). The
      most important variable determining breastfeeding in this study is education. The
      educated mother is more likely to be involved in economic activity away from the
      home. To protect breastfeeding in these communities, there is a need for
      programmes to support the breastfeeding mother who works.

PMID- 8994236
TI  - Prevention of nutrient loss during preparation of the most popular weaning diet
      in Nigeria--practical considerations.
AB  - A pilot study is presented as an attempt to modify the traditional method of
      preparing maize gruel 'ogi', the most popular weaning diet in Nigeria. The
      modification consists of completely grinding the food to a fine paste without
      sieving. Cooked samples of the unsieved maize gruel were taken for proximate
      chemical analysis and organoleptical evaluation. Analysis revealed that protein,
      fat and mineral losses in the unsieved maize gruel were much less. The majority
      (58%) of mothers of malnourished children rated the cooked modified maize gruel
      favourably and the overall acceptability was positively rated by 61%. The
      inference to be drawn is that through food demonstrations and nutritional health
      information at the nursing mothers' level, the traditional method of preparing
      the most popular weaning diet in Nigeria can be modified to advantage.

PMID- 8994237
TI  - Consequences, cultural factors, detection, and prevention of HIV/AIDS in sub
      Saharan Africa.

PMID- 8994238
TI  - Cervical pregnancy: past and future.
AB  - Cervical pregnancy (CP) is a rare life-threatening form of ectopic pregnancy
      occurring in 1 of 8628 deliveries. We reviewed 117 cases of CP in the English
      language literature from 1978 and added three cases from our department. Etiology
      of CP is still unknown, but there is evidence for its association with
      cervicouterine instrumentation. The possible role of embryo chromosomal
      abnormality in the CP etiology is considered. Sonography improved pretreatment
      diagnosis up to 81.8 percent. Obligatory sonographic criteria of CP include
      endocervical localization of the gestational sac and trophoblastic invasion.
      About 60 percent of cervical pregnancies are with a viable fetus. The majority of
      patients with a cervical pregnancy are women with low parity, thus, the current
      treatment trend is to preserve their reproductive function. The main problem of
      conservative treatment is life-threatening hemorrhage after pregnancy evacuation.
      The use of cervical canal tamponade with a Foley catheter balloon led to reliable
      hemostasis in 92.3 percent of cases in which this method was used. Early
      diagnosis of CP allowed for treatment by chemotherapy in 32 cases, with an 81.3
      percent success rate. Serial beta-human chorionic gonadotropin levels and
      transvaginal ultrasound with color Doppler are used to monitor therapy. Another
      conservative treatment modality is local intrasac KCI injections. Hysterectomy is
      recommended mostly for second and third trimester cervical pregnancy, or for
      uncontrolled bleeding.

PMID- 8994239
TI  - Venous thromboembolism during pregnancy: a current review of diagnosis and
      management.
AB  - Pregnancy is widely recognized to be a physiologic state with a markedly elevated
      risk for thromboembolic complications. The diagnosis and management of venous
      thromboembolic events during pregnancy, however, remains controversial because of
      the lack of prospective, randomized trials that have included pregnant women.
      Significant progress has been made in the last 10 years in the management of
      these conditions in the nonpregnant patient and strong clinical guidelines have
      been established recently. Obstetrician-gynecologists may modify these guidelines
      and apply them to the pregnant patient based on their knowledge of the
      physiologic changes in pregnancy. Objective diagnostic techniques should be used
      liberally when the diagnosis of deep vein thrombosis or pulmonary emboli is
      considered because early intervention may prevent serious maternal sequelae
      including death. Heparin remains the anticoagulant of choice during pregnancy
      because of its proven safety for both the patient and the fetus. It is likely
      that long-term anticoagulation is necessary when venous thromboembolism occurs
      antepartum, although the most efficacious regimen has yet to be established.
      There is some concern about the prolonged use of heparin during pregnancy,
      particularly regarding the risk of osteopenia.

PMID- 8994240
TI  - Relevance of molecular medicine to clinical obstetrics and gynecology.
AB  - Understanding molecular biology can improve the clinical acumen of the practicing
      obstetrician/gynecologist. An area of basic research now becoming clinically
      relevant involves the G proteins and G protein-coupled receptors. Clinicians
      already manipulate G protein-coupled receptors in their daily practice. Examples
      include the administration of oxytocin (oxytocin receptors), beta-2 tocolytic
      agents (beta 2-adrenergic receptors), GnRH agonists (GnRH receptors), exogenous
      gonadotropins (FSH and LH receptors), and bromocriptine (dopamine receptor).
      Clinically important disorders presenting to the obstetrician/gynecologist
      include some forms of precocious puberty, delayed puberty, premature ovarian
      failure, and pituitary adenomas which are due to mutations of G proteins and G
      protein-coupled receptors. The importance of these proteins is demonstrated by
      the fact that G protein-related genes comprise about 1 percent of the human
      genome. Additionally, the knowledge that some G protein gene mutations are
      present in the germ line, and others are somatic cell in origin (and not
      heritable), aids in more accurate genetic counseling to patients.

PMID- 8994241
TI  - Culture of fetal erythroid progenitor cells from maternal blood for non-invasive
      prenatal genetic diagnosis.
AB  - Fetal committed erythroid progenitors CFU-E and M-BFU-E released into the
      maternal circulation during pregnancy are ideal candidates for in vitro
      proliferation since their lifespan is short and they can form colonies of 100
      1000 cells in a semi-solid medium. In order to propagate these cells with a high
      rate of purity, a strategy was devised based on their prior enrichment with
      biotin-labelled human erythropoietin ligand and magnetic sorting before culturing
      in a suitable medium. Eight euploid pregnancies investigated in order to address
      this issue produced fetal clones in cultures with 18 per cent purity as assessed
      by polymerase chain reaction (PCR) analysis for Y-specific sequences,
      immunocytochemical staining for fetal gamma-globin, and fluorescence in situ
      hybridization (FISH) study. The CFU-E-type colony was the most represented
      progenitor, followed by M-BFU-E, and only occasionally was the detection of CFU
      GEMM recorded. The retrospective diagnosis of two cases of fetal Down's syndrome
      by culturing fetal cells from maternal blood was accomplished for the first time.
      FISH analysis disclosed a strong presence of fetal trisomic cells (70 per cent
      and 40 per cent in the two cases). This strong presence would suggest a
      preferential leakage into maternal blood. The overall results of this study
      demonstrate that fetal cells can be cultured in vitro with reliable
      reproducibility, thus making the prospect of a non-invasive prenatal genetic
      diagnosis realistic.

PMID- 8994242
TI  - Activity of the antioxidant enzymes superoxide dismutase and glutathione
      peroxidase in fetal erythrocytes.
AB  - It is generally accepted that the balance between the formation and inactivation
      of reactive oxygen species may be abolished within the perinatal period, as a
      consequence of rapid changes in tissue oxygen concentration and the development
      of antioxidant defence enzyme activities. We studied the ontogeny of the
      antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx)
      in fetal blood samples. The activity of SOD in fetal erythrocytes taken in the
      17th gestational week was the same as that in erythrocytes of healthy blood
      donors. On the other hand, GPx activity was significantly lower between the 17th
      and 25th gestational week and at the time of delivery, compared with the healthy
      adult control. Our results suggest that the supposed underdevelopment of the
      antioxidant system in the lungs or in the other organs of premature infants
      cannot be monitored by SOD and GPx activities in erythrocytes, because these
      reach adult levels before the 17th week for SOD and from the 26th to the 35th
      gestational week for GPx, with lower levels from the 17th to the 25th week and at
      term.

PMID- 8994243
TI  - In fetuses with isolated hydronephrosis, urinary beta 2-microglobulin and N
      acetyl-beta-D-glucosaminidase (NAG) have a limited role in the prediction of
      postnatal renal function.
AB  - Seventy-one fetal urine samples were taken from the bladder or renal pelvis of 33
      fetuses at 13-36 weeks' gestation with a diagnosis of urinary tract anomaly.
      Severe isolated hydronephrosis in the absence of an enlarged bladder was the
      indication for sampling in 12/33 fetuses (26 samples), who were retrospectively
      classified into three groups: normal, intermediate, and dysplastic, based on the
      evaluation of postnatal renal function or histology. For all samples, urinary
      sodium (Na+), calcium (Ca2+), creatinine, beta 2-microglobulin, and N-acetyl-beta
      D-glucosaminidase (NAG) were measured. Among the 71 fetal urine samples, both
      beta 2-microglobulin and NAG correlated inversely with gestational age, Na+, and
      Ca2+, but not with creatinine concentrations. However, the correlation of urinary
      beta 2-microglobulin with gestational age was dependent on the Na+ and Ca2+
      concentrations, whereas urinary NAG correlated significantly with urinary Na+ and
      Ca2+, and also with gestational age. In fetuses with isolated hydronephrosis,
      only Na+, and not Ca2+, was significantly related to both beta 2-microglobulin
      and NAG. Only Na+ and beta 2-microglobulin were significantly, and similarly,
      higher in both dysplastic and intermediate kidneys when compared with fetuses
      with normal postnatal function. If only the last urine sampled was considered,
      there was overlapping of all parameters in the three groups. In isolated
      hydronephrosis, only the most extreme forms of renal failure might be suggested
      by elevated levels of Na+, Ca2+, beta 2-microglobulin, and NAG, without an
      obvious superiority of any of these parameters.

PMID- 8994244
TI  - Combining inhibin A with existing second-trimester markers in maternal serum
      screening for Down's syndrome.
AB  - To assess the value of inhibin A as an additional second-trimester maternal serum
      marker of Down's syndrome we studied 56 affected and 280 unaffected pregnancies
      matched for gestational age. The median level in the cases was 1.62 multiples of
      the gestation-specific median (MOM) in the controls, with 95 per cent confidence
      limits of 1.34-1.96. The distribution of inhibin levels in affected and
      unaffected pregnancies was approximately log Gaussian, with means about 1
      standard deviation apart. This degree of separation was similar to that for human
      chorionic gonadotropin (hCG), free beta-hCG, and unconjugated oestriol (uE3), but
      about double that of alpha-fetoprotein (AFP) measured in the same samples.
      Inhibin was largely uncorrelated with AFP and uE3, whereas the log correlation
      coefficient with hCG was 0.29 (P = 0.19) for Down's syndrome and 0.41 (P <
      0.0001) for unaffected pregnancies; with free beta-hCG, it was 0.18 (P = 0.38)
      and 0.38 (P < 0.0001), respectively. On the basis of these results and other
      published studies, we estimate that measuring inhibin A in addition to AFP and
      hCG or free beta-hCG (with or without uE3) will increase the detection rate for a
      fixed 5 per cent false-positive rate by about 7 per cent.

PMID- 8994245
TI  - Second-trimester dimeric inhibin-A in Down's syndrome screening.
AB  - Initial studies of immunoreactive inhibin using a commercial assay have shown
      levels to be increased in three second-trimester series of maternal samples from
      Down's syndrome-affected pregnancies. This assay detected non-specifically all
      forms of circulating inhibin, dimeric and free alpha subunits, whether fully or
      partially processed. More recently, a new specific assay for dimeric inhibin-A
      has shown elevated results in both a first-trimester and a second-trimester
      series of cases. In order to assess the value of dimeric inhibin-A as a potential
      marker in the second trimester, we have analysed 157 Down's syndrome cases and
      used 367 unaffected cases across the gestational range 14-20 weeks to establish
      control medians and population parameters. In our series, the median MOM in
      Down's cases was 1.77, significantly higher than in the controls. At a 5 per cent
      false-positive rate, dimeric inhibin-A alone identified 37 per cent of cases.
      When used in conjunction with maternal age and other marker combinations,
      mathematical modelling showed detection rates rising from 48 per cent (inhibin-A
      plus age) to 61 per cent (inhibin-A, free beta hCG, age) and 68 per cent (inhibin
      A, AFP, free beta hCG, age). Our data suggest that dimeric inhibin-A may have
      greater potential earlier in gestation when median levels at 14-16 weeks are 1.92
      compared with 1.46 at 17-23 weeks. Dimeric inhibin-A may be a valuable addition
      to screening protocols, particularly in early gestations.

PMID- 8994246
TI  - Down's syndrome screening marker levels following assisted reproduction.
AB  - Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and
      unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation
      induction and 327 who had in vitro fertilization. There was a highly
      statistically significant increase in hCG and reduction in uE3 among those with
      ovulation induction. The median levels were respectively 1.09 and 0.92 multiples
      of the normal gestation-specific median (MOM) based on a total of 34582 women.
      Ovulation induction appeared to have no material effect on the median AFP level
      but this masked a significant increase when treatment was with Clomiphene (1.05
      MOM) and a significant decrease when Pergonal was used (0.93 MOM). There was a
      highly statistically significant reduction in uE3 among women having in vitro
      fertilization with a median level of 0.92 MOM. Those fertilized with a donor egg
      (21) had significantly higher AFP and uE3 levels than when their own egg was
      used. Our results were confounded by differences in gravidity, but formally
      allowing for this factor did not materially change the findings. None of the
      observed effects is great enough to warrant routine adjustment of marker levels
      to allow for them. Moreover, women with positive Down's syndrome screening
      results can be reassured that this is unlikely to be due to them having had
      assisted reproduction.

PMID- 8994247
TI  - Refinements in managing maternal weight adjustment for interpreting prenatal
      screening results.
AB  - This study examines the relationship between maternal weight and serum levels of
      alpha-fetoprotein, unconjugated oestriol, and human chorionic gonadotropin in a
      population of 47,585 women being provided with prenatal screening for Down's
      syndrome and open neural tube defects. The study population contains sufficient
      numbers of women at the extremes of weight to allow the determination that a
      reciprocal-linear equation more accurately describes the weight relationship for
      two of the three analytes than the currently used log-linear equations. The
      reciprocal-linear equations, while more appropriate, provide only a minimal
      advantage over the log-linear equations. A more important finding is that
      published weight equations may not be optimal for some screening programmes, due
      to differences in the mean weight of the populations being tested. Screening
      programmes are encouraged to calculate their own weight correction formulae,
      based on data from their own population, and to monitor the mean maternal weight
      to detect when modifications in the weight correction formulae might be
      indicated.

PMID- 8994248
TI  - Early filtration amniocentesis for further investigation of mosaicism diagnosed
      by chorionic villus sampling.
AB  - In 44 pregnancies where chorionic villus sampling (CVS) had shown mosaicism,
      early amniocentesis using a filter technique was carried out with the purpose of
      clarifying the fetal karyotype and reducing the waiting time for a final
      karyotype. Since the filter technique increases the cell yield of the amniotic
      fluid sample, it was hypothesized that this technique could be applied as soon as
      the mosaic CVS result was available, without compromising the culturing of the
      amniotic fluid cells. The mean gestational age at amniocentesis was 12.5 weeks
      and the mean gestational age at the time of the final karyotype was 13.9 weeks.
      All amniotic fluid sampling procedures and cultures were successful. Four
      pregnancies were terminated due to abnormal karyotypes (9.1 per cent). Two
      spontaneous abortions occurred in the second trimester (5.0 per cent), and one
      infant was lost at term due to unexplained intrapartum death. The total fetal
      loss rate was 7.5 per cent. This loss rate is concordant with other reported
      series where the outcome of pregnancies with placental mosaicism has been
      evaluated. We conclude that early amniocentesis with the filtration technique is
      a useful method for follow-up on CVS, mosaicism, providing results prior to 14
      weeks of gestation.

PMID- 8994249
TI  - Maternal serum testing for alpha-fetoprotein and human chorionic gonadotropin in
      high-risk pregnancies.
AB  - To evaluate the variations and potential clinical use of serial maternal alpha
      fetoprotein (AFP) and human chorionic gonadotropin (hCG) in pregnancies at risk
      of pregnancy-induced hypertension (PIH) and/or intrauterine growth retardation
      (IUGR), we investigated the relationship between placental sonographic findings,
      uterine artery Doppler measurements, and maternal serum AFP, hCG, and uric acid
      levels between 20 and 34 weeks of pregnancy. Maternal serum samples were
      collected from 41 singleton pregnancies with bilateral uterine notches and/or an
      increased uterine artery pulsatility index at 20-24 weeks. Maternal serum AFP,
      intact hCG and free alpha and beta subunits, and uric acid circulating levels
      were measured in all cases at 20-24 weeks and 25-28 weeks. Placental sonographic
      investigations comprised measurements of thickness and morphology. Twenty
      pregnancies had a normal outcome and 21 had an adverse outcome, including eight
      complicated by severe PIH with fetal IUGR, eight by isolated IUGR, three by mild
      PIH with normal fetal growth, and two by placental abruption. At the time of the
      first scan, the placental thickness and maternal serum levels of AFP, hCG, and
      uric acid were significantly increased in pregnancies with adverse outcomes,
      compared with those with a normal outcome. In subsequent maternal serum
      examinations, the incidence of elevated hormonal levels fell for AFP, intact hCG,
      and beta-hCG, whereas it increased for the uric acid level. No difference was
      found at any stage for the alpha-hCG level. Seven out of 11 pregnancies
      complicated by PIH presented with elevated MSAFP and MShCG and a large
      heterogeneous placenta at the first visit, whereas no pregnancy with a normal
      outcome presented with similar features. This study has shown a significant
      association between abnormal development of the utero-placental circulation,
      elevated MSAFP and MShCG at mid-gestation, and subsequent adverse pregnancy
      outcome. Serial measurements of MSAFP and MShCG do not provide extra information
      for the follow-up of these pregnancies.

PMID- 8994250
TI  - Prenatal diagnosis of supernumerary der(22)t(11;22) associated with the Dandy
      Walker malformation in a fetus.
AB  - We present the first report of prenatally diagnosed Dandy-Walker malformation
      with the karyotype of partial trisomy 11 and 22 due to familial translocation
      t(11;22)(q23;q11) inherited in three generations. We demonstrate that the Dandy
      Walker malformation can be an associated congenital malformation of supernumerary
      der(22)t(11;22) syndrome and emphasize the importance of chromosomal analysis and
      genetic counselling in the obstetric management of prenatally diagnosed Dandy
      Walker malformation.

PMID- 8994251
TI  - The sonographic finding of persistent umbilical cord cystic masses is associated
      with lethal aneuploidy and/or congenital anomalies.
AB  - Advancements in sonographic technology have led to improved prenatal detection of
      fetal anomalies. Umbilical cord cystic masses are being detected prenatally and
      several case reports have appeared in the literature. We report three new cases
      in which umbilical cord cystic masses were detected prenatally; two cases in the
      later half of pregnancy and one case in the first trimester. The literature was
      reviewed and summaries of the 23 reported cases of persistent second- and third
      trimester umbilical cord cystic masses and their implications are discussed.
      There is a high association (18 of 23 cases) with lethal chromosomal anomalies
      and/or congenital malformations suggesting that the finding of an isolated
      umbilical cord cystic mass should lead to further detailed sonographic
      evaluation.

PMID- 8994252
TI  - Prenatal sonographic diagnosis of congenital varicella infection--a case report.
AB  - We report a case of fetal varicella infection following the diagnosis of maternal
      varicella infection at 13 weeks of pregnancy. Anomalies noted sonographically at
      26 weeks' gestation included oligohydramnios, symmetrically impaired fetal
      growth, limb anomalies, a thin placenta, and widespread dystrophic calcification
      of the abdominal cavity and chest, including the lungs and myocardium. Some of
      these sonographic anomalies have been reported previously. However, to our
      knowledge, prenatal diagnosis of calcification of the lungs and myocardium has
      not been described.

PMID- 8994253
TI  - Severe fetomaternal alloimmune thrombocytopenia presenting with fetal
      hydrocephalus.
AB  - We report two patients where the finding of isolated fetal hydrocephalus led to
      the detection of severe fetal thrombocytopenia, using fetal blood sampling.
      Serological investigation led to the diagnosis of fetomaternal alloimmune
      thrombocytopenia (FMAIT) due to anti-HPA-1a. Both women had had previous
      unsuccessful pregnancies probably due to FMAIT; one had had four miscarriages at
      17-18 weeks' gestation. The other had had one previous pregnancy complicated by
      severe fetal anaemia, and eventually hydrocephalus developed and the fetus died
      without the diagnosis of FMAIT being considered. Subsequent pregnancies in the
      two women were also affected by FMAIT, but prenatal treatment, predominantly with
      serial fetal platelet transfusions, resulted in a successful outcome in both
      cases. These observations suggest that FMAIT should be suspected if there is
      isolated fetal hydrocephalus, unexplained fetal anaemia, or recurrent
      miscarriages. The accurate diagnosis of FMAIT is important because recent
      advances in prenatal management can improve the outcome of subsequently affected
      pregnancies.

PMID- 8994254
TI  - i(18q) in amniotic and fetal cells with a normal karyotype in direct chorionic
      villus sampling: cytogenetics and pathology.
AB  - A case of false-negative discrepancy between results of chorionic villi (direct
      preparation) and those of fetal tissue with an isochromosome 18q [i(18q)] in
      amniotic cells and fetal blood is reported. Fluorescence in situ hybridization
      (FISH) confirmed this uncommon chromosomal rearrangement. The fetus showed
      cyclopia and multiple congenital anomalies which have never been reported in
      cases of i(18q).

PMID- 8994255
TI  - Similarities in women's decision-making in the U.S. and U.K. during prenatal
      screening for Down's syndrome.

PMID- 8994256
TI  - Current awareness in prenatal diagnosis.

PMID- 8994257
TI  - Cytoplasmic fate of messenger RNA. Introduction.

PMID- 8994258
TI  - TOP genes: a translationally controlled class of genes including those coding for
      ribosomal proteins.

PMID- 8994259
TI  - RNase L: effector nuclease of an activatable RNA degradation system in mammals.

PMID- 8994260
TI  - 3' untranslated regions of c-myc and c-fos mRNAs: multifunctional elements
      regulating mRNA translation, degradation and subcellular localization.

PMID- 8994261
TI  - Cell-free systems for analysis of cytoplasmic mRNA turnover.

PMID- 8994262
TI  - Mechanisms for posttranscriptional regulation by iron-responsive elements and
      iron regulatory proteins.

PMID- 8994263
TI  - Interaction between iron-regulatory proteins and their RNA target sequences, iron
      responsive elements.
AB  - In this chapter, we have focused on the biochemistry of IRP-1 and the features
      which distinguish it from the related RNA-binding protein, IRP-2. IRP-1 is the
      cytoplasmic isoform of the enzyme aconitase, and, depending on iron status, may
      switch between enzymatic and RNA-binding activities. IRP-1 and IRP-2 are trans
      acting regulators of mRNAs involved in iron uptake, storage and utilisation. The
      finding of an IRE in the citric acid cycle enzymes, mitochondrial aconitase and
      succinate dehydrogenase, suggests that the IRPs may also influence cellular
      energy production. These two proteins appear to bind RNAs with different but
      overlapping specificity, suggesting that they may regulate the stability or
      translation of as yet undefined mRNA targets, possibly extending their regulatory
      function beyond that of iron homeostasis. The interaction between the IRPs and
      the IRE represents one of the best characterised model systems for
      posttranscriptional gene control, and given that each IRP can also recognise its
      own unique set of RNAs, the search for new in vivo mRNA targets is expected to
      provide yet more surprises and insights into the fate of cytoplasmic mRNAs.

PMID- 8994264
TI  - Cytoplasmic fate of eukaryotic mRNA: identification and characterization of AU
      binding proteins.

PMID- 8994265
TI  - Translational control by polyadenylation during early development.

PMID- 8994266
TI  - Function and characterization of poly(A)-specific 3' exoribonucleases.

PMID- 8994267
TI  - The Wolf Man's analysis--an interactional perspective.

PMID- 8994268
TI  - Mental imagery in the organization and transformation of the self.

PMID- 8994269
TI  - Repetitive dreams and the central masturbation fantasy.

PMID- 8994270
TI  - The healing presence: Part I. The witness as self-object function.

PMID- 8994271
TI  - Fictionalism and psychoanalyzed history.

PMID- 8994272
TI  - Anatomy of soul murder: family romance and structure of delusion in the memoirs
      of D.P. Schreber, Part I.

PMID- 8994273
TI  - Faith is a telescope: the ritualization of vision in the early life of Ralph
      Waldo Emerson.

PMID- 8994274
TI  - Therapist-patient sexual contact.

PMID- 8994275
TI  - The consistency of DSM-III-R delusional disorder in a first-admission sample.
AB  - The temporal consistency of the research diagnosis of DSM-III-R delusional
      disorder was assessed. Subsequent to their first psychiatric hospitalization,
      psychotic patients were diagnosed twice using a best-estimate procedure after 6-
      and 24-month follow-up. Only 57.1% of the 7 subjects diagnosed at the 6-month
      follow-up conference retained the diagnosis at the 24-month review. Conversely,
      50.0% of the 8 subjects given this diagnosis at 24 months had different 6-month
      diagnoses. By contrast, 100% of a matched control group maintained the same
      diagnosis at both time points. Course and outcome in this sample varied
      considerably, with 2 of the subjects making severe suicide attempts. Longitudinal
      assessment in psychotic patients in their first episode is mandatory, and an
      initial diagnosis of delusional disorder has to be interpreted as provisional.

PMID- 8994276
TI  - Screening for abnormal illness behaviour.
AB  - A screening test for detecting abnormal illness behaviour in patients with
      somatic symptoms is described here along with its psychometric properties. This
      screening version of the Illness Behaviour Questionnaire (SIBQ) is derived from
      two subscales of the Illness Behaviour Questionnaire and has 11 items. The study
      was carried out on 78 consecutive patients with prominent somatic complaints and
      22 normal volunteers. The SIBQ was administered to the subjects and the
      sensitivity, specificity and hits positive rates were computed for different cut
      off scores. A score of 7 and above gave a sensitivity of 86%, a specificity of
      83% and a hits-positive rate of 0.7537, and this seems the optimal cut-off score.
      The SIBQ may prove to be a sensitive screening instrument to detect probable
      cases of abnormal illness behaviour and especially useful for busy clinics or
      centres.

PMID- 8994277
TI  - Psychological factors in the development of mood disorders with a seasonal
      pattern.
AB  - The psychiatric records of a 7-year period were searched for cases with seasonal
      mood disorders. Among 358 cases with a mood disorder there were 41 patients with
      3 or more admissions, 4 of which were demonstrating a seasonal pattern. It was
      found that the depressive or manic episodes of these patients were anniversary
      reactions associated with intense traumatic experiences in childhood, adolescence
      or adulthood. The seasonal pattern of the depressive episodes fulfilled the DSM
      IV diagnostic criteria. The time and sometimes the place of the traumatic event
      acted as triggers eliciting the clinical symptoms. This study showed that
      anniversary reactions may constitute a subgroup of seasonal mood disorders
      manifesting both depressive and manic episodes, which are precipitated primarily
      by psychological factors rather than climatic conditions.

PMID- 8994278
TI  - Coping styles in abstainers from alcohol.
AB  - The present study investigates the Millon Behavior Health Inventory basic coping
      styles, mental absorption (Tellegen Absorption Scale), sensation seeking (Arnett
      Inventory of Sensation Seeking, AISS) and affect inhibition (Marlowe-Crowne
      Social Desirability Scale, MC-SDS), in a group of abstainers from alcohol (n =
      55) compared to an age-equivalent group of moderate drinkers (n = 176). The
      abstainers had significantly higher scores on one of the repressive coping styles
      (respectful) and significantly lower scores on sociability. There were no
      differences on the other basic coping styles. The abstainer group had lower AISS
      scores and higher MC-SDS scores. There were no significant differences between
      abstainers and drinkers in mental absorption. The results suggest that abstainers
      from alcohol may have adopted an affect-inhibiting, passive-ambivalent coping
      style associated with denial of hostility, rigid impulse control and social
      conformity.

PMID- 8994279
TI  - The multiaxial system of ICD-10: evaluation of a preliminary draft in a
      multicentric field trial.
AB  - The multiaxial system (MAS) of ICD-10, chapter V (F) consists of three axes: axis
      I, clinical syndromes (psychiatric disorders including personality disorders and
      somatic diseases); axis II, disabilities; axis III, environmental/circumstantial
      and personal life-style/life management factors. Results of a multicentric field
      trial evaluating a preliminary draft of the MAS are presented. 45 raters in seven
      German centers made 488 ratings on 12 written case histories. With a mean kappa
      of 0.50 for 3-character diagnoses interrater reliability for axis I was moderate
      although lower than expected from previous field trials. On axis II the WHO
      Disability Diagnostic Scale (WHO-DDS) was compared to the Global Assessment of
      Functioning (GAF) used in DSM-III-R and DSM-IV. For both scales the intraclass
      correlation coefficient showed a moderate interrater reliability (WHO-DDS = 0.62;
      GAF = 0.65). On axis III the number of relevant psychosocial circumstances coded
      by the different raters varied greatly. Interrater reliability was very poor with
      kappa values ranging from 0.03 to 0.55 for the different categories and an
      overall kappa of 0.16.

PMID- 8994280
TI  - Borderline conditions in childhood. A register-based follow-up study over a 22
      year period.
AB  - The ICD-8 diagnosis applicable to borderline psychosis in children is psychosis
      limitaris infantilis (299.02). Results from a register-based study referring to
      all Danish children admitted between 1970 and 1992 and diagnosed borderline
      psychosis are presented here. A total of 415 children (332 boys and 83 girls)
      were admitted with a diagnosis of psychosis limitaris infantilis. At a follow-up
      examination in the Psychiatric Case Register 70% of those diagnosed with
      psychosis limitaris infantilis were found to have been re-admitted at least once
      to a psychiatric hospital. Thirteen percent of the boys and 19% of the girls,
      admitted more than once, had a diagnosis of schizophrenia after 5 years. This
      share increased after a 15-year period of observation to 24% in the group of
      boys, whereas the number of schizophrenic girls remained unchanged. One third of
      the boys and 17% of the girls were diagnosed with personality disorders,
      following a 15-year observation period.

PMID- 8994281
TI  - Vascular endothelial growth factor, a multifunctional polypeptide.
AB  - Angiogenesis, the sprouting of new blood vessels from pre-existing vessels, is a
      complex, multicellular phenomenon involving capillary endothelial cell (EC)
      proliferation, migration, and tissue infiltration. The elucidation of the
      biochemical and molecular factors which control angiogenesis is fundamental to
      our understanding of normal blood vessel development, as well as of the
      pathogenesis of abnormal blood vessel formation. Angiogenesis is associated with
      numerous physiological processes, including embryogenesis, wound healing, organ
      regeneration, and the female reproductive cycle. However, abnormal angiogenesis
      also plays a major role in the pathogenesis of tumor growth, rheumatoid
      arthritis, atherosclerosis and various retinopathies. The cellular and molecular
      mechanisms underlying both physiological and pathophysiological angiogenesis are
      only now beginning to be understood. Vascular endothelial growth factor was
      initially discovered as an unidentified tumor-derived factor which increased
      microvascular permeability (vascular permeability factor, VPF). Subsequently, it
      was determined that the protein exhibited mitogenic effects on endothelial cells,
      but not other cell types. Multiple receptor subtypes have been described which
      may in part explain the multiplicity of biological actions that have been
      ascribed to VEGF/VPF in the literature. In this overview, we briefly summarize
      what is currently known about VEGF and VEGF receptor biology, as well as VEGF
      receptor signal transduction mechanisms in endothelial cells.

PMID- 8994282
TI  - Molecular mechanisms of angiogenesis: experimental models define cellular
      trafficking of FGF-1.
AB  - Numerous studies have established that stimulation of cell growth by members of
      the fibroblast growth factor (FGF) family of polypeptides is dependent upon an
      extracellular pathway. Acidic FGF (FGF-1), however, lacks a classical signal
      sequence for secretion, thereby making it difficult to evaluate regulation of
      biological activity by this growth factor. Efforts in this laboratory have
      utilized molecular techniques of retrovirology and transgenic modeling to
      introduce cDNA sequences encoding either an intracellular or extracellular form
      of FGF-1 into primary diploid cells to examine trafficking and
      compartmentalization of FGF-1. Several lines of evidence obtained from these
      models provide a compelling argument that the stimulation of FGF-1-associated
      cellular transformation is restricted to an extracellular, receptor-mediated
      pathway, involving protein tyrosine phosphorylation and nuclear localization. In
      addition, an unconventional secretion pathway for intracellular FGF-1 has been
      identified that involves mechanisms associated with oxidative stress.

PMID- 8994283
TI  - Smooth muscle cell diversity and the extracellular matrix in a rat model of
      restenosis.
AB  - Clear differences exist in the incidence and severity of atherosclerotic plaques
      that arise in different segments of the arterial tree. Aortic homograft
      transplant experiments in dogs showed that the greater incidence of plaque
      formation in the abdominal versus the thoracic aorta was due to intrinsic
      differences in the cell populations in these two segments rather than to
      hemodynamic factors. What is the basis for SMC diversity within a common vessel
      wall? Recent lineage analysis studies in the avian and mammalian embryo indicate
      that two distinct SMC lineages contribute to the formation of the major elastic
      outflow arteries including the aorta. A mixture of unique SMC types of diverse
      developmental lineages within a common vessel wall raises new questions about the
      potential for SMC type-specific responses to growth factors and cytokines
      involved in human atherosclerosis and restenosis.

PMID- 8994284
TI  - Role of the renin-angiotensin system on cardiac diseases.

PMID- 8994285
TI  - Prevention of recurrent esophageal bleeding and survival in patients with
      alcoholic cirrhosis: a randomized study.
AB  - OBJECTIVES: To compare endoscopic sclerotherapy, propranolol and distal
      splenorenal shunt in the prevention of rebleeding esophageal varices and
      mortality in alcoholic cirrhotics. METHODS: Forty-three alcoholic cirrhotics that
      had bled from esophageal varices were randomized to sclerotherapy (13), shunt
      (15) or propranolol(15). Outcomes measured were rebleeding from varices and
      death. RESULTS: There was no significant difference between the three treatment
      groups in relation to rebleeding rate or death. Continued alcohol consumption did
      not influence outcome. CONCLUSIONS: All three therapies were equally effective in
      preventing rebleeding from varices.

PMID- 8994286
TI  - The 1986 dengue and dengue hemorrhagic fever epidemic in Puerto Rico:
      epidemiologic and clinical observations.
AB  - In 1986 Puerto Rico experienced its eleventh dengue outbreak of this century, but
      the first with simultaneous transmission of three dengue virus serotypes, and the
      first with significant numbers of severe and fatal hemorrhagic disease. Overall,
      10,659 cases were reported; 1,257 cases were laboratory confirmed as having
      current or recent dengue infection. Dengue 4 (DEN-4) was the predominant serotype
      (160/363 isolates, 44%) followed by dengue 1 (DEN-1) with 134 isolates (37%) and
      dengue 2 (DEN-2), 69 isolates (19%). Transmission peaked during September, but
      large numbers of cases occurred through November. Seventy-one (91%) of Puerto
      Rico's 78 municipalities had laboratory-confirmed cases. Fifty-one percent of all
      confirmed cases occurred in metropolitan San Juan. Most cases presented
      clinically as classical dengue fever, but 37% of all confirmed cases were
      reported to have developed some type of hemorrhagic manifestation, and 6%
      reported hematemesis. In addition, 29 laboratory confirmed cases met the WHO case
      definition for dengue hemorrhagic fever, 3 of which were fatal. Among the 29
      laboratory-confirmed cases of dengue hemorrhagic fever/ dengue shook syndrome,
      virus was isolated from 12; one DEN-1, three DEN-2, and eight DEN-4. Among
      laboratory confirmed cases, infants less than one year of age were at greater
      risk of developing dengue hemorrhagic fever/ dengue shook syndrome, hematemesis
      and any reported hemorrhage than were the other age groups evaluated.

PMID- 8994287
TI  - Sequence analysis of the V1-V2 hypervariable region of the HIV-1 envelope gene
      from pediatric patients.
AB  - The presence of HIV-1 DNA sequence variants of pediatric AIDS patients was
      investigated in a two-stage polymerase chain reaction (PCR) using nested primers
      for the first and second (V1-V2) hypervariable regions of the proviral envelope
      (gp 120) gene (env1). Gel electrophoresis analysis yielded amplified DNA bands
      which exhibited length variations which were characteristic for each child. The
      PCR products were cloned and the resulting clones demonstrated inserts of
      different lengths in a patient and between patients. Analysis of five clones from
      two different patients at the level of DNA sequencing indicates an extreme
      heterogeneity in the V1-V2 region. DNA maximum similarity between all of the
      isolated clones ranged between 69 to 96%. Comparison between DNA sequences of the
      isolated clones and HIV-1 strains of other parts of the world was also performed.
      The highest percentage of similarity that was found with known HIV variants
      included the following strains: HIVADA, HIVJFL, HIVSW42, HIVSWB83, HIVTRA2,
      HIVWMJ22. The sequences also showed a high degree of similarity to the clade B
      virus HIVSF162. The analyzed HIV-1 sequences demonstrated the expected high
      degree of variation in the V1-V2 region of the envelope gene and in some cases
      that the variation between isolates from the same patient may exceed the
      variation between the individual clones and the reference HIV-1 strains.

PMID- 8994288
TI  - Crack use in Puerto Rico: evidence of a recent epidemic.
AB  - This study examines the prevalence of crack use among out-of-treatment drug users
      in the San Juan metropolitan area. Of the sample of 849 drug users, 310 (36.5%)
      were crack users only, 179 (21.1%) were drug injectors and crack users, and 360
      (42.4%) were drug injectors only. To study the characteristics of crack users we
      selected the subjects who reported the use of crack only. Of the 310 subjects,
      193 (62.3%) men and 117 (37.7%) women, the mean age was 29 years. Significant
      differences were observed by gender. Females reported higher education, living in
      a nuclear family, crack/cocaine as the first drug used, history of sexually
      transmitted diseases and higher rates of HIV seropositivity. Males were more
      likely to report income from illegal activities, incarceration, use of multiple
      drugs, and more years of drug use. Among those sexually active, females were more
      likely to practice unprotected vaginal sex, have multiple sex partners, engage in
      prostitution (exchange of sex for money and/or drugs) and use condoms.

PMID- 8994290
TI  - Mycobacterium tuberculosis infection among crack and injection drug users in San
      Juan, Puerto Rico.
AB  - This study aims to determine the prevalence of Mycobacterium tuberculosis
      infection and its association with HIV and other health risk factors among drug
      users. A sample of 716 IDUs and crack users were enrolled from community sites.
      Consenting subjects were tested for HIV serum antibody status. Drug users with an
      unknown PPD status were administered a PPD skin test and an anergy panel of three
      antigens (Candida, mumps and tetanus). Overall, 68 (10.3%) were reactive to the
      PPD skin test, 240 (34.7%) were HIV positive and 195 (29.5%) showed cutaneous
      anergy. Participants infected with tuberculosis (TB) were more likely to be HIV
      seropositive, and to have a history of incarceration and residential drug
      treatment than those not infected. In addition, TB infection was more prevalent
      among intravenous drug users (IDUs) and shooting gallery managers. These findings
      suggest that drug users should be considered at high risk for TB and HIV
      infection. Innovative programs to monitor both infections among drug users are
      needed to arrest what can become a dual epidemic of HIV and TB in the near
      future.

PMID- 8994289
TI  - Risk factors for shooting gallery use among drug injectors in Puerto Rico.
AB  - Needle sharing is one of the principal risk behaviors leading to HIV transmission
      among injection drug users (IDUs). Shooting galleries, a social context where
      IDUs rent, share, and borrow needles, are locations usually found near drug
      markets. This study, which interviewed 1,700 IDUs from May 1989 to June 1990,
      assesses sociodemographic characteristics and HIV risk behaviors among shooting
      gallery users in Puerto Rico. Multivariate analyses showed that shooting gallery
      use is associated with speedball (a concoction of heroin and cocaine) injection,
      income from illegal activities and previous drug treatment. Shooting gallery
      users were more likely to rent, share, and borrow needles, and less likely to
      always use bleach and water to clean needles. Strategies to reduce shooting
      gallery use among drug injectors are discussed.

PMID- 8994291
TI  - Pension benefits among the aged: conflicting measures, unequal distributions.
AB  - Estimates of total benefits paid by employer sponsored pension plans seem to vary
      widely between different data sources and measures. Such discrepancies have been
      used to support differing conclusions about the effectiveness of the pension
      system. This article examines several measures of aggregate pension benefits in
      1990, a year particularly rich in available data. Exploratory analysis suggests
      that the greatest source of discrepancy lies in differing treatments of lump-sum
      distributions, although the study also identifies several other types of payments
      that are variously, and erroneously, counted as pension income. Age of recipients
      is an important factor in analyzing different measures of aggregate pension
      benefits; discrepancies are much smaller among the aged than in the population as
      a whole. The analysis also provides new evidence about the unequal distribution
      of pension benefits among the aged, confirming from two data sources that
      benefits are heavily concentrated among higher income groups.

PMID- 8994292
TI  - Poverty among single elderly women under different systems of old-age security: a
      comparative review.
AB  - This study takes stock of available comparative research on the economic status
      of elderly single women in six industrialized countries: France, Germany, the
      Netherlands, Sweden, Switzerland, and the United States. A systematic comparison
      of income has become easier due to such standardized data bases as the Luxembourg
      Income Study. But an explanation for different poverty rates among older women
      who are on their own requires a further, differentiated assessment of the
      countries' retirement benefit structures. This article attempts such a review. It
      makes use of a variety of single-country sources and takes into account the
      institutional heterogeneity of old-age security systems. The study concludes with
      a view of the effectiveness of different old-age security systems in preventing
      poverty among older single women.

PMID- 8994293
TI  - Privatizing Social Security: the Chilean experience.
AB  - In 1981, Chile introduced a new approach to social insurance, a system of
      individual capitalization accounts financed solely by the employee. This new
      privatized system was an improvement over Chile's failing pay-as-you-go
      arrangement. As many countries worldwide are facing financial problems with their
      social security system, they are now looking to the Chilean model in trying to
      find solutions. This article describes the conditions that led to the new system,
      the transition, and details of the new privatized system.

PMID- 8994294
TI  - Aberrant crypt foci in the colonic mucosa of rats treated with a genotoxic and
      nongenotoxic colon carcinogen.
AB  - Aberrant crypt foci (ACFs) are putative preneoplastic lesions in the colonic
      mucosa identified by examining methylene blue-stained whole mounts of colon. ACFs
      have been previously described in rats treated with genotoxic colon carcinogens.
      This study determined whether or not a nongenotoxic colon carcinogen could induce
      ACFs and compared the morphology of these ACFs with those induced by a genotoxic
      colon carcinogen. Six-wk-old Fischer-344 rats were administered dextran sulfate
      (DSS, nongenotoxin) in the drinking water or azoxymethane (AOM, genotoxin) by
      single subcutaneous injection. Rats were sacrificed at 9 and 14 wk after study
      initiation. Colons were fixed and stained with methylene blue, and the mucosal
      surface of transilluminated whole mounts was examined with a microscope. The
      number of ACFs and number of crypts per focus (multiplicity) were recorded.
      Representative ACFs were processed into glycol methacrylate for hexosaminidase
      enzyme histochemistry and sections of the remaining colon containing ACFs were
      embedded in paraffin for morphologic evaluation. In whole mounts, ACFs from AOM-
      and DSS-treated rats had elongated slit-to-oval-shaped lumens surrounded by a
      thickened and intensely stained epithelium. DSS-induced aberrant crypts differed
      from those induced by AOM in that they were frequently larger, tended not to form
      discrete foci circumscribed by normal crypts, and were located adjacent to
      ulcers. Total ACFs and large foci (4 or more crypts/focus) were significantly
      more numerous in AOM-treated rats at both time points. Histologically, DSS
      induced ACFs had segmental to diffuse loss of hexosaminidase activity, mucin
      depletion to increased prominence of goblet cells, and marked distortion of crypt
      architecture. AOM-induced ACFs had diffuse loss of hexosaminidase activity,
      variable depletion of mucin, and less distortion of crypt architecture. Variable
      degrees of epithelial dysplasia were seen in ACFs with both carcinogens, but
      dysplasia was more severe in DSS-induced ACFs. Colonic mucosal neoplasms were
      induced by both carcinogens. In subchronic studies, the ACF assay may be a useful
      method to improve the identification and characterization of xenobiotic-induced
      changes in colonic mucosal crypts.

PMID- 8994295
TI  - Immunohistochemical demonstration of the gap junctional protein connexin 32 and
      proliferating cell nuclear antigen in glutathione S-transferase placental form
      negative lesions of rat liver induced by diethylnitrosamine and clofibrate.
AB  - The distributions of a gap junctional protein, connexin 32 (cx 32), and
      proliferating cell nuclear antigen (PCNA) were examined immunohistochemically in
      glutathione S-transferase placental form (GST-P)-negative foci, induced in rat
      liver by initiation with diethylnitrosamine (DEN, 200 mg/kg) followed by
      promotion with clofibrate (1% in diet) in an in vivo medium-term assay system for
      hepatocarcinogenesis. The results were compared to those in GST-P-positive foci
      induced by DEN alone. The treatment with clofibrate caused the appearance of GST
      P-negative foci, increased in size as compared to GST-P-positive foci in the same
      liver or induced by the DEN alone. The proportion of PCNA-positive hepatocytes in
      GST-P-negative foci was significantly higher than in the surrounding parenchyma,
      indicating increased cell proliferation. The numbers of cx 32-positive spots per
      hepatocyte in GST-P-negative foci were clearly decreased, reaching 65.4% at week
      20 and 51.8% at week 30 of values for surrounding normal hepatocytes. In GST-P
      positive foci induced by DEN, only a slight decrease (80%) was observed at week
      8. These findings show that a positive association between the sustained
      inhibition of gap junctional intercellular communication and increased cell
      proliferation of GST-P-negative foci in Fischer-344 male rats induced with DEN
      and promoted with clofibrate.

PMID- 8994296
TI  - Neoplastic response in Japanese medaka and channel catfish exposed to N-methyl-N'
      nitro-N-nitrosoguanidine.
AB  - Japanese medaka (Oryzias latipes) and channel catfish (Ictalurus punctatus) were
      investigated for carcinogenic response following a 28-day, 3 x/wk pulse exposure
      to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Five-wk-old medaka were exposed
      at concentrations of 0, 0.5, and 1.0 mg/L, and 5-mo-old catfish at concentrations
      of 0, 0.1, and 0.5 mg/L. In medaka, a total of 19 tumors including 2
      branchioblastomas, 6 thyroid follicular adenomas and 1 adenocarcinoma, and 11
      subcutaneous fibrosarcomas were observed in 16 of 96 MNNG-exposed fish. In
      catfish, a total of 37 tumors including 4 squamous cell carcinomas and 16
      papillomas, 3 lipomas, 1 fibroma, 1 osteosarcoma, 4 branchioblastomas, 6 thymic
      epithelial tumors, and 2 generalized lymphosarcomas were observed in 34 of 172
      MNNG-exposed fish. The induction of neoplasms in medaka was primarily in the
      gill, thyroid, and subcutis of the cervical and trunk regions, whereas in catfish
      skin, thymus, oro-pharynx, and hemopoietic tissues were also commonly affected.
      In both species, the neoplastic response was considered to be related to direct
      exposure of the tissues to MNNG. Some of these tumors have not been reported in
      the literature in either natural or experimental fish. The results also suggest
      species-specific differences in carcinogenic response following MNNG exposure.

PMID- 8994297
TI  - Clinical pathologic changes in two marmosets with wasting syndrome.
AB  - Two sexually mature marmosets (Callithrix jacchus) showing clinical signs similar
      to those seen in wasting marmoset syndrome (weight loss, decreased muscle mass,
      and alopecia) were evaluated for clinical and anatomic pathologic changes. The
      most prominent clinical pathologic alterations included macrocytic normochromic
      anemia, hypoproteinemia, hypoalbuminemia, elevated serum aspartate
      aminotransferase and alkaline phosphatase levels, and previously unreported
      changes of thrombocytosis. The principal gross and histopathologic finding was
      chronic colitis, which appeared to be the most important contributing factor to
      the development of wasting syndrome in these marmosets.

PMID- 8994298
TI  - Spontaneous lesions in aging FVB/N mice.
AB  - The FVB/N mouse strain was created in the early 1970s and has since been used
      extensively in transgenic research because of its well-defined inbred background,
      superior reproductive performance, and prominent pronuclei of fertilized zygotes,
      which facilitate microinjection of DNA. Little is known, however, about the
      survivability and spontaneous disease of nontransgenic FVB/N mice. Therefore, the
      purpose of this study was to determine survival to 24 mo of age and the incidence
      of neoplastic and nonneoplastic disease at 14 and 24 mo of age. At 14 mo of age,
      the incidence of tumor-bearing mice was 13% in males (n = 45) and 26% in females
      (n = 98). All tumors in males and most in females at this time were alveolar
      bronchiolar (AB) neoplasms of the lung. Survival to 24 mo of age was
      approximately 60% in both sexes (29/50 males, 71/116 females), and the incidence
      of mice with tumors at this time was 55% in males and 66% in females. In
      decreasing order of frequency, the following neoplasms were observed in > 5% of
      subjects: in males, lung AB tumors, liver hepatocellular tumors, subcutis neural
      crest tumors, and Harderian gland adenomas; in females, lung AB tumors, pituitary
      gland adenomas, ovarian tumors (combined types), lymphomas, histiocytic sarcomas,
      Harderian gland adenomas, and pheochromocytomas. Compared with other mouse
      strains, the observed incidences of tumors in FVB/N mice suggest a higher than
      usual rate of lung tumors and a lower than usual incidence of liver tumors and
      lymphomas. This tumor profile should be considered in the interpretation of
      neoplastic phenotypes in FVB/N-derived transgenic lines.

PMID- 8994300
TI  - A critical appraisal of the value of the mouse cancer bioassay in safety
      assessment.
AB  - Substantial progress in understanding nongenotoxic or secondary mechanisms of
      tumorigenesis has been made over the past decade. However, the methods used in
      regulated studies for assessment of carcinogenic potential in chemicals in
      development have not evolved significantly. Based on the experience of over 30 yr
      of testing and the societal need to control costs, reevaluation of standard
      cancer rodent bioassay protocols is being done. Expert consensus after evaluating
      the results of full-scale rodent bioassays of both sexes in 2 species is that a
      reduced protocol is acceptable. After review of relevant data, it is our opinion
      that cancer hazard assessment in male and female rats only would be sufficient
      and that, in the future, mouse bioassays will not add significant value on a
      routine basis. We are unable to find an example of a mouse tumorigenic finding
      that predicts a confirmed or probable human response with negative findings in a
      rat bioassay. The savings realized by eliminating mouse testing from routine
      protocols would be substantial and better spent in expanding short-term studies
      to add to our understanding of chemical carcinogenesis.

PMID- 8994301
TI  - The contribution of the mouse in hazard identification studies.
AB  - Because three is usually more extensive toxicity, metabolism, and pharmacokinetic
      information for pharmaceuticals as opposed to environmental agents, including
      pesticides, the argument has been made that carcinogenicity testing in two rodent
      species may not have been necessary for carcinogenicity testing of
      pharmaceuticals. On the basis of numerical data only, it may be argued that
      carcinogenicity testing of pharmaceuticals in one species, typically the rat, is
      sufficient to identify potential human carcinogens. The argument that testing in
      a second species, typically the mouse, is redundant overlooks the value added by
      the second species carcinogenicity study. Bioassay data from the second species
      allows balance and perspective in evaluating the observed effects, and this is
      especially critical when there is a marginal, questionable, or inconclusive
      response in one species. Utilization of two species for carcinogen identification
      is the principal means for identifying trans-species carcinogens-those mostly
      likely to be carcinogenic in humans. Given that neither rat nor mouse are ideal
      surrogates for humans, concordant data from both species strengthens the ability
      to extrapolate findings to humans. We believe that testing in two species should
      continue to be the default approach used for carcinogen hazard identification
      whenever scientifically indicated until such time that acceptable and suitable
      alternatives are available. To utilize only one species for this important means
      of protecting human health is premature at this time.

PMID- 8994302
TI  - Rat or mouse cancer bioassay--or none of the above?

PMID- 8994299
TI  - Disruption of cyclooxygenase genes in mice.

PMID- 8994303
TI  - Effect of food restriction on risk assessment.

PMID- 8994304
TI  - Possible mechanisms underlying the antiaging actions of caloric restriction.
AB  - Restricting the food intake of mice and rats to well below that of ad libitum-fed
      animals markedly slows the aging processes. This action is reflected in an
      increase in longevity, a decrease in the age-associated increase in age-specific
      mortality rate, the maintenance of the physiological processes in a youthful
      state even at advanced ages, and the delaying of the onset or slowing of the
      progression or both of most age-associated diseases. The dietary factor
      responsible is the reduction in energy (caloric) intake. Many hypotheses have
      been proposed regarding mechanisms underlying this antiaging action. Hypotheses
      relating the antiaging action to the retardation of growth and development, the
      reduction of adipose mass, and the reduction of metabolic rate have been found to
      be wanting. Two of the proposed hypotheses have some evidence in their support.
      One involves the altered metabolic characteristics of glucose fuel use and of
      oxidative metabolism. The other relates to the enhanced ability of the rodents
      restricted in food intake to cope with challenges, which in turn has been linked
      to the glucocorticoid system and to the heat-shock protein system.

PMID- 8994305
TI  - The retardation of aging by caloric restriction: studies in rodents and primates.
AB  - Caloric restriction (CR), which has been investigated by gerontologists for more
      than 60 yr, provides the only intervention tested to date in mammals (typically
      mice and rats) that repeatedly and strongly increases maximum life span while
      retarding the appearance of age-associated pathologic and biologic changes.
      Although the large majority of rodent studies have initiated CR early in life (1
      3 mo of age), CR started in midadulthood (at 12 mo) also extends maximum life
      span in mice. Two main questions now face gerontologists investigating CR. By
      what mechanisms does CR retard aging and disease processes in rodents? There is
      evidence to suggest that age-associated increases in oxidative damage may
      represent a primary aging process that is attenuated by CR. Will CR exert similar
      actions in primates? Studies in rhesus monkeys subjected to CR and limited human
      epidemiological data support the notion of human translatability. However, no
      matter what the answers are to these questions, the prolongation of the health
      span and life span of rodents by CR has major implications for many disciplines,
      including toxicologic pathology, and raises important questions about the
      desirability of ad libitum feeding.

PMID- 8994306
TI  - Diet: the neglected variable in chemical safety evaluations.
AB  - The objectives of this review are to alert the community of toxicologic
      pathologists to the types and significance of various diets fed to experimental
      animals used in safety evaluations of drugs and other chemicals, to acquaint
      investigators with dietary nutrients and contaminants of significance to research
      animals, to review some of the consequences of improper or inadequate diets on
      results of safety evaluations, and, finally, to offer a brief introduction to a
      highly promising new digital specimen technology for evaluating histopathology of
      tissues from animals used in safety evaluations with the aid of computers.
      Results that form the basis for this review have accumulated for more than 4
      decades during research conducted during appointments at the University of
      Missouri, Columbia; Auburn University; Massachusetts Institute of Technology; and
      Boston University School of Medicine. The methods used in these studies have
      generally been state-of-the-art at the time the studies were conducted and
      involved an integration of techniques and methods used in fundamental nutrition,
      toxicology, and experimental pathology. Some of these investigations have shown
      that contaminants, naturally occurring and man-made, intentional and
      nonintentional, do occur in commercial animal diets; that essential nutrients,
      including total calories, protein and fat, can be provided in less or more than
      adequate amounts for the species of animal used in safety evaluations; and that
      such variables can influence responses to chemicals through effects on xenobiotic
      metabolism, immunocompetence, secondary diseases, and other factors. Under such
      conditions, serious differences in final interpretation of human risk for a drug
      or other chemical can contribute to failure to gain approval for a potentially
      valuable therapeutic agent. This review discusses the significance of various
      dietary components with examples of their effects on response of the animal to
      chemicals and demonstrates why nutrients, new technologies for assessing their
      effects, and other components in the diet should be accorded greater
      consideration by investigators and regulators.

PMID- 8994308
TI  - Rationale for the use of dietary control in toxicity studies--B6C3F1 mouse.
AB  - Significant variability in critical study parameters such as tumor incidences and
      survival, increasing tumor incidence and decreasing survival in common toxicity
      test models, and agent-induced changes in body weight (BW) and BW distribution
      all generate concern about the reproducibility, consistency, and equity of
      chronic toxicity tests used in regulation. These concerns have led to suggestions
      to control BW in chronic tests by the modulation of dietary intake without
      inducing malnutrition [dietary control (DC)] thereby minimizing tumor and
      survival variability both between and within studies. Evaluating the reports of
      the best controlled set of chronic experiments, the National Toxicology Program
      bioassay series, from studies initiated from 1981 to 1990, there is an increase
      in tumor incidence, especially liver tumors, with a consistent increase in BW.
      The studies are classified as to whether normal or aberrant BW growth curves
      occur. When the studies with normal growth curves are considered, the variance in
      the BW at 12 mo on test (BW12) can account for over 50% of the variance in liver
      tumor incidence. Additional stratification by study type, which alter tumor
      prevalences, as well as appreciation of housing effects [group housing decreases
      survival (in male mice) and induces tumors in males and females when compared to
      individual housing], further increase the strength of the correlations,
      accounting for up to 90% of the variance seen in tumor incidences. These updated
      analyses further support the hypothesis that it is the BW variation that is
      resulting in much of the variability seen in tumor incidences and refine the
      suggestions for the BW curves used as the desired targets for DC.

PMID- 8994307
TI  - The effects of diet, ad libitum overfeeding, and moderate dietary restriction on
      the rodent bioassay: the uncontrolled variable in safety assessment.
AB  - Ad libitum (AL) overfeeding is the most significant, uncontrolled variable
      affecting the outcome of the current rodent bioassay. There is a highly
      significant correlation between AL food consumption, the resultant obesity and
      body weight, and low 2-yr survival in rodents. AL feeding of diets with lowered
      protein, metabolizable energy (ME), and increased fiber does not improve
      survival. Only dietary restriction (DR) of all diets tested significantly
      improves survival and delays the onset of spontaneous degenerative disease (i.e.,
      nephropathy and cardiomyopathy) and diet-related tumors. Moderate DR results in
      an incidence of spontaneous tumors similar to AL-fed rats, but the tumors are
      found incidentally and do not cause early mortality. There is a decreased age
      adjusted incidence of pituitary and mammary gland tumors in moderate DR-fed rats,
      but tumor growth time is similar between AL and DR rats with only a delay in
      tumor onset time seen in DR-fed groups. Moderate DR does not significantly alter
      drug-metabolizing enzyme activities nor the toxicologic response to 5
      pharmaceuticals tested at maximum tolerated doses (MTDs). However, moderate DR
      fed rats did require much higher doses of 4 additional pharmaceutical compounds
      before classical MTDs were produced. Toxicokinetic studies of 2 of these
      compounds demonstrated equal or higher steady-state systemic exposures to parent
      drug and metabolites in moderate DR-fed rats. Markers of oxidative stress (lipid
      peroxidation, protein oxidation) are decreased and cytoprotective anti-oxidant
      markers are preserved in moderate DR-fed rats. But moderate DR does not delay
      reproductive senescence in female rats. Only marked DR delays reproductive
      senescence compared to AL and moderate DR-fed female rats. These and other data
      indicate that moderate DR is the most appropriate method of dietary control for
      the rodent bioassay when used to assess pharmaceuticals for human safety and
      compounds for risk assessment.

PMID- 8994309
TI  - FDA points-to-consider documents: the need for dietary control for the reduction
      of experimental variability within animal assays and the use of dietary
      restriction to achieve dietary control.
AB  - Standard protocols for conducting chronic toxicity and carcinogenicity studies
      have been refined over the years to carefully control for many variables.
      Nevertheless, over the last 2 decades, there has been a steady increase in
      variability, a decrease in survival, an increase in tumor incidence rates, and an
      increase in the average body weight of control animals among the various rodent
      species and strains used for toxicity testing. These observations have prompted
      an evaluation of chronic study designs to determine what factor(s) may be
      responsible for such confounding changes. Ad libitum feeding and the selection of
      successful breeders with rapid offspring growth is believed to be at least
      partially responsible for the heavier, obese rodents with which many laboratories
      are coping today. As a result of these changes, some studies used for the
      evaluation of safety have been deemed inconclusive or inadequate for regulatory
      purposes and either additional supportive studies have been requested and/or
      studies per se have been repeated. Research on the molecular mechanisms of
      caloric restriction and agent-induced toxicity at the Food and Drug
      Administration (FDA) National Center for Toxicological Research stimulated the
      first international conference on the biological effects of dietary restriction
      in 1989; this was followed in 1993 by an FDA workshop exploring the utility of
      dietary restriction in controlling reduced survival in chronic tests and an
      international conference in 1994 exploring the implications for the regulatory
      community of using dietary restriction in toxicity and carcinogenicity studies
      used in support of a sponsor's submission or in risk assessments. The outcome of
      that conference was the FDA's commitment to develop Points-to-Consider documents
      that address the issue of dietary control in chronic toxicity and carcinogenicity
      studies.

PMID- 8994310
TI  - Aberrant crypt foci: new insights into the early events of colon carcinogenesis
      induced by genotoxic and nongenotoxic carcinogens.

PMID- 8994311
TI  - "Have you seen this?" Bone anti-resorptive properties of bisphosphonates.

PMID- 8994312
TI  - A symposium summary and perspective on comparative molecular biology of cancer.

PMID- 8994313
TI  - Study of booster doses of two Haemophilus influenzae type b conjugate vaccines
      including their interchangeability.
AB  - A prospective, two center study of 319 children was undertaken to assess
      responses to booster immunization in healthy 18-month-olds who completed primary
      immunization 12 months earlier with Haemophilus influenzae type b (Hib) conjugate
      vaccine (either HbOC or PRP-T). Interchangeability of these products as boosters
      was also assessed, using combination products containing diphtheria, pertussis
      and tetanus components. The study was randomized and evaluator blinded. Sera
      obtained prior to booster vaccination and 4 weeks later were tested for anti-PRP
      using an IgG-specific enzyme immunoassay. Pre-immunization anti-PRP levels were
      low: unmeasurable levels (< 0.06 microgram ml-1) were present in 47% of those
      primed with HbOC and 35% of those primed with PRP-T (P < 0.05). Most children
      responded strongly to booster vaccination. Interchanging the products had no
      detrimental effect. Children who lacked measurable antibody prior to re
      vaccination had significantly weaker responses 4 weeks afterward. Earlier Hib
      booster vaccination should be considered in Canada to avoid low anti-PRP trough
      levels. Extended follow-up of antibody levels and vaccine protective efficacy is
      also advisable given the observed heterogeneity of responses to booster
      vaccination.

PMID- 8994314
TI  - Immunogenicity and reactogenicity of a combined hepatitis A and B vaccine in
      young adults.
AB  - The aim of this study was to assess the immunogenicity and reactogenicity of a
      combined vaccine against hepatitis A virus (HAV) and hepatitis B virus (HBV) in
      young healthy adults. A total of 150 subjects (20 +/- 1.4 years; 111 females and
      39 males) negative for anti-HAV, anti-HBs, anti-HBc and HBsAg markers, were
      enrolled and randomized to received the study vaccine from one of the three lots
      under double blind conditions. Three doses of the combined vaccine were
      administered by intramuscular route (deltoid) following a 0-, 1- and 6 months
      schedule. Each dose of 1 ml contained at least 720 ELISA Units of HAV antigen
      (Strain HM175) and 20 micrograms of recombinant HBsAg. Blood samples for anti-HAV
      (ELISA), anti-HBs (RIA) and transaminases determinations were obtained 1 month
      after the administration of each dose and before to the administration of the
      third dose (month 6). Local and general reactions were recorded by the vaccinee
      on the day of each vaccination and for the three following days on symptom
      sheets. A total of 147 subjects completed the study. There were not statistically
      significant differences between groups regarding to immunogenicity. All subjects
      had seroconverted [geometric mean titres (GMT): 1311 mIU ml-1] for hepatitis A
      component following the second dose; GMT increased to 8895 mIU ml-1 after the
      third dose. Seroconversion rates for hepatitis B component were 98% (GMT, 104 mIU
      ml-1) after the second dose and 100% after the third dose (GMT, 7097 mIU ml-1).
      There were not statistically significant differences between groups regarding to
      incidence of local and general symptoms. Soreness at the injection site and
      headache were the most commonly local and general symptoms reported, following
      42% and 11% of the doses, respectively. This vaccine when given to young adults
      was well tolerated and induced high immunogenic response, similar to that
      obtained by hepatitis A and hepatitis B vaccines administered separately in
      previously reported trials.

PMID- 8994315
TI  - In vivo distribution of radioactivity in mice after injection of biodegradable
      polymer microspheres containing 14C-labeled tetanus toxoid.
AB  - Radiolabeled tetanus toxoid (TT) was prepared by detoxifying chromatographically
      purified tetanus toxin with 14C-labeled formaldehyde. 14C-TT was encapsulated
      inside poly (D,L-lactide-co-glycolide, 50/50) microspheres (MS) of varying
      average size (approximately 10 microns and approximately 50 microns). Balb/c mice
      were injected subcutaneously with 5 Lf (approximately 15 micrograms) of 14C-TT,
      encapsulated in MS, mixed with blank MS without encapsulated antigen, as soluble
      antigen or adsorbed onto aluminum phosphate (AlPO4) and radioactivity was
      monitored at the site of injection, draining lymph nodes, blood, liver, spleen,
      and kidneys at various intervals. At one day, approximately 95% and 90%
      radioactivity disappeared from site of injection for soluble TT or blank MS mixed
      TT and AlPO4 adsorbed TT, respectively, whereas approximately 55% and 70%
      radioactivity disappeared from site of injection for MS of average size
      approximately 50 microns and approximately 10 microns, respectively. By 7 days,
      99% of radioactivity disappeared from site of injection for soluble TT or blank
      MS mixed TT, whereas 2-3% radioactivity persisted at the site of injection for
      AlPO4 adsorbed TT for 4 weeks. In contrast, approximately 20% radioactivity
      stayed at the site of injection for MS injected mice up to 4 weeks. At all time
      points, large MS (approximately 50 microns) showed more radioactivity at the site
      of injection than small MS (approximately 10 microns). Other organs showing
      radioactivity were draining lymph nodes and kidneys. Small MS with encapsulated
      TT showed highest level of radioactivity in lymph nodes at 4 h. In kidneys,
      soluble and AlPO4 adsorbed TT showed a peak of radioactivity at 4 h whereas TT
      encapsulated in MS showed a peak of radioactivity at 7 days. These results
      indicate that AlPO4 did not act as a depot for TT at the site of injection, but
      TT encapsulated in MS did form a depot for approximately 1 month.

PMID- 8994316
TI  - Stabilization of respiratory syncytial virus (RSV) against thermal inactivation
      and freeze-thaw cycles for development and control of RSV vaccines and immune
      globulin.
AB  - A high-titered and stable respiratory syncytial virus (RSV) is essential for the
      development of RSV vaccines and quality control of vaccines and RSV immune
      globulin. We increased the virus titer of RSV seed stock, and virus preparations
      made from this seed stock, 100 times by removing defective interfering particles
      using limiting dilution procedure. RSV preparations made from the new seed stock
      had infectivity titers ranging from 10(7.6) to 10(8.2) TCID50 per ml for five
      lots made over a period of 3 years. Unstabilized RSV lost most of its infectivity
      at -86 degrees C within 2-3 weeks, at 37 degrees C within 24 hr, at 56 degrees C
      within 3 min and after five freeze-thaw cycles. The high titered virus was
      stabilized at -86 degrees C for 3 years, at 37 degrees C for 3 days, at 56
      degrees C for 6 min and against five freeze-thaw cycles. Most effective
      stabilizers included 25% sucrose, 10% trehalose and 45% fetal bovine serum (FBS)
      in Medium 199 whereas 3.5% dimethyl sulfoxide, > or = 45% FBS in phosphate
      buffered saline, 40% glycerol and 10% sorbitol also stabilized RSV to lesser and
      variable degrees. A mixture of 0.5% gelatine and 0.3% sodium glutamate stabilized
      the virus for a short period whereas 0.1 M MgCl2 and 25% FBS did not stabilize
      the virus. The stabilized high-titered virus is very useful for achieving
      reproducibility in serologic assays. A broad spectrum of stabilizers, such as
      those evaluated in this study, would be useful in choosing the most suitable
      formulation for stabilizing a live RSV vaccine.

PMID- 8994317
TI  - Tick-borne encephalitis: development of a paediatric vaccine. A controlled,
      randomized, double-blind and multicentre study.
AB  - A total of 522 children between 18 months and 14 years and 191 adults between 18
      and 60 years were vaccinated with TBE-vaccine according to an abbreviated
      schedule (0, 7, 21). The aim of the study was to investigate whether reducing the
      amount of antigen in the vaccination for children would preserve an adequate
      immune response and decrease the rate of side-effects. Efficacy was determined on
      the extent to which children, vaccinated with the low doses (0.4 microgram or
      0.75 microgram), reacted by developing antibodies in the same way as adults
      treated with the approved dose of 1.5 micrograms (equivalence of titres). The
      titres obtained in the children with the two lower doses were equivalent to those
      in the adults obtained with the standard dose. Titres decreased in the children
      with increasing age. Children older than 12 years in the approved dosage group
      had the same median titres as adults. The frequency of side-effects in the two
      lower dose groups, especially raised temperature, was markedly reduced. Whereas
      30.1% of the children vaccinated with the approved dose had raised temperature
      higher than 38 degrees C only 18.8% and 18.4%, respectively, of the children
      vaccinated with the lower doses developed such temperatures. This improved
      tolerance in terms of raised temperature was also reflected in the other general
      reactions such as tiredness, joint pain or headache.

PMID- 8994318
TI  - Single dose, polymeric, microparticle-based vaccines: the influence of
      formulation conditions on the magnitude and duration of the immune response to a
      protein antigen.
AB  - Ovalbumin-loaded poly (D,L-lactide co-glycolide) [OVA-loaded PLG] microparticles,
      produced by emulsion/solvent evaporation stimulated the production of high serum
      IgG antibody levels after a single subcutaneous (s.c.) administration in mice and
      the duration of the immune response paralleled the degradation rate of the
      carrier. Formulations based on slow resorbing PLG maintained relatively constant
      peak antibody levels for 26 weeks and high titres for over 1 year at a level
      approximating the peak response to the faster resorbing, OVA-loaded particles
      which was of lower duration. Vaccine formulations prepared by simple mixing of
      blank PLG microparticles and OVA exhibited low primary immune responses which
      were only elevated by boosting. OVA-loaded PLG microparticles exhibited a
      substantial surface protein component amounting to ca 40% and 60% of the total
      protein loading for slow resorbing and fast resorbing PLG, respectively. These
      findings suggest that sustained presentation of surface protein to the immune
      system was a major factor in the induction and long-term maintenance of high
      antibody titres following a single s.c. administration of OVA-loaded
      microparticles.

PMID- 8994319
TI  - Two year old hepatitis A vaccine is as good as new.
AB  - This was a randomized, controlled, double-blind study assessing the
      reactogenicity and immunogenicity of newly produced vs 2 year old hepatitis A
      vaccine. Overall 215 non-immune volunteers, 18-39 years old were divided into
      four groups and administered vaccine at months 0, 1 and 6. Three groups each
      received a different vaccine lot which had been stored at 4 degrees C for 2
      years, and one group received recently produced vaccine as control. The mean
      local and general adverse reaction rates were 59.1% and 17.4%, respectively, and
      all vaccinees had seroconverted by month 2. There were no significant differences
      in geometric mean anti-hepatitis A virus (HAV) antibody titres between the four
      groups. In conclusion 2 year old HAV vaccine is safe and equally immunogenic as
      newly produced vaccine.

PMID- 8994321
TI  - Development of a replication-deficient recombinant vaccinia virus vaccine
      effective against parainfluenza virus 3 infection in an animal model.
AB  - The highly attenuated, replication-deficient, modified vaccinia virus Ankara
      (MVA) was used to express the fusion (F) and/or hemagglutinin-neuraminidase (HN)
      glycoproteins of parainfluenza virus 3 (PIV3). Initial recombinant viruses in
      which the HN gene was regulated by a very strong synthetic earlyllate promoter
      replicated poorly in permissive chick embryo cells evidently due to toxic levels
      of the gene product. This result led us to construct and evaluate a modified
      earlyllate promoter derived from the H5 gene of vaccinia virus. Reporter gene
      experiments indicated that the enhanced H5 promoter was about five times stronger
      than the 7.5 promoter used in previous recombinant vaccinia/ PIV3 viruses.
      Although the overall expression from the modified H5 promoter was less than that
      of the strong synthetic promoter, early expression, determined in the presence of
      an inhibitor of DNA replication, was higher. Importantly, recombinant MVA
      employing the modified H5 promoter to regulate the F or HN gene of PIV3
      replicated to high titers in chick cells and expressed functional F or HN
      proteins as measured by syncytial formation upon dual infection of mammalian
      cells. Cotton rats inoculated with recombinant MVA expressing F or HN by
      intramuscular or intranasal routes produced high levels of antibody. The virus
      expressing HN, however, was the more effective of the two in inducing immunity to
      PIV3 challenge, reducing PIV3 viral titers in the nasal turbinates by at least
      4.7 logs and in the lungs by 3.4 logs, similar to that achieved by immunization
      with PIV3. These studies support further testing of recombinant MVA/PIV3 viruses
      as safe and effective candidate vaccines.

PMID- 8994320
TI  - Induction of sustained and elevated immune responses to weakly immunogenic
      synthetic malarial peptides by encapsulation in biodegradable polymer
      microspheres.
AB  - Biodegradable microspheres (MS) based on poly(D,L-lactide) and poly(D,L-lactide
      coglycolide) have the capacity to release encapsulated antigens over defined
      lengths of time depending on their composition and to elicit and sustain strong
      and long-lasting immune responses to protein antigens. In the present study, two
      synthetic multiple antigenic peptides (MAP), P30B2 and (NANP)6P2P30, were
      incorporated into MS of different compositions. P30B2 and (NANP)6P2P30 are
      composed of one or two universal T helper epitopes from tetanus toxin, 947-967
      (P30) and 830-843 (P2), and of a B cell epitope derived from the repeat sequence
      of Plasmodium berghei or Plasmodium falciparum, respectively. BALB/c mice were
      immunized with these two peptides in different formulations, including individual
      MS or mixtures of MS with various release properties, Incomplete Freund's
      adjuvant (IFA) or as soluble peptides. MS formulations elicited strong and
      sustained proliferative and antibody responses comparable to those obtained with
      the IFA preparations. Furthermore, MS formulations induced specific isotype/
      subclass antibodies similar to those induced by IFA. No significant augmentation
      of total serum IgE was detected during this study. In addition, a boosting effect
      was obtained when the immunized mice were reinjected with a small antigen dose in
      IFA several months later. These results indicate that biodegradable MS may be a
      suitable vaccine delivery system/adjuvant not only for protein antigens but also
      for weakly immunogenic synthetic peptides.

PMID- 8994322
TI  - Intestinal and systemic immune responses in humans after oral immunization with a
      bivalent B subunit-O1/O139 whole cell cholera vaccine.
AB  - There is a need for an effective vaccine that can protect against cholera caused
      by either Vibrio cholerae O1 or by the new pandemic serotype O139 Bengal. An oral
      bivalent B subunit-O1/O139 whole cell (B-O1/O139 WC) cholera vaccine has been
      prepared by adding formalin-killed O139 vibrios to the recently licensed oral
      recombinant B-O1 WC vaccine. When tested in Swedish volunteers, this B-O1/O139 WC
      vaccine was found to be safe and immunogenic. Two vaccine doses given 2 weeks
      apart induced statistically significant, P < 0.05, mucosal IgA antibody responses
      in intestinal lavage fluid against cholera toxin in all of nine vaccinees and
      against both O1 and O139 vibrios in seven of nine cases. The intestinal responses
      were associated with similar high frequencies of intestine-derived antibody
      secreting cell responses in peripheral blood to the different antigens. A third
      dose of vaccine given after 5-6 weeks did not result in any further increased
      response. All of 12 vaccinees responded with significant IgA and IgG antitoxin
      responses in serum associated with significant vibriocidal antibody titre rises
      against O1 vibrios in 10 cases (83%) and against O139 vibrios in eight vaccinees
      (67%). The frequencies and magnitudes of the serological responses to the B
      subunit and O1 WC components were similar to those induced by the B-O1 WC
      vaccine. Thus, the O139 component of the vaccine induced intestinal and systemic
      antibacterial immune responses in the majority of the vaccinees, and its addition
      to the vaccine did not interfere with the immunogenicity of the B subunit or O1
      WC components.

PMID- 8994323
TI  - Evaluation of SPf66 malaria vaccine during a 22-month follow-up field trial in
      the Pacific coast of Colombia.
AB  - A double-blind randomized placebo-controlled field trial with the SPf66 malaria
      vaccine was carried out in an endemic area consisting of 14 small villages with
      exclusive fluvial access, in a rain forest area along the Rosario River,
      Colombia. A total of 1257 subjects completed the full three dose vaccination
      schedule on days 0, 30 and 180 (643 vaccinated group/623 placebo group) and were
      followed-up by passive and active surveillance over a period of 22 months. One
      hundred and thirty-four Plasmodium falciparum malaria episodes were detected (53
      in vaccinated group/81 in placebo group), yielding an attack rate of 5.47
      cases/100 person years of follow-up (pyears) in the vaccine group and 8.44/100
      pyears in the placebo group. The estimated vaccine protective efficacy was 35.2%
      (95% CI 8.4-54.2%, P = 0.01). This result supports earlier findings that the
      SPf66 malaria vaccine diminishes the risk of infection by P. falciparum in
      endemic areas of South America.

PMID- 8994324
TI  - Modulation of antigen-specific T and B cell responses influence bacterial
      clearance of non-typeable Haemophilus influenzae from the lung in a rat model.
AB  - This study investigates antigen-specific B and T cell responses following mucosal
      immunization with the major outer membrane protein, P2, from non-typeable
      Haemophilus influenzae (NTHi) and the role of these responses in bacterial
      clearance following pulmonary challenge. Modification of the immunization
      preparation by the inclusion of sodium dodecyl sulphate (SDS) with the adjuvant,
      incomplete Freund's, differentially affects the T and B cell responses to the P2
      antigen. Rats received an intra-Peyer's patch-immunization with P2 with or
      without the inclusion of 1% (w/v) SDS, were boosted via an intratracheal
      administration of P2 alone on day 14, and challenged with live NTHi in the lungs
      on day 21. There were significant differences in the rate of bacterial clearance
      between the different P2-immunized groups and the non-immune group. The inclusion
      of SDS with P2 resulted in enhanced bacterial clearance. This clearance
      corresponded to an enhancement of P2-specific lymphocyte proliferation by CD4+ T
      helper cells but a decrease (reduced approximately 75%) in anti-P2 IgG and IgA in
      both serum and bronchoalveolar lavage washings. P2-specific IgM levels were not
      altered. IgG subclass analysis indicated that the inclusion of SDS had caused a
      significant reduction in IgG2a and an increase in IgG1. The data indicates that
      the magnitude of antibody levels to P2 may not be as important as T cell
      responses in enhancing clearance of NTHi in the lung, in vivo, and that
      immunization targeting enhancement of antigen-specific T cells may be important
      to inducing effective immunity to NTHi.

PMID- 8994326
TI  - Effects of hyperlipidemia on aortic endothelial cell turnover and
      transendothelial macromolecular transport in cholesterol-fed rats.
AB  - BACKGROUND: Hyperlipidemia, hypertension, cigarette smoking and diabetes are some
      major risk factors for atherosclerosis and cardiovascular disease. Repeated
      endothelial injury and enhanced focal intimal influx of plasma lipoproteins are
      the pivotal mechanisms involved in atherogenesis. We previously demonstrated that
      the endothelial cell turnover and associated endothelial permeability were
      significantly increased in the aorta of spontaneously hypertensive rats, chronic
      oral nicotine-treated rats, and streptozotocin-diabetic rats. In the present
      investigation, we examined the effects of hyperlipidemia on arterial endothelial
      cell turnover and transendothelial macromolecular transport in cholesterol-fed
      rats. METHODS: Sixteen male Sprague-Dawley rats were fed a diet containing 5%
      cholesterol for 6 weeks. A group of 14 agematched rats fed a regular diet and
      maintained over the same time period, were served as the controls. In en face
      preparations of the thoracic aorta, mitotic endothelial cells were identified by
      hematoxylin staining, IgG-containing dead endothelial cells were identified by an
      indirect immunoperoxidase method, and endothelial leakage to Evans blue-albumin
      complexes was quantified by fluorescence microscopy. RESULTS: The results showed
      that plasma cholesterol and triglyceride levels were higher in cholesterol-fed
      rats. The hyperlipidemic rats, compared to control rats, had higher values for
      the frequency of endothelial cell death (1.08 +/- 0.28% vs 0.75 +/- 0.16%), the
      frequency of endothelial cell mitosis (0.015 +/- 0.005% vs 0.013 +/- 0.003%) and
      the number density of Evans blue-albumin leaky foci (6.19 +/- 0.64/mm2 vs 5.23 +/
      0.76/mm2) in the aorta. CONCLUSIONS: Similar to the situations in hypertension,
      nicotine consumption and diabetes, the observed trend of increases in the
      frequency of endothelial cell turnover and endothelial permeability to large
      molecules in the aorta of cholesterol-fed rats suggested that these changes may
      contribute to accelerated atherogenesis in hyperlipidemia. However, since rat is
      not a favored animal model for studies of dietinduced hyperlipidemia and
      atherosclerosis, further investigations using other animal models such as rabbit,
      are needed to verify these observations.

PMID- 8994325
TI  - Mycoplasma pneumoniae reinfection and vaccination: protective oral vaccination
      and harmful immunoreactivity after re-infection and parenteral immunization.
AB  - Animal model studies of Mycoplasma pneumoniae infection after live respiratory
      challenge were conducted to investigate the issues of challenge-rechallenge
      associated accentuated pathology, postparenteral vaccination associated
      accentuated pathology, and oral vaccination. Live M. pneumoniae inocula were
      grown in hamster serum-based medium in order to reduce the potential for the
      serum growth component to participate in the hyperaccentuated histopathological
      response as seen with challenge-rechallenge experiments which have used horse
      serum-based growth media. Despite the use of homologous animal serum, an early
      hyperaccentuated response occurred (day 3 score 13.3 vs day 10 score 7.7; P =
      0.02) which included perivascular infiltrates, and histopathological scores for
      early (day 3) and late (day 10) disease were similar (P > 0.10) between
      experiments of challenge-rechallenge when either homologous or heterologous sera
      were used in inoculum growth media. Parenteral vaccination with heat-killed
      bacteria also led to an early hyperaccentuated histopathological response after
      live respiratory challenge (scores on day 3: vaccinated 18.3, unvaccinated 6.2; P
      < 0.01) and this response was not significantly diminished when inocula were
      cleaned of growth medium components. An early accentuated response did not follow
      oral vaccination with heat-killed bacteria (score on day 3: vaccinated 5.7) and
      the late reaction was significantly less after challenge (scores on day 10:
      vaccinated 10.3, unvaccinated 14.6; P = 0.011). Studies of parenteral vaccination
      should include analyses for early disease after live challenge. Oral vaccination
      offers a promising route for stimulating protective immunity while minimizing
      undesirable recall immune events.

PMID- 8994327
TI  - Different exercise performance between aged patients with syndrome X and those
      with coronary artery disease.
AB  - BACKGROUND: Both patients with coronary artery disease (CAD) and those with
      syndrome X (anginal chest pain, exercise-induced myocardial ischemia, normal
      coronary angiogram and no evidence of coronary spasm) have ischemic
      electrocardiogram (ECG) during exercise. However, the difference of ECG change
      during treadmill exercise test in these two patient groups has rarely been
      studied. METHODS: In this prospective study, we evaluated and compared the
      changes of hemodynamics and 12-lead ECG during treadmill exercise test by
      modified Bruce protocol in 29 patients with syndrome X and 46 patients with CAD.
      RESULTS: As compared with CAD patients, syndrome X patients had significantly
      higher heart rate, higher systolic blood pressure and higher rate-pressure
      product at 1mm ST depression and peak exercise. The time to 1mm ST depression
      (304 +/- 128 vs 254 +/- 92 seconds, p = 0.06) and total exercise duration (463 +/
      108 vs 331 +/- 111 seconds, p < 0.001) were also longer in syndrome X than in
      CAD patients. However, coronary flow reserves, obtained from 20 syndrome X
      patients and 9 CAD patients, did not differ between both groups. (2.3 +/- 0.6 vs
      2.5 +/- 0.6, p = NS) CONCLUSIONS: Patients with syndrome X had higher ischemic
      threshold and better exercise tolerance than CAD patients though coronary flow
      reserve was similar between them. During exercise, more work-load as well as
      metabolic demands was required for the development of similar degree of
      myocardial ischemia in these aged syndrome X patients as compared with CAD
      patients.

PMID- 8994328
TI  - Examination of pericardial effusions by cytology and immunocytochemistry.
AB  - BACKGROUND: Cytologic examination of pericardial effusions (PE) has been
      uncommonly reported in the literature. Fewer reports have studied the role of
      immunocytochemistry in diagnosis of PE. We described our experience, according to
      cytologic examination and immunocyto-chemical staining of PE. METHODS: Over a
      four-year period, 50 PE specimens from 36 patients were examined cytologically by
      Wright-Giemsa stain and/or Papanicolaou stain, at Tri-Service General Hospital.
      Immunocytochemical stainings were further performed to ensure the cell nature.
      RESULTS: Eighteen of these patients had benign etiologies; the others suffered
      from malignant diseases. Sixteen cases, including eight benign and eight
      malignant, received pericardial biopsy for comparison. Commonly encountered cells
      in PE with any kind of etiology included neutrophils, lymphocytes macrophages and
      mesothelial cells. Cancer cells were additionally seen in malignant PE, but not
      in all cases with cancers. Furthermore, reactive mesothelial cells and
      macrophages were sometimes not easily distinguished from cancer cells, and
      reactive lymphocytes frequently mimicked hematopoietic malignancies. Further, the
      nature of small round tumor cells can hardly be ensured by morphologic
      examination only. Immunocytochemical studies were successfully used to solve
      these dilemmas in some suspicious cases. CONCLUSIONS: This study showed that
      cytology together with clinical information and immunocytochemistry can achieve
      excellent sensitivity and specificity in identification of malignant PE. The use
      of immunocytochemistry can even ensure the nature of certain cancers such as
      small cell carcinoma and B cell lymphoma.

PMID- 8994329
TI  - Carcinoid tumors of the gastrointestinal tract in Chinese of Taiwan: an analysis
      of fifty cases.
AB  - BACKGROUND: Gastrointestinal carcinoids are uncommon and potentially
      metastasizing neoplasms. Many series have been reported but few of them concern
      Chinese people. In this paper we present data on 50 Chinese with gastrointestinal
      carcinoids, living in Taiwan, to analyze their clinical features and prognostic
      factors. METHODS: From 1971 to 1995, 50 Chinese patients with primary
      gastrointestinal carcinoids were seen at Veterans General Hospital-Taipei. All
      patients had pathological proof of carcinoids. RESULTS: There were 35 males and
      15 females with a mean age of 55.9 +/- 2.1 years (range 20-76). The primary sites
      of the tumors, in order of frequency, were rectum (66%), duodenum (14%), stomach
      (8%), appendix (4%), ileum (4%), colon (2%) and cecum (2%). The cumulative 5-year
      survival rate was 73%. Carcinoids > or = 2cm in diameter were more frequently
      symptomatic and metastatic, and tended to have a lower survival rate than those <
      2cm in diameter (p = 0.06). Carcinoids which had invaded the serosa were more
      frequently symptomatic and metastatic, and had a lower survival rate than
      intramural carcinoids (p < 0.05). CONCLUSIONS: Rectal carcinoids were the most
      common gastrointestinal carcinoids in the Chinese living in Taiwan. Carcinoids >
      or = 2cm and carcinoids invading the serosa correlated well with symptom
      presentations and metastases. Intramural carcinoids had a better prognosis than
      carcinoids invading the serosa. Carcinoids < 2cm was a potentially positive
      factor of prognosis.

PMID- 8994330
TI  - Correlation of toxic signs, ultrasonographic findings and pathological changes in
      cholecystitis.
AB  - BACKGROUND: Cholecystitis is a frequently encountered clinical problem. What
      parameters are reliable in helping predict its severity? METHODS: One hundred and
      forty-nine cholecystectomized cases of cholecystitis were analysed of which 99
      (95 calculous) cases were pathologically diagnosed as chronic cholecystitis and
      50 acute (43 calculous) cholecystitis. Medical records were reviewed to determine
      the frequency of toxic signs. Sonographic findings (performed within three days
      prior to operation), and final pathological changes with respect to the thickness
      and echotexture of the gallbladder wall were compared. RESULTS: Of 99 chronic
      cholecystitis patients, 13 cases showed toxic signs. Sonography detected an
      abnormal wall in 64, but made a correct diagnosis in only 34 cases. A great
      discrepancy was found in wall thickness as measured by sonography and pathology.
      A discrepancy > or = 2mm was noted in 19 cases. Of 50 patients with acute
      cholecystitis (20 cases had complications, defined as severe acute
      cholecystitis), 31 cases (14 of the 20 severe acute cases) showed toxic signs.
      Sonographic findings demonstrated an abnormal wall in 46 cases (19 of the severe
      acute cases) and an accurate diagnosis in 28 cases (13 of the severe acute
      cases). A difference in the measurement of gallbladder wall thickness > or = 2mm
      was noted in 26 patients. CONCLUSIONS: Clinical toxic signs and sonographic
      findings could not offer sufficient information to quickly identify
      lifethreatening gallbladder diseases.

PMID- 8994331
TI  - An add-on study of selegiline to Madopar in the treatment of parkinsonian
      patients with dose-related fluctuations: comparison between Jumexal and Parkryl.
AB  - BACKGROUND: To improve dose-related fluctuations in patients with Parkinson's
      disease, the efficacy of selegiline, a selective inhibitor of monoamine oxidase
      B, was determined. METHODS: Twenty parkinsonian patients were selected for a
      short-term, single-blind, cross-over trial. Each patient received one of the two
      brands of selegiline, Parkryl (Mei-Shih), 10 mg per day as an adjunct to Madopar.
      After a 6-week treatment period and a 4-week wash-out period, the treatment was
      switched to the other brand of selegiline, Jumexal (Labatec), for another 6
      weeks. RESULTS: Five patients dropped out of the study because of the development
      of intolerable dyskinesia, hallucination or agitation. The 15 patients that
      completed the study made a mild improvement in the total motor scores of the on
      period during both treatments of Parkryl (p < 0.01) and of Jumexal (p < 0.05).
      The recorded daily off-time decreased from 37.8% to 20.7% in the Parkryl group (p
      < 0.01), and to 21.0% in the Jumexal group (p < 0.01). CONCLUSION: Selegiline, as
      an adjunct therapy to Madopar, has a moderate effect in prolonging the duration
      of on-time in parkinsonian patients with dose-related fluctuations. Jumexal
      seemed to produce no greater effect than Parkryl.

PMID- 8994333
TI  - Risk factor analysis of patients with chronic hepatitis C in Taiwan.
AB  - BACKGROUND: Parenteral transmission is the major route for hepatitis C virus
      (HCV) infection. However, in western countries, 40% of patients with chronic
      hepatitis C have no apparent risk factor of HCV infection. This study was
      designed to investigate the possible risk factors of HCV transmission in chronic
      hepatitis C patients in Taiwan. METHODS: One hundred and sixty-one consecutive
      patients with chronic hepatitis C and 161 age- and sex-matched healthy subjects
      were enrolled. Risk factors, including blood transfusion, injection with
      nondisposable needles, education status, surgery, dental procedure, tattooing,
      ear-piercing, sexual behavior and alcoholism, were obtained in every patient
      through questionnairing and interviewing. RESULTS: Patients with chronic
      hepatitis C, compared with healthy controls, had significantly higher rates of
      previous history of blood transfusion, frequent nondisposable needle injections,
      and lower education status (43.5% vs. 10.6%, 19.9% vs. 6.2%, 42.2% vs. 23.0%,
      respectively, all p < 0.05). Univariate logistic regression analysis showed blood
      transfusion, frequent nondisposable needle injections and low education as
      significant risk factors of HCV infection (all p < 0.05). Multivariate analysis
      again revealed them all to be independent significant risk factors associated
      with HCV infection in chronic hepatitis C patients. CONCLUSIONS: Parenteral
      transmission of HCV via transfusion and frequent nondisposable needle injections
      were the main routes of contracting HCV infection in patients with chronic
      hepatitis C in Taiwan. Also, people with low education ran the higher risk of
      transmission by HCV. Meticulous screening of the transfused blood for HCV, usage
      of disposable needles, and mass public education are important in our efforts to
      decrease chronic HCV infection in Taiwan.

PMID- 8994332
TI  - Mature cystic teratoma of the ovary: a clinicopathologic study of 283 cases.
AB  - BACKGROUND: Although in the English literature, much has been published about
      ovarian teratoma, no large series has been reported in Taiwan. Therefore a
      retrospective study of 283 consecutive cases of mature cystic teratomas of the
      ovary, operated at National Taiwan University Hospital between 1988 and 1993, was
      undertaken. METHODS: This series was based on a retrospective chart study at the
      Department of Obstetrics and Gynecology of the National Taiwan University
      Hospital from 1988 to 1993. All cases included in this study were proven by
      pathology review. The clinical data, pathology and complications are summarized.
      RESULTS: The incidence of mature cystic teratoma was 32.6% of primary ovarian
      neoplasm. As for the age distribution, the youngest patient was 12 years old and
      the oldest, 76. The largest number of cases was found in patients between the
      ages of 20 and 30 years; the mean age was 35.4 years. Pain, the most common
      complaint, was noted in 48.1% of the cases in whom it varied from a dull ache to
      the sharp, stabbing pain of torsion. Of greater interest was an unexpectedly high
      incidence (16.6%) of asymptomatic cysts found on routine physical examination.
      The right ovary was involved in 51.2%, the left ovary in 40.6% and bilateral
      ovaries were involved in 8.2%. The incidence of torsion was 9.2%, and was the
      highest in all complications. Ten concurrent pregnancies were noted, an incidence
      of 3.5%. The incidence of malignant transformation was 0.7%, with a pathology of
      squamous cell carcinoma. CONCLUSIONS: Mature cystic teratom is the most common
      germ cell tumor and accounts for about 33% of all ovarian neoplasm They occur
      primarily during the reproductive years, but may occur in the postmenopausal
      period or in childhood. A cystic teratoma can undergo malignant transformation;
      it occurs most frequently in postmenopausal women, and the prognosis is poor.
      However, it is a rare complicaiton, with an incidence less than 1%.

PMID- 8994334
TI  - Langerhans' cell histiocytosis (histiocytosis-X) in a women with typical
      ultrastructure of Birbeck's granule: a case report.
AB  - A 28-year-old woman was admitted to our hospital with the chief complaint of
      progressive gingival swelling with easy bleeding and loosening of teeth for about
      two years. The liver and spleen were not enlarged and there were no
      lymphadenopathy. The hemogram was normal. The skull X-ray showed floating teeth.
      CT scan of face showed destructive bony lesions over maxilla and left mandible
      with adjacent soft tissue swelling. Pathologic examination of the gingiva
      revealed that the oral mucosal tissue was heavily infiltrated with histiocyte
      like Langerhans' cells. The Langerhans' cells showed positive immunostain for S
      100 protein. Under electron microscope, ultrastructure of the Langerhans' cells
      revealed typical intracytoplasmic tennnis racquet-shaped structure with a central
      zipper-like striation (Birbeck's granules). Langerhans' cell histiocytosis was
      diagnosed. She received rdiotherapy with a total dose of 1,000 cGy in fractions
      and oral chemotherapeutic drugs. Painful gingival swelling subsided gradually.
      She was followed at our OPD for the past 10 months and there was no evidence of
      local recurrence. Langerhans' cell histiocytosis is a rare disease. The relevant
      literature about its distinct pathologic features, clinical course and treatment
      is reviewed.

PMID- 8994335
TI  - Adult Wilms' tumor: a case report.
AB  - Wilms' tumor (nephroblastoma) is the most common intraabdominal tumor in
      children; its three primary components are blastemal, epithelial and stromal,
      with predominance of tri-phasic lesion. The tumor is rare in adults, in whom the
      Wilms' tumor accounts for less than 1%. The case presented here concerns a case
      of 46-year-old female with stage II, Wilms' tumor, composed of purely mono-phasic
      differentiated epithelial component with favorable histology. The patient
      received radical nephrectomy, than post-operative chemotherapy and radiotherapy
      as recommended by National Wilms' Tumor Study. With the advent of modern
      chemotherapy, the adult Wilms' tumor can have a better prognosis than previously.
      Because of the rarity of adult Wilms' tumor and its unusual histo-morphology,
      this case is described and the literature, reviewed.

PMID- 8994336
TI  - Postcoital hemoperitoneum without identifiable bleeding source: a case report.
AB  - Spontaneous intra-abdominal bleeding has been called abdominal apoplexy. It has
      been so named because its nature and spontaneity closely resemble those of its
      more common cerebral counterpart. The bleeding source commonly came from a
      ruptured branch of celiac axis or superior mesenteric artery. Rarely,
      hemoperitoneum occurs spontaneously post coitus without evident vaginal injury.
      There were only twelve cases reported in the medical literature to date. Nearly,
      all of them showed injury of pelvic organs including round or broad ligaments,
      ovarian cysts or adhesion bands. A case of massive hemoperitoneum after coitus,
      with no definite bleeding source, is reported.

PMID- 8994337
TI  - The suitable treatment for adenocarcinoma in situ of uterine cervix: a report of
      four cases.
AB  - Adenocarcinoma in situ (AIS) of the uterine cervix is a rare disease. Some
      authors suggested that conization is a suitable treatment for AIS as for squamous
      cell carcinoma in situ. However, others did not agree. Four cases of AIS, from
      1984 to 1994, have been diagnosed in the Hospital of National Taiwan University.
      If the diagnosis of the conization specimen showed AIS, abdominal total
      hysterectomy was performed days thereafter. The remaining uterine cervix was
      checked by histopathology to determine whether it was free of cancer lesions. AIS
      lesions remained in the uterine cervix, as shown by conization in two cases. AIS
      is not like lesion as squamous cell carcinoma in situ lesion which is easy to be
      removed by conization. It is suggested that conization is not an adequate
      treatment for AIS, rather, a total hysterectomy should be performed.

PMID- 8994338
TI  - Electrophysiological studies on acute tetrodotoxin poisoning: a case report.
AB  - Tetrodotoxin (TTN) is a marine neurotoxin that is sometimes responsible for the
      mortality of pufferfish consumers. A case of human tetrodotoxication caused by
      ingestion of Goby is reported. The patient developed perioral numbness,
      acroparesthesia, generalized weakness and respiratory failure within hours after
      ingestion. The electrophysiological studies at the 16th hour of intoxication
      revealed generalized sensorimotor axonopathy, but no disturbance on the
      neuromuscular junction motor endplate. Human electrophysiological studies of
      acute TTX intoxication have rarely been documented in literature.

PMID- 8994339
TI  - Cystic meningioma in children: a case report.
AB  - The case of a child with a cystic meningioma is reported, along with a review of
      25 cases from the literature. Cystic change is more common in infants in the
      first year of life. Eleven of the 26 cystic tumors were in infants. More than
      half of the cystic meningiomas in adults are meningotheliomatous, while that is
      the least common subtype in children. Complete removal of the cyst wall is
      necessary in the intratumoral type to prevent recurrence.

PMID- 8994341
TI  - [Biochemical and pharmacological studies of Clostridium perfringens epsilon
      toxin].

PMID- 8994340
TI  - [Characterization of virulence factors of mutans streptococci and specific
      inhibition of these factors].

PMID- 8994342
TI  - [Properties and action of Bordetella dermonecrotizing toxin].

PMID- 8994343
TI  - [Mechanisms of bacterial resistance to quinolones].

PMID- 8994344
TI  - [Exotoxins of Bacillus cereus associated with food poisoning].

PMID- 8994345
TI  - [Morphology of micro-organism--development of my electron microscopical study].

PMID- 8994347
TI  - [Stress response of pathogenic bacteria--are stress proteins virulence factors?].

PMID- 8994346
TI  - [Genetically strange Borrelia and conservation of genes associated with motility
      in Lyme disease Borrelia].

PMID- 8994348
TI  - [Molecular epidemiology of infections with enterohemorrhagic Escherichia coli
      O157 in Japan, 1996].

PMID- 8994349
TI  - [Production of free bile acids by bacterial deconjugation from conjugated bile
      acids derived from peptone in a medium].
AB  - In the course of studies of in vitro bile acid transformation by lactic acid
      bacteria, we noticed that the medium used contained conjugated bile acids. HPLC
      analysis of the medium for each component indicated that these bile acids had
      originated from a peptone (Bacto Peptone, Difco). The concentration of these bile
      acids in a medium containing 2% Bacto Peptone was greater than 200 microM, higher
      than the concentration of bile acids usually added in in vitro bile acid
      transformation studies. Therefore, in such studies, it would be necessary to
      distinguish between the production of free secondary bile acids by bacterial
      deconjugation and that by 7 alpha-dehydroxylation. Since bile acids affect not
      only bacterial growth but also many metabolic activities, particular attention
      should be given to the use of Bacto Peptone in the medium.

PMID- 8994350
TI  - [An improved phagocytic plaque method using gram-negative bacilli].
AB  - The phagocytic plaque method developed for evaluation of the phagocytic function
      of leukocytes is not only very useful but convenient for both basic and clinical
      investigations. So far, only Staphylococcus aureus has been demonstrated to give
      clear phagocytic plaques. In this study, we successfully obtained clear
      phagocytic plaques with gram-negative bacilli (Pseudomonas aeruginosa and
      Escherichia coli). The plaques given by E. coli were morphologically nearly the
      same as those by S. aureus, whereas those of P. aeruginosa were elongated.

PMID- 8994351
TI  - Positional determination of the naso-temporal retinal axis coincides with
      asymmetric expression of proteins along the anterior-posterior axis of the eye
      primordium.
AB  - We used two different methodologies to examine at what stage development retinal
      positional specificity is established and which molecules are responsible. The
      first goal was achieved by removing parts of the presumptive temporal primary
      optic vesicle at stage 11 (40 to 45 hr of incubation) and fate mapping of tissue
      with presumptive nasal properties that shifted into the wound during the events
      of wound-healing. Participation of the shifted tissue in the healing resulted in
      assembly of a temporal retina with mosaic-like projection properties, as examined
      by retrograde double staining of the retinal ganglion cells from the optic
      tectum. In addition to cells with normal temporal-rostral projections, clusters
      of ganglion cells with nasal-like projection identities appeared labelled within
      the temporal hemiretina. The number of clusters increased with the amount of
      resected tissue, and by almost complete ablation of the presumptive temporal
      anlage, a temporal hemiretina with predominantly nasal retinotectal specificity
      was created. These neuroanatomical results suggested that neuroepithelial cells
      had fixed nasal and temporal positional specificities at stage 11. To examine
      differences in the cells derived of either half of the eye cup, we performed
      biochemical one- and two-dimensional gel electrophoresis of the hemianlagen at
      stage 11. In addition, incorporation of 35S-methionin into newly synthesized
      peptides was investigated. Both techniques revealed the exclusive expression of
      one major and three less-abundant proteins within the presumptive nasal anlage.
      The most abundant of these proteins has a molecular weight of about 40 kDa and is
      clearly distinguishable both in gel electrophoresis and autoradiography. The
      asymmetric protein patterns had disappeared when the retina was analysed with the
      same methods at the more advanced embryonic days E4 and E6. The asymmetry in the
      expression of proteins in the retinal primordium may be the biochemical correlate
      of an early positional specification of the retinal neuroepithelium. The
      difference in the protein expression may explain that mixing the positionally
      specified cells of either origins results in projection mosaics.

PMID- 8994352
TI  - Control of Drosophila opsin gene expression by carotenoids and retinoic acid:
      northern and western analyses.
AB  - In the fly, thorough retinoid deprivation is possible, to optimize investigation
      of the effects of vitamin A metabolites and retinoic acid (RA) on visual
      development. Retinoids had been found to control fly opsin gene transcription,
      though this finding was contested. Northern blots on Drosophila heads showed that
      mRNA of Rh1 (the predominant rhodopsin) was high in vitamin A replete controls,
      very low in deprived flies, and increased upon feeding carrot juice to deprived
      flies as early as 1 hr. Expression of the ribosomal protein 49 [rp49] gene (the
      control) was equal both in deprivation and in replacement. Recovery of Rh1
      protein upon such carotenoid replacement followed, barely detectable on Western
      blots at 4 hr but conspicuous by 8 hr. Alternative chromophore deprivation with
      yeast-glucose food yielded flies with opsin mRNA on Northerns but not rhodopsin,
      as demonstrated by Western blots, spectrophotometry and the electroretinogram
      (ERG). Rh1's mRNA but not Rh1 protein resulted from rearing flies from egg to
      adult on the otherwise deprivational medium supplemented with RA or beef brain
      heart infusion. By comparing results from these different media it was concluded
      that: [1] deprivation and replacement affect opsin gene transcription; and [2]
      contradictory conclusions were from chromophore deprivation which does not
      eliminate all retinoid dependent factors which could affect the opsin promoter.
      Preliminary evidence shows that carotenoid deprivation decreases two proteins
      relevant to visual function: [1] phospholipase C (PLC); and [2] Drosophila
      retinoid binding protein (DRBP).

PMID- 8994353
TI  - Inducible nitric oxide synthase in retinal ischemia-reperfusion injury.
AB  - The purpose of this study was to determine whether inducible nitric oxide
      synthase (iNOS) was implicated in the pathogenesis of retinal ischemia
      reperfusion injury. Semi-quantitative reverse transcription-polymerase chain
      reaction showed that the level of iNOS mRNA expression was markedly increased in
      rat retina following transient ischemia, with peak expression at 12 hr after
      reperfusion (15.7-fold increase over pre-ischemic levels). In situ hybridization
      showed that iNOS mRNA was expressed by resident retinal cells, most likely glial
      cells in the innermost retina, and also by the neutrophils that had infiltrated
      the retina. Intraperitoneal administration of NG-(1-iminoethyl)-L-ornithine (L
      NIO), an inhibitor of iNOS, significantly increased the rate of b-wave recovery
      compared to that of control animals. The values (mean +/- S.E.M.) were 55.0 +/-
      4.4% versus 40.1 +/- 5.1% (P < 0.05) at 1 day and 68.6 +/- 6.6% versus 45.8 +/-
      3.5% (P < 0.05) at 3 days. This study shows that iNOS mRNA is highly expressed by
      non-neuronal cells of the inner retina during reperfusion following transient
      retinal ischemia. It also shows that L-NIO treatment provides some protection
      against ischemia-reperfusion injury. We suggest that nitric oxide produced by
      iNOS may mediate retinal ischemia-reperfusion injury.

PMID- 8994354
TI  - Expression of vascular endothelial growth factor (VEGF) in retinoblastoma but not
      in posterior uveal melanoma.
AB  - All solid tumors must acquire a vascular stroma to grow beyond a minimal size.
      Vascular endothelial growth factor (VEGF) is a potent and specific angiogenic
      growth factor both in vitro and in vivo that may participate in the formation of
      the vascular tumor stroma. In the present study, we examined the expression of
      VEGF in the paraffin sections of 20 eyes harboring retinoblastoma or posterior
      uveal melanoma, but also in corresponding tumor cellines. By using in situ
      hybridization, we found that all but one of the retinoblastomas expressed VEGF
      mRNA. Particularly high expression was detected in areas of loosely packed tumor
      cells with prominent chromatin. By contrast, none of the posterior uveal
      melanomas expressed significant amounts of VEGF mRNA. Immunostaining with an
      antibody against VEGF confirmed that retinoblastomas, but not posterior uveal
      melanomas, also contained detectable VEGF protein. To further study the
      expression of VEGF in these tumor cells we performed Northern blotting on a
      retinoblastoma celline, Y79, and on an uveal melanoma celline, OM431. Both of
      these cellines expressed low levels of VEGF mRNA under normal culture conditions.
      However, when the cells were cultured under hypoxic conditions, a strong increase
      in VEGF mRNA could be seen in Y79 cells but not in OM431 cells. By using a
      bioassay, we also found that hypoxia stimulated the secretion of VEGF protein
      into the culture medium of Y79 cells. In conclusion, we have shown that VEGF mRNA
      and protein are expressed in retinoblastomas but not in posterior uveal
      melanomas. Moreover we have shown that VEGF is hypoxia-inducible in
      retinoblastoma cells. These results suggest that focal hypoxia may act as a
      stimulus for VEGF production in retinoblastomas, that in turn may contribute to
      tumor growth by stimulating the formation of a vascular stroma.

PMID- 8994356
TI  - Non-retinal abnormalities associated with progressive retinal atrophy (PRA) in
      the miniature poodle.
AB  - Osmotic fragility was examined in red blood cells taken from miniature poodles
      with progressive retinal atrophy (PRA). In this study, the median osmotic
      fragility for erythrocytes (concentration of NaCl required for 50% haemolysis)
      was found to be significantly lower for clinically affected, compared to
      unaffected animals. These differences were maintained regardless of changes in
      erythrocyte incubation pH (7.0, 7.5). There was no difference in the slope
      parameter of erythrocyte osmotic fragility profiles for both sets of animals,
      indicating a similar variability of erythrocyte age. In groups of animals
      maintained with the same diet and fasted for 12 hr, and in groups of animals with
      no dietary constraints, total plasma cholesterol was significantly lower for
      affected, compared to unaffected animals. Red blood cell indices were also
      assessed; mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), red
      blood cell count (RBC) and blood haemoglobin concentration (Hb) were normal,
      while erythrocyte packed cell volume (PCV) was significantly reduced for
      affected, compared to unaffected. Data from this study suggest that the abnormal
      erythrocyte osmotic fragility of affected animals is unlikely to be a consequence
      of a higher erythrocyte surface area/volume ratio, higher plasma cholesterol
      concentration, or greater proportion of new to old erythrocytes, and that a
      general membrane defect might be associated with prcd in the miniature poodle.

PMID- 8994355
TI  - Subthreshold UV radiation-induced peroxide formation in cultured corneal
      epithelial cells: the protective effects of lactoferrin.
AB  - Acute exposure to suprathreshold ultraviolet B radiation (UV-B) is known to cause
      photokeratitis resulting from the necrosis and shedding of corneal epithelial
      cells. however, the corneal effects of low dose UV-B in the environmental range
      is less clear. In this study, subthreshold UV-B was demonstrated to cause non
      necrotic peroxide formation in cultured corneal epithelial cells, which was
      attenuated by the major tear protein lactoferrin. Intracellular oxidative insults
      and cell viability of rabbit corneal epithelial cells (RCEC) were assessed by
      dual-color digital microfluorography using carboxydichlorofluorescin (CDCFH)
      diacetate bis (acetoxymethyl) ester, a hydroperoxide-sensitive fluoroprobe, and
      propidium iodide (PI), respectively. The magnitude of UV-induced oxidative
      insults was calibrated by concentrations of exogenously applied H2O2 which evoke
      compatible levels of CDCFH oxidation. Exposure of RCEC to low-dose UV-B (2.0 mJ
      cm-2 at 313 nm, 10.0 mJ cm-2 total UV-B) caused intracellular oxidative changes
      which were equivalent to those elicited by 240 microM hydrogen peroxide under the
      conditions of the study. The changes were dose dependent, non-necrotic, and were
      partially inhibited by lactoferrin (1 mg ml-1) but not by iron-saturated
      lactoferrin. Pretreatment with deferoxamine (2 mM) or catalase (100 U ml-1) also
      attenuated the UV-induced oxidative stress. The results indicate that UV-B
      comparable to solar irradiation levels causes significant intracellular peroxide
      formation in corneal epithelial cells, and that lactoferrin in tears may have a
      physiological role in protecting the corneal epithelium from solar UV
      irradiation.

PMID- 8994357
TI  - High galactose levels in vitro and in vivo impair ascorbate regeneration and
      increase ascorbate-mediated glycation in cultured rat lens.
AB  - In contrast to conventional view that glucose is the sole glycating agent,
      ascorbate has now emerged as a potential precursor of advanced glycation products
      in lenses during cataractogenesis, owing to the high concentration present in
      human lens. The effects of high hexose environment in vitro and in vivo on the
      disruption of redox equilibrium of ascorbate (ASA) to dehydroascorbate (DHA),
      which is required for ascorbate-mediated crystallin modification by the Maillard
      reaction during cataractogenesis were examined. Organ culture experiments were
      performed with rat lenses that were first exposed to high galactose levels in
      vitro and in vivo and then incubated with 1-14C-labeled ASA, DHA or DKG (2,3
      diketogulonic acid). Formation of ASA degradation products as a function of time
      was assessed by radiometric TLC method. Upon incubation with ASA or DHA, an
      elevated level of the degradation product, DKG, was detected in lenses exposed to
      galactose in vivo and in vitro. ASA uptake was significantly enhanced in the
      galactosemic lenses as compared to controls (P = 0.01). Regeneration of ASA from
      DHA in both galactose treated and galactosemic lenses was impaired when compared
      to control lens which completely converted DHA from the medium into ASA.
      Surprisingly, the galactose exposed lenses showed enhanced permeability to DKG
      which was picked up readily from the medium in contrast to normal healthy lenses
      which remained impermeable to DKG. Galactose exposed lenses both in vitro and in
      vivo showed a 5-9-fold increase in crystallin bound Schiff base-linked
      radioactivity when incubated with 1-14C-labeled ASA or DHA. As a preamble to the
      question of whether lens pigmentation predisposes towards ascorbate oxidation,
      lens homogenate from normal young and old pigmented cataractous lenses were
      incubated with [1-14C]ASA. After 2 days, ASA levels were found to have decreased
      by 74% and DKG levels increased by 48% in brunescent lens as compared to the
      young lens. These data demonstrated that profound abnormalities in ASA metabolism
      exist in lenses exposed to a high sugar environment suggestive of a breakdown of
      the redox equilibrium of ASA to DHA and a loss of membrane permeability barrier
      for DKG. The latter would further contribute toward a ASA-catalysed Maillard
      reaction in the redox impaired lens.

PMID- 8994358
TI  - Plasma membrane calcium-ATPase in cultured human retinal pigment epithelium.
AB  - The present work demonstrates the presence of plasma membrane (Ca(2+) + Mg2+)
      ATPase (PMCA) activity in cultured human retinal pigment epithelium (HRPE). Whole
      cell HRPE homogenates exhibited Ca(2+)-stimulated ATPase activity that was
      inhibited with high affinity (IC50 = 60 nM) by eosin, a potent inhibitor of the
      erythrocyte PMCA. This activity was not inhibited by thapsigargin, a selective
      inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA). A PMCA
      specific monoclonal antibody exhibited staining in attached HRPE monolayers. By
      Western blot analysis of SDS-PAGE separations of whole cell lysates of HRPE, this
      antibody identified a single band at approximately 145 kD. Finally, a Ca(2+)
      dependent, La(3+)-augmented phosphoprotein, which comigrated with anti-PMCA
      immunoreactivity, was also detected. Taken together, these results show that
      cultured HRPE express PMCA activity.

PMID- 8994359
TI  - Asymmetrical response of the intraluminal and extraluminal surfaces of the
      porcine retinal artery to exogenous adenosine.
AB  - The relative effects of exogenous adenosine applied intraluminally or
      extraluminally were compared on first-order pig retinal arteries in an isolated
      perfused artery preparation. First-order retinal arteries with at least one side
      branch were cannulated and perfused at a constant flow in an environmentally
      controlled organ bath on the stage of an inverted microscope. Vessels were
      precontracted with 10(-4) methoxamine applied extraluminally, which produced a
      sustained contraction. Then, either extraluminal or intraluminal adenosine was
      added in increasing concentrations from 10(-9) to 10(-3) M. During these
      procedures continuous measurements of external vessel diameter were made. The
      average external diameter of the retinal arterial segments used was 127.6 +/- 2.3
      microns (n = 13). Extraluminal methoxamine (10(-4) M) constricted the vessels to
      77.9 +/- 2.0% (n = 9) and 78.8 +/- 0.8% (n = 4) of the control value for the
      vessels later exposed to extraluminal and intraluminal adenosine respectively.
      Extraluminal adenosine caused a dose-dependent dilatation which commenced between
      10(-7) M and 10(-6) M, and reached a percentage dilatation of 22.6 +/- 1.8% (n =
      9) at 10(-3) M. For concentrations of 10(-4) M and above, spontaneous
      oscillations in diameter were observed for extraluminally-applied adenosine with
      an average period of 0.46 +/- 0.02 (n = 9) cycles per minute. The average
      percentage diameter oscillation was +/- 7.1% of the mean diameter. In contrast,
      intraluminal adenosine failed to cause dilatation or spontaneous oscillations at
      all concentration values, although the dilatory ability of these vessels was
      confirmed by intraluminal application of the Ca2+ channel blocker verapamil. In
      conclusion this study has demonstrated that the two sides of the retinal artery
      wall are differentially sensitive to adenosine, with the intraluminal route being
      ineffective. In vivo, in hypoxic or ischemic situations, adenosine is released by
      extraluminal neural tissue and minimizes tissue damage, partially by acting as a
      signaller of metabolic status to the vasculature leading to vasodilatation and
      hence increased local blood flow. This study shows that delivery of adenosine for
      therapeutic purposes through an intraluminal route is not a feasible proposition.
      This isolated, perfused artery technique has considerable potential to improve
      our understanding of uptake mechanisms, metabolism and vasoactivity of the
      retinal vessel wall.

PMID- 8994360
TI  - Effects of basic fibroblast growth factor on the retinal degeneration of the
      mi(vit)/mi(vit) (vitiligo) mouse: a morphologic and electrophysiologic study.
AB  - Basic fibroblast growth factor (bFGF) has been shown to rescue dying
      photoreceptor cells in the RCS rat, a model with a genetic defect of the RPE that
      impairs outer segment phagocytosis. The purpose of the present study was to
      determine whether intravitreal injection of bFGF would have a similar effect on
      photoreceptor cell death in the vitiligo (C57BL/6-mi(vit)/mi(vit)) mouse. This
      mutant mouse loses photoreceptor cells slowly over many months. Experimental
      evidence suggests that the primary cellular site of the defect is the RPE. In the
      present study, bFGF was prepared with and without heparin in PBS and injected
      intravitreally into vitiligo mice at ages 2, 4, 6, 8 and 13 weeks, surrounding
      the onset of photoreceptor cell death. Non-injected, PBS-injected and heparin/PBS
      injected mice served as controls. Scotopic ERG's were performed on one group of
      mice prior to killing. Mice were killed 4, 6 or 10 weeks following the injection
      and the eyes were processed for histology and analysed. The amplitude of the b
      wave was significantly smaller in mice injected with bFGF/PBS than in PBS
      injected and non-injected eyes regardless of the time of injection or duration
      following injection. Histological examination revealed that the number of rows of
      photoreceptor cells did not differ significantly between bFGF-injected, vehicle-
      or non-injected mice. Although slight improvement in the attachment of outer
      segments to RPE was observed in 4 week mutants injected with bFGF/heparin/PBS, a
      similar result was obtained in heparin/PBS injected mutants. In mice injected
      with bFGF without heparin, detachment was severe and gross disruption of neural
      retina was observed. There were significantly more macrophages and photoreceptor
      cells in the subretinal space in bFGF injected mice. It appears that at the
      dosages and times administered, bFGF does not improve the electrophysiological
      functioning of the retina nor retard the degeneration of the retina in the
      vitiligo mouse as it does in the RCS rat.

PMID- 8994361
TI  - Distribution of SPARC protein (osteonectin) in normal and wounded feline cornea.
AB  - The purpose of this study was to determine the distribution of SPARC protein,
      also known as osteonectin or BM-40, in normal and wounded cat cornea. Indirect
      immunohistochemistry was used to study the distribution of SPARC protein. The
      following types of corneal wounds were performed: -5.0-dioptric excimer laser
      photorefractive keratectomy, mechanical keratectomy, and epithelial scrape
      wounds. The cats (n = 9) were killed 1-30 days after the operation and corneas
      prepared for immunohistochemistry using polyclonal rabbit anti-murine SPARC
      antibody and avidin-biotin complex. Weak immunoreaction for SPARC protein was
      observed in the cytoplasm of epithelial and endothelial cells but not in the
      keratocytes of both normal and wounded corneas. Unwounded extracellular matrix
      was negative in the control cornea. Following experimental wounding, an intense
      immunoreaction for SPARC appeared transiently at the basal aspect of the basal
      epithelial cells of multilayered, recently healed epithelium. The SPARC
      immunoreaction began from the wound edge but was not observed subjacent to the
      flattened single-layered epithelial cells of the leading edge. The immunoreaction
      for SPARC was found on Days 1-6 following wounding and subsequently withdrew. The
      transient appearance of SPARC under the healing corneal epithelium suggests its
      involvement in the regulation of epithelial cell migration or shape during the
      healing process.

PMID- 8994362
TI  - Increase in the intramolecular disulfide bonding of alpha-A crystallin during
      aging of the human lens.
AB  - Aging of the normal human lens is accompanied by oxidation of protein sulfhydryl
      groups to disulfide groups. Although this has been known for many years, very
      little is known about the exact amino acid residues involved. In addition, almost
      nothing is known concerning the temporal sequence of this oxidative process over
      the lifetime of the individual. To address these two concerns for alpha-A
      crystallin, the polypeptide was purified from total proteins of the human lens,
      followed by digestion with lys-C endoprotease. Mass spectral analysis of the
      resulting fragments demonstrated that the two cysteine residues (cysteine-131 and
      cysteine-142) are present as a mixture of an intramolecular disulfide bond and
      free sulfhydryl groups. Reverse phase chromatography was used to resolve and
      quantitate the relative amounts of the two forms present in alpha-A crystallin
      from normal lenses of different age. Even in very young lenses (4 months and 5
      months of age) there is significant oxidation of the two cysteine residues.
      However, the oxidative state of these two residues does not significantly change
      during the next approximately 27 years of age, after which there is an increase
      in the relative amount of intramolecular disulfide bonding. Together, these
      results have identified and quantitated the relative change in the oxidative
      state of two specific cysteine residues of alpha-A crystallin in human lenses of
      different age, and have established that age-dependent oxidation of these two
      residues occurs primarily during the later part of life.

PMID- 8994363
TI  - Transglutaminase involvement in UV-A damage to the eye lens.
AB  - Solar radiation is believed to be one of the major environmental factors involved
      in lens cataractogenesis. The purpose of the study was to investigate the
      mechanisms by which UV-A at 365 nm causes damage to the eye lens. Bovine lenses
      were placed in special culture cells for pre-incubation of 24 hr. The lenses were
      positioned so that the anterior surface faced the incident UV-A radiation source
      and were maintained in the cells during irradiation. After irradiation, lens
      optical quality was monitored throughout the culture period and lens epithelium,
      cortex and nuclear samples were taken for biochemical analysis. Transglutaminase
      activity in the lens was affected by the radiation. The activity of
      transglutaminase in lens epithelium cortex and nucleus increased as a result of
      the irradiation and then declined towards control levels during the culture
      period, as the lens recovered from the UV-A damage. Specific lens proteins, alpha
      B and beta B1 crystallins (the enzyme substrates) were analyzed by SDS
      polyacrylamide gel electrophoresis and immunoblotting with specific antibodies.
      Seventy-two hours after irradiation of 44.8 J cm-2 UV-A, alpha B crystallins were
      affected as was shown by the appearance of aggregation and degradation products.
      Some protein changes seem to be reversible. It appears that transglutaminase may
      be involved in the mechanism by which UV-A causes damage to the eye lens.

PMID- 8994364
TI  - Splice variants of arrestins.

PMID- 8994365
TI  - Preferential rod and cone photoreceptor abnormalities in heterozygotes with point
      mutations in the RDS gene.

PMID- 8994367
TI  - Policy. Medical emergencies on the fly.

PMID- 8994366
TI  - Finance ... the hospital field keeps shrinking.

PMID- 8994368
TI  - Managed care ... alternative medicine.

PMID- 8994369
TI  - Consumers. All in the family.

PMID- 8994370
TI  - Insurance ... problems getting health care or paying for it.

PMID- 8994371
TI  - Pharmaceuticals ... FDA takes too long to approve new drugs and equipment.

PMID- 8994372
TI  - Quality watch ... yardsticks for measuring quality are turning up everywhere.

PMID- 8994373
TI  - Human resources ... health care professionals who work in ambulatory and home
      health care are getting paid more.

PMID- 8994374
TI  - Internet ... isn't just for geeks anymore.

PMID- 8994375
TI  - Target practice. In California and elsewhere, state officials are taking shots at
      hospital sales to for-profits.

PMID- 8994376
TI  - Dollars & death. Money changes everything. Now it's entering the debate over the
      right to die--with explosive results.
AB  - Physician-assisted suicide is out of the shadows--a raging debate being carried
      all the way to the Supreme Court. But what role does money play for people who
      ask their doctors for help in hastening death? An increasingly potent one, say
      alarmed ethicists and scholars.

PMID- 8994377
TI  - Air supplies. By shipping--even flying--medical products from regional hubs,
      hospitals pursue big savings.

PMID- 8994378
TI  - Antisense targeting in behavioural neuroendocrinology.

PMID- 8994379
TI  - Investigation of the effects of antisense oligodeoxynucleotides to islet amyloid
      polypeptide mRNA on insulin release, content and expression.
AB  - We have investigated the effects of antisense oligodeoxynucleotides (oligos) to
      islet amyloid polypeptide (IAPP) mRNA on the expression and secretion of IAPP and
      insulin, in the clonal beta-cell line HIT-T15. Phosphorothioate-modified oligos
      were cytotoxic compared with phosphodiester (D)-oligos. Of the nine oligos tested
      using a lipofection reagent, O3, a 30-mer D-oligo complementary to a sequence
      downstream of the IAPP initiation codon, showed a significant dose-dependent
      suppression of IAPP mRNA, with a 42% decrease at 7.5 microM, compared with a
      scrambled (MSO3) control oligo (n = 3, P < 0.01). A subsequent 89% suppression of
      IAPP release was observed in the 4-h period following antisense treatment (1.78
      +/- 0.13 (MSO3) vs 0.19 +/- 0.14 (O3) pmol/10(6) cells per 240 min, n = 7, P <
      0.01). A significant increase in insulin mRNA (100 +/- 10% (MSO3) vs 124 +/- 8%
      (O3), n = 3, P < 0.05) and insulin content (13.0 +/- 0.9 (MSO3) vs 17.4 +/- 1.4
      (O3) pmol/10(6) cells, n = 7, P = 0.028) was observed following treatment with O3
      at 7.5 microM. O8, a 20-mer D-oligo directed to a region of IAPP mRNA further
      downstream than O3, also showed a decrease in IAPP mRNA and peptide release and
      an increase in insulin content. No significant changes were observed in the
      expression and release of the unrelated beta-cell peptide, neuropeptide Y. We
      thus show a suppression of synthesis and release of IAPP in HIT-T15 cells using
      antisense oligos. The associated increase in insulin mRNA and content in these
      cells after treatment with IAPP antisense oligos is in accord with an inhibitor
      action of IAPP on insulin availability.

PMID- 8994381
TI  - Cryptic peptides of prepro-TRH antagonize TRH-induced GH secretion in chickens at
      extrapituitary sites.
AB  - Complete processing of the TRH precursor in the rat hypothalamus generates TRH
      and a number of other "cryptic' peptides that flank the TRH progenitor sequences.
      Two of these peptides, P4 (Ser-Phe-Pro-Trp-Met-Glu-Ser-Asp-Val-Thr; present
      between amino acids 160 and 169 of rat prepro-TRH) and P5 (Phe-Ile-Asp-Pro-Gly
      Leu-Gln-Arg-Ser-Trp- Glu-Glu-Lys-Glu-Gly-Glu-Gly-Val-Leu-Met-Pro-Glu; present
      between amino acids 178 and 199 of rat prepro-TRH), have recently been shown to
      modulate TRH-induced GH and thyrotrophin release from rat pituitary glands. The
      possibility that these peptides might modulate GH secretion in chickens was
      examined, since TRH is a physiological GH-releasing factor in birds. The
      administration of P4 and P5 (at doses of 10 and 100 micrograms/kg) consistently
      lowered basal plasma GH concentrations 30 and 60 min after a bolus i.v.
      injection. Pretreatment with P4 and P5 similarly suppressed the GH response to
      systemic TRH challenge. The GH-releasing activity of maximally stimulatory doses
      of TRH was also reduced by concomitant injections of either P4 (100
      micrograms/kg) or P5 (100 micrograms/kg), which blocked the GH-releasing activity
      of submaximally effective doses of TRH. In marked contrast, neither P4 nor P5
      significantly affected basal or TRH-induced GH release from chicken pituitary
      glands incubated in vitro. These results demonstrate novel actions of P4 and P5
      on hypothalamic-pituitary function and, for the first time, indicate
      extrapituitary sites of action for these cryptic peptides in modulating anterior
      pituitary function.

PMID- 8994380
TI  - Mechanisms of amino acid-induced insulin secretion from the glucose-responsive
      BRIN-BD11 pancreatic B-cell line.
AB  - The effects of different classes of amino acids known to be transported and
      utilized by pancreatic B-cells were examined using the novel glucose-responsive
      pancreatic B-cell line, BRIN-BD11. Amino acids tested included alpha
      aminoisobutyric acid, L-alanine, L-arginine, L-glutamine, glycine, L-leucine, L
      lysine, L-proline and L-serine. At non-stimulatory (1.1 mmol/l) glucose, acute
      incubations with either 1 or 10 mmol/l amino acid evoked 1.3- to 4.7-fold
      increases of insulin release. Raising glucose to 16.7 mmol/l enhanced the effects
      of all amino acids except L-glutamine, and increased insulin output at 10 mmol/l
      compared with 1 mmol/l amino acid. Glyceraldehyde (10 mmol/l) also served to
      promote 10 mmol/l amino acid-induced insulin secretion with the exceptions of L
      arginine, glycine, L-lysine and L-proline. At 16.7 mmol/l glucose, diazoxide (300
      mumol/l) significantly decreased the secretory response to all amino acids except
      L-glutamine. Likewise, verapamil (20 mumol/l) or depletion of extracellular Ca2+
      reduced insulin output indicating the importance of Ca2+ influx in the actions of
      amino acids. These data indicate that BRIN-BD11 cells transport and utilize amino
      acids, acting in association with glycolysis, K(+)-ATP channels and/or voltage
      dependent Ca2+ channels to promote Ca2+ influx and insulin secretion. The
      response of BRIN-BD11 cells to glucose and amino acids indicates that this is a
      useful cell line for future research on the mechanisms of nutrient regulation of
      insulin secretion.

PMID- 8994382
TI  - Insulin-like growth factor I enhancement of steroidogenesis by bovine granulosa
      cells and thecal cells: dependence on de novo cholesterol synthesis.
AB  - Studies were conducted to determine the importance of de novo cholesterol
      synthesis and cholesterol side-chain cleavage enzyme in the action of IGF-I in
      bovine granulosa and thecal cells. Granulosa and thecal cells from bovine
      follicles were cultured for 2 days in 10% fetal calf serum and then treated with
      luteinizing hormone (100 ng/ml) and IGF-I (0 or 100 ng/ml) for an additional 2
      days in serum-free medium. During the last 24 h of treatment, cells were
      concomitantly treated with simvastatin (0, 0.5 or 5 micrograms/ml) or 25
      hydroxycholesterol (0 or 10 micrograms/ml). Simvastatin, a potent inhibitor of
      the key enzyme controlling de novo cholesterol synthesis, 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase, completely inhibited (P < 0.05)
      progesterone production by granulosa cells and progesterone and androstenedione
      production by thecal cells. Simvastatin also inhibited (P < 0.05) granulosa cell
      and thecal cell proliferation. Concomitant treatment with mevalonate, an
      immediate product of HMG-CoA reductase, attenuated the inhibitory effect of
      simvastatin on progesterone and androstenedione production by thecal cells and
      blocked the inhibitory effect of simvastatin on cell proliferation. The addition
      of 25-hydroxycholesterol, a substrate for cholesterol side-chain cleavage enzyme,
      had no effect (P > 0.10) on IGF-I-stimulated progesterone or androstenedione
      production by thecal cells and actually inhibited (P < 0.05) IGF-I-stimulated
      progesterone production by granulosa cells. These results provide indirect
      evidence indicating that stimulation of HMG-CoA reductase is an important locus
      of IGF-I action in bovine granulosa and thecal cells, whereas IGF-I has little or
      no effect on side-chain cleavage enzyme activity in these same cell types under
      the culture conditions employed.

PMID- 8994384
TI  - Repartitioning of maternal muscle protein towards the foetus induced by a
      polyclonal antiserum to rat GH.
AB  - Growth and protein accretion were studied in maternal muscle and liver and in
      foetuses of rats on day 20 of pregnancy. In young rats, weighing 120 g at mating,
      muscle mass and protein content of three hind-limb muscles, soleus, plantaris and
      gastrocnemius, increased on average by 7% compared with non-pregnant controls
      although the rate of muscle protein synthesis was decreased. In mature rats,
      rates of muscle protein synthesis were also reduced on day 20 of pregnancy but no
      change in muscle mass was observed. Rates of liver protein synthesis and
      accretion were increased in the pregnant animals; the effect was larger in the
      young pregnant rat. Administration of an antibody to rat GH (anti-rGH) for 10
      days to young pregnant rats reversed the effect on the same three maternal
      muscles and resulted in a 9-11% lower muscle mass and protein content, compared
      with control pregnant animals. In both young and mature dams serum IGF-I
      concentrations were halved on day 20 of pregnancy, a further small reduction was
      observed in response to anti-rGH. No significant change in serum insulin or
      corticosterone levels was observed. Anti-rGH treatment also reduced food intake
      but foetal weight at 20 days was significantly increased (14%). The effects on
      maternal muscle were not the result of loss of appetite associated with anti-GH
      administration as, in rats pair-fed to the intake of the anti-rGH group, maternal
      muscle and foetal weights were the same as in animals with food available ad
      libitum. The data suggest that the GH/IGF axis is involved in the partitioning of
      nutrients between the dam and the foetus.

PMID- 8994383
TI  - Regulation of oxytocin, oestradiol and progesterone receptor concentrations in
      different uterine regions by oestradiol, progesterone and oxytocin in
      ovariectomized ewes.
AB  - The regulation of oxytocin, oestradiol and progesterone receptors in different
      uterine cell types was studied in ovariectomized ewes. Animals were pretreated
      with a progestogen sponge for 10 days followed by 2 days of high-dose oestradiol
      to simulate oestrus. They then received either low-dose oestradiol (Group E), low
      dose oestradiol plus progesterone (Group P) or low-dose oestradiol, progesterone
      and oxytocin (via osmotic minipump; Group OT). Animals (three to six per time
      point) were killed following ovariectomy (Group OVX), at oestrus (Group O) or
      following 8, 10, 12 or 14 days of E, P or OT treatment. In a final group,
      oxytocin was withdrawn on day 12 and ewes were killed on day 14 (Group OTW).
      Oxytocin receptor concentrations and localization in the endometrium and
      myometrium were measured by radioreceptor assay, in situ hybridization and
      autoradiography with the iodinated oxytocin receptor antagonist
      d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin. Oestradiol and progesterone
      receptors were localized by immunocytochemistry. Oxytocin receptors were present
      in the luminal epithelium and superficial glands of ovariectomized ewes. In Group
      O, endometrial oxytocin receptor concentrations were high (1346 +/- 379 fmol
      [3H]oxytocin bound mg protein-1) and receptors were also located in the deep
      glands and caruncular stroma in a pattern resembling that found at natural
      oestrus. Continuing low-dose oestradiol was unable to sustain high endometrial
      oxytocin receptor concentrations with values decreasing significantly to 140 +/-
      20 fmol mg protein-1 (P < 0.01), localized to the luminal epithelium and
      caruncular stroma but not the glands. Progesterone treatment initially abolished
      all oxytocin receptors with none present on days 8 or 10. They reappeared in the
      luminal epithelium only between days 12 and 14 to give an overall concentration
      of 306 +/- 50 fmol mg protein-1. Oxytocin treatment caused a small increase in
      oxytocin receptor concentration in the luminal epithelium on days 8 and 10 (20 +/
      4 in Group P and 107 +/- 35 fmol mg protein-1 in Group OT, P < 0.01) but the
      rise on day 14 was not affected (267 +/- 82 in Group OT and 411 +/- 120 fmol mg
      protein-1 in Group OTW). In contrast, oestradiol treatment was able to sustain
      myometrial oxytocin receptors (635 +/- 277 fmol mg protein-1 in Group O and 255
      +/- 36 in Group E) and there was no increase over time in Groups P, OT and OTW
      with values of 61 +/- 18, 88 +/- 53 and 114 +/- 76 fmol mg protein-1 respectively
      (combined values for days 8-14). Oestradiol receptor concentrations were high in
      all uterine regions in Group O. This pattern and concentration was maintained in
      Group E. In all progesterone-treated ewes, oestradiol receptor concentrations
      were lower in all regions at all time-points. The only time-related change
      occurred in the luminal epithelium in which oestradiol receptors were
      undetectable on day 8 but developed by day 10 of progesterone treatment.
      Progesterone receptors were present at moderate concentrations in the deep
      glands, caruncular stroma, deep stroma and myometrium in Group O. Oestradiol
      increased progesterone receptors in the luminal epithelium, superficial glands,
      deep stroma and myometrium. Progesterone caused the loss of its own receptor from
      the luminal epithelium and superficial glands and decreased its receptor
      concentration in the deep stroma and myometrium at all time-points. There was a
      time-related loss of progesterone receptors from the deep glands of progesterone
      treated ewes between days 8 and 14. These results show differences in the
      regulation of receptors between uterine regions. In particular loss of the
      negative inhibition by progesterone on the oxytocin receptor by day 14 occurred
      only in the luminal epithelium, but is unlikely to be a direct effect of
      progesterone as no progesterone receptors were present on luminal epithelial
      cells between days 8 and 14.

PMID- 8994385
TI  - The effect of epidermal growth factor on circulating levels of IGF and IGF
      binding proteins in adult Goettingen minipigs.
AB  - It has recently been demonstrated that epidermal growth factor (EGF)
      administration to neonatal rodents causes growth retardation with concomitant
      reductions in circulation levels of IGF-I. We describe the effects of systemic
      EGF administration for 4 weeks on circulating levels of IGF-I and IGF-binding
      proteins (IGFBPs) and on thyroid hormones (tri-iodothyronine, T3; thyroxine, T4)
      in sexually mature pigs. Goettingen minipigs of either sex were treated with
      placebo (n = 5) or EGF (30 micrograms/kg per day, n = 6) s.c. for 4 weeks (in
      relation to an oesophageal sclerotherapy regimen). Blood samples were taken under
      anaesthesia before and after 1, 2, 3 and 4 weeks of treatment. Circulating levels
      of IGF-I, insulin, glucose, T3 and T4 were analysed every week and IGFBPs every
      second week. IGF-I was not reduced significantly after 1 week but significantly
      reduced after 2 and 3 weeks of EGF treatment. A similar decline was observed for
      the major IGFBP, IGFBP-3, which was reduced after 2 and 4 weeks. IGFBP-1, IGFBP-2
      and IGFBP-4 increased throughout the treatment period (all significantly at week
      4). EGF treatment induced increased circulating T3 after 2, 3 and 4 weeks of EGF
      treatment. In conclusion, we report that EGF treatment for 4 weeks in Goettingen
      minipigs reduces circulating IGF-I and IGFBP-3, increases circulating IGFBP-1,
      IGFBP-2 and IGFBP-4, and induces a slight hyperthyroidism as judged from
      increased circulating levels of T3.

PMID- 8994386
TI  - Occurrence of WE-14 and chromogranin A-derived peptides in tissues of the human
      and bovine gastro-entero-pancreatic system and in human neuroendocrine neoplasia.
AB  - Antisera were generated to the synthetic peptides SREWEDS and KELTAE which
      correspond to residues 315-321 and 332-337 of human chromogranin A (CgA)
      respectively. KELTAE represents the C-terminal hexapeptide of WE-14, and SREWEDS
      (residue 316 human CgA Lys/Arg substitution) represents the C-terminal
      heptapeptide of the Intervening Peptide, located between pancreastatin and WE-14.
      The antisera were employed to study the occurrence of WE-14 and CgA-derived
      peptides in human and bovine gastro-entero-pancreatic (GEP) tissues and in a
      range of human GEP neuroendocrine tumours. Immunocytochemical analyses of normal
      human and bovine tissues demonstrated that each antiserum immunostained endocrine
      cells throughout the GEP tract, Variable intensities of immunostaining were
      detected in neoplastic tissues. Quantitatively, the highest levels of SREWEDS and
      KELTAE immunoreactivity were detected in pancreatic extracts, with lower levels
      in gastrointestinal tissues. Elevated levels of each immunoreactant were detected
      in neoplastic tissues. Chromatographic analysis resolved several SREWEDS-related
      peptides and a major KELTAE-related peptide that co-eluted with synthetic human
      WE-14. The present study has demonstrated that CgA is processed to generate
      distinct peptide products in normal and neoplastic tissues of the GEP system. A
      single molecular species co-eluting with synthetic human WE-14 was predominant
      and consistently detected in all the tissues studied.

PMID- 8994387
TI  - Luminal peptide YY-releasing factors in the isolated vascularly perfused rat
      colon.
AB  - Peptide YY (PYY) is produced in endocrine L cells primarily localized in the
      distal bowel. These open-type L cells make contact with the intestinal chyme
      which may thus affect their secretory activity. The aim of the present study was
      to examine a large variety of luminal compounds found in colonic contents for
      their potential as PYY-releasing factors, using the isolated vascularly perfused
      rat colon. The release of PYY into the portal effluent was measured by a specific
      RIA. Luminal administration of 5 mM glucose or 0.5% (w/v) starch for 30 min did
      not induce significant release of PYY. Oleic acid (10 and 100 mM) also did not
      significantly increase PYY secretion. A pharmacological concentration of glucose
      (250 mM) and a mixture of amino acids (total concentration 250 mM) both induced
      PYY secretion (200% of basal). Pectin, a poly-galacturonic acid, evoked dose
      dependent secretion of PYY-like immunoreactivity over the range 0.1-0.5% (w/v).
      The maximal response was observed after infusion of 0.5% pectin which induced a
      prompt and sustained release of PYY (300% of basal). Galacturonic acid itself
      (5%) produced marked PYY secretion. Gum arabic (0.5%) induced a gradual increase
      in portal PYY concentration (maximal response 250% of the basal value) whereas
      cellulose (0.5%) did not elicit PYY secretion. Luminal n-butyrate over the range
      0.5-5 mM produced a dose-dependent release of PYY (maximal response 300% of the
      basal value with 5 mM n-butyrate). Increasing the concentration of n-butyrate to
      100 mM provoked a gradual decrease in PYY secretion. Propionate was a less potent
      stimulant than n-butyrate, and acetate did not increase PYY secretion above the
      basal value. At a concentration of 2 or 20 mM, taurocholate, cholate and
      deoxycholate brought about PYY secretion while hyodeoxycholate was without
      effect. In conclusion, glucose and amino acids may mediate PYY release but only
      when they are present at high supraphysiological concentrations in the colon
      while oleic acid does not produce any PYY secretion. Physiological concentrations
      of fibers (pectin, gum arabic), short-chain fatty acids (n-butyrate, propionate)
      and bile salts (taurocholate, cholate, deoxycholate) are all potent stimulants of
      PYY release. Whether the release of PYY by luminal factors is coupled to water
      and electrolyte transfer via a local/paracrine pathway remains an open question
      which requires additional work with the isolated vascularly perfused colon
      preparation.

PMID- 8994388
TI  - Thyroxine effect on intestinal Cl-/HCO3- exchange in hypo- and hyperthyroid rats.
AB  - Changes in transepithelial water and electrolyte transport as causative or
      contributing factors of the diarrhoea and constipation found associated with
      changes in thyroid physiology were studied. Albino Wistar rats were
      pharmacologically made either hypothyroid or hyperthyroid. After sacrifice, the
      small intestine was mounted in Ussing chambers in order to measure in vitro ion
      net fluxes under short-circuit conditions. Hypothyroid animals showed an increase
      in intestinal transit time, Cl- absorption (mainly due to an increment in its
      mucosal to serosal component) and residual ion flux (which is believed to
      represent HCO3- secretion) when compared with euthyroid animals. The hyperthyroid
      animals showed a decrease in Cl- mucosal to serosal transport. Furthermore, a
      significant correlation was found between serum L-thyroxine (T4) levels and both
      net Cl- transport (r = -0.74, P < 0.00001) and residual ion flux (r = -0.55, P <
      0.005). These results indicate that the effect of T4 is firstly to inhibit Cl
      /HCO3- anion exchange thereby influencing transepithelial flux transport and
      secondly to affect intestinal motility. Such inhibition was not found when T4 was
      acutely added to rat ileum, suggesting that the effect on electrolyte transport
      probably requires protein synthesis. In conclusion, the phenomenon observed in
      vitro could explain the clinical manifestations of constipation and diarrhoea in
      hypo- and hyper-thyroidism respectively.

PMID- 8994389
TI  - Dopaminergic regulation of adrenocorticotrophic hormone, alpha-melanocyte
      stimulating hormone and cortisol secretion in the ovine fetus.
AB  - During ovine fetal development there is a progressive maturation of the
      hypothalamo-pituitary-adrenal axis which culminates in the onset of birth. The
      role and regulation of the intermediate lobe of the fetal pituitary gland in
      relation to this maturational process remains controversial. To test the
      hypothesis that the pars intermedia of the ovine fetal pituitary is under tonic
      inhibitory dopaminergic control we treated fetal sheep at day 131 of gestation
      with a 3-day intravenous infusion of one of the following: the dopamine
      antagonist sulpiride (0.3 mg/ 0.5 ml/h; n = 12), the dopamine agonist
      bromocriptine (0.03 mg/0.5 ml/h; n = 7) or vehicle (0.1 M tartaric acid in
      saline; n = 8) alone. Fetal plasma concentrations of alpha-MSH were significantly
      (P < 0.01) increased by treatment with sulpiride and decreased (P < 0.05) by
      bromocriptine. The increase in alpha-MSH after sulpiride was characterised by an
      increase in the amplitude of alpha-MSH pulses whereas bromocriptine virtually
      abolished all pulses of alpha-MSH. Immunoreactive ACTH (IR-ACTH) concentrations
      were significantly (P < 0.05) elevated after sulpiride but were unaffected by
      bromocriptine. There were no changes in the pulsatile characteristics of IR-ACTH
      secretion. Cortisol concentrations were unchanged by either treatment. We
      conclude that fetal alpha-MSH and IR-ACTH are secreted in a pulsatile fashion and
      are tonically inhibited by dopaminergic pathways. The lack of an effect of
      endogenously raised alpha-MSH on plasma cortisol concentrations provides evidence
      that this POMC-derived peptide is not responsible for the regulation of cortisol
      biosynthesis and/or secretion.

PMID- 8994390
TI  - Cytokine modulation of inhibin secretion in cultured rat granulosa cells.
AB  - In the present study, we examined the effects of tumour necrosis factor alpha
      (TNF alpha) and interleukin-1 beta (IL-1 beta) on inhibin secretion by cultured
      rat granulosa cells using immunoblotting and two-site enzyme immunoassay for
      inhibin A (alpha-beta A dimer). FSH stimulated the secretion of the inhibin alpha
      beta A dimer (32 kDa) by the cells in a dose-dependent manner. In addition to the
      predominant 32 kDa inhibin alpha-beta A dimer staining, staining of minor
      immunoreactive bands was also enhanced by FSH. TNF alpha alone did not have any
      effect on inhibin secretion. Immunoblot analyses using an antiserum against alpha
      subunit and an antiserum against beta A-subunit revealed a dose-dependent
      inhibition by TNF alpha of FSH-stimulated secretion of inhibin by rat granulosa
      cells. Similarly, TNF alpha inhibited in a dose-dependent manner FSH-stimulated
      inhibin secretion when measured using a two-site enzyme immunoassay. IL-1 beta
      alone did not exert any effect on inhibin secretion but it inhibited FSH
      stimulated inhibin release in a dose-dependent manner (using both immunoblotting
      and a two-site assay for inhibin A). The present observations suggest that TNF
      alpha and IL-1 beta inhibit gonadotrophin-stimulated inhibin production by
      cultured rat granulosa cells.

PMID- 8994391
TI  - Hepatocyte growth factor/scatter factor and its receptor c-met: localisation and
      expression in the human placenta throughout pregnancy.
AB  - Hepatocyte growth factor (HGF), also known as scatter factor, acts via the c-met
      receptor resulting in pronounced effects on certain epithelial cells. We
      hypothesised that HGF would be important in placental development where the
      trophoblast represents a specialised barrier of epithelial origin. In this paper
      we examine the expression and production of HGF and its receptor in the human
      placenta throughout pregnancy. In addition, RT-PCR was undertaken on human
      embryos to ascertain whether pre-implantation embryonic or trophoblast cells were
      under the influence of this growth factor. In samples from the first trimester of
      pregnancy in situ hybridisation with a c-met antisense probe detected message
      expression in villous cytotrophoblast and in decidual glands but not in
      extravillous trophoblast. Some c-met expression was detected in cytotrophoblast
      from the second trimester placentae; this declined to negligible levels by term.
      Staining with an anti c-met antibody largely confirmed these findings but found
      relatively strong staining of cytotrophoblast at term. HGF was confined to the
      villous core throughout pregnancy when examined by both in situ hybridisation and
      immunohistochemistry. Trophoblast was consistently negative for HGF. Pre
      implantation embryos examined by RT-PCR were negative for both c-met and HGF
      mRNA. These results indicate that the HGF may exert an important influence on
      cytotrophoblast throughout the process of placental formation and growth.

PMID- 8994392
TI  - Effect of lactation on insulin signal transduction in sheep adipose tissue and
      skeletal muscle.
AB  - The molecular basis of the insulin resistance of adipocytes and skeletal muscle
      during lactation has been investigated in sheep. The number of insulin receptors
      per adipocyte or per unit membrane protein for skeletal muscle is unchanged by
      lactation. The ability of insulin to stimulate autophosphorylation of its beta
      subunit was enhanced in adipocytes but not in skeletal muscle during lactation.
      This increased autophosphorylation was due, at least in part, to enhanced
      tyrosine phosphorylation and was found when both solubilised, immunoprecipitated
      insulin receptors and intact adipocytes were incubated with insulin. The ability
      of the insulin receptor kinase to phosphorylate other proteins did not appear to
      be altered by lactation; this was shown with lectin-purified insulin receptors
      using the artificial substrate, polyglutamyl tyrosine, and in intact adipocytes.
      Lactation had no effect on the ability of insulin to activate two key downstream
      kinases, mitogen-activated protein kinase and phosphatidyl inositol-3-kinase in
      adipocytes. The study thus shows that the insulin resistance of lactation in
      sheep is due to changes downstream of the receptor in both adipocytes and
      skeletal muscle.

PMID- 8994393
TI  - Characterization of the ovine LH beta-subunit gene: the promoter is regulated by
      GnRH and gonadal steroids in transgenic mice.
AB  - We have previously demonstrated that 1.9 kb of ovine LH beta promoter fused to
      bacterial chloramphenicol transferase (CAT) coding sequence is sufficient to
      target expression of the transgene specifically to the gonadotroph cells of the
      anterior pituitary in mice with no expression being observed in other tissues.
      However, it is not known if this region of the ovine LH beta promoter contains
      the necessary elements that confer transcriptional regulation by gonadal steroids
      and GnRH. Following gonadectomy, both endogenous pituitary LH and CAT activity
      significantly (P > 0.001) increased as did plasma LH. This post-gonadectomy
      increase in CAT, pituitary and plasma LH could be suppressed in females by
      treatment with oestradiol alone or oestradiol and progesterone, with an
      additional significant (P < 0.05) reduction in CAT activity being observed in one
      line following the combined steroid treatment. In castrated males, testosterone
      suppressed CAT activity in one line. Treatment of transgenic ovariectomized
      females with oestradiol alone significantly suppressed plasma LH (P < 0.01) with
      no change in pituitary LH content. There was no difference in pituitary LH
      between oestradiol-treated ovariectomized transgenic and non-transgenic females.
      Treatment of intact females from both lines with either GnRH antiserum or agonist
      demonstrated a decrease in pituitary CAT activity whereas similar treatment in
      intact males had no effect. While endogenous pituitary LH concentrations were
      variable, plasma LH was lower in all treated animals irrespective of line, sex or
      expression of the transgene. In conclusion, these results indicate that (1) the
      presence of CAT protein is not toxic and does not compromise either endogenous LH
      synthesis, storage and secretion and (2) the ovine LH beta-CAT gene is regulated
      in a similar but more variable manner to the endogenous LH beta gene. This may
      relate to the use of CAT as a reporter where its release is not necessarily
      related to that of the endogenous hormone whose synthesis, storage and release
      may differ.

PMID- 8994394
TI  - Sclerotome-related helix-loop-helix type transcription factor (scleraxis) mRNA is
      expressed in osteoblasts and its level is enhanced by type-beta transforming
      growth factor.
AB  - Scleraxis is a recently identified transcription factor with a basic helix-loop
      helix motif, which is expressed in sclerotome during embryonic development. We
      have examined the expression of scleraxis mRNA in rat osteoblastic cells and
      found that the scleraxis gene was expressed as a 1.2 kb mRNA species in
      osteoblastic osteosarcoma ROS17/2.8 cells. The scleraxis mRNA expression was
      enhanced by type-beta transforming growth factor (TGF beta) treatment. The TGF
      beta effect was observed in a dose-dependent manner starting at 0.2 ng/ml and
      saturating at 2 ng/ml. The effect was time-dependent and was first observed
      within 12 h and peaked at 24 h. The TGF beta effect was blocked by cycloheximide,
      while no effect on scleraxis mRNA stability was observed. TGF beta treatment
      enhanced scleraxis-E box (Scx-E) binding activity in the nuclear extracts of
      ROS17/2.8 cells. Furthermore, TGF beta enhanced transcriptional activity of the
      CAT constructs which contain the Scx-E box sequence. TGF beta treatment also
      enhanced scleraxis gene expression in osteoblast-enriched cells derived from
      primary rat calvaria. These findings indicated for the first time that the novel
      helix-loop-helix type transcription factor (scleraxis) mRNA is expressed in
      osteoblasts and its expression is regulated by TGF beta.

PMID- 8994395
TI  - Stimulatory effects of taurine on insulin secretion by fetal rat islets cultured
      in vitro.
AB  - Islets of rat fetuses born to mothers fed a low protein diet (LP) have a
      depressed insulin secretion in vitro in response to secretagogues. These fetuses
      have lower plasma levels of taurine than controls. The aim of this study was to
      analyze the effect of taurine on fetal islets insulin secretion. After 5 days of
      culture in serum containing standard RPMI medium, islets were cultured for 2 days
      in serum-free DME/F12 medium with 8.2 or 16.7 mM glucose alone or with taurine at
      0.3 or 3 mM. They were then incubated for 120 min in Krebs Ringer solution with
      glucose alone (5.6 or 16.7 mM) or glucose (5.6 mM) added to leucine or arginine
      (both at 10 mM). In both concentrations of glucose, taurine increased the
      fractional insulin release by islets stimulated with secretagogues tested during
      the incubation. The effect did not seem to be mediated by changes in cAMP
      content. In a second set of experiments, islets cultured in RPMI medium for 7
      days were incubated in the presence of Krebs Ringer solution with leucine (10 mM)
      or with sulfur amino acids (taurine at 10 mM, methionine or cysteine at 5 mM) for
      120 min. Taurine and methionine stimulated insulin release at the same magnitude
      as leucine, whereas cysteine had no effect. In conclusion, taurine enhances
      insulin secretion by fetal islets, at least in vitro. Low taurine levels in
      fetuses from LP mothers might be implicated in their depressed insulin secretion.

PMID- 8994396
TI  - Diet-induced obesity and pancreatic islet blood flow in the rat: a preferential
      increase in islet blood perfusion persists after withdrawal of the diet and
      normalization of body weight.
AB  - The aim of the present study was to evaluate the effects of diet-induced obesity
      on pancreatic islet blood perfusion in normal Wistar rats. Furthermore, we
      investigated to what extent any obesity-associated changes in islet blood flow
      could be reversed after reversion to a normal diet with normalization of body
      weight. Young adult female Wistar rats were offered a palatable mixed high
      caloric diet (cafeteria diet) in addition to standard pelleted chow. Age-matched
      control rats received standard pelleted chow only. After 4 weeks the diet-treated
      rats had a body weight of approximately 15% more than that of the controls. All
      diet-treated rats had decreased glucose tolerance and increased serum insulin
      concentrations, but basal blood glucose concentrations were similar in
      anesthetized diet-treated and control rats. Whole pancreatic and islet blood flow
      rates were measured with a microsphere technique. The islet blood flow as well as
      fractional islet blood flow were increased (P < 0.01) in rats fed the cafeteria
      diet, while blood perfusion of the whole pancreas was similar to that of the
      control rats. In a second experiment, rats received the cafeteria diet for 4
      weeks and were then fed standard pelleted food alone for another 3 weeks, while
      controls received standard diet for 7 weeks. After this period total body weight,
      retroperitoneal fat pad weight and glucose tolerance were similar to those of the
      controls. Whole pancreatic blood flow was unchanged as compared with that of
      control rats. However, both islet blood flow (P < 0.01) and fractional blood flow
      (P < 0.01) were increased. We conclude that diet-induced obesity in rats is
      associated with decreased glucose tolerance, hyperinsulinemia and a specific
      increase in absolute and fractional islet blood perfusion. This increase persists
      for at least 3 weeks after the diet is withdrawn despite normalization of body
      weight and glucose tolerance.

PMID- 8994397
TI  - Application of meta-analysis in reviewing occupational cohort studies.
AB  - Meta-analysis has been used increasingly in reviewing and summarising
      epidemiological studies. Reviews incorporating meta-analyses have appeared in
      medical journals in increasing numbers. Although there are several methodology
      papers on meta-analysis, most of these papers have been written primarily for
      discussion among epidemiologists. The present paper considers some of the basic
      methodological issues, the more practical aspects of meta-analysis, and targets
      an audience of mainly non-epidemiologists. Thus, the main objective of this paper
      is to provide some basic guidelines for non-epidemiologists to evaluate meta
      analysis in occupational cohort studies. In this methodology paper, the
      limitations and problems of traditional qualitative reviews are pointed out. Some
      of these problems can be dealt with by quantitative meta-analysis. The potential
      limitations and benefits of quantitative meta-analysis are discussed. Rather than
      replacing traditional qualitative review, quantitative meta-analysis should be
      made part of the overall assessment. The term "meta-review" is proposed to
      emphasise the importance of both qualitative and quantitative components in a
      comprehensive review process. The basic steps in a meta-review are outlined, with
      a discussion on how to recognise and avoid some of the problems which are likely
      to occur at each step. A meta-review is useful in selecting studies, and in
      organising, presenting, and summarising results from individual studies. A meta
      review can also be used to detect heterogeneity among studies. Major benefits of
      conducting a meta-analysis (the quantitative component in a meta-review) include
      the increase in statistical power and the estimate of a properly weighted summary
      risk estimate.

PMID- 8994399
TI  - Relation of spirometric function to radiographic interstitial fibrosis in two
      large workforces exposed to asbestos: an evaluation of the ILO profusion score.
AB  - OBJECTIVES: To analyse quantitatively the relations of spirometric lung function
      (forced vital capacity (FVC)) to radiographic interstitial pulmonary fibrosis
      (assessed by the International Labour Organisation (ILO) profusion score of small
      irregular opacities) in two large workforces exposed to different intensities of
      asbestos. These analyses consider the question whether a similar profusion score
      n differently exposed workers is associated with a similar effect on lung
      function. METHODS: Surveys of two workforces, insulators (n = 2611) and sheet
      metal workers (n = 1245), by the same investigators allowed comparison of the
      effects of the two levels of exposure to asbestos. The two groups were of similar
      age and had similar percentages of non-smokers and smokers. All radiographs were
      read by the same expert reader. RESULTS: Consistent with their less continuous
      and less intense exposure to asbestos, metal workers had: (a) far less frequent
      radiographic asbestosis (profusion score > or = 1/0, 17.5% v 59.6% for
      insulators): (b) less severe radiographic asbestosis (only 1.1% had scores > or =
      2/1 v 13.3% of insulators); (c) a similar slope to that seen in insulators for
      the relation between FVC and profusion score when pleural thickening was absent;
      (d) less frequent pleural fibrosis (36% v 75%); and (e) less frequent restrictive
      impairment (23% v 33%). In both insulators and metal workers, lung function was
      below normal even when lung fields were normal, FVG fell with increasing
      profusion, it was lower in smokers and in those with pleural thickening at
      comparable profusion scores, and these was no difference in FVC between scores
      0/1 and 1/0. CONCLUSION: The decrease in FVC with increasing profusion score in
      both workforces as well as the similar slopes for the relation between FVG and
      profusion score and the similar FVG at similar scores in the absence of pleural
      thickening confirm the ILO profusion score as an acceptable assessment of
      pulmonary fibrosis.

PMID- 8994398
TI  - Retention of asbestos fibres in lungs of workers with asbestosis, asbestosis and
      lung cancer, and mesothelioma in Asbestos township.
AB  - OBJECTIVE: To conduct a mineralogical study on the particles retained in the
      necropsied lungs of a homogenous group of asbestos miners and millers from
      Asbestos township (and a local reference population) and to consider the
      hypothesis that there is a difference in size between fibres retained in the
      lungs of patients with asbestosis with and without lung cancer. METHODS: Samples
      of lung tissue were obtained from 38 patients with asbestosis without lung
      cancer, 25 with asbestosis and lung cancer, and 12 with mesothelioma, from
      necropsied Quebec chrysotile miners and millers from Asbestos township. Fibre
      concentrations in the lungs of these patients were compared with those in tissue
      from necropsies carried out on a local reference population: men who had died of
      either accidental death or acute myocardial infarction between 1990 and 1992. 23
      were born before 1940 and 26 after 1940. RESULTS: Geometric mean (GM)
      concentrations were higher in cases than in the controls for chrysotile fibres 5
      to 10 microns long in patients with asbestosis with or without lung cancer; for
      tremolite fibres 5 to 10 microns long in all patients; for crocidolite, talc, or
      anthophyllite fibres 5 to 10 microns long in patients with mesothelioma; for
      chrysotile and tremolite fibres > or = 10 microns long in patients with
      asbestosis; and crocidolite, talc, or anthophyllite fibres > or = 10 microns long
      in patients with mesothelioma. However, median concentrations of each type of
      fibre in the lungs did not show any significant differences between the three
      disease groups. Average length to diameter ratios of the fibres were calculated
      to be larger in patients with asbestosis and lung cancer than in those without
      lung cancer for crocidolite fibres > or = 10 microns long, for chrysotile,
      amosite, and tremolite fibres 5 to 10 microns long, and for chrysotile and
      crocidolite fibres < 5 microns long. However, there was no statistical difference
      in the median length to diameter ratios for any type of fibres across the disease
      groups when they were calculated in each patient. Cumulative smoking index (pack
      years) was higher in the group with asbestosis and lung cancer but was not
      statistically different from the two other disease groups. CONCLUSION: Lung
      cancers occurred in workers with asbestosis from Asbestos township who had an
      equal concentration of retained fibres but a tendency to a higher length to
      diameter ratio of amphiboles. These workers had a 29% higher average cumulative
      smoking index.

PMID- 8994400
TI  - Induction of mesothelioma after intrapleural inoculation of F344 rats with
      silicon carbide whiskers or continuous ceramic filaments.
AB  - OBJECTIVE: To find whether continuous ceramic filaments (CCFs) and silicon
      carbide whiskers (SiCWs), which are used in many industries as reinforcing
      materials in advanced ceramic composites, are carcinogenic in the intrapleural
      inoculation assay. METHODS: Samples of SiCWs, CCF, International Union Against
      Cancer crocidolite, or saline were injected into the pleural cavities of female
      F344/N rats to find whether the samples of SiCW and CCF had the potential to
      induce mesotheliomas after the direct application of the materials to the surface
      of the pleural mesothelium. RESULTS: Rats injected with two of the three
      individual samples of SiCW or the crocidolite had significantly reduced life
      spans compared with the rats treated with saline, CCFs, or the third SiCW sample.
      Rats treated with either of the two SiCW samples or crocidolite developed
      mesotheliomas. By contrast, rats treated with saline or CCF did not. The two SiCW
      samples that induced shortened life spans also induced a higher rate of
      mesothelioma (87%-90%), than the crocidolite (57%) and the third SiCW sample
      (23%). CONCLUSION: SiCWs but not CCFs could induce mesotheliomas after
      intrapleural injection in rats. The difference in biological activity between the
      SiCW samples could not be explained on the basis of their physical dimensions or
      biological activity toward cultured cells. Results from this study indicated that
      SiCWs should be handled with care as they might be carcinogenic if inhaled.
      However, there is controversy as to whether results of intrapleural injection
      assays are sufficient to determine a fibre's carcinogenic activity. The results
      also showed that a collection of fibrous materials such as SiCWs could have
      considerably different biological activities despite similar physical dimensions.

PMID- 8994401
TI  - Adverse health effects of PM10 particles: involvement of iron in generation of
      hydroxyl radical.
AB  - OBJECTIVES: Environmental particles < 10 microns average aerodynamic diameter
      (PM10) are associated with mortality, exacerbation of airways diseases, and
      decrement in lung function. It is hypothesised that PM10 particles, along with
      other pathogenic particles, generate free radicals at their surface in reactions
      involving iron, and that this is a factor in the pathogenicity of PM10 particles.
      Identification of free radical activity in PM10 and examination of the content
      and role of iron in this process was undertaken. METHODS: Free radical activity
      was detected with a supercoiled plasmid, phi X174 RF1 DNA, and measured as
      scission of the supercoiled DNA (mediated by free radicals) by scanning laser
      densitometry. The role of the hydroxyl radical was confirmed by the use of the
      specific scavenger mannitol, and the role of iron investigated with the iron
      chelator desferrioxamine-B (DSF-B). Iron released from PM10 particles at pH 7.2
      and pH 4.6 (to mimic conditions on the lung surface and in macrophage
      phagolysosomes, respectively) was assessed spectrophotometrically with the Fe++
      chelator ferrozine and the Fe+ + + chelator DSF-B. RESULTS: PM10 particles showed
      significant free radical activity by their ability to degrade supercoiled DNA. A
      substantial part of this activity was due to the generation of hydroxyl radicals,
      as shown by partial protection with mannitol. Similarly, DSF-B also conferred
      protection against the damage caused to plasmid DNA indicating the role of iron
      in generation of hydroxyl radicals. Negligible Fe++ was released at either pH 7.2
      or pH 4.6 by contrast with Fe+ + +, which was released in substantial quantities
      at both pHs, although twice as much was released at pH 4.6. CONCLUSIONS: PM10
      particles generate the hydroxyl radical, a highly deleterious free radical, in
      aqueous solution. This occurs by an iron dependent process and hydroxyl radicals
      could play a part in the pathogenicity of PM10 particles. Iron release was
      greatest at the pH of the lysosome (pH 4.6) indicating that iron may be mobilised
      inside macrophages after phagocytosis, leading to oxidative stress in the
      macrophages.

PMID- 8994402
TI  - Incidence of childhood leukaemia and non-Hodgkin's lymphoma in the vicinity of
      nuclear sites in Scotland, 1968-93.
AB  - OBJECTIVES: The primary aims were to investigate the incidence of leukaemia and
      non-Hodgkin's lymphoma in children resident near seven nuclear sites in Scotland
      and to determine whether there was any evidence of a gradient in risk with
      distance of residence from a nuclear site. A secondary aim was to assess the
      power of statistical tests for increased risk of disease near a point source when
      applied in the context of census data for Scotland. METHODS: The study data set
      comprised 1287 cases of leukaemia and non-Hodgkin's lymphoma diagnosed in
      children aged under 15 years in the period 1968-93, validated for accuracy and
      completeness. A study zone around each nuclear site was constructed from
      enumeration districts within 25 km. Expected numbers were calculated, adjusting
      for sex, age, and indices of deprivation and urban-rural residence. Six
      statistical tests were evaluated. Stone's maximum likelihood ratio (unconditional
      application) was applied as the main test for general increased incidence across
      a study zone. The linear risk score based on enumeration districts (conditional
      application) was used as a secondary test for declining risk with distance from
      each site. RESULTS: More cases were observed (O) than expected (E) in the study
      zones around Rosyth naval base (O/E 1.02), Chapelcross electricity generating
      station (O/E 1.08), and Dounreay reprocessing plant (O/E 1.99). The maximum
      likelihood ratio test reached significance only for Dounreay (P = 0.030). The
      linear risk score test did not indicate a trend in risk with distance from any of
      the seven sites, including Dounreay. CONCLUSIONS: There was no evidence of a
      generally increased risk of childhood leukaemia and non-Hodgkin's lymphoma around
      nuclear sites in Scotland, nor any evidence of a trend of decreasing risk with
      distance from any of the sites. There was a significant excess risk in the zone
      around Dounreay, which was only partially accounted for by the sociodemographic
      characteristics of the area. The statistical power of tests for localised
      increased risk of disease around a point source should be assessed in each new
      setting in which they are applied.

PMID- 8994403
TI  - Concentration of blood lead and ethnicity in the United Kingdom.
AB  - The relation between concentration of blood lead and ethnic background in 779
      children was examined with the analytical results from the trace element service
      at the Medical Toxicology Unit (MTU), Guy's and St Thomas's Hospital Trust for
      the period 1980-94. The ethnic identity was determined with the first and the
      second names of the investigated subjects. Of the patients of European origin
      (European) studied 72.8% v only 50.6% of the children with origins in the Indian
      subcontinent (Asian) had a concentration of blood lead < 100 micrograms/l. The
      percentage of subgroups with concentrations above the upper acceptable limit of
      200 micrograms/l was significantly higher in Asian subjects (European 5% v Asian
      26.5%), with the most pronounced difference in those with concentrations of blood
      lead of 500 micrograms/l (European 0.8% v Asian 10.5%). This study shows that a
      correlation exists between Asian ethnic background and concentration of blood
      lead in children. Factors such as cultural habits-for example, use of traditional
      remedies, cosmetics, diet- and socioeconomic status, may have contributed to this
      results.

PMID- 8994404
TI  - Morbidity study of extruder personnel with potential exposure to brominated
      dioxins and furans. II. Results of clinical laboratory studies.
AB  - OBJECTIVE: To test whether dioxins affect liver and thyroid function, lipid
      metabolism and glucose or immunological variables, in workers exposed to
      brominated dioxins and furans. METHODS: 34 male production employees (29 were
      extruder operators) and eight technical support personnel were studied, all of
      whom were potentially exposed to polybrominated dibenzo-p-dioxins (PBDDs) and
      furans (PBDFs) during production of resins containing polybrominated diphenyl
      ethers (PBDEs). Controls were from a similar resin producing plant that did not
      use PBDEs. Blood samples were analysed for tetra, penta, and hexabrominated
      congeners, but 2,3,7,8-TBDD was the only exposure measure used in the regression
      analyses. Seven liver function indicators, five measures of blood lipids and
      glucose, four haematology and blood coagulation measures, and three measures of
      thyroid function were examined. RESULTS: None of the variables was statistically
      related to concentration of 2,3,7,8-TBDD in the regression analyses. Cigarette
      smoking was related to several outcomes at the 0.05 level: aspartate
      aminotransferase, alanine aminotransferase, glutamate dehydrogenase (GLDH),
      erythrocyte sedimentation rate, and white blood cell count. Body mass index was
      also related to alanine aminotransferase, gamma-glutamyltranspeptidase,
      cholinesterase, GLDH, cholesterol, triglycerides, high density lipoprotein, low
      density lipoprotein, and glucose concentrations. No definitive associations
      between liver, blood lipid, thyroid, or immunological variables and exposure to
      brominated dioxins or blood lipid concentration of 2,3,7,8-TBDD were found.
      CONCLUSIONS: The study population was small and hence the findings must be
      interpreted with caution. Nevertheless, these results provide a base for
      interpreting the results of clinical studies in similarly exposed populations.

PMID- 8994405
TI  - Small LDL, atherogenic dyslipidemia, and the metabolic syndrome.

PMID- 8994406
TI  - Atherogenic lipids, vascular dysfunction, and clinical signs of ischemic heart
      disease.
AB  - LDL is oxidized in vascular endothelial cells to a highly injurious product that
      results in characteristic cell dysfunction(s) in large arteries and resistance
      vessels. The characteristic dysfunctions (ie, loss of dilation, constriction,
      thrombosis, and inflammation) operate before and throughout the development of
      atherosclerosis and particularly during plaque rupture. Although oxidized LDL
      appears to induce these cell/vessel wall dysfunctions in a time- and
      concentration-dependent manner, Tamai and colleagues have shown that this
      interaction can be dynamic in that a reduction in lipids restores endothelium
      dependent vasomotor function almost immediately. The same intervention (ie, lipid
      lowering) also appears to stabilize atheroma in the long term, improves
      endothelium-dependent vasomotion over months, and results in a reduction in
      clinical signs of risk in coronary heart disease (ie, ischemia and the need for
      revascularization). The above leads us to some important but unanswered
      questions. Can we rely on clinical measures of arterial vasomotor dysfunction to
      represent the other important cell dysfunctions (eg, inflammation, abnormal
      growth) while monitoring the response to therapeutic interventions? How can we
      effectively inhibit oxidation of LDL in the arterial wall, and is this useful in
      reversing the many cell dysfunctions and clinical sequelae of coronary
      atherosclerosis? What is the time course for restoration of endothelial
      dysfunction in the atherosclerotic epicardial coronary arteries in patients with
      effective lipid-lowering therapy? The intracellular responses to oxidized LDL are
      so numerous (loss of vasodilation, loss of anticoagulant mechanisms, abnormal
      inflammation, and growth) that targeting therapies to specific pathways may prove
      difficult. Parallel efforts in basic physiological and clinical research have
      resulted in remarkable progress that has improved outcomes in patients with
      coronary heart disease. We expect that many of the characteristic cell/vessel
      wall dysfunctions that result from adverse interactions with risk factors are
      dynamic and can be manipulated in a relatively short time frame. Treatment of
      atherogenic lipids with other risk factors must be further refined and may well
      become the cornerstone for effective management of angina, unstable syndromes,
      and ischemia in addition to the control of important outcomes such as myocardial
      infarction and coronary death.

PMID- 8994407
TI  - Dobutamine stress echocardiography. Stressing the indications for preoperative
      testing.
AB  - Poldermans et al have added important data to the body of literature supporting
      the use of dobutamine stress echocardiography to define long-term cardiac risk
      for patients undergoing major vascular surgery. In the application of this or any
      other noninvasive study, it will remain important to select the appropriate
      population for testing. In the case of noninvasive testing before vascular
      surgery, the population should consist of patients at intermediate risk of an
      adverse cardiac event rather than the whole population with known or suspected
      coronary artery disease. If this is done, testing can be restricted to a group
      for whom results will affect clinical decision making. Clinical assessment should
      remain the first method of patient screening. Among patients identified by
      clinical markers as at intermediate risk for a perioperative or late cardiac
      event, noninvasive testing such as dobutamine stress echocardiography may be used
      to better stratify risk and to help guide perioperative and subsequent cardiac
      management.

PMID- 8994408
TI  - Simply read: erythrocytes modulate platelet function. Should we rethink the way
      we give aspirin?

PMID- 8994409
TI  - Modulation of myocardial oxygen consumption through ACE inhibitors. NO effect?

PMID- 8994410
TI  - Dilated cardiomyopathy associated with deficiency of the cytoskeletal protein
      metavinculin.
AB  - BACKGROUND: The cytoskeleton plays an important role in maintaining cell
      structure and integrity. Defects in cytoskeletal proteins can cripple cell
      strength and may cause cardiomyopathy. We analyzed heart tissues from subjects
      with dilated cardiomyopathy for abnormalities in the cardiac cytoskeleton.
      Metavinculin, a cardiac isoform of the cytoskeletal protein vinculin, connects
      actin microfilaments to the intercalated disk and membrane costameres of the
      heart. METHODS AND RESULTS: Metavinculin and vinculin transcripts and protein
      were analyzed by polymerase chain reaction (PCR) and Western blotting. Thirty
      three human heart specimens were studied, including 5 normal controls, 4 subjects
      with ischemic cardiomyopathy, 1 with X-linked cardiomyopathy, and 23 with
      idiopathic dilated cardiomyopathy (IDC). PCR of cardiac cDNA detected absence of
      the metavinculin transcript in cardiac tissue from a subject with IDC. PCR of
      genomic DNA showed that the metavinculin exon was present but not utilized in the
      cardiac transcript. Western blot analysis demonstrated absence of metavinculin
      protein in the heart from this subject. Immunostaining of cardiac vinculin in
      this heart showed disorganized intercalated disk structures. Metavinculin
      deficiency was associated with normal cardiac expression of the cytoskeletal
      proteins vinculin, alpha-actinin, and dystrophin. Normal metavinculin expression
      in the other heart specimens suggests that the defect is specific in the IDC
      subject identified. CONCLUSIONS: These results demonstrate an association between
      metavinculin deficiency and dilated cardiomyopathy due to a defect in alternative
      mRNA splicing.

PMID- 8994411
TI  - Methylenetetrahydrofolate reductase gene and coronary artery disease.
AB  - BACKGROUND: Hypermocysteinemia has been substantiated as a risk factor for
      occlusive vascular disease. A common mutation (nucleotide 677 C-->T) has been
      described recently in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene,
      which results in a valine for alanine substitution, a thermolabile enzyme, and a
      tendency to elevate plasma homocysteine levels and which has been proposed to
      contribute importantly to coronary artery disease. METHODS AND RESULTS: To study
      the potential influence of the mutation on ischemic heart disease, we screened
      555 whites with angiographically documented coronary artery disease and 143
      unrelated control subjects without a history of angina or myocardial infarction
      randomly selected from the community. The patients were in two groups: group 1
      comprised 358 prospectively recruited individuals younger than 50 years, and
      group 2, 197 patients investigated prospectively for restenosis 6 months after
      coronary angioplasty. The frequency of homozygosity for the mutation was 10.5% in
      control subjects, 10.6% in group 1, and 9.1% in group 2 patients. There was no
      relationship between MTHFR genotype and number of coronary vessels with > 50%
      diameter obstruction, prior myocardial infarction, or restenosis after coronary
      angioplasty. Plasma folate concentrations in control subjects (n = 90) and
      patients (n = 208) showed closely similar distributions. CONCLUSIONS: Although it
      is accepted that moderate hyperhomocysteinemia significantly increases the risk
      for coronary, cerebrovascular, and peripheral vascular diseases, our data suggest
      that a mutation of the MTHFR gene, which has been associated with a thermolabile
      form of the enzyme and with hyperhomocysteinemia in subjects with plasma folate
      below the median, does not appear to be significantly associated with risk for
      premature coronary artery disease or for restenosis after coronary angioplasty.

PMID- 8994412
TI  - Cost-effectiveness of populationwide educational approaches to reduce serum
      cholesterol levels.
AB  - BACKGROUND: The aim of the present study was to estimate the cost-effectiveness
      of populationwide approaches to reduce serum cholesterol levels in the US adult
      population. METHODS AND RESULTS: This cost-effectiveness analysis was made from
      data from the literature and the Coronary Heart Disease Policy Model and was
      based on the US population age 35 to 84 years. Study interventions were
      populationwide programs to reduce serum cholesterol levels with costs and
      cholesterol-lowering effects similar to those reported from the Stanford Three
      Community Study, the Stanford Five-City Project, and in North Karelia, Finland.
      The main outcome measures were cost-effectiveness ratios, defined as the change
      in projected cost divided by the change in projected life-years when the
      population receives the intervention compared with the population without the
      intervention. A populationwide program with the costs ($4.95 per person per year)
      and cholesterol-lowering effects (an average 2% reduction in serum cholesterol
      levels) of the Stanford Five-City Project would prolong life at an estimated cost
      of only $3200 per year of life saved. Under a wide variety of assumptions, a
      populationwide program would achieve health benefits at a cost equivalent to that
      of many currently accepted medical interventions. Such programs would also
      lengthen life and save resources under many scenarios, especially if the program
      affected persons with preexisting heart disease or altered other coronary risk
      factors. CONCLUSIONS: Populationwide programs should be part of any national
      health strategy to reduce coronary heart disease.

PMID- 8994413
TI  - Unfavorable effect of smoking on the elastic properties of the human aorta.
AB  - BACKGROUND: Smoking is a major risk factor for cardiovascular morbidity and
      mortality. Because previous studies have shown that smoking affects vasomotor
      response, we hypothesized that smoking may also acutely alter aortic elastic
      properties. METHODS AND RESULTS: We studied 40 male current and long-term smokers
      who underwent diagnostic cardiac catheterization for chest-pain evaluation.
      Twenty subjects (age, 48 +/- 2 years, mean +/- SEM) were randomly assigned to
      smoking and 20 (age, 47 +/- 2 years) to sham smoking studies. Aortic elastic
      properties were studied with the determination of the aortic pressure-diameter
      relation before smoking, every minute for the first 5 minutes after the
      initiation of smoking or sham smoking, and every 5 minutes for the following 15
      minutes. Instantaneous diameter of the thoracic aorta was measured with a special
      ultrasonic dimension catheter developed in our laboratory and previously
      validated. Instantaneous aortic pressure was measured at the same site as was
      diameter with a Millar micromanometer. Smoking was associated with significant
      changes in the aortic pressure-diameter relation that denote deterioration of the
      elastic properties and were maintained during the whole study period: the slope
      of the pressure-diameter loop became steeper (baseline, 35.43 +/- 1.38; minute 1,
      45.26 +/- 1.65; peak at minute 10, 46.36 +/- 1.69 mm Hg/mm; P < .001) and aortic
      distensibility decreased (baseline, 2.08 +/- 0.12; minute 1, 1.60 +/- 0.08; nadir
      at minute 5, 1.54 +/- 0.07 x 10(-6) cm2.dyne-1; P < .001). In contrast, no
      changes in aortic elasticity indexes were observed with sham smoking.
      CONCLUSIONS: Smoking is associated with an acute deterioration of aortic elastic
      properties. This effect of smoking may contribute to the unfavorable consequences
      of smoking on the cardiovascular system.

PMID- 8994414
TI  - Effects of estrogen replacement therapy on the renin-angiotensin system in
      postmenopausal women.
AB  - BACKGROUND: Oral estrogen replacement therapy (ERT) is known to stimulate the
      synthesis of angiotensinogen. The effects of such therapy on renin, ACE, and
      aldosterone are less clear. This seems noteworthy, however, since further
      activation of the system could be disadvantageous to postmenopausal women who
      replace estrogen in the context of heart failure, coronary artery disease, or
      hypertension. METHODS AND RESULTS: Estrogen status and components of the renin
      angiotensin system were examined in a population-based sample of postmenopausal
      women and age-matched men. Renin was quantified immunoradiometrically, ie,
      independent of substrate abundance; aldosterone, angiotensinogen, and ACE
      activity were determined by standard methods. Renin levels were lower in women
      with ERT (n = 107; 12.0 +/- 0.7 mU/L) compared with women without ERT (n = 223;
      16.6 +/- 0.9 mU/L; P = .001) or men (n = 342, 20.5 +/- 1.5 mU/L, P < .0001). In
      contrast, angiotensinogen was higher in women with ERT (1.36 +/- 0.08 mg/L)
      compared with women without ERT (1.03 +/- 0.02 mg/L; P < .0001) or compared with
      men (0.97 +/- 0.01 mg/L; P < .0001). Renin suppression was seen with either oral
      or transdermal estrogen replacement (-30% and -31%, respectively; both P < .001).
      In contrast, the increase of angiotensinogen was limited to women taking oral
      estrogens (+58%, P < .001). Multivariate analysis revealed that these estrogen
      effects were independent of age, body mass index, blood pressure, and/or
      antihypertensive medication. Finally, only marginal differences between groups
      were observed for serum ACE activity and aldosterone. CONCLUSIONS: Aside from a
      well-documented induction of angiotensinogen, ERT is related to a substantial
      suppression of renin, a phenomenon that might have received little attention
      because of widely used indirect measurements of the hormone.

PMID- 8994415
TI  - Antagonists of the mannose receptor and the LDL receptor-related protein
      dramatically delay the clearance of tissue plasminogen activator.
AB  - BACKGROUND: Clinical application of tissue plasminogen activator (TPA) as a
      fibrinolytic agent is complicated by its rapid clearance from the bloodstream,
      which is caused by TPA liver uptake. The mannose receptor on endothelial liver
      cells and the LDL receptor-related protein (LRP) on parenchymal liver cells were
      reported to contribute to liver uptake. METHODS AND RESULTS: In this study, we
      addressed whether TPA clearance can be delayed by inhibiting receptor-mediated
      endocytosis of TPA. A series of cluster mannosides was synthesized, and their
      affinity for the mannose receptor was determined. A cluster mannoside carrying
      six mannose groups (M6L5) displayed a subnanomolar affinity for the mannose
      receptor (Ki = 0.41 +/- 0.09 nmol/L). Preinjection of M6L5 (1.2 mg/kg) reduced
      the clearance of 125I-TPA in rats by 60% because of specific inhibition of the
      endothelial cell uptake. The low toxicity of M6L5, combined with its accessible
      synthesis and high specificity for the mannose receptor, makes it a promising
      agent to improve the pharmacokinetics of TPA. Blockade of LRP by 39-kD receptor
      associated protein (GST-RAP) also inhibited TPA clearance by 60%. Finally,
      combined preinjection of M6L5 and GST-RAP almost completely abolished reduced
      liver uptake of TPA and delayed its clearance by a factor of 10. CONCLUSIONS: It
      can be concluded that (1) the mannose receptor and LRP appear to be the sole
      major receptors responsible for TPA clearance and (2) therapeutic levels of TPA
      can be maintained for a prolonged time span by coadministration of the
      aforementioned receptor antagonists.

PMID- 8994416
TI  - Sustained prognostic value of dobutamine stress echocardiography for late cardiac
      events after major noncardiac vascular surgery.
AB  - BACKGROUND: Late cardiac events after major noncardiac vascular surgery are an
      important cause of morbidity and mortality. We studied the prognostic value of
      preoperative dobutamine stress echocardiography, relative to clinical risk
      assessment, in predicting late cardiac events. METHODS AND RESULTS: Three hundred
      sixteen patients undergoing major vascular surgery were studied. All patients
      underwent clinical evaluation for the presence of cardiac risk factors (smoking,
      hypertension, angina, diabetes, history of heart failure, previous infarction,
      and age > 70 years) and dobutamine stress echocardiography. Left ventricular wall
      motion was evaluated at rest, and the extent and severity of stress-induced new
      wall motion abnormalities were quantified. The heart rate threshold at which new
      wall motion abnormalities occurred was noted. Patients were followed
      perioperatively and for 19 +/- 11 months postoperatively, and the occurrence of
      cardiac events was noted. Univariate and multivariate Cox proportional hazards
      regression models were used to identify predictors of late cardiac events. Thirty
      two cardiac events occurred (11 cardiac deaths, 11 nonfatal myocardial
      infarctions, and 10 incidents of unstable angina). By multivariate regression
      analysis, the occurrence of extensive (three or more segments) or limited (one or
      two segments) stress-induced new wall motion abnormalities and previous
      infarction independently predicted late cardiac events, elevating the risk by 6.5
      , 2.9-, and 3.8-fold, respectively. The severity of ischemia during stress and
      the heart rate threshold for ischemia were not independently predictive.
      CONCLUSIONS: Patients with a history of myocardial infarction or stress-induced
      ischemia have a high risk of fatal and nonfatal cardiac events after vascular
      surgery. Patients with both a history of infarction and extensive stress-induced
      ischemia are at especially high risk and deserve intensive management.

PMID- 8994417
TI  - Arterial and venous thrombosis is not associated with the 4G/5G polymorphism in
      the promoter of the plasminogen activator inhibitor gene in a large cohort of US
      men.
AB  - BACKGROUND: The 4G allele of the 4G/5G polymorphism in the promoter of the
      plasminogen activator inhibitor (PAI-1) gene is associated with increased PAI-1
      activity. In a small group of young Swedish men, this allele has been reported to
      predict risk of myocardial infarction. Whether this polymorphism increases risk
      of arterial and venous thrombosis among middle-aged men is unknown. METHODS AND
      RESULTS: Among 14916 men 40 to 84 years old participating in the Physicians'
      Health Study who provided baseline blood samples for DNA analysis, 374 suffered
      first myocardial infarction and 121 had venous thromboembolism during 8.6 years
      of follow-up. Distributions of the 4G/5G polymorphism in the PAI-1 gene promoter
      were assessed in these men as well as in a sample of study participants matched
      on age and smoking who did not develop vascular occlusion during the prospective
      follow-up period. The distributions of the 4G/4G, 4G/5G, and 5G/5G genotypes
      among men who developed myocardial infarction (0.27, 0.51, 0.22; P = .7) or
      venous thromboembolism (0.30, 0.49, 0.21; P = .5) were virtually identical to
      those of men who remained free of vascular disease (0.27, 0.50, 0.23). Thus, the
      relative risk of future thrombosis among those with the 4G/4G genotype compared
      with those without the 4G/4G genotype was 1.02 (95% CI, 0.8 to 1.3). There was no
      effect modification by age, smoking status, family history of premature
      thrombosis, history of hypertension, hypercholesterolemia, or aspirin use.
      CONCLUSIONS: These data indicate that the 4G/5G polymorphism in the promoter of
      the PAI-1 gene is not a major pathogenetic risk factor for arterial or venous
      thrombosis among middle-aged men.

PMID- 8994418
TI  - Prothrombotic effects of erythrocytes on platelet reactivity. Reduction by
      aspirin.
AB  - BACKGROUND: Aspirin effectively reduces the incidence of secondary vascular
      occlusive events in only 25% of patients. Low-dose aspirin as currently used
      blocks platelet production of prothrombotic thromboxane A2 and allows endothelial
      synthesis of antithrombotic prostacyclin. This regimen minimizes gastrointestinal
      toxicity. We previously showed that intact erythrocytes markedly enhance platelet
      reactivity. Therefore we investigated whether supplementation of low-dose aspirin
      with a single high dose at 2-week intervals could more effectively block
      erythrocyte promotion of platelet reactivity. METHODS AND RESULTS: Effects of
      different aspirin regimens on erythrocyte enhancement of platelet reactivity in
      normal volunteers were measured with the use of an assay that evaluates both
      platelet activation and recruitment. After 15 days of daily ingestion of 50 mg
      aspirin, reactivity of platelets alone was inhibited. However, erythrocyte
      promotion of platelet activation and recruitment was only inhibited by
      approximately 50% and persisted in the total absence of thromboxane synthesis. In
      contrast, if 50 mg/d aspirin was preceded by a single loading dose of 500 mg
      aspirin, the erythrocyte prothrombotic effect was strongly inhibited
      (approximately 90%) for 2 to 3 weeks. However, over time, erythrocytes "escaped"
      from this inhibition, and once again became prothrombotic, even on a daily
      regimen of 50 mg aspirin. CONCLUSIONS: For clinical purposes, we recommend a
      loading dose of aspirin (500 mg), followed by daily administration of 50 mg. The
      loading dose should be repeated at 2-week intervals. This regimen blocks recovery
      of the erythrocyte capacity to promote platelet reactivity and may amplify the
      therapeutic potential of aspirin in cardiovascular disease.

PMID- 8994419
TI  - Small, dense low-density lipoprotein particles as a predictor of the risk of
      ischemic heart disease in men. Prospective results from the Quebec Cardiovascular
      Study.
AB  - BACKGROUND: Case-control studies have reported that patients with ischemic heart
      disease (IHD) have a higher proportion of small, dense LDL particles than do
      healthy control subjects. The extent to which the risk attributed to small LDL
      particles may be independent of concomitant variations in plasma lipoprotein
      lipid concentrations remains to be clearly determined, however, particularly
      through prospective studies. METHODS AND RESULTS: Baseline characteristics were
      obtained in 2103 men initially free of IHD, among whom 114 developed IHD during a
      5-year follow-up period. These 114 case patients were matched with healthy
      control subjects for age, body mass index, smoking habits, and alcohol intake.
      LDL peak particle diameter (PPD) was measured a posteriori in 103 case-control
      pairs by nondenaturing gradient gel electrophoresis of whole plasma. Conditional
      logistic regression analysis of the case-control status revealed that men in the
      first tertile of the control LDL-PPD distribution (LDL-PPD < or = 25.64 nm) had a
      3.6-fold increase in the risk of IHD (95% CI, 1.5 to 8.8) compared with those in
      the third tertile (LDL-PPD > 26.05 nm). Statistical adjustment for concomitant
      variations in LDL cholesterol, triglycerides, HDL cholesterol, and apolipoprotein
      B concentrations had virtually no impact on the relationship between small LDL
      particles and the risk of IHD. CONCLUSIONS: These results represent the first
      prospective evidence suggesting that the presence of small, dense LDL particles
      may be associated with an increased risk of subsequently developing IHD in men.
      Results also suggest that the risk attributed to small LDL particles may be
      partly independent of the concomitant variation in plasma lipoprotein-lipid
      concentrations.

PMID- 8994420
TI  - Single LDL apheresis improves endothelium-dependent vasodilatation in
      hypercholesterolemic humans.
AB  - BACKGROUND: Although long-term lipid-lowering therapy improves endothelium
      dependent vasodilatation in humans, it remains unknown whether the short-term
      removal of LDL per se ameliorates endothelial dysfunction. METHODS AND RESULTS:
      To examine the effects of a single session of LDL apheresis on endothelial
      function in patients with hypercholesterolemia, we measured forearm blood flow
      (FBF) by strain-gauge plethysmography before and after single LDL apheresis while
      infusing acetylcholine (ACh; 4 to 24 micrograms/min) and sodium nitroprusside
      (SNP; 0.2 to 1.2 micrograms/min). The single session of LDL apheresis reduced
      total LDL (from 142.2 +/- 15.0 to 32.6 +/- 5.0 mg/mL, P < .0005) and oxidized LDL
      (from 111.6 +/- 22.8 to 30.0 +/- 5.4 ng/mL, P < .005). Although ACh and SNP
      increased FBF dose-dependently before and after LDL apheresis, the endothelium
      dependent vasodilatation responses to ACh were significantly augmented (P < .01)
      after the single session of LDL apheresis without changes in the endothelium
      independent vasodilatation responses to SNP. The plasma levels of total and
      oxidized LDL correlated with the degree of ACh-induced vasodilatation.
      Furthermore, the local production of nitrate/nitrite, metabolites of NO, during
      ACh infusion was significantly (P < .05) augmented by LDL apheresis, and there
      was a significant correlation between the degree of ACh-induced vasodilatation
      and the production in nitrate/nitrite (r = .99, P < .0005). CONCLUSIONS: We
      demonstrated that even a single session of LDL apheresis with the reduction of
      total LDL and oxidized LDL improved endothelial function. Our results suggest
      that total LDL and/or oxidized LDL may directly impair endothelial function in
      the human forearm vessel.

PMID- 8994421
TI  - Effect of the direct nitric oxide donors linsidomine and molsidomine on
      angiographic restenosis after coronary balloon angioplasty. The ACCORD Study.
      Angioplastic Coronaire Corvasal Diltiazem.
AB  - BACKGROUND: Nitric oxide (NO) donors, in addition to their vasodilator effect,
      decrease platelet aggregation and inhibit vascular smooth muscle cell
      proliferation. These actions could have beneficial effects on restenosis after
      coronary balloon angioplasty. METHODS AND RESULTS: In a prospective multicenter,
      randomized trial, 700 stable coronary patients scheduled for angioplasty received
      direct NO donors (infusion of linsidomine followed by oral molsidomine) or oral
      diltiazem. Treatment was started before angioplasty and continued until 12 to 24
      hours before follow-up angiography at 6 months. The primary study end point was
      minimal lumen diameter, assessed by quantitative coronary angiography, 6 months
      after balloon angioplasty. Clinical variables were well matched in both groups.
      However, despite intracoronary administration of isosorbide dinitrate, the
      reference diameter in the NO donor group was significantly greater than in the
      diltiazem group on the preangioplasty, postangioplasty, and follow-up angiograms.
      Pretreatment with an NO donor was associated with a modest improvement in the
      immediate angiographic result compared with pretreatment with diltiazem (minimum
      luminal diameter, 1.94 versus 1.81 mm; P = .001); this improvement was maintained
      at the 6-month angiographic follow-up (minimal lumen diameter, 1.54 versus 1.38
      mm; P = .007). The extent of late luminal narrowing did not differ significantly
      between groups (loss index in the NO donor and diltiazam groups, 0.35 +/- 0.78
      and 0.46 +/- 0.74, respectively; P = .103). Restenosis, defined as a binary
      variable (> or = 50% stenosis), occurred less often in the NO donor group (38.0%
      versus 46.5%; P = .026). Combined major clinical events (death, nonfatal
      myocardial infarction, and coronary revascularization) were similar in the two
      groups (32.2% versus 32.4%). CONCLUSIONS: Treatment with linsidomine and
      molsidomine was associated with a modest improvement in the long-term
      angiographic result after angioplasty but had no effect on clinical outcome. The
      improved angiographic result related predominantly to a better immediate
      procedural result, because late luminal loss did not differ significantly between
      groups.

PMID- 8994422
TI  - Dobutamine enhances cardiodepressant effects of receptor-mediated coronary
      endothelial stimulation.
AB  - BACKGROUND: In humans, intracoronary infusion of substance P reduces left
      ventricular end-systolic pressure and left ventricular peak systolic pressure
      because of earlier onset of left ventricular relaxation induced by paracrine
      myocardial action of mediators released from the coronary endothelium. The
      present study investigated in humans the effects of beta-adrenergic stimulation,
      which also induces earlier left ventricular relaxation, on the left ventricular
      myocardial contractile response to intracoronary infusion of substance P. METHODS
      AND RESULTS: Data were obtained in 13 patients after cardiac transplantation and
      in 3 patients with dilated nonischemic cardiomyopathy. Microtip left ventricular
      pressure recordings were obtained during a 5-minute intracoronary infusion of
      substance P (20 pmol/min) under control conditions and then repeated during
      concurrent intravenous administration of dobutamine. In the presence of
      dobutamine, intracoronary substance P caused a greater fall in left ventricular
      end-systolic pressure (transplantation control, -9 +/- 11 versus transplantation
      dobutamine, -20 +/- 18 mm Hg [P < .05]; cardiomyopathy control, -4 +/- 1 versus
      cardiomyopathy dobutamine, -10 +/- 3 mm Hg [P < .05]) and in left ventricular
      peak systolic pressure (transplantation control, -14 +/- 10 versus
      transplantation dobutamine, -30 +/- 22 mm Hg [P < .01]; cardiomyopathy control, 
      9 +/- 7 versus cardiomyopathy dobutamine, -15 +/- 6 mm Hg [P = .1]). CONCLUSIONS:
      Dobutamine enhances the cardiodepressant effect on myocardial contractile
      performance of receptor-mediated coronary endothelial stimulation in transplant
      recipients and in patients with dilated nonischemic cardiomyopathy. This
      enhancement could result from a potentiating interaction of the relaxation
      hastening effect exerted by beta-adrenergic stimulation and by mediators released
      from the coronary endothelium, such as nitric oxide.

PMID- 8994423
TI  - C-reactive protein colocalizes with complement in human hearts during acute
      myocardial infarction.
AB  - BACKGROUND: Rises in circulating C-reactive protein (CRP), the prototypical acute
      phase protein in humans, correlate with clinical outcome in patients with
      myocardial ischemia and infarction. We hypothesized that these correlations might
      reflect active participation of CRP in the local inflammatory response ensuing in
      the jeopardized myocardium because on binding to a ligand, CRP is able to
      activate the classic pathway of complement, and in addition, complement
      activation has been shown to occur locally in infarcted myocardium. METHODS AND
      RESULTS: To verify our hypothesis, we investigated localization of CRP in
      relation to deposition of complement in tissue specimens of infarcted and healthy
      heart tissue obtained from 17 patients who had died after acute myocardial
      infarction. CRP was found to be deposited only in infarcted regions and not in
      normal-appearing areas of the myocardium, being colocalized with depositions of
      C4 and C3 activation fragments of the complement system. Deposition of CRP and
      complement in infarcted myocardium appeared to be time dependent, because it was
      found in all infarctions except for one of young age (< 12 hours old) and two of
      greater age (> 1 year old), whereas another tissue specimen of an infarct < 12
      hours old showed only moderate but positive staining for both CRP and complement
      in comparison with older infarctions. CONCLUSIONS: We conclude that in humans,
      CRP may localize in infarcted heart tissue and suggest that this acute-phase
      protein promotes local complement activation, and hence tissue damage, in acute
      myocardial infarction.

PMID- 8994424
TI  - Coronary vascular nitric oxide activity in hypertension and hypercholesterolemia.
      Comparison of acetylcholine and substance P.
AB  - BACKGROUND: Whether the abnormal responses of the human coronary circulation to
      acetylcholine in patients with hypertension and hypercholesterolemia extend to
      other, nonmuscarinic stimulators of the endothelium and whether this signifies a
      specific abnormality of NO is not known. METHODS AND RESULTS: We studied 26
      patients with angiographically normal coronary arteries, 10 without risk factors,
      and 16 with either hypertension (n = 9) and/or hypercholesterolemia (n = 10).
      Dose-response curves were performed with acetylcholine, substance P, and sodium
      nitroprusside before and after NG-monomethyl-L-arginine (L-NMMA). Substance P
      produced predominantly epicardial coronary dilation, whereas the dilating effect
      of acetylcholine was mainly microvascular. There was no correlation between the
      responses to the two drugs. L-NMMA did not affect the response to sodium
      nitroprusside, but it suppressed dilation in response to both substance P and
      acetylcholine, suggesting that the latter promote bioavailability of NO from the
      coronary vascular endothelium. Compared with patients without risks, those with
      hypercholesterolemia and hypertension had significantly reduced vasodilation with
      substance P: 21% versus 12.6% (P = .004) increase in epicardial coronary diameter
      and 35% versus 19% (P < .05) decrease in vascular resistance. Similar differences
      were noted with acetylcholine but not with sodium nitroprusside or adenosine.
      Epicardial and microvascular dilations with substance P or acetylcholine after L
      NMMA were similar in patients with and without risk factors, indicating that the
      reduced effect of endothelium-dependent vasodilators in those with hypertension
      and hypercholesterolemia is due to diminished NO activity. CONCLUSIONS: (1)
      Substance P- and acetylcholine-induced coronary vasodilation, like that to
      acetylcholine, is at least partly due to stimulation of NO activity, indicating
      that the dysfunction of the coronary vascular endothelial cell layer is not
      restricted to muscarinic receptors. (2) Hypertension and hypercholesterolemia are
      associated with depression of both basal and pharmacologically stimulated
      bioavailability of NO.

PMID- 8994425
TI  - Long-term implications of reocclusion on left ventricular size and function after
      successful thrombolysis for first anterior myocardial infarction.
AB  - BACKGROUND: Successful thrombolysis can prevent left ventricular dilatation after
      acute myocardial infarction. However, in almost 30% of patients, reocclusion
      occurs. The aim of this study was to assess the long-term implications of
      reocclusion on left ventricular size and function. METHODS AND RESULTS: Fifty-six
      patients were studied with two-dimensional echocardiography at baseline (2 +/-
      1.6 days) and 5.0 +/- 1.4 years after first anterior myocardial infarction. All
      patients (a subset of those enrolled in the APRICOT trial) had a patent infarct
      related artery when studied < 48 hours after thrombolysis and underwent repeat
      coronary angiography at 3 months. Baseline characteristics were comparable in
      patients with (n = 17) and without reocclusion (n = 39). Left ventricular volume
      indexes were stable in patients without reocclusion. Patients with reocclusion,
      however, showed a significant increase in end-diastolic volume index (EDVI; P =
      .008) and end-systolic volume index (ESVI; P = .039). Furthermore, patients
      without reocclusion demonstrated improvement in wall motion score index (WMSI; P
      = .0001) and ejection fraction (EF; P = .016), whereas patients with reocclusion
      did not. After 5 years, patients with reocclusion had significantly larger volume
      indexes (EDVI, 99 +/- 41 versus 76 +/- 22 mL/m2, P = .007; ESVI, 59 +/- 40 versus
      39 +/- 20 mL/m2, P = .017) and more compromised left ventricular function (WMSI,
      1.63 +/- 0.33 versus 1.39 +/- 0.32, P = .013; EF, 45 +/- 13% versus 51 +/- 11%, P
      = .077) than patients without reocclusion. Multivariate analysis identified
      baseline WMSI and reocclusion as significant independent predictors of left
      ventricular dilatation. CONCLUSIONS: Reocclusion of the infarct-related artery
      within 3 months of successful thrombolysis is associated with left ventricular
      dilatation and is detrimental to functional recovery of left ventricular function
      5 years after first anterior myocardial infarction.

PMID- 8994426
TI  - Effect of nonspecific binding to plasma proteins on the antithrombin activities
      of unfractionated heparin, low-molecular-weight heparin, and dermatan sulfate.
AB  - BACKGROUND: Nonspecific binding to plasma proteins decreases the anti-factor Xa
      (anti-Xa) activity of unfractionated heparin (UFH) but not that of low-molecular
      weight heparin (LMWH). However, plasma proteins could influence the anti-thrombin
      (anti-IIa) activity of LMWH. To explore this possibility, we compared the effects
      of plasma proteins on the anti-IIa activities of UFH and LMWH. We also examined
      their effects on the anti-IIa activity of dermatan sulfate (DS) because, like
      UFH, DS binds to plasma proteins. METHODS AND RESULTS: There was almost complete
      recovery of anti-IIa activity when UFH, LMWH, or DS was added to plasma from each
      of 20 healthy volunteers. The addition of a chemically modified heparin with low
      affinity for antithrombin III to plasma containing UFH increased the anti-IIa
      activity in a concentration-dependent fashion by displacing UFH from plasma
      proteins. In contrast, addition of low-affinity heparin had no effect on the anti
      IIa activity of LMWH. LMWH does not bind to plasma proteins because the bulk of
      the LMWH chains are < 6000 D, and only heparin fractions > 6000 D bind
      nonspecifically to plasma proteins. As further evidence that plasma proteins do
      not influence the anti-IIa activity of LMWH, the rate of thrombin inhibition in
      plasma in the presence of LMWH is virtually identical to that in buffer
      containing physiological amounts of the major antithrombins. In contrast, with
      UFH or DS, the rate of thrombin inhibition is twofold slower in plasma than in
      buffer. CONCLUSIONS: Nonspecific binding of UFH to plasma proteins most likely
      contributes to the variable anti-IIa response to UFH in patients with
      thromboembolic disease. Although DS also binds to plasma proteins, the clinical
      significance of this finding is unclear. In contrast, because LMWH does not bind
      to plasma proteins, the anti-IIa activity of LMWH should be just as predictable
      as its anti-Xa activity.

PMID- 8994427
TI  - Different effects of calcium antagonists, nitrates, and beta-blockers on platelet
      function. Possible importance for the treatment of unstable angina.
AB  - BACKGROUND: The three major classes of antianginal drug all inhibit platelet
      aggregation at high concentrations in vitro, but detecting clinically relevant
      effects has proved to be more difficult. We used whole-blood flow cytometry, a
      sensitive method that allows direct measurement of activation antigens on the
      surface of individual platelets in whole unfixed blood, to evaluate the effect of
      representative antianginal drugs on platelet function in vivo in healthy
      volunteers. METHODS AND RESULTS: The effects of glyceryl trinitrate (GTN),
      amlodipine, and atenolol were studied in nine normal volunteers. Fibrinogen
      binding to activated GP IIb/IIIa and expression of P-selectin, GP Ib, and GP
      IIb/IIIa on the platelet surface were measured. In addition, fibrinogen binding
      and P-selectin expression were measured in response to ex vivo stimulation with
      the agonists ADP and thrombin. The three drugs had very different effects on
      platelets. GTN inhibited platelet fibrinogen binding and expression of P-selectin
      at rest and in response to agonist stimulation, whereas amlodipine enhanced P
      selectin expression and atenolol increased fibrinogen binding in response to
      agonists. Atenolol did not block the stimulatory effects of epinephrine on ADP
      induced platelet activation. GTN neutralized the proactivatory effects of
      amlodipine, whereas the effects of atenolol and amlodipine were not additive.
      CONCLUSIONS: The three main classes of antianginal medication have different and
      possible clinically relevant effects on platelet behavior in vivo, nitrates
      causing inhibition of aggregation (fibrinogen binding) and degranulation (P
      selectin expression), calcium antagonists enhancing degranulation, and beta
      blockers enhancing aggregation.

PMID- 8994428
TI  - Viral infection of the myocardium in endocardial fibroelastosis. Molecular
      evidence for the role of mumps virus as an etiologic agent.
AB  - BACKGROUND: Endocardial fibroelastosis, previously a common disease of children,
      often resulted in congestive heart failure and death. Virus-induced myocarditis
      was the suspected first step in the pathogenesis of the disease, with
      enteroviruses and mumps virus considered potential causes. Direct evidence for
      their involvement was limited, however, and during the past two decades, a
      significant decline in the incidence of endocardial fibroelastosis occurred.
      Recently, we demonstrated polymerase chain reaction to be a rapid and sensitive
      method for identification of the viral genome in the myocardium of patients with
      myocarditis and dilated cardiomyopathy. The purpose of this study was to analyze
      myocardial samples of patients with endocardial fibroelastosis for the viral
      genome. METHODS AND RESULTS: Myocardial samples from 29 patients with autopsy
      proven endocardial fibroelastosis were analyzed for viral genome (enterovirus,
      adenovirus, mumps, cytomegalovirus, parvovirus, influenza, herpes simplex virus)
      by use of polymerase chain reaction or reverse transcriptase-polymerase chain
      reaction. In 90% of samples, the viral genome was amplified; > 70% of the samples
      were positive for mumps viral RNA, while 28% amplified adenovirus. In contrast,
      only 1 of 65 control samples amplified a virus (enterovirus). Two regions of
      mumps virus were amplified: the nucleocapsid gene and the polymerase-associated
      protein gene. Interestingly, only 3 of the 21 samples that were positive for
      mumps RNA were positive with both sets of primers, indicating that the
      persistence of mumps virus in the myocardium may be related to the selection of
      defective virus mutants. CONCLUSIONS: These data suggest an etiologic role for
      viral infection in endocardial fibroelastosis, supporting the hypothesis that
      endocardial fibroelastosis is a sequela of a viral myocarditis, in particular of
      that due to mumps virus.

PMID- 8994429
TI  - Recognition of acute cardiac allograft rejection from serial integrated
      backscatter analyses in human orthotopic heart transplant recipients. Comparison
      with conventional echocardiography.
AB  - BACKGROUND: Previous studies showed that moderate and severe acute cardiac
      rejection (AR) but not mild AR is associated with significant myocardial acoustic
      changes. This study examines whether serial measurements of end-diastolic two
      dimensional integrated backscatter (2D-IB) enhance the diagnostic potential of
      ultrasonic tissue analysis in AR. METHODS AND RESULTS: Serial endomyocardial
      biopsies, conventional echocardiograms, and parasternal long-axis radiofrequency
      signals for determination of posterior wall and septal 2D-IB were performed in 52
      transplant patients. Histology showed no AR in 155 biopsy samples, AR grade 1A in
      25, AR grade 1B/2 in 27, and AR grade 3A/3B in 13. Whereas no significant 2D-IB
      changes occurred between AR-free studies and during AR grade 1A, posterior wall
      and septal 2D-IB increased during AR grade 1B/2 from -47.80 +/- 4.36 to -42.97 +/
      5.11 dB and from -36.72 +/- 7.45 to -32.52 +/- 7.98 dB (P < .001 and P < .05,
      respectively) and during AR grade 3A/3B from -47.96 +/- 4.74 to -38.25 +/- 5.32
      dB and from -37.92 +/- 5.87 to -31.01 +/- 4.62 dB (P < .001 and P < .01,
      respectively). Changes in posterior wall and septal 2D-IB were greater during AR
      grade 3A/3B than during AR grade 1B/2 (P < .01 and P < .05). Increases of 1.5 dB
      in posterior wall or septal 2D-IB indicated AR grades > or = 1B with
      sensitivities of 88% and 83% and specificities of 89% and 85%; posterior wall and
      septal 2D-IB increases of 5.5 and 3.8 dB identified AR grades > or = 3A with
      sensitivities of 92% and 79% and specificities of 90% and 84%. Although a weak
      inverse correlation between posterior wall and septal 2D-IB changes and posterior
      wall and septal thickening (r = .41 and r = .39, both P < .001) and fractional
      diameter shortening (r = .35, P < .001) was found, significant 2D-IB increases
      also occurred in some rejecting patients with unaltered contraction. CONCLUSIONS:
      Increases in end-diastolic posterior wall and septal 2D-IB in serial studies
      permit reliable identification not only of moderate and severe AR but also of
      mild AR. Because 2D-IB increase significantly more in AR with myocyte damage than
      without such damage, an estimate of AR severity appears feasible. Significant
      myocardial acoustic changes during AR may occur independently of changes in
      contractile performance.

PMID- 8994430
TI  - Noninvasive assessment of the ventricular relaxation time constant (tau) in
      humans by Doppler echocardiography.
AB  - BACKGROUND: The time constant of ventricular relaxation (tau) is a quantitative
      measure of diastolic performance requiring intraventricular pressure recording.
      This study validates in humans an equation relating tau to left ventricular
      pressure at peak -dP/dt (P0), pressure at mitral valve opening (PMV), and
      isovolumic relaxation time (IVRTinv). The clinically obtainable parameters peak
      systolic blood pressure (Ps), mean left atrial pressure (PLA), and Doppler
      derived IVRT (IVRTDopp) are then substituted into this equation to obtain tau
      Dopp noninvasively. METHODS AND RESULTS: High-fidelity left atrial and left
      ventricular pressure recordings with simultaneous Doppler by transesophageal
      echocardiography were obtained from 11 patients during cardiac surgery. Direct
      curve fitting to the left ventricular pressure trace by Levenberg-Marquardt
      regression assuming a zero asymptote generated tau LM, the "gold standard"
      against which tau calc (IVRT inv/[ln(P0)-ln(PMV)]) and tau Dopp [IVRTDopp/[ln(Ps)
      ln(PLA)]] were compared. For 123 cycles analyzed in 18 hemodynamic states, mean
      tau LM was 53.8 +/- 12.9 ms. tau calc (51.5 +/- 11 ms) correlated closely with
      this standard (r = .87, SEE = 5.5 ms). Noninvasive tau Dopp (43.8 +/- 11 ms)
      underestimated tau LM but exhibited close linear correlation (n = 88, r = .75,
      SEE = 7.5 ms). Substituting PLA = 10 mm Hg into the equation yielded tau 10 (48.7
      +/- 15 ms), which also closely correlated with the standard (r = .62, SEE = 11.6
      ms). CONCLUSIONS: The previously obtained analytical expression relating IVRT,
      invasive pressures, and tau is valid in humans. Furthermore, a more clinically
      obtainable, noninvasive method of obtaining tau also closely predicts this
      important measure of diastolic function.

PMID- 8994431
TI  - Modification of human left ventricular relaxation by small-amplitude, phase
      controlled mechanical vibration on the chest wall.
AB  - BACKGROUND: Direct clinical manipulation to improve an impairment of left
      ventricular (LV) relaxation has not been reported. We investigated whether the LV
      relaxation rate in humans could be modulated by phase-controlled mechanical
      vibration applied to the patient's anterior chest wall and whether there are some
      quantitative differences in the responses of normal (N), hypertrophied (H), and
      failing (F) ventricle. METHODS AND RESULTS: In 46 patients (N, 10; H, 18
      [hypertrophic cardiomyopathy]; F, 18 [heart failure]), the vibrator was attached
      to the precordium and a 50-Hz, 2-mm sinusoidal mechanical vibration was applied,
      with the timing restricted from the onset of isovolumic relaxation to end
      diastole during cardiac catheterization. Heart rate and peak LV pressure showed
      no difference with vibration. However, in all patients, precordial vibration
      caused an acceleration of the LV pressure fall. The magnitude of the induced
      reduction of the time constant of LV pressure decay (delta T) was larger (P <
      .01) in H and F than in N (4.6 +/- 2.3, 4.0 +/- 1.6, and 0.6 +/- 1.5 ms for H, F,
      and N, respectively). Delta T correlated strongly with the magnitude of impaired
      relaxation and the magnitude of transmitted vibration to the ventricle.
      CONCLUSIONS: Phase-controlled, small-amplitude vibration on the chest wall can
      directly modulate LV relaxation rate, especially in those with hypertrophy or
      failing ventricle.

PMID- 8994432
TI  - Elevations of cardiac troponin I associated with myocarditis. Experimental and
      clinical correlates.
AB  - BACKGROUND: Endomyocardial biopsy is currently the standard method used to
      diagnose myocarditis. However, it is invasive and has a low diagnostic yield.
      Because the histological diagnosis of myocarditis requires the presence of
      myocyte injury, we sought to determine whether measurement of cardiac troponin I
      (cTnI), which is a serum marker with high sensitivity and specificity for cardiac
      myocyte injury, could aid in the diagnosis of myocarditis. METHODS AND RESULTS:
      To validate this approach, cTnI values were first measured in mice with
      autoimmune myocarditis. cTnI values were elevated in 24 of 26 mice with
      myocarditis but were not elevated in any of the control animals (P < .001). Next,
      cTnI values were measured in the sera from 88 patients referred to the
      Myocarditis Treatment Trial and were compared with creatine kinase-MB (CK-MB)
      values measured in the same patients. cTnI values were elevated in 18 (34%) of 53
      patients with myocarditis and in only 4 (11%) of 35 patients without myocarditis
      (P = .01). In contrast, CK-MB values were elevated in only 3 (5.7%) of 53
      patients with myocarditis and 0 of 35 patients without myocarditis (P = .27).
      Thus, elevations of cTnI occurred more frequently than did elevations of CK-MB in
      patients with biopsy-proven myocarditis (P = .001). Importantly, elevations of
      cTnI in patients with myocarditis were significantly correlated with < or = 1
      month duration of heart failure symptoms (P = .02), suggesting that the majority
      of myocyte necrosis occurs early, and thus the window for diagnosis and treatment
      may be relatively brief. CONCLUSIONS: cTnI was superior to CK-MB for detection of
      myocyte injury in myocarditis, and cTnI elevations were substantially more common
      in the first month after the onset of heart failure symptoms.

PMID- 8994433
TI  - Increased cardiac adrenergic drive precedes generalized sympathetic activation in
      human heart failure.
AB  - BACKGROUND: Previous studies with radiotracer methods have indicated increases in
      cardiac norepinephrine (NE) and renal NE spillover in patients with severe
      congestive heart failure (CHF). However, data on the regional sympathetic profile
      in early stages of CHF are limited. In this study, sympathetic function in the
      heart, kidneys, and skeletal muscle was evaluated in patients with mild-to
      moderate CHF and compared with that in patients with severe CHF and healthy
      subjects. METHODS AND RESULTS: Total body and regional NE spillover from the
      heart and kidney was assessed with isotope dilution with steady state infusions
      of [3H]NE. Sympathetic nerve traffic to the skeletal muscle vascular bed (MSA)
      was recorded intraneurally. Cardiac NE spillover in patients with mild-to
      moderate CHF (n = 21) was increased threefold versus that in healthy subjects (n
      = 12, P < .05), whereas total body and renal NE spillover and MSA did not differ
      from those in healthy subjects. In the severe CHF group (n = 12), cardiac NE
      spillover was increased fourfold (P < .05), and total body and renal NE spillover
      and MSA were high compared with both mild-to-moderate CHF subjects and healthy
      subjects (P < .05 for both). Fractional extraction of [3H]NE across the heart was
      reduced by approximately 40% in both CHF groups versus control subjects (P <
      .05). CONCLUSIONS: These results indicate a selective increase in cardiac
      adrenergic drive (increased amounts of transmitter available at neuroeffector
      junctions) in patients with mild-to-moderate CHF. This increase appears to
      precede the augmented sympathetic outflow to the kidneys and skeletal muscle
      found in advanced CHF.

PMID- 8994434
TI  - ACE inhibitors promote nitric oxide accumulation to modulate myocardial oxygen
      consumption.
AB  - BACKGROUND: ACE inhibitors potentiate kinin-nitric oxide (NO)-dependent coronary
      vascular dilation, and NO can modulate myocardial oxygen consumption. Whether ACE
      inhibitors also affect myocardial O2 consumption has not been established.
      METHODS AND RESULTS: Production of nitrite, a metabolite of NO in aqueous
      solution, in coronary microvessels and O2 consumption in myocardium were
      quantified with the use of in vitro tissue preparations, the Greiss reaction, and
      a Clark-type O2 electrode. In coronary microvessels, kininogen (the precursor of
      kinin; 10 micrograms/mL) and three ACE inhibitors (captopril, enalaprilat, or
      ramiprilat; 10(-8) mol/L) increased nitrite production from 76 +/- 6 to 173 +/-
      15, 123 +/- 12, 125 +/- 12, and 153 +/- 12 pmol/mg, respectively (all P < .05).
      In myocardium, kininogen (10 micrograms/mL) and captopril, enalaprilat, or
      ramiprilat (10(-4) mol/L) reduced cardiac O2 consumption by 41 +/- 2%, 19 +/- 3%,
      25 +/- 2%, and 35 +/- 2%, respectively. The changes in both nitrite release and
      O2 consumption in vitro were blocked by N omega-nitro-L-arginine methyl ester or
      N omega-nitro-L-arginine, inhibitors of endogenous NO formation. The effects were
      also blocked by HOE 140, which blocks the bradykinin B2-kinin receptor, and
      serine protease inhibitors, which inhibit local kinin formation. CONCLUSIONS: Our
      data indicate that stimulation of local kinin formation by use of a precursor for
      kinin formation or inhibition of kinin degradation by use of ACE inhibitors
      increases NO formation and is important in the control of cardiac O2 consumption.
      Vasodilation and control of myocardial O2 consumption by NO may contribute
      importantly to the therapeutic actions of ACE inhibitors in cardiac disease
      states.

PMID- 8994435
TI  - Comparison of effective and ineffective target sites that demonstrate concealed
      entrainment in patients with coronary artery disease undergoing radiofrequency
      ablation of ventricular tachycardia.
AB  - BACKGROUND: Concealed entrainment has been useful in guiding catheter ablation of
      monomorphic ventricular tachycardia in patients with coronary artery disease.
      However, not all sites with concealed entrainment result in successful ablation
      of the targeted ventricular tachycardia. The purpose of this prospective study
      was to identify factors at sites that demonstrate concealed entrainment that
      differentiate effective from ineffective target sites. METHODS AND RESULTS: In 14
      consecutive patients with hemodynamically stable monomorphic ventricular
      tachycardia and coronary artery disease, radiofrequency ablation of 26
      ventricular tachycardias was performed. Ablation was attempted at 46 sites that
      demonstrated concealed entrainment. Twenty-five of the targeted ventricular
      tachycardias (96%) were successfully ablated. The positive predictive value of
      concealed entrainment for successful ablation was 54%; it increased to 72% in the
      presence of a stimulus-QRS interval/ventricular tachycardia cycle length ratio of
      < or = 70%, to 82% in the presence of a match of the stimulus-QRS and electrogram
      QRS interval, and to 89% in the presence of isolated mid diastolic potentials
      that could not be dissociated from ventricular tachycardia during entrainment.
      CONCLUSIONS: The positive predictive value of concealed entrainment for
      identification of successful ablation sites in patients with sustained
      ventricular tachycardia and coronary artery disease can be significantly enhanced
      by the presence of associated mapping criteria, particularly an isolated mid
      diastolic potential that cannot be dissociated from the tachycardia.

PMID- 8994436
TI  - Adhesion molecule P-selectin and vascular cell adhesion molecule-1 in enhanced
      heart allograft arteriosclerosis in the rat.
AB  - BACKGROUND: The increase of P-selectin on endothelial cells (EC) overlying human
      atherosclerotic plaques in classic atherosclerosis was recently established. We
      have previously shown that vascular cell adhesion molecule-1 (VCAM-1) is
      extensively expressed on EC of occluded arteries during accelerated transplant
      arteriosclerosis. In the present study, with the use of rat heart allografts
      under different doses of cyclosporine A (CsA), we investigated whether the
      expression of P-selectin is increased during chronic rejection and possibly
      coexpressed with VCAM-1 on EC. METHODS AND RESULTS: Rat cardiac allografts from
      DA donors to WF recipients were used. Without immunosuppression, these allografts
      show an irreversible rejection 7 days after transplantation. In the acute
      rejection model, syngeneic and allogeneic grafts were harvested 5 days after
      transplantation. In the chronic rejection model, allograft recipients received
      triple-drug immunosuppression, including azathioprine, methylprednisolone, and
      CsA in different doses. The grafts were removed 3 months after transplantation.
      During acute rejection, a significant expression of P-selectin (P < .01) and VCAM
      1 (P < .05) on microvascular endothelia, but not on arteries, was noticed. During
      intense chronic rejection (5 mg/kg CsA), arterial EC expressed P-selectin (P <
      .01) and VCAM-1 (P < .05) extensively. The expression of tumor necrosis factor
      alpha, a cytokine inducing both P-selectin and VCAM-1 expression, was upregulated
      in vascular medial cells (P < .05), in intimal cells (P < .01), and in
      interstitial mononuclear cells (P < .05). Linear regression analysis revealed a
      significant correlation between arterial P-selectin (P < .01) and VCAM-1 (P <
      .01) expression and the intensity of intimal thickening. Also, a significant
      correlation and coexpression of P-selectin and VCAM-1 in epicardial arteries was
      demonstrated (P < .05). CONCLUSIONS: The early expression of P-selectin on
      microvascular EC during acute rejection may be the basis of cell adhesion and
      infiltration into the site of inflammation. During chronic rejection, the
      intensity of arterial intimal thickening was significantly correlated with the
      intensity of P-selectin expression on EC, in addition to that of previously
      reported VCAM-1 expression. Thus, P-selectin may have a crucial role in the
      pathogenesis of chronic rejection in the vascular wall, augmenting the immune
      mediated injury against the allograft.

PMID- 8994437
TI  - Angiotensin II inhibits protein kinase A-dependent chloride conductance in heart
      via pertussis toxin-sensitive G proteins.
AB  - BACKGROUND: Angiotensin II receptors are reported to be abundant in the guinea
      pig ventricle; their coupling to adenylate cyclase in the heart, however, remains
      controversial. Therefore, we investigated the effect of angiotensin II on Cl-
      conductance activated by cAMP-dependent protein kinase. METHODS AND RESULTS:
      After minimizing the contribution of other ionic currents, exposure of single
      guinea pig ventricular cells to isoproterenol (40 to 50 nmol/L; 36 degrees C)
      elicited a typical protein kinase A-dependent Cl- conductance. Subsequent
      application of angiotensin II reduced the isoproterenol-induced conductance with
      an IC50 of 0.24 +/- 0.08 nmol/L. Angiotensin II also inhibited the Cl- currents,
      which were activated through stimulation of adenylate cyclase by forskolin and
      histamine receptors. CV-11974 (1 mumol/L), an antagonist selective for the
      angiotensin type 1 receptor, prevented the effect of angiotensin II. Angiotensin
      II did not inhibit the current that had been persistently activated by
      intracellular GTP gamma S (100 mumol/L), a nonhydrolyzable guanine nucleotide,
      plus isoproterenol. In addition, prior incubation of myocytes with pertussis
      toxin prevented the angiotensin II inhibitory action. Cl- conductance, when
      activated directly by intracellular dialysis with cAMP (1 mmol/L), was not
      affected by angiotensin II. Radioimmunologic measurement of cellular cAMP in the
      dissociated myocytes showed that angiotensin II inhibited the isoproterenol
      induced increase of cAMP. CONCLUSIONS: Angiotensin II receptors negatively couple
      to adenylate cyclase via pertussis toxin-sensitive G proteins, thereby inhibiting
      cardiac protein kinase A-dependent Cl- conductance.

PMID- 8994438
TI  - Evidence for altered balance between matrix metalloproteinases and their
      inhibitors in human aortic diseases.
AB  - BACKGROUND: Although abdominal aortic aneurysms (AAAs) exhibit increased
      expression of matrix metalloproteinases (MMPs), the functional balance between
      MMPs and their tissue inhibitors (TIMPs) remains uncertain. This report compares
      the proteolytic activity in normal aorta, aorto-occlusive disease (AOD), and AAA
      by use of a novel in situ zymographic technique. METHODS AND RESULTS: Infrarenal
      aortic specimens were obtained from 25 patients undergoing surgery for AOD or AAA
      and were compared with normal aortic tissue (n = 7) obtained from cadavers.
      Immunohistochemical staining was performed for collagenase (MMP-1), gelatinase A
      (MMP-2), stromelysin (MMP-3), TIMP-1, and TIMP-2. Net proteolytic activity was
      determined with in situ zymography whereby aortic sections were incubated on
      fluorescently labeled substrate. Proteolytic activity was detected under
      epifluorescent examination. Compared with normal aortic tissue, AOD and AAA
      tissue demonstrated marked increases in MMP-1 and MMP-3 immunoreactivity,
      predominantly in the neointima, and modest increases in TIMP-1. MMP-2 was
      increased in the diseased aortas, and TIMP-2 was abundant in normal, AOD, and AAA
      samples. Zymography revealed proteolytic activity in AOD and AAA tissues with
      active digestion of casein and gelatin substrate, particularly on the luminal
      portion of the specimens. Normal specimens exhibited no lytic activity.
      Comparison of AOD and AAA specimens revealed no difference in MMP/TIMP
      immunoreactivity or net proteolytic activity. CONCLUSIONS: MMP expression is
      markedly increased in AOD and AAA samples, and an imbalance between MMPs and
      their inhibitors results in similar proteolytic activity. The eventual formation
      of aneurysmal or occlusive lesions appears not to result from an ongoing
      difference in the proteolytic pattern.

PMID- 8994439
TI  - Protective role of nerve growth factor against postischemic dysfunction of
      sympathetic coronary innervation.
AB  - BACKGROUND: Nerve growth factor (NGF) is produced rapidly in myocardium after
      brief myocardial ischemia. It contributes to the maintenance of neural integrity
      in several tissues. We examined the effect of exogenous and endogenous NGF on
      ischemia-induced dysfunction of cardiac sympathetic nerves. METHODS AND RESULTS:
      In anesthetized dogs, bilateral stellate stimulation was performed, measuring
      changes in coronary vascular resistance (% delta CVR) before and after release of
      either a 7- or 15-minute occlusion of the left anterior descending coronary
      artery (LAD). NGF (10 ng.kg-1.min-1, n = 5) or vehicle (n = 6) was infused into
      the LAD in dogs during a 15-minute LAD occlusion. In separate experiments,
      antibody to NGF (anti-NGF, 2 ng.kg-1.min-1, n = 5) or vehicle (n = 6) was infused
      into dogs during a 7-minute LAD occlusion. After release of a 15-minute LAD
      occlusion, attenuation of the coronary constriction to stellate stimulation was
      seen in the vehicle group (30 +/- 3% to 15 +/- 1% increase in CVR, P < .05);
      however, no such reduction was seen in the group receiving NGF. A 7-minute LAD
      occlusion with reperfusion did not alter % delta CVR in the vehicle group (36 +/-
      6% versus 37 +/- 7%, P = NS) but attenuated % delta CVR in the anti-NGF group (39
      +/- 8% to 17 +/- 2%, P < .05). CONCLUSIONS: We conclude that exogenously infused
      and endogenously released NGF protects against postischemic neural stunning of
      sympathetic cardiac innervation.

PMID- 8994440
TI  - Endothelin-converting enzyme expression in the rat vascular injury model and
      human coronary atherosclerosis.
AB  - BACKGROUND: Endothelin 1 has been implicated in various human diseases, including
      atherosclerosis. In this study, we examined the expression and localization of
      endothelin-converting enzyme-1 (ECE-1), the final key enzyme of endothelin 1
      processing, in rat carotid arteries after balloon injury and in human coronary
      atherosclerotic lesions. METHODS AND RESULTS: ECE-1 mRNA levels and ECE activity
      in rat balloon-injured arteries started to increase between 2 and 5 days after
      injury. The endothelin 1 content of tissue in injured arteries was concomitantly
      increased. Immunohistochemical staining located ECE-1 signals in endothelial
      cells in uninjured arteries, whereas ECE-1 immunoreactivity was detected in
      neointimal smooth muscle cells in injured arteries 5 to 14 days after balloon
      denudation. The size of the neointima was effectively reduced by phosphoramidon,
      an inhibitor of neutral metalloproteases, including ECE-1. In human coronary
      atherosclerotic lesions, intense ECE-1 immunoreactivity was detected in subsets
      of cells embedded in atheromatous plaque that correspond to smooth muscle cells
      and macrophages, as identified by staining for smooth muscle alpha-actin and CD68
      surface marker, respectively. CONCLUSIONS: The present study ascertained that ECE
      1 is expressed in neointimal smooth muscle cells in rat balloon-injured arteries
      and in both smooth muscle cells and macrophages in human coronary atherosclerotic
      lesions. Blockade of ECE-1 was effective in reducing neointimal formation after
      balloon injury. Thus, ECE-1 may contribute to the process of injury-induced
      neointimal formation and atherosclerosis through the autocrine/paracrine effects
      of endothelin 1.

PMID- 8994441
TI  - Mechanisms of altered contractile responses to vasopressin and endothelin in
      canine coronary collateral arteries.
AB  - BACKGROUND: Mature coronary collateral arteries are hyperresponsive to
      vasopressin; in contrast, contractile responses of collaterals to endothelin are
      attenuated. Our goal was to determine the cellular mechanisms underlying these
      differences in reactivity using two sizes of canine collateral arteries isolated
      from hearts subjected to chronic coronary occlusion. METHODS AND RESULTS:
      Contractile responses to vasopressin (100 mmol/L) were enhanced threefold to
      fourfold in near-resistance (approximately 200 microns lumen diameter) and
      conduit (approximately 500 microns lumen diameter) collateral arteries compared
      with similarly sized noncollateral coronary arteries (P < .01). In contrast,
      contractions of both sizes of collaterals in response to endothelin (0.01 to 30
      nmol/L) were smaller than responses of size-matched noncollateral arteries (P <
      .05). Pretreatment with either indomethacin (5 mumol/L), a cyclooxygenase
      inhibitor, or NG-nitro-L-arginine methyl ester (100 mumol/L), a nitric oxide
      synthase inhibitor, did not alter the relative responsiveness of collateral
      arteries to vasopressin or endothelin compared with noncollateral arteries.
      Vasopressin produced greater increases of intracellular free Ca2+ (measured by
      use of fura-2 microfluorometry and Ca(2+)-dependent 42K+ efflux) in smooth muscle
      of collateral arteries than in smooth muscle of noncollateral arteries (P < .05).
      Surprisingly, endothelin-induced increases of Ca2+ were not different in smooth
      muscle of collateral and noncollateral arteries (P > .05). CONCLUSIONS: We
      conclude that altered contractile responsiveness of collateral arteries to
      vasopressin and endothelin does not result from altered synthesis/release of
      nitric oxide or prostaglandins. Parallel enhancement of vasopressin-mediated Ca2+
      and contractile responses suggests increases in vasopressin receptor number,
      affinity, and/or efficiency of coupling mechanisms in collateral smooth muscle.
      The dissociation between endothelin-induced contractile and Ca2+ responses of
      collaterals indicates that the mechanisms involved in increasing Ca2+ sensitivity
      of contractile proteins during endothelin stimulation may be altered in
      collateral arteries.

PMID- 8994442
TI  - Vascular endothelin-1 gene expression and effect on blood pressure of chronic ETA
      endothelin receptor antagonism after nitric oxide synthase inhibition with L-NAME
      in normal rats.
AB  - BACKGROUND: Vascular expression of the endothelin-1 gene may be associated with
      severe vascular hypertrophy. Because in rats, inhibition of NO synthase with the
      L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) induces blood
      pressure elevation associated with little cardiovascular hypertrophy, we studied
      vascular endothelin-1 gene expression in L-NAME-treated rats and the effects of
      chronic endothelin antagonism. METHODS AND RESULTS: Sprague-Dawley rats received
      100 mg.kg-1.d-1 L-NAME in their drinking water for 3 weeks. Systolic blood
      pressure rose to 189 +/- 3 mm Hg (P < .001 versus control rats). By Northern blot
      analysis, endothelin-1 mRNA levels were similar in aortas and mesenteric arteries
      of control and L-NAME-treated rats. The blood pressure of L-NAME hypertensive
      rats treated with the ETA-selective endothelin receptor antagonist A-127722 for 3
      weeks at a low dose (10 mg.kg-1.d-1) and a high dose (30 mg.kg-1.d-1) was not
      different from that of rats receiving L-NAME but not the endothelin antagonist.
      Treatment with the ACE inhibitor cilazapril lowered the blood pressure of L-NAME
      treated rats equally whether or not they were receiving the ETA antagonist.
      CONCLUSIONS: These results indicate that the endothelin system does not
      participate to an important degree in the mechanisms leading to elevated blood
      pressure after chronic NO synthase inhibition with L-NAME in normal rats. In the
      chronic model of L-NAME-induced hypertension, blockade of the renin-angiotensin
      system does not unmask an endothelin-dependent vasopressor tone. In addition,
      either NO does not regulate vascular endothelin-1 gene expression or L-NAME
      exerts an inhibitory effect on endothelin expression in blood vessels.

PMID- 8994444
TI  - Sex differences in coronary heart disease. Why are women so superior? The 1995
      Ancel Keys Lecture.

PMID- 8994443
TI  - Beneficial effects of amlodipine in a murine model of congestive heart failure
      induced by viral myocarditis. A possible mechanism through inhibition of nitric
      oxide production.
AB  - BACKGROUND: Although calcium channel blockers have not been shown to be
      beneficial for the treatment of patients with heart failure, a recent clinical
      trial demonstrated a favorable effect of amlodipine on the survival of patients
      with heart failure resulting from nonischemic dilated cardiomyopathy. We
      investigated the effects of amlodipine on a murine model of congestive heart
      failure induced by the M variant of encephalomyocarditis virus (EMCV). METHODS
      AND RESULTS: Four-week-old male DBA/2 mice were inoculated with EMCV and
      administered amlodipine, diltiazem, or vehicle PO for 2 weeks. The heart weight
      to-body weight ratio and the histopathological grades of myocardial lesions were
      significantly lower and survival was significantly increased in the amlodipine
      treated group (P < .01, P < .05, and P < .05, respectively) than in the control
      group. In vitro, amlodipine added to murine J774A.1 macrophages concomitant with
      EMCV inhibited nitrite formation in a concentration-dependent manner, but
      diltiazem did not. Furthermore, NG-monomethyl-L-arginine, an inhibitor of NO
      synthesis, decreased myocardial lesions significantly in this murine model.
      Immunohistochemistry revealed that the number of cells stained with antibody
      against an inducible NO synthase decreased significantly in the amlodipine
      treated group compared with that in the control group (P < .01). CONCLUSIONS:
      Amlodipine appears to have a protective effect against myocardial injury in this
      animal model of congestive heart failure. The therapeutic effect of amlodipine
      may be in part resulting from inhibition of overproduction of NO.

PMID- 8994445
TI  - Survivors of out-of-hospital cardiac arrest with apparently normal heart. Need
      for definition and standardized clinical evaluation. Consensus Statement of the
      Joint Steering Committees of the Unexplained Cardiac Arrest Registry of Europe
      and of the Idiopathic Ventricular Fibrillation Registry of the United States.
AB  - BACKGROUND: A wide variety of structural abnormalities are associated with the
      vast majority of cardiac arrests. However, there is no evidence of structural
      heart disease in approximately 5% of victims of sudden death, indicating that
      cardiac arrest in the absence of organic heart disease is more common than
      previously recognized. The risk of recurrence and the acute and long-term
      response to therapy are important but unanswered questions. Data from the small
      series reported so far are of limited value because of the lack of uniform
      criteria to define and diagnose idiopathic ventricular fibrillation (IVF).
      METHODS AND RESULTS: This report originates from a Consensus Conference convened
      by the Steering Committees of the European (UCARE) and North American (IVF-US)
      Registries on IVF under the auspices of the Working Group on Arrhythmias of the
      European Society of Cardiology. Its objective is to provide a unified definition
      of IVF and to outline the investigations necessary to make this diagnosis.
      Minimal diagnostic tests for the exclusion of an underlying structural heart
      disease include non-invasive (blood biochemistry, physical examination and
      clinical history, ECG, exercise stress test, 24-hour Holter recording, and
      echocardiogram) and invasive (coronary angiography, right and left ventricular
      cineangiography, and electrophysiological study) examinations. Programmed
      electrical stimulation, ventricular biopsy, and ergonovine test during coronary
      angiography are recommended but not mandatory. CONCLUSIONS: It is recognized that
      despite careful evaluation, conditions such as focal cardiomyopathy, myocarditis,
      or fibrosis and transient electrolyte abnormalities may remain silent. Therefore,
      patients should undergo careful follow-up, with noninvasive tests repeated every
      year. The existence of a unified terminology will allow meaningful comparison of
      data collected by different investigators and will thus contribute to a better
      understanding of IVF.

PMID- 8994446
TI  - Images in cardiovascular medicine. Single atrium.

PMID- 8994447
TI  - Media reports about a consumer guide to coronary artery bypass graft surgery.

PMID- 8994448
TI  - 1,3 Butadiene and environmental tobacco smoke.

PMID- 8994449
TI  - Comments on "Special report: recommendations for safe current limits for
      electrocardiographs'.

PMID- 8994450
TI  - Abnormal myocardial development.

PMID- 8994451
TI  - Atherosclerotic arterial remodeling in the superficial femoral artery: individual
      variation in local compensatory enlargement response.

PMID- 8994453
TI  - Ischemic stroke and the gene for angiotensin-converting enzyme in Japanese
      hypertensives.

PMID- 8994452
TI  - Heart rate variability standards.

PMID- 8994454
TI  - Increasing socioeconomic inequalities and the mental health of the poor.

PMID- 8994455
TI  - Long-term outcome of panic disorder treatment. A review of the literature.
AB  - This review was designed to provide a detailed analysis of long-term outcome data
      from treatment studies for panic disorder, with the goal of ascertaining
      differential efficacy of the available treatments. Studies were included if they
      were published after 1980 and if follow-up took place at least 6 months after
      treatment termination. Thirty-one studies were located. A variety of
      methodological problems were found in these studies, including lack of clarity of
      diagnosis, lack of clarity in the treatment administered, and inadequately
      tracked nonstudy treatments during the study and follow-up periods, which limited
      the information that could be obtained about long-term outcome. Long-term outcome
      studies that closely track the additional treatments that patients receive are
      necessary to draw more definitive conclusions about differential treatment
      efficacy for panic disorder. Available data suggest that there is limited
      evidence for long-term maintenance of short-term treatment gains in panic
      disorder patients in the absence of continued treatment.

PMID- 8994457
TI  - Possible selves in major depression.
AB  - Ratings of possible selves and resultant self-concept discrepancies were examined
      in 25 patients diagnosed with major depression and 25 control subjects. Self
      concept discrepancies significantly discriminated patients from controls. The
      presence of negative features in the self-schema was a stronger indicator of
      depressive symptomatology than was the absence of positive self-appraisal.
      Depressives' future projections of self were less pessimistic than predicted by
      cognitive theories of depression.

PMID- 8994456
TI  - A 2-year follow-up of social phobia. Status after a brief medication trial.
AB  - Although social phobia is thought to be a chronic disorder, little is known about
      its long-term course in patients who engage in brief treatment studies. We,
      therefore, conducted a follow-up study of social phobics who had participated in
      a brief, placebo-controlled treatment trial of clonazepam. Of the original 75
      subjects, 56 were assessed through telephone interview and self-report
      questionnaires that evaluated current social phobia symptoms. Information was
      also gathered about treatment received in the 2-year interval since the initial
      pharmacotherapy trial. The group as a whole showed maintenance of the gains
      acquired during initial treatment. On a number of symptom scales, subjects
      initially treated with clonazepam exhibited significantly less severe scores
      compared with placebo subjects. This study provides evidence of long-term benefit
      for social phobics when treated with a brief medication trial.

PMID- 8994458
TI  - Self-reported aggressive behavior in patients with stroke.
AB  - This study represents a first attempt to identify some of the clinical and
      pathoanatomical correlates of violent outbursts in patients with cerebrovascular
      accident. Subjects were selected from a population of patients hospitalized with
      acute stroke. Although we did not have behavioral measures of violent behavior,
      patients who reported having had violent outbursts were identified based on
      clinical ratings on a structured interview. Subjects were asked if they had
      experienced episodes of anger accompanied by behaviors ranging from shouting to
      violence during the time since their stroke. These patients were compared with
      controls matched for demographic variables. Violent patients had higher total
      Present State Exam and Hamilton-D scores. The percentage of patients with
      cognitive impairment in the angry outburst group (66%) was greater than the
      control group (22%). Outburst patients had a higher frequency of left-hemisphere
      lesions (46.7%) compared with controls (29.4%). When lesion volumes were
      statistically equated, proximity of lesion to the frontal pole was one of the
      factors related to the self-reported irritable/violent behavior. To determine
      whether depression explained our findings, we carried out two-way analyses of
      variance with angry outburst and major depression group membership as factors.
      Effects of left anterior lesion location and cognitive impairment on violence
      remained present. These findings suggest that the potential for anger and
      violence in patients with stroke has multiple clinical and neuropathological
      correlates, including greater cognitive impairment and left anterior hemisphere
      lesions.

PMID- 8994459
TI  - Gender differences in personality disorders in psychiatrically hospitalized young
      adults.
AB  - We examined gender differences in DSM-III-R personality disorders in
      psychiatrically hospitalized young adults. Structured diagnostic interviews were
      reliably performed on a consecutive series of 118 inpatients. Men were
      significantly more likely to meet criteria for cluster A, schizotypal, and
      antisocial personality disorders. To reduce variability due to axis I
      heterogeneity, we retested for gender differences in a subgroup of patients with
      major depression. Depressed men were more likely to meet criteria for cluster A,
      schizotypal, and cluster C personality disorders. Women were not observed to have
      a higher frequency of any personality disorder than men in either study group.

PMID- 8994460
TI  - Does right parietal cortex and vestibular dysfunction underlie body image
      distortion?

PMID- 8994461
TI  - Striking back at stroke.

PMID- 8994462
TI  - Chemosensory and somatosensory regeneration after lingual nerve repair in humans.
AB  - PURPOSE: The objective of these studies was to measure the impact of Class IV and
      V lingual nerve injuries on taste sensitivity and taste receptor density of the
      anterior tongue before and after microneurosurgical repair. MATERIALS AND
      METHODS: Citric acid detection threshold and suprathreshold magnitude response
      were measured on the anterior tongue in 12 adult volunteers with unilateral
      lingual nerve Class IV or V injuries. The right and left sides of the anterior
      tongue were tested at each session to assess the effect of nerve damage before
      and 1, 3, 6, and 12 months after repair. Whole-mouth threshold and suprathreshold
      scales of citric acid taste intensity were measured. The level of sensory
      impairment was scaled at each test session using a clinical neurosensory test
      algorithm. Finally, patients completed an 11-item instrument survey that queried
      the patient's perceived expectations of surgery on sensory, taste, and general
      health before surgery and the patient's perceived outcome of surgery at each
      postrepair session. The patient's perceived global satisfaction of surgery was
      also assessed. RESULTS: All 12 patients failed to detect and scale citric acid
      and had complete or severe sensory impairment on the injured side of the anterior
      tongue. One year after repair, 50% of the patients demonstrated a substantial
      increase in the number of fungiform papillae, pores, and ratio of pores/papilla
      at the same time as they demonstrated the ability to detect and scale citric
      acid. After repair, patients perceived the greatest improvements in the
      categories of eating, chewing, feeling, and taste, and the least in speech.
      CONCLUSION: Lingual nerve repair may result in significant changes in
      somatosensory and chemosensory function and taste bud anatomy on the anterior
      tongue over time.

PMID- 8994463
TI  - Bone level changes in patients with transmandibular implants.
AB  - PURPOSE: In this article, the mandibular bone height in edentulous patients
      previously treated with a transmandibular implant was evaluated after the
      dentures were modified according to the latest prosthetic protocol. PATIENTS AND
      METHODS: The bone height of 36 patients was measured on three radiographs; the
      first at the time of insertion of the implant, the second just before using the
      latest prosthetic protocol, and the third 1 year later. RESULTS: A slight bone
      increase at the lateral posts and at the cortical screws mesial to these posts
      was measured. No significant bone increase was found above the lateral cortical
      screw. CONCLUSION: The bone increase that is found in this study was not of the
      extent indicated in earlier reports.

PMID- 8994464
TI  - Interleukin 1 beta and stromelysin (MMP3) activity of synovial fluid as possible
      markers of osteoarthritis in the temporomandibular joint.
AB  - PURPOSE: This study investigated the early signs of synovitis and cartilage
      degradation by means of synovial fluid analysis in temporomandibular joints
      (TMJs) with internal derangement (closed lock) or osteoarthritis (OA). PATIENTS
      AND METHODS: Synovial fluid was obtained from 25 TMJs in 22 patients diagnosed
      with closed lock and from 15 asymptomatic TMJs of 12 normal controls. IL-1 beta
      concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and
      proteinase activity was detected by means of gelatin enzymography. RESULTS: Nine
      of the 25 TMJs with closed lock (CL group) exhibited osteolytic changes on the
      surface of the condyle. TMJs in the normal control group did not show any bony
      changes. Mean IL-1 beta concentration in the synovial fluid (SF) protein in the
      CL group was 330.1 +/- 347.7 pg per 100 micrograms protein, which was
      significantly higher than in the normal control (76.7 +/- 95.3 pg/100 micrograms
      SF-protein). Synovial fluid from the TMJs with osteolytic changes contained
      higher levels of IL-1 beta (531.8 +/- 379.6 pg/100 micrograms SF-protein) than
      those without bony changes (216.7 +/- 280.1 pg/100 micrograms SF-protein). Matrix
      metalloproteinase (MMP) activity with a molecular weight of 50 kd (stromelysin or
      MMP3) was detected in a highly augmented form in two synovial fluid samples of
      seven closed lock patients. CONCLUSION: The results suggest that IL-1 beta levels
      in synovial fluid of the TMJ have a positive correlation with OA change. The MMP3
      activity detected was greatly increased in patients with cartilage degradation.
      These findings suggest that both changes may be important markers of early bone
      deterioration in TMJs that are undetectable by radiograph imaging.

PMID- 8994465
TI  - The accuracy of clinical examination versus frozen section in the diagnosis of
      parotid masses.
AB  - PURPOSE: This study evaluated the role of clinical examination and frozen
      sections in the diagnosis and management of parotid masses. PATIENTS AND METHODS:
      One hundred seventy patients underwent parotidectomy. Of these, the data on 65
      were analyzed, with emphasis on accuracy of the clinical diagnosis and frozen
      section results compared with the final histologic diagnosis. RESULTS: The
      results showed that the sensitivity of frozen sections for malignancy was 93.3%,
      and the specificity for a benign tumor was 95.74%, with a 4.2% false-negative
      rate and a 6.7% false-positive rate. Of the 65 patients, 58 patients had an
      explicit clinical diagnosis; 88.4% were correctly identified as benign tumors,
      and 78.6% were correctly diagnosed as malignancies. The false-positive and false
      negative rates were 21.4% and 7.0%, respectively. CONCLUSIONS: The results of
      this study suggest that clinical examination can provide information that is not
      very reliable, and the surgical plan should be based on intraoperative frozen
      sections rather than the history and clinical features.

PMID- 8994466
TI  - A comparison of patient-controlled and fixed schedule analgesia after
      orthognathic surgery.
AB  - PURPOSE: The purpose of this prospective study was to compare the effectiveness
      of patient-controlled intravenous (i.v.) opioid analgesic administration (PCA)
      with fixed schedule and dosage oral/rectal administration of naproxen, and opioid
      analgesics intramuscularly/orally as needed (i.m./p.o. prn) for postoperative
      analgesia over a period of 48 to 56 hours after surgery. PATIENTS AND METHODS:
      There were 75 orthognathic patients aged 25.73 +/- 8.01 years, subdivided into
      three study groups of 25: codeine group (8 males, 17 females); naproxen group (5
      males, 20 females) and PCA group (8 male, 17 females). The degree of analgesia
      was assessed every 4 hours from 8:00 AM to 8:00 PM hours on days 1 and 2
      postsurgery using a visual analog scale (VAS). Mean daily and mean overall VAS
      scores were treated as parametric data and were analyzed accordingly. Mean daily
      VAS scores also were categorized as comfort days when mean scores were less than
      3.0 cm, and as discomfort days when mean scores were equal to or greater than 3.0
      cm. ANOVA were used to analyze patient demographics, pain scores, surgical time,
      fentanyl used during general anaesthesia, analgesic morphine equivalents, and
      vital signs. Chi-square tests were used to analyze sex, comfort (discomfort)
      days, and nausea and vomiting. Mean VAS ratings were analyzed using independent t
      tests. RESULTS: The three groups were matched in demographics, surgical time,
      fentanyl used, and sex. The PCA group used less than half the amount of morphine
      equivalent as the codeine group (P = .0001). Both the naproxen and the PCA groups
      were significantly more comfortable than the codeine group during day 1 and day 2
      postsurgery. The codeine group had significantly more episodes of nausea than
      either the naproxen or the PCA groups. CONCLUSION: In patients undergoing
      orthognathic surgery, the naproxen and PCA regimens provided better analgesia
      than the codeine regimen.

PMID- 8994467
TI  - Functional and morphologic alterations after anterior or inferior repositioning
      of the maxilla.
AB  - PURPOSE: The purpose of this investigation was 1) to compare functional and
      morphologic measurements between controls and patients scheduled for anterior or
      inferior repositioning of the maxilla, and 2) to examine how these patients' oral
      function adapted after surgery. PATIENTS AND METHODS: Nine male patients
      undergoing anterior and/or inferior repositioning of the maxilla were compared
      with 26 male controls preoperatively and up to 3 years after surgery. Measures of
      skeletal morphology, mandibular range of motion, maximum voluntary bite force,
      and levels of electromyographic (EMG) activity in the anterior and posterior
      temporalis and masseter muscles during isometric bites were made on all subjects
      over time. One-way ANOVA was used to compare the controls, the patients before
      surgery, and the patients after surgery. RESULTS: Before surgery, most of the
      patients had morphologic characteristics of mandibular prognathism and maxillary
      retrognathism. Surgery made the patients' skeletal morphology similar to controls
      except for mandibular length, upper facial height, and palatal plane angle, which
      were significantly greater than those of controls. There were no significant
      differences in jaw muscle mechanical advantage between controls and patients
      either before or after surgery. Hypomobility of the jaw was apparent at 6 weeks
      and 6 months after surgery, but returned to normal values within 1 to 2 years.
      Before surgery, the patients had maximum voluntary bite forces significantly less
      than those of controls. Bite forces in patients steadily increased after surgery,
      approaching significantly higher values than those of controls. Before surgery,
      patients' muscle activity levels per unit of bite force were not significantly
      different from those of controls. Most of the patients' muscle activity levels
      per unit of bite forces at all bite positions showed no significant change after
      surgery. CONCLUSIONS: The results of this study suggest that anterior or inferior
      repositioning of maxilla produces some significant functional benefits in
      patients.

PMID- 8994468
TI  - Maxillary perfusion during Le Fort I osteotomy after ligation of the descending
      palatine artery.
AB  - PURPOSE: Controversy exists regarding management of the descending palatine
      artery (DPA) during Le Fort I osteotomy. Some surgeons advocate preserving the
      DPA, and others ligate the vessels. The purpose of this study was to evaluate
      maxillary gingival blood flow (GBF) during Le Fort I osteotomy in a sample of
      patients with and without ligation of the DPA. PATIENTS AND METHODS: Using a
      prospective randomized clinical study, we enrolled a study sample composed of 34
      patients undergoing Le Fort I osteotomy. The patients were randomly assigned to
      either study group 1 (16) (DPA ligated) or group 2 (18) (DPA preserved). To
      measure maxillary GBF during the operation, we used laser Doppler flowmetry
      (LDF). The predictor variable was status of DPA management (ligated or
      preserved). The outcome variable was change in GBF over time. RESULTS: (DPA).
      Before ligation (or simulated ligation) of the DPA, the mean GBF for groups 1 and
      2 was 11.4 +/- 8.6 and 11.9 +/- 9.4 mL/min/100 g tissue, respectively (P = .88).
      After ligation of the DPA in group 1, the mean GBF was 10.0 +/- 7.7 mL/min/100 g
      tissue. At the corresponding time in group 2 (DPA preserved), the mean GBF was
      12.6 +/- 9.4 mL/min/100 g tissue. The difference in mean GBF between groups 1 and
      2 was not statistically significant (P = .43). CONCLUSION: There were no
      statistically significant differences in mean maxillary GBF between patients
      having the DPA ligated and those having the DPA preserved as measured using LDF
      during Le Fort I osteotomy.

PMID- 8994469
TI  - Extracellular alkaline phosphatase activity as a possible marker for wound
      healing: a preliminary report.
AB  - PURPOSE: This study evaluated the use of extracellular alkaline phosphatase
      activity as a marker of wound healing. MATERIALS AND METHODS: Fifteen 8-week-old
      Wistar rats, weighing 180 to 220 g and of both sexes, made up the material of
      this study. Histopathologic aspects of the healing of full-thickness of wounds
      created on the dorsal skin of these rats were studied by means of alkaline
      phosphatase (ALP) enzyme histochemistry and routine microscopy. RESULTS: The
      current study showed an exclusive localization of extracellular ALP activity in
      the regions of granulation tissue formation. This localization was time related,
      and decreased as healing progressed. CONCLUSIONS: Although the biologic
      significance of ALP is still obscure, use of extracellular ALP activity as a
      simple and reliable histochemical process marker of the skin wound healing is
      proposed.

PMID- 8994471
TI  - Dermatography for the treatment of telangiectasis after radiation therapy in the
      head and neck: report of cases.

PMID- 8994470
TI  - The case for mandibular condylotomy in the treatment of the painful, deranged
      temporomandibular joint.

PMID- 8994472
TI  - Carotid aneurysm: a rare cause of cervical swelling.

PMID- 8994473
TI  - Treatment of central arteriovenous malformation of the mandible via resection and
      immediate replantation of the segment: a case report.

PMID- 8994474
TI  - Malignant fibrous histiocytoma after radiation for ameloblastoma of the maxilla.

PMID- 8994475
TI  - Ascher syndrome: report of two cases.

PMID- 8994476
TI  - Life-threatening, delayed hemorrhage after Le Fort I osteotomy requiring surgical
      intervention: report of two cases.

PMID- 8994477
TI  - Maxillofacial spear gun accident: report of two cases.

PMID- 8994478
TI  - Osteomyelitis of the mandible in a patient with acquired systemic analgia.

PMID- 8994479
TI  - Salvage technique for a severed endotracheal cuff pilot tube.

PMID- 8994480
TI  - Sleep disturbance, psychosocial correlates, and cardiovascular disease in 5201
      older adults: the Cardiovascular Health Study.
AB  - OBJECTIVES: To describe the prevalence of self reported sleep disturbances in
      older men and women and to describe their relationships with health status and
      cardiovascular disease (CVD). DESIGN: Cross-sectional study of sleep disturbance,
      CVD, general health, psychosocial factors, physical function, and use of
      psychotropic medications. SETTING: Participants of the Cardiovascular Health
      Study, 5201 adults aged 65 and older recruited from a random sample of
      noninstitutionalized Medicare enrollees in four US communities. MEASURES: Self
      reported sleep disturbances and standardized questionnaires for cardiopulmonary
      symptoms and diseases, depression, social support, activities of daily living,
      physical activity, cognitive function, and current medications, spirometry, ECG,
      echocardiography, and carotid ultrasound. RESULTS: Women were twice as likely as
      men to report difficulty falling asleep (30% vs 14%). Daytime sleepiness,
      difficulty falling asleep, and frequent awakenings increased in prevalence with
      age. All symptoms were related strongly to depression. Symptoms of daytime
      sleepiness were also related strongly to poor health and limitations in
      activities of daily living in men and women. In multivariate analysis, men taking
      benzodiazepines were likely to report difficulty falling asleep and daytime
      sleepiness, whereas women taking benzodiazepines reported difficulty falling
      asleep and waking up too early. After accounting for these factors, the only
      cardiovascular disease independently associated with sleep disturbances was
      angina. Men and women with confirmed angina were 1.6 times more likely to report
      trouble falling asleep. Independent relationships between sleep disturbances and
      cardiovascular risk factors such as obesity, hypertension, smoking, and diabetes
      were relatively weak and inconsistent, though smokers were less likely to report
      frequent awakenings. CONCLUSIONS: Sleep disturbances are relatively common in
      older men and women and are associated with poor health, depression, angina,
      limitations in activities of daily living, and the use of benzodiazepines.

PMID- 8994481
TI  - Effect of pharmacologic lipid lowering on health-related quality of life in older
      persons: results from the Cholesterol Reduction in Seniors Program (CRISP) Pilot
      Study.
AB  - OBJECTIVE: To determine the effect of lovastatin therapy on health-related
      quality of life in older persons. DESIGN: A prospective, randomized, double blind
      clinical trial. SETTING: Four university medical center research clinics.
      PARTICIPANTS: There were 431 men and women, primarily 65 years of age or older,
      with low density lipoprotein levels greater than 159 mg/dL and less than 221
      mg/dL. Exclusion criteria included a Mini-Mental state score less than 24 or
      presence of recent cardiovascular events or other serious chronic disease likely
      to shorten survival. INTERVENTION: All participants were administered the
      National Cholesterol Education Program step one diet and were then randomized to
      placebo, 20 mg lovastatin, or 40 mg lovastatin. MEASUREMENTS: Areas of health
      related quality of life assessed in the Cholesterol Reduction in Seniors Program
      (CRISP) included: (1) physical functioning, (2) sleep behavior, (3) social
      support, (4) depression, (5) cognitive function, and (6) health perception. Three
      global change questions asked the patients to judge change in general health
      since starting the study diet or the study medication and change in ability to
      function or care for self. Although some patients were followed for a total of 12
      months, all participants were followed for 6 months, and 6-month data have been
      used for the primary analysis in this paper. RESULTS: Patients treated with 20 mg
      of lovastatin had a 17% and 24% reduction in total cholesterol and LDL
      cholesterol, respectively. Patients treated with the 40-mg lovastatin dose
      achieved reductions of 20% for total cholesterol and 28% for LDL-cholesterol.
      Complaints of possible adverse events were remarkably similar in the two active
      treatment groups and the placebo group. At 6 months of follow-up there were no
      statistically significant differences found in mean change scores from baseline
      between treatment groups on the health-related quality of life measures (physical
      functioning, sleep, social support, depression, cognitive function scales, health
      perception) or global questions. CONCLUSIONS: This study demonstrates that
      lovastatin was extremely well tolerated in an older cohort, both with regard to
      symptoms and to health-related quality of life.

PMID- 8994483
TI  - Postural balance and self-reported functional ability in 75-year-old men and
      women: a cross-national comparative study.
AB  - OBJECTIVE: To study postural balance in relation to self-reported functional
      ability (mobility and ADL) and general physical activity in elderly men and women
      living in three different Nordic environments. PARTICIPANTS: A random sample of
      448 men and 556 women from among the 75-year-old residents in Glostrup, Denmark,
      and Goteborg, Sweden, and all the residents of relevant age (127 men and 261
      women) in Jyvaskyla, Finland. MEASUREMENTS: Assessment of postural balance with
      eyes open and closed using a piezoelectric force platform. A structured interview
      on self-reported functional ability and physical activity. An in-laboratory
      medical examination. RESULTS: In spite of some differences in balance between the
      groups studied (better results in women compared with men and, to some extent,
      better results in the participants from Denmark and Finland than in those from
      Sweden), the performance in the balance tests was similarly associated with
      functional ability within all groups. The subjects reporting no need of help in
      performing the ADL and mobility functions performed significantly better in the
      balance tests. These differences were seen more clearly in the control of
      anteroposterior movement of center of forces than in the mediolateral direction.
      The performance in the balance tests was also significantly better among the
      subjects reporting a higher level of general physical activity than in their less
      active counterparts. Physical activity and than in their less active
      counterparts. Physical activity and certain long standing illnesses modified
      significantly the relationship between postural balance and ADL-performance. When
      these factors were analyzed simultaneously, the role of balance as a predictor of
      ADL-performance largely disappeared. CONCLUSIONS: The results suggest that good
      balance is one of the prerequisites of performance without difficulty in mobility
      and ADL functions. Physical exercise may help to maintain balancing abilities in
      old age; good balance, in turn, may also enable a physically active way of life.
      The associations of balance with functional ability and physical activity were
      independent of sex and locality. The results also support the validity of static
      stabilometry as a tool for evaluating threats to functional limitations in older
      subjects.

PMID- 8994482
TI  - HM-PAO (CERETEC) SPECT brain scanning in the diagnosis of Alzheimer's disease.
AB  - OBJECTIVE: To evaluate the accuracy of Single Photon Emission Computed Tomography
      (SPECT) scanning in the diagnosis of Alzheimer's Disease (AD) and its capacity to
      improve the diagnostic accuracy of conventional clinical evaluation. DESIGN:
      Comparison of SPECT scanning of AD and normal subjects with the criterion
      standard of clinical diagnosis confirmed by 1-year repeated evaluation. SETTING:
      A memory clinic in a tertiary care university hospital. PATIENTS: One hundred
      twenty patients were evaluated upon entering the Jewish General Hospital (McGill
      University) Memory Clinic. Fifty-eight patients were diagnosed as having AD and
      17 as having vascular dementia. Twenty unmatched controls (recruited mainly
      through newspaper advertisements) were normal, and 25 had cognitive impairment
      without dementia (not included in the statistical analysis). MAIN OUTCOME
      MEASURES: Comparison of visual inspection of SPECT, based on the system of
      classification developed by Holman et al., using B pattern alone as positive or B
      (bilateral posterior temporal and/or parietal cortex deficits) or C (bilateral
      posterior temporal and/or parietal deficits with additional defects) pattern and
      B or C or D (unilateral posterior temporal and/or parietal defects with or
      without additional defects) as positive compared with clinical diagnosis after
      repeated evaluations. Sensitivity and specificity, as well as positive predictive
      value (PPV) and negative predictive value (NPV) based on the prevalence of AD in
      a memory clinic setting of 30% or 50%, were calculated. RESULTS: With B pattern
      as positive, the sensitivity of SPECT was 21% whereas the specificity was 80%.
      With B or C as positive, the sensitivity was 29% and the specificity was 75%.
      With B or C or D as positive, the sensitivity was 55% and the specificity was
      65%. With a 30% prevalence, the PPV with B pattern as positive was 31% whereas
      the NPV was 30%. The PPV with B or C as positive was 33% while the NPV was 29%,
      and the PPV with B or C or D as positive was 40% whereas the NPV was 23%. With a
      50% prevalence, the PPV with B pattern as positive was 51% and the NPV 49.6%; the
      PPV with B or C as positive was 54% and the NPV 48.6%; the PPV with B or C or D
      as positive was 61% while NPV was 41%. CONCLUSION: The sensitivity and
      specificity were too low for SPECT to be useful as a diagnostic test for AD. The
      poor positive and negative predictive values in our tertiary care clinic mean
      that SPECT is not useful in "ruling-in" or "ruling-out" AD in that setting. In
      fact, clinical evaluation is more accurate.

PMID- 8994484
TI  - Predictors of pressure ulcer healing among long-term care residents.
AB  - OBJECTIVES: To identify predictors of pressure ulcer healing among long-term care
      residents. DESIGN: A retrospective cohort study. SETTING: Department of Veterans
      Affairs (VA) long-term care facilities. PARTICIPANTS: All long-term care
      residents with a pressure ulcer on April 1, 1993, who remained institutionalized
      as of October 1, 1993. Patients and pressure ulcer status were identified from
      the Patient Assessment File, a VA administrative database. MEASUREMENTS: Pressure
      ulcers were considered healed if patients were without an ulcer on October 1,
      1993. Predictors of pressure ulcer healing were selected from among patient
      characteristics in the Patient Assessment File. RESULTS: Pressure ulcers were
      present in 7.7% of the long-term care residents institutionalized as of April 1,
      1993. Among the 819 pressure ulcer patients remaining institutionalized as of
      October 1, 1993, ulcers had healed in 442 (54.0%). Seventy-two percent of
      patients with Stage 2 ulcers were ulcer-free at 6 months, compared with 45.2% of
      patients with Stage 3 ulcers and 30.6% of those with Stage 4 ulcers (P < .001).
      Significant (P < .05) independent predictors of healing included pressure ulcer
      size (Odds ratio (OR) = 5.2 for Stage 2 ulcers, OR = 1.5 for Stage 3 ulcers),
      older age (OR = 1.5), and receiving rehabilitation services (OR = 1.3 for each
      additional type of therapy). Both immobility (OR = .3) and incontinence (OR = .7)
      were associated with ulcers not healing. CONCLUSIONS: Most Stage 2 pressure
      ulcers, and many larger ulcers encountered in long-term care settings will heal.
      Baseline patient characteristics are important predictors of healing.
      Interventions may then be targeted at patients whose ulcers are unlikely to heal,
      and observed facility performance may be compared with expected outcomes.

PMID- 8994485
TI  - Functional outcome of cognitively impaired hip fracture patients on a geriatric
      rehabilitation unit.
AB  - OBJECTIVES: To compare outcomes (physical functions and discharge destinations)
      of cognitively impaired and intact older hip fracture patients, and to identify
      cognitive skills related to functional gains. DESIGN: Prospective longitudinal
      study of hip fracture patients treated on an acute inpatient rehabilitation
      service, with evaluation of functional performance and living status determined
      at admission and discharge. SETTING: A specialized inpatient geriatric
      rehabilitation program at Wesley Woods Geriatric Hospital, which is affiliated
      with Emory University School of Medicine. SUBJECTS: Fifty-eight hip fracture
      patients, 35 with and 23 without cognitive impairment. MEASUREMENTS: Cognitive
      functioning measured by the Mattis Dementia Rating Scale (MDRS); functional
      outcome assessed by the Functional Independence Measure (FIM); comparison of pre
      fracture with discharge living environments. MAIN RESULTS: Both cognitively
      impaired and intact hip fracture patients exhibited similar overall FIM motor
      improvements as well as functional gains in specific FIM areas measuring self
      care, sphincter control, and locomotion (e.g., walking). Cognitively intact
      patients, however, displayed significantly greater gains in mobility (e.g.,
      transfers) at discharge. Cognitively impaired patients who lived in the community
      were as likely as intact patients to return to the community. Patients who
      entered the program at a modified dependence level (FIM 3-5) and achieved motor
      independence at discharge (FIM 6-7) had higher MDRS initiation/ perseveration and
      memory scores. CONCLUSIONS: Hip fracture patients with cognitive impairments can
      achieve positive outcomes as defined by functional improvement and discharge
      destination. Intensive post-fracture rehabilitation in the early phase of
      recovery may promote functional independence and a return to the community for
      older patients at risk for nursing home placement. Future research should examine
      the long-term maintenance of these improvements and explore how rehabilitation
      interventions can be altered to enhance outcome.

PMID- 8994487
TI  - A comparison of nursing home-acquired pneumonia patients with patients with
      community-acquired pneumonia and nursing home patients without pneumonia.
AB  - OBJECTIVES: To determine the factors responsible for mortality and
      characteristics unique to patients with nursing home acquired pneumonia (NHAP).
      DESIGN: A prospective study of 71 patients with NHAP, 79 patients admitted from
      nursing homes for conditions other than pneumonia (NP), and 93 patients with
      community-acquired pneumonia (CAP). SETTING: A teaching hospital that serves as
      the community hospital for the City of Halifax. RESULTS: The 32% in-hospital
      mortality rate for NHAP was higher than the 14% rate for CAP (P < .05) but not
      significantly higher than the 23% mortality rate for NP patients. The most
      important determinants for long-term (52 weeks) outcome were complications during
      hospital stay, odds ratio for mortality 3.55, and self sufficiency at time of
      admission, odds ratio for mortality 0.306. While bacteremia rates were similar at
      8% for NHAP, 13% for CAP, and 17% for NP, there was a trend toward a higher rate
      of pneumococcal bacteremia in the CAP group. CAP patients were more likely to
      receive ventilatory support, 13% versus 3% for NHAP and 4% for no pneumonia
      patients despite similar levels of hypoxemia in the two pneumonia groups.
      CONCLUSIONS: The in-hospital mortality rate for NHAP is higher than that for CAP.
      The 1-year survival rate is determined by self-sufficiency at time of admission
      and absence of complications during hospital stay and is not group (e.g., nursing
      home) dependent.

PMID- 8994486
TI  - Implementation of the Patient Self-Determination Act (PSDA) in nursing homes in
      New York City.
AB  - OBJECTIVE: To examine implementation of the Patient Self Determination Act
      (PSDA), verbal directives, procedures for determination of resident' decision
      making capacity, and role of ethics committees in nursing homes in New York City.
      DESIGN: Telephone survey. PARTICIPANTS: Social workers in 109 (69%) nursing homes
      in New York City. MEASUREMENT: An 80-item instrument addressing: (1) social
      worker knowledge of the PSDA; (2) informing residents about advance directives
      (living wills and durable power of attorney for health care [health care
      proxies]); (3) determination of decision-making capacity to be informed about
      advance directives; (4) estimates of advance directives executed; (5) perceptions
      of PSDA effect; (6) ethics committees; (7) follow-up and documentation; and (8)
      staff and community education. MAIN RESULTS: Virtually all social workers in
      nursing homes stated that they made what they perceived to be a "serious effort"
      to inform residents about advance directives and to have residents execute
      directives (preferentially a health care proxy). More residents were thought to
      have executed a directive pursuant to the PSDA law than before the Act went into
      effect. Social workers in most homes informed residents about directives through
      face-to-face discussions. Most homes, however, did not inform residents who were
      thought to lack decision-making capacity about their right to execute a
      directive. Only 37% of homes had written procedures to determine a resident's
      decision-making capacity to be informed about directives; most homes relied on
      physician and social work assessments. Voluntary homes differed significantly
      from proprietary homes in that they were larger, more likely to have an ethics
      committee, and more aggressive in their implementation of the PSDA. Forty-five
      percent of homes with an ethics committee had written procedures for
      determination of resident decision-making capacity compared with 26% of homes
      without a committee. Overall, 24% of residents were thought to have executed an
      advance directive. The number of directives per bed did not vary significantly by
      facility size, ownership, religious affiliation, or whether they did or did not
      have an ethics committee. CONCLUSIONS: The fact that social workers in nursing
      homes speak with most residents about advance directives has the potential to
      improve resident understanding around end of life decisions. The practice of not
      informing residents about advance directives when they are perceived to lack
      decision-making capacity is problematic given that most homes have no clear
      procedures for determining residents' cognitive capacity to execute a directive.
      There is a need to replicate the benefits achieved by homes with ethics
      committees in implementing the PSDA in other homes.

PMID- 8994488
TI  - The association between human leucocyte antigens (HLA) and mortality in community
      residents aged 85 and older.
AB  - OBJECTIVE: The association between Human Leucocyte Antigens (HLA) and aging was
      investigated. It is possible that HLA antigens are associated with longevity,
      either indirectly through disease associations or directly through involvement in
      the aging mechanism. DESIGN: Community-based follow-up study. SETTING: Leiden,
      the Netherlands. PARTICIPANTS: A total of 919 subjects were HLA typed in this
      community-based study. All subjects were aged 85 and older and were white.
      Seventy-two percent of the cohort was female. MEASUREMENTS: Age- and sex-adjusted
      Mortality Rate Ratios (MRR) were estimated for 79 antigens by the subject-years
      method. HLA-A, -B and -C typing was performed with the standard NIH
      lymphocytotoxicity test, HLA-DR and -DQ typing was performed with the two-color
      fluorescence test. Homozygosity for HLA-A, -B, and -DR was defined as only one
      detectable antigen at a locus. RESULTS: The mean follow-up period (SD) was 5.0
      (0.6) years. At the end of the follow-up, 70% of the subjects had died. The MRR
      (95% CI) for B60 was 0.96 (0.75-1.23), and for DR11 it was 0.82 (0.66-1.01). For
      A2 and A26 only, the MRR (95% CI) was significantly different from 1: 0.85 (0.73
      0.99), P = .04 and 1.45 (1.06-1.99), P = .02, respectively (P values not
      corrected for the number of antigens tested). Homozygosity was not associated
      with mortality. CONCLUSIONS: HLA was not associated with mortality after the age
      of 85. Therefore, direct involvement of HLA in aging is unlikely. We suggest that
      the findings of previous studies are attributable to methodological shortcomings
      such as small sample size and differences in genetic background of the subjects.

PMID- 8994489
TI  - Foot position awareness in younger and older men: the influence of footwear sole
      properties.
AB  - OBJECTIVES: To test the hypotheses that foot position awareness is related
      positively to stability, positively to shoe sole hardness, and negatively to shoe
      sole thickness, and that foot position awareness declines with advancing years.
      SETTING: Older subjects were consecutive volunteers from a medical clinic;
      younger subjects were volunteers from the community. DESIGN: Randomized-order,
      cross-over, controlled comparison. PARTICIPANTS: Older subjects were a random
      sample of 13 healthy men, mean age 72.58 years, SD +/- 4.50. Younger subjects
      were a random sample of 13 male subjects from the general population, mean age
      28.13 years, SD +/- 3.96. Additional selection criteria were absence of
      disabilities influencing ability to walk and no history of frequent falls.
      MEASUREMENTS: Balance failure frequency, defined as falls per 100 meters of beam
      walking; rearfoot angle in degrees, measured via an optical position measurement
      system; perceived maximum supination when walking, in degrees, estimated by
      subjects using a ratio scale; foot position error, in degrees, was defined as the
      rearfoot angle minus perceived maximum supination. RESULTS: Foot position error
      during walking: (1) increases with advancing years; footwear conditions absolute
      mean error for older sample of 15.48 degrees, SE +/- 1.56 degrees, and younger
      sample 5.44 degrees, SE +/- 1.03 degrees (P > .001); (2) is positively related to
      stability (r = .367, P < .001); (3) is positively related to midsole thickness
      (F(1,11) = 19.89, P < .001); (4) is negatively related to midsole hardness
      (F(2,22) = 29.80, P < .001); (5) correlates best with perceived maximum
      supination (r = .901, P < .001). CONCLUSION: Foot position awareness is related
      causally to stability; shoes with thin, hard soles provide better stability for
      men than those with thick, soft midsoles. Foot position awareness declines with
      advancing years.

PMID- 8994490
TI  - An analysis of the use of the telephone in the management of patients in skilled
      nursing facilities.
AB  - OBJECTIVE: To characterize the nature of telephone communication in the care of
      patients in skilled nursing facilities, noting numbers of calls, reasons for
      communication, and the outcomes of the interactions, and to implement a voice
      mail system to manage the burden of communication more effectively and describe
      the impact of this system. DESIGN: An archival descriptive study of phone message
      data covering a period of 1 year in a defined population of nursing home
      patients, with an intervention and an evaluation of a voice mail system at the
      conclusion of the year's study. SETTING: A long-term care practice associated
      with an urban family practice residency program. PARTICIPANTS: Medical care
      providers, the staffs of 13 skilled nursing facilities, and an average of 207
      covered patients followed for 1 year. INTERVENTION: At the termination of the
      descriptive study, a voice mail system was instituted, and the impact on phone
      communication was documented. MAIN OUTCOME MEASURES: Total numbers of calls were
      tabulated by patient and by facility. Reasons for calls, outcomes, and timing
      were tabulated. The impact of a voice mail system on the communication between
      nursing home staff and medical providers was characterized. RESULTS: A total of
      10,264 calls were received from 13 skilled nursing facilities in regard to an
      average of 207 continuously covered long-term care patients, which is an average
      of nearly 50 calls per patient per year. Acute illness accounted for only 5% of
      calls, and most communications were routine. Though a new treatment was
      instituted about one-third of the time, no new order was issued in response to
      23% of received calls. Hospitalization occurred as the result of about one in two
      hundred calls. A recent tabulation of 692 calls received during 1 month revealed
      that 93% of calls are now received through voice mail and about one in five of
      these calls do not need to be returned. CONCLUSIONS: There is a significant
      telephone call burden associated with care of patients in skilled nursing
      facilities. Most of these calls are routine, regulation driven, and often no
      return call is necessary. For many reasons, including poor reimbursement, much of
      the medical care delivered occurs as a result of these calls, and methods of
      managing the communication burden to allow prioritization both by the staff nurse
      and the physician need to be found. In the practice described, the voice mail
      system is a positive step in this direction.

PMID- 8994491
TI  - The impact of thiazide diuretics on the initiation of lipid-reducing agents in
      older people: a population-based analysis.
AB  - OBJECTIVE: The objective of this study was to examine how often treatment for
      hyperlipidemia followed the use of thiazides, compared with the use of other
      antihypertensive drugs, in older patients. DESIGN: Retrospective follow-up of all
      health claims filed over a 12-month period. SETTING: New Jersey Medicaid and
      Medicare programs. PARTICIPANTS: A total of 9274 enrollees, aged 65 to 99, who
      were newly initiated on antihypertensive medications from 1981-1989.
      MEASUREMENTS: We measured rates of lipid-reducing agent (LRA) initiation among
      patients in the 2 years following antihypertensive initiation (thiazide, non
      thiazide drug, or combinations of the two) compared with rates among patients not
      currently taking antihypertensive agents. We used Cox regression analyses to
      estimate relative risks (RR), accounting for switching in antihypertensive
      therapy and for time when drug therapy was not currently available according to
      pharmacy refill records. RESULTS: There were 226 patients (2.4%) in the cohort
      who were started on LRA during the follow-up period. After adjusting for
      potential confounders, we found no significant relationship between LRA
      initiation and overall thiazide use (RR 1.47, 95% CI 0.89-2.40), or other
      antihypertensive use, relative to no current exposure. However, use of high-dose
      thiazides (> or = 50 mg) was associated significantly with LRA initiation (RR
      1.97, 95% CI 1.12-3.45). Factors associated with decreased incidence of LRA use
      included age > or = 85 (RR 0.59, 95% CI 0.36-0.96), black race (RR 0.58, 95% CI
      0.37-0.91), and nursing home residency (RR 0.20, 95% CI 0.11-0.35). CONCLUSION:
      Use of low-cost and effective thiazide diuretics in older hypertensives was not
      associated with more common initiation of lipid-reducing agents, except with high
      dose use of thiazides currently seen as inappropriate in most cases. Age and race
      were important determinants of LRA use.

PMID- 8994492
TI  - Sexual violence, post-traumatic stress disorder and dementia.
AB  - Little is known of Post-Traumatic Stress Disorder (PTSD) in older people. No
      literature exists on this disorder in older women exposed to sexual assault. A
      case of apparent PTSD in a demented woman raises questions of the anatomy and
      phenomenology of this disorder. Difficulties in diagnosis in a demented
      population may cloud the issues or prevent a proper therapeutic outcome.

PMID- 8994493
TI  - Assessing capacity to participate in discussions of advance directives in nursing
      homes: findings from a study of the Patient Self Determination Act.
AB  - OBJECTIVE: To better understand the implementation of the Patient Self
      Determination Act (PSDA) in long-term care, with a focus on the informing process
      as it affects advance directives. DESIGN: Retrospective cohort study of nursing
      home admissions, using medical record reviews, and a companion qualitative survey
      using key informant interviews. SETTING: Eleven nursing homes in Connecticut.
      PARTICIPANTS: A total of 600 residents randomly selected from six randomly chosen
      nursing homes and 19 key informants selected from five purposely sampled nursing
      homes in Connecticut. MEASURES: Institutional compliance with the PSDA
      requirement to provide written information about advance directives at admission
      and aspects of the informing process, including to whom the information is given.
      RESULTS: Compliance with the PSDA requirement to provide information at admission
      is high (90.7 of admissions in the post-PSDA cohort received information within 1
      week of admission). However, in nearly 70% of admissions in which information was
      provided, someone other than the residents received the information. Staff often
      cited the resident's cognitive impairment as a reason for excluding residents
      from this informing process. However, even among those residents judged to be
      alert and oriented at admission, someone other than the resident received the
      information 47.7% of the time. CONCLUSIONS: Substantial numbers of residents may
      be inappropriately excluded from participating in discussions because of
      difficulties in determining decisional capacity to discuss future treatment
      wishes. The research highlights the difficulties of enhancing resident
      participation and autonomy in long-term care through procedural regulations such
      as the PSDA. More reliable methods of determining resident decisional capacity
      are needed to integrate the full intent of the PSDA into clinical practice in
      long-term care.

PMID- 8994494
TI  - A survey of habitual snoring in centenarians.
AB  - OBJECTIVE: To ascertain whether centenarians in the surveyed group would be
      nonhabitual snorers. DESIGN AND SETTING: A cross-sectional survey of centenarians
      residing in the Aichi Prefecture of Japan. PARTICIPANTS: A total of 103
      centenarians (21 men and 82 women). MEASUREMENTS: Questionnaire on sleep habits,
      breathing, and snoring. RESULTS: Nineteen centenarians (18.4%; 5 men and 14
      women) were habitual snorers and two (1.9%) were suspected of having sleep apnea
      syndrome because of the presence of heavy snoring and nocturnal respiratory
      arrest. CONCLUSION: Most centenarian subjects were nonsnorers and without
      breathing pauses during sleep; their snoring rates were no different from those
      of younger aged older adults in the same population.

PMID- 8994495
TI  - Post-hospital sub-acute care: an example of a managed care model.
AB  - OBJECTIVE: This article describes Transitional Care Centers (TCC), an innovative
      sub-acute care program developed by a large managed care organization
      (HealthPartners in Minnesota) in partnership with five area nursing homes. The
      purpose of the TCC is to promote continuity of care for frail older members
      covered under a TEFRA risk contract. DESIGN: This is a retrospective study of the
      experiences and outcomes of enrollees who received TCC compared with a like group
      of enrollees who received customary continuity care through contract services.
      SETTING: The TCCs are established contractually in five area nursing homes; these
      facilities keep at least 15 beds available to the health plan for round-the
      clock, 7 days per week admissions for sub-acute care. Designated staff from these
      facilities and designated geriatric nurse practitioners and geriatricians from
      HealthPartners follow established targeting, admissions, assessment, care
      planning, and discharge planning procedures to provide team care for these
      patients at the facilities. PARTICIPANTS: The TCC program is targeted to patients
      requiring rehabilitation therapy (post-cardiovascular accident, post
      fracture/replacement) who are deconditioned, or those with uncomplicated
      infections (urinary tract infection, pneumonia). A total of 1144 patients
      participated in the TCC program in the 1-year program under report, and 253 were
      surveyed in regard to their experience. One hundred HealthPartners physicians
      were surveyed about the program. RESULTS: Post-acute length of stay in the TCC
      was substantially lower than that in customary care settings in contract nursing
      homes (14.3 versus 20.5 days). Rehospitalization rates from these units were
      comparable to or better than those from other sub-acute units. Patient and
      primary care physician satisfaction with the units was high. The program provided
      economic benefit to both partners. The health plan's negotiated rate for the TCC
      units was 38% less than that paid in noncontractual facilities. CONCLUSION: The
      TCC partnership provides rehabilitative and geriatric evaluation services in
      settings more conducive to and less costly than such care usually, and yields
      improvements in care and utilization outcomes.

PMID- 8994496
TI  - Disability in older adults: evidence regarding significance, etiology, and risk.
AB  - OBJECTIVES: This article synthesizes and assesses current evidence about the
      importance of physical disability to older adults. It then considers the
      applications of research findings to clinical geriatrics practice. RESULTS:
      Physical disability is a major adverse health outcome associated with aging.
      Certain subgroups of older adults, including individuals with mobility
      difficulty, with preclinical functional changes, and persons who are
      hospitalized, are at particularly high risk of becoming disabled or experiencing
      disability progression. The major underlying causes of physical disability are
      chronic diseases, including both acute events, such as hip fracture and stroke
      and slowly progressive diseases such as arthritis and heart disease. These
      diseases appear to have task-specific effects; understanding this may assist in
      setting treatment and prevention goals. Comorbidity, particularly certain
      combinations of chronic diseases, is a strong risk factor for disability in
      itself. Recent trials indicate that clinical interventions may be able to prevent
      onset or progression of disability. CONCLUSIONS: Available evidence now suggests
      clinical approaches to both treatment and prevention of disability and directions
      for defining optimal clinical care for the future.

PMID- 8994497
TI  - S/HMOs, the second generation: building on the experience of the first Social
      Health Maintenance Organization demonstrations.

PMID- 8994498
TI  - The state of geriatrics training programs: findings from the National Study of
      Internal Medicine Manpower (NaSIMM)

PMID- 8994499
TI  - A report card on geriatrics fellowship training programs.

PMID- 8994500
TI  - Forsaking the spirit for the letter of law: advance directives in nursing homes.

PMID- 8994501
TI  - Appropriate content for discussion.

PMID- 8994502
TI  - Fellowship training.

PMID- 8994503
TI  - Assessment of mobility and ADL dependence following hip fracture surgery.

PMID- 8994504
TI  - Stability of age-associated memory impairment during a longitudinal population
      based study.

PMID- 8994505
TI  - Serum cholesterol levels and cognitive function assessed by P300 latencies in an
      older population living in the community.

PMID- 8994506
TI  - Depression in dementia sufferers--comparison of diagnostic criteria.

PMID- 8994507
TI  - Normalization of low vitamin B12 serum levels in older people by oral treatment.

PMID- 8994508
TI  - Autoantibodies against oxidized low-density lipoproteins in older stroke
      patients.

PMID- 8994509
TI  - Bridging study of S12024 in 53 in-patients with Alzheimer's disease.

PMID- 8994511
TI  - Suspended particulate matter and health: new light on an old problem.

PMID- 8994510
TI  - Leukotriene B4 and asthma.

PMID- 8994512
TI  - Effect of a leukotriene B4 receptor antagonist, LY293111, on allergen induced
      responses in asthma.
AB  - BACKGROUND: Leukotriene (LT) B4 is a potent neutrophil chemoattractant and also
      stimulates eosinophils in vitro, but its role in asthmatic inflammation is
      unknown. METHODS: The effect of the novel LTB4 receptor antagonist, LY293111, was
      examined using allergen challenge as a model for asthmatic inflammation in 12
      atopic asthmatic subjects in a double blind placebo controlled crossover trial.
      Subjects with an established early (EAR) and late asthmatic response (LAR) to
      allergen at screening received oral LY293111 in a dose of 112 mg three times
      daily for seven days or placebo before further allergen challenge. Each treatment
      was separated by a washout period of 28 days. Individuals underwent histamine
      challenge one hour before and three hours after allergen challenge.
      Bronchoalveolar lavage (BAL) fluid was obtained at bronchoscopy 24 hours after
      allergen challenge. RESULTS: There was no difference in baseline lung function,
      EAR, LAR, or in airway responsiveness to histamine before and after allergen
      between placebo and LY293111. By contrast, treatment with LY293111 significantly
      reduced the number of neutrophils in BAL fluid expressed as both absolute cell
      numbers and percentage cell differential counts: absolute cell counts, median
      (range) 0.04 (0.02-0.15) x 10(6) after LY293111, 0.09 (0.02-0.43) x 10(6) after
      placebo; percentage differential cell counts 0.35 (0.1-2.0) after LY293111, 0.80
      (0.1-3.6) after placebo (p < 0.05). Eosinophils, macrophages, and lymphocytes in
      BAL fluid did not differ between treatments. There was a significant reduction in
      the concentration of myeloperoxidase (MPO) with both placebo (16 (6.6) ng/ml) and
      LY293111 (3.5 (1.8) ng/ml) and of LTB4 (placebo 4.6 (1.2) pg/ml, LY293111 2.2
      (0.2) pg/ml). Concentrations of LTC4 and interleukin 8 were reduced, although not
      significantly, whereas concentrations of interleukin 6, GM-CSF, and TNF-alpha
      were unchanged by LY293111. CONCLUSIONS: These results demonstrate an influence
      of LTB4 on neutrophil influx and activation in the airway following allergen
      challenge. Despite this anti-inflammatory effect, there was no measured
      physiological benefit and this questions the functional role of the neutrophil in
      the pathophysiology of allergen induced asthma.

PMID- 8994513
TI  - Effect of allergen challenge on airway responsiveness to histamine and sodium
      metabisulphite in mild asthma.
AB  - BACKGROUND: Airway responsiveness to histamine and methacholine, direct smooth
      muscle spasmogens, is increased following inhalation of allergen. Although the
      aetiology of this phenomenon is unclear, increased cellular or neural activity
      may be involved since allergen also induces increases in airway responsiveness to
      the mast cell stimulus adenosine-5'-monophosphate (AMP) and the neural stimulus
      bradykinin. METHODS: To explore this further, the airway responsiveness to sodium
      metabisulphite (MBS), an indirect neural stimulus with similar characteristics to
      bradykinin, was compared in 18 mild steroid-naive asthmatic subjects with the
      airway responsiveness to histamine before and after allergen challenge with
      extracts of house dust mite, grass pollen, or cat. All subjects inhaled doubling
      increments of histamine and MBS until the concentration provoking a 20% fall in
      forced expiratory volume in one second (PC20) was reached before and three hours
      after allergen challenge. Twelve of the subjects had additional challenges at 24
      hours after the allergen. RESULTS: Following allergen challenge all subjects
      showed an early response and 14 also had a late asthmatic response. For histamine
      there was a significant increase in airway responsiveness at both three and 24
      hours compared with values before the allergen (0.89 (0.25) and 1.53 (0.52)
      doubling dose changes, respectively). In contrast, airway responsiveness to MBS
      was unaltered by allergen challenge (0.29 (0.27) and -0.33 (0.28) doubling dose
      changes compared with pre-allergen values at three and 24 hours, respectively).
      CONCLUSION: These data suggest that activation of airway sensory nerves is
      unlikely to contribute to the increase in airway responsiveness following
      inhalation of allergen. The previously observed allergen induced increase in
      airway responsiveness to bradykinin and AMP may involve non-neural pathways.

PMID- 8994514
TI  - Histamine induced bronchoconstriction and end tidal inspiratory activity in man.
AB  - BACKGROUND: End tidal inspiratory activity (ETIA) in diaphragm and parasternal
      intercostal muscles can be evoked in man and in animals by administration of
      histamine. Exacerbations of asthma and administration of histamine are often
      accompanied by hyperinflation. The aims of the study were to determine (1) the
      magnitude of ETIA in response to histamine in man, (2) the relative contributions
      of chemical and mechanical stimulation of airway receptors to ETIA, and (3) the
      importance of ETIA to hyperinflation. METHODS: The effects of inhalation of
      histamine on the electrical activities of the diaphragm and parasternal
      intercostal muscles measured with surface electrodes were studied in 21 subjects.
      The experiments were repeated after inhalation of 600 micrograms of salbutamol to
      prevent histamine induced bronchoconstriction and concomitant mechanical
      stimulation of airway receptors. Subjects were connected to a closed breathing
      circuit to measure the changes in functional residual capacity (FRC) for the
      different experiments. RESULTS: The mean values of histamine induced ETIA were
      60.6% and 46.9% of peak inspiratory activities during control conditions for the
      diaphragm and intercostal muscles, respectively. After salbutamol histamine
      induced ETIA was reduced to about one quarter of pre-salbutamol values. FRC
      increased by 427 ml as a result of inhalation of histamine, but after salbutamol
      this increase was only 53 ml. The data for ETIA and FRC were interpreted as
      indicating that the contributions of airflow limitation and ETIA to histamine
      induced hyperinflation are comparable. CONCLUSIONS: Histamine is a forceful
      stimulus for inducing ETIA. Both chemical and mechanical stimulation of airway
      receptors contribute to evoke ETIA, of which the contribution of mechanical
      stimulation is the more important one. ETIA contributes substantially to
      histamine induced hyperinflation.

PMID- 8994515
TI  - Potentiation of the bronchoprotective effects of vasoactive intestinal peptide,
      isoprenaline, and theophylline against histamine challenge in anaesthetised
      guinea pigs by adrenomedullin.
AB  - BACKGROUND: Adrenomedullin is a hypotensive peptide recently discovered in human
      phaeochromocytoma which has been found to inhibit bronchoconstriction induced by
      histamine and acetylcholine. This study was designed to determine the manner in
      which adrenomedullin and other bronchodilators interact in modulating airway
      function. METHODS: A study was undertaken to determine whether adrenomedullin
      potentiated the bronchoprotective effects of isoprenaline, vasoactive intestinal
      peptide (VIP), and theophylline against histamine-induced bronchoconstriction in
      anaesthetised guinea pigs in vivo. RESULTS: Adrenomedullin in a concentration of
      10(-9) M significantly inhibited histamine-induced bronchoconstriction but in a
      concentration of 10(-10) M it did not exhibit the bronchoprotective effect
      against histamine. VIP (10(-9) M) did not affect histamine-induced
      bronchoconstriction but it markedly inhibited the bronchoprotective effect
      against histamine in the presence of adrenomedullin (10(-10) M). VIP (10(-6) M)
      significantly inhibited histamine-induced bronchoconstriction but this effect was
      short lived. Adrenomedullin in a concentration of 10(-10) M potentiated
      bronchoprotection induced by VIP (10(-6) M) and prolonged it. Isoprenaline (10(
      8) M) also significantly inhibited histamine-induced bronchoconstriction and this
      effect was enhanced in the presence of adrenomedullin (10(-10) M). Similarly,
      adrenomedullin (10(-10) M) significantly potentiated theophylline-induced
      bronchoprotection, and a sub-bronchoprotective dose of theophylline (20 mg/kg
      i.p.) was effective in preventing histamine-induced bronchoconstriction in the
      presence of adrenomedullin (10(-10) M). CONCLUSIONS: This study shows that
      adrenomedullin potentiates the bronchoprotective effects of different classes of
      bronchodilators against histamine challenge in anaesthetised guinea pigs.

PMID- 8994516
TI  - Binding of Aspergillus fumigatus spores to lung epithelial cells and basement
      membrane proteins: relevance to the asthmatic lung.
AB  - BACKGROUND: Aspergillus fumigatus is an opportunistic pathogen to which asthmatic
      subjects are particularly susceptible. The ability of spores of A fumigatus to
      bind to pulmonary cells and basement membrane proteins was investigated to
      determine the mechanisms involved in this susceptibility. METHODS: Cells of the
      A549 pulmonary epithelial cell line or purified basement membrane proteins were
      immobilised on the wells of microtitre plates. They were then exposed to spores
      of A fumigatus in suspension, with or without various pretreatments of the
      spores, cells, and proteins. Adherent spores were counted by light microscopy.
      RESULTS: Spores of A fumigatus bound in a concentration dependent manner to A549
      epithelial cells and pretreatment of cells with interferon gamma (2500 units/ml)
      caused a significant doubling of spore binding. Binding of spores to A549 cells
      was inhibited by about a third by pre-incubation of the spores with fibrinogen
      (100 micrograms/ml). Spores bound specifically to extracellular matrix (ECM)
      components laid down by A549 cells, and pretreatment of the ECM components with
      hydrogen peroxide (25-80 microM) enhanced spore binding by approximately one
      third. They also bound specifically and in a saturable manner to purified
      fibrinogen, fibronectin, laminin, type I collagen, and type IV collagen. Pre
      incubation of spores with Arg-Gly-Asp tripeptide (RGD; 50-200 micrograms/ ml)
      inhibited binding to fibronectin and type I collagen by 50%. CONCLUSIONS: This
      study suggests that the presence of activated epithelial cells and the exposure
      of basement membrane that occurs in asthma, together with oxidant stress, may
      facilitate the colonisation of the asthmatic lung by A fumigatus. The RGD
      sequence may be involved in spore binding to some ECM proteins. Free fibrinogen
      may protect against binding of A fumigatus spores to the pulmonary epithelium.

PMID- 8994517
TI  - Effect of contact avoidance or treatment with oral prednisolone on
      bronchoalveolar lavage surfactant protein A levels in subjects with farmer's
      lung.
AB  - BACKGROUND: Surfactant protein A (SP-A) acts as an immune system modulator in the
      lungs and may therefore be involved in the pathogenesis of hypersensitivity
      pneumonitis. METHODS: The levels of SP-A in bronchoalveolar lavage (BAL) fluid
      were measured in 20 subjects with acute farmer's lung, 16 asymptomatic dairy
      farmers, and 14 normal controls. Eight patients had a second evaluation after one
      month of treatment by either contact avoidance (n = 3) or oral prednisolone (20
      or 25 mg/day, n = 5). Chest radiographs and lung function measurements were also
      obtained in all farmers, twice in those re-evaluated after treatment. RESULTS:
      Patients with acute farmer's lung had significantly higher levels of SP-A than
      asymptomatic farmers and normal controls (p = 0.005) with mean (SE) values of
      1.43 (0.29) micrograms/ml, 0.62 (0.09) microgram/ml, and 0.68 (0.11)
      microgram/ml, respectively. In eight subjects tested after one month of treatment
      the level of SP-A was unchanged although all were clinically improved. No
      correlations were seen between levels of SP-A in BAL fluid and numbers of BAL
      cells, lung function measurements, or chest radiographic scores. CONCLUSION:
      Although the level of SP-A is increased in the BAL fluid of patients with acute
      farmer's lung, it is not correlated with clinical abnormalities of this disease.

PMID- 8994518
TI  - Free radical activity and pro-inflammatory effects of particulate air pollution
      (PM10) in vivo and in vitro.
AB  - BACKGROUND: Epidemiological evidence has implicated fine particulate air
      pollution, particularly particles less than 10 microns in diameter (PM10), in the
      development of exacerbations of asthma and chronic obstructive pulmonary disease
      (COPD) although the mechanism is unknown. The hypothesis that PM10 particles
      induce oxidant stress, causing inflammation and injury to airway epithelium, was
      tested. METHODS: The effects of intratracheal instillation of PM10 was assessed
      in rat lungs (three per group). Inflammatory cell influx was measured by
      bronchoalveolar lavage (BAL) and air space epithelial permeability was assessed
      as the total protein in BAL fluid in vivo. The oxidant properties of PM10
      particles were determined by their ability to cause damage to plasmid DNA and by
      changes in reduced (GSH) and oxidised (GSSG) glutathione. The effects of PM10
      particles were compared in some experiments with those of fine (CB) and ultrafine
      (ufCB) carbon black particles. RESULTS: Six hours after intratracheal
      instillation of PM10 there was an influx of neutrophils (up to 15% of total cells
      in BAL fluid) into the alveolar space, increased epithelial permeability, the
      mean (SE) total protein in the BAL fluid increasing from 0.39 (0.01) to 0.62
      (0.01) mg/ml, and increased lactate dehydrogenase (LDH) concentrations in the BAL
      fluid. An even greater inflammatory response was seen following intratracheal
      instillation of ufCB but not following CB instillation. PM10 particles had free
      radical activity in vivo, as shown by a decrease in GSH levels in the BAL fluid
      from 0.36 (0.05) to 0.25 (0.01) nmol/ml following instillation. The free radical
      activity of PM10 was confirmed in vitro by its ability to deplete supercoiled
      plasmid DNA, an effect which could be reversed by mannitol, a specific hydroxyl
      radical scavenger. BAL fluid leucocytes from rats treated with PM10 produced
      greater amounts of nitric oxide (NO), measured as nitrite (control 3.07 (0.33),
      treated 4.45 (0.23) microM/1 x 10(6) cells), and tumour necrosis factor alpha
      (control 21.0 (3.1), treated 179.2 (29.4) units/l x 10(6) cells) in culture than
      those obtained from control animals. Since the PM10 preparation was contaminated
      with small amounts of filter fibres due to the extraction process, the effects of
      instillation of filter fibres alone was assessed. These studies showed that
      filter fibres did not account for the proinflammatory and injurious effects of
      the PM10 suspension. CONCLUSIONS: These findings provide evidence that PM10 has
      free radical activity and causes lung inflammation and epithelial injury. These
      data support the proposed hypothesis for the mechanism by which particulate air
      pollution causes adverse effects in patients with airways diseases.

PMID- 8994519
TI  - Eicosanoid mediator expression in mononuclear and polymorphonuclear cells in
      normal subjects and patients with atopic asthma and cystic fibrosis.
AB  - BACKGROUND: Eicosanoids such as leukotrienes, prostaglandins, lipoxins, and 15
      hydroperoxyeicosatetraenoic acid (15-HETE) cause bronchoconstriction, increased
      microvascular permeability, mucus secretion, and polymorph chemotaxis. These pro
      inflammatory effects are important in diseases such as asthma and cystic fibrosis
      where the levels of mediators are increased both in the stable and acute state. A
      study was conducted to examine the expression of the mRNA for the enzymes of the
      eicosanoid pathways (5-lipoxygenase (5-LO), 5-lipoxygenase activating protein
      (FLAP), cyclo-oxygenases 1 and 2 (COX-1, COX-2), and 15-lipoxygenase (15-LO)) in
      normal subjects and in patients with stable atopic asthma and stable cystic
      fibrosis. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was
      used to examine the expression of total RNA for 5-LO, FLAP, COX-1, COX-2, and 15
      LO in peripheral blood polymorphonuclear cells and mononuclear cells from the
      three subjects groups. RESULTS: The expression of mRNA for 5-LO and FLAP was
      similar in normal subjects and in patients with asthma and cystic fibrosis. COX-1
      was increased in both cell types in asthmatic patients. COX-2 and 15-LO were
      increased in polymorphs of patients with atopic asthma but not in mononuclear
      cells. COX-2 and 15-LO were undetectable in either cell type in patients with
      cystic fibrosis whereas COX-1 levels in polymorphs were similar to those in
      patients with asthma. CONCLUSIONS: The increased leukotriene production in asthma
      and cystic fibrosis is not explained by an increase in transcription of 5-LO and
      FLAP. Transcription of 15-LO and COX-2 is increased in atopic asthma.
      Transcription of COX-1 is increased in both atopic asthma and cystic fibrosis.

PMID- 8994520
TI  - Modification of nasal membrane potential difference with inhaled amiloride and
      loperamide in the cystic fibrosis (CF) mouse.
AB  - BACKGROUND: In the airway of subjects with cystic fibrosis (CF) the combination
      of defective cAMP mediated chloride secretion and enhanced sodium absorption
      leads to dehydration of mucosal mucus and is reflected in an increased trans
      epithelial potential difference (PD). The airway secretions may be less viscid
      and easier to expectorate if sodium (and water) reabsorption is inhibited.
      METHODS: To evaluate the response to sodium blocking agents, changes in the nasal
      PD in 20 transgenic CF mice were compared with 14 control mice (MF1 strain)
      before and after administration of nebulised amiloride and loperamide (both in a
      concentration of 1 mmol/l). The duration of action for both drugs was also
      determined after a single inhaled dose of 1 mmol/l for two minutes. RESULTS: The
      median basal PD was -24 mV in controls and -28 mV in CF mice (p < 0.01). This
      fell in CF mice after amiloride and loperamide administration by 15 mV and 14 mV,
      respectively, compared with a decrease of 7 mV and 5.5 mV in controls (p < 0.01).
      There was no further change in PD when loperamide was given after amiloride. This
      suggests that loperamide and amiloride may act on sodium absorption via similar
      mechanisms. Loperamide had a longer duration of action after a single
      administration than amiloride. CONCLUSION: The administration of amiloride and
      loperamide reduces the transepithelial potential and inhibits sodium reabsorption
      in the CF mouse airway. Further studies are required to determine if the more
      prolonged action of loperamide could be of therapeutic use.

PMID- 8994521
TI  - Health perceptions and treatment adherence in adults with cystic fibrosis.
AB  - BACKGROUND: Clinical and demographic variables are poor predictors of treatment
      adherence. This study therefore examined the relationships between the patients'
      perception of their cystic fibrosis and their reported adherence to
      physiotherapy, exercise, pancreatic enzyme and vitamin therapies. METHODS: Sixty
      adults with cystic fibrosis completed the Health Perception Scale, Health Locus
      of Control Scale, and the Manchester Adult Cystic Fibrosis Compliance
      Questionnaire. RESULTS: Reported adherence to physiotherapy, exercise, pancreatic
      enzyme and vitamin therapies was not influenced by patients' perceptions of their
      past, current and future disease severity, or their perceived susceptibility to
      recurrent infections. The greater their level of worry regarding their disease,
      the more likely they were to adhere to their physiotherapy (p < 0.002),
      pancreatic enzyme (p < 0.001) and vitamin (p < 0.001) regimens. No difference
      between the exercise adherent and non-adherent groups emerged regarding their
      level of worry. Compared with patients who believed that they were in control of
      their health, those who believed that their cystic fibrosis was controlled by
      others (family and health professionals) reported greater levels of adherence to
      their physiotherapy (p < 0.001), pancreatic enzyme (p < 0.001) and vitamin (p <
      0.001) therapies. In contrast, patients who adhered to their exercise regimen
      believed that they were in control of their disease to a greater extent than
      those who did not (p < 0.003). CONCLUSIONS: Worrying about cystic fibrosis and
      the perception of having little personal control over the disease facilitated
      treatment adherence. It is clear that patients perceive exercise therapy
      differently from other forms of treatment.

PMID- 8994522
TI  - Clinical assessment of diaphragm strength by cervical magnetic stimulation of the
      phrenic nerves.
AB  - BACKGROUND: Accurate assessment of diaphragm strength can be difficult.
      Transdiaphragmatic pressure (PDI) measurements during volitional manoeuvres are
      useful but it may be difficult to ensure maximum patient effort. Magnetic
      stimulation of the phrenic nerves is easy to perform and the results are
      reproducible in normal subjects. The purpose of the present study was to evaluate
      the usefulness of magnetic stimulation of the phrenic nerves in the assessment of
      diaphragm weakness in patients. METHODS: Sixty-six patients referred for
      assessment of respiratory muscle strength and 23 normal subjects were studied.
      Twitch PDI (TwPDI) following magnetic stimulation of the phrenic nerves and
      sniffPDI were obtained in all individuals. TWPDI following bilateral electrical
      stimulation of the phrenic nerves was also obtained in eight patients. RESULTS:
      Mean (SD) TwPdi for the normal subjects was 31 (6) cm H2O and 18 (11) cm H2O for
      the patients. TwPDI and sniffPDI were correlated (r = 0.77). Seven of the 37
      patients (19%) with a reduced sniffPDI had a TwPDI within the normal range
      whereas two of the 32 patients (6%) with a reduced TwPDI had a normal sniffPDI.
      TwPDI was similar with magnetic and electrical stimulation. CONCLUSIONS: TwPDI
      following magnetic stimulation of the phrenic nerves is a clinically useful
      measurement when assessing diaphragm weakness.

PMID- 8994523
TI  - Pulmonary Mycobacterium kansasii infection: comparison of radiological
      appearances with pulmonary tuberculosis.
AB  - BACKGROUND: A study was undertaken to determine if there are differences in the
      radiological appearances at presentation between pulmonary infections caused by
      Mycobacterium kansasii and Mycobacterium tuberculosis. Correct recognition of the
      organism has important implications with regard to initial therapy and contact
      tracing. METHODS: The initial chest radiographs of 28 patients with pulmonary M
      kansasii infection were compared with those of 56 age, sex, and race matched
      patients with M tuberculosis infection. All patients in both groups were culture
      positive and none was known to be HIV positive. The radiographs were analysed
      independently by two radiologists who were unaware of the causative organism.
      RESULTS: Radiographic abnormalities in patients with M kansasii infection were
      more frequently unilateral and right side predominant, while those with
      tuberculosis more frequently involved a lower lobe. Air space shadowing involving
      more than one bronchopulmonary segment and pleural effusions were seen less
      frequently in M kansasii infection (four of 28 (14%) versus 30 of 56 (54%) and
      none of 28 versus 15 of 56 (27%)). Cavitation (21 of 28 (75%) versus 34 of 56
      (61%) was seen to a similar extent in patients with M kansasii infection and in
      those with tuberculosis. Cavities tended to be smaller in patients with M
      kansasii infection (p < 0.01). CONCLUSIONS: Differences are seen in the
      radiographic appearances of pulmonary infection caused by M kansasii and M
      tuberculosis. These differences are not sufficient to allow a positive diagnosis
      on the basis of radiographic findings alone, but the presence of a pleural
      effusion or lower lobe involvement makes M kansasii infection very unlikely.

PMID- 8994524
TI  - Pulmonary Mycobacterium kansasii infection: comparison of the clinical features,
      treatment and outcome with pulmonary tuberculosis.
AB  - BACKGROUND: In the United Kingdom Mycobacterium kansasii is the most common
      pulmonary non-tuberculous mycobacteria to cause disease in the non-HIV positive
      population. METHODS: The clinical features, treatment, and outcome of 47 patients
      (13 women) of mean (SD) age 58 (17) years with culture positive pulmonary M
      kansasii infection were compared with those of 87 patients (23 women) of mean
      (SD) age 57 (16) years with culture positive pulmonary M tuberculosis infection
      by review of their clinical and laboratory records. Each patient with M kansasii
      infection was matched for age, sex, race and, where possible, year of diagnosis
      with two patients with M tuberculosis infection. RESULTS: All those with M
      kansasii infection were of white race. Haemoptysis was more common in patients
      infected with M kansasii but they were less likely to present as a result of an
      incidental chest radiograph or symptoms other than those due to mycobacterial
      infection. Patients with M kansasii were also less likely to have a history of
      diabetes, but the frequency of previous chest disease and tuberculosis was
      similar. An alcohol intake of > 14 units/week was less frequent in those with M
      kansasii, but there were no significant differences in drug history, past and
      present smoking habit, occupational exposures, social class, or marital status.
      Patients with M kansasii received a longer total course of antimycobacterial
      therapy and, in particular, extended treatment with ethambutol and rifampicin was
      given. There was no significant difference in outcome between pulmonary M
      kansasii or M tuberculosis infection. CONCLUSIONS: There are group differences
      between the clinical features of the two infections but, with the possible
      exception of diabetes and alcohol intake, these features are unlikely to be
      diagnostically helpful. Treatment of M kansasii infection with ethambutol,
      isoniazid, and rifampicin in these patients was as effective as standard regimens
      given to patients infected with M tuberculosis.

PMID- 8994526
TI  - Time course from first symptom to treatment in patients with non-small cell lung
      cancer referred for radiotherapy: a report by the CHART Steering Committee.
AB  - BACKGROUND: Only a small proportion of patients with non-small cell lung cancer
      (NSCLC) attending radiotherapy centres were suitable for inclusion in a
      randomised trial which compared continuous hyperfractionated accelerated
      radiotherapy (CHART) with conventional radical radiotherapy. As this was thought
      to be partly due to delays in the referral of patients to clinical oncologists, a
      prospective study was performed to determine the interval between first report of
      symptoms and first radiotherapy treatment in patients with NSCLC. METHODS: The
      time course from first symptom to treatment was determined in all patients with
      NSCLC attending 10 cancer centres for radiotherapy to a primary tumour in a three
      month period. RESULTS: Only 5% of 484 patients were suitable for the trial of
      radical radiotherapy. The principal causes for exclusion were poor general
      condition (37%), too large a tumour (27%), and extrathoracic metastases (19%).
      The median time from first symptom to diagnosis was 13 weeks, from first symptom
      to first treatment 19 weeks, and from diagnosis to first treatment five weeks. In
      a quarter of the patients these intervals were greater than 25,33 weeks, and nine
      weeks, respectively. CONCLUSION: The reason for these long intervals needs
      investigation since earlier diagnosis and more immediate referral for
      consideration of treatment might increase the number of patients with NSCLC
      suitable for radical radiotherapy.

PMID- 8994525
TI  - Increased inflammatory cytokines and new collagen formation in cutaneous
      tuberculosis and sarcoidosis.
AB  - BACKGROUND: Interactions between mononuclear cells, vascular endothelium,
      fibroblasts, and cytokines during the inflammatory reaction within a granuloma
      have the potential to contribute to the progression to fibrosis. METHODS: Biopsy
      specimens of six tuberculous and eight sarcoidosis skin lesions were examined by
      immunohistochemistry to seek evidence for the presence of inflammatory and
      fibrotic reactions in human granulomatous disease. Additionally, to understand
      how a T cell mediated delayed type hypersensitivity reaction--a component of
      chronic granulomatous inflammation--could progress to fibrosis, the human in vivo
      model of the cutaneous tuberculin Heaf reaction to purified protein derivative
      (PPD) was studied in a group of 48 subjects. RESULTS: Granulomas from tuberculous
      and sarcoidosis skin biopsy specimens were seen to contain cells with marked
      staining by antibodies to fibronectin, transforming growth factor beta (pan TGF
      beta), and type 1 procollagen (PCP-1). Accentuated staining of extracellular
      matrix was seen both in the granulomas and in the peri-granulomatous regions.
      Less prominent staining was observed using antibodies against interleukin 1 beta
      (IL-1 beta) and alpha-smooth muscle actin (alpha-SMA). Biopsies of Heaf reactions
      revealed cells staining for IL-1 beta, tumour necrosis factor alpha (TNF-alpha),
      platelet derived growth factor B (PDGF-B), and fibronectin which were detected as
      early as day 1 and persisted throughout the 14 day study period. Cells staining
      for PCP-1 increased to greatest abundance at day 14. All these cytokines were
      present in low abundance in biopsy specimens from sites inoculated with saline
      only. CONCLUSIONS: Evidence is provided that granulomas in tuberculosis and
      sarcoidosis behave as active centres of fibrogenesis. Using the Heaf model, the
      temporal relationship between the early appearance of cytokines and the later
      increase in the collagen precursor PCP-1 linked the immune mediated chronic
      inflammatory response with subsequent fibrosis and suggested that the tuberculin
      Heaf reaction will serve as a model for studying the early events of granuloma
      formation in patients with tuberculosis and sarcoidosis.

PMID- 8994527
TI  - Factors affecting long term survival following resection for lung cancer.
AB  - BACKGROUND: Survival following pulmonary resection for primary lung cancer is
      considered to be principally dependent on the clinical stage of the disease. A
      study was undertaken to verify this and to identify other contributing factors.
      METHODS: The case records of all patients who underwent surgery for lung cancer
      over a two year period between January 1987 and December 1988 were reviewed
      retrospectively. RESULTS: One hundred and forty-seven lobectomies and 60
      pneumonectomies were performed with 2.8% and 5.3% operative mortality,
      respectively. Squamous carcinoma was the commonest pathology (60%) followed by
      adenocarcinoma (30%). The overall five year survival was 45.5% (95% CI 44.1% to
      57.9%). There were 123 patients with stage I disease, 40 with stage II, and 37 in
      stage IIIa with five year survival of 59.4% (95% CI 50.8% to 68%), 30% (95% CI
      15.9% to 44.1%), and 16.2% (95% CI 3.5% to 31%), respectively. There were no
      differences in survival with respect to sex, extent of resection, or cell type.
      In patients with stage II disease the five year survival of those with T1 lesions
      (50%, 95% CI 37.3% to 62.9%) was better than those with T2 (28.1%, 95% CI 16.9%
      to 39.3%). Of eight patients over the age of 70 with stage IIIa disease none
      survived more than 24 months. CONCLUSIONS: Stage at operation is the most
      accurate predictor of long term survival in early lung cancer and surgery remains
      an effective treatment, particularly in stage I and II disease. Further study is
      needed to assess the prognostic value of subdividing stage II disease into T1 and
      T2 lesions. Major resection for locally advanced disease in older patients may be
      relatively ineffective.

PMID- 8994528
TI  - Gastrin levels in serum and bronchoalveolar lavage fluid of patients with lung
      cancer: comparison with patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: The gastrin gene is known to be expressed in all classes of
      bronchogenic carcinomas. Furthermore, high levels of gastrin have been reported
      in both the bronchoalveolar lavage (BAL) fluid and serum of patients with lung
      cancer. Based on these preliminary data a study was conducted to evaluate the
      usefulness of gastrin measurements in the diagnosis and staging of lung cancer.
      METHODS: Thirty-five patients with lung cancer (26 non-small cell (NSCLC) and
      nine small cell (SCLC)) and 25 patients with chronic obstructive pulmonary
      disease underwent fibreoptic bronchoscopy and BAL. Gastrin levels were determined
      in both BAL fluid and the serum and compared with each other and with staging.
      RESULTS: No difference was found between the gastrin levels in the BAL fluid or
      serum of the study groups. There was no correlation with the stage in NSCLC and
      no correlation was found between the gastrin levels in the serum and the BAL
      fluid. A significant difference was seen in gastrin levels in BAL fluid between
      extensive and limited SCLC (p < 0.05). CONCLUSION: There is no evidence of
      clinical usefulness for gastrin measurements in lung cancer.

PMID- 8994529
TI  - Secretory leukoprotease inhibitor: partnering alpha 1-proteinase inhibitor to
      combat pulmonary inflammation.
AB  - Secretory leukoprotease inhibitor (SLPI) is a low molecular weight serine
      proteinase inhibitor, notably of neutrophil elastase (NE), which is synthesised
      and secreted by the pulmonary epithelium. SLPI plays an important role in
      limiting NE-induced pulmonary inflammation and, significantly, it also possesses
      anti-HIV activity. SLPI is a significant component of the anti-NE shield in the
      lung which has different reactivity from, and is therefore complementary to, the
      anti-NE action of alpha 1-proteinase inhibitor (alpha 1-PI). Inhaled recombinant
      SLPI (rSLPI) could prove beneficial in partnership with alpha 1-PI in the
      treatment of a number of inflammatory lung disorders including emphysema, chronic
      bronchitis, cystic fibrosis, and adult respiratory distress syndrome.

PMID- 8994530
TI  - Gorham's syndrome: a usually fatal cause of pleural effusion treated successfully
      with radiotherapy.
AB  - A 21 year old man presented with a right sided pleural effusion. Destruction of
      the 11th and 12th right ribs and adjacent vertebral bodies was noted on computed
      tomographic scanning. An open rib biopsy revealed the histopathological changes
      of Gorham's syndrome. In view of the progressive vertebral destruction and
      inevitable spinal cord compromise, he was treated with high dose radiotherapy.
      The process was arrested and he remains well with no signs of recurrence after
      four years. Pleural effusion and vertebral destruction complicating Gorham's
      syndrome carry a poor prognosis but, in this case, high dose radiotherapy has
      been effective in controlling both the effusion and the progressive bony
      destruction.

PMID- 8994531
TI  - Bilateral chylothorax complicating massive osteolysis (Gorham's syndrome)
AB  - Chylothorax may rarely occur in osteolysis. A fatal case of bilateral chylothorax
      complicating massive osteolysis is described and the pathogenesis and management
      are discussed.

PMID- 8994532
TI  - Young patient with Gorham's syndrome.

PMID- 8994533
TI  - Occupational asthma due to latex in health care workers.
AB  - Immediate hypersensitivity reactions ranging from mild urticaria to life
      threatening anaphylaxis after exposure to natural rubber latex have been reported
      frequently in health care workers while occupational asthma due to latex exposure
      is less well studied. The results of specific challenge tests and immunological
      tests in four health care workers with work related respiratory and skin
      disorders induced by the use of latex gloves are described. Occupational asthma
      was confirmed in three subjects by specific challenge tests. All had a positive
      skin test reaction to the latex extract; specific IgE antibodies were detected in
      only one subject. The fourth subject had a negative specific inhalation and skin
      test reaction to the latex extract. Peak expiratory flow monitoring at work and
      away from work showed a pattern consistent with work related asthma. These
      findings confirm that latex is a cause of occupational asthma in health care
      workers.

PMID- 8994535
TI  - Nebulised antipseudomonal therapy in cystic fibrosis.

PMID- 8994534
TI  - Spontaneous regression of a giant pulmonary bulla.

PMID- 8994537
TI  - Carl-Ludwig-Symposium. Leipzig, Germany, 18-20 May 1995.

PMID- 8994538
TI  - Carl Ludwig: the man, his time, his influence.
AB  - Carl Ludwig (1816-1895) was the driving force in the foundation and development
      of scientifically based and experimentally oriented physiology against natural
      philosophy and vitalism that prevailed during the first quarter of the 19th
      century in Germany. He was the representative of a small group of young, highly
      talented and dynamic physiologists aiming at implementing the laws of physics and
      chemistry as the only active forces in physiologic processes. These "organic
      physicists" included Emil du Bois-Reymond (1818-1896), Ernst Brucke (1819-1892),
      and Hermann Helmholz (1821-1894). Carl Ludwig wrote the program of this group in
      the form of a textbook of physiology that was considered revolutionary,
      provocative and premature. His academic life, his inventions and discoveries, his
      scientific achievements, his influence and his personality are reviewed. Since
      every person can be viewed only in the context of his time, the political
      background, the economic and social situation, the conditions for science and
      research as well as the cultural climate that were characteristic for the
      decisive years of Carl Ludwig are described to some extent. It is shown that Carl
      Ludwig and his contemporary organic physicists lived and grew into a science- and
      research-oriented period which had been prepared and paved by men like Johannes
      Evangelista Purkinje (1787-1869), Ernst Heinrich Weber (1795-1878), Alfred
      Wilhelm Volkmann (1800-1877), Johannes Muller (1801-1858) and Gustav Theodor
      Fechner (1801-1887). They benefited from this enormous scientific development and
      contributed to it to a large and significant extent so that it ultimately turned
      out to be the most productive and influential period in the history of German
      physiology. Some of the numerous scholars who had studied with Carl Ludwig
      carried his approach to physiology into the 20th century: Adolf Fick (1829-1901),
      Otto Frank (1865-1944), Iwan Petrowitsch Pawlow (1849-1936) and Henry Pickering
      Browditch (1840-1911).

PMID- 8994539
TI  - Relevance and reliability of Ludwig's scientific conceptions of the physiology of
      the microcirculation.
AB  - Modern research into the physiology of the blood circulation has been influenced
      decisively by Carl Ludwig. His contributions to the special field of
      microcirculation are typical examples of his scientific mode of thinking, being
      characterised by exactness and richness of ideas. His demand for a useful
      division of the complete circulatory system into two parts, namely the intra- and
      extravascular circulation, has remarkable heuristic value. His ideas concerning
      the functions of the extravascular space have maintained their validity up to the
      present day. His conception of the existence of open connections between the
      interstitial compartments and the inside of the lymphatic vessels was far ahead
      of contemporary knowledge: the relevant findings and ideas of Ludwig look, in
      part, like "confirmations" or anticipations of modern investigation results. This
      is illustrated by corresponding examples. As far as his scientific conceptions
      are concerned Ludwig was very particular to abstain from admission of any
      hypothetic throughts into them. The high reliability of his conceptions resulting
      from this custom is exemplified by comparing his interpretation of fluid and
      substance exchange in the terminal vessel area with "Starling's law" as the
      currently accepted explanation of these processes.

PMID- 8994540
TI  - Physiology with cool obsession: Carl Ludwig--his time in Vienna and his
      contribution to isolated organ methodology.
AB  - This short report presents new information on Carl Ludwig's move from Zurich to
      the chair of physiology in Vienna and the 10 years he spent here and
      characterizes some of his contributions to experimentation methodology in working
      with isolated organs. Two up to now unknown documents concerning his call to the
      chair of physiology and zoology at the Josephs Academy, a military academy; have
      been found in the Public Record Offices in Vienna: a secret service report and
      the letter of Ludwig with his conditions for accepting the appointment. Some
      characteristic sections are cited. The time in Vienna between 1855 and 1865 is
      depicted against the background of political processes in Europe after the 1848
      revolution. Ludwig's and his pupils' work with isolated organs is analysed
      briefly with some examples, especially relating to heart and kidney and a
      kymographion shown with a 20-channel registration module. The first "heart-lung
      machine" is discussed.

PMID- 8994541
TI  - Capillary perfusion in the brain.
AB  - The density of the total and the perfused capillary network was determined in the
      brains of awake, normocapnic rats. Perfused capillaries were marked by i.v. Evans
      blue. Existing capillaries were made visible by antibodies directed against the
      fibronectin portion of the capillary walls. Comparison of perfused and existing
      capillaries in identical brain sections by double staining showed a high degree
      of congruence between perfused and existing brain capillaries. The results show a
      continuous perfusion of all capillaries in the brain of the awake normocapnic
      rat. In the second group of experiments capillary perfusion was investigated
      during a reduction of cerebral blood flow induced by incomplete forebrain
      ischaemia. These experiments showed a gross preservation of capillary flow in the
      brain capillaries, although the velocity of perfusion was reduced. Finally, a
      method was developed which allows the distribution pattern of brain capillary
      plasma flow to be examined. The third group of experiments which used this method
      indicates a heterogeneous distribution of capillary flow in the brain under
      normocapnic conditions and a reduction of heterogeneity during hypocapnic
      hyperaemia.

PMID- 8994542
TI  - Activation of protein kinase C accelerates contraction kinetics of airway smooth
      muscle.
AB  - Contraction kinetics of isolated rat tracheal smooth muscle were studied by
      analysing the increase of force subsequent to force-inhibiting passive length
      changes lasting 1 s (100 Hz, sinus, 5% of muscle length). Compared with carbachol
      activation, phorboldibutyrate (PDBu)-induced stimulation of protein kinase C
      (PKC) demonstrated no significant difference in the extent of force development
      in the polarized preparation [mean peak force 9.16 +/- 0.37 mN (carbachol) vs.
      9.12 +/- 0.37 mN (PDBu)]. However, the time constant calculated for the slow
      component of post-vibration force recovery was 6.40 +/- 0.29 s after addition of
      PDBu vs. 22.39 +/- 1.40 s during carbachol activation, indicating a significant
      phorbol ester-induced acceleration of the cross-bridge cycling rate. In the K
      depolarized preparation, treatment with 26.4 microM indolactam (IL) to activate
      PKC produced muscle relaxation (9.94 +/- 0.16 mN measured 0-30 min after the
      onset of depolarization vs. 4.13 +/- 0.05 mN measured during 30-60 min of IL
      treatment). Again, even in the presence of high sarcoplasmic Ca2+ resulting from
      tonic depolarization, PKC activation was associated with a distinct diminution of
      the time constant (25.99 +/- 0.79 s during the first 30 min of depolarization vs.
      10.32 +/- 0.21 s during 30-60 min of IL treatment). In contrast, addition of
      0.035 microM verapamil, 1.5 microM isoproterenol, and 32 microM dibutyryl-cAMP to
      the bathing medium induced relaxation without affecting the rate of post
      vibration force recovery. The results suggest that the calcium-dependent signal
      cascade (agonist receptor/inositol trisphosphate/ Ca(2+)-calmodulin/myosin light
      chain kinase) hardly affects the regulation of contraction kinetics in the
      tonically activated intact smooth muscle preparation. PKC stimulation, however,
      accelerates actin/myosin interaction kinetics, possibly by inhibition of
      phosphatase(s).

PMID- 8994543
TI  - Calcium antagonism in vascular smooth muscle cells.
AB  - Ca2+ ions play critical roles in physiological and pathological signal
      transduction in vascular smooth muscle cells (VSMC). The control of Ca2+
      homeostasis is an important means for modulating excitability and response. A
      pathological increase of Ca(2+)-dependent vascular tone causes vasospasm and
      arterial hypertension. Moreover, Ca(2+)-mediated migration, proliferation, matrix
      production and necrotization of VSMC are important components of atherogenic
      plaque formation. At least two physiological Ca2+ antagonists are known that
      compete for Ca2+ binding sites at VSMC: H+ and Mg2+. Effective pharmacological
      control of Ca2+ homeostasis is exerted by organic Ca2+ antagonists. The
      prototypical compounds verapamil, nifedipine and diltiazem and their derivatives
      represent three separate structural categories of drugs that block
      transsarcolemmal Ca2+ influx by specific interaction at a set of binding sites
      associated with the alpha 1-subunit of the L-type, voltage-gated Ca2+ channel
      protein. Selectivity of action of the Ca2+ antagonists may arise from
      pharmacokinetics, class and subclass of the Ca2+ channel activated, state
      dependent interactions or pathological alterations. In human therapy they are the
      drugs of choice in the treatment of arterial spasms and hypertension. The extent
      to which their antiatherogenic properties are related to Ca2+ channel antagonism
      at VSMC remains to be elucidated further.

PMID- 8994544
TI  - Beta innervation and recurrent inhibition: a hypothesis for manipulatory and
      postural control.
AB  - The innervation of muscle spindles by skeletofusimotor (beta) axons in
      functionally different muscles of the cat forelimb has been correlated with the
      neural circuitry of the respective motor nuclei, morphological characteristics of
      their motoneurones and the innervated muscle fibres. In long digt extensor
      muscles a high degree of beta-innervation (more than 70%) and of fast contracting
      muscle fibres (more than 70% IIB fibres) correlates with specific projections of
      their Ia muscle spindle afferents, with the absence of a recurrent inhibitory
      system, with cell body diameters in the range of small alpha-motoneurones and
      with a short duration of their after-hyperpolarisations. In contrast, the
      investigated elbow muscles display a low degree of beta-innervation (41-47%)
      irrespective of their fibre type composition, their Ia afferent fibres show a
      divergent projection pattern and their motor nuclei a distinct recurrent
      inhibitory system. We suggest that for the distal muscles the specific
      combination of these different characteristics serves the control of manipulative
      movements, whereas for the proximal muscles the contrasting characteristics serve
      the control of posture and locomotion. This hypothesis is discussed in view of
      the phylogenetic development of motor control.

PMID- 8994545
TI  - Carl Friedrich Wilhelm Ludwig: the founder of modern renal physiology.
AB  - The revolutionary "Zeitgeist" in the Europe of the 1840s left its mark no less in
      science than it did in the social and political life of the population. The
      essence of the scientific revolution was the change in paradigm from a vitalist
      inductive to a mechanistic hypothetico-deductive approach, in which the
      experiment assumed the central role. The initiator of this new approach was a
      young physiologist in Marburg, Germany-Carl Friedrich Wilhelm Ludwig- and the
      first document his 1842 Habilitation thesis. Although this thesis was limited to
      a study on renal function, the impact of this epochal new approach, namely the
      analysis and explanation of living phenomena solely on the basis of physics and
      chemistry, went far beyond renal physiology: it revolutionised thinking in all
      the biological sciences. In this thesis, Carl Ludwig enunciated the principle of
      glomerular ultrafiltration driven by physical forces alone, i.e., the difference
      in the hydrostatic and oncotic pressures of the blood in the glomerular
      capillaries, a concept which remains valid today. Ludwig thus became the first
      scientist to describe correctly a principal component of renal function, the
      process of glomerular filtration.

PMID- 8994546
TI  - Controversies on glomerular filtration from Ludwig to the present.
AB  - Since Ludwig's theory of filtration in the glomerulus is generally accepted,
      current research interest has focussed on the regulation of this process. The
      main determinants of glomerular filtration rate are glomerular capillary pressure
      and glomerular blood flow, which are adjusted via resistance changes in the pre-
      and postglomerular vasculature. Overall pre- and postglomerular resistances were
      first determined by micropuncture in superficial glomeruli. While the predominant
      source of postglomerular resistance is the efferent arteriole, several results
      indicate that preglomerular resistance might be rather uniformly distributed
      among all preglomerular vessels (interlobar, arcuate and interlobular arteries
      and afferent arterioles). Over the last decade, several techniques have been used
      to visualize renal vessels and to study the action of various vasoactive hormones
      thereon. Results obtained with the split hydronephrotic kidney model, which
      permits in vivo microscopy of all renal vessels, provide evidence for a
      differential regulation of the various preglomerular vessels by vasoactive
      hormones. In particular, mediators of inflammation almost selectively constrict
      interlobar and arcuate arteries. We conclude that, given the renal vascular
      architecture, differential regulation of preglomerular vessels can alter
      haemodynamic parameters specifically for different nephron populations.

PMID- 8994547
TI  - The mechanisms of renal tubule electrolyte and water absorption, 100 years after
      Carl Ludwig.
AB  - Some 154 years after Carl Ludwig's Habilitationsschrift "Contributions to the
      theory of the mechanism of urine secretion" renal physiology has come a long way.
      The mechanisms of urine formation are now understood as the result of glomerular
      filtration and tubule absorption of most of the filtrate. The detailed
      understanding of tubule transport processes has become possible with the
      invention of several refined techniques such as the micropuncture techniques; the
      microchemical analysis of nanolitre tubule fluid samples; the in vitro perfusion
      of isolated tubule segments of defined origin; electrophysiological analysis of
      electrolyte transport including micropuncture and patch-clamp techniques;
      transport studies in membrane vesicle preparations; recordings of intracellular
      electrolyte concentrations and cloning techniques of the individual membrane
      transport proteins. With this wealth of information we are now starting to build
      an integrative understanding of the function of the individual nephron segments,
      the regulatory processes, the integrated function of the nephron and hence the
      formation of the final urine. Like anatomists of previous centuries we still
      state that the kidney is an "organum mirable" and we recognize that basic
      research in this area has fertilized the analysis of the function of a large
      number of other organs and cells.

PMID- 8994548
TI  - Plasticity of renal epithelial cells: the way a potassium channel supports
      migration.
AB  - In this article we review aspects of plasticity of renal epithelial cells. We
      focus on one particular feature, namely on cell migration. For normal renal and
      other epithelial cells migration is a motif of plasticity which can be activated
      after disrupture of epithelial integrity. In the case of transformed renal
      epithelial cells, however, migration is "pathophysiological" as it is no longer
      regulated as in normal cells. We studied migration in a permanently transformed
      Madin-Darby canine kidney cell line, called MDCK-F. Locomotion of these cells
      strictly depends-in addition to the cytoskeletal "migration machinery"-upon the
      oscillatory activity of a Ca(2+)-sensitive plasma membrane K+ channel. We propose
      that K+ channel activity is linked to migration via changes of cell volume. We
      deduced from patch-clamp experiments in combination with high resolution 3D
      images obtained by atomic force microscopy that periods of high K+ channel
      activity are parallelled by cell shrinkage. By locally superfusing either cell
      body (rear part) or lamellipodium (front part of the cell) with specific K+
      channel blockers we disclosed a polar distribution of K+ channel activity in MDCK
      F cells. K+ channels are preferentially active at the rear part of MDCK-F cells.
      We discuss how localized K+ channel activity, in concert with other migration
      relevant phenomena such as "tail contraction" or asymmetric cell-matrix
      interactions, may result in localized changes of cell volume supporting
      migration. Finally, we define cell polarization for a migrating epithelial cell.
      Whereas normal epithelial cells are "vertically" polarized, transformed cells are
      "horizontally" polarized, i.e., in the plane of movement. Such a distinct view
      could be helpful for better understanding the transition from a normal
      differentiated epithelial cell to a tumorigenic migrating cell.

PMID- 8994549
TI  - Carl Ludwig and the localization of the medullary vasomotor center: old and new
      concepts of the generation of sympathetic tone.
AB  - In Carl Ludwig's laboratories in Leipzig, P. Owsjannikow (1871) and C. Dittmar
      (1873) performed precise, histologically controlled lesioning experiments into
      the question of the location of the vasomotor center in the medulla oblongata. A
      small area in the ventrolateral parts of the medulla with its caudal border 3 mm
      cranial to the obex and an extension of 3-4 mm in cranial direction was described
      as the vasomotor area which has to be left intact for normal vasomotor tone and
      reflexes. This finding, ignored for more than 100 years, is the most precise
      description of what is known today as the location of spinally projecting
      sympatho-excitatory neurones, named the RVML region. Already in these early
      publications the question of the origin of basic vasomotor tone within these
      areas was raised and the possibilities of automaticity and reflexogenic input
      were discussed. Both possibilities are still valid today and under current
      investigation. A specific chemosensitivity of the RVLM neurones has been
      demonstrated during the recent decade and its role with regard to the generation
      of the sympathetic tone and the nervous control of the entire cardiovascular
      system is being discussed.

PMID- 8994550
TI  - Bradykinin increases catecholamine release via B2 receptors.
AB  - The mechanism by which bradykinin induces catecholamine release from neural
      tissues was investigated in two experimental models of rat origin. The rat
      phaeochromocytoma cell line PC12 was used to identify the subtype of bradykinin
      receptors involved in the stimulation of noradrenaline secretion and to compare
      the effects of three different B2-antagonists. An increase of catecholamine
      release induced by bradykinin in vivo could be confirmed by measuring plasma
      levels in pithed spontaneously hypertensive rats (SHR) during electric
      preganglionic stimulation of the spinal cord. In this whole animal model, the
      effects of inhibition of both uptake and alpha 2-adrenoceptors on plasma levels
      of noradrenaline and adrenaline were studied as well as the potentiation of
      exogenous bradykinin by inhibition of angiotensin I-converting enzyme and neutral
      endopeptidase. The receptor subtypes involved (i.e. B1 or B2) were characterized
      by application either of HOE 140 or desArg9-[Leu8]-bradykinin respectively. In
      PC12 cells bradykinin provoked a prominent increase of noradrenaline release at
      low concentrations (concentration required for 50% of the maximum response 1 nM),
      whereas the B1-agonist desArg9-bradykinin was only effective at concentrations
      higher than 30 microM. The effects of both kinins could be blocked by the B2
      specific antagonist HOE 890307 which, like HOE 140, exerted no agonistic effect
      of its own. As has been shown in other neural cells, the B2-specific antagonist
      [Thi5,8, D-Phe7]-bradykinin only acted as a low-affinity agonist without any
      antagonistic effects. In experiments where the intention was to induce B1
      receptor expression either by angiotensin I-converting enzyme inhibition or
      lipopolysaccharide application, no alteration of the secretory response of PC12
      cells to bradykinin or desArg9-bradykinin could be shown. In pithed SHR, infusion
      of bradykinin (up to 1200 ng/min/kg) did not enhance stimulation-dependent
      release of noradrenaline or adrenaline. After pretreatment of the rats with
      ramipril bradykinin became effective and its effects were further potentiated by
      the concomitant application of phosphoramidon. B2-antagonism by HOE 140 abolished
      the bradykinin-induced release of noradrenaline and reduced the effect on plasma
      adrenaline. The B1-specific antagonist desArg9-[Leu8]-bradykinin was unable to
      diminish the stimulatory effects of bradykinin and instead brought about an
      increase of plasma adrenaline levels. In conclusion, bradykinin stimulates
      release of catecholamines from PC12 cells, peripheral sympathetic neurons and
      chromaffine cells by activation of ganglionic or presynaptic B2-receptors. The
      adrenal medulla and PC12 cells appear to be highly susceptible not only to
      stimulation by bradykinin, but also to non-specific stimulatory effects of
      certain kinin-antagonists.

PMID- 8994551
TI  - Interaction of nitric oxide with myogenic and adrenergic vasoconstrictor
      processes in the control of microcirculatory blood flow.
AB  - Since the early observations of Carl Ludwig that the sympathetic nervous system
      exerts a tonic influence on resistance vessels, many additional factors have been
      identified which control vascular tone. The active modulator role of endothelium
      derived nitric oxide (NO) in this process has emerged only in the last decade.
      The interaction of the local vasodilator, NO, with systemic alpha-adrenergic
      control of vascular tone as well as with pressure-induced myogenic
      vasoconstriction is briefly reviewed in the present paper. Cellular mechanisms of
      this interaction are discussed. In vitro and in vivo experiments indicate that
      the continuous basal release of NO potently attenuates alpha-adrenergic and
      myogenic tone in resistance vessels by several independent mechanisms and that
      endothelial impairment results in abnormal vasoconstriction.

PMID- 8994552
TI  - The theory of and experimentation into respiratory gas exchange--Carl Ludwig and
      his school.
AB  - Investigations of respiratory functions progressed considerably in the middle of
      the 19th century. Motive forces for this were the improvement of basic medical
      sciences due to the progress in science politics, the evolution of exact
      measuring methods owing to the improvement of natural sciences and the origin of
      the ideology of antivitalism and organic physics, revealed by the striving of
      their leading scientists including Carl Ludwig. Formerly, exchange of O2 and CO2
      was related merely to the lungs without exact knowledge of data or mechanisms.
      Ludwig and his pupils improved the analytical methods of G. Magnus and L. Meyer
      and applied various experimental conditions thus obtaining data allowing the
      interpretation of the respiratory gas exchange in the organism according to
      physical laws. It was found that respiratory gases are transported in a
      chemically bound state; that the binding mechanisms for O2 and CO2 interact; that
      body tissues extract O2 and release CO2 depending on metabolism, and that partial
      pressures justify purely physical theories of the gas exchange. These results
      enabled the investigation of the transporting substance, haemoglobin, by F. Hoppe
      Seyler and of the binding and dissociation dynamics by C. Bohr, J.S. Haldane and
      A. and M. Krogh. Thus Ludwig bridged the gap from qualitative gas analysis to
      quantitative research into the kinetics of gas binding.

PMID- 8994553
TI  - Breathing--homeostatic function and voluntary motor activity.
AB  - In a magnitude production test, subjects of both sexes rated their breath depth
      under different conditions. In the first group, 50 subjects were examined at rest
      in the supine position and breathing spontaneously or assisted by a respirator.
      The second group, consisting of 33 subjects, was tested in the sitting position
      at rest and during mild bicycle exercise (females 35 W, males 40 W). Subjectively
      quantified breath depths and corresponding tidal volumes were compared and their
      relations were described by Stevens power function. The assessment of breath
      depth in spontaneous breathing at rest was remarkably precise (mean Stevens
      exponent 0.94 +/- 0.02). During assisted ventilation, rating was less accurate
      and tended to underestimate breath depth. Noticeable under both conditions was a
      tendency to overestimate voluntary tidal volume reductions. This was more
      pronounced in young (up to 35 years) women than in men or elderly women. During
      exercise, the subjects (men and women) overestimated both increases and
      reductions of tidal volume. Each voluntary tidal volume modification was
      accompanied immediately by involuntary changes of inspiration and expiration
      times, thus, partially compensating disturbances of ventilation. In addition,
      voluntarily reduced tidal volumes were quantitatively compensated within the
      first breath subsequent to the voluntary manoeuver. We conclude that breath depth
      sensation is more strongly related to proprioceptive signals than to
      visceroceptive signals and is influenced by the autonomous respiratory drive.
      Furthermore, proprioception is assumed to participate in the control of the
      autonomous respiratory drive.

PMID- 8994554
TI  - [Royal Belgian Societies of Oto-Rhino-Laryngology memorial issue 1890-1980].

PMID- 8994555
TI  - Urethral injuries revisited.

PMID- 8994556
TI  - Pre-operative analgesia after injury.
AB  - Much has been written on postoperative analgesia in the surgical patient.
      However, no work has been published on pre-operative pain relief in acute injury.
      We have studied 100 consecutive admissions, reviewing the prescribing pattern and
      administration of analgesia following acute injury in the period prior to
      operation, or the first 24 h as an in-patient. We found an over-reliance on a
      narrow range of analgesics to the exclusion of others. The choice and variety of
      analgesic offered, their frequency and route of administration could all have
      been improved. Equally, little thought was given to adjuvant forms of analgesic
      therapy which are well suited to the injured patient. Analgesics were prescribed
      more often than they were given. No pharmacological analgesia was prescribed in 9
      per cent of admissions, and a further 14 per cent were given no analgesia despite
      its being prescribed, i.e. 23 per cent of acutely injured patients received no
      analgesia during the pre-operative period, or first 24 h after admission. This
      audit revealed evidence of inadequate pre-operative analgesic prescribing and
      administration practices. We conclude that there is no place for complacency when
      managing the analgesic requirements of injured patients.

PMID- 8994557
TI  - Predictive value of the hip flexion test for fractures of the pelvis.
AB  - In 39 patients with pelvic injury, four clinical tests were performed during
      physical examination. Of these four tests, the positive and negative hip flexion
      test (active flexion of the hip with extension of the knee) had the highest
      predictive value for the presence (95 per cent) or the absence of pelvic
      fractures (90 per cent), respectively. The predictive values of the other three
      tests (downward compression on the pubic bone, compression on the iliac rings,
      and distraction pressure on the iliac crests) were considerably lower.

PMID- 8994558
TI  - Plate osteosynthesis of diaphyseal fractures of the radius and ulna.
AB  - Between January 1980 and December 1989, 133 consecutive patients were treated for
      a fracture of the shaft of one or both forearm bones (134 forearms in total). All
      fractures were stabilized with AO/ASIF 3.5 mm stainless-steel dynamic compression
      plates. The 1 year follow-up rate was 99 per cent; the long-term follow-up rate
      was 92 per cent (the mean long-term follow-up was 10.2 years (range, 2.7-15.2))
      so there were 96 men and 35 women, with an average age of 37.5 years (range, 16
      63). Twenty-two per cent of the forearms had open fractures, 26 per cent of
      patients had sustained multiple injuries and 19 per cent had a head injury. One
      hundred and twenty-seven of 132 forearms (96.2 per cent) underwent problem-free
      consolidation before 6 months. Two delayed unions and two non-unions required
      reoperation. There was one superficial infection in a patient with a closed
      fracture. Plates were removed from 70 patients (53 per cent) at a mean of 33.1
      months (range, 8-122) after the first operation. In this group, there were three
      refractures (4.3 per cent) occurring at a mean of 8.7 months (range, 0-14) after
      plate removal. This study confirms the safety and efficacy of plate
      osteosynthesis in forearm shaft fractures: a high union rate and low complication
      rate can be anticipated. The data presented form the most reliable information on
      this subject currently available with the longest and highest rate of follow up
      of a sufficient number of patients using a single implant system in a single
      institution.

PMID- 8994559
TI  - A study of patient-related characteristics and outcome after moderate injury.
AB  - The purpose of all injury care is to restore patients' pre-injury functioning and
      to facilitate the return to normal activities. The aim of this prospective study
      was to describe and analyse psychiatric factors and other patient-related
      characteristics which influence long-term results after moderate injuries. One
      hundred and sixty-nine injured patients were randomized to go through a
      comprehensive psychosocial research protocol and to participate in the 12 month
      follow up. The 49 patients lost to follow-up differed significantly from all
      other patients. They were more often single, blue-collar workers with a lower
      educational level and had a less favourable psychosocial background, including
      alcohol abuse. The 120 patients who completed the follow-up were divided in two
      groups: the non-recovered group (NR, N = 58), patients reporting limitations in
      performing their work and/or limitations in carrying out housework and/or in
      social life, and the recovered group (R, N = 62), patients reporting full
      recovery or only minor limitations in exercise or sports 12 months after the
      injury. The NR patients were older (P < 0.05), had a slightly higher injury
      Severity Score (P < 0.01) and showed signs of depression both during the acute
      post-injury period and at 1 year follow up (P < 0.001). The multivariate analysis
      showed that measurements of pain and depression during the acute post-injury
      period were associated with the functional outcome after 12 months. Co-operation
      between injury and psychiatric units should be developed to identify patients
      needing psychosocial or psychiatric support during the early phase of
      rehabilitation.

PMID- 8994560
TI  - War injuries of the kidney.
AB  - Between 2 May 1991 and 2 November 1992, 4425 wounded people were treated at the
      Clinical Hospital of Osijek, Croatia. A hundred and fifteen (2.6 per cent) had a
      urogenital injury, 64 (56 per cent) of whom had penetrating kidney injuries.
      Sixteen (25 per cent) of this 64 were caused by gunshot wounds and 48 (75 per
      cent) by fragments of mines, mortars or grenades. The majority of the 64 kidney
      injuries had also associated injuries of some other major organ system,
      particularly in the abdomen, with only three cases of isolated kidney injury. In
      53 patients (82.8 per cent) surgical access was by transabdominal incision, in
      nine (14 per cent) by extraperitoneal flank incision and in two cases
      thoracophrenolaparotomy was also performed. Nephrectomy was performed in 16
      patients (25 per cent). In 46 (75 per cent) an organ-sparing procedure was done:
      kidney sutures in 28 (43.8 per cent), kidney resection in five (7.8 per cent) and
      exploration only in 15 (23.4 per cent). Intrahospital deaths occurred in 11 (18
      per cent), seven in the operating theatre. An evaluation of the 6-month follow up
      for 90 per cent of the surviving patients is presented. It seems that the
      frequency of renal war injuries was lower than usually reported. Associated
      abdominal injuries justified surgical access by transabdominal incision. The high
      mortality rate is explained by a large number of associated injuries and by the
      proximity of the battlefield with resulting rapid transport of patients (average
      52 min), which excluded the possibility of separating out the moribund patients.
      Long-term follow up confirmed the benefits of the conserving surgical approach.

PMID- 8994561
TI  - The strength of iliosacral lag screws and transiliac bars in the fixation of
      vertically unstable pelvic injuries with sacral fractures.
AB  - This study compares the relative strengths of iliosacral lag screws and
      transiliac bars in the fixation of vertically unstable pelvic injuries with
      sacral fractures. A vertical sacral fracture was artificially induced by vertical
      loading in eight pelvises from cadavers, which were then fixed with two 6.5 mm
      iliosacral lag screws or two 6.4 mm transiliac bars. The pelvises were then
      loaded again to failure. The mean strength of iliosacral lag screw fixation was
      819 newtons and for transiliac bars it was 1066 newtons, but the study was too
      small for the difference to be judged as statistically significant. Various
      advantages and disadvantages of each method of fixation are discussed.

PMID- 8994562
TI  - Early mortality after cervical hip fractures.
AB  - A total of 59 (13.5 per cent) of 437 patients with cervical hip fractures died
      within the first 3 months, compared with an expected mortality rate of 2.6 per
      cent in the comparable general population (P < 0.05). The average age at death
      was 86 years (range, 62-98). The 3-months mortality rate among patients admitted
      from institutions was 24/105 = 23 per cent compared with 35/332 = 10.5 per cent
      for patients admitted from their own homes (P < 0.05). The 3-months mortality
      rate for patients with Garden 1 + 2 fractures was 9.4 per cent compared with 14
      per cent for Garden 3 + 4 (P < 0.05). This series seems to suggest that non
      cemented hemi-arthroplasty may be associated with an increased 3-months mortality
      rate of 21 per cent compared with 13.9 per cent (P < 0.05) for patients with the
      same age distribution. This may be due to a relatively high deep-infection rate
      following non-cemented hemi-arthroplasty.

PMID- 8994563
TI  - Intercondylar fractures of the distal humerus in adults.
AB  - Intercondylar fractures of the distal humerus in adults are difficult fractures
      to treat because of their rarity and associated significant comminution. The
      results of managing these fractures non-operatively are limited by failure to get
      anatomical reduction and early mobilization, which often results in painful stiff
      elbow and/or pseudarthrosis. Hence an operative management with anatomical
      reduction of the fragments becomes the treatment of choice for these fractures.
      The experience of managing 20 such fractures by open reduction and internal
      fixation with early mobilization is presented. Nineteen of these fractures
      attained acceptable results, 15 of which were graded as excellent in the final
      outcome. This study attempts to rationalize the operative management of these
      fractures regarding choice of surgical approach, choice of implants and timing of
      mobilization of elbow.

PMID- 8994564
TI  - Multiple non-contiguous injuries of the spine.
AB  - Forty-seven patients with multiple non-contiguous injuries of the spine were
      reviewed retrospectively, giving an incidence of 5.4 per cent of 875 spinal
      injuries. Thirty-three were men and 14 women with an age range of between 16 and
      78 years. Twenty-three were treated operatively. The multiple non-contiguous
      injuries had a more complicated mechanism of injury and tended to be more severe
      injuries than single-level injuries as they were combined more frequently with
      injuries of other parts of the body. Being aware of this combination of injuries
      leads to an earlier diagnosis. Operative reconstruction is recommended.

PMID- 8994565
TI  - Accurate anatomical location of war injuries: analysis of the Lebanon war fatal
      casualties and the proposition of new principles for the design of military
      personal armour system.
AB  - In this study we present a new approach to the design of the military personal
      armour system (MPAS). This approach is based on a computerized analysis of the
      exact anatomical location of 405 penetrating war injuries (290 shrapnel and 115
      bullet injuries) in 164 soldiers killed in the Lebanon war. All the penetrating
      injuries (hits) were plotted on a computerized image of the human body. About 90
      per cent of all hits were to the front of the body; 55 per cent of all hits were
      to the left side. About 45 per cent of all hits were to the torso, which is
      slightly more than the torso's proportion of total body-surface area (36 per
      cent). Of all hits to the torso, 64 per cent of the shrapnel hits and 73.3 per
      cent of the bullet hits were limited to the front mid torso (T4 to T9). The head
      at the level of the helmet received 9 per cent of all hits, most of which were
      over the frontal bones (72.4 per cent). The body part with the greatest density
      of penetrating injuries was the face, with 22.2 per cent of all penetrating
      wounds, and in particular the mid face, from the level of the lips to the level
      of the zygomatic bones, was especially vulnerable, sustaining 10 per cent of all
      the penetrating wounds. These findings suggest several possible modifications in
      the standard MPAS: an additional protective device over the front mid torso may
      be incorporated; the face may be protected by a transparent and lightweight face
      shield; a horizontal margin added to the standard helmet may protect the upper
      face from missiles from above; a chin cover may protect the lower face.

PMID- 8994566
TI  - Non-operative or operative treatment for undisplaced femoral neck fractures: a
      comparative study of 122 non-operative and 125 operatively treated cases.
AB  - We present a series of 247 undisplaced femoral neck fractures, of which 122 were
      primarily treated non-operatively, and 125 with primary operative stabilization.
      The background parameters did not differ significantly in the two groups. The
      length of hospitalization was 1 week shorter in the operatively treated group.
      They started to walk bearing full weight at an average of 11 days earlier. Two
      thirds of the operatively treated but only one-quarter of the non-operatively
      treated patients were able to walk alone when they left hospital. General
      complications were recorded in 19 of the non-operatively and in four of the
      operatively treated patients during their hospitalization. Early displacement
      (within 6 weeks) was noted in 20 per cent of the non-operatively treated patients
      who required late operation. However, there was no early displacement in the
      operatively treated group. We therefore recommend primary operative stabilization
      of undisplaced femoral neck fractures.

PMID- 8994567
TI  - Multiple impalement injury--a remarkable survival.

PMID- 8994568
TI  - Split fracture of the proximal phalanx of thumb--an unusual cricket injury.

PMID- 8994569
TI  - Breakage of Mennen femur device.

PMID- 8994570
TI  - Traumatic intervertebral incarceration of ileum: a unique lap belt injury.

PMID- 8994571
TI  - Bilateral 'Jones' fractures of the fifth metatarsal following relapse of talipes
      equinovarus.

PMID- 8994576
TI  - The AII amacrine network: coupling can increase correlated activity.
AB  - Retinal ganglion cells in the cat respond to single rhodopsin isomerizations with
      one to three spikes. This quantal signal is transmitted in the retina by the rod
      bipolar pathway: rod-->rod bipolar-->AII-->cone bipolar-->ganglion cell. The two
      dimensional circuit underlying this pathway includes extensive convergence from
      rods to an AII amacrine cell, divergence from a rod to several AII and ganglion
      cells, and coupling between the AII amacrine cells. In this study we explored the
      function of coupling by reconstructing several AII amacrine cells and the gap
      junctions between them from electron micrographs; and simulating the AII network
      with and without coupling. The simulation showed that coupling in the AII network
      can: (1) improve the signal/noise ratio in the AII network; (2) improve the
      signal/noise ratio for a single rhodopsin isomerization striking in the periphery
      of the ganglion cell receptive field center, and therefore in most ganglion cells
      responding to a single isomerization; (3) expand the AII and ganglion cells'
      receptive field center; and (4) expand the "correlation field". All of these
      effects have one major outcome: an increase in correlation between ganglion cell
      activity. Well correlated activity between the ganglion cells could improve the
      brain's ability to discriminate few absorbed external photons from the high
      background of spontaneous thermal isomerizations. Based on the possible benefits
      of coupling in the AII network, we suggest that coupling occurs at low scotopic
      luminances.

PMID- 8994577
TI  - What is the denominator for contrast normalisation?
AB  - The perceived speed of 1 c/deg sinusoidal gratings of contrast 0.02 was measured
      in the presence of high contrast (0.50) 1 c/deg sinusoidal gratings (called
      modifiers). The modifiers drifted or were counterphase modulated at various
      temporal frequencies. The presence of a modifier with temporal frequencies (0 and
      3 Hz) lower than the low contrast moving grating decreased its perceived speed
      while the presence of modifiers with higher temporal frequencies (8, 12 and 16
      Hz) increased its perceived speed. A modifier of the same temporal frequency (6
      Hz) as the standard grating had no effect upon the perceived speed of the low
      contrast gratings. Moving modifiers are more effective than counterphase
      flickering modifiers in biasing the perceived speed of low contrast gratings if
      they move in the same direction as the test grating and less effective if they
      move in the opposite direction. Finally, a modifier presented in an annulus
      surrounding the test grating is more effective than a modifier presented in a
      circular patch above or below the test grating in raising the perceived speed of
      low contrast gratings. This suggests that perceived speed depends on the ratio of
      low and high temporal frequency signals averaged over a significant area of the
      visual field.

PMID- 8994578
TI  - Flicker sensitivity as a function of spectral density of external white temporal
      noise.
AB  - Foveal flicker sensitivity at 0.5-30 Hz was measured as a function of the
      spectral density of external, white, purely temporal noise for a sharp-edged 2.5
      deg circular spot (mean luminance 3.4 log phot td). Sensitivity at any given
      temporal frequency was constant at low powers of external noise, but then
      decreased in inverse proportion to the square root of noise spectral density.
      Without external noise, sensitivity as function of temporal frequency had the
      well-known band-pass characteristics peaking at about 10 Hz, as previously
      documented in a large number of studies. In the presence of strong external
      noise, however, sensitivity was a monotonically decreasing function of temporal
      frequency. Our data are well described (goodness of fit 90%) by a model
      comprising (i) low-pass filtering by retinal cones, (ii) high-pass filtering in
      the subsequent neural pathways, (iii) adding of the temporal equivalent of
      internal white spatiotemporal noise, and (iv) detection by a temporal matched
      filter, the efficiency of which decreases approximately as the power -0.58 of
      temporal frequency.

PMID- 8994579
TI  - Precise assessment of the mean effective luminance of texture patches--an
      approach based on reverse-phi motion.
AB  - In studying the response of mechanisms to contrast-defined texture stimuli, it is
      critical that the average effective luminance of these textures be equal to that
      of the background, to minimize net luminance-based signals. We present an
      efficient and accurate technique for constructing such equiluminant textures to
      isolate contrast-sensitive mechanisms for investigating their properties. The
      technique is based on the reverse-phi motion phenomenon, and the resulting
      settings agree closely with those obtained by photometric means for the class of
      textures studied. The method also allows one to explore the properties of
      contrast- and luminance-driven motion mechanisms and, in particular, to evaluate
      the contribution of putative second-order mechanisms to the motion percept.
      Results of applying the method are presented, and its advantages over the minimum
      flicker and minimum-motion techniques are discussed.

PMID- 8994580
TI  - Localization of a peripheral patch: the role of blur and spatial frequency.
AB  - Peripheral vision serves to direct our attention and fixation to objects of
      interest. This requires that the visual system be capable of accurately
      localizing peripherally presented targets having different spatial structures.
      The question we address is "to what extent does stimulus spatial structure
      influence the precision of peripheral localization?" To address this issue, we
      measured the precision of spatial localization (with reference to a foveal
      target) for a single Gaussian or Gabor patch briefly presented in the periphery.
      For both stimuli, we find that when the standard deviation of the stimulus
      envelope (SD) is less than 1/5 the stimulus eccentricity, localization thresholds
      are independent of SD and are approximately 1/50 of eccentricity. For larger
      values of SD, localization thresholds increase linearly with increasing SD, and
      are approximately 1/5 of SD. The results hold over a range of eccentricities
      (from 2.5 to 10 deg) and stimulus contrasts (from near detection threshold to
      80%). In addition, for Gabor patches, the results are independent of frequency,
      phase and orientation of the carrier.

PMID- 8994581
TI  - The special role of distant structures in perceived object velocity.
AB  - How do we judge an object's velocity when we ourselves are moving? Subjects
      compared the velocity of a moving object before and during simulated ego-motion.
      The simulation consisted of moving the visible environment relative to the
      subject's eye in precisely the way that a static environment would move relative
      to the eye if the subject had moved. The ensuing motion of the background on the
      screen influenced the perceived target velocity. We found that the motion of the
      "most distant structure" largely determined the influence of the moving
      background. Relying on retinal motion relative to that of distant structures is
      usually a reliable method for accounting for rotations of the eye. It provides an
      estimate of the object's movement, relative to the observer. This strategy for
      judging object motion has the advantage that it does not require metric
      information on depth or detailed knowledge of one's own motion.

PMID- 8994582
TI  - Depth asymmetry in da Vinci stereopsis.
AB  - We investigated processes that determine the depth localization of monocular
      points which have no unambiguous depth. It is known that horizontally adjacent
      binocular objects are used in depth localization and for a distance of 25-40 min
      arc monocular points localize to the leading edge of a depth constraint zone,
      which is an area defined by the visibility lines between which the points in the
      real world must be. We demonstrate that this rule is not valid in complex depth
      scenes. Adding other disparate objects to the scene changes the localization of
      the monocular point in a way that cannot be explained by the da Vinci explanation
      of monocular-binocular integration. The effect of additional disparate objects is
      asymmetric in depth: a crossed object does not affect the da Vinci effect but an
      uncrossed object biases the depth localization of monocular objects to uncrossed
      direction. We conclude that a horizontally adjacent binocular plane does not
      completely determine the depth localization of a monocular point and that depth
      spreading from other binocular elements biases the localization process.

PMID- 8994583
TI  - Primitives used in the spatial localization of nonabutting stimuli: peaks or
      centroids.
AB  - In order to determine whether simple luminance profiles are located by their
      peaks or centroids we performed a three element alignment task where the central
      element's degree of luminance asymmetry was randomly chosen from a flat
      distribution (skew noise). The central element with its randomly chosen skew was
      either positioned using the peak or centroid of its distribution. Accuracy is
      invariant with the magnitude of the skew noise for the centroid but not the peak
      condition. We conclude that the human visual system assigns position tags using
      centroids not peaks of luminance distributions for gabors. However this is not
      the case for Gaussian blobs, where a measure closer to the midpoint is used for
      our stimulus arrangement.

PMID- 8994584
TI  - Stability of binocular depth perception with moving head and eyes.
AB  - We systematically analyse the binocular disparity field under various eye, head
      and stimulus positions and orientations. From the literature we know that certain
      classes of disparity which involve the entire disparity field (such as those
      caused by horizontal lateral shift, differential rotation, horizontal scale and
      horizontal shear between the entire half-images of a stereogram) lead to
      relatively poor depth perception in the case of limited observation periods.
      These classes of disparity are found to be similar to the classes of disparities
      which are brought about by eye and head movements. Our analysis supports the
      suggestion that binocular depth perception is based primarily (for the first few
      hundred milliseconds) on classes of disparity that do not change as a result of
      ego-movement.

PMID- 8994585
TI  - Bradykinin receptor inhibition affects the rod b-wave in the cat
      electroretinogram.
AB  - In 10 anaesthetized cats, electroretinographic (ERG) measurements were carried
      out to further elucidate the involvement of bradykinin as a substrate component
      of the renin-angiotensin system in retinal neurotransmission. Reducing
      angiotensin II concentration by angiotensin-converting enzyme (ACE) inhibition
      increased sensitivity (0.5 log units) and gain (50%) of the rod b-wave amplitude.
      The b-wave implicit time was decreased only at high stimulus intensities (> 10(
      2) cd/m). Blocking bradykinin receptors specifically decreased rod b-wave
      implicit time for all intensities, while its amplitude remained unaffected.
      Bradykinin effects were independent of alterations of angiotensin II activity. We
      therefore suggest that bradykinin influences inner retinal signal processing,
      hereby further supporting the hypothesis of a renin-angiotensin system
      involvement in retinal neurotransmission.

PMID- 8994586
TI  - The comparative development of movement hyperacuity and visual acuity in
      children.
AB  - Oscillatory movement displacement thresholds (OMDT) have been suggested as a test
      of neural integrity of the visual system, detecting deficit even in the presence
      of normal resolution. Both OMDT and visual resolution were measured in 153 normal
      children between the ages of 2.2 and 13 yr (mean = 6.2 +/- 2.8 yr). OMDT were
      obtained using a computer-generated vertical bar stimulus oscillating at 4 Hz.
      Visual acuity was determined using a Polymetric Vision Assessment technique (PVA)
      where a single letter optotype is presented at increasing viewing distance to
      determine threshold. OMDT is a hyperacuity at all ages, exhibiting improving
      thresholds up to around 8 yr of age when results are typical of adults. PVA
      thresholds improve less markedly over the range measured, appearing mature by 6-7
      yr. Correlation between OMDT hyperacuity and visual acuity is poor, illustrating
      the complexity of the relationship between hyperacuity and resolution functions.

PMID- 8994587
TI  - Definite answers from random events.

PMID- 8994588
TI  - Classical molecular dynamics simulation of the photoinduced electron transfer
      dynamics of plastocyanin.
AB  - Classical molecular dynamics simulations are used to investigate the nuclear
      motions associated with photoinduced electron transfer in plastocyanin. The blue
      copper protein is modeled using a molecular mechanics potential; potential
      parameters for the copper-protein interactions are determined using an x-ray
      crystallographic structure and absorption and resonance Raman spectra. Molecular
      dynamics simulations yield a variety of information about the ground (oxidized)
      and optically excited (charge-transfer) states: 1) The probability distribution
      of the potential difference between the states, which is used to determine the
      coordinate and energy displacements, places the states well within the Marcus
      inverted region. 2) The two-time autocorrelation function of the difference
      potential in the ground state and the average of the difference potential after
      instantaneous excitation to the excited state are very similar (confirming linear
      response in this system); their decay indicates that vibrational relaxation
      occurs in about 1 ps in both states. 3) The spectral densities of various
      internal coordinates begin to identify the vibrations that affect the optical
      transition; the spectral density of the difference potential correlation function
      should also prove useful in quantum simulations of the back electron transfer. 4)
      Correlation functions of the protein atomic motions with the difference potential
      show that the nuclear motions are correlated over a distance of more than 20 A,
      especially along proposed electron transport paths.

PMID- 8994589
TI  - Coupling of protein surface hydrophobicity change to ATP hydrolysis by myosin
      motor domain.
AB  - Dielectric spectroscopy with microwaves in the frequency range between 0.2 and 20
      GHz was used to study the hydration of myosin subfragment 1 (S1). The data were
      analyzed by a method recently devised, which can resolve the total amount of
      water restrained by proteins into two components, one with a rotational
      relaxation frequency (fc) in the gigahertz region (weakly restrained water) and
      the other with lower fc (strongly restrained water). The weight ratio of total
      restrained water to S1 protein thus obtained (0.35), equivalent to 2100 water
      molecules per S1 molecule, is not much different from the values (0.3-0.4) for
      other proteins. The weakly restrained component accounts for about two-thirds of
      the total restrained water, which is in accord with the number of water molecules
      estimated from the solvent-accessible surface area of alkyl groups on the surface
      of the atomic model of S1. The number of strongly restrained water molecules
      coincides with the number of solvent-accessible charged or polar atoms. The
      dynamic behavior of the S1-restrained water during the ATP hydrolysis was also
      examined in a time-resolved mode. The result indicates that when S1 changes from
      the S1.ADP state into the S1.ADP.P1 state (ADP release followed by ATP binding
      and cleavage), about 9% of the weakly restrained waters are released, which are
      restrained again on slow P1 release. By contrast, there is no net mobilization of
      strongly restrained component. The observed changes in S1 hydration are
      quantitatively consistent with the accompanying large entropy and heat capacity
      changes estimated by calorimetry (Kodama, 1985), indicating that the protein
      surface hydrophobicity change plays a crucial role in the enthalpy-entropy
      compensation effects observed in the steps of S1 ATP hydrolysis.

PMID- 8994590
TI  - Ultrafast absorption difference spectra of the Fenna-Matthews-Olson protein at 19
      K: experiment and simulations.
AB  - We describe simulations of absorption difference spectra in strongly coupled
      photosynthetic antennas. In the presence of large resonance couplings,
      distinctive features arise from excited-state absorption transitions between one-
      and two-exciton levels. We first outline the theory for the heterodimer and for
      the general N-pigment system, and we demonstrate the transition between the
      strong and weak coupling regimes. The theory is applied to Fenna-Matthews-Olson
      (FMO) bacteriochlorophyll a protein trimers from the green photosynthetic
      bacterium Prosthecochloris aestuarii and then compared with experimental low
      temperature absorption difference spectra of FMO trimers from the green bacterium
      Chlorobium tepidum.

PMID- 8994591
TI  - Changes in the spectral properties of a plasma membrane lipid analog during the
      first seconds of endocytosis in living cells.
AB  - N-[5-(5, 7-dimethyl Bodipy)-1-pentanoyl]-D-erythro-sphingosylphosphorylcholine
      (C5-DMB-SM), a fluorescent analog of sphingomyelin, has been used in a study of
      the formation of very early endosomes in human skin fibroblasts. This lipid
      exhibits a shift in its fluorescence emission maximum from green (approximately
      515 nm) to red (approximately 620 nm) wavelengths with increasing concentrations
      in membranes. When cells were incubated with 5 microM C5-DMB-SM at 4 degrees C
      and washed, only plasma membrane fluorescence (yellow-green) was observed. When
      these cells were briefly (< or = 1 min) warmed to 37 degrees C to allow
      internalization to occur, and then incubated with defatted bovine serum albumin
      (back-exchanged) at 11 degrees C to remove fluorescent lipids from the plasma
      membrane, C5-DMB-SM was distributed in a punctate pattern throughout the
      cytoplasm. Interestingly, within the same cell some endosomes exhibited green
      fluorescence, whereas others emitted red-orange fluorescence. Furthermore, the
      red-orange endosomes were usually seen at the periphery of the cell, while the
      green endosomes were more uniformly distributed throughout the cytoplasm. This
      mixed population of endosomes was seen after internalization times as short as 7
      s and was also seen over a wide range of C5-DMB-SM concentrations (1-25 microM).
      Control experiments established that the variously colored endosomes were not
      induced by changes in pH, membrane potential, vesicle size, or temperature.
      Quantitative fluorescence microscopy demonstrated that the apparent concentration
      of the lipid analog in the red-orange endosomes was severalfold higher than its
      initial concentration at the plasma membrane, suggesting selective
      internalization (sorting) of the lipid into a subset of early endosomes.
      Colocalization studies using C5-DMB-SM and either anti-transferrin receptor
      antibodies or fluorescently labeled low-density lipoprotein further demonstrated
      that this subpopulation of endosomes resulted from receptor-mediated endocytosis.
      We conclude that the spectral properties of C5-DMB-SM can be used to distinguish
      unique populations of early endosomes from one another and to record dynamic
      changes in their number and distribution within living cells.

PMID- 8994592
TI  - A model for the kinetics of homotypic cellular aggregation under static
      conditions.
AB  - We present the formulation and testing of a mathematical model for the kinetics
      of homotypic cellular aggregation. The model considers cellular aggregation under
      no-flow conditions as a two-step process. Individual cells and cell aggregates 1)
      move on the tissue culture surface and 2) collide with other cells (or
      aggregates). These collisions lead to the formation of intercellular bonds. The
      aggregation kinetics are described by a system of coupled, nonlinear ordinary
      differential equations, and the collision frequency kernel is derived by
      extending Smoluchowski's colloidal flocculation theory to cell migration and
      aggregation on a two-dimensional surface. Our results indicate that aggregation
      rates strongly depend upon the motility of cells and cell aggregates, the
      frequency of cell-cell collisions, and the strength of intercellular bonds. Model
      predictions agree well with data from homotypic lymphocyte aggregation
      experiments using Jurkat cells activated by 33B6, an antibody to the beta 1
      integrin. Since cell migration speeds and all the other model parameters can be
      independently measured, the aggregation model provides a quantitative methodology
      by which we can accurately evaluate the adhesivity and aggregation behavior of
      cells.

PMID- 8994593
TI  - Charge density-dependent strength of hydration and biological structure.
AB  - Small ions of high charge density (kosmotropes) bind water molecules strongly,
      whereas large monovalent ions of low charge density (chaotropes) bind water
      molecules weakly relative to the strength of water-water interactions in bulk
      solution. The standard heat of solution of a crystalline alkali halide is shown
      here to be negative (exothermic) only when one ion is a kosmotrope and the ion of
      opposite charge is a chaotrope; this standard heat of solution is known to become
      proportionally more positive as the difference between the absolute heats of
      hydration of the corresponding gaseous anion and cation decreases. This suggests
      that inner sphere ion pairs are preferentially formed between oppositely charged
      ions with matching absolute enthalpies of hydration, and that biological
      organization arises from the noncovalent association of moieties with matching
      absolute free energies of solution, except where free energy is expended to keep
      them apart. The major intracellular anions (phosphates and carboxylates) are
      kosmotropes, whereas the major intracellular monovalent cations (K+; arg, his,
      and lys side chains) are chaotropes; together they form highly soluble, solvent
      separated ion pairs that keep the contents of the cell in solution.

PMID- 8994594
TI  - External barium influences the gating charge movement of Shaker potassium
      channels.
AB  - External Ba2+ speeds the OFF gating currents (IgOFF) of Shaker K+ channels but
      only upon repolarization from potentials that are expected to open the channel
      pore. To study this effect we used a nonconducting and noninactivating mutant of
      the Shaker K+ channel, ShH4-IR (W434F). External Ba2+ slightly decreases the
      quantity of ON gating charge (QON) upon depolarization to potentials near -30 mV
      but has little effect on the quantity of charge upon stepping to more
      hyperpolarized or depolarized potentials. More strikingly, Ba2+ significantly
      increases the decay rate of IgOFF upon repolarization to -90 mV from potentials
      positive to approximately -55 mV. For Ba2+ to have this effect, the depolarizing
      command must be maintained for a duration that is dependent on the depolarizing
      potential (> 4 ms at -30 mV and > 1 ms at 0 mV). The actions of Ba2+ on the
      gating current are dose-dependent (EC50 approximately 0.2 mM) and are not
      produced by either Ca2+ or Mg2+ (2 mM). The results suggest that Ba2+ binds to a
      specific site on the Shaker K+ channel that destabilizes the open conformation
      and thus facilitates the return of gating charge upon repolarization.

PMID- 8994595
TI  - The structure and organization of synthetic putative membranous segments of ROMK1
      channel in phospholipid membranes.
AB  - The hydropathy plot of ROMK1, an inwardly rectifying K+ channel, suggests that
      the channel contains two transmembrane domains (M1 and M2) and a linker between
      them with significant homology to the H5 pore region of voltage-gated K+
      channels. To gain structural information on the pore region of the ROMK1 channel,
      we used a spectrofluorimetric approach and characterized the structure, the
      organization state, and the ability of the putative membranous domains of the
      ROMK1 channel to self-assemble and coassemble within lipid membranes. Circular
      dichroism (CD) spectroscopy revealed that M1 and M2 adopt high alpha-helical
      structures in egg phosphatidylcholine small unilamellar vesicles and 40%
      trifluoroethanol (TFE)/water, whereas H5 is not alpha-helical in either egg
      phosphatidylcholine small unilamellar vesicles or 40% TFE/water. Binding
      experiments with 4-fluoro-7-nitrobenz-2-oxa-1,3-diazole (NBD)-labeled peptide
      demonstrated that all of the peptides bind to zwitterionic phospholipid membranes
      with partition coefficients on the order of 10(5) M-1. Tryptophan quenching
      experiments using brominated phospholipids revealed that M1 is dipped into the
      hydrophobic core of the membrane. Resonance energy transfer (RET) measurements
      between fluorescently labeled pairs of donor (NBD)/acceptor (rhodamine) peptides
      revealed that H5 and M2 can self-associate in their membrane-bound state, but M1
      cannot. Moreover, the membrane-associated nonhelical H5 serving as a donor can
      coassemble with the alpha-helical M2 but not with M1, and M1 can coassemble with
      M2. No coassembly was observed between any of the segments and a membrane
      embedded alpha-helical control peptide, pardaxin. The results are discussed in
      terms of their relevance to the proposed topology of the ROMK1 channel, and to
      general aspects of molecular recognition between membrane-bound polypeptides.

PMID- 8994596
TI  - Permeation through an open channel: Poisson-Nernst-Planck theory of a synthetic
      ionic channel.
AB  - The synthetic channel [acetyl-(LeuSerSerLeuLeuSerLeu)3-CONH2]6 (pore diameter
      approximately 8 A, length approximately 30 A) is a bundle of six alpha-helices
      with blocked termini. This simple channel has complex properties, which are
      difficult to explain, even qualitatively, by traditional theories: its single
      channel currents rectify in symmetrical solutions and its selectivity (defined by
      reversal potential) is a sensitive function of bathing solution. These complex
      properties can be fit quantitatively if the channel has fixed charge at its ends,
      forming a kind of macrodipole, bracketing a central charged region, and the
      shielding of the fixed charges is described by the Poisson-Nernst-Planck (PNP)
      equations. PNP fits current voltage relations measured in 15 solutions with an
      r.m.s. error of 3.6% using four adjustable parameters: the diffusion coefficients
      in the channel's pore DK = 2.1 x 10(-6) and DCl = 2.6 x 10(-7) cm2/s; and the
      fixed charge at the ends of the channel of +/- 0.12e (with unequal densities 0.71
      M = 0.021e/A on the N-side and -1.9 M = -0.058e/A on the C-side). The fixed
      charge in the central region is 0.31e (with density P2 = 0.47 M = 0.014e/A). In
      contrast to traditional theories, PNP computes the electric field in the open
      channel from all of the charges in the system, by a rapid and accurate numerical
      procedure. In essence, PNP is a theory of the shielding of fixed (i.e.,
      permanent) charge of the channel by mobile charge and by the ionic atmosphere in
      and near the channel's pore. The theory fits a wide range of data because the
      ionic contents and potential profile in the channel change significantly with
      experimental conditions, as they must, if the channel simultaneously satisfies
      the Poisson and Nernst-Planck equations and boundary conditions. Qualitatively
      speaking, the theory shows that small changes in the ionic atmosphere of the
      channel (i.e., shielding) make big changes in the potential profile and even
      bigger changes in flux, because potential is a sensitive function of charge and
      shielding, and flux is an exponential function of potential.

PMID- 8994597
TI  - Atomic distance estimates from disulfides and high-affinity metal-binding sites
      in a K+ channel pore.
AB  - The pore of potassium channels is lined by four identical, highly conserved
      hairpin loops, symmetrically arranged around a central permeation pathway.
      Introduction of cysteines into the external mouth of the drk1 K channel pore
      resulted in the formation of disulfide bonds that were incompatible with channel
      function. Breaking these bonds restored function and resulted in a high-affinity
      Cd(2+)-binding site, indicating coordinated ligation by multiple sulfhydryls.
      Dimeric constructs showed that these disulfide bonds formed between subunits.
      These results impose narrow constraints on intersubunit atomic distances in the
      pore that strongly support a radial pore model. The data also suggest an
      important functional role for the outer mouth of the pore in gating or
      permeation.

PMID- 8994598
TI  - Ion selectivity predictions from a two-site permeation model for the cyclic
      nucleotide-gated channel of retinal rod cells.
AB  - We developed a two-site, Eyring rate theory model of ionic permeation for cyclic
      nucleotide-gated channels (CNGCs). The parameters of the model were optimized by
      simultaneously fitting current-voltage (IV) data sets from excised photoreceptor
      patches in electrolyte solutions containing one or more of the following ions:
      Na+, Ca2+, Mg2+, and K+. The model accounted well for 1) the shape of the IV
      relations; 2) the binding affinity for Na+; 3) reversal potential values with
      single-sided additions of Ca2+ or Mg2+ and biionic KCl; and 4) the K1 and voltage
      dependence for divalent block from the cytoplasmic side of the channel. The
      differences between the predicted K1's for extracellular block by Ca2+ and Mg2+
      and the values obtained from heterologous expression of only the alpha-subunit of
      the channel suggest that the beta-subunit or a cell-specific factor affects the
      interaction of divalent cations at the external but not the internal face of the
      channel. The model predicts concentration-dependent permeability ratios with
      single-sided addition of Ca2+ and Mg2+ and anomalous mole fraction effects under
      a limited set of conditions for both monovalent and divalent cations. Ca2+ and
      Mg2+ are predicted to carry 21% and 10%, respectively, of the total current in
      the retinal rod cell at -60 mV.

PMID- 8994599
TI  - Anion, cation, and zwitterion selectivity of phospholemman channel molecules.
AB  - Phospholemman (PLM), a 72-amino acid membrane protein with a single transmembrane
      domain, forms taurine-selective ion channels in lipid bilayers. Because taurine
      forms zwitterions, a taurine-selective channel might have binding sites for both
      anions and cations. Here we show that PLM channels indeed allow fluxes of both
      cations and anions, making instantaneous and voltage-dependent transitions among
      conformations with drastically different ion selectivity characteristics. This
      surprising and novel ion channel behavior offers a molecular explanation for
      selective taurine flux across cell membranes and may explain why molecules in the
      phospholemman family can induce cation- or anion-selective conductances when
      expressed in Xenopus oocytes.

PMID- 8994601
TI  - K+ channel inactivation mediated by the concerted action of the cytoplasmic N-
      and C-terminal domains.
AB  - We have examined the molecular mechanism of rapid inactivation gating in a mouse
      Shal K+ channel (mKv4.1). The results showed that inactivation of these channels
      follows a complex time course that is well approximated by the sum of three
      exponential terms. Truncation of an amphipathic region at the N-terminus
      (residues 2-71) abolished the rapid phase of inactivation (r = 16 ms) and altered
      voltage-dependent gating. Surprisingly, these effects could be mimicked by
      deletions affecting the hydrophilic C-terminus. The sum of two exponential terms
      was sufficient to describe the inactivation of deletion mutants. In fact, the
      time constants corresponded closely to those of the intermediate and slow phases
      of inactivation observed with wild-type channels. Further analysis revealed that
      several basic amino acids at the N-terminus do not influence inactivation, but a
      positively charged domain at the C-terminus (amino acids 420-550) is necessary to
      support rapid inactivation. Thus, the amphipathic N-terminus and the hydrophilic
      C-terminus of mKv4.1 are essential determinants of inactivation gating and may
      interact with each other to maintain the N-terminal inactivation gate near the
      inner mouth of the channel. Furthermore, this inactivation gate may not behave
      like a simple open-channel blocker because channel blockade by internal
      tetraethylammonium was not associated with slower current decay and an elevated
      external K+ concentration retarded recovery from inactivation.

PMID- 8994600
TI  - Subconductance states in single-channel activity of skeletal muscle ryanodine
      receptors after removal of FKBP12.
AB  - FKBP12 was removed from ryanodine receptors (RyRs) by incubation of rabbit
      skeletal muscle terminal cisternae membranes with rapamycin. The extent of FKBP12
      removal was estimated by immunostaining Western blots of terminal cisternae
      proteins. Single FKBP12-depleted RyR channels, incorporated into planar lipid
      bilayers, were modulated by Ca2+, ATP, ryanodine, and ruthenium red in the cis
      chamber and opened frequently to the normal maximum conductance of approximately
      230 pS and to substate levels of approximately 0.25, approximately 0.5, and
      approximately 0.75 of the maximum conductance. Substate activity was rarely seen
      in native RyRs. Ryanodine did not after the number of conductance levels in
      FKBP12-depleted channels, but, at a membrane potential of +40 mV, reduced both
      the maximum and the substate conductances by approximately 50%. FKBP12-stripped
      channels were activated by a 10-fold-lower [Ca2+] and inhibited by a 10-fold
      higher [Ca2+], than RyRs from control-incubated and native terminal cisternae
      vesicles. The open probability (Po) of these FKBP12-deficient channels was
      greater than that of control channels at 0.1 microM and 1 mM cis Ca2+ but no
      different at 10 microM cis Ca2+, where channels showed maximal Ca2+ activation.
      The approximately 0.25 substate was less sensitive than the maximum conductance
      to inhibition by Ca2+ and was the dominant level in channels inhibited by 1 mM
      cis Ca2+. The results show that FKBP12 coordinates the gating of channel activity
      in control and ryanodine-modified RyRs.

PMID- 8994603
TI  - Ion conductance of the Ca(2+)-activated maxi-K+ channel from the embryonic rat
      brain.
AB  - By using single-channel recording techniques, we measured the conductance (gK) of
      the Ca(2+)-activated Maxi-K+ channel from the embryonic rat brain, and examined
      its dependence on K+ ions present in equimolar concentrations on both sides of
      the membrane patch. With ionic strength maintained constant by substitution of N
      methyl-D-glucamine for K+, gK has a sigmoidal dependence upon [K+]. This result
      has been obscured in previous work by variations in ionic strength, which has a
      marked effect on single-channel conductance, especially in the limit for which
      this variable approaches zero. The gK versus [K+] relationship is described,
      theoretically, by a three-barrier, two-binding-site model in which the barrier
      that an ion must cross to leave the channel is decreased as [K+] is increased.

PMID- 8994602
TI  - Modulation of L-type Ca2+ current by fast and slow Ca2+ buffering in guinea pig
      ventricular cardiomyocytes.
AB  - Free Ca2+ near Ca2+ channel pores is expected to be lower in cardiomyocytes
      dialyzed with bis-(o-amino-phenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA)
      than with ethyleneglycol-bis-(beta-aminoethyl)-N,N,N',N'-tetraacetic acid (EGTA)
      because BAPTA chelates incoming Ca2+ more rapidly. The consequences of
      intracellular Ca2+ buffering by BAPTA (0.2-60 mM) and by EGTA (0.2-67 mM) on
      whole-cell L-type Ca2+ current (ICa,L) were investigated in voltage-clamped
      guinea pig ventricular cardiomyocytes; bulk cytoplasmic free Ca2+ (Cac2+) was
      monitored using the fluorescent Ca2+ indicator indo-1. ICa,L was augmented by
      approximately 12-fold when BAPTA in the cell dialysate was increased from 0.2 to
      50 mM (half-maximal stimulation at 31 mM), whereas elevating internal EGTA from
      0.2 to 67 mM increased ICa,L only by approximately 2-fold. Cac2+ was < 20 nM with
      internal BAPTA or EGTA > or = 20 mM. While EGTA up to 67 mM had only an
      insignificant inhibitory effect on the stimulation of ICa,L by 3 microM
      forskolin, ICa,L in 50 mM BAPTA-dialyzed myocytes was insensitive to forskolin
      induced elevation of adenosine 3',5'-cyclic monophosphate (cAMP); conversely,
      ICa,L in cAMP-loaded cells was unresponsive to BAPTA dialysis. Cell dialysis with
      BAPTA, but not with EGTA, accelerated the slow component of ICa,L inactivation
      (tau S) without affecting its fast component (tau F), resembling the effects of
      cAMP-dependent phosphorylation. BAPTA-stimulated ICa,L was inhibited by
      acetylcholine and by the cAMP-dependent protein kinase (PKA) blocker H-89. These
      results suggest that BAPTA-induced lowering of peri-channel Ca2+ stimulates cAMP
      synthesis and channel phosphorylation by disinhibiting Ca(2+)-sensitive adenylyl
      cyclase.

PMID- 8994604
TI  - Potassium currents in presynaptic hair cells of Hermissenda.
AB  - Apart from their primary function as balance sensors, Hermissenda hair cells are
      presynaptic neurons involved in the Ca(2+)-dependent neuronal plasticity in
      postsynaptic B photoreceptors that accompanies classical conditioning. With a
      view to beginning to understand presynaptic mechanisms of plasticity in the
      vestibulo-visual system, a locus for conditioning-induced neuronal plasticity,
      outward currents that may govern the excitability of hair cells were recorded by
      means of a whole-cell patch-clamp technique. Three K+ currents were
      characterized: a 4-aminopyridine-sensitive transient outward K+ current (IA), a
      tetraethyl ammonium-sensitive delayed rectifier K+ current (IK,V), and a Ca(2+)
      activated K+ current (IK,Ca). IA activates and decays rapidly; the steady-state
      activation and inactivation curves of the current reveal a window current close
      to the apparent resting voltage of the hair cells, suggesting that the current is
      partially activated at rest. By modulating firing frequency and perhaps damping
      membrane oscillations, IA may regulate synaptic release at baseline. In contrast,
      IK,V and IK,Ca have slow onset and exhibit little or no inactivation. These two
      K+ currents may determine the duration of the repolarization phase of hair-cell
      action potentials and hence synaptic release via Ca2+ influx through voltage
      gated Ca2+ channels. In addition, IK,Ca may be responsible for the
      afterhyperpolarization of hair cell membrane voltage following prolonged
      stimulation.

PMID- 8994606
TI  - Hindered transport of macromolecules in isolated glomeruli. II. Convection and
      pressure effects in basement membrane.
AB  - The filtration rates for water and a polydisperse mixture of Ficoll across films
      of isolated glomerular basement membrane (GBM) were measured to characterize
      convective transport across this part of the glomerular capillary wall. Glomeruli
      were isolated from rat kidneys and the cells were removed by detergent lysis,
      leaving a preparation containing almost pure GBM that could be consolidated into
      a layer at the base of a small ultrafiltration cell. A Ficoll mixture with Stokes
      Einstein radii ranging from about 2.0 to 7.0 nm was labeled with fluorescein,
      providing a set of rigid, spherical test macromolecules with little molecular
      charge. Filtration experiments were performed at two physiologically relevant
      hydraulic pressure differences (delta P), 35 and 60 mmHg. The sieving coefficient
      (filtrate-to-retentate concentration ratio) for a given size of Ficoll tended to
      be larger at 35 than at 60 mmHg, the changes being greater for the smaller
      molecules. The Darcy permeability also varied inversely with pressure, averaging
      1.48 +/- 0.10 nm2 at 35 mmHg and 0.82 +/- 0.07 nm2 at 60 mmHg. Both effects could
      be explained most simply by postulating that the intrinsic permeability
      properties of the GBM change in response to compression. The sieving data were
      consistent with linear declines in the hindrance factors for convection and
      diffusion with increasing pressure, and correlations were derived to relate those
      hindrance factors to molecular size and delta P. Comparisons with previous Ficoll
      sieving data for rats in vivo suggest that the GBM is less size-restrictive than
      the cell layers, but that its contribution to the overall size selectivity of the
      barrier is not negligible. Theoretical predictions of the Darcy permeability
      based on a model in which the GBM is a random fibrous network consisting of two
      populations of fibers were in excellent agreement with the present data and with
      ultrastructural observations in the literature.

PMID- 8994605
TI  - Hindered transport of macromolecules in isolated glomeruli. I. Diffusion across
      intact and cell-free capillaries.
AB  - The filtrate formed by renal glomerular capillaries must pass through a layer of
      endothelial cells, the glomerular basement membrane (GBM), and a layer of
      epithelial cells, arranged in series. To elucidate the relative resistances of
      the GBM and cell layers to movement of uncharged macromolecules, we measured the
      diffusional permeabilities of intact and cell-free capillaries to narrow
      fractions of Ficoll with Stokes-Einstein radii ranging from 3.0 to 6.2 nm.
      Glomeruli were isolated from rat kidneys, and diffusion of fluorescein-labeled
      Ficoll across the walls of single capillary loops was monitored with a confocal
      microscopy technique. In half of the experiments the glomeruli were treated first
      to remove the cells, leaving skeletons that retained the general shape of the
      glomerulus and consisted almost entirely of GBM. The diffusional permeability of
      cell-free capillaries to Ficoll was approximately 10 to 20 times that of intact
      capillaries, depending on molecular size. Taking into account the blockage of
      much of the GBM surface by cells, the contribution of the GBM to the diffusional
      resistance of the intact barrier was calculated to be 13% to 26% of the total,
      increasing with molecular size. Thus, the GBM contribution, although smaller than
      that of the cells, was not negligible. The structure that is most likely to be
      responsible for the cellular part of the diffusional resistance is the slit
      diaphragm, which spans the filtration slit between epithelial foot processes. A
      novel hydrodynamic model was developed to relate the diffusional resistance of
      the slit diaphragm to its structure, which was idealized as a single layer of
      cylindrical fibers in a ladder-like arrangement.

PMID- 8994607
TI  - Permeability of acetic acid across gel and liquid-crystalline lipid bilayers
      conforms to free-surface-area theory.
AB  - Solubility-diffusion theory, which treats the lipid bilayer membrane as a bulk
      lipid solvent into which permeants must partition and diffuse across, fails to
      account for the effects of lipid bilayer chain order on the permeability
      coefficient of any given permeant. This study addresses the scaling factor that
      must be applied to predictions from solubility-diffusion theory to correct for
      chain ordering. The effects of bilayer chemical composition, temperature, and
      phase structure on the permeability coefficient (Pm) of acetic acid were
      investigated in large unilamellar vesicles by a combined method of NMR line
      broadening and dynamic light scattering. Permeability values were obtained in
      distearoylphosphatidylcholine, dipalmitoylphosphatidylcholine,
      dimyristoylphosphatidylcholine, and dilauroylphosphatidylcholine bilayers, and
      their mixtures with cholesterol, at various temperatures both above and below the
      gel-->liquid-crystalline phase transition temperatures (Tm). A new scaling
      factor, the permeability decrement f, is introduced to account for the decrease
      in permeability coefficient from that predicted by solubility-diffusion theory
      owing to chain ordering in lipid bilayers. Values of f were obtained by division
      of the observed Pm by the permeability coefficient predicted from a bulk
      solubility-diffusion model. In liquid-crystalline phases, a strong correlation (r
      = 0.94) between f and the normalized surface density sigma was obtained: in f =
      5.3 - 10.6 sigma. Activation energies (Ea) for the permeability of acetic acid
      decreased with decreasing phospholipid chain length and correlated with the
      sensitivity of chain ordering to temperature, [symbol: see text] sigma/[symbol:
      see text](1/T), as chain length was varied. Pm values decreased abruptly at
      temperatures below the main phase transition temperatures in pure
      dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine bilayers (30-60
      fold) and below the pretransition in dipalmitoylphosphatidylcholine bilayers (8
      fold), and the linear relationship between in f and sigma established for liquid
      crystalline bilayers was no longer followed. However, in both gel and liquid
      crystalline phases in f was found to exhibit an inverse correlation with free
      surface area (in f = -0.31 - 29.1/af, where af is the average free area (in
      square angstroms) per lipid molecule). Thus, the lipid bilayer permeability of
      acetic acid can be predicted from the relevant chain-packing properties in the
      bilayer (free surface area), regardless of whether chain ordering is varied by
      changes in temperature, lipid chain length, cholesterol concentration, or bilayer
      phase structure, provided that temperature effects on permeant dehydration and
      diffusion and the chain-length effects on bilayer barrier thickness are properly
      taken into account.

PMID- 8994608
TI  - Conformational analysis of neuropeptide Y-[18-36] analogs in hydrophobic
      environments.
AB  - The interactive and conformational behavior of a series of neuropeptide Y-[18-36]
      (NPY-[18-36]) analogs in hydrophobic environments have been investigated using
      reversed-phase high-performance liquid chromatography (RP-HPLC) and circular
      dichroism (CD) spectroscopy. The peptides studied comprised a series of 16
      analogs of NPY-[18-36], each containing a single D-amino acid substitution. The
      influence of these single L-->D substitutions on the alpha-helical conformation
      of the NPY-[18-36] analogs in different solvent environments was determined by CD
      spectroscopy. Retention parameters related to the hydrophobic contact area and
      the affinity of interaction were determined with an n-octadecyl (C18) adsorbent.
      Structural transitions for all peptides were manifested as significant changes in
      the hydrophobic binding domain and surface affinity between 4 degrees C and 37
      degrees C. The results indicated that the central region of NPY-[18-36] (residues
      23-33) is important for maintenance of the alpha-helical conformation. Moreover,
      L-->D amino acid residue substitutions within the N- and C-terminal regions, as
      well as Asn29 and Leu30, do not appear to affect the secondary structure of the
      peptide. These studies demonstrate that RP-HPLC provides a powerful adjunct for
      investigations into the induction of stabilized secondary structure in peptides
      upon their interaction with hydrophobic surfaces.

PMID- 8994609
TI  - Phospholipase A2 action on planar lipid bilayers generates a small, transitory
      current that is voltage independent.
AB  - Addition of either bee venom or Trimeresurus flavoviridis phospholipase A2 (PLA2)
      to the solution bathing the front side of a voltage-clamped, planar lipid bilayer
      consistently produced a transitory current lasting approximately 100 s. This
      current is consistent with anions moving through the membrane to the rear side.
      The peak current is independent of holding potential. PLA2 activity on
      phospholipid membranes not only produced a current but also led to membrane
      rupture within 300 s. The current depends on Ca2+ and lipid type. Addition of
      PLA2 in the absence of Ca2+ or to membranes made of nonsubstrate lipids (e.g.,
      glycerol monooleate or lysophosphatidylcholine) produced no current and did not
      break the bilayer. Peak current height, signal decay time, and time to membrane
      rupture all depended on PLA2 dose, whereas total charge produced was constant.
      This current does not flow through ion channels because there are no channels
      present and the current is not voltage dependent. The evidence is consistent with
      the hypothesis that the current is generated by the movement of ionized fatty
      acid produced by PLA2 action. These results demonstrate a simple method to
      measure enzyme activity in the presence of different substrates and varied
      environmental conditions.

PMID- 8994610
TI  - Rate constant of muscle force redevelopment reflects cooperative activation as
      well as cross-bridge kinetics.
AB  - The rate of muscle force redevelopment after release-restretch protocols has
      previously been interpreted using a simple two-state cross-bridge cycling model
      with rate constants for transitions between non-force-bearing and force-bearing
      states, f, and between force-bearing and non-force-bearing states, g. Changes in
      the rate constant of force redevelopment, as with varying levels of Ca2+
      activation, have traditionally been attributed to Ca(2+)-dependent f. The current
      work adds to this original model a state of unactivated, noncycling cross
      bridges. The resulting differential equation for activated, force-bearing cross
      bridges, Ncf, was Ncf = -[g+f(K/(K + 1))] Ncf+f(K/(K + 1))NT, where K is an
      equilibrium constant defining the distribution between cycling and noncycling
      cross-bridges and NT is the total number of cross-bridges. Cooperativity by which
      force-bearing cross-bridges participate in their own activation was introduced by
      making K depend on Ncf. Model results demonstrated that such cooperativity, which
      tends to enhance force generation at low levels of Ca2+ activation, has a counter
      intuitive effect of slowing force redevelopment. These dynamic effects of
      cooperativity are most pronounced at low Ca2+ activation. As Ca2+ activation
      increases, the cooperative effects become less important to the dynamics of force
      redevelopment and, at the highest levels of Ca2+ activation, the dynamics of
      force redevelopment reflect factors other than cooperative mechanisms. These
      results expand on earlier interpretations of Ca2+ dependence of force
      redevelopment; rather than Ca(2+)-dependent f, Ca(2+)-dependent force
      redevelopment arises from changing expressions of cooperativity between force
      bearing cross-bridges and activation.

PMID- 8994611
TI  - ATPase activity of myosin in hair bundles of the bullfrog's sacculus.
AB  - Mechanoelectrical transduction by a hair cell displays adaptation, which is
      thought to occur as myosin-based molecular motors within the mechanically
      sensitive hair bundle adjust the tension transmitted to transduction channels. To
      assess the enzymatic capabilities of the myosin isozymes in hair bundles, we
      examined the actin-dependent ATPase activity of bundles isolated from the
      bullfrog's sacculus. Separation of 32P-labeled inorganic phosphate from unreacted
      [gamma-32P]ATP by thin-layer chromatography enabled us to measure the liberation
      of as little as 0.1 fmol phosphate. To distinguish the Mg(2+)-ATPase activity of
      myosin isozymes from that of other hair-bundle enzymes, we inhibited the
      interaction of hair-bundle myosin with actin and determined the reduction in
      ATPase activity. N-ethylmaleimide (NEM) decreased neither physiologically
      measured adaptation nor the nucleotide-hydrolytic activity of a 120-kDa protein
      thought to be myosin 1 beta. The NEM-insensitive, actin-activated ATPase activity
      of myosin increased from 1.0 fmol x s-1 in 1 mM EGTA to 2.3 fmol x s-1 in 10
      microM Ca2+. This activity was largely inhibited by calmidazolium, but was
      unaffected by the addition of exogenous calmodulin. These results, which indicate
      that hair bundles contain enzymatically active, Ca(2+)-sensitive myosin
      molecules, are consistent with the role of Ca2+ in adaptation and with the
      hypothesis that myosin forms the hair cell's adaptation motor.

PMID- 8994612
TI  - Force enhancement without changes in cross-bridge turnover kinetics: the effect
      of EMD 57033.
AB  - The thiadiazinon derivative EMD 57033 has been found previously in cardiac muscle
      to increase isometric force generation without a proportional increase in fiber
      ATPase, thus causing a reduction in tension cost. To analyze the mechanism by
      which EMD 57033 affects the contractile system, we studied its effects on
      isometric force, isometric fiber ATPase, the rate constant of force redevelopment
      (k(redev)), active fiber stiffness, and its effect on Fo, which is the force
      contribution of a cross-bridge in the force-generating states. We used chemically
      skinned fibers of the rabbit psoas muscle. It was found that with 50 microM EMD
      57033, isometric force increases by more than 50%, whereas Kredev, active
      stiffness, and isometric fiber ATPase increase by at most 10%. The results show
      that EMD 57033 causes no changes in cross-bridge turnover kinetics and no changes
      in active fiber stiffness that would result in a large enough increase in
      occupancy of the force-generating states to account for the increase in active
      force. However, plots of force versus length change recorded during stretches and
      releases (T plots) indicate that in the presence of EMD 57033 the y(o) value (x
      axis intercept) for the cross-bridges becomes more negative while its absolute
      value increases. This might suggest a larger cross-bridge strain as the basis for
      increased active force. Analysis of T plots with and without EMD 57033 shows that
      the increase in cross-bridge strain is not due to a redistribution of cross
      bridges among different force-generating states favoring states of larger strain.
      Instead, it reflects an increased cross-bridge strain in the main force
      generating state. The direct effect of EMD 57033 on the force contribution of
      cross-bridges in the force-generating states represents an alternative mechanism
      for a positive inotropic intervention.

PMID- 8994613
TI  - Overall and internal dynamics of DNA as monitored by five-atom-tethered spin
      labels.
AB  - Electron paramagnetic resonance (EPR) spectra of the two-atom-tethered six
      membered ring thymidylate spin label (DUMTA) incorporated into duplexes of
      different sizes were found to display a helix length dependence and a local-order
      parameter S = 0.32 +/- 0.01 for B-DNA based on the dynamic cylinder model (Keyes,
      R. S., and A. M. Bobst. 1995. Detection of internal and overall dynamics of a two
      atom-tethered spin-labeled DNA. Biochemistry. 34:9265-9276). This sensitivity to
      size, which reflects global tumbling, is now reported for the more flexible five
      atom-tethered five-membered ring thymidylate spin label (DUAP) that can be
      readily incorporated enzymatically and sequence specifically into nucleic acids
      of different sizes. The DUAPs containing B-DNA systems were simulated with the
      same dynamic cylinder model, giving S = 0.20 +/- 0.01 for the more flexibly
      tethered spin label. This shows that S is dependent on tether length but not on
      global motion. An analysis with the same motional model of the B-Z transition in
      a (dG-dC)n polymer containing the five-atom-tethered six-membered ring cytidylate
      spin label (DCAT) (Strobel, O. K., R. S. Keyes, and A. M. Bobst. 1990b. Base
      dynamics of local Z-DNA conformations as detected by electron paramagnetic
      resonance with spin-labeled deoxycytidine analogues. Biochemistry. 29:8522-8528)
      revealed an increase in S from 0.15 +/- 0.01 to 0.26 +/- 0.01 in response to the
      B- to Z-DNA transition. This indicates that S is not only sensitive to tether
      length, but also to conformational changes in DNA. Both the DUAP- and the DCAT
      labeled systems were also simulated with a base disk model. From the DUAP
      spectral series, the perpendicular component of the correlation time tau
      perpendicular describing the spin-labeled base diffusion was found to be
      sensitive to global tumbling, confirming earlier results obtained with DUMTA. The
      DCAT polymer results demonstrated that tau perpendicular monitors a
      conformational change from B- to Z-DNA, indicating that tau perpendicular is also
      sensitive to local base dynamics. These results confirm that the dynamics of five
      atom-tethered nitroxides are coupled to the nucleic acid dynamics and, as with
      two-atom-tethered spin labels, can be characterized by S and tau perpendicular.
      The analyses of both spin-labeled systems provide good evidence for spin-labeled
      base motions within double-stranded DNA occurring on the nanosecond time scale,
      and establish that both labels can be used to monitor changes in global tumbling
      and local order parameter due to variations in DNA conformation and protein-DNA
      interactions.

PMID- 8994615
TI  - Near-IR absorbance changes and electrogenic reactions in the microsecond-to
      second time domain in Photosystem I.
AB  - The back-reaction kinetics in Photosystem I (PS I) were studied on the
      microsecond-to-s time scale in cyanobacterial preparations, which differed in the
      number of iron-sulfur clusters to assess the contributions of particular
      components to the reduction of P700+. In membrane fragments and in trimeric P700
      FA/FB complexes, the major contribution to the absorbance change at 820 nm (delta
      A820) was the back-reaction of FA- and/or FB- with lifetimes of approximately 10
      and 80 ms (approximately 10% and 40% relative amplitude). The decay of
      photoinduced electric potential (delta psi) across a membrane with directionally
      incorporated P700-FA/FB complexes had similar kinetics. HgCl2-treated PS I
      complexes, which contain FA but no FB, retain both of these kinetic components,
      indicating that neither can be assigned uniquely to a specific acceptor. These
      results suggest that FA- reduces P700+ directly and argue for a rapid electron
      equilibration between FA and FB, which would eliminate their kinetic distinction
      in a back-reaction. In PsaC-depleted P700-Fx cores, as well as in P700-FA/FB
      complexes with chemically reduced FA and FB, the major contribution to the delta
      A820 and the delta psi decay is a biphasic back-reaction of F-X (approximately
      400 microseconds and 1.5 ms) with some contribution from A-1 (approximately 10
      microseconds and 100 microseconds), the latter of which is variable depending on
      experimental conditions. The delta A820 decay in a P700-A1 core devoid of all
      iron-sulfur clusters comprises two phases with lifetimes of 10 microseconds and
      130 microseconds (2.7:1 ratio). The biexponential back-reaction kinetics found
      for each of the electron acceptors may be related to existence of different
      conformational states of the PS I complex. In all preparations studied,
      excitation at 532 nm with flash energies exceeding 10 mJ gives rise to formation
      of antenna 3Chl, which also contributes to delta A820 decay on the tens-of
      microsecond time scale. A distinction between delta A820 components related to
      back-reactions and to 3Chl decay can be made by analysis of flash saturation
      dependencies and by measurements of kinetics with preoxidized P700.

PMID- 8994614
TI  - Proton equilibria in the minor groove of DNA.
AB  - Poisson-Boltzmann calculations by Pack and co-workers suggest the presence of
      regions of increased hydrogen ion density in the grooves of DNA. As an
      experimental test of this prediction, we have attached proton-sensitive probes,
      with variable linker lengths, to random-sequence DNA at G sites in the minor
      groove. The amino groups of beta-alanine, gamma-aminobutyric acid (GABA), and
      epsilon-aminocaproic acid have been coupled at pH 5, via a formaldehyde link, to
      the exocyclic amino group of guanine, utilizing a reaction that has been
      extensively investigated by Hanlon and co-workers. The resulting adducts at pH 5
      retained duplex B form but exhibited typical circular dichroism (CD) changes
      previously shown to be correlated with the presence of a net positive charge in
      the minor groove. Increases in the solvent pH reversed the CD spectral changes in
      a manner suggesting deprotonation of the carboxylic acid group of the adduct.
      These data were used to calculate an apparent pK(a) for the COOH. The pK(a) was
      increased by 2.4 units for beta-alanine, by 1.7 units for GABA, and by 1.5 units
      for epsilon-amino caproic acid, relative to their values in the free amino acid.
      This agrees well with Poisson-Boltzmann calculations and the energy minimization
      of the structures of the adducts that place the carboxyl groups in acidic domains
      whose hydrogen ion density is approximately 2 orders of magnitude greater than
      that of bulk solvent.

PMID- 8994616
TI  - Redox effects on the excited-state lifetime in chlorosomes and
      bacteriochlorophyll c oligomers.
AB  - Oligomers of [E,E] BChl CF (8, 12-diethyl bacteriochlorophyll c esterified with
      farnesol (F)) and [Pr,E] BChl CF (analogously, M methyl, Pr propyl) in hexane and
      aqueous detergent or lipid micelles were studied by means of steady-state
      absorption, time-resolved fluorescence, and electron spin resonance spectroscopy.
      The maximum absorption wavelength, excited-state dynamics, and electron spin
      resonance (EPR) linewidths are similar to those of native and reconstituted
      chlorosomes of Chlorobium tepidum. The maximum absorption wavelength of oligomers
      of [E,E] BChl CF was consistently blue-shifted as compared to that of [Pr,E] BChl
      CF oligomers, which is ascribed to the formation of smaller oligomers with [E,E]
      BChl CF than [Pr,E] BChl CF. Time-resolved fluorescence measurements show an
      excited-state lifetime of 10 ps or less in nonreduced samples of native and
      reconstituted chlorosomes of Chlorobium tepidum. Under reduced conditions the
      excited-state lifetime increased to tens of picoseconds, and energy transfer to
      BChl a or long-wavelength absorbing BChl c was observed. Oligomers of [E,E] BChl
      CF and [Pr,E] BChl CF in aqueous detergent or lipid micelles show a similar short
      excited-state lifetime under nonreduced conditions and an increase up to several
      tens of picoseconds upon reduction. These results indicate rapid quenching of
      excitation energy in nonreduced samples of chlorosomes and aqueous BChl c
      oligomers. EPR spectroscopy shows that traces of oxidized BChl c radicals are
      present in nonreduced and absent in reduced samples of chlorosomes and BChl c
      oligomers. This suggests that the observed short excited-state lifetimes in
      nonreduced samples of chlorosomes and BChl c oligomers may be ascribed to excited
      state quenching by BChl c radicals. The narrow EPR linewidth suggests that the
      BChl c are arranged in clusters of 16 and 6 molecules in chlorosomes of
      Chlorobium tepidum and Chloroflexus aurantiacus, respectively.

PMID- 8994617
TI  - The use of a long-lifetime component of tryptophan to detect slow orientational
      fluctuations of proteins.
AB  - The membrane protein porin and a synthetic polypeptide of 21 hydrophobic residues
      were inserted into detergent micelles or lipid membranes, and the fluorescence of
      their single tryptophan residue was measured in the time-resolved and polarized
      mode. In all cases, the tryptophan fluorescence exhibits a long-lifetime
      component of about 20 ns. This long-lifetime component was exploited to detect
      slow orientational motions in the range of tens of nanoseconds via the anisotropy
      decay. For this purpose, the analysis of the anisotropy has to be extended to
      account for different orientations of the dipoles of the short- and long-lifetime
      components. This is demonstrated for porin and the polypeptide solubilized in
      micelles, in which the longest relaxation time reflects the rotational diffusion
      of the micelle. When the polypeptide is inserted into lipid membranes, it forms a
      membrane-spanning alpha-helix, and the slowest relaxation process is interpreted
      as reflecting orientational fluctuations of the helix.

PMID- 8994618
TI  - Small-angle neutron scattering by a strongly denatured protein: analysis using
      random polymer theory.
AB  - Small-angle neutron scattering profiles are presented from phosphoglycerate
      kinase, in the native form and strongly denatured in 4 M guanidinium chloride
      (GdnHCl) solution. The data are interpreted using a model in which the excess
      scattering density associated with the protein is represented as a finite freely
      jointed chain of spheres. The similarity of the model-derived scattering function
      to experiment increases asymptotically with the number of spheres. The
      improvement of the fit obtained with more than approximately 200 spheres (i.e.,
      two residues per sphere) is insignificant. The effects of finite size of the
      scattering units and of scattering length variation along the polypeptide chain
      are examined. Improved agreement with experiment is obtained when these effects
      are taken into account. A method for rapid calculation of the scattering profile
      of a full, all-atom configuration is examined. It is found that a representation
      of the chain containing two scattering units per residue, placed at the backbone
      and side-chain scattering length centroids, reproduces the full, all-atom profile
      to within 2%.

PMID- 8994619
TI  - Homogeneous nucleation in sickle hemoglobin: stochastic measurements with a
      parallel method.
AB  - The homogeneous nucleation rate for sickle hemoglobin polymerization has been
      measured for concentrations from 3.9 to 4.9 mM and temperatures from 13 degrees C
      to 35 degrees C by observing the stochastic fluctuations of the time to complete
      10% of the reaction after photolysis of the carboxy derivative. To allow
      efficient data collection, a mesh was used to divide the photolysis beam into an
      array of smaller beams, which allowed parallel observation of about 100 different
      regions. Nucleation rates measured here are consistent with more restricted
      previously published data and, when combined with directly measured monomer
      addition rates, are consistent with previous analysis of progress curves. By
      describing these rates with equilibrium nucleation theory, the concentration of
      nuclei and hence their stability can be ascertained. Consequently, the chemical
      potential by which a monomer is attached to the polymer is determined. This
      attachment energy ranges from -6.6 to -8.0 kcal/mol between 15 degrees C and 35
      degrees C. The enthalpic part of that chemical potential is found to be equal to
      the enthalpy determined by solubility measurements, as expected from
      thermodynamic considerations. The entropic portion of the contact chemical
      potential contributes from -21.4 to -8.7 kcal/mol. The vibrational chemical
      potential of monomers in the polymer ranges from -25.7 to -27.4 kcal/mol over the
      same temperatures.

PMID- 8994620
TI  - Solvent hydrogen-bond network in protein self-assembly: solvation of collagen
      triple helices in nonaqueous solvents.
AB  - Forces between type I collagen triple helices are studied in solvents of varying
      hydrogen-bonding ability. The swelling of collagen fibers in reconstituted films
      is controlled by the concentration of soluble polymers that are excluded from the
      fibers and that compete osmotically with collagen for available solvent. The
      interaxial spacing between the triple helices as a function of the polymer
      concentration is measured by x-ray diffraction. Exponential-like changes in the
      spacing with increasing osmotic stress, qualitatively similar to the forces
      previously found in aqueous solution, are also seen in formamide and ethylene
      glycol. These are solvents that, like water, are capable of forming three
      dimensional hydrogen-bond networks. In solvents that either cannot form a network
      or have a greatly impaired ability to form a hydrogen-bonded network, strikingly
      different behavior is observed. A hard-wall repulsion is seen with collagen
      solvated by ethanol, 2-propanol, and N,N-dimethylformamide. The spacing between
      helices hardly changes with increasing polymer concentration until the stress
      exceeds some threshold where removal of the solvent becomes energetically
      favorable. No solvation of collagen is observed in dimethoxyethane. In solvents
      with an intermediate ability to form hydrogen-bonded networks, methanol, 2
      methoxyethanol, or N-methylformamide, the change in spacing with polymer
      concentration is intermediate between exponential-like and hard-wall. These
      results provide direct evidence that the exponential repulsion observed between
      collagen helices at 0-8-A surface separations in water is due to the energetic
      cost associated with perturbing the hydrogen-bonded network of solvent molecules
      between the collagen surfaces.

PMID- 8994621
TI  - Bound ligand motion in crystalline carboxypeptidase A.
AB  - Deuterium NMR spectra for the phenyl ring deuterons have been obtained for D
      phenylalanine, L-phenylalanine, phenylacetic acid, and phenyl propionic acid in
      randomly oriented crystals of carboxypeptidase A as a function of water content.
      The spectra are analyzed using a two-site jump model for phenyl ring pi-flips
      when the ligand is bound to the protein, and the model includes the possibility
      that the ligand may exchange with isotropic or unbound environments within the
      crystal. Although the binding pocket may impose local dynamical constraints, a
      complete pi-flip motion is consistent with the spectra of all ligands at all
      water contents. The rate constants for the pi-flip at 298 K are found to be 7.5 x
      10(5) S-1, 1.9 x 10(6) S-1, 4.0 x 10(6) S-1, and 4.0 x 10(6) S-1 for L
      phenylalanine, D-phenylalanine, phenyl propionic acid, and phenylacetic acid,
      respectively, at water activity of 0.98. The pi-flip rate for the ligand bound to
      the enzyme increases with water content. Assuming that the activation barrier may
      be written, delta G+2 = delta G+2o + baw, where aw is the water activity, and the
      value of b is -1.9 kcal/mol for phenylacetic acid and phenyl propionic acid, -1.3
      kcal/mol for L-phenylalanine, and -2.1 kcal/mol for D-phenylalanine. Phenylacetic
      acid crystals were studied as an example of a phenyl ring motion that is highly
      constrained by a known and symmetrical packing environment. The deuterium spectra
      are complex and are not consistent with pi-flip motions, but they are consistent
      with a superposition of ring jump motions of 24 degrees, 34 degrees, and 72
      degrees, with probabilities in the ratio of 1:1:2. Because of the limited space
      for motion imposed by the tight packing in the crystal, these motions must be
      highly cooperative and probably locally coherent; however, the spectra by
      themselves do not prove this intuitively reasonable hypothesis.

PMID- 8994622
TI  - Triplet state magnetic resonance and fluorescence spectroscopy of metal
      substituted hemoglobins.
AB  - Fluorescence detected magnetic resonance (FDMR) spectra detected at 596 nm of
      zinc-substituted hemoglobins at 4.2 K show a split D-E transition, which is not
      observed for zinc protoporphyrins ligated by methylimidazole in glasses.
      Incorporation of the zinc heme into the globin pocket is also accompanied by a
      blue shift of the fluorescence of 20 nm at 4.2 K. FDMR spectra recorded at 576 nm
      do not show the D-E splitting. The D-E splitting and the huge blue shift are not
      observed for the magnesium-substituted hemoglobins. Fluorescence measurements at
      4.2 K and 77 K, and EPR measurements at 110 K, were carried out to obtain
      information about the ligation states of the zinc and magnesium protoporphyrins
      in glasses and in hemoglobin. The results are explained by considering ligation
      effects and distortion of the porphyrin plane.

PMID- 8994623
TI  - Binding to phosphatidyl serine membranes causes a conformational change in the
      concave face of annexin I.
AB  - Recent studies have revealed that binding of annexin I to phospholipids induces
      the formation of a second phospholipid binding site. It is shown that the N
      terminus on the concave side of membrane-bound annexin I is cleaved much faster
      by trypsin or cathepsin than the N terminus of the free protein. The reactivity
      of the unique disulfide bond located near the concave face was similarly
      increased by membrane binding. These results demonstrate that Ca(2+)-dependent
      membrane binding induces a conformational change on the concave side of the
      annexin I molecule and support the notion that this face of the molecule may
      contribute to the formation of the secondary membrane-binding site.

PMID- 8994624
TI  - Mesoscopic gels at low agarose concentration: perturbation effects of ethanol.
AB  - Aqueous agarose solutions at low concentrations (0.5 g/liter) were temperature
      quenched below the spinodal line to form mutually disconnected mesoscopic gels.
      In the presence of 6% ethanol, these solutions, obtained by quenching at the same
      temperature depth as in pure water, appear much more fluid, as determined by
      probe diffusion experiments. We show by static and dynamic light scattering that
      this can be explained by the solvent-mediated effects of ethanol, leading to a
      globular shape of mesoscopic agarose gels, rather than to an extended rodlike
      structure observed in pure water. Our findings show the significant effects of
      solvent perturbations on particle condensation and, therefore, may be useful in
      understanding the role of the solvent in the folding of biomolecules.

PMID- 8994625
TI  - Advances in sedimentation velocity analysis.
AB  - On February 20, 1996, a workshop titled "Advances in Sedimentation Velocity
      Analysis" was held at the Biophysical Society meeting in Baltimore, Maryland, in
      honor of Professor David Yphantis's 65th birthday. Although he is known more for
      his work with sedimentation equilibrium, David's work on instrumentation and data
      analysis is the foundation for many of the recent advances in both equilibrium
      and velocity sedimentation. Over the years he has trained numerous graduate
      students, most of whom have gone on to emphasize the use of analytical
      ultracentrifugation to answer biochemical questions involving macromolecular
      assembly. His laboratory was one of very few that continued to use and develop
      analytical ultracentrifugation during its nadir in the 1970s and early 1980s. The
      rebirth and resurgence of analytical ultracentrifugation owe a great deal to his
      persistence and enthusiasm. These efforts have borne fruit. In the last five
      years, through his work at the National Analytical Ultracentrifugation Facility,
      he has helped train nearly 100 individuals in the delicate art of nonlinear least
      squares analysis of equilibrium sedimentation data. Furthermore, the number of
      researchers using the ultracentrifuge and the number of papers published has
      skyrocketed in the last few years. This workshop, then, was a way to thank David
      for his years of devotion to analytical ultracentrifugation.

PMID- 8994626
TI  - Identification and interpretation of complexity in sedimentation velocity
      boundaries.
AB  - Synthetic sedimentation velocity boundaries were generated using finite-element
      solutions to the original and modified forms of the Lamm equation. Situations
      modeled included ideal single- and multicomponent samples, concentration
      dependent samples, noninteracting multicomponent samples, and reversibly self
      associating samples. Synthetic boundaries subsequently were analyzed using the
      method of van Holde and Weischet, and results were compared against known input
      parameters. Results indicate that this analytical method provides rigorous
      diagnostics for virtually every type of sample complexity encountered
      experimentally. Accordingly, both the power and utility of sedimentation velocity
      experiments have been significantly expanded.

PMID- 8994627
TI  - Construction of hydrodynamic bead models from high-resolution X-ray
      crystallographic or nuclear magnetic resonance data.
AB  - Computer software such as HYDRO, based upon a comprehensive body of theoretical
      work, permits the hydrodynamic modeling of macromolecules in solution, which are
      represented to the computer interface as an assembly of spheres. The uniqueness
      of any satisfactory resultant model is optimized by incorporating into the
      modeling procedure the maximal possible number of criteria to which the bead
      model must conform. An algorithm (AtoB, for atoms to beads) that permits the
      direct construction of bead models from high resolution x-ray crystallographic or
      nuclear magnetic resonance data has now been formulated and tested. Models so
      generated then act as informed starting estimates for the subsequent iterative
      modeling procedure, thereby hastening the convergence to reasonable
      representations of solution conformation. Successful application of this
      algorithm to several proteins shows that predictions of hydrodynamic parameters,
      including those concerning solvation, can be confirmed.

PMID- 8994629
TI  - Molecular mass determination by sedimentation velocity experiments and direct
      fitting of the concentration profiles.
AB  - A new method for the direct molecular mass determination from sedimentation
      velocity experiments is presented. It is based on a nonlinear least squares
      fitting procedure of the concentration profiles and simultaneous estimation of
      the sedimentation and diffusion coefficients using approximate solutions of the
      Lamm equation. A computer program, LAMM, was written by using five different
      model functions derived by Fujita (1962, 1975) to describe the sedimentation of
      macromolecules during centrifugation. To compare the usefulness of these
      equations for the analysis of hydrodynamic results, the approach was tested on
      data sets of Claverie simulations as well as experimental curves of some
      proteins. A modification for one of the model functions is suggested, leading to
      more reliable sedimentation and diffusion coefficients estimated by the fitting
      procedure. The method seems useful for the rapid molecular mass determination of
      proteins larger than 10 kDa. One of the equations of the Archibald type is also
      suitable for compounds of low molecular mass, probably less than 10 kDa, because
      this model function requires neither the plateau region nor a meniscus free of
      solute.

PMID- 8994630
TI  - An improved function for fitting sedimentation velocity data for low-molecular
      weight solutes.
AB  - Many traditional approaches to the analysis of sedimentation velocity data work
      poorly with data for low-molecular-weight solutes, which have sedimentation
      boundaries that are severely broadened by diffusion. An approach that has
      previously had some success is to directly fit these broad boundaries to
      approximate solutions of the Lamm equation that directly account for the high
      diffusion. However, none of the available approximate solutions work well at
      times both early and late in the run, or give boundary shapes that are highly
      accurate, especially for species of molecular weight < 10,000. An improved
      fitting function has been developed to overcome some of these limitations. The
      new function adds two correction terms to the Fujita-MacCosham solution. The
      optimum coefficients for these new correction terms were determined by a least
      squares approach. The accuracy and limitations of fitting with this new function
      were tested against synthetic data sets obtained by finite-element methods, for
      analysis of samples containing either single species or several noninteracting
      species. We also compare the strengths and weaknesses of this method of analysis,
      and its ability to work with noisy data, relative to recently developed time
      derivative methodologies.

PMID- 8994631
TI  - Atomic force microscope imaging contrast based on molecular recognition.
AB  - The contrast in atomic force microscope images arises from forces between the tip
      and the sample. It was shown recently that specific molecular interaction forces
      may be measured with the atomic force microscope; consequently, we use such
      forces to map the distribution of binding partners on samples. Here we
      demonstrate this concept by imaging a streptavidin pattern with a biotinylated
      tip in a novel imaging mode called affinity imaging. In this mode topography,
      adhesion, and sample elasticity are extracted online from local force scans. We
      show that this technique allows the separation of these values and that the
      measured binding pattern is based on specific molecular interactions.

PMID- 8994628
TI  - Divalent cation and ionic strength effects on Vinca alkaloid-induced tubulin self
      association.
AB  - We present here a systematic study of ionic strength and divalent cation effects
      on Vinca alkaloid-induced tubulin spiral formation. We used sedimentation
      velocity experiments and quantitative fitting of weight-average sedimentation
      coefficients versus free drug concentrations to obtain thermodynamic parameters
      under various solution conditions. The addition of 50-150 mM NaCl to our standard
      buffer (10 mM piperazine-N,N'-bis(2-ethanesulfonic acid), 1 mM Mg, 50 microM GDP
      or GTP, pH 6.9) enhances overall vinblastine- or vincristine-induced tubulin self
      association. As demonstrated in previous studies, GDP enhances overall self
      association more than GTP, although in the presence of salt, GDP enhancement is
      reduced. For example, in 150 mM NaCl, GDP enhancement is 0.24 kcal/mol for
      vinblastine and 0.36 kcal/mol for vincristine versus an average enhancement of
      0.87 (+/- 0.34) kcal/mol for the same drugs in the absence of salt. Wyman linkage
      analysis of experiments with vinblastine or vincristine over a range of NaCl
      concentrations showed a twofold increase in the change in NaCl bound to drug
      induced spirals in the presence of GTP compared to GDP. These data indicate that
      GDP enhancement of Vinca alkaloid-induced tubulin self-association is due in part
      to electrostatic inhibition in the GTP state. In the absence of NaCl, we found
      that vinblastine and 1 mM Mn2+ or Ca2+ causes immediate condensation of tubulin.
      The predominant aggregates observed by electron microscopy are large sheets. This
      effect was not found with 1 mM Mg2+. At 100 microM cation concentrations (Mn2+,
      Mg2+, or Ca2+), GDP enhances vinblastine-induced spiral formation by 0.55 (+/-
      0.26) kcal/mol. This effect is found only in K2, the association of liganded
      heterodimers at the ends of growing spirals. There is no GDP enhancement of K1,
      the binding of drug to heterodimer, although K1 is dependent upon the divalent
      cation concentration. NaCl diminishes tubulin condensation, probably by
      inhibiting lateral association, and allows an investigation of higher divalent
      cation concentrations. In the presence of 150 mM NaCl plus 1 mM divalent cations
      (Mn2+, Mg2+, or Ca2+) GDP enhances vinblastine-induced spiral formation by 0.35
      (+/- 0.21) kcal/mol. Relaxation times determined by stopped-flow light scattering
      experiments in the presence of 150 mM NaCl and vincristine are severalfold longer
      than those in the presence of vinblastine, consistent with a mechanism involving
      the redistribution of longer polymers. Unlike previous results in the absence of
      NaCl, relaxation times in the presence of NaCl are only weekly protein
      concentration dependent, suggesting the absence of annealing or an additional
      rate-limiting step in the mechanism.

PMID- 8994632
TI  - Extraction of cilium beat parameters by the combined application of photoelectric
      measurements and computer simulation.
AB  - Photoelectric signals were created and used to investigate the features of the
      signals as a function of the ciliary beat parameters. Moreover, correlation
      between the simulated and the measured signals permitted measurement of the
      cilium beat parameters. The simulations of the signals were based on generation
      of a series of time-frozen top-view frames of an active ciliary area and
      determination of the amount of light passing through an observation area in each
      of these frames. All the factors that might contribute to the shape of the
      signals, namely, partial ciliary transmittance of light, three-dimensional
      ciliary beat (composed of recovery, effective, and pause parts), phase
      distribution on the ciliary surface, and the large number of cilia that
      contribute to the photoelectric signal, were taken into account in generation of
      the signals. Changes in the ciliary parameters influenced the shape of the
      photoelectric signals, and the different phases of the beat could not be directly
      and unequivocally identified in the signals. The degree of temporal asymmetry of
      the beat and the portion of the cycle occupied by the pause significantly
      influenced the shapes of both the lower and the upper parts of the signal and the
      slopes of the signal. Increases in the angle of the arc swept by the cilium
      during the effective stroke smoothed the signals and increased the duration of
      the upper part of the signal. The angle of the arc projected by the cilium onto
      the cell surface during the recovery stroke had minor effects on the signal's
      shape. Characteristics of the metachronal wave also influenced the signal's shape
      markedly. Decreases in ciliary spacing smoothed the signals, whereas ciliary
      length had a minor influence on the simulated photoelectric signals. Comparison
      of the simulated and the measured signals showed that the beat parameters of the
      best-fitting simulated signals converged to values that agree well with the
      accepted range of beat parameters in mucociliary systems.

PMID- 8994633
TI  - The structure of a model pulmonary surfactant as revealed by scanning force
      microscopy.
AB  - The structures formed by a pulmonary surfactant model system of
      dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG),
      and recombinant surfactant-associated protein C (SP-C) were studied using
      scanning force microscopy (SFM) on Langmuir-Blodgett films. The films appeared to
      be phase separated, in agreement with earlier investigations by fluorescence
      light microscopy. There were smooth polygonal patches of mostly lipid, surrounded
      by a corrugated rim rich in SP-C. When the films were compressed beyond the
      equilibrium surface pressure, the protein-rich phase mediated the formation of
      layered protrusions. The height of these multilamellar structures embodied
      equidistant steps slightly higher than a DPPC double layer in the gel phase. At
      the air-water interface too, a high compressibility at low surface tension was
      indicative of the exclusion of matter. The exclusion process proved to be fully
      reversible. The present study demonstrates that some of the matter of the model
      pulmonary surfactant can move in and out of the active monolayer. The SFM images
      revealed a lipid-protein complex that was responsible for the reversible
      exclusion of double-layer structures. This mechanism may be important in the
      natural system too, to keep the surface tension of the alveolar air/water
      interface constantly low over the range of area encountered upon breathing.

PMID- 8994635
TI  - Energy filtered electron tomography of ice-embedded actin and vesicles.
AB  - Semiautomatic single-axis tilt electron tomography has been used to visualize the
      three-dimensional organization of actin filaments in "phantom cells," i.e. lipid
      vesicles. The instrumentation consisted of a 120-kV electron microscope equipped
      with a postcolumn energy filter, which was used in the zero-loss imaging mode.
      Apart from changing the tilt angle, all steps required for automated tomography,
      such as recentering the image area, refocusing, and centering the energy
      selecting slit, were performed by external computer control. This setup permitted
      imaging of ice-embedded samples up to a thickness of 800 nm with improved image
      contrast compared with that produced by tomography with a conventional electron
      microscope. In spite of the missing-wedge effect that is especially obvious in
      the study of membrane-filament interaction, single-axis tilt tomography was found
      to be an appropriate (in fact the only available) method for this kind of
      investigation. In contrast to random actin networks found in actin gels, actin
      filaments in and on vesicles with a bending radius of less than approximately 2
      microns tend to be arranged in single layers of parallel filaments and often
      induce an elongated shape of the vesicles. Actin filaments located on the outside
      usually associate with the vesicle membrane.

PMID- 8994634
TI  - Molecular motions of a glycopeptide from human serum transferrin studied by 13C
      nuclear magnetic resonance.
AB  - The molecular motions of a 21-amino-acid glycopeptide (Gp21) containing multiple
      glycoforms of an N-linked diantennary oligosaccharide were studied by two
      dimensional 1H-detected 13C relaxation measurements at natural abundance. Gp21
      was derived from human serum transferrin, its amino acid sequence is
      QQQHLFGSNVTDCSGNFCLFR, and its N-glycan structure is [Formula: see text] The
      measured longitudinal and transverse relaxation rate constants and the nuclear
      Overhauser enhancements for the methine carbons of Gp21 were analyzed by using
      the model-free approach to obtain information about the internal motions in the
      molecule. The calculated order parameters S2 of the alpha carbons in both NH2-
      and COOH-terminal segments of the peptide are smaller than those in the interior
      segment of the Gp21 peptide moiety, implying that the internal motions in the
      terminal segments are less restricted than in the interior segment. The average
      S2 value is 0.72-0.91 for the glycosyl residues in the pentasaccharide core of
      Gp21, 0.58-0.59 for the interior GlcNAc-5,5' residues in the two branches, and
      0.35-0.51 for the terminal GlcNAc-5, Gal-6,6', and NeuAcN,N' residues in the two
      branches, indicating that the internal motions in the glycan core are more
      restricted than in the two branches.

PMID- 8994637
TI  - Nonradioactive method for quantitation of PCR products without hybridization with
      a specific probe.

PMID- 8994636
TI  - 19F NMR measurements of the rotational mobility of proteins in vivo.
AB  - Three glycolytic enzymes, hexokinase, phosphoglycerate kinase, and pyruvate
      kinase, were fluorine labeled in the yeast Saccharomyces cerevisiae by
      biosynthetic incorporation of 5-fluorotryptophan. 19F NMR longitudinal relaxation
      time measurements on the labeled enzymes were used to assess their rotational
      mobility in the intact cell. Comparison with the results obtained from relaxation
      time measurements of the purified enzymes in vitro and from theoretical
      calculations showed that two of the labeled enzymes, phosphoglycerate kinase and
      hexokinase, were tumbling in a cytoplasm that had a viscosity approximately twice
      that of water. There were no detectable signals from pyruvate kinase in vivo,
      although it could be detected in diluted cell extracts, indicating that there was
      some degree of motional restriction of the enzyme in the intact cell.

PMID- 8994638
TI  - Screening for homologous recombination in ES cells using RT-PCR.

PMID- 8994639
TI  - Simultaneous introduction of multiple mutations using overlap extension PCR.

PMID- 8994640
TI  - Primer-directed mutagenesis of an intact plasmid by using Pwo DNA polymerase in
      long distance inverse PCR.

PMID- 8994641
TI  - Ligation of single adaptors allows efficient cloning of long PCR products.

PMID- 8994642
TI  - Optimized conditions for cloning PCR products into an XcmI T-vector.

PMID- 8994643
TI  - Universal primers for sequencing DNA restriction fragments.

PMID- 8994644
TI  - Improved method for isolation of DNA from slow-growing basidiomycetes such as
      Armillaria mellea.

PMID- 8994645
TI  - Enhancement of transformation in Pseudomonas aeruginosa PAO1 by Mg2+ and heat.

PMID- 8994646
TI  - Rapid method for cloning a Ca(2+)-dependent metalloprotease from a gram-positive
      bacterium in Escherichia coli.

PMID- 8994647
TI  - Simplified selection of transgenic Arabidopsis thaliana seed in liquid culture.

PMID- 8994649
TI  - Mammalian expression vector with two multiple cloning sites for expression of two
      foreign genes.

PMID- 8994648
TI  - Discrimination of run-on transcription from constitutive genes and antisense
      expression vectors in the same cells.

PMID- 8994650
TI  - Site-directed mutagenesis for large insertions by oligonucleotide primers in
      optimized molar ratios.

PMID- 8994651
TI  - Reduction of background in protein kinase assays by electroblotting.

PMID- 8994652
TI  - Removal of an inhibitor of marker enzyme activity in artery extracts by chelating
      agents.

PMID- 8994653
TI  - Fabrication of an autoclavable one-way valve for venting fermentation gases.

PMID- 8994654
TI  - Rapid purification of microtubule motor domain proteins expressed in bacteria.

PMID- 8994655
TI  - Method for simultaneous RNA and DNA isolation from biopsy material, culture
      cells, plants and bacteria.

PMID- 8994656
TI  - Immunobead RT-PCR: a sensitive method for detection of circulating tumor cells.
AB  - Detection of circulating tumor cells and micrometastases in patients with cancer
      should prove useful in determining prognosis and in planning and monitoring
      systemic therapies. We have developed immunomagnetic isolation of carcinoma cells
      followed by reverse transcription polymerase chain reaction (immunobead RT-PCR)
      as a method for identifying very small numbers of breast cancer cells in blood.
      The expression of cytokeratin 19 (K19) was used as the marker by which the
      isolated tumor cells were identified. The immunobead RT-PCR technique allowed
      detection of one tumor cell per 10(6) leukocytes in whole blood. Immunobead RT
      PCR is a highly sensitive method of detecting cancer cells in a hematopoietic
      environment.

PMID- 8994657
TI  - Deoxyribonuclease treatment improves the homogeneity of single-stranded DNA
      preparations.
AB  - The isolation of single-stranded (ss) phagemid DNA using standard protocols often
      results in impure preparations, which contain undesirable quantities of
      chromosomal and/or double-stranded (ds) phagemid DNA. Here we report a simple and
      efficient method for elimination of virtually all dsDNA by incubation of phagemid
      viral particles with deoxyribonuclease I. In addition to analyzing the ratio of
      linear-to-circular topological forms of ssDNA after deoxyribonuclease I
      treatment, we verified that no decrease in transformation efficiency occurred and
      demonstrated that ssDNA molecules covered by capsid proteins remained intact
      following such treatment.

PMID- 8994658
TI  - Relationship between opacity of transformed E. coli colonies and over-expression
      of the recombinant transcript.
AB  - Following transformation with recombinant plasmid clones, E. coli BL21(DE3) often
      produced extremely opaque colonies on a standard semisolid agar plate, as
      compared with the translucent colonies produced by normal, untransformed bacteria
      A standard BL21(DE3) culture consisted of two kinds of cells one kind produced
      translucent colonies and the other produced opaque colonies upon transformation
      by recombinant plasmids. The translucent-generating phenotype often switched to
      the opaque-generating phenotype, which was irreversible. Opacity in the BL21(DE3)
      background was correlated to a higher preinduced level of T7 RNA polymerase,
      presumably through a stable and inheritable genetic change. In all E. coli
      strains tested, a robust transcription of the recombinant gene from the plasmid
      clone was found to be an essential prerequisite for every high opacity;
      translation of the RNA was not required. The degree of opacity was also
      determined by the nature of the insert in a given strain background. Colony,
      opacity generally, but not invariably, correlated with a smaller colony size on
      semisolid agar and a reduced growth rate in liquid culture.

PMID- 8994659
TI  - Methods and applications of three-color confocal imaging.
AB  - A simple method for constructing two- and three-color merged images from
      grayscale confocal fluorescence images using Adobe Photoshop is outlined. Various
      computer methods for manipulating and displaying the images are discussed in
      light of several recent biomedical applications of multi-label confocal
      microscopy.

PMID- 8994660
TI  - Continuous fluorescence monitoring of rapid cycle DNA amplification.
AB  - Rapid cycle DNA amplification was continuously monitored by three different
      fluorescence techniques. Fluorescence was monitored by (i) the double-strand
      specific dye SYBR Green I, (ii) a decrease in fluorescein quenching by rhodamine
      after exonuclease cleavage of a dual-labeled hydrolysis probe and (iii) resonance
      energy transfer of fluorescein to Cy5 by adjacent hybridization probes.
      Fluorescence data acquired once per cycle provides rapid absolute quantification
      of initial template copy number. The sensitivity of SYBR Green I detection is
      limited by nonspecific product formation. Use of a single exonuclease hydrolysis
      probe or two adjacent hybridization probes offers increasing levels of
      specificity. In contrast to fluorescence measurement once per cycle, continuous
      monitoring throughout each cycle monitors the temperature dependence of
      fluorescence. The cumulative, irreversible signal of hydrolysis probes can be
      distinguished easily from the temperature-dependent, reversible signal of
      hybridization probes. By using SYBR Green I, product denaturation, annealing and
      extension can be followed within each cycle. Substantial product-to-product
      annealing occurs during later amplification cycles, suggesting that product
      annealing is a major cause of the plateau effect. Continuous within-cycle
      monitoring allows rapid optimization of amplification conditions and should be
      particularly useful in developing new, standardized clinical assays.

PMID- 8994661
TI  - Specific detection of his-tagged proteins with recombinant anti-His tag scFv
      phosphatase or scFv-phage fusions.
AB  - Using a cell-bound immunogen, we have generated a monoclonal antibody, 3D5, that
      recognizes carboxy-terminal oligo-histidine tags (His tags) on a wide variety of
      proteins. From this monoclonal antibody, we have generated a single-chain
      fragment of the variable domains (scFv), a dimeric scFv-alkaline phosphatase
      fusion and an oligovalent scFv-display phage. The antibody in its various formats
      is an effective tool used in fluorescence-activated cell sorting analysis, the
      BIAcore method, Western blots and enzyme-linked immunosorbent assay (ELISA).
      Western blots and ELISAs can be developed directly by using crude extracts of
      E.coli cells that produce the scFv-alkaline phosphatase fusion, thus providing an
      inexhaustable and convenient supply of detection reagent. Alternatively,
      oligovalent scFv-displaying phage can be used directly from culture supernatants
      for this purpose. The dissociation constants, KD of the peptide KGGHHHHH (KD = 4
      x 10(-7) M) and of imidazole (KD = 4 x 10(-4) M) were determined. Molecular
      modeling of the Fv fragment suggests the occurrence of two salt bridges between
      the protonated histidine side chains of the peptide and the acidic groups in the
      antibody, explaining why the antibody or the substrate may be eluted under mildly
      basic conditions.

PMID- 8994662
TI  - Use of a dicistronic expression cassette encoding the green fluorescent protein
      for the screening and selection of cells expressing inducible gene products.
AB  - To facilitate the screening and selection of cells expressing inducible gene
      products, we have constructed a plasmid that, by the inclusion of a viral
      internal ribosome entry site, permits the synthesis of a dicistronic mRNA
      encoding both a gene of interest and the gene encoding the green fluorescent
      protein (GFP) from the jellyfish Aequorea victoria. This greatly simplifies the
      task of clone selection, since GFP fluorescence can be visualized non-obtrusively
      in live cells with a standard fluorescence microscope. We have applied this
      method to the tetracycline-regulated expression system in which the expression of
      a target gene, placed under the control of a promoter containing the tetracycline
      operator sequence (tetO), can be induced by a tetracycline-regulated trans
      activator protein (tTA). Binding of the tTA to the tetO is inhibited in the
      presence of tetracycline. Optimal results with this system require two sequential
      rounds of transfection and screening. Obtaining a cell line expressing high
      levels of functional tTA is greatly simplified by transiently transfecting a
      plasmid encoding GFP into a pool of cells that has first been transfected with a
      tTA-expressor construct and selecting GFP-positive cells using a fluorescence
      activated cell sorter. In the second step, the tTA cell line can then be stably
      transfected with a dicistronic expressor-GFP cassette. This method eliminates the
      task of characterizing cell lines by the standard method of examining levels of
      the exogenously expressed protein in cell extracts of individual clones.

PMID- 8994663
TI  - Tracking and quantitation of retroviral-mediated transfer using a completely
      humanized, red-shifted green fluorescent protein gene.
AB  - We have developed murine retroviral vectors (RVs) containing an optimized green
      fluorescent protein (GFP) gene to study retroviral gene transfer and expression
      in living cells. We used the codon "humanized", "red-shifted" GFP gene, hGFP
      S65T, a gain of function variant of the wild-type GFP from the jellyfish Aequorea
      victoria. We cloned the hGFP-S65T gene into the RV plasmid pLNCX (pLNChG65T). A
      stable amphotropic RV-producer cell line (VPC), designated LNChG65T VPC, was
      generated that exhibited bright fluorescence in greater than 95% of the cells.
      Human A375 melanoma cells and IGROV ovarian carcinoma cells transduced from LNCh
      G65T VPC demonstrated high levels of fluorescence. The expression of a single
      integrated hGFP-S65T gene in eukaryotic cells provides a powerful tool to study
      gene transfer, expression and functional studies in vitro and in vivo.

PMID- 8994664
TI  - Analysis of differential display RT-PCR products using fluorescent primers and
      GENESCAN software.
AB  - Differential display reverse transcription PCR (DDRT-PCR) is a procedure used to
      identify the induction or repression of gene expression. In most DDRT-PCR
      protocols, radioisotopes are incorporated during PCR and the cDNA products are
      detected by autoradiography. This report describes the fluorescent labeling of
      cDNAs and their detection on automated sequencers from PE Applied Biosystems. A
      fluorescent tag can be incorporated into the PCR product by using either a
      labeled primer or a labeled dUTP. The fluorescent signals are analyzed by
      GENESCAN software. Fluorescent DDRT-PCR increases throughput and obviates the
      handling of hazardous radioisotopes. A PCR cycling profile, expected to give
      improved reproducibility, is also described. Because amplified cDNAs can't be
      recovered from the automated sequencer gel, suggestions are given for the
      identification and recovery of differentially expressed cDNAs.

PMID- 8994665
TI  - The LightCycler: a microvolume multisample fluorimeter with rapid temperature
      control.
AB  - Experimental and commercial microvolume fluorimeters with rapid temperature
      control are described. Fluorescence optics adopted from flow cytometry were used
      to interrogate 1-10-microL samples in glass capillaries. Homogeneous temperature
      control and rapid change of sample temperatures (10 degrees C/s) were obtained by
      a circulating air vortex. A prototype 2-color, 32-sample version was constructed
      with a xenon arc for excitation, separate excitation and emission paths, and
      photomultiplier tubes for detection. The commercial LightCycler, a 3-color, 24
      sample instrument, uses a blue light-emitting diode for excitation, paraxial epi
      illumination through the capillary tip and photodiodes for detection.
      Applications include analyte quantification and nucleic acid melting curves with
      fluorescent dyes, enzyme assays with fluorescent substrates and techniques that
      use fluorescence resonance energy transfer. Microvolume capability allows
      analysis of very small or expensive samples. As an example of one application,
      rapid cycle DNA amplification was continuously monitored by three different
      fluorescence techniques, Which included using the double-stranded DNA dye SYBR
      Green I, a dual-labeled 5'-exonuclease hydrolysis probe, and adjacent fluorescein
      and Cy5z-labeled hybridization probes. Complete amplification and analysis
      requires only 10-15 min.

PMID- 8994696
TI  - Pre- and perinatal hazards and family background in children with specific
      language impairments: a study of twins.
AB  - A clinical group composed of 84 twin pairs where one or both twins met stringent
      psychometric criteria for specific speech-language impairment was compared with
      36 twin pairs with no history of speech-language difficulties. Twins with speech
      language impairment tended to have more siblings than control twins and were
      significantly more likely to have an affected parent. Groups were closely similar
      in terms of length of gestation and mother's antenatal condition, except that
      maternal toxemia was unusually frequent in the clinical group. Children from the
      two groups did not differ in terms of Apgar scores or on a composite measure of
      perinatal hazards. Within the clinical group, MZ pairs with substantial
      differences in neonatal status did not differ in language outcome. It is
      suggested that if an association with toxemia can be replicated, this might
      reflect a common genetic basis for immune disorders and developmental language
      delay. Perinatal hazard was unrelated to subtype of speech-language impairment.

PMID- 8994697
TI  - Lateralization of affective prosody in brain and the callosal integration of
      hemispheric language functions.
AB  - Although affective prosody appears to be a dominant function of the right
      hemisphere, its degre of lateralization has not yet been established since
      various publications have reported affective-prosodic deficits following left
      brain damage in association with aphasia. This paper explores the mechanisms
      underlying affective-prosodic deficits following left and right brain damage by
      testing the ability of subjects to repeat and comprehend affective prosody under
      progressively reduced verbal-articulatory conditions. The results demonstrate
      that reducing verbal-articulatory conditions robustly improves the performance of
      left but not right brain damaged patients, a finding that supports the
      supposition that affective prosody is strongly lateralized to the right
      hemisphere. However, the performance of left brain damaged patients was not
      correlated to the presence, severity, or type of aphasic deficit(s). Based on
      functional-anatomic correlations for spontaneous affective prosody and affective
      prosodic repetition, deep white matter lesions located below the supplementary
      motor area that disrupt interhemispheric connections coursing through the mid
      rostral corpus callosum may contribute to affective-prosodic deficits that are
      both additive and independent of any aphasic deficits. In light of these and
      other findings, various anatomical, functional, and maturational hierarchic
      relationships between the affective-prosodic and verbal-linguistic aspects of
      language are posited in order to help further explain discrepancies that exist in
      the literature regarding the neurology of affective prosody.

PMID- 8994698
TI  - A PET follow-up study of recovery after stroke in acute aphasics.
AB  - The neural correlates of recovery from aphasia are largely unknown. Several
      different sources of evidence, from clinical studies to neurophysiological
      investigations, have suggested a contribution of the contralateral, undamaged
      hemisphere in recovery from aphasia. Eight patients with unilateral left
      hemispheric stroke were submitted to a standard language examination and to a
      [18F]FDG PET study in the recent phase after stroke (within 2 weeks) and 6 months
      later. All patients had a substantial recovery of specific aspects of language
      functions at the follow-up. Analysis of regional glucose metabolism showed
      hypometabolism in structurally unaffected regions both in the left and in the
      right hemisphere (diaschisis), in the acute stage. Glucose metabolism increased
      significantly on both sides in all patients at the second PET study. Regional
      analysis showed significant positive correlations between changes in metabolic
      values in several cortical and subcortical regions in the right hemisphere and
      changes in language performance at follow-up. The present findings show that an
      extensive, bihemispheric depression of metabolism is found in the acute stage
      after stroke in aphasic patients. Language recovery in the first months after
      aphasia onset is associated with regression of functional depression (diaschisis)
      in structurally unaffected regions, in particular in the right hemisphere.

PMID- 8994700
TI  - Verb retrieval in aphasia. 2. Relationship to sentence processing.
AB  - Sentence comprehension and production were evaluated for 10 chronic aphasic
      patients who have been shown to demonstrate one of three patterns in the relative
      case of retrieval of nouns and verbs. Although these patterns of noun/verb
      production were not entirely predictable from patients' clinical classifications,
      they were found here to be significantly correlated with several structural
      indices of sentence production and with failure to comprehend semantically
      reversible sentences. Noun/ verb retrieval patterns were not strongly correlated
      with speech fluency nor with morphological characteristics of sentence
      production. Patients with relative impairment in the production of verbs were
      found to rely on high frequency, semantically empty, "light" verbs when producing
      sentences and to favor simple syntactic structures in which verbs do not require
      inflections. When forced to produce substantive verbs (in picture and scene
      descriptions), verb retrieval continued to undermine the production of well
      formed sentences for the verb-impaired patients. In addition, two of five such
      patients also showed some evidence of poor realization of noun arguments for
      verbs they could not produce. Results are interpreted as indicating multiple
      contribution to patients' sentence processing impairments, one of which may be
      selective difficulty retrieving verbs.

PMID- 8994699
TI  - Verb retrieval in aphasia. 1. Characterizing single word impairments.
AB  - The ability of aphasic patients to produce words from the grammatical classes of
      nouns and verbs was investigated in tasks that elicited these types of words in
      isolation. Eleven chronic aphasic patients produced nouns and verbs in picture
      naming, videotaped scene naming, sentence completion, naming from definition, and
      oral reading. Comprehension of the meanings of nouns and verbs was tested in
      word/picture and word/video scene matching, and appreciation of noun/verb
      grammatical class differences was tested with two metalinguistic tasks. Five
      patients demonstrated significantly more difficulty producing verbs than nouns,
      two patients were significantly more impaired producing nouns than verbs, and the
      remaining four patients showed no difference between the two classes. There was
      no improvement in verb production when naming actions presented on videotape,
      suggesting that selective verb impairments are not attributable to conceptual
      difficulty in identifying actions in static pictures. Selective noun impairments
      occurred in the context of severe anomia, as reported in previous studies.
      Selective verb impairments were demonstrated for both agrammatic and fluent
      (Wernicke) patients, indicating that such deficits are not necessarily associated
      with the nonfluent and morphologically impoverished production that is
      characteristic of agrammatism. There was no indication that single word
      comprehension was affected in these patients in a manner consonant with their
      production impairments. Results are interpreted in light of current models of
      lexical organization and processing.

PMID- 8994701
TI  - Judgments of concept similarity by normal and aphasic subjects: relation to
      naming and comprehension.
AB  - A study was conducted in which aphasic patients, age-matched normals, and normal
      young adults performed five types of matching judgments for object pictures.
      These required matching for physical identity, basic object identity, and
      membership in the same superordinate category. Spoken name-to-picture matching
      was tested for the last two conditions. An analogous set of conditions was
      presented for letters. Latency patterns across the conditions showed general
      slowing for the aphasic patients, but with a differential decrement in the
      conditions that involved auditory (spoken name) input for the matching task.
      Results showed that variations in semantic judgment capability among the aphasics
      did not predict the patients' object naming ability.

PMID- 8994702
TI  - Endoscopic and percutaneous intervention in malignant obstructive jaundice.
AB  - Most patients with malignant obstructive jaundice have inoperable disease at
      presentation. There is debate regarding the best approach to palliate these
      patients, i.e., surgical versus endoscopic versus percutaneous drainage. The
      purpose of this article is to review the current literature in an unbiased
      fashion, and to present a rationale for management. A multi-disciplinary approach
      is needed if we are to provide the best care for patients with standardization of
      definitions, complications, and outcomes between specialities such that
      meaningful comparisons can be made between studies. The need for prospective
      randomized trials is clear from the currently deficient literature.

PMID- 8994703
TI  - Sequential transarterial chemoembolization for unresectable advanced
      hepatocellular carcinoma.
AB  - PURPOSE: The aim of this prospective study was to evaluate the feasibility,
      safety, and efficacy of sequential transarterial chemoembolization (TACE) for
      patients with unresectable advanced hepatocellular carcinoma (HCC). METHODS:
      Twenty-one consecutive patients with unresectable T3 and T4 HCC were treated by
      sequential TACE (median time interval between treatments 7 weeks) up to six times
      with an emulsion of lipiodol, epirubicin, and cisplatin. All TACE procedures were
      performed as unilobar or whole-liver chemoembolization. RESULTS: An average of
      3.9 TACE procedures were performed per patient. One primary and two secondary
      technical failures occurred. No procedural death was observed. After exclusion of
      the patient with the primary technical failure and 3 patients with extrahepatic
      disease, the survival rates for the remaining 17 patients at 6, 12, 18, and 24
      months were 70.6%, 52.9%, 44.1%, and 33.1%, respectively. CONCLUSION: Sequential
      TACE is a safe procedure in patients with unresectable advanced HCC and feasible
      in most cases. It seems to prolong the survival time compared with historical
      series of untreated patients.

PMID- 8994704
TI  - Efficacy of Doppler ultrasonography for assessment of transjugular intrahepatic
      portosystemic shunt patency.
AB  - PURPOSE: To assess the efficacy of Doppler ultrasonography (US) as a noninvasive
      method for monitoring patency of the transjugular intrahepatic portosystemic
      shunt (TIPS). METHODS: Twenty-nine patients who had received TIPS for bleeding
      esophagogastric varices and/or refractory ascites with portal hypertension
      underwent Doppler US studies within 2 weeks after TIPS. Further studies were
      performed in 15 of them at 6 months, in 9 at 1 year, and in 4 at 2 years for a
      total of 57 US studies. The US findings were compared with the angiographic
      findings obtained at the same time. RESULTS: In 45 of the 57 studies, shunt
      patency was found by Doppler US, correlating to 44 patencies and one occlusion on
      angiography. Doppler signal in the shunt could not be detected in 12 studies
      resulting in the diagnosis of shunt occlusion. This correlated with angiographic
      occlusion in 8 studies and patency in the remaining 4. All angiographically
      patent shunts that were occluded by Doppler US had various degrees of stenosis. A
      number of technical factors were found to be responsible for Doppler US false
      positive or false-negative diagnoses, some related to the type of stent used. The
      Doppler US sensitivity was therefore 92%, the specificity 89%. CONCLUSION:
      Doppler US is a reliable noninvasive method to evaluate patency of TIPS.

PMID- 8994705
TI  - The use of inferior vena cava filters in pediatric patients for pulmonary embolus
      prophylaxis.
AB  - PURPOSE: To report our experience with inferior vena cava (IVC) filters in
      pediatric patients. METHODS: Over a 19-month period, eight low-profile
      percutaneously introducible IVC filters were placed in four male and four female
      patients aged 6-16 years (mean 11 years). Indications were contraindication to
      heparin in six patients, anticoagulation failure in one, and idiopathic
      infrarenal IVC thrombosis in one. Six of the eight devices placed were titanium
      Greenfield filters. One LGM and one Bird's Nest filter were also placed. Two of
      the filters were introduced via the right internal jugular vein by cutdown, and
      the remainder were placed percutaneously via the right internal jugular vein or
      the right common femoral vein. Patients received follow-up abdominal radiographs
      from 2 to 13 months after IVC filter placement. RESULTS: All filters were
      inserted successfully without complication. Three of the patients died during the
      follow-up period: two due to underlying brain tumors at 2 and 12 months and a
      third at 6 weeks due to progressive idiopathic renal vein and IVC thrombosis. The
      remaining five patients were all alive and well at follow-up without evidence of
      IVC thrombosis, pulmonary emboli, or filter migration. CONCLUSION: IVC filter
      placement using available devices for percutaneous delivery is technically
      feasible, safe, and effective in children.

PMID- 8994706
TI  - Immediate sealing of arterial puncture site following femoropopliteal
      angioplasty: a prospective randomized trial.
AB  - PURPOSE: A new hemostatic puncture closure device (HPCD) was evaluated following
      femoropopliteal angioplasty. Efficacy in hemostasis and complications were
      compared between manual compression and the new system. METHODS: One hundred
      patients undergoing percutaneous interventional procedures were randomly assigned
      to receive either manual compression or HPCD. The time to complete hemostasis
      (when a compression bandage was applied) was noted as well as complications such
      as hematoma or arterial stenosis at the puncture site. Follow-up was by clinical
      examination and color-coded duplex sonography (CCDS). RESULTS: With the HPCD,
      immediate hemostasis was achieved in 22 patients (44%). Discrete oozing without
      the necessity of external compression or further consequences was observed in 11
      patients. Mean manual compression time was 25 (+/- 20) min including application
      of the pressure bandage. Eleven patients needed additional manual compression and
      technical failures were observed in 6 patients (12%). The compression time in
      these 17 cases was 27 (+/- 12) min. Subcutaneous hematomata with a diameter of
      more than 5 cm developed in 15 of 48 patients in the HPCD group and in 14 of 48
      patients in the manual compression group. No surgical or percutaneous
      intervention was necessary. The complication rate was comparably low in the
      experimental and control groups. CONCLUSION: Compared with manual compression
      HPCD is faster and more accurate for sealing the arterial puncture defect
      following angioplasty. After an initial learning curve, it is easy to handle and
      time-saving as well as convenient for the patient. Furthermore, immediate and
      full anticoagulation is possible and arterial inflow is not compromised. A
      drawback is the necessity of an 8 Fr sheath. Nevertheless, the complication rate
      is comparably low for both methods.

PMID- 8994707
TI  - Intraarterial pressure gradients after randomized angioplasty or stenting of
      iliac artery lesions. Dutch Iliac Stent Trial Study Group.
AB  - PURPOSE: To determine initial technical results of percutaneous transluminal
      angioplasty (PTA) and stent procedures in the iliac artery, mean intraarterial
      pressure gradients were recorded before and after each procedure. METHODS: We
      randomly assigned 213 patients with typical intermittent claudication to primary
      stent placement (n = 107) or primary PTA (n = 106), with subsequent stenting in
      the case of a residual mean pressure gradient of > 10 mmHg (n = 45). Eligibility
      criteria included angiographic iliac artery stenosis (> 50% diameter reduction)
      and/or a peak systolic velocity ratio > 2.5 on duplex examination. Mean
      intraarterial pressures were simultaneously recorded above and below the lesion,
      at rest and also during vasodilatation in the case of a resting gradient < or =
      10 mmHg. RESULTS: Pressure gradients in the primary stent group were 14.9 +/-
      10.4 mmHg before and 2.9 +/- 3.5 mmHg after stenting. Pressure gradients in the
      primary PTA group were 17.3 +/- 11.3 mmHg pre-PTA, 4.2 +/- 5.4 mmHg post-PTA, and
      2.5 +/- 2.8 mmHg after selective stenting. Compared with primary stent placement,
      PTA plus selective stent placement avoided application of a stent in 63% (86/137)
      of cases, resulting in a considerable cost saving. CONCLUSION: Technical results
      of primary stenting and PTA plus selective stenting are similar in terms of
      residual pressure gradients.

PMID- 8994708
TI  - Isolated liver perfusion using percutaneous methods: an experimental study in the
      pig.
AB  - PURPOSE: To develop a method for isolated perfusion of the liver using
      radiological methods. METHODS: Twenty-one pigs, weighing about 20 kg, were
      divided into three groups. By transjugular and transfemoral approaches two
      occlusion balloons were placed in the inferior vena cava cranial and caudal,
      respectively, to the origin of the hepatic veins. One occlusion balloon was
      placed transfemorally in the common hepatic artery. Another occlusion balloon was
      inserted in the main branch of the portal vein via the transjugular-transhepatic
      approach in 11 pigs (groups 1 and 2), and in 10 pigs (group 3) by a percutaneous
      transhepatic route. After inflation of the balloons, patency of the isolated
      liver circulation was evaluated by recirculation of 99Tcm-labelled human albumin
      during 30 min. Blood tests were obtained after 1, 3, 5, 10, 15, and 30 min to
      evaluate leakage from the liver to the systemic circulation. RESULTS: Increasing
      leakage to the systemic circulation from the isolated liver circulation was
      observed in groups 1 and 2. In the third group the leakage was less than 10%.
      CONCLUSION: In an experimental animal model, isolated perfusion of the liver with
      minor leakage to the systemic circulation may be achieved using radiological
      methods.

PMID- 8994709
TI  - Local intraarterial thrombolysis: in vitro comparison between automatic and
      manual pulse-spray infusion.
AB  - PURPOSE: Manual and automatic pulse-spray infusion techniques are compared in
      vitro to evaluate the efficacy of thrombolysis and the distribution of urokinase
      and saline solution within thrombus using a pulse-spray catheter. METHODS: A
      pulse-spray catheter was introduced into a human thrombus within a stenotic flow
      model. Automatic and manual pulsed infusion of urokinase and automatic pulsed
      infusion of saline solution were compared. To quantify the efficacy of
      thrombolysis, pressure gradients were recorded proximal and distal to the
      thrombus and during the course of infusion. Distribution of infused urokinase was
      assessed radiographically. RESULTS: The fastest and most homogeneous dissolution
      of the thrombus was achieved with automatic pulsed infusion of urokinase, shown
      by decreasing transthrombotic pressure gradients (p < 0.001, Wilcoxon, matched
      pairs). Manual pulsed infusion of urokinase or saline solution resulted in
      inhomogeneous thrombus dissolution and delayed thrombolysis. CONCLUSION:
      Application of automatic pulse-spray injectors seems beneficial for more
      effective and homogeneous intraarterial pulse-spray thrombolysis when compared
      with conventional manual pulsed technique.

PMID- 8994710
TI  - Contralateral loop snare removal of a ruptured and entrapped angioplasty balloon.
AB  - We describe a technique that extracted a ruptured angioplasty balloon which had
      become entrapped by a calcified left common iliac artery stenosis. The balloon
      catheter had been advanced crossover from the right and could not be retracted
      directly into a sheath across the aortic bifurcation. Therefore, a guidewire was
      inserted through the balloon catheter and captured by a loop snare advanced from
      the left femoral artery. The loop snare was also used to free the balloon wings
      from the stenosis. The balloon was then pulled into a 10 Fr sheath and removed as
      a unit with the sheath.

PMID- 8994711
TI  - Treatment of a ruptured anastomotic esophageal stricture following bougienage
      with a Dacron-covered nitinol stent.
AB  - A patient suffering from esophagorespiratory fistula after bougienage of a benign
      stricture at the site of the anastomosis between a jejunal interposition and the
      esophagus was referred for interventional treatment. A prototype nitinol stent
      centrally covered with Dacron was implanted under regional anesthesia and
      fluoroscopic guidance. The self-expanding prosthesis dilated the stenosis
      completely and closed the fistula, with consequent improvement in respiratory and
      nutritional status and thus the general quality of life. The patient was able to
      eat and drink normally until death 3 months later due to progression of his
      underlying malignant disease.

PMID- 8994712
TI  - Catheter migration of a Port-a-cath system.
AB  - A patient with axillary venous thrombosis caused by lymph node compression and
      the presence of a displaced catheter in the vascular lumen is presented. In this
      case, percutaneous interventional radiological procedures (balloon angioplasty
      and snare loop method) in conjunction with medical treatment were effective in
      limiting the post-thrombotic syndrome and restoring the proper positioning of the
      catheter, thereby saving the central venous access.

PMID- 8994713
TI  - Dissection of retroesophageal aortic diverticulum and descending aorta in a
      patient with right aortic arch: magnetic resonance demonstration.
AB  - An acute aortic dissection involved the retroesophageal aortic diverticulum (RAD)
      and descending thoracic aorta in a patient with right aortic arch. The RAD, which
      was separated into false and true lumens by an intimal flap-the classic
      diagnostic sign of aortic dissection-was overlooked on transesophageal
      echocardiography and computed tomography but was clearly depicted on magnetic
      resonance imaging (MRI). It was found that MRI can delineate the anatomy of a
      congenital arch anomaly complicated by great vessels disease.

PMID- 8994715
TI  - Percutaneous retrieval of a retained Jackson-Pratt drain fragment.

PMID- 8994714
TI  - Transjugular liver biopsy: a review of 77 biopsies using a spring-propelled
      cutting needle (biopsy gun).
AB  - Seventy-seven transjugular liver biopsies were performed with a coaxial, spring
      loaded, 18-gauge cutting needle, the Biopty gun (Bard Biopsy System, Covington,
      GA, USA) on consecutive patients between July 1993 and February 1995. Fifty men
      and 27 women were included in the study; the mean age was 45 years (range 15-69
      years). The average number of punctures per patient was 5.2, with a range of 2-9,
      yielding an average of 4.8 samples per patient (range 1-7). The length of the
      samples varied from 10 to 22 mm with a constant diameter of 1 mm. The mean time
      required to complete the procedure was 48 min (43-52 min). Histological diagnoses
      were obtained in 74 of 77 patients (96%), with non-diagnostic specimens
      attributed to excessive fragmentation (3 cases). Complications occurred in 10
      patients (puncture site hematoma, carotid artery puncture, abdominal pain,
      vasovagal reaction, hepatic capsule perforation, and hemobilia). The latter two
      complications were self-limited. In our experience this transjugular hepatic
      biopsy method is promising for performing biopsies in patients with chronic liver
      disease, due to its high success rate and low morbidity rate.

PMID- 8994716
TI  - Vascular stents and stent grafts: a vascular surgeon's view.

PMID- 8994717
TI  - Influence of radiographic contrast agents on quantitative coronary angiography.
AB  - PURPOSE: Quantitative angiographic studies on the vasomotility of epicardial
      coronary arteries are gaining increasing relevance. We investigated whether
      radiographic contrast agents might influence coronary vasomotor tone and thereby
      the results of such studies. METHODS: Coronary angiograms were taken in 12
      patients with coronary artery disease at intervals of 5, 3, 2, and 1 min with the
      low-osmolar, nonionic contrast agent iopamidol 300, and were repeated at
      identical intervals with the high-osmolar, ionic agent diatrizoate 76%. RESULTS:
      Quantitative cine film analysis demonstrated no significant diameter changes in
      angiographically normal and stenotic coronary arteries with iopamidol. With
      diatrizoate, however, normal segments were dilated 2% +/- 2% (p < 0.01) after 2
      min and 10% +/- 3% after the 1 min interval (p < 0.001). Stenoses showed no
      uniform responses to diatrizoate. CONCLUSION: Low-osmolar, nonionic contrast
      agents should be preferred for quantitative angiographic studies on epicardial
      coronary vasomotility. When using ionic contrast agents, injection intervals of
      at least 3 min are required.

PMID- 8994718
TI  - Results of a multicenter study of the retrievable Tulip Vena Cava Filter: early
      clinical experience.
AB  - PURPOSE: To evaluate clinically a new, retrievable vena caval filter in a
      multicenter study. METHODS: The Tulip filter is a stainless steel half-basket
      that is suitable for antegrade or retrograde insertion via an 8.5 Fr introducer
      sheath. The filter can be retrieved via the jugular approach using an 11 Fr
      coaxial retrieval system. Forty-eight filters were implanted via the femoral
      approach and 38 via the jugular approach in 83 patients. Follow-up examinations
      (plain films, colorcoded duplex sonography) were performed up to 3 years after
      filter insertion (mean 136 days) in 75 patients. Twenty-seven patients were
      screened by colorcoded duplex sonography for insertion site thrombosis. RESULTS:
      An appropriate filter position was achieved in all cases. Insertion problems
      occurred in 3 cases; these were not due to the filter design but to an imperfect
      prototype insertion mechanism that has now been modified (n = 2) or a
      manipulation error (n = 1). In 2 of these cases the filters were replaced
      percutaneously; 1 patient required venotomy for filter removal. No further
      complications due to filter insertion occurred. Two filters were used as
      temporary devices and were successfully removed after 6 and 11 days,
      respectively. There was 1 fatal recurrent pulmonary embolism (PE) and 2 non-fatal
      PE, 5 complete and 3 partial caval occlusions, and 3 caudal migrations of the
      filter. Insertion site venous thrombosis was not seen in the 27 patients
      monitored for this complication. CONCLUSION: Precise placement of the Tulip
      filter is feasible by either access route and the device appears mechanically
      stable. Further observations are needed to confirm that safe filter removal is
      practical up to 10 days after its insertion.

PMID- 8994719
TI  - A comparative analysis of radiological and surgical placement of central venous
      catheters.
AB  - PURPOSE: To compare the differences in practice and outcome of all radiologically
      and surgically placed central venous catheters retrospectively over a 2-year
      period simultaneously, at a single institution. METHODS: A total of 253 Hickman
      catheters were inserted in 209 patients; 120 were placed radiologically in 102
      patients and 133 were placed surgically in 107 patients. The indication was
      chemotherapy in 76% of radiological and in 47% of surgical cases; the remainder
      were for total parenteral nutrition and venous access. RESULTS: There were 6
      (4.5%) primary surgical failures and a further 17 (13%) surgical cases requiring
      multiple placement attempts. Pneumothorax occurred once (0.8%) surgically and
      four times (3.3%) radiologically. There were no radiological primary
      misplacements but there were five (3.7%) surgical ones. Catheter or central vein
      thrombosis occurred in four (3.3%) radiological and five (3.7%) surgical cases.
      The rate of infection per 1000 catheter-days was 1.9 in radiologically placed
      catheters and 4.0 in surgically placed ones (p < 0.001). Average catheter life
      span was similar for the two placement methods (100 +/- 23 days). CONCLUSION:
      Radiological placement is consistently more reliable than surgical placement.
      There are fewer placement complications and fewer catheter infections overall.

PMID- 8994720
TI  - Treatment of hepatocellular carcinoma: a single-center experience.
AB  - PURPOSE: The comparative efficacy of transcatheter arterial chemoembolization
      (TACE) and percutaneous ethanol injection (PEI) in the treatment of
      hepatocellular carcinoma (HCC) was investigated. METHODS: Two hundred and sixty
      consecutive patients were retrospectively analyzed: 156 had received between one
      and six chemoembolization sessions at 3-month intervals, 33 had had PEI, and the
      remaining 71 patients refused any treatment. The follow-up ranged from 3 to 36
      months. Survival rates were statistically analyzed by life-table analysis.
      RESULTS: Patients' survival was affected by the number of nodules and by the
      Child's and Okuda's classes; no relationship was found between survival rates and
      the histologic grade or vascular supply of the tumor. In the case of a single
      lesion of Okuda's class I, TACE was more effective than PEI. In multifocal HCC,
      TACE was better than no treatment in Okuda's class I and Child's class A.
      CONCLUSION: We suggest TACE as the treatment of choice in Child A or Okuda I
      patients with multifocal HCCs; it seems of little help in Child B-C or Okuda II
      III patients.

PMID- 8994721
TI  - Transjugular intrahepatic portosystemic shunting (TIPS) with balloon-expandable
      and self-expanding stents: technical and clinical aspects after 3 1/2 years'
      experience.
AB  - PURPOSE: To evaluate prospectively our experience with transjugular intrahepatic
      portosystemic shunt (TIPS) using four different metallic stents. METHODS: Between
      November 1991 and April 1995, 57 patients (41 men and 16 women; age 35-72 years,
      mean 54 years) underwent the TIPS procedure. Techniques for portal vein
      localization before and during TIPS were fluoroscopy, computed tomography (CT)
      studies, wedged hepatic venography, arterial portography, and ultrasound. After
      predilation we deployed balloon-expandable (n = 48) and self-expanding (n = 45)
      metallic stents. Fifteen patients underwent variceal embolization. Initial follow
      up angiograms (mean 6.9 months, range 3-24 months) were obtained in 39 of these
      patients. RESULTS: Fifty-three patients (93%) had successful TIPS placement. The
      mean decrease in portal pressure was 42.7%. Besides fluoroscopy, the most helpful
      techniques for portal vein localization were venography and CT. Residual stenosis
      (n = 1) and late shortening (n = 4) of Wallstents resulted in shunt dysfunction.
      The technical problems encountered with the Palmaz stent resulted from its lack
      of flexibility. We combined balloon-expandable and self-expanding stents in 12
      patients. The 30-day and late follow-up (mean 11.9 months) percutaneous
      reintervention rates were 11.3% and 64.2%, respectively. There were no clinically
      significant complications related to the TIPS insertions. CONCLUSION: An ideal
      stent does not exist for TIPS, and the authors recommend combining a Palmaz stent
      with a flexible self-expanding stent.

PMID- 8994723
TI  - Metallic stents in malignant biliary obstruction.
AB  - PURPOSE: Retrospective analysis of our results with metallic stent placement for
      malignant biliary strictures. We sought to determine parameters that influence
      stent patency. METHODS: A total of 95 Wallstents were implanted in 65 patients
      (38 men, 27 women; mean age, 65.1 years) with malignant biliary obstruction.
      Serum bilirubin levels were assessed in 48 patients; the mean value prior to
      intervention was 15.0 mg/dl. RESULTS: In 12 patients (21%) complications occurred
      as a result of percutaneous transhepatic drainage. Stent implantation was
      complicated in 13 patients, but was possible in all patients. A significant
      decrease in bilirubin level was seen in 83.3% of patients following stent
      implantation. Approximately 30% of patients developed recurrent jaundice after a
      mean 97.1 days. In 9 patients (15%) the recurrent jaundice was caused by stent
      occlusion due to tumor growth. The mean follow-up was 141.8 days, the mean
      survival 118.7 days. Patients with cholangiocarcinomas and gallbladder carcinomas
      had the best results. Worse results were seen in patients with pancreatic tumors
      and with lymph node metastases of colon and gastric cancers. CONCLUSIONS: The
      main predictive factors for occlusion rate and survival are the type of primary
      tumor, tumor stage, the decrease in bilirubin level, and the general condition of
      the patient.

PMID- 8994722
TI  - Is the tantalum Strecker stent suitable for TIPS creation? Short- and mid-term
      results in 20 consecutive patients.
AB  - PURPOSE: To assess the suitability of tantalum Strecker stents for transjugular
      intrahepatic portosystemic shunt (TIPS) creation. METHODS: TIPS was performed
      with Strecker balloon-expandable stents in the first 20 patients of our series. A
      total of 26 prostheses were utilized (average 1.3 per patient). RESULTS:
      Immediate technical success was achieved in all 20 cases. Nine patients (45%)
      died during follow-up. The overall average follow-up period was 18.9 months; the
      11 survivors were followed for a mean period of 29.8 months. In 4 patients (20%)
      the stent dislodged towards the hepatic vein during withdrawal of the balloon
      catheter, and difficulties in recatheterizing the shunt for routine control
      portal phlebography were frequently encountered. Rebleeding occurred in 5 cases
      and aggravation of pre-existing encephalopathy occurred in 2 cases. Shunt
      occlusions or stenosis required further intervention in 4 and 9 patients,
      respectively. CONCLUSION: In our opinion the tantalum Strecker stent is not
      particularly suitable for TIPS. Although it has evident advantages, such as high
      radiopacity and minimal shortening after deployment, the tendency of the device
      to dislodge and the difficulty in recatheterization during portal phlebography
      were important drawbacks. Furthermore, the atraumatic ends of the device did not
      seem to reduce shunt-related complications, which were comparable to those
      occurring with other types of stent.

PMID- 8994724
TI  - Dependency of tissue necrosis on gelatin sponge particle size after canine
      hepatic artery embolization.
AB  - PURPOSE: To determine the optimal size of gelatin sponge particles (GSPs) to
      produce maximum tumor necrosis with minimum side effects after canine hepatic
      artery embolization (HAE). METHODS: GSPs were separated into four size ranges: A,
      up to 200 microns (mean 152) as Gelfoam powder; B, 200-500 microns (mean 336) as
      Gelfoam powder; C, 500-1000 microns (mean 649) as Spongel; and D, 1000-2000
      microns (mean 1382) as Spongel. Three mongrel dogs were assigned randomly to HAE
      with each particle size. On day 7 after HAE, the livers were removed and
      subjected to pathological examination. RESULTS: The mean volume of liver necrosis
      was 11% after embolization, with particle size A, 36.3% with B, 0% with C, and 1%
      with D. Coagulation necrosis was found in all livers with particles of sizes A
      and B, and in 1 of 6 with sizes C and D. Bile duct injury was found in five of
      six dogs with sizes A and B and in none with sizes C and D. Gallbladder necrosis
      was found in one dog with size B and pancreas necrosis in one with size A.
      CONCLUSION: GSPs of 500 microns are considered optimally effective for tissue
      necrosis according to this model.

PMID- 8994726
TI  - Popliteal artery thrombosis in a patient with Cogan syndrome: treatment with
      thrombolysis and percutaneous transluminal angioplasty.
AB  - A 31-year-old woman with Cogan syndrome (a rare form of systemic vasculitis) was
      evaluated for a cold, painful left foot with diminished pulses. Arteriography
      demonstrated thrombosis of the left popliteal artery with evidence of vasculitis.
      Thrombolytic therapy was begun with initial success but eventual rethrombosis.
      After reinitiating thrombolytic therapy combined with intraarterial vasodilator
      therapy, successful angioplasty was performed with sustained results at 6-month
      follow-up.

PMID- 8994725
TI  - Arteriovenous fistula at the site of balloon dilatation complicating
      femoropopliteal angioplasty.
AB  - We describe an arteriovenous fistula (AVF) at the site of balloon dilatation
      immediately after percutaneous transluminal angioplasty (PTA) of the
      femoropopliteal artery. This occurred during an otherwise uncomplicated
      angioplasty with a good clinical result. The AVF closed spontaneously within 2
      months as monitored by color duplex ultrasound. This uncommon complication of PTA
      is not widely recognized.

PMID- 8994727
TI  - Partially covered Gianturco stent for tracheobronchial stricture caused by
      intraluminal tumor.
AB  - Partially covered Gianturco stents were used successfully in two patients to
      treat tracheobronchial strictures caused by intraluminal tumor growth. The stents
      were accurately placed without complications. The covered portion of the stent
      compressed the tumor, and prevented tumor ingrowth until the patients' deaths.
      This stent seems to act as effective palliation for tracheobronchial stricture
      caused by intraluminal tumor.

PMID- 8994728
TI  - Treatment of a malignant esophageal fistula with a Gore-Tex-covered flexible
      nitinol stent.
AB  - In order to treat fistulated esophageal cancer using a flexible stent, a covered
      flexible stent was constructed by wrapping a nitinol stent with a thin sheet of
      Gore-Tex, preserving the stents original advantages of flexibility and a low
      profile introducer system. This stent was used to perform standard radiotherapy
      in a case of fistulated esophageal cancer.

PMID- 8994729
TI  - Advertising of therapies for cardiovascular patients.

PMID- 8994730
TI  - Angiotensin-II-receptors: new targets for antihypertensive therapy.
AB  - The renin-angiotensin system regulates blood pressure and sodium homeostasis
      through a series of coordinated substrate-enzyme interactions. These interactions
      result in the production of angiotensin II (AII), which exerts a number of
      diverse biologic effects mediated through AII cell-surface receptors.
      Dysregulation of this system is implicated in the pathogenesis of various forms
      of hypertension. Traditional therapy for hypertension has included angiotensin
      converting enzyme inhibitors, which block the production of AII. However, a new
      class of drugs, AT1-receptor blockers, now offers a number of benefits by
      specifically blocking the effects of AII at its physiologically relevant
      receptor.

PMID- 8994731
TI  - Biochemical markers of coagulation activation in mitral stenosis, atrial
      fibrillation, and cardiomyopathy.
AB  - Advances in the understanding of the biochemistry of the mechanism of hemostasis
      have led to the development of sensitive methods for determining levels of
      markers which reflect thrombin activity (thrombin-antithrombin III complex,
      fibrinopeptide A, F1 + 2 fragment), active fibrinolysis (D-dimer, plasmin-alpha 2
      plasmin inhibitor complex), and platelet activity (platelet factor 4, beta
      thromboglobulin) in vivo. Measurement of these markers may be useful in
      identifying patients with various cardiovascular disorders at high risk of
      thromboembolism.

PMID- 8994732
TI  - Variability in the measurement of intracoronary ultrasound images: implications
      for the identification of atherosclerotic plaque regression.
AB  - BACKGROUND AND HYPOTHESIS: Serial coronary angiography cannot reliably detect the
      small changes in arterial dimensions. Measurement of arterial dimensions by
      intracoronary ultrasound (ICUS) may be a superior method to determine the extent
      of atherosclerotic burden since it directly images the diseased portion of the
      vessel. METHODS: To quantify inter- and intraobserver variability of ICUS
      measurements, 27 images of atherosclerotic coronary lesions were measured by two
      study physicians and repeated 14 days later. RESULTS: Interobserver correlation
      coefficients for external elastic lamina, lumen, and effective plaque area were
      0.96, 0.99, and 0.91, respectively. Intraobserver correlation coefficients for
      external elastic lamina, lumen, and effective plaque area were 0.99, 0.99, and
      0.97, respectively. To determine progression or regression in effective plaque
      area, a minimal difference of 2.77 mm2 (which represents a 23% change in plaque
      area) is needed. CONCLUSIONS: Direct visualization of the extent of
      atherosclerosis by ICUS can be accomplished with a low degree of inter- and
      intraobserver variability. ICUS may be a preferable alternative to angiography in
      atherosclerosis regression trials.

PMID- 8994733
TI  - Abnormal signal-averaged electrocardiograms in patients with incomplete right
      bundle-branch block.
AB  - BACKGROUND AND HYPOTHESIS: A hypothesis was formulated that regional delayed
      activation of the right ventricle, as seen in incomplete right bundle-branch
      (IRBBB) aberrancy, may simulate late potential activity and may be responsible
      for abnormal signal-averaged electrocardiograms (SAECGs). No previous studies
      have specifically addressed this issue in this particular group of patients (with
      IRBBB). Therefore, the aim of the present study was to investigate the incidence
      of abnormal SAECGs in patients with IRBBB. If this were confirmed, our purpose
      would further be to investigate ways of reducing the false positive results.
      METHODS: The study group included 53 patients (28 men and 25 women), aged 53 +/-
      13 years, with no history of previous myocardial infarction or ventricular
      tachycardia and who had an electrocardiogram (ECG) showing IRBBB. An SAECG was
      also performed in a control group of 19 age-matched individuals with a normal
      ECG. Time domain analysis was performed using a band pass filter of 40-250 Hz.
      The following parameters were considered normal: filtered QRS duration (QRSD) <
      114 ms, root mean square of the voltage of the last 40 ms of the QRS complex
      (RMS) > 20 microV, and the duration of the low amplitude signal (< 40 microV) at
      the terminal portion of the QRS (LAS) < 38 ms. An SAECG was considered abnormal
      if any two of these criteria were abnormal. RESULTS: The mean values of the SAECG
      parameters were: QRSD 101 +/- 11 ms, RMS 32 +/- 20 microV, LAS 32 +/- 12 ms, and
      noise 0.29 +/- 0.13 microV. Abnormal SAECGs with at least two criteria satisfied
      were present in 16 of 53 (30%) patients compared with 0 (0%) of 19 individuals in
      the control group (p = 0.02). Abnormal values included the combination of RMS and
      LAS in 12 patients and all three parameters in 4 patients. However, if the
      definition of late potentials were limited to the combination of abnormal QRSD
      and either RMS or LAS values, the incidence of false positive results (4
      patients) (7.5%) would be significantly decreased (p = 0.007). At 21 months of
      follow-up, no arrhythmic events occurred. CONCLUSIONS: Delayed terminal
      conduction observed in IRBBB may cause a high incidence of false positive late
      potentials on SAECGs. Based on this study, we propose that this can be largely
      remedied if the optimal criteria for the presence of late potentials in patients
      with IRBBB always include the combination of QRSD and either RMS or LAS.

PMID- 8994734
TI  - The effect of atrial fibrillation and the ventricular rate control on exercise
      capacity.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia, affecting
      approximately 1.5 million patients in the United States. HYPOTHESIS: This study
      was designed to determine the effect of AF and the ventricular rate control
      during AF on cardiovascular performance as measured by exercise endurance on a
      standard Bruce protocol. METHODS: Sixty-three patients with AF who underwent
      exercise stress testing during both sinus rhythm and AF were analyzed. Heart
      rate, blood pressure, heart rate acceleration, exercise duration, and left
      ventricular (LV) systolic function were measured. RESULTS: Atrial fibrillation
      resulted in a small but statistically significant decrease in exercise endurance
      (426 +/- 180 vs. 402 +/- 168 s, p < 0.05). The drop in exercise tolerance was
      consistent regardless of the underlying heart condition or adequate ventricular
      rate control during AF. Heart rate in AF was consistently faster than in sinus
      rhythm, at rest, and at peak exercise (63 vs. 79 beats/min and 125 vs. 149
      beats/min, respectively, p < 0.001). CONCLUSION: Our analyses indicated that (1)
      the loss of atrioventricular synchrony had minimal effect on cardiovascular
      performance in patients with preserved LV function, (2) the decrease in
      cardiovascular performance was related to loss of atrioventricular synchrony but
      not to underlying heart disease or ventricular rate control, and (3) compensation
      for the loss of the atrial contribution was provided by consistently faster heart
      rate during AF.

PMID- 8994735
TI  - Early predictors of late dilation and remodeling after thrombolized anterior
      transmural myocardial infarction.
AB  - BACKGROUND AND HYPOTHESIS: Dilation of the left ventricle after myocardial
      infarction is associated with an adverse prognosis. There are no clinical studies
      on the role viable myocardium in the infarcted area assumes in relation to the
      development of late ventricular remodeling. The hypothesis of this study was to
      define the relation between remodeling and the presence of viable but akinetic
      myocardium in the infarct area and to identify early predictors of left
      ventricular (LV) dilation at 1 year. METHODS: In all, 92 consecutive patients
      with myocardial infarction were divided into two groups according to their
      ventricular volumes. Group I included 57 patients with normal volumes at
      discharge (9 +/- 3 days after acute infarction) and after 12 months or with LV
      dilation at discharge who had a normalization of their volumes over a 12-month
      period. Group II included 35 patients who, independent of their initial volumes,
      developed LV dilation during follow-up. Low-dose dobutamine infusion was utilized
      at discharge for echocardiographic evaluation of contractile recovery of viable
      myocardial segments. RESULTS: At the first control, patients in Group I presented
      an end-diastolic volume index (EDVI) of 100 +/- 7 ml/m2 which decreased to 68.8
      +/- 6.5 ml/m2 12 months later (p < 0.0001), and an end-systolic volume index
      (ESVI) of 47.6 +/- 6.7 ml/m2 at the first control and 30.5 +/- 8.8 ml/m2 after 12
      months (p < 0.001). Patients in Group II presented a mean EDVI of 116.2 +/- 8.1
      ml/m2 at the first control and 138.8 +/- 8 ml/m2 12 months later (p < 0.001), and
      a mean ESVI of 68.8 +/- 6.5 ml/m2 at the first control and 79.5 +/- 5.4 after 12
      months (p < 0.01). Ventricular mass index (VMI) in Group I increased from 106.4
      +/- 11 to 122.3 +/- 15 g/m2 (p < 0.01), while in Group II it decreased from 101.1
      +/- 10 to 98.7 +/- 8 g/m2 (p = NS). In Group I, mass-to-volume ratio was 1.15 +/-
      0.1 g/ml at the first control and 1.67 +/- 0.1 g/ml 12 months later (p < 0.001),
      while in Group II it declined from 0.88 +/- 0.1 to 0.69 +/- 0.1 g/ml (p < 0.01).
      The multivariate analysis revealed that ejection fraction < or = 40%, restrictive
      filling pattern, wall motion score index > 2.5 in response to dobutamine
      infusion, and mass-to-volume ratio < or = 1 g/ml, all at discharge, as well as an
      occluded left anterior descending artery discriminate in favor of late LV
      dilation and remodeling. CONCLUSIONS: Correct use of noninvasive strategies
      should result in early identification of postinfarct patients who are at risk of
      developing LV remodeling.

PMID- 8994736
TI  - Retrograde atrial kick in acute aortic regurgitation. Study of mitral and
      pulmonary venous flow velocities by transthoracic and transesophageal
      echocardiography.
AB  - BACKGROUND AND HYPOTHESIS: The purpose of this study was the comprehensive
      evaluation of the changes in pulmonary venous and mitral flow velocities of
      patients with acute and chronic severe aortic regurgitation. Transmitral flow
      velocities obtained with pulsed-wave Doppler echocardiography have been used to
      provide information on left ventricular (LV) filling and diastolic function.
      Pulmonary venous flow tracings are an important adjunct to LV inflow pattern in
      assessing LV diastolic function. METHODS: Fourteen patients with severe aortic
      regurgitation (8 chronic and 6 acute) and in sinus rhythm were examined by
      transthoracic and transesophageal pulsed Doppler echocardiography. Mitral and
      pulmonary flow velocities were recorded and compared. All patients had ejection
      fractions > 40%. RESULTS: Early mitral flow peak velocity was higher in patients
      with acute regurgitation (p < 0.001). The mitral A wave was absent in five
      patients with acute regurgitation. In contrast, a prominent reverse atrial
      pulmonary systolic wave AR was demonstrated in these patients. Peak diastolic
      velocity of the pulmonary venous flow was greater in patients with acute aortic
      regurgitation (0.76 +/- 0.13) than in patients with chronic aortic regurgitation
      (0.40 +/- 0.09) (p < 0.001). Peak systolic velocity did not differ significantly
      between the two groups. The systolic fraction of pulmonary venous flow in
      patients with acute aortic regurgitation was lower (0.43 +/- 0.05) than that of
      patients with chronic regurgitation (0.63 +/- 0.1) (p < 0.01). All patients with
      acute aortic regurgitation had an S/D ratio < 1, while those with chronic
      regurgitation had an S/D > 1 (p < 0.001) and an E/A < 1. CONCLUSION: Patients
      with severe acute aortic regurgitation showed a retrograde atrial kick (absence
      of transmitral A wave with prominent pulmonary AR wave). These patients had an
      S/D ratio < 1 (restrictive Doppler pattern). Patients with chronic aortic
      regurgitation exhibited a Doppler pattern of abnormal LV relaxation (E/A < 1, S/D
      > 1).

PMID- 8994737
TI  - High-rate cardiac pacing increases blood pressure and decreases right atrial
      pressure in patients with hemodynamic significant acute right ventricular
      myocardial infarction and bradyarrhythmia.
AB  - BACKGROUND: In an 84-year-old patient with acute right ventricular myocardial
      infarction (RVI), complete heart block, and low cardiac output, a significant
      increase in blood pressure (BP) and decrease in right atrial pressure (RAP) were
      accidentally observed during the performance of high-rate ventricular pacing.
      METHODS: Based on that observation, the acute effects of high-rate cardiac pacing
      (VVI or AAI) on BP and RAP were studied in 15 consecutive patients (67.4 +/- 7.7
      years), with hemodynamically significant RVI. Ten had advanced heart block and
      five had sinus bradycardia. Cardiac pacing with simultaneous recording of BP and
      RAP at intrinsic rhythm and at heart rates of 70, 90, 110, 130 beats/min was
      performed. RESULTS: Systolic BP (SBP) increased significantly from 94.6 +/- 15
      mmHg during intrinsic rhythm to 101.9 +/- 13.8 mmHg-127 +/- 12.2 mmHg at heart
      rates 70-130 beats/min (p < 0.0001). Diastolic BP (DBP) also increased from 48.2
      +/- 8.7 to 53.9 +/- 3.7-69.1 +/- 3 mmHg at heart rates 70-130 beats/min, (p <
      0.014-0.0001). Mean RAP decreased from 14.5 +/- 5 to 14.1 +/- 5 mmHg-11.1 +/- 4.1
      mmHg at heart rates 70-130 beats/min (p = 0.16-0.0001). Significant elevation of
      SBP (p < 0.007), DBP (p < 0.0075), and decrease of RAP (p < 0.038) were also
      detected by comparing the usual pacing rate at 70 beats/min with pacing rates at
      90-130 beats/min. CONCLUSIONS: These findings, if demonstrated over a prolonged
      period during the acute state of RVI, may influence the management of patients
      with RVI to include high-rate cardiac pacing, probably in the range of 80-110
      beats/min.

PMID- 8994738
TI  - Transesophageal pulsed Doppler echocardiographic evaluation of left atrial
      systolic performance in hypertrophic cardiomyopathy: combined analysis of
      transmitral and pulmonary venous flow velocities.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HC) is characterized by impaired left
      ventricular (LV) diastolic function due to an increase in LV wall thickness. The
      severity of this disease varies depending on the localization and extent of the
      hypertrophied myocardium and the presence and extent of myocardial disarray or
      fibrosis. HYPOTHESIS: The purpose of this study was to examine the background of
      hemodynamic abnormalities between the left atrium and the left ventricle during
      atrial systole in patients with HC using pulsed Doppler echocardiography.
      METHODS: Hemodynamic abnormalities between the left atrium and left ventricle
      during atrial systole were evaluated in patients with HC using transmitral flow
      (TMF) and pulmonary venous flow (PVF) velocities obtained by transesophageal
      pulsed Doppler echocardiography. The study population included 50 patients with
      HC, including 39 with asymmetric septal hypertrophy and 11 with apical
      hypertrophy, and showing fractional shortening of the left ventricle > or = 30%.
      They were classified into three groups: (1) Group A (n = 11): the ratio of the
      late to early TMF velocity < 1, and peak atrial systolic PVF velocity (PVA) < 25
      mm/s; (2) Group B (n = 13): their ratio < 1, and PVA > or = 25 mm/s; and (3)
      Group C (n = 26): their ratio > or = 1. The mean age of patients in Group A was
      lower than that in Groups B and C. RESULTS: Left atrial dimension in Group B was
      significantly greater than that in the other HC groups and the control group.
      Furthermore, left atrial volume changes during atrial systole in Group B were
      significantly smaller than those in the other HC groups and the control group.
      Peak atrial systolic PVF velocity in Group B was significantly higher than that
      in the control group and in Group C. The duration of the atrial systolic waves of
      the TMF and PVF in Group B was significantly shorter and longer, respectively,
      than that in Group A. Left ventricular end-diastolic pressure (LVEDP) decreased
      in descending order with Group B > Group C > Group A. In all patients there was a
      significant positive correlation between the LVEDP and peak atrial systolic PVF
      velocity or the difference in duration between the atrial systolic waves of PVF
      and TMF. Plots of these values shifted toward the left and inferiorly in Group A,
      and toward the right and superiorly in Group B. CONCLUSION: Peak velocity and
      duration of TMF and PVF during atrial systole by transesophageal pulsed Doppler
      echocardiography are useful indices of hemodynamic abnormalities between the left
      atrium and the left ventricle during atrial systole, particularly a forceful
      atrial contraction mismatched to the left atrial afterload and severity of LV
      diastolic dysfunction, in HC.

PMID- 8994739
TI  - Creatine kinase isoforms as circulating markers of deterioration in idiopathic
      dilated cardiomyopathy.
AB  - BACKGROUND: A proportion of patients with dilated cardiomyopathy (DCM) may have
      ongoing myocardial damage secondary to viral or immune mediated myocardial
      inflammation. HYPOTHESIS: The prognostic determinants identify patients with
      decreased survival but do not provide a measure of myocardial damage. To obtain
      an objective assessment of myocardial damage in DCM, we measured plasma levels of
      creatine kinase (CK), its isoenzymes (CK-MM and CK-MB), and separated the
      isoforms of CK-MM and CK-MB. METHODS: The cohort consisted of 77 consecutive
      patients (61 men, 16 women) with DCM (World Health Organization criteria), aged
      49 +/- 14 years (range 19-60). Patients had been symptomatic for 29 +/- 38 months
      (range 0.5-200 months) with 48 in New York Heart Association class I/II and 29 in
      class III/IV at the time of diagnosis. During median follow-up of 27 months from
      diagnosis (range 0.6-165), 50 patients remained clinically stable and 27 had
      deteriorated. RESULTS: A significantly higher proportion of patients with DCM had
      abnormal MB2/MB1 ratio compared with normal volunteers (11, 14% vs. 1,1%, p =
      0.003). Patients who deteriorated had higher MB2/MB1 ratio, (1.22 +/- 0.62 vs.
      0.85 +/- 0.56; p = 0.01), and more frequently had abnormal MB2/ MB1 ratio (8, 30%
      vs. 3, 6%; p = 0.004) and CK and CK-MM activities (5, 19% vs. 2, 4%; p = 0.03)
      than those who remained stable. Patients with DCM with high CK-MB activity had
      3.13-fold increased odds of sudden death or need for cardiac transplantation (95%
      confidence interval 1.53-6.40, p = 0.008). Thus, CK measurements, in particular
      CK-MB isoforms, are markers of myocardial damage in a subset of patients with DCM
      and could be useful in investigating the possibility of persistent myocardial
      damage in these patients.

PMID- 8994740
TI  - Relation of iodine-123 metaiodobenzylguanidine myocardial scintigraphy to
      endomyocardial biopsy findings in patients with dilated cardiomyopathy.
AB  - BACKGROUND: Iodine-123 metaiodobenzylguanidine (123I-MIBG) concentrates in
      adrenergic neurons and has been developed for evaluation of the sympathetic
      nervous system. Recent studies have demonstrated that the normal heart is clearly
      visualized by 123I-MIBG cardiac scintigraphy, whereas abnormal 123I-MIBG
      myocardial uptake and washout have been demonstrated in patients after myocardial
      infarction and in patients with congestive cardiomyopathy, long QT syndrome, and
      ventricular tachycardia. HYPOTHESIS: Based on evidence from recent studies, it
      can be hypothesized that 123I-MIBG uptake is related to histopathologic changes
      in the myocardium. METHODS: The relation of 123I-MIBG uptake to the histologic
      findings for the heart was studied in 24 patients with dilated cardiomyopathy
      (DCM). The study group did not include patients with complicating disorders that
      primarily affect the adrenergic nervous system. The 123I-MIBG uptake was visually
      assigned one of four grades using the two criteria of the mean score for six
      regional uptake grades (mean score) and the global score obtained by visual
      evaluation of the entire image (global score). The 123I-MIBG uptake score was
      also determined for the region at which the biopsy specimen was obtained (biopsy
      region score). The histologic findings were evaluated by assigning one of four
      grades for each of the following five factors: myocyte hypertrophy, myocardial
      fibrotic change, myocyte degeneration and necrosis, mononuclear cell
      infiltration, and myocyte disarray. The sum for all grades was defined as the
      total score, and the global score was also assigned to the overall histologic
      findings. RESULTS: All of the global, mean, and biopsy region scores for 123I
      MIBG uptake correlated significantly with the global and total scores for the
      histologic findings. Among the histologic factors, myocyte degeneration showed
      score correlated with all global, mean, and biopsy region scores for the uptake.
      Myocyte hypertrophy was associated weakly with the 123I-MIBG uptake scores.
      CONCLUSION: These results indicate that 123I-MIBG uptake imaging is associated
      with histopathologic abnormalities in patients with DCM.

PMID- 8994741
TI  - Coronary artery and saphenous vein graft remodeling: a review of histologic
      findings after various interventional procedures--Part V.
AB  - Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of
      acutely and chronically obstructed coronary artery vessels. It is also the
      centerpiece for various new intervention techniques. Their morphologic effect on
      the site of obstruction has been termed "remodeling." Part V of this six-part
      series focuses on remodeling effects of balloon angioplasty on obstructed young
      (< or = 1 year) and old (> 1 year) saphenous vein bypass grafts.

PMID- 8994742
TI  - Unmasking of fast and slow atrioventricular nodal pathways by successful
      radiofrequency ablation of two accessory atrioventricular connections.
AB  - Electrophysiologic findings suggesting the coexistence of dual atrioventricular
      (AV) nodal pathways and accessory AV connections have been previously described.
      Anterograde conduction through the accessory pathway (AP) may preclude the
      diagnosis of AV nodal dual pathway physiology during atrial stimulation. This
      study reports on a patient with manifest Wolff-Parkinson-White syndrome with
      clinically documented paroxysmal atrial fibrillation, in whom dual AV nodal
      pathways were unmasked after successful radiofrequency ablation of two accessory
      AV connections. In spite of detailed investigation, fast and slow AV nodal
      pathways were not detected in the first electrophysiologic study 8 years before
      ablation, nor were they detected during preablation study because of exclusive
      anomalous anterograde conduction. The anterograde AP effective refractory period
      was shorter than that of the fast and slow AV nodal pathways, and was limited by
      atrial refractoriness at 190 ms. The present findings strongly suggest the
      necessity for a careful postablation eletrophysiologic study before and after
      isoproterenol administration with specific evaluation of AV nodal conduction.
      This is the first documented report on the finding of AV nodal dual pathway
      physiology and reentry after successful radiofrequency ablation of two APs. This
      finding may be of great therapeutic significance in light of the feasibility of
      slow pathway ablation also during a single session, had AV nodal reentry been
      induced in a sustained manner after ablation of the AP to prevent late recurrence
      of tachycardia.

PMID- 8994743
TI  - Paracardiac masses caused by a right coronary artery aneurysm and a saphenous
      vein graft aneurysm.
AB  - Two unusual cases of large aneurysms, one located in the native right coronary
      artery and the other in a saphenous vein graft, are reported. Their size and mode
      of presentation as asymptomatic paracardiac masses on chest x-ray films make them
      unique. It is proposed that these entities be considered as part of the
      differential diagnosis of paracardiac masses.

PMID- 8994744
TI  - Dynamic three-dimensional echocardiography in the assessment of cor triatriatum.
AB  - Classic cor triatriatum sinistrum is a rare cardiac malformation to be found in
      the adult. One year after surgical correction of an atrial septal defect in a 55
      year-old man, cor triatriatum sinistrum was diagnosed by transesophageal
      echocardiography. We compared transthoracic echocardiography, transesophageal
      echocardiography, and cardiac catheterization to dynamic three-dimensional
      echocardiography (3-D echo) which offers a new, noninvasive approach to determine
      the opening size between the accessory and the true left atrium. The findings by
      3-D echo, confirmed by left heart catheterization, showed that the accessory
      membrane was not stenosing. Surgical correction was therefore not indicated in
      this patient.

PMID- 8994745
TI  - Unsuspected vasculitis and intracranial hemorrhage following thrombolysis.
AB  - Treatment with thrombolytic agents such as streptokinase or tissue plasminogen
      activator (TPA) is an accepted standard for the treatment of patients with acute
      myocardial infarction (MI). A devastating sequel of thrombolytic therapy may be
      the development of a hemorrhagic complication, particularly intracranial
      bleeding, which, although rare, is usually associated with significant neurologic
      sequelae or death. While various risk factors have been correlated with the
      development of intracranial hemorrhage following thrombolysis, a possible
      relationship between bleeding and a clinically unsuspected underlying vasculitis
      has not been previously reported. This report deals with the case of a 49-year
      old man who died of multiple intracranial hemorrhages after thrombolytic therapy
      for acute MI and who was found at autopsy to have had polyarteritis nodosa of the
      coronary arteries and vasculitis of the meningeal vessels.

PMID- 8994746
TI  - Thomas Young.

PMID- 8994747
TI  - Listeriosis.

PMID- 8994749
TI  - Photo quiz. Blepharitis due to herpes simplex virus type 1.

PMID- 8994748
TI  - Detection of enterotoxigenic Bacteroides fragilis and its toxin in stool samples
      from adults and children in Italy.
AB  - Stool samples from children and adults with and without diarrhea were examined
      for the presence of enterotoxigenic Bacteroides fragilis (ETBF) and its
      enterotoxin. A cytotoxic assay with HT-29 cells followed by neutralization with a
      hyperimmune antiserum were used to detect B. fragilis enterotoxin. ETBF isolates
      were recovered from 12% of healthy children and 17% of children with diarrhea (P
      = .42) and from 15% of healthy adults and 9.4% of adults with diarrhea (P = .31).
      Fecal B. fragilis enterotoxin was detected in four children (two with diarrhea
      and two without diarrhea) and in four adults with diarrhea. This study shows that
      in Italy, the rate of ETBF carriage is high, regardless if diarrhea is present.
      In some instances, the presence of ETBF is associated with detectable levels of
      fecal enterotoxin, but the significance of this finding deserves further
      evaluation.

PMID- 8994750
TI  - Infectious complications in left ventricular assist device recipients.
AB  - The left ventricular assist device (LVAD) has revolutionized the care of patients
      with heart failure who are awaiting transplantation. Despite reports of
      significant infection rates associated with LVAD implantation, few data are
      available concerning the management of LVAD-related infections and their impact
      on transplantation. Eight (40%) of our first 20 LVAD recipients developed
      infections. LVAD-related bloodstream infection occurred in three (15%) patients;
      infection was due to Staphylococcus aureus in one case, coagulase-negative
      staphylococci in the second case, and S. aureus and Candida tropicalis in the
      third case. All three patients were treated with courses of antibiotics that were
      appropriate for prosthetic valve endocarditis and received antibiotics for at
      least 6 weeks. All infected patients underwent successful transplantation and had
      no evidence of recurrence of infection up to 16 months postoperatively. Our
      experience suggests that LVAD infections can be successfully treated without
      device removal and that cardiac transplantation can be performed in individuals
      with LVAD-related bloodstream infection.

PMID- 8994751
TI  - Congenital syphilis: detection of Treponema pallidum in stillborns.
AB  - Paraffin-embedded tissue from all 17 autopsies performed following 56 stillbirths
      associated with maternal syphilis during a 3-year period (1987-1989) was
      reexamined to compare immunofluorescent antigen (IFA) testing with silver
      staining for the detection of Treponema pallidum. Congenital syphilis (CS)
      originally was diagnosed in 9 of the 17 cases of stillbirth, on the basis of
      positive silver stains (7 cases) or morphological findings alone (2). Upon
      review, silver staining revealed T. pallidum in 10 of 17 cases and IFA testing
      revealed the pathogen in 15 of 17 cases, enabling diagnosis of CS in 16 of 17
      cases of stillbirth associated with a reactive maternal rapid plasma reagin (RPR)
      card test. Most stillbirths associated with a reactive maternal RPR test during
      this time period involved CS, and IFA testing for T. pallidum is superior to
      silver staining for the identification of treponemes.

PMID- 8994752
TI  - Infection due to fluconazole-resistant Candida in patients with AIDS: prevalence
      and microbiology.
AB  - A cross-sectional study was conducted to assess the prevalence and microbiology
      of oral infection due to fluconazole-resistant Candida in patients with AIDS.
      Oral swab specimens for fungal cultures were obtained from 100 consecutive
      outpatients with CD4 lymphocyte counts of < 200/mm3. At least one fungal organism
      demonstrating in vitro resistance to fluconazole (minimum inhibitory
      concentration, > or = 8 micrograms/mL) was isolated from 26 (41%) of 64 patients
      for whom cultures were positive. When fluconazole-resistant C. albicans was
      isolated, in vitro resistance correlated with clinical thrush. None of 10
      patients from whom only non-albicans species of Candida were isolated had active
      thrush. The patients from whom fluconazole-resistant Candida albicans was
      isolated had lower CD4 cell counts (median, 9/mm3), a greater number of treated
      episodes of thrush (median, 4.5), and a greater median duration of prior
      fluconazole treatment (231 days) than did patients from whom fluconazole
      susceptible C. albicans was isolated (median CD4 cell count, 58/mm3 [P = .004];
      median number of treated episodes of thrush, 2.0 [P = .001]; and median duration
      of prior fluconazole treatment, 10 days [P = .01]; respectively). In a
      multivariate analysis, the number of episodes and duration of fluconazole therapy
      were independent predictors of resistance.

PMID- 8994753
TI  - Retrospective detection of laboratory cross-contamination of Mycobacterium
      tuberculosis cultures with use of DNA fingerprint analysis.
AB  - In 1992-1993, we investigated possible cross-contamination of Mycobacterium
      tuberculosis cultures as part of a study of tuberculosis in Arkansas by using DNA
      fingerprint analysis. Of patients whose isolates were matched, those for whom
      smears were negative and only one culture was positive were identified from
      laboratory records. Clinical, laboratory, DNA fingerprint, and epidemiological
      data were reviewed. Of 259 patients, nine (3.5%) were judged to be due to cross
      contamination. None of these patients had a clinical course consistent with
      tuberculosis. All nine specimens were processed with another isolate with a
      matching DNA fingerprint, and epidemiological connections were not identified
      among any of the patients. To avoid erroneous diagnoses and unnecessary therapy
      and public health investigations, specimens from patients with tuberculosis whose
      smears are negative and only one culture is positive should be investigated for
      cross-contamination. An inconsistent clinical course and a DNA fingerprint that
      matches those of other culture-positive specimens processed concurrently, coupled
      with the lack of an epidemiological connection, suggest cross-contamination.

PMID- 8994754
TI  - Cefepime/amikacin versus ceftazidime/amikacin as empirical therapy for febrile
      episodes in neutropenic patients: a comparative study. The French Cefepime Study
      Group.
AB  - We conducted a randomized multicenter study to compare the efficacy and safety of
      two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g
      t.i.d.] plus amikacin) as first-line therapy for fever in patients with
      hematologic malignancies and neutropenia. A total of 353 patients were randomized
      according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in
      the cefepime group and 107 in the ceftazidime group (90% of all patients) were
      evaluable for efficacy. The polymorphonuclear neutrophil count was < 100/mm3 on
      enrollment for 70% of the patients. The mean duration of neutropenia was 26 days.
      The efficacy in both study arms was comparable, although a trend in favor of
      cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for
      the ceftazidime group). The overall response rate after glycopeptides were added
      to the regimens was 60% for the cefepime group and 51% for the ceftazidime group;
      the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of
      new bacterial infections were 14% vs. 18%, respectively. We conclude that the
      combination cefepime/amikacin is at least as effective as the reference regimen
      of ceftazidime/amikacin in this setting.

PMID- 8994755
TI  - Severe cytomegalovirus infection in immunocompetent patients.
AB  - Severe cytomegalovirus (CMV) infection is rare in previously healthy
      immunocompetent individuals; to our knowledge, only thirty-four such cases have
      been reported in the worldwide literature. Multiorgan involvement was associated
      with a high mortality rate among these patients. Disease that clinically involves
      only the liver or lungs could be fatal; in contrast, none of the patients with
      isolated central nervous system infection died. Although few patients were
      treated with specific antiviral therapy, five of six patients with severe
      infection recovered after receiving therapy with ganciclovir or foscarnet. The
      rarity of severe CMV disease in immunocompetent patients probably precludes the
      performance of a clinical trial to evaluate the efficacy of specific antiviral
      therapy. However, the historically poor prognosis in the absence of such therapy
      suggests that rapid diagnosis of CMV disease and early instigation of specific
      treatment may be important.

PMID- 8994756
TI  - Cost-effectiveness of ampicillin/sulbactam versus imipenem/cilastatin in the
      treatment of limb-threatening foot infections in diabetic patients.
AB  - A cost-effectiveness analysis was performed following a double-blind, randomized
      study of ampicillin/sulbactam (A/S) versus imipenem/cilastatin (I/C) for the
      treatment of limb-threatening foot infections in 90 diabetic patients. There were
      no significant differences between the treatments in terms of clinical success
      rate, adverse-event frequency, duration of study antibiotic treatment, or length
      of hospitalization. Costs of the study antibiotics, treatment of failures and
      adverse events, and hospitalization were calculated. Mean per-patient treatment
      cost in the A/S group was $14,084, compared with $17,008 in the I/C group (P =
      .05), primarily because of lower drug and hospitalization costs and less-severe
      adverse events in the A/S group. Sensitivity analyses varying drug prices or
      hospital costs demonstrated that A/S was consistently more cost-effective than
      I/C. Varying the clinical success rate for each drug revealed that I/C would have
      to be 30% more effective than A/S to change the economic decisions.

PMID- 8994757
TI  - Clostridial endocarditis following penetrating cardiac trauma.

PMID- 8994759
TI  - Emergence of increased resistance to quinupristin/dalfopristin during therapy for
      Enterococcus faecium bacteremia.

PMID- 8994758
TI  - Intramedullary abscess of the spinal cord in a patient with a right-to-left
      shunt: case report.

PMID- 8994760
TI  - Superinfection with Enterococcus faecalis during quinupristin/dalfopristin
      therapy.

PMID- 8994761
TI  - Clarithromycin-associated digoxin toxicity in the elderly.

PMID- 8994762
TI  - Streptococcus anginosus spondylodiskitis.

PMID- 8994763
TI  - Strongyloides stercoralis infection in patients infected with human
      immunodeficiency virus.

PMID- 8994764
TI  - Ciprofloxacin was the culprit--not itraconazole.

PMID- 8994765
TI  - Redefining AIDS: towards a modification of the current AIDS case definition.
AB  - AIDS is defined by the occurrence of an opportunistic infection or tumor
      considered indicative of advanced infection with human immunodeficiency virus
      (HIV). Even though recent modifications have improved the widely used AIDS case
      definition issued by the World Health Organization and the Centers for Disease
      Control and Prevention, the modified version has fallen short of generating a
      globally functional instrument for the surveillance of HIV-related infections.
      The clinical AIDS case definition should be as comprehensive as possible. In many
      countries, only the diagnosis of an AIDS-defining illness will grant the affected
      patient social benefits or access to medical care. An expanded AIDS case
      definition is also likely to improve surveillance of HIV-associated morbidity and
      mortality; increase the awareness of emerging infections; increase the number of
      clinical endpoints in clinical trials; and facilitate the introduction of
      diagnostic tests, screening programs, and preventive measures. Examples of
      opportunistic infections and tumors that could be considered in future
      modifications of the AIDS case definition are discussed in detail.

PMID- 8994766
TI  - Azithromycin-related ototoxicity in patients infected with human immunodeficiency
      virus.

PMID- 8994767
TI  - Cat-scratch disease mimicking pancreatic malignancy: case report.

PMID- 8994768
TI  - Enhanced amphotericin B nephrotoxicity in intensive care patients with elevated
      levels of low-density lipoprotein cholesterol.

PMID- 8994770
TI  - Spontaneous bacterial peritonitis caused by Citrobacter diversus: case report.

PMID- 8994769
TI  - Severe knee arthritis due to Eikenella corrodens following a human bite.

PMID- 8994771
TI  - One-dose treatment with pefloxacin for infection due to multidrug-resistant
      Shigella dysenteriae type 1 in Burundi.

PMID- 8994773
TI  - Primary hydatidosis of the peripheral muscles: treatment with albendazole.

PMID- 8994772
TI  - Testicular abscess due to Streptococcus pneumoniae in an infant with human
      immunodeficiency virus infection.

PMID- 8994774
TI  - Variability of plasma fluconazole levels in patients with hematologic malignancy.

PMID- 8994775
TI  - The global epidemic nature of antimicrobial resistance and the need to monitor
      and manage it locally.
AB  - An antimicrobial agent may be used for years before a gene expressing resistance
      to it emerges in a strain of bacteria somewhere. Progeny of that strain, or of
      others to which the gene is transferred, may then disseminate preferentially
      through global networks of bacterial populations on people or animals treated
      with that agent or with other agents as the gene becomes linked to genes
      expressing resistance to them. Over 100 resistance genes-varying in their
      frequency of emergence, vectors, linkages, and pathways-have thus emerged,
      reemerged, converged, and disseminated irregularly through the world's bacterial
      ecosystems over the last 60 years to reach infecting strains and block treatment
      of infection. We may delay emergence by using agents less and retard
      dissemination by good hygiene, infection control measures, and avoidance of
      agents that select for resistance genes in contiguous populations. Local
      monitoring and management of resistance appear essential because of the
      intricacies of tracing and targeting the problems at each place and because
      national or global surveillance and strategy develop from local information and
      understanding.

PMID- 8994776
TI  - The population genetics of antibiotic resistance.
AB  - Mathematical models are used to ascertain the relationship between the incidence
      of antibiotic treatment and the frequency of resistant bacteria in the commensal
      flora of human hosts, as well as the rates at which these frequencies would
      decline following a cessation of antibiotic use. Recent studies of the population
      biology of plasmid-encoded and chromosomal antibiotic resistance are reviewed for
      estimates of the parameters of these models and to evaluate other factors
      contributing to the fate of antibiotic-resistant bacteria in human hosts. The
      implications of these theoretical and empirical results to the future of
      antibacterial chemotherapy are discussed.

PMID- 8994777
TI  - Consequences of bacterial resistance to antibiotics in medical practice.

PMID- 8994778
TI  - Evolution and dissemination of beta-lactamases accelerated by generations of beta
      lactam antibiotics.
AB  - beta-Lactamases are the principal mechanism of bacterial resistance to beta
      lactam antibiotics. In recent years the number and variety of new beta-lactamases
      detected has risen at an alarming rate, apparently in response to the clinical
      use of novel classes of beta-lactam antibiotics. This paper reviews the structure
      and evolution of beta-lactamases in an attempt to understand the pressures that
      have contributed to their emergence.

PMID- 8994779
TI  - The most frequent aminoglycoside resistance mechanisms--changes with time and
      geographic area: a reflection of aminoglycoside usage patterns? Aminoglycoside
      Resistance Study Groups.
AB  - The aminoglycoside resistance mechanisms revealed by two surveys in Europe and
      other countries have been compared to those revealed in earlier studies.
      Mechanisms have become more complex in all bacterial groups. In Providencia,
      Serratia, Pseudomonas, Acinetobacter, and Staphylococcus species isolates, genus
      specific mechanisms were very common, and it was not possible to see differences
      between different geographic areas. In other Enterobacteriaceae, the increasing
      complexity of mechanisms was most often caused by combinations of gentamicin
      modifying enzymes with AAC(6')-I, which acetylates amikacin but not gentamicin.
      The occurrence of these combinations varied by geographical region and among
      hospitals. The frequency of these combinations correlated with aminoglycoside
      usage in either the geographical regions or in individual hospitals. These broad
      spectrum combinations occurred most frequently in Citrobacter, Enterobacter, and
      Klebsiella species but also occurred in Escherichia, Morganella, Proteus,
      Salmonella, and Shigella species. Often the only clinically available
      aminoglycoside that retained its normal activity was isepamicin.

PMID- 8994780
TI  - Increases in rates of resistance to trimethoprim.
AB  - Trimethoprim alone or in combination with a sulfonamide is an effective and
      relatively inexpensive antibacterial medication. However, a dramatic increase in
      the rate of resistance to trimethoprim along with high-level resistance to
      sulfonamides has been seen during the past two decades. The mechanisms of
      resistance show a remarkable evolutionary adaptation.

PMID- 8994782
TI  - The progressive intercontinental spread of methicillin-resistant Staphylococcus
      aureus.
AB  - Methicillin-resistant Staphylococcus aureus was initially detected in Europe in
      the 1960s, soon after the introduction of methicillin. Naturally-resistant
      strains were isolated in some countries before the use of methicillin or related
      agents. These strains probably spread initially from one or more ancestral
      genetic clones in natural populations of S. aureus by horizontal transfer and
      recombination. These original strains, possibly emerging in many countries, then
      increased in numbers and diversity in hospitals as a result of selection by
      exposure to antibiotics and by cross-infection. After a decline in the 1970s, new
      epidemic strains that differed from the original MRSAs emerged in Australia, the
      United States, and the Irish Republic and have now reached global proportions.
      Most strains are highly resistant to antibiotics and some are only sensitive to
      vancomycin or teicoplanin. Intercountry and intercontinental spread has also
      occurred by transfer of infected or colonized patients or staff. However, the
      main mode of spread is person-to-person within a unit or hospital and
      subsequently to other hospitals in the same country. New epidemic strains have
      continued to emerge and decline for unknown reasons. On the basis of evidence
      from countries where MRSA is not a problem, it has been suggested that early
      detection, effective infection control measures, and rational antibiotic use will
      limit the transmission of these organisms; however, spread is still increasing in
      many countries.

PMID- 8994781
TI  - Trends in bacterial resistance to fluoroquinolones.
AB  - The emergence of resistance to fluoroquinolones in virtually all species of
      bacteria was recognized soon after the introduction of these compounds for
      clinical use more than 10 years ago. Various resistance mechanisms, often
      interdependent, may explain different levels of resistance. Epidemiological
      factors, local antibiotic policies, patients' characteristics, origin of the
      strains, and geographic location are among the factors contributing to highly
      variable resistance rates. During the last several years, resistance to
      fluoroquinolones has remained very high among methicillin-resistant
      Staphylococcus aureus strains and in intensive care unit patients, and it has
      increased among nosocomial isolates of Klebsiella pneumoniae, Serratia
      marcescens, and Pseudomonas aeruginosa. More worrisome are recent reports of an
      overall increase in resistance to fluoroquinolones among bacteria responsible for
      community-acquired infections, such as Escherichia coli, Salmonella species,
      Campylobacter species and Neisseria gonorrhoeae.

PMID- 8994783
TI  - Enterococci acquire new kinds of resistance.
AB  - In recent years, enterococci have become increasingly resistant to a broad range
      of antimicrobial agents. The development of high-level resistance to
      aminoglycosides, penicillins, and glycopeptides singly and in combination has
      important clinical implications. Strains of Enterococcus faecium that are
      resistant to every useful available antibiotic have been described. Resistance to
      penicillin can be due to overproduction of penicillin-binding protein (which has
      low affinity for penicillins) or to production of beta-lactamase. High-level
      resistance of enterococci to gentamicin is due to the synthesis of a modifying
      enzyme. In this case, the synergistic activity of the combination of penicillin
      with any aminoglycoside (except for streptomycin) is totally abolished. Acquired
      resistance to glycopeptides is often plasmid-mediated and is associated with a
      major epidemic potential since certain plasmids are self-transferable from E.
      faecium to a variety of gram-positive organisms, including Staphylococcus aureus.

PMID- 8994784
TI  - Antibiotic resistance in Streptococcus pneumoniae.
AB  - Pneumococci were once among the most highly penicillin-susceptible bacteria.
      However, reports of multidrug-resistant strains have been published since the
      late 1970s. The rapid spread of resistant clones and the emergence of new
      variants of resistance mechanisms call for effective surveillance systems and
      collaboration among clinicians, scientists, the pharmaceutical industry, and
      regulatory and public health agencies.

PMID- 8994785
TI  - Recent evaluation of antimicrobial resistance in beta-hemolytic streptococci.
AB  - Although antimicrobial resistance among bacteria continues to increase and to be
      a clinical problem, the beta-hemolytic streptococci have remained remarkably
      susceptible to most antibiotics. For example, there has not been a single
      documented instance of a clinical isolate of a penicillin-resistant group A
      streptococcus. Moreover, available data indicate that the minimal inhibitory
      concentrations (MICs) of penicillin for group A streptococci have not changed
      during the past 4, decades. In one study, the MIC90 for more than 300 strains of
      group A streptococci was only 0.012 microgram/mL. Resistance to the macrolide
      antibiotics, the tetracyclines, and the sulfa drugs remains more clinically
      important. Outbreaks of macrolide resistance have been documented in several
      parts of the world, but macrolide resistance in most countries of the world
      remains at < 5% among group A streptococci. Despite the fact that clinically
      significant antibiotic resistance has not emerged, careful surveillance is
      required.

PMID- 8994786
TI  - Antimicrobial resistance in Neisseria gonorrhoeae.
AB  - The changing patterns of antimicrobial resistance in Neisseria gonorrhoeae have
      been reviewed regularly since the introduction of antimicrobial therapy in the
      1930s. At present, ceftriaxone, fluoroquinolones, and spectinomycin have remained
      efficient as single-dose treatment of gonorrhea worldwide. To ensure that limited
      resources can be used in the best possible way, continuous surveillance of
      gonococcal resistance to antimicrobials is needed.

PMID- 8994787
TI  - Antibiotic resistance in Neisseria meningitidis.
AB  - Penicillin has long been recognized as the antibiotic of choice for treatment of
      meningococcal infections, but clinicians have recently become concerned about the
      susceptibility of meningococci to penicillin and other antibiotics used in the
      management of meningococcal disease. Strains relatively resistant to penicillin
      (minimum inhibitory concentrations ranging from 0.1 mg/L to 1.28 mg/L) have been
      reported from a large number of countries, although the frequency with which such
      isolates are found varies widely. The mechanism of relative resistance to
      penicillin involves, at least in part, the production of altered forms of one of
      the penicillin-binding proteins. Although treatment with penicillin is still
      effective against these relatively resistant strains, there is evidence that low
      dose treatment regimens can fail. beta-Lactamase production in meningococci is
      extremely rare but has been reported, and this finding is of great concern.
      Resistance to sulfonamides and rifampin is of particular concern in regard to the
      management of contacts of patients with meningococcal disease.

PMID- 8994788
TI  - Antimicrobial resistance in organisms causing diarrheal disease.
AB  - Antimicrobial resistance is becoming increasingly important in the treatment of
      enteric infections, particularly those due to Shigella, Vibrio cholerae,
      enterotoxigenic Escherichia coli (associated with traveler's diarrhea), and
      Salmonella typhi. The rate of antimicrobial resistance is highest in the
      developing world, where the use of antimicrobial drugs is relatively
      unrestricted. Of greatest immediate concern is the need for an effective,
      inexpensive antimicrobial that can be used safely as treatment for small children
      with dysentery due to Shigella, primarily Shigella dysenteriae type 1.

PMID- 8994789
TI  - Multidrug-resistant Salmonella typhi: a worldwide epidemic.
AB  - Since 1989, strains of Salmonella typhi resistant to chloramphenicol, ampicillin,
      and trimethoprim (i.e., multidrug-resistant [MDR] strains) have been responsible
      for numerous outbreaks in countries in the Indian subcontinent, Southeast Asia,
      and Africa. MDR strains have also been isolated with increasing frequency from
      immigrant workers in countries in the Arabian Gulf, as well as in developed
      countries from returning travelers. In all MDR strains so far examined, multiple
      resistance has been encoded by plasmids of the H1 incompatibility group. As a
      result of the widespread dissemination of such strains, chloramphenicol can no
      longer be regarded as the first-line drug for typhoid fever. Because strains are
      also resistant to ampicillin and trimethoprim, the efficacy of these antibiotics
      has also been impaired, and ciprofloxacin is now the drug of choice for typhoid
      fever. Chromosomally encoded resistance to ciprofloxacin has now been observed in
      a small number of strains isolated in the United Kingdom from patients returning
      from the Indian subcontinent, and in at least one case the patient did not
      respond to treatment with this antibiotic. It is regrettable that resistance to
      ciprofloxacin has now emerged in MDR S. typhi, and it is of paramount importance
      to limit the unnecessary use of this vital drug so that its efficacy should not
      be further jeopardized.

PMID- 8994790
TI  - Antimicrobial resistance in anaerobes.
AB  - The development of antibiotic resistance in anaerobic bacteria has a tremendous
      impact on the selection of antimicrobial agents for empirical therapy.
      Susceptibility studies have documented the emergence of antimicrobial resistance
      and indicate distinct differences in resistance patterns related to individual
      hospitals, geographic regions, and antibiotic-prescribing regimens. Resistance to
      beta-lactam drugs, clindamycin, tetracyclines, and 5-nitroimidazoles
      (metronidazole) has been observed. The prime mechanism for resistance to beta
      lactam agents is the production of beta-lactamases. Resistance to clindamycin is
      mediated by modification of the ribosome. Tetracycline resistance is mediated by
      both tetracycline efflux and ribosomal protection. 5-Nitroimidazole resistance
      appears to be caused by a combination of decreased antibiotic uptake and
      decreased nitroreductase activity. The level of chloramphenicol susceptibility
      remains quite high, whereas uniform resistance to aminoglycosides and quinolones
      is observed. Understanding the mechanisms of resistance is critical for both
      informed selection of antimicrobial therapy and the design of new antimicrobial
      agents.

PMID- 8994791
TI  - Drug-resistant tuberculosis: review of the worldwide situation and the WHO/IUATLD
      Global Surveillance Project. International Union Against Tuberculosis and Lung
      Disease.
AB  - The emergence of strains of Mycobacterium tuberculosis that are resistant to
      antimycobacterial agents is a worldwide problem whose global magnitude is not
      well described. We reviewed and tabulated 63 surveys of resistance to
      antituberculous drugs that were performed between 1985 and 1994. Rates of primary
      resistance to isoniazid, administered as a single agent, ranged from 0 to 16.9%
      (median rate, 4.1%); to streptomycin, 0.1%-23.5% (median, 3.5%); to rifampin, 0
      3.0% (median, 0.2%); and to ethambutol, 0-4.2% (median, 0.1%). The rates of
      acquired resistance to these agents, which were higher than those of primary
      resistance, were as follows: isoniazid, 4.0%-53.7% (median rate, 10.6%);
      streptomycin, 0-19.4% (median, 4.9%); rifampin 0-14.5% (median, 2.4%); and
      ethambutol, 0-13.7% (median, 1.8%). The highest rates of multidrug-resistant
      tuberculosis have been reported in Nepal (48.0%), Gujarat, India (33.8%), New
      York City, (30.1%), Bolivia (15.3%), and Korea (14.5%). The WHO (World Health
      Organization) and the IUATLD (International Union Against Tuberculosis and Lung
      Disease) have established a global project of drug resistance surveillance that
      is based on standard epidemiological methods and quality control through an
      extensive network of reference laboratories. Accurate drug resistance
      surveillance data can be used to assess and improve national tuberculosis
      programs.

PMID- 8994792
TI  - Approaches to limiting emergence of antimicrobial resistance in bacteria in human
      populations.
AB  - Infectious diseases continue to be major threats to human health around the
      world. Within the past few years, several divergent groups of organisms have
      emerged as significant causes of morbidity and mortality. Included among these
      are bacteria that are refractory to therapy because of the development of
      resistance to multiple antimicrobial agents. Multidrug resistance in strains of
      Mycobacterium tuberculosis, Streptococcus pneumoniae, Shigella dysenteriae,
      Salmonella typhi, and Enterococcus faecium has been reported. Surveillance of
      resistant microorganisms in the United States and abroad is fragmentary and
      targets relatively few organisms. Surveillance is further hampered by the fact
      that detection of some novel resistance mechanisms is difficult by means of
      current laboratory methods. Both clinicians and public health officials are
      likely to continue to face a variety of challenges regarding surveillance,
      treatment, prevention, and control of drug-resistant infections.

PMID- 8994793
TI  - How to modify conditions limiting resistance in bacteria in animals and other
      reservoirs.
AB  - Antimicrobial agents in veterinary medicine are used for three purposes: therapy,
      prophylaxis, and nutrition. The major public health risk is that selection
      pressure leads to an increase in the pool of resistance genes. Since 1987, the
      nutritional use of antimicrobials in Europe has been regulated by a council
      directive, which demands special investigations into the potential of
      antimicrobials to increase rates of drug resistance. However, the prophylactic
      and therapeutic use of antimicrobials has sometimes led to the emergence of
      resistant bacteria. For example, the selective effect of the prophylactic use of
      gentamicin and the therapeutic use of quinolones led to the emergence of
      resistant salmonellae. To prevent the spread of resistant microorganisms from
      animals to humans, it should be recognized that antibiotics are not suitable as a
      compensation for poor hygiene standards or for the eradication of a pathogen from
      a certain environment. They should be used only by doctors or veterinarians.

PMID- 8994794
TI  - Control of nosocomial antimicrobial-resistant bacteria: a strategic priority for
      hospitals worldwide.
AB  - The rapid emergence and dissemination of antimicrobial-resistant microorganisms
      in hospitals worldwide is a problem of crisis dimensions. The root causes of this
      problem are multifactorial, but the core issues are clear. The emergence of
      antimicrobial resistance is highly correlated with selective pressure that
      results from inappropriate use of antimicrobial agents. Dissemination of
      resistant organisms is facilitated by person-to-person transmission due to
      inconsistent application of basic infection control practices by hospital
      personnel. While control strategies exist, the interventions are not likely to be
      successful unless hospital leaders assume the responsibility for control of
      antimicrobial resistance. Strategic goals for the control of resistant organisms
      should be formulated on the basis of multidisciplinary input from hospital
      personnel. Processes and outcomes relevant to these strategic goals should be
      measured, and the resultant data should be used to design, implement, and
      evaluate systematic measures to increase the appropriate use of antimicrobial
      agents and basic infection control practices. This approach is as relevant to
      hospitals in countries with limited resources as it is to in fully industrialized
      countries.

PMID- 8994795
TI  - Perspectives on chemotherapeutic approaches to antibiotic-resistant bacteria.
AB  - This paper presents an overview of the potential chemotherapeutic approaches to
      antibiotic resistance, what those approaches have achieved, and future avenues of
      exploration. Chemical modifications of existing agent classes, interference with
      resistance mechanisms, searches for inhibitors of novel targets, and alternatives
      to chemotherapy with low-molecular-weight molecules are discussed. The research
      focusing on novel targets and on alternative approaches is most likely to yield
      breakthroughs against problem organisms in the future.

PMID- 8994796
TI  - The role of fundamental research and biotechnology in finding solutions to the
      global problem of antibiotic resistance.
AB  - Resistance to antibiotics is becoming a major problem worldwide. Exacerbating
      this situation is the fact that few new antibiotics are in the development
      pipeline, and, indeed, no novel class of antibiotics has been introduced into
      medical practice in more than 20 years. It is proposed that the solutions to the
      problem of antibiotic resistance will be found only through fundamental research
      that will probably use biotechnology as a tool. A variety of novel approaches
      being utilized in university laboratories and biotechnology companies are
      outlined. Two approaches in particular, namely, Synsorbs and recombinant cationic
      peptide antimicrobials, that have been developed through the Canadian Bacterial
      Diseases Network, a national research consortium, are discussed.

PMID- 8994797
TI  - Antibiotic resistance: a view from the pharmaceutical industry.
AB  - The development of new antibiotics has been successful in significantly reducing
      morbidity and mortality. With increasing use there has occurred an increase in
      antibiotic resistance but not a parallel increase in new agents with
      significantly improved spectrum of activity. Without concerted action from the
      pharmaceutical industry, physicians, academia, health care providers, and
      governments, the prospects look gloomy.

PMID- 8994798
TI  - Strategies for the rational use of antimicrobials.
AB  - The World Health Organization's (WHO) policy on drugs is based on the essential
      drug concept. In order that this policy specifically encompasses antimicrobials,
      several steps must be taken. Adequate information on the management of infectious
      diseases should be readily available to prescribers. Continuing education of
      prescribers, provision of treatment guidelines, and accurate product labeling are
      important as well. Unethical promotion of antimicrobial products by
      pharmaceutical companies should be prohibited. Patterns of drug resistance in
      important pathogens should be monitored. Attempts should be made to monitor drug
      use in terms of both prescription and consumption. Systematic interchange of
      information at the national and international levels within defined networks is
      necessary. The pharmaceutical quality of antimicrobials must be ensured through
      rigorous registration and enforcement procedures. Collaboration between the
      pharmaceutical industry and academics must be ongoing. The WHO is prepared to
      assist countries in developing strategies on the rational use of antimicrobials.

PMID- 8994799
TI  - Surveillance of antimicrobial resistance: the WHONET program.
AB  - Genes expressing resistance to each antimicrobial agent emerged after each agent
      became widely used. More than a hundred such genes now spread selectively through
      global networks of populations of bacteria in humans or animals treated with
      those agents. Information to monitor and manage this spread exists in the
      susceptibility test results of tens of thousands of laboratories around the
      world. The comparability of those results is uncertain, however, and their
      storage in paper files or in computer files with diverse codes and formats has
      made them inaccessible for analysis. The WHONET program puts each laboratory's
      data into a common code and file format at that laboratory, either by serving as
      or by translating from its own computer reporting system. It then enables each
      medical center to analyze its files in ways that help it monitor and manage
      resistance locally and to merge them with files of other centers for
      collaborative national or global surveillance of resistance.

PMID- 8994800
TI  - Reports on surveillance of antimicrobial resistance in individual countries.
AB  - In preparation for the meeting of the World Health Organization Working Group on
      Monitoring and Management of Bacterial Resistance to Antimicrobial Agents,
      representatives of 10 countries were asked to provide brief reports on the status
      of surveillance in their countries. Some gave extensive information on the
      methods used to test susceptibility of nosocomial pathogens to a variety of
      antibiotics; some described in detail the network of reference laboratories
      available to hospitals and individual clinicians for monitoring, identifying, and
      testing infectious agents; others chose to describe how their countries deal with
      the resistance of the most frequently isolated pathogen to a commonly used drug.
      The following summary of these reports shows the broad range of problems
      encountered and solutions undertaken by these 10 countries in dealing with the
      increasingly alarming problem of bacterial resistance to antimicrobial agents.

PMID- 8994801
TI  - Vanadium salts as insulin substitutes: mechanisms of action, a scientific and
      therapeutic tool in diabetes mellitus research.
AB  - Vanadium and its compounds exhibit a wide variety of insulin-like effects. In
      this review, these effects are discussed with respect to the treatment of type I
      and type II diabetes in animal models, in vitro actions, antineoplastic role,
      treatment of IDDM and NIDDM patients, toxicity, and the possible mechanism(s)
      involved. Newly established CytPTK plays a major role in the bioresponses of
      vanadium. It has a molecular weight of approximately 53 kDa and is active in the
      presence of Co2+ rather than Mn2+. Among the protein-tyrosine kinase blockers,
      staurosporine is found to be a potent inhibitor of CytPTK but a poor inhibitor of
      InsRTK. Vanadium inhibits PTPase activity, and this in turn enhances the activity
      of protein tyrosine kinases. Our data show that inhibition of PTPase and protein
      tyrosine kinase activation has a major role in the therapeutic efficacy of
      vanadium in treating diabetes mellitus.

PMID- 8994802
TI  - Chemistry and biology of DNA methyltransferases.
AB  - Recognition of a specific DNA sequence by a protein is probably the best example
      of macromolecular interactions leading to various events. It is a prerequisite to
      understanding the basis of protein-DNA interactions to obtain a better insight
      into fundamental processes such as transcription, replication, repair, and
      recombination. DNA methyltransferases with varying sequence specificities provide
      an excellent model system for understanding the molecular mechanism of specific
      DNA recognition. Sequence comparison of cloned genes, along with mutational
      analyses and recent crystallographic studies, have clearly defined the functions
      of various conserved motifs. These enzymes access their target base in an elegant
      manner by flipping it out of the DNA double helix. The drastic protein-induced
      DNA distortion, first reported for HhaI DNA methyltransferase, appears to be a
      common mechanism employed by various proteins that need to act on bases. A
      remarkable feature of the catalytic mechanism of DNA (cytosine-5)
      methyltransferases is the ability of these enzymes to induce deamination of the
      target cytosine in the absence of S-adenosyl-L-methionine or its analogs. The
      enzyme-catalyzed deamination reaction is postulated to be the major cause of
      mutational hotspots at CpG islands responsible for various human genetic
      disorders. Methylation of adenine residues in Escherichia coli is known to
      regulate various processes such as transcription, replication, repair,
      recombination, transposition, and phage packaging.

PMID- 8994803
TI  - UV-induced cutaneous photobiology.
AB  - Ultraviolet radiation (UVR) present in sunlight is a major environmental factor
      capable of affecting human health and well being. The organ primarily affected by
      UVR is the skin, which is composed of a variety of different cell types. Here,
      UVR is needed for production of active vitamin D as well as producing undesirable
      effects such as sunburn, premature cutaneous photoaging, and promoting skin
      cancer development. Depending on the radiation dose, UVR influences virtually
      every cutaneous cell type investigated differently. Since the end of the
      nineteenth century, sun exposure has been known to induce skin cancer, which is
      now the human malignancy with the most rapidly increasing incidence. In several
      experimental models, mid-range UVR has been demonstrated to be the major cause of
      UV-induced cutaneous tumors. The stratospheric ozone layer protecting the
      terrestrial surface from higher quantum energy solar radiation is being damaged
      by industrial activities resulting in the possibility of increased UVR exposure
      in the future. Investigations in the field of experimental dermatology have shown
      that within the skin an immunosurveillance system exists that may be able to
      detect incipient neoplasms and to elicit a host responses against it. This
      article reviews the literature on studies designed to investigate the effects of
      UVR on cutaneous cellular components, with special focus on the immune system
      within the skin and the development of UV-induced cancer.

PMID- 8994804
TI  - DNA repair functions in heterologous cells.
AB  - Our genetic information is constantly challenged by exposure to endogenous and
      exogenous DNA-damaging agents, by DNA polymerase errors, and thereby inherent
      instability of the DNA molecule itself. The integrity of our genetic information
      is maintained by numerous DNA repair pathways, and the importance of these
      pathways is underscored by their remarkable structural and functional
      conservation across the evolutionary spectrum. Because of the highly conserved
      nature of DNA repair, the enzymes involved in this crucial function are often
      able to function in heterologous cells; as an example, the E. coli Ada DNA repair
      methyltransferase functions efficiently in yeast, in cultured rodent and human
      cells, in transgenic mice, and in ex vivo-modified mouse bone marrow cells. The
      heterologous expression of DNA repair functions has not only been used as a
      powerful cloning strategy, but also for the exploration of the biological and
      biochemical features of numerous enzymes involved in DNA repair pathways. In this
      review we highlight examples where the expression of DNA repair enzymes in
      heterologous cells was used to address fundamental questions about DNA repair
      processes in many different organisms.

PMID- 8994805
TI  - Archaea make it big.

PMID- 8994806
TI  - Holliday bound.

PMID- 8994807
TI  - Protein identification with sequence tags.

PMID- 8994808
TI  - Fibronectin type III domains in yeast detected by a hidden Markov model.

PMID- 8994809
TI  - Zebrafish genetics: mutant cornucopia.
AB  - The initial characterization of mutations from the large-scale mutagenesis of the
      zebrafish genome has been reported. What new insights will we gain about
      vertebrate development from these studies?

PMID- 8994810
TI  - Cell cycle: on target with Myc.
AB  - Recent evidence indicates that the c-Myc proto-oncogene activates transcription
      of cdc25A. The Cdc25A protein phosphatase is required both for progression
      through mitosis and for Myc-induced apoptosis, making cdc25A the most attractive
      Myc target gene identified so far.

PMID- 8994812
TI  - Neuronal firing: does function follow form?
AB  - Neurons generate diverse firing patterns to perform a range of specialized tasks.
      Experiments show that many features of these firing patterns arise from
      distinctive membrane properties, but theoretical work predicts that differences
      in neuronal morphology are also important.

PMID- 8994811
TI  - HIV-1: is Nef a PAK animal?
AB  - HIV-1 Nef is clearly essential for efficient viral replication in vivo, but it
      has been difficult to determine why. Recent evidence that Nef specifically
      activates a PAK-dependent signalling cascade may be the first step in defining
      the mechanism of action of this enigmatic viral protein.

PMID- 8994813
TI  - Cytoskeleton: missing links found?
AB  - The quest for the function of BPAG1, a major hemidesmosomal protein of skin
      keratinocytes, has led to the discovery of a group of protein isoforms derived
      from the same genomic locus that are involved in organizing and integrating
      cytoskeletal networks in sensory neurons.

PMID- 8994814
TI  - Plant transformation: a pilus in Agrobacterium T-DNA transfer.
AB  - Agrobacterium tumefaciens transfers a protein-DNA complex to plant cells in a
      process similar to bacterial conjugation; the mechanism of transfer is beginning
      to be unravelled by biochemical, genetic and electron microscopic studies.

PMID- 8994815
TI  - Cell biology: alternatives to baker's yeast.
AB  - Saccharomyces cerevisiae is an excellent model organism for addressing questions
      in cell biology, but other yeast systems are also providing new insights into
      several fundamental cellular processes.

PMID- 8994816
TI  - Molecular chaperones: clasping the prize.
AB  - The three-dimensional structure of the substrate-binding domain of DnaK, a
      bacterial Hsp70, shows how such molecular chaperones can be so promiscuous in
      recognizing different proteins, yet so accurate in discriminating between
      unfolded and folded forms of their polypeptide substrates.

PMID- 8994817
TI  - Bone growth: coordinating chondrocyte differentiation.
AB  - Two signalling molecules-Indian hedgehog and parathyroid hormone-related peptide
      have been found to function in a negative feedback loop that is crucial for the
      coordinated regulation of the rate and extent of endochondral bone growth.

PMID- 8994819
TI  - Human memory: the hippocampus is the key.
AB  - A recent study of brain-damaged patients with various degrees of amnesia provides
      compelling new evidence that the hippocampus plays a vital role in the laying
      down of new memories. Why existing memories are also affected by hippocampal
      damage is particularly puzzling.

PMID- 8994818
TI  - Chemokines: molecular double agents.
AB  - Chemokines are best known as signalling molecules that attract leukocytes to
      sites of inflammation, but recent results show they are also important regulators
      of hematopoiesis during development.

PMID- 8994820
TI  - Apoptosis: does stress kill?
AB  - A wide variety of cellular stresses can initiate apoptosis, or programmed cell
      death. Recent work shows that the mechanism involves stress-activated protein
      kinase pathways, although the targets of these pathways are unknown at present.

PMID- 8994821
TI  - Plant tropisms: the ins and outs of auxin.
AB  - The Cholodny-Went hypothesis holds that gravitropic curvature of a growing plant
      organ depends on regulated transport of the plant hormone auxin; new studies of
      the agravitropic mutant aux1 of Arabidopsis provide strong evidence in support of
      this hypothesis.

PMID- 8994822
TI  - Mitosis: don't get mad, get even.
AB  - The 'mitotic spindle checkpoint' ensures that, before a cell exits from mitosis,
      all of its chromosomes are aligned on the spindle to form the metaphase plate.
      Mad2 is an essential component of this checkpoint system and it binds
      specifically to unattached kinetochores.

PMID- 8994823
TI  - Vital imaging: two photons are better than one.
AB  - The recently developed technique of two-photon fluorescence microscopy causes
      much less photodamage than conventional confocal microscopy, expanding the
      possibilities for imaging living specimens.

PMID- 8994824
TI  - GFP tagging of budding yeast chromosomes reveals that protein-protein
      interactions can mediate sister chromatid cohesion.
AB  - BACKGROUND: Precise control of sister chromatid separation is essential for the
      accurate transmission of genetic information. Sister chromatids must remain
      linked to each other from the time of DNA replication until the onset of
      chromosome segregation, when the linkage must be promptly dissolved. Recent
      studies suggest that the machinery that is responsible for the destruction of
      mitotic cyclins also degrades proteins that play a role in maintaining sister
      chromatid linkage, and that this machinery is regulated by the spindle-assembly
      checkpoint. Studies on these problems in budding yeast are hampered by the
      inability to resolve its chromosomes by light or electron microscopy. RESULTS: We
      have developed a novel method for visualizing specific DNA sequences in fixed and
      living budding yeast cells. A tandem array of 256 copies of the Lac operator is
      integrated at the desired site in the genome and detected by the binding of a
      green fluorescent protein (GFP)-Lac repressor fusion expressed from the HIS3
      promoter. Using this method, we show that sister chromatid segregation precedes
      the destruction of cyclin B. In mad or bub cells, which lack the spindle-assembly
      checkpoint, sister chromatid separation can occur in the absence of microtubules.
      The expression of a tetramerizing form of the GFP-Lac repressor, which can bind
      Lac operators on two different DNA molecules, can hold sister chromatids together
      under conditions in which they would normally separate. CONCLUSIONS: We conclude
      that sister chromatid separation in budding yeast can occur in the absence of
      microtubule-dependent forces, and that protein complexes that can bind two
      different DNA molecules are capable of holding sister chromatids together.

PMID- 8994825
TI  - Protein phosphatase 2A regulates MPF activity and sister chromatid cohesion in
      budding yeast.
AB  - BACKGROUND: Mitosis is regulated by MPF (maturation promoting factor), the active
      form of Cdc2/28-cyclin B complexes. Increasing levels of cyclin B abundance and
      the loss of inhibitory phosphates from Cdc2/28 drives cells into mitosis, whereas
      cyclin B destruction inactivates MPF and drives cells out of mitosis. Cells with
      defective spindles are arrested in mitosis by the spindle-assembly checkpoint,
      which prevents the destruction of mitotic cyclins and the inactivation of MPF. We
      have investigated the relationship between the spindle-assembly checkpoint,
      cyclin destruction, inhibitory phosphorylation of Cdc2/28, and exit from mitosis.
      RESULTS: The previously characterized budding yeast mad mutants lack the spindle
      assembly checkpoint. Spindle depolymerization does not arrest them in mitosis
      because they cannot stabilize cyclin B. In contrast, a newly isolated mutant in
      the budding yeast CDC55 gene, which encodes a protein phosphatase 2A (PP2A)
      regulatory subunit, shows a different checkpoint defect. In the presence of a
      defective spindle, these cells separate their sister chromatids and leave mitosis
      without inducing cyclin B destruction. Despite the persistence of B-type cyclins,
      cdc55 mutant cells inactivate MPF. Two experiments show that this inactivation is
      due to inhibitory phosphorylation on Cdc28: phosphotyrosine accumulates on Cdc28
      in cdc55 delta cells whose spindles have been depolymerized, and a cdc28 mutant
      that lacks inhibitory phosphorylation sites on Cdc28 allows spindle defects to
      arrest cdc55 mutants in mitosis with active MPF and unseparated sister
      chromatids. CONCLUSIONS: We conclude that perturbations of protein phosphatase
      activity allow MPF to be inactivated by inhibitory phosphorylation instead of by
      cyclin destruction. Under these conditions, sister chromatid separation appears
      to be regulated by MPF activity rather than by protein degradation. We discuss
      the role of PP2A and Cdc28 phosphorylation in cell-cycle control, and the
      possibility that the novel mitotic exit pathway plays a role in adaptation to
      prolonged activation of the spindle-assembly checkpoint.

PMID- 8994826
TI  - Cell cycle-dependent activation of Ras.
AB  - BACKGROUND: Ras proteins play an essential role in the transduction of signals
      from a wide range of cell-surface receptors to the nucleus. These signals may
      promote cellular proliferation or differentiation, depending on the cell
      background. It is well established that Ras plays an important role in the
      transduction of mitogenic signals from activated growth-factor receptors, leading
      to cell-cycle entry. However, important questions remain as to whether Ras
      controls signalling events during cell-cycle progression and, if so, at which
      point in the cell-cycle it is activated. RESULTS: To address these questions we
      have developed a novel, functional assay for the detection of cellular activated
      Ras. Using this assay, we found that Ras was activated in HeLa cells, following
      release from mitosis, and in NIH 3T3 fibroblasts, following serum-stimulated cell
      cycle entry. In each case, peak Ras activation occurred in mid-G1 phase. Ras
      activation in HeLa cells at mid-G1 phase was dependent on RNA and protein
      synthesis and was not associated with tyrosine phosphorylation of Shc proteins
      and their binding to Grb2. Significantly, activation of Ras and the extracellular
      signal regulated (ERK) sub-group of mitogen-activated protein kinases were not
      temporally correlated during G1-phase progression. CONCLUSIONS: Activation of Ras
      during mid-G1 phase appears to differ in many respects from its rapid activation
      by growth factors, suggesting a novel mechanism of regulation that may be
      intrinsic to cell-cycle progression. Furthermore, the temporal dissociation
      between Ras and ERK activation suggests that Ras targets alternate effector
      pathways during G1-phase progression.

PMID- 8994827
TI  - Faciogenital dysplasia protein (FGD1) and Vav, two related proteins required for
      normal embryonic development, are upstream regulators of Rho GTPases.
AB  - BACKGROUND: Dbl, a guanine nucleotide exchange factor (GEF) for members of the
      Rho family of small GTPases, is the prototype of a family of 15 related proteins.
      The majority of proteins that contain a DH (Dbl homology) domain were isolated as
      oncogenes in transfection assays, but two members of the DH family, FGD1 (the
      product of the faciogenital dysplasia or Aarskog-Scott syndrome locus) and Vav,
      have been shown to be essential for normal embryonic development. Mutations to
      the FGD1 gene result in a human developmental disorder affecting specific
      skeletal structures, including elements of the face, cervical vertebrae and
      distal extremities. Homozygous Vav-/- knockout mice embryos are not viable past
      the blastocyst stage, indicating an essential role of Vav in embryonic
      implantation. RESULTS: Here, we show that the microinjection of FGD1 and Vav into
      Swiss 3T3 fibroblasts induces the polymerization of actin and the assembly of
      clustered integrin complexes. FGD1 activates Cdc42, whereas Vav activates Rho,
      Rac and Cdc42. In addition, FGD1 and Vav stimulate the mitogen activated protein
      kinase cascade that leads to activation of the c-Jun kinase SAPK/JNK1.
      CONCLUSIONS: We conclude that FGD1 and Vav are regulators of the Rho GTPase
      family. Along with their target proteins Cdc42, Rac and Rho, FGD1 and Vav control
      essential signals required during embryonic development.

PMID- 8994828
TI  - ELAV, a Drosophila neuron-specific protein, mediates the generation of an
      alternatively spliced neural protein isoform.
AB  - BACKGROUND: Tissue-specific alternative pre-mRNA splicing is a widely used
      mechanism for gene regulation and the generation of different protein isoforms,
      but relatively little is known about the factors and mechanisms that mediate this
      process. Tissue-specific RNA-binding proteins could mediate alternative pre-mRNA
      splicing. In Drosophila melanogaster, the RNA-binding protein encoded by the elav
      (embryonic lethal abnormal visual system) gene is a candidate for such a role.
      The ELAV protein is expressed exclusively in neurons, and is important for the
      formation and maintenance of the nervous system. RESULTS: In this study,
      photoreceptor neurons genetically depleted of ELAV, and elav-null central nervous
      system neurons, were analyzed immunocytochemically for the expression of neural
      proteins. In both situations, the lack of ELAV corresponded with a decrease in
      the immunohistochemical signal of the neural-specific isoform of Neuroglian,
      which is generated by alternative splicing. Furthermore, when ELAV was expressed
      ectopically in cells that normally express only the non-neural isoform of
      Neuroglian, we observed the generation of the neural isoform of Neuroglian.
      CONCLUSIONS: Drosophila ELAV promotes the generation of the neuron-specific
      isoform of Neuroglian by the regulation of pre-mRNA splicing. The findings
      reported in this paper demonstrate that ELAV is necessary, and the ectopic
      expression of ELAV in imaginal disc cells is sufficient, to mediate neuron
      specific alternative splicing.

PMID- 8994829
TI  - Change in plasma membrane Ca2(+)-ATPase splice-variant expression in response to
      a rise in intracellular Ca2+.
AB  - BACKGROUND: Most eukaryotic genes are divided into introns and exons. Upon
      transcription, the intronic segments are eliminated and the exonic sequences
      spliced together through a series of complex processing events. Alternative
      splicing refers to the optional inclusion or exclusion of specific exons in
      transcripts derived from a single gene, which leads to structural and functional
      changes in the encoded proteins. Although many components of the machinery
      directing the physical excision of introns and joining of exons have been
      elucidated in recent years, the signaling pathways regulating the activity of the
      machinery remain largely unexplored. RESULTS: A calcium-mediated signaling
      pathway regulates alternative splicing at a specific site of human plasma
      membrane calcium pump-2 transcripts. This site consists of three exons, which are
      differentially used in a tissue-specific manner. In IMR32 neuroblastoma cells, a
      transient elevation of intracellular calcium changed the predominant pattern from
      one in which all three exons are included to the coexpression of a variant
      including only the third exon. Western-blot analysis demonstrated that the newly
      expressed mRNAs are faithfully translated. Once induced, the new splicing pattern
      was maintained over multiple cell divisions. Protein synthesis was not required
      to induce the alternative splice change, indicating that all components necessary
      for a rapid cellular response are present in the cells. CONCLUSIONS: Calcium
      signaling exerts a direct influence on the regulation of alternative splicing.
      Notably, a calcium-mediated change in the expression of alternatively spliced
      variants of a calcium regulatory protein was discovered. The change in splicing
      occurs quickly, is persistent but reversible and leads to a corresponding change
      in protein expression. The specific nature in which differently spliced protein
      variants are expressed, and now the fact that their expression can be regulated
      by distinct intracellular signaling pathways, suggests that the regulation of
      alternative splicing by physiological stimuli is a widespread regulatory
      mechanism by which a cell may coordinate its responses to environmental cues.

PMID- 8994830
TI  - Mutations that suppress the thermosensitivity of green fluorescent protein.
AB  - BACKGROUND: The green fluorescent protein (GFP) of the jellyfish Aequorea
      victoria has recently attracted great interest as the first example of a cloned
      reporter protein that is intrinsically fluorescent. Although successful in some
      organisms, heterologous expression of GFP has not always been straight forward.
      In particular, expression of GFP in cells that require incubation temperatures
      around 37 degrees C has been problematic. RESULTS: We have carried out a screen
      for mutant forms of GFP that fluoresce more intensely than the wild-type protein
      when expressed in E. coli at 37 degrees C. We have characterized a bright mutant
      (GFPA) with reduced sensitivity to temperature in both bacteria and yeast, and
      have shown that the amino acids substituted in GFPA act by preventing temperature
      dependent misfolding of the GFP apoprotein. We have shown that the excitation and
      emission spectra of GFPA can be manipulated by site-directed mutagenesis without
      disturbing its improved folding characteristics, and have produced a thermostable
      folding mutant (GFP5) that can be efficiently excited using either long
      wavelength ultraviolet or blue light. Expression of GFP5 results in greatly
      improved levels of fluorescence in both microbial and mammalian cells cultured at
      37 degrees C. CONCLUSIONS: The thermotolerant mutants of GFP greatly improve the
      sensitivity of the protein as a visible reporter molecule in bacterial, yeast and
      mammalian cells. The fluorescence spectra of these mutants can be manipulated by
      further mutagenesis without deleteriously affecting their improved folding
      characteristics, so it may be possible to engineer a range of spectral variants
      with improved tolerance to temperature. Such a range of sensitive reporter
      proteins will greatly improve the prospects for GFP-based applications in cells
      that require relatively high incubation temperatures.

PMID- 8994831
TI  - Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless
      signalling in intact cells.
AB  - BACKGROUND: Exposing eukaryotic cells to lithium ions (Li+) during development
      has marked effects on cell fate and organization. The phenotypic consequences of
      Li+ treatment on Xenopus embryos and sporulating Dictyostelium are similar to the
      effects of inhibition or disruption, respectively, of a highly conserved protein
      serine/threonine kinase, glycogen synthase kinase-3 (GSK-3). In Drosophila, the
      GSK-3 homologue is encoded by zw3sgg, a segment-polarity gene involved in
      embryogenesis that acts downstream of wg. In higher eukaryotes, GSK-3 has been
      implicated in signal transduction pathways downstream of phosphoinositide 3
      kinase and mitogen-activated protein kinases. RESULTS: We investigated the effect
      of Li+ on the activity of the GSK-3 family. At physiological doses, Li+ inhibits
      the activity of human GSK-3 beta and Drosophila Zw3Sgg, but has no effect on
      other protein kinases. The effect of Li+ on GSK-3 is reversible in vitro.
      Treatment of cells with Li+ inhibits GSK-3-dependent phosphorylation of the
      microtubule-associated protein Tau. Li+ treatment of Drosophila S2 cells and rat
      PC12 cells induces accumulation of cytoplasmic Armadillo/beta-catenin,
      demonstrating that Li+ can mimic Wingless signalling in intact cells, consistent
      with its inhibition of GSK-3. CONCLUSIONS: Li+ acts as a specific inhibitor of
      the GSK-3 family of protein kinases in vitro and in intact cells, and mimics
      Wingless signalling. This reveals a possible molecular mechanism of Li+ action on
      development and differentiation.

PMID- 8994832
TI  - Apo-3, a new member of the tumor necrosis factor receptor family, contains a
      death domain and activates apoptosis and NF-kappa B.
AB  - BACKGROUND: Two receptors that contain the so-called "death domain' have been
      described to date: tumor necrosis factor receptor 1 (TNFR1) and Fas/Apo-1 (CD95);
      both belong to the TNFR gene family. The death domain of TNFR1 mediates the
      activation of programmed cell death (apoptosis) and of the transcription factor
      NF-kappa B, whereas the death domain of CD95 only appears to activate apoptosis.
      RESULTS: We have identified an additional member of the TNFR family, which we
      have named Apo-3. Apo-3 is a transmembrane protein of approximately 47 kDa that
      has similarity of members of the TNFR family in its extracellular, cysteine-rich
      domains. In addition, Apo-3 resembles TNFR1 and CD95 in that it contains a
      cytoplasmic death domain. The Apo-3 gene mapped to human chromosome 1p36.3, and
      Apo-3 mRNA was detected in several human tissues, including spleen, thymus,
      peripheral blood lymphocytes, small intestine and colon. Ectopic expression of
      Apo-3 in HEK293 or HeLa cells induced marked apoptosis. CrmA, a poxvirus
      inhibitor of Ced-3-like proteases which blocks death signaling by TNFR1 and CD95,
      inhibited Apo-3-induced apoptosis. Ectopic expression of Apo-3 also induced the
      activation of NF-kappa B. Apo-3 did not specifically bind to the Apo-2 ligand,
      suggesting the existence of a distinct ligand for Apo-3. CONCLUSIONS: These
      results identify Apo-3 as a third member of the TNFR family that activates
      apoptosis, and suggest that Apo-3, TNFR1 and CD95 engage a common apoptotic cell
      death machinery. Apo-3 resembles TNFR1 because it can stimulate NF-kappa B
      activity and regulate apoptosis. Apo-3 mRNA is expressed in various tissues,
      consistent with the possibility that this receptor may regulate multiple
      signaling functions.

PMID- 8994833
TI  - CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and
      replication of HIV-1.
AB  - BACKGROUND: The negative factor (Nef) of human and simian immunodeficiency
      viruses (HIV-1, HIV-2 and SIV) is required for high levels of viremia and
      progression to AIDS. Additionally, Nef leads to cellular activation, increased
      viral infectivity and decreased expression of CD4 on the cell surface.
      Previously, we and others demonstrated that Nef associates with a cellular serine
      kinase (NAK) activity. Recently, it was demonstrated that NAK bears structural
      and functional similarity to p21-activated kinases (PAKs). RESULTS: In this
      study, we demonstrate that Nef not only binds to but also activates NAK via the
      small GTPases CDC42 and Rac1. First, the dominant-negative PAK (PAKR), via its
      GTPase-binding domain, and dominant-negative GTPases (CDC42Hs-N17 and Rac1-N17)
      block the ability of Nef to associate with and activate NAK. Second,
      constitutively active small GTPases (CDC42Hs-V12 and Rac1-V12) potentiate the
      effects of Nef. Third, interactions between Nef and NAK result in several
      cellular effector functions, such as activation of the serum-response pathway.
      And finally, PAKR, CDC42Hs-N17 and Rac1-N17 decrease levels of HIV-1 production
      to those of virus from which the nef gene is deleted. CONCLUSIONS: By activating
      NAK via small GTPases and their downstream effectors, Nef interacts with
      regulatory pathways required for cell growth, cytoskeletal rearrangement and
      endocytosis. Thus, NAK could participate in the budding of new virions, the
      modification of viral proteins and the increased endocytosis of surface molecules
      such as CD4. Moreover, blocking the activity of these GTPases could lead to new
      therapeutic interventions against AIDS.

PMID- 8994834
TI  - A subset of clones in the chick telencephalon arranged in rostrocaudal arrays.
AB  - BACKGROUND: Different areas of the vertebrate central nervous system appear to
      follow different rules during development for determining the position of sibling
      cells. For example, in the chick hindbrain, clones are frequently confined to a
      single functional unit that derives from a single rhombomere. In contrast, clones
      in the mammalian cerebral cortex often cross functional boundaries because of the
      extensive migration of sibling cells in orthogonal directions. We have
      investigated whether the pattern of clonal distribution in the chick
      telencephalon is similar to that of the hindbrain or to the more functionally
      analogous mammalian cerebral cortex. Progenitor cells in the chick telencephalon
      were marked using a retroviral library encoding alkaline phosphatase and over
      10(5) distinct molecular tags. Patterns of dispersion were detected using
      alkaline phosphatase histochemistry, followed by the recovery and sequencing of
      the molecular tag. We also analyzed the phenotypes of cells that occurred within
      the clones. RESULTS: A subset of progenitors gave rise to clones that were found
      in rostrocaudal arrays resembling tubes. Arrays were restricted in the
      mediolateral and dorsoventral planes but could span up to 4 mm in the
      rostrocaudal direction. They were found throughout the telencephalon and a single
      clone often spanned more than one telencephalic nucleus. Rostrocaudal clones
      comprised 60% of clones containing five or more cells and contained many
      different types of neurons, astrocytes, oligodendrocytes, or various combinations
      of these cell types. CONCLUSIONS: Telencephalic progenitors are multipotent,
      producing progeny that become distinct cell types. Clonally related cells can
      migrate rostrocaudally within domains that are restrained in the mediolateral and
      dorsoventral directions. A subset of rostrocaudal clones resemble those seen in
      the mammalian cerebral cortex, with respect to the crossing of functional
      boundaries, but all rostrocaudal clones differ from the cerebral cortical clones
      in the pattern of spread of sibling cells, with the rostrocaudal clones being
      more constrained in the mediolateral and dorsoventral directions. A role for
      lineage in the patterning of the chick forebrain is supported by these
      observations. In addition, these data suggest a role for cues within the
      telencephalic marginal zone that serve to guide clones in their rostrocaudal
      migration.

PMID- 8994835
TI  - Synergistic interactions between XPC and p53 mutations in double-mutant mice:
      neural tube abnormalities and accelerated UV radiation-induced skin cancer.
AB  - The significance of DNA repair to human health has been well documented by
      studies on xeroderma pigmentosum (XP) patients, who suffer a dramatically
      increased risk of cancer in sun-exposed areas of their skin [1,2]. This autosomal
      recessive disorder has been directly associated with a defect in nucleotide
      excision-repair (NER) [1,2]. Like human XP individuals, mice carrying homozygous
      mutations in XP genes manifest a predisposition to skin carcinogenesis following
      exposure to ultraviolet (UV) radiation [3-5]. Recent studies have suggested that,
      in addition to roles in apoptosis [6] and cell-cycle checkpoint control [7] in
      response to DNA damage, p53 protein may modulate NER [8]. Mutations in the p53
      gene have been observed in 50% of all human tumors [9] and have been implicated
      in both the early [10] and late [11] stages of skin cancer. To examine the
      consequences of a combined deficiency of the XPC and the p53 proteins in mice, we
      generated double-mutant animals. We document a spectrum of neural tube defects in
      XPC p53 mutant embryos. Additionally, we show that, following exposure to UV-B
      radiation, XPC p53 mutant mice have more severe solar keratosis and suffer
      accelerated skin cancer compared with XPC mutant mice that are wild-type with
      respect to p53.

PMID- 8994836
TI  - Selection for beta 2-microglobulin mutation in mismatch repair-defective
      colorectal carcinomas.
AB  - Novel peptide antigens complexed with human leukocyte antigen (HLA) and beta 2
      microglobulin (beta 2M) molecules are presented at the cell surface to cytotoxic
      T lymphocytes (CTLs), provoking lysis of the antigen-presenting cell [1]. In
      tumor cells, genetically altered or abnormally expressed proteins provide a
      source of peptides that can be presented to CTLs; the resulting anti-tumour CTL
      responses may provide part of the body's defence against cancer. Disabling
      mutations in the HLA and beta 2M proteins required for peptide presentation allow
      a tumour cell to escape destruction by CTLs. Cells with deficient DNA mismatch
      repair have high spontaneous mutation rates [2] and produce many altered proteins
      that are a potential source of numerous unique peptides. Mutator tumour cells
      might therefore be particularly vulnerable to immune surveillance and CTL attack.
      Mutator phenotypes [3,4] and loss of beta 2M (or HLA) expression [5,6] are both
      relatively common among sporadic colorectal tumours. We have compared the
      frequency of beta 2M mutations in sporadic colorectal and other tumours with and
      without a mutator phenotype. Mutations were more frequent among colorectal
      tumours with the microsatellite instability indicative of a defect in DNA
      mismatch repair. The inactivating beta 2M mutations were predominantly
      frameshifts, which is consistent with the underlying mismatch repair defects.
      Evasion of immune surveillance by acquiring beta 2M mutations therefore occurs at
      high frequency in tumour cells with a mutator phenotype due to defective DNA
      mismatch repair.

PMID- 8994837
TI  - Biodiversity, genomes, and DNA sequence databases.
AB  - There are approximately 1.4 million organisms on this planet that have been
      described morphologically but there is no comparable coverage of biodiversity at
      the molecular level. Little more than 1% of the known species have been subject
      to any molecular scrutiny and eukaryotic genome projects have focused on a group
      of closely related model organisms. The past year, however, has seen an
      approximately 80% increase in the number of species represented in sequence
      databases and the completion of the sequencing of three prokaryotic genomes.
      Large-scale sequencing projects seem set to begin coverage of a wider range of
      the eukaryotic diversity, including green plants, microsporidians and
      diplomonads.

PMID- 8994838
TI  - Gene structure and organization in Caenorhabditis elegans.
AB  - The sequencing of the 100 Mb Caenorhabditis elegans genome-containing
      approximately 14,000 genes-is approximately 50% complete. One of its most
      interesting features is its compactness; introns and intergenic distances are
      unusually small and, surprisingly, approximately 25% of genes are contained in
      polycistronic transcription units (operons) with only approximately 100 bp
      between genes.

PMID- 8994839
TI  - Genome research and evolution in trypanosomes.
AB  - Trypanosoma brucei and Trypanosoma cruzi cause different human diseases. As
      strategies for immune evasion, T. brucei undergone antigenic variation whereas T.
      cruzi becomes an intracellular organism. This fundamental difference is reflected
      by major differences in their genome organizations. Recent comparisons of their
      gene sequences indicate that these two trypanosome species are highly divergent
      evolutionarily.

PMID- 8994840
TI  - Unravelling the Leishmania genome.
AB  - The past few years have been significant advances in our understanding of
      eukaryotic genomes. In the field of parasitology, this is best exemplified by the
      application of genome mapping techniques to the study of genome structure and
      function in the protozoan parasite, Leishmania. Although much is known about the
      organism and the diseases it causes, molecular genetics has only recently begun
      to play a major part in elucidating some of the unusual characteristics of this
      interesting parasite. Mapping of the small (35 Mb) genome and determination of
      the functional role of genes by the application of in vitro homologous gene
      targeting techniques are revealing novel avenues for the development of
      prophylactic measures.

PMID- 8994841
TI  - Cereal genome analysis using rice as a model.
AB  - Researchers are eagerly waiting for the physical map of rice to become completed
      and available for use as a model for all cereals. The most significant advances
      of the past year have been the progress toward positional cloning of genes and
      the identification of quantitative trait loci (QTL) from detailed restriction
      fragment length polymorphism maps. Future focus will be: first, the enhanced
      dissemination and integration of the available data in World Wide Web accessible
      databases for easy comparison of genetic and physical mapping data across various
      species; second, the expanded distribution of a wide variety of DNA materials
      (cDNA clones, yeast artificial chromosomes, bacterial artificial chromosomes and
      other probes) for use in other cereals on the basis of the rice model map; and
      third, the applied breeding by locating and isolating sequences corresponding to
      important agronomic traits, often correlating with QTL.

PMID- 8994842
TI  - Gen(om)e duplications in the evolution of early vertebrates.
AB  - Phylogenetic analyses and sequence surveys of developmental regulator gene
      families indicate that two large-scale gene duplications, most likely genome
      duplications, occurred in ancestors of vertebrates. Relaxed constraints allowed
      duplicated and thus redundant genes to diverge in a two stage mechanism. Neutral
      changes dominated at first but then positively selected regulatory changes
      evolved the novel and increasingly complex vertebrate developmental program.

PMID- 8994843
TI  - Comparative maps: adding pieces to the mammalian jigsaw puzzle.
AB  - Comparative maps display the chromosomal location of homologous genes in
      different species and highlight genetic segments that are conserved in evolution.
      These maps are used to study chromosomal changes that occurred during the
      divergence of mammalian lineages, to identify candidates for hereditary disease
      genes, and to facilitate mapping in other species. Recently, physical mapping in
      regions of known conserved linkage has revealed previously undetected chromosomal
      changes that may provide clues to understanding chromosomal structure and
      function and evolutionary processes. The availability of these data in
      electronically accessible formats is critical to the growth and analysis of
      comparative maps.

PMID- 8994844
TI  - Human evolution and the mitochondrial genome.
AB  - The use of mitochondrial DNA (mtDNA) continues to dominate studies of human
      genetic variation and evolution. Recent work has re-affirmed the strict maternal
      inheritance of mtDNA, yielded new insights into the extent and nature of intra
      individual variation, supported a recent African origin of human mtDNA, and amply
      demonstrated the utility of mtDNA in tracing population history and in analyses
      of ancient remains.

PMID- 8994845
TI  - Human evolution and the Y chromosome.
AB  - The past two years have seen the increased study of Y-chromosome polymorphisms
      and their relationship to human evolution and variation. Low Y-chromosome
      sequence diversity indicates that the common ancestor of all extant Y chromosomes
      lived relatively recently and the consensus of estimates of time to the most
      recent common ancestor concur with estimates of the mitochondrial DNA ancestor;
      but we do not know where this 'Adam' lived. Though the reason for low nucleotide
      diversity on the Y-chromosome remains unresolved, some of the mutations are
      proving highly informative in tracing human prehistoric migrations and are
      generating new hypotheses on human colonizations and migrations. The recent
      discovery of highly polymorphic microsatellites on the Y offers new possibilities
      for the investigation of more recent human evolutionary events, including the
      identification of male founders.

PMID- 8994846
TI  - The origin of interspersed repeats in the human genome.
AB  - Over a third of the human genome consists of interspersed repetitive sequences
      which are primarily degenerate copies of transposable elements. In the past year,
      the identities of many of these transposable elements were revealed. The emerging
      concept is that only three mechanisms of amplification are responsible for the
      vast majority of interspersed repeats and that with each autonomous element a
      number of dependent non-autonomous sequences have co-amplified.

PMID- 8994847
TI  - The complexities of viral genome analysis: the primate lentiviruses.
AB  - Analysis of sequence information from RNA-based replication systems continues to
      challenge the computational molecular biology community. Recent sequence data
      from the study of primate lentiviruses indicate that extreme sequence
      heterogeneity, recombination, and cross-species transmissions are all observed in
      HIV evolution. These types of events will continue to make the development of
      effective anti-retroviral therapies difficult.

PMID- 8994848
TI  - Complete genome sequences of cellular life forms: glimpses of theoretical
      evolutionary genomics.
AB  - The availability of complete genome sequences of cellular life forms creates the
      opportunity to explore the functional content of the genomes and evolutionary
      relationships between them at a new qualitative level. With the advent of these
      sequences, the construction of a minimal gene set sufficient for sustaining
      cellular life and reconstruction of the genome of the last common ancestor of
      bacteria, eukaryotes, and archaea become realistic, albeit challenging, research
      projects. A version of the minimal gene set for modern-type cellular life derived
      by comparative analysis of two bacterial genomes, those of Haemophilus influenzae
      and Mycoplasma genitalium, consists of approximately 250 genes. A comparison of
      the protein sequences encoded in these genes with those of the proteins encoded
      in the complete yeast genome suggests that the last common ancestor of all extant
      life might have had an RNA genome.

PMID- 8994850
TI  - Neutral theory of molecular evolution.
AB  - DNA sequence data are generally interpreted as favouring Kimura's neutral theory
      but not without dissent and often with a great deal of controversy with respect
      to molecular clocks, DNA polymorphism, adaptive evolution, and gene genealogy.
      Although the theory serves as a guiding principle, many issues concerning
      mutation, recombination, and selection remain unsettled. Of particular importance
      is the need for more knowledge about the function and structure of molecules.

PMID- 8994849
TI  - Exploiting the complete yeast genome sequence.
AB  - The completion of the genome sequence of the budding yeast Saccharomyces
      cerevisiae marks the dawn of an exciting new era in eukaryotic biology that will
      bring with it a new understanding of yeast, other model organisms, and human
      beings. This body of sequence data benefits yeast researchers by obviating the
      need for piecemeal sequencing of genes, and allows researchers working with other
      organisms to tap into experimental advantages inherent in the yeast system and
      learn from functionally characterized yeast gene products which are their
      proteins of interest. In addition, the yeast post-genome sequence era is serving
      as a testing ground for powerful new technologies, and proven experimental
      approaches are being applied for the first time in a comprehensive fashion on a
      complete eukaryotic gene repertoire.

PMID- 8994851
TI  - Genomes and evolution.

PMID- 8994852
TI  - On hubris and humility.

PMID- 8994853
TI  - Downstream signals initiated in mast cells by Fc epsilon RI and other receptors.
AB  - The significant contributions this past year to our understanding of IgE receptor
      (Fc epsilon RI) signaling in mast cells include studies with truncated Syk in a
      vaccinia expression system and Syk-negative variants of rat basophilic (RBL-2H3)
      cells. These studies demonstrate an essential role for Syk in initiating signals
      for secretion and release of arachidonic acid via phospholipase A2 and mitogen
      activated protein kinase. A newly recognized addition to the repertoire of Fc
      epsilon RI-mediated signaling systems is the activation of sphingosine kinase,
      which contributes to calcium mobilization in mast cells. Advances have been made
      in our understanding of other receptors that regulate proliferation and
      differentiation of mast cells, and in our understanding of the ability of mast
      cells to mount acquired and acute responses to antigenic and bacterial challenge.

PMID- 8994854
TI  - Fc epsilon RI on antigen-presenting cells.
AB  - The high-affinity receptor for IgE, Fc epsilon RI, expressed on antigen
      presenting cells such as monocytes and Langerhans' cells exhibits profound
      differences to its homologue expressed on mast cells and basophils. The lack of
      the beta chain, the presence of an intracellular pool of preformed alpha chains,
      highly variable surface expression, and its function (to provide antigen focusing
      for T cells) are some of the main issues which have led us to consider the
      functional role of this receptor in a new light.

PMID- 8994855
TI  - Histamine-releasing factors.
AB  - There is increasing evidence that human basophils accumulate at sites of chronic
      inflammation, and, in particular, in allergic asthma. Investigators have,
      therefore, become very interested in identifying proteins that activate these
      cells. Recently, the gene encoding a candidate for this function, a novel
      molecule, the IgE-dependent histamine-releasing factor, was cloned.

PMID- 8994856
TI  - Anti-IgE and anti-Fc epsilon RI autoantibodies in clinical allergy.
AB  - Autoantibodies recognizing critical effector molecules of type I allergic
      reactions have been identified. Anti-IgE autoantibodies occur at high frequencies
      not only in atopic diseases but also in healthy individuals and, depending on
      their epitope specificities, may promote or prevent the elicitation of allergic
      symptoms. In contrast, anti-Fc epsilon RI autoantibodies with basophil/mast cell
      activating properties were selectively found in patients with chronic urticaria,
      a condition characterized by the continuous degranulation of mast cells. Thus,
      humoral anti-Fc epsilon RI autoreactivity defines a distinctive subset of chronic
      urticaria and may well be the causative and pathogenetic principle in this
      disease.

PMID- 8994857
TI  - Eosinophils in allergic reactions.
AB  - Mainly located in the skin or mucosa of patients with allergic diseases,
      eosinophils contribute directly to tissue damage and chronic inflammation. The
      past year has seen significant advances in the study of the factors involved in
      the specific tissue recruitment of eosinophils, including chemoattractants and
      their receptors. New data have been obtained on the synthesis by eosinophils of
      various cytokines mostly released by immune complexes.

PMID- 8994858
TI  - Biology and genetics of atopic disease.
AB  - Several immunological disorders including allergic rhinitis, bronchial asthma,
      atopic dermatitis, food allergies, urticaria, nonhereditary angioedema, systemic
      anaphylaxis, and allergic conjunctivitis are associated with a positive family
      history, and share a positive response in the Prausnitz-Kuster (wheal and flare)
      reaction. Studies have shown that 20-30% of the population has a strong genetic
      predisposition for this condition, termed atopy, whose hallmark is a greatly
      elevated serum IgE concentration. A great deal is known about the cellular
      interactions that mediate the sensitization, immediate and late-phase reactions
      that follow encounters with allergen, as well as about the cell surface and
      signaling events that result in mediator release from inflammatory cells. Less is
      known of the genes that confer genetic predisposition for atopy; however, a
      worldwide effort to identify atopy genes is making significant progress.

PMID- 8994859
TI  - Autoimmunity. How to know thy self.

PMID- 8994860
TI  - T cell selection and autoimmunity: flexibility and tuning.
AB  - Peptide-MHC interactions govern the fate of T cells in the thymus and the
      peripheral T cell repertoire. Recent progress has involved investigating how
      different peptides influence T cell selection and mature T cell function and the
      subsequent implications for tolerance and autoimmunity.

PMID- 8994861
TI  - Mechanisms of tolerance to self.
AB  - Several mechanisms exist to prevent lymphocytes from reacting against self
      antigens. As T cells develop in the thymus and express antigen-specific
      receptors, those with high-affinity to self-antigens existing within the thymus
      are deleted. Low-affinity self-reactive T cells and T cells with receptors
      against antigens not represented intrathymically will mature and join the
      peripheral T cell pool. They may either ignore self-antigens expressed by tissues
      unable to activate T cells through a lack of the appropriate costimulator
      signals, or they may, under certain conditions, be deleted or rendered anergic
      and unable to respond. Likewise, B cells that express surface Ig receptors with
      high binding affinity to membrane-bound self-antigens present in the bone marrow
      will be rescued by receptor editing or will be deleted, whereas those of lower
      affinity will migrate to the periphery in either an anergic or indifferent state
      depending on the degree of receptor engagement by antigen. Once there, their
      ultimate fate is determined by the availability of T cell help.

PMID- 8994862
TI  - Costimulation and autoimmunity.
AB  - The past year has seen significant advances in our understanding of the role of
      the B7-CD28/CTLA-4 pathway in T cell activation and self-tolerance. Recent
      studies have demonstrated that CTLA-4 is a critical negative regulator of T cell
      activation and autoreactivity, revealing a previously unsuspected means by which
      costimulation is involved in the maintenance and breakdown of self-tolerance.
      Manipulation of this costimulatory pathway in animal models of autoimmunity has
      shown an important role for this pathway in both the initiation and progression
      of autoimmune diseases.

PMID- 8994863
TI  - Epitope spreading.
AB  - Epitope (determinant) spreading is the development of immune responses to
      endogenous epitopes secondary to the release of self antigens during a chronic
      autoimmune or inflammatory response. The past year has seen considerable advances
      in our understanding of the contribution of epitope spreading to the chronic
      pathogenesis of experimental T-cell-mediated and antibody-mediated autoimmune
      diseases. Most significantly, conclusive functional evidence for a major role for
      epitope spreading in the chronic pathogenesis of murine relapsing-remitting
      experimental autoimmune encephalomyelitis, a CD4+ T-cell-mediated model of
      multiple sclerosis, was forthcoming.

PMID- 8994864
TI  - Manipulation of the Th1/Th2 balance in autoimmune disease.
AB  - Many autoimmune diseases are caused by autopathogenic Th1 cells. Because in vitro
      Th1 and Th2 cells cross-regulate each other, it is likely that the induction of
      self-antigen-specific Th2 cells can prevent autoimmune disease. In the past year,
      investigators have further defined the role of Th1 and Th2 cytokines in the
      induction and regulation of autoimmunity. Furthermore, the role of MHC-antigen-T
      cell avidity (strength of signal) in inducing such protective immune responses
      has been elucidated.

PMID- 8994865
TI  - Genetic basis of systemic lupus erythematosus.
AB  - Recent studies have emphasized that systemic lupus erythematosus is a complex
      genetic trait with contributions from the MHC and multiple non-MHC genes. Genome
      wide linkage studies in murine models of lupus have mapped the positions of a
      number of non-MHC loci, but the contributing genes have not yet been identified.
      Recent studies in human systemic lupus erythematosus have found an association
      with a particular FCGR2A allele. Although susceptibility genes in lupus are
      unlikely to involve mutations with severe functional consequences, murine
      knockout models that develop lupus-like features may provide insight into the
      pathogenetic mechanisms and contributing genes in the human disease.

PMID- 8994866
TI  - B cells in systemic autoimmune disease: recent insights from Fas-deficient mice
      and men.
AB  - In mice functionally deficient for either Fas or Fas ligand expression, the
      failure of Fas-ligand-expressing cytotoxic T cells to eliminate autoreactive B
      cells can result in excessive autoantibody production. Recent in vitro studies
      have shown that B cells activated by CD40 ligand become extremely sensitive to
      Fas-mediated apoptosis while IL-4 and/or surface IgM receptor engagement protects
      B cells from Fas ligand cytolysis. Potential in vivo sites for Fas ligand
      regulation of self-reactive B cells have been suggested and implications for
      human disease have been investigated.

PMID- 8994867
TI  - The immune response to islets in experimental diabetes and insulin-dependent
      diabetes mellitus.
AB  - Over the past year, a number of important observations have been made in the
      nonobese diabetic mouse and in clinical insulin-dependent diabetes mellitus
      concerning the autoimmune response to islets. Assays have advanced to the point
      where individuals at risk for insulin-dependent diabetes mellitus can be readily
      identified prior to the onset of symptoms and a number of peptides of proteins
      expressed by the beta cell have been shown to protect nonobese diabetic mice from
      developing diabetes. The contributions of CD4+ and CD8+ T cells to beta cell
      destruction are beginning to be understood and this information will probably be
      of value in the design of intervention strategies for use in human subjects.

PMID- 8994868
TI  - Autoimmunity to ion-channels and other proteins in paraneoplastic disorders.
AB  - Paraneoplastic neurological disorders are rare conditions caused by immune
      responses against tumour antigens that cross-react with neuronal antigens. In the
      past year, there have been advances in the definition of some of the antigens
      that are recognized by patients' antibodies, and new observations on the results
      of passive and active immunization against the antigens.

PMID- 8994869
TI  - Cytokines in autoimmunity.
AB  - The past few years have witnessed exciting developments regarding the role of
      cytokines in autoimmune diseases, particularly in rheumatoid arthritis and
      Crohn's disease, with the demonstration that anti-TNF alpha therapy is clinically
      beneficial and provides reproducible results. Recent contributions to this field,
      derived from in vivo studies in animal models of autoimmunity, and increasingly
      from clinical trials, have greatly enhanced our understanding of this field.

PMID- 8994870
TI  - Virus-induced autoimmune disease.
AB  - The breaking of tolerance or unresponsiveness to self-antigens, involving the
      activation of autoreactive lymphocytes, is a critical event leading to autoimmune
      diseases. The precise mechanisms by which this can occur are mostly unknown.
      Viruses have been implicated in this process, among other etiological factors,
      such as genetic predisposition and cytokine activity. Several ways have been
      proposed by which a viral infection might break tolerance to self and trigger an
      autoreactive cascade that ultimately leads to the destruction of a specific cell
      type or an entire organ. The process termed "molecular mimicry' and the use of
      transgenic models in which viral and host genes can be manipulated to analyze
      their effects in causing autoimmunity have been particular focuses for research.
      For example, there is a transgenic murine model of virus-induced autoimmune
      disease, in which a known viral gene is selectively expressed as a self-antigen
      in beta cells of the pancreas. In these mice, insulin-dependent diabetes develops
      after either a viral infection, the release of a cytokine such as IFN-gamma, or
      the expression of the costimulatory molecule B7.1 in the islets of Langerhans.
      Recent studies using this model have contributed to the understanding of the
      pathogenesis of virus-induced autoimmune disease and have furthered the design
      and testing of novel immunotherapeutic approaches.

PMID- 8994871
TI  - Atopic allergy and other hypersensitivities.

PMID- 8994872
TI  - Autoimmunity.

PMID- 8994873
TI  - Structural and mechanistic studies of enolase.
AB  - The high-resolution structure of yeast enolase cocrystallized with its
      equilibrium mixture of substrate and product reveals the stereochemistry of
      substrate/product binding and therefore the groups responsible for acid/base
      catalysis and stabilization of the enolate intermediate. Expression and
      characterization of site-specific mutant forms of the enzyme have confirmed the
      roles of amino acid side chains in the catalysis of the first and second steps of
      the reaction. Coordination of both required magnesium ions to the carboxylate of
      the substrate/product indicates a role for these cations in stabilization of the
      intermediate.

PMID- 8994874
TI  - The relationship between structure and function for the sulfite reductases.
AB  - The six-electron reductions of sulfite to sulfide and nitrite to ammonia,
      fundamental to early and contemporary life, are catalyzed by diverse sulfite and
      nitrite reductases that share an unusual prosthetic assembly in their active
      centers, namely siroheme covalently linked to an Fe4S4 cluster. The recently
      determined crystallographic structure of the sulfite reductase hemoprotein from
      Escherichia coli complements extensive biochemical and spectroscopic studies in
      revealing structural features that are key for the catalytic mechanisms and in
      suggesting a common symmetric structural unit for this diverse family of enzymes.

PMID- 8994875
TI  - The structural basis of negative cooperativity: receptors and enzymes.
AB  - Crystal structures of the negatively cooperative aspartate receptor caught at
      intermediate stages in the binding process help to elucidate structural factors
      involved in ligand binding. The frequency of occurrence of negatively cooperative
      proteins suggests that sequential changes in binding patterns will be extensive
      in positively cooperative as well as in negatively cooperative and no
      cooperativity proteins.

PMID- 8994876
TI  - Control by phosphorylation.
AB  - The two examples of phospho and dephospho proteins for which structural data were
      previously available (glycogen phosphorylase and isocitrate dehydrogenase)
      demonstrated two different mechanisms for control. In glycogen phosphorylase,
      activation by phosphorylation results in long-range allosteric changes. In
      isocitrate dehydrogenase, inhibition by phosphorylation is achieved by an
      electrostatic blocking mechanism with no conformational changes. During the past
      year, the structures of the phospho and dephospho forms of two more proteins, the
      cell cycle protein kinase CDK2 and yeast glycogen phosphorylase, have been
      determined. The new results highlight the importance of the phosphoamino acids
      both in the organization of local regions of protein structure through phosphate
      arginine interactions and in the promotion of long-range conformational
      responses.

PMID- 8994877
TI  - Calcineurin-immunosuppressor complexes.
AB  - Crystal structures of the Ser/Thr phosphatase calcineurin (protein phosphatase
      2B) have recently been solved by X-ray crystallography, both in the free-protein
      state, and complexed with the immunophilin/immunosuppressant FKBP12/FK506. Core
      elements of the calcineurin phosphatase have been found to be similar to the
      corresponding elements of Ser/Thr phosphatase 1 and purple acid phosphatase. The
      structures provide a basis for understanding calcineurin inhibition by a ternary
      complex of immunophilin and immunosuppressant proteins.

PMID- 8994878
TI  - Muscle proteins--their actions and interactions.
AB  - Muscle contracts by the myosin cross-bridges "rowing' the actin filaments past
      the myosin filaments. In the past year many structural details of this mechanism
      have become clear. Structural studies indicate distinct states for myosin S1 in
      the rigor, ATP or "down' conformation and in the products complex (ADP.Pi) or
      "up' to state. Crystallographic studies substantiate this classification and
      yield details of the transformation. The isomerization "up' to "down' is the
      power stroke of muscle. This consists in the main of large changes of angle of
      the "lever arm' (at the distal part of the myosin head) which can account for an
      11 nm power stroke.

PMID- 8994879
TI  - The diverse world of coenzyme A binding proteins.
AB  - Coenzyme A is involved in a number of important metabolic pathways. Recently the
      structures of several coenzyme A binding proteins have been determined. We
      compare in some detail the structures of seven different coenzyme A protein
      complexes. These seven proteins all have distinctly different folds.

PMID- 8994880
TI  - Protein-biotin interactions.
AB  - The three-dimensional structures of several biotin-binding proteins are now
      known, giving insights into the molecular architecture of the binding sites for
      biotin. In combination with biochemical and computational approaches, these
      structural insights provide the basis for our present understanding of biotin
      protein interactions which, in some cases, give rise to spectacular binding
      constants.

PMID- 8994881
TI  - Novel metal sites in protein structures.
AB  - Recently, the three-dimensional structures of several novel metalloenzymes have
      been solved. Of special interest are those containing uncommon and/or not well
      characterized metals such as molybdenum, tungsten, nickel, vanadium and cobalt.
      Modulated by the protein environment, the specific properties of these metals and
      of special metal-binding cofactors such as siroheme and topa quinone are used to
      catalyze a vast array of fascinating reactions.

PMID- 8994882
TI  - The fascinating complexities of steroid-binding enzymes.
AB  - Enzymes that modulate the level of circulating steroid hormone can be used to
      combat steroid-dependent disorders. Members of the NADPH-dependent short chain
      dehydrogenase/reductase (SDR) family control blood pressure, fertility, and
      natural and neoplastic growth. Despite the fact that only one amino acid residue
      is strictly conserved in the 60 known members of the family, all appear to have
      the dinucleotide-binding Rossmann fold and homologous catalytic residues
      containing the conserved tyrosine. Variation in the amino acid composition of the
      substrate binding pocket creates specificity of binding for steroids,
      prostaglandins, sugars and alcohols. Licorice induces high blood pressure by
      inhibiting an SDR in the kidney, and appears to combat ulcers by inhibiting
      another in the stomach. Detailed X-ray analyses of various members of the family
      should allow the design of potent, tissue-specific, highly selective inhibitors.

PMID- 8994883
TI  - New structures of allosteric proteins revealing remarkable conformational
      changes.
AB  - New three-dimensional structures of allosteric proteins reveal they have a
      flexible architecture that is instrumental to the regulation of protein function.
      Highlights are the structures of GroEL, pyruvate kinase, D-3-phosphoglycerate
      dehydrogenase and the acetylcholine receptor. Furthermore, significant progress
      in understanding the nature of the intermediates involved in an allosteric
      reaction has been achieved through recent spectroscopic and crystallographic
      studies on haemoglobin.

PMID- 8994884
TI  - Sialidases: structures, biological significance and therapeutic potential.
AB  - The structure-based design of a potent inhibitor of the influenza-virus
      neuraminidase (sialidase) is one of the outstanding successes of rational drug
      design. Recent clinical trials of the drug have stimulated many companies to seek
      a share of the potentially huge flu market. Sialidases, however, are involved in
      the pathogenesis of a whole range of other diseases, so perhaps the knowledge and
      expertise gained from the influenza story can be used in the design of other
      drugs, given that they all share certain structural features.

PMID- 8994885
TI  - Protein-drug complexes important for immunoregulation and organ transplantation.
AB  - Recently, two structures of the Ser/Thr phosphorylase calcineurin in complex with
      FK506 and its cognate immunophilin, FKBP12, have been reported, both solved by
      small pharmaceutical companies focused on structure-based drug design. A
      realization, however, that the toxicities associated with calcineurin-mediated
      immunosuppressants might be mechanism based has driven the current interest in
      alternative approaches to autoimmunity prophylaxis and preventing transplant
      rejection. Regulatory approval in 1995 of the immunosuppressant prodrug
      mycophenolate mofetil, whose active metabolite, mycophenolic acid, inhibits
      inosine monophosphate dehydrogenase, has focused attention on the potential
      significance of the de novo purine-biosynthesis pathway as a target for
      immunosuppressive drugs, leading ultimately to the solution of enzyme structure
      as a drug design target. As this and other clinically relevant targets are
      discovered, elaborated and refined via the activity of their cognate agents (as
      was the case for the phosphatase calcineurin via the activity of cyclosporin), a
      critical opportunity should ensue for structural biology to exert a profound
      effect on the future development of these therapies.

PMID- 8994886
TI  - Glutamine repeats and inherited neurodegenerative diseases: molecular aspects.
AB  - Several dominantly inherited, late onset, neurodegenerative diseases are due to
      expansion of CAG repeats, leading to expansion of glutamine repeats in the
      affected proteins. These proteins are of very different sizes and, with one
      exception, show no sequence homology to known proteins or to each other; their
      functions are unknown. In some, the glutamine repeat starts near the N-terminus,
      in another near the middle and in another near the C-terminus, but regardless of
      these differences, no disease has been observed in individuals with fewer than 37
      repeats, and absence of disease has never been found in those with more than 41
      repeats. Protein constructs with more than 41 repeats are toxic to E. coli and to
      CHO cells in culture, and they elicit ataxia in transgenic mice. These
      observations argue in favour of a distinct change of structure associated with
      elongation beyond 37-41 glutamine repeats. The review describes experiments
      designed to find out what these structures might be and how they could influence
      the properties of the proteins of which they form part. Poly-L-glutamines form
      pleated sheets of beta-strands held together by hydrogen bonds between their
      amides. Incorporation of glutamine repeats into a small protein of known
      structure made it associate irreversibly into oligomers. That association took
      place during the folding of the protein molecules and led to their becoming
      firmly interlocked by either strand- or domain-swapping. Thermodynamic
      considerations suggest that elongation of glutamine repeats beyond a certain
      length may lead to a phase change from random coils to hydrogen-bonded hairpins.
      Possible mechanisms of expansion of CAG repeats are discussed in the light of
      looped DNA model structures.

PMID- 8994887
TI  - Catalysis and regulation.

PMID- 8994888
TI  - Proteins.

PMID- 8994889
TI  - Overview of methodologic issues for pharmacologic trials in mild, moderate, and
      severe Alzheimer's disease.
AB  - To address the issue of mild, moderate, and severe Alzheimer's disease (AD), it
      is necessary to initially establish some agreement on terminology. In recent
      decades, these terms have frequently been defined using screening instrument
      scores with measures such as the Mini-Mental State Examination (MMSE). There are
      many problems with this approach, perhaps the most salient of which is that it
      has contributed to the total and tragic neglect of patients with severe AD. An
      alternative approach to the classification of AD severity is staging. This
      approach has advanced to the point where moderately severe and severe AD can be
      described in detail. Procedures for describing this previously neglected latter
      portion of AD have recently been extensively validated. Staging is also uniquely
      useful at the other end of the severity spectrum, in differentiating early aging
      brain/behavior changes, incipient AD, and mild AD. Temporally, with staging
      procedures, it is possible to track the course of AD approximately three times
      more accurately than with the MMSE. The net result of the advances in AD
      delineation is that issues such as prophylaxis, modification of course, treatment
      of behavioral disturbances, loss of ambulation, progressive rigidity, and the
      development of contractures in AD patients can now be addressed in a
      scientifically meaningful way that will hopefully bestow much benefit in AD
      patients and those who care for them.

PMID- 8994890
TI  - The Alzheimer's Disease Assessment Scale.
AB  - This article reviews longitudinal data collected from patients with Alzheimer's
      disease (AD) that are relevant to the design and interpretation of clinical
      treatment trials. Longitudinal data from patients tested with the Alzheimer's
      Disease Assessment Scale demonstrate that cognitive symptoms, including memory
      loss, dysphasia, and dyspraxia, worsen relentlessly over time with the rate of
      change depending upon baseline dementia severity. Noncognitive symptoms, such as
      agitation, depressed mood, and psychosis, are episodic, do not necessarily worsen
      over time, and tend not to be highly correlated with one another. The reliability
      of cognitive change measures increases with follow-up duration so that the
      likelihood of detecting drug effects on the rate of cognitive deterioration is
      greater with longer treatment trials. Functional measures of activities of daily
      living are difficult to standardize for AD patients but are important for
      determining the overall clinical and economic impact of AD treatments.

PMID- 8994891
TI  - The Hierarchic Dementia Scale: conceptualization.
AB  - The Hierarchic Dementia Scale is an instrument for measuring the severity of
      mental impairment based on Piagetian concepts, neuropsychological findings, and
      the hierarchic nature of decline in mental function. Performance of 20 specific
      functions such as orienting reflexes and comprehension can be rapidly pinpointed
      over a wide range of impairment. The scale is reliable, valid, responsive, safe,
      inexpensive, and easy to use.

PMID- 8994892
TI  - The Hierarchic Dementia Scale: usage.
AB  - The reliability, validity, and sensitivity to change of the Hierarchic Dementia
      Scale (HDS) were tested in two cross-sectional studies and one longitudinal
      study. Results prove the HDS to be a simple-to-conduct method, economical in
      terms of time, and possessing high reliability and high concurrent and criterion
      related validity. The HDS appears capable of use at all stages of dementia and
      capable of permitting studies of the course well into the advanced stages of the
      illness.

PMID- 8994893
TI  - Reliability of the Modified Ordinal Scales of Psychological Development: a
      cognitive assessment battery for severe dementia.
AB  - Two reliability studies were performed on a recently developed cognitive
      assessment battery for severe dementia. The method, the Modified Ordinal Scales
      of Psychological Development (M-OSPD), is based on the Piagetian developmental
      model of sensorimotor functions. Procedures have been adapted from this test
      battery, which was originally applied to infants and small children, for the
      assessment of remaining cognitive capacity in severe dementia. Two independent
      interrater reliability studies were conducted. In these studies, two different
      raters simultaneously evaluated patients with severe dementia. One interrater
      reliability study was performed in a nursing home setting (Study 1), and the
      other reliability study consisted of a sample of community-residing patients
      (Study 2). The Global Deterioration Scale and the Mini-Mental State Examination
      were used to assess dementia severity. Study 1 (N = 22) resulted in an intraclass
      correlation coefficient (ICC) of .99 (p < .01) for the M-OSPD total score. Study
      2 (N = 19) resulted in an ICC of .96 (p < .01) for the M-OSPD total score. The M
      OSPD proved to be a reliable instrument in these studies. This cognitive
      assessment measure can provide meaningful information regarding the cognitive
      abilities of late-stage dementia patients. Until recently, these late-stage
      dementia patients had been considered untestable in studies that utilized
      conventional psychometric and mental status evaluation measures.

PMID- 8994894
TI  - Assessment of agitation.
AB  - Agitation is inappropriate verbal, vocal, or motor activity, which is common
      among older persons with dementia. Its assessment is complicated both by
      communication difficulties and by the complexity of the manifested behaviors.
      Three general approaches are used to assess agitation: informant ratings,
      observational methods, and technological devices. Within each category, several
      assessment instruments exist. The approaches differ as to time sampling,
      objectivity, and cost. Assessment of agitation in pharmacological studies should
      include consideration of the specific meaning to the agitated behavior for the
      older person and for the caregiver, along with an evaluation of the consequences
      of the behavior. At times, the agitated behavior seems to signal a specific need,
      and alternative methods for fulfilling that need should be considered. Evaluation
      studies of pharmacologic agents should include consideration of the impact of
      these agents on nontarget behaviors, as well as an awareness of the large
      intraperson and interperson variability in agitated behaviors.

PMID- 8994895
TI  - The Empirical Behavioral Pathology in Alzheimer's Disease (E-BEHAVE-AD) Rating
      Scale.
AB  - A clinician should not rely entirely upon a caregiver's report regarding
      behavioral pathology when planning a treatment strategy. Direct observational
      evaluation instruments as well as caregiver-based assessments are necessary. A
      new scale for the empirical (observational) evaluation of behavioral symptoms in
      Alzheimer's disease (AD) and related dementias, the Empirical Behavioral
      Pathology in Alzheimer's Disease Rating Scale (E-BEHAVE-AD) was developed.
      Interrater reliability of this new assessment instrument was examined.
      Additionally, the relationship between the observed occurrence of behavioral
      symptomatology on this new rating instrument was compared with the occurrence
      using a similarly designed, caregiver-based instrument. The interrater
      reliability study consisted of two raters who simultaneously evaluated 20
      dementia patients. The comparative study employed a cross-sectional design (N =
      49). Individuals were evaluated in an outpatient clinic setting. The study
      population consisted of cognitively normal individuals and dementia patients.
      Evaluations included the new, observationally based behavioral assessment (the E
      BEHAVE-AD), a caregiver-based behavioral assessment (the Behavioral Pathology in
      Alzheimer's Disease Rating Scale; BEHAVE-AD), a clinical global measure (the
      Global Deterioration Scale), and a mental status assessment (the Mini-Mental
      State Examination). The interrater reliability study revealed an intraclass
      correlation coefficient of .97 (p < .01) for total scores on the new E-BEHAVE-AD
      rating scale. The correlation coefficient for the amount of agreement on the
      presence of symptoms in six symptomatic categories between caregiver-based
      information about the patient's behavioral pathology assessed on the BEHAVE-AD
      and the clinician's observations assessed with the new E-BEHAVE-AD rating
      instrument was .51 (p < .01). The new E-BEHAVE-AD rating instrument showed
      excellent interrater reliability. Furthermore, there was a statistically
      significant relationship between clinician observation of the occurrence of
      behavioral pathology assessed using the E-BEHAVE-AD and caregiver-reported
      pathology assessed with the BEHAVE-AD. However, the magnitude of the correlation
      between these measures indicated that the majority of variance was independent
      and nonoverlapping. Consequently, these data support theoretical models
      suggesting that the assessment of behavioral pathology in dementia might ideally
      encompass both direct observational and caregiver-report approaches, using
      measures such as the E-BEHAVE-AD as well as measures such as the BEHAVE-AD.

PMID- 8994896
TI  - Assessment of quality of life: preservation of the self.
AB  - To understand the quality of life of persons with Alzheimer's disease (AD), it is
      necessary for investigators to examine the perspective of the victim of the
      disease. This requires more than assessment of memory and function; qualitative
      changes in quality of life as expressed by successful, adaptive, and problem
      behaviors need to be measured. The latter are often expressions of emotional
      distress that, if properly understood, may allow observers to appreciate the
      experience of AD from the patient's perspective. Such an approach provides a
      greater likelihood of preserving "the self" of the patient during intervention.

PMID- 8994897
TI  - Clinical global impressions in Alzheimer's clinical trials.
AB  - This article reviews the history of Clinical Global Impressions of Change (CGIC)
      instruments, their use and limitations in clinical trials of Alzheimer's disease,
      and the development of the National Institute on Aging's Alzheimer's Disease
      Cooperative Study-Clinical Global Impression of Change Scale (ADCS-CGIC).
      Originally, CGICs were simple and unstructured instruments that asked a clinician
      to rate change over the duration of a clinical trial. The method, however, failed
      to consistently detect treatment effects, leading to the development of more
      structured and subsequently validated approaches, such as the Clinician Interview
      Based Impression Scale (CIBI) and the ADCS-CGIC. Both are currently used in
      clinical trials. The implications and importance of choosing an appropriate
      global rating are discussed.

PMID- 8994899
TI  - Feed intake pattern during lactation and subsequent reproductive performance of
      sows.
AB  - Daily feed intake during lactation was recorded for 20,296 lactating sows on 30
      commercial farms in the United States. Each lactation feed record was categorized
      into one of six patterns: RAPID, rapid increase in feed intake; MAJOR, major
      drop; MINOR, minor drop; LLL, low feed intake throughout lactation; LHH, low
      intake during the 1st wk then an increase in feed intake for the remainder of
      lactation; and GRADUAL, gradual increase. A database containing 24,340 farrowing
      records and 19,015 subsequent litter records were abstracted from the PigCHAMP
      data files of the farms enrolled in the study. Multiple regression analyses
      revealed that ADFI during lactation had nonlinear or linear associations with
      weaning-to-first service interval (WSI), weaning-to-conception interval (WCI),
      litter weight at weaning (WWT), and subsequent litter size (SLS). Sows having LLL
      and LHH had longer (P < .01) WSI and WCI than the other patterns. Sows with MAJOR
      had a longer WCI (P < .05) than females with RAPID. Further, sows having MAJOR
      had lighter (P < .01) WWT than those with RAPID, MINOR, and GRADUAL. Sows having
      MAJOR had a higher (P < .01) proportion of females culled for anestrus relative
      to RAPID. Furthermore, sows exhibiting a drop in feed intake in either wk 1 or 2
      were more likely to be culled for anestrus than sows having no drop. These
      results suggest that both the amount and pattern of feed intake during lactation
      influence subsequent reproductive performance.

PMID- 8994898
TI  - Mortality and temporal course of probable Alzheimer's disease: a 5-year
      prospective study.
AB  - Alzheimer's disease (AD) is associated with an increased mortality in comparison
      with aged control populations. The relationship between the clinical and the
      temporal course of AD has not been well studied over significant intervals.
      Community-residing patients with probable AD (N = 103, 42 men, mean age = 70.2 +/
      8.0 years) were studied at baseline on demographic and clinical variables,
      including measures of global deterioration (Global Deterioration Scale; GDS),
      mental status and cognition (e.g., Mini-Mental State Examination; MMSE), and
      functional impairment (Functional Assessment Staging; FAST). Baseline
      characteristics included a GDS range of Stage 4, 5, or 6 (38.8%, 39.8%, and
      21.4%, respectively) and a mean MMSE score of 15.4 +/- 5.6. The mean follow-up
      interval was 4.6 +/- 1.4 years. Follow-ups were done blind to baseline measures
      and when necessary were conducted in residential and nursing home settings. Of
      locatable subjects (n = 95, 92%), 30 (31.6%) were decreased. Survivors (n = 65)
      had a mean GDS stage of 6.2 +/- 0.9 and a mean MMSE score of 5.1 +/- 6.9; 51% had
      MMSE scores of 0. Increased age and male gender, but not baseline clinical
      dementia variables, increased the risk of death (ps < .01). Change in clinical
      variables correlated significantly with time elapsed (r = .32, p < .05, for MMSE
      change, to r = .48, p < .001, for GDS change). Significant variance in temporal
      change (i.e., time elapsed) was accounted for by change in two of the five
      clinical measures studied (i.e., GDS and FAST; multiple r = .53). The results
      support previous estimates of mean duration of the GDS and FAST stages. For
      subjects with probable AD followed over approximately 5 years, clinical variables
      changed significantly over time in survivors. However, the majority of temporal
      variance in the course of AD remains unexplained.

PMID- 8994900
TI  - Effect of interval from melengestrol acetate to prostaglandin F2 alpha on timed
      and synchronized pregnancy rates of beef heifers and cows.
AB  - The objective of this experiment was to determine the optimal interval from the
      last day of melengestrol acetate (MGA) feeding to prostaglandin F2 alpha (PGF2
      alpha) treatment on pregnancy rates of beef heifers and cows. All females (149
      heifers and 399 postpartum cows) were fed MGA (.5 mg) daily for 14 d and then
      administered PGF2 alpha (25 mg Lutalyse) 13, 15, and 17 d (Groups 1, 2, and 3,
      respectively) after the last day of MGA feeding. Females not in estrus the first
      52 h after PGF2 alpha treatment were artificially inseminated 72 h after PGF2
      alpha treatment. Females in estrus 0 to 52 h and 78 h to 6 d after PGF2 alpha
      treatment were inseminated at estrus. Blood sera (collected immediately before
      and 3 d after PGF2 alpha treatment) were assayed for progesterone concentrations.
      Pregnancy was determined 44 to 47 d after the 72-h AI by rectal examination. The
      intervals from MGA feeding to PGF2 alpha that had the highest 72-h AI pregnancy
      rates were 17 d for heifers (43%) and 15 d for cows (43%). Heifers with a 17-d
      interval had a higher (P < .05) 72-h AI pregnancy rate than heifers with 13-d and
      15-d intervals, and cows with a 15-d interval had a higher (P < .05) 72-h AI
      pregnancy rate than cows with a 17-d interval. The 4-d synchronized pregnancy
      rates (the 72-h AI and the succeeding 3 d inseminations) for both heifers (44%)
      and cows (53%) were not different (P > .05) among groups. Fewer (P < .05) cows
      with a 17-d interval from MGA to PGF2 alpha had corpora lutea regression (by 72
      h) after PGF2 alpha treatment than cows with 13-d and 15-d intervals. We
      interpret the results to indicate that the interval from MGA to PGF2 alpha
      treatment may influence 72-h AI pregnancy rates, that optimal intervals are 17 d
      for heifers and 15 d for cows, and that pregnancy rates are improved by
      insemination for 3 d after the 72-h AI.

PMID- 8994901
TI  - Blood selenium concentrations in cows and heifers on 253 cow-calf operations in
      18 states.
AB  - This study was conducted to determine the geographic distribution of selenium
      deficiency among beef cows and heifers in selected states. Whole blood selenium
      concentrations were determined for cows and heifers on 253 cow-calf operations in
      18 states. Overall, 7.8% of the samples were severely deficient, and another
      10.4% of the samples were considered marginally deficient for selenium. Blood
      selenium concentrations varied by geographic region. Cattle from the southeastern
      states were more commonly considered severely or marginally deficient (18.6% and
      23.8%, respectively) than cattle from other regions. Herds from the southeastern
      states were also more commonly considered severely or marginally deficient (14.9%
      and 20.9%, respectively) than herds from other regions. Blood selenium
      concentration also varied by whether selenium had been supplemented to the herd.
      We conclude that blood selenium levels for cattle vary by geographic region and
      selenium supplementation of the herd.

PMID- 8994902
TI  - Effect of salinomycin on giardiasis and coccidiosis in growing lambs.
AB  - An experiment was undertaken to determine the effect of salinomycin on Giardia in
      vitro and on Giardia and coccidia in growing lambs. Concentrations of salinomycin
      above (3.9 micrograms/mL) reduced the adherence (index of viability) of Giardia
      S2 trophozoites by more than 50%. This strain did not develop resistance after
      repeated exposure to sublethal concentrations of salinomycin. Five of 40 lambs
      escaped natural infection by Giardia, and these were inoculated with > or =
      500,000 cysts. Giardiasis (presence of cysts in feces) was confirmed in all lambs
      before commencement of the experiment. Coccidiosis (presence of oocysts)
      developed by natural exposure. Lambs were assigned randomly to diets containing
      0, 4, 10, or 16 ppm of salinomycin. Giardia cyst and coccidia oocyst excretions
      were determined on 6 d during the first week and weekly thereafter. Giardia cysts
      were detected at each sampling date in all treatments (highest release, 2.3 x
      10(6) cysts/g feces). The number of Giardia cysts shed in feces was not affected
      (P > .05) by salinomycin but did decline (P < .05) with time. Average infection
      rates remained above 50% until d 41 of the experiment and declined linearly (P <
      .05) with salinomycin concentration and time. The number of coccidia oocysts in
      feces was low (highest release, 6.8 x 10(4) oocysts/g feces), but shedding
      occurred in 38 of the 40 lambs. Treatment with salinomycin had a cubic effect (P
      < .05) on coccidia oocyst excretion, and no oocysts were detected beyond d 28.
      Treatment effect on average daily gain (P < .002), dry matter intake (P < .02),
      and final live weight (P < .07) was cubic, whereas carcass weight (P < .003) and
      dressing percentage (P < .08) were linearly affected by salinomycin
      concentration. Although a beneficial effect of 10 ppm salinomycin on lamb
      performance was apparent, the development of natural resistance makes it
      difficult to attribute this response to the control of coccidiosis or giardiasis.

PMID- 8994904
TI  - Characterization of dose-dependent metabolic responses to close arterial infusion
      of cimaterol in the hindlimb of steers.
AB  - Dose-dependent effects of cimaterol (CIM) on hindlimb metabolism were determined
      in six steers (247 +/- 22 kg BW) using a close arterial infusion. The external
      iliac vessels of both hindlimbs were catheterized to accommodate measurement of
      blood flow, circulating concentrations, and net flux of NEFA, lactate, and alpha
      amino nitrogen (AAN) during infusion of CIM at 0, .05, .1, .3, .7, 1 and 3
      micrograms/ min. Close arterial infusion of CIM in the hindlimb of steers can be
      used to achieve a local concentration elevation that is required to differentiate
      local and systemic effects in vivo. Calculated plasma threshold CIM concentration
      required to initiate cardiovascular responses was 21 pg/mL, which resulted from
      an infusion rate of .3 microgram/min. Threshold concentrations of CIM for
      stimulation of NEFA and lactate net flux in the hindlimb were 38 and 34 pg/mL,
      respectively, and would be achieved with an infusion rate of .7 microgram/min.
      All measured responses except AAN net flux exhibited significant linear and
      quadratic dose effects, and responses in the treated hindlimb were always
      severalfold greater than in the contralateral control hindlimb. Maximal
      differences between treated and control hindlimb blood flow occurred with a CIM
      infusion rate of .7 microgram/min, but the highest infusion rate (3
      micrograms/min) was required to maximize differences in NEFA and lactate flux.
      Therefore, to minimize cardiovascular and other systemic responses and optimize
      direct hindlimb responses, an infusion rate of .5 microgram of CIM/ min should
      cause significant stimulation of beta-adrenergic receptors only in the CIM
      infused hindlimb of young, growing steers.

PMID- 8994903
TI  - Technical note: use of a PCR-single strand conformation polymorphism (PCR-SSCP)
      for detection of a point mutation in the swine ryanodine receptor (RYR1) gene.
AB  - We used the polymerase chain reaction-single strand conformation polymorphism
      (PCR-SSCP) analysis for screening the point mutation (C1843 to T) in the porcine
      ryanodine receptor (RYR1) gene. The PCR products (659 bp) were heat-denatured and
      separated by polyacrylamide gel electrophoresis. On silver-stained gels, the
      point mutation within the RYR1 gene could be detected clearly by mobility shifts.
      The best conditions for detecting the point mutation were by using a 5%
      polyacrylamide gel without glycerol and loading at 3 degrees C. The RYR1
      genotypes diagnosed by PCR-SSCP were identical to the genotypes diagnosed by
      restriction enzyme fragment length polymorphism in all cases examined (n = 606).

PMID- 8994905
TI  - Effects of Synovex-S and recombinant bovine growth hormone (Somavubove) on growth
      responses of steers: I. Performance and composition of gain.
AB  - The influence of Synovex-S (SYN) ear implant (200 mg progesterone and 20 mg
      estradiol benzoate) and Somavubove (SbV) recombinant bovine growth hormone (.1
      mg/kg BW i.m., daily) on live animal performance, tissue growth, and the
      partitioning of energy gain was determined using a slaughter-balance protocol
      with 25 young MARC II x (Angus-Hereford crossbred) beef steers (initial BW 182 +/
      1.8 kg). Following 21 d of adjustment to individual pens and to a diet of 80%
      concentrate and 20% corn-grass (1:1) silages, five groups of five steers per
      group were assigned to initial slaughter or a 2 x 2 factorial arrangement of
      treatments of CTL (no implant + daily placebo i.m. injection of bicarbonate
      saline), SYN (implant + placebo), SbV, or SYN + SbV and slaughtered at 56 d on
      treatment. Steers were fed (per kilogram BW.75 daily) 20 g of CP and 252 Kcal of
      ME and consumed 5.5 +/- .07 kg/d DM across treatments. Empty body and carcass
      gains were affected (SYN, P < .01; SbV, P < .01) by treatments (CTL, SYN, SbV,
      and SYN + SbV: 1.26, 1.43, 1.63, 1.78 kg/d, SEM = .05, and .78, .97, .97, 1.08
      kg/d, SEM = .04, respectively). Noncarcass gain was .45, .48, .60, and .60 kg/d
      (SEM = .03; SbV, P < .01). For empty body, both protein and water gains were
      greater for SYN-implanted steers (P < .05) than for steers not implanted and for
      SbV-injected steers (P < .01) than for placebo-injected steers. Treatments did
      not influence the efficiency of energy gain. The proportional amount of energy
      deposited as protein was greater (P < .01) for SbV-injected steers than for
      placebo-injected steers. The proportional amount of protein deposited was not
      influenced by SYN (P > .10); however, means were numerically greater for SYN
      implanted steers than for steers not implanted, the largest mean being for the
      SYN + SbV treatment group. Somavubove increased (P < .01) the efficiency of
      energy deposited as protein in both the empty body and carcass compared with
      steers not receiving SbV. Efficiency of energy deposited as protein in the empty
      body tended to be greater (P < .10) for SYN-implanted steers than for steers not
      implanted. The efficiency with which total feed energy was deposited as protein
      in empty body was 10% greater for the SYN group than for the CTL group, 21%
      greater for the SbV group than for the CTL group, and 37% greater for the
      combined SYN + SbV treatment than for the CTL group. The data from this study are
      interpreted to indicate that SYN and SbV act in an additive manner to improve
      growth and protein deposition in young growing steers.

PMID- 8994906
TI  - Effects of Synovex-S and recombinant bovine growth hormone (Somavubove) on growth
      responses of steers: II. Muscle morphology and proximate composition of muscles.
AB  - Twenty crossbred beef steers (initial BW 182 +/- 1.8 kg) were used in a 2 x 2
      factorial to determine the effects of implantation with Synovex-S (SYN; 20 mg 17
      beta estradiol benzoate + 200 mg progesterone, ear implant) and administration of
      recombinant bovine growth hormone (Somavubove SbV, .1 mg.kgBW-1.d-1, i.m.) on the
      morphology of six muscles (longissimus, psoas major, supraspinatus, triceps
      brachii, semitendinosus, rectus femoris) of growing steers. Implantation with SYN
      decreased the percentage distribution of FOG fibers and increased FG fibers in
      the supraspinatus and rectus femoris muscles (P < .05). Steers treated with SYN
      had a larger area of SO and FG fibers in the psoas major muscle (P < .05). The
      administration of SbV decreased the percentage distribution of FOG fibers and
      increased FG fibers in the rectus femoris muscle (P < .05). Steers administered
      SbV had larger SO, FOG, and FG fibers in the psoas major muscle and SO fibers in
      the supraspinatus and semitendinosus muscles (P < .05). The combined
      administration of SYN and SbV had minimal, if any, effect on the percentage
      distribution of fiber types (P > .05) but increased (P < .05) the fiber areas of
      all muscles (18.5 to 54.8%) except the rectus femoris (P > .05). Proximate
      composition of the muscles was generally not affected (P > .05) by any of the
      treatments. The only observations were decreases in fat content for psoas major
      and rectus femoris muscles as a result of the combined administration of SYN and
      SbV. These results indicate that both growth-promoting agents, SYN and SbV, have
      potential to increase muscle fiber size, but muscles respond differently to the
      administrations of SYN and SbV. However, when SYN and SbV are administered in
      combination, the combined effects result in an additive increase in muscle fiber
      hypertrophic response.

PMID- 8994907
TI  - Meat toughening does not occur when rigor shortening is prevented.
AB  - The objective of this experiment was to test the hypothesis that meat toughening
      during the first 24 h postmortem results from sarcomere shortening during rigor
      mortis development. Eleven market-weight lambs were used to measure changes in
      shear force of clamped longissimus during rigor development. Within 15 min of
      exsanguination, while attached at both ends, each longissimus was separated from
      the vertebrae body and clamped between three sets of metal plates to prevent
      muscle shortening (six clamped sections per lamb). Five of the clamped sections
      were placed at -1.1 degrees C for 0, 3, 6, 12, or 24 h. After storage at their
      respective times at -1.1 degrees C, the samples were placed at -30 degrees C for
      90 min and then at -5 degrees C for 8 d. The sixth section (168-h section) was
      stored at -1.1 degrees C for the first 24 h, at 4 degrees C for 144 h, and then
      treated the same as other sampling times. Sections were sampled for pH, sarcomere
      length, shear force, and Western blot analyses before and after storage at -5
      degrees C. Shear force values were the same (P > .05) from 0 to 24 h (4.5 kg at 0
      h to 4.9 kg at 24 h) then declined (P < .05) to 3.3 kg at 168 h postmortem. As
      evident by lack of statistical difference in the sarcomere lengths, we were
      successful in holding the muscle length constant. Western blot analyses of
      nebulin, vinculin, and troponin-T indicated that minimum degradation occurred
      through 12 h, was slightly increased by 24 h, and was relatively extensive by 168
      h postmortem. Although limited proteolysis occurred during storage at -5 degrees
      C for 8 d, this by itself had no effect on shear force. Results indicate that
      shear force values do not increase during rigor development when muscle is
      prevented from shortening; thus, the toughening that occurs during the first 24 h
      of slaughter is most likely due to sarcomere shortening.

PMID- 8994908
TI  - Collagen crosslinks in longissimus muscle from lambs expressing the callipyge
      gene.
AB  - The objective of this study was to determine whether increased amounts of
      collagen and (or) hydroxylysylpyridinoline crosslinks in longissimus muscle are
      partially responsible for decreased tenderness when callipyge lambs are compared
      to normal lambs. The longissimus muscle was used because we believe tenderness is
      a greater problem in loin chops of callipyge lambs than it is in other cuts. Ten
      normal and 10 half-sibling lambs expressing the callipyge gene were compared.
      Lambs were slaughtered at approximately 8 mo of age when they reached a target
      weight of 59 kg. Dressing percentages were higher for the leaner callipyge lambs
      that exhibited larger longissimus muscle areas and heavier leg weights (P < .01).
      Warner-Bratzler shear values for longissimus muscle from callipyge lambs were
      higher (P < .01) than those from normal lambs. The higher shear values were not
      explained by amount of muscle collagen or by hydroxylysylpyridinoline crosslink
      concentration because both collagen percentage (P < .09) and crosslink
      concentration (P < .04) were lower in callipyge lambs. Therefore, attempts to
      modify shear values and make loin chops from callipyge lambs more acceptable to
      consumers should focus on the myofibrillar fraction of muscle.

PMID- 8994909
TI  - Effect of feeding a milk replacer to early-weaned pigs on growth, body
      composition, and small intestinal morphology, compared with suckled littermates.
AB  - Feeding of milk replacer to early-weaned pigs was evaluated in two experiments.
      In Exp. 1, 18 litters of pigs were either weaned conventionally (d 21), split
      weaned and fed milk replacer plus starter diet (d 14 and 21), or weaned and fed
      milk replacer plus starter diet (d 21). Split weaning combined with feeding a
      milk replacer increased ADG 22% from d 14 and d 28 compared to conventional
      weaning (P < .05). Feeding a milk replacer plus starter diet after weaning
      increased ADG 30% between d 21 and 28 compared to conventional weaning (P < .01).
      In Experiment 2, four litters of 12 pigs each were divided at d 18 into six heavy
      and six light pigs and randomized across sow-suckled, milk replacer, or starter
      diet groups. After 1 wk, pigs fed milk replacer weighed 20% more (P < .001),
      contained 10% more protein (P < .01) and 17% more fat (P < .05), and had 74%
      longer villi in the proximal small intestine (P < .001) than suckled pigs. In
      contrast, pigs fed starter diet weighed 19% less (P < .001), contained 20% less
      protein and fat (P < .001), and had 28% shorter villi in the proximal small
      intestine (P < .05) than suckled pigs. Therefore, milk replacer feeding the 1st
      wk after weaning stimulates pig development, both locally in the small intestine
      and on a whole-body basis, most likely by an increased energy and nutrient
      intake. Suckling beyond 18 d postnatally inhibits pigs to reach maximal potential
      weight gain. In conclusion, milk replacer feeding might be beneficial to reach
      maximal pig weight gain at weaning.

PMID- 8994910
TI  - Efficacy of supplemental 1 alpha-hydroxycholecalciferol and microbial phytase for
      young pigs fed phosphorus- or amino acid-deficient corn-soybean meal diets.
AB  - Young pigs (5 wk of age and 8 kg) were used to test the efficacy of 1 alpha
      hydroxycholecalciferol (1 alpha-OH D3) and microbial phytase for improving the
      utilization of phytate phosphorus (P) and amino acids present in corn-soybean
      meal (SBM) diets. Phytase supplementation (1,200 units/kg) to a vitamin D3
      adequate, P-deficient corn-SBM diet elicited a marked response (P < .05) in
      weight gain and ash content of fibula, scapula, and metatarsal bones, but dietary
      addition of 1 alpha-OH D3 (20 micrograms/kg) was without effect. A P- and vitamin
      D3-adequate, amino acid-deficient corn-SBM diet (15.5% CP) also was supplemented
      with 1,200 units/kg of phytase to evaluate the efficacy of phytase in improving
      amino acid utilization. Pigs gained faster (P < .05) and more efficiently (P <
      .05) when this diet was supplemented with limiting amino acids, and phytase
      addition also increased (P < .05) weight gain, regardless of whether the diet was
      deficient or adequate in amino acids. Feed efficiency was improved (P < .05) by
      phytase addition to the amino acid-deficient diet but not to the amino acid
      adequate diet. Pigs fed the low-CP, amino acid-fortified diet gained as fast and
      as efficiently as those fed a 19.5% CP (1.19% lysine) positive-control diet.

PMID- 8994911
TI  - Evaluating the efficacy of selenium-enriched yeast and sodium selenite on tissue
      selenium retention and serum glutathione peroxidase activity in grower and
      finisher swine.
AB  - Three experiments conducted with grower-finisher pigs evaluated sodium selenite
      and a Se-enriched yeast source at various dietary Se levels on Se retention,
      tissue and serum Se concentrations, and serum glutathione peroxidase (GSH-Px)
      activity. Experiment 1 was a balance trial conducted in a 2 x 3 factorial
      arrangement in a randomized complete block (RCB) design in six replicates. Both
      Se sources were added at .1, .3, or .5 ppm Se. Crossbred barrows (n = 36)
      averaging 35.9 kg BW were placed in individual metabolism crates and fed their
      treatment diets, with feces and urine collected for a 7-d test period. Selenium
      retention increased as dietary Se levels increased, particularly when the Se
      enriched yeast was provided, resulting in a Se source x Se level interaction (P <
      .01). As dietary Se levels increased, urinary Se increased more when pigs were
      fed sodium selenite, whereas fecal Se increased more when the Se-enriched yeast
      was fed; both excretion routes resulting in Se level x Se source interaction
      responses (P < .01). Experiments 2 and 3 were conducted as RCB involving grower
      (n = 210) and finisher (n = 266) pigs, respectively, and evaluated the two Se
      sources each at .1, .3, or .5 ppm Se with a non-Se-fortified basal diet serving
      as a negative control. In Exp. 2, pigs were fed their treatment diets from 22.2
      to 60 kg BW in five replicates, whereas in Exp. 3 diets were fed from 65.8 to 105
      kg BW in six replicates. Grower pigs fed sodium selenite had serum GSH-Px
      activity that reached a plateau at .1 ppm Se and .3 ppm when the Se-enriched
      yeast source was fed, but the interaction response was not significant (P < .15).
      During the finisher period, serum GSH-Px activity reached a plateau at .1 ppm Se
      for both Se sources. Serum Se concentrations were lower at .1 ppm Se when the Se
      enriched yeast source was fed, resulting in a source x level interaction response
      for both grower (P < .05) and finisher (P < .01) periods. Loin Se contents were
      higher in grower and finisher pigs as dietary Se levels increased when the Se
      enriched yeast was fed, resulting in a Se source x Se level interaction (P <
      .01). The results suggest that more Se was retained in muscle tissue when the Se
      enriched yeast source was fed, that serum GSH-Px activity reached a plateau at
      approximately .1 ppm Se, and that sodium selenite may be more biologically
      available for GSH-Px activity than the Se-enriched yeast source.

PMID- 8994912
TI  - Influence of weaning age and nursery diet complexity on growth performance and
      carcass characteristics and composition of high-health status pigs from weaning
      to 109 kilograms.
AB  - We examined the influence of weaning age (9 or 19 +/- 1 d) and nursery diet
      complexity on growth performance and carcass composition of 192 high-health
      status barrows from weaning to 109 kg. Pigs were fed diets of different
      complexity (high, medium, or low) in various regimens from weaning to 18.7 kg.
      They then were fed common corn-soybean meal-based diets from 18.7 to 109 kg.
      Increasing diet complexity improved ADG from weaning to 7.0 kg (P < .10) but had
      no effect (P > .10) from 7.0 to 18.7 kg. Thus, increasing diet complexity seems
      to improve ADG only in the early period after weaning. Age at 109 kg was similar
      (P > .10) for the pigs weaned at 9 and 19 d. However, pigs fed the medium
      complexity regimens were the youngest (P < .01) at 109 kg. Interactions (P < .06)
      were observed for carcass lipid and lipid:protein accretion from 18.7 to 109 kg.
      These were the result of pigs weaned at 9 d of age having higher carcass lipid
      and lipid:CP accretion rates when fed the low-complexity regimens than when fed
      the medium- or high-complexity regimens. However, pigs weaned at 19 d of age had
      similar carcass lipid and lipid:protein accretion ratios regardless of diet
      complexity. When health status was similar, growth performance was similar
      between weaning ages but was influenced by diet complexity. Carcass lipid and
      lipid:protein deposition ratios increased when simple regimens were fed to pigs
      weaned at 9 d of age in the subsequent growing-finishing period.

PMID- 8994913
TI  - Exogenous pulses of luteinizing hormone cause persistence of the largest bovine
      ovarian follicle.
AB  - The objectives of this study were, 1) to determine whether increased frequency of
      LH pulses, independent of changes in progesterone, will cause persistence of the
      first largest ovarian follicle (LF1) during the bovine estrous cycle and 2) to
      determine whether a follicle produced in this manner will ovulate after luteal
      regression. In Exp. 1, 32 nonlactating beef cows were randomized into four
      groups. Bovine LH was given as 50 micrograms i.v. every 2 h from 0800 on d 7
      through 0800 on d 13 postestrus to cows in two groups, which in addition either
      received PGF2 alpha on d 12 and were allowed to ovulate (LHOV; Group 1) or were
      ovariectomized (LHOVX; Group 2) on d 13. Cows in Group 3 received progesterone
      via a used controlled internal drug releasing device (CIDR) on d 4 to 13, PGF2
      alpha on d 6, and ovariectomy on d 13. These cows received 1 mL of saline i.v.
      every 2 h on d 7 to 13, as did those in Group 4 (SAL), but cows in Group 4 did
      not receive any PGF2 alpha. Proportion (percentage) of LF1 maintained until d 13
      was similar in cows with CIDR (100) and on LH (88) but less in cows on SAL (36; P
      < .01). The LF1 were largest in cows with CIDR, smallest in cows on SAL, and
      intermediate in cows on LH (P < .001). During d 7 to 13, progesterone was lesser
      and estradiol was greater in peripheral plasma in cows with CIDR than in cows on
      LH or SAL (P < .001). In Experiment 2, beef heifers received 50 micrograms of bLH
      (LH; n = 5) or saline (SAL; n = 4) i.v. every 2 h from 0800 on d 7 until 12 h
      after signs of estrus were observed following PGF2 alpha on d 12. The LF1 were
      maintained by LH and 60% ovulated; all LF1 were replaced during treatment in
      heifers on SAL. The LF1 were larger in heifers on LH, but estradiol and
      progesterone did not differ between groups. In conclusion, an increased frequency
      of LH pulses during a normal luteal phase allowed LF1 to persist but did not
      increase secretion of estradiol.

PMID- 8994914
TI  - Thymic, gonadal, and endocrine relationships in gilts and boars administered
      porcine somatotropin.
AB  - We hypothesized that much of the positive effect of porcine somatotropin (pST) on
      the immune system would be offset by the pST/IGF stimulation of gonadal function
      and that there would be negative effects on thymic weight and function from
      increased androgens in males. Male and female hogs (78 boars, 90 gilts)
      representing three genetic lines (lean, obese, and crossbred meat type) received
      0, 2, or 4 mg of recombinant pST/d via implant for 42 d. Blood samples were
      collected on 0, 7, 14, 28, and 42 d of the trial for changes in pST, IGF-I, IGF
      II, thymosin beta 4, dehydroepiandrosterone/dehydroepiandrosterone sulfate
      (DHEA/DHEASO4), and testosterone concentrations. Thymic, splenic, gonadal, and
      adrenal weights were collected at slaughter (d 42). Thymic weights increased with
      dose of pST in both sexes (P < .01), but splenic weights were unaltered. Adrenal
      weights increased with dose of pST (P < .01), but gonadal weights showed no
      response to pST in either sex or any line. Overall, concentrations of pST, IGF,
      and thymosin beta 4 increased with dose of pST. Serum testosterone concentrations
      in boars declined with dose of pST in lean and obese lines, and DHEA/ DHEASO4
      declined in all lines with pST treatment. Testicular testosterone concentrations
      were not different among lines or doses of pST, indicating no stimulatory effect
      of increased pST/IGF-I on Leydig cell function. Although pST and its effects
      through increased circulating IGF are thought to be overall stimulants of growth
      and protein accretion, the actions on the tissues of the immune system
      (thymus/spleen) and steroidogenic tissues (adrenal/gonadal) can be selective.
      Increases in thymic weights and thymosin beta 4 concentrations from pST treatment
      in boars were partially due to the pST-induced decline in circulatory androgens,
      and the responses found in this in vivo model do not support pST/IGF effects
      documented in in vitro systems on Leydig cell function.

PMID- 8994915
TI  - Effects of porcine somatotropin on circulating testosterone concentrations in
      boars and mechanism of action.
AB  - Four experiments were conducted to elucidate the effects of porcine somatotropin
      (pST, growth hormone) on circulating testosterone concentrations in boars. In
      Exp. 1, jugular-cannulated obese boars were administered 4 mg recombinant (r)
      pST/d for 24 d before collection of samples at 15-min intervals over 6 h for
      measurement of pST, testosterone, and LH. Somatotropin treatment decreased plasma
      concentrations of testosterone and LH (P < .05). In Exp. 2, White composite boars
      were administered rpST with implants (4 mg/d) for 10 to 28, 16 to 28, or 22 to 28
      wk of age. Reductions in testosterone concentrations were proportional to the
      length of time rpST was administered; boars treated for 18 wk had the lowest
      testosterone concentrations. Concentrations of LH declined throughout the study
      in rpST-implanted boars but remained static in untreated, control boars. In vitro
      production of testosterone and dehydroepiandrosterone/dehydroepiandrosterone
      sulfate was unaffected by rpST treatment, and hCG stimulation of in vitro
      androgen secretion was similar in rpST and control treatments. In Exp. 3, i.v.
      injection of pituitary pST (USDA-B1; 5 micrograms/kg BW) into jugular-cannulated
      White composite and Meishan boars resulted in an acute increase in circulating LH
      followed by an increase in testosterone concentrations, which then declined to
      below preinjection levels at 6 to 7 h after pST injection. Multiple injections,
      two or four per day, of 5 micrograms pST/kg BW resulted in decreased testosterone
      concentrations in White composite boars, whereas in Meishan boars testosterone
      concentrations were unaffected (Exp. 4). Concentrations of LH were not different
      from control values in either breed, but in both breeds, four injections of pST
      per day produced lower LH concentrations than did two injections per day (P <
      .01). Depression of circulating concentrations of androgens in boars requires
      extended periods of pST treatment.

PMID- 8994916
TI  - Follicle-stimulating hormone-induced estradiol and progesterone production by
      bovine antral and mural granulosa cells cultured in vitro in a completely defined
      medium.
AB  - Functional subpopulations of granulosa cells exist in bovine follicles. This
      study was designed to compare the in vitro steroid production by cultured bovine
      antral and mural granulosa cells in response to various amounts of FSH. Antral
      and mural granulosa cells (600,000 viable cells/well) harvested from ovaries of
      PMSG-treated prepuberal calves were cultured in serum-free conditions for 4 d in
      wells containing 1 mL of defined Ham's F-12 medium, supplemented with 0, 2, or 10
      ng/mL of FSH. Culture medium was collected and replaced each day. The mean
      concentration of estradiol in culture media of bovine granulosa cells decreased
      from d 1 to d 4 (P < .001). Granulosa cell production of estradiol increased in
      antral cells following addition of 2 ng/mL FSH (P < .001) but decreased following
      addition of 10 ng/mL FSH (P < .001) as determined on d 4 by RIA and thin layer
      chromatography. In contrast, there was no response to FSH stimulation in mural
      granulosa cells. Progesterone production increased (P < .01) in a dose-dependent
      manner following stimulation with 2 or 10 ng/mL FSH and was consistently higher
      (P < .001) in antral than in mural granulosa cells. Addition of LH on d 4
      stimulated estradiol and progesterone production in antral (P < .01) but not in
      mural cells (P > .10). This suggests that FSH- and LH-induced estradiol and
      progesterone productions are considerably lower in mural than in antral bovine
      granulosa cells. This suggests that functional differences between these two cell
      compartments need to be considered in studies involving in vitro cultures of
      bovine granulosa cells.

PMID- 8994917
TI  - Effect of direct-fed fibrolytic enzymes on the digestive characteristics of a
      forage-based diet fed to beef steers.
AB  - A study was conducted to examine the method of delivery of a solution containing
      cellulases and xylanases on the digestion of a forage-based diet. Five ruminally
      cannulated beef steers (536 kg BW) were randomly assigned to a control (CON) or
      one of four enzyme treatments in a 5 x 5 Latin square experiment. Steers were fed
      a 70:30 (DM basis) grass hay:barley diet. Enzyme-treated rations contained a
      solution of fibrolytic enzymes at the rate of 1.65 mL/kg of forage DM. Enzyme
      application treatments were 1) enzyme to forage 24 h before feeding (F-24), 2)
      enzyme to forage 0 h before feeding (F-0), 3) enzyme to barley 0 h before feeding
      (B-0), and 4) enzyme infused ruminally 2 h after feeding (RI). Dry matter and NDF
      intakes were not different (P > .10) across treatments. Ruminal pH was lower and
      total VFA concentration at 16 h after-feeding was greater (P < .10) for steers
      fed enzyme treatments compared with CON. Rate of NDF disappearance was greater (P
      < .05) for enzyme-treated than for untreated grass substrate. Ruminal infusion of
      enzymes compared with F-24 and F-0 produced lower disappearance of DM at 8 and 32
      h (P < .10), NDF at 32 h (P < .10), and DM and NDF at 96 h (P < .05). Rate of DM
      disappearance of enzyme-treated grass hay was greater (P < .10) for steers fed B
      0 than for those fed F-24 and F-0 and for CON than for F-24 and F-0. Total tract
      digestibility of DM, NDF, and ADF was greater (P < .10) for F-24 and F-0 than for
      CON. Forage transit time was shorter (P < .10) for B-0 than for F-24 and F-0;
      however, all other contrasts for particulate passage did not differ (P > .10).
      Results from this study indicate that direct application of enzymes to forages is
      capable of improving forage digestion.

PMID- 8994918
TI  - Integration of regulatory signals controlling forage intake in ruminants.
AB  - Numerous factors have the potential to affect the amount of forage or pasture
      eaten by ruminant animals, including gut capacity, ability of tissues to
      metabolize nutrients, ruminal acidity, and osmolality. Much research into the
      control of food intake has tested one particular theory, often by applying
      greater degrees of stimulation than occur naturally, and is then unable to
      explain how physiological changes in that stimulus can be responsible for
      controlling intake. We have found that the effects of two or three stimuli
      (sodium acetate, sodium propionate, ruminal distension) applied together were
      additive. As to the site of this integration, receptors in the rumen wall are
      sensitive to both mechanical stimulation and acids, with transmission of impulses
      in vagal afferent fibers probably modulated by the osmolality of ruminal fluid.
      Thus, a certain degree of integration ("polymodal") is likely to have occurred at
      the level of the transceiving organ. A second level of integration is
      "polytopic." In this level stimulation of one visceral site modifies the effects
      of the same type of stimulus at another site. A third level of integration occurs
      in the central nervous system, whereby the effects of visceral stimulation might
      be balanced with signals from other stimuli (e.g., the special senses) to
      determine whether feeding should take place at any given moment. The thesis
      presented is that the central nervous system receives a nonspecific signal from
      the viscera; the animal might then learn to eat that amount of food that
      minimizes the competing discomforts of excessive abdominal visceral stimulation
      and shortage or imbalance of nutrients.

PMID- 8994919
TI  - Oxygen efficiency and the control of energy flow in animals and humans.
AB  - A new theory of feed intake regulation in ruminants has been developed as an
      alternative to the traditional view that feed consumption is limited by the
      physical and physiological constraints of the animal. Historical evidence that
      supports the traditional view has been examined. The new theory is based on the
      assumption that feed consumption has both positive and negative outcomes
      (benefits and costs). In a non-reproducing animal, benefits include yield of net
      energy for maintenance and gain. Costs are represented by the total oxygen
      consumption of the animal. The ratio between benefits and costs is calculated as
      the oxygen efficiency of feeding behavior, i.e., yield of net energy per liter of
      oxygen consumed. Voluntary energy intake corresponds to the feed consumption
      level at which oxygen efficiency is maximum. Literature examples were used to
      illustrate the predictive power of this theory. Differences in intake can be
      related to the efficiency of energy utilization, i.e., the animals' cost of
      processing feed. Current knowledge of the nature and causes of variation in
      processing costs is summarized. Secretory and absorptive processes associated
      with fiber consumption may explain why fiber can alter feed intake. Maximizing
      oxygen efficiency seems to be a unifying principle controlling other types of
      behavior such as locomotory behavior in humans. Possible physiological mechanisms
      controlling self-selected rates of locomotion are discussed in relation to the
      control of energy flow in ruminants.

PMID- 8994920
TI  - Metabolic constraints on voluntary intake in ruminants.
AB  - The weak point in all current methods or models of diet formulation is the
      prediction of intake. The major uncertainty is not in the cases in which physical
      constraints apply, but in those in which voluntary intake is limited by feedback
      from metabolic factors. Voluntary intake is, ultimately, a psychological
      phenomenon, involving the integration of many signals, and reflects the
      flexibility of biological systems evolved to cope with variability in food
      supply, composition and animal state. Conditions giving rise to regulatory
      signals may provide a framework for modeling metabolic constraints on intake. The
      empirical evidence for metabolic feedback shows that the animal's productive
      potential, which affects its ability to utilize nutrients, interacts with the
      balance of absorbed nutrients to regulate intake. The relative importance of the
      sites where nutrient imbalance occurs (microbial or host animal metabolism) is
      unclear, as is the relevant time scale (minutes or days) of response. A model of
      the effects of asynchrony of nutrient supply to ruminal microbes suggests that
      ammonia and microbial recycling and the contribution of hind-gut fermentation
      reduce the asynchrony in the balance of nutrients absorbed into the bloodstream.
      Hitherto, rather little progress has been made in mathematical modeling of the
      metabolic processes controlling intake. Models that describe the phenomenon in
      terms of global variables, such as total energy intake, protein supply, and
      protein synthetic capacity, can simulate the way constraints may operate without
      requiring or providing a deeper understanding of the metabolic processes
      involved. Models describing the flux of energy and materials down established
      metabolic pathways have the potential to explore constraints on intake, but until
      the problem of parameterizing such models can be overcome, that potential will
      remain untapped.

PMID- 8994921
TI  - Physical constraints on voluntary intake of forages by ruminants.
AB  - Voluntary dry matter intake (VDMI) of forages by ruminants may be limited by
      distention resulting from restricted flow of digesta through the gastrointestinal
      tract. An animal's capacity for fill depends on the weight and volume of digesta
      that causes distention and the flow rate of digesta from the organ in which
      distention occurs. The reticulorumen is generally regarded as the site in the
      gastrointestinal tract for which distention limits VDMI with high-fill diets,
      although evidence suggests that distention of the abomasum may also limit VDMI.
      Linear decreases in VDMI have been noted with increasing amounts of inert fill
      inserted into the reticulorumen, but results have not been consistent across
      several experiments. Reduction in VDMI depends on the extent to which intake is
      limited by fill before insertion of inert fill; hence animals with high energy
      requirements consuming relatively low-energy, high-fill diets are affected to the
      greatest extent. Because NDF generally ferments and passes from the reticulorumen
      more slowly than other dietary constituents, it has a greater filling effect over
      time than non-fibrous feed components and has been found to be the best single
      chemical predictor of VDMI. However, many other factors affect fill, including
      particle size, chewing frequency and effectiveness, particle fragility,
      indigestible NDF fraction, rate of fermentation of the potentially digestible
      NDF, and characteristics of reticular contractions. These factors are only
      partially accounted for in models that have been developed to predict VDMI.
      Increased accuracy of prediction of VDMI is expected as models continue to
      evolve.

PMID- 8994922
TI  - Modeling ruminant feed intake with protein, chemostatic, and distention
      feedbacks.
AB  - Little progress has been made in modeling intake regulation in spite of the many
      mechanisms identified as important. A model with relatively simple inputs was
      developed that included compartments for protein, soluble carbohydrate,
      digestible fiber, and very slowly digesting fiber. Distention and chemostatic
      feedbacks were combined using a previously published equation. The ratio of
      current ruminal fill to a modulating parameter for ruminal fill represented
      distention feedback. The ratio of the current flow of available energy to a
      modulating parameter for chemostatic demand represented chemostatic feedback. The
      modulating parameter for ruminal fill was based on literature reports of ruminal
      contents. Intake was adjusted based on current fill and energy flow relative to
      modulating parameters for fill and chemostatic feedback. The effect of the
      digestible organic matter (DOM) to CP ratio on DOM intake was modeled to adjust
      rates of digestion, rates of passage, and the chemostatic feedback. The model
      tested an integrated concept of intake regulation with only CP, IVDMD, and NDF as
      inputs. In spite of relatively simple inputs, the model behavior in response to
      variation in protein, digestibility, and fiber was similar to observations of
      animal responses.

PMID- 8994923
TI  - Ruminant nutrition from an environmental perspective: factors affecting whole
      farm nutrient balance.
AB  - Nutrient budgeting strategies focus primarily on recycling manure to land as
      fertilizer for crop production. Critical elements for determining environmental
      balance and accountability require knowledge of nutrients excreted, potential
      nutrient removal by plants, acceptable losses of nutrients within the manure
      management and crop production systems, and alternatives that permit export of
      nutrients off-farm, if necessary. Nutrient excretions are closely related to
      nutrient intake and can be predicted by subtracting predicted nutrients in food
      animal products exported from the farm from total nutrients consumed.
      Intensifying crop production with double- or triple-cropping often is necessary
      for high-density food animal production units to use manure without being forced
      to export manure or fertilizer coproducts to other farms. Most manures are P-rich
      relative to N largely because of 1) relatively large losses of volatilized NH3,
      most of it converted from urea in urine, 2) denitrification losses in soil under
      wet, anaerobic conditions, and 3) ability of many crops to luxury-consume much
      more N than P. Most soils bind P effectively and P usually is permitted to
      accumulate, allowing for budgets to be based on N. However, P budgeting may be
      required in regions where surface runoff of P contributes to algae growth and
      eutrophication of surface waters or where soil P increases to levels of concern.
      Research is needed to determine whether dietary P allowances can be lowered
      without detriment to animal production or health in order to lower P intake and
      improve N:P ratios in manure relative to fertilization needs.

PMID- 8994924
TI  - Impact of environmental regulations on cattle production.
AB  - A greater focus of legislative mandates is directed toward nonpoint sources of
      pollution. This article focuses on environmental regulations and their impact on
      cattle production. Key legislation will be reviewed to stress how variations in
      the type of law, degree of impact, enforcement mechanism, and time line for
      compliance affect the ability for research to be designed and accomplished in a
      desired time frame and to yield data on which imposed management practices should
      be based. Science-based regulations are desired to maximize beneficial impacts of
      management practices; however, many regulations are developed and management
      practices are imposed prior to research to minimize liability of the regulatory
      agency in case natural resources are degraded in the absence of management
      practices. The technology adoption process will be reviewed. Documented impact of
      imposed management practices (technology adoption) will be presented. Of
      particular interest is the importance of documenting the economic and resource
      impacts of regulations on livestock operators. Types of research needed prior to
      implementing management practices will be reviewed. Local involvement can
      increase the adoption rate of practices and technologies.

PMID- 8994925
TI  - A review on environmental impacts of nutritional strategies in ruminants.
AB  - Primary (plant), secondary (animal), and tertiary (human) biological systems are
      driven by energy, either fossil or renewable energy in biomass. Their ratio
      shifts from about 10:90 in primary, via 25:75 in secondary, to 90:10 in tertiary
      systems. Energy input in ruminant production is mainly as plants and plant parts
      from primary production, and the amount needed per unit product (milk, meat)
      primarily depends on its digestibility. This is high in young, leafy, whole
      plants, in roots and tubers, and in reproductive organs (whole seeds) or organ
      parts (by-products) of mature plants. Use of fossil energy per kilogram of DM for
      primary production ranges from 1 to 3 MJ in forage to over 8 MJ in concentrate
      feeds, whereas input per kilogram of milk is 1 to 10 MJ. Biomass energy used in
      ruminant production contains nitrogen (N), phosphorus (P), and potassium (K), but
      in a ratio rarely balanced to the animals requirements. In secondary systems,
      energy is partitioned between foods of animal origin and waste. The latter
      contains OM, N, P, K, and gases (CO2, CH4), which may cause environmental
      problems. Losses per kilograms of milk vary and are 10 to 45 g for N, 0 to 3 g
      for P, and 2 to 20 g for K. Environmental impacts of animal production can be
      reduced by varying the use of inorganic fertilizer and changing the forage to
      concentrate ratio. Digestibilities can be improved by proper harvest management.
      Level and ratio of dietary N, P, and K can be adjusted to requirements by
      selecting proper ingredients, reducing their loss in waste. Limited scope exists
      to reduce losses in respiration and fermentation gases.

PMID- 8994927
TI  - Calling all psychiatric rehabilitation practitioners: are you registered?

PMID- 8994926
TI  - Getting the story straight and passing it along. New thoughts on promoting
      collaborative partnerships with consumers, survivors, and family members.

PMID- 8994928
TI  - Sticks and stones--and depression--may break bones.

PMID- 8994929
TI  - Education program targets anxiety disorders.

PMID- 8994930
TI  - Who's the patient here? Inpatient psychiatric rehabilitation in a state hospital
      setting.
AB  - 1. The primary focus of psychiatric rehabilitation is on improving the
      competencies of persons with psychiatric disabilities. 2. Both patients and staff
      must change their ideas about themselves and each other before the work of
      rehabilitation could move forward. 3. Institutional rigidity works against
      psychiatric rehabilitation, with its value on individual growth and self
      sufficiency.

PMID- 8994931
TI  - An innovation in psychiatric rehabilitation programming. Supported education.
AB  - 1. In the rehabilitation and recovery process, every person deserves a carefully
      tailored plan to meet individual needs. 2. The best nursing practice begins with
      a link between the nursing process and creative critical thinking skills,
      focusing on connecting with the consumer to build a strong rehabilitation
      oriented relationship. 3. The rehabilitation process is enhanced when the nurse
      uses principles of psychiatric rehabilitation and has knowledge about local and
      state rehabilitation options available-including supported education.

PMID- 8994932
TI  - Mental illness and the Americans with Disabilities Act. Understanding the
      fundamentals.
AB  - 1. With an increasing emphasis on psychiatric rehabilitation, psychiatric nurses
      must understand the Americans with Disabilities Act (ADA) and the application of
      the legislation to the mentally disabled. 2. The ADA applies to all who are
      disabled physically or as the result of emotional or mental illness, and is
      intended to promote equality of opportunity, full participation in society, and
      economic self-sufficiency. 3. Because much of the ADA was drafted from the
      perspective of the physically disabled, it sometimes is a challenge to apply the
      regulations to people with mental illness.

PMID- 8994933
TI  - The clubhouse model as exemplar. Merging psychiatric nursing and psychosocial
      rehabilitation.
AB  - 1. Psychiatric nurses have much to learn from and offer to the field of
      psychosocial rehabilitation and the psychiatric rehabilitation approach. 2.
      Psychiatric rehabilitation hopes to increase the functioning of persons with
      psychiatric disabilities so they can be successful in their environments with the
      least amount of ongoing professional intervention. 3. The hope of recovery, and
      of living, working, and loving in a community, is a significant advance from
      previous notions of how to care for persons with mental illness.

PMID- 8994934
TI  - Exploring the field. Strengthening psychiatric rehabilitation nursing practice
      with new information and ideas.
AB  - 1. Nurses working in traditional psychiatric inpatient settings are becoming more
      aware of rehabilitation as it applies to people who experience long term mental
      illness. 2. With the advent of managed care models, a large percentage of nursing
      staff will shift from traditional inpatient care to work with consumer-survivors
      in rehabilitation-oriented, community-based settings. 3. As nurses increase
      involvement in assessing and providing psychiatric rehabilitation interventions,
      they will need information sources focused on psychiatric rehabilitation for
      persons with serious mental illness.

PMID- 8994935
TI  - Effects of brain injury on college academic performance.
AB  - Brain injury, a leading cause of mortality, morbidity and disability in the
      United States, has serious consequences and substantial costs. Although previous
      studies have assessed a variety of outcomes subsequent to brain injury,
      documentation of performance prior to brain injury using a case-control approach
      has not been included; preinjury performance differences may confound the
      estimate of the effects of brain injury on performance. The primary objective of
      this study was to compare academic performance before and after brain injury in a
      population of university undergraduate students to determine the extent to which
      the academic career of the brain-injured person was altered from what would have
      been expected in the absence of such an injury. Cases included all undergraduate
      students in a major university, between the ages of 17 and 27, who incurred a
      brain injury requiring hospitalization between 1980 and 1984 (n = 99). Two
      comparison groups were used to determine whether changes in academic performance
      were specifically related to brain injuries or injuries in general: (1) injured
      controls, i.e. 121 students between the ages of 17 and 27 years, hospitalized for
      injuries other than to the central nervous system, and (2) uninjured academic
      controls, i.e. 198 students with out injuries requiring hospitalization during
      the study period, matched 2:1 to the brain-injured students by age, gender, and
      completed course credits categorized as < 90, > or = 90. Although there were no
      differences when the total groups, including both males and females, were
      compared, there was a significant pre- to postinjury decrease in the grade point
      average for female cases when compared to their uninjured academic controls (p <
      0.02). This difference was related to the effects of brain injury, and not to the
      effects of injury in general. No such difference was observed for the males.
      There were also no differences when the total groups, including males and
      females, were compared relevant to return to school. However, a significantly
      higher proportion of the female cases, compared with their uninjured academic
      controls, did not return to school after their injury; similar findings were
      identified for the injured controls as well. Thus, these differences were not
      specific to brain injury but rather to injury in general. In spite of this
      observation, the difference between female cases who returned and those who did
      not return was associated with neurological deficits, especially upper left limb
      motor deficits, as the time of hospital discharge. The findings from this effort
      are suggestive of gender differences in the consequences of brain injury and
      serve as a basis for further studies to evaluate the magnitude of this problem.

PMID- 8994936
TI  - A hospital-based and a population-based stroke registry yield different results:
      the experience in Dijon, France.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to demonstrate the different
      results obtained from a population-based and a hospital-based stroke study in the
      same city. METHODS: Between January 1 and December 31, 1993, we collected
      information on all of the first strokes in the population of the city of Dijon,
      in conjunction with the Dijon Stroke Registry, collecting the first-ever strokes
      from patients living in Dijon as well as on all the first strokes in residents
      and nonresidents of Dijon who were treated at Dijon University Hospital.
      Demographic details, medical history, vascular risk factors, stroke subtype, as
      diagnosed by CT scan, and mortality rates were compared between the strokes
      observed in the population of the city of Dijon among residents as well as
      nonresidents in Dijon who were treated at Dijon University Hospital. RESULTS: We
      collected information on 210 strokes observed in the population of Dijon city,
      171 Dijon residents and 395 non-Dijon city residents hospitalized at the
      University Hospital of Dijon. These three groups were quite different. The
      residents of Dijon treated for stroke at the University Hospital were younger and
      their incidence of cerebral hemorrhage, cardiac arrhythmia, ischemic heart
      disease and case fatality rate were higher than those from the Dijon Stroke
      Registry. CONCLUSIONS: Type of stroke data bank is very important in order to
      describe cerebrovascular disease. Hospital-based studies tend to include more
      severe strokes, those occurring in a younger population, and those having a
      higher mortality. Population-based studies, on the other hand, give a somewhat
      different picture of stroke.

PMID- 8994937
TI  - Prognosis of childhood epilepsy: a community-based study in Copparo, Italy.
AB  - We performed a community-based study among children and adolescents with
      idiopathic and cryptogenic epilepsy and onset of the seizures between 0 and 19
      years of age on the prognosis of being seizure-free. The study population was
      recruited during a descriptive investigation in the Local Health Service of
      Copparo (USL 34), Ferrara, Northern Italy. We included 111 patients (61 males and
      50 females). The average length of follow-up was 18.8 years (ranging from 7 to 24
      years). The cumulative probability of being in remission was 81.2% at 15 years
      after onset and the estimated percentage of patients in remission without therapy
      was 56% for the same time period. At 15 years after the onset of epilepsy,
      approximately 20% of patients continued to have seizures; nearly 25% continued to
      take antiepileptic drugs but had been free of seizures for at least 5 years;
      nearly 56% had been without seizures and free of medication for at least 5 years.
      Seizure type, gender, age at onset of the illness, epileptic abnormalities on
      EEG, family history of convulsive disorders, number and frequency of seizures
      prior to the start of treatment were found not to be helpful as prognostic
      factors. This community study, carried out on patients without the well known
      factors that adversely affect prognosis, confirms that the prospect of seizure
      control and for withdrawal of therapy is (generally) good.

PMID- 8994938
TI  - Cognitive predictors of dementia in elderly community residents.
AB  - Detection of subjects with a high risk of developing dementia is a major goal of
      epidemiological research. Among the potential predictors, minor cognitive
      impairments detected by psychometric methods could be important precursors. A
      total of 2,726 elderly nondemented subjects, aged 65 and over, randomly selected
      from the general population of Gironde (south-western France) were followed up
      for 3 years. During this time, 84 developed an incident dementia, diagnosed as
      Alzheimer's disease (AD) in 59. The relationships between cognitive performance
      (Mini Mental State Examination, Benton Visual Retention Test and Isaacs Set Test)
      measured at the baseline screening of the cohort and the risk of dementia or AD
      were studied with a discrete Cox proportional hazard model. After adjustment for
      age and educational level, the three test scores remained strongly related to the
      risk of dementia or AD. Psychometric performance can be used to screen subjects
      at risk of developing dementia or AD and allow pharmacological intervention at an
      early stage.

PMID- 8994939
TI  - Stroke in Kuwait: a three-year prospective study.
AB  - To study the pattern of stroke in Kuwait, prospective data were collected from
      all patients admitted with first-ever stroke to our hospital over 3 years: 1989,
      1992 and 1993. The primary-care registry over the same period was examined to
      ascertain that all cases of stroke seen by the primary-care doctors were referred
      to a hospital. Death certificates issued for people who died outside the hospital
      were also examined. The study included: clinical evaluation, computed tomography,
      electrocardiography, blood laboratories, serum chemistry and other investigations
      as required. The overall annual crude incidence rate was 27.6/100,000 population.
      The age-adjusted annual crude incidence rate was 145.6/100,000 population. No
      seasonal variation in the stroke incidence was observed in our study. Carotid
      territory large infarction represented 46.5% of all strokes followed by
      intracerebral haemorrhage in 19.9%, lacunar infarction in 17%, basilar infarction
      in 8.3% and subarachnoid haemorrhage in 1.7%. The overall case fatality rate was
      10%. Mortality increased with age and when loss of consciousness was present. The
      study demonstrated that stroke incidence in Kuwait is very low due to the young
      average age of the Kuwaiti population.

PMID- 8994940
TI  - Sociodemographic factors and primary headache syndromes in a Saudi community.
AB  - BACKGROUND AND PURPOSE: There is increasing evidence that the pathophysiologic
      mechanisms are different between migraine and tension-type headache. The aim of
      the study was to determine possible sociodemographic differences in Saudi Arabia
      subjects with headache. METHODOLOGY: A community-based door-to-door survey with
      identification of headache cases based on IHS criteria. A comparison of
      sociodemographic variables was made between subjects with migraine and tension
      type headache. RESULTS: Headache prevalence was 8% (95% CI = 7.3-8.7%) with a
      preponderance of tension-type headache (39%). Females were more often affected
      than males (ratio 2:1). Migraine subjects were more often in the professional
      occupational group compared with tension-type headache (p < 0.05). CONCLUSION:
      Headache prevalence in the community was low. Subjects with migraine and tension
      type headache were similar with respect to many demographic variables.
      Occupational association needs verification in further studies.

PMID- 8994941
TI  - The importance and limitations of prospective randomized studies for new,
      evolving surgical procedures: lessons from the dynamic cardiomyoplasty trial.

PMID- 8994942
TI  - Analysis of high frequency QRS potential during exercise testing in patients with
      coronary artery disease and in healthy subjects.
AB  - High resolution ECG waveforms from leads V3, V4, V5, and V6 were analyzed in two
      groups of male subjects before, during, and following treadmill exercise testing.
      Group A included 32 coronary artery disease (CAD) patients, with
      arteriographically proven > 75% obstruction of at least two main coronary
      arteries, and group B included 30 healthy subjects, without history or symptoms
      of CAD. Signal averaging and filtering techniques were used in order to enhance
      the signal-to-noise ratio of the recorded ECG. The averaged QRS waveforms were
      filtered between 150 and 250 Hz. QRS complexes of the four leads were combined to
      form a "precordial average complex" (PAC). The PAC signals were examined for each
      subject at different stages of the exercise test and two parameters were
      computed: the root mean square (RMS) voltage; and the peak amplitude. The values
      of RMS and peak amplitudes measured at each stage of the exercise test were
      normalized to the values at rest. Normalized RMS (NRMS) values at peak exercise,
      immediately after peak exercise, and during the recovery phase were found to be
      higher for the healthy subjects than for the CAD group (1.17 +/- 0.31 vs 0.94 +/-
      0.26, P < 0.008 at peak exercise, 1.13 +/- 0.24 vs 0.84 +/- 0.19, P < 0.001 after
      peak exercise, 1.08 +/- 0.22 vs 0.94 +/- 0.17, P < 0.007 during recovery). Cut
      off NRMS value of one had a sensitivity of 81.3% and a specificity of 70.0% in
      differentiating CAD patients from healthy subjects in the examined groups.
      Normalized peak amplitude (NAMP) values exhibited similar behavior, with higher
      values for the healthy subjects than for the CAD group (1.23 +/- 0.48 vs 0.94 +/-
      0.36, P < 0.03 at peak exercise, 1.20 +/- 0.34 vs 0.83 +/- 0.28, P < 0.001 after
      peak exercise, 1.10 +/- 0.29 vs 0.94 +/- 0.23, P < 0.02 during recovery).
      Specificity of 73.3% and sensitivity of 71.8% were found using a postpeak NAMP
      cut-off value of 1. In conclusion, the present study shows that using high
      frequency ECG may contribute to identifying patients with CAD. Further studies in
      larger groups of patients are required to better define the true predictive value
      of the method described for the diagnosis of CAD.

PMID- 8994943
TI  - Dual level sensing significantly improves automatic threshold control for R wave
      sensing in implantable defibrillators. The Angeion Corporation.
AB  - ICDs must sense R waves over a range of amplitudes without sensing P or T waves.
      Automatic threshold control (ATC) is an accepted sensing method for that task.
      ATC sensing levels are from 25%-75% of the electrogram (EGM) peak, decreasing
      with an exponential decay. A high sensing level for a time after peak detection
      may better allow ATC to pass over a T wave, while a lower sensing level
      thereafter may better allow ATC to sense the next R wave. An ATC was designed
      with two sensing levels and time constants (tau), using a 58% level (tau = 1.75
      s) for 325 ms after peak detection switching to 33% (tau = 1.1 s) thereafter, and
      was compared to a single level ATC (sensing level = 50%, tau = 1.4 s). The two
      ATC circuits were tested with 22 arrhythmia EGMs to determine sensitivity and
      specificity rates at +/-1-, 2-, 5-, 10-, and 20-mV amplitudes. It was confirmed
      that a dual level ATC significantly improves the sensitivity rate without
      degrading the high specificity rate of a standard sensing circuit.

PMID- 8994944
TI  - A new contact probe for intraoperative laser ablation.
AB  - Several clinical factors decrease the accuracy of intraoperative laser ablation.
      The distance to the target, the irradiation angle, and the media are reported
      among these factors. We developed a new laser probe to resolve these problems.
      This probe has a hollow conical tube with a tip covered by a thin film. Zero
      degree centigrade saline was fed into this probe. Results from using the new
      probe were compared with those from the conventional noncontact irradiation
      method with cooling by sprinkled cooling water. In beating canine hearts,
      ventricles were irradiated with neodymium:yttrium aluminum garnet (Nd:YAG) lasers
      at 50-200 J/mm2. There was no difference in the mean volume of irradiated tissue
      between the new and the noncontact method. However, the distribution of volume
      values in the new method was smaller than that in the noncontact method (P <
      0.05). In conclusion, results obtained indicate that this new probe could perform
      more accurate intraoperative ablation than the conventional method. Problems of
      stabilizing the distance to the target, the irradiation angle, and the media were
      resolved.

PMID- 8994945
TI  - An implantable intracardiac accelerometer for monitoring myocardial
      contractility. The Multicenter PEA Study Group.
AB  - As the myocardium contracts isometrically, it generates vibrations that are
      transmitted throughout the heart. These vibrations can be measured with an
      implantable microaccelerometer located inside the tip of an otherwise
      conventional unipolar pacing lead. These vibrations are, in their audible
      component, responsible for the first heart sound. The aim of this study was to
      evaluate, in man, the clinical feasibility and reliability of intracavity
      sampling of Peak Endocardial Acceleration (PEA) of the first heart sound
      vibrations using an implantable tip mounted accelerometer. We used a
      unidirectional accelerometer located inside the stimulating tip of a standard
      unipolar pacing lead: the sensor has a frequency response of DC to 1 kHz and a
      sensitivity of 5 mV/G (G = 9.81 m/s-2). The lead was connected to an external
      signal amplifier with a frequency range of 0.05-1,000 Hz and to a peak-to-peak
      detector synchronized with the endocardial R wave scanning the isovolumetric
      contraction phase. Following standard electrophysiological studies, sensor
      equipped leads were temporarily inserted in the RV of 15 patients (68 +/- 15
      years), with normal regional and global ventricular function, to record PEA at
      rest, during AAI pacing, during VVI pacing, and during dobutamine infusion (up to
      20 micrograms/kg per min). PEA at baseline was 1.1 G +/- 0.5 (heart rate = 75 +/-
      14 beats/min) and increased to 1.3 G +/- 0.9 (P = NS vs baseline) during AAI
      pacing (heart rate = 140 beats/min) and to 1.4 G +/- 0.5 (P = NS vs baseline)
      during VVI pacing (heart rate = 140 beats/min). Dobutamine infusion increased PEA
      to 3.7 G +/- 1.1 (P < 0.001 vs baseline), with a heart rate of 121 +/- 13
      beats/min. In a subset of three patients, simultaneous hemodynamic RV monitoring
      was performed to obtain RV dP/dtmax, whose changes during dobutamine and pacing
      were linearly related to changes in PEA (r = 0.9; P < 0.001). In conclusion, the
      PEA recording can be consistently and safely obtained with an implantable device.
      Pharmacological inotropic stimulation, but not pacing induced chronotropic
      stimulation, increases PEA amplitude, in keeping with experimental studies,
      suggesting that PEA is an index of myocardial contractility. Acute variations in
      PEA are closely paralleled by changes in RV dP/dtmax, but are mainly determined
      by LV events. The clinical applicability of the method using RV endocardial leads
      and an implantable device offers potential for diagnostic applications in the
      long-term monitoring of myocardial function in man.

PMID- 8994946
TI  - Initial single-center experience with an advanced third-generation
      investigational defibrillator.
AB  - The CPI PRxII is a recently approved, multitiered implantable cardioverter
      defibrillator (ICD) that delivers high and low energy biphasic shocks,
      antitachycardia (ATP) and bradycardia pacing, and stores 2.5 minutes of
      electrograms from the widely spaced shocking electrodes. The PRxII was implanted
      in 58 patients at Yale-New Haven Hospital between December 1993 and January 1995.
      At implant, mean biphasic defibrillation threshold (DFT) in patients with testing
      to failure was 10 J (1-20). All 36 patients who were candidates for a new
      transvenous system underwent successful nonthoracotomy implantation. Based on
      noninvasive predischarge EPS results, 30 patients had > or = 1 VT zone: 21
      patients had ATP, 9 others had first shock < or = 5 J. During follow-up, 13
      patients had been treated for 379 events (range, 1-127). Of 340 events in a zone
      with ATP, 97% responded to ATP, 3% required shock. First programmed shock
      converted all events in a VF zone. Details, including RR intervals, were
      available for all events in 15 of 17 patients receiving appropriate or
      inappropriate therapy or diverted shocks. One hundred eleven of 148 available
      electrograms confirmed VT by morphology, rate, and/or presence of AV
      dissociation. In nine patients, electrogram data altered therapy through
      diagnosis of inappropriate or diverted therapy, guidance of detection
      enhancements, or diagnosis of previously unrecognized VTs. We conclude the PRxII
      achieves low DFTs that obviate the need for thoracotomy and effectively treats
      ventricular arrhythmias with ATP and shock, with programming guided by
      noninvasive electrophysiology. Multiple stored electrograms from widely spaced
      shocking electrodes greatly enhance diagnostic capabilities, facilitating
      effective treatment.

PMID- 8994947
TI  - Comparison of a unipolar defibrillation system with a dual lead system using an
      enlarged defibrillation anode.
AB  - The unipolar system for transvenous defibrillation, consisting of a single right
      ventricular lead as the cathode and the device shell as anode, has been shown to
      combine low defibrillation thresholds (DFTs) and simple implantation techniques.
      We compared the defibrillation efficacy of this system with the defibrillation
      efficacy of a dual lead system with a 12-cm long defibrillation anode placed in
      the left subclavian vein. The data of 38 consecutive patients were
      retrospectively analyzed. The implantation of an active can system was attempted
      in 20 patients (group 1), and of the dual lead system in 18 patients (group 2).
      Both groups had comparable demographic data, cardiac disease, ventricular
      function, or clinical arrhythmia. The criterion for successful implantation was a
      DFT of < or = 24 J. This criterion was met in all 18 patients of group 2. The
      active can system could not be inserted in 3 of the 20 group 1 patients because
      of a DFT > 24 J. In these patients, the implantation of one (n = 2) or two (n =
      1) additional transvenous leads was necessary to achieve a DFT < or = 24 J. The
      DFTs of the 17 successfully implanted group 1 patients were not significantly
      different from the 18 patients in group 2 (12.3 +/- 5.7 J vs 10.8 +/- 4.8 J). The
      defibrillation impedance was similar in both groups (50.1 +/- 6.1 omega vs 48.9
      +/- 5.2 omega). In group 1, both operation duration (66.8 +/- 17 min vs 80.8 +/-
      11 min; P < 0.05) and fluoroscopy time (3.3 +/- 2.1 min vs 5.7 +/- 2.9 min; P <
      0.05) were significantly shorter. Thus, the active can system allows reliable
      transvenous defibrillation and a marked reduction of operation duration and
      fluoroscopy time. The dual lead system, with an increased surface area
      defibrillation anode, seems to be a promising alternative for active can
      failures.

PMID- 8994948
TI  - Transtelephone monitoring for pacemaker follow-up 1981-1994.
AB  - Transtelephone monitoring (TTM) is capable of detecting pacemaker pulse generator
      malfunction, battery depletion, and lead failure. The accuracy of TTM was
      analyzed by a review of Montefiore Medical Center records between October 1981
      and March 1994. Each group of transmissions from a single patient, starting with
      implant and ending with a pacemaker operation, was defined as a closed cycle
      (CLOSE), if undergoing continuing follow-up at the time of analysis, as a
      continuing cycle (CONT), and if a cycle had ended with death or loss to follow
      up, an open cycle (OPEN). TTM records of 2,632 patients were analyzed, providing
      3,291 cycles. There were 731 CONT, 433 CLOSE, and 2,127 OPEN cycles; 331
      procedures were indicated by TTM, of which 279 were impending depletion, 30
      sudden depletion, and 22 lead malfunctions. Of the 102 procedures not indicated
      by TTM, 85 were for nonurgent reasons (recall: 41; DDD upgrade: 16; patient/MD
      request: 28) and 17 for urgent reasons. In patients followed by TTM who had a
      lead problem, 22 were detected by TTM before clinical manifestations and 16 were
      not. There were no cases in which TTM follow-up did not detect battery depletion.
      The total number of TTM contacts, available for 3,094 cycles, was 88,654 (range,
      1-163, median 19), of which 0.4% yielded a procedure. During the same period, 75%
      of all secondary interventions during the first 2 years occurred during the first
      2 months after implant because of lead malfunction, with a subsequent SI rate of
      0.005 per month for the third through the twenty-fourth months.

PMID- 8994949
TI  - Programmable polarity: effects on pacing and sensing of bipolar steroid-eluting
      leads.
AB  - Presently available bipolar pacemakers connected to bipolar leads allow the
      programming of polarity to either bipolar or unipolar configuration. The bipolar
      configuration improves sensing because of its lack of oversensing. In respect to
      the pacing impulse, it may be beneficial to program the bipolar to unipolar
      configuration, because the unipolar pacing configuration seems to lead to lower
      pacing thresholds. The aim of the study was to investigate the effects of the two
      configurations on pacing and sensing in 11 patients with a new ventricular
      steroid-eluting lead (Encor Dec 033-301, Telectronics Inc.) connected to the same
      types of VVI(R) pacemakers. Follow-up was 12 months after implantation. Pacing
      was assessed by pulse duration thresholds at 0.8- 1.6-, and 2.5-V pulse amplitude
      and by pacing impedance. Parameters for sensing included sensing thresholds, R
      wave amplitudes, and amplitude of intrinsic deflection. Pulse duration thresholds
      were similar for the two configurations. At implantation, pacing impedance was
      significantly higher with bipolar (672 +/- 60 omega) than with unipolar pacing
      configuration (626 +/- 82 omega, P < 0.005). The difference lasted until 1 month
      after implantation (bipolar: 670 +/- 49 omega; unipolar: 63053 omega, P < 0.01).
      No significant differences were detected after 3 (bipolar: 683 +/- 63 omega;
      unipolar: 662 +/- 70 omega) and 12 months (bipolar: 658 +/- 64 omega; unipolar:
      660 +/- 63 omega) between the 2 configurations. Although intrinsic deflections of
      ventricular electrograms were different, mean R wave amplitudes were similar in
      unipolar and bipolar configuration. Pacing and sensing characteristics of
      unipolar and bipolar configuration were similar for the studied bipolar pacing
      lead. Pacing impedance was initially higher for bipolar than for unipolar
      configuration and equilibrated within 3 months after implantation.

PMID- 8994950
TI  - Comparative reproducibility of defibrillation threshold and upper limit of
      vulnerability.
AB  - The upper limit of vulnerability (ULV) is the strength at or above which VF is
      not induced when a stimulus is delivered during the vulnerable phase of the
      cardiac cycle. Previous studies have demonstrated a statistically significant
      correlation between the ULV and the defibrillation threshold (DFT) in groups of
      patients. However, the correlation between ULV and DFT may not be close in
      individual patients. This imperfect correlation may be due to physiological
      factors or to limitations of the measurement methods. The reproducibility of
      either DFT or ULV has not been studied critically. The purpose of this study was
      to compare the reproducibility of clinically applicable methods for determination
      of DFT and ULV. We prospectively studied 25 patients with a transvenous
      implantable cardioverter defibrillator (Medtronic 7219D) at postoperative
      electrophysiological study. DFT was defined as the lowest energy that
      defibrillated after 10 seconds of VF. The ULV was defined as the lowest energy
      that did not induce VF with three shocks at 0, 20, and 40 ms before the peak of
      the T wave in ventricular paced rhythm at a cycle length of 500 ms. Both the DFT
      and the ULV were determined twice for biphasic pulses using a three-step,
      midpoint protocol. There was no significant difference between the two
      determinations of DFT (10.1 +/- 5.9 J vs 10.4 +/- 5.8 J), the two determinations
      of ULV (13.4 +/- 6.8 J vs 13.8 +/- 6.6) or the DFT-ULV Pearson correlation
      coefficients for each determination (0.84, P < 0.001 vs 0.75, P < 0.001). To
      analyze reproducibility, Lin concordance coefficients for second determination
      versus first determination were constructed for both ULV and DFT. This
      coefficient is similar to the Pearson correlation coefficient, but measures
      closeness to the line of identity rather than the line of regression. The Lin
      concordance coefficient for ULV was higher than that for DFT (0.93, 95% CI 0.85
      0.97 vs 0.64, 95% CI 0.33-0.82; P < 0.01). For paired comparison of
      defibrillation efficacy under different experimental conditions, the sample sizes
      required to detect differences of 2 J, 3 J, and 4 J (80% power, P < 0.05) were
      52, 24, and 15 for DFT versus 15, 8, and 6 for ULV. We conclude that a simple,
      clinically applicable method for determination of ULV is more reproducible than
      the single point DFT. Measured correlations between the ULV and single point are
      limited by the reproducibility of the DFT measurement.

PMID- 8994951
TI  - Heart rate variability after cardiac transplantation in humans.
AB  - The reappearance of cardiac innervation after cardiac transplantation remains a
      matter of debate. We evaluated the ability of heart rate variability (HRV)
      analysis to detect the extent and time course of functional cardiac allograft
      reinnervation. Time- and frequency-domain analysis of heart rate was performed on
      Holter recordings of 120 heart transplant and four heart-lung transplant
      recipients. A high frequency (HF) component was clearly distinguished on visual
      inspection of power spectral density in 42 patients. In eight patients an HF
      component of normal magnitude was detected. The other 34 patients in this group,
      including all four heart-lung transplants, presented with a very small HF
      component. The other 82 patients showed a flat spectrum. The group with an HF
      component of normal amplitude was significantly different, compared to the other
      groups, for all HRV parameters. Serial plotting of HRV parameters of the patients
      with an HF component of normal amplitude against time posttransplant, revealed,
      from 12 months onwards, a progressive increase of parameters denoting HF
      variability. In five heart transplant patients with acute allograft rejection,
      the use of HRV analysis for rejection monitoring was unsuccessful. These results
      suggest that, inasmuch as the HF component of HRV is caused by parasympathetic
      cardiac innervation, the HF component of normal amplitude, observed in only a
      minority of cardiac transplant recipients (6%), is a marker for parasympathetic
      reinnervation. The evolution over time of this HF component is compatible with a
      biological phenomenon as gradual parasympathetic reinnervation of the sinus node.

PMID- 8994953
TI  - Web sites in cardiology.

PMID- 8994952
TI  - Idiopathic right ventricular outflow tract tachycardia: a clinical approach.
AB  - Right ventricular outflow tract (RVOT) tachycardia is the most common form of
      idiopathic ventricular tachycardia (VT). Phenotypically, RVOT tachycardia
      segregates into two predominant forms, one characterized by repetitive
      monomorphic nonsustained VT and the other by paroxysmal exercise induced
      sustained VT. There is an increasing body of evidence to support the concept that
      both forms of tachycardia reflect disparate clinical manifestations of an
      identical cellular mechanism (i.e., cAMP-mediated triggered activity), which is
      identified clinically by the tachycardia's sensitivity to adenosine. The clinical
      characteristics, natural history, and approaches to therapy of RVOT tachycardia
      are delineated herein.

PMID- 8994954
TI  - United States health policy issues in 1997: a return to the Medicare wars and
      managing managed care.

PMID- 8994956
TI  - Late endocardial pacing lead body migration compromising Fontan physiology.
AB  - Migration of intracardiac transvenous pacing leads may occur. There is a known
      risk of intrapulmonary ventricular pacing lead migration in patients with
      endocardial lead systems. In the current report we present the late
      intrapulmonary migration of an endocardial atrial pacing lead body. The patient
      had undergone antitachycardia pacemaker placement to control recurrent atrial
      tachyarrhythmias following the Fontan procedure. Although the lead electrode
      remained in place and continued to pace, the lead body migrated, causing severe
      obstruction to blood flow. This resulted in severe cardiac decompensation, which
      was ultimately ameliorated by lead repositioning.

PMID- 8994955
TI  - Catheter ablation of idiopathic left ventricular tachycardia associated with a
      false tendon.

PMID- 8994957
TI  - Symptomatic pericardial disease associated with patch electrodes of the automatic
      implantable cardioverter defibrillator: an underestimated complication?
AB  - Constrictive pericarditis can be associated with ICD patch electrodes. During a
      mean follow-up of 24 months, in a population of 35 patients who received ICDs
      with a patch electrodes configuration, we identified three patients with clinical
      and hemodynamic signs compatible with this event. Patient 1, a 35-year-old male,
      underwent implantation of an ICD because of a primary electrical disease
      complicated by cardiac arrest. Fourteen months later he complained of exertional
      dyspnea without any signs of heart failure. Right heart catheterization showed
      high filling pressures and diastolic dip and plateau in pressure curves.
      Thoracotomy and pericardial exploration were performed. Three months after
      removal of the patches and insertion of an endocardial lead system, the patient
      had normal respiration. Patients 2 and 3, who suffered from coronary heart
      disease without heart failure, exhibited a hemodynamic profile suggestive of
      constrictive pericarditis: in one patient, 10 months after ICD implantation,
      associated with right heart failure; and in the other, 18 months after ICD
      implantation with left heart failure. Patch electrodes were removed in these two
      patients and replaced by endocardial lead electrodes with subsequent clinical
      improvement. It is concluded that constrictive pericarditis related to epicardial
      patch is not an uncommon occurrence during ICD therapy and should be considered
      in patients who show clinical signs of cardiac decompensation.

PMID- 8994958
TI  - Effect of dual chamber atrioventricular sequential pacing on coronary flow
      velocity in a patient with hypertrophic obstructive cardiomyopathy.
AB  - Effects of dual chamber AV sequential pacing on coronary flow velocity,
      especially systolic reversal flow, were tested in a patient with hypertrophic
      obstructive cardiomyopathy. AV sequential pacing with shorter AV delays reduced
      the systolic reversal flow in the coronary artery, and improved the pressure
      gradient of the left ventricular outflow tract.

PMID- 8994959
TI  - Aspergillus fumigatus infection of an automatic internal cardiac defibrillator.
AB  - We report a patient without immune compromise with infection of an automatic
      internal cardiac defibrillator patch due to Aspergillus fumigatus presenting 8
      years after implantation. The mechanism of infection was unknown, but symptoms
      began 1 month after laser uvulopalatopharyngoplasty was performed for sleep
      apnea. The patches were surgically removed and the patient was treated
      sequentially with amphotericin B and itraconazole. He remains without evidence of
      infection 12 months after the completion of therapy.

PMID- 8994960
TI  - Pacemaker Twiddler's syndrome.
AB  - Twiddler's syndrome may result from pulse generator manipulation or from
      spontaneous rotation due to movement around an inadequately secured electrode. In
      this case, the electrode became coiled in the right ventricular outflow tract.

PMID- 8994961
TI  - Correct the QT interval correctly.

PMID- 8994962
TI  - No output or runaway?

PMID- 8994963
TI  - Emergency VVI pacing.

PMID- 8994964
TI  - Precluding uracil from DNA.
AB  - Two enzymes, dUTP pyrophosphatase and uracil-DNA glycosylase, prevent the
      misincorporation of uracil into the genome in distinct manners. The atomic
      structures of these proteins complexed with substrate analogs reveal the
      structural basis for uracil recognition and suggest a novel mechanism of DNA
      repair.

PMID- 8994965
TI  - Structural views of phosphoinositide-specific phospholipase C: signalling the way
      ahead.
AB  - Recent structural studies of mammalian phosphoinositide-specific phospholipase C
      (PI-PLC) have begun to shed light on the mechanism whereby this family of
      effector enzymes is able to hydrolyze phospholipid substrates to yield second
      messengers. PI-PLC isozymes employ a variety of modules (PH domain, EF-hand
      domain, SH2 domain, SH3 domain and C2 domain) that are common in proteins
      involved in signal transduction to reversibly interact with membranes and protein
      components of the signalling pathways.

PMID- 8994966
TI  - Phi/psi-chology: Ramachandran revisited.

PMID- 8994967
TI  - The UmuD' protein filament and its potential role in damage induced mutagenesis.
AB  - BACKGROUND: Damage induced 'SOS mutagenesis' may occur transiently as part of the
      global SOS response to DNA damage in bacteria. A key participant in this process
      is the UmuD protein, which is produced in an inactive from but converted to the
      active form, UmuD', by a RecA-mediated self-cleavage reaction. UmuD', together
      with UmuC and activated RecA (RecA*), enables the DNA polymerase III holoenzyme
      to replicate across chemical and UV induced lesions. The efficiency of this
      reaction depends on several intricate protein-protein interactions. RESULTS:
      Recent X-ray crystallographic analysis shows that in addition to forming
      molecular dimers, the N- and C-terminal tails of UmuD' extend from a globular
      beta structure to associate and produce crystallized filaments. We have
      investigated this phenomenon and find that these filaments appear to relate to
      biological activity. Higher order oligomers are found in solution with UmuD', but
      not with UmuD nor with a mutant of UmuD' lacking the extended N terminus.
      Deletion of the N terminus of UmuD' does not affect its ability to form molecular
      dimers but does severely compromise its ability to interact with a RecA-DNA
      filament and to participate in mutagenesis. Mutations in the C terminus of UmuD'
      result in both gain and loss of function for mutagenesis. CONCLUSIONS: The
      activation of UmuD to UmuD' appears to cause a large conformational change in the
      protein which allows it to form oligomers in solution at physiologically relevant
      concentrations. Properties of these oligomers are consistent with the filament
      structures seen in crystals of UmuD'.

PMID- 8994968
TI  - The structure of glucose-fructose oxidoreductase from Zymomonas mobilis: an
      osmoprotective periplasmic enzyme containing non-dissociable NADP.
AB  - BACKGROUND: The organism Zymomonas mobilis occurs naturally in sugar-rich
      environments. To protect the bacterium against osmotic shock, the periplasmic
      enzyme glucose-fructose oxidoreductase (GFOR) produces the compatible, solute
      sorbitol by reduction of fructose, coupled with the oxidation of glucose to
      gluconolactone. Hence, Z mobilis can tolerate high concentrations of sugars and
      this property may be useful in the development of an efficient microbial process
      for ethanol production. Each enzyme subunit contains tightly associated NADP
      which is not released during the catalytic cycle. RESULTS: The structure of GFOR
      was determined by X-ray crystallography at 2.7 A resolution. Each subunit of the
      tetrameric enzyme comprises two domains, a classical dinucleotide-binding domain,
      and a C-terminal domain based on a predominantly antiparallel nine-stranded beta
      sheet. In the tetramer, the subunits associate to form two extended 18-stranded
      beta sheets, which pack against each other in a face to face fashion, creating an
      extensive interface at the core of the tetramer. An N-terminal arm from each
      subunit wraps around the dinucleotide-binding domain of an adjacent subunit,
      covering the adenine ring of NADP. CONCLUSIONS: In GFOR, the NADP is found
      associated with a classical dinucleotide-binding domain in a conventional
      fashion. The NADP is effectively buried in the protein-subunit interior as a
      result of interactions with the N-terminal arm from an adjacent subunit in the
      tetramer, and with a short helix from the C-terminal domain of the protein. This
      accounts for NADP's inability to dissociate. The N-terminal arm may also
      contribute to stabilization of the tetramer. The enzyme has an unexpected
      structural similarity with the cytoplasmic enzyme glucose-6-phosphate
      dehydrogenase (G6PD). We hypothesize that both enzymes have diverged from a
      common ancestor. The mechanism of catalysis is still unclear, but we have
      identified a conserved structural motif (Glu-Lys-Pro) in the active site of GFOR
      and G6PD that may be important for catalysis.

PMID- 8994969
TI  - Crystal structure of a fungal elicitor secreted by Phytophthora cryptogea, a
      member of a novel class of plant necrotic proteins.
AB  - BACKGROUND: Elicitins form a novel class of plant necrotic proteins which are
      secreted by Phytophthora and Pythium fungi, parasites of many economically
      important crops. These proteins induce leaf necrosis in infected plants and
      elicit an incompatible hypersensitive-like reaction, leading to the development
      of a systemic acquired resistance against a range of fungal and bacterial plant
      pathogens. No crystal structures of this class of protein are available. The
      crystal structure determination of beta-cryptogein (CRY), secreted by
      Phytophthora cryptogea, was undertaken to identify structural features important
      for the necrotic activity of elicitins. RESULTS: The structure of CRY was
      determined using the multiwavelength anomalous diffraction technique and refined
      to 2.2 A resolution. The overall structure has a novel fold consisting of six
      alpha helices and a beak-like motif, whose sequence is highly conserved within
      the family, composed of an antiparallel two-stranded beta sheet and an omega
      loop. This motif is assumed to be a major recognition site for a putative
      receptor and/or ligand. Two other distinct binding sites seem to be correlated to
      the level of necrotic activity of elicitins. CONCLUSIONS: The determination of
      the crystal structure of a member of the elicitin family may make it possible to
      separate the activity that causes leaf necrosis from that inducing systemic
      acquired resistance to pathogens, making it feasible to engineer a non-toxic
      elicitin that only elicits plant defences. Such studies should aid the
      development of non-toxic agricultural pest control.

PMID- 8994970
TI  - Substrate mimicry in the active center of a mammalian alpha-amylase: structural
      analysis of an enzyme-inhibitor complex.
AB  - BACKGROUND: alpha-Amylases catalyze the hydrolysis of glycosidic linkages in
      starch and other related polysaccharides. The alpha-amylase inhibitor (alpha-Al)
      from the bean Phaseolus vulgaris belongs to a family of plant defence proteins
      and is a potent inhibitor of mammalian alpha-amylases. The structure of pig
      pancreatic alpha-amylase (PPA) in complex with both a carbohydrate inhibitor
      (acarbose) and a proteinaceous inhibitor (Tendamistat) is known, but the
      catalytic mechanism is poorly understood. RESULTS: The crystal structure of pig
      pancreatic alpha-amylase complexed with alpha-Al was refined to 1.85 A
      resolution. It reveals that in complex with PPA, the inhibitor has the typical
      dimer structure common to legume lectins. Two hairpin loops extending out from
      the jellyroll fold of a monomer interact directly with the active site region of
      the enzyme molecule, with the inhibitor molecule filling the whole substrate
      docking region of the PPA. The inhibitor makes substrate-mimetic interactions
      with binding subsites of the enzyme and targets catalytic residues in the active
      site. Binding of inhibitor induces structural changes at the active site of the
      enzyme. CONCLUSIONS: The present analysis reveals that there are extensive
      interactions between the inhibitor and residues that are highly conserved in the
      active site of alpha-amylases; alpha-Al1 inactivates PPA through elaborate
      blockage of substrate-binding sites. It provides a basis to design peptide
      analogue inhibitors. alpha-Amylase inhibition is of interest from several points
      of view, for example the treatment of diabetes and for crop protection.

PMID- 8994971
TI  - Zinc mediated dimer of human interferon-alpha 2b revealed by X-ray
      crystallography.
AB  - BACKGROUND: The human alpha-interferon (huIFN-alpha) family displays broad
      spectrum antiviral, antiproliferative and immunomodulatory activities on a
      variety of cell types. The diverse biological activities of the IFN-alpha's are
      conveyed to cells through specific interactions with cell-surface receptors.
      Despite considerable effort, no crystal structure of a member of this family has
      yet been reported, because the quality of the protein crystals have been
      unsuitable for crystallographic studies. Until now, structural models of the IFN
      alpha's have been based on the structure of murine IFN-beta (muIFN-beta). These
      models are likely to be inaccurate, as the amino acid sequence of muIFN-beta
      differs significantly from the IFN-alpha's at proposed receptor-binding sites.
      Structural information on a huIFN-alpha subtype would provide an improved basis
      for modeling the structures of the entire IFN-alpha family. RESULTS: The crystal
      structure of recombinant human interferon-alpha 2b (huIFN-alpha 2b) has been
      determined at 2.9 A resolution. HuIFN-alpha 2b exists in the crystal as a
      noncovalent dimer, which associates in a novel manner. Unlike other structurally
      characterized cytokines, extensive interactions in the dimer interface are
      mediated by a zinc ion (Zn2+). The overall fold of huIFN-alpha 2b is most similar
      to the structure of muIFN-beta. Unique to huIFN-alpha 2b is a 3(10) helix in the
      AB loop which is held to the core of the molecule by a disulfide bond.
      CONCLUSIONS: The structure of huIFN-alpha 2b provides an accurate model for
      analysis of the > 15 related type 1 interferon molecules. HuIFN-alpha 2b displays
      considerable structural similarity with muIFN-beta, interleukin-10 and interferon
      gamma, which also bind related class 2 cytokine receptors. From these structural
      comparisons and numerous studies on the effects of mutations on biological
      activity, we have identified protein surfaces that appear to be important in
      receptor activation. This study also reveals the potential biological importance
      of the huIFN-alpha 2b dimer.

PMID- 8994972
TI  - Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential
      for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N
      acetylglucosamine and the drug fosfomycin.
AB  - BACKGROUND: UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), catalyses the
      first committed step of bacterial cell wall biosynthesis and is a target for the
      antibiotic fosfomycin. The only other known enolpyruvyl transferase is 5
      enolpyruvylshikimate-3-phosphate (EPSP) synthase, an enzyme involved in the
      shikimic acid pathway and the target for the herbicide glyphosate. Inhibitors of
      enolpyruvyl transferases are of biotechnological interest as MurA and EPSP
      synthase are found exclusively in plants and microbes. RESULTS: The crystal
      structure of Escherichia coli MurA complexed with UDP-N-acetylglucosamine (UDP
      GlcNAc) and fosfomycin has been determined at 1.8 A resolution. The structure
      consists of two domains with the active site located between them. The domains
      have a very similar secondary structure, and the overall protein architecture is
      similar to that of EPSP synthase. The fosfomycin molecule is covalently bound to
      the cysteine residue Cys115, whereas UDP-GlcNAc makes several hydrogen-bonding
      interactions with residues from both domains. CONCLUSIONS: The present structure
      reveals the mode of binding of the natural substrate UDP-GlcNAc and of the drug
      fosfomycin, and provides information on the residues involved in catalysis. These
      results should aid the design of inhibitors which would interfere with enzyme
      catalyzed reactions in the early stage of the bacterial cell wall biosynthesis.
      Furthermore, the crystal structure of MurA provides a model for predicting active
      site residues in EPSP synthase that may be involved in catalysis and substrate
      binding.

PMID- 8994973
TI  - A model of Ca(2+)-free calmodulin binding to unconventional myosins reveals how
      calmodulin acts as a regulatory switch.
AB  - BACKGROUND: In contrast to conventional muscle myosins, where two different light
      chains (LCs) stabilize the elongated regulatory domain (RD) region of the head
      portion of the molecule, unconventional myosins are a diverse group of motors in
      which from one to six calmodulin (CaM) subunits are bound tandemly to the RD. In
      both cases, the heavy chains of the RDs have special sequences called "IQ motifs'
      to which the LCs or CaM bind. A previously puzzling aspect of certain
      unconventional myosins is their unusual mode of regulation, where activation of
      motility occurs at low levels of Ca2+. Although the atomic structure of the
      conventional muscle myosin RD has been determined, no crystallographic structure
      of the RD of an unconventional myosin is yet available. RESULTS: We have
      constructed a model of vertebrate CaM bound to the first IQ motif present in the
      neck region of an unconventional myosin (chicken brush border myosin I), using
      strict binding rules derived from the crystal structure of the scallop RD. The
      model accounts for aspects of the regulation of many unconventional myosins where
      CaM is bound at low levels of Ca2+ and released or changed in conformation at
      high levels of Ca2+. The conformational changes as a function of Ca2+ depend not
      only on the precise sequence of the IQ motifs but also on the interactions
      between CaM molecules bound to adjacent sites on the myosin heavy chain.
      CONCLUSIONS: According to our model, the full versatility of CaM binding to
      target peptides is displayed in the regulation of unconventional myosins. At low
      concentrations of Ca2+, CaM binds in a manner similar to the LCs of conventional
      myosins. At higher Ca2+ concentrations, CaM changes conformation and acts as a
      switch to regulate the activity of the unconventional myosin molecules.

PMID- 8994974
TI  - The structural basis for pyrophosphatase catalysis.
AB  - BACKGROUND: Soluble inorganic pyrophosphatase (PPase), an essential enzyme
      central to phosphorus metabolism, catalyzes the hydrolysis of the
      phosphoanhydride bond in inorganic pyrophosphate. Catalysis requires divalent
      metal ions which affect the apparent pKas of the essential general acid and base
      on the enzyme, and the pKa of the substrate. Three to five metal ions are
      required for maximal activity, depending on pH and enzyme source. A detailed
      understanding of catalysis would aid both in understanding the nature of
      biological mechanisms of phosphoryl transfer, and in understanding the role of
      divalent cations. Without a high-resolution complex structure such a model has
      previously been unobtainable. RESULTS: We report the first two high-resolution
      structures of yeast PPase, at 2.2 and 2.0 A resolution with R factors of around
      17%. One structure contains the two activating metal ions; the other, the product
      (MnPi)2 as well. The latter structure shows an extensive network of hydrogen bond
      and metal ion interactions that account for virtually every lone pair on the
      product phosphates. It also contains a water molecule/hydroxide ion bridging two
      metal ions and, uniquely, a phosphate bound to four Mn2+ ions. CONCLUSIONS: Our
      structure-based model of the PPase mechanism posits that the nucleophile is the
      hydroxide ion mentioned above. This aspect of the mechanism is formally analogous
      to the "two-metal ion' mechanism of alkaline phosphatase, exonucleases and
      polymerases. A third metal ion coordinates another water molecule that is
      probably the required general acid. Extensive Lewis acid coordination and
      hydrogen bonds provide charge shielding of the electrophile and lower the pKa of
      the leaving group. This "three-metal ion' mechanism is in detail different from
      that of other phosphoryl transfer enzymes, presumably reflecting how ancient the
      reaction is.

PMID- 8994975
TI  - Crystal structure of vancomycin.
AB  - BACKGROUND: Vancomycin and other related glycopeptide antibiotics are clinically
      very important because they often represent the last line of defence against
      bacteria that have developed resistance to antibiotics. Vancomycin is believed to
      act by binding nascent cell wall mucopeptides terminating in the sequence D-Ala-D
      Ala, weakening the resulting cell wall. Extensive NMR and other studies have
      shown that the formation of asymmetric antibiotic dimers is important in peptide
      binding. Despite intensive efforts the crystal structure of vancomycin has been
      extremely difficult to obtain, partly because high-resolution data were
      unavailable, and partly because the structure was too large to be solved by
      conventional "direct methods'. RESULTS: Using low-temperature synchrotron X-ray
      data combined with new ab initio techniques for solving the crystallographic
      phase problem, we have succeeded in determining the crystal structure of
      vancomycin at atomic resolution. The structure provides much detailed information
      that should prove invaluable in modelling and mechanistic studies. CONCLUSIONS:
      Our structure confirms that vancomycin exists as an asymmetric dimer. The dimer
      conformation allows the docking of two D-Ala-D-Ala peptides in opposite
      directions; these presumably would be attached to different glycopeptide strands.
      In the crystal, one of the binding pockets is occupied by an acetate ion that
      mimics the C terminus of the nascent cell wall peptide; the other is closed by
      the asparagine sidechain, which occupies the place of a ligand. The occupied
      binding pocket exhibits high flexibility but the closed binding pocket is
      relatively rigid. We propose that the asparagine sidechain may hold the binding
      pocket in a suitable conformation for peptide docking, swinging out of the way
      when the peptide enters the binding pocket.

PMID- 8994976
TI  - Properties of the protein matrix revealed by the free energy of cavity formation.
AB  - BACKGROUND: The classical picture of the hydrophobic stabilization of proteins
      invokes a resemblance between the protein interior and nonpolar solvents, but the
      extent to which this is the case has often been questioned. The protein interior
      is believed to be at least as tightly packed as organic crystals, and was shown
      to have very low compressibility. There is also evidence that these properties
      are not uniform throughout the protein, and conflicting views exist on the nature
      of sidechain packing and on its influence on the properties of the protein.
      RESULTS: In order to probe the physical properties of the protein, the free
      energy associated with the formation of empty cavities has been evaluated for two
      proteins: barnase and T4 lysozyme. To this end, the likelihood of encountering
      such cavities was computed from room temperature molecular dynamics trajectories
      of these proteins in water. The free energy was evaluated in each protein taken
      as a whole and in submolecular regions. The computed free energies yielded
      information on the manner in which empty space is distributed in the system,
      while the latter undergoes thermal motion, a property hitherto not analyzed in
      heterogeneous media such as proteins. Our results showed that the free energy of
      cavity formation is higher in proteins than in both water and hexane, providing
      direct evidence that the native protein medium differs in fundamental ways from
      the two liquids. Furthermore, although the packing density was found to be higher
      in nonpolar regions of the protein than in polar ones, the free energy cost of
      forming atomic size cavities is significantly lower in nonpolar regions, implying
      that these regions contain larger chunks of empty space, thereby increasing the
      likelihood of containing atomic size packing defects. These larger empty spaces
      occur preferentially where buried hydrophobic sidechains belonging to secondary
      structures meet one another. These particular locations also appear to be more
      compressible than other parts of the core or surface of the protein. CONCLUSIONS:
      The cavity free energy calculations described here provide a much more detailed
      physical picture of the protein matrix than volume and packing calculations.
      According to this picture, the packing of hydrophobic sidechains is tight in the
      interior of the protein, but far from uniform. In particular, the packing is
      tighter in regions where the backbone forms less regular hydrogen-bonding
      interactions than at interfaces between secondary structure elements, where such
      interactions are fully developed. This may have important implications on the
      role of sidechain packing in protein folding and stability.

PMID- 8994977
TI  - Impact and evolution of minimally invasive techniques in the treatment of
      achalasia.

PMID- 8994978
TI  - One-year follow-up after laparoscopic Heller-Dor operation for esophageal
      achalasia.
AB  - BACKGROUND: The Heller-Dor operation has recently been proposed for the treatment
      of esophageal achalasia even via a laparoscopic approach. METHODS: To measure the
      medium-term effectiveness of this new minimally invasive technique, an evaluation
      of pre- and postoperative symptoms, esophagogram, endoscopic findings, esophageal
      manometry, and pH monitoring was prospectively designed in 43 patients with
      primary esophageal achalasia. The mean clinical follow-up for all the patients is
      12 months (range 3-43), while the mean radiological follow-up is 11 months (range
      1-23). Endoscopic data 1 year after surgery are currently available for 27
      patients (63%), whereas a 12-month (range 1-26) functional follow-up (including
      manometric and pH-monitoring studies of the esophagus) is currently available for
      35 patients (81.4%). RESULTS: No dysphagia was reported in 38 cases (88.4%); two
      (4.6%) complained of occasional swallowing discomfort which regressed
      spontaneously; two (4.6%) had persistent dysphagia which regressed with pneumatic
      dilatation. One patient (2.8%) reported mild occasional dysphagia after a 1-year
      asymptomatic period. Preoperatively, esophagograms showed an average maximum
      diameter of 40.6 +/- 9.1 mm which decreased to 24.1 +/- 6.0 mm after operation.
      Mean lower esophageal sphincter (LES) resting and residual pressures decreased
      significantly from 28.6 +/- 10.7 mmHg to 8.8 +/- 4.1 mmHg and from 17.0 +/- 9.7
      mmHg to 4.7 +/- 4.0 mmHg, respectively (p < 0.0001). These effects on esophageal
      diameter and LES function seem to persist over time. The complete absence of any
      peristaltic contractions recorded preoperatively in all cases remained unchanged
      after surgery in all but four patients. However, this rare recovery of
      peristalsis proved to be transient, and patients revealed a manometric impairment
      of their esophageal body function, but without complaining of dysphagia. Twenty
      four-hour pH monitoring showed abnormal gastroesophageal reflux episodes in two
      (5.7%) of the 35 patients who were monitored: one was asymptomatic; the other had
      heartburn and endoscopically demonstrated grade II esophagitis. CONCLUSIONS:
      Laparoscopic Heller-Dor operation achieves excellent medium-term results which,
      together with the already-demonstrated advantages of a minimal surgical trauma
      and rapid convalescence, validate the use of such a minimally invasive approach
      to treat patients with primary achalasia of the esophagus.

PMID- 8994979
TI  - Complications of surgical endoscopy. A decade of experience from a surgical
      residency training program.
AB  - BACKGROUND: This study examines the notion that gastrointestinal endoscopy
      performed by supervised surgical residents is safe. METHODS: We reviewed all
      gastrointestinal endoscopic procedures performed by surgical residents with
      faculty supervision for complications and deaths occurring up to 30 days
      following the procedures. RESULTS: The overall complication rate for 9,201 upper
      and lower endoscopy procedures was 1.4% and 0.42%, respectively. Overall
      mortality rate was 0.76% for upper endoscopy and 0.6% for lower endoscopy. No
      mortality was a direct result of a procedure-related complication. Intestinal
      perforation, drug overdose, bleeding, and aspiration were the most common
      procedure-related complications. Each resident completed an average of 75 upper
      endoscopies and 79 lower endoscopies during their training period. CONCLUSIONS:
      Gastrointestinal endoscopy can be performed safely by surgical residents with
      appropriate supervision. The higher morbidity and mortality of upper endoscopy
      are most likely related to the underlying disease rather than the procedure.
      Awareness of common complications and application of appropriate precautions and
      instruction are critical for minimizing complications.

PMID- 8994980
TI  - Laparoscopic screening of surgical candidates with pancreatic cancer or liver
      tumors.
AB  - BACKGROUND: Patients with colorectal or pancreatic cancers may have peritoneal
      implants which are too small to be detected by current radiologic imaging
      techniques. Since such implants often preclude surgical removal of the primary
      tumor or isolated metastasis, their detection prior to open abdominal exploration
      may spare patients the morbidity of a large abdominal incision when there is no
      benefit to resection and lifespan is limited. METHODS: In the past 30 months,
      patients with pancreatic cancer, hepatoma, or isolated colorectal cancer
      metastases, who were candidates for surgical resection on the basis of standard
      radiologic scans, were examined with the laparoscope through a 10-mm
      periumbilical incision prior to undertaking open abdominal exploration. If
      unexpected implants were noted, biopsy was obtained through a 5-mm port placed
      through a convenient site. RESULTS: Since January 1993, 11 patients with
      pancreatic carcinoma, three patients with primary hepatic malignancies, and 12
      patients with isolated metastases from colorectal cancers have undergone
      laparoscopic examination prior to celiotomy. Eight of these patients had
      unexpected peritoneal or liver involvement which precluded resection. Laparoscopy
      was successful in detecting disease in six such patients (75%). CONCLUSION:
      Although adding 20-30 min to the operative time when unrevealing, laparoscopy
      provided an effective way to avoid celiotomy in patients with carcinomatosis.

PMID- 8994981
TI  - Laparoscopic surgery during pregnancy.
AB  - BACKGROUND: Laparoscopic surgery is known for its many advantages, but the use of
      this modality during pregnancy is still under discussion. METHODS: The subjects
      in this discussion are the unknown influence of the pneumoperitoneum and the fear
      of damaging the uterus while inserting the Veress needle and trocars. In a review
      of recent literature describing laparoscopic surgery during pregnancy, no
      complications were seen. We performed four laparoscopic appendectomies and three
      laparoscopic cholecystectomies between 12 and 33 weeks estimated gestational age
      (EGA). RESULTS: All pregnancies passed without complications and ended in at-term
      deliveries of healthy babies. CONCLUSIONS: The risks, precautions to avoid them,
      and the safety of laparoscopic surgery during pregnancy are discussed in the
      light of our experience and reports in recent literature.

PMID- 8994982
TI  - Laparoscopic creation of stomas.
AB  - BACKGROUND: Some indications for laparoscopic bowel surgery are still
      controversial. However, the use of laparoscopic techniques for the treatment of
      benign disorders is less often challenged. Moreover, the morbidity of
      nonresectional procedures is less than that encountered with resectional cases.
      Therefore, stoma creation seems ideally suited to laparoscopy. The aim of our
      study was to assess the outcome of laparoscopic stoma creation. METHODS: All
      patients who underwent laparoscopic intestinal diversion were evaluated;
      parameters included age, gender, indication for the procedure, history of
      previous surgery, operative time, length of hospitalization, recovery of bowel
      function, and postoperative complications. RESULTS: Between March 1993 and
      January 1996, 32 patients of a mean age of 42.2 (range 19-72) years (14 males, 18
      females) underwent elective laparoscopic fecal diversion (25 loop ileostomy, four
      loop colostomy, three end colostomy). Indications for fecal diversion were fecal
      incontinence (n = 11), Crohn's disease (n = 6), unresectable rectal cancer (n =
      4), pouch vaginal fistula (n = 3), rectovaginal fistula (n = 2), colonic inertia
      (n = 2), radiation proctitis (n = 1), anal stenosis (n = 1), Kaposi's sarcoma of
      the rectum (n = 1), and tuberculous fistula (n = 1). Conversion was required in
      five patients (15.6%) due to the presence of adhesions (three), enterotomy (one),
      or colotomy (one). All of these five patients had undergone previous abdominal
      surgery and were operated on early in our experience. Major postoperative
      complications occurred in two patients (6%) and in both cases consisted of stoma
      outlet obstruction after construction of a loop ileostomy. One of the two
      patients had undergone prior surgery. This patient required reoperation, at which
      time a rotation of the terminal ileum at the stoma site was found. The other
      patient had a narrow fascial opening which was successfully managed with 2 weeks
      of self-intubation of the stoma. The mean operative time was 76 (range 30-210)
      min; mean length of hospitalization was 6.2 (range 2-13) days; stoma function
      started after a mean of 3.1 (range 1-6) days. Patients with previous abdominal
      surgery had a longer mean operative time (14/32; 117 min) compared to patients
      who had no previous surgery (18/32; 55 min) (p < 0.0002). These longer operative
      times and hospital stay were attributable to extensive enterolysis, which was
      required in some cases. CONCLUSION: In conclusion, laparoscopic creation of
      intestinal stomas is safe, feasible, and effective. Although the length of the
      procedure is longer in patients who have had prior surgery, previous surgery is
      not a contraindication, and even in these cases, a laparotomy can be avoided in
      the majority of patients. Lastly, care must be taken to ensure adequate fascial
      opening and correct limb orientation.

PMID- 8994983
TI  - Intraperitoneal adhesions in laparoscopic and standard open herniorrhaphy. An
      experimental study.
AB  - BACKGROUND: Intra-abdominal complications from transabdominal properitoneal (TAP)
      laparoscopic herniorrhaphy that would not be expected to occur in an open
      herniorrhaphy are possible. In a previous study, we reported the incidence of
      significant intra-abdominal adhesions from TAP herniorrhaphies using
      polypropylene in pigs. METHODS: To compare this with an open herniorrhaphy
      technique, we performed open herniorrhaphies on 31 pigs. Additional animals
      underwent TAP herniorrhaphy with PTFE. Data were collected on operative and
      trocar-site adhesions. Graft incorporation was recorded. RESULTS: No intra
      abdominal adhesions were found in the 31 animals undergoing open herniorrhaphy.
      Fifteen adhesions were found in the 31 pigs that underwent TAP herniorrhaphy.
      These adhesions were graded and there were a total of nine significant adhesions
      with the TAP procedure. A total of 124 trocar sites resulted in two adhesions.
      Laparoscopically placed polypropylene was better incorporated than PTFE. The
      laparoscopically placed PTFE grafts commonly were poorly incorporated.
      CONCLUSIONS: We conclude that there is a risk of intraabdominal adhesions to
      either the operative site or the trocar sites in TAP herniorrhaphy that is not
      present in open techniques. One should, therefore, be circumspect in the choice
      of TAP herniorrhaphy as a primary repair.

PMID- 8994984
TI  - Herniography and ultrasonography. A prospective study comparing the effectiveness
      of laparoscopic hernia repair with extraperitoneal balloon dissection.
AB  - BACKGROUND: This study was designed to assess differences between pre- and
      postoperative herniography and ultrasonography in inguinal hernia performed
      laparoscopically with balloon dissection and mesh without suture. METHODS: Pre-
      and postoperative herniographic and ultrasonographic findings were analyzed in
      ten consecutive patients. Postoperative ultrasonography was performed on the 3rd
      and 7th days and herniography was performed on the 7th day. RESULTS: Following
      the operation both the herniography and ultrasonography were almost normalized to
      a great extent in nine patients. Overall, minimal impaired continence was
      recorded by herniography in one patient. Also, we detected nonspecific soft
      tissue thickening at the operation site in ultrasonographic examination in four
      patients. CONCLUSIONS: As for inguinal hernias, compared with other operative
      modalities of treatment, laparoscopic hernia repair with extraperitoneal balloon
      dissection and mesh without suture is a highly successful procedure and its
      minimal morbidity is well accepted by the patient.

PMID- 8994985
TI  - Laparoscopic ventral and incisional hernioplasty.
AB  - BACKGROUND: While the first laparoscopic ventral hernia repair was reported in
      1992, there have been no studies comparing laparoscopic to conventional ventral
      herniorrhaphy. METHODS: Twenty-one ventral hernias repaired laparoscopically are
      compared to a similar group of 16 patients undergoing traditional open repair
      during a 2-year period. Operative and hospital courses along with outcomes and
      cost analysis are analyzed. RESULTS: There was no statistical difference between
      groups in number of previous abdominal operations, prior hernia repairs, and
      comorbidities. Patients undergoing open repair were older with larger fascial
      defects. Open repairs had a shorter operative time as compared to the
      laparoscopic group, but statistically longer postoperative stays and costs.
      Postoperative complications occurred in 31% of the open group and 23% of the
      laparoscopic group. There were two recurrences in each group. CONCLUSIONS:
      Laparoscopic herniorrhaphy is as safe and effective as the traditional open
      technique with shorter length of stay and decreased hospital costs.

PMID- 8994986
TI  - Laparoscopic hernioplasty: why does it work?
AB  - BACKGROUND: To understand how laparoscopic hernioplasty prevents early recurrence
      of hernia, we reviewed our first 1,000 patients. We analyzed the patients by age,
      sex, and hernia type and by whether their hernia was primary or recurrent.
      METHODS: The 1,000 patients had 1,336 hernias repaired by the transabdominal
      preperitoneal or the totally extraperitoneal approach. One thousand one hundred
      seventy-three hernias were primary and 163 were recurrent. The type of hernia
      found varied with the patient's age (p < 0.001), and with whether the hernia was
      primary or recurrent (p < 0.001); 14% of primary and 27% of recurrent hernias
      were complex, a surprisingly high incidence compared to historical controls.
      RESULTS: With a median follow-up of 2 years, five hernias have recurred and all
      were due to technical errors. CONCLUSIONS: The laparoscopic repair's success may
      partially be due to its unique ability to diagnose previously overlooked complex
      elements. The defects are repaired without creating tension and the groin is
      reinforced with mesh, eliminating inherent weakness.

PMID- 8994987
TI  - Postoperative drowsiness and emetic sequelae correlate to total amount of carbon
      dioxide used during laparoscopic cholecystectomy.
AB  - BACKGROUND: After laparoscopy with carbon dioxide (CO2) insufflation early
      postoperative recovery is often complicated with drowsiness and postoperative
      nausea and vomiting (PONV). METHODS: 25 ASA I-II patients undergoing elective
      laparoscopic cholecystectomy under standardized anaesthesia were studied in a
      randomized, prospective study. The conventional CO2 pneumoperitoneum was compared
      with the mechanical abdominal wall lift (AWL) method with minimal CO2
      insufflation with special reference to postoperative recovery. RESULTS:
      Postoperative drowsiness was of a significantly longer duration with the
      conventional method (p < 0.001) compared with the AWL technique. There was a
      positive correlation with the total amount of CO2 used and the duration of
      drowsiness (r = 0.75, p < 0.01). PONV was seen significantly more often in
      patients with CO2 insufflation of more than 121 (p < 0.05). CONCLUSIONS: Avoiding
      excessive CO2 is beneficial for smoother and more uneventful recovery after
      laparoscopic cholecystectomy.

PMID- 8994989
TI  - Determination of the learning curve of the AESOP robot.
AB  - BACKGROUND: As the variety of procedures performed with laparoscopic technology
      increases, the skill levels and equipment demands also increase. Laparoscopic
      appendectomy, hernia repair, colon resection, and Nissen fundoplication all
      require someone whose only responsibility is to control the laparoscope and
      therefore the operative field. This is usually the most inexperienced person on
      the operating team. The Automated Endoscope System for Optimal Positioning
      (AESOP) robot provides a means to eliminate the need for the camera person,
      returns control of the camera and operative field to the operating surgeon, and
      enhances human performance. The purpose of this study was to evaluate the
      acquisition of skills to control the laparoscope in a satisfactory fashion.
      METHODS: We selected medical students as our study group because they have no
      prior experience in laparoscopic procedures. They performed a readily
      reproducible task in a pelvic trainer with hand control and with the AESOP robot.
      Their initial times are compared, as is the improvement in their times after 10
      min of practice with the AESOP robot. RESULTS: These data show that in this study
      group use of the AESOP robot was not as fast as hand control but the skill to use
      it was learned as quickly. Additional features of the robut such as a steady view
      and the ability to acquire images and return to them reliably are other
      advantages. CONCLUSION: The AESOP robotic arm provides a stable support for the
      laparoscope during laparoscopic procedures which can be manipulated by the
      surgeon. We found that the time required to learn control of the laparoscope
      manually and with the AESOP robot is equal.

PMID- 8994988
TI  - Staple penetration and staple histological response for attaching an epimysial
      electrode onto the abdominal surface of the diaphragm using a laparoscopic
      approach.
AB  - BACKGROUND: Laparoscopic stapling was found to be a viable option for attaching
      epimysial electrodes onto the abdominal surface of the diaphragm. Stapling was
      preferable to suturing due to its simplicity and speed. METHODS: Of the two
      staplers tested in this study, the Ethicon Endopath was preferred over the
      Autosuture Endo Hernia because the staples did not penetrate the diaphragm when
      an electrode tab thickness greater than 0.75 mm was used. RESULTS: The thickness
      of the electrode tab was an important factor in determining staple penetration
      but large variation in penetration depth indicated that other factors may also
      play a role. An electrode tab thickness of 1.0-1.25 mm was suggested to minimize
      the risk of diaphragm perforation. CONCLUSIONS: The histological reaction to
      staples implanted up to 14 months was unremarkable, reflecting the safety of
      laparoscopic staples for permanently anchoring electrodes on the diaphragm.

PMID- 8994990
TI  - Laparoscopic cholecystectomy in 1994. Results of a prospective survey conducted
      by SFCERO on 4,624 cases. Societe Francaise de Chirurgie Endoscopique et
      Radiologie Operatoire.
AB  - BACKGROUND: In 1996, laparoscopic cholecystectomy is the gold standard for
      symptomatic cholelithiasis. The results of this operation as published so far
      include data on the learning curve of the method. The aim of this study is to
      evaluate the results of laparoscopic cholecystectomy when performed by a large
      number of surgeons during the year 1994, not taking into account the beginning
      years in which the technique was being used. METHODS: This study has been carried
      out prospectively and anonymously among members of SFCERO. All the patients who
      underwent a cholecystectomy started laparoscopically during 1994 have been
      included. RESULTS: Some 4,624 cholecystectomies were performed by 150 surgeons.
      There were 3,310 females (42.5 +/- 19.8 years old) and 1,314 males (56.3 +/- 1.61
      years old). The conversion rate was 6.9%: 320 operations had to be converted into
      laparotomy (group II) while 4,261 were performed entirely by laparoscopy (group
      I). Morbidity was 5% (N = 230)-4.7% in group I (N = 203) and 8.4% in group II (N
      = 27). Mortality was 0.2% (N = 9)--namely four intraabdominal complications
      (three cases of peritonitis and one biliary re-operation), two cardiac failures,
      and one brain infarction. The causes of death were not specified in two patients.
      CONCLUSIONS: These results show that morbidity and mortality have not changed
      dramatically since the beginnings of this technique, whereas the frequency of
      common bile duct (CBD) injuries has decreased. However, the conversion rate has
      increased slightly. These results make it possible to calculate the risk of
      conversion and postoperative complication according to the age of the patient and
      the biliary symptoms.

PMID- 8994991
TI  - Is it necessary to retrieve dropped gallstones during laparoscopic
      cholecystectomy?
AB  - BACKGROUND: An experimental study was planned to evaluate the effect of bile
      alone and bile in combination with gallstones on intraperitoneal adhesion and
      abscess formation in the peritoneal cavity of the rat. METHODS: One hundred
      Sprague-Dawley rats were assigned to ten groups (n: 10). Groups 1-3 received a 1
      ml intraperitoneal injection of saline, sterile bile, and infected bile. Groups 4
      10 underwent a lower 5-mm midline abdominal incision. In groups 5, 7, and 9, a
      single gallstone (3-mm diameter) was placed in the right upper quadrant and
      injected with sterile saline, sterile bile, and infected bile, respectively. In
      groups 6, 8, and 10, four gallstones (3-mm diameter) were placed in the right
      upper quadrant together with sterile saline, sterile bile, and infected bile,
      respectively. Group 4 only underwent a 5-mm midline incision. All animals were
      sacrificed at the end of 4 weeks and the peritoneal cavity was carefully examined
      to investigate adhesions and abscess formation. The adhesions were graded
      according to Nair's gross pathologic grading of adhesions. The Kruskal-Wallis
      nonparametric test (KW) was used for statistical analysis. RESULTS: No
      intraabdominal lesions were noted in groups 1-3. The adhesion score was increased
      by number of stone and infected bile (G4: 3, G5: 3, G6: 11, G7: 7, G8: 10, G9:
      15, G10: 18). But there was only a significant difference between the groups that
      received sterile saline+single stone (G5) and that receiving infected bile+four
      stones (G10) (KW: 24.3 P < 0.05). There was abscess formation in three rats in
      group 9 and two in group 10. CONCLUSIONS: In conclusion, infected bile in
      combination with multiple stones increases the gross grading of adhesion and
      intraabdominal abscess formation. Thus, in cases with multiple stones and
      infected bile, the dropped stones should be retrieved and the peritoneal cavity
      should be copiously irrigated during laparoscopic cholecystectomy.

PMID- 8994993
TI  - Splenic rupture from colonoscopy. A report of two cases and review of the
      literature.
AB  - Splenic injury after colonoscopy is rare. Only 15 cases previously have been
      reported in the English literature. Partial capsular avulsion is the proposed
      mechanism of injury. Any condition causing increased splenocolic adhesions may be
      a predisposing factor to splenic injury. Two cases of splenic injury following
      colonoscopy are reported in addition to a complete review of the literature.

PMID- 8994992
TI  - Laparoscopic ultrasonography during laparoscopic cholecystectomy.
AB  - BACKGROUND: This study assessed the effectiveness of laparoscopic ultrasonography
      in demonstrating biliary anatomy, confirming suspected pathology, and detecting
      unsuspected pathology. METHODS: Laparoscopic ultrasonography was performed on 48
      patients (17 M:31 M) who underwent laparoscopic cholecystectomy. An Aloka 7.5-MHz
      linear laparoscopic ultrasound transducer was used for scanning. RESULTS:
      Gallbladder stones were confirmed by laparoscopic ultrasonography in all patients
      and unsuspected pathology was found in five patients. Two patients were found to
      have common bile duct stones by laparoscopic ultrasonography and this was
      confirmed by laparoscopic cholangiography. Laparoscopic ultrasound was found to
      be helpful during dissection in four patients, particularly in a patient with
      Mirizzi syndrome. The entire common bile duct was visualized by laparoscopic
      ultrasonography in 40 patients but was poorly seen in eight patients. The mean
      time taken for the examination was 9 min (range 4-18 min). CONCLUSION:
      Laparoscopic ultrasound is useful during laparoscopic cholecystectomy.

PMID- 8994994
TI  - Thoracoscopic surgery combined with a supraclavicular approach for removing
      superior mediastinal tumor.
AB  - This report introduces our new technique of thoracoscopic surgery combined with a
      supraclavicular approach for removing superior mediastinal tumor. A 68-year-old
      woman noticed a tumor palpable in the left supraclavicular fossa. The patient had
      no pain around the neck and shoulder. A radio-opaque shadow 6 cm in diameter was
      detected in her left apical lung field on chest roentgenogram. Chest CT and MRI
      showed that the tumor was located in the superior mediastinum, extending up to
      the thoracic inlet, and there was no invasion of the surroundings. At first, a
      thoracoscopic examination was performed to assess the possibility of the
      excision. After dissecting the tumor from the mediastinal tissue and the first
      costovertebrae as far as possible by thoracoscopic surgery, a supraclavicular
      approach was used to enter the thoracic cavity. Complete resection of the tumor
      was successfully performed by thoracoscopic surgery combined with a
      supraclavicular approach. The tumor was removed in a plastic bag through the
      supraclavicular defect. Postoperative histopathology revealed that the tumor was
      a benign neurogenic one. A satisfactory follow-up of 5 postoperative days was
      observed without any complications, and the patient was discharged. The procedure
      was safe, easy, and minimally invasive to perform. Moreover, the supraclavicular
      approach could be used to add trocar port if needed.

PMID- 8994995
TI  - Vascular and cardiac protection by ramipril in spontaneously hypertensive rats:
      prevention versus regression study.
AB  - The effect of chronic oral treatment with the angiotensin converting enzyme (ACE)
      inhibitor ramipril at antihypertensive and sub-antihypertensive doses, on
      vascular morphology and function as well as left ventricular hypertrophy (LVH)
      and cardiac capillary length density was investigated in spontaneously
      hypertensive rats (SHR). Treatment was commenced before hypertension developed
      (prevention study) or in adult animals with established hypertension (regression
      study). In both studies, high-dose ramipril reduced ACE activity in plasma, heart
      and aorta, normalised blood pressure, and prevented LVH or caused regression of
      LVH. Low-dose ramipril did not prevent the development of hypertension or LVH,
      but caused an increase in cardiac capillary length density. In adult hypertensive
      animals, low-dose ramipril did not reduce blood pressure but caused regression of
      LVH. In both studies, vascular function as tested in the aortic vessels was
      improved not only after high- but also after low-dose ACE inhibitor treatment: an
      inhibition of vascular ACE was associated with attenuated vasoconstrictor
      responses to norepinephrine and enhanced dilator responses to acetylcholine and
      bradykinin. A reduction of vascular hypertrophy/hyperplasia in the mesenteric
      vessels was achieved by the antihypertensive dose of ramipril in the prevention
      but not the regression study. Our data demonstrate that an improvement of
      vascular function in SHR can be achieved by chronic ACE inhibition with ramipril
      independently of structural changes and of the antihypertensive action exerted by
      the drug. LVH was reduced even at a sub-antihypertensive dose of ramipril in the
      regression but not the prevention study. In the prevention study, however, low
      dose ramipril, like high-dose ramipril, was able to protect the heart by
      preventing cardiac microvascular rarefaction.

PMID- 8994996
TI  - ACE inhibitor use in elderly patients with systolic left ventricular dysfunction:
      problems and opportunities.
AB  - The ACE inhibitors have been found effective in reducing the morbidity and
      mortality of both post-infarction patients and those with chronic systolic left
      ventricular dysfunction. However, their use is limited--particularly in elderly
      patients because of poor tolerance partly due to bradykinin-induced side-effects
      such as renal dysfunction, first-dose hypotension, and cough. Thus, the
      introduction of the angiotensin II type I receptor antagonists--that block the
      effects of angiotensin II without increasing bradykinin concentration--may be
      particularly important in the treatment of elderly patients. The role of the
      angiotensin II type I receptor antagonists in patients with systolic left
      ventricular dysfunction is currently being explored in direct comparison with and
      in conjunction with the ACE inhibitors. Furthermore, important questions about
      the most effective dose of ACE inhibitor and ACE inhibitor use in conjunction
      with aspirin and the NSAIDs still have to be answered. Thus, although we have
      learnt much about the role of ACE inhibitors in heart failure treatment, we are
      still at an early stage in the application of this knowledge, particularly in
      elderly patients.

PMID- 8994997
TI  - Influence of ACE inhibition on left ventricular hypertrophy.
AB  - Further studies are needed to assess the true clinical impact, in terms of
      reduced morbidity and mortality, of reversed LVH in hypertensive patients.
      However, the initial results strongly indicate that either a lack of decrease or
      an increase in left ventricular mass after antihypertensive treatment is
      associated with a higher risk of cardiovascular events, the latter being
      significantly reduced and almost normalised by a complete reversal of LVH.

PMID- 8994998
TI  - Influence of ACE inhibition on the kidney function of diabetics.

PMID- 8995000
TI  - How ACE inhibitors reduce death from myocardial infarction: hypotheses from the
      AIRE study. Acute Infarction Ramipril Efficacy study.
AB  - Doctors treat patients, not populations. 'Evidence-based' practice is essential
      but extrapolation to the individual patient is always necessary and this fact is
      well illustrated by data from trials of ACE inhibitors post-myocardial
      infarction. In the AIRE (Acute Infarction Ramipril Efficacy) study, 2,006
      patients with some evidence of heart failure, even if transient, after a
      myocardial infarction, were randomised to receive oral ramipril or placebo in
      addition to standard treatment. Follow-up was for a minimum of six and an average
      of 15 months. The risk reduction in total mortality was 27% (95% CI 11-40%; p =
      0.002); approximately 40 lives might be expected to be saved for every 1000
      patients treated for one year. Benefit was apparent within weeks of starting
      treatment. Additional data from the AIRE study are considered in relation to the
      findings of other mortality trials. It is argued that ACE inhibitors offer most
      to those patients with impaired left ventricular function through a mechanism not
      related to the prevention of myocardial re-infarction.

PMID- 8994999
TI  - Medical management after myocardial infarction: an evidence-based perspective.
AB  - There are a number of effective therapies to consider for the patient after
      myocardial infarction (MI). Careful patient assessment and individualisation of
      treatment is required for maximum benefit. Key aspects of assessment include
      consideration of continuing myocardial ischaemia, evaluation of LV function,
      review of risk factors and patient circumstances relevant to rehabilitation.
      Thrombolysis for eligible patients and acute aspirin are of proven benefit and
      the priority is to minimise delay in treatment. Aspirin is indicated long term
      for all patients. Beta-blockers, ACE inhibitors and possibly nitrates are also
      beneficial, but questions remain about optimal timing and combination treatment.
      Anticoagulants should be considered in selected, high-risk patients. Education
      counselling measures should be initiated in hospital and continued with risk
      factor modification as part of rehabilitation after discharge. Priority should be
      given to smoking cessation where applicable, and to reduction of elevated serum
      cholesterol levels.

PMID- 8995001
TI  - Transdermal hormone replacement therapy: its value in various clinical
      situations. Introduction.

PMID- 8995002
TI  - Postmenopausal hormone replacement therapy and insulin metabolism: effects of
      route of administration and implications for heart disease and diabetes risk.

PMID- 8995003
TI  - Smoking and postmenopausal hormone replacement therapy.

PMID- 8995004
TI  - Oestrogen replacement therapy and risk of hepatobiliary disease in postmenopausal
      women.

PMID- 8995005
TI  - Use of transdermal oestradiol (Estraderm TTS) in hypertensive postmenopausal
      women.

PMID- 8995006
TI  - Transdermal hormone replacement therapy, serum lipids and lipoproteins.

PMID- 8995007
TI  - Pamidronate (Aredia) and zoledronate: update on clinical results. Introduction.

PMID- 8995008
TI  - Pamidronate (Aredia).

PMID- 8995009
TI  - Pamidronate in the treatment of bone metastases--the European experience.

PMID- 8995010
TI  - Pamidronate in the treatment of osteolytic bone lesions in multiple myeloma
      patients--the American experience.

PMID- 8995011
TI  - Pamidronate in the treatment of osteolytic bone metastases in breast cancer
      patients.

PMID- 8995012
TI  - Zoledronate.

PMID- 8995013
TI  - Zoledronate: the preclinical pharmacology.

PMID- 8995014
TI  - Zoledronate in the treatment of Paget's disease.

PMID- 8995015
TI  - Zoledronate in the treatment of osteolytic bone metastases.

PMID- 8995016
TI  - The GH/IGF-I axis in puberty.
AB  - Puberty, either spontaneous, precocious or pharmacologically induced has profound
      effects on the physiology of the GH/IGF-I axis. Both spontaneous and stimulated
      GH secretion increase with puberty. The increase in spontaneous GH secretion is
      the result of increased GH pulse amplitude rather than frequency, and is probably
      an oestrogen-dependent effect. Parallel to the increase in GH secretion at
      puberty, circulating IGF-I and IGF binding protein-3 also increase. The pubertal
      increase in IGF-I correlates with stages of puberty as well as sex steroid
      levels. Circulating immunoreactive GHRH also increases with puberty, while
      circulating GH-binding protein levels are not affected by sexual maturation.
      Several data suggest an important role for the GH/IGF-I axis in the pubertal
      growth spurt. More recent data, however, have provided evidence of an important
      role for gonadal hormones in promoting adolescent growth independent of GH.

PMID- 8995017
TI  - Use of recombinant human growth hormone (rhGH) in pubertal patients with
      CRI/dialysis/post-transplant: Dutch data. Dutch Study Group on Growth in Children
      with Chronic Renal Disease.
AB  - In the intermediate term, recombinant human growth hormone (rhGH) therapy in a
      dose of 28-30 i.u./m2/week accelerates growth significantly in most pubertal
      patients with growth retardation secondary to chronic renal insufficiency (CRI),
      dialysis and after renal transplantation (RTx), without evidence of adverse
      effects or acceleration of bone maturation. Therefore, rhGH therapy may well
      improve the final height of these patients.

PMID- 8995018
TI  - Effect of growth hormone treatment on pubertal growth in a boy with cystinosis
      and growth failure after renal transplantation.
AB  - Recombinant human growth hormone (rhGH) has proven effective in improving growth
      in short prepubertal children with chronic renal failure (CRF) before and after
      renal transplantation. However, its effect in pubertal patients is still
      doubtful. We report the case of a boy with nephropathic cystinosis and persistent
      growth failure despite successful renal transplantation who was treated with rhGH
      (30 i.u./m2 body surface area/week sc) from early puberty up to final height.

PMID- 8995019
TI  - Use of recombinant human growth hormone (rhGH) in pubertal patients with renal
      disease.
AB  - Growth during puberty in renal failure and following renal transplantation is
      often poor. Treatment with rhGH improved height SDS in 13 pubertal children with
      renal disease.

PMID- 8995020
TI  - Recombinant human growth hormone (rhGH) is effective in pubertal patients.
AB  - Recombinant human growth hormone (rhGH) therapy in a dose of 28-30 i.u./m2/week
      results in a significant and sustained improvement of height in most pubertal
      patients with growth retardation secondary to chronic renal insufficiency (CRI),
      dialysis or after renal transplantation (RTx). Long-term data indicate that rhGH
      therapy leads to a significant improvement in the final height of growth-retarded
      pubertal patients after renal transplantation.

PMID- 8995021
TI  - The role of recombinant human growth hormone (rhGH) in pubertal patients.
AB  - Growth response to rhGH decreases with increasing age. Transplanted adolescents,
      however, respond to rhGH in a comparable way to that of younger children. Caution
      should be used in transplanted children who, in our experience, grow as well as
      younger children. Whether or not the use of rhGH improves final height if used
      during puberty remains unknown.

PMID- 8995022
TI  - Is the response to rhGH in peritoneal dialysis patients less effective than in
      patients with chronic renal insufficiency.
AB  - Data on the effects of rhGH treatment in children on peritoneal dialysis are
      limited. In general rhGH therapy seems to be less effective compared with results
      on patients with chronic renal failure on conservative treatment. Our experience
      suggests that rhGH can stimulate growth in children on CPD, and that the efficacy
      of such therapy is reduced after the first year of treatment, although the rhGH
      is still active.

PMID- 8995023
TI  - Is the response to rhGH in haemodialysis patients less effective than in patients
      with chronic renal failure? Societe de Nephrologie Pediatrique.
AB  - A total of 82 prepubertal children with chronic renal insufficiency and with (HD,
      n = 28) or without (CRI, n = 54) haemodialysis were treated with rhGH, 1
      i.u./kg/week. The absolute response (cm/year) was better in CRI children, but the
      growth velocity gain was similar in the two groups. In addition, the decrease in
      growth velocity during the second year on rhGH was more marked in CRI patients.

PMID- 8995024
TI  - Pathogenic mechanisms underlying the variable response to recombinant human
      growth hormone in children with chronic renal failure.
AB  - As with spontaneous growth, the height gain achieved by stimulation with
      recombinant human growth hormone (rhGH) in children with chronic renal failure
      appears to be inversely related to the degree of renal dysfunction. The secondary
      complications of CRF that may independently interfere with growth, such as
      metabolic acidosis, anaemia, and secondary hyperparathyroidism, do not explain
      the poorer response to rhGH in children with end-stage renal failure. Certain
      abnormalities of the somatotropic hormone axis, the severity of which is related
      to the degree of renal dysfunction, are more likely to explain the dependence of
      the rhGH treatment response on glomerular filtration rate. These derangements
      include partial GH receptor deficiency, increased plasma binding of IGF-I, and
      accumulation of non-competitive inhibitors of IGF-I action. Strategies to
      optimise growth-promoting treatment in end-stage renal failure will depend on the
      relative contribution of these different somatotropic hormone axis alterations to
      uraemia.

PMID- 8995025
TI  - rhGH use in children with CRI and undergoing dialysis post-transplant in Japan: a
      multicentre study. MultiCenter Study Group Japan.
AB  - We evaluated the effect of rhGH at both 0.5 and 1.0 i.u./kg/week, on the growth
      of 83 CRI (pre- and dialysis) and 23 transplanted children after one year. Growth
      velocity (GV) was significantly increased in predialysis children on a dose of
      0.5 i.u. (p < 0.001), from 3.8cm/year at baseline to 7.8cm/year at six months and
      7.3cm/year at one year. On a dose of 1.0 i.u., GV was increased from 4.5cm/year
      at baseline to 10.3cm/year at six months and 8.7cm/year at one year (p < 0.01).
      When the increment in GV was compared a significant difference was noted between
      0.5 i.u. and 0.1 i.u. at both six and 12 months (p < 0.01). GV was also
      significantly increased in dialysed children treated with 0.5 i.u., from
      3.5cm/year to 5.6cm/year at six months (p < 0.01) and 5.4cm/year at one year (p <
      0.01). On a dose of 1.0 i.u., the increase was from 3.4 to 8.4cm/year at six
      months (p < 0.001) and 8.3cm/year at one year (p < 0.01). There was a significant
      difference in GV between the 0.5 and 1.0 i.u. groups at both six and 12 months (p
      < 0.01). In transplanted children, GV was significantly improved over one year of
      GH treatment from 5.0 to 7.7cm/year at 0.5 i.u. (p < 0.05) and from 3.7 to
      6.3cm/year at 1.0 i.u. (p < 0.05); however, there was no statistical difference
      between the groups. Seven out of 23 children showed evidence of deterioration of
      graft function during rhGH treatment. This was due to acute rejection (AR) in
      every case. AR was noted in two of 10 children (20%) in the 0.5 i.u. group and
      five of 13 children (38%) in the 1.0 i.u. group. Our results demonstrate that
      rhGH effectively stimulates GV, not only in CRI, but also in dialysed children.
      Attention should, however, be paid to deterioration of renal function.

PMID- 8995026
TI  - Causes of failure to respond to recombinant human growth hormone (rhGH).

PMID- 8995027
TI  - Predictors of the response to growth hormone in short prepubertal children post
      renal transplant. German Study Group for Growth Hormone Treatment in Children
      Post Renal Transplantation Study Group Members.
AB  - The growth response to recombinant human growth hormone (rhGH) in post-renal
      transplantation children is variable. We sought to determine predictive factors
      of this variable effect of rhGH by analysis of a homogeneous group of 16
      prepubertal children with a median age of 12.4 years (range 7.7-18.0 years). rhGH
      was given at 30 i.u./m2/week for at least one year. All children remained
      prepubertal during the study period. Height velocity increased from 2.5 +/-
      0.4cm/year to 7.4 +/- 0.5cm/year after one year of treatment (p < 0.001). The
      growth response to rhGH (height velocity after one year of rhGH) was not
      significantly correlated with the dose of prednisolone administered (range 2.3
      9.1mg/m2/day), graft function as estimated by creatinine clearances (range 19
      88ml/min/1.73m2), the degree of stunting at baseline, baseline height velocity,
      or chronological age. However, a relatively tight inverse correlation was found
      between the growth response to rhGH and the degree of bone age delay (r = 0.73, p
      < 0.005). Hence, the degree of bone age delay appears to be a helpful clinical
      predictor of response to rhGH in short prepubertal children post-renal
      transplantation.

PMID- 8995028
TI  - Can provocative growth hormone testing predict the response to recombinant human
      growth hormone (rhGH) treatment?
AB  - Treatment with rhGH has been proven to be useful in children with chronic renal
      insufficiency and stunted growth. The aim of this study was to assess the
      usefulness of endocrinological provocative testing in predicting results to rhGH
      treatment. Endocrinological investigations performed in 14 children on renal
      replacement therapy did not correlate with increment of height velocity in the
      first year of rhGH therapy. It is concluded that no endocrinological testing is
      useful before starting rhGH treatment; other predictors of the response to rhGH
      administration are needed.

PMID- 8995029
TI  - Provocative growth hormone testing is not required before initiation of rhGH
      treatment in children with renal and liver transplants.
AB  - GH provocative testing does not predict subsequent growth response, and is not
      therefore required before initiation of rhGH treatment in children with renal and
      liver transplants. However, therapeutic doses of glucocorticoids may potentially
      inhibit GH secretion in some patients, and determining GH secretory status by
      provocation tests and measuring spontaneous GH secretion is advisable at some
      point after organ Tx to exclude GH deficiency.

PMID- 8995030
TI  - Is rhGH anabolic in patients undergoing peritoneal dialysis?
AB  - The effect of rhGH treatment on protein metabolism was studied in nine
      prepubertal patients on CAPD. An improvement in nitrogen balance as evidenced by
      a falling of blood urea nitrogen and urea nitrogen appearance with a constant
      protein intake was noticed. The significant increase in serum creatinine and
      creatinine excretion with a constant weekly creatinine clearance and the increase
      in mid-arm muscle circumference were all indications of an improvement in lean
      body mass. In addition, there was an improvement in the pattern of plasma amino
      acids and an increase in serum albumin, possibly as a result of the improvement
      of protein metabolism.

PMID- 8995031
TI  - What are the clinical benefits of correcting the catabolic state in haemodialysis
      patients?
AB  - In a double-blind, placebo-controlled trial of recombinant human growth hormone
      (rhGH) comprising 20 chronic enfeebled haemodialysed patients, the clinical
      benefit of daily growth hormone treatment for six months was evaluated. Nine
      patients (five male, four female) were treated with rhGH 4 i.u./m2/day and eleven
      with placebo (seven male, four female). Their mean age was 46.5 years (range 18
      68). No difference in mean age was found between the groups. A significant
      increase in insulin-like growth factor I (IGF-I) was observed in the rhGH-treated
      group (200 to 527ng/ml, p = 0.01), while a decrease was noticed in the placebo
      group (285 to 219ng/ml, p = 0.02). S-GH did not change significantly in either
      group, and there were no differences between the two groups in terms of weight,
      haemoglobin, s-albumin, -urea or -creatinine, which all remained unchanged during
      the trial. Patients' lean body mass, as measured by DXA-scanning, increased
      significantly in the rhGH-treated group (43.4 to 46.7kg, p = 0.004), while no
      change was observed in the placebo group (44.9 to 45.2kg, p = 0.76). The changes
      in lean body mass between the two groups were significant, p = 0.001. Left
      ventricular muscle mass increased significantly (227 to 286g, p = 0.03) in the
      rhGH-treated group, but not in the placebo group (292 to 253g, p = 0.3). The
      changes in left ventricular muscle mass between the two groups were significant
      (p = 0.02). The maximal working capacity decreased slightly and insignificantly
      in both groups, when measured by bicycle ergometry. Isometric muscle contraction
      force and endurance did not change significantly in either group. Patients'
      opinion about the influence of the treatment on their general well-being and
      working capacity, evaluated blindly on a subjective scale, improved significantly
      in the rhGH-treated group (9.7 to 12.6, p = 0.02), while no change was
      experienced in the placebo group (9.9 to 10.7, p = 0.2). No difference was
      however demonstrable between the two groups (p = 0.4). Thus we conclude that
      adult patients in long-term haemodialysis treated with rhGH experienced an
      increase in their lean body mass and left ventricular muscle mass. This increase
      in muscle mass did not, however, improve muscle contraction force or endurance
      when measured objectively. The rhGH-treated patients nevertheless had a
      subjective feeling of a slight improvement in their general wellbeing.

PMID- 8995032
TI  - Can recombinant human growth hormone (rhGH) improve the adequacy of dialysis
      (KT/V)?
AB  - Dialysis adequacy as estimated by urea kinetics could lead to false
      interpretations, especially if the dialysed patient has a high growth velocity
      and a stimulated protein anabolic state as is expected during rhGH treatment.
      Assumptions made from comparison of the UKM parameters such as PCRn, KT/V and
      TACurea, which all derive from the same urea appearance, are particularly risky.
      Dialysis adequacy appreciation during rhGH treatment needs, at least, knowledge
      of urea kinetic and dietary intake, and these should not be calculated from the
      same parameters.

PMID- 8995033
TI  - Is the impact of recombinant human growth hormone (rhGH) on the plasma lipid
      profile beneficial or harmful?
AB  - Growth hormone (GH) can modulate the metabolism of lipoproteins by affecting both
      their secretion and uptake by the liver and their catabolism by lipolytic enzymes
      in plasma. Clinical studies in adults indicate that patients with GH deficiency
      have atherogenic lipoprotein profiles that are ameliorated by GH administration.
      However, in children with GH deficiency or chronic renal insufficiency (CRI),
      just modest changes in total plasma lipids and lipoprotein profiles have been
      observed. In contrast, GH administration results in a significant increase in
      lipoprotein(a) (Lp(a)) levels that does not seem to be mediated by IGF-I but
      rather by the direct effect of GH on the hepatic secretion of Lp(a). In patients
      with CRF, Lp(a) is frequently elevated and GH administration may lead to a
      further increase in plasma levels necessitating monitoring of this highly
      atherogenic particle during rhGH treatment.

PMID- 8995034
TI  - Can glucose intolerance and/or diabetes be predicted in patients treated with
      rhGH?
AB  - Various studies have convincingly shown that recombinant human growth hormone
      (rhGH) therapy accelerates growth significantly in children with growth
      retardation secondary to chronic renal insufficiency (CRI) and after renal
      transplantation (RTx). rhGH therapy appeared remarkably safe intermediate-term,
      but paediatricians are concerned about the potential adverse effects on glucose
      homeostasis and insulin action. Particularly in children with CRI and after RTx,
      pre-existing insulin resistance may be aggravated by exogenous rhGH therapy.
      Patients after RTx had significantly higher pretreatment insulin levels than
      controls (p < 0.001). Various studies in both patient groups showed that one year
      of rhGH therapy at 4 i.u./m2/day did not impair glucose tolerance but
      significantly increased plasma insulin levels (p < 0.001). No patients developed
      impaired glucose tolerance or permanent diabetes mellitus (DM), but from these
      studies, it was concluded that euglycemia was maintained at the expense of
      increased insulin levels. The long-term consequences of the compensatory
      hyperinsulinaemia are not yet known. Although permanent DM has not been reported
      in any of the rhGH trials in renal patients, it cannot be excluded that some
      patients with CRI or after RTx may develop impaired glucose tolerance and/or
      permanent DM during long-term rhGH therapy, particularly those with risk factors
      such as familial type II DM and obesity. Long-term studies, including careful
      monitoring of carbohydrate metabolism, are required.

PMID- 8995035
TI  - Does renal osteodystrophy develop and/or progress during the course of rhGH
      treatment?
AB  - Recent expansion of the use of recombinant growth hormone (GH) to non-GH
      deficient patients demands close attention to possible complications in these
      patients, including the effects on bone. Recent studies on the use of GH in
      children with chronic renal failure (CRF) provide some early data. In several
      studies of GH in CRF no significant differences in radiographic osteodystrophy
      scores, serum calcium, phosphorus or parathyroid hormone (PTH) levels between
      treated and untreated groups have been found. Alkaline phosphatase increases
      transiently. The effect of ROD on growth response has not yet been reported.
      Children with CRF treated with GH should be serially monitored for ROD with
      serial radiographs and for serum calcium, phosphorus, alkaline phosphatase and
      PTH levels.

PMID- 8995036
TI  - The influence of growth hormone treatment on bone metabolism in dialysis
      patients.
AB  - Bone formation markers, PTH intact, and bone mineral density were evaluated in 12
      children with end stage renal disease during recombinant human growth hormone
      (rhGH) treatment. Bone biopsies before rhGH therapy revealed: osteitis fibrosa in
      one patient, mild lesions in eight, adynamic bone disease in one, and a normal
      histology in two. PTH intact increased after six months of rhGH in seven
      children, and was significantly higher in them than in the control group. A
      positive correlation between PICP concentration after one month and growth
      velocity within 12 months of rhGH was found. Higher doses of vitamin D are needed
      in growing children treated with rhGH.

PMID- 8995037
TI  - Recombinant human growth hormone (rhGH) treatment of infants and young children
      with chronic renal failure.
AB  - Infants with chronic renal failure often grow badly despite medical management.
      rhGH treatment results in good catch-up growth and should be used in infants who
      do not respond to conservative management.

PMID- 8995038
TI  - Diabetes mellitus after therapy with recombinant human growth hormone (rhGH).
AB  - An eight-year-old boy developed diabetes mellitus (DM) after kidney
      transplantation. This boy had previously been treated with recombinant human
      growth hormone (rhGH) for short stature due to chronic renal failure. An impaired
      glucose tolerance was documented after one year of rhGH treatment. An oral
      glucose tolerance test returned to normal six months after the discontinuation of
      rhGH. The boy was treated again with rhGH for seven months until his
      transplantation. A high fever with an enlargement of the parotid gland was noted
      and signs of acute rejection appeared two weeks post-transplantation. Two months
      after transplantation, overt DM had developed, and he was treated with insulin.
      The insulin dose was progressively decreased and was discontinued eight months
      after transplantation.

PMID- 8995039
TI  - Benign intracranial hypertension (pseudotumour cerebri) during rhGH therapy.

PMID- 8995040
TI  - Social skills training for adults with mental retardation in job-related
      settings.
AB  - The authors discuss the rationale for social skills training for workers with
      mental retardation, definitions and behavioral standards of these skills, and
      differences in the interaction patterns between workers with and without mental
      retardation. Various intervention strategies were reviewed critically, and their
      strengths and limitations were examined. Based on these analyses, the following
      recommendations are made. First, trainees' environments of ultimate functioning
      should be considered and contextual variables assessed and used. Second, social
      validation should be conducted to identify the social behavior that needs to be
      trained. Third, some procedures that have been found effective in other areas
      might be used for social skills training for persons with mental retardation in
      job-related settings. Fourth, active programming should be included in the
      intervention package for trainees to generalize and maintain the acquired social
      skills.

PMID- 8995041
TI  - Behavior therapy empowers persons with severe mental illness.
AB  - Behavior therapy has been viewed by some as disempowering persons with severe
      mental illness (i.e., undermining their ability to make independent decisions).
      This is ironic because various behavioral strategies actually promote independent
      decision making. Behavioral interventions (a) provide a safe place for persons to
      consider their life decisions; (b) simplify the range of choices that comprise
      many of these decisions; (c) help persons with severe mental illness learn
      behaviors so that they can better meet the demands of independent decision
      making: (d) teach family members skills so that they can provide more resources
      to support independent decision making; and (e) facilitate self-control over
      behaviors and the settings in which they occur. Behavior therapists need to
      assert the important role that behavioral principles assume in empowering persons
      with mental illness so that these principles are not discarded by professionals
      who misunderstand, or otherwise stereotype, behavioral interventions.

PMID- 8995042
TI  - Spouse-aided therapy with depressed patients.
AB  - Twenty-three non-maritally distressed depressed patients who were married or
      cohabitating were randomly assigned to either individual behavioral-cognitive
      therapy or spouse-aided treatment. Both treatment conditions focused on depressed
      mood, behavioral activity, and dysfunctional cognitions, the difference being
      that in the spouse-aided treatment the partner was involved in all aspects of
      treatment, whereas in the individual condition the partner was not involved.
      MANOVAs revealed that treatment led to statistically significant improvement on
      depressed mood, behavioral activity, and dysfunctional cognitions. Treatment did
      not affect relationship variables (marital satisfaction, communication, and
      expressed emotion) for both spouses. Spouse-aided therapy was as effective as
      individual cognitive-behavior therapy.

PMID- 8995043
TI  - Physical attractiveness in schizophrenia. The mediating role of social skill.
AB  - The role of social skill in mediating perceived physical attractiveness among
      individuals with chronic schizophrenia was investigated. Twenty five inpatients
      participated in an unstructured role play. The physical attractiveness of the
      individuals was rated both before and after observation of the role play by two
      pairs of raters. Social skill was rated by a third pair of raters. The two
      ratings of physical attractiveness were only weakly correlated with one another.
      Social skill contributed variance independent of initial attractiveness to post
      role-play attractiveness. Practical implications of the findings (i.e., stigma
      issues and social skills training) are discussed.

PMID- 8995044
TI  - The relationship between self-esteem and deviant sexual arousal in nonfamilial
      child molesters.
AB  - Changes in self-esteem as a result of direct treatment were evaluated in 12
      nonfamilial child molesters, and the relationship between these changes and
      reductions in deviant arousal was assessed. Treatment enhanced self-esteem, and
      these improvements were significantly correlated with reductions in deviant
      arousal even though deviant fantasies were not targeted in treatment.
      Implications of these findings for theoretical analyses of sexual offending and
      for treatment are discussed.

PMID- 8995045
TI  - Pain behavior, spouse responsiveness, and marital satisfaction in patients with
      rheumatoid arthritis.
AB  - Although the pain behavior of some diagnostic groups has been shown to be
      reactive to social influences, the reactivity of pain behavior in a rheumatoid
      arthritis (RA) population remains an open question. The authors in this article
      combined laboratory and self-report assessment techniques to examine the extent
      to which the pain report and behavior of 52 RA patients was susceptible to
      influence of social factors within the marital unit. The authors' findings
      suggest that (a) different types of spouse responsiveness (e.g., solicitous,
      punishing) may be viewed differently by the RA population than more general
      chronic pain populations; (b) the patient's perception of spouse responsiveness
      is a significant predictor of the pain behavior, whereas the spouse's perception
      of these same behaviors is not; and (c) the patient's perception of the spouse's
      responsive behavior adds significantly to the prediction of pain behavior over a
      model based on "disease impact" variables alone.

PMID- 8995046
TI  - Making the constraints visible: testing the ecological approach to interface
      design.
AB  - A haemodynamic monitoring and control task was used to evaluate the ecological
      approach to interface design for complex high-technology environments. Guidelines
      proposed by Bennett and Flach (1992) were used to design multilevel displays that
      made visible (a) anatomical constraints, and (b) causal constraints on
      haemodynamic systems. These displays were compared with a traditional display
      that showed pressure and flow values in five separate graphs. Simulations of
      clinical problems were generated by a computer model and presented in an
      interactive computer environment. Critical care nurses and nursing students
      observed changes in pressures and flow corresponding to certain disease states
      and corrected those states using simulated drugs. For both groups, speed and
      accuracy were progressively improved by the enhanced, multilevel displays.

PMID- 8995047
TI  - Assessment of physical work load in epidemiologic studies: common measurement
      metrics for exposure assessment.
AB  - There are many possible means of determining exposure ranging from self-reports
      of physical exposure to measures of muscle activations and estimated spinal
      loads. In epidemiologic studies, issues of validity make instrumented measures
      preferable, however issues of cost and practicability tend to force investigators
      to less costly but less valid and less reliable measures of exposure, such as
      self-report questionnaires. This paper presents a method by which estimates of
      exposure from self-report questionnaires, expert observers, work sampling, video
      analysis and electromyograms can be reported in a common metric, Newtons of force
      on a tissue, and show, as an example of its application, estimation of spinal
      compression on auto workers. A common metric allows a flexible approach to
      selection of measurement methods in occupational settings: no matter which
      instrument is used the results can be combined to provide an overall picture of
      exposure. This approach to exposure assessment for the low back allows for
      comparability across studies and settings.

PMID- 8995048
TI  - The perception of spatial layout in real and virtual worlds.
AB  - As human-machine interfaces grow more immersive and graphically-oriented, virtual
      environment systems become more prominent as the medium for human-machine
      communication. Often, virtual environments (VE) are built to provide exact
      metrical representations of existing or proposed physical spaces. However, it is
      not known how individuals develop representational models of these spaces in
      which they are immersed and how those models may be distorted with respect to
      both the virtual and real-world equivalents. To evaluate the process of model
      development, the present experiment examined participant's ability to reproduce a
      complex spatial layout of objects having experienced them previously under
      different viewing conditions. The layout consisted of nine common objects
      arranged on a flat plane. These objects could be viewed in a free binocular
      virtual condition, a free binocular real-world condition, and in a static
      monocular view of the real world. The first two allowed active exploration of the
      environment while the latter condition allowed the participant only a passive
      opportunity to observe from a single viewpoint. Viewing conditions were a between
      subject variable with 10 participants randomly assigned to each condition.
      Performance was assessed using mapping accuracy and triadic comparisons of
      relative inter-object distances. Mapping results showed a significant effect of
      viewing condition where, interestingly, the static monocular condition was
      superior to both the active virtual and real binocular conditions. Results for
      the triadic comparisons showed a significant interaction for gender by viewing
      condition in which males were more accurate than females. These results suggest
      that the situation model resulting from interaction with a virtual environment
      was indistinguishable from interaction with real objects at least within the
      constraints of the present procedure.

PMID- 8995049
TI  - Frequent short rest breaks from computer work: effects on productivity and well
      being at two field sites.
AB  - Computer operators at two work sites (n = 73, n = 19) were prompted to take three
      30-s and one 3-min break from computer work each hour in addition to conventional
      rest breaks. Some operators were asked to perform stretching exercises during the
      short breaks. Mood state and musculoskeletal discomfort were assessed at each
      work site over a 2- or 3-week baseline period and a 4- or 6-week treatment
      period, respectively. Operator productivity measures were obtained from company
      records. Operators complied with about half of the added breaks but favoured 3
      min breaks over 30-s breaks. No improvement in productivity or well-being was
      found at the larger work site. At the smaller work site, productivity, eye, leg
      and foot comfort all improved when the short breaks included stretching
      exercises. These results provide evidence that frequent short breaks from
      continuous computer-mediated work can benefit worker productivity and well-being
      when the breaks integrate with task demands.

PMID- 8995050
TI  - The core histone fold: limits to functional versatility.

PMID- 8995051
TI  - Prebiotic synthesis of diaminopyrimidine and thiocytosine.
AB  - The reaction of guanidine hydrochloride with cyanoacetaldehyde gives high yields
      (40-85%) of 2,4-diaminopyrimidine under the concentrated conditions of a drying
      lagoon model of prebiotic synthesis, in contrast to the low yields previously
      obtained under more dilute conditions. The prebiotic source of cyanoacetaldehyde,
      cyanoacetylene, is produced from electric discharges under reducing conditions.
      The effect of pH and concentration of guanidine hydrochloride on the rate of
      synthesis and yield of diaminopyrimidine were investigated, as well as the
      hydrolysis of diaminopyrimidine to cytosine, isocytosine, and uracil. Thiourea
      also reacts with cyanoacetaldehyde to give 2-thiocytosine, but the pyrimidine
      yields are much lower than with guanidine hydrochloride or urea. Thiocytosine
      hydrolyzes to thiouracil and cytosine and then to uracil. This synthesis would
      have been a significant prebiotic source of 2-thiopyrimidines and 5-substituted
      derivatives of thiouracil, many of which occur in tRNA. The applicability of
      these results to the drying lagoon model of prebiotic synthesis was tested by dry
      down experiments where dilute solutions of cyanoacetaldehyde, guanidine
      hydrochloride, and 0.5 M NaCl were evaporated over varying periods of time. The
      yields of diaminopyrimidine varied from 1 to 7%. These results show that drying
      lagoons and beaches may have been major sites of prebiotic syntheses.

PMID- 8995052
TI  - Molecular phylogeny of the free-living archezoan Trepomonas agilis and the nature
      of the first eukaryote.
AB  - We have sequenced the small ribosomal subunit RNA gene of the diplozoan
      Trepomonas agilis. This provides the first molecular information on a free-living
      archezoan. We have performed a phylogenetic analysis by maximum likelihood,
      parsimony, and distance methods for all available nearly complete archezoan small
      subunit ribosomal RNA genes and for representatives of all major groups of more
      advanced eukaryotes (metakaryotes). These show Diplozoa as the earliest-diverging
      eukaryotic lineage, closely followed by microsporidia. Trepomonas proves to be
      much more closely related to Hexamita, and, to a lesser degree, to Spironucleus,
      than to Giardia. The close relationship between the free-living Trepomonas on our
      trees and the parasites Hexamita inflata and Spironucleus refutes the idea that
      the early divergence of the amitochondrial Archezoa is an artefact caused by
      parasitism. The deep molecular divergence between the three phagotrophic genera
      with two cytostomes (Hexamita, Trepomonas, Spironucleus) and the saprotrophic
      Giardia that lacks cytostomes is in keeping with the classical evidence for a
      fundamental difference in the symmetry of the cytoskeleton between the two
      groups. We accordingly separate the two groups as two orders: Distomatida for
      those with two cytostomes/cytopharynxes and Giardiida ord. nov. for Giardia and
      Octomitus that lack these, and divide each order into two families. We suggest
      that this fundamental divergence in manner of feeding and in the symmetry of the
      cytoskeleton evolved in a free-living diplozoan very early indeed in the
      evolution of the eukaryotic cell, possibly very soon after the origin of the
      diplokaryotic state (having two nuclei linked together firmly by the
      cytoskeleton) and before the evolution of parasitism by distomatids and
      giardiids, which may have colonized animal guts independently. We discuss the
      possible relationship between the two archezoan phyla (Metamonada and
      Microsporidia) and the nature of the first eukaryotic cell in the light of our
      results and other recent molecular data.

PMID- 8995053
TI  - The sequence and organization of the core histone H3 and H4 genes in the early
      branching amitochondriate protist Trichomonas vaginalis.
AB  - Among the unicellular protists, several of which are parasitic, some of the most
      divergent eukaryotic species are found. The evolutionary distances between
      protists are so large that even slowly evolving proteins like histones are
      strongly divergent. In this study we isolated cDNA and genomic histone H3 and H4
      clones from Trichomonas vaginalis. Two histone H3 and three histone H4 genes were
      detected on three genomic clones with one complete H3 and two complete H4
      sequences. H3 and H4 genes were divergently transcribed with very short
      intergenic regions of only 194 bp, which contained T. vaginalis-specific as well
      as histone-specific putative promoter elements. Southern blot analysis showed
      that there may be several more histone gene pairs. The two complete histone H4
      genes were different on the nucleotide level but encoded the same amino acid
      sequence. Comparison of the amino acid sequences of the T. vaginalis H3 and H4
      histones with sequences from animals, fungi, and plants as well as other protists
      revealed a significant divergence not only from the sequences in multicellular
      organisms but especially from the sequences in other protists like Entamoeba
      histolytica, Trypanosoma cruzi, and Leishmania infantum.

PMID- 8995054
TI  - The gag coding region of the Drosophila telomeric retrotransposon, HeT-A, has an
      internal frame shift and a length polymorphic region.
AB  - A major component of Drosophila telomeres is the retrotransposon HeT-A, which is
      clearly related to other retrotransposons and retroviruses. This retrotransposon
      is distinguished by its exclusively telomeric location, and by the fact that,
      unlike other retrotransposons, it does not encode its own reverse transcriptase.
      HeT-A coding sequences diverge significantly, even between elements within the
      same genome. Such rapid divergence has been noted previously in studies of gag
      genes from other retroelements. Sequence comparisons indicate that the entire HeT
      A coding region codes for gag protein, with regions of similarity to other insect
      retrotransposon gag proteins found throughout the open reading frame (ORF).
      Similarity is most striking in the zinc knuckle region, a region characteristic
      of gag genes of most replication-competent retroelements. We identify a subgroup
      of insect non-LTR retrotransposons with three zinc knuckles of the form: (1)
      CX2CX4HX4C, (2) CX2CX3HX4C, (3) CX2CX3HX6C. The first and third knuckles are
      invariant, but the second shows some differences between members of this
      subgroup. This subgroup includes HeT-A and a second Drosophila telomeric
      retrotransposon, TART. Unlike other gag regions, HeT-A requires a -1 frameshift
      for complete translation. Such frameshifts are common between the gag and pol
      sequences of retroviruses but have not before been seen within a gag sequence.
      The frameshift allows HeT-A to encode two polypeptides; this mechanism may
      substitute for the post-translational cleavage that creates multiple gag
      polypeptides in retroviruses. D. melanogaster HeT-A coding sequences have a
      polymorphic region with insertions/deletions of 1-31 codons and many nucleotide
      changes. None of these changes interrupt the open reading frame, arguing that
      only elements with translatable ORFs can be incorporated into the chromosomes.
      Perhaps HeT-A translation products act in cis to target the RNA to chromosome
      ends.

PMID- 8995055
TI  - Gypsy/Ty3-like elements in the genome of the terrestrial Salamander hydromantes
      (Amphibia, Urodela).
AB  - We have studied a family of long repetitive DNA sequences (Hsr1) interspersed in
      the large genome of the European plethodontid salamander Hydromantes. The
      sequence analysis of a 5-kb fragment (Hsr1A) of one member has revealed
      significant similarities with amino acidic domains of retroviruses and
      retrotransposons. The similarity of the reverse transcriptase domain and the gene
      organization identifies Hsr1A as a member of the gypsy/Ty3 class of
      retrotransposons. We hypothesize that Hsr1 sequences are vestiges of an invasion
      of the Hydromantes genome that occurred early in the evolutionary history of
      these European plethodontids. About 10(6) Hsr1 sequences are present in the large
      Hydromantes genome. This is the highest number of copies so far discovered for
      retrotransposon-like elements in eukaryote organisms.

PMID- 8995056
TI  - Scapharca inaequivalvis tetrameric hemoglobin A and B chains: cDNA sequencing and
      genomic organization.
AB  - A and B globin cDNAs from the tetrameric hemoglobin of the bivalve mollusc
      Scapharca inaequivalvis were isolated by RT-PCR and sequenced. When compared with
      the biochemical data, the deduced protein sequences revealed only one amino acid
      substitution in the B chain. In order to investigate the genomic structure of
      these invertebrate globin genes, their intronic regions were amplified by PCR.
      The two genes showed the typical two-intron/three-exon organization found in
      vertebrates and seemed to reflect the ancestral gene structure, in accordance
      with the new globin gene evolution theory proposed by Dixon and Pohajadak (Trends
      Biochem. Sci. 17:486-488, 1992). The alternative hypothesis suggested by Go
      (Nature 291:90-92, 1981), that the central intron was lost during evolution, is
      also considered. In contrast to the related clam Anadara trapezia, S.
      inaequivalvis A and B globin genes were found to be present in multiple copies
      differing in intron size. In this study we report the complete sequences of the A
      (1,471 bp) and B (2,221 bp) globin genes, giving a detailed analysis of their
      intron features.

PMID- 8995057
TI  - The promoter region of the carbamoyl-phosphate synthetase III gene of Squalus
      acanthias.
AB  - Carbamoyl-phosphate synthetase III (CPSase III) of Squalus acanthias (spiny
      dogfish) is a nuclear-encoded mitochondrial enzyme that catalyzes glutamine
      dependent formation of carbamoyl phosphate for urea synthesis. In this paper we
      report the results of cloning a 10-kb segment of genomic DNA which includes the
      region flanking the 5' end of the spiny dogfish CPSase III gene. A total of 1,295
      base pairs of sequence straddling the start codon was obtained. Primer extension
      experiments revealed that the transcription start site is the G located 114
      residues upstream of the translation start codon ATG. The first exon has 240 base
      pairs, including the 5' untranslated region, the coding sequence for the signal
      peptide (38 amino acids), and the four N-terminal amino acids of the mature
      enzyme. The boundary of the first exon and the first intron of the CPSase III
      gene is concordant with that of rat and frog (Rana catesbeiana) CPSase I, which
      have been suggested to have evolved from CPSase III. The putative TATA box
      sequence, TACAAA, is located at position -31 with an uncommonly found C at the
      third position. Two C/EBP binding site sequences, ATTCTGCAAG (-405 to -397) and
      GTGCAGTAAG (-168 to -160), were identified in the promoter region, which suggests
      that spiny dogfish CPSase III might be subjected to transactivation of
      transcription by C/EBP-related proteins, as has been reported for rat CPSase I.
      The preparation and binding of a recombinant RcC/EBP-1 protein (the R.
      catesbeiana homolog of the mammalian C/EBP alpha) to the two spiny dogfish C/EBP
      binding sequences are described. Two putative heat-shock binding elements were
      also identified in the promoter region.

PMID- 8995058
TI  - Determinants of rate variation in mammalian DNA sequence evolution.
AB  - Attempts to analyze variation in the rates of molecular evolution among mammalian
      lineages have been hampered by paucity of data and by nonindependent comparisons.
      Using phylogenetically independent comparisons, we test three explanations for
      rate variation which predict correlations between rate variation and generation
      time, metabolic rate, and body size. Mitochondrial and nuclear genes, protein
      coding, rRNA, and nontranslated sequences from 61 mammal species representing 14
      orders are used to compare the relative rates of sequence evolution. Correlation
      analyses performed on differences in genetic distance since common origin of each
      pair against differences in body mass, generation time, and metabolic rate reveal
      that substitution rate at fourfold degenerate sites in two out of three protein
      sequences is negatively correlated with generation time. In addition, there is a
      relationship between the rate of molecular evolution and body size for two
      nuclear-encoded sequences. No evidence is found for an effect of metabolic rate
      on rate of sequence evolution. Possible causes of variation in substitution rate
      between species are discussed.

PMID- 8995059
TI  - Sequence and evolutionary history of the length polymorphism in intron 1 of the
      human red photopigment gene.
AB  - The length of intron 1 of the red pigment gene is dimorphic among Africans but
      not among Caucasians or Asians. This dimorphism was found to result from the
      presence or absence of a block of 1,284 bp comprised of three Alu elements and
      328 bp of intervening unique-sequence DNA. This additional sequence in the "long"
      intron 1 of the red pigment gene was shown to have inserted into a fourth and
      older Alu element present in the "short" from of intron 1. Furthermore, the size
      and sequence of the "short" intron 1 of the red pigment gene is equivalent to
      that of the adjacent green pigment gene. The block containing the three Alu
      elements was not found in intron 1 of the red or green pigment genes of Old World
      monkeys and orangutans but was present in intron 1 of both the green and red
      pigment genes of gorillas and chimpanzees. The nucleotide sequence of this block
      in Old World primates and the estimated ages of the three elements suggest that
      their insertion occurred sequentially in the Old World monkey lineage prior to
      duplication of the ancestral X-chromosome-linked pigment gene. After gene
      duplication, deletion of the entire block containing the three Alu elements from
      one of the genes created the "short" intron variant. Unequal recombination
      between the adjacent and highly homologous red and green pigment genes may have
      resulted in the formation of the "short" intron variant of the other gene.

PMID- 8995060
TI  - A comparison of the nucleotide sequences of the adk and recA genes of pathogenic
      and commensal Neisseria species: evidence for extensive interspecies
      recombination within adk.
AB  - The sequences of the adenylate kinase gene (adk) and the RecA gene (recA) were
      determined from the same isolates of Neisseria gonorrhoeae, N. meningitidis, N.
      lactamica, N. polysaccharea, N. cinerea, N. mucosa, N. pharyngis var. flava, N.
      flavescens, and N. animalis. The patterns of sequence divergence observed at adk
      and recA were very different. Dendrograms constructed from the recA data using
      two different algorithms were statistically robust and were congruent with each
      other and with the relationships between the species previously proposed using
      other data. In contrast, the dendrograms derived from the adk data were
      noncogruent with each other, and with those from the recA data, and were
      statistically poorly supported. These results, along with the uniform
      distribution of pairwise sequence divergences between the species at adk, suggest
      there has been a history of interspecies recombination within the adk gene of the
      human Neisseria species which has obscured the phylogenetic relationships between
      the species. This view was supported by Sawyer's runs test, and the Index of
      Association (IA) between codons, which provided significant evidence for
      interspecies recombination between the adk genes from the human Neisseria
      species, but no evidence of interspecies recombination between the recA
      sequences.

PMID- 8995061
TI  - Phylogenetic relationships within caniform carnivores based on analyses of the
      mitochondrial 12S rRNA gene.
AB  - The complete 12S rRNA gene of 32 carnivore species, including four feliforms and
      28 caniforms, was sequenced. The sequences were aligned on the basis of their
      secondary structures and used in phylogenetic analyses that addressed several
      evolutionary relationships within the Caniformia. The analyses showed an
      unresolved polytomy of the basic caniform clades; pinnipeds, mustelids,
      procyonids, skunks, Ailurus (lesser panda), ursids, and canids. The polytomy
      indicates a major diversification of caniforms during a relatively short period
      of time. The lesser panda was distinct from other caniforms, suggesting its
      inclusion in a monotypic family, Ailuridae. The giant panda and the bears were
      joined on the same branch. The skunks are traditionally included in the family
      Mustelidae. The present analysis, however, showed a less close molecular
      relationship between the skunks and the remaining Mustelidae (sensu stricto) than
      between Mustelidae (sensu stricto) and Procyonidae, making Mustelidae (sensu
      lato) paraphyletic. The results suggest that the skunks should be included in a
      separate family, Mephitidae. Within the Pinnipedia, the grouping of walrus, sea
      lions, and fur seals was strongly supported. Analyses of a combined set of 12S
      rRNA and cytochrome b data were generally consistent with the findings based on
      each gene.

PMID- 8995063
TI  - Parallel evolution in radiation of Ohomopterus ground beetles inferred from
      mitochondrial ND5 gene sequences.
AB  - Molecular phylogenetic analyses using mitochondrial NADH dehydrogenase subunit 5
      (ND5) gene sequences representing all 15 species and the majority of subspecies
      or races of the Ohomopterus ground beetles from all over the Japanese archipelago
      have uncovered a remarkable evolutionary history. Clustering of the species in
      the molecular phylogenetic tree is linked to their geographic distribution and
      does not correlate with morphological characters. Taxonomically the "same"
      species or the members belonging to the same species-group fall out in more than
      two different places on the ND5 tree. Evidence has been presented against a
      possible participation of ancestral polymorphism and random lineage sorting or of
      hybrid individuals for the observed distribution of mitochondrial DNA haplotypes.
      The most plausible explanation of our results is that parallel evolution took
      place in different lineages. Most notably, O. dehaanii, O. yaconinus, and O.
      japonicus in a lineage reveal almost identical morphology with those of the
      "same" species (or subspecies) but belonging to the phylogenetically remote
      lineages.

PMID- 8995062
TI  - Pattern and timing of evolutionary divergences among hominoids based on analyses
      of complete mtDNAs.
AB  - We have examined and dated primate divergences by applying a newly established
      molecular/ paleontological reference, the evolutionary separation between
      artiodactyls and cetaceans anchored at 60 million years before present (MYBP).
      Owing to the morphological transformations coinciding with the transition from
      terrestrial to aquatic (marine) life and the large body size of the animals
      (which makes their fossils easier to find), this reference can be defined,
      paleontologically, within much narrower time limits compared to any local primate
      calibration marker hitherto applied for dating hominoid divergences. Application
      of the artiodactyl/ cetacean reference (A/C-60) suggests that hominoid
      divergences took place much earlier than has been concluded previously. According
      to a homogeneous-rate model of sequence evolution, the primary hominoid
      divergence, i.e., that between the families Hylobatidae (gibbons) and Hominidae,
      was dated at approximately 36 MYBP. The corresponding dating for the divergence
      between Pongo (orangutan) and Gorilla-Pan (chimpanzee) -Homo is approximately
      24.5 MYBP, that for Gorilla vs Homo-Pan is approximately 18 MYBP, and that for
      Homo vs Pan approximately 13.5 MYBP. The split between Sumatran and Bornean
      orangutans was dated at approximately 10.5 MYBP and that between the common and
      pygmy chimpanzees at approximately 7 MYBP. Analyses of a single gene (cytochrome
      b) suggest that the divergence within the Catarrhini, i.e., between Hominoidea
      and Old World monkeys (Cercopithecoidea), took place > 40 MYBP; that within the
      Anthropoidea, i.e., between Catarrhini and Platyrrhini (New World monkeys), > 60
      MYBP; and that between Anthropoidea and Prosimii (lemur), approximately 80 MYBP.
      These separation times are about two times more ancient than those applied
      previously as references for the dating of hominoid divergences. The present
      findings automatically imply a much slower evolution in hominoid DNA (both
      mitochondrial and nuclear) than commonly recognized.

PMID- 8995064
TI  - Early evolutionary origin of the planktic foraminifera inferred from small
      subunit rDNA sequence comparisons.
AB  - Phylogenetic analysis of five partial planktic foraminiferal small subunit (SSU)
      ribosomal (r) DNA sequences with representatives of a diverse range of eukaryote,
      archaebacterial, and eubacterial taxa has revealed that the evolutionary origin
      of the foraminiferal lineage precedes the rapid eukaryote diversification
      represented by the "crown" of the eukaryotic tree and probably represents one of
      the earliest splits among extant free-living aerobic eukaryotes. The
      foraminiferal rDNA sequences could be clearly separated from known symbionts,
      commensals, and food organisms. All five species formed a single monophyletic
      group distinguished from the "crown" group by unique foraminiferal specific
      insertions as well as considerable nucleotide distance in aligned regions.

PMID- 8995065
TI  - Antibody-antigen recognition: a canonical structure paradigm.
AB  - The antibodies of known three-dimensional structure exhibit a definite number of
      conformations (canonical structures) for five of six hypervariable loops. In the
      present study it was found that approximately 85% of the immunoglobulin sequences
      analyzed fall into a small number of canonical structure combinations,
      representing only 3% of the total possible. These structures were classified into
      six distinct groups, depending on the type of antigen with which they interact.
      Within each loop, the positions responsible for maintaining these canonical
      structures show a use frequency of amino acids that fits an inverse power law,
      whereas the use frequency of the amino acids responsible for the detailed
      antigenic specificity follows an exponential distribution. We propose an
      evolutionary interpretation that connects these data, using the fact that the
      inverse power law is generated by statistical processes of the type that yield a
      wealth curve and the fact that exponential distribution is generated by processes
      that are not biased by past history.

PMID- 8995066
TI  - Integration of retroposable elements in mammals: selection of target sites.
AB  - Genomic DNA fragments generated by the reverse transcription of cellular RNA are
      called retroposons. Because they are flanked by short repeats, mammalian
      retroposons are believed to integrate at staggered chromosomal breaks. Recently,
      a significant sequence pattern associated with the integration of Alu and ID
      repeats was identified (Jurka 1996). It is represented by the 5' TTAAAA consensus
      sequence around the 5' ends of flanking repeats of Alu, ID, as well as, of B1 and
      B2 retroposed elements as shown in this paper. This consensus is a potential
      target for enzymatic nicking which probably occurs in the complementary strand
      between 3' AA and the following 3' TTTT bases. The first four bases of the
      flanking repeats corresponding to the 3' TTTT consensus sequence show some
      sequence variations that may be affected by complementary base pairing between
      the A-rich RNA tails and the DNA target sequences prior to nicking and reverse
      transcription. We discuss potential evidence for such base pairing based on
      correlated variations in nucleotide composition of different tail and target
      regions.

PMID- 8995067
TI  - Natural course of acute pancreatitis.
AB  - Acute pancreatitis comprises, in terms of clinical, pathologic, biochemical, and
      bacteriologic data, four entities. Interstitial edematous pancreatitis and
      necrotizing pancreatitis are the most frequent clinical manifestations;
      pancreatic pseudocyst and pancreatic abscess are late complications after
      necrotizing pancreatitis, developing after 3 to 5 weeks. Determinants of the
      natural course of acute pancreatitis are pancreatic parenchymal necrosis,
      extrapancreatic retroperitoneal fatty tissue necrosis, biologically active
      compounds in pancreatic ascites, and infection of necrosis. Early in the course
      of acute pancreatitis multiple organ failure is the consequence of various
      inflammatory mediators that are released from the inflammatory process and from
      activated leukocytes attracted by pancreatic injury. During the late course,
      starting the second week, local and systemic septic complications are dominant.
      Around 80% of deaths in acute pancreatitis are caused by septic complications.
      The infection of pancreatic necrosis occurs in 8% to 12% of acute pancreatitis
      and in 30% to 40% of patients with necrotizing pancreatitis. Bacteriologic
      analysis of intraoperative smears and aspirates reveals predominantly gram
      negative germs deriving from the intestine, most frequently Escherichia coli. It
      has been confirmed that after necrotizing pancreatitis a considerable large group
      of patients suffer long-lasting exocrine and endocrine insufficiency.

PMID- 8995068
TI  - Diagnostic standards for acute pancreatitis.
AB  - An accurate history and thorough physical examination will often raise clinical
      suspicion of acute pancreatitis in the differential diagnosis of a patient
      presenting with acute abdominal pain. An accurate diagnosis is needed to
      eliminate etiologies of acute abdominal pain and to appropriately direct therapy.
      Confirmation of the diagnosis is most often made by evaluation of serum amylase
      and lipase levels. Although hyperamylasemia is found in the majority of patients
      with acute pancreatitis, other nonpancreatic acute abdominal conditions may be
      present with hyperamylasemia. CT scanning provides an accurate confirmation of
      clinical and laboratory findings and offers excellent anatomic and morphologic
      representation of the pancreas and peripancreatic tissue. The following article,
      written by the late John H.C. Ranson, presents a discussion of the modalities
      available for diagnosing acute pancreatitis.

PMID- 8995069
TI  - Acute pancreatitis: nonsurgical management.
AB  - The care of patients with severe acute pancreatitis is complex. Although numerous
      medical therapies have been proposed, few interventions have been shown to be of
      benefit in patients with severe disease. This review summarizes the nonoperative
      management of patients with acute pancreatitis, including therapies shown to be
      of little value, the role of antibiotics in patients with acute pancreatitis, the
      importance of monitoring and supportive care, and the rationale of endoscopic and
      surgical intervention.

PMID- 8995070
TI  - Acute biliary pancreatitis: diagnosis and management.
AB  - Acute biliary pancreatitis is a serious complication of biliary calculous disease
      and is associated with significant morbidity and mortality. The role of
      endoscopic retrograde cholangiopancreatography (ERCP) in the management of acute
      biliary pancreatitis has been the focus of discussion in recent years. In
      addition, the exact role of laparoscopic cholecystectomy (LC) in the management
      of acute biliary pancreatitis has not yet been fully defined. In this report, we
      evaluated a protocol of emergency ERCP (within 24 hours) for predicted severe
      attacks, early ERCP (within 72 hours) for predicted mild attacks, and interval LC
      for management of acute biliary pancreatitis. Between January 1992 and June 1995
      a total of 75 patients with acute biliary pancreatitis were managed according to
      the protocol. Bedside ultrasonography at admission diagnosed 94% of all 64
      patients with gallbladder stones, but the sensitivity of visualizing
      choledocholithiasis was low (19%). Forty-five (60%) of them were predicted to
      have a severe attack by either Ranson or glucose/urea criteria. Emergency ERCP
      and endoscopic sphincterotomy (ES) for identifiable common bile duct (CBD) or
      ampullary stones were performed on all patients predicted to have a severe attack
      within 24 hours from presentation. An early endoscopic procedure was performed on
      all patients predicted to have a mild attack within 72 hours from presentation.
      ERCP was successful in 95% of all patients, and CBD stones were detected in 52
      (69%) of them. ES and stone clearance were successful in all of these 52
      patients. The morbidity associated with the endoscopic procedure was 3%, and
      there were no deaths. All except one patient survived the attack of acute
      pancreatitis, resulting in an overall mortality of 1%. Interval LC was performed
      on 46 patients with a conversion rate of 4%. The median postoperative hospital
      stay after LC was 2 days, and there was no major intraoperative or postoperative
      morbidity or mortality. Our experience suggests that the policy of emergency ERCP
      for patients with predicted severe disease, early ERCP for patients with
      predicted mild disease, and interval LC are associated with favorable outcomes in
      patients with acute biliary pancreatitis. Acute biliary pancreatitis can be
      managed safely and effectively by a combined endoscopic and laparoscopic
      approach.

PMID- 8995071
TI  - Surgical treatment of infected necrosis.
AB  - Over the years, experience has shown that the cornerstone for improved survival
      in patients with infected pancreatic necrosis is an early, precise diagnosis
      followed by adequate drainage combined with modern intensive care management. In
      experienced hands, this goal can be achieved with different surgical approaches,
      provided that all septic collections are thoroughly removed and that
      reexploration is performed promptly if there is evidence of ongoing sepsis. If
      there is any concept preferable, and under what conditions, future large-scale
      randomized trials with precise and comparable patient stratification will have to
      demonstrate it.

PMID- 8995072
TI  - Interventional and surgical treatment of pancreatic abscess.
AB  - Pancreatic abscess is one of the infectious complications of acute pancreatitis.
      It is a collection principally containing pus, but it may also contain variable
      amounts of semisolid necrotic debris. Most of these abscesses evolve from the
      progressive liquefaction of necrotic pancreatic and peripancreatic tissues, but
      some arise from infection of peripancreatic fluid or collections elsewhere in the
      peritoneal cavity. Included also are abscesses found after surgical debridement
      and drainage of pancreatic necrosis. Although open surgical treatment of infected
      necrosis is the established treatment of choice, percutaneous drainage of
      abscesses is successful in some circumstances. We used percutaneous catheter
      drainage in 39 patients during 1987-1995. Only 9 of 29 (31%) attempts at primary
      therapy were successful; 2 patients died, and 18 required subsequent surgical
      drainage. On the other hand, 14 of 14 patients with recurrent or residual
      abscesses after surgical drainage were successfully drained percutaneously.
      Percutaneous catheter drainage of pancreatic abscesses may be useful for initial
      stabilization of septic patients, drainage of further abscesses after surgical
      intervention (especially when access for reoperation will be difficult),
      associated abscesses remote from the pancreas, and selected unilocular
      collections at a sufficient interval after necrotizing pancreatitis to have
      allowed essentially complete liquefaction.

PMID- 8995073
TI  - Late outcome after acute pancreatitis: functional impairment and gastrointestinal
      tract complications.
AB  - Functional and morphologic changes that take place in the pancreatic gland after
      an episode of acute pancreatitis have been the subject of discussion among
      experts in recent years. At the present time there are enough studies to support
      the fact that for a certain time if not permanently after acute pancreatitis a
      variable number of patients continue to show morphologic pancreatic changes in
      the pancreas and exocrine functional impairment. These changes are clearly seen
      to be related to the severity and alcoholic etiology of the pancreatitis. There
      are also indications of possible progression from acute alcoholic pancreatitis to
      chronic pancreatitis, related to severity and recurrence. It is more probable
      that it is the first instance of pancreatitis in a pancreas that has previously
      suffered asymptomatic alcohol-induced impairment. The vascular and
      gastrointestinal tract complications that make a late appearance after acute
      pancreatitis, although infrequent, on occasion confronts the patient with a high
      risk of mortality, especially in cases of perforation and hemorrhage.

PMID- 8995074
TI  - Superconducting quantum interference device magnetometer for diagnosis of
      ischemia caused by mesenteric venous thrombosis.
AB  - Although mesenteric venous thrombosis carries a better prognosis than arterial
      thrombosis, mortality and morbidity are still high. Previous studies have shown
      that the basic electrical rhythm (BER) of the bowel decreases early after
      induction of arterial ischemia. Furthermore, our studies have shown that these
      changes occur prior to pathologic changes and that they can be recorded
      noninvasively using a superconducting quantum interference device (SQUID). SQUIDs
      measure magnetic fields that are created by the electrical activity of the
      gastrointestinal smooth muscle and have been used to measure the BER of the small
      intestine in human volunteers. This study was conducted to determine if a SQUID
      could be used for early noninvasive detection of mesenteric venous ischemia in an
      animal model. Simultaneous recordings from serosal electrodes and a SQUID outside
      the abdomen were taken from anesthetized New Zealand rabbits. Recordings were
      made for 15 minutes before and 90 minutes after injection of thrombin into the
      superior mesenteric vein. The basic electrical rhythm of the small bowel dropped
      from 16.42 +/- 0.69 to 8.80 +/- 0.74 cycles per minute at 30 minutes and to 6.82
      +/- 0.722 after 90 minutes (p < 0.0001, paired t-test). The correlation
      coefficient between the SQUID and electrical recordings was 0.954 (p < 0.0001).
      These data suggest that the ischemia caused by mesenteric venous thrombosis
      results in changes in the bioelectrical activity, which can be noninvasively
      detected using a SQUID.

PMID- 8995075
TI  - Increased surface expression of CD18 and CD11b in leukocytes after tourniquet
      ischemia during elective hand surgery.
AB  - The surface expression of beta2-integrins was investigated in leukocytes from
      patients undergoing ischemia induced by tourniquet application for elective hand
      surgery. Blood samples were obtained before initiation, at the end of ischemia,
      and after 15 minutes of reperfusion from ischemic and contralateral arms of five
      patients. Comparable expression of CD18, CD11a, CD11b, and CD11c could be
      detected by immunofluorescence in leukocytes from samples drawn from either arm
      before tourniquet application. In contrast, a significant increase in the
      expression of CD18 was detectable in monocytes, granulocytes, and lymphocytes
      from the ischemic arm compared with that in the nonischemic contralateral
      control, at the end of the ischemia time (80 +/- 16 minutes). A significantly
      increased expression of CD11b, but not CD11a or CD11c, determinants was also
      observed in granulocytes and monocytes. Concomitantly, a significant reduction in
      the percentages of granulocytes in samples from ischemic areas was detectable.
      After 15 minutes of reperfusion, differences in the expression of these adhesion
      molecules were no longer significant. The expression of the genes encoding
      interleukins IL-1alpha, IL-1beta, and IL-6 and tumor necrosis factor alpha
      (TNFalpha) proinflammatory cytokines was also studied by reverse polymerase chain
      reaction (rPCR) in peripheral blood mononuclear cells (PBMCs) obtained from the
      same samples in three patients. IL-1beta or IL-6 gene expression was never
      observed. Expression of IL-1alpha and TNFalpha genes, as detected in two
      patients, was not related with induction of ischemia. However, in these patients
      expression of one or both these genes was observed in samples derived from the
      ischemic but not the control arm after 15 minutes of reperfusion. These data
      document that overexpression of adhesion molecules and sequestration of
      leukocytes take place following short ischemia times, as routinely applied
      clinically for minor surgical procedures.

PMID- 8995076
TI  - Impact of lymph node metastasis on survival with early gastric cancer.
AB  - The impact of lymph node metastasis on the survival of early gastric cancer (EGC)
      cases remains controversial. A retrospective study of 621 patients with EGC
      undergoing gastrectomy with lymphadenectomy during the period 1966-1993 was
      performed to evaluate the influence of node involvement on long-term outcomes.
      Lymph node metastasis was observed in 63 cases (10.1%). Two groups, EGC with and
      without node involvement, were compared with respect to long-term results and
      various clinicopathologic factors. The median observation period was 123 months.
      EGC cases without metastatic nodes had significantly better outcomes than those
      with node involvement in terms of overall survival as well as survival excluding
      deaths due to diseases unrelated to the primary EGC. Survival rates for EGC
      patients with node involvement did not, however, differ significantly according
      to the number of metastatic nodes. Three factors-submucosal invasion, large tumor
      size, and recurrence-were significantly related to lymph node metastasis. Age,
      sex, family history of malignancy, histologic type, and multiple occurrence of
      gastric cancer were unrelated to the prevalence of node involvement. The
      frequency of recurrence in EGC cases without node involvement was low (1.8%, 10
      of 558). Recurrence was not, however, exceptional in those with metastatic nodes
      (9.5%, 6 of 63). EGC patients with lymph node metastasis, even with only a single
      positive node, constitute a high risk group for EGC recurrence.

PMID- 8995077
TI  - Duodenal but not gastric transection disturbs motility of the sphincter of Oddi
      in the dog.
AB  - The aim of the present study was to elucidate the effect of gastric and duodenal
      transection on biliary manometry in anesthetized dogs. The basal biliary pressure
      and increase in pressure during saline perfusion at rates of 1.0 and 1.5 ml/min
      were studied in intact controls, during infusion of cholecystokinin (CCK) alone,
      and after gastric and duodenal transection. CCK dose-dependently lowered the
      basal pressure and the increase in pressure during perfusion. Gastric transection
      1.5 cm proximal to the pylorus did not affect these parameters. In contrast,
      duodenal transection 1.0 cm distal to the pylorus significantly increased these
      parameters compared to all other groups. These observations suggest that the
      proximal duodenal transection, as performed during conventional distal
      gastrectomy, may contribute to the pathogenesis of postgastrectomy gallstone
      formation by altering motor function of the sphincter of Oddi.

PMID- 8995078
TI  - Recurrence after resection for ductal adenocarcinoma of the pancreas.
AB  - We analyzed the pattern of failure and clinicopathologic factors influencing the
      disease-free survival of 78 patients who died after macroscopic curative
      resection for pancreatic cancer. Local recurrence was a component of failure in
      56 patients (71.8%) and hepatic recurrence in 48 (61.5%), both accounting for 97%
      of the total recurrence rate. About 95% of recurrences occurred by 24 months
      after operation. Median disease-free survival time was 8 months, and cumulative 1
      , 3-, and 5-year actuarial disease-free survival rates were 66%, 7%, and 3%,
      respectively. Multivariate analysis showed that tumor grade (p = 0.04),
      microscopic radicality of resection (p = 0.04), lymph node status (p = 0.01), and
      size of the tumor (p = 0.005) were independent predictors of disease-free
      survival. Patterns of failure and disease-free survival were not statistically
      influenced by the type of surgical procedure performed. Median survival time from
      the detection of recurrence until death was 7 months for local recurrence versus
      3 months for hepatic or local plus hepatic recurrence (p < 0.05). From our
      experience and the data collected from the literature, it appears that surgery
      alone is an inadequate treatment for cure in patients with pancreatic carcinoma.
      Effective adjuvant therapies are needed to improve locoregional control of
      pancreatic cancer after surgical resection.

PMID- 8995079
TI  - Changes in gallbladder surgery: comparative study 4 years before and 4 years
      after laparoscopic cholecystectomy.
AB  - Operative procedures on the gallbladder and biliary ducts have undergone a
      profound transformation since the introduction of laparoscopic techniques in
      general surgery. As the benefits of minimally invasive procedures become
      universally known, patients are seeking surgery at an earlier stage, resulting in
      an increased number of cases for elective surgery and a considerable reduction in
      emergency operations, morbidity, need for intraoperative cholangiography (IOC),
      fewer common bile duct (CBD) explorations, shortened hospital stay, and reduced
      overall costs. The early criteria for IOC and the need for CBC explorations must
      be reevaluated in view of the observed changes and appropriate modifications
      made. Looking at the present trends, it seems that the routine use of IOC is not
      justified in the average patient who presents for laparoscopic cholecystectomy
      with no history of jaundice or pancreatitis, normal liver function tests, and a
      normal-size CBD on ultrasonography. Under those conditions, the chance of leaving
      an unsuspected stone in the CBD is less than 1%; and if it happens the stone can
      be easily retrieved by endoscopic sphincterotomy as an outpatient procedure.

PMID- 8995080
TI  - Family history as a marker of risk for colorectal cancer: Austrian experience.
AB  - A family history of colorectal cancer is a known risk factor for the disease. As
      a result of different study designs from different populations, the strength of
      this association varies in the literature. We intended to define the incidence
      and the risk predictors in first-degree relatives of patients with colorectal
      cancer in the Austrian population. A family history was obtained from first
      degree relatives of 100 consecutive patients with sporadic colorectal cancer.
      Life-table methods were used to compare the observed and expected incidence of
      colorectal cancer and the influence of differences in risk for first-degree
      family members. The calculated lifetime risk for colorectal cancer in Austria is
      1:16. Individuals with a positive family history had a 4.6-fold risk (p </=
      0.0001), particularly in the case of a young index patient (p </= 0.011) or if
      two or more family members were affected (p </= 0. 001). In addition, the risk
      for gastric cancer in relatives was increased almost fourfold (p </= 0.0001). We
      have confirmed for Austria that a positive family history of colorectal cancer is
      a strong risk factor, and that this risk is comparable to that in other Western
      countries. We have shown that relatives are also at increased risk for gastric
      cancer.

PMID- 8995081
TI  - Prognostic markers for colorectal cancer: expression of P53 and BCL2.
AB  - P53 is a tumor suppressor gene that has been implicated in the pathogenesis of a
      wide range of tumor types including colorectal cancers. bcl2 is a proto-oncogene
      that inhibits apoptosis. Immunostaining for P53 and BLC2 protein product was
      performed in a retrospective series of 80 colorectal carcinomas with a minimum
      follow-up of 5 years. The aim of the study was to evaluate the prognostic
      significance of P53 and BCL2 protein expression and their correlation with
      clinicopathologic variables such as pathologic disease stage (Dukes system),
      histologic grade, and vascular invasion. The patients were 41 to 76 years of age,
      and the follow-up ranged between 5 and 10 years. Among the 80 cases, 30 were
      Dukes stage A and 50 stage B. We found vascular invasion in 21.2%. P53 and BCL2
      expression was detected, respectively, in 30.0% and 8.8%. We concluded that the
      P53 and BCL2 expression detected by immunohistochemistry in routinely processed,
      paraffin-embedded tissues: (1) has no prognostic significance; and (2) was not
      correlated with pathologic disease stage, histologic grade, or vascular invasion.
      Nevertheless, the number of patients in our study was small, and we believe that
      investigation of a larger series of patients is indicated.

PMID- 8995082
TI  - Cost of open versus laparoscopically assisted right hemicolectomy for cancer.
AB  - The aim of this study was to estimate and compare the costs of open right
      hemicolectomy (ORHC) versus laparoscopically assisted right hemicolectomy (LARHC)
      performed for cancer. A retrospective cost analysis of 61 consecutive patients
      operated on between January 1992 and August 1994 for right-sided colonic cancer
      by either LARHC (n = 28) or ORHC (n = 33) was performed. The analysis focused on
      the cost (in Australian dollars) incurred from the date of operation to the date
      of discharge. LARHC was significantly more expensive than ORHC (total cost LARHC
      $9064, ORHC $7881; p < 0.001). LARHC was associated with a significantly longer
      operating room utilization time (LARHC 261 minutes, ORHC 203 minutes; p < 0.001)
      and a greater cost of disposables (LARHC $854, ORHC $189; p < 0.001). This study
      demonstrates no cost benefit for LARHC compared to ORHC when performed for
      cancer.

PMID- 8995083
TI  - Historical evolution of inguinal hernia repair.
AB  - When analyzing original articles since the sixteenth century, it becomes apparent
      that all surgical techniques for repair of the inguinal hernial orifice can be
      traced back to two simple repair principles. The first is reinforcement of the
      anterior wall of the inguinal canal and tightening of the external inguinal ring
      (Stromayr 1559, Purmann 1694, Czerny 1877), and the second is reinforcement of
      the posterior wall of the inguinal canal and the tightening of the internal
      inguinal ring, either externally (Lucas-Championniere 1881, Bassini 1889,
      Lotheissen 1898, McVay 1942, Shouldice 1945, Lichtenstein 1987, Stoppa 1989) or
      via an intraabdominal approach by laparotomy (Tait 1891) or laparoscopically (Ger
      1990, Velez and Klein 1990). We have tried to provide a systematic order to the
      diverse procedures of surgery of inguinal hernias according to their repair
      principles. We also point out their historical development.

PMID- 8995084
TI  - The pivotal role of John S. Edkins in the discovery of gastrin.
AB  - John Sydney Edkins was born in London in 1863. After gaining two open
      scholarships, he attended Caius College, Cambridge and studied physiology under
      the tutelage of J.N. Langley and M. Foster. During this period he published on
      the chemical nature of pepsinogen with Langley. After qualifying as a medical
      doctor, he worked in Manchester before returning to London, where he succeeded E.
      Klein as Head of Physiology at St. Bartholomew's. For financial reasons he also
      worked part time at Bedford College for Women. In 1902 Bayliss and Starling
      overturned Pavlov's doctrine of the nervous regulation of gastrointestinal
      function by discovering the pancreatic secretagogue secretin-the first
      identifiable chemical messenger. Edkins applied a similar rationale to the
      stomach and in a classic series of experiments noted that injection of a pyloric
      mucous membrane extract resulted in gastric acid and pepsin secretion in
      anesthetized cats. In 1905 he named this putative active agent "gastrin."
      Although his ideas were initially accepted, the discovery of histamine in 1910
      and the identification that extracts from other tissues had a similar physiologic
      effect raised serious questions regarding the validity of the existence of
      gastrin. Somewhat discouraged, Edkins pursued the teaching and training of women
      physiologists at Bedford College, where he later became Chairman of Physiology.
      Outside of science he successfully pursued other interests and became President
      of the British Croquet Association. The demonstration that gastrin was a unique
      antral stimulant of acid secretion by Komarov in 1938 was followed by the
      purification and elucidation of its chemical structure by Gregory and Tracy in
      1964. Their work allowed final validation of Edkins' original hypothesis. Edkins
      died in London in 1940, not only fated to predecease the vindication of his
      hypothesis but unable to witness the evolution of his discovery into a paradigm
      for the hormonal regulation of secretory and proliferative cellular activity.

PMID- 8995085
TI  - Early ERCP and papillotomy compared with conservative treatment for acute biliary
      pancreatitis. The German Study Group on Acute Biliary Pancreatitis.
AB  - BACKGROUND: The role of early endoscopic retrograde cholangiopancreatography
      (ERCP) and papillotomy in the treatment of patients who have acute biliary
      pancreatitis without obstructive jaundice is uncertain. METHODS: We conducted a
      prospective, multicenter study in which 126 patients were randomly assigned to
      early ERCP (within 72 hours after the onset of symptoms) and endoscopic
      papillotomy for the removal of stones in the common bile duct, when appropriate,
      and 112 patients were assigned to conservative treatment. In the conservative
      treatment group, ERCP was performed within three weeks if signs of biliary
      obstruction or sepsis developed. Overall mortality, mortality due to
      pancreatitis, and complications were compared in the two groups. RESULTS: Early
      ERCP was successful in 121 of the 126 patients in the invasive-treatment group.
      Endoscopic papillotomy was performed to remove bile-duct stones in 58 patients;
      stones were successfully extracted in 57. ERCP was performed in 22 of the 112
      patients in the conservative-treatment group; papillotomy for stone removal was
      successful in 13 patients. Fourteen patients in the invasive-treatment group and
      7 in the conservative-treatment group died within three months (P=0.10); 10
      patients in the invasive-treatment group and 4 in the conservative-treatment
      group died from acute biliary pancreatis (P=0.16). The overall rate of
      complications was similar in the two groups, but patients in the invasive
      treatment group had more severe complications. Respiratory failure was more
      frequent in the invasive-treatment group, and jaundice was more frequent in the
      conservative-treatment group. CONCLUSIONS: In patients with acute biliary
      pancreatis but without obstructive jaundice, early ERCP and sphincterotomy were
      not beneficial.

PMID- 8995086
TI  - A prediction rule to identify low-risk patients with community-acquired
      pneumonia.
AB  - BACKGROUND: There is considerable variability in rates of hospitalization of
      patients with community-acquired pneumonia, in part because of physicians'
      uncertainty in assessing the severity of illness at presentation. METHODS: From
      our analysis of data on 14,199 adult inpatients with community-acquired
      pneumonia, we derived a prediction rule that stratifies patients into five
      classes with respect to the risk of death within 30 days. The rule was validated
      with 1991 data on 38,039 inpatients and with data on 2287 inpatients and
      outpatients in the Pneumonia Patient Outcomes Research Team (PORT) cohort study.
      The prediction rule assigns points based on age and the presence of coexisting
      disease, abnormal physical findings (such as a respiratory rate of > or = 30 or a
      temperature of > or = 40 degrees C), and abnormal laboratory findings (such as a
      pH <7.35, a blood urea nitrogen concentration > or = 30 mg per deciliter [11 mmol
      per liter] or a sodium concentration <130 mmol per liter) at presentation.
      RESULTS: There were no significant differences in mortality in each of the five
      risk classes among the three cohorts. Mortality ranged from 0.1 to 0.4 percent
      for class I patients (P=0.22), from 0.6 to 0.7 percent for class II (P=0.67), and
      from 0.9 to 2.8 percent for class III (P=0.12). Among the 1575 patients in the
      three lowest risk classes in the Pneumonia PORT cohort, there were only seven
      deaths, of which only four were pneumonia-related. The risk class was
      significantly associated with the risk of subsequent hospitalization among those
      treated as outpatients and with the use of intensive care and the number of days
      in the hospital among inpatients. CONCLUSIONS: The prediction rule we describe
      accurately identifies the patients with community-acquired pneumonia who are at
      low risk for death and other adverse outcomes. This prediction rule may help
      physicians make more rational decisions about hospitalization for patients with
      pneumonia.

PMID- 8995087
TI  - Ventricular dysfunction and the risk of stroke after myocardial infarction.
AB  - BACKGROUND: In patients who have had a myocardial infarction, the long-term risk
      of stroke and its relation to the extent of left ventricular dysfunction have not
      been determined. We studied whether a reduced left ventricular ejection fraction
      is associated with an increased risk of stroke after myocardial infarction and
      whether other factors such as older age and therapy with anticoagulants,
      thrombolytic agents, or captopril affect long-term rates of stroke. METHODS: We
      performed an observational analysis of prospectively collected data on 2231
      patients who had left ventricular dysfunction after acute myocardial infarction
      who were enrolled in the Survival and Ventricular Enlargement trial. The mean
      follow-up was 42 months. Risk factors for stroke were assessed by both univariate
      and multivariate Cox proportional-hazards analysis. RESULTS: Among these
      patients, 103 (4.6 percent) had fatal or nonfatal strokes during the study (rate
      of stroke per year of follow-up, 1.5 percent). The estimated five-year rate of
      stroke in all the patients was 8.1 percent. As compared with patients without
      stroke, patients with stroke were older (mean [+/-SD] age, 63+/-9 years vs. 59+/
      11 years; P<0.001) and had lower ejection fractions (29+/-7 percent vs. 31+/-7
      percent, P=0.01). Independent risk factors for stroke included a lower ejection
      fraction (for every decrease of 5 percentage points in the ejection fraction
      there was an 18 percent increase in the risk of stroke), older age, and the
      absence of aspirin or anticoagulant therapy. Patients with ejection fractions of
      < or = 28 percent after myocardial infarction had a relative risk of stroke of
      1.86, as compared with patients with ejection fractions of more than 35 percent
      (P=0.01). The use of thrombolytic agents and captopril had no significant effect
      on the risk of stroke. CONCLUSIONS: During the five years after myocardial
      infarction, patients have a substantial risk of stroke. A decreased ejection
      fraction and older age are both independent predictors of an increased risk of
      stroke. Anticoagulant therapy appears to have a protective effect against stroke
      after myocardial infarction.

PMID- 8995088
TI  - Neurodevelopment of children exposed in utero to antidepressant drugs.
AB  - BACKGROUND: Many women of reproductive age have depression, necessitating therapy
      with either a tricyclic antidepressant drug or a drug, such as fluoxetine, that
      inhibits the reuptake of serotonin. Whether these drugs affect fetal
      neurodevelopment is not known. METHODS: We studied the children of 80 mothers who
      had received a tricyclic antidepressant drug during pregnancy, 55 children whose
      mothers had received fluoxetine during pregnancy, and 84 children whose mothers
      had not been exposed during pregnancy to any agent known to affect the fetus
      adversely. The children's global IQ and language development were assessed
      between 16 and 86 months of postnatal age by age-appropriate Bayley Scales of
      Infant Development or the McCarthy Scales of Children's Abilities (for IQ) and
      the Reynell Developmental Language Scales. RESULTS: The mean (+/-SD) global IQ
      scores were 118+/-17 in the children of mothers who received a tricyclic
      antidepressant drug, 117+/-17 in those whose mothers received fluoxetine, and
      115+/-14 in those in the control group. The language scores were similar in all
      three groups. The results were similar in children exposed to a tricyclic
      antidepressant drug or fluoxetine during the first trimester and those exposed
      throughout pregnancy. There were also no significant differences in temperament,
      mood, arousability, activity level, distractibility, or behavior problems in the
      three groups of children. CONCLUSIONS: In utero exposure to either tricyclic
      antidepressant drugs or fluoxetine does not affect global IQ, language
      development, or behavioral development in preschool children.

PMID- 8995090
TI  - Images in clinical medicine. Cholecystoduodenal fistula.

PMID- 8995089
TI  - Successful treatment of a patient with a thymoma and pure red-cell aplasia with
      octreotide and prednisone.

PMID- 8995091
TI  - Restrictive cardiomyopathy.

PMID- 8995092
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 3-1997. A 39-year-old man with diarrhea and abdominal pain after
      chemotherapy for acute leukemia.

PMID- 8995093
TI  - Treatment of acute biliary pancreatitis.

PMID- 8995094
TI  - Prognosis and decisions in pneumonia.

PMID- 8995095
TI  - Tobacco litigation as cancer prevention: dealing with the devil.

PMID- 8995096
TI  - Uniform requirements for manuscripts submitted to biomedical journals.

PMID- 8995097
TI  - Cancer in the elderly. Epidemiologic and clinical implications.
AB  - Cancer is a major problem for the older population. The incidence of most
      malignancies increases with age, with cancer being the second most common cause
      of death in persons older than 65. With the decline in deaths related to
      cardiovascular diseases, cancer is becoming an even more prominent cause of death
      among the elderly. Despite the advances in cancer prevention and treatment over
      the past 20 years for persons under 50, the mortality has not improved for older
      persons. In this article we explore the interactions of cancer and age that may
      be of interest to the practitioner, after reviewing the epidemiology of cancer in
      the elderly.

PMID- 8995098
TI  - Prevalence of cancer in older persons living at home and in institutions.
AB  - Even though the elderly have the greatest risk of developing and dying of cancer,
      screening for cancer occurs less often in older persons. Cancer screening is
      appropriate for nursing home residents with the cognitive ability to understand
      the screening method and its implications, who do not have comorbid illnesses
      that would preclude treatment, and who have at least a five-year life expectancy.
      Screening recommendations are provided for cancers of the breast, cervix,
      prostate, colon, skin, and mouth.

PMID- 8995099
TI  - Life expectancy, comorbidity, and quality of life. A framework of reference for
      medical decisions.
AB  - The treatment of cancer in the elderly can benefit from increasingly
      sophisticated methods that measure a patient's quality of life. These measures
      are both general and cancer specific and herald a new and enlightened approach to
      patient care. The care of the older patient must be seen in light of what is
      known about life expectancy, the outcome of treatment, an awareness of
      comorbidity, and the importance of informed consent and respect for the values
      and preferences of the individual patient. This article reviews the growing
      literature on quality of life research in cancer patients.

PMID- 8995100
TI  - Cancer of the oldest old. What we have learned from autopsy studies.
AB  - Cancer in the oldest old is a novel problem, due to the recent burgeoning of the
      population aged 85 and older. This article addresses three critical questions
      related to cancer in the oldest old: Does the incidence of cancer increase after
      age 95? Is cancer a common cause of death for the oldest old? Is cancer
      accurately diagnosed in the oldest old? The authors analyzed a group of 507
      autopsies of elderly, divided in three age groups, 75 90 years, 95 99, and over
      99 (centenarians). The prevalence of cancer was 35% among the younger persons and
      20% and 16% respectively for those aged 95 99 and for the centenarians. A fourth
      of the patients in the younger group died from cancer but only 9.5% of the people
      between 95 and 98 years and 7.1% of the centenarians died from cancer. The cancer
      was the direct cause of death for 67% of the younger persons and 41% of patients
      belonging to the two oldest groups. The prevalence of metastases was 63% for
      tumors occurring in persons aged 75 90, 32% in persons aged 95 98, and 29% in the
      centenarians. Cancer had been accurately diagnosed prior to death in 67.4% of
      persons aged 75 90, in 38.5% of those aged 95 99, and 29.4% of the centenarian.
      Cancer as cause of death had been underestimated in 16% of the cases in the
      younger persons and in almost 50% of cases of the oldest old. This study suggests
      that the incidence of cancer and the importance of cancer as a cause of death may
      decline after age 95 and that the clinical diagnoses underestimate significantly
      both the incidence of cancer and the prevalence of cancer deaths in the oldest
      old.

PMID- 8995101
TI  - Molecular interactions of aging and cancer.
AB  - The increased incidence of cancer as a function of age has long been interpreted
      to suggest that multiple genetic changes are required for tumorigenesis. Cancer
      cells differ from normal cells in many characteristics, including loss of
      differentiation, increased invasiveness, and decreased drug sensitivity. Although
      recent molecular advances have helped to clarify the possible relationships
      between carcinogenesis and aging, it remains unclear whether genetic markers may
      be common to all cancer types or which markers may be associated with increased
      age of cancer patients. Fundamental aspects of cancer development for older
      people are not well understood. Further insight into the genetic factors that may
      be responsible for the initiation and progression of cancer and their connections
      to the aging process may be gained in part by studying in vitro cellular or
      replicative senescence.

PMID- 8995102
TI  - Barriers to cancer prevention in the older person.
AB  - Barriers to cancer screening are numerous and include both immutable barriers,
      such as a patient's low income, as well as more mutable barriers; fortunately,
      most barriers are potentially mutable ones. These encompass, among others, doctor
      patient communication patterns, inadequate and inaccurate health information, at
      attitudinal barriers such as patient anxiety, and community barriers, such as the
      lack of a provider reminder system to patients that prompts compliance. One of
      the easiest enablers of patient screening to implement is for clinicians to
      communicate their enthusiastic belief in screening to their older patients.
      Numerous studies now have documented the effectiveness of the physician's role in
      increasing patient compliance with screening guidelines.

PMID- 8995103
TI  - Cancer screening in the older patient.
AB  - Effective treatment of several types of malignant diseases has developed
      substantially over the past four decades, with ever improving survival rates for
      cancers found in early stages. Among older patients, however, the cancer death
      rates remain elevated. This article explores the value of early screening for
      several types of malignant disease in the older patient.

PMID- 8995104
TI  - Cancer surgery in the elderly.
AB  - Cancer surgery is safe for older patients and should not be denied on the basis
      of chronological age. The curability of cancer in the elderly is predicated on
      the individual's tolerance of major surgery. We present the physiologic changes
      that occur with aging and focus on their influence upon surgical decision making,
      the risk factors associated with cancer surgery in the elderly, the preoperative
      assessment, and perioperative care of the elderly cancer patient, as well as
      surgical considerations for specific neoplasms.

PMID- 8995105
TI  - Radiotherapy in the aged.
AB  - Radiation therapy fulfills all the requirements to be used with curative or
      palliative intent in nearly every case of cancer in the elderly. Radiotherapy is
      not associated with acute mortality in older persons and can permit organ and
      tissue preservation. The modern modalities to deliver radiotherapy treatment
      permit a large sparing of normal tissues. We need major information on
      proliferative activity of normal tissues and cancer in the elderly, on results
      according to stage of tumors, and on acute and late sequelae according to
      performance status of the patient. It is mandatory to perform prospective studies
      in order to work out protocols for oncologic treatments and specifically for
      radiotherapy, to treat adequately an increasing part of population.

PMID- 8995106
TI  - Pharmacology of cancer chemotherapy in the older person.
AB  - With more widespread use of effective chemotherapy, more elderly patients are
      candidates for treatment with cytotoxic drugs. This article reviews and discusses
      the relevant age-related factors that may alter drug disposition and its
      relationship to pharmacokinetics effects and to pharmacodynamic effects in the
      elderly.

PMID- 8995108
TI  - Symptomatic management of the older person with cancer.
AB  - The older person with cancer is often unable to participate in treatment regimens
      that a younger person might tolerate. We review the complex reasons why this may
      be so as well as provide to the reader a brief review of the major symptoms that
      can cause suffering and treatment regimens that can improve the patient's sense
      of well being. Palliative care provides the older person with advanced cancer the
      opportunity to live his or her life to the fullest during that period of life
      called dying.

PMID- 8995107
TI  - Organ preservation. An effective and safe form of cancer treatment.
AB  - In this article we review the current strategies for organ preservation in the
      treatment of cancer. Organ preservation with functional integrity is particularly
      beneficial for older patients because the need for complex functional
      rehabilitation and for the care of permanent stomas may be avoided.

PMID- 8995109
TI  - Esophageal columnar metaplasia (Barrett's esophagus).
AB  - This article explores the historical roots for the present confusion regarding
      diagnostic criteria for Barrett's esophagus. The author recommends using an
      alternative classification system for the columnar-lined esophagus that does not
      rely solely on arbitrary and imprecise endoscopic landmarks and measurements.
      Endoscopic features that suggest the presence of intestinal metaplasia in the
      esophagus are discussed and illustrated. The role of endosonography and the
      endoscopic techniques for ablating the esophageal columnar lining also are
      considered. Finally, the author lists specific management recommendations for
      patients who have esophageal columnar metaplasia.

PMID- 8995110
TI  - Precursor lesions for cancer of the cardia.
AB  - This article gives the rationale for the likelihood that the precursor lesion for
      cancer of the cardia is either short segments of Barrett's esophagus or even
      intestinalized (globlet cell change) mucosa at a normally located squamo-columnar
      junction. Intestinal metaplasia of the cardia is likely a wear and tear
      phenomenon in many individuals without gastroesophageal reflux disease (GERD).
      Markers that stratify risk further are required before routine biopsy specimens
      of the Z-line can be obtained in the clinical evaluation of patients with GERD.

PMID- 8995111
TI  - Gastric polyps as precancerous lesions.
AB  - Gastric polyps cover a wide range of possible diagnoses. Endoscopically, the
      nature of the lesions can be diagnosed with a high level of probability.
      Nevertheless, histopathological diagnosis remains mandatory. The macroscopic
      appearance of gastric polyps is described together with underlying
      histopathological diagnoses, which are determinative for subsequent treatment.

PMID- 8995113
TI  - Screening of patients with a positive family history of colorectal cancer.
AB  - A positive family history is one of the most common risk factors for colon
      cancer. The risk varies from moderately increased when a first-degree relative
      has colon cancer to high when a first-degree relative is diagnosed at an age less
      than 50 years or there are two first-degree relatives with large bowel
      malignancy. The risk of colon cancer is extreme in the rare colon cancer
      syndromes of familial adenomatous polyposis and hereditary nonpolyposis colon
      cancer. The extensive characterization of familial occurrence of colon cancer has
      led to specific screening strategies for each of these levels of familial risk.

PMID- 8995112
TI  - Significance of Helicobacter pylori infection and gastric cancer: implications
      for screening.
AB  - Helicobacter pylori infection is a major cause of premature mortality. Methods
      for diagnosing and treating this infection are now simple and reliable. A
      screening program to eradicate H. pylori is relatively straightforward to
      implement and is financially viable. This strategy initially involves a large
      capital outlay, however, and cannot be recommended until it is proven that H.
      pylori eradication reduces gastric cancer risk. It is also important to assess
      the magnitude of benefit of a screening program against the harm that might be
      engendered in terms of anxiety and adverse events from antibiotic treatment. If
      screening is beneficial, then in developed countries it could make death from H.
      pylori infection in the next century as uncommon as mortality from tuberculosis
      has been in this century.

PMID- 8995114
TI  - Screening modalities in familial adenomatous polyposis and hereditary
      nonpolyposis colorectal cancer.
AB  - The syndromes known as familial adenomatous polyposis (FAP) and hereditary
      nonpolyposis colorectal cancer (HNPCC) represent paradigms of the arguments for
      and against screening surveillance. This article details the protean
      manifestations of these conditions. It is not a how-to-do-it article with a
      suitably selected tranche of endoscopic pictures, but rather, it is an attempt to
      see what should be done.

PMID- 8995115
TI  - The problem of "flat" colonic adenoma.
AB  - In this article, differences between depressed-type early cancers and the so
      called flat adenomas are clarified.

PMID- 8995117
TI  - Surveillance of familial adenomatous polyposis patients after ileorectal
      anastomosis or ileoanal pouch anastomosis.
AB  - This article summarizes the state of affairs with respect to rectal or ileal
      polyps after colectomy in patients with familial adenomatous polyposis and
      provides some practical hints with respect to technique, follow-up, pitfalls, and
      complications of endoscopic surveillance.

PMID- 8995116
TI  - Role of upper gastrointestinal surveillance in patients with familial adenomatous
      polyposis.
AB  - Familial adenomatous polyposis (FAP) is an inherited autosomal-dominant disease
      in which hundreds and thousands of adenomas with malignant potential are found
      throughout the colon and rectum. An increased risk for benign and malignant upper
      gastrointestinal neoplasia has long been recognized in patients with FAP. In this
      article, the authors report their findings from a study of 35 registered patients
      to assess the prevalence, anatomic distribution, depth of invasion, and natural
      history of upper gastrointestinal tumors in patients with FAP.

PMID- 8995118
TI  - Screening and surveillance of ulcerative colitis.
AB  - There is an increased risk of colorectal cancer in patients who have had an
      attack of chronic ulcerative colitis, and there is evidence to suggest that
      patients with Crohn's disease are also at risk. It is difficult to give a precise
      estimate of the increased danger that patients with inflammatory bowel disease
      have over the normal population because published results are inconsistent.
      Twenty years ago patients with long-standing extensive ulcerative colitis were
      often advised to undergo proctocolectomy to protect against the development of
      cancer, but since then most physicians have adopted a policy of regular
      colonoscopic surveillance in an attempt to detect early cancer or pre-cancer.
      When published studies of surveillance results are critically analyzed, it
      appears that relatively little benefit accrues from this approach. Better methods
      of surveillance are needed to determine which individuals with chronic ulcerative
      colitis are most likely to develop cancer.

PMID- 8995119
TI  - Contributions of the molecular biologist in gastrointestinal cancer and precancer
      screening: current possibilities and future prospects.
AB  - Molecular biology has become an integral part of research aimed at improving
      diagnosis, therapy, and ultimately prevention of malignant disease. This article
      focuses on the current possibilities and limitations of molecular biology to
      improve existing screening and surveillance protocols in specific
      gastrointestinal disease entities frequently encountered in routine clinical
      practice.

PMID- 8995120
TI  - Economic aspects of endoscopic screening for intestinal precancerous conditions.
AB  - The relationship of costs to effectiveness in endoscopic screening depends on the
      incidence rate of cancers arising from precancerous lesions, the sensitivity and
      specificity rates of endoscopic screening, and the effectiveness of timely
      diagnosis and surgery in preventing death. Because all these parameters, which
      enter a medical decision analysis, have a relatively large margin of error, it is
      not possible to resolve the issue whether a screening should be performed based
      on economic analyses alone. A crude "back of the envelope" comparison of
      different screening programs suggests that colonoscopy in ulcerative colitis
      would result in the highest yield and gastroscopy of the gastric stump in the
      lowest yield.

PMID- 8995121
TI  - Renal masses: urologic management.
AB  - This article reviews the differential diagnoses for solid renal masses and
      staging for renal cell carcinoma, and also discusses several areas of controversy
      in regard to the management of solid renal masses, such as the role of nephron
      sparing surgery, extended lymphadenectomy, and ipsilateral adrenalectomy. The
      management of renal cell carcinoma associated with tumor thrombus within the vena
      cava is discussed, as are issues regarding both surgical and medical management
      (including chemotherapy and immunotherapy) of metastatic disease. Lastly, the
      emerging role of laparoscopic nephrectomy is examined.

PMID- 8995122
TI  - The kidney: radiologic-pathologic correlation.
AB  - Selected concepts of MR-pathologic correlation of renal masses are presented in
      this article by way of illustrative examples, with an emphasis on renal
      adenocarcinoma. Where applicable, practical uses of these concepts are suggested,
      particularly in those cases in which the differential diagnosis might be
      narrowed, such as in the evaluation of angiomyolipoma. Also included is a
      discussion of management decisions that may be affected by the information
      provided by MR imaging.

PMID- 8995123
TI  - Detection and staging of renal cancer.
AB  - Although MR imaging is not a first-line modality for detecting renal cancers, it
      is useful when computed tomography or ultrasound are limited by artifacts or when
      contrast media cannot be administered because of renal dysfunction or allergy. MR
      imaging is commonly used in staging renal cancers, particularly in assessing the
      presence and extent of inferior vena caval thrombus. Additionally, MR imaging can
      be useful in detecting adenopathy, hepatic metastases, direct organ invasion, and
      bony metastases to the spine. Thus, MR imaging has an established role in the
      detection and staging of renal cancers.

PMID- 8995124
TI  - Renal cysts and cystic neoplasms.
AB  - This article reviews the imaging approach to cystic renal lesions. Imaging
      characteristics of lesions ranging from simple cysts to cystic renal cell
      carcinomas are discussed. The MR appearance of cystic renal masses is described
      and the role of MR imaging in the evaluation of these lesions is discussed.

PMID- 8995125
TI  - MR imaging in the evaluation of small (< or =3.0 cm) renal masses.
AB  - The use of MR imaging in evaluating renal tumors has expanded beyond the
      established utility for patients with renal insufficiency and allergy to
      iodinated contrast. MR imaging is increasingly relied on for the evaluation of
      small renal lesions. The use of gadolinium chelate contrast agents, high
      performance MR systems, and optimized techniques is essential. This article
      details our experience using MR to evaluate small renal tumors and reviews the
      clinical issues pertinent to the management of these lesions.

PMID- 8995126
TI  - Renal MR angiography.
AB  - MR angiography is a noninvasive technique for evaluating blood vessels. Its main
      use in the renal vasculature has been for evaluating the renal arteries for
      stenoses and for diagnosing renal vein thrombosis. Different methods of renal MR
      angiography, including gadolinium-enhanced MR angiography, are described,
      including guidelines for their use. The utility of MR angiography is discussed
      for a variety of clinical indications.

PMID- 8995127
TI  - MR urography.
AB  - Developments of MR imaging of static fluid has led to the emergence of MR
      urography (MRU) as a potential imaging technique of the urinary system. MRU has
      been shown to be highly sensitive in the diagnosis of urinary obstruction,
      defining the severity of dilatation, the site, and in the majority of cases, the
      cause of obstruction. At the current level of resolution, however, MR cannot
      consistently demonstrate nonobstructive or small obstructing calculi.
      Demonstration of perinephric and periuretic edema in obstruction helps in the
      differentiation of acute from nonacute urinary obstruction. MRU has shown
      potential in the work-up of urinary disease for which intravenous urography used
      to be performed, without the hazards of intravenous contrast administration.

PMID- 8995128
TI  - MR imaging of renal function.
AB  - MR imaging has advantages over both computed tomography and nuclear scintigraphy
      for assessing renal function, because it combines high spatial resolution with
      information on perfusion and function. A further advantage is the lack of
      ionizing radiation. Quantitation of flow rate by phase contrast in the renal
      arteries and veins has the potential to provide estimation of renal blood flow,
      which could prove useful in a number of clinical situations, especially for
      studying renal vascular disorders and the effects of treatment, and for assessing
      renal transplants. Evaluation of renal perfusion with MR imaging has become
      feasible with the development of rapid data acquisition techniques, which provide
      adequate temporal resolution to monitor the rapid signal changes during the first
      passage of the contrast agents in the kidneys. More recently, magnetically
      labeling water protons in blood flowing into kidneys has been used to
      noninvasively quantitate regional measurement of cortical and medullary
      perfusion. Other techniques being investigated with MR imaging for assessment of
      renal function include diffusion imaging GFR estimation and blood oxygenation
      level dependent imaging to evaluate intrarenal oxygenation levels.

PMID- 8995129
TI  - The adrenal gland: radiologic-pathologic correlation.
AB  - The adrenal glands are affected by complex physiologic and neoplastic processes.
      Recently described computed tomography densitometry and chemical shift MR imaging
      techniques are useful to distinguish between benign and malignant masses.
      Knowledge of the basic gross pathologic and histologic correlates of adrenal
      disease helps in applying these new imaging methods and in understanding
      established cross-sectional studies.

PMID- 8995130
TI  - Incidentally discovered adrenal masses.
AB  - Incidentally discovered adrenal masses are a common clinical problem. Most of
      these masses lack specific imaging features that enable accurate
      characterization. In this article, the authors describe the imaging findings, as
      well as the roles of various imaging techniques that are currently used to
      evaluate these masses.

PMID- 8995131
TI  - Retroperitoneal MR imaging.
AB  - Although CT is usually the first imaging study used to evaluate for
      retroperitoneal disease, MR imaging is increasingly chosen to further
      characterize lesions. In addition, MR imaging is the ideal modality for
      evaluating the extent of retroperitoneal tumors as well as their relationship to
      adjacent structures and organs. The multiplanar capabilities and soft-tissue
      contrast resolution are significant advantages of MR over CT. This article
      reviews the retroperitoneal anatomy and our current imaging techniques. Disease
      processes that commonly affect the retroperitoneum are discussed along with their
      MR imaging characteristics.

PMID- 8995132
TI  - MR imaging of renal and adrenal masses in children.
AB  - A large variety of benign and malignant masses of the kidneys and adrenal glands
      occur in children. MR imaging is an effective technique for evaluating these
      lesions. It is a particularly useful problem-solving test in patients with
      equivocal ultrasonographic or CT results. The need for sedation of young children
      undergoing MR imaging is a drawback as is its relative insensitivity for
      detecting calcification. Advantages of MR imaging include superior soft-tissue
      contrast, direct acquisition of images in any plane, lack of ionizing radiation,
      and excellent depiction of the abdominal vasculature, bone marrow, and spinal
      canal.

PMID- 8995134
TI  - Applications of molecular epidemiology to head and neck cancer.
AB  - Cancer may be viewed as a genetic disease characterized by the failure of
      cellular mechanisms to maintain genomic integrity. Molecular progression models
      defining genetic damage are being developed for a number of solid tumors
      including head and neck squamous cell carcinoma. Genetic alteration of certain
      classes of genes, the tumor suppressor genes and proto-oncogenes, seem to be
      common events in such models. Host modulation of environmental carcinogens,
      however, also may be an important disease determinant. Interindividual
      differences in susceptibility to the genotoxic effects of environmental
      carcinogens may be genetically determined. With technologic advances in molecular
      genetics, it is now possible to identify specific genetic alterations that occur
      in different stages of neoplasia. Correlation of these genetic alterations with
      susceptibility models for solid tumors has important implications for the field
      of molecular epidemiology.

PMID- 8995135
TI  - Imaging of laryngeal cancer.
AB  - Modern laryngeal imaging with CT scans or MR images provides critical information
      about primary tumor extent and the status of the neck nodes. This information is
      complementary to the physical examination and is essential for treatment planning
      purposes in all but the smallest laryngeal malignancies. This article focuses on
      the modalities available for laryngeal cancer imaging, the strengths and
      weaknesses of those modalities, the imaging anatomy of the larynx, and key
      imaging features of laryngeal cancer. Also briefly discussed are neck nodes, the
      post-treatment appearance of the neck, and the problem of tumor recurrence.

PMID- 8995133
TI  - The etiology and pathogenesis of laryngeal carcinoma.
AB  - Epidemiologic data suggest that the etiology and pathogenesis of laryngeal
      carcinoma are influenced by environmental and lifestyle-related factors, such as
      tobacco use, ethanol consumption, and exposure to toxic substances. In addition,
      dietary factors, irradiation, papilloma virus infection, and laryngopharyngeal
      reflux seem to be significant carcinogenic cofactors. This article presents a
      multi-factorial model of laryngeal mucosal carcinogenesis.

PMID- 8995136
TI  - Surgical management of early supraglottic cancer.
AB  - Surgical management of early supraglottic cancer has evolved over the last half
      of the century from total laryngectomy to inclusion of conservation approaches.
      The development and fundamental principles underlying open supraglottic
      laryngectomy and endoscopic supraglottic resections are reviewed. In doing so, a
      rational approach for the application of these surgical techniques is provided
      for management of both the primary site and the neck.

PMID- 8995137
TI  - Endoscopic surgical management of glottic laryngeal cancer.
AB  - This article recounts the historical development of the endoscopic surgical
      management of stage I and stage II glottic cancer. The indications and surgical
      approach to treating stage I cancer and the rationale for extending the original
      limitations to the endoscopic treatment of highly selected stage II glottic
      cancers is described. The indications, technique, and outcomes of the endoscopic
      treatment of stage II glottic cancer are also presented.

PMID- 8995138
TI  - Open surgical management of early glottic carcinoma.
AB  - Three options exist for the treatment of T1 through T3 glottic carcinomas:
      irradiation, transoral excision (usually with a CO2 laser) and external
      "conservation" laryngeal procedures. Controversy re approximately mains regarding
      the best therapy and, in many cases, is related to the uncertainty of tumor
      subclassifications not being contained in the current American Joint Committee on
      Cancer Union International Contra Cancer system. The evaluation of patients with
      early glottic carcinomas and common approaches to conservation laryngeal surgery
      and defect reconstructions are presented. External "conservation" approaches are
      preferred for T1B, T2B and early T3 glottic carcinomas.

PMID- 8995139
TI  - Management of advanced-stage laryngeal cancer.
AB  - Although the total laryngectomy is still the most reliable and simplest method
      for treating advanced laryngeal carcinoma, the shortcomings of the sequelae of
      the procedure have provided a constant challenge for improvement and change. Two
      alternatives that have shown some success are the Pearson near-total laryngectomy
      and the supracricoid partial laryngectomy with cricohyoidopexy and with
      cricohyoidoepiglottopexy. This article covers the procedural differences between
      these alternatives to the total laryngectomy.

PMID- 8995140
TI  - Organ preservation therapy for advanced-stage laryngeal carcinoma.
AB  - The standard treatment for patients with advanced laryngeal cancer remains total
      laryngectomy. Radiotherapy as a primary treatment modality is a reasonable
      alternative. Surgical salvage by total laryngectomy is an important part of the
      treatment plan when irradiation is used primarily to treat advanced laryngeal
      cancer. The value of induction and concomitant chemotherapy in laryngeal
      preservation protocols remains controversial. The currently accepted role for use
      of chemotherapy outside of research protocols is for palliation of incurable
      laryngeal cancers. The nonsurgical treatment of patients with advanced laryngeal
      cancers requires the coordinated efforts of a team with close patient follow-up
      in order that survival not be compromised.

PMID- 8995141
TI  - Definitive radiation management for carcinoma of the glottic larynx.
AB  - Radiation therapy offers excellent cure rates and preservation of the larynx in
      the majority of early-stage glottic cancers. Outcome may vary because of patient
      , tumor-, and treatment-related variables. Carefully selected advanced lesions
      may also be successfully managed with irradiation. Hyperfractionation and
      combined chemotherapy-radiotherapy protocols seem to be promising strategies for
      the improvement of the therapeutic ratio in treatment of patients with more
      advanced lesions.

PMID- 8995155
TI  - Bilateral cystic adrenal masses in the neonate associated with the incomplete
      form of Beckwith-Wiedemann syndrome.
AB  - We report a case of bilateral multilocular cystic adrenal masses in a neonate who
      demonstrated somatic hypertrophy and macroglossia, which are considered to
      constitute an incomplete form of Beckwith-Wiedemann syndrome (BWS). After
      surgical removal of the masses, histological study revealed benign hemorrhagic
      macrocysts with cortical cytomegaly. There was no evidence of tumor or adrenal
      apoplexia. Although very rare, association of unilateral hemorrhagic adrenal
      macrocysts with BWS has been reported before; this is the first case of bilateral
      benign adrenal macrocysts associated with BWS.

PMID- 8995142
TI  - Radiotherapy for carcinoma of the supraglottis.
AB  - Squamous cell carcinoma of the supraglottic larynx is treated primarily by
      conservation surgery or radiotherapy for early to moderately advanced lesions,
      and total laryngectomy, with or without irradiation, for advanced tumors. This
      article reviews the role of radiotherapy, used alone or in combination with
      surgery, for squamous cell carcinoma of the supraglottic larynx. Treatment
      philosophy, techniques, and results from the University of Florida are
      emphasized.

PMID- 8995157
TI  - The Oddono's sulcus and its relation to the renal "junctional parenchymal defect"
      and the "interrenicular septum".
AB  - The anatomy responsible for the sonographic diagnosis of the renal "junctional
      parenchymal defect" and "interrenicular septum" is caused by perirenal fat along
      a line of incomplete fusion of two primary renal lobes. Studies using CT, MRI and
      cadaver observations are presented. "Oddono's sulcus" is suggested as a name for
      the changes in honor of the author who first described these anatomic findings.

PMID- 8995156
TI  - In utero urinary bladder perforation, urinary ascites, and bilateral contained
      urinomas secondary to posterior urethral valves: clinical and imaging findings.
AB  - We report on a rare in utero appearance of urinary bladder perforation, urinary
      ascites, and bilateral contained urinomas secondary to posterior urethral valves.
      The findings on prenatal sonography, postnatal voiding cystourethrography, and
      magnetic resonance imaging are described.

PMID- 8995159
TI  - CT appearances of involvement of the peritoneum, mesentery and omentum in Wilms'
      tumor.
AB  - BACKGROUND: Peritoneal involvement by Wilms' tumor indicates stage III disease.
      CT is the single preferred modality in determining the extent and staging of
      Wilms' tumor; however, the CT appearances of Wilms' tumor involvement of the
      peritoneum have not been specifically addressed in the literature. OBJECTIVE: The
      objective of this study was to demonstrate the CT manifestations when there is
      involvement of the peritoneum, mesentery and/or omentum in Wilms' tumor.
      MATERIALS AND METHODS: Four cases of Wilms' tumor form the basis of this report.
      They were examined on Elscint CT scanners. RESULTS: Masses ("dropped metastases")
      in the pelvis were present in all four patients. Three patients had masses in the
      mesentery of the small bowel and sigmoid colon. Infiltration of the greater
      omentum was identified in two patients as a mantle of tumor separating bowel from
      the anterior abdominal wall. Ascites was present in two patients. In one patient
      broad-based solid masses of varying sizes were noted on the parietal and on the
      visceral surfaces of the peritoneum, and in a different patient a discrete mass
      was noted in the lesser omentum. CONCLUSION: The peritoneal spaces, recesses,
      ligaments and folds are invisible unless invaded by disease which is well
      demonstrated on CT.

PMID- 8995158
TI  - Urethro-vaso-cutaneous fistula in a 5-year-old child.
AB  - A 5-year-old boy with a 4-year history of urethro-vaso-cutaneous fistula is
      presented. This is the youngest patient reported to have an acquired urethro-vaso
      cutaneous fistula. Fistulography is a convenient method for the demonstration of
      such entities.

PMID- 8995160
TI  - Radiological features of fungal typhlitis complicating acute lymphoblastic
      leukaemia.
AB  - We report the radiological features of fungal typhlitis, a complication of acute
      lymphoblastic leukaemia, in a child. Colonic dilatation, intramural gas and a
      tumour-like filling defect in the caecum were demonstrated on ultrasound and
      contrast enema.

PMID- 8995161
TI  - Aggressive bone destruction in acute megakaryocytic leukemia: a rare
      presentation.
AB  - Acute megakaryocytic leukemia (AMKL) is a rare subtype of acute myeloid leukemia
      which is more common in children. Although the bone changes in leukemia are well
      documented, there are only a few reports of the AMKL subtype. We present an
      exceptional case of a young girl with very aggressive AMKL, who demonstrated
      symmetrical destructive lesions of the long bones characteristic of this disease.
      Lytic lesions of the skull and jaws were also present, and these have not been
      previously described in AMKL.

PMID- 8995162
TI  - Primary unilateral renal lymphoblastic lymphoma.
AB  - A 4-year-old boy presented with a right-sided mass. A lobulated tumour in the
      right flank was felt on palpation, and radiological investigation revealed a
      solid, multinodular intrarenal tumour. On biopsy the tumour was found to be a
      lymphoblastic lymphoma.

PMID- 8995163
TI  - Radiological changes after therapeutic use of surfactant in infants with
      respiratory distress syndrome.
AB  - The aims of this study were to determine the incidence of typical chest
      radiography findings - (1) uniform improvement, (2) asymmetrical improvement, (3)
      no improvement or (4) interstitial emphysema - after therapeutic use of
      surfactant and to analyse clinical course and outcome. Chest radiographs of 138
      infants of very low birth weight treated with surfactant were analysed. Twenty
      eight infants with a diagnosis other than typical respiratory distress syndrome
      (RDS), i. e., sepsis, congenital pneumonia and congenital malformation, were
      excluded. In 110 patients with clinical and radiological evidence of typical RDS
      (median gestational age 28 weeks, median birth weight 1070 g) adequate chest
      radiographs from before and within 72 h after surfactant treatment were
      available. The time of surfactant application ranged between 1 and 12 h after
      birth. The most common finding after surfactant treatment was uniform or
      asymmetrical improvement of pulmonary aeration (80 of 110 patients). Patients
      with uniform clearing had the best long-term outcome. Asymmetrical clearance was
      often localised on the right side or in central regions of the lung, and usually
      disappeared after retreatment with surfactant without clinical significance. In
      11 patients no change in aeration was found and retreatment was absolutely
      ineffective. Development of pulmonary inter- stitial emphysema after surfactant
      treatment was a grave prognostic sign: 73 % of these infants died within the
      first 2 weeks of life compared with 10 % of those with uniform or asymmetrical
      improvement of ventilation.

PMID- 8995164
TI  - Pulmonary perfusion scintigraphy in the evaluation of the severity of
      bronchopulmonary dysplasia.
AB  - OBJECTIVE: The objectives of this study were to analyze the changes in pulmonary
      perfusion in bronchopulmonary dysplasia (BPD) and to assess the advantages of
      this method in evaluating the severity of BPD. PATIENTS AND METHODS: The study
      group was made up of 10 children with BPD, matched with a control group of 12
      children. The criteria for matching were birth weight, gestational age and need
      for ventilation for more than 3 days. Clinical and roentgenographic scoring
      systems were applied on the 21st day of life. At 6 months of corrected age,
      clinical evolutive severity was evaluated and a pulmonary perfusion scintigraphy
      using technetium-99 was performed in each child. The scintigraphic findings were
      classified in five categories ranging from normal to severely affected, depending
      on the degree and localization of perfusion abnormalities. Another score was
      obtained by assigning a value from 1 to 5 to each pulmonary lobe, depending on
      the concentration of the tracer. RESULTS: The study of clinical, roentgenographic
      and evolutive scores always showed higher values in children with BPD, with good
      correlation between methods (P < 0.001). In the BPD group, abnormal lung
      perfusion patterns were more frequent and more severe (P < 0. 05), the lobe
      scoring was higher (P < 0.05), and a lower count rate was found (P < 0.01).
      CONCLUSION: Pulmonary scintigraphy is a useful technique in evaluating the
      severity of BPD.

PMID- 8995165
TI  - MR imaging in Guillain-Barre syndrome.
AB  - MRI in a 5-year-old girl with Guillain-Barre syndrome showed marked enhancement
      of nerve roots in the region of the conus medullaris and cauda equina. This
      enhancement gradually disappeared after high-dose immunoglobulin therapy. This
      characteristic finding of MRI may have diagnostic utility and represent the
      clinical course of the disease.

PMID- 8995167
TI  - Normal MR appearances of the posterior pituitary in central diabetes insipidus
      associated with septo-optic dysplasia.
AB  - Magnetic resonance (MR) imaging of the pituitary in children with central
      diabetes insipidus usually shows absence of the normal high signal within the
      posterior gland. The high signal of the normal posterior pituitary is thought to
      be due to the presence of intra- cellular storage granules of vasopressin. MR
      imaging has been advocated as a useful investigation to aid in the distinction
      between central diabetes insipidus and other causes of thirst and polydipsia. We
      report the case of an infant with central diabetes insipidus in association with
      septo-optic dysplasia in whom MR imaging showed normal appearances of the
      posterior pituitary. The mechanism of central diabetes insipidus in this case may
      be related to a failure of hypothalamic function affecting osmoreception, rather
      than to a deficiency of vasopressin. Normal MR appearances of the pituitary do
      not exclude central diabetes insipidus in infants with midline cerebral
      malformations.

PMID- 8995166
TI  - MR imaging of symptomatic neurocutaneous melanosis in children.
AB  - Neurocutaneous melanosis is a syndrome consisting of cutaneous nevi and
      melanocytosis of the leptomeninges. Over a 5-year period (1989-1994) we evaluated
      with MR imaging the central nervous system of five children with a confirmed
      histologic diagnosis of neurocutaneous melanosis. The children ranged in age from
      7 to 10 years and consisted of two girls and three boys. They all had multiple
      pigmented skin lesions (cutaneous nevi) and presented with seizures, signs of
      raised intracranial pressure, cranial nerve palsies and/or myelopathy. The MR
      studies were performed with T1-weighted, T2-weighted and T1-weighted post
      gadolinium images of the brain in addition to T1-weighted post-gadolinium images
      of the entire spine. The MR findings in all the children consisted of marked,
      diffuse enhancement of thickened leptomeninges surrounding the brain and spinal
      cord which was only demonstrated on the post-gadolinium T1-weighted images and
      mild to moderate hydrocephalus. We present our MR findings and compare these
      findings with other imaging findings in the literature. Our findings represent
      part of a spectrum of imaging abnormalities seen in patients with neurocutaneous
      melanosis.

PMID- 8995169
TI  - Gallbladder polyps in children: a rare condition.
AB  - Although gallbladder polyps are well documented in adults, only three cases in
      children have been reported in the literature. We present two pediatric cases in
      which gallbladder polyps were detected by ultrasound, confirming this as the
      imaging method of choice in diagnosing gallbladder disease.

PMID- 8995168
TI  - Hypothalamic-pituitary vascularization in pituitary stalk transection syndrome:
      is the pituitary stalk really transected? The role of gadolinium-DTPA with spin
      echo T1 imaging and turbo-FLASH technique.
AB  - We examined 14 patients, aged 10-25 years, with idiopathic hypopituitarism. All
      presented an ectopic posterior pituitary at the median eminence with a
      hypoplastic anterior pituitary on magnetic resonance imaging (MRI). Eight
      patients had isolated growth hormone deficit (IGHD) and six had multiple hormone
      deficits (MPHD). Unenhanced MRI showed the pituitary stalk, which was extremely
      thin, in only three patients, while T1-weighted images obtained after intravenous
      injection of gadopentetate dimeglumine (Gd-DTPA) showed a thin pituitary stalk in
      seven patients (six with IGHD and one with MPHD), demonstrating a preserved
      vascular component of the stalk. MRI with Gd-DTPA was more sensitive than
      unenhanced MRI in detecting the pituitary stalk in patients with hypopituitarism
      with an ectopic posterior pituitary: the stalk was demonstrated in 50 % of the
      cases (seven patients), versus 21.4 % (three patients) by unenhanced MRI. The
      dynamic study of the hypothalamo-hypophyseal axis performed with turbo-FLASH
      sequences after bolus injection of Gd-DTPA showed the residual anterior pituitary
      to have arterial enhancement times, which suggests that an arterial system
      compensates for the absent or diminished blood supply from the portal system,
      independent of stalk detection.

PMID- 8995170
TI  - Acute gastric outlet obstruction following the administration of prostaglandin:
      an additional case.
AB  - We present a case of neonatal acute gastric outlet obstruction related to
      prostaglandin-induced gastric foveolar hyperplasia, which developed following
      infusion of prostaglandin E1 (PGE1) for treatment of hypoplastic left heart
      syndrome. Abdominal distension occurred after administration of PGE1 in a
      cumulative dose of 2914 microg/kg. Ultrasonography performed after a cumulative
      dose of 5074 microg/kg had been administered disclosed a lobulated thickening of
      the gastric mucosa with a brush-like appearance composed of alternately echogenic
      and hypoechoic, vertically oriented lines. These ultrasonographic findings
      corresponded to the histological abnormalities of gastric foveolar hyperplasia
      with impacted interfoveolar mucin products and dilated mucosal glands. The
      development of gastric outlet obstruction in our patient, a relatively rare
      manifestation of prostaglandin-induced foveolar hyperplasia, might have been
      related to the unusually high cumulative dose of PGE1.

PMID- 8995171
TI  - Pneumatic dilatation in childhood cardio-achalasia.
AB  - Three boys with achalasia of the cardia were treated with balloon dilatation,
      with relief of obstruction and weight gain in all cases. Symptoms recurred in one
      patient, who then underwent myotomy rather than further dilatation. We recommend
      dilatation as the primary procedure in childhood achalasia.

PMID- 8995172
TI  - Imaging diagnosis of alveolar echinococcosis in young patients.
AB  - We review the imaging findings in seven children with alveolar echinococcosis of
      the liver. Calcification was seen on plain abdominal films in five of seven
      patients (66.6 %); the calcifications were small or coarse with irregular
      margins. Ultrasound was performed in four cases, identifying the lesions in all
      four as small calcifications with or without cysts. Computed tomography (CT) was
      performed in four cases and showed small calcifications, calcifications
      surrounding a cyst, or an aggregate of calcifications. Angiography was performed
      in all seven patients and showed changes of intrahepatic arterial stretching,
      overgrowth of small arteries, and a honeycomb pattern in the capillary phase.
      Venography revealed compression of the inferior vena cava in two patients. Serum
      screening together with ultrasonography and CT are useful for diagnostic imaging
      of alveolar echinococcosis.

PMID- 8995173
TI  - Bony involvement in paracoccidioidomycosis.
AB  - We report a rare case of bony involvement by paracoccidioidomycosis in a 4-year
      old boy. Extremity radiographs show a diffuse permeative pattern of metaphyseal
      bony destruction. Although these findings are nonspecific, they may suggest the
      disease in an appropriate clinical setting. Definitive diagnosis, however,
      depends upon detection of Paracoccidioides braziliensis on laboratory analysis.

PMID- 8995174
TI  - Ultrasonography of nondevelopmental dysplasia of the hips.
AB  - We examined 45 infants with nondevelopmental dysplasia of the hip (non-DDH),
      including congenital deficiency of the femur (CDF) (20 infants), neuromuscular
      syndrome (five infants), skeletal dysplasia (15 infants), and infection (five
      infants), and present the sonographic findings. Dysmorphic proximal femora, coxa
      vara, and abnormal echogenicity of the soft tissue and cartilage are features
      which differentiate patients with non-DDH from those with typical DDH.

PMID- 8995175
TI  - Osteoglophonic dysplasia: appearance and progression of multiple nonossifying
      fibromata.
AB  - The appearance and gradual enlargement of fibrous cortical defects and multiple
      nonossifying fibromata are documented in this report of a 2-year-old boy with a
      very rare skeletal dysplasia known as osteoglophonic dysplasia, characterized by
      multiple and recurrent craniosynostoses, platyspondyly, short tubular bones, and
      epiphyseal dysplasia.

PMID- 8995176
TI  - Metallic stenting of the biliary tree following liver transplant hepatic artery
      thrombosis in an infant.
AB  - We report the placement of intrahepatic metallic, balloon-expandable stents in
      the biliary tree following liver transplantation in a 12-month-old infant who
      developed biliary strictures secondary to hepatic artery thrombosis. The use of
      such stents has not previously been reported following transplantation in an
      infant. Re-transplantation was undertaken 5 months after stenting because of
      chronic rejection and progressive obstructive jaundice.

PMID- 8995177
TI  - Hepatic necrosis masquerading as trauma.
AB  - We report the case of a child who had deterioration of hepatic function 3 days
      after suffering a depressed compound skull fracture with underlying brain
      contusion. An abdominal enhanced CT scan revealed a wedge-shaped region of
      devitalised liver with associated free intraperitoneal fluid, consistent with a
      traumatic lesion but due to necrosis secondary to acetaminophen toxicity.
      Acetaminophen toxicity may occur with therapeutic doses in the presence of an
      ischaemic hepatitis. Any delay in the performance of CT from the time of trauma
      should prompt the consideration of alternative diagnoses.

PMID- 8995178
TI  - Emergency transjugular intrahepatic portosystemic shunt prior to liver
      transplantation.
AB  - Transjugular intrahepatic portosystemic shunt (TIPSS) is a new development in the
      management of severe variceal haemorrhage which has been established in adult
      patients. We have successfully adapted this technique for children and describe
      our initial experience in the case of a 9-year-old boy who presented with acute
      and chronic liver failure and uncontrollable life-threatening bleeding from
      oesophageal and gastric varices, despite intensive medical management including
      sclerotherapy. A 10-mm TIPSS was successfully placed with immediate reduction in
      portal pressure and cessation of variceal bleeding. The patient's condition
      stabilised sufficiently for him to undergo liver transplantation 2 days later, at
      which time the TIPSS was patent.

PMID- 8995179
TI  - Mechanical factors associated with posterior rib fractures: laboratory and case
      studies.
AB  - OBJECTIVE: The objective of this study was to explore the mechanical factors
      associated with posterior rib fractures. MATERIALS AND METHODS: Radiographs were
      reviewed in ten cadavers where rib fractures were produced by opening a median
      sternotomy with a sternal retractor. A second study used CT to evaluate for rib
      fractures following digital sternal depression and anteroposterior bimanual
      thoracic compression in three rabbits. Lastly, two cases of accidental posterior
      rib fractures in children were reviewed. RESULTS: In the cadaver studies, ten rib
      fractures were noted, all at or medial to the costotransverse process
      articulations. In the rabbit study, 13 posterior rib fractures were noted, all
      occurring with excessive posterior levering of the ribs during bimanual
      compression. The accidental posterior rib fractures occurred with severe
      anteroposterior thoracic compression as children were decelerated into a car
      dashboard or struck by a car. CONCLUSION: Posterior rib fractures require
      excessive levering of the posterior ribs at the costotransverse process
      articulation. When these fractures occur in accidental situations, they require
      massive forces that entail similar mechanics to those occurring in abusive
      settings.

PMID- 8995180
TI  - Leiomyomas of the gallbladder and splenic calcifications in an HIV-infected
      child.
AB  - Smooth muscle neoplasms seem to be particularly frequent in children with AIDS,
      and several cases of such lesions, both benign and malignant (leiomyomas and
      leiomyosarcomas), have recently been reported in the literature. We describe here
      the imaging findings in a boy with AIDS who developed two leiomyomas of the
      gallbladder wall as well as calcification of the intraparenchymal splenic
      arteries.

PMID- 8995181
TI  - Radiologic-pathologic conference of Children's Hospital Boston: liver nodules
      after heart transplantation.
AB  - We report the case of a 16-year-old boy who presented 1(1)/2 years after heart
      transplantation with multiple lesions throughout the liver as demonstrated by
      ultrasonography and CT. Results of analyses revealed features diagnostic for post
      transplant lymphoproliferative disorder, which rarely involves the liver.

PMID- 8995182
TI  - Differential expression of HLA-DQA1 alleles associated with promoter
      polymorphism.
AB  - The promoter regions of DQA1 alleles are polymorphic, with some of the nucleotide
      sequence polymorphisms being located within X and Y motifs essential for the
      regulation of HLA class II gene transcription. In the present study, we
      demonstrate that polymorphisms in the promoter regions of three DQA1 alleles
      influence constitutive and inducible transcription of reporter gene constructs in
      epithelial, B-, and T-cell lines. Promoter strength in transient transfection
      assays generally followed a pattern of DQA1(*)03011>DQA1(*)0101>DQA1(*)05011, and
      was not affected by the endogenous HLA haplotype of the recipient cells. TNFalpha
      significantly activated the DQA1(*)05011 promoter, but had little effect on the
      DQA1(*)03011 promoter. Mutagenesis of the X and Y motifs of DQA1(*)03011 and
      DQA1(*)05011 demonstrated that nucleotide sequence polymorphisms in the Y element
      had the greatest effect on the promoter strength and differential TNFalpha
      inducibility. The finding that alleles of the DQA1 gene differ in promoter
      strength and responsiveness to TNFalpha suggests a mechanism for the association
      of certain alleles of this gene with susceptibility to autoimmune disease.

PMID- 8995184
TI  - A yeast artificial chromosome contig spanning the mouse immunoglobulin kappa
      light chain locus.
AB  - A single contig spanning the entire mouse immunoglobulin kappa light chain (Igk)
      locus on chromosome 6 has been established using yeast and bacterial artificial
      chromosome clones. Detailed mapping of the Igk locus indicates that a member of
      the Igk-V2 gene family, located about 3.5 megabases upstream of the Igk-J-C
      complex, is the most distal functional Igk-V gene. Sequence analyses of Igk-V
      genes and anonymous DNA segments provide indications for internal duplications at
      the 5' end of the Igk-V locus and identify the likely origin of Igk-V orphon gene
      clusters located elsewhere in the mouse genome.

PMID- 8995183
TI  - Identification of new mamu-DRB alleles using DGGE and direct sequencing.
AB  - Rhesus macaques represent important animal models for biomedical research. The
      ability to identify macaque major histocompatibility complex (Mhc) alleles is
      crucial for fully understanding these models of autoimmune and infectious
      disease. Here we describe a rapid and unambiguous way to distinguish DRB alleles
      in the rhesus macaque using the polymerase chain reaction, denaturing gradient
      gel electrophoresis (DGGE), and direct sequencing. The highly variable second
      exon of Mamu-DRB alleles was amplified using generic DRB primers and alleles were
      separated by DGGE. DNA was then reamplified from plugs removed from the gel and
      alleles were determined using fluorescent-based sequencing. Validity of this
      typing procedure was confirmed by identification of all DRB alleles for three
      macaques previously characterized by cloning and sequencing techniques.
      Importantly, our analysis revealed DRB alleles not previously identified in the
      three reference animals. Using this technique, we identified 40 alleles in
      fifteen unrelated macaques. On the basis of phylogenetic tree analyses, 14 new
      DRB alleles were assigned to 10 different Mhc-DRB lineages. Interestingly, two of
      the new DRB6 lineages had previously been identified in prosimians and pigtailed
      macaques. Whereas traditional DRB typing methods provide limited information, our
      new technique provides a simple and relatively rapid way of identifying DRB
      alleles for tissue typing, determining individual identification and studies of
      disease association and susceptibility. This new technique should also contribute
      to ongoing studies of Mhc function and evolution in many different species of
      nonhuman primates.

PMID- 8995186
TI  - Allele-specific expression of the mouse B-cell surface protein CD72 on T cells.
AB  - CD72 is a 45 000 Mr mouse B-cell surface glycoprotein involved in B-cell
      proliferation and differentiation. Expression of mouse CD72 is thought to be
      restricted to the B-cell lineage. We recently demonstrated that the monoclonal
      antibodies K10.6 and B9.689, previously defined as recognizing the mouse
      lymphocyte alloantigens Ly-19.2 and Ly-32.2, respectively, recognize specific
      alleles of CD72. Early studies using antibody-mediated cytotoxicity assays
      demonstrated that K10.6 and B9.689 react with B cells, several T-cell lines, and
      a subset of peripheral T cells. These findings led us to consider the possibility
      that CD72 might also be expressed on a subset of T cells. In this report we
      demonstrate that CD72 is constitutively expressed on a fraction of peripheral T
      cells isolated from strains of mice expressing the CD72(b) allele, but not the
      CD72(a) or CD72(c) alleles. Three days after activating T cells with concanavalin
      A or plate-bound CD3-specific mAb, CD72 is expressed on a larger fraction of
      peripheral T cells as well as a fraction of thymocytes from mouse strains
      expressing the CD72(b) allele. CD72 is expressed on both the CD4(+) and CD8(+)
      thymocyte and peripheral T-cell subsets. No CD72 expression is detected on
      activated thymocytes or peripheral T cells from mouse strains expressing the
      CD72(a) or CD72(c) alleles. Expression of CD72(b) on peripheral T cells was
      confirmed by northern blot analysis demonstrating CD72 mRNA expression. These
      results demonstrate that CD72 expression is not restricted to B lineage cells in
      mouse strains expressing the CD72(b) allele; instead, a population of T lineage
      cells in these mice also expresses CD72.

PMID- 8995185
TI  - Polymorphisms in the TNF gene cluster and MHC serotypes in the West of Scotland.
AB  - We examined the distribution of polymorphic elements within the tumor necrosis
      factor (TNF) gene cluster in 105 unrelated individuals and determined their
      relationship to class I and class II major histocompatibility complex (MHC)
      antigens, and to the highly polymorphic microsatellites TNFa and TNFb. The data
      demonstrate the contribution of elements within the TNF cluster to two extended
      haplotypes which are recognized to straddle the MHC. The A1.B8.DR3 haplotype
      appears to contain the TNF alleles TNFa2, TNFb3, LT.Nco-1.B*1, and TNF-308.2,
      while the A3.B7.DR2 haplotype is associated with the TNF alleles TNFa11, TNFb6,
      TNFc1, LT.Nco-1.B*2, LT.AspH1.1, TNF-308.1, and TNFe1. The presence of other
      extended associations which covered smaller parts of the MHC was also suggested.
      In most cases, the associations described here were in keeping with previously
      described extended haplotypes which dominate the structure of the MHC, but these
      did not always match completely. Taken together, these data suggest that the
      structure of the TNF locus is well integrated into the rest of the MHC but that
      important ethnic differences may exist.

PMID- 8995187
TI  - Analysis of VH gene diversity in rainbow trout (Oncorhynchus mykiss): both
      nonsynonymous and synonymous nucleotide changes are more frequent in CDRs than in
      FRs.
AB  - Forty-six immunoglobulin VH gene sequences of rainbow trout were compiled to
      analyze the extent of variations and the frequency of nucleotide changes in CDRs
      and FRs. The results show that the frequency of nonsynonymous (amino acid
      replacing) changes (Ka) are on average 4.9 times higher in complementarity
      determining regions (CDRs) than in FRs, thus contributing more diversity in CDRs.
      Unexpectedly, however, the frequency of synonymous (silent) changes (Ks) show the
      same tendency: it was 5.3 times higher in CDRs than in framework regions (FRs).
      The distribution of Ks/Ka ratios of each comparison shows no segregation between
      CDRs and FRs. The same analysis applied to five germline VH genes of Heterodontus
      francisci shows the same result as was found with the rainbow trout. In contrast,
      the results from mouse data show that, while the CDR/FR ratio for Ka is much
      higher (7.4), the CDR/FR ratio for Ks is only slightly higher (1.8). The
      distribution of Ks/Ka ratios in mouse indicates clear segregation between CDRs
      and FRs. This suggests that CDR germline diversity is largely generated by gene
      conversion in VHs of lower vertebrates such as rainbow trout or shark. This
      mechanism might be advantageous to lower vertebrates in generating V gene
      diversity faster than other mechanisms such as point mutation and selection.

PMID- 8995189
TI  - Cloning and chromosomal localization of ncf4, the mouse homologue of p40-phox.

PMID- 8995188
TI  - Allelic and interlocus comparison of the PERB11 multigene family in the MHC.
AB  - The major histocompatibility complex (MHC) contains at least a hundred genes over
      4 megabases of DNA. Within the MHC there are several new multigene families which
      have been recently described. PERB11 is a multigene family which occurs over the
      class I and central region of the MHC. Two members of the family have been shown
      to be functional and share domains with members of the supergene family including
      HLA class I, FcRn, and Zn-alpha2-glycoprotein molecules. The two functional
      members are contained within an area of the MHC which has been associated with
      increased susceptibility to autoimmune diseases such as insulin-dependent
      diabetes mellitus and also rapid progression to AIDS following HIV-1 infection.
      Intralocus and interlocus differences between PERB11.1 and PERB11.2 include: (1)
      several nucleotide substitutions leading to amino acid changes; (2) presence and
      absence of potential glycosylation sites; (3) insertions and deletions leading to
      a frame shift resulting in diversity at the amino acid level and an early
      termination signal. There are ten different alleles of PERB11.1 including one
      allele which contains a frame shift in the transmembrane region causing a
      putative truncated molecule lacking the cytoplasmic tail. The significance of
      this polymorphism in disease associations is under investigation. The most
      divergent domain is the transmembrane region when PERB11.1 and PERB11.2 are
      compared. The results suggest that these two molecules may have different
      functions.

PMID- 8995190
TI  - Mouse class II transactivator: cDNA sequence and amino acid comparison with the
      human class II transactivator.

PMID- 8995191
TI  - Identification of a predominant sequence variant of the T-cell receptor TCRBC1
      gene.

PMID- 8995192
TI  - Functional expression of the NKB1 killer cell inhibitory receptors on agammadelta
      CTL clone.

PMID- 8995194
TI  - Conservation of a polymorphic microsatellite at orthologous positions in the
      human and mouse CD5 gene promoter.

PMID- 8995193
TI  - A distinctive peptide binding motif for HLA-DRB1*0407, an HLA-DR4 subtype not
      associated with rheumatoid arthritis.

PMID- 8995195
TI  - Expression of the gap junction protein connexin43 in the subependymal layer and
      the rostral migratory stream of the mouse: evidence for an inverse correlation
      between intensity of connexin43 expression and cell proliferation activity.
AB  - Connexins constitute the channel-forming proteins of gap junctions. Gap junctions
      are considered to be involved in the regulation of cell proliferation. To verify
      this hypothesis for connexin43, the most abundant connexin in brain tissue, we
      have analyzed the expression of this gap junction protein in the subependymal
      layer and the rostral migratory stream of the murine telencephalon. These regions
      reveal high proliferative activity, even during postnatal stages and in
      adulthood. Proliferating cells were labeled in vivo by means of the
      bromodeoxyuridine method and were later processed for double immunocytochemistry
      by using an antibody to connexin43. The relationship between connexin43
      expression and cell proliferation was also determined in primary cell cultures of
      olfactory bulbs from newborn mice. The intercellular coupling efficiency of
      cultured bulbar cells was also analyzed by dye-transfer experiments in
      combination with the bromodeoxyuridine technique. In the rostral migratory
      stream, connexin43 was upregulated during postnatal development, coinciding with
      a decrease of BrdU incorporation. Comparative quantification of the intensity of
      connexin43 immunoreactivity by confocal laser microscopy and of BrdU-labeled
      cells showed a clear reverse correlation between connexin43 expression and cell
      proliferation in the rostral migratory stream during postnatal development. A
      marked reverse correlation of both parameters was also observed in primary cell
      cultures from olfactory bulbs at day 6 after seeding.

PMID- 8995196
TI  - The shape of synaptic ribbons in the rat pineal gland.
AB  - Under the transmission electron microscope, synaptic ribbons (SRs) of the
      mammalian pineal gland appear as rod-like organelles. Their three-dimensional
      structure is not precisely known. In the present study, pineal SRs were
      investigated using serial sections obtained from rats killed at noon and
      midnight. The shape of the SRs was reconstructed based on SR profile length and
      the number of sections in which the profiles were contained. The results obtained
      show that SRs are basically flat plate-like structures with polymorphic lateral
      edges. Reconstructions of SRs revealed that they had average dimensions of
      300x150x35 nm and were 19.3% larger at night than at day; the difference in SR
      size points to perhaps major differences in synaptic function between day and
      night.

PMID- 8995197
TI  - Remodeling of pineal epithelium in the fetal rat as delineated by
      immunohistochemistry of laminin and cadherin.
AB  - Epithelial remodeling in the rat pineal during fetal development was
      immunohistochemically analyzed by using antibodies for laminin and cadherin as
      molecular markers of basal lamina and intercellular junctions, respectively. The
      proliferation and differentiation of pinealocytes were also investigated in
      relation to the advance of epithelial remodeling. The pineal anlage of embryonic
      day 16 is completely covered by basal lamina immunolabeled for laminin. After
      embryonic day 17, local dissolution of the basal lamina occurs on the epithelial
      folds, which develop predominantly in the rostral pineal wall. Some pineal cells
      migrate through these interruptions and form cellular aggregations outside the
      basal lamina. Cadherin immunostaining reveals focal dissolution of intercellular
      junctions in epithelial regions protruding into the pineal lumen. Dissolution of
      the basal lamina and intercellular junctions accompanied by cellular migration
      into the stromal tissue or into the pineal lumen continues until birth. The
      distribution of mitotic cells immunolabeled for BrdU is homogeneous throughout
      the organ during the fetal period, whereas that of differentiating pinealocytes
      immunoreactive for synaptophysin shows striking regional heterogeneity in close
      correlation with the remodeling of the pineal epithelium. The migrating cell
      populations located either outside the basal lamina or inside the pineal lumen
      are more liable to become synaptophysin-positive than the rest of the epithelium.
      These results suggest that epithelial remodeling in the fetal pineal is induced,
      at least in part, by epithelial infolding and that this remodeling promotes the
      differentiation of pinealocytes.

PMID- 8995198
TI  - Immunoreactive excitatory amino acids in the parietal eye of lizards, a
      comparison with the pineal organ and retina.
AB  - The fine structure of the organ and the localization of the excitatory amino
      acids glutamate and aspartate were studied in the parietal eye of lizards by
      postembedding immunoelectron microscopy. The parietal eye contains cone
      photoreceptor cells, secondary neurons, and ependymal and lens cells. The
      photoreceptors form long inner and outer segments, some of them being paired as
      "twin-photoreceptors" by zonulae adherentes. Perikarya of neurons bear sensory
      cilia (containing 9x2+0 pairs of tubules) extending into the intercellular space.
      No neurohormonal terminals are present in the parietal eye. A higher
      immunoreactivity to glutamate than to aspartate is found in the photoreceptors
      and in the secondary neurons of the parietal eye. Glutamate immunogold labeling
      is more intense in the axonal processes of photoreceptors and neurons and in most
      of the nerve fibers of the parietal nerve running to the brain stem. Weak
      aspartate and glutamate immunoreactivity can be detected in the ependymal and
      lens cells. A similar distribution of immunoreactive amino acids is found in the
      photoreceptors, secondary neurons, and ependymal glial elements of the pineal
      organ, and retina of the lateral eye of the same animals. Immunoreactive
      glutamate accumulates in the axons of photoreceptors and secondary neurons of the
      parietal eye suggesting that this excitatory amino acid acts as a synaptic
      mediator in the neural efferentation of the organ. Thus, the efferent light
      conducting pathway of the parietal organ is similar to that of the pineal organ
      and lateral eye retina. As the Mullerian cells of the retina, the ependymal and
      lens cells of the parietal eye and the ependymal-glial cells of the pineal organ
      may play a role in the metabolism and/or elimination of excitatory amino acids
      released by photoreceptors.

PMID- 8995199
TI  - Reissner's fibre promotes neuronal aggregation and influences neuritic outgrowth
      in vitro.
AB  - Reissner's fibre is the condensed form of glycoproteins secreted by the
      subcommissural organ; it extends through the central canal to the caudal end of
      the spinal cord. The effect of Reissner's fibre was assessed on dissociated
      embryonic chick cortical neuronal cells grown in chemically defined medium, by
      using two cell culture systems: (1) low-density cultures, in which neuronal cells
      remained evenly distributed; (2) high-density cultures, in which neuronal cells
      aggregated, displaying prominent neuritic outgrowth. Reissner's fibre, when added
      to low-density cultures, induced neuronal aggregation and neuritic outgrowth but
      this effect was restricted to an area centred around Reissner's fibre. Reissner's
      fibre, when added to high-density cultures, potentiated cell aggregation.
      Antibodies inhibiting the neural cell adhesion molecule or N-cadherin, and
      soluble Reissner's fibre material (reported previously to have anti-aggregative
      activity), did not prevent the aggregative activity induced by Reissner's fibre.
      Neuronal cells showed a similar reaction pattern when heparin or Reissner's fibre
      was added to the culture. These results suggest that the subcommissural
      organ/Reissner's fibre complex has multifunctional activities and may modulate
      cell-cell interactions during the development of the central nervous system.

PMID- 8995200
TI  - Characterization of pars intermedia connections in amphibians by biocytin tract
      tracing and immunofluorescence aided by confocal microscopy.
AB  - Biocytin, recently introduced in neuroanatomical studies, was used as a
      retrograde tract tracer in combination with immunofluorescence in order to
      analyse the neurochemical characters of some central neuronal projections to the
      pars intermedia in two amphibian species, the anuran Rana esculenta and the
      urodele Triturus carnifex. After biocytin insertions in the pars intermedia,
      neurons became retrogradely labelled in the suprachiasmatic hypothalamus and the
      locus coeruleus of the brainstem in both species. Some scattered biocytin
      labelled neurons were observed in the preoptic area. Moreover, working on the
      same sections, immunofluorescence revealed a number of codistributions and, in
      some cases, colocalization in the same neurons of biocytin labellings and
      immunopositivity for (1) tyrosine hydroxylase in the suprachiasmatic hypothalamus
      and the locus coeruleus of Rana and Triturus, (2) gamma-aminobutyric acid in the
      suprachiasmatic hypothalamus of Rana and Triturus and (3) neuropeptide Y in the
      suprachiasmatic hypothalamus of Rana. The specificity of such colocalizations was
      fully confirmed using dual-channel confocal laser scanning microscopy analysis.

PMID- 8995201
TI  - Distribution of vasotocin- and mesotocin-like immunoreactivities in the brain of
      typhlonectes compressicauda (Amphibia, gymnophiona): further assessment of
      primitive and derived traits of amphibian neuropeptidergic systems.
AB  - To further assess primitive and derived conditions, we have studied the
      vasotocinergic (AVT) and mesotocinergic (MST) systems by immmunohistochemistry in
      the brain of Typhlonectes compressicauda. This species belongs to a separate
      order of amphibians which differs in several morphological and behavioral aspects
      from anurans and urodeles which have been studied previously. Nevertheless, the
      vasotocinergic and mesotocinergic systems of T. compressicauda are largely
      comparable to those of other amphibians. Apart from a well-developed hypothalamo
      hypophyseal system, extrahypothalamic AVT-and MST-immunoreactive groups of cells
      and extensive networks of fibers were found. A major difference, however, is that
      neuropeptidergic cells in the caudal hypothalamus and the midbrain tegmentum of
      T. compressicauda contain MST, whereas those in corresponding locations contain
      AVT in anurans and urodeles. This suggests that certain neuropeptidergic cell
      groups in the gymnophionan brain have switched from AVT to MST gene expression,
      and, thereby, offers a new view on the functional significance of these
      neuropeptidergic systems.

PMID- 8995202
TI  - Denervation-induced changes in perineuronal plexuses in the major pelvic ganglion
      of the rat: immunohistochemistry for vasoactive intestinal polypeptide and
      tyrosine hydroxylase and histochemistry for NADPH-diaphorase.
AB  - To characterize further the injury response of autonomic ganglia, we have
      examined the effect of chronic denervation on perineuronal plexuses that are
      immunoreactive for vasoactive intestinal polypeptide (VIP) and tyrosine
      hydroxylase (TH) or that stain for nicotinamide adenine dinucleotide phosphate
      (NADPH) in the rat major pelvic ganglion, and their relationship to an identified
      sub-population of neurons in the ganglion (the penile neurons). Penile neurons
      contain VIP and NADPH diaphorase (NADPH-D) but lack TH. VIP-immunoreactive (VIP
      IR) and TH-IR perineuronal plexuses (baskets) are rare in the rat major pelvic
      ganglion and those present are not associated with penile neurons. A small
      increase in VIP-IR baskets occurs 2 weeks after proximal interruption of the
      pelvic nerve, but TH-IR baskets increase five-fold. The emergent VIP-IR and TH-IR
      baskets enclose TH-negative neurons, none of which are penile ganglion cells.
      These changes remain up to 4 weeks after denervation. Interrupting the pelvic
      nerve nearer the margin of the major pelvic ganglion results in a rapid, more
      dramatic increase in VIP-IR, in cell bodies and beaded fibers, than that seen
      with the more proximal lesion. About 27% of neurons in the ventral pole of the
      ganglion are enveloped by NADPH-D perineuronal baskets. The incidence of NADPH-D
      baskets falls to less than 1% after acute interruption of the pelvic and
      hypogastric nerves, but their frequency returns to control levels in chronically
      denervated ganglia. The rapid, vigorous changes in peptide (VIP) fibers after the
      pelvic nerve is cut close to the major pelvic ganglion may be attributable to the
      interruption of axons of postganglionic neurons and to preganglionic nerve
      fibers, whereas the slowly developing changes in VIP-IR and TH-IR fibers after
      more proximal lesions may represent the more modest effects of true
      decentralization. The source and significance of the VIP-IR, TH-IR, and NADPH-D
      baskets that appear in chronically denervated ganglia remain unclear.

PMID- 8995203
TI  - Endocytosis of gastrin in cancer cells expressing gastrin/CCK-B receptor.
AB  - Endocytosis of gastrin was studied in a number of gastrin-receptor-expressing
      cell lines by confocal laser scanning microscopy (CLSM) with the aid of a
      biologically active fluorescent derivative, rhodamine green heptagastrin. Rapid
      clustering (within 4-7 min) and internalization of fluorescent ligand upon
      binding at room temperature and 37 degrees C were observed in the rat pancreatic
      acinar carcinoma cell line AR42J, human gastric carcinomas AGS-P and SIIA, human
      colon carcinomas HCT116 and HT29, and in NIH/3T3 cells transfected with human and
      rat gastrin/cholecystokinin-B receptor cDNA. Internalization was inhibited by
      hypertonic medium. Fluorescent heptagastrin and transferrin colocalized in the
      same endocytic vesicles at different stages of internalization suggesting that
      endocytosis occurred predominantly through a clathrin-dependent mechanism. At 37
      degrees C partial colocalization with the lysosomal marker neutral red was
      detected by CLSM, implying that internalized gastrin accumulated in the
      lysosomes. Immunoelectron microscopy studies with antibodies against gastrin
      revealed the presence of the internalized hormone in multivesicular vesicles and
      endosomes. Almost no hormone was detected in lysosomes with the antibodies to
      gastrin, suggesting that the degradation of the peptide is rapid in those
      vesicles. Continuous accumulation of fluorescent label was observed by CLSM in
      the presence of the protein synthesis inhibitor cycloheximide, suggesting that
      the gastrin receptor is recycled back to the cell membrane after hormone delivery
      to intracellular compartments. An estimated average recycling time for the
      receptor molecules was 1 h in NIH/3T3 cells.

PMID- 8995204
TI  - Distribution and subcellular localization of a lysosome-associated protein in
      human genital organs.
AB  - The tissue distribution, preferentially in the human male genital system, and the
      subcellular localization of the lysosome-associated membrane protein 2 (lamp 2)
      was studied immunohistochemically using a mouse monoclonal antibody, 2D5. Strong
      immunoreactivity was present in the tubular system of the kidney, in acinar cells
      of salivary glands and pancreas, prostate, mammary glands, placenta and in
      cutaneous sweat glands. Moderate immunoreactivity was observed in cerebral
      neuronal cells, epidermal cells, testis, epididymis, seminal vesicle and
      endometrium. Very low immunoreactivity was found in liver. In some of the tissues
      mentioned, the distribution pattern of immunoreactivity is smooth and
      homogeneous, while in others it is granular and concentrated in the supra- or
      perinuclear cytoplasm. The subcellular distribution was studied on
      ultracryosections and on pre-embedding-processed chopper sections of human
      prostate. In the latter gland, the protein is not restricted to epithelium, but
      is also present in stromal cells. Ultrastructurally, the immunoreactivity in
      secretory cells was localized in electron-translucent vacuoles and granules,
      including the secretory granules. A close association with cell membranes was not
      generally the case. Only part of the immunoreactive material was linked to the
      apical plasma membrane pointing to a biosynthesis independent from an association
      step with the apical plasma membrane. As shown by immunoelectron microscopy and
      Western blotting, a high amount of lamp 2 is secreted and is found in so-called
      prostasomes. The findings indicate that in the human prostate most of the
      membrane-bound lamp 2 is released from the secretory cells, presumably in an
      apocrine fashion.

PMID- 8995205
TI  - Differential distribution of the mitochondrial heat-shock protein 60 in rat
      gastrointestinal tract.
AB  - Immunohistochemical studies on various parts of the rat gastrointestinal tract by
      means of an antibody against the mitochondrial chaperonin, heat-shock protein 60
      (hsp60), has revealed a cell-specific distribution pattern. The active form of
      hsp60 is a heptameric complex that is involved in the import and refolding of
      nuclear-encoded proteins destined for the mitochondrial matrix. This chaperonin
      is detectable in highly replicating cells, e. g., keratinizing cells of the
      esophagus and short-living epithelial cells of the intestine. In the stomach,
      some of the oxyntic cells contain hsp60-positive mitochondria lying near
      intracellular canaliculi. Neuronal cells of the enteric nervous system present
      intense positive staining for hsp60 in some areas. All other non-epithelial cells
      of the digestive tract show weak or no hsp60 immunoreactivity. The presence of
      hsp60 in mitochondria seems to reflect two different forms of mitochondrial
      renewal: (1) total reformation of mitochondria and their content after mitotic
      division and (2) regeneration of these organelles following high activity, e. g.,
      ATP synthesis.

PMID- 8995206
TI  - Occurrence of enzymes of free radical metabolism suggests the possible cytotoxic
      capacity of the transitional epithelium of the human ureter.
AB  - Three enzymes, viz., tartrate-resistant acid phosphatase (TRAP), nitric oxide
      synthase I (NOS-I), and superoxide dismutase (SOD), involved in the production
      and metabolism of free radicals or radical equivalents, were demonstrated by
      immunocytochemistry in the urothelium of the ureters of six patients of various
      ages. Two of these enzymes (TRAP and NOS-I) were colocalized in the most apical
      and lateral border of the superficial cells of the urothelium. In contrast, SOD
      showed a patchy or granular distribution within the supranuclear region of these
      cells. Intra- and subepithelial macrophages exhibited a weak TRAP, but no NOS-I
      or SOD, immune reaction. On the basis of the immunocytochemical findings,
      arguments in favor of a cytotoxic function of the superficial cells of the human
      urothelium are presented.

PMID- 8995207
TI  - Autotransplantation of the spleen in the rat: donor leukocytes of the splenic
      fragment survive implantation to migrate and proliferate in the host.
AB  - Loss of the spleen may lead to fatal bacterial infections. As a preventive
      procedure splenic autotransplantation has been performed in humans and
      experimental animals. However, there is still controversy about the protective
      function of this procedure, partly because the process of regeneration after
      implantation of splenic tissue is not fully understood. In the present study the
      question was addressed of whether, in contrast to the current view, leukocytes
      survive the phase of necrosis after implantation of splenic fragments. Rats
      (LEW.7A; host) received splenic fragments of a congenic rat strain (LEW.7B;
      donor). These fragments first underwent almost complete necrosis, then
      regenerated, finally developing the typical splenic compartments. Twenty weeks
      after implantation, leukocytes which had survived the implantation procedure (7B
      positive; donor) and those which had migrated from the host into the splenic
      implant (7B negative; host) were differentiated using a specific monoclonal
      antibody (anti-7B) and immunohistology. In addition, the rats received 5-bromo-2
      deoxyuridine (BrdU) 1 day before the splenic autotransplant and several lymphoid
      and non-lymphoid organs were removed. This thymidine analogue is incorporated in
      proliferating cells during the S-phase of the cell cycle and can be revealed by
      immunohistology. The present study demonstrates that macrophages and B and T
      lymphocytes survive the implantation procedure and are found in the organ
      compartments of the splenic autotransplant. The lymphocytes proliferate and
      migrate into lymphoid and non-lymphoid organs. Both the number of surviving
      leukocytes in the splenic autotransplants and the number of donor lymphocytes
      found in various host organs varied considerably between single animals. Thus,
      not only fibroblasts but also macrophages and lymphocytes survive the avascular
      implantation of splenic fragments. The surviving leukocyte subsets may be
      involved in the regulation of the regeneration of the different splenic
      compartments, so increasing their numbers may finally lead to an improvement in
      the function of splenic autotransplants in the clinical situation.

PMID- 8995208
TI  - Cytokeratins in the liver of the sea lamprey (Petromyzon marinus) before and
      after metamorphosis.
AB  - Cytokeratins of the liver were examined during the lamprey life cycle. This organ
      transforms, at metamorphosis, from a ductal larval structure to an aductal adult
      organ lacking the biliary passageways. Specifically, the relationship between
      liver morphology and cytokeratins 7, 18, and 19, and several unidentified
      cytokeratins was compared in larvae, transformers, and adults. Immunofluorescence
      staining showed that spatiotemporal cytokeratin distributions are cell-type
      specific among hepatocytes, bile-duct cells, and gallbladder cells. In the larva,
      cytokeratins 7 and 19, and other unknown cytokeratins occur diffusely in the
      hepatocyte cytoplasm and prominently in the apices of hepatocytes near a bile
      canaliculus, so that collectively these cytokeratins form a pericanalicular ring.
      At mid-metamorphosis, the ring disappears, and cytokeratins are located
      predominantly in the periphery of bile-duct cells. In the adult, cytokeratin 19
      has a sexually dimorphic distribution. Electrophoretic separations of
      cytoskeletal extracts of larval and adult livers have revealed larval
      cytokeratins 46, 49, 58, and 63.5, and adult male cytokeratins 46, 48, 49, 52.5,
      58, 63.5, 64.5, 65, and 66. Immunoblotting has shown that certain cytokeratins
      are each related to at least two mammalian cytokeratins. We suggest that lamprey
      specific liver cytokeratins exist, and that the metamorphosing liver can be used
      as a model for studying the relationship between cytokeratin organization and
      cell function.

PMID- 8995209
TI  - Cytokeratin-filament expression in epithelial and non-epithelial tissues of the
      common carp (Cyprinus carpio).
AB  - Cytokeratin expression in mammals is generally restricted to epithelial cells and
      has been utilized to differentiate epithelial from nonepithelial tissues in these
      species. Since cytokeratins have been shown to be highly conserved during
      vertebrate evolution, the objective of the present study has been to ascertain
      the expression pattern of cytokeratins in tissues of the common carp (Cyprinus
      carpio). A panel of 10 anti-human cytokeratin antibodies was evaluated using a
      streptavidin-biotin-peroxidase complex detection system. Tissues were fixed in
      10% neutral-buffered formalin, 100% ethanol or methacarn. Only formalin-fixed
      tissues were pre-digested with trypsin prior to immunostaining. Formalin-fixed
      tissues generally resulted in a less intense, more diffuse staining pattern with
      considerable background compared with ethanol and methacarn and was therefore the
      least desirable fixative. The diverse staining pattern observed with the various
      antibodies used in this study was consistent with previous findings in other
      teleosts. The results confirm that cytokeratin expression in teleosts is
      fundamentally different from that in mammals and therefore should be used as a
      method to differentiate epithelial cell types in these species only with
      discretion.

PMID- 8995210
TI  - Formation of a whorl-like autophagosome by Golgi apparatus engulfing a ribosome
      containing vacuole in corpora allata of the cockroach Diploptera punctata.
AB  - Previously, we showed that synchronous autophagy occurred in the corpora allata
      during the declining phase of juvenile hormone synthesis in mated adult females
      of the cockroach Diploptera punctata. At the onset of this process, conspicuous
      whorl-like autophagosomes were often observed. Each consisted of a ribosome
      containing vacuole at the center surrounded by about eight layers of double
      membranes. Labeling the cis-Golgi cisternae with hot osmium and histochemical
      detection of thiamine pyrophosphatase in the trans-Golgi cisternae were used to
      trace the autophagic process. We conclude that the membranes surrounding the
      whorl-like autophagosome are derived from the entire Golgi apparatus with its cis
      cisternae forming the outermost layer and the trans-cisternae the innermost
      layer. The engulfing process is initiated through direct contact between trans
      cisternae of the Golgi apparatus and the isolation membrane of the ribosome
      containing vacuole. Formation of a whorl-like autophagosome appears to be a
      highly regulated process specific to ribosome-containing vacuoles since it occurs
      only on day 5 and the Golgi apparatus does not recognize membranes of other types
      of autophagic vesicles or of functional organelles. This novel behavior of the
      Golgi apparatus in the corpora allata should play an important role in the long
      term inhibition of juvenile hormone synthesis (e.g., during gestation) since it
      results in the depletion of cellular machinery for juvenile hormone synthesis.

PMID- 8995211
TI  - Development of adult thoracic leg muscles during metamorphosis of the hawk moth
      Manduca sexta.
AB  - During metamorphosis, the larval thoracic legs of the hawk moth Manduca sexta are
      replaced by a new set of adult legs. The larval leg motoneurons persist to
      innervate new adult muscles, and the motor terminals remain within the developing
      adult legs. Here we describe the fate of the larval leg muscles and the origin of
      new muscles within the adult legs. During the larval instars, large and small
      nuclei proliferate within leg muscle fibers. Near the end of the larval stage a
      subset of the small nuclei undergo a wave of proliferation, as indicated by the
      incorporation of 5-bromodeoxyuridine, whereas other nuclei die. However, none of
      the larval leg muscles fibers persist to serve as templates for adult muscle
      formation, and there was no evidence for persistence of larval myonuclei.
      Migrating myoblasts that are born within aggregate to form adult muscle anlagen
      at specific production sites within the developing imaginal legs. Intense nuclear
      proliferation occurs within the anlagen during the early pupal stage, followed by
      muscle fiber formation and striation. We conclude that adult leg muscles form
      mainly, if not exclusively, from migrating myoblasts that without the involvement
      of larval elements.

PMID- 8995212
TI  - Acetylcholine and histamine are transmitter candidates in identifiable
      mechanosensitive neurons of the spider Cupiennius salei: an immunocytochemical
      study.
AB  - Histochemical and indirect immunocytochemical techniques were used to search for
      neuroactive substances and transmitter candidates in identified sensory neurons
      of two types of cuticular mechanoreceptors in the spider Cupiennius salei Keys.:
      (1) in lyriform slit-sense organ VS-3 (comprising 7-8 cuticular slits each
      innervated by 2 bipolar neurons), and (2) in tactile hairs (each supplied by 3
      bipolar sensory cells). All neurons are mechanosensitive. A polyclonal antibody
      against choline acetyltransferase (ChAT) strongly labeled all cell bodies and
      afferent fibers of both mechanoreceptor types. Western blot analysis using the
      same antibody against samples of spider sensory hypodermis and against samples
      from the central nervous system demonstrated a clear band at 65 kDa,
      corresponding to the molecular mass of ChAT in insects. Moreover, staining for
      acetylcholine esterase (AChE) revealed AChE activity in one neuron of each
      mechanoreceptor type. Incubation with a polyclonal antibody against histamine
      clearly labeled one neuron in each set of sensilla, whereas activity in the
      remaining one or two cells was near background. All mechanoreceptor preparations
      treated with a polyclonal antiserum against serotonin tested negative, whereas
      sections through the central nervous system of the same spiders were clearly
      labeled for serotonin. The presence of ChAT-like immunoreactivity and AChE
      implicates acetylcholine as a transmitter candidate in the two mechanoreceptive
      organs. We assume that histamine serves as a mechanosensory co-transmitter in the
      central nervous system and may also act at peripheral synapses that exist in
      these sensilla.

PMID- 8995213
TI  - Organization of the antennal motor system in the sphinx moth Manduca sexta.
AB  - The antennae of the sphinx moth Manduca sexta are multimodal sense organs, each
      comprising three segments: scape, pedicel, and flagellum. Each antenna is moved
      by two systems of muscles, one controlling the movement of the scape and
      consisting of five muscles situated in the head capsule (extrinsic muscles), and
      the other system located within the scape (intrinsic muscles) and consisting of
      four muscles that move the pedicel. At least seven motoneurons innervate the
      extrinsic muscles, and at least five motoneurons innervate the intrinsic muscles.
      The dendritic fields of the antennal motoneurons overlap one another extensively
      and are located in the neuropil of the antennal mechanosensory and motor center.
      The density of motoneuronal arborizations is greatest in the lateral part of this
      neuropil region and decreases more medially. None of the motoneurons exhibits a
      contralateral projection. The cell bodies of motoneurons innervating the
      extrinsic muscles are distributed throughout an arching band of neuronal somata
      dorsal and dorsolateral to the neuropil of the antennal mechanosensory and motor
      center, whereas the cell bodies of motoneurons innervating the intrinsic muscles
      reside mainly among the neuronal somata situated dorsolateral to that neuropil.

PMID- 8995214
TI  - The role of sequestration in G protein-coupled receptor resensitization.
      Regulation of beta2-adrenergic receptor dephosphorylation by vesicular
      acidification.
AB  - G protein-coupled receptor kinases phosphorylate the agonist occupied
      conformation of G protein-coupled receptors in the plasma membrane, leading to
      their desensitization. Receptor resensitization requires receptor
      dephosphorylation, a process which is mediated by a plasma and vesicular membrane
      associated form of PP-2A. We present evidence that, like receptor
      phosphorylation, receptor dephosphorylation is tightly regulated, requiring a
      specific receptor conformation induced by vesicular acidification. In vitro,
      spontaneous dephosphorylation of phosphorylated receptors is observed only at
      acidic pH. Furthermore, in intact cells upon agonist stimulation, phosphorylated
      receptors traffic from the plasma membrane to vesicles where they become
      physically associated with the phosphatase and dephosphorylated. Treatment of
      cells with NH4Cl, which disrupts the acidic pH found in endosomal vesicles,
      blocks association of the receptors with the phosphatase and blocks receptor
      dephosphorylation. These findings suggest that a conformational change in the
      receptor induced by acidification of the endosomal vesicles is the key
      determinant regulating receptor dephosphorylation and resensitization.

PMID- 8995215
TI  - Colipase stabilizes the lid domain of pancreatic triglyceride lipase.
AB  - Pancreatic lipase is characterized by increased activity against water-insoluble
      substrates and by dependence on another protein, colipase, for binding to the
      substrate interface. In most models of pancreatic lipase activity, colipase
      functions to anchor lipase on the substrate interface. Recent studies of the x
      ray crystal structure of the complex between colipase and lipase suggest another
      function for colipase in maintaining the active conformation of lipase. We tested
      this hypothesis by introducing mutations into colipase at position 15, a residue
      that contacts the lid domain lipase in the open conformation. Multiple mutant
      colipases were expressed and shown to have decreased activity. To further
      investigate the function of the interaction between Glu15 of colipase and lipase,
      we examined one mutant, E15R, in detail. This mutant had 175-fold less activity
      compared with wild-type colipase. Although E15R had decreased activity, it was as
      effective as wild-type lipase in anchoring lipase to mixed emulsions of bile salt
      and tributyrin. The importance of the interaction with the lid domain was tested
      by determining the activity of E15R with lid deletion mutants of lipase. E15R was
      as active as wild-type colipase with these mutant lipases. These results indicate
      that Glu15 is critical for activity of the colipase-lipase complex at an
      interface and that colipase has a function in lipolysis in addition to anchoring
      lipase to an interface. We propose that this function is to stabilize the lid
      domain of lipase in the open conformation, thereby facilitating lipolysis.

PMID- 8995216
TI  - Geranylgeranylated rho small GTPase(s) are essential for the degradation of
      p27Kip1 and facilitate the progression from G1 to S phase in growth-stimulated
      rat FRTL-5 cells.
AB  - Cyclin-dependent kinase (Cdk) enzymes are activated for entry into the S phase of
      the cell cycle. Elimination of Cdk inhibitor protein p27Kip1 during the G1 to S
      phase is required for the activation process. An inhibitor of 3-hydroxy-3
      methylglutaryl-CoA reductase prevents its elimination and leads to G1 arrest.
      Mevalonate and its metabolite, geranylgeranyl pyrophosphate, but not farnesyl
      pyrophosphate, restore the inhibitory effect of pravastatin on the degradation of
      p27 and allow Cdk2 activation. By the addition of geranylgeranyl pyrophosphate,
      Rho small GTPase(s) are geranylgeranylated and translocated to membranes during
      G1/S progression. The restoring effect of geranylgeranyl pyrophosphate is
      abolished with botulinum C3 exoenzyme, which specifically inactivates Rho. These
      results indicate (i) among mevalonate metabolites, geranylgeranyl pyrophosphate
      is absolutely required for the elimination of p27 followed by Cdk2 activation;
      (ii) geranylgeranylated Rho small GTPase(s) promote the degradation of p27 during
      G1/S transition in FRTL-5 cells.

PMID- 8995218
TI  - Evidence for a catalytic role of zinc in protein farnesyltransferase.
      Spectroscopy of Co2+-farnesyltransferase indicates metal coordination of the
      substrate thiolate.
AB  - Protein farnesyltransferase (FTase) is a zinc metalloenzyme that catalyzes the
      addition of a farnesyl isoprenoid to a conserved cysteine in peptide or protein
      substrates. We have substituted the essential Zn2+ in FTase with Co2+ to
      investigate the function of the metal polyhedron using optical absorption
      spectroscopy. The catalytic activity of FTase is unchanged by the substitution of
      cobalt for zinc. The absorption spectrum of Co2+-FTase displays a thiolate-Co2+
      charge transfer band (epsilon320 = 1030 M(-1) cm(-1)) consistent with the
      coordination of one cysteine side chain and also ligand field bands (epsilon560 =
      140 M(-1) cm(-1)) indicative of a pentacoordinate or distorted tetrahedral metal
      geometry. Most importantly, the ligand-metal charge transfer band displays an
      increased intensity (epsilon320 = 1830 M(-1) cm(-1)) in the ternary complex of
      FTase x isoprenoid x peptide substrate indicative of the formation of a second
      Co2+-thiolate bond as cobalt coordinates the thiolate of the peptide substrate. A
      similar increase in the ligand-metal charge transfer band in a product complex
      indicates that the sulfur atom of the farnesylated peptide also coordinates the
      metal. Transient kinetics demonstrate that thiolate-cobalt metal coordination
      also occurs in an active FTase x FPP x peptide substrate complex and that the
      rate constant for the chemical step is 17 s(-1). These data provide evidence that
      the zinc ion plays an important catalytic role in FTase, most likely by
      activation of the cysteine thiol of the protein substrate for nucleophilic attack
      on the isoprenoid.

PMID- 8995217
TI  - LSP1 is the major substrate for mitogen-activated protein kinase-activated
      protein kinase 2 in human neutrophils.
AB  - In intact cells, mitogen-activated protein kinase-activated protein (MAPKAP)
      kinase 2 is rapidly activated by various cytokines, stresses, and chemotactic
      factors. The small heat shock protein p27 has been shown to be a substrate for
      MAPKAP kinase 2. Recently, we identified a novel substrate, designated p60, for
      MAPKAP kinase 2 in human neutrophils (Zu, Y.-L., Ai, Y., Gilchrist, A., Labadia,
      M. E., Sha'afi, R. I., and Huang, C.-K. (1996) Blood 87, 5287-5296). To further
      understand the signaling pathway of MAPKAP kinase 2, we have purified p60 from a
      heat-treated neutrophil lysate by DEAE-cellulose chromatography and SDS
      polyacrylamide gel electrophoresis. Microsequencing of five peptides derived from
      purified p60 indicates that p60 is lymphocyte-specific protein 1 (LSP1).
      Furthermore antibodies specific for human and mouse LSP1 react with human and
      mouse p60. The sequence of human LSP1 indicates two serine residues at positions
      204 and 252 as potential phosphorylation sites. The amino acid sequences
      surrounding these two sites are in agreement with the consensus sequence (Xaa-Xaa
      Hyd-Xaa-Arg-Xaa-Xaa-Ser-Xaa-Xaa) for phosphorylation by MAPKAP kinase 2. Both
      serine residues in human LSP1 and the corresponding conserved serine residues in
      mouse LSP1 are in the basic C-terminal F-actin binding domain. Various fusion
      proteins of wild type and truncated mouse LSP1 with glutathione S-transferase
      were tested for their capacity to be phosphorylated by MAPKAP kinase 2. The
      results indicate that LSP1 is a substrate for MAPKAP kinase 2 in vitro and that
      the phosphorylation sites are located in the basic C-terminal domain of LSP1.
      Because both the small heat shock proteins and LSP1 are F-actin binding proteins,
      these results suggest a role for MAPKAP kinase 2 in the regulation of
      cytoskeletal structure or function.

PMID- 8995219
TI  - Stimulation of matrix metalloproteinase production by recombinant extracellular
      matrix metalloproteinase inducer from transfected Chinese hamster ovary cells.
AB  - Many of the tumor-associated matrix metalloproteinases that are implicated in
      metastasis are produced by stromal fibroblasts within or surrounding the tumor in
      response to stimulation by factors produced by tumor cells. In this study we
      transfected Chinese hamster ovary cells with putative cDNA for human
      extracellular matrix metalloproteinase inducer (EMMPRIN), a transmembrane
      glycoprotein that is attached to the surface of many types of malignant human
      tumor cells and that has previously been implicated in stimulation of matrix
      metalloproteinase production in fibroblasts. We show that these transfected cells
      synthesize EMMPRIN that is extensively post-translationally processed; this
      recombinant EMMPRIN stimulates human fibroblast production of interstitial
      collagenase, stromelysin-1, and gelatinase A (72-kDa type IV collagenase). We
      propose that EMMPRIN regulates matrix metalloproteinase production during tumor
      invasion and other processes involving tissue remodeling.

PMID- 8995220
TI  - Converting tissue type plasminogen activator into a zymogen. Important role of
      Lys156.
AB  - In stark contrast to most other members of the chymotrypsin family of serine
      proteases, tissue type plasminogen activator (t-PA) is not synthesized and
      secreted as a true zymogen. Instead, single-chain t-PA exhibits very significant
      catalytic activity. Consequently, the zymogenicity, or ratio of the catalytic
      efficiencies of the mature, two-chain enzyme and the single-chain precursor, is
      only 3-9 for t-PA. Both we and others have previously proposed that Lys156 may
      contribute directly to this exceptional property of t-PA by forming interactions
      that selectively stabilize the active conformation of the single-chain enzyme. To
      test this hypothesis we created variants of t-PA in which Lys156 was replaced by
      a tyrosine residue. As predicted, the K156Y mutation selectively suppressed the
      activity of the single-chain enzyme and thereby substantially enhanced the
      enzyme's zymogenicity. In addition, however, this mutation produced a very
      dramatic increase in the ability of single-chain t-PA to discriminate among
      distinct fibrin co-factors. Compared with wild type t-PA, one of the variants
      characterized in this study, t-PA/R15E,K156Y, possessed substantially enhanced
      response to and selectivity among fibrin co-factors, resistance to inhibition by
      plasminogen activator inhibitor type 1, and significantly increased zymogenicity.
      The combination of these properties, and the maintenance of full activity in the
      presence of fibrin, suggest that the R15E,K156Y mutations may extend the
      therapeutic range of t-PA.

PMID- 8995221
TI  - Conditions of forming protein complexes with GroEL can influence the mechanism of
      chaperonin-assisted refolding.
AB  - The interaction of GroEL with urea-unfolded dihydrofolate reductase (DHFR) has
      been studied in the presence of DHFR substrates by investigating the ability of
      GroES to release enzyme under conditions where a stable GroES-GroEL-DHFR ternary
      complex can be formed. In these circumstances, GroES could only partially
      discharge the DHFR if ADP was present in the solution and approximately half of
      the DHFR remained bound on the chaperonin. This bound DHFR could be rescued by
      addition of ATP and KCl into the refolding mixture. The stable ternary complex
      did not show any significant protection of bound DHFR against proteolysis by
      Proteinase K. These results are in contrast to those observed with the GroEL-DHFR
      complex formed by thermal inactivation of DHFR at 45 degrees C in which GroES
      addition leads to partial protection of bound DHFR. Thus, the method of
      presentation influences the properties of the bound intermediates. It is
      suggested that the ability of GroES to bind on the same side of the GroEL double
      toroid as the target protein and displace it into the central cavity depends on
      the way the protein-substrate is presented to the GroEL molecule. Therefore, the
      compact folding intermediate formed by thermal unfolding can be protected against
      proteolysis after GroES binds to form a ternary complex. In addition, structural
      changes within GroEL induced by the experimental conditions may contribute to
      differences in the properties of the complexes. The more open urea-unfolded DHFR
      binds on the surface of chaperonin and can be displaced into solution by the
      tighter binding GroES molecule. It is suggested that the state of the unfolded
      protein when it is presented to GroEL determines the detailed mechanism of its
      assisted refolding. It follows that individual proteins, having characteristic
      folding intermediates, can have different detailed mechanisms of chaperonin
      assisted folding.

PMID- 8995222
TI  - Identification of a novel Ca2+-dependent, phosphatidylethanolamine-hydrolyzing
      phospholipase D in yeast bearing a disruption in PLD1.
AB  - We have previously reported the identification and partial characterization of a
      gene encoding a phospholipase D activity (PLD1) in the yeast, Saccharomyces
      cerevisiae. Here we report the existence of a second phospholipase D activity,
      designated PLD2, in yeast cells bearing disruption at the PLD1 locus. PLD2 is a
      Ca2+-dependent enzyme which preferentially utilizes phosphatidylethanolamine over
      phosphatidylcholine as a substrate. In contrast to PLD1, the activity of PLD2 is
      insensitive to phosphatidylinositol 4,5-bisphosphate, and the enzyme is incapable
      of catalyzing the transphosphatidylation reaction with short chain alcohols as
      acceptors. Subcellular fractionation shows that PLD2 localizes mainly to the
      cytosol, but could also be detected in the particulate fraction. Thus, the
      biochemical properties of PLD2 appear to be substantially different from those of
      PLD1. PLD2 activity is significantly and transiently elevated upon exit of wild
      type yeast cells from stationary phase, suggesting that it may play a role in the
      initiation of mitotic cell division in yeast. In view of the significantly
      different properties of PLD1 and PLD2, and because the yeast genome contains PLD1
      as the sole member of the recently defined PLD gene family, it may be concluded
      that PLD2 is structurally unrelated to PLD1. Thus, the novel PLD2 activity
      described herein is likely to represent the first identified member of a new PLD
      gene family.

PMID- 8995223
TI  - Growth hormone-induced signal tranduction depends on an intact ubiquitin system.
AB  - The growth hormone receptor (GHR) is a ubiquitinated cell surface protein. Ligand
      binding and receptor dimerization activate the cytosolic kinase Jak2. This event
      initiates signal transduction via STAT proteins. Expression of GHR in a Chinese
      hamster ovary (CHO) cell line, which exhibits a temperature-sensitive defect in
      ubiquitin conjugation (CHO-ts20), as well as in wild type cells (CHO-E36) has
      shown that endocytosis of the receptor requires an intact ubiquitin conjugation
      system (Strous G. J., van Kerkhof, P., Govers, R., Ciechanover A., and Schwartz,
      A. L. (1996) EMBO J. 15, 3806-3812). We have now examined the requirement for
      ubiquitin conjugation in growth factor-mediated signal transduction. In CHO-E36
      and in CHO-ts20 cells at the permissive temperature, STAT proteins were activated
      in a growth factor-dependent fashion. However, no activation of STAT proteins was
      observed at the nonpermissive temperature in CHO-ts20 cells. Neither tyrosine
      phosphorylation of GHR nor of Jak2 was inhibited at the nonpermissive
      temperature. When tyrosine phosphorylation was inhibited following treatment with
      staurosporin, ubiquitination of the receptor proceeded normally. Furthermore,
      mutation of GHR phenylalanine-327, which prevents GHR endocytosis, inhibited
      receptor ubiquitination but allowed normal Jak/STAT-mediated signal transduction.
      Thus, these data provide evidence that the ubiquitin conjugation system is
      involved in the Jak/STAT signaling pathway, be it not at the initial stage(s) of
      Jak2 activity.

PMID- 8995224
TI  - Channel formation by a neurotoxic prion protein fragment.
AB  - Prions cause neurodegenerative disease in animals and humans. Recently it was
      shown that a 21-residue fragment of the prion protein (106-126) could be toxic to
      cultured neurons. We report here that this peptide forms ion-permeable channels
      in planar lipid bilayer membranes. These channels are freely permeable to common
      physiological ions, and their formation is significantly enhanced by "aging"
      and/or low pH. We suggest that channel formation is the cytotoxic mechanism of
      action of amyloidogenic peptides found in prion-related encephalopathies and
      other amyloidoses. The channels reported here are large enough and nonselective
      enough to mediate cell death through discharge of cellular membrane potential,
      changes in ionic homeostasis, and specifically, influx of calcium, perhaps
      triggering apoptosis.

PMID- 8995226
TI  - DUB-2 is a member of a novel family of cytokine-inducible deubiquitinating
      enzymes.
AB  - Cytokines regulate cell growth by inducing the expression of specific target
      genes. We have recently identified a cytokine-inducible, immediate-early gene,
      DUB-1, that encodes a deubiquitinating enzyme with growth regulatory activity. In
      the current study, we have isolated a highly related gene, DUB-2, that is induced
      by interleukin-2. The DUB-2 mRNA was induced in T cells as an immediate-early
      gene and was rapidly down-regulated. Like DUB-1, the DUB-2 protein had
      deubiquitinating activity in vitro. When a conserved cysteine residue of DUB-2,
      required for ubiquitin-specific thiol protease activity, was mutated to serine
      (C60S), deubiquitinating activity was abolished. DUB-1 and DUB-2 proteins are
      highly related throughout their primary amino acid sequence except for a
      hypervariable region at their COOH terminus. Moreover, the DUB genes co-localize
      to a region of mouse chromosome 7, suggesting that they arose by a tandem
      duplication of an ancestral DUB gene. Additional DUB genes co-localize to this
      region, suggesting a larger family of cytokine-inducible DUB enzymes. We propose
      that different cytokines induce specific DUB genes. Each induced DUB enzyme
      thereby regulates the degradation or the ubiquitination state of an unknown
      growth regulatory factor, resulting in a cytokine-specific growth response.

PMID- 8995225
TI  - Identification of Rox3 as a component of mediator and RNA polymerase II
      holoenzyme.
AB  - Yeast Rox3 protein, implicated by genetic evidence in both negative and positive
      transcriptional regulation, is identified as a mediator subunit by peptide
      sequence determination and is shown to copurify and co-immunoprecipitate with RNA
      polymerase II holoenzyme.

PMID- 8995227
TI  - Binding of amyloid beta protein to the 20 S proteasome.
AB  - Neurodegenerative disorders of aging are characterized by the intraneuronal
      accumulation of ubiquitin conjugates into tangles and inclusions. Ubiquitin
      conjugates are degraded by cellular particles known as proteasomes. We have
      previously shown that amyloid beta protein (Abeta) inhibits proteasomal activity
      and thereby blocks ubiquitin conjugate degradation. In the present studies, we
      found that Abeta binds the 20 S proteasome and forms a proteasome-Abeta complex.
      The complex was detected by Western blot with anti-Abeta antibodies. Using a 1.4
      nm Nanogold-labeled Abeta, we visualized proteasome-Abeta complexes by scanning
      transmission electron microscopy (STEM). Analysis of the side-on oriented
      proteasome-Abeta complexes revealed a single gold particle, corresponding to one
      gold-labeled Abeta, in the middle portion of the proteasome. On end-on views of
      proteasome-Abeta complexes, gold was detected within the area delimited by the
      proteasome circular projection. Both STEM views are consistent with Abeta
      localization inside the proteasome along the peptide channel. Direct interaction
      of Abeta with the inner catalytic compartment of the proteasome may explain the
      generation of ubiquitin-containing lesions in Alzheimer's disease and other
      neurodegenerative disorders. In addition, detection of Nanogold-labeled peptide
      inside the 20 S eukaryotic proteasome suggests that conformational constraints
      for protein degradation in eukaryotic proteasomes are different from those in
      archaebacteria proteasomes.

PMID- 8995228
TI  - Collagen-stimulated activation of Syk but not c-Src is severely compromised in
      human platelets lacking membrane glycoprotein VI.
AB  - Activation of circulating platelets by subendothelial collagen is an essential
      event in vascular hemostasis. In human platelets, two membrane glycoprotein (GP)
      abnormalities, integrin alpha2 beta1 deficiency and GPVI deficiency, have been
      reported to result in severe hyporesponsiveness to fibrillar collagen. Although
      it has been well established that integrin alpha2 beta1, also known as the GPIa
      IIa complex, functions as a primary platelet adhesion receptor for collagen, the
      mechanism by which GPVI contributes to collagen-platelet interaction has been ill
      defined to date. However, our recent observation that GPVI cross-linking couples
      to cyclic AMP-insensitive activation of c-Src and Syk tyrosine kinases suggested
      a potential role for GPVI in regulating protein-tyrosine phosphorylation by
      collagen (Ichinohe, T., Takayama, H., Ezumi, Y., Yanagi, S., Yamamura, H., and
      Okuma, M. (1995) J. Biol. Chem. 270, 28029-28036). To further investigate this
      hypothesis, here we examined the collagen-induced protein-tyrosine
      phosphorylation in GPVI-deficient platelets expressing normal amounts of alpha2
      beta1. In response to collagen, these platelets exhibited alpha2 beta1-dependent
      c-Src activation accompanied by tyrosine phosphorylation of several substrates
      including cortactin. In contrast, severe defects were observed in collagen
      stimulated Syk activation and tyrosine phosphorylation of phospholipase C-gamma2,
      Vav, and focal adhesion kinase, implicating a specific requirement of GPVI for
      recruiting these molecules to signaling cascades evoked by collagen-platelet
      interaction.

PMID- 8995229
TI  - A two-stage mechanism for the reductive unfolding of disulfide-containing
      proteins.
AB  - Reductive unfolding of disulfide-containing proteins can be experimentally
      dissected into two distinct stages. In the presence of denaturant and thiol
      catalyst, native proteins unfold by reshuffling their native disulfides and
      convert to a mixture of scrambled structures. Subsequent reduction of the
      disulfide bonds of scrambled proteins requires only mild concentration of
      reductant (0.2-0.5 mM reduced dithiothreitol) and undergoes intermediates that
      consist of highly heterogeneous disulfide isomers. These properties have been
      characterized with three cystine-containing proteins, namely hirudin, tick
      anticoagulant peptide (TAP), and bovine ribonuclease A. In the cases of hirudin
      and TAP, most intermediates observed during the oxidative folding were found to
      exist along the pathway of reductive unfolding as well.

PMID- 8995230
TI  - The catalytic domain of protein kinase C-delta in reciprocal delta and epsilon
      chimeras mediates phorbol ester-induced macrophage differentiation of mouse
      promyelocytes.
AB  - The overexpression of protein kinase C-delta (PKC-delta), but not PKC-epsilon,
      enables the mouse myeloid cell line 32D to differentiate into macrophages when
      treated with phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA).
      To determine the domain of PKC-delta that is responsible for this isotype
      specific function, cDNAs that encode reciprocal chimeras of PKC-delta and 
      epsilon (PKC-delta epsilon and PKC-epsilon delta) were constructed by exchanging
      regulatory and kinase domains using polymerase chain reaction technology. Both
      chimeras were stably expressed in 32D cells using the pLTR expression vector and
      displayed protein kinase activity upon TPA treatment. TPA treatment of L epsilon
      delta, cells that overexpressed the PKC-epsilon delta chimera, induced a
      dramatically increased cell volume, surface adherence, surface expression of Mac
      1 and Mac-3, lysozyme production, and phagocytosis. These are the characteristics
      of the macrophage phenotype found in TPA-treated 32D cells that overexpressed PKC
      delta. In contrast, little effect was seen in L delta epsilon, 32D cells that
      overexpressed PKC-delta epsilon, with or without TPA treatment. A PKC inhibitor
      directed toward the catalytic domain of PKC, GF109203X, and a selective inhibitor
      of PKC-delta, Rottlerin, blocked the TPA-induced differentiation of PKC-epsilon
      delta-overexpressing 32D cells. These results demonstrate that the catalytic
      domain of PKC-delta contains the primary determinants for its activity in phorbol
      ester-induced macrophage differentiation.

PMID- 8995231
TI  - Occlusion of RNA polymerase by oligomerization of DnaA protein over the dnaA
      promoter of Escherichia coli.
AB  - DnaA protein, the initiator protein for initiation of Escherichia coli
      chromosomal replication, has been shown to repress its own expression from two
      dnaA promoters, 1P and 2P. The sequence-specific binding of DnaA protein to the
      DnaA box, located between the two promoters, results in subsequent
      oligomerization of DnaA protein. Upon increasing the concentration of DnaA
      protein, the oligomerization proceeds to both dnaA promoters from the DnaA box
      and inhibits RNA polymerase binding to both promoters. This results in the
      repression of transcription, suggesting that the extent of oligomerization of
      DnaA proteins over two dnaA promoters contributes to the autoregulation of
      expression of the dnaA gene. When the two dnaA promoters were bound and repressed
      by DnaA protein, the interaction of RNA polymerase with IciA protein, which is a
      specific inhibitor of initiation of in vitro E. coli chromosomal replication,
      appeared to dissociate the oligomerized DnaA proteins from the 1P promoter and
      allowed RNA polymerase to be loaded for its transcription.

PMID- 8995232
TI  - Apolipoprotein E inhibits platelet aggregation through the L-arginine:nitric
      oxide pathway. Implications for vascular disease.
AB  - We have previously reported that plasma apolipoprotein (apo) E-containing high
      density lipoprotein particles have a potent anti-platelet action, apparently by
      occupying saturable binding sites in the cell surface. Here we show that purified
      apoE (10-50 microg/ml), complexed with phospholipid vesicles
      (dimyristoylphosphatidylcholine, DMPC), suppresses platelet aggregation induced
      by ADP, epinephrine, or collagen. This effect was not due to sequestration of
      cholesterol from platelet membranes; apoE x DMPC chemically modified with
      cyclohexanedione (cyclohexanedione-apoE x DMPC) did not inhibit aggregation but
      nevertheless removed similar amounts of cholesterol as untreated complexes, about
      2% during the aggregation period. Rather we found that apoE influenced
      intracellular platelet signaling. Thus, apoE x DMPC markedly increased cGMP in
      ADP-stimulated platelets which correlated with the resulting inhibition of
      aggregation (r = 0.85; p < 0.01, n = 10), whereas cyclohexanedione-apoE x DMPC
      vesicles had no effect. One important cellular mechanism for up-regulation of
      cGMP is through stimulation of nitric oxide (NO) synthase, the NO generated by
      conversion of L-arginine to L-citrulline, binds to and activates guanylate
      cyclase. This signal transduction pathway was implicated by the finding that NO
      synthase inhibitors of distinct structural and functional types all reversed the
      anti-platelet action of apoE, whereas a selective inhibitor of soluble guanylate
      cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (100 nM), had a similar
      reversing action. Direct confirmation that apoE stimulates NO synthase was
      obtained by use of L-[3H]arginine; platelets pretreated with apoE x DMPC produced
      markedly more L-[3H]citrulline (0.71 +/- 0.1 pmol/h/10(9) platelets) than
      controls (0.18 +/- 0.03; p < 0.05). In addition, hemoglobin which avidly binds NO
      also suppressed the anti-aggregatory effect, indicating that apoE stimulated
      sufficient production of NO by platelets for extracellular release to occur. We
      conclude that apoE inhibits platelet aggregation through the L-arginine:NO signal
      transduction pathway.

PMID- 8995233
TI  - IkappaB alpha overexpression in human breast carcinoma MCF7 cells inhibits
      nuclear factor-kappaB activation but not tumor necrosis factor-alpha-induced
      apoptosis.
AB  - Nuclear factor-kappaB (NF-kappaB) is one of major component induced by tumor
      necrosis factor-alpha (TNF), and its role in the signaling of TNF-induced cell
      death remains controversial. In order to delineate whether the involvement of NF
      kappaB activation is required for triggering of the apoptotic signal of TNF, we
      inhibited the nuclear translocation of this transcription factor in TNF-sensitive
      MCF7 cells by introducing a human MAD-3 mutant cDNA coding for a mutated IkappaB
      alpha that is resistant to both phosphorylation and proteolytic degradation and
      that behaves as a potent dominant negative IkappaB alpha protein. Our results
      demonstrated that the mutated IkappaB alpha was stably expressed in the
      transfected MCF7 cells and blocked the TNF-induced NF-kappaB nuclear
      translocation. Indeed, TNF treatment of these cells induced the proteolysis of
      only the endogenous IkappaB alpha but not the mutated IkappaB alpha. The nuclear
      NF-kappaB released from the endogenous IkappaB alpha within 30 min of TNF
      treatment was rapidly inhibited by the mutated IkappaB alpha. There was no
      significant difference either in cell viability or in the kinetics of cell death
      between control cells and the mutated IkappaB alpha transfected cells.
      Furthermore, electron microscopic analysis showed that the cell death induced by
      TNF in both control and mutated IkappaB alpha transfected cells was apoptotic.
      The inhibition of NF-kappaB translocation in mutated IkappaB alpha-transfected
      cells persisted throughout the same time course that apoptosis was occurring. Our
      data provide direct evidence that the inhibition of NF-kappaB did not alter TNF
      induced apoptosis in MCF7 cells and support the view that TNF-mediated apoptosis
      is NF-kappaB independent.

PMID- 8995234
TI  - Hck is activated by opsonized zymosan and A23187 in distinct subcellular
      fractions of human granulocytes.
AB  - Regulation of neutrophil responses is known to involve tyrosine phosphorylation.
      Hck, a major neutrophil protein-tyrosine kinase, becomes expressed during
      differentiation of human promyelocytic NB4 cells into neutrophil-like cells. Hck
      is mainly localized in a secretory granule-enriched cell fraction, but it is also
      present in a granule-free membrane fraction and the cytosol. Hck is rapidly and
      transiently activated upon stimulation of differentiated NB4 cells or human
      neutrophils with serum-opsonized zymosan or the calcium ionophore A23187, but not
      by phorbol 12-myristate 13-acetate. In NB4 cells, Hck is also weakly activated by
      fMet-Leu-Phe. Cell fractionation showed that opsonized zymosan and A23187 induce
      Hck activation in distinct subcellular fractions. Both stimuli activate Hck in
      the secretory granule-enriched fraction, but only A23187 activates the kinase in
      the granule-free membrane fraction. Our results suggest that Hck might regulate
      early signal transduction events induced by opsonized zymosan and A23187, and
      that the different subcellular fractions of Hck might serve discrete functions,
      one of which could be regulation of the degranulation response.

PMID- 8995235
TI  - 1,25-dihydroxyvitamin D3 inhibits Osteocalcin expression in mouse through an
      indirect mechanism.
AB  - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), a key regulator of mineral metabolism,
      regulates the expression of several genes that are expressed in osteoblasts. In
      particular, in rat and human osteoblasts, 1,25-(OH)2D3 increases the expression
      of Osteocalcin by interacting, through a hormone-receptor complex, with a vitamin
      D-responsive element present in the promoter of the genes. Here we show that in
      mouse, 1,25-(OH)2D3 inhibits the expression of both osteocalcin genes, OG1 and
      OG2. This inhibition was observed in primary osteoblast cultures and in the whole
      animal. From sequence inspection, DNA transfection experiments, and DNA binding
      assays, we could not identify a functional vitamin D-responsive element in the
      promoter of OG2 or in the first 3.3 kilobases of the OG1 promoter. However, we
      show that 1,25-(OH)2D3 treatment of primary osteoblasts abolishes the binding of
      OSF2, an osteoblast-specific activator of transcription that binds to OSE2, a
      critical osteoblast-specific cis-acting element present in OG1 and OG2 promoters.
      Consistent with these DNA binding data, a mutation in OSE2 in the OG2 promoter
      abrogated the inhibitory effect of 1,25-(OH)2D3 treatment on this promoter
      activity. This study illustrates that 1,25-(OH)2D3 can play different roles in
      the expression of the same gene in various species and indicates that this
      regulation in mouse occurs through an indirect mechanism, 1,25-(OH)2D3 acting on
      a gene genetically located upstream of Osteocalcin.

PMID- 8995236
TI  - Mycobacterium smegmatis phosphoinositols-glyceroarabinomannans. Structure and
      localization of alkali-labile and alkali-stable phosphoinositides.
AB  - Lipoarabinomannans from fast growing Mycobacterium sp., namely AraLAMs, stimulate
      the early events of macrophage activation. The immunological activities of all of
      these AraLAMs drastically decrease with the loss of the mild alkali groups, which
      were believed to be restricted to the fatty acid residues from the phosphatidyl
      myo-inositol anchor. This report reveals the presence and the structure of mild
      alkali-labile phosphoinositide units linked via the phosphate to the C-5 of the
      beta-D-Araf in the AraLAMs of Mycobacterium smegmatis, a fast growing
      mycobacterial species. Their structure was unambiguously established with a
      strategy based on both one-dimensional 31P and two-dimensional 1H-31P
      heteronuclear multiple quantum correlation spectroscopy (HMQC) and HMQC
      homonuclear Hartmann-Hahn spectroscopy NMR experiments applied to native AraLAMs
      and to AraLAMs treated in mild alkali conditions. Next to these alkali-labile
      phosphoinositides estimated at three per molecule, two other mild alkali-stable
      phosphoinositide units were identified: the expected (myo-inositol-1)-phosphate
      (3-glycerol) unit typifying the well known glycosylphosphatidylinositol anchor of
      the mannan core and, more surprisingly, one (myo-inositol-1)-phosphate-(5-beta-D
      Araf) unit having the same structure as the alkali-labile ones. Moreover, these
      four phosphoinositide units were found capping the arabinan side chains. Thus,
      their different behavior toward mild alkaline hydrolysis was explained according
      to their accessibility to the alkali reagent. This novel class of LAMs, namely
      phosphoinositols-glyceroarabinomannans (PI-GAMs), are characterized by their
      phosphoinositide units but also by the absence of fatty acid residues. These PI
      GAMs were found to elicit the secretion of tumor necrosis factor-alpha,
      suggesting that phosphoinositides are the major PI-GAM epitope involved in this
      process.

PMID- 8995237
TI  - Electrogenic L-histidine transport in neutral and basic amino acid transporter
      (NBAT)-expressing Xenopus laevis oocytes. Evidence for two functionally distinct
      transport mechanisms induced by NBAT expression.
AB  - We have investigated the neutral and basic amino acid transporter (NBAT)-induced
      transport of L-histidine in Xenopus laevis oocytes. Transport of L-histidine (pH
      7.5) was electrogenic and Na+-dependent with a 14-fold increase in L-histidine-
      (1 mM) evoked current (I(His) = -14.7 +/- 1.5 nA) in NBAT-expressing oocytes
      compared with native (water-injected or uninjected) oocytes (-1.0 +/- 0.2 nA);
      the Na+-dependent histidine transport showed a stoichiometry of 1:1
      (histidine:sodium). I(His) was stereospecific at pH 7.5 and saturable in both
      NaCl and tetramethylammonium chloride media. L-Histidine (1 mM) at pH 8.5, at
      which histidine is uncharged, evoked an Na+-independent outward current (11 +/-
      1.2 nA) in NBAT-expressing oocytes. The total inward 0.1 mM I(His) increased from
      -9 +/- 0.8 nA at pH 7.5 to -19 +/- 2.6 nA at pH 6.5, at which histidine is
      predominantly cationic. The increase in I(His) from pH 7.5 to 6.5 was found to be
      almost entirely due to the Na+-independent component. At pH 7.5, L-histidine
      weakly inhibited the Na+-independent L-arginine uptake; however, this inhibition
      was much stronger (>90%) at pH 6.5. L-Histidine transport, at pH 7.5, is
      stimulated by NBAT expression, but unlike L-phenylalanine or L-arginine
      transport, L-histidine transport is Na+-dependent and stereoselective. The
      induction of Na+-dependent L-histidine transport in NBAT-expressing oocytes
      provides new evidence that NBAT stimulates functionally distinct amino acid
      transporters including Na+-dependent L-histidine and Na+-independent L-arginine
      and L-phenylalanine transporters. The parallel induction of two different
      mechanisms argues that NBAT is not an amino acid transporter itself but, instead,
      is a transport-activating protein for a range of amino acid translocases.

PMID- 8995238
TI  - Activation of transcription of the melanoma inducing Xmrk oncogene by a GC box
      element.
AB  - Melanoma formation in Xiphophorus is caused by overexpression of the Xmrk gene.
      The promoter region of the Xmrk oncogene differs strikingly from the
      corresponding proto-oncogenic sequences and was acquired in the course of a
      nonhomologous recombination with another gene locus, D. In order to identify
      regulatory elements leading to the strong transcriptional activation of Xmrk in
      melanoma tissue and to contribute to an understanding of the role the regulatory
      locus R might play in suppressing the tumor phenotype in wild-type Xiphophorus,
      we performed functional analysis of the Xmrk oncogene promoter. Transient
      transfections in melanoma and nonmelanoma cells revealed the existence of a
      potent positive regulatory element positioned close to the transcriptional start
      site. Contained within this promoter segment is a GC-rich sequence identical to
      the binding site described for human Sp1. In vitro binding studies and
      biochemical characterizations demonstrated the existence of GC-binding proteins
      in fish that share immunological properties with members of the human Sp family
      of transcription factors and appear to be involved in the high transcriptional
      activation of the Xmrk oncogene. Since the identified cis element is functional
      in both melanoma and nonmelanoma cells, additional silencer elements suppressing
      Xmrk expression in nonpigment cells must exist, thereby suggesting a negative
      regulatory function for the genetically defined R locus.

PMID- 8995239
TI  - Phosphatidylinositol 3'-kinase and p70s6k are required for insulin but not
      bisperoxovanadium 1,10-phenanthroline (bpV(phen)) inhibition of insulin-like
      growth factor binding protein gene expression. Evidence for MEK-independent
      activation of mitogen-activated protein kinase by bpV(phen).
AB  - The hormonal regulation of insulin-like growth factor binding protein (IGFBP)-1
      and -4 mRNA was compared in serum-free primary rat hepatocyte cultures. The
      combination of dexamethasone and glucagon (Dex/Gluc) strongly increased IGFBP-1
      and IGFBP-4 mRNA levels. Insulin suppressed Dex/Gluc-stimulated IGFBP-1 but not
      IGFBP-4 mRNA levels. In contrast, the peroxovanadium compound, bisperoxovanadium
      1,10-phenanthroline (bpV(phen)), completely abrogated Dex/Gluc induction of both
      IGFBP mRNA species. Wortmannin and rapamycin blocked the inhibitory effect of
      insulin but not that of bpV(phen) on Dex/Gluc-stimulated IGFBP mRNA. Thus,
      although phosphatidylinositol 3'-kinase and p70s6k are necessary for insulin
      mediated transcriptional inhibition of the IGFBP-1 gene, a signaling pathway,
      independent of phosphatidyloinositol 3'-kinase and p70s6k, is activated by
      bpV(phen) and mediates IGFBP-1 as well as IGFBP-4 mRNA inhibition. Mitogen
      activated protein (MAP) kinase activity induced by insulin was suppressed to
      below basal levels in the presence of Dex/Gluc, whereas in response to bpV(phen),
      MAP kinase activity was high and unaffected by Dex/Gluc, consistent with a role
      of MAP kinases in bpV(phen)-mediated inhibition of IGFBP mRNA. The specific MAP
      kinase kinase (MEK) inhibitor, PD98059, inhibited insulin but not bpV(phen)
      stimulated MAP kinase activity, suggesting that MAP kinases can be activated in a
      MEK-independent fashion. Peroxovanadium compounds are strong inhibitors of
      tyrosine phosphatases, which may inhibit specific tyrosine/threonine phosphatases
      involved in the negative regulation of MAP kinases.

PMID- 8995241
TI  - Insulin-like growth factor 1 inhibits apoptosis using the phosphatidylinositol 3'
      kinase and mitogen-activated protein kinase pathways.
AB  - The role of insulin-like growth factor 1 (IGF-1) in preventing apoptosis was
      examined in differentiated PC12 cells. Induction of differentiation was achieved
      using nerve growth factor, and apoptosis was provoked by serum withdrawal. After
      4-6 h of serum deprivation, apoptosis was initiated, concomitant with a 30%
      decrease in cell number and a 75% decrease in MTT activity. IGF-1 was capable of
      preventing apoptosis at concentrations as low as 10(-9) M and as early as 4 h.
      The phosphatidylinositol 3' (PI3')-kinase inhibitors wortmannin (at
      concentrations of 10(-8) M) and LY294002 (10(-6) M) blocked the effect of IGF-1.
      The pp70 S6 kinase (pp70S6K) inhibitor rapamycin (10(-8) M) was, however, less
      effective in blocking IGF-1 action. Moreover, stable transfection of a dominant
      negative p85 (subunit of PI3'-kinase) construct in PC12 cells enhanced apoptosis
      provoked by serum deprivation. Interestingly, in the cells overexpressing the
      dominant-negative p85 protein, IGF-1 was still capable of inhibiting apoptosis,
      suggesting the existence of a second pathway involved in the IGF-1 effect.
      Blocking the mitogen-activated protein kinase pathway with the specific mitogen
      activated protein kinase/extracellular-response kinase kinase inhibitor PD098059
      (10(-5) M) inhibited the IGF-1 effect. When wortmannin and PD098059 were given
      together, the effect was synergistic. The results presented here suggest that IGF
      1 is capable of preventing apoptosis by activation of multiple signal
      transduction pathways.

PMID- 8995240
TI  - Effect of dimerization on signal transduction and biological function of
      oncogenic Ros, insulin, and insulin-like growth factor I receptors.
AB  - The avian sarcoma virus UR2 codes for an oncogenic Gag-Ros fusion protein
      tyrosine kinase (PTK). We have previously derived two retroviruses, T6 and NM1,
      coding for oncogenic Gag-insulin receptor and Gag-insulin-like growth factor I
      receptor (IGFR) fusion proteins, respectively. The Gag-IGFR fusion protein
      dimerizes, whereas Gag-Ros does not. To identify sequences affecting dimerization
      and the effect of dimerization on signaling and biological functions, we
      generated recombinants exchanging the extracellular and transmembrane sequences
      among the three fusion receptors. The presence of multiple cysteines in the Gag
      sequence appears to preclude dimerization, since deletion of the 3' cysteine
      residue allows for dimerization. Most of the chimeric receptors retain high PTK
      activity and induce transformation regardless of their configuration on the cell
      surface. UT, a UR2/T6 chimera, retained mitogenic activity but has a markedly
      reduced transforming ability, while UN7, a UR2/NM1 recombinant, which also
      harbors Y950F and F951S mutations in IGFR, exhibits dramatic reductions in both
      activities. All of the fusion receptors can phosphorylate insulin receptor
      substrate 1 and activate PI 3-kinase. UT protein induces Shc phosphorylation,
      whereas UN7 protein does not, but both are unable to activate mitogen-activated
      protein kinase. Our results show that overexpressed oncogenic Gag-fusion
      receptors do not require dimerization for their signaling and transforming
      functions and that the extracellular and transmembrane sequences of a receptor
      PTK can affect its specific substrate interactions.

PMID- 8995242
TI  - Carbohydrate-mediated regulation of interaction of Vibrio cholerae hemolysin with
      erythrocyte and phospholipid vesicle.
AB  - Vibrio cholerae hemolysin is an extracellular pore-forming monomeric protein with
      a native molecular weight of about 60,000. In this study, we showed that the
      hemolysin interacted with immobilized phospholipids and cholesterol and formed
      oligomers in vesicles constituted from phospholipids alone with a stoichiometry
      identical to those produced in rabbit erythrocyte membrane. However, the
      hemolysin bound to glycoproteins with terminal beta1-galactosyl residues and an
      association constant of 9.4 x 10(7) M(-1) was estimated for the hemolysin
      asialofetuin complex by solid phase binding assay. Oligomerization of the
      hemolysin in lipid bilayer converted the sugar-binding monomer to a lectin with
      strong carbohydrate-dependent hemagglutinating activity accompanied by
      inactivation of hemolytic activity and loss in ability to interact with
      phospholipids. There was no evidence for erythrocyte surface carbohydrates
      playing an essential role in interaction of the hemolysin with the cell. However,
      specific glycoproteins inhibited hemolysis of rabbit erythrocytes as well as
      interaction of the hemolysin with phospholipid. The results suggest (i) V.
      cholerae hemolysin is a monomer with distinct domains associated with specific
      binding to carbohydrates and interaction with lipids, (ii) the pore-forming
      property depends solely on the protein-lipid interaction with no evidence for
      involvement of sugars, and (iii) specific sugars can down-regulate the ability of
      the hemolysin to form pores in lipid bilayers.

PMID- 8995243
TI  - Ras-dependent, Ca2+-stimulated activation of nuclear factor of activated T cells
      by a constitutively active Cbl mutant in T cells.
AB  - T cell receptor (TCR) stimulation induces rapid tyrosine phosphorylation of
      cellular proteins, including Cbl, a protooncogene product whose function remains
      unclear. As a first step toward elucidating the function of Cbl in TCR-initiated
      signaling, we evaluated the ability of wild-type Cbl or a transforming Cbl mutant
      (70Z/3) to induce transcriptional activation of a nuclear factor of activated T
      cells (NFAT) element derived from the interleukin 2 (IL2) promoter in transiently
      cotransfected Jurkat-TAg T cells. 70Z/3, but not Cbl, caused NFAT activation
      which was significantly enhanced by stimulation with calcium ionophore, and was
      drastically reduced by cyclosporin A pretreatment. A point mutation of a
      potential phosphatidylinositol 3-kinase (PI3-K) binding site (Y731EAM to Y731EAC)
      in 70Z/3 disrupted the association of PI3-K with 70Z/3, but did not reduce the
      induction of NFAT activity, suggesting that the interaction between Cbl and PI3-K
      is not required in the 70Z/3-mediated induction of NFAT. Additional mapping
      studies indicated that defined deletions of C-terminal 70Z/3 sequences affected
      to a variable degree its ability to stimulate NFAT activity. Strikingly, deletion
      of 346 C-terminal residues augmented this activity, whereas removal of 20
      additional residues abolished it. Coexpression of dominant negative Ras abrogated
      the basal or ionomycin-stimulated, 70Z/3-mediated NFAT activation, suggesting a
      functional Ras is required for this activation. These results implicate Cbl in
      Ras-dependent signaling pathways which lead to NFAT activation.

PMID- 8995245
TI  - Mechanistic studies on the inactivation of the proteasome by lactacystin in
      cultured cells.
AB  - The natural product lactacystin exerts its cellular antiproliferative effects
      through a mechanism involving acylation and inhibition of the proteasome, a
      cytosolic proteinase complex that is an essential component of the ubiquitin
      proteasome pathway for intracellular protein degradation. In vitro, lactacystin
      does not react with the proteasome; rather, it undergoes a spontaneous conversion
      (lactonization) to the active proteasome inhibitor, clasto-lactacystin beta
      lactone. We show here that when the beta-lactone is added to mammalian cells in
      culture, it rapidly enters the cells, where it can react with the sulfhydryl of
      glutathione to form a thioester adduct that is both structurally and functionally
      analogous to lactacystin. We call this adduct lactathione, and like lactacystin,
      it does not react with the proteasome, but can undergo lactonization to yield
      back the active beta-lactone. We have studied the kinetics of this reaction under
      appropriate in vitro conditions as well as the kinetics of lactathione
      accumulation and proteasome inhibition in cells treated with lactacystin or beta
      lactone. The results indicate that only the beta-lactone (not lactacystin) can
      enter cells and suggest that the formation of lactathione serves to concentrate
      the inhibitor inside cells, providing a reservoir for prolonged release of the
      active beta-lactone.

PMID- 8995244
TI  - A novel transcription factor regulates expression of the vacuolar H+-ATPase B2
      subunit through AP-2 sites during monocytic differentiation.
AB  - During monocyte-to-macrophage differentiation, the cellular content of vacuolar
      H+-ATPase (V-ATPase) increases more than 4-fold. We have shown previously that
      amplified expression of the B2 subunit of the V-ATPase occurs solely by increased
      transcription, and that the 5'-untranslated region of the B2 gene, containing
      multiple consensus binding sites for the transcription factors AP-2 and Sp1, is
      required for this expression. The present study demonstrates that AP-2 binding
      sequences are essential for increased transcription from the B2 promoter during
      monocyte-macrophage differentiation and that AP-2, expressed exogenously in THP-1
      and other cells, activates transcription from the B2 promoter. In mobility shift
      assays, a nuclear factor from THP-1 and U-937 cells was identified that binds to
      several AP-2 response elements within the B2 promoter, but does not react with AP
      2 antibodies, and has a DNA sequence binding affinity profile that differs from
      AP-2. These findings suggest that a novel AP-2-like transcription factor is
      responsible for V-ATPase B subunit amplification during monocyte differentiation.

PMID- 8995246
TI  - Influence of acidic residues and the kink in the active-site helix on the
      properties of the disulfide oxidoreductase DsbA.
AB  - The catalytic disulfide bond Cys30-Cys33 of the disulfide oxidoreductase DsbA
      from Escherichia coli is located at the amino terminus of an alpha-helix, which
      has a kink caused by insertion of a tripeptide (residues 38-40). The oxidative
      force of DsbA (E'O = -125 mV) mainly results from the low pKa of 3.4 of its Cys30
      thiol. To investigate the role of the kink and the electrostatic contribution of
      Glu37 and Glu38 to the redox properties of DsbA, we have characterized a series
      of DsbA variants (delta38-40, delta38-40/H41P, E37Q, E38Q, and E37Q/E38Q). In
      contrast to theoretical predictions, the redox potentials of the variants are
      almost unchanged, and the pKa values of Cys30 do not differ by more than 0.5
      units from that of DsbA wild type. All variants show the same in vivo activity
      and dependence of redox potential on ionic strength as the wild type. The
      mutations have no influence on the polypeptide specificity of the protein, which
      is independent of the isoelectric point of the polypeptide substrate and most
      pronounced at acidic pH. We conclude that neither the kink in the active-site
      helix nor Glu37 and Glu38 are critical for the physical properties of DsbA.

PMID- 8995247
TI  - CspA, the major cold-shock protein of Escherichia coli, is an RNA chaperone.
AB  - CspA, the major cold-shock protein of Escherichia coli, is dramatically induced
      during the cold-shock response. The amino acid sequence of CspA shows 43%
      identity to the "cold-shock domain" of the eukaryotic Y-box protein family, which
      interacts with RNA and DNA to regulate their functions. Here, we demonstrate that
      CspA binds to RNA as a chaperone. First, CspA cooperatively binds to heat
      denatured single-stranded RNA if it is larger than 74 bases, causing a supershift
      in gel electrophoresis. A minimal concentration of CspA at 2.7 x 10(-5) M is
      absolutely required for this cooperative binding, which is sufficiently lower
      than the estimated cellular concentration of CspA (10(-4) M) in cold-shocked
      cells. No specific RNA sequences for CspA binding were identified, indicating
      that it has a broad sequence specificity for its binding. When the 142-base 5'
      untranslated region of the cspA mRNA was used as a substrate for ribonucleases A
      and T1, the addition of CspA significantly stimulated RNA hydrolysis by
      preventing the formation of RNase-resistant bands due to stable secondary
      structures in the 5'-untranslated region. These results indicate that binding of
      CspA to RNA destabilizes RNA secondary structures to make them susceptible to
      ribonucleases. We propose that CspA functions as an RNA chaperone to prevent the
      formation of secondary structures in RNA molecules at low temperature. Such a
      function may be crucial for efficient translation of mRNAs at low temperatures
      and may also have an effect on transcription.

PMID- 8995248
TI  - Q-band electron nuclear double resonance (ENDOR) and X-band EPR of the
      sulfobetaine 12 heat-treated cytochrome c oxidase complex.
AB  - Heat treatment of the bovine cytochrome c oxidase complex in the zwitterionic
      detergent sulfobetaine 12 (SB-12) results in loss of subunit III and the
      appearance of a type II copper center as characterized by electron paramagnetic
      resonance (EPR) spectroscopy. Previous authors (Nilsson, T., Copeland, R. A.,
      Smith, P. A., and Chan, S. I. (1988) Biochemistry 27, 8254-8260) have interpreted
      this type II copper center as a modified version of the CuA site. By using
      electron nuclear double resonance spectroscopy, it is found that the CuA proton
      and nitrogen resonances remain present in the SB-12 heat-treated enzyme and that
      three new nitrogen resonances appear having hyperfine coupling constants
      consistent with histidine ligation. These hyperfine coupling constants correlate
      well with those recently found for the CuB histidines from the cytochrome aa(3)
      600 quinol oxidase from Bacillus subtilis (Fann, Y. C., Ahmed, I., Blackburn, N.
      J., Boswell, J. S., Verkhovskaya, M. L., Hoffman, B. M., and Wikstr9om, M. (1995)
      Biochemistry 34, 10245-10255). In addition, the total EPR-detectable copper
      concentration per enzyme molecule approximately doubles upon SB-12 heat
      treatment. Finally, the observed type II copper EPR spectrum is virtually
      indistinguishable from the EPR spectrum of CuB of the as-isolated cytochrome bo3
      complex from Escherichia coli. These data indicate that the type II copper
      species that appears results from a breaking of the strong antiferromagnetic
      coupling of the heme a3-CuB binuclear center.

PMID- 8995249
TI  - Site-directed mutations at residue 251 of the photosystem II D1 protein of
      Chlamydomonas that result in a nonphotosynthetic phenotype and impair D1
      synthesis and accumulation.
AB  - In Cyanobacteria and Chlamydomonas reinhardtii, substitution of valine for
      alanine at position 251 of the photosystem II D1 protein in the loop between
      transmembrane helices IV and V confers resistance to herbicides that reduce
      photosystem II function and increases sensitivity to photoinhibition. Using site
      directed mutagenesis and chloroplast transformation in Chlamydomonas we have
      examined further the role of residue 251 in relation to D1 structure, function,
      and photosynthetic performance. Of the 12 different amino acid substitutions for
      Ala251 introduced at this position, five (Arg, Asp, Gln, Glu, and His) resulted
      in a nonphotosynthetic phenotype. Transformants with the Arg251 substitution
      synthesize a normal sized 32-kDa D1 protein with greatly reduced stability. The
      Gln, Glu, His, and Asp transformants make a 33-34-kDa form of the D1 protein of
      varying stability as well as an immunologically related polypeptide of 24-25 kDa
      corresponding to the N-terminal portion of D1 that is unstable and appears to be
      an aborted D1 translation product. All mutant forms of the D1 protein are
      intrinsic to the thylakoids. In contrast to previous studies in Cyanobacteria
      showing that residues in the IV-V loop can be mutated or deleted without loss of
      photosynthetic competence, our results suggest that Ala251 has a key role in the
      structure and function of the IV-V loop region.

PMID- 8995250
TI  - Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in
      EGF receptor-mediated tyrosine phosphorylation.
AB  - Recent evidence indicates that reactive oxygen species (ROS) may function as
      intracellular messengers in receptor signaling pathways. The possible role of ROS
      in epidermal growth factor (EGF) signaling was therefore investigated.
      Stimulation of A431 human epidermoid carcinoma cells with EGF resulted in a
      transient increase in the intracellular concentration of ROS, measured with the
      oxidation-sensitive fluorescent probe 2',7'-dichlorofluorescin diacetate and
      laser-scanning confocal microscopy. The predominant ROS produced appeared to be
      H2O2, because the EGF-induced increase in fluorescence was completely abolished
      by incorporation of catalase into the cells by electroporation. The elimination
      of H2O2 by catalase also inhibited the EGF-induced tyrosine phosphorylation of
      various cellular proteins including the EGF receptor and phospholipase C-gamma1.
      The dependence of H2O2 production on the intrinsic tyrosine kinase activity of
      the EGF receptor and the autophosphorylation sites located in its COOH-terminal
      tail was investigated. EGF failed to induce H2O2 generation in cells expressing a
      kinase-inactive EGF receptor. However, normal H2O2 generation was observed in
      cells expressing a mutant receptor from which the 126 COOH-terminal amino acids
      had been deleted to remove four (out of the total of five) autophosphorylation
      sites. These results suggest that EGF-induced H2O2 formation requires the kinase
      activity but probably not the autophosphorylation sites of the EGF receptor and
      that inhibition of protein tyrosine phosphatase activity by H2O2 may be required
      for EGF-induced protein tyrosine phosphorylation to be manifested.

PMID- 8995251
TI  - Purification of a novel phospholipase A2 from bovine seminal plasma.
AB  - Phospholipases A2 are enzymes believed to play important roles in numerous
      physiological systems including sperm cell maturation. Relatively little work
      has, however, been devoted to study these enzymes in seminal plasma. We therefore
      undertook the purification and characterization of this enzyme from bovine
      seminal plasma. After a 330-fold purification, an activity corresponding to a
      protein of 100 kDa was identified by gel filtration. SDS-polyacrylamide gel
      electrophoresis analysis of the purified fraction revealed the presence of a 60
      kDa band that comigrated with the activity during ion-exchange and gel filtration
      chromatography as well as polyacrylamide gel electrophoresis. The enzyme
      possessed a pH optimum around pH 6.5 and was calcium-dependent. Using isoelectric
      focusing, its isoelectric point was determined to be 5.6 +/- 0.07. The enzymatic
      activity was resistant to p-bromophenacyl bromide, but was sensitive to gossypol
      and dithiothreitol. The enzyme was 2 orders of magnitude more active toward
      micelles formed with deoxycholate than with Triton X-100. Slight differences in
      the specificity toward head groups and/or sn-2-side chains were found in both
      assay systems. The enzyme was acid-labile and did not display affinity for
      heparin. It would therefore appear that the phospholipase A2 form isolated from
      bovine seminal plasma is of a novel type.

PMID- 8995253
TI  - Tripartite hemolysin BL from Bacillus cereus. Hemolytic analysis of component
      interactions and a model for its characteristic paradoxical zone phenomenon.
AB  - Hemolysin BL (HBL) is a unique membrane-lytic toxin from Bacillus cereus composed
      of three distinct proteins, designated B, L1, and L2. HBL produces a paradoxical
      zone phenomenon in gel diffusion assays in sheep blood agar. Lysis does not begin
      immediately adjacent to the source of diffusion; rather, it begins several
      millimeters away. Cells near the source and at intersections of lysis zones
      remain intact longer. Here, we developed a spectrophotometric hemolysis assay
      system that measures the activities of the individual HBL components and used it
      to analyze the mechanisms of hemolysis and the paradoxical zone phenomenon. The B
      component was rate-limiting, and erythrocytes were slowly primed by B at an
      optimal concentration of about 1.3 nM to rapid lytic action by the combination of
      the L components (L(1+2)). All of the individual components bound to cells
      independently, and membrane-associated HBL components were neutralized by
      specific antibodies, suggesting that lysis was caused by formation of a membrane
      attack complex on the cell surface. Osmotic protection experiments indicate a
      colloid osmotic lysis mechanism. Concentrations of the B component above 1.3 nM
      caused inhibition of L1-mediated lysis, and L1 inhibited the priming reaction of
      B over a similar concentration range. From analyses of spectrophotometric and
      diffusion assays we constructed a basic model for the interactions between HBL
      components and for the paradoxical zone phenomenon in blood agar. In the latter,
      areas of slow lysis near diffusion sources are caused primarily by the
      accumulation of inhibitory levels of L1 reached before cells are primed by B.

PMID- 8995252
TI  - The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1
      integrin stimulation in B cells and binds to p130cas.
AB  - Integrin ligation initiates intracellular signaling events, among which are the
      activation of protein tyrosine kinases. The related adhesion focal tyrosine
      kinase (RAFTK), also known as PYK2 and CAKbeta, is a tyrosine kinase that is
      homologous to the focal adhesion kinase (FAK) p125FAK. The structure of RAFTK is
      similar to p125FAK in that it lacks a transmembrane region, does not contain Src
      homology 2 or 3 domains, and has a proline-rich region in its C terminus. Here we
      report that RAFTK is a target for beta1-integrin-mediated tyrosine
      phosphorylation in both transformed and normal human B cells. Ligation of the B
      cell antigen receptor also induced tyrosine phosphorylation of RAFTK.
      Phosphorylation of RAFTK following integrin- or B cell antigen receptor-mediated
      stimulation was decreased by prior treatment of cells with cytochalasin B,
      indicating that this process was at least partially cytoskeleton-dependent. One
      of the tyrosine-phosphorylated substrates after integrin stimulation in
      fibroblasts is p130cas, which can associate with p125FAK. RAFTK also interacted
      constitutively with p130cas in B cells, since p130cas was detected in RAFTK
      immunoprecipitates. Although the function of RAFTK remains unknown, these data
      suggest that RAFTK may have a significant function in integrin-mediated signaling
      pathways in B cells.

PMID- 8995254
TI  - The G beta gamma complex of the yeast pheromone response pathway. Subcellular
      fractionation and protein-protein interactions.
AB  - Genetic evidence suggests that the yeast STE4 and STE18 genes encode G beta and G
      gamma subunits, respectively, that the G betagamma complex plays a positive role
      in the pheromone response pathway, and that its activity is subject to negative
      regulation by the G alpha subunit (product of the GPA1 gene) and to positive
      regulation by cell-surface pheromone receptors. However, as yet there is no
      direct biochemical evidence for a G betagamma protein complex associated with the
      plasma membrane. We found that the products of the STE4 and STE18 genes are
      stably associated with plasma membrane as well as with internal membranes and
      that 30% of the protein pool is not tightly associated with either membrane
      fraction. A slower-migrating, presumably phosphorylated, form of Ste4p is
      enriched in the non-membrane fraction. The Ste4p and Ste18p proteins that had
      been extracted from plasma membranes with detergent were found to co-sediment as
      an 8 S particle under low salt conditions and as a 6 S particle in the presence
      of 0.25 M NaCl; the Ste18p in these fractions was precipitated with anti-Ste4p
      antiserum. Under the conditions of our assay, Gpa1p was not associated with
      either particle. The levels of Ste4p and Ste18p accumulation in mutant cells
      provided additional evidence for a G betagamma complex. Ste18p failed to
      accumulate in ste4 mutant cells, and Ste4p showed reduced levels of accumulation
      and an increased rate of turnover in ste18 mutant cells. The gpa1 mutant blocked
      stable association of Ste4p with the plasma membrane, and the ste18 mutant
      blocked stable association of Ste4p with both plasma membranes and internal
      membranes. The membrane distribution of Ste4p was unaffected by the ste2 mutation
      or by down-regulation of the cell-surface receptors. These results indicate that
      at least 40% of Ste4p and Ste18p are part of a G betagamma complex at the plasma
      membrane and that stable association of this complex with the plasma membrane
      requires the presence of G alpha.

PMID- 8995255
TI  - Glial cell line-derived neurotrophic factor induces Ret-mediated lamellipodia
      formation.
AB  - Ret is a receptor tyrosine kinase required during embryogenesis for the survival
      of enteric and sympathetic neuroblasts. Recently, glial cell line-derived
      neurotrophic factor (GDNF) has been identified as a ligand for Ret. We
      investigated early events in GDNF-induced signal transduction. We show that GDNF
      activates the Ras-ERK2 signaling pathway in SK-N-MC cells stably transfected with
      a full-length Ret construct. In addition, activation of Ret tyrosine kinase
      activity, either via GDNF stimulation of full-length Ret or via epidermal growth
      factor stimulation of an epidermal growth factor receptor-Ret chimeric receptor,
      results in phosphatidylinositol 3-kinase activation and phosphatidylinositol 3
      kinase-dependent formation of large lamellipodia. Our results indicate that GDNF
      can serve as a genuine ligand for Ret. In addition, we show that GDNF can induce
      Ret-mediated formation of lamellipodia, cell surface protrusions that are
      implicated in neuritogenesis.

PMID- 8995256
TI  - Arginine-specific regulation mediated by the Neurospora crassa arg-2 upstream
      open reading frame in a homologous, cell-free in vitro translation system.
AB  - Translational control mediated by an upstream open reading frame (uORF) in the 5'
      leader of the Neurospora crassa arg-2 mRNA was reconstituted in a homologous,
      cell-free in vitro translation system. A cell-free N. crassa system was developed
      that required the presence of cap and poly(A) on RNA for maximal translation and
      that was amino acid-dependent. The 24-codon arg-2 uORF, when placed in the 5'
      leader region of capped and adenylated synthetic luciferase RNAs, conferred Arg
      specific negative regulation in this system. Improving the uORF translation
      initiation context decreased luciferase production and only slightly increased
      the magnitude of Arg-specific regulation. Mutation of uORF Asp codon 12 to Asn,
      which eliminates Arg-specific regulation in vivo, eliminated regulation in vitro.
      Elimination of the uORF translation initiation codon also eliminated Arg-specific
      regulation. Arg-specific regulation in vitro appeared to be reversible. Control
      of RNA stability did not appear to be a primary component of Arg-specific
      regulation in vitro. Comparison of the effects of adding Arg to in vitro
      translation reactions with adding compounds related to Arg indicated that Arg
      specific translational regulation was specific for L-arginine.

PMID- 8995257
TI  - Fourier transform infrared spectroscopy study of the secondary structure of the
      gastric H+,K+-ATPase and of its membrane-associated proteolytic peptides.
AB  - Membrane topology of the H+,K+-ATPase has been studied after proteolytic
      degradation of the protein by proteinase K. Proteinase K had access to either the
      cytoplasmic part of the protein or to both sides of the membrane. Fourier
      transform infrared attenuated total reflection spectroscopy indicated that
      membrane-associated domain of the protein represented about 55% of the native
      protein, meanwhile the cytoplasmic part represented only 27% of the protein. The
      secondary structure of the ATPase and of its membrane-associated domains was
      investigated by infrared spectroscopy. The secondary structure of the membrane
      associated structures and of the entire protein was quite similar (alpha-helices,
      35%; beta-sheets, 35%; turns, 20%; random, 15%). These data were in agreement
      with 10 alpha-helical transmembrane segments but suggested a participation of
      beta-sheet structures in the membrane-associated part of the protein. Polarized
      infrared spectroscopy indicated that the alpha-helices were oriented nearly
      perpendicular to the membrane plane. No preferential orientation could be
      attributed to the beta-sheets. Monitoring the amide hydrogen/deuterium exchange
      kinetics demonstrated that the membrane associated part of the ATPase molecule is
      characterized by a relatively high accessibility to the solvent, quite different
      from that observed for bacteriorhodopsin membrane segments.

PMID- 8995258
TI  - The p42/p44 mitogen-activated protein kinase cascade is determinant in mediating
      activation of the Na+/H+ exchanger (NHE1 isoform) in response to growth factors.
AB  - The ubiquitously expressed Na+/H+ exchanger NHE1 is the target of multiple
      signaling pathways, including those activated by tyrosine kinase receptors, G
      protein-coupled receptors, and integrins. The intracellular pathways leading to
      activation of NHE1 are poorly understood. To gain more insight into these
      activation pathways, we examined the role of mitogen-activated protein kinases
      (MAPKs) as potential mediators of NHE1 activation by extracellular stimuli such
      as growth factors and hyperosmotic stress. Whereas p44 MAPK does not appear to
      phosphorylate NHE1 in vitro, we found that inhibition of the p42/p44 MAPK
      signaling by expression of a dominant negative form of p44 MAPK, by expression of
      the MAP kinase phosphatase MKP-1, or by inhibition of MAPK kinase 1 (MKK1) with
      the PD 98059 compound reduced by 50-60% NHE1 activation in response to growth
      factors. This inhibitory effect also was observed in C-terminal NHE1 deletion
      mutants in which the major phosphorylation sites have been deleted. Furthermore,
      the use of a CCL39-derived cell line expressing an estradiol-regulated form of
      oncogenic Raf-1 (CCL39-deltaRaf-1:ER) revealed that the exclusive activation of
      the Raf --> MKK1 --> p42/p44 MAPK cascade was capable of inducing NHE1 activation
      to the same extent as potent growth factors like thrombin. Together, our findings
      demonstrate that the p42/p44 MAPK cascade plays a predominant role in the
      regulation of NHE1 by growth factors, an action that is mediated via accessory
      proteins that remain to be identified. In contrast, we found no evidence in favor
      of the contribution of any MAPK, p42/p44, p38 MAPKs, and Jun kinase, in NHE1
      activation by osmotic stress.

PMID- 8995259
TI  - Amino acid residue 149 of lecithin:cholesterol acyltransferase determines
      phospholipase A2 and transacylase fatty acyl specificity.
AB  - Human LCAT prefers phosphatidylcholine (PC) with sn-1-palmitoyl-2-oleoyl PC
      (POPC) as substrate for cholesteryl ester synthesis, whereas rat LCAT (which is
      92% similar in amino acid sequence) prefers sn-1-palmitoyl-2-arachidonoyl PC
      (PAPC). Six recombinant human LCAT cDNA clones were constructed with unique
      clusters of rat sequence substitutions in the human background spanning the
      region encoding amino acids 121-296. Media from transfected COS cells expressing
      each of the constructs were assayed for LCAT cholesterol esterification (CE) or
      phospholipase A2 (PLA2) activity using substrate particles containing POPC or
      PAPC. The PAPC/POPC CE activity ratio of the cluster 1 construct (amino acids 149
      158) was 1.3, resembling rat LCAT, whereas cluster 2-5 clones produced CE
      activity ratios <0.3, unchanged from human LCAT. The cluster 6 clone
      (Y292H/W294F) had an intermediate ratio (0.6). Similar results were observed for
      LCAT PLA2 activity. In additional studies, position 149 of human LCAT was changed
      to the rat sequence (hE149A) and compared to a triple mutation containing the
      remainder of the cluster 1 changes (G151R/E154D/R158Q). CE and PLA2 activity
      ratio for the hE149A construct was >1.7, similar to rat LCAT, whereas the triple
      mutation construct retained a ratio similar to human LCAT (<0.6). Thus, a single
      amino acid substitution (E149A) was sufficient to alter the fatty acyl
      specificity of human LCAT to that of rat LCAT, with an increase in activity
      toward PAPC. This is the first example of a point mutation in an enzyme with PLA2
      activity that results in an increase in activity toward arachidonic acid.

PMID- 8995260
TI  - Muscarinic agonists induce phosphorylation-independent activation of the NHE-1
      isoform of the Na+/H+ antiporter in salivary acinar cells.
AB  - Cholinergic agonists stimulate isotonic fluid secretion in the parotid gland.
      This process is driven by the apical exit of Cl-, which enters the cells partly
      via Cl-/HCO-3 exchange across the basolateral membrane. Acidification of the
      cytosol by the extrusion of HCO-3 is prevented by the concomitant activation of
      the Na+/H+ exchanger (NHE), which is directly activated by cholinergic
      stimulation. Multiple isoforms of the NHE have been described in mammalian cells,
      but the particular isoform(s) present in salivary glands and their mechanism of
      activation have not been defined. Reverse transcriptase-polymerase chain reaction
      with isoform-specific primers was used to establish that NHE-1 and NHE-2, but not
      NHE-3 or NHE-4, are expressed in parotid glands. The presence of NHE-1 was
      confirmed by immunoblotting and immunofluorescence, which additionally
      demonstrated that this isoform is abundant in the basolateral membrane of acinar
      cells. The predominant role of NHE-1 in carbachol-induced Na+/H+ exchange was
      established pharmacologically using HOE694, an inhibitor with differential
      potency toward the individual isoforms. Because muscarinic agonists induce
      stimulation of protein kinases in acinar cells, we assessed the role of
      phosphorylation in the activation of the antiport. Immunoprecipitation
      experiments revealed that, although NHE-1 was phosphorylated in the resting
      state, no further phosphorylation occurred upon treatment with carbachol. Similar
      phosphopeptide patterns were observed in control and carbachol-treated samples.
      Together, these findings indicate that NHE-1, the predominant isoform of the
      antiporter in the basolateral membrane of acinar cells, is activated during
      muscarinic stimulation by a phosphorylation-independent event. Other processes,
      such as association of Ca2+-calmodulin complexes to the cytosolic domain of the
      antiporter, may be responsible for the activation of Na+/H+ exchange.

PMID- 8995261
TI  - Structural features of phi29 single-stranded DNA-binding protein. I. Environment
      of tyrosines in terms of complex formation with DNA.
AB  - The single-stranded DNA-binding protein (SSB) of Bacillus subtilis phage phi29 is
      absolutely required for viral DNA replication in vivo. About approximately 95% of
      the intrinsic tyrosine fluorescence of phi29 SSB is quenched upon binding to
      ssDNA, making tyrosine residues strong candidates to be directly involved in
      complex formation with ssDNA. Thus, we have studied the spectroscopic properties
      of the phi29 SSB tyrosines (Tyr-50, Tyr-57, and Tyr-76) using steady-state and
      time-resolved fluorescence measurements. phi29 SSB tyrosines do not seem to be
      highly restricted by strong interactions with neighbor residues, as suggested by
      (i) the high value of the average quantum yield of the phi29 SSB fluorescence
      emission (phiF = 0.067 +/- 0.010), (ii) the fast motions of the tyrosine side
      chains (phi(short) = 0.14 +/- 0.06 ns), and (iii) the lack of tyrosinate emission
      at neutral pH. Stern-Volmer analysis of the quenching by acrylamide and I-
      indicates that phi29 SSB tyrosines are surrounded by a negatively charged
      environment and located in a relatively exposed protein domain, accessible to the
      solvent and, likely, to ssDNA. Changes in the intrinsic fluorescence upon ssDNA
      binding allowed us to determine that temperature has an opposite effect on the
      thermodynamic parameters K (intrinsic binding constant) and omega (cooperativity)
      defining phi29 SSB-poly(dT) interaction, the effective DNA binding constant,
      K(eff) = K omega, being largely independent of temperature. Altogether, the
      fluorescent properties of phi29 SSB tyrosines are consistent with a direct
      participation in complex formation with ssDNA.

PMID- 8995262
TI  - Structural features of phi29 single-stranded DNA-binding protein. II. Global
      conformation of phi29 single-stranded DNA-binding protein and the effects of
      complex formation on the protein and the single-stranded DNA.
AB  - The strand-displacement mechanism of Bacillus subtilis phage phi29 DNA
      replication occurs through replicative intermediates with high amounts of single
      stranded DNA (ssDNA). These ssDNA must be covered by the viral ssDNA-binding
      protein, phi29 SSB, to be replicated in vivo. To understand the characteristics
      of phi29 SSB-ssDNA complex that could explain the requirement of phi29 SSB, we
      have (i) determined the hydrodynamic behavior of phi29 SSB in solution and (ii)
      monitored the effect of complex formation on phi29 SSB and ssDNA secondary
      structure. Based on its translational frictional coefficient (3.5 +/- 0.1) x
      10(8) gs(-1), and its rotational correlation time, 7.0 +/- 0.5 ns, phi29 SSB was
      modeled as a nearly spherical ellipsoid of revolution. The axial ratio (p = a/b)
      could range from 0.8 to 1.0 (oblate model, a < b) or 1.0 to 3.2 (prolate model, a
      > b). Far-UV CD spectra, indicated that phi29 SSB is highly organized within a
      wide range of temperatures (15 to 50 degrees C), being mainly constituted by beta
      sheet elements (approximately 50%, at pH 7). Complex formation with ssDNA,
      although inducing minimal changes on the global conformation of phi29 SSB, had a
      clear stabilizing effect against pH and temperature increase of the solution
      samples. On the other hand, phi29 SSB binding leads to non-conservative changes
      of the near-UV CD spectra of ssDNA, which are consistent with different nearest
      neighbor interactions of the nucleotide bases upon complex formation. The above
      results will be compared to those reported for other SSBs and discussed in terms
      of the functional roles of phi29 SSB.

PMID- 8995263
TI  - The sixth transmembrane domains of the human B1 and B2 bradykinin receptors are
      structurally compatible and involved in discriminating between subtype-selective
      agonists.
AB  - In order to investigate the molecular basis for the ability of the human B1 and
      B2 bradykinin (BK) receptor subtypes to discriminate between subtype-selective
      ligands, we constructed chimeric proteins in which the sixth transmembrane
      domains (TM-VI) of these receptors were exchanged. The pharmacological profiles
      of the constructs were analyzed by radioligand binding in particulate
      preparations of transiently transfected HEK293 cells using the agonist [3H]des
      Arg10-kallidin and the antagonist [3H]NPC17731. The ability of these constructs
      to transmit an intracellular signal was measured in transiently transfected A10
      cells, a vascular smooth muscle cell line, by single cell Ca2+ imaging.
      Substitution of B1 TM-VI into the B2 receptor (B2(B1VI)) dramatically reduced the
      affinity of the B2-selective agonist BK, whereas the affinity of the B2-selective
      antagonist NPC17731 was unaltered. High affinity BK binding was fully regained
      when two residues, Tyr259 and Ala263, near the extracellular surface of TM-VI in
      B2(B1VI), were replaced with the corresponding residues in the wild-type B2
      receptor, which are Phe259 and Thr263. The construct B1(B2VI), produced by
      substitution of B2 TM-VI into the B1 receptor, did not support high affinity
      binding of the B1-selective agonist des-Arg10-kallidin. In contrast to BK and des
      Arg10-kallidin, the binding of the less subtype-selective agonist kallidin showed
      little sensitivity to TM-VI exchange. These results show that TM-VI in the human
      B1 and B2 BK receptor subtypes, although only 36% identical, are structurally
      compatible. Furthermore, this domain contributes significantly to the ability of
      these receptors to discriminate between the subtype-selective agonists BK and des
      Arg10-kallidin.

PMID- 8995264
TI  - Selective expression and processing of biglycan during migration of bovine aortic
      endothelial cells. The role of endogenous basic fibroblast growth factor.
AB  - Repair of the vascular lumenal surface after injury requires a controlled
      endothelial cell response that includes cell migration, proliferation, and
      remodeling of the extracellular matrix. These cellular processes are modulated by
      growth factors that are released or activated following cell injury. When
      endothelial cell migration is stimulated in response to monolayer wounding in
      vitro, cells increase synthesis of small leucine-rich dermatan sulfate
      proteoglycans (PGs) (Kinsella, M. G., and Wight, T. N. (1986) J. Cell Biol. 102,
      679-687). However, the identity of the PGs that are increased during cell
      migration and the factors that affect this modulation have not been identified.
      We now report that basic fibroblast growth factor (bFGF) is responsible for the
      transient increase of [35S]sulfate incorporation into PGs following monolayer
      wounding. SDS-polyacrylamide gel electrophoresis analysis revealed that bFGF
      treated and wounded cultures increase both biglycan core protein synthesis and
      biglycan proteolytic processing, which results in the accumulation of a
      approximately 20-kDa N-terminal biglycan fragment in the culture media. Biglycan
      RNA steady-state levels also selectively increase 2- to 3-fold after wounding or
      bFGF treatment. Finally, immunocytochemical staining localizes biglycan to the
      tips and edges of lamellopodia on migrating cells, indicating that biglycan is
      found at loci at which the formation and dissolution of adhesion plaques occurs,
      consistent with hypotheses that predict involvement of biglycan in the control of
      cell migration. Taken together, these results suggest that release of endogenous
      bFGF is primarily responsible for altered biglycan expression, synthesis, and
      proteolytic processing as endothelial cells migrate after wounding.

PMID- 8995265
TI  - Alternate energy coupling of ArsB, the membrane subunit of the Ars anion
      translocating ATPase.
AB  - The arsenical resistance (ars) operon of the conjugative R-factor R773 confers
      resistance to arsenical and antimonial compounds in Escherichia coli, where
      resistance results from active extrusion of arsenite catalyzed by the products of
      the arsA and arsB genes. Previous in vivo studies on the energetics of arsenite
      extrusion showed that expression of both genes produced an ATP-coupled arsenite
      extrusion system that was independent of the electrochemical proton gradient. In
      contrast, in cells expressing only the arsB gene, arsenite extrusion was coupled
      to electrochemical energy and independent of ATP, suggesting that the Ars
      transport system exhibits a dual mode of energy coupling depending on the subunit
      composition. In vitro the ArsA-ArsB complex has been shown to catalyze ATP
      coupled uptake of 73AsO2(-1) in everted membrane vesicles. However, transport
      catalyzed by ArsB alone has not previously been observed in vitro. In this study
      we demonstrate everted membrane vesicles prepared from cells expressing only arsB
      exhibit uptake of 73AsO2(-1) coupled to electrochemical energy.

PMID- 8995266
TI  - Cloning, purification, and characterization of the Shigella boydii dGTP
      triphosphohydrolase.
AB  - The nucleotide sequence of the Shigella boydii dgt gene, which encodes the enzyme
      deoxyguanosine triphosphate triphosphohydrolase (dGTPase, EC 3.1.5.1), has been
      determined. The 1515-nucleotide Shigella dgt open reading frame has been
      subcloned into a T7 RNA polymerase-based expression vector. The resulting
      expressed protein has been purified to homogeneity using a novel single-day
      chromatographic regime. The protocol includes ion exchange, affinity, and
      hydrophobic interaction chromatography. The purified 505-amino acid (59.4 kDa)
      protein exists in solution as a heat-stable homotetramer, and enzymatic assays
      reveal that the expressed enzyme is fully active. Substrate specificity can be
      explained by the array of potential hydrogen bond donors/acceptors displayed on
      the base moiety of the (deoxy)nucleoside triphosphate. Shigella dGTPase can be
      inhibited by the addition of stoichiometric amounts of reducing agents. The loss
      of activity is both time- and concentration-dependent and is accompanied by a
      decrease in the thermal stability of the enzyme. Shigella dGTPase in the fully
      reduced form is destabilized by 1.8 kcal/mol compared with the oxidized form.
      Hence, disulfide bonds play a pivotal role in the maintenance of dGTPase
      stability and enzymatic functionality. Initial Shigella dGTPase protein crystals
      have been formed.

PMID- 8995268
TI  - Ascorbate differentially regulates elastin and collagen biosynthesis in vascular
      smooth muscle cells and skin fibroblasts by pretranslational mechanisms.
AB  - Ascorbate contributes to several metabolic processes including efficient
      hydroxylation of hydroxyproline in elastin, collagen, and proteins with
      collagenous domains, yet hydroxyproline in elastin has no known function. Prolyl
      hydroxylation is essential for efficient collagen production; in contrast,
      ascorbate has been shown to decrease elastin accumulation in vitro and to alter
      morphology of elastic tissues in vivo. Ascorbate doses that maximally stimulated
      collagen production (10-200 microM) antagonized elastin biosynthesis in vascular
      smooth muscle cells and skin fibroblasts, depending on a combination of dose and
      exposure time. Diminished elastin production paralleled reduced elastin mRNA
      levels, while collagen I and III mRNAs levels increased. We compared the
      stability of mRNAs for elastin and collagen I with a constitutive gene after
      ascorbate supplementation or withdrawal. Ascorbate decreased elastin mRNA
      stability, while collagen I mRNA was stabilized to a much greater extent.
      Ascorbate withdrawal decreased collagen I mRNA stability markedly (4.9-fold),
      while elastin mRNA became more stable. Transcription of elastin was reduced 72%
      by ascorbate exposure. Differential effects of ascorbic acid on collagen I and
      elastin mRNA abundance result from the combined, marked stabilization of collagen
      mRNA, the lesser stability of elastin mRNA, and the significant repression of
      elastin gene transcription.

PMID- 8995267
TI  - Identification of A2a adenosine receptor domains involved in selective coupling
      to Gs. Analysis of chimeric A1/A2a adenosine receptors.
AB  - Responses to adenosine are governed by selective activation of distinct G
      proteins by adenosine receptor (AR) subtypes. The A2aAR couples via Gs to
      adenylyl cyclase stimulation while the A1AR couples to Gi to inhibit adenylyl
      cyclase. To determine regions of the A2aAR that selectively couple to Gs,
      chimeric A1/A2aARs were expressed in Chinese hamster ovary cells and ligand
      binding and adenylyl cyclase activity analyzed. Replacement of the third
      intracellular loop of the A2aAR with that of the A1AR reduced maximal adenylyl
      cyclase stimulation and decreased agonist potency. Restricted chimeras indicated
      that the NH2-terminal portion of intracellular loop 3 was predominantly
      responsible for this impairment. Reciprocal chimeras composed primarily of A1AR
      sequence with limited A2aAR sequence substitution stimulated adenylyl cyclase and
      thus supported these findings. A lysine and glutamic acid residue were identified
      as necessary for efficient A2aAR-Gs coupling. Analysis of chimeric receptors in
      which sequence of intracellular loop 2 was substituted indicated that the nature
      of amino acids in this domain may indirectly modulate A2aAR-Gs coupling.
      Replacement of the cytoplasmic tail of the A2aAR with the A1AR tail did not
      affect adenylyl cyclase stimulation. Thus, selective activation of Gs is
      predominantly dictated by the NH2-terminal segment of the third intracellular
      loop of the A2aAR.

PMID- 8995269
TI  - Synthesis and turnover of beta2-microglobulin in Ad12-transformed cells defective
      in assembly and transport of class I major histocompatibility complex molecules.
AB  - In primary embryonal fibroblasts from transgenic mice expressing H-2 genes and a
      miniature swine class I transgene (PD1), transformation with the highly oncogenic
      Ad12 results in a reduction in peptide transporter and proteasome-associated
      (LMP2 and LMP7) gene expression, and suppression in transport and cell surface
      expression of all class I antigens. The selective suppression in transport of H-2
      (but not of PD1) molecules in cells reconstituted for the expression of peptide
      transporter and LMP genes implied that an additional factor(s) is involved in the
      assembly of class I complexes. Here we show that the beta2m, H-2Db, and H-2Kb
      genes are transcribed and translated in Ad12-transformed cells. However, unlike
      normal and E1Ad5-transformed cells, in which beta2m is either secreted unbound or
      bound to class I heavy chains, in Ad12-transformed cells significant amounts of
      beta2m are retained in the cell bound to the membrane, but free of class I heavy
      chains. This abnormal turnover of beta2m in the Ad12-transformed cells suggests
      the existence of a novel beta2m-binding molecule(s) that sequesters beta2m, and
      this process may provide a mechanism by which transformation with Ad12 may
      subvert class I complex formation.

PMID- 8995270
TI  - NMR studies on the flexibility of the poliovirus C3 linear epitope inserted into
      different sites of the maltose-binding protein.
AB  - A set of permissive positions that tolerate insertions/deletions without major
      deleterious consequences for the binding activity of the protein was previously
      identified in the maltose-binding protein. The C3 epitope from poliovirus VP1
      protein (93DNPASTTNKDK103) was inserted into eight of these positions and two
      nonpermissive control sites. NMR studies were performed on the MalE protein, the
      insertion/deletion mutants, and the C3MalE hybrids to selectively determine the
      flexible regions in these proteins. Comparison of the C3 epitope mobility in the
      different hybrid proteins indicates that, whatever its insertion site and
      independently from the specific sequences of its linkers, the epitope is mostly
      flexible. The vector protein was shown to unfold partially only in the two C3MalE
      hybrids that correspond to nonpermissive positions. For one of them (insertion at
      site 339), both sides of the insert are flexible, and at most one side for all
      the other hybrids. This result correlates with the antigenicity data on the
      inserted epitope (Martineau, P., Leclerc, C., and Hofnung, M. (1997) Mol.
      Immunol, in press.

PMID- 8995271
TI  - Conserved E boxes function as part of the enhancer in hypersensitive site 2 of
      the beta-globin locus control region. Role of basic helix-loop-helix proteins.
AB  - The human beta-globin gene cluster is regulated in part by a distal locus control
      region that is required for opening a chromatin domain in erythroid cells and
      enhancing expression of the beta-like globin genes at the correct developmental
      stages. One part of the locus control region, called hypersensitive site 2 (HS2),
      functions as a strong enhancer. Matches to the consensus binding sites for basic
      helix-loop-helix (bHLH) proteins (E boxes) are well conserved within the HS2
      core. We show that mutations of the HS2 core that alter an invariant E box cause
      a 3.5-fold reduction in enhancement of expression of an epsilon-globin reporter
      gene in transiently transfected K562 cells, both before and after induction.
      Mutations of the HS2 core that alter a less-highly conserved E box cause a more
      modest reduction in enhancement. Footprint analysis shows binding of erythroid
      nuclear proteins in vitro to the invariant E box as well as an adjacent CAC/GTG
      box. Probes containing the E box regions form sequence-specific complexes with
      proteins from both K562 and MEL nuclear extracts; these are disrupted by the same
      mutations that decrease enhancement. Some of these latter complexes contain known
      bHLH proteins, as revealed by specific loss of individual complexes when treated
      with antibodies against TAL1 and USF. Interaction between the E boxes and the
      bHLH proteins, as well as other binding proteins, could account for the role of
      these sites in enhancement by HS2.

PMID- 8995273
TI  - Effect of distal cavity mutations on the binding and activation of oxygen by
      ferrous horseradish peroxidase.
AB  - Mutations have been introduced at residues Arg-38 or His-42 in horseradish
      peroxidase isoenzyme C (HRPC) in order to probe the role of these key distal
      residues in the reaction of ferrous HRPC with dioxygen. The association and
      dissociation rate constants for dioxygen binding to His-42 --> Leu, His-42 -->
      Arg, Arg-38 --> Leu, Arg-38 --> Lys, Arg-38 --> Ser, and Arg-38 --> Gly variants
      have been measured using stopped-flow spectrophotometry. Replacement of His-42 by
      Leu or Arg increases the oxygen binding rate constant by less than an order of
      magnitude, whereas changing the polar distal Arg-38 causes increases of more than
      2 orders. These results demonstrate that His-42 and Arg-38 impede the binding of
      dioxygen to ferrous HRPC, presumably by steric and/or electrostatic interactions
      in the distal heme cavity. Recombinant HRPC oxyperoxidase reverted slowly to the
      ferric state with no spectrophotometrically detectable intermediates and with an
      apparent first-order rate constant of 9.0 x 10(-3) s(-1), which is essentially
      the same as that for the native, glycosylated enzyme. This reaction was
      accelerated when His-42 was replaced by Leu or Arg (k(decay) = 0.10 and 0.07 s(
      1), respectively) presumably due to the loss of the hydrogen bond between the His
      42 imidazole and the bound dioxygen. Substitution of Arg-38 by Leu, Lys, or Gly
      also produced a less stable oxyperoxidase (k(decay) = 0.22, 0.20, and 0.58 s(-1),
      respectively). However, with the Arg-38 --> Ser variant, a transient
      intermediate, proposed to be a ferric-superoxide complex, was detected by rapid
      scan stopped-flow spectrophotometry during the conversion of oxyperoxidase to the
      ferric state. This variant also exhibits an unusually high affinity for dioxygen.
      It is proposed that Arg-38 interacts with the bound dioxygen to promote
      superoxide character, thereby stabilizing the oxyperoxidase state and making the
      binding of dioxygen to ferrous HRPC essentially irreversible. We conclude that
      Arg-38 and His-42 not only promote the heterolytic cleavage of bound hydrogen
      peroxide to form compound I but also decrease the lability of the ferrous enzyme
      dioxygen complex in order to suppress the formation of the inactive ferrous
      state.

PMID- 8995272
TI  - Identification of critical determinants for autoinhibition in the pseudosubstrate
      region of type I alpha cAMP-dependent protein kinase.
AB  - The consensus substrate site for cAMP-dependent protein kinase (PKA) is Arg-Arg
      Xaa-Ser(P)-Xaa and the autoinhibitory domain of the PKA type I alpha regulatory
      subunit (RI subunit) contains a similar sequence, Arg92-Arg-Arg-Arg-Gly-Ala-Ile
      Ser-Ala-Glu. The italicized amino acids form a putative pseudosubstrate site (Ser
      is replaced with Ala), which together with adjacent residues could competitively
      inhibit substrate phosphorylation by the PKA catalytic subunit (C subunit). The
      present studies determine the contributions of Arg92-95, Ile98, and Glu101 to
      inhibitory potency. Amino-terminal truncation of RI subunit through Arg92 (delta1
      92) or Arg93 (delta1-93) had no detectable effect on inhibition of C subunit.
      Truncation through Arg94 (delta1-94), or point mutation of Arg95 within truncated
      mutants (delta1-93.R95A or delta1-92.R95A), caused a dramatic reduction in
      inhibitory potency. Truncation through Arg95 (delta1-95) had a greater effect
      than did replacement or deletion of Arg94 or Arg95 alone. Using full-length RI
      subunit, the inhibitory potency was reduced by replacing Ile98 with Ala, Gly, or
      Gln, but not by replacing it with Val. The inhibitory potency of RI subunit was
      unchanged when Glu101 was replaced with Ala or Gln. It is concluded that Arg94,
      Arg95 and, to a lesser extent, Ile98 are vital constituents of PKA autoinhibition
      by type I alpha R subunit.

PMID- 8995274
TI  - Identification of Glu-268 as the catalytic nucleophile of human lysosomal beta
      galactosidase precursor by mass spectrometry.
AB  - Human lysosomal beta-galactosidase catalyzes the hydrolysis of beta-galactosides
      via a double displacement mechanism involving a covalent glycosyl enzyme
      intermediate. By use of the slow substrate 2,4-dinitrophenyl-2-deoxy-2-fluoro
      beta-D-galactopyranoside, a glycosyl enzyme intermediate has been trapped on the
      enzyme. This has allowed the catalytic nucleophile to be identified as Glu-268 by
      peptic and tryptic digestion of the inactivated enzyme followed by high
      performance liquid chromatography-electrospray ionization tandem mass
      spectrometry of the peptide mixture. This glutamic acid is fully conserved in a
      sequence-related family of enzymes (Family 35), consistent with its essential
      role.

PMID- 8995275
TI  - An oxidase-permease-based iron transport system in Schizosaccharomyces pombe and
      its expression in Saccharomyces cerevisiae.
AB  - Genetic studies have demonstrated that high affinity ferrous transport in
      Saccharomyces cerevisiae requires an oxidase (Fet3p) and a permease (Ftr1p).
      Using an iron-independent galactose-based expression system, we show that
      expression of these two genes can mediate high affinity ferrous iron transport,
      indicating that these two genes are not only necessary, but sufficient for high
      affinity iron transport. Schizosaccharomyces pombe also employ an oxidase
      permease system for high affinity iron transport. The S. pombe genes, fio1+
      (ferrous iron oxidase) and fip1+ (ferriferous permease), share significant
      similarity to FET3 and FTR1 from S. cerevisiae. Both fio1+ and fip1+ are
      transcriptionally regulated by iron need, and disruption of fio1+ results in a
      loss of high affinity iron transport. Expression of fio1+ alone in an S.
      cerevisiae fet3 disruption strain does not result in high affinity iron
      transport. This result indicates that the S. pombe ferroxidase, while
      functionally homologous to the S. cerevisiae ferroxidase, does not have enough
      similarity to interact with the S. cerevisiae permease. Simultaneous expression
      of both S. pombe genes, fio1+ and fip1+, in S. cerevisiae can reconstitute high
      affinity iron transport. These results demonstrate that the oxidase and permease
      are all that is required to reconstitute high affinity iron transport and suggest
      that such transport systems are found in other eukaryotes.

PMID- 8995276
TI  - Characterization of high affinity binding between laminin and the acute-phase
      protein, serum amyloid A.
AB  - Serum amyloid A isoforms, apoSAA1 and apoSAA2, are acute-phase proteins of
      unknown function and can be precursors of amyloid AA peptides (AA) found in
      animal and human amyloid deposits. These deposits are often a complication of
      chronic inflammatory disorders and are associated with a local disturbance in
      basement membrane (BM). In the course of trying to understand the pathogenesis of
      this disease laminin, a major BM glycoprotein, has been discovered to bind
      saturably, and with high affinity to murine acute-phase apoSAA. This interaction
      involves a single class of binding sites, which are ionic in nature, conformation
      dependent, and possibly involve sulfhydryls. Binding activity was significantly
      enhanced by Zn2+, an effect possibly mediated through Cys-rich zinc finger-like
      sequences on laminin. Collagen type IV also bound apoSAA but with lower affinity.
      Unexpectedly, no binding was detected for perlecan, a BM proteoglycan previously
      implicated in AA fibrillogenesis, although a low affinity interaction cannot be
      excluded. Entactin, another BM protein that functions to cross-link the BM matrix
      and is normally complexed with laminin, could inhibit laminin-apoSAA binding
      suggesting apoSAA does not bind to normal BM. Since laminin binds apoSAA with
      high affinity and has previously been shown to codeposit with AA amyloid fibrils,
      we postulate that laminin interacts with apoSAA and facilitates nucleation events
      leading to fibrillogenesis. This work also provides further support for the
      hypothesis that a disturbance in BM metabolism contributes to the genesis of
      amyloid. The specificity and avidity of the laminin-apoSAA interaction also
      implies that it may be a normal event occurring during the inflammatory process,
      which mediates one or more of the functions recently proposed for apoSAA.

PMID- 8995277
TI  - Suicide inactivation of cytochrome P450 by midchain and terminal acetylenes. A
      mechanistic study of inactivation of a plant lauric acid omega-hydroxylase.
AB  - Incubation of Vicia sativa microsomes, containing cytochrome P450-dependent
      lauric acid omega-hydroxylase (omega-LAH), with [1-(14)C]11-dodecynoic acid (11
      DDYA) generates a major metabolite characterized as 1,12-dodecandioic acid. In
      addition to time- and concentration-dependent inactivation of lauric acid and 11
      DDYA oxidation, irreversible binding of 11-DDYA (200 pmol of 11-DDYA bound/mg of
      microsomal protein) at a saturating concentration of 11-DDYA was observed. SDS
      polyacrylamide gel electrophoresis analysis showed that 30% of the label was
      associated with several protein bands of about 53 kDa. The presence of beta
      mercaptoethanol in the incubate reduces 1,12-dodecandioic acid formation and
      leads to a polar metabolite resulting from the interaction of oxidized 11-DDYA
      with the nucleophile. Although the alkylation of proteins was reduced, the lauric
      acid omega-hydroxylase activity was not restored, suggesting an active site
      directed inactivation mechanism. Similar results were obtained when reconstituted
      mixtures of cytochrome P450 from family CYP4A from rabbit liver were incubated
      with 11-DDYA. In contrast, both 11- and 10-DDYA resulted in covalent labeling of
      the cytochrome P450 2B4 protein and irreversible inhibition of activity. These
      results demonstrate that acetylenic analogues of substrate are efficient
      mechanism-based inhibitors and that a correlation between the position of the
      acetylenic bond in the inhibitor and the regiochemistry of cytochromes P450
      oxygenation is essential for enzyme inactivation.

PMID- 8995278
TI  - Spectroscopic studies of cobalt(II) binding to Escherichia coli bacterioferritin.
AB  - The iron storage protein bacterioferritin (BFR) consists of 24 identical
      subunits, each containing a dinuclear metal binding site called the ferroxidase
      center, which is essential for fast iron core formation. Cobalt(II) binding to
      wild-type and site-directed variants of Escherichia coli BFR was studied by
      optical and magnetic techniques. Data from absorption spectroscopy demonstrate
      the binding of two cobalt(II) ions per subunit of wild-type and heme-free BFR,
      each with a pseudotetrahedral or pentacoordinate geometry, and EPR studies show
      that the two cobalt(II) ions are weakly magnetically coupled. Studies of variants
      of BFR in which a single glutamic acid residue at the ferroxidase center is
      replaced by alanine confirm that this is the site of cobalt(II) binding, since
      the altered centers bind only one cobalt(II) ion. This work shows that the
      electroneutrality of the ferroxidase center is preserved on binding a pair of
      divalent metal ions. Optical and EPR data show that cobalt(II) binding to BFR
      exhibits positive cooperativity, with an average Kd of approximately 1 x 10(-5)
      M. The favored filling of the ferroxidase center with pairs of metal ions may
      have mechanistic implications for the iron(II) binding process. Discrimination
      against oxidation of single iron(II) ions avoids odd electron reduction products
      of oxygen.

PMID- 8995279
TI  - Replication protein A. Characterization and crystallization of the DNA binding
      domain.
AB  - Replication protein A (RPA) is a heterotrimeric single-stranded DNA-binding
      protein in eukaryotic cells. The DNA binding activity of human RPA has been
      previously localized to the N-terminal 441 amino acids of the 70-kDa subunit,
      RPA70. We have used a combination of limited proteolysis and mutational analysis
      to define the smallest soluble fragment of human RPA70 that retains complete DNA
      binding activity. This fragment comprises residues 181-422. RPA181-422 bound DNA
      with the same affinity as the 1-441 fragment and had a DNA binding site of 8
      nucleotides or less. RPA70 fragments were subjected to crystal trials in the
      presence of single-stranded DNA, and diffraction quality crystals were obtained
      for RPA181-422 bound to octadeoxycytidine. The RPA181-422 co-crystals belonged to
      the P2(1)2(1)2(1) space group, with unit cell dimensions of a = 34.3 A, b = 78.0
      A, and c = 95.4 A and diffracted to a resolution of 2.1 A.

PMID- 8995280
TI  - Molecular identification of a novel fibrinogen binding site on the first domain
      of ICAM-1 regulating leukocyte-endothelium bridging.
AB  - Binding of fibrinogen to intercellular adhesion molecule 1 (ICAM-1) enhances
      leukocyte adhesion to endothelium by acting as a bridging molecule between the
      two cell types. Here, a panel of four monoclonal antibodies (mAbs) to ICAM-1 was
      used to dissect the structure-function requirements of this recognition. All four
      mAbs bound to ICAM-1 transfectants and immunoprecipitated and immunoblotted ICAM
      1 from detergent-solubilized JY lymphocyte extracts. Functionally, mAbs 1G12 and
      2D5 inhibited binding of 125I-fibrinogen to ICAM-1-transfectants and abrogated
      the enhancing effect of fibrinogen on mononuclear cell adhesion to endothelium
      and transendothelial migration. In contrast, mAbs 3D6 and 6E6 did not affect ICAM
      1 recognition of fibrinogen. With respect to other ligands, mAbs 1G12 and 2D5
      completely inhibited attachment of Plasmodium falciparum-infected erythrocytes to
      immobilized recombinant ICAM-1-Fc, whereas they had no effect on LFA-1-dependent
      T cell binding to ICAM-1-Fc. Conversely, mAbs 3D6 and 6E6 completely abolished
      LFA-1 binding to ICAM-1-Fc. Epitope assignment using ICAM-1 chimeras and receptor
      mutants revealed that the fibrinogen-blocking mAbs 1G12 and 2D5 reacted with
      domain 1 of ICAM-1, and their binding was disrupted by 97 and 70% by mutations of
      D26 and P70, respectively, whereas mAbs 3D6 and 6E6 bound to domain 2 of ICAM-1.
      By recognizing a site distinct from that of beta2 integrins Mac-1 or LFA-1,
      fibrinogen binding to ICAM-1 may provide an alternative pathway of intercellular
      adhesion and/or modulate integrin-dependent adherence during inflammation and
      vascular injury.

PMID- 8995281
TI  - Changes in cyclin-dependent kinase 2 and p27kip1 accompany glial cell
      differentiation of central glia-4 cells.
AB  - The generation of different glial cell types in the central nervous system
      depends upon a wide variety of proliferative and differentiative signals. Here we
      report that changes in the levels of cyclin-dependent kinase 2 (CDK2) and the
      cell cycle inhibitor p27kip1 accompany the differentiation of central glia-4 (CG
      4) progenitor cells to an astrocytic cell phenotype in the presence of fetal calf
      serum. Although a decrease in CDK2 levels was observed in both oligodendrocyte
      and astrocyte cells derived from CG-4 cells, a striking increase in the levels of
      p27 was observed during the differentiation of astrocyte cells. In astrocyte cell
      extracts, inhibition of CDK2 activity could be overcome with exogenously added
      cyclin E. Furthermore, depletion of p27 from astrocyte extracts lowered the
      amount of cyclin E required for CDK2 activation. Taken together, these results
      suggest that the inhibitory action of p27 upon cyclin E-CDK2 may prevent entry of
      cells into the S phase and regulate the progression of CG-4 cells toward an
      astrocytic lineage.

PMID- 8995282
TI  - Functional association between the insulin receptor and the transmembrane protein
      tyrosine phosphatase LAR in intact cells.
AB  - The receptor-type protein-tyrosine phosphatase LAR (for leukocyte common antigen
      related) has been implicated as a physiological regulator of the insulin
      receptor. To demonstrate a functional interaction between LAR and the insulin
      receptor, we incubated CHO cells overexpressing the human insulin receptor with
      an antibody to the extracellular domain of LAR and found a 47% decrease in
      insulin receptor autophosphorylation and kinase activity. A physical association
      between LAR and the insulin receptor was then shown by immunoprecipitation of LAR
      from cell lysates and immunoblotting with antibody to the insulin receptor, or
      vice versa. Up to 11.8% of the LAR protein in the lysates of CHO cells
      overexpressing both the insulin receptor and LAR co-immunoprecipitated with the
      insulin receptor. The LAR/insulin receptor association was related to the level
      of LAR or insulin receptor overexpression and was increased 6.5-fold by chemical
      cross-linking and 3.9-fold by treatment with insulin, suggesting that receptor
      activation influences the affinity of LAR for the insulin receptor. In insulin
      stimulated rat liver, LAR was temporally enriched in endosomes with the insulin
      receptor, and incubation of endosomes with neutralizing LAR antibodies decreased
      insulin receptor dephosphorylation in situ by 28% (p = 0.01 versus control).
      These data provide more direct evidence of a role for LAR in the physiological
      regulation of insulin action at the receptor level.

PMID- 8995283
TI  - Identification of His141 in the active site of Bacillus subtilis adenylosuccinate
      lyase by affinity labeling with 6-(4-bromo-2,3-dioxobutyl)thioadenosine 5'
      monophosphate.
AB  - Adenylosuccinate lyase of Bacillus subtilis is inactivated by 25-400 microM 6-(4
      bromo-2,3-dioxobutyl)thioadenosine 5'-monophosphate (6-BDB-TAMP) at pH 7.0 and 25
      degrees C. The initial inactivation rate constant exhibits nonlinear dependence
      on the concentration of 6-BDB-TAMP, implying there is reversible formation of
      enzyme-reagent complex (K(I) = 30 +/- 4 microM) prior to irreversible
      modification (kmax = 0.139 +/- 0.005 min(-1)). The tetrameric enzyme incorporates
      about 1 mol of 6-BDB-[32P]TAMP per mol of enzyme subunit concomitant with
      complete inactivation. Protection against inactivation and incorporation of
      [32P]reagent is provided by adenylosuccinate or a combination of AMP and
      fumarate, whereas either AMP or fumarate alone is much less effective. These
      observations suggest that 6-BDB-TAMP targets the adenylosuccinate-binding site.
      Hydrolyzed 6-BDB-TAMP is a competitive inhibitor with respect to adenylosuccinate
      in the catalytic reaction and also decreases the rate of inactivation by 6-BDB
      TAMP. These results account for the decrease in the inactivation rate as the
      reaction of 6-BDB-TAMP with the enzyme proceeds. Purification by chromatography
      on dihydroxyboryl-agarose and high performance liquid chromatography of the
      tryptic digest of inactivated enzyme yields a single radioactive peptide, Thr140
      Phe150, as determined by gas-phase sequencing. Modified His141 is the reaction
      product of 6-BDB-TAMP and adenylosuccinate lyase. We conclude that 6-BDB-TAMP
      functions as a reactive adenylosuccinate analog in modifying His141 in the
      substrate-binding site of adenylosuccinate lyase, where it may serve as a general
      base accepting a proton from the succinyl group during catalysis.

PMID- 8995284
TI  - Selective recognition of phosphatidylinositol 3,4,5-trisphosphate by a synthetic
      peptide.
AB  - The present study takes a novel approach to explore the mode of action of
      phosphoinositide 3-kinase lipid products by identifying a synthetic peptide W
      NG(28-43) (WAAKIQASFRGHMARKK) that displays discriminative affinity with
      phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). This PtdIns(3,4,5)P3
      binding peptide was discovered by a gel filtration-based binding assay and
      exhibits a high degree of stereochemical selectivity in phosphoinositide
      recognition. It forms a 1:1 complex with PtdIns(3,4,5)P3 with Kd of 2 microM, but
      binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and
      phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) with substantially lower
      affinity (5- and 40-fold, respectively) despite the largely shared structural
      motifs with PtdIns(3,4,5)P3. Other phospholipids examined, including
      phosphatidylserine, phosphatidylcholine, phosphatidylinositol, and
      phosphatidylethanolamine, show low or negligible affinity with the peptide.
      Several lines of evidence indicate that this phosphoinositide-peptide interaction
      is not due to nonspecific electrostatic interactions or phospholipid aggregation,
      and requires a cooperative action among the hydrophobic and basic residues to
      exert the selective recognition. CD data suggest that the peptide acquires an
      ordered structure upon binding to PtdIns(3,4,5)P3. Further, we demonstrate that
      PtdIns(3,4,5)P3 enhances the phosphorylation rate of this binding peptide by
      protein kinase C (PKC)-alpha in a dose-dependent manner. In view of the findings
      that this stimulatory effect is not noted with other PKC peptide substrates
      lacking affinity with PtdIns(3,4,5)P3 and that PKC-alpha is not susceptible to
      PtdIns(3,4,5)P3 activation, the activity enhancement is thought to result from
      the substrate-concentrating effect of the D-3 phosphoinositide, i.e. the presence
      of PtdIns(3,4,5)P3 allows the peptide to bind to the same vesicles/micelles to
      which PKC is bound. Moreover, it is noteworthy that neurogranin, the full-length
      protein of W-NG(28-43) and a relevant PKC substrate in the forebrain, binds
      PtdIns(3,4,5)P3 with high affinity. Taken together, it is plausible that, in
      addition to PKC activation, PtdIns(3,4,5)P3 provides an alternative mechanism to
      regulate PKC activity in vivo by recruiting and concentrating its target proteins
      at the interface to facilitate the subsequent PKC phosphorylation.

PMID- 8995285
TI  - Purification of human double-stranded RNA-specific editase 1 (hRED1) involved in
      editing of brain glutamate receptor B pre-mRNA.
AB  - RNAs encoding subunits of glutamate-gated ion channel receptors are
      posttranscriptionally modified by RNA editing and alternative splicing. The
      change in amino acid sequence caused by RNA editing can affect both the kinetics
      and the permeability of the ion channel receptors to cations. Here, we report the
      purification of a 90-kDa double-stranded RNA-specific adenosine deaminase from
      HeLa cell nuclear extract that specifically edits the glutamine codon at position
      586 in the pre-mRNA of the glutamate receptor B subunit. Site-specific
      deamination of an adenosine to an inosine converts the glutamine codon to that of
      arginine. Recently, a gene encoding a double-stranded-specific editase (RED1) was
      cloned from a rat brain cDNA library. Antibodies generated against the deaminase
      domain of its human homolog specifically recognized and inhibited the activity of
      the 90-kDa enzyme, indicating that we have purified hRED1 the human homolog of
      rat RED1. This enzyme is distinct from double-stranded RNA-specific adenosine
      deaminase which we and others have previously purified and cloned.

PMID- 8995286
TI  - Biosynthesis of teichuronic acid in the bacterial cell wall. Purification and
      characterization of the glucosyltransferase of Micrococcus luteus.
AB  - This report describes what is, to our knowledge, the first purification to near
      homogeneity of an enzyme involved in the biosynthesis of the teichuronic acid of
      Micrococcus luteus cell walls. The glucosyltransferase of M. luteus, which
      participates in the biosynthesis of teichuronic acid, was solubilized from
      cytoplasmic membrane fragments by extraction with buffer solutions containing the
      detergents Thesit (dodecyl alcohol polyoxyethylene ether; 1 mg/ml) and 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate (0.5 mg/ml). The detergent
      solubilized enzyme was purified 150-fold, with a recovery of 13% by adsorbent
      column chromatography, ion-exchange chromatography, gel filtration, and
      preparative nondenaturing gradient polyacrylamide gel electrophoresis. On the
      basis of its mobility on native gradient gel, the glucosyltransferase was
      estimated to have a molecular mass of 440 kDa. The purified native enzyme was a
      multisubunit protein consisting of subunits of two sizes; their molecular masses
      were determined to be 52.5 and 54 kDa, respectively, by observation of the
      mobility of the protein bands in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The isoelectric point of the enzyme was approximately 5.

PMID- 8995287
TI  - Heat stress induces a glycosylation of membrane sterol in myxoamoebae of a true
      slime mold, Physarum polycephalum.
AB  - To know the very early events occurring after heat shock, the changes of membrane
      lipids were examined. Heat stress induced the production of a certain glycolipid
      in the myxoamoebae of Physarum polycephalum in a few minutes. The purified
      glycolipid was determined to be a poriferasterol monoglucoside by structural
      studies that was previously reported to be expressed during the differentiation
      of Physarum cells from haploid myxoamoebae to diploid plasmodia (Murakami
      Murofushi, K., Nakamura, K., Ohta, J., Suzuki, M., Suzuki, A., Murofushi, H., and
      Yokota, T. (1987) J. Biol. Chem. 262, 16719-16723). The activity of UDP
      glucose:poriferasterol glucosyltransferase (Murakami-Murofushi, K., and Ohta, J.
      (1989) Biochim. Biophys. Acta 992, 412-415) was also expressed rapidly after heat
      shock. Thus, the activation of sterol glucosyltransferase and the production of
      sterol-glucoside were considered to be important events that were involved in the
      signal transduction system to induce some succeeding heat-shock responses, such
      as the synthesis of heat-shock proteins.

PMID- 8995288
TI  - DNA distortion and base flipping by the EcoRV DNA methyltransferase. A study
      using interference at dA and T bases and modified deoxynucleosides.
AB  - The EcoRV DNA methyltransferase introduces a CH3 group at the 6-amino position of
      the first dA in the duplex sequence d(GATATC). It has previously been reported
      that the methylase contacts the four phosphates (pNpNpGpA) at, and preceding, the
      5'-end of the recognition sequence as well as the single dG in this sequence
      (Szczelkun, M. D., Jones, H., and Connolly, B. A. (1995) Biochemistry 34, 10734
      10743). To study the possible role of the dA and T bases within the ATAT
      sequence, interference studies have been carried out using diethylpyrocarbonate
      and osmium tetroxide. The methylase bound very strongly to hemimethylated
      oligonucleotides modified at the second AT, of the ATAT sequence, in the
      unmethylated strand of the duplex. This probably arises because these
      modifications facilitate DNA distortion that follows the binding of the nucleic
      acid to the protein. Oligonucleotides containing modified bases at both the
      target dA base and its complementary T were used to determine whether this dA
      methylase flips out its target base in a similar manner to that observed for dC
      DNA methylases. In binary EcoRV methylase-DNA complexes, analogues that weakened
      the base pair caused an increase in affinity between the protein and the nucleic
      acid. In contrast, in ternary EcoRV methylase-DNA-sinefungin (an analogue of the
      natural co-factor, S-adenosyl-L-methionine (AdoMet)) complexes, only small
      differences in affinity were observed between the normal dA-T base pair and the
      analogues. These results are almost identical to those seen with DNA dC
      methylases (Klimasauskas, S., and Roberts R. J. (1995) Nucleic Acid Res. 23, 1388
      1395; Yang, S. A., Jiang-Cheng, S., Zingg, J. M., Mi, S., and Jones, P. A. (1995)
      Nucleic Acids Res. 23, 1380-1387) and support a base-flipping mechanism for DNA
      dA methylases.

PMID- 8995289
TI  - Up-regulation of the alpha2-macroglobulin signaling receptor on rheumatoid
      synovial fibroblasts.
AB  - In the present study, we demonstrate that the alpha2-macroglobulin (alpha2M)
      signaling receptor is up-regulated on rheumatoid synovial fibroblasts. In
      rheumatoid cells, 125I-alpha2M-methylamine bound to two sites; namely, one of
      high affinity (Kd approximately 52 pM) and the second of lower affinity (Kd
      approximately 9.7 nM). In normal synovial fibroblasts only one site for 125I
      alpha2M-methylamine (Kd approximately 5.36 nM) was present. Receptor-associated
      protein did not inhibit the binding of alpha2M-methylamine to the high affinity
      binding sites, but it caused a 70-80% reduction in its binding to low affinity
      binding sites establishing its identity as the low density lipoprotein receptor
      related protein/alpha2M receptor. Binding of alpha2M-methylamine to rheumatoid
      but not normal synovial fibroblasts caused a rapid rise in inositol 1,4,5
      trisphosphate synthesis with a peak reached within 10 s of ligand exposure.
      Concomitantly, rheumatoid but not normal cells showed a rise in intracellular
      Ca2+. Pretreatment of rheumatoid cells with Receptor-associated protein or
      pertussis toxin did not affect the alpha2M-methylamine-induced increase in
      intracellular Ca2+. These are characteristic properties of ligation by alpha2M
      methylamine of the alpha2M signaling receptor but not the lipoprotein receptor
      related protein/alpha2M receptor. Binding of alpha2M-methylamine to rheumatoid
      synovial fibroblasts significantly increased the synthesis of DNA compared with
      normal synovial fibroblasts treated similarly.

PMID- 8995290
TI  - Functional analysis of microphthalmia-associated transcription factor in pigment
      cell-specific transcription of the human tyrosinase family genes.
AB  - Tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2 are the enzymes
      involved in melanin biosynthesis and are preferentially expressed in pigment
      cells. Their human gene promoters share the 11-base pair M box containing a
      CATGTG motif, which was shown here to be bound in vitro by microphthalmia
      associated transcription factor (MITF). Transient cotransfection analysis showed
      that MITF overexpression increased the expression of a reporter gene under the
      control of the human tyrosinase or TRP-1 gene promoter but not the TRP-2
      promoter. The promoter activation caused by MITF is dependent on each CATGTG
      motif of the distal enhancer element, the M box, and the initiator E box of the
      tyrosinase gene and the TRP-1 M box. Furthermore, a truncated MITF lacking the
      carboxyl-terminal 125 amino acid residues transactivated the tyrosinase promoter
      less efficiently than did MITF, suggesting that MITF's carboxyl terminus contains
      a transcriptional activation domain, but unexpectedly such a truncated MITF
      remarkably transactivated the TRP-2 gene promoter. These results suggest that
      MITF is sufficient to direct pigment cell-specific transcription of the
      tyrosinase and TRP-1 genes but not the TRP-2 gene.

PMID- 8995291
TI  - Folding and stability of the Z and S(iiyama) genetic variants of human alpha1
      antitrypsin.
AB  - Z (Glu342 --> Lys) and S(iiyama) (Ser53 --> Phe) genetic variations of human
      alpha1-antitrypsin (alpha1-AT) cause a secretion blockage in the hepatocytes,
      leading to alpha1-AT deficiency in the plasma. Using in vitro folding analysis,
      we have shown previously that these mutations interfere with the proper folding
      of polypeptides. To understand the fundamental cause for the secretion defect of
      the Z and S(iiyama) variants of alpha1-AT, we investigated in vivo folding and
      stability of these variant alpha1-AT using the secretion system of yeast
      Saccharomyces cerevisiae. Various thermostable mutations suppressing the folding
      block of the Z variant in vitro corrected the secretion defect as well as the
      intracellular degradation in the yeast secretion system. Significantly, the
      extent of suppression in the secretion defect of Z protein was proportional to
      the extent of suppression in the folding defect, assuring that the in vivo defect
      associated with the Z variant is primarily derived from the folding block. In
      contrast, the folding and secretion efficiency of S(iiyama) was not much improved
      by the same mutations. In addition, none of the rarely secreted S(iiyama) alpha1
      AT carrying the stabilizing mutations for the wild type and Z variant were
      active. It appears that the major defect in S(iiyama) variant is the loss of
      stability in contrast to the kinetic block of folding in the Z variant.

PMID- 8995292
TI  - Spectral demonstration of semihemoglobin formation during CN-hemin incorporation
      into human apohemoglobins.
AB  - The incorporation of CN-hemin into three human adult apohemoglobin species
      (apohemoglobin, alpha-apohemoglobin, and apohemoglobin modified at its beta93
      sulfhydryl with p-hydroxymercuribenzoate) has been monitored at micromolar
      concentrations in 0.05 M potassium phosphate buffer, pH 7.0, at 10 degrees C. In
      all cases, Soret spectral blue shifts accompanied CN-protohemoglobin but not CN
      deuterohemoglobin formation. This finding in conjunction with isofocusing studies
      provided evidence of a CN-protosemi-alpha-hemoglobin intermediate, the formation
      of which appeared to be a direct consequence of CN-protohemin-alpha heme pocket
      interactions. The kinetics of full reconstitution of CN-protohemoglobin and CN
      deuterohemoglobin revealed four distinct phases that apparently correlated with
      heme insertion (Phase I), local structural rearrangement (Phase II), global
      conformational response (Phase III), and irreversible histidine iron bond
      formation (Phase IV). These phases exhibited rates of 7.8-22 x 10(7) M(-1) s(-1),
      0.19-0.23 s(-1), 0.085-0.12 s(-1), and 0.008-0.012 s(-1), respectively. Partial
      (50%) reconstitution with CN-protohemin, in contrast, revealed only three kinetic
      phases (with Phase III missing) of heme incorporation into native and p
      hydroxymercuribenzoate-modified apohemoglobin. Furthermore, the absence of Phase
      III slowed the rate of proximal bond formation. These findings support the
      premise that irreversible assembly of CN-protosemi-alpha-hemoglobin is deterred
      by the presence of a heme-free beta partner, the consequence of which may be that
      intermolecular heme transfer is encouraged under conditions of heme deficiency in
      vivo.

PMID- 8995293
TI  - An effector-like function of Ras GTPase-activating protein predominates in
      cardiac muscle cells.
AB  - In contrast to familiar role for Ras in proliferation, we and others previously
      suggested that Ras also mediates hypertrophy, the increase in cell mass
      characteristic of post-natal ventricular muscle. We showed that activated (G12R)
      and dominant-negative (S17N) Ha-Ras regulate "constitutive" and growth factor
      responsive genes equivalently, in both cardiac myocytes and non-cardiac, Mv1Lu
      cells. Here, we attempt to delineate pathways by which Ras exerts this global
      effect. The E63K mutation, which impairs binding of guanine nucleotide releasing
      factor to Ras, alleviated suppression by S17N, consistent with sequestration of
      exchange factors as the mechanism for inhibition. To compare potential Ras
      effector proteins, we first engineered G12R/D38N, to abolish binding of Raf and
      phosphatidylinositol-3-kinase and established that this site was indispensable
      for augmenting gene expression. To distinguish between inhibition of Ras by Ras
      GTPase-activating protein (GAP) versus a potential effector function of GAP, we
      tested the effector domain substitution P34R: this mutation, which abolishes GAP
      binding, enhanced Ras-dependent transcription in Mv1Lu cells, yet interfered with
      Ras-dependent expression in ventricular myocytes. To examine the dichotomous role
      of Ras-GAP predicted from these P34R results, we transfected both cell types with
      full-length GAP, the C-terminal catalytic domain (cGAP), or N-terminal Src
      homology domains (nGAP). In Mv1Lu cells, cGAP markedly inhibited both reporter
      genes, whereas GAP and nGAP had little effect. Antithetically, in ventricular
      myocytes, GAP and nGAP activated gene expression, whereas cGAP was ineffective.
      Thus, Ras activates gene expression through differing effectors contingent on
      cell type, and an effector-like function of GAP predominates in ventricular
      muscle.

PMID- 8995294
TI  - Bacterial protease Lon is a site-specific DNA-binding protein.
AB  - The product of the Escherichia coli lon gene is the ATP-dependent Lon protease.
      Lon contributes to the regulation of several important cellular functions,
      including radiation resistance, cell division, filamentation, capsular
      polysaccharide production, lysogeny of certain bacteriophages, and proteolytic
      degradation of certain regulatory and abnormal proteins. Lon homologues are also
      found in several widely divergent bacteria, as well as in the mitochondria of
      yeast and humans. E. coli Lon has long been known to bind to DNA, but this
      interaction has not been further characterized and has generally been assumed to
      be nonspecific. We now demonstrate that E. coli Lon can bind to a TG-rich DNA
      promoter element in a sequence-specific manner. This finding is based on the
      results of experiments employing SouthWestern blotting, protein purification,
      "shift-shift" electrophoretic mobility shift assays, electrophoretic mobility
      shift assays using in vitro transcribed and translated Lon, and DNase
      footprinting. Site-specific DNA binding is likely to be an additional important
      biochemical characteristic of the multifaceted Lon protease.

PMID- 8995295
TI  - Functional domains of the nuclear receptor hepatocyte nuclear factor 4.
AB  - The hepatocyte nuclear factor 4 (HNF-4) is a member of the nuclear receptor
      superfamily and participates in the regulation of several genes involved in
      diverse metabolic pathways and developmental processes. To date, the functional
      domains of this nuclear receptor have not been identified, and it is not known
      whether its transcriptional activity is regulated by a ligand or other signals.
      In this report, we show that HNF-4 contains two transactivation domains,
      designated AF-1 and AF-2, which activate transcription in a cell type-independent
      manner. AF-1 consists of the extreme N-terminal 24 amino acids and functions as a
      constitutive autonomous activator of transcription. This short transactivator
      belongs to the class of acidic activators, and it is predicted to adopt an
      amphipathic alpha-helical structure. In contrast, the AF-2 transactivator is
      complex, spanning the 128-366 region of HNF-4, and it cannot be further dissected
      without impairing activity. The 360-366 region of HNF-4 contains a motif that is
      highly conserved among transcriptionally active nuclear receptors, and it is
      essential for AF-2 activity, but it is not necessary for dimerization and DNA
      binding of HNF-4. Thus, HNF-4 deletion mutants lacking the 361-465 region bind
      efficiently to DNA as homo- and heterodimers and behave as dominant negative
      mutants. Remarkably, the full transactivation potential of AF-2 is inhibited by
      the region spanning residues 371-465 (region F). The inhibitory effect of region
      F on the HNF-4 AF-2 activity is a unique feature among members of the nuclear
      receptor superfamily, and we propose that it defines a distinct regulatory
      mechanism of transcriptional activation by HNF-4.

PMID- 8995296
TI  - Ran-binding protein 1 (RanBP1) forms a ternary complex with Ran and karyopherin
      beta and reduces Ran GTPase-activating protein (RanGAP) inhibition by karyopherin
      beta.
AB  - The nuclear accumulation of proteins containing nuclear localization signals
      requires the Ran GTPase and a complex of proteins assembled at the nuclear pore.
      RanBP1 is a cytosolic Ran-binding protein that inhibits RCC1-stimulated release
      of GTP from Ran. RanBP1 also promotes the binding of Ran to karyopherin beta
      (also called importin beta and p97) and is a co-stimulator of RanGAP activity.
      Yeast karyopherin beta inhibits the GTP hydrolysis by Ran catalyzed by RanGAP. To
      further define the roles of RanBP1 and karyopherin beta in Ran function, we
      explored the effects of RanBP1 and karyopherin beta on mammalian proteins known
      to regulate Ran. Like RanBP1, karyopherin beta prevented the release of GTP from
      Ran stimulated by RCC1 or EDTA. As with the yeast protein, mammalian karyopherin
      beta completely blocked RanGAP activity. However, the addition of RanBP1 to this
      assay partially rescued the inhibited RanGAP activity. Kinetic analysis of the
      effects on RanGAP activity by karyopherin beta and RanBP1 revealed a combination
      of competitive and noncompetitive interactions. Solution binding assays confirmed
      the ability of RanBP1 to associate with Ran and karyopherin beta in a ternary
      complex, and RanBP1 binding was not competed out by the addition of karyopherin
      beta. These results demonstrate that RanBP1 and karyopherin beta interact with
      distinct sites of Ran and suggest that RanBP1 plays an essential role in nuclear
      transport by permitting RanGAP-mediated hydrolysis of GTP on Ran complexed to
      karyopherin beta.

PMID- 8995297
TI  - Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin
      family protein with thrombospondin motifs as an inflammation associated gene.
AB  - A cellular disintegrin and metalloproteinase (ADAM) is a new family of genes with
      structural homology to the snake venom metalloproteinases and disintegrins. We
      screened genes which were selectively expressed in the cachexigenic colon 26
      adenocarcinoma subline in vivo. It was found that one novel cDNA clone,
      identified as a cachexigenic tumor selective gene, encodes a cysteine-rich
      protein which shows a sequence similarity to that of both the snake venom
      metalloproteinases and thrombospondins. We named this cDNA clone A disintegrin
      and metalloproteinase with thrombospondin motifs (ADAMTS-1). ADAMTS1 consists of
      six domains, 1) a pro- and 2) a metalloproteinase, 3) a disintegrin-like, 4) a
      thrombospondin (TSP) homologous domain containing TSP type I motif, 5) a spacer
      region, and 6) COOH-terminal TSP submotifs. Unlike other ADAMs, ADAMTS-1 does not
      possess a transmembrane domain and is a putative secretory protein. Therefore,
      ADAMTS-1 is a new type of ADAM family protein with TSP type I motifs. We
      demonstrated that the TSP homologous domain containing the TSP type I motif of
      ADAMTS-1 is functional for binding to heparin. ADAMTS-1 mRNA could be induced by
      stimulating colon 26 cells with an inflammatory cytokine, interleukin-1, in
      vitro. Moreover, intravenous administration of lipopolysaccharide in mice
      selectively induced ADAMTS-1 mRNA in kidney and heart. These data suggest that
      ADAM-TS-1 may be a gene whose expression is associated with various inflammatory
      processes as well as development of cancer cachexia.

PMID- 8995299
TI  - A point mutation in Escherichia coli DNA helicase II renders the enzyme
      nonfunctional in two DNA repair pathways. Evidence for initiation of unwinding
      from a nick in vivo.
AB  - Biosynthetic errors and DNA damage introduce mismatches and lesions in DNA that
      can lead to mutations. These abnormalities are susceptible to correction by a
      number of DNA repair mechanisms, each of which requires a distinct set of
      proteins. Escherichia coli DNA helicase II has been demonstrated to function in
      two DNA repair pathways, methyl-directed mismatch repair and UvrABC-mediated
      nucleotide excision repair. To define further the role of UvrD in DNA repair a
      site-specific mutant was characterized. The mutation, uvrDQ251E, resides within
      helicase motif III, a conserved segment of amino acid homology found in a
      superfamily of prokaryotic and eukaryotic DNA helicases. The UvrD-Q251E protein
      failed to complement the mutator and ultraviolet light-sensitive phenotypes of a
      uvrD deletion strain indicating that the mutant protein is inactive in both
      mismatch repair and excision repair. Biochemical characterization revealed a
      significant defect in the ability of the mutant enzyme to initiate unwinding at a
      nick. The elongation phase of the unwinding reaction was nearly normal. Together,
      the biochemical and genetic data provide evidence that UvrD-Q251E is
      dysfunctional because the mutant protein fails to initiate unwinding at the
      nick(s) used to initiate excision and subsequent repair synthesis. These results
      provide direct evidence to support the notion that helicase II initiates
      unwinding from a nick in vivo in mismatch repair and excision repair.

PMID- 8995298
TI  - Differences between plant and animal Myb domains are fundamental for DNA binding
      activity, and chimeric Myb domains have novel DNA binding specificities.
AB  - Several Myb domain proteins have been identified in plants, in which they play
      important regulatory roles in specific cellular processes. Plant and animal Myb
      domains have significant differences, but how these differences are important for
      function is not yet understood. The P gene encodes a Myb domain protein that
      activates a subset of flavonoid biosynthetic genes in maize floral organs. P and
      v-Myb bind different DNA sequences in vitro. Here we show that the Myb domain is
      solely responsible for the sequence-specific DNA binding activity of P, which
      binds DNA only in the reduced state. Differences in the DNA binding domains of v
      Myb and P, which are conserved among animal and plant Myb domains, are
      fundamental for the high affinity DNA binding activity of these proteins to the
      corresponding binding sites but are not sufficient for the distinct DNA binding
      specificities of P and v-Myb. We conclude that significant structural differences
      distinguish plant from animal Myb domains. A chimeric Myb domain with a novel DNA
      binding specificity was created by combining Myb repeats of P and v-Myb. This
      approach could be used to artificially create novel Myb domains and to target
      transcription factors to genes containing specific promoters or to modify Myb
      mediated interactions with other cellular factors.

PMID- 8995300
TI  - Membrane topology of the transposon 10-encoded metal-tetracycline/H+ antiporter
      as studied by site-directed chemical labeling.
AB  - The transposon (Tn) 10-encoded metal-tetracycline/H+ antiporter (Tn10-TetA) is
      predicted to have a membrane topology involving 12 transmembrane domains on the
      basis of the hydropathy profile of its sequence and the results of limited
      proteolysis; however, the experimental results of limited proteolysis are not
      enough to confirm the topology because proteases cannot gain access from the
      periplasmic side (Eckert, B., and Beck, C. F. (1989) J. Biol. Chem. 264, 11663
      11670). One or two cysteine residues were introduced into each predicted
      hydrophilic loop or the N-terminal segment of Tn10-TetA by site-directed
      mutagenesis, and then the topology of the protein was determined by examining
      whether labeling of the introduced Cys residue by membrane-permeant [14C]N
      ethylmaleimide ([14C]NEM) was prevented by preincubation of intact cells with the
      membrane-impermeant maleimide, 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic
      acid (AMS). The binding of [14C]NEM to the S36C (loop 1-2), L97C (loop 3-4),
      S156C (loop 5-6), R238C (loop 7-8), S296C (loop 9-10), Y357C, and D365C (loop 10
      11) mutants was completely blocked by pretreatment with AMS, indicating that
      these residues are located on the periplasmic surface. In contrast, [14C]NEM
      binding to the S4C (N-terminal segment), S65C (loop 2-3), D120C (loop 4-5), S199C
      and S201C (loop 6-7), T270C (loop 8-9), and S328C (loop 10-11) mutants was not
      affected by pretreatment with AMS, indicating that these residues are on the
      cytoplasmic surface. These results for the first time thoroughly confirm the 12
      transmembrane topology of the metal-tetracycline/H+ antiporter.

PMID- 8995301
TI  - Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium
      channel homologs from human kidney (Kir1.2 and Kir1.3).
AB  - The DNA sequence encoding the rat brain inward rectifier-10 K+ channel was
      amplified from rat brain RNA using reverse transcription-polymerase chain
      reaction and used to clone the human homolog. Low stringency screening of a human
      kidney cDNA library and subsequent DNA sequence analysis identified two related
      K+ inward rectifier cDNAs, referred to as Kir1.2 and Kir1.3, which were derived
      from transcription of distinct human genes. Kir1.2 represents the human homolog
      of the rat BIRK-10 sequence, whereas Kir1.3 was unique compared with all
      available sequence data bases. The genes that encode Kir1.2 and Kir1.3 were
      mapped to human chromosomes 1 and 21, respectively. Both genes showed tissue
      specific expression when analyzed by Northern blots. Kir1.2 was only detected in
      brain >> kidney and was detected at high levels in all brain regions examined.
      Kir1.3 was most readily detected in kidney and was also expressed in pancreas >
      lung. Comparative analysis of the predicted amino acid sequences for Kir1.2 and
      Kir1.3 revealed they were 62% identical. The most remarkable difference between
      the two polypeptides is that the Walker Type A consensus binding motif present in
      both Kir1.1 and Kir1.2 was not conserved in the Kir1.3 sequence. Expression of
      the Kir1.2 polypeptide in Xenopus oocytes resulted in the synthesis of a K+
      selective channel that exhibited an inwardly rectifying current-voltage
      relationship and was inhibited by external Ba2+ and Cs+. Kir1.2 current amplitude
      was reduced by >85% when the pH was decreased from pH 7.4 to 5.9 using the
      membrane-permeant buffer acetate but was relatively unaffected when pH was
      similarly lowered using membrane-impermeant biphthalate. The inhibition by
      intracellular protons was voltage-independent with an IC50 of pH 6.2 and a Hill
      coefficient of 1.9, suggesting the cooperative binding of 2 protons to the
      intracellular face of the channel. In contrast, Kir1.3 expression in Xenopus
      oocytes was not detectable despite the fact that the cRNA efficiently directed
      the synthesis of a polypeptide of the expected Mr in an in vitro translation
      system. Co-expression of Kir1.3 with either Kir1.1 or Kir1.2 reduced currents
      resulting from expression of these inward-rectifier subunits alone, consistent
      with a dominant negative influence on Kir1.1 and Kir1.2 expression.

PMID- 8995302
TI  - Expression of the cystic fibrosis phenotype in a renal amphibian epithelial cell
      line.
AB  - Mutations in a Cl- channel (cystic fibrosis transmembrane conductance regulator
      or CFTR) are responsible for the cystic fibrosis (CF) phenotype. Increased Na+
      transport rates are observed in CF airway epithelium, and recent studies suggest
      that this is due to an increase in Na+ channel open probability (Po). The Xenopus
      renal epithelial cell line, A6, expresses both cAMP-activated 8-picosiemen (pS)
      Cl- channels and amiloride-sensitive 4-pS Na+ channels, and provides a model
      system for examining the interactions of CFTR and epithelial Na+ channels. A6
      cells express CFTR mRNA, as demonstrated by reverse transcriptase-polymerase
      chain reaction and partial sequence analysis. A phosphorothioate antisense
      oligonucleotide, complementary to the 5' end of the open reading frame of Xenopus
      CFTR, was used to inhibit functional expression of CFTR in A6 cells. Parallel
      studies utilized the corresponding sense oligonucleotide as a control. CFTR
      protein expression was markedly reduced in cells incubated with the antisense
      oligonucleotide. Incubation of A6 cells with the antisense oligonucleotide led to
      inhibition of forskolin-activated amiloride-insensitive short circuit current
      (Isc). After a 30-min exposure to 10 microM forskolin, 8-pS Cl- channel activity
      was detected in only 1 of 31 (3%) cell-attached patches on cells treated with
      antisense oligonucleotide, compared to 5 of 19 (26%) patches from control cells.
      A shift in the single-channel current-voltage relationship derived from antisense
      treated cells was also consistent with a reduction in Cl- reabsorption. Both
      amiloride-sensitive Isc and Na+ channel Po were significantly increased in
      antisense-treated, forskolin-stimulated A6 cells, when compared with forskolin
      stimulated controls. These data suggest that the regulation of Na+ channels by
      CFTR is not limited to respiratory epithelia and to epithelial cells in culture
      overexpressing CFTR and epithelial Na+ channels.

PMID- 8995303
TI  - Hypoxia induces cyclooxygenase-2 via the NF-kappaB p65 transcription factor in
      human vascular endothelial cells.
AB  - The inducible cyclooxygenase, COX-2, has been associated with vascular
      inflammation and cellular proliferation. We have discovered that hypoxia
      increases expression of the COX-2 gene in human vascular endothelial cells in
      culture independent of other stimuli. Western analysis of human umbilical vein
      endothelial cells (HUVEC) revealed a greater than 4-fold induction of protein by
      hypoxia (1% O2). The steady-state level of COX-2 mRNA was correspondingly
      elevated by both Northern blot and reverse transcriptase-polymerase chain
      reaction analysis. Using electrophoretic mobility shift assays with antibody
      supershifting, we also found that hypoxia causes increased binding of NF-kappaB
      p65 (Rel A) to the one out of the two NF-kappaB consensus elements in the COX-2
      promoter which is closest to the transcription start site of the COX-2 gene.
      Transfection of an immortalized human microvascular endothelial cell line (HMEC
      1) with mutation reporter gene constructs and HUVEC with both mutation and
      deletion reporter gene constructs suggested that transcription of the COX-2 gene
      was enhanced by hypoxia. In transcription factor decoy experiments, hypoxic HUVEC
      were exposed in culture to 20 microM of the same NF-kappaB element found to bind
      NF-kappaB protein. The wild type transcription factor decoy prevented hypoxic
      induction of COX-2, presumably by binding with cytoplasmic p65; however, mutated
      or scrambled oligonucleotides did not prevent the increase in COX-2 protein
      expression by hypoxia. Thus, the intracellular signaling mechanism that leads to
      induction of COX-2 by hypoxia includes binding of p65 to the relatively 3' NF
      kappaB consensus element in the COX-2 upstream promoter region in human vascular
      endothelial cells.

PMID- 8995304
TI  - Modulation of the activity of RNase E in vitro by RNA sequences and secondary
      structures 5' to cleavage sites.
AB  - The endoribonuclease RNase E is believed to initiate the degradation of many
      mRNAs in Escherichia coli, yet the mechanism by which it recognizes cleavage
      sites is poorly understood. We have prepared derivatives of the mRNA encoding
      ribosomal protein S20 which contain a single major RNase E cleavage site at
      residues 300/301 preceded by variable 5' extensions. Three of these RNAs are
      cleaved in vitro with significantly reduced efficiencies relative to the intact
      S20 mRNA by both crude RNase E and pure Rne protein (endonuclease component of
      RNase E). In all three substrates as well as in the full-length mRNA the major
      cleavage site itself remains single-stranded. One such substrate (t84D) contains
      a 5' stem-loop structure characterized by three noncanonical A-G pairs. Removal
      or denaturation of the stem restores efficient cleavage at the major RNase E
      site. The other two contain single-stranded 5'-termini but apparently lack
      cleavage sites near the termini. Our data show that sensitivity to RNase E can be
      influenced by distant structural motifs in the RNA and also suggest a model in
      which the initial recognition and cleavage of a substrate near its 5' end
      facilitates sequential cleavages at more distal sites. The model implies that
      RNase E contains at least a dimer of the Rne subunit and that the products of the
      first cleavage are retained by Rne prior to the second cleavage.

PMID- 8995306
TI  - Combinatorial screening and rational optimization for hybridization to folded
      hepatitis C virus RNA of oligonucleotides with biological antisense activity.
AB  - We describe our initial application of a biochemical strategy, comprising
      combinatorial screening and rational optimization, which directly identifies
      oligonucleotides with maximum affinity (per unit length), specificity, and rates
      of hybridization to structurally preferred sites on folded RNA, to the problem of
      design of antisense oligonucleotides active against the hepatitis C virus (HCV).
      A fully randomized sequence DNA oligonucleotide (10-mer) library was equilibrated
      with each of two folded RNA fragments (200 and 370 nucleotides (nt)), together
      spanning the 5' 440 nt of an HCV transcript (by overlapping 130 nt), which were
      varied over a range of concentrations. The equilibrations were performed in
      solution under conditions determined to preserve RNA structure and to limit all
      RNA-DNA library oligonucleotide interactions to 1:1 stoichiometry. Subsequent
      Escherichia coli RNase H (endoribonuclease H: EC 3.1.26.4) cleavage analysis
      identified two preferred sites of highest affinity heteroduplex hybridization.
      The lengths and sequences of different substitute chemistry oligonucleotides
      complementary to these sites were rationally optimized using an iterative and
      quantitative analysis of binding affinity and specificity. Thus, DNA
      oligonucleotides that hybridized with the same affinity to the preferred sites in
      the folded RNA fragments found by screening as to short (< or = 25 nt) RNA
      complements were identified but were found to vary in length (10-18 nt) from site
      to site. Phosphorothioate (P=S) and 2'-fluoro (2'-F) uniformly substituted
      oligonucleotides also were found, which hybridized optimally to these sites,
      supporting the design of short (10-15-nt) and maximally specific oligonucleotides
      that are more nuclease-resistant (via P=S) and have higher affinity (via 2'-F)
      than DNA. Finally, the affinities of DNA and uniform 2'-F-, P=S-substituted 10-20
      mer oligonucleotide complements for the best hybridization site, from HCV nt 355
      to nt 364-374, closely corresponded to antisense mechanism inhibition activities
      in an in vitro translation assay and in a human cell-based HCV core protein
      expression assay, respectively. These results validate our strategy for the
      selection of hybridization-optimized and biologically active antisense
      oligonucleotides targeting HCV RNA and support the potential for utility in
      further applications.

PMID- 8995305
TI  - Molecular cloning and functional reconstitution of a urate transporter/channel.
AB  - Maintenance of urate homeostasis requires urate efflux from urate-producing cells
      with subsequent renal and gastrointestinal excretion. The molecular basis for
      urate transport, however, has not been identified. A novel full-length cDNA
      encoding a 322-amino acid protein, designated UAT (urate transporter), has been
      cloned from a rat renal cDNA library by antibody screening. UAT mRNA transcripts
      that approximate 1.55 kilobases are present, but differentially expressed in
      various rat tissues. Recombinant UAT protein that was expressed from the cloned
      cDNA in Escherichia coli and purified via immobilized metal affinity
      chromatography has been functionally reconstituted as a highly selective urate
      transporter/channel in planar lipid bilayers. The IgG fraction of the polyclonal
      antibody that was used to select the UAT clone from the cDNA library, but not
      nonimmune IgG, blocked urate channel activity. Based on the wide tissue
      distribution of the mRNA for UAT we propose that UAT provides the molecular basis
      for urate flux across cell membranes, allowing urate that is formed during purine
      metabolism to efflux from cells and serving as an electrogenic transporter that
      plays an important role in renal and gastrointestinal urate excretion.

PMID- 8995307
TI  - Identification of hormonogenic tyrosines in fragment 1218-1591 of bovine
      thyroglobulin by mass spectrometry. Hormonogenic acceptor TYR-12donor TYR-1375.
AB  - A fragment of bovine thyroglobulin encompassing residues 1218-1591 was prepared
      by limited proteolysis with thermolysin and continuous-elution polyacrylamide gel
      electrophoresis in SDS. The reduced and carboxymethylated peptide was digested
      with endoproteinase Asp-N and fractionated by reverse-phase high performance
      liquid chromatography. The fractions were analyzed by electrospray and fast atom
      bombardment mass spectrometry in combination with Edman degradation. The post
      translational modifications of all seven tyrosyl residues of the fragment were
      characterized at an unprecedented level of definition. The analysis revealed the
      formation of: 1) monoiodotyrosine from tyrosine 1234; 2) monoiodotyrosine,
      diiodotyrosine, triiodothyronine (T3), and tetraiodothyronine (thyroxine, T4)
      from tyrosine 1291; and 3) monoiodotyrosine, diiodotyrosine, and dehydroalanine
      from tyrosine 1375. Iodothyronine formation from tyrosine 1291 accounted for 10%
      of total T4 of thyroglobulin (0.30 mol of T4/mol of 660-kDa thyroglobulin), and
      8% of total T3 (0.08 mol of T3/mol of thyroglobulin). This is the first
      documentation of the hormonogenic nature of tyrosine 1291 of bovine
      thyroglobulin, as thyroxine formation at a corresponding site was so far reported
      only in rabbit, guinea pig, and turtle thyroglobulin. This is also the first
      direct identification of tyrosine 1375 of bovine thyroglobulin as a donor
      residue. It is suggested that tyrosyl residues 1291 and 1375 may support together
      the function of an independent hormonogenic domain in the mid-portion of the
      polypeptide chain of thyroglobulin.

PMID- 8995308
TI  - N-methyl-D-aspartate receptors expressed in a nonneuronal cell line mediate
      subunit-specific increases in free intracellular calcium.
AB  - N-methyl-D-aspartate (NMDA) receptors can mediate cell death in neurons and in
      non-neuronal cells that express recombinant NMDA receptors. In neurons, increases
      in intracellular calcium correlate with NMDA receptor-mediated death, supporting
      a key role for loss of cellular calcium homeostasis in excitotoxic cell death. In
      the present study, free intracellular calcium concentrations were examined in
      response to activation of recombinant NMDA receptors expressed in human embryonic
      kidney 293 cells. Intracellular calcium was measured in transfected cell
      populations by cotransfection with the calcium-sensitive, bioluminescent protein
      aequorin and by single cell imaging with the fluorescent calcium indicator fluo
      3. Agonist application to NR1/2A or NR1/2B-transfected cells elicited robust
      rises in intracellular calcium. NR1/2A responses were inhibited by the
      noncompetitive antagonists MK-801 and dextromethorphan and were dependent on
      extracellular calcium but not on intracellular calcium stores. In contrast, no
      detectable intracellular calcium responses were observed in NR1/2C-transfected
      cells. These findings indicate that NMDA receptors in the absence of other neuron
      specific factors can mediate increases in intracellular calcium with subunit
      specificity and extracellular calcium dependence.

PMID- 8995309
TI  - p75, a member of the heat shock protein family, undergoes tyrosine
      phosphorylation in response to oxidative stress.
AB  - The combination of H2O2 and vanadate generates aqueous peroxovanadium (pV)
      species, which are effective cell-permeable oxidants, and potent inhibitors of
      protein-tyrosine phosphatases. As a result, treatment of intact cells with pV
      compounds significantly enhances protein Tyr phosphorylation. Here we demonstrate
      that treatment of intact rat hepatoma Fao cells with pV markedly enhances Tyr
      phosphorylation of a 75-kDa protein, termed pp75. Amino-terminal sequencing of
      pp75 revealed that this protein is a member of the 70-75-kDa heat shock protein
      family, which includes PBP-74, glucose-related protein (GRP)-75, and mortalin.
      Tyr phosphorylation of pp75 is selective, because other proteins that belong to
      the heat shock protein 70 family, such as GRP-72, Bip (GRP-78), and HSC-70 fail
      to undergo Tyr phosphorylation when cells are treated with pV. Our findings
      suggest that heat shock proteins such as pp75 may undergo tyrosine
      phosphorylation when intact cells are subjected to oxidative stress induced by pV
      compounds.

PMID- 8995310
TI  - Identification of a multihormone responsive enhancer far upstream from the human
      tissue-type plasminogen activator gene.
AB  - A 2.4-kilobase (kb) DNA fragment, located 7.1 kb upstream from the human tissue
      type plasminogen activator (t-PA) gene (t-PA2.4), acts as an enhancer which is
      activated by glucocorticoids, progesterone, androgens, and mineralocorticoids.
      Transient expression of t-PA-chloramphenicol acetyltransferase reporter
      constructs in HT1080 human fibrosarcoma cells identified a glucocorticoid
      responsive unit with four functional binding sites for the glucocorticoid
      receptor, located between bp -7,501 and -7,974. The region from bp -7,145 to 
      9,578 (t-PA2.4) was found to confer a cooperative induction by dexamethasone and
      all-trans-retinoic acid (RA) to its homologous and a heterologous promoter,
      irrespective of its orientation. The minimal enhancer, defined by progressive
      deletion analysis, comprised the region from -7.1 to -8.0 kb (t-PA0.9) and
      encompassed the glucocorticoid responsive unit and the previously identified RA
      responsive element located at -7.3 kb (Bulens, F., Ibanez-Tallon, I., Van Acker,
      P., De Vriese, A., Nelles, L., Belayew, A., and Collen, D. (1995) J. Biol. Chem.
      270, 7167-7175). The amplitude of the synergistic response to dexamethasone and
      RA increased by reducing the distance between the enhancer and the proximal t-PA
      promoter. The synergistic interaction was also observed between the aldosterone
      and the RA receptors. It is postulated that the t-PA0.9 enhancer might play a
      role in the hormonal regulation of the expression of human t-PA in vivo.

PMID- 8995311
TI  - Two naturally occurring alpha2,6-sialyltransferase forms with a single amino acid
      change in the catalytic domain differ in their catalytic activity and proteolytic
      processing.
AB  - The alpha2,6-sialyltransferase (ST) is a Golgi glycosyltransferase that adds
      sialic acid residues to glycoprotein N-linked oligosaccharides. Here we show that
      two forms of alpha2,6-sialyltransferase are expressed by the liver and are
      encoded by two different RNAs that differ by a single nucleotide. The ST tyr
      possesses a Tyr at amino acid 123, whereas the ST cys possesses a Cys at this
      position. The ST tyr is more catalytically active than the ST cys; however, both
      are functional when introduced into tissue culture cells. The proteolytic
      processing and turnover of the ST tyr and ST cys proteins differ dramatically.
      The ST cys is retained intact in COS-1 cells, whereas the ST tyr is rapidly
      cleaved and secreted. Analysis of the N-linked oligosaccharides of these proteins
      demonstrates that both proteins enter the late Golgi. However, differences in ST
      tyr and ST cys proteolytic processing may be related to differences in their
      localization, because ST tyr but not ST cys is expressed at low levels on the
      cell surface. The possibility that the ST tyr is cleaved in a post-Golgi
      compartment is supported by the observation that a 20 degrees C temperature
      block, which stops protein transport in the trans Golgi network, blocks both
      cleavage and secretion of the ST tyr.

PMID- 8995312
TI  - Amino acid substitutions that convert the protein substrate specificity of
      farnesyltransferase to that of geranylgeranyltransferase type I.
AB  - Protein farnesyltransferase (FTase), a heterodimer enzyme consisting of alpha and
      beta subunits, catalyzes the addition of farnesyl groups to the C termini of
      proteins such as Ras. In this paper, we report that the protein substrate
      specificity of yeast FTase can be switched to that of a closely related enzyme,
      geranylgeranyltransferase type I (GGTase I) by a single amino acid change at one
      of the three residues: Ser-159, Tyr-362, or Tyr-366 of its beta-subunit, Dpr1.
      All three Dpr1 mutants can function as either FTase or GGTase I beta subunit in
      vivo, although some differences in efficiency were observed. These results point
      to the importance of two distinct regions (one at 159 and the other at 362 and
      366) of Dpr1 for the recognition of the protein substrate. Analysis of the
      protein, after site directed mutagenesis was used to change Ser-159 to all
      possible amino acids, showed that either asparagine or aspartic acid at this
      position allowed FTase beta to function as GGTase I beta. A similar site-directed
      mutagenesis study on Tyr-362 showed that leucine, methionine, or isoleucine at
      this position also resulted in the ability of mutant FTase beta to function as
      GGTase I beta. Interestingly, in both position 159 and 362 substitutions, amino
      acids that could change the protein substrate specificity had similar van der
      Waals volumes. Biochemical characterization of the S159N and Y362L mutant
      proteins showed that their kcat/Km values for GGTase I substrate are increased
      about 20-fold compared with that of the wild type protein. These results
      demonstrate that the conversion of the protein substrate specificity of FTase to
      that of GGTase I can be accomplished by introducing a distinct size amino acid at
      either of the two residues, 159 and 362.

PMID- 8995313
TI  - Mechanism of E1A-induced transforming growth factor-beta (TGF-beta) resistance in
      mouse keratinocytes involves repression of TGF-beta type II receptor
      transcription.
AB  - Cellular transformation driven by the E1A oncogene is associated with the
      development of cellular resistance to the growth inhibitory effects of
      transforming growth factor-beta (TGF-beta). We demonstrate that development of
      resistance occurs simultaneously with decreased expression of TGF-beta type II
      receptor (TGF-beta RII) mRNA and protein. To determine whether changes in
      transcriptional regulation are responsible for the decreased receptor expression
      in E1A-transformed cells, a series of mobility shift assays was performed
      utilizing nuclear extracts from E1A-transformed and untransformed murine
      keratinocytes using radiolabeled positive regulatory elements (PRE1 and PRE2) of
      the TGF-beta RII promoter. The results from these assays suggest that E1A
      transformed cells express markedly lower levels of nuclear proteins that bind
      specifically to PRE1 and PRE2. Transfection of both E1A-transformed and
      untransformed cell lines with a series of mutant promoter constructs confirmed
      that both PREs contribute significantly to basal expression of TGF-beta RII and
      that inactivation of either element leads to markedly reduced promoter activity.
      We conclude that development of TGF-beta resistance in E1A-transformed cells is
      achieved in part through transcriptional down-regulation of the TGF-beta RII gene
      and that this down-regulation is the result of decreased expression of
      unidentified transcription factor complexes that interact with PRE1 and PRE2.

PMID- 8995314
TI  - Transcription termination by vaccinia RNA polymerase entails recognition of
      specific phosphates in the nascent RNA.
AB  - Vaccinia virus RNA polymerase terminates transcription downstream of a UUUUUNU
      signal in the nascent RNA. Transduction of the RNA signal to the elongating
      polymerase requires a termination factor (vaccinia termination factor/capping
      enzyme) and is coupled to the hydrolysis of ATP. It was shown previously that
      incorporation of 5-bromouracil or 5-iodouracil within the UUUUUNU element
      abolishes termination by preventing factor-dependent release of the nascent chain
      from the polymerase elongation complex. Here, we report that termination is
      prevented by phosphorothioate substitution at UMP residues in the nascent RNA. In
      contrast, phosphorothioate substitution at AMP, CMP, and GMP nucleotides does not
      inhibit termination. Thus, the action of a eukaryotic termination factor entails
      recognition of the nucleotide bases and the phosphate groups of the target
      sequence in nascent RNA.

PMID- 8995326
TI  - Ibogaine and cocaine abuse: pharmacological interactions at dopamine and
      serotonin receptors.
AB  - Ibogaine is an indole alkaloid that has been of interest in recent years due to
      its putative efficacy in the treatment of drug dependence. For the most part,
      animal data have shown attenuation of some of the effects of stimulant drugs, for
      example, motor stimulation and self-administration. The mechanism of this
      inhibition of drug-induced behavior seems to suggest the action of the dopamine,
      serotonin, NMDA, kappa, and/or sigma receptor sites, as indicated by the affinity
      of ibogaine to receptor selective ligands in binding competition studies.
      However, affinity for receptors does not in itself indicate their involvement. In
      vitro perfusion studies have proven a useful model to study the effect of
      ibogaine on neurotransmitter systems and the functional effects of such
      interactions. This review summarizes these data and the support of multiple
      effects of ibogaine, and the potential importance of its action on serotonergic
      modulation of dopamine release.

PMID- 8995327
TI  - Changes in the sensitivity of frontal cortical neurones to acetylcholine after
      unilateral lesion of the nucleus basalis with alpha-amino-3-OH-4-isoxozole
      propionic acid (AMPA): effects of basal forebrain transplants into neocortex.
AB  - Unilateral S-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
      lesions of the nucleus basalis magnocellularis (nbm), which produced persistent
      and extensive ChAT-positive cell loss within the nbm and depletion of cortical
      cholinergic markers in the frontal cortex, increased both the number and
      sensitivity of individual frontal cortical neurones responding to iontophoretic
      administration of ACh. The lesion also increased the sensitivity of individual
      neurones to carbachol but the increase in the number of neurones responding to
      carbachol was transient and had returned to normal 4 weeks after lesion. The
      sensitivity of individual neurones to glutamate was unchanged by the lesion. The
      percentage of cortical neurones responding to ACh, but not the sensitivity of
      individual neurones was restored to the prelesion level, 6-8 weeks after
      cholinergic transplants to the lesioned frontal cortex; cholinergic transplants
      to the more distant parietal cortex were only effective after 6 months whereas
      noncholinergic transplants were ineffective at both time intervals. Cholinergic
      transplants placed in the frontal cortex 6-8 weeks or 6 months before nbm lesion
      offered some protection from the effects of the lesion, particularly at 6 months
      but were ineffective when placed into the parietal cortex. Lesion of the nbm also
      reduced basal firing rate of spontaneously active neurones and this was not
      restored by any of the transplants. The results are discussed in the light of
      quantitative measurements of acetylcholinesterase-positive fibre outgrowth from
      the transplant into the recording area, which are described in the preceding
      manuscript [20].

PMID- 8995328
TI  - The presence of the complement cascade does not lead to neuronal cell death in
      primary hippocampal cultures.
AB  - To investigate the consequences of complement activation on neuronal viability,
      the effects of serum treatment on neuron-rich and mixed neuronal/glial cultures
      were evaluated. The neurotoxicity observed following treatment with either human
      or rat serum was variable and did not appear to be mediated through a complement
      mediated mechanism. Serum lots lacking CH50 activity induced neurotoxicity, and
      heat treatment of toxic lots of either human or rat sera did not abolish
      toxicity. In cases where serum treatment did not induce cell death, treatment
      with PIPLC to remove endogenous membrane-bound complement inhibitors prior to
      serum exposure, did not result in cell death.

PMID- 8995329
TI  - Effect of chemical stimulation of the dorsomedial hypothalamic nucleus on blood
      plasma glucose, triglycerides and free fatty acids in rats.
AB  - The effects of chemical stimulation of the dorsomedial hypothalamic nucleus (DMH)
      on blood plasma concentration of glucose, triglycerides, insulin, and free fatty
      acids (FFA) were investigated in anesthetized adult Wistar rats. Microinjection
      of 12.5 nmol of norepinephrine into the DMH increased blood plasma concentration
      of glucose and FFA, decreased triglycerides, and did not change plasma insulin
      within 5 min; after 20 min, blood glucose and FFA reached control values.
      Microinjection of epinephrine (12.5 nmol) into the DMH also increased blood
      plasma glucose concentration and decreased triglycerides after 5 min. These
      effects are probably mediated by beta-adrenergic mechanisms, because they were
      prevented by beta-adrenergic antagonist propranolol, but not by alpha-adrenergic
      antagonist prazosin. Microinjection into the DMH of glutamate, dopamine, or
      acetylcholine failed to cause any change in those metabolic parameters,
      corroborating the hypothesis that the DMH is part of a beta-adrenergic pathway
      involved in short-term modulation of the availability of glucose and FFA.

PMID- 8995330
TI  - Cholinergic mechanisms responsible for blood pressure regulation on
      sympathoexcitatory neurons in the rostral ventrolateral medulla of the rat.
AB  - We examined whether reticulospinal sympathoexcitatory neurons in the rostral
      ventrolateral medulla (RVLM) have muscarinic receptors and ACh inputs, and
      whether these cholinergic mechanisms on RVLM neurons are involved in the pressor
      response induced by peripheral administration of physostigmine.
      Microiontophoretic application of ACh and carbachol enhanced the firing rate of
      RVLM sympathoexcitatory neurons and the enhancement of RVLM neurons by these
      cholinoceptor agonists was abolished by the nonselective muscarinic receptor
      antagonist scopolamine and/or by the M2 muscarinic receptor antagonist
      methoctramine. Physostigmine and the ACh releaser 3,4-diaminopyridine also
      enhanced the firing rate of RVLM neurons. Intravenous administration of
      physostigmine enhanced RVLM sympathoexcitatory neuronal activity and the
      physostigmine-induced response was reversed by iontophoretic application of
      scopolamine onto the neurons. These results are consistent with the hypothesis
      that M2 muscarinic receptors responsible for blood pressure regulation are
      present on RVLM sympathoexcitatory neurons and these receptors receive ACh
      inputs. Physostigmine injected systemically may exert a portion of its
      hypertensive effect through a direct enhancement of cholinergic mechanisms on
      RVLM sympathoexcitatory neurons.

PMID- 8995331
TI  - Receptor-mediated effects of clonidine on need-induced 3% NaCl and water intake.
AB  - Clonidine combined with adrenergic antagonists were injected in the medial septal
      area in order to characterize the type of receptors involved with its inhibitory
      effect on 3% NaCl and water intake of sodium-depleted (furosemide + 24 h of
      removal of ambient sodium) and 30-h water-deprived rats, respectively. The
      inhibitory effect of clonidine (20 nmol) on need-induced water intake was reduced
      50% by an 80-nmol dose of either idazoxan, yohimbine or prazosin. The inhibitory
      effect of clonidine (30 nmol) on need-induced 3% NaCl intake was completely
      antagonized by idazoxan (80, 160 nmol), not altered by yohimbine (40-160 nmol),
      and partially potentiated (40 nmol) or inhibited (160 nmol) by prazosin.
      Propranolol did not alter the effects of clonidine on either water (80 nmol) or
      3% NaCl (40-160 nmol) intake. The results suggest that the inhibitory effects of
      clonidine on 3% NaCl and water intake are mediated by different types of alpha2
      adrenergic receptors.

PMID- 8995333
TI  - Neurohypophyseal vasopressin in the Syrian hamster: response to short
      photoperiod, pinealectomy, melatonin treatment, or osmotic stimulation.
AB  - In the present study, the effect of photoperiod on vasopressin content in the
      pituitary neurointermediate lobe (NIL), as well as the ability of pinealectomy to
      prevent and melatonin to mimic the short photoperiod-induced changes in NIL
      vasopressin were studied in male Syrian hamsters. The ability of melatonin to
      modify the hyperosmotically stimulated vasopressin release was also determined.
      Exposure to short photoperiod (SD) for 4 or 10 weeks increased vasopressin
      content in the hamster NIL. In long photoperiod (LD)-exposed hamsters,
      pinealectomy induced a decrease in NIL vasopressin content, whereas no effect of
      melatonin injections on vasopressin storage in the NIL was detected. In SD
      exposed animals, pineal removal failed to alter vasopressin content in the NIL.
      Hypertonic saline administration led to the expected decrease in vasopressin
      content in the NIL both in vehicle- and melatonin-treated animals. The
      hyperosmotically stimulated release of vasopressin was not modified by previous
      treatment with melatonin. The data from the present study show that, in male
      Syrian hamsters, exposure of animals to SD increases the vasopressin content in
      the posterior pituitary, but these changes appear not to be mediated by SD
      induced changes in melatonin secretion. Furthermore, the exposure of animals to
      SD prevents the pinealectomy-induced changes in NIL vasopressin content.
      Melatonin does not modify the hyperosmotically stimulated vasopressin release in
      the male Syrian hamster.

PMID- 8995332
TI  - Comparison of neurotensin responses to MDL 100,907, a selective 5HT2A antagonist,
      with clozapine and haloperidol.
AB  - The unique pharmacological profile of atypical antipsychotics, such as clozapine,
      suggests that action on non-dopaminergic transmitter systems might contribute to
      the unique therapeutic benefits of these drugs. In order to test this
      possibility, the response of neurotensin systems to drugs with antipsychotic
      potential was examined because of this peptide's putative association with
      psychiatric disorders. The effects of treatments by haloperidol, clozapine, and
      MDL 100,907 (a selective 5HT2A antagonist thought to have antipsychotic activity)
      on NT pathways were determined in various extrapyramidal and limbic regions and
      compared. The response of neurotensin systems was determined by measuring
      neurotensin-like immunoreactivity after 1, 2, 4, and 5 drug administrations. It
      was observed that tissue content of this peptide in caudate and nucleus accumbens
      regions tended to be elevated after 1 or 2 drug administrations, but had either
      returned or was returning to control levels after 4 or 5 drug administrations. In
      general, the extrapyramidal and limbic neurotensin levels responded in a similar
      manner to clozapine and the 5HT2A antagonist, but differently for haloperidol in
      most regions examined. An important exception was in the nucleus accumbens, where
      all three drugs had similar effects on neurotensin tissue levels. These results
      suggest that 5HT2A receptors exert basal control over some extrapyramidal and
      limbic neurotensin systems and this interaction might contribute to the
      antipsychotic effects of these drugs.

PMID- 8995335
TI  - Autoradiographic characterization of rat spinal neuropeptide FF receptors by
      using [125I][D.Tyr1, (NMe)Phe3]NPFF.
AB  - The binding properties of neuropeptide FF (NPFF) receptors were investigated in
      different laminae of the rat spinal cord by using quantitative autoradiography
      and [125I][D.Tyr1, (NMe)Phe3]NPFF as radioligand. In the superficial layers, the
      specific binding of [125I][D.Tyr1, (NMe)Phe3]NPFF was time-dependent, reversible,
      and saturable (KD = 0.1 nM). Preincubation of spinal sections increased the
      maximal number of [125I][D.Tyr1, (NMe)Phe3]NPFF binding sites. Bestatin, an
      inhibitor of aminopeptidases, increased significantly the apparent affinity of
      NPFF. Optimal binding of [125I][D.Tyr1, (NMe)Phe3]NPFF was observed in the
      presence of 120 mM NaCl in all laminae of the spinal cord. No significant
      differences were noted in the salt dependence in laminae I-II, IV-V, and X, and
      the pharmacological profile of [125I][D.Tyr1, (NMe)Phe3]NPFF binding was similar
      in each laminae. These results do not support the existence of NPFF receptors
      subtypes differentially localized in different area of the spinal cord. Our data
      reveal the effects of tissue treatments on binding characteristics of NPFF
      receptors and indicate that [125I][D.Tyr1, (NMe)Phe3]NPFF is a useful radioactive
      probe for the characterization of NPFF receptors in discrete brain areas.

PMID- 8995334
TI  - Estradiol masculinizes the number of accessory olfactory bulb mitral cells in the
      rat.
AB  - Orchidectomized males injected with a single dose of estradiol benzoate on the
      day of birth (D1) showed mitral cell numbers in the accessory olfactory bulb
      similar to those of control males. However, orchidectomized males that received
      no additional estradiol benzoate treatment and those orchidectomized and given a
      single dose of dihydrotestosterone on D1 showed decreases in the number of
      accessory olfactory bulb mitral cells compared with control males. These results
      support the notion that the presence of estradiol immediately after birth induces
      the masculinization of mitral cells number in the accessory olfactory bulb.

PMID- 8995336
TI  - Antinociceptive interaction between alprazolam and opioids.
AB  - Alprazolam is a triazolobenzodiazepine, with a potent anxiolytic action and a
      short half-life. Alprazolam analgesia was measured, using the radiant heat
      tailflick assay in mice, which was administered alone or in combination with
      opioids. Intrathecally administered alprazolam produced a dose-response increase
      in the tailflick latency with an ED50 of 34 microg (19.4-72.5, 95% CL). There
      were almost no effects after intracerebroventricular injections. Naloxone almost
      completely abolished the analgesia response mediated by alprazolam. This
      sensitivity to naloxone indicates that at least some of the analgesic effects of
      alprazolam are mediated by an opioid mechanism of action. When administered
      together with various antagonists of opioid receptor subtypes, we found that the
      mu antagonists, but not the delta and kappa1 subtypes inhibited alprazolam
      analgesia significantly. No effect was found when alprazolam was coadministrated
      with kappa3 opioid agonists. In addition, we found a supra-additivity
      (synergistic) increase in analgesia when alprazolam was given with morphine.
      Competition binding assays show the highest affinity of alprazolam to the mu1
      subtype. In summary, we conclude that alprazolam mediates its analgesic effect,
      most probably via an mu opiate mechanism of action.

PMID- 8995337
TI  - Local venous thrombosis after cardiac catheterization.
AB  - Pulmonary embolism is a rare but life-threatening complication of cardiac
      catheterization. Underlying deep venous thrombosis (DVT) is often not detectable
      clinically. To determine the true incidence of DVT the authors prospectively
      studied 450 consecutive patients (29% women, 71% men, mean age: fifty-eight
      years) undergoing a diagnostic cardiac catheterization. Patients were examined
      clinically and by duplex sonography with a high-resolution (5 or 7.5 MHz)
      transducer before and twenty-four hours after catheterization before
      mobilization. Duplex sonography excluded complete proximal DVT in all patients.
      Only partial occluding thrombi (pDVT) were detected in 11 (2.4%) patients. The
      thrombi were always localized at the puncture site. In 2 patients a difference
      was found in the circumferences of the legs, but no other clinical signs of DVT
      were seen. With use of continuous wave (cw) Doppler sonography, only 3 of these
      11 patients (27%) showed a spontaneous (s) sound. Phlebography was performed in
      4/11 patients (36%). In 2 patients the diagnosis was confirmed; in 1 patient
      extravenous compression was assumed, and the other demonstrated a normal
      appearing phlebography at the time of investigation. Logistic regression analysis
      yielded a 3.5 times higher risk for developing a pDVT if a venous puncture was
      performed in addition to arterial puncture. Furthermore a 9.8 times higher risk
      was found if more than one venous puncture was necessary. During the follow-up no
      patient developed clinical signs of pulmonary embolism. The results of this study
      demonstrate that DVT is a rare complication of cardiac catheterization (0/450
      patients), but pDVT occurred in 2.4%. Risk factors for pDVT are the venous
      puncture itself and multiple puncture attempts. Clinical relevance of pDVT
      remains to be determined.

PMID- 8995339
TI  - Chronic venous insufficiency--a well-known disorder with many question marks.
AB  - Chronic venous insufficiency (CVI) is a common disorder found in many parts of
      the world. The pathophysiology of this condition is only partly elucidated, and
      even the development of varicose veins remains unexplained. Microcirculation is
      greatly affected by CVI, which occasionally induces skin changes and ulcers.
      Although varicose veins are a common symptom of CVI, they are absent in many
      patients. Thus, clinical examination is often insufficient for the diagnosis of
      CVI. Furthermore, the treatment of a common disorder such as CVI is frequently
      inadequate. The author discusses the overfrequent use of varicose vein surgery,
      where compression treatment would seem more appropriate and effective, and the
      current status of compression in the treatment of deep vein incompetence. He
      recommends that the various manifestations of CVI should be more thoroughly
      classified. He also examines how sclerotherapy is used to various extents in
      different countries. Finally he discusses the use of various drugs in the
      treatment of CVI. It is clear that the pathophysiology and the treatment of CVI
      must be further examined, in particular to determine whether prevention is
      possible.

PMID- 8995338
TI  - Comparative ultrasonographic and angiographic study of carotid arterial lesions
      in Takayasu's arteritis.
AB  - The purpose of this study was to compare the usefulness of ultrasonography to
      that of angiography for studying arterial lesions in Takayasu's arteritis.
      Ultrasonographic and angiographic findings from 44 carotid arteries of 22
      patients with Takayasu's arteritis (2 men and 20 women; mean age, 41.2 years)
      were compared. Angiography was used to classify the patency of the carotid
      arteries into three groups: nonstenotic, stenotic, and occlusive. Ultrasonography
      was also used to classify the same arteries into four groups: nonstenotic, mildly
      stenotic, moderately stenotic, and occlusive. Thickness of the wall (intima-media
      complex) of the carotid artery was measured with high-frequency transducers.
      Angiography showed 23 carotid arteries to be nonstenotic; 12, stenotic; and 9,
      occlusive; whereas ultrasonography showed 16 to be nonstenotic; 18, mildly
      stenotic; 7, moderately stenotic; and 3, occlusive. Results of the two diagnostic
      modalities correlated closely (P < 0.0001). Ultrasonography, aided by color flow
      imaging, detected six instances of a marginal but definite blood flow that
      angiography had failed to reveal. Arterial wall thickness correlated closely with
      the severity of ultrasonographic stenosis (P < 0.005). This thickness was 1.3 +/-
      0.4 mm in the nonstenotic group, 1.6 +/- 0.5 mm in the mildly stenotic group, 2.2
      +/- 0.8 mm in the moderately stenotic group, and 1.9 +/- 0.2 mm in the occlusive
      group. Even the walls of the nonstenotic arteries were significantly thicker than
      those of the normal carotid arteries (0.7 +/- 0.1 mm, P < 0.01). Ultrasonography
      appeared to be more useful than angiography in estimating stenotic severity of
      the carotid artery in Takayasu's arteritis. Characteristic ultrasonic findings
      included luminal stenosis or occlusion on two-dimensional ultrasonograms,
      decrease in or lack of flow shown by color Doppler flow imaging, and concentric
      thickening of the carotid arterial walls. Ultrasonographic mural thickness was
      the most sensitive indicator of early, latent inflammation.

PMID- 8995340
TI  - Microvascular changes in venous disease: an update.
AB  - In an overview the microvascular involvement in chronic venous insufficiency
      (CVI) is described. Microangiopathy in the lower leg areas is characterized by
      the presence of typical enlarged and ramified blood capillaries, reduced
      capillary number, microvascular thrombosis and obliterations, and/or increased
      permeability of microlymphatics. Transcutaneous oxygen tension (tcPO2) is
      decreased and directly correlated to the number of perfused capillaries, whereas
      laser Doppler flux is enhanced. This apparent paradox may be explained by
      hyperperfusion in the deeper skin layers (mainly shunt vessels) and hypoperfusion
      in the superficial nutritive vessels. Microvascular changes are of patchy
      distribution. Trophic changes up to overt venous ulceration are mainly caused by
      microvascular ischemia and edema formation due to increased capillary
      permeability and deficient lymphatic drainage.

PMID- 8995341
TI  - Microvascular reactivity after ischemia/reperfusion in the hamster cheek pouch:
      beneficial effects of different oral doses of S-5682 (Daflon 500 mg).
AB  - Daflon 500 mg (S-5682) is a purified, micronized flavonoid fraction containing
      90% diosmin and 10% hesperidin that is currently used to treat chronic venous
      insufficiency and hemorrhoidal disease. Thus, it seemed of interest to evaluate
      the effects of S-5682 on ischemia/reperfusion, ie, the changes in mean internal
      diameter and blood flow of arterioles and venules and the functional capillary
      density (FCD) during reperfusion after ninety minutes of total ischemia in the
      hamster cheek pouch microvasculature. Different doses of S-5682 (5, 20, 80, and
      160 mg/kg body weight/day), suspended in 10% lactose solution or vehicle (10%
      lactose) were administered orally to male hamsters for ten days twice a day. The
      cheek pouch preparation was placed under an intravital microscope coupled to a
      closed-circuit TV system. A ninety-minute local ischemia was obtained by a cuff
      mounted around the neck of the everted pouch where it left the mouth of the
      hamster. Mean arteriolar and venular internal diameters were determined by means
      of an image-shearing device, IPM model 907; red blood cell (RBC) velocity was
      measured by the dual-slit photometric technique; microvessel volume flow was
      calculated from diameters and RBC velocities; and FCD was defined as the number
      of red-cell-perfused capillaries per observation field. During reperfusion,
      placebo-treated animals showed significant vasodilatation concomitant with a
      decrease in blood flow and FCD compared with preischemic values and an impairment
      of the myogenic response. In S-5682-treated animals, there was a significant dose
      dependent improvement in all these parameters including the myogenic tonus. These
      results clearly demonstrated that oral administration of different doses of S
      5682 for ten days improved the microvascular reactivity and FCD after
      ischemia/reperfusion in a dose-dependent fashion in the hamster cheek pouch
      microvasculature.

PMID- 8995342
TI  - Antioxidant effect of flavonoids.
AB  - Our body generates hydroxyl radicals under a number of conditions. This radical
      is very unstable and, therefore, very reactive. After attack of radicals on
      membranes and lipoproteins, lipid peroxidation starts, and may lead to the
      development of vascular lesions. The human body has developed antioxidant
      defenses to protect against free radicals such as superoxide dismutases,
      glutathione peroxidases, plasma iron binding proteins, or alpha tocopherol.
      Oxidized LDL are believed to play a key role in vascular damage and can modulate
      several endothelial properties including NO production and expression of adhesion
      molecules. Antioxidants, such as flavonoids, inhibit "in vitro" oxidation of LDL
      and their cytotoxicity; in humans consumption of flavonoids appears to be related
      to a reduction of the risk of cardiovascular diseases. The biochemical mechanisms
      responsible for this effect remain to be addressed.

PMID- 8995343
TI  - Venous elasticity after treatment with Daflon 500 mg.
AB  - It has been demonstrated that patients predisposed to the development of varicose
      veins have an abnormal venous tone, and may have symptoms in the absence of
      obvious varicosities. It has been suggested that venotonic drugs relieve the
      symptoms of chronic venous insufficiency by decreasing capillary leakage and
      improving venous tone. The aim of this study was to determine the effect of
      Daflon 500 mg in patients with abnormal venous elasticity without varicose veins.
      Twenty-five healthy female volunteers aged 18-35 were included in the study. They
      presented with symptomatic varicose veins in one leg and an abnormal elastic
      modulus without varicosities in the opposite leg. Treatment group: 12 patients
      received 2 tablets of Daflon 500 mg (1000 mg/day); control group: 13 patients
      received no treatment. The elastic modulus K was determined using the air
      plethysmograph. Simultaneous measurements of calf volume changes were made in
      response to different venous pressures produced by a thigh pneumatic cuff. In the
      control group K (mean +/- sd) was 10.8 x 10(3) +/- 4.1 x 10(3) N/m2 at the
      beginning and 10.2 x 10(3) +/- 3.1 x 10(3) N/m2 at the end of the study (P >
      0.1). In the treatment group the initial K was 10.2 x 10(3) +/- 3.9 x 10(3) N/m2
      and 14.2 x 10(3) +/- 5.1 x 10(3) N/m2 at the end (P < 0.02). The results of the
      Wilcoxon rank sum test indicated that 4 weeks' therapy with Daflon 500 mg is
      effective in improving venous tone in patients with symptoms but without varicose
      veins.

PMID- 8995344
TI  - Measuring health-related quality of life in venous disease: practical and
      scientific considerations.
AB  - An important and often neglected aspect in the evaluation of patient outcomes in
      venous disease is quality of life. This paper addresses the why, what, and how of
      measuring health-related quality of life (HRQL) in venous disease by providing an
      overview of practical and scientific considerations in developing and using
      measures of HRQL in general. It begins with a brief overview of developments in
      the field of measuring HRQL and the definition of HRQL. This is followed by a
      consideration of issues relevant to the assessment of HRQL including generic and
      disease-specific measures, multiple components of HRQL, different methods of
      measurement, measuring change, and cultural appropriateness of HRQL measures. In
      the next section, criteria for evaluating the scientific credibility and
      practical utility of HRQL measures are outlined, followed by a description of
      some widely used generic and disease-specific measures of HRQL, including
      measures of HRQL in chronic venous disorders of the leg (CVDL).

PMID- 8995345
TI  - The VEINES study (VEnous Insufficiency Epidemiologic and Economic Study): an
      international cohort study on chronic venous disorders of the leg. VEINES Group.
AB  - The aim of the VEINES study is to address some gaps in knowledge regarding the
      multidimensional repercussions of venous disorders and the measurement of
      outcomes. Its objectives are to describe and compare defined clinical
      presentations of venous-related leg disorders with regard to natural history,
      clinical outcome, functional capacity, quality of life, and economic impact. A
      secondary objective is to develop or identify and test standardized instruments
      for the evaluation of therapeutic effectiveness. This paper presents an overview
      of the design of the study and of the options chosen for the recruitment process
      and the outcome measures.

PMID- 8995346
TI  - Socioeconomic impact of chronic venous insufficiency and leg ulcers.
AB  - Chronic venous insufficiency affects approximately 5% and chronic leg ulcer
      approximately 1% of the adult population of developed countries. Not only do
      recent quality of life studies highlight major disability and social impairment
      but, since this is a condition characterized by chronicity and relapse, it gives
      rise to massive health care expenditure amounting in the UK to around Pounds 400
      million per annum. Venous disease consumes 1-2% of the health care budgets of
      European countries. Imprecise disease classifications and codings impede the
      acquisition of accurate data but there is a compelling need for better quality
      socioeconomic data concerning this long-neglected health care problem.

PMID- 8995347
TI  - Pathophysiology of venous leg ulceration--an update.
AB  - The microcirculatory component of the pathophysiology of venous ulceration is now
      attracting considerable research interests, but is still far from fully
      elucidated. Currently, the central role is filled by the inappropriately
      activated white cell and its interaction with the endothelium. Interstitial
      oedema, pericapillary fibrin cuff and capillary microthromboses could all fit in
      with this hypothesis. However, there are other demonstrated changes, for instance
      in lymphatic drainage, intrinsic fibrinolysis and hemorheological changes which
      also need to be taken into account. The interaction between the microcirculatory
      changes is an obvious target for the systemic pharmacotherapy of venous
      ulceration.

PMID- 8995348
TI  - Efficacy of Daflon 500 mg in venous leg ulcer healing: a double-blind,
      randomized, controlled versus placebo trial in 107 patients.
AB  - The objective of this study was to evaluate the efficacy of Daflon 500 mg (Dios)*
      in venous ulcers. A multicenter, double-blind, randomized, controlled versus
      placebo (Plac) trial was conducted, with stratification according to the size of
      ulcer (< or = 10 cm and > 10 cm). The protocol called for a two-month treatment
      with Dios (one tablet = 450 mg micronized purified Diosmin) or a placebo, two
      tablets/day, in addition to compression therapy. Evaluations were performed every
      fifteen days, from D0 to D60. The primary endpoint, in accordance with Alexander
      House group requirements were: percentage of patients with complete ulcer
      healing, ie, comparison between Dios and Plac group at D60, and comparison of
      survival curves in each group between D0 and D60 (log rank test). Secondary
      endpoints included ulcer surface area assessed by computerized planimetric
      measurements, qualitative evaluation of ulcers, and symptoms. The patients were
      105 men and women ranging in age from eighteen to eighty-five years, with
      standard compression stocking, who were undergoing standardized local care of
      ulcer and had no significant arterial disease (ankle/arm systolic pressure index
      > 0.8). Fifty-three patients received Dios, and 52 received Plac. The 2 groups
      were well matched for age (m +/- 1 SD = seventy-one +/- eleven years), gender,
      ulcer size, and associated disorders. Among patients with ulcer size < or = 10 cm
      (Dios = 44, Plac = 47) a significantly larger number of patients had a complete
      ulcer healing at two months in the Dios group (n = 14) in comparison with the
      Plac group (n = 6) (32% vs 13%, P = 0.028) with a significantly shorter time
      duration of healing (P = 0.037). No difference was shown for the secondary
      criteria, except for sensation of heavy legs (P = 0.039) and a less atonic aspect
      of ulcer (P = 0.030) in favor of Dios. Among the 14 patients with ulcer size > 10
      cm (Dios = 9, Plac = 5), subjected to a descriptive analysis only, no ulcer
      healed. This study showed that a two-month course of Daflon 500 mg at a daily
      dose of two tablets, in addition to conventional treatment, is of benefit in
      patients with venous ulcer < or = 10 cm by accelerating complete healing.

PMID- 8995349
TI  - Therapy approaches for lymphedema.
AB  - Lymphedema, regardless of etiology, is essentially incurable but different
      therapy approaches exist which serve to contain swelling. The objectives of
      treatment are to reduce swelling, restore shape, and prevent inflammatory
      episodes, eg, recurrent cellulitis. There are essentially three main approaches
      to lymphedema treatment: physical therapy, drug therapy, and surgery. Any edema
      arises from an imbalance between capillary filtration and lymph drainage. The
      principle of physical therapy is to a) reduce excessive capillary filtration and
      b) improve drainage of interstitial fluid and macromolecules from congested
      regions to normally draining lymph node sites. This is achieved through a
      combination of compression, exercise, and if possible, massage. Control of
      recurrent inflammatory episodes can only be achieved through diabetic type skin
      care, a reduction in swelling, and if necessary, prophylactic antibiotics. Drug
      therapy comprises diuretics or the coumarin/flavonoid group of drugs. The use of
      diuretics for pure lymphedema is physiologically unsound but may be of use in
      edema of mixed origin and in palliative (cancer) circumstances.
      Coumarin/flavonoids have been shown to reduce swelling in all types of
      lymphedema. Surgery is indicated at an early stage for facial swelling, where
      vision is compromised, or genital lymphedema, where genitourinary function is
      affected. Otherwise, reducing operations should only be performed when
      alternative therapy has failed. Microsurgery for certain forms of lymphedema
      continues to be evaluated.

PMID- 8995350
TI  - Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to
      conventional therapy of breast cancer).
AB  - To assess the activity of a purified, micronized, flavonoidic fraction (Dios;
      Daflon 500 mg*) on upper limb lymphedema occurring after breast cancer therapy, a
      monocenter, randomized, double-blind, parallel group vs placebo (Plac) trial was
      carried out. One hundred and four women with lymphedema were included; 94
      completed the study (46 Dios, 48 Plac). A subset of 24 patients with more severe
      lymphedema (10 Dios, 14 Plac) was subjected to a separate analysis. Treatment
      consisting of Dios or Plac was given two tablets daily over a six-month period. A
      radionuclide lymphoscintigraphy using technetium-99m was performed at inclusion
      and at the end of the treatment. The upper limb volume was measured every two
      months. In the overall population the evolution of parameters was not different
      between Dios and Plac. In the 24 patients with a more severe lymphedema, the
      lymphoscintigraphic parameters (m +/- sd) were as follows: lymphatic migration
      speed was significantly improved by Dios in comparison with Plac (delta Speed
      cm/minute: 0.84 +/- 0.6 vs 0.14 +/- 0.26, P = 0.005). The half-life of the
      colloidal compound was significantly improved over time in the Dios group (delta
      half-life = 10.3 +/- 13.07 minute, P = 0.034) but not in the Plac group (delta
      half-life = 0.53 +/- 15.51 minute, P = 0.086). The change over time of colloidal
      clearance was close to significance in the Dios group (delta clearance
      microL/minute: 2.18 +/- 3.10, P = 0.054) but not in the Plac group (0.11 +/-
      2.26, P = 0.86). No significant difference was found for evolution of lymphedema
      volume, despite a tendency in favor of Dios. This can be related to wide
      distribution of volume values and small numbers of patients. In conclusion, these
      results suggest a beneficial therapeutic activity of Dios at the usual dose of
      two tablets/day in patients affected with more severe lymphedema. The clear
      improvement of the lymphatic speed illustrates its known lymphokinetic activity.
      Further studies with a higher dosage could confirm the beneficial activity of
      this drug in secondary lymphedema.

PMID- 8995351
TI  - Additivity principles in biochemistry.

PMID- 8995352
TI  - The human delta1261 mutation of the HERG potassium channel results in a truncated
      protein that contains a subunit interaction domain and decreases the channel
      expression.
AB  - HERG (human eag-related gene) encodes an inward-rectifier potassium channel
      formed by the assembly of four subunits. Since the truncated HERG protein in
      patients with long QT syndrome induces a dominant phenotype, that is, cardiac
      sudden death, the assembly of nonfunctional complexes between wild-type and
      mutated subunits was implicated in causing the disease. To understand HERG
      mediated cardiac sudden death at the molecular level, it is important to
      determine which regions in the HERG protein participate in subunit interaction.
      We therefore report the identification of a subunit interaction domain,
      NAB(HERG), that is localized at the hydrophilic cytoplasmic N terminus and can
      form a tetramer in the absence of the rest of the HERG protein. Truncated HERG
      proteins containing NAB(HERG), including one that resulted from the delta1261
      human mutation, inhibit the functional expression of the HERG channel in
      transfected cells. Together, these results support the notion that the expression
      of HERG in the human heart may be decreased in the presence of the truncated
      subunit. Such a decrease of potassium channel expression can contribute to the
      longer QT intervals observed in the patients with the HERG mutation.

PMID- 8995353
TI  - Correction of defective protein kinesis of human P-glycoprotein mutants by
      substrates and modulators.
AB  - There is growing evidence that abnormal protein folding or trafficking (protein
      kinesis) leads to diseases. We have used P-glycoprotein as a model protein to
      develop strategies to overcome defects in protein kinesis. Misprocessed mutants
      of the human P-glycoprotein are retained in the endoplasmic reticulum as core
      glycosylated biosynthetic intermediates and rapidly degraded. Synthesis of the
      mutant proteins in the presence of drug substrates or modulators such as
      capsaicin, cyclosporin, vinblastine, or verapamil, however, resulted in the
      appearance of a fully glycosylated and functional protein at the cell surface.
      These effects were dose-dependent and occurred within a few hours after the
      addition of substrate. The ability to facilitate processing of the misfolded
      mutants appeared to be independent of the cell lines used and location of the
      mutation. P-glycoproteins with mutations in transmembrane segments, extracellular
      or cytoplasmic loops, the nucleotide-binding domains, or the linker region were
      processed to the fully mature form in the presence of these substrates. These
      drug substrates or modulators acted as specific chemical chaperones for P
      glycoprotein because they were ineffective on the deltaF508 mutant of cystic
      fibrosis transmembrane conductance regulator. Therefore, one possible strategy to
      prevent protein misfolding is to carry out synthesis in the presence of specific
      substrates or modulators of the protein.

PMID- 8995354
TI  - Characterization of the products of the heme detoxification pathway in malarial
      late trophozoites by X-ray diffraction.
AB  - In a process inhibited by the quinoline antimalarial drugs, Plasmodia detoxify
      heme released during the degradation of hemoglobin by aggregating it into
      malarial pigment, an insoluble crystalline heme coordination polymer. Synchrotron
      x-ray powder diffraction patterns for intact desiccated malarial trophozoites and
      synthetic beta-hematin have been measured; both materials correspond to a single
      crystalline triclinic lattice with unit cell parameters a = 12.2176(4), b =
      14.7184(5), c = 8.0456(3) A; alpha = 90.200(2), beta = 96.806(3), gamma =
      97.818(3) degrees and Z = 2. These results unambiguously demonstrate that
      hemozoin crystallites are identical to synthetic beta-hematin.

PMID- 8995355
TI  - Kinetic mechanism of a monomeric kinesin construct.
AB  - The kinetic mechanism is analyzed for a monomeric human kinesin construct K332.
      In the absence of microtubules, the rate constants of the ATPase cycle are very
      similar to dimeric human kinesin K379 and whole kinesin from bovine brain. The
      microtubule-activated ATPase is 60 s(-1) at 20 degrees C; Km(Mt) is 5 microM;
      dissociation constants in the presence of ATP and ADP are 9 microM and 16 microM,
      respectively. The values of dissociation constants are 5 times larger than for
      K379. Binding of K332 to microtubules increased the rate of the hydrolysis step
      from 7 s(-1) to greater than 200 s(-1) and the 2'-(3')-O-(N-methylanthraniloyl)
      (mant) ADP dissociation step from 0.02 s(-1) to greater than 100 s(-1). At higher
      ionic strength, more than one ATP is hydrolyzed before dissociation of MtK332
      (small processivity). Data are fitted to the kinetic scheme. [equation: see text]
      Approximate values of rate constants are k1 = 500 s(-1), k2 > or = 200 s(-1),
      k3k4/(k3 + k4) = 100 s(-1), k(dis) = 80+/-10 s(-1). Two experiments to measure k4
      gave 110 s(-1) from the maximum rate of dissociation of mant ADP for reaction of
      K x ADP with microtubules and 300 s(-1) from extrapolation to zero concentration
      of rate of binding of mant ADP to MtK. It is proposed that mant ADP dissociation
      is a two-step process. In the simple scheme, k4 is the effective rate of the two
      step release of ADP, k4 = 150 s(-1) to 200 s(-1), and k3 = 150 s(-1) to 200 s(-1)
      to account for the steady state rate.

PMID- 8995356
TI  - Interacting head mechanism of microtubule-kinesin ATPase.
AB  - Kinetic and equilibrium properties are compared for a monomeric kinesin construct
      (K332) and a dimeric construct (K379). MtK379 has a low affinity (5 x 10(4) M(
      1)) and a high affinity (5 x 10(6) M(-1)) binding site for mant ADP while MtK332
      has a single low affinity site (5 x 10(4) M(-1)). Rate constants of dissociation
      of mant ADP are <1 s(-1) for the high affinity site and 75-100 s(-1) for the low
      affinity site for MtK379. For MtK332, the effective rate constant is 200-300 s(
      1). It is proposed that the two heads of the dimer are different through the
      interaction with the microtubule, a strongly bound head with low affinity for 2'
      (3')-O-(N-methylanthraniloyl) adenosine 5'-diphosphate (mant ADP), similar to the
      single strongly bound head of the monomer and a weakly bound or detached head
      with high affinity for mant ADP. Rate of binding of mant ADP gave an "S"-shaped
      dependence on concentration for MtK379 and a hyperbolic dependence for MtK332.
      Binding of K379 x mant ADP dimer to microtubules releases only one mant ADP at a
      rate of 50 s(-1). The second strongly bound mant ADP is released by binding of
      nucleotides to the other head. Rates are 100 s(-1) for ATP, 30 s(-1) for AMPPNP
      or ATPgammaS, and 2 s(-1) for ADP. The rate of binding of mant ATP to MtK379
      showed an "S"-shaped concentration dependence and limiting rate at zero
      concentration is <1 s(-1) while MtK332 gave a hyperbolic dependence and limiting
      rate of 100 s(-1). The limiting rate is determined by the rate of dissociation of
      mant ADP in the hydrolysis cycle. The evidence is consistent with an interacting
      site model in which binding of ATP to one head is required for release of ADP
      from the other head in the hydrolysis cycle. This model, in which the cycles are
      maintained partly out of phase, is an extension of the alternating site model of
      Hackney (Hackney, D. D. (1994) Proc. Nat. Acad. Sci. U.S.A. 91, 6865-6869). It
      provides a basis for a processive mechanism.

PMID- 8995357
TI  - Ligand binding specificities of the two mannose 6-phosphate receptors.
AB  - Two mannose 6-phosphate (Man-6-P) receptors (MPRs) direct the vesicular transport
      of newly synthesized lysosomal enzymes that contain Man-6-P from the Golgi to a
      prelysosomal compartment. In order to understand the respective roles of the Mr =
      46,000 cation-dependent (CD-) MPR and the Mr = 300,000 cation-independent (CI-)
      MPR in lysosomal targeting, an assay has been developed that simultaneously
      measures the relative affinity of each MPR for multiple ligands. Glycoproteins
      containing Man-6-P were affinity-purified from the metabolically labeled
      secretions of mutant mouse fibroblasts lacking both MPRs. They were incubated
      with purified MPRs, and the resulting receptor-ligand complexes were
      immunoprecipitated by anti-MPR monoclonal antibodies coupled to agarose beads.
      Ligands were eluted with Man-6-P and then quantified following SDS-polyacrylamide
      gel electrophoresis. Saturating concentrations of CI-MPR resulted in the complete
      recovery of each Man-6-P glycoprotein in receptor-ligand complexes. Apparent
      affinity constants ranged between 1 and 5 nM for the individual species. Ligands
      precipitated by the CD-MPR appeared identical to those bound by the CI-MPR, with
      apparent affinity constants ranging between 7 and 28 nM. The binding affinities
      of the two receptors for different ligands were not correlated, indicating that
      the two MPRs preferentially recognize different subsets of lysosomal enzymes. In
      addition, saturating levels of CD-MPR resulted in the precipitation of only 50%
      of the total input ligands, suggesting that the CD-MPR binds a subpopulation of
      the Man-6-P glycoproteins bound by the CI-MPR. These results provide a
      biochemical mechanism, which, in part, may explain the interaction of the two
      MPRs with overlapping yet distinct subsets of ligands in vivo.

PMID- 8995358
TI  - Phosphorylation of Cbl following stimulation with interleukin-3 and its
      association with Grb2, Fyn, and phosphatidylinositol 3-kinase.
AB  - We have demonstrated that a 120-kDa protein, identified as Cbl, becomes rapidly
      phosphorylated on tyrosine residues following stimulation of factor-dependent
      cells with interleukin-3 (IL-3). Little or no phosphorylation of Cbl was observed
      in the absence of IL-3 stimulation and phosphorylation is maximal by 20-30 min
      after IL-3 stimulation. Association of Cbl with Grb2 was noted in unstimulated
      cells, and the amount of Cbl associated with Grb2 increased following IL-3
      stimulation. The p85 subunit of phosphatidylinositol 3-kinase was constitutively
      associated with Cbl. Approximately 10% of the PI kinase activity present in anti
      phosphotyrosine immunoprecipitates was present in anti-Cbl immunoprecipitates of
      IL-3-stimulated cells. The constitutive association of Cbl with Fyn was also
      observed. Cbl was observed to bind to bacterial fusion proteins encoding the
      unique, SH3, and SH2 domains of Fyn, Hck, and Lyn. The SH2 domain of Fyn alone
      was able to bind Cbl to nearly the same extent as did the fusion protein encoding
      the unique, SH3, and SH2 domains. This was not the case for the SH2 domain of
      Hck, however, as binding of the Hck fusion protein to Cbl appeared to require
      multiple domains. The binding of the fusion proteins to Cbl occurred regardless
      of whether Cbl was tyrosine-phosphorylated or not, and the binding could not be
      disrupted by the addition of 30 mM free phosphotyrosine. These data suggest the
      unexpected conclusion that the Fyn SH2 domain may bind to Cbl in a
      phosphotyrosine-independent manner.

PMID- 8995359
TI  - Identification of sulfhydryl-modified cysteine residues in the ligand binding
      pocket of retinoic acid receptor beta.
AB  - The diverse biological functions of retinoic acid (RA) are mediated through
      retinoic acid receptors (RARs) and retinoid X receptors. RARs contain a high
      affinity binding site for RA which is sensitive to treatment with sulfhydryl
      modification reagents. In an attempt to identify which Cys residues are important
      for this loss of binding, we created three site-specific RARbeta mutants: C228A,
      C258A, and C267A. The affinity for RA of all three mutant receptors was in the
      range of that of the wild type protein, suggesting that none of these Cys
      residues are critical for RA binding. Rather, these modified Cys residue(s)
      function to sterically hinder RA binding; however, the modified Cys residues
      critical for the inhibition of binding differ depending on the reagent employed.
      Only modification of Cys228 is necessary to inhibit RA binding when RARbeta is
      modified by reagents which transfer large bulky groups while both Cys228 and
      Cys267 must be modified when a small functional group is transferred. These data
      suggest that both Cys228 and Cys267 but not Cys258 lie in the ligand binding
      pocket of RARbeta. However, Cys228 lies closer to the opening of the RARbeta
      ligand binding pocket whereas Cys267 lies more deeply buried.

PMID- 8995360
TI  - Interruption of Escherichia coli heat-stable enterotoxin-induced guanylyl cyclase
      signaling and associated chloride current in human intestinal cells by 2
      chloroadenosine.
AB  - Diarrhea induced by Escherichia coli heat-stable enterotoxin (STa) is mediated by
      a receptor guanylyl cyclase cascade. The present study establishes that an
      intracellular nucleotide-dependent pathway disrupts toxin-induced cyclic GMP
      (cGMP) production and the associated chloride (Cl-) flux that underlie intestinal
      secretion. Incubation of Caco 2 human intestinal epithelial cells with the
      nucleoside analog 2-chloroadenosine (2ClAdo) resulted in a concentration- and
      time-dependent inhibition of toxin-induced cGMP production. Inhibition of cGMP
      production correlated with the metabolic conversion of 2ClAdo to 2
      chloroadenosine triphosphate. The effect of 2ClAdo did not reflect activation of
      adenosine receptors, inhibition of adenosine deaminase, or modification of the
      binding or distribution of STa receptors. Guanylyl cyclase activity in membranes
      prepared from 2ClAdo-treated cells was inhibited, in contrast to membranes from
      cells not exposed to 2ClAdo, demonstrating that inhibition of guanylyl cyclase C
      (GCC) was mediated by a noncompetitive mechanism. Treatment of Caco 2 cells with
      2ClAdo also prevented STa-induced Cl- current. Application of 8-bromo-cGMP, the
      cell-permeant analog of cGMP, to 2ClAdo-treated cells reconstituted the Cl-
      current, demonstrating that inhibition of Cl- flux reflected selective disruption
      of ligand stimulation of GCC rather than the chloride channel itself. Thus, the
      components required for adenine nucleotide inhibition of GCC signaling are
      present in intact mammalian cells, establishing the utility of this pathway to
      elucidate the mechanisms regulating ST-dependent guanylyl cyclase signaling and
      intestinal fluid homeostasis. In addition, these data suggest that the adenine
      nucleotide inhibitory pathway may be a novel target to develop antisecretory
      therapy for enterotoxigenic diarrhea.

PMID- 8995361
TI  - Depletion of human monocyte 85-kDa phospholipase A2 does not alter leukotriene
      formation.
AB  - Human monocytes possess several acylhydrolase activities and are capable of
      producing both prostanoids (PG) and leukotriene (LT) products upon acute
      stimulation with calcium ionophore, A23187 or phagocytosis of zymosan particles.
      The cytosolic 85-kDa phospholipase (PLA) A2 co-exists with the 14-kDa PLA2 in the
      human monocyte, but their respective roles in LT production are not well
      understood. Reduction in 85-kDa PLA2 cellular protein levels by initiation site
      directed antisense (SK 7111) or exposure to the 85-kDa PLA2 inhibitor,
      arachidonyl trifluoromethyl ketone (AACOCF3), prevented A23187 or zymosan
      stimulated monocyte prostanoid formation. In contrast, neither treatment altered
      stimulated LTC4 production. This confirmed the important role of the 85-kDa PLA2
      in prostanoid formation but suggests that it has less of a role in LT
      biosynthesis. Alternatively, treatment of monocytes with the selective, active
      site-directed 14-kDa PLA2 inhibitor, SB 203347, prior to stimulation had no
      effect on prostanoid formation at concentrations that totally inhibited LT
      formation. Addition of 20 microM exogenous arachidonic acid to monocytes exposed
      to SK 7111 or SB 203347 did not alter A23187-induced PGE2 or LTC4 generation,
      respectively, indicating that these agents had no effect on downstream
      arachidonic acid-metabolizing enzymes in this setting. Taken together, these
      results provide evidence that the 85-kDa PLA2 may play a more significant role in
      the formation of PG than LT. Further, utilization of SB 203347 provides
      intriguing data to form the hypothesis that a non-85-kDa PLA2 sn-2 acyl
      hydrolase, possibly the 14-kDa PLA2, may provide substrate for LT formation.

PMID- 8995362
TI  - Mutation of tryptophan residues in lipoprotein lipase. Effects on stability,
      immunoreactivity, and catalytic properties.
AB  - Previous studies had pointed to an important function of a putative exposed loop
      in the C-terminal domain of lipoprotein lipase for activity against emulsified
      lipid substrates. This loop contains 3 tryptophan residues (Trp390, Trp393, and
      Trp394). We have expressed and characterized lipase mutants with tryptophan to
      alanine substitutions at positions 55, 114, 382, 390, 393, and 394 and a double
      mutant at residues 393 and 394. The substitutions in the N-terminal domain (W55A
      and W114A) led to poor expression of completely inactive lipase variants. Heparin
      Sepharose chromatography showed that mutant W114A eluted at the same salt
      concentration as inactive wild-type monomers, indicating that this substitution
      prevented subunit interaction or led to an unstable dimer. In contrast, all
      mutants in the C-terminal domain were expressed as mixtures of monomers and
      dimers similarly to the wild-type. The dimers displayed at least some catalytic
      activity and had the same apparent heparin affinity as the active wild-type
      dimers. The mutants W390A, W393A, W394A, and W393A/W394A had decreased reactivity
      with the monoclonal antibody 5D2, indicating that the 5D2 epitope is longer than
      was reported earlier, or that conformational changes affecting the epitope had
      occurred. The mutants W390A, W393A, W394A, and W393A/W394A had decreased
      catalytic activity against a synthetic lipid emulsion of long-chain
      triacylglycerols (IntralipidR) and in particular against rat lymph chylomicrons.
      The most pronounced decrease of activity was found for the double mutant
      W393A/W394A which retained only 6% of the activity of the wild-type lipase, while
      70% of the activity against water-soluble tributyrylglycerol was retained. In the
      case of chylomicrons also the affinity for the substrate particles was lowered,
      as indicated by severalfold higher apparent Km values. This effect was less
      prominent with the synthetic lipid emulsion. We conclude that the tryptophan
      cluster Trp390-Trp393-Trp394 contributes to binding of lipoprotein lipase to
      lipid/water interfaces. Utilizing different lipid substrates in different
      physical states, we have demonstrated that the tryptophan residues in the C
      terminal domain may have a role also in the productive orientation of the enzyme
      at the lipid/water interface.

PMID- 8995363
TI  - The heterotrimeric G protein G alpha i2 mediates lysophosphatidic acid-stimulated
      induction of the c-fos gene in mouse fibroblasts.
AB  - Lysophosphatidic acid (LPA) utilizes a heterotrimeric guanine nucleotide
      regulatory (G) protein-coupled receptor to activate the mitogen-activated protein
      kinase pathway and induce mitogenesis in fibroblasts and other cells. A single
      cell assay system was used to examine the functional interaction of the LPA
      receptor with G proteins in intact mouse fibroblasts, by measuring LPA-stimulated
      induction of the immediate-early gene, c-fos, as read out by a stably expressed
      fos-lacZ reporter gene. Pretreatment of these cells with pertussis toxin at 100
      ng/ml almost completely abolished LPA-stimulated c-fos induction. Western
      blotting revealed that two pertussis toxin (PTX)-sensitive G proteins, G alpha i2
      and G alpha i3, were present in membranes prepared from these cells, and Northern
      blotting confirmed the absence of message for other PTX-sensitive subunits.
      Microinjection of an alpha il/alpha i2-specific antibody into living cells
      decreased LPA-stimulated induction of c-fos by 60%, whereas introduction of
      antibodies to either alpha i3 or alpha 16, a subtype not present in these cells
      but used as a control, decreased LPA-stimulated c-fos induction by only 19%. In
      contrast, the alpha i1/alpha i2-specific antibody had no effect on insulin
      induced c-fos expression, which is thought to utilize a G protein-independent
      mechanism of signaling. In addition, cellular expression of an epitope-tagged PTX
      resistant mutant of G alpha i2, but not PTX-resistant G alpha i3, restored LPA
      stimulated c-fos induction in cells in which endogenous G protein a subunits were
      uncoupled from the receptor by pretreatment with PTX. Together, these results
      provide conclusive in vivo evidence that G alpha i2 is the PTX-sensitive G
      protein a subunit which mediates LPA-stimulated c-fos induction and perhaps
      mitogenesis in these cells.

PMID- 8995364
TI  - Differential opioid agonist regulation of the mouse mu opioid receptor.
AB  - Mu opioid receptors mediate the analgesia induced by morphine. Prolonged use of
      morphine causes tolerance development and dependence. To investigate the
      molecular basis of tolerance and dependence, the cloned mouse mu opioid receptor
      with an amino-terminal epitope tag was stably expressed in human embryonic kidney
      (HEK) 293 cells, and the effects of prolonged opioid agonist treatment on
      receptor regulation were examined. In HEK 293 cells the expressed mu receptor
      showed high affinity, specific, saturable binding of radioligands and a pertussis
      toxin-sensitive inhibition of adenylyl cyclase. Pretreatment (1 h, 3 h, or
      overnight) of cells with 1 microM morphine or [D-Ala2MePhe4,Gly(ol)5]enkephalin
      (DAMGO) resulted in no apparent receptor desensitization, as assessed by opioid
      inhibition of forskolin-stimulated cAMP levels. In contrast, the morphine and
      DAMGO pretreatments (3 h) resulted in a 3-4-fold compensatory increase in
      forskolin-stimulated cAMP accumulation. The opioid agonists methadone and
      buprenorphine are used in the treatment of addiction because of a markedly lower
      abuse potential. Pretreatment of mu receptor-expressing HEK 293 cells with
      methadone or buprenorphine abolished the ability of opioids to inhibit adenylyl
      cyclase. No compensatory increase in forskolin-stimulated cAMP accumulation was
      found with methadone or buprenorphine; these opioids blocked the compensatory
      effects observed with morphine and DAMGO. Taken together, these results indicate
      that methadone and buprenorphine interact differently with the mouse mu receptor
      than either morphine or DAMGO. The ability of methadone and buprenorphine to
      desensitize the mu receptor and block the compensatory rise in forskolin
      stimulated cAMP accumulation may be an underlying mechanism by which these agents
      are effective in the treatment of morphine addiction.

PMID- 8995365
TI  - Inhibition of myogenesis by multiple cyclin-Cdk complexes. Coordinate regulation
      of myogenesis and cell cycle activity at the level of E2F.
AB  - During skeletal myogenesis, cell cycle withdrawal accompanies the expression of
      the contractile phenotype. Here we show that ectopic expression of each D-type
      cyclin is sufficient to inhibit the transcriptional activation of the muscle
      specific creatine kinase (MCK) gene. In contrast, ectopic expression of cyclin A
      or cyclin E inhibits MCK expression only when they are co-expressed with their
      catalytic partner cyclin-dependent kinase 2 (Cdk2). For each of these conditions,
      myogenic transcriptional inhibition is reversed by the ectopic co-expression of
      the general Cdk inhibitor p21. Inhibition of MCK expression by cyclins or cyclin
      Cdk combinations correlates with E2F activation, suggesting that the inhibition
      is mediated by the overall Rb-kinase activities of the Cdk complexes. In support
      of this hypothesis, a hyperactive mutant of Rb was found to partially reverse the
      inhibition of MCK expression by cyclin D1 and by the combination of cyclin A and
      Cdk2. These data demonstrate that the inhibition of myogenic transcriptional
      activity is a general feature of overall Cdk activity which is mediated, at least
      in part, by an pocket protein/E2F-dependent pathway. MCK promoter activity is
      also inhibited by ectopic E2F1 expression, but this inhibition is not reversed by
      the co-expression of p21. Analyses of a series of E2F1 mutants revealed that the
      transcriptional activation, leucine zipper, basic, and cyclin A/Cdk2-binding
      domains are dispensable, but the helix-loop-helix region is essential for
      myogenic inhibition. These data demonstrate that myocyte proliferation and
      differentiation are coordinated at the level of E2F and that these opposing
      activities are regulated by different E2F domains.

PMID- 8995366
TI  - Polymerase chain reaction-based cloning of alkyl-dihydroxyacetonephosphate
      synthase complementary DNA from guinea pig liver.
AB  - Peroxisomes are indispensable organelles for ether lipid biosynthesis in
      mammalian tissues, and the deficiency of these organelles in a number of
      peroxisomal disorders leads to deficiencies in ether phospholipids. We have
      previously purified the committed enzyme for ether lipid biosynthesis, i.e. alkyl
      dihydroxyacetone-phosphate synthase, to homogeneity. We have now determined the N
      terminal amino acid sequence, as well as additional internal sequences obtained
      after cyanogen bromide cleavage of the enzyme. With primers directed against the
      N-terminal sequence and against a cyanogen bromide fragment sequence, a 1100-bp
      cDNA fragment was obtained by conventional polymerase chain reaction using first
      strand cDNA from guinea pig liver as a template. The 5' and 3' ends of the cDNA
      were obtained by rapid amplification of cDNA ends. The open reading frame encodes
      a protein of 658 amino acids, containing the N-terminal amino acid sequence as
      well as the cyanogen bromide cleavage fragment sequences. The derived amino acid
      sequence includes a mature protein 600 amino acids long and a presequence 58
      amino acids long. The latter contains a stretch of amino acids known as
      peroxisomal targeting signal 2. The size of the mRNA was estimated to be around
      4200 nucleotides. Recombinant His-tagged alkyl-dihydroxyacetonephosphate synthase
      expressed in Escherichia coli was enzymatically active.

PMID- 8995367
TI  - Heterologous expression, isolation, and characterization of versicolorin B
      synthase from Aspergillus parasiticus. A key enzyme in the aflatoxin B1
      biosynthetic pathway.
AB  - Aflatoxin B1 is a potent environmental carcinogen produced by certain strains of
      Aspergillus. Central to the biosynthesis of this mycotoxin is the reaction
      catalyzed by versicolorin B synthase (VBS) in which a racemic substrate,
      versiconal hemiacetal, is cyclized to an optically active product whose absolute
      configuration is crucial to the interaction of aflatoxin B1 with DNA. Attempted
      over-production of VBS in Escherichia coli led principally to protein aggregated
      into inclusion bodies but also small amounts of soluble but catalytically
      inactive enzyme. Comparisons to wild-type VBS by SDS-polyacrylamide gel
      electrophoresis and after N-glycosidase F treatment revealed that extensive
      glycosylation accounted for the mass discrepancy (7,000+/-1,500 Da) between the
      native and bacterially expressed proteins. Several over-expression systems in
      Saccharomyces cerevisiae were surveyed in which one that incorporated a secretion
      signal was found most successful. VBS of indistinguishable mass on SDS
      polyacrylamide gel electrophoresis and kinetic properties from the wild-type
      enzyme could be obtained in 50-100-fold greater amounts and whose catalytic
      behavior has been examined. The translated protein sequence of VBS showed three
      potential N-glycosylation sites (Asn-Xaa-Ser/Thr) consistent with the
      modifications observed above and unexpectedly revealed extensive homology to the
      ADP-binding region prominently conserved in the glucose-methanol-choline (GMC)
      family of flavoenzymes. Over-production of VBS in yeast marks the first aflatoxin
      biosynthetic enzyme to be so obtained and opens the way to direct study of the
      enzymology of this complex biosynthetic pathway.

PMID- 8995368
TI  - Identification of candidate active site residues in lysosomal beta-hexosaminidase
      A.
AB  - The beta-hexosaminidases (Hex) catalyze the cleavage of terminal amino sugars on
      a broad spectrum of glycoconjugates. The major Hex isozymes in humans, Hex A, a
      heterodimer of alpha and beta subunits (alphabeta), and Hex B, a homodimer of
      beta subunits (betabeta), have different substrate specificities. The beta
      subunit (HEXB gene product), hydrolyzes neutral substrates. The alpha subunit
      (HEXA gene product), hydrolyzes both neutral and charged substrates. Only Hex A
      is able to hydrolyze the most important natural substrate, the acidic glycolipid
      GM2 ganglioside. Mutations in the HEXA gene cause Tay-Sachs disease (TSD), a GM2
      ganglioside storage disorder. We investigated the role of putative active site
      residues Asp-alpha258, Glu-alpha307, Glu-alpha323, and Glu-alpha462 in the alpha
      subunit of Hex A. A mutation at codon 258 which we described was associated with
      the TSD B1 phenotype, characterized by the presence of normal amounts of mature
      but catalytically inactive enzyme. TSD-B1 mutations are believed to involve
      substitutions of residues at the enzyme active site. Glu-alpha307, Glu-alpha323,
      and Glu-alpha462 were predicted to be active site residues by homology studies
      and hydrophobic cluster analysis. We used site-directed mutagenesis and
      expression in a novel transformed human fetal TSD neuroglial (TSD-NG) cell line
      (with very low levels of endogenous Hex A activity), to study the effects of
      mutation at candidate active site residues. Mutant HEXA cDNAs carrying
      conservative or isofunctional substitutions at these positions were expressed in
      TSD-NG cells. alphaE323D, alphaE462D, and alphaD258N cDNAs produced normally
      processed peptide chains with drastically reduced activity toward the alpha
      subunit-specific substrate 4MUGS. The alphaE307D cDNA produced a precursor
      peptide with significant catalytic activity. Kinetic analysis of enzymes carrying
      mutations at Glu-alpha323 and Asp-alpha258 (reported earlier by Bayleran, J.,
      Hechtman, P., Kolodny, E., and Kaback, M. (1987) Am. J. Hum. Genet. 41,532-548)
      indicated no significant change in substrate binding properties. Our data, viewed
      in the context of homology studies and modeling, and studies with suicide
      substrates, suggest that Glu-alpha323 and Asp-alpha258 are active site residues
      and that Glu-alpha323 is involved in catalysis.

PMID- 8995369
TI  - Synaptic membrane glycoproteins gp65 and gp55 are new members of the
      immunoglobulin superfamily.
AB  - Glycoproteins gp65 and gp55 are major components of synaptic membranes prepared
      from rat forebrain. Both are recognized by the monoclonal antibody SMgp65. We
      have used SMgp65 to screen a rat brain cDNA expression library. Two sets of
      overlapping cDNAs that contain open reading frames of 397 and 281 amino acids
      were isolated. The deduced proteins are members of the immunoglobulin (Ig)
      superfamily containing three and two Ig domains, respectively. The common part
      has approximately 40% sequence identity with neurothelin/basigin. The identity of
      the proteins as gp65 and gp55 was confirmed by production of new antisera against
      a common recombinant protein fragment. These antisera immunoprecipitate gp65 and
      gp55. Furthermore, expression of gp65 and gp55 cDNAs in human 293 cells treated
      with tunicamycin results in the production of unglycosylated core proteins of
      identical size to deglycosylated gp65 and gp55. Northern analysis revealed that
      gp65 transcripts are brain-specific, whereas gp55 is expressed in most tissues
      and cell lines examined. The tissue distribution was confirmed at the protein
      level though the pattern of glycosylation of gp55 varies between tissues. In situ
      hybridization experiments with a common and a gp65-specific probe suggest
      differential expression of gp65 and gp55 transcripts in the rat brain.

PMID- 8995370
TI  - Autophosphorylation of Dictyostelium myosin II heavy chain-specific protein
      kinase C is required for its activation and membrane dissociation.
AB  - Myosin II heavy chain (MHC)-specific protein kinase C (MHC-PKC) isolated from the
      ameba, Dictyostelium discoideum, regulates myosin II assembly and localization in
      response to the chemoattractant cAMP. cAMP stimulation of Dictyostelium cells
      leads to translocation of MHC-PKC from the cytosol to the membrane fraction, as
      well as causing an increase in both MHC-PKC phosphorylation and its kinase
      activity. MHC-PKC undergoes autophosphorylation with each mole of kinase
      incorporating about 20 mol of phosphate. The MHC-PKC autophosphorylation sites
      are thought to be located within a domain at the COOH-terminal region of MHC-PKC
      that contains a cluster of 21 serine and threonine residues. Here we report that
      deletion of this domain abolished the ability of the enzyme to undergo
      autophosphorylation in vitro. Furthermore, after this deletion, cAMP-dependent
      autophosphorylation of MHC-PKC as well as cAMP-dependent increases in kinase
      activity and subcellular localization were also abolished. These results provide
      evidence for the role of autophosphorylation in the regulation of MHC-PKC and
      indicate that this MHC-PKC autophosphorylation is required for the kinase
      activation in response to cAMP and for subcellular localization.

PMID- 8995371
TI  - Dentin phosphoprotein and dentin sialoprotein are cleavage products expressed
      from a single transcript coded by a gene on human chromosome 4. Dentin
      phosphoprotein DNA sequence determination.
AB  - Dentin is the major mineralized extracellular matrix of the tooth. The organic
      components of dentin consist of type I collagen (90%) with 10% noncollagenous
      proteins, which are also components of bone. Two dentin proteins, dentin
      sialoprotein and dentin phosphoprotein, have been shown to be tooth-specific
      being expressed mostly by odontoblast cells. In this study, we screened a mouse
      molar tooth library for dentin sialoprotein and dentin phosphoprotein cDNA
      clones. Analysis of the clones resulted in characterization of a 4420-nucleotide
      cDNA that contained a 940-amino acid open reading frame. The signal peptide and
      NH2-terminal sequence was 75% homologous to the cDNA sequence of rat dentin
      sialoprotein. The continued open reading frame, however, contained a RGD sequence
      followed by a region of repeated aspartic acid and serine residues. This portion
      of the protein codes for amino acid sequence consistent with that of dentin
      phosphoprotein. The noncoding region contains three potential polyadenylation
      signals, two of which were shown to be utilized. Northern blot analysis indicated
      the presence of two major transcripts of 4.4 and 2.2 kilobases in odontoblasts.
      Chromosomal mapping localized the gene to human chromosome 4. These data suggest
      that the previously identified dentin extracellular matrix proteins, dentin
      sialoprotein and dentin phosphoprotein, are expressed as a single cDNA transcript
      coding for a protein that is specifically cleaved into two smaller polypeptides
      with unique physical-chemical characteristics. Therefore, we propose that the
      gene be named dentin sialophosphoprotein. The location of the human dentin
      sialophosphoprotein gene on chromosome 4 suggests that this gene may be a strong
      candidate gene for the genetic disease dentinogenesis imperfecta type II.

PMID- 8995372
TI  - Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and
      pervanadate.
AB  - Vanadate and pervanadate (the complexes of vanadate with hydrogen peroxide) are
      two commonly used general protein-tyrosine phosphatase (PTP) inhibitors. These
      compounds also have insulin-mimetic properties, an observation that has generated
      a great deal of interest and study. Since a careful kinetic study of the two
      inhibitors has been lacking, we sought to analyze their mechanisms of inhibition.
      Our results show that vanadate is a competitive inhibitor for the protein
      tyrosine phosphatase PTP1B, with a Ki of 0.38+/-0.02 microM. EDTA, which is known
      to chelate vanadate, causes an immediate and complete reversal of the inhibition
      due to vanadate when added to an enzyme assay. Pervanadate, by contrast, inhibits
      by irreversibly oxidizing the catalytic cysteine of PTP1B, as determined by mass
      spectrometry. Reducing agents such as dithiothreitol that are used in PTP assays
      to keep the catalytic cysteine reduced and active were found to convert
      pervanadate rapidly to vanadate. Under certain conditions, slow time-dependent
      inactivation by vanadate was observed; since catalase blocked this inactivation,
      it was ascribed to in situ generation of hydrogen peroxide and subsequent
      formation of pervanadate. Implications for the use of these compounds as
      inhibitors and rationalization for some of their in vivo effects are considered.

PMID- 8995373
TI  - The phosphorylation pattern of oligosaccharides in secreted procathepsin D is
      glycosylation site-specific and independent of the expression of mannose 6
      phosphate receptors.
AB  - Mammalian cells contain two types of mannose 6-phosphate receptors (MPR), MPRs 46
      and 300, that contribute with variable efficiency to the sorting of individual
      lysosomal proteins. To evaluate the role of phosphorylated oligosaccharides for
      the sorting efficiency by either of the two receptors, the structure of
      phosphorylated oligosaccharides on lysosomal proteins escaping sorting in cells
      lacking MPR 46 and/or MPR 300 was analyzed. Procathepsin D was chosen as a model
      because it is sorted efficiently via MPR 300 and poorly via MPR 46 and contains a
      distinct and highly heterogenous mixture of phosphorylated oligosaccharides at
      either of its two N-glycosylation sites. Both MPRs 46 and 300 were found to have
      a minor but distinct preference for forms of procathepsin D and other lysosomal
      proteins containing oligosaccharides with two phosphomonoesters. However, the
      phosphorylation of oligosaccharides in procathepsin D and other lysosomal
      proteins that escape sorting in control cells or in cells lacking MPR 46 and/or
      MPR 300 was strikingly similar, and oligosaccharides with two phosphomonoesters
      represented the major oligosaccharide species. We conclude from these results
      that the position of the position of the phosphate groups, the structure of the
      underlying oligosaccharide, and/or the polypeptide backbone of lysosomal proteins
      have major roles in determining the affinity to MPRs.

PMID- 8995374
TI  - Characterization of transport through the periplasmic histidine permease using
      proteoliposomes reconstituted by dialysis.
AB  - The superfamily of traffic ATPases (ABC transporters) includes bacterial
      periplasmic transport systems (permeases) and various eukaryotic transporters.
      The histidine permease of Salmonella typhimurium and Escherichia coli is composed
      of a membrane-bound complex containing four subunits and of a soluble receptor,
      the substrate-binding protein (HisJ), and is energized by ATP. The permease was
      previously reconstituted into proteoliposomes by a detergent dilution method (1).
      Here we extensively characterize the properties of this permease after
      reconstitution into proteoliposomes by dialysis and encapsulation of ATP or other
      reagents by freeze-thawing. We show that histidine transport depends entirely on
      both ATP and liganded HisJ, with apparent Km values of 8 mM and 8 microM,
      respectively, and is affected by pH, temperature, and salt concentration.
      Transport is irreversible and accumulation reaches a plateau at which point
      transport ceases. The permease is inhibited by ADP and by high concentrations of
      internal histidine. The inhibition by histidine implies that the membrane-bound
      complex HisQ/M/P carries a substrate-binding site. The reconstituted permease
      activity corresponds to about 40-70% turnover rate of the in vivo rate of
      transport.

PMID- 8995375
TI  - Tracer studies with crude U-13C-lipid mixtures. Biosynthesis of the lipase
      inhibitor lipstatin.
AB  - The biosynthesis of the pancreatic lipase inhibitor lipstatin was investigated by
      fermentation experiments using cultures of Streptomyces toxytricini, which were
      supplied with soybean oil and a crude mixture of U-13C-lipids obtained from algal
      biomass cultured with 13CO2. Lipstatin was analyzed by one- and two-dimensional
      NMR spectroscopy. 13C total correlation spectroscopy and INADEQUATE experiments
      show that two fatty acid fragments containing 14 and 8 carbon atoms,
      respectively, are incorporated en bloc into lipstatin. The 14-carbon fragment is
      preferentially derived from the unsaturated fatty acid fraction, as shown by an
      experiment with hydrogenated U-13C-lipid mixture, which is conducive to labeling
      of the 8-carbon moiety but not of the 14-carbon moiety. The data indicate that
      the lipstatin molecule can be assembled by Claisen condensation of octanoyl-CoA
      with 3-hydroxy-delta5,8-tetradecanoyl-CoA obtained by beta oxidation of linoleic
      acid. The formation of lipstatin from acetate units by a polyketide-type pathway
      is ruled out conclusively by these data. The data show that surprisingly clear
      labeling patterns can be obtained in studies with crude, universally 13C-labeled
      precursor mixtures that are proffered together with a large excess of unlabeled
      material. One- and two-dimensional 13C total correlation spectroscopy analyses
      are suggested as elegant methods for the delineation of contiguously 13C-labeled
      biosynthetic blocks.

PMID- 8995376
TI  - Regulation of Src homology 2-containing tyrosine phosphatase 1 during activation
      of human neutrophils. Role of protein kinase C.
AB  - The tyrosine phosphorylation of several proteins induced in neutrophils by
      soluble and particulate stimuli is thought to be crucial for initiating
      antimicrobial responses. Although activation of tyrosine kinases is thought to
      mediate this event, the role of tyrosine phosphatases in the initiation and
      modulation of neutrophil responses remains largely undefined. We investigated the
      role of Src homology 2-containing tyrosine phosphatase 1 (SHP-1; also known as
      protein tyrosine phosphatase 1C (PTP1C), hematopoetic cell phosphatase, PTP-N6,
      and SHPTP-1), a phosphatase expressed primarily in hemopoietic cells, in the
      activation of human neutrophils. SHP-1 mRNA and protein were detected in these
      cells, and the enzyme was found to be predominantly localized to the cytosol in
      unstimulated cells. Following stimulation with neutrophil agonists such as
      phorbol ester, chemotactic peptide, or opsonized zymosan, a fraction of the
      phosphatase redistributed to the cytoskeleton. Agonist treatment also induced
      significant decreases (30-60%) in SHP-1 activity, which correlated temporally
      with increases in the cellular phosphotyrosine content. Phosphorylation of SHP-1
      on serine residues was associated with the inhibition of its enzymatic activity,
      suggesting a causal relationship. Accordingly, both the agonist-evoked
      phosphorylation of SHP-1 and the inhibition of its catalytic activity were
      blocked by treatment with bisindolylmaleimide I, a potent and specific inhibitor
      of protein kinase C (PKC) activity. Immunoprecipitated SHP-1 was found to be
      phosphorylated efficiently by purified PKC in vitro. Such phosphorylation also
      caused a decrease in the phosphatase activity of SHP-1. Together, these data
      suggest that inhibition of SHP-1 by PKC-mediated serine phosphorylation plays a
      role in facilitating the accumulation of tyrosine-phosphorylated proteins
      following neutrophil stimulation. These findings provide a new link between the
      PKC and tyrosine phosphorylation branches of the signaling cascade that triggers
      antimicrobial responses in human neutrophils.

PMID- 8995377
TI  - Cloning of a carboxyl-terminal isoform of the prostanoid FP receptor.
AB  - An FP prostanoid receptor isoform, which appears to arise from alternative mRNA
      splicing, has been cloned from a mid-cycle ovine large cell corpus luteum
      library. The isoform, named the FP(B) receptor, is identical to the original
      isoform, the FP(A), throughout the seven transmembrane domains, but diverges nine
      amino acids into the carboxyl terminus. In contrast to FP(A), whose carboxyl
      terminus continues for another 46 amino acids beyond the nine shared residues,
      the FP(B) terminates after only one amino acid. The FP(A) isoform appears to
      arise by the failure to utilize a potential splice site, while a 3.2-kilobase
      pair intron is spliced out from the FP gene to generate the FP(B) isoform mRNA.
      The two isoforms have indistinguishable radioligand binding properties, but seem
      to differ in functional coupling to phosphatidylinositol hydrolysis. Thus, in COS
      7 cells transiently transfected with either the FP(A) or the FP(B) receptor
      cDNAs, prostaglandin F(2alpha) stimulates inositol phosphate accumulation to the
      same absolute maximum, but the basal level of inositol phosphate accumulation is
      approximately 1.3-fold higher in cells transfected with the FP(B) as compared
      with cells transfected with the FP(A) isoform. Using the polymerase chain
      reaction, mRNA encoding the FP(B) isoform was identified in the ovine corpus
      luteum.

PMID- 8995378
TI  - Heparin promotes proteolytic inactivation by thrombin of a reactive site mutant
      (L444R) of recombinant heparin cofactor II.
AB  - A heparin cofactor II (HCII) mutant with an Arg substituted for Leu444 at the P1
      position (L444R-rHCII) was previously found to have altered proteinase
      specificity (Derechin, V. M., Blinder, M. A., and Tollefsen, D. M. (1990) J.
      Biol. Chem. 265, 5623-5628). The present study characterizes the effect of
      glycosaminoglycans on the substrate versus inhibitor activity of L444R-rHCII.
      Heparin increased the stoichiometry of inhibition of L444R-rHCII with alpha
      thrombin (compared with minus glycosaminoglycan) but decreased it with
      R93A,R97A,R101A-thrombin, a mutant thrombin that does not bind
      glycosaminoglycans. Dermatan sulfate decreased the stoichiometry of inhibition of
      L444R-rHCII with both proteinases. SDS-polyacrylamide gel electrophoresis showed
      no proteolysis of L444R-rHCII when incubated with R93A,R97A,R101A-thrombin in the
      absence or the presence of glycosaminoglycan or with alpha-thrombin and dermatan
      sulfate. In contrast, greater than 75% of the L444R-rHCII was converted to a
      lower molecular weight form when incubated with alpha-thrombin/heparin. A time
      course of alpha-thrombin inhibition by L444R-rHCII/heparin showed a rapid but
      transient inhibition with approximately 80% of the alpha-thrombin activity being
      regained after 6 h of incubation. In contrast, all other combinations of
      inhibitor, proteinase, and glycosaminoglycan resulted in complete and sustained
      inhibition of the proteinase. Heparin fragments of 8-20 polysaccharides in length
      rapidly accelerated L444R-rHCII inhibition of both alpha-thrombin and
      R93A,R97A,R101A-thrombin. After extended incubations, R93A,R97A,R101A-thrombin
      was completely inhibited by L444R-rHCII with all the heparin fragments, but
      approximately 30-50% of alpha-thrombin activity remained with fragments long
      enough to bridge HCII-thrombin. These results collectively indicate that ternary
      complex formation, mediated by heparin, increases L444R-rHCII inactivation by
      alpha-thrombin.

PMID- 8995379
TI  - The role of a lymphoid-restricted, Grb2-like SH3-SH2-SH3 protein in T cell
      receptor signaling.
AB  - We have characterized an SH3-SH2-SH3 linker protein that is prominently expressed
      in lymphoid tissues. This protein has 58% sequence identity to Grb2. An identical
      protein called Grap has been found in hematopoietic cells. In Jurkat cells, T
      cell receptor activation leads to the association of Grap with phosphoproteins
      p36/38 and, to a lesser degree, Shc. This interaction is mediated by the Grap SH2
      domain, which has similar binding specificity to the Grb2 SH2 domain. Grap also
      associates via its SH3 domains with Sos, the Ras guanine nucleotide exchange
      factor; with dynamin, a GTPase involved in membrane protein trafficking; and with
      Sam68, a nuclear RNA-binding protein that serves as a substrate of Src kinases
      during mitosis. T cell activation effects an increase in Grap association with
      p36/38, Shc, Sos, and dynamin. Sam68 binding is constitutive. Phospholipase C
      gamma1 and Fyn are also found in activated Grap signaling complexes, although
      these interactions may not be direct. We conclude that Grap is a prominent
      component of lymphocyte receptor signaling. Based on the known functions of bound
      effector molecules, Grap-mediated responses to antigen challenge may include
      endocytosis of the T cell receptor, cellular proliferation, and regulated entry
      into the cell cycle.

PMID- 8995380
TI  - Identification, cloning, and characterization of cystatin M, a novel cysteine
      proteinase inhibitor, down-regulated in breast cancer.
AB  - A novel human cystatin gene was identified in a differential display comparison
      aimed at the isolation of transcriptionally regulated genes involved in invasion
      and metastasis of breast cancer. Messenger RNAs from primary and metastatic tumor
      cells isolated from the same patient were compared. A partial cDNA was isolated
      that was expressed in the primary tumor cell line but not in the metastatic line.
      The full-length cDNA was cloned and sequenced, and the inferred amino acid
      sequence was found to encode a novel protein, which we named cystatin M, with 40%
      homology to human family 2 cystatins and similar overall structure. Cystatin M is
      expressed by normal mammary cells and a variety of human tissues. The mature
      cystatin M protein was produced in Escherichia coli as a glutathione S
      transferase fusion protein using the pGEX-2T expression system and purified by
      affinity chromatography. The cystatin M fusion protein displayed inhibitory
      activity against papain. Native cystatin M protein of approximately 14.5 kDa is
      secreted and was immunoprecipitated from supernatants of mammary cell cultures
      using affinity-purified antisera raised against recombinant cystatin M. An N
      glycosylated form of cystatin M of 20-22 kDa was co-immunoprecipitated and
      accounted for about 30-40% of total cystatin M protein. Both forms of native
      cystatin M also occurred intracellularly. Consistent with the mRNA differential
      expression, no cystatin M protein was detected in metastatic mammary epithelial
      tumor cells. Loss of expression of cystatin M is likely associated with the
      progression of a primary tumor to a metastatic phenotype.

PMID- 8995381
TI  - Heteromultimeric complexes of CD40 ligand are present on the cell surface of
      human T lymphocytes.
AB  - CD40 ligand (CD40L), a 33-kDa type II membrane glycoprotein expressed primarily
      on activated CD4+ T lymphocytes, is responsible for the helper function of T
      cells on resting B cells in a non-antigen-dependent, non-major histocompatability
      complex-restricted fashion. Interaction of CD40L with its receptor CD40 induces
      proliferation of and isotype switching in B lymphocytes. Recently we solved the x
      ray structure of recombinant soluble CD40L and showed that, similar to other
      members of the tumor necrosis factor family, CD40L indeed exists as a trimer. We
      now report that, under normal physiological conditions, CD40L molecules exist as
      heteromultimeric complexes. These CD40L complexes, made of the full length and
      smaller fragments of CD40L, are present on the cell surface of T lymphocytes and
      are capable of interacting with CD40 molecule. A prominent fragment with a mass
      of 31 kDa accounts for as much as half of the CD40L on the surface of Jurkat
      cells. N-terminal sequence data revealed that this fragment lacks the cytoplasmic
      tail. A minor 18-kDa fragment of CD40L was also characterized which lacks the
      cytoplasmic tail, transmembrane region, and stalk region of the extracellular
      domain. The presence of CD40L heteromultimeric variants implies an additional
      regulation of the functional activity of this ligand complex.

PMID- 8995383
TI  - Effects of redox potential and hydroxide inhibition on the pH activity profile of
      fungal laccases.
AB  - The electronic absorption spectrum, susceptibility to fluoride inhibition, redox
      potential, and substrate turnover of several fungal laccases have been explored
      as a function of pH. The laccases showed a single spectrally detectable acid-base
      transition at pH 6-9 and a fluoride inhibition that diminished by increased pH
      (indicating a competition with hydroxide inhibition). Relatively small changes in
      the redox potentials (< or = 0.1 V) of laccase were observed over the pH 2.7-11.
      Under the catalysis of laccase, the apparent oxidation rates (kcat and kcat/Km)
      of two nonphenolic substrates, potassium ferrocyanide and 2,2'-azinobis-(3
      ethylbenzthiazoline-6-sulfonic acid), decreased monotonically as the pH
      increased. In contrast, the apparent oxidation rates (kcat and kcat/Km) of three
      2,6-dimethoxyphenols (whose pKa values range from 7.0 to 8.7) exhibited bell
      shaped pH profiles whose maxima were distinct for each laccase but independent of
      the substrate. By correlating these pH dependences, it is proposed that the
      balance of two opposing effects, one generated by the redox potential difference
      between a reducing substrate and the type 1 copper of laccase (which correlates
      to the electron transfer rate and is favored for a phenolic substrate by higher
      pH) and another generated by the binding of a hydroxide anion to the type 2/type
      3 coppers of laccase (which inhibits the activity at higher pH), contributes to
      the pH activity profile of the fungal laccases.

PMID- 8995382
TI  - Phosphorylation of linker histones by a protein kinase A-like activity in mitotic
      nuclei.
AB  - Micronuclear linker histones of the ciliated protozoan, Tetrahymena thermophila,
      are extensively phosphorylated in vivo. Each of these polypeptides, alpha, beta,
      gamma, and delta, contains sites for phosphorylation by cyclic-AMP dependent
      protein kinase (PKA) but not Cdc2 kinase, and some data have been presented
      implicating PKA kinase in their phosphorylation in vitro and in vivo (Sweet, M.
      T., and Allis, C. D. (1993) Chromosoma 102, 637-647; Sweet, M. T., Jones, K., and
      Allis, C. D. (1996) J. Cell Biol., in press). In this report we have extended
      these analyses by showing that Cdc2 and PKA kinase are not evenly distributed
      between micro- and macronuclei. Macronuclei, but not micronuclei, contain a 36
      kDa polypeptide that is immunoreactive with p34Cdc2 antibodies. In contrast, a 40
      kDa polypeptide is detected with PKA antibodies in micronuclei, that is not
      detected in macronuclei. In support, extracts from micronuclei, but not
      macronuclei, contain a kinase activity that resembles some, but not all,
      characteristics of PKA from other sources. Immunodepletion experiments using anti
      PKA antibodies show that a 40-kDa polypeptide can be specifically removed from
      these extracts with a concomitant loss in kinase activity. Microsequence analyses
      of delta demonstrate that this linker histone is phosphorylated in vivo on two
      PKA consensus sequences located in its carboxyl-terminal domain, an optimum PKA
      consensus sequence, Arg-Lys-Asn-Ser, and a less optimal PKA sequence, Lys-Ser-Ser
      Val. Collectively, these results suggest that PKA or a PKA-like kinase is
      responsible for the phosphorylation of linker histone in mitotically dividing
      micronuclei. In contrast, macronuclei, which divide amitotically, phosphorylate
      linker histone H1 using a distinct, Cdc2-like kinase.

PMID- 8995384
TI  - Lipid dependence and basic kinetics of the purified 1,2-diacylglycerol 3
      glucosyltransferase from membranes of Acholeplasma laidlawii.
AB  - UDP-glucose: 1,2-diacylglycerol 3-glucosyltransferase (EC 2.4.1.157), catalyzes
      the transfer of glucose from UDP-glucose to diacylglycerol (DAG) to yield
      monoglucosyldiacylglycerol (MGlcDAG) and UDP. MGlcDAG is the first glucolipid
      along the glucolipid pathway, and a major (nonbilayer-prone) lipid in the single
      membrane of Acholeplasma laidlawii. MGlcDAG is further glucosylated to give the
      major diglucosyldiacylglycerol (DGlc-DAG). The bilayer fractions of these lipids
      are crucial for the metabolic maintenance of phase equilibria close to a
      potential bilayer-nonbilayer transition and a nearly constant spontaneous
      curvature. The glucolipid syntheses are also balanced against the
      phosphatidylglycerol pathway, competing for the common minor precursor
      phosphatidic acid, to retain a constant lipid surface charge density. The 1,2
      diacylglycerol 3-glucosyltransferase was purified to homogeneity from detergent
      solubilized A. laidlawii cells by three column chromatography methods (enrichment
      approximately 9000 x), and identified as a minor 40-kDa protein by using SDS
      polyacrylamide gel electrophoresis. In CHAPS detergent, mixed micelles, a
      cooperative dependence on anionic lipids for activity was confirmed. Dependence
      of the enzyme on UDP-glucose followed Michaelis-Menten kinetics while the other
      hydrophobic substrate dioleoylglycerol stimulated the enzyme by an activating,
      potentially cooperative mechanism. Physiological concentrations of the activator
      lipid dioleoyl-phosphatidylglycerol influenced the turnover number of the enzyme
      but not the interaction with UDP-glucose, as inferred from variable and constant
      values of the apparent Vmax and Km, respectively. Dipalmitoylglycerol was a
      better substrate than the oleoyl species, supporting earlier in vivo and crude
      enzyme data. The responses of the purified 1,2-diacylglycerol 3
      glucosyltransferase indicated that (i) the regulatory features of the MGlcDAG
      synthesis is held by the catalytic enzyme itself, and (ii) this strongly
      corroborates the "homeostasis" model for lipid bilayer properties in A. laidlawii
      proposed earlier.

PMID- 8995385
TI  - Chemotactic peptide N-formyl-met-leu-phe activation of p38 mitogen-activated
      protein kinase (MAPK) and MAPK-activated protein kinase-2 in human neutrophils.
AB  - Activation of polymorphonuclear leukocytes (PMN) by chemotactic peptides
      initiates a series of functional responses that serve to eliminate pathogens. The
      intermediate steps that link engagement of the chemoattractant receptor to the
      microbicidal responses involve protein kinases that have yet to be identified. In
      this study we detected in human PMN the presence of p38 mitogen-activated protein
      kinase (MAPK), which became rapidly tyrosine phosphorylated and activated in
      response to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine
      (fMLP). Pretreatment of PMN with wortmannin, a phosphatidylinositol 3-kinase
      inhibitor, or bis-indolylmaleimide, a protein kinase C antagonist, resulted in
      partial inhibition of p38 phosphorylation upon fMLP stimulation. Similarly,
      phosphorylation of p38 was only partially inhibited when the fMLP-induced
      cytosolic calcium transient was prevented. Stimulation of PMN by the
      chemoattractant also resulted in the rapid phosphorylation and activation of MAPK
      activated protein kinase-2 (MAPKAPK-2), which was completely inhibited by the
      specific p38 inhibitor, SB203580. The physical interaction of p38 with MAPKAPK-2
      was studied by coimmunoprecipitation. These two kinases were found to be
      associated in unstimulated PMN but dissociated upon activation of the cells by
      fMLP. Together these findings demonstrate the activation of p38 by chemotactic
      peptides in human PMN by a process involving phosphatidylinositol 3-kinase,
      protein kinase C, and calcium. p38, in turn, is an upstream activator of MAPKAPK
      2.

PMID- 8995386
TI  - On the role of DmpK, an auxiliary protein associated with multicomponent phenol
      hydroxylase from Pseudomonas sp. strain CF600.
AB  - DmpK from Pseudomonas sp. strain CF600 represents a group of proteins required by
      phenol-degrading bacteria that utilize a multicomponent iron-containing phenol
      hydroxylase. DmpK has been overexpressed in Escherichia coli and purified to
      homogeneity; it lacks redox cofactors and was found to strongly inhibit phenol
      hydroxylase in vitro. Chemical cross-linking experiments established that DmpK
      binds to the two largest subunits of the oxygenase component of the hydroxylase;
      this may interfere with binding of the hydroxylase activator protein, DmpM,
      causing inhibition. Since expression of DmpK normally appears to be much lower
      than that of the components of the oxygenase, inhibition may not occur in vivo.
      Hence, the interaction between DmpK and the oxygenase manifested in the
      inhibition and cross-linking results prompted construction of E. coli strains in
      which the oxygenase component was expressed in the presence and absence of a low
      molar ratio of DmpK. Active oxygenase was detected only when expressed in the
      presence of DmpK. Furthermore, inactive oxygenase could be activated in vitro by
      adding ferrous iron, in a process that was dependent on the presence of DmpK.
      These results indicate that DmpK plays a role in assembly of the active form of
      the oxygenase component of phenol hydroxylase.

PMID- 8995387
TI  - Determination of the specific substrate sequence motifs of protein kinase C
      isozymes.
AB  - Protein kinase C (PKC) family members play significant roles in a variety of
      intracellular signal transduction processes, but information about the substrate
      specificities of each PKC family member is quite limited. In this study, we have
      determined the optimal peptide substrate sequence for each of nine human PKC
      isozymes (alpha, betaI, betaII, gamma, delta, epsilon, eta, mu, and zeta) by
      using an oriented peptide library. All PKC isozymes preferentially phosphorylated
      peptides with hydrophobic amino acids at position +1 carboxyl-terminal of the
      phosphorylated Ser and basic residues at position -3. All isozymes, except PKC
      mu, selected peptides with basic amino acids at positions -6, -4, and -2. PKC
      alpha, -betaI, -betaII, -gamma, and -eta selected peptides with basic amino acid
      at positions +2, +3, and +4, but PKC delta, -epsilon, -zeta, and -mu preferred
      peptides with hydrophobic amino acid at these positions. At position -5, the
      selectivity was quite different among the various isozymes; PKC alpha, -gamma,
      and -delta selected peptides with Arg at this position while other PKC isozymes
      selected hydrophobic amino acids such as Phe, Leu, or Val. Interestingly, PKC mu
      showed extreme selectivity for peptides with Leu at this position. The predicted
      optimal sequences from position -3 to +2 for PKC alpha, -betaI, -betaII, -gamma, 
      delta, and -eta were very similar to the endogenous pseudosubstrate sequences of
      these PKC isozymes, indicating that these core regions may be important to the
      binding of corresponding substrate peptides. Synthetic peptides based on the
      predicted optimal sequences for PKC alpha, -betaI,-delta, -zeta, and -mu were
      prepared and used for the determination of Km and Vmax for these isozymes. As
      judged by Vmax/Km values, these peptides were in general better substrates of the
      corresponding isozymes than those of the other PKC isozymes, supporting the idea
      that individual PKC isozymes have distinct optimal substrates. The structural
      basis for the selectivity of PKC isozymes is discussed based on residues
      predicted to form the catalytic cleft.

PMID- 8995388
TI  - Isolation and characterization of mycophenolic acid-resistant mutants of inosine
      5'-monophosphate dehydrogenase.
AB  - Mycophenolic acid (MPA) is a potent and specific inhibitor of mammalian inosine
      monophosphate dehydrogenases (IMPDH); most microbial IMPDHs are not sensitive to
      MPA. MPA-resistant mutants of human IMPDH type II were isolated in order to
      identify the structural features that determine the species selectivity of MPA.
      Three mutant IMPDHs were identified with decreased affinity for MPA The mutation
      of Gln277 --> Arg causes a 9-fold increase in the Ki of MPA, a 5-6-fold increase
      in the Km values for IMP and NAD, and a 3-fold decrease in kcat relative to wild
      type. The mutation of Ala462 --> Thr causes a 3-fold increase in the Ki for MPA,
      a 2.5-fold increase in the Km for NAD, and a 1.5-fold increase in kcat. The
      combination of these two mutations does not increase the Ki for MPA, but does
      increase the Km for NAD 3-fold relative to Q277R and restores kcat to wild type
      levels. Q277R/A462T is the first human IMPDH mutant with increased Ki for MPA and
      wild type activity. The third mutant IMPDH contains two mutations, Phe465 --> Ser
      and Asp470 --> Gly. Ki for MPA is increased 3-fold in this mutant enzyme, and Km
      for IMP is also increased 3-fold, while the Km for NAD and kcat are unchanged.
      Thus increases in the Ki for MPA do not correlate with changes in Km for either
      IMP or NAD, nor to changes in kcat. All four of these mutations are in regions of
      the IMPDH that differ in mammalian and microbial enzymes, and thus can be
      structural determinants of MPA selectivity.

PMID- 8995389
TI  - Maxadilan, the vasodilator from sand flies, is a specific pituitary adenylate
      cyclase activating peptide type I receptor agonist.
AB  - Maxadilan is a potent vasodilator peptide isolated from salivary gland lysates of
      the sand fly Lutzomyia longipalpis, a vector of leishmaniasis. The peptide aids
      the fly in obtaining blood from the skin of its vertebrate hosts but the
      mammalian receptor through which this insect ligand acts was unknown. We
      demonstrate that maxadilan is an agonist of the type I receptor for pituitary
      adenylate cyclase activating peptide, a neuropeptide with vascular activity. This
      surprising observation is a unique example of convergent evolution from a
      functional standpoint as these two peptides do not share significant sequence
      homology.

PMID- 8995391
TI  - Characterization of inducible nitric-oxide synthase by cytochrome P-450
      substrates and inhibitors. Inhibition by chlorzoxazone.
AB  - Nitric-oxide synthases (NOS, EC 1.14.13.39) are heme-containing enzymes that
      catalyze the formation of nitric oxide from L-Arg. General cytochrome P-450
      inhibitors and cytochrome P-450 isoform-selective substrates and inhibitors were
      used to characterize the activity of recombinant human inducible NOS (iNOS).
      Classical cytochrome P-450 ligands such as the mechanism-based inactivator 1
      aminobenzotriazole did not inhibit iNOS. Of a panel of 30 human cytochrome P-450
      isoform-selective substrates and inhibitors, only chlorzoxazone, a cytochrome P
      450 2E1 (CYP2E1) substrate, showed any significant inhibition of iNOS activity.
      Chlorzoxazone was not a substrate for iNOS but was a potent competitive inhibitor
      with respect to L-Arg with Ki = 3.3+/-0.7 microM. The binding of chlorzoxazone to
      iNOS and human and rat liver microsomal cytochrome P-450 induced a high spin,
      type I spectra, which was reversed by imidazole. Although the binding of
      chlorzoxazone to iNOS and its inhibition of iNOS activity suggest some similarity
      between iNOS and CYP2E1 activity, other CYP2E1 substrates and inhibitors
      including zoxazolamine were not inhibitors of iNOS. Overall, iNOS activity is
      distinctly different from the major cytochrome P-450 enzymes in human liver
      microsomes.

PMID- 8995390
TI  - Tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes is
      accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression
      without a loss of insulin receptor-mediated signal transduction.
AB  - A number of studies have demonstrated that tumor necrosis factor-alpha (TNF
      alpha) is associated with profound insulin resistance in adipocytes and may also
      play a critical role in the insulin resistance of obesity and non-insulin
      dependent diabetes mellitus. Reports on the mechanism of TNF-alpha action have
      been somewhat contradictory. GLUT4 down-regulation has been implicated as a
      possible cause of insulin resistance as has been the reduced kinase function of
      the insulin receptor. Here we examine the effects of tumor necrosis factor on the
      protein components thought to be involved in insulin-stimulated glucose transport
      in adipocytes, namely the insulin receptor, its major substrate IRS-1, and the
      insulin responsive glucose transporter GLUT4. Prolonged exposure (72-96 h) of 3T3
      L1 adipocytes to TNF-alpha causes a substantial reduction (>80%) in IRS-1 and
      GLUT4 mRNA and protein as well as a lesser reduction (>50%) in the amount of the
      insulin receptor. Nevertheless, the remaining proteins appear to be biochemically
      indistinguishable from those in untreated adipocytes. Both the insulin receptor
      and IRS-1 are tyrosine-phosphorylated to the same extent in response to acute
      insulin stimulation following cellular TNF-alpha exposure. Furthermore, the
      ability of the insulin receptor to phosphorylate exogenous substrate in the test
      tube is also normal following its isolation from TNF-alpha-treated cells. These
      results are confirmed by the reduced but obvious level of insulin-dependent
      glucose transport and GLUT4 translocation observed in TNF-alpha-treated
      adipocytes. We conclude that the insulin resistance of glucose transport in 3T3
      L1 adipocytes exposed to TNF-alpha for 72-96 h results from a reduced amount in
      requisite proteins involved in insulin action. These results are consistent with
      earlier studies indicating that TNF-alpha reduces the transcriptional activity of
      the GLUT4 gene in murine adipocytes, and reduced mRNA transcription of a number
      of relevant genes may be the general mechanism by which TNF-alpha causes insulin
      resistance in adipocytes.

PMID- 8995392
TI  - Identification and characterization of a nuclease specific for the 3' end of the
      U6 small nuclear RNA.
AB  - The U6 small nuclear RNA is post-transcriptionally processed by the addition and
      removal of nontemplate uridylates (Us) at its 3' end prior to incorporation into
      the U4 x U6 small nuclear ribonucleoprotein complex. An enzyme responsible for
      removing Us from the U6 3' end has not been previously identified. Here we
      biochemically isolate and characterize an exonuclease activity from HeLa cells
      that removes template and nontemplate 3'-nucleotides specifically from U6 RNA. We
      also report the isolation of an inhibitor of this U6 nuclease. U6 nuclease
      rapidly removes the four terminal 3' Us found in the human U6 coding sequence in
      a magnesium-dependent manner. Mutagenesis studies on the U6 RNA define regions
      essential for processing. U6 nuclease recognizes specific sequences on both
      strands near the base of the major intramolecular stem loop of the U6 RNA. The
      preprocessed 3' Us form part of the base of the stem loop, but neither specific
      sequences nor secondary structure at the four terminal nucleotides are required
      to achieve processing.

PMID- 8995393
TI  - Voltage-dependent porin-like ion channels in the archaeon Haloferax volcanii.
AB  - Membrane vesicles isolated from the cell envelope of the archaebacterium
      Haloferax volcanii were either reconstituted in giant liposomes and examined by
      the patch-clamp technique or were fused into planar lipid bilayers. In addition,
      cell envelope proteins were solubilized by detergent and reconstituted in
      azolectin liposomes, which were then fused into planar lipid bilayers.
      Independently of the technique used the predominant channel activity encountered
      exhibited the following characteristics. Channels were open at all voltages in
      the range approximately -120 to +120 mV and exhibited frequent fast transitions
      to closed levels of different amplitudes. At voltages greater than 120 mV the
      channels tended to close in a manner characterized by large, slow transitions of
      variable amplitudes. The tendency to close at high membrane potentials was much
      stronger at one polarity. The channel gating pattern was complex exhibiting a
      range of subconductances of 10-300 picosiemens in symmetric 100 mM KCl. These
      electrophysiological characteristics are comparable with those of bacterial and
      mitochondrial porins, suggesting that the archaeal channels may belong to the
      general class of porin channels. Some channels showed preference for K+, whereas
      the others preferred Cl-, suggesting the existence of at least two types of porin
      like channels in H. volcanii.

PMID- 8995394
TI  - Autotaxin is an exoenzyme possessing 5'-nucleotide phosphodiesterase/ATP
      pyrophosphatase and ATPase activities.
AB  - Autotaxin (ATX) is an extracellular enzyme and an autocrine motility factor that
      stimulates pertussis toxin-sensitive chemotaxis in human melanoma cells at
      picomolar to nanomolar concentrations. This 125-kDa glycoprotein contains a
      peptide sequence identified as the catalytic site in type I alkaline
      phosphodiesterases (PDEs), and it possesses 5'-nucleotide PDE (EC 3.1.4.1)
      activity (Stracke, M. L., Krutzsch, H. C., Unsworth, E. J., Arestad, A., Cioce,
      V., Schiffmann, E., and Liotta, L. (1992) J. Biol. Chem. 267, 2524-2529; Murata,
      J., Lee, H. Y., Clair, T., Krutsch, H. C., Arestad, A. A., Sobel, M. E., Liotta,
      L. A., and Stracke, M. L. (1994) J. Biol. Chem. 269, 30479-30484). ATX binds ATP
      and is phosphorylated only on threonine. Thr210 at the PDE active site of ATX is
      required for phosphorylation, 5'-nucleotide PDE, and motility-stimulating
      activities (Lee, H. Y., Clair, T., Mulvaney, P. T., Woodhouse, E. C.,
      Aznavoorian, S., Liotta, L. A., and Stracke, M. L. (1996) J. Biol. Chem. 271,
      24408-24412). In this article we report that the phosphorylation of ATX is a
      transient event, being stable at 0 degrees C but unstable at 37 degrees C, and
      that ATX has adenosine-5'-triphosphatase (ATPase; EC 3.6.1.3) and ATP
      pyrophosphatase (EC 3.6.1.8) activities. Thus ATX catalyzes the hydrolysis of the
      phosphodiester bond on either side of the beta-phosphate of ATP. ATX also
      catalyzes the hydrolysis of GTP to GDP and GMP, of either AMP or PPi to Pi, and
      the hydrolysis of NAD to AMP, and each of these substrates can serve as a
      phosphate donor in the phosphorylation of ATX. ATX possesses no detectable
      protein kinase activity toward histone, myelin basic protein, or casein. These
      results lead to the proposal that ATX is capable of at least two alternative
      reaction mechanisms, threonine (T-type) ATPase and 5'-nucleotide PDE/ATP
      pyrophosphatase, with a common site (Thr210) for the formation of covalently
      bound reaction intermediates threonine phosphate and threonine adenylate,
      respectively.

PMID- 8995395
TI  - Molecular cloning, genomic organization, and developmental regulation of a novel
      receptor from Drosophila melanogaster structurally related to members of the
      thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing
      hormone/choriogonadotropin receptor family from mammals.
AB  - Using oligonucleotide probes derived from consensus sequences for glycoprotein
      hormone receptors, we have cloned an 831-amino acid residue-long receptor from
      Drosophila melanogaster that shows a striking structural homology with members of
      the glycoprotein hormone (thyroid-stimulating hormone (TSH); follicle-stimulating
      hormone (FSH); luteinizing hormone/choriogonadotropin (LH/CG)) receptor family
      from mammals. This homology includes a very large, extracellular N terminus (20%
      sequence identity with rat TSH, 19% with rat FSH, and 20% with the rat LH/CG
      receptor) and a seven-transmembrane region (53% sequence identity with rat TSH,
      50% with rat FSH, and 52% with the rat LH/CG receptor). The Drosophila receptor
      gene is >7.5 kilobase pairs long and contains 17 exons and 16 introns. Seven
      intron positions coincide with introns in the mammalian glycoprotein hormone
      receptor genes and have the same intron phasing. This indicates that the
      Drosophila receptor is evolutionarily related to the mammalian receptors. The
      Drosophila receptor gene is located at position 90C on the right arm of the third
      chromosome. The receptor is strongly expressed starting 8-16 h after oviposition,
      and the expression stays high until after pupation. Adult male flies express high
      levels of receptor mRNA, but female flies express about 6 times less. The
      expression pattern in embryos and larvae suggests that the receptor is involved
      in insect development. This is the first report on the molecular cloning of a
      glycoprotein hormone receptor family member from insects.

PMID- 8995396
TI  - Determination of key structural requirements of a K+ channel pore.
AB  - Among the highly conserved sites in K+ channel pores, the tyrosine-glycine
      sequence is believed to play an important role in selectivity. Here we describe a
      novel approach in which comprehensive mutagenesis of the YG sites of the voltage
      gated K+ channel, Kat1, is combined with phenotypic screening in Saccharomyces
      cerevisiae and electrophysiological analysis in Xenopus oocytes to determine the
      roles of these sites in K+ selectivity. We show that structural constraints
      necessitate a tyrosine or phenylalanine at the first position to confer full K+
      selectivity. Substitution to arginine creates a channel titratable by external
      pH, suggesting that the side group at this position may line the channel pore.
      Permeation is abolished by any increase in bulk at the adjacent glycine position
      unless accompanied by a compensatory mutation at the tyrosine site. These results
      suggest a model in which the selectivity filter of the K+ channel requires an
      aromatic residue paired with glycine within the pore loop in order to maintain
      maximal K+ selectivity.

PMID- 8995397
TI  - TAO1, a representative of the molybdenum cofactor containing hydroxylases from
      tomato.
AB  - Aldehyde oxidase and xanthine dehydrogenase are a group of ubiquitous
      hydroxylases, containing a molybdenum cofactor (MoCo) and two iron-sulfur groups.
      Plant aldehyde oxidase and xanthine dehydrogenase activities are involved in
      nitrogen metabolism and hormone biosynthesis, and their corresponding genes have
      not yet been isolated. Here we describe a new gene from tomato, which shows the
      characteristics of a MoCo containing hydroxylase. It shares sequence homology
      with xanthine dehydrogenases and aldehyde oxidases from various organisms, and
      similarly contains binding sites for two iron-sulfur centers and a molybdenum
      binding region. However, it does not contain the xanthine dehydrogenase conserved
      sequences thought to be involved in NAD binding and in substrate specificity, and
      is likely to encode an aldehyde oxidase-type activity. This gene was designated
      tomato aldehyde oxidase 1 (TAO1). TAO1 belongs to a multigene family, whose
      members are shown to map to clusters on chromosomes 1 and 11. MoCo hydroxylase
      activity is shown to be recognized by antibodies raised against recombinant TAO1
      polypeptides. Immunoblots reveal that TAO1 cross-reacting material is
      ubiquitously expressed in various organisms, and in plants it is mostly abundant
      in fruits and rapidly dividing tissues.

PMID- 8995398
TI  - Role of multidrug resistance P-glycoproteins in cholesterol esterification.
AB  - Cholesterol esterification, catalyzed by acyl-CoA:cholesterol acyltransferase
      (ACAT), plays a central role in cellular cholesterol homeostasis and in
      physiologic processes that lead to coronary heart disease. Although ACAT resides
      in the endoplasmic reticulum (ER), the cholesterol substrate for esterification
      originates in the plasma membrane and must be transported to the ER for
      esterification. Progesterone inhibits esterification, possibly by blocking the
      transport of cholesterol to the ER. Recent studies suggest that progesterone acts
      by inhibiting the activity of one or more of the multidrug-resistant (MDR) P
      glycoproteins. In the current manuscript, we demonstrate that progesterone's
      ability to inhibit esterification is not mediated through the progesterone
      receptor. We evaluate a series of steroid hormones and find a strong correlation
      between a steroid hormone's hydrophobicity and its ability to inhibit both
      cholesterol esterification and MDR-catalyzed drug efflux. We also find that
      cholesterol esterification is inhibited by nonsteroidal MDR inhibitors, and that
      this inhibition specifically affects the esterification of cholesterol derived
      from the plasma membrane. MDR inhibitors also inhibit cholesterol esterification
      in a wide range of cultured human cell lines. These observations suggest that MDR
      activity normally functions in a general process of intracellular cholesterol
      transport.

PMID- 8995399
TI  - Molecular characterization of specific interactions between SHP-2 phosphatase and
      JAK tyrosine kinases.
AB  - Interactions between SHP-2 phosphotyrosine phosphatase and JAK tyrosine kinases
      have recently been implicated in cytokine signal transduction. However, the
      molecular basis of these interactions is not well understood. In this study, we
      demonstrate that SHP-2 is tyrosine-phosphorylated by and associated with JAK1 and
      JAK2 but not JAK3 in COS-1 cell cotransfection experiments. SHP-2 phosphatase
      activity appears not to be required for JAK and SHP-2 interactions because SHP-2
      with a mutation at amino acid 463 from Cys to Ser, which renders SHP-2 inactive,
      can still bind JAKs. We further demonstrate that SHP-2 SH2 domains (amino acids 1
      209) are not essential for the association of JAKs with SHP-2, and the region
      between amino acids 232 and 272 in SHP-2 is important for the interactions.
      Furthermore, tyrosine residues 304 and 327 in SHP-2 are phosphorylated by JAKs,
      and phosphorylated SHP-2 can associate with the downstream adapter protein Grb2.
      Finally, deletion of the N terminus but not the kinase-like domain of JAK2
      abolishes the association of JAK2 with SHP-2. Taken together, these studies
      identified novel sequences for SHP-2 and JAK interactions that suggest unique
      signaling mechanisms mediated by these two molecules.

PMID- 8995400
TI  - Organization and differential expression of the human monocyte chemoattractant
      protein 1 receptor gene. Evidence for the role of the carboxyl-terminal tail in
      receptor trafficking.
AB  - Two forms of the monocyte chemoattractant protein-1 receptors (the type A
      monocyte chemoattractant protein 1 (MCP-1) receptor CCR-2A and the type B MCP-1
      receptor (CCR-2B) have been recently cloned and found to differ only in their
      terminal carboxyl tails. Here, we report that the two isoforms are alternatively
      spliced variants of a single MCP-1 receptor gene. Sequencing of the gene revealed
      that the 47-amino acid carboxyl tail of CCR2B was located in the same exon as the
      seven transmembrane domains of the receptor, and the 61-amino acid tail of CCR2A
      was in a downstream exon. Examination of freshly isolated human monocytes by
      reverse transcriptase-polymerase chain reaction revealed that CCR2B was the
      predominant isoform and that message levels of both CCR2A and CCR2B decreased as
      the monocytes differentiated into macrophages. In stably transfected cell lines,
      CCR2B trafficked well to the cell surface, but CCR2A was found predominantly in
      the cytoplasm. Equilibrium binding studies revealed that those CCR2A receptors
      that successfully trafficked to the cell surface bound MCP-1 with high affinity
      (Kd = 310 pM), similar to CCR2B. In signaling studies, both CCR2A and CCR2B
      mediated agonist-dependent calcium mobilization, as well as inhibition of
      adenylyl cyclase. Creation of chimeras between CCR2A and the human thrombin
      receptor revealed that the cytoplasmic retention of CCR2A was due to its terminal
      carboxyl tail. Progressive truncation of the carboxyl tail indicated that a
      cytoplasmic retention signal(s) was located between residues 316 and 349. These
      data indicate that the alternatively spliced form of the human MCP-1 receptor
      (CCR2A) binds MCP-1 with high affinity and is a functional receptor and that
      expression at the cell surface is controlled by amino acid sequences located in
      the terminal carboxyl tail.

PMID- 8995401
TI  - The phosphorylation state of translation initiation factors is regulated
      developmentally and following heat shock in wheat.
AB  - Several translation initiation factors in mammals and yeast are regulated by
      phosphorylation. The phosphorylation state of these factors is subject to
      alteration during development, environmental stress (heat shock, starvation, or
      heme deprivation), or viral infection. The phosphorylation state and the effect
      of changes in phosphorylation of the translation initiation factors of higher
      plants have not been previously investigated. We have determined the isoelectric
      states for the wheat translation initiation factors eIF-4A, eIF-4B, eIF-4F, eIF
      iso4F, and eIF-2 and the poly(A)-binding protein in the seed, during germination,
      and following heat shock of wheat seedlings using two-dimensional gel
      electrophoresis and Western analysis. We found that the developmentally induced
      changes in isoelectric state observed during germination or the stress-induced
      changes were consistent with changes in phosphorylation. Treatment of the
      phosphorylated forms of the factors with phosphatases confirmed that the nature
      of the modification was due to phosphorylation. The isoelectric states of eIF-4B,
      eIF-4F (eIF-4E, p26), eIF-iso4F (eIF-iso4E, p28), and eIF-2alpha (p42) were
      altered during germination, suggesting that phosphorylation of these factors is
      developmentally regulated and correlates with the resumption of protein synthesis
      that occurs during germination. The phosphorylation of eIF-2beta (p38) or poly(A)
      binding protein did not change either during germination or following a thermal
      stress. Only the phosphorylation state of two factors, eIF-4A and eIF-4B, changed
      following a heat shock, suggesting that plants may differ significantly from
      animals in the way in which their translational machinery is modified in response
      to a thermal stress.

PMID- 8995402
TI  - Sequence requirements for regulated RNA splicing of the human fibroblast growth
      factor receptor-1 alpha exon.
AB  - Progression of astrocytes from a benign to a malignant phenotype is accompanied
      by a change in the RNA processing of the fibroblast growth factor receptor 1
      (FGFR-1) gene. The level of a high affinity form of the FGFR-1 is dramatically
      elevated as a result of alpha-exon skipping during RNA splicing. In this paper we
      have been able to duplicate this tumor-specific RNA processing pathway by
      transfection of a chimeric minigene containing a 4-kilobase fragment of the human
      FGFR-1 gene (including the alpha-exon) into a variety of cell lines. In a
      transfected human astrocytoma cell line, alpha-exon skipping was consistently
      observed for RNA transcripts derived from both the chimeric minigene and
      endogenous gene expression. This exon skipping phenotype was dependent on the
      size of the flanking intron as deletions which reduced the introns to less than
      approximately 350 base pairs resulted in enhanced alpha-exon inclusion. Increased
      exon inclusion was not sequence-specific as exon skipping could be restored with
      insertion of nonspecific sequence. Cell-specific exon recognition was maintained
      with a 375-nucleotide sequence inclusive and flanking the alpha-exon, provided
      that intron size was maintained. These results identify the minimal cis
      regulatory sequence requirements for exclusion of FGFR-1 alpha-exon in
      astrocytomas.

PMID- 8995403
TI  - DNA intersegment transfer, how steroid receptors search for a target site.
AB  - The mammalian nucleus contains 6 billion base pairs of DNA, encoding about
      100,000 genes, yet in a given cell steroid hormones induce only a handful of
      genes. The logistical difficulties faced by steroid receptors or other
      transcription factors of sorting through this much genetic information is further
      increased by the density of nuclear DNA (approximately 10-50 mg/ml). Standard
      models propose that steroid receptors find target elements by repeated cycles of
      dissociation and reassociation until a high affinity site is found (cycling
      model) and/or by conducting a one-dimensional search along the DNA (sliding
      model). A third model proposes that steroid receptors search for target sites in
      the genome by DNA intersegment transfer. In this model, receptor dimers bind
      nonspecific DNA sequences and search for a target site by binding a second strand
      of DNA before dissociating from the first, in effect moving through the genome
      like Tarzan swinging from vine to vine. This model has the advantage that a high
      concentration of DNA favors, rather than hinders, the search. The intersegment
      transfer model predicts, in contrast to the cycling and sliding models, that the
      dissociation rate of receptor from DNA is highly dependent on DNA concentration.
      We have employed the purified DNA binding domain fragment from the rat
      glucocorticoid receptor to perform equilibrium and kinetic studies of the DNA
      dependence of receptor-DNA dissociation. We find receptor dissociation from DNA
      to be highly dependent on the concentration of DNA in solution, in agreement with
      the intersegment transfer model. We also find that this interaction is primarily
      electrostatic, because DNA-like polyanion chains (e.g. heparin and polyglutamate)
      can mediate the transfer. These studies provide evidence that direct DNA transfer
      aids the target site search conducted by steroid receptors in their role as
      inducible transcription factors.

PMID- 8995404
TI  - Cell-permeable ceramides prevent the activation of phospholipase D by ADP
      ribosylation factor and RhoA.
AB  - The mechanism of inhibition of phospholipase D (PLD) by ceramides was determined
      using granulocytes differentiated from human promyelocytic leukemic (HL-60)
      cells. In a cell-free system, hydrolysis of phosphatidylcholine by membrane-bound
      PLD depended upon phosphatidylinositol 4,5-bisphosphate, guanosine 5'-3-O
      (thio)triphosphate) (GTPgammaS), and cytosolic factors including ADP-ribosylating
      factor (ARF) and RhoA. C2-(N-acetyl-), C8- (N-octanoyl-), and long-chain
      ceramides, but not dihydro-C2-ceramide, inhibited PLD activity. Apyrase or
      okadaic acid did not modify the inhibition of PLD by ceramides, indicating that
      the effect in the cell-free system was unlikely to be dependent upon a ceramide
      stimulated kinase or phosphoprotein phosphatases. C2- and C8-ceramides prevented
      the GTPgammaS-induced translocation of ARF1 and RhoA from the cytosol to the
      membrane fraction. In whole cells, C2-ceramide, but not dihydro-C2-ceramide,
      inhibited the stimulation of PLD by N-formylmethionylleucylphenylalanine and
      decreased the amounts of ARF1, RhoA, CDC42, Rab4, and protein kinase C-alpha and 
      beta1 that were associated with the membrane fraction, but did not alter the
      distribution of protein kinase C-epsilon and -zeta. It is concluded that one
      mechanism by which ceramides prevent the activation of PLD is inhibition of the
      translocation to membranes of G-proteins and protein kinase C isoforms that are
      required for PLD activity.

PMID- 8995405
TI  - Complementary DNA cloning and sequencing of the chicken muscle ecto-ATPase.
      Homology with the lymphoid cell activation antigen CD39.
AB  - The ecto-ATPase from chicken gizzard (smooth muscle) was solubilized, and the 66
      kDa cell membrane ecto-ATPase protein was purified. The protein was then
      subjected to both enzymatic and chemical cleavage, and the resultant peptides
      were purified by reverse phase high pressure liquid chromatography and sequenced.
      Several of these internal peptide sequences were used to design oligonucleotides
      to screen a chicken muscle library to identify the cDNA encoding the ecto-ATPase.
      Two overlapping partial clones were sequenced, yielding the complete coding
      region and a long 3'-untranslated sequence. The deduced amino acid sequence is in
      agreement with the N-terminal and peptide sequences obtained from the purified
      protein. The chicken muscle ecto-ATPase is a slightly basic (predicted pI = 7.93)
      494-amino acid protein (54.4 kDa), containing a single transmembrane domain at
      each end of the protein. The majority of the protein is predicted to be
      extracellular, making it a Type Ia plasma membrane protein. There are four
      putative N-glycosylation sites, a single potential cAMP/cGMP-dependent protein
      kinase phosphorylation site, as well as a single putative tyrosine kinase
      phosphorylation site. Analysis of the sequence using the BLAST programs
      demonstrated homology with other ecto-ATPases and ecto-apyrases, including those
      from the parasitic protozoan Toxoplasma gondii, potato tubers, and garden pea, as
      well as a guanosine diphosphohydrolase from yeast. However, the most striking
      homology observed was to the human and mouse lymphoid cell activation antigen 39
      (CD39), a molecule now known to have apyrase activity. The chicken ecto-ATPase
      showed considerable amino acid sequence homology with CD39 over the entire length
      of the sequence, excluding about 30-40 amino acids at the extreme ends of the
      protein (which include the two membrane-spanning helices). The sequence homology
      between the gizzard ecto-ATPase and CD39 was confirmed by Western blots
      demonstrating immunocross-reactivity between mono- and polyclonal antibodies
      raised against the chicken ecto-ATPase and two commercially available monoclonal
      antibodies against the human CD39 protein. The results suggest that the muscle
      ecto-ATPase may be involved in cell adhesion, since the highly homologous CD39
      protein is involved in homotypic adhesion of activated B lymphocytes.

PMID- 8995406
TI  - Characterization and functional analysis of 12 naturally occurring reactive site
      variants of serpin-1 from Manduca sexta.
AB  - Serpin gene-1 from the tobacco hornworm, Manduca sexta, encodes, through
      alternative exon usage, 12 reactive site variants (Jiang, H., Wang, Y. and
      Kanost, M. R., (1994) J. Biol. Chem. 269, 55-58; Jiang, H., Wang, Y., Huang, Y.,
      Mulnix, A. B., Kadel, J., Cole, K., and Kanost, M. R. (1996) J. Biol. Chem. 271,
      28017-28023). These 43-kDa proteins differ from each other only in their COOH
      terminal 39-46 residues, which include the reactive site. To test the hypothesis
      that these proteins are proteinase inhibitors of diverse selectivities and to
      begin to elucidate their physiological functions, we expressed the 12 serpin-1
      variants in Escherichia coli. Seven of the variants inhibited mammalian serine
      proteinases, with association rate constants comparable with those of human
      serpins. Serpin-1A, with a P1 Arg residue, inhibited both trypsin and plasmin.
      Serpin-1B (P1 Ala) and serpin-1F (P1 Val) inhibited porcine pancreatic elastase
      and human neutrophil elastase. Serpin-1H, -1K, and -1Z, all with a Tyr residue at
      the P1 position, inhibited chymotrypsin and cathepsin G. Serpin-1I (P1 Leu)
      inhibited both elastase and chymotrypsin. Nine of the serpin variants were active
      as inhibitors of microbial serine proteinases, including subtilisin Carlsberg,
      proteinase K, and two proteinases secreted by an entomopathogenic fungus,
      Metarhizium anisopliae. In addition, one of the serpin variants, serpin-1J,
      strongly inhibited activation of M. sexta hemolymph phenoloxidase, a pathway
      involving a serine proteinase cascade. This pathway is a component of the
      defensive response of insects to microbial infection. These results suggest that
      the products of M. sexta serpin gene-1 may be important in regulating both
      exogenous and endogenous serine proteinases in hemolymph.

PMID- 8995407
TI  - Ligand perturbation effects on a pseudotetrahedral Co(II)(His)3-ligand site. A
      magnetic circular dichroism study of the Co(II)-substituted insulin hexamer.
AB  - Magnetic circular dichroism (MCD) spectra of a series of adducts formed by the
      Co(II)-substituted R-state insulin hexamer are reported. The His-B10 residues in
      this hexamer form tris imidazole chelates in which pseudotetrahedral Co(II)
      centers are completed by an exogenous fourth ligand. This study investigates how
      the MCD signatures of the Co(II) center in this unit are influenced by the
      chemical and steric characteristics of the fourth ligand. The spectra obtained
      for the adducts formed with halides, pseudohalides, trichloroacetate, nitrate,
      imidazole, and 1-methylimidazole appear to be representative of near tetrahedral
      Co(II) geometries. With bulkier aromatic ligands, more structured spectra
      indicative of highly distorted Co(II) geometries are obtained. The MCD spectrum
      of the phenolate adduct is very similar to those of Co(II)-carbonic anhydrase
      (alkaline form) and Co(II)-beta-lactamase. The MCD spectrum of the Co(II)-R6-CN-
      adduct is very similar to the CN- adduct of Co(II)-carbonic anhydrase. The close
      similarity of the Co(II)-R6-pentafluorophenolate and Co(II)-R6-phenolate spectra
      demonstrates that the Co(II)-carbonic anhydrase-like spectral profile is
      preserved despite a substantial perturbation in the electron withdrawing nature
      of the coordinated phenolate oxygen atom. We conclude that this type of spectrum
      must arise from a specific Co(II) coordination geometry common to each of the
      Co(II) sites in the Co(II)-R6-phenolate, Co(II)-R6-pentafluorophenolate, Co(II)
      beta-lactamase, and the alkaline Co(II)-carbonic anhydrase species. These
      spectroscopic results are consistent with a trigonally distorted tetrahedral
      Co(II) geometry (C3v), an interpretation supported by the pseudotetrahedral
      Zn(II)(His)3(phenolate) center identified in a Zn(II)-R6 crystal structure
      (Smith, G. D., and Dodson, G. G. (1992) Biopolymers 32, 441-445).

PMID- 8995408
TI  - Activation of transducin by a Xenopus short wavelength visual pigment.
AB  - Phototransduction in cones differs significantly from that in rods in
      sensitivity, kinetics, and recovery following exposure to light. The contribution
      that the visual pigment makes in determining the cone response was investigated
      biochemically by expressing a Xenopus violet cone opsin (VCOP) cDNA in COS1 cells
      and assaying the light-dependent activation of transducin. Light-exposed VCOP
      stimulated [35S]guanosine 5'-(gamma-thio)triphosphate nucleotide exchange on
      bovine rod transducin in a time-dependent manner with a half-time for activation
      of 0.75 min, similar to that of bovine rhodopsin. In exhaustive binding assays,
      VCOP and rhodopsin activity showed similar concentration dependence with half
      maximal activation occurring at 0.02 mol of pigment/mol of transducin. Although
      VCOP was able to activate as many as 12 transducins per photoisomerization,
      rhodopsin catalyzed significantly more. When assays were performed with lambda >
      420 nm illumination, VCOP exhibited rapid regeneration and high affinity for the
      photoregenerated 11-cis-retinal. Recycling of the chromophore and reactivation of
      the pigment resulted in multiple activations of transducin, whereas a maximum of
      1 transducin per VCOP was activated under brief illumination. The decay of the
      active species formed following photobleaching was complete in <5 min,
      approximately 10-fold faster than that of rhodopsin. In vitro, VCOP activated rod
      transducin with kinetics and affinity similar to those of rhodopsin, but the
      active conformation decayed more rapidly and the apoprotein regenerated more
      efficiently with VCOP than with rhodopsin. These properties of the violet pigment
      may account for much of the difference in response kinetics between rods and
      cones.

PMID- 8995409
TI  - Conservation and diversity of eukaryotic translation initiation factor eIF3.
AB  - The largest of the mammalian translation initiation factors, eIF3, consists of at
      least eight subunits ranging in mass from 35 to 170 kDa. eIF3 binds to the 40 S
      ribosome in an early step of translation initiation and promotes the binding of
      methionyl-tRNAi and mRNA. We report the cloning and characterization of human
      cDNAs encoding two of its subunits, p110 and p36. It was found that the second
      slowest band during polyacrylamide gel electrophresis of eIF3 subunits in sodium
      dodecyl sulfate contains two proteins: p110 and p116. Analysis of the cloned cDNA
      encoding p110 indicates that its amino acid sequence is 31% identical to that of
      the yeast protein, Nip1. The p116 cDNA was cloned and characterized as a human
      homolog of yeast Prt1, as described elsewhere (Methot, N., Rom, E., Olsen, H.,
      and Sonenberg, N. (1997) J. Biol. Chem. 272, 1110-1116). p36 is a WD40 repeat
      protein, which is 46% identical to the p39 subunit of yeast eIF3 and is identical
      to TRIP-1, a phosphorylation substrate of the TGF-beta type II receptor. The
      p116, p110, and p36 subunits localize on 40 S ribosomes in cells active in
      translation and co-immunoprecipitate with affinity-purified antibodies against
      the p170 subunit, showing that these proteins are integral components of eIF3.
      Although p36 and p116 have homologous protein subunits in yeast eIF3, the p110
      homolog, Nip1, is not detected in yeast eIF3 preparations. The results indicate
      both conservation and diversity in eIF3 between yeast and humans.

PMID- 8995410
TI  - The human homologue of the yeast Prt1 protein is an integral part of the
      eukaryotic initiation factor 3 complex and interacts with p170.
AB  - Eukaryotic initiation factor 3 (eIF3) is a large multisubunit complex that
      stabilizes the ternary complex, eIF2 x GTP x tRNA(Met)i and promotes mRNA binding
      to the 40 S ribosomal subunit. eIF3 also functions as a ribosome subunit anti
      association factor. The molecular mechanisms by which eIF3 exerts these functions
      are poorly understood. We describe here the cloning of the cDNA encoding the
      human homologue of the yeast eIF3 subunit Prt1. The human PRT1 cDNA encodes a
      protein of predicted molecular mass of 98.9 kDa that migrates at 116 kDa on SDS
      polyacrylamide gels. Human and yeast Prt1 share 31% identity and 50% similarity
      at the amino acid level. The homology is distributed throughout the entire
      protein, except for the amino terminus, and is particularly high in the central
      portion of the protein, which contains a putative RNA recognition motif. hPrt1 is
      recognized by an antibody raised against eIF3, and an affinity-purified antibody
      to recombinant hPrt1 recognizes a protein migrating at 116 kDa in a purified eIF3
      preparation. Far Western analysis shows that hPrt1 interacts directly with the
      p170 subunit of eIF3. Mapping studies identify the RNA recognition motif as the
      region required for association with p170. Taken together, these experiments
      demonstrate that hPrt1 is a component of eIF3. Our data, combined with those of
      Hershey and co-workers, suggest that mammalian eIF3 is composed of at least 10
      subunits: p170, p116 (hPrt1), p110, p66, p48, p47, p44, p40, p36, and p35.

PMID- 8995411
TI  - Loss of binding and entry of liposome-DNA complexes decreases transfection
      efficiency in differentiated airway epithelial cells.
AB  - The target cells for gene therapy of cystic fibrosis lung disease are the well
      differentiated cells that line airway lumens. Employing cultures of airway
      epithelial cells that grow like "islands" and exhibit a continuum of cellular
      differentiation, we studied the mechanisms that render well differentiated cells
      more difficult to transfect with cationic liposomes than poorly differentiated
      cells. The poorly differentiated cells at the edge of the islands were
      transfectable with liposome-DNA complexes (pCMVbeta:LipofectACE = 1:5 (w/w)),
      whereas the more differentiated cells in the center of the islands were not.
      Evaluation of the steps leading to lipid-mediated transfection revealed that edge
      cells bound more liposome-DNA complexes, in part due to a more negative surface
      charge (as measured by cationized ferritin binding), and that edge cells
      internalized more liposome-DNA complexes than central cells. Edge cells exhibited
      receptor-mediated endocytosis of LDL, pinocytosis of 10-nm microspheres, and
      phagocytosis of 2-microm microspheres, whereas central cells were only capable of
      receptor-mediated endocytosis. Cytochalasin B, which inhibited pinocytosis by 65%
      and phagocytosis by 93%, decreased edge cell liposome-DNA complex entry by 50%.
      Potassium depletion, which decreased phagocytosis by >90% but had no effect on
      pinocytosis, inhibited edge cell liposome-DNA complex entry by 71%. These results
      indicate that liposome-DNA complexes enter edge cells via phagocytosis and that
      this pathway is not detectable in central cells. In conclusion, both reduced
      negative surface charge and absence of phagocytosis internalization pathways in
      relatively differentiated cells may explain differentiation-dependent decrements
      in cationic liposome-mediated gene transfer in airway epithelia.

PMID- 8995413
TI  - Defining the active site of yeast seryl-tRNA synthetase. Mutations in motif 2
      loop residues affect tRNA-dependent amino acid recognition.
AB  - The active site of class II aminoacyl-tRNA synthetases contains the motif 2 loop,
      which is involved in binding of ATP, amino acid, and the acceptor end of tRNA. In
      order to characterize the active site of Saccharomyces cerevisiae seryl-tRNA
      synthetase (SerRS), we performed in vitro mutagenesis of the portion of the SES1
      gene encoding the motif 2 loop. Substitutions of amino acids conserved in the
      motif 2 loop of seryl-tRNA synthetases from other sources led to loss of
      complementation of a yeast SES1 null allele strain by the mutant yeast SES1
      genes. Steady-state kinetic analyses of the purified mutant SerRS proteins
      revealed elevated Km values for serine and ATP, accompanied by decreases in kcat
      (as expected for replacement of residues involved in aminoacyl-adenylate
      formation). The differences in the affinities for serine and ATP, in the absence
      and presence of tRNA are consistent with the proposed conformational changes
      induced by positioning the 3'-end of tRNA into the active site, as observed
      recently in structural studies of Thermus thermophilus SerRS (Cusack, S.,
      Yaremchuk, A., and Tukalo, M. (1996) EMBO J. 15, 2834-2842). The crystal
      structure of this moderately homologous prokaryotic counterpart of the yeast
      enzyme allowed us to produce a model of the yeast SerRS structure and to place
      the mutations in a structural context. In conjunction with structural data for T.
      thermophilus SerRS, the kinetic data presented here suggest that yeast seryl-tRNA
      synthetase displays tRNA-dependent amino acid recognition.

PMID- 8995412
TI  - An active site substitution, F87V, converts cytochrome P450 BM-3 into a regio-
      and stereoselective (14S,15R)-arachidonic acid epoxygenase.
AB  - Cytochrome P450 BM-3 catalyzes the high turnover regio- and stereoselective
      metabolism of arachidonic and eicosapentaenoic acids. To map structural
      determinants of productive active site fatty acid binding, we mutated two amino
      acid residues, arginine 47 and phenylalanine 87, which flank the surface and heme
      ends of the enzyme's substrate access channel, respectively. Replacement of
      arginine 47 with glutamic acid resulted in a catalytically inactive mutant.
      Replacement of arginine 47 with alanine yielded a protein with reduced substrate
      binding affinity and arachidonate sp3 carbon hydroxylation activity (72% of
      control wild type). On the other hand, arachidonic and eicosapentaenoic acid
      epoxidation was significantly enhanced (154 and 137%, of control wild type,
      respectively). As with wild type, the alanine 47 mutant generated (18R)
      hydroxyeicosatetraenoic, (14S,15R)-epoxyeicosatrienoic, and (17S,18R)
      epoxyeicosatetraenoic acids nearly enantiomerically pure. Replacement of
      phenylalanine 87 with valine converted cytochrome P450 BM-3 into a regio- and
      stereoselective arachidonic acid epoxygenase ((14S,15R)-epoxyeicosatrienoic acid,
      99% of total products). Conversely, metabolism of eicosapentaenoic acid by the
      valine 87 mutant yielded a mixture of (14S,15R)- and (17S,18R)
      epoxyeicosatetraenoic acids (26 and 69% of total, 94 and 96% optical purity,
      respectively). Finally, replacement of phenylalanine 87 with tyrosine yielded an
      inactive protein. We propose that: (a) fatty acid oxidation by P450 BM-3 is
      incompatible with the presence of residues with negatively charged side chains at
      the surface opening of the substrate access channel or a polar aromatic side
      chain in the vicinity of the heme iron; (b) the high turnover regio- and
      stereoselective metabolism of arachidonic and eicosapentaenoic acids involves
      charge-dependent anchoring of the fatty acids at the mouth of the access channel
      by arginine 47, as well as steric gating of the heme-bound oxidant by
      phenylalanine 87; and (c) substrate binding coordinates, as opposed to oxygen
      chemistries, are the determining factors responsible for reaction rates, product
      chemistry, and, thus, catalytic outcome.

PMID- 8995414
TI  - A carboxyl-terminal domain in fibroblast growth factor (FGF)-2 inhibits FGF-1
      release in response to heat shock in vitro.
AB  - The fibroblast growth factor (FGF) prototypes, FGF-1 and FGF-2, lack a signal
      sequence, but both contain a nuclear localization sequence. We prepared a series
      of FGF-1 deletion mutants fused to the reporter gene, beta-galactosidase (beta
      gal) and determined that a domain between residues 83 and 154 is responsible for
      FGF-1 cytosol retention in NIH 3T3 cells. Using a series of FGF-beta-gal chimeric
      proteins prepared by the shuffling of cassette-formatted synthetic FGF prototype
      genes, we were able to demonstrate that the nuclear localization sequence from
      the 5'-CUG region of FGF-2 is not able to direct the nuclear association of FGF-1
      due to its inability to repress the function of the FGF-1 cytosol retention
      domain. We also observed that while the FGF-1:beta-gal chimera was released in
      response to heat shock, the FGF-2:beta-gal protein was not. Further, replacement
      of the FGF-1 cytosol retention domain with the corresponding domain from FGF-2
      repressed the release of the chimeric protein. These data suggest that the
      specificity of the stress-induced secretion pathway for FGF-1 involves a carboxyl
      terminal domain that is absent in FGF-2 and that the FGF-1 secretion pathway does
      not restrict the release of high molecular weight forms of FGF-1.

PMID- 8995415
TI  - Apurinic sites are position-specific topoisomerase II poisons.
AB  - Many anticancer drugs "poison" topoisomerase II by enhancing its double-stranded
      DNA cleavage activity. To determine whether DNA lesions act as endogenous
      topoisomerase II poisons, we characterized the effects of position-specific
      apurinic sites on enzyme activity. Lesions located within the 4-base overhang
      generated by enzyme-mediated DNA scission stimulated cleavage approximately 10-18
      fold without altering the specificity of topoisomerase II. DNA breaks were double
      stranded in nature, protein-linked, and readily reversible. In contrast, apurinic
      sites located immediately outside the cleavage overhang were inhibitory. Thus,
      apurinic sites, which are the most commonly formed lesion in DNA, are position
      specific topoisomerase II poisons. A model is proposed that encompasses the
      actions of endogenous and exogenous topoisomerase II poisons and provides a pre
      existing pathway for the cellular actions of topoisomerase II-targeted anticancer
      drugs.

PMID- 8995416
TI  - cDNA cloning and chromosomal localization of the human telencephalin and its
      distinctive interaction with lymphocyte function-associated antigen-1.
AB  - We have isolated cDNA encoding human telencephalin (TLN), a brain segment
      specific neuronal adhesion molecule. Human TLN comprises an NH2-terminal signal
      peptide, an extracellular region with nine Ig-like domains, a single
      transmembrane region, and a COOH-terminal cytoplasmic tail. The NH2-terminal five
      Ig-like domains of TLN were closely related to those of intercellular adhesion
      molecules (ICAMs)-1 and -3. The TLN gene was mapped to the human chromosome
      19p13.2, where the ICAM-1, -3, and -4 (LW) genes are located. Furthermore, we
      observed lymphocyte function-associated antigen-1 (LFA-1)-mediated adhesion of HL
      60 cells on recombinant TLN protein, as well as on ICAM-1. However, the
      interaction of TLN with LFA-1 on HL-60 cells was divalent cation-independent and
      phorbol 12-myristate 13-acetate stimulation-independent. We conclude that TLN is
      a unique neuronal member of ICAM subgroup of the Ig superfamily and propose a
      novel type of interaction between the Ig superfamily molecule and integrin, which
      does not require the activation of integrin. TLN on the surface of telencephalic
      neurons may be a target molecule in the brain for LFA-1-expressing microglia and
      leukocytes in physiological or pathological conditions.

PMID- 8995418
TI  - Mutational analysis of a plant defensin from radish (Raphanus sativus L.) reveals
      two adjacent sites important for antifungal activity.
AB  - Mutational analysis of Rs-AFP2, a radish antifungal peptide belonging to a family
      of peptides referred to as plant defensins, was performed using polymerase chain
      reaction-based site-directed mutagenesis and yeast as a system for heterologous
      expression. The strategy followed to select candidate amino acid residues for
      substitution was based on sequence comparison of Rs-AFP2 with other plant
      defensins exhibiting differential antifungal properties. Several mutations giving
      rise to peptide variants with reduced antifungal activity against Fusarium
      culmorum were identified. In parallel, an attempt was made to construct variants
      with enhanced antifungal activity by substituting single amino acids by arginine.
      Two arginine substitution variants were found to be more active than wild-type Rs
      AFP2 in media with high ionic strength. Our data suggest that Rs-AFP2 possesses
      two adjacent sites that appear to be important for antifungal activity, namely
      the region around the type VI beta-turn connecting beta-strands 2 and 3, on the
      one hand, and the region formed by residues on the loop connecting beta-strand 1
      and the alpha-helix and contiguous residues on the alpha-helix and beta-strand 3,
      on the other hand. When added to F. culmorum in a high ionic strength medium, Rs
      AFP2 stimulated Ca2+ uptake by up to 20-fold. An arginine substitution variant
      with enhanced antifungal activity caused increased Ca2+ uptake by up to 50-fold,
      whereas a variant that was virtually devoid of antifungal activity did not
      stimulate Ca2+ uptake.

PMID- 8995417
TI  - Ovarian- and somatic-specific transcripts of the mosquito clathrin heavy chain
      gene generated by alternative 5'-exon splicing and polyadenylation.
AB  - Insect oocytes are extraordinarily specialized for receptor-mediated endocytosis
      of yolk protein precursors. The clathrin heavy chain (CHC) is the major
      structural protein of coated vesicles, the principal organelles of receptor
      mediated endocytosis. To understand the role of clathrin in the development of
      the oocyte's powerful endocytotic machinery we determined the structure of the
      mosquito chc gene. The gene spans approximately 45 kilobases and its coding
      region is divided into seven exons, five of which encode the protein. Three
      distinct mature transcripts of this gene were identified in mosquito tissues. Two
      of them code isoforms of the CHC polypeptide differing in their NH2-terminal
      sequences, and are specifically expressed in female germ-line cells. The third
      transcript has a 3'-untranslated region about 1 kilobase longer than the other
      variants, and is found only in the somatic cells. Tissue-specific 5'-exon
      splicing and alternative polyadenylation of the primary transcript combine to
      give rise to these mRNAs. We identified two alternative promoters, distal and
      proximal, separated by approximately 10 kilobases involved in tissue-specific
      regulation of mosquito chc gene expression. Our data provide the first molecular
      evidence for complex structure and regulation of a chc gene, in this case
      occurring at both the transcriptional and post-transcriptional levels.

PMID- 8995419
TI  - Protease footprinting analysis of ternary complex formation by human TFIIA.
AB  - Transcription factor (TF) IIA performs two important regulatory functions during
      RNA polymerase II transcription: it is required for efficient binding of TFIID to
      a core promoter and it mediates the effects of upstream activators, both through
      direct interaction with the TATA box binding protein (TBP). To begin studying how
      TFIIA mediates these effects, we used a highly sensitive protease footprinting
      methodology to identify surfaces of human TFIIA participating in TFIIA x TBP x
      TATA ternary complex formation. Chymotrypsin and proteinase K cleavage patterns
      of TFIIA bearing a 32P-end-labeled gamma subunit revealed that amino acids 59-73
      were protected from cleavage both in the context of an immobilized ternary
      complex and in a binary complex with TBP alone. In contrast, amino acids 341-367
      in the beta portion of a 32P-labeled alpha-beta subunit were protected in the
      ternary but not in the binary complex, implying that those residues interact with
      promoter DNA. The regions of human TFIIA identified by protease footprinting are
      homologous to and encompass the yeast TFIIA residues that contact TBP and DNA in
      the recently solved crystal structure of the yeast ternary complex. The
      conservation of the regions and residues mediating complex formation implies that
      yeast and human TFIIA employ the same mechanism to stabilize the binding of TFIID
      to a core promoter.

PMID- 8995420
TI  - The mitogen-activated protein kinase and JAK-STAT signaling pathways are required
      for an oncostatin M-responsive element-mediated activation of matrix
      metalloproteinase 1 gene expression.
AB  - Both astrocytes in the central nervous system and fibroblasts in somatic tissues
      are not only the major sources of extracellular matrix components but also of
      matrix metalloproteinases (MMPs), a family of enzymes directly involved in
      extracellular matrix breakdown. We have analyzed the regulation of the expression
      of MMPs and TIMPs (tissue inhibitors of metalloproteinases) in human primary
      astrocytes stimulated with oncostatin M (OSM) and other extracellular mediators
      in comparison with normal human dermal fibroblasts. It was found that OSM
      induced/enhanced transcription of MMP-1 (interstitial collagenase) and MMP-3
      (stromelysin 1) in astrocytes, and MMP-1, MMP-9 (gelatinase B), and TIMP-1 in
      fibroblasts. Analysis of the signal transduction leading to activation of the MMP
      1 gene revealed the presence of an OSM-responsive element (OMRE) encompassing the
      AP-1 binding site and the signal transducer and activator of transcription (STAT)
      binding element, which mediate activation by OSM. OMRE is also present in the
      TIMP-1 gene promoter and, although there are some differences in these two
      motifs, both appear to be targets for the simultaneous action of OSM-induced
      nuclear effectors. The induced enhancement of transcription by synergistically
      acting AP-1 and STAT binding elements in response to OSM is Raf-dependent. Cross
      talk between the mitogen-activated protein kinase and JAK-STAT pathways is
      required to achieve maximal induction of the OMRE-driven transcription by OSM.

PMID- 8995421
TI  - Role of the occluding loop in cathepsin B activity.
AB  - Within the lysosomal cysteine protease family, cathepsin B is unique due to its
      ability to act both as an endopeptidase and a peptidyldipeptidase. This latter
      capacity to remove C-terminal dipeptides has been attributed to the presence of a
      20-residue insertion, termed the occluding loop, that blocks the primed terminus
      of the active site cleft. Variants of human procathepsin B, where all or part of
      this element was deleted, were expressed in the yeast Pichia pastoris. A mutant,
      where the 12 central residues of the occluding loop were deleted, autoprocessed,
      albeit more slowly than the wild type proenzyme, to yield a mature form of the
      enzyme with endopeptidase activity comparable with the wild-type cathepsin B, but
      totally lacking exopeptidase activity. This deletion mutant showed a 40-fold
      higher affinity for the inhibitor cystatin C, suggesting that the occluding loop
      normally restricts access of this inhibitor to the active site. In addition, the
      binding affinity of the cathepsin B propeptide, which is a potent inhibitor of
      this enzyme, was 50-fold increased, consistent with the finding that the loop
      reorients on activation of the proenzyme. These results suggest that the
      endopeptidase activity of cathepsin B is an evolutionary remnant since, as a
      consequence of its membership in the papain family, the propeptide must be able
      to bind unobstructed through the full length of the active site cleft.

PMID- 8995422
TI  - The membrane topology of GAT-1, a (Na+ + Cl-)-coupled gamma-aminobutyric acid
      transporter from rat brain.
AB  - The membrane topology of GAT-1, a sodium- and chloride-coupled gamma-aminobutyric
      acid transporter from rat brain, has been probed using N-glycosylation scanning
      mutagenesis. Overall, the results support the theoretical 12-transmembrane
      segment model. This model (based on hydropathy analysis) was originally proposed
      for GAT-1 and adopted for all other members of the sodium- and chloride-dependent
      neurotransmitter transporter superfamily. However, our data indicate that the
      loop connecting putative transmembrane domains 2 and 3, which was predicted to be
      located intracellularly, can be glycosylated in vivo. Furthermore, studies with
      permeant and impermeant methanesulfonate reagents suggest that cysteine 74,
      located in the hydrophilic loop connecting transmembrane domains 1 and 2, is
      intracellular rather than extracellular. We present a model in which the topology
      deviates from the theoretical one in the amino-terminal third of the transporter.
      It also contains 12 transmembrane segments, but the highly conserved domain 1
      does not form a conventional transmembrane alpha-helix.

PMID- 8995423
TI  - Analysis of the transmembrane topology of the glycine transporter GLYT1.
AB  - A theoretical 12-transmembrane segment model based on the hydrophobic moment has
      been proposed for the transmembrane topology of the glycine transporter GLYT1 and
      all other members of the sodium- and chloride-dependent transporter family. We
      tested this model by introducing N-glycosylation sites along the GLYT1 sequence
      as reporter for an extracellular localization and by an in vitro
      transcription/translation assay that allows the analysis of the topogenic
      properties of different segments of the protein. The data reported herein are
      compatible with the existence of 12 transmembrane segments, but support a
      rearrangement of the first third of the protein. Contrary to prediction,
      hydrophobic domain 1 seems not to span the membrane, and the loop connecting
      hydrophobic domains 2 and 3, formerly believed to be intracellular, appears to be
      extracellularly located. In agreement with the theoretical model, we provide
      evidence for the extracellular localization of loops between hydrophobic segments
      5 and 6, 7 and 8, 9 and 10, and 11 and 12.

PMID- 8995424
TI  - The DNA binding domain of hepatocyte nuclear factor 4 mediates cooperative,
      specific binding to DNA and heterodimerization with the retinoid X receptor
      alpha.
AB  - We recently showed that hepatocyte nuclear factor 4 (HNF-4) defines a unique
      subclass of nuclear receptors that exist in solution and bind DNA elements as
      homodimers (Jiang, G., Nepomuceno, L., Hopkins, K., and Sladek, F. M. (1995) Mol.
      Cell. Biol. 15, 5131-5143). In this study, we show that the dimerization domains
      of HNF-4 map to both the DNA binding and the ligand binding domain. Whereas the
      latter is critical for dimerization in solution, the DNA binding domain mediates
      cooperative, specific binding to direct repeats of AGGTCA separated by one or two
      nucleotides. Whereas amino acid residues 117-125 (the T-box/third helix region)
      are insufficient for cooperative homodimerization and high affinity DNA binding,
      residues 126-142 (encompassing the A-box region) are required. Finally, in
      contrast to the full-length receptor, the DNA binding domain of HNF-4 is capable
      of heterodimerizing with that of the retinoid X receptor alpha but not with that
      of other receptors. These results indicate that the HNF-4 DNA binding domain is
      distinct from that of other receptors and that the determinants that prevent HNF
      4 from heterodimerizing with RXR lie outside the DNA binding domain, presumably
      in the ligand binding domain.

PMID- 8995425
TI  - An interferon-gamma-activated site (GAS) is necessary for full expression of the
      mouse iNOS gene in response to interferon-gamma and lipopolysaccharide.
AB  - Mouse macrophages can be stimulated by interferon (IFN)-gamma and bacterial
      lipopolysaccharide (LPS) to produce nitric oxide (NO) as the result of expression
      of the inducible NO synthase (iNOS; EC 1.14.13.39) gene. The iNOS gene promoter
      contains a candidate gamma-interferon-activated site (GAS). In transfection
      studies reported here, it was demonstrated that a luciferase reporter-gene
      construct, containing four synthetic copies of the iNOS GAS, was inducible when
      transfected macrophages were stimulated with either IFN-gamma, LPS, or a
      combination of the two. Consistent with this finding were other transfection
      analyses, which showed that responsiveness of the intact iNOS promoter to these
      same agents was significantly reduced when two conserved nucleotide positions
      within the GAS were mutated. Oligonucleotide probes, which mimicked the iNOS GAS,
      formed a complex with proteins that appeared in the nuclei of IFN-gamma or IFN
      gamma + LPS-treated macrophages within 30 min of stimulation, as shown by
      electrophoretic mobility shift assay. LPS alone also caused the the appearance of
      a nuclear protein capable of binding the iNOS GAS-containing oligonucleotide;
      however, in contrast to binding induced by IFN-gamma, approximately 2 h of
      stimulation with LPS were required. The protein bound to the iNOS GAS-containing
      oligonucleotide reacted specifically with an antibody raised against Stat1a,
      regardless of the stimulus used. These data collectively support the conclusion
      that binding of Stat1 alpha to the iNOS promoter's GAS is required for optimal
      induction of the iNOS gene by IFN-gamma and LPS.

PMID- 8995426
TI  - Calcium stabilizes fibrillin-1 against proteolytic degradation.
AB  - The calcium-binding epidermal growth factor (cbEGF)-like domain is a structural
      motif that is present in many matrix proteins throughout the animal kingdom from
      invertebrates to mammals. This module has been demonstrated to bind calcium in
      the micromolar range. However, little is known about the functional consequences
      of calcium binding to proteins that contain this structural element. We used
      fibrillin-1, an extracellular matrix protein consisting of approximately 60%
      cbEGF-like motifs, as a model system to study stabilizing effects of calcium in
      protease degradation assays. Authentic human fibrillin-1 and recombinant human
      fibrillin-1 subdomains, spanning the whole molecule, showed significantly slower
      proteolytic degradation in the presence of CaCl2 than in the presence of EDTA,
      demonstrating that calcium stabilizes the structure of fibrillin-1 and protects
      the molecule against proteolytic degradation. Information about cleavage sites
      protected by calcium was obtained with a new recombinant subdomain, rF17 (Asp 952
      Val 1527), comprising the longest stretch of cbEGF-like motifs in the center of
      the fibrillin-1 molecule. The most sensitive sites for trypsin and endoproteinase
      Glu-C were observed in cbEGF-like motifs 11 (Met 1034 and Asn 1046), 12 (Ser
      1103), and 17 (Thr 1318). Since most of the currently known mutations in
      fibrillin-1 are found within cbEGF-like motifs and are predicted to disrupt
      calcium binding, we suggest that these mutations render fibrillin-1 more
      susceptible to proteolytic cleavage, and this might be one of the reasons why
      these mutations result in Marfan's syndrome.

PMID- 8995427
TI  - Beryllium fluoride and phalloidin restore polymerizability of a mutant yeast
      actin (V266G,L267G) with severely decreased hydrophobicity in a subdomain 3/4
      loop.
AB  - Holmes proposed that in F-actin, hydrophobic residues in a subdomain 3/4 loop
      interact with a hydrophobic pocket on the opposing strand resulting in helix
      stabilization. We have determined how a decreased hydrophobicity of this plug
      affects yeast actin function. Cells harboring only the V266G, V266D, V266F,
      L267G, L269D, or L269K actins appear normal, although V266G cells display an
      altered budding pattern. However, V266G,L267G (GG) double mutant cells are cold
      sensitive with randomly oriented thick actin assemblies seen in rhodamine
      phalloidin-stained GG cells. V266D actin polymerizes slower than wild-type actin
      at room temperature. At 4 degrees C, not only is polymerization slowed, but there
      is also an effect on critical concentration. However, the polymerization defects
      are milder than those associated with substitution of Asp for the neighboring
      Leu267. Purified GG-actin does not polymerize in vitro alone or in the presence
      of wild-type F-actin seeds. GG-actin polymerization can be restored by larger
      amounts of wild-type actin, beryllium fluoride, or phalloidin at room
      temperature, although at 4 degrees C only phalloidin is effective. These results
      suggest that the diminished hydrophobicity of the plug in GG-actin leads to
      filament destabilization. However, the V266D actin results require a modification
      of the original Holmes filament model.

PMID- 8995428
TI  - Sialic acid specificity of myelin-associated glycoprotein binding.
AB  - Myelin-associated glycoprotein (MAG), a nervous system cell adhesion molecule, is
      an I-type lectin that binds to sialylated glycoconjugates, including gangliosides
      bearing characteristic structural determinants (Yang, L. J.-S., Zeller, C. B.,
      Shaper, N. L., Kiso, M., Hasegawa, A., Shapiro, R. E., and Schnaar, R. L. (1996)
      Proc. Natl. Acad. Sci. U.S.A. 93, 814-818). Two cell adhesion systems, COS-1
      monkey kidney fibroblasts transiently transfected to express MAG and Chinese
      hamster ovary (CHO) cells stably transfected to express MAG, were used to probe
      the structural specificity of MAG-ganglioside binding. Both cell types bound to
      the same gangliosides: GQ1b alpha (IV3NeuAc,III6NeuAc,II3(NeuAc)2Gg4Cer) > GT1b =
      GD1a > GM3 > GM1, GD1b, and GQ1b (the latter do not support adhesion). Binding
      was enhanced by pretreatment of MAG-expressing cells with neuraminidase. MAG
      expressing Chinese hamster ovary cells bound directly to gangliosides resolved on
      thin layer chromatograms, allowing detection of MAG binding species in a mixture.
      The simplest ganglioside ligand for MAG was GM3 bearing N-acetylneuraminic acid,
      whereas GM3 bearing N-glycolylneuraminic acid did not support adhesion. Chemical
      modifications of N-acetylneuraminic acid residues (on GD1a) abrogated MAG
      binding. Mild periodate oxidation of sialic acids to their corresponding seven
      carbon (or eight-carbon) sialic acid aldehydes abolished MAG binding, as did
      further conversion to the corresponding primary alcohols. Eliminating the anionic
      charge by ethyl esterification, amidation, or reduction also abolished MAG
      mediated cell adhesion. These data demonstrate that MAG-ganglioside binding is
      highly specific and defines key carbohydrate structural determinants for MAG
      mediated cell adhesion to gangliosides.

PMID- 8995429
TI  - Overproduction and affinity purification of Saccharomyces cerevisiae replication
      factor C.
AB  - Yeast replication factor C (RF-C) is a heteropentamer encoded by the RFC1-5
      genes. RF-C activity in yeast extracts was overproduced about 80-fold after
      induction of a strain containing all five genes on a single plasmid, with
      expression of each gene placed under control of the galactose-inducible GAL1-10
      promoter. This strongly indicates that overexpression of the five known RFC genes
      is sufficient for overproduction of RF-C. Overexpression of all five genes was
      also necessary to achieve overproduction of RF-C as omission of any single gene
      from the plasmid gave uninduced, i.e. normal cellular levels of RF-C. The
      interaction between RF-C and proliferating cell nuclear antigen (PCNA) was
      studied with PCNA-agarose beads. Binding of RF-C to PCNA-agarose beads is
      negligible in buffers containing 0.3 M NaCl. However, addition of Mg-ATP to the
      binding buffer caused strong binding of RF-C to the beads even at 0.8 M NaCl.
      Binding of ATP, but not its hydrolysis, was required for the strong binding mode
      as nonhydrolyzable analogs were also effective. The existence of two distinct
      binding modes between PCNA and RF-C was used as the key step in a greatly
      improved procedure for the purification of RF-C. RF-C from the overproduction
      strain purified by this procedure was essentially homogeneous and had a
      severalfold higher specific activity than RF-C preparations that had previously
      been purified through multicolumn procedures.

PMID- 8995430
TI  - Peroxovanadate induces tyrosine phosphorylation of multiple signaling proteins in
      mouse liver and kidney.
AB  - The intraperitoneal injection of a vanadate/H2O2 mixture (peroxovanadate) into
      mice resulted within minutes in the appearance of numerous tyrosine
      phosphorylated proteins in the liver and kidney. These effects are presumably due
      to the inhibition of phosphotyrosine phosphatase activity. Three of the tyrosine
      phosphorylated proteins have been identified as the receptors for epidermal
      growth factor, insulin, and hepatocyte growth factor. The injection of
      peroxovanadate also enhanced the tyrosine phosphorylation of many of the proteins
      known to function downstream of these receptors, including SHC, signal transducer
      and activator of transcription (Stat) 1alpha,beta, Stat 3, Stat 5, phospholipase
      C-gamma, insulin receptor substrate 1, GTPase-activating protein, beta-catenin,
      gamma-catenin, p120cas, SHP-1, and SHP-2. The administration of peroxovanadate
      also induced nuclear translocation of a number of tyrosine-phosphorylated Stat
      proteins. In addition, the global effects on tyrosine phosphorylation permitted
      the detection of a number of novel intracellular protein interactions, including
      an association of Tyk2 with beta-catenin. The in situ administration of
      peroxovanadate may prove useful in the search for novel tyrosine-phosphorylated
      proteins and the identification of new interactions between previously identified
      tyrosine-phosphorylated substrates.

PMID- 8995431
TI  - Pasteurella multocida toxin activates the inositol triphosphate signaling pathway
      in Xenopus oocytes via G(q)alpha-coupled phospholipase C-beta1.
AB  - Pasteurella multocida toxin (PMT) has been hypothesized to cause activation of a
      GTP-binding protein (G-protein)-coupled phosphatidylinositol-specific
      phospholipase C (PLC) in intact cells. We used voltage-clamped Xenopus oocytes to
      test for direct PMT-mediated stimulation of PLC by monitoring the endogenous Ca2+
      dependent C1- current. Injection of PMT induced an inward, two-component Cl-
      current, similar to that evoked by injection of IP3 through intracellular Ca2+
      mobilization and Ca2+ influx through voltage-gated Ca2+ channels. These PMT
      induced currents were blocked by specific inhibitors of Ca2+ and Cl- channels,
      removal of extracellular Ca2+, or chelation of intracellular Ca2+. Specific
      antibodies directed against an N-terminal, but not a C-terminal, peptide of PMT
      inhibited the toxin-induced currents, implicating that the N terminus of PMT is
      important for toxin activity. Injection with specific antibodies against
      PLCbeta1, PLCbeta2, PLCbeta3, or PLCgamma1 identified PLCbeta1 as the primary
      mediator of the PMT-induced Cl- currents. Injection with guanosine 5'-O-(2
      (thio)diphosphate), antibodies to the common GTP-binding region of G-protein
      alpha subunits, or antibodies to different regions of G-protein beta subunits
      established the involvement of a G-protein alpha subunit in PMT-activation of
      PLCbeta1. Injection with specific antibodies against the alpha-subunits of
      G(q/11), G(s/olf), G(i/o/t/z), or G(i-1/i-2/i-3) isoforms confirmed the
      involvement of Gq/11alpha. Preinjection of oocytes with pertussis toxin enhanced
      the PMT response. Overexpression of G(q)alpha in oocytes could enhance the PMT
      response by 30-fold to more than 300-fold, whereas introduction of antisense
      G(q)alpha cRNA reduced the response by 7-fold. The effects of various specific
      antibodies on the PMT response were reproduced in oocytes overexpressing
      G(q)alpha.

PMID- 8995432
TI  - Subunit interactions of endothelial nitric-oxide synthase. Comparisons to the
      neuronal and inducible nitric-oxide synthase isoforms.
AB  - Endothelial nitric-oxide synthase (eNOS) is comprised of two identical subunits.
      Each subunit has a bidomain structure consisting of an N-terminal oxygenase
      domain containing heme and tetrahydrobiopterin (BH4) and a C-terminal reductase
      domain containing binding sites for FAD, FMN, and NADPH. Each subunit is also
      myristoylated and contains a calmodulin (CaM)-binding site located between the
      oxygenase and reductase domains. In this study, wild-type and mutant forms of
      eNOS have been expressed in a baculovirus system, and the quaternary structure of
      the purified enzymes has been analyzed by low temperature SDS-PAGE. eNOS dimer
      formation requires incorporation of the heme prosthetic group but does not
      require myristoylation or CaM or BH4 binding. In order to identify domains of
      eNOS involved in subunit interactions, we have also expressed eNOS oxygenase and
      reductase domain fusion proteins in a yeast two-hybrid system. Corresponding
      human neuronal NOS (nNOS) and murine inducible NOS (iNOS) fusion proteins have
      also been expressed. Comparative analysis of NOS domain interactions shows that
      subunit association of eNOS and nNOS involves not only head to head interactions
      of oxygenase domains but also tail to tail interactions of reductase domains and
      head to tail interactions between oxygenase and reductase domains. In contrast,
      iNOS subunit association involves only oxygenase domain interactions.

PMID- 8995433
TI  - Interferon gamma-dependent induction of human intercellular adhesion molecule-1
      gene expression involves activation of a distinct STAT protein complex.
AB  - In response to interferon gamma (IFNgamma), intercellular adhesion molecule-1
      (ICAM-1) is expressed on human keratinocytes, a cell type that is critically
      involved in cutaneous inflammation. An ICAM-1 5' regulatory region palindromic
      response element, pIgammaRE, has been shown to confer IFNgamma-dependent
      transcription enhancement. By electrophoretic mobility shift assays (EMSA),
      pIgammaRE forms a distinct complex with proteins from IFNgamma-treated human
      keratinocytes, termed gamma response factor (GRF). Binding of GRF is tyrosine
      phosphorylation-dependent, and mutations of pIgammaRE that disrupt the
      palindromic sequence or alter its spatial relationship abrogate GRF binding.
      Supershift EMSAs using antibodies to characterized STAT proteins suggest that GRF
      contains a Stat1alpha-like protein; however, non-ICAM-1 IFNgamma-responsive
      elements (REs) known to bind Stat1alpha homodimers fail to compete for GRF
      binding in EMSA, and pIgammaRE does not cross-compete with these REs that complex
      with homodimeric stat1alpha. The pIgammaRE x GRF complex also displays a
      distinctly different electrophoretic mobility compared to that of IFNgammaREs
      complexed to homodimeric Stat1alpha. These findings indicate that a distinct
      complex containing a Stat1alpha-like protein mediates IFNgamma-induced ICAM-1
      gene transcription and identifies a subset of IFNgamma-responsive genes that
      appear to be regulated by this complex.

PMID- 8995434
TI  - A model for the double-stranded RNA (dsRNA)-dependent dimerization and activation
      of the dsRNA-activated protein kinase PKR.
AB  - Binding of double-stranded RNA (dsRNA) to PKR induces autophosphorylation and
      activation. However, the requirement for dsRNA in promoting dimerization and the
      requirement for dimerization in PKR activation are controversial. We have studied
      the dsRNA binding and dimerization requirements for the activation of PKR in
      vivo. Co-expression and immunoprecipitation experiments detected an interaction
      between the K296P mutant and a bacteriophage T7-epitope-tagged K64E mutant of
      dsRNA binding domain. In contrast, the K64E/K296P double mutant did not form a
      detectable dimer with the wild-type dsRNA binding domain. These results support
      that dimerization of intact PKR with the isolated dsRNA binding domain requires
      dsRNA binding activity. Expression of the isolated PKR kinase domain (residues
      228-551) reduced translation of the reporter mRNA even in the presence of PKR
      inhibitors. Furthermore, the isolated kinase domain (residues 228-551) undergoes
      autophosphorylation and sequentially transphosphorylates both mutant K296P PKR
      and wild-type eIF-2alpha in vitro. In contrast, the isolated kinase domain
      (residues 264-551) lacking the third basic region was not active. These
      observations lead us to propose that the dsRNA binding domains on intact PKR
      inhibit kinase activity and that dsRNA binding to intact PKR induces a
      conformational change to expose dimerization sites within the dsRNA binding
      domain thereby promoting dimerization and facilitating trans-phosphorylation and
      activation.

PMID- 8995435
TI  - A lymphocyte-specific Ltk tyrosine kinase isoform is retained in the endoplasmic
      reticulum in association with calnexin.
AB  - A lymphocyte-specific murine Ltk tyrosine kinase isoform was previously found to
      reside in the endoplasmic reticulum and to be potently activated upon treatment
      of cells with alkylating or thiol-oxidizing agents. Based on these observations,
      a unique role for Ltk was proposed as an endoplasmic reticulum-resident
      transmembrane kinase regulated by redox changes (Bauskin, A. R., Alkalay, I., and
      Ben-Neriah, Y. (1991) Cell 66, 685-696). To analyze why this Ltk isoform is
      retained in the endoplasmic reticulum, we investigated its behavior in over
      expressing cells. Our results indicate that lymphoid Ltk exhibits a dual
      Nexo/Ccyt and Ncyt/Cexo transmembrane topology in transfected cells. This unusual
      behavior may be responsible for retention in the endoplasmic reticulum since
      mutants with an increased number of positive amino acids downstream of the
      transmembrane segment exhibit a conventional Nexo/Ccyt orientation and proceed to
      the cell surface. Endoplasmic reticulum-retained Ltk forms a prominent complex
      with the chaperone calnexin, suggesting that Ltk may be retained by the mechanism
      that prevents surface expression of inappropriately folded proteins or
      incompletely assembled protein complexes.

PMID- 8995436
TI  - Substrate binding by human apurinic/apyrimidinic endonuclease indicates a Briggs
      Haldane mechanism.
AB  - Apurinic/apyrimidinic endonuclease (AP endo) makes a single nick 5' to a DNA
      abasic site. We have characterized this reaction by steady-state and transient
      state kinetics with purified human AP endo, which had been expressed in
      Escherichia coli. The substrate was a 49-base pair oligonucleotide with an abasic
      site at position 21. This substrate was generated by treating a 49-mer duplex
      oligonucleotide with a single G/U located at position 21 with uracil-DNA
      glycosylase. The enzymatic products of the AP endo nicking reaction were a 20-mer
      with a hydroxyl group at the 3'-terminus and a 28-mer with a phosphodeoxyribose
      at the 5'-terminus. To obtain maximal enzymatic activity, it was necessary to
      stabilize the abasic site during treatment with uracil-DNA glycosylase with a
      reducing agent. Otherwise, a 20-mer with phosphoribose at the 3'-terminus
      resulted from beta-elimination. In agreement with others, Km and kcat were 100 nM
      and 10 s(-1), respectively. Heat treatment of the abasic site-containing 49-mer
      without enzyme also resulted in conversion to the beta-elimination product. The
      resultant heat degradation product was an efficient inhibitor of AP endo with a
      Ki of 30 nM. The enzyme required divalent cation (Mg2+) for activity, but bound
      substrate DNA in the absence of Mg2+. Electrophoretic mobility shift assays
      indicated that AP endo bound tightly to DNA containing an abasic site and formed
      a 1:1 complex at low enzyme concentrations. The association and dissociation rate
      constants for substrate binding to AP endo were determined by using a challenge
      assay to follow AP endo-substrate complex formation. Heat degradation product
      together with heparin served as an effective trap for free enzyme. The results
      are consistent with a Briggs-Haldane mechanism where k(on) and k(off) are 5 x
      10(7) M(-1) s(-1) and 0.04 s(-1), respectively (Kd = 0.8 nM), kcat is 10 s(-1),
      and product release is very rapid (i.e. k(off,product) >> 10 s(-1)). This scheme
      is in excellent agreement with the measured steady-state kinetic parameters.

PMID- 8995437
TI  - Involvement of the Sp3 transcription factor in induction of p21Cip1/WAF1 in
      keratinocyte differentiation.
AB  - The cyclin-dependent kinase inhibitor p21 is induced in several in vitro terminal
      differentiation systems as well as in differentiating tissues in vivo. To
      determine the mechanism responsible for p21 induction during differentiation of
      mouse primary keratinocytes, we performed a deletion analysis of the p21
      promoter. The minimal region of the p21 promoter required for its induction in
      keratinocyte differentiation consists of a contiguous stretch of 78 base pairs,
      which contains a GC-rich region as well as the TATA box. We determined that
      transcription factors Sp1 and Sp3, present in primary keratinocyte nuclear
      extracts, bind the GC region concomitantly. Expression studies established that
      both Sp1 and Sp3 activate the p21 promoter, but showed that only Sp3
      overexpression enhances promoter inducibility during differentiation.
      Furthermore, disruption of the GC-rich region dramatically decreases
      transcription factor binding as well as promoter activity and inducibility upon
      differentiation. The overexpression of either Sp1 or Sp3 restores the basal
      activity of the disrupted promoter, but only Sp3 can restore its inducibility.
      These findings show that both Sp1 and Sp3 can contribute to the basal activity of
      the p21 promoter, and establish Sp3 as a specific transcription factor involved
      in the induction of p21 promoter during keratinocyte differentiation.

PMID- 8995438
TI  - Characterization of the genomic structure, promoter region, and a tetranucleotide
      repeat polymorphism of the human neurotensin receptor gene.
AB  - In the present study, we have cloned the human neurotensin receptor (NTR) gene,
      determined its structure, demonstrated that its promoter is functional in
      transfection experiments, and identified the start site of transcription and a
      tetranucleotide repeat polymorphism that locates at less than 3 kilobase pairs
      from the gene. The gene contains three introns, all in the coding regions.
      Several differences in genomic clones and previously characterized cDNA sequences
      are reconciled. The 5' regulatory region, which is rich in presumptive
      transcription factors, can drive luciferase expression in transfected CHO-K1
      cells. Stepwise 5' deletions identify a positive modulator between -782 and -1309
      and a negative modulator between -1309 and -1563. Southern blot analyses
      demonstrate a single copy gene for the NTR. The tetranucleotide repeat
      polymorphism is highly informative with at least 23 alleles and might serve as a
      very useful marker for genetic study of the relationship between the NTR and
      neuropsychiatric disorders.

PMID- 8995440
TI  - Tumor necrosis factor-alpha regulation of glucose transporter (GLUT1) mRNA
      turnover. Contribution of the 3'-untranslated region of the GLUT1 message.
AB  - In the current study we report on the contribution of the GLUT1 3'-untranslated
      region (UTR) to the stability of the GLUT1 mRNA. To facilitate these
      investigations, a hybrid construct was prepared by insertion of the GLUT1 3'-UTR
      into a normally stable reporter gene coding for preproinsulin. The GLUT1 3'-UTR
      conferred lability to the otherwise long lived construct and transferred an
      ability to be stabilized in response to treatment with the cytokine, tumor
      necrosis factor-alpha (TNF). The destabilizing element has been mapped to a
      region located between bases 2242 and 2347 of the GLUT1 3'-UTR; this same region
      also mediates the stabilization response to TNF. In vitro RNA-protein binding
      assays using protein extracts from control and TNF-treated cells demonstrated
      that two proteins, one of 37 kDa and the other of 40 kDa, recognized sequence
      elements within the stability-determining region and were up-regulated in
      response to TNF treatment. The RNA-binding activity of these proteins coincides
      with the stabilization of the GLUT1 message, suggesting that they may be involved
      in regulation of the turnover of this message.

PMID- 8995439
TI  - Stimulation of platelet activation and aggregation by a carboxyl-terminal peptide
      from thrombospondin binding to the integrin-associated protein receptor.
AB  - Thrombospondin, a major secretory product of the alpha-granules of activated
      platelets, is a large trimeric glycoprotein that plays an important role in
      platelet aggregation. On resting platelets, thrombospondin binds to a single
      receptor in a cation-independent manner, but upon platelet activation it binds at
      least two further, distinct receptors that are both dependent upon divalent
      cations. Each of these receptors on the platelet surface binds to different
      regions of the thrombospondin molecule, and such binding may be responsible for
      the multifunctional role of thrombospondin in aggregation. We show here that a
      peptide from the carboxyl terminus of thrombospondin, RFYVVMWK, directly and
      specifically induces the activation and aggregation of washed human platelets
      from different donors at concentrations of 5-25 microM. At lower concentrations
      the peptide synergizes with suboptimal concentrations of ADP to induce
      aggregation. Peptide affinity chromatography and immunoprecipitation with a
      monoclonal antibody were used to identify the receptor for the carboxyl-terminal
      peptide as the integrin-associated protein. The integrin-associated protein
      remained bound to the RFYVVMWK-containing peptide column when washed with a
      scrambled peptide in the presence of 5 mM EDTA, indicating a divalent cation
      independent association. It is suggested that integrin-associated protein is the
      primary receptor for thrombospondin on the surface of resting platelets and is
      implicated in potentiating the platelet aggregation response.

PMID- 8995442
TI  - Endoprotease activities other than furin and PACE4 with a role in processing of
      HIV-I gp160 glycoproteins in CHO-K1 cells.
AB  - We addressed the question of whether furin is the endoprotease primarily
      responsible for processing the human immunodeficiency virus type I (HIV-I)
      envelope protein gp160 in mammalian cells. The furin-deficient Chinese hamster
      ovary (CHO)-K1 strain RPE.40 processed gp160 as efficiently as wild-type CHO-K1
      cells in vivo. Although furin can process gp160 in vitro, this processing is
      probably not physiologically relevent, because it occurs with very low
      efficiency. PACE4, a furin homologue, allowed processing of gp160 when both were
      expressed in RPE.40 cells. Further, PACE4 participated in the activation of a
      calcium-independent protease activity in RPE.40 cells, which efficiently
      processed the gp160 precursor in vitro. This calcium-independent protease
      activity was not found in another furin-deficient cell strain, 7.P15, selected
      from the monkey kidney cell line COS-7.

PMID- 8995441
TI  - Intramolecular chaperone activity of the pro-region of Vibrio cholerae El Tor
      cytolysin.
AB  - Vibrio cholerae synthesizes a toxin named El Tor cytolysin/hemolysin, which lyses
      erythrocytes and other mammalian cells. This toxin is encoded by the hlyA gene
      and is synthesized as a precursor form, prepro-HlyA. Prepro-HlyA consists of,
      from the amino terminus of this protein, a signal peptide, a pro-region, and a
      mature region. The pro-region is cleaved off extracellularly resulting in
      activation. To analyze the role of the pro-region, we substituted the native hlyA
      gene with the pro-region-deleted hlyA gene (hlyA delta pro). The hemolytic
      activity of the mutant organism was markedly decreased; the product of the hlyA
      delta pro gene, secreted in the periplasm, was degraded. To compare their
      abilities to form tertiary structure, the purified mature- and pro-HlyA were
      denatured and then renatured by reducing the concentration of denaturant; the
      denatured pro-HlyA recovered almost all activity while the mature-HlyA was not
      renatured. The sequences of the pro-region and a molecular chaperone, Hsp90, were
      similar. The pro-region expressed in Escherichia coli containing the hlyA delta
      pro gene increased the cytolytic activity. The purified pro-region peptide also
      facilitated renaturation of the denatured mature HlyA. These results suggest that
      the pro-region possibly guides the folding of the cytolysin similar to a
      molecular chaperone; the pro-region and molecular chaperones share common
      function and structure.

PMID- 8995443
TI  - Inhibition of endogenous ganglioside synthesis does not block neurite formation
      by retinoic acid-treated neuroblastoma cells.
AB  - Gangliosides are believed to play a critical role in cellular differentiation. To
      test this concept, we determined the effect of inhibition of endogenous
      ganglioside synthesis upon neurite formation induced by retinoic acid in LAN-5
      human neuroblastoma cells. Ganglioside synthesis and content of LAN-5 cells
      exposed for 6 days to 10 microM D-threo-1-phenyl-2-decanoylamino-3-morpholino-1
      propanol (D-PDMP) (an inhibitor of glucosylceramide synthase) were reduced by
      >90%. However, these ganglioside-depleted cells were not blocked from forming
      neurites when exposed to 10 microM retinoic acid. Even more extensive treatment
      of LAN-5 cells with 20 microM D-PDMP (6 day pretreatment followed by 6 days
      together with 10 microM retinoic acid) still did not block the retinoic acid
      induced neurite formation. An element of neuroblastoma tumor cell
      differentiation, neurite formation, is therefore dependent neither on an intact
      cellular ganglioside complement nor on new ganglioside synthesis.

PMID- 8995444
TI  - Chk, a Csk family tyrosine protein kinase, exhibits Csk-like activity in
      fibroblasts, but not in an antigen-specific T-cell line.
AB  - The Csk family of tyrosine protein kinases comprises two members named Csk and
      Chk. These enzymes phosphorylate the carboxyl-terminal tyrosine of Src-related
      kinases in vitro, thereby repressing their activity. Csk has been found to be
      necessary for normal embryonic development, and to be a potent negative regulator
      of antigen receptor signaling in T-lymphocytes. As the functions of Chk in
      mammalian cells are not known, we examined its ability to carry out Csk-like
      functions in vivo. Like p50csk, Chk reduced the elevated phosphotyrosine levels
      and the augmented activity of Src family kinases in Csk-deficient fibroblasts.
      Contrary to Csk, however, Chk was inefficient at repressing antigen receptor
      induced signals in a T-cell line (BI-141). We also noted that Chk, but not Csk,
      failed to stably associate with cellular membranes following addition of a
      membrane targeting signal to its amino terminus. This observation suggested that
      Chk may contain dominant targeting sequences disallowing its recruitment to
      cellular membranes. Hence, these data demonstrate that Chk can mediate some, but
      not all, Csk-related functions in vivo. Moreover, they suggest that the
      "restricted" function of Chk may relate at least in part to its inability to be
      recruited to certain cellular locales.

PMID- 8995445
TI  - SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein
      tyrosine kinases in rat basophilic leukemia cells.
AB  - Stimulation of the IgE high affinity receptor on rat basophilic leukemia RBL-2H3
      cells results in activation of protein tyrosine kinases and rapid tyrosine
      phosphorylation of several substrates, many of which remain unidentified. In this
      report, we demonstrate that the Grb2 adapter protein, when expressed as a
      glutathione S-transferase fusion protein, associates with four tyrosine
      phosphorylated molecules (116, 76, 36, and 31 kDa) from lysates of stimulated RBL
      2H3 cells. We show further that the 76-kDa protein is SLP-76, a hematopoietic
      cell-specific protein first identified as a Grb2-binding protein in T cells. Upon
      stimulation of the high affinity receptor for IgE, SLP-76 undergoes rapid
      tyrosine phosphorylation and associates with two additional tyrosine
      phosphoproteins of 62 and 130 kDa via the SH2 domain of SLP-76. Additional
      studies demonstrate that the SLP-76 SH2 domain also binds a protein kinase from
      stimulated RBL-2H3 cell lysates. Furthermore, the phosphorylation of SLP-76
      requires Syk activity but is not dependent on Ca+2 mobilization. These data,
      together with our previous work documenting its role in T-cell activation,
      suggest that SLP-76 and the proteins with which it associates may play a
      fundamental role in coupling signaling events in multiple cell types in the
      immune system.

PMID- 8995446
TI  - The dual specificity mitogen-activated protein kinase phosphatase-1 and -2 are
      induced by the p42/p44MAPK cascade.
AB  - Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) and MKP-2 are two
      members of a recently described family of dual specificity phosphatases that are
      capable of dephosphorylating p42/p44MAPK. Overexpression of MKP-1 or MKP-2
      inhibits MAP kinase-dependent intracellular signaling events and fibroblast
      proliferation. By using specific antibodies that recognize endogenous MKP-1 and
      MKP-2 in CCL39 cells, we show that MKP-1 and MKP-2 are not expressed in quiescent
      cells, but are rapidly induced following serum addition, with protein detectable
      as early as 30 min (MKP-1) or 60 min (MKP-2). Serum induction of MKP-1 and MKP-2
      is sustained, with protein detectable up to 14 h after serum addition. Induction
      of MKP-1 and, to a lesser extent, MKP-2 temporally correlates with p42/p44MAPK
      inactivation. To analyze the contribution of the MAP kinase cascade to MKP-1 and
      MKP-2 induction, we examined CCL39 cells transformed with either v-ras or a
      constitutively active direct upstream activator of MAP kinase, mitogen-activated
      protein kinase kinase-1 (MKK-1; MKK-1(SD/SD) mutant). In both cell models, MKP-1
      and MKP-2 are constitutively expressed, with MKP-2 being prevalent. In addition,
      in CCL39 cells expressing an estradiol-inducible deltaRaf-1::ER chimera,
      activation of Raf alone is sufficient to induce MKP-1 and MKP-2. The role of the
      MAP kinase cascade in MKP induction was highlighted by the MKK-1 inhibitor PD
      098059, which blunted both the activation of p42/p44MAPK and the induction of MKP
      1 and MKP-2. However, the MAP kinase cascade is not absolutely required for the
      induction of MKP-1, as this phosphatase, but not MKP-2, was induced to detectable
      levels by agents that stimulate protein kinases A and C. Thus, activation of the
      p42/p44MAPK cascade promotes the induction of MKP-1 and MKP-2, which may then
      attenuate p42/p44MAPK-dependent events in an inhibitory feedback loop.

PMID- 8995447
TI  - Insulin receptor substrate-2 is the major 170-kDa protein phosphorylated on
      tyrosine in response to cytokines in murine lymphohemopoietic cells.
AB  - Insulin receptor substrate 1 (IRS-1), and its structural relative IRS-2, are both
      phosphorylated on tyrosine following treatment of cells with interleukin-4 (IL-4)
      and insulin. We have investigated whether both IRS-1 and IRS-2 are expressed in
      murine lymphohemopoietic cells. T and B lymphocytes and macrophages from primary
      cultures expressed only IRS-2, which became phosphorylated on tyrosine following
      stimulation with both IL-4 and insulin. Likewise, the murine myeloid cell line FD
      5 expressed only IRS-2, which was tyrosine phosphorylated in response to IL-4 and
      insulin, as well as interleukin-3 and granulocyte-macrophage colony stimulating
      factor. Neither IRS-1 nor IRS-2 were expressed at detectable levels in primary
      bone marrow mast cells although these cells do respond to IL-4. Moreover, a
      factor-dependent lymphocyte cell line, CT.4S, which grows continuously in IL-4,
      did not express detectable levels of IRS-1 or IRS-2. IRS-2 from FD-5 cells
      stimulated with either IL-4 or insulin bound to glutathione S-transferase fusion
      proteins of the p85 subunit of phosphoinositol 3'-kinase, Grb2, and Syp,
      paralleling reported associations of IRS-1 with these molecules and indicating
      phosphorylation of the corresponding residues on IRS-2.

PMID- 8995448
TI  - Inhibition of neuronal process outgrowth and neuronal specific gene activation by
      the Brn-3b transcription factor.
AB  - The differentiation of the ND7 neuronal cell line to a nondividing phenotype
      bearing numerous neurite processes is accompanied by a dramatic increase in the
      levels of the activating POU family transcription factor Brn-3a and a
      corresponding fall in the levels of the closely related inhibitory factor Brn-3b.
      We have previously shown that the artificial overexpression of Brn-3a in these
      cells can induce neurite outgrowth and the activation of genes encoding synaptic
      vesicle proteins in the absence of a differentiation-inducing stimulus. Here we
      show that overexpression of Brn-3b can reduce process outgrowth and synaptic
      vesicle gene expression following exposure to a stimulus which would normally
      induce differentiation. These inhibitory effects are abolished by altering a
      single amino acid in the POU homeodomain of Brn-3b to its equivalent in Brn-3a.
      The converse mutation in Brn-3a allows it to inhibit process outgrowth in
      response to a differentiation-inducing stimulus. Hence a single amino acid
      difference results in these closely related factors having opposite effects and
      allows the balance between them to regulate differentiation.

PMID- 8995449
TI  - A coiled-coil tetramerization domain of BCR-ABL is essential for the interactions
      of SH2-containing signal transduction molecules.
AB  - BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase
      activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph1)
      positive leukemia. We have previously shown SH2-containing phosphotyrosine
      phosphatase SHP-2 forms stable complexes with BCR-ABL and Grb2 in BCR-ABL
      transformed cells (Tauchi, T., Feng, G. S., Shen, R., Song, H. Y., Donner, D.,
      Pawson, T., and Broxmeyer, H. E. (1994) J. Biol. Chem. 269, 15381-15387). To
      elucidate the structural requirement of BCR-ABL for the interactions with SH2
      containing signaling molecules, we examined a series of BCR-ABL mutants which
      include the Grb2 binding site-deleted BCR-ABL (1-63 BCR/ABL), the tetramerization
      domain-deleted BCR-ABL (64-509 BCR/ABL), and the SH2 domain-deleted BCR-ABL
      (BCR/ABL deltaSH2). These BCR-ABL mutants were previously shown to reduce the
      transforming activity in fibroblasts. We found that the tetramerization domain
      deleted BCR-ABL did not induce the tyrosine phosphorylation of SHP-2 and the
      interactions of BCR-ABL, SHP-2, and Grb2. In vitro kinase assays have also shown
      that the tetramerization domain-deleted BCR-ABL mutant did not phosphorylate GST
      SHP-2 in vitro. SHP-2 was co-immunoprecipitated with phosphatidylinositol 3
      kinase in BCR/ABL p210-transformed cells; however, this interaction was not
      observed in the tetramerization domain-deleted BCR-ABL mutant. Therefore the
      tetramerization domain of BCR-ABL is essential for interactions of these
      downstream molecules.

PMID- 8995450
TI  - Differential effect of shear stress on extracellular signal-regulated kinase and
      N-terminal Jun kinase in endothelial cells. Gi2- and Gbeta/gamma-dependent
      signaling pathways.
AB  - Shear stress differentially regulates production of many vasoactive factors at
      the level of gene expression in endothelial cells that may be mediated by mitogen
      activated protein kinases, including extracellular signal-regulated kinase (ERK)
      and N-terminal Jun kinase (JNK). Here we show, using bovine aortic endothelial
      cells (BAEC), that shear stress differentially regulates ERK and JNK by
      mechanisms involving Gi2 and pertussis toxin (PTx)-insensitive G-protein
      dependent pathways, respectively. Shear activated ERK with a rapid, biphasic time
      course (maximum by 5 min and basal by 30-min shear exposure) and force dependence
      (minimum and maximum at 1 and 10 dyn/cm2 shear stress, respectively). PTx
      treatment prevented shear-dependent activation of ERK1/2, consistent with a Gi
      dependent mechanism. In contrast, JNK activity was maximally turned on by a
      threshold level of shear force (0.5 dyn/cm2 or higher) with a much slower and
      prolonged time course (requiring at least 30 min to 4 h) than that of ERK. Also,
      PTx had no effect on shear-dependent activation of JNK. To further define the
      shear-sensitive ERK and JNK pathways, vectors expressing hemagglutinin epitope
      tagged ERK (HA-ERK) or HA-JNK were co-transfected with other vectors by using
      adenovirus-polylysine in BAEC. Expression of the mutant (alpha)i2(G203),
      antisense G(alpha)i2 and a dominant negative Ras (N17Ras) prevented shear
      dependent activation of HA-ERK, while that of (alpha)i2(G204) and antisense
      (alpha)i3 did not. Expression of a Gbeta/gamma scavenger, the carboxyl terminus
      of beta-adrenergic receptor kinase (betaARK-ct), and N17Ras inhibited shear
      dependent activation of HA-JNK. Treatment of BAEC with genistein prevented shear
      dependent activation of ERK and JNK, indicating the essential role of tyrosine
      kinase(s) in both ERK and JNK pathways. These results provide evidence that 1)
      Gi2-protein, Ras, and tyrosine kinase(s) are upstream regulators of shear
      dependent activation of ERK and 2) that shear-dependent activation of JNK is
      regulated by mechanisms involving Gbeta/gamma, Ras, and tyrosine kinase(s).

PMID- 8995451
TI  - Nitric oxide protects cultured rat hepatocytes from tumor necrosis factor-alpha
      induced apoptosis by inducing heat shock protein 70 expression.
AB  - Nitric oxide (NO) and tumor necrosis factor-alpha (TNFalpha) play important roles
      in the pathogenesis of liver disease during acute inflammation. The present study
      was designed to elucidate the effect of NO pre-exposure on TNFalpha-induced
      hepatotoxicity. Pretreatment of primary cultures of rat hepatocytes with the NO
      donor S-nitroso-N-acetylpenicillamine (SNAP) induced the expression of heat shock
      protein 70 (HSP70) mRNA and protein, which was associated with thermotolerance
      and cytoprotection from TNFalpha+actinomycin D-induced hepatotoxicity and
      apoptosis. SNAP transiently changed the intracellular redox state by inducing
      glutathione (GSH) oxidation associated with the formation of S-nitrosoglutathione
      (GSNO). HSP70 mRNA was also induced by the GSH-oxidizing agent diamide and the
      GSH-conjugating agent N-ethylmaleimide, suggesting that NO induces HSP70
      expression through GSH oxidation. The protective effect of SNAP pretreatment on
      TNFalpha-induced apoptosis correlated with the level of HSP70 expression. SNAP
      pretreatment inhibited reactive oxygen intermediate generation and lipid
      peroxidation effects that were reversed by blocking HSP70 expression using an
      antisense oligonucleotide to HSP70. Finally, endogenous NO formation, induced in
      hepatocytes stimulated with interferon-gamma and interleukin-1beta, led to the
      formation of GSNO and GSSG, induced HSP70, and attenuated TNFalpha-mediated
      cytotoxicity. These findings demonstrated that NO can induce resistance to
      TNFalpha-induced hepatotoxicity, possibly through the stimulation of HSP70
      expression.

PMID- 8995452
TI  - The full-scale PACS archive. A prerequisite for the filmless hospital.
AB  - PURPOSE: Increasing percentages of digital modalities in radiology, in particular
      of digital image acquisition in conventional radiography, call for digital
      reporting, communication, and archiving techniques. These techniques are
      prerequisites for the "filmless" hospital. The first 2 have been covered
      extensively in the literature and by vendors. However, as regards online digital
      image archives there are still no satisfactory concepts available in the medical
      field. The present paper puts forward some suggestions as to how this situation
      could be improved. MATERIAL AND METHODS: Analyses of radiology operations
      consider the prevailing PACS (picture archiving and communication system) archive
      concepts that use optical discs to be too small, too slow and too cumbersome to
      manage and therefore unable to function as comprehensive image archives for
      filmless hospitals. We suggest borrowing and adapting the well tested archive
      technologies from space research and the oil and broadcasting industries which
      have much higher capacities and speeds and better software interfacing
      possibilities. With such technologies the needs of filmless hospital operations
      can be met. RESULTS: A feasible concept for a transition strategy from
      conventional analog to digital archives is presented. Model calculations of the
      necessary investments and potential savings, including generous placement of
      viewing stations in the entire hospital, indicate amortization periods of 3.8-4.8
      years. CONCLUSION: Alternative technologies for digital image archives already
      today make full-scale PACS for filmless hospitals technologically and
      conceptually feasible and financially mandatory.

PMID- 8995453
TI  - ROC-analysis of detection performance by analogue and digital plain film systems
      in chest radiography.
AB  - PURPOSE: To compare the performances of 4 imaging systems in the diagnostic
      radiology of the chest: an asymmetric screen-film combination (a-SFC); a
      conventional screen-film combination of speed class 200 (SFC); a screen-film
      combination of speed class 200 with an aluminium lung filter; and digital
      luminescence radiographs (DLR). MATERIAL AND METHODS: Object detectability
      studies were carried out using an anthropomorphic chest phantom. The images were
      obtained under standard exposure conditions at 125 kVp. The detection performance
      of the various systems was evaluated by receiver operating characteristic (ROC)
      analysis on the basis of a total of 12,240 observations. RESULTS: In the overall
      evaluation the a-SFC and the SFC plus lung filter received equally high ratings
      of 0.878+/-0.018 and 0.860+/-0.21, respectively (p>0.05). There was no
      significant difference between the 200-speed SFC and the storage phosphor
      radiographs. In the mediastinum all the tested systems were clearly superior to
      the 200-speed SFC (p<0.05) while in the lung fields the 200-speed SFC received a
      high rating of 0.866+/-0.026. The a-SFC had slight advantages over the SFC plus
      lung filter and the 2 digital imaging modes (p>0.05). CONCLUSION: The a-SFC and
      the digital luminescence radiographs provide a significant gain in diagnostic
      information in the mediastinum without diminishing detail detectability in the
      lung fields and without additional radiation exposure.

PMID- 8995454
TI  - Software upgrading in a CT scanner. Influence on quantitative CT.
AB  - PURPOSE: In an attempt to improve field uniformity and CT number stability, the
      software in a CT scanner was replaced with a new version. The purpose of the
      present study was to investigate the influence of the software upgrading on
      density measurements. MATERIAL AND METHODS: The upgrading influence was
      investigated by means of a torso phantom (European spinal). The phantom simulates
      a torso which contains 3 vertebrae of different densities. RESULTS: Despite the
      use of a reference standard under the phantom, the software change resulted in:
      a) improved short-term precision; b) increased density values at 80 and 100 kVp,
      decreased at 130 kVp; and c) increased influence of the kVp on the values.
      CONCLUSION: The results of the present study suggest that conversion factors have
      to be used in density values for reference populations as well as in the values
      of patients undergoing follow-up studies.

PMID- 8995455
TI  - MR imaging in recurrent pain after back surgery. A comparative study using
      standard and high doses of gadolinium contrast agents.
AB  - PURPOSE: To compare the diagnostic results following injection of (a) a high dose
      (0.3 mmol/kg b.w.) of gadodiamide injection and (b) the standard dose (0.1
      mmol/kg b.w.) of Gd-DTPA, in patients with recurrent symptoms after surgery for
      lumbar disc herniation. MATERIAL AND METHODS: Twenty patients with recurrent or
      sustained symptoms after surgery for lumbar disc herniations were examined. MR
      imaging (0.3 T) was first performed before and after Gd-DTPA at 0.1 mmol/kg b.w.,
      and then within one month (17 patients) or within 3 months (3 patients) before
      and after gadodiamide injection at 0.3 mmol/kg b.w. The examinations were first
      evaluated by 2 neuroradiologists blinded to dose but not to patient as the images
      were presented in pairs. Six months later the same investigators evaluated the
      examinations again, this time blinded to both dose and patient. RESULTS: At the
      evaluation in pairs (with the investigators blinded to dose only) the high-dose
      examinations were considered the most informative (p=0.05). However, at the later
      evaluation (with the investigators blinded both to dose and patient) no
      significant difference between high and standard dose was found regarding
      diagnosis or diagnostic certainty. CONCLUSION: In this study the high-dose
      contrast enhancement of MR imaging at 0.3 T did not increase the diagnostic
      information for differentiating between scar and recurrent hernia. The high-dose
      images were considered more informative when evaluated in pairs, but gave no
      additional or different information when evaluated separately. The study also
      indicated that comparisons in pairs should be interpreted with caution.

PMID- 8995456
TI  - Radiological measurement of femoral head position in Legg-Calve-Perthes disease.
AB  - PURPOSE: Since the establishment of the principle of weight-bearing methods of
      treatment in Legg-Calve-Perthes disease (LCPD), lateral displacement of the
      femoral head has become an important prognostic factor. MATERIAL AND METHODS: In
      order to establish reliable boundary lines between orthotopic and subluxated hip,
      the migration percentage (MP) and the medial joint space (MJS) were determined
      retrospectively: a) on 166 normal hip radiographs; b) on bilateral arthrograms
      and radiographs from 37 patients with unilateral LCPD. RESULTS AND CONCLUSION:
      The mean upper normal values for MP and MJS on normal radiographs were 20.8 and
      11.5 respectively. On arthrograms, the corresponding values were 31 and 5.7. The
      MP is easy to determine on both radiographs and arthrograms, and is recommended
      for detecting and measuring subluxation in cases with LCPD. MJS is of no
      advantage for detecting containment in LCPD but may be used in other diseases
      such as coxitis simplex.

PMID- 8995457
TI  - Complicated bone and soft-tissue infections. Imaging with 0.1 T MR and 99mTc
      HMPAO-labeled leukocytes. ff.
AB  - PURPOSE: To assess the value of imaging by 0.1 T MR and by 99mTc-HMPAO-labeled
      leukocytes in confirming skeletal infection in patients with soft-tissue
      infections and/or bone pathology. METHODS: Thirty-nine anatomical sites (35
      patients) with suspected bone infection were prospectively imaged with 0.1 T MR
      and 99mTc-HMPAO-labeled leukocytes. Thirty-two infected areas were confirmed: 12
      osteomyelitis (out of which 3 were spondylitis) and 27 soft-tissue infections
      (both bone and soft-tissue infection in 7 areas). RESULTS: MR imaging showed 31
      true-positive, 3 true-negative, 4 false-positive and one false-negative diagnosis
      of infection and scintigraphy 27, 7, 0 and 5 respectively. The sensitivity of MR
      for osteomyelitis was 100% (12/12) and of scintigraphy 42% (5/12), p<0.01. The
      specificity of MR and of scintigraphy for osteomyelitis were 81% (22/27) and 93%
      (25/27) respectively. The sensitivity of MR for soft-tissue infection was 96%
      (26/27) and specificity 75% (9/12). The correspoding figures for scintigraphy
      were 85% (23/27) and 100% (12/12). MR and scintigraphy were concordant with
      respect to the final diagnosis in 28/39 (72%) sites and discordant in 10 (26%).
      In one patient with Charcot osteoarthropathy a false-positive finding was found
      by both methods. MR detected all 3 cases of spondylitis, scintigraphy none.
      Nonpyogenic inflammations and neuroarthropathic joints were indistinguishable
      from infection by MR. CONCLUSION: Combined imaging with MR and 99mTc-labeled
      leukocytes is recommended in diagnostically complicated bone infections except
      for spondylitis where MR is the method of choice. Congruent positive findings are
      highly suggestive of infection, the extent of which can be determined. Congruent
      negative results exclude infection.

PMID- 8995458
TI  - Gadolinium-DTPA-enhanced MR imaging in asymptomatic knees.
AB  - PURPOSE: To evaluate the occurrence and extent of Gd-DTPA-enhanced synovial
      structures in asymptomatic knee joints of middle-aged healthy individuals.
      MATERIAL AND METHODS: MR imaging of the knee joint was performed in 10 healthy
      subjects aged 40-61 years. The study included a sagittal T1-weighted SE sequence
      before and after i.v. injection of 0.1 mmol Gd-DTPA/kg b.w. RESULTS: Contrast
      enhanced synovial structures were found in all knees. The extent of the synovial
      structures was usually not uniform within the examined joint. In the
      intercondylar fossa, the thickness of synovial structures was more often
      pronounced. In the suprapatellar recess, synovial thickness was constant and
      minimal. CONCLUSION: The presence and the varying extent and thickness of
      synovial structures in asymptomatic knees in middle-aged individuals must be
      considered in the evaluation of early and mild synovitis of the knee joint with
      Gd-enhanced MR imaging in this age group.

PMID- 8995459
TI  - Imaging approach to the diagnosis of pulmonary sequestration.
AB  - PURPOSE: To describe the characteristic features of pulmonary sequestration (PS),
      to evaluate the usefulness of various imaging modalities, and to find a rational
      approach to accurate diagnosis. MATERIAL AND METHODS: Twenty-four patients with
      PS proved by operation and pathology were reviewed retrospectively. Plain chest
      films were done in all patients, bronchography in 3, sonography in 14, CT in 6
      (including CT angiography in 1 case), MR in 8 (including MR angiography in 1
      case) and aortography in 12 (including DSA in 1 case). RESULTS: Plain chest films
      demonstrated a solid mass in 14 patients and a cystic mass in 10. Bronchograms
      showed displacement of adjacent bronchi with no filling of contrast medium within
      the lesion in 2 cases, while another case had a blind intermediate portion of the
      right bronchus (hypoplasia of middle and lower lobes associated with extralobar
      sequestration). Sonography demonstrated a solid lung mass in 12 cases and a solid
      mass with cystic areas in 2, and detected vessel-like structures within the mass
      or in its surroundings in 12. Doppler analysis showed arterial spectral wave
      confirming a feeding artery. CT revealed a solid mass in all patients, a mass
      with low density area in 4, and emphysema surrounding the mass in 3. MR imaging
      depicted anomalous arteries in all patients and venous drainage in 4 cases.
      Aortography demonstrated anomalous systemic arterial supply to the PS in all
      patients. In this series, 21 cases (87.5%) were correctly diagnosed
      preoperatively by the imaging modalities. CONCLUSION: Plain chest films can
      provide a diagnostic clue to PS. Sonography, CT and MR are helpful for showing
      arterial blood supply and for making a definite diagnosis. We recommend a
      rational imaging approach for the diagnosis of PS.

PMID- 8995460
TI  - Crescentic and ring-shaped opacities. CT features in two cases of bronchiolitis
      obliterans organizing pneumonia (BOOP).
AB  - Two cases of idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) with
      unusual CT findings are presented. On CT both cases exhibited crescentic and ring
      shaped opacities, surrounding areas of groundglass attenuation, and associated
      with a nodular pattern in one patient and airspace consolidations in the second
      patient. CT-pathologic correlation disclosed that the central areas of
      groundglass attenuation corresponded to alveolar septal inflammation, in contrast
      to the denser periphery where granulomatous tissue in peripheral airspaces
      predominated. In the broad spectrum of CT findings, BOOP can exhibit specific CT
      features with regard to the crescentic or ring-shaped opacities with a central
      groundglass attenuation area. Since these features have not been described in any
      other disease, they might be characteristic features for the diagnosis of BOOP.

PMID- 8995461
TI  - Spindle cell lipoma of the breast. A case report.
AB  - A case of spindle cell lipoma of the breast found on mammography in a 53-year-old
      woman is presented. This rare type of tumor has been previously reported on only
      after its presentation as a palpable mass. Radiographically it appears as a well
      circumscribed mass. Ultrasonographically it appears as a homogeneously
      hyperechoic nodule. Histologically these lesions are composed of spindle cells
      intermingled with adipocytes.

PMID- 8995462
TI  - Ultrasound-guided fine-needle aspiration cytology of non-palpable supraclavicular
      lymph nodes in sarcoidosis.
AB  - PURPOSE: The aim of this prospective study was to determine the incidence of
      enlarged supraclavicular lymph nodes by US and the diagnostic yield of US-guided
      aspiration cytology in the diagnosis of sarcoidosis. METHODS: During a 54-month
      period, all consecutive patients with a clinical suspicion of sarcoidosis
      underwent supraclavicular US at the Kiljava Hospital, Finland. All patients with
      enlarged supraclavicular lymph nodes underwent US-guided fine-needle aspiration
      biopsy (FNAB) of the lymph node. RESULTS: Of a total of 250 patients, 27 (10.8%)
      had enlarged supraclavicular lymph nodes at US. All these were non-palpable at
      clinical examination. The cytological specimen was quantitatively sufficient in
      25 of the 27 cases (93%). In 22 (88%) of these, the cytological diagnosis was
      granulomatous inflammation suggestive of sarcoidosis. Three aspirates yielded
      reactive hyperplasia and 2 specimens were insufficient. No complications
      occurred. The patients were followed for 2-42 months (mean 19 months), and the
      diagnosis of sarcoidosis was confirmed clinically in all cases. CONCLUSION:
      Supraclavicular US detects non-palpable enlarged lymph nodes in 1/10 of the
      patients with suspected sarcoidosis. In this subgroup of patients, US combined
      with aspiration cytology may give cytological evidence of granulomatous disease
      similar to sarcoidosis and more invasive diagnostic methods can be avoided.

PMID- 8995463
TI  - Microcatheter embolization of arteriovenous fistulas in the subclavian region.
      Report on three cases.
AB  - PURPOSE: The retrospective evaluation is presented of 3 patients treated with
      endovascular embolization of arteriovenous fistulas (AVFs) in the subclavian
      region. MATERIAL AND METHODS: Three patients, 2 women and one man, were treated
      endovascularly in local anesthesia using microcatheters and fibered platinum
      microcoils. Two patients were asymptomatic and one had unexplained chest pain.
      RESULTS: All 3 AVFs were successfully occluded. One coil slipped through the
      fistula into the pulmonary circulation but caused no clinical sequelae.
      CONCLUSION: AVFs in the subclavian region can be treated by using microcatheters
      and fibered platinum microcoils.

PMID- 8995464
TI  - Thyroid ultrasound findings 7 years after the Chernobyl accident. A comparative
      epidemiological study in the Bryansk region of Russia.
AB  - AIMS: The accident at the Chernobyl nuclear power station occurred in April 1986.
      We report on a comparative epidemiological study on thyroid abnormalities in the
      contaminated and uncontaminated populations of the Bryansk region, South-West
      Russia, in 1993, 7 years after the accident. MATERIAL AND METHODS: The study
      material consisted of all inhabitants aged 3-34 years in the contaminated village
      of Mirnyi and in the uncontaminated village of Krasnyi Rog, excluding those who
      had moved to the villages after the accident. The total material comprised 302
      inhabitants in Mirnyi and 200 in Krasnyi Rog. RESULTS: No pathological US
      findings in either village were found in children born after the accident. In the
      age group 0-9 years old at the time of the accident, the prevalence of thyroid
      abnormalities was 8.1% in the contaminated village compared to 1.6% in the
      uncontaminated village. In the age group 10-27 years the corresponding figures
      were 18.8% and 17.7%. Only 55% of the pathological US findings were detected by
      physical palpation. CONCLUSION: The total prevalence of thyroid abnormalities was
      higher among children in the contaminated village. We recommend an active
      screening of young contaminated subjects with US, supplemented with fine needle
      biopsy.

PMID- 8995465
TI  - Wedge-shaped lesion in the liver seen on postoperative CT. Probable
      thromboembolic phenomenon in the portal venous system.
AB  - PURPOSE: To demonstrate CT findings of a wedge-shaped lesion (WSL) in the liver
      following abdominopelvic surgery and to determine the etiology and incidence of
      WSL. MATERIAL AND METHODS: Retrospective review of teaching files in our
      institution revealed 18 cases showing postoperative WSL in the liver. We also
      retrospectively reviewed CT images of the liver in 104 patients with a recent
      history of abdominopelvic surgery performed during a period of 12 months, as well
      as in 102 patients with no history of surgery during the same period to be used
      as control. Three additional patients with WSL were found in the postoperative
      group and none in the control group. Liver CT images from the 21 patients showing
      WSL, along with their clinical data and follow-up CT where available, were
      retrospectively analyzed. RESULTS: I.v. contrast-enhanced CT showed homogeneous
      higher attenuation of WSL than the surrounding liver in all cases; unenhanced CT
      showed low density in 5 patients, isodensity in 7 patients, and high density in 5
      patients as compared with the surrounding liver. Density on unenhanced CT was
      significantly correlated with the presence or grade of fatty liver (p<0.01). In 5
      cases CT demonstrated clots in the portal vein branch within the area of WSL and
      in 2 cases portal perfusion defects were observed on arterial portal CT,
      corresponding to the areas of WSL. Follow-up CT examinations were available on 15
      patients: WSL became less prominent, or atrophic, or showed no change in 10, 2
      and 3 patients respectively. Follow-up CT showed development of liver metastasis
      in only 3 cases. Only 2 of the 21 patients were clinically symptomatic; one had
      postoperative ileus and the other obstructive jaundice. CONCLUSION: Postoperative
      WSL may represent a thromboembolic phenomenon at the peripheral intrahepatic
      branch of the portal venous system during or after abdominopelvic surgery,
      resulting in a compensatory increase in the hepatic arterial flow that appears as
      wedge-shaped enhancement on CT. This is a clinically asymptomatic and uncommon
      phenomenon (occurring in 3% of abdominopelvic surgeries). It is important that
      this phenomenon is not confused with liver metastasis.

PMID- 8995466
TI  - Radiological findings in biliary fistula and gallstone ileus.
AB  - PURPOSE: Biliary fistula and gallstone ileus are rarely found. The diagnosis is
      difficult and may be delayed until operation. We reviewed the radiological
      findings in a retrospective material. MATERIAL AND METHODS: The cases of 16
      patients treated for biliary fistula were analyzed with respect to findings at
      imaging. Ten patients had a spontaneous fistula. Nine of them had an internal
      bilioduodenal fistula and one had an external fistula with stones passing through
      a subcutaneous abscess. Five patients also had gallstone ileus and one patient a
      rare gastric outlet obstruction caused by a gallstone (Bouveret's syndrome). Six
      patients had an iatrogenic fistula. One of them had internal bile ascites and 5
      an external fistula, one of which was a biliocystic fistula resulting from
      attempted hepatic cyst sclerotherapy. RESULTS: Various imaging modalities were
      used and there was often a delay in the diagnosis. Imaging did not show the
      fistula itself in any of the spontaneous cases. However, a nonvisualized or
      shrunken gallbladder seen at US often coexisted in these cases. CT yielded the
      diagnosis in one case of gallstone ileus, and a Gastrografin meal yielded it in
      the case of Bouveret's syndrome. Fistulography and cholangiography provided a
      correct diagnosis of fistula in all cases of iatrogenic biliocutaneous fistulas.
      CONCLUSION: Patients with biliary fistula usually undergo examinations with
      nonspecific results. The imaging findings could be more specific if the
      possibility of this diagnosis were remembered.

PMID- 8995467
TI  - Toxicity of ethanol in low concentrations. Experimental evaluation in cell
      culture.
AB  - PURPOSE: To define the threshold ethanol concentration that is toxic to cultured
      cells. METHODS: Three malignant cell lines and freshly isolated normal rat
      hepatocytes were exposed to 0-50% (vol.) ethanol (concentrations used were 0, 5,
      10, 15, 20, 25, 30, 40 and 50%) on tissue culture plates for 0.25-60 min
      (exposure times used were 0.25, 5, 10, 20, 30, 40 50 and 60 min). Cytotoxicity
      was estimated by trypan blue exclusion test and from 3H-thymidine incorporation.
      RESULTS: All cells were killed by a 15-s exposure to 30-40% ethanol while a
      concentration as low as 15-20% gave a total response after 5-10-min exposures.
      After a one-hour exposure of F9 carcinoma cells and hepatocytes, a total or
      nearly total response was achieved with 10% ethanol. The cytotoxic effect was
      thus dependent both on the exposure time and on the concentration of ethanol.
      There were no significant differences in ethanol tolerance among the cell types.
      CONCLUSION: Ethanol seemed to kill cells in the cell culture effectively in much
      lower concentrations than those currently used in tumour ablation.

PMID- 8995468
TI  - "Aggressive" renal angiomyolipoma.
AB  - PURPOSE: We describe the US and CT examinations of 4 patients with renal
      angiomyolipoma with an "aggressive" appearance, and review the literature.
      MATERIAL AND METHODS: The imaging findings in 4 patients with benign renal
      angiomyolipomas associated with thrombosis of the renal vein and/or inferior vena
      cava are presented. In one case, enlarged lymph nodes at the renal hilum were
      found. RESULTS: CT demonstrated fat densities within both tumor and thrombus. In
      one patient, small lymph nodes with low density internal areas were detected in
      the para-aortic region. When considering our patients together with those
      reported in the literature, we found that most angiomyolipomas with venous
      invasion were large and centrally located within the kidney. Venous thrombosis
      was observed in 9 lesions of the right kidney, and in only 4 of the left one;
      detection of the site of origin was impossible in one case. One patient only had
      symptoms due to the thrombus; 10 had problems due to the tumor; and 3 were
      asymptomatic. Only 4 patients with pararenal enlarged lymph nodes have been
      reported on in the imaging literature. Fat-containing nodes were detected by CT
      in one case only; the others had enlarged nodes of soft-tissue density. In one
      patient the diagnosis of hamartomatous lymph node invasion was established by
      angiography. CONCLUSION: In patients with renal angiomyolipoma, demonstration of
      both fatty thrombus and the fatty infiltration of lymph nodes of the renal hilum
      cannot be regarded as an indication of malignancy, but only of local aggressive
      behavior. Although surgery is commonly contemplated to prevent symptoms from
      venous thrombosis, conservative treatment seems possible. Detection of enlarged
      lymph nodes of soft tissue density may cause difficult diagnostic problems, with
      the diagnosis addressed only by the presence of associated lesions. Increased
      awareness that renal angiomyolipoma can sometimes appear "aggressive" could help
      to prevent such lesions from being considered malignant, and thus avoid surgical
      confirmation of their nature.

PMID- 8995469
TI  - Effect of transurethral microwave thermotherapy. An evaluation with MR imaging.
AB  - PURPOSE: To detect morphological changes in the prostate, as depicted with MR
      imaging, in order to clarify the effects of transurethral microwave thermotherapy
      (TUMT). MATERIAL AND METHODS: Twenty patients with prostatism and a prostatic
      volume of 30-71 cm3 underwent MR examination before, the day after, and 6 months
      after treatment. TUMT was carried out with a Prostatron. A method to detect
      oedematous changes on heavily T2-weighted MR images was developed and used as an
      indicator of morphological changes. RESULTS: The study showed some correlation
      (r=0.59) between the energy given at TUMT and an increased T2 signal. All
      patients with increased T2 signal except one were found among those who received
      the highest amount of energy to the prostate. Of 8 patients, 6 showed a
      symptomatic response to the treatment and 2 did not. There was a weak statistical
      correlation (r=0.41) between treatment response and increased T2 signal.
      CONCLUSION: The study does not support the view that TUMT leads to significant
      necrosis in the prostate with loss of tissue and retraction. We theorize that the
      response to TUMT may be caused by a denervation of the prostate.

PMID- 8995470
TI  - Primary intraosseous meningiomas.
AB  - PURPOSE: A retrospective study was performed to evaluate the clinical,
      radiological and histological findings of 14 intraosseous meningiomas. MATERIAL
      AND METHODS: 14 histologically proved intraosseous meningiomas were studied with
      plain skull film and CT. Pathological records were reviewed. RESULTS: We found 9
      calvarial cases and 5 spheno-orbital ones. The most common symptom in the
      calvarial cases was a lump in the scalp, and in the spheno-orbital lesions it was
      exophtalmos. Hyperostosis was present in all 5 spheno-orbital cases and in 3 out
      of the 9 calvarial ones; in the other 6 cases it had a mixed pattern. Enhanced
      dura was present in 3 calvarial cases and in 2 sphenoidal ones. Dura was involved
      in 5 cases: 2 with inflammatory changes, 2 with a minimal intradural tumour and
      one with a subdural tumour. CONCLUSION: CT better detected both the bony reaction
      and the intraosseous extension of the tumour. The dural changes were not specific
      of tumoural involvement. The differential diagnosis comprises: fibrous dysplasia,
      osteoma, blastic metastasis and mainly meningioma en plaque (MEP). Comparing our
      findings with other series, we noticed that in some cases the term MEP was used
      for similar cases. As the name MEP is merely descriptive and both entities share
      a larger number of similarities than differences, we believe that a
      differentiation between hyperostotic en plaque meningioma and intraosseous
      meningioma can hardly be made.

PMID- 8995471
TI  - Comparison between conventional and fast spin-echo stir sequences.
AB  - PURPOSE: To evaluate the common characteristics and differences in contrast
      behavior of short-TI-inversion-recovery (STIR) and short-TI-inversion-recovery
      fast spin-echo (TurboSTIR) sequences. MATERIAL AND METHODS: Phantoms doped with
      increasing doses of Gd-DTPA and a pork-fat phantom were used to evaluate the
      dependence of the STIR and TurboSTIR signals on the T1 relaxation time. Clinical
      TurboSTIR images were obtained from 30 patients with musculoskeletal
      abnormalities and compared to conventional STIR images in 15 cases and to
      postcontrast TurboSTIR images in another 15 cases. RESULTS: In the phantom
      measurements, a significantly shorter inversion time (TI) was needed to achieve
      fat suppression on TurboSTIR images, and, with an identical number of signal
      averages, contrast-to-noise ratios were lower on TurboSTIR images. These
      differences between STIR and TurboSTIR can be attributed to the contribution of
      stimulated echoes to overall TurboSTIR signal and can be compensated by a shorter
      TI and a higher number of signal averages for TurboSTIR, respectively. With these
      adaptations, clinical TurboSTIR and STIR images showed an identical contrast
      behavior with fat suppression and a high sensitivity to pathological lesions but
      TurboSTIR saved a significant amount of scan time and reduced some types of
      artifacts. Contrast uptake impaired lesion conspicuity on TurboSTIR images.
      CONCLUSION: TurboSTIR sequences should replace conventional STIR sequences and
      should be performed before contrast administration.

PMID- 8995472
TI  - Effects of the low-osmolality contrast medium ioversol (Optiray) on renal
      function in a geriatric population.
AB  - PURPOSE: To assess the incidence of nephrotoxicity following i.v. injection of
      the iodinated low-osmolality contrast medium ioversol 300 (Optiray) in a
      geriatric population compared with a control group aged under 60 years, neither
      group presenting any associated risk factors. MATERIAL AND METHODS: CT with i.v.
      bolus injection of ioversol 300 mg I/ml was performed at a mean dose of 1.36+/
      0.06 ml/kg (range 1-2 ml/kg b.w.) in 47 patients aged over 69 years. Serum
      creatinine level was measured and creatinine clearance was calculated at 24, 48
      and 72 h after the examination, and compared to a reference serum creatinine
      value taken before CT. The findings were compared with a control group of 44
      patients aged under 60 years. RESULTS: No significant increase in serum
      creatinine (+0.6 mmol/l) or in creatinine clearance (+0.7 ml/min) was found
      during the course of 3 days after the injection. Only one patient (aged 82)
      presented an increase of 25% in serum creatinine (109 mmol/l). CONCLUSION: The
      trial did not demonstrate any significant difference between the 2 groups,
      although the elderly patients had a subclinical renal impairment revealed by the
      decrease of the initial creatinine clearance. The use of low-osmolality ioversol
      makes it possible to perform examination with an iodinated contrast agent without
      increasing the incidence of nephrotoxicity in elderly subjects.

PMID- 8995473
TI  - Effects of ionic and nonionic contrast media on endothelium and on arterial
      thrombus formation.
AB  - BACKGROUND: The aims of the present study were to investigate whether ionic and
      nonionic contrast media (CM) affect: 1) the procoagulant and fibrinolytic
      activities of cultured human vessel endothelium; and 2) early events of tissue
      factor-induced arterial thrombus formation under conditions which may follow a
      percutaneous transluminal coronary angioplasty (PTCA) procedure. The following 3
      CM were studied: iohexol (nonionic monomer, Omnipaque); iodixanol (nonionic
      dimer, Visipaque); and ioxaglate (ionic dimer, Hexabrix). Saline (0.9%) and
      glucose (40 vol%) were used as control. METHODS AND RESULTS: Exposing endothelium
      to 40 vol% CM for 10 min did not affect the selected parameters of cellular
      procoagulant (tissue factor), anticoagulant (thrombomodulin), fibrinolytic
      (tissue plasminogen activator) or antifibrinolytic (plasminogen activator
      inhibitor-1) activity or antigen. However, ioxaglate had a profound impact on the
      cell morphology, which was noted already after one minute of exposure. The cells
      contracted and rounded, exposing large areas of extracellular matrix. Iohexol
      showed this phenomenon to a considerably lesser extent, whereas iodixanol induced
      a slight swelling of the cells without detectable exposure of extracellular
      matrix. The effect of the respective CM on tissue-factor-driven thrombus
      formation at an arterial shear rate of 2600 s-1 was studied in an ex vivo
      parallel-plate perfusion chamber device. In this model, human native blood was
      passed over a tissue factor/phospholipid-rich surface following 30 s exposure to
      100% CM. The CM was washed out by nonanticoagulated blood drawn directly from an
      antecubital vein by a pump positioned distal to the perfusion chamber. Such a pre
      exposure of the procoagulant surface to iodixanol reduced the fibrin deposition
      around the platelet thrombi by 50% (p<0.01). However, iohexol and ioxaglate did
      not affect fibrin deposition. None of the 3 CM affected the recruitment of
      platelets in the thrombi, since similar values were obtained with pre-exposure to
      40 vol% of saline. CONCLUSION: Iodixanol appears to be most biocompatible with
      endothelium, and has a moderate inhibitory effect on fibrin deposition in flowing
      blood. This differs from iohexol, and in particular from ioxaglate, which induce
      endothelial changes in morphology with no effect on fibrin deposition. Since none
      of the CM affected the platelet aggregate formation, and since ioxaglate has been
      reported to have stronger anticoagulant and antithrombotic properties than
      iodixanol or iohexol in in vitro assays, it is apparent that these properties
      were not reflected in thrombus formation under the experimental conditions of
      high arterial shear.

PMID- 8995475
TI  - Elimination of low-osmolality contrast media by hemodialysis.
AB  - PURPOSE: To compare the dialyzability and safety of 2 types of low-osmolality
      contrast media administered to end-stage renal failure patients maintained on
      regular hemodialysis. MATERIAL AND METHODS: Of 44 CT examinations, iohexol was
      used in 22 and ioxaglate in the other 22. Adverse reactions and hemodynamic
      changes were recorded. Thirty minutes after the beginning of CT investigation,
      hemodialysis was commenced. Elimination rate and clearance of the contrast media
      were measured as indices of their dialyzability. RESULTS: After 4 hours of
      hemodialysis, 78.4+/-6.5% of iohexol and 72.4+/-6.0% ioxaglate were eliminated.
      Clearance of iohexol was higher than that of ioxaglate at all sampling times. No
      severe hemodynamic change nor adverse reaction were observed. Minor reactions
      were more frequently observed in the ioxaglate group. CONCLUSION: Iohexol, a
      nonionic monomeric contrast medium, is more advantageous for hemodialysis
      patients than ioxaglate, an ionic dimeric contrast medium.

PMID- 8995474
TI  - Effect of iomeprol on renal function immediately after abdominal angiography.
AB  - PURPOSE: To investigate the acute renal effects of 2 osmolality levels of
      iomeprol in a double-blind, randomized, parallel-group study. MATERIAL AND
      METHODS: Ten patients received iomeprol 300 mg I/ml, and a further 10 received
      iomeprol 400 mg I/ml intraarterially at routine abdominal angiography. The mean
      volume of contrast medium administered was 227.3+/-59.3 ml in the iomeprol 300
      group and 221.5+/-30.9 ml in the iomeprol 400 group. RESULTS: The urinary minute
      volume increased immediately after angiography, but tended to return to baseline
      120 min after the examination. No significant decrease in creatinine clearance
      occurred; however, the fraction excretion of sodium increased immediately after
      angiography. The lysosomal enzyme N-acetyl-beta-glucosaminidase and the proximal
      tubular brush border enzyme gamma-glutamyl transferase increased up to 120 min
      after the procedure. Free water clearance was negative during each study period.
      No statistical differences in any parameter were evident between these 2 groups.
      CONCLUSION: These results suggest that osmotic diuresis and its acute effect on
      proximal tubular function are induced by the administration of iomeprol, but that
      these changes are reversible.

PMID- 8995476
TI  - MR imaging of edematous limbs.

PMID- 8995477
TI  - Molecular cloning of the papillary renal cell carcinoma-associated translocation
      (X;1)(p11;q21) breakpoint.
AB  - A combination of Southern blot analysis on a panel of tumor-derived somatic cell
      hybrids and fluorescence in situ hybridization techniques was used to map YACs,
      cosmids and DNA markers from the Xp11.2 region relative to the X chromosome
      breakpoint of the renal cell carcinoma-associated t(X;1)(p11;q21). The position
      of the breakpoint could be determined as follows: Xcen-OATL2-DXS146-DXS255-SYP
      t(X;1)-TFE 3-OATL1-Xpter. Fluorescence in situ hybridization experiments using
      TFE3-containing YACs and cosmids revealed split signals indicating that the
      corresponding DNA inserts span the breakpoint region. Subsequent Southern blot
      analysis showed that a 2.3-kb EcoRI fragment which is present in all TFE3 cosmids
      identified, hybridizes to aberrant restriction fragments in three independent
      t(X;1)-positive renal cell carcinoma DNAs. The breakpoints in these tumors are
      not the same, but map within a region of approximately 6.5 kb. Through
      preparative gel electrophoresis an (X;1) chimaeric 4.4-kb EcoRI fragment could be
      isolated which encompasses the breakpoint region present on der(X). Preliminary
      characterization of this fragment revealed the presence of a 150-bp region with a
      strong homology to the 5' end of the mouse TFE3 cDNA in the X-chromosome part,
      and a 48-bp segment in the chromosome 1-derived part identical to the 5' end of a
      known EST (accession number R93849). These observations suggest that a fusion
      gene is formed between the two corresponding genes in t(X;1)(p11;q21)-positive
      papillary renal cell carcinomas.

PMID- 8995478
TI  - Mapping of the genetically independent chicken major histocompatibility complexes
      B@ and RFP-Y@ to the same microchromosome by two-color fluorescent in situ
      hybridization.
AB  - The chicken MHC is organized in two genetically independent gene complexes B@ and
      RFP-Y@. Previous studies have shown the localization of the B@ complex on a small
      microchromosome. By using two-color fluorescent in situ hybridization, we
      demonstrate the localization of the RFP-Y@ complex to the same chromosome. A
      recombination hot spot between the two loci might account for their independent
      segregation.

PMID- 8995479
TI  - High-resolution FISH mapping of beta-defensin genes to river buffalo and sheep
      chromosomes suggests a chromosome discrepancy in ffttle standard karyotypes.
AB  - High-resolution chromosomal fluorescence in situ hybridization (FISH) and R
      banding allowed the chromosomal localization of the beta-defensin gene cluster
      (DEFB@) to chromosome band 1p12 in the river buffalo (Bubalus bubalis, 2n = 50)
      and to band 24q13 in sheep (Ovis aries, 2n = 54), according to standard
      nomenclatures. The localizations permitted the tentative assignment of the entire
      bovine syntenic group U25 to these chromosomes. A FISH mapping control on cattle
      chromosomes confirmed the localization of DEFB@ in the homoeologous chromosome
      and chromosome band. Comparisons were made between river buffalo chromosome 1p
      and the homoeologous cattle chromosome on standard karyotypes; the results are
      discussed in light of gene assignments, extensive chromosome band conservation
      among the Bovidae, and inconsistencies in domestic cattle chromosome
      nomenclatures.

PMID- 8995480
TI  - Genetic mapping of GLCLC, the human gene encoding the catalytic subunit of gamma
      glutamyl-cysteine synthetase, to chromosome band 6p12 and characterization of a
      polymorphic trinucleotide repeat within its 5' untranslated region.
AB  - The first and rate-limiting step in the formation of glutathione is catalyzed by
      gamma-glutamylcysteine synthetase (glutamate-cysteine ligase, E.C. 6.3.2.2).
      Herein, we describe a trinucleotide repeat polymorphism located in the 5'
      untranslated region of the human gene, GLCLC, that encodes the catalytic subunit
      of this enzyme, and we genetically map GLCLC to band 6p12, 1.6 cM distal to
      D6S295.

PMID- 8995481
TI  - Chromosome imbalances in papillary renal cell carcinoma and first cytogenetic
      data of familial cases analyzed by comparative genomic hybridization.
AB  - We used comparative genomic hybridization to analyze 17 tumor samples from 11
      patients with papillary renal cell carcinoma (RCC), including three patients with
      hereditary papillary RCC. Whereas the most frequent aberrations confirmed data
      obtained by banding analyses, copy number increases on 5q, which previously were
      considered characteristic of nonpapillary RCC, were identified in two cases. In
      two complex cases belonging to the same family, a characteristic pattern of
      chromosomal aberrations was found: five of the six imbalances present in the less
      complex case were included in the karyotype of the other case, suggesting a
      genetically determined mechanism resulting in genomic instability of specific
      chromosomes or chromosomal subregions and/or selection of specific mutations.

PMID- 8995483
TI  - Cloning of the bovine activin receptor type II gene (ACVR2) and mapping to
      chromosome 2 (BTA2).
AB  - The cDNA for the bovine activin receptor type II (ACVR2) gene has been cloned and
      sequenced. It encodes a protein of 513 amino acids which is highly homologous
      (approximately 98% identity) to the human, mouse, and rat proteins. Using PCR
      analysis of bovine x hamster somatic cell lines, the ACVR2 gene was mapped to
      syntenic group U17, which has been localised to bovine chromosome 2. Comparative
      mapping has shown that the genes within U17 are also in a syntenic group on the
      long arm of human and sheep chromosome 2, as well as on mouse chromosome 1. This
      group of genes represents an evolutionarily conserved mammalian chromosomal
      segment. Genotyping a highly polymorphic microsatellite locus, (AT)4(GT)9(AT)11,
      found within an intron of this gene confirmed the localisation by linking the
      ACVR2-associated microsatellite to the region of chromosome 2 flanked by CSSM42
      and TGLA226. This gene locus, which has the characteristics of a type I and type
      II mapping locus, represents the first localisation of this gene in any species
      to date.

PMID- 8995482
TI  - Comparative mapping of Na+-phosphate cotransporter genes, NPT1 and NPT2, in human
      and rabbit.
AB  - The chromosome locations of the rabbit (Oryctolagus cuniculus) Na+-phosphate
      cotransporter genes NPT1 and NPT2 were determined by fluorescence in situ
      hybridization. Our results localize NPT1 to rabbit chromosome 12p11 and NPT2 to
      rabbit chromosome 3p11. The corresponding genes in the human map to chromosome
      bands 6p22 and 5q35, respectively. These assignments agree with the previously
      reported homology between rabbit chromosome 12 and human chromosome 6 and provide
      the basis for the establishment of a conserved syntenic group between rabbit
      chromosome 3 and human chromosome 5.

PMID- 8995484
TI  - Assignment of the ATBF1 transcription factor gene (Atbf1) to mouse chromosome
      band 8E1 by in situ hybridization.

PMID- 8995485
TI  - Chromosome homology between the domestic pig and the babirusa (family Suidae)
      elucidated with the use of porcine painting probes.
AB  - Homology among three pairs of domestic pig (Sus scrofa) and five pairs of
      babirusa (Babyrousa babyrussa) autosomes has been demonstrated with the use of
      porcine painting probes. With the results of this study, in addition to data
      obtained earlier through the application of banding techniques, correspondence
      between all individual chromosomes of these two distantly related pigs has been
      identified.

PMID- 8995486
TI  - Assignment of the human slow twitch skeletal muscle/cardiac troponin C gene
      (TNNC1) to human chromosome 3p21.3-->3p14.3 using somatic cell hybrids.

PMID- 8995487
TI  - Identification and chromosome mapping of the mouse homologue of the human gene
      (DDX6) that encodes a putative RNA helicase of the DEAD box protein family.
AB  - The human DDX6 gene (alias RCK) at chromosome 11 band q23 was identified through
      the study of the breakpoint of t(11;14)(q23;q32) translocation in a B-cell
      lymphoma cell line, RC-K8. DDX6 encodes a DEAD box protein/RNA helicase. Positive
      mouse genomic and cDNA recombinant clones were obtained by screening mouse B-cell
      genomic and cDNA libraries with a human DDX6 cDNA probe. The deduced amino acid
      sequence of an open reading frame from a cDNA clone revealed a protein with 92.5%
      identity to human ddx6/p54. All positive mouse genomic recombinant clones, and
      cDNA clones containing mouse Ddx6 (previous gene symbol: Rck), were localized by
      fluorescent in situ hybridization to band B of mouse Chromosome 9, a region
      showing conserved linkage homology to human chromosome 11 band q23. Mouse Ddx6
      was localized to the region between Ncam and D9Mit45 by molecular linkage
      analysis. A 7.5-kb mRNA and a 54-kDa protein were identified as mouse Ddx6 gene
      products which are similar in size to products of the human DDX6 gene, as shown
      by Northern and Western blot analyses.

PMID- 8995488
TI  - A finding of the XX/XY1Y2 sex-chromosome system in Taterillus arenarius
      (Gerbillinae, Rodentia) and its phylogenetic implications.
AB  - A chromosome banding study (R- and C-bands) of a male Taterillus arenarius
      (Rodentia, Gerbillinae) specimen from Mauritania revealed the presence of an
      XX/XY1Y2 sex-chromosome system in the karyotype, as found previously in three
      other congeneric species. This finding allowed us to resolve the phylogenetic
      affinities of this species within the genus and to propose an evolutionary
      scenario leading to the formation of the species with an XX/XY1Y2 sex-chromosome
      system. A review of chromosome data in Taterillus suggests that there may be more
      species in the genus than hitherto recognized.

PMID- 8995490
TI  - Development of DNA libraries specific for Chinese hamster chromosomes 3, 4, 9,
      10, X, and Y by DOP-PCR.
AB  - In a previous study of ours, DNA libraries specific for Chinese hamster
      chromosomes 1, 2, 3, 5, 6, 7, and 8 were constructed by single laser flow sorting
      and the linker adapter PCR method. Since a single laser flow sorting of
      chromosomes is based on chromosome size, it is difficult to separate chromosomes
      of equal size, such as chromosome 3 and the X chromosome. This problem can be
      circumvented by bivariate flow sorting. In the present study, we have used
      bivariate flow sorting of Chinese hamster chromosomes and the degenerate
      oligonucleotide-primed polymerase chain reaction (DOP-PCR) for generating DNA
      libraries specifically for chromosomes 3, 4, 9, 10, X, and Y. Fluorescence in
      situ hybridization (FISH) analyses indicate that the probe libraries are highly
      specific and can be applied to various cytogenetic studies.

PMID- 8995489
TI  - Molecular characterization of the complex sex-chromosome heterochromatin in the
      rodent Microtus chrotorrhinus.
AB  - The sex chromosomes of Microtus chrotorrhinus are unusually large compared to
      those of other mammals, comprising about 20% of the karyotype and containing
      substantial amounts of constitutive heterochromatin. Previous studies have
      described two highly repeated DNA families (MSAT-160 and MSAT-2570) that localize
      to this heterochromatin (Modi, 1992, 1993c). The present report describes a third
      satellite DNA family (termed MSAT-21) in M. chrotorrhinus that is also located in
      the sex heterochromatin. This repeat consists of diverged copies (average
      similarity = 75%) of a tandemly repeated 21-mer. Southern blotting of MSAT-21
      revealed that although some higher order (5-20 kb) repeats do exist, none has
      spread throughout an appreciable portion of the genome. Pulsed field gel
      experiments indicated that most of the larger arrays (50-700 kb) of all three
      satellite families are distributed across numerous size classes, suggesting that
      the three repeats are interspersed with one another in this heterochromatin.
      Analysis of a boundary between MSAT-21 and MSAT-160 showed that the junction
      monomers of each satellite are intact and that a pentanucleotide has apparently
      been transferred from MSAT-21 to MSAT-160 via recombination. Sequence comparisons
      of MSAT-160 with another rodent satellite and with the U3 region of the Rous
      sarcoma virus (RSV) long terminal repeat identified inverted repeats and
      similarities with viral enhancer domains in the rodent sequences. Additionally,
      the MSAT-21 consensus was found to be similar to the R region of RSV, suggesting
      a retroviral ancestor for these rodent repeated DNA families.

PMID- 8995491
TI  - Generation of mouse chromosome painting probes by DOP-PCR amplification of
      microdissected meiotic chromosomes.
AB  - We describe here the development of four sets of painting probes for mouse
      chromosomes 1 and 13, 2 and 8, 6 and 15, and X and Y by degenerate
      oligonucleotide-primed polymerase chain reaction (DOP-PCR) amplification of 10-20
      copies of microdissected male meiotic chromosomes. The X,Y probe was obtained
      from the X-Y bivalent of diakinesis/metaphase I complements of mice with a normal
      karyotype, whereas the other probes were derived from tri- or quadrivalents in
      diakinesis/metaphase I of two reciprocal translocations, T(1;13)70H and
      T(2;8)2Wa, and one inversion heterozygote carrying a small deletion,
      In(6;15)Rb1Ald del6(15)1Wa. The specificity of these probes was established by
      fluorescence in situ hybridization (FISH) to meiotic and mitotic metaphase
      complements. The chromosomes painted by these probes could be identified by
      single or multicolor FISH.

PMID- 8995492
TI  - Alterations of yeast artificial chromosome transgenic sequences in stretched
      embryonic stem-cell chromatin visualized by fluorescence in situ hybridization.
AB  - Transgenic mice have been generated from embryonic stem (ES) cells carrying
      functional genes cloned within yeast artificial chromosomes (YACs). Information
      on the integrity and organization of the inserted sequences, including the number
      of copies and their orientation to each other, is still limited by current
      methods. We have applied fluorescence in situ hybridization to stretched
      chromatin preparations from YAC-transfected ES cells to analyze the organization
      and copy number of the integrated sequences.

PMID- 8995493
TI  - A phase I/II study of continuous infusion suramin in patients with hormone
      refractory prostate cancer: toxicity and response.
AB  - INTRODUCTION: Suramin is a synthetic polysulfonated naphthylurea which has been
      used for the treatment of African trypanosomiasis and onchocerciasis, but since
      the mid-1980s has received attention as a possible antiretroviral and
      antineoplastic agent. OBJECTIVE: This clinical trial of suramin was undertaken as
      a phase I/II study in patients with hormone-refractory prostate cancer, with the
      hypothesis that the intensity of therapy with suramin could be increased
      significantly if measures were undertaken to maintain the plasma concentrations
      of the drug under 300 microg/ml. METHODS: We report the clinical results of this
      trial, wherein patients were treated at three different targeted plasma suramin
      concentrations (275, 215 and 175 microg/ml) for varying periods of time (2, 4 or
      8 weeks), with delivery of the drug by continuous intravenous infusion. RESULTS:
      The major toxicity observed in this trial was neurologic, consisting of a motor
      and sensory peripheral neuropathy that resulted in both paresis and paralysis of
      the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was
      observed in the patients treated at a plasma suramin concentration of 275
      microg/ml for 4 or more weeks. A single patient treated at 215 microg/ml for 8
      weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and
      no patient treated at 175 microg/ml developed this toxicity. The second most
      common toxicity observed was infection of the central venous catheter. The
      overall response rate for all of the evaluable patients was 17% (13 of 75
      patients). In addition, prostate-specific antigen (PSA)-defined responses were
      observed in six patients receiving therapy at 175 microg/ml, but these responses
      were confounded by cessation of therapy with flutamide during suramin treatment.
      CONCLUSIONS: In summary, although plasma suramin concentrations were maintained
      below 300 microg/ml, neurologic toxicity nonetheless occurred with high frequency
      in patients treated at 275 microg/ml for 4 or more weeks. Therapy at 215 and 175
      microg/ml was in general well tolerated, but central venous catheter-related
      infection, as well as the inconvenience and expense of continuous infusional
      therapy, make this method of drug delivery impractical. Only moderate antitumor
      activity was observed during this trial, but it is possible that both
      continuation of flutamide and flutamide withdrawal during suramin therapy
      confounded the assessment of suramin's activity in hormone-refractory prostate
      cancer.

PMID- 8995494
TI  - The effects of food and divided dosing on the bioavailability of oral
      vinorelbine.
AB  - The effects of food and divided dosing on the bioavailability of a liquid-filled
      gelatin capsule formulation of vinorelbine (Navelbine), a semisynthetic vinca
      alkaloid with broad clinical activity, was evaluated in patients with advanced
      solid tumors. A group of 13 patients were randomized to treatment with the oral
      formulation at the recommended phase II dose of 80 mg/m2 per week either in the
      fasting state or after ingestion of a standard meal. Patients were treated 1 week
      later in the alternate state relative to their first dose. The effects of divided
      dosing were assessed during the 3rd week, at which time vinorelbine was
      administered in two divided doses. After the completion of pharmacokinetic and
      bioavailability studies, patients received the oral formulation at a dose of 80
      mg/m2 per week in two divided doses to evaluate the feasibility of chronic oral
      drug administration. Both manipulations resulted in small, albeit statistically
      significant, reductions in the relative bioavailability of this oral formulation.
      The relative bioavailability decreased by 22 +/- 28% when treatment followed the
      ingestion of a standard meal, possibly due to a delay in gastrointestinal transit
      time. The mean time of maximum plasma concentration (Tmax) increased from 1.3 +/-
      1.6 h in the fasting state to 2.5 +/- 1.6 h in the fed state, although this
      difference was not statistically significant. Similarly, the relative
      bioavailability declined by 16 +/- 51% when vinorelbine was administered in two
      divided doses. An analysis of dose proportionality revealed disproportionate
      increases in dose-normalized Cmax and AUC values with single oral doses above 120
      mg, which may account for this phenomenon. The high clearance of vinorelbine,
      which approaches hepatic blood flow, and the lack of dose proportionality after
      oral administration, indicate that there is a large first-pass effect which may
      be saturable, or nonlinear, above single doses of 120 mg. In addition, the
      toxicological and pharmacological characteristics of oral vinorelbine indicate
      that treatment after a standard meal or on a divided dosing schedule is safe.
      Chronic oral administration of the agent in two divided doses was also well
      tolerated. However, the small reduction in the relative bioavailability following
      the ingestion of a standard meal and with divided dosing suggest the need for
      further pharmacodynamic studies to determine if reductions in drug exposure of
      this magnitude may portend diminished antitumor activity.

PMID- 8995495
TI  - Intraliposomal conversion of lipophilic cis-bis-carboxylato-trans-R,R-1,2
      diaminocyclohexane-platinum (II) complexes into cis-bis-dichloro-trans-R,R-1,2
      diaminocyclohexane-platinum (II).
AB  - Cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (NDDP) is a
      lipophilic platinum complex (Pt complex) developed in a liposomal carrier. Prior
      studies have suggested that NDDP is a prodrug that exerts its biological activity
      through activation within the liposome bilayers containing dimyristoyl
      phosphatidylglycerol (DMPG) before in vivo administration. In order to understand
      the kinetics of the intraliposomal degradation/activation of different liposomal
      Pt complexes, we studied the effects of their structure, lipid composition,
      content of acidic phospholipids and size, and the effects of pH, temperature and
      the presence of residual chloroform on their stability, in vitro cytotoxicity,
      and in vivo antitumor activity. The following factors were found to enhance the
      intraliposomal degradation/activation of Pt complexes: (1) the size and spatial
      configuration of the Pt complex, (2) an acidic pH, (3) a high temperature, (4)
      the presence and amount of acidic phospholipids, and (5) the presence of residual
      chloroform. Liposome size did not affect the intraliposomal stability of
      different Pt complexes. Good inverse relationships between the extent of drug
      degradation and in vitro cytotoxicity and between the extent of drug degradation
      and in vivo antitumor potency were observed, thus confirming that the biological
      activity of these complexes is exerted through the intraliposomal formation of
      certain active intermediate(s). The only active intermediate that could be
      identified was cis-bis-dichloro-trans-R,R-1,2-diaminocyclohexane platinum(II)
      whose structure was confirmed by 1H, 13C, and 195Pt nuclear magnetic resonance
      (NMR) spectroscopy.

PMID- 8995496
TI  - Cisplatin pharmacokinetics and pharmacodynamics in patients with squamous-cell
      carcinoma of the head/neck or esophagus.
AB  - The pharmacokinetics of total platinum (Pt) in plasma and cisplatin (CDDP)-DNA
      adducts in different cell types were described in ten patients with squamous-cell
      carcinoma of the head/neck or esophagus after their first cycle of chemotherapy
      containing a CDDP dose of 100 mg/m2. Nephrotoxicity was studied in terms of
      urinary excretion of marker proteins (protein HC, IgG, and albumin).
      Pharmacodynamic relationships between pharmacokinetic parameters and toxicity
      were investigated. A population-based model with limited sampling was found
      feasible for producing pharmacokinetic information, in accordance with literature
      data. The kinetics of two normal cell types with different turnover (lymphocytes
      and buccal cells) appeared to have different kinetic profiles of CDDP-DNA
      adducts. Analysis of urinary excretion of marker proteins (protein HC, albumin,
      and IgG) showed that the nephrotoxicity was displayed first as tubular damage and
      later as impaired glomerular barrier function. There were indications that
      tubular nephrotoxicity may be predicted by pharmacokinetic parameters of plasma
      Pt. We found older patients to have a lower Pt clearance and more extensive early
      tubular damage. There was no correlation between CDDP-DNA adducts in normal cells
      and nephrotoxicity. Larger studies are warranted to define the pharmacokinetic
      window of CDDP. Limited sampling for analysis of CDDP pharmacokinetics may then
      be a possible avenue for individualizing the dose and, thus, improving the
      clinical use of the drug.

PMID- 8995498
TI  - NONMEM population pharmacokinetic studies of cytosine arabinoside after high-dose
      and after loading bolus followed by continuous infusion of the drug in pediatric
      patients with leukemias.
AB  - We examined the population pharmacokinetics (PPK) of cytosine arabinoside (ara-C)
      after high-dose ara-C (HDara-C) (3 g/m2 every 12 h) and after a loading bolus
      (LB) plus continuous infusion (C1) of ara-C for 72 h in 52 pediatric patients
      with leukemias, enrolled in four clinical trials. The PPK analyses of the drug
      were performed using the NONMEM program. The patients' ages ranged from 2 months
      to 19 years. The ara-C data were analyzed using a two-compartment open model.
      Interindividual variability was described by the constant coefficient of
      variation (CCV) model, while the intraindividual variability was described by a
      combined additive and CCV error model. The covariates age (AGE) and surface area
      (SA) were tested to examine their influence on the estimation of the ara-C PPK
      parameters. In the absence of model covariates, the data fit was characterized by
      considerable bias, as indicated by the plot of measured vs predicted ara-C
      concentrations. The fit of the data was greatly improved when the parameters
      total body clearance (CL), intercompartmental clearance (Q), and volumes of
      distribution of central (Vd1) and peripheral (Vd2) compartments were expressed as
      linear functions of the covariate product, AGE x SA. The final parameter
      estimates were: CL = 2.59 x AGE x SA 1/h, Q = 2.01 x AGE x SA 1/h, Vd1 = 0.48 x
      AGE x SA1, and Vd2 = 38.1 x AGE x SA1. The coefficients of variation of CL, Q,
      Vd1 and Vd2 were 83.79%, 12.08%, 40.0%, and 52.54%, respectively, indicating
      substantial interindividual variability. In separate NONMEM analyses, the PK of
      ara-C and its metabolite uracil arabinoside (ara-U) were modeled simultaneously
      in order to investigate whether the dependence of ara-C on patient age was due to
      increased deamination of ara-C to ara-U. The PK of ara-C were described by the
      two-compartment open model while the PK of ara-U were simultaneously described by
      the one-compartment open model. The conversion of ara-C to ara-U was modeled as a
      first-order kinetic process due to the relatively low concentrations of ara-C in
      plasma. These PPK analyses indicated that elimination of ara-C from the central
      compartment occurs primarily by its metabolic conversion to ara-U and that the
      rate of conversion of ara-C to ara-U increases with increasing patient age, which
      explains the higher ratios of ara-U to ara-C and, hence, the increased ara-C
      clearance observed in older children as compared to infants. We conclude that the
      NONMEM PPK methodology allowed the simultaneous analyses of data from different
      doses and dose regimens and explained phenomena that prior standard two-stage
      analyses could not.

PMID- 8995497
TI  - Pharmacokinetic studies of 13-cis-retinoic acid in pediatric patients with
      neuroblastoma following bone marrow transplantation.
AB  - A phase I clinical trial of 13-cis-retinoic acid (cis-RA) was undertaken to
      determine the maximally tolerated dose (MTD) and pharmacokinetics (PK) of cis-RA
      following bone marrow transplantation (BMT) in children with high-risk
      neuroblastoma. Mean peak serum levels of cis-RA in 31 pediatric patients ranged
      from 4.9 to 8.9 microM following doses of 100-200 mg/m2 per day, divided into two
      doses every 12 h administered orally. The PK of cis-RA obeyed a single
      compartment model following first-order absorption in the majority of patients. A
      linear increase in the mean peak serum levels and area under the time
      concentration curve (AUC) with increasing dose was observed. The average half
      lives of absorption and elimination were 1.0 and 5.8 h, respectively. At the MTD
      of 160 mg/m2 per day, the mean cis-RA peak serum concentration was 7.2 +/- 5.3
      microM. AUC values were not altered significantly during a 2-week course of
      treatment or over a long period of multiple courses. Levels of trans-retinoic
      acid, a metabolite of cis-RA, remained low but were similar on days 1 and 14,
      whereas the 4-oxo-13-cis-RA metabolite had increased in 64% of patients by day
      14. Peak serum cis-RA concentrations correlated with clinical toxicity as grade 3
      to 4 toxicity was seen in 44% of patient-courses (8/18) with peak serum levels >
      10 microM, but only 13% (12/96) with peak serum levels < 10 microM. These results
      show that cis-RA given at 160 mg/m2 to children achieved serum concentrations
      known to be effective against neuroblastoma in vitro, and the PK for cis-RA
      differs from that reported for trans-retinoic acid in children.

PMID- 8995499
TI  - Plasma pharmacokinetics, bioavailability, and tissue distribution in CD2F1 mice
      of halomon, an antitumor halogenated monoterpene isolated from the red algae
      Portieria hornemannii.
AB  - The purpose of the present study was to define the plasma pharmacokinetics,
      bioavailability, and tissue distribution in mice of halomon, a halogenated
      monoterpene from Portieria hornemanii that is active in vitro against brain-,
      renal-, and colon-cancer cell lines. Halomon formulated in
      cremophor:ethanol:0.154 M NaCl (1:1:6, by vol.) was injected i.v. at 20, 60, 90,
      or 135 mg/kg into female CD2F1 mice. Doses of 135 mg/kg were also given i.p.,
      s.c., and by enteral gavage to female CD2F1 mice and i.v. to male CD2F1 mice.
      Plasma halomon concentrations were measured with a gas-chromatography system
      using electron-capture detection. Halomon concentrations were also determined in
      the brains, hearts, lungs, livers, kidneys, spleens, skeletal muscles, fat, red
      blood cells, and, if present, testes of mice given 135 mg/kg i.v. Halomon plasma
      pharmacokinetics were well fit by a two-compartment, open linear model and were
      linear between 20 and 135 mg/kg. Population estimates of parameters describing
      halomon plasma pharmacokinetics in female CD2F1 mice were developed with a
      standard two-stage technique and also by simultaneous modeling of data from 20-,
      60-, 90-, and 135-mg/kg i.v. studies in female mice. Halomon bioavailability was
      45%, 47%, and 4% after i.p., s.c., and enteral dosing, respectively. Urinary
      excretion of the parent compound was minimal. Halomon was distributed widely to
      all tissues studied but was concentrated and persisted in fat. Halomon
      concentrations measured in the brain were comparable with concomitant
      concentrations detected in plasma and most other tissues. These data and models
      are helpful in the simulation and evaluation of conditions produced by
      preclinical screening and toxicology studies.

PMID- 8995500
TI  - Pharmacodynamic modeling of prolonged administration of etoposide.
AB  - PURPOSE: A refined pharmacodynamic model for toxicity is necessary for successful
      adaptive control of the administration of an anticancer drug to avoid toxicity.
      We sought to establish a pharmacodynamic model of leukopenia in a 14-day
      administration of etoposide. METHODS: Pharmacokinetic data of 32 patients treated
      with etoposide infused over 14 days in a phase I study (20 patients) or in an
      adaptive control study (12 patients) were used to develop a model for the
      prediction of a leukocyte nadir count. The concentrations of both estimated
      unbound and total etoposide at steady state, as well as patient demographic
      factors, were included in linear and nonlinear models. The unbound fraction of
      etoposide was estimated using an equation based on serum albumin and total
      bilirubin. The efficacy of the models was evaluated in terms of correlation
      coefficient (r), mean predictive error (MPE) and root mean square error (RMSE).
      RESULTS: For both total and unbound drug concentration, a nonlinear model
      predicted leukopenia more precisely and with less bias than a linear model, and
      unbound drug explained more variability of leukopenia than total drug
      concentration in both linear and nonlinear models. The best model was a nonlinear
      model with three variables of unbound concentration, pretreatment leukocyte count
      and prior treatment (r = 0.76, MPE +/- SEM = 0.07 +/- 0.17 x 10(3)/microl, RMSE =
      0.95 x 10(3) microl), which was better than the best linear model. CONCLUSIONS:
      The nonlinear model using unbound etoposide concentration explained the
      interpatient variability of leukocyte nadir count to a fairly large extent.
      Although the model provided useful information on the pharmacodynamics of
      etoposide, it was still imprecise and a more refined model is necessary for
      application to an adaptive control study.

PMID- 8995501
TI  - Electropermeabilization in bladder cancer chemotherapy.
AB  - PURPOSE: Electropermeabilization has been used for the introduction of genes into
      cells. Using this technique, we introduced the cytotoxic drug bleomycin (BLM)
      into cells and examined whether the technique might be useful for the treatment
      of bladder cancer. MATERIALS AND METHODS: For electropermeabilization in vitro,
      we used YTS-1 cells, a human transitional cell carcinoma line. Aliquots of cell
      suspension were mixed with a solution of BLM and immediately exposed to electric
      pulses. A high-power pulse generator was used to supply square-shaped pulses of
      1250 V/cm (100 micros, eight pulses). After a 2-h post-shock incubation, cells
      were washed and incubated for one further hour. Then the concentration of BLM in
      the cells was measured using a bioassay. For electropermeabilization of tissue,
      we used normal male Wistar rats. The bladder was exposed and 10 mg/kg BLM was
      injected into the caudal vein. A series of eight pulses with a time constant of
      100 micros at an electric field intensity of 1000 V/cm was applied. The bladder,
      liver and lungs were extracted 1 h later and prepared for quantification of the
      BLM concentration using the bioassay. RESULTS: Electrotreated cells contained
      significantly higher concentrations of BLM than nonelectrotreated cells. The
      concentration of BLM 1 h after electrotreatment in bladder tissue was 2.7 times
      higher than that in nonelectrotreated bladder tissue. CONCLUSION: The
      electropermeabilization technique has the potential to serve as a new and
      effective modality for the treatment of bladder cancer.

PMID- 8995502
TI  - In vitro effects of R-verapamil on the cytokine environment and T-lymphocyte
      proliferation when human T-lymphocyte activation takes place in the presence of
      acute myelogenous leukemia blasts.
AB  - We investigated the effects of R-verapamil on the cytokine environment and T
      lymphocyte proliferation when human T-lymphocytes were activated in the presence
      of accessory cells containing a large population of acute myelogenous leukemia
      (AML) blasts (nonirradiated blasts for cytokine studies, 50 Gy irradiated blasts
      in proliferation studies). In the presence of AML blasts, R-verapamil inhibited
      interleukin 4 (IL4) and interferon-gamma (IFNgamma) release from polyclonal T
      cell lines activated with the T-cell mitogen phytohemagglutinin (PHA). R
      verapamil also inhibited both the proliferation and the release of IFNgamma and
      IL10 by normal T-cells stimulated with allogeneic peripheral blood mononuclear
      cells derived from AML patients. This antiproliferative effect of R-verapamil was
      seen in the presence of exogenous IL2 but was not observed in the presence of
      exogenous IL1beta or granulocyte/macrophage colony-stimulating factor GM-CSF). In
      addition R-verapamil inhibited the release of IL1beta and tumor necrosis factor
      alpha during allogeneic stimulation.

PMID- 8995503
TI  - Tumor size and origin determine the antitumor activity of cisplatin or 5
      fluorouracil and its modulation by leucovorin in murine colon carcinomas.
AB  - 5-Fluorouracil (FUra) is one of the few effective agents in the treatment of
      patients with colorectal cancer. Its effects on the target enzyme thymidylate
      synthase (TS) can be modulated by leucovorin (LV) or cisplatin (CDDP). Tumor size
      and differentiation of tumor characteristics can influence therapeutic efficacy.
      We therefore studied the relationship between tumor size (cutoff point 200 mm3)
      and the antitumor activity of FUra and its modulation by LV in murine Colon 26
      and Colon 38 tumors. The doubling time of tumors measuring > 200 mm3 was about
      160% longer. The antitumor effect of FUra in these large tumors was decreased and
      could not be modulated by LV. In addition, three subtypes of Colon 26 (Colon 26
      A, Colon 26-B, and Colon 26-10) were identified and characterized for tumor
      induced weight loss, TS activity, response to chemotherapy, and histological
      features. Mice bearing Colon 38 and Colon 26-10 did not lose weight as a result
      of tumor growth. Colon 26-A caused a weight loss of up to 19%, whereas mice with
      Colon 26-B tumors remained within 10% of their initial weight and tolerated at
      least 2.5 times more tumor load than did mice bearing Colon 26-A, which induces
      cachexia. Among untreated tumors, TS catalytic activity was highest in Colon 26-B
      (5536 pmol mg protein(-1) h(-1)) and lowest in Colon 38 (799 pmol mg protein(-1)
      h(-1)); Colon 26-A and Colon 26-10 had intermediate activities (about 2500 pmol
      mg protein(-1) h(-1)). 5-Fluoro-2'-deoxyuridine monophosphate (FdUMP) binding was
      comparable in the three Colon 26 subtypes but was lower in Colon 38. The
      antitumor activity of FUra could be modulated by LV in Colon 38, Colon 26-10, and
      Colon 26-A but could not in Colon 26-B, with complete responses (CR) being
      obtained in Colon 26-10 and Colon 38. The latter two were highly sensitive to
      CDDP, followed by Colon 26-A and Colon 26-B (CRs: 50%, 40%, 25%, and 0,
      respectively). Furthermore, necrosis was noted in Colon 26-B and Colon 38 but not
      in Colon 26-A. In conclusion, (1) the antitumor activity of FUra in large tumors
      is decreased and cannot be modulated by LV and (2) characteristics and
      sensitivity to chemotherapeutics can vary substantially in closely related tumors
      of the same origin.

PMID- 8995504
TI  - Interstitial delivery of carboplatin via biodegradable polymers is effective
      against experimental glioma in the rat.
AB  - PURPOSE: Carboplatin has shown promise experimentally as an antineoplastic agent
      against both primary central nervous system (CNS) tumors and several solid tumors
      that frequently metastasize to the brain. Unfortunately, carboplatin is limited
      in its clinical use for tumors in the CNS by systemic toxicity and poor
      penetration through the blood brain barrier. Recent advances in polymer
      technology have made feasible the intracranial implantation of a biodegradable
      polymer capable of local sustained delivery of chemotherapy for brain neoplasms.
      This study assessed the toxicity and efficacy of carboplatin delivered from
      intracranial sustained release polymers in the treatment of experimental gliomas
      in rodents. METHODS: Two biodegradable anhydride polymer systems were tested: a
      copolymer of 1,3-bis-(p-carboxyphenoxy propane) and sebacic acid, and a copolymer
      of fatty acid dimer and sebacic acid. The polymers were loaded with carboplatin
      and dose escalation studies evaluating toxicity were performed by implanting
      carboplatin-loaded polymers into the brains of rats. Next, efficacy was tested. F
      98 glioma cells were injected intracranially into rats, and 5 days later polymers
      containing the highest tolerated doses were implanted at the site of tumor
      growth. The survival of animals receiving carboplatin-loaded polymer was compared
      with that of animals receiving intraperitoneal doses of the same agent. RESULTS:
      Carboplatin-polymer was well tolerated at doses up to 5% loading in both polymer
      systems. Locally delivered carboplatin effectively prolonged survival of rats
      with F98 gliomas. Maximal treatment effect was seen with 5% loading of either
      polymer, with median survival increased threefold over control (P < 0.004).
      Systemic carboplatin also significantly prolonged survival, but the best
      intracranial polymer dose was significantly more effective than the best systemic
      dose tested. CONCLUSIONS: Carboplatin can be safely delivered intracranially by
      biodegradable sustained- release polymers. This treatment improves survival in
      rodents with experimental gliomas, with locally delivered carboplatin being more
      effective than systemic carboplatin.

PMID- 8995505
TI  - The human cell multiprotein DNA replication complex (MRC): the effect of
      camptothecin on its ability to support in vitro DNA synthesis.
AB  - PURPOSE: We have previously reported on the isolation and characterization of a
      multiprotein DNA replication complex (MRC) from HeLa cells that fully supports in
      vitro DNA replication. Based upon its ability to replicate DNA in a cell-free
      environment (devoid of other cellular processes) the MRC may serve as a unique
      model system for investigating the mechanisms of action of anticancer drugs that
      directly affect DNA synthesis. The experiments described in this report were
      performed to establish whether the MRC could serve as a model system to examine
      in detail the mechanism of action of camptothecin, a DNA topoisomerase I
      inhibitor. METHODS: We examined the effects of increasing concentrations of
      camptothecin on HeLa cell survival, intact HeLa cell DNA synthesis and MRC
      mediated in vitro DNA replication. We also performed topoisomerase I assays in
      the presence of increasing concentrations of camptothecin to study the direct
      effects of the agent on MRC-associated topoisomerase I activity. Furthermore, we
      employed an SDS precipitation assay to measure the formation of MRC-associated
      topoisomerase I-cleavable complexes in the presence of increasing concentrations
      of camptothecin. RESULTS: We found a close correlation between the IC50 values
      for intact HeLa cell DNA synthesis (0.15 microM) and MRC-mediated in vitro DNA
      synthesis (0.05 microM). Similarly, we found that 0.05 microM camptothecin
      inhibited MRC-associated topoisomerase I activity by approximately 50%. In
      addition, we found that the formation of MRC-associated topoisomerase I-cleavable
      complexes increased linearly with increasing concentrations of camptothecin.
      CONCLUSIONS: The data presented in this report support the use of the MRC as a
      model system to study the mechanism of action of camptothecin. We anticipate that
      future studies with the MRC will help elucidate the cellular consequences of
      camptothecin-cleavable complex formation.

PMID- 8995506
TI  - Lyophilized preliposomal formulation of the non-cross-resistant anthracycline
      annamycin: effect of surfactant on liposome formation, stability and size.
AB  - We report a method of preparing a submicron and stable liposome formulation of
      the non-cross-resistant anthracycline annamycin. The lipids were
      dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol
      (DMPG) at a 7:3 molar ratio and the optimal lipid:drug ratio was 50:1 (w/w). The
      selected formulation was a preliposome lyophilized powder that contained the
      phospholipids, annamycin, and Tween 20. The liposome suspension was obtained on
      the day of use by adding normal saline at 37 degrees C (1 ml/mg annamycin) and
      hand shaking for 1 min. The presence of Tween 20 was essential in shortening the
      reconstitution step (from > 2 h to 1 min), avoiding the early formation of free
      drug crystals, and reducing the median particle size by tenfold (from 1.5 microm
      to 0.15 microm) without destroying the liposome vesicles. At room temperature,
      the preliposome powder was chemically stable for > 3 months, and the liposome
      suspension was chemically and physically stable for > 24 h. The in vitro
      cytotoxicity of the formulation was equivalent to that of the same lipid
      composition prepared by the standard evaporation method. The results of the study
      indicate that small amounts of surfactant may be used to enhance the
      reconstitution step and reduce the size of liposome suspensions obtained from
      lyophilized preliposome powders. The formulation described is being used for
      ongoing clinical trials with liposomal annamycin.

PMID- 8995507
TI  - The significance of the sequence of administration of topotecan and etoposide.
AB  - PURPOSE: Often the best method of integrating chemotherapeutic agents is unknown.
      Recently there has been interest in the use of combinations of the topoisomerase
      II inhibitors and the topoisomerase I inhibitors as these agents have shown
      individual activity in malignancies such as non-small-cell lung cancer. This
      study examined the interaction of the topoisomerase II inhibitor etoposide with
      the topoisomerase I inhibitor topotecan (Tpt) in V79 cells (hamster lung
      fibroblast cells) to determine the optimal method of delivering these agents.
      METHODS AND RESULTS: Cell survival was assessed by colony formation. Synergistic
      interactions were assessed by the median effect principle in which a combination
      index (CI) of less than one suggests a synergistic interaction. The V79 cells
      were exposed to sequential 24-h incubations with the two chemotherapeutic agents.
      Initially, equitoxic doses of the two agents were delivered (i.e. 0.0275
      microg/ml of topotecan alone or 0.089 microg/ml of etoposide alone resulting in a
      surviving fraction of 70%; Tpt:etoposide ratio 1: 3.2). It was determined that a
      sequence-dependent synergistic interaction (CI < 1) resulted at a lower level of
      cytotoxicity if the etoposide exposure followed the Tpt exposure compared to the
      opposite sequence. This same effect was seen after treatment of cells with
      various concentration (microg/ml) ratios of Tpt: etoposide (1:4.0, 1:1, 2.5:1).
      CONCLUSIONS: These results suggest that maximum synergy occurs for the delivery
      of etoposide following Tpt exposure (compared to the opposite sequence) and these
      findings may have important clinical implications.

PMID- 8995508
TI  - Effect of angiotensin II on immunotoxin uptake in tumor and normal tissue.
AB  - PURPOSE: To investigate the effect of the sarcosine analog of human angiotensin
      II ([sar]ATII) on the uptake and spatial distribution of immunotoxins (MW 210000
      Da) in RD rhabdomyosarcoma xenografts in mice. This analog has a pressor activity
      similar to native angiotensin II (ATII) but a longer duration of action. METHOD:
      A period of elevated blood pressure of approximately 80 min, measured by
      noninvasive photoplethysmography, was achieved by a 40-min continuous i.p.
      infusion of [sar]ATII at 0.07 microg/min. Tumor-bearing animals were injected
      i.v. with 125I-labeled specific and 131I-labeled nonspecific immunotoxins and
      made hypertensive by i.p. infusion of [sar]ATII. Radioactivity was measured in
      plasma, tumor, liver, kidney and muscle at 2, 6 and 24 h. Plasma radioactivity
      was subtracted from tissue values to calculate tissue uptake. To assess the
      spatial distribution of immunotoxin in the solid tumor, 125I-labeled specific
      immunotoxin was injected i.v. into tumor-bearing animals, and quantitative
      autoradiography was performed on tumor sections. RESULTS: The uptake of specific
      or nonspecific immunotoxins in tumor and normal tissues was not significantly
      different in [sar]ATII-hypertensive animals compared with saline-treated
      controls. In control animals. the spatial distribution of 125I-labeled specific
      immunotoxins was very heterogeneous and contained punctate accumulations
      throughout the tumor. Treatment with [sar]ATII did not affect this distribution
      qualitatively or quantitatively. To examine a possible reason for the lack of
      [sar]ATII effect, we measured the interstitial pressure of the RD tumor using a
      fluid-filled micropipette connected to a servo-null pressure transducer. The
      interstitial pressure in this solid tumor was unexpectedly low, only 0.6 +/- 0.9
      mm Hg. CONCLUSIONS: The sustained period of [sar]ATII-induced hypertension had no
      effect on RD tumor or normal tissue uptake or tumor spatial distribution of
      immunotoxin. In saline-treated controls, the heterogeneity of immunotoxin
      distribution does not arise from an elevated interstitial pressure. Further
      studies are needed to determine whether a correlation exists between
      responsiveness to ATII-induced hypertensive chemotherapy using macromolecular
      drugs and tumor type and/or physiological properties.

PMID- 8995509
TI  - Influence of route of administration on [3H]-camptothecin distribution and tumor
      uptake in CASE-bearing nude mice: whole-body autoradiographic studies.
AB  - Camptothecin (CPT) inhibits the growth of a wide variety of experimental tumors.
      As a part of our exploration of this drug for use as a cancer chemotherapeutic
      agent, we studied the effect of route of administration on the absorption,
      distribution and tumor uptake of [3H]-CPT. The rate of disappearance of [3H]-CPT
      derived radioactivity from blood during the first 48 h was highest following oral
      than following intravenous (i.v.) administration. Thereafter blood levels were
      low irrespective of route of administration. Considerable [3H]-CPT-derived
      radioactivity was detected in urine and feces up to 48 h after dosing.
      Distribution studies were conducted using quantitative whole-body autoradiography
      (WBA). These studies revealed that independent of the route of administration,
      [3H]-CPT was rapidly excreted in the bile (gallbladder) followed by elimination
      into the small and large intestinal tract. Levels of CPT-derived radioactivity in
      the kidneys were minimal and mostly localized in the renal pelvis. Hepatic
      concentrations of CPT were low and were almost equal to those of the tumor. The
      lungs of animals treated i.v. showed higher uptake of radioactivity than those
      treated intramuscularly or orally. Tumor/blood ratios were slightly higher
      following oral administration than following administration by other routes. This
      study indicates that CPT is primarily eliminated via the bile. The
      gastrointestinal tract is the major site of accumulation and excretion of CPT.

PMID- 8995510
TI  - Relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity
      after intravenous infusions of cisplatin to cancer patients.
AB  - PURPOSE: The relationships between pharmacokinetic parameters of unchanged
      cisplatin (CDDP) and several markers for nephrotoxicity after CDDP infusion (80
      mg/m2) over 2 and 4 h were quantitated in patients with various cancers (lung,
      stomach and colon cancers and mediastinal tumor). METHODS: Plasma and urinary
      levels of unchanged CDDP were measured using a specific high-performance liquid
      chromatography method. Pharmacokinetic parameters were calculated according to
      the model-independent method. The nephrotoxicity markers, blood urea nitrogen
      (BUN), serum creatinine (SCr), plasma and urinary beta2-microglobulin (BMGp and
      BMGu), urinary N-acetyl-beta-D-glucosaminidase (NAG) and creatinine clearance
      (CCR) were monitored for 30 days following CDDP administration. RESULTS: The
      maximum plasma concentration (Cmax), maximum urinary excretion rate
      (dAe/dt(max)), area under the plasma concentration-time curve from time zero to
      infinity (AUC), cumulative amount excreted in urine from time zero to infinity
      (Ae), total clearance (Clt), renal clearance (Clr) and plasma half-life (t1/2) of
      unchanged CDDP were not significantly different between the 2-h and 4-h infusion
      schedules. The values of the nephrotoxicity markers changed significantly
      following CDDP administration, suggesting that CDDP chemotherapy (80 mg/m2)
      caused nephrotoxicity. The Cmax of unchanged CDDP was the most informative
      pharmacokinetic parameter for nephrotoxicity. Cmax was related to maximum BUN,
      maximum SCr and minimum CCR levels in 27 CDDP treatments according to an
      exponential model. CONCLUSION: In order to attain more effective CDDP
      chemotherapy with minimum nephrotoxicity, the present pharmacokinetic and
      pharmacodynamic studies suggest that the Cmax or steady-state plasma level of
      unchanged CDDP should be maintained between 1.5 and 2 microg/ml in a standard
      continuous infusion schedule over 2 h and 4 h.

PMID- 8995511
TI  - The effect of vincristine-polyanion complexes in STEALTH liposomes on
      pharmacokinetics, toxicity and anti tumor activity.
AB  - Poly(ethylene glycol) (PEG)-derivatized liposome vehicles improve antitumor
      effectiveness of entrapped anthracyclines and vinca alkaloids. However, the
      plasma clearance of entrapped vincristine is substantially faster than the lipid
      phase or other entrapped aqueous markers, suggesting leakage out of the liposome
      during transit in the blood compartment. We tested the effect of altering the
      drug's in vivo leakage rate on pharmacokinetics, toxicity, and antitumor activity
      of entrapped drug in rodent models. Suramin, heparin, and dextran sulfate were
      tested for their ability to produce a precipitable complex in vitro. PEG
      derivatized liposomes were prepared with the complexing agent inside, and
      vincristine was driven inside using an ammonium gradient. The resulting
      preparations were found to have plasma distribution half-lives significantly
      longer than the formulation without a complex-forming agent. There was no
      increase in acute lethality, and in the case of the suramin-vincristine complex,
      the acute lethality was significantly reduced at the highest does level. Anti
      tumor activity against the mouse mammary carcinoma MC2 was tested in a multiple
      dose study. Free vincristine did not affect the tumor growth rate significantly,
      but at the same dose level all PEG-coated liposome formulations inhibited tumor
      growth markedly. The suramin containing formulation was as effective as the
      formulation lacking polyanion, but the heparin and dextran sulfate containing
      formulations were less effective. Thus, compounds which form insoluble complexes
      with vincristine alter in vivo plasma distribution phase pharmacokinetics without
      increasing acute lethality, but without a corresponding increase in anti-tumor
      activity.

PMID- 8995513
TI  - Vinorelbine-induced neurotoxicity in patients with advanced breast cancer
      pretreated with paclitaxel--a phase II study.
AB  - Vinorelbine (VNB) shows high antitumoral activity in advanced breast cancer due
      to its high affinity for mitotic tubulin and differs from the other vinca
      alkaloids with regard to its low degree of neurotoxicity because of its low
      affinity for axonal tubulin. Preclinical data show the existence of different
      binding sites on tubulin for vinca alkaloids and paclitaxel (P), suggesting a
      lack of cross-resistance. Thus, VNB was chosen eligible for a phase II study to
      evaluate both the therapeutic efficacy and the toxicity of VNB in patients (pts)
      with advanced breast cancer failing first- or second-line chemotherapy with P. A
      total of 14 pts with advanced breast cancer pretreated with P were entered into
      the study. Therapy consisted of VNB at 30 mg/m2 diluted in 500 ml of normal
      saline given over 30 min after a minimal interval of 4 weeks since the last
      application of P. For the first four cycles, injections were repeated at 2-week
      intervals; thereafter they were repeated at 3-week intervals until evidence of
      progressive disease or severe toxicity developed. All but one pt was considered
      assessable for response and all pts were evaluable for toxicity. No objective
      response was observed; two pts showed no change in their disease. In four pts
      therapy had to be stopped because peripheral neurotoxicity increased from a
      pretherapeutic level after therapy with P from National Cancer Institute Common
      Toxicity Criteria (NCI-CTC) grade 1 (n = 3) and 2 (n = 1) to neurotoxicity grade
      3 after 1, 2 (n = 2), and 3 cycles of therapy with VNB, respectively. In
      addition, constipation of grade 2 occurred in 10 pts. Hematologic toxicity was
      negligible. No other evaluable toxicity exceeded NCI-CTC grade 1. Both
      observations of this study, the complete resistance to VNB and the increase in
      peripheral neuropathy, let us assume the existence of a preclinically not
      anticipated but clinically relevant cross-resistance between these two spindle
      poisons and the presence of common functional targets. Therefore, P-pretreated
      pts should be excluded from consecutive VNB-containing therapies.

PMID- 8995512
TI  - Myelotoxic effects of the bifunctional alkylating agent bizelesin on human,
      canine and murine myeloid progenitor cells.
AB  - Bizelesin is a potent synthetic derivative of the anticancer agent CC-1065 that
      preferentially alkylates and binds the minor grove of DNA. Preclinical animal
      studies have found bizelesin to be more toxic to beagle dogs than to rodents and
      that myelosuppression was the dose-limiting toxicity. This toxicity was dose- and
      time-dependent in all species. Due to the significant difference in the in vivo
      myelotoxicity between species, it was important to determine which one most
      closely resembles humans on a pharmacodynamic basis. Therefore, hematopoietic
      clonal assays were utilized to evaluate the effects of bizelesin on granulocyte
      macrophage (CFU-gm) colony formation. Marrow cells were exposed in vitro to
      bizelesin (0.001-1000 nM) for 1 or 8 h and then assayed for colony formation.
      There was a 3-log difference in drug concentration at which 100% colony
      inhibition occurred (1 or 8 h) for murine CFU-gm versus human or canine CFU-gm.
      The IC70 value after an 8-h bizelesin exposure for human CFU-gm (0.006 +/- 0.002
      nM) was 2220-times lower than for murine CFU-gm (13.32 +/- 8.31 nM). At any given
      concentration, an 8 h drug exposure resulted in greater colony inhibition than a
      1 h exposure for all species (P < 0.05). Increasing exposure time from 1 to 8 h
      increased toxicity to human and canine CFU-gm much more than to murine CFU-gm.
      The clinically formulated drug solution was a more potent inhibitor of human
      colony formation than drug dissolved in DMSO. The IC70 value after a 1-h exposure
      was 1.7 times lower for human CFU-gm with formulated bizelesin (0.106 +/- 0.105
      nM) than bulk drug in DMSO (0.184 +/- 0.044 nM). The results of these in vitro
      clonal assays were qualitatively consistent with those seen in whole animal
      studies, suggesting that bizelesin will be a potent myelosuppressive agent in the
      clinic. Since the dose-limiting toxicity in preclinical models is
      myelosuppression and the in vitro sensitivity of human and canine CFU-gm is
      similar, the canine maximum tolerated dose (MTD) is better than the murine MTD to
      determine a safe starting dose for phase I clinical trials.

PMID- 8995514
TI  - Comparative activity of idarubicin and idarubicinol in combination with
      cyclosporin A in multidrug-resistant leukemia cells.
AB  - 4-Demethoxydaunorubicin (idarubicin, IDA) is an anthracycline that has shown good
      cytotoxic activity in vitro against tumor cell lines displaying the multidrug
      resistant (MDR) phenotype. IDA is converted in the liver into idarubicinol
      (2HIDA) and, in this form, seems to exert its antitumoral activity in vivo.
      Recent studies have shown that 2HIDA has tumoricidal activity similar to that of
      the parent drug when tested in vitro in sensitive neoplastic cells. In this work
      we compared in vitro the effects of IDA and 2HIDA used alone and in combination
      with 2 microM cyclosporin A (CyA) in the MDR leukemic cell lines FLCR and K562R
      and in their sensitive parent cell lines FLC and K562. IDA and 2HIDA showed the
      same cytotoxic activity in sensitive cells. After 1 h of exposure of cells to
      each anthracycline, we observed that the cellular uptake of IDA and 2HIDA was
      also similar. In resistant cells, 2HIDA was 3-4 times less active than IDA. We
      observed that the intracellular uptake of 2HIDA was lower than that of IDA, and
      this may be correlated with a greater ability of P-glycoprotein to expel 2HIDA as
      opposed to IDA. Indeed, when MDR cells were exposed to IDA and 2HIDA in
      combination with 2 microM CyA, the cytotoxic effect of these anthracyclines was
      the same, and it was similar to that observed in sensitive cells. These data
      confirm the utility of the combination of IDA and an MDR-reversing agent in
      hematological malignancies displaying the MDR phenotype.

PMID- 8995515
TI  - Pharmacokinetics of amifostine and its metabolites in the plasma and ascites of a
      cancer patient.
AB  - The pharmacokinetics of amifostine, a protector against chemotherapy and
      radiation-induced toxicities, was investigated in the plasma and ascites of a
      cancer patient. A high-performance liquid chromatography (HPLC) procedure with
      electrochemical detection was used to measure amifostine, its active metabolite,
      WR 1065, and the disulfides (symmetrical plus mixed disulfides). Both amifostine
      and WR 1065 were rapidly cleared from the plasma (95% and 50% of the peak
      concentration within 1 h, respectively). The disulfides, which were rapidly
      formed from WR 1065, were cleared much more slowly (final half-life 13.6 h).
      Multiple dosing resulted in a tendency toward increasing peak levels of WR 1065
      and decreasing peak levels of the disulfides. Only 1% of the delivered dose
      appeared in the ascites. Therefore, it is not plausible that the presence of
      ascites or other third spaces would have an impact on the pharmacokinetics of
      amifostine.

PMID- 8995516
TI  - Photodynamic damage to HeLa cell microtubules induced by thiazine dyes.
AB  - The aim of this study was to analyze possible alterations of the microtubule
      cytoskeleton of cultured cells subjected to photodynamic treatments with the
      thiazine dyes methylene blue or toluidine blue. Indirect immunofluorescence
      labeling of alpha-tubulin was performed in HeLa cells after 1 or 18 h of
      incubation with thiazines followed by red-light irradiation for 15 min [leading
      to surviving fractions (SF) of about 65% (SF65) or 1% (SF1), respectively].
      Untreated control cells showed the normal distribution of interphase
      microtubules, whereas considerable or severe disorganization of the microtubule
      network was observed after SF65 or SF1 photodynamic treatments, respectively. A
      great amount of blebs showing homogeneous fluorescence was also found on the cell
      surface after SF1 treatments. Possible mechanisms responsible for the photodamage
      to microtubules induced by thiazine dyes are briefly discussed.

PMID- 8995517
TI  - The tissue distribution in BALB/c mice of C-14-labeled JM216, an orally active
      platinum antitumour compound.
AB  - The ammine/amine platinum(IV) dicarboxylates have been developed as orally active
      platinum antitumor agents, and one of these, [PtCl2(NH3)(C6H11NH2) (OCOCH3)2]
      (JM216), is undergoing clinical trials at present. A synthesis method was
      developed to radiolabel JM216 with carbon 14 at the carboxylate carbon. The
      labeling efficiency was 92%, and the purity as shown by high-performance liquid
      chromathography (HPLC) was 96% after recrystallisation. The radiolabeled JM216
      was given orally to BALB/c mice and detailed tissue-distribution data were
      obtained (blood plasma, kidney, liver, spleen, brain, lung, muscle and skin) for
      time points of 2 h and 2, 6 and 10 days. Comparison of these data with previously
      reported data for distribution of platinum obtained by atomic absorption
      spectroscopy has shown distinct differences, especially for the liver and the
      kidney. This clearly indicates a difference in behaviour between the labeled
      ligand and the platinum centre, suggesting detachment of the ligand in vivo.

PMID- 8995518
TI  - Vinca alkaloids and macrolides in human immunodeficiency virus-related
      malignancies: a safe association.

PMID- 8995519
TI  - Escherichia coli lac repressor-lac operator interaction and the influence of
      allosteric effectors.
AB  - The wild type E. coli lac operator is embedded in a 35 base-pair DNA sequence
      containing extensive 2-fold symmetry, suggesting a symmetric repressor operator
      complex. However, deviations from strict 2-fold symmetry occur at the central
      base-pair and at three additional base-pairs. Using an operator fragment binding
      analysis we have determined: (a) a relative contribution each pair provides to
      the lac repressor-lac operator DNA complex, (b) the operator DNA length necessary
      for maximum binding to lac repressor; and (c) the contribution of the several non
      symmetric base in the wild-type operator to the binding affinity. Since lac
      repressor-lac operator DNA interaction is reduced upon binding of the gratuitous
      inducer, isopropyl-beta-D-galactoside (IPTG), the same DNA fragment binding
      analysis was performed with the low affinity form of lac repressor. In the
      presence of inducer, the affinity for the left half site of the wild-type lac
      operator is reduced without significant reduction on the right half of the
      operator. Conversely, the anti-inducer orthonitrophenylfucoside (ONPF) which
      stabilizes the lac repressor-lac operator complex increases the binding affinity,
      particularly to the right half of the operator.

PMID- 8995520
TI  - A model for the mechanism of polymerase translocation.
AB  - A general mechanism for polymerase translocation is elaborated. The central
      feature of this mechanism is that a rapid translocational equilibrium is
      established after each cycle of nucleoside monophosphate incorporation such that
      the polymerase distributes itself by diffusional sliding between all accessible
      positions on the template with relative occupancy determined by relative free
      energy. While alternative models for translocation have not been fully developed,
      much of the language currently used to describe this step suggests an active
      mechanism coupled to conformational transitions in the polymerase. For example, a
      recent study of force generation by Escherichia coli RNA polymerase during
      transcription suggests that it is a mechanoenzyme analogous to kinesin of myosin
      motor proteins. While the proposed mechanism does not rule out conformational
      transitions during polymerase translocation, it suggests that they may be
      unnecessary and that translocation can be explained in terms of the affinity of
      the active site for nucleoside triphosphate and the relative free energies of the
      polymerase bound at different positions on the template. This mechanism makes
      specific predictions which are borne out experimentally with polymerases as
      distinct as E. coli DNAP I, phage T7 RNAP, and E. coli RNAP.

PMID- 8995522
TI  - Binding and cleavage of nicked substrates by site-specific recombinases XerC and
      XerD.
AB  - In Xer site-specific recombination two related recombinases, XerC and XerD,
      catalyse strand cleavage and rejoining reactions at a site, dif, in order to
      ensure normal chromosome segregation during cell division in Escherichia coli. We
      have used nicked suicide substrates to trap reaction intermediates and show that
      XerC cleaves the top strand efficiently while XerD is less efficient at cleaving
      the bottom strand of dif. Recombinase-mediated cleavage positions are separated
      by six base pairs and occur at either end of the dif central region adjacent to
      the recombinase binding sites. XerC can cleave the top strand of dif
      inefficiently in the absence of its partner recombinase during a reaction that
      does not require intermolecular synapsis. The presence of a nick in the bottom
      strand of dif allows cooperative interactions between two XerC protomers bound to
      adjacent binding sites, suggesting that a conserved interaction domain is present
      in both XerC and XerD. Cooperativity between two identical recombinase protomers
      does not occur on un-nicked linear DNA. Ethylation interference footprinting of
      two XerD catalytic mutant proteins suggests that the conserved domain II arginine
      from the integrase family RHRY tetrad may make direct contact with the scissile
      phosphate.

PMID- 8995521
TI  - The bifunctional protein DCoH modulates interactions of the homeodomain
      transcription factor HNF1 with nucleic acids.
AB  - The hepatocyte nuclear factor-1 (HNF1) is a homeodomain transcription factor that
      binds DNA as a dimer. HNF1 dimers associate with two molecules of DCoH, a
      bifunctional protein that also has an enzymatic function in the
      tetrahydrobiopterin regeneration, to form stable heterotetramers also capable of
      DNA binding. Employing purified, recombinant HNF1, HNF1/DCoH heterotetramers and
      DCoH homotetramers we investigated whether DCoH affects interactions of HNF1 with
      nucleic acids. Although we detected no direct binding of DCoH to DNA or RNA, DCoH
      stabilized HNF1/DNA complexes and promoted interactions with sub-optimal DNA
      target sequences such as the human alpha1-antitrypsin TATA box region.
      Importantly, we also observed interactions of HNF1 with RNA, but these
      interactions were completely abolished when HNF1 was complexed with DCoH.
      Interestingly, DCoH retains its enzymatic activity while complexed with HNF1. Our
      results document intermolecular regulation of HNF1 binding to nucleic acids by
      DCoH.

PMID- 8995523
TI  - Myosin rod protein: a novel thick filament component of Drosophila muscle.
AB  - Myosin rod protein (MRP), a 155 kDa protein encoded by a gene internal to the
      Drosophila muscle myosin heavy chain (Mhc) gene, contains the MHC rod domain, but
      has 77 unique N-terminal residues that exactly replace the MHC motor and light
      chain binding domains. Originally described as an abundant testis protein, we now
      demonstrate the MRP also is a major component of myofilaments in Drosophila.
      Specifically, the Mrp promoter directs the expression of a LacZ reporter
      transgene in somatic, cardiac and visceral muscles. MRP-specific antibodies
      detect the protein in detergent-insoluble fractions of muscle extracts and co
      localize the protein with MHC to the sarcomeric A-band in immunostained muscles.
      Immunoblot analysis shows that in a set of adult direct flight muscles (DFM), the
      ratio of MRP to MHC is 1:3. Chemical cross-link and co-immunoprecipitation
      experiments using 0.5 M KCl-extracted thick filament proteins indicate that
      native MRP is a homodimer. Electron microscopy of DFM49, which has a high MRP
      content, shows in cross section, disordered myofilament packing and a variable
      thin to thick filament ratio and, in longitudinal section, severely bent thin
      filaments that are not well associated with thick filaments. In rigor, thick
      filaments from DFM49 consist of segments with cross bridges that are interspersed
      with smooth domains lacking cross bridges. These data indicate that MRP is a
      novel contractile protein that co-integrates with myosin into the thick filament,
      thereby changing structure and function of the sarcomere.

PMID- 8995524
TI  - Differential binding of S-adenosylmethionine S-adenosylhomocysteine and
      Sinefungin to the adenine-specific DNA methyltransferase M.TaqI.
AB  - The crystal structures of the binary complexes of the DNA methyltransferase
      M.TaqI with the inhibitor Sinefungin and the reaction product S-adenosyl-L
      homocysteine were determined, both at 2.6 A resolution. Structural comparison of
      these binary complexes with the complex formed by M.TaqI and the cofactor S
      adenosyl-L-methionine suggests that the key element for molecular recognition of
      these ligands is the binding of their adenosine part in a pocket, and
      discrimination between cofactor, reaction product and inhibitor is mediated by
      different conformations of these molecules; the methionine part of S-adenosyl-L
      methionine is located in the binding cleft, whereas the amino acid moieties of
      Sinefungin and S-adenosyl-L-homocysteine are in a different orientation and
      interact with the active site amino acid residues 105NPPY108. Dissociation
      constants for the complexes of M.TaqI with the three ligands were determined
      spectrofluorometrically. Sinefungin binds more strongly than S-adenosyl-L
      homocysteine or S-adenosyl-L-methionine, with KD=0.34 microM, 2.4 microM and 2.0
      microM, respectively.

PMID- 8995525
TI  - Protein binding versus protein folding: the role of hydrophilic bridges in
      protein associations.
AB  - The role of hydrophilic bridges between charged, or polar, atoms in protein
      associations has been examined from two perspectives. First, statistical analysis
      has been carried out on 21 data sets to determine the relationship between the
      binding free energy and the structure of the protein complexes. We find that the
      number of hydrophilic bridges across the binding interface shows a strong
      positive correlation with the free energy; second, the electrostatic contribution
      of salt bridges to binding has been assessed by a continuum electrostatics
      calculation. In contrast to protein folding, we find that salt bridges across the
      binding interface can significantly stabilize complexes in some cases. The
      different contributions of hydrophilic bridges to folding and to binding arise
      from the different environments to which the involved hydrophilic groups are
      exposed before and after the bridges are formed. These groups are more solvated
      in a denatured protein before folding than on the surface of the combining
      proteins before binding. After binding, they are buried in an environment whose
      residual composition can be much more hydrophilic than the one after folding. As
      a result, the desolvation cost of a hydrophilic pair is lower, and the favorable
      interactions between the hydrophilic pair and its surrounding residues are
      generally stronger in binding than in folding. These results complement our
      recent finding that while hydrophobic effect in protein-protein interfaces is
      significant, it is not as strong as that observed in the interior of monomers.
      Taken together, these studies suggest that while the types of forces in protein
      protein interaction and in protein folding are similar, their relative
      contributions differ. Hence, association of protein monomers which do not undergo
      significant conformational change upon binding differs from protein folding,
      implying that conclusions (e.g. statistics, energetics) drawn from investigating
      folding may not apply directly to binding, and vice versa.

PMID- 8995526
TI  - p53 Phosphorylation: biochemical and functional consequences.
AB  - The p53 protein plays a vital role in suppressing the development of cancer.
      Posttranslational modification through phosphorylation has been postulated to be
      an important regulatory mechanism of p53 function. Data describing the role of
      phosphorylation in terms of its effects on several biochemical properties and
      cellular functions of p53 are examined in the context of how p53 might be
      "phospho-regulated."

PMID- 8995527
TI  - Oxidative-stress associated parameters (lactoferrin, superoxide dismutases) in
      serum of patients with Alzheimer's disease.
AB  - In this case/control study, serum levels of oxidative stress related parameters
      such as Fe-binding lactoferrin (LTF), Mn- and Zn,Cu-superoxide dismutase (SOD)
      were determined by enzyme linked immunoassays in patients suffering from the
      Alzheimer's dementia as well as in non-demented controls. The Mn-SOD
      concentration was significantly (P<0.05, U-test) reduced in patients suffering
      from Alzheimer's disease if compared to non-demented controls. The other
      parameters investigated did not differ significantly between both groups. Our
      findings give evidence for the hypothesis of a disturbed free radical metabolism
      in Alzheimer's disease. The specificity of these results remains to be clarified.
      Further studies are needed to elucidate the relevance of oxidative stress in the
      etiopathogenesis of the Alzheimer's disease.

PMID- 8995528
TI  - Dolichol and vitamin A content in rat liver Ito (perisinusoidal) cells.
AB  - Dolichol has been determined in many tissues but to date no data are available on
      liver Ito (fat storing) cells. In this note dolichol was determined in two
      subpopulations of liver Ito cells isolated from rats pretreated with vitamin A:
      Ito-1, vitamin A enriched and Ito-2, relatively poor of vitamin A. Differences
      were observed in the behaviour of the two fractions after vitamin A pretreatment
      of rats. In fact, in Ito-1 fraction dolichol increases with the increase of
      vitamin A, while in Ito-2 fraction it does not change significantly with the
      increase of vitamin A. These results, while confirming the heterogeneity of fat
      storing cells, are discussed as to the possible role of dolichol and vitamin A
      metabolism.

PMID- 8995529
TI  - Effects of structural modulation on biological activity of bombesin analogues
      with (E)-alkene bond.
AB  - The specific bombesin receptor antagonist, (E)-alkene bombesin isostere (EABI-1),
      [D-Phe6,Leu13psi[(E)CH=CH]Leu14]bombesin(6-14) is a potent antagonist in terms of
      inhibition of bombesin-stimulated amylase release from rat pancreatic acini. This
      study examined the effects of EABI-1 (L-L diastereomer) and three novel bombesin
      analogues on amylase release in rat pancreatic acini. EABI-2 is a L-D
      diastereomer of EABI-1. EABI-3 is an analogue, of which leucine at position 13 of
      EABI-1 was replaced with valine. EABI-4 is a L-D diastereomer of EABI-3 (L-L).
      The order of agonist potency was EABI-2>EABI-3>EABI-4. EABI-1 showed no agonist
      activity at concentrations up to 100nM. On the other hand, all of four analogues
      had antagonist activity. The order of antagonist potency was EABI-1>EABI-3>EABI
      4>EABI-2. EABI-1 was a complete antagonist, EABI-2 and EABI-3 were partial
      agonists, and EABI-4 had a weak agonist effect. The present study provides a
      useful information on the future development of peptide analogues for anticancer
      agents and biological tools for investigating actions of bombesin family
      peptides.

PMID- 8995530
TI  - Vitamin D receptor gene expression in human pituitary gland.
AB  - 1,25-dihydroxyvitamin D3 has important physiological effects such as calcium
      transport and cell growth and differentiation. These biological effects are
      mediated by their binding to specific intracellular receptor termed vitamin D
      receptor (VDR). VDR mRNA expression has been demonstrated in several tissues, but
      to date, there is no information about its presence in the human pituitary gland.
      In this report, we demonstrate VDR mRNA expression using the reverse
      transcription-polymerase chain reaction (RT-PCR), as well as the cellular
      expression of VDR by immunohistochemistry, both in the human pituitary gland.
      These results suggest the possibility that, like in the rat pituitary, VDR may
      regulate the human pituitary gene expression and hormone secretion.

PMID- 8995531
TI  - Effect of r-interferon alpha administration on hypothalamus-pituitary-thyroid
      axis in chronic hepatitis.
AB  - Recent studies pointed out the development of autoimmune thyroid diseases during
      interferon (IFN) therapy, mainly in patients with positive thyroid autoantibodies
      (MsAb and TgAb) before treatment. The effects of recombinant human IFN alpha
      (rhIFNalpha) on thyroid function and thyroid autoantibodies were studied in 12
      patients with chronic active hepatitis associated with virus B or C, selected on
      the basis of negative results for MsAb and TgAb. No significant variation in T3,
      T4 and TSH levels was observed either after the first administration of rhIFN
      alpha (3 million IU i.m.) or after three months of therapy (3 million IU i.m. 3
      times a week). TSH response to TRH was in the normal range either before or after
      the therapy. The absence of MsAb and TgAb was confirmed in all the patients at
      the end of the treatment. These results indicate that no patient developed
      thyroid disorder during IFN therapy. Nevertheless, since positive MsAb and TgAb
      have been considered as a risk factor for thyroid diseases, in patients selected
      for IFN therapy they should be carefully assessed for autoantibodies before
      undergoing IFN treatment.

PMID- 8995532
TI  - Activities of liver pyruvate dehydrogenase complex and 3-hydroxyacyl-CoA
      dehydrogenase in sand rat (Psammomys obesus).
AB  - The sand rat (Psammomys obesus) is an animal model for non-insulin dependent
      diabetes mellitus, which is induced by a regular chow diet. The total activity of
      liver pyruvate dehydrogenase complex in the sand rats under normoglycemic and
      normoinsulinemic conditions was one half as high as that in the albino rats, but
      the activity of liver 3-hydroxyacyl-CoA dehydrogenase was more than 4 times
      greater in the former than in the latter, suggesting a low capacity for glucose
      oxidation and a high capacity for fatty acid oxidation in the sand rats. These
      metabolic conditions may be related to the predisposition of the animals towards
      diabetes. Diet-induced diabetes in the sand rats resulted in decreasing the
      active form of liver pyruvate dehydrogenase complex and in increasing the
      activity of liver 3-hydroxyacyl-CoA dehydrogenase, suggesting that the diabetic
      conditions further suppress glucose oxidation and promote fatty acid oxidation.

PMID- 8995533
TI  - Dimeric tubulin-stimulated adenylyl cyclase activity is augmented after long-term
      amitriptyline treatment.
AB  - We have investigated altered association of tubulin dimers interacting with G
      proteins and modulating adenylyl cyclase (AC) as a result of long-term
      amitriptyline (AMT) treatment. Gpp(NH)p-stimulated, but not basal or manganese
      stimulated, AC activity was significantly augmented in cortex membranes prepared
      from rats chronically treated with AMT. The enhancement of AC activity by
      Gpp(NH)p-liganded tubulin (tubulin-Gpp(NH)p) was significantly higher in
      chronically AMT-treated rats than in control rats. Moreover, in cortex membranes
      from controls, tubulin-Gpp(NH)p prepared from chronically AMT-treated rats was
      more effective to activate AC activity than tubulin-Gpp(NH)p from controls.
      Immunoblotting and photoaffinity guanine nucleotide binding procedures showed no
      significant differences in the amount and the function of G proteins between
      controls and AMT-treated groups. It is suggested that long-term AMT treatment
      causes alteration in the functional interaction between tubulin and G protein,
      and this modification may participate in enhanced coupling of Gs to the catalytic
      subunit of AC induced by the chronic antidepressant treatment.

PMID- 8995535
TI  - Context-dependent cross-sensitization between cocaine and amphetamine.
AB  - We investigated the effect of amphetamine pretreatment on the locomotor response
      to subsequent cocaine challenge. Rats were administered either 0.75 mg/kg
      amphetamine in a testing environment and saline in their home cage, saline in the
      testing environment and 0.75 mg/kg amphetamine in their home cage, or saline in
      both the testing environment and home cage. After 5 pairings of drug to
      environment, conditioning was tested by administration of a saline injection.
      Both amphetamine treated groups exhibited increased locomotion in response to
      saline injection. After the eighth session of the pairing regimen, all animals
      were administered 5 mg/kg cocaine in the test environment and their behavior
      measured for 30 min. Sensitization to cocaine was observed only in rats with
      previous amphetamine exposure in the testing environment. There was no difference
      between groups in whole brain, striatal, or plasma levels of cocaine. The data
      support the hypothesis that sensitization is independent of brain cocaine levels.

PMID- 8995534
TI  - Cytokine induction of cytosolic phospholipase A2 and cyclooxygenase-2 mRNA is
      suppressed by glucocorticoids in human epithelial cells.
AB  - Prostaglandin (PG) release, which is increased in vivo by inflammatory conditions
      and in vitro by pro-inflammatory cytokines, is decreased by glucocorticoids. Two
      phospholipase A2 isoforms, secretory (sPLA2) and cytosolic (cPLA2,), have been
      implicated in inflammation. These enzymes catalyse the release of arachidonic
      acid which is then converted to prostaglandins by the cyclooxygenases (COX-1 and
      COX-2). Regulation of these events at the mRNA level is poorly characterised in
      epithelial cells. We have used a human epithelial-like cell line (A549) as a
      model system to study mRNA expression of sPLA2, cPLA2, COX-1 and COX-2. Following
      treatment of cells and extraction of RNA, semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) was used to examine expression of these genes.
      We show a coordinate induction of both cPLA2 and COX-2 mRNA by pro-inflammatory
      cytokines which correlated with increased PGE2 release. By contrast, sPLA2 mRNA
      was undetectable and COX-1 was found to be expressed at a constant low level. In
      addition dexamethasone pretreatment significantly reduced both cPLA2 and COX-2
      mRNA levels as well as PGE2 release following cytokine stimulation. These data
      indicate a major role for control of prostaglandin synthesis at the mRNA level of
      key synthetic genes in epithelial cells. Furthermore we show that a major
      mechanism of glucocorticoid action in preventing prostaglandin release occurs by
      suppression of cPLA2 and COX-2 mRNA levels.

PMID- 8995536
TI  - Oral ketamine produces a dose-dependent CNS depression in the rat.
AB  - The oral to parenteral potency of ketamine to produce central nervous system
      (CNS) depression was estimated in rats using a behavioral scale. As a function of
      dose, ketamine produces CNS depression that ranges from ataxia to anesthesia by
      either route of administration. The oral ED50 value for ketamine was 120 mg/kg
      (82.2-159.2, 95% CI) while the intravenous ED50 value was 3.7 mg/kg (2.4-5.1, 95%
      CI). Oral ketamine produces CNS effects comparable to intravenous ketamine,
      although the drug is approximately 32 fold less potent by the oral route.

PMID- 8995538
TI  - Cytoreductive surgery for the management of stage IV ovarian cancer.

PMID- 8995537
TI  - Diuretic and antinatriuretic responses produced by the endogenous opioid-like
      peptide, nociceptin (orphanin FQ).
AB  - Nociceptin (orphanin FQ) is a novel peptide isolated from brain tissue that has
      an amino acid sequence most similar to that of the endogenous opioid peptide
      dynorphin A. Aside from this similarity, the association of nociceptin to the
      endogenous opioid peptide systems and the functional importance of this new
      peptide in vivo are not completely known. Here we report that nociceptin is
      physiologically active in vivo and produces marked changes in the renal excretion
      of water and sodium. In conscious Sprague-Dawley rats, intravenous infusion of
      nociceptin produced a profound increase in urine flow rate and decrease in
      urinary sodium excretion. In further studies, intracerebroventricular (i.c.v.)
      injection of nociceptin into conscious rats produced a concurrent diuresis (dose
      dependent) and antinatriuresis. The magnitude and pattern of the central
      nociceptin-induced water diuresis was similar to that produced by i.c.v.
      dynorphin A. Whereas i.c.v. pretreatment with the selective kappa-opioid receptor
      antagonist, nor-binaltorphimine, completely prevented the renal responses
      produced by dynorphin A, this antagonist did not alter the diuresis or
      antinatriuresis produced by central nociceptin. Thus, these results indicate that
      in conscious rats, nociceptin produces a selective water diuresis via a central
      nervous system mechanism independent of kappa-opioid receptors. Together, these
      observations suggest that endogenous nociceptin may be a novel peptide involved
      in the central control of water balance and ultimately in the regulation of
      arterial blood pressure. In the future, analogues of nociceptin may prove to be
      the first clinically useful water diuretics for patients with water-retaining
      diseases.

PMID- 8995539
TI  - Effect of surgical debulking on survival in stage IV ovarian cancer.
AB  - In order to determine whether optimal surgical debulking in Stage IV epithelial
      ovarian cancer impacts survival, a retrospective review of patients treated at
      the University of Pennsylvania Cancer Center (UPCC) from 1984 to 1995 diagnosed
      with Stage IV epithelial ovarian cancer was performed. Data were collected
      regarding grade, histology, reason for allocation to Stage IV, extent of surgery
      performed and residual disease at initial staging procedure, major perioperative
      complications, first-line chemotherapy regimen, length of inpatient hospital
      stay, outcome at second-look laparotomy, follow-up, and survival. For the
      purposes of this study, optimal cytoreduction was defined as a residual disease
      of 2 cm or less. Forty-seven patients with Stage IV epithelial ovarian cancer
      identified in the Society of Gynecologic Oncologists (SGO) Database at UPCC are
      included. Fourteen of 47 (30%) were optimally cytoreduced at the time of their
      staging procedure. Twenty-six of 47 (55%) were deemed Stage IV by virtue of
      positive pleural effusion cytology only. Twenty-one of 47 (45%) had
      intraparenchymal liver involvement or metastatic disease outside of the abdomen.
      The median survival of the suboptimally debulked group was 17 months, while
      median survival in the optimal group was 37 months (P = 0.0295). These data
      suggest that Stage IV epithelial ovarian cancer patients with less than 2 cm
      residual disease have a survival advantage over patients with greater than 2 cm
      residual.

PMID- 8995540
TI  - Stage IV ovarian cancer: impact of surgical debulking.
AB  - OBJECTIVE: To evaluate the influence of surgical debulking performed on patients
      with Stage IV ovarian cancer and to determine prognostic factors which identify
      pts who may benefit from aggressive initial surgical debulking. METHODS: A
      retrospective chart review was conducted (1/1/87-12/31/93). Eligible patients
      included all women with FIGO Stage IV ovarian cancer. Clinical information
      abstracted included age at diagnosis, histology type, tumor grade, criteria for
      Stage IV classification, surgical procedure performed, and tumor residuum.
      Optimal surgical status was defined as < or = 2 cm residual disease. Chemotherapy
      treatment was recorded, as was follow-up. Survival estimates were computed by
      Kaplan-Meier method with differences in survival calculated by the log-rank test.
      The Cox proportional hazards regression model was used to identify independent
      variables which were associated with an improved survival rate. RESULTS: One
      hundred five women were found in our database with Stage IV ovarian cancer and 97
      had complete information available. Median age of the patients was 57 years
      (range 24-81 years). Papillary-serous histology was found in 55/97 patients (57%)
      and 50 patients (52%) had grade 3 tumors. Forty-one of 97 patients (42%) had
      malignant pleural effusion and 20/97 (21%) had liver metastases. Ninety-two
      patients underwent a primary attempt at surgical debulking and 40/92 were
      optimally debulked. Twenty-one of 41 patients (51%) with pleural effusion were
      optimally debulked compared to 20/51 (39%) with other criteria for Stage IV
      disease (P = NS). Overall median survival was 21 months; optimally debulked
      patients' median survival was 40 months compared to 18 months for patients with
      bulky residual disease (P = 0.01). The survival advantage for optimally debulked
      patients was statistically significant for the two subgroups of patients with and
      without malignant pleural effusion. In the multivariate analysis only age less
      than 65 years and optimal debulking were independent predictors of outcome.
      CONCLUSIONS: Surgical debulking appears to be an important determinant of
      prognosis in women with Stage IV ovarian cancer, including patients with
      malignant pleural effusion.

PMID- 8995541
TI  - Prognostic significance of residual disease in patients with stage IV epithelial
      ovarian cancer.
AB  - PURPOSE: To evaluate the role of surgical debulking in patients with stage IV
      ovarian cancer. METHODS: We conducted a retrospective review of patients with
      advanced epithelial ovarian cancer treated at M. D. Anderson Cancer Center.
      Eligible patients included women with stage IV disease treated with platinum
      based chemotherapy. Surgical debulking was considered optimal if the diameter of
      the largest residual tumor was 2 cm or less. Survival analysis and comparisons
      were performed using the Kaplan-Meier method and the log-rank test. RESULTS: One
      hundred eight women with stage IV ovarian cancer were identified. The
      extraperitoneal metastatic sites were the liver parenchyma in 16 patients, the
      pleura in 54 patients, a variety of other organs in 22, and two or more sites in
      the remaining 16. Median age of the patient population was 58 years (range 35-81
      years). Surgery to reduce the primary tumor was performed in 100 patients. The
      procedures included salpingo-oophorectomy with or without hysterectomy in 94
      patients, omentectomy in 90, small bowel resection in 4, large bowel resection in
      23, and splenectomy in 2. At the completion of surgery, tumor reduction was
      considered optimal in 31 patients, suboptimal in 61, and undetermined in 8. The
      overall median survival for optimally debulked patients was 25 months compared to
      15 months for suboptimally debulked patients (P < 0.02). The progression-free
      survival, on the other hand, was not statistically different between the two
      groups. CONCLUSION: Residual tumor seems to be an important prognostic factor in
      patients with stage IV ovarian cancer. Surgical debulking may play a significant
      role in the treatment of these patients.

PMID- 8995542
TI  - In vitro antigene therapy targeting HPV-16 E6 and E7 in cervical carcinoma.
AB  - Human papillomavirus (HPV) infection is believed to play a central role in
      cervical carcinogenesis. Specifically, two viral oncoproteins, E6 and E7, possess
      transforming ability and have been shown to interact with the cellular tumor
      suppressors p53 and p105, the retinoblastoma (Rb) gene product. To test the
      hypothesis that E6 and E7 play an active role in the maintenance of the malignant
      phenotype and may be ideal targets for antigene therapy, we tested the
      antiproliferative effects of phosphorothioate oligodeoxynucleotides (oligos)
      targeting HPV-16 E6 and E7 in cervical cancer cell lines and primary tumor
      explants. The ATP cell viability assay was used to measure growth effects of 27
      mer antisense oligos targeting the ATG translational start region of HPV-16 E6
      and E7 sequences in HPV-16-positive cell lines SiHa and CaSki and four advanced,
      primary cervical tumor explants. A random oligo sequence, an HPV-18-positive and
      HPV-negative cell line, one histologically confirmed endometrial and two ovarian
      tumors were used as negative controls. HPV type was confirmed by hybrid capture
      techniques. Cell lines and sterile (staging laparotomy) tumor cells were plated
      at 5000 cells/0.1 ml and 100,000 cells/0.5 ml in 96-well plates or soft agar,
      respectively, and incubated at 37 degrees C with a single treatment of oligos at
      0-16 microM. E6/E7 combinations at a fixed ratio of 1:1 were used at 0-8 microM
      for each oligo. Cellular ATP was measured by luciferin/luciferase fluorescence on
      Day 6. HPV-16 E6 and E7 oligos showed antiproliferative effects in all HPV-16
      positive cell lines and primary tumor explants (IC50s 6.9-9.5 microM for cell
      lines, 9.1-12.1 microM primary cervical tumors), while the HPV-negative C33-A
      cell line and HPV-18-positive cell line HeLa were relatively insensitive to the
      HPV-16 oligos (IC50s > 30 microM extrapolated). The endometrial and two ovarian
      primary tumors were also insensitive to the HPV E6 and E7 oligos (IC50s > 25
      microM extrapolated). Random oligos had little effect on cell growth at
      concentrations up to 16 microM (< 25% inhibition), except in CaSki (@50%
      inhibition at 16 microM). Combinations of E6 and E7 demonstrated mixed
      synergistic and antagonistic effects as determined by combination indices (CI)
      derived from median effect parameters. In the HPV-16-positive primary cervical
      tumors and the cell line SiHa, E6/E7 combinations were synergistic at low doses
      (< 25% growth inhibitory dose range) and antagonistic at doses above this. For
      the HPV-16-positive cell line CaSki, however, E6/E7 combinations were
      antagonistic at all dose ranges. Phosphorothioate oligos directed against the
      viral oncogenes E6 and E7 were shown to have antiproliferative effects specific
      to HPV-containing cancer cells. These specific antiproliferative effects suggest
      that HPV-16 E6 and E7 sequences play an active role in the malignant growth
      properties of cervical cancer cells and may be ideal targets for antigene
      therapy.

PMID- 8995543
TI  - The expression patterns of standard and variant CD44 molecules in normal uterine
      cervix and cervical cancer.
AB  - CD44 is a cell-surface glycoprotein postulated to play a role in tumor-cell
      metastasis. We have examined the expression of the standard CD44 (CD44s), and
      alternative spliced variants of CD44 containing variant exons v6, v9, and v1O
      (CD44v6, CD44v9, and CD44v10 respectively) in 9 samples of normal cervix, 6
      samples of cervical intraepithelial neoplasia (CIN), and 11 samples with invasive
      cervical carcinomas. RT/PCR demonstrated the presence of CD44s in all samples of
      normal cervix and those with invasive carcinomas. CD44v6 was also found in all
      normal cervical samples and in 9 tissue samples of invasive carcinomas. The
      results also suggested that some tumor specimens had several higher molecular
      transcripts containing exon v6 compared to specimens of normal cervix.
      Immunohistochemistry detected the presence of CD44s and the absence of CD44v10 in
      both epithelial and stromal cells in all specimens. In contrast, CD44v6 and
      CD44v9 were stained positive in epithelial cells but were absent in stromal
      cells. The intensity of CD44v6 and CD44v9 staining was strongest in normal
      cervical epithelium followed by CIN, invasive squamous cell carcinoma, and
      adenocarcinoma. In the malignant samples, heterogeneity in staining intensity
      among different clusters of tumor cells was observed. Furthermore, poorly
      differentiated and undifferentiated carcinomas from patients having poor
      prognosis did not stain at all. This study suggests that variant CD44 molecules
      may serve an important function in the cell contact of cervical epithelial cells,
      and that cervical epithelium acquires heterogeneity in the expression of CD44
      adhesion molecules during carcinogenesis, which may be related to tumor
      metastasis.

PMID- 8995544
TI  - Improvement of diagnostic accuracy of transvaginal ultrasound for identification
      of endometrial malignancies by using cutoff level of endometrial thickness based
      on length of time since menopause.
AB  - Transvaginal ultrasonography (TVS) is considered useful for identifying
      endometrial malignancies, but it has a low specificity and a high false-positive
      rate. The purpose of this study was to improve the specificity of this technique.
      A total of 300 postmenopausal women were studied. They were clinically evaluated
      by TVS and endometrial histology. Twenty women yielded pathologic findings on
      endometrial examination. The mean endometrial thickness was related to the length
      of time since menopause. For endometria with pathological findings, sonographic
      measurements of endometria with a thickness of greater than 3 mm exhibited 95.0%
      sensitivity, 68.5% specificity, 19.4% positive predictive value, and 99.4%
      negative predictive value. If a 4-mm cutoff limit was used for < 5 years since
      menopause and a 3-mm cutoff limit was used for > or = 5 years since menopause,
      95.0% sensitivity, 78.1% specificity, 25.7% positive predictive value, and 99.5%
      negative predictive value were obtained. The specificity and false-positive rate
      were improved when the cutoff limit was decided based on the length of time since
      menopause. The cutoff level of the endometrial thickness for detection of
      endometrial malignancies should be decided based on the length of time since
      menopause.

PMID- 8995545
TI  - Early occurrence and prognostic significance of p53 alteration in primary
      carcinoma of the fallopian tube.
AB  - The pathogenesis of primary carcinoma of the fallopian tube (PCFT) is poorly
      understood. Tumor suppressor p53 gene alterations are common in human
      malignancies, but their role in the tumorigenesis and survival of PCFT is
      undefined. The objectives of this study were to define the occurrence and
      prognostic role of p53 alteration in PCFT and to examine the efficiency of
      immunohistochemistry (IHC) in detecting p53 alteration in PCFT. Fifty-two PCFT
      and 10 normal fallopian tubes were examined for p53 alteration by IHC and
      polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The
      Kaplan-Meier method was used to derive the survival function, while the log-rank
      test was used to compare curves for two or more groups. Other patients'
      characteristics were analyzed by two-tailed Fisher's exact tests. IHC correlated
      well with PCR-SSCP with 100% sensitivity and 83.3% specificity for detecting p53
      alteration in this study. Thirty-one of 52 (57%) PCFT showed p53 alteration.
      Alteration of p53 occurred in all stages of PCFT with a similar incidence in
      carcinoma in situ and late-stage disease. Alteration of p53 was related to tumor
      histologic type. Significant survival difference was noted between advanced and
      early clinical stages but no such difference was identified among different tumor
      grades. Compared to the p53-nonaltered group, the presence of p53 alteration in
      PCFT was related to significantly decreased patient survival (RR = 6.8, 95% CI =
      2.9-16.2) in multivariate analysis. In the subgroup of patients with residual
      tumor after surgery, those with p53-altered tumors had a significantly decreased
      survival compared to those with p53-nonaltered group (RR = 7.4, 95% CI = 1.9
      28.2). Alteration of p53 is common and IHC is an efficient method to detect p53
      alteration in PCFT. Shorter survival is associated with p53 alteration which is
      an independent marker for the disease in this study. Alteration of p53 may be an
      early event in tubal tumorigenesis and may play an important role in the
      development of PCFT. Whether detection of p53 alteration may serve as an
      indicator of high-risk patients for whom more aggressive adjuvant chemotherapy
      may be considered needs to be explored in the future.

PMID- 8995546
TI  - Laparoscopic surgical staging in cervical cancer--preliminary experience among
      Chinese.
AB  - BACKGROUND: With the availability of modern laparoscopic equipment and the
      ability to perform advanced operative procedures, there are a growing number of
      circumstances under which operative laparoscopy is applicable to patients with
      gynecologic malignancies. METHODS: From May 1992 to December 1995, a total of 67
      patients with cervical carcinoma of different FIGO stages underwent pretreatment
      evaluation of pelvic or para-aortic lymph node status by means of laparoscopic
      dissection. Four patients with FIGO stage Ia2 and 35 patients with FIGO stage Ib
      cervical carcinoma received pelvic lymphadenectomy of the external iliac,
      internal iliac, and the obturator regions; the rest of the 28 patients with
      advanced FIGO stages had para-aortic lymphadenectomy only. Of these advanced
      cases, 15 patients were FIGO stage IIb, 8 were FIGO stage IIIa, and 5 were FIGO
      stage IIIb. All cases were followed up from 6 to 40 months. RESULTS: All the
      patients tolerated the procedures smoothly except one patient with incomplete
      procedure due to bleeding from vena cava. In pelvic lymphadenectomy cases, an
      average of 14.2 nodes from the right side and 12.5 nodes from the left side were
      removed through laparoscope, and in para-aortic lymphadenectomy cases, an average
      of 8 lymph nodes was removed from both sides of para-aortic area. Five of the 39
      pelvic lymphadenectomy patients showed positive involvement of the obturator
      nodes and they were later put on the radiation therapy. The other 34 patients
      with no pelvic lymph node metastasis underwent radical surgery 2 days later or
      followed immediately by laparoscopic-assisted vaginal radical hysterectomy. No
      more positive nodes were found. Among the advanced cervical cancer patients, 4 of
      the stage IIb patients, 3 of the stage IIIa patients, and 3 of the stage IIIb
      patients showed positive para-aortic lymph node involvement and these patients
      were put on adjuvant chemotherapy and whole pelvic irradiation or extended field
      irradiation only. For the remaining 18 patients without para-aortic node
      involvement, only whole pelvic irradiation was offered. Macroscopic invasion of
      the para-aortic lymph nodes was detected in only 57% of the patients by computed
      tomography. CONCLUSIONS: This preliminary experience showed that laparoscopic
      pelvic or para-aortic lymphadenectomy was an efficient and feasible surgical
      staging procedure in the pretreatment evaluation of carcinoma of the uterine
      cervix and elaborates the rationale for the management of cervical cancer.

PMID- 8995547
TI  - Predictors of distant recurrence in clinical stage I or II endometrial carcinoma
      treated by combination surgical and radiation therapy.
AB  - A retrospective analysis of 201 patients with clinical Stage I or II endometrial
      carcinoma treated by combined surgery and radiation therapy from January 1976 to
      December 1992 is reported. The aim of the study was to determine predictors, if
      any, for distant recurrence. Twenty-eight patients (13.9%) in our series
      developed a recurrence. The most common sites were peritoneal carcinosis (28.6%),
      bones (28.6%), and lungs (21.4%). Seventy-eight percent appeared within 3 years,
      and actuarial survival rates at 12, 36, and 60 months after recurrence were 39.2,
      14.2, and 7.1%, respectively. An analysis of predictive factors significant for
      the development of distant recurrence was performed. Significant factors by
      univariate analysis were age (P = 0.019), stage (P = 0.02), grade (P = 0.014),
      depth of myometrial invasion (P = 0.007), lymph node involvement (P < 0.001), and
      peritoneal cytology (P = 0.006). A multivariate analysis of these variables
      showed that lymph node involvement was the strongest predictor for distant
      recurrence.

PMID- 8995548
TI  - Cervical cancer in young women in Taiwan: prognosis is independent of
      papillomavirus or tumor cell type.
AB  - The objective of this study was to address the hypotheses that younger patients
      with cervical cancer have a uniquely worse clinical outcome and/or are more
      likely to have adverse tumor cell types or specific human papillomaviruses (HPV).
      Cases of stage Ib-IIa cervical cancer among women 35 years of age or younger (82)
      and over 35 (54) were analyzed and compared with respect to the following: (1)
      histologic type (squamous vs nonsquamous), (2) human papillomavirus (HPV) type
      via polymerase chain reaction, and (3) clinical parameters, including tumor size,
      nodal metastases, and recurrence/persistence. Patients 35 years of age or younger
      had a survival similar (71.2% vs 72.4%) to that of older women from the same
      institution. In the younger group, outcome was not correlated with the presence
      or absence of HPV or HPV type. Nonsquamous carcinomas, including adenocarcinoma
      and small cell carcinoma, were strongly associated with HPV18, were more
      prevalent in the younger group, and had a slightly higher risk of
      recurrence/persistence; however, these differences were not significant and 71%
      of the recurrences were squamous cell carcinomas. Thus, in young Taiwanese women
      with stage Ib-IIa cervical cancer, the majority of deaths cannot be attributed to
      a specific HPV type or unique tumor morphology.

PMID- 8995549
TI  - Serum inhibin and disease status in women with ovarian granulosa cell tumors.
AB  - OBJECTIVE: To determine if immunoreactive inhibin assayed in serum from women
      with granulosa cell tumors correlated with tumor burden, reflected response to
      treatment, or predicted recurrent disease. STUDY DESIGN: Serum samples were
      collected following bilateral oophorectomy (BSO) with or without other indicated
      surgery in 15 patients with granulosa cell tumors. Inhibin radioimmunoassay (RIA
      Inh) was performed on all samples and results were correlated with tumor burden,
      disease status, and treatment response. RESULTS: Fifteen patients had serum
      assayed for inhibin with levels ranging from 0 to 7470 U/liter. In 4 patients
      with measurable recurrent disease, inhibin levels correlated directly with tumor
      burden (r2 = 0.96). Four patients had serum drawn during clinical remission and
      in all 4 patients elevated inhibin levels predated recurrence by a median
      interval of 11.5 months (range 7-20). The remaining 7 were treated for primary
      disease and were in clinical remission with a median follow-up of 33 months
      (range 9-53). Four of these 7 patients were surgically staged: 2 were FIGO Stage
      I and inhibin levels fell to 0 U/liter; 2 patients had metastatic disease (Stage
      IIc and IIIa) and their inhibin levels were found to be elevated following
      complete resection. The remaining 3 were not surgically staged, and all had
      elevated inhibin levels while in clinical remission, suggesting occult disease.
      Of the 15 total patients, 1 who was treated with chemotherapy for recurrent
      disease was followed with serial inhibin levels. She showed a complete response
      to therapy with inhibin levels falling from 975 to 0 U/liter with 15 months
      follow-up. CONCLUSIONS: Serum inhibin levels reflect tumor burden and may be
      valuable in assessing response to chemotherapy or predicting recurrent disease in
      women with granulosa cell tumors who have had BSO. Serum inhibin level evaluation
      should be incorporated into large-group trials of therapy for granulosa cell
      tumors.

PMID- 8995551
TI  - Management of gynecologic oncology patients with a preoperative deep vein
      thrombosis.
AB  - Our experience with gynecologic oncology patients presenting preoperatively with
      a deep vein femoral thrombosis is reported. Over a 3-year period data were
      collected on all patients at the University of South Florida (USF) requiring
      surgery for a known or suspected gynecologic cancer and having a concomitant
      active femoral venous thrombosis. Twelve such patients were managed. Management
      was divided among three options: heparinization, preoperative inferior vena cava
      (IVC) filter, and intraoperative IVC ligation. For two patients a filter could
      not be placed preoperatively due to tumor compression of the IVC. Both underwent
      IVC ligation intraoperatively. One of the two died intraoperatively, possibly
      related to pulmonary embolism. One of eight with a preoperative IVC filter had
      obvious clot propagation postoperatively, managed with heparin. One of two
      managed with heparin only had severe bleeding and heparin-associated
      thrombocytopenia (HAT) preoperatively. Based on our experience and a review of
      the literature, we recommend therapeutic heparinization and a preoperatively
      placed IVC filter for most preoperative gynecologic oncology patients with
      femoral deep venous thrombosis.

PMID- 8995550
TI  - Photodynamic therapy using topically applied dihematoporphyrin ether in the
      treatment of cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To perform a phase I study of topically applied dihematoporphyrin
      ether (DHE) in the photodynamic treatment (PDT) of cervical intraepithelial
      neoplasia (CIN) using fixed DHE doses and application schedules, and a variable
      dose of 630 nm red light delivered by an argon-pumped dye laser. METHODS: Between
      February 1993 and April 1994, 24 nonpregnant women with a histologic diagnosis of
      CIN were enrolled. All patients had lesions involving at least 25% of the cervix
      that were colposcopically visible. Using a cervical cap, 2 ml of a 1% solution of
      DHE (Photofrin) in a 4% Azone and isopropyl alcohol vehicle were applied to the
      cervix 24 hr prior to PDT. An argon-pumped dye laser providing light at 630 nm
      was then used to perform PDT. Light was coupled into a 400-microm silica fiber
      optic terminating in a microlens which focused the laser radiation onto a
      circular field of uniform light intensity perpendicular to the tissue. The entire
      ectocervix was treated in a single field including a margin of 3-5 mm of normal
      cervix. Using a constant power density (150 mW/cm2) to avoid thermal injury, the
      PDT energy was increased every 4 patients in a phase I fashion (40, 60, 80, 100,
      120, and 140 J/cm2). RESULTS: Thirteen patients with CIN I, 7 patients with CIN
      II, and 4 patients with CIN III were treated. The maximal energy density was well
      tolerated. Toxicity was minimal with no patients experiencing local necrosis,
      sloughing, or scarring; however, a mild vaginal discharge was noted in several
      patients. Systemic effects were absent. After 12 months of follow-up at 3-month
      intervals, 22 patients are evaluable of whom 15 (68%) are disease free. One
      patient was lost to follow-up and in another the cervical cap was dislodged. Four
      of the 7 failures or recurrences occurred at energy densities of 80 J/cm2 or
      less, while 8 of 11 (73%) patients were treated successfully with PDT at an
      energy density of 100 to 140 J/cm2. CONCLUSIONS: PDT with DHE and an argon-pumped
      dye laser at 630-nm wavelength delivering an energy density of 140 J/cm2 is safe
      and effective in treating CIN. Phase II studies using PDT at the prescribed
      application schedule and dose are indicated.

PMID- 8995552
TI  - A randomized trial of paracentesis plus intraperitoneal tumor necrosis factor
      alpha versus paracentesis alone in patients with symptomatic ascites from
      recurrent ovarian carcinoma.
AB  - PURPOSE: Previous phase I and II studies of intraperitoneal recombinant human
      tumor necrosis factor-alpha (rhTNF-alpha) suggested a high degree of efficacy in
      reducing or eliminating ascitic fluid. To more accurately determine the efficacy
      of this agent, the role of paracentesis versus paracentesis plus intraperitoneal
      rhTNF-alpha was studied in a randomized trial. PATIENTS AND METHODS: Thirty-nine
      patients with symptomatic ascites with a volume of > 1000 ml from recurrent
      epithelial ovarian carcinoma or primary peritoneal carcinoma, which was
      refractory to standard therapy, were randomized either to receive 0.06 mg/m2
      rhTNF-alpha (Knoll, Canada) (the dose determined optimal from phase I and II
      studies) intraperitoneally after drainage of fluid or to receive drainage alone.
      A maximum of three treatments were given at weekly intervals. Eighteen patients
      were randomized to receive rhTNF-alpha. RESULTS: None of 18 evaluable rhTNF-alpha
      patients had either a complete response (CR) (no clinical evidence of ascites and
      < 400 ml of fluid on ultrasound) or a partial response (PR) (asymptomatic ascites
      and < or = 1000 ml of fluid ultrasound). There were no CRs or PRs in the 17
      evaluable patients who received drainage alone. The intraperitoneal infusion of
      rhTNF-alpha was generally well tolerated. Moderate to severe toxicity consisted
      of pain/discomfort in 42.1%, fever/chills in 36.9%, nausea/vomiting in 10.5%,
      edema in 10.5%, and hypotension in 5.3% of patients receiving rhTNF-alpha.
      CONCLUSION: rhTNF-alpha, as given in this study, was not effective in preventing
      recurrence of ascites in this patient population.

PMID- 8995553
TI  - DNA ploidy and expression of p53 and C-erbB-2 in extramammary Paget's disease of
      the vulva.
AB  - Clinical data were retrieved from the hospital records of 34 patients with
      Paget's disease of the vulva treated from 1972 to 1990. Flow-cytometric (FCM) DNA
      measurements and p53 and c-erbB-2 immunostaining were performed on paraffin
      embedded samples. Five patients had an underlying adenocarcinoma and 29
      intraepithelial disease (IEP). Twenty-seven patients with IEP underwent surgery.
      The surgical margins were positive in 15 patients, negative in 10, and not
      evaluable in 2. The tumor was diploid in 15 patients, nondiploid in 11, and not
      evaluable in 1. Eight patients recurred, 6/15 (40%) with positive and 2/10 (20%)
      with negative margins. One patient with positive margins was never disease-free.
      Recurrence was seen in 6/11 (55%) patients with nondiploid tumors, 4 with
      positive and 2 with negative margins. Two of 15 (13%) patients with diploid
      tumors recurred/persisted, both with positive margins. None of the 6 patients
      with diploid tumors and negative margins recurred. p53 and c-erbB-2 were found
      negative in all but 4 patients. Tumor nondiploidy was associated with an
      increased risk of recurrence irrespective of surgical radicality. p53 and c-erbB
      2 seemed to play no role in the pathogenesis or prognosis.

PMID- 8995555
TI  - Steroid release from two human epithelial ovarian tumors: evidence for an
      intrinsic production in vitro.
AB  - Tissue specimens from the primary tumor and metastasis (histological examination:
      cystadenocarcinoma) of two postmenopausal women were cut into pieces and were
      incubated or superfused for 3- to 4-hr periods. The incubation and superfusion
      procedures were performed in the absence and presence of human chorionic
      gonadotropin (hCG, 10 IU/ml). After incubation, the medium concentrations of
      progesterone (P), testosterone (T), androstendione, and 17beta-estradiol (E2)
      were determined by radioimmunoassay, while after superfusion the medium
      concentrations of cyclic AMP (cAMP), P, T, and E2 were analyzed. HCG stimulated
      the production of cAMP in the superfused tissue of the first case and in the
      second case the addition of hCG to the incubation medium caused a significant
      drop in testosterone release by the primary tumor and in androstendione release
      by the metastasis. These results suggest that tissues from primary tumor and
      metastasis were capable of releasing steroids into the media, supporting the
      contention that tissue from epithelial ovarian cancers can produce and/or release
      steroids in its own right.

PMID- 8995554
TI  - Detection of p53 point mutations in primary human vulvar cancer by PCR and
      temperature gradient gel electrophoresis.
AB  - Clinical and experimental evidence is consistent with a key role of point
      mutations of the p53 tumor suppressor gene in the etiology of squamous cell
      carcinoma. To determine the relation of tumor behavior and patient survival in
      vulvar cancer in regard to p53 status, we retrospectively analyzed 38 paraffin
      embedded specimens of primary vulvar cancer for genetic alterations of exons 5-8
      of the p53 gene. For detection of p53 point mutations we used in vitro
      amplification by polymerase chain reaction (PCR) and temperature gradient gel
      electrophoresis (TGGE) and, as a detection method, direct sequencing for mutation
      verification. p53 point mutations were detected in 12/38 tumor specimens.
      Patients bearing p53 point mutations showed a significantly shorter relapse-free
      (log-rank test, P = 0.002) and overall survival time (log-rank test, P = 0.0006).
      We conclude that PCR-TGGE is an appropriate method for detection of p53 point
      mutations in paraffin-embedded material. We show that loss of wild-type p53 is an
      adverse prognostic factor in patients suffering from vulvar cancer.

PMID- 8995556
TI  - Ovarian volume in postmenopausal breast cancer patients treated with tamoxifen.
AB  - BACKGROUND: Postmenopausal breast cancer patients treated with tamoxifen have
      been found to have a high incidence of ovarian tumors. Transvaginal
      ultrasonography is an accurate and reliable method for measuring ovarian size.
      The purpose of this study was to establish normal values for basal ovarian volume
      in postmenopausal tamoxifen-treated patients and compare them with those
      established for healthy, postmenopausal women in the same population with no
      exposure to hormone treatment. METHODS: In a prospective open pilot study, the
      ovaries of 65 postmenopausal breast cancer patients treated for at least 6 months
      with tamoxifen were measured by transvaginal ultrasonography. From the same
      population, 311 healthy postmenopausal women with no exposure to hormone therapy
      were examined and served as controls. After matching for menopausal age, ovarian
      volume was compared between groups. RESULTS: Mean ovarian volume of
      postmenopausal tamoxifen-treated patients was persistently low through the
      menopause, whereas the mean ovarian volume of the controls was large, gradually
      decreasing up to the 10th menopausal year (8.6 +/- 2.3 and 2.8 +/- 2.1 cm3,
      respectively). Mean ovarian volume of the tamoxifen-treated patients was
      significantly lower than that of the controls during the initial menopausal
      years. CONCLUSIONS: An ovarian volume that is considered within normal range for
      a specific menopausal age in a healthy postmenopausal woman is abnormal for a
      postmenopausal tamoxifen-treated patient.

PMID- 8995557
TI  - Taxol as second-line treatment in patients with advanced ovarian cancer after
      platinum-based first-line chemotherapy.
AB  - Salvage chemotherapy in platin-resistant patients typically results in low
      response rates and short survival, therefore new active cytotoxic agents must be
      found. One of these agents is paclitaxel (Taxol), isolated from the bark of the
      western yew which acts as an antimicrotubule agent. In our study 28 patients were
      treated with Taxol, 20 of whom had platinum-resistant tumors. Taxol was
      administered at a starting dose of 175 mg/m2, infused over 3 hr every 21 days. A
      total of 145 courses of Taxol was infused. Dexamethasone, diphenhydramine, and
      ranitidine were given as premedication. The response rate was 25% (3 complete and
      4 partial remissions), the median survival duration was 15 months. In contrast to
      other studies we found a lower response rate in patients resistant to platinum
      based therapy: 15% (no complete, 3 partial remissions). The most common severe
      toxicity was leukopenia, with grade 3 toxicity occurring in 10% of the courses;
      no grade 4 leukopenia or neutropenia was noted. Neurologic toxicity was a
      clinically significant adverse effect, with 1% of patients experiencing grade 3,
      9% experiencing grade 2, and 3% experiencing grade 1 toxicity. Other adverse
      effects were less frequent and less severe. We conclude that paclitaxel, which in
      a prospective randomized trial has been shown to be the most active treatment of
      advanced ovarian cancer, yields low response rates in platinum-resistant
      patients. Only a few of them profited from second-line treatment with Taxol. This
      could be a new aspect in the treatment of platinum-resistant ovarian cancer with
      Taxol.

PMID- 8995558
TI  - Identification of LDH-ras p21 protein complex and expression of these genes in
      human ovarian cancer.
AB  - Normal ovarian and ovarian cancer tissues from 35 patients were tested for LDH-A
      ras protein complex formation, as well as for the expression of ras and LDH-A
      genes. By immunodetection of the immunoprecipitates, LDH-A-ras protein complexes
      are present in the homogenates of human ovarian tissues (benign and malignant).
      Two bands of 21 and 36 kDa were demonstrated in affinity-purified LDH active
      fractions by Western blot analysis, and these two proteins were proved to be ras
      p21 and LDH-A by immunodetection. By Northern blot analysis, elevated levels of c
      Ki-ras and LDH-A mRNA transcripts were noted in 49% (17/35) and 40% (14/35) of
      ovarian cancers, respectively. Concurrent high expression of both genes was
      demonstrated in 11 cases (31%). Tyrosylphosphorylation of LDH-A was demonstrated
      in normal and malignant ovarian tissues, and the extent of phosphorylation was
      correlated with the stage of ovarian cancer. The concurrent elevated expression
      of ras and LDH-A in the same ovarian tissue may imply that the increased
      synthesis of LDH-A is due to increased or amplified signaling of the ras-cascade
      pathway. The possible biochemical role of the tyrosylphosphorylated LDH-A
      complexed with ras p21 in cell transformation and progression of human ovarian
      cancer is worthy of further investigation.

PMID- 8995559
TI  - Parity as an independent prognostic factor in malignant mixed mesodermal tumors
      of the endometrium.
AB  - Malignant mixed mesodermal tumors (MMMT) are the most malignant neoplasms known
      to occur in the uterus. The most important prognostic factors are the extent of
      tumor at diagnosis, depth of myometrial invasion, and, as regarded by some
      authors, the sarcomatous component. We report on a retrospective analysis in 83
      patients with MMMT. By univariate analysis survival was dependent on stage, depth
      of myometrial invasion, kind of therapy, age at menopause, and parity. However,
      the sarcomatous component did not significantly influence survival. Using the
      multivariate Cox regression analysis stage and parity or depth of myometrial
      invasion and parity were found to independently predict prognosis. Despite an
      interval of more than 20 years from the last childbirth to tumor appearance a
      beneficial influence of parity on the prognosis of MMMT was identified. This is
      unique in oncology. Especially patients with more than three children formed a
      subgroup of long-term survivors. It is interesting to note that parity was found
      by means of a Cox regression analysis to be statistically independent, and no
      correlation with other classical prognostic factors was detected.

PMID- 8995560
TI  - A phase II study of leuprolide in advanced/recurrent endometrial cancer.
AB  - In order to determine the efficacy and toxicity of the gonadotrophin-releasing
      hormone agonist Leuprolide in the management of patients with recurrent or
      metastatic endometrial cancer, we performed a phase II study. Patients were
      included if there was clinical or radiological documentation of bidimensionally
      measurable recurrent or metastatic endometrial cancer that was deemed incurable.
      Treatment was 7.5 mg i.m. every 28 days, and was to continue for at least 2
      courses until evidence of disease progression, patient requested withdrawal, or
      unacceptable toxicity. Twenty-five patients received Leuprolide for recurrent or
      metastatic endometrial cancer. The median age at study entry was 62 years, and
      the median time from initial diagnosis to first course of Leuprolide was 25
      months. Six patients had received no systemic or radiotherapy prior to study
      entry, and 2 of these had not previously undergone hysterectomy. Fifteen patients
      received prior pelvic radiotherapy and 3 patients received prior whole abdominal
      radiotherapy. Nine of the 25 patients had received prior progestational agents,
      and 2 had received prior systemic chemotherapy. There were no responders, 8
      patients had stable disease for a median 5 months (range 1-8), 14 patients
      progressed on therapy, and 3 patients were not evaluable for response due to
      receiving only 1 treatment. One patient experienced a grade 3 toxicity that was
      possibly attributable to Leuprolide (deep venous thrombosis). The median survival
      from study entry was 6 months. Twelve patients received progesterone after
      discontinuing this study, and none responded. Leuprolide does not appear to be a
      clinically active agent in the treatment of recurrent or metastatic endometrial
      cancer.

PMID- 8995562
TI  - Prognostic value of peritoneal cytology in patients with carcinoma of the uterine
      cervix.
AB  - Peritoneal cytology was obtained in 374 patients with carcinoma of the uterine
      cervix (stage IB-IIB) in whom gross intraperitoneal disease was absent at the
      time of radical hysterectomy and node dissections. The relevance of positive
      peritoneal cytology in relation to the cell type of the tumor was examined. An
      exceedingly small rate of peritoneal cytologic positivity was found in patients
      with squamous cell carcinoma (1.7%, 4/242). One of the four patients with
      positive cytology developed a lung recurrence. On the other hand, the incidence
      of positive peritoneal cytology in patients with adenocarcinoma and adenosquamous
      carcinoma was 11.4% (15/132). The 3-year disease-free survival rate in patients
      having adenocarcinoma and adenosquamous carcinoma with positive peritoneal
      cytology was 57.8%, while it was 80.7% in patients with negative peritoneal
      cytology. However, this factor was closely associated with other adverse
      prognostic factors. A multivariate analysis revealed that positive peritoneal
      cytology was not an independent prognostic factor in patients with adenocarcinoma
      and adenosquamous carcinoma. In addition, intraperitoneal recurrence was not
      correlated with the presence of cancer cells in the peritoneal fluid. The series
      indicates that peritoneal cytology in cervical cancer is of little value in
      treatment planning.

PMID- 8995563
TI  - Significance of a single CA 125 assay combined with ultrasound in the early
      detection of ovarian and endometrial cancer.
AB  - We evaluated the utility of a single CA 125 measurement in combination with
      transvaginal sonography for early detection of ovarian and endometrial cancer in
      asymptomatic postmenopausal women. A sample of peripheral blood was taken from
      1291 apparently healthy postmenopausal women, who were examined by conventional
      and color Doppler ultrasound for early detection of ovarian and endometrial
      cancer. Serum CA 125 was determined in all samples 3 years later by the IMx CA
      125 assay (Abbott Laboratories, Abbott Park, IL). The cutoff level based on the
      99th percentile was 30 U/ml. Elevated values were controlled by repeat sonography
      and an additional determination of CA 125. Record linkage with the files of the
      Finnish Cancer Registry was performed 3 1/2 years after the primary sonographic
      screening. The mean CA 125 concentration was 8.1 U/ml (range 0-1410 U/ml).
      Fourteen of the 1291 women had a CA 125 level greater than 30 U/ml. None of these
      had signs of either endometrial or ovarian malignancy in the primary sonography
      screening. Among the other women three cases of endometrial carcinoma (all stage
      Ib) and one ovarian carcinoma (stage Ia with borderline malignancy) were detected
      by sonography. All these patients had a CA 125 value <30 U/ml, the mean value
      being 11.4 U/ml (range 7.5-16.7 U/ml). During follow-up of 3.5 years, one stage
      Ia ovarian carcinoma, one abdominal carcinomatosis, and two endometrial
      carcinomas (both stage Ib) were diagnosed. In these patients the mean value for
      CA 125 was 12.7 U/ml (range 2.5-30.9 U/ml) at the primary sonography screening. A
      single CA 125 measurement provides no advantage in the early detection of ovarian
      and endometrial cancer in asymptomatic postmenopausal women compared with
      transvaginal sonography. The vast majority of women with an elevated CA 125 value
      have some reason other than an ovarian or endometrial malignancy for this
      finding.

PMID- 8995561
TI  - Pelvic exenterations: supralevator, infralevator, and with vulvectomy.
AB  - The purpose of this study was to determine whether the different types (I, II,
      and III) of pelvic exenterations have prognostic implications in regard to
      operative features, postoperative complications, and survival. The records of the
      133 patients who underwent pelvic exenteration at the Mayo Clinic from 1977 to
      1986 were reviewed. The records were abstracted for duration of hospitalization,
      febrile morbidity, duration of operation, operative blood loss, number of blood
      transfusions, performance of a perineal phase, development of an omental carpet,
      vaginal reconstruction, reoperation, additional tissue resection, complications,
      and survival. Statistically significant differences were noted univariately
      between types I, II, and III in regard to the development of an omental carpet,
      whether or not vaginal reconstruction was done, the performance of a perineal
      phase, the resection of additional tissues, and the duration of hospitalization.
      The operative and postoperative morbidity and survival were not influenced
      significantly by the type of exenteration. The subclassification of the
      exenteration groups into type I (supralevator), type II (infralevator), and type
      III (with vulvectomy) is helpful to facilitate understanding of the extent of
      resection of the pelvic structures and the anatomical changes associated with
      each operation. Subgrouping facilitates communication, not only between pelvic
      surgeons but also with third-party payers.

PMID- 8995564
TI  - Adenocarcinoma of the uterine cervix with predominantly villogladular papillary
      growth pattern.
AB  - We reviewed the clinical and pathological features of seven cases of
      adenocarcinoma of the uterine cervix with predominantly villogladular papillary
      growth pattern. The patients, who ranged in age from 33 to 54 (mean, 45) years,
      underwent radical hysterectomy. In all seven cases, the tumors were papillary
      exophytic architecture lined by stratified epithelial cells with mild to moderate
      nuclear atypicality. In one of seven cases, the majority of the tumor showed
      villogladular papillary component, but the small foci of small cell carcinoma was
      present in the endocervical end of the tumor. The lymph vascular invasion was
      demonstrated in two of seven cases, and these two had pelvic lymph node
      metastases. One of these two patients had recurrence 30 months after the initial
      treatment and died of disease after 46 months. The follow-up ranged from 9 to 169
      (median, 46) months. The presence or absence of lymph vascular invasion and minor
      components of this tumor such as small cell carcinoma, serous cell carcinoma, and
      clear cell carcinoma with a poor prognosis may be important histological findings
      before deciding to manage this tumor by the conservative treatment.

PMID- 8995565
TI  - Management of cervical intraepithelial neoplasia during pregnancy with LOOP
      excision.
AB  - OBJECTIVE: Management of severe cervical dysplasia/possible microinvasive
      carcinoma during pregnancy is frequently associated with significant morbidity.
      The purpose of this study is to determine the efficacy of LOOP excision performed
      during pregnancy, and also to record the nature and frequency of complications of
      the procedure. METHODS: Twenty women underwent LOOP excision during pregnancy.
      The gestational age range was 8-34 weeks. Data concerning indications,
      complications, and histopathologic results were recorded. RESULTS: Fourteen of 20
      (70%) had dysplastic changes in the LOOP specimen. Eight of 14 (57%) had involved
      margins. Nine of 19 (47%) had residual dysplasia 3 months postpartum, including 3
      patients whose initial LOOP specimens were negative for dysplasia. Significant
      morbidity included 3 preterm births, 2 patients who required blood transfusion
      following LOOP, and 1 unexplained intrauterine fetal demise documented 4 weeks
      post-LOOP. The gestational age range of those patients who had significant
      morbidity was 27-34 weeks. CONCLUSIONS: LOOP excision of the cervix during
      pregnancy does not consistently produce diagnostic specimens and is associated
      with a significant rate of residual disease. Morbidity appears similar to that of
      cone biopsy during pregnancy and occurs primarily when the procedure is performed
      in the third trimester. Until refinements in technique occur, LOOP excision
      during pregnancy should be reserved for limited indications.

PMID- 8995566
TI  - The management of gestational trophoblastic tumors with etoposide, methotrexate,
      and actinomycin D.
AB  - OBJECTIVE: To evaluate the efficacy and safety of etoposide, methotrexate, and
      actinomycin D (EMA) as primary and secondary therapy for gestational
      trophoblastic tumor (GTT). METHODS: In a retrospective study, the medical records
      of all patients with middle-risk metastatic GTT or nonmetastatic choriocarcinoma
      receiving primary EMA and patients with GTT resistant to single-agent regimens
      treated with secondary EMA were reviewed. Hematologic toxicity was graded using
      WHO criteria. RESULTS: Seven patients received primary EMA with 5 (67%) achieving
      remission. Twenty-two patients with resistance to single-agent regimens received
      secondary EMA with 21 (95%) achieving remission. The most acute hematologic
      toxicity was grade 1 or 2. Only 2 of 90 EMA cycles were associated with grade 4
      toxicity requiring hospital admission. CONCLUSION: Although EMA effectively
      induces remission with minimal acute hematologic toxicity in the primary and
      secondary therapy of GTT, recently published data regarding secondary tumors
      associated with etoposide exposure should restrict its use to patients who
      absolutely require etoposide to achieve remission.

PMID- 8995567
TI  - Cisplatin-based chemotherapy in the management of germ cell tumors of the ovary:
      The Institut Gustave Roussy Experience.
AB  - The past two decades have seen great improvements in the diagnosis and management
      of ovarian germ cell tumors. To assess the impact of cisplatin-based
      chemotherapy, a retrospective review based on a standardized questionnaire was
      conducted in 54 patients with malignant germ cell neoplasms of the ovary who
      received cisplatin-based chemotherapy as part of their first-line or salvage
      therapy at the Institut Gustave Roussy from September 1980 to December 1992.
      Chemotherapy was administered as primary postoperative treatment in 40 (75%)
      patients while 14 patients received chemotherapy as part of their salvage
      treatment for recurrent disease. With a median follow-up of 6 years, the overall
      survival is 74%. Twenty-three (96%) of the 24 patients who received chemotherapy
      in an adjuvant setting are alive without evidence of disease compared to 9 (56%)
      of 16 and 8 (57%) of 14 who were treated for advanced or recurrent disease,
      respectively. The long-term toxicity was minimal. Among 22 patients who underwent
      conservative surgery, 13 resumed normal menstrual function. Four patients
      delivered 5 healthy children. With male germ-cell tumors as a template, cisplatin
      based chemotherapy clearly improves the prognosis for patients with ovarian germ
      cell tumors, especially in the adjuvant setting.

PMID- 8995568
TI  - A clinicopathologic study of glandular dysplasia of the cervix.
AB  - With the increasing incidence of cervical adenocarcinoma there is a growing
      interest in the detection and treatment of glandular precursors. A major obstacle
      to this research is that endocervical glandular dysplasia (EGD) is rare and
      infrequently reported. From a study of 30 patients it appears that EGD often
      occurs with concomitant squamous dysplasia and also benign and preinvasive
      glandular changes in the cervix and endometrium. If EGD is detected on cervical
      biopsy hysteroscopy, dilatation and curettage and cone biopsy should be
      performed.

PMID- 8995569
TI  - Telomerase activity in gynecologic tumors.
AB  - The standard telomeric repeat assay protocol (TRAP) was used to examine
      telomerase activity in 16 ovarian tumors, 16 cervical carcinomas, 4 uterine
      tumors, and 3 vaginal tumors. Telomerase activity was detected in 95% of these
      tumors, 88% of ovarian malignancies, and 100% of cervical, endometrial, and
      vaginal malignancies. In contrast, telomerase activity was not evident in normal
      tissues or in benign proliferative lesions, such as leiomyomas, condyloma
      acuminata, and simple endometrial hyperplasia. These results suggest that
      telomerase activation is associated with immortalization or malignant
      transformation of gynecologic tumors.

PMID- 8995570
TI  - Spontaneous arterial thrombosis with an advanced ovarian malignancy.
AB  - Arterial thromboembolic disease almost always occurs in the setting of
      significant cardiovascular disease. Fewer than 10% of patients have no known
      etiology and only rarely is malignancy implicated. A review of the literature
      revealed only one prior report associated with a gynecologic malignancy, and this
      occurred in the lower extremities in a postoperative setting. We report here the
      case of a woman with arterial occlusion of her left upper extremity who was
      subsequently diagnosed as having ovarian adenocarcinoma. Her dramatic response to
      chemotherapy is described, and the diagnosis and management of arterial occlusion
      is reviewed.

PMID- 8995571
TI  - Neurotropic desmoplastic melanoma of the vulva.

PMID- 8995572
TI  - Correlation between colposcopically directed biopsy and loop excision.

PMID- 8995573
TI  - Malignant rhabdoid tumor of the uterine corpus.

PMID- 8995574
TI  - Endometrial carcinoma--relative effectiveness of adjuvant irradiation vs therapy
      reserved for relapse.

PMID- 8995575
TI  - What is the proper extent of an inguinal lymphadenectomy for early vulvar cancer?

PMID- 8995576
TI  - The randomized clinical trial methodology is the most efficient and effective in
      evaluating new treatment strategies.

PMID- 8995577
TI  - AAEM minimonograph #47: normative data in electrodiagnostic medicine. ff.
AB  - This article reviews, without mathematics, the important principles governing the
      acquisition and use of normative data in electrodiagnostic medicine. Common flaws
      in neurophysiological normative data include vague clinical criteria for
      establishing freedom from disease, samples that are too small and inadequately
      stratified, and application of Gaussian statistics to non-Gaussian variables.
      Other problematic issues concern the trade-off between permissible false
      positivity and false-negativity in defining the limits of normative from sample
      data, test-retest variability, and the use of multiple independent test
      measurements in each electrodiagnostic examination. The following standards for
      normative data are proposed: (1) standardized objective determination of freedom
      from disease; (2) appropriately large sample of normal subjects; (3) proportional
      statification of normal subjects for known relevant variables; (4) test of
      Gaussian fit for application of Gaussian statistics; and (5) data presentation by
      percentiles when Gaussian fit is in doubt. Many existing normative studies in
      clinical neurophysiology do not meet these standards. High-quality normative
      data, readily accessible, is essential for the accurate electrodiagnosis of
      neuromuscular diseases.

PMID- 8995578
TI  - Motor nerve biopsy studies in motor neuropathy and motor neuron disease.
AB  - The clinical presentation of motor neuropathy often resembles that of motor
      neuron disease, sometimes leading to an erroneous diagnosis. Moreover, the
      underlying pathological process in motor neuropathy has been rarely investigated
      and there are no systematic studies of the affected motor nerves. We describe a
      new motor nerve biopsy procedure, performed in 15 patients: 6 with motor
      neuropathy and 9 with motor neuron disease. The motor branch from the anterior
      division of the obturator nerve to the gracilis muscle in the thigh was biopsied.
      In both groups of patients the motor nerves exhibited depletion of myelinated
      nerve fibers. In motor neuropathy there was a significantly higher density of
      regenerative clusters of small myelinated fibers in comparison to motor nerves
      from patients with motor neuron disease. In addition, in 3 patients with motor
      neuropathy there was evidence for demyelination with thinly myelinated axons and
      small onion bulb formations. These pathological studies of motor nerve biopsies
      can help to differentiate motor neuropathy from motor neuron disease.

PMID- 8995579
TI  - Motor unit number estimation: sample size considerations.
AB  - A computer model of the motor unit number estimation procedure was developed to
      evaluate the sampling error associated with estimates of the number of motor
      units in muscles. Two different distributions were used to model the motor unit
      amplitude distribution and were chosen in such a manner that they qualitatively
      matched the distributions observed under both normal and neurogenic conditions.
      As expected, the results indicated that estimation error decreases as a function
      of sample size. However, the relationship between these two variables was
      nonlinear in the sense that successive increases in sample size lead to
      progressively smaller decreases in estimation error. The results also indicated
      that the shape of the motor unit amplitude distribution plays an important role.
      Specifically, estimates obtained using the distribution modeling normal muscle
      were generally higher than the actual number of motor units in the muscle, which
      was not the case for the distribution modeling neurogenic muscle. In addition,
      the neurogenic distribution was associated with much smaller estimation error,
      suggesting that motor unit number estimation is well suited to the analysis of
      neurogenic disease processes.

PMID- 8995580
TI  - Inaccurate projection of rat soleus motoneurons: a comparison of nerve repair
      techniques.
AB  - The objectives of this study were 1) to determine the degree to which soleus
      motoneurons find their appropriate target following crush and transection
      injuries to the sciatic nerve, and 2) to determine whether repair of a transected
      nerve with a silicone tube leads to greater specificity of reinnervation and
      recovery of muscle function than the standard epineurial suture repair method.
      Sixty adult female Sprague-Dawley rats were randomly assigned to one of three
      sciatic nerve injury groups: crush injury, transection with epineurial suture
      repair, or transection with a silicone tube repair. The degree to which soleus
      motoneurons were able to find their appropriate target following a sciatic nerve
      injury was examined using a double labeling dye technique in which the original
      soleus motor pool was labeled with fast blue and reinnervating motoneurons were
      labeled with Dil. Soleus motoneurons were able to find their appropriate target
      following a crush injury. The accuracy of reinnervation following a transection
      injury and repair, however, was relatively poor. Only 14% of the original soleus
      motoneurons found the correct target following a transection injury. Repair of a
      lesioned nerve with a silicone tube and a 5-mm gap as opposed to epineurial
      sutures did not increase the specificity of reinnervation or the degree of muscle
      recovery.

PMID- 8995581
TI  - Physiological tremor analysis of patients with anti-myelin-associated
      glycoprotein associated neuropathy and tremor.
AB  - Tremor is often associated with anti-myelin-associated glycoprotein (anti-MAG)
      peripheral neuropathy (PN), but its physiology has never been accurately
      described. This study quantified the physiological characteristics of tremors in
      patients with anti-MAG demyelinating PN. Eighteen patients with tremor and PN
      with demyelinating features (ages 30-86, mean = 66.5 years) were evaluated for
      anti-MAG antibodies (positive considered > or = 1:3200) and for tremor amplitude,
      frequency, side-to-side relationships, and electromyographic (EMG) activation
      patterns. Thirteen patients had anti-MAG titers >1:3200 and 8 had both positive
      anti-MAG titers and tremors. Anti-MAG PN patients revealed tremors higher in
      amplitude, lower in frequency, with greater side-to-side amplitude ratios,
      greater amplitude variability, and more consistent cocontracting antagonist EMG
      patterns that do not attenuate with inertial loading. We conclude that anti-MAG
      PN tremor is not due only to exaggerated physiologic mechanisms but may reflect a
      distinctive form of neurogenic tremor.

PMID- 8995582
TI  - Progressive motor neuron impairment in an animal model of familial amyotrophic
      lateral sclerosis.
AB  - Mutations of Cu,Zn superoxide dismutase cause an autosomal dominant form of
      familial amyotrophic lateral sclerosis. An animal model of the disease has been
      produced by expressing mutant human SOD1 in transgenic mice (G93A). In order to
      quantify the dysfunction of the motor unit in transgenic mice, electromyographic
      recordings were performed during the course of the disease. The first alterations
      in neuromuscular function appeared between P63 and P90. The deficits became even
      more striking after P100; compound muscle action potentials in the hindlimb
      decreased by 80% of initial value. Spontaneous fibrillation potentials were
      measured in more than 50% of transgenic mice. The number of motor units in the
      gastrocnemius muscle was progressively reduced over time, down to 18% of the
      control value at P130. Moreover, distal motor latencies increased after P120.
      These data suggest that the initial dysfunctions of motor unit are related to a
      severe motor axonal degeneration, which is followed at later periods by myelin
      alteration.

PMID- 8995583
TI  - End-plate electromyography: use of spectral analysis of end-plate noise.
AB  - An automated technique for estimating the channel open time of human end-plate
      acetylcholine receptors (AChR) is described. The method, which is based on the
      power spectral analysis of electromyographic end-plate noise, is simple and
      permits a rapid estimation of the dominant AChR ion channel kinetics. Values of
      AChR channel open time determined by spectral analysis of end-plate noise in
      adults (1.23 +/- 0.01 ms at 33 degrees C) were consistently shorter than those
      estimated from the decay phase of extracellularly recorded miniature end-plate
      potentials. The channel open time extracted from the end-plate noise compared
      well with that derived from the analysis of in vitro recorded acetylcholine
      induced current noise. Therefore, spectral analysis of end-plate noise may
      provide a good estimation of the kinetics of the human AChR ion channel. The
      technique is particularly useful in identifying congenital myasthenic syndromes
      with altered AChR ion channel function.

PMID- 8995584
TI  - Subacute uremic and diabetic polyneuropathy.
AB  - We present 4 patients who had a subacute, predominantly motor polyneuropathy
      associated with diabetes mellitus and end-stage renal disease.
      Electrophysiological studies and muscle biopsy indicated a primary axonal
      degeneration of nerve with secondary segmental demyelination, and mild to
      moderate, acute and chronic denervation of muscle. A relative absence of
      denervation potentials on needle electromyography was an unusual feature. Three
      of our patients improved with a switch from conventional to high-flux
      hemodialysis. We speculate on possible mechanisms.

PMID- 8995585
TI  - Abnormalities of cortical inhibitory neurons in amyotrophic lateral sclerosis.
AB  - We have used peristimulus time histograms to study how paired, transcranial
      magnetic stimulation alters the firing of single motor units and the magnitude of
      unitary excitatory postsynaptic potentials (EPSPs) recorded from the extensor
      digitorum communis muscle. With stimulus intensity at threshold and an
      interstimulus interval of 30 ms, normal subjects (n = 20) demonstrated marked
      inhibition with a mean test/conditioning EPSP ratio of 13.8% (range 0-51%) and in
      7 subjects the ratio was 0 (100% inhibition). In amyotrophic lateral sclerosis
      (ALS) the ratio was 133% (range 64-267%), P < 0.001. Fifty percent of patients
      had a test/conditioning EPSP ratio greater than 100% (0 inhibition). The
      abnormalities were independent of disease severity, bulbar versus spinal ALS,
      more prominent upper versus lower motor neuron findings, and disease duration.
      Normal inhibition occurred in 3 individuals, 1 each with multiple sclerosis,
      Kennedy's syndrome, and monomelic amyotrophy. We speculate that the marked loss
      of inhibition seen in all patients with ALS, which may be unique to this
      disorder, reflects loss of inhibitory modulation of the corticomotoneuron and
      could result in their chronic excitatory drive and eventual demise.

PMID- 8995586
TI  - Spontaneous myopathy in the SJL/J mouse: pathology and strength loss.
AB  - Myopathy has been found to develop spontaneously in 100% of SJL/J mice between 6
      and 8 months of age. Extent of muscular involvement and mouse strength were
      quantified in SJL/J mice and Balb/c control mice 2-16 months old. Muscle from
      young SJL/J mice exhibited histopathological abnormalities and occasional
      inflammatory infiltrate. By 6 months, 78% of SJL/J mice had developed active
      myopathy. By 8 months, all SJL/J mice examined had active disease with a mean of
      12.9% of muscle fibers affected. Replacement of muscle fibers by fat and/or
      collagen began at 10 months and was pronounced by 14 months. Significant
      decreases in strength scores (total body pulling force) at 6 months and 10 months
      of age reflected the onset of active myopathy and the onset of muscle
      degeneration, respectively. The spontaneous onset and 100% incidence of myopathy
      in the SJL/J mouse line should provide a useful model for idiopathic myopathy.

PMID- 8995587
TI  - Evaluation of neuropathy in patients on suramin treatment.
AB  - Suramin, a promising chemotherapeutic agent, causes a dose-limiting sensorimotor
      polyneuropathy. We undertook a phase 1 study of suramin that included serial
      neurologic and electrophysiologic examinations as part of the safety evaluation.
      We found that 6 of 41 (15%) patients developed suramin-induced demyelinating
      neuropathy which resembled Guillain-Barre syndrome clinically. There was 1
      asymptomatic patient with electrophysiologic abnormalities suggestive of a
      demyelinating neuropathy. In addition, 1 patient with mild axonal neuropathy at
      baseline had deterioration of his symptoms during suramin treatment. Four
      asymptomatic patients developed electrophysiologic findings suggestive of a mild
      axonal neuropathy. We conclude that: (1) serial electrophysiologic monitoring is
      helpful for early detection of suramin-induced neuropathy; and (2) fixed dosing
      schedule of suramin without adaptive control does not lead to an increased
      incidence of demyelinating neuropathy when compared to adaptively controlled
      dosing schedules.

PMID- 8995588
TI  - Expression of CD59, a regulator of the membrane attack complex of complement, on
      human skeletal muscle fibers.
AB  - Control of complement deposition on autologous cells is mediated by a group of
      complement regulatory membrane proteins acting at different levels of the
      complement cascade. Decay accelerating factor (CD55) prevents the assembly of C3
      convertases and CD59 membrane inhibitor of reactive lysis (MIRL) restricts
      homologous complement lysis by the membrane attack complex of complement (MAC) by
      inhibition of C5b-8 catalyzed insertion of C9. The aim of this work was to study
      the eventual expression of CD55 and CD59 on human skeletal muscle fibers. Highly
      sensitive immunoblotting using murine monoclonal antibodies showed that CD59, but
      not CD55, was present in skeletal muscle fibers. Immunocytochemistry with a
      monoclonal antibody against CD59 demonstrated a dense granular immunostaining
      mainly localized at the level of the sarcolemma. Thus, CD59, but not CD55, is
      expressed on normal skeletal muscle fibers. CD59 may play a prominent role in
      preventing MAC deposition and subsequent complement-mediated damage in myopathies
      where the complement system activation is involved.

PMID- 8995589
TI  - Dejerine-Sottas neuropathy in mother and son with same point mutation of PMP22
      gene.
AB  - We studied a 25-year-old black woman with healthy parents and her 2-year, 11
      month-old son. Her motor development was delayed and she started to walk with
      support when she was 6 years old. She never walked independently and had always
      used a wheelchair. Neurological evaluation showed severe weakness and atrophy of
      her feet, legs, and hands, bilateral pes cavus and hammertoes, corrected
      scoliosis, hypesthesia for proprioception and vibration sense in both feet and
      ankles, and areflexia. She had normal intelligence. Her son also had delayed
      motor milestones and was still unable to stand and walk independently at almost 3
      years. Neurological evaluation revealed diffuse muscle hypotonia and weakness
      with generalized areflexia and normal intelligence. No muscle atrophies or feet
      deformities were noticed. Nerve conduction velocities showed significant slowing
      (less than 5 m/s) with prolonged distal latencies (above 30 ms). Compound motor
      action potential amplitudes were markedly reduced. Electromyography revealed
      polyphasic motor unit potentials. Molecular genetic studies indicated a Trembler
      type missense point mutation of exon 4 of the peripheral myelin protein 22 gene
      that led to the substitution of a spartic acid for glycine in both the mother and
      her son. Her parents showed normal DNA studies.

PMID- 8995590
TI  - Adult botulism.

PMID- 8995591
TI  - Pancreatic adenocarcinoma presenting as a monomelic motor neuronopathy.

PMID- 8995592
TI  - Zidovudine and human immunodeficiency virus-associated peripheral neuropathies:
      low intake in patients with mononeuropathy multiplex and no evidence for
      neurotoxicity.

PMID- 8995593
TI  - The effects of shounousui on the three responses of the blink reflex in man.

PMID- 8995594
TI  - An electrophysiological demonstration of polysegmental innervation in the lumbar
      medial paraspinal muscles.

PMID- 8995595
TI  - The assessment of diabetic polyneuropathy in daily clinical practice:
      reproducibility and validity of Semmes Weinstein monofilaments examination and
      clinical neurological examination.

PMID- 8995596
TI  - What is the future for intramuscular administration of basic fibroblast growth
      factor in muscular diseases?

PMID- 8995597
TI  - Lumbrical-interossei studies in distal ulnar neuropathy.

PMID- 8995598
TI  - A new source of electromyographic artifact: mobile phones.

PMID- 8995599
TI  - Cerebral lymphoma in a patient with immunoglobulin paraproteinemic
      polyneuropathy.

PMID- 8995600
TI  - HSP72 expression in malignant hyperthermia and normal muscle following exposure
      to caffeine and halothane.

PMID- 8995601
TI  - On viruses, sex, and motherhood.

PMID- 8995602
TI  - Expression of gamma interferon by simian immunodeficiency virus increases
      attenuation and reduces postchallenge virus load in vaccinated rhesus macaques.
AB  - Simian immunodeficiency virus (SIV) infection of macaques is a model for human
      immunodeficiency virus (HIV) infection. We have previously reported the
      construction and characterization of an SIV vector with a deletion in the nef
      gene (SIV(delta nef)) and expressing gamma interferon (SIV(HyIFN)) (L. Giavedoni
      and T. Yilma, J. Virol. 70:2247-2251, 1996). We now show that rhesus macaques
      vaccinated with SIV(HyIFN) have a lower viral load than a group similarly
      immunized with SIV(delta nef). Viral loads remained low in the SIV(HyIFN)
      vaccinated group even though SIV expressing gamma interferon could not be
      isolated after 6 weeks postimmunization in these animals. All immunized and two
      naive control macaques became infected when challenged with virulent SIV(mac251),
      at 25 weeks postvaccination. In contrast to the two naive controls that died by
      12 and 18 weeks postchallenge, all vaccinated animals remained healthy for more
      than 32 weeks. In addition, postchallenge cell-associated virus load was
      significantly lower in SIV(HyIFN)-immunized animals than in the group vaccinated
      with SIV(delta nef). These findings indicate that cytokine-expressing viruses can
      provide a novel approach for development of safe and efficacious live attenuated
      vaccines for AIDS.

PMID- 8995604
TI  - Infectious properties of human immunodeficiency virus type 1 mutants with
      distinct affinities for the CD4 receptor.
AB  - Recent evidence suggests that primary patient isolates of T-cell-tropic human
      immunodeficiency virus type 1 (HIV-1 ) have lower affinities for CD4 than their
      laboratory-adapted derivatives, that this may partly result from tighter gp120
      gp41 bonds that constrain the CD4 binding sites of the primary viruses, and that
      selection for increased CD4 affinity may be the principal factor in laboratory
      adaptation of HIV-1 (S. L. Kozak, E. J. Platt, N. Madani, F. E. Ferro, Jr., K.
      Peden, and D. Kabat, J. Virol. 71:873-882, 1997). These conclusions were based on
      studies with a panel of HeLa-CD4 cell clones that differ in CD4 levels over a
      broad range, with laboratory-adapted viruses infecting all clones with equal
      efficiencies and primary T-cell-tropic viruses infecting the clones in proportion
      to cellular CD4 levels. Additionally, all of the primary and laboratory-adapted T
      cell-tropic viruses efficiently used CXCR-4 (fusin) as a coreceptor. To test
      these conclusions by an independent approach, we studied mutations in the
      laboratory-adapted virus LAV/IIIB that alter the CD)4 binding region of gp120 and
      specifically reduce CD4 affinities of free gp 120 by 85 to 98% (U. Olshevsky et
      al., J. Virol. 64:5701-5707, 1990). These mutations reduced virus titers to
      widely varying extents that ranged from severalfold to several orders of
      magnitude and converted infectivities on the HeLa-CD4 panel from CD4 independency
      to a high degree of CD4 dependency that resembled the behavior of primary patient
      viruses. The relative infectivities of the mutants correlated closely with their
      sensitivities to inactivation by soluble CD4 but did not correlate with the
      relative CD4 affinities of their free gp120s. Most of the mutations did not
      substantially alter envelope glycoprotein synthesis, processing, expression on
      cell surfaces, incorporation into virions, or rates of gp120 shedding from
      virions. However, one mutation (D457R) caused a decrease in gp160 processing by
      approximately 80%. The fact that several mutations increased rates of spontaneous
      viral inactivation (especially D368P) suggests that HIV-1 life spans may be
      determined by structural stabilities of viral envelope glycoproteins. All of the
      wild-type and mutant viruses were only slowly and inefficiently adsorbed onto
      cultured CD4-positive cells at 37 degrees C, and the gradual declines in viral
      titers in the media were caused almost exclusively by spontaneous inactivation
      rather than by adsorption. The extreme inefficiency with which infectious HIV-1
      is able to infect cultured susceptible CD4-positive cells in standard assay
      conditions casts doubt on previous inferences that the vast majority of
      retrovirions produced in cultures are noninfectious. Apparent infectivity of T
      cell-tropic HIV-1 in culture is limited by productive associations with CD4 and
      is influenced in an interdependent manner by CD4 affinities of viral gp120-gp41
      complexes and quantities of cell surface CD4.

PMID- 8995603
TI  - CD4, CXCR-4, and CCR-5 dependencies for infections by primary patient and
      laboratory-adapted isolates of human immunodeficiency virus type 1.
AB  - We have used a focal infectivity method to quantitatively analyze the CD4, CXCR
      4, and CCR-5 dependencies for infections by diverse primary patient (PR) and
      laboratory-adapted (LA) isolates of human immunodeficiency virus type 1 (HIV-1).
      Infectivities of T-cell-tropic viruses were analyzed in a panel of HeLa-CD4 cell
      clones that have distinct quantities of CD4 and in human astroglioma U87MG-CD4
      cells that express a large quantity of CD4 and become highly susceptible to
      infection after transfection with a CXCR-4 expression vector. The latter analysis
      indicated that PR as well as LA T-cell-tropic viruses efficiently employ CXCR-4
      as a coreceptor in an optimal human cell line that contains abundant CD4.
      Previous uncertainties regarding coreceptor usage by PR T-cell-tropic HIV-1
      isolates may therefore have derived from the assay conditions. As reported
      previously, unrelated LA and PR T-cell-tropic HIV-1 isolates differ in
      infectivities for the HeLa-CD4 clonal panel, with LA viruses infecting all clones
      equally and PR viruses infecting the clones in proportion to cellular CD4
      quantities (D. Kabat, S. L. Kozak, K. Wherly, and B. Chesebro, J. Virol. 68:2570
      2577, 1994). To analyze the basis for this difference, we used the HeLa-CD4 panel
      to compare a molecularly cloned T-cell-tropic PR virus (ELI1) with six of its
      variants that grow to different extents in CD4-positive leukemic cell lines and
      that differ only at specific positions in their gp120 and gp41 envelope
      glycoproteins. All mutations in gp120 or gp41 that contributed to laboratory
      adaptation preferentially enhanced infectivity for cells that had little CD4 and
      thereby decreased the CD4 dependencies of the infections. There was a close
      correlation between abilities of T-cell-tropic ELI viruses to grow in an expanded
      repertoire of leukemic cell lines, the reduced CD4 dependencies of their
      infections of the HeLa-CD4 panel, and their sensitivities to inactivation by
      soluble CD4 (sCD4). Since all of the ELI viruses can efficiently use CXCR-4 as a
      coreceptor, we conclude that an increase in viral affinity for CD4 rather than a
      switch in coreceptor specificity is principally responsible for laboratory
      adaption of T-cell-tropic HIV-1. Syncytium-inducing activities of the ELI
      viruses, especially when analyzed on cells with low amounts of CD4, were also
      highly correlated with their laboratory-adapted properties. Results with
      macrophage-tropic HIV-1 were strikingly different in both coreceptor and CD4
      dependencies. When assayed in HeLa-CD4 cells transfected with an expression
      vector for CCR-5, macrophage-tropic HIV-1 isolates that had been molecularly
      cloned shortly after removal from patients were equally infectious for cells that
      had low or high CD4 quantities. Moreover, despite their substantial infectivities
      for cells that had only a trace of CD4, macrophage-tropic isolates were
      relatively resistant to inactivation by sCD4. We conclude that T-cell-tropic PR
      viruses bind weakly to CD4 and preferentially infect cells that coexpress CXCR-4
      and large amounts of CD4. Their laboratory adaptation involves corresponding
      increases in affinities for CD4 and in abilities to infect cells that have
      relatively little CD4. In contrast, macrophage-tropic HIV-1 appears to interact
      weakly with CD4 although it can infect cells that coexpress CCR-5 and small
      quantities of CD4. We propose that cooperative binding of macrophage-tropic HIV-1
      onto CCR-5 and CD4 may enhance virus adsorption and infectivity for cells that
      have only a trace of CD4.

PMID- 8995605
TI  - Mapping and characterization of the interaction domains of human papillomavirus
      type 16 E1 and E2 proteins.
AB  - The papillomavirus E1 and E2 proteins are both necessary and sufficient in vivo
      for efficient origin-dependent viral DNA replication. The ability of E1 and E2 to
      complex with each other appears to be essential for efficient viral DNA
      replication. In this study, we used the yeast two-hybrid system and in vitro
      binding assays to map the domains of the human papillomavirus type 16 (HPV16) E1
      and E2 proteins required for complex formation. The amino-terminal 190-amino-acid
      domain of HPV16 E2 was both required and sufficient for E1 binding. The carboxyl
      terminal 229 amino acids of E 1 were essential for binding E2, and the amino
      terminal 143 amino acids of HPV16 E1 were dispensable. Although the ability of
      the E1 minimal domain (amino acids [aa] 421 to 649) to interact with E2 was
      strong at 4 degrees C, it was significantly reduced at temperatures above 25
      degrees C. A larger domain of E1 from aa 144 to 649 bound E2 efficiently at any
      temperature, suggesting that aa 144 to 420 of E1 may play a role in the HPV16 E1
      E2 interaction at physiological temperatures.

PMID- 8995606
TI  - Characterization of a second cleavage site and demonstration of activity in trans
      by the papain-like proteinase of the murine coronavirus mouse hepatitis virus
      strain A59.
AB  - The 21.7-kb replicase locus of mouse hepatitis virus strain A59 (MHV-A59) encodes
      several putative functional domains, including three proteinase domains. Encoded
      closest to the 5' terminus of this locus is the first papain-like proteinase (PLP
      1) (S. C. Baker et al., J. Virol. 67:6056-6063, 1993; H.-J. Lee et al., Virology
      180:567-582, 1991). This cysteine proteinase is responsible for the in vitro
      cleavage of p28, a polypeptide that is also present in MHV-A59-infected cells.
      Cleavage at a second site was recently reported for this proteinase (P. J.
      Bonilla et al., Virology 209:489-497, 1995). This new cleavage site maps to the
      same region as the predicted site of the C terminus of p65, a viral polypeptide
      detected in infected cells. In this study, microsequencing analysis of the
      radiolabeled downstream cleavage product and deletion mutagenesis analysis were
      used to identify the scissile bond of the second cleavage site to between Ala832
      and Gly833. The effects of mutations between the P5 and P2' positions on the
      processing at the second cleavage site were analyzed. Most substitutions at the
      P4, P3, P2, and P2' positions were permissive for cleavage. With the exceptions
      of a conservative P1 mutation, Ala832Gly, and a conservative P5 mutation,
      Arg828Lys, substitutions at the P5, P1, and P1' positions severely diminished
      second-site proteolysis. Mutants in which the p28 cleavage site (Gly247 / Val248)
      was replaced by the Ala832 / Gly833 cleavage site and vice versa were found to
      retain processing activity. Contrary to previous reports, we determined that the
      PLP-1 has the ability to process in trans at either the p28 site or both cleavage
      sites, depending on the choice of substrate. The results from this study suggest
      a greater role by the PLP-1 in the processing of the replicase locus in vivo.

PMID- 8995607
TI  - RNA-targeted activators, but not DNA-targeted activators, repress the synthesis
      of short transcripts at the human immunodeficiency virus type 1 long terminal
      repeat.
AB  - The human immunodeficiency virus type 1 (HIV-1) promoter directs the synthesis of
      two types of RNA molecules: full-length transcripts, whose synthesis is activated
      by the viral activator Tat, and short transcripts, whose synthesis is dependent
      on the inducer of short transcripts (IST), a bipartite DNA element located in
      large part downstream of the HIV-1 transcriptional start site. In the absence of
      Tat, short transcripts constitute the large majority of the RNA molecules
      synthesized from the HIV-1 promoter. In the presence of Tat, synthesis of the
      short transcripts is repressed and synthesis of the full-length transcripts is
      activated. Tat is unique among transcriptional activators in acting through an
      RNA target, the TAR element. However, Tat has been shown to activate
      transcription from a DNA target when fused to the appropriate DNA binding domain,
      raising the question of why Tat has been directed to the RNA. Here we have
      compared the abilities of Tat and other RNA- and DNA-bound activators to
      stimulate transcription from the HIV-1 promoter. We show that DNA-targeted
      activators, including DNA-targeted Tat, activate the synthesis of both short and
      long transcripts, while RNA-targeted Tat and another RNA-targeted activator
      activate the synthesis of full-length transcripts but specifically repress that
      of short transcripts. The unique ability of RNA-targeted activators to down
      regulate short transcript synthesis suggests that Tat is directed to the RNA
      specifically for the purpose of repressing short transcripts.

PMID- 8995608
TI  - An amino-terminal domain of the Sendai virus nucleocapsid protein is required for
      template function in viral RNA synthesis.
AB  - The nucleocapsid protein (NP) of Sendai virus encapsidates the genome RNA,
      forming a helical nucleocapsid which is the template for RNA synthesis by the
      viral RNA polymerase. The NP protein is thought to have both structural and
      functional roles, since it is an essential component of the NP0-P (P,
      phosphoprotein), NP-NP, nucleocapsid-polymerase, and RNA-NP complexes required
      during viral RNA replication. To identify domains in the NP protein, mutants were
      constructed by using clustered charge-to-alanine mutagenesis in a highly charged
      region from amino acids 107 to 129. Each of the mutants supported RNA
      encapsidation in vitro. The product nucleocapsids formed with three mutants,
      NP114, NP121, and NP126, however, did not serve as templates for further
      amplification in vivo, while NP107, NP108, and NP111 were nearly like wild-type
      NP in vivo. This template defect in the NP mutants from amino acids 114 to 129
      was not due to a lack of NP0-P, NP-NP, or nucleocapsid-polymerase complex
      formation, since these interactions were normal in these mutants. We propose that
      amino acids 114 to 129 of the NP protein are required for the nucleocapsid to
      function as a template in viral genome replication.

PMID- 8995609
TI  - A novel antibody-dependent cellular cytotoxicity epitope in gp120 is identified
      by two monoclonal antibodies isolated from a long-term survivor of human
      immunodeficiency virus type 1 infection.
AB  - Two monoclonal antibodies (MAbs), 42F and 43F, were isolated some 14 months apart
      from a single long-term survivor of human immunodeficiency virus type 1 (HIV-1)
      infection. These MAbs were found to be indistinguishable in terms of their
      isotypes, specificities, affinities, and biological activities. Both 42F and 43F
      directed substantial antibody-dependent cellular cytotoxicity (ADCC) against
      cells infected with four divergent lab-adapted strains of HIV-1, but no
      neutralizing activity against these strains was detectable. The ability of MAbs
      42F and 43F, as well as that of MAbs against two other gp120 epitopes, to direct
      ADCC against uninfected CD4+ cells to which recombinant gp120SF2 had been
      adsorbed (i.e., "innocent bystanders") was demonstrated to be less efficient by
      at least an order of magnitude than their ability to direct ADCC against HIV-1
      infected cells. Flow cytometry analyses showed that 42F and 43F also bind to
      native primary isolate Envs from clades B and E expressed on cell surfaces. By
      direct binding and competition assays, it was demonstrated that the 42F/43F
      epitope lies in a domain of gp120 outside the previously described CD4-binding
      site and V3 loop ADCC epitope clusters. Immunoblot analysis revealed that the
      42F/43F epitope is not dependent on disulfide bonds or N-linked glycans in gp120.
      Epitope mapping of 42F and 43F by binding to linear peptides demonstrated
      specificity of these MAbs for a sequence of 10 amino acids in the C5 domain
      comprising residues 491 to 500 (Los Alamos National Laboratory numbering for the
      HXB2 strain). Thus, 42F and 43F define a new ADCC epitope in gp120. Because of
      the relative conservation of this epitope and the fact that it appears to have
      been significantly immunogenic in the individual from which these MAbs were
      derived, it may prove to be a useful component of HIV vaccines. Furthermore,
      these MAbs may be used as tools to probe the potential importance of ADCC as an
      antiviral activity in HIV-1 infection.

PMID- 8995610
TI  - Genetic exchange by recombination or reassortment is infrequent in natural
      populations of a tripartite RNA plant virus.
AB  - Two hundred seventeen field isolates of cucumber mosaic cucumovirus (CMV),
      sampled from 11 natural populations, were typed by RNase protection assay (RPA)
      using probes from the genomic RNAs of strains in subgroup I and in subgroup II of
      CMV strains. Most (85%) of the analyzed isolates belonged to subgroup I. For
      these subgroup I isolates, only two clearly different RPA patterns, A and B, were
      found for each of four probes representing RNA1, RNA2, and each of the two open
      reading frames in RNA3. On the basis of these RPA patterns for each probe,
      different haplotypes were defined. The frequency composition for these haplotypes
      differed for the various analyzed populations, with no correlation with place or
      year of sampling. This genetic structure corresponds to a metapopulation with
      local extinctions and recolonizations. Most subgroup I isolates (73%) belonged to
      haplotypes with RPA pattern A (type 1) or B (type 2) for all four probes. A
      significant fraction of subgroup I isolates (16%) gave evidence of mixed
      infections with these two main types, from which genetic exchange could occur.
      Genetic exchange by segment reassortment was seen to occur: the fraction of
      reassortant isolates was 4%, reassortment did not occur at random, and
      reassortants did not become established in the population. Thus, there is
      evidence of selection against reassortment between types 1 and 2 of subgroup I
      isolates. Aphid transmission experiments with plants doubly infected with type 1
      and type 2 isolates gave further evidence that reassortment is selected against
      in CMV. Genetic exchange by recombination was detected for RNA3, for which two
      RPA probes were used. Recombinant isolates amounted to 7% and also did not become
      established in CMV populations. Sequence analyses of regions of RNA1, RNA2, and
      RNA3 showed that there are strong constraints to maintain the encoded sequence
      and also gave evidence that these constraints may have been different during
      divergence of types 1 and 2 and, later on, during diversification of these two
      types. Constraints to the evolution of encoded proteins may be related to
      selection against genetic exchange. Our data, thus, do not favor current
      hypotheses that explain the evolution of multipartite viral genomes to promote
      genetic exchange.

PMID- 8995612
TI  - Characterization of two temperature-sensitive mutants of coronavirus mouse
      hepatitis virus strain A59 with maturation defects in the spike protein.
AB  - Two temperature-sensitive (ts) mutants of mouse hepatitis virus strain A59, ts43
      and ts379, have been described previously to be ts in infectivity but unaffected
      in RNA synthesis (M. J. M. Koolen, A. D. M. E. Osterhaus, G. van Steenis, M. C.
      Horzinek, and B. A. M. van der Zeijst, Virology 125:393-402, 1983). We present a
      detailed analysis of the protein synthesis of the mutant viruses at the
      permissive (31 degrees C) and nonpermissive (39.5 degrees C) temperatures. It was
      found that synthesis of the nucleocapsid protein N and the membrane protein M of
      both viruses was insensitive to temperature. However, the surface protein S of
      both viruses was retained in the endoplasmic reticulum at the nonpermissive
      temperature. This was shown first by analysis of endoglycosidase H-treated and
      immunoprecipitated labeled S proteins. The mature Golgi form of S was not present
      at the nonpermissive temperature for the ts viruses, in contrast to wild-type
      (wt) virus. Second, gradient purification of immunoprecipitated S after pulse
      chase labeling showed that only wt virus S was oligomerized. We conclude that the
      lack of oligomerization causes the retention of the ts S proteins in the
      endoplasmic reticulum. As a result, ts virus particles that were devoid of S were
      produced at the nonpermissive temperature. This result could be confirmed by
      biochemical analysis of purified virus particles and by electron microscopy.

PMID- 8995611
TI  - A novel 165-base-pair terminal repeat sequence is the sole cis requirement for
      the adeno-associated virus life cycle.
AB  - Adeno-associated virus (AAV) replication is dependent on two copies of a 145-bp
      inverted terminal repeat (ITR) that flank the AAV genome. This is the primary cis
      acting element required for productive infection and the generation of
      recombinant AAV (rAAV) vectors. We have engineered a plasmid (pDD-2) containing
      only 165 bp of AAV sequence: two copies of the D element, a unique sequence
      adjacent to the AAV nicking site, flanking a single ITR. When assayed in vivo,
      this modified hairpin was sufficient for the replication of the plasmid vector
      when Rep and adenovirus (Ad) helper functions were supplied in trans. pDD-2
      replication intermediates were characteristic of the AAV replication scheme in
      which linear monomer, dimer, and other higher-molecular-weight replicative
      intermediates are generated. Compared to infectious AAV clones for replication,
      the modified hairpin vector replicated more efficiently independent of size.
      Further analysis demonstrated conversion of the input circular plasmid to a
      linear substrate with AAV terminal repeat elements at either end as an initial
      step for replication. This conversion was independent of both Rep and Ad helper
      genes, suggesting the role of host factors in the production of these molecules.
      The generation of these substrates suggested resolution of the modified terminal
      repeat through a Holliday-like structure rather than replication as a mechanism
      for rescue. Production of replicative intermediates via this plasmid substrate
      were competent not only for AAV DNA replication but also for encapsidation,
      infection, integration, and subsequent rescue from the chromosome when
      superinfected with Ad and wild-type AAV. These studies demonstrate that this
      novel 165-bp ITR substrate is sufficient in cis for the AAV life cycle and should
      provide a valuable reagent for further dissecting the cis sequences involved in
      AAV replication, packaging, and integration. In addition, this novel plasmid
      vector can be used as a substrate for both rAAV vector production and synthetic
      plasmid vector delivery.

PMID- 8995613
TI  - Independently cloned halves of cytomegalovirus assemblin, An and Ac, can restore
      proteolytic activity to assemblin mutants by intermolecular complementation.
AB  - Herpesviruses encode an essential serine proteinase called assemblin that is
      responsible for cleaving the precursor assembly protein during the process of
      capsid formation. In cytomegalovirus (CMV), assemblin undergoes autoproteolysis
      at an internal (I) site located near the middle of the molecule. I-site cleavage
      converts the enzyme to an active two-chain form consisting of the subunits An and
      Ac. We have recently shown that the recombinant An and Ac subunits can
      spontaneously associate within eukaryotic cells to yield active two-chain
      proteinase. This finding indicates that the subunits are able to independently
      assume their correct functional conformations and led us to test whether they are
      capable of intermolecular complementation. This was done by coexpressing inactive
      mutant (point, deletion, and insertion) forms of assemblin together with the wild
      type subunit (either An or Ac) corresponding to the domain of assemblin that was
      mutated. Results of these experiments showed that both An and Ac are able to
      rescue the enzymatic activity of assemblin mutants. I-site cleavage of the
      mutated assemblin occurred during complementation but was not absolutely
      required, as shown by effective complementation of inactive assemblins with
      noncleavable I sites. We have also shown that intermolecular complementation can
      rescue the activity of an inactive mutant full-length proteinase precursor and
      can occur between different species of CMV (e.g., human CMV subunit can rescue
      activity of mutant simian CMV assemblin). These results indicate that assemblin
      is able to form active multimeric structures that may be of functional
      importance.

PMID- 8995614
TI  - Identification of a cis-acting element in the class I major histocompatibility
      complex gene promoter responsive to activation by retroviral sequences.
AB  - The infection of cells with Moloney murine leukemia virus (M-MuLV) causes an
      increase in specific cellular gene products, including the major
      histocompatibility complex (MHC) class I antigens. This upregulation occurs
      through a transactivation process mediated by the long terminal repeat (LTR) of M
      MuLV, and we show here that the gene activation response to the LTR requires at
      least one specific cis element within the MHC proximal promoter region. Nested
      deletions of MHC class I H-2Kb gene promoter sequence were subcloned into a
      chloramphenicol acetyltransferase (CAT) reporter vector and then transiently
      introduced into BALB/c-3T3 cells expressing M-MuLV or cotransfected into BALB/c
      3T3 cells with a vector containing subgenomic portions of the virus, including
      the LTR. CAT activity assays demonstrated that a minimal H-2Kb gene promoter (-64
      to +12) contained elements sufficient for this transactivation. DNase I
      footprinting assays located a protein-binding site in the region of -64 to -34 bp
      from the transcriptional start site, and point mutation analysis confirmed the
      location of this cis-acting element, designated the let response element (LRE),
      and defined a binding motif. This LRE is distinct from binding sites for
      currently known transcription factors in the class I MHC gene promoter and is
      conserved in the promoters of human and murine MHC class I genes. Mutation of the
      LRE resulted in dramatic reduction in both DNA-protein binding activity in
      electrophoretic mobility shift assay and in the ability of the mutated promoter
      to respond to retroviral transactivation. Addition of the LRE to a heterologous
      promoter conferred the ability to respond to retroviral transactivation.

PMID- 8995616
TI  - Translational regulation of the human cytomegalovirus pp28 (UL99) late gene.
AB  - The pp28 (UL99) gene of human cytomegalovirus is expressed as a true late gene,
      in that DNA synthesis is absolutely required for mRNA expression. Our previous
      studies demonstrated that pp28 promoter sequences from position -40 to +106 are
      sufficient for late gene expression in the context of the viral genome (C. P.
      Kohler, J. A. Kerry, M. Carter, V. P. Muzithras, T. R. Jones, and R. M. Stenberg,
      J. Virol. 68:6589-6597, 1994). To extend these studies, we have examined the
      sequences in the downstream leader region of the pp28 gene for their role in late
      gene expression. Deletion of sequences from position -6 to +46 (deltaSS) results
      in a threefold increase in gene expression in transient assays. In contrast,
      deletion of sequences from position +46 to +88 (deltaA) has little effect on gene
      expression. These results indicate that the sequences from position -6 to +46 may
      repress gene expression. To further analyze this region, site-directed
      mutagenesis was performed. Mutation of residues from either position +1 to +6
      (SS1) or position +12 to +17 (SS2) duplicated the effect of the deltaSS deletion
      mutant, indicating that sequences from position +1 to +17 were important for the
      inhibitory effect. To assess the biological significance of these events, a
      recombinant virus construct containing the deltaSS mutant promoter regulating
      expression of the chloramphenicol acetyltransferase (CAT) reporter gene was
      generated. Analysis of this virus (RV delta SSCAT) revealed that deletion of
      sequences from position -6 to +46 does not alter the kinetic class of this
      promoter. However, the ratio of CAT protein to CAT mRNA levels in RV delta SSCAT
      infected cells was 8- to 12-fold higher than that observed in the parental
      RV24/26CAT-infected cells. These results imply that the leader sequences within
      the pp28 gene can regulate the translation of this late gene.

PMID- 8995615
TI  - Specific initiation of replication at the right-end telomere of the closed
      species of minute virus of mice replicative-form DNA.
AB  - We have developed an in vitro system that supports the replication of natural DNA
      templates of the autonomous parvovirus minute virus of mice (MVM). MVM virion
      DNA, a single-stranded molecule bracketed by short, terminal, self-complementary
      sequences, is converted into double-stranded replicative-form (RF) DNA when
      incubated in mouse A9 fibroblast extract. The 3' end of the newly synthesized
      complementary strand is ligated to the right-end hairpin of the virion strand,
      resulting in the formation of a covalently closed RF (cRF) molecule as the major
      conversion product. cRF DNA is not further replicated in A9 cell extract alone.
      On addition of purified MVM nonstructural protein NS1 expressed from recombinant
      baculoviruses or vaccinia viruses, cRF DNA is processed into a right-end (5' end
      of the virion strand) extended form (5'eRF). This is indicative of NS1-dependent
      nicking of the right-end hairpin at a distinct position, followed by unfolding of
      the hairpin and copying of the terminal sequence. In contrast, no resolution of
      the left-end hairpin can be detected in the presence of NS1. In the course of the
      right-end nicking reaction, NS1 gets covalently attached to the right-end
      telomere of the DNA product, as shown by immunoprecipitation with NS1-specific
      antibodies. The 5'eRF product is the target for additional rounds of NS1-induced
      nicking and displacement synthesis at the right end, arguing against the
      requirement of the hairpin structure for recognition of the DNA substrate by NS1.
      Further processing of the 5'eRF template in vitro leads to the formation of
      dimeric RF (dRF) DNA in a left-to-left-end configuration, presumably as a result
      of copying of the whole molecule by displacement synthesis initiated at the right
      end telomere. Formation of dRF DNA is highly stimulated by NS1. The experimental
      results presented in this report support various assumptions of current models of
      parvovirus DNA replication and provide new insights into the replication
      functions of the NS1 protein.

PMID- 8995617
TI  - Protease-deficient herpes simplex virus protects mice from lethal herpesvirus
      infection.
AB  - Null mutants and attenuated mutants of herpes simplex virus (HSV) have been shown
      to induce immunity against challenge from wild-type virus. Null viruses with a
      defect in late gene products would be expected to express more viral genes than
      viruses with defects in essential early gene products and thus induce a better
      immune response. Herpesviruses encode a late gene product (serine protease) that
      is autocatalytic and cleaves the capsid assembly protein during viral
      replication. To determine whether a virus with a mutation in this gene could
      induce immunity, we constructed a recombinant virus containing the gusA reporter
      gene in the protease domain of the HSV type 1 UL26 open reading frame (ORF).
      Consistent with previous results (M. Gao, L. Matusick-Kumar, W. Hurlburt, S. F.
      DiTusa, W. W. Newcomb, J. C. Brown, P. J. McCann, I. Deckman, and R. J. Colonno,
      J. Virol. 68:3702-3712, 1994), recombinant virus could be isolated only from
      helper cell lines expressing the product of the UL26 ORF. Mice inoculated with
      the recombinant virus were unaffected by doses of virus that were lethal to mice
      infected with wild-type virus. Mice which were previously inoculated with the
      recombinant virus were also protected by a subsequent challenge with wild-type
      virus in a dose-dependent manner. These results indicate that recombinant viruses
      lacking the protease gene are avirulent but render protection from subsequent
      challenge.

PMID- 8995618
TI  - The internal open reading frame within the nucleocapsid gene of mouse hepatitis
      virus encodes a structural protein that is not essential for viral replication.
AB  - The coronavirus mouse hepatitis virus (MHV) contains a large open reading frame
      embedded entirely within the 5' half of its nucleocapsid (N) gene. This internal
      gene (designated I) is in the +1 reading frame with respect to the N gene, and it
      encodes a mostly hydrophobic 23-kDa polypeptide. We have found that this protein
      is expressed in MHV-infected cells and that it is a previously unrecognized
      structural protein of the virion. To analyze the potential biological importance
      of the I gene, we disrupted its expression by site-directed mutagenesis using
      targeted RNA recombination. The start codon for I was replaced by a threonine
      codon, and a stop codon was introduced at a short interval downstream. Both
      alterations created silent changes in the N reading frame. In vitro translation
      studies showed that these mutations completely abolished synthesis of I protein,
      and immunological analysis of infected cell lysates confirmed this conclusion.
      The MHV I mutant was viable and grew to high titer. However, the I mutant had a
      reduced plaque size in comparison with its isogenic wild-type counterpart,
      suggesting that expression of I confers some minor growth advantage to the virus.
      The engineered mutations were stable during the course of experimental infection
      in mice, and the I mutant showed no significant differences from wild type in its
      ability to replicate in the brains or livers of infected animals. These results
      demonstrate that I protein is not essential for the replication of MHV either in
      tissue culture or in its natural host.

PMID- 8995619
TI  - The ICP22 protein of equine herpesvirus 1 cooperates with the IE protein to
      regulate viral gene expression.
AB  - The equine herpesvirus 1 (EHV-1) immediate-early (IE) phosphoprotein is essential
      for the activation of transcription from viral early and late promoters and
      regulates transcription from its own promoter. The EHV-1 EICP22 protein, a
      homolog of ICP22 of herpes simplex virus, increased the in vitro DNA binding
      activity of the IE protein for sequences in the IE, early, and late promoters.
      The EICP22 protein affected the rate as well as the extent of the IE protein
      binding to promoter DNA sequences. To study the DNA binding activity of the IE
      protein, Trp493, Gln495, Asn496, and Lys498 of the WLQN region, which is directly
      involved in DNA binding, were replaced with Ser (IEW493S), Glu (IEQ495E), Ile
      (IEN496I), and Glu (IEK498E), respectively. Gel shift assays revealed that the
      glutathione S-transferase (GST)-IEQ495E(407-615) and GST-IEK498E(407-615)
      proteins failed to bind to the IE promoter, indicating that the Gln and Lys
      residues are important for the DNA binding activity. In the presence of the GST
      EICP22 protein, DNA binding activity of the GST-IEQ495E(407-615) protein was
      restored, suggesting that the EICP22 protein cooperates with the IE protein to
      regulate EHV-1 gene expression. Transient-transfection assays also showed that
      the EICP22 protein allowed the IEQ495E mutant to be functional as a
      transactivator. These results are unique and may represent an important role for
      the EICP22 protein in EHV-1 gene regulation.

PMID- 8995620
TI  - Nef association with human immunodeficiency virus type 1 virions and cleavage by
      the viral protease.
AB  - Nef is a regulatory gene product of human immunodeficiency virus type 1 (HIV-1)
      and other primate lentiviruses which enhances virion infectivity by an unknown
      mechanism. We report here that Nef is detectable at moderate levels in
      preparations of HIV-1 virions which lack active viral protease (PR).
      Significantly smaller amounts of intact Nef were present in wild-type virion
      preparations. Instead, a smaller Nef-related product with an apparent molecular
      mass of 18 kDa was associated with wild-type virions, indicating that packaging
      of Nef resulted in cleavage by the viral PR. The presence of the HIV-1 PR
      inhibitor A77003 during virus production prevented the appearance of the 18-kDa
      Nef product and caused an accumulation of full-length Nef in virion preparations.
      Nef associated with comparable efficiency with viral particles produced by the
      Gag polyproteins of HIV-1 and Moloney murine leukemia virus, indicating that no
      specific interaction with a virion component is required for the incorporation of
      Nef. The N-terminal 86 amino acids of Nef were sufficient for packaging into
      virions. A nonmyristylated form of Nef associated with viral particles with
      considerably lower efficiency, suggesting that Nef gains access into nascent
      virions primarily as a consequence of its affinity for membranes. Our results
      raise the possibility that Nef enhances infectivity directly as a component of
      the virion.

PMID- 8995621
TI  - Interaction of herpes simplex virus 1 alpha regulatory protein ICP0 with
      elongation factor 1delta: ICP0 affects translational machinery.
AB  - The herpes simplex virus 1 (HSV-1)-infected cell protein 0 (ICP0) is a
      promiscuous transactivator, and by necessity, its functions must be mediated
      through cellular gene products. In an attempt to identify cellular factors
      interacting with ICP0, we used the carboxyl-terminal domain of ICP0 as "bait" in
      the yeast (Saccharomyces cerevisiae) two-hybrid system. Our results were as
      follows: (i) All 43 cDNAs in positive yeast colonies were found to encode the
      same translation factor, elongation factor delta-1 (EF-1delta). (ii) Purified
      chimeric protein consisting of glutathione S-transferase (GST) fused to EF-1delta
      specifically formed complexes with ICP0 contained in HSV-1-infected cell lysate.
      (iii) Fractionation of infected HEp-2 cells and immunofluorescence studies
      revealed that ICP0 was localized both in the nucleus and in the cytoplasm. In
      primary human foreskin fibroblasts, ICP0 was localized predominantly in the
      cytoplasm throughout HSV-1 infection even early in infection. (iv) Addition of
      the chimeric protein GST-carboxyl-terminal domain of ICP0 to the rabbit
      reticulocyte lysate in vitro translation system resulted in a dose-dependent
      decrease in protein synthesis. In contrast, GST alone or GST fused to the amino
      terminal domain of ICP0 had no effect on the in vitro translation system. (v) The
      predominant forms of EF-1delta on electrophoresis in denaturing gels have
      apparent Mrs of 38,000 and 40,000. The higher-Mr form is a minor species in mock
      infected cells, whereas in human fibroblasts and Vero cells infected with HSV-1,
      this isoform becomes dominant. These results indicate that ICP0 is present and
      may have a significant role in the cytoplasm of infected cells, possibly by
      altering the efficiency of translation of viral mRNAs.

PMID- 8995622
TI  - Functional identification of nucleotides conferring substrate specificity to
      retroviral integrase reactions.
AB  - The long terminal repeats (LTRs) that flank the retroviral DNA genome play a
      distinct role in the integration process by acting as specific substrates for the
      integrase (IN). The role of LTR sequences in providing substrate recognition and
      specificity to integration reactions was investigated for INs from human
      immunodeficiency virus type 1 (HIV-1), Moloney murine leukemia virus (M-MuLV),
      human T-cell leukemia virus type 1 (HTLV-1), and human T-cell leukemia virus type
      2 (HTLV-2). Overall, these INs required specific LTR sequences for optimal
      catalysis of 3'-processing reactions, as opposed to strand transfer and
      disintegration reactions. It is of particular note that in strand transfer
      reactions the sites of integration were similar among the four INs. In the 3'
      processing reaction, sequence specificity for each IN was traced to the three
      nucleotides proximal to the conserved CA. Reactions catalyzed by M-MuLV IN were
      additionally influenced by upstream regions. The nucleotide requirements for
      optimal catalysis differed for each IN. HIV-1 IN showed a broad range of
      substrate specificities, while HTLV-1 IN and HTLV-2 IN had more defined sequence
      requirements. M-MuLV IN exhibited greater activity with the heterologous LTR
      substrates than with its own wild-type substrate. This finding was further
      substantiated by the high levels of activity catalyzed by the IN on modified M
      MuLV LTRs. This work suggests that unlike the other INs examined, M-MuLV IN has
      evolved with an IN-LTR interaction that is suboptimal.

PMID- 8995624
TI  - Point mutations within the betaG-betaH loop of foot-and-mouth disease virus O1K
      affect virus attachment to target cells.
AB  - The amino acid sequence Arg-Gly-Asp (RGD) is a highly conserved region located on
      the P1D protein of most sero- and subtypes of foot-and-mouth disease virus
      (FMDV)and participates in binding of FMDV to their target cells. In order to
      analyze the role of the RGD sequence in FMDV infection of cells in more detail,
      13 mutations within or near the RGD sequence of virus type O1Kaufbeuren were
      designed by using a full-length cDNA plasmid. Transfection of baby hamster kidney
      cells (BHK-21) with in vitro-transcribed cRNAs containing mutations bordering the
      RGD sequence led to the production of infectious virus in most cases. In
      contrast, almost all of the mutants containing changes within the RGD sequence
      produced noninfectious viral particles indistinguishable from wild-type virus by
      electron microscopy. In order to demonstrate that these noninfectious progeny
      from the RGD mutants were defective only in their cell adsorption, the respective
      cRNAs were cotransfected together with a cRNA expressing the wild-type P1
      protein. The resulting virus particles were able to infect BHK-21 cells. These
      results demonstrate the important role of the RGD sequence in FMDV binding to
      cells but also emphasize the influence of other amino acids in the bordering
      region.

PMID- 8995623
TI  - The role of eukaryotic subtilisin-like endoproteases for the activation of human
      immunodeficiency virus glycoproteins in natural host cells.
AB  - Proteolytic activation of the precursor envelope glycoproteins gp160 of human
      immunodeficiency virus type 1 (HIV-1) and gp140 of HIV-2, a prerequisite for
      viral infection, results in the formation of gp120/gp41 and gp125/gp36,
      respectively. Cleavage is mediated by cellular proteases. Furin, a member of the
      eukaryotic subtilisin family, has been shown to be an activating protease for
      HIV. Here, we compared the presence of furin and other mammalian subtilisins in
      lymphatic cells and tissues. Northern blot analyses revealed that furin and the
      recently discovered protease LPC/PC7 were the only subtilisin-like enzymes
      transcribed in such cells. Furin was identified as an enzymatically active
      endoprotease present in different lymphocytic, as well as monocytic, cell lines.
      When expressed from vaccinia virus vectors, the proprotein convertases were
      correctly processed, transported, and secreted into the media and enzymatically
      active. Coexpression of different subtilisins with the HIV envelope precursors
      revealed that furin and LPC/PC7 are able to cleave HIV-1 gp160. Moreover, both
      enzymes proteolytically processed the envelope precursor of HIV-2. gp140 was also
      cleaved to some extent by PC1, which is not, however, present in lymphatic cells.
      Furin- and LPC/PC7-catalyzed cleavage of HIV-1 gp160 resulted in biologically
      active envelope protein. In conclusion, among the known members of the subtilisin
      family, only furin and LPC/PC7 fulfill the requirements of a protease responsible
      for in vivo activation of HIV envelope glycoproteins.

PMID- 8995625
TI  - Direct ex vivo simian immunodeficiency virus (SIV)-specific cytotoxic activity
      detected from small intestine intraepithelial lymphocytes of SIV-infected
      macaques at an advanced stage of infection.
AB  - Human immunodeficiency virus (HIV) induces a profound disorganization of the
      lymphoid tissues with marked abnormalities of the immune system at the terminal
      stage of infection. Since the digestive mucosal immune system is by far the
      largest lymphoid organ of the body, we attempted to evaluate its functional
      activity in advanced stages of simian immunodeficiency virus (SIV) infection in
      the SIV-macaque model of HIV infection. Two chronically intravenously SIV
      infected macaques, including one at the AIDS stage, were studied. Intestinal
      intraepithelial lymphocytes (IEL) were isolated, analyzed, and compared to
      lymphocytes obtained from blood, spleen, and different lymph nodes: IEL were
      predominantly CD8+ T lymphocytes expressing the alphaE beta7 integrin and lacking
      the CD28 coactivatory molecule. A direct ex vivo SIV-specific cytotoxic activity
      was prominently found in the IEL of both macaques and was weaker or absent in the
      other sites. To our knowledge, this is the first report of SIV-specific cytotoxic
      activity from small intestine IEL in SIV-infected macaques. Considering the high
      similitude of the SIV-macaque model with the HIV infection in humans, these
      results may be highly important for the pathogenesis of HIV infection and more
      generally important for the characterization and function of digestive CD8+ IEL
      population.

PMID- 8995626
TI  - Members of the nuclear receptor superfamily regulate transcription from the
      hepatitis B virus nucleocapsid promoter.
AB  - The role of members of the nuclear receptor superfamily of transcription factors
      in regulating hepatitis B virus (HBV) transcription was investigated. Hepatocyte
      nuclear factor 4 (HNF4), the retinoid X receptor (RXR), and the peroxisome
      proliferator-activated receptor (PPAR) were examined for their capacity to
      modulate the level of transcriptional activity from the four HBV promoters by
      transient-transfection analysis in the dedifferentiated hepatoma cell line,
      HepG2.1. It was found that the nucleocapsid and large surface antigen promoters
      were transactivated in the presence of HNF4 whereas the enhancer I/X gene,
      nucleocapsid, and large surface antigen promoters were transactivated in the
      presence of RXR and PPAR. Characterization of the nuclear receptors interacting
      with the nucleocapsid promoter region demonstrated that HNF4 is the primary
      transcription factor binding to the regulatory region spanning nucleotides -127
      to -102 whereas HNF4, RXR-PPAR heterodimers, COUPTF1, and ARP1 bind the
      regulatory region spanning nucleotides -34 to -7. Transcriptional transactivation
      from the nucleocapsid promoter by HNF4 appears to be mediated through the two
      HNF4 binding sites in the promoter, whereas modulation of the level of
      transcription from the nucleocapsid promoter by RXR-PPAR appears to be regulated
      by the regulatory sequence element spanning nucleotides -34 to -7 and the HBV
      enhancer 1 region. These observations indicate that HBV transcription, and
      pregenomic RNA synthesis in particular, is regulated by ligand-dependent nuclear
      receptors. Agonists and antagonists capable of regulating the activity of these
      nuclear receptors may permit the modulation of HBV transcription and consequently
      replication during viral infection.

PMID- 8995627
TI  - Oncogenesis of mammary glands, skin, and bones by polyomavirus correlates with
      viral persistence and prolonged genome replication potential.
AB  - A correlation between polyomavirus-induced oncogenesis and viral persistence on
      the one hand and/or prolonged genome replication potential on the other was
      established with respect to their respective organ distributions. Prolonged
      replication potential is defined as the capacity of a genome to replicate in a
      given organ from the time of infection up to the onset of oncogenesis. This
      conclusion was derived following intraperitoneal infection of BALB/c mice with
      wild-type strain A2. Viral genomes were used as parameters of persistence and
      replication and were detected by Southern blotting and PCR analysis. The major
      tumor target organs (mammary gland, skin, and bone), which have not been
      previously analyzed for persistence, were compared with other, non-tumor-prone
      organs (kidney, liver, lung, spleen, and salivary gland). A progressive loss of
      viral genomes was observed in all tissues as a function of time postinfection;
      however, genomes were shown to persist through 20 weeks postinfection in the
      mammary glands, skin, and bones to an extent similar to that in the previously
      described kidneys (D. J. McCance, J. Virol. 39:958-962, 1981; W. P. Rowe, J. W.
      Hartley, J. D. Estes, and R. J. Huebner, Natl. Cancer Inst. Monogr. 4:189-209,
      1960). Thus, tumors arise among organs that sustain a persistent infection, but
      not all such organs develop tumors (e.g., the kidney). The capacity of organs to
      support de novo replication at various ages, including the age reached when the
      first tumors are detected, was also determined using a 3-day infection period for
      ages between 0 and 7 weeks. For all organs tested, a higher level of genomes was
      observed in organs of mice infected as neonates than in those infected after the
      age of 3 weeks. However, marked organ-specific differences were seen in the
      degree and timing of loss of replication. In particular, viral genome
      replication, although reduced, was maintained in the mammary glands, skin, and
      bones of adult animals, in contrast to the kidneys. We conclude that organ
      specific oncogenesis correlates with two organ-specific parameters: persistence
      of viral genomes and prolonged viral genome replication potential. This may
      reflect a requirement for continued viral genome replication and/or gene
      expression for tumorigenesis. In turn, these parameters may be linked to the
      tissue-specific continued capacity for cellular division.

PMID- 8995628
TI  - The adeno-associated virus (AAV) Rep protein acts as both a repressor and an
      activator to regulate AAV transcription during a productive infection.
AB  - Adeno-associated virus (AAV) uses three promoters, p5, p19, and p40, to regulate
      viral gene expression. The p5 and p19 promoters direct the synthesis of the viral
      regulatory proteins, Rep78 and -68 and Rep52 and -40, respectively. The p5 Rep
      proteins bind a linear 22-bp sequence, the Rep binding element (RBE), that is
      within both the terminal repeat (TR) and the p5 promoter. In the absence of
      helper virus, all four Rep proteins have been shown to reduce transcription from
      the viral p5 and p19 promoters. In this report, we focus on the roles of these
      proteins and the RBEs in controlling transcription during a productive infection,
      that is, in the presence of adenovirus. We find that in the presence of
      adenovirus, the p5 RBE represses p5 transcription while the RBE in the TR
      activates p5. However, both the TR RBE and the p5 RBE transactivate the p19 and
      p40 promoters. The fact that the p5 RBE-Rep complex can transactivate p19 and p40
      while repressing p5 suggests that Rep78/68 is both a repressor and a
      transactivator. Rep repression of p5 is specific for the p5 RBE, as other p5
      promoter elements do not support this activity. We also demonstrate that in the
      presence of adenovirus, the p19 Rep proteins, which do not bind to the RBE, can
      eliminate repression of the p5 promoter by Rep78 and Rep68. This may occur by the
      association of Rep52 with Rep78 or Rep68 to produce a Rep78/68-Rep52 protein
      complex which can be detected in vivo by immunoprecipitation. Finally, two Rep
      mutants that were deficient in RBE binding and transactivation but positive for
      p5 repression were identified. These mutants may define interaction domains
      involved in making contacts with other proteins that facilitate repression. These
      observations suggest a mechanism for controlling the p5 and p19 mRNA levels
      during a productive AAV infection.

PMID- 8995629
TI  - Impaired fitness of human immunodeficiency virus type 1 variants with high-level
      resistance to protease inhibitors.
AB  - One hope to maintain the benefits of antiviral therapy against the human
      immunodeficiency virus type 1 (HIV-1), despite the development of resistance, is
      the possibility that resistant variants will show decreased viral fitness. To
      study this possibility, HIV-1 variants showing high-level resistance (up to 1,500
      fold) to the substrate analog protease inhibitors BILA 1906 BS and BILA 2185 BS
      have been characterized. Active-site mutations V32I and I84V/A were consistently
      observed in the protease of highly resistant viruses, along with up to six other
      mutations. In vitro studies with recombinant mutant proteases demonstrated that
      these mutations resulted in up to 10(4)-fold increases in the Ki values toward
      BILA 1906 BS and BILA 2185 BS and a concomitant 2,200-fold decrease in catalytic
      efficiency of the enzymes toward a synthetic substrate. When introduced into
      viral molecular clones, the protease mutations impaired polyprotein processing,
      consistent with a decrease in enzyme activity in virions. Despite these
      observations, however, most mutations had little effect on viral replication
      except when the active-site mutations V32I and I84V/A were coexpressed in the
      protease. The latter combinations not only conferred a significant growth
      reduction of viral clones on peripheral blood mononuclear cells but also caused
      the complete disappearance of mutated clones when cocultured with wild-type virus
      on T-cell lines. Furthermore, the double nucleotide mutation I84A rapidly
      reverted to I84V upon drug removal, confirming its impact on viral fitness.
      Therefore, high-level resistance to protease inhibitors can be associated with
      impaired viral fitness, suggesting that antiviral therapies with such inhibitors
      may maintain some clinical benefits.

PMID- 8995630
TI  - Phenotypic and genetic analysis of Lymantria dispar nucleopolyhedrovirus few
      polyhedra mutants: mutations in the 25K FP gene may be caused by DNA replication
      errors.
AB  - We previously demonstrated that polyhedron formation (PF) mutants arise at a high
      frequency during serial passage of the Lymantria dispar nucleopolyhedrovirus
      (LdMNPV) in the L. dispar 652Y cell line (J. M. Slavicek, N. Hayes-Plazolles, and
      M. E. Kelly, Biol. Control 5:251-261, 1995). Most of these PF mutants exhibited
      the traits of few polyhedra (FP) mutants; however, no large DNA insertions or
      deletions that correlated with the appearance of the FP phenotype were found. In
      this study, we have characterized several of the PF mutants at the phenotypic and
      genetic levels. Genetic techniques were used to group the mutations in the LdMNPV
      PF mutants to the same or closely linked genes. Wild-type viruses were recovered
      after coinfection of L. dispar 652Y cells with certain combinations of PF
      mutants. These viruses were analyzed by restriction endonuclease analysis and
      found to be chimeras of the original PF mutants used in the coinfections. Marker
      rescue experiments localized the mutations in one group of PF isolates to the
      region containing the LdMNPV 25K FP gene. The mutations in these PF mutants were
      identified. Four of five of the LdMNPV FP mutants contain small insertions or
      deletions within the 25K FP gene. The fifth LdMNPV FP mutant analyzed contained a
      large deletion that truncated the C terminus of the 25K FP gene product. All of
      the deletions occurred within the same potential hairpin loop structure, which
      had the lowest free energy value (most stable hairpin) of the five potential
      hairpin loop structures present in the 25K FP gene. One of the insertion mutants
      contained an extra base within a repetitive sequence. These types of mutations
      are likely caused by errors that occur during DNA replication. The relationship
      between the types of mutations found within the LdMNPV 25K FP gene and DNA
      replication-based mutagenesis is discussed.

PMID- 8995631
TI  - Topology of the large envelope protein of duck hepatitis B virus suggests a
      mechanism for membrane translocation during particle morphogenesis.
AB  - We have investigated the membrane topology of the large envelope protein of duck
      hepatitis B virus (DHBV) by protease protection and Western blot analysis, using
      monoclonal antibodies specific for the pre-S and S regions of the DHBV envelope
      to characterize protease-resistant polypeptides. These studies showed that DHBV L
      protein exhibits a mixed membrane topology similar to that of human hepatitis B
      virus L, with approximately half of the L molecules displaying pre-S on the
      surface of virus particles and the remainder with pre-S sequestered inside the
      virus envelope. The C-terminal region of DHBV pre-S was susceptible to protease
      digestion on all DHBV particle L protein, indicating that this region was
      externally disposed. DHBV L protein pre-S was entirely cytosolic immediately
      after synthesis. Our data, therefore, suggested that an intermediate form of the
      DHBV L molecule exists in mature envelope particles in which L is partially
      translocated or exists in a translocation-ready conformation. Incubation of virus
      particles at low pH and 37 degrees C triggered conversion of this intermediate
      into a fully translocated form. We have proposed a model for pre-S translocation
      based on our results that invokes the presence of an aqueous pore in the virus
      envelope, most likely created by oligomerization of transmembrane domains in the
      S region. The model predicts that pre-S is transported through this pore and that
      a loop structure is formed because the N terminus remains anchored to the inner
      face of the membrane. This translocation process occurs during particle
      morphogenesis and may also be a prerequisite to virus uncoating during infection.

PMID- 8995632
TI  - Structural analysis of the adenovirus type 5 E1B 55-kilodalton-E4orf6 protein
      complex.
AB  - The adenovirus type 5 (Ad5) early 1B (E1B) 55-kDa (E1B-55kDa)-E4orf6 protein
      complex has been implicated in the selective modulation of nucleocytoplasmic mRNA
      transport at late times after infection. Using a combined immunoprecipitation
      immunoblotting assay, we mapped the domains in E1B-55kDa required for the
      interaction with the E4orf6 protein in lytically infected A549 cells. Several
      domains in the 496-residue 55-kDa polypeptide contributed to a stable association
      with the E4orf6 protein in E1B mutant virus-infected cells. Linker insertion
      mutations at amino acids 180 and 224 caused reduced binding of the E4orf6
      protein, whereas linker insertion mutations at amino acid 143 and in the central
      domain of E1B-55kDa eliminated the binding of the E4orf6 protein. Earlier work
      showing that the central domain of E1B-55kDa is required for binding to p53 and
      the recent observation that the E4orf6 protein also interacts with the tumor
      suppressor protein led us to suspect that p53 might play a role in the E1B-E4
      protein interaction. However, coimmunoprecipitation assays with extracts prepared
      from infected p53-negative H1299 cells established that p53 is not needed for the
      E1B-E4 protein interaction in adenovirus-infected cells. Using two different
      protein-protein interaction assays, we also mapped the region in the E4orf6
      protein required for E1B-55kDa interaction to the amino-terminal 55 amino acid
      residues. Interestingly, both binding assays established that the same region in
      the E4orf6/7 protein can potentially interact with E1B-55kDa. Our results
      demonstrate that two distinct segments in the 55-kDa protein encoding the
      transformation and late lytic functions independently interact with p53 and the
      E4orf6 protein in vivo and provide further insight by which the multifunctional
      55-kDa EIB protein can exert its multiple activities in lytically infected cells
      and in adenovirus transformation.

PMID- 8995633
TI  - Nuclear sites of herpes simplex virus type 1 DNA replication and transcription
      colocalize at early times postinfection and are largely distinct from RNA
      processing factors.
AB  - We have visualized the intracellular localization of herpes simplex virus (HSV)
      type 1 replication and transcription sites in infected HeLa cells by using direct
      labelling methods. The number of viral transcription foci increases in a limited
      way; however, the number of replication sites increases in a near-exponential
      manner throughout infection, and both replication and transcription sites are
      found buried throughout the nuclear interior. Simultaneous visualization of viral
      transcription and replication foci shows that the two processes colocalize at
      early times, but at later times postinfection, there are additional sites
      committed solely to replication. This contrasts with the situation in adenovirus
      infected cells in which, throughout replication, sites of transcription are
      adjacent to but do not colocalize with sites of viral DNA replication. The data
      for an increase in HSV transcription sites suggest an initial phase of
      replication of input genomes which are then transcribed. Sites of HSV replication
      colocalize with viral DNA replication and packaging proteins but are largely
      distinct from the punctate distribution of small nuclear ribonucleoprotein
      particles. Very high multiplicities of infection have shown an upper limit of
      some 18 viral transcription foci per nucleus, suggesting cellular constraints on
      transcription site formation. Use of virus replication mutants confirms that the
      labelled foci are sites of viral RNA and DNA synthesis; in the absence of viral
      DNA replication functions, no replication foci and only a limited number of
      transcription foci were present. Absence of a packaging function had no apparent
      effect on transcription or replication site formation, illustrating that DNA
      packaging is not a prerequisite for ongoing DNA synthesis. Further, the essential
      HSV protein IE63 is required for efficient replication site formation at later
      times postinfection but is not required for transcription foci formation.

PMID- 8995635
TI  - A novel terminal resolution-like site in the adeno-associated virus type 2
      genome.
AB  - The adeno-associated virus 2 (AAV) contains a single-stranded DNA genome of which
      the terminal 145 nucleotides are palindromic and form T-shaped hairpin
      structures. These inverted terminal repeats (ITRs) play an important role in AAV
      DNA replication and resolution, since each of the ITRs contains a terminal
      resolution site (trs) that is the target site for the AAV rep gene products
      (Rep). However, the Rep proteins also interact with the AAV DNA sequences that
      lie outside the ITRs, and the ITRs also play a crucial role in excision of the
      proviral genome from latently infected cells or from recombinant AAV plasmids. To
      distinguish between Rep-mediated excision of the viral genome during rescue from
      recombinant AAV plasmids and the Rep-mediated resolution of the ITRs during AAV
      DNA replication, we constructed recombinant AAV genomes that lacked either the
      left or the right ITR sequence and one of the Rep-binding sites (RBSs). No rescue
      and replication of the AAV genome occurred from these plasmids following
      transfection into adenovirus type 2-infected human KB cells, as expected.
      However, excision and abundant replication of the vector sequences was clearly
      detected from the plasmid that lacked the AAV left ITR, suggesting the existence
      of an additional putative excision site in the left end of the AAV genome. This
      site was precisely mapped to one of the AAV promoters at map unit 5 (AAV p5) that
      also contains an RBS. Furthermore, deletion of this RBS abolished the rescue and
      replication of the vector sequences. These studies suggest that the Rep-mediated
      cleavage at the RBS during viral DNA replication may, in part, account for the
      generation of the AAV defective interfering particles.

PMID- 8995634
TI  - Association of herpes simplex virus regulatory protein ICP22 with transcriptional
      complexes containing EAP, ICP4, RNA polymerase II, and viral DNA requires
      posttranslational modification by the U(L)13 proteinkinase.
AB  - The expression of herpes simplex virus 1 gamma (late) genes requires functional
      alpha proteins (gamma1 genes) and the onset of viral DNA synthesis (gamma2
      genes). We report that late in infection after the onset of viral DNA synthesis,
      cell nuclei exhibit defined structures which contain two viral regulatory
      proteins (infected cell proteins 4 and 22) required for gamma gene expression,
      RNA polymerase II, a host nucleolar protein (EAP or L22) known to be associated
      with ribosomes and to bind small RNAs, including the Epstein-Barr virus small
      nuclear RNAs, and newly synthesized progeny DNA. The formation of these complexes
      required the onset of viral DNA synthesis. The association of infected cell
      protein 22, a highly posttranslationally processed protein, with these structures
      did not occur in cells infected with a viral mutant deleted in the genes U(L)13
      and U(S)3, each of which specifies a protein kinase known to phosphorylate the
      protein.

PMID- 8995636
TI  - Polarized entry and release in epithelial cells of Black Creek Canal virus, a New
      World hantavirus.
AB  - Black Creek Canal (BCC) virus is a newly identified hantavirus from Florida which
      is carried by the cotton rat (Sigmodon hispidus) and is associated with
      hantavirus pulmonary syndrome (HPS). We have investigated the interaction of BCC
      virus with polarized epithelial cells to examine whether entry and release of
      this virus occur at specific plasma membrane domains. The polarized Vero C1008
      monkey kidney cell line was grown on permeable filters and infected with BCC
      virus either through the apical or basolateral surface. As shown by indirect
      immunofluorescence and radioimmunoprecipitation analysis, cells infected through
      the apical surface demonstrated a high level of susceptibility to BCC virus
      infection. In contrast, Vero C1008 cells infected basolaterally exhibited a
      barely detectable level of BCC virus-synthesized proteins. Titration of virus
      from apical and basolateral media of infected cells has demonstrated that virus
      titers released from the apical surface are about 1,200-fold greater than the
      titer of virus released into the basolateral media. The site of BCC virus release
      from polarized cells is, therefore, different from that previously described for
      release of other members of the family Bunyaviridae and may reflect one of the
      determinants of hantavirus pathogenesis. In addition, we have shown that BCC
      viral glycoproteins are expressed at the plasma membrane on the apical surface of
      polarized cells. Electron microscopy studies of the infected cells revealed
      evidence of BCC virus budding at the plasma membrane. This strongly indicates
      that, in contrast to most other members of the Bunyaviridae, BCC virus is
      assembled at the plasma membrane. Since the same site of virus assembly was
      recently described for Sin Nombre virus, it is likely that all of the new
      American hantaviruses associated with HPS utilize this same type of virus
      maturation.

PMID- 8995637
TI  - Nuclear targeting of incoming human foamy virus Gag proteins involves a
      centriolar step.
AB  - The pathways used in the transport of retroviral genomes to the nucleus are
      poorly identified. Analyzing the intracellular localization of incoming foamy
      viruses, we have found that the Gag antigens and the viral genome accumulate in a
      distinct perinuclear domain identified as the centrosome. Colchicine treatment
      completely abolished pericentriolar targeting of human foamy virus (HFV)
      proteins, suggesting a role for microtubules in the transport of the incoming
      viral proteins to the centrioles. Finally, we demonstrate that, similarly to
      human immunodeficiency virus DNA, HFV DNA can enter the nucleus of G1/S-phase
      arrested cells, although no viral gene expression can be observed. Recent
      observations have demonstrated that foamy viruses have several features not
      shared by other retroviruses. The intracellular route of the incoming Gag
      antigens may constitute a new specificity of this class of viruses.

PMID- 8995638
TI  - Immunocytochemical analysis of Uukuniemi virus budding compartments: role of the
      intermediate compartment and the Golgi stack in virus maturation.
AB  - Previous studies have suggested that Uukuniemi virus, a bunyavirus, matures at
      the membranes of the Golgi complex. In this study we have employed
      immunocytochemical techniques to analyze in detail the budding compartment(s) of
      the virus. Electron microscopy of infected BHK-21 cells showed that virus
      particles are found in the cisternae throughout the Golgi stack. Within the
      cisternae, the virus particles were located preferentially in the dilated rims.
      This would suggest that virus budding may begin at or before the cis Golgi
      membranes. The virus budding compartment was studied further by immunoelectron
      microscopy with a pre-Golgi intermediate compartment marker, p58, and a Golgi
      stack marker protein, mannosidase II (ManII). Virus particles and budding virus
      were detected in ManII-positive Golgi stack membranes and, interestingly, in both
      juxtanuclear and peripheral p58-positive elements of the intermediate
      compartment. In cells incubated at 15 degrees C the nucleocapsid and virus
      envelope proteins were seen to accumulate in the intermediate compartment.
      Immunoelectron microscopy demonstrated that at 15 degrees C the nucleocapsid is
      associated with membranes that show a characteristic distribution and tubulo
      vesicular morphology of the pre-Golgi intermediate compartment. These membranes
      contained virus particles in the lumen. The results indicate that the first site
      of formation of Uukuniemi virus particles is the pre-Golgi intermediate
      compartment and that virus budding continues in the Golgi stack. The results
      raise questions about the intracellular transport pathway of the virus particles,
      which are 100 to 120 nm in diameter and are therefore too large to be transported
      in the 60-nm-diameter vesicles postulated to function in the intra-Golgi
      transport. The distribution of the virus in the Golgi stack may imply that the
      cisternae themselves have a role in the vectorial transport of virus particles.

PMID- 8995639
TI  - Human T-cell lymphotropic virus type 1 (HTLV-1)-induced syncytium formation
      mediated by vascular cell adhesion molecule-1: evidence for involvement of cell
      adhesion molecules in HTLV-1 biology.
AB  - While studying the potential role of vascular cell adhesion molecule-1 (VCAM-1)
      in infection of endothelial cells by human immunodeficiency virus (HIV), we found
      that VCAM-1 can mediate human T-cell lymphotropic virus type 1 (HTLV-1)-induced
      syncytium formation. Both expression-vector-encoded and endogenously expressed
      VCAM-1 supported fusion of uninfected cells with HTLV-1-infected cells. Fusion
      was obtained with cell lines carrying the HTLV-1 genome and expressing viral
      proteins but not with an HTLV-1-transformed cell line that does not express viral
      proteins. In clones of VCAM-1-transfected cells, the degree of syncytium
      formation observed directly reflected the level of VCAM-1 expression. Syncytium
      formation between HTLV-1-expressing cells and VCAM-1+ cells could be blocked with
      antiserum against HTLV-1 gp46 and with a monoclonal antibody (MAb) against VCAM
      1. Fusion was not blocked by antiserum against HIV or a MAb against VLA-4, the
      physiological counter-receptor for VCAM-1. The results indicate that VCAM-1 can
      serve as an accessory molecule or potential coreceptor for HTLV-1-induced cell
      fusion and provide direct evidence of a role for cell adhesion molecules in the
      biology of HTLV-1.

PMID- 8995640
TI  - Human T-cell leukemia virus type 1 Tax transactivates the human proliferating
      cell nuclear antigen promoter.
AB  - The human T-cell leukemia virus type 1 (HTLV-1) transforming protein, Tax, is a
      potent transactivator of both viral and cellular gene expression. The ability of
      Tax to transform cells is believed to depend on its transactivation of cellular
      growth-regulatory genes. Expression of proliferating cell nuclear antigen (PCNA)
      is intimately linked to cell growth and DNA replication and repair. By testing a
      series of PCNA promoter deletion constructs, we have demonstrated that the PCNA
      promoter can be transactivated by Tax. The smallest construct that was activated
      did not include the ATF/CRE binding site at nucleotide -50, and mutations in the
      ATF/CRE element in the context of a larger promoter were still activated by Tax.
      In addition, a Tax mutant that is defective for activation of the CRE pathway
      retained the ability to activate the -397 promoter construct. When a series of
      linker scanner mutations that span the region from nucleotide -45 to -7 were
      assayed, mutations in and around a repeat sequence were found to abolish Tax
      transactivation. Multimerized copies of either half of the repeat were Tax
      responsive. A single protein complex was shown to bind specifically to the Tax
      responsive region, and the binding of this complex was enhanced in the presence
      of Tax. These results demonstrate that the PCNA promoter contains a Tax
      responsive element located between nucleotides -45 and -7 whose sequence is
      different from those of other, previously identified Tax-responsive elements. The
      ability of Tax to activate the PCNA promoter may play an important role in
      cellular transformation by HTLV-1.

PMID- 8995641
TI  - Complementation of a primer binding site-impaired murine leukemia virus-derived
      retroviral vector by a genetically engineered tRNA-like primer.
AB  - Reverse transcription of retroviral genomes is primed by a tRNA annealed to an 18
      nucleotide primer binding site. Here, we present a primer complementation system
      to study molecular interaction of the replication machinery with the primer and
      primer binding site in vivo. Introduction of eight base substitutions into the
      primer binding site of a murine leukemia virus-based vector allowed efficient RNA
      encapsidation but resulted in severely reduced vector replication capacity.
      Replication was restored upon complementation with a synthetic gene designed to
      encode a complementary tRNA-like primer, but not with a noncomplementary tRNA
      like molecule. The engineered primer was shown to be involved in both the
      initiation of first-strand synthesis and second-strand transfer. These results
      provide an in vivo demonstration that the retroviral replication machinery may
      recognize sequence complementarity rather than actual primer binding site and 3'
      primer sequences. Use of mutated primer binding site vectors replicating via
      engineered primers may add additional control features to retroviral gene
      transfer technology.

PMID- 8995643
TI  - Characterization of ribonucleoprotein complexes containing an abundant
      polyadenylated nuclear RNA encoded by Kaposi's sarcoma-associated herpesvirus
      (human herpesvirus 8).
AB  - Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) (also called human
      herpesvirus 8) is strongly linked to all forms of Kaposi's sarcoma. We have
      previously identified two polyadenylated KSHV transcripts that are actively
      transcribed in Kaposi's sarcoma (KS) tumors and in KSHV-infected B-lymphoma
      cells. One of these RNAs (termed T1.1 or nut-1 RNA) is a 1.1-kb transcript
      present in a subpopulation of KS tumor cells. This RNA is localized to the
      nucleus of infected cells and has no open reading frames longer than 62 codons,
      suggesting that it may not function as an mRNA in vivo. Here we demonstrate that
      nut-1 RNA is a lytic-cycle gene product that is found in high-molecular-weight
      ribonucleoprotein complexes in infected cell nuclei. The transcript lacks the
      trimethylguanosine (TMG) cap found in many U-like small nuclear RNAs, but a
      subpopulation of nut-1 RNAs can associate with Sm protein-containing small
      nuclear ribonucleoproteins, as judged by immunoprecipitation analyses using
      monoclonal anti-Sm and anti-TMG antibodies. This interaction does not require
      other viral gene products, and deletion of the sole candidate Sm binding site on
      nut-1 RNA does not ablate this association. This finding suggests an indirect
      interaction with Sm-containing structures, and models for such associations are
      presented.

PMID- 8995642
TI  - Second-site proviral enhancer alterations in lymphomas induced by enhancer
      mutants of SL3-3 murine leukemia virus: negative effect of nuclear factor 1
      binding site.
AB  - SL3-3 is a highly T-lymphomagenic murine retrovirus. Previously, mutation of
      binding sites in the U3 repeat region for the AML1 transcription factor family
      (also known as core binding factor [CBF], polyomavirus enhancer binding protein 2
      [PEBP2], and SL3-3 enhancer factor 1 [SEF1]) were found to strongly reduce the
      pathogenicity of SL3-3 (B. Hallberg, J. Schmidt, A. Luz, F. S. Pedersen, and T.
      Grundstrom, J. Virol. 65:4177-4181, 1991). We have now examined the few cases in
      which tumors developed harboring proviruses that besides the AML1 (core) site
      mutations carried second-site alterations in their U3 repeat structures. In three
      distinct cases we observed the same type of alteration which involved deletions
      of regions known to contain binding sites for nuclear factor 1 (NF1) and the
      addition of extra enhancer repeat elements. In transient-expression experiments
      in T-lymphoid cells, these new U3 regions acted as stronger enhancers than the U3
      regions of the original viruses. This suggests that the altered proviruses
      represent more-pathogenic variants selected for in the process of tumor
      formation. To analyze the proviral alterations, we generated a series of
      different enhancer-promoter reporter constructs. These constructs showed that the
      additional repeat elements are not critical for enhancer strength, whereas the
      NF1 sites down-regulate the level of transcription in T-lymphoid cells whether or
      not the AML1 (core) sites are functional. We therefore also tested SL3-3 viruses
      with mutated NF1 sites. These viruses have unimpaired pathogenic properties and
      thereby distinguish SL3-3 from Moloney murine leukemia virus.

PMID- 8995644
TI  - Importance of a c-Myb binding site for lymphomagenesis by the retrovirus SL3-3.
AB  - All murine leukemia viruses (MuLVs) and related type C retroviruses contain a
      highly conserved binding site for the Ets family of transcription factors within
      the enhancer sequences in the viral long terminal repeats (LTRs). The T-cell
      lymphomagenic MuLV SL3-3 (SL3-3) also contains a c-Myb binding site adjacent to
      the Ets site. The presence of this Myb site distinguishes SL3 from most other
      MuLVs. We tested the importance of these two sites for the lymphomagenicity of
      SL3-3. Mutation of the Ets site had little effect on viral pathogenicity, as it
      only slightly extended the latency period to disease onset. In contrast, mutation
      of the Myb site strongly inhibited pathogenicity, as only a minority of the
      inoculated mice developed tumors in the two mouse strains that were tested. All
      tumors that were induced by either mutant appeared to be lymphomas, and no
      evidence for reversion of either mutation was detected. The effects of the Ets
      and Myb site mutations on transcriptional activity of the SL3 LTR were tested by
      inserting the viral enhancer sequences into a plasmid containing the promoter
      region of the c-myc gene linked to a reporter gene. Mutation the Myb site almost
      eliminated enhancer activity in T lymphocytes, while mutation of the Ets site had
      smaller effects. Thus, the effects of the enhancer mutations on transcriptional
      activity in T cells paralleled their effects on viral lymphomagenicity. The
      absence of the c-Myb site in the LTR enhancer of the weakly lymphomagenic MuLV,
      Akv, likely contributes to the low pathogenicity of this virus relative to SL3-3.
      However, Moloney MuLV also lacks the Myb site in its LTR, although it induces T
      cell lymphomas with a potency similar to that of SL3-3. Thus, it appears that SL3
      3 and Moloney MuLV evolved genetic determinants of T-cell lymphomagenicity that
      are, at least in part, distinct.

PMID- 8995645
TI  - Inhibition of host cell transcription by poliovirus: cleavage of transcription
      factor CREB by poliovirus-encoded protease 3Cpro.
AB  - Host cell RNA polymerase II-mediated transcription is inhibited by poliovirus
      infection. Previous studies from our laboratory showed that activated
      transcription from a cyclic AMP-responsive element (CRE)-containing promoter was
      severely inhibited in extracts prepared from poliovirus-infected HeLa cells
      compared to those from mock-infected cells. Here we demonstrate that the CRE
      binding protein, CREB, is specifically cleaved by the poliovirus-encoded protease
      3Cpro both in vitro and in virus-infected cells. The proteolytic cleavage of CREB
      leads to a significant loss of its DNA binding as well as transcriptional
      activity. Additionally, we demonstrate that the phosphorylated, transcriptionally
      active form of CREB is cleaved by the viral protease in vitro. The results
      presented here suggest that a direct cleavage of CREB by the viral protease 3Cpro
      leads to inhibition of CREB-activated transcription in poliovirus-infected HeLa
      cells.

PMID- 8995646
TI  - Early cytokine and chemokine gene expression in lymph nodes of macaques infected
      with simian immunodeficiency virus is predictive of disease outcome and vaccine
      efficacy.
AB  - Competitive PCR was used to evaluate the expression of cytokine, granzyme B, and
      chemokine genes in lymph nodes of macaques recently infected with the simian
      immunodeficiency virus (SIV) pathogenic molecular clone SIVmac239 (n = 16), the
      nonpathogenic vaccine strain SIVmac239 delta nef (n = 8), and the nonpathogenic
      molecular clone SIVmac1A11 (n = 8). For both SIVmac239 and its nef-deleted
      derivative, strong expression was observed as early as 7 days postinfection for
      interleukin 1beta (IL-1beta), IL-6, tumor necrosis factor alpha, gamma
      interferon, and IL-13. The levels of gene induction were equally intense for both
      viruses despite a lower viral load for SIVmac239 deltanef compared with that for
      SIVmac239. However, the nature of the cytokine network activation varied with the
      viral inocula. Primary infection with SIVmac239 was characterized by a higher
      level of IL-4, IL-10, MIP-1alpha, MIP-1beta, MCP-1, and RANTES gene expression
      and a lower level of IL-12 and granzyme B gene expression compared with infection
      with SIVmac239 delta nef. Thus, infection with nef-deleted SIV was associated
      with a preferential Th1 versus Th2 pattern of cytokine production. Infection with
      SIVmac1A11 was characterized by a delayed immune response for all markers tested.
      The unique patterns of cytokine and chemokine gene expression in lymph nodes
      correlated nicely with the pathogenic potential of the SIV strains used as well
      as with differences in their ability to serve as protective vaccines.

PMID- 8995647
TI  - Shared promoter elements between a viral superantigen and the major
      histocompatibility complex class II-associated invariant chain.
AB  - Superantigens have the ability to stimulate subsets of T lymphocytes bearing
      particular T-cell receptor Vbeta chains. The best-known viral superantigen is
      Mls, a product of the murine mammary tumor virus (MMTV) sag gene. The MMTV
      superantigen is not displayed by the virus itself; however, after infection of B
      lymphocytes, the superantigen is expressed. The resulting immune stimulation is
      essential for viral transmission. We have analyzed the transcriptional elements
      which control Mls-1 expression. Here we present evidence that a region at the 3'
      end of Mtv-7 env, Penv2, controls B-cell-specific expression of sag. Penv2 has
      elements homologous with promoters of immunoglobulin H chain, the invariant
      chain, and major histocompatibility complex class II, suggesting a coordinate
      regulation of expression of these various B-cell-specific genes and indicating a
      possible eukaryotic origin of MMTV sag. We have determined that both an IgH
      heptamer element and a Y box are essential for Penv2 promoter activity and that
      tandem octamer motifs in the U3 region of the 3' MMTV long terminal repeat
      function as enhancers. We propose that Penv2 controls constitutive Mls expression
      in B lymphocytes.

PMID- 8995648
TI  - Effect of a modulator deletion on transcription of the human cytomegalovirus
      major immediate-early genes in infected undifferentiated and differentiated
      cells.
AB  - Differentiation-dependent expression of the human cytomegalovirus (HCMV) major
      immediate-early (MIE) genes, encoding IE1 and IE2, may partly govern virus
      replication in monocytic THP-1 and embryonal carcinoma (Tera-2) cells. The
      modulator of the MIE promoter was shown previously in transient transfection
      assays to repress transcription from promoter segments in undifferentiated THP-1
      and Tera-2 cells but not in differentiated cells. To determine the biological
      importance of these findings, we constructed a recombinant HCMV (r delta MSVgpt)
      without a modulator. In comparison to wild-type (WT) virus, r delta MSVgpt
      exhibits a slight delay in growth in human fibroblasts, but there is no
      appreciable change in IE1 and IE2 transcription. Moreover, there is no
      appreciable change in the early/late kinetics of transcription of RNAs colinear
      with the predicted UL128 coding region, which is adjacent to the modulator,
      although the size distribution and abundance of these RNAs are altered. In
      infected undifferentiated THP-1 and Tera-2 cells, WT and r alpha MSVgpt viruses
      produce minimal but comparable amounts of IE1 RNAs. The genomes of both viruses
      are detectable in similar amounts within these undifferentiated cells. Induction
      of cellular differentiation before infection overcomes the block in MIE gene
      transcription. WT and r alpha MSVgpt infections of differentiated THP-1 cells
      produce similar levels of IE1 and IE2 RNAs. Thus, differentiation-dependent
      control of MIE gene transcription involves regulatory mechanisms other than the
      modulator. Possible alternative functions of the modulator are discussed.

PMID- 8995649
TI  - Overlapping epitopes in human immunodeficiency virus type 1 gp120 presented by
      HLA A, B, and C molecules: effects of viral variation on cytotoxic T-lymphocyte
      recognition.
AB  - Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) are
      thought to exert immunologic selection pressure in infected persons, yet few data
      regarding the effects of this constraint on viral sequence variation in vivo,
      particularly in the highly variable Env protein, are available. In this study,
      CD8+ HIV type 1 (HIV-1) envelope-specific CTL clones specific for gp120 were
      isolated from peripheral blood mononuclear cells of four HIV-infected
      individuals, all of which recognized the same 25-amino-acid (aa) peptide (aa 371
      to 395), which is partially contained in the CD4-binding domain of HIV-1 gp120.
      Fine mapping studies revealed that two of the clones optimally recognized the 9
      aa sequence 375 to 383 (SFNCGGEFF), while the two other clones optimally
      recognized the epitope contained in the overlapping 9-aa sequence 376 to 384
      (FNCGGEFFY). Lysis of target cells by the two clones recognizing aa 375 to 383
      was restricted by HLA B15 and Cw4, respectively, whereas both clones recognizing
      aa 376 to 384 were restricted by HLA A29. Sequence variation, relative to the
      IIIB strain sequence used to identify CTL clones, was observed in autologous
      viruses in the epitope-containing region in all four subjects. However, poorly
      recognized autologous sequence variants were predominantly seen for the A29
      restricted clones, whereas the clones specific for SFNCGGEFF continued to
      recognize the predominant autologous sequences. These results suggest that the
      HLA profile of an individual may not only be important in determining the
      specificity of CTL recognition but may also affect the ability to recognize virus
      variants and suppress escape from CTL recognition. These results also identify
      overlapping viral CTL epitopes which can be presented by HLA A, B, and C
      molecules.

PMID- 8995650
TI  - Rescue of rinderpest virus from cloned cDNA.
AB  - Rinderpest virus is a morbillivirus and is the causative agent of a widespread
      and important disease of cattle. The viral genome is a single strand of RNA in
      the negative sense. We have constructed plasmids containing cDNA copies of the 5'
      and 3' termini of the virus separated by a reporter gene and have shown that
      antigenome-sense RNA transcripts of these model genomes can be replicated,
      transcribed, and packaged by helper virus, both rinderpest virus and the related
      measles virus. Further, these genome analogs can be replicated and transcribed by
      viral proteins expressed from cDNA clones by using a recombinant vaccinia virus
      expressing T7 RNA polymerase (MVA-T7). Using this latter system, we have rescued
      live rinderpest virus from a full-length cDNA copy of the genome of the RBOK
      vaccine strain. The recombinant virus appears to grow in tissue culture
      identically to the original virus.

PMID- 8995651
TI  - Investigation of the dynamics of the spread of human immunodeficiency virus to
      brain and other tissues by evolutionary analysis of sequences from the p17gag and
      env genes.
AB  - The time of spread of human immunodeficiency virus type 1 (HIV-1) from lymphoid
      to nonlymphoid tissues in the course of infection was investigated by sequence
      comparisons of variants infecting a range of lymphoid and nonlymphoid tissues
      from three individuals with AIDS in the pl7gag gene and regions flanking the
      V1/V2 hypervariable regions. Phylogenetic analysis in both regions revealed
      several lineages in each individual that contained sequences from both lymphoid
      and nonlymphoid tissues such as the brain. This observation contrasts strongly
      with the previously described organ-specific sequences in the V3 region in this
      study population and other investigations. Although individual pairwise
      comparisons of relatively short sequences such as p17gag are subject to
      considerable stochastic error, we found that the diversity of gag sequences in
      variants from lymphoid tissue was consistently lower than that found among
      variants amplified from the brain. By estimating mean synonymous pairwise
      distances in the p17gag region, we were able to make an approximate calculation
      of the ages of populations in different tissues. Those from lymphoid tissue
      ranged from 2.65 to 5.6 years in the three study subjects, compared with 4.1 to
      6.2 years for variants in the brain. Indeed, variants infecting the brain were no
      more closely related to each other than they were to variants infecting other
      tissues in the body. In two of the three individuals, these times of divergence
      indicate that infection of the brain may have occurred as an early event in the
      progression to disease, preceding the onset of AIDS by several years. This study
      is the first in which it was possible to estimate times of diversification in
      different tissues in vivo and is of importance in understanding the dynamics of
      the spread of HIV-1 into nonlymphoid tissues and its possible adaptation for
      replication in different cell types.

PMID- 8995652
TI  - Assembly of herpes simplex virus capsids using the human cytomegalovirus scaffold
      protein: critical role of the C terminus.
AB  - An essential step in assembly of herpes simplex virus (HSV) type 1 capsids
      involves interaction of the major capsid protein (VP5) with the C terminus of the
      scaffolding protein (encoded by the UL26.5 gene). The final 12 residues of the
      HSV scaffolding protein contains an A-X-X-F-V/A-X-Q-M-M-X-X-R motif which is
      conserved between scaffolding proteins found in other alphaherpesviruses but not
      in members of the beta- or gamma-herpesviruses. Previous studies have shown that
      the bovine herpesvirus 1 (alphaherpesvirus) UL26.5 homolog will functionally
      substitute for the HSV UL26.5 gene (E. J. Haanes et al., J. Virol. 69:7375-7379,
      1995). The homolog of the UL26.5 gene in the human cytomegalovirus (HCMV) genome
      is the UL80.5 gene. In these studies, we tested whether the HCMV UL80.5 gene
      would substitute for the HSV UL26.5 gene in a baculovirus capsid assembly system
      that we have previously described (D. R. Thomsen et al., J. Virol. 68:2442-2457,
      1994). The results demonstrate that (i) no intact capsids were assembled when the
      full-length or a truncated (missing the C-terminal 65 amino acids) UL80.5 protein
      was tested; (ii) when the C-terminal 65 amino acids of the UL80.5 protein were
      replaced with the C-terminal 25 amino acids of the UL26.5 protein, intact capsids
      were made and direct interaction of the UL80.5 protein with VP5 was detected;
      (iii) assembly of intact capsids was demonstrated when the sequence of the last
      12 amino acids of the UL80.5 protein was changed from RRIFVA ALNKLE to
      RRIFVAAMMKLE; (iv) self-interaction of the scaffold proteins is mediated by
      sequences N terminal to the maturation cleavage site; and (v) the UL26.5 and
      UL80.5 proteins will not coassemble into scaffold structures. The results suggest
      that the UL26.5 and UL80.5 proteins form a scaffold by self-interaction via
      sequences in the N termini of the proteins and emphasize the importance of the C
      terminus for interaction of scaffold with the proteins that form the capsid
      shell.

PMID- 8995653
TI  - Mother-to-infant transmission of human immunodeficiency virus type 1 involving
      five envelope sequence subtypes.
AB  - Genetic analysis of human immunodeficiency virus type 1 (HIV-1) from cases of
      mother-to-infant transmission were analyzed in an effort to provide insights into
      the viral selection that may occur during transmission, as well as the timing and
      source of transmitted viruses. HIV-1 env genes obtained from seven mothers and
      their perinatally infected infants in Sweden were studied. Five envelope sequence
      clades (A to E) were found to be represented. We used a heteroduplex tracking
      assay (HTA) to assess the genetic relatedness between early viral isolates from
      the infants and serial maternal virus populations taken during pregnancy and at
      delivery. HTA findings were used to select for DNA sequence analysis maternal
      virus populations that were either closely or more distantly related to the
      infant virus. In each case, nucleotide sequence analysis confirmed the genetic
      relationships inferred by the HTA. Only maternal peripheral blood was sampled,
      and large sets of maternal specimens throughout pregnancy were generally not
      available. However, no consistent correlation was found to support the hypothesis
      that infant viruses should match blood-derived maternal virus genotypes found
      early in pregnancy if infants were found to be infected at birth or, conversely,
      that infant viruses should match blood-derived maternal virus genotypes found at
      delivery if infants were found to be infected only some time later.

PMID- 8995654
TI  - Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin
      beta receptor.
AB  - Hepatitis C virus (HCV) core protein is a multifunctional protein. We examined
      whether it can interact with cellular proteins, thus contributing to viral
      pathogenesis. Using the HCV core protein as a bait to screen a human liver cDNA
      library in a yeast two-hybrid screening system, we have isolated several positive
      clones encoding cellular proteins that interact with the HCV core protein.
      Interestingly, more than half of these clones encode the cytoplasmic domain of
      lymphotoxin-beta receptor (LT betaR), which is a member of the tumor necrosis
      factor receptor family. Their binding was confirmed by in vitro glutathione S
      transferase fusion protein binding assay and protein-protein blotting assay to be
      direct and specific. The binding sites were mapped within a 58-amino-acid region
      of the cytoplasmic tail of LT betaR. The binding site in the HCV core protein was
      localized within amino acid residues 36 to 91 from the N terminus, corresponding
      to the hydrophilic region of the protein. In mammalian cells, the core protein
      was found to be associated with the membrane-bound LT betaR. Since the LT betaR
      is involved in germinal center formation and developmental regulation of
      peripheral lymphoid organs, lymph node development, and apoptotic signaling, the
      binding of HCV core protein to LT betaR suggests the possibility that this viral
      protein has an immunomodulating function and may explain the mechanism of viral
      persistence and pathogenesis of HCV.

PMID- 8995655
TI  - In vitro model for the nuclear transport of the hepadnavirus genome.
AB  - Hepadnaviruses contain a DNA genome, but they replicate via an RNA intermediate,
      synthesized by the cellular RNA polymerase II in the nucleus of the infected
      cell. Thus, nuclear transport of the viral DNA is required in the viral life
      cycle. Protein-free DNA is only poorly imported into the nucleus, so one or more
      of the viral proteins must be involved in the transport of the viral genome. In
      order to identify these viral proteins, we purified woodchuck hepadnavirus (WHV)
      core particles from infected woodchuck liver, isolated WHV DNA, and extracted the
      covalent complex of viral polymerase from the particles using urea. Intact core
      particles, the polymerase-DNA complex, or protein-free WHV DNA from core
      particles was added to digitonin-permeabilized HuH-7 cells, in which the cytosol
      was substituted by rabbit reticulocyte lysate (RRL) and an ATP-generating system.
      The distribution of the viral genome was analyzed by semiquantitative PCR or by
      hybridization in total nuclei, RRL, nuclear membranes, and nucleoplasm. The
      polymerase-DNA complex was efficiently transported into the nucleus, as indicated
      by the resistance of the nucleus-associated DNA to a short-term treatment with
      DNase I of the intact nuclei. The DNA within core particles stayed mainly in the
      cytosol and remained protected against DNase I. A minor part of the encapsidated
      DNA was bound to nuclei. It was protected against DNase I but became accessible
      after disruption of the nuclei. Deproteinized viral DNA completely remained in
      the cytosol. These data show that the viral polymerase is probably sufficient for
      mediating the transport of a hepadnavirus genome into the nucleus and that the
      viral core particles may release the genome at the nuclear membrane.

PMID- 8995656
TI  - Molecular epidemiology of 58 new African human T-cell leukemia virus type 1 (HTLV
      1) strains: identification of a new and distinct HTLV-1 molecular subtype in
      Central Africa and in Pygmies.
AB  - To gain new insights on the origin, evolution, and modes of dissemination of
      human T-cell leukemia virus type I (HTLV-1), we performed a molecular analysis of
      58 new African HTLV-1 strains (18 from West Africa, 36 from Central Africa, and 4
      from South Africa) originating from 13 countries. Of particular interest were
      eight strains from Pygmies of remote areas of Cameroon and the Central African
      Republic (CAR), considered to be the oldest inhabitants of these regions. Eight
      long-term activated T-cell lines producing HTLV-1 gag and env antigens were
      established from peripheral blood mononuclear cell cultures of HTLV-1
      seropositive individuals, including three from Pygmies. A fragment of the env
      gene encompassing most of the gp21 transmembrane region was sequenced for the 58
      new strains, while the complete long terminal repeat (LTR) region was sequenced
      for 9 strains, including 4 from Pygmies. Comparative sequence analyses and
      phylogenetic studies performed on both the env and LTR regions by the neighbor
      joining and DNA parsimony methods demonstrated that all 22 strains from West and
      South Africa belong to the widespread cosmopolitan subtype (also called HTLV-1
      subtype A). Within or alongside the previously described Zairian cluster (HTLV-1
      subtype B), we discovered a number of new HTLV-1 variants forming different
      subgroups corresponding mainly to the geographical origins of the infected
      persons, Cameroon, Gabon, and Zaire. Six of the eight Pygmy strains clustered
      together within this Central African subtype, suggesting a common origin.
      Furthermore, three new strains (two originating from Pygmies from Cameroon and
      the CAR, respectively, and one from a Gabonese individual) were particularly
      divergent and formed a distinct new phylogenetic cluster, characterized by
      specific mutations and occupying in most analyses a unique phylogenetic position
      between the large Central African genotype (HTLV-1 subtype B) and the Melanesian
      subtype (HTLV-1 subtype C). We have tentatively named this new HTLV-1 genotype
      HTLV-1 subtype D. While the HTLV-1 subtype D strains were not closely related to
      any known African strain of simian T-cell leukemia virus type 1 (STLV-1), other
      Pygmy strains and some of the new Cameroonian and Gabonese HTLV-1 strains were
      very similar (>98% nucleotide identity) to chimpanzee STLV-1 strains, reinforcing
      the hypothesis of interspecies transmission between humans and monkeys in Central
      Africa.

PMID- 8995658
TI  - Subcellular compartmentalization of adeno-associated virus type 2 assembly.
AB  - Using immunofluorescence and in situ hybridization techniques, we studied the
      intracellular localization of adeno-associated virus type 2 (AAV-2) Rep proteins,
      VP proteins, and DNA during the course of an AAV-2/adenovirus type 2 coinfection.
      In an early stage, the Rep proteins showed a punctate distribution pattern over
      the nuclei of infected cells, reminiscent of replication foci. At this stage, no
      capsid proteins were detectable. At later stages, the Rep proteins were
      distributed more homogeneously over the nuclear interior and finally became
      redistributed into clusters slightly enriched at the nuclear periphery. During an
      intermediate stage, they also appeared at an interior part of the nucleolus for a
      short period, whereas most of the time the nucleoli were Rep negative. AAV-2 DNA
      colocalized with the Rep proteins. All three capsid proteins were strongly
      enriched in the nucleolus in a transient stage of infection, when the Rep
      proteins homogeneously filled the nucleoplasm. Thereafter, they became
      distributed over the whole nucleus and colocalized in nucleoplasmic clusters with
      the Rep proteins and AAV-2 DNA. While VP1 and VP2 strongly accumulated in the
      nucleus, VP3 was almost equally distributed between the nucleus and cytoplasm.
      Capsids, visualized by a conformation-specific antibody, were first detectable in
      the nucleoli and then spread over the whole nucleoplasm. This suggests that
      nucleolar components are involved in initiation of capsid assembly whereas DNA
      packaging occurs in the nucleoplasm. Expression of a transfected full-length AAV
      2 genome followed by adenovirus infection showed all stages of an AAV
      2/adenovirus coinfection, whereas after expression of the cap gene alone, capsids
      were restricted to the nucleoli and did not follow the nuclear redistribution
      observed in the presence of the whole AAV-2 genome. Coexpression of Rep proteins
      released the restriction of capsids to the nucleolus, suggesting that the Rep
      proteins are involved in nuclear redistribution of AAV capsids during viral
      infection. Capsid formation was dependent on the concentration of expressed
      capsid protein.

PMID- 8995657
TI  - 3'-end processing and kinetics of 5'-end joining during retroviral integration in
      vivo.
AB  - Retroviral replication depends on integration of viral DNA into a host cell
      chromosome. Integration proceeds in three steps: 3'-end processing, the
      endonucleolytic removal of the two terminal nucleotides from each 3' end of the
      viral DNA; strand transfer, the joining of the 3' ends of viral DNA to host DNA;
      and 5'-end joining (or gap repair), the joining of the 5' ends of viral DNA to
      host DNA. The 5'-end joining step has never been investigated, either for
      retroviral integration or for any other transposition process. We have developed
      an assay for 5'-end joining in vivo and have examined the kinetics of 5'-end
      joining for Moloney murine leukemia virus (MLV). The interval between 3'-end and
      5'-end joining is estimated to be less than 1 h. This assay will be a useful tool
      for examining whether viral or host components mediate 5'-end joining. MLV
      integrates its DNA only after its host cell has completed mitosis. We show that
      the extent of 3'-end processing is the same in unsynchronized and aphidicolin
      arrested cells. 3'-end processing therefore does not depend on mitosis.

PMID- 8995659
TI  - Marek's disease virus latency-associated transcripts belong to a family of
      spliced RNAs that are antisense to the ICP4 homolog gene.
AB  - Marek's disease virus (MDV) latency-associated transcripts include at least two
      MDV small RNAs (MSRs) and a 10-kb RNA which map antisense to the ICP4 homolog
      gene and are relatively abundant in MDV-transformed lymphoblastoid cells. This
      report further describes the biological and structural properties of these RNAs.
      First, these RNAs were detected in primary lymphomas isolated from chickens
      infected with several oncogenic MDV strains. Second, the MSRs are
      nonpolyadenylated, whereas, the 10-kb RNA is predominantly polyadenylated. Third,
      MSRs localize to the nuclei of both lymphoblastoid cells and cytolytically
      infected chicken embryo fibroblasts. Fourth, the 3'-region splice junctions of
      the MSRs during latent and productive infection were determined by sequencing RNA
      PCR products generated with primers that flank the 3' splice region. The MSRs
      contain at least three introns, the largest of which overlaps the ICP4 putative
      translational start site. Fifth, the 5' end of the MSRs initiates approximately 5
      kb upstream from the main body of the RNA. The extreme 5' exon is approximately
      251 nucleotides (nt) long and is joined to the main body of the transcript upon
      removal of a 4,852-nt intron. Finally, the 10-kb RNA lies entirely within the
      repeats flanking the unique short region of the genome. We believe that the MSRs
      and 10-kb RNA belong to a family of spliced RNAs that map antisense to the ICP4
      gene and comprise a complex transcriptional unit expressed during MDV-induced T
      cell transformation.

PMID- 8995660
TI  - Reovirus variants selected during persistent infections of L cells contain
      mutations in the viral S1 and S4 genes and are altered in viral disassembly.
AB  - Reoviruses isolated from persistently infected cultures (PI viruses) can grow in
      the presence of ammonium chloride, a weak base that blocks acid-dependent
      proteolysis of viral outer-capsid proteins during viral entry into cells. We used
      reassortant viruses isolated from crosses of wild-type (wt) reovirus strain, type
      1 Lang, and three independent PI viruses, L/C, PI 2A1, and PI 3-1, to identify
      viral genes that segregate with the capacity of PI viruses to grow in cells
      treated with ammonium chloride. Growth of reassortant viruses in ammonium
      chloride-treated cells segregated with the S1 gene of L/C and the S4 gene of PI
      2A1 and PI 3-1. The S1 gene encodes viral attachment protein sigma1, and the S4
      gene encodes outer-capsid protein sigma3. To identify mutations in sigma3
      selected during persistent reovirus infection, we determined the S4 gene
      nucleotide sequences of L/C, PI 2A1, PI 3-1, and four additional PI viruses. The
      deduced amino acid sequences of sigma3 protein of six of these PI viruses
      contained a tyrosine-to-histidine substitution at residue 354. To determine
      whether mutations selected during persistent infection alter cleavage of the
      viral outer capsid, the fate of viral structural proteins was assessed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis after treatment of virions of
      wt and PI viruses with chymotrypsin in vitro. Proteolysis of PI virus outer
      capsid proteins sigma3 and mu1C occurred with faster kinetics than proteolysis of
      wt virus outer-capsid proteins. These results demonstrate that mutations in
      either the S1 or S4 gene alter acid-dependent disassembly of the reovirus outer
      capsid and suggest that increased efficiency of proteolysis of viral outer-capsid
      proteins is important for maintenance of persistent reovirus infections of
      cultured cells.

PMID- 8995661
TI  - Hyper-antigenic variation occurs with human rhinovirus type 17.
AB  - Of 90 human rhinovirus (RV) serotypes tested, 50 can be placed into 16 groups
      according to antigenic relationships. It has been suggested that antigenic
      variants might arise in nature by immunologic pressure. To investigate this
      possibility, attempts were made to select variants by cloning 16 different plaque
      purified RV serotypes in the presence of homologous, polyclonal antisera.
      Isolates were examined for evidence of variation in serum cross-neutralization
      tests using parental antisera and, in some cases, antisera prepared for the
      isolates. Only RV type 17 (RV-17) yielded major antigenic variants after cloning.
      With some variants, as much as a 500-fold difference in neutralizing titer was
      obtained with the parental antiserum. By using antisera for two of the variants,
      it was determined that they are prime strains of the parental RV-17. Continuing
      attempts at immunoselection by using antisera for one of these prime strains
      yielded additional antigenic variants. By using antisera prepared for three of
      these new variants, it was determined that one of them is a prime strain of the
      virus from which it was derived. Cross-neutralization tests with the two
      remaining isolates indicate that, according to conventional practice, they no
      longer would be classified as RV-17.

PMID- 8995662
TI  - Specificity and affinity of binding of herpes simplex virus type 2 glycoprotein B
      to glycosaminoglycans.
AB  - Herpes simplex virus type 2 (HSV-2) interacts with cell surface
      glycosaminoglycans during virus attachment. Glycoprotein B of HSV-2 can
      potentially mediate the interaction between the virion and cell surface
      glycosaminoglycans. To determine the specificity, kinetics, and affinity of these
      interactions, we used plasmon resonance-based biosensor technology to measure HSV
      2 glycoprotein binding to glycosaminoglycans in real time. The recombinant
      soluble ectodomain of HSV-2 gB (gB2) but not the soluble ectodomain of HSV-2 gD
      bound readily to biosensor surfaces coated with heparin. The affinity constants
      (Kds) were determined for gB2 (Kd = 7.7 x 10(-7) M) and for gB2 deltaTM (Kd = 9.9
      x 10(-7) M), a recombinant soluble form of HSV-2 gB in which only its
      transmembrane domain has been deleted. gB2 binding to the heparin surface was
      competitively inhibited by low concentrations of heparin (50% effective dose
      [ED50] = 0.08 microg/ml). Heparan sulfate and dermatan sulfate glycosaminoglycans
      have each been suggested as cell surface receptors for HSV. Our biosensor
      analyses showed that both heparan sulfate and dermatan sulfate inhibited gB2
      binding (ED50 = 1 to 5 microg/ml), indicating that gB2 interacts with both
      heparin-like and dermatan sulfate glycosaminoglycans. Chondroitin sulfate A, in
      contrast, inhibited gB2 binding to heparin only at high levels (ED50 = 65
      microg/ml). The affinity and specificity of gB2 binding to glycosaminoglycans
      demonstrated in these studies support its role in the initial binding of HSV-2 to
      cells bearing heparan sulfate or dermatan sulfate glycosaminoglycans.

PMID- 8995663
TI  - The influenza A virus PB2 polymerase subunit is required for the replication of
      viral RNA.
AB  - The transcription and replication of influenza virus RNA (vRNA) were
      reconstituted in vivo. The experimental approach involved the transfection of
      plasmids encoding the viral subunits of the polymerase and the nucleoprotein into
      cells infected with a vaccinia virus recombinant virus expressing the T7 RNA
      polymerase. As templates, one of two model RNAs was transfected: vNSZ or cNSZ
      RNA. The RNAs were 240 nucleotides in length, contained the terminal sequences of
      the NS viral segment, and were of negative or positive polarity, respectively.
      The accumulation of cRNA and mRNA in cells transfected with vNSZ RNA and the
      accumulation of vRNA and mRNA in cells transfected with cNSZ RNA were determined
      by RNase protection assays with labeled vNSZ-L or cNSZ-L probes. The patterns of
      protected bands obtained indicated that both cRNA replication intermediate and
      mRNA accumulated when the system was reconstituted with vNSZ RNA. Likewise, both
      vRNA and mRNA accumulated after reconstitution with cNSZ RNA. The reconstitution
      of incomplete systems in which any of the subunits of the polymerase or the model
      RNA were omitted was completely negative for the accumulation of cRNA or vRNA,
      indicating that the presence of the PB2 subunit in the polymerase is required for
      replication of vRNA.

PMID- 8995664
TI  - S-phase-dependent cell cycle disturbances caused by Aleutian mink disease
      parvovirus.
AB  - We examined replication of the autonomous parvovirus Aleutian mink disease
      parvovirus (ADV) in relation to cell cycle progression of permissive Crandell
      feline kidney (CRFK) cells. Flow cytometric analysis showed that ADV caused a
      composite, binary pattern of cell cycle arrest. ADV-induced cell cycle arrest
      occurred exclusively in cells containing de novo-synthesized viral nonstructural
      (NS) proteins. Production of ADV NS proteins, indicative of ADV replication, was
      triggered during S-phase traverse. The NS+ cells that were generated during later
      parts of S phase did not undergo cytokinesis and formed a distinct population,
      termed population A. Formation of population A was not prevented by VM-26,
      indicating that these cells were arrested in late S or G2 phase. Cells in
      population A continued to support high-level ADV DNA replication and production
      of infectious virus after the normal S phase had ceased. A second, postmitotic,
      NS+ population (termed population B) arose in G0/G1, downstream of population A.
      Population B cells were unable to traverse S phase but did exhibit low-level DNA
      synthesis. Since the nature of this DNA synthesis was not examined, we cannot at
      present differentiate between G1 and early S arrest in population B. Cells that
      became NS+ during S phase entered population A, whereas population B cells
      apparently remained NS- during S phase and expressed high NS levels postmitosis
      in G0/G1. This suggested that population B resulted from leakage of cells with
      subthreshold levels of ADV products through the late S/G2 block and,
      consequently, that the binary pattern of ADV-induced cell cycle arrest may be
      governed merely by viral replication levels within a single S phase. Flow
      cytometric analysis of propidium iodide fluorescence and bromodeoxyuridine uptake
      showed that population A cells sustained significantly higher levels of DNA
      replication than population B cells during the ADV-induced cell cycle arrest.
      Therefore, the type of ADV-induced cell cycle arrest was not trivial and could
      have implications for subsequent viral replication in the target cell.

PMID- 8995665
TI  - High-efficiency transduction of human lymphoid progenitor cells and expression in
      differentiated T cells.
AB  - Gene therapy strategies for humans have been limited by low transduction
      efficiencies and poor expression of retroviral vectors in differentiated progeny
      cells carrying the transduced vector. Here we describe a strategy utilizing a
      cell surface reporter gene, murine thy-1.2, selectable by fluorescence-activated
      cell sorting (FACS), to achieve higher gene marking efficiencies. Human CD34
      positive cells were transduced by a murine retroviral vector bearing the thy-1.2
      marker and pseudotyped with vesicular stomatitis virus G protein, followed by
      FACS to enrich for CD34-positive cells that express Thy-1.2 on the cell surface.
      Gene marking and expression after differentiation into thymocytes were assessed
      in a SCID-hu Thy/Liv mouse model for human lymphoid progenitor cell gene therapy.
      We found that virtually all of the differentiated T-cell progeny were marked with
      vector sequences. It is of particular importance that reconstitution with the
      selected cells resulted in expression of Thy-1.2 in up to 71% of donor-derived
      thymocytes. It is of note that the donor-derived thymocytes that did not express
      Thy-1.2 still harbored vector thy-1.2 sequences, suggesting repression of
      transgene expression in some cells during progenitor cell differentiation into
      thymocytes. These studies provide a proof of concept for efficient expression of
      transgenes through T-lymphoid differentiation and a potential basis for utilizing
      similar strategies in human gene therapy clinical trials.

PMID- 8995666
TI  - A novel cellular site-specific DNA-binding protein cooperates with the viral NS1
      polypeptide to initiate parvovirus DNA replication.
AB  - Replication of linear single-stranded parvovirus DNA proceeds by a rolling
      hairpin mechanism which generates long, palindromic, duplex concatamers.
      Processing to monomer length requires initiation from origins of DNA replication
      located at the 3' and 5' ends of each embedded monomer, reactions which can be
      recapitulated in vitro for minute virus of mice (MVM). To determine which
      cellular proteins were essential for replication from these origins, S100
      extracts from 293S cells were fractionated on phosphocellulose. When recombined,
      these fractions were able to support replication in vitro, dependent on the viral
      initiator protein NS1, using plasmid forms of the 5' origin or the minimal 3'
      origin as templates. Fraction P-cell 1 contains two factors, replication protein
      A (RPA) and proliferating-cell nuclear antigen (PCNA), known to be essential for
      simian virus 40 replication in vitro. When P-cell 1 was replaced with purified
      recombinant RPA and PCNA, NS1-mediated MVM replication initiated from the 5'
      origin but not from the 3' origin. The 3' origin is a 50-bp sequence containing
      three distinct recognition elements, an NS1 binding site, a site at which NS1
      nicks the DNA to generate the priming 3' OH, and a region containing a consensus
      activated transcription factor (ATF) binding site. To identify the missing
      factor(s) for 3' origin replication, P-cell 1 was fractionated by further
      chromatography and active fractions were identified by their ability to
      complement RPA, PCNA, and P-cell 2 for NS1-mediated, origin-specific replication.
      Gel shift and UV cross-linking analysis of the replication-competent fractions
      revealed a novel 110-kDa sequence-specific DNA binding protein which recognized
      the consensus ATF binding site region of the origin and which we have termed
      parvovirus initiation factor, or PIF. Binding of PIF appears to activate the
      endonuclease function of NS1, allowing efficient and specific nicking of the 3'
      minimal origin under stringent conditions in vitro.

PMID- 8995667
TI  - Chimeric Sindbis viruses dependent on the NS3 protease of hepatitis C virus.
AB  - The hepatitis C virus (HCV) NS3 protease cleaves the viral polyprotein at
      specific sites to release the putative components of the HCV replication
      machinery. Selective inhibition of this enzyme is predicted to block virus
      replication, and NS3 is thus considered an attractive candidate for development
      of anti-HCV therapeutics. To set up a system for analysis of NS3 protease
      activity in cultured cells, we constructed a family of chimeric Sindbis viruses
      which carry sequences coding for NS3 and its activator, NS4A, in their genomes.
      HCV sequences were fused to the gene coding for the Sindbis virus structural
      polyprotein via an NS3-specific cleavage site, with the expectation that
      processing of the chimeric polyprotein, nucleocapsid assembly, and generation of
      viable viral particles would occur only upon NS3-dependent proteolysis. Indeed,
      the chimeric genomes encoding an active NS3 protease produced infectious viruses
      in mammalian cells, while those encoding NS3 inactivated by alanine substitution
      of the catalytic serine did not. However, in infected cells chimeric genomes
      recombined, splicing out HCV sequences and reverting to pseudo-wild-type Sindbis
      virus. To force retention of HCV sequences, we modified one of the initial
      chimeras by introducing a second NS3 cleavage site in the Sindbis virus portion
      of the recombinant polyprotein, anticipating that revertants not encoding an
      active NS3 protease would not be viable. The resulting chimera produced
      infectious viruses which replicated at a lower rate than the parental construct
      and displayed a marked temperature dependence in the formation of lysis plaques
      yet stably expressed NS3.

PMID- 8995669
TI  - The N terminus of hamster polyomavirus middle T antigen carries a determinant for
      specific activation of p59c-Fyn.
AB  - Transformation by rodent polyomaviruses is mediated primarily by middle T
      antigen, a membrane-bound protein that does not carry an intrinsic enzymatic
      activity but interacts and subverts the activity of cellular regulators of
      proliferation. The multiple protein partners of murine polyomavirus (Py) middle T
      antigen include the tyrosine kinases c-Src and, to a lesser extent, c-Fyn and c
      Yes. By contrast, the hamster polyomavirus (HaPV) middle T antigen selectively
      activates the c-Fyn gene product. This difference may account for the contrasting
      tumor patterns induced by the two viruses. The sequences of the respective N
      terminal and C-terminal functional domains of murine Py and HaPV middle T
      antigens are highly conserved whereas the intervening stretches are clearly
      divergent, leading to the speculation that this divergence may direct the
      specificity for tyrosine kinase activation. We have addressed this issue by
      constructing a chimera middle T antigen molecule carrying the N-terminal domain
      from HaPV (exon 1) in phase with the other two domains from murine Py (exon 2).
      The biological properties of this chimera molecule are indistinguishable from
      those of HaPV middle T antigen; it specifically activates p59c-Fyn and carries
      the transforming phenotype of the HaPV middle T antigen on rat fibroblasts.

PMID- 8995668
TI  - Encapsidation of turnip crinkle virus is defined by a specific packaging signal
      and RNA size.
AB  - A protoplast infection assay has been used to reliably examine the viral RNA
      encapsidation of turnip crinkle virus (TCV). Analysis of the encapsidation of
      various mutant viral RNAs revealed that a 186-nucleotide (nt) region at the 3'
      end of the coat protein (CP) gene, with a bulged hairpin loop of 28 nt as its
      most essential element, was indispensable for TCV RNA encapsidation. When RNA
      fragments containing the 186-nt region were used to replace the CP gene of a
      different virus, tomato bushy stunt virus, the resulting chimeric viral RNAs were
      encapsidated into TCV virions. Furthermore, analysis of the encapsidated chimeric
      RNA species established that the RNA size was an important determinant of the TCV
      assembly process.

PMID- 8995670
TI  - Mutations in the matrix protein of human immunodeficiency virus type 1 inhibit
      surface expression and virion incorporation of viral envelope glycoproteins in
      CD4+ T lymphocytes.
AB  - Highly conserved amino acids in the second helix structure of the human
      immunodeficiency virus type 1 (HIV-1) MA protein were identified to be critical
      for the incorporation of viral Env proteins into HIV-1 virions from transfected
      COS-7 cells. The effects of these MA mutations on viral replication in the HIV-1
      natural target cells, CD4+ T lymphocytes, were evaluated by using a newly
      developed system. In CD4+ T lymphocytes, mutations in the MA domain of HIV-1 Gag
      also inhibited the incorporation of viral Env proteins into mature HIV-1 virions.
      Furthermore, mutations in the MA domain of HIV-1 Gag reduced surface expression
      of viral Env proteins in CD4+ T lymphocytes. The synthesis of gp160 and cleavage
      of gp160 to gp120 were not significantly affected by MA mutations. On the other
      hand, the stability of gp120 in MA mutant-infected cells was significantly
      reduced compared to that in the parental wild-type virus-infected cells. These
      results suggest that functional interaction between HIV-1 Gag and Env proteins is
      not only critical for efficient incorporation of Env proteins into mature virions
      but also important for proper intracellular transport and stable surface
      expression of viral Env proteins in infected CD4+ T lymphocytes. A single amino
      acid substitution in MA abolished virus infectivity in dividing CD4+ T
      lymphocytes without significantly affecting virus assembly, virus release, or
      incorporation of Gag-Pol and Env proteins, suggesting that in addition to its
      functional role in virus assembly, the MA protein of HIV-1 also plays an
      important role in other steps of virus replication.

PMID- 8995671
TI  - The CD4-independent tropism of human immunodeficiency virus type 2 involves
      several regions of the envelope protein and correlates with a reduced activation
      threshold for envelope-mediated fusion.
AB  - Several human immunodeficiency virus type 2 (HIV-2) strains have been shown to
      infect some CD4-negative cell lines (P. R. Clapham, A. McKnight, and R. A. Weiss,
      J. Virol. 66:3531-3537, 1992). Using molecular clones of HIV-2 with a CD4
      independent tropism, we have identified critical amino acid residues in the
      envelope protein which are required for CD4-independent infection. Mutations
      located immediately upstream of a proposed coiled coil domain in the
      transmembrane protein (A526T or I528M) and flanking the base of the V4 loop
      (L378F and K403R) are crucial for the CD4-independent phenotype. Of several
      mutations conferring a positive charge in V1, V2, and V3, only the change in V3
      (Q310K) helped to enhance the CD4-independent phenotype but could not mediate it
      on its own. These mutations reduce the amount of soluble CD4 required to trigger
      CD4-independent cell-cell fusion, suggesting that they lower the activation
      threshold for the fusion process. After binding to cell surface-anchored CD4, a
      CD4-independent recombinant envelope protein showed an increased binding of anti
      envelope protein antibodies, suggesting either an enhanced binding to cell
      surfaces or more extensive conformational changes in CD4-independent compared to
      CD4-dependent envelope proteins. The reduced activation threshold of CD4
      independent envelope proteins may thus enable them to utilize a membrane molecule
      for entry which is not as efficient as CD4 in triggering the conformational
      changes required for the membrane fusion process. CD4-independent HIV-2 variants
      may be conceptually similar to influenza virus variants capable of fusing at a
      higher than normal pH (R. S. Daniels, J. C. Downie, J. A. Hay, M. Knossow, J. J.
      Skehel, M. L. Wang, and D. C. Wiley, Cell 40:431-439, 1985).

PMID- 8995672
TI  - Initiation of vesicular stomatitis virus mutant polR1 transcription internally at
      the N gene in vitro.
AB  - The vesicular stomatitis virus (VSV) polymerase is thought to initiate
      transcription of its genome by first copying a small leader RNA complementary to
      the 3' end of the template. The polR VSV mutants, in contrast to wild-type virus,
      frequently read through the leader termination site during transcription in
      vitro. To shed light on polymerase termination and reinitiation events at the
      crucial leader-N gene junction, we employed RNase protection assays to precisely
      measure molar ratios of leader, N, and readthrough transcript accumulation in
      vitro. Wild-type virus synthesized essentially equimolar amounts of leader and N
      transcripts, but, unexpectedly, the polR1 mutant yielded about twice as much N
      mRNA as leader (ratio of 1.9 +/- 0.1). Primer extension assays ruled out an
      increase in abortive N transcript synthesis for polR1. Transcription entailed
      multiple rounds of synthesis, with transcript ratios remaining the same after 0.5
      or 2 h of synthesis, ruling out a significant contribution from polymerases "pre
      positioned" at the N gene. No significant degradation of either leader or N
      transcripts was observed after incubating purified products with virions. Our
      data lead us to conclude that transcription can initiate internally at the N
      gene, at least in the case of polR1 VSV. We propose, however, that productive
      internal initiation of transcription is a fundamental property of the VSV
      polymerase and that of related viruses. A model postulating two distinct
      polymerase complexes, one for leader synthesis and one for internal initiation,
      is presented.

PMID- 8995673
TI  - Role of CD4 epitopes outside the gp120-binding site during entry of human
      immunodeficiency virus type 1.
AB  - CD4 is the primary receptor for human immunodeficiency virus (HIV). The binding
      site for the surface glycoprotein of HIV type 1 (HIV-1), gp120, has been mapped
      to the C'-C" region of domain 1 of CD4. Previously, we have shown that a mutant
      of rat CD4, in which this region was exchanged for that of human CD4, is able to
      mediate infection of human cells by HIV-1, suggesting that essential interactions
      between HIV and CD4 are confined to this region. Our observations appeared to
      conflict with mutagenesis and antibody studies which implicate regions of CD4
      outside the gp120-binding site in postbinding events during viral entry. In order
      to resolve this issue, we have utilized a panel of anti-rat CD4 monoclonal
      antibodies in conjunction with the rat-human chimeric CD4 to distinguish sequence
      specific from steric effects. We find that several antibodies to rat CD4 inhibit
      HIV infection in cells expressing the chimeric CD4 and that this is probably due
      to steric hinderance. In addition, we demonstrate that replacement of the rat
      CDR3-like region with its human homolog does not increase the affinity of the rat
      human chimeric CD4 for gp120 or affect the exposure of gp41 following binding to
      CD4, providing further evidence that this region does not play a crucial role
      during entry of virus.

PMID- 8995674
TI  - Characterization of the human cytomegalovirus irs1 and trs1 genes: a second
      immediate-early transcription unit within irs1 whose product antagonizes
      transcriptional activation.
AB  - We have characterized the irs1 and trs1 genes of human cytomegalovirus. The
      previously identified mRNAs as well as their corresponding protein products pIRS1
      and pTRS1 could be detected during all phases of the viral replication cycle. The
      proteins were present in the nucleus and cytoplasm during the immediate-early and
      early phases of the viral growth cycle but were predominantly cytoplasmic late
      after infection. Although pIRS1 and pTRS1 exhibited little transcriptional
      activation potential on their own, both cooperated with the IE1 and IE2 proteins
      to enhance expression from a variety of viral promoters. We have also identified
      a previously undescribed immediate-early gene product encoded within the irs1
      gene that we have termed pIRS1(263). This new protein is encoded within the 3'
      end of the irs1 gene and is in the same reading frame as the large pIRS1 protein.
      Expression of the irs1(263) gene is controlled by a promoter that resides within
      the irs1 open reading frame in the unique short region of the viral genome.
      pIRS1(263) resides in the nucleus and antagonizes transcriptional activation by
      cytomegalovirus immediate-early proteins. We propose that pIRS1(263), whose
      promoter responds to immediate-early transcriptional activators, serves as part
      of a regulatory loop, antagonizing the function of the viral proteins that are
      responsible for its synthesis.

PMID- 8995675
TI  - Subgenomic replicons of the flavivirus Kunjin: construction and applications.
AB  - Several Kunjin virus (KUN) subgenomic replicons containing large deletions in the
      structural region (C-prM-E) and in the 3' untranslated region (3'UTR) of the
      genome have been constructed. Replicon RNA deltaME with 1,987 nucleotides deleted
      (from nucleotide 417 [in codon 108] in the C gene to nucleotide 2403 near the
      carboxy terminus of the E gene, inclusive) and replicon RNA C20rep with 2,247
      nucleotides deleted (from nucleotide 157 [in codon 20] in C to nucleotide 2403)
      replicated efficiently in electroporated BHK21 cells. A further deletion from
      C20rep of 53 nucleotides, reducing the coding sequence in core protein to two
      codons (C2rep RNA), resulted in abolishment of RNA replication. Replicon
      deltaME/76 with a deletion of 76 nucleotides in the 3'UTR of deltaME RNA
      (nucleotides 10423 to 10498) replicated efficiently, whereas replicon deltaME/352
      with a larger deletion of 352 nucleotides (nucleotides 10423 to 10774), including
      two conserved sequences RCS3 and CS3, was significantly inhibited in RNA
      replication. To explore the possibility of using a reporter gene assay to monitor
      synthesis of the positive strand and the negative strand of KUN RNA, we inserted
      a chloramphenicol acetyltransferase (CAT) gene into the 3'UTR of deltaME/76 RNA
      under control of the internal ribosomal entry site (IRES) of
      encephalomyelocarditis virus RNA in both plus (deltaME/76CAT[+])- and minus
      (deltaME/76CAT[-])-sense orientations. Although insertion of the IRES-CAT
      cassette in the plus-sense orientation resulted in a significant (10- to 20-fold)
      reduction of RNA replication compared to that of the parental deltaME/76 RNA, CAT
      expression was readily detected in electroporated BHK cells. No CAT expression
      was detected after electroporation of RNA containing the IRES-CAT cassette
      inserted in the minus-sense orientation despite its apparently more efficient
      replication (similar to that of deltaME/76 RNA); this result indicated that KUN
      negative-strand RNA was probably not released from its template after synthesis.
      Replacement of the CAT gene in the deltaME/76CAT(+) RNA with the neomycin gene
      (Neo) enabled selection and recovery of a BHK cell culture in which the majority
      of cells were continuously expressing the replicon RNA for 41 days (nine
      passages) without apparent cytopathic effect. The constructed KUN replicons
      should provide valuable tools to study flavivirus RNA replication as well as
      providing possible vectors for a long-lasting and noncytopathic RNA virus
      expression system.

PMID- 8995676
TI  - Canine distemper virus (CDV) infection of ferrets as a model for testing
      Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect
      against symptomatic infection.
AB  - Canine distemper virus (CDV) infection of ferrets causes an acute systemic
      disease involving multiple organ systems, including the respiratory tract,
      lymphoid system, and central nervous system (CNS). We have tested candidate CDV
      vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the
      highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of
      canarypox virus, which does not productively replicate in mammalian hosts.
      Juvenile ferrets were vaccinated twice with these constructs, or with an
      attenuated live-virus vaccine, while controls received saline or the NYVAC and
      ALVAC vectors expressing rabies virus glycoprotein. Control animals did not
      develop neutralizing antibody and succumbed to distemper after developing fever,
      weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous
      rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear
      cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited
      neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none
      developed viremia. Both recombinant vaccines also protected against the
      development of symptomatic distemper. However, ferrets receiving the live-virus
      vaccine lost weight, became lymphocytopenic, and developed the erythematous rash
      typical of CDV. These data show that ferrets are an excellent model for
      evaluating the ability of CDV vaccines to protect against symptomatic infection.
      Because the pathogenesis and clinical course of CDV infection of ferrets is quite
      similar to that of other Morbillivirus infections, including measles, this model
      will be useful in testing new candidate Morbillivirus vaccines.

PMID- 8995677
TI  - In vivo study of genetically simplified bovine leukemia virus derivatives that
      lack tax and rex.
AB  - Genetically simplified derivatives of complex retroviruses that replicate in
      animal models are useful tools to study the role of the complex regulatory genes
      in virus infection and pathogenesis and were proposed as a novel approach toward
      the development of vaccines against complex retroviruses. Previously we developed
      genetically simple derivatives of bovine leukemia virus (BLV) that can replicate
      in tissue culture independently of the BLV regulatory proteins, Tax and Rex, and
      the RIII and GIV open reading frames (K. Boris-Lawrie and H. M. Temin, J. Virol.
      69:1920-1924, 1995). These derivatives are encoded on novel, hybrid retrovirus
      genomes that contain transcriptional control sequences of a simple retrovirus and
      gag-pol or env genes of the complex BLV. The first-generation simple BLV
      derivatives replicate as complementary viruses (coviruses) by using separate gag
      pol or env genomes, and therefore virus spread is limited to cells that are
      infected with both covirus genomes. Here we describe a second-generation simple
      BLV derivative that is encoded on a single hybrid genome. We show the virus to be
      replication competent by successive passage on D17 target cells and by analysis
      of viral RNA and proteins in the infected cells. Furthermore, we evaluate the
      immunogenicity and infectivity of the simple BLV derivatives in a BLV animal
      model. Small groups of rats were injected either with virus-producing cells or
      with proviral DNA. Western immunoblot analysis revealed that antibodies against
      the major viral antigenic determinants are induced in response to either method
      of introduction and that seroconversion is sustained in most of the rats for at
      least 6 months (the duration of the study). The magnitudes of the antiviral
      responses were similar in rats infected with the first-generation simple BLV
      coviruses, the second-generation replication-competent derivative, or wild-type
      BLV. Wild-type BLV typically infects peripheral blood mononuclear cells (PBMC),
      and the simple BLV derivatives were also found to infect PBMC as demonstrated by
      PCR amplification of proviral sequences and reverse transcriptase PCR
      amplification of viral RNA in treated rats. These results establish that simple
      BLV derivatives lacking tax and rex are infectious and immunogenic in rats. These
      viruses will be useful tools in comparative studies with BLV to evaluate the role
      of tax and rex in maintenance of virus load and in disease outcome.

PMID- 8995678
TI  - Identification and characterization of a G protein-coupled receptor homolog
      encoded by murine cytomegalovirus.
AB  - This report describes the identification of a murine cytomegalovirus (MCMV) G
      protein-coupled receptor (GCR) homolog. This open reading frame (M33) is most
      closely related to, and collinear with, human cytomegalovirus UL33, and homologs
      are also present in human herpesvirus 6 and 7 (U12 for both viruses). Conserved
      counterparts in the sequenced alpha- or gammaherpesviruses have not been
      identified to date, suggesting that these genes encode proteins which are
      important for the biological characteristics of betaherpesviruses. We have
      detected transcripts for both UL33 and M33 as early as 3 or 4 h postinfection,
      and these reappear at late times. In addition, we have identified N-terminal
      splicing for both the UL33 and M33 RNA transcripts. For both open reading frames,
      splicing results in the introduction of amino acids which are highly conserved
      among known GCRs. To characterise the function of the M33 in the natural host,
      two independent MCMV recombinant viruses were prepared, each of which possesses
      an M33 open reading frame which has been disrupted with the beta-galactosidase
      gene. While the recombinant M33 null viruses showed no phenotypic differences in
      replication from wild-type MCMV in primary mouse embryo fibroblasts in vitro,
      they showed severely restricted growth in the salivary glands of infected mice.
      These data suggest that M33 plays an important role in vivo, in particular in the
      dissemination to or replication in the salivary gland, and provide the first
      evidence for the function of a viral GCR homolog in vivo.

PMID- 8995679
TI  - Role of early and late replication events in induction of apoptosis by
      baculoviruses.
AB  - Autographa californica nuclear polyhedrosis virus (AcMNPV) mutants that lack the
      apoptotic suppressor gene p35 cause apoptosis in Spodoptera frugiperda SF21
      cells. To identify a viral signal(s) that induces programmed cell death, we first
      defined the timing of apoptotic events during infection. Activation of a P35
      inhibitable caspase, intracellular fragmentation of host and AcMNPV DNA, and cell
      membrane blebbing coincided with the initiation of viral DNA synthesis between 9
      and 12 h after infection and thus suggested that apoptotic signaling begins at or
      before this time. Virus entry was required since binding of budded virus to host
      cell receptors alone was insufficient to induce apoptosis. To therefore determine
      the contribution of early and late replication events to apoptotic signaling, we
      used the AcMNPV mutant ts8 with a temperature-sensitive lesion in the putative
      helicase gene p143. At the nonpermissive temperature at which viral DNA synthesis
      was conditionally blocked, ts8 caused extensive apoptosis of the SF21 cell line
      p3576D, which dominantly interferes with anti-apoptotic function of viral P35.
      Confirming that apoptosis can be induced in the absence of normal viral DNA
      synthesis, parental SF21 cells also underwent apoptosis when infected with a ts8
      p35 deletion mutant at the nonpermissive temperature. However, maximum levels of
      ts8 p35 deletion mutant-induced apoptosis required a temperature-sensitive
      event(s) that included the initiation of viral DNA synthesis. Collectively, these
      data suggested that baculovirus-induced apoptosis can be triggered by distinct
      early (pre-DNA synthesis) and late replicative events, including viral DNA
      synthesis or late gene expression.

PMID- 8995680
TI  - The barley stripe mosaic virus 58-kilodalton beta(b) protein is a multifunctional
      RNA binding protein.
AB  - The barley stripe mosaic virus (BSMV) beta(b) gene product is the major viral
      nonstructural protein synthesized during early stages of the infection cycle and
      is required for systemic movement of the virus. To examine the biochemical
      properties of beta(b), a histidine tag was engineered at the amino terminus and
      the protein was purified from BSMV-infected barley tissue by metal affinity
      chromatography. The beta(b) protein bound ATPs in vitro, with a preference for
      ATP over dATP, and also exhibited ATPase activity. In addition, beta(b) bound RNA
      without detectable sequence specificity. However, binding was selective, as the
      beta(b) protein had a strong affinity for both single-stranded (ss) and double
      stranded (ds) RNAs but not for tRNA or DNA substrates. Mutational analyses of
      beta(b) purified from Escherichia coli indicated that the protein has multiple
      RNA binding sites. These sites appear to contribute differently, because mutants
      that were altered in their binding affinities for ss and ds RNA substrates were
      recovered.

PMID- 8995681
TI  - Physical and functional interactions between herpes simplex virus immediate-early
      proteins ICP4 and ICP27.
AB  - The ordered expression of herpes simplex virus type 1 (HSV-1) genes, during the
      course of a productive infection, requires the action of the virus immediate
      early regulatory proteins. Using a protein interaction assay, we demonstrate
      specific in vitro protein-protein interactions between ICP4 and ICP27, two
      immediate-early proteins of HSV-1 that are essential for virus replication. We
      map multiple points of contact between these proteins. Furthermore, by
      coimmunoprecipitation experiments, we demonstrate the following. (i) ICP4-ICP27
      complexes are present in extracts from HSV-1 infected cells. (ii) ICP27 binds
      preferentially to less modified forms of ICP4, a protein that is extensively
      modified posttranslationally. We also demonstrate, by performing electrophoretic
      mobility shift assays and supershifts with monoclonal antibodies to ICP4 or
      ICP27, that both proteins are present in a DNA-protein complex with a
      noncanonical ICP4 binding site present in the HSV thymidine kinase (TK) gene.
      ICP4, in extracts from cells infected with ICP27-deficient viruses, is impaired
      in its ability to form complexes with the TK site but not with the canonical site
      from the alpha4 gene. However, ICP4 is able to form complexes with the TK probe,
      in the absence of ICP27, when overproduced in mammalian cells or expressed in
      bacteria. These data suggest that the inability of ICP4 from infected cell
      extracts to bind the TK probe in the absence of ICP27 does not reflect a
      requirement for the physical presence of ICP27 in the complex. Rather, they imply
      that ICP27 is likely to modulate the DNA binding activity of ICP4 by affecting
      its posttranslational modification status. Therefore, we propose that ICP27, in
      addition to its established role as a posttranscriptional regulator of virus gene
      expression, may also modulate transcription either through direct or indirect
      interactions with HSV regulatory regions, or through its ability to modulate the
      DNA binding activity of ICP4.

PMID- 8995682
TI  - Role of glycoprotein PE2 in formation and maturation of the Sindbis virus spike.
AB  - Sindbis virus envelope assembly is a multistep process resulting in the
      maturation of a rigid, highly ordered T=4 icosahedral protein lattice containing
      80 spikes composed of trimers of E1-E2 heterodimers. Intramolecular disulfide
      bonds within E1 stabilize E1-E1 associations required for envelope formation and
      maintenance of the envelope's structural integrity. The structural integrity of
      the envelope protein lattice is resistant to reduction by dithiothreitol (DTT),
      indicating that E1 disulfides which stabilize structural domains become
      inaccessible to DTT at some point during virus maturation. The development of E1
      resistance to DTT occurs prior to the completion of E1 folding and is temporally
      correlated with spike assembly in the endoplasmic reticulum. From these data we
      have predicted that in the final stages of spike assembly, E1 intramolecular
      disulfides, which stabilize the structural integrity of the envelope protein
      lattice, are buried within the spike and become inaccessible to the reductive
      activity of DTT. The spike is formed prior to the completion of E1 folding, and
      we have suggested that PE2 (the precursor to E2) may play a critical role in E1
      folding after PE2-E1 oligomer formation has occurred. In this study we have
      investigated the role of PE2 in E1 folding, oligomer formation, and development
      of E1 resistance to both protease digestion and reduction by DTT by using a
      Sindbis virus replicon (SINrep/E1) which allows for the expression of E1 in the
      presence of truncated PE2. Through pulse-chase analysis of both Sindbis virus-
      and SINrep/E1-infected cells, we have determined that the folding of E1 into a
      trypsin-resistant conformation and into its most compact and stable form is not
      dependent upon association of E1 with PE2. However, E1 association with PE2 is
      required for oligomer formation, the export of E1 from the endoplasmic reticulum,
      and E1 acquisition of resistance to DTT.

PMID- 8995683
TI  - Multiple widely spaced elements determine the efficiency with which a distal
      cistron is expressed from the polycistronic pregenomic RNA of figwort mosaic
      caulimovirus.
AB  - The polycistronic expression mechanism of the plant pararetrovirus figwort mosaic
      caulimovirus (FMV) depends upon cis-acting elements present in its pregenomic RNA
      and a trans-acting protein (P6) which is expressed from a monocistronic
      subgenomic RNA. Using transient expression of FMV-derived polycistronic reporter
      constructs in Nicotiana edwardsonii cell suspension protoplasts, we further
      analyzed the cis-acting elements involved in polycistronic expression. A cis
      acting element located within the first 74 nucleotides of the 7,954-nucleotide
      pregenomic RNA appears to be essential for P6 to transactivate expression of an
      internal cistron. Expression of this internal cistron, in the presence of P6, is
      greatly enhanced by the combined presence of two cis-acting elements located at
      the 3' end of the polycistronic RNA. Surprisingly, deletion of the most upstream
      of these two 3' cis-acting elements exposed a negative-acting element located
      internally on the polycistronic RNA, at the 3' end of open reading frame I. The
      action of both this negative-acting internal element and the positive-acting 3'
      elements is more pronounced when the large 5' untranslated leader region is
      present. This indicates that the 5' untranslated leader region is central to
      regulation of the FMV gene expression mechanism. Although a limited set of
      elements suffices to direct polycistronic expression in this eukaryotic system, a
      complex interplay between elements is involved in the spatial regulation of the
      genes present on the pregenomic RNA of FMV.

PMID- 8995684
TI  - Interaction of an adenovirus 14.7-kilodalton protein inhibitor of tumor necrosis
      factor alpha cytolysis with a new member of the GTPase superfamily of signal
      transducers.
AB  - The adenovirus (Ad) 14.7-kDa E3 protein (E3-14.7K), which can inhibit tumor
      necrosis factor alpha (TNF-alpha) cytolysis, was used to screen HeLa cell cDNA
      libraries for interacting proteins in the yeast two-hybrid system. A new member
      of the low-molecular-weight (LMW) GTP-binding protein family with Ras and ADP
      ribosylation factor homology was discovered by this selection and has been named
      FIP-1 (14.7K-interacting protein). FIP-1 colocalized with Ad E3-14.7K in the
      cytoplasm especially near the nuclear membrane and in discrete foci on or near
      the plasma membrane. Its interaction with E3-14.7K was dependent on the FIP-1 GTP
      binding domain. The stable expression of FIP-1 antisense message partially
      protected the cells from TNF-alpha cytolysis. FIP-1 was associated transiently
      with several unknown phosphorylated cellular proteins within 15 min after
      treatment with TNF-alpha. FIP-1 mRNA was expressed ubiquitously but at higher
      levels in human skeletal muscle, heart, and brain. In addition to homology to
      other LMW GTP-binding proteins, FIP-1 has regions of homology to two prokaryotic
      metalloproteases. However, there was no homology between FIP-1 and any of the
      recently isolated death proteins in the TNF-alpha or Fas/APO1 cytolytic pathway
      and no interaction with several members of the Bcl-2 family of inhibitors of
      apoptosis. These data suggest that FIP-1, as a cellular target for Ad E3-14.7K,
      is either a new intermediate on a previously described pathway or part of a novel
      TNF-alpha-induced cell death pathway. FIP-1 has two consensus sequences for
      myristoylation which would be expected to facilitate membrane association and
      also has sequences for Ser/Thr as well as Tyr phosphorylation that could affect
      its function.

PMID- 8995685
TI  - bcl-2 acts early to restrict Semliki Forest virus replication and delays virus
      induced programmed cell death.
AB  - As characterized by morphological assessment and terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling, Semliki Forest virus
      (SFV) infection of rat prostatic adenocarcinoma cells triggers an apoptotic cell
      response. Cell death proceeded more rapidly following infection with the
      neurovirulent L10 strain of SFV than with the avirulent A7 strain. Overexpression
      of the antiapoptotic proto-oncogene bcl-2 allowed survival of cultures infected
      with either strain of virus. bcl-2 overexpression drastically reduced the numbers
      of productively infected cells within the cultures. In situ hybridization for
      viral message-sense RNA coupled with immunostaining for viral protein indicated
      that bcl-2 functions at an early stage of the virus life cycle, at entry,
      pretranscriptional events or at transcription, to inhibit virus replication.
      Double-immunofluorescent labeling for bcl-2 and viral glycoproteins revealed
      double-positive cells, demonstrating that with time, this early block in
      replication can be overcome. These productively infected bcl-2-expressing cells
      do, with time, undergo apoptosis. As a result of changing the balance between
      cell death and cell division by restricting productive virus replication and
      delaying virus-induced cell death, bcl-2 expression led to the establishment of
      chronically infected cell lines which could be passaged.

PMID- 8995686
TI  - Human immunodeficiency virus type 1 gp120 stimulates cytomegalovirus replication
      in monocytes: possible role of endogenous interleukin-8.
AB  - Recombinant gp120, but not other human immunodeficiency type 1 (HIV-1) structural
      proteins, dose-dependently stimulates human cytomegalovirus (HCMV) immediate
      early antigen (IEA) expression and infectious virus yield in freshly isolated
      normal monocytes infected with HCMV. Monoclonal antibodies (MAbs) recognizing the
      gp120 V3 loop, as well as V3 loop octameric multibranched peptides and antibody
      to galactocerebroside, but not sCD4, abrogate the gp120 stimulation of IEA
      expression, suggesting that the effect involves V3 loop-galactocerebroside
      interaction and is not mediated by CD4. Interleukin 8 (IL-8) gene expression is
      enhanced in monocytes treated with gp120 at the level of both mRNA and released
      protein. Exogenous IL-8 could replace gp120 in the stimulation of HCMV infection,
      while a MAb capable of neutralizing IL-8 activity abrogates the gp120-induced
      HCMV stimulation. These data indicate that HIV-1 glycoprotein induces stimulation
      of productive infection of monocytes with HCMV and that such stimulation may be
      mediated by the upregulation of IL-8 gene expression. This is the first evidence
      that HIV-1 may affect HCMV replication indirectly, via the interaction of gp120
      with the monocyte membrane, in the complete absence of retroviral replication,
      through the stimulation of IL-8 release. Because in HIV-1-infected individuals,
      HCMV infection is frequently activated and the levels of circulating IL-8 are
      enhanced, these findings may be pathogenetically relevant.

PMID- 8995687
TI  - Functions of the tobacco etch virus RNA polymerase (NIb): subcellular transport
      and protein-protein interaction with VPg/proteinase (NIa).
AB  - The NIb protein of tobacco etch potyvirus (TEV) possesses several functions,
      including RNA-dependent RNA polymerase and nuclear translocation activities.
      Using a reporter protein fusion strategy, NIb was shown to contain two
      independent nuclear localization signals (NLS I and NLS II). NLS I was mapped to
      a sequence within amino acid residues 1 to 17, and NLS II was identified between
      residues 292 and 316. Clustered point mutations resulting in substitutions of
      basic residues within the NLSs were shown previously to disrupt nuclear
      translocation activity. These mutations also abolished TEV RNA amplification when
      introduced into the viral genome. The amplification defects caused by each NLS
      mutation were complemented in trans within transgenic cells expressing functional
      NIb, although the level of complementation detected for each mutant differed
      significantly. Combined with previous results (X. H. Li and J. C. Carrington,
      Proc. Natl. Acad. Sci. USA 92:457-461, 1995), these data suggest that the NLSs
      overlap with essential regions necessary for NIb trans-active function(s). The
      fact that NIb functions in trans implies that it must interact with one or more
      other components of the genome replication apparatus. A yeast two-hybrid system
      was used to investigate physical interactions between NIb and several other TEV
      replication proteins, including the multifunctional VPg/proteinase NIa and the
      RNA helicase CI. A specific interaction was detected between NIa and NIb.
      Deletion of any of five regions spanning the NIb sequence resulted in NIb
      variants that were unable to interact with NIa. Clustered point mutations
      affecting the conserved GDD motif or NLS II within the central region of NIb, but
      not mutations affecting NLS I near the N terminus, reduced or eliminated the
      interaction. The C-terminal proteinase (Pro) domain of NIa, but not the N
      terminal VPg domain, interacted with NIb. The effects of NIb mutations within NLS
      I, NLS II, and the GDD motif on the interaction between the Pro domain and NIb
      were identical to the effects of these mutations on the interaction between full
      length NIa and NIb. These data are compatible with a model in which NIb is
      directed to replication complexes through an interaction with the Pro domain of
      NIa.

PMID- 8995688
TI  - A molecularly cloned, pathogenic, neutralization-resistant simian
      immunodeficiency virus, SIVsmE543-3.
AB  - An infectious molecular clone of simian immunodeficiency virus SIVsm was derived
      from a biological isolate obtained late in disease from an immunodeficient rhesus
      macaque (E543) with SIV-induced encephalitis. The molecularly cloned virus,
      SIVsmE543-3, replicated well in macaque peripheral blood mononuclear cells and
      monocyte-derived macrophages and resisted neutralization by heterologous sera
      which broadly neutralized genetically diverse SIV variants in vitro. SIVsmE543-3
      was infectious and induced AIDS when inoculated intravenously into pig-tailed
      macaques (Macaca nemestrina). Two of four infected macaques developed no
      measurable SIV-specific antibody and succumbed to a wasting syndrome and SIV
      induced meningoencephalitis by 14 and 33 weeks postinfection. The other two
      macaques developed antibodies reactive in Western blot and virus neutralization
      assays. One macaque was sacrificed at 1 year postinoculation, and the survivor
      has evidence of immunodeficiency, characterized by persistently low CD4
      lymphocyte subsets in the peripheral blood. Plasma samples from these latter
      animals neutralized SIVsmE543-3 but with much lower efficiency than
      neutralization of other related SIV strains, confirming the difficulty by which
      this molecularly cloned virus is neutralized in vitro. SIVsmE543-3 will provide a
      valuable reagent for studying SIV-induced encephalitis, mapping determinants of
      neutralization, and determining the in vivo significance of resistance to
      neutralization in vitro.

PMID- 8995689
TI  - Persistent poliovirus infection in mouse motoneurons.
AB  - Poliovirus (PV) is the causal agent of paralytic poliomyelitis. Many survivors of
      the acute disease, after decades of clinical stability, develop new muscular
      symptoms called postpolio syndrome. It has been hypothesized that the persistence
      of PV in the spinal cord is involved in the etiology of this syndrome. To
      investigate the ability of PV to persist in the spinal cord after the onset of
      paralysis, we exploited a mouse model in which most animals inoculated with a
      mouse-adapted mutant survived after the onset of paralysis. Light microscopy and
      ultrastructural immunohistochemical studies and reverse transcription followed by
      nested PCR performed on spinal cord from paralyzed mice demonstrated that PV
      persisted in the mouse spinal cord for at least 12 months after the onset of
      paralysis. This mouse model provides a new tool for studying poliomyelitis
      evolution after the onset of paralysis.

PMID- 8995690
TI  - Human cytomegalovirus infection inhibits G1/S transition.
AB  - Cell cycle progression during cytomegalovirus infection was investigated by
      fluorescence-activated cell sorter (FACS) analysis of the DNA content in growth
      arrested as well as serum-stimulated human fibroblasts. Virus-infected cells
      maintained in either low (0.2%) or high (10%) serum failed to progress into S
      phase and failed to divide. DNA content analysis in the presence of G1/S
      (hydroxyurea and mimosine) and G2/M (nocodazole and colcemid) inhibitors
      demonstrated that upon virus infection of quiescent (G0) cells, the cell cycle
      did not progress beyond the G1/S border even after serum stimulation. Proteins
      which normally indicate G1/S transition (proliferating cell nuclear antigen
      [PCNA]) or G2/M transition (cyclin B1) were elevated by virus infection. PCNA
      levels were induced in infected cells and exhibited a punctate pattern of nuclear
      staining instead of the diffuse pattern observed in mock-infected cells. Cyclin
      B1 was induced in infected cells which exhibited a G1/S DNA content by FACS
      analysis, suggesting that expression of this key cell cycle function was
      dramatically altered by viral functions. These data demonstrate that contrary to
      expectations, cytomegalovirus inhibits normal cell cycle progression. The host
      cell is blocked prior to S phase to provide a favorable environment for viral
      replication.

PMID- 8995691
TI  - Expression and maturation of human foamy virus Gag precursor polypeptides.
AB  - In this report, we address the processing of the Gag polypeptides of human foamy
      virus previously reported to be atypical. In the cytoplasm or the nucleus of
      infected cells as well as in free virus particles, two Gag precursor polypeptides
      were identified at approximately 72 and 68 kDa, p72 giving rise to p68 by a
      maturation process. Efficient maturation of Gag precursors was observed only in
      two situations: (i) during the early steps of virus adsorption and (ii) under
      experimental conditions, including treatment with DNase I, known to dissociate
      actin polymers associated with high ionic strength and ionic detergents. Rather
      than being a defective viral protease function, an association of Gag precursors
      with a cytoskeleton network might be responsible for the low rate of Gag protein
      maturation through inhibition of their cleavage by the protease.

PMID- 8995692
TI  - Detection of HLA-DR associated with monocytotropic, primary, and plasma isolates
      of human immunodeficiency virus type 1.
AB  - This study determined whether HLA-DR was incorporated into human immunodeficiency
      virus type 1 produced in vivo or by primary cultured cells. HLA-DR was associated
      with virions from primary isolates, macrophage cultures, and blood plasma. These
      results represent the first demonstration of major histocompatibility complex
      molecules associated with an in vivo source of virus.

PMID- 8995693
TI  - Selection for retroviral insertions into regulated genes.
AB  - Gene traps can be used to monitor faithfully the changes in gene expression
      accompanying several cellular processes. Here, we present a strategy that
      combines retroviral gene trap vectors, efficient selection schemes based on
      fluorescence-activated cell sorting or dominant positive and negative drug
      selection, and appropriately responsive cell lines in order to enrich for
      retroviral insertions into regulated genes (i.e., genes participating in cellular
      differentiation processes and genes induced by growth factors, drugs, or
      neurotransmitters, etc.). As an example, we applied this approach to the
      identification of insertions into genes activated by a MyoD protein, using a MyoD
      responsive fibroblast line. In a single experiment designed to demonstrate the
      feasibility of this approach, we have been able to screen thousands of gene trap
      integrations and to select those that represent direct or indirect targets of
      MyoD. Distinct patterns of regulation were observed during myogenic
      determination. Sequences flanking the integrations can be rescued with several
      approaches, and they can be used to isolate the host genes or can serve as entry
      points for genome-wide sequencing projects.

PMID- 8995694
TI  - Identification of a replication-competent pathogenic human immunodeficiency virus
      type 1 with a duplication in the TCF-1alpha region but lacking NF-kappaB binding
      sites.
AB  - Multiple human immunodeficiency virus type 1 (HIV-1) sequences with deletions of
      NF-kappaB binding sites at both the 5' and 3' long terminal repeats (LTRs) were
      identified in serial samples collected from an infected individual. The effect of
      this deletion on the level of transcription was studied by transient transfection
      of an LTR-driven luciferase reporter gene and by infection with a full-length
      recombinant HIV-1 containing a luciferase reporter (HIVHXBluc). Detectable levels
      of gene expression were found in both systems, in the presence or absence of the
      viral transactivator Tat. Interestingly, a duplication of a putative TCF-1alpha
      motif was found in place of the NF-kappaB elements in these viruses. Higher
      transcriptional activity was observed with HXBLTR (NF-kappaB intact) than with
      the patient's LTR (NF-kappaB deleted), suggesting that the NF-kappaB binding
      sites may promote optimal levels of viral gene transcription. The ability of
      these viruses with NF-kappaB deleted to replicate and cause substantial decline
      in CD4 cell counts demonstrates that the NF-kappaB binding sites are not
      absolutely required for viral replication or pathogenicity in vivo. These results
      are consistent with the notion that the HIV-1 LTR possesses functional redundancy
      which allows it to interact with multiple transcription factors, thereby ensuring
      viral replication in a variety of cell types.

PMID- 8995696
TI  - The sequence element of the internal ribosome entry site and a 25-kilodalton
      cellular protein contribute to efficient internal initiation of translation of
      hepatitis C virus RNA.
AB  - Translation of hepatitis C virus (HCV) RNA is initiated by internal entry of
      ribosomes into the 5' noncoding region (NCR). This process depends on genomic
      elements within the 5' NCR called the internal ribosome entry site (IRES) and may
      involve host factors. The alpha-branch structure (nucleotides 47 to 67) of the
      HCV IRES is considered a cis-acting element critical for translation initiation
      because it is indispensable for translation in vitro (S. Fukushi, K. Katayama, C.
      Kurihara, N. Ishiyama, F. B. Hoshino, T. Ando, and A. Oya, Biochem. Biophys. Res.
      Commun. 199:425-432, 1994). In order to further characterize the function of the
      alpha-branch, we determined whether sequence exchange within the alpha-branch had
      any effect on translation initiation. An in vitro translation study revealed that
      the stem sequences of this region played an important role in efficient IRES
      function. In addition to several HeLa cell proteins, which had a binding affinity
      for the 5' NCR, a novel 25-kDa protein that specifically interacted with the HCV
      IRES was discovered. The binding affinity of the 25-kDa protein for the 5' NCR
      was correlated with the efficiency of translation initiation of HCV RNA,
      indicating a critical role for the 25-kDa protein in HCV translation.

PMID- 8995695
TI  - Macrophage tropism of human immunodeficiency virus type 1 and utilization of the
      CC-CKR5 coreceptor.
AB  - The recent identification of the CC-CKR5 beta chemokine receptor as a major
      cofactor for entry of macrophage-tropic isolates of human immunodeficiency virus
      type 1 (HIV-1) raises the question of whether macrophage tropism is determined by
      utilization of this chemokine receptor. We observe that in addition to macrophage
      tropic isolates of clades A, B, and E, macrophage-tropic isolates of clade F also
      utilize the CC-CKR5 molecule for entry. However, using single-round replication
      competent reporter viruses carrying the envelope genes of T-cell line-tropic or
      macrophage-tropic phenotypic recombinant and mutant HIV-1 strains in infection of
      stable cell lines that coexpress the CD4 and chemokine receptors, we were unable
      to establish a strict correlation between macrophage tropism and utilization of
      the CC-CKR5 chemokine receptor. This latter finding suggests that a cofactor
      other than CC-CKR5 serves to determine entry into primary macrophages.

PMID- 8995697
TI  - Chaperone functions common to nonhomologous Epstein-Barr virus gL and Varicella
      Zoster virus gL proteins.
AB  - Herpesviruses encode the complex-forming, essential glycoproteins gH and gL.
      Maturation and transport of gH are dependent on coexpression of its chaperone,
      gL. The gL proteins of alpha herpesviruses and gamma herpesviruses do not have a
      significant percentage of amino acid sequence homology. Yet, as we report herein,
      the diverse gL glycoproteins of Epstein-Barr virus (EBV) and varicella-zoster
      virus (VZV) were functionally interchangeable, although membrane expression and
      maturation of gH were separate functions for these viruses. In VZV both functions
      were performed by a single protein. EBV required two separate glycoproteins, one
      of which can be replaced by its homologous protein from VZV, a distant relative
      of EBV. Collectively, these results suggested that VZV gL is a simpler form of
      the gL chaperone protein than EBV gL.

PMID- 8995698
TI  - Late expression of a beta chemokine homolog by murine cytomegalovirus.
AB  - A gene (HJ1) present in murine cytomegalovirus (MCMV) encodes an open reading
      frame (ORF) whose predicted amino acid sequence shows homology to the beta (or C
      C) class of chemotactic cytokines known as chemokines. The region of homology is
      located in the carboxyl-terminal portion of the 116-amino-acid ORF. A 0.9-kb RNA
      transcript corresponding to the HJ1 gene is expressed in MCMV-infected
      fibroblasts and macrophages as a member of the late kinetic class of virally
      encoded transcripts. A transcriptional start site is located between the third
      and fourth methionine residues in the ORF, predicting a primary amino acid
      structure, starting at the fourth methionine residue, which includes a possible
      signal peptide as well as conserved cysteine residues typical for mammalian beta
      chemokines. The RNA transcript is polyadenylated, suggesting that it can undergo
      translation within the cytoplasm of an MCMV-infected cell. We speculate that
      expression of the chemokine homolog at late times in the MCMV replication cycle
      plays a role in MCMV pathogenesis, possibly by action as a chemotactic agonist or
      antagonist or by alteration of the activation or differentiation state of a
      susceptible cell such as a macrophage.

PMID- 8995699
TI  - Antibody cross-reactivity with CD46 and lack of cell surface expression suggest
      that moesin might not mediate measles virus binding.
AB  - The binding of antimoesin antibodies from ascites fluids to the surfaces of human
      and rodent cells was found to parallel the level of CD46 expression. No such
      reactivity was detected with a purified antimoesin antibody which recognized
      intracellular moesin. In Western blots, antimoesin antibodies were found to react
      with solubilized CD46 and a recombinant soluble form of CD46. Antimoesin
      antibodies also reacted with CD46/CD4 molecules containing only the SCR I and II
      domains required for measles virus (MV) hemagglutinin binding onto CD46. We
      suggest that the weak cross-reactivity of antimoesin antibodies with CD46
      explains the inhibitory effect of these antibodies on MV entry and that moesin is
      not directly involved in MV binding.

PMID- 8995700
TI  - Na, an autoproteolytic product of the herpes simplex virus type 1 protease, can
      functionally substitute for the assembly protein ICP35.
AB  - The herpes simplex virus type 1 (HSV-1) protease and its substrate, the assembly
      protein ICP35, are involved in virion maturation. Both proteins are encoded by a
      single open reading frame but are translated independently from 3'-coterminal
      mRNAs of different sizes and are in frame. The herpesvirus shell assembles around
      an internal scaffold which is subsequently lost during packaging of the viral
      genome. The scaffold is composed of ICP35, which is the major component, and
      autoproteolytically processed forms of the viral protease containing sequences
      common to ICP35 (Nb). In the baculovirus system, HSV-1 intact capsids can be
      formed in the presence of the protease or ICP35, indicating that the protease may
      substitute for ICP35 (Thomsen et al., J. Virol. 68:2442-2457, 1994). This is
      further supported by the fact that ICP35, in contrast to the protease, is not
      absolutely essential for viral growth. The processed intermediate of the protease
      analogous to ICP35 is the 388-amino-acid (aa) protein, Na, which is an N-terminal
      59-aa extension of the 329-aa ICP35. To directly examine whether Na can
      functionally substitute for ICP35 during viral replication, we first constructed
      a mutant virus, Na delta35, in which 35 aa from the N terminus of Na were
      deleted. Phenotypic analysis of the mutant showed that this deletion had no
      effect on protease function. The function of Na was further examined by
      construction of a plasmid expressing Na alone and testing its ability to
      complement the growth of the mutant Prb virus in the absence of ICP35. Our
      results demonstrate that Na can functionally substitute for ICP35 during viral
      replication.

PMID- 8995701
TI  - Human carcinoembryonic antigen and biliary glycoprotein can serve as mouse
      hepatitis virus receptors.
AB  - Receptors for murine coronavirus mouse hepatitis virus (MHV) are members of the
      murine carcinoembryonic antigen (CEA) gene family. Since MHV can also infect
      primates and cause central nervous system lesions (G. F. Cabirac et al., Microb.
      Pathog. 16:349-357, 1994; R. S. Murray et al., Virology 188:274-284, 1992), we
      examined whether human CEA-related molecules can be used by MHV as potential
      receptors. Transfection of plasmids expressing human carcinoembryonic antigen
      (hCEA) and human biliary glycoprotein into COS-7 cells, which lack a functional
      MHV receptor, conferred susceptibility to two MHV strains, A59 and MHV-2. Domain
      exchange experiments between human and murine CEA-related molecules identified
      the immunoglobulin-like loop I of hCEA as the region conferring the virus-binding
      specificity. This finding expands the potential MHV receptors to primate species.

PMID- 8995703
TI  - Rhodanine resistance and dependence of echovirus 12: a possible consequence of
      capsid flexibility.
AB  - Recombinant viruses of echovirus 12 carrying mutations of a rhodanine-resistant
      or -dependent variant, were investigated, and five single mutations each inducing
      a rhodanine-resistant or -dependent phenotype were defined. Four mutations are
      localized in the capsid protein VP1, and the fifth exchange is in VP4. All
      original and recombinant viruses were shown to be stabilized by the antiviral
      drug rhodanine against heat inactivation. Hence, resistant and dependent variants
      still seem able to bind rhodanine, and apparently none of the exchanges affects
      the putative drug binding site. We hypothesize that drug resistance and
      dependence are consequences of an increased flexibility of the virus capsid.

PMID- 8995702
TI  - Inhibition of human immunodeficiency virus fusion by a monoclonal antibody to a
      coreceptor (CXCR4) is both cell type and virus strain dependent.
AB  - CXCR4 (also termed fusin, LESTR, or HUMSTR) is a member of the G-protein-coupled
      chemokine receptor family with seven membrane-spanning domains. CXCR4 acts as a
      coreceptor for syncytium-inducing human immunodeficiency virus type 1 (HIV-1)
      strains, conferring entry into CD4+ cells. We show here that a novel mouse
      monoclonal antibody (12G5) that recognizes CXCR4 blocked cell-to-cell fusion and
      cell free-virus infection of CXCR4+ CD4+ RD rhabdomyosarcoma cells by seven HIV-1
      and HIV-2 strains that had various cell tropisms for different CD4+ human cell
      types. Yet the majority of the members of the same virus panel resisted 12G5
      inhibition on T-cell lines. When inhibition was observed on these cell types, it
      was both cell type and virus strain dependent. In at least one situation, 12G5
      failed to block LAI infection of cells expressing CXCR4 as the only available
      coreceptor. Our observations suggest that CXCR4 could be processed or presented
      differently depending on the cell type, allowing some strains to evade 12G5
      inhibition. Alternatively, since several of the viruses could infect certain
      CXCR4- CD4+ cell lines, it is conceivable that alternative coreceptors are
      active, enabling individual HIV strains to choose between compatible coreceptors
      during entry into cells. Moreover, the strain dependency of 12G5 inhibition
      implies that the interaction of different HIVs with CXCR4 varies.

PMID- 8995705
TI  - Human herpesvirus 7 infection of lymphoid and myeloid cell lines transduced with
      an adenovirus vector containing the CD4 gene.
AB  - It has been reported recently that CD4 is a major component of the receptor for
      human herpesvirus 7 (HHV-7), which has been newly identified as a T-lymphotropic
      virus. To investigate further the role of CD4 in HHV-7 infection, we examined the
      susceptibility to HHV-7 infection of various CD4-negative or weakly positive cell
      lines into which the cDNA for CD4 was transferred using an adenovirus vector
      (Adex1CACD4). Of 13 cell lines transduced with Adex1CACD4, including T-lymphoid,
      B-lymphoid, monocytoid, and myeloid cell lines, one T-lymphoid cell line, one
      monocytoid cell line, and two cell lines established from the blast crisis of
      chronic myelogenous leukemia showed high susceptibility to HHV-7 infection. Taken
      together with the results of previous studies, these data suggest strongly that
      CD4 is a major component of the binding receptor for HHV-7. This study also shows
      that HHV-7 may be able to infect CD4-positive hematopoietic precursor cells as
      well as T lymphocytes.

PMID- 8995704
TI  - Analysis of the 2-kilobase latency-associated transcript expressed in PC12 cells
      productively infected with herpes simplex virus type 1: evidence for a stable,
      nonlinear structure.
AB  - The major latency-associated transcript (LAT) expressed in PC12 cells
      productively infected with herpes simplex virus type 1 is a 2-kb,
      nonpolyadenylated RNA molecule that accumulates in the nuclei of infected cells.
      In actinomycin D-treated cells, the 2-kb LAT gene transcript has a half-life
      considerably greater than 12 h. After polyacrylamide gel electrophoresis, two
      species of the transcript were observed, a major species that was retarded in the
      gel and a minor species that migrated as a 1.96-kb RNA molecule. RNase H
      digestion after hybridization of the RNA with an oligonucleotide complementary to
      positions -80 to -101 relative to the 3' end of the 2-kb LAT gene transcript
      changed the mobility of the retarded species into that of the rapidly migrating
      species. Our data indicate that the 2-kb LAT gene transcript expressed in
      productively infected PC12 cells is present in a stable, nonlinear form.

PMID- 8995706
TI  - Construction of a genome-length cDNA clone for human astrovirus serotype 1 and
      synthesis of infectious RNA transcripts.
AB  - We have constructed a genome-length cDNA clone for human astrovirus serotype 1.
      When a human colon cancer-derived cell line, CaCo-2, is transfected with RNA
      transcribed in vitro from this cDNA clone, infectious virus is produced at titers
      close to those observed after infection with intact astrovirus. A rodent cell
      line, BHK, which is largely refractory to astrovirus infection, was found to
      support efficient growth of the virus if transfected with viral RNA. The high
      transfection efficiency seen in the BHK cells allows studies of the viral
      replication in the transfected cells and thus should prove useful for the
      characterization of noninfectious astroviral mutants.

PMID- 8995707
TI  - Induction of CD4 expression and human immunodeficiency virus type 1 replication
      by mutants of the interferon-inducible protein kinase PKR.
AB  - Replication of the human immunodeficiency virus type 1 (HIV-1) is inhibited by
      interferons (IFNs), and the IFN-inducible protein kinase PKR is thought to
      mediate this effect by regulating protein synthesis. Here we report that ectopic
      expression of dominant negative PKR mutants in Jurkat cells induces HIV-1
      replication. Specifically, expression of CD4 is upregulated by the PKR mutants,
      and this correlates with an induction of HIV-1 binding and proviral DNA synthesis
      upon HIV-1 infection. Moreover, activation of NF-kappaB was induced by an RNA
      binding-defective mutant of PKR. Thus, it appears that PKR, in addition to
      translational control, is involved in HIV-1 replication by modulating virus
      binding through the regulation of CD4 expression and virus gene expression
      through the activation of NF-kappaB.

PMID- 8995708
TI  - Characterization of monoclonal antibodies raised against p300: both p300 and CBP
      are present in intracellular TBP complexes.
AB  - The amino terminus of the adenovirus E1A protein is involved in E1A transforming
      functions, repression of tissue-specific gene expression, and E1A-mediated
      enhancer repression. These N-terminal functions are associated with the ability
      of this region of E1A to bind to p300 and CBP, two closely related cellular
      proteins thought to function as transcriptional adaptor molecules. Here we
      describe the characterization of a panel of 11 monoclonal antibodies raised
      against E1A-affinity-purified 300-kDa proteins. The panel can be divided into two
      groups based on immunoprecipitation patterns. The first group consists of five
      p300/CBP-cross-reactive and two p300-specific monoclonal antibodies, all of which
      immunoprecipitate p300 and/or CBP without associated cellular proteins. In
      contrast, the second group immunoprecipitates p300 or both p300 and CBP in
      association with a complex of at least seven other cellular proteins. Taking
      advantage of the specificities of these monoclonal antibodies, we have identified
      both p300 and CBP in in vivo complexes with TBP, a finding consistent with a role
      for both p300 and CBP in promoting interactions between upstream promoter
      elements and the basal transcription apparatus.

PMID- 8995709
TI  - Structure of replicating hepatitis C virus (HCV) quasispecies in the liver may
      not be reflected by analysis of circulating HCV virions.
AB  - We have analyzed the population of hepatitis C virus (HCV) sequences in paired
      liver and serum samples from four patients with chronic hepatitis C. Sequences
      from three different biopsy specimens from a liver explant from one patient were
      compared with each other and with the circulating sequences. Our results
      demonstrate that the circulating quasispecies does not necessarily reflect the
      viral population replicating in the liver and that this is not due to a
      macroscopic anatomic compartmentalization of HCV replication. This finding has
      important implications for the pathogenesis and natural history of chronic HCV
      infection.

PMID- 8995710
TI  - Recovery of cytopathogenic and noncytopathogenic bovine viral diarrhea viruses
      from cDNA constructs.

PMID- 8995711
TI  - State- and sex-specific prevalence of selected characteristics--Behavioral Risk
      Factor Surveillance System, 1992 and 1993.
AB  - PROBLEM/CONDITION: Much chronic disease and injury morbidity and mortality is
      associated with high-risk behaviors (e.g., cigarette smoking, excessive alcohol
      consumption, and physical inactivity) and with lack of preventive health care
      (e.g., screening for cancer). States use the Behavioral Risk Factor Surveillance
      System (BRFSS) to collect data about these modifiable health behaviors and to
      monitor trends and significant changes in their populations over time. REPORTING
      PERIOD: 1992 and 1993. DESCRIPTION OF SYSTEM: The BRFSS is a state-based
      telephone survey of the civilian, noninstitutionalized, adult (persons > or = 18
      years of age) population. In 1992, 48 states and the District of Columbia
      participated in the BRFSS; in 1993, 49 states and the District of Columbia
      participated. Several questions were added to the BRFSS in 1993. RESULTS: As in
      previous years, state-specific variations occurred in the prevalence of high-risk
      behaviors, awareness of certain medical conditions, use of preventive health
      services, and health-care coverage. In 1993, 4.0% (range: 1.4% - 6.4%) of adults
      reported riding with a driver who had had too much alcohol to drink. The
      percentage of persons > or = 50 years of age who had ever had a proctoscopic
      examination ranged from 25.6% to 51.5% (median: 36.8%). Among adults > or = 65
      years of age, 27.4% (range: 18.5 % - 40.0%) had ever had a pneumococcal
      vaccination, and 49.9% (range: 28.7% - 66.2%) had had an influenza vaccination
      within the past 1 year. INTERPRETATION: The variations in prevalence across
      states likely reflect socioeconomic differences, differences in state laws
      enacted to discourage risky behaviors, different levels of effort to screen for
      certain types of cancer or risk factors for other diseases, and other factors.
      ACTION TAKEN: States will continue to use the BRFSS to collect data about health
      behaviors. Analysis of these data will enable states to monitor factors that may
      affect the rate of chronic disease and injury mortality and morbidity and to
      develop public health policies to address these problems.

PMID- 8995713
TI  - Renal cysts, renal cancer and von Hippel-Lindau disease.

PMID- 8995712
TI  - Understanding the nature of renal disease progression.
AB  - Animal and human proteinuric glomerulopathies evolve to terminal renal failure by
      a process leading to progressive parenchymal damage, which appears to be
      relatively independent of the initial insult. Despite the fact that the
      mechanism(s) leading to renal disease progression has been only partially
      clarified, several studies have found that the amount of urinary proteins (taken
      to reflect the degree of protein trafficking through the glomerular capillary)
      correlated with the tendency of a given disease to progress more than the
      underlying renal pathology. On the other hand, dietary protein restriction and
      ACE inhibitors were capable of limiting the progressive decline in GFR to the
      extent that they could effectively lower the urinary protein excretion rate. A
      constant feature of proteinuric nephritis is also the concomitant presence of
      tubulointerstitial inflammation. So far it was not clear if this is a reaction to
      the ischemic obliteration of peritubular capillaries that follows glomerular
      obsolescence or whether albumin and other proteins that accumulated in the
      urinary space are indeed instrumental for the formation of the interstitial
      inflammatory reaction. In recent years several studies have convincingly
      documented that excessive and sustained protein trafficking could have an
      intrinsic renal toxicity. Here we have reviewed the abundant evidence in the
      literature that the process of reabsorption of filtered proteins activates the
      proximal tubular epithelium. Biochemical events associated with tubular cell
      activation in response to protein stress include up-regulation of inflammatory
      and vasoactive genes such as MCP-1 and endothelins. The corresponding molecules
      formed in an excessive amount by renal tubuli are secreted toward the basolateral
      compartment of the cell and give rise to an inflammatory reaction that in most
      forms of glomerulonephritis consistently precede renal scarring.

PMID- 8995714
TI  - Nonenzymatically glycated albumin (Amadori adducts) enhances nitric oxide
      synthase activity and gene expression in endothelial cells.
AB  - Hyperglycemia is considered to induce diabetic nephropathy through nonenzymatic
      glycation of proteins. Since hyperfiltration is likely to be the mechanism
      initiating the glomerular lesions, we investigated the effects of Amadori glucose
      adducts in serum albumin on the production of vasoactive mediators, including
      nitric oxide (NO) and eicosanoids, by endothelial cells (EC). Amadori adducts of
      glycated albumin induced a dose-response increase in NO synthase activity of
      murine endothelioma cells, up to 16.4 +/- 2.1-fold increase of basal values (P <
      0.0001) at concentrations of 35 mg/ml mimicking physiological serum albumin
      concentration, and 4.6 +/- 0.8-fold increase at 17 mg/ml (P < 0.001). The effect
      was still detectable with glycated albumin 1.7 mg/ml, which approaches its
      estimated concentration in diabetic serum (1.6 +/- 0.3-fold increase, P < 0.05)
      The phenomenon was reproducible in human umbilical vein endothelial cells, though
      to a lesser extent, and further studies on murine EC were employed. The mRNA
      encoding for inducible NO synthase was overexpressed in EC incubated with Amadori
      adducts of glycated albumin in comparison to native albumin. Glycated albumin
      induced increased mRNA expression and synthesis of TNF-alpha. The stimulatory
      effect induced by glycated albumin on NO synthase activity was almost completely
      inhibited by anti TNF alpha antibodies. 3H-thymidine incorporation by EC was
      significantly inhibited when cells were grown in presence of glycated albumin (P
      < 0.001), and the phenomenon was abolished by the coincubation of the NO
      competitive inhibitor L-NAME. The early glycosylation products increased
      thromboxane production (P < 0.001), while prostaglandin E2 synthesis was
      unaffected. These data indicate that Amadori products of glycated albumin
      modulate NO synthase activity and eicosanoid balance in EC. These effects may be
      relevant to the hemodynamic changes in the early phases of diabetic nephropathy
      and in the lasting progression to sclerosis.

PMID- 8995715
TI  - Inhibition of angiotensin-converting enzyme modulates structural and functional
      adaptation to loop diuretic-induced diuresis.
AB  - The roles of elevated cell sodium concentrations and the angiotensin-aldosterone
      system (AAS) in the structural and functional adaptation of the distal tubule and
      collecting duct system to a chronic increase of sodium delivery were examined
      using electron microprobe and quantitative morphologic/stereologic analyses.
      Studies were performed on rats given the loop diuretic torasemide acutely (20
      min) or chronically (12 days), either alone or in combination with the
      angiotensin-converting enzyme (ACE) inhibitor, enalapril. In the sodium-absorbing
      cells of the distal tubule and cortical collecting duct-that is, in distal
      convoluted tubule (DCT), connecting tubule (CNT) and principal cells-an acute
      increase in sodium delivery caused a significant rise in intracellular sodium
      concentration and rubidium uptake, the latter an index of in vivo Na,K(Rb)-ATPase
      activity. The elevated cell sodium concentrations returned to, or close to,
      control values during chronic torasemide treatment. Intracellular rubidium
      concentrations, measured after a 30-second rubidium exposure, were not different
      from controls in DCT and CNT cells but were still higher in principal cells.
      Since, however, the distribution space for rubidium was significantly increased
      in chronic torasemide animals, rubidium uptake, and hence Na,K-ATPase activity,
      must have increased in proportion to cell volume in DCT and CNT cells, but more
      than proportionately in principal cells. When ACE was inhibited during chronic
      torasemide, the epithelial volume of DCT and cortical collecting duct (CCD) was
      increased mainly by lengthening and not, as was the case in rats given torasemide
      alone, by thickening of the tubule wall. Adaptation of the proximal tubule
      exclusively by lengthening was not affected by inhibition of the ACE. These data
      indicate that changes in cell ion composition may participate in initiating cell
      processes leading to adaptation of distal nephron segments to chronically
      increased salt delivery. Inhibition of the ACE reverses the torasemide-induced
      increase in apparent Na pump density in principal cells and seems to shift the
      relationship between hypertrophy and hyperplasia noted in DCT and CCD after
      chronic torasemide in favor of hyperplasia.

PMID- 8995716
TI  - Effects of reduced renal perfusion pressure and acute volume expansion on
      proximal tubule and whole kidney angiotensin II content in the rat.
AB  - In previous studies high luminal concentrations of angiotensin II (Ang II) were
      found in rat proximal tubules. The physiological role of intraluminal Ang II
      remains to be established. In the present study, we investigated whether the
      luminal angiotensin II concentration in the proximal tubules ([Ang II]prox) can
      be modulated. Micropuncture studies were performed in control rats (C, N = 8) and
      rats subjected to acute volume expansion (VE, N = 8) or reduced renal perfusion
      pressure (RRP, N = 7). Changes in [Ang II]prox were compared to changes in whole
      kidney Ang II content ([ANG II]kidney) and the plasma concentration ([Ang II]
      plasma). In C rats, [Ang II]prox was 460 +/- 48 pmol/liter (10 to 20 times lower
      than hitherto reported), while [Ang II]kidney and [Ang II]plasma were 369 +/- 81
      pmol/kg and 90 +/- 29 pmol/liter, respectively. In agreement with previous data,
      VE failed to suppress [Ang II]prox (674 +/- 132 pmol/liter), while at the same
      time [Ang II]kidney (42 +/- 10 pmol/kg) and [Ang II]plasma (12 +/- 3 pmol/liter)
      were markedly suppressed. This points to dissociated regulation of [Ang II] in
      the renal luminal compartment on the one hand and the extraluminal renal and
      systemic plasma compartments on the other hand. During RRP, [Ang II]prox
      increased significantly to 1675 +/- 465 pmol/liter. No dissociation between the
      three compartments was observed in this situation, as [Ang II]kidney (969 +/- 85
      pmol/kg) and [Ang II]plasma (245 +/- 72 pmol/liter) increased in parallel. In
      summary, we confirm that Ang II is present in proximal tubules of rat kidneys at
      concentrations which exceed those in plasma. Its concentration could be modulated
      (approximately 3.5 increase) by reduction of renal perfusion pressure but not by
      acute volume expansion. In the latter condition, we observed a clear dissociation
      from Ang II generation in the extraluminal renal compartment, as whole kidney Ang
      II content was markedly suppressed.

PMID- 8995717
TI  - Relationship between MRI and morphometric kidney measurements in diabetic and non
      diabetic rats.
AB  - The aim of the present study was to determine the applicability of magnetic
      resonance imaging (MRI) as a non-invasive measure of kidney volume in vivo in
      diabetic and non-diabetic rats. Magnetic resonance, T1 weighted Spin Echo, images
      were obtained after injection of contrast in anesthetized control (N = 14) and
      hyperglycemic streptozotocin (STZ)-diabetic rats (N = 14). On MRI imaging the
      total kidney, cortex, medullary and pelvic volumes were calculated. Immediately
      after MRI measurements the left kidneys were removed before weighing either as a
      clamped kidney weight (that is, the kidney containing blood and urine) or as a
      wet kidney weight (the kidney drained of blood and urine), while the right
      kidneys were perfusion-fixed for morphometric measurements. On thin kidney slices
      obtained from perfusion-fixed kidneys the cortex, medullary and pelvic fractions
      were measured and subsequently the cortex, medulla and pelvic volumes were
      calculated. The cortical volume was measured according to three different
      approaches. The corticomedullary boundary was defined either to the arcuate
      arteries, to a curved line following the glomeruli, or to a line at the top of
      the medullary rays. Both in control and diabetic rats, MRI measured kidney
      volumes were similar to the volume of perfusion-fixed kidneys, while the clamped
      kidney weight, and in particular the wet kidney weights, were smaller than the
      MRI obtained volumes. Good agreement was found between the MRI measured cortex
      and medulla volumes when the cortex was defined to the top of the medullary rays
      in the morphometric analysis. In conclusion, the present study demonstrates that
      MRI allows a reliable non-invasive estimate of renal morphology at a macroscopic
      level in both diabetic and non-diabetic rats.

PMID- 8995718
TI  - Role of glomerular mechanical strain in the pathogenesis of diabetic nephropathy.
AB  - Glomerular rigidity limits the glomerular expansion and mesangial cell (MC)
      stretch induced by variations in intracapillary pressure. In tissue culture, MC
      stretch stimulates synthesis of extracellular matrix components (ECM). Therefore,
      altered glomerular rigidity in diabetes may influence ECM accumulation by
      modulating the glomerular distention and MC stretch associated with glomerular
      hypertension. An ambient of high glucose concentration per se also enhances MC
      formation of ECM, possibly altering the cellular response to mechanical stretch.
      In this study, compliance was measured in isolated perfused glomeruli from
      streptozotocin-injected rats at four days (4d-D), five weeks (5w-D) and six
      months (6m-D) after induction of diabetes. In addition, collagen metabolism
      induced by stretch was investigated in MC cultured in 8 and 35 mM glucose
      concentrations. Glomerular compliance was normal in 5w-D rats and moderately
      increased in 4d-D (16%) and 6m-D animals (14%). As compared to static cultures.
      MC stretch increased total collagen synthesis (8 mM, 50%; 35 mM, 27%) and
      catabolism. However, while the fraction of newly formed collagen being
      catabolized increased in 8 mM-stretched cultures, in 35 mM-stretched it was
      unchanged. This resulted in marked increase in the net collagen accumulated in
      the incubation medium (4 vs. 24%) and cell layer 5 vs. 15%) only in the latter.
      In diabetes, the largely unaltered glomerular stiffness renders hypertension
      induced MC stretch unopposed. More importantly, the accumulation of ECM caused by
      any degree of mechanical strain is greatly aggravated in a milieu of high glucose
      concentration.

PMID- 8995719
TI  - Role of interleukin-6 in mediating mesangial cell proliferation and matrix
      production in vivo.
AB  - Mesangial cell proliferation and matrix overproduction characterize many
      progressive glomerular diseases. Based on currently available data, the role of
      interleukin-6 (IL-6) in mediating mesangial cell proliferation and matrix
      production is controversial. The present study attempts to clarify this issue by
      showing that: (1) IL-6 knock out mice develop a normal glomerular architecture
      and in particular a normal mesangium. (2) Mesangioproliferative
      glomerulonephritis induced by Habu snake venom is equally severe in IL-6 knock
      out mice as in control mice. (3) A continuous seven-day intraperitoneal infusion
      of 50 micrograms recombinant human IL-6 into rats with a prior minimal
      (subnephritogenic) injury to mesangial cells does not induce glomerular cell
      activation, cell proliferation, matrix production, leukocyte influx, platelet
      influx or proteinuria. (4) A continuous seven-day IL-6 infusion into rats with
      mesangioproliferative nephritis (anti-Thy 1.1 nephritis) increases matrix protein
      transcription in the absence of detectable effects on matrix protein accumulation
      and otherwise has no effect on the natural course of the disease. We conclude
      from these findings that IL-6 is not an important mediator of mesangial cell
      proliferation and matrix overproduction in vivo, and that currently little
      rationale exists to advocate anti-IL-6 therapy in mesangioproliferative disease
      states.

PMID- 8995720
TI  - Up-regulation of tubular epithelial interleukin-12 in autoimmune MRL-Fas(lpr)
      mice with renal injury.
AB  - Phagocyte-derived interleukin-12 (IL-12) is a key cytokine that induces the
      development of an effective Th1 type immune response in various inflammatory and
      infectious disorders. To determine the importance of IL-12 in the pathogenesis of
      autoimmune renal injury we examined the renal production of this heterodimeric
      cytokine in the MRL-Fas(lpr) lupus nephritis model. Compared with normal mice RT
      PCR products encoding both the p35 and p40 subunits of IL-12 were markedly
      increased in the kidney of MRL-Fas(lpr). Immunofluorescence staining demonstrated
      expression of the IL-12 p75 heterodimer on isolated infiltrating mononuclear
      cells and also on proximal tubular epithelial cells in MRL-Fas(lpr) but less in
      normal mice kidneys. The enhanced expression of IL-12 correlated with an
      increased intrarenal transcription of IFN-gamma. The p35 and p40 transcripts and
      soluble IL-12 p75 protein were also produced by cultured TEC. In addition,
      membrane bound IL-12 was detected on Tec. We conclude that IL-12 production is
      significantly up-regulated in MRL-Fas(lpr) lupus nephritis. In addition to
      mononuclear cells, TEC are an important source of IL-12 and could thereby
      participate in the development of a Th1 type immune response in autoimmune renal
      injury.

PMID- 8995721
TI  - Alteration of cytosolic calcium induced by angiotensin II and norepinephrine in
      mesangial cells from diabetic rats.
AB  - To evaluate functional alterations of mesangial cells induced by diabetes (DMC),
      we observed the changes of cytosolic calcium ([Ca]i) in response to the
      vasoconstrictor agonists angiotensin II (Ang II) and norepinephrine (NOR). DMC
      were obtained from rats with streptozotocin-induced diabetes, cultured in normal
      medium and identified as mesangial cells (MC) in the third subculture. [Ca]i was
      measured using fura-2 as a fluorophore. Basal calcium levels (60 to 80 nM) in DMC
      were not different from control mesangial cells (CMC). The high glucose (30 mM)
      medium concentration reduced the response of CMC and DMC to Ang II and NOR. This
      was not an osmotic effect since mannitol did not alter these responses. When DMC
      were stimulated with Ang II, a desensitized response was always observed, with a
      transient variation of [Ca]i (N = 6, P < 0.05). In contrast, a non-desensitized
      response with a sustained pattern of [Ca]i increases was obtained in NOR
      stimulated DMC. Therefore, the present results suggest that DMC show a modified
      response to stimulation of the Ang II receptor, which is expressed phenotypically
      in culture by desensitization. Furthermore, these alterations induced by diabetes
      environment in MC in vivo were maintained in vitro despite a long period
      (approximately 5 months) in which the cells were grown in normal culture medium.

PMID- 8995722
TI  - Th1 responsiveness to nephritogenic antigens determines susceptibility to
      crescentic glomerulonephritis in mice.
AB  - The pattern of glomerulonephritis (GN) developing in response to a planted
      antigen (sheep anti-mouse GBM globulin) was compared in two strains of mice which
      demonstrated either a predominant Th1 (C57BL/6) or Th2 (BALB/c) response to this
      antigen. GN was induced with a subnephritogenic i.v. dose of sheep anti-mouse GBM
      globulin in mice presensitized to sheep globulin. Sensitized C57BL/6 mice showed
      pronounced cutaneous delayed-type hypersensitivity (DTH) following the challenge
      with sheep globulin, low titers of circulating anti-sheep globulin antibody and
      high interferon gamma (IFN-gamma) and low interleukin 4 (IL-4) production by
      splenic T cells, consistent with a predominant Th1 pattern of immune response.
      Sensitized BALB/c mice did not develop DTH following cutaneous challenge with
      sheep globulin, had higher circulating anti-sheep globulin antibody titers, and
      showed high IL-4 and low IFN gamma production by splenic T cells compared with
      C57BL/6 mice, consistent with a predominant Th2 response. In C57BL/6 mice, GN
      developing in response to sheep globulin exhibited a severe crescentic pattern
      with prominent glomerular T cell and macrophage influx and fibrin deposition. In
      vivo depletion with a monoclonal anti-CD4 antibody demonstrated that this injury
      was T helper cell dependent. Treatment with monoclonal anti-mouse IFN gamma
      antibody significantly reduced glomerular injury and crescent formation and
      attenuated the cutaneous DTH response. GN induced by the same protocol in BALB/c
      mice exhibited pronounced glomerular IgG and complement deposition. Crescent
      formation, fibrin deposition, and glomerular T cell and macrophage infiltration
      were significantly less than observed in C57BL/6 mice, and injury was not T cell
      dependent in the effector phase. These data suggest that the pattern of
      glomerular injury induced by a planted antigen can be determined by the balance
      of T helper cell subset activation. A Th1 response induces a severe crescentic
      pattern of GN, which like cutaneous DTH, is T helper cell and IFN gamma
      dependent.

PMID- 8995723
TI  - Prorenin activation and prohormone convertases in the mouse As4.1 cell line.
AB  - The precise identification of prorenin-processing enzymes has been hampered by
      the very low abundance of juxtaglomerular cells in the kidney. Recently, an
      immortalized renin-producing renal tumor cell line (As4.1) has been proposed as a
      model to carry out such studies. Despite the fact that they contain secretory
      granules, we found no evidence (on the basis of enzymatic assays of renin
      activity in the supernatant of the cells and of immunoprecipitations experiments)
      that the As4.1 cells can secrete active renin through the regulated pathway.
      As4.1 cells produce only renin-1, as they derive from a strain of mice expressing
      only one renin gene. However, stable transfection of these cells with a renin-2
      expression plasmid increased the capacity of this cell line to secrete active
      renin in the regulated pathway. Northern blot and reverse transcriptase
      polymerase chain reaction amplification (RT-PCR) assays revealed that furin,
      PACE4 and PC5 were the only members of the proprotein convertase (PC) family to
      be present in these cells. As PC5 is the only such enzyme with the demonstrated
      ability to process mouse prorenin 2, it may constitute a candidate enzyme for the
      processing of prorenin-2 in mouse juxtaglomerular cells. However, it is not
      likely to be involved in the processing of mouse prorenin 1.

PMID- 8995724
TI  - pp60c-src is required for the induction of a quiescent mesangial cell phenotype.
AB  - The tyrosine kinase c-src associates with growth factor receptors, focal contacts
      and cytoskeletal proteins and is involved in signaling events. The aim of this
      study was to investigate the role of src in the regulation of mesangial cell (MC)
      proliferation and differentiation in three-dimensional (3D) culture in collagen
      gels. Using retroviral gene transfer we have overexpressed wild-type c-src, a
      kinase-negative c-src mutant (c-src295) and transforming v-src in MC. The MC
      differentiation in 3D culture was characterized by the formation of a
      nonproliferating multicellular network in control cells and in cells expressing
      wild-type c-src. Immunoblotting demonstrated a rapid down-regulation of the alpha
      smooth muscle actin expression. The kinase-negative MC (c-src295) failed to
      differentiate, maintained a significant proliferative rate, and the alpha-smooth
      muscle actin expression remained stable during 3D culture. MC transformed with v
      src showed a high level of tyrosine phosphorylation and proliferation in 3D
      culture. Analyses of proteins involved in cell cycle regulation demonstrated
      dephosphorylation of the retinoblastoma protein (Rb) during 3D culture in control
      and c-src transfected cells. Expression of v-src resulted in sustained Rb
      phosphorylation. Zymographic analysis of plasminogen activator (u-PA) revealed an
      inhibition of u-PA secretion in MC transfected with c-src295. These results
      indicate that c-src exerts regulatory effects on MC proliferation, cytoskeletal
      organization, matrix proteases and differentiation. Targeted manipulation of the
      c-src kinase may be useful in modulating MC behavior in vivo.

PMID- 8995725
TI  - Angiotensin converting enzyme gene polymorphism and renal hemodynamic function in
      early diabetes.
AB  - An insertion/deletion (I/D) of the human angiotensin converting enzyme (ACE) gene
      is a major determinant of circulating ACE levels. Recent studies suggest that the
      ACE I/D polymorphism may influence the risk of developing nephropathy in patients
      with insulin dependent diabetes mellitus (IDDM), although the mechanism
      responsible for the effect is unknown. Since an early increase in glomerular
      filtration rate (GFR) may also be a risk factor for the development of diabetic
      nephropathy, we sought to determine if the ACE I/D polymorphism influenced renal
      hemodynamic function in patients with IDDM. Genomic DNA was obtained from 39
      normotensive male and female patients with uncomplicated IDDM (mean duration 3.4
      years; range 1 to 6 years), and from 20 non diabetic control subjects. The ACE
      I/D polymorphism was determined using the polymerase chain reaction. Subjects
      were divided into three groups based on their ACE genotype. Values for GFR, renal
      plasma flow (ERPF), filtration fraction, and renal vascular resistance were
      determined in both groups using classic inulin and paraaminohippurate clearance
      techniques. Blood glucose was maintained between 4 to 6 mmol/liter in the
      patients with IDDM using a modified euglycemic clamp technique. Mean values for
      GFR were significantly greater in patients homozygous for the I allele (143 +/- 7
      ml/min/1.73 m2) compared to patients homozygous for the D allele (121 +/- 3
      ml/min/1.73 m2, P < 0.01), while the mean GFR values for the heterozygous
      patients were intermediate. ERPF was also significantly greater in patients
      homozygous for the I allele (850 +/- 103 ml/min/1.73 m2) compared to patients
      homozygous for the D allele (672 +/- 31 ml/min/1.73 m2, P < 0.04), while there
      were no differences in the values for mean arterial pressure, glycosylated
      hemoglobin, or albumin excretion rates amongst the groups. There was no dominant
      effect of the ACE gene I/D polymorphism in the control group. These results
      suggest that: (1) the ACE gene I/D polymorphism influences glomerular filtration
      and renal plasma flow rates in patients with early uncomplicated IDDM; and (2)
      differences in renal hemodynamic function do not appear to explain the protection
      against the development of diabetic nephropathy offered by the I allele.

PMID- 8995726
TI  - Regulation of AE1 anion exchanger and H(+)-ATPase in rat cortex by acute
      metabolic acidosis and alkalosis.
AB  - The cortical collecting duct (CCD) mediates net secretion or reabsorption of
      protons according to systemic acid/base status. Using indirect
      immunofluorescence, we examined the localization and abundance of the vacuolar
      H(+)-ATPase and the AE1 anion exchanger in intercalated cells (IC) of rat kidney
      connecting segment (CNT) and CCD during acute (6 hr) metabolic (NH4Cl) acidosis
      and respiratory (NaHCO3) alkalosis. AE1 immunostaining intensity quantified by
      confocal microscopy was elevated in metabolic acidosis and substantially reduced
      in metabolic alkalosis. AE1 immunostaining was restricted to Type A IC in all
      conditions, and the fraction of AE1+IC was unchanged in CNT and CCd. Metabolic
      acidosis was accompanied by redistribution of H(+)-ATPase immunostaining towards
      the apical surface of IC, and metabolic alkalosis was accompanied by H(+)-ATPase
      redistribution towards the basal surface of IC. Therefore, acute metabolic
      acidosis produced changes consistent with increased activity of Type A IC and
      decreased activity of Type B IC, whereas acute metabolic alkalosis produced
      changes corresponding to increased activity of Type B IC and decreased activity
      of Type A IC. These data demonstrate that acute systemic acidosis and alkalosis
      modulate the cellular distribution of two key transporters involved in proton
      secretion in the distal nephron.

PMID- 8995727
TI  - Endothelial cells of the kidney vasa recta express the urea transporter HUT11.
AB  - The cell specific expression of the human urea transporter HUT11 in human and rat
      kidneys was investigated by immunochemistry and in situ hybridization. Using
      specific rabbit polyclonal antibodies directed against the N-terminal part and
      the C-terminal part of HUT11, we found that endothelial cells of medullary vasa
      recta (outer and inner medulla) express HUT11. In addition, an HUT11-related
      protein expressed by smooth muscle cells of cortical arterioles can be detected
      by the anti-HUT11 N-terminal peptide antibody but not the anti-HUT11 C-terminal
      peptide antibody. The endothelial expression of HUT11 was confirmed by double
      labeling with anti-CD31 and anti-von Willebrand factor antibodies. No HUT11
      positive cells expressed alpha smooth muscle actin, Tamm Horsfall protein,
      cytokeratin 18, or CAM-L1, a marker of the principal cells of collecting ducts.
      Medullary vasa recta of developing and mature rat kidneys were also stained with
      the anti-HUT11 C-terminal peptide antibody. By in situ hybridization using a
      specific HUT11 35S-cDNA probe on human kidney sections, medullary vasa recta but
      not other renal structures were found to express HUT11 mRNA. We conclude that
      endothelial cells of medullary vasa recta express HUT11, a specific urea
      transporter, which may play a role in urea recycling within the kidney and in the
      mechanisms of urinary concentration and urea excretion.

PMID- 8995728
TI  - Oxidized LDL stimulates the expression of TGF-beta and fibronectin in human
      glomerular epithelial cells.
AB  - Abnormal lipid accumulation in glomeruli is a recognized early event in the
      development of glomerulosclerosis. The presence of LDL and scavenger receptors
      has recently been demonstrated in glomerular cells, including the visceral
      epithelial cells. To explore the possible molecular mechanisms of lipid-induced
      glomerular injury, the present investigation was conducted to examine the effects
      of oxidized LDL (ox-LDL) on the expression of transforming growth factor (TGF)
      beta and fibronectin by cultured human glomerular epithelial cells (GEC).
      Cultured GEC were exposed to human ox-LDL (0 to 100 micrograms/ml) for various
      time points. Ox-LDL induced a dose- and time-dependent increase in the expression
      of TGF-beta mRNA. Actinomycin D, a transcriptional inhibitor, but not
      cycloheximide, a protein synthesis inhibitor, inhibited the response. GEC exposed
      to ox-LDL also demonstrated elevated levels of fibronectin mRNA. In addition,
      treatment of GEC with ox-LDL resulted in increased TGF-beta and fibronectin
      protein expression as detected by immunocytochemistry. Addition of anti-TGF-beta
      antibody significantly inhibited the increase in fibronectin message level
      induced by ox-LDL. These data suggest that ox-LDL stimulates matrix protein
      fibronectin in GEC by a mechanism involving expression of TGF-beta. Thus,
      accumulation of lipids in human glomerular epithelial cells may contribute to the
      pathogenesis of glomerulosclerosis through TGF-beta mediated mechanism(s).

PMID- 8995729
TI  - Monocyte recruitment in cryoglobulinemic membranoproliferative
      glomerulonephritis: a pathogenetic role for monocyte chemotactic peptide-1.
AB  - Monocyte chemotactic peptide-1 (MCP-1) belongs to a large family of cytokines
      known as chemokines. It is a potent mediator of inflammatory response and is
      thought to play a major role in recruiting monocytes into the site of
      inflammation. Mixed cryoglobulinemia is a systemic vasculitis characterized in 10
      to 30% of the cases by renal involvement. Monocyte infiltration into the
      glomerulus, and in the periglomerular and perivascular areas is a common
      histopathological feature of this form of glomerulonephritis. We sought to
      determine, by in situ hybridization and immunohistochemistry, the renal gene and
      protein expression of MCP-1 in cryoglobulinemic glomerulonephritis compared to
      normal kidney, and to correlate it with macrophage infiltration. Kidney biopsy
      specimens were obtained from 9 patients with cryoglobulinemic glomerulonephritis
      and 9 control kidneys. The distribution and intensity of MCP-1 gene and protein
      expression, and the macrophage infiltration (CD68 positive cells) were evaluated
      and quantitated by a computerized image analysis system. In normal kidneys, MCP-1
      was weakly expressed, both at the gene as well as at the protein level. In
      diseased kidneys, a statistically significant (P < 0.001) up-regulation of MCP-1
      gene and protein expression was found, particularly within the areas of
      tubulointerstitial damage and the glomeruli. By means of CD68 positive cells, a
      significant correlation (P < 0.001) was found between glomerular,
      tubulointerstitial macrophage infiltration and MCP-1 expression. Moreover, by
      combining immunohistochemistry and in situ hybridization, we observed the
      presence of CD68 positive cells mainly, if not exclusively, around the cells
      expressing MCP-1 mRNA. Interestingly, a striking increase in MCP-1 urinary
      concentration was found in cryoglobulinemic patients. In conclusion, our data
      suggest that MCP-1 may play a major role in modulating the inflammatory process
      observed in cryoglobulinemic glomerulonephritis.

PMID- 8995731
TI  - Efficient induction of apoptosis in cultured rat glomerular mesangial cells by
      dimeric monoclonal IgA anti-Thy-1 antibodies.
AB  - Apoptosis of glomerular cells (GMC) has been observed in the early phase as well
      as the resolution phase of Thy-1 nephritis. Recently, we and others reported that
      IgG2a (ER4G) and IgG1 (OX7) monoclonal mouse anti-Thy-1 antibodies (anti-Thy-1
      MoAb) are able to induce apoptosis of rat GMC in vivo. The purpose of this study
      was to investigate whether cross-linking of Thy-1 would influence the degree of
      apoptosis in cultured rat GMC using monomeric and dimeric IgA anti-Thy-1 MoAb.
      IgA anti-Thy-1 MoAb (ER4A) was generated by class switching of the IgG producing
      ER4 (ER4G) hybridoma. The ER4A clone spontaneously produces monomeric (m-ER4A)
      and dimeric IgA anti-Thy-1 MoAb *di-ER4A). Unaltered epitope specificity of ER4A
      was confirmed by blocking experiments of the binding of fluorescence labeled ER4G
      to cultured rat GMC with unlabeled ER4A on FACS. For the experiments of
      apoptosis, quiescent rat GMC were incubated for eight hours with medium alone or
      with medium in the presence of 10 micrograms/ml of m-ER4A, di-ER4A or control IgA
      MoAb of corresponding sizes. Apoptosis was assessed by morphological studies,
      agarose gel electrophoresis and quantitative FACS analyses using terminal
      deoxynucleotidyl transferase (TDT) method and the annexin V method. The TDT
      method detects specific-DNA nicking in apoptosis. The annexin V method detects
      early membrane changes during apoptosis. In morphological studies, cells
      incubated with m-ER4A and di-ER4A showed typical apoptotic features such as
      nuclear condensation and fragmentation. DNA isolated from the cells incubated
      with di-ER4A was cleaved into a distinctive ladder pattern compatible with
      apoptosis. In contrast, both medium alone and control IgA MoAb did not reveal
      detectable changes in morphological studies and agarose gel electrophoresis. In
      quantitative analyses by FACS using the TDT method and the annexin method, both m
      ER4A and di-ER4A induced significantly higher percentages of apoptosis in rat GMC
      as compared to the controls. Furthermore, di-ER4A was considerably more efficient
      than m-ER4A in inducing apoptosis possibly through additional cross-linking of
      Thy-1 on the cell surface. This notion was confirmed by experiments, in which the
      addition of goat anti-mouse kappa antibodies enhanced apoptosis of rat GMC pre
      sensitized with m-ER4A. Taken together, our results indicate that apoptosis of
      rat GMC by anti-Thy-1 antibodies is enhanced by cross-linking of Thy-1 on the
      cell surface. These studies are of importance for our understanding of mechanisms
      that may play a role in glomerular diseases.

PMID- 8995730
TI  - Modulation of plasminogen activator inhibitor-1 in vivo: a new mechanism for the
      anti-fibrotic effect of renin-angiotensin inhibition.
AB  - We examined the potential of in vivo linkage of plasminogen activator inhibitor-1
      (PAI-1) and angiotensin II (Ang II) in the setting of endothelial injury and
      sclerosis following radiation injury in the rat. PAI-1 is a major physiological
      inhibitor of the plasminogen activator (PA)/plasmin system, a key regulator of
      fibrinolysis and extracellular matrix (ECM) turnover. PAI-1 mRNA expression in
      the kidney was markedly increased (9-fold) at 12 weeks after irradiation (P <
      1.001 vs. normal control). In situ hybridization revealed significant association
      of PAI-1 expression with sites of glomerular injury (signal intensity in injured
      vs. intact glomeruli, P < 0.001). Angiotensin converting enzyme inhibitors (ACEI,
      captopril or enalapril) or angiotensin II receptor antagonist (AIIRA, L158,809)
      markedly reduced glomerular lesions (thrombosis, mesangiolysis, and sclerosis;
      sclerosis index, 0 to 4+ scale, 0.49 +/- 0.20 in untreated vs. 0.05 +/- 0.02,
      0.02 +/- 0.01, 0.04 +/- 0.02 in captopril, enalapril and AIIRA, respectively, all
      P < 0.01 vs untreated). Further, ACEI and AIIRA markedly attenuated increased PAI
      1 mRNA expression in the irradiated kidney (36, 19 and 20% expression,
      respectively, for captopril, enalapril and AIIRA, compared to untreated
      irradiated kidney, P < 0.05, < 0.01, < 0.01). This effect was selective in that
      neither tissue-type nor urokinase-type PA mRNA expression was affected by these
      interventions. Thus, we speculate that inhibition of the renin-angiotensin system
      may ameliorate injury following radiation by accelerating fibrinolysis and ECM
      degradation, at least in part, via suppression of PAI-1 expression. In summary,
      inhibition of Ang II, in addition to its known effects on vascular sclerosis, may
      also by its novel effect to inhibit PAI-1, lessen fibrosis following
      endothelial/thrombotic injury.

PMID- 8995732
TI  - Immunohistochemical detection of advanced glycosylation end-products in the
      peritoneum and its possible pathophysiological role in CAPD.
AB  - It has recently been suggested that advanced glycosylation end-products (AGEs)
      are formed in the peritoneum in patients on CAPD. However, the exact location of
      AGE accumulation, the relation with the duration of CAPD and its
      pathophysiological role in CAPD remain unclear. If the peritoneum is
      glycosylated, it could bring about altered peritoneal function. Therefore, the
      aim of this study is to clarify the localization of AGEs in the peritoneum in
      accordance with the duration of CAPD and to examine its relation to the
      peritoneal permeability. Fifteen non-diabetic patients were divided into three
      groups (each 5 patients) on the basis of the mean duration (D) of CAPD (Group 1,
      D = 0 month; Group II, D = 34 months; Group III, D = 84 months). The AGE staining
      by monoclonal anti-AGE antibody in the peritoneum and the four-hour peritoneal
      equilibration test (PET) were compared among these groups. AGE was absent or
      found only weakly in Group I. However, in groups II and III, AGE was moderately
      or strongly positive especially in the vascular walls and it was dominant in
      group III. PET revealed that peritoneal permeability for glucose, creatinine,
      beta2-microglobulin and albumin was increased in Group II as compared to Group I,
      and it was further increased in Group III. The results of this study indicate
      that AGEs become dominantly accumulated in the vascular wall in accordance with
      the prolongation of CAPD treatment, and this might play some roles for the
      increased permeability of the peritoneal membrane in CAPD.

PMID- 8995733
TI  - Amyloid beta 2-microglobulin is modified with imidazolone, a novel advanced
      glycation end product, in dialysis-related amyloidosis.
AB  - We have recently demonstrated by immunohistochemistry that amyloid beta 2
      microglobulin (beta 2m) is modified with advanced glycation end products (AGEs)
      in dialysis-related amyloidosis (DRA). To further investigate the role of the
      Maillard reaction in the pathogenesis of DRA, we produced a monoclonal antibody
      to imidazolone, a novel AGE, and a reaction product of arginine and 3
      deoxyglucosone (3-DG) which was accumulated in uremic serum. Then we determined
      the localization of imidazolone in the amyloid tissues by immunohistochemistry
      using the antibody. The connective tissues in carpal tunnel and ligamentum flavum
      were obtained from six patients with carpal tunnel syndrome and two patients with
      destructive spondyloarthropathy. Imidazolone was localized to all the beta 2m
      positive amyloid deposits in these patients. Western blotting using the antibody
      demonstrated that beta 2m extracted from the synovium amyloid of hemodialysis
      patients was modified with imidazolone. Further, beta 2m isolated from the blood
      ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In
      vitro incubation of beta 2m with 3-DG produced imidazolone-modified beta 2m. In
      conclusion, amyloid tissue beta2m is modified with imidazolone in patients with
      DRA. 3-DG accumulating in uremic serum may be involved in the modification of
      beta 2m with imidazolone.

PMID- 8995734
TI  - Altered expression of fibrogenic growth factors in IgA nephropathy and focal and
      segmental glomerulosclerosis.
AB  - The profile of fibrogenic growth factor expression was assessed in biopsies from
      27 patients with IgA nephropathy (IgAN), 14 focal and segmental glomerulsclerosis
      (FSGS) patients and 8 controls, by immunohistochemistry. Increased platelet
      derived growth factor (PDGF)-A and PDGF-B expression was detected in glomeruli
      and in vascular structures and collapsed tubules in the interstitium. Computer
      assisted image analysis demonstrated increased glomerular PDGF-A in IgAN (P <
      0.05), but not FSGS patients, compared to controls, suggesting an association
      with mesangial proliferation. PDGF receptors were prominent in areas of mesangial
      expansion and intertubular fibrosis. Significant increases in interstitial PDGF
      Receptor beta (PDGFR-beta) were detected for both IgAN (P < 0.01) and FSGS (P <
      0.05) patients. Interstitial PDGFR-beta expression was significantly correlated
      to monocyte/macrophage infiltrate (P < 0.0001). Increased basic fibroblast growth
      factor (bFGF) expression was observed segmentally in glomeruli, and in areas of
      tubulointerstitial damage. Higher proportions of patients with FSGS than IgAN had
      elevated interstitial bFGF (P < 0.005) and PDGF, reflecting the more severe
      degree of vascular and tubulointerstitial injury in FSGS patients. This study
      demonstrates distinct patterns of fibrinogenic growth factors in IgAN and FSGS,
      strongly associated with the severity and type of injury.

PMID- 8995735
TI  - Human peritoneal fibroblast proliferation in 3-dimensional culture: modulation by
      cytokines, growth factors and peritoneal dialysis effluent.
AB  - Structural and functional alterations of the peritoneal membrane are a
      significant problem in long-term peritoneal dialysis patients. The present study
      has established a 3-dimensional (3D) cell culture system to study the human
      peritoneal fibroblast (HPFB) and to examine its proliferative responses to
      cytokines and growth factors as well as dialysis effluent obtained from patients
      during peritoneal infection. PDGF-AB, basic FGF and IL-1 beta induced a time and
      dose dependent increase in 3D-HPFB proliferation. At day 9 proliferation, as
      assessed by MTT uptake, was increased by 2.4-, 2.3- and 1.5-fold above control by
      PDGF-AB (50 ng/ml), bFGF (50 ng/ml) and IL-1 beta (10 ng/ml), respectively (N =
      5, P = 0.04 for all). These effects could be inhibited by co-incubation with anti
      PDGF-AB antibody, anti-bFGF or IL-1ra, respectively. Exposure of 3D-HPFB to TGF
      beta 1 did not result in an increase in cell proliferation. Incubation of 3D-HPFB
      with peritoneal macrophage (PMo) or human peritoneal mesothelial cell (HPMC)
      conditioned medium also resulted in a time and dose dependent increase in
      proliferation. At day 9, proliferation was maximally increase 1.65- and 1.92-fold
      by peritoneal macrophage- and mesothelial cell-conditioned medium, respectively.
      Cell free PDE, obtained from CAPD patients during episodes of peritonitis,
      induced 3D-HPFB proliferation above control values (2- to 6.5-fold increases, N =
      5, P < 0.05 for all). This mitogenic potential of PDE was reduced following
      dilution, and with time following peritonitis there was a gradual decrease in the
      mitogenic effect of PDE. The proliferative potential of PDE was significantly
      reduced following co-incubation with IL-1ra (45.7% inhibition), anti-bFGF (34.9%
      inhibition) and anti PDGF-AB (27.4% inhibition). These data indicate that
      infected PDE causes fibroblast hyperplasia which might potentially contribute to
      pro-fibrotic processes during CAPD.

PMID- 8995736
TI  - Effect of chronic metabolic acidosis on the growth hormone/IGF-1 endocrine axis:
      new cause of growth hormone insensitivity in humans.
AB  - The effects of metabolic acidosis on growth hormone and IGF-1 are poorly
      understood. We investigated the effects of chronic metabolic acidosis (induced by
      administration on NH4Cl, 4.2 mmol/kg body wt/day) on the growth hormone/IGF-1
      endocrine axis in 6 normal male volunteers during metabolic balance conditions.
      NH4Cl administration resulted in hyperchloremic metabolic acidosis with plasma
      bicarbonate decreasing from 25 +/- 0.4 to 15.5 +/- 0.9 mmol/liter (P < 0.001).
      Metabolic acidosis significantly decreased serum IGF-1 concentration from 45 +/-
      6 to 33 +/- 6 nmol/liter (P = 0.002), while serum IGF binding protein 3
      concentration was not affected significantly. The growth hormone response to
      growth hormone releasing factor administration (1 microgram per kg body wt,
      intravenous bolus) was enhanced significantly during acidosis. The IGF-1 response
      to growth hormone administration (0.1 U kg body wt subcutaneously, every 12 hr
      for 48 hr) was blunted significantly during acidosis. Apparent endogenous serum
      half-life and metabolic clearance rates of growth hormone were not altered
      significantly by acidosis. Metabolic acidosis in humans results in a significant
      decrease in serum IGF-1 concentration without a demonstrable effect on IGF
      binding protein 3, and is related to a resistance to the hepatocellular action of
      growth hormone. The primary defect in the growth hormone/IGF-1 axis occurs via an
      impaired IGF-1 response to circulating growth hormone with consequent diminution
      of normal negative feedback inhibition of IGF-1 on growth hormone, as evidenced
      by the exaggerated growth hormone response to growth hormone releasing factor
      administration.

PMID- 8995737
TI  - Susceptibility to anti-glomerular basement membrane disease is strongly
      associated with HLA-DRB1 genes.
AB  - Anti-glomerular basement membrane (anti-GBM) disease is caused by autoimmunity to
      a component of glomerular basement membrane. The major autoantigen has been
      identified as the NC1 domain of the alpha 3 chain of type IV collagen, and
      patients are characterized by the presence of specific autoantibodies to this
      molecule. In common with other autoimmune disorders, there is a strong
      association with HLA genes, with up to 80% of patients inheriting an HLA-DR2
      haplotype. To examine the genetic basis of susceptibility to anti-GBM disease in
      more detail, the HLA-DRB and DQB alleles inherited by 82 patients were analyzed
      using sequence specific oligonucleotides. This identified a hierachy of
      association of DRB1 genes with anti-GBM disease, including susceptibility
      (DRB1*15, DRB1*04), neutral (DRB1*03) and protective (DRB1*07) alleles. Analysis
      of inherited haplotypes, particularly DRB1*04 and DRB1*07 carrying haplotypes,
      provided further evidence that the primary association was with genes at the DRB1
      locus. Comparison of the sequences of the positively and negatively associated
      alleles showed that polymorphic residues in the second peptide binding region of
      the HLA Class II antigen binding groove segregated with disease. This work
      supports the hypothesis that the HLA associations in anti-GBM disease reflect the
      ability of certain Class II molecules to bind and present peptides derived from
      the autoantigen to T helper cells.

PMID- 8995738
TI  - Age-related glomerulosclerosis and interstitial fibrosis in Milan normotensive
      rats: a podocyte disease.
AB  - In Milan normotensive (MNS) rats glomerulosclerosis and interstitial fibrosis
      develop spontaneously in the absence of hypertension. Renal changes were
      sequentially assessed in these rats between 2 and 10 months of age. At 10 months,
      rats were characterized by heavy proteinuria, increased serum creatinine, focal
      or global glomerulosclerosis in 51 +/- 12% of the glomeruli as well as
      tubulointerstitial injury involving > 25% of the section area. Cell injury in
      podocytes (evidenced as increased expression of desmin and by electron
      microscopy) and interstitial fibroblasts (increased expression of alpha-smooth
      muscle actin) and mild glomerular hypertrophy were witnessed as early as three to
      four months of age and preceded glomerulosclerosis and interstitial fibrosis.
      Only minor evidence of mesangial cell activation (as assessed by glomerular (de
      novo alpha-smooth muscle actin or type I collagen expression or increased cell
      proliferation) was noted throughout the observation period. Later stages of the
      disease were characterized by glomerular and/or tubulointerstitial macrophage
      influx and osteopontin expression (a chemoattractant), mild accumulation of
      lymphocytes, platelets, fibrinogen, as well as by a progressive accumulation of
      various matrix proteins. Progressive renal disease in MNS rats is thus noteworthy
      for the relative lack of mesangial cell activation. Rather, early podocyte
      damage, induced by yet unknown mechanisms, may underlie the development of
      glomerulosclerosis and subsequent interstitial fibrosis.

PMID- 8995740
TI  - Effect of HDL and atherogenic lipoproteins on formation of O2- and renin release
      in juxtaglomerular cells.
AB  - Atherogenic lipoproteins and reactive oxygen species stimulate renin release from
      isolated juxtaglomerular (JG) cells. Here we assessed whether stimulation of
      renin release is mediated by formation of superoxide anion (O2-), and whether the
      effects of oxidized lipoproteins, like in many other biological systems, can be
      prevented by the antiatherogenic high density lipoprotein (HDL). Lipoproteins
      were prepared from human plasma, and JG cells from mouse and rat kidneys. Basal
      renal activity of JG cells was measured in culture supernatants and cells, and
      was dose-dependently and significantly stimulated by oxidized LDL (50 and 300
      micrograms/ml) and by oxidized Lp(a) (1, 10 and 30 micrograms/ml). Administration
      of HDL alone had no effect on renin release. However, coincubation with 100
      micrograms/ml HDL significantly suppressed oxidized LDL- and oxidized Lp(a)
      stimulated renin release. O2- production of JG cells was directly measured using
      a chemiluminescence assay. Stimulation with 10 micrograms/ml oxidized LDL and
      oxidized Lp(a) significantly increased the O2- generation of JG cells. In the
      presence of 5 micrograms/mL HDL, O2- production was reduced to control levels.
      These data indicate that stimulation of JG cells with oxidized LDL and Lp(a)
      induces formation of O2-, which may stimulate renin release in an autocrine
      fashion. Renin release can be prevented by HDL, presumably by preventing the
      formation of O2-.

PMID- 8995739
TI  - Accuracy of the diagnosis of hypertensive nephrosclerosis in African Americans: a
      report from the African American Study of Kidney Disease (AASK) Trial. AASK Pilot
      Study Investigators.
AB  - African Americans have excess hypertension and end-stage renal disease presumed
      due to hypertension compared to Caucasians. The AASK was designed to examine the
      impact of antihypertensive therapies and two levels of blood pressure control on
      the rate of decline of GFR in African Americans with presumed hypertensive renal
      disease. During the pilot phase of the trial, eligible participants were
      requested to undergo renal biopsy to assess the underlying lesions in this
      population. Eighty-eight hypertensive (diastolic BP > 95 mm Hg) non-diabetic
      African American patients between the ages of 18 to 70 years, with GFR between 25
      to 70 ml/min/1.73 m2 and without marked proteinuria were assessed for possible
      renal biopsy. Forty-three patients did not undergo renal biopsy due to refusal or
      contraindications. Adequate renal biopsies were obtained in 39 of the remaining
      46 patients. Biopsy findings were analyzed and then compared to clinical
      parameters. The 39 patients studied, 29 men and 10 women, were on average 53.0 +/
      11.0 years old, and had a MAP of 109 +/- 15 mm Hg and GFR 51.7 +/- 13.6
      ml/min/1.73 m2 (not significantly different from nonbiopsied patients). Thirty
      eight of these 39 biopsies showed arteriosclerosis and/or arteriolosclerosis,
      severity on average 1.5 +/- 0.9 and 1.5 +/- 0.8, respectively on a 0 to 3+ scale.
      Interstitial fibrosis was moderate, 1.3 +/- 0.9 (0 to 3+ scale). Segmental
      glomerulosclerosis was present in five biopsies, and in one patient, biopsy and
      clinical findings were consistent with idiopathic focal segmental
      glomerulosclerosis. Additional lesions included mesangiopathic glomerulonephritis
      in one patient, basement membrane thickening suggestive of diabetic nephropathy
      in one, and cholesterol emboli in two cases. Arteriolar and arterial sclerosis
      were tightly linked, and correlated with interstitial fibrosis and the reciprocal
      of serum creatinine. Global glomerulosclerosis was extensive, involving on
      average 43 +/- 26% of glomeruli. The extent of this lesion did not correlate with
      degree of arteriolar or arterial thickening, but did correlate with systolic
      blood pressure (P = 0.0174), the reciprocal of serum creatinine (P = 0.0009),
      serum cholesterol (P = 0.0129) and interstitial fibrosis (P < 0.0001). These data
      underscore that renal biopsies in non-diabetic hypertensive African-Americans
      with mild to moderate renal insufficiency in the absence of marked proteinuria
      are overwhelmingly likely to show renal vascular lesions consistent with the
      clinical diagnosis of hypertensive nephrosclerosis.

PMID- 8995742
TI  - IgG subclasses in patients with membranoproliferative glomerulonephritis,
      membranous nephropathy, and lupus nephritis.
AB  - Primary glomerulopathy can be classified into seven essential patterns based on
      histopathological studies. The pathogenesis of membranoproliferative
      glomerulonephritis (MPGN), and membranous nephropathy (MN), which show glomerular
      IgG deposition and induce mainly nephrotic syndrome, is not known. To clarify the
      role of IgG subclass in glomerulonephritis, we compared serum concentrations of
      IgG subclasses, the ratio of serum IgG subclasses to total IgG (%IgG subclass),
      and glomerular deposition of IgG subclasses between 7 MPGN patients, 21 MN
      patients, and 9 lupus nephritis (LN) patients. Serum IgG subclasses and %IgG in
      all groups were almost within normal range based on the values in Japanese
      healthy adults. In the MPGN and MN groups, the IgG1 concentration was significant
      lower than that of the LN group (P < 0.001, P < 0.0001, respectively). The IgG2
      concentration in the MPGN group decreased significantly compared with that in the
      LN group (P < 0.05). The %IgG2 of the LN group decreased significantly compared
      with that of the MN group (P < 0.05). The %IgG3 of the MPGN group was
      significantly higher that that of the MN group (P < 0.05). The glomerular
      immunofluorescent intensity of IgG1 and IgG2 were significantly stronger in the
      LN group than in the MPGN and MN groups (IgG1, P < 0.001, P < 0.01, respectively;
      IgG2, P < 0.0001, P < 0.0001, respectively). IgG3 in the MPGN and LN groups
      deposited significantly compared with that in the MN group (P < 0.0001, P < 0.01,
      respectively). The intensity of IgG4 in the MN group showed a significant
      difference compared with that in the MPGN and LN groups (P < 0.0001, P < 0.01,
      respectively). IgG3 is an important factor in the pathogenesis of primary MPGN,
      while IgG4 relates to glomerular IgG deposition in MN.

PMID- 8995741
TI  - Molecular genetic identification of families with juvenile nephronophthisis type
      1: rate of progression to renal failure. APN Study Group. Arbeitsgemeinschaft fur
      Padiatrische Nephrologie.
AB  - Familial juvenile nephronophthisis (NPH), an autosomal recessive cystic disease
      of the kidney, is the most common genetic cause of end-stage renal disease (ESRD)
      in the first two decades of life. A gene locus for nephronophthisis type 1 (NPH1)
      has been mapped by linkage analysis to chromosome 2q13. We performed a haplotype
      analysis in 16 NPH families with at least two affected patients with the typical
      history, clinical signs and histology of NPH using microsatellite markers of the
      NPH1 genetic region. By demonstration of a recombinant event marker D2S1893 was
      identified as a novel centromeric flanking marker to the NPH1 critical genetic
      region. Absence of linkage to the NPH1 locus in six NPH families confirmed the
      existence of at least one additional gene locus for NPH. Linkage to the NPH1
      locus was demonstrated in 10 families. In 8 of these families a homozygous
      deletion was identified. These data permit for the first time the study of the
      development of renal failure in a subset of NPH1 families, which is most likely
      homogeneous with regard to the responsible gene locus. We present a statistical
      description of serial serum creatinine measurements in NPH1. Analysis of renal
      death revealed a median of 13.1 years. Age-dependent quartiles were generated for
      serum creatinine. In summary, the new marker provides a diagnostic tool to aid in
      the diagnosis of NPH, while the progression charts offer a standard for an
      assessment of the rate of progression to ESRD for patients with NPH1 to be used
      in future therapeutic trials and for a prediction of the individual course of the
      disease.

PMID- 8995743
TI  - Stenting of central venous stenoses in hemodialysis patients: long-term results.
AB  - From November 1992 through July 1996, 15 Wallstents were implanted for the
      treatment of symptomatic central arm vein obstructions in 14 hemodialysis
      patients (10 subclavian, 2 brachiocephalic vein stenoses, 2 subclavian vein
      occlusions). There were no acute complications. All patients were investigated by
      clinical examination and color-duplex sonography at regular three month
      intervals. When recurrent swelling predicted restenosis, phlebography was also
      performed. During the follow-up, high grade stenoses at the central or peripheral
      ends of four stents were successfully treated with five overlapping stents,
      giving a total of 20 Wallstent implantations. Complete occlusion of another
      subclavian vein distally to the stent at 16 months required ligation of the
      patient's arteriovenous fistula. Life table analysis including all 20 stents
      revealed a cumulative primary one year (two year) stent patency of 70% (50%). The
      cumulative secondary one year (two year) stent patency was 100% (85%). We believe
      that in hemodialysis patients, PTA plus Wallstent implantation is a safe and
      effective procedure in the treatment of central venous stenoses and even shorter
      occlusions. Consequent follow-up allows for timely diagnosis and treatment of
      restenoses, thus guaranteeing long-term patency rates comparable to those of veno
      venous bypass surgery.

PMID- 8995744
TI  - Receptors for natriuretic peptides in a human cortical collecting duct cell line.
AB  - The aim of the present study was to analyze the expression of natriuretic peptide
      receptors in human collecting duct, by using a newly established SV40 cell line
      (HCD). ANP and C-type natriuretic peptide (CNP) induced a concentration-dependent
      increase in cGMP suggesting the presence of type-A (NPR-A) and type-B (NPR-B)
      receptors, respectively. Threshold concentrations were 1 pM and 1 nM,
      respectively, and stimulated over basal cGMP ratios were 500 and 160 at 0.1
      microM ANP and CNP. The urodilatin concentration-response curve was similar to
      that of ANP. [125I]-ANP bound specifically to HCD cells in a time-dependent
      fashion, reaching a plateau-phase between one and two hours at 4 degrees C.
      Equilibrium saturation binding curves suggested a single group of receptor sites
      (Kd = 421 +/- 55 pM, Bmax = 49.2 +/- 8.8 fmol/mg protein, Hill coefficient = 1.44
      +/- 0.1, N = 6). Binding of [125I]-ANP was not displaced by CNP or by C-ANP (4
      23), a specific ligand of clearance receptors (NPR-C), and thus occurred mainly
      via NPR-A. Neither Northern blot analysis nor RT-PCR could detect NPR-C mRNA,
      although the latter was clearly identified in control human glomerular visceral
      epithelial cells. In contrast, PCR products with the expected lengths were
      obtained for NPR-A and NPR-B. In conclusion, HCD cells express both NPR-A and NPR
      B, as demonstrated by mRNA and cGMP production studies, but fail to produce NPR
      C. This suggests that the human cortical collecting duct is a target for ANP, CNP
      and urodilatin.

PMID- 8995745
TI  - Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral
      endopeptidase enzymuria.
AB  - Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush
      border, physiologically released into the urine with apical membrane fragments.
      As proximal tubular atrophy was a histological hallmark of Chinese herbs
      nephropathy (CHN), this study firstly determined renal excretion of NEP in
      healthy control subjects (N = 31), in patients with CHN (N = 26) and in women
      having consumed Chinese herbs and whose renal function was normal but running the
      risk of developing CHN (N = 27). Another patient group consisted of female
      patients with glomerular diseases (N = 12). At the same time, measurements of
      urinary microproteins (Clara cell protein, retinol binding protein, beta 2
      microglobulin and alpha 1-microglobulin) were performed, as indicators of tubular
      dysfunction. Cell damage was estimated by the excretion of N-acetyl-beta-D
      glucosaminidase (NAG). In the control group, the physiological NEP enzymuria was
      43.1 micrograms/24 hr (geometric mean). In CHN patients, levels of urinary NEP
      were significantly decreased in those with moderate renal failure (26.7
      micrograms/24 hr; N = 21; P < 0.05) and almost abolished in end-stage renal
      failure patients (4.35 micrograms/24 hr; N = 5; P < 0.05). In patients at risk as
      well as in patients with glomerular diseases, urinary NEP levels were not
      statistically different from those observed in control subjects (40.68
      micrograms/24 hr and 48.5 micrograms/24 hr, respectively). Several degrees of
      tubular dysfunction and injury were noted in patients groups, as attested by
      increased urinary microproteins and NAG excretions. Considering the data from
      control and CHN patients, NEP enzymuria positively correlated with individual
      creatinine clearance values (r = 0.76; P = 0.0001) and negatively correlated with
      urinary microproteins levels (r = -0.55; P = 0.00001). Finally, NEP was regularly
      quantitated in the urine of 6 CHN patients for a period ranging from six months
      to two years and in 19 patients at risk during two years, respectively. In the
      first group, renal function progressively deteriorated in 3 patients, leading
      them to renal replacement therapy after 38 to 115 weeks. Stable parameters were
      observed in the remaining 3 patients. A direct correlation between creatinine
      clearance and NEP excretion was found longitudinally in each case. In the second
      group, no significant change of urinary NEP levels was observed (45.9
      micrograms/24 hr), in parallel with stable renal function. Taken together, these
      results indicate that, in CHN patients, NEP enzymuria provides a rapid and
      noninvasive determination of the degree of structural impairment affecting the
      proximal tubular population and further reflecting the severity of the renal
      disease. The interest of this urinary marker in monitoring the progression of
      other tubulointerstitial diseases remains to be assessed.

PMID- 8995746
TI  - Nitric oxide release in the peripheral blood during hemodialysis.
AB  - These studies evaluated the nitric oxide (NO) release in peripheral blood during
      a four-hour hemodialysis (HD) with single-used cuprophane (CU), polysulfone (PS)
      and polyacrylonitrile (PAN) membranes in 10 chronic uremic patients. Continuous
      monitoring of blood NO concentrations was performed with a sterile NO sensor
      probe inserted vertically into the arterial blood line between the arteriovenous
      fistula and dialyzer. In the initial period of HD two peaks of blood NO
      concentrations were observed: the first occurred at the very start of HD and
      lasted approximately one minute, and the second peaked to a lesser extent at 20
      to 26 minutes after the initiation of HD. The extent of NO release was dependent
      on the type of dialysis membrane used. Areas under curves for blood NO
      concentrations (in mumol x min) were as follows: CU, 450.8 +/- 163.3; PS, 247.3
      +/- 150.6*; PAN, 200.4 +/- 91.0* (*P < 0.05 vs. CU). During the first hour of HD
      (N = 6) blood NO concentrations were significantly higher at the outlet of CU
      dialyzer than those found at the inlet. The areas under their curves (in mumol x
      min) were 169.1 +/- 1.9 and 107.5 +/- 1.6, respectively (P < 0.001). Areas under
      curves for blood NO concentrations measured for five minutes following a five
      minute in vitro incubation of 5 ml heparinized uremic blood samples (N = 10) with
      dialysis membranes (50 cm2) were as follows (in nmol x min): CU, 2380 +/- 289*;
      PS, 1293 +/- 45*; PAN, 1117 +/- 37*; control, 502 +/- 56 (*P < 0.05 vs. control).
      The addition of sodium heparin to uremic blood platelet suspension induced an
      immediate rise in NO release in a dose-dependent manner, which proved to be a
      hyperbolic relationship. During HD with CU (N = 6), PS (N = 6) and PAN (N = 6)
      membranes blood plasma cGMP concentrations significantly increased, particularly
      at 20 and 60 minutes of the procedure. No significant differences in blood plasma
      cGMP levels were found between individual dialysis membranes, and no significant
      correlations were observed between blood plasma cGMP levels and blood NO
      concentrations. The results indicate that during HD NO is released in the
      peripheral blood due to blood-membrane and heparin-blood platelet interactions.
      The extent of intradialytic NO release is dependent on the type of dialysis
      membrane used (CU > PS approximately PAN).

PMID- 8995748
TI  - Early protocol renal allograft biopsies and graft outcome.
AB  - To evaluate whether biopsies performed early after transplantation in stable
      grafts can predict graft failure due to chronic transplant nephropathy, a
      protocol biopsy was performed at three months in 98 patients treated with
      antilymphocytic antibodies, cyclosporine and prednisone. Patients were followed
      for 58 +/- 16 months. Histological diagnosis according to the Banff schema were:
      normal (N = 41), borderline changes (N = 12), chronic transplant nephropathy
      (CTN; N = 30), CTN associated to borderline changes (N = 11) and acute rejection
      (N = 4). Biopsies displaying acute rejection were not considered for statistical
      analysis. Since clinical characteristics of patients displaying CTN either with
      or without tubulitis were not different, biopsies were grouped as presence or
      absence of CTN. Patients displaying CTN had an increased incidence of acute
      rejection before performing biopsy (24.3 vs. 3.9%, P = 0.003), a higher mean
      cyclosporine level until biopsy (242 +/- 74 vs. 214 +/- 59 ng/ml, P = 0.049) and
      a lower actuarial graft survival (80.5% vs. 94.4%, P = 0.024). We conclude that
      early protocol biopsies are useful to detect patients at risk of losing their
      graft due to chronic transplant nephropathy.

PMID- 8995747
TI  - Changes in glomerular epithelial cells induced by FGF2 and FGF2 neutralizing
      antibody in puromycin aminonucleoside nephropathy.
AB  - In the present study, two series of experiments were done with PAN nephropathy
      rats given fibroblast growth factor 2 (FGF2) or FGF2 neutralizing antibodies. In
      the first series of experiments, a dose of 10 micrograms of FGF2 (FGF2 group), 40
      micrograms of an FGF2 neutralizing antibody (Anti-FGF2 group) or an equal volume
      of physiological saline (Control group) was administered for four days after PAN
      injection. Urinary protein increased more in the FGF2 group than in the other two
      groups. PCNA (+) glomerular cells were found in decreasing order in groups FGF2,
      Control and Anti-FGF2. Most of the PCNA (+) cells were podocytes and epithelial
      cells of Bowman's capsule. Staining for desmin, a marker of podocyte injury, was
      significantly reduced in the Anti-FGF2 group. Glomerular adhesive lesions were
      found in decreasing order in groups FGF2, Control and Anti-FGF2. The second
      series of experiments was designed to study the effects of FGF2 neutralizing
      antibody (40 micrograms for 5 days after PAN injection, in MoAb group) on
      severely damaged podocytes caused by repeated (two courses) injections in the PAN
      nephropathy rats. The results were the same as those in series 1. An increase in
      urinary protein excretion was observed in both groups, but on the 40th day, the
      level of proteinuria in the MoAb group decreased abruptly. It was observed that
      the MoAb group had few adhesive glomeruli compared to the IgG group
      (administration of mouse IgG) and the PCNA (+) epithelial cells of Bowman's
      capsule were also few. It was supposed that FGF2 would promote the formation of
      adhesive lesions by stimulating the proliferation of podocytes and epithelial
      cells of Bowman's capsule. Additionally, FGF2 itself was thought to impair
      podocytes because of the increasing desmin score and proteinuria.

PMID- 8995749
TI  - Effective suppression of parathyroid hormone by 1 alpha-hydroxy-vitamin D2 in
      hemodialysis patients with moderate to severe secondary hyperparathyroidism.
AB  - Calcitriol, as used for treating secondary hyperparathyroidism, has a low
      therapeutic index. The safety and efficacy of the vitamin D analog, 1 alpha (OH)
      vitamin D2, (1 alpha D2), which has less toxicity in animals than 1 alpha (OH)
      vitamin D3, was tested in a multicenter study of 24 hemodialysis patients with
      secondary hyperparathyroidism [serum intact (i) PTH > 400 pg/ml]. Calcium-based
      phosphate binders alone were used to maintain serum phosphorus < or = 6.9 mg/dl.
      After eight weeks without calcitriol (washout), oral 1 alpha D2, 4 micrograms/day
      or 4 micrograms thrice weekly, was started, with the dose adjusted over 12 weeks
      to maintain serum iPTH between 130 and 250 pg/ml. Pre-treatment serum iPTH fell
      from 672 +/- 70 pg/ml (SEM) to 289 +/- 36 after treatment (P < 0.05). The maximal
      decrease in serum iPTH was 48 to 96%, with 87.5% of patients reaching target iPTH
      levels. The final dose of 1 alpha D2 average 14.2 micrograms/week. Pre-treatment
      serum calcium rose modestly from 8.8 +/- 0.2 mg/dl to 9.5 +/0 0.2 after treatment
      (P < 0.001). Only once did modest hypercalcemia (serum Ca > 11.2 mg/dl)
      necessitate stopping treatment. Neither the average serum P level, the incidence
      of hyperphosphatemia, nor the dose of phosphate binders changed from washout to
      treatment. Thus, oral 1 alpha D2 is highly efficacious in suppressing secondary
      hyperparathyroidism in hemodialysis patients and is safe despite exclusive use of
      calcium-based phosphate-binders. Future studies should clarify the optimal dosage
      regimen.

PMID- 8995750
TI  - Sources of human urinary epinephrine.
AB  - The kidney is a likely source for some urinary epinephrine (E) since
      adrenalectomized animals and humans continue to excrete urinary E and the human
      kidney contains E synthesizing enzymes. We studied subjects during an intravenous
      infusion of 3H-E to determine the fraction of urinary E derived from the kidney.
      Eight normal subjects (CON) and 5 older, heavier hypertensives (OHH) ate a light
      breakfast along with ascorbic acid supplementation and had intravenous and
      arterial lines placed. They received an infusion of 3H-E and had an oral water
      load. During the final hour of 3H-E infusion, urine and arterial blood samples
      were collected for 3H-E and E levels. After the 3H-E infusion was abruptly
      discontinued, arterial blood samples were collected to measure 3H-E kinetics. The
      total body clearance of 3H-E was about 2,500 ml/min from plasma and clearance of
      3H-E to urine was about 170 ml/min. CON had plasma E levels of 43 +/- 4 pg/ml.
      Their predicted rate of clearance of E from plasma to urine of 7,471 +/- 865
      pg/min was less than (P = 0.018) the actual urinary E excretion of 15,037 +/-
      2,625 pg/min. Thus, 43 +/- 9% of urinary E in CON was apparently derived from
      renal sources and not filtered from blood. Among OHH 85 +/- 4% of urinary E was
      derived from the kidney, significantly (P < 0.01) different from CON. The OHH
      also produced much more urinary E than predicted from plasma 3H-E clearance into
      urine (P = 0.03). A major fraction of urinary E is not filtered from the blood
      stream but is apparently derived from kidney. A small fraction of urinary E may
      be derived from E stored in nerve endings along with norepinephrine, but this
      probably represents less than 2% of urinary E. Renal cleavage of E sulfate into E
      may be another potential source of urinary E. Some, and perhaps most, urinary E
      not filtered from the bloodstream is derived from renal N-methylation of
      norepinephrine as the human kidney has two enzymes capable of converting
      norepinephrine to E. In conclusion, a major portion of urinary E is derived from
      the kidney and not filtered from the bloodstream. This is an important factor in
      the interpretation of urine E levels. Renal E could alter renal blood flow,
      electrolyte reabsorption, and renin release prior to excretion into urine.

PMID- 8995751
TI  - Depressed expression of calcium receptor in parathyroid gland tissue of patients
      with hyperparathyroidism.
AB  - The factors involved in abnormal parathyroid cell secretory function and growth
      in patients with primary (I degree) and secondary (II degree) hyperparathyroidism
      are still incompletely understood. We compared the expression of the calcium
      sensing receptor (CaR) at the gene message and the protein level in parathyroid
      tissue obtained from patients with I degree non-uremic or II degree uremic
      hyperparathyroidism with that in normal parathyroid tissue, using in situ
      hybridization and immunohistochemistry techniques. The expression of the CaR mRNA
      and protein was reduced in most cases of I degree adenoma and II degree
      hyperplasia, compared with strong expression normal parathyroid tissue. In II
      degree hyperparathyroidism, expression of both receptor mRNA message and protein
      was often particularly depressed in nodular areas, compared with adjacent non
      nodular hyperplasia. Decreased Ca-R expression in adenomatous and hyperplastic
      parathyroid glands would be compatible with a less efficient control of PTH
      synthesis and secretion by plasma calcium than in normal parathyroid tissue.

PMID- 8995752
TI  - Hyperosmolality suppresses but TGF beta 1 increases MMP9 in human peritoneal
      mesothelial cells.
AB  - Peritoneal mesothelial cells are directly exposed to hyperosmolar dialysates
      which may enhance extracellular matrix accumulation and hence compromise
      ultrafiltration. Because these cells are laid on a type IV collagen containing
      basement membrane, we examined the pattern of type IV collagenases produced by
      cultured human mesothelial cells and their regulation by hyperosmolality and TGF
      beta 1. A cell line (HMrSV5) exhibiting major features of normal peritoneal
      mesothelial cells was derived from a primary culture retrovirally transduced with
      SV40 large-T antigen. Zymography and Western blot analysis showed that: (i) human
      peritoneal mesothelial cells produced and excreted MMP2 and MMP9 and their
      inhibitors TIMP1 and TIMP2; (ii) hyperosmolality drastically reduced the
      expression of MMP9 irrespective of the osmolyte used in a time- and concentration
      dependent manner; (iii) TGF beta 1 unexpectedly increased MMP9 activity and
      protein in exponentially growing cells and could restore MMP9 activity suppressed
      by hyperosmolality in confluent cultures. To exclude a specific effect of SV40
      large-T antigen on matrix metalloproteinases production and regulation, these
      results were confirmed in primary cultures derived from visceral peritoneal
      samples from different donors. Therefore, the hyperosmolality of dialysates may
      favor an accumulation of type IV collagen and thickening of peritoneal basement
      membrane, while TGF beta 1 released during infections may induce the degradation
      of type IV collagen and its replacement by interstitial collagens.

PMID- 8995753
TI  - Hepatitis G virus infection in hemodialysis patients.
AB  - The increased risk of hemodialysis patients for infections sustained by hepatitis
      viruses is likely to extend to a newly discovered parenterally transmitted virus,
      HGBV-C/HGV, able to cause acute and chronic hepatitis. The aim of this study was
      to assess the prevalence and clinical relevance of this infection in Italian
      hemodialysis patients. Nineteen of 100 patients (19%) on maintenance hemodialysis
      were viremic for HGBV-C/HGV, and all of them were infected with a HGV-like
      genotype. Eight of these patients were coinfected by hepatitis B or hepatitis C
      viruses. A clinical picture of chronic hepatitis was not appreciable in patients
      with isolated HGV infection and the presence of HGV did not appear to modify the
      clinical course of hepatitis B and hepatitis C infections.

PMID- 8995754
TI  - Complications of polycystic kidney disease.

PMID- 8995755
TI  - Megencephaly: a new mouse mutation on chromosome 6 that causes hypertrophy of the
      brain.
AB  - Megencephaly, enlarged brain, occurs in several acquired and inherited human
      diseases including Sotos syndrome, Robinow syndrome, Canavan's disease, and
      Alexander disease. This defect can be distinguished from macrocephaly, an
      enlarged head, which usually occurs as a consequence of congenital hydrocephalus.
      The pathology of megencephaly in humans has not been well defined, nor has the
      defect been reported to occur spontaneously in any other species. In this report
      we describe a recessive mutation in the mouse that results in a 25% increase in
      brain size in the first 8 months of life. We have determined that the
      megencephaly is characterized by overall hypertrophy of the brain, and not by
      hyperplasia of particular cell types or by hypertrophy of a singular tissue
      compartment. Edema and hydrocephalus are absent. This mutation has been mapped to
      mid-distal mouse Chromosome (Chr) 6 in a region homologous with human Chr 12.

PMID- 8995756
TI  - Characterization and localization of the mProx1 gene directly upstream of the
      mouse alpha-globin gene cluster: identification of a polymorphic direct repeat in
      the 5'UTR.
AB  - The alpha-globin major regulatory element (alpha MRE) positioned far upstream of
      the gene cluster is essential for the proper expression of the alpha-globin
      genes. Analysis of the human and mouse alpha-globin Upstream Flanking Regions
      (alpha UFR) has identified three nonglobin genes in the order Dist1-MPG-Prox1
      alpha-globin. Further characterization of the whole region indicates that the
      alpha MRE and several other erythroid DNase HSSs are associated with the
      transcription unit of the Prox1 gene. In this paper we describe the
      characterization and localization of the mouse Prox1 cDNA and compare it with its
      human homolog, the -14 gene, and another human cDNA sequence named hProx1. Our
      results show a strong conservation between the -14 gene and the mouse Prox1 gene
      with the exception of the first exon of the mProx1 gene. This exon is absent in
      the -14 cDNA but is present and conserved in the human Prox1 cDNA, indicating
      that the human -14/hProx1 gene is alternatively spliced or transcribed. The
      mProx1 gene encodes a predicted protein of 491 amino acids (aa) whose function is
      not known. In the 5'UTR of this gene, a 35-bp repeat (VNTR) is positioned, which
      is highly polymorphic among laboratory inbred mice (Mus domesticus). Our results
      strongly suggest that the mProx1 VNTR arose during the divergence of M. spretus
      and M. domesticus. Besides its use in evolutionary studies and positional
      cloning, the mProx1 VNTR might be invaluable for monitoring the expression of a
      transgenic mProx1 gene. The cloning of the mProx1 gene will be helpful to analyze
      its possible role on alpha-globin as well on MPG expression in the mouse.

PMID- 8995758
TI  - Genetic mapping of 18S ribosomal RNA-related loci to mouse chromosomes 5, 6, 9,
      12, 17, 18, 19, and X.
AB  - The organization of ribosomal RNA genes (rDNA) in the genome of the mouse varies
      significantly from one strain to another, but has been shown to follow the
      pattern of clusters of tandem repeats located at chromosome ends, often
      associated with cytological nucleolus organizer regions. The number of copies of
      the repeat unit at each locus also varies. A probe for the 18S ribosomal RNA
      sequence on Southern blots reveals both high copy number bands and fainter bands
      indicative of low repeat number. We have mapped a number of newly identified low
      copy-number rDNA loci in C57BL/6J, in addition to placing some of the NOR
      associated rDNA repeats on the Jackson interspecific backcross (BSS) map. We
      suggest that additional low-copy-number loci may remain to be mapped, and that
      the evolution of rDNA loci in the genome may include the proliferation of single
      copies by retroinsertion or other mechanisms.

PMID- 8995757
TI  - Rbt (Rabo torcido), a new mouse skeletal mutation involved in anteroposterior
      patterning of the axial skeleton, maps close to the Ts (tail-short) locus and
      distal to the Sox9 locus on chromosome 11.
AB  - Rbt (Rabo torcido) is a new semidominant mouse mutant with a variety of skeletal
      abnormalities. Heterozygous Rbt mutants display homeotic anteroposterior
      patterning problems along the axial skeleton that resemble Polycomb group and
      trithorax gene mutations. In addition, the Rbt mutant displays strong
      similarities to the phenotype observed in Ts (Tail-short), indicating also a
      homeotically transformed phenotype in these mice. We have mapped the Rbt locus to
      an interval of approximately 6 cM on mouse Chromosome (Chr) 11 between
      microsatellite markers D11Mit128 and D11Mit103. The Ts locus was mapped within a
      shorter interval of approximately 3 cM between D11Mit128 and D11Mit203. This
      indicates that Rbt and Ts may be allelic mutations. Sox9, the human homolog of
      which is responsible for the skeletal malformation syndrome campomelic dysplasia,
      was mapped proximal to D11Mit128. It is, therefore, unlikely that Ts and Rbt are
      mouse models for this human skeletal disorder.

PMID- 8995759
TI  - A rat mutation producing demyelination (dmy) maps to chromosome 17.
AB  - A recessive mutation exhibiting severe myelin breakdown, mainly at the level of
      the lumbar segments of the spinal cord and without any associated inflammation,
      was discovered in a partially inbred rat colony. Analysis of the segregation
      patterns of a set of polymorphic microsatellite markers in two inter-strain
      crosses allowed the mapping of this autosomal recessive mutation to rat
      Chromosome (Chr) 17, very close to the prolactin (Prl) locus, in a region
      homologous to human Chr 6p21.2-22.3 and mouse Chr 13. The pathology of the
      demyelination process and the chromosomal localization indicate that this
      mutation has no known equivalent in either mouse or human.

PMID- 8995760
TI  - A missense mutation in the gene for melanocyte-stimulating hormone receptor
      (MC1R) is associated with the chestnut coat color in horses.
AB  - The melanocyte-stimulating hormone receptor gene (MC1R) is the major candidate
      gene for the chestnut coat color in horses since it is assumed to be controlled
      by an allele at the extension locus. MC1R sequences were PCR amplified from
      chestnut (e/e) and non-chestnut (E/-) horses. A single-strand conformation
      polymorphism was found that showed a complete association to the chestnut coat
      color among 144 horses representing 12 breeds. Sequence analysis revealed a
      single missense mutation (83Ser-->Phe) in the MC1R allele associated with the
      chestnut color. The substitution occurs in the second transmembrane region, which
      apparently plays a key role in the molecule since substitutions associated with
      coat color variants in mice and cattle as well as red hair and fair skin in
      humans are found in this part of the molecule. We propose that the now reported
      mutation is likely to be the causative mutation for the chestnut coat color. The
      polymorphism can be detected with a simple PCR-RFLP test, since the mutation
      creates a TaqI restriction site in the chestnut allele.

PMID- 8995761
TI  - Structural organization and mammary-specific expression of the butyrophilin gene.
AB  - Butyrophilin is a glycoprotein of the immunoglobulin superfamily that is secreted
      in association with the milk-fat-globule membrane from mammary epithelial cells.
      As a first step towards determining the possible function(s) of this protein in
      lactation, the mouse butyrophilin gene (Btn) has been cloned from a 129-ES cell
      genomic library. Over 14 kb of DNA was sequenced, including the entire
      transcriptional unit of the gene, and 4.6 kb and 1.1 kb of the 5' and 3' flanking
      region, respectively. In addition, the overall structure of the bovine gene (BTN)
      was determined by amplification of genomic DNA by the polymerase chain reaction.
      Both Btn and BTN comprise seven exons and six introns. The signal sequence and
      two immunoglobulin-like folds of the exoplasmic domain and the membrane anchor
      are encoded by separate exons, and the cytoplasmic domain is encoded by two short
      exons and a large terminal exon that also includes 3' untranslated sequence. The
      butyrophilin gene appears to have evolved from a subset of genes in the
      immunoglobulin superfamily and genes encoding the B30.2 domain, which is
      conserved in a family of zinc-finger proteins. Murine butyrophilin mRNA was
      detected specifically in the mammary gland by RNase protection analysis.
      Expression increased during the last half of pregnancy and was maximal during
      lactation. The 5' flanking region of Btn was analyzed for putative regulatory
      elements and is different from the promoters of other mammary-specific genes. Btn
      should be useful for determining the mechanisms underlying mammary-specific gene
      expression and potentially for the production of heterologous proteins in the
      milk of transgenic animals.

PMID- 8995763
TI  - Genetic mapping of thymine DNA glycosylase (Tdg) gene and of one pseudogene in
      the mouse.

PMID- 8995762
TI  - Cloning, sequencing, and chromosomal localization of two tandemly arranged human
      pseudogenes for the proliferating cell nuclear antigen (PCNA).
AB  - We have characterized a human genomic clone carrying two pseudogenes for the
      proliferating cell nuclear antigen (PCNA), which were tandemly arranged on human
      Chromosome (Chr) 4. One is a processed pseudogene that showed a 73% nucleotide
      homology to the human PCNA cDNA and possessed none of the introns existing in the
      functional PCNA gene. This pseudogene presumably arose by reverse transcription
      of a PCNA mRNA followed by integration of the cDNA into the genome. The other is
      a 5' and 3' truncated pseudogene that showed a nucleotide homology to a 3' region
      of the exon 4 and to a 5' region of the exon 5 of the PCNA gene and did not have
      the intronic sequence between the exons 4 and 5. Both pseudogenes had the same
      nucleotide deletion as compared with the human functional PCNA gene. A
      phylogenetic analysis of PCNA gene family, including the functional PCNA gene and
      another PCNA pseudogene located on a different chromosome, revealed that the
      truncated pseudogene exhibits the closest evolutionary relationship with the
      processed pseudogene, suggesting that the truncated pseudogene was generated by
      duplication of the processed pseudogene after translocation to Chr 4.
      Furthermore, fluorescence in situ hybridization revealed that these pseudogenes
      are located on the long arm of Chr 4, 4q24.

PMID- 8995764
TI  - Genomic organization of TUPLE1/HIRA: a gene implicated in DiGeorge syndrome.

PMID- 8995765
TI  - The human H-twist gene is located at 7p21 and encodes a B-HLH protein that is 96%
      similar to its murine M-twist counterpart.

PMID- 8995766
TI  - The gene for microtubule-associated protein 4 (Mtap4) maps to the distal region
      of mouse chromosome 9.

PMID- 8995767
TI  - Genes encoding the acetaminophen and selenium binding proteins map to mouse
      chromosome 3.

PMID- 8995769
TI  - The mouse Prkacn2 gene encoding protein kinase A inhibitor 2 is located on
      proximal chromosome 10.

PMID- 8995768
TI  - Mapping of the novel G protein-coupled receptor Gpr18 to distal mouse chromosome
      14.

PMID- 8995771
TI  - Mapping of the rat Ptn gene to chromosome 4.

PMID- 8995770
TI  - Chinese hamster transducin gene (GNAT2): genomic organization and peptide
      conservation.

PMID- 8995772
TI  - Localization of a Moloney murine leukemia virus integration site gene, Mlvi2, on
      rat chromosome 2.

PMID- 8995773
TI  - Carbon-based packing materials for liquid chromatography: applications.

PMID- 8995774
TI  - Sample preparation for gas chromatography with solid-phase extraction and solid
      phase microextraction.

PMID- 8995775
TI  - Capillary electrophoresis of proteins.

PMID- 8995776
TI  - Chiral micelle polymers for chiral separations in capillary electrophoresis.

PMID- 8995777
TI  - Analysis of derivatized peptides using high-performance liquid chromatography and
      capillary electrophoresis.

PMID- 8995778
TI  - African American children in the modern child welfare system: a legacy of the
      Flemming Rule.
AB  - Children of color throughout America-and especially those who are African
      American-are disproportionately represented in the child welfare system. This
      article links this current child welfare condition to the most significant but
      little known ruling in the historical development of the modern child welfare
      system-the Flemming Rule. The Flemming Rule, although intended to be
      constructive, was negatively implemented in a way that has had long-term serious
      consequences for African American children and their families. Implications for
      future policies are discussed.

PMID- 8995779
TI  - Child protection risk assessment and African American children: cultural
      ramifications for families and communities.
AB  - Child welfare practitioners are increasingly employing formal and structured risk
      assessment processes to predict child vulnerability or to improve case decision
      making. In general, research has neither proved conclusively which set of risk
      factors are most critical for evaluating risk within a family and community, nor
      has it resolved the controversy regarding the importance of professional training
      and experience in risk assessment procedures and processes. There is, however, a
      beginning recognition of the importance of collaborative strategies that bring
      community representatives to the assessment table along with the traditional
      professionals. The author argues for urgency in the pursuit of a dialogue that
      examines varied definitions of harm and risk for children, and the implications
      of those definitions for cultural conflict, screening and intake, and resource
      allocation.

PMID- 8995780
TI  - An out-of-home care system in crisis: implications for African American children
      in the child welfare system.
AB  - An out-of-home care system that is itself in crisis lacks adequate resources to
      provide the services needed by families and children in distress. Increasingly,
      these families are composed of people of color, particularly African Americans.
      Using current child welfare statistics and a review of the literature, this
      article examines the nature of the crisis in child welfare, and how poverty and
      an array of social problems, as well as problems specific to the child welfare
      system, increase the overrepresentation of African American children and families
      in the out-of-home care system. Implications for child welfare practice and
      advocacy are also discussed.

PMID- 8995781
TI  - African American families and HIV/AIDS: caring for surviving children.
AB  - This article presents the preliminary findings of a national project undertaken
      to examine the medical/health, social service, and legal needs of African
      American children who have experienced or will experience the death of one or
      both parents as a result of HIV/AIDS. The project seeks to guide the development
      of culturally competent policies and practices across delivery systems
      responsible for managing the care of these children and their families. Services
      have expanded for the children but much remains to be accomplished to achieve
      culturally competent, integrated care systems for surviving children and their
      caregivers.

PMID- 8995782
TI  - "Of mind, body, and spirit": therapeutic foster care--an innovative approach to
      healing from an NTU perspective.
AB  - This article examines Progressive Life Center's (PLC) innovative Therapeutic
      Foster Care (TFC) program, and its incorporation of a unique clinical approach,
      NTU (pronounced in-to) psychotherapy, into its program model. PLC is an African
      American private nonprofit community-based organization that strives to improve
      the delivery of mental health services through culturally competent therapeutic
      techniques. PLC expanded its services to include TFC for seriously emotionally
      disturbed children, ages 2 to 18. All PLC services are delivered within the
      spiritual and cultural framework of NTU.

PMID- 8995783
TI  - African American female adolescent identity development: a three-dimensional
      perspective.
AB  - African American female adolescents have unique identity issues that structure
      developmental tasks. Qualitative data from a longitudinal research project are
      used to explicate a three-dimensional model of the identity developmental process
      in early-age African American female adolescents. The limitations of a gender
      analysis model of voice and connection are noted. It is suggested that the
      African American female adolescent experiences a relational crisis in both racial
      and gender identity development. Moreover, African American female adolescents
      develop skillful, unique, expressionistic, and assertive styles of relating to
      negotiating perceived hostile environments. Practice implications for child
      welfare are outlined.

PMID- 8995784
TI  - A rite of passage approach designed to preserve the families of substance-abusing
      African American women.
AB  - This article approaches the treatment of addicted African American women in ways
      drawn from traditional African culture. While the modern African American woman
      is clearly not the same as her continental African foremother, the reality of her
      life is still predicated on the basis of her culture and her material wealth or
      lack of it. The approach recommended here, a rite of passage, derives from the
      belief that the value orientations drawn from the African wisdom of the ages
      offers the best way to work with families to recover both sobriety and a powerful
      understanding and repossession of culture that will help to ensure not only
      sobriety but also ways of holding together and rebuilding the families of today
      and the future.

PMID- 8995785
TI  - An Afrocentric program for African American males in the juvenile justice system.
AB  - Though the juvenile justice system provides an array of interventions, culturally
      relevant programs are necessary to deal with the myriad social problems,
      including an escalating crime rate, facing high-risk African American adolescent
      males. This article presents an Afrocentric approach to service delivery for
      these youths and their families.

PMID- 8995786
TI  - An eye color gene for the detection of transgenic non-drosophilid insects.
AB  - A genetic marker for identifying transgenic Musca domestica by changes in eye
      color is described. The Drosophila melanogaster tryptophan oxygenase gene,
      vermilion (v), was tested for its ability to genetically complement the mutant
      tryptophan oxygenase gene in houseflies homozygous for green (ge). The v cDNA,
      placed under the control of the hsp82 promoter of D. pseudoobscura was
      transiently expressed in M. domestica embryos homozygous for the tryptophan
      oxygenase gene, ge, resulting in the rescue of adult eye color. The use of a gene
      from D. melanogaster to complement an eye color mutant in Musca provides the
      opportunity to develop a gene vector system for M. domestica and a select group
      of other non-drosophilid insects in which homologous mutations exist.

PMID- 8995787
TI  - Inhibitors of CYP6D1 in house fly microsomes.
AB  - CYP6D1 is a cytochrome P450 responsible for the metabolism of insecticides and
      other xenobiotics in the house fly (Musca domestica). Using a CYP6D1-specific
      monooxygenase activity and a non-CYP6D1-specific monooxygenase activity, 21
      compounds were evaluated as inhibitors of CYP6D1 in house fly microsomes. CYP6D1
      was strongly inhibited by xanthotoxin, chlorpyrifos, beta-naphthoflavone,
      piperonyl butoxide and 5-methoxypsoralen. The highest selectivity for inhibition
      of CYP6D1 was seen for 5-methoxypsoralen, xanthotoxin, beta-naphthoflavone,
      chlorpyrifos oxon, isosafrole and psoralen. The results clearly indicate that
      identification of isoform-selective inhibitors of P450s within an insect, and
      across species, is possible. In addition, psoralen and 5-methoxypsoralen
      stimulated ethoxycoumarin O-deethylation suggesting that these compounds were
      substrates for monooxygenases in house fly microsomes. Isosafrole was shown to be
      a potent synergist of pyrethroid insecticides in adult house flies.

PMID- 8995788
TI  - Trypsin and aminopeptidase gene expression is affected by age and food
      composition in Anopheles gambiae.
AB  - The effects of age and food composition on the expression of trypsin and
      aminopeptidase genes in the Anopheles gambiae gut were investigated. No trypsin
      mRNA was detected in the gut of newly eclosed females, but this mRNA accumulated
      to relatively high levels within the first day of life. In contrast, low, but
      significant trypsin enzyme activity was observed in newly eclosed females.
      Subcellular fractionation experiments suggested that abdominal distention induces
      the secretion of the enzyme into the lumen. Blood, but not a protein-free meal,
      induced the accumulation of new trypsin mRNA and enzyme. Unlike trypsin,
      substantial aminopeptidase activity was detected in newly eclosed and in older,
      sugar fed mosquitoes. Moreover, the subcellular localization of aminopeptidase
      did not change appreciably with food ingestion, and the early increase of enzyme
      activity was independent of food composition.

PMID- 8995789
TI  - Evidence for a DNA homologous pairing activity in nuclear extracts from mosquito
      cells.
AB  - Using a sensitive homologous pairing/DNA strand transfer assay, we detected
      formation of joint molecules in the presence of nuclear extract from cultured
      mosquito C7-10 cells in a reaction containing single stranded circular m13 DNA
      and a linear, double stranded DNA 5'-end-labeled on the strand complementary to a
      portion of the single-stranded substrate. Joint molecules were detected by the
      reduced electrophoretic mobility of labeled probe on agarose gels, which
      indicated that the 5'-end labeled strand of the linear duplex had formed a hybrid
      with the single-stranded substrate. Characterization of the activity detected
      initially in crude nuclear extracts provided a basis for a 5-fold enrichment of
      activity after a two-step KCl elution from heparin-Sepharose. Further
      purification by preparative electrophoresis yielded a band at approximately 35
      kDa, which, when transferred to Immobilon P membrane, specifically bound the
      labeled, complementary strand probe. Optimal activity of the electroeluted enzyme
      required both magnesium and ATP and was sensitive to the ratio of single-stranded
      and double-stranded DNA substrate and to the amount of protein. This homologous
      pairing activity from mosquito cells is the first such activity to be described
      from an insect other than Drosophila melanogaster.

PMID- 8995790
TI  - Identification of a Bombyx collagenous protein with multiple short domains of Gly
      Xaa-Yaa repeats: cDNA characterization and regulation of expression.
AB  - Using a differential screening strategy, a 2 kb cDNA was isolated from a
      differentiating Bombyx mori imaginal wing discs library. The available reading
      frame of 1710 bp specifies a conceptual protein with two distinct regions: a 395
      amino acid region corresponding to 105 repetitions of the Gly-Xaa-Yaa triple
      helical forming unit arranged in 9 domains of 12-54 residues interspaced by short
      interruptions of 3-17 residues and a C-terminal domain of 175 amino acids
      devoided of triplets. These characteristics suggest that the encoded protein is a
      new member of the collagen superfamily, the first one characterized in Bombyx.
      Northern blots reveal a unique 7.4 kb mRNA in imaginal wing discs, epidermis and
      brain. In wing discs, the 7.4 kb transcripts accumulate during the last larval
      moult and the spinning stage. In vitro studies reveal that this accumulation is
      dose dependent and detectable within 1 h in response to 20-hydroxyecdysone which
      acts without de novo protein synthesis. A model of regulation of transcript
      accumulation with regards to the hormonal level is proposed.

PMID- 8995791
TI  - Inducibility of the Drosophila melanogaster cytochrome P450 gene, CYP6A2, by
      phenobarbital in insecticide susceptible or resistant strains.
AB  - The importance of cytochrome P450s in the biology of cells or organisms is
      clearly established. While numerous studies concern vertebrates, little is known
      about invertebrates cytochrome P450s. In this paper, we have focused on CYP6A2
      gene expression in Drosophila melanogaster. We show the expression of this
      cytochrome P450 gene in the Canton(s) strain (wild type) to be under the control
      of phenobarbital. In adults treated with phenobarbital, this gene is transcribed
      in the midgut, the pericuticular fat bodies and the Malpighian tubules. The
      induction factor is 15. In the RDDTR strain of Drosophila melanogaster, which is
      resistant to the insecticide DDT, this gene is constitutively overexpressed in
      the same tissues (overexpression factor is 6 relative to untreated Canton(s)
      flies). Phenobarbital is not as effective on RDDTR (induction factor is 2.5
      relative to untreated RDDTR flies) as on wild type strains.

PMID- 8995792
TI  - Detection and quantification of a very high density lipoprotein in different
      tissues of Triatoma infestans during the last nymphal and adult stages.
AB  - The presence of a very high density lipoprotein (VHDL), an hexameric protein, was
      explored in different tissues of Triatoma infestans throughout the last nymphal
      and adult stages, and in egg extracts by Western blot assays. The VHDL was always
      detected in both, hemolymph and fat body, during the above mentioned stages and
      it was also observed in the buffer soluble fraction of testis and egg
      homogenates. An enzyme-linked immunosorbent assay (ELISA) was used to measure the
      VHDL titer in these tissues. Hemolymph VHDL reaches a maximum value before the
      last molt, then it abruptly declines in males and females just after emergence,
      but during adult life it increases again. Fat body VHDL decreases slowly and
      continuously during the nymph growth reaching a minimum value prior to molting,
      and in the first week of adult life the values were even two-fold lower; then, it
      shows a different cycle of accumulation and depletion in males and females. In
      adult testis the VHDL undergoes a cycle similar to the one observed in male fat
      body. This protein increases progressively during embryonic development and, at
      the time of larval hatching it reaches its maximum value. The hexameric protein
      presents homologies in its N-terminal sequence with storage hexamerins of
      Diptera, Lepidoptera and Hymenoptera.

PMID- 8995794
TI  - Characterization of muscarinic binding sites in the central nervous system of
      larval Manduca sexta.
AB  - Putative muscarinic receptors (mAChRs) were characterized in the CNS of larval
      Manduca sexta through the binding of 3H-quinuclidyl benzilate ([3H]-QNB).
      Specific binding isotherms revealed a high affinity binding site in both crude
      homogenates (Ka = 3.22 +/- 0.62 nM-1 (Kd 0.311 nM), Bmax = 65.4 +/- 9.8 fmoles/mg
      protein) and in purified membrane preparations (Ka = 7.61 +/- 1.78 nM-1 (Kd 0.130
      nM), Bmax = 22.8 +/- 2.15 fmoles/mg protein). In purified membrane preparations
      the binding was complex, consisting of at least two sites (Hill coefficient =
      0.514 +/- 0.041). Because of the high proportion of non-specific binding at QNB
      concentrations greater than 10 nM, the binding parameters for the additional low
      affinity site could not be determined accurately but the Kd was estimated to be
      greater than 8 nM. Complex binding was also exhibited in the kinetics of [3H]-QNB
      association and dissociation in purified membranes. Analysis resolved two high
      affinity sites (dissociation rate constants = 80.4 and 1.2 min, Kds = 0.272 and
      0.909 nM, consisting of 65.9 +/- 3.7 and 26 +/- 4.9% of the sites respectively).
      Presumably, the high affinity site identified in saturation studies consists of
      these two components. The primary high affinity site was isolated using a
      dissociative method and its pharmacology determined in competition studies. [3H]
      QNB binding at this site was displaced by pirenzepine and methoctramine (Kis =
      248 and 707 nM) closely matching the pharmacology of the cloned Drosophila mAChR.
      Competition data for 4-DAMP were better fitted by a two site model (Kis = 37 and
      547 nM). These results demonstrate unexpected complexity in muscarinic ligand
      binding and are consistent with mAChR heterogeneity in the CNS of Manduca.

PMID- 8995793
TI  - NAD(P)H-dependent production of oxygen reactive species by the salivary glands of
      the mosquito Anopheles albimanus.
AB  - Salivary gland homogenates of the adult female mosquito Anopheles albimanus, but
      not those of Aedes aegypti, induced light production in the presence of NADPH and
      luminol, indicating a NADPH oxidase activity producing reactive oxygen species
      (superoxide anion) by the anopheline salivary homogenate. Superoxide production
      by the anopheline salivary homogenate was also confirmed by the NADPH-dependent,
      superoxide dismutase inhibitable, reduction of cytochrome c. The NADPH oxidase
      reaction measured by light production in the presence of luminol was inhibited by
      superoxide dismutase and catalase. Both NADH and NADPH were substrates for the
      production of oxygen reactive species by the salivary homogenate. Activity, as
      measured by luminol-dependent light emission, was enhanced one order of magnitude
      in the presence of 1.6 mg/ml of either phosphatidylserine or bovine serum
      albumin. Molecular sieving and hydroxyapatite chromatography of the salivary
      homogenate showed coelution of the NADPH oxidase activity with the previously
      reported salivary peroxidase activity. It is suggested that the salivary
      peroxidase of Anopheles albimanus has the ability of producing superoxide in the
      presence of NADPH, and this may provide the peroxidase with substrates necessary
      for peroxidation of vasoconstrictor amines such as serotonin, released by
      aggregating platelets at the site of mosquito probing and feeding.

PMID- 8995797
TI  - Systematic study of the genus Vogesella gen. nov. and its type species, Vogesella
      indigofera comb. nov.
AB  - A blue-pigmented colony that had a metallic copper-colored sheen was isolated in
      1973 from a standard spread plate count preparation of oxidation pond sediment.
      Over the next 11 years, an additional 12 strains of blue-pigmented bacteria were
      isolated from freshwater samples and compared to several reference strains of
      bacteria. Morphological and biochemical tests revealed that these 13 isolates
      were very similar to [Pseudomonas] indigofera ATCC 19706T (T = type strain) and
      ATCC 14036. A numerical analysis (in which simple matching similarity
      coefficients were clustered by the unweighted pair group mathematical averaging
      method) of morphological and biochemical characteristics revealed 90.0%
      relatedness between the 13 isolates and [P.] indigofera ATCC 19706T and ATCC
      14036 and 73.6% relatedness between the 13 isolates and a cluster containing
      Burkholderia cepacia ATCC 25416T, Janthinobacterium lividum ATCC 12473T, and the
      Pseudomonas species tested. A phylogenetic analysis, in which both 5S rRNA and
      16S rRNA were used, also revealed that the 13 isolates were closely related to
      each other and to strains ATCC 19706T and ATCC 14036. In addition, both 5S rRNA
      and 16S rRNA analyses demonstrated that the isolates and strains ATCC 19706T and
      ATCC 14036 were members of the beta subdivision of the Proteobacteria and were
      closely related to Chromobacterium violaceum ATCC 12742T but sufficiently
      distinct to warrant placement in a new genus. Accordingly, we propose that the 13
      isolates and strains ATCC 19706T and ATCC 14306 be placed in the genus Vogesella
      gen. nov., which is named in honor of Otto Voges, who first isolated and
      described this blue-pigmented eubacterium in 1893. We also propose that [P.]
      indigofera be renamed Vogesella indigofera comb. nov. and designated the type
      species of the genus; strain ATCC 19706 is the type strain of this species.

PMID- 8995796
TI  - Phylogenetic analysis of Borrelia burgdorferi sensu stricto by arbitrarily primed
      PCR and pulsed-field gel electrophoresis.
AB  - Borrelia burgdorferi sensu lato is present all over the world. However, most
      species belonging to this complex have a limited distribution; the only exception
      is B. burgdorferi sensu stricto, which is encountered both in Europe and in the
      United States. The aim of this study was to clarify the way that B. burgdorferi
      sensu stricto migrated. To do this, we compared the genetic polymorphism of 33 B.
      burgdorferi sensu stricto strains isolated in Europe and 28 strains isolated in
      the United States by using both pulsed-field gel electrophoresis and arbitrarily
      primed PCR. Phylogenetic analysis of each of the two sets of data was performed
      by a genetic distance method and a parsimony method. The results were consistent
      and revealed that the American strains were more heterogeneous than the European
      strains. The hypothesis that B. burgdorferi sensu stricto was introduced to
      Europe from America rather than vice versa has to be considered.

PMID- 8995795
TI  - A phylogenetic analysis of Borrelia burgdorferi sensu lato based on sequence
      information from the hbb gene, coding for a histone-like protein.
AB  - We describe a phylogenetic investigation of Borrelia burgdorferi sensu lato, the
      causative agent of Lyme disease, based on a DNA sequence analysis of the hbb
      gene, which encodes protein HBb, a member of the family of histone-like proteins.
      Because of their intimate contact with the DNA molecule, these proteins are
      believed to be fairly conserved through evolution. In this study we proved that
      the hbb gene is suitable for phylogenetic inference in the genus Borrelia. The
      hbb gene, which is 327 bp long and encodes 108 amino acids, was sequenced for 39
      strains, including 37 strains of B. burgdorferi sensu lato, 1 strain of Borrelia
      turicatae, and 1 strain of Borrelia parkeri. Genetic variability was determined
      at the sequence level by computational analysis. Briefly, 81 substitutions were
      scored at the DNA level. Only 25 of these substitutions were responsible for
      amino acid substitutions at the translational level. The signature region for
      bacterial histone-like proteins was found in hbb. Although variable at the
      nucleotide level, it was highly conserved at the deduced amino acid level. A
      phylogenetic tree for the genus Borrelia that was generated from multiple
      sequence alignments was consistent with previously published data derived from
      DNA-DNA hybridization and multilocus enzyme electrophoresis analyses. The
      subdivision of B. burgdorferi sensu lato into five species (B. burgdorferi sensu
      stricto, Borrelia garinii, Borrelia afzelii, Borrelia japonica, and "Borrelia
      andersonii") and at least four genomic groups (groups PotiB2, VS116, CA2, and
      DN127) was confirmed.

PMID- 8995798
TI  - Aerococcus urinae: intraspecies genetic and phenotypic relatedness.
AB  - A number of Aerococcus-like organisms were recently recognized as human
      pathogens. Five Aerococcus-like strains were proposed as members of the new
      species Aerococcus urinae (with type strain E2 [= NCTC 12142]) on the basis of
      the results of a 16S rRNA sequence analysis. The intraspecies phenotypic and
      genetic relatedness of 22 selected A. urinae strains was investigated, and a
      hitherto unrecognized esculin hydrolysis-positive biotype was identified. A total
      of 14 of the 15 more common esculin-negative strains exhibited very high DNA
      relatedness as determined by the hydroxyapatite method (the levels of relatedness
      were greater than 90% in 55 and 70 degrees C reactions, with 1.5% or less
      divergence in related sequences). The DNA relatedness among the six esculin
      positive strains was more heterogeneous, and two DNA hybridization subgroups were
      formed. Our results are compatible with the hypothesis that both biotypes are
      members of the single species A. urinae, which contains two or more genetic
      subspecies. The putative subspecies have not been formally proposed since they
      cannot be definitively differentiated. The inclusion of A. urinae in the genus
      Aerococcus is supported by the results of 16S rRNA sequencing. The rRNA sequence
      data also is compatible with placing both biotypes in a single species.

PMID- 8995799
TI  - Phylogenetic analysis of mycoplasmas based on Hsp70 sequences: cloning of the
      dnaK (hsp70) gene region of Mycoplasma capricolum.
AB  - A 5.0-kb region containing the hsp70 (dnaK) gene was cloned from Mycoplasma
      capricolum and sequenced. In addition to the hsp70 gene, this sequence region
      also contained the complete sequences for the grpE and orfA genes and partial
      sequences for the clpB and dnaJ genes. The order of the above gene sequences in
      the cloned fragment was found to be clpB-orfA-grpE-hsp70-dnaJ, which is similar
      to the order seen in various other gram-positive groups of bacteria. The Hsp70
      homologs from two mycoplasma species, Mycoplasma capricolum and Mycoplasma
      genitalium, contain a number of sequence signatures, including the absence of a
      large insert in the N-terminal quadrant, that are characteristics of the homologs
      from gram-positive bacteria and archaebacteria. A detailed phylogenetic analysis
      based on Hsp70 sequences was also performed. In neighbor-joining and parsimony
      trees based on Hsp70 sequences, both mycoplasma species branched with the low-G +
      C-content gram-positive group of bacteria (e.g., Lactobacillus and Erysipelothrix
      species) in 87% and 96% of the bootstrap replicates, respectively, indicating
      their close evolutionary relationship to this group. The phylogenetic trees based
      on Hsp70 sequences show a polyphyletic branching of archaebacteria with the gram
      postive species, which is statistically strongly favored.

PMID- 8995800
TI  - Phylogenetic analysis of the genus Actinomyces based on 16S rRNA gene sequences:
      description of Arcanobacterium phocae sp. nov., Arcanobacterium bernardiae comb.
      nov., and Arcanobacterium pyogenes comb. nov.
AB  - A systematic phylogenetic analysis of the genus Actinomyces was performed. The
      16S rRNA gene sequences of 13 Actinomyces species, an unnamed Actinomyces strain
      (ATCC 49338), and an Actinomyces-like isolate from sea mammals were determined.
      Comparative sequence analysis with closely related taxa revealed phylogenetic
      diversity and internal structure within the genus Actinomyces. In addition, some
      members of other genera (viz., the genera Arcanobacterium, Mobiluncus, and
      Rothia) were shown to be phylogenetically intermixed with the Actinomyces
      species. It was evident from both distance and tree topology considerations that
      the genus Actinomyces is in urgent need of taxonomic revision and requires
      subdivision into several genera. Based on the results of the present study it is
      proposed that Actinomyces bernardiae and Actinomyces pyogenes be assigned to the
      genus Arcanobacterium as Arcanobacterium bernardiae comb. nov. and
      Arcanobacterium pyogenes comb. nov., respectively. In addition, a new species,
      Arcanobacterium phocae, is proposed for Actinomyces-like bacteria isolated from
      seals.

PMID- 8995801
TI  - Comparative sequence analyses of the genes coding for 16S rRNA of Lactobacillus
      casei-related taxa.
AB  - The primary structures of the 16S rRNA genes of the type strains of Lactobacillus
      casei and related taxa were determined by PCR DNA-sequencing methods. The
      sequences of Lactobacillus casei, Lactobacillus zeae, Lactobacillus paracasei,
      and Lactobacillus rhamnosus were different. The Knuc values ranged from 0.0040 to
      0.0126. On the basis of the Knuc values and the levels of DNA-DNA relatedness
      among the strains of these species, the L. casei-related taxa should be
      classified in the following three species: L. zeae, which includes the type
      strains of L. zeae and L. casei; a species that includes the strains of L.
      paracasei and L. casei ATCC 334; and L. rhamnosus.

PMID- 8995802
TI  - Vibrio scophthalmi sp. nov., a new species from turbot (Scophthalmus maximus).
AB  - Six strains isolated from the intestines of juvenile turbot in a fish hatchery in
      the north of Spain were found to be phenotypically members of the genus Vibrio.
      However, the phenotypic traits of these organisms did not place them in any of
      the currently known Vibrio species. These isolates formed an homogeneous group in
      which the DNA-DNA similarity values (the differences between the thermal
      denaturation midpoints of the homologous and heterologous duplexes) with
      reference strain A089T (T = type strain) ranged from 0 to 1.7 degrees C. The
      results of a 16S rRNA sequence analysis of A089T placed this strain in the genus
      Vibrio in the gamma subclass of the Proteobacteria. The closest relative is
      Vibrio aestuarianus, with a sequence similarity of 97.8%. This group of strains
      can be easily differentiated from the other Vibrio species by their clear
      phenotype. We propose the name Vibrio scophthalmi sp. nov. for these strains; the
      type strain is strain A089 (= CECT 4638).

PMID- 8995803
TI  - Occurrence of lipoteichoic acid in oral streptococci.
AB  - The heterogeneous bacterial group known as oral streptococci was screened for the
      presence of cellular polyglycerolphosphate-containing lipoteichoic acid. This
      compound was detected in phenol extracts of lyophilized cells by an immunoassay
      in which polyglycerolphosphate-specific monoclonal antibody was used.
      Polyglycerolphosphate-containing lipoteichoic acid occurred in all 86 strains of
      oral streptococci examined except the Streptococcus mitis and Streptococcus
      oralis strains. This confirms the findings of Rosan (B. Rosan, Science 201:918
      920, 1978) and Hamada et al. (S. Hamada, J. Mizuno, S. Kotani, and M. Torii, FEMS
      Microbiol. Lett. 8:93-96, 1980), is consistent with the results of the taxonomic
      study of oral streptococci performed by Kilian et al. (M. Kilian, L. Mikkelsen,
      and J. Henrichsen, Int. J. Syst. Bacteriol. 39:471-484, 1989), who emended the
      descriptions of Streptococcus sanguis, S. oralis, and S. mitis, and reflects the
      phylogenetic relationship among S. mitis, S. oralis, and Streptococcus
      pneumoniae.

PMID- 8995804
TI  - Treponema medium sp. nov., isolated from human subgingival dental plaque.
AB  - A new Treponema species, for which we propose the name Treponema medium, was
      isolated from subgingival plaque from an adult with periodontal disease. The
      morphological characteristics, differential biochemical characteristics, and
      protein profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      gels of this organism are described. The guanine-plus-cytosine content of the DNA
      of T. medium is 51 mol%. The levels of DNA-DNA relatedness of the new species to
      other Treponema species, including Treponema denticola, Treponema vincentii,
      Treponema socranskii, Treponema pallidum, and Treponema phagedenis, are less than
      30%. A phylogenetic analysis based on 16S rRNA sequences distinguished the new
      Treponema strain from strains belonging to previously described Treponema
      species. The type strain of T. medium is strain G7201.

PMID- 8995805
TI  - Haloarcula argentinensis sp. nov. and Haloarcula mukohataei sp. nov., two new
      extremely halophilic archaea collected in Argentina.
AB  - Strains arg-1T (T = type strain) and arg-2T, two new strains of extremely
      halophilic archaea, were isolated from the soils of the Argentine salt flats. The
      taxonomic features of arg-1T were similar to, but distinct from, those of the
      type strain of Haloarcula vallismortis and other Haloarcula species. On the 16S
      rRNA phylogenetic tree, strain arg-1T formed a cluster together with Haloarcula
      species. Strain arg-2T differed in its glycolipid composition but still was more
      closely related to the genus Haloarcula than to other established genera. We
      propose that strain arg-1T be classified as a member of a new species, Haloarcula
      argentinensis, and that strain arg-2T be classified as a member of Haloarcula
      mukohataei sp. nov., although arg-2T may belong to a new genus or a subgenus of
      the genus Haloarcula. The type strain of H. argentinensis is strain arg-1 (= JCM
      9737), and the type strain of H. mukohataei is strain arg-2 (= JCM 9738).

PMID- 8995806
TI  - Spiroplasma diabroticae sp. nov., from the southern corn rootworm beetle,
      Diabrotica undecimpunctata (Coleoptera:Chrysomelidae).
AB  - Spiroplasma strain DU-1T (T = type strain), which was isolated from hemolymph of
      the corn rootworm Diabrotica undecimpunctata (Coleoptera:Chrysomelidae), was
      serologically distinct from other spiroplasma species, groups, and subgroups.
      Cells of strain DU-1T were shown by light microscopy to be helical motile
      filaments. Electron microscopy revealed cells bounded by a single cytoplasmic
      membrane, with no evidence of a cell wall. The organism was not sensitive to 500
      U of penicillin per ml. Strain DU-1T grew well in SM-1, M1D, and SP-4 liquid
      media, in broth supplemented with 1% bovine serum fraction or conventional horse
      serum, and under both aerobic and anaerobic conditions. This organism did not
      appear to have a sterol requirement for growth, as has been reported for several
      other Spiroplasma species or strains. Optimal growth occurred at 32 degrees C,
      with a doubling time of 0.9 h; strain DU-1T multiplied at 10 to 41 degrees C but
      failed to grow at 5 or 43 degrees C. It produced acid from glucose but hydrolyzed
      neither arginine nor urea. The results of reciprocal serologic tests in which
      antigens or antisera to established Spiroplasma species, groups, subgroups, and
      putative groups were used indicated that strain DU-1T was serologically distinct.
      This organism has a DNA guanine-plus-cytosine content of 25 +/- 1 mol% and a
      genome size of 1,350 kbp. Strain DU-1T is a member of a cluster of fast-growing
      insect-associated spiroplasmas, as determined by sequence analysis of 16S rRNA.
      On the basis of the results of this study and previously published data, strain
      DU-1 (= ATCC 43210) is designated the type strain of a new species, Spiroplasma
      diabroticae.

PMID- 8995807
TI  - Streptococcus difficile is a nonhemolytic group B, type Ib Streptococcus.
AB  - Whole-cell protein electrophoretic analysis of the type strain of Streptococcus
      difficile (LMG 15799) revealed that this organism was indistinguishable from
      Streptococcus agalactiae strains. Although LMG 15799T (T = type strain) was
      originally described as serologically untypeable, we found that this strain was a
      group B streptococcus belonging to the capsular polysaccharide antigen type Ib
      group. The biochemical reactivity of S. difficile, which differed from the
      biochemical reactivity of typical S. agalactiae strains mainly by being less
      versatile, is similar to the biochemical reactivity of other group B, type Ib
      streptococci isolated from poikilothermic animals, such as fish and frogs.

PMID- 8995808
TI  - Mycobacterium hassiacum sp. nov., a new rapidly growing thermophilic
      mycobacterium.
AB  - A new rapidly growing, scotochromogenic mycobacterium was isolated from urine.
      This strain is thermophilic (it grows at 65 degrees C), tolerates 5% NaCl, and
      was unable to utilize any of the sugars tested or citrate or to take up iron. The
      isolate splits benzamide, urea, nicotinamide, and pyrazinamide and is sensitive
      to streptomycin, ethambutol, cycloserine, ciprofloxacin, and chlarithromycin but
      resistant to isoniazid, rifampin, and prothionamide. These characteristics
      clearly place this organism in a new mycobacterial species, which was confirmed
      by the unique 16S rRNA nucleotide sequence. The high level of similarity between
      this rapid grower and Mycobacterium xenopi is surprising. For this new rapidly
      growing scotochromogenic and thermophilic mycobacterium we propose the name
      Mycobacterium hassiacum sp. nov.

PMID- 8995809
TI  - Corynebacterium coyleae sp. nov., isolated from human clinical specimens.
AB  - Over a 5-year period, six isolates of a previously unknown nonlipophilic
      coryneform bacterium were isolated from human clinical specimens. The most
      characteristic phenotypic reactions of these isolates included slow fermentative
      acid production from glucose but no acid production from maltose and sucrose and
      a strongly positive CAMP reaction. Chemotaxonomic investigations revealed that
      meso-diaminopimelic acid and mycolic acids were present, that palmitic, oleic,
      and stearic acids were the predominant cellular fatty acids, and that the G + C
      content was 62 to 64 mol%, characteristics which are consistent with assignment
      to the genus Corynebacterium. Phenotypically, the unknown coryneform bacterium
      could be readily differentiated from all other Corynebacterium species. A 16S
      rRNA gene sequence analysis and quantitative DNA-DNA hybridization experiments
      demonstrated unambiguously that the unknown coryneform bacterium is a member of
      the genus Corynebacterium and is genotypically distinct from all other members of
      this genus. Based on phenotypic and genotypic findings, a new species,
      Corynebacterium coyleae sp.nov., is proposed. The type strain of C coylease is
      strain DSM 44184 (= CCUG 35014).

PMID- 8995811
TI  - Investigations of the taxonomy and systematics of Fusobacterium nucleatum using
      allozyme electrophoresis.
AB  - Fusobacterium nucleatum forms part of the resident microbiota in both oral and
      extraoral sites in humans and animals. It is also involved in infections in such
      sites. Despite the genetic heterogeneity within the species, it has been divided
      into five subspecies, the validities of which have been questioned. In the
      present study, 44 F. nucleatum isolates were examined at 21 enzyme loci by using
      the allozyme electrophoretic technique to establish an accurate genetic framework
      for taxonomic purposes. Three distinct genetic clusters were identified; one
      cluster consisted exclusively of extraoral isolates, another cluster consisted
      predominantly of human oral isolates, and the third cluster consisted of a single
      human oral isolate. Our results highlight the urgent need for extensive
      biochemical, immunological, and epidemiological studies to accurately define the
      systematics of the genus fusobacterium based on the framework derived in this
      study by using 21 independent genetic characteristics.

PMID- 8995810
TI  - A new genus of the order Actinomycetales, Spirilliplanes gen. nov., with
      description of Spirilliplanes yamanashiensis sp. nov.
AB  - Actinomycete strain YU127-1T (T = type strain), which produces zoospores, was
      isolated from a soil sample. The aerial mycelium of this organism at maturity
      forms short chains of spores. The hyphae form coils, and sporangia are not
      observed. Strain YU127-1T contains glutamic acid, glucosamine, glycine, alanine,
      and meso-diaminopimelic acid in its cell wall (wall chemotype II), 3-O
      methylmannose, mannose, xylose, and glucose as whole-cell sugars, meanaquinone
      10(H4), and glycolyl cell wall polysaccharides and has a guanine-plus-cytosine
      content of 69.0 mol%. Mycolic acids are absent. Phosphatidylinositol and
      phosphatidylethanolamine are diagnostic phospholipids. The chemotaxonomic data,
      except for the lack of arabinose in the whole-cell sugars, indicate that this
      strain belongs to the family Micromonosporaceae. The morphological and
      physiological characteristics and chemotaxonomic and phylogenetic data for this
      strain differ from those of the previously described actinomycetes. We therefore
      propose a new genus, spirilliplanes, for this organism; the type species of the
      genus is Spirilliplanes yamanashiensis sp. nov., and the type strain of S.
      yamanashiensis is strain YU127-1 (= IFO 15828).

PMID- 8995812
TI  - Moraxella boevrei sp. nov., a new Moraxella species found in goats.
AB  - Six Moraxella-like strains that formed a phenotypically homogeneous group were
      isolated from the nasal flora of healthy goats. Total genomic DNA-DNA
      hybridization, rRNA gene restriction pattern, DNA base composition, and genetic
      transformation studies were performed to determine the relationships of these
      bacteria to species belonging to the genus Moraxella and other fastidious gram
      negative species. The new group of isolates was very homogeneous, as shown by
      rRNA gene restriction fragment length patterns (ribotyping), and these organisms
      displayed high relative binding ratios (RBRs) to each other in DNA-DNA
      hybridization experiments (RBRs, > or = 58%) but distinctly lower levels of DNA
      homology with all other species investigated. However, the RBRs obtained with
      species of the genus Moraxella were higher than the RBRs obtained with all other
      gram-negative strains examined. Although the new strains had most of the
      Moraxella bovis phenotypic characteristics except nitrate reduction, quantitative
      and qualitative genetic transformation data led to the conclusion that they
      belong to a distinct new cluster in the genus Moraxella. The results of this
      study, combined with the general morphological and phenotypic profiles of the new
      strains, are consistent with the creation of a new Moraxella species, for which
      the name Moraxella boevrei is proposed. Strain 88365 (= ATCG 700022 = CCUG 35435
      = NCTC 12925 = CIP 104716) is the type strain of M. boevrei.

PMID- 8995813
TI  - Thermonema rossianum sp. nov., a new thermophilic and slightly halophilic species
      from saline hot springs in Naples, Italy.
AB  - Six slightly halophilic, thermophilic bacterial strains were isolated from saline
      hot springs along the Bay of Naples, Italy. These strains produce bright yellow
      colonies and have a filamentous morphology and an optimum growth temperature of
      about 60 degrees C. Lipid composition and 16S ribosomal DNA sequence analyses
      showed that these strains belong to the genus Thermonema, a member of the
      cytophaga-flavobacter-bacteroides phylum. Growth was observed in medium
      containing 1 to 3% NaCl. The DNA G + C content was 50.9 mol%. DNA-DNA
      hybridization studies showed that these strains represent a new species of the
      genus Thermonema. We propose that strain NR-27T (T = type strain) and the other
      strains represent a new species, Thermonema rossianum. Strain NR-27 (= DSM 10300)
      is the type strain of this species.

PMID- 8995814
TI  - A proposal to reclassify Nocardia pinensis Blackall et al. as Skermania
      piniformis gen. nov., comb. nov.
AB  - The type strain of Nocardia pinensis was the subject of chemotaxonomic and 16S
      ribosomal DNA sequencing studies. The resultant nucleotide sequence was aligned
      with the sequences of representatives of the genera Corynebacterium, Dietzia,
      Gordona, Mycobacterium, Nocardia, Rhodococcus, and Tsukamurella, and phylogenetic
      trees were generated by using the Fitch-Margoliash, maximum-parsimony, maximum
      likelihood, and neighbor-joining methods. It was evident from the phylogenetic
      analyses that N. pinensis represents a distinct phyletic line that is most
      closely associated with the Gordona clade. This genealogical evidence, together
      with chemotaxonomic and phenotypic data derived from this and previous studies,
      indicates that N. pinensis merits generic status within the family Nocardiaceae.
      Therefore, we propose that N. pinensis Blackall et al. 1989 be reclassified as
      Skermania piniformis gen. nov., comb. nov. The type strain of Skermania
      piniformis cleaved an array of conjugated substrates based on the fluorophores 7
      amino-4-methylcoumarin and 4-methylumbelliferone.

PMID- 8995815
TI  - Genome organization of Pseudomonas stutzeri and resulting taxonomic and
      evolutionary considerations.
AB  - In order to determine the genome variability within Pseudomonas stutzeri, 20
      strains representing the seven described genomovars and strain JM300 were
      analyzed by using various resolution levels of rare cutting enzymes. XbaI and
      SpeI fingerprints revealed a high degree of heterogeneity of restriction patterns
      that did not correlate with the division into genomovars. However, a fragment
      pattern comparison led to the establishment of several groups of clonal variants
      within genomovars. One circular chromosome ranging in size from 3.75 to 4.64 Mb
      constitutes the genome of P. stutzeri strains. The I-CeuI, PacI, and SwaI low
      resolution map of P. stutzeri type strain CCUG 11256 shows the locations of 12
      genes, including rrn operons and the origin of replication. I-CeuI digests of the
      20 strains studied plus the positions of six genes allowed a comparison of the
      rrn backbone organization within genomovars; the four rrn operons seemed to be at
      similar locations with respect to the origin of replication, as did the rest of
      the genes. However, a comparison of I-CeuI cleavage maps of the genomovar
      reference strains revealed a diverse genome organization in the genomovars
      relative to rrn operons and gene locations. In most genomovars, rrn operons are
      not arranged around the origin of replication but are equally distributed on the
      chromosome. Strain JM300 does not belong to any described genomovar, as
      determined from the organization of its genome. Large chromosomal rearrangements
      seem to be responsible for the differences in superordinate genome structure and
      must have played an important role in P. stutzeri diversification and niche
      colonization. An ancestral chromosome is suggested, and some plausible pathways
      for the generation of the various genome structures are proposed.

PMID- 8995816
TI  - Desulfonatronovibrio hydrogenovorans gen. nov., sp. nov., an alkaliphilic,
      sulfate-reducing bacterium.
AB  - A new alkaliphilic, sulfate-reducing bacterium, strain Z-7935T (T = type strain),
      was isolated from a soda-depositing lake, Lake Magadi in Kenya. This organism is
      a motile vibrio which utilizes only hydrogen and formate as electron donors and
      sulfate, sulfite, and thiosulfate, but not sulfur, as electron acceptors.
      Thiosulfate is dismutated. Strain Z-7935T is an obligately sodium-dependent
      alkaliphile which grows in sodium carbonate medium and does not grow at pH 7; the
      maximum pH for growth is more than pH 10, and the optimum pH is 9.5 to 9.7. The
      optimum NaCl concentration for growth is 3% (wt/vol). The optimum temperature for
      growth is 37 degrees C. The G + C content of the DNA is 48.6 mol%. 16S ribosomal
      DNA sequence analysis revealed that strain Z-7935T represents a new lineage with
      genus status in the delta subclass of the Proteobacteria. The name
      Desulfonatronovibrio hydrogenovorans gen. nov., sp. nov. is proposed for this
      organism; the type strain of D. hydrogenovorans is strain Z-7935 (= DSM 9292).

PMID- 8995817
TI  - Anaerobaculum thermoterrenum gen. nov., sp. nov., a novel, thermophilic bacterium
      which ferments citrate.
AB  - A thermophilic anaerobic bacterium designated strain RWcit2T (T = type strain)
      was isolated from the production water of a petroleum reservoir. The cells of
      this organism are straight to slightly curved rods that are gram negative and
      nonmotile. Spore formation has not been demonstrated. Growth occurs at
      temperatures ranging from 28 to 60 degrees C, with optimum growth occurring at 55
      degrees C, and at pH values ranging from 5.5 to 8.6, with optimum growth
      occurring between pH 7 and 7.6. Growth occurs in media containing 0 to 20 g of
      NaCl per liter, and optimum growth occurs in the presence of 10 g of NaCl per
      liter. Strain RWcit2T grows on a range of organic acids, including citrate,
      pyruvate, malate, fumarate, and tartrate; on protein extracts; and on a limited
      number of carbohydrates. Sulfur, thiosulfate, and cystine are reduced to hydrogen
      sulfide. Sulfate, sulfite, and nitrate are not reduced. The DNA base composition
      is 44 mol% G + C. The 16S ribosomal DNA sequence revealed that strain RWcit2T is
      a member of the domain Bacteria and forms a branch that is approximately
      equidistant from Dictyoglomus thermophilium and Thermoanaerobacter spp. (level of
      similarity, 82%). Strain RWcit2T cannot be placed in any previously described
      taxon based on its phylogenetic and physiological traits and is named
      Anaerobaculum thermoterrenum gen. nov., sp. nov.

PMID- 8995818
TI  - Schwartzia succinivorans gen. nov., sp. nov., another ruminal bacterium utilizing
      succinate as the sole energy source.
AB  - Four strains of gram-negative, anaerobic, non-spore-forming bacteria that were
      curved rods which were motile by means of flagella originating from the concave
      side of the cells and which fermented succinate quantitatively to propionate were
      isolated from high dilutions of rumen ingesta obtained from cows on pasture. The
      bacteria were asaccharolytic and not proteolytic and did not ferment amino acids
      or peptides. Succinate was the only substrate fermented. Rumen fluid together
      with yeast extract was required for good growth on succinate. Growth on succinate
      was enhanced in the presence of fumarate. The strains did not grow at 22 degrees
      C, and growth at 45 degrees C was in all cases less than growth at 39 degrees C.
      The cellular fatty acid compositions of all four strains were determined. The DNA
      base composition was about 46 mol% G + C. The complete 16S ribosomal DNA sequence
      of the type strain (strain S1-1) was determined, and the phylogenetic
      relationships were analyzed. The most closely related genera were the genera
      Selenomonas, Zymophilus, and Pectinatus, whereas the recently described succinate
      fermenting organism Succiniclasticum ruminis was distantly related. The name
      proposed for these strains is Schwartzia succinivorans gen. nov., sp. nov.; the
      type strain is strain S1-1 (= DSM 10502). These organisms are common inhabitants
      of the rumina of cows on pasture.

PMID- 8995819
TI  - Stenotrophomonas africana sp. nov., an opportunistic human pathogen in Africa.
AB  - A gram-negative bacterium was isolated from a cerebrospinal fluid sample from an
      HIV-seropositive Rwandan refugee with primary meningoencephalitis. This Marseille
      Goma sample B isolate, strain MGBT (T = type strain), was found to exhibit
      evolutionary homology with Stenotrophomonas maltophilia, as determined by a 16S
      rRNA gene sequence analysis, and this finding was reflected by similar phenotypic
      traits. MGBT could, however, be distinguished from the S. maltophilia type strain
      by using a number of biochemical and physiological tests, and a genotypic
      analysis of the two strains in which DNA homology was used revealed only 35%
      homology between them. Furthermore, the antibiotic susceptibility of MGBT was
      restricted to netilmicin, ciprofloxacin, trimethoprim-sulfamethoxazole, and
      colimycin. On the basis of these results we propose that MGBT is a representative
      of a new species in the genus Stenotrophomonas, Stenotrophomonas africana.

PMID- 8995820
TI  - Clostridium pascui sp. nov., a new glutamate-fermenting sporeformer from a
      pasture in Pakistan.
AB  - Four strains of an obligately anaerobic spore-forming bacterium were isolated
      from soil samples from a donkey pasture in Pakistan. Comparative 16S rRNA
      sequence analysis demonstrated that the strains are members of phylogenetic
      cluster I of the genus Clostridium (Collins et al. 1994). The strains are
      mesophilic, nonsaccharolytic, and nonproteolytic, utilize glutamate and
      histidine, and produce indole. Acetate, butyrate, ethanol, hydrogen, and carbon
      dioxide are the products of fermentation. Although the strains phenotypically
      resemble the classical glutamate-fermenting clostridia, such as Clostridium
      cochlearium, Clostridium tetanomorphum, Clostridium tetani, and especially
      Clostridium malenominatum, they differ from these organisms in sugar utilization,
      cellular fatty acid composition, and cellular protein pattern and by a 16S rRNA
      sequence divergence value of approximately 4 to 8%. Phylogenetically, the strains
      are more closely related to Clostridium estertheticum (sequence divergence,
      approximately 5%) and Clostridium subterminale (sequence divergence,
      approximately 5%) but are phenotypically readily distinguished from these
      species. On the basis of phenotypic and genotypic criteria, we conclude that the
      four strains are members of a new species of the genus Clostridium, for which the
      name Clostridium pascui is proposed. The type strain is strain Cm19 (= DSM
      10365).

PMID- 8995821
TI  - Identification of two pathogenic avian mycoplasmas as strains of Mycoplasma
      pullorum.
AB  - Two mycoplasma strains were isolated from dead turkey embryos. Growth properties,
      biochemical and serological characteristics, and protein profiles indicated that
      these strains were closely related to Mycoplasma pullorum CKKT (T = type strain).
      This was confirmed by 16S rRNA sequence analysis, and the phylogenetic position
      of M. pullorum was established. Pathogenicity studies showed that the two
      strains, as well as M. pullorum CKKT, induced a statistically significant level
      of mortality after inoculation into chicken embryos.

PMID- 8995822
TI  - Taxonomic study of aromatic-degrading bacteria from deep-terrestrial-subsurface
      sediments and description of Sphingomonas aromaticivorans sp. nov., Sphingomonas
      subterranea sp. nov., and Sphingomonas stygia sp. nov.
AB  - Phylogenetic analyses of 16S rRNA gene sequences by distance matrix and parsimony
      methods indicated that six strains of bacteria isolated from deep saturated
      Atlantic coastal plain sediments were closely related to the genus Sphingomonas.
      Five of the strains clustered with, but were distinct from, Sphingomonas
      capsulata, whereas the sixth strain was most closely related to Blastobacter
      natatorius. The five strains that clustered with S. capsulata, all of which could
      degrade aromatic compounds, were gram-negative, non-spore-forming, non-motile,
      rod-shaped organisms that produced small, yellow colonies on complex media. Their
      G + C contents ranged from 60.0 to 65.4 mol%, and the predominant isoprenoid
      quinone was ubiquinone Q-10. All of the strains were aerobic and catalase
      positive. Indole, urease, and arginine dihydrolase were not produced. Gelatin was
      not liquified, and glucose was not fermented. Sphingolipids were present in all
      strains; 2OH14:0 was the major hydroxy fatty acid, and 18:1 was a major
      constituent of cellular lipids. Acid was produced oxidatively from pentoses,
      hexoses, and disaccharides, but not from polyalcohols and indole. All of these
      characteristics indicate that the five aromatic-degrading strains should be
      placed in the genus Sphingomonas as currently defined. Phylogenetic analysis of
      16S rRNA gene sequences, DNA-DNA reassociation values, BOX-PCR genomic
      fingerprinting, differences in cellular lipid composition, and differences in
      physiological traits all indicated that the five strains represent three
      previously undescribed Sphingomonas species. Therefore, we propose the following
      new species: Sphingomonas aromaticivorans (type strain, SMCC F199), Sphingomonas
      subterranea (type strain, SMCC B0478), and Sphingomonas stygia (type strain, SMCC
      B0712).

PMID- 8995823
TI  - Discrimination of Streptomyces albidoflavus strains based on the size and number
      of 16S-23S ribosomal DNA intergenic spacers.
AB  - In an attempt to develop a rapid and accurate method for discrimination of
      streptomycetes at the strain level, 21 strains identified by fatty acid analysis
      as Streptomyces albidoflavus and the type strains of nine subjective synonyms of
      S. albidoflavus were selected for a full or partial 16S ribosomal DNA (rDNA)
      sequence analysis and an investigation of the 16S-23S rDNA intergenic spacer
      region. 16S rDNA sequence analysis showed that 27 of the strains exhibited 100%
      sequence similarity; these strains included the type strain of S. albidoflavus
      and the type strains of the subjective synonyms Streptomyces canescens,
      Streptomyces coelicolor, Streptomyces felleus, Streptomyces limosus, Streptomyces
      odorifer, and Streptomyces sampsonii. The type strains of the other subjective
      synonyms of S. albidoflavus (i.e., Streptomyces gougerotii, Streptomyces
      intermedius, and Streptomyces rutgersensis) were found to have levels of 16S rDNA
      sequence difference of 1.0 to 1.1% when they were compared to the type strain of
      S. albidoflavus. In order to discriminate between the strains which had identical
      16S rDNA sequences, the 16S-23S rDNA intergenic spacer regions were amplified and
      cloned, and the sequences of the spacer regions were determined for four S.
      albidoflavus strains, including the type strain. The 16S-23S rDNA intergenic
      spacer region was found to vary in length and sequence composition among the
      strains and within each strain. The sizes and numbers of 16S-23S rDNA intergenic
      spacer regions for the 27 strains with identical 16S rDNA sequences were
      determined by high-resolution electrophoresis of FAM-labeled PCR products and a
      subsequent size analysis with GeneScan 672 software. This was shown to be a
      useful method for discrimination of S. albidoflavus strains. Strains with the
      same 16S-23S rDNA intergenic spacer band pattern, as determined by high
      resolution electrophoresis of FAM-labeled PCR products, could be further
      discriminated on the basis of the sequence composition of the spacer region.

PMID- 8995825
TI  - Reassessment of the phylogenetic position of Caulobacter subvibrioides.
AB  - Determination of the 16S rRNA gene sequence of Caulobacter subvibrioides ATCC
      15264T (T = type strain) confirmed that this species is a member of the alpha
      subclass of the Proteobacteria and showed that it is phylogenetically most
      closely related to the Caulobacter group comprising the species Caulobacter
      bacteroides, Caulobacter crescentus, and Brevundimonas (Pseudomonas) diminuta,
      for which 16S rRNA sequences of the type strains are currently available. The
      closest known relative of strain ATCC 15264T among these species is B. diminuta
      (level of direct pairwise sequence similarity, 95%). On the basis of its
      previously determined 16S rRNA sequence (accession number M83797), C.
      subvibrioides is most closely related to Sphingomonas adhaesiva in the alpha-4
      subgroup (level of similarity, 97.7%). Analysis of the hydroxy fatty acids of C.
      subvibrioides ATCC 15264T showed that the 2-hydroxymyristic acid which is
      characteristic of the genus Sphingomonas was absent.

PMID- 8995824
TI  - A phylogenetic analysis of aerobic polychlorinated biphenyl-degrading bacteria.
AB  - Several bacterial isolates were characterized based on their abilities to degrade
      specific polychlorinated biphenyls (PCBs) and their 16S rRNA gene sequences. The
      members of one group of bacteria consisting of Alcaligenes species, including the
      PCB-degrading bacterium Alcaligenes eutrophus H850, had strong abilities to
      degrade a broad range of PCBs but not the di-para-chlorine-substituted congeners.
      The members of another group, which included the PCB-degrading bacterium
      originally classified as Corynebacterium sp. strain MB1, had strong abilities to
      degrade di-para-chlorine-substituted PCBs. These bacteria were most likely
      different members of Rhodococcus species.

PMID- 8995826
TI  - Transfer of the bacteriochlorophyll b-containing phototrophic bacteria
      Rhodopseudomonas viridis and Rhodopseudomonas sulfoviridis to the genus
      Blastochloris gen. nov.
AB  - The phylogenetic positions of the bacteriochlorophyll (BChl) b-producing budding
      phototrophic bacteria Rhodopseudomonas viridis and Rhodopseudomonas sulfoviridis
      were studied on the basis of 16S rRNA gene sequence information. These bacteria
      formed a tight cluster with the genus Rhodoplanes as a sister group within the
      alpha-2 subgroup of the Proteobacteria. Genomic DNA-DNA hybridization assays
      showed that R. viridis and R. sulfoviridis were closely related but were
      different species. Creation of the genus Blastochloris gen. nov. is proposed to
      accommodate these BChl b-producing species of phototrophic bacteria.

PMID- 8995827
TI  - Comparison of the 16S/23S ribosomal intergenic regions of "Candidatus
      Liberobacter asiaticum" and "Candidatus Liberobacter africanum," the two species
      associated with citrus huanglongbing (greening) disease.
AB  - 16S/23S intergenic spacer regions from the rRNA operons of two strains of
      "Candidatus Liberobacter asiaticum" and one strain of "Candidatus Liberobacter
      africanum" were cloned and sequenced. The intergenic spacers of the two
      "Candidatus L. asiaticum" strains studied are identical and contain the genes for
      isoleucine tRNA (tRNA(Ile)) and alanine tRNA (tRNA(Ala)) separated by 11
      nucleotides. The intergenic spacer of the "Candidatus L. africanum" strain
      contains only one tRNA gene (tRNA(Ala)). The level of homology between the
      intergenic spacers of the two liberobacter species is 79.46%. Ribosomal operons
      with 16S/23S spacer regions other than those studied might be present in the two
      "Candidatus Liberobacter" species.

PMID- 8995828
TI  - JEAB and JABA on the World Wide Web: a report to readers.
AB  - The Journal of the Experimental Analysis of Behavior (JEAB) and the Journal of
      Applied Behavior Analysis (JABA) have both established home pages on the World
      Wide Web. Their addresses are: http://www.envmed.rochester.edu/wwwrap/beh
      avior/jeab/jeabhome.htm http://www.envmed.rochester.edu/wwwrap/beh
      avior/jaba/jabahome.htm An important feature of these pages is a powerful program
      that permits rapid full-text searches of a database consisting of the nearly
      5,000 abstracts that have accompanied articles published in JEAB since 1958 and
      in JABA since 1968. An electronic version of a single article from each issue of
      each journal is now made available soon after the paper edition of the journal
      appears.

PMID- 8995829
TI  - Functional analysis and treatment of cigarette pica.
AB  - A series of analyses was conducted to assess and treat the pica of cigarette
      butts by a young man with mental retardation and autism. First, we demonstrated
      that pica was maintained in a condition with no social consequences when the
      available cigarettes contained nicotine but not when the cigarettes contained
      herbs without nicotine. Second, a choice assessment (Fisher et al., 1992)
      confirmed that tobacco was preferred over the other components of the cigarette
      (e.g., paper, filter, etc.). Third, an analogue functional analysis (Iwata,
      Dorsey, Slifer, Bauman & Richman, 1982/1994) demonstrated that cigarette pica was
      maintained independent of social consequences. Fourth, a treatment designed to
      interrupt the hypothesized response-reinforcer relationship reduced consumption
      of cigarettes to zero. Finally, because cigarette pica occurred primarily when
      the individual was alone or under minimal supervision, a procedure based on
      stimulus control was developed to improve the effectiveness of the intervention
      in these situations.

PMID- 8995830
TI  - Variant and invariant high-probability requests: increasing appropriate behaviors
      in children with emotional-behavioral disorders.
AB  - This study examined the effects of variant versus invariant high-probability
      (high-p) request sequences on the performance of requests to initiate a social
      bid by young children with emotional-behavioral disorders. In the initial phases
      of the investigation, a multiple baseline design showed that the delivery of
      invariant sequences (i.e., high-p requests delivered in the same sequence)
      produced initial increases in compliance to requests to initiate a social bid to
      a peer. However, increases were not maintained across the invariant condition.
      The delivery of variant high-p sequences produced increases in compliance to
      requests to initiate social bids that were maintained across the variant
      condition. In a follow-up condition, the number of requests within the pool of
      the variant and invariant high-p requests were controlled. Results of the follow
      up condition replicated those found in the initial condition. Implications for
      applied use and future research are discussed.

PMID- 8995831
TI  - Sequential application of major habit-reversal components to treat motor tics in
      children.
AB  - In this study, we sequentially administered up to four components of the habit
      reversal treatment to 4 children with motor tics within a multiple baseline
      design. The habit-reversal components included (a) awareness training; (b)
      awareness training and self-monitoring; (c) awareness training, self-monitoring,
      and social support; and (d) awareness training, social support, and the use of a
      competing response. Results demonstrated that the combined use of awareness
      training, social support, and competing response training was effective in
      eliminating motor tics in 2 of 4 children, that awareness training alone was
      effective for 1 child, and that a combination of awareness training and self
      monitoring was effective for the 4th child. The treatment and ensuing improvement
      were found to be socially valid. We discuss possible explanations for these
      results and recommend directions for future research.

PMID- 8995833
TI  - The effects of instructional match and content overlap on generalized reading
      performance.
AB  - This study examined the effects of instructional match and content overlap on
      students' ability to generalize from passage reading instruction. Four students
      with mild disabilities served as participants. Using a multielement design,
      students were instructed with passages at two levels of text difficulty
      (instructionally matched vs. instructionally mismatched), and generalization was
      assessed with passages at two levels of similarity to those instructed (low vs.
      high content overlap). Results indicated that students' oral reading accuracy and
      fluency showed the greatest degree of generalization when instructional materials
      were matched to the students' skill level and assessment materials were similar
      to those used during instruction. Moreover, these results were maintained at 1
      month follow-up. The implications of these findings for classroom reading
      instruction and the assessment of students' reading skills are discussed.

PMID- 8995832
TI  - An experimental comparison of three different schedules of reinforcement of drug
      abstinence using cigarette smoking as an exemplar.
AB  - The efficacy of three different schedules of reinforcement for promoting and
      sustaining drug abstinence was compared in this study. Cigarette smoking was
      studied as an exemplar of stimulant drug self-administration. Sixty cigarette
      smokers were assigned to one of three groups (progressive rate of reinforcement,
      fixed rate of reinforcement, and yoked control). Participants in all three groups
      were asked to refrain from smoking for 1 week. Participants in the progressive
      and fixed groups achieved greater mean levels of abstinence than those in the
      control group. Participants in the progressive group were significantly less
      likely to resume smoking when they became abstinent than participants in the
      other groups.

PMID- 8995834
TI  - Evaluation of a multiple-stimulus presentation format for assessing reinforcer
      preferences.
AB  - We compared three methods for presenting stimuli during reinforcer-preference
      assessments: a paired-stimulus format (PS), a multiple-stimulus format in which
      selections were made with replacement (MSW), and a multiple-stimulus format in
      which selections were made without replacement (MSWO). Results obtained for 7
      participants showed moderate to high rank-order correlations between the MSWO and
      PS procedures and a similar number of identified reinforcers. In addition, the
      time to administer the MSWO procedure was comparable to that required for the MSW
      method and less than half that required to administer the PS procedure.
      Subsequent tests of reinforcement effects revealed that some stimuli selected in
      the PS and MSWO procedures, but not selected in the MSW procedure, functioned as
      reinforcers for arbitrary responses. These preliminary results suggest that the
      multiple-stimulus procedure without replacement may share the respective
      advantages of the other methods.

PMID- 8995835
TI  - In pursuit of general behavioral relations.
AB  - Efforts to develop behavioral technologies from advances in basic research assume
      that results from studies with nonhuman subjects can, in some instances, be
      applied to human behavior. The behavioral principles likely to be most useful for
      application are those that represent robust general behavioral relations. Basic
      and applied research on behavioral momentum suggests that there is a general
      behavioral relation between the persistence of behavior and the rate of
      reinforcement obtained in a given situation. Understanding the factors that
      affect behavioral persistence may have important implications for applied
      behavior analysts that justify studies aimed at establishing the generality and
      limits of the functional relation between reinforcement rate and behavioral
      persistence. Strategies for establishing the generality of behavioral relations
      are reviewed, followed by a brief summary of the evidence for the generality of
      behavioral momentum.

PMID- 8995836
TI  - Effects of extinction alone and extinction plus functional communication training
      on covariation of problem behaviors.
AB  - In this investigation, extinction (EXT) was applied alone or in combination with
      functional communication training (FCT) to less severe topographies of problem
      behavior while more severe topographies continued to be reinforced. EXT alone
      decreased less severe and increased more severe topographies of problem behavior
      (i.e., response covariation), whereas EXT with FCT reduced all topographies of
      problem behavior to near-zero levels.

PMID- 8995837
TI  - Differential reinforcement of alternative behavior and demand fading in the
      treatment of escape-maintained destructive behavior.
AB  - The escape-maintained destructive behavior of a boy with autism was reduced
      during instructional sequences with differential reinforcement of compliance
      (DRA), escape extinction without physical guidance, and demand fading. The
      procedure decreased destructive behaviors to near-zero levels and greatly
      increased compliance.

PMID- 8995838
TI  - Treating total liquid refusal with backward chaining and fading.
AB  - In this study, we report on a 12-year-old boy with autism, mental retardation,
      and a history of severe gastrointestinal problems who presented with total liquid
      and food refusal. Backward chaining was used to shape drinking from a cup, and a
      fading procedure was used to increase the quantity of water he was required to
      drink.

PMID- 8995839
TI  - Using reinforcement-based methods to enhance membership recruitment in a
      volunteer organization.
AB  - The present study employed reinforcement-based methods to induce existing members
      to recruit new members to join a chamber of commerce. Three interventions took
      place during June and July of 3 successive years. The investigators trained
      chamber leaders to use reinforcement methods (e.g., contingent tokens) to
      reinforce recruitment and dues collections. All three interventions produced
      substantial increases in their targets.

PMID- 8995840
TI  - A preliminary analysis of the effects of prior classroom conditions on
      performance under analogue analysis conditions.
AB  - We systematically manipulated two prior classroom conditions to explore their
      effects on performance under analogue assessments for a 7-year-old girl with
      severe intellectual disabilities who exhibited aggressive behavior. Results
      demonstrated consistently higher levels of aggression during demand analogue
      conditions when they were preceded by one of the classroom conditions.

PMID- 8995841
TI  - Observing N-acetyl aspartate via both its N-acetyl and its strongly coupled
      aspartate groups in in vivo proton magnetic resonance spectroscopy.
AB  - The approximately 2.6 ppm aspartate multiplet of N-acetyl aspartate (NAA) is
      considered a potential source of additional information on N-acetyl aspartate in
      vivo. Because the aspartate multiplet is the AB part of a strongly coupled ABX
      system it gives rise, as is shown in the analysis presented, to a significant
      field-strength dependence in the echo-time-dependent modulations of the response
      to typical spatial-localization sequences. The echo-time dependence of this
      response is developed analytically, not only for the STEAM and the PRESS
      localization sequences, but also for a spin-echo sequence. It is then verified
      experimentally at 2.35 T. The field-strength dependence of the response is
      demonstrated by evaluating the changes in the echo-time-dependent responses to
      each of the three sequences at field strengths of 1.5, 2.35, and 4.0 T. By means
      of these results, the preferred sequence (PRESS) can be optimized for the NAA
      aspartate multiplet at each field strength, as is illustrated with the human
      brain spectra obtained in vivo at 1.5 T. These in vivo spectra compare the
      optimal, long TE timing (163 ms) with a suboptimal TE (70 ms), for the
      observation of the approximately 2.6 ppm aspartate resonances of NAA.

PMID- 8995842
TI  - A three-dimensional NMR imaging scheme utilizing doubly resonant gradient coils.
AB  - A 3DFT gradient-echo technique has been developed which, in conjunction with
      series-resonant gradient-coil circuits, can produce three-dimensional NMR images
      with an echo time of less than 100 microseconds. The method involves a read
      gradient waveform composed of two sinusoids of different frequencies. This is an
      improvement on previous imaging sequences using a single sinusoid where only half
      of k space was sampled and where the second half was calculated using conjugate
      symmetry. The inaccuracies involved in the necessary "cut and paste" of k space
      inevitably lead to artifacts in the final image. The important features of the
      new method are that with suitable phase encoding all octants of k space are
      sampled, the RF pulse is applied when the gradients are all zero, and the echo
      forms when the gradient is essentially constant. This method will allow more
      extensive application of solid imaging techniques to biological samples in vivo.

PMID- 8995843
TI  - HCN, a triple-resonance NMR technique for selective observation of histidine and
      tryptophan side chains in 13C/15N-labeled proteins.
AB  - HCN, a new 3D NMR technique for stepwise coherence transfer from 1H to 13C to 15N
      and reverse through direct spin couplings 1JCH and 1JCN, is presented as a method
      for detection and assignment of histidine and tryptophan side-chain 1H, 13C, and
      15N resonances in uniformly 13C/15N-labeled proteins. Product-operator
      calculations of cross-peak volumes vs adjustable delay tau 3 were employed for
      determination of optimal tau 3. For the phosphatidylinositol 3-kinase (PI3K SH3
      domain, MW = 9.6 kD) at pH 6, H(C)N, the 1H/15N projection, produced observable
      cross peaks within 20 min. and was completely selective for the single tryptophan
      and single histidine. The 3D HCN experiment yielded well-defined cross peaks in
      20 h for the 13C/15N-labeled origin-specific DNA binding domain from simian virus
      40 T-antigen (T-ag-OBD131-259, MW = 15.4 kD) at pH 5.5. Resonances from all six
      histidines in T-ag-OBD were observed, and 11 of the 12 1H and 13C chemical shifts
      and 10 of the 12 15N chemical shifts were determined. The 13C dimension proved
      essential in assignment of the multiply overlapping 1H and 15N resonances. From
      the spectra recorded at a single pH, three of the imidazoles were essentially
      neutral and the other three were partially protonated (22-37%). HCN yielded
      strong cross peaks after 18 h on a 2.0 mM sample of phenylmethanesulfonyl
      fluoride (PMSF)-inhibited alpha-lytic protease (MW = 19.8 kD) at pH 4.4. No
      spectra have been obtained, however, of native or boronic acid-inhibited alpha
      lytic protease after 18 h at various temperatures ranging from 5 to 55 degrees C,
      probably due to efficient relaxation of active-site imidazole 1H and/or 15N
      nuclei.

PMID- 8995844
TI  - Extracting quantitative information from two- and three-dimensional NOE spectra
      measured with short recycle delays.

PMID- 8995845
TI  - In vivo imaging of nitroxide-free-radical clearance in the rat, using
      radiofrequency longitudinally detected ESR imaging.

PMID- 8995846
TI  - NMR pulse schemes for the sequential assignment of arginine side-chain H epsilon
      protons.

PMID- 8995847
TI  - Career preferences of medical students: some unanswered questions.

PMID- 8995848
TI  - Learning for a multicultural society.

PMID- 8995849
TI  - Morbidity and prescribing patterns for the middle-aged population of Scotland.
AB  - BACKGROUND: As part of a large national survey of morbidity recording on general
      practice computers, morbidity and prescribing data were collected from three
      separate sources for more than 10,000 patients aged 45-64 years, randomly
      selected from 41 Scottish general practices. AIM: To amalgamate the three sources
      of data to provide estimates of prevalence rates for a range of common chronic
      diagnoses, and of medication rates for associated repeat prescription drugs.
      METHOD: Forty-one Scottish general practices were selected on a geographic basis
      in relation to the national population distribution. Within each practice, 250
      patients aged 45-64 years were selected at random. Data relating to 19 diagnoses
      and 40 repeat prescription drugs were extracted from the computer records of
      these patients and compared with information held on patients' paper records and
      supplied by patients in response to a postal questionnaire. After assessing the
      completeness and accuracy of computer-held information, the three sources of data
      were amalgamated according to agreed protocols. RESULTS: Lifetime prevalence
      rates are presented for each diagnosis, broken down by sex and age group.
      Differences in rates between the sexes, and with change in age, were in the
      expected direction for all diagnoses, and were matched by corresponding
      differences in entitlements to repeat prescription drugs. Comparison of these
      lifetime rates with published prevalence rates indicates a latent pool of
      morbidity within the community, which ranges from 1.0 to 10.0 times the annual
      prevalence rate for different conditions. CONCLUSION: The amalgamated data
      provide an estimate of lifetime prevalence rates for the range of conditions
      examined. They complement conventional morbidity statistics and have potential
      value in allowing the underlying management costs of specific chronic conditions
      to be evaluated.

PMID- 8995850
TI  - One-year prognosis of abdominal complaints in general practice: a prospective
      study of patients in whom no organic cause is found.
AB  - BACKGROUND: Data on the one-year prognosis of patients with non-organic, non
      acute abdominal complaints in primary care are lacking. Knowledge of prognostic
      determinants could be helpful in management and health education. AIM: To
      describe the prognosis after one year of non-organic abdominal complaints in
      general practice, and to show how this relates to socio-demographic factors,
      medical history and psychological problems. METHODS: The one-year prognosis of
      patients with non-organic abdominal complaints in a primary care setting was
      analysed in a prospective study (n = 756). Clinical and psychological factors
      were measured and their relative risks regarding unfavourable prognosis were
      calculated one year after the first consultation. RESULTS: In 68% of the patients
      examined, the abdominal complaints had either improved or disappeared by the end
      of the first year. Female sex and depressive mental state were associated with an
      unfavourable prognosis. Clinical symptoms that were significantly associated with
      persisting complaints were a combination of abdominal pain, flatulence and bowel
      irregularities; a specific description of the character of the pain by the
      patient; looser stools at the onset of the pain; long duration or recurrence,
      pyrosis; absence of visible distension; and epigastric localization of the pain
      or tenderness. CONCLUSIONS: The prognosis after one year of non-acute abdominal
      pain in general practice is better than that reported from studies of outpatient
      populations. Female sex, depressive mood and some clinical parameters are
      associated with persistent complaints one year after presentation.

PMID- 8995851
TI  - Career preferences of medical students: influence of a new four-week attachment
      in general practice.
AB  - BACKGROUND: It is not clear why medical students choose one specialty over
      another. Experiences at medical school are extremely strong determinants of
      attitudes to the medical specialties, and attitude is the most important factor
      in determining choice. AIM: This study sought to describe the factors influencing
      career choices of final year medical students, the effect of a new four-week
      attachment in general practice on career choices, and changes in career choices
      towards or away from general practice between the final year and the end of the
      preregistration house officer year. METHOD: Career preferences, and influences on
      them, were assessed by questionnaires administered to 206 medical students
      undergoing their final clinical attachment at the University of Glasgow
      immediately before and immediately after a four-week attachment in general
      practice. These were followed up by a postal questionnaire at the end of the
      preregistration house officer year. RESULTS: One hundred and thirty-one students
      returned all three questionnaires. Before the attachment, students born outside
      the UK, and those who had a previous or intercalated degree were significantly
      less likely to put general practice as a career preference; female students were
      more likely to put it as their first career choice. After the attachment, the
      number stating that it was 'likely' or 'very likely' that they would choose
      general practice as a career increased from 60 to 72--mainly through male
      students changing their preference--but after the preregistration house officer
      year it had fallen back to 56. Seventeen of the preregistration house officers
      were planning to complete posts which would qualify for GP training. Reasons for
      changing preference towards general practice were mainly to do with a dislike of
      and disillusionment with hospital medicine and with the perceived lifestyle
      advantages of general practice. Reasons for changing preference away from general
      practice were mainly to do with positive feelings about hospital medicine and a
      dislike of the management aspects of general practice. CONCLUSION: The general
      practice attachment influenced students, especially males, towards a career in
      general practice, but this effect was transient. This cohort of doctors should be
      followed up in order to discover their ultimate career choices.

PMID- 8995852
TI  - The inter-observer reproducibility of Lasegue's sign in patients with low back
      pain in general practice.
AB  - BACKGROUND: The spectrum of low back pain patients in general practice differs
      significantly from that in an orthopaedic clinic. The most frequent specific
      cause of low back pain is nerve-root irritation or compression caused by
      intervertebral protrusion, and the diagnosis is still problematic. Testing for
      Lasegue's sign could be a useful way of detecting high-risk patients, but so far
      the reproducibility of the test has been measured only in hospital-based studies.
      AIM: To assess the inter-observer reproducibility of Lasegue's sign in general
      practice. METHOD: Fifteen General practitioners from Amsterdam and the
      surrounding areas tested all consecutive low back pain patients who visited them
      during a period of two years for Lasegue's sign. The test was repeated within two
      weeks in two samples: sample I consisted of 50 consecutive low back pain
      patients; sample II consisted of all patients who had pelvic tilt, scoliosis, or
      positive Lasegue's sign. RESULTS: In sample I, the observation was repeated in 49
      patients. The Kappa coefficient was 0.33, and the proportions of positive and
      negative agreement were 33% and 96%, respectively. In sample II, the observation
      was repeated in 48 patients. The Kappa coefficient was 0.56, whereas the
      proportion of positive agreement was 67% and the proportion of negative agreement
      was 91%. CONCLUSIONS: The reproducibility of Lasegue's sign in routine general
      practice seems to be low, but may be similar to the reproducibility observed in
      hospital settings in selected patients who have a high chance of low back pain
      owing to a specific disease.

PMID- 8995853
TI  - Audit of the care of patients with epilepsy in general practice.
AB  - BACKGROUND: Previous studies have shown that there is great potential for
      improving the management of patients with epilepsy. AIM: To identify all patients
      with epilepsy, to evaluate and audit their care in relation to an annual review,
      to document seizure frequency and appropriateness of daily therapy to aid
      compliance and to propose strategies to improve these and other aspects of
      epileptic care. METHOD: An audit of the care of patients with epilepsy was
      undertaken in two King's Lynn practices with a combined population of 22,500.
      Principles for the management of epilepsy were established. From these
      principles, the following standards were agreed: 75% of patients on treatment for
      epilepsy should be seen every year, 75% of patients should have their seizure
      frequency documented, and 75% of patients should take their anti-epileptic drugs
      no more than twice daily. As a result of the first audit cycle, changes were made
      in the documentation and advice regarding treatment relating to these standards.
      RESULTS: The first audit cycle showed that 83% of patients had been seen at least
      once in the previous year, that documentation of seizure frequency existed for
      51% of patients in the past year, and that 63% of patients were taking their
      treatment no more than twice daily. The evaluation was repeated 22 months later
      and an overall improvement was demonstrated in the first two results: 95% of
      patients had been seen in the past year, 93% had had their seizure frequency
      documented; however, only 66% of patients were taking their treatment twice daily
      or less. CONCLUSION: Call and recall, and documentation of seizure frequency were
      improved by this clinical audit. However, alterations in daily therapy appeared
      difficult for a variety of reasons; for example, therapy might have been
      initiated by a hospital specialist, and patients in a stable condition might have
      been apprehensive about changes. In order to improve the care of patients with
      epilepsy, a primary care team approach is desirable within a structure of good
      specialist services.

PMID- 8995854
TI  - Is general practice audit alive and well? The view from Portsmouth.
AB  - A brief look at medical audit activity in the Portsmouth and South East Hampshire
      Health Authority area by use of a questionnaire mailed out to general
      practitioners, information from the medical audit advisory group database and the
      local health authority records. The details collected consisted of topics chosen,
      the stage of audit cycle reached, funding arrangements, practice personnel and
      the outside collaborators involved. Most general practices were found to be
      undertaking audit activity, and in some it had become integrated into the
      everyday routine.

PMID- 8995855
TI  - Overdose and termination of pregnancy: an important association?
AB  - Are taking an overdose and undergoing termination of pregnancy linked? In one
      practice this study has identified a significant association between the two
      events. If this finding is supported more widely, could one event act as a risk
      marker for the second?

PMID- 8995856
TI  - An analysis of a general practitioner's workload in a disabled housing
      development.
AB  - Workload in a newly opened disabled housing unit was studied for the years 1989,
      1993 and 1995. The impact on one general practitioner was evaluated, and
      dramatically higher consulting, referral and prescribing rates were demonstrated.
      The opening of a unit for young disabled people has important implications for
      the workload of a general practitioner and adequate resources need to be
      provided.

PMID- 8995857
TI  - The rapid access proctology clinic: an appraisal of one year's experience.
AB  - A walk-in, once-a-week clinic was established in May 1993. In the first year,
      1268 patients (954 new and 314 follow up) were seen with a reduction in waiting
      time, high patient and general practitioner satisfaction, and raised awareness of
      colorectal disease.

PMID- 8995858
TI  - The clinical problem of Bell's palsy: is treatment with steroids effective?
AB  - A general practitioner can expect to see a case of Bell's palsy once every two
      years. Though uncommon, it has aroused controversy over its definition, its
      aetiology, and the best treatment. Although the majority of cases of this
      dramatic but usually self-limiting condition are seen in primary care, most of
      the literature comes from hospital studies. The evidence from four randomized
      controlled studies shows marginal benefit for steroids with a Mantel-Haenzel
      odd's ratio of 1.63 (95% CI 1.01 to 2.64); but, because of doubt about the
      methodology in some of the studies, this result must be interpreted with caution.

PMID- 8995860
TI  - Preparing GP's for working with drug users.

PMID- 8995859
TI  - The computer research network of the Royal New Zealand College of General
      Practitioners: an approach to general practice research in New Zealand.
AB  - Computers are now in widespread use by general practitioners (GPs) in many
      countries. In New Zealand this development has advanced general practice research
      by enabling collaboration among a small population of doctors practising in
      geographically diverse locations. This paper reviews the establishment of the
      Computer Research Network of the Royal New Zealand College of General
      Practitioners (RNZCGP) and its development between 1990 and 1995. The Network
      consists of 181 general practices (approximately 450 GPs) from throughout urban
      and rural New Zealand. All participants use computers in their practices to
      record consultation notes and to generate prescriptions, investigations and
      referral forms. Computer programs developed in the RNZCGP Research Unit are run
      on commercial software in doctors' surgeries to provide anonymous, individual
      data. In addition to the routine analysis of utilization for feedback to
      participants, 13 research projects have been completed. These include
      investigations of access to general practice care, use of health services by
      individuals and families, surveillance of immunization uptake, epidemiology of
      common conditions, and the use of pharmaceuticals in general practice. The RNZCGP
      Computer Research Network is an example of a computerized general practice
      research network that has been productive without receiving significant financial
      resources or having a formal management structure.

PMID- 8995861
TI  - Video-recorded consultations.

PMID- 8995862
TI  - Treatment of dementia.

PMID- 8995863
TI  - Evidence-based learning in general practice.

PMID- 8995864
TI  - Research in primary care: the need to modify help-seeking behaviour.

PMID- 8995865
TI  - Improving the detection of psychological disorders.

PMID- 8995866
TI  - You can't mishear what is written.

PMID- 8995867
TI  - Predictive value of ultrasound in threatened miscarriage.

PMID- 8995869
TI  - How well does mortality reflect the burden of illness due to stroke?

PMID- 8995868
TI  - Inhaled drug delivery in asthma patients.

PMID- 8995870
TI  - Higher professional training within general practice: provision of courses in the
      United Kingdom.

PMID- 8995871
TI  - Defensive medical practice in context.

PMID- 8995872
TI  - The challenge of angina.

PMID- 8995873
TI  - Red pepper effect.

PMID- 8995874
TI  - Why medical illustrators should be involved in making 'new media'.

PMID- 8995875
TI  - Acromegaly, Mr Punch and caricature.
AB  - The origin of Mr Punch from the Italian Pulcinella of the Commedia dell'arte is
      well known but his feature, large hooked nose, protruding chin, kyphosis and
      sternal protrusion all in an exaggerated form also suggest the caricature of an
      acromegalic. This paper looks at the physical characteristics of acromegaly, the
      origin of Mr Punch and the development of caricature linking them together in the
      acromegalic caricature that now has a life of its own.

PMID- 8995876
TI  - The use of fluorescence markers to record prosthetic wear patterns.
AB  - An application of fluorescence photography to demonstrate wear of the
      articulating surfaces of prosthetic hip joints. The physical nature and design of
      the hip prosthesis present considerable lighting difficulties when using
      conventional lighting methods to record fine abrasions on the articular surface-
      in particular, specular reflections from the light source. A fluorescent
      technique, using a fluorescent powder, was used to document wear patterns. This
      paper describes the technique of applying a fluorescent material to the articular
      surface of both the cup and the stem of a used prosthetic joint. The excess
      material is removed, leaving miniature particles lodged within the fine abrasions
      of the worn surface. The residue is irradiated with an ultraviolet (UV) source
      and the resultant fluorescence recorded onto conventional black and white film.

PMID- 8995877
TI  - Professor Raymond Jack Last, MB, BS, FRCS, FRACS, HonFMAA (1903-1993).

PMID- 8995878
TI  - Investigating Gulf veterans' health concerns.
AB  - In order to answer the questions arising from the health concerns of Gulf
      veterans, the Defence Medical Services have collated relevant health data so that
      they may be systematically analysed. However, data coverage is limited and there
      are concerns about its quality. Intramural studies alone will not be robust
      enough to determine of veterans are experiencing an excess of ill-health so a
      programme of epidemiological studies will be commissioned in collaboration with
      the Medical Research Council.

PMID- 8995879
TI  - The Royal Naval Reserve Medical Service Medical Support Assistant revisited.

PMID- 8995880
TI  - Pathogenesis to prescription: progress in understanding and treating acid related
      disorders.

PMID- 8995881
TI  - An overview of femoral intramedullary nailing.

PMID- 8995882
TI  - Acute compartment syndrome complicating Colles' fracture.
AB  - Colles' fracture is a common injury and has a relatively high associated
      morbidity. Compartment syndrome is a rare complication, but a high index of
      suspicion must be maintained in the initial post-injury and post-reduction
      periods.

PMID- 8995883
TI  - A review of Gulf War illness.

PMID- 8995884
TI  - QARNNS recollections: nor the years condemn.

PMID- 8995885
TI  - The Navy to the rescue, or from Scapa to Sydney and home again, fifty years ago.

PMID- 8995886
TI  - We shouldn't say no to interferon.

PMID- 8995887
TI  - An outgoing teenager who attempts suicide.

PMID- 8995888
TI  - New approaches to Parkinson's.

PMID- 8995889
TI  - How to recognise myasthenia gravis.

PMID- 8995890
TI  - Stroke units: how they can help.

PMID- 8995892
TI  - Alopecia.

PMID- 8995891
TI  - Understanding the anxious patient.

PMID- 8995893
TI  - Pointers for passing the CRQ. Part 1.

PMID- 8995894
TI  - A pain in the head, or in the neck?

PMID- 8995895
TI  - Chemical face peeling: patient and peeling agent selection.

PMID- 8995896
TI  - Tretinoin and glycolic acid treatment regimens.

PMID- 8995897
TI  - Superficial micropeels: glycolic acid and alpha-hydroxy acid with kojic acid.

PMID- 8995898
TI  - Medium-depth peels.

PMID- 8995899
TI  - Deep-depth chemical peeling.
AB  - Although a wide range of peeling agents are available, few can provide the
      dramatic improvement that is seen with phenol-based peeling. The nonoccluded
      phenol-based technique described in this article has been used successfully for
      over 20 years. Due to the deeper degree of injury and more involved recovery
      period, the surgeon will be best served by not only reading about this technique,
      but also observing an experienced surgeon.

PMID- 8995900
TI  - Complications of chemical face peeling: prevention and management.

PMID- 8995901
TI  - Postoperative regimen for chemical peeling: a clinical approach.

PMID- 8995902
TI  - Congratulations to all!

PMID- 8995903
TI  - Controversies on anatomy and function of the ligaments associated with the
      temporomandibular joint: a literature survey.
AB  - Varying opinions are found in the literature regarding the role of the ligaments
      associated with the temporomandibular joint, eg, with respect to recording of
      mandibular positions and diagnosis and to treatment of patients with
      temporomandibular disorders. A literature survey was done to explore
      controversies of anatomy and function of the temporomandibular joint ligaments.
      Only 20 research-based anatomic/functional articles were registered in the Index
      Medicus system under the selected headings from 1897 to 1995. By examining the
      reference lists of the articles found, 22 more articles not included in Index
      Medicus were identified. Thus, the total number of original publications
      concerning the temporomandibular ligaments was limited. Although the conventional
      textbook descriptions of the anatomy of the ligaments are fairly consistent,
      there are several controversies and unanswered questions. Information about the
      functional role of the ligaments is especially insufficient. The results of this
      survey indicate that there is a need for additional anatomic and functional
      investigations of ligaments associated with the temporomandibular joint.

PMID- 8995904
TI  - Temporomandibular disorders: a critical review of the nature of pain and its
      assessment.
AB  - Temporomandibular disorders is a common form of chronic pain affecting the head,
      face, and jaw. The distinguishing symptoms of this disorder include pain and
      impairment of the masticatory function, and frequent display of symptoms, ranging
      from aches in the head, neck, ears, and eyes, to atypical toothaches, throat
      symptoms, and occlusal changes. It is recognized that pain is a complex,
      multifactorial experience including not only sensory dimensions, but also
      affective and cognitive factors. Recent recommendations regard temporomandibular
      disorders as a dual-axis disorder with physical and psychologic dimensions, but
      little research has incorporated measures of multidimensional pain
      characteristics in the assessment of temporomandibular disorders. This article is
      a review of the literature on the psychophysiologic factors contributing to
      temporomandibular disorders and its limitations. Recommendations for future
      research are also given.

PMID- 8995905
TI  - Physical and sexual abuse among orofacial pain patients: linkages with pain and
      psychologic distress.
AB  - This study examines the incidence of and the potential correlates of sexual and
      physical abuse among facial pain patients. An anonymous survey composed of
      standardized self-report measures of abuse, pain, and psychologic status was
      distributed to 120 adult facial pain patients following their initial
      evaluations. Forty-five questionnaires were returned by mail. In addition, 206
      charts were randomly selected from a population of 520 new patients seen at the
      Orofacial Pain Center during the same time period that data from the anonymous
      survey were collected. Results of the anonymous survey indicated that 68.9% of
      the patients reported a history of abuse. Conversely, a chart review revealed
      that only 8.5% of the patients indicated a history of abuse on the clinic
      questionnaire. History of abuse was significantly related to greater pain
      severity, depression, psychologic distress, and various personality
      characteristics. Overall, this study indicates that the assessment of the history
      of abuse may be an important factor in the evaluation and treatment of facial
      pain.

PMID- 8995906
TI  - Effect of chronic and experimental jaw muscle pain on pain-pressure thresholds
      and stimulus-response curves.
AB  - Pain-pressure thresholds (PPTs) and stimulus-response (S-R) curves in masseter
      muscles and index fingers of 11 female patients with chronic jaw-muscle pain were
      compared with that of 11 matched control subjects. Experimental hyperalgesic and
      hypoalgesic conditions in the masseter muscles of control subjects were induced
      by intramuscular injection of 5% saline and of local anesthetic, respectively.
      The PPTs were found to be significantly lower in the masseter muscles of pain
      patients than in those of control subjects. The mean slopes of the S-R curves
      were significantly steeper for the masseter muscles of pain patients (0.481 +/-
      0.213) than of control subjects (0.274 +/- 0.201, P < .0256). There were no
      statistically significant differences in PPTs or S-R curves for the index finger.
      The PPTs in masseter muscles of control subjects were not significantly affected
      by injection of 5% saline; however, the slopes of the S-R curves for the masseter
      muscles were significantly steeper for saline-injection values compared to
      baseline values (21.7% +/- 29.6%, P < .037). Injection of local anesthetic into
      masseter muscles of control subjects increased the PPTs significantly and reduced
      the slopes of the S-R curves significantly as compared to baseline values (-22.9%
      +/- 34.6%, P < .0155). The present results suggest that PPTs and S-R curves are
      valuable tools for quantitative description of chronic and experimental jaw
      muscle pain.

PMID- 8995907
TI  - Pain-pressure threshold in the head and neck region of episodic tension-type
      headache patients.
AB  - Pain-pressure thresholds of the head and neck region of 31 female patients (aged
      13 to 50 years; mean, 28.4 +/- 9.6 years) suffering from episodic tension-type
      headache and 32 female control subjects (aged 15 to 46 years; mean, 26.6 +/- 8.6
      years) were recorded with an electronic algometer by the same blinded observer.
      The multivariate analysis of variance revealed that the algometer values obtained
      from different age groups of patients and control subjects were statistically
      different, but the values for the right-side muscles were not statistically
      different from the corresponding values for the left-side muscles. The pain
      pressure thresholds of the patient group were lower than those of the control
      group for the superior sternocleidomastoid muscles, middle sternocleidomastoid
      muscles, and trapezius insertion muscles (P < .01) but were not statistically
      different for the anterior temporal, middle temporal, posterior temporal, deep
      masseter, anterior masseter, inferior masseter, medial pterygoid, posterior
      digastric, splenius capitis, and upper trapezius muscles (P > .01). The results
      may indicate that pain-pressure thresholds of the head and neck region should be
      considered in the diagnosis of episodic tension-type headache. The results may
      also propose that the increased pain sensitivity of the head and, especially, the
      neck region, may be included in the pathogenetic mechanism in episodic tension
      type headache.

PMID- 8995908
TI  - Is orthopantomography reliable for TMJ diagnosis? An experimental study on a dry
      skull.
AB  - The accuracy of orthopantomography in reproducing the temporomandibular joint
      area was analyzed on a dry skull. The results based on this study of a single
      skull revealed that the radiographic image of the temporomandibular joint did not
      correspond to the anatomic condylar and fossa components or to their actual
      relationship. To a large extent, changes in skull position affected the
      radiographic temporomandibular joint image, simulating anterior condylar
      flattening, osteophytes, narrowing of joint space, and left/right condylar
      asymmetry. Orthopantomography may have questionable reliability for
      temporomandibular joint diagnostic purposes.

PMID- 8995909
TI  - Use of Hylan G-F 20 for viscosupplementation of the temporomandibular joint for
      the management of osteoarthritis: a case report.
AB  - Viscosupplementation is a relatively new treatment concept for restoring the
      normal rheologic properties of the osteoarthritic joint. It is most often used
      for the knee. This case report describes results that were achieved using
      viscosupplementation following conservative therapy for a patient with
      osteoarthritis of the temporomandibular joint. Further study in the use of these
      treatments is recommended.

PMID- 8995910
TI  - Fibrous ankylosis of the temporomandibular joint: report of a case with atypical
      presentation.
AB  - A case of chronic unilateral mandibular dislocation with development of fibrous
      ankylosis is presented. This was an unusual presentation of intracapsular tissue
      ankylosis to the eminentia, as well as retrocondylar cicatrix combined with
      contralateral mandibular osseous compensations and remodeling with resulting
      ramus impingements upon relocation of the condyle. Various diagnostic and
      therapeutic considerations are reviewed and discussed.

PMID- 8995912
TI  - Relationship of other joint problems and anterior disc position in symptomatic
      TMD patients and in asymptomatic volunteers.
AB  - Anterior disc position has been highly correlated with temporomandibular
      disorders (TMD). It was hypothesized that internal derangement of the
      temporomandibular joint may be a part of a joint phenotype that imparts an
      increased risk for joint disorders. If this hypothesis is true, an increased
      prevalence of joint disorders in individuals diagnosed with displaced discs
      should be expected. A total of 263 symptomatic TMD patients and 82 asymptomatic
      volunteers was examined. Asymptomatic volunteers with anteriorly displaced discs
      were twice as likely as asymptomatic volunteers without disc displacements to
      report pain/dysfunction in other joints. Symptomatic patients with and without
      displaced discs reported an increase in other joint problems three to four times
      greater than in asymptomatic subjects. Compared to symptomatic TMD patients
      without disc displacement, symptomatic TMD patients with anteriorly displaced
      discs were also twice as likely to report other family members as being affected
      by TMD. Familial aggregation of TMD and an increased prevalence of other joint
      problems in these individuals may represent more than a serendipitous occurrence.

PMID- 8995911
TI  - A model for the study of experimentally induced temporomandibular arthritis in
      rats: the effect of human recombinant interleukin-1 alpha on neuropeptide-like
      immunoreactivity.
AB  - To study the interaction between human recombinant interleukin-1 alpha and the
      nervous system, substance P-, neurokinin A-, calcitonin gene-related peptide-,
      and neuropeptide Y-like immunoreactivity in the cerebrospinal fluid, plasma, and
      temporomandibular joint (TMJ) perfusates of rats during acute experimental
      monarthritis were examined. The right TMJs of the experimental rats were injected
      with 0.01 mL of human recombinant interleukin-1 alpha. The right TMJs of control
      rats were injected with 0.01 mL of saline. Cerebrospinal fluid, plasma, and
      perfusates from the right TMJs were obtained at 2, 6, and 24 hours following
      injection, and neuropeptide-like immunoreactivity was analyzed by specific
      radioimmunoassays. Values of neuropeptide-like immunoreactivity for the
      experimental rats were compared with those of the control rats. In the
      experimental group, substance P-, neurokinin A-, and calcitonin gene-related
      peptide-like immunoreactivities were increased in cerebrospinal fluid compared to
      those of the control group. In plasma, no changes in neuropeptide-like
      immunoreactivities rose significantly in the TMJ perfusates. Most pronounced
      changes in neuropeptide Y-like immunoreactivity occurred intra-articularly in the
      TMJ perfusates. The results indicate that the contribution of the nervous system
      to human recombinant interleukin-1 alpha-induced monarthritis is most pronounced
      in the affected joint.

PMID- 8995913
TI  - Signs of temporomandibular disorders in patients with horizontal mandibular
      deficiency.
AB  - This study assessed the relationship between temporomandibular disorders (TMD)
      and malocclusion in a group of 102 patients with horizontal mandibular deficiency
      who had elected mandibular advancement surgery. The prevalence of TMD as
      reflected by the overall Craniomandibular Index, Dysfunction index, and Muscle
      index scores was within the range of non TMD populations (mean Craniomandibular
      Index = 0.14; mean Dysfunction index = 0.12; mean Muscle index = 0.15). Forty-two
      percent of the patients exhibited essentially no signs of TMD, 7.8% had primarily
      muscle tenderness to palpation, 36.3% had joint sounds with or without
      temporomandibular joint tenderness, and 13.7% had combined muscle-joint signs.
      There were no convincing correlations among any of the cephalometric variables
      and Craniomandibular Index, Dysfunction index, and Muscle index scores. A
      subgroup of 30 of this patient population was evaluated both before and during
      orthodontic treatment just prior to surgery. No statistically significant changes
      were found in Craniomandibular Index, Dysfunction index, or Muscle index scores.
      Thus, a period of orthodontic treatment in these patients does not appear to
      increase the probability of TMD.

PMID- 8995914
TI  - Craniomandibular disorders in patients with Meniere's disease: a controlled
      study.
AB  - This study compares the frequency of signs and symptoms of craniomandibular
      disorders and dental conditions in patients diagnosed with Meniere's disease and
      in control subjects from a population sample. Thirty-one patients (12 men, 19
      women) diagnosed with Meniere's disease were referred from three otolaryngologic
      clinics for clinical examination and possible treatment of craniomandibular
      disorders. Thirty-one control subjects were selected from the population in the
      same area of Sweden (Ystad). Both groups were subjected to a screening of their
      symptoms with a self-administered questionnaire and to a routine stomatognathic
      examination. The function of the masticatory system was further calculated
      according to the index of Helkimo for both anamnestic dysfunction (Ai) and
      clinical dysfunction state (Di). Clinical symptoms of craniomandibular disorders
      such as pain in the face or jaw; pain on movement of the mandible; fatigue of the
      jaws; and pain located in the vertex area, the neck/shoulder area, and the
      temples all occurred significantly more often in the patient group. Findings at
      the clinical examination included a statistically higher frequency of tenderness
      to palpation of the masticatory muscles, the temporomandibular joint, and the
      upper part of the trapezius muscle in the patient group compared to that of the
      control group. The findings indicate a much higher prevalence of signs and
      symptoms of craniomandibular disorders in patients diagnosed with Meniere's
      disease than in the general population.

PMID- 8995915
TI  - Is quantitative electromyography reliable?
AB  - The reliability of quantitative electromyography (EMG) of the masticatory muscles
      was investigated in 14 subjects without any signs or symptoms of
      temporomandibular disorders. Integrated EMG activity from the anterior temporalis
      and masseter muscles was recorded bilaterally by means of bipolar surface
      electrodes during chewing and biting activities. In the first experiment, the
      influence of electrode relocation was investigated. No influence of electrode
      relocation on the recorded EMG signal could be detected. In a second experiment,
      three sessions of EMG recordings during five different chewing and biting
      activities were performed in the morning (I); 1 hour later without intermediate
      removal of the electrodes (II); and in the afternoon, using new electrodes (III).
      The method errors for different time intervals (I-II and I-III errors) for each
      muscle and each function were calculated. Depending on the time interval between
      the EMG recordings, the muscles considered, and the function performed, the
      individual errors ranged from 5% to 63%. The method error increased significantly
      (P < .05 to P < .01) with the time interval between recordings. The error for the
      masseter (mean 27.2%) was higher than for the temporalis (mean 20.0%). The
      largest function error was found during maximal biting in intercuspal position
      (mean 23.1%). Based on the findings, quantitative electromyography of the
      masticatory muscles seems to have a limited value in diagnostics and in the
      evaluation of individual treatment results.

PMID- 8995916
TI  - Relationships between risk factors and treatment outcome in a group of patients
      with temporomandibular disorders.
AB  - The aim of this study was to compare somatic complaints, anxiety, and pain
      related to temporomandibular disorders (TMD) in a group of TMD patients who had
      high scores for headache and muscle palpation compared with that of a group of
      TMD patients who had low or medium scores for headache and palpation before and 2
      years after conservative TMD treatment, consisting of counseling, muscle
      exercises, and a stabilization splint. The high-score group consisted of 23
      patients who had headaches several times a week or daily and had more than three
      muscles graded as severely tender to palpation. The low/medium-score group
      comprised 28 patients who had headaches hardly ever, once or twice a month, or
      several times a month, and with muscles graded as slightly or medium tender to
      palpation. The patients answered three questionnaires (McGill Pain Questionnaire
      [Norwegian version], a somatic complaints questionnaire, and the trait part of
      Spielberger Stait-Trait Anxiety Inventory) before and 2 years after treatment.
      The findings showed differences between the two groups concerning pain
      description, general muscle complaints, and anxiety both before and after the
      treatment, with the high-score group showing the highest values. In general, the
      treatment outcome had improved in the low/medium-score group but remained
      unchanged in the high-score group.

PMID- 8995917
TI  - Predictors of outcome for treatment of temporomandibular disorders.
AB  - Psychosocial factors have been frequently suggested as important risk factors
      that may delay recovery in patients with temporomandibular disorders. In this
      study, 94 subjects with chronic temporomandibular disorders were studied using
      IMPATH:TMJ prior to their entering an interdisciplinary treatment program to
      determine which factors were most predictive of outcome. Treatment outcome was
      determined based on significant decreases in the Craniomandibular Index and the
      Symptom Severity Index from pretreatment to posttreatment. The IMPATH:TMJ items
      were regressed on treatment outcome for a random sample of half of the subjects
      (n = 47) to isolate the psychosocial and demographic items most predictive of
      treatment response. Discriminant analysis was then employed to test the
      predictive utility of the identified items for these subjects (criterion group),
      followed by a cross-validation of the items on the remaining 47 subjects (cross
      validation group). Low self-esteem, feeling worried, low energy, and sleep
      activity were identified as useful predictors of treatment outcome for the
      criterion group. Each are correlates of depression. The discriminant analysis
      employing these four items accounted for 49% of the variance in treatment
      response, was statistically significant (P < .0001), and correctly predicted
      treatment outcome for 41 of 47 subjects (87%) in the criterion group. The
      predictive utility of the identified items remained statistically significant
      when applied to the cross-validation group (P < .01). The discriminant function
      employing the items correctly predicted treatment outcome for 37 of 47 subjects
      (79%) and explained 28% of the variance in treatment response. Findings of this
      study suggest that pretreatment psychosocial information is important in
      predicting treatment outcome for chronic temporomandibular disorders, and that
      symptoms of depression mediate treatment response for chronic pain patients.

PMID- 8995918
TI  - Reasons that patients do not return for appointments in the initial phase of
      treatment of temporomandibular disorders.
AB  - Patients suffering form pain and dysfunction in the temporomandibular region
      sometimes ignore appointments after the initial examination. This from of
      noncompliance is well known and is often studied in patients suffering from
      recurrent headaches, arthritis, and lower back pain. Information on patients with
      temporomandibular disorders (TMD) who fail to attend the next visits and do not
      comply with the proposed treatment is scare. To 61 patients (aged 20 to 40 years)
      who did not attend the next visit after an initial examination and after
      discussing the treatment protocol, a questionnaire was mailed 6 months to 1 year
      after the first visit. The questions related to reasons for not attending and the
      possible treatment received. Some questions were also related to the present TMD
      state. The clinical profiles of the nonattenders were compared to those of a
      group of 400 TMD patients who did finish the proposed treatment (positive
      control). The nonattenders had more pain and dysfunction at initial examination
      than did the treated patients. The treated patients reported a shorter duration
      of symptoms before seeking treatment than did the nonattenders suggesting that
      the latter group had a more chronic pain state. The main reason for not returning
      was that symptoms improved enough or disappeared completely and spontaneously
      without the proposed treatment. Sixteen patients did not return for further
      treatment for reasons linked to the dentist-patient relationship. Fifty-seven
      percent of the nonattenders reported to be symptom free or sufficiently improved.
      One year after the initial examination and without the proposed treatment, most
      still had some symptoms such as clicking (59%) and reduced mouth opening (21%),
      but only 24% reported to be in need of treatment.

PMID- 8995919
TI  - Lyme disease: considerations for dentistry.
AB  - Although Lyme disease has spread rapidly and it is difficult to diagnose, a
      review of the dental literature does not reveal many references to this illness.
      Dental practitioners must be aware of the systemic effects of this often
      multiorgan disorder. Its clinical manifestations may include facial and dental
      pain, facial nerve palsy, headache, temporomandibular joint pain, and masticatory
      muscle pain. The effects precipitated when performing dental procedures on a
      patient with Lyme disease must also be considered. This study discusses the
      epidemiology and diagnosis of Lyme disease, its prevention, and factors to
      consider when making a differential diagnosis. Dental care of the patient with
      Lyme disease and currently available treatments also are considered. Three case
      reports are presented.

PMID- 8995920
TI  - The flight from science and reason.

PMID- 8995921
TI  - Neuropeptides in the arthritic TMJ and symptoms and signs from the stomatognathic
      system with special consideration to rheumatoid arthritis.
AB  - The contribution of the nervous system to the pathophysiology of rheumatoid
      arthritis has been proposed to be mediated by certain neuropeptides. Neuropeptide
      Y, calcitonin gene-related peptide, substance P, and neurokinin A are considered
      modulators of inflammatory joint disease. Parameters of pain, as well as occlusal
      signs of tissue destruction from the arthritic TMJ and the corresponding
      neuropeptide concentrations in TMJ synovial fluid, were investigated in patients
      with various inflammatory joint diseases. The patients with rheumatoid arthritis
      were also examined in a separate diagnostic group. Visual analog scale, palpatory
      tenderness, maximal voluntary mouth opening, and anterior open bite were
      correlated to neuropeptide-like immunoreactivities of the above four
      neuropeptides. It was found that high concentrations of calcitonin gene-related
      peptide and neuropeptide Y in TMJ fluid are associated with pain, impairment of
      mandibular mobility, and occlusal signs of TMJ destruction in patients with
      rheumatoid arthritis. The results indicated neuropeptide involvement in
      rheumatoid arthritis, proposing a potentiation of the symptoms and signs by the
      inflammatory action of calcitonin gene-related peptide and neuropeptide Y.

PMID- 8995923
TI  - The relationship between muscle tenderness and craniomandibular disorders: a
      study of 35-year-olds from the general population.
AB  - Of a random sample of 345 subjects aged 35 years and drawn from the general
      population of Vasterbotten County, Sweden, 276 (80%) participated in an
      epidemiologic survey on muscle tenderness of the jaw, neck, shoulder, arm, hand,
      and calf, and on the prevalence of signs and symptoms of craniomandibular
      disorders. The control group consisted of 144 subjects (52%) who had no
      tenderness. The remaining subjects were separated into groups: (1) 59 subjects
      (21%) with tenderness only in jaw muscles; (2) 26 subjects (9%) with tenderness
      only in neck/shoulder muscles; (3) 39 subjects (14%) with tenderness in muscles
      of the jaw and neck/shoulder; and (4) eight subjects (3%) with tenderness in all
      palpated muscles of the neck, shoulder, arm, hand, and calf. Women were found to
      have palpation tenderness significantly more often than men (P < .05). The main
      finding of this study was the presence of a significantly higher proportion of
      signs and symptoms of craniomandibular disorders in the group who had both jaw
      muscle tenderness and neck/shoulder muscle tenderness and in the group who had
      generalized tenderness than in the control group. The results indicate that in
      epidemiologic and clinical research of craniomandibular disorders, a distinction
      between local, regional, and general tenderness should be made since the etiology
      may differ.

PMID- 8995922
TI  - Epidemiology of research for temporomandibular disorders.
AB  - A systematic review was performed in response to a request by the National
      Institute of Dental Research to evaluate in broad terms the strength of evidence
      regarding therapy for temporomandibular disorders (TMD). This report describes
      the epidemiology of research for TMD in broad terms indicating the total number
      of citations, the proportion related to therapy, and the distribution according
      to study design and language or country of origin. Medline and hand searching of
      article bibliographies and of selected journals produced the set of citations
      evaluated. From 1980 to 1992, there were more than 4,000 references to TMD, of
      which about 1,200 regarded therapy. Forty-one percent of the 1,200 references
      were classified as reviews and only 15% were clinical studies. Less than 5% (n =
      51) were randomized controlled trials. This review identified a vast amount of
      literature on TMD with articles published in several different languages,
      indicating a worldwide interest in this problem. Because assimilation of this
      literature cannot be expected of the average practitioner treating patients who
      have TMD, or of most researchers in this area, it is likely not being used to its
      maximum potential. The literature on therapy for TMD consists primarily of
      uncontrolled observations of patients such as uncontrolled clinical trials, case
      series, case reports, and simple descriptions of techniques. It is generally
      agreed that such uncontrolled observations, while contributing to knowledge about
      therapy of TMD, are subject to considerable bias and thus difficult to interpret.
      If treatment of TMD is going to follow the trend in medicine to base patient-care
      decisions on evidence rather than expert opinion or pathophysiologic rationales,
      then more rigorously controlled clinical trials of most therapies will be
      necessary.

PMID- 8995924
TI  - Clinical diagnosis compared with findings of magnetic resonance imaging in 242
      patients with internal derangement of the TMJ.
AB  - The aim of this study was to compare the provisional diagnosis based on an
      initial clinical examination with subsequent findings of magnetic resonance
      imaging in patients with internal derangement of the temporomandibular joint.
      Clinical examinations were conducted on 242 patients (198 women and 44 men) who
      had unilateral (51%) or bilateral (49%) temporomandibular joint internal
      derangement. They were divided into the following categories: (1) disc
      displacement with reduction; (2) disc displacement without reduction; (3) "stuck"
      disc; (4) degenerative arthrosis with or without one of the above; and (5) normal
      temporomandibular joint of the contralateral side. There was no statistically
      significant difference in the distribution of disorders on a unilateral or
      bilateral basis or in the prevalence of disorders in right versus left joints.
      Based on the high occurrence of matching true-negative data, this study showed a
      highly statistically significant correlation between the magnetic resonance
      findings and the clinical data for all categories of derangement. Despite this
      high correlation, the magnetic resonance imaging and clinical diagnoses matched
      exactly in only 287 of the 484 joints studied. There was only partial agreement
      in the remaining 197 joints. The best clinical diagnosis in relation to the
      magnetic resonance findings was observed in the arthrosis category followed by
      the categories of normal joint, disc displacement with reduction, stuck disc, and
      disc displacement without reduction, in descending order. This study strongly
      suggests that degenerative arthrosis is a result of a long-term displaced disc.
      The clinical examination alone did not correctly indicate all the structural
      defects; therefore, it is insufficient for determining the status of the joint.

PMID- 8995925
TI  - Electronic facial thermography: an analysis of asymptomatic adult subjects.
AB  - Vascular heat emissions that present on the human face can provide physiologic
      indicators of underlying health or disease. Electronic thermography may serve as
      a nonionizing, noninvasive alternative for solving diagnostic problems. This
      study was designed to quantify normal values of vascular heat emissions of the
      face. Electronic thermograms were taken of 102 subjects using an Agema 870 unit,
      at 0.1 degree C accuracy, under controlled conditions. Results indicated a high
      degree of mean thermal symmetry about the face. Using frontal and lateral
      electronic thermogram projections, the mean temperatures of 25 selected right
      versus-left-side anatomic zones were within 0.1 degree C of each other. Analysis
      of frontally and laterally projected electronic thermograms also produced a new
      mapping of thermally distinct facial zones. Of greatest importance, the right
      versus-left-side thermal differences (delta T) between many specific facial
      regions for individual subjects were demonstrated to be much smaller (< 0.4
      degrees C) than previously reported delta T values of the same facial regions in
      a wide variety of chronic disorders. These differences in delta T values between
      asymptomatic subjects and patients with various facial pain syndromes may prove
      to be useful thresholds for determining normal versus abnormal facial
      thermograms.

PMID- 8995926
TI  - The degree to which dental attrition in modern society is a function of age and
      of canine contact.
AB  - Dental attrition ranked according to a validated severity scale correlated with
      age as a proxy for functional wear in 148 asymptomatic subjects. Anterior,
      posterior, mediotrusive, laterotrusive, and total attrition severity was
      analyzed. The geometric contribution of canine attrition to the variance of
      posterior attrition was also tested through correlations, and the time span
      required to record a statistically significant difference in attrition using the
      scale was determined. Age explained 12.6% of the differences the total attrition
      scores (P < .001, Spearman's rho), 6.4% of the anterior scores (P < .01), and
      20.9% of the laterotrusive scores (P < .0001). Canine wear in subjects aged 20 to
      49 years explained between 20% to 34% of the posterior attrition (P < .05 to P <
      .001), 6% to 36% of the mediotrusive attrition (P < .05 to P < .01), and 20% to
      29% of the laterotrusive attrition (P < .05 to P < .001). At least 20 to 30 years
      was necessary to show significant clinical differences, except that laterotrusive
      attrition changes could be discriminated in only 10 years for the 20- to 29-year
      old group. Notable attrition was already evident in the 20- to 29-year-olds, and
      accelerated wear rates prior to age 20 years were not maintained in most areas of
      the dentition. A nonlinear progression with age was observed, thereby inhibiting
      prediction of subsequent attrition from prior levels. Attrition was concluded to
      have multifactorial etiology, with age and the geometry of canine guidance having
      a significant influence, in addition to commonly accepted parafunction.

PMID- 8995927
TI  - Benign indomethacin-responsive headaches presenting in the orofacial region:
      eight case reports.
AB  - Indomethacin-responsive headaches can present in the orofacial region. According
      to the classification of headache by the International Headache Society,
      indomethacin-responsive headaches include chronic paroxysmal hemicrania,
      hemicrania continue, benign cough headache, benign exertional headache, and
      sharp, short-lived headache pain syndrome. The mechanism by which indomethacin
      produces its therapeutic effects in these headache disorders remains speculative.
      A review of indomethacin-responsive headaches and eight cases in which the
      presenting symptom was orofacial pain are reported. Because these headache
      disorders are rare but may present as facial pain, they should be considered in
      the differential diagnosis of orofacial pain. A comprehensive evaluation prior to
      performing irreversible treatments is essential when an idiopathic facial pain
      presents to the dental clinician.

PMID- 8995928
TI  - Temporomandibular joint derangement with multiple surgical interventions: a case
      report.
AB  - This case report describes the experience of a 26-year-old woman who underwent
      multiple jaw surgeries. An initial 22 months of unsuccessful nonsurgical therapy
      was followed by a 7-year period during which the following were performed: 12
      surgeries of her right temporomandibular joint; one surgery of her left
      temporomandibular joint; bilateral coronoidectomies; one surgery of her right
      mandible; and three surgeries of her left mandible. This case is important
      because although the existence of multiple jaw surgery cases are widely noted
      throughout the literature, this is the first case report that presents in-depth
      prospective documentation.

PMID- 8995929
TI  - Barrett's esophagus: what do we really know about this disease?

PMID- 8995930
TI  - Extrahepatic manifestations of chronic viral hepatitis.

PMID- 8995931
TI  - Evaluation of pancreatic disease by endoscopic ultrasonography.

PMID- 8995932
TI  - The relationship between gastroesophageal reflux disease and its complications
      with Barrett's esophagus.
AB  - BACKGROUND: Barrett's esophagus is a condition in which the stratified squamous
      epithelium of the esophagus is replaced by a columnar epithelium with malignant
      potential. Chronic gastroesophageal reflux disease (GERD) is accepted as the
      primary risk factor for the development of Barrett's esophagus, but only a small
      fraction of individuals with GERD develop Barrett's esophagus. We sought to
      identify factors that increase the risk of Barrett's esophagus in those with
      GERD. OBJECTIVE: The objective of this matched case-control study was to
      investigate possible clinical risk factors for Barrett's esophagus. METHODS: The
      study was based on 79 case patients with Barrett's esophagus and 180 control
      patients. Each case patient was matched to one control patient whose indication
      for endoscopy was GERD and one control patient who underwent endoscopy for other
      indications. The case and control patients were matched for age, gender, and
      race. All patients underwent endoscopy at Duke University Medical Center, Durham,
      NC, between July 1992 and August 1994. RESULTS: On average, patients with
      Barrett's esophagus developed reflux symptoms at an earlier age than age- and
      gender-matched control patients and also had a longer duration of symptoms.
      Complications of reflux, including esophagitis, stricture, and ulceration, were
      reported significantly more frequently in the group of case patients than either
      group of control patients. CONCLUSIONS: The results of this pilot study indicate
      that age of onset, duration of symptoms, and complications of GERD may be markers
      of increased risk of Barrett's esophagus.

PMID- 8995933
TI  - Quantification of duodenogastric reflux in Barrett's esophagus.
AB  - OBJECTIVES: Our objective was to assess the role of reflux of duodenal contents
      in the genesis of Barrett's esophagus. Therefore, we performed a study to
      quantify duodenogastric reflux, using 99mTc-HIDA quantification in gastric juice
      after continuous intravenous infusion of the same. METHODS: The study contained
      20 patients with Barrett's esophagus (10 uncomplicated and 10 complicated by
      ulcers and/or stenosis), 10 patients with peptic esophagitis without Barrett's
      esophagus (two grade I, four grade II, and four grade III, according to Savary
      Miller), and 10 healthy volunteers who made up the control group. Comparisons
      were made between the groups. RESULTS: When we considered the groups overall, we
      observed that the 20 patients with Barrett's esophagus had higher reflux rates (p
      < 0.01) than either the 10 patients with peptic esophagitis without Barrett's
      esophagus, or the 10 controls. Complicated Barrett's esophagus presented higher
      reflux rates than uncomplicated Barrett's esophagus, although the differences
      were not statistically significant. However, on analyzing the results after
      considering the groups case by case, we see that the mean reflux rate in the
      Barrett's esophagus groups is due to five patients presenting much higher rates
      than the rest. CONCLUSIONS: Our results suggest that duodenogastric reflux might
      be involved in the appearance of Barrett's esophagus and its related
      complications, although only in certain cases. The pathogenesis of Barrett's
      esophagus is probably multifactorial, and other factors must be involved.

PMID- 8995934
TI  - Natural course of gastroesophageal reflux disease: 17-22 year follow-up of 60
      patients.
AB  - OBJECTIVE: To elucidate the long-term course of conservatively managed
      gastroesophageal reflux disease without H2-antagonists or omeprazole. METHODS: 
      DESIGN: Clinical trial, uncontrolled. SETTING: Gastroenterological outpatient
      department of a teaching hospital. PATIENTS: Sixty of 87 patients consecutively
      referred for severe gastroesophageal reflux symptoms and with objectively proven
      pathological reflux. MEASUREMENTS: Esophagoscopy, esophagography,
      cinecardiography of cardiac region, standard reflux test, and confirmatory
      Bernstein-Baker test. Follow-up included a standardized interview, esophagoscopy
      with biopsy, and 24-h pH monitoring. RESULTS: At follow-up 17-22 yr after
      referral, symptoms were less than at the time of referral in 36 of the 50
      nonoperated patients (six now symptom-free), were unchanged in five, and were
      worse in nine patients. Medication for reflux symptoms was no longer used by 34
      of the nonoperated patients. The prevalence of erosive esophagitis fell from 40%
      at referral to 27% at follow-up endoscopy; 42% of the studied patients had
      pathological 24-h pH, and the endoscopies revealed six new cases of Barrett's
      metaplasia. Of the 41 nonoperated patients examined with both endoscopy and 24-h
      pH, 27 (66%) had erosive esophagitis and/or pathological pH values. Of the 10
      operated patients, all had fewer symptoms at follow-up than they had at referral
      (nine were symptom-free). The prevalence of erosive esophagitis fell from 60% at
      referral to 10% at follow-up. One of the 10 patients had pathological 24-h pH at
      follow-up. Neither the presence of esophagitis or hiatal hernia nor the severity
      of symptoms at the time of referral predicted the course of the disease of the
      conservatively treated patients. CONCLUSIONS: The severity of the symptoms
      declines in the long term, but pathological reflux persists in most of the
      conservatively treated patients. Thus, the reflux itself is not self-limiting,
      and therapy should be designed with this in mind.

PMID- 8995935
TI  - Hemorrhage in the upper gastrointestinal tract in the older patient.
AB  - OBJECTIVE: To characterize the natural history of bleeding in the upper GI tract
      in the older age patient. METHODS: We retrospectively reviewed data on 200
      patients admitted with the diagnosis of upper GI bleeding (100 consecutive
      patients less than 60 yr of age and 100 consecutive patients more than 60 yr of
      age). Information collected included historical features of presentation,
      physical examination findings, laboratory data, endoscopic findings, and length
      of hospital stay. Results were analyzed using X2 and Student's tests. RESULTS:
      Upon presentation, fewer patients over 60 had a history of alcohol consumption
      (29 vs 65 patients, p < 0.05). They also had significantly less dyspepsia (49 vs
      64 patients, p < 0.05). Findings at endoscopy included more ulcer disease in the
      older patients (duodenal or gastric ulcer in 73 vs 48 patients, p < 0.05) and
      more acid peptic disease as well (duodenal ulcer, gastric ulcer, duodenitis,
      gastritis, or esophagitis in 91 vs 70 patients, p < 0.05). Younger patients had
      more Mallory-Weiss tears (14 vs three patients, p < 0.05) and a trend toward more
      variceal bleeds (19 vs 11 patients; p = 0.39). The hospital course in the two
      groups was not different with regard to the need for intensive care (61 patients
      under 60 vs 54 patients over 60), number of patients rebleeding (13 patients
      under 60 vs 15 patients over 60), mean number of blood units transfused (4 units
      in each group), mean duration of hospital stay (5.6 days in patients under 60 vs
      6.0 days in patients over 60), or mortality (six patients in each group).
      CONCLUSIONS: Compared with younger patients, patients 60 yr of age and older
      admitted to the hospital for upper GI bleeding are less likely to have a history
      of alcohol consumption or dyspepsia. They do have a greater likelihood of peptic
      disease, which accounts for their bleeding. Patients aged 60 yr and older do not
      have a significantly different hospital course from that of patients less than 60
      yr old with regard to need for intensive care, transfusion requirements, duration
      of hospital stay, or mortality.

PMID- 8995936
TI  - Small intestinal bacterial overgrowth in the symptomatic elderly.
AB  - OBJECTIVE: 1) To determine the prevalence of small intestinal overgrowth with
      colonic-type bacteria in symptomatic elderly subjects, particularly those without
      important "clues" such as clinically apparent predisposition or vitamin B12
      deficiency, and 2) to investigate defense mechanisms such as gastric acidity,
      small intestinal motility, and luminal IgA in this setting. METHODS: Fifty-two
      symptomatic subjects without vitamin B12 deficiency or clinically apparent
      predisposition to bacterial overgrowth or disturbed mucosal immunity, including
      22 subjects > or = 75 yr old, underwent culture of small intestinal luminal
      secretions. Indicator paper was used to measure fasting gastric pH. The presence
      of bacteria of confirmed nonsalivary origin in small intestinal secretions served
      as an index of small intestinal dysmotility. Small intestinal luminal IgA
      concentrations were measured by radial immunodiffusion. RESULTS: Small intestinal
      overgrowth with colonic-type flora was not present in any subject investigated
      for dyspepsia, irrespective of age. In subjects with chronic diarrhea, anorexia,
      or nausea, overgrowth with colonic-type flora (Enterobacteriaceae) was present in
      0/12 (0%), 1/10 (10.0%), and 9/14 (64.3%) subjects aged < 50 yr, 50-74 yr, and >
      or = 75 yr, respectively. Enterobacteriaceae were not concurrently recovered from
      saliva of any subject > or = 75 yr old with small intestinal overgrowth with
      these bacteria. Fasting hypochlorhydria was present in only 1/9 (11.1%) such
      subjects. Luminal IgA concentrations were significantly greater in subjects > or
      = 75 yr old with bacterial overgrowth than in culture-negative subjects (p < or =
      0.003). CONCLUSIONS: Small intestinal overgrowth with colonic-type bacterial
      should be considered in subjects > or = 75 yr old with chronic diarrhea,
      anorexia, or nausea, even in the absence of clues such as clinically apparent
      predisposition or vitamin B12 deficiency. Small intestinal dysmotility, rather
      than fasting hypochlorhydria or mucosal immunosenescence, probably is responsible
      for the prevalence of bacterial overgrowth in this group.

PMID- 8995937
TI  - Association of esophagitis and esophageal strictures with diseases treated with
      nonsteroidal anti-inflammatory drugs.
AB  - BACKGROUND: It has been speculated that intake of nonsteroidal anti-inflammatory
      drugs (NSAIDs) represents a risk factor for the occurrence of esophagitis and
      esophageal strictures. METHODS: A case-control study was conducted to compare the
      occurrence of comorbid diseases treated with NSAIDs in case and control subjects
      with and without esophageal disease, respectively. The case population was
      comprised of all patients with esophagitis (International Classification of
      Diseases code 530.1) or esophageal stricture (code 530.3) who were discharged
      from hospitals of the Department of Veteran Affairs between 1981 and 1994. In
      separate multivariate logistic regressions, the occurrence of esophagitis or
      esophageal stricture served as the outcome variable, and age, gender, ethnicity,
      and comorbid occurrence of an NSAID-related diagnosis served as modifier
      variables. RESULTS: A total of 101,366 individual case subjects were included, of
      whom 92,860 presented with esophagitis and 14,201 with stricture. The occurrence
      of erosive esophagitis was associated with osteoarthritis (odds ratio = 1.42, 95%
      confidence interval = 1.36-1.48), osteoporosis (1.38, 1.25-1.52), back pain
      (1.49, 1.42-1.56), femur bone fracture (1.46, 0.92-2.32), fibrositis (1.57, 1.41
      1.75), tension headache (1.34, 1.27-1.40), ankylosing spondylitis (1.33, 1.24
      1.42), rheumatoid arthritis (1.13, 1.05-1.21), sicca syndrome (1.15, 1.05-1.26),
      and systemic sclerosis (6.16, 4.65-8.14). NSAID-related diagnoses represented
      similar risk factors for both esophagitis and esophageal stricture. CONCLUSIONS:
      A large variety of diseases treated by NSAIDs are associated with a significantly
      increased risk of esophageal erosion or stricture; the risk appears similar for
      both of these. In some comorbid conditions, the underlying disease process may
      contribute to the occurrence of esophageal pathology.

PMID- 8995938
TI  - Collagenous colitis: histopathology and clinical course.
AB  - OBJECTIVES: Collagenous colitis is a chronic diarrheal disease characterized by a
      normal or near-normal mucosa endoscopically and microscopic inflammation in the
      lamina propria, surface epithelial injury and a thick subepithelial collagen
      layer. The symptoms of collagenous colitis vary in duration and intensity, and
      long periods of remission have been described, but long-term follow-up data are
      limited. Our goal was to determine the natural clinical history of collagenous
      colitis and to determine whether there was a relationship between histopathologic
      changes and course of disease. METHODS: Cases were identified at the University
      of Michigan Hospitals using surgical pathology records before 1992. All charts,
      including medical records from other hospitals, were reviewed, and a telephone
      interview was conducted with each locatable patient (pt). Biopsy specimens were
      reviewed by two pathologists for degree of collagen layer thickness, epithelial
      damage, and inflammation. RESULTS: There were 31 patients (26 F, 5 M) with a mean
      age of 66 yr (range 33-83) and a mean duration of symptoms of 5.4 yr at the time
      of diagnosis. Of the 31 patients, 18 (56%) had some form of arthritis, and 22
      (71%) were using NSAIDS regularly at the time of diagnosis. Follow-up interviews
      were conducted at least 2 yr after diagnosis (mean 3.5 yr, range 2-5 yr) with 27
      of 31 patients (3 could not be located, 1 died). Two definable groups of patients
      were identified: (1) those with either spontaneous or treatment-related symptom
      resolution (63%), and (2) those with ongoing or intermittent symptoms requiring
      at least intermittent therapy (37%). There was no significant difference between
      the two groups with regard to sex, age, associated diseases, and use of
      medications. Patients with symptom resolution (mean duration 3.1 yr) had been
      treated with antidiarrheals (6), sulfasalazine (3), discontinuation of NSAIDS
      (3), reversal of jejunoilial bypass (1), or nothing (4). Those with ongoing
      symptoms experienced a wide range of symptom severity. Two required only
      antidiarrheals, but five required or failed steroids, azathioprine, or
      sandostatin. There was no significant difference in collagen thickness,
      epithelial damage, and inflammation between the two groups, but Paneth cell
      metaplasia was seen more often in those with ongoing symptoms. In 24 of 27
      patients, diagnostic changes were present in left-sided biopsies. CONCLUSIONS: In
      our cohort of patients, 63% had lasting resolution of symptoms after a mean 3.5
      yr follow-up. There was a high incidence of arthritis and NSAID use in our
      population, but there was no relationship between these entities and clinical
      course or histology. Initial histology, except possibly for Paneth cell
      metaplasia, did not reliably predict severity or course of disease. Finally,
      although variable in clinical presentation, treatment-free remissions are common
      in collagenous colitis.

PMID- 8995939
TI  - Early loss of serum hepatitis C virus RNA can predict a sustained response to
      interferon therapy in patients with chronic hepatitis C.
AB  - OBJECTIVES: We evaluated whether the loss of serum hepatitis C virus (HCV) RNA
      early in interferon (IFN) therapy would indicate a subsequent response to IFN
      therapy. METHODS: One hundred fourteen patients with chronic hepatitis C were
      treated with IFN-alpha for 24 weeks. All patients were positive for anti-HCV
      antibodies and serum HCV RNA. Serum HCV RNA was measured by highly sensitive and
      specific RT-PCR (modified Amplicor HCV). RESULTS: Of 114 patients who were
      treated with IFN-alpha for 24 weeks, 22 of 29 patients (75.9%) who lost HCV RNA
      at the first week of treatment, 5 of 14 patients (35.7%) who lost HCV RNA at the
      second week, and 2 of 16 patients (12.5%) who lost HCV RNA at fourth week were
      judged as sustained responder (SR). The SR rate was significantly higher in
      patients who lost HCV RNA at the first week of therapy (p < 0.05). On the
      contrary, none of 55 patients who retained HCV RNA during the first 4 weeks of
      IFN therapy were judged as SR. Concerning the patients who lost HCV RNA at the
      first week of therapy, there were no significant differences in the SR rate in
      either HCV genotype (1b, 2a, and 2b). CONCLUSIONS: Our study confirms that the
      early response to IFN (loss of HCV RNA at the end of the first week of IFN
      therapy) can be a predictor of the subsequent sustained response to IFN therapy.
      Additionally, positivity of HCV RNA at the fourth week of IFN therapy can be a
      predictor of the subsequent nonsustained response to IFN therapy.

PMID- 8995940
TI  - Long course and prognostic factors of virus-induced cirrhosis of the liver.
AB  - OBJECTIVE: Chronic infection by hepatitis B virus (HBV) and hepatitis C virus
      (HCV) is now recognized as a major cause of liver cirrhosis. This study was aimed
      at evaluating the natural history of the disease in a large series of Italian
      patients with HBV- and HCV-related cirrhosis without portal hypertension at
      entry. METHODS: The clinical records of 405 patients (233 males, mean age 54 +/-
      9 yr) with histologically proven cirrhosis (321 with HCV-related and 84 with HBV
      related cirrhosis) and no clinical evidence of portal hypertension at entry were
      retrospectively examined to evaluate the occurrence of complications and the
      cumulative mortality rate during follow-up. RESULTS: Patients had a mean follow
      up of 8 +/- 3 yr. The cumulative survival rate was 99.1% at 5 yr, 76.8% at 10 yr,
      and 49.4% at 15 yr. The age-adjusted death rate was 3.14 and 2.84 times higher
      than in the general Italian population in men and women, respectively. Only the
      bilirubin level was an independent indicator of survival. Esophageal varices,
      ascites, jaundice, hemorrhage, hepatic encephalopathy, and hepatocellular
      carcinoma significantly reduced the survival rate (major complications), whereas
      thrombocytopenia, diabetes, and cholelithiasis did not affect survival (minor
      complications). The incidence of hepatocellular carcinoma was similar in patients
      with either HBV- or HCV-related disease and was quite frequent, especially in
      males. CONCLUSIONS: This study demonstrates that the course of virus-induced
      liver cirrhosis is not influenced by the etiology of the disease and that the
      occurrence of complications significantly shortens life expectancy. The longer
      survival rate observed in this study is probably due to the fact that cirrhosis
      was here recognized by liver biopsy in the absence of clinical evidence of portal
      hypertension.

PMID- 8995941
TI  - Patterns of hepatitis C viremia in patients receiving hemodialysis.
AB  - OBJECTIVES: Chronic hepatitis C virus (HCV) infection is common in patients who
      receive hemodialysis (HD). The aim of this study was to determine the natural
      history of hepatitis C viremia and the clinical utility of quantitation and
      genotyping of HCV in this population of patients. METHODS: Consecutive sera from
      two groups of HD patients who were HCV RNA positive, a group of 33 patients
      treated with interferon alfa (5 MU, three times a week for 4 months) and a group
      of 31 untreated patients, were analyzed by qualitative polymerase chain reaction,
      quantitative polymerase chain reaction, and a line probe assay for genotyping.
      RESULTS: Serum HCV RNA was detected continuously in 20 of 31 untreated patients
      (65%), and 11 patients (35%) showed a fluctuating pattern of viremia with virus
      free intervals of up to 4 wk. Twenty-five of 33 patients (76%) treated with
      interferon alfa became HCV RNA negative during therapy; eight of these 25
      patients had a breakthrough, which was transient in seven patients and persistent
      in one. Of the remaining 24 end-of-treatment responders, 17 relapsed after
      completion of therapy, and seven (21%) had a sustained response with undetectable
      serum HCV RNA for 1 yr of follow-up. Initial serum HCV RNA levels in HD patients
      were generally low (median, 1 x 10(5) genome eq/ml). Sustained responders had
      significantly lower median levels of viremia (4 x 10(4) eq/ml) than relapsers and
      nonresponders (9 x 10(4) and 1.8 x 10(5) eq/ml, respectively). Genotyping
      revealed a predominance of genotype 1a (33%) and 1b (48%). CONCLUSIONS: This
      study documents that fluctuating hepatitis C viremia with periods of undetectable
      HCV RNA is common and that low viral load predicts a sustained response to
      interferon therapy in HD patients. Diagnosis of chronic hepatitis C and
      monitoring of interferon therapy in HD patients should include initial HCV RNA
      quantitation and repeated qualitative measurements of HCV RNA.

PMID- 8995942
TI  - Nasogastric omeprazole: effects on gastric pH in critically Ill patients.
AB  - OBJECTIVE: The efficacy of omeprazole administered by the nasogastric route has
      not been adequately studied. We sought to determine whether nasogastrically
      administered omeprazole could effectively maintain an intragastric pH greater
      than 4.0 in patients hospitalized in a medical intensive care unit. METHODS:
      Patients were considered eligible for the study if they had a nasogastric feeding
      tube in place and had not received omeprazole, antacids, or histamine-2 blockers
      in the 5 days preceding study enrollment. Exclusionary criteria included active
      GI bleeding or a mean baseline gastric pH greater than 4.0. Patients served as
      their own controls during a 24-h lead-in period, during which baseline
      intragastric pH was measured by gastric aspirate. Omeprazole, 20 or 40 mg, was
      administered once daily with water through a nasogastric tube. Intragastric pH
      was measured every 4-8 h for a maximum of 3 days following drug administration.
      RESULTS: Twenty patients were considered eligible for the study; 10 were excluded
      because of an elevated baseline gastric pH (n = 8) or because proper gastric
      aspirates could not be obtained (n = 2). The mean baseline intragastric pH in
      four patients receiving omeprazole 20 mg q.d. was 2.4 +/- 1.1 and increased to
      3.7 +/- 1.6 after drug administration (p = 0.013). The mean baseline intragastric
      pH in six patients receiving omeprazole 40 mg q.d. was 2.8 +/- 0.8 and increased
      to 5.7 +/- 1.1 after drug administration (p < 0.001). The percentage of
      intragastric pH values greater than 4.0 after drug administration was 34.2% in
      patients receiving omeprazole 20 mg q.d. and 84.7% in those receiving omeprazole
      40 mg q.d. CONCLUSIONS: Nasogastric omeprazole 40 mg q.d. is effective in
      maintaining an intragastric pH greater than 4.0 in critically ill patients. The
      nasogastric administration of omeprazole offers a cost-effective therapeutic
      option for acid suppression in patients at risk for stress mucosal ulceration.

PMID- 8995943
TI  - Percentage changes in serum pepsinogens are useful as indices of eradication of
      Helicobacter pylori.
AB  - OBJECTIVE: Eradication of Helicobacter pylori has been gaining significance for
      the treatment of gastroduodenal diseases. Establishment of a precise diagnostic
      method for H. pylori is of great value. The aim of this study was to establish a
      new method for precisely judging the eradication of this bacteria. METHODS: We
      measured serum pepsinogen I (PG I) and pepsinogen II (PG II) levels in 105 cases
      of peptic ulcer with H. pylori infection before and after anti-H. pylori
      treatment, determined percentage changes in serum PG I:PG II ratios before and 1
      month after the treatment, and established cut-off values for them to distinguish
      success from failure of H. pylori eradication. Cut-off values for percentage
      changes in serum PG I:PG II ratios were tentatively set as +40%, +25%, and +10%
      when the serum PG I:PG II ratios before treatment were less than 3.0, not less
      than 3.0 but less than 5.0, and not less than 5.0, respectively. RESULTS: With
      these cut-off values, the sensitivity, specificity, and validity for
      determination of eradication of H. pylori-on the basis of culture, histology, the
      rapid urease test, and a polymerase chain reaction method-were 100.0%, 93.1%, and
      96.2%, respectively. These cut-off values could be applied to both gastric ulcer
      and duodenal ulcer. CONCLUSION: Our findings suggest that percentage changes in
      serum PG I:PG II ratios are useful as indices for distinguishing success from
      failure in eradication therapy for H. pylori.

PMID- 8995944
TI  - Influence of a methanogenic flora on the breath H2 and symptom response to
      ingestion of sorbitol or oat fiber.
AB  - BACKGROUND AND OBJECTIVES: We investigated the possibility that a variant of the
      normal colonic flora, a high concentration of methanogens, influences the host's
      response to ingestion of nonabsorbable, fermentable materials. METHODS: To better
      evaluate symptomatic and breath H2 and methane (CH4) responses, subjects were
      placed on a basal diet (primarily rice and hamburger) that contained minimal
      amounts of nonabsorbable, fermentable substrate. A breath CH4/H2 ratio of greater
      or less than 1 on the second day of the basal diet was used to categorize
      subjects as high (N = 9) or low (N = 25) CH4 producers. After stabilization of
      the breath gas excretion (day 3 or 4 on the basal diet), the subjects ingested
      either sorbitol (8.8 g) or oat fiber (10.2 g). RESULTS: The low CH4 producers had
      a significantly higher (p < 0.05) breath H2 concentration than the high producers
      on the basal diet and after ingestion of sorbitol (27.1 +/- 2.7 ppm vs 15.8 +/-
      3.6 ppm) or oat fiber (13.1 +/- 0.08 ppm vs 9.6 +/- 1.2 ppm). Low producers of
      methane reported significantly increased bloating and cramping after sorbitol
      ingestion and increased bloating after fiber ingestion, whereas high CH4
      producers reported no significant increase in these symptoms. CONCLUSION: The
      presence of a methanogenic flora is associated with a reduced symptomatic
      response to ingestion of nonabsorbable, fermentable material in healthy subjects.
      Manipulation of the normal flora could be of therapeutic value in nonmethanogenic
      patients with irritable bowel syndrome.

PMID- 8995945
TI  - Clinical response to dietary fiber treatment of chronic constipation.
AB  - OBJECTIVES: To determine the clinical outcome of dietary fiber therapy in
      patients with chronic constipation. METHODS: One hundred, forty-nine patients
      with chronic constipation (age 53 yr, range 18-81 yr, 84% women) at two
      gastroenterology departments in Munich, Germany, were treated with Plantago ovata
      seeds, 15-30 g/day, for a period of at least 6 wk. Repeated symptom evaluation,
      oroanal transit time measurement (radiopaque markers), and functional rectoanal
      evaluation (proctoscopy, manometry, defecography) were performed. Patients were
      classified on the basis of the result of dietary fiber treatment: no effect, n =
      84; improved, n = 33; and symptom free, n = 32. RESULTS: Eighty percent of
      patients with slow transit and 63% of patients with a disorder of defecation did
      not respond to dietary fiber treatment, whereas 85% of patients without a
      pathological finding improved or became symptom free. CONCLUSION: Slow GI transit
      and/or a disorder of defecation may explain a poor outcome of dietary fiber
      therapy in patients with chronic constipation. A dietary fiber trial should be
      conducted before technical investigations, which are indicated only if the
      dietary fiber trial fails.

PMID- 8995946
TI  - Pectin and methyl cellulose do not affect intestinal function in patients after
      ileal pouch-anal anastomosis.
AB  - OBJECTIVES: Although ileal pouch-anal anastomosis is the procedure of choice for
      most patients with ulcerative colitis or familial adenomatous polyposis, most
      patients have problems with stool frequency and/or consistency. Although most
      clinicians recommend fiber supplementation for these patients, we could find no
      studies that prove the efficacy of this practice. The first purpose of this study
      was to document the effect of fiber supplementation on intestinal function in
      patients after ileal pouch-anal anastomosis. Because pectin, a soluble fiber
      supplement, has been reported to slow gastric and intestinal transit, we also
      hypothesized that pectin would be a superior fiber supplement in these patients.
      The second purpose, therefore, was to determine whether the effects of pectin on
      intestinal transit would result in decreased stool frequency in patients with an
      ileal pouch. METHODS: Thirteen patients who had undergone ileal pouch-anal
      anastomosis for ulcerative colitis were entered into a 9-wk crossover study. The
      protocol consisted of three 2-wk study periods, each of which was preceded by a 1
      wk washout period. During the three study periods patients supplemented their
      diets, in random order, with Citrucel, 1 tablespoon twice daily; pectin, 1
      tablespoon twice daily; or no supplement. Patients maintained detailed dietary
      and bowel function diaries. RESULTS: The effects (mean +/- SE) of Citrucel and
      pectin supplementation are summarized in Table 1. There was no significant effect
      of either supplement on stool frequency, pouch function, bloating, or stool
      consistency. In addition, there were no differences in continence. CONCLUSIONS:
      We found no evidence to support the common practice of fiber supplementation in
      patients with an ileal pouch. Furthermore, this study did not find that stool
      frequency decreased during supplementation with pectin. We conclude that there is
      little role for fiber supplementation in patients with an ileal pouch.

PMID- 8995948
TI  - Colorectal cancer after gastric surgery: a meta-analysis.
AB  - BACKGROUND: Until now, the question of whether previous gastric surgery results
      in an increased risk of colorectal cancer has remained controversial. A meta
      analysis was performed to resolve this issue. METHODS: The numbers of colorectal
      tumors in the two populations with and without gastric surgery were retrieved
      from all relevant articles found through a MEDLINE search. If available, the most
      detailed breakdown of the data by patient gender, type of peptic ulcer, type of
      surgery, time since gastric surgery, and by tumor location was chosen. The Mantel
      Haenszel procedure was used to calculate a weighted odds ratio from the
      individual studies. The method of DerSimonian and Laird was used to calculate a
      weighted average of the difference between tumor rates in patients with and
      without gastric surgery. RESULTS: The summary odds ratio was 1.09 with a 95%
      confidence interval of 0.96-1.24. The length of time after surgery, gender, tumor
      location, initial ulcer type, and different types of surgery were not associated
      with any significant influence. The summary rate difference was not significantly
      different from zero. The test for heterogeneity yielded a chi 2 = 26.87, df = 13,
      p = 0.013. After ignoring one obvious outlier study, the chi 2 test dropped to a
      nonsignificant level. A L'Abbe plot failed to show any prevailing influence of
      rate size on the overall heterogeneity among the various studies. CONCLUSIONS:
      Surgery for peptic ulcer does not result in an increased risk for colorectal
      tumors. This lack of influence was shown consistently by all tests of the present
      meta-analysis.

PMID- 8995947
TI  - Characterization of afferent mechanisms in ileoanal pouches.
AB  - OBJECTIVES: The afferent innervation of ileoanal pouches plays an important role
      in perception and in reflex regulation of pouch function. We aimed to
      characterize afferent nerve function in ileoanal pouches and thereby explain the
      clinical presentation of patients with such pouches. METHODS: In eight patients
      who underwent surgery for active ulcerative colitis, perception of balloon
      distention of the pouch was measured using an electronic visceral distention
      device. In addition, pouch compliance and ileoanal reflex function were
      determined. Studies were performed during the initial stage of pouch creation
      (pouch without connection to proximal ileum, study 1) and a mean of 6.6 wk (range
      = 2-12 wk) after the second stage of the surgery (proximal ileum in continuity
      with the pouch, study 2). Nine normal volunteers made up the control group.
      RESULTS: When expressed as intrapouch pressure, thresholds for stool and
      discomfort sensations were similar in patients with a pouch and controls.
      However, during ramp distention, patients with a pouch had a lower volume
      threshold for stool sensation (143 +/- 45 ml vs 300 +/- 30 ml, p = 0.009). The
      initial sensation of discomfort was experienced in the perineum at the S3
      dermatome in all eight patients. At higher distention pressures, all patients
      with a pouch referred sensations to the abdomen, as opposed to only one of nine
      controls with such a referral pattern (p < 0.0001). Pouch compliance was markedly
      reduced during study 1 but normalized after continuity was established with the
      proximal ileum. Anal sphincter function in patients with a pouch was similar to
      that in controls. CONCLUSIONS: Afferent pathways from both the ileum and rectum
      play a role in the mediation of sensations during mechanical distention of the
      ileoanal pouch and can explain a number of clinical features of patients with a
      pouch. The thresholds for activation of these pathways are not significantly
      altered by long-standing colorectal inflammation or by creation of the ileoanal
      pouch. Continuity with the proximal ileum significantly influences pouch
      compliance.

PMID- 8995949
TI  - Improved localizing method of radiopill in measurement of entire gastrointestinal
      pH profiles: colonic luminal pH in normal subjects and patients with Crohn's
      disease.
AB  - OBJECTIVE: To measure gastrointestinal (GI) pH profiles in patients with Crohn's
      disease with an improved pH radiotelemetry method. METHODS: A computer-assisted
      method was developed to exactly localize a pH sensitive radiotelemetry capsule
      (radiopill) in the GI tract from the stomach to the cecum by detecting distinct
      changes in transmitted pH signals sampled at 1-sec intervals. The combined usage
      of a radiodirectional probe facilitated localization of the radiopill in the
      colon. With this improved method, GI pH profiles in four patients (male/female,
      3/1; age range, 21-34 yr) with Crohn's disease that involved the left colon
      (active disease: 3; disease at quiescent state, 1) were measured and compared
      with those in four gender- and age-matched control subjects (controls). RESULTS:
      Gastric and small intestinal luminal pH profiles in Crohn's disease were similar
      to those in the controls. In contrast, colonic luminal pH profiles in both right
      (uninvolved) and left (involved) colon in active or quiescent Crohn's disease
      showed more coarse fluctuations with a significantly low value than those seen in
      the controls. The minimum colonic pH registered in the four patients was 0.6,
      1.2, 3.2, and 5.3 pH unit, respectively. The overall mean luminal pH (+/-SD) in
      the right colon was 5.3 +/- 0.3 for the patients versus 6.8 +/- 0.2 for the
      controls (p < 0.01) and that in the left colon was 5.3 +/- 0.7 versus 7.2 +/- 0.3
      (p < 0.01), respectively. CONCLUSION: This study first demonstrates that an
      extremely acidic colonic environment occurs in either active or inactive Crohn's
      disease.

PMID- 8995950
TI  - Low level hepatitis B viremia detected by polymerase chain reaction accompanies
      the absence of HBe antigenemia and hepatitis in hepatitis B virus carriers.
AB  - OBJECTIVES: Because outcome of antiviral treatment in patients with chronic
      hepatitis (CH) B is difficult to predict, we compared the severity of hepatitis
      with serum hepatitis B virus (HBV) DNA concentration. METHODS: We studied 40 HBV
      carriers with distinct stages of chronic infection, 32 HBe antigen (HBeAg)
      negative or low-grade positive carriers whose HBV strains did not contain a point
      mutation at nucleotide 1896, 37 HBeAg-negative carriers with or without
      hepatitis, and 51 HBeAg-positive CH patients treated with interferon. Serum HBV
      DNA concentration was measured by the end-point dilution method using a
      polymerase chain reaction (PCR). The point mutation at nucleotide 1896 was
      detected by restriction fragment length polymorphism with PCR. RESULTS: Among the
      stages of chronic HBV infection, the serum HBV DNA concentration was lowest
      (10(0.67 +/- 0.71) copies/microliter) in HBeAg-negative asymptomatic carriers. A
      low-level viremia (10(2.10 +/- 1.45) copies/microliter) of HBV strains without
      the mutation at nucleotide 1896 was associated with an HBeAg-negative state. In
      HBeAg-negative carriers, the serum HBV DNA concentration in those without
      hepatitis was significantly lower than in those with hepatitis (10(1.00 +/- 0.89)
      vs 10(3.31 +/- 1.25) copies/microliter, p < 0.0001); 20 of 21 asymptomatic
      carriers had an HBV DNA concentration below 10(2) copies/microliter. Patients
      with serum HBV DNA concentrations below 10(1) copies/microliter. at the end of
      interferon treatment maintained normal serum alanine aminotransferase
      concentrations. CONCLUSIONS: A serum HBV DNA concentration below 10(1) copies/
      microliter is an important goal for successful treatment of CH-B. PCR is
      necessary to assess such low-level viremias.

PMID- 8995951
TI  - A study of antimitochondrial antibodies in a random population in Estonia.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by
      the spontaneous destruction of the small intrahepatic bile ducts. The hallmark
      serologic feature of PBC is the presence of high-titer antimitochondrial
      antibodies (AMA). Both the incidence and prevalence of PBC varies geographically;
      epidemiological data may provide valuable insight regarding the pathogenic
      mechanisms and etiology of disease. Thus far, the majority of studies on the
      occurrence of PBC and AMAs have been derived from autopsy, mortality figures, or
      hospital admission records. The numbers reported reflect only those patients with
      clinical disease. To address this issue, an adult population sample representing
      all age groups in the village of Karksi-Nuia in southern Estonia was selected for
      a study of AMA incidence. This village has unique features that make it ideal for
      such a study. First, the village is remote and a substantial number of families
      have lived in the area for generations. There is also a limited influx of new
      families into the village, therefore providing a limited genetic repertoire. In
      this unselected adult population, we examined AMA incidence by both immunoblot
      and ELISA, using native and recombinant antigens. Of the 1461 people studied, 13
      (0.89%) were AMA positive. A similar frequency (0.96%) was found among 104
      persons from a neighboring village, who subsequently joined the study. Our study
      suggests that the presence of AMA in Estonia is in agreement with the reported
      incidence of less than 1% AMA in a mixed hospital population.

PMID- 8995952
TI  - Risk of asymptomatic and symptomatic gallstones in moderately obese women: a
      longitudinal follow-up study.
AB  - Obesity is a rather documented risk factor for the formation of gallstones (GS)
      in women. The magnitude of the increased risk and the rates of GS occurrence,
      however, have not been well quantified, except for two studies on the risk of
      symptomatic stones in obese women. We analyzed the incidence of GS in 157
      moderately obese women (body mass index, 31.4 +/- 3.6 kg/ m2) followed up
      prospectively by ultrasound for 2-6 yr (mean 3.95 yr). Women with morbid obesity
      (body mass index > 40 kg/m2) were excluded from the study, as well as patients
      having diseases with lithogenic risk. All the enrolled women had normal
      cholecystosonogram results at the beginning of the study. Age, family history of
      GS or obesity, parity, age of obesity onset, hyperlipoproteinemia type, plasma
      cholesterol (total, HDL, LDL), and triglycerides were assessed. The Student's t,
      the Mann-Whitney rank sum and the Fisher's exact tests were used, as well as the
      multiple logistic regression for the multivariate analysis. During the survey, 16
      of 157 women (10.2%) developed GS. GS were asymptomatic in 11 persons (68.8%).
      The cumulative incidence of both asymptomatic and symptomatic GS was 2.6
      cases/100 obese women.year. During the follow-up, most of the detected GS were
      asymptomatic, and this explains the higher GS incidence rate found compared with
      that previously calculated for symptomatic GS. The following risk factors were
      associated with GS formation: age (p = 0.002), family history of GS (p = 0.011),
      early obesity onset (p = 0.003), and hyperlipoproteinemia type IV (p = 0.011). A
      high risk class might be thus identified among obese women, offering a more
      realistic approach for the primary prophylaxis of GS.

PMID- 8995953
TI  - Causes and management of recurrent biliary pain after successful nonoperative
      gallstone treatment.
AB  - OBJECTIVE: To evaluate the frequency and causes of recurrent biliary colic after
      successful extracorporeal shock wave lithotripsy of gallstones. METHODS: Follow
      up of 77 patients for 2 yr (median) after complete gallstone clearance by
      lithotripsy and adjuvant oral litholysis. All patients with recurrent biliary
      colic were examined thoroughly (laboratory data, ultrasonography, gastroscopy);
      the examination included gallbladder motility testing. If the patients suffered
      from additional gastrointestinal complaints, further symptom-guided
      investigations (pH-metry, lactose absorption study, enteroclysis, colonic transit
      time, colonoscopy) were performed. Patients without documented gallstone
      recurrence underwent ERCP and sphincter of Oddi manometry. Cholecystectomy was
      advised for patients in whom gallstones recurred, and patients with sphincter of
      Oddi dysfunction underwent endoscopic sphincterotomy. If other gastrointestinal
      disorders were diagnosed, appropriate treatment was initiated. RESULTS: Twenty
      seven patients (35%) experienced biliary colic during follow-up. Gallstone
      recurrence was documented in 17 patients, and 16 of the patients who underwent
      cholecystectomy became symptom-free again (follow-up: 12 months). Gallbladder
      hypomotility was revealed in seven of the 17 patients with gallstone recurrence
      compared to none of the 10 patients without gallstone recurrence (p < 0.05).
      Microlithiasis was not detected in bile samples from the patients whose
      gallstones did not recur. Sphincter of Oddi dysfunction was found in four
      patients, and sphincterotomy cured all of them (follow-up: 9 months). Two of the
      remaining six patients had functional gastrointestinal disorders (reflux,
      constipation) and became asymptomatic after specific treatment. CONCLUSIONS:
      Biliary colic often recurs after successful gallstone lithotripsy. Recurrent
      gallbladder stones are the main cause, but another cause is sphincter of Oddi
      dysfunction. Neither gallbladder hypomotility nor microlithiasis seems to cause
      biliary symptoms in patients without recurrence of gallstones.

PMID- 8995954
TI  - Sjogren's syndrome with chronic pancreatitis, sclerosing cholangitis, and
      pulmonary infiltrations.
AB  - We report a patient with Sjogren's syndrome and multiple gastrointestinal
      manifestations who successfully responded to therapy with ursodeoxycholic acid.
      Our patient had sialoadenitis with dry mouth, dry eyes, arthralgia, chronic
      pancreatitis, sclerosing cholangitis, and pulmonary infiltrations. The first
      signs of disease were the symptoms of chronic pancreatitis followed by icterus,
      caused by extrahepatic bile duct obstruction. Sclerosing cholangitis was
      diagnosed by liver biopsy and endoscopic retrograde cholangiography.
      Sialoadenitis, causing dry mouth, was verified by buccal biopsy. Pulmonary
      infiltrations were seen on standard chest x-ray, and also shown by high
      resolution computed tomography examination. Obstructive icterus and even
      pulmonary infiltration responded successfully to treatment with ursodeoxycholic
      acid.

PMID- 8995955
TI  - Acute hepatitis and drug-related lupus induced by minocycline treatment.
AB  - Minocycline is widely prescribed for long-term treatment in acne. Major side
      effects are rare and include hepatitis and drug-related lupus. Hepatitis can be
      early and acute or late and chronic, whereas lupus presents as a tardive and
      insidious disease. We report a case of minocycline-induced lupus initially
      presenting as acute hepatitis, evolving to chronic cytolysis, in a young man
      treated for facial acne.

PMID- 8995956
TI  - Treatment of idiopathic lymphocytic enterocolitis with oral beclomethasone
      dipropionate.

PMID- 8995957
TI  - Hereditary megaduodenum.
AB  - Hereditary megaduodenum is a rare disease with autosomal dominant transmission
      characterized by visceral myopathy that involves the digestive and urinary
      tracts, and usually presents as intestinal pseudo-obstruction. Recently, a high
      rate of spontaneous chromosomal damage was found in blood lymphocytes of patients
      with hereditary megaduodenum, predictive of an increased cancer risk. Clinical
      manifestations of the disease vary, ranging from severe pseudo-obstruction to
      asymptomatic family members; recurrent urinary tract infections are common.
      Histology reveals vacuolar degeneration and fibrosis of the longitudinal layer of
      gastrointestinal muscle. This disease should be suspected in patients with an
      enlarged duodenum but no mechanical obstruction. Treatment is symptomatic and
      based on diet and control of bacterial overgrowth. Enteral or parenteral
      nutrition may be needed. Laterolateral duodenojejunostomy and gastrojejunostomy
      may sometimes be helpful to relieve obstructive symptoms. The risk of cancer in
      patients with hereditary megaduodenum is still unknown. This paper describes a
      family with hereditary megaduodenum in which one of the three affected members
      died of esophageal carcinoma and reviews the literature on the disease with
      particular attention to reports of cancer.

PMID- 8995958
TI  - Spectrum of mucus-secreting pancreatic neoplasia.
AB  - Mucus-secreting pancreatic lesions, most commonly described by the Japanese, are
      often malignant (as in cystic or mucin-producing adenocarcinomas), but can be
      benign (hyperplastic or adenomatous cytology). We report a case of total
      pancreatic ductal enlargement without a localized lesion in which abdominal pain
      was relieved by endoscopic sphincterotomy and partial septotomy in which cytology
      remains benign. In the absence of pancreatic cyst, mass, or localized ductal
      abnormality, total pancreatectomy is the only treatment that can completely
      remove the risk of malignant degeneration of apparently benign, mucus-secreting
      pancreatic ductal enlargement. Disability after total pancreatectomy is severe,
      but the risk of metastasis from mucinous ductal ectasia is low without pancreatic
      cyst or mass. Therefore, regular observation of mucus-secreting ductal
      enlargement with computerized tomography and pancreatography are appropriate,
      especially in older patients. Endoscopic sphincterotomy may relieve symptoms and
      allow access for ampullary biopsy and brushings.

PMID- 8995959
TI  - Regression of an aggressive abdominal desmoid tumor in a patient with familial
      adenomatous polyposis by hyperthermoradiotherapy.
AB  - A case of huge desmoid tumor successfully treated by hyperthermoradiotherapy is
      described. A 23-year-old man with familial adenomatous polyposis was operated
      upon for a desmoid tumor in the mesenterium involving the right kidney and small
      intestine in 1988. In 1990, the tumor recurred and could not be resected because
      of the involvement of the vena cava. The tumor grew larger and larger, and
      occupied two-thirds of the right lower quadrant. Several therapies using
      sulindac, tamoxifen, prednisolone, indomethacin, luteinizing hormone-releasing
      hormone analogue, and ascorbate were all ineffective. Finally, the combination of
      radiation and hyperthermia was used over a 6-month period. At the end of the
      hyperthermoradiotherapy, the tumor in the abdominal wall was markedly reduced in
      size, and the protruded abdominal wall became flat. To our best knowledge, this
      is the first report of the successful treatment of a huge desmoid tumor by
      hyperthermoradiotherapy.

PMID- 8995960
TI  - Colonic xanthelasma due to glyceride accumulation associated with an adenoma.
AB  - The case is reported of a 66-year-old woman who presented with endoscopic and
      histological features of multiple lipid deposits in the mucosa of the sigmoid
      colon associated with an adenoma. Associated clinical features were abdominal
      pain and diarrhea. Colectomy led to the complete resolution of symptoms.
      Biochemical analysis disclosed the presence of glycerides in the mucosa. The
      pathogenesis of lipid deposits and the possible link with the formation of an
      adenoma is discussed.

PMID- 8995961
TI  - Inflammatory fibroid polyp of the jejunum causing intussusception.
AB  - Inflammatory fibroid polyp of jejunum is a very rare nonneoplastic lesion of
      gastrointestinal tract. We reported a 66-year-old male who presented with
      abdominal fullness, colicky pain, and vomiting for 4 days. Plain abdomen showed
      intestinal obstruction with dilated small bowel loops. The exploratory laparotomy
      was performed under the clinical impression of intussusception caused by small
      bowel tumor. The diagnosis of an inflammatory fibroid polyp causing jejunojejunal
      intussusception was confirmed after surgery.

PMID- 8995962
TI  - Assessment of esophageal leak with oral fluorescein.
AB  - Esophageal perforation may occur spontaneously or as a complication of esophageal
      operations. Treatment often mandates emergency operative intervention to close
      the leak or to provide adequate drainage. Recurrent or persistent leak can lead
      to prolonged drainage before final healing. We describe herein a minimally
      invasive and inexpensive technique using fluorescein dye that can confirm the
      persistence of esophageal leak drained by tube thoracostomy without requiring
      expensive and potentially morbid invasive or radiological techniques. Application
      of this technique assists in diagnosis when previously described minimally
      invasive techniques are impractical or yield inconclusive results.

PMID- 8995964
TI  - Trimethoprim-sulfamethoxazole-induced vanishing bile duct syndrome.

PMID- 8995963
TI  - Enalapril-associated acute pancreatitis: recurrence after rechallenge.
AB  - Three patients with acute pancreatitis diagnosed while they were taking enalapril
      are described. In two of these patients, enalapril was the only drug taken
      immediately before the symptoms began, and other etiologies were accurately
      excluded. In the third patient, the relationship between enalapril and acute
      pancreatitis was shown by a rechallenge with the drug that resulted in severe
      acute pancreatitis. This report is a definite demonstration of the relationship
      between enalapril and acute pancreatitis. We suggest stopping treatment with
      enalapril in patients suspected of having acute pancreatitis. We also recommend
      not rechallenging patients with the drug because of the risk of inducing severe
      acute pancreatitis.

PMID- 8995965
TI  - Thalidomide for treatment of oral aphthous ulcers in patients with human
      immunodeficiency virus: case report and review.

PMID- 8995966
TI  - Could a fibroid polyp be a manifestation of enteropathy induced by nonsteroidal
      anti-inflammatory drugs?

PMID- 8995967
TI  - Tuberculosis of the pancreas: a clinical rarity.

PMID- 8995968
TI  - "Blister pack"-induced gastrointestinal hemorrhage.

PMID- 8995970
TI  - Avoiding GI surgery in the elderly: a misguided paterdistic assumption?

PMID- 8995969
TI  - Focal myositis of esophagus: a distinct inflammatory pseudotumor mimicking
      esophageal malignancy.

PMID- 8995971
TI  - Omeprazole and Barrett's regression: is asymptomatic good enough?

PMID- 8995972
TI  - Heartburn: could the heart be really burning?

PMID- 8995973
TI  - Antibiotic prophylaxis for spontaneous bacterial peritonitis.

PMID- 8995974
TI  - Accurate measurement of gastric acidity.

PMID- 8995975
TI  - Radical surgery is justified for locally advanced gallbladder carcinoma if
      complete resection is feasible.

PMID- 8995976
TI  - Re: Pulliman and Schuster: congenital markers for chronic intestinal
      pseudoobstruction.

PMID- 8995977
TI  - Duodenal obstruction caused by gallstone impaction into an intraluminal duodenal
      diverticulum.

PMID- 8995978
TI  - Naloxone for intractable pruritus?

PMID- 8995979
TI  - Strength and character.

PMID- 8995981
TI  - Just say NO.

PMID- 8995980
TI  - Cardiac troponin. See ya later, CK!

PMID- 8995982
TI  - Pulmonary function tests and idiopathic pulmonary fibrosis. Simple may be better.

PMID- 8995983
TI  - Vagotonia and bronchial asthma.

PMID- 8995984
TI  - Postoperative lung cancer surveillance. Who, what, when, and why?

PMID- 8995985
TI  - Monitoring tissue oxygenation. The search for the grail.

PMID- 8995986
TI  - Cardiac troponin I does not increase after cardioversion.
AB  - BACKGROUND: Serum total creatine kinase (total CK) level increases in the
      patients following electrical cardioversion. The same has been observed with CK
      MB, an isoenzyme of the total CK with some cardiospecificity. Cardiac troponin I
      (cTnI), a new specific cardiac biological marker, is highly effective to
      discriminate myocardial and muscular injuries after noncardiac surgery. METHODS:
      To assess cardiac damage after cardioversion, we measured serum cTnI, myoglobin,
      total CK, CK-MB mass, 1, 2, 3, 4, 8, 12, and 24 h after elective cardioversion of
      supraventricular tachycardia in 28 patients (eight women, 20 men; mean age, 64 +/
      10 years). Cumulative energy was below 370 J in 17 patients, between 370 and 900
      J in eight patients, and 1,020 J in three patients. Serum cTnI was measured using
      a sandwich immunoenzymologic assay. The detection limit of the assay was 0.35
      microgram/L and normal values range from 0.35 to 1.3 micrograms/L. RESULTS: In
      all but three patients, cTnI remained below 0.35 microgram/L. In these three
      patients, cTnI ranged between 0.35 and 0.9 microgram/L. There was no correlation
      between cTnI and the number or the energy of cardioversion. Myoglobin and total
      CK increased to abnormal concentrations in 11 patients (myoglobin, 630 +/- 190
      micrograms/L, and total CK, 2,584 +/- 780 U/L) and reached myocardial infarction
      like values in five patients. Modest increases of CK-MB were then also observed.
      A strong correlation was observed between the total energy of direct current
      cardioversion and the increase of either myoglobin (r = 0.87; p < 001) or total
      CK (r = 0.81; p < 001). CONCLUSION: Cardioversion in a clinical setting does not
      induce elevation of cTnI. Increase in total CK, CK-MB, and myoglobin may be due
      solely to muscular lesions and is closely related to the cumulative energy
      delivered.

PMID- 8995988
TI  - Cardiorespiratory response to exercise after venous switch operation for
      transposition of the great arteries.
AB  - STUDY OBJECTIVES: This study reports on the cardiorespiratory response to graded
      exercise in patients after venous switch operation for transposition of the great
      arteries. DESIGN: Several small studies have documented a diminished exercise
      tolerance after Mustard repair for transposition of the great arteries, little
      information exists, however, about long-term cardiorespiratory exercise
      performance in patients who have had the Senning procedure. PATIENTS: This
      prospective study reports on the serial long-term (mean, 11 +/- 2.8 years)
      cardiopulmonary exercise performance of 43 patients (age, 12 +/- 3.1 years) who
      underwent a Senning procedure, with no significant postoperative abnormalities.
      Forty-three matched healthy children were also studied as a control group.
      MEASUREMENTS AND RESULTS: All underwent exercise testing (Bruce protocol) with
      metabolic gas exchange to determine parameters at 3 min, anaerobic threshold,
      similar heart rate (150 beats/min), and peak exercise. Time of exercise was 10.5
      +/- 1.9 min in patients and 13.4 +/- 2 min in control subjects (p = 0.0001).
      Overall, patients reached 73% of peak oxygen uptake achieved by control subjects
      (32.6 +/- 5.6 vs 44.7 +/- 6 mL/kg/min). Chronotropic response (188 +/- 15.7 vs
      166.5 +/- 19.6 beats/min [p = 0.0001]) and oxygen pulse (7.4 +/- 2.9 vs 10.7 +/-
      4.2 mL/beat [p = 0.0002]) were lower in patients at peak exercise. Patients had a
      greater respiratory response to exercise: both respiratory rate and ventilatory
      equivalent for carbon dioxide were significantly higher at all stages of
      exercise. Exercise capacity assessed by peak oxygen uptake was correlated with
      time elapsed since surgical repair (r = 0.48; p = 0.001). CONCLUSIONS: It is
      concluded that even in asymptomatic patients, exercise endurance and respiratory
      response are generally altered as much as 11 +/- 2.8 years after venous switch
      operation, although early surgical repair is predictive of a better long-term
      functional result.

PMID- 8995989
TI  - Acute effects of intravenous cocaine on pulmonary artery pressure and cardiac
      index in habitual crack smokers.
AB  - BACKGROUND: Some habitual crack cocaine smokers who deny IV drug abuse show
      decreased pulmonary transfer of carbon monoxide (DCO). We speculated that
      repeated elevations in pulmonary artery pressure (PAP) might cause pulmonary
      capillary damage and result in a lowered DCO, or that the reduction could be due
      to anoxic lung injury secondary to repeated episodes of cocaine-induced pulmonary
      vascular constriction. STUDY OBJECTIVE: Compare the acute effects of i.v. cocaine
      HCl and placebo on PAP, cardiac stroke volume, and cardiac output estimated
      indirectly by continuous Doppler echocardiography. DESIGN: A single-blind
      crossover study in which placebo always preceded the active drug. SUBJECTS: Ten
      current crack-smoking subjects, 32 to 47 years of age, with a history of limited
      previous i.v. cocaine use. METHODS: PAP, cardiac stroke volume, heart rate, and
      BP were measured continuously after injection of placebo followed by cocaine HCl
      (0.5 mg/kg). RESULTS: i.v. cocaine resulted in no significant change in PAP (
      0.14 +/- 3.3[SD] mm Hg, 95% confidence interval [CI] for difference -2.48,
      +2.21). Stroke volume index showed no significant change after cocaine (-0.1 +/-
      2.0 mL; 95% CI, -1.5, +1.3). Heart rate showed a significant increase (10.0 +/-
      7.2 min-1; p = 0.0017, 95% CI, +4.9, +15.1). Cardiac index showed a significant
      increase (0.48 +/- 0.32 L/min; p = 0.0012, 95% CI, +0.25, +0.71). Pulmonary
      vascular resistance showed no significant change (-44 +/- 101 dyne.s.cm-5/m2, 95%
      CI, -116, +29). CONCLUSIONS: i.v. cocaine HCl does not cause short-term increases
      in PAP or stroke volume index, but causes an increase in cardiac index due to its
      chronotropic effect.

PMID- 8995987
TI  - Plasma beta-endorphin response to exercise in patients with congestive heart
      failure.
AB  - OBJECTIVE: To determine whether the net release of beta-endorphin during
      exercise, similar to that of norepinephrine, is related to functional disability
      in patients with congestive heart failure. BACKGROUND: Plasma beta-endorphin and
      norepinephrine levels are elevated at rest in patients with heart failure,
      reflecting a functional disability. The net release of beta-endorphin during
      exercise in patients with heart failure is unknown. METHODS: We measured plasma
      beta-endorphin and norepinephrine levels (respectively: radioimmune and
      radioenzymatic assay) at rest and during graded exercise testing in 28 patients
      with congestive heart failure (Weber's class A, 10; B, 9; and C, 9) and in 9
      normal subjects. RESULTS: At rest, plasma beta-endorphin levels were higher in
      patients in classes B and C than in normal subjects (p < 0.05 and < 0.01,
      respectively). At peak exercise, patients in different functional classes and
      normal subjects reached similar beta-endorphin levels. However, the net release
      of beta-endorphin during exercise was lower in patients in classes B and C than
      in those in class A and normal subjects (p < 0.01 for both). At rest, plasma
      norepinephrine levels were significantly higher in patients than in normal
      subjects (p < 0.01). At peak exercise, norepinephrine levels were significantly
      lower in class C patients than in normal subjects (p < 0.05), and tended to be
      lower in patients in classes A and B (p = NS). The net release of norepinephrine
      during exercise was lower in patients than in normal subjects (p < 0.01). In
      patients, releases of both beta-endorphin and norepinephrine during exercise were
      related to peak oxygen consumption and duration of exercise, but not to resting
      left ventricular ejection fraction. CONCLUSIONS: In patients with congestive
      heart failure, the net release of plasma beta-endorphin during exercise is
      decreased, like norepinephrine, and reflects a functional disability.

PMID- 8995990
TI  - Clinical evaluation of pulmonary hypertension in systemic sclerosis and related
      disorders. A Doppler echocardiographic study of 135 Japanese patients.
AB  - BACKGROUND: Previous studies on pulmonary hypertension (PH) in systemic sclerosis
      and related disorders used differing patient populations, and defined PH
      according to different criteria. We have attempted to determine the prevalence
      and cause of PH in these disorders using a mainly noninvasive cardiopulmonary
      evaluation. PATIENTS AND METHODS: One-hundred thirty-five Japanese patients with
      systemic sclerosis and related disorders were divided into proximal and distal
      scleroderma groups, with or without overlapping features of systemic lupus
      erythematosus (SLE) and polymyositis. They underwent multiple cardiopulmonary
      tests, including chest radiography, pulmonary function tests, and
      echocardiography to screen for pulmonary fibrosis and PH. RESULTS: The pulmonary
      artery systolic pressure was estimated by Doppler echocardiography in 80 patients
      (59%). PH (systolic pressure > or = 40 mm Hg) was diagnosed in 28 patients by the
      Doppler method and in two patients by right heart catheterization (mean pressure
      > or = 20 mm Hg). Doppler-estimated pulmonary artery pressures were significantly
      higher in patients with proximal scleroderma (p < 0.05), and in those with an
      SLE/polymyositis overlap (p < 0.01). The FVC was significantly reduced in the
      proximal scleroderma group (p < 0.0005), but not in the overlap group. PH was
      attributable to pulmonary fibrosis in nine patients who had proximal scleroderma
      without overlap. Pulmonary arteriopathy was the probable cause of PH in seven
      patients with overlap and in four patients who had proximal scleroderma without
      overlap. CONCLUSIONS: These findings suggest that proximal scleroderma
      predisposes patients to PH mainly because of pulmonary fibrosis, but occasionally
      because of pulmonary arteriopathy. An overlap of SLE/polymyositis predisposes
      patients to PH due to the occurrence of arteriopathy.

PMID- 8995991
TI  - Exhaled nitric oxide during exercise in primary pulmonary hypertension and
      pulmonary fibrosis.
AB  - STUDY OBJECTIVES: Nitric oxide (NO), a potent vasodilator, is present in the
      exhaled air of humans. We wished to quantify NO production in patients with
      abnormalities of the pulmonary circulation. PARTICIPANTS: Nine patients with
      primary pulmonary hypertension (PPH), six with pulmonary fibrosis (PF), and 20
      normal volunteers were studied. INTERVENTIONS: All subjects were studied at rest
      and during continuous incremental (ramp) cycle ergometry exercise. All patients
      with PPH and nine matched normal volunteers also performed constant exercise at
      equal absolute work rates. MEASUREMENTS AND RESULTS: The concentration of NO was
      measured continuously in mixed expired air, and the rate of NO production (VNO)
      calculated. Peak exercise capacity was markedly impaired in both patient groups.
      VNO was similar at rest in the PPH patients (142 +/- 84 nL/min) and the normal
      subjects (117 +/- 45 nL/min), but lower in the PF patients (66 +/- 13 nL/min; p <
      0.05; analysis of variance with Bonferonni correction). While VNO in normal
      subjects more than doubled by peak exercise to 268 +/- 85 nL/min, there was no
      significant rise with exercise in either patient group (PPH, 155 +/- 81 nL/min;
      PF, 91 +/- 67 nL/min). Constant work rate exercise induced a significant rise in
      VNO in the normal subjects (rest, 101 +/- 68 nL/min; exercise, 147 +/- 87 nL/min;
      p < 0.001) but no significant change in the PPH patients (rest, 127 +/- 111
      nL/min; exercise, 68 +/- 65 nL/min). CONCLUSIONS: We conclude that the low
      resting VNO in PF may be due to loss of normal functional pulmonary capillary
      bed. The increase in VNO seen in normal subjects may be associated with
      dilatation and recruitment of the pulmonary capillary bed during exercise, and
      failure to increase VNO during exercise in disease states may reflect an
      inability to recruit the capillary bed.

PMID- 8995992
TI  - Lung function tests in patients with idiopathic pulmonary fibrosis. Are they
      helpful for predicting outcome?
AB  - STUDY OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) varies widely in its course.
      To evaluate predictive parameters at presentation to the hospital, we
      investigated 99 patients with IPF (47 women), focusing on extensive lung function
      tests. METHODS: Standard tests of lung volumes, arterial oxygen tension, and gas
      exchange at rest and during bicycle exercise were performed. Survival rates in
      relation to functional parameters were calculated using the actuarial method.
      Differences in survival proportions were summarized as hazard ratios, and
      significance levels were determined by log-rank test. RESULTS: At presentation,
      most patients showed a reduced total lung capacity (TLC) of 79.2 +/- 21.1%, an
      arterial oxygen tension (PaO2) considered pathologic in 63%, when related to age,
      a significant decrease of PaO2 with 11.8 +/- 12.1 mm Hg and an increase of the
      alveolar-arterial oxygen pressure difference with 46.4 +/- 16.4 (12.2 to 76.8) mm
      Hg during bicycle exercise. Diminished survival was associated with an age older
      than 50 years, a reduced value to more than 2 SDs below the predicted values of
      both, TLC alone, or in combination with a reduced vital capacity. Factors not
      influencing survival were gender, parameters of gas exchange at rest, and PaO2 at
      rest and during bicycle exercise. CONCLUSIONS: We conclude that standard lung
      function tests make it possible to assess the prognosis of patients with IPF,
      while extensive tests like gas exchange measurements at rest and during bicycle
      exercise do not contribute additional information to make the prognostic
      estimations more precise.

PMID- 8995993
TI  - Low pulmonary diffusing capacity in subjects with acute mountain sickness.
AB  - This study was conducted to investigate whether the changes in the pulmonary
      diffusing capacity found in individuals with acute mountain sickness (AMS)
      reflect the early stage of high-altitude pulmonary edema (HAPE). We measured the
      pulmonary diffusion capacity for carbon monoxide (DCO) by the single-breath
      method, arterialized capillary blood gas, and spirometry in a group of 32 healthy
      subjects (24 men, eight women) at an altitude of 2,260 m and after ascent to
      4,700 m. Twelve subjects (10 men, two women) had symptoms of AMS (AMS group) by
      the second day after arrival at 4,700 m, but none had clinical signs of pulmonary
      or cerebral edema. In the non-AMS group, almost all subjects exhibited an
      increase in DCO at 2,260 to 4,700 m (delta DCO, 10.7 +/- 1.25 mL/min/mm Hg),
      while the degree of increase in DCO in the AMS group (n = 12) was significantly
      lower (delta DCO, 1.26 +/- 1.74 mL/min/mm Hg) than that of the non-AMS group (p <
      0.01). In four of the 12 subjects with AMS who had a high AMS score, DCO
      decreased from 38.4 +/- 4.5 to 33.2 +/- 5.3 mL/min/mm Hg (delta DCO, -5.84 +/-
      1.1 mL/min/mm Hg). The AMS group showed significantly lower vital capacity,
      forced expiratory flow during the middle half of FVC, PaO2, and a greater
      alveolar-arterial oxygen pressure difference at 4,700 m compared with the non-AMS
      group. DCO showed a significant negative correlation with AMS score (r = -0.885)
      and a positive correlation with PaO2 (r = 0.757) at 4,700 m. These results
      suggest that the decreased pulmonary diffusing capacity in subjects with AMS
      reflects the presence of pulmonary gas exchange abnormality, which is probably
      due to subclinical interstitial edema of the lung.

PMID- 8995994
TI  - Autonomic regulation in asthmatics with gastroesophageal reflux.
AB  - STUDY OBJECTIVE: To study the role of autonomic regulation in asthmatics with
      gastroesophageal reflux (GER). DESIGN: Prospective study. SETTING: Autonomic
      function laboratory of a 908-bed university hospital. PARTICIPANTS: Fifteen
      nonsmoking asthmatics with GER (six men, nine women; average age, 36 years).
      INTERVENTIONS: Subjects were connected to an ECG monitor. BP was measured by
      sphygmomanometer at set intervals. After a resting period, each subject had heart
      rate and BP monitored during an 80 degrees passive tilt, Valsalva maneuver, quiet
      and deep breathing, handgrip, and an echo stress test of cortical arousal. Each
      autonomic function test was analyzed and defined as normal, hypervagal,
      hyperadrenergic, or mixed (a combination of hypervagal and hyperadrenergic
      responses) as compared with 23 age-matched normal control subjects from our
      laboratory (14 men, 9 women; average age, 35 years) and published normal control
      values. Each subject had an overall response score that was determined by the
      results of the tilt, Valsalva maneuver, and deep breathing maneuvers. RESULTS:
      All asthmatics with reflux had at least one autonomic function test display a
      hypervagal response. Overall response scores show that eight of 15 asthmatics
      with GER had an overall hypervagal response, and seven had a mixed response. Of
      the seven asthmatics with GER who had a mixed response score, two had a
      hypervagal predominant response. CONCLUSIONS: Asthmatics with GER have evidence
      of autonomic dysfunction. Heightened vagal tone may be partially responsible for
      the heightened airway responsiveness to esophageal acidification in asthmatics
      with reflux.

PMID- 8995995
TI  - The effect of nebulized albuterol on the activity of the renin-angiotensin system
      in asthma.
AB  - STUDY OBJECTIVE: We have previously described activation of the renin-angiotensin
      system (RAS) in acute severe asthma and have also reported activation of the RAS
      in normal subjects by single doses of nebulized beta 2-agonists. In the present
      study, we have examined the effect of single and multiple doses of nebulized
      albuterol on the activity of the RAS in mild asthma. DESIGN: Eight patients with
      mild asthma were studied. The effect of single and multiple doses of nebulized
      albuterol (5 mg) on the activity of the RAS was compared with that of placebo
      using a randomized, double-blind crossover study design. Nebulized drugs were
      administered at time 0 and 30 min. MEASUREMENTS: Plasma renin, angiotensin II
      (Ang II), and serum potassium levels were measured at baseline following a short
      rest, and thereafter at intervals up to 150 min. RESULTS: Renin levels increased
      after both the single (S) and double (D) nebulized doses of albuterol and were
      significantly greater than placebo at 30 min after S, and at 45 and 120 min after
      D. Plasma Ang II level also increased after S and D and was significantly greater
      than placebo at 30 and 45 min after S, and at 30 min and all timepoints
      thereafter following D. In addition, the effect of D was significantly greater
      than S at 45 min. CONCLUSIONS: These results confirm that there is activation of
      the RAS in asthmatic subjects by single doses of nebulized beta 2-agonists and
      that repeated dosing with nebulized albuterol has further, additive effects on
      plasma Ang II levels. It therefore seems likely that these agents are
      contributing to activation of the RAS in acute asthma, although the exact
      clinical significance of these transient changes in plasma Ang II levels in
      asthma is at present unclear.

PMID- 8995996
TI  - Specific immunoglobulins to soybean hull allergens in soybean asthma.
AB  - Soybean asthma, which occurred as an epidemic among patients in Barcelona, Spain,
      is associated with specific IgE to soybean hull allergens. The purpose of this
      study was to investigate the possible role of specific IgG, IgG subclasses, IgA,
      and IgM in the pathogenesis of soybean asthma. We studied 3 groups of subjects
      from Barcelona: group 1, 12 asthmatic epidemic patients; group 2, 23 asthmatic
      nonepidemic patients; and group 3, 32 nonallergic subjects. Specific IgE was
      determined by radioimmunoassay and specific IgG, IgG subclasses (1, 2, 3, and 4),
      IgA, and IgM by amplified enzyme-linked immunosorbent assay. Cross-inhibition
      studies were performed for specific IgE and IgG4. We partially characterized the
      soybean hull allergens that bind specific IgE, IgG, and IgG4 by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis/Western blot. Percentage of positive
      results for the assays of the 8 Igs are as follows: for group 1, 100% (IgE), 75%
      (IgG), 16.6% (IgG1), 8.3% (IgG2), 0% (IgG3), 66.6% (IgG4), 25% (IgA), and 25%
      (IgM); for group 2, 4.3% were positive for specific IgE only; and for group 3, 0%
      (IgE), 0% (IgG), 6.2% (IgG1), 9.4% (IgG2), 9.4% (IgG3), 9.4% (IgG4), 6.2% (IgA),
      and 6.2% (IgM). The correlation between the specific IgE and the other specific
      Igs was significant between IgE and IgG4 in group 1 only (r = 0.752, p < 0.01).
      Cross-inhibition studies demonstrated a higher inhibitory capacity for IgG4 than
      for IgE. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/ Western blot
      demonstrates three low molecular weight protein bands that bind specific IgE,
      IgG, and IgG4. This study suggests that specific IgG4 to soybean hull allergens
      plays a role in the pathogenesis of soybean asthma and corroborates the role of
      specific IgE in the same disease.

PMID- 8995997
TI  - Reduction of environmental tobacco smoke exposure in asthmatic children. A 2-year
      follow-up.
AB  - STUDY OBJECTIVE: To examine the long-term maintenance of a previously reported
      behavioral counseling intervention to reduce asthmatic children's exposure to
      environmental tobacco smoke (ETS). PARTICIPANTS: Families of asthmatic children
      (6 to 17 years), including at least one parent who smoked in the home, recruited
      from four pediatric allergy clinics. DESIGN: Participants were randomized to one
      of three groups: behavioral counseling to reduce ETS exposure, self-monitoring
      control, and usual medical care control. Counseling concluded at month 6, and the
      original trial ended at month 12. Two follow-up interviews occurred at months 20
      and 30. MEASUREMENTS AND RESULTS: The originally reported analysis of baseline to
      12 months was reanalyzed with a more robust restricted maximum likelihood
      procedure. The 2-year follow-up period was analyzed similarly. Significantly
      greater change occurred in the counseling group than the control groups and was
      sustained throughout the 2 years of follow-up. Further exploratory analyses
      suggested that printed counseling materials given to all participants at month 12
      (conclusion of the original study) were associated with decreased exposure in the
      control groups. CONCLUSION: Such long-term maintenance of behavior change is
      highly unusual in the general behavioral science literature, let alone for
      addictive behaviors. We conclude that ETS exposure can be reduced and that a
      clinician-delivered treatment may provide substantial benefit.

PMID- 8995998
TI  - Reducing length of stay for patients hospitalized with exacerbation of COPD by
      using a practice guideline.
AB  - Clinical practice guidelines have been promoted as an effective way of reducing
      costs while maintaining quality care. OBJECTIVE: To study a practice guideline to
      shorten length of stay for patients hospitalized with exacerbation of COPD.
      METHODS: We retrospectively studied a practice guideline to identify patients who
      were at low risk of complications from their exacerbation of COPD and hence
      potentially suitable for early hospital discharge. We then prospectively studied
      the practice guideline using an alternate month intervention and control time
      series over a period of 12 months. RESULTS: The practice guideline was
      retrospectively studied in 250 consecutive patients hospitalized with
      exacerbation of COPD. Of the 250 patients, 237 patients (94.8%) were classified
      as low risk after 72 h of hospitalization and were potentially suitable for
      discharge. In the prospective study, few patients (24 of 124 or 19%) were
      identified for implementation of the guideline. However, in those patients who
      were identified, length of stay was not statistically different. The data also
      showed that length of stay for both intervention and control groups had shortened
      over this time. CONCLUSION: Certain practice guidelines may appear efficacious in
      studies but may actually lack effectiveness when applied in clinical settings and
      may even increase costs. We demonstrated the importance of prospectively
      evaluating clinical practice guidelines before recommending them for widespread
      implementation.

PMID- 8995999
TI  - Clinical and personality profiles and survival in patients with COPD.
AB  - OBJECTIVE: To assess the relationship of personality and clinical characteristics
      with survival in patients with advanced chronic obstructive pulmonary disease
      (COPD). DESIGN: Prospective double-blind study. SETTING: Outpatient clinic of a
      teaching Veterans Affairs Hospital in central New York. PATIENT PARTICIPATION:
      Sixteen male patients (mean age, 62.2 +/- 2.5 years) with severe COPD
      INTERVENTIONS: Patients were administered Minnesota Multiphasic Personality
      Inventory (MMPI) test; their clinical features were recorded from hospital
      records at the time of admission into the study. All were followed up for 4 years
      after the initial assessment or until their death. MEASUREMENTS AND MAIN RESULTS:
      The nine survivors and seven nonsurvivors were similar in age, pulmonary function
      test (PFT) results, oxygenation, number of medications, or concomitant illnesses.
      However, the nonsurvivors had higher MMPI and clinical illness scores compared
      with the survivors (p < 0.01 and < 0.05, respectively). CONCLUSIONS: The 4-year
      mortality in male veterans with severe COPD is influenced by overall
      psychological distress and difficulty in coping with their disease, which seem to
      be important prognostic indicators irrespective of PFT results or oxygenation.

PMID- 8996000
TI  - How tumor stage affects surgeons' surveillance strategies after lung cancer
      surgery.
AB  - The factors that influence decision making among surgeons are not well
      understood. We evaluated how tumor stage in patients subjected to potentially
      curative surgery for lung cancer affects the self-reported follow-up strategies
      employed by practicing surgeons. Hypothetical patient profiles and a detailed
      questionnaire based on these profiles were mailed to the 3,700 members of the
      Society of Thoracic Surgeons. The effect of TNM stage on the surveillance
      strategies chosen by the respondents was analyzed. All of the ten most commonly
      employed surveillance modalities were ordered significantly more frequently with
      increasing TNM stage, although the differences are small. Only 23% of respondents
      modified their strategies according to the patient's TNM stage. This effect
      persisted through 5 years of follow-up. We conclude that most surgeons performing
      surveillance after potentially curative surgery for otherwise healthy patients
      with lung cancer use the same follow-up strategy irrespective of TNM stage. These
      data should help in the design of prospective trials of this topic.

PMID- 8996001
TI  - Relevance of training in transbronchial fine-needle aspiration technique.
AB  - Transbronchial fine-needle aspiration (TBFNA) is a valuable and low-risk
      procedure that provides access to mediastinal nodes. To learn if increased
      experience improved TBFNA performance, we compared overtime TBFNA diagnostic
      yields between a skilled bronchoscopist and another without experience on TBFNA
      technique. We found higher TBFNA yields in the experienced bronchoscopist (p <
      0.001); however, after some experience, the TBFNA reliability improved (p < 0.02)
      and the use of the procedure increased (p < 0.0001). Thus, to achieve acceptable
      TBFNA results, a training period is required that we estimate in about 50
      procedures.

PMID- 8996003
TI  - Morphometric evaluation of argyrophilic nucleolar organizer region is useful in
      predicting long-term survival in squamous cell carcinoma of the lung.
AB  - Nucleolar organizer regions identified by means of an argyrophilic technique
      (AgNOR) were quantified by digital image analysis in 81 patients with squamous
      cell carcinoma of the lung. Survival rate was modeled as function of AgNOR
      expression by Cox regression models controlled for staging, histologic grade,
      age, and sex. Our results indicate that AgNOR expression has a significant
      prognostic role. Tumors at lower stages have a lower expression of AgNOR than
      those with more advanced disease. Tumors with high histopathologic grade have a
      higher expression of AgNOR. Patients with low AgNOR expression presented a higher
      survival rate than those with higher amounts of AgNOR. The foregoing results
      strongly encourage the development of prospective trials to assess the real role
      of AgNOR in determining prognosis in squamous cell carcinoma of the lung.

PMID- 8996002
TI  - The role of cytologic evaluation of pleural fluid in the diagnosis of malignant
      mesothelioma.
AB  - STUDY OBJECTIVE: Treatment of malignant mesothelioma (MM) at an early stage
      results in increased survival. Cytologic examination of pleural effusions is one
      of the first diagnostic techniques attempted in these patients. The objective of
      this study was to define the role of cytologic examination of pleural fluid in
      facilitating early diagnosis. DESIGN: The medical records and cytologic slides of
      patients with pleural MM were reviewed. SETTING: Medical records were reviewed
      from two institutions: a large general hospital and a cancer hospital. PATIENTS:
      Twenty-nine patients ranging in age from 32 to 81 years (mean, 59 years) met the
      study criteria. INTERVENTIONS: All patients had at least one cytologic pleural
      fluid examination. MEASUREMENTS AND RESULTS: The median time from initial
      symptoms to the diagnosis of MM was 8 weeks for all patients. For patients with a
      positive or suspicious cytologic result, the median was 4 weeks, and in those
      with a negative cytologic result, it was 12 weeks. The overall sensitivity of
      cytologic examination for the diagnosis of MM was 32%. Cytogenetic analysis of
      pleural fluid had a sensitivity of 56%, and was positive in 1 case in which
      results of cytologic examination were negative. Patients in whom the time from
      presentation to diagnosis was greater than 1 year all had negative cytologic
      results followed by long periods without further workup, despite a history of
      exposure to asbestos. CONCLUSIONS: A positive or suspicious cytologic result was
      associated with a decreased median time to diagnosis. Unfortunately, the
      sensitivity of cytologic examination for a diagnosis of MM was only 32%. Until
      better diagnostic techniques are developed, we recommend immediate pleural biopsy
      in patients in whom MM is suspected and cytologic evaluation of pleural fluid
      gives negative results.

PMID- 8996004
TI  - Obstructive atelectasis in patients with small cell lung cancer. Incidence and
      response to treatment.
AB  - STUDY OBJECTIVES: Define the incidence of obstructive atelectasis in patients
      presenting with small cell lung cancer and their response to treatment. DESIGN:
      Retrospective review of clinical records and radiographic studies. SETTING:
      Single federal government institution-the National Cancer Institute-Naval Medical
      Oncology Branch. PATIENTS: One hundred seventy-two consecutive patients treated
      between 1983 and 1993. INTERVENTIONS: Patients presenting with obstructive
      atelectasis were identified. The incidence of dyspnea, cough, and sputum
      production before starting treatment and 1, 3, and 6 months later was determined.
      Fiberoptic bronchoscopy and chest radiographs performed before starting treatment
      were compared with those obtained later in the patients' clinical course.
      MEASUREMENTS AND RESULTS: Thirty-seven of 172 (22%) patients had obstructive
      atelectasis. Initial symptoms included cough in 25 (68%), dyspnea in 24 (65%),
      and productive cough in 10 (27%). The patients' symptoms of cough, dyspnea, and
      sputum production decreased to one third of the initial prevalence 1 month after
      the start of treatment. Fiberoptic bronchoscopy and chest radiographs performed 3
      months after starting treatment demonstrated bronchial patency in 90%.
      CONCLUSIONS: Obstructive atelectasis occurs in approximately one fifth of
      patients presenting with small cell lung cancer. Chemotherapy and chemotherapy
      plus chest radiotherapy lead to symptomatic, bronchoscopic, and radiographic
      resolution in similar proportions of patients with obstructive atelectasis.

PMID- 8996005
TI  - Nonspecific airway hyperresponsiveness in HIV disease. Pulmonary Complications of
      HIV Infection Study Group.
AB  - OBJECTIVES: HIV disease is frequently complicated by episodic acute bronchitis,
      suggesting the presence of chronic bronchial inflammation. To further examine
      this concept, we investigated the possible association of nonspecific airway
      hyperresponsiveness (AHR) and HIV disease. DESIGN: Methacholine inhalation
      challenge studies were performed on 66 HIV-seropositive and 8 HIV-seronegative
      members of the Pulmonary Complications of HIV Infection Study Cohort. AHR was
      defined as 20% or more decline in FEV1 from the postdiluent value after
      inhalation of 125 or less cumulative breath units. The prevalence of AHR in HIV
      seropositive cohort members was compared with that in matched control subjects
      who had undergone methacholine challenge testing for two unrelated studies.
      Demographic, behavioral, and clinical features in HIV cohort members with and
      without AHR were contrasted. The relationship between AHR and the occurrence of
      episodic airway disease or symptoms suggestive of airway disease was examined.
      RESULTS: AHR was not more prevalent in HIV-seropositive cohort members than
      control subjects (19.3% vs 12.9%; p > 0.1). Within the cohort, AHR was detected
      more frequently in members with than without a history of asthma (60% vs 16%; p <
      0.05). A greater proportion with than without AHR had 1 or more episode of
      pneumonia within 2 years (46% vs 9%; p < 0.01), 1 or more asthma episode during
      the study period (39% vs 1.9%; p < 0.001), or wheeze noted during clinic visits
      (62% vs 17%; p < 0.01). The proportion that experienced acute bronchitis did not
      differ in the two groups. CONCLUSIONS: This study suggest that HIV-infected
      persons do not have increased prevalence of nonspecific AHR. In HIV disease, AHR
      is associated asthma, but not episodic acute bronchitis. Thus, the possibility
      that airway injury without demonstrable AHR might complicate HIV disease remains.

PMID- 8996006
TI  - Cytomegalovirus as a primary pulmonary pathogen in AIDS.
AB  - In patients with AIDS, isolation of cytomegalovirus (CMV) from respiratory
      secretions is common. It is often found with other pathogens, which has led to
      debate regarding its role as a primary pulmonary pathogen. A retrospective
      investigation of patients with AIDS and CMV as a sole pulmonary isolate was
      performed in an attempt to describe their clinical presentation and course. All
      patients admitted to the hospital with pneumonia and with BAL or transbronchial
      biopsy (TBB) specimen positive for CMV between 1991 and 1994 were identified
      through a review of inpatient records. Inclusion criteria included positive CMV
      cultures from BAL, cytomegalic inclusion bodies from BAL or TBB, and thorough
      documentation of the absence of other pulmonary pathogens. Nine patients met the
      inclusion criteria for CMV pneumonitis. Seven were male and two were female, ages
      26 to 44 years, and all had a history of opportunistic infections. Typical
      clinical presentation was characterized by increased respiratory rate, hypoxemia,
      and diffuse interstitial infiltrates. The mean CD4 count was 29.6 (+/- 22) cells
      per cubic millimeter, mean lactate dehydrogenase level was 414 (+/- 301) IU/L,
      and in seven patients in whom CMV antigen was measured it was greater than 50
      positive cells per 200,000 WBCs. Three untreated patients died of respiratory
      failure and three had autopsy confirmation of CMV pneumonia. Five patients were
      treated with anti-CMV therapy for at least 2 weeks, and all demonstrated
      improvement in symptoms, oxygen saturation, and chest radiograph. At 3 months
      follow-up, all five patients were asymptomatic with no pulmonary symptoms. At 6
      months follow-up, three of the five patients remained asymptomatic; the other two
      died of other opportunistic infections. In at least these nine patients, CMV
      represented a primary pulmonary pathogen. Patients who were treated responded
      quickly and were able to be discharged home from the hospital with marked
      improvement in their symptoms. We recommend that clinicians consider this
      diagnosis in the proper setting and consider treatment with anti-CMV therapy.

PMID- 8996007
TI  - Bronchoscopic evaluation of pulmonary infiltrates following bone marrow
      transplantation.
AB  - STUDY OBJECTIVE: To determine the impact of fiberoptic bronchoscopy (FOB),
      including quantitative bacterial cultures obtained by BAL and protected specimen
      brushing on therapeutic decisions and outcome in bone marrow transplant (BMT)
      patients. DESIGN: Retrospective review of all BMT patients undergoing FOB during
      a 4-year period. SETTING: A tertiary care university hospital. RESULTS: Three
      hundred five patients underwent BMT; 71 (23%) had FOB to assess pulmonary
      infiltrates. Allogeneic BMT recipients underwent FOB 3.37 times more often than
      autologous recipients (p < 0.001). Pathogens were identified in 31 (46%) patients
      undergoing FOB; bacteria were most commonly isolated although 86% of patients had
      received broad-spectrum empiric antibiotics. Therapy was changed in 20 (65%)
      patients when a microorganism was identified and in 9 (22%) with nondiagnostic
      results (p = 0.0026), but isolation of a presumed pathogen had no apparent effect
      on survival. There were 19 (27%) FOB complications, including bleeding in 8 (11%)
      patients and death in 2 (3%). Major complications were associated with prolonged
      prothrombin time (p = 0.006) and were more common (36% vs 14%; p < 0.05) in
      patients who had protected specimen brushing vs BAL alone. Mortality at 40 months
      in BMT patients not requiring FOB was 33% compared with 61% mortality in those
      undergoing FOB (p < 0.001); mortality was 96% in patients with respiratory
      failure requiring mechanical ventilation. CONCLUSION: FOB is diagnostically
      useful in the evaluation of some BMT patients with pulmonary complications and
      often influences therapy, although no impact on survival was clearly
      demonstrated. FOB should be performed only after benefits of the procedure are
      weighed carefully against its increased risk in this select population.

PMID- 8996008
TI  - The significance of Mycobacterium avium complex cultivation in the sputum of
      patients with pulmonary tuberculosis.
AB  - Mycobacterium avium-intracellulare complex (MAC) is a ubiquitous environmental
      microorganism whose pathogenicity ranges from innocuous colonization to disease,
      in immunocompetent as well as immunocompromised individuals. We sought to
      determine the clinical significance of MAC in sputum cultures of patients with
      pulmonary tuberculosis (TB). A retrospective analysis between January 1994 and
      March 1995 at Bellevue Hospital Center revealed both Mycobacterium tuberculosis
      and MAC in 35 patients (11% of all patients with TB). Of 27 patients reviewed,
      52% were HIV-1 infected (median CD4 + 25 cells per microliter). Radiographic
      manifestations in patients with TB and MAC were similar to those seen in patients
      with TB alone. Both mycobacteria were cultured primarily from respiratory
      sources. M tuberculosis was usually cultured first or concurrent with MAC, and in
      nearly all cases, both species were recovered within 2 months of each other. Most
      patients improved clinically, bacteriologically, and radiographically with
      standard antituberculous therapy, except those with advanced AIDS, multidrug
      resistant TB (MDR-TB), or disseminated MAC. We conclude that recovery of MAC in
      sputum is common in patients with pulmonary TB, regardless of HIV-1 infection,
      MDR-TB, or other clinical, bacteriologic, or radiographic attributes. MAC
      cultivation in most of these patients likely represents transient colonization,
      and in most cases is not clinically significant.

PMID- 8996010
TI  - Contribution of craniofacial risk factors in increasing apneic activity among
      obese and nonobese habitual snorers.
AB  - STUDY OBJECTIVE: To determine the role of craniofacial risk factors in increasing
      apneic activity between nonobese and obese habitual snorers. DESIGN: Cross
      sectional. SETTING: Care-seeking volunteers identified through advertisements,
      and referral-based volunteers from two sleep centers serving the greater
      Cleveland area. PATIENTS: The study included 142 habitual snorers (mean +/- SD,
      45.5 +/- 10.6 years, 68% men; 20% African-Americans) MEASUREMENTS AND RESULTS:
      Apneic activity was determined using unattended home sleep monitoring to assess
      the respiratory disturbance index (RDI). Independent variables included body mass
      index, cranial index, facial index, and 13 anatomic variables (lateral and
      frontal cephalometric radiographs were used to characterize craniofacial hard and
      soft tissues). A linear regression model explained approximately 54% and 53% of
      the variation in RDI (log transformed) scores for the nonobese and obese groups,
      respectively. The largest predictor of RDI in the nonobese group was tongue
      length, followed by alignment of the middle cranial fossa, and age. In the obese
      group, the largest predictor of RDI was hyoid to mandibular plane, followed by
      tongue length. CONCLUSIONS: Measurements of soft tissues of the oropharynx
      (especially the tongue) are more closely associated with increased apneic
      activity. In addition, the hard tissue anatomic limits of the oropharynx may
      place nonobese individuals in the at-risk group. Therefore, anatomic
      relationships that are temporally stable may be useful to predict apneic activity
      in later years.

PMID- 8996009
TI  - Drug-resistant Mycobacterium tuberculosis and atypical mycobacteria isolated from
      patients with suspected pulmonary tuberculosis in Honduras.
AB  - BACKGROUND: Tuberculosis is a major health problem in Central America. In
      Honduras, with an incidence rate of 81/100,000, it is an increasingly common
      cause of morbidity and hospitalization. This study was conducted to examine drug
      resistant tuberculosis and prevalence of infection with atypical mycobacteria in
      Honduran patients with suspected pulmonary tuberculosis. METHODS: Pulmonary
      specimens from 235 Honduran patients with suspected tuberculosis were examined by
      acid-fast smears and culture. The 95 mycobacterial strains isolated were
      identified to species level and drug susceptibility tests were carried out.
      Resistant Mycobacterium tuberculosis strains were tested for susceptibility to
      six additional drugs. Their possible relationship was studied by DNA restriction
      fragment length polymorphism. RESULTS: Drug-resistant strains were found in 13 of
      85 culture-verified tuberculosis patients, including 10 with isolates of
      multidrug-resistant bacteria. Seven of the patients with multidrug-resistant
      tuberculosis had smear-positive disease. Nine of them had a history of specific
      therapy. Two patients with drug-resistant disease were shown to be infected by
      identical strains. Only one of 11 HIV-positive patients had drug-resistant
      tuberculosis. Most resistant strains were susceptible to ciprofloxacin, amikacin,
      kanamycin, and pyrazinamide. Atypical mycobacteria were isolated from 10 patients
      with suspected tuberculosis. Seven of them were receiving antituberculosis
      chemotherapy and five had smear-positive samples. CONCLUSIONS: These results
      illustrate the importance of mycobacterial culture and subsequent species
      identification and in vitro susceptibility testing for identification of patients
      with drug-susceptible or drug-resistant tuberculosis and those infected or
      colonized with other mycobacteria.

PMID- 8996011
TI  - Reversal of central sleep apnea with oxygen.
AB  - OBJECTIVE: To examine the effect of oxygen on apneas and sleep quality in
      patients with frequent central apneas during sleep. DESIGN/SUBJECTS: Prospective
      intervention study of 20 consecutive patients with predominant central apnea
      identified from 570 patients referred for suspected sleep apnea syndrome. Sixteen
      patients had congestive heart failure and seven of them had a previous stroke.
      Three of the remaining four patients without heart failure had experienced a
      previous stroke, and one was being treated with morphine. SETTING: The Department
      of Pulmonary Medicine at Umea (Sweden) University Hospital. INTERVENTIONS: The
      patients were investigated for one night receiving nasal oxygen and one night
      without it. MEASUREMENTS: Overnight polysomnography with transcutaneous PCO2 and
      arterial blood gases. RESULTS: Central apneas occurred during Cheyne-Stokes
      respiration in 18 of 20 patients and two patients had idiopathic central apneas.
      Without oxygen, the median number of all central apneas and hypopneas was 33.5
      (range, 8.0 to 52.0) per hour of sleep. These episodes decreased to 5.0 (range,
      0.0 to 31.0)(p < 0.01) during oxygen therapy. In 17 of 20 patients, the frequency
      of central apneas was reduced by more than 50%. Central apneas were reduced by
      oxygen irrespective of the presence or absence of heart failure or Cheyne-Stokes
      respiration. The arousal frequency was reduced during oxygen treatment. Daytime
      sleepiness, difficulty falling asleep, snoring, and self-scored awakenings were
      reduced in seven patients who were given nocturnal oxygen at home. Obstructive
      and mixed apneas were unaffected by oxygen. CONCLUSIONS: Oxygen effectively
      reduces central sleep apnea in eucapnic patients.

PMID- 8996012
TI  - High prevalence of allergic sensitization in children with habitual snoring and
      obstructive sleep apnea.
AB  - STUDY OBJECTIVE: To determine whether allergic sensitization occurs frequently in
      children with habitual snoring and whether allergy predicts the occurrence of
      obstructive sleep apnea syndrome (OSAS) in snoring children. DESIGN: Prospective
      study of 39 children with habitual snoring who were referred for polysomnography.
      SETTING: Pediatric pulmonary sleep disorders clinic in a tertiary referral
      center. MEASUREMENTS: Subjects underwent a complete history and physical
      examination. To assess for the presence of allergic sensitization, a multiantigen
      radioallergosorbent test (RAST) was performed on serum samples. Subjects then
      underwent nocturnal polysomnography to determine the presence and severity of
      OSAS. RESULTS: Fourteen subjects (36%) demonstrated sensitivity to allergens;
      this is higher than expected for the general pediatric population. The frequency
      of OSAS was increased in subjects with positive RAST results compared to those
      with negative RAST results (57% vs 40%; chi 2 = 9.11; p < 0.01). CONCLUSION:
      Allergy is frequently present in pediatric patients with habitual snoring.
      Furthermore, the presence of allergy is associated with an increased risk of OSAS
      in this population.

PMID- 8996013
TI  - The DCO2 measured by gastric tonometry predicts survival in children receiving
      extracorporeal life support. Comparison with other hemodynamic and biochemical
      information. Royal Children's Hospital ECMO Nursing Team.
AB  - STUDY OBJECTIVE: To assess the role of gastric tonometry in monitoring children
      receiving extracorporeal life support (ECLS) and to determine if DCO2 or pHi in
      the weaning phase of ECLS predicts survival. DESIGN: A prospective study of
      consecutive patients treated with ECLS. SETTING: A tertiary pediatric ICU that is
      the ECLS referral center for Australia. PATIENTS: Twenty consecutive children
      receiving ECLS for cardiovascular or respiratory failure. INTERVENTIONS: All
      children were monitored throughout their ECLS course using a tonometer inserted
      into the stomach via the orogastric route. The PCO2 in the tonometer balloon was
      measured every 4 to 6 h and the pHi was calculated using the Henderson
      Hasselbalch equation. The DCO2, which is the difference between PCO2 in tonometer
      saline solution and arterial blood, was calculated. We compared the ability of
      pHi, DCO2, heart rate, mean arterial pressure, arterial pH, base deficit, and
      blood lactate to predict death or survival during the weaning phase. Measurements
      were taken on the lowest level of support, which for veno-arterial extracorporeal
      membrane oxygenation and ventricular assist device was defined as the lowest ECLS
      pump flows, and on veno-venous extracorporeal membrane oxygenation was defined as
      the time of lowest ECLS gas flow. Predictive power was assessed using the
      receivor operating characteristic (ROC) analysis on the data collected at these
      times. RESULTS: In the weaning phase of ECLS, the pHi was significantly lower in
      children who died (pHi = 7.21; 95% confidence intervals, 7.14 to 7.28) than in
      those who survived (pHi = 7.38; 95% confidence intervals, 7.28 to 7.47). The DCO2
      was significantly higher in children who died (23.6 mm Hg; 95% confidence
      intervals, 14.3 to 33.1) compared with survivors (4.7 mm Hg; 95% confidence
      intervals, -0.78 to 10.1). The area under the ROC curve was 0.95 for DCO2 (and
      0.88 for pHi). pHi and DCO2 predicted survival better than base deficit (area
      under ROC curve, 0.82), blood lactate level (0.29), arterial pH (0.65), heart
      rate (0.62), and mean arterial pressure (0.74). CONCLUSIONS: DCO2 is a clinically
      meaningful measurement in children receiving ECLS. A high DCO2 was a good
      predictor of death in this series. Gastric tonometry may provide a useful measure
      of the adequacy of regional perfusion and oxygenation in this group of patients.

PMID- 8996014
TI  - Liver function and splanchnic ischemia in critically ill patients.
AB  - STUDY OBJECTIVE: To investigate the concept that splanchnic ischemia leads to
      hepatic dysfunction in the critically ill. DESIGN: Prospective study and analysis
      of patient data. SETTING: A general ICU in an inner-city London teaching
      hospital. PATIENTS: Twenty-seven consecutive critically ill patients with
      evidence of inadequate tissue perfusion requiring pulmonary artery
      catheterization and mechanical ventilation. MEASUREMENTS: In all patients, we
      measured the hepatic metabolism of lidocaine (lignocaine) to
      monoethylglycinexylidide (MEGX) and the clearance of indocyanine green (both
      dynamic, flow-dependent tests of hepatic function) over the first 3 days
      following admission to the ICU. These were compared with results of standard
      liver function tests and related to tonometric assessment of gastric intramucosal
      pH (pHim) and outcome. RESULTS: There were no significant differences in
      bilirubin, aspartate aminotransferase, alkaline phosphatase, and prothrombin
      levels, or in indocyanine green clearance between survivors and nonsurvivors. On
      day 3, the median MEGX level was higher in survivors than in nonsurvivors (16 vs
      2.4 ng/mL, p < 0.001), and the median MEGX level in nonsurvivors fell over the 3
      days (20.6 to 2.4 ng/mL, p < 0.002). MEGX levels were significantly correlated
      with pHim (Spearman rank correlation coefficient [Rs] = 0.69, p < 0.001) as were
      the changes in the two measurements over the 3 days (Rs = 0.46, p < 0.02). The
      MEGX formation test and gastric pHim were the most discriminatory with regard to
      death and survival. CONCLUSIONS: Our findings suggest that critically ill
      patients develop significant hepatic dysfunction that is associated with a poor
      outcome. This is likely to be due to a mismatch between hepatic metabolic demand
      and blood flow, and the MEGX formation test appears to be an extremely effective
      means of assessing liver function and flow in this group of patients.

PMID- 8996015
TI  - Applied PEEP during pressure support reduces the inspiratory threshold load of
      intrinsic PEEP.
AB  - OBJECTIVES: Mechanical ventilation in patients with obstructive airway disease
      (OAD) is associated with the development of dynamic hyperinflation and intrinsic
      positive end-expiratory pressure (PEEPi). One of the effects of this form of
      PEEPi is to act as an inspiratory threshold load that can produce ineffective
      breath triggering, dyspnea, and muscle fatigue. Recently it has been shown that
      applying PEEP in the ventilator circuit can reduce this imposed triggering load.
      We wished to investigate this further by studying patients with OAD being weaned
      with pressure support (PS) ventilation. Our first objective was to determine the
      prevalence and magnitude of this form of PEEPi in OAD patients who were
      clinically judged to be capable of triggering mechanical ventilatory breaths. Our
      second objective was to attempt to reduce the triggering load by applying circuit
      PEEP and then observe the response of patient-ventilator interactions during the
      patient-triggered, pressure-limited PS breath. DESIGN: Thirteen random patients
      with OAD who were receiving PS ventilation were studied by measuring airway
      pressures, airway gas flow, baseline esophageal pressure, esophageal pressure
      time products (PTP), and esophageal pressure changes before ventilator gas
      delivery began (delta Pes taken to represent PEEPi). Measurements were made at
      baseline and after stepwise increases in circuit PEEP up to the PEEPi. RESULTS:
      We found measurable PEEPi in all patients (average +/- SD of 9.54 +/- 4.3 cm H2O)
      and it was > 10 cm H2O in seven patients. As would be predicted, we observed
      progressive reductions in PEEPi as applied PEEP was given. We also observed that
      the component of patient effort (PTP) related to overcoming PEEPi also decreased,
      but the PTP related to tidal volume (VT) did not. The VT associated with the set
      PS thus did not change with application of PEEP, nor did the breathing frequency.
      CONCLUSION: PEEPi is common in OAD patients receiving mechanical ventilatory
      support. The imposed triggering load from PEEPi can be offset to large extent by
      circuit PEEP approaching the baseline PEEPi. Although total patient effort
      substantially falls with applied PEEP, the patient effort that combine with PS to
      effect VT does not.

PMID- 8996017
TI  - Early reperfusion induces alveolar injury in pulmonary embolism.
AB  - STUDY OBJECTIVE: To observe (1) whether the reperfusion is one of the causes
      underlying the development of diffuse alveolar injury following pulmonary
      embolism, and (2) whether polymorphonuclear leukocyte (PMN) accumulation occurs
      in the reperfused lobe, and (3) whether the production of superoxide is increased
      from cells obtained by BAL. DESIGN: The condition of pulmonary embolism was
      simulated by occluding the pulmonary artery branch using a balloon catheter in
      anesthetized closed-chest dogs. The occlusion was maintained for 24 h in the
      occlusion group, and a 2-h period of occlusion was followed by reperfusion in the
      reperfusion group. Histologic examination was performed at 24 h after occlusion
      in both groups (n = 8). Using a different group of dogs (n = 12), local cellular
      changes in the occluded and reperfused lobes were evaluated through BAL performed
      at 1, 2, and 3 h after reperfusion in the reperfusion group and at 3 h after
      occlusion in the occlusion group. Superoxide generation from BAL cells was
      measured by the chemiluminescence method. RESULTS: There was no histologic
      evidence of alveolar injury in the occluded lobe, but there were numerous
      leukocytes and erythrocytes along with exudate and damaged alveoli in the
      reperfused lobe. In the BAL study, the total cell counts recovered by BAL
      remained unchanged in all groups. However, the number of PMNs increased
      significantly in the late stages of reperfusion. Enhanced superoxide generation
      was observed in BAL cells obtained from reperfused lobe. CONCLUSION: Reperfusion
      is one of the causes underlying the development of alveolar injury in pulmonary
      embolism by triggering immigration of PMNs to alveoli, which results in the
      increased superoxide generation in BAL cells.

PMID- 8996016
TI  - Heterogeneous Serratia marcescens genotypes from a nosocomial pediatric outbreak.
AB  - OBJECTIVE: Define the applicability of a rapid molecular typing scheme to study
      the epidemiology of a Serratia marcescens outbreak. DESIGN: With the assistance
      of a simple bacterial lysis technique, isolates of S marcescens from a putative
      outbreak were genotyped with the polymerase chain reaction technology for which
      primers were chosen on the basis of previously defined enterobacterial repetitive
      intergenic consensus sequences. SETTING: Pediatric ICU. PATIENTS: Intensively
      monitored patients who were found to yield S marcescens from any body site during
      the epidemic period. RESULTS: Over an 8-month period, 12 ICU patients were either
      infected or colonized with S marcescens. All of these patients were transiently
      supported by artificial ventilation. During the epidemiologic investigation, a
      dilution error in a high-level glutaraldehyde disinfectant, which was being used
      for some ventilator components, was observed. Rectification of the error was
      associated with an abrupt termination of the outbreak. Enterobacterial repetitive
      intergenic consensus polymerase chain reaction was easily applicable to this
      setting and it defined 4 distinct genotypes among the 12 isolates. CONCLUSION:
      The typing method is easily implemented and offers great promise as an
      epidemiologic tool. The associated investigation served to emphasize that an
      outbreak may occur with more than one epidemic strain and that strain
      heterogeneity itself does not exclude an outbreak.

PMID- 8996019
TI  - Echocardiographic pattern of acute cor pulmonale.

PMID- 8996018
TI  - A comparison of pulmonary availability between Ventolin (albuterol) nebules and
      Ventolin (albuterol) Respirator Solution.
AB  - The two most common albuterol preparations used for nebulization are: (1)
      Ventolin (albuterol) respirator solution (Glaxo Canada Inc; Montreal, Canada) of
      which 2.5 mg (0.5 mL) is diluted with 2 mL of normal saline solution, and (2) the
      preservative-free, prediluted Ventolin (albuterol) Nebules PF (Glaxo) (2.5 mg/2.5
      mL). The two preparations were compared using both a Hudson 1720 "T" up-draft Neb
      U-Mist jet nebulizer and a Hudson 1730 "T" up-draft Neb-U-Mist II jet nebulizer
      (Hudson; Temecula, Calif), which were driven by a compressor (Pulmo-Aide;
      Devilbiss; Somerset, Pa) and by dry compressed air at 6 and 8 L/min. Particle
      size distribution was measured with a particle sizer (Malvern 2600; Malvern
      Instruments; Malvern, UK) and drug output for the nebulizer was calculated from
      the differences in predrug and postdrug volume and concentration. Drug
      availability was defined as the amount of drug carried in particles less than 5
      microns in diameter. Drug availability was greater with the albuterol respiratory
      solution, due to the surface activity of the preservative benzalkonium chloride,
      for both nebulizers but particularly for the 1720. Differences in drug
      availability between nebulizers exceeded fourfold depending on the preparation,
      the nebulizer, and the nebulizing flow. These differences could not have been
      predicted from the manufacturer's specifications. The results suggest that
      prediction of drug availability must be based on measurements with the specific
      preparation and the specific nebulizer used.

PMID- 8996020
TI  - Pharmacologic hemodynamic support in massive pulmonary embolism.

PMID- 8996021
TI  - Work of breathing. The debate continues....

PMID- 8996022
TI  - Thoracoscopic wedge resection of blebs under local anesthesia with sedation for
      treatment of a spontaneous pneumothorax.
AB  - We performed thoracoscopic wedge resections of blebs with a stapling device under
      local anesthesia with sedation in 34 consecutive patients who presented with
      spontaneous pneumothoraces. The indications for surgery included the absence of
      parietal pleural adhesions and knowledge of the precise bleb location prior to
      the procedure. Prior to surgery, 0.5% lidocaine was administered into the pleural
      space, and IV butorphanol tartrate and diazepam were administered to reduce pain
      and anxiety during the procedure. In our series, the thoracoscopic procedure
      resulted in favorable outcomes in all but two patients. There was no evidence of
      hemodynamic instability or arterial blood gas abnormalities encountered during
      the procedure. Minor postoperative complications were seen in only three patients
      (two with air leakage and one with transient atelectasis). One patient had a
      recurrence of his spontaneous pneumothorax 3 months following the procedure.
      Therefore, the overall success rate was 91%. We compared the results of this
      therapeutic modality (group 1) with those of 38 patients who underwent the
      procedure under general anesthesia (group 2) during the same period. The length
      of hospital stay was shorter in group 1 than in group 2 (4.5 +/- 1.3 vs 5.8 +/-
      1.1 days; p < 0.01). Thoracoscopic wedge resections under local anesthesia are
      safe and offer the benefit of shorter hospital stays. We believe that this
      thoracoscopic technique will further simplify the surgical treatment of
      pneumothoraces without incremental risks.

PMID- 8996023
TI  - A 63-year-old woman with weight loss and multiple lung nodules.

PMID- 8996024
TI  - A 60-year-old man with a malignant tumor of the upper airway and unexplained
      respiratory failure.

PMID- 8996025
TI  - Mycobacterium avium complex infection in an immunocompetent young adult related
      to hot tub exposure.
AB  - An unusual case of Mycobacterium avium complex infection occurred in a young
      adult with no preexisting disease and no evidence of immunodeficiency. There was
      diffuse interstitial involvement of the lungs which suggested an active
      alveolitis. Diagnosis required open-lung biopsy. Restriction fragment length
      polymorphism analysis and multilocus enzyme electrophoresis indicated that the
      source of the infection was a hot tub. The infection proved to be exceptionally
      responsive to treatment, and there was complete resolution with a four-drug
      regimen.

PMID- 8996026
TI  - Fatal cases of farmer's lung in a Canadian family. Probable new antigens,
      Penicillium brevicompactum and P olivicolor.
AB  - Three Canadian farmers, including a married couple and another close relative,
      died from progressive pulmonary fibrosis. Their histories and investigations were
      compatible with chronic farmer's lung (FL). Our environmental and immunologic
      studies indicate Penicillium brevicompactum and P olivicolor as probable new
      antigens of FL in a cool and dry climate.

PMID- 8996027
TI  - Succinylcholine-induced hyperkalemia following prolonged pharmacologic
      neuromuscular blockade.
AB  - While being treated for the acute respiratory distress syndrome, a 27-year-old
      woman developed profound hyperkalemia and cardiac arrest following the
      administration of succinylcholine chloride (SCh). She had none of the risk
      factors previously described for development of severe hyperkalemia following SCh
      administrations; however, she had been intermittently treated with
      nondepolarizing neuromuscular blocking drugs throughout the course of her
      illness. We suggest that immobilization of critically ill patients with
      pharmacologic neuromuscular blockade may predispose them to severe hyperkalemia
      and cardiac arrest following administration of SCh. SCh should be used with great
      caution in such patients.

PMID- 8996028
TI  - Primary lymphoepithelioma-like carcinoma of the lung in a child. Report of an
      Epstein-Barr virus-related neoplasm.
AB  - Lymphoepithelioma-like carcinoma (LEC), an undifferentiated carcinoma with
      pronounced lymphocytic infiltration, often is seen in the nasopharynx as well as
      in other areas. But such primary pulmonary lung neoplasms in children are rare,
      and we present the first reported case of primary pulmonary LEC in a child.

PMID- 8996029
TI  - Lung abscess caused by Legionella micdadei.
AB  - We describe a case of lung abscess caused by sporadic infection with Legionella
      micdadei in a patient with AIDS. L micdadei infection can be very difficult to
      diagnose because the organism stains only weakly Gram negative, requires special
      culture media, and is not detectable with some direct fluorescent antibody tests
      that are directed only at Legionella pneumophila. Since it can stain acid fast,
      it may be confused with mycobacteria. The abscess was successfully treated using
      antibiotics and percutaneous catheter drainage.

PMID- 8996030
TI  - Legionella species community-acquired pneumonia.

PMID- 8996031
TI  - That's no lady, revisited.

PMID- 8996032
TI  - Pathologic changes of the trachea after percutaneous dilational tracheostomy.

PMID- 8996033
TI  - Pulmonary hemodynamics and hypoxemia in sleep apnea.

PMID- 8996034
TI  - Osteoporosis in patients undergoing lung transplantation.

PMID- 8996035
TI  - Thrombolysis in the presence of an intracranial meningioma.

PMID- 8996036
TI  - Triaging care for patients with pneumonia. Real progress.

PMID- 8996037
TI  - Advances and stagnations in heart failure.

PMID- 8996038
TI  - Nutrition and asthma.
AB  - Asthma is a syndrome that may have many causes resulting in airway inflammation
      and hyperresponsiveness. The search for the causes of asthma has led to the
      investigation of genetic, atopic, viral, and nutritional factors. For the last 2
      decades, a number of studies have linked particular nutrients to asthma. The
      studies have examined both the suboptimal status of particular nutrients as
      causes of asthma and supplements of specific nutrients as therapy for asthma. We
      reviewed and analyzed data from these studies to determine the role of
      nutritional therapy in the management of asthma. The studies on food allergies
      reveal that IgE-mediated reactions to food are a minor cause of respiratory
      symptoms, affecting more children than adults. Currently, there are no available
      data to support the use of nutritional supplements in the treatment of chronic
      asthma.

PMID- 8996039
TI  - The hospital admission decision for patients with community-acquired pneumonia.
      Results from the pneumonia Patient Outcomes Research Team cohort study.
AB  - BACKGROUND: The hospital admission decision directly influences the magnitude of
      resource use in patients with community-acquired pneumonia, yet little
      information exists on how medical practitioners make this decision. OBJECTIVES:
      To determine which factors medical practitioners consider in making the hospital
      admission decision and which health care services they believe would allow
      ambulatory treatment of low-risk hospitalized patients with community-acquired
      pneumonia. METHODS: Medical practitioners responsible for the hospital admission
      decision for low-risk patients with community-acquired pneumonia were asked to
      describe patient characteristics at initial examination that influenced the
      hospitalization decision, and to identify the health care services that would
      have allowed initial outpatient treatment of hospitalized patients. RESULTS: A
      total of 292 medical practitioners completed questionnaires for 472 (76%) of the
      624 low-risk patients eligible for this study. Although all patients had a
      predicted probability of death of less than 4%, practitioners estimated that 5%
      of outpatients and 41% of inpatients had an expected 30-day risk of death of more
      than 5%. Univariate analyses identified 3 practitioner-rated factors that were
      nearly universally associated with hospitalization: hypoxemia (odds ratio, 173.3;
      95% confidence interval, 23.8-1265.0), inability to maintain oral intake (odds
      ratio, 53.3; 95% confidence interval, 12.8-222.5), and lack of patient home care
      support (odds ratio, 54.4; 95% confidence interval, 7.3-402.6). In patients
      without these 3 factors, logistic regression analysis demonstrated that
      practitioner-estimated risk of death of more than 5% had a strong independent
      association with hospitalization (odds ratio, 18.4; 95% confidence interval, 6.1
      55.7). Practitioners identified home intravenous antibiotic therapy and home
      nursing observation as services that would have allowed outpatient treatment of
      more than half (68% and 59%, respectively) of the patients initially hospitalized
      for treatment. CONCLUSIONS: Practitioners' survey responses suggest that the
      availability of outpatient intravenous antimicrobial therapy and home nursing
      care would allow outpatient care for a large proportion of low-risk patients who
      are hospitalized for community-acquired pneumonia. These data also suggest that
      methods to improve practitioners' identification of low-risk patients with
      community-acquired pneumonia could decrease the hospitalization of such patients.
      Future studies are required to help physicians identify which low-risk patients
      could safely be treated in the outpatient setting on the basis of clinical
      information readily available at presentation.

PMID- 8996041
TI  - Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications.
AB  - BACKGROUND: Little is known about the clinical, diagnostic, and prognostic
      aspects of upper-extremity deep vein thrombosis (UEDVT). OBJECTIVES: To identify
      the clinical and laboratory parameters associated with this disease, to assess
      the diagnostic accuracy of ultrasonographic methods for its detection, and to
      establish the frequency of both early and late complications. PATIENTS AND
      METHODS: After a careful history was taken, 58 consecutive patients with signs
      and symptoms that were clinically suggestive of UEDVT underwent the determination
      of antithrombin III and protein C and S levels and resistance to activated
      protein C and lupuslike anticoagulants. Compression ultrasonography, color flow
      Doppler imaging, and Doppler ultrasonography were performed prior to venography.
      Patients with confirmed UEDVT underwent objective tests to detect a pulmonary
      embolism and were followed up prospectively to record recurrent thromboembolic
      events and postthrombotic sequelae. RESULTS: Findings from venography confirmed
      UEDVT in 27 patients (47%). Central venous catheters, thrombophilic states, and a
      previous leg vein thrombosis were statistically significantly associated with
      UEDVT. Sensitivity and specificity of compression ultrasonography (96% and 93.5%,
      respectively) and color flow Doppler imaging (100% and 93%, respectively) were
      comparable and better than those of Doppler ultrasonography (81% and 77%,
      respectively). Objective findings suggestive of a pulmonary embolism were
      recorded in 36% of the patients with UEDVT. After a mean follow-up of 2 years, 2
      patients with UEDVT experienced recurrent thromboembolic events, and 4 had
      postthrombotic sequelae. CONCLUSIONS: Symptomatic UEDVT is associated with
      central venous catheters, thrombophilic states, and a previous leg vein
      thrombosis. Both compression ultrasonography and color flow Doppler imaging are
      accurate methods for its detection. A pulmonary embolism is a common complication
      of the disease. Finally, this disorder may recur and may be followed by
      postthrombotic sequelae.

PMID- 8996040
TI  - The hospital discharge decision for patients with community-acquired pneumonia.
      Results from the Pneumonia Patient Outcomes Research Team cohort study.
AB  - BACKGROUND: The hospital discharge decision directly influences the length of
      stay in patients with community-acquired pneumonia, yet no information exists on
      how physicians make this decision. OBJECTIVES: To identify the factors physicians
      considered the factors responsible for extending length of hospital stay in
      clinically stable patients, and the outpatient medical services that would allow
      earlier hospital discharge for patients with community-acquired pneumonia.
      METHODS: Physicians responsible for the hospital discharge decision of patients
      with community-acquired pneumonia were asked to identify the factors responsible
      for extending stay in patients hospitalized beyond stability, and the medical
      services that could have allowed earlier hospital discharge to occur. RESULTS:
      For the 418 eligible patients with community-acquired pneumonia identified during
      the study, 332 questionnaires (79%) were completed by 168 physicians. Physicians
      believed 71 patients (22%) were discharged from the hospital 1 day or more
      (median, 2.5 days) after reaching clinical stability. The most common factors
      rated as being "very important" in delaying discharge were diagnostic evaluation
      or treatment of comorbid illness (56%), completion of a "standard course" of
      antimicrobials (15%), and delays with arrangements for long-term care (14%).
      Among the 302 patients with available information on both length of hospital stay
      and stability at discharge, median length of stay was 7.0 days for the 29 low
      risk patients hospitalized beyond reaching clinical stability and 5.0 days for
      the remaining 128 low-risk patients (P < .005); median length of stay was 12.5
      days for the 42 medium- and high-risk patients hospitalized beyond reaching
      clinical stability and 8.0 days in the remaining 113 medium- and high-risk
      patients (P < .001). Frequently cited medical services that "probably" or
      "definitely" would have allowed earlier discharge to occur included availability
      of home intravenous antimicrobial infusion (26%) and home visits by nurses (20%).
      CONCLUSIONS: Physicians believed that diagnostic evaluation or treatment of
      comorbid illness, completion of a standard course of antimicrobial therapy, and
      delays with arrangements for long-term care delayed hospital discharge in
      clinically stable patients. Addressing the efficiency of these aspects of
      inpatient medical care, as well as providing home treatment programs, could
      decrease the length of hospital stay in patients with community-acquired
      pneumonia.

PMID- 8996042
TI  - Fluconazole as prophylaxis against fungal infection in patients with advanced HIV
      infection.
AB  - BACKGROUND: There is limited information regarding the usefulness of primary
      antifungal prophylaxis in patients with advanced human immunodeficiency virus
      (HIV) disease. OBJECTIVE: To evaluate the efficacy and safety of oral fluconazole
      treatment for the prevention of systemic fungal diseases related to the acquired
      immunodeficiency syndrome. METHODS: We evaluated the clinical records of more
      than 1300 HIV-infected patients followed up for 6 years to identify subjects with
      a CD4+ lymphocyte count less than 0.20 x 10(9)/L (200/microL) and no prior
      systemic fungal disease. We compared 128 patients who received oral fluconazole
      (100 mg/d every third week) with 121 subjects who received no antifungal
      treatment. MAIN OUTCOME MEASURES: The occurrence of visceral mycoses or death was
      considered an end point. The frequency of esophageal candidiasis and
      extrapulmonary cryptococcosis and their related clinical and laboratory features,
      as well as overall patient survival, were assessed and compared between the 2
      study groups. RESULTS: Subjects not treated with fluconazole experienced a
      significantly higher incidence of systemic mycoses than patients who received
      fluconazole: 28.4 vs 8.8 cases per 100 patient-years (P < .001). Fluconazole
      treatment was more effective in preventing esophageal candidiasis than
      cryptococcosis and was more effective in subjects with a CD4+ cell count less
      than 0.10 x 10(9)/L. Moreover, fungal complications occurred later and were
      associated with a significantly lower CD4+ cell count among treated vs untreated
      patients, while the duration of antiretroviral therapy did not play a significant
      role. Although mortality rates were similar in the 2 study groups, the fatal
      outcome of disease was less frequently caused by a fungal disease in subjects who
      underwent fluconazole prophylaxis. Fluconazole had a favorable tolerability
      profile. CONCLUSIONS: In our experience, primary fluconazole prophylaxis proved
      safe and effective in the prevention of systemic candidiasis and cryptococcosis
      in patients with advanced HIV disease but it did not improve overall survival.
      Prospective controlled trials are advisable to confirm efficacy, to find the drug
      of choice and its best dosage and schedule of administration, to identify patient
      subgroups showing the most favorable cost-benefit ratios, and to evaluate the
      effects on overall life expectancy and the risk of emergence and spread of
      antifungal drug resistance.

PMID- 8996043
TI  - Functional status among survivors of in-hospital cardiopulmonary resuscitation.
      SUPPORT Investigators Study to Understand Progress and Preferences for Outcomes
      and Risks of Treatment.
AB  - OBJECTIVES: To describe functional outcomes of seriously III patients who
      survived 2 months after in-hospital cardiopulmonary resuscitation (CPR) and to
      identify patient and clinical characteristics associated with worse functional
      status after CPR. METHODS: Multicenter prospective observational analysis of 162
      seriously ill hospitalized patients who survived 2 months after CPR. Analysis of
      clinical characteristics associated with worse functional outcome. RESULTS: Among
      162 survivors of in-hospital CPR, 56% had the same or improved function and 44%
      had worse function at 2 months compared with functional status before CPR.
      Patients with worse function deteriorated by a mean of 3.9 activities of daily
      living and were less likely to survive to hospital discharge (P < .001) or to 6
      months after study entry (P < .001). Worse functional outcome was associated with
      greater age and longer hospital stay before CPR. CONCLUSIONS: More than half of
      CPR survivors had preserved functional status 2 months after CPR. However,
      patients with worse function are profoundly disabled. In anticipation of possible
      severe disability after CPR, preferences for care in such health states should be
      discussed with patients before the need for CPR, particularly among older
      patients and those with long hospital stays.

PMID- 8996044
TI  - Prospective study of moderate alcohol consumption and mortality in US male
      physicians.
AB  - BACKGROUND: Although moderate alcohol consumption decreases the risk of
      myocardial infarction, its impact on all-cause mortality among apparently healthy
      men is unclear. METHODS: We performed a prospective cohort study in 22071 men in
      the Physicians' Health Study. Participants were aged 40 to 84 years and had no
      history of myocardial infarction, stroke, transient ischemic attack, or cancer.
      RESULTS: There were 1206 deaths (394 cardiovascular, 488 cancer, and 324 other)
      during 10.7 years of follow-up. Compared with participants who consumed less than
      1 drink per week, the relative risk (95% confidence interval) of all-cause
      mortality for men who consumed 2 to 4 drinks per week was 0.72 (0.59-0.87); 5 to
      6 drinks per week, 0.79 (0.64-0.99); 1 drink per day, 0.98 (0.84-1.15); and the
      highest drinking group (> or = 2 drinks per day), 1.51 (1.17-1.95). This
      association was similar with either nondrinkers or occasional drinkers used as
      the reference group and was not subject to material confounding or effect
      modification by any factor examined. The overall relationship was the result of a
      J-shaped association with cardiovascular mortality, an increase in cancer deaths
      for the highest drinking group, and a U-shaped association with other causes of
      mortality. CONCLUSIONS: Risk of all-cause mortality varies by level of alcohol
      consumption. In this apparently healthy cohort, men who consumed 2 to 6 drinks
      per week had the most favorable mortality profile and men who had 2 or more
      drinks per day the most unfavorable mortality profile. The difference between
      consumption of small and large amounts of alcohol may mean the difference between
      preventing and causing excess mortality.

PMID- 8996045
TI  - Pharmacoeconomic comparison of treatments for the eradication of Helicobacter
      pylori.
AB  - BACKGROUND: Patients with Helicobacter pylori-induced duodenal ulcer should have
      their infection eradicated. The optimal choice of antibiotic therapy, however, is
      less clear. OBJECTIVE: To evaluate costs and outcomes of treatment with 8
      antibiotic regimens with documented activity against H pylori vs maintenance
      therapy with histamine2-receptor antagonists (H2RA). METHODS: A meta-analysis for
      119 studies enrolling 6416 patients to determine aggregate eradication rates. The
      complexity of each regimen was used to determine the anticipated compliance rate
      and actual effectiveness. A decision analytic model with Monte Carlo simulation
      determined annual costs and health outcomes. RESULTS: Average annual total costs
      of testing for H pylori infection and antibiotic treatment ranged from $223 to
      $410 and prevented ulcer recurrence in 70% to 86% of patients. The H2RA
      maintenance therapy cost $425 and prevented recurrence in 72% of patients. The
      lowest costs and recurrence rates were achieved by 3 regimens: standard triple
      therapy (a combination of bismuth subsalicylate, metronidazole, and tetracycline
      hydrochloride) for 14 days ($223, with 18% recurrence); a combination of
      clarithromycin, metronidazole, and a proton pump inhibitor for 7 days ($235, with
      15% recurrence); and standard triple therapy with a proton pump inhibitor for 7
      days ($236, with 14% recurrence). CONCLUSION: Treatment with any regimen resulted
      in lower costs compared with H2RA maintenance therapy. Three antibiotic regimens
      had consistently lower costs and better outcomes: standard triple therapy for 14
      days, metronidazole, clarithromycin, and a proton pump inhibitor for 7 days, and
      standard triple therapy plus a proton pump inhibitor for 7 days.

PMID- 8996046
TI  - Readmission after hospitalization for congestive heart failure among Medicare
      beneficiaries.
AB  - BACKGROUND: Congestive heart failure is the most common discharge diagnosis for
      Medicare beneficiaries. While several single-center studies have suggested that
      these patients are particularly vulnerable to readmission, no recent study, to
      our knowledge, has reported the readmission rates for a large number of elderly
      patients with congestive heart failure across a diverse spectrum of hospitals.
      OBJECTIVES: To define the readmission rate for elderly patients discharged after
      an episode of congestive heart failure. To determine the spectrum of diagnoses
      that are responsible for readmissions among patients with congestive heart
      failure. To identify patient and hospital characteristics associated with a
      higher likelihood of readmission. METHODS: This observational study, using
      Medicare administrative files, evaluated readmission and death among all
      survivors of a hospitalization in Connecticut for congestive heart failure from
      fiscal year 1991 through fiscal year 1994. RESULTS: There were 17448 survivors of
      a hospitalization for congestive heart failure during the study period. In the 6
      months following the index admission, 7596 patients (44%) were readmitted to a
      hospital at least once. Congestive heart failure was the most frequent reason for
      readmission among study patients, accounting for 18% of all readmissions. In the
      multivariable analysis, significant predictors of readmission included male sex
      (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.05-1.20), at least 1
      prior admission within 6 months of the index admission (OR, 1.64; 95% CI, 1.53
      1.77), Deyo comorbidity score of more than 1 (OR, 1.56; 95% CI, 1.45-1.68), and
      length of stay in the index hospitalization of more than 7 days (OR, 1.32; 95%
      CI, 1.24-1.41). While age was not a significant predictor of readmission, it
      became significant in a model with the combined outcome of readmission or death
      as the dependent variable. CONCLUSION: Readmission after a hospitalization for
      congestive heart failure is common among Medicare beneficiaries, with almost half
      of the patients readmitted within 6 months. This striking rate of readmission in
      a common diagnosis demands efforts to further clarify the determinants of
      readmission and develop strategies to prevent this adverse outcome.

PMID- 8996047
TI  - Musculoskeletal pain as an indicator of occult malignancy. Yield of bone
      scintigraphy.
AB  - BACKGROUND: When musculoskeletal pain is persistent or out of proportion to
      clinical findings, diagnostic imaging is often used to evaluate for the presence
      of occult pathologic conditions. OBJECTIVE: To examine the efficacy of bone
      scintigraphy for identifying occult malignancy in such patients. METHODS: Bone
      scans of 491 patients with new or recurrent complaints of musculoskeletal pain
      and no previously known malignancy were retrospectively reviewed. The findings of
      each scan were classified into 1 of the following categories: (A) no evidence of
      malignancy; (B) equivocal (1-3 lesions of uncertain significance); or (C)
      probable metastatic disease (> 3 lesions without trauma or other benign
      explanation). All diagnoses of malignancy established within 6 months of the bone
      scan were then determined from review of radiological and clinical records.
      RESULTS: The distribution of scan interpretations was as follows: category A, 386
      (79%); category B, 84 (17%); and category C, 21 (4%). Among the 181 patients
      younger than 50 years, 161 (89%) had category A and 20 (11%) had category B
      scans. Of the 310 patients aged 50 years or older, 226 (73%) had scans in
      category A, 64 (21%) in category B, and 21 (7%) in category C. Thirty patients
      (6%) had malignancy involving bone, 29 among those aged 50 years or older. In
      patients aged 50 years or older, 10 (16%) of 64 with equivocal scan findings
      (category B) and 19 (90%) of 21 with widespread abnormalities (category C) had
      malignancy involving bone. Initial radiographs of symptomatic sites showed lytic
      or blastic bone abnormalities suggestive of malignancy in 16 (59%) of the 29
      older patients in whom this diagnosis was confirmed. CONCLUSIONS: In patients
      aged 50 years or older, the yield of bone scintigraphy for identification of
      occult malignancy (29/310; 9%) is sufficient to justify its use in the
      investigation of the cause of problematic bone or musculoskeletal symptoms.

PMID- 8996048
TI  - Failure of cooking to prevent shellfish-associated viral gastroenteritis.
AB  - BACKGROUND: In January 1995, Florida experienced the largest outbreak of oyster
      associated gastroenteritis ever reported. METHODS: We interviewed both the cohort
      of persons from 38 gatherings where illness was reported and a sample of
      harvesters and harvest-area residents. Oysters were traced by means of tags and
      dealer records, and water quality measures in harvest areas were reviewed. We
      examined stool specimens for small round structured viruses by means of electron
      microscopy and amplification of RNA by reverse-transcriptase polymerase chain
      reaction. We also tested serum specimens for antibodies to Norwalk virus.
      RESULTS: Of 223 oyster eaters, 58% (129/223) became ill, compared with 3% (2/76)
      of non-oyster eaters (relative risk, 22; 95% confidence interval, 5.6-87.0). Most
      oyster eaters (67% [149/223]) ate only cooked (grilled, stewed, or fried)
      oysters. Oyster eaters who reported eating only thoroughly cooked oysters were as
      likely to become ill as those who ate raw oysters (relative risk, 0.68; 95%
      confidence interval, 0.45-1.0; P = .1). In 29 clusters, implicated oysters were
      from Apalachicola Bay, Florida. A community outbreak occurred in 2 bayside
      communities before the oyster harvest, leading to an increase in the reportedly
      common practice of overboard dumping of feces. Small round structured viruses
      were identified in the stool specimens of 2 harvest-area residents and 9 persons
      from 8 clusters. Results of water quality tests for fecal coliforms were within
      acceptable limits. CONCLUSIONS: This large outbreak of gastroenteritis associated
      with oysters may have resulted from overboard dumping of feces during a community
      outbreak of diarrheal illness. Our findings of acceptable water quality measures
      for fecal contamination and the lack of appreciable protective effect from
      cooking leave the consumer with no assurance of safety.

PMID- 8996049
TI  - African tick-bite fever. An imported spotless rickettsiosis.
AB  - OBJECTIVES: To characterize the clinical presentation and course of African tick
      bite fever, a recently rediscovered rickettsiosis caused by Rickettsia africae (a
      new species within the spotted fever group of rickettsiae), to establish its
      relationship with Amblyomma tick species, and to discuss its role in the etiology
      of fever in patients who are returning from the tropics. PATIENTS: Seven patients
      who returned from Zimbabwe of the Republic of South Africa and presented with
      fever. METHODS: Cases were recognized clinically by the presence of multiple
      taches noire and were diagnosed as having a rickettsial infection by
      identification of the organisms in circulating endothelial cells. The causative
      role of R africae was further demonstrated using cross-absorption and
      immunoblotting of patients' serum samples and isolation of the agent from blood
      and skin biopsy specimens. Isolates were characterized using the restriction
      fragment length polymorphism-polymerase chain reaction and sequence analysis of
      the gene that encodes for the 190-kd Rickettsia-specific antigen. RESULTS: All 7
      patients presented with fever and multiple taches noire. Further physical
      examination of patients revealed lymphadenopathy, lymphangitis, and edema, but
      there were virtually no signs of a rash. These findings are characteristic of R
      africae-infected patients and are distinct from those observed in patients with
      Rickettsia conorii-induced Mediterranean spotted fever. All 7 patients were
      infected with R africae as demonstrated by immunoblotting or isolation of the
      agent, and all were cured. CONCLUSIONS: With increasing international travel, a
      need for the recognition of rickettsial diseases by physicians is becoming more
      important. Tick-bite fever, a disease caused by R africae and transmitted by
      Amblyomma ticks, is characterized by multiple taches noire, lymphadenopathy,
      lymphangitis, and edema, but no rash or a discrete rash. It is a frequent but
      benign disease that physicians should consider when presented with febrile
      patients returning from southern Africa.

PMID- 8996050
TI  - Is the course of neurocysticercosis modified by treatment with anthelmintic
      agents?

PMID- 8996051
TI  - Psychosocial interventions in coronary artery disease.

PMID- 8996052
TI  - Antibiotic prophylaxis for bacterial endocarditis: an evolving story with new
      paradigms.

PMID- 8996053
TI  - Hepatic pulsations in a patient with cholangiocarcinoma.

PMID- 8996054
TI  - Beyond do-not-resusitate orders: a house staff mentoring and credentialing
      project on advance directives.

PMID- 8996055
TI  - Zamboni disease.

PMID- 8996056
TI  - George Adlington Syme Oration. Surgery: a suitable career for women?

PMID- 8996057
TI  - Cell adhesion molecules and colon cancer.
AB  - There is a general consensus that cell-cell and cell-matrix interactions
      determine, at least in part, the behaviour of colon cancer. The biological
      mediators responsible for these interactions are cell adhesion molecules
      belonging to several major receptor families called integrins, cadherins, the
      immunoglobulin superfamily, hyaluronate receptors and mucins. Emerging data
      indicate that certain patterns of adhesion receptor expression are associated
      with more aggressive disease. The present review examines the role of each of the
      receptor families in the development and progression of large bowel cancer.

PMID- 8996058
TI  - Thirty years experience with heart valve surgery: isolated aortic valve
      replacement.
AB  - BACKGROUND: Thirty years have elapsed since the commencement of open-heart
      surgery in South Australia. A retrospective study was performed to evaluate
      mortality and complication rates and to identify factors associated with poor
      outcomes in all patients who underwent prosthetic aortic valve replacement during
      this period. METHODS: Questionnaires and personal contact have been used to
      generate a combined database of pre-operative and post-operative information and
      long-term follow-up on 1322 patients who underwent isolated prosthetic aortic
      valve replacement at the Cardio-Thoracic Surgical Unit of the Royal Adelaide
      Hospital between 1963 and 1992. RESULTS: Complete survival follow-up data were
      obtained for 94% (1241) of the patients. The Bjork-Shiley valve was used in 66%
      (875) of the patients, a Starr-Edwards prosthesis in 31% (412), a St Jude
      prosthesis in 2% (26), and only 0.7% (9) bioprosthetic valves were inserted. The
      hospital mortality rate for the 30-year period was 2.9%. Progressively older and
      less fit patients have undergone surgery in recent years. The long-term survival
      of patients with aortic stenosis and aortic incompetence was not significantly
      different. Long-term survival was significantly shorter for patients with higher
      New York Heart Association (NYHA) functional classifications, and for patients in
      pre-operative atrial fibrillation. Pre-operative dyspnoea was significantly
      improved following aortic valve replacement. The rates of postoperative
      haemorrhagic and embolic complications were low by comparison with other
      published series. CONCLUSIONS: Aortic valve replacement can be performed with low
      hospital mortality and complication rates, and significant symptomatic
      improvement can be expected. Aortic valve recipients have a favourable prognostic
      outcome compared with an age- and sex-matched population, and risk factors that
      determine long-term survival can be identified pre-operatively.

PMID- 8996059
TI  - Thirty years experience with heart valve surgery: isolated mitral valve
      replacement.
AB  - BACKGROUND: Thirty years have elapsed since the commencement of open-heart
      surgery in South Australia. A retrospective study was performed to evaluate
      mortality and complication rates and to identify factors associated with poor
      outcomes in all patients who underwent prosthetic mitral valve replacement during
      this period. METHODS: Questionnaires and personal contact have been used to
      generate a combined database of pre-operative and post-operative information and
      long-term follow-up on 938 patients who underwent isolated prosthetic mitral
      valve replacement at the Cardio-Thoracic Surgical Unit of the Royal Adelaide
      Hospital between 1963 and 1993. RESULTS: Complete survival follow-up data were
      obtained for 92% (865) of the patients. The Starr-Edwards valve was used in 95%
      (891) of the patients, a Bjork-Shiley prosthesis in 2.5% (23) of the patients,
      and only 24 (2.5%) other valves were inserted. The hospital mortality rate for
      the 30-year period was 4.7%. The mean age of the patients who underwent surgery
      was greater in each of the three successive decades. A long-term survival
      advantage was observed for patients with mitral stenosis, however, survival was
      significantly shorter for patients with higher New York Heart Association (NYHA)
      functional classifications and for patients in pre-operative atrial fibrillation.
      Pre-operative dyspnoea was significantly improved following mitral valve
      replacement. The rates of postoperative haemorrhagic and embolic complications
      were low by comparison with other published series. CONCLUSION: Mitral valve
      recipients do not regain a normalized life expectancy, but risk factors that
      determine long-term survival can be identified pre-operatively to aid appropriate
      patient selection.

PMID- 8996060
TI  - Gastric cancers in Singapore: poor prognosis arising from late presentation.
AB  - BACKGROUND: Mortality rates from gastric cancer, apart from those derived from
      Japanese series, remain poor. This paper sought to determine the present outcome
      of gastric carcinoma in a predominantly Chinese population in Singapore.
      Prognostic factors useful in predicting survival were also evaluated in this
      population. METHOD: All cases of histologically confirmed gastric adenocarcinoma
      presenting in 1992 were entered into a prospective database. Prognostic factors
      related to age, sex, site of disease, depth of invasion, histological grade,
      nodal status and stage of disease were evaluated in patients with resectable
      disease to determine their utility in predicting survival. RESULTS: Of 131
      consecutive patients with histologically proven adenocarcinomas, 37% had distant
      metastases at presentation predominantly in the liver (21%) and peritoneal cavity
      (20%). Sixty-four per cent of patients underwent surgery and in only 51% of these
      patients was resection of the tumour possible. Stages III and IV (T4N2) locally
      advanced disease were present in 38% of patients. Thus the majority of patients
      presented with late or metastatic disease (75%, stages III and IV). Sixty per
      cent of patients were alive at 1 year and 40% at 2 years after resection of the
      tumour (Kaplan-Meier survival plots). In contrast, no patient survived longer
      than a year if the tumour was not resectable (P < 0.001, log-rank test). Median
      survival of patients without surgery was 12 weeks. Median survival for patients
      with resected stage IV disease was 23 weeks, compared to 18 weeks after surgical
      bypass. Age, sex, site, depth of invasion and histological grade did not
      significantly predict survival. Patients with node-negative disease survived
      longer (2 years. 70%) than those with nodal involvement (2 years, 44%: P = 0.06,
      log-rank test). Pathologic staging with the TNM system was useful in predicting
      survival (P < 0.001). Sixty per cent of patients with stage I and II disease were
      alive at 2 years compared to 54% with stage III disease and 0% with stage IV
      disease. CONCLUSION: The prognosis of stomach cancer remains poor, due
      predominantly to late presentation. Pathologic TNM staging and nodal status were
      useful in predicting survival outcome after resection. If the tumour were
      resectable, survival was appreciable even in patients with advanced stage III (2
      years. 54%) and stage IV (1 year, 40%) disease. Strategies to improve outcome
      should focus on early detection of gastric carcinomas.

PMID- 8996061
TI  - Major upper gastrointestinal haemorrhage associated with hepatic arterial
      chemoperfusion.
AB  - BACKGROUND: The present study reviews the nature of upper gastrointestinal
      complications of hepatic arterial chemoperfusion at a tertiary referral centre
      for the treatment of hepatic malignancy. METHODS: The patients involved in the
      present study all had major upper gastrointestinal (GI) haemorrhage and were
      undergoing hepatic arterial chemoperfusion. RESULTS: Eight patients had major
      upper GI haemorrhage. Three of these patients were not referred for surgical
      management, and all three patients died. The five patients who were admitted or
      transferred to our unit and who underwent surgery all survived. CONCLUSIONS:
      These complications are probably caused by extravasation of 5-fluorouracil (5-FU)
      following thrombosis of the gastroduodenal artery. The resulting cavity may
      perforate into the hepatic artery, portal vein, duodenum or biliary tree.
      Surgeons and oncologists should be aware of these complications. If upper
      abdominal pain occurs, chemoperfusion should cease immediately and an urgent
      investigation, which may include catheter angiography, gastroscopy and computed
      tomography (CT) scanning, should be carried out to exclude an hepatic artery
      pseudo-aneurysm.

PMID- 8996062
TI  - Morbidity and mortality after single- and double-stapled colorectal anastomoses
      in patients with carcinoma of the rectum.
AB  - BACKGROUND: The optimal method of restoring intestinal continuity after rectal
      resection has been controversial. This study aims to compare the morbidity,
      mortality and survival of patients having either single-stapled (SS) or double
      stapled (DS) colorectal anastomoses following resection of the rectum for cancer.
      METHODS: Peri-operative and long-term follow-up data were prospectively
      documented in all patients undergoing rectal resection for carcinoma with a
      stapled anastomosis at our institution over a 14-year period. Patients were
      stratified by anastomotic technique (SS or DS). Peri-operative mortality,
      complications potentially related to anastomotic technique and cancer-related
      outcome were compared. RESULTS: Two hundred and thirty-five patients had SS and
      65 patients had DS anastomoses. The groups were well matched for age, sex, and
      tumour stage. Double-stapled anastomoses were used more frequently in the distal
      third of the rectum (P < 0.001). The distal margin of resection was not
      influenced by anastomotic technique. Major anastomotic leakage in 2.9% of SS
      cases was not significantly different from 6.1% of DS cases, and leakage was not
      influenced by anastomotic technique at any given level of the rectum. Two-year
      local recurrence rates were not significantly different between groups (SS 3.5%;
      DS 5.9%). CONCLUSIONS: These results suggest that the double-stapling technique
      is as safe as the single-stapling technique for constructing an anastomosis after
      excision of the rectum for cancer, in terms of the risk of leakage, the
      development of an anastomotic stricture, or local recurrence.

PMID- 8996063
TI  - Vesico-ureteric reflux and surgically treated pelvi-ureteric junction obstruction
      in infants under the age of 12 months.
AB  - BACKGROUND: Pelvi-ureteric junction obstruction has been increasingly diagnosed
      in infants, mostly as a consequence of antenatal ultrasound examinations.
      METHODS: Of 55 infants below the age of 12 months who underwent dismembered
      pyeloplasty over a 7-year period, we aimed to determine the patterns and outcome
      of associated vesico-ureteric reflux that was present in 15 (28%) of the 53
      infants in whom follow-up was available. RESULTS: A total of eight infants had
      resolution of their reflux with conservative management and the median time to
      resolution was 15 months. Five infants proceeded to ureteroneocystotomy.
      CONCLUSIONS: Given the association of vesico-ureteric reflux and pelvi-ureteric
      junction obstruction, routine cystography is recommended when the diagnosis of
      pelvi-ureteric junction obstruction is made.

PMID- 8996064
TI  - Early clinical experience with continent urinary diversion.
AB  - BACKGROUND: Alternatives to cutaneous diversion have included continent urinary
      diversion and replacement cystoplasty. Five-year experience with continent
      diversion is reported. METHODS: Between 1989 and 1994, 29 patients underwent
      continent urinary diversion. Of these, 24 patients underwent Indiana pouch
      procedures and five patients had a Mitrofanoff-type procedure. All have now been
      followed up for at least 12 months. RESULTS: The continence rate for the Indiana
      pouch group was 23/24 (96%) and the mean capacity was 648 mL (range 300-1400).
      There were nine (37.5%) early postoperative complications, only three of which
      (12.5%) required surgical revision. The late complication rate was 35.5% (7/22),
      and 18.2% (4/22) of the patients underwent re-operation. Stomal stenosis occurred
      in two patients in whom the stoma was situated in the right iliac fossa, whereas
      all 12 stomas sited at the umbilicus had no stomal problem. Four of the five
      patients having Mitrofanoff procedures were continent, but these patients had
      higher rates of early and late complications. CONCLUSIONS: From this experience,
      the Indiana pouch urinary diversion appears to be superior to the Mitrofanoff
      procedure when continent diversion is indicated. An umbilical stoma site is
      optimal.

PMID- 8996065
TI  - Suture haemorrhoidectomy: a day-only alternative.
AB  - BACKGROUND: Haemorrhoidectomy is a common treatment for third degree symptomatic
      haemorrhoids, and day surgery has increased because of increasing pressure for
      hospital beds. The aim of the present study is to describe a technique of suture
      haemorrhoidectomy (SH), conducted as a day-only procedure, and compare the
      effectiveness and outcomes of this method with the conventional Milligan-Morgan
      haemorrhoidectomy (MMH). METHODS: The results of 18 consecutive patients, mean
      age 52 years (31-73) undergoing SH between April 1994 and June 1995 were compared
      with a historical control group of 17 consecutive patients, mean age 45 years (29
      72), who had MMH in the preceding year. Seven patients were excluded because of
      intercurrent anal pathology (1), thrombosed haemorrhoids (1) or loss to follow-up
      (5). An interviewer followed up patients using a telephone questionnaire.
      RESULTS: Mean follow-up was 6 months in the SH group and 18 months in the MMH
      group. There was no significant difference in total operative time. The SH group
      had a significantly shorter mean time to first void of 3 h versus 11 h (P <
      0.005), mean time to first bowel action of 11 h versus 48 h (P < 0.005) and mean
      in-hospital stay of 10 h versus 77 h (P < 0.005). The SH group had a
      significantly decreased linear analogue pain scale, a mean of 1 versus 3 (P <
      0.05). The complications were: two readmissions for pain relief in the SH group
      and urinary retention in one MMH patient. None of the study group have had
      recurrence of haemorrhoids. CONCLUSION: Suture haemorrhoidectomy as a day-only
      procedure is safe, less painful and reduces in-hospital admission time. The long
      term effectiveness and complications of the technique are as yet undetermined.

PMID- 8996066
TI  - John Wilkins, surgeon, 1826-1905: experiences in Williamstown (Melbourne) and New
      Zealand.
AB  - John Wilkins was a prominent colonial surgeon for 15 years in Williamstown,
      Victoria. During the early gold rushes he prospered from investments in property.
      In Melbourne he aimed to become a recognized authority in diseases of the eye and
      throat, but he did not achieve his aims, and caused bitterness in the medical
      community by advertising. After 10 years he moved to Dunedin where he produced
      the first publication on anaesthesia in New Zealand. He moved to Christchurch,
      but found contentment in Auckland where he practised general medicine with
      special consultations in general surgery and diseases of the eye, ear, nose and
      throat, and where he lived for the remainder of his life.

PMID- 8996067
TI  - Laparoscopic versus open appendicectomy.

PMID- 8996069
TI  - Massive pancreatic duct haemorrhage.
AB  - Direct fistula between the splenic, artery and the pancreatic duct is briefly
      reviewed. The literature indicates that such a fistula is almost always due to a
      pancreatic artery aneurysm. Because of diagnostic difficulties, a variety of
      operations have been performed on these patients prior to arriving at the correct
      diagnosis. A patient's history of direct fistula between the splenic artery and
      the pancreatic duct, causing recurrent haemorrhage and eventual death from
      massive blood loss, is described. Unlike other reported cases, this was not
      associated with an angiographically demonstrable aneurysm of the splenic artery.
      Treatment by distal pancreatectomy or radiologically guided pancreatic artery
      embolization is discussed.

PMID- 8996068
TI  - Prevention of infection in a patient with chronic idiopathic neutropenia
      undergoing coronary bypass surgery with peri-operative G-CSF.
AB  - The prevention of postoperative infection complications in a patient with chronic
      idiopathic neutropenia treated with granulocyte colony stimulating factor (G-CSF)
      is reported. A 48-year-old woman who presented with chronic idiopathic
      neutropenia causing life-long recurrent infections, and postoperative suppurative
      wound infections, presented for elective coronary artery surgery. The patient was
      successfully treated with G-CSF, resulting in a significantly higher neutrophil
      count and no infection complications in the peri-operative period. Peri-operative
      G-CSF therapy in patients with chronic idiopathic neutropenia is effective in
      increasing the total neutrophil count, and decreasing infection complications.

PMID- 8996070
TI  - Bilateral primary lymphoma of the breast.

PMID- 8996071
TI  - Traumatic aneurysms of the carotid arteries.

PMID- 8996072
TI  - Postpartum avulsion of the terminal ileal wall in Crohn's disease.
AB  - A case of acute perforation of the terminal ileum induced by avulsion of the
      bowel wall in a segment of acutely inflamed Crohn's disease is presented. This
      case is unusual in that the avulsion developed after delivery following the rapid
      retraction of the uterus which had been compressing a small localized perforation
      and abscess. A review of the literature has failed to demonstrate a similar case
      report.

PMID- 8996073
TI  - Beware the undescended testis and abdominal mass.
AB  - We report five patients who presented with seminoma of an undescended testis to
      highlight the importance of dealing with adult cryptorchidism. On the basis of
      the literature review and our experience, we advocate orchidectomy for post
      pubertal cryptorchid patients of any age because follow-up may be difficult, and
      treatment for the tumour may be unsuccessful.

PMID- 8996074
TI  - Spontaneous thrombosis of the internal jugular vein as the initial presentation
      of the primary antiphospholipid syndrome.

PMID- 8996075
TI  - Giving life to numbers.
AB  - The yearly cancer statistics article represents a snapshot of the evolving trends
      in cancer events, providing a reference point for evaluating the successes and
      failures of cancer control in the United States. Dr. Cunningham, President of the
      American Cancer Society and a Surgical Oncologist at St. Francis Hospital in
      Evanston, Illinois, provides an overview of important observations from this
      year's data, including the observation that for the first time overall cancer
      mortality is following a downward trend in the United States.

PMID- 8996077
TI  - Tumor-related prognostic factors for breast cancer.
AB  - Interest in prognostic factors for breast cancer has been stimulated by the
      success of systemic adjuvant therapy for early-stage operable disease. Patients
      destined for recurrence can be selected for systemic adjuvant therapy, while
      patients not likely to recur can be spared the morbidity of unnecessary
      treatment. The number of tumor-related features available for prognosis has grown
      impressively in recent years. The purpose of this article is to review tumor
      related biologic factors and relate them to prognosis and treatment objectives.

PMID- 8996076
TI  - Cancer statistics, 1997.

PMID- 8996078
TI  - Pathobiological considerations relating to the treatment of intraductal carcinoma
      (ductal carcinoma in situ) of the breast.
AB  - Management of ductal carcinoma in situ has become one of the most controversial
      topics in breast disease. While mastectomy has been the traditional treatment,
      many now feel it is excessive in most cases. As a result, a great effort has been
      made to identify pathobiological characteristics of DCIS that can be used to
      stratify appropriate treatment decisions. This article reviews efforts to relate
      pathobiological characteristics to disease management and provides treatment
      recommendations based on the latest evidence.

PMID- 8996079
TI  - Isolation and promoter mapping of the gene encoding murine co-stimulatory factor
      B7-1.
AB  - B7-1 is one of the co-stimulatory factors which plays an important role in
      immunity. We have cloned and functionally mapped the promoter of the murine B7-1
      gene using transient transfection assays in mouse L (tk-) cells. The B7-1 basal
      promoter consists of three positively regulated regions. The distal region,
      located at -2597 to -1555, contains an assortment of putative transcription
      factor binding sites. The proximal upstream region, located at -130 to -110,
      contains a tandem repeat sequence 5'-GTGTTCTAGTGTT-3'. A downstream region is
      positioned at +269 to +25. We have also identified an alternatively spliced form
      of the murine B7-1 gene in L (tk-) cells.

PMID- 8996080
TI  - Mammalian homologues of yeast vacuolar protein sorting (vps) genes implicated in
      Golgi-to-lysosome trafficking.
AB  - Sec1p, Vps33p, Vps45p and Sly1p constitute a family of proteins implicated in
      vesicle trafficking at distinct stages of the yeast secretory pathway. Several
      mammalian homologues of Sec1p have been described, including n-sec1 which has
      been implicated in the regulation of synaptic vesicle docking at the nerve
      terminal. We have characterized cDNA clones encoding three additional mammalian
      homologues belonging to this family: r-vps33a and r-vps33b from rat, which are 30
      and 26% identical to yeast Vps33p, respectively, and h-vps45 from human which is
      38% identical to yeast Vps45p at the amino acid (aa) level. Phylogenetic analysis
      of 16 Sec1p-related proteins from several species is consistent with the
      hypothesis that the evolution of this gene family parallels the specialization of
      vesicle trafficking to distinct intracellular compartments. By Northern analysis,
      each of these genes is expressed in all tissues examined (brain, spleen, lung,
      liver, skeletal muscle, kidney, testis). While n-sec1 binds syntaxin 1a, 2, and
      3, r-vps33a, r-vps33b and h-vps45 do not bind any of the known syntaxins. We
      propose that the three proteins bind as yet unidentified syntaxin homologues
      involved in vesicle trafficking between the Golgi apparatus, prelysosomal
      compartment(s), and the lysosome.

PMID- 8996081
TI  - Total modification of the bacteriophage lambda tail tube major subunit protein
      with foreign peptides.
AB  - The bacteriophage lambda has been shown previously to tolerate a high
      multiplicity of peptide additions to the C-terminus of the major tail tube
      subunit protein (gpV, the product of the V gene). However, it was not clear
      whether all gpV copies within a functional virion could tolerate such
      modification. Complementation tests with phage bearing either V gene amber
      mutations or a precisely deleted V gene were used to test the extent of possible
      tail tube peptide display. Expression of plasmid-encoded gpV fused C-terminally
      with certain foreign peptides allowed rescue of such V gene-defective phage to
      essentially wild-type levels. After extensive purification such phage were shown
      by sensitive Western blotting to contain only the modified form of gpV. Peptide
      modified gpV could also form indefinite tail tube polymeric structures
      (polytubes).

PMID- 8996082
TI  - The cpsABCDE genes involved in polysaccharide production in Streptococcus
      salivarius ssp. thermophilus strain NCBF 2393.
AB  - A 4074-bp EcoRI fragment of Streptococcus salivarius ssp. thermophilus (S.
      thermophilus) chromosomal DNA containing genes involved in exocellular
      polysaccharide (EPS) was identified and cloned. The nucleotide sequence of this
      fragment was determined and found to contain one partial and four complete open
      reading frames. These were designated cpsA, cpsB, cpsC, cpsD and cpsE and encoded
      proteins of > 130, 243, 230, 246 and 455 amino acids, respectively, that showed
      homology with the genes of the cps cluster, involved in polysaccharide
      biosynthesis, in Streptococcus pneumoniae Type 19F. The cpsA gene is predicted to
      encode a transcriptional regulator, while cpsC and cpsD are predicted to encode
      proteins involved in polysaccharide polymerization and export. The cpsE gene is
      likely to encode the phosphate-prenyl glycosyl-1-phosphate transferase catalyzing
      the first step in polysaccharide biosynthesis in S. thermophilus. Southern blot
      analysis revealed that cpsE is found only in polysaccharide producing strains of
      S. thermophilus.

PMID- 8996083
TI  - Cosmid-derived transcripts and sequence tags mapped to three subregions of human
      chromosome 22.
AB  - Fifty cosmids from the ICRF, London, and Lawrence Livermore Laboratory,
      California, human chromosome 22 cosmid libraries were isolated, regionally
      assigned and tested for their ability to detect repeats or single copy sequences.
      The search resulted in nine cosmids containing repetitive motifs from the
      pericentric region of chromosome 22. An additional 19 cosmids, that detected
      single copy sequences in the long arm of chromosome 22q: 7 in the region 22q11.2
      q13.1 and 12 in 22q13.1-qter, were mapped more precisely by fluorescence in situ
      hybridization. Three out of these 19 recombinants displayed restriction fragments
      containing (CA)n repeats, were subcloned and sequenced. One cosmid, representing
      a region coding for an ubiquitous 300-bp transcript, is localized 600 kb from
      PDGFB, and four cosmids contained sequences surrounding the ARSA gene at 22q13.3.
      Presently, long range physical maps, that may be useful for analysing structural
      alterations of chromosome 22q13, are being constructed from these additional,
      regionally assigned markers from chromosome 22q13 employing both existing cosmid
      and new bacterial artificial chromosome (BAC) libraries.

PMID- 8996084
TI  - Cloning and sequencing of the gene encoding the Cu,Zn-superoxide dismutase of
      Haemophilus ducreyi.
AB  - The sodC gene of Haemophilus ducreyi was cloned and sequenced. The deduced amino
      acid sequence of this protein exhibited 71.6% identity and 81.8% similarity to
      the H. influenzae and H. parainfluenzae copper (Cu), zinc (Zn)-superoxide
      dismutase (SOD) enzymes. This gene was localized to a 2.2-kb H. ducreyi
      chromosomal DNA insert in plasmid pHdSOD. SOD activity was expressed in cell-free
      extracts of Escherichia coli containing the recombinant plasmid pHdSOD and was
      localized to the periplasmic space. The Cu,Zn-SOD produced by the H. ducreyi sodC
      gene did not complement the aerobic growth defect of an E. coli SOD-deficient
      mutant.

PMID- 8996085
TI  - Integration of the SV40 promoter/enhancer sequences in an anchorage-independent
      clonal subline of SV40-infected human keratinocytes.
AB  - Long-term cultures of SV40-infected human keratinocytes contain integrated, but
      structurally altered copies of the viral sequences. The presence of these
      sequences is required for expression of properties associated with the
      transformed phenotype including immortalization. The integrated viral sequences
      in an anchorage-independent line of viral-transformed human keratinocytes have
      been found to be contained on two BamHI fragments of about 6.9 and 5.2 kb. In the
      larger fragment the viral sequences were present as two tandemly repeated
      subgenomic fragments containing the viral origin/promoter region with nucleotide
      alterations that affect enhancer function, the origin of replication and T
      antigen binding site 1. The viral early gene promoter in one integrant gave rise
      to an unspliced fusion transcript comprised of a short portion of the viral early
      gene leader sequence and the flanking human sequences. The smaller fragment
      consisted of full-length SV40 containing a nine-nucleotide insertion in the C
      terminal portion of the SV40 T antigen, a region involved in the regulation of
      viral host range.

PMID- 8996086
TI  - Cloning and characterization of a Dictyostelium discoideum cDNA encoding a
      protein related to the medium chain subunit of clathrin-associated adaptor
      complexes.
AB  - We describe the cloning and characterization of a cDNA, DdApm1, encoding a
      putative medium chain subunit of a clathrin-associated protein (adaptor or
      assembly protein [AP]) complex in Dictyostelium discoideum. The DdApm1 clone is
      predicted to encode a polypeptide of 439 amino acids (aa) with a molecular mass
      of 49.9 kDa. The predicted translation product (DdApm1p) shares at least 51.7%
      identity and 76.3% similarity with the medium chain subunits of plasma membrane
      (mb)-associated clathrin AP complexes from rat and Caenorhabditis elegans. The
      deduced aa sequence also demonstrates significant but lesser homology to a number
      of medium chain subunits of Golgi-associated clathrin AP complexes. Since DdApm1p
      demonstrates significantly greater homology to plasma mb-associated clathrin AP
      complex medium chains than to their Golgi-associated counterparts, we suggest
      that DdApm1p may be a medium chain subunit of an AP complex involved in clathrin
      function at the plasma mb of D. discoideum. Southern blot analysis indicated that
      DdApm1 gene defines a single copy gene in the D. discoideum genome. Northern blot
      analysis of RNA purified at different times during growth and development
      demonstrated that the DdApm1 gene is expressed at relatively constant levels
      throughout the life cycle of the organism. DdApm1 is the first reported full
      length cDNA encoding a subunit of an AP complex in D. discoideum, and thus
      provides the first evidence for the existence of AP complexes in this organism.

PMID- 8996088
TI  - Molecular characterization and organization of porin from Rhodobacter capsulatus
      strain 37B4.
AB  - The primary and atomic structures of the porin protein from Rhodobacter (Rb.)
      capsulatus strain 37b4 were determined several years ago by peptide sequencing
      and X-ray crystallography. In this work the gene encoding this porin (named
      porCa) was cloned and sequenced. The porin open reading frame encodes 320 amino
      acids-a mature protein of 300 residues (molecular mass 31 552 kDa) and a
      presequence of 20 amino acids. Our deduced amino-acid sequence was directly
      confirmed by purifying the porin protein from the same bacterial strain and
      sequencing the amino terminus as well as several peptides derived from trypsin
      digestion. However, comparison of this deduced amino-acid sequence with the
      published primary structure of this porin, nominally from the same strain (but
      cultivated for ca. 30 years in a different laboratory) reveals seven differences
      in the amino-acid sequence at the following positions in the mature protein
      (published/present): 59 (Gly/Ala), 123 (Tyr/Asn), 135 Ser/Thr), 189 (Ile/Val),
      196 (Asn/His), 231 (Ala/Thr) and 238 (Ser/deleted). Surprisingly, analysis of the
      positioning of these mutations revealed that they are located exclusively on
      transmembrane strands, with two of them deeply buried within the structure. These
      mutations may in fact have only marginal influence on porin structure and
      function. Northern blot analysis revealed that porCa encodes an RNA transcript of
      1070 nucleotides. No differential response in the abundance or size of this mRNA
      was seen upon growth under phototrophic/anaerobic vs. chemotrophic/aerobic
      conditions, under high or low osmotic pressure. Primer extension experiments
      revealed a transcription start site 73 bases upstream from the ATG translation
      start, juxtaposed to the identified putative promoter region. Fusion of lacZ with
      this putative promoter region (using a 288-bp upstream region) revealed similar
      promoter activity in beta-galactosidase assays under both physiological
      conditions tested, again suggesting that this gene is constitutively expressed.
      The molecular genetic characterization described in this work opens the way for
      structure-function studies by site-directed mutagenesis.

PMID- 8996087
TI  - Genomic targeting with an MBP-Cre fusion protein.
AB  - The Cre recombinase of bacteriophage P1 catalyses site-specific recombination
      between lox-recombination target sites both in prokaryotic and eukaryotic cells
      and has thus become a popular tool in genetic research. Stable, Cre-mediated
      integration of DNA sequences at pre-existing lox sites in the eukaryotic genome
      is facilitated when a Cre recombinase protein rather than a cre-expression
      plasmid is used to direct site-specific recombination (Baubonis and Sauer (1993)
      Nucleic Acids Res., 21, 2025-2029). We bacterially produced a Cre recombinase
      containing a nuclear localisation signal as a fusion protein with the E. coli
      maltose binding protein (MBP) and purified the protein by one step affinity
      chromatography. Subsequent cleavage with the protease factor Xa releases the Cre
      recombinase including the nuclear localisation signal from the maltose binding
      protein. Surprisingly, we found that the recombination activity of the uncleaved
      MBP-Cre fusion protein is virtually identical to that of the native Cre
      recombinase. This suggests that the MBP portion of the fusion protein behaves as
      a separate protein domain which does not interfere with Cre activity and can thus
      be used as an independent molecular tag. Additionally, the fusion protein is very
      resistant to proteolytic degradation and active over a wide range of
      temperatures. It efficiently catalyses excision and integration reactions in
      vitro and in eukaryotic cells. Finally, we could show that, by using MBP-Cre, it
      is possible to concomitantly excise a lox-flanked DNA sequence from a plasmid and
      integrate it into a pre-existing lox site in the genome in one transfection
      experiment. Vector backbone sequences which might have undesirable effects can
      thereby be excluded. The MBP-Cre fusion protein described here will be a useful
      tool not only for the catalysis of Cre-mediated recombination reactions in vitro
      and in vivo but also for the analysis of the mechanism of site-specific
      recombination.

PMID- 8996089
TI  - Characterization of a tumor-associated gene, a member of a novel family of genes
      encoding membrane glycoproteins.
AB  - To isolate genes involved in tumor formation and in embryogenesis, a subtracted
      cDNA library was constructed from a c-myc-induced mouse brain tumor. A gene
      isolated in this screen, named TMP (tumor-associated membrane protein), codes for
      a putative glycoprotein with four transmembrane domains. The TMP gene was found
      to be highly expressed in brain tumor cells but not in normal brain. It is also
      expressed at high levels in undifferentiated embryonic stem cells, but markedly
      down-regulated in these cells after their differentiation into embryoid bodies.
      The TMP amino acid sequence bears high homology to the growth arrest specific
      protein PMP22/GAS-3, which is involved in several human peripheral neuropathies.
      The expression patterns of the TMP and PMP22 genes in NIH-3T3 fibroblasts were
      compared at different proliferation states. The results suggest an inverse
      pattern of expression for the two homologs, TMP expression being high during cell
      proliferation and PMP22 expression being high during growth arrest. To further
      characterize the TMP gene we have isolated its human homolog and examined its
      expression in embryonic and adult tissues. In our search for human sequences
      homologous to TMP and PMP22, we identified two new genes which we have named XMP
      and YMP. Thus, we present a novel family of membrane glycoproteins, one member of
      which is closely associated with proliferation and another with growth arrest.

PMID- 8996090
TI  - Conservation of function and expression of unc-119 from two Caenorhabditis
      species despite divergence of non-coding DNA.
AB  - The Caenorhabditis briggsae homologue of the Caenorhabditis elegans neuronal gene
      unc-119 has been cloned by low-stringency hybridization. Genomic clones
      containing the C. briggsae gene are able to completely rescue the unc-119
      phenotype in transgenic C. elegans mutants. The open reading frame (ORF) of the
      predicted C. briggsae cDNA is 90% identical to that of C. elegans. Although the
      splice donor and acceptor sites are conserved, the untranslated regions, and the
      introns, differ greatly. For this gene, the average intron size in C. elegans is
      over 600 base pairs (bp); in C. briggsae it is only 113 bp. Their upstream
      control regions share limited sequence similarities; however, reporter gene
      fusions of the two species show strongly similar expression in C. elegans. These
      results are consistent with the maintenance not only of the function of the unc
      119 gene but also the transcriptional control of the gene through tens of
      millions of years of evolution.

PMID- 8996091
TI  - Cloning and nucleotide sequence analysis of the Streptococcus mutans membrane
      bound, proton-translocating ATPase operon.
AB  - The function of the membrane-bound ATPase in S. mutans is to regulate cytoplasmic
      pH values for the purpose of maintaining delta pH. Previous studies have shown
      that as part of its acid-adaptive ability, S. mutans is able to increase H(+)
      ATPase levels in response to acidification. As part of the study of ATPase
      regulation in S. mutans, we have cloned the ATPase operon and determined its
      genetic organization. The structural genes from S. mutans were found to be in the
      order: c, a, b, delta, alpha, gamma, beta, and epsilon; where c and a were
      reversed from the more typical bacterial organization. The operon contained no I
      gene homologue but was preceded by a 239-bp intergenic space. Deduced aa
      sequences from open reading frames indicated that genes encoding homologues of
      glycogen phosphorylase and nonphosphorylating, NADP-dependent glyceraldehyde-3
      phosphate dehydrogenase flank the H(+)-ATPase operon, 5' and 3' respectively.
      Sequence analysis indicated the presence of three inverted-repeat nt sequences in
      the glgP-uncE intergenic space. Primer extension analysis of mRNAs prepared from
      batch-grown or steady-state cultures demonstrated that the transcriptional start
      site did not change as a function of culture pH value. The data suggest that
      potential stem-and-loop structures in the promoter region of the operon do not
      function to alter the starting position of ATPase-specific mRNA transcription.

PMID- 8996092
TI  - Phenobarbital-dependent protein binding to Barbie box-like sequences in the
      coding region of cytochrome P450BM-3 gene from Bacillus megaterium.
AB  - Phenobarbital-dependent protein binding was shown to occur to DNA fragments from
      the coding region of the cytochrome P450BM-3 gene from Bacillus megaterium.
      Incubation of the DNA fragments from the coding region of the gene with total
      cell extract from Bacillus megaterium revealed two DNA regions with protein
      binding capacity: +237/+318 and +319/+425 considering 'O' as the start of
      cytochrome P450BM-3 translation. DNaseI footprint analysis of the fragment
      +319/+425 with the total cell extract showed that some protein(s) protected DNA
      stretches from the position +373 up to the position +389 on the transcribed
      strand and from the position +378 up to the position +398 on the non-transcribed
      strand. DNaseI footprint analysis of the fragment +237/+318 revealed the
      protection in the region +262/+277 on the non-transcribed strand. Three regions
      protected by cell extract protein(s) from DNaseI hydrolysis (+262/+277, +373/+389
      and +378/+398) appeared to be strongly homologous to the Barbie box sequence.
      Barbie-box-like sequences were found in the majority of regulatory regions of
      phenobarbital-inducible genes whose regulatory sequences had been reported (Fulco
      et al., 1994). Our results suggest that a functional role of Barbie box sequence
      takes place not only in regulatory but also in the coding region of the gene. In
      line with that hypothesis we analyzed all cytochrome P450 genes in respect to the
      presence of Barbie box-like sequences in their coding parts. At least one
      cytochrome P450 gene (CYP6A1, phenobarbital-inducible gene from Musca domestica)
      was shown to contain Barbie box sequence in the coding part of the gene.

PMID- 8996094
TI  - A novel leaf-specific myb-related protein with a single binding repeat.
AB  - A novel myb-like gene (AtmybL2) was isolated from an Arabidopsis thaliana cDNA
      library. The single copy gene was localised on chromosome I. A gene specific
      transcript is preferentially found in leaves. The predicted gene product consists
      of a conservative N-terminal myb-domain known to be involved in DNA-binding and a
      unique proline-rich C-terminal part. Remarkably, the myb-domain includes only one
      of the typical two or three tryptophan repeats found in other myb-like proteins.

PMID- 8996093
TI  - A Drosophila gene regulated by rough and glass shows similarity to ena and VASP.
AB  - rough (ro) encodes a homeobox transcription factor required for proper
      specification of photoreceptor cells R2 and R5 in Drosophila eye development. To
      identify the transcriptional targets through which ro acts to specify the R2/R5
      neuronal sub-type, we screened enhancer trap lines expressed in developing
      photoreceptors for those whose expression patterns were altered when ro function
      was inactivated. In this way we identified two potential ro targets, which are
      also targets of the zinc finger transcription factor glass (gl). We also
      identified an enhancer trap line that exhibits altered morphogenetic furrow
      expression in a ro mutant background. Finally, we have molecularly characterized
      an enhancer trap line, AE33, that was identified in earlier screens as a target
      of both ro and gl (freeman et al., 1992; Treisman and Rubin, 1996). The
      transcript interrupted by AE33 shares similarity with the mammalian vasodilator
      stimulated phosphoprotein (VASP), a substrate for cAMP- and cGMP-dependent
      protein kinases that is associated with actin filaments, focal adhesions, and
      dynamic membrane regions (Haffner et al., 1995) with enabled (ena), a substrate
      of the Drosophila Abl tyrosine kinase (Gertler et al. 1995) and with two human
      Expressed Sequence Tags (ESTs).

PMID- 8996095
TI  - Cloning, sequencing and expression of an Eikenella corrodens gene encoding a
      component protein of the lectin-like adhesin complex.
AB  - A lectin-like substance (LS), that was isolated from Eikenella corrodens (Ec)
      1073, migrated as proteins of about 300 and 45 kDa upon sodium dodecyl sulfate
      polyacrylamide gel electrophoresis under reducing conditions. In this study, we
      cloned the gene encoding the 45-kDa protein and predicted its structure and
      function. Based on the N-terminal 23-amino acid (aa) sequence of this protein, we
      cloned the region for its N-terminus. We cloned the entire gene by means of gene
      walking using polymerase chain reaction and Southern hybridization. The
      nucleotide sequences of cloned fragments revealed an open reading frame encoding
      a polypeptide of 330 aa (M(r), 35748). This ORF displayed high homology to those
      of porins of Neisseria species. Using the T7-expression system, the 45-kDa
      protein was produced in E. coli. Our results suggested that the 45-kDa protein of
      Ec 1073 is a component of the EcLS complex, and that it is the major outer
      membrane protein.

PMID- 8996096
TI  - Molecular cloning and mRNA tissue distribution of a novel matrix
      metalloproteinase isolated from porcine enamel organ.
AB  - A cDNA encoding a novel matrix metalloproteinase (MMP) was isolated from a
      porcine enamel organ-specific cDNA library. Multiple tissue northern blot
      analysis revealed the presence of two mRNA transcripts which were expressed only
      in the enamel organ. The transcripts were 1968 bp or 3420 bp in length and
      resulted from the utilization of alternative polyadenylation sites. The open
      reading frame of the cloned mRNA encodes a protein composed of 483 amino acids.
      The MMP has a predicted molecular mass of 54.1 kDa, which is similar to that of
      the stromelysins or collagenases, although it is not a member of either of these
      two classes of MMPs. A motif analysis revealed that the cloned MMP does not
      contain a consensus hemopexin-like domain because it lacks a critical tryptophan
      and proline residue at the appropriate positions. Since the cloned MMP is a new
      member of the MMP gene family and its expression appears limited to the enamel
      organ, we have named it enamelysin.

PMID- 8996097
TI  - Construction of D29 shuttle phasmids and luciferase reporter phages for detection
      of mycobacteria.
AB  - Diseases caused by Mycobacterium tuberculosis, M. leprae and M. avium, cause
      significant morbidity and mortality worldwide. Effective treatments require that
      the organisms be speciated and that drug susceptibilities for the causative
      organisms be characterized. Reporter phage technology has been developed as a
      rapid and convenient method for identifying mycobacterial species and evaluating
      drug resistance. In this report we describe the construction of luciferase
      reporter phages from mycobacteriophage D29 DNA. Shuttle phasmids were first
      constructed with D29 in order to identify non-essential regions of the D29
      genomes and to introduce unique cloning sites within that region. Using this
      approach, we observed that all of the D29 shuttle phasmids had the cosmid vector
      localized to one area of the phage genome near one cohesive end. These shuttle
      phasmids had been constructed with a cosmid that could be readily excised from
      the D29 genome with different sets of restriction enzymes. Luciferase reporter
      phages were made by substituting the luciferase cassette for the cosmid vector.
      Recombinant phages with the luciferase cassette fall into two groups. One group
      produced light and had the expression cassette oriented with the promoter
      directing transcription away from the cohesive end. In contrast, the other group
      had the expression cassette in the opposite orientation and failed to produce
      light during lytic infection, but did produce light in L5 lysogens which are
      known to repress D29 promoters. These results suggest that a phage promoter of
      the D29 phage can occlude the expression of a promoter introduced into this
      region. D29 luciferase reporter phages are capable of detecting low numbers of L5
      lysogens like L5 luciferase phages. However, unlike L5 luciferase phages, D29
      luciferase phages can readily infect M. tuberculosis and M. bovis BCG,
      demonstrating that these phages can be used to evaluate drug susceptibilities of
      many types of mycobacteria.

PMID- 8996098
TI  - Inducible retroviral vectors regulated by lac repressor in mammalian cells.
AB  - We have developed lac repressor-regulated retroviral expression vectors that are
      induced by beta-galactosides upon stable transduction in mammalian cells. These
      vectors, derived from a Moloney-virus-based vector LNCX, contain an internal Rous
      sarcoma virus (RSV) or cytomegalovirus (CMV) promoter, coupled with 2 to 4 lac
      operator sequences and placed in anti orientation relative to the retroviral long
      terminal repeat (LTR). Three different vectors were tested in stably infected
      mass populations of mouse and human cells expressing the lac repressor, in
      parallel with the constitutively expressed LNCX vector. The highest expression
      levels from these vectors ranged from 1-4% to 25-33% of the LNCX level, and the
      induction by beta-galactosides ranged from 6-11-fold to 29-54-fold. These vectors
      should be suitable for studies requiring efficient gene transfer and regulated
      expression in mass populations of stably transduced mammalian cells.

PMID- 8996099
TI  - Minimal functional system required for expression of erythromycin resistance by
      msrA in Staphylococcus aureus RN4220.
AB  - Previous studies have suggested that inducible erythromycin (Er) resistance in
      staphylococci mediated by the plasmid-borne ABC-transporter msrA is dependent on
      additional unidentified chromosomally encoded transmembrane (TM) domains. The
      requirement for two S. aureus candidate sequences, stpC and smpC, highly similar
      to sequences adjacent to msrA on the original S. epidermidis plasmid was
      investigated. Deletion of the sequences by allelic replacement was accomplished
      by electroporation of S. aureus RN4220 with a nonreplicating suicide vector. S.
      aureus strains carrying a delta(stpC-smpC) mutation showed an identical ErR
      phenotype to those arising from single crossover events and unmutated RN4220
      containing msrA. This proves that neither stpC nor smpC is required for ErR. To
      further define the minimal functional unit required for MSR, the control region
      within the leader sequence of msrA was deleted. This resulted in constitutive
      resistance to Er and type B streptogramins (Sg), proving that SgR does not
      require the presence of Er. Deletion constructs containing the N- or C-terminal
      ABC regions of MsrA did not confer ErR in RN4220 singly or in combination.

PMID- 8996100
TI  - A new Bacillus subtilis gene with homology to Escherichia coli prc.
AB  - We report the cloning of a 2-kb PstI-BamHI fragment of Bacillus subtilis DNA
      carrying an open reading frame of 1398 bp, herein designated orfRM1. This orf was
      shown to be transcribed only during vegetative growth from a putative sigma A
      specific promoter. The deduced amino acid sequence predicted a polypeptide of 51
      kDa (466 aa), which shows significant percentage of identity with the Escherichia
      coli Prc protein. However no Prc-like phenotypes were observed in a B. subtilis
      orfRM1 deletion-insertion mutant.

PMID- 8996101
TI  - Positive-negative KG cassettes for construction of multi-gene deletions using a
      single drug marker.
AB  - Positive-negative KG cassettes were developed in order to create a number of
      independent deletion mutations on the bacterial chromosome using a single drug
      marker. These cassettes consist of a kanamycin-resistant (KmR) gene for positive
      screening and a galactokinase gene (galK) for negative screening. Both genes are
      in an operon driven by the native KmR promoter and are flanked by identical
      fragments of yeast chromosomal DNA approximately one kb in size. An internal
      region of a cloned target gene of a bacterium is replaced with a cassette, which
      is then transformed into the bacterium. The intact gene on the chromosome is
      replaced with the mutated gene by homologous recombination. From the KmR cells
      thus obtained, those cells which lose both KmR and galK genes by homologous
      recombination between the identical yeast DNA fragments are subsequently screened
      on plates containing 2-deoxygalactose, a non-metabolizable analogue of galactose.
      This method was applied to isolate a triple-deletion mutant of pkn3, pkn1, and
      pkn11 from Myxococcus xanthus.

PMID- 8996102
TI  - Isolation and molecular characterisation of the POL3 gene from Candida albicans.
AB  - In Saccharomyces cerevisiae, the CDC2 gene encodes the large subunit of DNA
      polymerase III, the analogue of mammalian DNA polymerase delta. We have isolated
      DNA fragments from a library of Candida albicans genomic DNA in the vector pRS316
      that rescue temperature sensitive cdc2 mutations in S. cerevisiae. These
      fragments contain an ORF coding for a protein of 1038 aa with a predicted
      molecular mass of 118.8 kDa. The predicted protein shows homology to a number of
      eukaryotic DNA polymerases, with 62% identity over its length to the S.
      cerevisiae Cdc2 protein. It also contains a number of motifs which are
      characteristic of DNA polymerases in general and viral polymerases in particular,
      as well as the conserved motif which interacts with proliferating cell nuclear
      antigen. These results indicate that this gene is C. albicans POL3. Analysis of
      the expression of C. albicans POL3 revealed that the transcript is present
      throughout the mitotic cell cycle, which contrasts with the expression of S.
      cerevisiae CDC2.

PMID- 8996103
TI  - Characterisation of genes involved in biosynthesis of coronafacic acid, the
      polyketide component of the phytotoxin coronatine.
AB  - Coronafacic acid (CFA) is the polyketide component of coronatine (COR), a
      phytotoxin produced by the plant pathogen, Pseudomonas syringae. In the present
      study we have determined the nucleotide sequence of a 3.92-kb DNA fragment
      involved in CFA biosynthesis. Analysis of the sequence revealed four complete
      open reading frames (ORFs) designated cfa1 to cfa4 and one incomplete ORF (cfa5),
      all transcribed in the same direction. The predicted translation products of
      cfa1, cfa2 and cfa3 showed relatedness to acyl carrier proteins, fatty acid
      dehydrases and beta-ketoacylsynthases, respectively, which are required for
      polyketide synthesis. cfa1 was subcloned, its sequence was confirmed, and it was
      overexpressed in E. coli to yield a peptide with an apparent molecular mass of 6
      kDa.

PMID- 8996104
TI  - Plasmid vectors for gram-positive bacteria switching from high to low copy
      number.
AB  - A set of vectors for Gram-positive bacteria was constructed with a new feature
      which enables the switching down of their copy number per cell. These vectors
      carry the replication region of pAM beta 1, containing a gene essential for
      replication, repE, and its regulator, copF. The latter gene was inactivated by
      inserting a linker into its unique KpnI site. Since copF downregulates the
      expression of repE, its inactivation leads to an increase in the plasmid copy
      number per cell. The original low copy state can be restored by removal of the
      linker via KpnI cleavage and ligation. The new replicon was used to build (i)
      vectors for studying gene regulation by transcriptional or translational fusion
      with the bacterial luciferase gene, (ii) vectors for gene expression, and (iii)
      cassettes of the replicon with different multiple cloning sites, which would
      facilitate construction of vectors for novel purposes.

PMID- 8996105
TI  - Cloning of a cDNA encoding DNA topoisomerase I in Daucus carota and expression
      analysis in relation to cell proliferation.
AB  - DNA topoisomerase I is an enzyme involved in several processes related to DNA
      metabolism. Despite the physiological importance, the regulation of top1 gene
      expression has not yet been investigated in plants. In order to monitor the
      possible correlation between levels of top1 transcripts and the proliferative
      state of the cell, two partially overlapping cDNAs encoding DNA topoisomerase I
      from Daucus carota have been isolated from a poly(A)(+)-primed library, using an
      Arabidopsis thaliana probe, and from a cDNA library spanning the 5' region of the
      top1 transcript, which was constructed using an antisense specific
      oligonucleotide. The top1 nucleotide sequence encoded an open reading frame of
      2370 bp, predicting a protein of 90 kDa. The deduced amino acid sequence showed a
      similarity of 51% with A. thaliana, 41% with S. cerevisiae, 40% with S. pombe and
      31% with H. sapiens, respectively. Southern blot analysis, performed under
      moderate stringency conditions, showed the presence of a single-copy gene.
      Evaluation of the top1 mRNA steady-state level revealed, besides a constitutive
      expression in vegetative carrot tissues, an induced expression related to cell
      proliferation.

PMID- 8996106
TI  - Two alternative promoters drive the expression of the cytoplasmic actin A4 gene
      of Bombyx mori.
AB  - By screening cDNA and genomic libraries, we have cloned A4, the fourth and last
      actin gene of Bombyx mori, which encodes a typical cytoskeleton actin and is
      expressed in all larval tissues. A4 is closely related to A3, another cytoplasmic
      actin gene of the silkworm, in its encoded amino-acid sequence, and the location
      as well as the sequence of a single intron. Both A3 and A4 have possibly arisen
      from the recent duplication of an intron-containing ancestral gene. The two genes
      display different organization of their 5' untranslated and flanking sequences.
      In contrast to A3, which harbours a single promoter, A4 exhibits two leader exons
      transcribed by the use of alternative promoters. A3 and A4 actins differ only by
      two amino acids at positions known to vary among cytoplasmic actins of other
      species, and are likely to be functionally equivalent. We speculate that
      transcriptional constraints are actually the target of a selective pressure that
      maintains two distinct cytoplasmic actin genes in insects, as well as in other
      animals.

PMID- 8996107
TI  - The Bradyrhizobium japonicum coxWXYZ gene cluster encodes a bb3-type ubiquinol
      oxidase.
AB  - Bradyrhizobium japonicum, a symbiotic nitrogen-fixing bacterium, has a complex
      respiratory electron-transport chain, capable of functioning throughout a wide
      range of oxygen tensions. It does so by synthesizing a number of terminal
      oxidases, each appropriate for different environmental conditions. We have
      previously described the cloning of the large catalytic subunit, coxX, from one
      of the terminal oxidases from B. japonicum [Surpin, M.A., Moshiri, F., Murphy,
      A.M. and Maier, R.J. (1994) Genetic evidence for a fourth terminal oxidase from
      Bradyrhizobium japonicum. Gene 143, 73-77]. In this work, we describe the
      remaining subunits of this terminal oxidase complex, which is encoded by the
      coxWXYZ operon. The polypeptide encoded by coxW does not contain any amino acid
      residues that are known to bind the CuA atom of cytochrome c terminal oxidases,
      but contains residues thought to be involved in ubiquinol binding. Terminal
      oxidase cyanide inhibition titration pattern comparisons of the wild type with a
      coxWXYZ insertion mutant indicated the new oxidase is expressed microaerobically.
      However analysis of hemes extracted from microaerobically incubated cells
      revealed the absence of heme O in this strain (from both the wild type and the
      mutant) of B. japonicum. Therefore, coxWXYZ most likely encodes a
      microaerobically-expressed bb3-type ubiquinol oxidase.

PMID- 8996108
TI  - Identification of a new iron regulated locus of Salmonella typhi.
AB  - In order to identify genes belonging to the Fur regulon of Salmonella typhi which
      are absent from Escherichia coli K-12, a plasmid gene bank consisting of 4000
      independent clones was screened for Fur regulated promoters using the Fur
      titration assay (FURTA). DNA probes generated from FURTA positive plasmids were
      then used for hybridization with chromosomal DNA from S. typhi, Salmonella
      typhimurium and E. coli. Using these techniques we identified an iron regulated
      locus present in S. typhi and S. typhimurium but not in E. coli. Further cloning
      and nucleotide sequence analysis identified two open reading frames, termed
      iroBC, organized in a typical operon structure. The genes iroBC were located at 4
      and 57 centisomes on the physical maps of Salmonella typhi and S. typhimurium,
      respectively. This region of the S. typhimurium chromosome contains a large DNA
      loop which is absent from the corresponding area of the E. coli chromosome.
      Finally, we developed a new method for generation of single copy transcriptional
      fusions. A suicide vector was constructed, which allows for the generation of
      chromosomal fusions to the promoterless E. coli lacZYA genes. By integration of
      this construct at the iro locus we could establish iron responsive expression of
      iroBC.

PMID- 8996110
TI  - Characterization of Campylobacter upsaliensis fur and its localization in a
      highly conserved region of the Campylobacter genome.
AB  - Despite increasing recognition of the importance of Campylobacter upsaliensis in
      human disease little is known about either the virulence properties or genetics
      of this enteric pathogen. The complete coding sequence of a C. upsaliensis gene
      has yet to be published. We have cloned and sequenced the complete iron-uptake
      regulatory (fur) gene from the type strain of this species. The C. upsaliensis
      fur homolog was isolated from a genomic library of C. upsaliensis ATCC 43954
      constructed in phage lambdaGEM-11. The open reading frame identified encodes a
      polypeptide consisting of 156 amino acids. The 5'-flanking region of the C.
      upsaliensis fur gene contains 3 putative Fur-binding sequences and two catabolite
      activator-binding sequences indicating the potential for autogenous and cAMP
      mediated regulation, respectively. Primer extension analysis identified a single
      transcription start site 262 nt upstream from the AUG initiation codon. Sequence
      analysis indicates that the Fur protein of C. upsaliensis is highly homologous
      (87% amino acid identity) to Campylobacter jejuni Fur. Furthermore, the
      arrangement of the lysS and glyA genes downstream of fur is precisely conserved
      in both C. upsaliensis ATCC 43954 and C. jejuni TGH9011. Using the polymerase
      chain reaction close linkage of fur with lysS and glyA was also observed among
      multiple isolates of C. upsaliensis, C. jejuni and C. coli suggesting a possible
      functional relevance for this conserved genetic arrangement in campylobacteria.

PMID- 8996109
TI  - Molecular cloning and expression of NlaIII restriction-modification system in E.
      coli.
AB  - The NlaIII restriction enzyme isolated from Neisseria lactamica recognizes the
      sequence 5'-CATG-3', cleaving after the G to generate a four base 3' overhang.
      The NlaIII methylase and a portion of the NlaIII endonuclease gene were cloned
      into E. coli by the methylase selection method, and the remaining portion of the
      NlaIII endonuclease gene was cloned by inverse PCR. The nucleotide sequence of
      the endonuclease gene and the methylase gene were determined. The NlaIII
      endonuclease gene is 693 bp, encoding a protein with predicted molecular weight
      of 26487. The NlaIII methylase gene was identical with that previously reported
      [Labbe, D., Joltke, H.J. and Lau, P.C. (1990) Cloning and characterization of two
      tandemly arranged DNA methyltransferse genes of Neisseria lactamica: an adenine
      specific M.NlaIII and a cytosine-type methylase. Mol. Gen. Genet. 224, 101-110].
      The endonuclease and methylase genes overlap by four bases and are transcribed in
      the same orientation. The endonuclease gene was cloned into an improved T7
      vector, and a high level of NlaIII endonuclease expression was achieved in E.
      coli.

PMID- 8996111
TI  - Detection and characterization of two novel hypervariable microsatellite repeat
      regions within intron 2 of the alpha-globin gene of the bivalve mollusc Anadara
      trapezia.
AB  - Synthetic oligonucleotide primers based on cDNA sequence were used to amplify the
      region spanning intron 2 of the alpha-globin gene of the bivalve mollusc Anadara
      trapezia. Amplification of this region from individual clams showed highly
      polymorphic patterns. The sequence of this intron was found to include a number
      of mono- [d(T)n and d(C)n], di- [d(CA)n and d(CT)n] and tetranucleotide d(CTGT)n
      repeats which were found to be polymorphic with respect to the types and numbers
      of repeats present. Two separate repeat-containing polymorphic regions were
      located near each end of this intron. The repeat at the 3' end consisted of an
      unusual example of a d(T)n polymorphism at the position of the polypyrimidine
      tract usually involved in intron splicing. Thirteen individual cloned intron 2
      sequences, derived by PCR amplification from pooled genomic DNA, were sequenced
      without finding two identical sequences. All of the sequenced clones contained
      microsatellite sequences.

PMID- 8996112
TI  - Production of a novel polyketide through the construction of a hybrid polyketide
      synthase.
AB  - The lactone rings of the polyketides platenolide and tylactone are synthesized by
      condensation of acetate-, proprionate-, and butyrate-derived precursors. A hybrid
      tylactone/platenolide synthase was constructed to determine if the choice of
      substrate is programmed by the polyketide synthase and to ascertain if a
      substrate different than that normally used in the first step of platenolide
      synthesis could be incorporated into the final polyketide. In this work, we
      report the successful incorporation of a propionate in place of the acetate
      normally used in the first step of platenolide synthesis. This result
      demonstrates that polyketide synthases choose a particular substrate at defined
      steps and provides strong evidence that substrate choice is programmed by the
      acyl transferase domain of a large, multifunctional polyketide synthase.

PMID- 8996113
TI  - Sequence, overproduction and purification of Vibrio proteolyticus ribosomal
      protein L18 for in vitro and in vivo studies.
AB  - A strategy suggested by comparative genomic studies was used to amplify the
      entire Vibrio proteolyticus (Vp) gene for ribosomal protein L18. Vp L18 and its
      flanking regions were sequenced and compared with the deduced amino acid (aa)
      sequences of other known L18 proteins. A 26-aa residue segment at the carboxy
      terminus contains many strongly conserved residues and may be critical for the
      L18 interaction with 5S rRNA. This approach should allow rapid characterization
      of L18 from large numbers of bacteria. Both Vp L18 and Escherichia coli (Ec) L18
      were overproduced and purified using a T7 expression vector which fuses an N
      terminal peptide segment (His-tag) containing 6 histidine residues to the
      recombinant protein. The purified fusion proteins, Vp His::L18 and Ec His::L18,
      were both found to bind to either the Vp 5S or Ec 5S rRNAs in vitro. Vp His::L18
      protein was also shown to incorporate into Ec ribosomes in vivo. This His-tag
      strategy likely will have general applicability for the study of ribosomal
      proteins in vitro and in vivo.

PMID- 8996114
TI  - Cloning and nucleotide sequence of a flagellin encoding genetic locus from
      Xenorhabdus nematophilus: phase variation leads to differential transcription of
      two flagellar genes (fliCD).
AB  - The insect-pathogenic bacterium Xenorhabdus undergoes spontaneous phase variation
      involving a large number of phenotypes. Our previous study indicated that phase I
      variants were motile, whereas phase II variants of X. nematophilus F1 were
      nonflagellated cells which did not synthesize flagellin [Givaudan A.,
      Baghdiguian, S., Lanois, A. and Boemare, N. (1995) Appl. Environ. Microbiol. 61,
      1408-1413]. In order to approach the study of the flagellar switching, a locus
      containing two ORFs from X. nematophilus F1 (phase I) was identified by using
      functional complementation of flagellin-negative E. coli. The sequence analysis
      revealed that the first ORF corresponds to the fliC gene coding for flagellin,
      and showed a high degree of homology between the N-terminal and C-terminal of
      Xenorhabdus FliC and flagellins from other bacteria. The second identified ORF in
      the opposite orientation encodes a homologue of the enterobacterial hook
      associated protein 2, FliD. Both Xenorhabdus fliCD genes were required for the
      entire restoration of E. coli motility. A sequence highly homologous to the sigma
      28 consensus promoter was identified upstream from the coding sequences from both
      genes. The structure of the fliC gene and its surrounding region was shown to be
      the same in both phase variants, but Northern blot analysis revealed that fliC
      and fliD were, respectively, not and weakly transcribed in phase II variants. In
      addition, complementation experiments showed that motility and flagellin
      synthesis of phase II cannot be recovered by placing in trans fliCD genes from
      phase I. These latter results suggest that a gene(s) higher in the
      transcriptional hierarchy of the flagellar regulon is switched off in Xenorhabdus
      phase II variants.

PMID- 8996115
TI  - Cloning and nucleotide sequencing of the protease gene of Vibrio vulnificus.
AB  - The gene (vvp) encoding a thermolabile protease of Vibrio vulnificus was cloned
      and sequenced. The transcription start point was also determined by primer
      extension. The product of this gene is very likely the secretory neutral
      metalloprotease that has been purified and characterized previously.

PMID- 8996116
TI  - A single vector cloning, mutagenesis and expression system.
AB  - We describe a multipurpose Escherichia coli vector, pOTSf1blue, that can be
      utilized for high efficiency subcloning, epitope-tagged protein overexpression,
      authentic protein overexpression and efficient mutagenesis.

PMID- 8996117
TI  - Economic analyses of new technologies: the case of stem-cell transplantation.

PMID- 8996119
TI  - Outpatient high-dose chemotherapy with autologous stem-cell rescue for
      hematologic and nonhematologic malignancies.
AB  - PURPOSE: A prospective study to determine the feasibility of high-dose
      chemotherapy (HDC) and autologous stem-cell rescue (ASCR) in the outpatient
      setting. METHODS: One hundred thirteen consecutive patients underwent 165 cycles
      of HDC/ASCR for a variety of malignancies. HDC regimens were disease-specific.
      Initially, patients were hospitalized for HDC, discharged on completion, and
      maintained as outpatients unless toxicities required rehospitalization (subtotal
      outpatient transplantation [STOT]). Once this was established as safe, a total
      outpatient transplant (TOT) program was developed in which patients received all
      of the HDC, as well as supportive care, as outpatients. Patients who declined the
      outpatient programs received the same HDC and supportive care as inpatients.
      RESULTS: In 140 of 165 (85%) HDC cycles, patients agreed to participate in one of
      the outpatient transplant programs. Five patients in the STOT program could not
      be discharged from the hospital because of toxicities that developed during HDC;
      thus, 135 patients were monitored the outpatient setting, 95 (70%) of whom were
      never readmitted. The mean +/- SEM total hospital length of stay (LOS), including
      all readmissions and excess days after chemotherapy, was 18.33 +/- 5.06 days for
      patients who refused the outpatient program, 8.22 +/- 5.76 days for patients in
      the STOT program, and 2.81 +/- 7.66 days for those in the TOT program (P < .001).
      One treatment-related death occurred in each treatment setting: day 120
      inpatient, day 17 STOT, and day 110 TOT. CONCLUSION: Outpatient management of
      HDC/ASCR is safe and acceptable for the vast majority of patients. The STOT
      program resulted in significant reduction in hospital LOS, while the TOT program
      appears equally safe and further reduces LOS. Hospitalization for HDC/ASCR is
      unnecessary in most patients.

PMID- 8996118
TI  - Economic analysis of a randomized clinical trial to compare filgrastim-mobilized
      peripheral-blood progenitor-cell transplantation and autologous bone marrow
      transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma.
AB  - PURPOSE: High-dose chemotherapy (HDC) with peripheral-blood progenitor cell
      (PBPC) and autologous bone marrow (ABM) transplant (T) has documented survival
      benefits for relapsed Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL).
      Treatment costs associated with HDC and its supportive care have restricted its
      use both on and off clinical trial. In a prospective randomized clinical trial,
      filgrastim-mobilized PBPCT resulted in faster recovery of bone marrow function,
      with less hospitalization and supportive care than ABMT. This study was
      undertaken to analyze the costs of the two strategies using prospectively
      collected data from a randomized clinical trial that compared filgrastim
      mobilized PBPCT versus ABMT. PATIENTS AND METHODS: Clinical results and resource
      utilization from a randomized clinical trial that compared filgrastim-mobilized
      PBPCT versus ABMT following carmustine, etoposide, cytarabine, and melphalan
      (BEAM) HDC for HD and NHL are presented. The trial was performed in six centers
      in Germany, the United Kingdom, and Belgium. Resource utilization data were used
      to project costs and Massay Cancer Center (MCC) in the United States incurred the
      cost of treating the cohort. Costs were projected to the United States, because
      the economic implications to United States centers are significant, costs of care
      vary markedly among countries but resource utilization on this trial did not, and
      a randomized trial is unlikely to be performed in the United States. RESULTS:
      Fifty-eight patients with relapsed HD or NHL underwent HDC with BEAM. The PBPCT
      and ABMT groups had similar short-term survival after BEAM. PBPCT patients had a
      shorter hospitalization (median, 17 v 23 days; P = .002), neutrophil recovery (11
      v 14 days; P = .005), platelet recovery to > or = 20 x 10(9)/L (16 v 23 days; P =
      .02), and days of platelet transfusions (6 v 10; P < .001). Estimated costs were
      $8,531 for ABM harvest and $5,760 for PBPC collection, including filgrastim
      mobilization. The total estimated average cost was $59,314 for each ABMT patient
      versus $45,792 for each PBPCT patient. Cost savings of $13,521 (23%) were due to
      shorter hospitalizations with less supportive care. CONCLUSION: PBPCT is as safe
      and more effective than ABMT for HD and NHL in the short term. PBPCT represents a
      significant cost savings due to lower autograft collection costs, shorter
      hospital stays, and less supportive care. The savings exceed the costs for
      filgrastim mobilization and PBPC collection. Actual savings will vary depending
      on local practice patterns, charges, and costs.

PMID- 8996120
TI  - Influence of age on the outcome of 500 autologous bone marrow transplant
      procedures for hematologic malignancies.
AB  - PURPOSE: To determine the effect of age on the outcome of autologous bone marrow
      transplantation (ABMT) and/or peripheral-blood progenitor-cell (PBPC)
      transplantation. PATIENTS AND METHODS: A retrospective analysis was performed on
      500 consecutive patients who ranged in age from 1 to 65 years (median, 40) with
      non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), multiple myeloma (MM), or
      acute nonlymphoblastic leukemia (AML) who underwent autologous hematopoietic-cell
      transplant procedures at Stanford University Medical Center. RESULTS: The
      actuarial 5-year event-free survival (EFS) rate was 44%, the relapse rate 47%,
      and the regimen-related mortality (RRM) rate 8.6%. Disease status at time of
      transplantation, categorized as either minimal or advanced disease, was the
      strongest predictive factor for EFS (relative risk (RR) for advanced-disease
      group, 1.8; P < .0003) and relapse rate (RR for advanced-disease group, 1.9; P <
      .0004). Patients with minimal or advanced disease had an EFS rate of 48% and 30%
      and relapse rates of 43% and 72%, respectively. The EFS rate of patients less
      than 50 years verus > or = 50 years of age was 46% versus 34% (P = .03). Cox
      regression analysis showed that age was predictive for EFS (RR for patients 50 to
      65 years, 1.4; P = .03). The actuarial RRM rate for these age groups was 7.4%
      versus 12.7% (P = .07), respectively. Multivariate analysis demonstrated that age
      (odds ratio [OR] for patients 50 to 65 years, 1.9; P < .05) and period of
      transplantation (OR for most recent years [1991 to 1995], 0.6; P = .06) were the
      most predictive factors for RRM. CONCLUSION: Although age greater than 50 years
      is associated with an inferior outcome following autologous hematopoietic-cell
      transplantation, it does not appear to be warranted to limit this potentially
      curative procedure based solely on age. The upper age limit of high-dose therapy
      with autologous progenitor-cell and/ or bone marrow support remains to be
      defined.

PMID- 8996121
TI  - Value of molecular monitoring during the treatment of chronic myeloid leukemia: a
      Cancer and Leukemia Group B study.
AB  - PURPOSE: Disappearance of the Philadelphia chromosome during treatment for
      chronic myeloid leukemia (CML) has become an important therapeutic end point. To
      determine the additional value of molecular monitoring during treatment for CML,
      we performed a prospective, sequential analysis using quantitative Southern blot
      monitoring of BCR gene rearrangements of blood and marrow samples from Cancer and
      Leukemia Group B (CALGB) study 8761. PATIENTS AND METHODS: Sixty-four previously
      untreated adults with chronic-phase CML who were enrolled onto CALGB 8761, a
      molecular-monitoring companion study to a treatment study for adults with chronic
      phase CML (CALGB 9013). Treatment consisted of repetitive cycles of interferon
      alfa and low-dose subcutaneous cytarabine. Blood and marrow Southern blot
      quantitation of BCR gene rearrangements was compared with marrow cytogenetic
      analysis before the initiation of treatment and of specified points during
      therapy. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was
      performed to detect residual disease in patients who achieved a complete response
      by Southern blot or cytogenetic analysis. RESULTS: Quantitative molecular
      monitoring by Southern blot analysis of blood samples was found to be equivalent
      to marrow monitoring at all time points. Twelve of 62 (19%) follow-up samples
      studied by Southern blot analysis had a complete loss of BCR gene rearrangement
      in matched marrow and blood specimens. Southern blot monitoring of blood samples
      was also found to be highly correlated to marrow cytogenetic evaluation at all
      points, although there were four discordant cases in which Southern blot analysis
      of blood showed no BCR gene rearrangement, yet demonstrated from 12% to 20%
      Philadelphia chromosome-positive metaphase cells in the marrow. RT-PCR analysis
      detected residual disease in five of six patients in whom no malignant cells were
      detected using Southern blot or cytogenetic analyses. CONCLUSION: Quantitative
      Southern blot analysis of blood samples may be substituted for bone marrow to
      monitor the response to therapy in CML and results in the need for fewer bone
      marrow examinations. To avoid overestimating the degree of response, marrow
      cytogenetic analysis should be performed when patients achieve a complete
      response by Southern blot monitoring. This approach provides a rational, cost
      effective strategy to monitor the effect of treatment of individual patients, as
      well as to analyze large clinical trials in CML.

PMID- 8996122
TI  - Major activity of cladribine in patients with de novo B-cell prolymphocytic
      leukemia.
AB  - PURPOSE: De novo B-cell prolymphocytic leukemia (B-PLL) is a distinct
      clinicopathologic entity usually characterized by marked lymphocytosis, massive
      splenomegaly, an aggressive course, and refractoriness to therapy. Cladribine (2
      chlorodeoxyadenosine [2-CdA]; Ortho Biotech, Raritan, NJ) is a newer purine
      analog with potent activity against indolent lymphoproliferative disorders.
      PATIENTS AND METHODS: We treated eight patients with cladribine 0.1 mg/kg/d for 7
      days by continuous infusion or 0.14 mg/kg/d over 2 hours for 5 days, every 28 to
      35 days, for a median of three courses (range, two to five). There were five men
      and three women, with a median age of 62 years and a median pretreatment duration
      of 6 months; four patients were previously untreated. RESULTS: All eight patients
      were assessable: five achieved a complete response with a median response
      duration of 14 months (range, 1+ to 55+), and three achieved a partial response
      with a median duration of 3 months (range, 1 to 3). Of four patients who achieved
      a complete response and in whom a peripheral-blood immunophenotypic analysis was
      performed, two had no circulating B-PLL cells and one had no residual disease on
      Southern blot analysis. Myelosuppression and infection were the major toxicities:
      three patients developed grade 3 or 4 myelosuppression, four had bacterial
      infections, and two had herpes zoster infections. CONCLUSION: In this small study
      of patients with de novo B-PLL, cladribine was an active agent that induced a
      high overall and complete response rate. These results require confirmation in
      larger numbers of B-PLL patients.

PMID- 8996123
TI  - Phase I clinical and laboratory evaluation of topotecan and cytarabine in
      patients with acute leukemia.
AB  - PURPOSE: To determine the maximal-tolerated dose (MTD) of topotecan with
      cytarabine in acute leukemia patients, and to evaluate leukemia cell apoptosis in
      these patients. PATIENTS AND METHODS: Fifty-three patients with acute leukemia
      not responsive to standard therapy were treated at eight dose levels of topotecan
      (2.5 mg/m2/d to 7.75 mg/m2/d). Topotecan was given as a 30-minute infusion daily
      with cytarabine 1 g/m2/d, both for 5 days. Using a flow-cytometric technique, the
      percent apoptotic cells in blood and bone marrow samples was determined, and the
      cell cycle distribution of the leukemic cells studied. RESULTS: Oropharyngeal
      mucositis was dose-limiting. The MTD of topotecan was 4.75 mg/m2/d for 5 days in
      high-risk patients and 7.0 mg/m2/d for 5 days in low-risk patients. The mean
      percent apoptotic cells in the peripheral blood reached a peak of 18.8%, a median
      of 48 hours following the first dose of topotecan. Patients with higher S-phase
      fractions, either before treatment or following cytarabine, were more likely to
      achieve bone marrow aplasia than those with lower S-phase fractions (P = .01 and
      P < .05, respectively). Clinical responses were seen in four of 39 patients with
      acute myelogenous leukemia (AML; of whom 32 had received prior high-dose
      cytarabine), three of six with acute lymphoblastic leukemia (ALL), and one of
      eight with chronic myelogenous leukemia in blast phase (CML-BP). CONCLUSION: The
      recommended phase II dose of topotecan with intermediate-dose cytarabine is 4.75
      mg/m2/d for high-risk patients and 7.0 mg/m2/d for low-risk patients. The
      percentage of cells in S phase was important in determining response to
      treatment.

PMID- 8996124
TI  - Case/control study of the role of splenectomy in chronic lymphocytic leukemia.
AB  - PURPOSE: This retrospective analysis was performed to evaluate critically the
      morbidity and mortality of splenectomy in patients with chronic lymphocytic
      leukemia and to determine the probability of hematologic response. Further, using
      a case/control format based on multivariate analysis-derived predictors of
      survival, we evaluated the influence of splenectomy on survival. PATIENTS AND
      METHODS: Between 1971 and 1993, 55 patients with chronic lymphocytic leukemia
      underwent splenectomy. They were compared with 55 fludarabine-treated patients
      who had been matched for age, serum albumin level, sex, hemoglobin level, Rai
      stage, number of prior therapies, and time from diagnosis. RESULTS: In the
      perioperative period, blood-product usage was modest, and common morbidities were
      limited to minor infections in 18% of the patients and pneumonia/atelectasis in
      25%. Perioperative mortality was 9%. Deaths were related to septic complications
      in all cases and associated with a preoperative performance status > or = 2 (P =
      .05). The only predictor identified for hemoglobin and neutrophil increments was
      spleen weight (P < .05). No factors predictive of platelet increment were
      identified. The early death rate (within 30 days) and overall survival of
      splenectomy and control patients were not significantly different (P > .2). Among
      Rai stage IV patients, those who were splenectomized displayed a strong trend for
      improved overall survival (P = .15 by log-rank test). The 2-year actuarial
      survival rate of Rai stage IV patients was 51% +/- 9% in the splenectomy group
      and 28% +/- 9% in the control group. CONCLUSION: Splenectomy can be performed
      with modest morbidity, mortality, and resource utilization in patients with
      advanced chronic lymphocytic leukemia and significant cytopenias. The procedure
      results in major hematologic benefits in most patients, with hemoglobin and
      neutrophil increments correlated with spleen weight. Overall, the survival of
      splenectomized patients is equivalent to control patients. Thrombocytopenic
      patients (< 100 x 10(9)/L) are most likely to obtain hematologic benefit, and
      potentially enjoy improved survival. These patients would be suitable for a
      randomized study to establish definitively the role of splenectomy in chronic
      lymphocytic leukemia.

PMID- 8996125
TI  - Anthracycline dose in childhood acute lymphoblastic leukemia: issues of early
      survival versus late cardiotoxicity.
AB  - PURPOSE: Late abnormalities of left ventricular (LV) performance occur in most
      survivors of childhood acute lymphoblastic leukemia (ALL) treated with moderate
      anthracycline doses. We studied the prevalence of late cardiotoxicity in patients
      treated with lower anthracycline doses and related this to survival. PATIENTS AND
      METHODS: Echocardiograms were performed in 50 normal children and 120 relapse
      free ALL survivors 6.2 +/- 2.0 years after the end of cumulative daunorubicin
      doses of 90 mg/m2 (n = 40), 180 mg/m2 (n = 40), or 270 mg/m2 (n = 40) on UKALL X
      pilot (1982 to 1984) or UKALL X (1985 to 1989) protocols. Age at treatment onset
      was 4.7 +/- 2.8 years. Cardiac abnormalities were reviewed in light of the UKALL
      X 5-year disease-free survival rates of 57% (95% confidence interval [CI], 51% to
      63%), 61% to 62% (95% CI, 56% to 68%), and 71% (95% CI, 66% to 76%) for the
      groups that received 90, 180, and 270 mg/m2 of daunorubicin, respectively.
      RESULTS: ALL survivors had reduced LV fractional shortening (FS) compared with
      normal (32.3% +/- 4.4% v 35.9% +/- 4.2%, P < .005), which was accounted for by
      increased LV end-systolic stress (49.4 +/- 13.5 v 42.2 +/- 9.1 g/cm2, P < .001),
      whereas LV contractility independent of loading conditions was normal for the
      group as a whole. Of 27 patients (23%) with cardiac abnormalities, 25 (21%) had
      increased end-systolic stress, whereas only two (2%) had reduced contractility.
      The proportion with cardiac abnormality was similar in the three dose groups.
      Anthracycline dose, age at treatment, sex, follow-up duration, growth hormone,
      pubertal status, hemoglobin level, and total WBC count at presentation were not
      predictive of increased LV end-systolic stress. CONCLUSION: There was a reduced
      incidence and severity of cardiac abnormalities with the lower anthracycline dose
      protocols (90 to 270 mg/m2) studied compared with previous reports in which
      subjects had received moderate anthracycline doses (approximately 300 to 550
      mg/m2). Cumulative anthracycline dose within the range 90 to 270 mg/m2 did not
      relate to cardiac abnormalities. This suggests that there may be no safe
      anthracycline dose to avoid late cardiotoxicity, but reinforces the use of the
      protocol that affords best survival within the dose range studied.

PMID- 8996126
TI  - Preservation of the bladder in patients with rhabdomyosarcoma.
AB  - PURPOSE: To review the pathologic findings from children with gross residual
      rhabdomyosarcoma (RMS) of the bladder and compare the treatment outcome of those
      who underwent cystectomy with those who did not. PATIENTS AND METHODS: Primary
      and follow-up records and pathology specimens for 28 patients with gross residual
      disease entered onto the intergroup Rhabdomyosarcoma Study (IRS) III were
      reviewed. These patients were assigned to receive 20 weeks of multiagent
      induction chemotherapy and 4 weeks of radiotherapy. Future therapy decisions were
      based on clinical and histologic evaluation at 20 weeks. RESULTS: All patients
      had a clinical and histologic response. Thirteen patients underwent cystectomy at
      intervals that ranged from 1.5 to 38 months after the start of therapy. All but
      one patient are alive and well without recurrence. Reasons for cystectomy
      included presumed evidence of tumor growth from imaging studies, findings at
      cystoscopy, or histologic interpretation of biopsies. In 12 of 14 specimens from
      15 patients who retained their bladder, no tumor cells were seen at first or
      second evaluation. In cystectomy specimens, tumor cellularity was markedly
      reduced and all tumor cells were in varying degrees of cellular maturation.
      Review of primary tumor specimens showed a greater degree of cellular maturation
      in patients with retained bladders than in those who underwent cystectomy.
      CONCLUSION: Bladder RMS is responsive to chemotherapy and radiotherapy. Twelve of
      26 patients showed complete loss of tumor cells after induction therapy.
      Cystectomy specimens showed diminished tumor cells with varying degrees of
      cellular maturation. It is hypothesized that these tumors may have shown further
      maturation and ultimate loss of matured cells with continuing therapy.

PMID- 8996128
TI  - MYCN oncogene amplification in neuroblastoma is associated with worse prognosis,
      except in stage 4s: the Italian experience with 295 children.
AB  - PURPOSE: To evaluate the prognostic role of MYCN oncogene amplification in
      children with neuroblastoma. PATIENTS AND METHODS: Of 694 children (age, 0 to 15
      years) with previously untreated neuroblastoma, 295 (42%) were evaluated at
      diagnosis for MYCN gene amplification. RESULTS: Clinical characteristics and
      survival results of 295 patients studied and 399 not studied for MYCN were
      comparable. In 48 of 295 patients studied for MYCN (16%), the gene was amplified
      (> or = three gene copies). Amplification was more frequent in children older
      than 1 year, with abdominal tumor (18% v 7%), advanced disease, normal
      vanillylmandelic (VMA) urinary excretion, and high lactate dehydrogenase (LDH),
      ferritin, and neuron-specific enolase (NSE) serum levels. In patients studied for
      MYCN, the 5-year overall survival (OS) rate was higher for children aged less
      than 1 year (90% v 44%), with extraabdominal tumor, stage 1 or 2 versus 3 versus
      4, and normal NSE, LDH, and ferritin serum levels. Patients with amplified MYCN
      had a worse OS (odds ratio [OR], 3.38; confidence interval [CI], 2.22 to 5.16).
      This association held after adjustment for other characteristics. The impact of
      MYCN amplification was greater in patients with favorable characteristics, in
      particular age (OR, 10.28 for infants; 2.08 for older children) and stage (OR,
      35.3 for stage 1 to 2; 8.41 for stage 3; 1.76 for stage 4). However, of 29
      children with stage 4s, all three with amplified MYCN survive. In a multivariate
      analysis, the prognostic role of MYCN amplification, age, and stage was
      confirmed, but the size of the effect of MYCN was dependent on age and stage.
      CONCLUSION: MYCN amplification is associated with a worse prognosis in children
      with neuroblastoma at all ages and stages except 4s. This association is most
      pronounced in children with otherwise favorable prognostic indicators, and in
      these children should be considered as an indication for more intensive
      intervention.

PMID- 8996127
TI  - Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and
      postoperative chemotherapy: a report from the Children's Cancer Group.
AB  - PURPOSE: The specific aims of this study were to improve event-free survival
      (EFS) in patients with newly diagnosed nonmetastatic osteosarcoma of an extremity
      using the histologic response to neoadjuvant chemotherapy to determine
      postoperative chemotherapy; to evaluate a uniform histologic grading system that
      measures tumor response; and to identify patient characteristics that might
      influence EFS and survival. PATIENTS AND METHODS: Two hundred sixty-eight
      patients with nonmetastatic osteosarcoma of the extremity were entered between
      August 1983 and October 1986. Preoperative chemotherapy consisted of four courses
      of high-dose methotrexate (MTX) and one course of bleomycin, cyclophosphamide,
      and dactinomycin (BCD). Histologic response to preoperative chemotherapy was
      determined by morphometric analysis. Good histologic responders (< 5% residual
      viable tumor) were treated postoperatively with MTX, BCD, and doxorubicin (DOX);
      poor histologic responders were treated with BCD, DOX, and cisplatin (CDDP).
      RESULTS: The 8-year EFS and survival rates were 53% and 60%, respectively. Two
      hundred six patients had their tumors assessed for histologic response: 28%
      displayed a good histologic response to preoperative chemotherapy. Good
      histologic responders had an 8-year postoperative EFS rate of 81% and survival
      rate of 87%; those with a poor histologic response had an 8-year postoperative
      EFS rate of 46% and survival rate of 52%. A primary tumor site in the proximal
      humerus or proximal femur and an elevated serum alkaline phosphatase level were
      associated with an increased risk of an adverse event, whereas the type of
      surgical procedure was not. CONCLUSION: EFS and survival appear to be directly
      related to histologic response to neoadjuvant chemotherapy.

PMID- 8996129
TI  - Ketamine-midazolam versus meperidine-midazolam for painful procedures in
      pediatric oncology patients.
AB  - PURPOSE: To compare the efficacy, characteristics of onset/recovery, and safety
      of ketamine/atropine/midazolam with meperidine/midazolam used as premedication
      for painful procedures in children with cancer. METHODS: A randomized, double
      blind crossover trial for two successive painful procedures (bone marrow
      aspiration or biopsy, lumbar puncture, or combined procedures) was performed at a
      referral-based pediatric hematology-oncology clinic and associated inpatient
      service of a university teaching hospital. Twenty-two children, aged 24 to 178
      months, were enrolled and 18 (81.8%) completed the double-blind, crossover trial.
      Each child received intravenous premedication with either meperidine 2 mg/kg and
      midazolam 0.1 mg/kg (MM) or atropine 0.01 mg/kg, midazolam 0.05 mg/kg, and
      ketamine 1.5 mg/kg (KM) on one occasion followed by the alternative regimen on a
      second occasion. The initial premedication regimen was chosen by random
      assignment. RESULTS: Efficacy was assessed by a trained observer using the
      Observational Scale of Behavioral Distress-Revised (OSBD-R). Operator, nurse,
      parent, and patient opinions of efficacy were recorded on a visual analog scale
      (VAS). Side effects were monitored by pulse oximetry, nasal end-tidal
      capnography, and serial blood pressure measurements. Use of KM resulted in
      significantly less procedural distress than MM (1.37 +/- 2.20 v 7.04 +/- 8.06
      OSBD-R units; P < .05). Both operators and nurses rated KM more effective than
      MM. KM use was associated with earlier readiness for the procedure (19.2 v 24.0
      minutes) and more rapid recovery (39.3 v 74.6 minutes for removal of monitoring
      devices and 58.5 v 87.1 minutes for discharge). Procedures undertaken after
      ketamine sedation were associated with fewer side effects than observed with MM
      sedation (hypoxia, 17.7% v 82.4%; hypotension, 16.6% v 55.6%; reduced respiratory
      rate, 0% v 38.9%). The incidence of emergence reactions or behavioral
      abnormalities within 24 hours postprocedure was similar in both treatment groups.
      At 7 days postprocedure, no child had persistent behavioral abnormalities and all
      children had amnesia for the procedure. Parents and children expressed a
      preference for KM over MM in 12 of 18 cases (P < .05). CONCLUSION: A
      premedication regimen of KM produced superior sedation with a faster onset and
      recovery and fewer side effects than a MM combination.

PMID- 8996130
TI  - Proposal for classifying the acute emetogenicity of cancer chemotherapy.
AB  - PURPOSE: To propose a classification of the acute emetogenicity of antineoplastic
      chemotherapy agents, and to develop an algorithm to define the emetogenicity of
      combination chemotherapy regimens. METHODS: A Medline search was conducted to
      identify (1) clinical trials that used chemotherapy as single-agent therapy, and
      (2) major reviews of antiemetic therapy. The search was limited to patients who
      received commonly used doses of chemotherapy agents, primarily by short (< 3
      hours) intravenous infusions. Based on review of this information and our
      collective clinical experience, we assigned chemotherapy agents to one of five
      emetogenic levels by consensus. A preliminary algorithm to determine the
      emetogenicity of combination chemotherapy regimens was then designed by
      consensus. A final algorithm was developed after we analyzed a data base composed
      of patients treated on the placebo arms of four randomized antiemetic trials.
      RESULTS: Chemotherapy agents were divided into five levels: level 1 (< 10% of
      patients experience acute [< or = 24 hours after chemotherapy] emesis without
      antiemetic prophylaxis); level 2 (10% to 30%); level 3 (30% to 60%); level 4 (60%
      to 90%); and level 5 (> 90%). For combinations, the emetogenic level was
      determined by identifying the most emetogenic agent in the combination and then
      assessing the relative contribution of the other agents. The following rules
      apply: (1) level 1 agents do not contribute to the emetogenic level of a
      combination; (2) adding > or = one level 2 agent increases the emetogenicity of
      the combination by one level greater than the most emetogenic agent in the
      combination; and (3) adding level 3 or 4 agents increases the emetogenicity of
      the combination by one level per agent. CONCLUSION: The proposed classification
      schema provides a practical means to determine the emetogenic potential of
      individual chemotherapy agents and combination regimens during the 24 hours after
      administration. This system can serve as a framework for the development of
      antiemetic guidelines.

PMID- 8996131
TI  - Patient preferences for oral versus intravenous palliative chemotherapy.
AB  - PURPOSE: To assess patient preference for oral versus intravenous (i.v.)
      palliative chemotherapy (CT). A strong preference would be an important quality
      of-life issue. PATIENTS AND METHODS: A structured interviewer-administered
      scenario-based questionnaire evaluated incurable cancer patients who would be
      likely to receive palliative CT in the future. Using probability trade-offs, the
      preference for route of administration was evaluated against diminishing
      treatment response. RESULTS: Of 103 assessable patients, 92 preferred oral CT, 10
      preferred i.v. CT, and one had no preference. Patient preferences were not
      associated with age, sex, site of primary cancer, or previous CT experiences.
      Major reasons for preferring oral CT were convenience, problems with i.v. access
      or needles, and a better CT-taking environment (outside of the clinic).
      Regardless of initial preference, 70% of patients were not willing to accept a
      lower response rate and 74% were not willing to accept a shorter duration of
      response to retain their initial preference. Although 99% of patients had a
      preference, 39% wanted the specific treatment decision made primarily by their
      physicians, 38% primarily by themselves, and 22% shared equally. CONCLUSION:
      Patients with incurable cancer have a clear preference for oral CT, but are
      generally not willing to sacrifice efficacy for their preference. Almost 40% of
      patients did not want to make final treatment decisions themselves.

PMID- 8996132
TI  - Determinants of postchemotherapy nausea and vomiting in patients with cancer.
      Quality of Life and Symptom Control Committees of the National Cancer Institute
      of Canada Clinical Trials Group.
AB  - PURPOSE: To assess whether prechemotherapy health-related quality-of-life (HQL)
      variables are associated with postchemotherapy nausea and vomiting (PCNV), and to
      determine their relationship to patient and treatment variables. PATIENTS AND
      METHODS: Eight hundred thirty-two chemotherapy-naive patients scheduled to
      receive antiemetic regimens containing a 5-hydroxytryptamine (5-HT3) antagonist
      with or without dexamethasone for moderately or highly emetogenic chemotherapy
      were enrolled. HQL was measured by the self-report European Organization for
      Research and Treatment of Cancer (EORTC) Care Quality of Life Questionnaire (QLQ
      C30) within 7 days before chemotherapy. Prechemotherapy HQL scores, as well as
      other patient, disease, and treatment variables were compared in the groups of
      patients who had PCNV and those who did not have PCNV. All variables were
      assessed initially in a univariate analysis and then together in a multivariate
      analysis using step-wise logistic regression. The final model generated by the
      multivariate analyses was used in a risk factor analysis to predict PCNV.
      RESULTS: Univariate analyses identified 10 HQL variables and five patient and
      treatment characteristics that were associated with PCNV. In the multivariate
      analysis, the variables remaining in the final model included low social
      functioning, prechemotherapy nausea, female gender, highly emetogenic
      chemotherapy, and the lack of maintenance antiemetics (5-HT3 antagonists with or
      without dexamethasone) after chemotherapy. A history of low alcohol use was also
      associated with PCV, whereas increased fatigue and lower performance status were
      associated with PCN. In the risk factor analysis, the incidence of PCV increased
      from 20% in those having no risk factors to 76% in those having any four of the
      six risk factors. CONCLUSION: Several pretreatment HQL, patient, and treatment
      characteristics are associated with the occurrence of PCNV. Patients about to
      receive moderately or highly emetogenic chemotherapy should be screened for these
      factors and additional measures, such as behavior modification and modification
      of antiemetic therapy, should be considered in attempts to improve the control of
      PCNV.

PMID- 8996133
TI  - Ondansetron versus metoclopramide, both combined with dexamethasone, in the
      prevention of cisplatin-induced delayed emesis. The Italian Group for Antiemetic
      Research.
AB  - PURPOSE: The role of 5-HT3 receptor antagonists in the prevention of chemotherapy
      induced delayed emesis is controversial. We compared ondansetron and
      metoclopramide, both combined with dexamethasone, in cisplatin-treated patients.
      PATIENTS AND METHODS: Three hundred twenty-two patients who had been given > or =
      50 mg/m2 of cisplatin were randomly assigned to receive, from days 2 to 4 after
      chemotherapy, oral ondansetron (8 mg twice daily) or oral metoclopramide (20 mg
      every 6 hours), both associated with intramuscular dexamethasone (8 mg twice on
      days 2 and 3, and 4 mg twice on day 4). Patients received the same intravenous
      prophylaxis for acute emesis: ondansetron 8 mg and dexamethasone 20 mg. Nausea
      and vomiting were assessed daily until day 6 after chemotherapy. RESULTS:
      According to the intention-to-treat principle, 318 patients were assessable.
      Known prognostic factors were similar in the two treatment groups. Complete
      protection from delayed vomiting and nausea was achieved by 62.0% and 43.7% of
      patients treated with ondansetron and by 60.0% and 53.7% of those receiving
      metoclopramide (no significant differences). Patients who vomited in the first 24
      hours achieved the lowest complete protection from delayed emesis. In these
      patients, ondansetron offered better complete protection from vomiting than
      metoclopramide (28.6% v 3.8%, P < .05). Both treatments were well tolerated.
      CONCLUSION: The two treatments offer similar protection from delayed emesis,
      although ondansetron plus dexamethasone may be preferred in patients who suffer
      from acute vomiting. Optimal control of acute emesis is essential to achieve good
      protection from delayed nausea and vomiting, irrespective of the antiemetic
      treatment received.

PMID- 8996134
TI  - Evaluation of new bone resorption markers in a randomized comparison of
      pamidronate or clodronate for hypercalcemia of malignancy.
AB  - PURPOSE: To compare the effects of two bisphosphonates on markers of bone
      resorption in a randomized double-blind trial for the treatment of hypercalcemia
      of malignancy. PATIENTS AND METHODS: Thirty-two patients with a serum calcium
      (sCa) level > or = 2.7 mmol/L that persisted after 48 hours of saline rehydration
      were randomized to receive pamidronate 90 mg or clodronate 1,500 mg. Bone
      resorption markers measured included urinary calcium (uCa), hydroxyproline (Hyp),
      deoxypyridinoline (Dpd), pyridinoline (Pyd), the cross-linking molecule at either
      the N-telopeptide (NTx) or the C-telopeptide (Crosslaps) regions of type I
      collagen, and free Dpd. RESULTS: Both bisphosphonates restored normocalcemia, but
      the duration of action was longer after pamidronate (P < .01). There was a mean
      pretreatment sevenfold increase in NTx, fivefold increase in Dpd and Crosslaps,
      and 2.5-fold increase in free Dpd. The changes in uCa were confounded by an
      increase in parathyroid hormone (PTH) (P < .05), which, through effects on the
      kidney, inhibits calcium excretion. Most resorption markers showed a larger
      decrease after pamidronate than clodronate (P < .01). NTx and Crosslaps showed
      the greatest decrease, being significantly different from any other marker in
      both arms (P < .01). There was a significant correlation between Dpd, NTx, and
      Crosslaps (P < .002), but not with uCa. CONCLUSION: The superiority of
      pamidronate in controlling hypercalcemia is mirrored by the changes observed in
      these markers. uCa is not an accurate bone resorption marker, which reflects the
      renal handling of calcium by PTH. NTx and Crosslaps showed the largest increase
      at baseline and the greatest change after treatment, which suggests these new
      markers may be more sensitive indicators of bone resorption.

PMID- 8996135
TI  - Improved management of invasive pulmonary aspergillosis in neutropenic patients
      using early thoracic computed tomographic scan and surgery.
AB  - PURPOSE: The prognosis of invasive pulmonary aspergillosis (IPA) occurring in
      neutropenic patients remains poor. We studied whether new strategies for early
      diagnosis could improve outcome in these patients. PATIENTS AND METHODS: Twenty
      three histologically proven and 14 highly probable IPAs in 37 hematologic
      patients (neutropenic in 36) were analyzed retrospectively. RESULTS: The most
      frequent clinical signs associated with IPA were cough (92%), chest pain (76%),
      and hemoptysis (54%). Bronchoalveolar lavage (BAL) was positive in 22 of 32
      cases. Aspergillus antigen test was positive in 83% of cases when tested on BAL
      fluid. Since October 1991, early thoracic computed tomographic (CT) scans were
      systematically performed in febrile neutropenic patients with pulmonary x-ray
      infiltrates. This approach allowed us to recognize suggestive CT halo signs in
      92% of patients, compared with 13% before this date, and the mean time to IPA
      diagnosis was reduced dramatically from 7 to 1.9 days. Among 36 assessable
      patients, 10 failed to respond (amphotericin B [AmB] plus fluorocytosyne, n = 2;
      itraconazole + AmB, n = 8) and died of aspergillosis. Twenty-six patients were
      cured or improved by antifungal treatment (itraconazole with or without AmB, n =
      22; voriconazole, n = 4). In 15 of 16 cases, surgical resection was combined
      successfully with medical treatment. Achievement of hematologic response, early
      diagnosis, unilateral pulmonary involvement, and highest level of fibrinogen
      value < 9 g/L were associated with better outcome. CONCLUSION: In febrile
      neutropenic patients, systematic CT scan allows earlier diagnosis of IPA. Early
      antifungal treatment, combined with surgical resection if necessary, improves IPA
      prognosis dramatically in these patients.

PMID- 8996136
TI  - Dose-escalation and pharmacodynamic study of topotecan in combination with
      cyclophosphamide in patients with refractory cancer.
AB  - PURPOSE: Based on preclinical data that demonstrated synergy between alkylating
      agents and topoisomerase (topo) I poisons, we determined the maximum-tolerated
      dose (MTD) of topotecan, using a 5 day bolus schedule, that could be given in
      combination with a single, fixed dose of cyclophosphamide. Pharmacodynamics of
      this combination were explored by analyzing biochemical effects of treatment in
      peripheral-blood mononuclear cells (PBMCs). PATIENTS AND METHODS: Patients with
      refractory cancer were treated with cyclophosphamide 600 mg/m2 on day 1, followed
      by topotecan given as a 30-minute infusion for 5 consecutive days. Cycles were
      repeated every 3 weeks. Once the MTD was defined, granulocyte colony-stimulating
      factor (G-CSF) was added to the regimen in an attempt to escalate further the
      dose of topotecan. Plasma concentrations of topotecan were determined during the
      first treatment cycle by high-performance liquid chromatography. PBMCs were
      sampled at baseline and throughout the 5-day treatment period for analysis of
      topo I protein concentrations and to determine drug-induced DNA fragmentation.
      RESULTS: Twenty-six patients were treated with topotecan at doses that ranged
      from 0.5 mg/m2/d to 1.2 mg/ m2/d for a total of 74 cycles. Reversible neutropenia
      was dose-limiting, with mild to moderate suppression of the other blood-cell
      elements commonly occurring. Transfusions of RBCs and platelets were required in
      24% and 7% of treatment cycles, respectively. The most prominent nonhematologic
      toxicities were fatigue and weight loss. Compared with previously published data
      in which topotecan was administered alone, cyclophosphamide did not appear to
      alter the pharmacokinetics of topotecan. Significant increases in topo I
      concentration were identified in PBMCs following the administration of
      cyclophosphamide on day 1 and there was a significant decrease in topo 1 during
      the 5-day course of treatment (P < .01, sign test). DNA fragmentation as a result
      of drug treatment was identified in 11 of 15 (73%) cycles analyzed. CONCLUSION:
      For previously treated patients, the recommended dose of topotecan in this
      schedule is 0.75 mg/m2/d without growth factor support and 1.0 mg/ m2/d if it is
      administered with G-CSF. Biochemical changes in cells induced by exposure to
      camptothecins can be measured in vivo and these effects may have important
      implication in the design of combination therapies and the optimal scheduling of
      this class of agents.

PMID- 8996137
TI  - Phase I clinical trial of melphalan and 41.8 degrees C whole-body hyperthermia in
      cancer patients.
AB  - PURPOSE: To evaluate the biologic interactions and toxicities of melphalan (L
      PAM) combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes.
      PATIENTS AND METHODS: Sixteen patients with refractory cancer were treated (May
      1992 to May 1995) with WBH alone during week 1) thereafter patients were
      randomized to receive either L-PAM alone on week 2 and L-PAM plus WBH on week 5,
      or the reverse sequence. Patients who demonstrated clinical improvement received
      WBH plus L-PAM monthly. Dose levels of L-PAM were 10 mg/m2 (n = 3), 15 mg/m2 (n =
      3), 17.5 mg/m2 (n = 6), and 20 mg/m2 (n = 4). L-PAM was administered at target
      temperature; WBH was administered with an Aquatherm radiant-heat device (patent
      pending; Cancer Research Institute, New York, NY). RESULTS: Comparisons of mean
      WBC count and platelet nadirs for L-PAM alone and L-PAM plus WBH demonstrated
      that the addition of WBH resulted in nadir counts that were, on average, 25%
      lower. There were no instances of febrile neutropenia or bleeding. Toxicities
      allowed for escalation of L-PAM to 20 mg/m2; all four patients at this level
      experienced grade 4 myelosuppression. No significant myelosuppression was
      observed at 10 and 15 mg/m2. Grade 3 myelosuppression was observed in two of six
      patients at 17.5 mg/m2. Responses included complete remission (CR) of pancreatic
      cancer (10 mg/m2), partial remission (PR) of malignant melanoma in two patients
      (20 mg/m2), and transient clinical and/or serologic improvement in five patients.
      The pharmacokinetics of L-PAM were not altered by WBH. Observed cytokine
      induction by WBH is also discussed in detail. CONCLUSION: We conclude that L-PAM
      with 41.8 degrees C WBH is well tolerated. Clinical results are consistent with
      preclinical predictions and provide a foundation for second-generation trials now
      in progress.

PMID- 8996138
TI  - Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin
      plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic
      Oncology Group study.
AB  - PURPOSE: Cisplatin, mitolactol (dibromodulcitol), and ifosfamide have been the
      most active single agents in squamous carcinoma of the cervix identified so far
      by the Gynecologic Oncology Group (GOG). Combinations of cisplatin plus
      ifosfamide and cisplatin plus mitolactol are prospectively compared with
      cisplatin alone. PATIENTS AND METHODS: Patients were randomized to receive
      cisplatin 50 mg/m2 or the same dose of cisplatin plus mitolactol (C + M) 180
      mg/m2 orally on days 2 to 6, or cisplatin plus ifosfamide (CIFX) 5 g/m2 given as
      a 24-hour infusion plus mesna 6 g/m2 during and for 12 hours after the ifosfamide
      infusion, every 3 weeks for up to six courses. Of 454 patients entered, 438 were
      eligible and analyzed for response and survival. RESULTS: CIFX had a higher
      response rate (31.1% v 17.8%, p = .004) and longer progression-free survival
      (PFS) time (P = .003) compared with cisplatin alone. The median times to
      progression or death were 4.6 and 3.2 months, respectively. C + M showed no
      significant improvement in these parameters compared with cisplatin alone.
      Survival was associated with initial performance score (PS; 0 was more favorable;
      P < .001) and with age (younger was unfavorable, P = .025). There was no
      significant difference in overall survival between cisplatin and either of the
      combinations. Leukopenia, renal toxicity, peripheral neurotoxicity, and CNS
      toxicity were more frequent with CIFX (P < .05). CONCLUSION: CIFX improved the
      response rate and PFS duration in advanced cervix cancer compared with cisplatin
      alone, but at the cost of greater toxicity and with no improvement in survival.

PMID- 8996139
TI  - Phase II trial of oral altretamine for relapsed ovarian carcinoma: evaluation of
      defining response by serum CA125.
AB  - PURPOSE: A phase II study was performed of oral altretamine in 71 patients with
      ovarian carcinoma who entered clinical complete remission with CA125 levels less
      than 35 U/mL after initial or second-line chemotherapy, and relapsed more than 6
      months later. Response was compared between standard and CA125-based criteria.
      PATIENTS AND METHODS: Altretamine 260 mg/m2 was given in divided doses daily for
      14 days per month. Response was evaluated according to European Organization for
      Research and Treatment of Cancer (EORTC) criteria in 45 of 66 eligible patients.
      Response was assessed according to precise CA125 criteria in 51 patients based on
      either a confirmed > or = 50% or > or = 75% decrease in CA125 levels. RESULTS: A
      combination of domperidone, dexamethasona, and chlorpromazine at night controlled
      toxicity in most patients, which was mainly nausea (National Cancer Institute
      criteria grade 2 or 3 in 27), vomiting (grade 2 or 3 in 19, grade 4 in one), and
      tiredness (grade 2 or 3 in 15). Responses (complete plus partial) were seen in 18
      (40%; 95% confidence interval [CI], 25.4% to 54.6%) of those evaluated according
      to EORTC criteria and in 20 (39%; 95% CI, 25.5% to 52.9%) of those evaluated
      according to CA125 level. The overall response rate was 26 of 57 (45.6%) and was
      related to treatment-free interval: 6 to 12 months, 35%; 12 to 24 months, 52%;
      and greater than 24 months, 67%. The medium duration of response was 8 months.
      CONCLUSION: Oral altretamine is a useful agent in patients-who relapse after
      previously responsive ovarian cancer. Response evaluation by a strict CA125
      definition gave a similar estimate of the efficacy of altretamine as EORTC
      criteria.

PMID- 8996140
TI  - Phase I trial and pharmacologic trial of sequences of paclitaxel and topotecan in
      previously treated ovarian epithelial malignancies: a Gynecologic Oncology Group
      study.
AB  - PURPOSE: A phase I and pharmacologic study to evaluate the feasibility of
      administering paclitaxel (PTX) in combination with topotecan (TPT) without and
      with granulocyte colony-stimulating factor (G-CSF) in women with recurrent or
      refractory ovarian cancer. PATIENTS AND METHODS: TPT was administered as a 30
      minute infusion daily for 5 days and PTX was given as a 24-hour infusion (PTX-24)
      either before TPT on day 1 or after TPT on day 5. Each patient received both
      schedules on an alternating basis every 3 weeks. Sequential dose escalation of
      TPT or PTX-24 without and with G-CSF resulted in five dosage permutations of
      TPT/PTX (mg/ m2): 0.75/135 without G-CSF and 0.75/135, 1.25/135, 1.50/135, and
      1.25/170 with G-CSF. RESULTS: Twenty-two patients received 109 courses of
      therapy. Dose-limiting myelosuppression consistently occurred at the first
      TPT/PTX-24 dose level (0.75/135 mg/m2) in the absence of G-CSF support. Although
      the addition of G-CSF resulted in reduced rates of complicated neutropenia, the
      incidences of dose-limiting neutropenia and thrombocytopenia were unacceptably
      high after the doses of either TPT or PTX-24 were increased. Paired analysis
      showed similar hematologic toxicities between the two sequences of drug
      administration. The pharmacologic behavior of both TPT and PTX-24 was not altered
      by drug sequencing. Major antitumor responses occurred in 40% of patients with
      measurable and assessable disease, including 45% and 9% of patients with
      potentially cisplatin-sensitive and -resistant tumors, respectively. CONCLUSION:
      The recommended doses of TPT on a daily times-five schedule combined with PTX-24
      in these patients were 0.75 mg/m2/d and 135 mg/m2, respectively, with G-CSF
      support. Although this dose of PTX has significant single-agent activity in
      ovarian cancer, the dose of TPT is much lower than the TPT dose at which single
      agent activity has been observed. Due to the inability to administer near
      relevant single-agent doses of both drugs in combination, as well as the
      requirement for G-CSF support, further evaluations of this regimen in women with
      refractory or recurrent ovarian cancer are necessary before it can be recommended
      for previously treated patients in this setting.

PMID- 8996142
TI  - Dose-effect study of carboplatin in ovarian cancer: a Danish Ovarian Cancer Group
      study.
AB  - PURPOSE: To elucidate the effect of a doubled carboplatin dose-intensity in
      epithelial ovarian cancer in combination with a fixed dose of cyclophosphamide.
      PATIENTS AND METHODS: A total of 222 patients with epithelial ovarian cancer
      stages II to IV were included in the study. Following surgery, patients were
      randomly assigned to receive carboplatin at an area under the concentration
      versus-time curve (AUC) of 4 (AUC4) or carboplatin at an AUC of 8 (AUC8) and
      cyclophosphamide 500 mg/m2 given every 4 weeks for six courses. The AUC was
      calculated according to Calvert's formula. In 123 patients, the carboplatin AUC
      was also measured based on a single-sample method and the results were compared
      with the calculated AUC. The end points of the trial were complete pathologic
      remission (CPR) and crude survival. RESULTS: Approximately 50% of patients in
      both arms underwent second-look surgery. The frequency of CPR was 32% and 30%,
      respectively. The survival curves showed no significant difference (P = .84). The
      dose-intensity of cyclophosphamide was almost identical in the two arms, whereas
      that of carboplatin was different. In the AUC8 arm, the dose-intensity was 1.86
      times that of the AUC4 arm. The results also demonstrated good agreement between
      the calculated and the measured AUC in most patients. Bone marrow toxicity was
      significantly higher in the AUC8 arm. CONCLUSION: A doubling of the carboplatin
      dose-intensity did not result in any significant improvement of pathologic
      remission or survival. Calvert's formula can be used to give a fairly accurate
      estimate of the carboplatin AUC. Bone marrow toxicity increased with higher dose
      intensity, and a further increase of dose is only feasible with growth-factor or
      stem-cell support.

PMID- 8996141
TI  - Phase I and pharmacologic study of paclitaxel administered weekly in patients
      with relapsed ovarian cancer.
AB  - PURPOSE: Paclitaxel has shown significant activity in advanced ovarian cancer. In
      vitro studies with paclitaxel have suggested that fractionated brief infusion
      schedules may be more effective than the standard 24-hour infusion. We commenced
      a phase I evaluation of escalating-dose paclitaxel (40, 50, 60, 80, 100 mg/m2)
      administered weekly as a 1-hour infusion in patients with recurrent ovarian
      cancer. All patients had received prior paclitaxel and cisplatin therapy. All
      patients received standard premedication. PATIENTS AND METHODS: Eighteen patients
      are assessable on this phase I study. The mean age was 54 years (range, 48 to
      74). The median number of prior chemotherapy regimens was three (range, two to
      five). The mean paclitaxel-free interval was 10.1 months (range, 1 to 24).
      RESULTS: A total of 194 cycles of therapy were administered, with a mean of 10
      (range, one to 12) per patient. No mucositis or grade III neuropathy was seen.
      Alopecia occurred in one out of 18 assessable patients. The mean neutrophil nadir
      was 4.0 x 10(9)/L. At the top dose level (100 mg/m2) delivered, dose-intensity
      was 90.75% of that planned and greater than two fold the standard dose-intensity.
      Partial responses were seen in four of 13 assessable patients (30%). Two patients
      with progression of disease on standard three-week paclitaxel schedules switched
      to a weekly schedule with demonstrated response. Increasing paclitaxel dose
      correlated with measured area under the curve (AUC) (R2 = .614). Dose-limiting
      toxicity was reached at 100 mg/m2 with two of three patients experiencing a
      treatment delay, thus defining a maximum-tolerated dose of 80 mg/m2 in this group
      of heavily pretreated patients on this weekly schedule. CONCLUSION: (1)
      Paclitaxel administered as a 1-hour infusion is well tolerated; (2) this schedule
      of administration does not result in cumulative myelosuppression; and (3) this
      schedule of administration results in dose-intensive paclitaxel delivery with a
      favorable toxicity profile.

PMID- 8996143
TI  - Neurotoxicity and ototoxicity of cisplatin plus paclitaxel in comparison to
      cisplatin plus cyclophosphamide in patients with epithelial ovarian cancer.
AB  - PURPOSE: To compare the neurotoxicity and ototoxicity of combination cisplatin
      plus paclitaxel versus cisplatin plus cyclophosphamide using extensive clinical
      and instrumental evaluation. PATIENTS AND METHODS: Forty-six of 51 consecutive
      patients affected by-epithelial ovarian cancer seen in our institution between
      October 1994 and August 1995 entered the study. After randomization, they were
      assigned to receive cisplatin 75 mg/m2 every 3 weeks associated with
      cyclophosphamide 750 mg/m2 (CC group, n = 22) or paclitaxel 175 mg/m2 over a 3
      hour infusion (CP group, n = 24). Treatment was repeated six times in 43 patients
      and nine times in 25. Before treatment and after three, six, and nine courses of
      chemotherapy, patients underwent clinical and instrumental neurologic and
      otologic examinations. RESULTS: Mild sensory impairment was evident even after
      only three courses of both treatments and signs and symptoms were more severe at
      the end of treatment. On clinical grounds only, it was possible to demonstrate
      after six and nine courses a difference between CC and CP treatment, due to the
      involvement in some CP patients of pain and thermal sensory modalities. However,
      the overall severity of the neuropathy was similar. Audiometric parameters
      demonstrated a more negative outcome after treatment in CC compared with CP
      patients. However, the different severity of the involvement was closely
      correlated to this initial difference in audiologic performance. CONCLUSION: Up
      to nine courses of chemotherapy, the CC and CP schedules are similar in terms of
      severity of neurotoxicity and ototoxicity when patients are evaluated during and
      immediately after treatment. With the doses used in our study, these toxicities
      are not dose-limiting. Our results suggest that most of the toxic effects
      observed during the treatment were due to cisplatin.

PMID- 8996144
TI  - Hormonal therapy prolongs survival in irradiated locally advanced breast cancer:
      a European Organization for Research and Treatment of Cancer Randomized Phase III
      Trial.
AB  - PURPOSE: To assess the long-term contribution of adjuvant chemotherapy (CT) and
      hormonal therapy (HT) in patients with locally advanced breast cancer, and to
      evaluate the impact of time of analysis on the results during accrual and up to 8
      years after closure of a randomized phase III trial. MATERIALS AND METHODS: In a
      trial using a factorial design, 410 patients were randomized between radiotherapy
      (RT) alone, RT plus CT, RT plus HT, and RT plus HT plus CT. RESULTS: CT and HT
      each produced a significant prolongation of the time to locoregional tumor
      recurrence and to distant progression of disease, with the combined treatments
      providing the greatest therapeutic effect. At the time of trial closure, a
      significant improvement of survival was observed in patients who received CT (P =
      .004); however, with a longer follow-up duration, this effect disappeared (P >
      .05). HT did not initially appear to improve survival (P = .16); however, in the
      latest analysis with a long-term follow-up duration, a significant improvement of
      survival was seen (P = .02). A consistent 25% reduction in the death hazards
      ratio has been seen at all evaluations since trial closure in patients who
      received HT. The best survival results were observed in patients who received RT,
      HT, and CT (P = .02), with a reduction of 35% in the death hazards ratio.
      CONCLUSION: An improvement in survival attributable to HT has been shown in
      patients with locally advanced breast cancer. The greatest therapeutic effect was
      seen in the treatment group that received both CT and HT. The improvement
      obtained with HT became apparent only after long-term follow-up evaluation.

PMID- 8996145
TI  - Compliance with practice guidelines for node-negative breast cancer.
AB  - PURPOSE: Practice guidelines for cancer management have been in use in the
      province of British Columbia (BC), Canada, since the mid 1970s. To evaluate
      practice guideline compliance, treatment received was compared with treatment
      recommended in a population-based cohort of women with breast cancer. METHODS:
      All incident cases (n = 939) of invasive, pathologically node-negative breast
      cancer diagnosed in 1991 were identified from the BC Cancer Registry. Treatment
      details were abstracted from cancer clinic records for cases referred to the BC
      Cancer Agency (BCCA) (n = 661) and original source documents for nonreferred
      cases. Management decisions were considered compliant if the patient received the
      recommended treatment or was entered onto a randomized trial of the modality
      being assessed. RESULTS: Overall compliance with adjuvant therapy guidelines was
      97% for radiotherapy, 96% for chemotherapy, and 89% for tamoxifen. An oncology
      specialist was consulted by 94% of patients with an indication for adjuvant
      treatment and by 58% of those without an indication (odds ratio [OR] = 10.7; 95%
      confidence interval, 7.0 to 16.4). Compliance with a guideline to deliver
      radiotherapy was 95%; with chemotherapy, 77%; and with tamoxifen, 68%. Compliance
      with a guideline that stated no adjuvant treatment was indicated was 99% for
      radiotherapy, 98% for chemotherapy, and 92% for tamoxifen. Noncompliance among
      patients with an indication for treatment was related to nonreferral to an
      oncology specialist and less complete implementation of guideline changes in the
      community as compared with cancer center practices. CONCLUSION: Compliance was
      high, but scheduled updating and more effective community implementation could
      further improve consistency of care.

PMID- 8996146
TI  - Complications after treatment with external-beam irradiation in early-stage
      prostate cancer patients: a prospective multiinstitutional outcomes study.
AB  - PURPOSE: To use data from a prospective quality-of-life study to assess
      differences in disease-specific and general health-related quality-of-life
      changes after treatment with different external-beam irradiation techniques for
      prostate cancer. PATIENTS AND METHODS: Patients were divided into three groups
      based on their pretreatment field size and planning technique: whole pelvis,
      small field, or conformal. Measures of bowel, urinary, and sexual function and of
      global health-related quality-of-life parameters (from the Health Survey Short
      Form [SF-36] and the Profile of Mood States [POMS]) were obtained from self
      report questionnaires completed before initiation of therapy and at 3 and 12
      months after therapy. RESULTS: Irritative gastrointestinal and genitourinary side
      effects were frequent 3 months after treatment, but were substantially improved
      at 12 months. Sexual dysfunction increased steadily over the study period. The
      POMS and the SF-36 did not demonstrate significant changes over time. Despite
      small patient numbers, we found trends in favor of conformal therapy across
      several symptom measures, including sexual function. In the fatigue, energy, and
      vigor subscales, patients who received whole-pelvis treatment fared significantly
      worse than those in the other two groups. CONCLUSION: Prospective, detailed data
      from a feasibility study allowed us to assess the effect of technique on quality
      of life following external-beam irradiation. Although limited by the small
      planned sample size, these results suggest that smaller radiation fields limit
      treatment-related complications, including, unexpectedly, sexual dysfunction.
      However, confirmation in a larger study is necessary.

PMID- 8996147
TI  - Increasing prostate-specific antigen profile following definitive radiation
      therapy for localized prostate cancer: clinical observations.
AB  - PURPOSE: To examine the natural history of patients who have received definitive
      radiation therapy alone for clinically localized prostate cancer and have an
      increasing prostate-specific antigen (PSA) profile. PATIENTS AND METHODS: One
      hundred fifty-one men with an increasing PSA profile after definitive
      radiotherapy were identified. The subsequent natural history of these men,
      including local recurrence, distant metastasis, and survival, was examined. In
      119 men, posttreatment PSA doubling times (PSADT) were calculated using linear
      regression. Cox regression models were used to examine the effect of clinical and
      treatment variables on clinical failure and survival. RESULTS: Patients with high
      pretreatment PSA values, high Gleason scores, and T3 tumors were more likely to
      develop a PSA elevation. The median calculated post-treatment PSADT was 13
      months, and 95% of patients had posttreatment PSADT of less than 3 years. PSADT
      was correlated with tumor stage and Gleason score. Five years after PSA
      elevation, the estimated rate of clinical local recurrence is 26% and the
      estimated rate of distant metastases is 47%. Rapid PSADT (< 12 months) and a
      short interval from the end of treatment to PSA elevation (< 12 months) were
      significant independent predictors of distant metastases. The estimated rates of
      overall and cause-specific survival 5 years after PSA elevation are 65% and 76%,
      respectively. Gleason grade is the only significant independent predictor of
      overall and cause-specific survival after PSA elevation. CONCLUSION: The natural
      history of men who have an increasing PSA profile following definitive
      radiotherapy is heterogeneous. In the absence of salvage therapy, at least three
      quarters of men will have clinical evidence of recurrent disease 5 years after a
      PSA elevation is detected. Men with a rapid posttreatment PSADT and a short
      interval from the end of treatment to an increasing PSA profile are at a very
      high risk of developing distant metastasis within 5 years of PSA elevation.

PMID- 8996148
TI  - Fertility after chemotherapy for testicular germ cell cancers.
AB  - PURPOSE: To analyze the probability of recovery of spermatogenesis after
      orchidectomy and cisplatin-based chemotherapy (CT) for testicular germ cell
      cancer. PATIENTS AND METHODS: One hundred seventy-eight patients treated between
      1979 and 1991 were selected by the requirement of sperm count both pre-CT and
      post-CT. Counts were classified as normospermic (NS) if more than 10 x 10(6)/mL,
      oligospermic (OS) if 1 to 9 x 10(6)/mL, and azoospermic (AS) if less than 1 x
      10(6)/mL. The median follow-up time after CT before sperm analysis was 30 months.
      RESULTS: Analysis of 170 patients whose spermatogenesis was reassessed at least 1
      year after CT showed that of 89 patients whose pre-CT counts were NS, the post-CT
      count was NS in 64%, OS in 16%, and AS in 20%. There was clear evidence for
      continued recovery beyond 1 year; the probability of spermatogenesis increased to
      48% by 2 years and 80% by 5 years. There was a significantly higher probability
      of recovery to OS and NS count levels in the 54 patients treated with carboplatin
      rather than cisplatin-based therapy. There was an independent and similar effect
      of normal pre-CT count. There was a reduced probability to recover to OS in the
      26 patients treated with more than four cycles of CT. A prognostic model
      identified three groups with 25%, 45%, and 82% probabilities of recovering
      spermatogenesis by 2 years after CT. CONCLUSION: Analysis of pre-CT sperm count
      together with details of planned treatment can be used to predict recovery of
      spermatogenesis following germ cell CT.

PMID- 8996149
TI  - Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as
      postoperative adjuvant therapy for colon cancer.
AB  - PURPOSE: The goal of this study was to determine the efficacy of intensive-course
      fluorouracil (5FU) plus low-dose leucovorin given for 6 months following
      potentially curative resection of colon cancer. PATIENTS AND METHODS: Three
      hundred seventeen patients with high-risk stage II or stage III colon cancer were
      randomly assigned 3 to 4 weeks following surgery to receive either (1)
      chemotherapy with six cycles of 5FU (425 mg/m2) plus leucovorin (20 mg/m2) by
      rapid intravenous injection daily for 5 consecutive days every 4 to 5 weeks, or
      (2) observation. RESULTS: The median follow-up duration is 72 months for patients
      still alive. Patients who received postoperative 5FU plus leucovorin experienced
      significant improvement in time to relapse (P < .01) and survival (P = .02)
      compared with control patients treated with surgery alone. Stomatitis, diarrhea,
      and leukopenia were the predominant chemotherapy toxicities. There were no
      treatment-related deaths. CONCLUSION: These results indicate that intensive
      course 5FU plus low-dose leucovorin is effective in preventing tumor relapse and
      improving survival in patients with high-risk colon cancer. These benefits were
      seen with only six cycles of treatment, using low-dose leucovorin in combination
      with 5FU on a schedule convenient for outpatient administration.

PMID- 8996150
TI  - Phase II study of irinotecan in the treatment of advanced colorectal cancer in
      chemotherapy-naive patients and patients pretreated with fluorouracil-based
      chemotherapy.
AB  - PURPOSE: To assess the efficacy of irinotecan (CPT-11) in the treatment of
      advanced colorectal cancer in both chemotherapy-naive and pretreated patients.
      PATIENTS AND METHODS: Two hundred thirteen patients (aged 18 to 75 years) with
      metastatic colorectal cancer, World Health Organization (WHO) performance status
      < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2
      every 3 weeks. All 178 patients eligible for efficacy analysis had not received
      more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or
      palliative) and had adequate hematologic, renal, and hepatic function. RESULTS:
      Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of
      the patients had > or = two metastatic sites. Ninety-eight percent of the
      patients had undergone previous surgery, and 77.5% had received prior
      chemotherapy. Thirty-two of 178 eligible patients achieved on objective response
      (four complete responses [CRs] and 28 partial responses [PRs]; response rate,
      18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed.
      The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy
      naive group. Within the former subgroup, response rates of 16.1% were reported in
      patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients
      who were progressive off such treatment. The median duration of objective
      response (9.1 months) and median time to achievement of a response (9.3 weeks)
      did not differ between chemotherapy-naive and pretreated patients. The most
      frequent adverse events were neutropenia, which developed in 80% of the patients,
      delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%).
      All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia
      was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in
      11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4
      neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of
      greatest concern. CONCLUSION: CPT-11 has definite activity in the treatment of
      advanced metastatic colorectal cancer both in chemotherapy-naive and in
      pretreated patients who experienced disease progression on 5-FU, which suggests a
      lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the
      major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic
      sepsis.

PMID- 8996151
TI  - Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus
      fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.
AB  - PURPOSE: We report the results of a prospectively randomized study that compared
      the combination of epirubicin, cisplatin, and protracted venous infusion
      fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU,
      doxorubicin, and methotrexate (FAMTX) in previously untreated patients with
      advanced esophagogastric cancer. PATIENTS AND METHODS: Two hundred seventy-four
      patients with adenocarcinoma or undifferentiated carcinoma were randomized and
      analyzed for survival, tumor response, toxicity, and quality of life (QL).
      RESULTS: The overall response rate was 45% (95% confidence interval [CI], 36% to
      54%) with ECF and 21% (95% CI, 13% to 29%) with FAMTX (P = .0002). Toxicity was
      tolerable and there were only three toxic deaths. The FAMTX regimen caused more
      hematologic toxicity and serious infections, but ECF caused more emesis and
      alopecia. The median survival duration was 8.9 months with ECF and 5.7 months
      with FAMTX (P = .0009); at 1 year, 36% (95% CI, 27% to 45%) of ECF and 21% (95%
      CI, 14% to 29%) of FAMTX patients were alive. The median failure-free survival
      duration was 7.4 months with ECF and 3.4 months with FAMTX (P = .00006). The
      global QL scores were better for ECF at 24 weeks, but the remaining QL data
      showed no differences between either arm of the study. Hospital-based cost
      analysis on a subset of patients was similar for each arm and translated into an
      increment cost of $975 per life-year gained. CONCLUSION: The ECF regimen results
      in a survival and response advantage, tolerable toxicity, better QL and cost
      effectiveness compared with FAMTX chemotherapy. This regimen should now be
      considered the standard treatment for advanced esophagogastric cancer.

PMID- 8996152
TI  - Chemotherapy as an adjunct to radiation in the treatment of squamous cell
      carcinoma of the head and neck: results of the Yale Mitomycin Randomized Trials.
AB  - PURPOSE: Two consecutive randomized trials were run at our institution using the
      bioreductive alkylating agent mitomycin as an adjunct to radiation therapy in an
      effort to improve outcome in patients with squamous cell carcinoma of the head
      and neck. METHODS: Between 1980 and 1992, two consecutive randomized trials using
      mitomycin (trial 1) and mitomycin with dicumarol (trial 2) as an adjunct to
      radiation therapy in patients with squamous cell carcinoma of the head and neck
      were conducted at our institution. The patients were stratified by intent of
      therapy, extent of disease, and primary tumor site. Within each strata, patients
      were randomized to receive radiation therapy with or without mitomycin (trial 1)
      or mitomycin/dicumarol (trial 2). RESULTS: A total of 203 patients were enrolled
      onto both trials, 195 of whom were eligible for analysis. Patients were equally
      balanced with respect to sex, age, extent of disease, primary site, radiation
      dose, and total duration of radiation treatment. Hematologic toxicities were more
      frequently noted in the drug-treated arms, but were acceptable with no drug
      related treatment deaths. Nonhematologic toxicities were acceptable and not
      significantly different between the two arms. As of September 1995, with a median
      follow-up of 138 months, a statistically significant benefit occurred in the
      mitomycin arms with respect to cause-specific survival (0.74 +/- 0.05 v 0.51 +/-
      0.05; P = .005), local recurrence-free survival (0.85 +/- 0.04 v 0.66 +/- 0.05; P
      = .002), and local regional recurrence-free survival (0.76 +/- 0.05 v 0.54 +/-
      0.05; P = .003). No statistically significant difference in overall survival was
      obtained (0.48 +/- 0.05 mitomycin arms v 0.42 +/- 0.05 radiation alone).
      CONCLUSION: The bioreductive alkylating agent mitomycin is a safe and effective
      adjunct to radiation therapy in the treatment of squamous cell carcinoma of the
      head and neck. The statistically and clinically significant improvement in local
      regional relapse and cause-specific survival obtained support the use of
      mitomycin as an adjunct to radiation therapy in the management of squamous cell
      carcinoma of the head and neck.

PMID- 8996153
TI  - Progress report of combined chemoradiotherapy versus radiotherapy alone in
      patients with esophageal cancer: an intergroup study.
AB  - PURPOSE: The present intergroup phase III randomized study compared combined
      chemotherapy (CT) plus radiotherapy (RT) treatment versus RT only in patients
      with locally advanced esophageal cancer. MATERIALS AND METHODS: Two courses of
      chemotherapy during 50 Gy RT followed by additional two courses of the same CT,
      versus 64 Gy RT alone were investigated. CT consisted of cisplatin 75 mg/m2 on
      day 1 [corrected] and fluorouracil (5FU) 1,000 mg/m2/d on days 1 to 4 every 4
      weeks with RT and every 3 weeks post-RT. The main objective of the study was to
      compare overall survival between the two randomized treatment groups. Patients
      were stratified by tumor size, histology, and degree of weight loss. RESULTS:
      Sixty-two assessable patients were randomized to receive RT alone, and 61 to the
      combined arm. Patients characteristics were as follows: squamous cell cancer, 90%
      versus 85%; weight loss greater than 10 lb, 61% versus 69%; and tumor size, > or
      = 5 cm, 82% versus 80% on the RT and CT-RT arms, respectively. Systemic side
      effects, which consisted of nausea, vomiting, and renal and myelosuppression,
      occurred more frequently on the combined arm, while local side effects were
      similar in both groups. With a minimum follow-up time of 5 years for all
      patients, the median survival duration was 14.1 months and the 5-year survival
      rate was 27% in the combined treatment group, while the median survival duration
      was 9.3 months with no patients alive at 5 years in the RT-alone group (P <
      .0001). Additional patients (69) were treated with the same combined therapy and
      were analyzed. The results of the last group confirmed all of the results
      obtained with combined CT-RT in the randomized trial, with a median survival
      duration of 17.2 months and 3-year survival rate of 30%. CONCLUSION: We conclude
      that cisplatin and 5FU infusion given during and post-RT of 50 Gy is
      statistically superior to standard 64-Gy RT alone in patients with locally
      advanced esophageal cancer.

PMID- 8996154
TI  - Mutational activation of the K-ras oncogene and the effect of chemotherapy in
      advanced adenocarcinoma of the lung: a prospective study.
AB  - PURPOSE: To determine whether the clinical course and the response to
      chemotherapy of patients with advanced adenocarcinoma of the lung depends on the
      presence or absence of a ras mutation in the tumor. Mutational activation of K
      ras is a strong adverse prognostic factor in stage I or II lung cancer and
      laboratory studies have suggested that ras mutations lead to resistance against
      ionizing radiation and chemotherapy. PATIENTS AND METHODS: Patients with advanced
      adenocarcinoma of the lung with measurable or assessable disease received
      chemotherapy with mesna, ifosfamide, carboplatin, and etoposide (MICE). Archival
      biopsies, fresh biopsies, or fine-needle aspirations were tested for the presence
      of ras gene mutations. Associations of ras mutations with clinical
      characteristics, response to chemotherapy, and survival were studied. RESULTS:
      The presence or absence of ras gene mutations could be established in 69 of 83
      patients (83%). A total of 261 courses of MICE were administered to 62
      informative patients, 16 of whom were shown to have a K-ras mutation-positive
      tumor. The frequency of mutations (26%) and the type of mutations closely matched
      the pattern we have previously reported in operable disease. Patients with a ras
      mutation in their tumor were more likely to have a close relative with lung
      cancer, but other clinical characteristics, such as pattern of metastases,
      response, and survival, were similar between the ras mutation-positive and ras
      mutation-negative groups. CONCLUSION: Patients with advanced lung adenocarcinoma
      who harbor a ras mutation may have major responses to chemotherapy and have
      similar progression-free and overall survival as patients with ras mutation
      negative tumors. K-ras mutations may represent one of several ways in which early
      tumors are enabled to metastasize to distant sites.

PMID- 8996156
TI  - Cisplatin-gemcitabine combination in advanced non-small-cell lung cancer: a phase
      II study.
AB  - PURPOSE: The nucleoside analog, gemcitabine, has shown activity as a single agent
      in the treatment of metastatic non-small-cell lung cancer (NSCLC). Its
      combination with cisplatin in preclinical models suggested synergy between the
      two drugs. The aim of the study was to evaluate the clinical efficacy and
      toxicity of the cisplatin-gemcitabine combination in advanced NSCLC. PATIENTS AND
      METHODS: Forty-eight consecutive previously untreated NSCLC patients entered the
      trial from January to June 1994. The median age was 60 years (range, 37 to 70)
      and performance status (PS) was 0 or 1; 22 patients had unresectable stage III
      disease (21 stage IIIB and one stage IIIA) and 26 had stage IV disease.
      Gemcitabine 1 g/m2 was administered weekly (days 1, 8, and 15) followed by a 1
      week rest and cisplatin 100 mg/m2 on day 2 of each 28-day cycle. Survival and
      response were determined in accordance with the intention-to-treat principle in
      all enrolled patients. RESULTS: Of 48 assessable patients, one (stage IV) had a
      complete response (CR) and 25 achieved a partial response (PR). The overall
      response rate was 54% (95% confidence interval [CI], 40% to 68%).
      Thrombocytopenia was the main side effect, with 52% of patients experiencing
      grade III to IV toxicity, which was usually short-lived and responsible for the
      omission of gemcitabine administration on day 15 in 50% of chemotherapy courses.
      The median survival time was 61.5 weeks (95% CI, 40 to 71). CONCLUSION: The
      combination of gemcitabine and cisplatin induced a high response rate in both
      stage IIIB and IV NSCLC, with modest side effects. The regimen deserves further
      careful evaluation in a phase III prospective randomized trial.

PMID- 8996155
TI  - Dose-intensive weekly chemotherapy for treatment of relapsed small-cell lung
      cancer.
AB  - PURPOSE: This study was undertaken to determine the activity and toxicity of dose
      intensive weekly chemotherapy (cisplatin, vincristine, doxorubicin, and etoposide
      [CODE] regimen) for previous treated, recurrent small-cell lung cancer (SCLC).
      PATIENTS AND METHODS: The 17 patients with relapsed SCLC entered onto the study
      were to receive intensive weekly chemotherapy with the CODE regimen. All 17
      patients had been heavily pretreated with some form of cisplatin-based
      combination chemotherapy. Six patients had received previous chemotherapy with
      CODE and one patient with cisplatin and etoposide (PE) as induction therapy. Nine
      patients had been treated with concurrent or sequential PE plus thoracic
      irradiation (TRT). The median time off chemotherapy was 6.7 months (range, 3.3 to
      72). Patients were treated with 9 weeks of the CODE regimen. Response, survival,
      and toxicity data were noted. RESULTS: All 17 patients were assessable for
      response, survival, and toxicity. Fifteen of 17 patients (88.2%) had an objective
      response, with five complete responses (CRs; 29%) and 10 partial responses (PRs;
      58.8%). The median durations of response and survival were 156 days and 245 days,
      respectively. Myelosuppression was significant, with 76% of patients developing
      grade 4 leukopenia. No treatment-related death was observed. CONCLUSION: The CODE
      regimen is highly active in the treatment of relapsed SCLC with an encouraging
      survival outcome.

PMID- 8996157
TI  - Phase II study of irinotecan and etoposide in patients with metastatic non-small
      cell lung cancer.
AB  - PURPOSE: To determine the effects of irinotecan (CPT-11) given in combination
      with etoposide (VP-16) in metastatic non-small-cell lung cancer (NSCLC), to
      evaluate response and survival rates, and to determine the qualitative and
      quantitative toxicities of the combination chemotherapy. PATIENTS AND METHODS:
      Sixty-one metastatic NSCLC patients received concurrent administration of CPT-11
      and VP-16 for 3 days with recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) support. RESULTS: Fifty-nine patients were assessable for response and
      all 61 patients were assessable for toxicity and survival. Fifty-six patients
      were treated with two or more courses of chemotherapy. Thirteen patients achieved
      a partial response (PR), 36 showed no change (NC), and 10 showed progressive
      disease (PD). The overall response rate was 21.3% (95% confidence interval, 12.9%
      to 33.1%). The median duration of PRs was 141 days (range, 62 to 299). Of the
      hematologic toxicities, 14 (23%) and 24 (39%) patients experienced grade 3 or 4
      leukopenia and neutropenia, respectively. The toxicities were feasible. Treatment
      related death occurred in one patient who suffered hypovolemic shock induced by
      hematemesis. The median survival time was 10.0 months and the 1-year survival
      rate was 36.1%. CONCLUSION: Combination chemotherapy with concurrent
      administration of CPT-11 and VP-16 with rhG-CSF support was only modestly
      effective against metastatic NSCLC, with feasible toxicities of moderate diarrhea
      and pulmonary toxicity. The results were equivalent to those expected with either
      cisplatin-based chemotherapy or with CPT-11 alone.

PMID- 8996158
TI  - Maximum-tolerated dose defined for single-agent gemcitabine: a phase I dose
      escalation study in chemotherapy-naive patients with advanced non-small-cell lung
      cancer.
AB  - PURPOSE: We conducted a phase I trial of the novel nucleoside analog,
      gemcitabine, in chemotherapy-naive patients with advanced non-small-cell lung
      cancer (NSCLC) to determine the maximum-tolerated dose and efficacy in this
      population. PATIENT AND METHODS: Eligibility requirements included stage III or
      IV NSCLC, performance status < or = 1, and no prior chemotherapy. Gemcitabine was
      administered as a 30-minute intravenous infusion weekly for 3 weeks every 4
      weeks. We enrolled patients at doses that ranged from 1,000 to 2,800 mg/m2/wk
      (three patients per cohort). Responses were assessed after every two courses (8
      weeks). RESULTS: We treated 33 chemotherapy-naive patients with stage III (n = 5)
      or IV (n = 28) NSCLC. Most had performance status 1, and 67% had adenocarcinoma.
      Eight of 32 assessable patients (25%) achieved a partial response. The projected
      median survival duration (all patients) is 49 weeks. The maximum-tolerated dose
      was 2,200 mg/m2/wk for 3 weeks every 4 weeks; dose-limiting toxicity was
      myelosuppression and reversible transaminase elevation. Other side effects were
      consistently mild. The maximum dose-intensity achieved with the first two cycles
      was 2,362 mg/m2/wk for 3 weeks every 4 weeks, which is a feasible phase II
      starting dose. CONCLUSION: This study estimates a phase II starting dose of
      gemcitabine in chemotherapy-naive patients to be 2,400 mg/m2/wk for 3 consecutive
      weeks every 4 weeks; this is much higher than that previously reported in heavily
      pretreated patients. Twenty-five percent of patients with advanced NSCLC achieved
      a partial response to gemcitabine. This significant activity in conjunction with
      a very favorable toxicity profile supports the further evaluation of gemcitabine
      in combination with other active agents.

PMID- 8996160
TI  - Trading treatment toxicity for survival in locally advanced non-small cell lung
      cancer.
AB  - PURPOSE: To determine how patients weigh potential survival benefits against the
      potential toxicity of different treatment strategies for locally advanced non
      small cell lung cancer (NSCLC). Specifically, we were interested in what
      improvement in survival probability patients would want to have before accepting
      more toxic therapy. PATIENTS AND METHODS: Fifty-six outpatients who had
      experienced lung cancer (n = 22) or prostate cancer (n = 34), and 20 clinic
      nurses and radiation therapy technologists participated. A treatment trade-off
      interview was conducted with each participant that compared low-dose versus high
      dose radiotherapy and high-dose radiotherapy versus combination chemo
      radiotherapy. Preferences for treatments were assessed by systematically
      increasing the hypothetical survival advantage of the more toxic treatment until
      the person reached his or her threshold for choosing the more toxic treatment.
      RESULTS: A wide range of thresholds was observed for both groups. The
      distributions of survival advantage thresholds for lung cancer and prostate
      cancer patients were not significantly different but were generally lower
      thresholds than those declared by staff. If the 3-year survival advantage was
      10%, 60% of patients and 15% of staff would consider combination therapy over
      high-dose radiotherapy. Within patients, apparent willingness to consider more
      toxic treatments was not significantly related to age, sex, education, or
      preferred role in decision making. The treatment trade-off method had good test
      retest reliability. CONCLUSION: There is great interindividual variability in
      willingness to accept aggressive treatments for locally advanced NSCLC. When
      choosing NSCLC treatment, each patient should be provided with comprehensive
      information about the options so that he or she may express his or her
      preferences should he or she wish to participate in the decision.

PMID- 8996159
TI  - Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose
      sequencing study in patients with non-small-cell lung cancer. The European Cancer
      Centre.
AB  - PURPOSE: To investigate the pharmacokinetics and pharmacodynamics of paclitaxel
      (P) and carboplatin (C) in a sequence-finding and dose-escalating study in
      untreated non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS:
      Fifty-five chemotherapy-naive patients with NSCLC were entered onto the
      pharmacokinetic part of a large phase I trial in which P was administered as a 3
      hour infusion at dosages of 100 to 250 mg/m2, and C over 30 minutes at dosages of
      300 to 400 mg/m2. Patients were randomized for the sequence of administration,
      first C followed by P or vice versa. Each patient received the alternate sequence
      during the second and subsequent courses. RESULTS: The most important hematologic
      toxicity encountered-was neutropenia. Hematologic toxicity was not dependent on
      the sequence in which P and C were administered, but there was cumulative
      neutropenia. Nonhematologic toxicities consisted mainly of vomiting, myalgia, and
      arthralgia. No sequence-dependent pharmacokinetic interactions for the P area
      under the concentration-time curve (P-AUC), maximal plasma concentration (P
      Cmax), or time above a threshold concentration of 0.1 mumol/L (P-T > or = 0.1
      mumol/L) were observed. However, there was a significant difference for the
      metabolite 6 alpha-hydroxypaclitaxel AUC (6OHP-AUC). Higher 6OHP-AUCs were
      observed when C was administered before P. The mean plasma ultrafiltrate AUC of C
      (CpUF-AUC) at the dosage of 300 mg/m2 for the sequence C-->P was 3.52 mg/mL.min
      (range, 1.94 to 5.83) and 3.62 mg/mL.min for the sequence P-->C (range, 1.91 to
      5.01), which is not significantly different (P = .55). Of 45 assessable patients,
      there were five major responders (three complete responders and two partial
      responders). Four of five responses occurred at dosages above dose level 4 (P 175
      mg/m2 + C 300 mg/m2). The median survival duration was best correlated with the P
      dose (4.8 months for doses < 175 mg/m2 v 7.9 months for doses > or = 175 mg/m2, P
      = .07; P-T > or = 0.1 mumol/L, 4.8 months for < 15 hours v 8.2 months for > or =
      15 hours, P = .06). CONCLUSION: There was no pharmacokinetic-sequence interaction
      between C and P in this study. A clear dose-response relation with respect to
      response rate and survival was observed. The pharmacokinetic parameter P-T > or =
      0.1 mumol/L was related to improved survival in this study.

PMID- 8996161
TI  - Phase I study of direct gene transfer of an allogeneic histocompatibility
      antigen, HLA-B7, in patients with metastatic melanoma.
AB  - PURPOSE: To determine the safety, toxicity, and efficacy of direct intratumoral
      injection of an allogeneic major histocompatibility complex (MHC) class I gene,
      HLA-B7, in a cationic lipid vector (Allovectin-7; Vical Inc, San Diego, CA) in
      patients with metastatic melanoma. PATIENTS AND METHODS: Seventeen HLA-B7
      negative patients were treated with intralesional injection of Allovectin-7.
      Twelve patients received a single intralesional injection containing 10
      micrograms (four patients), 50 micrograms (five patients), or 250 micrograms
      (three patients) of plasmid DNA. Five patients received two or three injections
      of 10 micrograms DNA to a single tumor site at 2-week intervals. Tumor biopsies
      pretherapy and 2 and 4 weeks after gene injection were obtained to determine
      expression of the plasmid by polymerase chain reaction (PCR), reverse
      transcriptase (RT)-PCR, flow cytometry, and immunohistochemistry. RESULTS:
      Toxicities were related to technical aspects of the injections or biopsies. These
      included pain, hemorrhage, pneumothorax, and hypotension. Two patients were
      hospitalized overnight for observation. Seven patients (50%) had tumor responses
      insofar as the injected nodule decreased > or = 25% by radiologic or physical
      examination. One patient with a single site of disease achieved a complete
      remission. Ninety-three percent of the patients' post-gene therapy biopsies
      contained HLA-B7 plasmid DNA, mRNA, or protein. CONCLUSION: Intratumoral
      injection of the allogeneic histocompatibility gene, HLA-B7, in a lipid vector
      can be performed safely at plasmid DNA doses < or = 250 micrograms. The safety
      profile and biologic activity of this therapy warrants further studies to define
      the mechanism of action, predictors of response, and antitumor efficacy of this
      approach.

PMID- 8996162
TI  - Comparative study of the National Cancer Institute and French Federation of
      Cancer Centers Sarcoma Group grading systems in a population of 410 adult
      patients with soft tissue sarcoma.
AB  - PURPOSE: Several histologic grading systems have been validated in soft tissue
      sarcomas (STS), but no system is currently accepted worldwide. The National
      Cancer Institute (NCI) and French Federation of Cancer Centers Sarcoma Group
      (FNCLCC) systems were examined comparatively in the same population of patients
      with STS to determine which system is the best prognosticator with regard to
      metastasis development and tumor mortality. PATIENTS AND METHODS: Four hundred
      ten adult patients with nonmetastatic STS were examined. Histologic grade was
      established according to the NCI and FNCLCC systems in each case. The prognostic
      value of both systems was examined using univariate and multivariate (Cox's
      model) analyses, and special attention was devoted to tumors with discordant
      grades. RESULTS: In univariate analysis, both the NCI and FNCLCC systems were of
      prognostic value to predict metastasis development and tumor mortality. In
      multivariate analysis, high-grade tumors, irrespective of the system used, size >
      or = 10 cm, and deep location were found to be independent prognostic factors for
      the advent of metastases. Tumor grade had a higher predictive value than size or
      depth, and higher prognostic weight was assigned to the FNCLCC grading system in
      Cox models. Grade discrepancies were observed in 34.6% of the cases. An increased
      number of grade 3 STS, a reduced number of grade 2 STS, and a better correlation
      with overall and metastasis-free survival within subpopulations with discordant
      grades were observed in favor of the FNCLCC system. CONCLUSION: The FNCLCC system
      showed slightly increased ability to predict distant metastasis development and
      tumor mortality. The use of this system to evaluate STS aggressiveness might be
      favored.

PMID- 8996163
TI  - Effect of chemotherapy on survival of craniofacial osteosarcoma: a systematic
      review of 201 patients.
AB  - PURPOSE: To evaluate the possible value of chemotherapy in the treatment of
      craniofacial osteosarcoma (CFOS). DESIGN: In a systematic review, data of 201
      patients (age, 36.6 +/- 19.0 years [mean +/- SD]) from 20 uncontrolled series on
      CFOS indexed in Medline and Excerpta Medica between 1974 and 1994 were pooled;
      180 patients had undergone surgery. Various chemotherapy regimens had been given
      to 71 patients. Radiotherapy was used in 69 patients. All patients had data for
      overall survival, and 182 had data for disease-free survival analysis. Cumulative
      survival distributions were estimated by the product-limit method, and a multiple
      regression analysis was performed. RESULTS: Patients' overall and disease-free
      survival rates were significantly improved by treatment with chemotherapy. This
      was confirmed for patients with complete surgical removal, as well as for those
      with incomplete removal of tumor. In a proportional hazards model, complete
      surgical removal and chemotherapy were independent significant factors for
      overall and disease-free survival. The effect of radiotherapy was insignificant.
      No prognostic factors could be identified among age groups, sex, and subsites.
      CONCLUSION: Evidence exists that chemotherapy improves survival in CFOS. We
      advocate the adoption of the chemotherapy protocols used for OS of the long bones
      for CFOS.

PMID- 8996165
TI  - Second-line hormonal therapy for advanced prostate cancer: a shifting paradigm.
AB  - PURPOSE: To discuss the evolution of new concepts in the Use of second-line
      hormonal therapy for patients with progressive prostate cancer despite androgen
      deprivation. DESIGN: Pertinent contemporary prostate-specific antigen (PSA)-based
      reports of the utility of secondary hormonal maneuvers after treatment with
      combined androgen blockade (CAB) were reviewed. RESULTS: The use of PSA as an end
      point in hormonerefractory prostate cancer (HRPC) trials is more widely accepted,
      but still remains somewhat controversial. Using PSA as an end point, it is clear
      that a variety of secondary hormonal maneuvers can result in responses.
      Antiandrogen withdrawal is efficacious in approximately 20% of patients and can
      be observed with a variety of antiandrogens, including flutamide, bicalutamide,
      and megestrol acetate. A variety of regimens, including megestrol, bicalutamide,
      glucocorticoids, aminoglutethimide, and ketoconazole, retain activity (14% to 75%
      PSA response proportion) even in patients who have failed to respond to CAB and
      flutamide withdrawal. CONCLUSION: Once CAB (suppression of gonadal and adrenal
      androgen) is undertaken, further hormonal maneuvers remain efficacious in some
      patients with progressive prostate cancer. Antiandrogen withdrawal is now a
      mandatory maneuver before proceeding to other regimens. It is clear that certain
      patients will continue to respond to hormonal maneuvers even after antiandrogen
      withdrawal. An understanding of the molecular basis of these responses may result
      in the development of a more targeted therapy in the future.

PMID- 8996164
TI  - Fluorouracil in colorectal cancer--a tale of two drugs: implications for
      biochemical modulation.
AB  - PURPOSE: To determine if fluorouracil (FUra) has different mechanisms of action
      as a function of the dose schedule used. DESIGN: The preclinical and clinical
      literature relating toxicity and antitumor effects of FUra as a function of its
      dose schedule, with and without modulating agents, was reviewed. RESULTS: The
      data support the hypothesis that FUra may be considered to be two different
      drugs, depending on its dose schedule (bolus v continuous infusion [CI]).
      CONCLUSION: These results suggest that additional therapeutic benefit may be
      obtained from FUra regimens by (1) appropriate schedule-dependent modulation, (2)
      the sequential or alternating use of cycles of bolus followed by cycles of CI
      FUra appropriately modulated, or (3) hybrid regimens, ie, those that contain both
      pulse and CI schedules.

PMID- 8996166
TI  - Thymidylate synthase inhibitors in cancer therapy: direct and indirect
      inhibitors.
AB  - PURPOSE AND METHODS: Although fluoropyrimidines, in particular, fluorouracil (5
      FU) and fluorodeoxyuridine (FdUrd), are active alone and in combination with
      other agents in a variety of human malignancies, therapeutic selectivity,
      resistance, and efficacy have been a major limitation in cancer therapy.
      Preclinical and clinical results in advanced and adjuvant colorectal cancers
      confirmed that the therapeutic efficacy of fluoropyrimidines, with thymidylate
      synthase (TS) as a primary target, can be improved significantly with leucovorin
      (LV) modulation. With the recognition that TS is an important therapeutic target,
      direct and specific inhibitors have been developed and are under intensive
      preclinical and clinical evaluation, primarily in patients with colorectal
      cancer, with demonstrable activity. The direct TS inhibitors have been shown to
      be potent, with a high level of specificity under therapeutic conditions for TS.
      This includes ZD1694, AG337, and LY231514. To date, although the therapeutic
      activity of both direct and indirect inhibitors of TS is similar, differences in
      the magnitude and profile of toxicity have been observed. A phase III comparative
      evaluation of a direct inhibitor of TS (ZD1694) with an indirect inhibitor (5
      FU/LV) has been completed and showed similar activity but reduced toxicity in
      favor of ZD1694. RESULTS: Recognition that greater than 95% of the injected dose
      of 5-FU is rapidly inactivated by dihydropyrimidine dehydrogenase (DPD) to
      therapeutically inactive products, but with toxicity to normal tissues, led to
      the development of inhibitors of this enzyme with the aim to modify the
      therapeutic index of 5-FU. Several inhibitors in combination with 5-FU are under
      preclinical and clinical evaluation, including uracil and 5-chloro-2,4-dihydroxy
      pyridine, as modulators of 5-FU derived from its prodrug tegafur and 5
      ethynyluracil as a modulator of 5-FU. CONCLUSION: In this review, an update of
      the present status of direct and indirect inhibitors of TS is discussed, as well
      as the future prospect for new drugs alone and in combination.

PMID- 8996167
TI  - The physician and unorthodox cancer therapies. The American Society of Clinical
      Oncology.

PMID- 8996168
TI  - Pyoderma gangrenosum.

PMID- 8996169
TI  - Antisense oligonucleotides targeting p53.

PMID- 8996170
TI  - Two doses of paclitaxel and statistical analysis: try, try, try again.

PMID- 8996171
TI  - Do all germ cell tumor patients with residual masses in multiple sites require
      postchemotherapy resections?

PMID- 8996172
TI  - Chemotherapy with mitoxantrone in hormone-refractory prostate cancer.

PMID- 8996173
TI  - Prognostic factors in early-stage Hodgkin's disease.

PMID- 8996174
TI  - Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes.
AB  - We have investigated the affinity and selectivity of tamsulosin and its
      metabolites, M1, M2, M3, M4 and AM1, at the tissue and the cloned alpha-1
      adrenoceptor subtypes in the radioligand binding and the functional studies. In
      the radioligand binding studies, the compounds competed for [3H]prazosin binding
      to the rat liver and kidney alpha-1 adrenoceptors, with the rank order of potency
      tamsulosin approximately M4 > M1 > M2 approximately M3 > > AM1 with the latter
      having a negligible affinity. All compounds differentiated cloned alpha-1
      adrenoceptor subtypes with the rank order of potency of alpha-1A > or = alpha-1D
      > alpha-1B, except for M4 which had the highest affinity for the alpha-1D
      adrenoceptor. The compounds also concentration-dependently antagonized
      phenylephrine-induced contractions in the rabbit aorta and prostate. The
      resulting apparent pA2 values were very similar to those at the cloned rat alpha
      1A adrenoceptor. We conclude that most tamsulosin metabolites are high potency
      antagonists at the alpha-1 adrenoceptors and retain the alpha-1A over the alpha
      1B adrenoceptor selectivity of tamsulosin.

PMID- 8996175
TI  - Cardiovascular effects of Sar-[D-Phe8]des-Arg9-bradykinin, a metabolically
      protected agonist of B1 receptor for kinins, in the anesthetized rabbit
      pretreated with a sublethal dose of bacterial lipopolysaccharide.
AB  - We investigated the mechanism of the hypotensive effect of Sar-[D-Phe8]des-Arg9
      bradykinin (BK) in lipopolysaccharide-treated anesthetized rabbits. The study
      involved pharmacokinetic and hemodynamic measurements and tests of antagonism
      with various drugs. The rate of elimination of Sar-[D-Phe8]des-Arg9-BK from the
      rabbit plasma was slower than that of Lys-BK, a naturally occurring B1 agonist.
      The amplitude of the hypotensive effect of Sar-[D-Phe8]des-Arg9-BK was not
      affected by pretreatment with indomethacin, diclofenac, dazmegrel, NG-nitro-L
      arginine, glibenclamide, MK-886, BN-50739, atropine or propranolol, but its
      duration was shortened by indomethacin and diclofenac. Sar-[D-Phe8]des-Arg9-BK
      induced hypotension was associated with decreases of total peripheral resistance,
      cardiac output, carotid, mesenteric and femoral blood flow, transient reductions
      followed by secondary increases of vascular resistance in the carotid and femoral
      beds, reductions of central venous pressure, but no change of hematocrit. Animal
      pretreatment with diclofenac or hexamethonium abolished the secondary increases
      of carotid bed vascular resistance caused by the B1 agonist. These and other
      results suggest that peripheral vasodilation leading to a decrease of total
      peripheral resistance and a decrease of cardiac output may both contribute
      consecutively to the hypotensive effect of Sar-[D-Phe8]des-Arg9-BK in this animal
      model. Inappropriate compensatory responses to arterial hypotension,
      prostaglandin release, and slow rate of elimination of Sar-[D-Phe8]des-Arg9-BK
      from the rabbit plasma, may all be at the basis of the prolonged duration of the
      hypotension caused by the B1 agonist.

PMID- 8996176
TI  - Chronic morphine treatment of guinea pigs induces nonspecific sensitivity changes
      in the nucleus tractus solitarius in vitro.
AB  - Chronic morphine treatment results in the development of an opioid tolerance in
      guinea pig myenteric S-neurons that is nonspecific among pharmacologically
      unrelated inhibitory agonists and the concurrent development of a nonspecific
      super-sensitivity to unrelated excitatory agonists. The purpose of these studies
      was to extend this model of opioid tolerance in the guinea pig to central
      neurons, specifically to the medial nucleus tractus solitarius (mnTS), the
      primary brainstem relay for visceroceptive information. Pharmacological responses
      of the guinea pig mnTS neurons were examined in an in vitro brainstem slice
      preparation and compared between chronically morphine-treated animals and
      untreated controls. The spontaneous activity of guinea pig mnTS neurons was
      inhibited by gamma-aminobutyric acid (GABA), the GABAA-selective agonist
      muscimol, 2-chloroadenosine and clonidine and was excited by glutamate and
      elevations in extracellular potassium. Applied alone, morphine or the GABAA
      selective antagonist bicuculline inhibited and excited approximately equal
      proportions of nucleus tractus solitarius (nTS) neurons. However, when applied in
      the presence of bicuculline, morphine inhibited most neurons tested. Reduced
      inhibitory responses to four agonists, i.e., morphine, muscimol, 2
      chloroadenosine and clonidine, were observed in mnTS neurons in slices obtained
      from chronically morphine-treated animals. Increased excitation of these neurons
      by elevated extracellular potassium was observed. It is concluded that 1) guinea
      pig nTS neurons respond similarly to nTS neurons from other species in vitro, 2)
      opioids disinhibit some proportion of guinea pig nTS neurons in vitro through a
      GABAergic mechanism and 3) the development of opioid tolerance in guinea pig nTS
      neurons is qualitatively similar to that of guinea pig myenteric S-neurons.

PMID- 8996177
TI  - Effect of flow on first-pass metabolism of drugs: single pass studies on 4
      methylumbelliferone conjugation in the serially perfused rat intestine and liver
      preparations.
AB  - The vascularly perfused rat intestine and liver preparations were used to examine
      the effect of flow (8 and 10 ml/min) on the sequential metabolism of 4
      methylumbelliferone (4MU), which forms primarily the glucuronide conjugate (4MUG)
      in intestine and the sulfate conjugate (4MUS) in liver at low input
      concentrations of 4MU. In this system, a constant tracer concentration of [3H]4MU
      was delivered systemically at 8 or 10 ml/min to the perfused rat small intestine
      preparation; the portal venous outflow perfusate at 8 and 10 ml/min was collected
      at steady state, reoxygenated and in tum delivered to the perfused rat liver
      preparation from a second rat donor. The intestinal extraction ratio and
      formation of 4MUG were decreased from 0.57 +/- 0.07 to 0.49 +/- 0.06 and 42 +/- 5
      to 36 +/- 4% input rate, respectively, upon increasing the flow rate from 8 to 10
      ml/min (P < .05). These decreases were the result of the reduction in transit
      time with increasing flows. In contrast, hepatic 4MU conjugation was increased
      (from 40 +/- 7% to 48 +/- 6% input rate to intestine) upon increasing the flow
      rate from 8 and 10 ml/min (P < .05), attributed primarily to increased formation
      of the major metabolite, 4 MUS, in liver (from 35 +/- 9% to 39 +/- 9% input rate
      to intestine). The unusual observation on increased hepatic metabolite formation
      with increasing flow could be rationalized. With increased flow to the serially
      perfused organs, there was an increased supply of substrate to the liver, the
      posterior organ, because of a faster intestinal transit time. Decreased
      intestinal metabolism (formation of 4MUG) at increased flow was compensated by
      increased hepatic metabolism (formation of 4MUS), albeit attenuated because of a
      faster hepatic transit time. The proportions of total 4MU conjugates formed (4MUG
      + 4MUS) across the intestine and liver remained constant at both flow rates.
      Hence, a rather constant overall extraction ratio (0.98 +/- 0.004 and 0.97 +/-
      0.005, P > .05) existed across the two organs. The results demonstrate that the
      intestine, the anterior organ, plays a regulatory role on substrate supply to the
      posterior organ, the liver. With an increase in flow, the contribution of the
      intestine will decrease, whereas the contribution of the liver will increase in
      the overall first-pass metabolism.

PMID- 8996178
TI  - Effects of chronic morphine treatment on catecholamines content and mechanical
      response in the rat hearts.
AB  - Our investigation was aimed at elucidating if the chronic administration and
      withdrawal of a preferential mu-agonist, morphine, induce changes on the heart
      catecholaminergic neuronal activity. With this purpose the effects of morphine or
      naloxone (preferentially mu-antagonist) on noradrenaline, adrenaline or dopamine
      (DA) content and the mechanical response of the left atria were studied in
      chronically placebo- or morphine-treated rats (implanted s.c. with pellets for 7
      days). In morphine-treated rats, a challenge dose of morphine (30 mg/kg i.p.)
      increased the auricular noradrenaline, adrenaline and DA content and decreased
      dihydroxy phenyl acetic acid/DA ratio; these changes were accompanied by a
      decrease in the force of contraction in the isolated left atria. No changes were
      observed in placebo-treated rats. The administration of naloxone (1 mg/kg s.c.)
      to morphine-treated animals induced a decrease on the auricular content of
      noradrenaline, adrenaline and DA and an increase in dihydroxy phenyl acetic
      acid/DA ratio. The study of the mechanical response to naloxone in the isolated
      left atria showed an enhancement in the force of contraction in preparations from
      morphine-treated rats, whereas in the placebo-pelleted rats naloxone induced a
      decrease in this parameter. These findings demonstrate that the heart of rats
      that had received chronic morphine-treatment exhibit excitatory reactions to
      naloxone-precipitated withdrawal and suggest that the changes observed in the
      heart by the chronic administration of morphine and after naloxone precipitated
      withdrawal are mostly mediated by the catecholaminergic system.

PMID- 8996179
TI  - Modulation of ATP-sensitive and large-conductance Ca++-activated K+ channels by
      Zeneca ZD6169 in guinea pig bladder smooth muscle cells.
AB  - ZD6169, the S-enantiomer of the racemic N-(4-benzoylphenyl)-3,3,3-trifluoro-2
      hydroxy-2-methylpropionamide , was reported to possess a mechanoinhibitory effect
      on bladder detrusor smooth muscle through its ability to activate the KATP
      sensitive K+ channel (KATP). In this study, the effects of ZD6169 and its racemic
      mixture on the whole-cell KATP and large-conductance CA+2-activated K+ (BKCa)
      currents in isolated smooth muscle cells from guinea pig bladder detrusor were
      examined by the patch-clamp technique. ZD6169 produced a multiple stimulatory and
      inhibitory effect on the KATP current. With a threshold effective concentration
      of 0.5 microM, it produced a glyburide-sensitive activation that reached a
      maximum between 5 and 10 microM. ZD6169 at concentrations greater than 20 microM
      markedly inhibited KATP channel, which resulted in a bell-shaped concentration
      response relationship. Over a similar concentration range, ZD6169 caused a
      sizable stimulation of the BKCa current. All effects were readily reversible.
      Consistent with the data in whole-cell recordings, ZD6169 activated single BKCa
      channel in inside-out patches by increasing its open-state probability. Several
      lines of evidence showed that the opening of BKCa channel was Ca+2 independent.
      The activity profile of the racemic ZD6169 on KATP and BKCa channels had
      remarkable resemblance to that of ZD6169. Our results indicate that ZD6169 exerts
      diverse effects on multiple types of K+ channels. A combination of the absence of
      KATP channel activation and the presence of BKCa channel stimulation by ZD6169 at
      higher concentrations may be responsible, in part, for its reported weaker
      cardiovascular side effects than cromakalim.

PMID- 8996180
TI  - Effects of strychnine-insensitive glycine receptor ligands in rats discriminating
      dizocilpine or phencyclidine from saline.
AB  - Several pharmacologically distinct sites are known to modulate the N-methyl-D
      aspartate (NMDA) receptor/ion complex, including a site within the ion channel
      which binds uncompetitive antagonists like phencyclidine (PCP) or dizocilpine.
      Glycine acts as a co-agonist for activation of the NMDA receptor complex through
      a strychnine-insensitive receptor, which is a potential target for novel
      therapeutic agents (e.g., anticonvulsants, antidepressants). We evaluated the
      behavioral effects of glycine receptor ligands in rats trained to discriminate
      either dizocilpine or PCP from saline, to predict whether glycine receptor
      ligands might induce undesirable PCP-like subjective effects in humans.
      Dizocilpine ([+]-MK-801), (-)-MK-801 and PCP produced dose-dependent substitution
      in these rats with potencies in accord with NMDA receptor affinity. Pentobarbital
      and drugs acting at other sites of the NMDA receptor, including competitive
      antagonists (NPC 12626 and LY 274614) and the polyamine antagonist, ifenprodil,
      did not substitute for either dizocilpine or PCP. In contrast to the
      uncompetitive antagonists like PCP, none of the strychnine-insensitive glycine
      receptor ligands substituted. Neither the full agonist, glycine; the partial
      agonists, 1-amino-1-cyclopropanecarboxylic acid, D-cycloserine or (+)-3-amino-1
      hydroxypyrrolid-2-one; nor the antagonists, 7-chloro and 5,7-dichlorokynurenic
      acid, mimicked the discriminative stimulus effects of dizocilpine or PCP.
      Further, co-administration of 1-amino-1-cyclopropanecarboxylic acid did not
      significantly enhance the discriminative stimulus effects of dizocilpine.
      Intracerebroventricular administration of D-serine, a selective agonist of the
      strychnine-insensitive glycine receptor, neither mimicked nor blocked the
      discriminative stimulus effects of PCP. These data suggest that functional
      antagonists of the strychnine-insensitive glycine receptor may be devoid of the
      subjective side effects characteristic of NMDA channel ligands.

PMID- 8996181
TI  - Protection from T cell-mediated murine liver failure by phosphodiesterase
      inhibitors.
AB  - Injection of the T cell mitogens concanavalin A (Con A) into nonsensitized or of
      staphylococcal enterotoxin B (SEB) into D-galactosamine (GalN)-sensitized mice is
      known to cause fulminant liver failure via a cytokine response syndrome with
      tumor necrosis factor-alpha (TNF) as the plvotal mediator. We examined in vivo
      whether the phosphodiesterase (PDE) inhibitors motapizone (PDE3-selective) and
      rolipram (PDE4-selective) affected cytokine release and hepatic injury after T
      cell activation. Both motapizone as well as rolipram dose-dependently (0.1-10
      mg/kg) attenuated the systemic release of TNF and interferon-gamma as initiated
      by injection of Con A (25 mg/kg) or SEB (2 mg/kg). Although interleukin-4
      production was not affected by motapizone or decreased by rolipram, circulating
      levels of interleukin-10, however, were significantly increased in PDE inhibitor
      treated mice compared with controls. Associated with the suppression of the
      central mediator TNF, motapizone and rolipram protected mice from liver injury in
      the Con A as well as in the SEB model. Moreover, the combined administration of
      motapizone plus rolipram at doses which were ineffective when given alone
      completely protected mice from GalN/SEB toxicity. These data demonstrate that PDE
      inhibitors effectively attenuate an inflammatory T cell response in vivo and
      strongly suggest a therapeutic potential as anti-inflammatory drugs in T cell
      related disorders. We conclude that cAMP-elevating drugs shift the balance of T
      cell-derived cytokines from a proinflammatory to an enhanced anti-inflammatory
      factor release, thus protecting mice from TNF-mediated hepatic failure.

PMID- 8996182
TI  - Inhibition of lipopolysaccharide-induced nitric oxide and cytokine production by
      ultralow concentrations of dynorphins in mixed glia cultures.
AB  - Dynorphins (dyn) are a major class of endogenous opioid peptides that modulate
      the functions of immune cells. However, the effects of dyn on the immune
      functions of glial cells in the central nervous system (CNS) have not been well
      characterized. Because nitric oxide (NO) and the proinflammatory cytokine tumor
      necrosis factor-alpha (TNF-alpha) produced by glial cells are involved in various
      physiopathological conditions in the CNS, this study examined the effects of dyn
      on the production of NO and TNF-alpha from mouse glial cells treated with
      lipopolysaccharide (LPS). LPS induced a concentration-dependent increase in the
      production of NO or TNF-alpha from the mouse primary mixed glia cultures.
      Ultralow concentrations (10(-16)-10(-12) M) of dynorphin (dyn) A-(1-8)
      significantly inhibited the LPS-induced production of NO or TNF-alpha. The
      inhibitory effects of dyn A-(1-8) were not blocked by nor-binaltorphimine, a
      selective kappa opioid receptor antagonist. U50-488H, a selective kappa opioid
      receptor agonist, did not affect the LPS-induced production of NO or TNF-alpha.
      Ultralow concentrations (10(-16)-10(-12) M) of des-[Tyr1]-dyn A-(2-17), a
      nonopioid analog that does not bind to kappa opioid receptors, exhibited the same
      inhibitory effects as dyn A-(1-17) and dyn A-(1-8). These results suggest that
      dyn modulate the immune functions of microglia and/or astrocytes in the brain and
      these modulatory effects of dyn are not mediated by classical kappa opioid
      receptors.

PMID- 8996183
TI  - Effect of GK-128 [2-[(2-methylimidazol-1-yl)methyl]-benzo[f]thiochromen-1-one
      monohydrochloride hemihydrate], a selective 5-hydroxytryptamine3 receptor
      antagonist, on colonic function in rats.
AB  - We investigated the effects of various selective 5-hydroxytryptamine (5-HT)3
      receptor antagonists, including GK-128 [2-[(2-methylimidazol-1
      yl)methyl]benzo[f]thiochromen-1-one monohydrochloride hemihydrate], on colonic
      function. In conscious rats, 5-HT and a 5-HT3 receptor agonist, 2-methyl-5-HT,
      dose-dependently increased fecal pellet output, but another 5-HT3 receptor
      agonist, m-chlorophenylbiguanide, did not affect output. The selective 5-HT3
      receptor antagonists GK-128, granisetron, ramosetron, azasetron and ondansetron
      depressed the increase in fecal pellet output caused by 2-methyl-5-HT and by wrap
      restraint stress. However, the rank order of potency of antagonists in the two
      defecation models was not consistent with that for the von Bezold-Jarisch reflex.
      Although granisetron and ramosetron dose-dependently reduced the spontaneous
      excretion of fecal pellets, GK-128 did not affect it. These results suggest that
      GK-128 may be used for the treatment of stress-induced gastrointestinal
      dysfunction. Furthermore, the present results suggest that the 5-HT3 receptor
      involved in colonic motility may be different from the classically defined 5-HT3
      receptor and/or that the regulation of colonic motility mediated by 5-HT3
      receptors during stress may be different from normal physiological conditions.

PMID- 8996184
TI  - Psychopharmacological profile of amisulpride: an antipsychotic drug with
      presynaptic D2/D3 dopamine receptor antagonist activity and limbic selectivity.
AB  - Amisulpride, a benzamide derivative, is an antipsychotic drug with a
      pharmacological profile distinct from that of classical neuroleptics such as
      haloperidol and from that of another benzamide, remoxipride. In mice, amisulpride
      antagonized hypothermia induced by apomorphine, quinpirole or (+/-) 7-hydroxy-2
      (di-n-propylamino)-tetralin, an effect involving D2/D3 receptors, at similar
      doses (ED50 approximately 2 mg/kg i.p.), which were much lower than doses that
      blocked apomorphine-induced climbing, an effect involving postsynaptic D2 and D1
      receptor activation (ED50 = 21 mg/kg i.p.). Much higher doses (ED50 = 54 mg/kg
      i.p.) of amisulpride were needed to block grooming behavior observed after a
      short period in water, a D1 receptor-mediated behavior. In rats, amisulpride
      preferentially inhibited effects produced by low doses of apomorphine
      (hypomotility and yawning), related to stimulation of presynaptic D2/D3 dopamine
      autoreceptors (ED50 = 0.3 and 0.19 mg/kg i.p.). By contrast, amisulpride
      antagonized apomorphine-induced hypermotility, a postsynaptic dopamine receptor
      mediated effect, at a much higher dose (ED50 = 30 mg/kg i.p.). Amisulpride (100
      mg/kg i.p.) only partially inhibited apomorphine-induced stereotypies (gnawing)
      and had no effect on stereotypies induced by d-amphetamine. However, d
      amphetamine-induced hyperactivity was antagonized by doses of amisulpride as low
      as 3 mg/kg i.p., which may indicate selectivity of this drug for limbic
      dopaminergic mechanisms. In addition, in contrast to haloperidol or remoxipride,
      which produced catalepsy at doses 2 or 3 times higher than those that antagonized
      stereotypies induced by apomorphine, amisulpride did not induce catalepsy up to a
      dose of 100 mg/kg i.p., which occupies 80% of striatal D2 receptors. This
      pharmacological profile of amisulpride, characterized by a preferential blockade
      of effects involving presynaptic mechanisms and limbic structures, may explain
      the clinical efficacy of this drug against both negative and positive symptoms of
      schizophrenia and its low propensity to produce extrapyramidal side effects.

PMID- 8996185
TI  - Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor
      antagonist with both presynaptic and limbic selectivity.
AB  - The benzamide derivative amisulpride shows a unique therapeutic profile being
      antipsychotic, at high doses, and disinhibitory, at low doses, while giving rise
      to only a low incidence of extrapyramidal side effects. In vitro, amisulpride has
      high affinity and selectivity for the human dopamine D2 (Ki = 2.8 nM) and D3 (Ki
      = 3.2 nM) receptors. Amisulpride shows antagonist properties toward D3 and both
      pre- and postsynaptic D2-like dopamine receptors of the rat striatum or nucleus
      accumbens in vitro. At low doses (< or = 10 mg/kg) amisulpride preferentially
      blocks presynaptic dopamine autoreceptors that control dopamine synthesis and
      release in the rat, whereas at higher doses (40-80 mg/kg) postsynaptic dopamine
      D2 receptor occupancy and antagonism is apparent. In contrast, haloperidol is
      active in all of these paradigms within the same dose range. Amisulpride
      preferentially inhibits in vivo binding of the D2/D3 antagonist [3H]raclopride to
      the limbic system (ID50 = 17 mg/kg) in comparison to the striatum (ID50 = 44
      mg/kg) of the rat, increases striatal and limbic tissue 3,4-dihydroxyphenylacetic
      acid levels with similar potency and efficacy, and preferentially increases
      extracellular 3,4-dihydroxyphenylacetic acid levels in the nucleus accumbens when
      compared to the striatum. Haloperidol shows similar potency for the displacement
      of in vivo [3H]raclopride binding in striatal and limbic regions and
      preferentially increases striatal tissue 3,4-dihydroxyphenylacetic acid levels.
      The present data characterize amisulpride as a specific dopamine receptor
      antagonist with high and similar affinity for the dopamine D2 and D3 receptor. In
      vivo, it displays a degree of limbic selectivity and a preferential effect, at
      low doses, on dopamine D2/D3 autoreceptors. This atypical profile may explain the
      therapeutic efficacy of amisulpride in the treatment of both positive and
      negative symptoms of schizophrenia.

PMID- 8996186
TI  - Renal and cerebrospinal fluid formation pharmacology of a high molecular weight
      carbonic anhydrase inhibitor.
AB  - To achieve selective inhibition of cytosolic and membrane-bound carbonic
      anhydrase (CA II and CA IV, respectively), we synthesized a polymer of molecular
      weight 3500 from polyoxyethylene bis acetic acid and aminobenzolamide. The new
      compound, designated F (for Florida) 3500, is stable, water soluble and nontoxic.
      It is excreted largely unchanged by glomerular filtration. The Ki at 37 degrees C
      against CA II is 0.14 microM and against CA IV 4.0 microM, some 20 times more
      than the parent aminobenzolamide and about three times more than acetazolamide or
      methazolamide. F 3500 does not penetrate red cells and is confined to
      extracellular fluid. Relations of dose to renal HCO3-excretion was studied by
      i.v. injection into rats. Peak effect was reached with 100 mg/kg, eliciting 40 mM
      HCO3- in urine; this is taken to be the effect of inhibiting CA IV. This compares
      to a peak of 103 mM HCO3- after 3 mg/kg aminobenzolamide, which agrees with
      previous data on other low molecular weight sulfonamides and defines the effect
      on CA II and CA IV. We conclude that both isozymes are necessary for normal full
      renal reabsorption of HCO3-. We studied the effect of perfusing F 3500 (100-4000
      microM) through the ventriculo-cisternal system of rats on cerebrospinal fluid
      (CSF) formation. F 3500 was also given intravenously at 100 mg/kg. CSF formation
      was unaffected. Low MW sulfonamides by either route lowered CSF formation 30 to
      50%. It appears either that membrane-bound enzyme (CA IV) is not accessible from
      the CSF or blood side or that it plays little or no role in CSF formation.

PMID- 8996187
TI  - Decreases in evoked overflow of dopamine in rat striatum after neurotoxic doses
      of methamphetamine.
AB  - The repeated administration of methamphetamine (METH) can result in long-lasting
      decreases in dopamine (DA) levels, tyrosine hydroxylase activity and DA uptake
      sites in the striatum. However, whether these changes lead to functional
      alterations in the dynamics of DA release and uptake has not been extensively
      examined. The present study used in vivo electrochemistry and microdialysis to
      examine potassium- and amphetamine-evoked release of DA in the striatum and
      nucleus accumbens (NAc) of METH-treated rats. Male Fischer-344 rats were
      administered METH (5 mg/kg s.c.) or saline four times in 1 day, at 2-hr
      intervals. One week later the animals were anesthetized with urethane and
      prepared for in vivo electrochemical recordings. The METH treatment resulted in
      dramatic decreases in potassium-evoked release of DA and in the rate of DA
      clearance in the striatum, whereas the NAc was not significantly affected. In
      vivo microdialysis studies demonstrated significant decreases in basal DA levels
      and in potassium- and amphetamine-evoked overflow of DA in the striatum of METH
      treated animals. Basal and evoked DA levels in the NAc were not altered. Post
      mortem levels of tissue DA were decreased by 41 to 67% in the striatum and 25 to
      31% in the NAc. These results indicate that the striatum is more sensitive than
      the NAc to the neurotoxic effects of METH, both in measures of functional
      dynamics of DA signaling and in tissue levels of DA. It remains to be determined
      whether these functional changes in DA release and uptake are permanent or tend
      to recover over time.

PMID- 8996188
TI  - Rupatadine, a new potent, orally active dual antagonist of histamine and platelet
      activating factor (PAF).
AB  - Rupatadine (UR-12592, 8-chloro-6, 11-dihydro-11-[1-[(5-methyl3-pyridinyl) methyl]
      4-piperidinylidene]-5H-benzo[5,6]-cyclohepta[1,2b]pyridine ) is a novel compound
      that inhibits both platelet-activating factor (PAF) and histamine (H1) effects
      through its interaction with specific receptors (Ki(app) values against [3H]WEB
      2086 binding to rabbit platelet membranes and [3H]-pyrilamine binding to guinea
      pig cerebellum membranes were 0.55 and 0.10 microM, respectively). Rupatadine
      competitively inhibited histamine-induced guinea pig ileum contraction (pA2 =
      9.29 +/- 0.06) without affecting contraction induced by ACh, serotonin or
      leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet
      aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 +/- 0.08) and in human
      platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or
      arachidonic acid-induced platelet aggregation. Rupatadine blocked histamine- and
      PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44
      mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and
      9.6 micrograms/kg i.v.). Moreover, it potently inhibited PAF-induced mortality in
      mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin
      induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.). Rupatadine's
      duration of action was long, as assessed by the histamine- and PAF-induced
      increase in vascular permeability test in dogs (42 and 34% inhibition at 26 h
      after 1 mg/kg p.o.). Rupatadine at a dose of 100 mg/kg p.o. neither modified
      spontaneous motor activity nor prolonged barbiturate-sleeping time in mice, which
      indicates a lack of sedative effects. Overall, rupatadine combines histamine and
      PAF antagonist activities in vivo with high potency, the antihistamine properties
      being similar to or higher than those of loratadine, whereas rupatadine's PAF
      antagonist effects were near those of WEB-2066. Rupatadine is therefore a good
      candidate for further development in the treatment of allergic and inflammatory
      conditions in which both PAF and histamine are implicated.

PMID- 8996189
TI  - Cloning, expression and pharmacological characterization of rabbit adenosine A1
      and A3 receptors.
AB  - The role of adenosine A1 and A3 receptors in mediating cardioprotection has been
      studied predominantly in rabbits, yet the pharmacological characteristics of
      rabbit adenosine A1 and A3 receptor subtypes are unknown. Thus, the rabbit
      adenosine A3 receptor was cloned and expressed, and its pharmacology was compared
      with that of cloned adenosine A1 receptors. Stable transfection of rabbit A1 or
      A3 cDNAs in Chinese hamster ovary-K1 cells resulted in high levels of expression
      of each of the receptors, as demonstrated by high-affinity binding of the A1/A3
      adenosine receptor agonist N6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA).
      For both receptors, binding of 125I-ABA was inhibited by the GTP analog 5'
      guanylimidodiphosphate, and forskolin-stimulated cyclic AMP accumulation was
      inhibited by the adenosine receptor agonist (R)-phenylisopropyladenosine. The
      rank orders of potency of adenosine receptor agonists for inhibition of 125I-ABA
      binding were as follows: rabbit A1, N6-cyclopentyladenosine = (R)
      phenylisopropyladenosine > N-ethylcarboxamidoadenosine > or = I-ABA > or = N6-2
      (4-aminophenyl) ethyladenosine > > N6-(3-iodobenzyl)adenosine-5'-N
      methyluronamide > N6-(4-amino-3-benzyl)adenosine; rabbit A3, N6-(3
      iodobenzyl)adenosine-5'-N-methyluronamide > or = I-ABA > > N
      ethylcarboxamidoadenosine > N6-2-(4-aminophenyl) ethyladenosine = N6
      cyclopentyladenosine = (R)-phenylisopropyladenosine > N6-(4-amino-3
      benzyl)adenosine. The adenosine receptor antagonist rank orders were as follow:
      rabbit A1, 8-cyclopentyl-1,3-dipropylxanthine > 1,3- dipropyl-8-(4
      acrylate)phenylxanthine > or = xanthine amine congener > > 8-(p
      sulfophenyl)theophylline; rabbit A3, xanthine amine congener > 1,3-dipropyl-8-(4
      acrylate)phenylxanthine > or = 8-cyclopentyl-1,3-dipropylxanthine > > 8-(p
      sulfophenyl)theophylline. These observations confirm the identity of the
      expressed proteins as A1 and A3 receptors. The results will facilitate further in
      depth studies of the roles of A1 and A3 receptors in adenosine-mediated
      cardioprotection in rabbits, which can now be based on the appropriate
      recombinant rabbit A1 and A3 receptor pharmacology.

PMID- 8996190
TI  - Chronic cocaine enhances gamma-aminobutyric acid and glutamate release by
      altering presynaptic and not postsynaptic gamma-aminobutyric acidB receptors
      within the rat dorsolateral septal nucleus.
AB  - Cocaine is a popular and sometimes deadly drug of abuse. Its mechanisms of action
      have previously not been linked with receptors localized to presynaptic sites for
      the major central nervous system amino acid transmitters gamma-aminobutyric acid
      (GABA) and glutamate. We demonstrate that, within the dorsolateral septal nucleus
      of in vitro brain slices from animals that had received cocaine chronically in
      vivo for 14 or 28, but not 7, days, control of both inhibitory (GABA) and
      excitatory (glutamate) amino acid transmission is impaired, due to the combined
      diminished effectiveness of presynaptic GABAB auto- and heteroreceptors. As a
      result, disinhibition of inhibitory and excitatory transmitters occurs, with
      enhanced transmitter release. Although the involvement of postsynaptic GABAB
      receptors has been suggested in the chronic actions of cocaine at other central
      nervous system nuclei, we do not see any change in the effectiveness of the
      postsynaptic GABAB receptors within the dorsolateral septal nucleus. Modulation
      of presynaptic GABAB receptors at central nervous system nerve terminals after
      chronic cocaine administration has not been reported previously. Our findings
      demonstrate that chronic intermittent cocaine administration for at least 14 days
      induces a persistent change in neuronal activity that involves both inhibitory
      and excitatory amino acid-mediated transmission within the dorsolateral septal
      nucleus. These results suggest that nerve terminal GABAB receptors have been
      overlooked as playing a role in either the etiology and treatment of chronic
      cocaine addiction or cocaine toxicity.

PMID- 8996191
TI  - Effect of prenatal fluoxetine (Prozac) exposure on brain serotonin neurons in
      prepubescent and adult male rat offspring.
AB  - The present study examines the consequences of prenatal fluoxetine exposure on
      brain serotonin [5-hydroxytryptamine (5-HT)] neurons in male offspring. Pregnant
      rats were administered either saline or fluoxetine (10 mg/kg s.c.) daily from
      gestational day 13 through gestational day 20. The biochemical status of brain 5
      HT neurons was assessed in prepubescent and adult offspring by measuring 1) the 5
      HT and 5-hydroxyindoleacetic acid content, 2) the density of [3H]paroxetine
      labeled 5-HT uptake sites and 3) the ability of the 5-HT-releasing drug p
      chloroamphetamine to reduce 5-HT content. Biochemical parameters were assessed in
      the frontal cortex, hypothalamus, hippocampus, striatum and midbrain. Comparative
      effects on dopamine and norepinephrine content in selected regions were also
      determined. Prenatal exposure to fluoxetine significantly reduced (-28%) 5-HT
      content in the frontal cortex of prepubescent but not adult male offspring. In
      contrast, in adult progeny prenatal fluoxetine exposure produced a significant
      decrease only in midbrain 5-HT content (-28%). In addition, p-chloroamphetamine
      markedly reduced 5-HT content in all brain regions examined, but the ability of p
      chloroamphetamine to reduce 5-HT content was significantly attenuated only in the
      midbrain of adult progeny prenatally exposed to fluoxetine. No significant
      differences were observed between control and fluoxetine-exposed progeny with
      respect to brain 5-hydroxyindoleacetic acid content, the 5-hydroxyindoleacetic
      acid/5-HT ratio or the density of 5-HT uptake sites, regardless of the brain
      region examined or the age of the offspring. These data provide additional
      evidence that prenatal exposure to fluoxetine can produce limited, rather than
      global, changes in brain 5-HT neurons in male rat offspring and that the effects
      observed are region-specific and age-dependent. The potential functional
      consequences and clinical implications of these alterations in brain 5-HT systems
      remain to be elucidated.

PMID- 8996192
TI  - Hypocholesterolemic activity of raloxifene (LY139481): pharmacological
      characterization as a selective estrogen receptor modulator.
AB  - After once-daily oral dosing in ovariectomized rats, raloxifene (LY139481)
      hydrochloride produced dose- and time-dependent reductions in serum cholesterol
      and high-density lipoprotein-cholesterol. Paired-feeding studies demonstrated
      that effects of raloxifene on serum lipids were not secondary to effects on food
      consumption. Maximal reductions in serum cholesterol occurred within 4 days of
      raloxifene administration or sooner, depending on the administered dose. The ED50
      for 50% reduction in serum cholesterol by raloxifene was 0.13 +/- 0.04 mg/kg/day
      (mean +/- S.E.M., n = 17); maximal cholesterol reduction by raloxifene (68%) was
      significantly less than that produced by estrogen (17 alpha-ethinylestradiol;
      89%) after 4 to 7 days of daily dosing. Dose-response curves for cholesterol
      lowering by raloxifene were generated in the presence of varying doses of 17
      alpha-ethinylestradiol; two-way analysis of variance revealed significant
      interactions between estrogen and raloxifene with respect to cholesterol lowering
      (P < .001). Furthermore, a high dose of raloxifene (10 mg/kg/day) prevented
      further reduction of serum cholesterol by estrogen (1-100 micrograms/kg/ day)
      beyond that produced by raloxifene alone. For a series of closely related
      structural analogs of raloxifene, log(ED50) values for cholesterol lowering were
      highly correlated with log(relative binding affinity) for the estrogen receptor
      (r = 0.93; P < .0001). Thus, cholesterol lowering by raloxifene in ovariectomized
      rats is mediated primarily via partial agonist effects at estrogen receptors.
      Taken together with previous observations in uterine tissue of estrogen
      antagonism by raloxifene in the absence of significant agonism, the present
      findings support the classification of raloxifene as a selective estrogen
      receptor modulator.

PMID- 8996193
TI  - Dual excitatory and inhibitory effect of nitric oxide on peristalsis in the
      guinea pig intestine.
AB  - The implications of the enteric neurotransmitter nitric oxide (NO) in intestinal
      peristalsis were investigated. Propulsive motility in isolated segments of the
      guinea pig ileum was triggered by intraluminal fluid infusion to distend the
      intestinal wall, and the pressure threshold for eliciting peristaltic waves was
      used to quantify facilitation (decrease in threshold) or inhibition (increase in
      threshold) of peristalsis. The NO donor sodium nitroprusside (0.1-100 microM
      serosally) caused a prompt facilitation of peristalsis, which in the presence of
      a threshold concentration of atropine (10 nM) was followed by a concentration
      related blockade of peristalsis. Further analysis showed that sodium
      nitroprusside (10 and 100 microM) first relaxed, then contracted, and finally
      relaxed the longitudinal muscle of the guinea pig isolated ileum, the contraction
      being blocked by atropine (1 microM). Inhibition of NO synthase by NG-nitro-L
      arginine methylester (100-300 microM) facilitated peristalsis, an effect that was
      reduced by L-arginine (1 mM) but left unaltered by atropine (10 nM). Blockade of
      inhibitory neuromuscular transmission by successive exposure of the ileum to
      apemin (0.5 microM) and NG-nitro-L-arginine methylester (300 microM), in this or
      reverse order, disrupted the coordinated pattern of peristalsis and caused
      irregular nonpropulsive contractions of the circular muscle. It is concluded that
      NO has a dual excitatory and inhibitory effect on intestinal motility. The
      excitatory effect involves cholinergic motor neurons, whereas the inhibitory
      effect reflects relaxation of intestinal muscle. Abolition of peristalsis by
      combined exposure to NG-nitro-L-arginine methylester and apamin attests to an
      essential role of enteric inhibitory motor neurons in the coordination of
      propulsive motility in the intestine.

PMID- 8996194
TI  - Discriminative stimulus effects of zolpidem in pentobarbital-trained subjects: I.
      Comparison with triazolam in rhesus monkeys and rats.
AB  - The present study compared the discriminative stimulus effects of the
      imidazopyridine, zolpidem, with a triazolobenzodiazepine, triazolam, in
      pentobarbital-trained rhesus monkeys and rats. Rhesus monkeys (n = 4), trained to
      discriminate pentobarbital (10 mg/kg intragastric [i.g.]) from saline under a FR
      1 discrete-trials shock avoidance procedure, were given zolpidem (0.10-30 mg/kg
      i.g.) or triazolam (0.01-0.3 mg/kg i.g.). Both zolpidem and triazolam produced
      dose-dependent increases in pentobarbital-appropriate responding that reached 80%
      or greater at the highest doses tested. Zolpidem, but not triazolam, increased
      latency to respond in a dose-dependent manner. Sprague-Dawley rats (n = 12),
      trained to discriminate pentobarbital (8.0 mg/kg i.p.) from saline under a FR 10
      schedule of food reinforcement, were given zolpidem (0.50-4.0 mg/kg i.p.; 5-, 15-
      and 45-min pretreatment) or triazolam (0.025-0.20 mg/kg i.p., 15-min
      pretreatment). Zolpidem occasioned intermediate drug-appropriate responding
      (maximum group mean = 48%) at the 5- and 15-min pretreatment times and no drug
      appropriate responding at the 45-min pretreatment time. In contrast, triazolam
      occasioned > or = 80% pentobarbital-appropriate responding at 0.10 and 0.20
      mg/kg. Both zolpidem and triazolam produced dose-dependent decreases in the rate
      of responding. The rate-decreasing effects of zolpidem were maximal at the 5-min
      pretreatment time and had dissipated after the 45-min pretreatment time. Further
      studies were conducted in rats to equate procedural variables between the monkey
      and rat studies. When the FR was reduced from 10 to 1, zolpidem occasioned 26 to
      62% pentobarbital-appropriate responding over a dose range of 1.0 to 6.0 mg/kg
      i.p. After i.g. administration, zolpidem occasioned 100% drug-appropriate
      responding at the highest dose tested (6.0 mg/kg); however, only two of seven
      rats responded. Taken together, these data raise the possibility of a species
      difference between non-human primates and rats in the pentobarbital-like
      discriminative stimulus effects of zolpidem.

PMID- 8996195
TI  - Discriminative stimulus effects of zolpidem in pentobarbital-trained subjects:
      II. Comparison with triazolam and caffeine in humans.
AB  - In the present study, four non-drug-abusing humans were trained to discriminate
      between a hypnotic dose of pentobarbital, 100 mg, and placebo. After acquiring
      the pentobarbital-placebo discrimination, a range of doses of zolpidem,
      triazolam, pentobarbital and caffeine were tested to determine whether they
      shared discriminative stimulus effects with the training dose of pentobarbital,
      Zolpidem, a rapid-onset, short-duration, quickly eliminated imidazopyridine
      hypnotic agent, was tested because its discriminative stimulus effects have been
      shown to differ from those of classic sedative/hypnotic compounds in rodents, but
      not in nonhuman primates. Triazolam and caffeine were included as positive and
      negative controls, respectively. The subject-rated and performance-impairing
      effects of zolpidem, triazolam, pentobarbital and caffeine were assessed
      concurrently. These four subjects met the discrimination criterion (> or = 80%
      correct drug identifications on four consecutive seasions) in 4 to 18 (mean =
      8.5) sessions, and the pentobarbital-placebo discrimination was well maintained
      during a test-of-novel-doses and test-of-novel-drugs phase (i.e., placebo and 100
      mg pentobarbital occasioned 0-35% [mean = 17%] and 75-100% [mean = 85%] drug
      appropriate responding, respectively). Zolpidem, triazolam and pentobarbital
      generally produced dose-related increases in pentobarbital-appropriate responding
      and sedative-like, subject-rated drug effects. Caffeine on average produced low
      levels of pentobarbital-appropriate responding, although some doses of caffeine
      produced maximal pentobarbital-appropriate responding in some subjects. Caffeine
      produced some stimulant-like (e.g., jittery, motivated, nervous and stimulated)
      subject-rated drug effects. Zolpidem and triazolam, and to a much lesser extent
      pentobarbital, but not caffeine, impaired performance. These results suggest that
      humans can acquire and maintain a pentobarbital-placebo discrimination, and this
      discrimination is pharmacologically specific. These results also suggest that
      despite the somewhat unique biochemical profile of zolpidem, its discriminative
      stimulus, subject-rated and performance-pairing effects are similar to those of
      classic sedative/hypnotic compounds like the barbiturates and benzodiazepines.
      Finally, the results observed in the present study with zolpidem, triazolam and
      caffeine demonstrate that the discriminative stimulus effects of drugs observed
      with nonhuman primates can be systematically replicated in humans.

PMID- 8996196
TI  - M2 muscarinic receptor inhibition of agonist-induced cyclic adenosine
      monophosphate accumulation and relaxation in the guinea pig ileum.
AB  - The purpose of this study was to characterize the role of M2 muscarinic receptors
      in inhibiting relaxant effects of drugs that stimulate cyclic AMP (cAMP)
      accumulation in the guinea pig ileum. We investigated the ability of oxotremorine
      M (oxo-M) to inhibit cAMP accumulation in the presence of agonists that stimulate
      adenylyl cyclase in other cells and tissues. Appreciable stimulation of cAMP (>
      50% over basal levels) was achieved with forskolin and maximally effective
      concentrations of isoproterenol, cicaprost, prostaglandin E1, prostaglandin E2
      and prostaglandin I2, with the stimulation over basal levels of cAMP being 14.9-,
      2.51-, 2.45-, 2.27-, 2.28- and 1.52-fold, respectively. Moderate or no cAMP
      stimulation was observed with dopamine, 5-hydroxytryptamine, 5-methoxytryptamine,
      dimaprit, vasoactive intestinal peptide, SKF-38393, 2-chloroadenosine, CGS-21680,
      prostaglandin D2, secretin and vasopressin. Oxo-M (1 microM) inhibited cAMP
      accumulation by 35% under basal conditions. Oxo-M inhibited specific agonist
      stimulated cAMP levels by 20 to 70%. However, oxo-M caused little or no
      inhibition of specific prostaglandin I2- and cicaprost-stimulated cAMP levels (5
      and 0%, respectively). In general, there was a correlation between the abilities
      of the various agonists to stimulate cAMP accumulation and to cause relaxation of
      the isolated ileum, with an exception being cicaprost. Experiments were carried
      out with isolated ileum to determine whether activation of M2 receptors inhibited
      the relaxant effects of the various agonists. In these experiments, the ileum was
      first treated with N-(2-chloroethyl)-4-piperidinyl diphenylacetate to selectively
      inactivate M3 receptors. After this treatment phase, contractile responses to
      oxotremorine-M were measured in the presence of histamine and a given relaxant
      agent. These measurements were repeated in the presence of the M2-selective
      antagonist AF-DX 116. Analysis of the data showed that part of the contractile
      response to oxotremorine-M could be attributed to an M2-mediated inhibition of
      the relaxation. This M2 component of the contractile response was greatest when
      forskolin or isoproterenol was used as the relaxant agent. In contrast, little or
      no M2 response was measured in the presence of dopamine and cicaprost.

PMID- 8996197
TI  - UDP-glucuronosyltransferase-mediated protection against in vitro DNA oxidation
      and micronucleus formation initiated by phenytoin and its embryotoxic metabolite
      5-(p-hydroxyphenyl)-5-phenylhydantoin.
AB  - UDP-Glucuronosyltransferases (UGTs) are important in the elimination of most
      xenobiotics, including 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), the major,
      reputedly nontoxic, metabolite of the anticonvulsant drug phenytoin. However,
      HPPH alternatively may be bioactivated by peroxidases, such as prostaglandin H
      synthase, to a reactive intermediate that initiates DNA oxidation (reflected by 8
      hydroxy-2'-deoxyguanosine), genotoxicity (reflected by micronuclei) and
      embryopathy. This hypothesis was evaluated in skin fibroblasts cultured from
      heterozygous (+/j) and homozygous (j/j) UGT-deficient Gunn rats and in mouse
      embryo culture, with confirmation of direct NG-glucuronidation of phenytoin in
      Gunn rats in vivo. HPPH (80 microM) increased micronuclei by 2.0-, 4.8- and 4.6
      fold in +/+ UGT-normal cells (P = .03) and +/j and j/j UGT-deficient cells (P =
      .0001), respectively. HPPH-initiated micronucleus formation was increased 3.0-
      and 3.4-fold in +/j (P = .02) and j/j (P = .04) UGT-deficient cells,
      respectively, vs. +/+ UGT-normal cells. Micronuclei were not initiated by 10
      microM HPPH in +/+ UGT-normal cells but were increased by 4- and 3.8-fold in +/j
      and j/j UGT-deficient cells (P = .0001), respectively, and were increased 2.7-
      and 3.0-fold in +/j (P = .007) and j/j (P = .0002) UGT-deficient cells,
      respectively, vs. +/+ UGT-normal cells. 8-Hydroxy-2'-deoxyguanosine was increased
      in j/j UGT-deficient but not +/+ UGT-normal cells treated with 80 microM HPPH (P
      < .05). The embryopathic potency of 80 microM HPPH in embryo culture, reflected
      by decreases in anterior neuropore closure, turning, yolk sac diameter and crown
      rump length (P < .05), was equivalent to that reported for phenytoin. Phenytoin
      (80 microM) enhanced micronucleus formation 1.7-, 4.4- and 3.8-fold in +/+ cells
      (P = .03) and +/j and j/j UGT-deficient cells (P = .0001), respectively.
      Phenytoin-initiated micronucleus formation was increased about 4-fold in both +/j
      (P = .006) and j/j (P = .009) UGT-deficient cells vs. +/+ UGT-normal cells,
      providing the first evidence that the bioactivation and oxidative toxicity of
      phenytoin itself may be avoided by direct N-glucuronidation, which was confirmed
      by tandem mass spectrometry. These results further indicate that, with UGT
      deficiencies, HPPH potentially is a potent mediator of phenytoin-initiated
      genotoxicity and embryopathy, which may be relevant to teratogenesis and other
      adverse effects of phenytoin.

PMID- 8996198
TI  - The influence of endogenous catecholamines on the inhibitory effects of rolipram
      against early- and late-phase response to antigen in the guinea pig.
AB  - Selective inhibitors of the low-Km cAMP-specific phosphodiesterase (PDE4) inhibit
      inflammatory cell function and relax airway smooth muscle. Thus PDE4 inhibitors
      may be useful in the therapy of asthma. The present study was conducted to
      determine whether the in vivo activity of rolipram, a prototypical PDE4
      inhibitor, is due to its ability to potentiate the anti-inflammatory effects of
      prostaglandins or catecholamines, endogenous activators of adenylyl cyclase, in
      models of the early- and late-phase response to antigen. Rolipram, administered
      i.v. to anesthetized, paralyzed and ventilated ovalbumin-sensitized guinea pigs,
      inhibited i.v. antigen-induced bronchoconstriction with an ID50 value of 0.2
      mg/kg. Pretreatment with either of the beta adrenoceptor antagonists propranolol
      and nadolol (0.5 mg/kg i.v.), enhanced the bronchial reactivity to antigen and
      abolished the inhibitory activity of rolipram (0.1-10 mg/kg i.v.). In addition,
      the inhibitory activity of three structurally dissimilar PDE4 inhibitors was
      nearly abolished by propranolol. Cyclooxygenase inhibition by indomethacin
      slightly enhanced the reactivity to antigen but did not affect the inhibitory
      activity of rolipram. Plasma catecholamine concentrations were not altered by
      rolipram (0.3 or 1 mg/kg i.v.), which indicates that there was no stimulation of
      catecholamine release. Bilateral adrenalectomy reduced plasma epinephrine
      concentrations (from 1700 pg/ml to 400 pg/ml), significantly enhanced airway
      reactivity to antigen and substantially reduced the inhibitory activity of
      rolipram (3 mg/kg i.v.). Pretreatment of conscious guinea pigs with the beta
      adrenoceptor antagonist nadolol, 2 mg/kg p.o., enhanced aerosol antigen-induced
      bronchoconstriction and pulmonary eosinophil influx measured by bronchoalveolar
      lavage. Nadolol reduced the inhibitory effect of rolipram against antigen-induced
      bronchoconstriction but not eosinophil influx. The inhibitory effect of rolipram
      was unaffected by indomethacin. The present data suggest that circulating
      catecholamines play an important protective role against antigen-induced broncho
      constriction in the guinea pig. Moreover, the inhibitory activity of PDE4
      inhibitors against antigen-induced bronchoconstriction, but not eosinophil
      influx, is reduced by beta adrenergic blockade or adrenalectomy. Thus the
      inhibitory activity of PDE4 inhibitors against antigen-induced
      bronchoconstriction may be related to their synergism with endogenous
      catecholamines to suppress mast cell degranulation.

PMID- 8996199
TI  - Reabsorption of the nephrotoxin ochratoxin A along the rat nephron in vivo.
AB  - Ochratoxin A (OTA) is a widespread nephrotoxin excreted to a substantial degree
      via the kidney. We investigated whether [3H]OTA is reabsorbed from the tubular
      lumen along the nephron and thus recycles within the kidney. Superficial early
      proximal and early distal tubules of male Wistar rats were micropunctured in
      situ. Microinfusion of OTA into superficial nephrons showed that it was
      reabsorbed in proximal as well as distal parts of the nephron. Reabsorption
      during early distal microinfusion was not saturable in the range of 0 to 5.10(-4)
      mol/liter and accounted for 20% of OTA infused. Reabsorption during early
      proximal microinfusion was partially saturable and reached values up to 70% of
      OTA infused. The apparent K(m) for OTA reabsorption was 236.10(-5) mol/liter and
      maximum transport rate 970 fmol/min/nephron. OTA reabsorption was pH dependent
      and decreased from 70 to 40% during proximal infusion and from 20 to 10% during
      distal infusion when pH increased from 6.0 to 7.4. The dipeptides carnosine and
      glyclysarcosine reduced OTA reabsorption significantly. L-Phenylalanine showed no
      significant inhibitory action. From our results we conclude: 1) there is
      substantial reabsorption of OTA along the nephron; 2) one-third of reabsorption
      takes place in the distal tubule and/or the collecting duct, two-thirds in the
      proximal tubule; 3) "distal" reabsorption can be explained at least in part by
      nonionic diffusion, because it was not saturable but pH dependent; 4) "proximal"
      reabsorption was in part mediated by the H(+)-dipeptide cotransporter; 5)
      reabsorption of filtered and secreted OTA delays its excretion and may lead to
      accumulation of the toxin in renal tissue and 6) inhibition of OTA reabsorption
      (e.g., by urine alkalinization) should help to accelerate OTA excretion and thus
      reduce its toxicity.

PMID- 8996200
TI  - Phorbol ester enhancement of IL-3-dependent proliferation of primitive
      hematopoietic progenitors of mice in culture.
AB  - Protein kinase C (PKC) is a Ca++- and phospholipid-dependent protein kinase
      activated by diacylglycerol that is either released from cell membranes in
      response to certain growth factors or mimicked by 12-O-tetradecanoyl phorbol-13
      acetate (TPA). We studied the effects of TPA on interleukin-3 (IL-3)-dependent
      colony formation of mouse bone marrow cells from mice injected with 5
      fluorouracil 2 days before examination in order to clarify the significance of
      PKC in the proliferation of primitive hematopoietic progenitors. Although TPA
      alone did not support colony formation, TPA in combination with IL-3 increased
      colony numbers from 1.5 to 2 times that formed with IL-3 and vehicle. TPA
      increased not only the granulocyte/macrophage colonies, but also the multilineage
      colonies. A sequential colony count showed that TPA, unlike IL-6, did not hasten
      the appearance of colonies. Because TPA enhanced IL-3-dependent colony formation
      derived from lineage-negative marrow cells obtained from mice that received 5-FU
      2 days before, it is possible that it might act directly on primitive
      progenitors. Prolonged pretreatment of marrow cells with TPA prevented TPA
      augmented colony growth. Calphostin C, a specific PKC inhibitor, and certain
      specific tyrosine kinase inhibitors, such as genistein and herbimycin A,
      abrogated the enhancing effects of TPA on IL-3-dependent colony formation. These
      data suggest that TPA had a direct effect on the primitive progenitors and
      enhanced IL-3-dependent colony formation via activation of PKC and certain
      tyrosine kinases.

PMID- 8996201
TI  - Body distribution of free, liposomal and nanoparticle-associated mitoxantrone in
      B16-melanoma-bearing mice.
AB  - B16-melanoma-bearing mice were treated with four different formulations
      containing equivalent doses of the highly effective antineoplastic drug
      mitoxantrone. The formulations were: A mitoxantrone solution, a negatively
      charged liposome preparation (small unilamellar vesicles), a 14C-labeled
      polybutylcyanoacrylate- (PBCA) nanoparticle suspension, and a suspension of
      poloxamine 1508-coated 14C-PBCA-nanoparticles. After 1, 4 and 24 hr, three
      animals of each group were killed and the mitoxantrone concentrations in the
      blood, tumor, liver, spleen, heart and bone marrow were determined using an high
      performance liquid chromatography technique. Additionally, the concentrations of
      PBCA particles in the same tissues were measured by scintillation counting to
      compare the mitoxantrone distribution with the corresponding PBCA nanoparticle
      distribution. Each formulation led to a different body distribution profile of
      the drug. Liposomes drastically increased the blood level of mitoxantrone even
      after 24 hr, although free drug was cleared quickly. Liposomes also raised the
      concentration in the liver and spleen, but not the drug level in the tumor. PBCA
      nanoparticles considerably increased the mitoxantrone concentrations in tumor,
      heart and spleen. However, the increase in tumor concentrations was not
      statistically significant due to the high variability. Nevertheless, the tumor
      growth was reduced significantly (P < .05) compared to both, the liposome and the
      solution preparation. The nanoparticle polymer concentrations did not completely
      mirror those of the drug concentrations. Especially in the heart, where no
      nanoparticle polymer radioactivity was found, the particle concentration did not
      completely correspond to the mitoxantrone concentration, revealing that a part of
      the drug was lost from the particles. These pharmacokinetic results correspond to
      parallel therapeutic effects obtained with mitoxantrone-loaded nanoparticles and
      liposomes in the B16 melanoma.

PMID- 8996202
TI  - Effect of tachykinin receptor inhibition in the brain on cardiovascular and
      behavioral responses to stress.
AB  - The neurokinins, substance P (SP) and neurokinin A (NKA) represent natural,
      nonspecific ligands of NK1 and NK2 receptors. In our study in conscious rats, we
      tested the hypothesis that neurokinins, especially SP, are used by neuronal
      circuits to generate cardiovascular and behavioral responses to stress by using
      the selective, high-affinity, nonpeptide antagonists of NK1 and NK2 receptors, CP
      96, 345, RP 67580 and SR 48968, respectively, Formalin injected s.c. through a
      chronically implanted catheter in the region of the lower leg was used as a
      stress stimulus. The antagonists and their inactive enantiomers, RP 68651 and SR
      48965, as a control for nonspecific activity, were injected
      intracerebroventricularly (i.c.v.) 10 min before the s.c. injection of formalin.
      Formalin (2.5%, 50 microliters, s.c.) induced a marked increase in mean arterial
      pressure (MAP) and heart rate (HR) as well as hind limb grooming/biting (HG) as
      the dominant behavioral manifestation. Pretreatment with the NK1 receptor
      antagonist, CP-96,345 (5 nmol, i.c.v.), significantly attenuated only the HR (
      54%; P < .01) but not the MAP response to formalin. The NK1 receptor antagonist,
      RP 67580, injected i.c.v. at doses of 100, 500 and 2500 pmol significantly
      reduced both, the MAP and HR responses to formalin by maximally 63% (P < .01) and
      52% (P < .01), respectively. In a separate set of experiments, we compared the
      effect of the individual and simultaneous blockade of central NK1 and NK2
      receptors on the cardiovascular and behavioral responses to formalin stress.
      Pretreatment with RP 67580 (100 pmol, i.c.v.) attenuated the MAP (-30%; P < .05),
      HR (-40%; P < .01) and HG (P < .05) responses to formalin. The NK2 receptor
      antagonist, SR 48968 (650 pmol, i.c.v.), affected neither the cardiovascular nor
      the behavioral responses. i.c.v. pretreatment with both tachykinin receptor
      antagonists (RP 67580: 100 pmol; SR 48968: 650 pmol) reduced the MAP, HR and HG
      responses to formalin to the same extent as RP 67580 alone. Pretreatment with the
      inactive enantiomers, RP 68651 (100 pmol, i.c.v.) and SR 48965 (650 pmol, i.c.v.)
      did not alter the cardiovascular and behavioral responses to formalin. Our
      results demonstrate that centrally administered NK1 receptor antagonists inhibit
      the cardiovascular and behavioral reactions in response to a noxious stimulus.
      They provide first pharmacological evidence that endogenous SP acts as mediator
      of stress responses in the brain.

PMID- 8996203
TI  - Ca++ sensitizers impair cardiac relaxation in failing human myocardium.
AB  - The present study was aimed at investigating the effect of two Ca++ sensitizers,
      EMD 57033 (without significant phosphodiesterase inhibition) and ORG 30029 (with
      phosphodiesterase inhibition), in myocardium from nonfailing and failing human
      hearts. In nonfailing myocardium both EMD 57033 and ORG 30029 increased force of
      contraction by 280 +/- 27% and 94 +/- 13%, respectively (n = 6); the time to 80%
      relaxation (t80%) by 278 +/- 45% and 155 +/- 21%; and diastolic force by 28 +/-
      8% and 12 +/- 3%, respectively. In trabeculae from failing myocardium, the
      increase in active force was similar to that in nonfailing trabeculae (EMD, 305
      +/- 30%; ORG, 88 +/- 12% (n = 6)). However, the increase in t80% (EMD, 378 +/-
      56%; ORG, 230 +/- 26%) and diastolic force (65 +/- 12%; 24 +/- 5%) was more
      pronounced in failing myocardium. EMD had no effect on the peak of the [Ca++]i
      transient; however, it prolonged the time course of the [Ca++]i transient in both
      nonfailing and failing myocardial fibers. ORG increased the peak of the Ca++
      transient and prolonged the time course in preparations from both nonfailing and
      failing hearts. Both EMD and ORG shifted the [Ca++]-force relationship toward
      lower [Ca++] (EMD > ORG). The Ca++ sensitizers EMD 57033 and ORG 30029 increased
      active force development in nonfailing and failing human myocardium, but both
      impaired relaxation in failing myocardium to a greater extent than in nonfailing
      human myocardium in a concentration-dependent fashion.

PMID- 8996204
TI  - Tissue and species variation in the vascular receptor binding of 3H-P1075, a
      potent KATP opener vasodilator.
AB  - A high-affinity receptor site for 3H-P1075 previously observed in rat aorta has
      been proposed to mediate the vasorelaxation effects of P1075 and other ATP
      sensitive K+ channel (KATP) openers. We tested this hypothesis by correlating the
      receptor binding of 3H-P1075 with its vasorelaxation effects in several isolated
      vascular preparations from three species: rat, rabbit and dog. In rat aorta and
      mesenteric artery, 3H-P1075 (1-5 nM) showed high amounts of specific binding (5
      10 fmol/mg tissue), which was 48 to 79% of total binding. In contrast, little (<
      or = 17%) to no specific binding of 3H-P1075 (1-5 nM) was observed in dog
      coronary artery, dog mesenteric artery or rabbit mesenteric artery. However, all
      vascular preparations studied relaxed with P1075 (1-100 nM), showing maximal
      relaxations at 30 to 100 nM. The P1075 relaxation EC50 values in rat aorta,
      rabbit mesenteric artery and dog coronary artery ranged from 7.5 to 24.1 nM
      depending on the level of contractile activation. Thus, the pharmacological
      effect of P1075 could be correlated with the presence of specific receptor
      binding sites only in rat vascular preparations. These data show that there are
      significant differences in the characteristics of the proposed specific receptor
      site for 3H-P1075 in different vascular preparations from different species, and
      they raise questions regarding the pharmacological significance of this KATP
      opener binding site. Until such questions are resolved, it appears that the study
      of functional significance of this receptor site as well as further biochemical
      characterization of this receptor site may necessitate the use of only the rat
      vascular preparations.

PMID- 8996205
TI  - Neuroleptic-induced mitochondrial enzyme alterations in the rat brain.
AB  - For years, it has been known that neuroleptics have the capacity to interfere
      with the mitochondrial respiratory chain in vitro. We report that haloperidol and
      fluphenazine, classical neuroleptics, cause a generalized reduction in the
      activity of NADH: ubiquinone oxidoreductase (complex I) in the rat brain in vivo,
      an effect that was not observed with the atypical neuroleptic, clozapine. MPTP,
      which bears significant structural similarities with haloperidol, also
      demonstrated a significant reduction in complex I activity after low-dose,
      chronic administration. Interestingly, an increase in the activity of cytochrome
      c oxidase (complex IV), probably reflecting enhanced functional neuronal
      activity, was observed in the frontal cortex of all chronically treated animals,
      an effect that is unlikely to result from compensation for the inhibition of
      complex I. Results suggest that previous findings, in which a reduction in the
      activity of cytochrome-c oxidase was observed in postmortem brain samples from
      schizophrenics, are not dependent on treatment with neuroleptics.

PMID- 8996206
TI  - Persistent spontaneous oral dyskinesias in haloperidol-withdrawn rats neonatally
      lesioned with 6-hydroxydopamine: absence of an association with the Bmax for
      [3H]raclopride binding to neostriatal homogenates.
AB  - To investigate the influence of dopamine (DA) nerves on haloperidol (HAL)-induced
      oral dyskinesias, rats were first injected at 3 days after birth with 6
      hydroxydopamine HBr (200 micrograms i.c.v., salt form; 6-OHDA) or vehicle, after
      desipramine HCl (20 mg/kg i.p., 1 hr) pretreatment. Two months later HAL (1.5
      mg/kg/day, 2 days a week for 4 weeks, then daily for 10 months) was added to the
      drinking water of half the rats. Numbers of vacuous chewing movements, recorded
      in 1-min increments every 10 min for 1 hr, increased from < 5 to about 17 oral
      movements per session in intact rats, 14 weeks after instituting HAL (P < .01 vs.
      intact rats drinking tap water). In HAL-treated 6-OHDA-lesioned rats, oral
      activity increased to > 30 oral movements per session (P < .01 vs. HAL-treated
      intact rats). These levels of oral activity persisted in intact and 6-OHDA
      lesioned rats as long as HAL was administered. After 11 months of HAL treatment,
      but 8 or 9 days after HAL withdrawal, DA was found to be reduced 97%, whereas
      serotonin was increased 29% in the striatum of 6-OHDA-lesioned rats. In HAL
      treated intact and lesioned rats the Bmax for DA D2 binding sites was elevated
      about 70%. With reverse transcription polymerase chain reaction, the mRNA level
      for DA D2L but not D2S receptors was also found to be elevated about 70%. In a
      fraction of 6-OHDA-lesioned rats that were observed for 8 months after HAL
      withdrawal, oral activity persisted without decrement and was not accompanied by
      a change in the Bmax or mRNA level for DA D2 receptors. These findings
      demonstrate that in rats largely DA-denervated as neonates, long-term HAL
      treatment produces an unusually high number of oral movements that persists for 8
      months after HAL withdrawal and is not accompanied by an increase in DA D2
      receptor expression.

PMID- 8996207
TI  - Mechanisms of the contractile effects of levosimendan in the mammalian heart.
AB  - In spontaneously beating guinea pig right atria, levosimendan (LS, or R-[[
      (1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)- phenyl]
      hydrazono]propanedinitrile) exerted a positive chronotropic effect starting at
      0.1 microM. In electrically driven guinea pig left atria, LS (0.1-10 microM)
      increased force of contraction without changing time parameters of contraction.
      In electrically driven right papillary muscles, LS (0.1-10 microM) enhanced force
      of contraction without affecting time parameters of contraction. The maximal
      effect on force of contraction at 10 microM amounted to 130 +/- 8.6% of predrug
      value. The positive inotropic effect of LS in papillary muscles was greatly
      diminished by additionally applied carbachol. In [32P]-labeled guinea pig
      ventricular cardiomyocytes, LS increased the phosphorylation state of
      phospholamban, the inhibitory subunit of troponin and C-protein. The maximal
      effect at 1 microM amounted to 134 +/- 8.6%, 124 +/- 4.2% and 121 +/- 8% of
      control for phospholamben, the inhibitory subunit of troponin and C-protein,
      respectively. LS (1 microM) increased cAMP content from 6.3 +/- 0.3 to 8.1 +/-
      0.3 pmol/mg protein in guinea pig ventricular cardiomyocytes. Furthermore, whole
      cell patch-clamp studies were performed in guinea pig ventricular cardiomyocytes.
      In this setup, 10 microM LS increased the amplitude of L-type Ca++ current to 402
      +/- 86% of predrug value.

PMID- 8996208
TI  - Role of corticosterone in the enhancement of the antibody response after acute
      cocaine administration.
AB  - A model has been developed in which acute cocaine administration results in an
      enhanced T-dependent antibody response to sheep erythrocytes. This enhancement
      occurs when cocaine (30 mg/kg, twice in 1 day) is administered 1 or 2 days before
      sensitization with antigen, in mice older than 16 wk. Acute cocaine has been
      shown to elicit a rise in serum corticosterone, and the administration of
      exogenous corticosterone, under similar conditions as cocaine, also results in a
      similar immunoenhancement. Further evidence in support of a role by
      corticosterone is the lack of an enhancement in adrenalectomized mice and the
      ability of alpha-helical corticotropin releasing factor to block the enhancement
      by cocaine. The role of concomitant epinephrine release from the adrenal was
      addressed by adrenal demedullation. Eliminating epinephrine, but not
      corticosterone release, had no effect on the cocaine-induced immunoenhancement.
      The evidence presented provides support for a major role by corticosterone in
      mediating cocaine's effects on at least one measure of immune function, the T
      dependent antibody response.

PMID- 8996209
TI  - Absorption and excretion of undegradable peptides: role of lipid solubility and
      net charge.
AB  - Absorption and excretion of undegradable peptides were investigated with use of
      octapeptides synthesized from D-amino acids. D-Tyrosine was included in each
      peptide to permit labeling with 125I, D-glutamic acid or D-lysine were included
      to vary net electric charge and D-serine or D-leucine were included to vary lipid
      solubility. Peptides were administered parenterally or orally to normal rats
      drinking 5% glucose or maltose. Forty-five percent of a lipid-insoluble,
      negatively charged octapeptide added to the drinking fluid in milligram
      quantities was absorbed from the intestine and excreted intact in urine; 90% of
      this peptide was recovered in urine after parenteral injection. In contrast,
      lipophilic D-octapeptides were largely excreted in feces, even after subcutaneous
      injection; the amounts excreted in feces were correlated with oil/aqueous
      partition coefficients. Evidence is presented that lipophilic peptides entering
      liver cells combine with bile salts to form hydrophilic complexes that are
      secreted rapidly at high concentration in bile. At physiological concentrations
      of bile salts (5-40 mM) and nanomolar concentrations of peptide the binding is so
      complete that these undegradable peptides are rapidly cleared from liver to
      duodenal fluid in association with the bile salts. After reaching the ileum the
      bile salts are reabsorbed to blood, leaving the original lipophilic peptides to
      be excreted in the feces from which they can be extracted, purified and
      identified by high-pressure liquid chromatography. These mechanisms are discussed
      in relation to a) the paracellular absorption of peptides and other solutes by
      solvent drag and b) the delivery and fate of biologically active peptides.

PMID- 8996210
TI  - Adenosine A2 receptor activation attenuates reperfusion injury by inhibiting
      neutrophil accumulation, superoxide generation and coronary endothelial
      adherence.
AB  - This study tests the hypothesis that adenosine A2 receptor activation reduces
      reperfusion injury by inhibiting neutrophils in a canine model of ischemia and
      reperfusion. In 16 anesthetized, open-chest dogs, the left anterior descending
      coronary artery was ligated for 60 min and reperfused for 3 hr. An intracoronary
      infusion of either the selective adenosine A2 agonist CGS-21680 at 0.2
      microgram/kg/min (n = 8) or vehicle (n = 8) was started 5 min before reperfusion
      and discontinued after 60 min. The area at risk was comparable between vehicle
      treated and CGS-21680-treated groups (39.6 +/- 4.1 vs. 37.1 +/- 2.5% of left
      ventricle). Infarction size, determined with triphenyltetrazolium chloride, was
      smaller in the CGS-21680-treated group than in the vehicle-treated group (15.4 +/
      2.9 vs. 29.8 +/- 2.3% of area at risk, P < .05 vs. vehicle-treated group). CGS
      21680 significantly reduced neutrophil accumulation (myeloperoxidase activity) in
      the nonnecrotic area at risk tissue, compared with the vehicle-treated group
      (2.12 +/- 0.5 vs. 6.47 +/- 0.6 U/g of tissue, P < .05 vs. vehicle-treated group).
      In in vitro studies, CGS-21680 reduced platelet-activating factor (PAF)-activated
      canine neutrophil adherence to the endothelial surface of normal homologous
      coronary artery segments. Compared with PAF-stimulated neutrophils (188.4 +/- 9.4
      adhered neutrophils/mm2), CGS-21680 reduced adherence close to base-line levels
      (46.6 +/- 5.8 adhered neutrophils/mm2) at concentrations of 10 microM (65.6 +/-
      8.2 adhered neutrophils/mm2, P < .05 vs. PAF-stimulated group) and 50 microM
      (56.6 +/- 4.6 adhered neutrophils/mm2, P < .05 vs. PAF-stimulated group).
      Superoxide anion production (cytochrome c reduction) by activated neutrophils was
      reduced by CGS-21680 from 33.8 +/- 5.0 to 8.9 +/- 3.6 nmol/5 min/5 x 10(5) cells
      (P < .05 vs. PAF-stimulated group). We conclude that specific A2 receptor
      stimulation with CGS-21680 at reflow reduces reperfusion injury by inhibiting
      neutrophil-related processes.

PMID- 8996211
TI  - Correlation between in vitro and in vivo activity of amoxicillin against
      Streptococcus pneumoniae in a murine pneumonia model.
AB  - We studied the relationship between in vitro bacteriological parameters [minimal
      inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and
      killing rate, defined as the reduction in the inoculum within 1, 3 or 6 hr] and
      in vivo activity of amoxicillin against 12 strains of Streptococcus pneumoniae,
      with penicillin MICs of < 0.01 to 16 micrograms/ml, in a cyclophosphamide-induced
      neutropenic murine pneumonia model. Dose-response curves were determined for
      amoxicillin against each strain, and three quantitative parameters of in vivo
      amoxicillin activity were defined, i.e., maximal attainable antimicrobial effect
      attributable to the drug [i.e., reduction in log colony-forming units (CFU) per
      lung, compared with untreated controls], dose required to reach 50% of maximal
      effect and dose required to achieve a reduction of 1 log CFU/lung. We
      demonstrated a highly significant correlation between the dose required to reach
      50% of maximal effect and MIC (Spearman r = 0.98, P < .0001) or MBC (Spearman r =
      0.95, P < .0001) for amoxicillin against strains of S. pneumoniae with a wide
      range of amoxicillin MICs (0.01-8 micrograms/ml). Significant correlations
      between the dose required to achieve a reduction of 1 log CFU/lung and MIC
      (Spearman r = 0.98, P < .0001) or MBC (Spearman r = 0.95, P < .0001) were also
      observed. In contrast, there were no significant correlations between the maximal
      attainable antimicrobial effect attributable to the drug and MIC, MBC or killing
      rate or between killing rate and the dose required to reach 50% of maximal effect
      or the dose required to achieve a reduction of 1 log CFU/lung. We conclude that
      in vitro susceptibility test results (MICs and MBCs) correlated well with in vivo
      amoxicillin activity against pneumococcal strains, including highly penicillin
      resistant strains, in this animal model. Furthermore, these data suggest that the
      estimated MIC breakpoints for amoxicillin against S. pneumoniae would be 2
      micrograms/ml for intermediate-resistant and 4 micrograms/ml for resistant,
      although this remains to be confirmed in clinical studies.

PMID- 8996212
TI  - Effects of negative allosteric modulators of gamma-aminobutyric acidA receptors
      on complex behavioral processes in monkeys.
AB  - A multiple schedule of repeated acquisition and performance of conditional
      discriminations was used to characterize the effects of two negative allosteric
      modulators of the gamma-aminobutyric acid (GABAA) receptor (ethyl beta-carboline
      3-carboxylate [beta-CCE] and N-methyl-beta-carboline-3-carboxamide [FG-7142]), a
      hallucinogenic beta-carboline derivative (harmine), a benzodiazepine receptor
      antagonist (flumazenil) and a positive allosteric modulator (alprazolam). In the
      acquisition component, subjects acquired a different discrimination each session.
      Acquisition of a discrimination was defined by a decrease in errors as the
      session progressed. In the performance component, the discrimination was the same
      each session. Responding in both components was maintained by food presentation
      under a variable-ratio schedule. Incorrect responses in both components produced
      a 5-sec timeout. Alprazolam (0.1-18 mg/kg), beta-CCE (0.01-0.32 mg/kg), FG-7142
      (0.1-18 mg/kg) and harmine (0.1-1.8 mg/kg) all dose-dependently decreased
      response rate in both components. However, accuracy of responding-was
      differentially affected by the drugs. Alprazolam selectively and dose-dependently
      increased percent errors in acquisition, whereas beta-CCE increased acquisition
      errors only at the highest doses tested in each subject. In contrast, FG-7142 and
      harmine had no effects on percent errors at doses that virtually eliminated
      responding. In all cases, performance accuracy was generally not affected.
      Flumazenil, at doses that had little or no effect (0.1 and 0.32 mg/kg) or
      occasionally decreased response rates (1 mg/kg) when administered alone, dose
      dependently antagonized the rate-decreasing and error-increasing effects of beta
      CCE, FG-7142 and alprazolam. In contrast, flumazenil failed to antagonize the
      effects of harmine. Thus, the negative allosteric modulators only moderately
      disrupted acquisition in comparison with the positive allosteric modulator, but
      the effects of both types of modulator were antagonized by the benzodiazepine
      antagonist flumazenil.

PMID- 8996213
TI  - Vascular and hemodynamic differences between organic nitrates and nitrites.
AB  - Because nitroglycerin (NTG, an organic nitrate) and isoamyl nitrite have similar
      chemical structures and a common mechanism of vascular relaxation (i.e.,
      conversion to nitric oxide in vascular tissues and activation of guanylyl
      cyclase), it has often been assumed that organic nitrates and nitrites have
      identical pharmacologic actions. Because recent studies have shown that the
      vascular enzymes responsible for nitric oxide generation from organic nitrates
      and nitrites are distinct, we hypothesized that the in vitro vascular actions, in
      vivo hemodynamic effects and tolerance properties (both in vitro and in vivo)
      would be different as well. Isolated blood vessel studies showed that NTG
      provided more stable relaxation effects than ISAN, was more potent and caused
      greater in vitro vascular tolerance. Because the mechanism(s) of vascular
      tolerance in vitro may not be the same as those occurring in vivo, we also
      compared the left ventricular hemodynamic effects and tolerance properties of NTG
      vs. isoamyl nitrite and in congestive heart failure rats. Constant NTG infusion
      (10 micrograms/min) caused initial reductions in left ventricular end-diastolic
      pressure of 45 to 55%, which returned to baseline within 10 hr (tolerance
      development). In contrast, isobutyl nitrite and isoamyl nitrite (45
      micrograms/min) caused initial reductions in left ventricular end-diastolic
      pressure similar to NTG (42-58%), but these hemodynamic effects of organic
      nitrites were maintained even when infusions were carried out to 22 hr. These
      results show that organic nitrites and organic nitrates are not pharmacologically
      identical (in vitro or in vivo), and may suggest a therapeutic advantage for
      organic nitrites in the treatment of some cardiovascular diseases.

PMID- 8996214
TI  - Kinetic studies of desensitization and resensitization of the relaxation response
      to beta-2 adrenoceptor agonists in isolated guinea pig trachea.
AB  - Activation of beta-2 adrenoceptors (BAR) in smooth muscle preparations is
      associated with a rapid, reversible and incomplete receptor desensitization,
      resulting in a steady-state relaxation response to BAR agonists. Based on results
      from cell culture studies, we hypothesize that, in the isolated guinea pig
      trachea, this steady state is a result of a concurrent resensitization of
      desensitizing BAR. In tracheal segments maintained at mechanical tone (4-6 g),
      isoproterenol (ISO) and the partial BAR agonist salbutamol (SALB) elicited a
      monotonic, rapid (1-3 min) and reproducible relaxation response that could be
      maintained for up to 45 min and was completely reversed by propranolol.
      Similarly, tissues preconstricted with 0.1 microM carbachol (CARB) responded with
      a sustained relaxation response to ISO. In contrast, in tissues preconstricted
      with 0.3 to 10 microM CARB or with 75 mM KCl, the relaxation elicited by ISO was
      followed by a slow (20-30 min) and partial restoration of muscle tone ("fade").
      The relaxation and fade were observed when CARB-constricted tissues were relaxed
      with SALB (0.2 or 10 microM) or 10 microM salmeterol. No response to SALB was
      observed when tissues were preconstricted with KCl. The fade met criteria for its
      classification as a homologous desensitization of the relaxation response at the
      BAR level. In desensitized washed tissues, a complete recovery of the original
      relaxation response could be detected within 60 min of drug removal. A
      propranolol- and ICI 118-551-sensitive steady state was achieved 30 to 35 min
      after the addition of BAR agonists to the isolated tissues. A three-compartment
      phenomenological kinetic model accurately described the observed data, defining
      one steady-state and three rate constants, describing relaxation (k1),
      desensitization (k2) and resensitization (k3). The values of k2 and k3 for the
      response to SALB and to salmeterol were significantly larger than those observed
      for ISO. In the presence of KCl, the values of k2 and k3 for the response to ISO
      were indistinguishable from those measured in the presence of CARB. Given the
      parameters defined by our model, we propose that desensitization and
      resensitization of BAR in the isolated guinea pig trachea are distinct concurrent
      processes whose net result actively maintains a sustained partial relaxation
      response to ISO, SALB or salmeterol. The component of resensitization in the
      presence of agonist may account for the clinical efficacy of inhaled BAR
      agonists.

PMID- 8996215
TI  - Pharmacological characterization of recombinant human neuronal nicotinic
      acetylcholine receptors h alpha 2 beta 2, h alpha 2 beta 4, h alpha 3 beta 2, h
      alpha 3 beta 4, h alpha 4 beta 2, h alpha 4 beta 4 and h alpha 7 expressed in
      Xenopus oocytes.
AB  - Human neuronal nicotinic acetylcholine receptors (nAChRs) h alpha 2 beta 2, h
      alpha 2 beta 4, h alpha 3 beta 2, h alpha 3 beta 4, h alpha 4 beta 2, h alpha 4
      beta 4 and h alpha 7 were expressed in Xenopus oocytes and tested for their
      sensitivities to the nicotinic agonists acetylcholine (ACh), nicotine, cytisine
      (CYT) and 1,1-dimethyl-4-phenylpiperazinium (DMPP) and the nAChR. antagonists
      mecamylamine (MEC), d-tubocurarine and dihydro-beta-erythroidine. CYT was the
      least efficacious agonist at hnAChRs containing beta 2 subunits, but it displayed
      significant activity at h alpha 2 beta 4, h alpha 3 beta 4, h alpha 4 beta 4 and
      h alpha 7 nAChRs. ACh was one of the most efficacious agonists at all hnAChRs,
      except at h alpha 3 beta 2, where DMPP was markedly more efficacious than ACh.
      ACh was among the least potent agonists at all hnAChRs. The rank order of potency
      displayed by h alpha 3 beta 2 and h alpha 3 beta 4 nAChRs (DMPP approximately CYT
      approximately nicotine > ACh and DMPP > CYT approximately nicotine > ACh,
      respectively), differs from that reported for their rat homologs (Luetje and
      Patrick, 1991; Covernton et al., 1994). The agonist profile observed in h alpha 7
      also differs from that reported for its rat homolog (Seguela et al., 1993). Human
      alpha 4 beta 2 and h alpha 4 beta 4 nAChRs were more sensitive to dihydro-beta
      erythroidine than d-tubocurarine, whereas h alpha 7 and h alpha 3 beta 4 were
      more sensitive to d-tubocurarine than dihydro-beta-erythroidine. These
      antagonists were equipotent at h alpha 2 beta 2, h alpha 3 beta 2 and h alpha 2
      beta 4 nAChRs. MEC (3 microM) inhibited h alpha 2 beta 4 and h alpha 4 beta 4
      nAChRs by > 80%, whereas h alpha 2 beta 2, h alpha 4 beta 2 and h alpha 7 nAChRs
      were inhibited by approximately 50%. Taken together, the differential
      sensitivities observed at various recombinant hnAChR subtypes indicate that both
      alpha and beta subunits contribute to the pharmacology of these ligand-gated
      channels. The unique selectivity profiles displayed by human nAChRs constitute a
      valuable tool for the development of selective nicotinic analogs as potential
      therapeutic drugs.

PMID- 8996216
TI  - N-methyl-D-aspartate antagonist activity of alpha- and beta-sulfallorphans.
AB  - Resolved equatorial (alpha) and axial (beta) forms of S-allylmorphinans, alpha
      sulfallorphan and beta-sulfallorphan, were tested for their ability to compete
      with the binding of phencyclidine and sigma receptor ligands to mouse brain
      membranes and to antagonize N-methyl-D-aspartate (NMDA)-induced convulsions in
      mice. alpha- and beta-sulfallorphans displayed distinct binding affinities for
      phencyclidine and sigma sites, inhibiting the binding of [3H]-(5R,10S)-(+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten++ +-5, 10-imine ([3H]MK-801) with
      Ki values of 2.32 and 0.13 microM and that of [3H](+)-pentazocine with Ki values
      of 1.97 and 1.61 microM, respectively. Intracerebroventricular administration of
      these compounds in mice caused dose-dependent inhibitions of NMDA-induced
      convulsions, but did not affect convulsions induced by (R,S)-alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainic acid and bicuculline.
      alpha- and beta-sulfallorphans blocked the convulsive activity of NMDA (1
      nmol/mouse; intracerebroventricular) with ED50 values of 0.48 and 0.015
      nmol/mouse, as compared with 0.55, 0.039 and 0.013 nmol/mouse for dextrorphan, MK
      801 and (+/-)3-(2-carboxypiperazine-4yl)propyl-1-proprionic acid, respectively.
      The structurally related compound, dextrallorphan, significantly but less
      potently blocked NMDA-induced convulsions (ED60, 2.68 nmol/mouse). At the
      protective doses, alpha- and beta-sulfallorphans markedly reduced NMDA- and AMPA
      induced mortality without inducing locomotion and falling behavior. These results
      indicate that alpha- and beta-sulfallorphans are potent and selective NMDA
      antagonists devoid of motor side effects at protective doses.

PMID- 8996217
TI  - Inhibition of DNA synthesis by aspirin in Swiss 3T3 fibroblasts.
AB  - In Swiss 3T3 fibroblasts, aspirin inhibited proliferation induced by the complete
      mitogenic factors platelet-derived growth factor (PDGF) and bombesin. Aspirin
      decreased the maximum mitogenic effect of bombesin without modifying the
      concentration necessary to obtain half maximal DNA synthesis stimulation. In
      contrast, aspirin only decreased mitogenesis at subsaturating PDGF
      concentrations. The effect of aspirin was found to be concentration dependent.
      The half-maximal effect occurred at approximately 150 microM. The maximal
      inhibition was obtained when aspirin was added during the first hour after growth
      factor addition. At this time, both PDGF and bombesin induced prostaglandin E2
      synthesis. PDGF induced much higher levels of prostaglandin E2 than bombesin. The
      inhibitory effects of aspirin on PDGF or bombesin-stimulated DNA synthesis were
      counteracted by 280 nM prostaglandin E2. Aspirin effects were overcome by agents
      that increase cellular cyclic adenosine monophosphate levels but not by
      activation of protein kinase C. The significance of the antiproliferative action
      of aspirin might be associated with epidemiological data that show a reduced
      incidence of colorectal and other cancers after aspirin treatment.

PMID- 8996218
TI  - Pharmacological characterization of SIB-1765F: a novel cholinergic ion channel
      agonist.
AB  - Nicotine, the prototypical agonist for neuronal nicotinic acetylcholine receptors
      (NAChR), nonselectively activates NAChR limiting its use in elucidating the
      function of NAChR subtypes. SIB-1765F is a subtype selective NAChR agonist that
      displaces [3H]-nicotine binding with an IC50 of 4.6 nM and [3H]-cytisine binding
      with an IC50 of 12.2 nM which is 2000- to 6000-fold lower than its displacement
      of [3H]-QNB or [125I]-alpha-bungarotoxin. SIB-1765F did not inhibit human or rat
      cholinesterases or the uptake of [3H]-DA in synaptosomal preparations. SIB-1765F
      mimicked (-)-nicotine in stimulating [3H]-DA release from rat striatal and
      olfactory tubercle slices, with EC50 values of 99.6 and 39.6 microM,
      respectively. Such stimulation was sensitive to mecamylamine and DH beta E. SIB
      1765F also released endogenous DA in the striatum and the nucleus accumbens as
      measured by in vivo microdialysis. SIB-1765F was less efficacious than (-)
      nicotine at stimulating [3H]-NE release from rat hippocampal slices; in contrast,
      SIB-1765F increased [3H]-NE release from rat thalamic and cortical slices with
      efficacies approaching those of (-)-nicotine. Similar to (-)-nicotine and (+/-)
      epibatidine, subcutaneous administration of SIB-1765F increased the turnover rate
      of dopamine ex vivo both in the striatum and olfactory tubercles in a
      mecamylamine-sensitive manner. Because the release of striatal DA and hippocampal
      NE appears to be regulated by distinct NAChR, differential effects of SIB-1765F
      on striatal DA and hippocampal NE release supports the NAChR subtype selectivity
      of SIB-1765F compared to (-)-nicotine. This is further demonstrated by
      observations showing that SIB-1765F has a higher affinity for h alpha 4 beta 2
      NAChR relative to h alpha 4 beta 4 NAChRs in displacing [3H]-epibatidine binding
      and increasing cytosolic CA+2 concentration in cell lines stably expressing h
      alpha 4 beta 2 or h alpha 4 beta 4.

PMID- 8996219
TI  - Effects of a novel cholinergic ion channel agonist SIB-1765F on locomotor
      activity in rats.
AB  - SIB-1765F ([+/-]-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine fumarate) is a
      novel nicotinic acetylcholine receptor (NAChR) agonist displaying a different in
      vitro pharmacological profile than nicotine and epibatidine, suggestive of NAChR
      subtype selectivity. Our study describes the effects of SIB-1765F on locomotor
      activity in rats, which were compared to those observed for nicotine and
      epibatidine. The three NAChR agonists decreased or increased locomotor activity
      in rats naive or habituated to the test apparatus, respectively. The transient
      reduction in locomotor activity induced by SIB-1765F was quantitatively similar
      to those induced by nicotine and epibatidine but, unlike the effects of nicotine
      and epibatidine, was not blocked by the NAChR antagonists mecamylamine and
      dihydro-beta-erythroidine, suggesting different mechanisms of action.
      Furthermore, SIB-1765F produced a larger and longer-lasting increase in locomotor
      activity when administered to rats familiar with the test apparatus. Mecamylamine
      and dihydro-beta-erythroidine but not hexamethonium blocked the increase in
      locomotor activity induced by SIB-1765F, suggesting that SIB-1765F elicits this
      effect predominantly through the activation of central NAChR. The SIB-1765F
      induced increase in locomotor activity was also attenuated by selective D1 and D2
      dopamine receptor antagonists, implying that this increase in locomotor activity
      is mediated through the activation of dopamine receptors subsequent to the
      release of dopamine. Based on these results, SIB-1765F appears to have a
      different locomotor activity profile than nicotine and epibatidine.

PMID- 8996220
TI  - Interactions between a novel cholinergic ion channel agonist, SIB-1765F and L
      DOPA in the reserpine model of Parkinson's disease in rats.
AB  - SIB-1765F, a novel nicotinic acetylcholine receptor agonist, was tested for its
      efficacy in attenuating reserpine-induced hypolocomotion in rats. SIB-1765F was
      administered alone or in combination with L-DOPA and its effects were compared to
      those of nicotine, d-amphetamine and amantadine in the same conditions.
      Consistent with previous reports, reserpine-induced hypolocomotion was reversed
      by L-DOPA (plus benserazide), d-amphetamine and amantadine in a dose-dependent
      manner and the effect of L-DOPA in reserpine-treated rats was potentiated by
      amantadine. SIB-1765F also increased the locomotor activity of reserpine-treated
      rats and potentiated the effect of L-DOPA on reserpine-induced hypolocomotion.
      The onset of potentiation of L-DOPA by SIB-1765F was rapid (< 5 min) compared to
      the onset of potentiation by amantadine (> 105 min). Interestingly, nicotine did
      not attenuate reserpine-induced hypolocomotion nor did it affect the action of L
      DOPA on reserpine-treated rats. Biochemical analysis of levels of dopamine and
      its metabolites, dihydroxyphenylacetic and homovanillic acid, indicated that, in
      contrast to amphetamine, SIB-1765F did not inhibit dopamine reuptake. The effect
      of SIB-1765F in reserpine-treated rats was attenuated by alpha-methyl-p-tyrosine,
      implying that SIB-1765F acts by releasing dopamine from both reserpine
      insensitive and reserpine-sensitive pools. Our findings demonstrate that
      nicotinic acetylcholine receptor agonists may offer a new therapeutic approach to
      the symptomatic treatment of the motor deficits in patients with Parkinson's
      disease.

PMID- 8996222
TI  - Structure-internalization relationship for adsorptive-mediated endocytosis of
      basic peptides at the blood-brain barrier.
AB  - For the purpose of the brain delivery of peptides, the structural specificity of
      adsorptive-mediated endocytosis at the blood-brain barrier was studied by
      measuring transport of a newly synthesized basic peptide 001-C8, H-MeTyr-Arg
      MeArg-D-Leu-NH(CH2)aNH2, using primary cultured bovine brain capillary
      endothelial cells. The apparent uptake of [125I]001-C8 increased time-dependently
      and reached a steady-state at 60 min. The steady-state uptake of [125I]001-C8 was
      temperature and concentration dependent and was significantly decreased in the
      presence of dansylcadaverine, protamine or poly-L-lysine. Uptakes of peptides
      modified by 1,8-octanediamine, 1,5-pentanediamine, 1,2-ethanediamine or
      ethylamide and peptides with a free carboxyl terminal were significantly higher
      than, and similar to, that of [3H]PEG900, respectively. The half-saturation
      constants and the maximal uptake capacities of these peptides were in the ranges
      of 0.2 to 134 microM and 1.1 to 408 pmol/mg protein, respectively. These values
      were correlated with the basicity of the molecules. In conclusion, not the number
      of constituent amino acids of peptides, but rather the C-terminal structure and
      the basicity of the molecules are the most important determinants for the uptake
      by the adsorptive-mediated endocytosis system at the blood brain barrier.

PMID- 8996221
TI  - Blood-brain barrier permeability and bioavailability of a highly potent and mu
      selective opioid receptor antagonist, CTAP: comparison with morphine.
AB  - D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) is a cyclic, penicillamine
      containing octapeptide that is structurally similar to somatostatin and displays
      greater antagonist potency and selectivity for mu-opioid receptors, compared with
      the classical mu-selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2.
      The aim of this study was to determine whether CTAP can enter the central nervous
      system (CNS) by crossing either the blood-brain barrier or the blood
      cerebrospinal fluid barrier (CSF) and to characterize the mechanism of CNS entry.
      CNS entry of [3H]CTAP was compared with that of the vascular space marker
      [14C]inulin and the mu-agonist [3H]morphine. By using an in situ brain perfusion
      technique coupled to high-performance liquid chromatographic analysis, greater
      amounts of radioactivity were detected in the brain or CSF at most time points
      for [3H]CTAP, compared with [14C]inulin. [3H]CTAP was found to remain
      predominantly intact in the brain after a 20-min rat brain perfusion (62.8%).
      CTAP was also stable in the blood and serum of rats (T1/2 > 500 min), showing
      that the structure of this peptide offers enzymatic resistance. Additionally,
      [3H]CTAP was found to be extensively protein-bound to albumin in the perfusion
      medium (68.2%) and to proteins in rat serum (84.2%). Entry into the brain and CSF
      was not inhibited by the addition of unlabeled CTAP to the perfusion medium,
      suggesting that passage into the CNS is most likely through diffusion across the
      membranes that comprise the blood-brain barrier, rather than by saturable
      transport. Also, greater amounts of [3H]morphine entered both the brain and CSF
      after a 20-min brain perfusion, compared with [3H]CTAP. The increased CNS
      penetration observed for [3H]morphine, compared with [3H]CTAP, is likely due to
      the increased lipophilicity of morphine, as shown by its higher octanol/saline
      partition coefficient. Based on the pharmacokinetic profile, CTAP may be a
      promising mu-selective antagonist that can be used as a treatment for opiate
      overdose or addiction and also as a pharmacological tool to further understand
      opioid neurobiology.

PMID- 8996224
TI  - (2S,4R)-4-methylglutamic acid (SYM 2081): a selective, high-affinity ligand for
      kainate receptors.
AB  - Glutamic acid activates ionotropic glutamate receptors that mediate excitatory
      transmission in the central nervous system. The introduction of a methyl group at
      position 4 of glutamic acid imparts selectivity for kainate receptors, relative
      to other (N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid) ionotropic glutamate receptors. Among the stereoisomers
      of 4-methylglutamic acid, the potency of the (2S,4R)-isomer (SYM 2081) to inhibit
      [3H]kainic acid binding to both wild-type (rat forebrain) and recombinant (GluR6)
      kainate receptors (IC50 values of approximately 32 and 19 nM, respectively) was
      comparable to that of kainic acid (IC50 values of approximately 13 and 28 nM,
      respectively). SYM 2081 was approximately 800- and 200-fold less potent as an
      inhibitor of radioligand binding to wild-type (rat forebrain) alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptors,
      respectively. Preexposure of human embryonic kidney 293 cells stably expressing
      GluR6 receptors to low concentrations of SYM 2081 (30-300 nM) resulted in a
      reversible blockade of the rapidly desensitizing currents produced by kainate
      application. At higher concentrations, SYM 2081 (EC50 of approximately 1 microM)
      elicited kainate-like, rapidly desensitizing, inward currents. Pretreatment of
      recombinant GluR6 receptors with concanavalin A both abolished the effect of SYM
      2081 to block kainate-induced currents and revealed nondesensitizing currents
      induced by SYM 2081 alone. The latter observations provide strong support for the
      hypothesis that SYM 2081 blocks kainate-induced currents through a process of
      agonist-induced desensitization. SYM 2081 also activated alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid receptor currents in primary cultures of
      cerebral cortex and, consistent with data obtained by radioligand binding, was
      approximately 5-fold less potent than kainate (EC50 values of 325 and 70 microM,
      respectively) in this measure. SYM 2081 is a high-affinity, selective, kainate
      agonist that may prove useful both as a probe to examine the physiological
      functions of kainate receptors and as the prototype of a novel class of
      therapeutic agents.

PMID- 8996223
TI  - Dynorphin A1-13 stimulates ovine fetal pituitary-adrenal function through a novel
      nonopioid mechanism.
AB  - We previously reported that U50488H, a kappa-selective opioid agonist, stimulates
      the release of adrenocorticotropin (ACTH) in the ovine fetus via the release of
      hypothalamic arginine vasopressin and corticotropin releasing factor. In this
      study we examined the effects of the endogenous kappa-preferring opioid peptide,
      dynorphin A1-13, on fetal ACTH release using the unanesthetized, chronically
      catheterized fetal lamb model. Fetal plasma samples were collected at timed
      intervals after fetal administration of dynorphin A1-13 (0.5 mg/kg, i.v.) and
      subsequently analyzed by radioimmunoassay for immunoreactive-ACTH and
      immunoreactive-cortisol. Dynorphin A1-13 produced a highly significant and rapid
      increase in immunoreactive-ACTH (P = .002) and immunoreactive-cortisol (P = .002)
      with peak levels of 383.3 +/- 43.8 pg/ml and 32.8 +/- 9.0 ng/ml, respectively, at
      15 min after administration. A similar increase in plasma immunoreactive-ACTH was
      seen after the same dose of dynorphin A1-17 (P = .02) but not dynorphin A2-17.
      This ACTH response to dynorphin A1-13 was shown to be insensitive to the opioid
      antagonist, naloxone (12 mg/hr), as well as antagonists of corticotropin
      releasing factor and arginine vasopressin. These data suggest that dynorphin A1
      13 in the ovine fetus may be acting through a mechanism distinct from the kappa
      opioid system and that the dynorphins may serve as secretagogues of ACTH directly
      at the anterior pituitary through nonopioid receptors.

PMID- 8996225
TI  - Activation of the recombinant human alpha 7 nicotinic acetylcholine receptor
      significantly raises intracellular free calcium.
AB  - The alpha 7 nicotinic acetylcholine receptor (nAChR) subtype, unlike other
      neuronal nicotinic receptors, exhibits a relatively high permeability to Ca++
      ions. Although Ca++ entry through this receptor subtype has been implicated in
      various Ca(++)-dependent processes in the central nervous system, little is known
      about how this receptor modulates mammalian intracellular Ca++ dynamics.
      Intracellular Ca++ responses evoked by activation of the human alpha 7 nAChRs
      stably expressed in HEK-293 (human embryonic kidney) cells were studied. Inward
      current and intracellular Ca++ transients were recorded simultaneously in
      response to a fast drug application system. Current recordings under whole-cell
      voltage-clamp and fast ratiometric intracellular Ca++ imaging acquisition were
      synchronized to drug pulses. The mean peak [Ca++]i observed with 100 microM (-)
      nicotine was 356 +/- 48 nM (n = 8). The magnitude of the intracellular Ca++
      elevation corresponds to a 20% fractional current carried by Ca++ ions. The EC50
      of the intracellular Ca++ responses for (-)-nicotine, (+/-)-epibatidine, 1,1
      dimethyl-4-phenyl-piperazinium and acetylcholine were 51, 3.5, 75 and 108 microM,
      respectively. These EC50 values strongly correlate with those recorded for the
      cationic inward current through alpha 7 nAChR. alpha-Bungarotoxin,
      methyllcaconitine or extracellular Ca++ chelation ablated (-)-nicotine-evoked
      increase in intracellular Ca++ concentration. This study provides evidence that
      cation influx through the human alpha 7 nAChR is sufficient to mediate a
      significant, transient, rise in intracellular Ca++ concentration.

PMID- 8996226
TI  - (+)MK-801 does not prevent MPTP-induced loss of nigral neurons in mice.
AB  - The present study was designed to evaluate the effects of 5-methyl-10,11-dihydro
      5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)MK-801] on 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced nigrostriatal damage in the mouse, with the
      goal of clearly defining what protective effects, if any, this noncompetitive N
      methyl-phenyl-1,2,3,6-tetrahydropyridine receptor antagonist may have against
      MPTP neurotoxicity. Animals were treated with MPTP (40 mg/kg s.c.) and/or (+)MK
      801 (3 x 1 mg/kg i.p. at 4-hr intervals starting 30 min before MPTP) and were
      killed at 8 hr and 1, 7 and 21 days after MPTP exposure. Dopamine concentrations
      were measured in the striatum and ventral mesencephalon, and the total number of
      neurons in the substantia nigra was estimated using an unbiased stereological
      technique. Administration of (+)MK-801 before MPTP temporarily prevented MPTP
      induced dopamine depletion. This was observed at 8 hr in the striatum and 1 week
      in the ventral mesencephalon, but not at other time-points studied. In both areas
      of the brain, (+)MK-801 appeared to delay the elimination of the metabolite 1
      methyl-4-phenylpyridinium ion without affecting its formation. A 30% loss of
      nigral neurons with tyrosine hydroxylase immunoreactive and cresyl violet
      staining was seen at 1 and 3 weeks in both groups of MPTP-exposed animals,
      regardless of whether they received (+)MK-801. These data suggest that (+)MK-801
      may affect the acute pharmacological/biochemical events induced by MPTP, but it
      does not have any enduring protective effects on either dopamine concentrations
      and/or the cell loss induced by this neurotoxin in mice.

PMID- 8996227
TI  - HR 720, a novel angiotensin receptor antagonist inhibits the angiotensin II
      induced trophic effects, fibronectin release and fibronectin-EIIIA+ expression in
      rat aortic vascular smooth muscle cells in vitro.
AB  - The aim of this study was to evaluate the direct trophic effects of angiotensin
      II (AII) on rat vascular smooth muscle cells obtained from a single cellular
      isolate. Cell volume, protein synthesis, fibronectin (FN) release and FN-EIIIA+
      mRNA isoform expression were analyzed in parallel. The effects of HR 720, a novel
      AT1 angiotensin receptor antagonist with some AT2 receptor affinity, were
      compared with those of selective AT1 antagonist EXP 3174. Both HR 720 and EXP
      3174 inhibited in a concentration-dependent manner the maximum increase in cell
      volume induced by 10(-9) M Sar1-All (IC50 = 0.49 x 10(-9) M and 0.79 x 10(-9) M,
      respectively). Maximum [3H]leucine incorporation was also achieved at 10(-9) M
      All. HR 720 blocked the increase in protein synthesis with potency similar to EXP
      3174; the respective IC50 values were 1.04 x 10(-9) M and 1.36 x 10(-9) M. All
      dose-dependently increased FN release, which was also equally inhibited by about
      50% with both compounds at 10(-6) M. Furthermore, All enhanced FN-EIIIA+ mRNA in
      rat vascular smooth muscle cells (VSMC), which indicated a modulation of FN
      isoform expression which was inhibited by angiotensin II antagonists. In
      conclusion, All induced parallel and concentration-dependent increases in cell
      volume, protein synthesis, FN release and FN-EIIIA+ mRNA expression in vascular
      smooth muscle cells. These effects appeared to be essentially mediated by AT1
      receptor stimulation as indicated by the equal inhibitory effects of HR 720 and
      EXP 3174.

PMID- 8996228
TI  - Effect of aspirin plus dipyridamole on the retinal vascular pattern in
      experimental diabetes mellitus.
AB  - Platelet hyperactivity has been one of the mechanisms implicated in the
      pathogenesis of diabetic retinopathy. Antiplatelet agents have been shown, in
      experimental models, to prevent the development of retinal vascular abnormalities
      when given from the first day after the onset of diabetes. We assessed the effect
      of aspirin plus dipyridamole (6 + 12 mg/kg daily) on the retinal vascular pattern
      in experimental streptozotocin-induced diabetes in rats, when the treatment was
      given at different intervals after the induction of diabetes, over a 3-month
      study period. Saline-pretreated diabetic rats showed a time-dependent increases
      in the platelet production of thromboxane B2 (r = 0.981, P < .0001) and a
      decrease in the aortic production of 6-keto-PGF1 alpha. The percentage of retinal
      area occupied by horseradish peroxidase-labeled vessels decreased progressively
      in relation to the length of time of the evolution of diabetes (r = 0.983, P <
      .00001) and the thromboxane/prostacyclin ratio. Treatment with aspirin plus
      dipyridamole caused an inhibition of the platelet production of thromboxane B2
      and a decrease in the vascular synthesis of prostacyclin. Treatment with
      antiplatelet agents slowed down the decrease in the percentage of retinal area
      occupied by horseradish peroxidase-labeled vessels. These data provide further
      evidence to support the results of previous clinical trials in which antiplatelet
      agents had a beneficial effect on the evolution of retinal lesions in early
      diabetic retinopathy.

PMID- 8996229
TI  - Mechanisms of the regional hemodynamic effects of a mu-opioid receptor agonist
      microinjected into the hypothalamic paraventricular nuclei of conscious
      unrestrained rats.
AB  - The present study was undertaken to characterize the mechanisms of the
      hemodynamic responses to microinjection of the selective mu-opioid receptor
      agonist [D-Ala2,MePhe4,Gly5-ol]enkephalin (DAMGO) into the paraventricular
      nucleus of the hypothalamus, in conscious rats chronically instrumented with
      pulsed Doppler flow probes. We found that i.v. pretreatment with phentolamine had
      no effect on the tachycardia elicited by DAMGO (1 nmol); however, the pressor
      response was reversed to a state of hypotension, the renal and superior
      mesenteric vasoconstrictions were attenuated and the hindquarter vasodilation was
      potentiated. In the presence of propranolol, the pressor response and renal
      vasoconstriction were unchanged, whereas the superior mesenteric vasoconstriction
      was reduced and the hindquarter vasodilation was abolished. Moreover, in those
      animals we observed bradycardia followed by tachycardia. Combined i.v.
      pretreatment with phentolamine and propranolol abolished the pressor and heart
      rate responses to DAMGO but had no effect on the renal and superior mesenteric
      vasoconstrictions, although the hindquarter vasodilation was reduced. Intravenous
      pretreatment with a vasopressin V1 receptor antagonist or captopril had no effect
      on the cardiovascular responses to DAMGO. Together, these results indicate that
      the hypertension observed after injection of DAMGO into the paraventricular
      nucleus of the hypothalamus was secondary to alpha adrenoceptor-mediated
      vasoconstrictions in renal and superior mesenteric vascular beds and to beta
      adrenoceptor-mediated vasodilation in the hindquarter vascular bed, whereas the
      involvement of circulating vasopressin or angiotensin seems less obvious from the
      present findings. However, we cannot exclude the possibility that nonadrenergic,
      nonvasopressinergic and nonangiotensinergic vasoconstrictor mechanisms were
      acting in the renal and superior mesenteric vascular beds.

PMID- 8996230
TI  - Epileptic activity prevents synapse formation of hippocampal mossy fibers via L
      type calcium channel activation in vitro.
AB  - Hippocampal slice from early postnatal rat was used to elucidate the influence of
      epileptic activity elicited by picrotoxin on synapse formation of mossy fibers.
      Neurite reelongation and synaptogenesis of mossy fibers transected at 8 days in
      vitro were confirmed by staining with Dil, a fluorescent membrane dye used as a
      neuronal tracer, and by recording field excitatory postsynaptic potentials
      (fEPSP) in the CA3 region evoked by stimulation of the dentate gyrus. Picrotoxin
      (50 microM), which evoked spontaneous epileptiform firing in the CA3 region that
      was occluded by tetrodotoxin (1 microM), hindered development of fEPSP amplitude
      after a lesion of mossy fibers. Furthermore, observations using a Timm method, a
      histochemical technique that preferentially labels synaptic terminals of mossy
      fibers, revealed that picrotoxin prevented synaptogenesis in the CA3 region. This
      inhibitory effect of picrotoxin was completely abolished by tetrodotoxin or
      nicardipine (10 microM), a L-type calcium channel blocker, but not by 2-amino-5
      phosphonopentanoic acid (50 microM), a N-methyl-D-aspartate receptor antagonist,
      suggesting that influx of calcium ion via L-type calcium channels during
      epileptic bursts mediated the disturbance of appropriate synapse formation of
      mossy fibers.

PMID- 8996231
TI  - Hydroxyurea induces the gene expression and synthesis of proinflammatory
      cytokines in vivo.
AB  - The anticancer agent hydroxyurea (HU) was previously found to cause dose
      dependent adrenal activation in the rat. The increased secretion of
      corticosterone (CORT) that results appeared to protect animals against HU
      toxicity, which was dramatically enhanced in adrenalectomized (ADX) rats.
      Similarities with the endocrine and toxicological profiles of proinflammatory
      cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF) led us to
      suggest that these effects of HU might be mediated by an increased synthesis of
      these cytokines. The goal of this study was therefore to demonstrate that HU
      induces the gene expression and synthesis of proinflammatory cytokines in vivo.
      Intact and ADX rats were treated with HU, mRNA was extracted from spleen cells 2
      and 24 hr after treatment and message levels for IL-1 alpha, IL-2, IL-4, IL-6,
      TNF alpha and interferon-gamma were evaluated using the reverse transcriptase
      polymerase chain reaction technique. In some experiments, circulating levels of
      CORT and TNF were also measured. We found that transcripts of the proinflammatory
      cytokines, TNF, IL-6 and (though less clearly) IL-1 alpha, were expressed in the
      majority of intact rats treated with HU but were absent or less evident in most
      controls. In contrast, gene expression of IL-2, IL-4 and interferon-gamma was not
      influenced by drug treatment. Adrenalectomy markedly enhanced the effects of HU.
      Twenty-four hours after administration of the drug, the expression of TNF and IL
      6 mRNAs was still higher in ADX rats compared with intact animals. Parallel
      measurements of plasma CORT levels revealed that gene expression of IL-1 alpha
      and, to a lesser extent, TNF was inversely related to levels of circulating CORT.
      Adrenalectomy per se caused a significant increase in plasma TNF levels compared
      with intact controls. Hydroxyurea elicited significant increases in circulating
      TNF in both ADX and intact rats. These findings lend support to our working
      hypothesis and provide an explanation for both the rise in glucocorticoid
      secretion induced by HU in intact rats and the increase in lethality observed in
      animals with disruptions of the hypothalamo-pituitary-adrenal axis.

PMID- 8996232
TI  - Nicorandil activates glibenclamide-sensitive K+ channels in smooth muscle cells
      of pig proximal urethra.
AB  - The effects of nicorandil on ionic currents recorded from single smooth muscle
      cells of pig proximal urethra were investigated using patch-clamp techniques.
      Tension measurement was also performed to study the effects of nicorandil on the
      resting tone of pig urethra. Nicorandil produced a concentration-dependent
      sustained outward current that was suppressed by glibenclamide at -50 mV and was
      carried selectively by K+. In cell-attached configuration, nicorandil activated a
      43-pS K+ channel that was reversibly inhibited by 10 microM glibenclamide. This
      glibenclamide-sensitive 43-pS K+ channel (KGS) "ran down" after excision of the
      membrane patch. In inside-out configuration, the application of either 1 mM Mg
      ATP or 1 mM nucleotide diphosphate reactivated the KGS. In symmetrical 140 mM K+
      conditions, 300 microM nicorandil and 300 microM levcromakalim activated a 2.14
      pA K+ channel that exhibited the same amplitude and similar channel-opening
      kinetics. Methylene blue (10-100 microM), a soluble guanylate cyclase inhibitor,
      did not inhibit the opening of the nicorandil-induced KGS. The KGS was not
      activated by either sodium nitroprusside (10-100 microM) or 8-bromo guanosine
      3':5'-cyclic monophosphate (1 mM). Nicorandil caused a concentration-dependent
      relaxation of the urethral resting tone but was less potent than levcromakalim.
      The relaxation induced by 10 microM nicorandil was partially inhibited by
      glibenclamide (1-10 microM) and also by methylene blue (10-100 microM). These
      results indicate that two independent nicorandil-induced relaxation mechanisms
      may be present in pig urethra.

PMID- 8996233
TI  - Inhibition by hydroxyl radicals of calcitonin gene-related peptide-mediated
      neurogenic vasorelaxation in isolated canine lingual artery.
AB  - Canine lingual arteries are innervated by calcitonin gene-related peptide (CGRP)
      containing vasodilator nerves. Although the vascular system might be considered
      as the first target of oxygen-derived free radicals in some of the
      pathophysiological conditions, the effect of oxygen-derived free radicals on
      neurotransmission in CGRP nerves remains unknown. We, therefore, investigated the
      role of oxygen-derived free radicals generated from Fenton's reagent (3 x 10(-4)
      M H2O2 plus 2 x 10(-4) M FeSO4) on CGRP-mediated neurogenic relaxation of canine
      lingual artery ring preparations. In all experiments, endothelium-denuded
      preparations (which were suspended in the tissue bath for isometric tension
      recordings) were treated with guanethidine (5 x 10(-6) M) to block neurogenic
      constrictor responses. The periarterial nerve stimulation (10 V, 4-16 Hz, for 45
      sec), exogenous CGRP (10(-8) M) or the ATP-sensitive K+ channel opener cromakalim
      (10(-6) M) produced relaxation of the rings at a stable plateau tension by the
      addition of norepinephrine (10(-5) M); the relaxations elicited by CGRP and
      cromakalim were human CGRP-(8-37)- and glibenclamide-abolishable, respectively.
      When the nerve stimulation, CGRP and cromakalim were given after H2O2/FeSO4
      exposure (Fenton's reagent was removed from the tissue bath), the observed
      relaxations were markedly diminished. The effects afforded by the early exposure
      to H2O2/FeSO4 reaction of the preparations were significantly protected by
      catalase (100 U/ml, H2O2 scavenger), dimethylthiourea (1 mM, H2O2 and HO.
      scavenger), dimethyl sulfoxide (100 mM, HO. scavenger), deferoxamine (1 mM, a
      powerful iron chelator) and by a cocktail of catalase-deferoxamine. Generation of
      HO. from H2O2/FeSO4 was studied by electron spin resonance spectroscopy using the
      spintrap 5,5-dimethyl-1-pyrroline-N-oxide. We found that H2O2/ FeSO4 reaction
      formed a 1:2:2:1 quartet, characteristic of the HO-5,5-dimethyl-1-pyrroline-N
      oxide spin adduct. After exposure to capsaicin (10(-5) M) or H2O2/FeSO4 of the
      artery ring preparations, the intensity of CGRP-like immunoreactivity of the
      periarterial nerves was reduced drastically; the relaxation caused by the nerve
      stimulation was nearly fully inhibited by capsaicin and H2O2/FeSO4 reaction. The
      relaxant response, however, to nitroglycerin (10(-5) M) in the presence of
      norepinephrine to induce tone was unaffected by the early H2O2/ FeSO4 exposure.
      The data obtained from the present study indicate that HO., rather than H2O2, is
      the active agent in CGRP-mediated neurogenic relaxation. It is suggested that the
      HO. can deplete endogenous CGRP localized prejunctionally and also damage CGRP
      induced relaxation of canine lingual artery preparations that is caused by
      activation of ATP-sensitive K+ channels at postjunctional sites. It is also
      postulated that the second messenger system of the relaxation mediated, at least,
      by cyclic GMP may be less susceptible to HO..

PMID- 8996234
TI  - Covalent binding of acetaminophen to N-10-formyltetrahydrofolate dehydrogenase in
      mice.
AB  - The analgesic acetaminophen is frequently used as a model chemical to study
      hepatotoxicity; however, the critical mechanisms by which it produces toxicity
      within the cell are unknown. It has been postulated that covalent binding of a
      toxic metabolite to crucial proteins may inhibit vital cellular functions and may
      be responsible for, or contribute to, the hepatotoxicity. To further understand
      the importance of covalent binding in the toxicity, a major cytosolic
      acetaminophen-protein adduct of 100 kDa has been purified by a combination of
      anion exchange chromatography and preparative electrophoresis. N-Terminal and
      internal amino acid sequences of peptides from the purified 100-kDa acetaminophen
      protein adduct were found to be homologous with the deduced amino amino acid
      sequence from the cDNA of N-10-formyltetrahydrofolate dehydrogenase. Antiserum
      specific for N-10-formyltetrahydrofolate dehydrogenase and acetaminophen react in
      a Western blot with the purified 100-kDa acetaminophen-protein adduct.
      Administration of a toxic dose of acetaminophen (400 mg/kg) to mice resulted in a
      25% decrease in cytosolic N-10-formyltetrahydrofolate dehydrogenase activity at 2
      hr. The covalent binding of acetaminophen to proteins such as N-10
      formyltetrahydrofolate dehydrogenase and the subsequent decreases in their enzyme
      activity may play a role in acetaminophen hepatotoxicity.

PMID- 8996235
TI  - Selective centrilobular expression of the aryl hydrocarbon receptor in rat liver.
AB  - The aryl hydrocarbon receptor (AHR) is a transcriptional activator of genes
      encoding a group of drug-metabolizing enzymes, including cytochrome P450 1A1
      (CYP1A1), glutathione S-transferase, tumor-associated aldehyde dehydrogenase and
      quinone reductase. Both the constitutive and inducible expression of these genes
      in the liver is zonated, i.e., dominant in hepatocytes of the centrilobular
      region, a poorly understood position-dependent phenomenon. By comparing cell
      lysates obtained from opposite acinar regions we observed that immunoreactive AHR
      protein was almost exclusively confined to centrilobular cells. The AHR mRNA, as
      analyzed from cell lysates by reverse transcriptase polymerase chain reaction,
      exhibited a similar, although somewhat less pronounced zonation. By contrast,
      only slight zonation of the AHR nuclear translocator mRNA was observed. Treatment
      of rats with omeprazole, an atypical nonligand activator of the AHR, caused a
      zone-specific induction of CYP1A1 in the centrilobular region similar to that
      seen after pretreatment with the AHR ligand 3-methylcholanthrene. Our results
      suggest that the zone-restricted expression of AHR protein will allow the
      constitutive and inducible expression of AHR-regulated genes in the centrilobular
      region, but will limit their expression in the periportal region.

PMID- 8996236
TI  - Chronic morphine treatment increases stimulatory beta-2 adrenoceptor signaling in
      A431 cells stably expressing the mu opioid receptor.
AB  - Chronic opioid regulation of stimulatory beta-2 adrenoceptor (beta-2 AR)
      signaling was investigated in human mammary epidermoid carcinoma A431 cells
      stably expressing the cloned rat mu opioid receptor. In the cell clone used
      (A431/mu 13; Bmax = 302.9 +/- 46 fmol/mg membrane protein), the addition of
      morphine acutely attenuated basal as well as (-)-isoproterenol-stimulated cAMP
      accumulation. Prolonged exposure of the cells to morphine (10 microM; 2 d)
      resulted in homologous desensitization of MOR function as well as heterologous
      sensitization of adenylate cyclase (AC). Up-regulation of AC in A431/mu 13 cells
      is characterized by an increased capacity rather than an increased sensitivity of
      beta-2 AR-stimulated AC. Moreover, opioid withdrawal falls to precipitate a cAMP
      overshoot in this cell system. Sensitization of stimulatory AC signaling by
      chronic morphine develops in a time- and dose-dependent manner and is blocked by
      both naloxone and pertussis toxin. Investigation into the mechanism leading to up
      regulation of AC revealed a 40% increase in the number of beta-2 ARs as assessed
      by [125I]-cyanopindolol binding experiments. No additional quantitative changes
      were found for stimulatory G proteins and the effector enzyme itself.
      Sensitization of AC appears to be mediated solely by the increase in beta-2 AR
      numbers, because (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3- [(1
      methylethyl)amino]-2-butanol hydrochloride, which acts as an "inverse agonist" at
      the beta-2 AR, completely reversed elevated basal AC activities, and because the
      ratio between functional active beta-2 ARs and stimulatory G proteins remained
      unchanged. In conclusion, chronic exposure of clonal A431/ mu13 cells to morphine
      increases the capacity of stimulatory AC signaling by up-regulating beta-2 AR
      number. These results demonstrate participation of stimulatory receptor systems
      in the cellular mechanisms underlying opioid dependence.

PMID- 8996237
TI  - Costimulation of T cell activation by integrin-associated protein (CD47) is an
      adhesion-dependent, CD28-independent signaling pathway.
AB  - The integrin-associated protein (IAP, CD47) is a 50-kD plasma membrane protein
      with a single extracellular immunoglobulin variable (IgV)-like domain, a multiply
      membrane-spanning segment, and alternatively spliced short cytoplasmic tails. On
      neutrophils, IAP has been shown to function in a signaling complex with beta 3
      integrins. However, the function of IAP on T cells, which express little or no
      beta 3 integrin, is not yet defined. Here, we show that mAbs recognizing IAP can
      enhance proliferation of primary human T cells in the presence of low levels of
      anti-CD3, but have no effect on T cell proliferation on their own. Together with
      suboptimal concentrations of anti-CD3, engagement of IAP also enhances IL-2
      production in Jurkat cells, an apparently integrin-independent function of IAP.
      Nonetheless, costimulation by IAP ligation requires cell adhesion. IAP
      costimulation does not require CD28. Furthermore, anti-IAP, but not anti-CD28,
      synergizes with suboptimal anti-CD3 to enhance tyrosine phosphorylation of the
      CD3 zeta chain and the T cell-specific tyrosine kinase Zap70. Ligation of human
      IAP transfected into the hemoglobin-specific 3.L2 murine T cell hybridoma
      costimulates activation for IL-2 secretion both with anti-CD3 and with antigenic
      peptides on antigen-presenting cells (APCs). Moreover, ligation of IAP but not
      CD28 can convert antagonist peptides into agonists in 3.L2 cells. Using
      costimulation by IAP ligation as an assay to analyze the structure-function
      relationships in IAP signaling, we find that both the extracellular and multiply
      membrane-spanning domains of IAP are necessary for synergy with the antigen
      receptor, but the alternatively spliced cytoplasmic tails are not. These data
      demonstrate that IAP ligation initiates an adhesion-dependent costimulatory
      pathway distinct from CD28. We hypothesize that anti-IAP generates the
      costimulatory signal because it modulates interactions of the IgV domain with
      other plasma membrane molecules; this in turn activates effector functions of the
      multiply membrane-spanning domain of IAP. This model may have general
      significance for how IAP functions in cell activation.

PMID- 8996239
TI  - T helper subset differentiation in the absence of invariant chain.
AB  - The outcome of murine infection with Leishmania major is regulated by major
      histocompatibility complex class II-restricted T helper cells. Invariant chain
      deficient (Ii -/-) mice have impaired ability to present major histocompatibility
      complex class II-restricted antigens, and reduced numbers of CD4+ T cells.
      Despite these deficits, C57BL/6 Ii -/- mice controlled L. major infection
      comparably to wild-type mice. As assessed by mRNA analysis and in vitro antigen
      restimulation for IFN-gamma, Ii -/- mice had normal induction of Th1 subset
      differentiation even though antigen-dependent proliferation of their lymph node
      cells was substantially compromised. In addition, BALB/c Ii -/- mice exhibited a
      progressive course of infection and Th2 effector cell development that were
      comparable to that seen in wild-type BALB/c mice. We wished to determine whether
      this unexpected efficiency of T helper subset induction despite inefficient T
      cell stimulation could be modeled in vitro. In the presence of rIL-12 or rIL-4
      naive parasite-specific transgenic T cells could mature into IFN-gamma-or IL-4
      secreting T helper cells, respectively, even when antigen presentation was
      suboptimal or antigen dose was submitogenic. These experiments demonstrate that
      activation of T helper cells to a threshold required for IL-2 production or
      proliferation is not required to achieve induction of disease-regulating T helper
      cell effector functions, and that pathogen-associated secondary activation
      signals may facilitate the full differentiation of T helper subsets during
      limiting presentation of antigenic peptides.

PMID- 8996238
TI  - Secretory granule proteases in rat mast cells. Cloning of 10 different serine
      proteases and a carboxypeptidase A from various rat mast cell populations.
AB  - Two of the major rat mast cell proteases, rat mast cell protease 1 (RMCP-1) and
      RMCP-2, have for many years served as important phenotypic markers for studies of
      various aspects of mast cell (MC) biology. However, except for these proteases
      only fragmentary information has been available on the structure and complexity
      of proteases expressed by different subpopulations of rat MCs. To address these
      questions, cDNA libraries were constructed from freshly isolated rat peritoneal
      MCs and from the rat mucosal MC line RBL-1. cDNA clones for 10 different serine
      proteases (RMCP-1-10), and the MC carboxypeptidase A were isolated and
      characterized. Six of these proteases have not been isolated previously. Based on
      their protease content, three separate subpopulations of MCs were identified.
      Connective tissue MCs (CTMCs) from the ear and peritoneum express the chymases
      RMCP-1 and -5, the tryptases RMCP-6, and -7 and the carboxypeptidase A. However,
      based on a large difference in the level of expression of RMCP-7, CTMCs of these
      two organs may be regarded as two separate subpopulations. RMCP-2 and the three
      closely related proteases of the RMCP-8 subfamily were identified as the major
      mucosal MC proteases in rat. In contrast to what has been reported for human MCs,
      no expression of cathepsin G or cathepsin G-like proteases was detected in any of
      the rat MC populations. To determine mRNA frequencies for the various proteases
      expressed by normal tissue MCs, an unamplified peritoneal MC cDNA library was
      screened with a panel of mono-specific cDNA probes. These results showed that
      peritoneal MCs are highly specialized effector cells with mRNA frequencies for
      the major proteases in the range of several percent of the total mRNA pool.

PMID- 8996240
TI  - Distinct Ras effector pathways are involved in Fc epsilon R1 regulation of the
      transcriptional activity of Elk-1 and NFAT in mast cells.
AB  - Activation of Ras GTPases is a conserved feature of antigen receptor signaling,
      including Fc epsilon R1 activation of mast cells. Antigenic cross-linking of the
      Fc epsilon R1 on mast cells results in secretion of allergic mediators and
      induction of immediate early and cytokine genes. Here we examine the role of Ras
      in coupling the Fc epsilon R1 to transcriptional regulation. The transcription
      factors Elk-1, an immediate early gene regulator and the nuclear factor of
      activated T cells (NFAT), in the context of the IL-4 gene, are identified as Ras
      targets in mast cells. Ras mediates diverse effects via its diverse effector
      pathways, which may include other members of the Ras GTPase family such as RhoA
      and Rac-1. We observe that Elk-1 and NFAT are targeted by distinct Ras effector
      pathways in mast cells. Activation of the "classical" Ras/Raf-1/MEK/ ERK cascade
      is necessary and sufficient for Fc epsilon R1 induction of Elk-1. Ras function is
      required, but not sufficient for Fc epsilon R1 induction of NFAT. However,
      activation or inhibition of Ras markedly shifts the antigen dose-response for Fc
      epsilon R1 induction of NFAT. The effector pathway for Ras activation of NFAT is
      not Raf-1/MEK. We identify that the Rac-1 GTPase is critical in Fc epsilon R1
      regulation of NFAT, acting either in parallel with or as an effector of Ras.
      These data place Ras in a crucial position in mast cells, regulating disparate
      nuclear targets. Moreover, we identify that two GTPases, Ras and Rac-1, are
      important regulators of NFAT, and therefore of cytokine expression in mast cells.

PMID- 8996241
TI  - Macrophage-dependent apoptosis of CD4+ T lymphocytes from HIV-infected
      individuals is mediated by FasL and tumor necrosis factor.
AB  - Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected
      cells is observed in cell culture and in lymphoid tissue of HIV-infected
      individuals. This study addresses whether antigen-presenting cells such as human
      macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals.
      Uninfected human macrophages, and to a larger degree, HIV-infected macrophages
      mediate apoptosis of T cells from HIV-infected, but not from uninfected control
      individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T
      lymphocytes from HIV-infected individuals, and direct contact between macrophages
      and lymphocytes is required. Additional analyses indicated that the apoptosis
      inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage
      induced apoptosis of CD4+ T cells. These results support a role for macrophage
      associated FasL and TNF in the selective depletion of CD4+ T cells in HIV
      infected individuals.

PMID- 8996242
TI  - Interleukin-4 protects against a genetically linked lupus-like autoimmune
      syndrome.
AB  - Interleukin-4 (IL-4) provides support for humoral immune responses through
      upregulation of T helper (Th) type 2 cell differentiation, but it is not known
      whether IL-4 promotes antibody-mediated autoimmune diseases such as systemic
      lupus erythematosus (SLE). Here, we show that the constitutive expression of an
      IL-4 transgene by B cells completely prevents the development of lethal lupus
      like glomerulonephritis in the (NZW x C57BL/6.Yaa)F1 murine model of SLE. This
      was associated with marked changes in the serum levels of IgG subclasses, rather
      than in the total levels of anti-DNA antibodies, with a lack of IgG3, a decrease
      of IgG2a, and an increase in IgG1 subclasses, and by a strong reduction in the
      serum levels of gp70-anti-gp70 immune complexes. This effect of the transgene
      appears to result from a modulation of the Th1 versus Th2 autoimmune response,
      since the protected mice displayed comparably modified IgG2a and IgG3 antibody
      response against exogenous T cell-dependent antigen, but not against T cell
      independent antigens. Thus, IL-4 prevents the development of this lupus-like
      autoimmune disease, most likely by downregulating the appearance of Th1-mediated
      IgG subclasses of autoantibodies such as the IgG3 autoantibodies which have been
      shown to be especially nephritogenic.

PMID- 8996243
TI  - Scleroderma autoantigens are uniquely fragmented by metal-catalyzed oxidation
      reactions: implications for pathogenesis.
AB  - The observation that revelation of immunocryptic epitopes in self antigens may
      initiate the autoimmune response has prompted the search for processes which
      induce novel fragmentation of autoantigens as potential initiators of
      autoimmunity. The reversible ischemia reperfusion which characterizes scleroderma
      has focused attention on reactive oxygen species as molecules which might induce
      autoantigen fragmentation. We demonstrate that several of the autoantigens
      targeted in diffuse scleroderma are uniquely susceptible to cleavage by reactive
      oxygen species, in a metal-dependent manner. Multiple features of the
      fragmentation reaction and its inhibition indicate that these autoantigens
      possess metal-binding sites, which focus metal-catalyzed oxidation reactions (and
      consequent fragmentation) to specific regions of the antigens. These data suggest
      that the autoantibody response in scleroderma is the immune marker of unique
      protein fragmentation, induced by ischemia reperfusion in the presence of
      appropriate metals, and focus attention on abnormal metal status as a potential
      pathogenic principle in this disease.

PMID- 8996244
TI  - Membrane tumor necrosis factor (TNF) induced cooperative signaling of TNFR60 and
      TNFR80 favors induction of cell death rather than virus production in HIV
      infected T cells.
AB  - Tumor necrosis factor (TNF) and lymphotoxin (LT) are highly pleiotropic cytokines
      that play a central role in regulating HIV-1 replication. These cytokines express
      their activities through two membrane receptors, TNFR60 (p55-60) and TNFR80 (p75
      80). In the present study we have demonstrated by means of antagonistic and
      agonistic receptor-specific antibodies that in latently infected lymphocytic (ACH
      2) cells the TNFR60 plays a dominant role in signaling HIV production, although
      selective activation of TNFR80 by receptor-specific antibodies can also induce
      HIV production. Unexpectedly, when both TNFRs were activated simultaneously by
      agonistic antibodies or coculture with cells expressing a noncleavable membrane
      form of TNF, HIV production was downregulated and induction of cell death was
      enhanced in ACH-2 cells. More relevant, in vitro HIV-infected peripheral blood
      lymphocytes cocultured with cells expressing membrane TNF underwent rapid
      induction of apoptosis with a subsequent reduced HIV production of these
      lymphocytes cultures. This was not observed with HIV-infected lymphocytes treated
      with soluble TNF. These data provide evidence for the differential trigger
      potential of membrane versus soluble TNF and show that TNFR80 is an important
      modulator of TNF responsiveness of HIV-infected T cells via cooperative signaling
      with TNFR60.

PMID- 8996245
TI  - Functional inactivation in the whole population of human V gamma 9/V delta 2 T
      lymphocytes induced by a nonpeptidic antagonist.
AB  - Nonpeptidic compounds stimulate human T cells bearing the TCR-gamma delta in the
      absence of major histocompatibility complex restriction. We report that one of
      these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of V
      gamma 9/V delta T cells ex vivo, antagonizes the same cell population after
      repetitive activation. Stimulation with DPG results in partial early protein
      tyrosine phosphorylation and a prolonged, but reversible, state of
      unresponsiveness to agonist ligands in V gamma 9/V delta 2, but not in other T
      cells. These findings show that TCR antagonism is a general phenomenon of T
      cells. However, in contrast to the clonal specificity of altered peptides
      antagonizing alpha beta T cells, all the tested V gamma 9/V delta 2 polyclonal
      cell lines and clones become unresponsive, a fact that may be relevant for the
      regulation of their response in vivo.

PMID- 8996246
TI  - Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a
      structural and functional homologue of human MCP-1.
AB  - The chemokines are a large family of cytokines that control the recruitment of
      leukocytes in immune and inflammatory responses. We describe the isolation of a
      novel murine CC chemokine that, based on its biological and structural features,
      we have named monocyte chemoattractant protein (MCP)-5. MCP-5 mapped to the CC
      chemokine cluster on mouse chromosome 11 and was most closely related to human
      MCP-1 in structure (66% amino acid identity). Purified recombinant MCP-5 protein
      was a potent chemoattractant for peripheral blood monocytes, was only weakly
      active on eosinophils at high doses, and was inactive on neutrophils. MCP-5
      induced a calcium flux in peripheral blood mononuclear cells, but not in purified
      murine eosinophils or neutrophils. Consistent with these results, MCP-5 induced a
      calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and
      murine CCR2, a CC chemokine receptor expressed on monocytes. MCP-5 did not induce
      a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5.
      Constitutive expression of MCP-5 mRNA was detected predominantly in lymph nodes,
      and its expression was markedly induced in macrophages activated in vitro and in
      vivo. Moreover, MCP-5 expression was up-regulated in the lungs of mice following
      aerosolized antigen challenge of sensitized mice, and during the host response to
      infection with Nippostrongylus brasiliensis. These data indicate that MCP-5 is a
      novel and potent monocyte active chemokine that is involved in allergic
      inflammation and the host response to pathogens.

PMID- 8996247
TI  - The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor
      cells and provides a new mechanism to explain the mobilization of CD34+
      progenitors to peripheral blood.
AB  - Hematopoietic progenitor cells migrate in vitro and in vivo towards a gradient of
      the chemotactic factor stromal cell-derived factor-1 (SDF-1) produced by stromal
      cells. This is the first chemoattractant reported for human CD34+ progenitor
      cells. Concentrations of SDF-1 that elicit chemotaxis also induce a transient
      elevation of cytoplasmic calcium in CD34+ cells. SDF-1-induced chemotaxis is
      inhibited by pertussis toxin, suggesting that its signaling in CD34+ cells is
      mediated by seven transmembrane receptors coupled to Gi proteins. CD34+ cells
      migrating to SDF-1 include cells with a more primitive (CD34+/CD38- or CD34+/DR-)
      phenotype as well as CD34+ cells phenotypically committed to the erythroid,
      lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX
      progenitors. Chemotaxis of CD34+ cells in response to SDF-1 is increased by IL-3
      in vitro and is lower in CD34+ progenitors from peripheral blood than in CD34+
      progenitors from bone marrow, suggesting that an altered response to SDF-1 may be
      associated with CD34 progenitor mobilization.

PMID- 8996248
TI  - Replacement of pre-T cell receptor signaling functions by the CD4 coreceptor.
AB  - An important checkpoint in early thymocyte development ensures that only
      thymocytes with an in-frame T cell receptor for antigen beta (TCR-beta) gene
      rearrangement will continue to mature. Proper assembly of the TCR-beta chain into
      the pre-TCR complex delivers signals through the src-family protein tyrosine
      kinase p56lck that stimulate thymocyte proliferation and differentiation to the
      CD4+CD8+ stage. However, the biochemical mechanisms governing p56lck activation
      remain poorly understood. In more mature thymocytes, p56lck is associated with
      the cytoplasmic domain of the TCR coreceptors CD4 and CD8, and cross-linking of
      CD4 leads to p56lck activation. To study the effect of synchronously inducing
      p56lck activation in immature CD4-CD8- thymocytes, we generated mice expressing a
      CD4 transgene in Rag2-/- thymocytes. Remarkably, without further experimental
      manipulation, the CD4 transgene drives maturation of Rag2-/- thymocytes in vivo.
      We show that this process is dependent upon the ability of the CD4 transgene to
      bind Lck and on the expression of MHC class II molecules. Together these results
      indicate that binding of MHC class II molecules to CD4 can deliver a biologically
      relevant, Lck-dependent activation signal to thymocytes in the absence of the TCR
      alpha or -beta chain.

PMID- 8996249
TI  - Developmental regulation of VDJ recombination by the core fragment of the T cell
      receptor alpha enhancer.
AB  - The role of T cell receptor alpha enhancer (E alpha) cis-acting elements in the
      developmental regulation of VDJ recombination at the TCR alpha/delta locus was
      examined in transgenic mice containing variants of a minilocus VDJ recombination
      substrate. We demonstrate that the 116-bp T alpha 1,2 core enhancer fragment of
      the 1.4-kb E alpha is sufficient to activate the enhancer-dependent step of
      minilocus rearrangement, and that within T alpha 1,2, intact binding sites for
      TCF/LEF and Ets family transcription factors are essential. Although minilocus
      rearrangement under the control of the 1.4-kb E alpha initiates at fetal day 16.5
      and is strictly limited to alpha beta T cells, we find that rearrangement under
      the control of T alpha 1,2 initiates slightly earlier during ontogeny and occurs
      in both gamma delta and alpha beta T cells. We conclude that the core fragment of
      E alpha can establish accessibility to the recombinase in developing thymocytes
      in vivo in a fashion that is dependent on the binding of TCF/LEF and Ets family
      transcription factors, but that these and other factors that bind to the E alpha
      core cannot account for the precise developmental onset of accessibility that is
      provided by the intact E alpha. Rather, our data suggests a critical role for
      factors that bind E alpha outside of the core T alpha 1,2 region in establishing
      the precise developmental onset of TCR alpha rearrangement in vivo.

PMID- 8996250
TI  - Downregulation of CD1 marks acquisition of functional maturation of human
      thymocytes and defines a control point in late stages of human T cell
      development.
AB  - We have investigated whether in the human thymus transition of CD4+CD8+ double
      positive (DP) to CD4+ or CD8+ single positive (SP) cells is sufficient for
      generation of functional immunocompetent T cells. Using the capacity of
      thymocytes to expand in vitro in response to PHA and IL-2 as a criterion for
      functional maturity, we found that functional maturity of both SP and DP
      thymocytes correlates with downregulation of CD1a. CD1a- cells with a persistent
      DP phenotype were also found in neonatal cord blood, suggesting that at least a
      proportion of mature DP cells can emigrate from the thymus. The requirements for
      generating functional T cells were investigated in a hybrid human/mouse fetal
      thymic organ culture. MHC class II-positive, but not MHC class II-negative, mouse
      thymic microenvironments support differentiation of human progenitors into TCR
      alpha beta+CD4+ SP cells, indicating that mouse MHC class II can positively
      select TCR alpha beta +CD4+ SP human cells. Strikingly, these SP are arrested in
      the CD1a+ stage and could not be expanded in vitro with PHA and IL-2. CD1a+CD4+
      SP thymocytes do not represent an end stage population because purified CD1a+CD4+
      SP thymocytes differentiate to expandable CD1a- cells upon cocultivation with
      human thymic stromal cells. Taken together these data indicate that when CD1a+ DP
      TCR alpha beta low cells mature, these cells interact with MHC, but that an
      additional, apparently species-specific, signal is required for downregulation of
      CD1a to generate functional mature TCR alpha beta + cells.

PMID- 8996251
TI  - Loss of ATP diphosphohydrolase activity with endothelial cell activation.
AB  - Quiescent endothelial cells (EC) regulate blood flow and prevent intravascular
      thrombosis. This latter effect is mediated in a number of ways, including
      expression by EC of thrombomodulin and heparan sulfate, both of which are lost
      from the EC surface as part of the activation response to proinflammatory
      cytokines. Loss of these anticoagulant molecules potentiates the procoagulant
      properties of the injured vasculature. An additional thromboregulatory factor,
      ATP diphosphohydrolase (ATPDase; designated as EC 3.6.1.5) is also expressed by
      quiescent EC, and has the capacity to degrade the extracellular inflammatory
      mediators ATP and ADP to AMP, thereby inhibiting platelet activation and
      modulating vascular thrombosis. We describe here that the antithrombotic effects
      of the ATPDase, like heparan sulfate and thrombomodulin, are lost after EC
      activation, both in vitro and in vivo. Because platelet activation and
      aggregation are important components of the hemostatic changes that accompany
      inflammatory diseases, we suggest that the loss of vascular ATPDase may be
      crucial for the progression of vascular injury.

PMID- 8996252
TI  - Follicular dendritic cells specifically express the long CR2/CD21 isoform.
AB  - This paper describes an antibody (mAb 7D6) that specifically recognizes human
      follicular dendritic cells (FDCs). By expression cloning, a cDNA clone encoding
      for the long human CR2/ CD21 isoform (CD21L) that contains an additional exon
      (10a) was isolated. We demonstrated that FDCs selectively express CD21L, while B
      cells selectively express the short CR2/CD21 lacking exon 10a (CD21S). By
      screening mouse Ltk- cells transfected with the CD21L cDNA, we further showed
      that the other two anti-human FDC mAbs DRC-1 and KiM4 also recognize CD21L. Thus,
      CD21L represents the first characterized human FDC-specific molecule, which may
      confer unique functions of FDCs in germinal center development.

PMID- 8996253
TI  - Multiple cytokines and acute inflammation raise mouse leptin levels: potential
      role in inflammatory anorexia.
AB  - Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL
      1, induce anorexia and loss of lean body mass, common manifestations of acute and
      chronic inflammatory conditions. In C57BL/6 female mice, the administration of
      TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a
      prompt and dose-dependent increase in serum leptin levels and leptin mRNA
      expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines
      not known to induce anorexia or decrease food intake, had no effect on leptin
      gene expression or serum leptin levels. After administration of Escherichia coli
      lipopolysaccharide (LPS), leptin gene expression and leptin levels were
      increased. These findings suggest that leptin levels may be one mechanism by
      which anorexia is induced during acute inflammatory conditions.

PMID- 8996255
TI  - Medical issues and emergencies in the dermatology office.
AB  - We review the medical issues and emergencies potentially encountered in the
      practice of general or surgical dermatology. Traditional guidelines have largely
      consisted of dated extrapolations from the nondermatologic literature concerning
      procedures that are primarily irrelevant to dermatology. This article outlines a
      rational approach to organizing an office emergency plan for anaphylaxis, stroke,
      status epilepticus, myocardial infarction, and hypertensive crisis. We discuss
      the literature that has influenced current office behavior regarding endocarditis
      prophylaxis, the use of electrosurgery with pacemakers, arrhythmogenic drug
      interactions, vasovagal syncope, lidocaine "allergy," and bleeding complications
      from oral anticoagulants. Recommendations for managing these issues in a
      dermatologic context are provided.

PMID- 8996257
TI  - Childhood white superficial onychomycosis caused by Trichophyton rubrum: report
      of seven cases and review of the literature.
AB  - BACKGROUND: Although white superficial onychomycosis (WSO) is well recognized in
      adults and considered to be mainly caused by Trichophyton mentagrophytes,
      childhood WSO is rare. WSO caused by Trichophyton rubrum in prepubertal children
      has never been reported. OBJECTIVE: Our purpose was to describe the existence of
      WSO in children and to emphasize that T. rubrum may be its main cause. METHODS:
      Seven children with WSO seen between 1988 and 1993 were examined. Only patients
      who had a positive potassium hydroxide preparation and a positive fungal culture
      were included. RESULTS: Seven healthy prepubertal children, 2 to 9 years of age,
      were identified with WSO. All cases were proved to be caused by T. rubrum. Six
      patients had associated tinea pedis, and five had a family history of tinea
      pedis. Topical antifungal therapy was partially effective in some cases.
      CONCLUSION: This report documents the existence of WSO in prepubertal children.
      All cultures grew T. rubrum. Although onychomycosis is not as common in
      prepubertal children as in adults, it may be underrecognized.

PMID- 8996256
TI  - Biologic effects of topical calcipotriol (MC 903) treatment in psoriatic skin.
AB  - BACKGROUND: The biologically active vitamin D analog calcipotriol is effective
      and safe in the topical treatment of psoriasis, but its exact mechanism of action
      is unknown. OBJECTIVE: We investigated expression of 1,25-dihydroxyvitamin D3
      receptors, markers for inflammation (CD1a, CD4, CD8, CD11b, CD15; NAP
      1/interleukin-8; 55 kd tumor necrosis factor-receptor; intercellular adhesion
      molecule-1; HLA-DR), proliferation (proliferating cell nuclear antigen, Ki-67),
      and differentiation (transglutaminase K; involucrin; cytokeratin 16) in psoriatic
      skin during topical calcipotriol treatment. METHODS: For immunohistochemical
      staining we used the labeled avidin-biotin technique on cryostat-cut sections.
      RESULTS: We found a significant increase of 1,25-dihydroxyvitamin D3 receptor
      expression in epidermal basal keratinocytes of lesional psoriatic skin during
      calcipotriol treatment. In all patients analyzed, effects on proliferation and
      differentiation of epidermal keratinocytes were stronger than effects on dermal
      inflammation. Effects on inflammation were more pronounced in the epidermal than
      in the dermal compartment. CONCLUSION: Our findings indicate that analogs of 1,25
      dihydroxyvitamin D3 upregulate their corresponding receptor in human
      keratinocytes in vivo. This mechanism may be important in the therapeutic
      efficacy of vitamin D analogs in psoriasis. The differential therapeutic effects
      in the epidermal and dermal skin compartments may be due to a reduced
      bioavailability of calcipotriol in the dermal compartment.

PMID- 8996254
TI  - CD80 costimulation is essential for the induction of airway eosinophilia.
AB  - CD80 and CD86 (B7-1 and B7-2) are the ligands on antigen-presenting cells (APCs)
      which bind CD28 and deliver the costimulatory signals necessary for T cell
      activation. The reasons for the existence of two CD28 binding molecules are not
      well understood. We created a mutant version of CTLA4-Ig that could selectively
      bind CD80 and block CD28-CD80 interaction but leave CD28-CD86 binding intact.
      CD80 blockade prevented antigen-induced accumulation of eosinophils and
      lymphocytes in the lung of immunized mice, but did not block antigen induced
      systemic blood eosinophilia or IgE antibody production. No preferential
      expression of CD80 could be demonstrated on a population of lung APC consisting
      mainly of macrophages. These results indicate that CD80 costimulation is not
      necessary for the induction of Th2 immune responses but rather for the
      maintenance or amplification of lung inflammatory responses.

PMID- 8996258
TI  - Community perceptions about the important signs of early melanoma.
AB  - BACKGROUND: Detecting melanoma early often relies on patient concern about a
      particular pigmented lesion. However, it is not clear what specific features the
      public views as being important. OBJECTIVE: Our purpose was to explore the
      importance persons place on various features of skin lesions when looking for
      early signs of melanoma. METHODS: This study comprised 1148 respondents
      (participation rate, 78%) from 60 rural communities in Queensland, Australia, who
      participated in a telephone interview. RESULTS: The following features were
      considered important and are listed in order of importance: change in the lesion
      (clearly identified as the most important), more than one color, uneven edges,
      elevation, large size (the last three of equal importance), and hairiness of the
      lesion. Age, sex, education, self-efficacy, perceived knowledge, and recent self
      examination influenced importance levels, but having a recent skin examination by
      a family physician did not. CONCLUSION: To increase the skin self-examination
      skills of the community, guidelines may have to become more specific and all
      opportunities fully utilized to educate the public.

PMID- 8996259
TI  - Human protoporphyria: reduced cutaneous photosensitivity and lower erythrocyte
      porphyrin levels during pregnancy.
AB  - BACKGROUND: Women with erythropoietic protoporphyria (EPP) have reported
      increased sunlight tolerance during pregnancy. Review of clinical information in
      an existing database for an EPP population study found five women who had six
      pregnancies while enrolled. All had experienced attenuated photosensitivity
      during gestation. OBJECTIVE: Our purpose was to gain insight into whether altered
      porphyrin metabolism during pregnancy might explain this phenomenon. METHODS:
      Erythrocyte protoporphyrin levels obtained for these women during six periods of
      gestation were compared with data accumulated over the course of several years
      during nongestational periods. RESULTS: Erythrocyte porphyrin levels were lower
      during pregnancy. The differences of the means for values obtained during
      nongestational periods versus values obtained during pregnancy for each woman
      were found to reach or approach significance (p < 0.05) by a paired t test when
      analyzed without regard for seasonality (p = 0.042) or when adjusted for possible
      seasonal effects of sunlight on erythrocyte porphyrin levels by separation into
      data sets for low sunlight months (October-April) (p = 0.039) or high sunlight
      months (May-September) (p = 0.057). CONCLUSION: These observations suggest that a
      beneficial physiologic effect of pregnancy in patients with EPP may be a lower
      circulating erythrocyte protoporphyrin burden that leads to reduced
      photosensitivity.

PMID- 8996260
TI  - Circulating pemphigus IgG in families of patients with pemphigus: comparison of
      indirect immunofluorescence, direct immunofluorescence, and immunoblotting.
AB  - BACKGROUND: Patients with pemphigus vulgaris (PV) are genetically linked to two
      alleles of the HLA subgroup, and circulating antibodies were found in first
      degree relatives of these patients, thus showing genetic predisposition.
      OBJECTIVE: Our purpose was to determine the occurrence of circulating true PV-IgG
      in patients' relatives. METHODS: Circulating PV-IgG was determined in 21 first
      degree relatives of 12 patients with PV by indirect immunofluorescence on monkey
      esophagus, carcinoma A431 cultures, and Western immunoblotting. Direct
      immunofluorescence was performed on skin biopsy specimens of 20 relatives.
      RESULTS: Circulating PV-IgG was detected in 15 relatives (71%) by all methods
      tested. Good correlation was found between immunoblot reactivity and
      immunofluorescence. Of the 15 "positive" relatives, only five showed fixation of
      IgG to epidermal cells in vivo. CONCLUSION: The permeability of the epidermis or
      epidermal cell reactivity in vivo probably controls the expression of disease in
      patients' relatives.

PMID- 8996261
TI  - A comparative study of three occlusive dressings in the treatment of full
      thickness wounds in pigs.
AB  - BACKGROUND: Little objective information is available on the influence of
      occlusive dressings on the healing of cutaneous full-thickness wounds. OBJECTIVE:
      Our purpose was to examine the effects of three occlusive dressings-two
      hydrocolloid dressings (Comfeel Ulcer Dressing, Coloplast A/S, Espergaerder,
      Denmark [hydrocolloid dressing A] and DuoDERM; ConvaTec, Princeton, N.J.
      [hydrocolloid dressing B]) and one polyurethane film dressing (OpSite, Smith &
      Nephew, Hull, U.K. [film dressing])-on tissue reactions, degree of inflammation,
      wound contraction, and epithelialization in full-thickness wounds in domestic
      pigs. METHODS: Standardized 20 mm full-thickness punch biopsy wounds were treated
      for 10 days. Healing was assessed by light microscopy and by planimetry. RESULTS:
      Material from both hydrocolloid dressings was phagocytosed as indicated by the
      presence of foam cells in the granulation tissue. Granulomatous tissue reactions
      around extracellular vacuoles were found in 10 of 12 hydrocolloid dressing B
      treated wounds compared with one in hydrocolloid dressing A-treated wounds and in
      none of the 10 film dressing-treated wounds (p < 0.0001). Inflammation was
      significantly (p < 0.002) more pronounced in hydrocolloid dressing B-treated
      wounds. The extracellular vacuoles in the hydrocolloid dressing B group contained
      dressing material as demonstrated by Fourier transform infrared microscopy. There
      was a tendency (p < 0.07) towards a delayed entry into the contraction phase with
      hydrocolloid dressing B, but there was no significant difference in
      epithelialization between the three dressings. CONCLUSION: Wound tissue reactions
      to different hydrocolloid dressings vary depending on composition. The tissue
      reactions had no significant effect on wound contraction or epithelialization.

PMID- 8996262
TI  - Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen
      planopilaris.
AB  - BACKGROUND: Lichen planopilaris usually produces multifocal areas of scarring
      alopecia. Recently, a condition in postmenopausal women characterized by
      progressive frontal hairline recession associated with scarring has been
      described. OBJECTIVE: Our purpose was to study the clinical and histopathologic
      features and results of treatment in a group of women with the frontal variant of
      lichen planopilaris and to compare the immunohistochemical profile of scalp
      biopsy specimens from this subset with that found in the multifocal variant of
      lichen planopilaris. METHOD: The clinical data as well as the histopathologic
      findings in 16 women with frontal fibrosing alopecia were collated. The
      immunohistochemical profile of six scalp biopsy specimens from the frontal
      hairline were compared with six specimens from women with multifocal lichen
      planopilaris. RESULTS: In addition to the progressive frontal fibrosing alopecia
      in all 16 women, total loss or a marked decrease of the eyebrows was observed in
      13. No evidence of lichen planus was observed at other sites. In one patient
      multifocal areas of lichen planopilaris developed in the scalp. The frontal
      fibrosing alopecia was slowly progressive but has stabilized in five patients.
      Biopsy specimens from the frontal hairline showed histologic changes identical to
      lichen planopilaris. Immunophenotyping failed to reveal any significant
      differences between the frontal and multifocal variants. No effective treatments
      emerged although oral steroids and antimalarials may temporarily slow the course.
      Hormone replacement therapy did not appear to influence the course of the
      alopecia. CONCLUSION: Progressive frontal fibrosing alopecia is a clinically
      distinct variant of lichen planopilaris that affects in particular elderly women
      and frequently involves the eyebrows. The basis for this lichenoid tissue
      reaction targeting frontal scalp follicles and eyebrows is unknown.

PMID- 8996263
TI  - Low-dose methotrexate administered weekly is an effective corticosteroid-sparing
      agent for the treatment of the cutaneous manifestations of dermatomyositis.
AB  - BACKGROUND: The cutaneous manifestations of dermatomyositis can be the most
      prominent finding and are often difficult to treat. OBJECTIVE: Our purpose was to
      determine whether low-dose methotrexate administered weekly in combination with
      other systemic therapies or as a sole systemic agent is effective in the
      treatment of the cutaneous disease in patients with dermatomyositis. METHODS: We
      reviewed the records of 13 patients who received oral methotrexate in doses
      ranging from 2.5 to 30 mg weekly. Their skin lesions had not been completely
      responsive to sunscreens, topical corticosteroids, oral prednisone, oral
      antimalarial therapy, and, in one patient each, chlorambucil and azathioprine.
      RESULTS: At the end of the study period, 4 of these 13 patients were free of all
      cutaneous manifestations of dermatomyositis, and another four had almost complete
      clearing. In the remaining five patients, methotrexate induced moderate clearing
      of their cutaneous lesions. In all patients, the addition of methotrexate allowed
      reduction or discontinuation of other therapies such as prednisone. All patients
      tolerated the methotrexate with minimal toxicity. CONCLUSIONS: Low-dose oral
      methotrexate administered weekly is effective in treatment of the cutaneous
      manifestations of dermatomyositis and frequently enables a reduction or
      discontinuation of corticosteroid therapy.

PMID- 8996265
TI  - The classification of psoriatic arthritis: what will happen in the future?
AB  - Some patients with psoriasis have articular involvement that falls within the
      spectrum of seronegative spondyloarthropathies. This form of arthritis has been
      classified by Moll and Wright into five clinical subsets. Recently this
      classification has been contested. We review the historical evolution of the
      concept of psoriatic arthritis and discuss its clinical spectrum.

PMID- 8996264
TI  - Nonsurgical treatment of basal cell carcinomas with intralesional 5
      fluorouracil/epinephrine injectable gel.
AB  - BACKGROUND: To develop a nonsurgical treatment alternative for basal cell
      carcinomas (BCCs), we evaluated intralesional sustained-release chemotherapy with
      5-fluorouracil/epinephrine injectable gel (5-FU/epi gel). OBJECTIVE: To optimize
      the dose and treatment schedule, we compared the safety, tolerance, and efficacy
      of six treatment regimens of 5-FU/epi gel in patients with BCCs. METHODS: Two
      doses and four treatment schedules of 5-FU/epi gel were compared in an open
      label, randomized study of 122 patients with biopsy-proven BCCs. One BCC per
      patient was treated for up to 4 to 6 weeks, then observed for 3 months at which
      time the tumor site was completely excised for histologic examination. RESULTS:
      Overall, 91% of evaluable treated tumors (106 of 116) in all regimens had
      histologically confirmed complete tumor resolution. No clinically significant
      treatment-related systemic adverse events occurred. The best response rate,
      tolerance, and patient compliance with assigned dose were in patients receiving
      0.5 ml of 5-FU/epi gel three times a week for 2 weeks. The complete response rate
      based on histologic assessment in this group was 100%. CONCLUSION: Results
      demonstrate that treatment of BCC with 5-FU/epi gel is both safe and effective,
      may result in histologically confirmed complete response rates comparable to
      surgery, and provides a nonsurgical treatment alternative in selected patients.

PMID- 8996266
TI  - Photosensitivity diseases.

PMID- 8996267
TI  - Surgical pearl: use of a double razor blade to obtain stratum corneum specimens
      for potassium hydroxide examination.

PMID- 8996268
TI  - Surgical pearl: bacteriostatic sodium chloride injection USP 0.9%.

PMID- 8996270
TI  - Erythema induratum of Bazin as a tuberculid: confirmation of Mycobacterium
      tuberculosis DNA polymerase chain reaction analysis.

PMID- 8996269
TI  - Cutaneous localization of chronic lymphocytic leukemia at the site of chickenpox.

PMID- 8996271
TI  - Treatment of 16 patients with bullous pemphigoid with oral tetracycline and
      niacinamide and topical clobetasol.

PMID- 8996272
TI  - Cutaneous infiltration in acute promyelocytic leukemia.

PMID- 8996273
TI  - Hyperimmunoglobulinemia E syndrome in HIV infection.

PMID- 8996274
TI  - Trichilemmal carcinoma.

PMID- 8996275
TI  - Cryptococcal cellulitis in an immunocompetent host.

PMID- 8996276
TI  - Stevens-Johnson syndrome associated with topical nitrogen mustard therapy.

PMID- 8996277
TI  - Systemic cyclosporine and low-dose prednisone in the treatment of chronic severe
      alopecia areata: a clinical and immunopathologic evaluation.

PMID- 8996278
TI  - Metastasis in an electrodesiccation and curettage scar.

PMID- 8996279
TI  - Treatment of aquagenic urticaria with PUVA and astemizole.

PMID- 8996280
TI  - Familial presenile sebaceous gland hyperplasia.

PMID- 8996282
TI  - Carville: 100 years of excellence.

PMID- 8996281
TI  - Laser treatment of tattoos: a prospective, paired, comparison study of the Q
      switched Nd:YAG (1064 nm), frequency-doubled Q-switched Nd:YAG (532 nm), and Q
      switched ruby lasers.

PMID- 8996283
TI  - The 19th World Congress of Dermatology, Sydney, Australia, June 15-21, 1997. Look
      back! Look around! Look forward!

PMID- 8996284
TI  - Superficial papillary adenomatosis of the nipple.

PMID- 8996285
TI  - Clinical and histologic spectrum of human T-cell lymphotropic virus type I
      associated lymphoma involving the skin.

PMID- 8996286
TI  - Scabies in HTLV-I seropositive patients.

PMID- 8996287
TI  - Estrogen replacement therapy after coronary angioplasty in women.
AB  - OBJECTIVES: The purpose of this study was to assess the effects of estrogen
      replacement therapy on long-term outcome, including restenosis, myocardial
      infarction, stroke and death after a first percutaneous transluminal coronary
      angioplasty (PTCA) procedure, in postmenopausal women. BACKGROUND: Observational
      and epidemiologic studies, basic laboratory research and clinical trials
      consistently suggest that estrogen replacement therapy is associated with
      beneficial cardiovascular effects in women. These cardioprotective actions may be
      particularly relevant to women with coronary artery disease, such as those who
      have undergone PTCA. METHODS: This was a retrospective study that included 337
      women who underwent elective PTCA between 1982 and 1994. The treatment group
      consisted of 137 consecutive women receiving long-term estrogen therapy at the
      time of elective PTCA and during follow-up. The control group comprised 200 women
      who were computer-matched with the estrogen group. The mean follow-up period was
      65 +/- 35 months. RESULTS: Actuarial survival was superior in the estrogen group;
      the 7-year survival rate was 93% for the estrogen group versus 75% for the
      control group (p = 0.001). The cardiovascular event rate (death, nonfatal
      myocardial infarction or nonfatal stroke) was significantly lower in the estrogen
      group at 7 years (12% vs. 35% in the control group, p = 0.001). The need for
      subsequent revascularization during follow-up was similar in the two groups.
      Multivariable analysis identified diabetes, estrogen therapy (adjusted risk ratio
      0.38, 95% confidence interval 0.19 to 0.79) and left ventricular ejection
      fraction < 40% as independent correlates of cardiovascular death or myocardial
      infarction during follow-up. CONCLUSIONS: Estrogen replacement therapy was
      associated with an improved long-term outcome after PTCA in postmenopausal women.

PMID- 8996288
TI  - Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary
      stenting without anticoagulation: frequency, predictors and clinical outcome.
AB  - OBJECTIVES: This study was performed to determine predictors of subacute stent
      thrombosis (SST) in the era of intravascular ultrasound (IVUS)-guided coronary
      stenting without anticoagulation. BACKGROUND: The incidence of stent thrombosis
      has declined with the application of high pressure stent deployment with only
      antiplatelet therapy. However, no data are available on predictors of stent
      thrombosis in this era. METHODS: Between March 30, 1993 and July 31, 1995, 1,042
      consecutive patients underwent coronary stenting without anticoagulation. For
      this analysis, we excluded patients who underwent coronary artery bypass surgery,
      died or had acute stent thrombosis within the 1st 24 h after stenting (41
      patients). A total of 1,001 patients (1,334 lesions) were included; 982 patients
      (1,315 lesions) without SST and 19 patients (19 lesions) with SST. RESULTS: The
      rate of SST was 1.9% (per patient). There was no difference between the SST and
      No SST groups in rescue stenting (12% vs. 13.5%, p = 1.0) or mean +/- SD
      reference diameter (3.11 +/- 0.58 vs. 3.19 +/- 0.53 mm, p = 0.54). A preexisting
      thrombus was present in 12% of the SST group and in 4.5% of the No SST group (p =
      0.19). Predictors of SST by univariate analysis were low ejection fraction (p =
      0.004), more stents per lesion (p = 0.049), use of combination of different
      stents (p = 0.012), smaller balloon size (p = 0.012) and suboptimal result in
      terms of smaller lumen dimensions by angiography (p = 0.016) and IVUS (p =
      0.004), residual dissections (p = 0.027) and slow flow (p = 0.0001). In stepwise
      logistic regression analysis, ejection fraction (p = 0.019), use of a combination
      of different stents (p = 0.013) and postprocedure dissections (p = 0.014) and
      slow flow (p = 0.0001) were predictive of SST. CONCLUSIONS: In the present era of
      stent implantation, factors that may predispose to SST are low ejection fraction,
      intraprocedural complications leading to utilization of more stents, particularly
      with different stent designs, and suboptimal final result in terms of smaller
      lumen dimensions and persistent slow flow and dissections.

PMID- 8996290
TI  - High pressure assisted coronary stent implantation accomplished without
      intravascular ultrasound guidance and subsequent anticoagulation.
AB  - OBJECTIVES: The purpose of this study was to determine the efficacy of treatment
      with antiplatelet therapy and no anticoagulation after high pressure assisted
      coronary stent implantation performed without intravascular ultrasound (IVUS)
      guidance. BACKGROUND: Previous studies have shown that during IVUS-guided Palmaz
      Schatz coronary stenting, it is safe to withhold anticoagulation when stent
      expansion has been optimized by high pressure balloon dilation. METHODS: Patients
      that had successful coronary stenting without IVUS guidance were treated with
      ticlopidine, 500 mg/day, and aspirin, 325 mg/day, for 1 month and then received
      only aspirin, 325 mg/day, indefinitely. Patients were not treated with warfarin
      (Coumadin) or heparin after successful stenting. Clinical and angiographic events
      were assessed at 1 month. RESULTS: A total of 201 intracoronary stents were
      implanted in 127 patients with 137 lesions. The average number of stents per
      lesion was 1.4 +/- 0.8, and the average number of stents per patient was 1.6 +/-
      1.1. Stent deployment was performed for elective indications in 79% of procedures
      and for emergency indications in 21%. There were four stent thrombosis events for
      a per patient event rate of 3.1% and a per lesion event rate of 2.9%.
      CONCLUSIONS: After high pressure assisted stenting performed without IVUS
      guidance, there was an acceptable incidence of 3.1% of stent thrombosis with the
      combination of short-term ticlopidine and aspirin therapy and no anticoagulation.
      Although the study involved only 127 patients, the results support the relative
      safety of stenting without IVUS guidance and with antiplatelet therapy only in
      comparison to historical trials on stenting performed with postprocedure
      anticoagulation.

PMID- 8996289
TI  - Ticlopidine and aspirin pretreatment reduces coagulation and platelet activation
      during coronary dilation procedures.
AB  - OBJECTIVES: It is unknown whether a therapeutic combination of aspirin (ASA) and
      ticlopidine might effectively decrease activation of hemostasis. BACKGROUND:
      Percutaneous transluminal coronary angioplasty (PTCA), rotational atherectomy and
      stent implantation are procedures that fracture or ablate endothelium and plaque,
      a situation that activates hemostasis. METHODS: In 85 patients undergoing PTCA
      for a 77.8 +/- 1% stenosis, we measured markers of coagulation and platelet
      activation (thrombin-antithrombin complexes [TAT], prothrombin fragment 1 + 2 [F1
      + 2] serotonin and the presence of circulating activated platelets reacting with
      monoclonal antibodies against glycoproteins exposed on platelet membranes). Blood
      samples were drawn from a peripheral vein and from the coronary ostium before the
      procedures. Both immediately and 10 min after angioplasty, and 10 min afterward,
      samples were collected from a probing catheter (0.018 in, [0.46 cm]) positioned
      beyond the stenosis. All patients were being treated with antianginal drugs and
      ASA, 250 mg/day. Seventy of them had taken ticlopidine, 250 mg, twice daily for <
      or = 1 day (< or = 24 h) (n = 28) or for > or = 3 days (> or = 72 h) (n = 42).
      Heparin (150 U/kg) was administered before angioplasty. Thirty patients underwent
      PTCA; 15 of them were not treated with ticlopidine and 15 were given ticlopidine
      (> or = 72 h). Thirty-five patients had stent implantation, 20 rotational
      atherectomy. RESULTS: Before and during the procedures, there was greater
      thrombin generation (expressed by higher TAT and F1 + 2 plasma levels) in
      patients not taking ticlopidine or taking it for < or = 24 h (p < 0.05). Platelet
      activation and plasma serotonin levels were also significantly higher in the no
      ticlopidine or < or = 24-h ticlopidine groups. CONCLUSIONS: The combined use of
      ticlopidine, ASA and heparin effectively controls activation of coagulation in
      patients with stable or unstable angina undergoing coronary dilation.

PMID- 8996291
TI  - Coronary stent placement in patients with acute myocardial infarction: comparison
      of clinical and angiographic outcome after randomization to antiplatelet or
      anticoagulant therapy.
AB  - OBJECTIVES: The Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial is
      a randomized comparison of combined antiplatelet with anticoagulant therapy after
      coronary Palmaz-Schatz stent placement. The objective of this study was to
      compare early and late clinical and angiographic outcome in a subgroup of
      patients with stent placement for acute myocardial infarction. BACKGROUND:
      Stenting has become a treatment option for acute myocardial infarction, but it is
      not known which antithrombotic regimen is more adequate after stent implantation.
      METHODS: One hundred twenty-three patients with successful stenting after acute
      myocardial infarction were randomized to receive aspirin plus ticlopidine (n =
      61) or intense anticoagulant therapy (n = 62). Six-month repeat angiography was
      performed in 101 (86.3%) eligible patients. RESULTS: During the first 30 days
      after stenting, patients with antiplatelet therapy had a significantly lower
      clinical event rate (3.3% vs. 21.0%, p = 0.005) and stent vessel occlusion rate
      (0% vs. 9.7%, p = 0.03) and a trend to fewer cardiac events (1.6% vs. 9.7%, p =
      0.12). After 6 months, the survival rate free of recurrent myocardial infarction
      was higher in patients with antiplatelet therapy (100% vs. 90.3%, p = 0.03), and
      the rate of stent vessel occlusion was lower (1.6% vs. 14.5%, p = 0.02). Both
      groups had comparable restenosis rates (26.5% vs. 26.9%, p = 0.87). CONCLUSIONS:
      This study demonstrates that combined antiplatelet therapy after stent placement
      in patients with acute myocardial infarction is associated with an overall better
      clinical and angiographic outcome than anticoagulant therapy.

PMID- 8996293
TI  - Troponin T identifies patients with unstable coronary artery disease who benefit
      from long-term antithrombotic protection. Fragmin in Unstable Coronary Artery
      Disease (FRISC) Study Group.
AB  - OBJECTIVES: We sought to evaluate whether troponin T might be used for
      identification of patients with unstable coronary artery disease in whom
      treatment with low molecular weight heparin is beneficial. BACKGROUND: Early
      identification of subgroups with differences in response to a certain treatment
      is important to optimize the utilization of different therapeutic approaches.
      METHODS: Nine-hundred seventy-one patients with unstable coronary artery disease
      who participated in a trial of the low molecular weight heparin dalteparin
      (Fragmin) and who provided blood samples were classified into subgroups according
      to troponin T level. In the short-term phase all patients received subcutaneous
      dalteparin/placebo twice daily for 6 days. During the long-term phase they
      continued with daltparin/placebo once daily for another 5 weeks. RESULTS: In the
      short-term phase, dalteparin reduced the incidence of death or myocardial
      infarction from 2.4% to 0% (p = 0.12) and from 6.0% to 2.5% (p < 0.05) in 327 and
      644 patients with troponin T levels < 0.1 and > or = 0.1 micrograms/liter,
      respectively. During long-term treatment there was an increasing difference
      between the placebo and dalteparin group in those with troponin T levels > or =
      0.1 microgram/liter, in whom the incidences at 40 days were 14.2% and 7.4%,
      respectively (p < 0.01). In contrast, no beneficial effect of the long-term
      treatment could be demonstrated in those with troponin T levels < 0.1
      microgram/liter (4.7% vs. 5.7%). CONCLUSIONS: Elevation of troponin T identifies
      a subgroup of patients in whom prolonged antithrombotic treatment (e.g., with
      dalteparin) is beneficial.

PMID- 8996292
TI  - Gender and acute myocardial infarction: is there a different response to
      thrombolysis?
AB  - OBJECTIVES: This study sought to 1) determine the effect of gender on early and
      late infarct-related artery patency and reocclusion after thrombolytic therapy
      for acute myocardial infarction; 2) examine the effect of gender on left
      ventricular function in response to injury/reperfusion; and 3) assess the
      independent contribution of gender to early (30-day) mortality after acute
      myocardial infarction. BACKGROUND: Women have a higher mortality rate than men
      after myocardial infarction. However, the effect of gender on infarct-related
      coronary artery patency and left ventricular response to injury/reperfusion have
      not been fully defined in the thrombolytic era. METHODS: Patency rates and global
      and regional left ventricular function were determined in patients at 90 min and
      5 to 7 days after thrombolytic therapy for acute myocardial infarction. The
      effect of gender on infarct-related artery patency and left ventricular function
      was determined. Thirty-day mortality differences between women and men were
      compared. RESULTS: Women were significantly older and had more hypertension,
      diabetes, hypercholesterolemia, heart failure and shock. They were less likely to
      have had a previous myocardial infarction, history of smoking or previous bypass
      surgery. Ninety-minute patency rates (Thrombolysis in Myocardial Infarction
      [TIMI] flow grade 3) in women and men were 39% and 38%, respectively (p = 0.5).
      Reocclusion rates were 8.7% in women versus 5.1% in men (p = 0.14). Women had
      more recurrent ischemia than men (21.4% vs. 17.0%, respectively, p = 0.01).
      Ninety-minute ejection fraction and regional ventricular function were clinically
      similar in women and men with TIMI 2 or 3 flow (ejection fraction [mean +/- SD]:
      63.4 +/- 6% vs. 59.4 +/- 0.7%, p = 0.02; number of chords: 21.4 +/- 0.9 vs. 21.0
      +/- 1.9, p = 0.7; SD/chord: -2.4 +/- 08 vs. -2.4 +/- 0.2, p = 0.9, respectively).
      No clinically significant differences in left ventricular function were noted at
      5- to 7-day follow-up. Women had a greater hyperkinetic response than men in the
      noninfarct zone (SD/chord: 2.4 +/- 0.2 vs. 1.7 +/- 0.1, p = 0.005). The 30-day
      mortality rate was 13.1% in women versus 4.8% in men (p < or = 0.0001). After
      adjustment for other clinical and angiographic variables, gender remained an
      independent determinant of 30-day mortality. CONCLUSIONS: Women do not differ
      significantly from men with regard to either early infarct-related artery patency
      rates or reocclusion after thrombolytic therapy or ventricular functional
      response to injury/reperfusion. Gender was an independent determinant of 30-day
      mortality after acute myocardial infarction.

PMID- 8996294
TI  - Angiotensin-converting enzyme inhibitor therapy affects left ventricular mass in
      patients with ejection fraction > 40% after acute myocardial infarction.
AB  - OBJECTIVES: We tested the hypothesis that angiotensin-converting enzyme (ACE)
      inhibitor therapy decreases left ventricular (LV) mass in patients with a left
      ventricular ejection fraction (LVEF) > 40% and no evidence of heart failure after
      their first acute Q wave myocardial infarction (MI). BACKGROUND: Recently, ACE
      inhibitor therapy has been shown to have an early mortality benefit in unselected
      patients with acute MI, including patients without heart failure and a LVEF >
      35%. However, the effects on LV mass and volume in this patient population have
      not been studied. METHODS: Thirty-five patients with a LVEF > 40% after their
      first acute Q wave MI were randomized to titrated oral ramipril (n = 20) or
      conventional therapy (control, n = 15). Magnetic resonance imaging (MRI)
      performed an average of 7 days and 3 months after MI provided LV volumes and mass
      from summated serial short-axis slices. RESULTS: Left ventricular end-diastolic
      volume index did not change in ramipril-treated patients (62 +/- 16 [SD] to 66 +/
      17 ml/m2) or in control patients (62 +/- 16 to 68 +/- 17 ml/m2), and stroke
      volume index increased significantly in both groups. However, LV mass index
      decreased in ramipril-treated patients (82 +/- 18 to 73 +/- 19 g/m2, p = 0.0002)
      but not in the control patients (77 +/- 15 to 79 +/- 23 g/m2). Systolic arterial
      pressure did not change in either group at 3-month follow-up. CONCLUSIONS: In
      patients with a LVEF > 40% after acute MI, ramipril decreased LV mass, and blood
      pressure and LV function were unchanged after 3 months of therapy. Whether the
      decrease in mass represents a sustained effect that is associated with a decrease
      in morbid events requires further investigation.

PMID- 8996296
TI  - Assessment of myocardial viability in chronic coronary artery disease using
      technetium-99m sestamibi SPECT. Correlation with histologic and positron emission
      tomographic studies and functional follow-up.
AB  - OBJECTIVES: The value of 99mTc-sestamibi (2-methoxy-isobutyl isonitrile [MIBI])
      as a viability tracer was investigated in patients undergoing coronary artery
      bypass graft surgery. BACKGROUND: Initial studies claim that rest MIBI single
      photon emission computed tomographic (SPECT) studies can be used to assess
      myocardial viability. METHODS: Thirty patients with a severely stenosed left
      anterior descending coronary artery and wall motion abnormalities were
      prospectively included. The patients underwent a MIBI rest study, a positron
      emission tomographic (PET) flow (13NH3) and metabolism (18F-deoxyglucose) study
      and nuclear angiography before undergoing bypass surgery. A preoperative
      transmural biopsy specimen was taken from the left ventricular anterior wall.
      Morphometry was performed to assess percent fibrosis. After 3 months,
      radionuclide angiography was repeated. RESULTS: Statistically significant higher
      MIBI values were found in the group with myocardial viability as assessed by PET
      than in the group with PET-assessed nonviability (p < 0.01). Significantly higher
      MIBI values were found in the group with enhanced contractility at 3 months (76
      +/- 13% vs. 53 +/- 22%, p < 0.01). A linear relation was found between MIBI
      uptake and percent fibrosis in the biopsy specimen (r = 0.78, p < 0.00001). When
      maximizing the threshold for assessment of viability with MIBI by using
      functional improvement as the reference standard, a cutoff value of 50% was
      found, with positive and negative predictive values of 82% and 78%, respectively.
      CONCLUSIONS: 99mTc MIBI uptake was significantly higher in PET-assessed viable
      areas and in regions with enhanced contractility at 3 months. A linear relation
      was found between percent fibrosis and MIBI uptake. An optimal threshold of 50%
      was found for prediction of functional recovery.

PMID- 8996295
TI  - Evaluation of patterns of perfusion and metabolism in dobutamine-responsive
      myocardium.
AB  - OBJECTIVES: We investigated the patterns of perfusion and metabolism in
      dysfunctional myocardium whose contractility improved with dobutamine.
      BACKGROUND: Clinical studies have suggested that dobutamine echocardiography can
      identify hibernating myocardium, but laboratory studies suggest that reduced
      perfusion limits the response to dobutamine. METHODS: Twenty-five patients with
      coronary disease and ventricular dysfunction underwent low (5 and 10
      micrograms/kg body weight per min) and high dose (maximum of 50 micrograms/kg per
      min) dobutamine echocardiography and positron emission tomography (PET) using
      nitrogen-13 (N-13) ammonia and fluorine-18 fluorodeoxyglucose (FDG) for imaging
      of perfusion and metabolism. Wall motion and tracer uptake were scored in 16 left
      ventricular segments. RESULTS: Perfusion and metabolism were normal in 56.4%,
      mildly reduced in 29.1% and mismatched (reduced perfusion, preserved FDG uptake)
      in 14.5% of dysfunctional segments viable on PET. Wall motion improved with
      dobutamine in 89 dysfunctional segments (62 at low dose, 27 only at peak dose),
      and 86 of these (97%) were viable on PET. Improvement in wall motion with
      dobutamine was more common in segments with normal perfusion and metabolism
      (56.5%) than in those with mildly reduced tracer uptake (28.5%, p < 0.001) and
      those with mismatch (32%, p = 0.03). All the segments with a biphasic response
      were supplied by vessels with > or = 70% stenosis, and 88% had normal perfusion
      and metabolism. CONCLUSIONS: The majority of viable segments with rest
      dysfunction had normal perfusion and metabolism, suggesting that myocardial
      stunning was common. Improvement of wall motion at low and high doses of
      dobutamine was highly correlated with myocardial viability on PET and was more
      common in myocardium with normal perfusion. A biphasic response to dobutamine
      identified segments with normal perfusion and metabolism supplied by severely
      diseased vessels.

PMID- 8996297
TI  - Comparative diagnostic accuracy of Tl-201 and Tc-99m sestamibi SPECT imaging
      (perfusion and ECG-gated SPECT) in detecting coronary artery disease in women.
AB  - OBJECTIVES: This prospective study was conducted in 115 women to directly compare
      the sensitivity and specificity of thallium-201 (Tl-201), technetium-99m (Tc-99m)
      sestamibi perfusion and Tc-99m sestamibi electrocardiographic (ECG)-gated single
      photon emission computed tomographic (SPECT) studies for detection of coronary
      artery disease (CAD). BACKGROUND: Data on the comparative diagnostic accuracy of
      Tl-201 and Tc-99m sestamibi perfusion imaging for the detection of CAD,
      specifically in women, are very limited. METHODS: Eighty-five patients with
      suspected CAD, scheduled for coronary angiography, and 30 volunteers with a
      pretest likelihood of < or = 5% for CAD were evaluated. Within 1 week, each
      patient underwent Tl-201 and Tc-99m sestamibi SPECT imaging procedures (both
      perfusion and gated SPECT imaging). Treadmill stress testing was used in 78
      patients and dipyridamole in the remaining 37 patients. All images were
      interpreted by three observers in a blinded manner (consensus reading).
      Technetium-99m sestamibi SPECT studies were read without and then with ECG
      gating. Technetium-99m sestamibi gated SPECT studies were used to differentiate
      scar tissue from soft tissue attenuation artifact. RESULTS: The overall
      sensitivities for detecting > or = 50% and > or = 70% stenoses were 75.0% and
      84.3%, respectively, for Tl-201, and 71.9% and 80.4%, respectively, for Tc-99m
      sestamibi perfusion studies (p = 0.48). The specificity for lesions > or = 50%
      was 61.9% for Tl-201 and 85.7% for Tc-99m sestamibi perfusion (p = 0.07), whereas
      for lesions > or = 70% it was 58.8% for Tl-201 and 82.4% for Tc-99m sestamibi
      perfusion (p = 0.01). When the 34 patients with a normal coronary angiogram were
      added to the group of 30 normal volunteers, the "specificity" for lesions > or =
      70% was 67.2% for Tl-201, 84.4% for Tc-99m sestamibi SPECT perfusion (p = 0.02)
      and 92.2% for Tc-99m sestamibi gated SPECT (p = 0.0004). CONCLUSIONS: Both Tl-201
      SPECT and Tc-99m sestamibi SPECT perfusion studies had a similar sensitivity for
      the detection of CAD in women. However, Tc-99m sestamibi SPECT perfusion imaging
      shows a significantly better specificity, which is further enhanced by the use of
      ECG gating.

PMID- 8996298
TI  - A detailed angiographic analysis of patients with ambulatory electrocardiographic
      ischemia: results from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study
      angiographic core laboratory.
AB  - OBJECTIVES: The purpose of this Asymptomatic Cardiac Ischemia Pilot (ACIP) data
      bank study was to characterize angiographic features of coronary pathology of
      patients enrolled in the ACIP study. BACKGROUND: Ischemia during ambulatory
      electrocardiographic (AECG) monitoring is associated with increased morbidity and
      mortality. Reports relating AECG ischemia to severity or complexity of coronary
      artery disease are few in number and small in size and have produced conflicting
      results. METHODS: Coronary angiograms from patients with asymptomatic AECG
      ischemia enrolled in the ACIP study were reviewed at a central core laboratory.
      Quantitative measurement of percent stenosis and Thrombolysis in Myocardial
      Infarction flow grades were used to assess the severity of coronary artery
      disease. Lesions were also evaluated for the presence of intracoronary thrombus,
      ulceration and lumen contour as indicators of stenosis complexity. In addition,
      comparisons were made with 27 patients screened for the ACIP study, but who were
      found ineligible because they did not have AECG ischemia on 48-h Holter
      monitoring. RESULTS: A total of 329 (75%) of 439 patients with AECG ischemia had
      multivessel coronary artery disease. Proximal stenoses > or = 50% diameter
      reduction were common in patients with AECG ischemia (62.2%), as were proximal
      stenoses > or = 70% (38.7%). Features suggesting complex plaque were found in
      50.1% of patients with AECG ischemia. CONCLUSIONS: Multivessel coronary artery
      disease, severe proximal stenoses and features of complex plaque were observed
      frequently in patients who exhibited AECG ischemia. The presence of severe and
      complex coronary artery disease may explain, in part, the increased risk for
      adverse outcome associated with ischemia during activities of daily life.

PMID- 8996299
TI  - Importance of nitric oxide in the coronary artery at rest and during pacing in
      humans.
AB  - OBJECTIVES: The purpose of this study was to investigate the role of endothelium
      dependent vascular regulation in the human coronary circulation during rest and
      hyperemic states. BACKGROUND: Evidence of the role of nitric oxide (NO) during
      metabolic demand is not consistent in animal and human coronary circulation.
      METHODS: NG-Monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis,
      was infused into the left anterior descending coronary artery at rest and during
      rapid atrial pacing in 18 subjects--9 with normal coronary arteries (control) and
      9 with atherosclerotic coronary arteries. The diameter of the epicardial coronary
      artery was measured by quantitative coronary angiography. Vasodilation of the
      coronary microcirculation was assessed using an intracoronary Doppler FloWire.
      RESULTS: Infusion of 25 mumol/min of L-NMMA reduced the diameter of the proximal
      and distal epicardial coronary artery segments by 8 +/- 2% (mean +/- SE) and 11
      +/- 2%, respectively (p < 0.05) in the control subjects. The coronary blood flow
      (CBF) decreased by 33 +/- 13% during L-NMMA infusion. L-NMMA caused similar
      changes in the diameter of the distal epicardial segment and the CBF in patients
      with coronary artery disease. The proximal vessel diameter did not change
      significantly during infusion of L-NMMA. During pacing, infusion of L-NMMA caused
      the same changes in vessel diameter as before pacing in both groups, but did not
      affect CBF. CONCLUSIONS: Our findings indicate that NO synthesis maintains basal
      vasomotor tone in both conduit and resistance vessels in the normal human
      coronary circulation. Although NO release was impaired in the large epicardial
      coronary arteries in patients with atherosclerosis, NO still regulated vascular
      tone in the small epicardial coronary arteries and arterioles. Our results
      suggest that vasodilation in arterioles during increased myocardial oxygen demand
      is mediated by metabolic or myogenic mechanisms, or both, rather than by
      endothelium-dependent production of NO.

PMID- 8996300
TI  - Age-gender influence on the rate-corrected QT interval and the QT-heart rate
      relation in families with genotypically characterized long QT syndrome.
AB  - OBJECTIVES: We sought to analyze age-gender differences in the rate-corrected QT
      (QTc) interval in the presence of a QT-prolonging gene. BACKGROUND: Compared with
      men, women exhibit a longer QTc interval and an increased propensity toward
      torsade de pointes. In normal subjects, the QTc gender difference reflects QTc
      interval shortening in men during adolescence. METHODS: QTc intervals were
      analyzed according to age (< 16 or > or = 16 years) and gender in 460 genotyped
      blood relatives from families with long QT syndrome linked to chromosome 11p
      (KVLQT1; n = 199), 7q (HERG; n = 208) or 3p (SCN5A; n = 53). RESULTS: The mean
      QTc interval in genotype-negative blood relatives (n = 240) was shortest in men,
      but similar among women, boys and girls. For genotype-positive blood relatives,
      men exhibited the shortest mean QTc interval in chromosome 7q- and 11p-linked
      blood relatives (n = 194), but not in the smaller 3p-linked group (n = 26). Among
      pooled 7q- and 11p-linked blood relatives, multiple regression analysis
      identified both genotype (p < 0.001) and age-gender group (men vs.
      women/children; p < 0.001) as significant predictors of the QTc interval; and
      heart rate (p < 0.001), genotype (p < 0.001) and age-gender group (p = 0.01) as
      significant predictors of the absolute QT interval. A shorter mean QT interval in
      men was most evident for heart rates < 60 beats/min. CONCLUSIONS: In familial
      long QT syndrome linked to either chromosome 7q or 11p, men exhibit shorter mean
      QTc values than both women and children, for both genotype-positive and -negative
      blood relatives. Thus, adult gender differences in propensity toward torsade de
      pointes may reflect the relatively greater presence in men of a factor that
      blunts QT prolongation responses, especially at slow heart rates.

PMID- 8996301
TI  - Electrophysiologic mechanisms of antiarrhythmic efficacy of a sotalol and class
      Ia drug combination: elimination of reverse use dependence.
AB  - OBJECTIVES: We sought to determine the electrophysiologic mechanisms explaining
      the efficacy of combination therapy with DL-sotalol and a type Ia drug in the
      treatment of ventricular tachycardia (VT). BACKGROUND: Combination antiarrhythmic
      drug therapy with low dose DL-sotalol plus a type Ia antiarrhythmic agent has
      been shown to prevent spontaneous and induced VT. The mechanisms underlying the
      efficacy of this drug combination have not been fully elucidated. METHODS: We
      studied 32 patients with spontaneous sustained VT by using programmed electrical
      stimulation in the drug-free condition and after treatment with DL-sotalol
      (average dose [mean +/- SE] 151 +/- 8 mg/day) and a class Ia agent (quinidine,
      1,337 +/- 59 mg/day, or procainamide, 2,083 +/- 327 mg/day). Sustained VT was
      induced in all patients at baseline study, and induction was reattempted during
      drug therapy. Monophasic action potential duration at 90% repolarization (APD90)
      and ventricular effective refractory period (ERP) were recorded with use of a
      contact electrode. RESULTS: Ventricular ERP increased from 258 +/- 4 ms at
      baseline to 310 +/- 6 ms at a 600-ms drive cycle length (DCL600) with treatment
      (p < 0.001). APD90 increased from 288 +/- 6 ms by +10.1% at DCL600 and from 267
      +/- 7 ms by +13.3% at a 400-ms drive cycle length (DCL400) (p < 0.001). Paced QRS
      duration increased from 141 +/- 3 to 158 +/- 6 ms at DCL400 (p < 0.05). At
      baseline, the shortest achieved coupling interval between successive propagated
      extrastimuli decreased progressively with respect to the first extrastimulus,
      following double and triple extrastimuli, at both DCL600 (-14.0% and -20.0%,
      respectively) and at DCL400 (-16.4% and -22.4%, respectively). This "peeling
      back" of refractoriness was attenuated on therapy with sotalol plus a class Ia
      antiarrhythmic agent to -6.7% and -10.5% (DCL600, p < 0.05), and -8.1%, -9.5%
      (DCL400, p < 0.05), for double and triple extrastimuli, respectively. The
      absolute prolongation of functional refractory periods by the drug combination
      increased with successive extrastimuli, from 55 +/- 6 ms for the V1V2 interval to
      75 +/- 6 ms for V2V3 and 67 +/- 6 ms for V3V4 at DCL600, and from 51 +/- 5 ms for
      V1V2 to 69 +/- 6 ms for V2V3 and 74 +/- 7 ms for V3V4 at DCL400 (p < 0.001).
      CONCLUSIONS: The combination of low dose sotalol and a class Ia agent greatly
      prolongs refractoriness. The magnitude of the effect increases at shorter
      coupling intervals.

PMID- 8996302
TI  - Atrial fibrillation activates platelets and coagulation in a time-dependent
      manner: a study in patients with paroxysmal atrial fibrillation.
AB  - OBJECTIVES: To determine whether atrial fibrillation (AF) alone affects the
      fibrinocoagulation system, we examined the relation between fibrinocoagulation
      activity and duration of AF in patients with paroxysmal AF (PAF). BACKGROUND:
      Patients with chronic AF are at higher risk for stroke and a hypercoagulative
      state. It is not clear whether this hypercoagulative state is attributable to AF
      alone or to the underlying disease. There are no reports on the
      fibrinocoagulation properties in PAF. METHODS: Fibrinocoagulation variables in 21
      patients with PAF were measured during AF and 7 days after recovery of sinus
      rhythm. There were positive correlations between the duration of AF and beta
      thromboglobulin, platelet factor 4, thrombin-antithrombin III complex and
      fibrinogen. These variables increased significantly 12 h after the occurrence of
      PAF; thus, patients were classified into two groups according to the duration of
      PAF: PAF-I group (< 12 h, n = 10), PAF-II group (> or = 12 h, n = 11). Nine age
      matched, healthy subjects formed the control group. RESULTS: Levels of beta
      thromboglobulin and platelet factor 4 were significantly higher (p < 0.001) by
      two-way repeated measures analysis of variance (ANOVA), and thrombin-antithrombin
      III complex and fibrinogen levels tended to be but were not significantly higher
      (p = 0.06, ANOVA), in the PAF-II group than in the PAF-I group. There were no
      significant differences between groups in activated partial thromboplastin time,
      D-dimer or plasmin inhibitor complex. CONCLUSIONS: These results indicate that AF
      itself enhances platelet aggregation and coagulation, which are influenced by the
      duration of AF. The acceleration of platelet activity and coagulability occurred
      12 h after the occurrence of AF.

PMID- 8996303
TI  - Long-term follow-up after radiofrequency modification of the atrioventricular
      node in patients with atrial fibrillation.
AB  - OBJECTIVES: The purpose of this study was to describe the long-term follow-up
      results in 62 patients with atrial fibrillation and an uncontrolled ventricular
      rate, who underwent radiofrequency modification of the atrioventricular (AV)
      node. BACKGROUND: Previous studies in small numbers of patients have suggested
      that radiofrequency modification may be effective in controlling the ventricular
      rate in patients with atrial fibrillation, but long-term follow-up data have been
      lacking. METHODS: The subjects of this study were 62 consecutive patients (mean
      age +/- SD 65 +/- 14 years; 43 with structural heart disease) who underwent an
      attempt at radiofrequency modification of the AV node because of symptomatic,
      drug-refractory atrial fibrillation with an uncontrolled ventricular rate. The
      atrial fibrillation was chronic in 46 patients and paroxysmal in 16.
      Radiofrequency energy was applied to the posteroseptal or mid-septal right atrium
      to lower the ventricular rate in atrial fibrillation to 120 to 130 beats/min
      during an infusion of 4 micrograms/min of isoproterenol. RESULTS: Short-term
      control of the ventricular rate was successfully achieved without the induction
      of pathologic AV block in 50 (81%) of 62 patients. Inadvertent high degree AV
      block occurred in 10 (16%) of 62 patients, with the AV block occurring at the
      time of the procedure in 6 patients and 36 to 72 h after the procedure in 4.
      During 19 +/- 8 months of follow-up (range 4 to 33), 5 (10%) of 50 patients had a
      symptomatic recurrence of an uncontrolled rate during atrial fibrillation.
      Overall, adequate rate control at rest and during exertion, without pathologic AV
      block, was achieved long term in 45 (73%) of 62 patients. Among 37 patients with
      a successful outcome, left ventricular ejection fraction increased from (mean +/-
      SD) 0.44 +/- 0.14 to 0.51 +/- 0.10 one year later (p < 0.001). Complications
      other than AV block included polymorphic ventricular tachycardia 10 to 24 h after
      the procedure in two patients who had a predisposing factor for ventricular
      tachycardia and sudden death 1 to 5 months after the procedure in two patients
      with idiopathic dilated cardiomyopathy, one of whom had a pacemaker for AV block.
      CONCLUSIONS: In approximately 70% of properly selected patients with atrial
      fibrillation and an uncontrolled ventricular rate, radiofrequency modification of
      the AV node results in excellent long-term control of the ventricular rate at
      rest and during exertion.

PMID- 8996304
TI  - Cost-effectiveness of transesophageal echocardiographic-guided cardioversion: a
      decision analytic model for patients admitted to the hospital with atrial
      fibrillation.
AB  - OBJECTIVES: Using a decision-analytic model, we sought to examine the cost
      effectiveness of three strategies for cardioversion of patients admitted to the
      hospital with atrial fibrillation. BACKGROUND: Transesophageal echocardiographic
      (TEE)-guided cardioversion has been proposed as a method for early cardioversion
      of patients with atrial fibrillation. The cost-effectiveness of this approach,
      relative to conventional therapy, has not been studied. METHODS: We ascertained
      the cost per quality-adjusted life-year (QALY) of three strategies: 1)
      conventional therapy--transthoracic echocardiography (TTE) and warfarin therapy
      for 1 month before cardioversion; 2) initial TTE, followed by TEE and early
      cardioversion if no thrombus is detected; 3) initial TEE, with early
      cardioversion if no thrombus is detected. With strategies 2 and 3, if a thrombus
      is seen, follow-up TEE is performed. If no thrombus is seen, cardioversion is
      then performed. All strategies utilized anticoagulation before and extending for
      1 month after cardioversion. Life expectancy, utilities (quality-of-life weights)
      and event probabilities were ascertained from published reports. Cost estimates
      were based on published data and hospital accounting information. RESULTS:
      Transesophageal echocardiographic-guided early cardioversion (strategy 3: cost
      $2,774, QALY 8.49) dominates TTE/TEE-guided cardioversion (strategy 2: cost
      $3,106, QALY 8.48) and conventional therapy (strategy 1: cost $3,070, QALY 8.48)
      because it is the least costly with similar effectiveness. Sensitivity analyses
      demonstrated that TEE-guided cardioversion (strategy 3) dominates conventional
      therapy if the risk of stroke after TEE negative for atrial thrombus is slightly
      less than that after conventional therapy (baseline estimate 0.8%). The results
      also depend on the risk of major hemorrhage but are less sensitive to baseline
      estimates of morbidity from TEE, cost of TTE, cost of hospital admission for
      cardioversion and utilities for health states. CONCLUSIONS: On the basis of a
      decision-analytic model, TEE-guided early cardioversion, without TTE, is a
      reasonable cost-saving alternative to conventional therapy for patients admitted
      to the hospital with atrial fibrillation. Such a strategy appears particularly
      beneficial for patients with an increased risk of hemorrhagic complications.
      Future clinical studies examining the TEE strategy should consider eliminating
      initial TTE and carefully assess both the thromboembolic and hemorrhagic risk.

PMID- 8996305
TI  - Left atrial chamber and appendage function after internal atrial defibrillation:
      a prospective and serial transesophageal echocardiographic study.
AB  - OBJECTIVES: The purpose of this prospective study was to assess left atrial
      chamber and appendage function after internal atrial defibrillation of atrial
      fibrillation and to evaluate the time course of recovery. BACKGROUND: External
      cardioversion of atrial fibrillation may result in left atrial appendage
      dysfunction ("stunning") and may promote thrombus formation. In contrast to
      external cardioversion, internal atrial defibrillation utilizes lower energies;
      however, it is unknown whether the use of lower energies may avoid stunning of
      the left atrial appendage. METHODS: Transesophageal and transthoracic
      echocardiography were performed in 20 patients 24 h before and 1 and 7 days after
      internal atrial defibrillation to assess both left atrial chamber and appendage
      function. Transthoracic echocardiography was again performed 28 days after
      internal atrial defibrillation to assess left atrial function. The incidence and
      degree of spontaneous echo contrast accumulation (range 1+ to 4+) was noted, and
      peak emptying velocities of the left atrial appendage were measured before and
      after internal atrial defibrillation. To determine left atrial mechanical
      function, peak A wave velocities were obtained from transmitral flow velocity
      profiles. RESULTS: Sinus rhythm was restored in all patients. The mean +/- SD
      peak A wave velocities increased gradually after cardioversion, from 0.47 +/-
      0.16 m/s at 24 h to 0.61 +/- 0.13 m/s after 7 days (p < 0.05) and 0.63 +/- 0.13
      m/s after 4 weeks. Peak emptying velocities of the left atrial appendage were
      0.37 +/- 0.16 m/s before internal atrial defibrillation, decreased significantly
      after internal atrial defibrillation to 0.23 +/- 0.1 m/s at 24 h (p < 0.01) and
      then recovered to 0.49 +/- 0.23 m/s (p < 0.01) after 7 days. The corresponding
      values for the degree of spontaneous echo contrast were 1.2 +/- 1.2 before
      internal atrial defibrillation versus 2.0 +/- 1.0 (p < 0.01) and 1.1 +/- 1.3 (p <
      0.01) 1 and 7 days after cardioversion, respectively. One patient developed a new
      thrombus in the left atrial appendage, and another had a thromboembolic event
      after internal atrial defibrillation. CONCLUSIONS: Internal atrial defibrillation
      causes depressed left atrial chamber and appendage function and may result in the
      subacute accumulation of spontaneous echo contrast and development of new thrombi
      after cardioversion. These findings have important clinical implications for
      anticoagulation therapy before and after low energy internal atrial
      defibrillation in patients with atrial fibrillation.

PMID- 8996306
TI  - Variations in cholesterol management practices of U.S. physicians.
AB  - OBJECTIVES: This study sought to evaluate national cholesterol management
      practices of U.S. physicians. BACKGROUND: Past studies show that nonclinical
      factors affect physician practices. We tested the hypothesis that physician and
      patient characteristics influence cholesterol management. METHODS: We used a
      stratified, random sample of 2,332 office-based physicians providing 56,215
      visits to adults in the 1991-1992 National Ambulatory Medical Care Surveys. We
      investigated physicians' reporting of cholesterol-related screening, counseling
      or medications during office visits and used multiple logistic regression to
      assess independent predictors. RESULTS: An estimated 1.12 billion adult office
      visits occurred in 1991 and 1992 (95% confidence interval 1.06 to 1.18 billion).
      For the 1.03 billion visits by patients without reported hyperlipidemia,
      cholesterol screening (2.8% of visits) and counseling (1.2%) were not frequent.
      The likelihood of screening increased with older age, cardiovascular disease risk
      factors, white race and private insurance. We estimate that only 1 in 12 adults
      received cholesterol screening annually. In the 85 million visits by patients
      with hyperlipidemia, cholesterol testing was reported in 22.9%, cholesterol
      counseling in 34.4% and lipid-lowering medications in 23.1%. Testing was more
      likely in diabetic and nonobese patients. Counseling was more likely with younger
      age, cardiovascular disease and private insurance. Medications use was associated
      with cardiovascular disease, Northeast region of the United States, nonobese
      patients and visits to internists. Physician practices did not differ by patient
      gender. CONCLUSIONS: Although clinical conditions strongly influence cholesterol
      management, the appropriateness of variations noted by payment source, geographic
      region and physician specialty deserve further evaluation. These variations and
      the low estimated volume of services suggest that physicians have not fully
      adopted recommended cholesterol management practices.

PMID- 8996307
TI  - Effects of dihydrocodeine on chemosensitivity and exercise tolerance in patients
      with chronic heart failure.
AB  - OBJECTIVES: We sought to test the hypothesis that suppression of chemosensitivity
      (respiratory response to arterial blood gases) with dihydrocodeine may improve
      dyspnea and exercise tolerance in patients with chronic heart failure.
      BACKGROUND: Exertional dyspnea is a common limiting symptom in patients with
      chronic heart failure. The mechanisms underlying this symptom are not fully
      understood but may be related to increased ventilation caused, in part, by the
      augmentation of chemosensitivity. Suppression of chemosensitivity with mild
      opiates may thus improve this symptom as well as exercise tolerance. METHODS:
      Twelve men with chronic heart failure (mean [+/-SE] age 65.5 +/- 1.5 years, range
      58 to 75; left ventricular ejection fraction 21.3 +/- 3.0%, range 8 to 39)
      received placebo or dihydrocodeine (1 mg/kg body weight) on two separate days in
      a randomized, double-blind design. One hour later, hypoxic and hypercapnic
      chemosensitivities were assessed using the transient inhalations of pure nitrogen
      and the rebreathing of 7% carbon dioxide in 93% oxygen, followed by treadmill
      cardiopulmonary exercise testing. The symptoms of dyspnea and fatigue during the
      exercise test were assessed using a modified Borg scale from 0 to 10. RESULTS:
      There was a significant fall in hypoxic and hypercapnic chemosensitivities with
      dihydrocodeine administration compared with placebo (0.447 +/- 0.096 vs. 0.746 +/
      0.104 liter/min per percent arterial oxygen saturation, p = 0.005; 2,480 +/-
      0.234 vs. 2.966 +/- 0.283 liter/min per mm Hg, p = 0.01, respectively). Exercise
      duration was prolonged from 455 +/- 27 s on placebo to 512 +/- 27 s (p = 0.001)
      with dihydrocodeine, and peak oxygen consumption increased from 18.0 +/- 0.6 to
      19.7 +/- 0.6 ml/kg per min (p = 0.002). The ventilatory response to exercise,
      characterized by the regression slope relating minute ventilation to carbon
      dioxide output, decreased from 34.19 +/- 2.35 to 30.85 +/- 1.91 (p = 0.01). With
      dihydrocodeine administration, the change in the modified Borg score for dyspnea
      was -0.80 (p = 0.003) at 6 min and -0.33 (p = 0.52) at peak exercise, whereas
      that for fatigue did not change significantly. Arterial oxygen saturation was
      maintained during exercise despite dihydrocodeine administration (99.3% at rest
      vs. 98.9% at peak exercise, p = 0.21). CONCLUSIONS: Augmented chemosensitivity is
      important in the pathophysiology of chronic heart failure. Its suppression with
      dihydrocodeine was associated with a reduction of exercise ventilation, an
      improvement in exercise tolerance and a decrease in breathlessness. Pharmacologic
      modulation of chemosensitivity may benefit patients with chronic heart failure
      and merits further investigation.

PMID- 8996308
TI  - Determinants of pulmonary hypertension in left ventricular dysfunction.
AB  - OBJECTIVES: This study sought to analyze the determinants of pulmonary
      hypertension in patients with left ventricular dysfunction. BACKGROUND: Pulmonary
      hypertension in patients with left ventricular dysfunction is a predictor of poor
      outcome. The independent role of cardiac functional abnormalities in the genesis
      of pulmonary hypertension is unclear. METHODS: In 102 consecutive patients with
      primary left ventricular dysfunction (ejection fraction < 50%), systolic
      pulmonary artery pressure was prospectively measured by Doppler echocardiography
      (using tricuspid regurgitant velocity), and left ventricular systolic and
      diastolic function, functional mitral regurgitation, cardiac output and left
      atrial volume were quantified. RESULTS: Systolic pulmonary artery pressure was
      elevated in patients with left ventricular dysfunction (51 +/- 14 mm Hg [mean +/-
      SD]), but the range was wide (23 to 87 mm Hg). Of the numerous variables
      correlating significantly with systolic pulmonary artery pressure, the strongest
      were mitral deceleration time (r = -0.61, p = 0.0001; odds ratio of pulmonary
      pressure > or = 50 mm Hg [95% confidence interval] if < 150 ms, 48.8 [14.8 to
      161]) and mitral effective regurgitant orifice (r = 0.50, p = 0.0001; odds ratio
      [95% confidence interval] if > or = 20 mm2, 5.9 [2.3 to 15.5]). In multivariate
      analysis, these two variables were the strongest predictors of systolic pulmonary
      artery pressure in association with age (p = 0.005). Ejection fraction or end
      systolic volume was not an independent predictor of pulmonary artery pressure.
      CONCLUSIONS: Pulmonary hypertension is frequent and highly variable in patients
      with left ventricular dysfunction. It is not independently related to the degree
      of left ventricular systolic dysfunction but is strongly associated with
      diastolic dysfunction (shorter mitral deceleration time) and the degree of
      functional mitral regurgitation (larger effective regurgitant orifice). These
      results emphasize the importance of assessing diastolic function and quantifying
      mitral regurgitation in patients with left ventricular dysfunction.

PMID- 8996309
TI  - Spectrum of alcohol-induced myocardial damage detected by indium-111-labeled
      monoclonal antimyosin antibodies.
AB  - OBJECTIVES: We sought to determine the prevalence, intensity and evolving changes
      of myocardial damage detected by myocardial uptake of antimyosin antibodies in
      patients with alcohol-induced dilated cardiomyopathy, alcohol addicts attending a
      detoxification unit and healthy subjects with short-term alcohol consumption.
      BACKGROUND: Evidence of alcohol-induced myocardial damage may be provided by
      myocardial uptake of indium-111-labeled monoclonal antimyosin antibodies. The
      spectrum of such damage in patients who are heavy drinkers (> 100 g for > 10
      years), with or without cardiomyopathy, and the impact of short-term alcohol
      ingestion on antimyosin antibody uptake have not been adequately explored.
      METHODS: One hundred twenty antimyosin studies were performed in 56 patients with
      dilated cardiomyopathy (group I), 15 alcohol addicts attending a detoxification
      unit (group II) and 6 volunteers for short-term alcohol ingestion (group III).
      Estimation of antibody uptake was calculated through a heart/lung ratio (HLR)
      (normal < 1.55). RESULTS: The 56 patients in group I (54 men, 2 women; mean [+/
      SD] age 46 +/- 11 years) had consumed 123 +/- 60 g/day of alcohol for 21 +/- 9
      years, for a cumulative intake of 914 +/- 478 kg. Mean duration of symptoms was
      46 +/- 49 months. Mean left ventricular end-diastolic diameter was 71 +/- 10 mm,
      and mean ejection fraction was 28 +/- 12%. No differences in New York Heart
      Association functional class, ventricular size or ejection fraction were noted
      between 28 active and 28 past consumers, except for the prevalence and intensity
      of antibody uptake (75% vs. 32%, p < 0.001) and HLR (1.75 +/- 0.26 vs. 1.49 +/-
      0.17, p = 0.0001). In 19 patients in the active group restudied after alcohol
      withdrawal, antibody uptake decreased (from 1.76 +/- 0.17 to 1.55 +/- 0.19, p <
      0.001), and ejection fraction improved (from 30 +/- 12% to 43 +/- 16%, (p <
      0.001). No changes occurred in the 15 past consumers restudied. The 15 male
      patients in group II (mean age 36 +/- 4 years) had consumed 156 +/- 59 g/day for
      17 +/- 5 years, for a cumulative alcohol intake of 978 +/- 537 kg, an amount
      similar to that in patients in group I, but antimyosin antibody uptake was
      detected in only 3 (20%) of 15 patients. None of six group III subjects developed
      antibody uptake after short-term ethanol ingestion. Despite the small sample
      size, the power to detect clinically relevant differences in most variables that
      did not reach statistical significance was amply sufficient. CONCLUSIONS: In
      alcohol-induced dilated cardiomyopathy, alcohol withdrawal is associated with the
      reduction or disappearance of myocardial damage and improvement of function. The
      difference in prevalence of antimyosin antibody uptake in patients with and
      without cardiac disease who consume similar amounts of alcohol suggests the
      presence of those with different myocardial susceptibilities to alcohol. Short
      term ethanol ingestion in healthy subjects does not induce detectable uptake of
      antimyosin antibodies.

PMID- 8996310
TI  - Iodine-123 metaiodobenzylguanidine scintigraphic assessment of myocardial
      sympathetic innervation in patients with familial amyloid polyneuropathy.
AB  - OBJECTIVES: This study attempted to assess myocardial sympathetic innervation
      using iodine-123 (I-123) metaidobenzylguanidine (MIBG) imaging in patients with
      familial amyloid polyneuropathy. BACKGROUND: Signs and symptoms of cardiac
      autonomic dysfunction are commonly seen in patients with cardiac amyloidosis.
      However, the incidence and magnitude of abnormalities in myocardial sympathetic
      nerve function by means of I-123 MIBG imaging and their relation to clinical
      findings, cardiac function and the results of thallium-201 (Tl-201) and
      technetium-99m pyrophosphate (Tc-99m PYP) myocardial scanning have not yet been
      clarified. METHODS: We performed M-mode, two-dimensional and Doppler
      echocardiography and I-123 MIBG, Tl-201 and Tc-99m PYP imaging of the heart in 12
      patients with familial amyloid polyneuropathy and biopsy-proved cardiac
      amyloidosis. RESULTS: Ten of 12 patients had no clinical evidence of overt heart
      disease, but left ventricular (LV) wall thickening was observed in 4 of these 10.
      Left ventricular percent fractional shortening and Doppler transmitral flow
      velocity patterns were found to be normal in all 12 patients. Eight of 12
      patients showed no myocardial MIBG accumulation, with limited uptake in the
      remaining 4 demonstrated only in the LV anterior wall. Diffuse but mild
      myocardial uptake of Tc-99m PYP occurred in only 4 of 12 patients, and all 12 had
      normal results on Tl-201 myocardial scanning. Complete defects on myocardial MIBG
      scans were found in five of eight patients with negative findings on Tc-99m PYP
      myocardial scanning. The incidence and magnitude of myocardial uptake of MIBG
      were independent of clinical findings, extent of endomyocardial amyloid
      deposition, electrocardiographic QRS voltage and ventricular wall thickness.
      CONCLUSIONS: Patients with familial amyloid polyneuropathy show a high incidence
      of myocardial adrenergic denervation with viable myocardium that can be
      identified very early in cardiac amyloidosis, before the development of
      clinically apparent heart disease, ventricular wall thickening, significant LV
      systolic and diastolic dysfunction and positive findings on Tc-99m PYP myocardial
      scanning.

PMID- 8996311
TI  - Echocardiographic assessment of commissural calcium: a simple predictor of
      outcome after percutaneous mitral balloon valvotomy.
AB  - OBJECTIVES: This study was undertaken to determine whether the presence of
      calcium in the mitral valve commissures, as demonstrated echocardiographically,
      could predict outcome and to compare this with an established echocardiographic
      scoring system. BACKGROUND: Percutaneous mitral balloon valvotomy is an effective
      form of treatment for mitral valve stenosis. It is important to identify patients
      who would benefit from this procedure. Commissural splitting is the dominant
      mechanism by which mitral valve stenosis is relieved by this technique, and thus
      commissural morphology may predict outcome. METHODS: One hundred forty-nine
      consecutive patients who underwent percutaneous mitral balloon valvotomy at the
      Mayo Clinic were evaluated retrospectively. The morphology of the mitral valve
      apparatus on the baseline echocardiograms was scored in blinded manner using a
      semiquantitative grading system of leaflet thickening, mobility, calcification
      and subvalvular thickening (Abascal score). Additionally, each of the medial and
      lateral commissures was graded for the presence or absence of calcification. End
      points were death, New York Heart Association functional class, repeat
      percutaneous mitral balloon valvotomy and mitral valve replacement at follow-up.
      RESULTS: The mean follow-up period was 1.8 years (maximum 7.9 years). Univariate
      predictors of death and all events combined included age, the use of a double
      balloon technique, the presence of calcium in a commissure and the Abascal score,
      as continuous variables. Patients with an Abascal score < or = 8 showed a trend
      toward improved survival at 36 months free of death, repeat percutaneous mitral
      balloon valvotomy or mitral valve replacement (78 +/- 6% vs. 67 +/- 8%, p = 0.07)
      and free of all events combined (75 +/- 6% vs. 64 +/- 8%, p = 0.07) versus those
      patients with a score > 8. However, survival at 36 months free of death, repeat
      percutaneous mitral balloon valvotomy or mitral valve replacement (86 +/- 4% vs.
      40 +/- 4%) and free of all events combined (82 +/- 5% vs. 38 +/- 10%) at follow
      up was significantly different between patients without commissural calcium and
      those with commissural calcium (p < 0.001). In a Cox regression model with
      Abascal score and commissural calcium and their interaction, calcification
      emerged as the only significant variable (p < 0.01). CONCLUSIONS: The presence of
      commissural calcium is a strong predictor of outcome after percutaneous mitral
      balloon valvotomy. Patients with evidence of calcium in a commissure have a lower
      survival rate and a higher incidence of mitral valve replacement and all end
      points combined. Thus, the simple presence or absence of commissural
      calcification assessed by two-dimensional echocardiography can be used to predict
      outcome.

PMID- 8996312
TI  - Age dependency of left ventricular diastolic function in pressure overload
      hypertrophy.
AB  - OBJECTIVES: We sought to evaluate whether age is a determinant of left
      ventricular (LV) pressure overload hypertrophy and whether diastolic function
      influenced the aging process. BACKGROUND: The adaptation of the left ventricle to
      chronic pressure overload is a complex process of hormonal, structural and
      hemodynamic factors. Different responses in the elderly patients have been
      described. METHODS: LV biplane cineangiography, micromanometry and endomyocardial
      biopsies were carried out in 57 patients with pure or predominant aortic
      stenosis. Patients were classified into a senior (< 60 years, mean age +/- SD 46
      +/- 10 years, n = 35) and an elderly (< 65 years; mean age 70 +/- 4 years, n =
      22) study group. LV systolic function was evaluated from biplane ejection
      fraction and midwall fractional shortening, whereas diastolic function was
      assessed from the time constant of LV pressure decay, peak filling rate and the
      constant of myocardial stiffness. Biopsy samples were examined morphometrically
      for interstitial fibrosis, fibrous content, muscle fiber diameter and volume
      fraction of myofibrils. RESULTS: Gender distribution and the severity of aortic
      stenosis were comparable in the two patient groups. LV peak systolic and end
      diastolic pressures were significantly higher in the elderly than in the senior
      group. LV ejection fraction and midwall fractional shortening were comparable in
      the two groups. The time constant of relaxation and the myocardial stiffness
      constant were greater in the elderly than in the senior group whereas the early
      peak filling rate was significantly reduced in the elderly group. Interstitial
      fibrosis was increased, although not significantly (p < 0.06), and fibrous
      content was enhanced (p < 0.001) in elderly patients with respect to the senior
      group. There was a linear correlation between age and myocardial stiffness (r =
      0.55), p < 0.0001) and an inverse relation between age and early peak filling
      rate (r = 0.52, p < 0.0001). CONCLUSIONS: In the presence of a comparable degree
      of aortic valve stenosis, elderly patients (> 65 years) present with more severe
      LV hypertrophy than do senior patients (< 60 years). Therefore elderly patients
      have a more pronounced impairment of LV diastolic function, whereas systolic
      function is preserved. Thus, there is an age dependency of LV pressure overload
      hypertrophy that can be explained by the longer duration of pressure overload or
      an exhaustion of the adaptation process in the elderly.

PMID- 8996313
TI  - Age-dependent changes in cardiac muscarinic receptor function in healthy
      volunteers.
AB  - OBJECTIVES: This study was conducted to determine possible age-dependent changes
      in the responsiveness of human cardiac muscarinic receptors. BACKGROUND: It is
      well known that the baroreflex activity decreases with aging. However, the
      mechanisms underlying this phenomenon are not completely understood at present.
      METHODS: In six healthy young (mean [+/-SEM] age 26 +/- 2 years) and six healthy
      older volunteers (mean age 60 +/- 2 years), we determined 1) the effects of
      graded doses of atropine (bolus application, six doses, each for 20 min, range
      0.03 to 0.96 mg) and the M1-cholinoceptor selective antagonist pirenzepine (bolus
      application, eight doses, each for 20 min, range 0.04 to 10 mg) on heart rate,
      blood pressure and systolic time intervals (as measure of inotropism); and 2) the
      baroreflex activity by assessing the bradycardic response to phenylephrine.
      RESULTS: Atropine and pirenzepine caused biphasic effects on heart rate: At lower
      doses (< 0.12 mg for atropine, < 5 mg for pirenzepine) they decreased heart rate,
      whereas at higher doses they increased heart rate. Heart rate decreases induced
      by both antimuscarinic drugs were significantly larger in the young volunteers
      than in the older volunteers, whereas heart rate increases were not significantly
      different for both drugs. Atropine and pirenzepine did not significantly affect
      blood pressure and systolic time intervals. Infusion of graded doses of
      phenylephrine (four doses ranging from 0.1 to 1.0 microgram/kg body weight per
      min for 15 min each) caused a higher increase in systolic blood pressure and a
      smaller decrease in heart rate at each dose in the older volunteers than in the
      young volunteers. The slopes of the regression lines were 16 +/- 2.3 ms/mm Hg for
      the young and 6 +/- 0.5 ms/mm Hg for the older volunteers (p < 0.01).
      CONCLUSIONS: Human cardiac muscarinic receptor activity is diminished with
      increasing age; such decreased cardiac muscarinic receptor activity could
      contribute to the decrease in baroreflex activity with aging. In contrast,
      antimuscarinic drugs seem to have no effect on human cardiac contractility.

PMID- 8996314
TI  - Arrhythmia and mortality after the Mustard procedure: a 30-year single-center
      experience.
AB  - OBJECTIVES: Our purpose was to assess the risk factors for late mortality, loss
      of sinus rhythm and atrial flutter after the Mustard operation. BACKGROUND: The
      Mustard operation provides correction of cyanosis with low surgical risk in
      transposition of the great vessels. However, right ventricular failure, loss of
      sinus rhythm, atrial flutter and death are frequent long-term complications.
      METHODS: Records of 534 children who underwent the Mustard operation at a single
      center since 1962 were reviewed for demographic, anatomic, electrocardiographic
      and physiologic predictors and outcomes. RESULTS: There were 52 early deaths
      (9.7%). Survival analysis was undertaken for 478 early survivors with a mean
      follow-up interval of 11.6 +/- 7.2 years. There were 77 late deaths (16.1%), with
      sudden death (n = 31) the most frequent cause. Survival estimates were 89% at 5
      years and 76% at 20 years of age. Risk factors were an earlier date of operation,
      operative period arrhythmia and an associated ventricular septal defect. Risk
      (hazard) of late death declined in the first decade, with further peaks in the
      second decade. Sinus rhythm was present in 77% at 5 years and 40% at 20 years.
      Loss of sinus rhythm was associated with previous septectomy, postoperative
      bradycardia and late atrial flutter. Freedom from atrial flutter was 92% at 5
      years and 73% at 20 years of age. Risk factors for atrial flutter were the
      occurrence of perioperative bradyarrhythmia, reoperation and loss of sinus rhythm
      during follow-up. Risk of atrial flutter demonstrates a late increase.
      CONCLUSIONS: Ongoing loss of sinus rhythm and late peaks in the risk of atrial
      flutter and death necessitate continued follow-up.

PMID- 8996315
TI  - Coronary artery obstruction after the arterial switch operation for transposition
      of the great arteries in newborns.
AB  - OBJECTIVES: We sought to describe a large series of coronary artery obstructions
      after the arterial switch operation for transposition of the great arteries and
      to discuss their clinical implications. BACKGROUND: Aortic root angiography and
      myocardial perfusion imaging yield ambiguous results regarding the fate of the
      coronary artery anastomoses after the arterial switch operation. Late death
      related to coronary artery obstruction and growth of the translocated coronary
      arteries are of major concern in these patients. METHODS: Selective coronary
      artery angiography was performed prospectively in a total of 165 children.
      RESULTS: A total of 12 coronary occlusions, 8 major stenoses, 6 minor stenoses of
      the left ostium and 4 stretchings of one coronary artery were identified.
      Obstructions were more frequent in types D and E (p < 0.001) of the Yacoub and
      Radley-Smith classification. Coronary obstruction was documented in all patients
      with electrocardiographic and ultrasound evidence of myocardial ischemia at time
      of study. Early postoperative ischemia did not predict coronary artery lesion if
      the patient had fully recovered. Persistent or delayed myocardial ischemia was
      highly predictive of coronary artery lesions. The incidence of coronary artery
      obstruction was very high (11 of 35) in patients operated on by a rapidly
      abandoned technique of single-orifice reimplantation of both coronary artery
      ostia. CONCLUSIONS: Selective coronary angiography is the most accurate means to
      assess coronary artery obstruction after the arterial switch operation. Precise
      diagnosis of coronary artery lesions after this operation will help to elucidate
      the pathogenesis, develop adequate therapeutic strategies and might indicate how
      to prevent coronary complications after operation.

PMID- 8996317
TI  - Do we practice geriatric cardiology?

PMID- 8996318
TI  - President's page: evaluation and management--the 51% solution.

PMID- 8996316
TI  - Myocardial contrast echocardiography in acute myocardial infarction using aortic
      root injections of microbubbles in conjunction with harmonic imaging: potential
      application in the cardiac catheterization laboratory.
AB  - OBJECTIVES: The aim of this study was to evaluate myocardial contrast
      echocardiography using aortic root injections with harmonic imaging in
      experimental acute myocardial infarction to determine the potential of this
      approach in the cardiac catheterization laboratory. BACKGROUND: It would be
      desirable to have an adjunctive procedure that could evaluate myocardial
      perfusion at the time of cardiac catheterization in patients with acute
      myocardial infarction. A single injection of contrast medium in the aortic root
      would provide complete information on myocardial perfusion in a cross section of
      the heart. High quality images would provide on-line assessment of myocardial
      perfusion without recourse to image processing. These data could be very valuable
      for determining patient management. METHODS: Perfusion defects on myocardial
      contrast echocardiography were measured during coronary occlusion and reflow,
      using fundamental and harmonic imaging in both continuous and intermittent modes
      in nine open chest dogs. These defects were compared with risk area on technetium
      99m autoradiography and infarct size on tissue staining. RESULTS: Whereas
      harmonic imaging increased myocardial video intensity by more than twofold (p <
      0.001) compared with fundamental imaging after aortic root injection of contrast
      medium, intermittent imaging was not superior to continuous imaging. The improved
      signal to noise ratio of harmonic imaging allowed on-line definition of risk area
      (r = 0.98) and infarct size (r = 0.93) without recourse to off-line processing.
      Similar results could be obtained with fundamental imaging only after off-line
      processing. CONCLUSIONS: Aortic root injection of contrast medium coupled with
      harmonic imaging can be used to provide accurate on-line assessment of risk area
      and infarct size during acute myocardial infarction. These results have important
      implications for the catheterization laboratory.

PMID- 8996319
TI  - Thrombolysis, the risk of rupture and other risks.

PMID- 8996320
TI  - Qualitative or quantitative assessment of spontaneous echo contrast?

PMID- 8996321
TI  - Risk for sudden cardiac death associated with marathon running.

PMID- 8996322
TI  - Late potentials in the thrombolytic era: time for reevaluation?

PMID- 8996323
TI  - "Prevalence" or "pretest likelihood" of coronary artery disease?

PMID- 8996324
TI  - Prediction of infarction by stress echocardiography.

PMID- 8996325
TI  - Measurement of atrial refractoriness dispersion: is there a better way?

PMID- 8996326
TI  - Current status of thermotherapy of the prostate.
AB  - PURPOSE: We reviewed the available data on transurethral microwave thermotherapy
      in the treatment of patients with benign prostatic hyperplasia (BPH). Furthermore
      we provide a perspective of this minimally invasive treatment modality. MATERIALS
      AND METHODS: To our knowledge all previously reported data from clinical trials
      of transurethral microwave thermotherapy for BPH are reviewed. RESULTS:
      Transurethral microwave thermotherapy was designed to apply microwave energy deep
      within lateral prostatic lobes while simultaneously cooling the urethral mucosa,
      thus enabling an outpatient based anesthesia-free procedure. Lower energy
      protocols using the Prostraton device provide significant symptomatic improvement
      and improvement in maximum flow of approximately 35% over baseline. Similar
      changes are being documented with other transurethral microwave thermotherapy
      devices. Higher energy protocols using the Prostatron device result in
      symptomatic improvement similar to that of lower energy protocols, while
      improvement in uroflowmetry is much more pronounced. However, the latter effect
      is achieved at the expense of increased morbidity. Second generation protocols
      have not yet been documented by users of the other thermotherapy devices.
      CONCLUSIONS: Numerous studies unequivocally support the efficacy and safety of
      transurethral microwave thermotherapy for treatment of symptomatic BPH.
      Significant improvement in objective and subjective parameters has been realized
      with transurethral microwave thermotherapy at multiple centers in the United
      States and Europe.

PMID- 8996327
TI  - Osteoporosis after orchiectomy for prostate cancer.
AB  - PURPOSE: The possibility of increased osteoporosis and osteoporotic fractures
      following therapeutic orchiectomy in men with prostate cancer was investigated.
      MATERIALS AND METHODS: A total of 235 men with nonstage A prostate cancer
      diagnosed between 1983 and 1990 was analyzed for therapeutic orchiectomy, other
      osteoporotic risk factors and subsequent hospital treatment for osteoporotic
      fractures. The 17 castrated men alive in 1995 were interviewed, and femoral neck
      bone mineral density was compared to that of 23 controls of similar age. RESULTS:
      Risk factors for osteoporosis, including smoking, slender habitus and atrophic
      testes, were common among men treated with orchiectomy. Of the men in the study
      cohort 10 had osteoporotic fractures: 8 of 59 treated with and 2 of 176 without
      orchiectomy (13.6 versus 1.1%, p < 0.001). First fracture cumulative incidence
      rates 7 years after castration or diagnosis were 28 and 1%, respectively (p <
      0.001). Osteoporotic fractures were much more common than pathological fractures
      or those due to major trauma (1 each). Bone mineral density averaged 0.91, 0.84,
      0.79 and 0.66 gm./cm.2 in 9 controls without prostate cancer, 14 men with
      prostate cancer before orchiectomy, 9 men at 9 to 60 and 8 men at 60 to 115
      months after orchiectomy, respectively. Of the 16 men surviving for longer than
      60 months after orchiectomy 6 had osteoporotic fractures, as did 5 of 6 and 5 of
      7 with a bone mineral density of less than 0.70 gm./cm.2 and less than 75% of
      normal for age, respectively. CONCLUSIONS: Orchiectomy for prostate cancer is
      frequently followed by severe osteoporosis, some of which had developed before
      castration. Appropriate therapy should be identified that does not diminish the
      antitumorigenic effectiveness of androgen ablation.

PMID- 8996328
TI  - Laparoscopic bilateral nephrectomy: results in 11 renal transplant patients.
AB  - PURPOSE: We report our experience with bilateral laparoscopic nephrectomy after
      renal transplantation. MATERIALS AND METHODS: Between August 1994 and October
      1995, 11 patients who had previously undergone renal transplantation underwent
      bilateral laparoscopic nephrectomy at our hospital due to poorly controlled
      hypertension. The records of 10 patients undergoing bilateral open nephrectomy
      were reviewed for comparison. RESULTS: Mean operative time in the laparoscopy
      group was 195 minutes (range 125 to 270). Mean blood loss was 345 ml. and 1
      patient required conversion to an open operation. Oral intake and mobilization
      were begun 1 day postoperatively. Mean postoperative morphine equivalent
      consumption was 14 mg., mean hospital stay was 4.2 days (range 3 to 6) and mean
      return to normal activities was 14 days. At a mean followup of 10.4 months blood
      pressure had improved significantly in 8 patients (73%). Mean operative time in
      the open surgery group was 145 minutes (range 115 to 170) and mean postoperative
      morphine equivalent required was 44 mg. Compared to the laparoscopy group the
      interval to resumption of oral intake (3.5 days), duration of hospital stay (10.7
      days) and return to normal activities (36 days) were prolonged in the open
      surgery group. CONCLUSIONS: According to our results, bilateral laparoscopic
      nephrectomy could be an effective alternative for the treatment of severe
      hypertension after renal transplantation. Compared to open nephrectomy most
      patients benefit from the laparoscopic approach.

PMID- 8996329
TI  - Lymphatogenous spread of renal cell carcinoma: an autopsy study.
AB  - PURPOSE: We investigated the occurrence and extent of metastatic spread,
      especially regarding lymph nodes, of renal cell carcinoma. MATERIALS AND METHODS:
      From 1958 to 1982, 554 cases of renal cell carcinoma were diagnosed at autopsy.
      Clinical data and autopsy findings were reevaluated, and the occurrence of lymph
      node metastases was analyzed by histological examination of retroperitoneal,
      mediastinal, supraclavicular, axillary and inguinal lymph nodes. RESULTS: Distant
      metastases were revealed in 119 cases (21.5%), including 31 (5.6%) with single
      metastases. In 88 cases (16%) renal cancer was the cause of death. Lymphatogenous
      dissemination was detected in 80 cases of which 75 had additional, mostly
      multifocal metastatic spread. Consequently lymph node metastases restricted to
      the paracaval and/or para-aortic lymph nodes were noted in only 5 cases (0.9%).
      CONCLUSIONS: Of the 554 cases of clinically unrecognized renal cell carcinoma
      almost all with lymphatic spread had additional distant metastases. Therefore,
      the therapeutic effect of extensive retroperitoneal lymph node dissection in
      association with radical nephrectomy seems to be low. However, more limited lymph
      node dissection may be useful, mainly as a staging procedure.

PMID- 8996330
TI  - Retrograde treatment of ureteropelvic junction obstruction using the ureteral
      cutting balloon catheter.
AB  - PURPOSE: We assessed the efficacy and safety of a new cutting balloon catheter to
      treat symptomatic ureteropelvic junction obstruction in adults. MATERIALS AND
      METHODS: A total of 32 adults (mean age 40 years, range 18 to 79) underwent
      retrograde balloon incision for symptomatic ureteropelvic junction obstruction
      (27 primary and 5 secondary cases). Treatment outcome was based on improvement of
      symptoms and resolution of obstruction by excretory urography or diuretic renal
      scintigraphy. RESULTS: A total of 36 retrograde endopyelotomies was performed on
      32 patients. Of 4 patients who underwent repeat endopyelotomy 2 had resolution of
      persistent obstruction. At a mean followup of 14 months (range 3 to 28) 28 of 32
      patients (87.5%) were rendered symptom-free and had no obstruction on excretory
      urography or diuretic renography. Average hospital stay was 1.8 days (range 0 to
      6) and the complication rate was 15.6% (postoperative bleeding, fever and ileus).
      Treatment failed in 4 patients and subsequent open pyeloplasty was successful.
      CONCLUSIONS: Retrograde balloon incision endopyelotomy appears to be a safe and
      effective treatment for ureteropelvic junction obstruction.

PMID- 8996331
TI  - Laparoscopic pyeloplasty: experience with the initial 30 cases.
AB  - PURPOSE: We assessed the intermediate effectiveness of laparoscopic pyeloplasty
      in the treatment of the obstructed ureteropelvic junction. MATERIALS AND METHODS:
      A total of 30 pyeloplasties was performed for symptomatic ureteropelvic junction
      obstruction (24 primary and 6 secondary cases). Two separate types of
      reconstruction were performed, that is dismembered (26 patients) and Y-V (4)
      pyeloplasty. All patients were followed with excretory urography or diuretic
      renography. Moreover, factors affecting the learning curve (surgical technique,
      prior laparoscopic experience and cause of obstruction) were evaluated. RESULTS:
      A lower pole segmental renal vessel was found at the ureteropelvic junction in 18
      patients (60%). Operative time ranged from 2.25 to 8.0 hours (mean 4.5).
      Postoperative morbidity (mean narcotic requirement 37.3 mg. morphine sulfate,
      mean hospital stay 3.5 days and convalescence 3 weeks) was minimum. At
      radiographic followup (mean 16.3 months, range 4 to 73) 97% of the patients
      demonstrated a patent ureteropelvic junction and resolution of or substantial
      decrease in hydronephrosis. CONCLUSIONS: In the hands of an experienced
      laparoscopist, outcomes indicate that laparoscopic pyeloplasty shows success
      similar to that of open pyeloplasty but longer term outcomes must be assessed.

PMID- 8996332
TI  - The role of laparoscopy in the treatment of renal and ureteral calculi.
AB  - PURPOSE: We assessed the efficacy of laparoscopy in the treatment of renal and
      ureteral stones. MATERIALS AND METHODS: Laparoscopic stone extraction was
      attempted in 11 men and 6 women 22 to 75 years old, including 6 with ureteral and
      11 with renal calculi. Of the renal stones 9 were associated with a concomitant
      pathological condition requiring surgery. Four patients had multiple stones (2 to
      93) and stone size ranged from 2 to 60 mm. (mean 15.6). RESULTS: Stones from 15
      of 17 patients were removed successfully via laparoscopic techniques. Operative
      time ranged from 2.33 to 6.35 hours (mean 4.9). Prolonged operating times were
      associated with ancillary or failed procedures. Blood loss ranged from 20 to 350
      ml. (mean 132.9), narcotic requirement from 0 to 100 mg. morphine (mean 26) and
      hospital stay from 1 to 15 days (mean 4.5). The 3 postoperative complications
      included prolonged ileus (2) and a retroperitoneal urinoma requiring secondary
      drainage. CONCLUSIONS: Laparoscopic stone removal is safe and feasible.
      Indications for this approach include urinary stones associated with an
      anatomical abnormality requiring urinary tract reconstruction and calculi for
      which other minimally invasive therapies failed.

PMID- 8996333
TI  - Should open pyeloplasty be abandoned?

PMID- 8996334
TI  - Ureteral anastomosis in the orthotopic ileal neobladder: comparison of 2
      techniques.
AB  - PURPOSE: The functional results and complications of 2 different ureteroileal
      anastomoses were evaluated in patients with bladder cancer undergoing radical
      cystectomy and orthotopic ileal bladder substitution. MATERIALS AND METHODS:
      Between 1989 and 1995, 102 patients underwent creation of a low pressure
      neobladder. In the first 50 cases the ureteroileal anastomosis was created with a
      split-cuff nipple technique as an additional antireflux mechanism. In the next 52
      cases the ureteroileal anastomoses were constructed via the direct end-to-side
      technique counting on the antireflux protection of the afferent tubular limb.
      RESULTS: Stenosis occurred in 7 of the 100 ureters (6 patients) treated with the
      split-cuff nipple technique and 7 of 104 treated with a direct end-to-side
      anastomosis. This complication occurred more commonly in the left ureter (11 of
      14 patients). Reflux was noted at cystography in 10 cases with the split-cuff
      nipple method and 12 with end-to-side anastomoses, and was symptomatic in only 3
      patients. Four ureteral strictures were treated successfully with primary open
      repair. Percutaneous dilation and stenting were performed for 8 ureteral
      strictures: 2 cases were successful, 3 failed and 3 are unresolved. CONCLUSIONS:
      We observed no differences between the antireflux split-cuff and end-to-side
      anastomoses with regard to stricture formation or ureteral reflux. Therefore, we
      do not believe that there is a need to create antireflux ureteral anastomoses due
      to the tubular afferent ileal segment and given that the reflux is asymptomatic
      in most patients. Strictures may be treated with percutaneous balloon dilation
      and stenting but open repair appeared to be more effective.

PMID- 8996336
TI  - Urinary tract reconstruction.

PMID- 8996335
TI  - Combined reconstructive and prosthetic surgery in complicated lower urinary tract
      dysfunction.
AB  - PURPOSE: The combined use of the appropriate reconstructive technique and
      available prosthetic material was evaluated to achieve an optimal functional
      result in complicated lower urinary tract dysfunction. MATERIALS AND METHODS: The
      study included 16 male and 8 female patients. Urinary dysfunction was classified
      into 2 main categories: 1) neuropathic and 2) nonneuropathic. Of the patients 22
      underwent some form of augmentation (21) or substitution (1) cystoplasty, 24
      received an artificial urinary sphincter, 2 underwent abdominoperineal
      urethroplasty and 2 received a permanent urethral stent. One patient underwent
      renal transplantation and 1 received a penile prosthesis for concurrent
      impotence. RESULTS: A total of 20 patients (83.3%) became continent, 10 void
      spontaneously, while 14 must empty the bladder or pouch by clean intermittent
      self-catheterization. All patients have stable or improved renal function.
      CONCLUSIONS: Combined reconstructive and prosthetic surgery has an important role
      in the treatment of lower urinary tract dysfunction, with a high success rate and
      good quality of life.

PMID- 8996338
TI  - Is routine excretory urography necessary at first diagnosis of bladder cancer?
AB  - PURPOSE: We determined whether routine excretory urography (IVP) at initial
      diagnosis of bladder cancer is useful in screening the upper urinary tract for
      clinically inapparent urothelial tumors. MATERIALS AND METHODS: IVPs and
      ultrasound findings of 314 patients with bladder cancer were reviewed
      retrospectively. RESULTS: Only 1 silent upper urinary tract tumor was detected
      with IVP (0.3%), resulting in nephroureterectomy. IVP had no further therapeutic
      consequences except for destruction of an asymptomatic prevesical stone. IVP was
      followed by ureterorenoscopy in 5 patients with negative results. Upper urinary
      tract obstruction could be documented equally well by sonography in all cases.
      CONCLUSIONS: Routine IVP at first diagnosis of bladder cancer is unnecessary.

PMID- 8996337
TI  - Noninvasive quantitative estimation of infravesical obstruction using ultrasonic
      measurement of bladder weight.
AB  - PURPOSE: Ultrasound estimated bladder weight was compared to pressure-flow
      studies to test the ability of ultrasound estimated bladder weight to predict
      infravesical obstruction. MATERIALS AND METHODS: A total of 65 men with urinary
      symptoms underwent ultrasonic measurement of bladder weight and pressure-flow
      studies. Assuming the bladder is a sphere, ultrasound estimated bladder weight
      was calculated from bladder wall thickness measured ultrasonically and
      intravesical volume. RESULTS: Ultrasound estimated bladder weight correlated
      significantly (p < 0.0001) with the Abrams-Griffiths number, urethral resistance
      factor and the Schafer grade of obstruction. A cutoff value of 35 gm. for
      ultrasound estimated bladder weight revealed a diagnostic accuracy of 86.2% (56
      of 65 cases) for infravesical obstruction with 12.1 (4 of 33) and 15.6% (5 of 32)
      false-positive and false-negative rates, respectively. CONCLUSIONS: Ultrasound
      estimated bladder weight can be measured noninvasively at the bedside and it is
      promising as a reliable predictor of infravesical obstruction.

PMID- 8996339
TI  - Tumors in bladder remnant after augmentation enterocystoplasty.
AB  - PURPOSE: We attempted to determine the tissue of origin of tumors after
      augmentation enterocystoplasty. MATERIALS AND METHODS: We retrospectively
      reviewed the histological findings of 4 tumors that developed after clam
      ileocystoplasty. RESULTS: Tumors were primarily adenocarcinoma that originated on
      the bladder side of the anastomosis. The urothelium showed glandular metaplasia
      and dysplasia with intestinalization overlying normal detrusor muscle. These
      changes were also present in the renal pelvis in 1 patient with ureteral reflux.
      Bowel mucosa was normal except for inflammation. CONCLUSIONS: These tumors are
      derived from urothelium, which may be due to elevated urinary nitrosamines in
      this group of patients.

PMID- 8996340
TI  - A 12 versus 6-week course of bacillus Calmette-Guerin prophylaxis for the
      treatment of high risk superficial bladder cancer.
AB  - PURPOSE: We examined the efficacy of a 12-week prophylactic course of bacillus
      Calmette-Guerin (BCG) on superficial bladder cancer. MATERIALS AND METHODS: From
      August 1992 until July 1994, 70 evaluable patients 41 to 80 years old (mean age
      68.5) with high risk transitional cell carcinoma of the bladder were
      prospectively randomized to a 12-week prophylactic course of BCG (group 2) versus
      a traditional 6-week course (group 1). Mean followup was 28 months. RESULTS: A
      70% tumor-free rate (21 patients) and mean interval of 12.9 months to recurrence
      were achieved in group 2 compared to 55% (22 patients) and 12.3 months,
      respectively, in group 1. Group 2 patients had an overall longer disease-free
      survival, although no statistical significance was achieved. A subgroup of
      patients with stage Ta cancer in whom at least 1 tumor was resected 12 month
      before treatment showed the most benefit from long-term prophylactic treatment in
      terms of disease-free survival. Side effects were only slightly more prominent in
      group 2, rendering the longer course fairly acceptable. CONCLUSIONS: Our findings
      suggest a difference for better overall results with the 12-week course of BCG.
      However, a larger number of patients are needed to demonstrate a statistically
      significant difference between the 2 groups.

PMID- 8996341
TI  - Evolution and clinical significance of the T cell proliferative and cytokine
      response directed against the fibronectin binding antigen 85 complex of bacillus
      Calmette-Guerin during intravesical treatment of superficial bladder cancer.
AB  - PURPOSE: The antitumorigenic effect of intravesical bacillus Calmette-Guerin
      (BCG) in superficial bladder cancer was reported to be initiated by the
      attachment of BCG to the bladder wall via fibronectin. The antigen 85 complex
      secreted in BCG culture filtrate binds specifically to fibronectin and is a
      powerful T cell stimulus. Therefore, we investigated the evolution and clinical
      significance of the cellular proliferative response and cytokine production
      during intravesical BCG therapy against this purified antigen 85 complex.
      MATERIALS AND METHODS: Evolution of the lymphoproliferation, interleukin-2 and
      interferon-gamma production of peripheral blood lymphocytes against tuberculin
      (purified protein derivative), purified antigen 85, BCG culture filtrate, whole
      BCG bacilli and pokeweed mitogen was tested before and after 6 weekly
      intravesical BCG instillations in 29 patients with superficial bladder cancer at
      intermediate or high risk for recurrence. RESULTS: A major increase in the
      lymphoproliferative response against purified protein derivative, antigen 85, BCG
      culture filtrate, whole BCG and pokeweed mitogen was observed in 69.0, 65.5,
      79.3, 48.3 and 65.3% of the patients, respectively, analyzed after BCG therapy.
      Reactivity returned to baseline values at 6 months of followup. Of the patients
      who received a second BCG course because of tumor recurrence 66% had a novel
      increase in lymphoproliferation against antigen 85. An increase in the production
      of interleukin-2 and interferon-gamma by peripheral lymphocytes against antigen
      85 was noted in 42.1 and 50% of the treated patients, respectively, after a
      single BCG course. During a mean followup of 23.11 months 48.5% of the patients
      remained tumor-free. No correlation could be found between the immunological
      response against any of the BCG antigens and the clinical evolution of the
      response. CONCLUSIONS: Intravesical BCG instillations induce a transient (less
      than 6 months) peripheral immune activation against several purified BCG antigens
      and among them the fibronectin binding antigen 85 complex. Reactivation is
      observed in most cases after additional BCG courses. The absence of long lasting
      immune activation after a single 6-week course of BCG could be related to the
      increased clinical efficacy observed with BCG maintenance instillations.

PMID- 8996343
TI  - Reconstruction of posterior urethral disruption injuries: outcome analysis in 82
      patients.
AB  - PURPOSE: We sought to identify the long-term success rate of perineal anastomotic
      reconstruction for posterior urethral disruption. MATERIALS AND METHODS: We
      reviewed the records of 82 patients with traumatic prostatomembranous urethral
      strictures who underwent perineal anastomotic urethroplasty by 1 surgeon.
      RESULTS: Excision of fibrosis with simple perineal anastomosis was performed in
      52 patients (63%), while pubectomy was required in 30 (37%) to obtain a tension
      free anastomosis. Median followup was longer than 1 year. Potency improved from
      46% before reconstruction to 62% postoperatively. Nine patients (11%) required 1
      endoscopic urethrotomy after urethroplasty to improve flow rate and this
      procedure was successful in 8 (88%). In 3 patients (3%) urethroplasty ultimately
      failed and they remained untreated because of insurmountable co-morbidity.
      Overall, long-term success was observed in 79 patients (97%). CONCLUSIONS:
      Excellent long-term results can be expected from anastomotic urethroplasty in
      patients with traumatic posterior urethral strictures. Subsequent urethrotomy,
      when required, has a high likelihood of success. A significant number of patients
      regain potency after urethral reconstruction. Persistent impotence probably
      reflects the severity of pelvic trauma.

PMID- 8996342
TI  - Posttraumatic posterior urethral stricture repair: anatomy, surgical approach and
      long-term results.
AB  - PURPOSE: We describe the anatomy, surgical approach and long-term results of
      posterior urethral stricture repair. MATERIALS AND METHODS: Between 1975 and
      1991, 86 patients underwent surgery for posttraumatic posterior urethral
      stricture. In 65 patients the urethral lesion was corrected by 1-stage
      reconstructive surgery via the perineal approach. In 21 patients the urethra was
      reconstructed with a 2-stage procedure. In an anatomical study the course of the
      urethra through the pelvic floor was investigated and the concomitant structures
      were dissected. According to the anatomy a perineal approach was used in 7 male
      adult cadavers. RESULTS: Due to the optimized anastomotic technique urinary flow
      rates of more than 20 ml. per second could be achieved in 29 of all 42 patients
      followed. Only 6 of these patients had peak urinary flow rates of less than 15
      ml. per second. No patient had any recurrent strictures at the anastomotic site
      that would have required surgical revision. CONCLUSIONS: Our results suggest that
      adequate primary care and the perineal approach combined with an exact
      anastomosis technique are essential for successful treatment of posttraumatic
      strictures of the posterior urethra.

PMID- 8996344
TI  - The management of traumatic posterior urethral distraction defects.

PMID- 8996345
TI  - Oral desmopressin as a new treatment modality for primary nocturnal enuresis in
      adolescents and adults: a double-blind, randomized, multicenter study. Dutch
      Enuresis Study Group.
AB  - PURPOSE: We evaluated the efficacy and safety of 2 oral doses of desmopressin
      compared to 20 micrograms. nasal spray and baseline values in the treatment of
      primary nocturnal enuresis. MATERIALS AND METHODS: A multicenter study was done
      comparing oral dosages (200 and 400 micrograms.) of desmopressin (4-week,
      randomized, double-blind phase followed by 12 weeks of open label treatment with
      400 micrograms.) to 20 micrograms. nasal spray in 66 adults and adolescents 12 to
      45 years old with primary nocturnal enuresis. RESULTS: No significant differences
      were found between the 2 doses of desmopressin tablets or between the tablets and
      20 micrograms. nasal spray during the double-blind phase. However, patients who
      initially received 200 micrograms. desmopressin tablets experienced fewer wet
      nights after they completed 12 weeks of open label treatment when the dose was
      escalated to 400 micrograms. tablets. Those who received 400 micrograms. tablets
      initially maintained response during this phase. Desmopressin tablets were well
      tolerated at both dose levels: 96% of patients and 94% of physicians rated the
      tolerability as excellent. CONCLUSIONS: Desmopressin tablets are an effective and
      safe alternative for treatment of nocturnal enuresis.

PMID- 8996346
TI  - Vasectomy reversal for treatment of the post-vasectomy pain syndrome.
AB  - PURPOSE: The post-vasectomy pain syndrome is a rare but troublesome complication
      of vasectomy. We report our experience with 32 patients who underwent vasectomy
      reversal for relief of the post-vasectomy pain syndrome. MATERIALS AND METHODS:
      The records of 32 patients undergoing vasovasostomy or epididymovasostomy for the
      post-vasectomy pain syndrome were evaluated for characteristics of symptoms,
      previous therapy, interval from vasectomy, success of surgery and duration of
      relief. RESULTS: Of 32 men who underwent vasectomy reversal for the post
      vasectomy pain syndrome between 1980 and 1994, 24 had relief of symptoms after
      the initial procedure. Of 8 men with recurrent pain 6 underwent a second reversal
      procedure, and 3 of them subsequently had relief of symptoms. Overall, 27 of 32
      men had resolution of pain. CONCLUSIONS: In our experience vasectomy reversal has
      a high rate of success for relief of the post-vasectomy pain syndrome. It does
      not preclude other forms of surgical therapy and it should be considered in the
      treatment of the post-vasectomy pain syndrome.

PMID- 8996347
TI  - Effect of artificial stimulants on cryopreserved spermatozoa from cancer
      patients.
AB  - PURPOSE: We determined whether cryopreserved sperm samples obtained from cancer
      patients before treatment respond to artificial motility stimulants and if this
      response is related to the extent of disease. MATERIALS AND METHODS: Pre-freeze
      distribution of disease stage in the different types of cancer and the percentage
      of the population with or without oligospermia before cryopreservation were
      examined. Cryopreserved semen samples from 17 cancer patients (10 with testicular
      cancer, 5 with Hodgkin's disease and 2 with other metastatic disease) were
      examined for a relationship between post-thaw sperm motion characteristics and
      patient age or status (survived versus died) and type of disease. Motion
      characteristics (curvilinear velocity, straight line velocity, average path
      velocity, linearity and amplitude of lateral head displacement) were analyzed on
      a computer assisted semen analyzer before (time 0), and 30 and 60 minutes after
      addition of a 2.5 mM. concentration of pentoxifylline and 2-deoxyadenosine.
      RESULTS: Post-thaw sperm motion characteristics were not correlated with patient
      age or status, whether they did or did not have oligospermia, or type of cancer.
      Compared to baseline values, sperm motion characteristics increased significantly
      after stimulation at time 0 (p < 0.02) and at 60 minutes (p < 0.05). Oligospermic
      or nonoligospermic specimens responded to the same extent with pentoxifylline and
      2-deoxyadenosine. A negative correlation was noted between overall stage, and
      type of disease and motion characteristics. CONCLUSIONS: Sperm banking should be
      encouraged at cancer diagnosis regardless of semen quality. Artificial
      stimulation of sperm motility results in significant improvement in sperm motion
      characteristics.

PMID- 8996348
TI  - Doxazosin for benign prostatic hyperplasia: long-term efficacy and safety in
      hypertensive and normotensive patients. The Multicenter Study Group.
AB  - PURPOSE: We evaluated the sustained efficacy and safety of doxazosin for long
      term treatment (up to 48 months) of normotensive and hypertensive patients with
      benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 272
      normotensive and 178 mildly to moderately hypertensive men entered a long-term
      extension study of doxazosin therapy (1 to 8 and 1 to 12 mg. 1 time daily,
      respectively) for BPH following participation in double-blind, placebo controlled
      studies. The starting dose of doxazosin was 1 mg. with upward titrations at 2
      week intervals to a stable, efficacious and well tolerated dose. At the time of
      data analysis patients had received between 1 and 48 months of stable dose
      doxazosin therapy (mean 668 days for normotensive and 807 for hypertensive
      patients). Mean daily doses were 4 and 6.4 mg. for normotensive and hypertensive
      men, respectively. RESULTS: At the end point analysis doxazosin treatment
      resulted in significant increases above baseline in maximum and average urinary
      flow rates (1.9 and 1.0 ml. per second, respectively). As assessed by the
      patient, total, obstructive and irritative BPH symptoms also improved
      significantly with doxazosin treatment. In the 28 patients who completed 45 to 48
      months of treatment improvement in symptom bothersomeness (13.2%) was similar to
      that of the overall group at the end point (14.8%). Sustained blood pressure
      decreases (approximately 8/11 mm. Hg systolic/diastolic blood pressure) with
      doxazosin were statistically and clinically significant in hypertensive patients.
      Blood pressure decreases in normotensive patients were not clinically significant
      (approximately 4/2 mm. Hg) and few withdrew from study for reasons related
      directly to decreased blood pressure or hypotension. Changes in heart rate were
      not significant. Doxazosin was well tolerated with almost 90% of adverse
      experiences considered mild or moderate in severity. The most common adverse
      events were dizziness, headache and fatigue in normotensive and hypertensive
      patients. CONCLUSIONS: In this study long-term doxazosin treatment was
      significantly effective and well tolerated for treating BPH in normotensive and
      hypertensive patients.

PMID- 8996349
TI  - The safety of overnight hospitalization for transurethral prostatectomy: a
      prospective study of 200 patients.
AB  - PURPOSE: Our goal was to determine the appropriateness, safety and cost
      effectiveness of catheter removal and hospital discharge 1 day after
      transurethral prostatectomy. MATERIALS AND METHODS: A prospective study of 200
      patients who underwent transurethral prostatectomy during a 23-month period was
      done. On the morning of postoperative day 1 catheters were removed from 156
      patients (78%) who had normal vital signs, adequate urine output, absence of
      clots and acceptable character of the catheter effluent. RESULTS: Among the 156
      patients whose catheters were removed 4 of 5 went home on postoperative day 1.
      Two of these patients were rehospitalized within 30 days, as were 2 others whose
      catheters were removed later. Overall length of patient stay was 1.6 days.
      CONCLUSIONS: Overnight hospitalization after transurethral prostatectomy is an
      appropriate, safe and cost-effective pathway of patient care that is readily
      applicable to any urology practice.

PMID- 8996350
TI  - Predictors of general quality of life in patients with benign prostate
      hyperplasia or prostate cancer.
AB  - PURPOSE: Studies in disease specific populations have emphasized disease specific
      quality of life with little study of general quality of life. Furthermore,
      studies of general quality of life in disease specific populations have mostly
      examined the importance of disease specific variables, and have generally yielded
      poor correlations of such variables and general quality of life. We attempted to
      model the emotional component of general quality of life in patients with
      prostate disease. MATERIALS AND METHODS: We integrated prospectively collected
      disease specific and nonspecific clinical and self-reported patient data. We also
      applied neural network and more conventional statistical tools to examine the
      relative use of various available analytical methodologies in modeling general
      quality of life. RESULTS: Neural networks created reasonably good models of the
      emotional component of general quality of life. Logistic regression analysis also
      created reasonably good models and, given current computational schemes, allowed
      for identification of significant inputs in the models more readily than did the
      feed-forward, back propagation neural networks. All models of general quality of
      life relied primarily on disease nonspecific inputs, including social support,
      activities of daily living and coping. CONCLUSIONS: Our observations suggested
      that efforts to optimize general quality of life in patients with prostate
      disease must integrate disease nonspecific variables.

PMID- 8996351
TI  - Correlation between bone metabolic markers and bone scan in prostatic cancer.
AB  - PURPOSE: We examined the correlation between bone metabolic markers and bone
      scintigraphy in prostatic cancer. MATERIALS AND METHODS: Osteoblastic and
      osteoclastic markers, prostate specific antigen (PSA) and bone scans were
      investigated in 83 specimens from 70 patients with prostatic cancer, including 32
      with and 38 without bone metastasis. RESULTS: All markers except for osteocalcin
      were significantly greater in patients with than without bone metastasis.
      Pyridinoline cross-linked carboxyterminal telopeptide, an osteoclastic marker,
      reflected the extent of bone metastasis more accurately than PSA and other bone
      markers. CONCLUSIONS: Pyridinoline cross-linked carboxyterminal telopeptide might
      assist PSA and bone scintigraphy in monitoring metastatic bone activity of
      prostatic cancer.

PMID- 8996352
TI  - The free-to-total serum prostate specific antigen ratio for staging prostate
      carcinoma.
AB  - PURPOSE: We analyzed the relationship between the free-to-total PSA ratio and
      prostate cancer tumor stage and grade compared to total serum PSA. MATERIALS AND
      METHODS: In 123 patients clinical and pathological grade and stage were related
      to total serum PSA and free-to-total PSA ratio. RESULTS: Total serum PSA
      paralleled clinical staging of prostate cancer. The distributions of total serum
      PSA and the free-to-total PSA ratio were significantly different between benign
      and malignant diseases (any stage), and between any T category and nodal disease.
      For serum PSA significant differences were noted between the distributions of men
      with locally confined (stages T1 and T2) and locally extended (stage T3) disease,
      and between all T categories and systemic metastatic disease. This finding was
      not noted for the free-to-total PSA ratio. CONCLUSIONS: The free-to-total PSA
      ratio has no additional value in clinical staging of prostate carcinoma compared
      to serum PSA. The free-to-total PSA ratio may be considered the result of cell
      differentiation and not an indicator of tumor load.

PMID- 8996353
TI  - Laparoscopic pelvic lymph node dissection following definitive radiotherapy for
      carcinoma of the prostate.
AB  - PURPOSE: Laparoscopic pelvic lymph node dissection is an effective and minimally
      invasive approach to the clinical staging of adenocarcinoma of the prostate. We
      report our experience with this technique in patients in whom full course pelvic
      radiotherapy had failed and who were being considered for salvage local therapy.
      MATERIALS AND METHODS: In 14 patients disease was staged by transperitoneal
      laparoscopic pelvic lymph node dissection performed for persistent adenocarcinoma
      of the prostate at least 20 months (average 49.5) following external beam
      radiotherapy and/or brachytherapy. All patients were healthy, had no evidence of
      metastatic disease and were considered to be candidates for salvage therapy.
      RESULTS: A total of 13 patients underwent successful laparoscopic pelvic lymph
      node dissection while 1 sustained an enterotomy requiring conversion to open
      surgery. The normal surgical planes were more difficult to dissect, with the
      obturator lymph node packets appearing smaller and more fibrotic than in
      nonirradiated patients, yielding an average of 7.1 total nodes. Average operative
      time was 167 minutes and postoperative hospitalization was comparable to reported
      series of nonirradiated patients. Four patients (28%) with metastatic pelvic
      lymph nodes underwent subsequent orchiectomy. Nine patients with negative lymph
      nodes underwent ultrasound guided transperineal placement of radioactive gold or
      palladium seeds. One patient underwent salvage radical retropubic prostatectomy.
      CONCLUSIONS: Laparoscopic pelvic lymph node dissection following full course
      pelvic irradiation is technically feasible, albeit more difficult than in
      nonirradiated patients. This approach appears to be an excellent minimally
      invasive technique for the clinical restaging of persistent adenocarcinoma of the
      prostate in patients being considered for salvage therapy.

PMID- 8996354
TI  - Histological presence of viable prostatic glands on routine biopsy following
      cryosurgical ablation of the prostate.
AB  - PURPOSE: Cryosurgical ablation of the prostate has recently received much
      attention as a therapeutic alternative for the treatment of localized prostatic
      adenocarcinoma. Biopsies after treatment reveal a variety of dysplastic changes
      as well as unaltered prostatic glandular epithelial elements. Prostate specific
      antigen (PSA) remains undetectable in the majority of men. However, in some PSA
      increases without demonstrable local recurrence. MATERIALS AND METHODS: A total
      of 383 patients underwent 447 procedures between June 1990 and January 1994. Of
      358 biopsies performed at our institution, 317 (2,075 cores) were available for
      review. Each core was examined for unaltered prostatic glandular epithelial
      elements and then scored for the percentage of epithelial glandular involvement
      according to a scale of: 0-no, 0.5-less than 10%, 1-10 to 25%, 2-25 to 50%, 3-50
      to 75% and 4-76 to 100% unaltered prostatic glandular epithelial elements.
      RESULTS: Of 317 biopsies 158 (49.8%) contained no unaltered prostatic glandular
      epithelial elements, while 185 (58.3%) and 206 (65%) had 1 core containing 10%
      and 10 to 25%, respectively, of such elements. Of 262 cases (82.6%) with a mean
      of 10% unaltered prostatic glandular epithelial elements per core 22 (8.4%) were
      positive for residual carcinoma. Among 55 cases with more normal epithelium per
      core 24 (43.6%) were positive for residual carcinoma. Patients with a positive
      biopsy had a median PSA of 2.02 ng./ml. (average gland/core score 0.54). Median
      PSA for men with negative biopsies was 0.2 ng./ml. (gland/core score 0.124).
      CONCLUSIONS: Cryosurgical ablation of the prostate has the ability to ablate
      prostatic tissue completely, thus rendering it free of glandular elements as
      determined by biopsy. Increasing PSA can indicate residual glandular elements.
      Increases in unaltered prostatic glandular epithelial elements with time are not
      paralleled by increased rates of local disease recurrence. undetectable serum PSA
      has a low risk of residual unaltered prostatic glandular epithelial elements and
      localized carcinoma. Results as measured by unaltered prostatic glandular
      epithelial elements and PSA improve with the surgical experience.

PMID- 8996355
TI  - Indications for transition zone biopsy in the detection of prostatic carcinoma.
AB  - PURPOSE: We determined the indications for transition zone biopsy in the
      detection of prostatic carcinoma. MATERIALS AND METHODS: A total of 185 men
      underwent 204 transition zone prostate biopsies due to elevated prostate specific
      antigen (PSA) alone in 19 (group 1), with hypoechoic transition zone lesions in
      10 (group 2) and with a previous negative transrectal ultrasound guided biopsy in
      156 (group 3). In addition, 13 men underwent 19 repeat transition zone biopsies.
      RESULTS: Of the patients 58 (31.4%) had positive biopsies, with 8 (4.3%) having
      cancer in the transition zone biopsies only. In 3 men with positive peripheral
      and transition zone biopsies the cancer was upgraded based on the transition zone
      specimens. No patient with elevated PSA and no previous biopsy (group 1) or
      sonographic transition zone abnormalities (group 2) had a positive transition
      zone biopsy only. None of the analyzed risk factors (age, PSA, prostate volume,
      PSA density or PSA velocity) was significantly greater in men with isolated
      transition zone tumors. CONCLUSIONS: Routine transition zone biopsies should be
      reserved for patients with previously negative transrectal ultrasound guided
      biopsies. In some patients disease upgrading based on transition zone biopsies
      may influence treatment decisions.

PMID- 8996356
TI  - Correlation between Gleason score of needle biopsy and radical prostatectomy
      specimen: accuracy and clinical implications.
AB  - PURPOSE: Despite the reliability of Gleason grading with respect to the same
      specimen, the correlation between the biopsy and prostatectomy specimen is less
      well defined. We compared the accuracy of Gleason grading of biopsies in
      predicting histological grading of radical retropublic prostatectomy specimens.
      MATERIAL AND METHODS: Gleason scores of 18 gauge needle biopsies were compared to
      those of radical retropublic prostatectomy specimens in 226 consecutive patients.
      In addition to comparing numeric discrepancies, differences between biopsy and
      specimen Gleason scores of 2 or more and a change in group from Gleason scores 2
      to 4, 5 to 7 or 8 to 10 were evaluated by kappa testing, as well as any change in
      group from Gleason scores 2 to 4, 5 and 6, 7 and 8 to 10. RESULTS: The biopsy
      score was identical to the specimen score in 31% of cases, while 26% were
      discrepant by 2 or more Gleason scores. Overall, 54% of biopsies were under
      graded, while 15% were over graded. If only cases in which discrepancies of 2 or
      more Gleason scores and a change in group were considered, there was good overall
      agreement (kappa 0.468, accuracy 80%). Among the cases with any change in group,
      the accuracy was only 46% with poor agreement (kappa 0.153). CONCLUSIONS:
      Overall, the reliability of Gleason grading of needle biopsies in predicting
      final pathology was good. However, the limitations of Gleason grading based on
      biopsy should be considered when discussing treatment options and comparing
      results based on biopsy data.

PMID- 8996357
TI  - Prostate cancer.

PMID- 8996358
TI  - Plasma chromogranin A in prostatic carcinoma and neuroendocrine tumors.
AB  - PURPOSE: Chromogranin A is a good tumor marker for neuroendocrine cells. Whether
      plasma chromogranin A could be a useful marker for neuroendocrine differentiation
      of prostatic carcinoma and neuroendocrine tumors was investigated using an enzyme
      linked immunosorbent assay. MATERIALS AND METHODS: Plasma levels of chromogranin
      A were measured by enzyme-linked immunosorbent assay in 33 patients with
      prostatic carcinoma, 10 with benign prostatic hyperplasia (BPH) and 13 with
      neuroendocrine tumors (2 medullary thyroid carcinomas, 1 thymic carcinoid, 1
      gastrin producing duodenal carcinoid, 3 nonfunctioning pancreatic endocrine
      tumors, 2 neuroblastomas, 3 pheochromocytomas and 1 carotid body tumor). RESULTS:
      The normal level of chromogranin A from 40 healthy volunteers was 30 +/- 11 units
      per 1. (mean plus or minus standard deviation). Mean plasma chromogranin A in
      patients with BPH and prostatic carcinoma was 52.4 +/- 12.9 and 67.5 +/- 22.9
      units per 1., respectively. All patients with neuroendocrine tumors, except 1
      with a nonfunctioning pancreatic endocrine tumor, had elevated chromogranin A
      (mean 401 +/- 409 units per 1.). There were significant differences in plasma
      chromogranin A level between patients with BPH and neuroendocrine tumors (p <
      0.01), prostatic carcinoma and neuroendocrine tumors (p < 0.01), and BPH and
      prostatic carcinoma (p < 0.05). Of the 33 patients with prostatic carcinoma 5 had
      elevated chromogranin A, only 1 of whom had elevated prostate specific antigen.
      CONCLUSIONS: Chromogranin A is an excellent marker for neuroendocrine tumors,
      particularly nonfunctioning tumors, and measurement of chromogranin A is also
      useful to detect prostatic carcinoma in patients whose prostate specific antigen
      is not elevated.

PMID- 8996359
TI  - Expression of bcl-2 oncoprotein and p53 protein accumulation in bone marrow
      metastases of androgen independent prostate cancer.
AB  - PURPOSE: We correlated the expression of bcl-2 with accumulation of p53 protein
      in bone marrow metastases from patients with androgen independent prostate cancer
      and a history of hormonal ablation therapy. These results were correlated with
      clinical parameters, including the extent of bone marrow metastases and patient
      survival. MATERIALS AND METHODS: All 43 patients studied had evidence of prostate
      cancer progression following androgen deprivation therapy and histologically
      confirmed bone marrow metastases. Decalcified tissue sections were used for
      immunohistochemical evaluation of bcl-2 protein and p53 protein accumulation.
      RESULTS: We previously established that p53 protein accumulation as detected by
      immunohistochemistry is a reliable indicator of p53 gene mutation in prostate
      cancer. Immunoreactivity was demonstrated for p53 protein in 22 of 43 cases and
      for bcl-2 protein in 14. A total of 28 cases (65%) exhibited immunohistochemical
      evidence of p53 and/or bcl-2 expression, and 15 (35%) were negative for p53 and
      bcl-2. The expression of bcl-2 and accumulation of p53 were independent events (p
      < 0.01). The expression of bcl-2 or accumulation of p53 protein in prostate
      cancer metastases did not significantly influence patient survival or the extent
      of metastatic disease. CONCLUSIONS: The presence or absence of p53 protein
      accumulation and/or bcl-2 expression did not correlate with tumor burden or
      patient survival in stage D androgen independent prostate cancer bone marrow
      metastases. The expression of bcl-2 protein occurs independently of and is
      inversely correlated with p53 mutations in advanced prostate cancer.

PMID- 8996360
TI  - Prostate cancer--research versus clinical patient management.

PMID- 8996361
TI  - Easy visualization of the membranous urethral stump in radical prostatectomy.
AB  - PURPOSE: Access to the urethral stump is sometimes difficult during radical
      retropublic prostatectomy. MATERIALS AND METHODS: A 20F Foley catheter with the 5
      ml. balloon inflated with 10 ml. in the bulbous urethra was used to elevate the
      urethral stump into the operative field. RESULTS: Easy access to the urethral
      stump was achieved in all patients, which assisted with accurate anastomosis.
      There was decreased leakage of urine and no anastomotic stricture. No urethral
      trauma or incontinence was attributable to the technique. CONCLUSIONS: This
      simple and safe technique allowed easy access to the urethral stump.

PMID- 8996362
TI  - Partial resection of symphysis: an aid in radical prostatectomy.
AB  - PURPOSE: Resection of a posterior symphyseal osteophyte during radical retropubic
      prostatectomy was evaluated. MATERIALS AND METHODS: The surgical technique is
      described. RESULTS: A favorable experience was noted in 10 patients with partial
      symphyseal resection. CONCLUSIONS: Partial symphyseal resection of an osteophyte
      protruding from the posterior symphysis can facilitate radical retropubic
      prostatectomy by improving visualization of the apex of the prostate.

PMID- 8996363
TI  - Diabetic cystopathy: relationship to autonomic neuropathy detected by sympathetic
      skin response.
AB  - PURPOSE: The possible relationship between bladder dysfunction and autonomic
      neuropathy was investigated in unselected diabetic patients. MATERIALS AND
      METHODS: Bladder function was examined by cystometry in 53 unselected diabetic
      patients and 10 healthy controls. Sympathetic skin response was recorded in 23 of
      53 patients and all control subjects to evaluate autonomic neuropathy associated
      with diabetes, and the results were compared to cystometric findings. RESULTS:
      Cystometrograms exhibited significant increases in bladder volume at first desire
      to void and maximal bladder capacity, and a decrease in detrusor contractility in
      diabetic patients compared to those in controls. In addition, mean residual urine
      was significantly larger in diabetic patients than in controls. Among the 53
      diabetic patients these bladder dysfunctions were also found in each subset of
      patients with no sign of retinopathy (33), no subjective urinary symptoms (32) or
      duration of diabetes less than 1 year (12). In 23 patients in whom sympathetic
      skin response was measured 12 without sympathetic skin responses had increased
      residual urine and decreased detrusor contraction pressure. The remaining 11
      patients with a lower amplitude of sympathetic skin response and more prolonged
      latency than controls had a significant decrease in detrusor contraction
      pressure. CONCLUSIONS: Bladder dysfunction, characterized by loss of sensation,
      increased capacity and decreased contractility, was the main observation of
      diabetic cystopathy regardless of the duration or severity of the disease. The
      association of bladder dysfunction and autonomic neuropathy detected by the
      sympathetic skin response might indicate that diabetic cystopathy is a
      manifestation of peripheral neuropathy induced by diabetes.

PMID- 8996364
TI  - Desensitization of bladder sensory fibers by intravesical capsaicin has long
      lasting clinical and urodynamic effects in patients with hyperactive or
      hypersensitive bladder dysfunction.
AB  - PURPOSE: Capsaicin was used to treat symptomatic patients with hyperactive or
      hypersensitive bladders. MATERIALS AND METHODS: Capsaicin solution (1 mM.) was
      instilled into the bladder of 16 patients with spinal hyperreflexia, bladder
      instability or hypersensibility. RESULTS: Frequency decreased in 14 patients and
      continence was achieved in 10 of 14 incontinent cases. Mean first desire to void
      and maximal cystometric capacity increased significantly. These effects lasted
      for 6 to 12 months and were renewed following repeat treatment. CONCLUSIONS:
      Bladder afferent desensitization with capsaicin is promising in patients with
      motor or sensory bladder dysfunction, although initial pungency might limit its
      use.

PMID- 8996365
TI  - Initiation of voiding in humans: the nature and temporal relationship of urethral
      sphincter responses.
AB  - PURPOSE: The nature and sequence of events during the initiation phase of human
      micturition are unclear. Disagreement concerning the urethral sphincter response
      to detrusor contraction may stem from the functional extension of periurethral
      striated muscle to the bladder neck in many but not all individuals, and the
      methods used during conventional cystometry, in which individuals are asked to
      forestall urination for as long as possible (urgency voiding). We reasoned that
      by instructing individuals to void despite the lack of urgency (volitional
      voiding), and by stratifying results by whether striated muscle influence
      extended to the bladder neck, response of the proximal urethra might be more
      readily determined. MATERIALS AND METHODS: Using a triple microtip transducer
      catheter and a triple lumen fluid-filled catheter, we investigated 44 consecutive
      men and women with a variety of urodynamic findings, including 12 whose
      evaluation was normal. RESULTS: Despite the diversity of urodynamic diagnoses,
      once data were stratified as described, results were striking and uniform. The
      smooth muscle component of the bladder neck region contracted during the
      initiation of voiding in all subjects. Despite antecedent relaxation of the
      striated muscle sphincter, voiding did not begin until bladder pressure equaled
      or exceeded bladder neck pressure. CONCLUSIONS: Proximal urethral pressure
      increases in the initial phase of human micturition. These findings may have
      significant physiological, diagnostic and therapeutic implications.

PMID- 8996366
TI  - Detrusor activity index: quantification of detrusor overactivity by ambulatory
      monitoring.
AB  - PURPOSE: Ambulatory urodynamic monitoring has been developed and evaluated during
      the last decade, and its appreciation is growing rapidly. We investigated the
      usefulness of this technique to quantify detrusor activity, and developed a
      parameter to quantify the grade of detrusor overactivity. MATERIALS AND METHODS:
      We investigated 167 female patients with lower urinary tract symptoms and 61
      asymptomatic volunteers. Detrusor behavior was classified according to the
      medical history findings and independently based on urodynamic investigation. The
      possible categories were termed overactive or not overactive. Subjects who were
      classified consistently formed the 2 reference groups, which were used in the
      statistical analysis of logistic regression. RESULTS: By logistic regression a
      scoring rule was developed. The individual score (detrusor activity index 0 to 1)
      is a measure of detrusor activity during the filling phase. At a cutoff point of
      0.41 the sensitivity equaled specificity of 85% in our patient and volunteer
      groups. CONCLUSIONS: The scoring rule can be applied clinically as a test to
      detect and quantify detrusor overactivity in patients with urinary incontinence.

PMID- 8996367
TI  - Voiding dysfunction following transurethral resection of the prostate: symptoms
      and urodynamic findings.
AB  - PURPOSE: Persistent voiding dysfunction following transurethral resection of the
      prostate is not uncommon. We determined the correlation, if any, between the
      subjective complaints in men with voiding dysfunction after transurethral
      resection of the prostate and the urodynamic findings. MATERIALS AND METHODS: A
      total of 50 consecutive men with voiding dysfunction following transurethral
      resection of the prostate was evaluated with the American Urological Association
      symptom index and multichannel urodynamics. Patients with urethral stricture,
      urinary retention or prostate cancer were excluded from the study. Urodynamic
      parameters assessed included detrusor instability, bladder capacity, sphincteric
      insufficiency using the Valsalva leak point pressure, voiding pressure-flow
      studies as determined by the Abrams-Griffiths nomogram (obstructed, unobstructed
      or equivocal) and post-void residual. RESULTS: Mean patient age was 71 years and
      mean interval from last transurethral resection of the prostate was 58 months
      (range 2 to 252). Mean total, obstructive and irritative symptom scores were
      16.3, 5.8 and 10.5, respectively. A total of 20 patients (40%) complained of
      incontinence (14 urge and 6 stress). According to the Abrams-Griffiths nomogram
      62% of the cases were unobstructed, 16% obstructed and 22% equivocal. Urodynamic
      abnormalities were demonstrated in 43 patients (86%), and included detrusor
      instability (54%), obstruction with or without detrusor instability (16%),
      sphincteric insufficiency (8%), detrusor hypocontractility (4%) and sensory
      urgency (4%). There was no difference in the total, irritative or obstructive
      scores among obstructed, unobstructed or equivocal cases. Similarly there was no
      difference in scores among patients with and without detrusor instability. Age,
      number of transurethral resections and interval since last transurethral
      resection were unrelated to pressure-flow results or detrusor instability. Post
      void residual was significantly greater in obstructed cases and bladder capacity
      was significantly less in those with detrusor instability. The cause of
      incontinence was demonstrated in 19 of 20 patients (95%): 4 (20%) had sphincteric
      insufficiency and 15 (75%) had detrusor instability. CONCLUSIONS: Symptoms are
      unreliable in predicting urodynamic findings with respect to obstruction and
      detrusor instability. There is a high incidence of detrusor instability in
      patients with voiding dysfunction after transurethral resection of the prostate.
      Urodynamic obstruction is a less likely occurrence.

PMID- 8996368
TI  - Urodynamic findings in the tethered spinal cord syndrome: does surgical release
      improve bladder function?
AB  - PURPOSE: We retrospectively reviewed 39 patients with a tethered spinal cord to
      evaluate whether surgical release positively influenced urological symptoms or
      urodynamic findings. MATERIALS AND METHODS: The patients were divided into 2
      groups: group 1-11 with occult spinal dysraphism and group 2-28 with secondary
      spinal cord tethering after previous closure of a myelomeningocele or resection
      of a lipomyelomeningocele. Diagnosis was confirmed in all cases by magnetic
      resonance imaging or spinal ultrasound. A comprehensive urodynamic evaluation was
      done immediately preoperatively and 2 to 21 months (mean 7) postoperatively.
      RESULTS: In group 1 the most common preoperative urodynamic finding was
      hyperreflexia, which improved or resolved after untethering in 62.5% of the
      patients. Four adults also reported improved bladder sensation or decreased
      urgency. In group 2 the most common urodynamic finding was impaired compliance,
      followed closely by detrusor hyperreflexia. Urodynamic patterns of detrusor
      hyperreflexia or compliance improved in only 30% of the patients, while 48% had
      worsened patterns. Only 14% of group 2 had improved symptoms of urinary control
      but 28% had improved lower extremity function. CONCLUSIONS: Urological symptoms
      and urodynamic patterns may be improved by early surgical intervention in
      patients with occult spinal dysraphism. However, untethering did not consistently
      benefit patients with secondary spinal cord tethering.

PMID- 8996369
TI  - Posterior sacral rhizotomy and intradural anterior sacral root stimulation for
      treatment of the spastic bladder in spinal cord injured patients.
AB  - PURPOSE: The efficacy of intradural sacral posterior rhizotomy combined with
      intradural sacral anterior root stimulation in the treatment of the neurogenic
      hyperreflexic bladder was evaluated. MATERIALS AND METHODS: We reviewed 10 spinal
      cord injured patients who underwent surgery between September 1990 and February
      1994. Bladder function was compared preoperatively and postoperatively.
      Intraoperative data on electrostimulation of the detrusor and striated muscles
      were analyzed. RESULTS: Stimulation of the anterior S3 and S4 roots was mostly
      used to empty the bladder (7 of 10 cases). Preoperative reflex incontinence
      disappeared in all patients postoperatively. Mean postoperative bladder capacity
      increases and mean postoperative post-void residual decreases were at least 340
      ml. (p < 0.01) and 140 ml. (p < 0.01), respectively. Preoperative vesicorenal
      reflux disappeared in 2 and improved in 3 cases after sacral deafferentation.
      Autonomic hyperreflexia, which was present preoperatively in 6 patients, never
      disappeared but significantly improved after deafferentation. No major
      complications were noted postoperatively. CONCLUSIONS: Intradural sacral
      posterior rhizotomy combined with intradural sacral anterior root stimulation is
      a valuable method to treat the hyperreflexic bladder with incontinence resistant
      to conservative therapy in spinal cord injured patients. Autonomic hyperreflexia
      was decreased but not suppressed by posterior sacral rhizotomy.

PMID- 8996370
TI  - Neurourology--the last frontier.

PMID- 8996371
TI  - Systemic infection resembling hemorrhagic fever with the renal syndrome caused by
      adenovirus type 11.

PMID- 8996372
TI  - A retroperitoneal bronchogenic cyst treated with laparoscopic surgery.

PMID- 8996373
TI  - Panurothelial condyloma acuminatum with development of squamous cell carcinoma of
      the bladder and renal pelvis.

PMID- 8996374
TI  - Psoriasis: association with 2 rare cutaneous urological malignancies.

PMID- 8996375
TI  - A rare complication after endoscopic resection of the prostate: osteitis pubis
      due to a prostate-symphysis fistula.

PMID- 8996376
TI  - Metastatic adenocarcinoma of the prostate to the orbit as a presenting symptom.

PMID- 8996377
TI  - Painful ejaculation due to seminal vesicle calculi.

PMID- 8996378
TI  - Re: Initial evaluation of the bladder tumor antigen test in superficial bladder
      cancer.

PMID- 8996379
TI  - Re: Editorial comment: should Stamey colposuspension be our primary surgery for
      stress incontinence?

PMID- 8996380
TI  - Re: Ameliorative effect of allopurinol on nonbacterial prostatitis: a parallel
      double-blind controlled study.

PMID- 8996381
TI  - Re: Transurethral microwave thermotherapy for nonbacterial prostatitis: a
      randomized double-blind sham controlled study using new prostatitis specific
      assessment questionnaires.

PMID- 8996383
TI  - Re: Radical prostatectomy with preservation of urinary continence.

PMID- 8996382
TI  - Re: Postoperative radiotherapy for stage pT3 carcinoma of the prostate: improved
      local control.

PMID- 8996384
TI  - Focal xanthogranulomatous pyelonephritis in a 12-year-old Alaskan native.

PMID- 8996385
TI  - Clear cell melanoma of the renal pelvis presenting as a primary tumor.

PMID- 8996386
TI  - The role of ureter in the creation of Mitrofanoff channels in children.
AB  - PURPOSE: Since 1980 numerous variations of the Mitrofanoff principle have been
      described. We report on 22 children in whom a ureteral Mitrofanoff channel was
      created. MATERIALS AND METHODS: Between 1986 and 1995 a ureteral Mitrofanoff
      channel was constructed as a catheterizable conduit in 22 children 2 to 15 years
      old (average age 6.5) with various abnormalities of the lower urinary tract,
      mainly exstrophy and neurogenic bladder. Indications included unavailability or
      unsuitability of the appendix, preference for appendix as a catheterizable
      colonic stoma for antegrade washouts or concomitant removal of a nonfunctioning
      kidney, leaving the ureter available for use. Surgical technique was based on the
      principles of appendicovesicostomy and in 9 cases the ureteral Mitrofanoff
      channel was reimplanted. RESULTS: Followup ranged from 1 to 72 months (average
      30.5). Complications included stenosis of the conduit that caused difficult
      catheterization in 3 patients, necessitating dilation or minor revision in 2 and
      complete replacement by appendix in 1. Urinary leakage from the Mitrofanoff
      channel in 5 patients was treated with polydimethylsiloxane injection or
      oxybutinin. In 1 patient the channel was reimplanted, since the catheter struck
      the bladder neck during catheterization and caused severe pain. CONCLUSIONS:
      Results of the ureteral Mitrofanoff channel seem somewhat less satisfactory than
      those of appendicovesicostomy but they remain acceptable and even comparable,
      strongly supporting its use in certain circumstances.

PMID- 8996387
TI  - Complications of intravesical oxybutynin chloride therapy in the pediatric
      myelomeningocele population.
AB  - PURPOSE: We report our experience with the intravesical administration of
      oxybutynin chloride with particular focus on the incidence and characterization
      of untoward effects and inconvenience of therapy. MATERIALS AND METHODS: From
      1990 to 1995, 23 children 5 to 11 years old with myelodysplasia were treated with
      intravesical oxybutynin chloride. Initial dose was 1.25 mg. in 5 cc sterile water
      instilled during routine catheterization 3 times daily, which was increased as
      tolerated and clinically indicated. Oral anticholinergic, antispasmodic and
      sympathomimetic medications were discontinued during therapy. We reviewed
      therapeutic indications, doses, frequency duration, reason for discontinuation
      and untoward effects. Patients/parents were surveyed for convenience of treatment
      as well as side effects and their timing with respect to drug administration and
      dose. RESULTS: In 15 patients (65%) treatment was discontinued and oral
      formulations were resumed or other therapy was required due to side effects,
      ineffectiveness or inconvenience. Seven patients had untoward effects, ranging
      from facial flushing and dizziness to agoraphobia and hyperactivity. Six patients
      discontinued therapy due to side effects after 1 day to 2 years (mode 1 month) at
      doses of 1.25 to 5 mg., including 5 who previously had side effects from oral
      oxybutynin chloride. Inconvenience of therapy was noted irrespective of the
      degree of independence of the child for performing intravesical therapy.
      CONCLUSIONS: Untoward effects and inconvenience are the most common reasons for
      discontinuing intravesical oxybutynin chloride therapy for neurogenic bladder
      dysfunction. Children who previously had side effects from oral oxybutynin
      chloride are more likely to have them during intravesical therapy.

PMID- 8996388
TI  - Posttraumatic posterior urethral strictures in children: a 20-year experience.
AB  - PURPOSE: We attempted to identify the particular features of strictures
      complicating pelvic fracture urethral injuries in children. MATERIALS AND
      METHODS: A total of 68 boys 3 to 15 years old who had sustained pelvic fracture
      urethral disruption underwent 78 urethroplasties performed by bulboprostatic
      anastomosis through the perineum in 42, transpubically in 23 and by 2-stage
      urethroscrotal inlay in 13. RESULTS: Perineal and transurethral urethroplasty was
      successful in 93 and 91% of cases respectively. There was a 54% failure rate
      after urethroscrotal inlay. CONCLUSIONS: Urethral strictures were most commonly
      associated with Malgaigne's fracture (35% of cases) and straddle fracture with or
      without diastasis of the sacroiliac joint (26%). Strictures were almost
      invariably inferior to the verumontanum with prostatic displacement in 44% of
      cases. Length of the strictured segment may be overestimated or underestimated on
      urethrography as a result of incomplete filling of the prostatic urethra or a
      urinoma cavity connected with the proximal segment, respectively. Perineal or
      transpubic bulboprostatic anastomosis is the best treatment for posttraumatic
      strictures, while internal urethrotomy should be avoided since it may compromise
      the chance of subsequent anastomotic urethroplasty. Repair of associated bladder
      neck incompetence may be deferred until the resumption of urethral voiding after
      urethroplasty, when incontinence can be documented.

PMID- 8996389
TI  - Water intoxication in a patient with the Prader-Willi syndrome treated with
      desmopressin for nocturnal enuresis.
AB  - PURPOSE: We report on a girl with the Prader-Willi syndrome who received
      desmopressin for nocturnal enuresis, and water intoxication developed after she
      ingested a large amount of fluid. MATERIALS AND METHODS: The patient received 10
      mg. desmopressin at bedtime for enuresis. She was hospitalized when a major motor
      seizure and coma (Glasgow coma scale 8) occurred after ingesting 48 ounces of
      fluid. Treatment included 3% saline, followed by 5% dextrose in water and sodium
      chloride given intravenously. RESULTS: Serum sodium increased to 128 mEq./l. and
      serum glucose remained normal. Computerized tomography and magnetic resonance
      imaging of the head were normal and revealed no evidence of cerebral pontine
      myelinosis. Patient consciousness returned to normal by day 5 after the seizure.
      CONCLUSIONS: In patients treated with desmopressin the risk of a seizure or
      altered level of consciousness can be minimized by not ingesting large quantities
      of fluid. We recommend that patients drink no more than 8 ounces of fluid on any
      evening that desmopressin is administered.

PMID- 8996390
TI  - Intracorporeal phenylephrine reduces thioridazine (Mellaril) induced priapism in
      a child.

PMID- 8996391
TI  - Congenital neoplasm of the clitoris.

PMID- 8996392
TI  - Ischiopagus twins: an outcome analysis of urological aspects of repair in 3 sets
      of twins.
AB  - PURPOSE: We assessed the urological components of ischiopagus twins and outcomes
      of surgical correction. MATERIALS AND METHODS: We performed a longitudinal study
      of 3 pairs of twins who presented to a single institution for repair and analyzed
      the outcomes of certain aspects of repair. RESULTS: Three pairs of twins joined
      from diaphragm to pelvis and facing each other in an embracing posture were
      separated in the last 10 years at a single institution. Each pair of twins had a
      similar constellation of shared organs, including abdominal wall, bony pelvis,
      liver, bowel, crossed ureters, bladder and genitalia. Followup ranges from 18
      months to 10 years. All children are independent and ambulatory with fully healed
      wounds. Of the 6 kidneys 5 are functioning well. Of the 4 children old enough to
      undergo continence evaluation all are fully continent and void spontaneously.
      CONCLUSIONS: Conjoined twins can be successfully separated with an effective
      outcome.

PMID- 8996393
TI  - Clinical evaluation of a rapid diagnostic screen (URISCREEN) for bacteriuria in
      children.
AB  - PURPOSE: We assessed clinical use of the URISCREEN test for detecting significant
      bacteriuria in children and compared it to standard quantitative culture.
      MATERIALS AND METHODS: URISCREEN detects catalase in urine samples, reflecting
      the presence of at least 50,000 colony-forming units per ml. or 10 somatic cell
      per high power field. Catheterized urine specimens from 200 consecutive children
      scheduled to undergo urodynamic evaluation were tested by URISCREEN and
      quantitative culture methods. Sensitivity, specificity, positive and negative
      predictive values, and accuracy were determined. RESULTS: Of these specimens
      there were 22 false-positive and 16 false-negative URISCREEN results. Sensitivity
      was 65.2%, specificity 85.7%, positive predictive value 57.7%, negative
      predictive value 89.2% and overall accuracy 81%. CONCLUSIONS: URISCREEN is a
      rapid screen for bacteriuria. However, the high false-negative rate limits
      clinical use in the pediatric urological patient for whom detecting infection is
      essential.

PMID- 8996394
TI  - m-Calpain activation/depletion is associated with androgen-induced reduction of
      protein kinase C and proliferation of male accessory sex organ smooth muscle
      cells.
AB  - PURPOSE: In the guinea pig seminal vesicle smooth muscle (SVM), androgen
      dependent proliferation and terminal differentiation appear to be coupled to
      protein kinase C (PKC). This is based on the observations that both the soluble
      (cytosolic) enzyme and the Triton X-100 solubilizable form of the particulate
      enzyme were reduced during proliferation but were androgen-resistant in the
      amitotic state of adults. The purpose of the present investigation was to
      determine if the reduction in PKC activity was linked to the translocation of the
      activated enzyme to acceptor sites in the Triton X-100 insoluble fraction of the
      cell or reflected enzyme depletion due to proteolysis by androgen-dependent
      activation of the u- and/or m-calpains. MATERIALS AND METHODS: SVM was harvested
      from treated animals, homogenized and separated into soluble and particulate
      components. The particulate material was further fractionated into Triton X-100
      soluble and insoluble fractions. PKC activity was determined in all fractions
      using radioactive ATP. Cultures of pure smooth muscle cells from both human
      prostate and SVM were also employed to assess the role of calpain in smooth
      muscle growth. RESULTS: During androgen-induced proliferation, instead of a
      translocation of PKC activity to the Triton X-100 insoluble particulate fraction
      of the cell, PKC activity in this fraction was significantly reduced. The m
      calpain was the only isoform detected in SVM. At the peak of androgen-induced DNA
      synthesis in pre-pubertal castrate animals, m-calpain decreased 45% whereas in
      proliferative resistant SVM of adult castrates the protease was not significantly
      affected by androgen treatment. In pure smooth muscle cultures from the SVM as
      well as human prostate glands calpeptin the cell permeable inhibitor of calpains
      produced a concentration-dependent inhibition (IC50 approximately equal to 35
      microM) of cellular proliferation. CONCLUSIONS: Given that biochemical assays of
      calpain quantify the residual proenzyme and that upon activation calpain is
      rapidly degraded, our findings indicate that m-calpain activation occurs in
      association with androgen-induced degradation of PKC and SMC proliferation. Thus
      in vitro inhibition of m-calpain activation is antiproliferative. The relative
      resistance of m-calpain in adult SVM may be an important component of the
      terminal differentiation process in normal smooth muscle.

PMID- 8996395
TI  - Stress-induced bladder mast cell activation: implications for interstitial
      cystitis.
AB  - PURPOSE: To investigate whether acute psychological stress may activate bladder
      mast cells which appear to play a significant role in the pathophysiology of
      interstitial cystitis, a syndrome that occurs primarily in females and is
      characterized by urinary urgency, frequency and suprapubic pain, all of which
      often worsen with stress. MATERIALS AND METHODS: Non-traumatic immobilization
      stress was used as a model of acute emotional stress by placing a rat in a
      plexiglass immobilizer, after first bringing each rat in the laboratory daily for
      4 days to reduce the stress of handling. The rat was then anesthetized,
      decapitated and the bladder removed and fixed for light and electron microscopy.
      RESULTS: This type of stress resulted in activation of over 70% of bladder mast
      cells within 30 minutes, as evidenced by light and electron microscopy.
      Pretreatment of the animals with intraperitoneal administration of polyclonal
      antiserum to corticotropin releasing hormone had no effect on bladder mast cell
      activation and no nerve fibers positive for this hormone were identified in the
      bladder. Stress-induced bladder mast cell activation was, however, substantially
      reduced in animals treated neonatally with capsaicin suggesting that sensory
      neuropeptides, such as substance P, of which increased positive nerve fibers have
      been localized close to bladder mast cells, are involved in this response.
      CONCLUSIONS: This is the first time that psychological stress is shown to
      activate bladder mast cells, apparently via the action of at least some sensory
      neuropeptides. These findings have implications for the pathophysiology and
      possible therapy of interstitial cystitis.

PMID- 8996396
TI  - Glutathione S-transferase PI (GST-pi) class expression by immunohistochemistry in
      benign and malignant prostate tissue.
AB  - PURPOSE: Glutathione S-transferase (GST) enzymes may prevent carcinogenesis
      through inactivation of reactive electrophiles by conjugation to reduced
      glutathione. Recently, it was reported that most prostate cancers fail to express
      GST-pi despite an abundant presence in benign prostate tissue, suggesting a
      common genetic alteration. To define its presence in prostate tissue, we
      evaluated GST-pi expression in a variety of prostate tissues. MATERIALS AND
      METHODS: Immunostaining with anti-GST-pi antibody was performed on 69 benign
      prostates, 44 malignant prostates, 12 incidental prostate carcinomas and 17
      prostatic intraepithelial neoplasia (PIN) specimens. Specimens were evaluated for
      the presence and percent of GST-pi. Within benign tissue, GST-pi immunostaining
      was distinguished between basal cells and secretory acinar epithelium. RESULTS:
      In benign epithelium, the basal cells demonstrated intense staining in all cases.
      The mean percent staining among the basal cells was 67% (R 40-90%). The acinar
      epithelium stained weakly positive in 94% (65/69) of specimens, however the mean
      percent staining was only 5% (R 0-25%). GST-pi was detected in only 3.5% (2/56)
      of the prostate cancers. No incidental prostate cancers and only one (6%) high
      grade PIN stained positive. CONCLUSIONS: Our study confirms the absence of GST-pi
      expression in prostate cancer and high grade PIN. Furthermore, GST-pi expression
      correlates well with the basal cell phenotype, but not with benign epithelial
      cells. The lack of staining among prostate cancer cells may reflect the absence
      of a basal cell layer, suggesting that GST-pi is involved more in epithelial
      differentiation and questioning its role in the malignant transformation of
      prostatic acinar cells.

PMID- 8996397
TI  - Time-dependent remodeling of the bladder wall in growing rabbits after partial
      outlet obstruction.
AB  - PURPOSE: We asked whether a urethral constriction gradually developed during
      growth would give rise to a structural remodeling of the bladder wall distinct
      from that of the mature rabbits in terms of cellular response. MATERIALS AND
      METHODS: We examined the serosa and detrusor muscle in immature rabbits whose
      urethra was obstructed at 30 days postnatal and studied 7 to 30 days after
      partial outlet obstruction. Morphometry, bromo-deoxyuridine (BrdU) incorporation,
      Western blotting and immunocytochemical staining with a panel of monoclonal
      antibodies specific to selected cytoskeletal, cytocontractile and membrane
      related proteins unique to non-muscle and smooth muscle cells (SMC) were used to
      analyze the effects of obstruction on the differentiation pattern. RESULTS: In
      comparison with results in adult obstructed bladders, we have found that in
      growing rabbits: (1) the cell conversion from fibroblasts to SMC, occurring
      within the 'extrinsic' region of serosal thickening, takes place earlier; (2)
      newly formed SMC are localized exclusively to the thickened serosa, and can group
      in bundles depending on the density of the regional innervation; (3) the peak
      level of BrdU incorporation is more elevated than in the adult bladder wall; and
      (4) change in the phenotypic profile of SMC of detrusor muscle is delayed.
      CONCLUSION: These data indicate that the basic features of structural remodeling
      in the two models are similar, though partial outlet obstruction produced in
      growing animals accelerates the fibroblast conversion to SMC and their spatial,
      differentiation-specific arrangement in the serosa. The late phenotypic changes
      in obstructed detrusor muscle correlate with the decline of the DNA synthesis
      level after an initial burst and strongly suggest that newly formed SMC in the
      serosa do not derive from pre-existing SMC.

PMID- 8996398
TI  - Angiogenesis inhibitor TNP-470 suppresses tumorigenesis in rat urinary bladder.
AB  - PURPOSE: The efficacy of the anti-angiogenic factor TNP-470, an analogue of
      fumagillin, in controlling the development of bladder tumors was investigated.
      MATERIALS AND METHODS: The anti-angiogenic activity of TNP-470 was evaluated in
      vitro by its capacity to suppress the growth and migration of bovine capillary
      endothelial cells. To investigate its effect in vivo on the development of
      tumors, we instilled 0.5 microgram of TNP-470 dissolved in rat urine into
      heterotopically transplanted rat urinary bladders in which carcinogenesis had
      been initiated by N-methyl-N-nitrosourea. RESULTS: In vitro, TNP-470 selectively
      inhibited the growth and migration of endothelial cells. Instillation of TNP-470
      shortly after treatment with carcinogen reduced the tumor incidence significantly
      (p < 0.05) as compared with that in control animals receiving urine only.
      CONCLUSIONS: TNP-470 suppresses the development of bladder tumors when the
      treatment is started at an early stage of neoplasia. It may be useful in
      preventing recurrences or new growth of bladder tumors.

PMID- 8996399
TI  - Human anti-IgE monoclonal antibody blocks passive sensitization of human and
      rhesus monkey bladder.
AB  - IgE antibodies may play an important role in noninfectious urinary inflammation,
      including interstitial cystitis (IC). In this study, urinary bladder strips were
      passively sensitized for 20 hours with serum from a ragweed-sensitive patient in
      the absence or presence of an anti-human IgE monoclonal antibody (MaE11) at 0, 1
      , or 5-fold IgE concentration. The urinary bladder strips then were suspended in
      a superfusion apparatus for measurement of contraction and histamine release in
      response to antigen E (AgE) challenge. Non-sensitized tissues did not react to
      AgE challenge, whereas AgE challenge of passively-sensitized tissues resulted in
      time-dependent bladder contraction and histamine release. MaE11 abolished AgE
      induced contraction and histamine release in a concentration-dependent manner.
      The safety of MaE11 was confirmed by its failure to contract or release histamine
      from passively-sensitized bladder tissues. The results of this study suggest that
      MaE11 may have immunotherapeutic benefit for amelioration of IgE-mediated
      diseases of the urinary system.

PMID- 8996400
TI  - New fimbrial adhesins of Serratia marcescens isolated from urinary tract
      infections: description and properties.
AB  - Fimbriation, hemagglutination and adherence properties were studied in two
      strains of S. marcescens (ATCC 43820 and 43821) isolated from the urine of two
      hospitalized patients in two different hospitals. Studies were performed using
      electron microscopy (EM), fimbrial purification, recombinant DNA and
      hemagglutination techniques, hydrophobicity and tests of adherence to
      uroepithelial cells, catheters and glass. In EM, fimbriae of these two strains
      showed an inner channel and were 11 nm. thick and 0.76-1.08 microns long.
      Original strains and the clone GH42-pSF192 (recombinant DNA prepared using E.
      coli GH42 as recipient and the cosmid SuperCos 1 as a vector) versus negative
      control (E. coli GH42-SuperCos 1) showed mannose-resistant hemagglutination of
      tanned erythrocytes and yeast, high hydrophobicity (55.4 and 49.6% at 37C versus
      22.8%) and high adherence to borosilicate glass (313,000 and 168,000 CFU/cm.2
      versus 17,000 CFU/cm.2), catheters (4.7 x 10(6) and 1.0 x 10(6) CFU/cm.2 versus
      3.9 x 10(4) CFU/cm.2) and uroepithelial cells (adherence indexes of 3.82 and 3.29
      versus 1.25). The properties of the fimbriae studied were different from those
      previously described in the genus Serratia, and they were designated as MR/T.

PMID- 8996401
TI  - Induction of tubulogenesis of microvascular endothelial cells by basic fibroblast
      growth factor from human SN12C renal cancer cells.
AB  - PURPOSE: To investigate the role of basic fibroblast growth factor (b-FGF) in
      angiogenesis in renal cell carcinoma. MATERIALS AND METHODS: We examined b-FGF
      expression in 25 patients with renal cell carcinoma (RCC) by reverse
      transcriptase polymerase chain reaction (RT-PCR). We measured the tube formation
      by human omental microvascular endothelial (HOME) cells induced by b-FGF in a
      three-dimensional collagen gel in the absence or presence of SN12C human renal
      cancer cells by means of computer-image analysis. RESULTS: RT-PCR analysis
      detected b-FGF m-RNA in 20 (80%) of 25 patients with RCC. The tube formation of
      HOME cells was increased in the presence of SN12C cells overexpressing b-FGF
      mRNA, induced by exogenous b-FGF in a dose dependent manner and completely
      inhibited by anti-b-FGF antibody. CONCLUSIONS: Basic-FGF may develop tumor
      angiogenesis by inducing microvessel tubulogenesis in patients with RCC.

PMID- 8996402
TI  - A telemetric multichannel computer-based system for monitoring urodynamic
      parameters in awake rhesus monkeys.
AB  - For comprehensive telemetric monitoring of bladder function in monkeys,
      transducers were implanted in the bladder wall and abdominal cavity. The EMG lead
      was buried in the external sphincter. All wires terminated in a subcutaneous
      transmitter. Conventional urodynamics were performed for comparison. Excellent
      reproducibility with conventional urodynamics was found. Implantation caused
      detrusor instability, which subsided in 6 to 8 weeks. Real-time computer-based
      multichannel telemetric studies of voiding are feasible and reliable. Telemetric
      studies monitor for long periods without stress or anesthesia and provide an
      excellent model for lower urinary tract studies.

PMID- 8996403
TI  - Renal cryotherapy in a sheep model; a feasibility study.
AB  - PURPOSE: This study was designed to evaluate the safety and efficacy of renal
      cryotherapy as a possible treatment of renal malignancy with preservation of
      renal parenchyma. MATERIALS AND METHODS: Ten Merino sheep were anaesthetised and
      the right kidney was exposed through a retro-peritoneal approach. A 5 mm.
      cryotherapy probe (LCS 3000 Cryotec UK) was inserted into the lower pole of the
      kidney and freezing was undertaken to form an iceball 5 cm. in diameter. RESULTS:
      There was no mortality and no complications were observed. A transient rise in
      creatinine was observed post-operatively. The sheep were euthenased at 4 weeks
      and at necropsy macroscopic examination revealed a contracted, fibrotic wedge
      shaped lesion of 3 cm in diameter. Histological examination of the "cryolesion"
      revealed a central area of coagulative necrosis and a 5 mm rim of partial
      necrosis with preservation of renal tubules. CONCLUSION: We conclude that renal
      cryotherapy is safe and can achieve effective renal necrosis in the sheep model.

PMID- 8996404
TI  - Prostatic intraepithelial neoplasia occurs spontaneously in the canine prostate.
AB  - PURPOSE: Prostatic intraepithelial neoplasia (PIN) is the most likely precursor
      of human prostate cancer. Although the dog is the only non-human species in which
      spontaneous prostate cancer occurs frequently, the prevalence of PIN in the
      canine prostate is unknown. A naturally occurring animal model of PIN has not
      been described. MATERIALS AND METHODS: To determine if high grade PIN occurs
      spontaneously in the canine prostate, we evaluated totally embedded prostates
      from 35 outbred dogs that had no clinical evidence of prostatic disease.
      Prostates from three groups of dogs were analyzed: (1) 11 sexually intact dogs 7
      17 years old (elderly sexually intact); (2) 13 sexually intact dogs 1-4 years old
      (young sexually intact); and (3) 11 dogs 7-17 years old that had been castrated
      (elderly castrated). The prevalence of PIN was determined by systematic
      evaluation of hematoxylin/eosin and high molecular weight keratin 34 beta-E12
      stained tissue sections from formalin-fixed, paraffin embedded prostates that had
      been serially sectioned at 4 mm intervals. RESULTS: Canine high grade PIN showed
      cytologic features identical to the human counterpart, including cell crowding,
      loss of polarity, and nuclear and nucleolar enlargement. Foci of high grade PIN
      were present in the prostates of 6 of 11 (55%) elderly, sexually intact dogs but
      only 1 of 13 (8%) dogs less than 4 years old. Foci of high grade PIN were
      detected in 1 of 11 (9%) elderly castrated dogs. In elderly, sexually intact dogs
      with PIN, foci of high grade PIN were present in 13 of 83 (16%) tissue sections
      evaluated; one of these dogs had focal adenocarcinoma in addition to PIN.
      CONCLUSIONS: These results indicate that high grade PIN is frequently present in
      the prostate of elderly, sexually intact dogs. The prevalence of canine PIN, like
      human PIN, is apparently influenced by age and testicular androgens. The canine
      prostate may serve as a useful model to determine the factors that regulate the
      apparent progression from benign epithelium to PIN and invasive carcinoma.

PMID- 8996405
TI  - Evidence for the presence of regional differences in the subtype specificity of
      muscarinic receptors in rabbit lower urinary tract.
AB  - To elucidate the subtype specificity of muscarinic cholinergic receptors in
      mediating contractile responses in the lower urinary tract, we investigated
      contractile and biochemical properties of muscarinic receptors in bladder dome,
      bladder base and urethra of the rabbit. Isometric contractile response curves to
      increasing concentrations of carbachol were constructed in the absence and
      presence of various concentrations of subtype selective muscarinic antagonists.
      Bladder dome, bladder base, and urethra demonstrate different characteristics in
      terms of efficacy and potency with respect to carbachol-induced contractile
      responses. Emax values are significantly larger and ED50 values are significantly
      smaller in bladder dome and bladder base than in urethra. Calculation of the pA2
      values, the negative logarithm of the antagonist affinity constant (KB), for a
      series of muscarinic antagonists, i.e., atropine (nonselective), pirenzepine (M1
      selective), methoctramine (M2 selective), and 4-DAMP (M1/M3 selective) indicate
      that the carbachol-induced contractile response in bladder dome and bladder base
      is mediated through the M3 receptor subtype whereas the carbachol-induced
      contractile response in urethra is probably mediated through the M1 and/or M3 and
      possibly M2 subtypes. Muscarinic cholinergic antagonists inhibit [3H]quinulidinyl
      benzilate binding to bladder dome, bladder base and urethra with the following
      rank order of affinities: atropine > 4-DAMP > methoctramine > pirenzepine. The
      binding data indicate the predominance of the M2 receptor subtype in all three
      regions.

PMID- 8996406
TI  - Acidosis impairs rabbit trabecular smooth muscle contractility.
AB  - PURPOSE: The aim of our study was to define the effects of acidosis on the
      contractility of trabecular smooth muscle. METHODS: Rabbit corpus cavernosal
      strips were mounted in organ chambers to measure isometric tension. Additionally,
      intracellular free Ca2+ concentration ([Ca2+]i) and tension were measured
      simultaneously utilising the intracellular fluorescent dye, FURA-2, and isometric
      tension recordings. RESULTS: Contraction of corpus cavernosum smooth muscle
      following transmural electrical stimulation (TES) of constrictor nerves or
      exposure to norepinephrine was depressed under acidic (pH 6.9) vs. control (pH
      7.4) conditions. Twenty mM K(+)-induced contractions were also inhibited by
      acidosis, however 40, 80, and 120 mM K+ contractions were unaffected. Relaxation
      responses to acetylcholine and electrical stimulation, in phenylephrine
      contracted tissues, were unaffected by acidosis. Tissues contracted with 20 mM K+
      under control conditions, relaxed approximately 50% when exposed to an acidic
      environment. This relaxation was blocked by exposing the tissue to 80 mM K+.
      Acidic conditions inhibited basal tone and [Ca2+]i as well as normal increases in
      both intracellular free Ca2+ and tension upon exposure to 20 mM K+, while 80 mM
      K(+)-induced increases in Ca2+ and tension were comparable under both neutral and
      acidic conditions. CONCLUSION: Acidosis impairs trabecular smooth muscle
      contractility. This alteration is probably secondary to the interference of [H+]
      with the intra and extracellular mechanisms that regulate homeostasis of [Ca2+]i.
      Since acidosis is an early complication of ischemic priapism, we propose that the
      reduced contractility of trabecular smooth muscle may be a significant factor in
      the perpetuation of the ischemic state.

PMID- 8996407
TI  - The correlation of membranous glycoprotein-gp-170, cytoplasmic glutathione and
      glucose-6-phosphate dehydrogenase levels with multidrug resistance in
      transitional cell carcinoma cell lines of the urinary tract.
AB  - The expression of membranous glycoprotein gp-170, cytoplasmic glutathione (GSH)
      and energy-related glucose-6-phosphate dehydrogenase (G-6-PD) in cultured normal
      urothelial cells and transitional cell carcinoma (TCC) cell lines was analyzed by
      flow cytometric and enzymatic methods. The chemosensitivity of these tumor cells
      to four major types of anticancer drugs, including cisplatin, thiotepa,
      methotrexate, 5-fluorouracil, adriamycin and vinblastine, was correlated with
      biological activities in TCC cell lines. The TCC cell lines displayed a general
      sensitivity to anticancer drugs with a low incidence of highly resistant cell
      lines (23%). The expression of multidrug resistance was not related to cellular
      differentiation or invasiveness of cancer cells. Only 24% of TCC cell lines had
      an elevated expression of gp-170, but their expression was not related to drug
      resistance. Increased cytoplasmic GSH and G-6-PD was observed in over 90 per cent
      of TCC cell lines, but no correlation with drug resistance and cellular
      differentiation was observed. The biological activities of GSH and G-6-PD were
      not related to the drug resistance of TCC. The low expression rate of gp-170 in
      TCC cells indicates that other mechanisms should be involved in the development
      of MDR in TCC cells.

PMID- 8996408
TI  - Calcium regulation of urinary bladder function.
AB  - PURPOSE: To investigate the effect of independently inhibiting calcium influx
      from extracellular sources and calcium release from intracellular stores on the
      ability of the urinary bladder to generate pressure and empty. MATERIALS AND
      METHODS: Rabbit bladders were mounted in an in vitro whole organ bath and filled
      with 15 ml. saline. Each bladder was incubated separately in Tyrode's solution,
      with diltiazem (10 microM), to block extracellular calcium influx, or with
      thapsigargin (40 microM) and ryanodine (80 microM), to block the uptake and
      release of calcium from the sarcoplasmic reticulum. The bladder was then
      stimulated isometrically with field stimulation (32 Hz), and to empty with field
      stimulation and with bethanechol (250 microM), independently. During stimulation,
      transmural pressure and volume emptied were measured. From these, flow rate,
      power, and external mechanical work were calculated. RESULTS: In the presence of
      diltiazem, the time to maximal pressure decreased while the rate of pressure
      generation increased. This results from increased participation of intracellular
      calcium release, which occurs rapidly and near the smooth muscle filaments,
      decreasing the diffusion time. In the presence of thapsigargin and ryanodine the
      maximal rate of pressure generation was decreased, due to the increased diffusion
      time required for calcium to move to the muscle filaments from extracellular
      sites. CONCLUSIONS: The current study demonstrates that bladder pressure
      generation and emptying are dependent upon both an influx of calcium through L
      type calcium channels (inhibited by diltiazem) and the stimulated release of
      calcium from the SR (inhibited by thapsigargin and ryanodine).

PMID- 8996409
TI  - The influence of temocapril, an angiotensin converting enzyme inhibitor, on the
      cyclosporine-induced nephrotoxicity.
AB  - PURPOSE: We examined the effect of temocapril (Tem), an angiotensin converting
      enzyme inhibitor (ACEI), on the cyclosporine-induced nephrotoxicity (CsA-NT) in
      rats. MATERIALS AND METHODS: Male Wistar rats were used. Group 1 (G1) received a
      medium (i.e. olive oil) only, group 2 (G2) received CsA (30 mg./kg./d) only,
      group 3 (G3) received both CsA (30 mg./kg./d) and Tem (80 micrograms./kg./d), and
      group 4 (G4) received Tem (80 micrograms./kg./d) only. Each group consisted of 5
      animals. Drugs were given orally for fourteen days. Then, renal cortical blood
      flow (RCBF) and concentrations of serum creatinine (S-Cr), serum potassium (S-K),
      whole blood CsA (WB-CsA), serum aldosterone (Ald), and plasma renin activity
      (PRA) were measured. The creatinine clearance (CCr) was also calculated. Kidneys
      were processed to the light microscopic examination with Bowie stain, and the
      size of the renin granules (S-RGs) was estimated by an image analysis system.
      RESULTS: G2 showed a decrease of RCBF (p < 0.01), an increase of S-Cr (p < 0.01),
      a decrease of CCr (p < 0.01), an increase of S-K (p < 0.05), and an increase of S
      RGs (p < 0.01). Compared with G2, G3 showed significant improvement in RCBF (p <
      0.01) and S-Cr (p < 0.05), but still showed significant impairments in all
      indices (p < 0.01 or p < 0.05, vs control). G4 showed no remarkable changes
      comparing with G1, except a significant (p < 0.01, vs. control) increase of S-K.
      G3 showed additional effect on the increase of S-K (p < 0.01, vs. control and
      G2). Tem showed no significant influence on the WB-CsA level. The serum Ald and
      PRA levels were not significantly changed by these drugs. CONCLUSIONS: These data
      are compatible with the hypothesis that the vasoconstriction of the afferent
      arterioles (AAs) is a principal mechanism of CsA-NT. The increase of RGs may be
      the result of both increased production and inhibited secretion of renin.

PMID- 8996410
TI  - A good turn for Africa, please.

PMID- 8996411
TI  - "Glitazones", a prospect for non-insulin-dependent diabetes.

PMID- 8996412
TI  - Is death inevitable with multiresistant TB plus HIV infection?

PMID- 8996413
TI  - More resources, better survival?

PMID- 8996414
TI  - Detection of iron overload.

PMID- 8996416
TI  - Understanding acute leukaemias.

PMID- 8996415
TI  - Fields of controversy.

PMID- 8996417
TI  - Difference in countries' use of resources and clinical outcome for patients with
      cardiogenic shock after myocardial infarction: results from the GUSTO trial.
AB  - BACKGROUND: Use of aggressive and invasive interventions is more common in the
      USA than in other countries. We have compared use of resources for patients with
      cardiogenic shock after myocardial infarction in the USA and in other countries,
      and assessed the association between use of resources and clinical outcomes.
      METHODS: We analysed data for patients with cardiogenic shock after myocardial
      infarction who were enrolled in the GUSTO-I trial (1891 treated in the USA, 1081
      treated in other countries). Patients were randomly assigned combinations of
      streptokinase, heparin, and accelerated tissue-plasminogen activator (t-PA), then
      decisions about further interventions were left to the discretion of the
      attending physician. The interventions included in our analysis were: pulmonary
      artery catheterisation, cardiac catheterisation, intravenous inotropic agents,
      ventilatory support, intra-aortic balloon counterpulsation (IABP), percutaneous
      transluminal coronary angioplasty (PTCA), and coronary bypass graft surgery
      (CABG). The primary outcome measure was death from any cause at 30 days of follow
      up. FINDINGS: Patients who were treated in the USA were significantly younger
      than those treated elsewhere (median 68 [IQR 59-75] vs 70 [62-76], p < 0.001), a
      smaller proportion had anterior infarction (49 vs 53%, p < 0.001), and they had a
      shorter time to treatment (mean 3.1 vs 3.3 h, p < 0.001). Aggressive diagnostic
      and therapeutic procedures were used more commonly in the USA than in the other
      countries: cardiac catheterisation (58 vs 23%); IABP (35 vs 7%); right-heart
      catheterisation (57 vs 22%); and ventilatory support (54 vs 38%). 483 (26%) of
      the patients treated in the USA underwent PTCA, compared with 82 (8%) patients in
      other countries. Patients who underwent revascularisation had better survival in
      all countries. Adjusted 30-day mortality was significantly lower among patients
      treated in the USA than among those treated elsewhere (50 vs 66%, p < 0.001). The
      difference in mortality remained at 1 year-56% of patients treated in the USA
      died versus 70% of patients treated elsewhere (hazard ratio 0.69 [95% CI 0.63
      0.75], p < 0.001). INTERPRETATION: 30-day and 1-year mortality was significantly
      lower among patients treated in the USA than among those treated in other
      countries. This difference in mortality may be due to the greater use of invasive
      diagnostic and therapeutic interventions in the USA.

PMID- 8996418
TI  - Progression of ischaemic stroke and excitotoxic aminoacids.
AB  - BACKGROUND: Mechanisms involved in progression of stroke are little understood.
      Studies in animals have shown an association between neuronal death mediated by
      excitatory aminoacids and deterioration in focal cerebral ischaemia. We looked
      for an association between concentrations of glutamate and glycine in plasma and
      cerebrospinal fluid (CSF) and early progression in a prospective study of 128
      patients with acute ischaemic stroke. METHODS: Of 556 consecutive admissions to
      our emergency unit, 128 eligible patients with ischaemic stroke were included in
      our study. Blood and CSF samples were taken within the first 24 h from stroke
      onset when cerebral oedema had been excluded on a previous cranial computed
      tomography. Ischaemic stroke was judged to be in progression if the Canadian
      stroke scale score (1.5 = maximum neurological deficit, 10 = no deficit) fell by
      1 or more points during the first 48 h after inclusion. Glutamate and glycine
      concentrations in plasma and CSF were measured by high-performance liquid
      chromatography. The effect of plasma and CSF glutamate concentrations on
      progression was analysed by logistic regression. FINDINGS: 43 (33.6%) patients
      had progressing ischaemic stroke. Concentrations of glutamate and glycine in
      plasma and CSF were higher in patients with progressing stroke than in those with
      stable cerebral infarcts (p < 0.0001). There was a significant linear correlation
      between CSF and plasma concentrations of glutamate (r = 0.79, p < 0.001). The
      positive predictive value of a plasma glutamate concentration of more than 200
      mumol/L for progression of ischaemic stroke was 97% (95% CI 85-100). Glutamate
      concentrations of more than 200 mumol/L in plasma and of more than 8.2 mumol/L in
      CSF were independently and significantly associated with progression of
      neurological deficit (26.1 [6.9-98.6] and 40.9 [7.6-220], respectively).
      INTERPRETATION: Early neurological progression of acute ischaemic stroke is
      associated with high concentrations of glutamate in blood and CSF. Measurement of
      plasma glutamate may be useful for the early detection of those patients with
      acute stroke who will deteriorate during 48 h after onset.

PMID- 8996419
TI  - Population-based study of risk of venous thromboembolism associated with various
      oral contraceptives.
AB  - BACKGROUND: Four studies published since December, 1995, reported that the
      incidence of venous thromboembolism (VTE) was higher in women who used oral
      contraceptives (OCs) containing the third-generation progestagens gestodene or
      desogestrel than in users of OCs containing second-generation progestagens.
      However, confounding and bias in the design of these studies may have affected
      the findings. The aim of our study was to re-examine the association between risk
      of VTE and OC use with a different study design and analysis to avoid some of the
      bias and confounding of the earlier studies. METHODS: We used computer records of
      patients from 143 general practices in the UK. The study was based on the medical
      records of about 540,000 women born between 1941 and 1981. All women who had a
      recorded diagnosis of deep-vein thrombosis, venous thrombosis not otherwise
      specified, or pulmonary embolus during the study period, and who had been treated
      with an anticoagulant were identified as potential cases of VTE. We did a cohort
      analysis to estimate and compare incidence of VTE in users of the main OC
      preparations, and a nested case-control study to calculate the odds ratios of VTE
      associated with use of different types of OC, after adjustment for potential
      confounding factors. In the case-control study, we matched cases to controls by
      exact year of birth, practice, and current use of OCs. We used a multiple
      logistic regression model that included body-mass index, number of cycles, change
      in type of OC prescribed within 3 months of the event, previous pregnancy, and
      concurrent disease. FINDINGS: 85 women met the inclusion criteria for VTE, two of
      whom were users of progestagen-only OCs. Of the 83 cases of VTE associated with
      use of combined OCs, 43 were recorded as deep-vein thrombosis, 35 as pulmonary
      thrombosis, and five as venous thrombosis not otherwise specified. The crude rate
      of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users
      of second-generation OCs, and 4.96 in users of third-generation preparations.
      After adjustment for age, the rate ratio of VTE in users of third-generation
      relative to second-generation OCs was 1.68 (95% CI 1.04-2.75). Logistic
      regression showed no significant difference in the risk of VTE between users of
      third-generation and second-generation OCs. Among users of third-generation
      progestagens, the risk of VTE was higher in users of desogestrel with 20 g
      ethinyloestradiol than in users of gestodene or desogestrel with 30 g
      ethinyloestradiol. With all second-generation OCs as the reference, the odds
      ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol
      and 1.18 (0.66-2.17) for the other third-generation progestagens. INTERPRETATION:
      The previously reported increase in odds ratio associated with third-generation
      OCs when compared with second-generation products is likely to have been the
      result of residual confounding by age. The increased odds ratio associated with
      products containing 20 micrograms ethinyloestradiol and desogestrel compared with
      the 30 micrograms product is biologically implausible, and is likely to be the
      result of preferential prescribing and, thus, confounding.

PMID- 8996420
TI  - Does non-dysenteric intestinal amoebiasis exist?
AB  - BACKGROUND: Chronic abdominal pain and frequent bowel disturbance are common
      symptoms experienced by more than 15% of apparently healthy people. In areas
      endemic for Entamoeba histolytica infection, these symptoms are often diagnosed
      as non-dysenteric intestinal amoebiasis even though no causal relation between
      such symptoms and E histolytica has been established and clinical presentation of
      non-dysenteric intestinal amoebiasis and irritable bowel syndrome (IBS) is not
      distinct. This study was done to assess the clinical significance of E
      histolytica infection in causation of such symptoms. METHODS: Patients with
      symptoms suggestive of non-dysenteric intestinal amoebiasis were recruited from a
      survey to assess the prevalence of abdominal symptoms in the general population
      (group A; n = 78) and from medical outpatient clinics (group B; n = 66).
      Participants who had symptoms as well as symptom-free controls (group C; n = 100)
      were clinically examined and underwent stool examination, amoebic serology,
      colonoscopic examination, histopathological examination of colonoscopic biopsy
      samples, and a trial of antiamoebic therapy (only for participants with symptoms)
      with metronidazole and mebendazole. FINDINGS: There were no significant
      differences between the 144 patients with symptoms and the 100 symptom-free
      controls in the proportion with E histolytica in stools (26 [18%] vs 18 [18%]),
      serological evidence of E histolytica infection (61 [42%] vs 41 [41%]),
      colonoscopic abnormalities (five of 66 vs one of 33), or histopathological
      abnormalities (36 [49%] of 73 vs ten [30%] of 33). Cyst-positive and cyst
      negative individuals showed no significant difference in serological evidence of
      E histolytic infection, histological abnormalities, or response to therapeutic
      trial with metronidazole. A diagnosis of IBS was suggested on the basis of
      consensus criteria and Kruis diagnostic index in 127 of 144 patients with
      symptoms. The diagnosis of non-dysenteric intestinal amoebiasis could be made in
      only one patient, who had relapse of symptoms within 6 weeks of antiamoebic
      therapy and therefore the relapse did not meet criteria for the diagnosis of non
      dysenteric intestinal amoebiasis. More than 60% of cyst-positive as well as cyst
      negative patients with symptoms showed either complete or partial response to
      treatment strategy for IBS. INTERPRETATION: Chronic bowel symptoms, such as pain
      in abdomen and frequent bowel disturbance, have no association with either past
      or present infection with E histolytica. Most patients with such symptoms are
      likely to have IBS. The clinical entity of non-dysenteric intestinal amoebiasis,
      if it exists, must be extremely rare.

PMID- 8996421
TI  - Fatal encephalitis due to novel paramyxovirus transmitted from horses.
AB  - BACKGROUND: In September, 1994, an outbreak of severe respiratory disease
      affected 18 horses, their trainer, and a stablehand in Queensland, Australia.
      Fourteen horses and one human being died. A novel virus was isolated from those
      affected and named equine morbillivirus (EMV). We report a case of encephalitis
      caused by this virus. FINDINGS: A 35-year-old man from Queensland had a brief
      aseptic meningitic illness in August, 1994, shortly after caring for two horses
      that died from EMV infection and then assisting at their necropsies. He then
      suffered severe encephalitis 13 months later, characterised by uncontrolled focal
      and generalised epileptic activity. Rising titres of neutralising antibodies to
      EMV in the patient's serum at the time of the second illness suggested an
      anamnestic response. Distinctive cortical changes were shown on magnetic
      resonance neuroimaging and histopathological examination of the brain at
      necropsy. Immunohistochemistry and electronmicroscopy of brain tissue revealed
      pathology characteristic of the earlier cases of EMV infection. PCR on
      cerebrospinal fluid taken during the second illness, brain tissue, and serum
      retained from the original illness resulted in an amplified product identical to
      that previously described from EMV. INTERPRETATION: The results of serology, PCR,
      electronmicroscopy, and immunohistochemistry strongly suggest that EMV was the
      cause of this patient's encephalitis, and that exposure to the virus occurred 3
      months before the fatal illness.

PMID- 8996422
TI  - A new syndrome of liver iron overload with normal transferrin saturation.
AB  - BACKGROUND: We investigated patients who had unexplained hepatic iron overload
      and normal transferrin saturation. METHODS: 65 patients with a median liver iron
      concentration of 65 mumol/g dry weight of liver (normal < 36 mumol/g),
      hyperferritinaemia (566 micrograms/L; normal < 400 micrograms/L), and normal
      transferrin saturations (32%) were compared with genetic haemochromatosis (GH)
      controls including homozygous (matched for sex and serum ferritin concentration)
      and heterozygous individuals. Relatives of patients who had ratios of liver iron
      concentration to age greater than 1.9 were also studied. FINDINGS: The 65
      patients were significantly older and had significantly less hepatic iron
      overload than individuals with genetic haemochromatosis. The frequency of HLA-A3
      antigen was significantly lower in these patients than in individuals with
      homozygous (p < 0.0001) or heterozygous (p < 0.0002) GH. Five HLA-identical
      siblings of the patients had normal serum ferritin concentrations. Most of the
      patients (95%) had one or more of the following conditions; obesity,
      hyperlipidaemia, abnormal glucose metabolism, or hypertension. INTERPRETATION: We
      have found a new non-HLA-linked iron-overload syndrome which suggests a link
      between iron excess and metabolic disorders. The current diagnostic criteria for
      genetic haemochromatosis should be reviewed.

PMID- 8996423
TI  - An unconscious man with asthma and a fixed, dilated pupil.

PMID- 8996424
TI  - Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy.

PMID- 8996425
TI  - Absence of rigor mortis in Indian childhood cirrhosis.

PMID- 8996426
TI  - Fatal toxic epidermal necrolysis associated with mefloquine antimalarial
      prophylaxis.

PMID- 8996427
TI  - Aberrant atrioventricular conduction triggered by antimalarial prophylaxis with
      mefloquine.

PMID- 8996428
TI  - 3-in-1 weight-monitoring chart.

PMID- 8996429
TI  - Hepatoblastoma in a 2-year-old child of a liver-transplanted mother.

PMID- 8996430
TI  - Multidrug-resistance to dapsone, rifampicin, and ofloxacin in Mycobacterium
      leprae.

PMID- 8996431
TI  - Precise localisation of single-word retrieval in the left cerebral hemisphere.

PMID- 8996432
TI  - Epithelial ovarian carcinoma.

PMID- 8996433
TI  - Biology of acute leukaemia.
AB  - The leukaemias vary in their response to therapy. In acute myeloid leukaemia, for
      instance, response to therapy is poorer in older than in younger patients. One
      explanation for this is that in older patients the acute myeloid leukaemia is
      more likely to have arisen from a pluripotent stem cell than from a lineage
      restricted progenitor cell; the former has a high self-renewal capacity, an
      active drug-efflux pump, and high content of anti-apoptotic proteins, all of
      which contribute to chemoresistance. Unravelling the biology of the leukaemias
      should help in the development of novel therapies.

PMID- 8996434
TI  - Puerperal priority.

PMID- 8996435
TI  - Evidence-based medicine: an incomplete method for informing treatment choices.

PMID- 8996436
TI  - Sexual assault on men in war.

PMID- 8996437
TI  - A step forward for opponents of female genital mutilation in Egypt.

PMID- 8996438
TI  - The Mayas of Guatemala: surviving terror.

PMID- 8996439
TI  - Cardioprotection and garlic.

PMID- 8996440
TI  - Cardioprotection and garlic.

PMID- 8996441
TI  - Cardioprotection and garlic.

PMID- 8996442
TI  - Need for pulmonary artery catheterisation guidelines.

PMID- 8996443
TI  - Pathophysiology of itching.

PMID- 8996445
TI  - Treatment of glue ear in general practice.

PMID- 8996444
TI  - Treatment of glue ear in general practice.

PMID- 8996446
TI  - Sudden unexplained death.

PMID- 8996447
TI  - Sudden unexplained death.

PMID- 8996448
TI  - Management of megaloblastic anaemia.

PMID- 8996449
TI  - Management of megaloblastic anaemia.

PMID- 8996450
TI  - Toxoid vaccine for pertussis.

PMID- 8996451
TI  - Toxoid vaccine for pertussis.

PMID- 8996452
TI  - Toxoid vaccine for pertussis.

PMID- 8996453
TI  - Prophylactic cranial irradiation for small-cell lung cancer.

PMID- 8996454
TI  - Chinese eugenic legislation.

PMID- 8996455
TI  - Thoughts for humble servants of science.

PMID- 8996456
TI  - Role of neurosurgeons in Japan.

PMID- 8996457
TI  - Potential antitussive effects of a computer antivirus program.

PMID- 8996459
TI  - A comparison of resource use and cost in direct access versus physician referral
      episodes of physical therapy.
AB  - BACKGROUND AND PURPOSE: Access to physical therapy in many states is contingent
      on prescription or referral by a physician. Other states have enacted direct
      access legislation enabling consumers to obtain physical therapy without a
      physician referral. Critics of direct access cite potential overutilization of
      services, increased costs, and inappropriate care. METHODS AND RESULTS: Using
      paid claims data for the period 1989 to 1993 from Blue Cross-Blue Shield of
      Maryland, a direct access state, we compiled episodes of physical therapy for
      acute musculoskeletal disorders and categorized them as direct access (n = 252)
      or physician referral (n = 353) using algorithms devised by a clinician advisory
      panel. Relative to physician referral episodes, direct access episodes
      encompassed fewer numbers of services (7.6 versus 12.2 physical therapy office
      visits) and substantially less cost ($1,004 versus $2,236). CONCLUSION AND
      DISCUSSION: Direct access episodes were shorter, encompassed fewer numbers of
      services, and were less costly than those classified as physician referral
      episodes. There are several potential reasons why this may be the case, such as
      lower severity of the patient's condition, overutilization of services by
      physicians, and underutilization of services by physical therapists. Concern that
      direct access will result in overutilization of services or will increase costs
      appears to be unwarranted.

PMID- 8996458
TI  - Drugs for treatment of peptic ulcers.

PMID- 8996460
TI  - Reliability of impairment and physical performance measures for persons with
      Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Parkinson's disease (PD) is characterized by rigidity,
      postural instability, bradykinesia, and tremor, as well as other musculoskeletal
      impairments and functional limitations. The purpose of this investigation was to
      determine the reliability and stability of measures of impairments and physical
      performance for people in the early and middle stages of PD, Subjects. Thirteen
      men and 2 women in Hoehn and Yahr stages 2 and 3 of PD participated. Their mean
      age was 74.5 years (SD = 5.7, range = 64-84). METHODS: Thirteen impairment-level
      variables and 8 physical performance variables were measured. Measurements were
      taken on two consecutive days and again a week later on the corresponding two
      consecutive days. Reliability and stability were assessed using analysis of
      variance and intraclass correlation coefficients (ICCs). RESULTS: Test-retest
      reliability (ICCs) of variables ranged from .69 (hamstring muscle length) to .97
      (lumbar flexion). Intraclass correlation coefficients were .85 or greater for 10
      of the variables. CONCLUSIONS AND DISCUSSION: The results suggest that in the
      early and middle stages of PD, many of the measures of impairment and physical
      performance are relatively stable.

PMID- 8996461
TI  - Effect of transcutaneous electrical nerve stimulation on the pressor response to
      static handgrip exercise.
AB  - BACKGROUND AND PURPOSE: A proposed mechanism for the pain-relieving properties of
      transcutaneous electrical nerve stimulation (TENS) is gating of impulses carried
      by group III and IV afferent nerve fibers. The purpose of this study was to
      determine the effects of TENS on the pressor response to static exercise, a
      response mediated by group III and IV muscle afferents. SUBJECTS: Sixteen
      subjects (9 men, 7 women) with no known history of cardiovascular, neurologic, or
      musculoskeletal disease participated. METHODS: We measured arterial pressure,
      heart rate, and sympathetic activity during sustained, 25% maximal handgrip
      exercise. Each subject performed the handgrip exercise with and without
      conventional TENS applied to the ipsilateral forearm and, in a separate trial, to
      the contralateral leg. RESULTS: The sympathetically mediated pressor response to
      handgrip exercise was blunted when TENS was applied to the ipsilateral forearm,
      but not when TENS was applied to the contralateral leg. CONCLUSION AND
      DISCUSSION: These data support the concept that central transmission of neural
      impulses traveling in group III and IV fibers can be modulated by other afferent
      inputs converging on the same spinal level.

PMID- 8996463
TI  - The effect of multidimensional exercises on balance, mobility, and fall risk in
      community-dwelling older adults.
AB  - BACKGROUND AND PURPOSE: This prospective clinical investigation examined the
      effects of a multidimensional exercise program on balance, mobility, and risk for
      falls in community-dwelling older adults with a history of falling. Factors used
      to predict adherence and a successful response to exercise were identified.
      SUBJECTS: A total of 105 community-dwelling older adults (> or = 65 years of age)
      with a history of two or more falls in the previous 6 months (no neurologic
      diagnosis) participated. They were classified into (1) a control group of fallers
      (n = 21), (2) a fully adherent exercise group (n = 52), and (3) a partially
      adherent exercise group (n = 32). METHODS: Following evaluation, each patient
      received an individualized exercise program addressing the impairments and
      functional disabilities identified during the assessment. The control group
      received no intervention. Changes in performance on five clinical tests of
      balance and mobility and fall risk were compared among groups. RESULTS: Both
      exercise groups scored better than the control group on all measures of balance
      and mobility. Although both exercise groups showed a reduction in fall risk
      compared with the control group, the greatest reduction was found in the fully
      adherent exercise group. Factors associated with successful response to exercise
      included degree of adherence to exercise program and pretest score on the Tinetti
      Mobility Assessment. CONCLUSION AND DISCUSSION: Exercise can improve balance and
      mobility function and reduce the likelihood for falls among community-dwelling
      older adults with a history of falling. The amount of exercise needed to achieve
      these results, however, could not be determined from this study.

PMID- 8996462
TI  - Opinions of physical therapy education program directors on essential functions.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the opinions
      of directors of physical therapy education programs concerning the essential
      functions physical therapist students must be able to complete, with or without
      reasonable accommodation. SUBJECTS: Fifty-eight physical therapy education
      program directors participated. METHODS: Participants completed surveys as part
      of a three-round Delphi technique. They had the opportunity to modify or make
      additions to the initial list in the first round and rate the items in the last
      two rounds using an ordinal scale. RESULTS: All participants rated communication
      skills and practicing in a safe, ethical, and legal manner as definitely
      essential functions. Nearly universal agreement (95%-99%) was present for
      determining physical therapy needs of patients with movement dysfunction and
      demonstrating the ability to apply universal precautions. Performance of
      treatment procedures and performance of assessment procedures were rated
      essential by 90% to 95% of the participants. The least agreement was found for
      participation in the process of scientific inquiry. CONCLUSION AND DISCUSSION:
      There is agreement among the physical therapy education program directors
      concerning the essential functions that should be required of students. The
      results of this study should serve as a reference for physical therapy education
      programs for developing the essential functions required of students.

PMID- 8996464
TI  - Diagnosis of trochanteric bursitis versus femoral neck stress fracture.
AB  - This case report describes a 46-year-old male runner who reported the sudden
      onset of right hip pain. A diagnosis of trochanteric bursitis was established by
      a physiatrist, and the patient underwent two courses of physical therapy for
      moist heat, ultrasound, and exercise. Because minimal improvement was seen in the
      patient's pain level and gait limitations following physical therapy, a
      consultation was requested of a fellow staff member in the same physical therapy
      department, who is both a chiropractor and a physical therapist. The consultant
      felt that the absence of tenderness to deep palpation of the greater trochanter,
      the presence of a noncapsular pattern of restriction of the right hip, and the
      patient's nonresponsiveness to physical therapy warranted further investigation.
      A differential diagnosis of avascular necrosis, fracture, or a loose body was
      made by the consultant. Magnetic resonance imaging (MRI) testing ordered by the
      consultant indicated a nondisplaced, complete stress fracture of the femoral
      neck. The results of the consultation and the MRI testing were communicated to
      the referring physiatrist. The patient was referred to an orthopedic surgeon, who
      performed an open reduction and internal fixation of the right hip. The patient
      was ambulatory without an assistive device or weight-bearing restrictions 5 weeks
      after surgery.

PMID- 8996466
TI  - Women's health.

PMID- 8996465
TI  - Fibromyalgia syndrome: an overview.

PMID- 8996467
TI  - Methotrexate update.
AB  - Methotrexate (MTX) has become one of the most widely prescribed second-line
      agents world-wide for rheumatoid arthritis (RA). Studies have established
      efficacy in populations which have failed other second-line agents. Although MTX
      must be considered as a potential hepatotoxin, studies have shown that liver
      histologic changes can be predicted by monitoring of serum albumin and AST at
      four to eight week intervals. MTX pulmonary toxicity appears to be more common
      than liver disease. It most often presents with a subacute course with dry cough
      and dyspnea with or without fever. Clinicians must be aware of this presentation
      and withhold the drug when these symptoms appear. MTX may also cause mild renal
      impairment when used with NSAIDs. This effect has been observed with higher mean
      weekly doses in the 15 to 20 mg range, but not with a starting dose of 7.5 mg.
      Although MTX may exhibit a variety of effects in in vitro systems its mechanism
      of action in patients with RA has not yet been determined.

PMID- 8996469
TI  - Anti-double stranded DNA antibodies in systemic lupus erythematosus: detection
      and clinical relevance of IgM-class antibodies.
AB  - We determined the discriminative value of the Farr assay in comparison to ELISA
      and Crithidia luciliae immunofluorescence assay (IFT) for detecting anti-dsDNA
      antibodies as a diagnostic tool for systemic lupus erythematosus (SLE). Special
      attention was paid to the diagnostic significance of IgM-class anti-dsDNA. Sera
      were analyzed from 74 patients with SLE, 257 patients with other auto-immune
      diseases, and 50 healthy controls. All sera were tested for anti-dsDNA using the
      IFT (anti-total immunoglobulin conjugate), ELISA (anti-IgG and anti-IgM
      conjugates), and the 125I Farr assay. Specificity and sensitivity for a diagnosis
      of SLE appeared to be highest for the Farr. All SLE sera with IgM-class anti
      dsDNA without IgG-class anti-dsDNA as detected by ELISA, were positive when
      tested by the Farr assay. In contrast, most of the sera with IgM-class anti-dsDNA
      as detected by ELISA from patients with diseases other than SLE were negative
      when tested by Farr assay.

PMID- 8996468
TI  - Tenidap in patients with rheumatoid arthritis. A 4-week, placebo-controlled
      study.
AB  - The present double-blind, placebo-controlled study was conducted to compare the
      safety and efficacy of tenidap in patients with rheumatoid arthritis (RA).
      Patients with flare of active RA following NSAID withdrawal were randomized to
      receive either placebo (n = 67) or tenidap (n = 131; 40-200 mg/day). The mean
      changes from baseline in efficacy and biochemical variables were compared between
      treatment groups at endpoint (4 weeks). The improvements in four of the five
      primary efficacy variables were significantly greater in the tenidap group
      compared with the placebo group (p < 0.01). Tenidap was also associated with an
      18% reduction in erythrocyte sedimentation rate (ESR) and a marked, 51%,
      reduction in serum C-reactive protein (CRP) level, both of which were
      significantly greater than the changes in the placebo group (p < 0.05). The
      percentage of patients who discontinued because of side effects was the same in
      both groups (3%). In conclusion, tenidap 40-200 mg/day was effective and well
      tolerated in the treatment of patients with RA for 4 weeks.

PMID- 8996470
TI  - Clinical outcome after one year following samarium-153 particulate hydroxyapatite
      radiation synovectomy.
AB  - The clinical outcome and tolerability following treatment with samarium-153
      particulate hydroxyapatite was evaluated in patients with persistent rheumatoid
      knee synovitis. The clinical review of 18 patients treated with intra-articular
      samarium-153 particulate hydroxyapatite combined with triamcinolone hexacetonide
      who had failed to obtain more than 4 weeks symptom relief from a prior intra
      articular glucocorticoid injection was undertaken. No unwanted effects from the
      treatment were observed. Symptom relief was maintained in 56% patients at 6
      months and in 44% of patients at 12 months following treatment. Median duration
      of symptom relief was 9 months. There was a significantly higher mean baseline
      Ritchie Articular Index in patients relapsing within 3 months and a trend towards
      earlier relapse in patients with higher indices of disease activity at the time
      of treatment. There was a trend towards earlier relapse in patients with a poor
      range of knee flexion at baseline and with worse indices of intra-articular
      radiopharmaceutical distribution. Samarium-153 particulate hydroxyapatite knee
      synovectomy is well tolerated and may be an effective treatment for carefully
      selected patients with persistent rheumatoid knee synovitis.

PMID- 8996471
TI  - Bone loss in rheumatoid arthritis. Influence of disease activity, duration of the
      disease, functional capacity, and corticosteroid treatment.
AB  - Axial and appendicular bone mass were studied in 95 patients with rheumatoid
      arthritis. The aims were to quantify bone mineral density (BMD) and to evaluate
      the importance of disease activity, duration of disease, functional capacity, and
      corticosteroid treatment for bone loss in patients with rheumatoid arthritis. The
      BMD in the lumbar spine (BMDSPINE) did not differ from age-matched healthy
      controls, but distal forearm BMD (BMDARM) and metacarpal BMD (BMDMCB) were
      significantly lower in the patients (p < 0.01 and p < 0.001, respectively).
      Neither BMDSPINE nor BMDMCB were related to the disease activity at the time of
      investigation. By contrast, BMDARM was decreased in patients with active disease.
      BMD in any of the three measured locations was not directly correlated to
      duration of the disease. However, the bone mass in the appendicular skeleton was
      already decreased within the first two years after the start of the disease. The
      overall functional capacity in terms of physical activity increased BMD in the
      axial skeleton. The local functional capacity in terms of grip strength was
      positively related to BMD in the appendicular skeleton. Patients with severe
      functional impairment had the lowest BMDARM. The decreased BMD in patients with
      rheumatoid arthritis seems primarily to be caused by an impaired physical
      activity which may be related to disease activity. Corticosteroids did not
      decrease BMD in neither the axial nor the appendicular skeleton. The
      antiinflammatory effect of steroids lead to clinical improvement, which may
      counteract the expected negative effect of these drugs on bone in rheumatoid
      arthritis.

PMID- 8996472
TI  - The impact of early rheumatoid arthritis on psychological distress. A comparison
      between 238 patients with RA and 116 matched controls.
AB  - The objective of our study was to estimate the impact of early rheumatoid
      arthritis (RA) on psychological distress by comparing patients with RA and
      matched controls. A sample of 238 patients (age 20-70 years, mean age 52 yrs)
      with RA of 0 to 4 years duration (mean 2.2 yrs), was compared to 116 control
      persons matched to the patients with respect to sex, age, and geographic area.
      Data were collected through self-report questionnaires. Patients with RA rated
      their mental health significantly lower than the controls. Symptoms of anxiety
      and depression were significantly higher among arthritic patients. Twenty% of the
      patients had scores indicating possible psychiatric caseness compared to 6% of
      the controls. However, controlling for pain, disability, and fatigue, there was
      no significant difference in psychological distress between the patients and the
      controls. RA appears to have a strong impact on mental distress even early in the
      disease. The present study demonstrates that pain, disability, and fatigue are
      strongly related to the increased levels of psychological distress in RA.

PMID- 8996473
TI  - Undernutrition in rheumatoid arthritis patients with disability.
AB  - Clinical evaluation of nutritional status (NS) was performed in 75 rheumatoid
      arthritis patients. They were distributed according to functional class,
      radiological stage and other prognostic factors (rheumatoid factor,
      extraarticular disease, disease duration). Evaluation of the different
      anthropometrical measurements in this group of long-standing RA patients (average
      disease duration: 10 years) revealed a significant impairment of lean body mass
      (LBM), especially among those with greater disability (Functional Class III and
      IV). Patients in more severe radiological stages (Radiological Stage III and IV)
      or patients with extraarticular disease also presented a significant loss of LBM
      compared with a matched cohort of the general population and patients with a more
      benign-course disease. There was less impairment of the fat mass, according to
      our clinical evaluation. Serological parameters of undernutrition (albumin and
      transferrin) did not show significant differences among the groups of patients.
      Clinical evaluation of NS in RA patients is a useful procedure for recognising
      patients at high risk of related complications by means of their poor nutritional
      status.

PMID- 8996474
TI  - Multiple lymphadenopathy induced by wear debris after total knee replacement.
AB  - Lymphadenopathy induced by wear debris after total joint arthroplasty is very
      rare. In this article we report on a patient with rheumatoid arthritis who
      developed multiple lymphadenopathy after total knee joint replacement.

PMID- 8996475
TI  - Renal cell carcinoma associated with cyclophosphamide therapy for Wegener's
      granulomatosis.
AB  - Cyclophosphamide therapy may be associated with the subsequent development of
      malignacies in many organs including the urinary tract. The main site in the
      urinary tract for development of these malignancies is the urinary bladder.
      Carcinoma of the kidney associated with cyclophosphamide therapy has previously
      been reported only in transplant recipients. The present case describes, for the
      first time, the development of renal cell carcinoma after treatment with
      cyclophosphamide in a patient with Wegener's granulomatosis.

PMID- 8996476
TI  - Bilateral blindness in Takayasu's disease.
AB  - We report the case of a 61-year-old woman who presented bilateral blindness at
      the age of nineteen. Although she did not receive any treatment, she did not
      present any other symptoms through 40 years of follow-up. After reviewing the
      literature, we have not found any case of bilateral blindness as the first
      manifestation of TD without further progression of the disease despite the
      absence of treatment.

PMID- 8996477
TI  - Probability of the development of non-Hodgkin's lymphoma in primary Sjogren's
      syndrome.

PMID- 8996478
TI  - Early hemorrhage growth in patients with intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: The goal of the present study was to prospectively
      determine how frequently early growth of intracerebral hemorrhage occurs and
      whether this early growth is related to early neurological deterioration.
      METHODS: We performed a prospective observational study of patients with
      intracerebral hemorrhage within 3 hours of onset. Patients had a neurological
      evaluation and CT scan performed at baseline, 1 hour after baseline, and 20 hours
      after baseline. RESULTS: Substantial growth in the volume of parenchymal
      hemorrhage occurred in 26% of the 103 study patients between the baseline and 1
      hour CT scans. An additional 12% of patients had substantial growth between the 1
      and 20-hour CT scans. Hemorrhage growth between the baseline and 1-hour CT scans
      was significantly associated with clinical deterioration, as measured by the
      change between the baseline and 1-hour Glasgow Coma Scale and National Institutes
      of Health Stroke Scale scores. No baseline clinical or CT prediction of
      hemorrhage growth was identified. CONCLUSIONS: Substantial early hemorrhage
      growth in patients with intracerebral hemorrhage is common and is associated with
      neurological deterioration. Randomized treatment trials are needed to determine
      whether this early natural history of ongoing bleeding and frequent neurological
      deterioration can be improved.

PMID- 8996479
TI  - Outcome of aneurysmal subarachnoid hemorrhage in patients on anticoagulant
      treatment.
AB  - BACKGROUND AND PURPOSE: Intracranial hemorrhage is an important complication of
      treatment with anticoagulants. We studied outcome of aneurysmal subarachnoid
      hemorrhage (SAH) occurring in patients on anticoagulant drugs because this may
      influence management of patients needing anticoagulant treatment but with
      increased risk of aneurysmal hemorrhage. METHODS: From the prospective database
      of patients admitted with SAH to the Utrecht University Hospital, we compared 3
      month outcome in patients with or without anticoagulant drugs by means of
      stratified analyses to adjust relative risks for biological and clinical
      differences between the two groups. RESULTS: Death or dependency after SAH
      occurred in 14 of 15 patients on anticoagulant treatment and in 62 of 126
      patients not being treated with anticoagulants (relative risk, 1.9; 95%
      confidence interval, 1.5 to 2.4). The patients on treatment with anticoagulants
      were more often comatose on admission; the frequencies of rebleeding, secondary
      ischemia, and hydrocephalus were not higher in patients on anticoagulants. In the
      stratified analysis the worse outcome in the group on anticoagulant drugs was not
      essentially influenced by differences in sex, age, cardiovascular history, site
      of aneurysm, amount of cisternal blood, or extension of hemorrhage into the
      ventricles. CONCLUSIONS: The outcome of aneurysmal SAH in patients or
      anticoagulant drugs is extremely poor. The explanation for the worse prognosis in
      patients on anticoagulants lies in a worse clinical condition from the outset.
      The poor outcome urges a reconsideration of the balance of risks for
      anticoagulant treatment in patients with an unoperated intracranial aneurysm or
      with a family history of SAH and may lead to withholding treatment with
      anticoagulant drugs or to a preventive operation.

PMID- 8996480
TI  - Acute ischemic strokes improving during the first 48 hours of onset:
      predictability, outcome, and possible mechanisms. A comparison with early
      deteriorating strokes.
AB  - BACKGROUND AND PURPOSE: Our aims were to identify predictors of early
      neurological improvement in acute ischemic stroke patients, to evaluate its
      impact on clinical outcome, and to investigate possible mechanisms. METHODS: A
      consecutive series of 152 first-ever ischemic hemispheric stroke patients
      hospitalized within 5 hours of onset underwent a first CT scan within 1 hour of
      hospitalization, and the initial subset of 80 patients also underwent
      angiography. During the first 48 hours of hospital stay, an increase or a
      decrease of 1 or more points in the admission Canadian Neurological Scale (CNS)
      score was defined as early improvement or early deterioration, respectively.
      Repeated CT scan or autopsy was performed 5 to 9 days after stroke. RESULTS:
      Thirty-four patients (22%) improved, 84 (56%) remained stable, and 34 (22%)
      deteriorated. Logistic regression, which took into account vascular risk factors,
      baseline clinical and CT data, and therapies administered, selected younger age,
      lower admission CNS score, and absence of early hypodensity at first CT as
      independent predictors of early improvement. Among the patients who underwent
      angiography, logistic regression selected arterial patency and presence of
      collateral blood supply as independent predictors of early improvement. At the
      repeated CT scan or autopsy, improving patients presented the highest frequency
      of small infarcts. Thirty-day case-fatality rate and disability were lower in
      improving patients. Variables independently associated with outcome at logistic
      regression were admission CNS score, early deterioration, and early improvement.
      CONCLUSIONS: Early improvement can be predicted by the absence of early CT
      hypodensity and is highly predictive of good outcome. Presence of collateral
      blood supply and presumably early spontaneous recanalization are likely to be the
      mechanisms underlying early improvement.

PMID- 8996481
TI  - African Americans and women have the highest stroke mortality in Texas.
AB  - BACKGROUND AND PURPOSE: Hispanic American (HA), African American (AA), and non
      Hispanic white (NHW) populations are well represented in Texas. The Texas HA
      population is 95% Mexican American, affording comparison with other Hispanic
      populations. From risk factor profiles we expected stroke mortality to be highest
      in AAs and HAs. We also expected stroke mortality to be considerably higher for
      men than for women based on previous data. METHODS: We used International
      Classification of Diseases, 9th Revision, codes 430 to 438 to search Texas vital
      statistics data for the 5-year period from 1988 through 1992. Race/ethnic
      differences are presented in age- and sex-specific format to avoid masking the
      important interaction of age and sex with stroke mortality. RESULTS: Women
      constituted 61% of the 40,346 stroke deaths in Texas during this period. The
      ratio of stroke deaths for women versus men approximates the ratio of women to
      men in the population. AAs had a threefold to fourfold increased stroke mortality
      relative to NHWs at young ages. At older ages, when stroke mortality is the
      highest, the stroke mortality rate in NHWs approached the stroke mortality rate
      of AAs. HAs had a significantly higher rate of stroke mortality at younger ages
      relative to NHWs but a significantly lower rate at older ages. CONCLUSIONS:
      Measures to prevent stroke mortality should emphasize its predilection for young
      AAs and women. A rigorous surveillance project is needed to determine whether
      stroke mortality is underestimated in the HA population.

PMID- 8996482
TI  - Racial differences in the utilization of inpatient rehabilitation services among
      elderly stroke patients.
AB  - BACKGROUND AND PURPOSE: We undertook this study to ascertain whether elderly
      black and white patients who are hospitalized for stroke utilize inpatient
      physical and occupational therapy (PT/OT) services differently, adjusting for
      characteristics associated with use of these services. METHODS: We
      retrospectively reviewed medical records regarding the care received by a
      nationally representative sample of 2497 black and white Medicare patients, aged
      65 years of older, who were hospitalized at any of 297 acute-care hospitals
      located in 30 communities within five states. RESULTS: Compared with whites,
      black stroke patients were younger and more likely to have Medicaid coverage,
      have an ischemic stroke, and have a motor deficit noted at the time of admission.
      There was no difference in either sex or level of consciousness on admission.
      Overall, a larger proportion of black stroke patients used inpatient PT/OT at
      some point during the hospitalization (66.3% versus 55.8%; P < .01). However,
      after adjustment for characteristics associated with use of PT/OT, there was no
      racial difference in either the likelihood of inpatient PT/OT use (adjusted
      relative risk, 1.06; 95% confidence limits, 0.89 to 1.27; P = .42) or time to
      initial contact (median: blacks, 6.6 days; whites, 7.4 days; P = .42). Adjusted
      analyses also indicated a similarity between the racial groups in the number of
      inpatient PT/OT days overall or as a proportion of the hospital stay.
      CONCLUSIONS: Elderly black and white stroke patients who have Medicare coverage
      have similar patterns of use of inpatient PT/OT services.

PMID- 8996483
TI  - Lifestyle-associated risk factors for acute brain infarction among persons of
      working age.
AB  - BACKGROUND AND PURPOSE: This study was designed to identify whether cigarette
      smoking, alcohol drinking, obesity, and use of oral contraceptives are
      independent risk factors for brain infarction among persons of working age.
      METHODS: Health habits and previous diseases of 506 patients (366 men and 140
      women aged 16 to 60 years) with acute first-ever symptomatic brain infarction
      were compared with those of 345 hospitalized control patients (219 men and 126
      women) who did not differ from case subjects in respect to day of onset of
      symptoms or acuteness of disease onset. With the use of stepwise logistic
      regression, the variables for which the simultaneous risks of acute brain
      infarction were tested by sex were age, amount of alcohol consumed within 24
      hours and 1 week before the illness, heavy drinking, smoking status, current
      smoking, cardiac disease, hypertension, diabetes, hyperlipemia, migraine, body
      mass index, and, in women, current use of oral contraceptives. RESULTS: Intake of
      > 40 g ethanol within the 24 hours preceding the onset of illness increased the
      risk for acute brain infarction both among men (P < .001) and women (P < .01)
      independently from other risk factors. Other significant independent risk factors
      for brain infarction among men were hypertension (P < .001), cardiac disease (P <
      .01), current smoking (P < .01), diabetes (P < .05), and history of migraine (P <
      .05) and among women, current use of oral contraceptives (P < .01) and current
      smoking (P < .05). CONCLUSIONS: Recent heavy drinking of alcohol, hypertension,
      cardiac disease, current smoking, diabetes, and history of migraine among men,
      and recent heavy drinking of alcohol, current use of oral contraceptives, and
      current smoking among women, seem to be independent risk factors for acute brain
      infarction.

PMID- 8996484
TI  - Ambulatory blood pressure monitoring in acute stroke. The West Birmingham Stroke
      Project.
AB  - BACKGROUND AND PURPOSE: Ambulatory blood pressure monitoring (ABPM) devices are
      increasingly used in the assessment of hypertension, but their value in patients
      after a stroke is unknown, despite the fact that hypertension is an important
      cause of stroke and many patients have relatively high blood pressure (BP) levels
      at presentation. We therefore investigated the clinical use of a 24-hour
      oscillometric ABPM device in patients after acute stroke. We also investigated
      ABPM in different types of stroke (thrombosis, hemorrhage, and transient ischemic
      attack) and ethnic and sex differences. METHODS: BP was measured manually with a
      standard mercury sphygmomanometer, and ABPM measurements were made with an
      oscillometric device. The first reading obtained with the ABPM device was
      compared with simultaneous manual BP measurements. Mean daytime and nighttime
      pressures were also analyzed to determine the frequency of nocturnal BP falls
      ("dipping"). RESULTS: We studied 86 patients (48 men; mean +/- SD age, 64.2 +/-
      9.2 years) admitted with acute-onset stroke (ictus within 12 hours) in a district
      general hospital. Thirty-one patients (36.0%) had a previous history of
      hypertension. The median percentage of successful BP readings by ABPM was 92%
      (interquartile range, 72 to 98). There was no significant difference in manual BP
      levels compared with the first simultaneous systolic or diastolic ABPM
      measurements. Systolic BPs recorded by ABPM were significantly higher in black
      patients with acute stroke and in patients with intracerebral hemorrhage, who
      also showed a trend toward higher nocturnal BPs. There was no difference in BPs
      between men and women and those who were alive or dead 6 months later (P = NS).
      There was also no difference between mean day and night systolic BP (mean
      difference, 1.9 mm Hg; P = .08), although mean daytime diastolic BP was higher
      than mean nighttime diastolic BP (mean difference, 2.4 mm Hg; P = .01). Patients
      with stroke therefore demonstrated a loss of diurnal BP rhythm and may be
      considered "nondippers"; there was also a trend toward "reverse dipping" in
      patients with intracranial hemorrhage. CONCLUSIONS: This study demonstrates
      higher systolic BPs as recorded by ABPM (but not manually) in patients with
      intracerebral hemorrhage than in those with cerebral infarcts; higher levels were
      also found in blacks. ABPM recordings are useful in the assessment of BP in
      patients with stroke, who may be considered nondippers.

PMID- 8996485
TI  - Vascular events during follow-up in patients with aortic arch atherosclerosis.
AB  - BACKGROUND AND PURPOSE: An association between aortic arch atherosclerosis and
      vascular events has been demonstrated. However, few data exist regarding follow
      up evaluation of this disease. METHODS: In this study, 183 patients with the
      diagnosis of aortic arch atherosclerosis were prospectively followed up. This
      diagnosis was made during an echocardiographic cross-sectional study. In 136
      patients, raised plaques with thickness < 5 mm had been shown to exist, and in 47
      patients complex plaques with thickness > or = 5 mm or plaques with mobile
      components had been demonstrated on the initial transesophageal echocardiography.
      RESULTS: During a mean follow-up period of 16 +/- 7 months, vascular events with
      a presumed embolic origin occurred in 15 patients. The incidence was 4.1 per 100
      person-years in patients with raised plaques compared with 13.7 per 100 person
      years in the group with complex plaques. The Kaplan-Meier survival analysis
      revealed a significantly higher rate of vascular events in patients who were
      found to have complex plaques (P < .01). In the Cox proportional hazards
      analysis, the finding of complex plaques (relative risk [RR], 4.3; 95% confidence
      interval [CI], 1.5 to 12.0; P = .006), coronary artery disease (RR, 4.0; 95% CI,
      1.2 to 13.1; P = .02), and a history of previous embolism (RR, 4.0; 95% CI, 1.1
      to 14.4; P = .03) were independent predictors of vascular events. CONCLUSIONS:
      Patients with the finding of protruding plaques or plaques with mobile components
      have a high risk of subsequent vascular events.

PMID- 8996486
TI  - Effect of age, birth cohort, and period of death on cerebrovascular mortality in
      Spain, 1952 through 1991.
AB  - BACKGROUND AND PURPOSE: The continued decrease in cerebrovascular disease in
      Spain remains unexplained. Age-period-cohort analysis enables description of
      birth cohort and period-of-death components. This study sought to describe these
      effects on the decline of stroke mortality in Spain. METHODS: Deaths due to
      cerebrovascular diseases in the period from 1952 through 1991 and the
      corresponding population figures were grouped into 11 age groups and 8 5-year
      periods, from which age-specific mortality rates for 18 birth cohorts were then
      computed. These were plotted for graphical presentation purposes and fitted to
      Poisson regression models to assess age, period, and cohort effects. RESULTS: An
      exponential age effect was present for both sexes regardless of cohort or period.
      A definite downward period effect was observable from 1962 to 1991, except for a
      sharp fall and peak in the periods 1967 to 1971 and 1972 to 1976, respectively,
      which was possibly ascribable to changes in diagnostic and coding practices. Age-
      and period-adjusted stroke mortality increased for earlier cohorts and decreased
      for generations born between 1892 and 1940. For post-1940 generations, there was
      an increasing risk of stroke mortality. CONCLUSIONS: The results suggest that a
      decrease in incidence coupled with an increase in survival may account for the
      observed decline in stroke mortality, but further studies on the Spanish
      population are needed to assess these findings. Although not yet definitive,
      there are signs of an increase in incidence among the more recent generations. If
      the decreasing period effect fails to offset this increase, future years may see
      a deceleration in the current decline in stroke mortality.

PMID- 8996487
TI  - A 15.5-year follow-up study of stroke in a Japanese provincial city. The Shibata
      Study.
AB  - BACKGROUND AND PURPOSE: Change toward Western lifestyles, particularly during the
      high economic growth period (approximately 1960 to 1975), dynamically altered
      stroke frequency and the distribution of risk factors in the Japanese. We
      reexamined their association after this environmental change by a cohort study.
      METHODS: The cohort (2302 subjects) comprised residents aged 40 years or older of
      the Akadani-Ijimino district in Shibata City, Niigata Prefecture, Japan, who were
      followed up from 1977 for 15.5 years. RESULTS: Crude incidence rates per 1000
      person-years for all strokes were 5.22 for men and 4.36 for women (3.02 and 2.18
      for cerebral infarction, 0.65 and 1.06 for intracerebral hemorrhage, and 0.41 and
      0.34 for subarachnoid hemorrhage, respectively). Multivariate analyses performed
      with the Cox proportional hazard model revealed these risk factors to be
      independently significant: for cerebral infarction in men, age, blood pressure,
      atrial fibrillation, albuminuria, funduscopic abnormality, and current smoking:
      for cerebral infarction in women, age, atrial fibrillation, and history of
      ischemic heart disease; for intracerebral hemorrhage in men, age and funduscopic
      abnormality; for intracerebral hemorrhage in women, age, blood pressure, and
      light physical activity; for all strokes in men, age, blood pressure, atrial
      fibrillation, albuminuria, funduscopic abnormality, current smoking, and heavy
      physical activity; and for all strokes in women, age, atrial fibrillation, and
      light physical activity. CONCLUSIONS: Most traditional risk factors, including
      blood pressure and its related organ diseases, were confirmed, but serum total
      cholesterol had almost no effect. Physical activity had both negative and
      positive effects on stroke risk. In these findings, however, some differences
      related to sex were also observed.

PMID- 8996488
TI  - Geographic distribution of stroke mortality among immigrants to the United
      States.
AB  - BACKGROUND AND PURPOSE: This study examines the geographic distribution of stroke
      mortality among immigrants and natives of the United States. METHODS: National
      Center for Health Statistics and Bureau of the Census data were used to determine
      the geographic distribution of age-adjusted, race-, and race/sex-specific stroke
      mortality rates among immigrants and natives of the United States for 1979 to
      1981. RESULTS: For whites and blacks and for each of the respective race/sex
      groups, immigrants had markedly and highly statistically significantly lower age
      adjusted stroke mortality rates than either the entire US-born resident
      population or the US-born interregional migrant population. The spatial pattern
      of immigrant rates did not parallel the patterns for US-born populations.
      Immigrant rates were highest in the West and lowest in the Midwest for whites and
      highest in the Midwest and lowest in the Northeast for blacks, whereas for both
      US-born whites and blacks, resident and native rates were highest in the South
      and lowest in the Midwest. With few exceptions, region-specific immigrant rates
      for whites and blacks were significantly lower than rates for either US-born
      regional residents, US-born migrants to the regions, or US-born natives of the
      regions. In contrast, white immigrants to the West had significantly higher rates
      than US-born groups in that region. CONCLUSIONS: Selection factors strongly
      influence stroke mortality rates among immigrants to the United States. The
      aberrantly high rates among white immigrants to the West may in part reflect a
      bias due to large census undercounts of this population.

PMID- 8996489
TI  - Prevalence and risk factors of incontinence after stroke. The Copenhagen Stroke
      Study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate in a
      community-based population the prevalence of both urinary (UI) and fecal (FI)
      incontinence and to analyze risk factors by means of multivariate analysis.
      METHODS: Included were 935 acute stroke patients admitted consecutively during 19
      months. We evaluated UI and FI using subscores of the Barthel Index during the
      hospital stay and at 6-month follow-up. RESULTS: On admission, the proportions of
      patients with full UI, partial UI, and no UI were 36%, 11%, and 53%, respectively
      (8%, 11%, and 81% at 6-month follow-up). The proportions of patients, with full
      FI, partial FI, and no FI on admission were 34%, 6%, and 60%, respectively (5%,
      4%, and 91% at 6-month follow-up). By multivariate analysis, significant risk
      factors for UI and FI were age, severity of stroke, diabetes, and comorbidity of
      other disabling diseases. CONCLUSIONS: On admission in the acute state, almost
      half of an unselected stroke population have UI and/or FI. The proportion
      declines to one fifth (UI) and one tenth (FI) of the surviving patients at 6
      months. Increasing age, stroke severity, diabetes, and other disabling diseases
      increase the risk of UI as well as FI.

PMID- 8996490
TI  - Prevalence of asymptomatic retinal emboli in an Australian urban community.
AB  - BACKGROUND AND PURPOSE: Because no population-based estimates are available for
      asymptomatic retinal emboli, we aimed to assess prevalence and associations of
      this sign in a defined older Australian urban population. METHODS: A total of
      3654 persons aged 49 years or older, representing 82% of residents in an urban
      area west of Sydney, underwent a detailed eye examination that included medical
      history, stereo retinal photography, and fasting blood tests including lipids.
      Retinal emboli were diagnosed clinically and from photographic grading and
      classified as cholesterol, platelet-fibrin, or calcific in type. RESULTS:
      Asymptomatic retinal emboli were found in 51 participants (1.4%; 95% confidence
      interval [CI], 1.0% to 1.8%). The prevalence was 0.8% in persons aged < 60 years,
      1.4% for those aged 60 to 69 years, 2.1% for those aged 70 to 79 years, and 1.5%
      for those aged 80 years or older. Men had a significantly higher prevalence
      (2.2%) of retinal emboli than women (0.8%, P < .001) after adjustment for age
      (odds ratio [OR], 2.7; 95% CI, 1.5 to 4.8). Forty-one emboli (80%) were
      cholesterol type, 7 (14%) were platelet-fibrin, and 3 (6%) were calcific.
      Significant associations were found after age-sex adjustment, with hypertension
      (OR, 2.2; 95% CI, 1.2 to 3.8), a combined history of vascular disease (OR, 2.4;
      95% CI, 1.3 to 4.4), past vascular surgery (OR, 3.5; 95% CI, 1.4 to 8.5), and
      current (OR, 2.2; 95% CI, 1.1 to 4.2) or any (OR, 2.6; 95% CI, 1.2 to 4.3),
      smoking history. These associations persisted after multivariate analysis. There
      were no significant associations with diabetes, obesity, or fasting blood test
      findings. CONCLUSIONS: This study provides accurate prevalence rates for
      asymptomatic retinal emboli in the elderly and confirms associations with
      hypertension, smoking, and vascular disease.

PMID- 8996491
TI  - Localization of lesion in denial of hemiplegia after acute stroke.
AB  - BACKGROUND AND PURPOSE: Previous studies of lesion localization in dental of
      hemiplegia have often been confounded by factors such as the cerebral etiology,
      which aspects of the disorder are denied, and whether delusions are present. Our
      investigation focuses on denial of hemiplegia, without concomitant delusions,
      after cerebrovascular accident (CVA). METHODS: The CT scans of 30 patients with
      denial of hemiplegia after acute stroke were compared with those from 10 CVA
      patients with hemiplegia and visuospatial neglect but no denial. Lesion sites
      were detailed using the templates of Damasio and Damasio and, for the deep
      structures, those of Talairach and Tournoux. RESULTS: Analysis of the CT scans
      demonstrated that 26 of 30 denial patients had unilateral right-sided lesions and
      that this group showed a significantly higher incidence of lesions in deep white
      matter and the basal ganglia. CONCLUSIONS: The results are discussed in relation
      to recent ideas regarding the role of the basal ganglia and subcortical circuits
      in movement and executive function.

PMID- 8996492
TI  - Thromboembolism prophylaxis in chronic atrial fibrillation. Practice patterns in
      community and tertiary-care hospitals.
AB  - BACKGROUND AND PURPOSE: By 1992, several prospective trials established the
      efficacy of anticoagulation (AC) and to some extent antiplatelet (AP) agents in
      the prevention of stroke in the setting of atrial fibrillation (AF). The
      objective of this study was to determine whether practice patterns in AF stroke
      prophylaxis reflect the findings of clinical trials and whether stroke
      prophylaxis in AF differs between community hospitals and tertiary teaching
      hospitals. METHODS: Retrospectively, 1250 hospital charts were reviewed. After
      patients who had undergone recent surgery, received treatment for malignancy, or
      were not in chronic AF on discharge were eliminated, 651 remaining records were
      analyzed for the presence of 26 clinical factors influencing the selection of
      thromboembolism prophylaxis. Descriptive statistics and logistic regression were
      used to analyze the association between clinical and demographic factors and the
      decision to treat with AC, AP, or no specific antiembolic therapy. RESULTS: Of
      the 651 patients in AF, 273 (42%) received noemboli prophylaxis while 219 (34%)
      were treated with AC (warfarin), 146 (22%) were treated with AP, and 13 (2%)
      received both agents. Patients discharged in AF from community hospitals were
      significantly less likely to be treated with either AC or AP agents than patients
      discharged from tertiary centers. A strong bias against thromboembolism
      prophylaxis with either AC or AP agents in AF existed with age over 45 years.
      Multivariate logistic regression indicated that the decision to treat was
      associated only with the presence of prosthetic valve, history of prior stroke,
      mitral disease, and absence of a recent gastrointestinal bleed or occult blood in
      stool. Even after adjustment for these factors, a significant bias against
      treatment with either AC or AP agents with advancing age and discharge from
      community hospitals remained. CONCLUSIONS: Thromboembolism prophylaxis with
      either AC or AP agents is underutilized in the setting of AF. Furthermore,
      factors known to increase the risk of embolization in AF such as age,
      hypertension, diabetes, and heart disease were not associated with decisions to
      treat with either AP or AC agents. This study suggests that the use of clinical
      guidelines suggested by trials of thromboembolism prophylaxis in AF could reduce
      the incidence of stroke.

PMID- 8996493
TI  - Focal expression of intercellular adhesion molecule-1 in the human carotid
      bifurcation.
AB  - BACKGROUND AND PURPOSE: In the carotid bifurcation, atherosclerotic plaques
      usually develop in the outer wall of the internal carotid artery. The aim of this
      study was to analyze the expression of the cell adhesion molecules intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E
      selectin in the carotid bifurcation. These molecules play a role in inflammatory
      cell recruitment and atherosclerosis. METHODS: We examined the expression of ICAM
      1, VCAM-1, and E-selectin in 22 human carotid bifurcation specimens by means of
      immunohistochemistry. Double immunostaining was performed with antibodies against
      CD-3, CD-31, CD-68, and alpha-smooth muscle actin combined with each of the cell
      adhesion molecule antibodies. In situ hybridization for ICAM-1 was performed in
      selected specimens. RESULTS: A profound focal expression of ICAM-1 in the outer
      wall of the internal carotid artery could be demonstrated (86% of all specimens).
      This focal expression could be shown in histologically normal appearing
      bifurcations of young adults. ICAM-1 was expressed by subsets of macrophages and
      smooth muscle cells and by endothelial cells. VCAM-1 and E-selectin showed no
      focal expression and were not found in normal carotids. In advanced plaques all
      three adhesion molecules-ICAM-1, VCAM-1, and E-selectin-were expressed.
      CONCLUSIONS: We were able to demonstrate a focal expression of ICAM-1 in the
      outer lateral wall of the internal carotid artery, which is a high-risk region
      for the development of atherosclerotic lesions.

PMID- 8996494
TI  - High-density lipoprotein cholesterol and risk of ischemic stroke mortality. A 21
      year follow-up of 8586 men from the Israeli Ischemic Heart Disease Study.
AB  - BACKGROUND AND PURPOSE: While there is overwhelming evidence relating low levels
      of HDL cholesterol (HDL-C) with coronary heart disease, the association with
      cerebrovascular disease is not clear. The aim of the present report was to assess
      the association between HDL-C levels and ischemic stroke mortality obtained from
      a long-term follow-up in the Israeli Ischemic Heart Disease Study. METHODS: The
      subjects of this report are 8586 men, tenured civil servants and municipal
      employees, aged 42 years or older at the time of HDL-C measurements in 1965. They
      were followed up for mortality for 21 years. Death due to cerebrovascular disease
      included the International Classification of Disease, 9th Revision, codes 430 to
      438, of which presumed ischemic stroke included codes 433 to 438. RESULTS: During
      the 21-year follow-up, 295 men died from cerebrovascular events, of which 241
      deaths were due to presumed ischemic stroke. Individuals subsequently
      experiencing a fatal ischemic stroke had a marginally lower age-adjusted mean HDL
      C (1.05 mmol/L) and a significantly lower (P < .001) age-adjusted mean percentage
      of serum cholesterol contained in the HDL fraction (%HDL) (19.3%) than
      counterparts surviving the follow-up period (1.06 mmol/L and 20.6%,
      respectively). Decreasing age-adjusted rates of ischemic stroke mortality were
      observed with increasing %HDL: 14.6, 14.0, and 11.8 per 10,000 person-years in
      the low, middle, and upper tertiles of %HDL, respectively. In multivariate
      analysis, a low concentration of HDL-C appeared to be significantly predictive of
      ischemic stroke mortality. The relative risk associated with a 5% decrease of
      %HDL was 1.18 (95% confidence interval, 1.03 to 1.34). Men at the lower tertile
      of HDL-C levels experienced a 1.32-fold increase of covariate-adjusted ischemic
      stroke mortality risk compared with counterparts at the upper tertile.
      CONCLUSIONS: In this prospective study of middle-aged and elderly men from a
      healthy, working population, we have demonstrated an independent negative
      association between HDL-C and ischemic stroke mortality during a long-term (21
      year) follow-up.

PMID- 8996495
TI  - Associations between carotid atherosclerosis and high factor VIII activity,
      dyslipidemia, and hypertension.
AB  - BACKGROUND AND PURPOSE: A subsample of 147 Chinese subjects from a population
      based study of cardiovascular diseases (Cardiovascular Disease Risk Factor Two
      Township Study) participated in an ancillary study on extracranial carotid color
      duplex ultrasonography that aimed to assess the relations of coagulation factors
      to stroke and carotid atherosclerosis. METHODS: Logistic models were used to
      study the associations between cardiovascular disease risk factors and
      stroke/carotid atherosclerosis, controlling for the effects of age and sex.
      RESULTS: Stroke was significantly associated with hypertension and high values of
      plasma glucose but not with fibrinogen, factor VIIc, or factor VIIIc. Carotid
      plaques identified in this study were mostly mild and moderate. The presence of
      these mild and moderate carotid plaques was significantly associated with high
      values of factor VIII activity, hypercholesterolemia, hypertriglyceridemia, and
      hypertension. The highest tertile of factor VIIIc (> 1.53) was associated with an
      odds ratio of 3.35 for carotid atherosclerosis when compared with the lowest
      tertile (< 1.20). A multiple logistic regression including all significant risk
      factors showed that the degree of association between factor VIIIc and
      atherosclerosis was attenuated to an odds ratio of 2.65 (P = .061). CONCLUSIONS:
      In the present study, the roles of hypertension, hypercholesterolemia, and
      hypertriglyceridemia have been implicated in the pathogenesis of carotid
      atherosclerosis, and roles for hypertension and hyperglycemia in stroke were
      indicated. A positive association between factor VIIIc and carotid
      atherosclerosis in this Chinese population was found. Whether this association is
      independent of the effect of other cardiovascular risk factors awaits further
      study.

PMID- 8996496
TI  - Carotid plaque morphology and clinical events.
AB  - BACKGROUND AND PURPOSE: Studies have suggested that B-mode ultrasonography can be
      used to determine carotid plaque composition and that specific plaque
      characteristics are associated with a worse clinical outcome. However,
      histological studies examining the relationship between carotid plaque morphology
      and clinical outcome have reported conflicting findings. Furthermore, few
      investigators have described plaque morphology in quantifiable terms. This study
      examines the association between the volume of carotid plaque constituents and
      preoperative ischemic neurological symptoms. Constituents examined were chosen
      based on their potential for identification by current diagnostic imaging
      modalities such as ultrasound or MRI. METHODS: Atherosclerotic plaques from 43
      patients undergoing carotid endarterectomy were examined histologically, with
      sections obtained every 0.5 to 1 mm. The lesions were examined for the presence
      and quantity of fibrous intimal tissue, intraplaque hemorrhage, lipid core,
      necrotic plaque core, and calcification. The quantity of each constituent was
      compared in plaques removed from symptomatic patients with those excised from
      asymptomatic individuals. Differences were analyzed with a Kolmogorov-Smirnov
      statistic. RESULTS: There was no difference between plaques removed from
      asymptomatic and symptomatic patients with regard to the presence and volume of
      fibrous intimal tissue, intraplaque hemorrhage, the lipid core, the necrotic
      core, or calcification. CONCLUSIONS: In patients with highly stenotic carotid
      lesions who are undergoing carotid endarterectomy, gross plaque composition is
      similar regardless of preoperative symptom status. Given this similarity, it is
      unlikely that differences in the volume of intraplaque hemorrhage, lipid core,
      necrotic core, or calcification in atherosclerotic carotid plaques explain their
      embolic history.

PMID- 8996497
TI  - A computational model of acute focal cortical lesions.
AB  - BACKGROUND AND PURPOSE: Determining how cerebral cortex adapts to sudden focal
      damage is important for gaining a better understanding of stroke. In this study
      we used a computational model to examine the hypothesis that cortical map
      reorganization after a simulated infarct is critically dependent on perilesion
      excitability and to identify factors that influence the extent of poststroke
      reorganization. METHODS: A previously reported artificial neural network model of
      primary sensorimotor cortex, controlling a simulated arm, was subjected to acute
      focal damage. The perilesion excitability and cortical map reorganization were
      measured over time and compared. RESULTS: Simulated lesions to cortical regions
      with increased perilesion excitability were associated with a remapping of the
      lesioned area into the immediate perilesion cortex, where responsiveness
      increased with time. In contrast, when lesions caused a perilesion zone of
      decreased activity to appear, this zone enlarged and intensified with time, with
      loss of the perilesion map. Increasing the assumed extent of intracortical
      connections produced a wider perilesion zone of inactivity. These effects were
      independent of lesion size. CONCLUSIONS: These simulation results suggest that
      functional cortical reorganization after an ischemic stroke is a two-phase
      process in which perilesion excitability plays a critical role.

PMID- 8996498
TI  - Mapping of motor cortical reorganization after stroke. A brain stimulation study
      with focal magnetic pulses.
AB  - BACKGROUND AND PURPOSE: Focal transcranial magnetic stimulation (TCS) is used for
      noninvasive and painless mapping of the somatotopical organization of the motor
      cortex. TCS mapping of motor cortical output to the abductor digiti minimi (ADM)
      muscle was followed up in monohemispheric stroke patients by evaluating motor
      evoked potentials (MEPs). This approach allowed noninvasive investigation of the
      functional reorganization of hand motor areas. METHODS: Motor maps were
      constructed for 15 subacute stroke patients about 2 months from the ictus by
      recording MEPs from the ADM muscle via focal TCS in the affected hemisphere (AH)
      and unaffected hemisphere (UH) at the beginning of (T1) and after 8 to 10 weeks
      of neurorehabilitation (T2). Barthel Index and Canadian Neurological Scale scores
      were evaluated as well. An age-sex matched group of 15 healthy control subjects
      was enrolled to establish normative data. RESULTS: MEP excitability threshold was
      significantly higher in the AH of stroke patients than in normal subjects and in
      the UH (P < .001); excitability threshold was not significantly different between
      normal subjects and UH. In the AH, MEPs were significantly (P < .001) delayed in
      latency both in T1 and T2, with a significant decrease of the extenuation of
      motor output area to the ADM muscle (P < .05) in T1 versus control group and UH.
      This area was significantly enlarged (P < .05) in T2. Amplitude of MEPs from the
      AH, both at rest and during voluntary contraction, was significantly lower than
      normal in T1 (P < .001); it increased in T2 (P < .01) during relaxation but was
      still smaller than normal during contraction (P < .001). In combination with
      these findings, an improvement of Barthel Index and Canadian Neurological Scale
      scores (P < .001) was observed between T1 and T2 (P < .001). Central conduction
      time was prolonged in stroke patients both in T1 and T2. Changes in the shape of
      motor maps in the AH during follow-up in T2 were either isolated (therefore
      increasing the interhemispheric asymmetry) or also were "mirrored" on the UH.
      CONCLUSIONS: Our neurophysiological data are consistent with the presence of a
      rearrangement of the motor cortical output area and correlate well with an
      improvement of motor performances. These findings confirm the existence in adults
      of a "plasticity" in the central nervous system that is still operating between 2
      and 4 months from the acute ictal episode. The observed neurophysiological
      modifications are significantly correlated with clinical improvement of
      disability and clinical scores.

PMID- 8996499
TI  - Cerebral hemispheric low-flow infarcts in arterial occlusive disease. Lesion
      patterns and angiomorphological conditions.
AB  - BACKGROUND AND PURPOSE: Among the pathogenetic causes of subcortical hemispheric
      infarcts are small-vessel disease, thromboembolic occlusions of small arteries,
      and hemodynamic compromise in low-flow conditions. A topographic classification
      of these infarcts based on CT and MRI can be misleading. METHODS: We evaluated 30
      consecutive patients with presumed supratentorial low-flow infarcts. CT was
      available in all cases, with additional MRI in 14 patients. In all cases the
      occlusion pattern of the extracranial and intracranial arterial system was
      studied in detail with angiography. RESULTS: The dominant lesion patterns seen on
      CT and MRI were multilocal chainlike lesions in 19 and confluent striated lesions
      in 8 cases located in the supraventricular and paraventricular deep white matter.
      In 8 patients subcortical lesions extended into the adjacent cortex. Angiography
      revealed that extracranial occlusive disease (n = 24) or stenosis of the middle
      cerebral artery (n = 6) was always accompanied by impairment of the circle of
      Willis, in either the anterior part (n = 25) and/or the posterior part (n = 16).
      Moreover, leptomeningeal pathways indicative of vascular hemispheric compromise
      were identified in 26 cases. In total, 29 of 30 patients displayed a noncompetent
      circle of Willis. CONCLUSIONS: Low-flow infarcts show typical but not
      pathognomonic lesion patterns on CT and MRI. Definite diagnosis requires
      knowledge of the complex vascular compromise of the extracranial and/or
      intracranial arterial system. A noncompetent circle of Willis should be regarded
      as the additional predisposing condition in hemispheric low-flow infarcts.

PMID- 8996500
TI  - Incomplete brain infarction of reperfused cortex may be quantitated with
      iomazenil.
AB  - BACKGROUND AND PURPOSE: [123I]Iomazenil is a specific radioligand for the central
      benzodiazepine receptor that may be useful as an indicator of the intactness of
      cortical neurons after focal cerebral ischemia. We evaluated the binding of this
      receptor in reperfused cortex among patients with ischemic stroke to detect
      viable neurons in cortex that appeared structurally intact on conventional
      neuroimaging studies. METHODS: Fourteen patients were selected by (1) angiography
      within 24 hours of onset showing embolic occlusion of an intracranial artery, (2)
      cerebral blood flow showing ischemia of moderate severity in 12 cases and
      spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24
      hours in most cases. Thirty reperfused cortical areas that remained structurally
      intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with
      reduced blood flow were selected as regions of interest to estimate receptor
      binding 5 days to 23 months after the stroke. A two-compartment model was used to
      compute the distribution volume (Vd) of iomazenil in relative units, with Vd
      proportional to benzodiazepine receptor concentration. The side-to-side asymmetry
      ratio of Vd was calculated. RESULTS: The mean asymmetry ratio was 0.89 +/- 0.11
      (range, 0.64 to 1.05), 0.50 +/- 0.15 (range, 0.23 to 0.67), and 0.97 +/- 0.05
      (range, 0.90 to 1.04) in reperfused cortex, infarcted cortex, and contralateral
      cerebellum, respectively. Compared with unity, both reperfused cortex and
      infarcted cortex showed significant decrease of Vd (P < .001). Contralateral
      cerebellum showing diaschisis had no reduction of Vd. On MRI, obtained 3 or 6
      months after the stroke, mild cortical atrophy was observed in two reperfused
      areas where the asymmetry ratio was moderately reduced (0.64 and 0.80).
      CONCLUSIONS: The reduction of benzodiazepine receptor concentration in reperfused
      cortex that remained structurally intact is likely to be the result of injury
      involving only a limited number of neurons (ie, incomplete infarction). Our data
      suggest that the degree of viability of ischemic cortex apparently salvaged by
      early reperfusion can be quantified by iomazenil.

PMID- 8996501
TI  - Transcranial Doppler ultrasound battery reliably identifies severe internal
      carotid artery stenosis.
AB  - BACKGROUND AND PURPOSE: There is a clinical imperative for noninvasive tests for
      carotid disease that have high sensitivity. Previous studies have shown that
      transcranial Doppler ultrasound (TCD) can identify intracranial collateral flow
      patterns and other hemodynamic consequences of carotid occlusion. We hypothesized
      that a battery of such TCD findings would have a greater sensitivity than any one
      TCD finding alone and would have clinical utility in identifying carotid disease.
      METHODS: We determined the prevalence of seven TCD findings in patients with
      various degrees of carotid stenosis as measured by a blinded observer on 138
      cerebral angiograms. We further determined the sensitivity and specificity of any
      one finding or any single abnormality in the TCD battery (the combination of all
      seven findings) for identifying severe (> or = 70%) carotid stenosis by
      angiography. RESULTS: The following four individual TCD findings were associated
      (P < .001) with > or = 70% carotid stenosis on cerebral angiography: ophthalmic
      and anterior cerebral artery flow reversal and low middle cerebral artery flow
      acceleration and pulsatility. The presence of any single abnormality in the TCD
      battery had a similar association (P < .001) with > or = 70% carotid stenosis.
      The individual TCD findings had sensitivities of 3% to 83% and specificities of
      60% to 100% for identifying > or = 70% carotid stenosis. The TCD battery had a
      sensitivity of 95% and specificity of 42% for identifying > or = 70% carotid
      stenosis. CONCLUSIONS: A battery of TCD findings that can be routinely measured
      reliably identified patients with > or = 70% angiographic internal carotid artery
      stenosis with high sensitivity.

PMID- 8996502
TI  - Length of hospital stay and discharge delays in stroke patients.
AB  - BACKGROUND AND PURPOSE: In The Netherlands, many stroke patients stay in the
      hospital for some time merely waiting for discharge placement. This indicates an
      inefficient use of hospital resources, as well as a possible deficiency in the
      quality of care, because hospitals are not adequately equipped to care for these
      patients. In this study, we tried to quantify this "waiting problem." METHODS:
      Six hospitals and 29 neurologists participated in this prospective study. The
      neurologists were asked during weekly interviews to specify for 154 patients the
      reason for retention in the hospital on a day-to-day basis. The reasons were
      noted on a list specified by the authors in advance. RESULTS: The mean length of
      hospital stay was 28 days. On average, there were "hard" medical reasons for 15
      days (54%) and "soft" medical reasons for 3 days (10%), whereas the remaining 10
      days (36%) were explained by nonmedical reasons (most frequently, waiting for
      placement in a nursing home). CONCLUSIONS: The length of hospital stay for stroke
      patients in The Netherlands can be reduced considerably without compromising the
      quality of care. This might be realized by increasing the capacity of long-term
      care facilities, improving the efficiency of the discharge procedures, or
      creating "stroke services."

PMID- 8996503
TI  - Ventricular dilatation in experimental intraventricular hemorrhage in pigs.
      Characterization of cerebrospinal fluid dynamics and the effects of fibrinolytic
      treatment.
AB  - BACKGROUND AND PURPOSE: Hemorrhagic ventricular dilatation (HVD) is a prominent
      feature of human intraventricular hemorrhage (IVH) and a strong indicator for
      poor outcome. We developed an IVH model to define the mechanisms responsible for
      HVD and to test the efficacy of intraventricular administration of tissue
      plasminogen activator (TPA) in the treatment of HVD. METHODS: Isolated IVH was
      produced in pigs by injecting 10 mL of blood simultaneously with thrombin into
      the right lateral ventricle. The treatment group received 1.5 mg of TPA after
      induction of IVH. Intraventricular blood volume and the volume of the lateral
      ventricles were assessed by CT after 90 minutes, 7 days, and 42 days.
      Intracranial pressure, the pressure-volume index, and the resistance to outflow
      of cerebrospinal fluid (R(out)) were measured 30 minutes and 7 days after IVH.
      RESULTS: After IVH, the volume of the lateral ventricles increased from 1.98 +/-
      0.69 to 6.43 +/- 1.23 mL (P < .001). There was a linear relationship between
      ventricular and clot volume (P = .014). Initially, R(out) increased from 24.34 +/
      7.13 to 63.56 +/- 64.91 mm Hg/mL per minute (P < .001). After 7 days,
      restoration of normal cerebrospinal fluid circulation occurred, but the
      ventricles were still significantly enlarged (5.24 +/- 1.76 mL, P < .001) and
      filled with blood. Within 6 weeks, ventricular volume had returned to normal
      values, paralleled by complete clot resolution. Intraventricular administration
      of TPA significantly accelerated clot clearance and restoration of normal
      ventricle volume. CONCLUSIONS: These results suggest that intraventricular
      bleeding may cause impairment of cerebrospinal fluid circulation but that the
      mass effect of clots distending the ventricle walls is the most important
      mechanism responsible for HVD. This model closely imitates several prominent
      features of human IVH and may therefore be a useful tool for preclinical
      assessment of the efficacy and safety of treatment with TPA.

PMID- 8996504
TI  - Hyperglycemia and the vascular effects of cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: A well-demarcated infarct was observed after 4 hours of
      rat middle cerebral artery (MCA) occlusion with xylazine/ketamine but not
      pentobarbital or isoflurane anesthesia. This study examined whether this
      reflected vascular changes and, because xylazine induces hyperglycemia, whether
      glucose could cause similar vascular effects in cerebral ischemia. METHODS: To
      examine the effects of anesthetics, rats were anesthetized for thread occlusion
      of the MCA with either xylazine/ketamine, pentobarbital, or isoflurane. To
      evaluate the effects of glycemia, acute hyperglycemia was induced by glucose
      injection. In both experiments, cerebral plasma volume (CPV) was determined using
      3H-inulin after 4 hours of permanent occlusion, and cerebral blood flow was
      measured using [14C]iodoantipyrine following 2 hours of reperfusion after 2 or 4
      hours of occlusion. The presence of cerebral hemorrhage after reperfusion was
      checked macroscopically and infarct volume with 2,3,5-triphenyltetrazolium
      staining. RESULTS: The ischemic CPV was about 50% of the contralateral values
      with xylazine/ketamine but not with the other anesthetics. On reperfusion,
      ischemic cerebral blood flow with xylazine/ketamine anesthesia was approximately
      half that with pentobarbital. Use of xylazine/ketamine also resulted in more
      frequent hemorrhagic infarcts and a larger infarct volume. Induced hyperglycemia
      resulted in a CPV decrease in the ischemic compared with nonischemic tissue (4.0
      +/- 0.5 versus 7.4 +/- 0.2 microL/g; P < .001). Hyperglycemia also caused poor
      reperfusion and increased the occurrence of hemorrhagic infarction
      (hyperglycemia, 15 of 20; normoglycemia, 1 of 11; P < .01). CONCLUSIONS:
      Hyperglycemia induces marked cerebrovascular changes, both during ischemia and
      during reperfusion, that may exacerbate tissue damage. Change in CPV during
      ischemia may be a useful clinical indicator in predicting poor hemodynamic
      recovery and occurrence of hemorrhagic infarction after reperfusion therapy.

PMID- 8996505
TI  - Interleukin-1 receptor and receptor antagonist gene expression after focal stroke
      in rats.
AB  - BACKGROUND AND PURPOSE: The expression of interleukin-1 beta (IL-1 beta) is
      upregulated after focal brain ischemia, and previous work has demonstrated its
      involvement in ischemic injury. The IL-1 receptor antagonist (IL-1ra), a natural
      competitive antagonist of IL-1 receptors (IL-1Rs), has been demonstrated to play
      a role in attenuating brain ischemic injury. To hypothesize the involvement of
      the IL-1 system in ischemic injury, we examined other IL-1 components, including
      IL-1ra, IL-1RI, and IL-1RII for their mRNA expression after focal stroke.
      METHODS: Quantitative reverse transcription and polymerase chain reaction (RT
      PCR) technique was used to examine the mRNA expression profile of IL-1ra and two
      IL-1R isoforms in a temporal fashion (n = 4 for each time point) after permanent
      occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive
      rats. IL-1ra and IL-1R mRNA expression was confirmed by Northern blot analysis
      using poly(A) RNA isolated after 2 and 12 hours of MCAO. RESULTS: Very low levels
      of IL-1ra mRNA were detected in sham-operated or nonischemic cortex. IL-1ra mRNA
      in ischemic cortex was greatly increased at 12 hours (16.5-fold increase over
      sham samples, P < .001) and remained elevated for up to 5 days (17.2-fold
      increase, P < .01) after MCAO. IL-1RI mRNA was relatively highly expressed in
      normal cortex and was further elevated late after ischemic injury (3.3-fold
      increase at day 5, P < .001). In contrast, the low basal expression of IL-1RII
      mRNA was remarkably elevated at 6 hours (5.3-fold increase, P < .05), reaching
      peak levels 12 hours (10.3-fold increase, P < .001) after MCAO. CONCLUSIONS:
      Differential expression of IL-1 beta, IL-1ra, IL-1RI, and IL-1RII mRNAs after
      focal stroke may suggest a distinct role(s) for each component of the IL-1 system
      in ischemic injury. The data also stress the importance of evaluating all the
      components of a given cytokine system (eg, agonist, receptors, and natural
      antagonist) after focal stroke.

PMID- 8996506
TI  - Subtle neuronal death in striatum after short forebrain ischemia in rats detected
      by in situ end-labeling for DNA damage.
AB  - BACKGROUND AND PURPOSE: Neuronal cell death after global brain ischemia occurs
      predominantly by necrosis, whereas only a minor fraction of cell death may occur
      through apoptosis. Brief or moderate insults are thought to facilitate apoptosis,
      which is associated with DNA fragmentation. After 10 minutes of four-vessel
      occlusion in rats, conventional neuropathological analysis shows neuronal cell
      death in hippocampal CA1 but not in the striatum. Thus, we compared hippocampus
      and striatum for occurrence of cells with DNA fragmentation. METHODS: A brief
      insult of 10 minutes of forebrain ischemia was induced in rats using four-vessel
      occlusion, and groups of brains were studied at 1, 3, 6, and 12 hours and at 1,
      3, and 7 days after ischemia. In situ end-labeling (ISEL) was used to detect
      neurons undergoing DNA fragmentation. The hippocampal CA1 area was compared with
      the striatum. Conventional staining and immunohistochemical markers served to
      exclude ischemic neuronal cell death in the striatum. RESULTS: Hippocampal CA1
      neurons were ISEL-positive by 3 days after ischemia. In contrast, positive cells
      became evident in the striatum between 3 hours to 3 days after ischemia. The ISEL
      positive cells were scattered throughout the striatum with a preference for the
      dorsomedial areas and accounted for about 0.2% of the neurons per striatal area
      at 1 day. Conventional staining and immunohistochemical markers failed to reveal
      areas of overt cell damage in the striatum. CONCLUSIONS: The scattered cell
      damage in the striatum after brief forebrain ischemia suggests the occurrence of
      an apoptotic process. The striatum therefore may be prone to subtle cell death
      due to metabolic insults.

PMID- 8996507
TI  - Age-related changes in response of brain stem vessels to opening of ATP-sensitive
      potassium channels.
AB  - BACKGROUND AND PURPOSE: This study was designed to determine regional differences
      and age-related changes in the contribution of ATP-sensitive potassium (KATP)
      channels to vasodilator responses in the brain stem circulation in vivo. METHODS:
      Changes in diameter of the basilar artery (baseline diameter, 270 +/- 5 microns
      [mean +/- SEM]), its large branch (112 +/- 5 microns), and its small branch (49
      +/- 2 microns) in response to KATP channel openers levcromakalim and Y-26763 were
      measured through a cranial window in anesthetized adult (4 to 6 months) and aged
      (24 to 26 months) Sprague-Dawley rats. RESULTS: Topical application of
      levcromakalim and Y-26763 produced concentration-dependent vasodilation that was
      similar among the three vessel groups in adult rats. In aged rats, dilator
      responses of the branches, but not of the basilar artery, to the KATP channel
      openers were smaller than those in adult rats (P < .05). Glibenclamide, a
      selective KATP channel blocker, almost abolished this vasodilation in both groups
      of rats. Vasodilator responses to sodium nitroprusside were preserved in aged
      rats. CONCLUSIONS: In adult rats, there is no regional heterogeneity in
      vasodilator response to KATP channel openers in the brain stem circulation in
      vivo. In aged rats, although KATP channels are also functional in the brain stem
      circulation, dilator response of the microvessels but not of the large arteries
      to direct activation of KATP channels is impaired.

PMID- 8996508
TI  - Reperfusion decreases myogenic reactivity and alters middle cerebral artery
      function after focal cerebral ischemia in rats.
AB  - BACKGROUND AND PURPOSE: After focal cerebral ischemia, the function of cerebral
      arteries is critical to maintain cerebrovascular resistance and minimize damage
      to ischemic brain regions during reperfusion. In this study we examined the
      contractile function of isolated and pressurized middle cerebral arteries (MCAs)
      after 2 hours of occlusion with either 1 to 2 minutes or 24 hours of reperfusion
      using the intraluminal suture model of transient focal ischemia in rats. METHODS:
      MCAs were dissected after 2 hours of occlusion with either 1 to 2 minutes (OCC, n
      = 8) or 24 hours (RPF, n = 5) of reperfusion and compared with those of controls
      that did not have surgery (n = 5). Isolated MCAs were mounted on two glass
      cannulas in an arteriograph chamber that allowed control over transmural pressure
      (TMP) and measurement of lumen diameter. Responses to changes in TMP (including
      myogenic reactivity, basal tone, and passive distensibility) and sensitivity to
      serotonin and acetylcholine were compared. RESULTS: Increasing TMP from 25 to 75
      mm Hg caused vasoconstriction and development of tone that was similar in control
      and OCC arteries: percent tone was 33 +/- 5% versus 25 +/- 7% (P > .05). In
      contrast, tone was severely diminished in RPF MCAs after 24 hours of reperfusion:
      percent tone = 8 +/- 4% (P < .01). Sensitivity to serotonin was reduced in OCC
      arteries, increasing the EC50 value from 0.04 +/- 0.1 to 0.11 +/- 0.02 mumol/L (P
      < .05); after 24 hours of reperfusion, sensitivity of RPF MCAs was similar to
      control. Vasodilation to 10.0 mumol/L acetylcholine was significantly impaired
      only in RPF arteries: percent increased lumen diameter was 19 +/- 3% (control)
      and 13 +/- 4% (OCC, P > .05) versus 9 +/- 2% (RPF, P < .01). Passively, OCC MCAs
      were more distensible, which was reversed after 24 hours of reperfusion; RPF
      vessels had distensibility similar to that of control arteries but thicker
      arterial walls. CONCLUSIONS: Abnormal structure and function of MCAs occur after
      2 hours of ischemia, with diminished myogenic reactivity and tone associated with
      longer reperfusion.

PMID- 8996509
TI  - Mechanisms of adrenomedullin-induced dilatation of cerebral arterioles.
AB  - BACKGROUND AND PURPOSE: Adrenomedullin is a recently discovered vasoactive
      peptide that is structurally related to calcitonin gene-related peptide (CGRP).
      Adrenomedullin is produced by vascular endothelium and smooth muscle and is
      present in the brain. The goals of this study were to determine (1) whether
      adrenomedullin produces dilatation of cerebral arterioles and whether this effect
      is mediated by activation of CGRP receptors and (2) whether vasodilatation to
      adrenomedullin was mediated by K+ channels. METHODS: Diameter of cerebral
      arterioles (mean +/- SE baseline, 46 +/- 1 microns) was measured using a closed
      cranial window in anesthetized rats. RESULTS: Application of rat adrenomedullin
      (10(-7) and 10(-6) mol/L) increased vessel diameter by 16 +/- 3% and 45 +/- 8% (n
      = 5), respectively. Vasodilator responses to repeated application of
      adrenomedullin were reproducible. Pretreatment of cerebral arterioles with the
      specific CGRP1 receptor antagonist CGRP-(8-37) (5 x 10(-7) mol/L) selectively
      inhibited the vasodilator responses to adrenomedullin without inhibiting
      responses to ADP (10(-5) to 10(-3) mol/L). Responses to adrenomedullin (10(-7)
      and 10(-6) mol/L) were 14 +/- 1% and 40 +/- 3% before and 2 +/- 2% and 6 +/- 1%
      after CGRP-(8-37), respectively (P < .01). Glibenclamide (10(-6) mol/L), an
      inhibitor of ATP-sensitive K+ channels, reduced the responses to adrenomedullin
      without attenuating responses to ADP. Responses to adrenomedullin were 19 +/- 4%
      and 35 +/- 6% before and 6 +/- 3% and 19 +/- 5% after glibenclamide, respectively
      (P < .05). Iberiotoxin (10(-7) mol/L), an inhibitor of calcium-dependent K+
      channels, also significantly attenuated responses to adrenomedullin and did not
      inhibit vasodilatation to papaverine. Responses to adrenomedullin were 16 +/- 2%
      and 55 +/- 8% before and 12 +/- 4% and 26 +/- 3% after iberiotoxin, respectively
      (P < .01 for 10(-6) mol/L adrenomedullin). CONCLUSIONS: Adrenomedullin produces
      substantial dilatation of cerebral arterioles in vivo, and the response is
      mediated in large part by activation of CGRP1 receptors. Cerebral vasodilatation
      to adrenomedullin appears to be dependent on activation of K+ channels.

PMID- 8996510
TI  - Tetrahydrobiopterin, a cofactor for nitric oxide synthase, produces endothelium
      dependent dilation of mouse pial arterioles.
AB  - BACKGROUND AND PURPOSE: Tetrahydrobiopterin (THBP) is an essential cofactor for
      nitric oxide synthase (NOS), which is responsible for the synthesis of the
      endothelium-derived relaxing factor (EDRF) responsible for mediating the
      vasorelaxation produced by acetylcholine (ACh). Previous publications suggest
      that EDRFACh is continuously synthesized and released from the endothelium of
      mouse pial arterioles. If so, then one may predict that addition of THBP will
      increase the local production of EDRFACh and produce an endothelium-dependent
      relaxation that can be blocked by application of a known inhibitor of NOS. This
      study tests the prediction. METHODS: The pial vessels were observed at a
      continuously suffused craniotomy site by means of intravital television
      microscopy. The effects of topically applied THBP on diameter were monitored
      before and after endothelial damage and before and after local treatment with the
      NOS inhibitor N-guanidino-L-monomethyl arginine (LNMMA). The endothelial damage
      was produced by a helium-neon laser in the presence of Evans blue dye. RESULTS: A
      dose-dependent relaxation was produced by 10(-3) and 10(-2) mol/L THBP. The
      response was virtually eliminated by endothelial injury. LNMMA 10(-6) mol/L also
      greatly inhibited dilation. CONCLUSIONS: The data are consistent with all reports
      that THBP is a cofactor for constitutive endothelial NOS. The data are consonant
      with previous results suggesting that EDRFACh is continually synthesized and
      released. It appears that THBP increases this synthesis and consequently the
      local level of released EDRFACh. The continuous spontaneous synthesis/release of
      EDRFACh modulates basal tone and, according to other studies, helps maintain a
      platelet-free endothelial surface.

PMID- 8996511
TI  - Endothelin production links superoxide generation to altered opioid-induced pial
      artery vasodilation after brain injury in pigs.
AB  - BACKGROUND AND PURPOSE: Traumatic brain injury conveys significant morbidity and
      mortality to infants and children. In the newborn pig, opioids contribute to pial
      artery vasconstriction after fluid percussion injury (FPI). FPI attenuates
      vasodilation and cGMP production by methionine enkephalin (Met) and leucine
      enkephalin (Leu) and reverse dynorphin (Dyn) from a dilator to a constrictor.
      Superoxide anion (O2-) production contributes to altered cerebral hemodynamics
      after FPI, and O2- scavengers partially restore decreased dilator responses after
      FPI. Endothelin-1 (ET-1), a purported mediator of cerebral vasospasm, has been
      suggested to alter nitric oxide function and cGMP concentration. The present
      study was designed to determine the contribution of ET-1 to altered opioid
      induced dilation after FPI and the role of O2- in such altered responses.
      METHODS: Injury of moderate severity (1.9 to 2.3 atm) was produced by the lateral
      FPI technique in anesthetized newborn pigs equipped with a closed cranial window.
      Superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was
      determined as an index of O2- generation. RESULTS: FPI increased cerebrospinal
      fluid ET-1 from 20 +/- 2 to 93 +/- 6 pg/mL (approximately 10(-10) mol/L). Topical
      ET-1 (10(-10) mol/L) increased SOD-inhibitable NBT reduction from 1 +/- 1 to 16
      +/- 3 pmol/mm2, similar to previously reported NBT reduction after FPI (14 +/- 2
      pmol/mm2). BQ123 (10(-6) mol/L), an ET-1 antagonist, blunted the NBT reduction
      observed after FPI (4 +/- 1 pmol/mm2). Met produced pial vasodilation that was
      attenuated by FPI and partially restored by BQ123 pretreatment (7 +/- 1%, 11 +/-
      1%, and 17 +/- 1% versus 3 +/- 1%, 6 +/- 1%, and 9 +/- 2% versus 5 +/- 1%, 9 +/-
      1%, and 14 +/- 2% for 10(-10), 10(-8), and 10(-6) mol/L Met during control
      conditions, after FPI, and after FPI pretreated with BQ123, respectively). Met
      induced dilation was associated with increased cerebrospinal fluid cGMP, and
      these biochemical changes were likewise blunted by FPI and partially restored by
      BQ123 (357 +/- 12, 455 +/- 15, 500 +/- 19, and 632 +/- 11 versus 264 +/- 4, 267
      +/- 4, 295 +/- 12, and 305 +/- 15 versus 309 +/- 19, 432 +/- 11, 529 +/- 10, and
      593 +/- 4 pg/mL for resting conditions, 10(-10), 10(-8), and 10(-6) mol/L Met
      during control conditions, after FPI, and after FPI pretreated with BQ123,
      respectively). Similar partial restoration of vascular and biochemical parameters
      was observed for Leu and Dyn. CONCLUSIONS: These data show that ET-1, in
      concentrations similar to that present in cerebrospinal fluid after FPI,
      increases O2- production. These data also indicate the opioid-induced
      vasodilation and cGMP production are partially restored after FPI by ET-1
      receptor blockade. These data suggest that ET-1 contributes to altered cerebral
      hemodynamics after FPI, at least in part, through elevated O2- production.

PMID- 8996512
TI  - Parallel antioxidant and antiexcitotoxic therapy improves outcome after
      incomplete global cerebral ischemia in dogs.
AB  - BACKGROUND AND PURPOSE: We have previously shown that incomplete global cerebral
      ischemia complicated by dense acidosis produces a profound secondary
      deterioration of energy metabolism and cerebral blood flow. Antioxidant treatment
      only partially averts this deterioration, suggesting that parallel or sequential
      mechanisms are involved in cerebral ischemic injury. We tested the hypothesis
      that a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist GPI 3000
      (GPI) ameliorates metabolic injury and that the effectiveness of the iron
      chelator and antioxidant deferoxamine (DFO) is augmented by combined therapy with
      GPI after incomplete global cerebral ischemia. METHODS: Anesthetized dogs were
      treated with 30 minutes of global incomplete cerebral ischemia. Preischemic
      plasma glucose was raised to approximately 500 mg/dL to exaggerate lactic
      acidosis. Brain ATP, phosphocreatine, and pH were measured by 31P MR spectroscopy
      for 180 minutes of reperfusion. Neurophysiological outcomes were assessed by
      evoked potential monitoring. Five groups were treated with either saline; 75
      mg/kg DFO preischemia plus 75 mg/kg at reperfusion onset, followed by 27.5 mg/kg
      per hour for the remainder of reperfusion (DFO group); 25 mg/kg GPI pretreatment,
      followed by 5 mg/kg per hour (GPI-pre group); 25 mg/kg GPI at reperfusion,
      followed by 5 mg/kg per hour (GPI-post group); or DFO and GPI-pre at the same
      doses (Combined group). RESULTS: Ischemic cerebral blood flow (microspheres: 5 to
      8 mL/min per 100 g) was similar among the groups. End-ischemic pHi was also
      similar; 5.9 in saline, 6.1 in DFO, 6.2 in GPI-pre, 6.2 in Combined, and 6.1 in
      GPI-post groups. Progressive hypoperfusion was observed in all groups except
      Combined during reperfusion. Metabolic recovery was improved relative to saline
      in all drug-treated groups. Phosphocreatine recovery was improved in Combined
      compared with DFO and GPI-pre groups. Somatosensory evoked potential recovery was
      not observed in the saline group and incomplete in all treatment groups. At 60
      and 90 minutes of reperfusion, DFO, GPI-pre, and Combined groups demonstrated
      improved recovery relative to the saline group. CONCLUSIONS: Pretreatment and
      posttreatment with GPI ameliorated postischemic metabolic failure, suggesting
      that NMDA-mediated mechanisms are more important in global cerebral ischemia
      complicated by dense, acidosis than early studies indicated. Combined treatment
      with GPI and DFO improved cerebral blood flow during reperfusion and one
      indicator of energy recovery. These data support the hypothesis that parallel
      therapy aimed at antioxidant and antiexcitotoxic mechanisms of ischemic brain
      injury augment recovery compared with the individual agents.

PMID- 8996513
TI  - Extracellular potassium in a neocortical core area after transient focal
      ischemia.
AB  - BACKGROUND AND PURPOSE: Occlusion of the middle cerebral artery (MCAO) results in
      bioenergetic failure in the densely ischemic core areas. During reperfusion,
      transient recovery of the bioenergetic state is followed by secondary
      deterioration. In this study, we recorded the extracellular potassium
      concentrations in the cortical core during 2 hours of MCAO, as well as during
      recovery. One group of animals with recirculation periods of 6 to 8 hours was
      given the free radical spin trap alpha-phenyl-N-tert-butyl nitrone (PBN).
      METHODS: The experiments were performed on adult male Wistar rats (305 to 335 g).
      The right MCA was occluded by an intraluminal filament technique. For [K+]e
      measurements a craniotomy was made over the right cortex, and an ion-sensitive
      microelectrode was lowered into the ischemic focus. Recording of [K+]e was
      continued for 2 hours. After 48 hours of reperfusion, infarction size was
      estimated with 2,3,5-triphenyltetrazolium chloride. RESULTS: During MCA
      occlusion, [K+]e rose to approximately 60 mmol/L. However, several animals showed
      transient (and partial) periods of repolarization accompanied by a decrease in
      [K+]e. Immediately on reperfusion, the [K+]e started to recover and reached
      baseline levels (2.5 mmol/L) within 3 to 5 minutes. During the first 6 hours of
      recovery, [K+]e was stable at about 2.5 mmol/L, but after this period a moderate
      increase in the [K+]e was observed. This was not observed in animals injected
      with PBN 1 hour after reperfusion. CONCLUSIONS: The data suggest that delayed
      cell membrane dysfunction, as reflected in a rise in [K+]e, occurs after about 6
      hours of reperfusion and that treatment with PBN in a single dose ameliorates or
      delays such deterioration of plasma membrane function.

PMID- 8996514
TI  - Large cerebral infarction during praziquantel therapy in neurocysticercosis.
AB  - BACKGROUND: Large cerebral infarction is a rare complication of
      neurocysticercosis. Endarteritis by inflammation of the leptomeninges is known to
      be its cause. CASE DESCRIPTION: A 59-year-old man with known neurocysticercosis
      developed a large cerebral infarction during praziquantel therapy. A follow-up
      MRI obtained immediately after his cerebral infarction demonstrated notable
      decrease in the size of the cysts and more prominent enhancement around the
      peripheral margins of the cysts and the major vessels in comparison with the
      initial MRI. Cerebral angiography disclosed occlusions and narrowing of both
      internal carotid arteries at the supraclinoid portions, where multiple cysts were
      found on the MRI. CONCLUSIONS: Findings in our patient strongly suggest that a
      secondary inflammation reaction caused by the destruction of the cysts might have
      enhanced the process of endarteritis. The possible deleterious effects of
      praziquantel therapy should be considered in the treatment of patients with
      subarachnoid cysticerci.

PMID- 8996515
TI  - When is thrombolysis justified in patients with acute ischemic stroke? A
      bioethical perspective.
AB  - BACKGROUND: Thrombolytic therapy for acute ischemic stroke raises several
      unsettled bioethical issues related to risk versus benefit. Excluding the
      National Institutes of Neurological Disorders and Stroke (NINDS) rt-PA trial, the
      risk of intracerebral hemorrhage averages 10.3%, and there is a 44% increase in
      the odds of death among fibrinolysis-treated patients. Some investigators have
      suggested that as yet unidentified subgroups may benefit despite an increased
      early risk of hemorrhage and death, while others have warned that the widespread
      use of thrombolysis cannot currently be recommended despite recent Food and Drug
      Administration approval. The NINDS rt-PA trial showed a net benefit, but the
      relative risk to benefit ratio in individual patients is uncertain because of
      incomplete subgroup analysis. We explore these and related issues by applying the
      bioethical principle of justification to the selection of stroke patients for
      thrombolysis. SUMMARY OF COMMENT: Justification of a therapy rests on the
      criteria of safety, efficacy (net benefit under ideal conditions), effectiveness
      (net benefit under routine conditions), efficiency (cost-effectiveness or cost
      benefit), and outcome (proportionality and informed consent). The ethical
      principal of proportionality states that positive outcomes must be proportional
      to negative outcomes; only the NINDS trial sets equipoise between risk and
      benefit. The relative risk to benefit ratio and cost-effectiveness of
      thrombolysis will likely vary among treating physicians and patient subgroups.
      Although some potential selection factors such as early CT changes, National
      Institutes of Health Stroke Scale score > 22, and age > 77 years have been
      identified, it is not yet possible to predict response to treatment in individual
      patients. The effectiveness of thrombolysis outside of a clinical trial has not
      yet been demonstrated, and it is not clear that thrombolysis is cost-effective
      for all potential patient subgroups. CONCLUSIONS: No stroke thrombolysis regimen
      has met all five justification criteria. Proportional outcome standards that take
      into account patient preferences must be established. The risk to benefit ratio
      of thrombolysis in patient subgroups requires clarification and should
      incorporate cost-efficiency analyses. These issues should be kept in mind when
      considering thrombolysis therapy in patients with acute ischemic stroke and when
      designing clinical trials.

PMID- 8996516
TI  - Limited sensitivity of transcranial color-coded duplex sonography in the
      assessment of the posterior communicating artery.

PMID- 8996518
TI  - Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1
      piperidino]-1-piperidino)-carbonyloxy-camptothecin against pediatric and adult
      central nervous system tumor xenografts.
AB  - Therapy of patients with malignant central nervous system tumors is frequently
      unsuccessful, reflecting limitations of current surgical, radiotherapeutic, and
      pharmacotherapeutic treatments. The camptothecin derivative irinotecan (CPT-11)
      has been shown to possess antitumor activity in phase II trials for patients with
      carcinoma of the lung, cervix, ovary, colon, or rectum and for patients with non
      Hodgkin's lymphoma. The current study was designed to test the efficacy of the
      drug against a panel of human tumor xenografts derived from adult and pediatric
      central nervous system malignancies. Tumors included childhood high-grade gliomas
      (D-212 MG, D-456 MG), adult high-grade gliomas (D-54 MG, D-245 MG),
      medulloblastomas (D341 Med, D487 Med), ependymomas (D528 EP, D612 EP), and a
      rhabdomyosarcoma (TE-671), as well as sublines with demonstrated resistance to
      busulfan (D-456 MG (BR)), cyclophosphamide (TE-671 CR), procarbazine (D-245 MG
      (PR)) or melphalan (TE-671 MR), growing subcutaneously and intracranially in
      athymic nude mice. In replicate experiments, CPT-11 was given at a dosage of 40
      mg/kg per dose via intraperitoneal injection in 10% dimethylsulfoxide on days 1-5
      and 8-12, which is the dosage lethal to 10% of treated animals. CPT-11 produced
      statistically significant (P < 0.001) growth delays in all subcutaneous
      xenografts tested, including those resistant to busulfan, cyclophosphamide,
      procarbazine, and melphalan, with growth delays ranging from 21.3 days in D487
      Med to 90+ days in several tumor lines. Further, tumor regression was evident in
      every treated animal bearing a subcutaneous tumor, with some xenografts yielding
      complete tumor regression. Statistically significant (P < 0.001) increases in
      survival were demonstrated in the two intracranial xenografts-D341 EP (73.0%
      increase) and D-456 MG (114.2% increase)-treated with CPT-11. These studies
      demonstrate that, of over 40 drugs evaluated in this laboratory, CPT-11 is the
      most active against central nervous system xenografts and should be advanced to
      clinical trial as soon as possible.

PMID- 8996517
TI  - L-amino acid oxidase (LOX) modulation of melphalan activity against intracranial
      glioma.
AB  - These studies evaluated the efficacy of sequential pretreatment with L-amino acid
      oxidase (LOX) and LOX antiserum in the modulation of melphalan activity against
      intracranial glioma in athymic nude mice. LOX produced statistically significant
      (P < 0.01) depletion of the large neutral amino acids isoleucine, leucine,
      methionine, phenylalanine, tyrosine, and valine in murine plasma at doses of 100
      and 200 micrograms administered intravenously. Polyclonal anti-LOX antibody was
      successfully produced in mice, rabbits, and goats subsequent to immunization with
      LOX. Staphylococcal protein A-purified rabbit anti-LOX serum inhibited
      approximately 50% of LOX activity in vitro relative to control samples. This
      antiserum was used in vivo to inactivate LOX after it had depleted the large
      neutral amino acids, thereby preventing LOX-mediated catabolism of melphalan.
      Inoculation of three mice with rabbit anti-LOX serum after the treatment with LOX
      (100 micrograms) reduced LOX activity by 100%, 89%, and 100% at 6 h compared with
      reductions of 80%, 59%, and 52% over the same period in animals receiving LOX
      alone. In three separate studies using groups of eight to ten mice bearing
      intracranial human glioma xenografts, pretreatment with LOX followed by anti-LOX
      serum increased the antitumor activity of melphalan as compared with treatments
      with melphalan plus LOX, melphalan plus anti-LOX serum, or melphalan alone.

PMID- 8996519
TI  - Topoisomerase II alpha content and topoisomerase II catalytic activity cannot
      explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell
      lines.
AB  - PURPOSE: Topoisomerase II alpha content, topoisomerase II catalytic activity and
      drug sensitivities to the topoisomerase II inhibitors, doxorubicin and etoposide,
      were examined in a panel of 14 unselected human lung cancer cell lines in order
      to determine the relationship between topoisomerase II and drug sensitivities to
      the topoisomerase II inhibitors. METHODS: Drug sensitivities were determined
      using a microculture tetrazolium assay. The topoisomerase II alpha levels were
      determined by Western blot analysis and the topoisomerase II catalytic activity
      was determined using a decatenation assay of kinetoplast DNA, using nuclear
      protein from cells of each cell line. RESULTS: Drug sensitivity tests revealed
      that small-cell lung cancer (SCLC) cell lines were more sensitive to drugs than
      non-small-cell lung cancer (NSCLC) cell lines. The relative topoisomerase II
      alpha levels and relative topoisomerase II catalytic activity from SCLC cell
      lines (mean +/- SD 0.89 +/- 0.54 and 5.3 +/- 3.4, respectively) were slightly
      higher than those from NSCLC cell lines (0.78 +/- 0.56 and 4.0 +/- 2.8,
      respectively), but the differences were not statistically significant, and not
      sufficient to account for the variation in drug sensitivities. Moreover, no clear
      association was observed between the topoisomerase II alpha levels or the
      topoisomerase II catalytic activity and drug sensitivities in the cell lines
      studied. CONCLUSIONS: These findings suggest that the difference in drug
      sensitivities to doxorubicin and etoposide in human lung cancer cell lines might
      not be explainable by the topoisomerase II alpha levels and topoisomerase II
      catalytic activity. Moreover, our results suggest that the topoisomerase II alpha
      levels and topoisomerase II catalytic activity may play a minor role in the
      determination of clinical drug resistance of human lung cancers.

PMID- 8996520
TI  - Combination effects of cisplatin, vinorelbine and irinotecan in non-small-cell
      lung cancer cell lines in vitro.
AB  - PURPOSE: Isobologram analysis has been widely used for evaluating the combined
      effect of two antitumor drugs in vitro as a pre-clinical screening test. In this
      study, we tried to extend two-dimensional isobologram analysis to three
      dimensions for evaluating the effects of a three-drug combination. METHODS: We
      selected three anticancer agents, cisplatin, vinorelbine and irinotecan. Each of
      them has been classified as having good single-agent activity against non-small
      cell lung cancer (NSCLC). Human NSCLC cell lines (EBC-1, PC-3, RERF-LC-MS) were
      incubated for 4 days in the presence of the three drugs and cytotoxic activities
      were determined by a tetrazolium-based colorimetric assay (MTT assay). The data
      were analyzed by three dimensional isobologram analysis. RESULTS: The effects of
      the three drugs were additive against EBC-1 (a squamous cell carcinoma cell
      line), subadditive against PC-3 (an adenocarcinoma cell line) and from
      subadditive to supraadditive against RERF-LC-MS (an adenocarcinoma cell line).
      CONCLUSIONS: Our findings suggest that the effects of cisplatin, vinorelbine and
      irinotecan in combination are additive against NSCLC in vitro. These results
      encourage clinical trials of the three agents in combination chemotherapy for the
      treatment of NSCLC.

PMID- 8996521
TI  - Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral
      tegafur, in experimental tumor models in rats.
AB  - S-1, a new oral antitumor agent, is composed of 1-(2-tetrahydrofuryl)-5
      fluorouracil (Tegafur, FT), 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium
      oxonate (Oxo) in a molar ratio of 1:0.4:1. FT which is a masked compound of 5
      fluorouracil (5-FU) acts as an effector, while both CDHP and Oxo which do not
      have antitumor activity themselves act as modulators. In this study, the
      antitumor activity and intestinal toxicity of S-1 were investigated using
      experimental tumor models in rats, and compared with those of other oral
      fluoropyrimidines, namely 5-FU, FT, FCD (1 M FT/0.4 M CDHP) and UFT (combination
      of FT and uracil). In rats bearing subcutaneous Yoshida sarcoma, S-1 inhibited
      tumor growth at the lowest dose (ED50 value: S-1 5, UFT 22, FT 82, FCD 5, and 5
      FU 19 mg/kg per day), and induced the least host body weight suppression, leading
      to the highest therapeutic index (TI) (S-1 4.5, UFT 1.4, FT 1.8, FCD 2.0, and 5
      FU 1.4). S-1 also showed a higher therapeutic effect than UFT against AH-130 and
      Sato lung carcinoma. After administration of S-1 and UFT at equitoxic doses, S-1
      showed a higher and more prolonged concentration of 5-FU than UFT both in plasma
      (AUC0-infinity: S-1 28 nmolh/ml, UFT 15 nmol.h/ml) and in tumor tissue (AUC0
      infinity: S-1 95 nmolh/g tissue, UFT 52 nmolh/g tissue), leading to a higher 5-FU
      level incorporated into the RNA fraction (F-RNA level) in tumor tissue (AUC0-24:
      S-1 7.0 nmolh/mg RNA, UFT 4.3 nmolh/mg RNA) and 5-8% higher thymidylate synthase
      (TS) inhibition in tumor tissue at every time-point through 24 h. Compared with
      other oral fluoropyrimidines after administration of the maximal tolerable dose
      (MTD), S-1 caused the lowest rates of intestinal toxicities, such as diarrhea and
      occult blood in feces. S-1 also showed a higher antitumor effect on Yoshida
      sarcoma implanted intracolonically than UFT at an equitoxic dose (tumor weight: S
      1 64 +/- 30 mg, UFT 133 +/- 52 mg; P < 0.05). These results suggest that CDHP,
      which is a potent inhibitor of 5-FU degradation, increases the antitumor activity
      of FT, and that Oxo, which is an inhibitor of 5-FU phosphorylation, locally
      protects the gastrointestinal tract from 5-FU-induced toxicity without decreasing
      the antitumor activity.

PMID- 8996523
TI  - The effects of terbium on the cellular accumulation of cisplatin in MDA-MB-231
      human breast tumor cells.
AB  - PURPOSE: Cisplatin (DDP) is an effective antitumor agent limited in its efficacy
      by the development of tumor cell resistance. The defective accumulation of DDP
      has been shown to be a prominent feature in many DDP-resistant cell lines. In an
      effort to circumvent this problem, we examined the cellular accumulation of DDP
      in the presence of terbium (Tb3+). We also examined the effects of verapamil on
      the cellular accumulation of DDP in order to delineate the specific interaction
      of Tb3+ and DDP. All experiments were performed on DDP-sensitive or DDP-resistant
      MDA-MB-231 human breast tumor cells. METHODS: The cellular accumulation of DDP
      and verapamil were determined by electrothermal atomic absorption
      spectrophotometry. Time-resolved luminescence spectroscopy was used to obtain
      equilibrium binding constants for the Tb3+/MDA cell complexes. RESULTS: We found
      that 100 microM Tb3+ increased DDP accumulation in the parent MDA cell line, 5.7
      fold resistant MDA/A13 and 10-fold resistant MDA/CH cells by 56.2 +/- 7.4, 71.9
      +/- 9.4 and 50.8 +/- 9.4%, respectively (P < 0.0001 for all MDA cell types). In
      contrast, 20 microM verapamil had no significant effect on DDP accumulation in
      the MDA cell lines. In addition, a positive correlation between the membrane
      binding of Tb3+ and the cellular accumulation of DDP was found to exist in the
      parent cell line and sublines (r = 0.9). CONCLUSIONS: In agreement with earlier
      studies, the plasma membrane of MDA cell lines contain a specific Tb(3+)-binding
      protein. Our findings suggest that the Tb(3+)-binding protein may be intimately
      associated with the accumulation of DDP in breast tumor cells.

PMID- 8996522
TI  - Toremifene concentration and multidrug resistance in lung tumors.
AB  - In this pharmacokinetics study, concentrations of toremifene (TOR), a new
      antiestrogen, were measured after a 7-day oral treatment in serum, lung, and
      tumor tissue to determine the optimal dose of TOR for the modulation of clinical
      multidrug resistance in patients with lung cancer. Target levels of the
      antiestrogen were based on previous in vitro studies. Altogether, 18 patients
      with operable lung tumors were studied. TOR was given in an open, nonrandomized,
      phase I study at three different dose levels. The medication consisted of oral
      TOR given for 7 days at either 240, 480, or 600 mg/day before surgical removal of
      the tumor. At least five patients were scheduled to be included at each dose
      level, with all five receiving the full course of therapy before escalation of
      the dose. Blood samples for serum TOR concentration measurements were taken on
      days 0 and 7. Specimens of tumor and normal lung tissue of approximately 0.5 g
      were taken on day 7. The concentrations of TOR and its metabolites were
      determined in serum, lung, and tumor tissue at different dose levels. Altogether,
      12 evaluable patients completed the scheduled treatment. The concentrations
      measured in serum, lung, and tumor tissue increased along with the dose used,
      such that the highest TOR values were achieved at 600 mg/day, with mean values
      being 4.9 mumol/l, 175.0 mumol/g, and 122.7 mumol/g, respectively. The
      concentrations of TOR and its metabolite N-demethyltoremifene were highest in
      lung tissue, but the values measured in tumor specimens were also well above the
      respective concentrations detected in serum samples. The TOR doses of 240 and 480
      mg/day were well tolerated. One patient in the group treated at 600 mg/day had to
      discontinue the treatment because of headache and nausea. TOR given at doses
      ranging from 480 to 600 mg/day for 7 days will produce serum, lung, and tumor
      concentrations of the parent drug and its metabolites that have been shown to
      reverse multidrug resistance of cancer cells in vitro. As the 480-mg/day dose of
      TOR produced tumor concentrations high enough to reverse multidrug resistance
      without producing adverse drug reactions, the dose recommended for the foreseen
      clinical trials in the reversal of multidrug resistance would be 480 mg/day for 7
      days.

PMID- 8996524
TI  - Cytotoxic peptides hemiasterlin, hemiasterlin A and hemiasterlin B induce mitotic
      arrest and abnormal spindle formation.
AB  - PURPOSE: Hemiasterlin, hemiasterlin A and hemiasterlin B are newly isolated
      cytotoxic tripeptides with potential as antitumor drugs. We wished to determine
      their mechanism of cytotoxicity. METHODS: We studied their effect on cell
      survival, cell cycle progression, and microtubule morphology in MCF-7 human
      mammary carcinoma cells. RESULTS: At the nanomolar concentrations at which they
      were cytotoxic, the peptides induced arrest in mitotic metaphase. Hemiasterlin A
      produced abnormal mitotic spindles like those produced by the microtubule
      inhibitors taxol, nocodazole and vinblastine at low concentrations. At high
      concentrations hemiasterlin A did not cause microtubule bundling like taxol, but
      caused microtubule depolymerization like nocodazole and vinblastine. CONCLUSIONS:
      The hemiasterlins probably exert their cytotoxic effect by inhibiting spindle
      microtubule dynamics.

PMID- 8996525
TI  - Phase I study of treatment with oral 13-cis-retinoic acid, subcutaneous
      interferon alfa-2a, cisplatin, and 24-hour infusion 5-fluorouracil/leucovorin.
AB  - A combination of oral 13-cis-retinoic acid (cis-RA) and subcutaneous interferon
      alfa-2a (IFN) has been reported to yield high response rates in patients with
      squamous cell carcinomas (SCCAs) of the cervix and skin. Cisplatin and 5
      fluorouracil with leucovorin (5-FU/LV) are chemotherapeutic agents commonly used
      for SCCAs. PURPOSE: To determine the maximum tolerated doses (MTDs) of cisplatin
      and 5-FU/LV when combined with IFN and cis-RA, and to define a recommended phase
      II regimen for testing in cervical cancer and other appropriate tumor types.
      METHODS: Phase I cohort design. Cisplatin was administered every 3 weeks. 5-FU
      and LV were administered together as a weekly 24-h infusion. Cis-RA was given
      orally twice daily. IFN was initially given subcutaneously at a dose of 3 million
      units (MU) daily. RESULTS: A total of 31 patients were treated. The IFN dose was
      reduced to 3 MU three times weekly because of patient intolerance. Cytopenias
      prevented the administration of weekly 5-FU/LV. Single-agent cisplatin with three
      times weekly IFN and twice daily cis-RA was tolerable. Four partial responses
      were observed, in patients with adrenal cancer, bladder cancer, gastric cancer,
      and adenocarcinoma of unknown primary. CONCLUSIONS: The recommended phase II
      regimen is cisplatin 100 mg/m2 every 3 weeks, IFN 3 MU three times weekly, and
      cis-RA 1 mg/kg daily. This appears to be more toxic than single-agent cisplatin,
      but the preliminary activity observed warrants further testing.

PMID- 8996526
TI  - Dihydropyrimidine dehydrogenase inactivation and 5-fluorouracil pharmacokinetics:
      allometric scaling of animal data, pharmacokinetics and toxicodynamics of 5
      fluorouracil in humans.
AB  - The pharmacokinetics of 5-fluorouracil (5-FU) in different animal species treated
      with the dihydropyrimidine dehydrogenase (DPD) inactivator, 5-ethynyluracil
      (776C85) were related through allometric scaling. Estimates of 5-FU dose in
      combination with 776C85 were determined from pharmacokinetic and toxicodynamic
      analysis. METHOD: The pharmacokinetics of 5-FU in the DPD-deficient state were
      obtained from mice, rats and dogs treated with 776C85 followed by 5-FU. The
      pharmacokinetics of 5-FU in humans were then estimated using interspecies
      allometric scaling. Data related to the clinical toxicity for 5-FU were obtained
      from the literature. The predicted pharmacokinetics of 5-FU and the clinical
      toxicity data were then used to estimate the appropriate dose of 5-FU in
      combination with 776C85 in clinical trials. RESULTS: The allometric equation
      relating total body clearance (CL) of 5-FU to the body weight (B) (CL =
      0.47B0.74) indicates that clearance increased disproportionately with body
      weight. In contrast, the apparent volume of distribution (Vc) increased
      proportionately with body weight (Vc = 0.58 B0.99). Based on allometric analysis,
      the estimated clearance of 5-FU (10.9 l/h) in humans with DPD deficiency was
      comparable to the observed values in humans lacking DPD activity due to genetic
      predisposition (10.1 l/h), or treatment with 776C85 (7.0 l/h) or (E)-5-(2
      bromovinyl)-2'-deoxyuridine (BVdUrd, 6.6 l/h). The maximum tolerated dose (MTD)
      of 5-FU in combination with 776C85 was predicted from literature data relating
      toxicity and plasma 5-FU area under the concentration-time curve (AUC). Based on
      allometric analysis, the estimated values for the MTD in humans treated with
      776C85 and receiving 5-FU as a single i.v. bolus dose, and 5-day and 12-day
      continuous infusions were about 110, 50 and 30 mg/m2 of 5-FU, respectively.
      DISCUSSION: The pharmacokinetics of 5-FU in the DPD-deficient state in humans can
      be predicted from animal data. A much smaller dose of 5-FU is needed in patients
      treated with 776C85.

PMID- 8996527
TI  - Amelioration of methotrexate-induced malabsorption by vitamin A.
AB  - Methotrexate (MTX) induces damage to the small intestine, resulting in
      malabsorption and diarrhea. We found that the coadministration of vitamin A (VA)
      with MTX protected the small intestine from MTX-induced damage. In this study,
      the permeability of D-glucose, D-xylose and L-leucine through the small intestine
      of rats treated with MTX and/or VA was studied using everted segments of small
      intestine. MTX treatment decreased permeability and VA coadministration prevented
      the decrease. The transport of D-glucose in the small intestine of MTX plus VA-
      and VA-treated rats and of control rats followed Michaelis-Menten kinetics, in
      contrast to the transport kinetics in MTX-treated rats. The pharmacokinetics of
      orally administered [14C]-D-glucose in control rats and MTX- and/or VA-treated
      rats was also studied. The bioavailability of D-glucose in MTX-treated rats was
      lower than in the other three groups. VA coadministration improved the
      bioavailability of D-glucose. Thus, it seems likely that VA ameliorates MTX
      induced malabsorption.

PMID- 8996528
TI  - DNA damage inducible-gene expression following platinum treatment in human
      ovarian carcinoma cell lines.
AB  - PURPOSE: DNA damage-inducible genes, such as gadd153, gadd45, p21 and c-jun, have
      previously been shown to be induced by the chemotherapeutic agent cisplatin. One
      of these genes, gadd153, has previously been reported to be differentially
      expressed in cisplatin-resistant cell lines and, therefore, to be a potential
      prognostic indicator for tumor response to cisplatin-based chemotherapy. It is
      not currently known whether such damage-inducible genes are turned on by the DNA
      damage itself (e.g. by the formation of Pt-DNA adducts) or by the downstream
      biological consequences of that damage. It is also not known whether the
      increased expression of these DNA-damage-inducible genes is related to immediate
      protective responses such as DNA repair or to more delayed responses such as cell
      cycle arrest or apoptosis. These experiments were initiated to characterize more
      fully the nature of the DNA damage-inducible response to cisplatin treatment and
      to determine whether any of these genes might be useful prognostic indicators of
      tumor response to cisplatin chemotherapy. METHODS: The dose-response and time
      course for the induction of the DNA damage-inducible genes gadd153, gadd45, p21
      and c-jun were examined by Northern analysis in the human ovarian carcinoma cell
      line 2008 and its resistant subclone C13* following treatment with platinum
      anticancer agents. The extent of gene expression was correlated with cytotoxicity
      determined by growth inhibition assay, Pt-DNA adducts determined by atomic
      absorption spectrometry and inhibition of DNA synthesis determined by 3H
      thymidine incorporation. RESULTS: All four genes were induced maximally in both
      sensitive and resistant cell lines at lethal cisplatin doses (> or = ID90).
      Induction was maximal between 24 and 48 h following exposure to the drug for all
      genes except c-jun which was induced by 6 h. At 24 h following cisplatin
      treatment the overall levels of gadd153 were less in the resistant C13* cell line
      than in the parental 2008 cell line, while those of gadd45 were greater in C13*
      than in 2008. Maximal expression of p21 and c-jun was not significantly different
      in the two cell lines. The dose-response of these genes correlated with the
      cytotoxicity of cisplatin and the inhibition of DNA synthesis by cisplatin,
      rather than to the actual levels of Pt-DNA adducts. The more cytotoxic platinum
      analog, ormaplatin, also induced gadd153 and its induction was also based on
      cytotoxicity. CONCLUSION: These results suggest that the regulation of gadd153
      and gadd45 expression occurs thorough separate pathways in the 2008 and C13* cell
      lines. The DNA damage-inducible gene response for all four damage-inducible genes
      tested appeared to be more directly correlated with downstream biologic effects
      of cisplatin damage than with actual Pt-DNA adduct levels. The time-course and
      dose-response for induction of these genes was more consistent with delayed
      responses such as apoptosis rather than more immediate responses such as DNA
      repair. Finally, these results strengthen previous suggestions that the
      expression of gadd153, and possibly other DNA damage-inducible genes, may be
      useful indicators of tumor response to cisplatin-based chemotherapy.

PMID- 8996529
TI  - Pharmacokinetics and toxicity of 120-hour continuous-infusion hydroxyurea in
      patients with advanced solid tumors.
AB  - A group of 18 patients with advanced cancer were entered on a phase I study of a
      120-h continuous intravenous infusion of hydroxyurea. The dose of hydroxyurea was
      escalated in cohorts of patients from 1 to 2 to 3.2 g/ m2 per day. The primary
      dose-limiting toxicity was neutropenia, often accompanied by leukopenia,
      thrombocytopenia and generalized skin rash. Prophylactic treatment of patients
      with dexamethasone and diphenhydramine hydrochloride prevented the skin rash, but
      not the hematopoietic toxicities. The pharmacokinetics of hydroxyurea were
      studied in all patients. The steady-state concentrations of hydroxyurea were
      linearly correlated with the dose (R2 = 0.71, n = 18, P < 0.0001). The mean +/-
      SE concentrations were 93 +/- 16, 230 +/- 6 and 302 +/- 27 microM at 1, 2 and 3.2
      g/m2 per day, respectively. The mean +/- SE renal and nonrenal clearances of
      hydroxyurea were 2.14 +/- 0.18 and 3.39 +/- 0.28 l/h per m2 (n = 16), neither of
      which correlated with the dose. The concentration of hydroxyurea in plasma
      decayed monoexponentially with a mean +/- SE half-life of 3.25 +/- 0.18 h (n =
      17). The steady-state concentration of hydroxyurea was > 200 microM in all nine
      patients treated at 2 g/m2 per day, a dose which was well tolerated for 5 days.
      We recommend this dose for phase II trials in combination with other
      antineoplastic agents.

PMID- 8996530
TI  - Comparison of the potency of glycosylated and nonglycosylated recombinant human
      granulocyte colony-stimulating factors in neutropenic and nonneutropenic CD rats.
AB  - Recent studies in human bone-marrow culture and healthy human volunteers suggest
      that lenograstim [glycosylated, recombinant human granulocyte colony-stimulating
      factor (rHuG-CSF) produced in Chinese hamster ovary (CHO) cells] has greater in
      vivo potency than filgrastim [nonglycosylated, methionine-extended recombinant
      human granulocyte colony-stimulating factor (rmetHuG-CSF) produced in Escherichia
      coli]. To confirm and extend these results we investigated the in vivo potency of
      both products in normal rats and neutropenic CD rats as an animal model of
      chemotherapy-induced neutropenia. In normal rats, groups of eight normal male CD
      rats received four subcutaneous doses of 10, 30, or 100 micrograms/kg filgrastim
      or lenograstim on days 1-4 of the study, whereas a control group received the
      vehicle. Blood samples were collected from each animal before treatment (day -5)
      and on days 2, 3, 5, 8, and 12 of the study for determination of red blood cell
      (RBC), platelet, white blood cell (WBC), and differential counts. rHuG-CSF and r
      metHuG-CSF produced increased WBC counts, principally due to elevated absolute
      neutrophil counts (ANCs); on days 2, 3, and 5, all groups receiving rG-CSF had
      ANCs that increased in a progressive and dose-related manner. With the exception
      of a single value, mean ANCs obtained on days 2, 3, and 5 in lenograstim-treated
      groups were higher (statistically significant on day 3 at 30 and 100
      micrograms/kg and on day 5 at 10, 30, and 100 micrograms/kg) than the respective
      values obtained in filgrastim-treated groups. No compound-related effect was
      noted in RBC or platelet parameters. Neutropenia was induced in male CD rats (12
      animals/group) with a single intraperitoneal dose of 50 mg/kg cyclophosphamide
      (CPA) on day 0. On days 1-4, CPA-treated groups were treated with the vehicle
      (control) or with filgrastim or lenograstim at 30 or 100 micrograms/kg per day.
      An additional group was not treated with CPA and served as the absolute control
      group. Blood was collected from alternating subgroups on study day -5 (pretest)
      and on days 2, 3, 4, 5, 6, 8, 9, and 12 for determination of RBC, platelet, WBC,
      and differential counts. No major adverse in-life effect was noted in neutropenic
      rats. Maximal depression of WBCs and ANCs occurred on day 5, followed by recovery
      to normal values by days 9 (ANC) and 12 (WBC). On day 3 and days 5-9, rHuG-CSF-
      and metHuG-CSF-treated groups had marked and dose-related increases in WBCs as
      compared with CPA-treated controls, principally due to elevated ANCs. With the
      exception of a few values, mean ANC values obtained in lenograstim-treated groups
      were consistently higher than the respective values obtained in filgrastim
      treated groups; the difference was statistically significant on day 3 (30
      microgram/kg groups) and on days 6 and 8 (100-microgram/kg groups). In
      conclusion, treatment of normal and neutropenic CD rats with lenograstim resulted
      in a dose-related elevation of ANCs that was consistently and significantly
      higher than the response to identical doses of filgrastim. These results suggest
      that lenograstim, the glycosylated form of rG-CSF, has superior in vivo potency
      in normal and neutropenic animals as compared with filgrastim, the
      nonglycosylated form of rG-CSF.

PMID- 8996531
TI  - Continuous intratumoral microdialysis during high-dose methotrexate therapy in a
      patient with malignant fibrous histiocytoma of the femur: a case report.
AB  - We used a microdialysis technique to assay intratumoral methotrexate (MTX) levels
      during high-dose (12 g/m2 given as a 4-h infusion) therapy in a 43-year-old man
      with a malignant fibrous histiocytoma in the medial femoral condyle. Additional
      microdialysis probes were implanted in muscle tissue contralateral to the tumor
      and in an antecubital vein. Microdialysis was attempted during the initial two
      high-dose courses, but the two latter probes were removed at the start of the
      second treatment cycle due to leakage. No attempt to correct for microdialysis
      recovery was made. The intratumorally localized probe gave reproducible data on
      tumor MTX exposure of 9.3-14% of unbound systemic MTX. There was a close
      correlation between tumor and systemic levels for both MTX and its major
      extracellular metabolite 7-hydroxymethotrexate. Although limited to the study of
      MTX pharmacokinetics in a single subject, the experiment demonstrates that
      intratumoral microdialysis may provide data on tumor drug exposure, although of
      an indirect nature and dependent on the probe characteristics, the flow rate,
      and, possibly, the time after probe implantation. We propose that the application
      of microdialysis may prove useful for elucidation of the relationship between
      local drug exposure and the therapeutic response in normally inaccessible
      compartments during cancer pharmacotherapy.

PMID- 8996532
TI  - Opiate effects on 5-fluorouracil disposition in mice.
AB  - PURPOSE: This study was performed to investigate the effects of morphine on the
      disposition of 5-fluorouracil (5-FU). METHODS: Mice were injected subcutaneously
      (s.c.) with saline or morphine, 20 mg/kg. 5-FU was administered intravenously
      (i.v.) 30 min later as a single bolus or by constant infusion. Blood samples were
      obtained by orbital sinus puncture. Urine samples were obtained from the bladder
      after ligation of the external urethra. 5-FU concentrations in plasma and urine
      were determined by HPLC. RESULTS: Morphine markedly elevated plasma levels of 5
      FU given at doses of 100 to 860 mg/kg. The plasma clearance rate of a bolus dose
      of 100 mg/kg 5-FU was significantly reduced from 54 to 28 ml/min per kg and the
      elimination half-life was increased from 6.9 to 12.2 min by prior administration
      of morphine. When 5-FU was infused at 0.5 mg/kg per min, morphine reduced its
      plasma clearance rate from 145 to 94 ml/min per kg. Mice made tolerant by prior
      morphine administration required higher doses of this opiate to raise 5-FU levels
      as well as to cause analgesia. The effects of morphine on 5-FU disposition were
      antagonized by naltrexone. Excretion of 5-FU in urine was not affected by
      morphine treatment. CONCLUSIONS: The plasma clearance rate of 5-FU in mice is
      significantly reduced by concomitant use of morphine. This effect of morphine is
      due to reduced hepatic elimination of 5-FU rather than to a decrease in its renal
      excretion.

PMID- 8996533
TI  - Predictive value of argyrophilic nucleolar-organizer-region-associated proteins
      in bladder cancer, using cell-imprint preparations.
AB  - The predictive value of quantifying argyrophilic nucleolar-organizer-region
      associated proteins (Ag-NOR) in routinely processed paraffin-embedded tissue
      sections of bladder cancer remains controversial. The purpose of this study was
      to determine whether cell-imprint preparations facilitate a more accurate
      determination of the mean number of Ag-NOR per cell (Ag-NOR score). The utility
      of using the Ag-NOR scores of cell-imprint preparations as a prognostic indicator
      in patients with bladder cancer was explored. We evaluated 90 patients with newly
      diagnosed bladder cancer using cell-imprint preparations to determine Ag-NOR
      score. The score significantly correlated with known prognostic factors
      associated with this tumor, including histological grade (P < 0.001),
      pathological stage (P < 0.01), and papillary structure (P < 0.001). Furthermore,
      the Ag-NOR score appeared to be an independent predictor of intravesical tumor
      recurrence of superficial bladder cancer (P < 0.05). These results suggest that
      the Ag-NOR score determined in a cell imprint preparation may serve as a useful
      prognostic indicator in bladder cancer.

PMID- 8996534
TI  - Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of
      lobaplatin and oxaliplatin in cultured SW 1573 cells.
AB  - The cytotoxicity of cisplatin and cisplatin-DNA adduct formation in vitro and in
      vivo is clearly enhanced by hyperthermia. We investigated whether cytotoxicity
      and platinum-DNA adduct formation of two promising new third-generation platinum
      derivatives, lobaplatin [1,2-diamminomethylcyclobutane platinum(II) lactate] and
      oxaliplatin [oxalato-1,2-diaminocyclohexane platinum(II)], are also enhanced by
      hyperthermia. Cisplatin was used for comparison. SW 1573 cells were incubated
      with cisplatin, lobaplatin or oxaliplatin at different concentrations for 1 h at
      37 degrees, 41 degrees and 43 degrees C. The reproductive capacity of cells was
      determined by cloning experiments. Immunocytochemical detection of platinum-DNA
      adducts was performed with the rabbit antiserum NKI-A59. At 37 degrees C,
      cisplatin was the most cytotoxic, followed by oxaliplatin and lobaplatin.
      Hyperthermia clearly enhanced the cytotoxicity of cisplatin, lobaplatin and
      oxaliplatin. There was no further increase in cytotoxicity at 43 degrees C
      compared to 41 degrees C for cisplatin and oxaliplatin. A further increase in
      cytotoxicity at 43 degrees C was observed for lobaplatin. At 43 degrees C thermal
      enhancement was higher for lobaplatin than for oxaliplatin, with the reverse
      pattern at 41 degrees C. For both drugs, thermal enhancement of cytotoxicity was
      lower than observed for cisplatin. Immunocytochemical detection of platinum-DNA
      adducts was feasible for all the drugs. Adduct formation was enhanced at 43
      degrees C for cisplatin, lobaplatin and oxaliplatin with a relative increase of
      410%, 170% and 180%. These results seem to confirm that an increase in platinum
      DNA adduct formation is involved in the in vitro thermal enhancement of
      cytotoxicity. The observed thermal enhancement of cytotoxicity of lobaplatin and
      oxaliplatin in vitro warrants further in vivo investigations.

PMID- 8996535
TI  - Regulation of matrilysin expression in cells of squamous cell carcinoma by E
      cadherin-mediated cell-cell contact.
AB  - A critical attribute of invasive carcinomas is their ability to degrade
      components of the extracellular matrix, a process achieved by the matrix
      metalloproteases. In the human squamous cell carcinoma cell line II-4, mRNA and
      protein expression of the matrix metalloprotease matrilysin was observed to be
      significantly higher in confluent than in log-phase growth conditions. The
      purpose of this study was to determine the basis for this switch in constitutive
      matrilysin expression. Conditioned medium from confluent cultures did not induce
      matrilysin in log-phase cultures, nor did conditioned medium from log-phase
      cultures repress matrilysin expression in confluent cultures. Thus, matrilysin
      expression was found not to be controlled by factors autocrine product.
      Matrilysin protein levels were, however, found to be directly correlated to the
      degree of cell-cell contact. Incubation of confluent cultures in 30 microM
      calcium medium, which disrupts E-cadherin-mediated cell-cell contact, was
      subsequently found to inhibit matrilysin expression, as did treatment with an
      anti-E-cadherin-neutralizing antibody. These results demonstrate that the degree
      of cell-cell contact mediated by the E-cadherin cell-adhesion molecule can
      influence constitutive metalloprotease expression levels in cultured squamous
      cell carcinoma cells.

PMID- 8996536
TI  - Cyclosporin A enhances locoregional metastasis of the CC531 rat colon tumour.
AB  - The immunosuppressive drug cyclosporin A has been evaluated recently in phase II
      trials in cancer therapy as a reverter of P-glycoprotein-mediated multidrug
      resistance. As an immunosuppressive agent, cyclosporin A potentially can enhance
      tumour growth. We investigated this potency of cyclosporin A in the weakly
      immunogenic CC531 colon adenocarcinoma model, using the same dose that had
      previously been shown to intensify the antitumour activity of doxorubicin in
      vivo. In vitro cyclosporin A caused no growth acceleration and only in high doses
      was growth inhibition of CC531 cells observed. In vivo no evidence of growth
      enhancement was found in short-term assays but, after 4 weeks, rats treated with
      cyclosporin A had a significantly higher tumour load, mainly consisting of
      locoregional metastases. These experiments in the CC531 tumour model show that
      cyclosporin A, used as a reverter of multidrug resistance, may produce short-term
      improvement of antitumour activity but may also induce enhancement of tumour
      metastasis.

PMID- 8996538
TI  - Amputation and dexniguldipine as treatment for canine appendicular osteosarcoma.
AB  - The biological behavior of osteosarcoma in dogs is similar to that in humans and
      the dog has been suggested as a model for the disease in humans. Because occult
      metastatic disease is common at presentation, systemic therapy is necessary. The
      dihydropyridine, dexniguldipine hydrochloride (B859-35), is a potent inhibitor of
      protein-kinase-C(PKC)-stimulated cell proliferation and has shown therapeutic
      activity in experimentally induced neuroendocrine hamster lung tumors and in a
      mammary cancer cell line. In human osteosarcoma cell lines, PKC activity can be
      down-regulated, resulting in increased sensitivity to cisplatin. Since these
      results supported the involvement of PKC inhibitors in the therapeutic management
      of osteosarcoma, we performed a prospective, randomized clinical trial using dogs
      with naturally occurring appendicular osteosarcoma to determine the therapeutic
      potential of dexniguldipine. Dogs received either no drug treatment (control
      group, n = 8), standard treatment (e.g., cisplatin, n = 14), or dexniguldipine
      treatment (n = 14) following amputation. Dexniguldipine- and cisplatin-treated
      dogs had a longer median remission duration and survival time than untreated dogs
      (P < 0.05); however, dexniguldipine-treated dogs had a shorter survival time than
      cisplatin-treated dogs (P < 0.05). The results of this study demonstrate that
      dexniguldipine has significant activity in the inhibition of canine osteosarcoma
      micrometastases. The identification of a tumor model that may be responsive to
      this class of antiproliferative agents warrants further clinical investigation to
      determine the optimum dosage of dexniguldipine and the role it may have in the
      therapeutic management of canine osteosarcoma.

PMID- 8996537
TI  - Apoptosis of human BEL-7402 hepatocellular carcinoma cells released by antisense
      H-ras DNA--in vitro and in vivo studies.
AB  - Recent findings suggest that over-expression of activated H-ras inhibited
      apoptotic cell death by blocking the activity of apoptotic endonuclease(s). This
      study was designed using antisense H-ras oligodeoxynucleotides (ODN) to evaluate
      whether alterations of H-ras expression in BEL-7402 human hepatocellular
      carcinoma cells could influence the induction of apoptosis in vitro and in vivo.
      We found that, in vitro, continuous suppression of H-ras expression could
      decrease the proliferation of BEL-7402 cells and inhibit H-ras-induced entry into
      S phase. In situ end labeling showed that a large number of cells underwent
      apoptotic cell death after treatment with antisense H-ras ODN (P < 0.01), and gel
      electrophoresis of DNA extracted from these cells demonstrated a typical DNA
      ladder, characteristic of apoptosis. In vivo study indicated that pretreatment
      with antisense H-ras significantly retarded tumor growth in comparison with the
      untreated controls or tumors treated with non-specific ODN (P < 0.01, P < 0.01).
      In situ end-labeling revealed that pronounced apoptotic nuclei were also present
      in the tissue treated with antisense H-ras ODN (P < 0.01). Immunocyto
      histochemical study showed that expression of p21H-ras was significantly
      decreased after treatment with antisense H-ras. These results indicate that
      suppression of H-ras over-expression by antisense ODN could effectively inhibit
      tumor growth and revive the apoptotic pathway by releasing the activity of
      apoptotic endonuclease(s). The data also suggest the need for further studies to
      elucidate molecular events involved in antisense H-ras-released apoptosis and
      evaluate its therapeutic implications.

PMID- 8996539
TI  - DNA ploidy and protein synthesis in squamous cell carcinoma cell lines of the
      head and neck.
AB  - Aneuploidy as abnormal nuclear DNA content, is considered almost positive
      evidence of malignancy. In this study three diploid and three aneuploid squamous
      cell carcinoma (SCC) cell lines were examined for DNA content by flow cytometry.
      The DNA indices of the SCC cell lines were found to range from 1.0 to 2.1. The
      mitotic activity of the diploid cell lines was 1.6 times higher and the cells
      were smaller than aneuploid cells. To find a molecular basis for these
      differences, the pattern of the de-novo synthesized proteins was analyzed by
      means of [35S]methionine incorporation, electrophoresis, and autoradiography. In
      all aneuploid SCC cell lines tested in this experiment, the increase of nuclear
      DNA content is associated with the synthesis of a novel protein with a molecular
      mass of approximate 55 kDa as well as with altered synthesis rates of two
      preexisting proteins (50 kDa and 100 kDa). For determination of the amino acid
      uptake in diploid and aneuploid cells, the accumulation of [35S]methionine was
      measured as a function of time by liquid scintillation counting. No significant
      difference was found in the uptake rate between diploid and aneuploid cells with
      the same protein content. However, discrepancies were revealed when equal numbers
      of cells with different DNA index were used, suggesting, that protein turnover is
      different in diploid and aneuploid SCC cells.

PMID- 8996541
TI  - The impact of intraoperative brachytherapy on surgery of Ewing's sarcoma.
AB  - Surgery of Ewing's sarcoma sometimes results in an inadequate surgical margin.
      The influence of intraoperative brachytherapy on local control of the tumor,
      operation time, blood loss, and surgical complications was evaluated, comparing
      the results of 20 patients who received brachytherapy to a series of 42 patients
      receiving surgery without brachytherapy. The dose of intraoperative brachytherapy
      ranged between 9 Gy and 21 Gy. The average operation time was longer in 20 cases
      with brachytherapy (7.9 h) than in 42 cases without brachytherapy (4.3 h) (P <
      0.0001). The average blood loss in the groups with (3531 ml) and without
      brachytherapy (3515 ml) was comparable (P = 0.3840). The surgical complication
      rate in patients receiving brachytherapy was also similar to that of untreated
      patients (30% versus 31%, P = 0.7690). Local relapse developed in 1 of 20
      patients who received brachytherapy and 1 of 42 patients without brachytherapy.
      On the basis of this analysis, it can be concluded that this procedure is safe
      and does not increase of the acute complication rate. The latest results of local
      controls are awaited.

PMID- 8996540
TI  - Octreotide combined with goserelin in the therapy of advanced pancreatic cancer-
      results of a pilot study and review of the literature.
AB  - The two hormone analogues octreotide and goserelin have been shown to decelerate
      growth of human pancreatic cancer in vitro and in vivo. The objective of this
      pilot study was to investigate the efficacy and toxicity of the combination of
      these two agents in patients with advanced pancreatic cancer. Octreotide was
      injected subcutaneously in dosages increasing weekly, starting with 50 micrograms
      twice daily, until the level of maintenance therapy of 500 micrograms three times
      a day was reached. In addition, 3.8 mg goserelin acetate was administered
      subcutaneously at monthly intervals. A median of 7 cycles (range 1-27 cycles)
      were applied; 13 out of 14 patients entered into the study were evaluable for
      response and all 14 were evaluated for toxicity. In one patient with initially
      non-resectable pancreatic cancer, systemic therapy yielded a partial remission
      lasting 9 months. The degree of tumour regression then allowed a consecutive
      macroscopic radical tumour resection followed by an additional 6 months of no
      evidence of disease while the same drug combination was continued. In an
      additional 9 patients, no change of disease was observed, in some cases for a
      remarkably long time (up to 27 months). Nevertheless, the objective response rate
      of 7% (95% confidence interval 0 +/- 21%) was low. In 5 patients a clear
      improvement in their performance status was seen soon after the start of therapy;
      3 patients showed progression of the disease at first evaluation or earlier and 1
      patient was not evaluable at the time of study assessment. According to the
      product-limit method of Kaplan and Meier, the time to progression was 3.0 +/- 1.8
      months [median +/- asymptotic standard error (ASE)] and overall survival was 6.0
      +/- 1.5 months (median +/- ASE). Toxicity was rare and only of mild to moderate
      degree. Overall, the regimen under investigation did not meet the criteria for
      sufficient antitumoural effectiveness. Nevertheless, this study reinforces the
      concept that pancreatic cancer is principally responsive to endocrine therapy and
      therefore the further investigation of hormonal manipulation seems worth while in
      the future.

PMID- 8996542
TI  - Surgical complications after preoperative irradiation of Ewing's sarcoma.
AB  - The influence of preoperative irradiation on surgical complications in 42
      patients with Ewing's sarcoma was analysed. After preoperative irradiation and
      chemotherapy, 35 of 40 patients showed a good histological response and 25 of 40
      patients had no viable tumour cells in the resected specimen. Local relapse alone
      did not develop, local relapse and metastasis developed in 2 patients and
      metastasis alone in 15 patients. Surgical complications appeared in 12 of 42
      patients: 9 of 19 central tumours (19 pelvic lesions), 1 of 13 proximal and 2 of
      10 distal tumours. Surgical complications after preoperative irradiation are
      distributed as follows: delayed wound healing 8, hematoma 2, thrombosis 2, skin
      infection 1, and abscess 1. On the other hand, complications appeared in 2 of 28
      patients without preoperative irradiation: none in 9 patients having central
      tumours including 2 pelvic lesions, 1 in 12 patients with proximal tumours, and 1
      in 7 patients with distal tumours. The multivariate regression test showed that
      the tumour site (central) is an influencing factor in the appearance of surgical
      complications. In central tumours, the surgical complication rate increases after
      preoperative irradiation; however, it is affected by the increase of the ratio of
      patients with pelvic tumours.

PMID- 8996543
TI  - Prognostic value of epidermal growth factor expression in breast cancer.
AB  - A series of 198 female breast cancer biopsies were analysed immunohistochemically
      for the expression of epidermal growth factor (EGF), with special emphasis on its
      prognostic significance. A total of 67/198 tumours (33.8%) were EGF-positive, 24
      (12%) of which showed strong expression of EGF. EGF was usually expressed in the
      cytoplasm of the cancer cells but, in 22 cases, the normal ducts adjacent to the
      cancer showed positive staining as well. Strong EGF expression was related to
      distant metastases at diagnosis (P = 0.04). Oestrogen(ER)- and progesterone
      receptor(PR)-negative tumours showed EGF positivity with equal frequency (P =
      0.05 in both). Axillary lymph node status, histological type, tumour size,
      histological grade, S-phase fraction, mitotic index or cancer recurrence did not
      show any statistical correlation with EGF expression. Tumour size (P = 0.007),
      axillary lymph node involvement (P = 0.003) and ER content (P = 0.03) were
      independent prognostic factors in multivariate survival analysis, whereas EGF
      positivity, as an independent factor, had no effect on survival. In univariate
      analysis, however, EGF positivity predicted a more favourable outcome in axillary
      lymph-node-positive tumours (P = 0.04). The results suggest that
      immunohistochemical assessment of EGF expression has hardly any clinical
      significance in addition to the well-established prognostic factors in breast
      cancer.

PMID- 8996544
TI  - BRCA1 mutations and phenotype.
AB  - More than 100 mutations have been described for the breast-cancer-susceptibility
      gene BRCA1. The paper describes phenotypical aspects of three selected mutations
      located at the beginning, in the middle, and at the end of the gene. A remarkable
      decrease of the age of diagnosis of the mammary carcinoma is observed with
      increasing length of the putative gene product, combined with greater severity of
      the disease.

PMID- 8996545
TI  - A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal
      antibody in oncogenesis.
AB  - Glycoconjugates and their antibodies are vital components of host-tumor
      interaction. This review concentrates on the oncological implications of research
      concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal),
      the enzyme responsible for its construction, alpha 1,3 galactosyl transferase
      (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes,
      previously assumed to be absent from human tissue, have been demonstrated on
      several human cancer cell lines, senescent red blood cells, and Graves' disease
      thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased
      metastatic formation in animal models. The mechanisms of human response to these
      neoantigens are complex, as natural anti-gal antibodies exist in high titers in
      normal sera, thus predicting immunological recognition of cells expressing alpha
      gal epitopes. Hypotheses vary regarding the pathogenic contributions of
      metastasis-associated phenomena such as de novo expression of alpha gal and its
      unmasking by desialylation. The means by which alpha gal is sporadically
      expressed in human tissue remain unknown, as the galactosyl transferase which
      produces this epitope in constitutively expressive animals has undergone
      significant mutation at the genomic level in humans. Pathological re-expression
      is presumed to require permissive changes at a cellular level. Detailing these
      alterations is a prerequisite to the comprehension of the metastatic phenotype.
      In this context, the possibility of therapeutic strategies affecting alpha gal
      expression are also discussed.

PMID- 8996546
TI  - Stimulation of 1-(beta-D-arabinofuranosyl)cytosine (AraC)-induced apoptosis in
      the multidrug resistant human promyelocytic leukemia cell lines with protein
      kinase inhibitors.
AB  - Stimulation of apoptosis induced by 1-(beta-D-arabinofuranosyl)cytosine (AraC)
      with protein kinase inhibitors (i.e. staurosporine, CGP 41251-a protein kinase C
      (PKC)-selective staurosporine derivative and protein tyrosine kinase (PKT)
      inhibitor genistein) was examined in two human multidrug-resistant promyelocytic
      leukemia (HL-60) cell lines with different cell membrane drug resistance
      associated glycoproteins (i.e. HL-60/VCR:MDR1 gene coded Pgp/p170 and HL-60/ADR:
      MRP gene coded non-Pgp/p190). Staurosporine stimulated AraC-induced apoptosis in
      the parental drug-sensitive HL-60 cells and both examined multidrug resistant HL
      60 sublines. The stimulation of AraC-induced apoptosis by PKC selective inhibitor
      CGP 412251 and PTK-inhibitor genistein was approximately equal to that of
      staurosporine in HL-60/ADR cell line. In both parental drug sensitive HL-60 cells
      and Pgp/p170 positive (MDR1) HL-60/VCR, staurosporine-stimulated AraC-induced
      apoptosis was higher than that stimulated by the PKC selective CGP 41251
      inhibitor, or PTK-inhibitor genistein. These data suggest that the molecular
      pathway(s) for AraC-induced apoptosis can be activated and stimulated by PKC- and
      PTK-inhibitors in both examined drug-resistant HL-60 cell lines. Furthermore,
      these data suggest that although both PKC- and PTK-dependent mechanisms are
      involved in AraC-induced apoptosis, in the drug-sensitive HL-60 cells and
      multidrug-resistant HL-60/VCR (Pgp/p170) cells this process is mediated at least
      partially, also by PKC- and PTK-independent mechanisms, activated by
      staurosporine.

PMID- 8996547
TI  - Leukocyte alkaline phosphatase and serum alkaline phosphatase in patients with
      metastatic breast and colon cancer.
AB  - Peripheral blood leukocyte alkaline phosphatase (LAP) scores and serum alkaline
      phosphatase (SAP) levels in 70 patients with metastatic breast and colorectal
      cancer (metastases to the liver, lung, bone and abdomen) and in 18 healthy
      controls were measured. The mean LAP score in the metastatic cancer patients was
      significantly higher than in the control group (244 vs. 61) and there was no
      overlap between the 95% confidence level intervals of the two groups. The mean
      (SAP) level in the metastatic patients was also higher than in the controls (249
      u/l vs. 162 u/l) but the 95% confidence level interval of the controls was inside
      the 95% interval of the metastatic patients meaning that considerable percentage
      of the metastatic patients will have a SAP level within the normal range. We
      conclude that of the two markers, the LAP is the better one for detection of
      metastatic tumors.

PMID- 8996548
TI  - Comparison of fluorescent in situ hybridization (FISH) and the polymerase chain
      reaction (PCR) for detection of residual neuroblastoma cells.
AB  - Residual neuroblastoma (NB) cells in bone marrow or peripheral progenitor
      hematopoietic cells harvests may be a source of relapse after autologous
      transplantation in patients with high stage neuroblastoma. Therefore a sensitive
      method for detecting minimal residual disease (MRD) in the harvested product is
      important so that an appropriate purging techniques can be applied and optimized.
      We report on the detection of NB cells by fluorescence in situ hybridization
      (FISH) for N-myc amplification and compare the sensitivity of FISH with a
      semiquantitative polymerase chain reaction (PCR) assay. As a model of MRD we used
      the neuroblastoma cell line IMR-32 diluted with normal peripheral blood
      lymphocytes. We were able to detect a single NB cell in 1000 normal mononuclear
      cells by FISH. The PCR method, using ethidium-bromide-stained gels, required at
      least 10% NB cells to be present for detection of an amplified band of the N-myc
      oncogene. Thus, FISH is ten to one hundred times more sensitive in detection of N
      myc amplification than a differential PCR and thus it is the method of choice for
      detection of MRD in NB patients.

PMID- 8996549
TI  - p53 gene mutation in relation to p53 protein accumulation in male and female
      breast cancer.
AB  - The aim of this investigation was to study the prevalence of p53 gene mutations
      in male and female breast cancers and to find out the relationship between this
      event and p53 protein expression. Genomic p53 was amplified by polymerase chain
      reaction (PCR). Exons 5-8 were screened for mutations using single stranded
      conformation polymorphism (SSCP) analysis. P53 protein expression was detected by
      immunohistochemistry (IHC) with the monoclonal antibody DO-1. In female breast
      cancer, p53 gene mutation was detected in 33% cases in either exon 5 or 6.
      However, in male, mutation was detected only in exon 6 in 90% cases. On the other
      hand, p53 protein expression was observed in all of these cases. Moreover, p53
      protein immunostaining was observed in some of those cancer tissues, where no
      mutation was detected in exons 5-8. P53 dysfunction, as indicated by mutation or
      increased protein expression, common in both male and female breast cancer, but
      rate of occurrence or site of mutation differ from each other. Our results in
      male breast tumors indicate a positive correlation between p53 mutation and p53
      protein overexpression, whereas the results in female breast tumors indicate an
      overexpression of p53 protein even without p53 gene mutation. Therefore, it may
      be presumed that p53 protein accumulation can result primarily from mutation. In
      addition, stabilization of p53 through binding to other proteins is another
      possible reason of p53 overexpression.

PMID- 8996550
TI  - Effect of tumor excision on NK cytotoxic activity and formation of metastases of
      Bomirski melanoma in hamsters.
AB  - The growth of transplanted Bomirski melanoma in hamsters is accompanied by the
      decrease of natural killer cytotoxic activity and the formation of metastases.
      The excision of primary tumors was carried out to examine what was the effect of
      the growing tumor and its metastases on the host's NK activity. It was found that
      the excision of primary tumor caused increased NK cytotoxic activity in
      comparison to that of nonoperated animals although it was still lower than that
      of healthy hamsters. It is concluded that both, a growing tumor and metastases,
      exert suppressive effects on NK activity and those effects add up. The pattern of
      metastases in operated animals was different to that observed in nontreated
      hamsters.

PMID- 8996551
TI  - Biological consequences of E.coli RecA protein expression in the repair defective
      pso4-1 and rad51::URA3 mutants of S. cerevisiae after treatment with N-methyl-N'
      nitro-N-nitrosoguanidine.
AB  - RecA protein of E.coli is a multifunctional protein participating in genetic
      recombination, recombinational repair and mutagenesis. We used E.coli recA gene
      as a probe for complementation of repair defects after treatment of N-methyl-N'
      nitro-N-nitrosoguanidine in the pso4-1 and rad51::URA3 mutants of S. cerevisiae.
      We tried to find the role of the RecA protein in S. cerevisiae mutants defective
      in different repair pathways. The RecA protein had no effect on survival of
      haploid and diploid pso4-1 mutants, but it had a significant effect on MNNG
      induced mutagenesis, which was increased to the wild type level. No effect of the
      RecA protein on survival was observed in rad51::URA3 mutant after MNNG treatment.
      However, in this case the RecA protein decreased the induced mutagenesis. We can
      suppose that the RecA protein, with its multifunctional enzymatic activity, can
      bind to special intermediates and initiate function of different repair pathways
      depending on repair defects of the mutants studied.

PMID- 8996552
TI  - Serum soluble IL-2 receptor as a reliable and noninvasive marker of disease
      activity in patients with hairy cell leukemia.
AB  - Hairy cell leukemia is a chronic lymphoproliferative disorder of B-cell lineage.
      Malignant cells express the interleukin-2 receptor (IL-2R) which is released in
      vitro as well as in vivo. The sera of patients with hairy cell leukemia contain
      elevated levels of this soluble receptor (sIL-2R). Sera of 24 patients with hairy
      cell leukemia were tested for sIL-2R. In 9 patients treated with 2
      chlorodeoxyadenosine an improved clinical status was associated with decreasing
      serum sIL-2R. The maximal rate of decrease of sIL-2R level was observed within
      the second and the third week after the therapy initiation. Patients with disease
      progression had an increase in serum sIL-2R level. Our results suggest that
      serial measurement of sIL-2R level can be used as a reliable, noninvasive means
      to assess the disease activity and its response to therapy.

PMID- 8996553
TI  - The effect of local hrec TNF-alpha administration upon the spontaneous lung
      metastases in rats with Morris 5123 hepatoma.
AB  - The experiment used Morris hepatoma 5123 series growing in muscles of the right
      hind limb of Buffalo rats. The group I animals were given intratumor 4 doses of
      TNF-alpha and group II-8 doses of TNF-alpha (10 micrograms/day). Control groups
      (III and IV) consisted of rats with injected Morris hepatoma, which were given
      PBS solution instead of TNF-alpha. A decrease in the volume of neoplastic
      metastases was observed in groups I and II, compared with groups III and IV. At
      the same time an increase was found in the volume of metastatic tumors in group
      II (8 x TNF-alpha), compared with group I (4 x TNF-alpha). Histological and
      ultrastructural analysis of the pulmonary tissue revealed intensified fibrotic
      reactions and inflammatory infiltrations around the metastatic tumors. The change
      were much more enhanced in group II, which might affect the results of neoplastic
      metastatic volume measurements. We concluded that multiple human recombinant TNF
      alpha, hrec TNF-alpha, local injections inhibited dissemination of tumor cells
      and prolonged the survival time of rats up to the 76th day of the follow-up.

PMID- 8996555
TI  - Modulatory effect of tempol on toxicity and antitumor activity of 6
      mercaptopurine and on P450 cytochrome level.
AB  - Low selectivity of contemporary antitumor drugs requires a search for its
      improvement. In this context, nitroxyl radicals are of interest as promising
      pharmacological agents. The introduction of nitroxyl radical into the structure
      of antitumor cytostatics was found to reduce considerably their general and
      specific toxicity. In this work, we demonstrate a detoxifying effect of tempol
      upon its combined injection with cytostatics at their absolute lethal dose in the
      intact mice as well as an improvement of sensitivity of tumor-bearing animals to
      6-MP. Tempol is shown to normalize the level of oxidized form of P450 cytochrome
      in a liver, reduced as a result of the injection of 6-MP.

PMID- 8996554
TI  - Antitumor action of bovine seminal ribonuclease.
AB  - Unlike the bovine pancreatic ribonuclease (RNaseA), bovine seminal ribonuclease
      (BS RNase) displays various biological activities, including antitumor activity,
      immunosuppressivity, spermatogenicity and embryotoxicity. To learn more about its
      antitumor effect we tested BS RNase on the growth of 16 cell lines derived from
      patients with various hematological malignancies. The cells of lymphoid origin
      were generally more susceptible to BS RNase, administered in the range of
      concentrations from 2 to 100 micrograms/ml, than the myeloid ones. RNaseA used at
      the same concentrations did not exert any inhibitory effect. The inhibitory
      effect of BS RNase persisted in cultured cells after three times wash in complete
      medium and cell recultivation in fresh medium free of BS RNase. Four cell lines
      were very little sensitive (KG-1 and U-937) or resistant (JOK and NAMALWA) to BS
      RNase regardless of their origin. The in vivo antitumor effect of BS RNase was
      tested on human prostate carcinoma transplanted to athymic nude mice. The daily
      dose of BS RNase (0.25 mg/20 g) was administered for three weeks except weekends
      (15 doses) by three different ways (intraperitoneally-i.p., subcutaneously-s.c.
      and intratumorally-i.t.). Whereas i.p. administration was ineffective, s.c.
      administration significantly reduced size of the tumors and i.t. administration
      abolished half of the tumors in treated mice. The average weight of treated mice
      decreased during the experiment by 10-15%.

PMID- 8996557
TI  - Case-control study of pancreatic cancer in Serbia, Yugoslavia.
AB  - Case-control study comprised 100 pancreatic cancer patients and the same number
      of hospital controls individually matched with cases by sex, age and place of
      residence. According to logistic regression analysis following factors were found
      to be risk factors for pancreatic cancer: smoking 26 or more cigarettes per day
      (OR = 43.95, 95% CI = 7.69-192.53), consumption of 5 or more glasses of hard
      drinks per week (OR = 12.84, 95% CI = 2.13-77.29), coffee consumption during a
      period exceeding 35 years (OR = 2.50, 95% CI = 1.18-5.28), gall bladder disease
      in personal history (OR = 4.29, 95% CI = 1.08-16.99) and family history positive
      on peptic ulcer (OR = 11.71, 95% CI = 0.99-137.98). Two factors appeared to be
      protective for cancer of pancreas: appendectomy (OR = 0.22, 95% CI = 0.07-0.68)
      and blood type 0, Rh+ (OR = 0.25, 95% CI = 0.09-0.61).

PMID- 8996556
TI  - Phase I/II trial of carboplatin dose escalation in combination chemotherapy with
      etoposide, bleomycin and GM-CSF support for poor prognosis nonseminomatous germ
      cell tumors patients.
AB  - To determine the maximum tolerated dose (MTD), and therapeutic efficacy of
      carboplatin (CBDCA) in combination with etoposide and bleomycin (CEB) as initial
      chemotherapy for poor prognosis germ cell tumors, a CBDCA dose escalation
      supported with GM-CSF had been performed. Twenty four untreated patients were
      treated with CBDCA 400 mg/m2 on day 1, etoposide 100 mg/m2 on days 1 to 5 and
      bleomycin 30 mg on days 1, 3, 5. Four cycles were scheduled at 21-day interval.
      The first cohort of 6 patients received only initial chemotherapy regimen. In the
      subsequent cohorts of six patients, the CBDCA dose was increased by 100 mg/m2. A
      fixed dose and schedule of GM-CSF at 5 micrograms/kg subcutaneously was given on
      days 6 through 15. Myelosuppression, with neutropenic fever and hemorrhages, was
      the dose-limiting toxicity at the 600 mg/m2 dose level. The recommended dose of
      CBDCA is 500 mg/m2. Overall complete response (CR) rate was 71% and with median
      follow up of 25 (16-34) months, 58% of patients are alive and have no evidence of
      disease (NED). A higher number of CR was achieved with CBDCA dose higher than 400
      mg/m2 compared with CBDCA dose of 400 mg/m2 (92 vs. 50%, p = 0.03), as well as a
      higher proportion of patients who are alive and with NED (75 vs. 42%, p = 0.1).
      Despite GM-CSF support, the MTD of CBDCA could not be increased beyond 500 mg/m2
      (50% of the dose escalation), due to severe myelosuppression. The treatment
      outcomes obtained with CEB in our study are no better than the standard cisplatin
      based chemotherapy. Further studies of this regimen, where CBDCA dose should be
      calculated according to the patients glomerular filtration rate are warranted.

PMID- 8996558
TI  - Placental isoferritin-associated p43 in pregnancy and breast cancer. Minireview.
AB  - Ferritin, physiologically an iron-storage protein, has been repeatedly
      investigated with regard to its role in the development of inflammation and
      malignancy [2, 3, 6]. The structural heterogeneity of this protein has aroused
      considerable interest in recent years [2, 3, 5, 6]. Although ferritin is
      generally regarded as an iron-storage protein, small amounts are also found in
      the sera of normal individuals, while abnormally high concentrations are found in
      the serum of patients with malignancies as well as in pregnant women. In the
      past, considerable attention has also been paid to the structural heterogeneity
      of ferritin derived from various organs and malignant tissues [3, 5]. It has been
      reported that the placenta, fetal tissues and malignant tissues contain acidic
      ferritin, while the liver and the spleen contain ferritin in the basic form. The
      acidic isoform has been summarized under the term oncofetal ferritin, since these
      forms share certain physical-chemical characteristics. These so-called oncofetal
      or placental ferritins (PLF) have repeatedly been shown to have an inhibitory
      effect on hematopoiesis and T-cell function [2, 6, 7, 10]. The purpose of the
      present review is to elucidate current data concerning the role of placental
      isoferritin in pregnancy as well as in the development of breast cancer.

PMID- 8996559
TI  - Immunosuppressive activity of lymphocyte mitogenesis by breast cancer-associated
      p43.
AB  - Placental isoferritin (PLF), an acidic isoform of ferritin, and its unique
      superheavy chain of 43 kDa (p43) has been described to be synthesized by human
      breast cancer cells. Physiologically, p43 PLF produced by the placenta is
      involved in immune suppression of maternal lymphocytes aimed at fetal antigens. A
      study was carried out to elucidate a paradigm of p43 occurrence in breast cancer
      patients. Immunosuppression of cytotoxic CD8+ lymphocytes was measured via
      inhibition of blast transformation in concanavalin A (ConA) stimulated peripheral
      blood lymphocytes (PBL) using 3H-thymidine uptake in vitro. PBLs were cultivated
      from 29 women having benign lesions in the breast as well as from 41 patients
      with breast adenocarcinoma. In breast cancer patients addition of p43
      significantly inhibited the activation of lymphocytes proliferation by ConA
      compared to women with benign tumors. The addition of indomethacin or levamisole
      did not influence this inhibitory effect of p43 in breast cancer patients.
      Presence of interleukin-2 in cultures was able to overcome the inhibitory effect
      of p43 on CD8+ lymphocytes proliferation from women having breast adenocarcinomas
      and to increase its value in patients with benign lesions.

PMID- 8996560
TI  - Leukemia-associated phenotypes: their characteristics and incidence in acute
      leukemia.
AB  - Leukemia-associated phenotypes have been suggested to be a valuable tool for the
      detection of minimal residual disease in acute leukemia patients, as they allow
      to distinguish leukemic blasts from normal hematopoietic progenitor cells. The
      aim of the present study was to analyze the proportion of acute leukemia patients
      (both with lymphoid and myeloid leukemias) in which the immunological detection
      of leukemia-associated phenotypes was convenient for the distinction of leukemic
      and normal cells. For this purpose we have studied the blast cells from 186 acute
      leukemia patients at diagnosis with a large panel of monoclonal antibodies by
      flow cytometry using double staining combinations. From aberrant phenotypes on
      blast cells we followed lineage infidelity (coexpression of myeloid markers in
      lymphoid leukemia cells and vice versa, as well as the simultaneous expression of
      both, T and B cell markers in one lymphoid blast cell) and asynchronous marker
      expression (simultaneous expression of early and late markers in one cell). One
      hundred and five of the 186 acute leukemia cases analyzed (56%) showed the
      presence of leukemia-associated phenotypes. In 41 of the 90 ALL cases followed
      (46%) and in 40 of the 96 AML cases studied (42%) lineage infidelity was
      observed. Asynchronous antigen expression was detected in 24 followed cases
      (13%). Evaluation of the cell marker density by means of calibration microbeads
      demonstrated abnormal mean channel immunofluorescence and molecules of equivalent
      soluble fluorescein for CD8 in two patients with T cell malignancies at
      diagnosis. Abnormal CD8 density might thus represent a characteristic feature of
      malignant CD8-positive T cell clone. Quantitative marker evaluation therefore
      seems to be another important mean for the detection of aberrant phenotypes on
      leukemia cells suitable for the detection of minimal residual disease.

PMID- 8996561
TI  - Some early differentiation markers detected in cytoplasm of pre-B cells by flow
      cytometry.
AB  - Immunofluorescent staining of cytoplasmic IgM (heavy chains) and CD24 as well as
      their simultaneous staining with surface B cell markers was used to study
      immunophenotype changes in B cell differentiation. Human hematopoietic B cell
      lines P3HR1 and RAJI were used. We found that IgM and CD24 cell markers while
      absent on cell membrane could be detected in their cytoplasm (c). The presence of
      cIgM in cell lines RAJI, P3HRI indicates their early pre-B differentiation stage.
      The presence of cCD24 simultaneously with mCD22 and cIgM is the evidence that
      hematopoietic cell lines or leukemias may not accurately reflect normal
      differentiation pathway. Combinations of cIgM, cCD24 with surface B cell markers
      CD10, CD19 on these cell lines can be considered as leukemia associated
      phenotypes. Some of them were shown in bone marrow and peripheral blood of pre-B
      ALL and B-CLL patients and can be used for the detection of minimal residual
      disease. Different fixation/permeabilization methods were tested in order to
      choose the optimal one for simple detection of cytoplasmic markers or their
      simultaneous detection with surface markers by flow cytometry. They included "one
      component-methods" (methanol-M, saponin-S), methods combining these components
      with paraformaldehyde (P+M, P+S) or buffered formaldehyde acetone (BFA). The
      choice depended on individual marker detected. General parameters like the
      proportion of debris, cell aggregation, cell loss and the changes of scatter
      parameters FSC and SSC were taken into consideration. The priorities of combined
      methods P+S, P+M1 and BFA over one-component methods are demonstrated.

PMID- 8996562
TI  - Flow cytometric detection of some activation and proliferation markers in human
      hematopoietic cell lines.
AB  - Simultaneous surface marker/DNA, cytoplasmic/DNA or nuclear/DNA staining was used
      to study proliferation of hematopoietic cell lines (MOLT4, BJAB, P3HR1).
      Different fixation/permeabilization methods (paraformaldehyde with metanol or
      Tween 20 or saponin, buffered formaldehyde-acetone) were used providing optimal
      results of the double stainings. There was a significant increase of S phase and
      proliferation index (PI) of CD71+ and Ki67+ MOLT4 cells in comparison with their
      negative counterparts. This indicates their close connection with proliferation.
      Unlike that, the correlation between the expression of CD38 and S phase or PI was
      not significant either in MOLT4 or in P3HRI cells. For cytoplasmic markers CD3
      (in MOLT4 cells) and CD22 (in BJAB cells) statistically significant (cCD3) and
      not significant (cCD22) correlation was demonstrated between their expression and
      S phase or PI. Molecular equivalents of soluble fluorescein values for CD71 were
      always higher than for CD38. The density of these cell surface markers in
      addition to the percentage of their expression is of considerable significance
      for their evaluation as activation or proliferation markers.

PMID- 8996563
TI  - Cell surface phenotype and increased penetration of human multidrug-resistant
      ovarian carcinoma cells into in vitro collagen-fibroblasts matrix.
AB  - Human multidrug resistant ovarian carcinoma cells (A2780/ADR) exhibited increased
      in vitro penetration into the collagen-normal human fibroblasts matrix, increased
      cell surface expression of alpha 6 integrin (CD49f antigen) and slightly
      increased expression of alpha 2 (CD49b) integrin compared with that of parental
      drug-sensitive A2780 cells. Both, multidrug-resistant and parental, drug
      sensitive, cell lines did not express the 67 kDa non-integrin high affinity
      laminin receptor on their cell surfaces. As there were no marked differences
      between metalloproteinase activity of both A2780 cell sublines (with similar
      intensity of 72 kDa and 92 kDa lysis bands in zymograms), the increased
      penetration of the drug-resistant subline into the collagen-fibroblast gel matrix
      might be associated with the increased expression of adhesion proteins (including
      collagen-binding alpha 2 integrin), or cell surface-associated collagenase
      stimulating protein(s). This multidrug resistant ovarian carcinoma cell line
      might serve as an in vitro model of neoplastic cells with increased biological
      aggressiveness, molecular mechanisms of which require further analysis.

PMID- 8996564
TI  - The study of AgNOR proteins in leukemias: diagnostic value and correlation to S
      phase cell fraction.
AB  - The study assessed the diagnostic value of silver staining method and its
      possible relevance as an alternative to DNA analysis for the study of cellular
      proliferation in various leukemias (ALL, AML, CML). Silver staining of nucleolar
      organizer region-related proteins (AgNORs) was applied to peripheral blood and
      bone marrow cells. The analysis of S-phase cells was carried out using a FACStar
      flow cytometer. The mean number of AgNOR dots per nucleus and the percentage of S
      phase cells varied according to immunophenotype of leukemic cells, depending on
      the time of initial diagnosis, remission or relapse. Peripheral blood and bone
      marrow cells of healthy subjects exhibited less AgNOR dots than leukemic cells.
      The number of AgNORs in bone marrow cells was higher than that of AgNORs in
      peripheral blood. Significant differences between ALL and AML, as well as AML and
      CML in AgNOR quantity were observed. Important increase in AgNOR values was
      evident in relapsed leukemias and in the CML blast crisis. DNA flow cytometry
      analyses provided results comparable to those of AgNOR enumeration. The
      correlation between AgNOR dots and proportion of S-phase cells prompted us to
      consider that AgNOR count reflects cell proliferation capacity of leukemic cells.

PMID- 8996565
TI  - Potential carcinogenicity of the synthetic 1,3,6-triazine (6-aza) nucleic acid
      analogues determined by DC polarography. I. Nucleobases.
AB  - The polarographic reduction of several synthetic 1,3,6-triazine (6-aza)
      nucleobases in the strictly anhydrous solution was studied in the absence and
      presence of alpha-lipoic acid. The values of the half-wave potentials E1/2 and
      the parameter of potential carcinogenicity tg alpha were determined for one
      natural and 5 synthetic nucleobases. The current value of the first diffuse
      polarographic wave or a new diffuse polarographic wave belonging to the
      nucleobase-alpha-lipoic acid complex increased with the increased alpha-lipoic
      acid concentration for the all compounds only marginally. Although this diffuse
      current increase was linearly depended on the alpha-lipoic acid concentration in
      anhydrous solutions, the determined index tg alpha values ranging between 0.029
      and 0.108 indicated a very low potential carcinogenicity of the all nucleobases
      investigated.

PMID- 8996566
TI  - Comparison of the in vitro effect of adriblastina on induction of SCEs in V79
      cells and human peripheral blood lymphocytes.
AB  - Induction of sister chromatid exchanges (SCEs) by the cytotoxic antibiotic
      adriblastina (doxorubicin, 14-hydroxyrubidomycin) of the anthracycline group
      isolated from Streptomyces peucetius var. caesius by Farmitalia Research
      Laboratories was tested in vitro at concentrations of 0.01 microgram/ml, 0.1
      microgram/ml and 0.2 microgram/ml using V79 cells and human peripheral blood
      lymphocytes from healthy donors. In comparison with negative control,
      adriblastina significantly elevated the SCE frequency both in V79 cells and in
      human peripheral blood lymphocytes. The results obtained by comparing the effect
      of equivalent adriblastina concentrations on V79 cells and human peripheral blood
      lymphocytes showed no significant difference in the mutagenicity effect of both
      of these cell lines to adriblastina.

PMID- 8996567
TI  - Approaches to prove the melanoma origin in amelanotic human melanoma cell lines.
AB  - The human melanoma B-HM8 cell line was derived from highly pigmented malignant
      skin melanoma. After 5 weeks of cultivation it entirely lost the pigmentation and
      has remained amelanotic since. Electron microscopy revealed neither
      premelanosomes nor melanosomes and the cells did not release detectable amount of
      dopa-oxidase activity into culture medium. Immunocytochemical studies using the
      polyclonal anti-S-100 antibody and detection of alpha-mannosidase activity in
      culture medium proved the melanoma origin of B-HM8 cells. Chromosomal changes in
      the karyotype of these cells were typical for human melanoma with chromosomes No.
      1, 5, 7, 9, and 11 involved most frequently.

PMID- 8996568
TI  - Protective effects of cardioxane against anthracycline-induced cardiotoxicity in
      relapsed acute myeloid leukemias.
AB  - The clinical use of anthracyclines and related antitumor agents is limited by
      their cumulative dose-related cardiac toxicity. Cardioxane (ICRF-187) is an agent
      that has been recommended to block selectively this toxicity which e.g. limits
      the use of daunorubicin (DNR) in doses higher than 550-700 mg/m2. We decided to
      use cardioxane in patients with relapsed acute myeloid leukemias (AML) who have
      previously been treated with DNR doses above 500 mg/m2. Seven patients with
      relapsed AML received cardioxane 30 min before DNR or mitozantrone (MTZ) in doses
      8-13x higher than DNR or 40-60x higher than MTZ. Two patients received
      anthracyclines cumulative doses corresponding to more than 1300 mg/m2 and 1000
      mg/m2 of DNR, respectively, without any signs of cardiac toxicity. The other 5AML
      patients in relapse received 1-3 chemotherapy cycles with cardioxane. Their total
      cumulative doses of DNR were 550-750 mg/m2 and their left ventricular ejection
      fraction remained above 50% as were their pretreatment values. Cardioxane seems
      to be a useful cardioprotective agent in relapsed AML which enables further
      treatment with anthracyclines.

PMID- 8996569
TI  - Etoposide phosphate: what, why, where, and how?
AB  - The podophyllotoxin derivatives etoposide and teniposide are active in the
      treatment of a variety of malignant conditions. Both represent chemical
      modifications of podophyllin, an extract of Podophyllum peltatum (May apple,
      mandrake, Indian apple, wild lemon, or duck's foot), a plant long used as a folk
      remedy and recognized in the 19th century to be effective in the treatment of
      cancer. While etoposide is active in the treatment of many cancers and is widely
      used, it has a number of limitations due to its lack of water solubility.
      Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a
      water-soluble prodrug of etoposide that is rapidly and completely converted to
      the parent compound after intravenous dosing. The pharmacokinetic profile of
      etoposide after treatment with either etoposide or etoposide phosphate is
      identical. Toxicity and clinical activity also are the same. Because etoposide
      phosphate is water soluble and can be made up to a concentration of 20 mg/mL,
      however, it can be given as a 5-minute bolus, in high doses in small volumes, and
      as a continuous infusion. Furthermore, it is not formulated with polyethylene
      glycol, polysorbate 80 (Tween; ICI Americas, Wilmington, DE), and ethanol, and
      does not cause acidosis when given at high doses. The easier-to-use etoposide
      phosphate represents an improved formulation of etoposide.

PMID- 8996570
TI  - Early studies of etoposide phosphate, a water-soluble prodrug.
AB  - Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a
      water-soluble prodrug of etoposide that is converted in vivo by endogenous
      phosphatases to the active drug etoposide. This conversion process is efficient
      and not saturable in humans at doses between 50 and 1,600 mg/m2. The resultant
      etoposide demonstrates classic pharmacokinetics, and the etoposide phosphates
      dose is linearly related to peak levels and the area under the concentration-time
      curve of etoposide. The absence of noxious solvents and the ability to administer
      the drug in small volumes over short periods make etoposide a phosphate
      attractive for conventional- and high-dose clinical programs.

PMID- 8996571
TI  - A pharmacodynamic evaluation of hematologic toxicity observed with etoposide
      phosphate in the treatment of cancer patients.
AB  - The pharmacodynamics of etoposide phosphate (Etopophos; Bristol-Myers Squibb
      Company, Princeton, NJ), a water-soluble prodrug of etoposide, was evaluated in
      39 patients with solid tumors after a 30-minute intravenous infusion of
      escalating doses (equivalent to 50 to 175 mg/m2 of etoposide) on a day 1, 3, and
      5 schedule of treatment. Serial blood samples were collected at predose and
      throughout the 32 hours following day 1 of treatment to determine the area under
      the plasma concentration-time curve (AUC) of etoposide phosphate and etoposide.
      Hematology profiles and serum chemistries were determined at predose and twice
      weekly for approximately 3 weeks after each treatment cycle. Both linear and
      nonlinear pharmacodynamic models were used to evaluate the relationship between
      hematologic toxicity and etoposide AUC and patient factors (age, gender,
      performance status, prior radiation therapy, prior chemotherapy, baseline
      albumin, bilirubin, alkaline phosphatase, creatinine, leukocyte count,
      granulocyte count). Etoposide phosphate was converted rapidly to etoposide in
      vivo. The ratio of the etoposide phosphate AUC to that of etoposide was < or =
      1.2% indicating that etoposide was the main species in the systemic circulation.
      Myelosuppression was the dose-limiting toxicity, and significant decreases in
      white blood cell and granulocyte counts were noted. Hematologic toxicity was best
      described by a stepwise linear regression model consisting of etoposide AUC,
      serum albumin, and bilirubin. In summary, hematologic toxicity produced by the
      intravenous administration of etoposide phosphate correlates significantly with
      etoposide AUC and patient factors (baseline serum albumin and bilirubin) in
      cancer patients.

PMID- 8996572
TI  - Effects of gender, age, and race on the pharmacokinetics of etoposide after
      intravenous administration of etoposide phosphate in cancer patients.
AB  - The influence of gender, age, and race on the pharmacokinetics of etoposide and
      on the extent of conversion of etoposide phosphate (Etopophos; Bristol-Myers
      Squibb Company, Princeton, NJ) to etoposide are summarized. Included in the
      integrated statistical analyses were 192 patients from six phase I/II studies
      (102 men and 90 women, 128 aged < or = 65 years and 64 aged > 65 years; 134 were
      white, 18 were other races, and race was not recorded for 40). The dose of
      etoposide phosphate ranged from 25 to 200 mg/m2 of etoposide equivalents and was
      administered as 5-(bolus) to 210-minute intravenous infusions. Total body
      clearance of etoposide was comparable between men and women. However,
      significantly lower steady-state volumes of distribution and shorter half-lives
      were observed in women relative to men. Patients who were older than 65 years had
      significantly lower etoposide total body clearance and longer half-lives than
      younger patients. The gender- and age-related differences observed in the
      pharmacokinetic parameters of etoposide were significant but generally of a small
      magnitude (< or = 13%), indicating no need for dose adjustment in these patient
      populations. There were no significant race-related differences in the
      pharmacokinetic parameters of etoposide. All patients showed rapid conversion of
      etoposide phosphate to etoposide. The individual area under the plasma
      concentration-time curve ratio of etoposide phosphate/etoposide was < or =
      0.0324, indicating that etoposide was the major circulating moiety after infusion
      of etoposide phosphate. Significant gender-, age-, or race-related differences in
      the area under the plasma concentration-time curve ratios were not observed. An
      evaluation of the area under the plasma concentration-time curve ratios with
      respect to infusion time suggested that the conversion of etoposide phosphate to
      etoposide was independent of infusion time.

PMID- 8996573
TI  - A phase I study of etoposide phosphate plus paclitaxel.
AB  - Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a
      water-soluble derivative of etoposide, a semisynthetic podophyllotoxin that is
      important in the treatment of a variety of malignancies, including lung cancer,
      germ cell tumors, non-Hodgkin's lymphoma, Hodgkin's lymphoma, acute leukemia,
      etc. Because etoposide is poorly water soluble, it must be dissolved in a
      polysorbate 80-based solvent mixture, which is moderately allergenic and requires
      a large volume of saline for administration. Etoposide phosphate is water soluble
      and is rapidly converted in vivo to etoposide by endogenous phosphatases. Because
      it is water soluble, etoposide phosphate can be administered in volumes much
      smaller than those required with etoposide therapy, permitting rapid intravenous
      administration in the outpatient setting. We recently reported the results of a
      phase I study using etoposide phosphate on a bolus, daily x 5 schedule. Like
      others, we demonstrated that etoposide phosphate has pharmacokinetic properties
      virtually identical to those of etoposide. Our dose-finding study indicated that
      etoposide phosphate can be used in doses up to 100 mg/m2/d x 5 every 3 weeks in
      patients who have not had extensive prior chemotherapy, and that a dose of 75
      mg/m2 would be appropriate for patients who had undergone multiple prior
      therapies or who had prior radiotherapy. The dose-limiting toxicity was
      neutropenia. Paclitaxel, a microtubule-stabilizing agent, is active against a
      variety of solid and hematopoietic malignancies that overlap with those against
      which etoposide is active. Because the mechanisms of action of these two agents
      differ, it is logical to suppose that the combination of the two agents might
      produce some additive effect when used to treat cancers that respond to both
      individual agents. We therefore undertook a phase I study using paclitaxel as a 3
      hour infusion in combination with a 5-minute infusion of etoposide phosphate
      daily x 3 every 21 days. We used the 3-hour paclitaxel schedule because it has
      been shown to be less myelotoxic than longer infusions at the same doses. Our
      goal in this ongoing study is to determine the maximum tolerated doses of the two
      drugs in combination, to determine the toxicities of the regimen, and to assess
      its anticancer activity.

PMID- 8996574
TI  - Etoposide phosphate infusion with therapeutic drug monitoring in combination with
      carboplatin dosed by area under the curve: a cancer research campaign phase I/II
      committee study.
AB  - The area under the plasma concentration-time curve (AUC) following an intravenous
      dose of etoposide varies considerably among patients, which in part contributes
      to the unpredictability of toxicity and response seen in individual patients.
      This study evaluated the utility of therapeutic drug monitoring of etoposide in
      reducing the interpatient variability of etoposide steady-state concentrations
      during prolonged infusion. The etoposide prodrug etoposide phosphate (Etopophos;
      Bristol-Myers Squibb Company, Princeton, NJ) was administered by infusion using
      an adaptive dosing strategy. It was given in combination with carboplatin, which
      was dosed on an AUC basis. Patients with histologically or cytologically proven
      small cell lung cancer were treated with etoposide phosphate by continuous 120
      hour infusion and carboplatin at a dose calculated by the Calvert formula to give
      an AUC of 5 mg/ mL.min. Blood samples were taken on days 2 through 5 of each
      treatment cycle, and high-performance liquid chromatography was used to measure
      the plasma etoposide concentration. The resultant concentrations were compared
      with target concentrations of 1 or 2 micrograms/mL and these data were used to
      calculate the rate of infusion for the following 24 hours. In the first cohort,
      the target etoposide concentration was 1 microgram/mL, and this was achieved
      (mean +/- SD = 1.05 +/- 0.24 micrograms/mL) by infusing etoposide phosphate doses
      of 21 to 109 mg (15 to 68 mg/m2) per day. In the second cohort, the target
      concentration of 2.0 micrograms/mL was achieved (mean +/- SD = 2.05 +/- 0.31
      micrograms/mL) with infused etoposide phosphate doses of 69 to 193 mg (41 to 114
      mg/m2) per day. This technique reduced the variation in plasma levels and
      resulted in predictable hematologic toxicity. Cumulative hematologic toxicity
      necessitated an extension of the treatment cycle from 3 to 4 weeks, however. Of
      six evaluable patients, two had a complete response and one had a partial
      response. Therapeutic drug monitoring was shown to reduce the interpatient
      variation in the plasma etoposide concentration by half and shows promise for
      individualizing treatment with combination chemotherapy. Exploiting the known
      relationships between the pharmacokinetics and pharmacodynamics of these two
      drugs by using therapeutic drug monitoring may lead to better therapeutic safety
      and efficacy.

PMID- 8996575
TI  - Clinical studies with etoposide phosphate.
AB  - Over the past few years we have conducted several clinical studies with etoposide
      phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ). A phase I
      trial initially was performed to determine the maximum tolerated dose and
      pharmacokinetics. A brief intravenous infusion for 5 consecutive days was given
      every 3 weeks. Myelosuppression was the dose-limiting toxicity and other
      toxicities were quite similar to those associated with etoposide. The maximum
      tolerated dose was 100 mg/m2/d for 5 consecutive days. No cytokine support was
      used in this phase I trial. Pharmacokinetic studies showed very rapid conversion
      of etoposide phosphate to etoposide. The kinetics of etoposide phosphate were
      similar to those expected after a comparable etoposide dose. We subsequently
      began three additional studies, including a phase II randomized comparison of
      etoposide phosphate plus cisplatin versus etoposide plus cisplatin in patients
      with small cell lung cancer, a study of low-dose continuous infusion daily
      etoposide phosphate, and a high-dose etoposide phosphate trial to determine the
      maximum tolerated dose given in concert with granulocyte colony-stimulating
      factor. The latter two studies are complete; these data are currently being
      evaluated. The phase II comparative trial was important and showed unequivocally
      that the response rate and toxicity with etoposide phosphate plus cisplatin is
      equivalent to those with etoposide plus cisplatin in patients with small cell
      lung cancer. In addition, it appears that there was no survival difference
      between these two treatment arms in this phase II trial of 120 patients.
      Etoposide phosphate is easier to administer than etoposide and, considering all
      other factors, including total cost of administration, it is preferable to
      etoposide for routine clinical use.

PMID- 8996576
TI  - A pharmacoeconomic evaluation of cisplatin in combination with either etoposide
      or etoposide phosphate in small cell lung cancer.
AB  - To compare etoposide and etoposide phosphate (Etopophos; Bristol-Myers Squibb
      Company, Princeton, NJ) in maximizing the cost efficiency of care for patients
      with small cell lung cancer (SCLC), we obtained pharmacoeconomic data from a
      phase II randomized study of these agents. This clinical investigation assessed
      the efficacy and toxicity of etoposide phosphate combined with cisplatin in
      treating SCLC. In the economic analysis, we identified resources expended during
      chemotherapy and related concomitant procedures and matched them with the current
      procedure terminology level of costs for the provider and the payor. The
      valuation process was conducted in the specific point-of-care (outpatient v
      inpatient) setting. The appropriate pharmacoeconomic analytic tool used when
      comparators are considered to achieve equivalent clinical outcomes is cost
      minimization analysis. We provide the cost-minimization analysis from two
      oncology care perspectives: the provider and the payor. In addition, a payor/
      provider cost reduction model was constructed to illustrate the potential
      economic effects achieved through more efficient use of the outpatient
      chemotherapy facility due to the ease of administration of etoposide phosphate.
      The provider's average cost per patient for treating an SCLC patient for six
      cycles in US dollars is $26,764.48 for etoposide versus $26,026.70 for etoposide
      phosphate. The payor's average treatment cost per patient for treating an SCLC
      patient for six cycles for the respective regimens was $34,270.65 and $34,320.70.
      When the time savings associated with the etoposide phosphate regimen are applied
      to the outpatient chemotherapy facility, the adjusted average treatment costs per
      patient for the payor are $2,797.29 less than the costs for using the standard
      etoposide intravenous formulation. Delivering an etoposide phosphate regimen
      accrued adjusted savings of $2,897.03 per patient. Based on these results,
      etoposide phosphate is a superior pharmacoeconomic alternative compared with
      standard etoposide chemotherapy in managing SCLC. The potential increase in
      patient volume conferred by the relative simplicity of etoposide phosphate
      administration would have a significant impact on operations in terms of
      scheduling patients and staff and increasing operational efficiencies, thereby
      facilitating cost reductions in excess of $2,700 per patient when an etoposide
      phosphate regimen is chosen over an etoposide regimen.

PMID- 8996577
TI  - Highlights of abstracts on hormone-refractory prostate cancer presented at the
      1996 annual meeting of the American Society of Clinical Oncology.
AB  - Among the more interesting studies at the 1996 annual meeting of the American
      Society of Clinical Oncology that related to hormone-refractory prostate cancer
      were several that reported on the use of cis-retinoic acid both alone and in
      combination with interferon-alpha. Interferon-alpha and interferon-alpha plus cis
      retinoic acid have antiproliferative effects in vitro against both PC3 and D-145
      prostate cancer cells in culture. BCL2 expression is increased in androgen
      independent cells, which may block apoptosis, and retinoids induce transforming
      growth factor-beta and apoptosis in prostate cancer cell lines. This regimen
      raises many questions. For example, it is difficult to determine what prostate
      specific antigen (PSA) level one should expect from cis-retinoic acid, 4HPR, or
      any of the other differentiating agents. Should there be an increase in PSA1
      Should one expect a slower decline in PSA when giving additional agents that are
      in fact cytotoxic? What is the significance of a changing level of PSA after this
      and other types of treatment? These and other questions remain to be determined
      in future studies.

PMID- 8996578
TI  - Clinical use of posttherapy prostate-specific antigen changes in advanced
      prostate cancer.
AB  - Posttherapy changes in prostate-specific antigen (PSA) have been used as a
      primary endpoint for patients with prostate cancer in an effort to rapidly
      identify promising therapeutic approaches. Using this method, agents that do not
      produce a defined decline in PSA on multiple determinations for a specified
      period are not to be pursued further. Multiple investigators have used PSA as an
      outcome measure, but the results are variable and often difficult to interpret.
      These inconsistencies are due to the lack of a consensus on criteria for PSA
      declines and the inappropriate use of PSA as an and point when it is not
      clinically applicable. Phase III studies are needed to validate any surrogate
      variable, including posttherapy declines in PSA; until such trials have been
      performed, investigators need to define and report all parameters of outcome
      independently.

PMID- 8996579
TI  - Overview of Canadian trials in hormonally resistant prostate cancer.
AB  - There is no consensus about the best systemic treatment for hormonally resistant
      prostate cancer. Several regimens have been examined; none of them have
      demonstrated a consistent increase in overall survival. The treatment of
      hormonally resistant prostate cancer is therefore palliative. Recent studies in
      Canada have taken the approach that the best way to measure disease palliation is
      to assess the effects of therapy on disease-related symptoms and quality of life.
      Studies with mitoxantrone and prednisone confirm that this regimen is well
      tolerated and leads to symptomatic improvement in approximately 40% of patients,
      with a median duration of improvement of more than 10 months. This is greater
      than that achieved with prednisone alone. Treatments that have greater activity
      against hormonally resistant disease are urgently needed, although improvements
      probably will be gradual and modest. While it may be appealing to intensity
      treatments to obtain greater efficacy, there is a real risk that the toxicity
      will nullify any benefits. This approach of directly measuring the ability of
      systemic therapies to provide palliation is an appropriate way to assess newer
      therapies for hormonally resistant prostate cancer.

PMID- 8996580
TI  - Management of hormone-resistant prostate cancer: an Australian trial.
AB  - The management of metastatic prostate cancer that has relapsed after initial
      hormonal manipulation remains a major problem, with the majority of patients
      dying within 12 months. Their clinical course is frequently characterized by
      progressive debilitation, pain, and other tumor-related symptoms. A phase II, non
      randomized multicenter clinical trial was carried out in Australia in 1985-1986
      to assess the efficacy and toxicity of mitoxantrone. Substantial anticancer
      activity was shown against hormone-refractory prostate cancer, indicated by
      reduction in tumor-related symptoms, improvement in quality of life indices, and
      a median survival of 10 months in patients with a heavy tumor burden. Although it
      is not possible to equate this nonrandomized series more fully with current
      experience since routine prostate-specific antigen measurement was not performed,
      the median survival of 10 months was equivalent to or better than the survival
      times reported from most other institutional reports of the time. Even more
      importantly, however, major improvements were noted in such subjective indices as
      reduction in pain, weight gain, and performance status. Toxicity was also
      acceptable, with the major side effect being asymptomatic myelosuppression.

PMID- 8996582
TI  - Cancer and Leukemia Group B trials for advanced prostate cancer.
AB  - The approach to treatment for advanced prostate cancer patients who have failed
      to respond to therapy with androgen deprivation has undergone a significant and
      fundamental transformation over the last 3 years, beginning with the description
      of the flutamide-withdrawal syndrome in 1993. This was the same year that the
      Cancer and Leukemia Group B Prostate Cancer Committee was created. This committee
      has been studying the following two important areas in advanced prostate cancer
      the optimal treatment and biology of androgen-independent, yet hormonally
      sensitive, prostate cancer; and the optimal treatment for patients with truly
      hormone-refractory disease. Important biologic and quality of life correlative
      trials will complement the clinical information gained, with the goal of
      providing further insight into the extremely complex biological processes
      involved.

PMID- 8996581
TI  - Southwest Oncology Group studies in hormone-refractory prostate cancer.
AB  - Virtually all patients with hormone-refractory prostate cancer will eventually
      succumb to their diseases with no demonstrable increase in survival with any
      second-line therapy, thus making the conventional approach to the treatment of
      this disease palliative. The Southwest Oncology Group (SWOG) Genitourinary
      Committee strategy in investigating therapy for hormone-refractory prostate
      cancer is focused on the application of biologically guided treatments targeting
      primary patients with limited prior hormonal therapy, taking into account
      evolving concepts regarding the definitions of "hormone-refractory" disease and
      response criteria. This report reviews data from selected SWOG studies conducted
      in the past 10 years, and outlines the rationale and design of current and future
      studies conducted by the Genitourinary Committee of the SWOG in hormone
      refractory prostate cancer.

PMID- 8996583
TI  - Quality of life in advanced prostate cancer.
AB  - Palliation is the principal aim of treatment for patients with advanced prostate
      cancer. In a strict sense, "palliation" means reduction of existing symptoms, but
      in clinical practice a further goal is to prolong the symptom-free interval in
      asymptomatic patients and to prevent distressing problems, such as pain and
      fatigue, with the overall aim of improving quality of life. In patients with
      advanced prostate cancer, quality of life parameters represent an important
      endpoint in clinical routine and in clinical trials. Evaluation of quality of
      life issues also provides independent prognostic information. A feasible approach
      for regular quality of life assessment is the use of a questionnaire developed
      for cancer patients together with psychometrically tested disease-specific and
      treatment-specific modules designed to evaluate the various factors, such as
      micturition, sexuality, vitality, and intestinal problems for localized prostate
      cancer, and bone pain, micturition, sexuality, hot flashes, gynecomastia, and
      gastrointestinal problems for metastatic prostate cancer.

PMID- 8996584
TI  - Preclinical models of prostate cancer.
AB  - Prostate cancer is the most common non-skin malignancy, yet the biological and
      molecular characteristics of the disease remain only poorly understood. One of
      the many reasons for this is that there are so few animal or human laboratory
      models of prostate cancer. Prostate cancer rarely arises spontaneously in
      animals, and the human cancer is unusually hard to grow in culture or as
      xenografts even short-term. The prostate cancer models that do exist are
      basically rodent models, human cell lines, human xenografts, and gene transfer
      and transgenic models. Many laboratories have put great effort into developing
      prostate cancer models, without much success. These efforts recently have been
      forced to be curtailed, primarily due to a lack of funding. There is good reason
      to believe, however, that propagation of metastatic tissue will be much more
      successful. At the University of Washington, the Prostate Cancer Donor Program,
      organized in a manner similar to existing methods for cadaver organ harvest, has
      been instituted to help recruit patients for these approaches. Prospects for
      success of model development also have been improved because of advances in
      techniques for the maintenance of severe combined immunodeficiency disease mice
      or nude mice.

PMID- 8996585
TI  - Targeted therapy for prostate cancer: the Memorial Sloan-Kettering Cancer Center
      approach.
AB  - Carcinoma of the prostate represents a wide range of diseases with differing
      prognoses. A key to selecting treatment depends on the ability to predict the
      natural history of the disease for the individual. Thus far, non-hormonal
      approaches have not demonstrated a survival advantage in randomized comparisons
      and, clearly, innovative approaches are needed. The clinical trials program
      developed at Memorial Sloan-Kettering Cancer Center is based on specific
      manifestations and specific targets of the disease and the predicted prognosis,
      using prostate-specific antigen and acid phosphatase changes as biomarkers of
      progression and response. In patients with minimal disease who have received
      local treatments but progressed systemically, we are studying methods aimed at
      stimulating their immune systems either by nonspecific immunopotentiation or
      specific immunization to specific glycoprotein or carbohydrate targets on the
      cancer cells, or to anti-growth factor receptor antibody aimed at blocking the
      specific signalling pathways that contribute to hormonal failure. These and other
      approaches provide an opportunity to treat this disease while maintaining an
      acceptable quality of life for patients.

PMID- 8996587
TI  - Prostate cancer treatment strategies based on tumor-specific biological
      principles: future directions.
AB  - Prostate cancer represents a heterogeneous disease entity with varying degrees of
      behavior, aggressiveness, patterns of metastasis, and response to therapy.
      Progressive metastatic prostate cancer is associated with a formidable array of
      morbidity that ultimately contributes to death of the patient. Thus far, there
      has been no convincing evidence to support routine use of non-hormonal
      chemotherapeutic agents or combinations over symptomatic treatment only.
      Furthermore, no single compound or combination has shown a dramatic improvement
      in conventional quality of life parameters over symptomatic treatment only.
      Androgen ablation remains the primary systemic therapeutic modality for this
      disease, yet the intense delineation of mechanisms involved in tumor cell
      metastasis has lead to new therapeutic strategies, ranging from cytotoxic to
      cytostatic, including immunomodulators. Among those strategies currently being
      studied are granulocyte-macrophage colony-stimulating factor-transduced prostate
      cancer vaccines, differentiation therapy, gene therapy, inducers of apoptosis,
      antimetastatic agents, angiogenesis inhibitors, radiation therapy (local and
      systemic), and systemic approaches targeted at prostate cancer morbidity. The
      difficult issue is which agents should be developed and how should we best assess
      the response using standard and newly identified endpoints. Certainly, the future
      of advanced prostate cancer therapy will undergo dramatic changes as a result of
      the continued interaction between the laboratory and the clinic.

PMID- 8996586
TI  - New therapeutic agents for hormone-refractory prostate cancer.
AB  - The identification of active chemotherapeutic agents for use in the treatment of
      advanced hormone-refractory prostate cancer remains a priority of clinical
      research. An estimated 317,100 new cases will be diagnosed in 1996. This
      increased diagnosis of disease can be directly attributed to the widespread use
      of screening serum prostate-specific antigen. However, this has not been
      associated with a reduction in mortality; more than 41,000 men in the United
      States are expected to die of the disease this year. The natural history of
      hormone-resistant disease has remained unaltered, with patients having a median
      survival of only approximately 12 months. Use of surrogate endpoints, such as a
      reduction in prostate-specific antigen or improvement in pain, may be appropriate
      for the evaluation of novel agents or combinations. A number of promising new
      approaches have been recently tested and brought to trial, including combined
      antimicrotubular therapy, camptothecins, and matrix metalloproteinase inhibitors.
      It is only through the development of these and other novel compounds that we can
      hope to affect the natural course of prostate cancer.

PMID- 8996588
TI  - Paclitaxel with carboplatin for the treatment of ovarian cancer.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (135 mg/m2 over
      24 hours) plus cisplatin (75 mg/m2 at a rate of I mg/min) every 3 weeks is widely
      accepted as the new standard of treatment for women with advanced epithelial
      ovarian cancer. A higher dose of paclitaxel over a shorter infusion period is
      under investigation as an alternative because it looks at least as effective and
      is more convenient to administer. However, in combination with cisplatin this
      dose-time schedule causes neurotoxicity in an important number of patients that
      can preclude the delivery of an adequate total dose. One way to decrease the
      incidence of this side effect is to substitute cisplatin with the analogue
      carboplatin. From the present data the conclusion is warranted that it is
      feasible to combine both drugs in an adequate dose and with acceptable toxicity.
      The combination would allow administration to outpatients and may be more
      tolerable, allowing prolonged treatment. The combination also looks attractive
      for re-treatment of women who relapse after completing their first-line
      paclitaxel/cisplatin-based therapy and who have chemotherapy-sensitive disease
      and prognostic features indicating that there is a high likelihood of achieving a
      second durable remission.

PMID- 8996589
TI  - Phase I/II study of paclitaxel, cisplatin, and cyclophosphamide in advanced
      ovarian carcinoma: preliminary results.
AB  - In this phase I/II study, we assessed the impact of paclitaxel (Taxol; Bristol
      Myers Squibb Company, Princeton, NJ) in the treatment of advanced ovarian
      carcinoma combined with the standard regimen cisplatin/cyclophosphamide given as
      follows: paclitaxel 175 mg/m2 (over 3 hours perfusion with standard
      premedication), cisplatin 80 mg/m2 (6 to 12 hours after paclitaxel), and
      cyclophosphamide 400 mg/m2. From February 1994 to January 1996, 27 patients
      (median age, 55 years; age range, 35 to 74 years) were entered into the study.
      Eight patients had distant metastases and 19 had early locoregional disease
      (stage III, 18 patients; stage IC, one patient). Twenty-two patients had
      undergone prior surgery (simple biopsy, six patients; optimally debulked, nine
      patients; suboptimally debulked, seven patients). Twenty-one patients had
      received no prior chemotherapy and six were previously treated with at least one
      platinum-based regimen. A maximum of six courses of
      paclitaxel/cisplatin/cyclophosphamide were given every 21 days. Twenty-three
      patients were evaluable for toxicity: neutropenia (World Health Organization
      grade 3/4), 91% of patients; thrombopenia (World Health Organization grade 3/4),
      13% of patients; two episodes of neutropenia with fever; and neurotoxicity grade
      3, 17% of patients. Alopecia grade 3 was reported in all patients. No
      hypersensitivity reactions and no cardiac toxicity was observed. Among 17
      patients evaluable for response (patients with stage IV disease or stage III
      suboptimally debulked), 12 (70%) clinical complete responses (CRs) and three
      (18%) partial responses were observed. Among the 12 patients with CRs, 10
      underwent second-look laparotomy and seven of them (70%) achieved a pathologic
      CR. In the group of 11 chemotherapy-naive patients evaluable for response, eight
      (72%) achieved a CR and three (28%) achieved a partial response. This combination
      seems to be safe, with very acceptable toxicity, and also seems to be highly
      active in the treatment of patients with advanced ovarian carcinoma.

PMID- 8996590
TI  - Combination paclitaxel and platinum in the treatment of lung cancer: US
      experience.
AB  - Despite marked improvements in the treatment options available for patients with
      lung cancers, more than 85% of patients ultimately relapse and die of their
      disease. Among the most auspicious of new agents available to treat lung cancers,
      paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) also has been the
      most extensively studied. The US experience with this promising new agent is
      reviewed here. It is concluded that paclitaxel, both as a single agent and in
      combination therapies, is as active as other available agents in the treatment of
      stages III and IV small cell and non-small cell lung cancer, whether given as a
      24- or a 1- to 3-hour infusion. In combination therapy, paclitaxel/cisplatin has
      been shown to be superior to etoposide/cisplatin in the treatment of non-small
      cell lung cancer. Further study is needed to clarify the optimal role of
      paclitaxel in combination therapy and to define its optimal dose and schedule in
      therapy for lung cancers.

PMID- 8996591
TI  - Paclitaxel and carboplatin in nonoperable non-small cell lung cancer.
AB  - Based on the high activity of single-agent paclitaxel (Taxol; Bristol-Myers
      Squibb Company, Princeton, NJ) in non-small cell lung cancer (NSCLC) and the
      superior 1-year survival rates of patients with NSCLC treated with carboplatin,
      the Hellenic Cooperative Oncology Group initiated a phase II trial to investigate
      the efficacy and toxicity of the combination of both agents in patients with
      nonoperable stage III and IV NSCLC. Since July 1995, 31 eligible patients have
      entered into this study. All patients received paclitaxel 175 mg/m2 as a 3-hour
      infusion plus carboplatin dosed to an area under the concentration-time curve of
      7, every 3 weeks. No granulocyte colony-stimulating factor was given. Among the
      29 male and two female patients, the median age was 55 years (range, 29 to 73
      years) and the median performance status was I (range, 0 to 2). Most of the
      patients had stage IV adenocarcinoma (19 patients), with poor differentiation (15
      patients). The median number of prior chemotherapy cycles was two, with a range
      of one to six. Among 21 evaluable patients, seven achieved a partial response, 10
      had stable disease, and four had progressive disease. It is too early for
      evaluation in nine patients. Grade 2/3 nonhematologic toxicities included
      alopecia (46.4%), neurotoxicity (3.3%), and myalgia/arthralgia (7.1%). Grade 2/3
      neutropenia was experienced by 10.7% of patients, whereas grade 2
      thrombocytopenia was seen in only 3.3%. One patient died following complications
      of severe allergic reaction. In conclusion, although this study is ongoing, it is
      clear that the combination of paclitaxel and carboplatin is effective and well
      tolerated in patients with nonoperable NSCLC.

PMID- 8996593
TI  - Combinations of paclitaxel and etoposide in the treatment of lung cancer.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and etoposide are
      two chemotherapy agents with broad cytotoxic activity but different mechanisms of
      action and resistance. Previous in vitro studies of their combined cytotoxicity
      have yielded conflicting results. We evaluated the effects of drug scheduling in
      cell growth inhibition in lung and breast human cancer cell lines. A clonogenic
      assay with either simultaneous or sequential 24-hour incubation of paclitaxel and
      etoposide was used to assess growth inhibition, and the combination index was
      used to evaluate drug interactions. In these studies, including the A549 human
      lung cancer cell line, mild antagonism (combination index, > 1) was observed with
      concurrent exposure of paclitaxel and etoposide, but synergism (combination
      index, < 1) was observed when the drugs were incubated sequentially. In view of
      the wide range of antitumor activity of both paclitaxel and etoposide, and the
      potential importance and clinical impact of optimizing drug doses and schedules,
      we recently completed a phase I study with the following objectives: (1) to
      determine the maximum tolerated dose of paclitaxel given intravenously on day 10
      after 10 days of oral etoposide and (2) to investigate the toxicity profile of
      this combination of agents. Three consecutive cohorts consisting of a total of 29
      patients with various measurable or assessable tumors were treated with
      paclitaxel by intravenous infusion over 3 hours after receiving 10 days of
      etoposide 50 mg orally twice daily. Conclusions for this clinical study were that
      the combination was feasible and tolerable and had demonstrated antitumor
      activity in a group of mostly pretreated patients. The recommended doses for
      phase II studies were etoposide 50 mg twice daily for 10 days followed by
      paclitaxel 150 mg/m2 intravenously over 3 hours. A phase II study in patients
      with extensive small cell lung cancer, with appropriate translational studies,
      has been initiated.

PMID- 8996592
TI  - Paclitaxel via 1-hour infusion: rationale and pharmacology.
AB  - Although the initial choice to evaluate a 3-hour infusion of paclitaxel (Taxol;
      Bristol-Myers Squibb Company, Princeton, NJ) was arbitrary, the attenuated
      schedule has since proven safe and active against several neoplasms. Shorter
      infusions are easier to administer, particularly in combination chemotherapy and
      combined-modality therapy, prompting our investigations of 1-hour paclitaxel
      infusions in more than 500 patients and approximately 2,000 treatment courses.
      The toxicity, activity, and pharmacology of 1- and 3-hour infusions of paclitaxel
      appear to be similar. Results of phase II trials document that 1-hour paclitaxel
      infusions can be administered safely, and notable activity has been seen against
      several neoplasms, including cancers of the lung, breast, and urothelium, as well
      as advanced squamous carcinomas and tumors of unknown origin. This report also
      describes some limited pharmacologic data of 1-hour paclitaxel compared with
      longer infusions.

PMID- 8996594
TI  - Simultaneous radiochemotherapy with paclitaxel in non-small cell lung cancer: a
      clinical phase I study.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the
      most active single agents available for the treatment of non-small cell lung
      cancer (NSCLC), with reported response rates of 21% to 24%. Its observed
      radiosensitizing effect is attributed to its interruption of cell development at
      the G2/M phase of the cell cycle, when cells are most sensitive to the killing
      effects of ionizing radiation. This phase I study of paclitaxel and simultaneous
      radiation therapy in patients with previously untreated, locally advanced
      inoperable stage IIIA/B NSCLC was designed to determine the maximum tolerated
      paclitaxel dose, to define the safety and toxicity of this combined modality, and
      to obtain preliminary data on its activity. Patients received a fixed dose of
      radiotherapy (1.8 Gy/d, 5 days a week, in shrinking-field technique, for a total
      dose of 59.4 Gy) and concomitant chemotherapy with a 3-hour infusion of
      paclitaxel once weekly on day 1, initially at a dose of 45 mg/m2, for 3 weeks.
      This dose remained constant during study levels 1 to 3, with the number of weeks
      of treatment increasing to 5 and 7 at levels 2 and 3, respectively. At dose level
      4, the paclitaxel dose was increased to 55 mg/m2 over 7 weeks. Of 22 NSCLC
      patients who entered the study, 18 are evaluable for toxicity and response.
      Responses included one complete and 10 partial remissions; the other seven
      patients had minimal improvement. The therapy was well tolerated; no severe
      adverse events were associated with paclitaxel or radiotherapy. This combined
      modality appears to be a practicable and effective treatment for NSCLC. The
      maximum tolerated paclitaxel dose has not yet been reached, and dose escalation
      is planned.

PMID- 8996595
TI  - Paclitaxel and radiotherapy in the treatment of advanced non-small cell lung
      cancer.
AB  - Sixteen patients affected by previously untreated non-small cell lung cancer
      stage IIIB or IV received radiotherapy and paclitaxel (Taxol; Bristol-Myers
      Squibb Company, Princeton, NJ) as radiation sensitizer in an open, nonrandomized
      pilot study to find the maximum tolerated dose of the drug concomitantly combined
      with radiation. Paclitaxel was given as a 3-hour infusion once weekly at a dose
      escalating by 10 mg/m2/wk for every patient cohort, starting at 40 mg/m2/wk and
      continuing to 80 mg/m2/wk. Conventionally fractionated (2 Gy/d for 5 d/wk for 5
      weeks) radiotherapy up to 50 Gy was delivered to the primary tumor and
      mediastinum with a 6-mv linear accelerator. Hematologic toxicity has been very
      low; grade 3 World Health Organization nonhematalogic toxicities have been
      registered only at the 80 mg/m2/wk dose level. Seven patients achieved a major
      response, three patients had stable disease, and five patients progressed; three
      patients are still responding, whereas the others are relapsed and five of them
      died of disease. The median duration of response was 5 months. Paclitaxel may be
      safely combined with radiation at the maximum tolerated dose of 70 mg/m2/wk. Our
      data seem to confirm the radiosensitizing effect of the drug, independent of the
      dose level. Low doses of paclitaxel given as a single agent are unable to control
      metastatic disease.

PMID- 8996596
TI  - Paclitaxel and doxorubicin in metastatic breast cancer.
AB  - For the past decades the anthracyclines have been regarded as among the most
      active drugs for the treatment of metastatic breast cancer. However, the 5-year
      survival rate in patients with stage IV breast cancer continues to be below 20%,
      and new active drugs and drug combinations clearly must be explored. Paclitaxel
      (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been demonstrated to be
      highly effective in treating patients with advanced breast cancer, including
      those with anthracycline-resistant breast cancer, a fact that has led to efforts
      to combine paclitaxel and anthracyclines. Several studies aiming to define the
      optimal dose and schedule of combination paclitaxel/doxorubicin have now been
      completed or are ongoing. Phase I/II studies have yielded encouraging preliminary
      response rates but quite variable toxicity profiles depending on the schedule
      used. These clinical trials involving combination paclitaxel/doxorubicin are
      reviewed, with special emphasis on the short-infusion trials.

PMID- 8996597
TI  - Paclitaxel combinations as front-line and salvage chemotherapy regimens in
      advanced breast cancer.
AB  - Thirty-two patients with advanced breast cancer have been treated with epirubicin
      90 mg/m2, immediately followed by paclitaxel (Taxol; Bristol-Myers Squibb
      Company, Princeton, NJ) infused over 3 hours, every 21 days. The starting
      paclitaxel dose was 135 mg/m2, increased in subsequent triplets of patients until
      the maximum tolerated dose was reached at 200 mg/m2. One hundred seventy-six
      courses have been administered; dose-related grade 4 neutropenia was observed in
      66% of the courses, with 12 episodes of febrile neutropenia. Two patients showed
      a decline of left ventricular ejection fraction below 50% after six courses, but
      no signs of congestive heart failure have been reported. The response rate is 76%
      (95% confidence interval, 56% to 90%), with 14% complete remissions. This level
      of activity is encouraging considering that 84% of the patients had failed
      adjuvant chemotherapy (with anthracyclines in 14 cases), and 19 had progressive
      disease following hormone therapy for metastasis. In another study, the toxicity
      and activity of a salvage regimen consisting of paclitaxel 135 mg/m2 over 3 hours
      plus vinorelbine 25 mg/m2 in an intravenous bolus on day 1 were evaluated;
      vinorelbine was given again on day 8 (in 14 patients) or on day 3 (in 20
      patients), and the courses were repeated every 3 weeks. Thirty-four previously
      treated patients with advanced breast cancer entered the study; 20 had received
      one prior line of chemotherapy, II had two lines, and three patients had three
      lines. Thirty-two patients had been exposed to anthracyclines. Grade 4
      neutropenia was observed in 64% of the courses, with 13 episodes of febrile
      neutropenia; four episodes of grade 3 mucositis have been reported with
      vinorelbine days 1 and 3. A delay in the administration of chemotherapy was
      necessary in 17% of the courses with vinorelbine days 1 and 8 and 16% of the
      courses with vinorelbine days 1 and 3; moreover, the vinorelbine dose was reduced
      or the drug omitted on day 8 in 86% of the courses and on day 3 in 16% of the
      course. An objective response was achieved in 43% of the patients. In conclusion,
      the combination of paclitaxel plus vinorelbine is an active salvage regimen and
      can be administered at greater dose intensity with the day 1 and 3 schedule.

PMID- 8996598
TI  - Paclitaxel-containing high-dose chemotherapy: the University of Colorado
      experience.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the
      most important antineo-plastic agents developed over the last 20 years. It has
      proven activity in breast cancer, ovarian cancer, and non-small cell lung cancer.
      In this study, the possibility of incorporating paclitaxel into a high-dose
      chemotherapy regimen targeting patients with breast cancer was evaluated. From a
      widely used regimen composed of cyclophosphamide, cisplatin, and carmustine,
      carmustine was deleted and paclitaxel added at the beginning of the regimen. The
      dose of paclitaxel was then escalated until life-threatening toxicities occurred.
      It was demonstrated that the dose of paclitaxel could be escalated to 775 mg/m2,
      combined with cyclophosphamide 5,625 mg/m2 and cisplatin 165 mg/m2, followed by
      autologous hematopoietic progenitor cell support. A phase II study testing this
      combination in patients with chemotherapy-responsive metastatic breast cancer has
      been initiated. A new phase I study to test the feasibility of adding carmustine
      to this paclitaxel-based regimen is currently under way. The status of this study
      is briefly summarized.

PMID- 8996599
TI  - Clinical development of topoisomerase-interactive drugs.

PMID- 8996600
TI  - Topoisomerases in human leukemia.

PMID- 8996602
TI  - Mechanisms of topoisomerase I inhibition by anticancer drugs.

PMID- 8996601
TI  - Preclinical and clinical development of camptothecins.

PMID- 8996603
TI  - Drug resistance mechanisms of topoisomerase I drugs.

PMID- 8996604
TI  - Mechanism of action of topoisomerase II-targeted antineoplastic drugs.

PMID- 8996605
TI  - Determinants of cellular sensitivity to topoisomerase-targeting antitumor drugs.
AB  - It is now clear that topoisomerase activity level is an important determinant of
      sensitivity to topo drugs. The regulation of topoisomerases is no doubt complex
      and multifaceted and is probably accomplished through redundancy at many control
      levels. The mechanism(s) of altered topo I expression in certain tumor types is
      unknown, but may be related to the central importance of topoisomerases in
      proliferating cell functions (transcription, replication, etc.), and the aberrant
      and chronic activation of these functions as a result of specific tumorigenic
      alterations. Small differences in sensitivity to chemotherapy can have a dramatic
      effect on cure rates, and therefore subtle cell type-specific differences may be
      important determinants of drug sensitivity. Whether abnormal topoisomerase
      quantity and specific activity are associated with resistance or sensitivity to
      topoisomerase-targeted chemotherapy in the clinic is now being studied.
      Determinants downstream of cleavable complex formation that affect the
      sensitivity of tumor versus normal cells to topo drugs in particular and DNA
      damaging agents in general are little known. The goal of enhancing selective
      tumor cell killing relative to the normal cells that are dose limiting may be
      achieved either by overcoming tumor cell resistance or by protecting normal
      cells. Both of these strategies will become more feasible as specific molecular
      differences between tumor and normal cells are being rapidly identified and new
      combination therapies that take advantage of these differences are being designed
      and tested.

PMID- 8996606
TI  - Resistance of mammalian tumor cells to inhibitors of DNA topoisomerase II.

PMID- 8996607
TI  - A bacteriophage model system for studying topoisomerase inhibitors.
AB  - The bacteriophage T4 provides a unique and informative system in which to study
      the mechanism of action of antitumor agents that inhibit type II DNA
      topoisomerases. The evolutionary conservation of inhibitor sensitivity provides a
      strong argument for a conserved inhibitor binding site at or very near the active
      site of the enzyme-DNA complex. Studies of the wild-type and drug-resistant T4
      topoisomerases have provided several important arguments that the drug binding
      site is located very near the phosphodiester bonds that are cleaved by the
      topoisomerase. One reasonable model is that the inhibitors intercalate between
      the two bases on each side of the cleaved phosphodiester bond and physically
      block the resealing reaction. Finally, genetic analyses using the T4 system have
      provided some of the most detailed information concerning the role of type II
      topoisomerase in various aspects of DNA metabolism. The topoisomerase is involved
      in two distinct pathways of mutagenesis, one that generates frameshift mutations
      and the other involving gross DNA rearrangements. Both pathways operate precisely
      at the DNA sites that are cleaved by the enzyme in the presence of inhibitors.
      Furthermore, recombinational repair can apparently correct lesions that are
      generated upon inhibition of the T4 topoisomerase, and these inhibitors
      correspondingly stimulate homologous recombination in phage-infected cells. A
      complete description of the action of antitumor agents that inhibit type II
      topoisomerases clearly involves many diverse aspects of nucleic acid metabolism.

PMID- 8996608
TI  - Drugs affecting trypanosome topoisomerases.

PMID- 8996609
TI  - Yeast as a genetic model system for studying topoisomerase inhibitors.

PMID- 8996610
TI  - DNA topoisomerase inhibitors as antifungal agents.

PMID- 8996612
TI  - Appendix. I: An introduction to DNA supercoiling and DNA topoisomerase-catalyzed
      linking number changes of supercoiled DNA.

PMID- 8996611
TI  - Design of topoisomerase inhibitors to overcome MDR1-mediated drug resistance.
AB  - Human colon tumor xenografts are known to be refractory to most chemotherapeutic
      anticancer drugs. Recent studies have demonstrated that a class of topoisomerase
      I inhibitors, camptothecins, exhibits unprecedented antitumor activity against
      human colon tumor xenografts in nude mice (Giovanella et al., 1989; Potmesil et
      al., 1991). The ability of camptothecin to overcome MDR1-mediated resistance may
      be one important contributing factor to camptothecin's impressive activity (Chen
      et al., 1991). If this interpretation is correct, it will be promising to develop
      new drugs that can overcome MDR1-mediated resistance for treating certain human
      solid tumors. Admittedly, MDR1-mediated resistance is only one of the many
      mechanisms of drug resistance in tumor cells. Designing new drugs for various
      resistance tumors will require fundamental information on various drug resistance
      mechanisms. It will eventually be possible to tailor drugs for particular drug
      resistant tumors. Using topoisomerase inhibitors, we have begun to understand
      some of the parameters that may have to be considered for rational drug design.

PMID- 8996613
TI  - Appendix. II: Alignment of primary sequences of DNA topoisomerases.

PMID- 8996614
TI  - A lesson in history and medicine.

PMID- 8996615
TI  - African-Americans on maintenance dialysis: a review of racial differences in
      incidence, treatment, and survival.
AB  - African-Americans are the fasting growing racial minority with end stage renal
      disease (ESRD) in the United States. Currently, African-Americans comprise
      approximately 31% of the ESRD population. African-Americans are almost a decade
      younger than their white (referring to non-Hispanic white) counterparts with ESRD
      with a mean age of 58 years old. Although African-Americans systematically
      receive less dialysis than whites (Kt/V of 1.05 versus 1.18, respectively), their
      survival is higher. The 2-year survival probability of African-Americans is 66.2%
      in comparison with 59.8% for whites. This improved survival with ESRD is
      accompanied by an improved quality of life for African-Americans. Their enhanced
      quality of life is reflected by a greatly decreased frequency of withdrawing from
      dialysis treatments. In this article, we will examine the reasons why African
      Americans have an excessive incidence of selective diseases that culminate in
      ESRD. We will explore the factors that influence the difference in dialysis
      modality selection between African-Americans and whites. Lastly, we will pose and
      judge several hypotheses that may account for the improved survival enjoyed by
      African-Americans with ESRD. We contend that research to clarify the basis for
      these differences between African-Americans and whites with ESRD will improve
      outcomes for both populations and is fiscally sound health policy.

PMID- 8996616
TI  - Family support and survival among African-American end-stage renal disease
      patients.
AB  - Family support is a critical factor in the survival of African-American end-stage
      renal disease (ESRD) patients. Research suggests that survival among ESRD
      patients is related to the quality of family support. There is empirical evidence
      for low family support as a risk factor for early mortality among African
      American ESRD patients. This review describes findings from studies linking
      family support and patient survival in African-American ESRD patients. It also
      discusses findings that suggest treatment adherence as a mediator between family
      support and patient survival. Finally, the implications for clinical practice and
      future research with African-American ESRD patients are discussed.

PMID- 8996618
TI  - Adaptation of African-American cultural and food preferences in end-stage renal
      disease diets.
AB  - Emphasis on culturally based and ethnically oriented food selection by nutrition
      health professionals is needed to effectively plan therapeutic diets. With the
      influx of numerous ethnic groups into the United States and the merging of
      cultural practices, it is important for dietitians to become familiar with
      specific ethnic foods and regional cooking techniques. In this review, the
      influence of immigration on regional cuisine is documented. Dominant patterns of
      typical African-American ethnic menus for holidays and special celebrations are
      revealed. Analysis of common foods in the African-American culture are listed for
      reference, along with a glossary of ethnic foods. Renal guidelines are presented
      for various stages of end-stage renal disease. When planning a specific renal
      diet, African-American ethnic preferences can be incorporated into the meal plan
      or appropriate substitutions can be recommended. A suggested sample menu for
      hemodialysis patients that incorporates African-American preferences is included
      for reference. Health risks also influence current eating trends of the African
      American population. Hypertension and obesity are two physiological factors that
      need to be evaluated and considered when planning renal diets. Literacy skills
      and appropriate dietary instructional material is discussed. Reference materials
      developed for nutrition professionals are important and can be used in the
      planning of renal diets for African-Americans.

PMID- 8996617
TI  - Withdrawal from dialysis: a review with an emphasis on the black experience.
AB  - Withdrawal from dialysis has been shown to be a common occurrence in treated end
      stage renal disease. Interestingly, there have been several reports documenting
      that blacks withdraw from dialysis one half to one third the rate of whites.
      There has been little research into the reasons for this marked discrepancy. This
      article reviews the existing literature on the different rates of withdrawal in
      blacks compared with whites. It then draws on a broad range of literature,
      including sociology, psychiatry, and anthropology, to propose possible reasons
      for the differences. From this review, it would seem that both medical and
      cultural factors play important roles in the decisions about withdrawal, but that
      cultural beliefs and attitudes are more important. More research is needed in
      both the medical and cultural aspects of rates of withdrawal to help explain the
      observed differences in blacks compared with whites.

PMID- 8996619
TI  - Poorer graft survival in African-American transplant recipients cannot be
      explained by HLA mismatching.
AB  - African-American kidney-transplant recipients have exhibited a higher rate of
      graft failure than whites and other patient groups. Many have attributed this
      discrepancy to disparities in HLA matching against a predominantly white donor
      pool. We compared the relative risks of cadaveric and living-related graft
      failure in African-American, white, Hispanic, and Asian transplant recipients,
      adjusting for a variety of demographic and clinical covariates. The relative
      risks of graft failure were increased by 44% and 73% in African-American
      recipients of cadaveric and living-related organs, respectively. Although Asians
      were subject to a comparable degree of HLA mismatching, cadaveric graft survival
      in Asian recipients was superior to that in whites. These results suggest that
      other variables not captured by registry data account for the increase in graft
      failure observed in African-Americans. More focused investigation into the causes
      and prevention of graft failure in African-Americans is required.

PMID- 8996620
TI  - Postrenal transplant compliance from the perspective of African-Americans,
      Hispanic-Americans, and Anglo-Americans.
AB  - Medication compliance by patients is a subject that has attracted attention
      because it has been identified as the third leading cause of renal graft loss.
      The purpose of this study was to gather specific information about renal
      transplant recipients' cognitions, emotions, and behaviors during the postrenal
      transplant compliance process. Data from 519 renal transplant patients were
      collected through mailed surveys; chart audits were conducted for 397 patients in
      the sample. Findings revealed that 96 (18%) of the transplant recipients had been
      noncompliant with immunosuppressive medications. Factors related to noncompliance
      included being away from home, length of time since transplant, age, gender, and
      ethnicity, as well as patients' beliefs regarding how long posttransplant
      symptoms would persist and their beliefs about the effectiveness of
      immunosuppressive medications. Of particular interest were the findings related
      to compliance by African-American patients, which challenge conventional
      thinking. Implications for assessing patient compliance, patient education, and
      further research are discussed.

PMID- 8996621
TI  - Disordered sleep and noncompliance in a patient with end-stage renal disease.
AB  - Sleep disorders are relatively common in patients with end-stage renal disease,
      but the diagnosis may be difficult to establish because of the similarity of
      uremic symptoms to those of the sleep apnea syndrome. After excluding anatomic
      and metabolic disorders associated with excessive sleepiness and disordered
      breathing in sleep and after ensuring that the patient is receiving adequate
      dialysis, the sleep disorder should be diagnosed using polysomnography.
      Continuous positive pressure airway breathing is an effective treatment for
      hemodialysis patients with obstructive sleep apnea syndrome, but the use of this
      machinery requires patient compliance, as does the delivery of an adequate amount
      of dialysis. The difficulties adjusting to end-stage renal disease requiring
      dialysis can be multiplied by the coexistence of a sleep disorder that requires
      some ventilatory assistance at night; the case presented in this article
      characterizes precisely that circumstance.

PMID- 8996622
TI  - Transport characteristics of the slow therapies: implications for achieving
      adequacy of dialysis in acute renal failure.
AB  - Slow continuous renal replacement therapy is used primarily to treat critically
      ill patients with acute renal failure. Knowledge of the small solute transport
      characteristics in continuous renal replacement therapy (CRRT) provides a
      rational basis for the manipulation of operating conditions to achieve desired
      clearances and, hence, desired metabolic control. These manipulations simply
      involve varying the dialysate inflow rate, the ultrafiltration rate, and the
      substitution fluid replacement rate. For the diffusion-based therapies, the
      condition of dialysate saturation, ie, exiting dialysis fluid urea nitrogen (FUN)
      approximating inflowing plasma water urea nitrogen (BUN, ie, the FUN/BUN ratio
      approximately 1), simplifies these manipulations. Examples of the calculations
      required to compute urea generation rate, protein catabolic rate, and the desired
      clearances are given. However, all of these calculations leave unanswered the
      question of "what is adequate dialysis" in the critically ill patient with acute
      renal failure. In the absence of the data that are required to answer this
      question, one can only say that if dialysis makes a difference, the persistently
      high mortality rate in intensive care unit acute renal failure suggests that
      patients are not receiving enough Kt/V. The reasons why CRRT is inherently more
      efficient than intermittant hemodialysis are explored. The usual reasons why
      prescribed therapy is less than delivered therapy with respect to slow continuous
      therapy are also discussed.

PMID- 8996623
TI  - Making decisions about end-stage renal disease treatment: a review of theories
      and issues.
AB  - Multiple theories and models of decision-making have been reported in the popular
      and scientific literature. Decisions and choices about health care are some of
      the most dramatic and difficult that humans make. The interactive role of patient
      and health care professional in circumstances of urgency, stress, and possible
      unpredictability is complex. This article reviews some of the theories of
      decision-making and their implementation or usefulness in the end-stage renal
      disease setting. In caring for patients, health professionals need to identify
      their approach to the decision-making process with special concern for the
      patient role in this process.

PMID- 8996624
TI  - Tracking multidisciplinary outcomes in the dialysis patient population.

PMID- 8996626
TI  - Effects of deferoxamine on H2O2-induced oxidative stress in isolated rat heart.
AB  - During myocardial reperfusion injury, iron has been implicated in the Fenton
      based generation of hydroxyl radical, .OH, leading to further organ injury.
      Although previous studies have investigated the protective effect of iron
      chelators including deferoxamine (DFX) in myocardial reperfusion injury, there is
      little information regarding the role of iron chelation during oxidative stress
      produced by H2O2 on the heart. Isolated hearts from male Sprague-Dawley rats were
      retrograde-perfused with Krebs-Henseleit solution at 5 ml/min. After a 60-min
      equilibration, oxyradical challenge was instituted by the addition of H2O2 (200
      600 microM) to the perfusate for 60 min. A subgroup of animals received DFX (400
      microM) in the perfusate prior to challenge with 400 microM H2O2. Contractility
      was continuously monitored; perfusate samples for glutathione (GSH) and lactate
      dehydrogenase (LDH) estimations were collected at 30-min intervals. Headspace
      ethane, an indicator of lipid peroxidation, was estimated at 30-min intervals by
      gas chromatography. Control hearts maintained contractility during the perfusion
      period. H2O2 perfusion caused a dose dependent decrease in myocardial
      contractility; DFX pretreatment was partially protective. Headspace ethane slowly
      accumulated in control hearts; perfusion with H2O2 caused dose dependent increase
      in ethane accumulation indicative of enhanced lipid peroxidation. GSH and LDH in
      the perfusate remained low in control hearts. In contrast, H2O2 treated hearts
      had a dose dependent increase in the efflux of GSH and LDH which was markedly
      increased by perfusion with 600 microM H2O2. Pretreatment with DFX did not
      significantly reduce GSH or LDH efflux from hearts perfused with peroxide. While
      H2O2 perfusion causes a dose dependent decrease in myocardial contractility with
      a corresponding increase in headspace ethane release with GSH & LDH efflux
      indicative of oxidative stress, concurrent treatment with DFX reduces myocardial
      dysfunction and ethane generation. However, sublethal damage of plasma membrane
      still continues as reflected by continuous enhancement of LDH efflux, possibly
      indicating involvement of other reactive species besides hydroxyl radical.

PMID- 8996625
TI  - Proliferative response of human and minipig smooth muscle cells after coronary
      angioplasty to growth factors and platelets.
AB  - OBJECTIVES: Platelets aggregating at the site of angioplasty, shown to be a
      potent proliferative stimulus for cultured smooth muscle cells (SMC), could
      contribute to proliferation after angioplasty. METHODS: SMC were cultivated from
      human aorta and restenosed coronary lesions as well as from minipig aorta and
      from normal and post angioplasty coronary artery segments (n = 6 per source). 3H
      thymidine incorporation was used as a measure of proliferation. RESULTS: 3H
      thymidine incorporation varied greatly after passage 7 in all cell lines, but was
      significantly higher in SMC from human coronary restenosed lesions compared to
      those from human aorta and minipig coronary post angioplasty segments in passage
      2 (44 +/- 6.4 x 10(3) cpm/5000 SMC vs 20 +/- 3.9 and 12.1 +/- 2.1). However, all
      SMC exhibited a dramatic increase of 3H-incorporation after passage 7. Growth
      factors stimulated 3H-thymidine incorporation either dose dependently (PDGF-BB
      and bFGF) or only very modestly (PDGF-AA, EGF, IGF-1). The most potent
      stimulation was seen with PDGF-BB, 50 ng/ml, and was 17 +/- 6% (human restenosed)
      and 16 +/- 8% (minipig post angioplasty) of the values observed after stimulation
      with 10% fetal calf serum. The most effective combination of growth factors, PDGF
      BB (50 ng/ml) + bFGF(20 ng/ml) + IGF-1 (50 ng/ml), produced a 3H-thymidine
      incorporation of 44 +/- 10% (human restenosed) and 42 +/- 11% (minipig post
      angioplasty) of FCS values. Stimulation by isolated platelets was dose dependent
      and significantly higher: 75 +/- 19% and 70 +/- 15% of FCS values for those SMC.
      CONCLUSIONS: 1) SMC from all sources studied exhibit significant changes of
      proliferation with increasing passages, excluding the comparability of data
      obtained with cells in different passages. 2) Data obtained with SMC from any
      source might not apply for SMC from human coronary restenosed lesions. 3)
      Currently tested growth factors do not fully account for the proliferative effect
      of platelets on cultured SMC.

PMID- 8996627
TI  - Suppression of the degradation of adenine nucleotides during ischemia may not be
      a sufficient mechanism for infarct size limitation by preconditioning.
AB  - Preconditioning is known to decelerate degradation of the tissue adenine
      nucleotides during ischemia and to delay ischemic myocardial necrosis. However,
      it is not known whether these two phenomena are related. To obtain an insight
      into this question, the present study examined whether adenosine and B2 receptor
      antagonists, which block the infarct size-limiting effect of preconditioning,
      modify the interstitial purine levels during preconditioning and subsequent
      sustained ischemia. In pentobarbital anesthetized open-chest rabbits, a
      microdialysis probe was placed in the territory of a branch of the left coronary
      artery, and perfused with Ringer solution. Preconditioning was performed with 5
      min ischemia/5 min reperfusion. Dialysate adenosine and inosine were elevated
      from the baseline values of 0.064 +/- 0.011 and 0.329 +/- 0.044 microM to 0.189
      +/- 0.069 and 4.106 +/- 1.451 microM, respectively during preconditioning, but
      their elevation during a subsequent 20 min of ischemia was significantly lower
      compared with that in the non-preconditioned myocardium. This suppression of the
      purine accumulation during ischemia by preconditioning was not abolished by 2
      micrograms/kg of Hoe 140, a specific B2 receptor antagonist, or by 10 mg/kg of 8
      phenyltheophylline, a non-selective adenosine receptor antagonist. Since the
      doses of Hoe 140 and 8-phenyltheophylline are sufficient to block the infarct
      size-limiting effect of preconditioning, the present results suggest that there
      is a dissociation between the suppression of adenine nucleotide degradation
      during ischemia by preconditioning and the enhancement of myocardial resistance
      against infarction. Thus, it is unlikely that a reduction of adenine nucleotide
      utilization by preconditioning is sufficient to protect the myocardium against
      ischemic necrosis.

PMID- 8996629
TI  - Ischaemic preconditioning protects against myocardial dysfunction caused by
      ischaemia in isolated hypertrophied rat hearts.
AB  - Although ischaemic preconditioning (PC) has been shown to protect normal hearts
      from a subsequent ischaemic insult, its protective effect on the hypertrophied
      myocardium has not been widely studied. This study was designed to investigate
      whether ischaemic preconditioning protects hearts with hypertrophy (HYP). Cardiac
      HYP was produced in rats by suprarenal abdominal aortic constriction of 5 weeks'
      duration, and was defined as left ventricular weight: body weight [LVW: BW
      (mg/g)] ratio over 3.0. Isolated rat hearts were perfused with a modified Krebs
      Henseleit buffer at 37 degrees C in a Langendorff preparation. Hearts from sham
      operated animals (NORM) and those with HYP underwent a PC protocol consisting of
      3 min of global zero flow ischaemia, 5 min of reperfusion followed by 5 min of
      ischaemia and 5 min of reperfusion. This was followed by 20 min ischaemia and 45
      min reperfusion. Control hearts in the HYP and NORM groups were not subjected to
      the PC protocol. There were, thus, four experimental groups: NORM control (n =
      9), NORM, PC (n = 9), HYP control (n = 9), HYP, PC (n = 11). The recovery of
      function after ischaemia was evaluated by recovery of left ventricular developed
      pressure (LVDP) expressed as % of the initial value (LVDP%). The LVW: BW ratio
      for the HYP groups was 3.4 (SEM 0.08). LVDP% was higher (p < 0.01) in
      preconditioned groups as compared with controls. In NORM control recovery was
      49.3 (6.1), NORM, PC 76.5 (3.4), HYP control 39.8 (4.6) HYP, PC 70.1 (4.1). These
      data indicate that the ability of preconditioning to protect against ischaemic
      ventricular dysfunction is preserved in this model of cardiac hypertrophy.

PMID- 8996628
TI  - Cardioprotection associated with preconditioning in the anesthetized ferret.
AB  - The cardioprotective effect of ischemic preconditioning (PC) was investigated in
      the anesthetized ferret model of myocardial ischemia followed by reperfusion. PC
      of 2, 5, or 10-min duration, followed by 10-min reflow, was studied in animals
      subjected to 60-min sustained LAD coronary artery ischemia followed by 5-h
      reperfusion. Infarct size was determined by tetrazolium staining. Sham PC ferrets
      had a mean infarct of 72% of risk zone. A 2-min or 5-min cycle of PC
      significantly reduced tissue damage to 54% (p < 0.05) and 44% (p < 0.01),
      respectively. Infarct reduction associated with 10-min ischemic PC was not
      significant (57% of AAR). The cardioprotective effects of 5-min PC were lost when
      sustained ischemia was prolonged to 75 or 90-min. Myocardial salvage afforded by
      5-min PC was also abolished by both a) inhibition of ATP-sensitive potassium
      channels using either glyburide or 5-HD and b) blockade of adenosine receptors
      with the A1 selective agent DPCPX. In the absence of PC, activation of ATP
      sensitive potassium channels with the cardiac-selective agonist BMS-180448
      significantly (p < 0.01) reduced infarct size from 66% to 37% of the risk zone.
      Cardioprotection, or its loss, was not the result of hemodynamic alterations
      occurring during PC, drug administration, or the coronary occlusion and
      reperfusion phases. Based upon its body size and lack of extensive myocardial
      collateral circulation the ferret offers a usefull alternative small species for
      study of ischemia and reperfusion salvage. It is concluded in the ferret that: a)
      the threshold for PC is less than in either the rat, rabbit, or dog; unlike the
      dog and pig, the beneficial effects of PC are b) reduced when the ischemic PC
      interval is extended to 10-min or c) lost if sustained coronary occlusion is
      maintained for a period of 75-min or longer; and last, a role in PC for both d)
      ATP-sensitive potassium channels and e) adenosine A1 receptors can be
      demonstrated.

PMID- 8996630
TI  - Cell-type specificity of preconditioning in an in vitro model.
AB  - We investigated whether preconditioning could protect several cultured cell
      lines, to determine whether the protection is specific for cells derived from
      different myogenic and non-myogenic sources. Ischemia was simulated by
      centrifugation of cells into a pellet, and cell viability was determined by
      hypotonic trypan blue solution. Preconditioning was produced by brief exposures
      to either glucose-free solution or metabolic inhibition. Freshly isolated rabbit
      ventricular myocytes were studied to confirm that preconditioning occurs in this
      model. We then compared these results to those in several cultured cell lines,
      including HEK 293 cells derived from human embryonic kidney, HIT-T15 cells from
      Syrian hamster pancreatic islets, and C2C12 cells from mouse skeletal muscle. In
      the latter cell line, we also determined whether differentiation alters
      preconditioning. Preconditioning protected rabbit ventricular myocytes: the
      percentage of dead cells was decreased from 36.8 +/- 4.7% in the control group to
      23.0 +/- 5.2% in the preconditioned group after 60 min and from 50.7 +/- 2.1% in
      the control group to 25.5 +/- 4.5% in the preconditioned group after 120 min
      ischemia (p < 0.02). In contrast, there was no protection from preconditioning in
      HEK 293 cells or HIT-T15 cells. Preconditioning did not protect C2C12 myoblasts
      either. Interestingly, after C2C12 myoblasts had differentiated into myotubes
      (induced by exposing the cells to low-serum medium), they could then be protected
      by preconditioning (46.3 +/- 3.6% in the control group vs 26.0 +/- 2.7% in the
      preconditioned group after 60 min and 67.4 +/- 3.6% in the control group vs 46.0
      +/- 4.6% in the preconditioned group after 120 min ischemia; p < 0.05). In
      conclusion, protection from preconditioning is cell-type specific. The presence
      of endogenous KATP channels (which are plentiful in HIT-T15 cells) is
      insufficient to enable preconditioning of the cell. Among the various cell types
      studied, only differentiated muscle cells (rabbit ventricular myocytes and C2C12
      myotubes) exhibited preconditioning.

PMID- 8996631
TI  - Mast cell degranulation does not contribute to ischemic preconditioning in
      isolated rabbit hearts.
AB  - Preconditioning the heart with a short period of ischemia makes it resistant to
      infarction from a subsequent ischemic insult. We have proposed that
      preconditioning is triggered by the release of endogenous substances including
      adenosine which activate protein kinase C through receptormediated cell signaling
      pathways. However, it has also been proposed that the initial brief ischemia may
      result in mast cell degranulation without significant myocardial damage, making
      it less likely that the toxic granule contents could be released to irreversibly
      damage vulnerable myocardial cells during the subsequent prolonged ischemia. To
      study the role of mast cells in ischemic preconditioning (PC) isolated rabbit
      hearts were subjected to 30 min of regional ischemia followed by 120 min of
      reperfusion. Infarct size was measured with triphenyltetrazolium chloride. In
      control hearts infarction was 31.9 +/- 2.6% of the risk zone. Preconditioning
      with 5 min of global ischemia and 10 min of reperfusion reduced infarct size to
      5.6 +/- 6.1% (p < 0.01). When disodium cromoglycate (DSCG)(10 microM), a mast
      cell stabilizer, was infused shortly before the long ischemia it did protect the
      heart (12.8 +/- 2.9% infarction, p < 0.01 vs control) which supports the mast
      cell theory. However, a mast cell degranulating agent, compound 48/80 (24 mg/L),
      added to the perfusate prior to the 30 min ischemic period could not mimic PC
      (39.7 +/- 5.6% infarction). Mast cell granules are rich in histamine, and the
      latter was assayed in myocardium by immunoassay as a marker of intact granules.
      In homogenized left ventricle from normal rabbit hearts and those following a
      standard PC protocol of 5-min global ischemia/10-min reperfusion, histamine
      contents were 9.3 +/- 1.4 and 8.9 +/- 1.4 ng/g wet tissue, respectively. Compound
      48/80 reduced histamine levels to 2.9 +/- 0.6 ng/g (p < 0.05 vs control).
      Although baseline histamine contents were 10-fold higher in rats, PC also had no
      effect, but compound 48/80 reduced content by 91%. Therefore, histamine tissue
      content and presumably mast cell granules were unaffected by a PC protocol which
      successfully protected ischemic myocardium, while pharmacological myocardial
      histamine depletion was not associated with protection. Hence, mast cells do not
      appear to be important in ischemic preconditioning. Although a mast cell
      stabilizer such as DSCG can protect ischemic myocardium, it may do so by one of
      its other properties, e.g., membrane stabilization.

PMID- 8996632
TI  - Systolic coronary flow reduction in the canine heart in situ: effects of left
      ventricular pressure and elastance.
AB  - In the externally perfused coronary bed of the isolated heart, LV elastance (Elv)
      rather than LV pressure (Plv) appears to be the major factor responsible for
      systolic coronary flow reduction, although effects of both have been
      demonstrated. However, normal perfusion in the presence of intact autoregulation
      in the heart in situ may modify these effects. To investigate the systolic
      coronary flow (Qsyst) responses to changes in end-systolic Elv and in systolic
      Plv in the intact coronary bed, we studied 7 anesthetized dogs. Dogs were
      vagotomized, paced and instrumented with Doppler flow probes. Elv, obtained from
      micromanometer- and conductance-catheters, was changed by dobutamine infusion (10
      micrograms/kg/min) and characterized by its slope (Ees) and volume position at 15
      kPa (V15). Plv was changed stepwise by volume loading. Correction for metabolism
      induced changes in Qmean was made. Thus, we found that dobutamine increased Ees
      by 44% (p < 0.0001), decreased V15 by 43% (p < 0.0001), and reduced corrected
      Qsyst significantly (p < 0.001) from 22.8 to 13.8 ml/min, while Plv (9.5-19.5
      kPa) did not affect corrected Qsyst (p > 0.5). We conclude that systolic coronary
      flow reduction is related to both elastance parameters, Ees and V15, and not to
      Plv in the normally perfused canine heart in situ.

PMID- 8996634
TI  - Preparation of a monoclonal antibody specific for 5-methyl-2'-deoxycytidine and
      its application for the detection of DNA methylation levels in human peripheral
      blood cells.
AB  - A monoclonal antibody specific for a modified nucleoside, 5-methyl-2'
      deoxycytidine (m5dCyd), was prepared using 5-methylcytidine (m5Cyd)-keyhole
      limpet haemocyanin (KLH) conjugate, and was characterized. Termed FMC9, the
      antibody reacts with m5dCyd and slightly with m5Cyd and 5-methylcytosine (m5Cyt)
      but not with other nucleosides tested in this investigation. FMC-9 was used in an
      enzyme-linked immunosorbent assay (ELISA) system for the quantitation of m5dCyd
      levels. Sensitivity was in the picomole range. Methylation levels in peripheral
      blood cells of healthy donors were determined by inhibition ELISA. The percentage
      of m5dCyd in peripheral blood cells of 10 healthy donors was 5.08 +/- 0.50%.
      These results suggest that the inhibition ELISA using FMC9 is useful to monitor
      m5dCyd levels in the peripheral blood cells.

PMID- 8996633
TI  - Inotropic reserve and histological appearance of hibernating myocardium in
      conscious pigs with ameroid-induced coronary stenosis.
AB  - Inotropic reserve, demonstrated with administration of sympathomimetic amines, is
      characteristic of hibernating myocardium. The goal of this study was to determine
      whether inotropic reserve was present following chronic coronary artery
      constriction in the pig, which is one potential model of hibernating myocardium.
      The effects of isoproterenol were examined in five conscious pigs 21 +/- 2.1 days
      after ameroid implantation on the left circumflex coronary artery on measurements
      of left ventricular (LV) pressure, LV dP/dt, and regional wall thickening in the
      ameroid-dependent zone (posterior wall) and contralateral non-ischemic zone
      (anterior wall). Isoproterenol, 0.1 microgram/kg/min, increased LV dP/dt by 96 +/
      11%, heart rate by 43 +/- 13 beats/min, and normalized systolic wall thickening,
      slightly, but not significantly more in the ameroid-dependent zone (+1.57 +/-
      0.31 mm) than in the contralateral non-ischemic zone (+1.04 +/- 0.31 mm),
      although the baseline wall thickening was reduced significantly in the ameroid
      dependent zone. This occurred at a time when baseline myocardial blood flow was
      preserved and myocardial perfusion in the ameroid-dependent zone was derived in
      part from the native coronary circulation and also through collateral channels.
      Two weeks later histological evidence of lesions characteristic of hibernating
      myocardium, i.e., myofibrolysis and increased glycogen deposition, were observed.
      Thus, these histological changes and the confluence of chronically depressed
      regional function and residual inotropic reserve in the conscious pig with
      chronic ameroid-induced coronary constriction support this model for further
      study of hibernating myocardium.

PMID- 8996636
TI  - Purification and characterization of alpha-L-rhamnosidase from Bacteroides JY-6,
      a human intestinal bacterium.
AB  - An alpha-L-rhamnosidase (EC 3.2.1.40) was purified 1500-fold from Bacteroides JY
      6, an intestinal anaerobic bacterium of human. The specific activity of purified
      enzyme was 89.9 mumol/min/mg protein. The enzyme (M.W. 240000) is composed of two
      subunits of M.W. 120000 with pI and optimal pH values of 4.2 and 7.0,
      respectively. The apparent Kms for naringin, rutin and p-nitrophenyl-alpha-L
      rhamnopyranoside were determined to be 0.89, 1.44 and 0.29 mM, respectively. The
      enzyme was strongly inhibited by L-rhamnose, L-fucose, saccharic acid 1,4
      lactone, p-chlormercuriphenylsulfonic acid and Pb2+.

PMID- 8996635
TI  - Molecular cloning of a complementary DNA for a membrane cofactor protein (MCP,
      CD46)/measles virus receptor on Vero cells and its functional characterization.
AB  - We isolated a 1257-bp cDNA encoding a membrane cofactor protein (MCP,
      CD46)/measles virus (MV) receptor-like protein from a cDNA library of Vero cells,
      in which wild MV strains were established. Vero cells contain MCP mRNA splice
      products encoding different cytoplasmic tails like human cells. The deduced amino
      acid sequence of the cDNA was 86% identical to that of human MCP. Vero cell MCP
      expressed on CHO cells was recognized by monoclonal antibodies against human MCP,
      and served as a potent MV receptor. In addition, Vero MCP was as effective as
      human MCP in human factor I-mediated C3b cleavage. Thus, the high MV
      susceptibility of Vero cells can in part be attributed to an MCP-like molecule
      that is structurally and functionally similar to human MCP.

PMID- 8996637
TI  - Characterization of poly-leucine substituted analogues of the human surfactant
      protein SP-C.
AB  - A series of novel amphipathic peptides constituted of an N-terminal hydrophilic
      portion (CPVHLKR, residues 6-12) of human pulmonary surfactant protein-C (SP-C)
      and a poly-leucine (poly-L) stretch of various chain lengths as the C-terminal
      hydrophobic tail were synthesized and evaluated relevant to their ability to
      improve the surface activity of a ternary lipid mixture composed of
      dipalmitoylphosphatidylcholine, egg-phosphatidylglycerol and palmitic acid
      (DPPC/E-PG/PA, 75:25:10, w/w) in a Langmuir-Wilhelmy surface balance. CPVHLKRL11,
      a human SP-C analogue bearing an 11-residue poly-L tail, and its related peptides
      with longer tails in the ternary lipid mixture, accelerated not only the surface
      spreading at the air-water interface but also exhibited significantly improved
      dynamic surface activity, compared to the ternary lipid mixture. Their surface
      activities were almost indiscernible from those of the synthetic human SP-C. When
      reconstituted into a ternary lipid mixture containing members of the homologous
      series of n-saturated diacylphosphatidylglycerol, the surface activities of the
      poly-L analogues were almost completely unaffected, whereas replica peptides
      carrying the hydrophobic portion of native SP-C were found to have distinct
      surface activities depending upon the acyl-chain lengths of phosphatidylglycerol.
      The poly-L stretch of a poly-L analogue could be replaced with poly-norleucine of
      the same chain length without a significant loss of surface activity.
      Substitution of the poly-L portion in the analogues with poly-valine or poly
      isoleucine resulted in a considerable decrease in surface activity. The poly-L
      analogue in the DPPC/E-PG/PA mixture was demonstrated to act as an excellent
      surfactant comparable with Surfacten, a modified bovine surfactant preparation
      that was used for treatment for infant respiratory distress syndrome, based on
      evaluation of the lung pressure-volume characteristics using premature rabbit
      neonates.

PMID- 8996638
TI  - Role of stearoyl-CoA desaturase in the modification of acyl composition of
      hepatic phosphatidylcholine by peroxisome proliferators.
AB  - The relative contribution of stearoyl-CoA desaturase and 1
      acylglycerophosphocholine (1-acyl-GPC) acyltransferase, which are induced by
      peroxisome proliferators, to the increase in the proportion of oleic acid in C-2
      position of phosphatidylcholine (PtdCho) in the liver of rats was investigated.
      Rats were administered either 4-chlorophenoxyisobutyric acid (clofibric acid),
      2,2'-(decamethylenedithio)-di-ethanol (tiadenol) or perfluorooctanoic acid in
      varying doses. With administration of these peroxisome proliferators, the
      proportion of oleic acid in C-2 position of PtdCho in hepatic microsomes was
      increased in commensurate with the increase in activities of stearoyl-CoA
      desaturase and 1-acyl-GPC acyltransferase. Multiple regression analysis revealed
      that although there is a high correlation among the three parameters examined,
      the partial correlation between the proportion of oleic acid in the C-2 position
      and the activity of stearoyl-CoA desaturase is significantly higher than that
      between the proportion of oleic acid in the C-2 position and the activity of 1
      acyl-GPC acyltransferase. The contribution of stearoyl-CoA desaturase to the
      increase in the proportion of oleic acid in the C-2 position thus appears greater
      than that of 1-acyl-GPC acyltransferase.

PMID- 8996639
TI  - Intracellular pH regulation of newborn rat skin basal cells.
AB  - The regulation of intracellular pH (pHi) was examined in newborn rat skin basal
      cells. When basal cells were acid-loaded by externally applied weak acid or by
      pretreatment with NH4+, the pHi recovered toward its resting value. This recovery
      was accompanied by Na+ influx and H+ efflux. The recovery of pHi and concomitant
      Na+/H+ fluxes were reversibly inhibited by amiloride. Other ionic flux inhibitors
      4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and furosemide slightly
      inhibited the pHi recovery from an acid load. The recovery rate from an acid load
      depended on the concentration of the external Na+.Li+ could substitute for Na+ in
      the pHi recovery, but K+ had no effect on the recovery. The keratin synthesis of
      basal cells was decreased by amiloride, and this decrement was deduced to be due
      to the acidification of the intracellular space. Although ascorbic acid had no
      effect on the pHi recovery of basal cells, it enhanced the keratin synthesis of
      the cells. Moreover, an inhibitor of the collagen synthesis, cis-hydroxyproline,
      suppressed the keratin synthesis but had no effect on the pHi recovery. We
      therefore believe that the keratin synthesis of the cells was also regulated by
      the environment, which was formed by the synthesized collagen. Thus, the pHi in
      the skin basal cells was regulated by the amiloride-sensitive exchange system,
      and this system seems to be involved in the keratin synthesis.

PMID- 8996640
TI  - A new method for permeabilization of the plasma membrane of cultured mammalian
      cells. VII. Permeabilization of growing and resting cells by vortex-stirring with
      high molecular weight polyacrylic acid.
AB  - The permeability of murine leukemia L1210 cells toward non-permeant fluorescent
      Lucifer Yellow (LY) was evaluated by flow cytometry following vortex-stirring of
      cells with LY in the presence of high molecular weight polyacrylic acid (A-119).
      Permeabilization by this technique was greatly enhanced in growth phase cells,
      whereas it was appreciably reduced in resting cells which had been maintained in
      unchanged culture medium for 2 to 4d. This reduction in permeabilization of
      resting cells gradually disappeared when resting cells were re-suspended in fresh
      culture medium, and the degree of permeabilization was restored to that of the
      growing cells. It is recommended that the mammalian cells used for
      internalization of non-permeant materials by vortex-stirring with A-119 should be
      in the early log phase.

PMID- 8996641
TI  - Suppression of hyperlipidemia-associated cataracts in diabetic rats with the
      lipoprotein lipase activator NO-1886.
AB  - Diabetic cataracts are thought to be caused by hyperglycemia associated with
      disturbed glucose metabolism. Diabetes mellitus often involves abnormal lipid
      metabolism in addition to abnormal glucose metabolism. To date, however, very few
      studies have counted hyperlipidemia as a risk factor for diabetic cataracts. The
      present study was undertaken to determine whether this actually is a risk factor
      for diabetic cataracts and to confirm that the onset of cataracts associated with
      diabetes mellitus can be suppressed by correction of hyperlipidemia. When rats
      with streptozotocin (STZ)-induced diabetes mellitus were fed an ordinary diet,
      cataracts became evident at 9 weeks in 26.7% of animals, and increased to an
      incidence of 73.3% after 10 weeks of STZ treatment. However, in rats with STZ
      induced diabetes mellitus that were fed a cholesterol rich diet to induce severe
      hyperlipidemia, cataracts were observed one week earlier, after 8 weeks of
      treatment, in 36.0% of animals, with an increase to a 52.0% incidence and a 76.0%
      incidence after 9 and 10 weeks of STZ treatment, respectively. Hyperlipidemia was
      therefore associated with an earlier onset and an elevated incidence of diabetic
      cataracts. When the lipoprotein lipase (LPL) activator NO-1886 was administered
      to diabetic rats which had developed severe hyperlipidemia, they showed a
      decrease in plasma total cholesterol, triglyceride and non-high density
      lipoprotein (non-HDL)-cholesterol levels and an increase in high density
      lipoprotein (HDL)-cholesterol level, and the onset of diabetic cataracts was
      markedly suppressed. The results of this study suggest that hyperlipidemia and
      low HDL-cholesterol levels may be risk factors for the onset of diabetic
      cataracts, and that this onset can be suppressed if measures are taken to
      alleviate these risk factors. The LPL activator NO-1886 may be useful in
      preventing the onset of diabetic cataracts.

PMID- 8996642
TI  - Amino acids and peptides. XXIX. Synthesis and antimetastatic effects of peptides
      and peptide-poly(ethylene glycol) hybrids related to the core sequence of the
      type III connecting segment domain of fibronectin.
AB  - Peptides (H-Glu-Ile-Leu-Asp-Val-NH2, H-Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr-NH2, H-Arg
      Glu-Asp-Val-NH2) and their poly(ethylene glycol) (PEG) hybrids related to the
      core sequence of the type III connecting segment domain of fibronectin A chain
      were prepared by the solution method or the solid phase method. Their inhibitory
      effects on the adhesion and migration of B16-BL6 melanoma cells to fibronectin
      were assessed in vitro, and their therapeutic potency against tumor metastasis
      were also examined. Anti-adhesive and anti-migrative effects of the synthetic
      fibronectin-related peptids were superior to those of their PEG hybrids, so we
      found that the in vitro bioactivity of peptides decreased by PEGylation. In the
      in vivo assay, we found that the synthetic peptides containing Glu-Ile-Leu-Asp
      Val and Arg-Glu-Asp-Val sequences exhibited an inhibitory effect on the
      experimental metastasis of B16-BL6 melanoma. Of the synthetic peptides, H-Glu-Ile
      Leu-Asp-Val-NH2 exhibited the most potent inhibitory effect. Hybrid formation of
      Arg-Glu-Asp-Val with poly(ethylene glycol) resulted in potentiation of the
      inhibitory effect of the parent peptides. A mixture composed of PEG hybrids of
      Glu-Ile-Leu-Asp-Val, Arg-Glu-Asp-Val and Tyr-Ile-Gly-Ser-Arg dramatically
      inhibited tumor metastasis.

PMID- 8996643
TI  - Antioxidative effects of phenylethanoids from Cistanche deserticola.
AB  - The acetone-H2O (9:1) extract from the stem of Cistanche deserticola showed a
      strong free radical scavenging activity. Nine major phenylethanoid compounds were
      isolated from this extract. They were identified by NMR as acteoside,
      isoacteoside, 2'-acetylacteoside, tubuloside B, echinacoside, tubuloside A,
      syringalide A 3'-alpha-rhamnopyranoside, cistanoside A and cistanoside F. All of
      these compounds showed stronger free radical scavenging activities than alpha
      tocopherol on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and xanthine/xanthine
      oxidase (XOD) generated superoxide anion radical (O2-.). Among the nine
      compounds, isoacteoside and tubuloside B, whose caffeoyl moiety is at 6'-position
      of the glucose, showed an inhibitory effect on XOD. We further studied the
      effects of these phenylethanoids on the lipid peroxidation in rat liver
      microsomes induced by enzymatic and non-enzymatic methods. As expected, each of
      them exhibited significant inhibition on both ascorbic acid/Fe2+ and
      ADP/NADPH/Fe3+ induced lipid peroxidation in rat liver microsomes, which were
      more potent than alpha-tocopherol of caffeic acid. The antioxidative effect was
      found to be potentiated by an increase in the number of phenolic hydroxyl groups
      in the molecule.

PMID- 8996644
TI  - Effect of streptozotocin-induced diabetes on cyclosporin A disposition in rats.
AB  - We studied the effect of diabetes on the pharmacokinetics of cyclosporin A (CyA)
      after intravenous and oral administration of CyA using the plasma and lymph of
      streptozotocin (STZ)-induced diabetic rat. There were no significant differences
      in the systemic and lymphatic availabilities after intravenous administration of
      CyA in diabetic rats compared with those of the controls. On the other hand,
      systemic and lymphatic availabilities after oral administration of CyA were
      significantly different in diabetic rats compared to those in the controls. These
      results suggest that the pharmacokinetics of CyA, particularly absorption, were
      altered in diabetic rats. Gastrointestinal transit in diabetic rats was also
      studied. The gastric emptying rate in diabetic rats was enhanced compared with
      that of the controls, but small intestinal transit was reduced in diabetic rats,
      suggesting that a change in gastrointestinal transit in diabetic rats may
      influence the absorption of CyA. The increased absorption of CyA from the
      digestive tract of diabetic rats altered not only the systemic availability but
      also the lymphatic availability, suggesting that altered systemic availability
      may cause adverse effects and that altered lymphatic availability may influence
      the immunosuppressive effects.

PMID- 8996646
TI  - Pharmacokinetic study of taxol-loaded poly(lactic-co-glycolic acid) microspheres
      containing isopropyl myristate after targeted delivery to the lung in mice.
AB  - This study describes the pharmacokinetic behaviours of taxol after intravenous
      administration of taxol-loaded poly(lactic-co-glycolic acid) microspheres
      containing isopropyl myristate (namely, Taxol-IPM-PLGA-MS) and taxol saline
      solution to mice. Taxol-IPM-PLGA-MS were prepared using a solvent evaporation
      technique. The drug content and trapping efficiency of taxol in the microspheres
      were 5.09% (w/w) and 98%, respectively; the average diameter of the microspheres
      was 30.1 microns. Scanning electron microscopy showed that Taxol-IPM-PLGA-MS were
      spherical with a smooth surface. After administration of the drug saline solution
      (3 mg taxol/kg), taxol disappeared rapidly from plasma within 4-6 h and
      distributed extensively in various tissues. The tissue levels and AUCfinite of
      taxol in the lung were obviously higher than those in plasma but relatively lower
      than those in kidneys, bile, and liver. The biodistribution of taxol after
      administration of Taxol-IPM-PLGA-MS (3 mg taxol/kg), on the other hand, was
      altered significantly from the control (taxol solution) group. No taxol was
      detected in plasma or bile within 3 weeks, and only very low level of taxol was
      detected in the kidneys or liver within 48 h. However, taxol concentrations in
      the lung were increased significantly with the microsphere group; the peak
      concentration of taxol and AUCfinite in the lung was three times and 500 times
      higher than those with the taxol solution group, respectively. It was also
      noticed that the taxol levels in the lung were maintained at relatively high
      levels (> 10 micrograms/ml) for 3 weeks. Thus, the present study demonstrated the
      effective targeted delivery of taxol to the lung of mice using Taxol-IPM-PLGA-MS.

PMID- 8996645
TI  - Inhibition of theophylline metabolism by aciclovir.
AB  - We report a case of side effects caused by the increase in plasma theophylline
      concentration after coadministration of aciclovir had been started during
      theophylline therapy. Interaction between theophylline and aciclovir has not
      previously been reported. Therefore, a study of the pharmacokinetic and metabolic
      interactions between theophylline and aciclovir was carried out in five healthy
      male volunteers. All subjects received a single oral dose of 320 mg theophylline
      (aminophylline, 400 mg) after they had taken oral aciclovir 800 mg five times
      daily for two consecutive days. The area under the curve from 0 to infinity of
      theophylline (AUC0-infinity) after coadministration of aciclovir was increased
      from 189.9 +/- 18.2 to 274.9 +/- 34.3 micrograms.h/ml (p < 0.01), and total body
      clearance was decreased from 28.4 +/- 2.9 to 19.8 +/- 2.5 ml/h/kg (p < 0.01).
      Further, there was a significant increase in urinary theophylline and decreases
      in urinary 1,3-dimethyluric acid and 1-methyluric acid after coadministration of
      aciclovir. The decrease in total body clearance is likely to have resulted from
      inhibition of metabolism via the oxidation pathway. The results indicated that
      with aciclovir therapy lower doses of theophylline might be necessary and careful
      monitoring of plasma concentrations was essential.

PMID- 8996647
TI  - Synthesis and biological activity of four kinds of reversed peptides.
AB  - We have synthesized four kinds of reversed peptides of various physiologically
      active peptides, which inhibit TNF (tumor necrosis factor) cytotoxicity, produce
      NGF (nerve growth factor), exert antimicrobial activity and inhibit cell
      attachment, respectively. They were examined for their biological activity in
      comparison with that of normal peptides, that is, naturally occurring peptides.
      The reversed peptides induce similar activities, but to a lesser extent than
      those of the normal peptides, respectively. These results indicate that there may
      be conformationally ambiguous binding in some of the naturally occurring ligand
      protein interactions. This method may be useful as a tool to rapidly generate a
      novel lead peptide with the desired biological function from a naturally
      occurring active peptide.

PMID- 8996648
TI  - Hydroxyl radical scavenging activity of naturally occurring furan fatty acids.
AB  - As a part of our work on the antioxidant properties of naturally occurring furan
      fatty acids (F acids), we evaluated their hydroxyl radical (HO.) scavenging
      activity by an electron spin resonance (ESR) spin trapping technique with 5,5
      dimethyl-1-pyrroline-N-oxide (DMPO). The additions of F acids to the incubation
      mixture of Fe2(+)-diethylenetriaminepentaacetic acid complex, H2O2 and DMPO
      decreased the intensity of the DMPO-OH adduct signal in a dose-dependent way.
      This decrease was not attributed to the destruction of DMPO-OH adduct by F acids.
      Kinetic competition studies indicated that the decrease in DMPO-OH signal
      intensity was mainly due to the competition of F acids with DMPO for HO., and not
      to the inhibition of the HO. generation system itself. F acids were found to
      react rapidly with HO. at approximately a diffusion-controlled rate (1.7 x
      10(10)M-1 s-1). Comparison with the common HO. scavengers indicated that the rate
      constant of F acids is higher than those of mannitol and ethanol, and is
      compatible with those of histidine and dimethylsulfoxide, demonstrating that F
      acids are a potent HO. scavenger. It is suggested that F acids may serve as
      antioxidants in biological systems through their ability to scavenge HO..

PMID- 8996649
TI  - A protein kinase C inhibitor NA-382 prolongs the life span of AH66F-bearing rats
      as well as inhibiting leukocyte function-associated antigen-1 (LFA-1)-dependent
      adhesion of the cells.
AB  - Rat ascites hepatoma AH66F is a high malignant tumor line, and AH66F-bearing rats
      died about 10 d after tumor inoculation. When treated with a protein kinase C
      (PKC) inhibitor, NA-382, the life span of AH66F-bearing rats was significantly
      prolonged, while a potent protein kinase A inhibitor, H-89, was not effective. In
      the adhesion assay, the adhesive ability to the mesentery-derived mesothelial
      cells (M-cells) of AH66F cells from rats injected with 10 mg/kg of NA-382 was
      significantly decreased, while the adhesion rate of the cells from the vehicle
      control group and from the H-89 (10 mg/kg)-treated group was about 50%. The
      adhesion of AH66F cells from the vehicle control group was curtailed to one half
      by leukocyte function-associated antigen-1 (LFA-1) beta-chain monoclonal antibody
      (WT.3), but that from the NA-382 group was not further influenced by WT.3. In
      flow cytometric analysis using WT.3, the expression of LFA-1 beta-chain on AH66F
      cells from the NA-382-treated group was also partially decreased, while that from
      the H-89-treated group was not changed. It was confirmed in vitro that after
      treatment with these protein kinase inhibitors for 48 h the expression of LFA-1
      beta-chain in the cells was decreased by NA-382, but not by H-89. These results
      suggested that the PKC inhibitor prolongs the life span of AH66F-bearing rats
      through inhibition of LFA-1-dependent adhesion of the cells.

PMID- 8996650
TI  - Examination of stability of anticonvulsants in a protease solution and assay of
      anticonvulsants in hairs.
AB  - For analyzing the concentrations of drugs in hairs, a new method of digestion of
      hairs with Biopurase, a protease obtained from Bacillus subtilis, was examined.
      The concentrations of drugs in hairs were then determined in order to examine the
      usefulness of the protease for the digestion of hairs. The stability of five
      anticonvulsants in the protease solution was maintained over a 12-h period. In
      the clinical tests, the concentrations of the drugs in hairs obtained from
      patients who were taking anticonvulsants for a long time were determined. The
      concentration of phenobarbital in hairs in 10 patients taking phenobarbital
      ranged from 194 to 5020 ng/10 mg with a mean of 578 ng/10 mg, and the
      concentration of phenytoin in hairs in 6 patients taking phenytoin ranged from 44
      to 299 ng/10 mg with a mean of 115 ng/10 mg. From these results, the transfer of
      phenobarbital and phenytoin from circulating blood into hairs was confirmed, and
      the usefulness of Biopurase for the digestion of hairs was proved.

PMID- 8996651
TI  - Effectiveness and toxicity screening of various absorption enhancers in the large
      intestine: intestinal absorption of phenol red and protein and phospholipid
      release from the intestinal membrane.
AB  - The effectiveness and local toxicity of absorption enhancers on the absorption of
      phenol red (PR) from the large intestine of rats were examined using an in situ
      loop method. The absorption enhancers used in this study were sodium glycocholate
      (GC-Na), sodium taurocholate (TC-Na), sodium deoxycholate (DC-Na), EDTA, sodium
      salicylate (Sal-Na), sodium caprate (Cap-Na), diethyl maleate (DM), N-lauryl-beta
      D-maltopyranoside (LM) and mixed micelles (MM), all used at a concentration of 20
      mM. Local toxicity was also investigated by assessing protein and phospholipid
      release as biological markers. DC-Na and MM were the most effective absorption
      enhancers, but they caused considerable release of proteins and phospholipids. GC
      Na, TC-Na and LM, which caused little or only slight membrane damage, promoted PR
      absorption. Sal-Na, DM and EDTA did not enhance PR absorption. Overall, a
      correlation exists between the area under the curve of PR and protein and
      phospholipid release in the presence of absorption enhancers. However, GC-Na, TC
      Na and LM promoted the absorption of PR with low toxicity. From these results, we
      concluded that GC-Na, TC-Na and LM are effective absorption enhancers which have
      low levels of toxicity at a concentration of 20 mM.

PMID- 8996653
TI  - Collagen and glycosaminoglycans of Wharton's jelly.
AB  - In this study, we report quantity, solubility and molecular polymorphism of
      collagen, proportional relationships between various types of collagen,
      ultrastructure of collagen fibres, the amounts of various glycosaminoglycans
      (GAGs) and proportional relationships between them in Wharton's jelly of normal
      umbilical cords. We compare the extracellular matrix components in Wharton's
      jelly with those in the umbilical cord artery. Collagen of the Wharton's jelly
      demonstrates some specific features. It is very insoluble in neutral salt and in
      a slightly acidic solution and appears to be resistant to the action of
      depolymerizing agent (EDTA-Na2). Only 50% of total collagen may be solubilized by
      pepsin digestion and fractionated by differential salt precipitation. Four
      collagen fractions were obtained. Three of them were identified by polyacrylamide
      gel electrophoresis as type I, type III, and type V collagen and proportional
      relationship between them was calculated. Hyaluronic acid is the most abundant
      component of GAGs contained in Wharton's jelly. The amounts of sulphated GAGs
      keratan sulphate, heparan sulphate, chondroitin-4-sulphate, chondroitin-6
      sulphate, dermatan sulphate and heparin-are distinctly lower. Each of them
      constitutes only a few percent of total GAGs.

PMID- 8996652
TI  - Risk factors of sensorineural hearing loss in preterm infants.
AB  - Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and
      1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural
      hearing loss. Perinatal risk factors of infants with hearing loss were compared
      with those of two control groups matched for gestation and birth weight and for
      perinatal complications. Our observations demonstrated an association of hearing
      loss with a higher incidence of perinatal complications. Ototoxicity appeared
      closely related to a prolonged administration and higher total dose of ototoxic
      drugs, particularly aminoglycosides and furosemide. Finally, we strongly
      recommend to prospectively and regularly perform audiologic assessment in sick
      preterm children as hearing loss is of delayed onset and in most cases bilateral
      and severe.

PMID- 8996654
TI  - Relationship between intrauterine growth retardation and early postnatal superior
      mesenteric artery blood flow velocity.
AB  - During the first week of life, we examined the changes in the systemic,
      intestinal and cerebral circulation, and the circulatory responses to feeding in
      10 small for gestational age (SGA) infants using the ultrasound Doppler
      technique. From day 1 to day 3, preprandial cardiac output decreased (p < 0.01),
      whereas mean blood pressure (p < 0.01), superior mesenteric artery mean flow
      velocity (Vmean; p < 0.01) and middle cerebral artery Vmean (p < 0.01) increased.
      On day 1, cardiac output was higher in the SGA than in those of term and preterm
      appropriate for gestational age infants reported from our laboratory. Preprandial
      superior mesenteric artery Vmean was inversely related to the degree of growth
      retardation (r = 0.63, p < 0.05). However, growth retardation did not influence
      the postprandial increase in superior mesenteric artery Vmean and end-diastolic
      flow velocity, or the cerebral circulation.

PMID- 8996655
TI  - Brain stem auditory-evoked response in relation to neonatal glucose metabolism.
AB  - Imprecise control of glucose homeostasis is a hallmark of neonatal glucose
      metabolism. A relatively wide range of glucose concentrations is considered
      'euglycemic' (2.22-6.94 mmol/l, 40-125 mg/dl) in the neonatal period. We
      investigated the effects of a wide range of glucose concentrations on brain stem
      conduction time (BCT) I-V interpeak latency or prolonged wave V latency. Neonates
      were assessed by brain stem auditory-evoked response followed immediately by
      heelstick sampling to determine the blood glucose concentration. Twenty-seven
      appropriate for gestational age (AGA) term neonates (birth weight 3,245 +/- 766
      g, mean +/- SD; gestational age 39 +/- 2 weeks) were studied 3.1 +/- 3.7 days
      after birth. Twenty-three AGA preterm neonates (birth weight 2,175 +/- 477 g;
      gestational age 35 +/- 1 weeks) were studied 6.0 +/- 7.2 days after birth. Brain
      stem conduction time wave I-V interpeak latency and wave V latency were
      determined in two trials using a Grason-Stadler ABR screener at a 60-decibel
      stimulation level in the right ear. Neonates were studied between 33 and 40 weeks
      gestational age. Although the blood glucose concentration ranged from 1.38 to
      6.83 mmol/1 (25-123 mg/dl), there was no correlation between either brain stem
      conduction time wave I-V interpeak latency or wave V latency and blood glucose
      concentration. We conclude that alterations in glucose concentration within the
      generally accepted neonatal euglycemic range do not effect the functional status
      of the brain stem auditory pathway. We suggest that the data can be interpreted
      to affirm that tighter clinical control of glucose homeostasis is probably not
      required in the neonatal period.

PMID- 8996656
TI  - Salt supplementation, growth, and nephrocalcinosis in the furosemide-treated
      weanling rat.
AB  - OBJECTIVE: Furosemide treatment in the human neonate is associated with sodium
      depletion, growth retardation, hypercalciuria and nephrocalcinosis. Dietary
      sodium intake is known to directly influence urinary calcium excretion. The
      objectives of this study were to create a rat model of furosemide-induced
      nephrocalcinosis and to test the effects of dietary sodium supplementation on
      growth, electrolyte balance, calciuria, and renal calcifications. METHODS:
      Initially, 18 weanling Sprague-Dawley rats were randomly divided into three
      groups. Groups A (control) and B were fed a basal diet. Group C was fed a sodium
      enriched diet. Groups B and C received furosemide (40 mg/kg) intraperitoneally
      daily for 28 days. At the end of the study, serum, urine, and kidney samples were
      obtained for biochemical and histologic analyses. The three groups were then
      compared for differences in growth, electrolyte homeostasis, calcium excretion
      and nephrocalcinosis. Subsequently an additional 15 rats were studied to confirm
      our findings regarding urinary calcium excretion and kidney calcifications.
      RESULTS: Treatment with furosemide without sodium supplementation (group B)
      resulted in decreased weight gain compared with group A (137.5 +/- 12.9 vs 154.0
      +/- 10.6 g; p < 0.05), hypokalemia (3.7 +/- 0.1 vs. 4.4 +/- 0.4 mEq/l; p < 0.05),
      and nephrocalcinosis (187.1 +/- 155 vs. 18.8 +/- 6.9 micrograms Ca/g dry kidney;
      p < 0.05). Sodium supplementation (group C) normalized weight gain and corrected
      electrolyte abnormalities without increasing calciuria or nephrocalcinosis.
      CONCLUSIONS: We conclude that in this animal model, chronic furosemide treatment
      results in growth failure and development of nephrocalcinosis. Sodium
      supplementation protects against the deleterious effects of furosemide on weight
      gain and electrolyte homeostasis with no adverse effect on nephrocalcinosis.

PMID- 8996657
TI  - Interleukin-1 alpha upregulates the expression of surfactant protein-A in rabbit
      lung explants.
AB  - Interleukin-1 (IL-1) is an important participant in infectious and inflammatory
      conditions. Interleukin-1 receptor antagonist (IL-1ra) prevents the effect of IL
      1. We have shown that injection of interleukin-1 alpha (IL-1 alpha) into the
      amniotic fluid of pregnant rabbits stimulates the expression of surfactant
      protein-A (SP-A) in the lungs of the fetuses. We hypothesized that IL-1 alpha
      similarly enhances the expression of SP-A in rabbit lung explants in vitro.
      Explants obtained from 22-day fetal rabbit lungs were cultured in Waymouth's
      medium on a rotating platform in the presence or absence of IL-1 alpha (5.7-570
      ng/ml) or IL-1ra (1-10 micrograms/ml). Dibutyryl cAMP (1 mM) served as a positive
      control. After 3 days in culture, the explants were harvested and Northern
      analysis of SP-A was performed using the 1.9-kb rabbit SP-A cDNA probe. IL-1
      alpha and dibutyryl cAMP increased the expression of SP-A twofold, as judged by
      video densitometry. IL-1ra did not change SP-A expression as compared with
      controls, suggesting that endogenous IL-1 activity was not responsible for the
      basal level of SP-A expression in the explants. Dibutyryl cAMP increased the
      expression of SP-B mRNA, whereas IL-1 alpha had no effect on SP-B mRNA
      concentration. We conclude that inflammatory mediators interact with lung cells
      to alter synthesis of important components of the surfactant system.

PMID- 8996658
TI  - Whole body lean mass is altered by dexamethasone treatment through reductions in
      protein and energy utilization in piglets.
AB  - The objective of this study was to assess the effect of dexamethasone on growth,
      body composition and protein metabolism using the piglet as a model for rapidly
      growing premature infants. Seven-day-old male pigs (n = 18) were randomized to
      0.5 mg/kg/day oral dexamethasone or placebo for 15 consecutive days. Weight and
      length gains and weight gained per energy or protein consumed were significantly
      lower in the dexamethasone group. Serum urea nitrogen was significantly higher in
      the dexamethasone group by day 15 of the study. No differences were observed
      between groups for urinary creatinine. The whole body percent lean mass was
      significantly lower and percent fat mass was significantly higher in the
      dexamethasone piglets, as measured by dual energy X-ray absorptiometry. In young
      piglets, dexamethasone, at doses similar to those in premature infants, induces
      protein catabolism, impairs growth and alters its composition.

PMID- 8996660
TI  - Use of IS6110 DNA fingerprinting in tracing man-to-man transmission of
      Mycobacterium tuberculosis in the Czech Republic.
AB  - The epidemiological relationship between tuberculosis cases in a prison and
      between cases within five families was investigated. Therefore, the isolated
      Mycobacterium tuberculosis strains were subjected to restriction fragment length
      polymorphism (RFLP) analysis using insertion sequence IS6110 as a probe. In case
      of 11 patients, the expected links of transmission were confirmed by RFLP typing.
      In contrast, in case of 4 patients the conclusion of classical contact tracing
      were not in agreement with the DNA fingerprinting results. These findings
      reinforce the usefulness of this recently developed technique as an additional
      tool in contact tracing. The IS6110DNA fingerprints of all strains investigated
      consisted of 7 to 13 bands and showed a high degree of polymorphism. Comparison
      of these fingerprints with those recorded in the Czech Republic previously,
      revealed the presence of a predominant DNA fingerprint type, without a known
      connection between the cases. Furthermore, other patterns found in the present
      study showed a high degree of similarity with the previously obtained
      fingerprints. Part of the patients were sampled twice. All of these double
      isolates showed identical fingerprints, confirming the previously described
      stability of IS6110DNA fingerprints. In contrast, from one couple of strains,
      isolated from husband and wife both suffering from tuberculosis, a slight change
      in one of the two patterns was observed. The patterns shared 10 band positions,
      confirming the expected relationship between these cases, but one of the patterns
      contained one additional band.

PMID- 8996659
TI  - In vitro regulation of insulin release and biosynthesis of fetal rat pancreatic
      cells explanted on pregnancy day 16.
AB  - Although the morphological development of the fetal pancreatic B cell has been
      studied in considerable detail, knowledge about the functional maturation,
      particularly in early stages of development, is still poor. The present paper
      describes a method for monolayer culture of fetal rat islet cells which allows a
      study of the regulation of insulin biosynthesis, release and content during
      critical stages of embryonic and fetal development. Suspensions of pancreatic
      cells were prepared from rat fetuses on pregnancy day 16 and cultured for 3 days.
      During the initial 2 days cultures were performed in the presence of 5 or 15
      mmol/l glucose. During this initial period, culture at 5 mmol/l glucose was
      carried out in the presence or absence of either 10 mmol/l nicotinamide (NA) or 5
      or 100 ng/ml nerve growth factor (NGF). After changing the media the cells were
      further exposed for 24 h to either 5 or 15 mmol/l glucose or 15 mmol/l glucose
      plus 5 mmol/l theophylline before measuring the insulin concentration in the
      culture medium. Cells that had initially been cultured for 2 days in 5 mmol/l
      glucose showed an increased insulin release, when subsequently cultured in 15
      mmol/l glucose for 24 h. Theophylline potentiated the response and caused a
      decrease in cellular insulin content. Cells initially cultured in the presence of
      15 mmol/l glucose showed unchanged insulin release during the subsequent 24-hour
      exposure to 15 mmol/l glucose, irrespective of the presence or absence of
      theophylline. The presence of NGF (100 ng/ml) during the initial 2-day culture
      period increased the insulin release in the presence of 15 mmol/l glucose and
      theophylline during the subsequent 24-hour culture period as compared to cells
      cultured in the absence of NGF. When cells were first exposed to either NA or NGF
      followed by exposure to 5 mmol/l glucose alone in the last 24-hour culture
      period, there was an increased insulin content. Rates of insulin biosynthesis
      remained unchanged irrespective of the glucose concentration in the culture
      medium. It is concluded that, already in early fetal development, B cells show
      glucose stimulation of insulin release albeit less pronounced than in the
      postnatal state.

PMID- 8996661
TI  - Immune response to exhaust gases derived from two-cycle combustion engine
      following experimental exposure.
AB  - Experimental exposures using laboratory Wistar rats inhaling the exhaust gases
      derived from a two-cycle combustion engine under the chamber conditions have been
      carried out. Immune response reflecting a burden of the respiratory system in the
      exposed animals following the respiratory exposure has been investigated. In
      variously designed exposure experiments, the dynamics of pulmonary alveolar
      macrophages (PAM) activity to phagocyte particular antigen (sheep red blood
      cells), the hemolysis production, the total serum complement level and the
      capacity of the pulmonary clearance from the inhaled silica dust have been
      examined. The findings revealed the depressed ability to produce antibodies
      against sheep red blood cells (SRBC) in case of prolonged animals exposure during
      the time-interval of antibodies production. PAM phagocytic activity decreased
      considerably as well, in the first phases of the SRBC phagocytosis. The total
      serum complement level was found to be decreased in consonance with the decreased
      hemolysins production. The pulmonary clearance from the inhaled silica particles
      was statistically significantly elevated in the animals exposed long-term before
      the dusting only. In case of the prolonged exposure during the lung clearance
      period of 25 days, the exposed animals did not show the difference anymore, if
      compared to the non-exposed group.

PMID- 8996662
TI  - Xenobiotics in food. I. Metabolic phthalate degradation.
AB  - In conjunction with the programme of monitoring the food contamination by one of
      the most widely distributed contaminants--phthalic acid esters--the present
      investigation was focused on the elucidation of metabolic transformations of
      phthalates in the organism of the rat and humans and on assessment of the
      phthalate content of beef and pork liver. As a model substance di-(2
      ethylhexyl)phthalate was selected. The paper contains new information on the
      mechanism of metabolic oxidative phthalate degradation in the rat, identifies the
      structure of intermediary products and suggests a reaction breakdown pattern. The
      balance of phthalate excretion from experimental animals in faeces and urine was
      examined, their metabolized ratio was defined and the phthalate load of the
      decisive parts of the organism was evaluated, i.e. in the liver, kidneys, spleen,
      brain and muscular tissue. Subsequent monitoring of phthalates in urine of human
      volunteers exposed only to the natural phthalate intake from contaminated food
      revealed the presence of some oxidative metabolites in body fluids. It provided
      also evidence of the possible endogenous formation of 2-ethyl-3
      carboxypropylphthalic acid the presence of which may signalize metabolic
      oxidation by a pathway terminated by possible hepatocellular carcinogenicity of
      phthalates. The probability of introduction of oxidative phthalate metabolites
      from meat of domestic animals seems minimal.

PMID- 8996663
TI  - Immunotoxic effects of carbon tetrachloride--the effect on morphology and
      function of the immune system in mice.
AB  - Carbon tetrachloride (CCL4), a polychlorinated hydrocarbon, is known for its
      hepatotoxicity, neurotoxicity and skin irritancy. Some epidemiological studies
      suggest possible carcinogenicity of CCl4. This substance is still present in
      industrial wastes and in the environment. As the major role of the immune system
      is immunosurveillance against cancer, we decided to follow the morphological and
      functional changes of the immune system during acute and subchronic exposures to
      CCL4 in mice. Mice (A/PhJ) were exposed i.p. to 1.7 mmol CCl4/kg b.w./day
      administered in olive oil (total volume 0.2 ml), for 2, 7, 14, 23 days. We
      evaluated: morphology of thymus, spleen and peripheral lymph nodes,
      immunopathology (thymus and spleen weight, spleen cellularity, number of
      peripheral blood leukocytes), non-specific immunity (phagocytosis, NK activity),
      humoral immunity (number of PFC after SRBC immunization, LPS mitogen response),
      cell-mediated immunity (PHA, ConA mitogen response). Morphological examination
      showed significant activation of lymphoid tissues in T-cell dependent areas. B
      cell areas were also activated, but the formation of active germinal centers in
      lymphatic follicles has not been observed. The natural immunity was affected in a
      time dependent manner. A slightly hepatotoxic dose of CCl4 had a significant
      stimulative effect on phagocytosis and natural killer activity when administered
      in short-term schedule ("acute exposure"). Subchronic administration of the same
      dose led to suppression of phagocytosis and Nk activity. Similarly, the
      lymphocyte response to non-specific mitogens was enhanced during short-term
      exposure and significantly impaired when CCl4 was administered in long-term
      schedule. Antigen specific immune response to SRBC was impaired immediately after
      short-term exposure to CCl4 which suggests that the substance might affect the
      immunoglobuline proteosynthesis at the cellular level.

PMID- 8996664
TI  - Impact of pesticides to groundwater resources in an alluvial plain using a
      geographical information system.
AB  - A methodology to evaluate the impact of pesticides to drinking water resources in
      an agricultural region has been applied in an Italian alluvial plain using a
      Geographical Information System (GIS). With this technology it is possible to
      store, process and represent geographical data and update them according to the
      environmental characteristics. The studied area, covering a surface of 500 km2,
      is located immediately south of Milan, in the alluvial plain of the Po river. The
      DRASTIC model (1) has been utilized in order to evaluate the intrinsic
      vulnerability of aquifers, DRASTIC is a quantitative method proposed by EPA to
      identify pollution potential especially referred to pesticides in USA. The
      application of this model, combined with data of land use has provided maps
      identifying areas at risk for groundwater pollution. Information derived from
      risk maps is of primary importance in territorial planning such as: selection of
      areas to be monitored, identification of areas to be protected, correct
      management of agricultural practices and use of pesticides. These maps should
      provide an useful instrument for agricultural and territorial management.

PMID- 8996665
TI  - Contribution to occupational angiopathy diagnosis using special examination
      method.
AB  - The authors presented 1642 cases of professional diseases caused by vibrations
      (VD) and 435 cases of extremity overload disease (EOD) diagnosed in the years
      1974-1993. In addition to the standard rheoplethysmography there were evaluated
      the results of digital laser Doppler flowmetry (Moor instruments, UK) in 104
      workers exposed to vibration (EV) and 25 controls with the age and smoking habit
      standardisation. In the selected subgroup were used continual measurements of
      digital blood pressure (Finapress, Ohmeda), digital LD flux and speed and the
      measuring of digital skin and central body temperature simultaneously. The
      records before and after 10 min of local cooling test (Rejsek method) and
      postocclusive hyperemic tests were summarized (computer evaluation, program
      STATGRAPHICS, T-test). Vasoconstriction to local cooling persisted in EV for
      longer time. The records of digital skin flux and speed, digital blood pressure
      reactions of EV were significantly different (EV/controls) also in the 10th min
      after cooling. Postocclusion hyperemic tests revealed good functional capacity
      also in EV. Advantages and disadvantages of methods were discussed. The results
      found by non-invasive methods in VD were in good relation to images obtained by
      means of radionuclides (clearance and cumulative tests). Cumulative tests (after
      99m--pertechnetate i.v.) can be used in the selected differential diagnostic
      cases of angiopathies to help to distinguish degree of angiospastic and
      angioparalytic changes in the hands of VD, and also in special cases at
      angiopathies connected with EOD.

PMID- 8996666
TI  - The dynamics of changes of upper extremities caused by vibrations and unilateral
      excessive load after discontinued risk exposure.
AB  - The main aim of our research was evaluation of changes affecting vessels and
      peripheral nerves of patients with disorder of the upper extremities caused by
      vibrations and also peripheral nerves due to excessive loads. We evaluated both
      groups of these patients after two and five years' discontinued exposure. During
      both examinations 90% of these subjects reported persistence or deterioration of
      their complaints. We found by objective examination of persons with disorders
      caused by an excessive load in 80% cases significant improvement of the
      neuropathy already after two years. But five years after absence from risk
      exposure we found only a slight further regression of disorders. In the group of
      patients with disorders caused by vibrations we found normalization of
      neurological changes after two years in 33%, but in 21% of these patients we
      proved progress to a more serious affections, however after five years there were
      almost no further changes. The vasospastic changes on vessels persist after two
      years in 83% and after five years in 51% of the examined patients. In both
      examined groups significant improvement of neural and vascular changes during the
      two years after absence from exposure was found. After five years only slight
      regression occurred.

PMID- 8996667
TI  - Reduction of the vibration of the hand-arm system by optimization of rotary
      hammer drills.
AB  - When operating a hand-held vibrating power tool, for example impact drills and
      rotary hammers, high vibration loads are introduced into the hand-arm system of
      the operator. In the long run these mechanical vibrations can lead to health
      problems of the hand-arm system. Hammer drilling tools for treatment of mineral
      materials are offered with many different designs of the cutting edge in the
      diameter range between 16 mm and 50 mm. In this research project the influences
      of the cutting edge design of drilling tools on the vibration characteristics of
      rotary hammers are investigated. The vibration exposure of the hand-arm system
      due to the tool and the volume of chip production are regarded. The gauge being a
      combination of the weighted acceleration and the drilling capacity. Based on the
      current spectrum of drillings tools neutral test have been developed to examine
      geometrical parameters. Both sets of drilling tools have been subjected to the
      same test programme. The analysis of the results led to the definition of the
      characteristics of an optimized rotary hammer drilling tool. Lists of criterions
      have been developed for the different groups of tools. Using these it is possible
      to create drilling tools optimized for vibration exposure. This was demonstrated
      by prototype drilling tools. The comparison of the results showed, that the
      averaged volume of chip production could be significantly improved by modifying
      the design of the drilling tools retaining the weighted acceleration. The
      comparison also showed that the total vibration severity parameter decreased.

PMID- 8996668
TI  - Hand-arm vibration hazard and prevention in China.
AB  - The status of the hand-arm vibration exposure and action for reducing vibration
      risk in China is outlined. The survey indicated that more than three million
      workers are exposed to hand-arm vibration. The vibration syndrome has been
      reported in sixteen provinces; over ten industries and twenty types of job. The
      measurement and assessment were conducted on twenty-four types of vibrating tools
      under normal working condition. The investigation of preventive measures is
      described, which includes the development of anti-vibration tools, improvement of
      technological processes, personal protection. A series of standards and
      regulations involving local vibration drawn up and published since 1980s is
      reviewed.

PMID- 8996669
TI  - Vibration reduction on hand-held grinders by automatic balancing.
AB  - By automatically balanced hand hold grinders, vibrations are reduced to at least
      half and thereby reducing the estimated risk for vibration injuries by a factor
      of four. Simultaneously less grinding disc consumption and better grinding
      results are obtained. Vibration from grinders originates mainly from unbalance in
      the grinding wheel. Grinding wheels are low price products. With uneven
      distribution of mass and coarse tolerances. This gives rise to out-of-balance,
      which changes as the wheel wears. By fitting an automatic balancer, that consists
      of steel balls contained in a cylindrical ball race on the shaft of the grinder,
      unbalances will be compensate for in the machine during grinding. The time it
      takes for an automatic balancer to stabilize is only a few tenths of a second.
      When grinding, the balancer is stable, even during substantial changes in speed.
      The technique is applicable to almost all grinding machines on the market and the
      first grinders using the technique have just been put on the market.

PMID- 8996670
TI  - Effect of contact conditions on the mechanical impedance of the finger.
AB  - The influence of physical factors on the mechanical impedance at the palmar
      surface of the finger have been investigated. The studies were conducted with 12
      subjects using random vibration over the frequency range 10 to 1000 Hz. It was
      found that increase in contact force (from 0.25 to 8 N) caused large increases in
      the modulus of the point mechanical impedance over most of the frequency range,
      increasing the area of contact with the finger (from 12.6 mm2 to 78.5 mm2)
      increased impedance at frequencies below 100 Hz and above 400 Hz. The location of
      contact with the finger also influenced the measured mechanical impedance. The
      resonance frequency increased from about 30 Hz, when vibration was applied to the
      proximal phalanx, to 600 Hz when vibration was applied to the distal phalanx. The
      addition of mass to the fingernail (0.5 to 8 g) reduced the resonance frequency
      from 700 Hz to 180 Hz and caused increased magnitudes of impedance at resonance
      by about a factor of 3. Flexing the finger affected impedance at frequencies
      between 50 and 200 Hz. The results show that the transmission of vibration to the
      fingers, and therefore the effects of vibration on the fingers, are highly
      dependent on some aspects of the contact between the fingers and the source of
      excitation. These variables are not currently quantified when assessing the
      severity of tool vibration, yet their optimisation may help to minimise some of
      the adverse effects of hand transmitted vibration.

PMID- 8996671
TI  - The influence of individual factors on the absorption of vibration energy in the
      hand and arm.
AB  - The detrimental effects of vibrating hand-held tools upon humans have been known
      for a long time, and determination of the absorption of vibration energy into the
      operator's hand and arm could be an alternative method of risk assessment. The
      energy absorption in the hand and arm during exposure to random vibration has
      been measured in 84 subjects, 40 males and 44 females. A special handle was used
      during the measurements. The influence of various experimental conditions, such
      as vibration level (3-12m/s2), vibration direction (Xh, Yh, Zh), and grip force
      (25-75 N) were studied. Furthermore, the influence on the absorption of different
      individual biological factors, such as age, weight, height, hand and arm
      dimensions as well as blood pressure were also investigated. The subject also
      provided demographic data through a questionnaire covering work, symptoms of
      finger blanching and numbness as well as current use of nicotine (snuff of
      tobacco). The results show that energy absorption is influenced by exposure
      directions and levels as well as grip forces. Furthermore, the results show that
      individual biological differences between subjects, for instance age, hand volume
      and hand thickness, have a significant influence on the amount of absorbed
      energy. Blood pressure had no influence on the absorption. The same was also
      found for the subjective reported symptoms of finger blanching or numbness as
      well as for use of nicotine.

PMID- 8996672
TI  - Derivation of mean impedance curves as a basis for mechanical models of the human
      hand-arm system.
AB  - he use of mechanical models of the human hand-arm system in test stands can
      substitute man in several activities with exposition to vibration. An example is
      prototype testing of percussion drills. Modelling should be based on ascertained
      mean impedance curves of the hand-arm system. The method chosen was deriving
      curves for the three directions by using DIN and ISO standards (such as DIN
      45677) as well as comprehensive literature and results of own measurements. At
      present it can be stated that: Literature is scarce especially with regard to the
      test conditions. Thus the causes of--sometimes largely--varying test results are
      difficult or impossible to be traced. There is conformity with the standards in
      principle. However, deviations exist for the frequency range determining the aw
      value so that the application of mean standard curves for modelling the hand-arm
      system can lead to mistakes compared to test persons. Literature clearly shows an
      influence of hand grip force on the impedance curves. Standardisation seems not
      to consider this influence sufficiently. Mechanical models should take it into
      account. For feed force, there is no evidence for such a clear influence on the
      impedance curves.

PMID- 8996673
TI  - Measurement and evaluation of coupling forces when using hand-held power tools.
AB  - Coupling forces at the interface of the hand-arm system and the vibrating tool
      have a substantial effect on the actual vibration exposure. The paper presents a
      method for the qualitative assessment of coupling forces. This method--presently
      under discussion in the form of a draft standard within DIN (1) and ISO (2)--is
      mainly based on the results of a joint research project (University of Dortmund,
      University of Mainz and BIA). The workplace-related determination of a coupling
      factor can be considered the very heart of the method. For technical reasons, the
      coupling force is split up into the gripping and the pushing force. The paper
      describes the requirements applying to the measurement and evaluation. Examples
      are given to illustrate the determination of coupling forces with a view to
      assessing vibration exposure.

PMID- 8996674
TI  - Integrated stand for vibration and ergonomic investigations of hand-held impact
      tools.
AB  - This paper presents an integrated test stand for hand-held impact tools (rnu)
      enabling complex vibration and ergonomic investigations according to the
      standards ISO 8662, EN 28662 and EU directives. The stand testing range has been
      established basing on the system investigations (1) concerning all the factors
      harmful to the operator's health existing on the work stands equipped with rnu.
      The parameters of rnu supply which should be monitored and recorded during
      investigations have been also established. Course of investigations is controlled
      by a computer provided with the original SYS-DEA program (7). The integrated
      stand is equipped with a Quality Assurance System of investigations making
      impossible measurement and recording of erroneous signals. Simultaneous
      acquisition, measurement and recording of fourteen signals are done during the
      course of investigations. This paper contains a short description of stand design
      and the results of comparative investigations conducted with use of new
      generation of pneumatic hammers as a source adapted for man-operator requirements
      (5). Comparative investigations showed that the mechanical part of the stand
      simulates dynamic conditions of a man-operator and rnu investigations without
      presence of operators are possible. Moreover, the stand makes possible very good
      repeatability of tool fastening and supplying. Vibration spectrum correlation
      coefficient for particular fastening in the stand is in the range: 0.967-0.994
      and is decidedly higher than the operator's pushing force. Vibration
      investigations revealed design drawbacks of the impact energy absorber made
      according to the standards SO 8662 and EN 28662 that should be eliminated.
      Results of the rnu investigations attained in the integrated stand make possible
      a complex evaluation of tested tools not only in the range of vibration and noise
      but also in the range of the most important ergonomic parameters connected with
      for example operator's physical overload and issue of certificates by certifying
      units.

PMID- 8996675
TI  - Development of a grip force dependent hand-arm vibration model.
AB  - The driving-point mechanical impedance of the human hand-arm system is strongly
      dependent on the grip force and excitation frequency. In this study, the
      biodynamic response of the human hand-arm is characterized by three and four
      degree-of-freedom (DOF) linear and nonlinear mass excited model incorporating
      grip force dependence of the restoring and dissipative properties. The model
      parameters are identified by minimizing a constrained objective function
      compromising impedence magnitude and phase errors between the computed and
      measured target driving-point mechanical impedance characteristics. The target
      impedance values are established in the 10 to 1000 Hz frequency range from the
      measurements performed in the three orthogonal directions (Xh, Yh and Zh) using 2
      x g peak acceleration sinusoidal excitation and different magnitudes of constant
      grip force ranging from 10 to 50 N. The linear and nonlinear models are analyzed
      to determine the driving-point mechanical impedance characteristics for different
      levels of grip force. The computed response characteristics are compared to the
      target values to demonstrate the validity of the proposed models. The results of
      the study revealed that the four-DOF nonlinear grip force dependent model yields
      good correlation with the measured response in all three directions, for the
      range of grip forces considered.

PMID- 8996677
TI  - Human response to shock-type vibration on hand.
AB  - Points of subjective equality between continuous vibration and shock-type
      vibration (repeated vibration) were examined in hand-transmitted vibration to
      find a tendency of human response to shock-type vibration (repeated vibration
      with short duration). On time and off time of the repeated vibrations were
      changed from 10 ms to 5s. Each adjustment involved a 10 second exposure to the
      repeated vibration and subsequent 10 second exposure to the continuous vibration.
      Frequencies of the vibrations were 8, 16, 31.5 and 100 Hz. Subjective magnitude
      of the shock-type vibrations (repeated vibrations) decreased with increase of off
      time and with decrease of on-time of the repeated vibrations. Results of this
      experiment were compared with calculated r.m.s. values, r.m.q. values and other
      quantity. R.m.s. values underestimated the repeated vibration and r.m.q. values
      overestimated the vibration compared with human responses.

PMID- 8996676
TI  - Exposure-response relationship for vibration-induced white finger among forestry
      workers.
AB  - The relation between the occurrence of white finger and vibration exposure was
      investigated in a group of 222 forestry workers using chain saws. The forestry
      workers and 195 controls never exposed to hand-transmitted vibration were
      interviewed by occupational health physicians. The diagnosis of vibration-induced
      white finger (VWF) was made on the basis of subjective symptoms of finger
      blanching and the results of a cold test with plethysmographic measurement of
      finger systolic blood pressure. Vibration was measured on a representative sample
      of AV and non-AV chain saws. Daily vibration exposure was assessed in terms of 8
      h energy-equivalent frequency-weighted acceleration [A(8)]. A lifetime vibration
      dose was estimated for each of the forestry workers. The overall prevalence of
      VWF among the forestry workers was 23.4%. Raynaud's phenomenon was discovered in
      2.6% of the controls. In the forestry workers, the risk of VWF showed positive
      increments with each increment of vibration dose, suggesting a monotonic dose
      response relationship. The responsiveness to cold in the digital arteries of the
      forestry workers was also found to increase with increasing vibration dose. The
      estimated relation between VWF and vibration exposure showed that the expected
      occurrence of VWF increased in approximately linear proportion to either A(8)
      (with exposure duration unchanged) or the number of years of exposure (with
      equivalent acceleration unchanged). In this study of VWF among forestry workers
      the estimated exposure-response relation showed that if the magnitude of
      vibration acceleration is doubled, the total duration of exposure should be
      halved to produce an equivalent effect. On the basis of the assessment of
      vibration exposure, the estimated risk for VWF in the study population was found
      to be lower than that predicted by the International Standard ISO 5349. The
      results of this study tend to support the vibration exposure levels currently
      under discussion within the European Union.

PMID- 8996679
TI  - European standardization in the framework of the machinery directive: aims and
      strategies.
AB  - The Machinery Directive 89/392/EEC contains the obligation to inform the user
      about the hand-arm vibration emission of hand-held and hand-guided tools and of
      steering wheals etc. at mobile equipment of the weighted acceleration value
      exceeds 2.6 m/s2. The measurements should be made under standardized working
      conditions (type testing) to obtain comparable results and to allow the user the
      selection of tools with the lowest vibration emission. The European
      Standardization Organization CEN is obliged to elaborate all necessary standards
      for type testing, which only unity realistic working conditions and exclude
      evaluation of health risks arising from the use of these tools. This approach is
      quite new and requires a great effort from the experts of the involved
      manufactures and the responsible occupational safety authorities. The
      presentation informs about the present stage of this work in the CEN Technical
      Committee 231 "Mechanical Vibration and Shock" which is responsible for the
      elaboration of the general measurement standards as a basis for the specific test
      codes from the machine groups oriented Technical Committees.

PMID- 8996678
TI  - Comparison of different methods for vibration measurements on hand-held vibrating
      tools.
AB  - Vibration measurements have been done on hand-held tools in a group of 48 platers
      by evaluating the individual vibration acceleration and absorption of vibration
      energy. The measurement of acceleration has been done frequency-weighted and
      frequency-unweighted in accordance with ISO 5349 and NIOSH (USA) recommendations
      for hand-arm vibration standards, respectively. The acceleration and the energy
      absorption have been measured simultaneously in the three orthogonal directions,
      the latter by using a specially designed adapter. The exposure time has been
      determined by both subjective rating and objective measurements. Individual
      energy-equivalent accelerations and vibration dosages have been calculated from
      these data. The outcome shows that the type of tool was critical to vibration
      load when the different measures for determining vibration levels were used. Of
      the methods used, the evaluation specified by ISO 5349 makes most consideration
      of low frequencies of vibration (< 50 Hz), absorption of vibration energy middle
      frequencies (50-200 Hz) and NIOSH of high frequencies (> 200 Hz). The results
      show a poor correlation between the three methods used. Close agreement between
      mean subjective rating and objective measurement of the average exposure time was
      found. Further studies of the relation between results presented here and
      generated disturbance will be conducted, which may clarify any exposure-response
      relationship.

PMID- 8996680
TI  - Augmented response in plasma atrial natriuretic peptide to dynamic exercise in
      patients with congestive heart failure.
AB  - Neurohormonal activation is present and neurohormonal responses to dynamic
      exercise are altered in patients with congestive heart failure (CHF). The aim of
      this study was to determine if the responses of atrial natriuretic peptide (ANP)
      normalized for peak oxygen consumption (peak VO2) to exercise are augmented in
      patients with CHF. Ventilatory and ANP responses were assessed in 28 patients
      with CHF (NYHA classes II: 16, III: 12), 17 patients in NYHA class I, and 14
      normal subjects during symptom-limited cardiopulmonary exercise testing. Plasma
      ANP was measured at rest and immediately after peak exercise. The increase in ANP
      was divided by peak VO2 and this ratio [ANP-Exercise Ratio: (peak ANP-rest
      ANP)/peak VO2] was compared among the 3 groups. Peak VO2 (Normal, NYHA I, CHF:
      29.9 +/- 1.7, 24.0 +/- 1.3, 17.4 +/- 0.8 ml/min per kg), anaerobic threshold and
      peak work rate were lower in patients with CHF. The resting ANP level was
      significantly higher in patients with CHF (Normal, NYHA I, CHF: 35.4 +/- 4.6,
      42.9 +/- 5.8, 80.8 +/- 12.9 pg/ml). The ANP level increased during exercise in
      all 3 groups, and patients with CHF had a significantly higher ANP level than
      normal subjects and NYHA class I patients (Normal, NYHA I, CHF: 65.3 +/- 10.7,
      75.9 +/- 14.4, 141.6 +/- 20.1 pg/ml). The ANP-Exercise Ratio in patients with CHF
      was significantly higher than those in normal subjects and NYHA class I patients
      (Normal, NYHA I, CHF: 0.96 +/- 0.26, 1.32 +/- 0.38, 3.59 +/- 0.72). These data
      suggest that patients with CHF but not those in NYHA class I have an augmented
      ANP response, as reflected by both absolute ANP levels and by the exercise ratio,
      which was normalized by the peak exercise level.

PMID- 8996681
TI  - Assessment of regional early diastolic function using cine magnetic resonance
      imaging in patients with hypertrophic cardiomyopathy.
AB  - In patients with hypertrophic cardiomyopathy (HCM), we conducted cine magnetic
      resonance imaging (MRI) studies in which our objectives were to quantify the
      regional early diastolic function of the left ventricle and to evaluate the
      relationship between regional diastolic function and hypertrophy. Short-axis
      images of the left ventricle were recorded by cine MRI in 8 control patients and
      24 patients with HCM. The images were then divided into 10 blocks to evaluate
      regional early diastolic function. The regional wall-thickness-time curve, the
      radius-time curve, and their first-derivative curves were computed for each of
      the 10 blocks. There was no difference between the time-to-peak-radius-increasing
      ratio and the time-to-peak-wall-thickness-thinning ratio in the 10 blocks in the
      control patients. These 2 parameters in the patients with HCM were significantly
      longer than those in the control patients. There was also a significant linear
      correlation between the time-to-peak-wall-thickness-thinning ratio and regional
      wall thickness. Cine MRI was useful for evaluating regional early diastolic
      function, which is apparently related to regional hypertrophy, in patients with
      HCM.

PMID- 8996682
TI  - Decreased heart rate variability in patients with diabetes mellitus and ischemic
      heart disease.
AB  - We investigated the characteristics of decreased heart rate variability (HRV) in
      diabetic patients with ischemic heart disease (IHD). Twenty-one healthy control
      subjects, 17 diabetic patients without IHD, and 33 diabetic patients with IHD
      were studied. The diabetic patients with IHD were subdivided into 2 groups
      according to the severity of their IHD: severe or mild. HRV was evaluated in all
      subjects using the spectral variables of the all-frequency, low-frequency, high
      frequency (AF, LF, HF) components and the LF/HF ratio were determined from Holter
      recordings. The AF and LF components in patients with diabetes only or diabetes
      and severe IHD were significantly lower than in control group, but the HF
      component was significantly lower only in the group of patients with diabetes and
      severe IHD. The LF/HF ratio did not differ significantly among the 4 groups, but
      was the lowest in diabetic patients without IHD. Patients with diabetes and mild
      IHD showed a slight decrease in HRV, but this was not significant. With regard to
      the circadian rhythm of HRV, the AF and LF components in patients with diabetes
      only or diabetes and severe IHD were significantly decreased and showed the same
      pattern throughout the day. However, the HF component was decreased during more
      time zones in patients with diabetes and severe IHD, whereas the LF/HF ratio was
      lower during more time zones in the diabetes-only group. All spectral variables
      showed a tendency to be inversely related to the duration of diabetes in all
      diabetic patients. In particular, the LF/HF ratio showed a significant negative
      correlation. The HRV of diabetic patients was characterized by a decreased LF/HF
      ratio. It was concluded that, although HRV in diabetic patients with severe IHD
      was reduced mainly as a result of diabetic neuropathy, this was also partly due
      to a decline in parasympathetic tone as a result of myocardial injury.

PMID- 8996683
TI  - Relationship between bronchial hyperreactivity and symptoms of cardiac asthma in
      patients with non-valvular left ventricular failure.
AB  - To determine whether a relationship exists between bronchial hyperreactivity and
      cardiac asthma, which is commonly observed in patients with left heart failure, a
      methacholine inhalation test was performed in 15 patients with stable left
      ventricular failure (LVF) and 10 normal subjects. The subjects were divided into
      3 groups based on symptoms of nocturnal coughing and/or wheezing in acute
      exacerbation of LVF. Group A consisted of 8 patients with nocturnal coughing
      and/or wheezing. Group B consisted of 7 patients without such symptoms, and Group
      C consisted of the 10 age-matched normal controls. Eleven of the 15 patients with
      LVF showed a significant increase in respiratory resistance in the methacholine
      inhalation test, as opposed to none of the normal subjects. The median cumulative
      dose which produced a 35% decrease in respiratory conductance (PD35Grs) was
      significantly lower in Group A than in Group B (1.45 log units and 1.90 log
      units, respectively, p < 0.05). The results of pulmonary function tests were not
      significantly different between Groups A and B. The minimum cumulative dose
      required to initiate a decrease in respiratory conductance from the baseline, as
      an index of bronchial sensitivity to methacholine, was significantly correlated
      with DLCO/VA (r = 0.710, p < 0.01). We conclude that bronchial hyperreactivity is
      responsible for cardiac asthma and that it might be related to pulmonary
      interstitial changes in stable patients with non-valvular LVF.

PMID- 8996684
TI  - Long-term outcome of percutaneous transluminal coronary angioplasty and coronary
      bypass surgery for multivessel coronary artery disease.
AB  - We studied the short- and long-term outcomes of 97 patients treated with
      percutaneous transluminal coronary angioplasty (PTCA) and 72 patients treated
      with coronary artery bypass graft surgery (CABG) for multivessel coronary artery
      disease in a single hospital in 1989. Patients treated with CABG had a higher
      angina class, a higher incidence of diabetes mellitus and a greater extent of the
      disease. Complete revascularization was achieved in 61 patients (85%) with CABG
      and in 45 patients (46%) with PTCA (p < 0.001). Initial success of PTCA and CABG
      was obtained in 95% and 94% of the patients with PTCA and CABG, respectively.
      Actuarial survival rates at 5 years were similar (96% in the PTCA group; 94% in
      the CABG group). Fewer patients suffered from cardiac death or myocardial
      infarction in the CABG group than in the PTCA group, but this difference was not
      significant. The rate of survival free from death, myocardial infarction, CABG
      and repeat PTCA, was significantly higher in the CABG group than in the PTCA
      group (85% vs 48%; p < 0.001). These results suggest that CABG provides a
      favorable long-term outcome in patients with multivessel coronary artery disease
      and that PTCA provides a similar outcome in these patients when applied to
      suitable lesions, although more patients who undergo PTCA require repeat
      procedures.

PMID- 8996685
TI  - Activity immediately before the onset of non-fatal myocardial infarction and
      sudden cardiac death.
AB  - To investigate triggers for the occurrence of acute myocardial infarction (AMI)
      and sudden cardiac death (SCD), we examined the activities immediately before the
      time of onset in 149 cases of non-fatal AMI and 110 cases of SCD. All of the
      cases in which death occurred within 24 h from the onset of the underlying cause
      were considered SCD as long as the cause of death was of cardiac origin or
      unknown. We calculated the average time which is spent on each activity in the
      life cycle of Japanese people and estimated the number of incidence of each
      activity assuming a uniform distribution. Estimated values and actual values were
      compared. The results were as follows: 1) The incidence of non-fatal AMI and SCD
      was low while sleeping or resting or doing light work, and was high while using
      the toilet or doing sport or heavy work. 2) the incidence of SCD was also high
      even during moderate exertion, such as taking a bath or, walking or cycling, and
      it was significantly higher than that in the group of non-fatal AMI. 3) The
      incidence of non-fatal AMI was high while eating or drinking. 4) Many of the
      patients with SCD had past histories of circulatory diseases, compared to those
      with non-fatal AMI. This difference in past histories may account for the high
      incidence of SCD during moderate exertion.

PMID- 8996686
TI  - Advantages and disadvantages of dobutamine stress echocardiography compared with
      treadmill exercise electrocardiography in detecting ischemia.
AB  - We compared the effectiveness and practicability of dobutamine stress
      echocardiography (DSE) and treadmill exercise electrocardiographic testing (TMT)
      for detecting coronary artery disease. Ninety-six patients (mean age 58.8 +/- 9.0
      years) who presented for coronary angiography underwent both DSE and symptom
      limited TMT. Two-dimensional echocardiography was performed to detect ischemia
      induced wall motion abnormalities during incremental dobutamine infusion (5-40
      micrograms/kg per min administered in 5 min steps). The sensitivity of detecting
      ischemia was 63% for TMT and 79% for DSE (p < 0.05); the specificity was 61% for
      TMT and 88% for DSE (p < 0.05). The accuracy of TMT was 63% and of DSE 82% (p <
      0.01). In patients in whom both tests gave true-positive results, the maximum ST
      depression was evaluated during DSE and TMT (n = 31). The ST segment depressions
      detected by DSE were significantly smaller than those detected by TMT (0.04 +/-
      0.04 mV vs 0.17 +/- 0.07 mV, p < 0.01), and 10 patients had no evidence of ST
      segment depression despite the presence of new wall motion abnormalities. DSE
      took significantly longer to perform than TMT (26.0 +/- 5.0 min vs 5.5 +/- 2.0
      min, p < 0.01). Thus, DSE is more sensitive, specific and accurate than TMT in
      detecting coronary artery disease and can detect ischemia at an earlier stage.
      However, it takes longer to perform than TMT and thus may be less suitable for
      routine clinical use.

PMID- 8996687
TI  - Effect of acetylsalicylic acid on metabolism and contractility in the ischemic
      reperfused heart.
AB  - The effect of acetylsalicylic acid (ASA) on high-energy phosphates (adenosine
      triphosphate: ATP, creatine phosphate: CrP, inorganic phosphate: Pi) and
      intracellular pH during myocardial ischemia and reperfusion was studied using
      phosphorus 31-nuclear magnetic resonance (31P-NMR) in the isolated rabbit hearts.
      Coronary flow, left ventricular systolic developed pressure (LV Dev.P) and left
      ventricular end-diastolic pressure (LVEDP) were also measured. Langendorff hearts
      perfused at 37 degrees C with the perfluorochemical emulsion Fluosol-43 were
      subjected to 15 min and 30 min of zero-flow ischemia and to 15 min of low-flow
      ischemia (coronary perfusion pressure = 20 mmHg) followed by 65 min of
      reperfusion (control, Group I). ASA (0.28 mmol/L) was infused either for the
      entire experimental period from beginning 45 min prior to ischemia (Group II) and
      infused immediately after reperfusion (Group III). During ischemia, Group II
      showed a significant suppression of the decrease in the ATP level and pH with
      both zero-flow and low-flow ischemia compared to those in the other groups, and
      moreover the increase in Pi and the decrease in CrP in low-flow ischemia were
      also suppressed. In Group III, the ATP level during reperfusion was significantly
      higher than that in Group I, but was not significantly different from that in 30
      min zero-flow ischemia. In 30 min zero-flow ischemia, Pi, CrP and coronary flow
      after reperfusion in Group II tended to recover to preischemic values. There were
      no differences in LV Dev.P among the 3 groups. In conclusion, ASA has a
      protective effect on myocardial high-energy phosphates during ischemia and
      reperfusion in rabbit hearts.

PMID- 8996688
TI  - Cardiac angiotensin converting enzyme and endothelin receptor in rats with
      chronic myocardial infarction.
AB  - To ascertain the pathophysiological roles of the renin-angiotensin system and
      endothelin in heart failure and cardiac hypertrophy, we assessed changes in
      cardiac angiotensin converting enzyme (ACE) and endothelin-1 (ET-1) receptor
      using rats in which myocardial infarction was induced by left coronary ligation.
      The animals were decapitated 1 or 8 months after the operation. Cardiac ACE and
      ET-1 receptor were quantified by computerized in vitro autoradiography using 125I
      MK351A (a lisinopril derivative) and 125I-ET-1. One month after myocardial
      infarction, cardiac weight and plasma atrial natriuretic peptide had increased in
      rats with infarction, compared to sham-operated controls, indicating the presence
      of chronic left ventricular dysfunction, although exchangeable body sodium and
      plasma renin activity were unchanged. Cardiac ACE increased markedly in the
      infarcted area and moderately in hypertrophied myocardium without any change in
      affinity compared to sham-operated rats. On the other hand, there was no change
      in cardiac ET-1 receptors in infarcted rats. The same results were found even at
      8 months after myocardial infarction. The present study indicates that cardiac
      ACE may participate in tissue repair at the site of myocardial infarction and may
      also play a role in the pathophysiology of cardiac hypertrophy in rats with
      chronic heart failure. However, the present results do not reveal whether ET-1
      receptor participates in the pathophysiology of cardiac hypertrophy in this
      model.

PMID- 8996689
TI  - Local delivery of antithrombotic drug prevents restenosis after balloon
      angioplasty in atherosclerotic rabbit artery.
AB  - We investigated the ability of various antithrombotic drugs, delivered locally,
      to prevent restenosis after angioplasty in hypercholesterolemic rabbits. After
      dilating atherosclerotic iliac stenoses by balloon angioplasty, a low dose of
      heparin or a new antithrombotic drug, such as low molecular weight heparin
      (fragmin), argatroban, or batroxobin, was delivered locally using the balloon
      double-occlusion technique. In 1 group, high-dose heparin was administered
      intravenously. Animals that received no drugs served as a control group. After
      angioplasty, the stenotic segment was dilated and the mean percentage luminal
      stenosis fell from 89% to 9% in the group that received locally delivered
      heparin, from 88% to 7% in the group that received locally delivered argatroban,
      from 87% to 11% in the group that received locally delivered fragmin, from 88% to
      15% in the group that received locally delivered batroxobin, from 82% to 18% in
      the group that received i.v. heparin (p < 0.0001 compared with before angioplasty
      in each case), and from 84% to 17% in the control group (p < 0.005 compared with
      before angioplasty). Twenty-eight days after angioplasty, the percentage luminal
      stenosis remained at 14% in the group that received locally delivered argatroban,
      15% in the group that received locally delivered fragmin, and 28% in the group
      that received locally delivered batroxobin, whereas it increased to 45% in the
      group that received i.v. heparin, 30% in the group that received locally
      delivered heparin and 72% in the control group (p < 0.05 compared with after
      angioplasty in each case). Thus, local delivery low doses of new antithrombotic
      drugs prevents restenosis after angioplasty without affecting systemic
      coagulability; heparin, whether administered locally or intravenously, was less
      effective than the new drugs in preventing restenosis.

PMID- 8996690
TI  - Chaotic musical murmur in aortic regurgitation.
AB  - We report an interesting case of aortic regurgitation. Phonocardiographically,
      the shape of the diastolic musical murmur in this case changed in each cardiac
      cycle despite being in sinus rhythm, in the same posture and in the same
      breathing phase. Experimentally, we were able to obtain a similar noise pattern
      using an artificial respirator and a hemispherical silicone membrane. We
      concluded that the irregular and chaotic change in the shape of the diastolic
      musical murmur in the present case occurred due to irregular swaying of the non
      coronary cusp under the influence of the Venturi effect owing to a regurgitant
      jet stream.

PMID- 8996691
TI  - Diastolic plateau wave of pulmonary artery pressure in severe congestive heart
      failure.
AB  - We describe 3 cases of severe congestive heart failure. The patients exhibited a
      marked decrease in transmitral flow velocity during atrial contraction and an
      abnormal diastolic plateau wave of pulmonary artery pressure (PAP). The first
      patient was a 60-year-old man with acute myocardial infarction and acute renal
      failure in whom pulmonary capillary wedge pressure (PCWP) was raised to 20 mmHg.
      Pulsed Doppler echocardiography revealed a marked decrease in transmitral flow
      velocity during atrial contraction, and the PAP waveform showed a mid to late
      diastolic plateau wave. Treatment for congestive heart failure reduced PCWP to 10
      mmHg and the PAP waveform returned to normal. Doppler examination revealed the
      normal transmitral flow velocity pattern. The second patient was a 37-year-old
      woman with subarachnoid hemorrhage and the third patient a 74-year-old man with
      acute myocardial infarction. In these patients, the PAP waveform also showed a
      diastolic plateau wave, which was abolished by treatment. We believe that the
      diastolic plateau wave of PAP indicates left ventricular diastolic dysfunction
      and marked elevation of left ventricular filling pressure.

PMID- 8996692
TI  - Structural characterization and hydrolytic degradation of a Zn metal initiated
      copolymer of L-lactide and epsilon-caprolactone.
AB  - A bioresorbable aliphatic polyester was synthesized by bulk copolymerization of a
      1/1 M/M L,L-lactide/epsilon-caprolactone mixture using zinc metal as initiator.
      The actual composition of the copolymer was found to be 1.5/1 as deduced from 1H
      NMR spectra obtained in DMSO-d6 solutions where higher resolution was obtained as
      compared with chlorinated solvents. Resonances due to L-lactyl units (L)
      exhibited triads stereosensitivity, epsilon-oxycaproyl units (C) being sensitive
      to dyads. Average lengths of both poly(lactic acid) and polycaprolactone
      sequences were evaluated and showed the presence of rather long PLA blocks.
      Furthermore, no CLC triad signal was found, suggesting the absence of
      transesterification rearrangements. 10 x 10 x 2 mm specimens made of the
      copolymer were allowed to age in isoosmolar pH = 7.4 phosphate buffer at 37
      degrees C. Degradation was monitored by various analytical techniques such as
      SEC, X-ray diffractometry, DSC, and 1H NMR. Data were compared with the behaviour
      of PCL and PLA homopolymers allowed to age under similar conditions.
      Crystallinity and composition changes are discussed in terms of preferential
      degradation in L- and C-containing amorphous domains, crystallized long PLA
      blocks being much more resistant.

PMID- 8996693
TI  - Changes in binding affinity of a monoclonal antibody to a platelet binding domain
      of fibrinogen adsorbed to biomaterials.
AB  - Previously, we found that when fibrinogen-coated polyurethanes resided in a
      buffer for a period of time (the 'residence time') platelet adhesion to these
      materials decreased. Other changes in adsorbed fibrinogen such as decreases in
      polyclonal antibody binding and SDS elutability supported the conclusion that
      fibrinogen undergoes postadsorptive conformational changes. Subsequently we
      measured the binding of monoclonal antibodies to the three putative platelet
      binding sites on fibrinogen, using a single mid-range concentration of antibody.
      We found that binding of a monoclonal antibody to the platelet binding site at
      the C-terminus of the gamma chain of fibrinogen changed little with residence
      time, while binding of monoclonal antibodies to the other two putative binding
      sites on fibrinogen either increased with residence time (RGDF at A alpha 95-98),
      or first increased and then decreased with residence time (RGDS at A alpha 572
      575). In the current study, we measured antibody binding affinity, Ka, by
      measuring antibody binding at a series of antibody concentrations. This is a more
      sensitive method for detecting changes in adsorbed fibrinogen than measuring
      antibody binding from a single antibody concentration. The Ka was determined for
      two antibodies, M1 (4A5), which binds to a platelet binding domain of fibrinogen
      (gamma 402-411) and R1 (155 B 1616), which binds to residues 87-100 of the A
      alpha chain (containing an RGDF site). A summary of the results for the M1
      antibody are as follows. The Ka was higher for M1 binding to fibrinogen adsorbed
      to Immulon I than to Biomer, Biospan or poly(ethylene terephthalate), suggesting
      that fibrinogen adsorbed to Immulon I is more platelet adhesive than fibrinogen
      adsorbed to the other polymers. On Biospan, the Ka decreased from 2.8 x 10(9) to
      1.0 x 10(9) M-1 after a 24 h 37 degrees C residence time, which correlated with
      the decrease in platelet adhesiveness of adsorbed fibrinogen observed previously
      under these conditions. The change in Ka was greater when adsorbed fibrinogen was
      kept under denaturing conditions. For example, the Ka decreased from 2.8 x 10(9)
      to 0.8 x 10(9) M-1 after a 1 h 70 degrees C residence time whereas it remained
      approximately the same, 2.9 x 10(9) M-1, after a 24 h 0 degree C residence time.

PMID- 8996694
TI  - Improved blood compatibility of drawn polyamide sheets.
AB  - A series of aliphatic polyamide (nylon) sheets with different draw ratios were
      prepared and their blood-contacting properties examined in relation to the bulk
      and surface characteristics. Increases in both the molecular orientation and
      crystallinity were observed with increasing draw ratio. Their surface wettability
      slightly decreased with draw ratio, indicating less amide linkages at their
      surfaces by the drawing process. An increase in contact angle hysteresis by the
      drawing process is thought to be due to the existence of more amorphous chains at
      the surfaces. The adsorption of albumin and fibrinogen onto nylon sheets was
      significantly reduced with draw ratio, suggesting the formation of well
      established crystalline-amorphous microdomain structures at the surfaces. Blood
      compatibility of these surfaces was greatly improved with draw ratio in terms of
      a change in cytoplasmic calcium levels in platelets contacting these surfaces.
      Thus, it is suggested that the control of crystalline-amorphous microdomain
      structures by the drawing process is a feasible approach to improve blood
      compatibility of commercially available semicrystalline polyamides.

PMID- 8996695
TI  - An immuno-isolative membrane capable of consuming cytolytic complement proteins.
AB  - In an earlier article we demonstrated that xenogeneic islets of Langerhans in an
      agarose/poly(styrenesulfonic acid) (PSSa) microcapsule were protected from the
      host's immune rejection and that diabetic animals maintained a normal glucose
      level for a long period of time after their transplantation. In this study, we
      attempted to make clear the immuno-isolative mechanisms of the agarose-PSSa
      microcapsule from the standpoint of permeability of antibodies and complement
      proteins through this microcapsule membrane. It was found that the microcapsule
      was unable to prevent the permeation of IgG for longer than a few days, but
      protect the encapsulated cells from cytolytic complement attack. This strongly
      suggests that the cytolytic complement activity was lost during permeation
      through the microcapsule, probably because of the strong interaction of PSSa in
      the membrane with complement proteins. Based on these findings we proposed the
      minimum requirement for the immuno-isolative membrane to be applicable to
      xenotransplantation.

PMID- 8996696
TI  - Gender determination of the Linne's two-toed sloth (Choloepus didactylus) using
      SRY amplified from hair.
AB  - Polymerase chain reaction (PCR) amplification of a partial fragment of the sex
      determining region Y (SRY) gene was used for sexing a young Linne's two-toed
      sloth (Choloepus didactylus), a species in which gender determination from the
      external genitalia is difficult. DNA was extracted from hairs of a 5-month-old
      sloth as well as the dam and sire as external controls. A SRY fragment (216
      bases) was PCR-amplified both from the offspring and the sire, but not amplified
      from the dam. The DNA sequence (166 bases without primers) of the sloth PCR
      product was determined and compared with SRY sequences of other mammals
      previously reported. High homology of their nucleotide (74.1-86.8%) and deduced
      amino acid (63.6-85.5%) sequences indicates that the PCR product of the sloth was
      amplified from a region of the SRY gene, and that SRY sequences are conserved
      throughout mammalian orders. From the result the sex of the young sloth was
      determined as a male. The PCR method using hairs for sexing the sloth provides an
      advantageous tool for captive propagation plan in zoos. To the authors'
      knowledge, no report regarding SRY sequences in the order Xenarthra (Edentata)
      has been published.

PMID- 8996697
TI  - Hormonal regulation of T-cell subsets in the oviduct: an immunohistochemical
      study using sex-hormone-treated chicken.
AB  - The present immunohistochemical study deals with dynamic alteration of T-cell
      subsets in the oviduct sex-hormone-treated chickens. Monoclonal antibodies (CT3,
      CT4, and CT8) specific for the chicken homologues of CD3, CD4, and CD8 were used
      in estrogen- or progesterone-treated chickens. In control animals, no lymphocytes
      appeared throughout the oviduct until 4 weeks of age. When 7-day-old chickens
      were injected with either diethylstilbestrol (DES) or (DES) plus progesterone, T
      cells immunoreactive for CT3 first infiltrated the oviduct at 12 hr after the
      hormone treatment. Their frequency of occurrence rose from 48 to 96 hr.
      Subsequently, CT3+ cells in the magnum declined in number per area coincident
      with the proliferation of albuminous glands in the lamina propria, while in the
      vagina no decline of T cells was observed. The population of T-cell subsets in
      the lamina propria of both the magnum and vagina was significantly higher in the
      DES-treated chickens than in DES plus progesterone-treated chickens. Among T-cell
      subsets CT8+ cells were more numerous than CT4+ cells throughout the study, this
      relative frequency being shared by normal adults. Depopulation of lymphocytes
      from the thymus, spleen and cecal tonsil, their mobilization to the circulating
      blood, and subsequent dynamic infiltration into the oviduct suggested that the
      sex hormones induced the traffic of T cells from the lymphoid organs into the
      oviduct.

PMID- 8996699
TI  - Infectivity and persistence of Salmonella typhimurium for bengalees, a variety of
      Lonchura striata, using an isolate from a bengalee.
AB  - Due to its importance in public health, Salmonella Typhimurium originating from a
      naturally infected bengalee (Lonchura striata), a common cage bird, was examined
      for its infectivity and persistence for the same species. Eight birds per group
      for each experiment were used. When bengalees were inoculated orally with 10(2),
      10(4) or 10(5) colony forming units (CFU) of S. Typhimurium and observed for 7
      days, all the birds receiving 10(5) CFU were positive for the organism in the
      liver, spleen or the intestines, and necrotic foci in the liver were observed in
      6 birds. When bengalees were inoculated with 10(5) CFU of S. Typhimurium and
      observed for 22 days, the organism was found in fecal samples throughout the
      experimental period and the maximum S. Typhimurium counts in feces were 3.9 x
      10(8) CFU per gram. S. Typhimurium was recovered from the liver, spleen and
      intestines in 7 birds and necrotic foci in the liver were also observed in 7
      birds. The results indicate that S. Typhimurium originating from a naturally
      infected bengalee is pathogenic to these birds and the persistence of the
      pathogen lasts at least for 22 days.

PMID- 8996698
TI  - The proto-oncogene c-myb is expressed in sporadic bovine lymphoma, but not in
      enzootic bovine leukosis.
AB  - We examined bovine c-myb gene expression in six samples of sporadic bovine
      lymphomas (two calf, three thymic and one intermediate) and five of enzootic
      bovine leukosis. Tumor cells of the sporadic bovine lymphomas were of immature
      cell lineage (one B lymphoma and five T lymphomas). The c-myb mRNA was expressed
      in almost all the sporadic bovine lymphomas (except for one thymic form)
      including a BoCD8 single positive T lymphoma. On the contrary, c-myb was not
      expressed in mature B lymphomas of enzootic bovine leukosis. The results suggest
      that c-myb expression is closely associated with tumor cell differentiation of
      bovine lymphomas.

PMID- 8996700
TI  - Incidence of diarrhea with antibiotics and the increase of clostridia in rabbits.
AB  - Rabbits were treated with a single intravenous injection of various antibiotics.
      More than 40 per cent of the animals showed diarrhea after being treated with
      sulbactam/cefoperazone, cefmetazole, clindamycin, piperacillin or aspoxicillin.
      Clostridium difficile was isolated from sulbactam/cefoperazone-treated diarrheic
      rabbits, with their cecal contents showing positive reaction in a latex
      agglutination test for C. difficile enterotoxin. However, 27 cefmetazole-induced
      diarrheic cases were not associated with C. difficile. Other enteropathogenic
      bacteria, such as Campylobacter spp., Bacillus cereus, enteropathogenic
      Escherichia coli, coagulase positive Staphylococcus aureus, Salmonella spp.,
      Vibrio spp., Clostridium perfringens and Clostridium spiroforme, were not
      isolated from either of diarrheic rabbit. However, the counts of clostridia
      remarkably increased in the intestine of cefmetazole-associated diarrheic
      rabbits. This was ascribed to the overgrowth of Clostridium innocuum and
      Clostridium sporogenes. There were no remarkable differences in changes in other
      bacterial population between diarrheic and non-diarrheic rabbits.

PMID- 8996701
TI  - Mineral metabolism in plasma, urine and bone of periparturient cows fed anionic
      diets with different calcium and phosphorous contents.
AB  - The objective of this experiment was to evaluate the influences of Ca and P
      contents in an anionic diet on the mineral metabolism in plasma, urine and bone
      in periparturient diary cows. Fifteen multiparous Holstein-Friesian cows were
      divided into 3 dietary groups (5 cows/group) by dietary Ca and P contents and
      dietary cation-anion balance [(Na + K) - (Cl + S) mEq/kg DM]; diet 1 [low Ca
      (0.46%), low P (0.24%), cationic (+195.8 mEq/kg DM)]; diet 2 [low Ca (0.46%), low
      P (0.24%), anionic (-32.4 mEq/kg DM)]; and diet 3 [high Ca (0.93%), high P
      (0.60%), anionic (-41.0 mEq/kg DM)]. Cows were fed one of these 3 diets from
      approximately 4 weeks before the expected calving date to 5 days after calving.
      There was no outbreak of milk fever in any cows fed these 3 diets; however,
      plasma Ca levels at 1 and 2 days after calving tended to be higher in the cows
      fed diet 3 than those in the cows fed diets 1 or 2. Fractional urinary excretion
      of Ca in the cows fed diet 2 or 3 was higher than that in the cows fed diet 1.
      Fractional urinary excretion and plasma level of Pi were higher during the
      periparturient period in the cows fed diet 3 than those in the cows fed diets 1
      or 2. There were no significant differences in plasma parathyroid hormone levels
      among the 3 groups. In the spongy substance of ilium at 5 days after calving, the
      Ca and Mg contents bone volume and trabecular thickness were the lowest, but not
      significant, in the cows fed diet 2. These data suggest that sufficient Ca and P
      contents in an anionic diet may be effective in maintaining plasma Ca and Pi
      levels of periparturient cows and further in preventing of potential bone damage
      brought about by increased urinary mineral excretion following the feeding of an
      anionic diet.

PMID- 8996703
TI  - Measurement of extravascular lung water by the double indicator dilution method
      using heat and sodium in horses under general anesthesia.
AB  - Rapid infusion is believed to be harmful to the lung, however, the pathological
      status of pulmonary edema resulting from excessive fluid therapy in horses has
      not been clarified because the quantitative diagnosis of pulmonary edema is
      impossible. To evaluate the precision of the double indicator dilution method
      using heat and sodium in horses, which allows the quantitative diagnosis of
      pulmonary edema, we compared extravascular lung water volume measured using a
      lung water computer based on the theory of the double indicator dilution method
      with that determined by the direct method. The value of extravascular thermal
      volume (ETV) determined by the double indicator dilution method was 7.82 +/- 0.62
      ml/kg and the detection ratio of ETV to the value of pulmonary extravascular
      water volume (PEWV) by the direct method was 0.996 +/- 0.038. There was a
      significant correlation between ETV and PEWV (P < 0.05), and the regression line
      was Y = 1.23 X - 1.73 with a correlation coefficient of 0.953. The value of
      extravascular lung water determined by the double indicator dilution method was
      significantly consistent with that obtained by the direct method, indicating the
      high precision of the double indicator dilution method in normal horse lungs.

PMID- 8996702
TI  - Equine synovial villi: distinctive structural organization of vasculature and
      novel nerve endings.
AB  - The structural arrangement and cellular distribution of endothelial and lining
      cells of the synovial villi were studied in the equine palmar/plantar recess of
      the metacarpo- and metatarsophalangeal joints by light microscopy and electron
      microscopy. The extent and distribution of blood vessels varied with villous
      shape and length. The majority of vessels formed concentric circles in cross and
      longitudinal sections and probably are arranged in a convoluted, spiral or
      helical pattern. The villi do not contain smooth muscle cells or typical
      capillaries as observed in other organs. Under the electron microscope, the
      endothelium is surrounded by connective tissue and discontinuous circular cells,
      presumably fibroblasts. The outermost layer was sometimes surrounded by type A
      and/or B synovial cells. The lumen of the blood vessels at the top of villus
      appeared to be constricted in most cases, with a diameter of about 12 +/- 3
      microns. Blood vessels formed by more than six endothelial cells in the middle
      portion of villus generally were not constricted. Well-developed cytoplasmic
      processes extended into the lumen of blood vessels. The constriction of blood
      vessels with no apparent smooth muscle presence and the observation of numerous
      intermediate filaments in the cytoplasm of the endothelial cells suggests that
      these villous blood vessels constrict through contraction of their own
      endothelial cells. Lining cells were distributed unevenly even within a single
      villus; the villous lining cells seemed to have directional preferences with
      domination of synovial type A cells. Surprisingly, structures resembling
      myelinated nerve ends (approximately 0.2 microns) were observed between
      juxtaposed endothelial cells as well as directly on an endothelial cell,
      suggesting that these nerve endings may be a sensor detector of either pressure
      or temperature or have a proprioceptive-like function. Synovial villi have a
      distinctive structural arrangement of vessels, lining cells, and nerve endings.

PMID- 8996704
TI  - Immunohistochemically-determined changes in the distribution of insulin-like
      growth factor-I (IGF-I) and epidermal growth factor (EGF) in the bovine
      endometrium during the estrous cycle.
AB  - The aims of this study were to investigate whether there are cell-specific
      distributions of insulin-like growth factor I (IGF-I) and epidermal growth factor
      (EGF) in the endometrium, and to determine whether or not the expression of these
      factors varies with the stage of the estrous cycle. Fifty-four endometrial biopsy
      specimens were collected from normal cycle Holstein-Friesian heifers. The
      endometrial specimens were divided into nine groups (at least five different
      animals per group) corresponding to the following days of the cycle: days 20-0, 1
      3, 4-5, 6-7, 8-10, 11-13, 14-15, 16-17, and 18-19 (day 0 = estrus). IGF-I and EGF
      were localized by immunohistochemistry in the intact heifer endometrium
      throughout the estrous cycle. Throughout the estrous cycle, IGF-I was localized
      in the luminal epithelium and stroma with a little staining in the glandular
      epithelium (P < 0.01). In the luminal epithelium, the number of IGF-I-positive
      cells increased on days 1-3, 6-7, 11-13, and 16-17. In the stroma, the number of
      IGF-I-positive cells increased on days 8-10 and 20-3. The number of positively
      stained cells in the glandular epithelium increased around the estrous period.
      EGF stained intensely in the stroma but very little in the luminal and glandular
      epithelia (P < 0.01). In the stroma, three peaks in the number of EGF-positive
      cells were observed: on days 1-3, 6-7, and 11-13. These results demonstrate
      cyclical changes in the endometrial cell types localization of IGF-I and EGF.

PMID- 8996705
TI  - Demonstration of rat CAR bacillus using a labelled streptavidin biotin (LSAB)
      method.
AB  - Immunohistochemical detection of rat CAR bacillus antigen in paraffin-embedded
      experimentally infected rat lungs, using an immunoperoxidase technique based on
      the labelled streptavidin biotin (LSAB) method and 3-amino-9-ethylcarbazole (AEC)
      as substrate is described in this paper. The pattern of immunostaining was
      confined to the ciliated bronchial epithelium and the specificity of this
      technique was confirmed. The use of AEC as substrate was evaluated more efficient
      than diaminobenzidine (DAB). The usefulness of this immunoperoxidase technique
      for the detection of CAR bacillus in rats and its advantages compared to the
      indirect immunofluorescence (IF) are discussed.

PMID- 8996706
TI  - A new host record of Camelostrongylus mentulatus (Nematoda; Trichostrongyloidea)
      from abomasum of a giraffe at a zoo in Japan.
AB  - Camelostrongylus mentulatus (Railliet et Henry, 1909) Orloff, 1933 (Nematoda;
      Trichostrongyloidea) was found from the abomasum of a three-year-old female cape
      giraffe, Giraffa camelopardalis giraffa, born and died in a zoo park in Yamaguchi
      prefecture, Japan. This is the new host record from Giraffidae and geographical
      distribution of C. mentulatus. Present case of C. mentulatus might be infected
      from other ruminants, e.g., camels, antelopes and goats, kept at a same paddock
      in the zoo. Risk of imported parasitic diseases by the zoo animals from outside
      of Japan is discussed.

PMID- 8996708
TI  - An immunohistochemical analysis of T-cell subsets in the chicken bursa of
      Fabricius during postnatal stages of development.
AB  - T-cell subsets in the chicken bursa of Fabricius were analysed
      immunohistochemically during postnatal stages. Distinct types of T cells were
      present both in the surface epithelium and lamina propria of the bursa. TcR1+ and
      CT8+ cells were predominant in the surface epithelium, while TcR2+ and CT8+ cells
      were numerous in the lamina propria. These T-cell subsets peaked in frequency of
      occurrence at 5 weeks. They then decreased in number, and a few T cells remained
      in the bursa until 15 weeks of age. This result showed that the bursa of chickens
      is furnished with the distinct types of T-cell subsets at early postnatal stages
      of development to maintain its local immunity.

PMID- 8996707
TI  - Monoclonal antibody against bovine Lactoferricin and its epitopic site.
AB  - Bovine lactoferricin (LFcin B) is a strong antimicrobial peptide derived from N
      lobe of lactoferrin. To study the immunochemical and structural properties of
      LFcin B, monoclonal antibody (mAb) was prepared and the amino acid sequence
      concerning with the binding to mAb has been identified. Mice injected with LFcin
      B showed no production of antibody specific to this peptide, whereas those with
      LFcin B-KLH conjugate produced anti-LFcin B antibodies. None of the mAb reacted
      with bovine lactoferrin C-lobe, human lactoferrin or LFcin H. By the reactivity
      of the mAb against the peptides synthesized on cellulose membranes using SPOTs
      and against chemically modified derivatives of LFcin B, the antigenic determinant
      of LFcin B was identified to be the sequence of "QWR".

PMID- 8996709
TI  - Time course of ethylene thiourea in maternal plasma, amniotic fluid and embryos
      in rats following single oral dosing.
AB  - Ethylene thiourea (ETU) was administered once orally to pregnant rats on
      gestation day 12 at a dose of 200 mg/kg, and its concentration-time courses in
      the maternal plasma, amniotic fluid and embryos were investigated. The ETU
      concentrations in the maternal plasma and amniotic fluid reached the peak level
      about 2 hr after dosing, then declined gradually and had disappeared by 48 hr. In
      embryos, the concentration of ETU peaked at 30 min after dosing and disappeared
      at 48 hr. The prolonged exposure of the embryos to the high concentration of ETU
      in the amniotic fluid could be partially responsible for the teratogenic effect
      of ETU.

PMID- 8996710
TI  - Effects of cryopreservation of DNA synthesis in the inner cell mass of in vitro
      matured/in vitro fertilized bovine embryos frozen in various cryoprotectants.
AB  - The rate of DNA synthesis in the inner cell mass (ICM) of frozen-thawed bovine
      embryos was examined. Bovine blastocysts derived from in vitro matured/in vitro
      fertilized oocytes were frozen with 1.8 M ethylene glycol (EG), 1.6 M propylene
      glycol (PG) and 1.4 M glycerol plus 0.25 M sucrose (GL). Viable embryos, after
      thawing and culture beyond the blastocysts stage, were examined by
      immunocytochemical staining for detection of DNA synthesis by ICM cells. The
      numbers of bromodeoxyuridine-immunoreactive ICM cells of frozen-thawed embryos
      prepared with EG (10.7) and GL (11.5) were significantly lower than those of
      unfrozen embryos (17.3). The results suggest that the rates of proliferation of
      ICM cells of frozen-thawed bovine embryos tend to be lower than those of unfrozen
      embryos irrespective of the cryoprotectant used.

PMID- 8996711
TI  - Psychological stress, neuroimmunomodulation, and susceptibility to infectious
      diseases in animals and man: a review.
AB  - This article reviews research on the role of psychological stress, personality,
      social support and other psychosocial factors in bacterial, viral and parasitic
      infections. After 100 years of research on man and animals, psychological stress
      is considered as a potential cofactor in the pathogenesis of infectious disease.
      Psychological stress seems able to alter the susceptibility of animals and man to
      infectious agents, influencing the onset, course and outcome of certain
      infectious pathologies. Many experiments have identified in neuroimmunomodulation
      the principal mediator of the alterations associated with conditions of stress.
      The development of psychoneuroimmunology has fostered in-depth study of the
      complex relationship between psychosocial factors, the central nervous system,
      the immune system and infectious disease. Although antimicrobial drugs have
      certainly remained the basis of all anti-infective therapy, this type of study
      has already led some authors to propose and experiment protocols of psychological
      intervention or psychoimmunotherapy in pathologies such as tuberculosis, or
      herpes simplex virus or human immunodeficiency virus infections. The
      psychoneuroimmunological approach to infectious diseases will probably grow in
      importance in the future not only in the setting of research in psychosomatic
      medicine but also in that of clinical microbiology.

PMID- 8996712
TI  - Study and course of the psychological profile in 77 patients expressing panic
      disorder with agoraphobia after cognitive behaviour therapy with or without
      buspirone.
AB  - BACKGROUND: The change of psychopathological dimensions during treatment of panic
      disorder is attracting increasing interest. METHODS: A population of subjects
      experiencing panic disorder with agoraphobia is evaluated with the French version
      of the factor structure of the Symptom Checklist 90 R (SCL 90 R). Two groups of
      patients are compared: a group receiving cognitive behaviour therapy (CBT)
      combined with buspirone and a group receiving cognitive behaviour therapy
      combined with placebo. RESULTS: Comparative analysis of pre- and post-test
      changes between both groups completing treatment showed that the combination
      cognitive behaviour therapy plus buspirone provided better results than those in
      patients who had received cognitive behaviour therapy plus placebo. This
      difference between treatments did not persist at the 1-year follow-up, since,
      while results had been effectively maintained in the CBT plus buspirone group,
      the CBT plus placebo group continued to improve significantly for the target
      dimensions of treatment. CONCLUSIONS: Psychopathological dimensions on the SCL 90
      R show that combination of buspirone and cognitive behaviour therapy accelerates
      the behaviour modification process only in the short term.

PMID- 8996713
TI  - The relationship of menstrual cycle and pregnancy to compulsive hairpulling.
AB  - BACKGROUND: Trichotillomania (TTM) or compulsive hairpulling is a cyclical
      disorder that presents predominantly in females. Anecdotal reports of symptom
      worsening in the premenstruum and during pregnancy led us to retrospectively
      study the role of these events in hairpulling behavior. METHODS: Questionnaires
      assessing demographics, current hairpulling behavior, and the reported effects of
      menstruation and pregnancy on urges, actual hairpulling and behavioral control
      were administered to clinic patients and volunteers at a hairpulling conference.
      The MGH Hairpulling Scale, Beck Depression Inventory and Beck Anxiety Inventory
      were also completed. Data from 59 hairpullers were analyzed. RESULTS:
      Premenstrual symptom exacerbation was reported for actual hairpulling urge
      intensity and frequency, and ability to control pulling and was alleviated during
      menstruation and shortly thereafter. The impact of pregnancy was less
      unidirectional, with both symptom exacerbation and lessening reported.
      CONCLUSIONS: The menstrual cycle appears to affect compulsive hairpulling and
      deserves recognition in both the assessment and treatment of this disorder. The
      impact of pregnancy on TTM is less clear.

PMID- 8996714
TI  - The diagnosis of major depression in end-stage renal disease.
AB  - BACKGROUND: Although major depression commonly occurs in medically ill patients,
      it can be difficult to diagnose since depression and many medical illnesses share
      common physical symptoms. METHODS: This study was designed to evaluate patients
      with end-stage renal disease (ESRD) for major depressive disorder using three
      diagnostic approaches, to assess the Beck Depression Inventory as a screening
      instrument for major depression, and to examine the association of anhedonia with
      a diagnosis of major depression in ESRD patients who deny depressed mood.
      RESULTS: Rates of major depression varied from 6 to 34% according to the criteria
      that were used. The sensitivity of the Beck Depression Inventory was found to be
      modest. Anhedonia was a helpful clue for diagnosing depression in patients who
      denied depressed mood. CONCLUSIONS: The findings illustrate the current
      difficulties in applying DSM criteria for major depression to medical patients
      and underscore the need for more specific guidelines.

PMID- 8996716
TI  - Lucid dreaming as a treatment for recurrent nightmares.
AB  - BACKGROUND: Lucid dreams occur when a person becomes aware that he or she is
      dreaming while still in the dream state. Previous reports on the use of lucid
      dreaming in the treatment of nightmares do not contain adequate baseline data,
      follow-up data, or both. METHODS: A treatment of recurrent nightmares
      incorporating progressive muscle relaxation, guided imagery, and lucid dream
      induction is presented for 2 case studies. Three other cases were treated with
      lucid dream induction alone. The duration of the nightmares ranged from once
      every few days to once every few months. RESULTS: The procedures were effective
      in all 5 cases. A 1-year follow-up showed that 4 of the subjects no longer had
      nightmares and that 1 subject experienced a decrease in the intensity and
      frequency of her nightmares. CONCLUSIONS: The alleviation of recurrent nightmares
      in these 5 cases parallels the results reported by other authors who have used
      training in lucid dreaming to treat nightmares. Our results support the idea that
      treatments based on lucid dream induction can be of therapeutic value. Based on
      these and other case studies, it remains unclear whether the principal factor
      responsible for the alleviation of nightmares is lucidity itself, or the ability
      to alter some aspect of the dream.

PMID- 8996715
TI  - The effect of behavioral intervention on the psychological distress of Holocaust
      survivors with cancer.
AB  - METHODS: This study describes a particular psychological intervention offered to
      a unique self-selected population of cancer patients who, 50 years earlier, had
      experienced the extreme trauma of the Holocaust. A total of 45 patients in follow
      up at the Outpatient Clinic of the Oncology Department at the Hadassah University
      Hospital were approached. Two self-reports were administered: the Brief Symptom
      Inventory to assess psychological distress, and the Impact of Events Scale to
      assess intrusion and avoidance. RESULTS: There was a significant decrease in
      distress by the specific short-term psychological intervention used in this
      traumatized population. However, 3 months later the improvement virtually
      disappeared. CONCLUSION: This study failed to demonstrate a long-lasting effect
      of behavioral intervention upon Holocaust survivors with cancer.

PMID- 8996718
TI  - Application of the Gen-Probe amplified MTD test (Mycobacterium tuberculosis
      Direct Test) in the diagnostics of tuberculosis.
AB  - A commercially available set, the Gen-Probe amplified MTD test (Mycobacterium
      tuberculosis Direct Test; Gen-Probe Incorporated, 9080 Campus Point Drive, 92121
      California, USA) has been applied for the detection of the M. tuberculosis
      complex in clinical material in parallel to direct microscopy and cultivation in
      liquid and solid growth media. The method is based on the amplification of a
      specific 16 S rRNA segment. Detection of the amplified segment is facilitated by
      single-strand probes tagged with acridinium ester. Hybridization results are
      interpreted in RLU (Relative Light Unit) values and readings exceeding 30,000 RLU
      are considered positive, lower values being negative. In all, there have examined
      69 samples of clinical material (35 sputums, 29 bronchoalveolar washings or
      bronchial aspirations, and 5 cerebrospinal fluids). As positive amplification
      controls served freshly cultured strains of M. tuberculosis and M. bovis BCG;
      negative controls were M. gordonae, M. xenopi, M. kansasii, and M. terrae. Out of
      a total 69 samples examined, M. tuberculosis was detected in 28 (40.7%) cases by
      the Gen-Probe amplified MTD test, in 10 (14.5%) cases by direct microscopy, and
      in 26 (37.7%) cases by cultivation. In samples from 8 patients M. tuberculosis
      was detected by just Gen-Probe amplified MTD test the results of cultivation and
      direct microscopy being negative. Culture-positive samples yielded no Gen-Probe
      amplified MTD test negative results. The Gen-Probe amplified MTD test contributes
      significantly to the speeding up of diagnostics in tuberculosis because the
      results is obtainable with six hours. Under the conditions of this pilot study
      the results were termed as preliminary and collaborating physicians were advised
      to wait for cultivation results and their definite evaluation.

PMID- 8996717
TI  - Hepatitis A vaccination by Havrix in the Czech U.N. Troops according to data of
      seroprevalence in 1991-1995.
AB  - Viral hepatitis A is a common disease, particularly in developing countries. All
      staff and troops of the U.N. (United Nations) are vaccinated by the Havrix
      vaccine. Till 1995 we did not vaccinate Czech troops which have operated in the
      area of former Yugoslavia. The main goal of this study was to obtain data about
      the seroprevalence of hepatitis A antibody among the Czech U.N. troops before
      their departure to the conflict area and to optimize the vaccination approach.
      The serum samples were examined by the MEIA (Microparticle Enzyme Immunoassay)
      method in the fully automated system for immunoassays IMx in the Military
      Institute of Health in Ceske Budejovice. We used HAVAB kits of Abbott Company.
      692 serum samples (military staff of the Czech U.N. troops in Yugoslavia) were
      examined in 1991-1995. In the laboratory 19 samples were eliminated due to small
      amounts (less than 50 microliters) or haemolysis. 673 (1991 - 65, 1992 - 296,
      1993 - 265, 1994 - 35, 1995 - 12) were investigated. The staff was divided into
      four age cohorts by decades (20-29, 30-39, 40-49, 50-59); 26.0%, 47.4%, 24.9% and
      1.7%, respectively. There were 253 (37.4%) positive samples and 420 (62.6%)
      negatives ones, ratio 1:1.7. The ratio of the positive and negative samples-
      immunity rate and seroprevalence--were 1:0.4 (26.2%), 1:0.6 (37.9%); 1:0.9
      (46.4%) and 1:2.7 (72.7%), respectively in the age cohorts. The results show a
      relatively low seroprevalence of the anti-HAV antibody in all the age cohorts and
      necessity to vaccinate the Czech U.N. troops by the special basic schedule-
      Havrix 2 x 720 E.U. at the same time. This regimen will be used in the new units
      that will be stationed in Bosnia. So far 200 persons have been vaccinated in this
      way.

PMID- 8996719
TI  - Prevalence of Trichomonas vaginalis in prostitutes in Turkey.
AB  - Prostitutes are an important group for the transmission of a number of sexually
      transmitted diseases (STD) all over the world. Infection with T. vaginalis is one
      of the most common. In this study, the incidence and diagnostic procedures for
      Trichomonas vaginalis infection as one of the sexually transmitted diseases
      (STD's) have been studied. In legal prostitutes in Ankara, Turkey, 64 (25%) of
      225 vaginal wet smears were positive for T. vaginalis. There was no significant
      difference between the detection rates of direct phase-contrast microscopy and
      culture for the identification of T. vaginalis.

PMID- 8996721
TI  - Comparison of concentration of Cu and Zn in children population.
AB  - The biological monitoring of essential metals in blood, urine and hair became
      important for the control of biological processes and for the study of the
      influence of environmental conditions on the human organism. To determine the
      normal level of copper and zinc in the children population group of Central
      Bohemia (Benesov), 98 samples of whole blood, 133 samples of urine and 135
      samples of hair have been analysed by means of atomic absorption spectroscopy.
      The mineralisation of blood and hair samples in the microwave oven and 3-fold
      dilution of urine were used for the sample preparation. Arithmetic and geometric
      means as well as median and ratio Zn/Cu were calculated. The concentration of the
      elements under study in all samples did not differ from the values published in
      the literature. Some differences between girls and boys have been found.

PMID- 8996720
TI  - Differentiation of Proteus mirabilis and Proteus vulgaris strains by means of
      proticine typing: a longitudinal epidemiological study.
AB  - In the years 1979, 1980, 1982-83, 1986-87 and 1992-93, 673 strains of P.
      mirabilis and 25 strains of P. vulgaris were isolated from the urinary tracts of
      patients at a Teaching Hospital in Brno. In 1982-83 and 1992-93, strains of P.
      mirabilis and P. vulgaris were isolated from the urine and faeces of two groups
      of Brno population and used as controls. Using the P/S typing method, 94.7% of
      hospital isolates and 85.5% of control strains could be differentiated by their
      types. The strains that could not be typed (8.2%) were classified as PO/SO or N
      types; in the remaining strains, 182 various P/S types could be distinguished.
      The strains that could not be typed occurred more frequently in control groups
      (48 out of 337) than in hospital isolates (37 out of 698). Over the whole period,
      P5/S6, S7, S9 and P1/S2, S11 were the prevailing P/S types of hospital isolates
      and were placed, together with related types, in groups P5 and P1, respectively.
      In 1982-83, a significant shift (p < 0.01) from the initially prevailing P5/S6,
      S7, S9 type to the P1/S2, S11 type of P. mirabilis was recorded. Approximately
      one third of the hospital isolates in all the periods examined was found to be
      sporadic, with the exception of 1992-93 when the sporadic strains doubled in
      frequency (p < 0.01). In control strains, the frequency of sporadic types was
      twice that of the hospital isolates (p < 0.01) in 1982-83 and, 1992-93, it was
      equal to the frequency of hospital isolates. This implied a fall in the presence
      of hospital-acquired strains in the last period of study.

PMID- 8996722
TI  - Breast cancer epidemiology in Czech Republic.
AB  - Breast cancer is the most commonly diagnosed cancer and a leading cause of
      malignant neoplasms death in Czech female population. Only about half of all new
      breast cancer cases are diagnosed in early stage, consequently therapeutically
      and prognostically favourable. The benefit of conceptual breast cancer screening,
      showing an absolute decrease in mortality, can be expected after 5-7 years of
      screening. That is why early start of mammography hand in hand with clinical
      examination of the breast will have to be one of the highest priority in the
      national health promotion programmes.

PMID- 8996723
TI  - Concentrations of polychlorinated biphenyls and chlorinated pesticides in human
      breast milk--a case study.
AB  - Concentrations of chlorinated pesticides (p,p'-DDE, lindane), hexachlorobenzene
      (HCB), sum of polychlorinated biphenyls (PCBs), and PCB congeners in breast milk
      during lactation and the distribution of the chlorinated compounds in fat tissue,
      blood serum and breast milk were pursued in five primi- or secundipara from the
      hinterland of a clinic of gynaecology and obstetrics in Brno in 1993. Capillary
      gas chromatography with ECD detection was used for the determination of the
      residues. The concentrations of HCB, lindane, p,p'-DDe, and sum of PCBs ranged
      from 42.5 to 238.4, from < 1.0 to 7.4 from 231.4 to 557.6, and from 661.3 to
      2888.9 micrograms.kg-1 of milk fat, respectively. Seventeen PCB congeners were
      screened, of which 11 were identified in most of the milk samples (IUPAC numbers
      28, 101, 118, 126, 128, 138, 153, 156, 170, 180, 194). Congeners 138, 153, 170,
      and 180 were the most abundant and their concentrations in microgram.kg-1 of milk
      fat ranged from 122.9 to 501.0 for 153, from 103.4 to 372.1 for 138, from 66.1 to
      407.9 for 180, from 26.8 to 183.1 for 170, and from 10.0 to 41.7 for 118.

PMID- 8996724
TI  - Interaction of styrene and ethylmethylketone in the induction of cytochrome P450
      enzymes in rat lung, kidney and liver after separate and combined inhalation
      exposures.
AB  - The present study compares the induction of different cytochrome P450 forms
      (CYP1A1/2, 2B1, 2E1) after pretreatment with styrene, ethylmethylketone
      separately or in combined exposures. Combined exposures lead to cumulative
      elevation of CYP levels, except for CYP1A1 and 2B1. Induction of CYP1A1 was
      higher in liver and kidney respectively and did not change significantly with the
      pretreatment mode. Styrene produced two times higher induction of CYP1A2 in the
      lung and kidney than ethylmethylketone. The simultaneous application of both
      inducers lead to significantly higher induction of CYP1A2 than that estimated
      after pretreatment with each of the inducers separately. CYP2B1 was induced by
      styrene to higher extent in the liver, where it was almost indetectable in
      controls. Major form of cytochrome P450 induced by styrene proved to be CYP2E1-
      about 3-fold induction of chlorzoxazone hydroxylation activity in the liver and
      2.5 times in the lung. Ethylmethylketone significantly potentiated the CYP2E1
      induction ability of styrene. This induction of CYP2E1-dependent catalytic
      activity correlates with the enzyme levels detected by immunoblotting.

PMID- 8996725
TI  - Effects of acetone on the capacity of o-xylene and toluene to induce several
      forms of cytochrome P450 in rat liver.
AB  - The influence of acetone on the induction of P450 in lung, kidney and liver by
      toluene and xylene was studied in an attempt to estimate more precisely the range
      of P450 which are proposed to function in the activation of xylenes and toluene
      metabolites in the conditions of combined exposures. The addition of acetone
      potentiated the induction of CYP1A1/2 to 4 minutes ethoxyresorufin deethylation
      that from control animals after pretreatment with toluene. The level of this
      enzymatic activity (0.4 nmol/min/mgP) estimated in this study is consistent with
      the turnover number of the purified CYP1A1 (0.45 nmol/min/mgP). The assay
      activity results were confirmed by immunoblotting detection of the CYP1A1/2
      levels. Oppositely, the addition of acetone in the inhalation protocol using o
      xylene lead to a lower ethoxyresorufin deethylation activity as that in rat
      livers from rats pretreated with xylene alone. Pentoxyresorufin deethylation
      activity was enhanced strongly by toluene (3.5 times the controls) and by xylene
      (4 times the controls) and the addition of acetone potentiated the induction of
      CYP2B1 both after xylene and toluene. A 4 fold induction of CYP2E1 dependent
      chlorzoxazone hydroxylation after exposure to toluene and 2.5 fold after xylene
      corresponded to the enzyme levels of P45020E1 detected by immunoblotting. The
      addition of acetone consequently potentiated the induction effect of toluene and
      xylene and increased its levels more markedly in the case of xylene, which is a
      weaker inducer of CYP2E1.

PMID- 8996726
TI  - The role of the National Institute of Public Health in the field of infections
      with natural focality.
AB  - In the post-war period the National Institute of Public Health, later Institutes
      of Epidemiology and Microbiology, headed by K. Raska, ranked among famous
      laboratories in the world due to its priority findings and original results.
      Research results of the Institute stimulated further research not only in
      Czechoslovakia but also abroad, in laboratories of Europe and America. The
      authors emphasize the significance of certain results in the epidemiology and
      ecology of infections characterized by natural focality. In the first place they
      discuss the isolation of TBE in 1948 and 1949 by Gallia et al., and the study of
      the role of birds and bats as hosts of TBE. Significant for the recognition of
      zoonotic influenza viruses are papers by Tumova, and as regards rabies in rodents
      the studies of Sodja et al. The institute paid attention to the introduction of
      Coxiella burnetii into the north-west of Bohemia. The institute's activities in
      the study of tularaemia, leptospirosis, Lyme borreliosis, and toxoplasmosis are
      also described. Raska's concept of epidemiological surveillance in the prevention
      of zoonoses with natural focality was fully enforced by workers of the institute.
      Many results of the Institute have been adopted by the WHO; it was demonstrated
      that it is possible by appropriate methods not only to detect human diseases in
      places where they are known but also to discover them in nature extensively
      altered by man.

PMID- 8996727
TI  - Prevention of hand-arm vibration hazards: from laboratory to practice.
AB  - Many studies were made throughout the world regarding the medical and technical
      aspects of hand-arm vibration since the first description by Loriga in 1911 of
      the vibration syndrome. Despite that the protection of operators against
      vibration hazards had progressed very slowly in practice with one notable
      exception, the case of chain saw users for whom several countries developed a
      comprehensive programme to eradicate the diseases successfully; regulations,
      antivibration tools, medical screening, preventive treatment. If all these
      actions are not carried out simultaneously in an industrial sector the
      transmission of knowledge from the laboratory to practice may be a failure or
      very costly in money, time and energy, as this article will show it in the case
      of suspended rammers and breakers.

PMID- 8996728
TI  - Raynaud's phenomenon in different groups of workers using hand-held vibrating
      tools.
AB  - The dose-effect relationship showed in the Annex A of the ISO standard 5349-1986
      can be used for preventing vibration-induced white fingers (VWF) because it
      allows to calculate the latent period for the lowest risk of VWF. The aim of this
      study was to assess the risk of VWF in three different occupational groups of
      workers whose members operated the same vibrating power tools and the same
      industrial processes throughout the workday. Each occupational group was employed
      in two foundries and they were considered to be very stable with a low turnover
      rate. The mean frequency-weighted acceleration magnitudes measured from pneumatic
      rammers (25.3 +/- 3.3 ms-2) where three times higher than from chipping hammers
      (8.4 +/- 3.8 ms-2) and six times higher than from grinders (3.8 +/- 1.1 ms-2).
      Medical examinations were carried out in 102 men consisting of 22 chippers, 42
      rammers and 38 grinders. The results of this study showed that the relationship
      between lifetime exposure to hand-arm vibration and the vascular disorders can be
      predicted quite well using the Annex A of ISO standard only in one occupational
      group, that is, in chippers. Thirty-six percent of chippers reported blanching
      symptoms, but only five percent of the rammers and three percent of the grinders
      had these vascular disturbances. Our results may be explained by the fact that
      vibration received by an operator depends on the manner in which the tool is
      used. In a foundry three following work processes are performed: preparing forms
      in ramming mix, cleaning and grinding of castings during which different forces
      are used by operators. It seems very likely that the energy absorbtion in the
      hands and arms of chippers must be stronger than in other studied groups.

PMID- 8996729
TI  - Vibration exposure dose dependency of clinical stage, examination results and
      symptoms in vibration syndrome.
AB  - The vibration exposure dose dependency of clinical stage, examination results and
      symptoms are valuable for evaluation of exposure effect in vibration syndrome.
      The 1973 national survey of 461 chain saw operators in private forests was
      reexamined with respect to vibration exposure dose (VD) and clinical stage
      (Stockholm Workshop scales: CIRP-0 to 3 and SN-0 to 3 stages). VD was calculated
      by the formula "ahw(eq.4h) x D (days) x Y (years)". Vibration exposure dose index
      (VDI) was calculated according to the VD level. Subjects were divided into five
      VDI, four CIRP stage and four SN stage groups, respectively. Ratio of four CIRP
      and SN in VDI, examination results and prevalences of symptoms were compared
      between VDI-1 and the other VDI groups. Vibration dose dependency was observed in
      Stockholm Workshop scales (CIRP and SN stage) and examination results (prevalence
      of CIRP, vibrotactile perception threshold, prevalence of numbness in hands, and
      fingertip pinch strength). Higher VDI (VDI-5) was associated with higher
      prevalence of hypersensitivity to cold, muscle weakness and deterioration of
      finger function. Which formula is more useful to evaluate cumulative vibration
      effects is still controversial.

PMID- 8996730
TI  - Evaluation of the white finger risk prediction model in ISO 5349 suggests need
      for prospective studies.
AB  - The risk prediction model for white fingers in Annex A of ISO 5349 is not likely
      to offer protection from all tools and all work processes. It is also probable
      that some work place changes it has initiated are either redundant or lack the
      intended effect. The main reasons for these shortcomings are the following. The
      often demonstrated disagreement between predicted and observed white fingers
      occurrence may be related to the fact that the model is based on latency data.
      This leads to an overestimation, to an unknown extent, of true group risks. A
      possible healthy worker effect, resulting in underestimation, has not been
      considered, and uncertainty because of recall bias is connected with using
      latency as effect variable in a slowly developing disorder like white fingers.
      The diagnostic criteria for white fingers have varied over the years, causing a
      possible inclusion of circulatory disturbances other than those induced by
      vibration. Among insufficiently clarified matters unrelated to vibration are
      variations in individual susceptibility and other host factors that modify
      vibration effects, uncertainty concerning daily or total effective exposure, and
      the fact that variation in work methods and processes as well as ergonomic
      factors other than vibration tend to make different groups incomparable form the
      viewpoint of risk of injury. Lack of sufficient data on vibration measurements
      and employment durations add to the uncertainty, as do variations in tool
      conditions (grinder wheels, etc) and inherent difficulties in measurement.
      Finally, the ISO 5349 frequency-weighting curve only relates to acute sensory
      effects rather than chronic effects on vascular functions like white fingers, and
      directional difference in sensitivity has not been incorporated in the curve.
      Data on exposure-response relationships are needed from prospective studies that
      monitor the dose of exposure to special vibration types and all relevant
      environmental agents, employ diagnostics with good sensitivity, specificity and
      predictive value, and pay attention to environmental or individual confounding
      factors and effect modifiers. Before such data are available, the ISO 5349 model
      should not be used for risk prediction. It can serve, however, as an incentive
      for manufacturers to produce tools that vibrate less, and for employers to
      implement practical measures in order to reduce the total and dose of effective
      exposure.

PMID- 8996731
TI  - Application of a new technology to the design of effective anti-vibration gloves.
AB  - Gloves that attenuate vibration above approximately 25 Hz and that exceed the
      characteristics of standard viscoelastic gloves have been developed using an air
      bladder system in the palm and fingers of a glove. Testing was performed on a
      variety of viscoelastic gloves currently marketed to obtain the ratio of energy
      leaving the handle of a vibrating device and the energy entering the hand.
      Several simple rectangular air bladders of varying thickness were developed and
      tested for their vibration attenuating characteristics. A four degree-of-freedom,
      lumped-parameter model of the vibration response of the human and air bladder was
      developed using measured hand and bladder parameters. This model, along with
      subjective criteria, was used to design and fabricate two prototype air bladder
      gloves. These gloves were tested and found to exceed adopted standard
      requirements and the characteristics of standard viscoelastic gloves. The
      prototypes in this study will be further developed, adapted and marketed for
      practical applications.

PMID- 8996732
TI  - A new examination system using photoplethysmography to evaluate skin blood flow
      during exposure to vibration.
AB  - We introduce a new examination method developed at the University Dermatology
      Hospital in Tubingen in cooperation with the Institute for High Frequency
      Techniques of Aachen Technical College and the Metabo Factory in Nurtingen,
      Germany. The Tubingen workplace simulator for studying vibration white finger
      (VWF) syndrome standardized vibrations reproducing the vibration pattern of
      actual hand-held tools. This stimulator makes it possible to evaluate on-line the
      effects of defined vibrations on skin blood flow in the fingers and to
      investigate the etiopathogenesis of vibration white finger syndrome. The
      vibration simulator itself is modelled after an altered router with two side
      mounted handles. The electronic speed control and exchangeable unbalance pins
      make it possible to adjust the frequency and amplitude of the vibrations to
      simulate actual conditions in the job. New developed photoplethysmographic
      sensors are fastened to the fingertips with double adhesive rings and measure
      blood flow in the skin. Measurements are recorded simultaneously with a multi
      channel plotter. This method is not only useful as a diagnostic tool but has
      potential future applications in pre-employment screening in the affected
      industries and in the development of reduced-vibration tools.

PMID- 8996733
TI  - Conference on the occasion of the National Institute of Public Health in Prague
      jubilee.

PMID- 8996735
TI  - In vitro activity of sparfloxacin against Salmonella typhi.
AB  - Comparative in vitro activity of sparfloxacin was determined by the broth
      dilution method against 104 clinical isolates of Salmonella typhi. All of the
      isolates were inhibited by < or = 0.12 mg/l of this fluoroquinolone. Its
      inhibitory activity was slightly superior or comparable to that of other
      fluoroquinolones tested, namely ciprofloxain and norfloxain, and significantly
      greater than the conventional drugs, such as amikacin, ampicillin, Augmentin,
      ceftazidime, clindamycin, tetracycline and trimethoprim-sulfamethoxazole, used in
      the treatment of typhoid fever.

PMID- 8996734
TI  - Antibacterial activity of TOC-50, a new parenteral cephalosporin against
      penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae.
AB  - TOC-50, a new parenteral cephalosporin, was assessed for antibacterial activity
      in vitro and in vivo. In vitro, the activity of TOC-50 was greater than
      ampicillin, erythromycin and gentamycin, and was equal to that of imipenem. The
      MICs of TOC-50 for 90% of the clinical isolates tested (MIC90 values) were 0.0125
      microgram/ml for penicillin-susceptible Streptococcus pneumoniae, 0.2
      microgram/ml for intermediately penicillin-resistant S. pneumoniae, and 0.39
      microgram/ml for fully penicillin-resistant S. pneumoniae. In murine systemic
      infection models, TOC-50 had a potent protective activity against penicillin
      susceptible of fully penicillin-resistant S. pneumoniae. Its protective activity
      was stronger than that of imipenem.

PMID- 8996736
TI  - Comparative susceptibility of clinical group A, B, C, F, and G beta-hemolytic
      streptococcal isolates to 24 antimicrobial drugs.
AB  - A total of 312 clinical beta-hemolytic streptococcal isolates (Streptococcus
      pyogenes, group A = 63; Streptococcus agalactiae, group B = 145; group C = 50;
      group F = 27; group G = 27) were examined for susceptibility to 23 and 24
      antimicrobial drugs with the Bauer-Kirby agar disk diffusion and the agar
      dilution method, respectively. Sheep blood Mueller-Hinton agar served as the
      reference medium. Wilkins-Chalgren agar supported optimal growth of group A and
      B, but not of all group C, F, and G streptococci. The group A streptococci were
      susceptible to all beta-lactam antibiotics, clindamycin, chloramphenicol,
      rifampin, teicoplanin, and vancomycin, but resistant to cotrimoxazole, fusidic
      acid, and, except for 2 strains, to fosfomycin. Resistance (R)/intermediate
      susceptibility (I) rates (R/I%) to ciprofloxacin (0/2%), ofloxacin (1/2%),
      erythromycin (1.6/0%), and clarithromycin (0/1%) were low. Higher resistance
      rates were noted with tetracyclines (doxycycline 23.8/15.9%; tetracycline
      39.7/3.2%). Among the group B streptococcal isolates, one strain was resistant
      against oxacillin and of intermediate susceptibility to penicillin G and
      cefoxitin. All isolates were susceptible to teicoplanin and rifampin. Conversely,
      all group B isolates were resistant to cotrimoxazole and fusidic acid; 69% and
      51% of these isolates were susceptible to fosfomycin and rifampin, respectively.
      R/I rates of the group B streptococcal isolates were low for ciprofloxacin and
      ofloxacin (0/0.7%), clindamycin (0.7/0%), erythromycin (1.4/ 3.5%),
      clarithromycin (1.4/0%), and chloramphenicol (0.7/0%). Resistance to
      tetracyclines was significant (doxycycline: 72.4/2.1%; tetracycline; 74.5/1.4%).
      Among the non-A, non-B beta-hemolytic streptococci, 2 group C strains were
      resistant to oxacillin and showed intermediate susceptibility to penicillin G.
      All isolates were susceptible to third and fourth-generation cephalosporins,
      imipenem, chloramphenicol, rifampin, teicoplanin, and vancomycin. R/I rates to
      the other antimicrobial drugs were: ciprofloxacin (3.9/1.9%), ofloxacin
      (2.9/1.9%), clindamycin (2.9/1%), erythromycin (5.8/0%), clarithromycin
      (3.8/2.9%), and cotrimoxazole (16.4/3.9%). Resistance against tetracyclines was
      more frequent (doxycycline: 18.3/2.9%; tetracycline: 20.2/6.7%). On the basis of
      various minor discrepancies between MIC and disk diffusion test results, it is
      proposed that the current NCCLS inhibition zone (diameter, mm) criteria
      indicative of intermediate susceptibility of beta-hemolytic streptococci be
      changed for the following antimicrobial drugs: ampicillin: 22-27 mm (only for
      group A and B beta-hemolytic streptococci); ciprofloxacin: 16-18 mm; clindamycin:
      15-18 mm; doxycycline: 17-19 mm; tetracycline: 17-19 mm, and erythromycin: 14-19
      mm.

PMID- 8996737
TI  - Antibacterial activity of cefpodoxime in vitro.
AB  - Cefpodoxime proxetil is a new orally administered prodrug which is absorbed and
      de-esterified by the intestinal mucosa to release the third-generation
      cephalosporin, cefpodoxime, and which is undergoing in vitro and in vivo
      evaluations. Using the standard agar dilution method, we compared the in vitro
      activity of this drug with other oral cephalosporins and quinolones against 637
      recent clinical isolates from Kaohsiung Veterans General Hospital in Taiwan.
      Against Escherichia coli and Klebsiella pneumoniae, cefpodoxime showed excellent
      activity, inhibiting over 90% of these isolates at 1 mg/l. Like other oral drugs
      of its class, it had little activity against Pseudomonas aeruginosa and
      Acinetobacter spp. Against Haemophilus influenzae, irrespective of beta-lactamase
      production, its activity was similar to comparative drugs. Against methicillin
      susceptible Staphylococcus aureus, cefpodoxime showed moderate activity,
      inhibiting 90% of these isolates at 4 mg/l, whereas it was inactive against
      methicillin-resistant S. aureus. However, all cephalosporins have shown little in
      vivo activity against methicillin-resistant S. aureus regardless of in vitro
      results. Cefpodoxime was inactive against Enterococcus spp. Against other
      streptococci, its activity was similar to other oral cephalosporins and
      quinolones tested. The results of this in vitro study indicated that oral
      administration of cefpodoxime should be an ideal agent in the empirical
      outpatient treatment for community-acquired cutaneous, respiratory and urinary
      tract infections.

PMID- 8996738
TI  - Susceptibility of Pseudomonas aeruginosa isolates to ceftazidime is unrelated to
      the expression of the outer membrane protein OprC.
AB  - Previously, it has been postulated that the porin OprC facilitates the diffusion
      of ceftazidime through the outer membrane of Pseudomonas aeruginosa. To further
      investigate this claim, the outer membrane protein (OMP) profiles of 22
      ceftazidime-susceptible clinical isolates were analyzed. No correlation was found
      between MIC values and the level of expression of OprC. Further, OprC was either
      undetectable or expressed in reduced amounts in 12 isolates. In contrast, OprF
      and OprE were present in all isolates studied. This study suggests that OprC is
      dispensable for the permeation of ceftazidime through the outer membrane of P.
      aeruginosa.

PMID- 8996739
TI  - 15-Deoxyspergualin, an immunosuppressive agent, used in organ transplantation
      showed suppressive effects on malarial parasites.
AB  - Deoxyspergualin (DSG), which was discovered to be an immunosuppressive agent, was
      examined for its in vivo effect on parasites of rodent malaria. Although the mice
      that were not treated by DSG had an increased parasite percentage (% parasitemia)
      until they died, those that were treated with DSG had a decreased parasitemia and
      finally had 0% parasites. The spleens of infected mice became small by DSG
      treatment. Parasitemia of mice increased again after DSG treatment was stopped.
      However, DSG was a polyamine inhibitor. The two other types of polyamine
      inhibitors used in this study were not effective for decreasing the % parasitemia
      of Plasmodium berghei. Only DSG was available and the survival time of mice
      increased. The antiprotozoal effects shown by DSG-even this chemical is an
      immunosuppressive agent-suggest that there is a relation between the inhibition
      of the polyamine synthetic pathway or immunosuppression of DSG and the
      suppressive effect of malarial parasites.

PMID- 8996740
TI  - Binding of aminoglycoside antibiotics by degranulating mast cells.
AB  - The aminoglycoside antibiotics are polycationic at physiological pH and hence do
      not enter most cells. Indeed, when intact mast cells were incubated with
      gentamicin or tobramycin, extremely low concentrations of the two drugs could be
      measured. In contrast, when a controlled, specific degranulation of mast cells
      was induced by treating the cells with compound 48/80, Adriamycin or concanavalin
      A, a dose-dependent histamine release was observed and a significant increase of
      the intracellular concentrations of the aminoglycosides resulted. The uptake of
      gentamicin and tobramycin was not dependent on the type of stimulus, but was
      proportional to the quantity of histamine release. The aminoglycoside binding to
      granular material obtained from sonicated cells was similar to that of
      degranulating mast cells. These data suggest the occurrence of ionic interactions
      between the positively charged groups of the aminoglycosides and the negatively
      charged groups of granular matrix that are exposed as a consequence of
      exocytosis. The significant of this phenomenon is at present unclear but studies
      are in progress to clarify the fate of the aminoglycosides bound to mast cells.

PMID- 8996741
TI  - In vitro effect of hyperthermia on chemoenhancement and uptake of cisplatin in
      human pharyngeal carcinoma KB cells.
AB  - The purpose of this study was to assess the efficacy of hyperthermia (42 or 44
      degrees C) as a modifier of cis-diamminedichloroplatinum (II) (CDDP) cytotoxicity
      and platinum incorporation in human pharyngeal carcinoma KB cells. To maximize
      the interactive effect, we examined the time sequence of high (above 43 degrees
      C) or low (below 43 degrees C) hyperthermia and CDDP. Within the dose range of
      CDDP studied, there was a marked synergism between the effects of heating at 44
      degrees C and subsequent CDDP exposure for 5 h. Pretreatment at 44 degrees C for
      30 min or at 42 degrees C for 4 h enhanced CDDP cytotoxicity more than
      posttreatment at 44 degrees C for 30 min or at 42 degrees C for 4 h. However, the
      chemoenhancement ratio of pretreatment at 44 degrees C for 30 min was higher then
      that of pretreatment at 42 degrees C for 4 h, although the thermal isotoxic dose
      decreased the cell count to 60% under both conditions. There was a significant
      increase in CDDP uptake after hyperthermia at 44 degrees C. These results
      indicate that high hyperthermia effectively enhances subsequent CDDP cytotoxicity
      in human pharyngeal carcinoma KB cells.

PMID- 8996742
TI  - Legionella pneumophila pneumonia associated with acute respiratory distress
      syndrome successfully treated with imipenem.
AB  - Although utility of beta-lactams in the treatment of legionnaire's disease could
      not be demonstrated, clinical cures of human legionellosis with imipenem have
      been reported. We report the case of a 45-year-old man who presented clinical and
      radiological features of 'typical' bacterial pneumonia. He was successfully
      treated with imipenem. Serologic studies showed seroconversion for Legionella
      pneumophila.

PMID- 8996743
TI  - Low-dose, single-shot perioperative antibiotic prophylaxis in colorectal surgery.
AB  - Reductions of frequency of administration and dosage of antibiotic agents used in
      colorectal surgery may lower costs and the occurrence of adverse side effects. In
      a prospective randomized trial we evaluated two single-short regimens, a low dose
      of 1 g cefotiam against a standard dose of 2 g cefotiam, both in combination with
      500 mg metronidazole. The low-dose group had twice the number of patients with
      wound sepsis (4 of 30) than the group receiving the standard antibiotic regimen
      (2 of 30). Two hours after infusion, the antibiotic concentrations in samples of
      serum, subcutaneous fatty tissue, and colonic wall of those patients receiving 1
      g cefotiam were < 1 mg/l. The concentrations after administration of 2 g cefotiam
      were higher, as expected, and without any adverse side effects. In conclusion, we
      prefer infection prophylaxis by the standard dose of 2 g cefotiam plus 500 mg
      metronidazole in colorectal surgery.

PMID- 8996744
TI  - Comparative study on vaginal or oral treatment of bacterial vaginosis.
AB  - The bacterial epidemiology of bacterial vaginosis (BV) and the efficacy of
      vaginal or oral treatment of BV with clindamycin (CLDM) were investigated. The
      epidemiology of BV was investigated in 100 symptomatic women before CLDM therapy.
      Two groups consisting of 50 patients each with the diagnosis of symptomatic BV
      were treated with either oral administration of 450 mg CLDM three times daily or
      2% CLDM phosphate in vaginal cream (self-made) 5 g once a day, for 7 days. There
      was no significant differences in efficacy among vaginal and oral therapies with
      CLDM. Vulvovaginal irritation occurred in 3 patients orally treated and in 1
      patient vaginally treated. Gastrointestinal disturbances were observed in 4
      orally treated patients. A slight abnormal elevation of the glutamine-oxaloacetic
      transaminase level was also found in 1 patient orally treated. Since there were
      no statistically significant differences in efficacy rates between vaginal and
      oral CLDM treatments, we favor vaginal treatment of BV, based on less adverse
      effects.

PMID- 8996746
TI  - Repeated HLA mismatches and second renal graft survival in centers of the South
      Eastern Organ Procurement Foundation.
AB  - To determine if repeated HLA mismatches and other putative risk factors were
      predictive of second graft failure in second grafts performed at Southeastern
      Organ Procurement Foundation (SEOPF) members centers, we identified a cohort of
      753 retransplants in which one or more HLA antigens were mismatched in primary
      grafts. Of this group, 158 (21.1%) received second grafts with repeated
      mismatches of one or more HLA-A, B, or DR antigens that were previously
      mismatched in the primary graft (RMMs). All regrafts were cadaveric kidneys
      transplanted between 1982 and 1995. Multivariate analysis of 19 covariates in 438
      regrafts identified four independent factors that were predictive of graft
      survival frequency in second transplants. Three of the four factors were
      associated with a reduced risk for graft loss in retransplants: cyclosporin A
      (CsA) use in graft (p = 0.0001, RR = 0.26), peak PRA < 50% (p = 0.008, RR = 0.52)
      and white donor race (p = 0.035, RR = 0.63). One factor was associated with an
      increased risk of second graft failure, namely, blood transfusion prior to the
      first graft (p = 0.026, RR = 5.14). None of the other 15 factors exerted
      significant additional risk to regraft survival frequency in these SEOPF data. In
      multivariate analysis, RMMs were not associated with altered graft survival
      frequency in regrafts (p = 0.944, RR = 0.99). We than used univariate analyses to
      determine whether RMMs had adverse effects on GS in particular subsets of
      recipients that were thought to be at increased risk for the second transplant
      failure. Univariate analyses were performed with methods that are sensitive to
      early events (Wilcoxon) and late events (log-rank). The variables tested were CsA
      use for the regraft, duration of primary graft function, panel reactive antibody
      levels (PRA), immunopathologic cause of first graft failure, and HLA mismatch of
      the second graft. These analyses indicated that repeated HLA mismatches were not
      an associated risk factor in any of these subgroups. These SEOPF data indicate
      that RMMs are not predictive of increased frequency of graft loss in cadaveric
      donor second transplants. We conclude that our results do not support a policy of
      routine avoidance of RMMs, which may result in increased waiting time for a
      second donor without providing an improved graft survival rate. The available
      literature suggests that HLA antibody identification, the use of sensitive flow
      cytometric and antiglobulin-augmented cross-match tests, together with
      appropriate donor selection, optimal immunosuppression and patient management may
      be sufficient to avoid the early loss of second grafts.

PMID- 8996745
TI  - Changing patterns of bacterial nosocomial infections: a nine-year study in a
      general hospital.
AB  - Surveillance data on 12,944 bacterial isolates derived from nosocomial
      infections, reported to the Department of Microbiology and Infectious Diseases of
      the Hellenic Air Force and VA General Hospital over a 9-year period (1986-1994),
      were analyzed by the use of a microbial infection control software system.
      Overall, the isolation rate of Escherichia coli decreased from 25.2% in 1986 to
      18.2% in 1994 and Proteus spp. from 5.3 to 2.6%. Remarkably, Pseudomonas spp.
      increased from 7.2 to 11.3%, Enterobacter spp. from 1.6 to 5.1%, Klebsiella spp.
      from 5.9 to 7.8% and Enterococcus spp. from 3 to 7.4%. Interestingly, the above
      phenomenon was paralleled by a significant increase in resistance rate to various
      antibiotics. Specifically, Staphylococcus aureus and coagulase-negative
      staphylococci, though they did not display any significant variation in isolation
      rates, showed an alarming increase in resistance rate to oxacillin, from 11 and
      21% in 1986 to 51 and 75% in 1994, respectively. Enterococcus spp. sensitivity to
      vancomycin remained unlatered at 90%. The above-mentioned serious shift towards
      more resistant bacteria should be a matter of consideration.

PMID- 8996747
TI  - CREG matching for first cadaveric kidney transplants (TNX) performed by SEOPF
      centers between October 1987 and September 1995. Southeastern Organ Procurement
      Foundation.
AB  - The Southeastern Organ Procurement Foundation (SEOPF) data base from October 1987
      to September 1995 included 12,536 first cadaveric kidney transplants, of which
      39.5% were placed into non-white recipients (N-WR). Consequently, the SEOPF data
      offered an excellent sample in which to examine the effect of a number of
      conventional HLA-A, B versus public (crossreactive group, CREG) matching schemes
      on access and graft survival (GS). The standard applied was that 3-yr GS had to
      be greater than that of the mean GS of the racial group. Because of the excellent
      1- and 3-yr GS of 0 A, B, DR mismatched kidneys in both white recipients (WR) =
      87.9% and 82.8% and N-WR = 86.9% and 80.9%, these transplants were excluded from
      further analysis. Thereafter, the mean 1- and 3-yr GS of the remaining 7011 WR
      and 4862 N-WR, transplants used for all subsequent comparisons were 82.5% and
      72.4% for WR versus 80.9% and 63.0% for N-WR. Four different matching schemes
      were compared: 1) Class I A, B versus CREG hierarchical effect disregarding DR;
      2) 0, 1, 2B, DR versus 0-2 CREG, DR mismatching; 3) DR mismatching disregarding
      Class I A, B or CREG mismatching and 4) Class I A, B versus CREG mismatching
      stratified for DR. Two and possibly three CREG, DR mismatched groups were
      identified in which improved access and GS occurred in comparison with the 0, 1,
      and 2B, DR mismatched transplants currently receiving 7, 3 and 1 point in the
      UNOS sharing algorithm. The 1- and 3-yr GS in WR and N-WR of these groups were as
      follows: 0 CREG, 0 DR mismatches: 85.7% and 78.3% in WR (n = 385); 83.0% and
      69.4% in N-WR (n = 157). 1-3 CREG, 0 DR mismatches: 84.5% and 74% in WR (n =
      1550); 82.7% and 65.7% in N-WR (n = 1083). Based on this analysis, there may be a
      significant potential advantage of prospective Class I CREG over A, B matching
      for first cadaver kidney transplantation.

PMID- 8996748
TI  - SEOPF high-grade match algorithm: the effect of HLA matching with ROP trays in
      transplanting highly sensitized patients. Southern Organ Procurement Foundation.
AB  - The SEOPF high-grade match (HGM) algorithm for sharing kidneys was designed to
      increase utilization of kidneys for excellent HLA matches, decrease sharing for
      poor HLA matches, and improve the chances for highly sensitized patients to
      receive a kidney transplant through the use of ROP crossmatch trays. All
      retrieved kidneys from participating centers were offered to the system to be
      shared for high-grade HLA matches after six-antigen match obligations were
      satisfied with UNOS. Kidneys were shared according to HLA matches in the
      following priority: 1) 0-ABDR mismatch six - Antigen Matches. 2) 0-AB mismatch
      PRA > 40%, ROP tray negative crossmatch. 3) 0-BDR mismatch PRA > 40%, ROP tray
      negative crossmatch. 4) 0-BDR mismatch PRA < 40%. All patients with PRA's > 40%
      must be represented on the ROP tray to be considered for a shared kidney.
      Preliminary ROP tray crossmatch results must have been known for these patients
      in order to access the system. Here we report results of 126 shared kidneys using
      the HGM algorithm from January 1994 to September 1995. HLA typing concordance
      between the initial typing of cadaver donors by the donor center and repeat
      typing by recipient center was 94.7%. There were six (5.3%) typing discrepancies:
      HLA-A, no typing discrepancies; HLA-B, 2 (1.8%) typing discrepancies; and HLA-DR,
      4 (3.5%) discrepancies. A total of 34 of 126 (27%) kidneys were shared for
      patients with high grade HLA matches, PRA's > 40% and a negative ROP tray. Twenty
      eight of 34 (82.4%) shared kidneys were final crossmatch negative and
      transplanted into the intended recipient. Six of 34 (17.6%) shared kidneys were
      transplanted into backup recipients. All six of the intended recipients had
      positive final crossmatches using enhanced crossmatch procedures, such as
      antiglobulin and flow cytometry. In conclusion, the HLA concordance rate for
      shared kidneys within SEOPF was 94.7%. Kidney sharing using the HGM algorithm was
      very effective in transplanting highly sensitized patients when good HLA matching
      was combined with a negative ROP tray result.

PMID- 8996749
TI  - Utility of DRB1 subtyping: a case report.
AB  - The purpose of presenting this case is to illustrate the importance of high
      resolution DNA Class 2 typing when assignment of MHC antigens is of extreme
      importance (i.e. bone marrow transplantation); suggest this test as a substitute
      for the mixed lymphocyte culture (MLC), and provide evidence that DRB1 subtype
      mismatches may be clinically significant. Initial serological and monoclonal HLA
      Class 1 and low-resolution DNA-SSP Class 2 typing of a potential bone marrow
      transplant patient and two sisters revealed all to be HLA identical with apparent
      homozygosity for DRB1 x 04. High-resolution DNA-SSP Class 2 typing was then
      performed and revealed electrophoretic banding patterns which were not specific
      for any DRB1 x 04 subtype. One sister and the patient had identical patterns,
      while the other sister had a different pattern. Complete HLA Class 1 and high
      resolution DNA-SSP Class 2 typing of the parents was performed. The mother was
      found to be heterozygous for Class 1 and Class 2 antigens and possess the DRB1 x
      0404, 0405 subtypes. In contrast, the father was found to be homozygous for Class
      1 antigens, heterozygous for Class 2 antigens and possess the DRB1 x 0404, 0407
      subtypes. This led to the initial false assumption of HLA identity for the
      patient and her two sisters. However, assignment of haplotypes revealed one
      sister to be HLA identical with the patient and the other sister to be a one
      haplotype five-antigen match with the patient, mismatching for one DRB1 allele.
      Bone-marrow transplantation was performed utilizing the latter sister, which
      resulted in intractable acute graft vs. host disease that resulted in the
      patient's demise.

PMID- 8996750
TI  - Flow cytometry crossmatching and primary cadaver kidney graft outcome: relevance
      of T and B cell targets, historic sera and autologous controls.
AB  - There is limited information regarding the role of flow cytometry crossmatching
      (FCXM) in primary cadaver kidney allografting and even less about B cell
      reactivity and graft survival (GS). Furthermore, there is little or no published
      data concerning reaction strength (cutoff value), the effect of historic sera
      reactions, and the usefulness of performing autologous crossmatches (XMs) on GS.
      These factors were examined retrospectively on 214 primary transplants performed
      from August 1991 to January 1994 with follow-up to July 1995. Three-color FCXMs
      were done on a 1024-channel BD-FACScan, and the shift in median channel
      fluorescence (MCF) over the negative control was calculated. All patients had a
      negative T cell (AHG) and warm B cell (2 was, extended incubation) cytotoxicity
      XM, and none was excluded in calculating GS. A quantitative effect was noted as
      stronger MCF shifts vs. T or B cells correlated with decreased GS (r = 0.98 and
      0.92, respectively). Significant differences were seen with cutoff values of T =
      50 and B = 110 which were 1.7-1.8 times the SD above the mean MCF of normal sera
      controls T neg patients (n = 198) and 1- and 3-yr actuarial GS of 86% and 79%
      compared to T pos patients (n = 16) of 75% and 49%, p = 0.008. B neg patients (n
      = 177) had 1- and 3-yr GS od 86% and 81% compared to B pos patients (n = 37) of
      78% and 47%, p = 0.005. Most informative was the analysis of combined T and B
      cell FCXM results. Three years GS for T neg - B neg patients (n = 171) was 81%
      and for T pos - B neg patients (n = 6), it was 83%, p = 0.98. The 27 T neg - B
      pos group's GS was lower at 62% but did reach significance. Poorest GS was seen
      for T pos - B pos patients (n = 10) at 23%, p = 0.0001. Reaction patterns showed
      that T cells detected only HLA Class I antibodies, whereas B cells detected both
      Class I and II. Historic sera (> or = 1 month old) reactivity influenced GS.
      Patients with > or = 2 past sera positive but current serum negative reactions
      vs. T or T plus B cells (n = 7) had a poor 29% GS, while those historically
      positive only vs. B cells (n = 7) had 100% GS. On the other hand, patients
      positive only with the current serum (n = 16) had 2-yr GS of 100% (false positive
      test?), while patients whose current and historic sera reactions were positive (n
      = 21) had a 25-50% GS (true positive test?). About 1 in 15 patients (19%)
      displayed positive autologous FCXM reactions. Subtraction of autologous MCF shift
      values from those vs. the donor converted 17 patients to the T neg - B neg or T
      pos - B neg group whose 2-yr actual GS was not significantly different (p > 0.8)
      from those initially testing T neg B neg vs. their donors.

PMID- 8996751
TI  - T10B9 (MEDI-500) mediated immunosuppression: studies on the mechanism of action.
AB  - The murine IgM anti-human CD3/TCR mAb T10B9 is an effective agent for the
      reversal of acute cellular renal allograft rejection which offers several
      advantages over conventional OKT3 therapy. These include reduced morbidity and a
      more rapid decrease in serum creatinine levels. In the studies presented here
      comparing T10B9 and OKT3, soluble T10B9 is shown to be a nonactivating anti-T
      cell mAb. Evidence for its lack of activating potential includes in vitro failure
      to stimulate PBMC proliferation either alone or in the presence of nonmitogenic
      doses of phorbol ester, failure to induce the expression of early and late
      activation antigens and failure to induce IFN-gamma, TNF-alpha, IL-6 or IL-2
      release. Analysis of acute renal allograft rejection patient plasma cytokine
      levels 2 h after the first dose support the hypothesis that T10B9 has reduced
      immunoactivation activity in vivo. Both TNF alpha and IFN gamma patient plasma
      levels are significantly reduced in T10B9 as compared to OKT3 therapy. However,
      T10B9 is capable of cellular signaling as demonstrated by its ability to induce
      apoptosis and IL-2 release in the human T cell line Sup-T13. Thus T10B9 retains
      the potent immunosuppressive activity of OKT3 with reduced immunoactivation.

PMID- 8996752
TI  - OKT3 induction therapy: influence of duration on rejections and infections.
AB  - Anti-lymphocytes induction therapy in renal transplants remains controversial
      relative to efficacy and cost benefit. It has been suggested that shortening the
      duration of induction therapy from 14 to 7 d would provide adequate efficacy at
      less cost. Our objective was to compare the efficacy and complications of short
      (7 d or less, group A) versus standard (14 d or more, group B) duration of OKT3
      induction therapy in renal allograft recipients. We performed a retrospective
      review of all renal allografts performed between July 1989 and September 1994.
      Two groups were identified based on the duration of OKT3 induction therapy. There
      were no significant differences between group A or B in the distribution of age,
      sex, race, degree of HLA matching, and etiology or renal failure. Patients in
      group B experienced fewer rejections at 3 and 12 months (p = 0.0236 and p =
      0.0065, respectively) as well as fewer viral infections during the first year of
      follow-up (p = 0.0435). No difference on the mean number of bacterial or fungal
      infections existed between the two groups. There were no statistically
      significant differences in patient or graft survival, although patients in group
      B had a tendency towards increased 1-yr graft survival.

PMID- 8996753
TI  - Effects of azathioprine withdrawal in kidney recipients with stable function two
      years after transplant.
AB  - To assess the effects of azathioprine withdrawal, renal recipients with grafts >
      2 yr function (103 study patients) were tapered off azathioprine over a 1-yr
      period and compared to 69 patients 2 yr after transplant who were not tapered
      (controls). Of the 103 study patients, 16 (15%) were living-donor transplants and
      87 were cadaveric. Of the 69 control patients, 9 (13%) were living related
      transplants and 60 were cadaveric. The mean HLA match for those tapered was 3.3
      Ag and 3.1 Ag for those remaining on azathioprine. Two study patients restarted
      azathioprine on their own. Age, sex, and cause of renal failure in both groups
      was similar. Of the 101 study patients remaining, 9 (8.8%) returned to dialysis
      due to biopsy proven chronic rejection. There were no acute rejection episodes.
      Six of the 69 control patients (8.7%) also returned to dialysis for the same
      reason. Of the 92 patients who have completed the taper, 85 have been off
      azathioprine for six or more months. There was not a significant difference
      between the mean 12- and 24-month creatinine levels of the study patients (1.6
      mg%, 1.7 mg%) and those of the controls (1.5 mg%, 1.8 mg%). The mean 12- and 24
      month hematocritis of patients tapered (41.3%, 40.8%) were comparable with
      patients not tapered (42.3%, 42.8%). Of interest, the mean hematocritis of both
      study and control patients rose from 28.9% and 33.5%, respectively, to 41.3% and
      42.3% 1 yr following entry into the study. The mean 12- and 24-month white blood
      counts of those tapered (8.9, 8.7) did not differ significantly from those
      continued on azathioprine (8.8, 8.8). In stable renal transplant patients on
      triple drug immunosuppression for at least 2 yr, azathioprine can be
      discontinued, in a tapered protocol, without an increased risk of graft loss or
      compromise of renal function.

PMID- 8996754
TI  - Immunogenetic factors that may contribute to ethnic differences in renal
      allograft survival.
AB  - In the United States, allocation of cadaveric kidneys is federally regulated and
      based on the concept of equal access to all patients, regardless of race, sex,
      age, or socioeconomic status. Nevertheless, it has been widely reported that
      African American patients with renal disease wait longer for kidney
      transplantation and, once transplanted, have poorer graft survival. We have
      assessed immunogenetic factors that may contribute to ethnic differences in
      allograft survival by examining the distributions of ABO blood groups, HLA
      antigens and haplotypes, percent reactive antibody (PRA), age, and gender in our
      local patient population. Approximately 62% of patients at our transplant center
      waiting for renal transplantation are African American; 39% are female. Age
      distribution is comparable to that reported nationally. ABO blood groups of
      patients on the waiting list are distributed similarly to those reported
      nationally for other renal patients. Sensitization to HLA antigens, through
      either blood transfusion, prior transplant, or pregnancy, has been strongly
      associated with poorer graft survival. Although, as expected, distribution of PRA
      was significantly different for males versus females at one time point, it did
      not differ between ethnic groups in our patient population. HLA polymorphism was
      assessed by comparisons of HLA allele and haplotype frequencies determined by
      analyses of African American and Caucasian families typed in our program since
      1991. Haplotypes observed in each ethnic population were subjected to a variety
      of statistical analyses. Coefficient of contingency and Cramer's V statistic
      (measures of degree of association) were consistently higher for Caucasian
      haplotypes than for those of African Americans. Significantly more unique HLA
      haplotypes were observed among African American families than among Caucasian
      families. Thus, our data provide evidence for greater HLA linkage disequilibrium
      in Caucasians than in African Americans. HLA antigen and haplotype polymorphisms
      are likely, therefore, to be major immunogenetic factors contributing to ethnic
      differences in renal allograft survival.

PMID- 8996755
TI  - Disproportionate HLA matching may contribute to racial disparity in patient
      survival following cardiac transplantation.
AB  - The purpose of this study is to investigate the impact of recipient race as well
      as HLA matching upon long-term survival following heart transplantation (HTx).
      The study also determines whether the degree of HLA matching between Caucasians
      and African Americans differs. This study was a retrospective analysis of 336
      males (77% Caucasians and 23% African Americans) transplanted between 1983 and
      1994, all having received cyclosporine-based immunosuppression. The results
      showed African Americans were transplanted at a significantly younger age than
      Caucasians (39.1 +/- 11.2 vs. 48.2 +/- 10 yr). The composition of end stage
      cardiac disease was startlingly different. Caucasians demonstrated 62% CAD, 31%
      IDCM and 7% other, whereas African Americans exhibited 24% CAD, 69% IDCM and 7%
      other. The ten-year survival rate for African American male recipients was
      inferior to Caucasian males. Survival at 1, 3, 5, 7 and 9 yr was 83%, 73%, 63%,
      51%, 46% for Caucasians and 70%, 58%, 51%, 38% and 32% for African Americans.
      Furthermore, African Americans received more poorly matched organs compared to
      Caucasians. Among Caucasians for Class I, 46%, 53% and 1% received poor, moderate
      and well matched hearts, respectively. In contrast, African American were
      allocated 65%, 33% and 0% of poor, moderate, or well matched hearts. An analysis
      of Class II data revealed the same pattern (63%, 35% 2% of Caucasians and 78%,
      18%, and 4% of African Americans received poor, moderate or well matched hearts).
      Survival for Caucasians improved when moderately versus poorly matched for Class
      I. Class II matching did not have an effect. African Americans showed a similar
      trend, although statistical significance was not reached. When comparing
      equivalent degrees of matching, African Americans had inferior survival rate when
      poorly matched for Class I relative to Caucasians. No statistical difference was
      observed for moderate matched Class I or for Class II analysis.

PMID- 8996756
TI  - Routine early biopsy of allografts with delayed function: correlation of
      histopathology and transplant outcome.
AB  - Approximately 25-30% or our cadaveric renal transplant recipients have required
      post-transplant dialysis. In an attempt to discern the etiology, routine biopsies
      were performed 7-10 d post-transplant and repeated weekly. All patients received
      a triple-therapy cyclosporine-based regimen with (N = 61) or without (N = 10)
      antilymphocyte induction. Rejection was classified as 'early' when it appeared on
      the first biopsy (8.9 +/- 0.3 d), 'delayed' when it appeared only on the second
      biopsy (17.9 +/- 1.0 d) and persistent when present on both biopsies. Adequate
      biopsy material was obtained from 71 patients who provided a total of 117
      biopsies. Acute tubular necrosis was the most common finding (50%) in the first
      biopsy, while rejection occurred in 30% of biopsies. Rejection on the first
      biopsy was strongly associated with primary nonfunction (PNF) (8 of 21 vs. 1 of
      40, p < or = 0.0001). In contrast, eight patients without rejection on Biopsy 1
      developed delayed rejection on Biopsy 2; only one was associated with PNF. DGF
      persisted beyond the second week in 38 patients; 17 (38%) of which had rejection.
      Nine patients had persistent rejection 55% of whom experienced PNF compared to 6%
      without persistent rejection (p < or = 0.001). The occurrence of early rejection
      was associated with pretransplant peak PRA levels > 50% (p < or = 0.01). Graft
      survival for all patients was 79% and 65% at 1 and 2 yr. Rejection influenced 1
      yr graft survival for patients with persistent rejection who had 55% incidence of
      primary nonfunction and 1- and 2-yr graft survival rates of 42% and 37%. These
      data indicate that early biopsies are useful in unmasking rejection during DGF
      and at predicting primary nonfunction. Based on these data we recommend the
      routine utilization of biopsies for all patients with DGF.

PMID- 8996757
TI  - Renal allograft rupture: a clinical review.
AB  - Rupture of a renal allograft (RAR) is an uncommon but serious complication of
      renal transplantation. A recent RAR prompted a review of our experience, with the
      purpose of (1) identifying conditions that may predispose this complication and
      (2) defining strategies for prevention. A 5-yr, consecutive living-related (LRD)
      and cadaver donor (CD) cohort of 331 patients was studied retrospectively. Twelve
      patients (3.6%) had RAR. Donor characteristics, procurement and preservation
      conditions, and recipient characteristics were major study categories. Data
      analysis was computer-based and included multivariate analysis. The nine White
      and two Black cadaver donors were "ideal", mean age 29 yr, with mean high
      creatinine (CR) of 1.3 and terminal CR of 1.1 mg/dl and mean terminal urine
      output of 423 ml/min. Nine of 11 CD had low-dose dopamine use (terminal, mean 8,
      range 5-13 micrograms/kg/min). Eleven of 11 donors had procurement en-bloc, 9 of
      which were multiple organ procurement. All had 4+/4+ flush and cold storage with
      UW solution. Mean cold ischemia time (CIT) was 22 h, 28 min (range 15 h, 16 min
      to 40 h). For patients with RAR mean age was 39 yr; there were 12 Black patients
      and 7 males, 5 females. HLA match was 1 antigen (AG) for 3, 2 AG for 8, and 4 AG
      for 1 (mean 1.9). Nine patients had delayed or declining renal function requiring
      dialysis. The panel reactive antibody was at peak, mean 47% (range 0-100%) and
      current, mean 18% (range 0-84%). Six of 12 had OKT3 therapy at time of RAR and
      six had biopsies. Day of RAR was mean 10, median 9 (range 4-21). Pain and drop in
      hematocrit were observed in most. There was one fatality (8%), and all kidneys
      were removed. All kidneys showed at least minimal rejection but six had severe
      acute tubular necrosis (ATN) with edema and minimal rejection. Statistically
      significant associations with RAR were older recipient age (p = 0.01), donor
      recipient race mismatch (White donor to Black recipient) (p = 0.007), and
      dialysis requirement (p < 0.001). Other variables were not statistically
      correlated: gender, race, CIT, transplant number, LRD vs. CD, peak or current
      PRA, and total HLA and BDR mismatch. The data suggest that ATN and rejection act
      synergistically to cause RAR and that early delayed function requires intensive
      and perhaps novel immunosuppression, especially in Black recipients.

PMID- 8996758
TI  - Donor-specific HLA antibodies after transplantation are associated with
      deterioration in cardiac function.
AB  - Although there is increasing evidence that mismatched donor HLA antigens are
      associated with a lowering of survival of human cardiac allografts, the effect of
      antibodies that bind those antigens is less clear. The existence of
      lymphocytotoxic antibodies prior to cardiac transplantation has been associated
      with a poor outcome in the majority of reports of relevant studies, as has their
      appearance post-transplantation. But how such antibodies, especially those with
      HLA specificity, cause poor outcomes has been poorly understood. The purpose of
      this study was to investigate the effect of anti-HLA antibodies appearing in the
      circulation after human orthotopic heart transplantation. Such antibodies were
      identified by a standard microlymphocytotoxicity technique using panels of frozen
      lymphocytes from normal donors who had been tissue typed. Of 74 patients
      transplanted over a 12-month period, 4 (5.4%) developed alloantibodies specific
      for mismatched donor HLA antigens. The first patient developed antibodies to HLA
      A23 and B44 together with poor ventricular function and vascular rejection
      requiring retransplantation within 4 months. The other patients (3) developed
      antibodies specific for HLA-DQ antigens and experienced variable numbers of
      episodes of cellular rejection with no evidence of vascular rejection on
      endomyocardial biopsy. Two of these three patients died (8 and 11 months post
      transplant) after three and six rejection episodes, respectively. The one
      surviving patient had seven rejection episodes and continues to have poor
      ventricular function 18 months post-transplant. We conclude that alloantibodies
      specific for mismatched donor HLA antigens may have a deleterious effect on the
      outcome of the human cardiac allograft and should be monitored closely post
      transplant. Furthermore, such antibodies may mediate effects on the transplanted
      heart which are not detectable in specimens obtained by endomyocardial biopsy.

PMID- 8996759
TI  - Immunohistochemical manifestations of unilateral kidney ischemia.
AB  - Events in the early post-transplant period have been correlated with increased
      renal allograft loss. Immunologic reactions and ischemic injury have been
      implicated in this process. While the immunologic aspects of allograft injury
      have been studied extensively, ischemic effects remain less well understood. To
      study the effects of ischemia in rats with different genetic backgrounds without
      the introduction of an alloimmune response, a clamp was placed on the vascular
      pedicle of the left kidney for 60 min. The short-term effects (1 wk) of ischemia
      were studied in groups of PVG (RT1c), LEW (RT1), DA (RT1a) and WR (RT1u) rats,
      Immunoperoxidase staining demonstrated limited infiltration of monocytes,
      macrophages, and T-cells accompanied by upregulation of low levels of MHC class
      II antigens on tubular epithelial cells, peritubular capillaries, and
      interstitial cells in kidneys of PVG and WF rats. Kidneys of LEW and DA rats had
      greater influxes of monocytes, macrophages, and T cells in addition to higher
      amounts of MHC class II antigens upregulation on tubular epithelium and
      interstitial cells. The long-term effects of ischemia were studied in kidneys of
      WF rats. These kidneys had a progressive increase in infiltrating T cells,
      monocytes, macrophages and MHC class II expression on the tubular epithelium and
      the interstitial cells at 14, 30, and 90 d after the ischemic insult. The
      differences in MHC class II expression between ischemic kidneys of PVG and LEW
      rats were not associated with differences in production of mRNA for IL-2, IFN
      gamma, and TNF-alpha. In summary, transient renal ischemia in the absence of an
      allogeneic immune response triggers a progression of inflammatory responses,
      including leukocyte infiltration, cytokine production and MHC class II antigen
      upregulation which appears to be strain-dependent.

PMID- 8996760
TI  - A new approach for increasing the organ supply.
AB  - The donation of organs and tissues for the benefit of another person is an
      altruistic act and one that is a guaranteed option for the next-of-kin through
      various national Required Request legislations. At the Washington Hospital Center
      we have developed an approach that permits organ recovery from non-heart beating
      donors. The focus is on victims of fatal trauma and assures that each family is
      empowered with the right to make a donation decision. In October 1993 a consensus
      conference was held on implementing a program to recover organs from fatal trauma
      victims. The participants recommended that safeguards be incorporated to assure
      ethical treatment of both the trauma victim and the next-of-kin. An Office of
      Decedent Affairs (ODA) was then established and implemented in September 1994.
      The ODA is staffed by Family Advocates who are on duty continuously and respond
      to all trauma and death events. Their mission is to consolidate all death events,
      provide support to decedent families, assure that required request mandates are
      fulfilled, interact with the local Organ Procurement Organization (OPO) in the
      consent process, and facilitate the implementation of the Rapid Organ Recovery
      Program (RORP). The RORP consists of two specific procedures: cannulation of the
      femoral arterial-venous system for flushing the kidneys with a preservative
      solution, and intubation of the peritoneum for in situ cooling using an
      ice/lavage process. In the 1-yr period since the ODA was established, organ and
      tissue donation has increased by more than 300%.

PMID- 8996761
TI  - Evidence that ursodeoxycholic acid prevents steroid-resistant rejection in adult
      liver transplantation.
AB  - Steroid-resistant rejection continues to be a serious problem in liver
      transplantation. Since ursodeoxycholic acid (UDCA) is beneficial in several
      cholestatic disorders and possesses in vitro immunomodulatory and
      immunosuppressive effects, we have tested in a pilot study the effects of
      adjuvant UDCA in the prevention of steroid-resistant rejection. Fifty consecutive
      liver transplant patients were treated with a standard cyclosporine
      immunosuppressive regimen. Treatment with UDCA (10 mg/kg/d) was initiated in each
      patient who developed biopsy-proven rejection or biochemical evidence of
      cholestasis. Clinical and laboratory features were monitored for evidence of
      rejection. Data were analyzed after at least a 10-month follow-up period was
      available in each patient. Seven patients died during the study period, all
      within 4 wk of surgery. No evidence of rejection was documented in these
      patients. Twenty three of the 43 survivors 53% (23/43) developed an episode of
      rejection, and UDCA was initiated in each of them. Only one patient had a second
      episode of rejection, which responded to intravenous methylprednisolone therapy;
      no patient required antilymphocyte therapy. There was no evidence of toxicity for
      UDCA. These data suggest that UDCA can be given safely following OLT and may
      contribute to prevention of steroid-resistant rejection in liver transplant
      recipients.

PMID- 8996762
TI  - Prevention of hepatitis B recurrence with indefinite hepatitis B immune globulin
      (HBIG) prophylaxis after liver transplantation.
AB  - Liver transplantation for hepatitis B is followed by a high rate of recurrence
      some time after transplantation, resulting in poor outcome compared to liver
      recipients transplanted for other indications. Passive immunoprophylaxis with
      HBIG has been shown to decrease the rate of recurrence to 25-50%, but the
      intensity and length of treatment is still controversial. We studied 17 HBsAg
      positive patients who were transplanted for hepatitis B. Four did not receive
      immunoprophylaxis and they all reoccurred within 3 months. The remaining 13 have
      received indefinite, high dose HBIG (10,000 mu or 40,000 mu/dose depending on HBV
      DNA status pretransplant). Ten of 13 patients (77%) remain HBsAg negative after a
      mean follow-up of 16.7 months with six of these ten patients being HBV DNA
      positive pretransplant. Of the three who have experienced recurrence, two
      received extensive additional immunosuppression beyond that normally administered
      to transplant patients (chemotherapy, multiple antirejection treatment). The last
      patient received 110,000 u of HBIG during the first 3 months, which produced an
      anti-HBs titer level of 225 IU/L, but the following month he was HBsAg positive
      with an anti-HBs titer of 13 IU/L. We conclude that HBsAg positive patients can
      be safely transplanted using indefinite, high-dose HBIG prophylaxis, and that
      with adequate HBIG it is possible to prevent recurrence in HBV DNA positive
      patients as well.

PMID- 8996763
TI  - Liver transplantation for hepatitis B cirrhosis: clinical sequela of passive
      immunization.
AB  - Aggressive administration of hepatitis B immune globulin (HBIg) has been shown to
      prevent hepatitis B viral (HBV) infection of the allograft; however, the clinical
      sequela of such therapy has not been previously described. We reviewed our
      experience with high dose, intravenous infusion of an intramuscular HBIg
      preparation to assess the effectiveness and complications of such therapy. Thirty
      three orthotopic liver transplants (OLTx) were performed in 32 patients with
      chronic HBV cirrhosis at the University of Virginia between March 1990 and June
      1995. Twenty-nine of 32 (91%) patients remain free of HBV recurrence (defined by
      undetectable serum HBsAg and HBV-DNA) after a mean of 21 months (2-54 months),
      with one patient requiring retransplantation. Three (10%) patients died of non
      HBV causes (two vascular events, one infectious event). Twenty episodes of acute
      cellular rejection were treated in 18 patients (two had two episodes). Sixteen
      rejections occurred within 18 d of transplant, 19 by day 120, and one late
      rejection occurred at 18 months owing to medication non-compliance. Eighteen
      patients had at least one documented infection. Six patients were treated for CMV
      infection (five empirically). Eight patients were treated for HSV infections
      (seven mild herpetic labialis and one herpetic keratitis). Four patients had
      documented fungal infection (one mucormycosis pneumonia and three minor
      superficial mucosal infections). With the exception of one necrotizing pneumonia,
      11 bacterial infections were successfully treated with conventional antimicrobial
      agents. No patient developed post-transplant lymphoproliferative disorder.
      Symptoms associated with HBIg infusion were intermittent but frequent and
      consisted of myalgias, predominantly back pain (90%), headache (20%) and flushing
      (5%). No patient experienced anaphylaxis, fever, rash, arthritis or hypotension.
      Despite the potential for mercury toxicity and HCV transmission in the HBIg
      formulations currently available in the United States, serum mercury levels
      remained below standards for industrial exposure (60 micrograms/ml), and only one
      individual developed post-transplant HCV infection after receiving multiple units
      of unscreened blood prior to 1991. SUMMARY: High-dose HBIg prevented HBV
      infection of the allograft in 29 of 32 patients transplanted for HBV cirrhosis
      with three non-HBV associated deaths. The intravenous infusion of HBIg was
      frequently associated with minor side effects that were safely tolerated by
      patients. The risk of HCV transmission and mercury toxicity are minimal, but
      support the need for a new intravenous formulation of HBIg. HBIg therapy
      successfully decreased post-OLTx HBV recurrence with no clinical events
      associated with immunosuppression. Patients did non experience allergic or
      infusion-related complications that altered or terminated therapy. Manufacturing
      modifications of HBIg may allow for improved patient tolerance and decreased
      risks.

PMID- 8996764
TI  - Liver transplantation for alcoholic liver disease.
AB  - Orthotopic liver transplantation (OLT) for individuals with alcoholic liver
      disease (ALD) remains controversial. This review was designed to evaluate the
      survival, recidivism, and rehabilitation of the alcoholic liver transplant
      recipient in a single transplant center. METHODS: Between 10/86 and 11/92 203
      liver transplants were performed in 179 patients. In 42 patients (23%) the
      primary etiologic diagnosis was ALD (36 males, 6 females, median age 47 yr). All
      ALD patients were evaluated preoperatively by social service, psychiatry, and
      medical psychology, in addition to hepatology and transplant surgery. A minimum
      abstinence period of 3-6 months was encouraged, although exceptions were made for
      cases of extreme medical urgency in which a good prognosis for abstinence was
      predicted. RESULTS: In OLT recipients with ALD, actuarial survival at 1, 2, and 3
      yr was 74%, 71%, and 71%, respectively, compared to 71%, 71%, and 69% for all OLT
      recipients. One- and two-year survival was 85% in the most recently transplanted
      86 patients, 20 of whom (23%) had ALD with 1- and 2-yr survival of 84% (N.S.).
      Recidivism was monitored postoperatively by interviews with the patient and
      family, supplemented by random urine and serum toxicology. Of the 29 survivors, 2
      (7%) returned temporarily to alcohol use but are presently abstinent. Although
      none of the ALD patients in this study was able to work prior to OLT, 76% of the
      survivors at least 4 months post-transplantation were employed. CONCLUSIONS:
      Although our experience is small, our results suggest that OLT is appropriate
      therapy for carefully selected patients with end-stage liver failure due to ALD.
      The multi-disciplinary approach to preoperative evaluation of the alcoholic liver
      transplant candidate is effective in determining those patients committed to
      abstinence after a successful transplant.

PMID- 8996765
TI  - Factors on graft survival of living donor kidney transplantation in a single
      center.
AB  - We analyzed the potential factors that could influence the survival of graft,
      focused on primary graft living-donor kidney transplantation with cyclosporine
      (CsA) therapy. 680 cases were enrolled in this study. Patients and graft survival
      rates were calculated by a Kaplan-Meier product limit estimate with a 1-day time
      interval. The analyzed variables were donor relationship, HLA matching, recipient
      age and sex, donor age and sex, ABO blood type compatibility, diabetic status,
      hepatitis virus infection, donor specific or non-specific blood transfusion and
      acute rejection episode. The results suggested that acute rejection episode was
      the most prognostic factor in graft survival. An HLA-matched donor and a young
      male donor, i.e. a greater donor nephron mass for less recipient body mass, will
      show better long-term survival. Diabetes and hepatitis B infection have some
      negative effects on the long-term survival of graft kidney, but age of recipient,
      donor-specific transfusion and donor-recipient relationship have little effect.

PMID- 8996766
TI  - Heart transplantation for patients over age 60.
AB  - As the proportion of people over age 60 in our society continues to rise, so does
      the number of potential heart transplant candidates. Advanced recipient age,
      however, has long been used as an exclusion criterion for transplantation, though
      the upper age limit remains poorly defined. The purpose of our study was to
      analyze the outcomes of 31 heart transplant recipients over age 60 at our
      institution. They were followed with regard to early and late morbidity and
      mortality. Mean follow-up time was 50 months. The 1- and 5-yr survival rates were
      90% and 85%. These rates were not significantly different compared with younger
      (age 18 to 59) recipients transplanted in the same time period. The older
      recipients more frequently developed osteoporotic changes as well as cutaneous
      and visceral malignancies, but had infrequent rejection episodes. Overall, heart
      transplantation is safe and effective for patients over age 60 with end-stage
      congestive heart failure. Both 1- and 5-yr survival rates are well within the
      acceptable range and do not differ significantly from younger recipients.
      Individualized immunosuppression might help reduce the incidence of malignancy in
      older recipients, but further studies are needed. Matching donor and recipient
      age would make the best use of available organs.

PMID- 8996767
TI  - The importance of early cyclosporine levels in pediatric kidney transplantation.
AB  - We studied the impact of early cyclosporine (CSA) levels on the incidence of
      rejection in pediatric transplant recipients. Between 1 January 1984 and 31
      December 1994, a total of 234 pediatric patients underwent kidney transplants and
      received CSA immunosuppression. We analyzed the impact of CSA levels (at 1 wk, 2
      wk, 1 month, 2 months, and 3 months) on the incidence of rejection in the first 3
      and the first 6 months post-transplant. We found that CSA levels at all
      timepoints correlated, i.e. recipients with low levels in the early post
      transplant period tended to have low levels throughout the first 12 months.
      Multivariate analysis for risk factors by biopsy-proven rejection in the first 3
      months revealed that the CSA trough level was the critical factor (p < 0.05).
      Recipients with CSA trough levels < 100 ng/ml had 2.24 times the risk of
      rejections vs. those with blood levels > 100 ng/ml. Similarly, the CSA trough
      level at 1 month was the critical risk factor for biopsy-proven rejection within
      the first 6 months (p < 0.05). The major risk factor for graft loss within the
      first 12 months was a biopsy-proven rejection episode. We conclude that in
      pediatric kidney transplant recipients, early CSA trough levels < 100 ng/ml are
      associated with a significantly increased incidence of rejection in the first 6
      months post-transplant.

PMID- 8996768
TI  - Cytomegalovirus infection associated accelerated heart allograft arteriosclerosis
      may impair the late function of the graft.
AB  - Cardiac allograft arteriosclerosis is the most important limiting factor of long
      term survival of heart transplant recipients. Several clinical studies have
      suggested the association between CMV infection and heart allograft
      arteriosclerosis, chronic rejection. To determine the temporal impact of CMV
      infection on the development of heart allograft arteriosclerosis we quantitated
      coronary angiograms obtained from 72 heart transplant recipients followed for 1-6
      yr post-transplantation. To examine the graft function, echocardiography was
      evaluated. CMV infection was associated with early development of allograft
      arteriosclerosis manifested by intense diffuse pruning of the coronary arteries
      including their smallest branches already after the second post-transplant year.
      Even 6 yr post-transplantation the magnitude of arteriosclerotic changes was
      significantly higher in recipients with CMV infection compared with patients
      without infection (P < 0.02). No difference in echocardiographic parameters
      including ejection fraction (EF), left ventricular end diastolic diameter (LVEDD)
      and left ventricular mass (LVM) between recipients with and without CMV infection
      was recorded early after transplantation. However, when compared to recipients
      without CMV, the CMV accelerated chronic rejection seen in coronary angiography
      associated with impaired late graft function as judged by decreased EF in
      patients with CMV infection 6 yr post-transplantation (P < 0.02). No differences
      in LVEDD or LVM between the patient groups occurred. Taken together, these
      results suggest that CMV infection is associated with intense cardiac allograft
      arteriosclerosis affecting the whole coronary tree soon after transplantation.
      The intensity and magnitude of these chronic vascular wall changes increase and
      persist during subsequent years, indicating that the risk for graft loss and
      death due to chronic rejection is especially high during the first 5 post
      transplant years in CMV-infected patients. Echocardiography may not be a
      sensitive method to distinguish patients with early CMV-accelerated allograft
      arteriosclerosis but coronary angiography must be performed.

PMID- 8996769
TI  - A prospective study of rapid methods of detecting cytomegalovirus in the blood of
      renal transplant recipients in relation to patient and graft survival.
AB  - Eighty-five renal transplant recipients were prospectively monitored for CMV
      infection up to 4 months post-transplantation by virus isolation from leukocytes,
      CMV antigen detection (pp65) in peripheral blood leukocytes (PBL), polymerase
      chain reaction (PCR) of alkaline treated plasma (P-PCR), PCR of extracted DNA
      from PBL (L-PCR) and serology. Additionally univariate and multivariate analyses
      of risk factors for patient and graft survival up to 4 yr post-transplantation
      were performed. The incidence of CMV infection was 78% and of CMV disease 33%.
      Antigen detection in PBL was positive before or at onset of symptoms in 23/24
      (96%) evaluable patients with CMV disease. The corresponding figures for virus
      isolation were 22/24 (92%), P-PCR 21/24 (88%) and for L-PCR 18/24 (75%). The
      percentage of negative samples in patients without CMV disease was 89% for the
      antigen test, 92% for L-PCR and 83% for virus isolation and P-PCR. One rapid test
      (antigen test, P-PCR or L-PCR) was positive at a median of 16 d before the onset
      of symptoms. The antigen test was generally the first rapid test to become
      positive. CMV disease did not affect graft survival in the multivariate analysis
      but was associated with decreased patient survival.

PMID- 8996770
TI  - Foot problems in the diabetic transplant recipient.
AB  - Diabetic transplant recipients are at a high risk for foot pathology leading to
      amputation. This retrospective study from 1/85 to 2/95 examines the risk of foot
      complications in a population (n = 340) of diabetic renal and combined
      renal/pancreas transplant recipients. All groups suffered high lower extremity
      amputation and foot fracture rates. Patients with better circulation and
      protective sensation intact fared better. Smoking had a profoundly negative
      effect on the amputation rate as did an amputation prior to the transplant.
      Patients with pretransplant dialysis were at a higher risk for post-transplant
      amputation. Concomitant pancreas transplant did not in general significantly
      affect the risk of amputation or fracture. Females had almost twice the fracture
      rate of males.

PMID- 8996771
TI  - Long-term function of vascular access for hemodialysis.
AB  - OBJECTIVES: To compare the outcome of autogenous arteriovenous fistulas (AVF)
      with interposition graft fistulas for hemodialysis access. DESIGN: Retrospective
      clinical study. SETTING: Department of Surgery, Zurich University Hospital.
      METHODS: Primary and secondary patency rates were calculated by life tables.
      Factors potentially affecting patency were studied by comparison of life tables
      using the log rank test. MAIN RESULTS: From 1980 to 1992, 414 patients were
      operated on for long-term vascular access. 720 fistulas were created including
      429 AVF and 291 interposition grafts (150 bovine xenografts, 69 PTFE grafts, 59
      sheep collagen grafts, 10 autologous and 1 homologous vein grafts). Secondary
      patency rates after 1 and 3 yr were 74/64% in AVF, 56/24% in bovine xenografts,
      58/40% in PTFE grafts and 71/45% in sheep collagen grafts. The latter performed
      not significantly worse than AVF. Primary and secondary patency rates were
      significantly lower in women.

PMID- 8996772
TI  - A third kidney transplant: cost-effective treatment for end-stage renal disease?
AB  - Given the organ donor shortage, some question whether a third kidney transplant
      can be justified. We studied the outcome of 51 third transplants (mean age 28 +/-
      2 yr) done between 1 January 1985 and 31 December 1994. We compared hospital stay
      (mean +/- S.E.), cost, readmissions, readmission days, and outcome of third (vs.
      first and second) transplants. We found that patient survival for third
      transplants was equivalent to first and second transplants; graft survival was
      not as good. However, when third transplant recipients with recurrent disease
      (specifically, hemolytic uremic syndrome and focal sclerosis) were excluded from
      our analysis, we found no difference in 5-yr graft survival (vs. first or second
      transplant recipients). Of the 51 third transplant recipients, 41 had a cadaver
      donor transplant. Third cadaver transplant recipients tended to have a longer
      hospital stay (p = NS) than first cadaver transplant recipients but had no more
      readmissions or readmission days than first and second cadaver transplant
      recipients. Employment data are available for 28 third transplant recipients; 16
      (57%) are currently working or going to school. Of the 21 recipients who
      responded to quality of life questionnaires, 17 (81%) reported being healthy and
      all 21 (100%) said transplantation was not a drawback to their health. We
      conclude that third transplants should be considered for selected patients with
      renal failure whose first and second transplants have failed. Such patients can
      often be successfully transplanted.

PMID- 8996773
TI  - Volume-mediated pulmonary responses in liver transplant candidates.
AB  - Pulmonary hypertension, defined as mean pulmonary artery pressure (mPAP) greater
      than or equal to 25 mmHg, is a recognized complication of hepatic dysfunction
      with portal hypertension and is considered a relative contraindication to liver
      transplantation. To characterize pulmonary hemodynamic responses in OLT
      candidates without pre-existing primary pulmonary hypertension, 22 consecutive
      patients referred for OLT at the Stanford University Hospital underwent
      prospective right heart catheterization with pressure determinations at baseline
      and following infusion of 11 crystalloid over 10 min. In addition, EKG, chest X
      ray and transthoracic echocardiograms were performed as a part of the routine
      evaluation. Eleven non-cirrhotic patients served as controls. At baseline, 1/22
      (4.5%) OLT patients had pulmonary hypertension while 9/22 (41%) developed
      pulmonary hypertension following volume infusion (p < 0.0001). In contrast, 0/11
      controls manifested elevated pulmonary pressures at baseline or following volume
      challenge. OLT candidates were found to have significant increases in mean
      pulmonary pressure and capillary wedge pressure (PCWP) compared to controls,
      suggesting intravascular volume overload or left ventricular dysfunction as
      potential causes. OLT candidates who manifested volume-dependent pulmonary
      hypertension (a) had a 2-fold higher baseline PCWP, (b) currently smoked, and (c)
      had previously undergone portosystemic shunts. Aggregate analysis of EKG, echo
      and CXR for determination of volume-mediated pulmonary hypertension revealed a
      sensitivity of 25%, specificity of 75% and a positive predictive value of 40%.
      Preoperative identification of patients with a predisposition to manifesting
      elevated pulmonary pressures in the context of rapid volume infusion offers the
      potential for improved risk stratification and optimized clinical management.

PMID- 8996774
TI  - VCAM-1 and E-selectin expression during cytomegalovirus infection in post
      transplant myocardial biopsies.
AB  - Adhesion molecule expression may become useful in monitoring cardiac graft
      rejection, but first the question of whether expression is upregulated by
      cytomegalovirus (CMV), a common post-transplant infection, must be answered. To
      study this, all cardiac biopsies (n = 201) on 12 cardiac transplant recipients
      were examined for rejection grade and VCAM-1, ICAM-1, and E-selectin expression
      over the first 6-15 months post-transplant. Adhesion molecule expression in
      biopsies taken during documented CMV infections were compared to those taken in
      the absence of infection, both overall and sorted as to rejection grade. There
      were 17 CMV infections in this patient group. VCAM-1 was expressed in 82% of
      biopsies coincident with CMV infections, compared to 43% of biopsies unrelated to
      CMV infection, a significant difference (p < 0.01). E-selectin was expressed in
      65% of biopsies with CMV infection, compared to 30% of biopsies unrelated to CMV
      infection, also statistically significant (p = 0.01). Both VCAM-1 and E-selectin
      were expressed in 80% of biopsies without rejection taken during CMV infections,
      significantly greater than the 24% incidence of VCAM-1 and 14% incidence of E
      selectin expression in biopsies without rejection that were not concomitant with
      CMV infection. In the absence of CMV infection, both VCAM-1 and E-selectin
      expression correlated significantly with rejection grade, but this relationship
      became invalid in the presence of CMV infection. ICAM-1 expression bore no
      relation to CMV infection. VCAM-1 and E-selectin expression in cardiac biopsies
      can be upregulated with CMV infection in the absence of graft rejection.

PMID- 8996775
TI  - Impact of first acute rejection episode and severity of rejection on cadaveric
      renal allograft survival.
AB  - A total of 504 renal transplants were performed between 1984 and 1993; 408 (81%)
      were cadaver grafts. This study evaluated the impact of a first acute rejection
      episode and the severity of the rejection on cadaveric allograft survival. Acute
      allograft rejection was based on clinical evaluation and confirmed by renal
      biopsy. Ten patients were excluded from this study due to early patient or graft
      loss. Patients were divided into Group I (n = 179), who never experienced acute
      rejection, and Group II (n = 219), who had an acute rejection episode. Group II
      patients were divided into IIA (n = 140), who had a mild first acute rejection
      episode treated with methylprednisolone, and IIB (n = 79), who had moderate or
      severe acute rejection treated with OKT3. The overall 1-, 2-, 3-, and 5-yr
      actuarial cadaveric renal allograft survival for Group I was 80%, 76%, 74%, and
      68%. The corresponding graft survival for Groups IIA and IIB were 75%, 63%, 58%,
      and 50%; and 79% 71%, 65%, and 53% [p = 0.03 (I vs IIA), p = NS (I vs. IIB and
      IIA vs IIB)]. A similar pattern of survival was seen in primary kidney allograft
      recipients. In conclusion, long-term graft survival was superior in patients who
      never experienced acute rejection compared to those with rejection. Improvements
      in long-term graft survival can be accomplished in patients with severe rejection
      with OKT3 treatment resulting in comparable survival to those with mild
      rejection.

PMID- 8996776
TI  - Intragraft IL-4 mRNA expression is associated with down-regulation of liver graft
      rejection.
AB  - The mechanism underlying spontaneously resolving allograft rejection following
      clinical liver transplantation is unidentified. In this process, immunoregulatory
      T helper (Th)-2 cytokines like IL-4, often identified with down-regulation of the
      Th1-dependent (IL-2) cell-mediated response, might play a significant but unknown
      role. For this reason, we analyzed mRNA expression by reverse transcriptase
      polymerase chain reaction (RT-PCR) in 57 biopsies derived from 19 recipients.
      Specimens included biopsies without evidence of rejection (n = 36), biopsies with
      histological evidence of rejection (n = 10) not followed by clinical signs of
      graft rejection, and biopsies with histological rejection that were accompanied
      with clinical rejection (n = 11), defined by rising serum bilirubin and aspartate
      amino transaminase (ASAT) levels. Intragraft IL-4 mRNA expression significantly
      correlated with spontaneously resolving rejections. In 70% (7/10) of these
      biopsies, IL-4 mRNA was detectable, while only 19% (7/36) of the biopsies without
      signs of rejection (p < 0.01; Fisher's exact test) and 18% (2/11) of the
      rejection biopsies concurrent with graft dysfunction expressed the IL-4 gene (p =
      0.03). In contrast, IL-2 mRNA expression was not detectable in biopsies derived
      from the spontaneously resolving rejections. None (0/10) of these samples
      expressed the IL-2 gene, which was not significantly different from the
      proportion of biopsies transcribing the IL-2 gene in the absence of rejection
      (11%, 4/36). IL-2 mRNA expression was found more often in biopsies associated
      with graft dysfunction (36%, 4/11). These results show that IL-4, in contrast to
      IL-2 mRNA expression, is associated with spontaneously resolving liver rejection.
      This suggests that Th2 cells down-regulate the Th1-dependent cell-mediated immune
      response after clinical liver transplantation.

PMID- 8996777
TI  - Early ganciclovir therapy effectively controls viremia and avoids the need for
      cytomegalovirus (CMV) prophylaxis in renal transplant patients with
      cytomegalovirus antigenemia.
AB  - Cytomegalovirus (CMV) infection is still a problem for organ transplant
      recipients despite studies that long-term prophylaxis with high dose of acyclovir
      or ganciclovir given to all organ recipients may limit the consequences of
      infection and disease. In the present report of 160 consecutive renal transplant
      patients, we used a diagnostic assay for CMV antigenemia (detection of CMV
      antigen in peripheral blood leukocytes) and treated with ganciclovir only those
      patients who had a positive test. No patient in this series had routine
      prophylaxis. Out of 160 patients, 71 had clinical and/or laboratory signs of
      infection, and were tested for early antigen in peripheral leukocytes. The test
      was positive in 35, all of whom received a course of 3 wk ganciclovir treatment
      which effectively cured CMV in 34 count of 35. One patient was ganciclovir
      resistant, but responded to foscarnet. None of the 36 patients who had no early
      antigenemia and did not receive treatment developed the disease. The treatment
      was extremely well tolerated in all our patients with no adverse events. Thus,
      even though this was not a controlled study, our present results may be taken to
      indicate that long-term acyclovir or ganciclovir for all organ transplant
      recipients might be no longer totally justified. We conclude that detecting viral
      antigen in circulating leukocytes identifies patients who are indeed at risk of
      developing severe CMV disease. When these patients are treated early enough, CMV
      is eliminated with a relatively short course of ganciclovir, which has virtually
      no side effects.

PMID- 8996778
TI  - Effective immunization against influenza in pediatric renal transplant
      recipients.
AB  - Viral infections such as influenza are an important cause of morbidity following
      organ transplantation. We evaluated the immunogenicity of a commercially
      available influenza vaccine in pediatric renal transplant recipients in a two
      phase, prospective study. In phase one, 47 transplant patients and seven control
      subjects with bronchopulmonary dysplasia received influenza vaccine. Sera were
      collected at the time of vaccination and 6 wk later. In phase two, sera from 18
      transplant recipients and 47 healthy adults who had received the same vaccine
      were collected 6-12 months after vaccination. Antibody titers to the
      A/Taiwan/1/86 antigen were measured with hemagglutination inhibition assay in
      both phases of the study. Vaccine was well tolerated in all subjects. No
      vaccinated patient required hospitalization for complications of influenza
      infection. Vaccination did not increase the frequency of acute allograft
      rejection. In phase one, 43 patients (91%) and 5 controls (71%) either
      seroconverted (developed a fourfold or greater rise in titer), or developed post
      vaccination titers > or = 1:160 (p = NS). Among the transplant recipients, non
      seroconverters had a higher pre-vaccination geometric mean antibody titer (GMT)
      than those who seroconverted. Seroconversion developed independently of whether
      patients received double or triple immunosuppression. In phase two, post
      vaccination GMT were similar for patients and control subjects at 11.5 and 8
      months post-vaccination, respectively. In our study, influenza vaccination
      produced equivalent humoral immunity in transplant recipients and normal
      subjects. Routine influenza vaccination should be performed annually in this high
      risk population.

PMID- 8996779
TI  - Cutaneous squamous cell carcinoma metastatic to the parotid gland in a transplant
      patient.
AB  - Parotid metastases from cutaneous neoplasms are rare and have a relatively good
      prognosis if limited to the lymph nodes. When extension beyond the lymph nodes
      occurs, prognosis is grave. It has also been reported that transplant patients
      have a higher incidence of cutaneous carcinoma, which tends to be more
      aggressive. We report a case of an aggressive squamous cell carcinoma metastatic
      to the parotid gland in a liver transplant patient. The literature pertaining to
      parotid area metastasis and cancer in transplant recipients is reviewed. We
      conclude that clinicians should have a higher clinical index of suspicion for
      cutaneous lesions in transplant patients and that cutaneous lesions at risk for
      metastasis to the parotid should be treated more aggressively.

PMID- 8996780
TI  - The feasibility of HLA matching for lung transplantation.
AB  - The benefits of HLA matching have been clearly demonstrated in renal and cardiac
      transplantation. Recent studies suggest that HLA matching may be associated with
      improved survival rates for transplantation as well. However, the effect of HLA
      matching for lung transplantation has not been clearly demonstrated. Despite the
      possible benefits of HLA compatibility, matching for lung transplantation is
      based solely on ABO compatibility and lung size. Several factors limit the
      feasibility of utilizing HLA matching for lung transplantation. Among these
      factors is the time required to perform HLA typing, to identify appropriate
      recipients, and to allocate lungs; an additional constraint is the urgent need
      for transplantation in patients experiencing rapid clinical decline. The
      obstacles to using prospective HLA matching for lung allocation are significant,
      and matching lung donors and recipients according to histocompatibility status
      would require considerable effort. However, with supra-regional cooperation among
      transplant centers and procurement agencies, it appears feasible to consider HLA
      matching for lung transplantation. Given the potential for improved survival, a
      project should be undertaken to determine the impact of HLA matching on the
      outcome of lung transplantation.

PMID- 8996783
TI  - Computational analysis of transcriptional regulatory elements: a field in flux.

PMID- 8996781
TI  - Disparate changes in plasma and tissue pentosidine levels after kidney and kidney
      pancreas transplantation.
AB  - The advanced glycation end-product, pentosidine, was measured in plasma proteins
      and skin collagen before and after kidney and kidney-pancreas transplantation in
      order to determine the relationship between plasma and tissue levels and to
      characterize the pattern of change in pentosidine levels after correction of
      hyperglycemia and/or renal failure. The content of pentosidine in skin collagen
      was higher than that in plasma proteins both before and after transplantation.
      However, there was no correlation between plasma and skin pentosidine levels.
      Prior to transplantation, the content of pentosidine in skin collagen was related
      to the duration of dialytic therapy, presence of diabetes mellitus, age, and
      female gender. Following transplantation, plasma pentosidine levels were
      inversely correlated with glomerular filtration rate (r = 0.64; p < 0.01). While
      plasma pentosidine levels consistently decreased after transplantation, levels in
      skin collagen increased in 10 of 13 patients, including 5 of 6 recipients of
      kidney-pancreas transplants. Our results indicate that tissue levels of
      pentosidine persist for long periods of time after kidney or kidney-pancreas
      transplantation, despite consistent decreases in levels measured in plasma
      proteins. The observed increase in tissue pentosidine levels in a majority of
      patients suggests that formation of advanced glycation end-products may continue
      after otherwise successful kidney or kidney-pancreas transplantation.

PMID- 8996782
TI  - Type II diabetes after combined kidney and pancreas transplantation for type I
      diabetes mellitus and end-stage renal disease.
AB  - We report a case of a patient who developed type II diabetes after receiving a
      successful combined kidney and pancreas transplant for type I diabetes and end
      stage renal disease. This patient underwent a combined kidney and pancreas
      transplant and had no evidence of rejection with good function following the
      transplant for nine months. The patient developed significant post-transplant
      obesity with her transplant weight of 80 kg rising to 109 kg. At this level of
      obesity, the patient developed fasting hyperglycemia of 180 mg/dl with no change
      in her renal function or her pancreas exocrine function. She developed
      hyperinsulinemia to this fasting hyperglycemia. The clinical course of this
      patient demonstrates that rapid weight gain following transplantation can result
      in type II diabetes.

PMID- 8996784
TI  - Approaching the function of new genes by detection of their potential upstream
      activation sequences in Saccharomyces cerevisiae: application to chromosome III.
AB  - The systematic sequencing of the yeast genome reveals the presence of many
      potential genes of unknown function. One way to approach their function is to
      define which regulatory system controls their transcription. This can also be
      accomplished by the detection of an upstream activation sequence (UAS). Such a
      detection can be done by computer, provided that the definition of a UAS includes
      sufficient and precise rules. We have established such rules for the UASs of the
      GAL4, RAP1 (RPG box), GCN4, and the HAP2/HAP3/HAP4 regulatory proteins, as well
      as for a motif (PAC) frequently found upstream of the genes of the RNA polymerase
      A and C subunits. These rules were applied to the chromosome III DNA sequence,
      and gave precise predictions.

PMID- 8996785
TI  - Computation of DNA structural variability--a new predictor of DNA regulatory
      regions.
AB  - MOTIVATION: Local separation of the two strands of the DNA duplex is an essential
      step in important biological activities, including the initiation of
      transcription and replication. This conformational transition occurs in response
      to imposed stresses, which are stringently regulated in vivo. RESULTS: This paper
      describes two computational methods to analyse this phenomenon: an approximate
      statistical mechanical method and a Monte Carlo sampling technique. Analysis of
      genomic DNA sequences shows that sites of predicted duplex destabilization are
      closely associated with regions regulating transcription, with the most
      destabilized sites coinciding with 3' gene termini. Experimental results
      supporting this conclusion are described. The incorporation of this technique
      into computational searches for regulatory regions is discussed. AVAILABILITY:
      Because the programs implementing these calculations are complex to use and not
      completely developed, they have not been released yet. However, the author will
      analyze any DNA sequences upon request. Sequences may be submitted electronically
      to benham/msvax.mssm.edu.

PMID- 8996786
TI  - Applicability of the multiple alignment algorithm for detection of weak patterns:
      periodically distributed DNA pattern as a study case.
AB  - MOTIVATION: A nucleosome DNA positioning pattern is known to be one of the
      weakest (highly degenerated) patterns. The alignment procedure that has been
      developed recently for the extraction of such a pattern is based on a statistical
      matching of the sequences, and its success depends on the pattern/background
      ratio in the individual sequences and in the generated pattern. The heuristic
      nature of the method and distinctive properties of the pattern bring up the
      question of efficiency and sensitivity in the procedure. This paper presents a
      method of verification for this multiple sequence alignment algorithm. RESULTS:
      To verify the applicability of the multiple alignment approach, we constructed a
      set of sequences carrying the hidden pattern. The pattern was presented by weak
      ('signal') oscillations of occurrences of AA and TT dinucleotides along otherwise
      random sequences. Only a few dinucleotides of any given 145 base long sequence
      would correspond to the signal, appearing in about the same phase within the
      simulated periodic pattern. The novelty of our simulation approach is that we
      simulated a database as a whole, as opposed to simulating each sequence
      separately. The correlation between the hidden pattern and a sequence from the
      database is negligible on average, but our statistical multicycle alignment
      procedure produced the pattern with attributes very close to the simulated ones.
      The accuracy of the procedure was tested and calibrated. The presence in a
      typical sequence of as little as three dinucleotides corresponding to the signal
      is sufficient to generate (detect) the pattern hidden in a collection of 204
      sequences.

PMID- 8996787
TI  - The prediction of vertebrate promoter regions using differential hexamer
      frequency analysis.
AB  - MOTIVATION: To develop an algorithm utilizing differential hexamer frequency
      analysis to discriminate promoter from non-promoter regions in vertebrate DNA
      sequence, without relying upon an extensive database of known transcriptional
      elements. RESULTS: By determining hexamer frequencies derived from known promoter
      regions, coding regions and non-coding regions in vertebrates' DNA sequence, and
      a formula first applied by Claverie and Bougueleret (1986), a discriminant
      measure was created that compares promoter regions with coding (D1) and non
      coding (D2) sequence. The algorithm is able to identify correctly the promoter
      regions in 18 of 29 loci (62.1%) from an independent test data set. With program
      options set to identify only one promoter region in the forward strand, there are
      11 false-positive predictions in 208 714 nucleotides (one false positive in 18
      974 single-stranded bp). With options set to analyze sequence in discrete
      segments, there is no appreciable improvement in sensitivity, whereas the
      specificity falls off predictably. It is of particular interest than a search for
      a peak score (independent of an absolute threshold) is more accurate that a
      search based upon a fixed scoring threshold. This suggests that the selection of
      promoter sites may be influenced by the global properties of an entire sequence
      domain, rather than exclusively upon local characteristics.

PMID- 8996788
TI  - Hamming-Clustering method for signals prediction in 5' and 3' regions of
      eukaryotic genes.
AB  - MOTIVATION: Gene expression is regulated by different kinds of short nucleotide
      domains. These features can either activate or terminate the transcription
      process. To predict the signal sites in the 5' and 3' gene regions we applied the
      Hamming-Clustering network (HC) to the TATA box, to the transcription initiation
      site and to the poly(A) signal determination in DNA sequences. This approach
      employs a technique deriving from the synthesis of digital networks in order to
      generate prototypes, or rules, which can be directly analysed or used for the
      construction of a final neural network. RESULTS: More than 1000 poly-A signals
      have been extracted from EMBL database rel. 42 and used to build the training and
      the test set. A full set of the eukaryotic genes (1252 entry) from the Eukaryotic
      Promoter Database (EPD rel. 42) have been used for the TATA-box signal and
      transcription network approach. The results show the applicability of the Hamming
      Clustering method to functional signal prediction.

PMID- 8996789
TI  - GenomeInspector: a new approach to detect correlation patterns of elements on
      genomic sequences.
AB  - MOTIVATION: Most of the sequences determined in current genome sequencing
      projects remain at least partially unannotated. The available software for DNA
      sequence analysis is usually limited to the prediction of individual elements
      (level 1 methods), but does not assess the context of different motifs. However,
      the functionality of biological units like promoters depends on the correct
      spatial organization of multiple individual elements. RESULTS: Here, we present a
      second-level software package called GenomeInspector
      [[http:@www.gsf.de/biodv/genomeinspector.html ]], for further analysis of results
      obtained with level 1 methods (e.g. MatInspector
      [[http:@www.gsf.de/biodv/matinspector.html ]] or ConsInspector
      [[http:@www.gsf.de/biodv/consinspector.html++ +]]). One of the main features of
      this modular program is its ability to assess distance correlations between large
      sets of sequence elements which can be used for the identification and definition
      of basic patterns of functional units. The program provides an easy-to-use
      graphical user interface with direct comprehensive display of all results for
      megabase sequences. Sequence elements showing spatial correlations can be easily
      extracted and traced back to the nucleotide sequence with the program.
      GenomeInspector identified promoters of glycolytic enzymes in yeast
      [[http:@www.mips.biochem.mpg.de/mips/yeast/]] as members of a subgroup with
      unusual location of an ABF1 site. Solely on the basis of distance correlation
      analysis, the program correctly selected those transcription factors within these
      promoters already known to be involved in the regulation of glycolytic enzymes,
      demonstrating the power of this method.

PMID- 8996790
TI  - Syntactic recognition of regulatory regions in Escherichia coli.
AB  - MOTIVATION: One of the most common methodologies to identify cis-regulatory sites
      in regulatory regions in the DNA is that of weight matrices, as testified by
      several articles in this issue. An alternative to strengthen the computational
      predictions in regulatory regions is to develop methods that incorporate more
      biological properties present in such DNA regions. The grammatical implementation
      presented in this paper provides a concrete example in this direction. RESULTS:
      On the basis of the analysis of an exhaustive collection of regulatory regions in
      Escherichia coli, a grammatical model for the regulatory regions of sigma 70
      promoters has been developed. The terminal symbols of the grammar represent
      individual sites for the binding of activator and repressor proteins, and include
      the precise position of sites in relation to transcription initiation. Combining
      these symbols, the grammar generates a large number of different sentences, each
      of which can be searched for matching against a collection of regulatory regions
      by means of weight matrices specific for each set of sites for individual
      proteins. On the basis of this grammatical model, a Prolog syntactic recognizer
      is presented here. Specific subgrammars for ArgR, LexA and TyrR were implemented.
      When parsing a collection of 128 sigma 70 promoter regions, the syntactic
      recognizer produces a much lower number of false-positive sites than the standard
      search using weight matrices.

PMID- 8996791
TI  - Interfering contexts of regulatory sequence elements.
AB  - MOTIVATION: Although one would normally expect a given regulatory element to
      perform best when it fully matches its consensus sequence, this is generally far
      from being the case. Usually, almost none of the actual sites fits the consensus
      exactly, and some of those that do fit do not perform well. The main reason for
      that is the very nature of the sequences and the messages (codes) they contain.
      Normally, any given stretch of the sequence with one or another regulatory site
      not only carries this regulatory message, but several more messages of various
      types as well. These messages overlap with the regulatory element in such a way
      that the letter (base) which actually appears in any given sequence position
      simultaneously belongs to one or more additional codes. Apart from numerous
      individual codes (sequence patterns) specific for a given species or gene, there
      are many different general (universal) sequence codes all interacting with one
      another. These are the classical triplet code, DNA shape code, chromatin code,
      gene splicing code, modulation code and many more, including those that have not
      yet been discovered. Examples of overlapping of different codes and their
      interaction are discussed, as well as the role of degeneracy of the codes and the
      sequence complexity as a function of code density.

PMID- 8996792
TI  - The statistical significance of nucleotide position-weight matrix matches.
AB  - MOTIVATION: To improve the detection of nucleotide sequence signals (e.g.
      promoter elements) by position-weight matrices (PWM) using the concept of
      statistically significant matches. RESULTS: The Mksite program was originally
      developed for analyzing protein sequences. We report NMksite, a new version
      adapted to the processing of nucleotide sequences. NMksite creates PWM from
      nucleotide sequence block alignments or occurrence tables using three weight
      computation schemes. An original feature of NMksite is the numerical computation
      of the statistical significance of PWM matches. The utility of this concept is
      demonstrated in the context of the prediction of splice sites and promoter
      regions.

PMID- 8996793
TI  - Combining structural analysis of DNA with search routines for the detection of
      transcription regulatory elements.
AB  - MOTIVATION: Analysis of unannotated genomic sequences for regulatory regions
      depends on a reliable recognition of individual cis-acting elements. Since some
      of them have a very low conserved sequence pattern, additional criteria are
      required. RESULTS: Using molecular modelling techniques, we have created a
      complete database for the conversion of base sequences into profiles of
      structural parameters of DNA. On this basis, search routines can be developed
      that scan for profile matches. They may be used instead of or, probably most
      appropriate in most cases, in combination with conventional sequence pattern
      searches.

PMID- 8996794
TI  - Long-term treatment with some methylxanthines decreases the susceptibility to
      bicuculline- and pentylenetetrazol-induced seizures in mice. Relationship to c
      fos expression and receptor binding.
AB  - The effects of long-term oral administration of low doses of caffeine (0.3 g/l)
      and its metabolites theophylline, theobromine and paraxanthine (each at 0.5 g/l
      in drinking water) on bicuculline- and pentylenetetrazol (PTZ)-induced seizures
      and c-fos expression were studied in mice. In addition, adenosine and
      benzodiazepine receptor density was examined. The plasma levels of the
      methylxanthines were much higher during the active period at night than during
      the day. The maximal level of caffeine was 14 microM. Brain theophylline levels
      (8-13 nmol/g) tended to be higher and more constant than brain caffeine levels in
      caffeine-consuming mice. Clonic seizures induced by bicuculline (4 mg/kg i.p.)
      were significantly reduced in severity by 14 day caffeine treatment and mortality
      was also reduced. Long-term treatment with caffeine metabolites was less
      effective. The seizures induced by PTZ (60 mg/kg i.p.) were also significantly
      reduced by long-term caffeine treatment. After bicuculline or PTZ treatment, c
      fos mRNA expression was weaker in the cerebral cortex in animals receiving
      caffeine, irrespective of whether the animals had seizures or not. No significant
      changes in the binding of adenosine receptor ligands or benzodiazepines were seen
      after long-term caffeine treatment. These results show that long-term treatment
      with caffeine in a dose that is commonly seen in humans decreases the seizures
      induced by bicuculline, and to a lesser extent, those induced by PTZ. This may be
      related to a decreased neuronal excitability. The effect is due to the combined
      effects of theophylline, to which caffeine is metabolized in brain, and caffeine
      itself, but could not be ascribed to changes in A1 and A2A adenosine or
      benzodiazepine receptors.

PMID- 8996795
TI  - The influence of nitric oxide on perigeniculate GABAergic cell activity in the
      anaesthetized cat.
AB  - We have tested the effect of iontophoretic application of the nitric oxide
      synthase inhibitor L-nitroarginine on the activity of a population of 53
      perigeniculate (PGN) cells, recorded extracellularly in the anaesthetized
      paralysed cat. In all cells tested with visual stimulation during L-nitroarginine
      application (n = 15), the visually elicited responses were markedly reduced, on
      average by 63 +/- 15%, and there was a reduction in spontaneous activity too.
      This effect was blocked by co-application of the substrate for nitric oxide
      synthase, L-arginine, but not by the inactive D-isoform, although application of
      L-arginine alone was without effect. Pressure application of the nitric oxide
      donor S-nitroso-N-acetylpenicillamine (SNAP) elevated both visual responses and
      spontaneous discharge, an effect also seen with a second nitric oxide donor,
      sodium nitroprusside (n = 12). The nitric oxide synthase inhibitor L
      nitroarginine was applied to a sub-population of seven cells and it selectively
      decreased NMDA mediated excitation (reduction 80 +/- 14%) with little or no
      effect on the excitation mediated by alpha-amino-3-hydroxy-5-5-methyl-4-isoxazole
      propionic acid (AMPA) or quisqualate (effects not statistically significant), and
      it had no effect (n = 7) on excitation mediated by the metabotropic agonist
      (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). Furthermore,
      application of SNAP also increased the magnitude of excitatory responses mediated
      by NMDA receptors. On a different population of seven cells, application of the
      new NO donor diethylamine-nitric oxide (DEA-NO) enhanced the actions of NMDA
      without an effect on responses to AMPA. These effects are qualitatively and
      quantitatively similar to those we have previously described for X and Y type
      cells in the dorsal lateral geniculate nucleus (dLGN), despite the known opposite
      effects of acetylcholine (ACh) application in the dLGN and PGN (ACh is co
      localized with nitric oxide synthase at both sites). We propose that within the
      PGN nitric oxide acts to enhance transmission utilizing NMDA receptors
      selectively (thereby interacting with the globally inhibiting effect of ACh at
      this site) to enhance visual responses, reducing or removing the non-specific
      inhibitory drive from PGN to dLGN seen in the spindling activity of slow-wave
      sleep. These effects will act in concert with the facilitatory actions of both
      ACh and nitric oxide within the dLGN proper, and will thereby enhance the
      faithful transmission of visual information from retina to cortex.

PMID- 8996796
TI  - Structural analysis of the murine cell adhesion molecule L1 by electron
      microscopy and computer-assisted modelling.
AB  - In the present study we have analysed the morphology of two fragments with
      apparent molecular weights of 180 and 140 kDA (L1-180 and L1-140) derived from
      the extracellular region of the murine neural cell adhesion molecule L1. The
      fragment L1-180 consists of almost the entire extracellular part of the molecule,
      and is built up of six immunoglobulin-like and five fibronectin type III-like
      domains. Fragment L1-140 lacks one-half of the third, the fourth and the fifth
      fibronectin type III-like domains. By electron microscopic analysis of rotary
      shadowed molecules, L1-140 and L1-180 revealed fibrillar structures 31-43 nm long
      and 7-12 nm wide with one pronounced globular terminal domain. As determined by
      complex formation with an L1 antibody, this terminal part of the molecule is
      formed by the fibronectin type III-like domains. The individual structures showed
      variation and complexity, and four distinct aspects were identified. These
      different forms probably represent two-dimensional projections of the same three
      dimensional helical structure. Computer-assisted modelling of the L1 molecule,
      i.e. the protein backbone, showed no strong intramolecular interaction between
      the different fibronectin type III- or Ig-like domains, suggesting that the
      formation of the globular part of the molecule is probably achieved by protein
      carbohydrate and/or carbohydrate-carbohydrates rather than protein-protein
      interactions. In addition, our model proposes that interactions occur within the
      interfaces between the different domains. The highly conserved amino acid
      residues in these regions point to the necessity of maintaining the orientation
      between the different domains.

PMID- 8996798
TI  - GABA and glycine in synaptic glomeruli of the rat spinal dorsal horn.
AB  - The superficial dorsal horn of rat spinal cord contains two types of synaptic
      glomerulus, which are centred around the terminals of unmyelinated and myelinated
      primary afferents respectively. Both types of glomerulus contain GABAergic axons
      and dendrites, which are thought to originate from local inhibitory interneurons.
      Some of the dendrites contain synaptic vesicles, and may be presynaptic to the
      central axon of dendroaxonic synapses. In order to determine whether GABAergic
      structures in the two types of glomerulus are derived from different populations
      of interneurons, a quantitative post-embedding immunogold study of GABA- and
      glycine-immunoreactivity in a rat dorsal horn was performed. In type I glomeruli,
      all of the peripheral axons and most vesicle-containing dendrites were GABA
      immunoreactive, but only one of 32 axons and none of the vesicle-containing
      dendrites was glycine-immunoreactive. In contrast, most of the peripheral axons
      and some of the vesicle-containing dendrites in type II glomeruli possessed both
      GABA- and glycine-immunoreactivity. This strongly suggests that different types
      of inhibitory interneuron in the dorsal horn are associated with the two types of
      glomerulus. It is therefore likely that different populations of interneurons
      mediate presynaptic inhibition of unmyelinated and myelinated primary afferents.

PMID- 8996797
TI  - Regulation of VIP and other neuropeptides by c-Jun in sensory neurons:
      implications for the neuropeptide response to axotomy.
AB  - Peripheral axotomy of adult rat sensory neurons causes induction of the
      transcription factor c-Jun and increased expression of the neuropeptides
      vasoactive intestinal polypeptide (VIP), galanin and neuropeptide Y. To determine
      whether VIP induction is dependent on transcriptional regulation by c-Jun, we
      exploited the fact that c-Jun and VIP are also induced in cultured sensory
      neurons. We blocked c-Jun synthesis by microinjecting antisense oligonucleotides
      and found that VIP expression, determined by quantitative immunofluorescence, was
      specifically reduced. Blockade of c-June expression also resulted in reduced
      neuropeptide Y expression but left galanin, substance P and calcitonin gene
      related peptide unaffected. Since in vitro electrophoretic mobility shift assays
      showed that a nominal cyclic AMP responsive element (CRE) associated with the rat
      VIP gene could bind c-Jun-containing transcription factor complexes, we next
      investigated whether VIP expression in sensory neurons might depend on
      transcription factor binding to the CRE. When a DNA plasmid containing multiple
      copies of the CRE was injected into newly cultured sensory neurons to sequester
      transcription factors binding the endogenous CRE, there was a selective reduction
      in VIP expression. VIP induction in sensory neurons therefore probably results
      from transcriptional activation by c-Jun acting in combination with other
      factor(s), possibly acting through the CRE. These results show that c-Jun can
      regulate transcription of other genes affected by axotomy and imply that it could
      be a key regulator of the neuronal axotomy response.

PMID- 8996799
TI  - Developmental expression and self-regulation of Ca2+ entry via AMPA/KA receptors
      in the embryonic chick retina.
AB  - Excessive activation of glutamate receptors in the late embryonic and adult
      retina leads to excitotoxic cell death through an increase in intracellular
      calcium concentration. Here we use the cobalt-staining technique of Pruss et al.
      to investigate the developmental expression of Ca(2+)-permeable alpha-amino-3
      hydroxy-5-methyl-isoxazole-4-propionic acid/kainate (AMPA/KA) receptors in the
      embryonic chick retina, and the effects of AMPA/KA receptor activation on cell
      survival and AMPA/KA receptor expression. Ca(2+)-permeable AMPA/KA receptors are
      present in the retina as early as embryonic day 6 (E6). While sustained
      activation of these receptors with KA led to massive cell death in explant and
      dissociated cultures of the chick retina late in development, continuous
      application of high doses of KA from early times was not excitotoxic. Cell
      survival in KA is correlated with both a reduction in cobalt staining and the KA
      evoked membrane current, and thus with a reduction in the Ca2+ entry into cells
      via AMPA/KA receptors. The effects of KA could be blocked by the non-N-methyl-D
      aspartic acid (NMDA) receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione
      (CNQX), but not by the NMDA receptor antagonist D-2-amino-5-phosphonovalerate
      (AP5) nor the L-type Ca2+ channel blockers diltiazem and nifedipine. The action
      of AP5 was mimicked by exposure to glutamate but not by the metabotropic receptor
      agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid. Thus exposure of retinal
      neurons to glutamate early in development may protect them from its excitotoxic
      actions later on.

PMID- 8996800
TI  - DA uptake sites, D1 and D2 receptors, D2 and preproenkephalin mRNAs and Fos
      immunoreactivity in rat striatal subregions after partial dopaminergic
      degeneration.
AB  - Stereotaxic injection of a limited amount of 6-hydroxydopamine in the lateral
      part of the rat substantia nigra induces a partial degeneration of the
      nigrostriatal dopaminergic system. This animal model in which the destruction of
      the dopaminergic nigral cell population reaches approximately 50% could be
      considered as a preclinical Parkinson's model. Autoradiography of dopaminergic
      uptake sites performed with a specific marker ([3H]GBR 12935) allowed the precise
      determination of dopaminergic denervated and non-denervated areas in the striatum
      1 month after partial lesion of the substantia nigra pars compacta. In both
      striatal areas, dopaminergic D1 and D2 receptor densities and dopaminergic D2 and
      preproenkephalin mRNAs levels were measured by autoradiography and in situ
      hybridization coupled to an image analysis system. Our results show that in the
      denervated striatal subregion, none of the dopaminergic targets were modified,
      contrary to the observations made after complete lesion of the nigrostriatal DA
      system at the same post-lesion delay. However, striatal Fos activation induced by
      amphetamine (5 mg/kg i.p., 2 h before killing) revealed that the number of Fos
      positive cells detected in the denervated striatal subregion was lower than that
      observed in the non-denervated one. These data argue in favour of the existence
      of compensatory mechanisms different from the up-regulation of DA receptor
      densities, thereby allowing the maintenance of striatal dopaminergic
      transmission. Such mechanisms could contribute to the delay of the appearance of
      neurological symptoms (which are reported to be clinically apparent only when
      depletion of striatal dopamine levels reaches near 80%) in Parkinsonian patients.

PMID- 8996801
TI  - Phenotype of striatal cells expressing c-Fos following amphetamine treatment of
      rats with intrastriatal dopaminergic grafts.
AB  - Activation of the nigrostriatal dopaminergic system by psychostimulants such as
      amphetamine increases c-Fos expression in the striatum, mostly in the
      striatonigral substance P-ergic pathway. This effect is greatly reduced in the
      neostriatum deprived of dopaminergic afferents. Dopaminergic grafts implanted
      into the denervated neostriatum restore the reactivity of the striatum to
      amphetamine. However, the number of striatal neurons expressing c-Fos is greatly
      increased in the graft-bearing striatum compared with the normal striatum. We
      examined whether this increase in the number of c-Fos-expressing neurons
      corresponds to the recruitment of a new neuron population, or whether it reflects
      an increase in the proportion of substance P-ergic neurons exhibiting activation
      of c-Fos. Adult rats received a unilateral 6-hydroxydopamine lesion of the
      ascending dopaminergic mesotelencephalic pathway, and a suspension of embryonic
      mesencephalic neurons was subsequently implanted into the denervated neostriatum.
      Three months after implantation, animals were injected with d-amphetamine (5
      mg/kg) and killed 2 h later. In the first experiment, striatal sections were
      processed to visualize both c-Fos protein, by immunohistochemistry, and
      preproenkephalin A or substance P, by in situ hybridization. In the second
      experiment, c-Fos and neuropeptide Y were visualized on the same sections. In
      addition, some sections incubated with anti-c-Fos antibody were counterstained
      with toluidine blue in order to determine whether cholinergic neurons were
      expressing c-Fos following amphetamine treatment. The density of neurons
      expressing c-Fos following amphetamine treatment was three-fold higher in the
      graft-bearing striata than in the striata of control animals. Approximately 75%
      of the c-Fos expressing cells were substance P-ergic in control animals whereas
      6% were enkephalinergic and only a few were neuropeptide Y-ergic or cholinergic.
      Similar proportions were found in the graft-bearing striatum, signifying that the
      pattern of activation of c-fos following amphetamine administration is not
      changed by the graft. Thus, the increased expression of c-Fos predominantly
      reflects a graft-induced increase in the proportion of neurons expressing c-Fos
      within the same population of neurons which normally expresses c-Fos in the
      striatum, i.e. the striatonigral substance P-ergic neurons; there is no
      recruitment of a new neuronal population. This increased activation of the
      striatonigral substance P-ergic pathway may underlie the abnormal behavioural
      reactions brought about by amphetamine-induced stimulation of the implanted
      dopaminergic neurons.

PMID- 8996802
TI  - Synapsin-like molecules in Aplysia punctata and Helix pomatia: identification and
      distribution in the nervous system and during the formation of synaptic contacts
      in vitro.
AB  - The distribution and biochemical features of the synapsin-like peptides
      recognized in Aplysia and Helix by various antibodies directed against mammalian
      synapsins were studied. The peptides can be extracted at low pH and are digested
      by collagenase; further, they can be phosphorylated by both protein kinase A and
      Ca2+/calmodulin-dependent protein kinase II. In the ganglia of both snails, they
      are associated with the soma of most neurons and with the neuropil; punctate
      immunostaining is present along the neurites. Using cocultures of a Helix
      serotoninergic neuron and of its target cell, we analysed the redistribution of
      the synapsin-like peptides during the formation of active synaptic contacts. When
      the presynaptic neuron is plated in isolation, both synapsin and serotonin
      immunoreactivities are restricted to the distal axonal segments and to the growth
      cones; in the presence of the target, the formation of a chemical connection is
      accompanied by redistribution of the synapsin and serotonin immunoreactivities
      that concentrate in highly fluorescent round spots scattered along the newly
      grown neurites located close to the target cell. Almost every spot that is
      stained for serotonin is also positive for synapsin. In the presynaptic cell
      plated alone, the number of these varicosity-like structures is substantially
      stable throughout the whole period; by contrast, when the presynaptic cell
      synapses the target, their number increases progressively parallel to the
      increase in the mean amplitude of cumulative excitatory postsynaptic potentials
      recorded at the same times. The data indicate that mollusc synapsin-like peptides
      to some extent resemble their mammalian homologues, although they are not
      exclusively localized in nerve terminals and their expression strongly correlates
      with the formation of active synaptic contacts.

PMID- 8996803
TI  - Differential distribution of syntaxin isoforms 1A and 1B in the rat central
      nervous system.
AB  - Syntaxin 1 binds to several proteins of the synaptic terminal and is a central
      component in the pathway of protein-protein interactions that underlies docking
      and fusion of synaptic vesicles. Molecular studies revealed the occurrence of two
      isoforms, syntaxin 1A and syntaxin 1B, which coexpress in neural tissues.
      However, they display differential expression patterns in endocrine cell types.
      We generated isoform-specific antibodies that were used in Western blotting and
      immunocytochemical studies. First, we confirmed the sole presence of syntaxin 1A
      in endocrine pituitary cells. Second, we found distinctive immunolabelling
      patterns of each isoform in the rat olfactory system, hippocampus, striatum,
      thalamus and spinal cord. In addition, the principal white matter commissures
      displayed distinct immunoreactivity for each isoform. This report shows, for the
      first time, major differences between the distributions of syntaxin 1A and
      syntaxin 1B isoforms in the rat central nervous system.

PMID- 8996804
TI  - Biphasic response of spinal GABAergic neurons after a lumbar rhizotomy in the
      adult rat.
AB  - The expression of gamma-aminobutyric acid (GABA) and of the isoforms of the
      enzyme involved in its synthesis, glutamic acid decarboxylase (GAD), is modified
      in several rat brain structures in different injury models. The aim of the
      present work was to determine whether such plasticity of the GABAergic system
      also occurred in the deafferented adult rat spinal cord, a model where a major
      reorganization of neural circuits takes place. GABAergic expression following
      unilateral dorsal rhizotomy was studied by means of non-radioactive in situ
      hybridization to detect GAD67 mRNA and by immunohistochemistry to detect GAD67
      protein and GABA. Three days following rhizotomy the number of GAD67 mRNA
      expressing neurons was decreased in the superficial layers of the deafferented
      horn, while GABA immunostaining of axonal fibres located in this region was
      highly increased. Seven days after lesion, on the other hand, many GAD67 mRNA
      expression neurons were bilaterally detected in deep dorsal and ventral layers,
      this expression being correlated with the increased detection of GAD67
      immunostained somata and with the reduction of GABA immunostaining of axons. GABA
      immunostaining was frequently found to be associated with reactive astrocytes
      that exhibited intense immunostaining for glial fibrillary acidic protein (GFAP)
      but remained GAD67 negative. These results indicate that degeneration of afferent
      terminals induces a biphasic response of GABAergic spinal neurons located in the
      dorsal horn and show that many spinal neurons located in deeper regions re
      express GAD67, suggesting a possible participation of the local GABAergic system
      in the reorganization of disturbed spinal networks.

PMID- 8996805
TI  - Identification of a determinant of acetylcholine receptor gating kinetics in the
      extracellular portion of the gamma subunit.
AB  - A large body of structure-function studies has identified many of the functional
      motifs underlying ion permeation through acetylcholine receptor (AChR) channels.
      The structural basis of channel gating kinetics is, however, incompletely
      understood. We have previously identified a novel shorter form of the AChR gamma
      subunit, which lacks the 52 amino acids within the extracellular amino-terminal
      half, encoded by exon 5. To define the contribution of the missing domain to AChR
      channel function, we have transiently coexpressed the mouse short gamma subunit
      [gamma(s)] with alpha, beta and delta subunits in human cells and recorded single
      channel currents from the resulting AChRs. Our findings show that replacement of
      the gamma by the gamma(s) subunit confers a long duration characteristic to AChR
      channel openings without altering unitary conductance sizes or receptor affinity
      for the transmitter. We also show that alpha beta gamma(s) delta AChR channels
      exhibit a peculiar voltage sensitivity characterized by a short opening duration
      when the membrane potential is hyperpolarized. Together, these findings indicate
      that the domain in the extracellular amino-terminal half of the gamma subunit
      that encompasses a conserved disulphide loop and a critical tyrosine residue
      implicated in receptor oligomerization and insertion at the cell surface is a
      functional motif that also modulates AChR channel gating kinetics. The results
      also provide a molecular explanation of the functional diversity exhibited by
      skeletal muscle AChRs during development.

PMID- 8996806
TI  - Effects of high helium pressure on intracellular and field potential responses in
      the CA1 region of the in vitro rat hippocampus.
AB  - We have investigated the effects of high helium pressure (up to 13.3 MPa) on the
      electrophysiological responses of CA1 neurons in rat hippocampal slices using a
      purpose built pressure chamber, designed to facilitate field potential and
      intracellular recording. In field potential experiments, near threshold
      orthodromic responses were depressed by modest pressure (0.4 MPa). At higher
      stimulus intensities, orthodromic and antidromic population spike amplitudes were
      not increased at 5 MPa but were significantly enhanced at 10 MPa, and multiple
      population spikes were observed in some experiments. Orthodromic paired pulse
      potentiation was not affected by pressure up to 10 MPa. In intracellular
      experiments there were no significant differences between mean values obtained
      for resting membrane potential and input resistance at atmospheric pressure and
      pressures of up to 10 MPa. However, spontaneous depolarizing membrane potential
      excursions, decreased slow after-hyperpolarization responses and reduced
      accommodation properties were observed at pressure (5-10 MPa). One possibility is
      that the SK and M potassium channel systems may be more sensitive to high
      pressure than other membrane ion channels. These effects may contribute towards
      the high pressure neurological syndrome observed in vivo.

PMID- 8996807
TI  - Neuronal control of MHC class II inducibility in rat astrocytes and microglia.
AB  - We analysed the inducibility of major histocompatibility complex (MHC) class II
      molecules of astrocytes and microglia in organotypic hippocampus slice cultures
      of Lewis rats. Treatment with interferon-gamma (IFN-gamma) resulted in the
      induction of MHC class II molecules on microglia preferentially in the injured
      marginal zones of the slice culture, but only sporadically in areas containing
      intact neuronal architecture. In astrocytes, inducibility of MHC class II
      molecules was even more strictly controlled. IFN-gamma treatment induced MHC
      class II expression only in the slice culture zones containing degenerated
      neurons, and not in the presence of functional neurons. After suppression of
      spontaneous neuronal activity of the slice culture by the sodium channel blocker
      tetrodotoxin, MHC class II molecules on astrocytes could be induced by IFN-gamma
      in areas with intact neuronal architecture, and microglia cells exhibited a
      higher level of expression. These data suggest that loss of neurons could result
      in MHC class II inducibility of glial cells, and thus in increased immune
      reactivity of nervous tissue.

PMID- 8996808
TI  - Lesion study of the distribution of serotonin 5-HT4 receptors in rat basal
      ganglia and hippocampus.
AB  - The regional distribution of 5-hydroxytryptamine (5-HT4) receptors labelled with
      [3H]GR113808 was examined in rat basal ganglia and hippocampus after specific
      lesions. Lesion of serotonin neurons induced by injections of 5,7
      dihydroxytryptamine into the dorsal and medial raphe nuclei resulted in increased
      5-HT4 receptor binding in most regions examined, compared with controls. More
      precisely, there was a 78% increase in the rostral but no change in the caudal
      part of caudate-putamen, and 83% and 54% increases in the shell and core of the
      nucleus accumbens respectively. In the substantia nigra, the increase in 5-HT4
      binding was larger (72%) than that in the globus pallidus (32%). In the
      hippocampus, 63%, 30% and 28% increases were measured in CA2, CA1 and CA3
      respectively. Following lesion of dopamine neurons by intranigral injection of 6
      hydroxydopamine, increased 5-HT4 receptor binding was observed in the caudal
      (59%), but not the rostral part of caudate-putamen, as well as in the globus
      pallidus (93%). Since no decreases in 5-HT4 receptor density were detected after
      the dopamine lesion, it was concluded that these receptors are not expressed in
      dopamine neurons. Kainic acid lesions of the caudate-putamen were associated with
      dramatic local decreases in 5-HT4 receptor binding on the injected side (-89%),
      which suggested that striatal neurons express 5-HT4 receptors. Corresponding
      decreases of 72 and 20% in receptor density were detected in globus pallidus and
      substantia nigra, consistent with a presumed localization of 5-HT4 receptors on
      striatal GABA neurons projecting to these regions. In the substantia nigra, the
      decrease in [3H]GR113808 binding was localized to the pars lateralis, indicating
      that striatal neurons belonging to the cortico-striato-nigro-tectal pathway, and
      containing GABA and dynorphin, express 5-HT4 receptors.

PMID- 8996809
TI  - Phenylglycines can evoke quisqualate-primed depolarizations in rat cingulate
      cortex: an effect associated with [3H]DL-AP4 uptake.
AB  - Depolarization could be evoked in slices of rat cingulate cortex by the normally
      non-excitatory compound L-2-amino-4-phosphonobutyrate (L-AP4) if the slices had
      been sensitized by exposure to quisqualate. The magnitude of the response to L
      AP4 was dependent on the concentrations of both L-AP4 and quisqualate and was
      inhibited by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor
      antagonism. A series of phenylglycine analogues were capable of evoking similar
      dose-dependent depolarizations in the rat cingulate cortex following quisqualate
      sensitization, the most potent being (S)-4-carboxy-3-hydroxyphenylglycine. If the
      superfusate collected during application of (S)-4-carboxy-3-hydroxyphenylglycine
      to a quisqualate-sensitized slice was administered to a slice not previously
      exposed to quisqualate, a small depolarization was obtained. All the compounds
      shown to be capable of evoking the quisqualate-sensitized response showed
      affinity for the L-AP4 uptake site whilst having no affinity at ionotropic
      glutamate receptors and different profiles of activity at metabotropic glutamate
      receptors. None of the compounds was active at the metabotropic glutamate 4a
      receptor. There was a statistically significant correlation between a compound's
      effectiveness in inhibiting [3H]DL-AP4 uptake into rat cortical synaptosomes and
      its potency in evoking quisqualate-sensitized depolarization. It is concluded
      that this response may be the result of hetero-exchange between L-AP4 ligands and
      quisqualate.

PMID- 8996810
TI  - 7-OH-DPAT differentially reverses clozapine- and haloperidol-induced increases in
      Fos-like immunoreactivity in the rodent forebrain.
AB  - The pattern of neurons which display haloperidol-induced Fos-like
      immunoreactivity closely matches the distribution of striatal D2 dopamine
      receptors, whereas clozapine-induced Fos-like immunoreactivity occurs primarily
      in regions that contain high levels of the D3 dopamine receptor. These
      neuroanatomical correlations suggest that haloperidol and clozapine may elevate
      Fos-like immunoreactivity by blocking D2 and D3 receptors respectively. In order
      to test this hypothesis, the abilities of prior administration of the D3 receptor
      preferring agonist 7-hydroxy-N,N'-di-n-propyl-2-aminotetraline (7-OH-DPAT) to
      competitively reverse haloperidol- and clozapine-induced increases in Fos-like
      immunoreactivity were compared. Administration of 7-OH-DPAT (0.05 mg/kg, s.c.) 30
      min before clozapine (20 mg/kg, s.c.) produced a 60% reduction in the number of
      neurons that displayed clozapine-induced Fos-like immunoreactivity in the major
      island of Calleja, nucleus accumbens and medial aspect of the striatum, while
      prior administration of 0.5 mg/kg (s.c.) of 7-OH-DPAT completely reversed these
      increases in Fos-like immunoreactivity. In contrast, the increases in Fos-like
      immunoreactivity in the major island of Calleja, nucleus accumbens and striatum
      (medial and dorsal aspects) induced by haloperidol (0.1 mg/kg, s.c.) were only
      reduced by the high dose of 7-OH-DPAT (0.5 mg/kg, s.c.). Hence, clozapine-induced
      increases in Fos-like immunoreactivity were more readily reversed by 7-OH-DPAT
      than elevations in Fos-like immunoreactivity produced by haloperidol. These
      results suggest that D3 receptor blockade plays a larger role in mediating
      clozapine- than haloperidol-induced increases in Fos-like immunoreactivity.

PMID- 8996811
TI  - Induction of Stat3, a signal transducer and transcription factor, in reactive
      microglia following transient focal cerebral ischaemia.
AB  - Stat3, a member of the family of cytoplasmic signal transducers and activators of
      transcription, was found in the rat brain in vivo under physiological conditions
      and was stimulated following transient focal cerebral ischaemia. A transient
      episode of middle cerebral artery occlusion induced a strong microglial response
      in the areas undergoing neural cell death from 4 days after middle cerebral
      artery occlusion. This was accompanied by increased expression of Stat3 in the
      ipsilateral cortex and striatum, as revealed by Western blotting of tissue
      extracts. Immunohistochemistry showed strong induction of Stat3 in reactive
      microglial cells 4, 7 and 15 days after cerebral ischaemia. Stat3 was seen in the
      microglia cytoplasm, but in many microglial cells immunoreactivity was also
      distributed within the nucleus. These results suggest that Stat3 mediates signal
      transduction and activates transcription in reactive microglia in vivo following
      brain ischaemia.

PMID- 8996812
TI  - NMDA and kainate-evoked release of nitric oxide and classical transmitters in the
      rat striatum: in vivo evidence that nitric oxide may play a neuroprotective role.
AB  - The effects of N-methyl-D-aspartate (NMDA), kainate, S-alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionate (AMPA) and KCl on striatal nitric oxide (NO),
      acetylcholine (ACh), dopamine (DA), serotonin (5-HT), aspartate (ASP), glutamate
      (GLU) and gamma-aminobutyric acid (GABA) release were measured in anaesthetized
      rats in vivo by microdialysis and in vitro in organotypic slice cultures. Local
      NMDA (1-100 microM) infusion by retrodialysis dose-dependently increased levels
      of classical transmitters, NO2-, NO3-, citrulline and arginine at similar
      thresholds (10 microM). Similar patterns of NMDA-evoked (50 microM) release were
      seen in striatal cultures. NMDA-evoked changes were all calcium-dependent and
      blocked by NMDA (APV or MK-801) but not AMPA/kainate (DNQX) receptor antagonists,
      excepting DA which could be prevented by both. In vivo, kainate increased NO2-,
      NO3-, CIT and ARG levels at 50 and 100 microM but was less potent than NMDA.
      Kainate also evoked significant ACh, DA and GLU release dose-dependently starting
      at 1-10 microM whereas 5-HT, ASP and GABA required 50 or 100 microM doses.
      Kainate effects were inhibited by DNQX, but not by APV, and were calcium
      dependent, AMPA failed to alter NO2-, NO3-, CIT or ARG levels at 50 or 100 microM
      doses but dose-dependently increased ACh and DA. Similar results were seen with
      kainate (50 microM) and AMPA (50 microM) in vitro. KCl evoked NO2-, NO3-, CIT and
      ARG release as well as that of the classical transmitters in vivo and in vitro.
      In vivo administration of the NO synthase inhibitor L-nitroarginine (L-NARG; 100
      microM) significantly reduced NO2-, NO3- and CIT levels and prevented NMDA,
      kainate or KCl-evoked increases. It also potentiated ACh, ASP, GLU and GABA
      release and reduced that of DA in response to 50 microM NMDA whereas treatment
      with an NO-donor (SNAP; 10 microM) significantly reduced evoked ACh, ASP and GLU
      release. The NO synthase inhibitor L-NARG potentiated kainate-evoked ACh release
      and reduced that of DA, although less potently than NMDA, but it had no effect on
      KCl-evoked transmitter release. Overall, these results show that both NMDA and
      kainate increase striatal NO release at similar dose-thresholds as for classical
      transmitter release suggesting that NO is dynamically released under
      physiological and not just pathological conditions. Reductions of striatal NO
      levels also potentiates calcium-dependent transmitter release in response to NMDA
      and, to a lesser extent, kainate, whereas increasing them reduces it. This is
      consistent with a role for NO as a neuroprotective agent in this region acting to
      desensitize NMDA receptors.

PMID- 8996813
TI  - The nitric oxide/cyclic GMP messenger system in olfactory pathways of the locust
      brain.
AB  - Nitric oxide is generated by a Ca2+/calmodulin-stimulated nitric oxide synthase
      and activates soluble guanylyl cyclase. Using NADPH diaphorase (NADPHd) staining
      as a marker for the enzyme nitric oxide synthase and an antiserum against cGMP,
      we investigated the cellular organization of nitric oxide donor and target cells
      in olfactory pathways of the brain of the locust (Schistocerca gregaria). A small
      subset of neuronal and glial cells expressed cGMP immunoreactivity after
      incubation of tissue in a nitric oxide donor. Nitric oxide-induced increases in
      cGMP immunoreactivity were quantified in a tissue preparation of the antennal
      lobe and in primary mushroom body cell cultures. The mushroom body neuropil is a
      potential target of a transcellular nitric oxide/cGMP messenger system since it
      is innervated by extrinsic NADPHd-positive neurons. The mushroom body-intrinsic
      Kenyon cells do not stain for NADPHd but can be induced to express cGMP
      immunoreactivity. The colocalization of NADPHd and cGMP immunoreactivity in a
      cluster of interneurons of the antennal lobe, the principal olfactory neuropil of
      the insect brain, suggests a role of the nitric oxide/cGMP system in olfactory
      sensory processing. Colocalization of NADPHd staining and cGMP immunoreactivity
      was also found in certain glial cells. The cellular organization of the nitric
      oxide/cGMP system in neurons and glia raises the possibility that nitric oxide
      acts not only as an intercellular but also as an intracellular messenger molecule
      in the insect brain.

PMID- 8996814
TI  - Altered gene expression of the N-methyl-D-aspartate receptor channel subunits in
      Purkinje cells of the staggerer mutant mouse.
AB  - The gene expression of five NMDA receptor channel subunits, the epsilon(1),
      epsilon(2), epsilon(3), epsilon(4) and zeta(1) subunits, was examined in
      cerebellar Purkinje cells of the staggerer mouse at postnatal day 21. In the
      midline region of the staggerer cerebellum, signals for the epsilon(1),
      epsilon(4) and zeta(1) subunit mRNAs were distributed in Purkinje cells, which
      have a large cell body aligned in a monolayer between the granular and molecular
      layers. In addition to the midline region, labelled neurons in the intermediate
      cerebellar region were, though at lower levels, aligned almost in a monolayer
      between the granular and molecular layers. In the hemisphere, most labelled
      neurons occurred in various locations in the granular layer and the cerebellar
      medulla. These regions, populated with Purkinje cells expressing the epsilon(1),
      epsilon(4) and zeta(1) subunit mRNAs, were separated from each other by narrow
      gap regions that contained neurons without any detectable NMDA receptor channel
      subunit mRNAs. These results suggest that there is discrete mediolateral
      heterogeneity in staggerer Purkinje cell populations, in terms of expression
      properties of the NMDA receptor channel subunits. When compared with wild-type
      Purkinje cells that express the zeta(1) subunit alone, additional expression of
      the epsilon subunits presumably explains the persistence of NMDA responses in
      adult staggerer Purkinje cells (Dupont et al., Neuroscience, 12, 613-619, 1984).

PMID- 8996815
TI  - Injury-induced synthesis and release of apolipoprotein E and clusterin from rat
      neural cells.
AB  - Apolipoproteins in the brain have assumed major clinical importance since it was
      shown that one of the allelic forms of apolipoprotein E, apoE-4, is a risk factor
      for Alzheimer's disease. Using tissue culture of embryonic rat spinal cord, we
      examined the effect of neuronal injury on the up-regulation of two
      apolipoproteins, apolipoprotein E and clusterin (apoJ). In order to study the
      influence of neuronal cells, we exploited the specific neurotoxic effect of
      elevated glutamate on these cells. Overstimulation by excess glutamate induced
      neuronal degeneration as assessed by morphological and biochemical criteria,
      notably the activity of choline acetyltransferase, which serves as a marker for
      cholinergic neurons. High concentrations of glutamate increased mRNA synthesis
      and the production and secretion of both apolipoprotein E and clusterin protein.
      Both neuronal cell death and release of the peptides were calcium-dependent and
      could be blocked by the NMDA receptor antagonist MK-801. Immunohistochemical data
      revealed the presence of clusterin in both neuronal and non-neuronal cells
      whereas apolipoprotein E was mainly expressed in non-neuronal cells. The results
      are suggestive of concerted up-regulation of apolipoprotein E and clusterin when
      neural cells are subjected to injury.

PMID- 8996816
TI  - Sodium current amplitude increases dramatically in human retinal glial cells
      during diseases of the eye.
AB  - Muller cells, the main macroglial cells of the retina, express several types of
      voltage and ligand-activated ion channels, including Na+ channels. Using the
      whole-cell voltage-clamp technique, we studied the expression of Na+ currents in
      acutely isolated, non-cultivated human Muller cells from retinas of healthy organ
      donors and patients suffering from different eye diseases. In both types of
      retinas transient Na+ currents could be recorded from Muller cells. The
      tetrodotoxin-resistant Na+ currents, which were not completely blocked even at a
      concentration of 10 microM tetrodotoxin, had a mean current density of 3.0 +/-
      3.0 pA/pF (mean +/- SD, n = 10) in Muller cells from donor retinas and of 12.2 +/
      9.6 pA/pF (n = 74) in Muller cells from patient retinas. Only 33.3% of healthy
      but 88.4% of pathological Muller cells depicted such currents. The GNa+/GK+ ratio
      was very high in several Muller cells from patient retinas, such that action
      potential-like activity could be generated after prehyperpolarizing current
      injection in some of these cells. Apparently, the Na+ channels, due to their
      negative steady-state inactivation curve (Vh = -84.5 mV), do not influence the
      lowered membrane potential of the pathological cells, since they are inactivated
      at these voltages. Currently, we do not have an explanation for the increase in
      amplitude and frequency of Na+ currents in human Muller cells under pathological
      conditions. However, the up-regulation of Na+ channels may mirror a basic glial
      response to pathological conditions, since it has also been found previously in
      human hippocampal astrocytes from epileptic foci and in rat cortex stab wounds
      lined by an astrocytic scar.

PMID- 8996817
TI  - Protein kinases in the rat nucleus accumbens are involved in the aversive
      component of opiate withdrawal.
AB  - The specific participation of protein kinases in the expression of the somatic
      signs of morphine withdrawal has been previously demonstrated, suggesting that
      changes in intracellular signalling systems are involved in opioid addiction. In
      the present study, the involvement of protein kinases in the aversive/dysphoric
      effects of morphine abstinence has been investigated in the nucleus accumbens,
      because of the critical role played by the mesolimbic system in the rewarding
      effects of opioids. Rats were chronically treated with morphine, twice a day for
      5 days, with doses progressively increased from 5 to 30 mg/kg (i.p.). In
      addition, microinjections into the nucleus accumbens of the serine-threonine
      kinase inhibitors H7 or H8 (1 or 10 nmol per side) or saline once daily were also
      given, both in control and in morphine-treated animals. After these chronic
      treatments, withdrawal syndrome was induced by naloxone administration (0.1
      mg/kg, s.c.), and the motivational component of morphine abstinence was studied
      using the place aversion paradigm. When administered at the highest dose (10
      nmol), H7 and H8 strongly reduced the place aversion induced by naloxone in
      morphine dependent animals. Protein kinase inhibitors did not induce significant
      behavioural responses in non-dependent animals. Chronic morphine treatment
      induced a selective up-regulation of adenylate cyclase activity in the amygdala,
      without affecting other brain regions. The morphine-increased adenylate cyclase
      activity in amygdala was reversed by the chronic intra-accumbens microinjections
      of H7 and H8. These results suggest that serine-threonine kinases in the nucleus
      accumbens play an important role in the emotional/dysphoric properties which
      characterize opiate withdrawal.

PMID- 8996818
TI  - Rat brain: distribution of immunoreactivity of PE-11, a peptide derived from
      chromogranin B.
AB  - An antiserum was raised against the peptide PE-11 whose sequence is present in
      the chromogranin B molecule. The antiserum reacts only with the free C-terminal
      end of this peptide. PE-11 immunoreactivity in brain was characterized by
      molecular size exclusion high performance liquid chromatography. Only the free
      peptide and a N-terminally elongated peptide were detected, indicating that
      proteolytic processing of chromagranin B in brain is quite extensive. In
      immunohistochemistry PE-11 immunoreactivity was found in varicosities, fibres and
      perikarya throughout the brain. Strong staining was detected in the shell sector
      of the nucleus accumbens, in the lateral septum, in subregions of the extended
      amygdala, in some areas of the hippocampus and of the hypothalamus, in the locus
      coeruleus, in the Purkinje cells of the cerebellum and in the dorsal horn of the
      spinal cord. Our results, which demonstrate significant processing of
      chromogranin B in brain and its widespread distribution, can be taken as an
      indication that chromogranin B represents a precursor of peptides with functional
      relevance for this organ.

PMID- 8996819
TI  - Postsynaptic currents and short-term synaptic plasticity in Purkinje cells
      grafted onto an uninjured adult cerebellar cortex.
AB  - It has been shown recently that embryonic Purkinje cells grafted
      extraparenchymally into an intact cerebellum, in the absence of any sign of
      damage, are able to migrate into the host molecular layer where they receive a
      climbing fibre innervation. Using the same technique, we investigated the
      development of the electrophysiological properties of the synapses between the
      grafted cells and their main afferents. Purkinje cells either in the graft or
      having migrated into the molecular layer of the host were recorded using the
      whole-cell patch-clamp method in acutely prepared slices 17-112 days after
      grafting. Spontaneous postsynaptic currents with a single-exponential decay and
      mediated by GABAA receptors were very similar to those described in normal
      Purkinje cells. Excitatory postsynaptic currents (EPSCs) evoked by climbing fibre
      and by parallel fibre stimulation were blocked by an alpha-amino-3-hydroxy-5
      methyl-4-isoxazole-propionic acid (AMPA)/kainate antagonist, and displayed the
      linear current-voltage relation typical of postnatal Purkinje cells. The
      attainment of normal functional properties by the adult axons at the newly formed
      synaptic sites was shown by the expression of short-term facilitation of parallel
      fibre EPSCs and of short-term depression of climbing fibre EPSCs. The grafted
      Purkinje cells showed climbing fibre polyinnervation 17-20 days after grafting
      which evolved to monoinnervation at 23-45 days, confirming the completion of the
      developmental programme up to maturation. Our experiments support the view that
      the adult intact brain is able to accept and integrate an additional number of
      neurons which show fully mature electrophysiological properties which are
      electrophysiologically indistinguishable from those of the host neurons.

PMID- 8996820
TI  - The cerebral cortex and parafascicular thalamic nucleus facilitate in vivo
      acetylcholine release in the rat striatum through distinct glutamate receptor
      subtypes.
AB  - Electrical stimulation (ten pulses of 0.5 ms, 10 V applied over 10 s at 10 Hz,
      140 microA) delivered bilaterally to the prefrontal cortex or the parafascicular
      thalamic nucleus of freely moving rats facilitated acetylcholine release in
      dorsal striata, assessed by trans-striatal microdialysis. The facilitatory
      effects were blocked by coperfusion with 5 microM tetrodotoxin, suggesting that
      the release was of neuronal origin. The response of the striatal cholinergic
      neurons to prefrontal cortical stimulation was short-lived and required a longer
      period of stimulation (20 min) that the response to thalamic stimulation (4 min)
      to reach maximal effect. The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA)/kainate glutamatergic receptor antagonist 6,7-dinitroquinoxaline-2,3
      dione [DNQX; 12 nmol per side, intracerebroventricularly (i.c.v.)] and the AMPA
      antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX; 12 nmol per
      side, i.c.v. or 12.8 microM infused into the striatum), but not the NMDA-type
      receptor antagonist MK-801 (0.2 mg/kg, i.p.), abolished the facilitatory effect
      on striatal acetylcholine release evoked by stimulation of the prefrontal cortex.
      By contrast, DNQX or NBQX did not prevent the increase in striatal acetylcholine
      release evoked by parafascicular nucleus stimulation, but MK-801, in accordance
      with previous results, did so. MK-801 by itself lowered striatal acetylcholine
      output while DNQX and NBQX did not. The results provide in vivo evidence that the
      cerebral cortex facilitates cholinergic activity in the dorsal striatum
      apparently through the non-tonic activation of AMPA-type glutamatergic receptors
      while the parafascicular nucleus does this through tonic activation of NMDA
      receptors. Both glutamate receptor types are probably located in the striatum.
      The overall results suggest that the two pathways operate independently to
      regulate striatal cholinergic activity through distinct mechanisms.

PMID- 8996821
TI  - Status epilepticus causes selective regional damage and loss of GABAergic neurons
      in the rat amygdaloid complex.
AB  - In human epilepsy, the amygdala is often a primary focus for seizures. To analyse
      the status epilepticus-induced alterations in the amygdaloid circuitries which
      may later underlie epileptogenesis, we studied the amygdaloid damage in kainic
      acid and perforant pathway stimulation models of status epilepticus in the rat.
      We also studied the damage to inhibitory GABAergic neurons. In both models, the
      medial division of the lateral nucleus, the parvicellular division of the basal
      nucleus and portions of the anterior cortical and medical nuclei were damaged. In
      the kainate model, where the seizure activity was more severe, the accessory
      basal nucleus, amygdalohippocampal area, posterior cortical nucleus and
      periamygdaloid cortex were also damaged. Two weeks after kainate-induced
      seizures, 56% of the GABA-immunoreactive neurons remained in the lateral nucleus
      (P < 0.05) and 25% in the basal nucleus (P < 0.01). Further analysis showed that
      one subpopulation of damaged GABAergic neurons was immunoreactive for
      somatostatin (48% remaining in the lateral nucleus, P < 0.01; 33% in the basal
      nucleus, P < 0.01). In the perforant pathway stimulation model, the damage to
      somatostatin neurons was milder. According to our data, the initial insult, such
      as status epilepticus, selectively damages amygdaloid nuclei. The loss of
      inhibition may underlie the spontaneous generation of seizures and
      epileptogenesis. On the other hand, many amygdaloid output nuclei (magnocellular
      and intermediate division of the basal nucleus, the central nucleus) remained
      relatively undamaged, providing pathways for seizures spread and generation of
      seizure-related behavioural manifestations such as motor convulsions and fear
      response.

PMID- 8996822
TI  - Micro-organization of olivocerebellar and corticonuclear connections of the
      paravermal cerebellum in the cat.
AB  - The olivocerebellar and corticonuclear connections of the forelimb area of the
      paravermal medial C3 zone were studied in the cat using a combined
      electrophysiological and fluorescent tracer technique. During an initial
      operation under barbiturate anaesthesia, lobules IV/V of the cerebellar anterior
      lobe were exposed and small injections of dextran amines tagged with rhodamine or
      fluorescein were made into areas selected from four different
      electrophysiologically defined parts of the zone. The inferior olive and the deep
      cerebellar nuclei were then scrutinized for retrogradely labelled cells and
      anterogradely labelled axon terminals respectively. The findings demonstrate a
      detailed topographical organization within the olivocerebellar projection to the
      medial C3 zone and provide some evidence for a topographical organization of its
      projection to nucleus interpositus anterior. Both projections are described at a
      level of resolution not previously attained in neuroanatomical studies and the
      results strongly support the notion of a micro-compartmentalization of cerebellar
      olivo-corticonuclear circuits.

PMID- 8996824
TI  - Developmental study of N-methyl-D-aspartate-induced firing activity and whole
      cell currents in nucleus tractus solitarii neurons.
AB  - Whole-cell recordings of rat nucleus tractus solitarii (NTS) neurons were
      performed on a slice preparation. We investigated possible postnatal changes in
      firing activities and currents induced by N-methyl-D-aspartate (NMDA)
      application. A total of 42 neurons were selected and fell into the following age
      groups: 0-5 days (n = 15), 10-15 days (n = 9) and 30-60 days (adult, n = 18).
      During this period, input resistance and spike duration decreased by
      approximately 40%. At all ages, bath application of NMDA elicited a bursting
      firing activity when the membrane potential was held between -60 and -75 mV.
      However, in the youngest cells the rhythmic bursting activity was irregular and
      was characterized by a progressive firing inactivation during a burst. In a
      tetrodotoxin-containing saline, NMDA-induced oscillations of membrane potential
      were retained in all age groups. The membrane current-voltage relationship of the
      NMDA-induced inward current (INMDA) was characterized by a region of negative
      slope conductance which was similar in all age groups. Thus the voltage-dependent
      block of INMDA is present in NTS neurons from birth, allowing NTS neurons to
      display membrane potential oscillations. However, postnatal maturation of
      repolarizing conductances, as suggested by changes in spike characteristics,
      could render the oscillatory activity more stable than at birth.

PMID- 8996823
TI  - Dystroglycan in the cerebellum is a laminin alpha 2-chain binding protein at the
      glial-vascular interface and is expressed in Purkinje cells.
AB  - Dystroglycan is a core component of the dystrophin receptor complex in skeletal
      muscle which links the extracellular matrix to the muscle cytoskeleton.
      Dystrophin, dystrophin-related protein (DRP, utrophin) and dystroglycan are
      present not only in muscles but also in the brain. Dystrophin is expressed in
      certain neuronal populations while DRP is associated with perivascular
      astrocytes. To gain insights into the function and molecular interactions of
      dystroglycan in the brain, we examined the localization of alpha- and beta
      dystroglycan at the cellular and subcellular levels in the rat cerebellum. In
      blood vessels, we find alpha-dystroglycan associated with the laminin alpha 2
      chain-rich parenchymal vascular basement membrane and beta-dystroglycan
      associated with the endfeet of perivascular astrocytes. We also show that alpha
      dystroglycan purified from the brain binds alpha 2-chain-containing laminin-2.
      These observations suggest a dystroglycan-mediated linkage between DRP in
      perivascular astrocytic endfeet and laminin-2 in the parenchymal basement
      membrane similar to that described in skeletal muscle. This linkage of the
      astrocytic endfeet to the vascular basement membrane is likely to be important
      for blood vessel formation and stabilization and for maintaining the integrity of
      the blood-brain barrier. In addition to blood vessel labelling, we show that
      alpha-dystroglycan in the rat cerebellum is associated with the surface of
      Purkinje cell bodies, dendrites and dendritic spines. Dystrophin has previously
      been localized to the inner surface of the plasma membrane of Purkinje cells and
      is enriched at postsynaptic sites. Thus, the present results also support the
      hypothesis that dystrophin interacts with dystroglycan in cerebellar Purkinje
      neurons.

PMID- 8996825
TI  - Localization of the serotonin transporter in rat spinal cord.
AB  - The spinal cord is richly innervated by serotoninergic fibres originating from
      the raphe nuclei. The localization of the terminating component of serotoninergic
      neurotransmission, the serotonin transporter SERT1, was found in both the dorsal
      and ventral horns, especially at the level of the cervical and lumbar segments.
      Within the thoracic region, we observed a heavily labelled bundle in the
      intermediolateral nucleus of lamina VII. A low density of stained fibres was
      encountered in the sacral spinal cord. In contrast to homogeneous staining of
      motor nuclei, a differential labelling of laminae was seen in the dorsal horn,
      with laminae I, III and IV exhibiting a higher density of immunopositive
      terminals than the medial part of lamina II. High magnification revealed a
      preferential accumulation of serotonin transporter staining within nerve endings
      and varicosities of thin fibres. Double immunofluorescence staining demonstrated
      a co-localization of serotonin and its uptake system within these varicosities.
      These results show that the serotonin transporter is highly expressed in the rat
      spinal cord and that its distribution parallels the serotoninergic innervation.
      They also reinforce the view that varicosities are important neuronal structures,
      which modulate the function of dorsal and ventral horn neurons by releasing
      serotonin.

PMID- 8996826
TI  - Alzheimer's disease research: a game of connect the dots.
AB  - Although a vast number of experimental investigations have focused on various
      aspects of Alzheimer's disease (AD), the pathogenic mechanism of the disease has
      not been established. AD research is a dynamically changing field that has
      entertained a variety of hypotheses. Since most of the data pertaining to AD
      pathogenesis is obtained in postmortem tissue or in vitro experiments,
      researchers must play a game of 'connect the dots' to try to correlate the
      diverse aspects of the disease and generate hypotheses regarding the sequence of
      pathological events. This article reviews the current state of AD research, and
      presents three hypothetical models for disease progression.

PMID- 8996827
TI  - Theoretical considerations on the nature of the pineal 'ageing clock'.
AB  - The models developed in our laboratory demonstrate that ageing initiates and
      progresses in the pineal gland. However, the ageing postponing effects of pineal
      grafting into older recipients cannot be explained by a simple maintenance and/or
      normalization of the night melatonin synthesis and release. We propose here that
      the pineal gland monitors and regulates, via its control of neuroendocrine
      function, the maintenance of 'self-identity' and the capacity of the immune
      system to recognize and react against any noxious, endogenous or exogenous agent.
      Senescence is characterized by the extinction of this central pineal function.
      The progressive decline of the self-recognition capacity distinguishes the
      typical diseases of ageing expressed as emergence of peripheral desynchronization
      and autoimmune, anaplastic, neoplastic and degenerative processes. Our approaches
      aim at a prevention and/or restoration of central pineal functions.

PMID- 8996828
TI  - Cerebromicrovascular pathology in Alzheimer's disease compared to normal aging.
AB  - A growing amount of data using light and electron microscopy,
      immunocytochemistry, uptake of brain markers and metabolic studies suggest that
      the pathogenesis of Alzheimer's disease may be due to impaired vascular delivery
      of nutrients to the brain. The bulk of this evidence indicates that cerebral
      capillary transport of glucose, oxygen and other vital nutrients is dysfunctional
      in Alzheimer brains due to abnormal hemodynamic flow patterns caused by
      structural deformities of the capillaries. Clinical disorders which can worsen
      cerebral blood flow, such as head injury, coronary artery disease,
      cerebrovascular ischemia or the presence of apolipoprotein E4 allele will
      increase the risk of Alzheimer's dementia. By contrast, activities that increase
      cerebral blood flow during aging such as complex thinking patterns or the use of
      drugs to reduce vascular resistance, such as aspirin or NSAIDs, will reduce the
      risk or improve the status of Alzheimer's disease. The production of neuritic
      plaques and neurofibrillary tangles may develop from the hypometabolic
      abnormalities caused by the impaired cerebromicrovasculature in Alzheimer brains.
      Such metabolic and cerebral blood flow changes are considerably less significant
      in age-matched control subjects. The major physiological, pathological and
      cognitive changes reported for Alzheimer's disease appear to have a common
      denominator which is reflected by the physically distorted cerebromicrovessels
      and their inability to optimally deliver nutrients to the brain, a condition
      which ultimately disturbs neurono-glial homeostasis.

PMID- 8996829
TI  - Brain and erythrocyte anion transporter protein, band 3, as a marker for
      Alzheimer's disease: structural changes detected by electron microscopy,
      phosphorylation, and antibodies.
AB  - Band 3, a ubiquitous membrane transport, regulatory, and structural protein, is
      represented in brain by at least 4 isoforms. Bands 3 in brain performs the same
      functions as it does in erythrocytes (RBC). It is susceptible to oxidative
      damage, which, ultimately, terminates its life and that of the cell. We examined
      the changes band 3 undergoes in Alzheimer's disease (AD) because our previous
      studies suggest that band 3 is a pivotal protein in neurological disease. Because
      we hypothesize that AD is a total body disease, we examined peripheral blood
      cells as well as brain tissue to determine whether the same changes occur in
      both. Our results indicate that posttranslational changes occur in RBC band 3
      that parallel changes in brain band 3. These include decreased 32P-phosphate
      labeling in vitro of band 3 polypeptides in brain and RBC, increased degradation
      of band 3, alteration in band 3 recognized by polyclonal and monoclonal
      antibodies, and decreased anion and glucose transport by blood cells. Serum
      autoantibodies to band 3 peptides 588-602 and 822-839 were increased in AD
      patients compared to controls. These band 3 residues lie in anion
      transport/binding regions. This is consistent with alteration of this region in
      AD since it is recognized as antigenically different by the patients' immune
      system. Our data support an immunological component to AD. The finding that
      changes in RBC in AD reflect those in brain and can be recognized by antibodies
      should facilitate development of blood tests for diagnosis and monitoring, and
      early therapy. It is anticipated that identification of molecular sites of
      posttranslational modification of band 3 will enable us to design specific
      preventive and treatment strategies, and target drugs to crucial molecular sites.

PMID- 8996831
TI  - Neuroautoimmunity: pathogenic implications for Alzheimer's disease.
AB  - Immune factors such as cellular immunity, autoimmunity, and inflammation may play
      a pathogenic role in Alzheimer's disease (AD), a neurodegenerative disorder.
      Based on immunologic dysregulation in many patients, a neuroautoimmunity (NAI)
      model is proposed which suggested a CD8+ cell-mediated mechanism (activated
      cytotoxic T lymphocytes); CD4+ suppressor/inducer (2H4+) cells may also be
      involved. Antibrain antibodies may contribute through a cell-specific autoimmune
      assault leading to neurodegeneration of the AD type. Thus, a cell-mediated
      autoimmune response against brain antigens may explain the immune subset of AD.

PMID- 8996830
TI  - Involvement of neuronal anion exchange proteins in cell death in Alzheimer's
      disease.
AB  - Anion exchange (AE) proteins are present in human neurons in the brain.
      Immunohistochemical data indicate that their apparent expression level increases
      with age, and especially with degeneration in Alzheimer's disease-affected brain
      areas. The increase in immunoreactivity is probably caused by changes in AE
      structure that lead to an increased accessibility of hitherto hidden epitopes.
      These epitopes correspond to regions in the membrane domain that are involved in
      generation of senescent cell-specific antigen from AE1 in aging erythrocytes.
      Elucidation of the molecular nature of these changes and the underlying
      mechanisms, will lead to insight in the processes that govern aging- and
      degeneration-associated perturbation of membrane integrity. AE-mediated
      chloride/bicarbonate exchange is a major component in the regulation of
      intracellular pH. The functional consequences of changes in AE structure may
      range from acidosis, disturbance of cytoskeleton integrity, and untimely or
      impaired recognition of cells by components of the immune system, such as
      microglia. A molecular and physiological description of these changes will
      establish AE proteins as valuable tools in elucidating the processes of normal
      aging, and the disturbances in aging-related diseases such as Alzheimer's
      disease.

PMID- 8996832
TI  - Microglial in neurodegenerative disorders: emphasis on Alzheimer's disease.
AB  - Hallmark lesions of Alzheimer's disease (AD) are filled with reactive
      immunocompetent microglia, suggesting that immunological aberrations may
      participate in the pathophysiology of this disorder. If immune-mediated processes
      are closely linked to neuronal breakdown it would be of importance to have a
      reliable means to detect these processes. Cerebrospinal fluid microglial
      antibodies found mainly in AD patients are discussed as such potential sources.
      These antibodies recognize microglia in the developing rat brain, in neuronal
      cultures and on AD cortical biopsies. Treatment aimed at downregulating
      microglial is discussed and may have therapeutic significance for AD patients.
      Largely this review presents current opinions which support the concept that
      inflammation and similar immune mechanisms need to be considered as participating
      in AD pathogenesis.

PMID- 8996833
TI  - Glial cells in Alzheimer's disease: preferential effect of APOE risk on scattered
      microglia.
AB  - Reactive glial cells are consistently found in the brain tissue of Alzheimer's
      disease (AD) patients. Both clustered and scattered glial cells occur in AD
      brain. A number of clustered microglial cells, but not astrocytes, had a positive
      correlation with neurite plaque numbers, suggesting that clustered micro-glial
      cells are uniquely associated with plaques whereas clustered astrocytes may have
      functions outside the plaques as well. APOE epsilon 4, the major genetic risk
      factor for AD, had a dose-dependent effect to increase the numbers of scattered
      microglial cells whereas the APOE risk showed no correlation with any of the
      clustered glial cells or scattered astrocytes. These findings raise the
      possibility that the increased levels of scattered, but not clustered, microglial
      cells are the immediate response to APOE risk and might be primarily involved in
      AD pathogenesis.

PMID- 8996834
TI  - Expression of the APP gene family in brain cells, brain development and aging.
AB  - The Alzheimer's beta A4-amyloid protein precursor (APP) and the APP-like proteins
      (APLPs) are transmembrane glycoproteins with a similar modular domain structure.
      Alternatively spliced exons found in both genes comprise a Kunitz protease
      inhibitor domain encoding exon, and another exon within the divergent regions
      adjacent to the transmembrane domain, i.e. exon 15 of the APP gene and an exon
      encoding 12 residues in APLP2. Omission of the latter exons in L-APP and L-APLP2
      isoforms, respectively, generates a functional recognition sequence for
      xylosyltransferase-mediated addition of glycosaminoglycans and proteoglycan
      formation. In this paper, we summarize our analyses of the regulated expression
      of these alternatively spliced exons in APP and APLP2 in primary cultured rat
      brain cells, rat brain development and aging. In conjunction with additional data
      for the human brain, these data provide important clues for understanding the
      functional significance of alternative splicing and glycosylation in APP biology.
      On the basis of recent results showing a higher amyloidogenicity of exon 15
      encoding APP than L-APP isoforms, we further discuss the potential significance
      of the low levels of L-APP in neurons for the susceptibility of the brain towards
      Alzheimer's disease.

PMID- 8996835
TI  - Alzheimer's, ageing and amyloid: an absurd allegory?
AB  - Recent research into the pathogenesis of Alzheimer's disease (AD) has focused
      upon the proposed neurotoxic role played by the beta-amyloid peptide. Other
      important neurochemical disturbances, such as the dramatic breakdown of
      intracellular signalling, should however not be overlooked. In the present
      article, the authors attempt to investigate the relationship between signalling
      disturbances and beta-amyloid and ask the question 'which came first?' The
      available evidence is discussed, and it is concluded that the need for a wide,
      rather than restricted, focus on biochemical events associated with AD is
      required if progress is to be made in the understanding and eventual treatment of
      this disease.

PMID- 8996836
TI  - Inflammation and Alzheimer's disease: mechanisms and therapeutic strategies.
AB  - Inflammatory mechanisms in the brain may contribute to the neurodegenerative
      process in Alzheimer's disease. The cerebral acute-phase response mediated by
      inflammatory cytokines, the complement cascade, and the accumulation of activated
      microglial cells are appropriate targets for anti-inflammatory intervention.
      Pilot studies showed that tolerable doses of prednisone suppress the peripheral
      acute-phase response in Alzheimer's disease, and a multicenter therapeutic trial
      of prednisone is in progress. Two other anti-inflammatory drugs,
      hydroxychloroquine and colchicine, are also under investigation.

PMID- 8996837
TI  - [Analysis of hepatitis C virus (HCV) genotypes in hepatocellular carcinoma].
AB  - Chronic hepatitis C virus (HCV) infection has been clearly established as a major
      risk factor in the development of hepatocellular carcinoma. In the present study
      we have attempted to identify the HCV genotypes associated with hepatocellular
      carcinoma in patients from the USA and Japan. RNAs from tumorous and non-tumorous
      tissues from 11 HCV seropositive Japanese patients, and plasma from 4 American
      patients were analysed by reverse transcription-polymerase chain reaction (RT
      PCR) methods employing primers specific for the 5'UTR, the NS5 and E2/NS1
      regions. Amplified products were cloned and compared by nucleotide sequencing and
      phylogenetic analysis. The 5'UTR region could be successfully amplified and
      sequenced from all samples, and phylogenetic analysis of the nucleotide sequences
      demonstrated with the exception of two of Japanese viruses were closely related
      to HCV type 1. Type 2 was detected in these two cases. In addition, two of the
      Japanese patients who were found to have cholangiocarcinoma were also found to be
      infected with type 1. HCV amplification of the NS5 was successful in 7 of the
      Japanese and 1 USA sample and clearly demonstrated that genotype 1b was
      predominant. Amplification of the E2/NS1 regions proved to be extremely difficult
      and was unsuccessful in all HCC patients despite the fact that these regions
      could be consistently amplified in samples from patients with both acute and
      chronic HCV infection. These findings might suggest that with long term
      persistent HCV infection, there may be marked heterogeneity in both the
      structural and non-structural regions of the virus, and/or possibly that the
      viral genomes may be defective.

PMID- 8996838
TI  - [Chemosensitivity test on hepatocellular carcinoma (HCC) and drug resistance].
AB  - 10 HCC cell lines and 122 surgically resected HCC were studied on
      chemosensitivity to 6 anticancer agents. Succinic dehydrogenase inhibition test
      was used for evaluating chemosensitivity of HCC. The HCC cell lines were positive
      in sensitivity to the most anticancer agents except 5-FU. Sensitivity of resected
      HCC specimens was positive in 17/42 (40.5%) to exposed to VP-16, in 21/57 (36.8%)
      to IFM, but also it was positive in 40/46 (87.0%) of the non-cancer tissue of the
      same liver exposed to VP-16 and in 33/60 (55.0%) to IFM. So VP-16 and IFM were
      probably considered to injure the residual liver after hepatectomy. In
      immunostainings of P-gp, GST-pi, MT, and P-450 of HCC cell lines, the expression
      of P-gp correlated with MDR1 mRNA and chemosensitivity test to ADM. Correlation
      between the expression of GST-pi and chemosensitivity test to ADM and CDDP were
      considered to be probably recognized. However, in surgically resected HCC,
      correlation among those factors was not observed. IN CONCLUSION: P-gp, MDR1 gene
      and GST-pi have probably a role in drug resistance in HCC. Selection of
      anticancer agents after chemosensitivity tests on both HCC and normal tissue of
      liver should be performed. We need more investigation for how the results of
      chemosensitivity test correlate with clinical effectiveness.

PMID- 8996839
TI  - [The limits of resection in hepatopancreatectomies in rats].
AB  - Hepatopancreatectomy (HPx), one of the most stressful surgeries, is occasionally
      the only curative resection for widely spreading biliary cancer. Little is known
      about the pathophysiology after HPx. This study was undertaken to investigate the
      limits of resection and to compare HPxs with respect to morphological and
      biochemical findings in order to establish reasonable models of HPxs in rats.
      Male Wistar rats underwent 6 kinds of HPxs. The HPxs performed were a combination
      of one of 3 degrees of hepatectomy (70%, 80%, or 90%) and one of 2 degrees of
      pancreatectomies (60% or 90%). Hepatectomy (Hx) alone and pancreatectomy (Px)
      alone were used as the controls. The animals were observed with checks on
      mortality, body weight, and blood sugar level. On day 28, they were sacrificed in
      order to obtain the liver and pancreas tissue and systemic blood. According to
      direct survival rate on day 28, the six kinds of HPxs were classified into four
      as follows: safe HPx (70% Hx + 60% Px, survival rate 100%; and 70% Hx + 90% Px,
      survival rate 88.2%); critical HPx (80% Hx + 60% Px, survival rate 52.9%); poor
      HPx (80% Hx + 90% Px, survival rate 31.3%; and 90% Hx + 60% Px, survival rate
      25.0%); and fatal HPx (90% Hx + 90% Px, survival rate 0%). In the rats which
      underwent HPxs, 46 out of 49 deaths (95.8%) occurred in the first three
      postoperative days. In survivors receiving the critical and poor HPxs,
      morphological and biochemical values were within permissible ranges, comparable
      with those of the rats receiving 70% Hx or 60% Px. In conclusion, 70% Hx + 90% Px
      was considered to be a safe limit for HPx, and 80% HX + 60% Px was considered to
      be a borderlining limit for HPx; sufficient recovery after operation would be
      expected since some rats survived even after critical and poor HPxs. Vitally
      physiological changes would be expected to occur in the early postoperative
      period.

PMID- 8996840
TI  - [Establishment of an estrogen receptor positive 3'-methyl-4
      dimethylaminoazobenzene induced hepatoma cell line of rat and investigation of
      hormonal therapy].
AB  - An estrogen receptor (ER) positive cell line was newly established from a Wistar
      King Aptekman (WKA) rat, 3'-methyl-4-dimethylaminoazobenzene (DAB) induced
      hepatoma cell lines. The impact of hormonal therapy on cell growth was
      investigated. This cell line produced alpha-fetoprotein (AFP), carcinoembryonic
      antigen (CEA) and ferritin in the conditioned medium. Progesterone receptors
      (PgR) were positive but androgen receptors (AR) were not detected. This cell
      line's doubling time was about 10.5 hours in a routine medium and 12.2 hours in
      the endogenous estrogen removed medium (exponential phase). The morphological
      features of the cell were of a hepatocellular type as observed by light
      microscopy. The modal chromosome number was 56 and the DNA ploidy pattern was
      aneuploid as observed by flow cytometry. The addition of 17 beta-estradiol (E2)
      did not increase cell growth but tamoxifen (TAM) in vitro inhibited cell growth
      in the lag phase. Surgical castration or oral administration of E2 or TAM in vivo
      inhibited tumor growth in the early phase. There were no additional effects
      between surgical castration and the administration of E2. Surgical castration
      plus the administration of TAM were not effective when combined. The
      administration of TAM caused the physiological effect of castration eg.,
      diminished blood testosterone level same as E2 administration. TAM also decreased
      the maximal binding capacity (Bmax) of ER. A morphological change to the
      cholangiocell carcinoma type was noticed. These results that this cell line was
      ER dependent in the early phase of tumor growth.

PMID- 8996841
TI  - [Hypoglycemic effect and enhanced gastrointestinal absorption of insulin using
      new cinnamoyl-phenylalanine derivatives].
AB  - To find a new adjuvant for oral administration of Insulin (IN), we examined the
      gastrointestinal absorption and hypoglycemic effect of new IN-Cinnamoyl (Cin)
      Phenylalanine (Phe) derivative preparations administered orally or
      intraduodenally to fasted normal and Streptozotocin (STZ)-diabetic animals.
      Selected IN.N-alpha-Chlorocinnamoyl-D-Phenylalanine (A-3989) and IN.N-alpha
      Chloro-4-methyl-cinnamoyl-D-phenylalanine (A-4266) preparations among 80 of
      IN.Cin-Phe derivative preparations administered orally or intraduodenally
      promoted absorption of IN from the gastrointestinal tract resulting in
      significantly elevated serum IN levels and reduced serum glucose levels in fasted
      normal and Streptozotocin (STZ)-diabetic animals. Especially, IN.A
      3989(25U.150mg/kg) and IN.A-4266(12.5U.150mg/kg) preparation administered
      intraduodenally represented marked enhanced IN absorption in normal mice and area
      under the serum IN concentration vs. time curve (AUC) showed 97.5 and 49.3
      (mU.min/ml), respectively. Furthermore, A-3989 and A-4266 were found to exert
      inhibitory effect on IN degradation by partially purified mouse intestinal
      enzyme. IN.A-4266 (25U.200mg/kg) preparation administered orally before D-glucose
      (2g/kg) loading the significant elevation of serum IN levels and improvement of
      impaired glucose tolerance (IGT) in STZ-diabetic mice. Thus, these findings
      suggest that effective oral administration of new In.Cin-Phe derivative
      preparations with dosage form design, such as enteric coating form, may become
      feasible in diabetic patients.

PMID- 8996842
TI  - [Pathophysiological study on the mucosal defense system of genetically obese
      Zucker rats].
AB  - The obese Zucker rat is an animal model of genetically inherited obesity
      demonstrating remarkable hyperphagia. In the present study, to try to clarify the
      relationship between obesity and gastric function including gastric mucosal
      integrity, the gastric acid secretion, emptying, and mucosal resistance against
      ulcerogenic agents were compared in lean and obese Zucker rats. Male lean and
      obese Zucker rats were housed at 25 degrees C under 12-hr/12-hr lighting cycle
      (on at 7:00 AM). The gastric acid output of obese Zucker rats was markedly
      smaller than that of lean Zucker rats, whereas there was no significant
      difference in gastric emptying in both groups. The degree of mucosal lesion
      formation induced by ulcerogenic agents was assessed by measuring the total
      length of all mucosal lesions observed (ulcer index; mm). The intragastric
      administration of indomethacin (20 mg/kg) produced hemorrhagic mucosal lesions in
      both lean and obese groups of Zucker rats, but the ulcer index was remarkably
      smaller in obese Zucker rats than that of their lean littermates (5.2 +/- 1.2 mm
      vs. 17.5 +/- 3.5 mm, mean +/- SEM, P < 0.01). In addition obese Zucker rats
      exhibited stronger resistance against the intragastric challenge of absolute
      ethanol (1 ml/rat), a necrotizing agent, with its ulcer index being 8.5 +/- 2.7
      mm, compared with lean Zucker rats whose ulcer index was 26.4 +/- 5.4 mm (P <
      0.01). The bilateral subdiaphragmatic vagotomy decreased both gastric acid
      secretion and the ulcer index of indomethacin-induced gastric injury observed in
      both obese and lean Zucker rats, whereas there was no significant difference in
      the ulcer index of ethanol-induced gastric injury. These results suggest that
      obese Zucker rats exhibit enhanced resistance against ulcerogens and decreased
      acid output. It is also speculated that the vagal system might be involved in
      inhibition of acid secretion and formation of indomethacin ulcers in obese Zucker
      rats.

PMID- 8996843
TI  - [The new laser Doppler velocimetry for the measurement of retinal circulation and
      its clinical application].
AB  - We developed a new laser Doppler instrument to measure retinal blood flow. This
      instrument is equipped with an eye tracking system, which maintains the laser
      beam on the retinal vessel, thus enabling the measurement of patients with poor
      visual acuity and poor fixation. In diabetic patients even those without
      retinopathy, the retinal blood flow decreased compared to the control subjects.
      This was mainly the result of decreased retinal blood speed and no significant
      change in the arterial diameter. In diabetic patients requiring panretinal
      photocoagulation, we studied the regional changes in retinal blood flow following
      superior or inferior half fundus argon laser treatment, which produced a
      significant retinal blood flow decrease only in the treated area. We also studied
      the retinal circulatory changes in retinal branch vessel occlusion. In retinal
      branch view occlusion, the blood flow in arteries supplying the affected lesion
      showed 80-90% decrease compared to the arteries supplying the unaffected region.
      In retinal branch artery occlusion, the retinal blood flow in occluded arteries
      showed 40-50% decrease compared to the non-occluded arteries. In one patient with
      retinal branch vein occlusion in whom we measured the retinal blood flow over 18
      months, the blood flow increased with the development of collateral vessels. The
      results showed that retinal circulatory abnormalities can be also evaluated
      quantitatively during the course of retinal vascular occlusive disease by our
      newly developed laser Doppler instrument, which proved that this instrument is a
      clinically very useful tool.

PMID- 8996844
TI  - Expression of differentiation antigens and adhesion molecules on CD34+ cells in
      peripheral blood and bone marrow after chemotherapy followed by administration of
      granulocyte colony stimulating factor.
AB  - The expression of differentiation antigens (D/As) and adhesion molecules (A/Ms)
      was studied on CD34 positive (CD34+) cells in peripheral blood (PB) and bone
      marrow (BM) of patients treated with myelosuppressive chemotherapy followed by
      granulocyte colony-stimulating factor (G-CSF) administration (CT/G-CSF). CD33
      positive rates of PB and BM CD34+ cells were significantly higher in the patients
      than those in the normal controls. CD49d positive rate of PB CD34+ was
      significantly lower than that of BM CD34+ cells in both the patients and the
      normal controls, and this decreased expression of CD49d on PB CD34+ cells was
      larger in the patients than in the normal controls. CD117 positive rate was
      significantly lower in PB CD34+ cells of the patients than that of their BM CD34+
      cells and PB CD34+ cells of the normal control. These results suggested that more
      mature progenitor cells increased in the patients' PB and BM after CT/G-CSF, and
      that the decreased expression of CD49d played an important role on
      peripheralisation of CD34+ cells even in steady state, and the decreased
      expression of CD117 was related with the mobilization of CD34+ cells after CT/G
      CSF. CT/G-CSF decreased the expression of CD117 and enhance the decrease of CD49d
      expression on PB CD34+ cells. These changes appeared to be involved in the
      mobilization mechanism of hematopoietic progenitor cells from BM into PB after
      CT/G-CSF.

PMID- 8996845
TI  - [Study of androgen receptor expression and neuronal vulnerability in X-linked
      spinal and bulbar muscular atrophy].
AB  - X-linked spinal and bulbar muscular atrophy (SBMA), a rare adult onset form of
      motor neuron disease, is clinically characterized by slowly progressive muscle
      weakness and atrophy, and endocrinopathy such as gynecomastia, testicular atrophy
      and oligospermia. Androgens are known to play an important role in motor neuron
      growth, development and regeneration. The genetic mutation of androgen receptor
      (AR) gene in SBMA has been disclosed and thought to lead to degeneration of lower
      motor neurons. However, the mechanism of neuronal death and the basis for the
      regional specificity of neuropathology observed in SBMA are not clear. At first,
      we proved the existence of androgen receptor (AR) in the motor neurons of the rat
      spinal cord by the immunohistochemical stain and Western blotting. The
      possibility that AR protein in spinal cord is expressed in tissue-specific form
      is proposed, being different from other androgen-dependent tissue. Northern
      blotting data showed that AR is expressed in not only rat spinal cord but also
      cerebrum and cerebellum, which are spared in SBMA. Then, specimens from 2 SBMA
      patients were examined and compared with those from normal controls (n = 4). AR
      was widely expressed in central nervous system. Anterior horn cells, which are
      severely affected in SBMA, were stained intensely. Even the remaining atrophic
      motor neurons in SBMA had AR. To our interest, the neurons of cranial nerves III,
      IV, VI, dentate nucleus, posterior horn and Onufrowicz nucleus etc., which are
      spared in SBMA, contained AR moderately. These data did not show any difference
      between SBMA and controls. Our immunohistochemical study showed that not only the
      neurons affected in SBMA but the unaffected in this disease process express AR.
      The question why motor neurons are selectively involved in SBMA if AR is present
      in almost neurons should further be clarified.

PMID- 8996846
TI  - Differentiation of inodilatory responses by non-invasive measures of
      cardiovascular performance in healthy man.
AB  - The cardiovascular responses to various inodilatory interventions were
      investigated noninvasively in healthy man by monitoring heart rate (HR), blood
      pressure (SBP/DBP, according to Korotkoff I and IV criteria), systolic time
      intervals (PEP, VET and QS2) and impedance cardiographic estimates of stroke
      volume (SV) and cardiac output (CO). The following inodilatory interventions were
      evaluated and compared: the i.v. infusion of adrenaline (1 microgram/min), the
      i.v. infusion of isoprenaline (1 microgram/min) with and without pretreatment
      with 100 mg talinolol (a beta 1-selective beta-adrenoceptor antagonist), the p.o.
      administration of 1200 mg celiprolol (a beta 1-adrenoceptor antagonist with
      ancillary beta-adrenergic agonistic properties at the chosen dose level), the
      p.o. administration of 0.4 mg bimakalim (a K+ channel activator without direct
      cardiac effect) with and without pretreatment with 5 mg bisoprolol and the p.o.
      administration of the PDE-III inhibitors meribendan and isomazole. The extent of
      the inodilatory rise of HR, shortening of PEP, rise of SV and CO relative to the
      associated reduction of the calculated total peripheral resistance (TPR) proved a
      powerful tool to differentiate inodilatory properties: adrenaline, isoprenaline
      after beta 1-selective beta-adrenoceptor blockade and celiprolol led to similar
      ancillary adrenaline-like cardiovascular changes relative to the vasodilatation;
      bimakalim led to similar associated changes except for a relatively larger rise
      in HR, which could be blocked by bisoprolol; isoprenaline induced clearly larger
      associated changes, for which HR, VET, and QS2c were particularly sensitive;
      meribendan and isomazole resulted in the largest ancillary changes, characterized
      by a critical shortening of the ejection time VET, so that the rise of CO was
      almost exclusively defined by the rise of HR. These differences could be detected
      and differentiated sufficiently and adequately by HR, SV, CO, TPR, PEP, and VET.
      There seems little value in using more assumptive variables such as HR-corrected
      VETc and QS2c, the Weissler index and the impedance cardiographic Heather index.

PMID- 8996847
TI  - Osteomalacia during rifampicin and isoniazid therapy is rare in Hong Kong.
AB  - Prolonged therapy with rifampicin and isoniazid can cause vitamin D deficiency or
      osteomalacia, particularly in patients with marginal vitamin D stores. In the New
      Territories East of Hong Kong, there were at least 1,526 new cases of
      tuberculosis over a 14-month period in 1994-1995. Any severe cases of
      osteomalacia were expected to be hospitalized in the sole general teaching
      hospital of the region. However, among all the general medical patients with one
      of their discharge ICD codes being 268 (vitamin D deficiency) or 275 (disorders
      of mineral metabolism), none had osteomalacia due to rifampicin and isoniazid
      chemotherapy. Thus, this complication appears to be rare in Hong Kong whose
      residents generally have a higher vitamin D status than those of the U.K.

PMID- 8996848
TI  - Mean difference vs. variability reduction: tradeoffs in aggregate measures for
      individual bioequivalence. FDA Individual Bioequivalence Working Group.
AB  - Aggregate criteria for individual bioequivalence allow a tradeoff between
      difference in average bioavailability and reduction in within-subject
      variability. That is, a large difference in the average bioavailability between a
      test and a reference formulation can be offset by a sufficient reduction in
      variability of the test formulation. This offset could allow the test formulation
      to pass many individual bioequivalence criteria. We have identified 4 possible
      approaches for dealing with this tradeoff issue: say "No problem," since a
      reduction in variability is desirable; use disaggregate criteria; use general
      weighted forms of the individual bioequivalence criteria that weight the variance
      terms; and change the acceptable upper limits to reduce the impact of scaling to
      the reference formulation's within-subject variability. A dataset with a 14%
      increase in average bioavailability and a 48% reduction in within-subject
      standard deviation is used as an example of these issues.

PMID- 8996849
TI  - Sulthiame-associated mild compensated metabolic acidosis.
AB  - Sulthiame is effectively used in the treatment of benign and symptomatic focal
      epilepsy in children. Hyperventilation as a symptom is a well known adverse
      effect of the drug. Alterations of the acid-base equilibrium have been described
      for the drug, however, very infrequently only in adults without a detailed
      evaluation of the disorders status. The case presented here demonstrates a mild
      compensated metabolic acidosis in a child which, for the first time, is described
      using the methods of complete blood gas and electrolytes analysis.

PMID- 8996850
TI  - Parametrization by nonlinear regression analysis of the active acid metabolite of
      ebastine using different weighting methods.
AB  - The study of the analytical error function has been applied to evaluate the
      pharmacokinetics of ebastine active acid metabolite after a single oral dose of
      10 mg of metabolite in 6 healthy volunteers. Plasma concentrations were measured
      using an automated solid phase extraction method. The analytical method was fully
      validated and the function of the analytical error subsequently determined. The
      parametric approach was performed by nonlinear regression analysis comparing the
      results obtained after the application of different weighted least square methods
      including the homoscedastic method (W = 1) and heteroscedastic methods using
      weights of 1/C, 1/C2 and the inverse of the concentration variance calculated
      through the function of the analytical error. The results obtained in the study
      showed no influence of the different weighting methods used on the estimation of
      the pharmacokinetic parameters of ebastine acid metabolite.

PMID- 8996851
TI  - Perioperative pharmacokinetics of piperacillin during liver transplantation.
AB  - There have been few evaluations of the perioperative pharmacokinetics of
      antibiotics. Piperacillin (PPR) is a widely prescribed ureidopenicillin of
      established efficacy against enterobacteria and P. aeruginosa. The serum
      pharmacokinetics and perioperative safety of PPR were evaluated in 8 patients
      hospitalized for an orthotopic liver transplantation. The subjects were given a
      60 mg/kg infusion of PPR once every 8 hours. PPR was assayed by HPLC and data
      were analyzed by a noncompartmental method. There were no adverse events during
      surgery. It seems that kinetics of PPR showed no variation during the anhepatic
      period. However, transplants notably modified the kinetics of PPR in comparison
      with data previously published in healthy volunteers. Trends were as follows:
      flattening of Cmax and prolongation of T1/2 (2.2 h vs 0.92 h). This phenomenon
      seems to be due to a marked increase in V(area) (44.0 1 vs 16.2 1) while C1 were
      similar. The increase in V(area) is probably the combined results of multiple
      factors including blood loss, vascular filling, combined prescription of
      vasoactive drugs, and, obviously, the surgical procedure itself. Concentrations
      of PPR were after 4 hours below (i.e. 5/8 patients) the MIC of P. aeruginosa
      (i.e. < or = 16 micrograms/ml). From 6 hours onwards antibacterial cover was
      insufficient against the majority of enterobacteria (i.e. < or = 8
      micrograms/ml). This inadequate protection included the critical anhepatic
      period. Measured concentrations achieved by the initial dosage regimen were
      compared to those obtained by simulation using modified dosing pattern in order
      to ensure circulating levels constantly of 16 micrograms/ml or more. This leads
      to a suggested modified dosage pattern in which PPR would be given as 1 dose of
      60 mg/kg every 4 hours. Under these conditions the expected concentrations should
      be constantly over 16 micrograms/ml and any risk of systemic accumulation is
      excluded.

PMID- 8996852
TI  - Treatment of acute biliary tract infections with ofloxacin: a randomized,
      controlled clinical trial.
AB  - The combination of penicillin with an aminoglycoside has been recommended as an
      initial treatment of choice for patients with acute infections of the biliary
      tract. However, many patients have incidence of renal problems and for this
      reason aminoglycosides must be avoided. Newer antimicrobial agents with lesser
      nephrotoxic effects will be tried. We, therefore, performed a prospective,
      randomized trial of ofloxacin, a new quinolone and ceftriaxone in patients with
      acute biliary tract infections. Fifty-two patients with severe biliary tract
      infections (cholecystitis and cholangitis) were randomly assigned to receive
      either ofloxacin (n = 28) or ceftriaxone (n = 24). The 2 groups receiving
      antibiotics were similar with respect to all clinical and laboratory parameters.
      Bacteria were documented in 48% of patients in the ofloxacin group and in 46% in
      the ceftriaxone group. The percentage of patients with a clinical cure or
      significant improvement was the same in the 2 groups. No significant difference
      was noted between the 2 treatment groups with respect to drug toxicity. These
      data suggest that intravenous ofloxacin followed by oral administration is an
      effective and safe single drug for the therapy of patients with acute biliary
      tract infections.

PMID- 8996853
TI  - Pharmacokinetic characteristics of a new liquid sustained-release formulation of
      theophylline designed for the elderly and children: microcaps as sachet.
AB  - A new sustained-release theophylline formulation was especially designed for the
      elderly and children. Microcapsules of theophylline, administered as a suspension
      in water, proved to be a suitable dosage form for a clientele with impaired or
      difficult deglutition. Pharmacokinetic characteristics of 2 batches at the lower
      (T1) and the upper (T2) in vitro dissolution specification range of this new
      formulation and a pellet formulation (R) as a comparator were evaluated in an
      open, randomized, 3-way, multiple-dose, crossover study design with an asymmetric
      dosage regimen of 400 mg and 200 mg theophylline. Smooth and safe plasma
      concentrations with a high and long-lasting plateau were achieved with this new
      formulation. Plateau times which are independent of the asymmetric dosage regimen
      ranged from 16.4 hours (T1) to 13.8 hours (T2) and could therefore span
      sufficient time of the dosage interval. Maximum serum levels of 9.6 micrograms/ml
      and 10.0 micrograms/ml were attained 6.6 and 6.1 hours after dosing of T1 and T2,
      coinciding perfectly with the time of the critical morning dip at 2-4 a.m. With a
      nocturnal excess of 15.5% (T1) and 17.9% (T2) this circadian-tailored asymmetric
      dosage regimen proved to take into account the chronopathology of asthma and the
      chronopharmacokinetics of theophylline sustained-release preparations.
      Bioequivalence of all 3 formulations versus each other with regard to rate
      (Cmaxss) and extent (AUC(tau)ss) of absorption could be established for the 2
      batches at the upper and lower in vitro specification range and for both batches
      of the new formulation compared to the reference. All in all, safety and efficacy
      of this new liquid prolonged-release theophylline could be established.
      Furthermore, in vitro specifications could be justified according to current EU
      guidelines.

PMID- 8996854
TI  - Bioavailability and pharmacokinetic properties of 2 sustained-release
      formulations of diclofenac sodium, Voltaren vs inflaban: effect of food on
      inflaban bioavailability.
AB  - In this study, in vitro characterization, bioavailability and pharmacokinetics of
      2 different sustained-release diclofenac sodium dosage forms were compared,
      Voltaren (100 mg tablets), manufactured by Ciba-Geigy and Inflaban (100 mg
      enteric-coated tablets), manufactured by the Arab Pharmaceutical Manufacturing
      Company. The in vitro results demonstrated a faster rate of dissolution for
      Inflaban as compared to Voltaren, but both products exhibited a sustained-release
      pattern. The bioavailability study was conducted on 20 healthy male subjects who
      received a single oral dose (100 mg) of each product according to a randomized 2
      way crossover design. Blood samples were obtained over a 26-hour period, and drug
      concentrations were determined by an HPLC method. Concentration time profiles
      revealed a sustained-release pattern for both products. The Tlag for Voltaren was
      0.8 +/- 0.2 h, significantly shorter than for Inflaban (1.7 +/- 0.2 h) indicating
      a faster rate of absorption from the upper gastrointestinal tract. The Cmax
      obtained with Voltaren was significantly higher than that obtained with Inflaban
      (1,161 +/- 102 and 799 +/- 83, respectively). With respect to Tmax and AUC0-26h
      parameters, both products were not found to be statistically different. Tmax for
      Voltaren and Inflaban was 4.2 +/- 0.5 and 4.5 +/- 0.4 h, respectively, whereas
      AUC0-26h values for both products were 5,423 +/- 562 and 5,237 +/- 520 ng x h/ml,
      respectively. It is believed that the observed differences between Voltaren and
      Inflaban are mainly due to the fact that Inflaban is designed as an enteric
      coated tablet form, with a core tablet having different sustained-release
      behavior. In addition, the effect of food on the bioavailability of Inflaban was
      evaluated in randomly selected 6 male volunteers. Our results revealed that,
      following light and heavy meals, the AUC0-30 and Cmax were minimally affected by
      food whereas a significant increase in Tmax and Tlag as compared to fasting
      conditions was observed.

PMID- 8996855
TI  - Steroidal glycosides from the fresh stem of Stephanotis lutchuensis var. japonica
      (Asclepiadaceae). Chemical structures of stephanosides K-Q.
AB  - The structural elucidation of seven related oxypregnane-oligoglycosides
      stephanosides K (1), L (2), M (3), N (4), O (5), P (6), and Q (7) from the fresh
      stem of Stephanotis lutchuensis var. japonica (Asclepiadaceae) was achieved
      through on a detailed study of their high-field 1H- and 13C-NMR spectra. The
      results show that all the sugars are beta (1-->4)-linked. The aglycones of
      stephanosides K, M, and O, and stephanosides L, N, and P were identified as 12-O
      cinnamoyl-20-O-(E)-2-methyl-2-butenoyl, and 12-O-cinnamoyl-20-O-nicotinoyl
      derivatives of (20S)-pregn-6-ene-3 beta,5 alpha,8 beta,12 beta,14 beta,17 beta,20
      heptaol, respectively. The aglycone of stephanoside Q was 12-O
      cinnamoyldeacetylmetaplexigenin (kidjoranin).

PMID- 8996857
TI  - Forskolin derivatives. I. Synthesis, and cardiovascular and adenylate cyclase
      stimulating activities of water-soluble forskolins.
AB  - Water-soluble forskolin and 7-deacetylforskolin derivatives with an aminoacetyl,
      a 3-aminopropionyl, or a 4-aminobutyryl group at the 6- or 7-position were
      prepared, and their positive inotropic as well as vasodilative activities were
      evaluated in anesthetized dogs. 7-Deacetylforskolin (2) and 7-deacetyl-1
      silylforskolin (6) were converted to the corresponding 7-chloroacylderivatives
      (3, 7, 10), which were reacted with amines to obtain 7-aminoacyl-7
      deacetylforskolins (4a-f, 9a, b, 11). The 7-acyl substituents migrated to the 6
      position with sodium hydroxide in acetonitrile-water to afford 6-aminoacyl-7
      deacetylforskolins (12a-f). The 7-position of 12a, d-f was selectively acetylated
      with acetyl chloride to obtain the corresponding 6-aminoacylforskolins (13a-d).
      Among the 6-aminoacylforskolins, 6-(3-dimethylaminopropionyl)forskolin (13b) and
      6-(4-dimethylaminobutyryl)forskolin (13d) exhibited potent positive inotropic and
      vasodilative activities comparable to those of forskolin (1). The activities of
      13b and 13d were approximately ten times more potent than those of 7-aminoacyl-
      and 6-aminoacyl-7-deacetylforskolins (4a-f, 9a, 12a-c, f). 6
      Dimethylaminoacetylforskolin (13a) and 6-(3-diethylaminopropionyl)forskolin (13c)
      were less potent than 1. The effects of the soluble forskolins on adenylate
      cyclase activity were also examined in vitro. 6-Aminoacylforskolins (13a-d)
      exhibited potent adenylate cyclase-stimulating activity, comparable to that of 1.

PMID- 8996856
TI  - Chemical composition of the cell wall of lactic acid bacteria and related
      species.
AB  - In order to examine the relationship between biological activities and the cell
      wall content, the murein type and the teichoic acid of the cell wall from five
      strains of bacteria were studied. Two of these Lactobacillus casei CRL 431 and L.
      acidophilus CRL 730, are used in a commercial fermented milk (BIO MILK), which is
      believed to be beneficial for health. The other strains, Lactococcus lactis CRL
      526, Pediococcus pentosaceus CRL 923 and Propionibacterium acidipropionici CRL
      1198 were included in order to compare the cell wall structures of active and
      inactive strains. A method was designed to confirm the amino acids of the
      peptidoglycan in impure substrates. Four of the studied strains, L. casei, L.
      acidophilus, L. lactis and P. acidipropionici, contained glycerol teichoic acids.
      L. casei, L. acidophilus, P. pentosaceus and L. lactis contained A4 alpha type
      murein, while P. acidipropionici contained A3 gamma type. The capacity of orally
      administered peptidoglycans of the studied strains to stimulate phagocytosis by
      mouse peritoneal macrophages was analyzed. Only the PG of L. casei showed this
      activity. No differences were observed between active and inactive strains with
      respect to the chemical composition of the peptidoglycan. Therefore the
      biological activity is unlikely to be due to the peptidoglycan structure.

PMID- 8996858
TI  - Synthetic studies of vitamin D analogs. XXII. Synthesis and antiproliferation
      activity of putative metabolites of 1 alpha, 25-dihydroxy-22-oxavitamin D3.
AB  - As putative metabolites of 1 alpha,25-dihydroxy-22-oxavitamin D3 (OCT), 24
      hydroxylated OCT in 24(R) and 24(S) forms, 24-ketoOCT, 26-hydroxylated OCT in
      25(S) and 25(R) forms, pentanorOCT and pentanor-ketoOCT were synthesized from the
      steroidal 20(S)-alcohol. Their antiproliferation activities towards human
      promyelocytic leukemia cells (HL-60 cells) are also reported. Oxidized
      derivatives at the C-24 position, 24-ketoOCT, 24(R)-hydroxylated OCT and 24(S)
      hydroxylated OCT, showed activities comparable to or slightly weaker than that of
      OCT, while 26-hydroxylated OCT was less active than OCT. Truncated OCT, pentanor
      OCT and pentanor-ketoOCT, were inactive at 10(-7)-10(-10) M.

PMID- 8996859
TI  - Antirheumatic agents. II. Novel methotrexate derivatives bearing an alkyl
      substituted benzene ring.
AB  - Novel methotrexate (MTX) derivatives with either a mono- or dialkyl-substituted
      benzene ring were synthesized and initially tested for in vitro anti
      proliferative activities using human peripheral blood mononuclear cells (hPBMC)
      derived from healthy volunteers and synovial cells (hSC) derived from patients
      with rheumatoid arthritis (RA). Compounds with potent activities were further
      evaluated in an in vivo adjuvant arthritis model. In comparison with MTX, a
      glutamate derivative 3a was more potent as a suppressor of the in vitro cell
      proliferation and the in vivo experimental arthritis, and a homoglutamate
      derivative, 3e, exhibited fairly good activities in vitro and considerable
      activity in vivo in a dose-dependent manner. As expected, 3e did not act as a
      substrate of folylpolyglutamate synthetase (FPGS), and thus did not undergo
      polyglutamation, which is thought to be responsible for side-effects that occur
      during MTX therapy.

PMID- 8996860
TI  - Studies on differentiation inducers. VI. Lignan derivatives from Arctium fructus.
      (2).
AB  - In the previous paper, we reported the differentiation inducing activities of
      lignoids from Arctium Fructus (the fruits of Arctium lappa L., Compositae)
      against mouse myeloid leukemia cells (M1). We reinvestigated the active
      components of this extract and isolated three new dilignans. Furthermore,
      structure modifications were carried out using the most active lignan
      (arctigenin, 1) and its structure-activity relationship was investigated. Its
      aliphatic esters were more effective in inducing the differentiation of M1 cells
      than its aromatic esters. Especially, n-decanoate, which was the most active
      derivative, induced more than half of the M1 cells into phagocytic cells at a
      concentration of 2 microM.

PMID- 8996861
TI  - Metal-containing components in medicinal plants. III. Manganese-containing
      components in Theae folium as oral magnetic resonance imaging contrast materials.
AB  - A manganese-containing component from the water-extract of Theae folium (green
      tea) was found to exert an augmentative effect in magnetic resonance imaging
      (MRI) contrast and may possibly be a manganese(II) complex with a pectin-like
      polysaccharide capable of shortening the spin-lattice relaxation time (T1) of
      water protons. Even though only the manganese(II) ion with S = 5/2 is active in
      T1-shortening ability, which should enhance contrast, complexation of this ion
      with the polysaccharide causes a marked increase in its activity. This manganese
      containing pectin-like polysaccharides should prove useful as a low-toxic oral
      gastrointestinal contrast material in MRI.

PMID- 8996862
TI  - In vitro stability and in vivo absorption studies of colloidal particles formed
      from a solid dispersion system.
AB  - We investigated the physicochemical and pharmaceutical properties of a solid
      dispersion (SD) derived from a solution of the poorly water-soluble drug (R)-1
      [2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]-3
      (3-methylphenyl)urea (YM022), hydroxypropylmethylcellulose 2910 (TC-5E) and
      polyoxyethylene hydrogenated caster oil 60 (HCO-60). Colloidal particles produced
      when the SD was dispersed into water had a mean diameter of 160 nm and contained
      67-77% YM022. Powder X-ray diffractometry showed that YM022 existed in the
      colloidal particles in an amorphous state. The particle diameter and YM022
      content remained unchanged during storage for 7 d, confirming that the colloidal
      solution was stable. On oral administration to rats, good absorption was observed
      for both the colloidal solution prepared immediately before and the sample stored
      for 7 d before administration. Thus, the stability of this colloidal solution of
      SD was confirmed by in vitro storage tests and by in vivo absorption experiments
      in rats.

PMID- 8996863
TI  - Synthesis of isomelamines and isocyanurates and their biological evaluation.
AB  - The reaction of cyanogen bromide (1) with primary amines (2a-p), including
      arylmethylamines (2l-p), gave the corresponding cyanamides (3a-p). Trimerization
      of 3a-p gave 1,3,5-trisubstituted 2,4,6-triiminohexahydro-1,3,5-triazines
      (isomelamines) (4a-p), which were treated with hydrochloric acid to give the
      corresponding 1,3,5-trisubstituted 2,4,6-trioxohexahydro-1,3,5-triazines
      (isocyanurates) (5a-c, f) and 1,3,5-trisubstituted 2-imino-4,6-dioxohexahydro
      1,3,5-triazines (5b'-e'). Biological evaluation of 4a-p, 5a-c,f, and 5b'-e' was
      carried out, and some of these compounds showed bronchodilator and positive
      inotropic activities.

PMID- 8996864
TI  - Studies on the synthesis and structure-activity relationships of 2-(2
      functionalized pyrrolidin-4-ylthio)-1 beta-methylcarbapenems.
AB  - A series of new carbapenem derivatives, which have a pyrrolidin-4-ylthio group
      substituted with a hydroxyalkyl or carbamoyl group at the 2' position as the C-2
      side chain, have been prepared. The antibacterial activity and the stability to
      renal dehydropeptidase-I of these compounds were investigated, and the structure
      activity relationships were studied. Among these new carbapenems, (1R,5S,6S)-2
      [(2S,4S)-2-?(2-hydroxy)ethylmercaptomethyl?pyrroli din-4 -ylthio]-6-[(1R)-I
      hydroxyethyl]-1-methyl-1-carbapen-2-em-3- carboxylic acid (1a) showed the most
      potent and well balanced activity and was selected as a candidate for further
      evaluation.

PMID- 8996866
TI  - Effects of the structures of polyoxyethylene alkyl ethers on uptake of butyl p
      hydroxybenzoate by Escherichia coli and its antibacterial activity.
AB  - The effects of the structures of non-ionic surfactants on the uptake of butyl p
      hydroxybenzoate (BP) into Escherichia coli cells and its antibacterial activity
      were systematically studied using polyoxyethylene alkyl ethers (PAEs) possessing
      various oxyethylene and hydrocarbon chain lengths. The uptake of BP into
      bacterial cells in an aqueous PAE solution was proportional to free BP in an
      aqueous phase, depending on the structures of PAEs. The antibacterial activity of
      BP decreased in the presence of PAEs, whereas it was greater than that
      anticipated from free BP. However, only PAE with 12 carbons in the hydrophobic
      group caused unusual increases in the uptake and antibacterial activity of BP,
      and the surfactant was more extensively incorporated into bacterial cells,
      differing from other PAEs, which were much less incorporated. The PAEs were thus
      concluded to increase the susceptibility of bacteria against BP due to direct
      interactions with the cells. Particularly, the PAE with 12 carbons in the
      hydrophobic group, which penetrated abundantly into the cells, might result in an
      increase in the fluidity of the cellular lipid matrix and a decrease in the
      resistance of drug permeation.

PMID- 8996865
TI  - Synthesis and antiviral activity of 6-chloropurine arabinoside and its 2'-deoxy
      2'-fluoro derivative.
AB  - 6-Chloropurine arabinoside (3a) was obtained by treatment of the 2'-O-acetylated
      congener (2) with ammonia in methanol. The 3',5'-di-O-tritylated riboside (6) was
      allowed to react with diethylaminosulfur trifluoride (DAST) in the presence of
      pyridine to give the 2'-deoxy-2'-fluoroarabinoside (7), from which 6-chloro-9-(2
      deoxy-2-fluoro-beta-D-arabinofuranosyl)purine (3b) was obtained. The antiviral
      effects of 3a and 3b were assayed against several DNA and RNA viruses. Only 3a
      displayed potent activity against varicella-zoster virus (VZV). This antiviral
      activity was dependent on phosphorylation by the VZV-induced thymidine kinase
      (TK). Compound 3a showed moderate activity against other DNA viruses, herpes
      simplex type 1 (HSV-1) and type 2 (HSV-2), and vaccinia virus. They were equally
      active against TK- and TK+ strains of HSV-1, which suggests that the HSV-1
      encoded TK does not play a role in the anti-HSV-1 activity. No activity was noted
      with any of the compounds against various RNA viruses, including human
      immunodeficiency virus, at subtoxic concentrations.

PMID- 8996867
TI  - Relative effectiveness coefficient: a quality characteristic of toothpastes
      containing active components.
AB  - It has been proposed that the parameter of relative effectiveness coefficient
      (REC) be used for the qualitative assessment of toothpastes containing active
      ingredients. REC is the ratio between the concentration of the active component
      in water eluates obtained after three minutes and adequately prolonged (up to the
      reaching of equilibrium state) dispersion of the toothpaste in distilled water at
      a 1:4 ratio (condition simulating the use of toothpaste in the oral cavity). The
      change in REC after storage following its production, as well as testing the
      toothpaste stability at high and low temperatures, provides an evidence for
      deviations in its quality. REC was applied for the assessment of toothpastes
      containing 0.5% zinc citrate as an active ingredient.

PMID- 8996868
TI  - Microbiological contamination of carcasses related to hygiene practice and
      facilities on slaughtering lines.
AB  - The purpose of the study was to investigate the association between the hygienic
      practice of slaughterhouse workers and the microbiological contamination level of
      carcasses. In 5 Finnish slaughterhouses the workers' hygienic practice was
      observed and the carcasses were sampled by the swabbing method. The overall means
      (log10 cfu cm-2) of the aerobic plate count in pork and beef carcasses were 3.23
      and 2.65, respectively. Hygienic practice was found to be associated with the
      carcass contamination level, especially the disinfection frequency. In those
      slaughterhouses, where the disinfection frequency was low, the contamination
      level of carcasses was high. Designing slaughtering lines so as to make hygienic
      working possible is evidently very important. However, the enforcement of
      hygienic practice, such as the regular disinfection of working tools, is also
      important in reducing the microbiological contamination of carcasses.

PMID- 8996869
TI  - Calcification of intervertebral discs in the dachshund: a radiographic study of
      115 dogs at 1 and 5 years of age.
AB  - The vertebral columns of 115 dachshunds were x-rayed at 1 and 5 years of age.
      This sample represented 5.7% of all dachshunds registered with the Norwegian
      Kennel Club in the period 1986-1988. All dogs were clinically normal at the
      commencement of the study. At 1 year of age calcified intervertebral discs were
      identified in 34 (29.6%) of the dogs and the number of calcified discs in each
      individual varied from 1 to 7 with a mean of 2.7. At 5 years of age calcified
      discs were identified in 66 (57.4%) of the dogs and the number of calcified discs
      in each individual varied from 1 to 11 with a mean of 3.2. Of all dogs in which
      calcified discs were identified at 1 year of age, 33 (97.1%) were found to have
      calcified discs also at 5 years of age. Of 92 calcified discs identified in the
      dogs at 1 year of age, 29 (31.5%) were not calcified 4 years later. Of 211
      calcified discs identified in the dogs at 5 years of age, 148 (70.1%) were not
      calcified 4 years before. From 1 to 5 years of age, signs of spinal disease were
      registered in 12 (35.3%) of the dogs in which calcified discs were identified at
      1 year of age, and in 7 (8.6%) of the dogs in which calcified discs were not
      identified at 1 year of age. Of all dogs in which one or more calcified discs had
      disappeared during the study-period, signs of spinal disease were registered in 9
      (75.0%).

PMID- 8996870
TI  - Ultrastructure of bovine ovarian follicles induced to extended growth by
      perioestrous suprabasal progesterone levels.
AB  - The present study was undertaken to determine if a short-term prolonged growth of
      the ovulatory follicle (12 to 18 h after expected time of ovulation), induced by
      progesterone implants, would cause ultrastructural changes in the follicular
      wall. Oestrous behaviour, follicular growth, follicular and blood plasma levels
      of oestradiol-17 beta, progesterone and plasma luteinizing hormone (LH) were
      monitored in heifers oophorectomized at 9 to 12 h (controls) or 36 h after the
      onset of oestrus, in order to sample the pre-ovulatory follicle present. The
      suprabasal plasma progesterone concentrations (approximately 1.2 nmol L-1)
      allowed expression of oestrus at the expected time, but ovulation was delayed
      owing to the absence of a LH-surge. The resulting prolongation of follicle growth
      was associated with mild degenerative changes in the follicle wall, i.e. both
      granulosa and thecal cells presented increased electron density, higher amounts
      of secondary lysosomes and lipid droplets, increased intercellular spaces with
      presence of debris. No signs of luteinization were seen.

PMID- 8996871
TI  - Intrauterine bacterial findings and hormonal profiles in post-partum cows with
      normal puerperium.
AB  - The post-partum intrauterine bacterial flora, prostaglandin release, uterine
      involution and resumption of ovarian activity were studied in 9 Swedish dairy
      cows during the first 8-week period. Uterine involution was monitored by
      transrectal examinations of the reproductive tract 3 times weekly.
      Bacteriological examination was performed from twice weekly uterine biopsies. The
      main PGF2 alpha metabolite (15-ketodihydro-PGF2 alpha) was monitored from twice
      daily blood plasma samples, while morning samples were used for progesterone
      determinations. The cows were assigned to 2 groups: Group I (n = 7) with an
      uncomplicated puerperal period and Group II (n = 2) with signs of intrauterine
      infections. A total of 143 biopsies were collected, of which 129 (90.2%) were
      found to be bacteriologically negative. Thirteen (9.1%) of the remaining 14
      biopsies were bacteriologically positive, while one (0.7%) was probably a
      contamination on a single occasion. The 13 bacteriologically positive biopsies
      belonged to the Group II cows from which 31 isolates contained 6 different genera
      of facultative and obligate anaerobic bacteria. Actinomyces pyogenes along with
      Bacteroides sp. and Fusobacterium necrophorum were found to predominate in a
      mixed flora. The bacteria were rapidly eliminated and disappeared completely from
      the uteri towards the end of the third week post-partum. The average number of
      days required for completion of uterine involution was 21.8 +/- 3.0 for all
      animals. The plasma levels of the PGF2 alpha metabolite were significantly
      elevated for the first 12-18, and 18 and 27 days in Group I and Group II,
      respectively. There was no significant relationship between the duration of PGF2
      alpha release and the time required for completion of uterine involution (p >
      0.05). Progesterone analysis showed resumption of ovarian activity and subsequent
      ovulation in 4 of the 9 cows 44-55 days post-partum. Thus, intrauterine
      infections are not commonly seen in cows with normal calving and comparison
      between the duration of PGF2 alpha release and the time required for completion
      of uterine involution showed insignificant correlation. However, the longer
      duration of PGF2 alpha release recorded in the 2 cows with intrauterine
      infections are related to the increased frequency of infections.

PMID- 8996872
TI  - Unstable stifles without clinical or radiographic osteoarthritis in young goats:
      an experimental study.
AB  - Thirteen young, castrated male goats had instability of one stifle (knee joint)
      created by surgical transection of the cranial cruciate ligament, but did not
      develop any signs of osteoarthritis (OA) in treated joints when confined in
      limited space for 8 months. At the end of the experiment, the instability in the
      stifles had not improved, the joints were normal at radiographic examination,
      there were no signs of inflammation in the synovial membrane or joint capsule,
      and fibrosis in these tissues was not evident. The articular cartilage was normal
      both visually and histologically. This may indicate that the young age of the
      goats and the restricted physical activity on soft floor had prevented the
      expected development of OA in the experimentally operated joints. Synovial fluid
      volumes and proteoglycan concentration were measured in the treated and control
      joints in 6 of the goats. There seemed to be increased quantity of the
      proteoglycan aggrecan in the synovial fluid from the treated joints compared to
      the contralateral joints throughout the course of this study. It was concluded
      that the turnover of aggrecan in the articular cartilage of the treated joints
      may have been increased.

PMID- 8996874
TI  - A long-term study on the health status and performance of sows on different feed
      allowances during late pregnancy. II. The total cell content and its percentage
      of polymorphonuclear leucocytes in pathogen-free colostrum and milk collected
      from clinically healthy sows.
AB  - The main objective of this study was to determine the total cell content, TCC,
      and the percentage of polymorphonuclear leucocytes, PMNLs, in colostrum and milk
      collected from sows during the first 22 days of lactation. The pH-values during
      the same sampling period were also determined. It should be emphasized that all
      the values obtained emanate from bacteriologically negative colostrum and milk.
      The potential influence of different levels of late gestation feeding regimes was
      also evaluated. The TCC-values obtained from milk samples during the first 3
      weeks of lactation and exceeding the designated threshold of 10 x 10(6) cells/ml
      varied between 4% and 21%. Within the TCC-limitation of 10-19.99 x 10(6) cells/ml
      neither the preceding nor the succeeding cell counts exceeded the threshold in
      26.8%. TCC-values above 19.99 x 10(6) cells/ml were preceded and succeeded by
      cell counts below the threshold in 58.8% and 58.8%, respectively. The TCC-levels
      below the threshold of 10 x 10(6) cells/ml, expressed as geometric least square
      means, increased significantly from day 1 to day 3 (1.23 x 10(6) cells/ml versus
      1.86 x 10(6) cells/ml) and decreased thereafter gradually to day 22 (1.38 x 10(6)
      cells/ml). When all values were included, the TCC-values increased in a similar
      pattern from day 1 to day 3 (1.38 x 10(6) cells/ml versus 3.18 x 10(6) cells/ml).
      The value on day 22 of lactation was still on a significantly elevated level
      compared with that of day 1 (2.10 x 10(6) cells/ml versus 1.38 x 10(6) cells/ml).
      The 2 different feeding regimes were not found to influence the TCC-values during
      the first 22 days of lactation. In the whole material the PMNL-values, expressed
      as percentages of the TCC, declined from approximately 60% on day 1 of lactation
      to between 40% and 50% for the remaining sampling period. This decline was
      comparable with the one seen in the cell class below the threshold of 10 x 10(6)
      cells/ml. In the 2 cell classes above 9.99 x 10(6) cells/ml, 78.0% and 88.8% of
      PMNLs on day 1 declined to about 40% on day 22. This might indicate an
      inflammatory response on day 1 but without any detectable bacteriological growth.
      The increase in lactation number, if lactation 1 was compared with the following
      lactations, revealed a significant rise (p < 0.05) in TCC-level and percentage
      level of PMNLs. A stepwise and significant increase in pH-level occurred between
      days 1, 3 and 8 (6.18, 6.56, 7.03) followed by a significant decrease to day 22
      (6.91) when pH-values from milk of all cell classes were included.

PMID- 8996873
TI  - An experimental study on transcutaneous absorption of ethylesters of
      eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in
      pigs.
AB  - Twenty-two pigs with an average weight of 24.2 kg were divided into two groups.
      Five grams of an ointment containing 40% of the n-3 polyunsaturated fatty acids,
      eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) as
      ethylesters, was administered cutaneously to the experimental group and orally to
      the control group twice daily over a 3 day period. Surgical biopsies of
      subcutaneous fat of all 22 pigs were taken before and after the ethylester
      administration period. Blood samples were taken from the jugular vein. Skin
      biopsies were taken after the application period, and the presence of
      pathological features and inter-animal variation were noted. No increase of EPA
      and DHA in subcutaneous fat was found in either group. In the oral group the
      content of EPA had increased in the total plasma lipids on the first day after
      the end of the experiment. It is concluded that a rapid transcutaneous absorption
      of EPA and DHA as ethylesters does not seem to occur in pigs.

PMID- 8996875
TI  - A long-term study on the health status and performance of sows on different feed
      allowances during late pregnancy. III. Escherichia coli and other bacteria, total
      cell content, polymorphonuclear leucocytes and pH in colostrum and milk during
      the first 3 weeks of lactation.
AB  - The objectives of this study were to (1) estimate the clinical status of the
      mammary glands and (2) compare it with the bacteriological findings, the total
      cell content (TCC) and its percentage of polymorphonuclear leucocytes (PMNLs) and
      pH in colostrum and milk secretion of sows on 2 different feeding regimes, high
      versus low, during late pregnancy. The milk samples were collected from both
      agalactia post partum (APP) sows and clinically healthy sows. Sows with a rectal
      temperature exceeding 39.5 degrees C within 48 h after parturition were
      considered to be diseased in APP and treated medically. The sows were sampled on
      days 1, 3, 8 and 22 of lactation during 6 consecutive lactations. Irrespective of
      feeding regimes, 49 out of 77 lactations among the APP sows and 15 out of 96
      lactations among the clinically healthy sows revealed E. coli in pure cultures
      with a concomitant TCC exceeding 10 x 10(6) cell/ml already on the first day of
      lactation. The healthy sows with E. coli infection were denominated as being
      subclinically infected sows. The intensity in growth of E. coli successively
      declined, and the bacteria were finally eliminated between days 3 and 8 of
      lactation. The TCC were 82 x 10(6) cells/ml and 157 x 10(6) cells/ml in the
      clinically and subclinically E. coli infected glands, respectively, on the first
      day of sampling. The TCC declined gradually in both groups of sows, but was still
      higher than in bacteriologically negative milk on day 22 of lactation. The
      percentages of PMNLs were 66% and 79% in clinically and subclinically infected
      glands, respectively, on day 1 of lactation, thereafter decreasing to
      approximately 50% on day 22 of lactation in both groups of sows. In APP sows,
      swelling, reddening and/or soreness were registered in 38 out of 87 mammary
      glands with E. coli mastitis on the first sampling occasion. The TCC in
      bacteriologically negative colostrum and milk collected from APP sows on day 1 of
      lactation was significantly higher, 2.27 x 10(6) cells/ml, when compared with the
      TCC in bacteriologically negative milk secretion from the clinically healthy or
      subclinically infected sows, 1.38 x 10(6) cells/ml versus 1.51 x 10(6) cells/ml,
      respectively. The PMNLs were higher on day 1 in clinically healthy sows, 59.6%,
      than in subclinically infected and APP sows (43.5% and 48.3% respectively). The
      pH in secretion from clinically or subclinically E. coli infected glands (6.57
      versus 6.46) were higher than in bacteriologically negative colostrum samples
      (6.29) from clinically diseased sows on the first day of sampling. On day 22 of
      lactation, pH-values had stabilized on a level of approximately 7.00 in all milk
      samples from earlier bacteriologically positive or negative mammary glands. The 2
      feeding regimes, low versus high, were not found to influence TCC, PMNLs or pH
      except for TCC in bacteriologically negative samples of APP sows (2.69 versus
      3.62). The lactation number influenced the PMNLs in both groups of sows with E.
      coli infected mammary glands, and both the TCC and PMNLs in bacteriologically
      negative colostrum and milk.

PMID- 8996876
TI  - Effects of additional premedication on romifidine and ketamine anaesthesia in
      horses.
AB  - The clinical and cardiorespiratory effects of premedication with acepromazine,
      butorphanol or diazepam in addition to romifidine before induction of anaesthesia
      with ketamine were studied in 6 horses on 4 random occasions. Administration of
      romifidine alone or in combination with butorphanol resulted in an increase in
      arterial blood pressure, accompanied by a significant decrease in heart rate with
      second-degree atrio-ventricular heart block. Induction of anaesthesia with
      ketamine returned the heart rate to baseline value, but the arterial blood
      pressure was significantly increased compared to baseline. Including acepromazine
      in the premedication prevented the hypertension and bradycardia induced by
      romifidine. The respiratory rate was slightly decreased after premedication in
      all groups, but returned to the baseline value after induction of anaesthesia.
      Mild hypercapnia and significant hypoxaemia were observed during sedation and
      anaesthesia, reflecting an impairment of pulmonary function. Premedication with
      acepromazine before sedation with romifidine resulted in a fast induction and
      good anaesthesia. Inclusion of butorphanol in the premedication resulted in
      individual variation in the quality of induction and anaesthesia. Addition of
      diazepam to the sedation with romifidine resulted in good muscle relaxation with
      a smooth induction and maintenance of anaesthesia and an increased time before
      the horses responded to noxious stimuli, compared with romifidine and ketamine
      anaesthesia. All horses reached a standing position at the first attempt, but
      horses premedicated with diazepam in combination with romifidine showed mild
      ataxia after recovery.

PMID- 8996877
TI  - Serological characterization of Actinobacillus pleuropneumoniae biotype 1 strains
      antigenically related to both serotypes 2 and 7.
AB  - Nine Danish Actinobacillus pleuropneumoniae biotype 1 isolates were shown by
      latex agglutination and indirect haemagglutination to possess capsular
      polysaccharide epitopes identical to those of serotype 2 strain 1536 (reference
      strain of serotype 2) and strain 4226 (Danish serotype 2 strain). Immunodiffusion
      confirmed the antigenic relationship with serotype 2 and further demonstrated an
      antigenic relationship with strain WF83 (reference strain of serotype 7). SDS
      PAGE with LPS from strains 1536, 4226, WF83 and strain 7317 (representative of
      the 9 isolates examined) showed that strains WF83 and 7317 had an identical
      smooth ladder pattern whereas LPS from strains 1536 and 4226 showed a distinctly
      different pattern. The antigenic similarities of the LPS of strains WF83 and 7317
      were confirmed by immunoblots using rabbit or pig antisera prepared against the 3
      strains. No antigenic similarities in the LPS of strains 1536 and 7317 were
      revealed. Since an antigenic determinant specific for the 9 isolates could not be
      demonstrated with the methods used, the strains are proposed to be designated
      K2:O7.

PMID- 8996878
TI  - First record of Giardia in cattle in Denmark.
AB  - Faecal samples from asymptomatic dairy cows and calves from a farm on the Island
      Falster, Denmark, were examined by a sucrose gradient flotation technique.
      Giardia cysts were found in 7.6% of the 92 samples, and estimated cyst excretion
      rates ranged from 50-200 cysts per gram faeces. Given that Giardia has the
      potential to cause clinical disease in cattle and to be transmitted to other
      animal species and humans, finding the parasite in cattle may be of major
      epidemiological significance. Future work should focus on elucidating the
      pathogenicity, transmission patterns and the genetic structure of Giardia
      populations in cattle in Denmark.

PMID- 8996879
TI  - Recovery rate and quality of embryos from mares inseminated at the first post
      partum oestrus.
AB  - The pregnancy rate is lower in mares inseminated at the first post-partum (p.p.)
      oestrus (40-50%) compared with pregnancy rates in subsequent oestrous cycles (55
      65%). The causes of the lowered pregnancy rate are not fully understood. The aim
      of the present study was to examine if embryonic defects could be one of the
      reasons for lowered pregnancy rate. A total of 23 p.p. and 14 non-lactating
      control mares were flushed 7 days after detection of ovulation. Embryo recovery
      rate was 48% and 71% in p.p. and control mares, respectively (p = 0.16). Embryos
      were photographed, measured, graded and stained with fluorescein diacetate to
      assess their viability. Thereafter embryos were bisected and stained with Hoechst
      33342 to count the cell nuclei. Embryos in both groups were equally viable and
      the cell numbers were not significantly different. According to morphological
      evaluation all embryos were classified as excellent or good. Embryos aged 7.3 to
      7.6 days (+/-0.25 days) were smaller in the p.p. group than in the control group
      (p < 0.05). Forty-seven (9/19) and 8% (1/13) of the uterine swabs, taken before
      the first insemination, yielded bacteria and neutrophils in p.p. and control
      mares, respectively. The amount of neutrophils and/or bacteria had no
      statistically significant effect on embryo recovery rate (p > 0.10). Recovery of
      embryos was not related to histological findings in uterine biopsies taken after
      embryo recovery. Embryo recovery rate in p.p. mares (48%) was similar to
      previously reported foal heat pregnancy rates (40-50%). Hence, early embryonic
      death in utero would not be the most likely reason for lowered pregnancy rate in
      mares inseminated at the first p.p. oestrus. Sperm transport and oviductal
      conditions by the time of the first p.p. oestrus would need to be studied to
      clarify the role of fertilisation failure as the cause of lower pregnancy rate in
      mares inseminated at foal heat.

PMID- 8996880
TI  - Cataract development in Atlantic salmon (Salmo salar L) in fresh water.
AB  - Irreversible bilateral cataracts were diagnosed by slit-lamp biomicroscopy in 178
      of 200 farm-raised Atlantic salmon (Salmo salar L) fed a standard diet over a
      five-month period. Initial changes were anterior polar opacities, progressing to
      involve both the anterior and posterior cortex before changes in the lens nucleus
      were seen. The lens changes were recorded and given scores according to the
      severity of the cataracts. At each of 3 samplings, after 2, 4 and 5 months, 200
      fish were measured, weighed and examined by slit-lamp biomicroscopy. At all 3
      samplings, there was a significant correlation between body length and both
      cataract incidence and cataract severity. There was also a significant
      correlation between body weight and cataract incidence and severity for the 2
      last samplings. There was a significant correlation between K-factor as a measure
      of the shape of the fish, and both cataract incidence and severity, at all 3
      samplings. Evaluation of specific growth rate in the periods between the
      examinations showed that the rapidly-growing fish were most susceptible to
      cataract formation. After cataract developed, however, the growth rate slowed.
      Follow-up examination of severely affected fish 3 months after transfer to sea
      water showed a normal cortical zone in the periphery of the lens in 24 out of 28
      fish.

PMID- 8996881
TI  - Effect of timing of frozen semen insemination on pregnancy rate in mares.
AB  - Thirty-four mares were inseminated with frozen semen from one stallion during 2
      oestrous cycles, every 48 h until ovulation took place and within 12 h after
      ovulation. Semen was frozen using the Colorado method. The insemination dose was
      from 200 to 400 x 10(6) progressively motile spermatozoa. Ovaries were examined
      every 12 h to determine time of ovulation. Examination for pregnancy was carried
      out using ultrasonography, 15 days after ovulation. Thirty-five per cent of mares
      inseminated < 24 h and 23% of mares inseminated between 24-48 h before ovulation
      were pregnant (p = 0.388). The pregnancy rate in all mares inseminated before
      ovulation was 30%. In the mares inseminated within 12 h of ovulation, it was 18%
      (p = 0.253). Younger mares (aged 4-10 yr) had a higher pregnancy rate (59%) than
      older mares (aged 11-15 yr) (23%), but the difference was not statistically
      significant (p = 0.057).

PMID- 8996882
TI  - A sperm midpiece defect in a Hereford bull with variable semen quality and
      freezability.
AB  - A midpiece sperm defect with a frequency of 25-35% in ejaculates obtained from a
      Hereford bull with a 60 d non-return rate of 76.4% after careful pre- and post
      freeze semen selection was studied in light microscope and by transmission
      electron microscopy. The defect consisted in a folding and coiling of the distal
      midpiece characterized by disorganization and irregularity of mitochondria
      surrounding the axial fiber bundle, combined with retraction of doublet fibers
      and dislocation and fracturing of these elements and the corresponding dense
      fibers. Based on examination of the spermatogenic epithelium it was concluded
      that the alterations in the axial fiber bundle were secondary to those in the
      mitochondrial sheath. The abnormality appeared to be related to the "Dag-like"
      defect earlier observed in different breeds.

PMID- 8996883
TI  - The tradition of animal disease control in the Nordic countries compared to the
      rest of Europe.

PMID- 8996884
TI  - Benefit-cost analysis and simulation models: tools in the decision making process
      whether starting a vaccination programme or not.

PMID- 8996885
TI  - Effect of vaccination against Aujeszky's disease compared with test and slaughter
      programme: epidemiological and economical evaluations.
AB  - In January 1990, a 6-year program was initiated to eliminate endemic Aujeszky's
      Disease virus (ADV) infection from the pig herds in an area of Northern Germany,
      bordering Southern Denmark, with intensive pig farming. In the first 3 years of
      the campaign, an intensive compulsory vaccination program, with glycoprotein I
      (gI)-deleted vaccines, of all pigs in the area was employed. Beginning in June
      1990 and for the first 3 years of the project, approximately 200 herds randomly
      selected from all herds in the area, were serologically tested each quarter. In
      each farrow-to-feeder (FAFE), feeder-to-finish (FEFI) and farrow-to-finish (FAFI)
      herd, 20 female breeding pigs, 20 finishing pigs (> or = 50 kgs liveweight) and
      10 female breeding pigs and 10 finishing pigs, respectively, were blood sampled.
      The sera were tested by the Herd-Check Anti-PRV(S) ELISA test (IDDEX Inc., ME).
      Sera positive to this test were examined by the HerdCheck Anti-ADV gI-ELISA test
      (IDDEX Inc., ME). Data on potentially confounding management factors were
      collected through a pilot-tested questionnaire, administered to farmers by 2
      veterinarians who blood sampled the pigs. For fattening herds (FEFI and fattening
      sections of FAFI herds), the association between the odds of > or = 1 gI+
      finishing pigs and the time between initiation of the program in the area and
      sampling date (a surrogate for the effect of the program) was modelled using
      ordinary logistic regression. The association between the odds of gI+ females in
      seropositive (> or = gI+ females) FAFE and FAFI herds and time since initiation
      of the program was investigated with logistic-binomial regression models. Results
      of the study show that the longer the period from the beginning of compulsory
      vaccination to the date the herd was sampled the lower the odds of gI+ fattening
      herds and gI+ female breeding pigs in herds of the area. The beneficial effect of
      mass vaccination on the reduction of ADV spread was accounted for by this
      relationship. For fattening herds this relationship appeared curvilinear, with
      the reduction in the log-odds being more rapid in the 1st year of the program.
      This non-linear pattern indicates that for the elimination of the risk of ADV
      infection from fattening herds of the area, the mass vaccination program should
      be complemented with additional measures such as test-and-slaughter of infected
      breeding pigs. A computerized economical model to estimate the effects of ADV
      infection at the herd and area level has been developed. The analytical structure
      consists of a basic epidemiological model linked to an economic estimation
      framework. The economic model predictions allow priorities to be given to
      alternative control strategies. Mass vaccination of all pigs in regions with
      endemically infected herds followed by test-and-removal of seropositive animals
      is the most cost-effective way to control the spread of ADV within the swine
      population. Other possible control strategies such as intensive vaccination or
      complete test-and-removal all had higher overall costs, either because of the
      less efficient production, or because of the high costs of straight test-and
      removal.

PMID- 8996886
TI  - Vaccination against Newcastle disease significance of strain diversity.

PMID- 8996887
TI  - Experiences with different vaccines and vaccination procedures to control
      furunculosis in sea-reared Atlantic salmon.

PMID- 8996888
TI  - Economic evaluation of national eradication and control strategies for Mycoplasma
      hyopneumoniae in Denmark.

PMID- 8996889
TI  - Cost-benefit considerations of vaccination against ringworm in cattle.

PMID- 8996890
TI  - Decision criteria for vaccination against Salmonella in poultry.

PMID- 8996891
TI  - Attitude of the European Community to vaccines.

PMID- 8996892
TI  - Licensing of veterinary vaccines.

PMID- 8996893
TI  - National considerations in the Nordic countries regarding vaccine licensing.

PMID- 8996895
TI  - What to expect of future vaccines?

PMID- 8996894
TI  - Advantages and disadvantages of using live vaccines risks and control measures.

PMID- 8996896
TI  - Arterial complications of pancreatitis and their radiological management.
AB  - Arterial haemorrhage from pseudoaneurysm in pancreatitis patients is a formidable
      complication with a high mortality rate. We encountered six patients in whom a
      pseudoaneurysm was demonstrated at angiography. Drainage of associated pseudocyst
      facilitated visualization in one patient. Four patients had pseudoaneurysms
      arising from the proximal part of the major peripancreatic vessels and were
      treated by steel coil embolization (n = 3) and surgically (n = 1). There was no
      episode of rebleeding in these patients during a follow-up period of 10-18
      months. Of the two patients with distal small peripancreatic branch vessel
      involvement hydrogel particle and gelfoam embolization was successful only
      temporarily in one patient and unsuccessful in the other patient. The literature
      is reviewed and the efficacy of steel coil embolization is emphasized.

PMID- 8996897
TI  - Mammography in men with breast cancer: review of the mammographic findings in
      five cases.
AB  - Male breast carcinoma is an uncommon malignancy. The age at diagnosis and tumour
      stage are more advanced in males than in females. Poor alertness of both men and
      physicians for this infrequent disease may account for the delay in diagnosis. In
      this study, we reviewed male breast carcinomas seen within a 3 year period and
      assessed the mammographic findings. There is limited experience in the diagnosis
      of breast carcinoma in male patients and this has been considerably influenced by
      the knowledge of female breast cancer. The diagnostic criteria for the female
      counterpart cannot always be safely applied to male breast cancer. Mammograms of
      men with breast cancer usually show an uncalcified subareolar mass, which may
      mimic or be obscured by gynaecomastia. Occasionally, punctate calcifications may
      indicate malignant disease in the male breast. Early detection of male breast
      cancer may prolong the survival rate as in cases of female breast cancer.

PMID- 8996898
TI  - Breast MRI: early experience with a 3-D fat-suppressed gradient echo sequence in
      the evaluation of breast lesions.
AB  - The early clinical experience with a 3-Dimensional Fourier Transform Gradient
      Echo sequence with fat suppression in the evaluation of breast masses is
      reported. Ten female patients with breast malignancies were pre-operatively
      evaluated with this sequence and the results compared with the pathological
      specimens. The scanning protocol included a non-contrast sequence followed by an
      immediate post-contrast sequence (completed 4.5 min after intravenous contrast
      injection) and a delayed sequence. Images were assessed for maximum lesion and
      parenchymal enhancement, lesion size and additional enhancing abnormalities. In
      six patients, malignant masses enhanced maximally on the immediate post-contrast
      sequence with parenchyma enhancing maximally on delayed images. In three cases,
      there was preferential enhancement of malignant lesions over normal parenchyma
      but to a similar degree on both post-contrast sequences. In one case, both the
      lesion and parenchyma enhanced maximally on the delayed sequence. Magnetic
      resonance assessed lesion size accurately and also detected satellite
      malignancies in one case. However, lesion grade, associated in situ carcinoma and
      lymphovascular invasion did not impact on lesion enhancement. In this small
      series, a contrast-enhanced, fat-suppressed 3-D Gradient Echo Sequence detected
      breast carcinoma with high sensitivity. The technique holds promise but further
      evaluation is required.

PMID- 8996899
TI  - Paediatric tracheobronchomalacia and its assessment by tracheobronchography.
AB  - Tracheobronchomalacia (TBM) is a rare condition that results in abnormal
      compliance of the airways with airway collapse being most marked in expiration.
      In a series of 28 patients, it was observed that a majority of cases presented
      with malacia involving the trachea (64%) and the left main bronchus (64%) alone.
      The right main bronchus was involved in combination with the trachea in 32%, but
      rarely was involved by itself. Most patients demonstrated associated congenital
      abnormalities, such as tracheo-oesophageal fistulae, vascular rings or congenital
      heart disease (78%). A small proportion were premature infants with no obvious
      associated abnormality (11%). Evaluation of the dynamic process,
      tracheobronchomalacia; requires 'real-time' investigation. While computed
      tomography (CT) and magnetic resonance imaging (MRI) have their role in the
      management of chronic airway obstruction in the child, only cine-CT,
      bronchoscopy, fluoroscopy and tracheobronchography provide real-time assessment
      for the evaluation of a dynamic process such as TBM. In our experience,
      tracheobronchography provides excellent anatomic, physiologic and therapeutic
      information in the assessment of those infants with primary or secondary TBM. By
      using continuous positive airway pressure in incremental doses, the amount of
      positive pressure required to maintain an open airway in expiration is a valuable
      adjunct to the clinical management of the patient. When careful attention is paid
      to technique, tracheobronchography is a safe investigation in experienced hands.

PMID- 8996900
TI  - Migration and lymphatic spread of calcified paraffinomas after breast
      augmentation.
AB  - A 62 year old Chinese woman presented 25 years after having both breasts
      augmented with paraffin injections. Development of paraffinomas and multiple
      episodes of paraffin-related mastitis eventually resulted in bilateral
      mastectomies. The unusual distribution of migrated calcified paraffinomas in the
      thoracic wall and its lymphatic system is documented on computed tomography.

PMID- 8996901
TI  - Assessment of an online radiology reporting system.
AB  - This study was designed to assess the efficiency of radiology reporting in the
      Royal Adelaide Hospital Department of Radiology, which introduced online
      reporting in November 1994. Seventeen radiologists were monitored without their
      knowledge, and recordings were made of the times between report dictation and
      report typing, and the time that the report waited on computer for verification.
      The total median values for verification time for 9/17 radiologists were less
      than 12 h and for 14/17 were less than 24h. On average, reports were available
      from all reporting areas within 24 h. However, some reports waited up to 13 and
      14 days to be verified and to be available on computer for treating clinicians.
      This report demonstrates that on average rapid reporting is occurring, however
      some areas need to be considered further to maximize efficiency.

PMID- 8996902
TI  - Ultrasonography of breast hamartomas.
AB  - The authors present the breast ultrasound findings of nine women with
      mammographic abnormalities typical of breast hamartomas. Two of the
      mammographically detected hamartomas could not be identified at breast
      ultrasound. Six hamartomas were well-circumscribed masses of heterogeneous
      echogenicity with no posterior acoustic shadowing. One lesion was a well-defined
      hypo-echoic mass with no posterior shadowing. We conclude that many
      mammographically and clinically detected hamartomas can be clearly identified at
      breast ultrasound. The breast sonographer should be aware of the spectrum of
      appearances that may occur. When a breast abnormality has the characteristic
      mammographic appearances of a hamartoma, it may be counterproductive to perform
      an additional breast ultrasound.

PMID- 8996903
TI  - Duplex ultrasound in the pre-operative assessment of varicose veins.
AB  - A technique for the pre-operative localization of sites of incompetence using B
      mode and Doppler ultrasound (duplex) is described. The reliability of this
      investigation was compared with the clinical assessment of a group of surgeons
      experienced in varicose vein surgery, and with the subsequent surgical findings.
      Duplex scans were found to be over 98% sensitive and 93-97% specific compared
      with the surgical findings. Clinical techniques were much less sensitive and
      specific, and in addition there was uncertainty about incompetence in up to 52%
      of cases. The place of ultrasound and comparison with other techniques is
      discussed. While this technique is widely used, especially in vascular
      laboratories, the technique has not previously been reported in detail.

PMID- 8996904
TI  - The role of radiation therapy in Graves' ophthalmopathy.
AB  - Graves' ophthalmopathy can occur in 25-30% of patients with hyperthyroidism. This
      condition can result in serious visual disturbance and disfigurement. The
      treatment options for symptomatic disease are oral corticosteroids or orbital
      irradiation. Ten patients with Graves' ophthalmopathy were treated with external
      beam radiotherapy at Saint Lukes Hospital from March 1991 to February 1994. Eight
      of these patients had excellent response with minimal morbidity. We believe that
      orbital radiotherapy is effective and well tolerated, and should replace
      corticosteroid therapy as the initial treatment modality in these patients.

PMID- 8996905
TI  - Concurrent chemoradiation for oesophageal cancer: factors influencing
      myelotoxicity.
AB  - Concurrent chemotherapy and radiation (CT/RT) for localized oesophageal cancer
      can cause life-threatening myelosuppression. This non-randomized study examines
      95 patients from three Australasian centres treated on the Trans-Tasman Radiation
      Oncology "definitive' chemoradiation study. Duration of fluorouracil infusion and
      patient age were independently predictive of myelotoxicity after the first cycle
      of CT/RT. Overall rates of grade III and IV neutropaenia were 23% and of
      thrombocytopaenia 8% following the first cycle of chemotherapy. Five neutropaenic
      septic episodes followed the first cycle and six the second. All five patients
      recovered after the first cycle but there were four treatment-related deaths
      occurring after the second cycle of CT/RT. Recommendations are made concerning
      initial dosing, dose reductions and delays to minimize adverse patient outcomes
      from myelosuppression.

PMID- 8996906
TI  - The role of radiotherapy in thymomas.
AB  - Thymoma is a rare disorder and the treatment of invasive disease is
      controversial. Seventeen patients with pathologically confirmed thymoma were
      treated at Royal Prince Alfred Hospital between 1982 and 1993. There were two
      stage 1 patients, four stage 2 patients and 11 stage 3 patients. Five patients
      had total resection, eight patients had subtotal resection and four patients had
      biopsy only. All patients received radiotherapy, with the median dose being 50
      Gy. The median survival was 117 months and the 5-year survival was 69%. This was
      influenced by stage of disease and extent of surgical resection. The local
      control was 76%. Three patients developed distant metastatic disease. There were
      insufficient numbers to determine a dose response to radiotherapy. Patients with
      invasive disease should continue to have postoperative radiotherapy. A brief
      review of the literature is made.

PMID- 8996907
TI  - Cranial cystic epidermoid: report of two cases and review of the literature.
AB  - Intercranial epidermoid tumours are benign lesions of congenital origin that are
      potentially curable. Although computerized axial tomography (CT) and magnetic
      resonance imaging (MRI) are usually diagnostic, a few atypical features sometimes
      make pre-operative diagnosis difficult. Two cases of cystic epidermoids with
      peripheral ring enhancement are reported. Relevant literature has been reviewed.

PMID- 8996908
TI  - Two cases of chronic recurrent multifocal osteomyelitis: radiological and
      scintigraphic findings.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is an extremely rare condition,
      of uncertain aetiology. Since first described, in 1972, under 100 cases have been
      reported. It is being reported with increasing frequency, and many cases of this
      disease go unreported. It most commonly affects patients in childhood or
      adolescence. No infective agent has been identified, and antibiotics do not
      affect the course of the disease. We present the cases of two female children
      with this disorder, describe the radiological and scintigraphic findings and
      review the literature. Case 1 is the first reported case to our knowledge of CRMO
      presenting with cranial nerve palsies.

PMID- 8996909
TI  - Intramural aortic dissection.
AB  - We present 10 cases of intramural aortic dissection. The cases are all
      characterized by the presence of intramural haematoma without the presence of a
      patent false lumen. The radiological features and possible aetiologies are
      discussed. The key radiological finding is the presence of a hyperdense rim in
      the aortic wall on a non-contrast-enhanced computed tomography (CT) scan. In one
      case, a delayed diagnosis was made using magnetic resonance imaging (MRI). In a
      further case, the delayed development of a large aortic ulcer was demonstrated.
      Intramural aortic dissection has only recently been described in the radiological
      literature. The aetiology of this condition remains controversial. The imaging
      findings may be subtle and the diagnosis is still frequently being overlooked. We
      believe CT to be the primary diagnostic test for this condition, and its
      advantages over MRI and transoesophageal echocardiography (TOE) are discussed.

PMID- 8996910
TI  - Pneumomediastinum: an acute presentation of the superior mesenteric artery
      syndrome.
AB  - The authors report a case of the superior mesenteric artery syndrome presenting
      acutely with a Boerhaave-type syndrome. Pneumomediastinum was seen on the chest X
      ray. There were no known predisposing factors or previous history typical of this
      syndrome.

PMID- 8996911
TI  - Concomitant presentation and resolution of a post-traumatic pneumothorax and
      pneumopericardium.
AB  - The association of a right pneumothorax and a pneumopericardium due to non
      penetrating trauma is exceedingly unusual. A patient with both complications
      presented 7 hours after a motorcycle accident. These were detected incidentally
      on a scout film for CT for lumbar fractures and both resolved entirely and
      simultaneously after chest tube insertion in the right pleural space.

PMID- 8996913
TI  - A review of the radiological features of intracranial meningiomas.
AB  - To evaluate the role of radiological imaging of meningiomas in confirming the
      diagnosis and as a neuroanatomical aid to surgical planning, 115 patients with
      surgically excised meningiomas between 1990 and 1993 were studied. Computed
      tomography (CT), magnetic resonance imaging (MRI) (on a 0.5 T unit) and
      angiography were reviewed, and compared with histopathology (when available).
      Seventy-eight CT, 89 MRI and 85 angiographic studies were reviewed, and
      correlated with histopathology in 67 cases. In 48 cases, the surgical specimens
      could not be pathologically classified. The most common lesion sites were the
      cerebral convexities, falx and sphenoidal ridges. True demarcation of cleavage
      planes was seen on 73% of MRI and 10% of CT studies. Computed tomography showed
      hyperostosis in 27% and MRI in 7% of studies. Tumours enhanced strongly with
      contrast in 98% of CT scans. On MRI there were variable signal intensities on
      different sequences, and no correlation between signal intensities and
      histological subtype was found. Oedema was present in 59% of CT and 66% of MRI
      studies, and was most pronounced in lesions > 3 cm in diameter. Tumour
      calcification was seen in 62% of CT and 8% of MRI studies. Vascular abnormalities
      were seen on 65% of MRI, 21% of CT and 84% of angiogram studies. Angiographic
      tumour vascularity did not correlate with histologic subtype. All three imaging
      modalities have management roles: CT for bony changes and calcification, MRI for
      multiplanar and vessel anatomy imaging, and angiography for vessel delineation
      and embolization if required.

PMID- 8996912
TI  - Synovial sarcoma: an unexpected ultrasound finding in a post-partum patient.
AB  - A 20-year-old patient presented after an uneventful pregnancy and delivery with
      an asymptomatic soft-tissue mass behind her knee with the clinical features of a
      ganglion or Baker's cyst. An ultrasound scan demonstrated a well-defined but
      solid mass with prominent vascularity. The mass was noted to increase in size
      prior to surgery. The pathological diagnosis was that of a synovial sarcoma grade
      2, a rare malignant mesenchymal neoplasm with a serious prognosis.

PMID- 8996915
TI  - Clinical teaching in oncology.

PMID- 8996914
TI  - Case quiz. Lymphographic demonstration of chylothorax.

PMID- 8996917
TI  - Professional debate.

PMID- 8996918
TI  - Mike Grace interviews Keith Marshall.
AB  - Keith Marshall has many achievements to his name, not the least of which is his
      involvement in a semi-professional jazz band. As well as continuing to work part
      time in a wholly private practice in Edenbridge, Kent, he is currently chief
      dental adviser of BUPA DentalCover and chairman of the Dental Advisory Panel.
      Here, Mike Grace gets to know the man behind the dentist.

PMID- 8996919
TI  - A personal, historical view of the management of tooth wear.
AB  - The management of caries, periodontal disease and tooth wear has followed similar
      patterns over the last 30 years but at different rates. The reduced emphasis on
      surgery in the treatment of periodontal disease has now caught up with minimum
      interventive treatment of caries. Tooth wear is still, in my opinion, often over
      treated and it is time that the management of tooth wear followed the same
      pattern.

PMID- 8996920
TI  - General anaesthesia in dentistry.

PMID- 8996921
TI  - Eating disorders.

PMID- 8996922
TI  - Dental attendance patterns.

PMID- 8996923
TI  - Teenage smoking.

PMID- 8996925
TI  - Preparation of guide planes using a reciprocating handpiece.
AB  - A reciprocating handpiece and attachments have been found effective in preparing
      guide planes prior to the construction of removable partial dentures. A
      comparison was made of the enamel surface prepared using the reciprocating
      handpiece and a conventional rotary handpiece. Two-stage and three-stage
      techniques for each handpiece were compared. Scanning electron micrographs showed
      that a smoother surface was created by the reciprocating handpiece.

PMID- 8996924
TI  - Specialist orthodontics in the General Dental Service.
AB  - This study investigated treatment times and treatment standards produced by 10
      specialist orthodontic practitioners working in the General Dental Service (GDS)
      in England. Twenty cases from each practitioner, consecutively completed with two
      arch fixed appliance therapy, were selected and assessed to evaluate treatment
      times and treatment standards. Observer-generated timings were recorded to
      provide values for the time taken by these practitioners to perform the various
      component activities associated with fixed appliance orthodontic therapy. These
      timings were then pooled to produce an 'average' value for each procedure.
      Treatment time was assessed retrospectively by applying these average times to
      the appropriate appointments, as documented on the patient's record card. The
      treatment duration, number of visits, appliance type and extraction regime were
      also recorded. Treatment standards were assessed by applying the weighted Peer
      Assessment Rating Index (PAR Index) to pre- and post-treatment study casts.
      Relationships between each of these variables were investigated using multiple
      regression analysis. No relationship was found between treatment time and PAR
      score change. Predictors of treatment time were the number of visits, and more
      interestingly, the use of extra-oral forces. However, no useful predictors of the
      treatment standard were found. On the basis of this sample, it appears that when
      specialist orthodontic practitioners in the GDS provide two-arch fixed appliance
      therapy: treatment is completed, on average, in 3-5 hours of chairside time, in
      20 visits, spread over 22 months; they provide a high standard of treatment, as
      assessed by the PAR Index, to a caseload of patients in need to treatment.

PMID- 8996926
TI  - DIY dentures--a case report.
AB  - Minor self adjustments to dentures is a common finding. This case report
      describes do-it-yourself major adjustments to a removable prosthesis in an
      attempt to convert it to a fixed prosthesis and the resultant damage to the
      dental tissues.

PMID- 8996927
TI  - Feel free to browse....

PMID- 8996928
TI  - Electronic infrared thermography as a dental research technique.
AB  - Electronic infrared thermography is an imaging modality for the accurate
      quantification of surface temperature. It has been used in medicine since the
      1960s but its use in dentistry has been limited. Its use in dentistry could,
      however, be very useful, for example in objectively quantifying post-surgical
      inflammation and studying the effects of treatment with agents such as analgesics
      and anti-inflammatory drugs.

PMID- 8996929
TI  - Maxillofacial trauma at RAF War Hospital, Wroughton.
AB  - The following article is a historic look at maxillofacial trauma at the Royal Air
      Force War Hospital at Wroughton from D-Day to VE Day. The article describes the
      pattern of injury and the management of personnel injured on the Continent and
      evacuated to Wroughton by air ambulance.

PMID- 8996930
TI  - Remember to test diarrhoeal stools for Escherichia coli O157.

PMID- 8996931
TI  - Shortage of varicella zoster immunoglobulin prompts restriction on use.

PMID- 8996933
TI  - Toxigenicity & drug sensitivity of Vibrio mimicus isolated from patients with
      diarrhoea.
AB  - In a total of 720 faecal specimens from patients with secretory diarrhoea,
      vomiting, dehydration, gastroenteritis, cholera and cholera like illnesses, 18
      strains of V. mimicus were isolated as pure culture. These were characterized for
      various toxin types and virulence factors using conventional in vitro and in vivo
      assays. Labile and stable toxins were elaborated by 15 and 2 strains respectively
      by ligated rabbit ileal loop (RIL) and suckling mouse assays. While 15 of the
      whole cell culture elaborated labile toxin, only 7 strains produced the same when
      culture filtrate was tested in RIL assay. Culture filtrates of 15 strains
      exhibited vascular permeability factor (PF) on adult rabbit skin, none of the
      strains were invasive as indicated by Sereny's test. Culture supernatants of all
      strains produced a cytotoxic factor to Vero and Chinese hamster ovary cells. Four
      of the 18 strains (22%) were resistant to multiple drugs (a combination of 3 or
      more drugs). The results emphasize the significance of continuous screening and
      identification of V. mimicus and to include in the differential diagnosis of
      patients with acute diarrhoea.

PMID- 8996932
TI  - Evidence for high prevalence & rapid transmission of HIV among individuals
      attending STD clinics in Pune, India.
AB  - Prevalence and incidence of HIV-1 infection among persons attending two STD
      clinics in Pune between May 1993 and October 1995 are reported. On screening 5321
      persons, the overall prevalence of HIV-1 infection was found to be 21.2 per cent,
      being higher in females (32.3%) than in males (19.3%). Analysis of behavioural
      and biological factors showed that old age, sex work, lifetime number of sexual
      partners, receptive anal sex, lack of circumcision, genital diseases and lack of
      formal education were related to a higher HIV-1 seroprevalence. The observed
      incidence rate of 10.2 per cent per year was very high, much higher in women than
      in men (14.2% and 9.5% per year respectively) and over three times higher among
      the sex workers. Females in sex work, males having recent contacts with female
      sex workers (FSWs) and living away from the family and persons with previous or
      present genital diseases had a higher risk of seroconversion. Condom usage was
      shown to have a protective effect in seroprevalence and seroincidence analysis.
      With limited available resources and lack of a suitable vaccine or a drug, long
      term prevention policy of creating awareness in the community must be
      supplemented by strengthening STD control measures and promotion of condom use
      and safe sex. Factors related to availability and utilization of condoms must be
      carefully investigated.

PMID- 8996935
TI  - Antigenic differences between axenic amastigotes & promastigotes of Leishmania
      donovani.
AB  - The axenic amastigotes of an Indian strain of L. donovani have been generated
      from the promastigote form at 37 degrees C in RPMI-1640 medium, pH 6.0 +/- 0.5,
      supplemented with 10 per cent heat inactivated foetal calf serum and these are
      being maintained through serial subculturing under the same conditions. The
      present study was carried out to differentiate axenic amastigote from the
      promastigote stage on the basis of their antigenic constitution and also to look
      for any immunoreactive antigen(s) specific to axenic amastigotes. SDS-PAGE
      analysis revealed a few stage specific and some conserved antigenic fractions in
      both the stages. On immunoblotting with immune sera raised against the membrane
      fractions of the axenic amastigotes, the 200 kDa antigenic fraction of axenic
      amastigote was found to be highly reactive. When the immune sera raised against
      the membranes of both stages were checked by immunofluorescence no cross
      reactivity was observed at higher dilutions. These findings showed that there are
      some antigenic diversities as well as similarities between the two stages of L.
      donovani cultured in vitro. Also, the 200 kD fraction of axenic amastigote
      appeared to be an immunodominant antigen specific to that stage.

PMID- 8996934
TI  - A preliminary study of fingerprinting of Pseudomonas aeruginosa by whole cell
      protein analysis by SDS-PAGE.
AB  - Forty two strains of Pseudomonas aeruginosa isolated from bronchoalveolar lavage
      fluid from intubated patients admitted to the Intensive care unit in AIIMS
      between December 1993 to June 1994 were included in the study. After obtaining
      typical biochemical profile, antimicrobial susceptibility was performed against
      ceftazidime, amikacin, gentamicin, ampicillin, cefotaxime and ciprofloxacin.
      Pyocin typing of these 42 strains was performed by scrape and streak method using
      22 indicator strains. Forty strains could be typed showing excellent
      discrimination but on repeated testing the group designation changed indicating
      that the system had low reproducibility. SDS-PAGE of whole cell protein profile
      indicated the presence of 45 protein bands of different molecular weights,
      individual isolates had 37 to 42 protein band ranging in molecular weight from
      340 kDa to 14.3 kDa. On the basis of Dice index of similarity the strains could
      be grouped into 20 types. Since all strains could be typed, the system has
      adequate typability. Similar results were obtained on repeated testing indicating
      good reproducibility.

PMID- 8996936
TI  - Delta F 508 molecular mutation in Indian children with cystic fibrosis.
AB  - A preliminary report of 13 Indian children with cystic fibrosis who were screened
      for the commonest mutation (delta F 508) is presented. Six (46%) patients were
      homozygous for delta F 508, while two patients were compound heterozygotes. Thus
      14 (53.8%) of 26 mutant chromosomes had delta F 508 mutation. These findings
      confirm that cystic fibrosis occurs in India and all children with persistent
      respiratory problems and/or malabsorption should be screened for this disease.

PMID- 8996937
TI  - Bronchial responsiveness of non-smoking women exposed to environmental tobacco
      smoke or biomass fuel combustion.
AB  - We studied bronchial responsiveness (BR) in three groups of housewives with or
      without history of exposure to tobacco smoke or combustion of biomass fuels.
      Methacholine bronchoprovocation test was used to study BR. The group I subjects
      (60), who served as controls, were nonsmokers and had no chronic exposure to
      passive smoking or environmental tobacco smoke (ETS) or biomass fuels. Three of
      these women showed a 20 per cent FEV1 fall with a cumulative methacholine dose of
      72.5 mg or less. Of 60 women in group II (ETS-exposure) and 52 in group III
      (biomass exposure), 26 (43.3%) and 10 (19.2%) respectively showed bronchial hyper
      responsiveness (BHR). The odds ratios for BHR in groups II and III were 14.53 and
      4.52 respectively. The number of hyper-responders was significantly more and the
      mean PD20 less in the exposed than the non-exposed groups. The occurrence of BHR
      in the ETS exposed group was more (P < 0.05) than the biomass combustion group.
      There were more hyper-responders (both groups II and III) amongst those who had
      an exposure index (EI) of 50 or more compared to those with EI of less than 50.
      We conclude that chronic cumulative exposure to both ETS and biomass combustion
      produces significant BHR. Further, BHR developed more often on ETS exposure, and
      when the exposure was present for a longer period.

PMID- 8996938
TI  - Detection of haemoglobin variants for the diagnosis of beta thalassaemia & other
      haemoglobinopathies using anion exchange high performance liquid chromatography.
AB  - We describe the precise identification, separation and quantitation of several
      haemoglobin (Hb) variants such as Hbs A2, A, F, S, E, J, H, D-Punjab and Q-India
      in untransfused patients with beta thalassaemia and other haemoglobinopathies
      prevalent in the Indian population using whole blood (5 microliters), red cell
      lysates (2 microliters) or dried blood specimens on filter paper, using a
      conventional anion exchange high performance liquid chromatography (AX-HPLC)
      system. Samples were simultaneously studied for the presence of haemoglobin
      variants by alkaline electrophoresis. The problems in analysing rare variants and
      separating the closely migrating variants, encountered in the conventional
      methods could be resolved using the HPLC technique.

PMID- 8996939
TI  - A cytological study of hepatitis B surface antigen localization using orcein
      staining in hepatocellular carcinoma.
AB  - Twenty patients of suspected hepatocellular carcinoma (HCC) were studied to test
      the hypothesis that orcein staining of cytological specimens from HCC can detect
      hepatitis B surface antigen (HBsAg). HBsAg status, cytological examination of
      fine needle aspiration cytology (FNAC) material for diagnosis by Papanicolaou and
      modified orcein staining for HBsAg were carried out. Observer variability and
      agreement on orcein positivity was assessed and analyzed using kappa statistics.
      HCC was diagnosed in 13 patients and 8 were HBsAg positive; 8 had orcein
      positivity as judged by observer 2 and 7 by observer 1. A significant kappa value
      of 0.837 suggested a high degree of observer agreement in the interpretation of
      orcein positivity. This technique is safe and quick and can supplement the
      histopathological diagnosis of hepatitis B virus associated HCC.

PMID- 8996940
TI  - Psychosexual morbidity following gynaecological malignancy.

PMID- 8996941
TI  - Management of chronic obstructive pulmonary disease.

PMID- 8996943
TI  - The role of nutrition in liver disease.

PMID- 8996942
TI  - Rheumatoid arthritis: changing concepts of treatment.

PMID- 8996945
TI  - Sudden unexpected death in epilepsy (SUDEP)

PMID- 8996944
TI  - Infectious disease risk in creche, day-care and pre-school.

PMID- 8996946
TI  - Acetylcysteine in paracetamol poisoning--no drug is a safe drug!

PMID- 8996947
TI  - European Consensus Guidelines identify acid pump inhibitor based triple therapy
      as today's treatment of choice for H. pylori eradication.

PMID- 8996948
TI  - Head injuries in the Republic of Ireland: a neurosurgical audit.
AB  - We examined prospectively over a twelve month period, all head injury admissions
      to a National Neurosurgical Unit. Patient characteristics, type and severity of
      injury, distances and time intervals involved in inter-hospital transfers,
      treatment administered and functional outcome, are reported. We illustrate the
      effects of inter-hospital distance travelled on outcome, we urge early
      recognition of potential intracranial injuries and advise rapid transfer of
      stabilised patients to a neurosurgical unit for assessment and management. These
      original data indicate that acute head injuries are a major medical problem in
      this country disabling a young population with unknown socio-economic
      consequences.

PMID- 8996949
TI  - What cost chronic pain?
AB  - Chronic non-malignant pain costs the American economy $40 billion a year. An
      attempt to quantify the total cost to the Irish economy of 95 patients attending
      a Multi-Disciplinary Pain Clinic was made. The cost to the Health Services was
      estimated and added to the amount of Social Welfare payments received and the
      lost earnings of each patient. The results indicated that the 95 patients cost
      1.9 million pounds at the time of referral. A subgroup of 22 patients who were
      younger and unemployed, accounted for 1.5 million pounds. Allocation of resources
      to treat these patients is necessary.

PMID- 8996950
TI  - Do Irish general practitioners know how often their patients consult?
AB  - We report a study of the accuracy with which nine General Practitioners estimated
      the consulting rate of 889 patients over the preceding year. We found that their
      estimates were exact in 34% and that only 13 of 118 high frequency attenders were
      not detected. We conclude that single-handed GPs are aware of patient consulting
      rate, which has been shown to be a marker for unmet medical need.

PMID- 8996951
TI  - Impact of a collaborative immunisation programme in an inner city practice.
AB  - OBJECTIVES: To describe the impact of a collaborative immunisation programme,
      between an inner city practice and the Eastern Health Board (EHB). DESIGN: An
      observational study using a computer database formed from practice and EHB
      records. SETTING: One Dublin inner city practice with three partners located in
      an area with a deprived socio-economic profile. SUBJECTS: All patients in the
      practice aged more than six months and less than five years identified both from
      practice registers and opportunistically during study period. RESULTS: 342
      children, older than six months and less than five years were identified at start
      and 464 (a 36% increase) by end of the programme. Uptake changed for DPT from 30%
      before, to 57% after the programme (p < 0.0005), for DT from 15% to 13%, for Hib
      from 7% to 50% (p < 0.0005) and for MMR (over 15 months) from 53% to 75% (p <
      0.0005). Uptake of the DPT, Hib and MMR was 35% among GMS eligible, 51% among GMS
      ineligible (p < 0.005). CONCLUSION: A collaborative immunisation programme
      significantly improved practice uptake rates. These improved rates still do not
      attain declared national targets. To achieve these targets, radical overhaul of
      the immunisation service is required.

PMID- 8996952
TI  - The development of a comprehensive stroke programme in the acute hospital.
AB  - Stroke is the third leading cause of death and an important cause of hospital
      admissions and long term disability. The incidence of stroke is estimated at 200
      per 100,000 of the population, Dublin has approximately 2,400 new strokes per
      annum. In 1989 a comprehensive stroke programme was introduced in St Vincent's
      Hospital. The aim was to provide patients with a coordinated approach to
      rehabilitation. A study of the programme was conducted in 1993 by detailed chart
      review. 129 patients with a clinical diagnosis of stroke were referred to the
      programme during a 12 month period. 27.13% were under age 65 and 72.87% were over
      65 years, 18% died and 44.2% were discharged home, independently mobile. The
      study findings suggest that the comprehensive stroke programme in St Vincent's
      Hospital represents a feasible model of care in the acute general hospital
      setting.

PMID- 8996953
TI  - Ventilation tubes and cholesteatoma.
AB  - Ventilation tubes (VTs) have been extensively used to treat chronic serous otitis
      media over the last 30 years. However, it is not known if this practice has
      affected the incidence of cholesteatoma. A retrospective study was carried out at
      two Regional ENT Centres in Northern Ireland, examining the clinical notes of all
      patients undergoing major ear surgery between 1965 and 1988. The incidence of
      cholesteatoma per operatively in this period varied from 0.01 to 0.16 per 1,000
      of population per year. The total number of cholesteatomas in the first five
      years of the study was exactly equal to the number in the last five years,
      despite an eight-fold increase in VT insertion over this period. These results
      indicate that the incidence of cholesteatoma remained stable between 1965 and
      1988 despite a huge increase in the use of VTs.

PMID- 8996954
TI  - 149 consecutive thyroid operations--indications, technique and outcome.
AB  - One hundred and forty nine patients underwent thyroid and parathyroid surgery
      over a nine year period. The most common indications for surgery were the
      presence of a solitary thyroid nodule (56%) or the onset of pressure symptoms
      (30%). Carcinoma was found in 7.4% of cases. Wound complications occurred in 5%.
      The permanent nerve injury rate was 0.67%. The incidence of permanent
      hypothyroidism after surgery was 4%. No patients developed permanent
      hypoparathyroidism.

PMID- 8996955
TI  - A one-year prospective audit of an asthma education programme in an out-patient
      setting.
AB  - A prospective randomised trial was performed to evaluate the effectiveness of an
      asthma education programme administered by an asthma nurse specialist in an out
      patient setting. Sixty asthmatic patients (mean age 28.5 years) were enrolled, 30
      to a usual care control group and 30 to an education group. The education group
      underwent an individual education programme lasting at least one hour. The
      following variables were measured at baseline, one month after the education
      programme and at one year follow-up: asthma knowledge by MCQ (36 point
      questionnaire), inhaler technique (7 point scale), peak expiratory flow rate
      (PEFR) and symptomatology by visual analogue score (0 to 10 score). The education
      group's inhaler technique and MCQ score both improved significantly at one month,
      from 5.4 (0.3) (mean [SEM]) to 6.5 (0.3), p < 0.001, and from 7.5 (2.4) to 22
      (1.8), p < 0.0001 respectively. Both of these improvements were significantly
      greater than in the control group, and both were maintained at one year follow
      up. The symptom score improved over one year in the education group, from 5.4
      (0.6) to 7.6 (0.5), p < 0.05, and was unchanged in the control group. There was
      no change in the PEFR in either group. This study shows clear objective benefits
      to an out-patient asthma education programme conducted by an asthma nurse
      specialist.

PMID- 8996956
TI  - Fulminant septicaemia.

PMID- 8996957
TI  - Eczema and hay fever in schoolchildren.
AB  - In a questionnaire survey of 2,813 children aged 4 to 19 years, eczema prevalence
      was 7.8% but rose to 21.3% in those with asthma. The prevalence was 5.9% in non
      asthmatics. The hay fever prevalence was 12.3% but rose to 36% in those with
      asthma. The prevalence was 8.9% in non-asthmatics. Hay fever was more common in
      urban than rural children, but there was no town/country difference for eczema.

PMID- 8996959
TI  - Escaped faecalith causing a persistent psoas abscess.
AB  - Faecaliths have been widely implicated in the aetiology of acute appendicitis.
      According to Shaw, stones are formed in the appendix with greater frequency than
      in either the gall bladder or the urinary tract. In spite of this, faecaliths
      appear to cause few complications outside the appendix. We report an unusual
      complication resulting from an escaped appendiceal faecalith.

PMID- 8996961
TI  - Fetal anomaly in twin pregnancies--a cluster!

PMID- 8996958
TI  - The significance of basal systolic murmurs in the elderly.
AB  - Aortic stenosis is common in the elderly. Basal systolic murmurs are also common.
      We studied 512 patients over the age of 65 years to ascertain the prevalence of
      basal systolic murmurs and by using echocardiography on those with basal murmurs
      to determine the prevalence of significant aortic stenosis. 29% (148) of patients
      had basal systolic murmurs. 81 (55%) patients of this group had echocardiography
      carried out and 21 (25.9%) had a gradient across the aortic valve of 30 mmHg or
      more.

PMID- 8996960
TI  - Bioethics body needed.

PMID- 8996962
TI  - Joseph Anton Bruckner (1824-1896)--composer.

PMID- 8996963
TI  - Unstable expansion of triplet repeats as a new disease mechanism for
      neurodegenerative diseases.

PMID- 8996964
TI  - Estimation of the physical distance between major genomic markers in the Werner
      syndrome locus (8p11.2-12) by dual-color fish analysis.
AB  - The gene responsible for Werner syndrome (WS) is considered to be located between
      D8S131 and D8S87 in the 8p11.2-12 region that includes the closest marker D8S339
      (Goto et al. (1992) Nature 355: 735-738). In this experiment, the order of major
      markers in this region was determined and the physical distances between them
      were estimated by dual-color fluorescence in situ hybridization (FISH) using P1,
      PAC and cosmid clone DNAs as probes. The fine overall order of telomere-D8S131
      D8S339-GSR-PP2A beta-D8S283-D8S87-centromere was determined for the first time.
      The distance from D8S131 to D8S87 was estimated to be 1,634 kb. To our surprise,
      the distance between D8S131 and D8S87 is much shorter than previously estimated
      by recombination analysis, 8.3 cM equivalent to 8.3 Mb in physical distance.
      These information provide the basis for the positional cloning of WS gene and the
      identification of its mutation.

PMID- 8996966
TI  - Molecular characterization of an unusual variant of the short arm of chromosome
      15 by FISH-technique.
AB  - One of the most frequent translocations involving the long arm of chromosome Y
      with autosomes is with the short arm of chromosome 15. The regions which are
      involved in this translocation fluoresce brightly, are highly heteromorphic and
      thus escape detection. Therefore, these abnormalities could not be fully
      characterized, especially in cases where parents are not available or paternity
      is disputed. Results from the employment of the selective staining techniques
      DA/DAPI and Q-banding have been inconclusive. FISH-technique using whole
      chromosome painting (WCP) probes should be used to decipher such translocations.
      We present a case where, even after using a battery of probes, the origin of
      extra material on chromosome 15p could not be identified though it was not a part
      of Yq.

PMID- 8996965
TI  - Mutations of the tyrosinase gene in three Korean patients with type I
      oculocutaneous albinism.
AB  - Oculocutaneous albinism (OCA) is an inherited disorder of the melanin pigmentary
      system, characterized by a decrease or an absence of melanin in the skin, hair,
      and eyes. Type I (tyrosinase-deficient) OCA results from mutations of the
      tyrosinase (TYR) gene encoding tyrosinase, the enzyme that catalyzes at least the
      first two steps of melanin biosynthesis. We have analyzed the TYR gene in three
      Korean patients with severe type I OCA. Two patients were compound heterozygotes
      for the Arg (CGG) to Gln (CAG) mutation at position 77 and a C insertion mutation
      at position 310. The other was a compound heterozygote for a C insertion mutation
      at position 310 and the Asp (GAT) to Asn (AAT) mutation at position 383. These
      mutations were easily detected by restriction enzyme digestion or by SSCP
      analysis. Such methods of mutation analysis thus provide a basis for a screening
      system for the TYR gene mutations in Korean patients with type I OCA.

PMID- 8996967
TI  - Two novel mutations in the alpha-galactosidase gene in Japanese classical
      hemizygotes with Fabry disease.
AB  - Four alpha-galactosidase gene mutations were identified in Japanese male patients
      with Fabry disease who had no detectable alpha-galactosidase activity. Two of
      them were novel mutations, an 11-bp deletion in exon 2 and a g-1 to t
      substitution at the 3' end of the splice acceptor site in intron 1. The former
      caused a frameshift and led to the creation of a new stop codon at codon 118. The
      latter was predicted to provoke aberrant mRNA splicing followed by accelerated
      degradation of the mRNA. A nonsense mutation, R301X, and a 2-bp deletion starting
      at nucleotide position 718, which were reported previously, were also identified
      in unrelated patients.

PMID- 8996968
TI  - Small interstitial deletion of the long arm of chromosome 2 (2q24.3): further
      delineation of 2q medial monosomy syndrome.
AB  - We report on a female infant with an interstitial deletion involving 2q24.3. She
      had multiple congenital anomalies similar to those in patients with
      del(2)(q31q33) except for an occipital encephalocele. As a result of comparison
      of clinical findings among interstitial 2q deletions, a distinct 2q medial
      monosomy syndrome may be delineable in association with a deletion of 2q31.

PMID- 8996969
TI  - A Japanese patient with X-linked alpha-thalassemia/mental retardation syndrome:
      an additional case report.
AB  - X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) is characterized
      by severe mental retardation, wide range of minor abnormalities, and association
      with an unusual form of alpha-thalassemia. Fifty patients in Caucasian origin
      have been reported. This is the second report of the syndrome demonstrated in
      Oriental patients.

PMID- 8996970
TI  - Interstitial deletion of the short arm of chromosome 10: report of a case and
      review of the literature.
AB  - The fifth patient with an interstitial deletion of the short arm of chromosome 10
      is described. She showed most of the features observed in other known patients at
      age 20, including psychomotor retardation, distinct facial dysmorphism,
      abnormally shaped skull and cardiac malformation, while she did not show any
      growth retardation. The elevation of serum IgG level was observed from age 15,
      but she did not show DiGeorge syndrome. These differences would be explained by
      the differences in the amount of deleted segments using high resolution
      chromosome banding and molecular methods.

PMID- 8996971
TI  - A recurrent 1992delCT mutation of the type X collagen gene in a Japanese patient
      with Schmid metaphyseal chondrodysplasia.
AB  - We report here a recurrent frameshift mutation within the carboxyl-terminal
      noncollagenous domain coding region of the type X collagen gene (COL10A1) in a
      Japanese patient with Schmid metaphyseal chondrodysplasia. The mutation involves
      deletion of a CT dinucleotide from position 1992 (1992delCT), and produces a
      frameshift which creates a premature termination codon close to the site of the
      deletion. The predicted length of the mutant polypeptide is 664 amino acids,
      which is shorter than the wild type polypeptide (680 amino acids). A 1992delCT
      mutation of COL10A1 has been previously reported in one family. The independent
      occurrence of de novo mutation of this specific dinucleotide repeat suggests that
      this region is a possible mutational hot spot on COL10A1.

PMID- 8996972
TI  - Skin and bone tumors induced by repeated beta-irradiation of mice: threshold
      effect and p53 mutations.

PMID- 8996973
TI  - Protein biosynthesis in low dose ionizing radiation-adapted human melanoma cells.
AB  - Adaptive responses induced by low dose gamma-ray irradiation in human melanoma
      cells were examined using a clonogenic assay. Survival fractions were
      significantly increased in cells irradiated with low dose gamma-rays then 4 hrs
      later with high dose gamma-ray as compared to cells irradiated only with high
      dose gamma-rays. When low dose irradiation was given 20 hrs prior to high dose
      irradiation, however, no adaptive response was induced. Changes in protein
      biosynthesis in human melanoma cells were observed under the same conditions.
      Significant changes in protein biosynthesis occurred in the nuclear and membrane
      proteins of cells first irradiated with a low dose then a high dose of gamma-rays
      after 4 hrs. No such changes were found in cells irradiated with low dose gamma
      rays 20 hrs prior to high dose irradiation, consistent with the results of the
      clonogenic assay. Our findings suggest that prior treatment with low dose gamma
      rays induces an adaptive response that has a significant effect on the induction
      of the nuclear and membrane protein biosynthesis caused by high dose gamma-ray
      irradiation of human melanoma cells.

PMID- 8996974
TI  - Induction of repair capacity for oxidatively damaged DNA as a component of
      peroxide stress response in Escherichia coli.
AB  - We examined whether or not peroxide stress induces a repair capacity for
      oxidatively damaged DNA in Escherichia coli cells. Peroxide stress was brought
      about by adding 30 microM hydrogen peroxide (H2O2) to exponentially growing
      cells. The following results were obtained. (1) After exposure to H2O2, E. coli
      resistance to X-rays was enhanced. The acquisition of resistance was inhibited by
      rifampicin and chloramphenicol. (2) The response was acquired in mutants
      defective in the katG and oxyR genes, as well as in the wild-type strain. (3)
      Lambda phages damaged by exposure to H2O2 showed higher survival on H2O2-treated
      cells than on untreated cells. (4) The peroxide stress did not render E. coli
      cells resistant to UV and mitomycin C. These suggest that peroxide stress induces
      a repair capacity against oxidative DNA damage and that this response must be
      regulated by a different mechanism from oxyR(+)-mediated regulatory system.

PMID- 8996975
TI  - Decrease of erythropoiesis in the fetal liver of X-ray irradiated pregnant mice.
AB  - To accumulate fundamental knowledge about a possible relationship between severe
      mental retardation caused by in utero radiation exposure and impaired oxygen
      transport to fetal brain, the effect of X-ray irradiation on erythropoietic
      activity in fetal liver of C57BL/6J mice was studied in vivo and in vitro by
      measuring 59Fe uptake into heme and nonheme fractions of fetal liver. For the in
      vitro experiments, the mice were irradiated with X-rays at a dose of 189 cGy on
      day 9, 11, 13 or 15 of gestation. The day after irradiation, fetal livers were
      dissected, homogenated, and incubated with 59Fe-labeled mouse plasma. 59Fe uptake
      into the heme fraction of fetal liver was markedly reduced, depending both on the
      fetal developmental stage at the time of irradiation and the time that had
      elapsed since irradiation. In the in vivo experiments, pregnant mice were
      irradiated with X-rays at doses of 24 to 284 cGy on day 15 of gestation. The
      ratios of the amounts of 59Fe incorporated in the heme and nonheme fractions
      significantly decreased when mice were irradiated with more than 1 Gy. These
      results suggested that the necessary amount of oxygen may not be transferred to
      the fetal brain at the time required. The possible relationship between decreased
      fetal liver erythropoiesis and severe mental retardation is described.

PMID- 8996976
TI  - Exposure to magnetic field (5 mT at 60 Hz) does not affect cell growth and c-myc
      gene expression.
AB  - We designed and manufactured equipment for long-term and low-density (0 to 9 mT)
      exposures of cultured cells to extremely low frequency magnetic fields (ELF-MF),
      and examined the effects of ELF-MF on cell growth and c-myc mRNA expression in
      Chinese hamster ovary (CHO) cells. The ELF-MF equipment consists of a CO2
      incubator with a built-in magnet generator using Helmholtz coils being 250 mm in
      inner diameter, 160 mm in distance and 128 turns, a slide regulator and a
      thermocontroller. No significant difference in the growth rate and the c-myc
      expression of CHO cells was observed with 5 mT ELF-MF exposure, sham-exposure and
      incubation in a conventional incubator.

PMID- 8996977
TI  - Cellular effect of thermal neutron capture treatment using 10B1-para
      boronophenylalanine: lethal effect on melanoma cells with different degrees of X
      ray sensitivity.
AB  - We studied the effect of neutron capture treatment using 10B-compound on X-ray
      sensitive P-39 and X-ray resistant G-361 human melanoma cell lines, and found a
      high lethal effect of boron neutron capture therapy in comparison with
      conventional ionizing radiation. The P-39 line was sensitive to thermal neutron
      radiation, and extremely sensitive to bleomycin treatment, whereas the G-361 line
      was resistant to both forms of treatment; however, the two cell lines had similar
      sensitivity to thermal neutron radiation after pretreatment with 10B1-para
      boronophenylalanine (10B1-BPA, 200 micrograms/ml medium). These results show that
      the thermal neutron capture products (a 7Li nucleus and alpha particle) are
      highly damaging and short range in tumor cells and thus more efficiently
      inactivate melanoma cells irrespective of x-ray sensitivity, than conventional X
      ray-irradiation.

PMID- 8996978
TI  - Damage induced by hydroxyl radicals generated in the hydration layer of gamma
      irradiated frozen aqueous solution of DNA.
AB  - Aqueous DNA solutions with or without the spin trap alpha-phenyl-N-tert
      butylnitrone (PBN) were exposed to gamma-rays at 77 K. After thawing the
      solutions, three experiments were carried out to confirm the generation of OH
      radicals in the hydration layer of DNA and to examine whether they act as an
      inducer of DNA strand breaks and base alterations. Observation with the ESR-spin
      trapping method showed ESR signals from PBN-OH adducts in the solution containing
      PBN and DNA, but there were few signals in the solution containing PBN alone,
      suggesting that reactive OH radicals were produced in the hydration layer of
      gamma-irradiated DNA and were effectively scavenged by PBN, and that unreactive
      OH radicals were produced in the free water layer of gamma-irradiated DNA.
      Agarose gel electrophoresis of DNA proved that PBN had no effect on the formation
      of strand breaks, whereas examination with the high-performance liquid
      chromatography-electrochemical detection (HPLC-ECD) method showed that PBN
      suppressed the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). From
      these results it was concluded that OH radicals generated in the hydration layer
      of gamma-irradiated DNA did not induce DNA strand breaks but induced base
      alterations.

PMID- 8996979
TI  - Indomethacin attenuation of radiation-induced hyperthermia does not modify
      radiation-induced motor hypoactivity.
AB  - Exposure of rats to 5-10 Gy of ionizing radiation produces hyperthermia and
      reduces motor activity. Previous studies suggested that radiation-induced
      hyperthermia results from a relatively direct action on the brain and is mediated
      by prostaglandins. To test the hypothesis that hypoactivity may be, in part, a
      thermoregulatory response to this elevation in body temperature, adult male rats
      were given indomethacin (0.0, 0.5, 1.0, and 3.0 mg/kg, intraperitoneally), a
      blocker of prostaglandin synthesis, and were either irradiated (LINAC 18.6 MeV
      (nominal) high-energy electrons, 10 Gy at 10 Gy/min, 2.8 microseconds pulses at 2
      Hz) or sham-irradiated. The locomotor activity of all rats was then measured for
      30 min in a photocell monitor for distance traveled and number of vertical
      movements. Rectal temperatures of irradiated rats administered vehicle only were
      elevated by 0.9 +/- 0.2 degree C at the beginning and the end of the activity
      session. Although indomethacin, at the two higher doses tested, attenuated the
      hyperthermia in irradiated rats by 52-75%, it did not attenuate radiation-induced
      reductions in motor activity. These results indicate that motor hypoactivity
      after exposure to 10 Gy of high-energy electrons is not due to elevated body
      temperature or to the increased synthesis of prostaglandins.

PMID- 8996980
TI  - Induction of a germline mutation at a hypervariable mouse minisatellite locus by
      252Cf radiation.
AB  - Male C3H/HeN mice were exposed to 252Cf radiation and mated with unirradiated
      C57BL/6N females. F1 mice were analyzed for germline mutation at the paternally
      derived C3H/HeN allele of a hypervariable minisatellite locus, Ms6hm. This locus
      exhibited a high frequency of length change mutation spontaneously, and the
      mutation frequency of the paternally derived C3H/He allele in F1 mice born to
      unirradiated males was 8.4%. Exposure of male mice to 252Cf radiation resulted in
      even higher frequency of germline mutation. The spermatid stage germ cells were
      most sensitive to neutrons, and the mutation frequencies of the paternal allele
      were elevated to 18%, 26% and 24% for 0.35, 0.7 and 1.02 Gy of 252Cf radiation,
      respectively. Spermatozoa and spermatogonia stages were less sensitive and the
      mutation frequencies for 1.02 Gy of 252Cf radiation were 16% and 19%,
      respectively. The 252Cf radiation consisted of 35% gamma-rays and 65% neutrons.
      Assuming that these two radiations act additively, RBE of 252Cf neutrons for the
      induction of minisatellite mutation was calculated to be 5.9 for spermatozoa
      stage irradiation, 2.6 for spermatid stage irradiation and 6.5 for spermatogonia
      irradiation.

PMID- 8996981
TI  - Factors associated with congenital malformations in Thailand.

PMID- 8996982
TI  - Serum zinc and copper in healthy adults living in Bangkok and surrounding
      districts.
AB  - Serum zinc and copper concentrations were evaluated in 312 healthy adults aged 20
      80 years, living in Bangkok and surrounding districts, Thailand. Serum zinc and
      copper levels were related to a range of factors such as sex, age, body mass
      index (BMI), blood pressure, drinking and smoking habits. Serum zinc and copper
      concentrations in this population were 12.7 +/- 2.3 (mean +/- S.D.) and 18.0 +/-
      2.8 mumol/L. Mean serum zinc concentrations in males and females were 12.7 +/-
      2.2 and 12.7 +/- 2.3 mumol/L, whereas, mean serum copper was 17.0 +/- 2.8 and
      18.6 +/- 2.7 mumol/L, respectively. Serum copper concentrations in women were
      significantly higher than in men (p < 0.001) while there were significant
      differences in serum zinc and copper levels with age. Serum copper was found to
      be elevated in hypertensives. In general, the results of this study agree with
      previously reported values from different countries.

PMID- 8996983
TI  - Bioequivalence of a generic preparation of oral zidovudine in healthy Thai
      volunteers.

PMID- 8996984
TI  - Effect of TSH-suppressive doses of levothyroxine on bone mineral density in Thai
      women.
AB  - Thyroid hormone stimulates both osteoblast and osteoclast. However, the effect on
      osteoclast exceeds that of osteoblast resulting in a decrease in bone mass. TSH
      suppressive doses of levothyroxine (L-T4) with otherwise normal thyroid function,
      so-called subclinical hyperthyroidism, has been reported to cause a reduction in
      bone mass. However, the sites of bone loss vary among studies. Moreover, the
      effect of menopausal status on thyroid-hormone-induced bone loss is inconclusive.
      Ethnic and geographical differences may modify the skeletal response to thyroid
      hormone. In the present study, we looked at the effect of TSH-suppressive doses
      of L-T4 on bone mineral density (BMD) in Thai pre- and post-menopausal women.
      Subjects consisted of 27 Thai females aged between 23-79 years. Eighteen were
      premenopausal and nine were postmenopausal. All were attending the Thyroid Clinic
      at Ramathibodi Hospital and had been on at least 150 micrograms/day of L-T4 for
      the treatment of nodular thyroid diseases for more than 2 years with at least one
      TSH value during the follow-up period in the suppressive range. None of the
      subjects had a previous history of Graves' disease. BMD was determined by dual
      energy X-ray absorptiometry. Data of 54 age-matched healthy controls were used
      for comparison. BMD values were converted to Z-scores before analyses. Data were
      expressed as mean +/- SEM. Compared to controls, postmenopausal women on long
      term L-T4 had decreased BMD at anteroposterior spine (-0.69 +/- 0.20 vs 0.05 +/-
      0.17, P < 0.01), femoral neck (-0.61 +/- 0.35 vs 0.18 +/- 0.24, P < 0.05),
      femoral trochanter (-0.64 +/- 0.37 vs 0.13 +/- 0.22, P < 0.05) but not at Ward's
      triangle. In contrast to the findings in postmenopausal women. there was no
      significant difference of BMD compared to controls in premenopausal women at the
      lumbar spine, Ward's femoral neck or femoral trochanter. We conclude that Thai
      postmenopausal women on long-term TSH-suppressive doses of L-T4 have reduced BMD
      at various skeletal sites which may increase fracture risks. TSH-suppressive
      doses of thyroid hormone should only be prescribed when appropriate and no longer
      than necessary to minimize this adverse effect of excessive doses of thyroid
      hormone on bone.

PMID- 8996985
TI  - Low dose cytosine arabinoside in the treatment of acute non-lymphoblastic
      leukemia.
AB  - Low-dose ARA-C (10 mg/m2 subcutaneous injection twice/day for 20 days with 10
      days rest) was prescribed in 8 cases of newly diagnosed ANLL. Only one case
      attained complete remission in 2 courses and lasted for one and a half years
      without maintenance therapy. She was 63 years of age. The drug could be tolerated
      well and no serious side effect was observed.

PMID- 8996986
TI  - Video-assisted thoracoscopic surgery (VATS): preliminary experience in Ratchaburi
      Hospital.
AB  - Thoracoscopy is used as an adjunct to traditional diagnostic thoracoscopy.
      Because of advances in endoscopic surgical equipment and anesthetic technology,
      surgical treatment via thoracoscopic is now possible. Between June and November
      1995, seven male and two female patients underwent thoracoscopic procedures under
      general anesthesia with a double-lumen endotracheal tube in Ratchaburi Hospital.
      The procedures for diagnostic purposes included 2 diffuse lung diseases, 1
      pleural metastatic disease; and the procedures for therapeutic purposes included
      1 case of massive pleural effusion, 2 of clot haemothorax, 2 empyema thoracis,
      and 1 solitary pulmonary nodule. The thoracoscopic procedures included 2 lung
      biopsies, 1 pleural biopsy, 2 decortication with removal of blood clots and 2
      decortication of empyema, and 1 pulmonary wedge resection. There was no mortality
      associated with VATS. We believe that the patients have benefited from VATS in
      reducing post-operative pain, rapid recovery, and decreased scarring of the chest
      wall. VATS is a minimally invasive surgical technique causing a low morbidity
      rate and attaining a high diagnostic accuracy.

PMID- 8996987
TI  - Pharmacokinetics of samarium-153-EDTMP in disseminated skeletal metastases.

PMID- 8996988
TI  - Oral antimicrobials in compound fracture of the hand: comparison of dicloxacillin
      and ofloxacin.

PMID- 8996989
TI  - Female sterilization in Ramathibodi Hospital: 1987-1993.
AB  - A 7 year (1987-1993) restropective review of female sterilization in the
      Department of Obstetrics and Gynecology, Ramathibodi Hospital was reported. This
      paper is part of a continuing study of female sterilization in Ramathibodi
      Hospital. A total of 9,968 cases of female sterilization was done from January
      1987 to December 1993. Post partum acceptors accounted for 63 per cent of total
      female sterilization, the overall postpartum female sterilization rate was 117.4
      per 1,000 deliveries. 37 per cent was interval sterilization. The peak of
      interval sterilization was in March. 69.8 per cent of interval sterilization was
      performed by minilaparotomy technique, the remainder were by laparoscopy.

PMID- 8996990
TI  - Evaluation of left ventricular ejection fraction from 99m Tc sestamibi gated
      SPECT.

PMID- 8996991
TI  - Multidrug-resistant tuberculosis: response to treatment.
AB  - OBJECTIVE: We investigated clinical response and mortality rates in 18 HIV-
      negative patients with multidrug-resistant tuberculosis. METHOD: We obtained
      detailed data from our hospital on patients with multidrug - resistant
      tuberculosis defined as tuberculosis resistant at least to isoniazid and
      rifampicin. Therapeutic responses were evaluated by both microbiologic and
      clinical data. RESULTS: From January 1985 to December 1990, 18 HIV-negative
      patients were identified and treated. One patient committed suicide 1 week after
      receiving antituberculous drugs. Of the 17 patients, 10 (58.8%) had clinical
      response as well as microbiologic response, 6 (35.3%) were persisters during 24
      months of follow-up, and 1 (5.8%) died after 30 months of treatment. The median
      follow-up for the patients was 87 weeks (range, 24 to 212). For those who
      responded well, there was no relapse.

PMID- 8996992
TI  - The myeloprotective effect of high dose medroxyprogesterone acetate (HD-MPA) in
      patients with carcinoma of the uterine cervix (stage II & III) treated by
      radiation.

PMID- 8996993
TI  - Replantation of the avulsion of the scalp: a case report.
AB  - We reported a case of successful replantation of the avulsion scalp after 11
      hours of ischemic time. The surgical management and postoperative management were
      presented. The fourteenth month follow-up result was satisfactory.

PMID- 8996994
TI  - The influence of number of embryos transferred on pregnancy outcome in women
      undergoing in vitro fertilization and embryo transfer (IVF-ET).
AB  - The purpose of this study was to retrospectively examine the influence of number
      of embryos transferred on pregnancy outcome in women undergoing in vitro
      fertilization and embryo transfer (IVF-ET) between July 1990-December 1991 at the
      Royal Free Hospital, London, United Kingdom. This study included three groups of
      patients: group 1-the number of embryo used for transferring was one embryo,
      group 2-the number of embryos used for transferring was two embryos and group 3
      the number of embryos used for transferring was three embryos. This study
      demonstrated that the clinical pregnancy rate increased significantly when
      transferring two or three embryos compared to one. But this rate did not differ
      significantly when two embryos were compared with three embryos. The multiple
      pregnancy rate, miscarriage rate, and ectopic pregnancy rate did not differ
      significantly among the three groups studied but there was a risk of higher order
      multiple pregnancy if more embryos were transferred. In this study we found 3
      triplets out of 35 pregnancies when 3 embryos were transferred (Group 3). In
      conclusion, this study demonstrates that when two or three embryos were
      transferred the clinical pregnancy rate increased significantly. Transferring two
      embryos instead of three did not alter the pregnancy rate. Moreover, triplets
      pregnancies were eliminated. Therefore, we suggest limiting the number of embryos
      to be transferred at two and the supernumerary embryos should be cryopreserved
      for future transfer.

PMID- 8996995
TI  - Propofol anesthesia for transvaginal ultrasound guided oocyte retrieval.
AB  - The purposes of this study were to determine the efficacy of propofol anesthesia
      for oocyte retrieval and its effect on IVF outcomes. The anesthetic records of
      339 oocyte retrieval cycles were analysed. The mean of total amount of propofol,
      duration of anesthesia and oocyte pick up were 197.7 +/- 84.2 mg, 25.2 +/- 8.5
      and 19.5 +/- 7.4 minutes, respectively. In all cases propofol induced anesthesia
      within seconds. Mean recovery time was 32.2 +/- 5.4 minutes. Significant nausea
      and vomiting occurred in one patient. Mild hypotension was observed in 55 out of
      339 cycles (16.2%) which did not correlate to the amount and duration of propofol
      used. A total of 3,417 oocytes were obtained. Fertilization occurred in 2,431
      oocytes (71.1%). Mean cleavage rate was 84.5 per cent of fertilized eggs. Mean
      number of transferred embryo was 4.4 +/- 2.0. Embryos were transferred in 321
      cycles, resulted in 73 pregnancies (21.5% per oocyte pick up and 22.7% per
      transfer). Neither the dose of propofol or the duration of anesthesia has
      significant effect on pregnancy rate. Propofol anesthesia was found to be
      efficacious for oocyte retrieval with a rapid induction and recovery, and minimal
      side effects. The fertilization and pregnancy rates are comparable to other
      reports using different anesthetic or analgesic agents. However, to reliably
      determine if propofol affects the IVF outcome a prospective and randomized trial
      should be performed.

PMID- 8996996
TI  - Suppression of spermatogenesis by testosterone enanthate in Thai men.
AB  - To investigate the effect of testosterone enanthate on suppression of
      spermatogenesis in Thai men, 17 normal Thai men were given 200 mg testosterone
      enanthate weekly by intramuscular injection. During treatment, semen was
      collected regularly to monitor spermatogenesis. Median times for the first semen
      sample reaching sperm concentration threshold of 5, 3, 1 and 0 million/ml were
      58, 70, 84, and 85, respectively. Subsequently, all men became azoospermic. Among
      17 men entering the efficacy phase, 14 (82.3%) achieved consistent azoospermic
      from the beginning of efficacy phase, the remaining 3 (17.7%) were initially
      severe oligozoospermic but later became azoospermic. Only one case achieved
      consistent oligozoospermia but did not achieve azoospermia within 6 months. After
      stopping injection, sperm first reappeared in the ejaculate of formerly
      azoospermia men at 73 days. Recovery of sperm output to normal sperm
      concentration (> 20 million/ml) was achieved by all men at a median time of 3.9
      months and recovery to their own baseline in one year after the last injection
      was established in 13/17 (76.5%) at a median time of 4.9 months, respectively. In
      conclusion, testosterone enanthate alone is effective in suppression of
      spermatogenesis for male hormonal contraception due to the high rate of
      azoospermia induced, which is known to ensure reliable and effective, reversible
      contraception.

PMID- 8996997
TI  - Congenital coronary artery fistula: a report of 24 patients.
AB  - Clinical, hemodynamic and angiographic findings of 24 adolescent or adult
      patients with coronary artery fistula were retrospectively analyzed. There were 7
      males and 17 females with the average age of 41.4 years. Nineteen of 24 patients
      (79.2%) were symptomatic and 18 were older than 20 years of age. Continuous
      murmur was present in 17 patients, "to and fro' murmur was audible in 2, apical
      systolic murmur was audible in 1. The remaining 4 patients had no audible murmur.
      Location of murmur in all patients was unusual for patent ductus arteriosus.
      Cardiomegaly on chest X-ray was found in 17 patients (70.8%) in whom 8 had
      prominent pulmonary artery. Electrocardiographic abnormalities were detected in
      10 of 24 patients (41.6%) i.e. left ventricular hypertrophy (4 patients)
      biventricular hypertrophy (2 patients), incomplete right bundle branch block (2
      patients), and ischemic changes (2 patients). The intracardiac pressures were
      slightly elevated and the mean Qp/Qs ratio was only 1.4 +/- 1.2.
      Angiographically, 28 fistulas were demonstrated in 24 patients. The origins of
      fistula were from right coronary artery in 12 patients (50%), left coronary
      artery in 8 patients (33.3%) and both coronary arteries in 4 patients (16.7%).
      Fistulas drained into the right atrium in 5 patients (20.8%), into coronary sinus
      in 2 patients (8.3%), into right ventricle in 4 patients (16.7%), into pulmonary
      arteries in 10 patients (41.7%) and into left ventricle in 3 patients (12.5%).

PMID- 8996998
TI  - Relapse of leprosy after multidrug therapy.
AB  - Relapse of leprosy after multidrug therapy among leprosy patients treated at
      Mahasarakarm, Kalasin and Roi-et from 1984 to 1994 were analyzed. Twenty PB
      relapses (45.45%) and twenty four MB relapses (54.55%) were found among 5,298
      originally classified PB patients and 5 MB relapses occurred in 2,624 originally
      classified MB patients. Mean relapse interval was between 3-4 years. The relapse
      rate within 10 years after stopping MDT was 0.83 per cent in PB and 0.19 per cent
      in MB. The estimated relapse rate per 1,000 patient-years was 1.55 for PB and
      0.41 for MB respectively.

PMID- 8996999
TI  - Gallbladder contraction capacity in response to liquid fatty meal: a real time
      ultrasonographic study.
AB  - Gallbladder contraction in response to a liquid fatty meal was studied in a
      hundred consecutive adult Thai subjects by using an ultrasound machine. None of
      them had clinical evidence of hepato-biliary and gastric diseases. The
      gallbladder sizes were detected at the fasting stage and after taking a liquid
      fatty meal (250 ml of milk) at 30, 60, 90 and 120 minutes respectively. The
      gallbladder size was measured by two methods, the surface area (SA) along its
      longitudinal plane and gallbladder volume (VOL). The percentage of maximal
      reduction of gallbladder size in each individual was considered as the
      gallbladder contraction capacity. The average contraction capacity in this group
      was 57.88% +/- 12.38% by SA or 74.47% +/- 9.96% by VOL. The variation of
      gallbladder contraction capacity in this population was found to have a normal
      curve distribution. The maximal contractions were found mostly (69%) at 60
      minutes and 93% of subjects had maximal contractions within 90 minutes. There was
      no difference in gallbladder contraction capacity between males and females and
      also among different age groups. The tenth percentile of gallbladder contraction
      capacity was 41.12% by SA or 61.82% by VOL. We propose that these should be
      considered as the lower limit of normal gallbladder contraction capacity after
      taking 250 ml of liquid fatty meal. This test was simple, safe and easily
      measured. This may provide useful basic information for further functional study
      of gallbladder diseases.

PMID- 8997000
TI  - Granulosa cell tumor of the ovary.
AB  - From January 1984 to December 1994, 36 women with granulosa cell tumors of the
      ovary were treated at Maharaj Nakorn Chiang Mai Hospital, which accounted for 5.8
      per cent of all 620 ovarian malignancies treated at this institute. Twenty
      patients were in stage I, 2 in stage II, 11 in stage III and the remaining 3
      cases were in stage IV. Most patients had unilateral ovarian involvement while 6
      (16.7%) had bilateral involvement. The diameter of the tumor ranged from 4 to 30
      cm with the median of 14 cm. Treatment consisted of hysterectomy and bilateral
      salpingo-oophorectomy followed by chemotherapy in most cases. To date 10 patients
      have no evidence of disease while 9 died of the disease, others were lost to
      follow-up. The 5-year survival was 94 per cent in the early stages compared to 25
      per cent in advanced stages. The overall survival rate was 62.7 per cent for all
      stages.

PMID- 8997001
TI  - Cytosol cathepsin D in Thai women with breast cancer.
AB  - The necessity of screening high-risk patients with breast cancer who may require
      more intensive systemic therapy especially in the node negative subgroup was
      generally accepted. Cathepsin D, an estrogen induced protease, has been shown to
      be implicated in the proliferation and invasion of breast cancers. Retrospective
      assessment of cytosol cathepsin D in 151 primary breast cancers was done together
      with ER, PR and other clinico-pathological parameters. No significant
      relationship was shown between cathepsin D concentrations or cathepsin D status
      using median value of 56 pmol/mg protein as cutoff level with most studied
      parameters. High cathepsin D status was found in 47 per cent of patients with
      fibrocystic disease of breast and 30 per cent in node-negative, ER-PR negative
      tumors. Survival analysis after 5 or 10 year follow-up and evaluation in a larger
      scale are necessary before including cytosol cathepsin D measurement as a routine
      clinical investigation for breast cancers.

PMID- 8997002
TI  - Evaluation of five commercial kits for free thyroxine estimation by comparison
      with equilibrium dialysis method in nonthyroidal illness.
AB  - Five commercial kits for estimating FT4 in serum of 59 euthyroid control and 38
      patients with severe NTI were studied: one non analog method (Gammacoat two step
      RIA, Clinical Assay) and four different analog methods (Amerlex-M RIA, Amersham;
      Enzymun test competitive enzyme immunoassay, Boehringer Mannheim; Amerlite
      chemiluminescence immunoassay, Kodak Clinical Diagnostics; Berilux
      chemiluminescence immunoassay, Behring) compared with equilibrium dialysis (Eq)
      method. Serum FT4 estimates in NTI patients measured by all commercial kits in
      this study yielded results comparable with those by equilibrium dialysis. The
      proportions of serum FT4 values concordant with FT4 (Eq) in each kit were 76.3,
      76.3, 76.3, 68.4 and 78.9 per cent respectively. The percentage of NTI patients
      who had serum FT4 values lower than the reference levels of the methods used were
      21.2, 26.3, 7.9, 15.8, 18.4 and 18.4 per cent respectively. No patient with low
      serum FT4 (Eq) level had subnormal or high serum TSH value. However, 4 out of 6
      patients with high serum FT4 (Eq) values had depressed serum TSH values. All of
      them also had elevation of serum FT4 estimates measured by all kits. Serum FT4
      estimates measured by all methods correlated well with FT4 (Eq) levels within the
      NTI group.

PMID- 8997003
TI  - Clinical training opportunities for Thai medical graduates in the United States.
AB  - There are many opportunities for a foreign medical graduate to receive graduate
      medical education in the US. It is unclear whether the chance is increasing or
      decreasing. Careful planning requires around a year in advance.

PMID- 8997004
TI  - Bullet embolus to the right pulmonary artery after abdominal gunshot wound with
      "piggyback bullet".
AB  - This report describes a 17-year-old man with piggyback bullets to the abdomen
      followed by bullet embolization to the right pulmonary artery. The first bullet
      was removed from the abdomen while the second missile in the lung was left
      intact. We believe this is the first case in Thailand of a bullet embolus
      resulting from piggyback bullets.

PMID- 8997006
TI  - Primary tumors of the mediastinum: 190 cases analysis (1975-1995).
AB  - A series of 190 patients with primary mediastinal tumors have been reviewed,
      typing of the tumors is according to pathological findings. The most common type
      of primary mediastinal tumors in this study was tumors of germ cell origin which
      comprised 38.9 per cent of total cases. Most patients were adults with a median
      age of 33.1 years and male to female ratio was 1.24:1. The characteristic of each
      type of tumor has been discussed. The common presenting symptoms were dyspnea,
      chest pain, and coughing, hemoptysis may occur in some cases. Only 7.9 per cent
      of cases were asymptomatic and all were discovered during the so-called "routine"
      chest X-ray examination. The diagnosis can be reached by the radiographic finding
      of mediastinal shadows. Bronchoscopy is commonly valuable to confirm external
      compression of the trachea and bronchi as well as revealing the invasion of the
      mediastinal tumors into the bronchial lumen. Pathological findings of the tissue
      sections obtained from fine needle aspiration or biopsy, as well as surgical
      specimen can provide the definite diagnosis and classification of the tumors. The
      benign tumors were successfully removed by surgery. As some types of malignant
      tumors are either chemosensitive or radiosensitive; chemotherapy and/or
      radiotherapy carries a potential survival benefit and should be incorporated into
      the multimodality approach to prolong disease-free survival.

PMID- 8997005
TI  - Haemostatic abnormalities in patients with liver disease associated with viral
      hepatitis.
AB  - Clinical and laboratory findings were studied in 56 patients with liver disease
      (10 acute hepatitis, 10 fulminant hepatitis and 36 cirrhosis). Spontaneous
      bleeding occurred in 19 patients (8 fulminant hepatitis, 11 cirrhosis) and
      another 8 cirrhotic patients had variceal bleeding. There were 22 deaths (36%),
      12 of these patients had spontaneous bleeding. Depletion of antithrombin III (AT
      III) occurred in fulminant hepatitis (mean +/- S.D. = 27 +/- 16%) and cirrhosis
      (49 +/- 23%) but thrombin-antithrombin III complexes (TAT) were significantly
      higher in the former (45 +/- 22 vs 8.6 +/- 7.0 ng/ml; p = 0.006). Within
      subgroups of cirrhosis (with or without spontaneous bleeding or with variceal
      bleeding), there were no significant differences in levels of AT III or TAT. Of
      all patients, those with spontaneous bleeding had persistently lower AT III
      levels but had variable changes of other coagulation parameters (PT, PTT, TT,
      FDP, fibrinogen and platelet counts). This study showed that coagulopathic
      consumption is an important cause of AT III deficiency in fulminant hepatitis but
      not in cirrhosis. Serial changes in AT III levels correlated with bleeding risk
      in patients with liver disease.

PMID- 8997007
TI  - Immediate angioplasty results of total coronary artery occlusion in Thai
      population.
AB  - Attempted angioplasty of totally occluded vessels may be done. However, a lower
      success rate is expected compared to those with subtotal occlusion. The
      complication rate is comparable to that of partial occlusion in experienced
      hands.

PMID- 8997008
TI  - Experience of the first 60 cases of intracoronary stent placement.
AB  - In conclusion, elective stent placement, compared to angioplasty, has a higher
      clinical success rate. However, in our early experience major complications did
      occur.

PMID- 8997009
TI  - Cytochemical and immunological phenotying of acute nonlymphoblastic leukemia in
      Thai patients.
AB  - Using morphology and cytochemical reaction, we could subclassify-according to FAB
      classification, 51 of our 56 cases of acute nonlymphoblastic leukemia (ANLL) as
      M1-M5. Five cases were undifferentiated. Using the immunophenotypic method, we
      could subclassify 51 of these patients as M1-M4. In addition, 3 cases of
      undifferentiated leukemia by the prior method were each classified as M1, M3, and
      myelo-megakaryoblastic leukemia. Correlation of ANLL subtype classification
      according to each method was not good. However, combination of both methods,
      using immunophenotypic analysis as a supplement would better subclassify the
      disease. One of the remaining 2 cases of undifferentiated leukemia was also shown
      to be myelo-megakaryoblastic leukemia by a positive platelet peroxidase reaction
      by ultrastructural cytochemistry. Thus, combination of these 3 methods could
      diagnose and subclassify 55 of the 56 cases (98%) of our ANLL patients.

PMID- 8997010
TI  - Immunohistochemical detection of c-erbB-2 oncoprotein in patients with breast
      cancer.
AB  - Using a polyclonal antibody against the c-erbB-2 gene product, an
      immunohistochemical study on the expression of c-erbB-2 oncoprotein was performed
      in routine formalin-fixed, paraffin-embedded tissue sections from 119 patients
      with primary breast cancer. Overexpression of c-erbB-2 protein was detected in 35
      cases (29%). There was a strongly negative association between c-erbB-2 protein
      overexpression and estrogen receptor status (p < 0.001). Expression of c-erbB-2
      protein was found to be related to clinical stage and tumor size (p < 0.05) but
      not to the number of involved nodes or age of patients at diagnosis. In addition,
      this study demonstrated that the c-erbB-2 protein over-expression was an
      effective independent prognostic indicator in patients with breast cancer.

PMID- 8997011
TI  - Simple and sensitive test for thyroid hormone autoantibodies.
AB  - We presented a simple and sensitive test for thyroid hormone autoantibodies. The
      normal range for T4 and T3 autoantibodies in Thai people considering mean +/- 3
      S.D. were 1.8-9.4 per cent and 3.1-8.6 per cent, respectively. Although positive
      low titer of thyroid hormone autoantibodies had almost no interference of thyroid
      hormone levels, high titer might cause great interference. This method can be
      used for screening patients who have unexpectably high levels of serum T4, T3 or
      discrepancy between thyroid hormone levels and clinical findings.

PMID- 8997012
TI  - Comparative study of antacid and sucralfate suspension for acute upper gastro
      intestinal hemorrhage in Chaiyaphum Hospital, Thailand.
AB  - A comparative study using antacid and sucralfate suspension in the treatment of
      upper G.I. hemorrhage showed that bleeding stigmenta occurred less in the
      sucralfate group than in the antacid group in a statistically significant number.
      Sucralfate therefore is an alterative preferable choice in the treatment of UGH.

PMID- 8997013
TI  - Distribution of HLA-A and B antigens in northeastern-Thais.
AB  - The phenotype and gene frequencies of HLA class I were studied in the
      Northeastern Thai population. Blood samples were collected from 100 unrelated
      healthy Northeastern Thais. HLA-A and B antigens were typed by using the standard
      microlymphocytotoxicity test. Twelve HLA-A and twenty-five HLA-B antigens were
      found in this population. HLA-A2, A24, A11 and the HLA-B46, B15, B22 antigens are
      commonly found in this group. Linkage disequilibrium analysis indicated the
      existence of fifteen haplotypes. The HLA-A2, B46 haplotype was the most common.
      These results will be useful for further studies in anthropology, organ
      transplantation and MHC associated disease in Northeastern Thais.

PMID- 8997014
TI  - Some aspects of citrate metabolism in renal-stone patients from northeastern
      Thailand.
AB  - In our previous nephrolithiasis studies in the northeast region of Thailand,
      hypokaliurea and hypocitraturia were the 2 most commonly encountered metabolic
      abnormalities. This led us to believe that people prone to forming renal-stones
      in this area were in a state of potassium depletion, a condition which probably
      caused the low urinary excretion of citrate. Further studies on some aspects of
      citrate metabolism in these subjects were carried out. Two groups of adult male
      subjects were included in the study protocol. Group 1 consisted of 20 urban
      dwellers who were used as normal controls, and group 2 was comprised of 36 renal
      stone patients residing in rural villages outside the municipal area. Fasting
      clotted venous blood and one 24-hour urine specimens were collected and analyzed
      for creatinine, citrate, calcium, phosphate, magnesium, sodium, potassium,
      chloride, bicarbonate and uric acid. Values for: creatinine and citrate
      clearances, the filtered load of citrate and the tubular reabsorption of citrate
      were then calculated. The results showed that, for both groups, the
      concentrations of most of the above parameters were within the normal ranges both
      serum and urine. An exception to this was that the levels of serum potassium and
      of urinary excretions of sodium, potassium and citrate in people in group 2 were
      significantly less than those in group 1 (p < 0.005, p < 0.001, p < 0.001 and p <
      0.0001, respectively). With respect to citrate metabolism, while the serum
      citrate levels and the filtered load of citrate were not different between the 2
      groups, the average percentage of renal tubular reabsorption of group 2 (95 +/-
      1.1%) increased significantly (P < 0.0001)in comparison to group 1 (85 +/- 1.6%).
      Moreover when results from both groups were combined, a significant negative
      correlation between the renal tubular reabsorption of citrate and the urinary
      excretion of potassium was clearly seen (r = 0.4001, p < 0.007). Our data
      suggests that potassium depletion may affect the renal tubular cells in some
      manner which, consequently, causes an increase in renal tubular reabsorption of
      citrate. The final outcome of these changes in these renal stone subjects was
      hypocitraturia.

PMID- 8997015
TI  - Hepatocellular carcinoma having progressive dyspnea as clinical presentation.
AB  - Hepatocellular carcinoma (HCC) can give multiple different initial clinical
      presentations. To the author's knowledge, however, dyspnea has not yet been
      recorded as an initial clinical presentation of HCC. A 39-year-old woman who had
      dyspnea for 2 months because of HCC is, therefore, reported herein. A chest X-ray
      revealed reticulonodular infiltration of lungs which led to antituberculous
      treatment. She died 3 months after initial dyspnea. An autopsy demonstrated a
      HCC, 1.5 x 2 x 2 cm, at the edge of the left lobe of the liver with widespread
      intravascular metastases to the lungs. The patient, moreover, had hypertrophy of
      the right cardiac ventricle being compatible with cor pulmonale. These pulmonary
      and cardiac findings are regarded to have produced dyspnea in this case.

PMID- 8997016
TI  - From "Doc" on horseback to managed care--in commemoration of the 140th
      Anniversary of the Mississippi State Medical Association.

PMID- 8997017
TI  - Reflections in time--quotes from past experiences.

PMID- 8997018
TI  - What I want for Christmas.

PMID- 8997019
TI  - We will prevail.

PMID- 8997020
TI  - Sir James Young Simpson Memorial Lecture 1995. Breast cancer prevention: a
      pathologist's approach.
AB  - Few would argue that there is not substantial room for an improvement in breast
      cancer practice. It has to be borne in mind that the United Kingdom experience in
      the 1980s was a 50:50 survival to death ratio in the 10 years after diagnosis.
      Preliminary analysis of the effects of mammographic screening suggests that there
      will be a real but small fall in overall mortality. Existing practice involves
      three stages: first, the 'earliest' detection of a lump by palpation or imaging;
      second, diagnosis by histopathology; and third, treatment by surgery, etc.
      Evidence is given that the limited success of existing practice could be due, in
      part, to a failure to recognize the precancerous state of the mammary tissue as a
      whole in cancer cases; and a failure to exploit this state for earlier diagnosis.
      In support of these contentions, comparative data from the microscopy of cancer
      associated breasts and age-matched normal breast are given. There is a gross
      excess of focal hyperplasia in premenopausal cancer-associated breast tissue.
      Further, epidemiological data are consistent in that the tissue is subject to a
      sixfold increase in the risk of further primary carcinogenesis. A method is
      presented for detecting the cancer-associated breast. It exploits the breast
      menstrual cycle, a subject which is reviewed in extenso. Physiologically the
      premenopausal mammary tissue goes into a monthly pregnancy rehearsal with
      glandular proliferation and increased blood supply. The latter effects a luteal
      heat cycle, which can be measured readily by an electronic thermometric bra as
      increased breast surface temperature (1 degree C). Data are presented in terms of
      50 normal breasts and 41 cancer-associated breasts studied daily (with
      progesterone assays) for one menstrual cycle. The cancer-associated breasts
      exhibit an absent or altered response to endogenous progesterone during the
      luteal phase of the menstrual cycle. The abnormality in the luteal heat cycle is
      maximal during the few days just after ovulation. Our data indicate that a 1-h
      clinical test at this time achieves a sensitivity of 71% and a specificity of 80%
      for "clinically normal' yet cancer-associated breast tissue. Such patients would
      be candidates for increased surveillance and chemoprevention.

PMID- 8997021
TI  - Oesophagogastrectomy for carcinoma in patients under 50 years of age.
AB  - Oesophagogastrectomy for carcinoma of the oesophagus or gastric cardia has been
      reported as being associated with a poorer outcome in young adults than in older
      patients in an Oriental population. A retrospective analysis of 597 patients who
      underwent oesophagogastrectomy for carcinoma was undertaken to ascertain if
      resection in younger Scottish patients was associated with the same poorer
      outcome. Forty-seven patients aged less than 50 years were compared with 323
      patients aged 50-69 years and 227 patients aged 70 years and older. Young
      patients had a higher incidence of distal third oesophageal tumours than older
      patients, who tended to have carcinomas of the gastric cardia. There were no
      differences with regard to tumour pathology, stage, extent of resection, hospital
      mortality or survival. In Scotland, carcinoma of the oesophagus or gastric cardia
      in young adults behaves similarly to that in older patients, and survival
      following resection is independent of age.

PMID- 8997022
TI  - Colorectal cancer surgery in a district general hospital.
AB  - The purpose of our study was to audit colorectal cancer surgery in a large
      district hospital, compare our results with other series and highlight any areas
      in patient management where improvements could be made. A comprehensive audit was
      undertaken of all patients undergoing surgery for colorectal adenocarcinoma over
      a 2-year period (December 1989 to November 1991). Two hundred and twenty-two
      patients were studied. General practitioner referrals were seen within 8 weeks in
      140 (96%) of 149 cases. Delay to diagnosis was associated with barium enema
      examination. A consultant or senior registrar was present at 187 (84.2%) of
      operations, and only two (0.9%) were undertaken between 24.00 and 08.00 hours.
      For rectal tumours the ratio of anterior resection to abdomino-perineal excision
      was 2:1. Eight of nine anastomotic leaks followed low anterior resection. All
      required re-operation and three died. The overall in-hospital mortality was 17
      (7.7%). Although our results compare favourably with other published series,
      several areas for potential improvement in management have been identified.

PMID- 8997023
TI  - The management of stab wounds to the chest: sixteen years' experience.
AB  - In a retrospective review of 16 years of admissions to a regional cardiothoracic
      unit, 76 patients were admitted with stab wounds to the chest. Of these wounds,
      75% were managed conservatively with tube drainage and observation and 25%
      required surgical intervention. 5.2% were managed as emergency room
      thoracotomies, 15.8% as urgent procedures in the operating theatre and 4% as late
      procedures. The total mortality was 1.3% and was seen in the emergency room
      thoracotomy group (mortality 25%). The risk if sub-diaphragmatic injury in the
      presence of chest injury is highlighted.

PMID- 8997024
TI  - Parathyroidectomy in chronic renal failure: comparison of three operative
      strategies.
AB  - The efficacy of subtotal parathyroidectomy (n = 11), total
      parathyroidectomy+autotransplantation (n = 13) and total parathyroidectomy alone
      (n = 24) were compared in a series of renal patients with hyperparathyroidism.
      The principal indication for surgery was severe bone disease but other
      indications were uncontrolled hypercalcaemia, soft tissue calcification and
      grossly elevated parathyroid hormone (PTH) levels. The clinical success rates at
      24 months follow-up for subtotal, total plus autograft, and total
      parathyroidectomy were 100, 89 and 97% respectively. Similar improvements in
      radiological changes and alkaline phosphatase levels were seen in all three
      groups. Recurrent hyperparathyroidism was recorded in three (27%) members of the
      subtotal parathyroidectomy group and two (16%) of the patients undergoing total
      parathyroidectomy and autotransplantation. Two patients required re-exploration
      of their forearm parathyroid autograft. No patients undergoing total
      parathyroidectomy only suffered persistent or recurrent hypercalcaemia. Vitamin D
      analogue requirements rates in patients undergoing subtotal, total plus
      autotransplant, and total parathyroidectomy at 24 months were 44, 70 and 81%
      respectively. An important finding is the demonstration of residual parathyroid
      function in 14/16 patients (87.5%) undergoing total parathyroidectomy without
      autotransplantation and followed-up for 2 years.

PMID- 8997025
TI  - A prospective audit of cholecystectomy in a single health district.
AB  - Laparoscopic cholecystectomy is becoming the treatment of choice for patients
      presenting with gallstones. A prospective audit of all patients undergoing
      cholecystectomy in a single health district over a six-month period was carried
      out. The aim was to define those patients not having laparoscopic cholecystectomy
      and determine the morbidity and mortality associated with open and laparoscopic
      procedures. Cholecystectomy was performed on 173 patients; 149 operations were
      attempted laparoscopically, of which 134 were successful, giving a conversion
      rate of 10%. Elective open cholecystectomy was performed on 24 patients. Twenty
      of these patients were under the care of a consultant who only performs open
      cholecystectomy and the others were not offered a laparoscopic procedure because
      of previous abdominal operations. The median time taken for open cholecystectomy
      was significantly shorter (P < 0.05) than for laparoscopic cholecystectomy or for
      converted procedures. Laparoscopic cholecystectomy resulted in bile duct injury
      in one patient (0.7%). This study shows that the majority of patients with
      gallstones are being offered laparoscopic cholecystectomy, although some patients
      will undergo open cholecystectomy. The latter include patients under the care of
      surgeons not performing laparoscopic cholecystectomy, those presenting as an
      emergency where laparotomy is performed and those where laparoscopy is contra
      indicated. The findings of this study are probably representative of other health
      districts where a similar mix of surgical practice exists.

PMID- 8997026
TI  - Infrageniculate vein bypass graft for critical limb ischaemia: one surgeon's
      experience.
AB  - The results of 63 patients under the care of one surgeon who underwent a bypass,
      using vein, for critical limb ischaemia are presented. Thirty-two operations were
      to the crural vessels and the results are compared with those for 31
      infrageniculate femoropopliteal bypasses. All patients were entered into a graft
      surveillance programme. There were no graft failures after 1 year in the
      femoropopliteal group with primary, primary assisted and secondary patency rates
      of 86, 90 and 93% respectively at 3 years. In the femorocrural group the rates
      were 55, 60 and 64% respectively. The difference in secondary patency was
      considered statistically significant (P < 0.01). Mortality rate of the
      femoropopliteal group was 31% at 3 years compared with 53% for the femorocrural
      group (n.s.). Five patients underwent major amputation, all of whom were in the
      femorocrural group. Failures, interventions and the effect of graft surveillance
      are discussed and the high mortality rate is highlighted.

PMID- 8997028
TI  - Landmines: morality vs. expediency?

PMID- 8997027
TI  - Surgeon protection: early recognition of glove perforation using a green under
      glove.
AB  - This paper reports the use of a double gloving system, which consists of a
      standard latex over glove and a green latex under glove, and aids recognition of
      intra-operative glove perforation during trauma surgery. Recognition of
      perforation is possible due to the colour of the under glove becoming more
      visable following ingress of fluid between the glove layers. The gloves were used
      in 40 consecutive operative procedures for lower limb fracture fixation. Glove
      perforations occurred in 48% of operations. The outer glove was perforated on 26
      occasions and the under glove on two. There were no false positive colour changes
      but on one occasion no indication of perforation was visible. The rapidity and
      accuracy of colour change allowed identification of the cause of glove damage
      intra-operatively. This was most often due to powered instrumentation (58%).

PMID- 8997029
TI  - The incidence of landmine injuries in Kuito, Angola.
AB  - Angola is one of the most heavily mined countries in the world. Despite the vast
      effort made to clear landmines, very few accurate figures for casualty rates are
      available. The town of Kuito in central Angola is surrounded by minefields left
      after the 22-month siege by the rebel UNITA forces. Many are in close proximity
      to residential areas. This retrospective audit assesses the incidence of landmine
      injuries in the wake of the siege, and the levels of amputation resulting from
      these wounds. Between January and October 1995, 94 landmine injuries occurred (60
      from anti-personnel mines, 34 from anti-tank mines). Mine injuries accounted for
      11.8% of the admissions to the surgical ward of Kuito hospital, but for 20.2% of
      the total number of operations performed. The distribution of injuries between
      the sexes was roughly equal (33 males: 27 females), but women required more above
      knee amputations than men (16/20 versus 14/27). Mortality from anti-personnel
      mines was 1.7% (1/60). Seventy per cent of all lower limb amputations in Kuito
      are performed as a result of landmine injury (53/76). Landmines exert a severe
      strain on already stretched surgical services, and a significant burden of
      morbidity on the population of Kuito.

PMID- 8997030
TI  - Hand problems presenting to a district general hospital accident and emergency
      department.
AB  - An audit was carried out of 1000 consecutive patients presenting with hand
      problems to a busy district general hospital (DGH), accident and emergency
      department (A&E). Hand problems accounted for 11% of all A&E presentations. Over
      50% of cases were examined radiologically with 37% of these having positive
      findings. Most patients were male (66%) and manual workers (34%). Only 2.8% of
      patients required admission, and 50% were discharged with no follow-up. Less than
      5% were referred by their general practitioner (GP) and these patients presented
      during office hours (08.00-18.00 h). The vast majority of the presenting patients
      could have been treated in a modern, well equipped GP surgery.

PMID- 8997031
TI  - Hip ganglion: case report and review of the literature.
AB  - We present an unusual case of a ganglion of the hip. The patient presented with a
      groin mass initially thought to be inguinal lymphadenopathy, related to a scrotal
      malignant melanoma excised 2 years earlier. Five similar cases have been
      previously reported. In all cases the pre-operative diagnosis was wrong (femoral
      hernia, inguinal lymphadenopathy, inguinal abscess). Only at operative
      exploration was the correct diagnosis made. The diagnosis of hip ganglion should
      be borne in mind when a patient presents with an inguinal swelling.

PMID- 8997032
TI  - Day-case surgery in children under 2 years of age: experience in a district
      general hospital and survey of parental satisfaction.
AB  - One surgeon's experience of day-case paediatric surgery in a population aged less
      than 2 years at a district general hospital is reported. During a 6-year period
      from 1989 to 1994, 82 day-case operations were performed in 79 infants and young
      children. All children were managed by a multidisciplinary team including
      surgeon, paediatric anaesthetist and paediatric nurses. There was no mortality
      and minimal morbidity. A telephone survey of parents enquiring into satisfaction
      with all aspects of pre-, peri-, and post-operative care revealed that the
      procedures are well-accepted. The survey also showed that there was no increased
      utilization of primary health care professionals when day-case surgery is
      performed in this young age group. We conclude that paediatric day-case surgery
      is safe and well-tolerated by both infants and parents and is suitable for
      performance in non-specialist centres provided a team approach is adopted.

PMID- 8997033
TI  - Just a 'wee prick' with a needle.
AB  - Difficulty with vascular access is a common problem in neonatal medicine and
      surgery. Recent advances in parenteral therapy/nutrition and manufacture of high
      quality intravenous lines have enabled smaller infants to survive. Thus, in the
      small surgical neonate, the insertion of an indwelling intravenous long line
      (either percutaneously or at cut down) is a frequent occurrence. This procedure
      is not without its complications and it is thus necessary for the clinician
      inserting these lines to be aware of this and fully understand the regional
      anatomy of the area being used. I wish to report an unusual complication which
      posed several diagnostic and management problems.

PMID- 8997034
TI  - The use of the CO2 laser for airway maintenance in obstructive supraglottic
      carcinoma.
AB  - CO2 laser 'debulking' of obstructive supraglottic tumours is an alternative to
      tracheostomy to restore the compromised airway. Two patients have successfully
      undergone radiation therapy after laser vaporization of their large supraglottic
      tumours, and did not require tracheostomy. This technique is relatively simple,
      avoids the morbidity of tracheostomy and facilitates early irradiation.

PMID- 8997035
TI  - Suppurating facial lesions may be a sign of dental infection.
AB  - We describe three cases of chronic dental sepsis presenting with facial
      suppuration (dentocutaneous sinus). Misdiagnosis may lead to unnecessary
      morbidity. Inappropriate hospital referral wastes resources.

PMID- 8997036
TI  - Gas explosion during colonic surgery.
AB  - Explosions of the colon as a result of the use of diathermy in the presence of
      gas mixtures of oxygen, hydrogen and/or methane have been previously described in
      the literature. This danger is present during colonoscopic polypectomy as well as
      during colonic surgery. The following case is presented to alert to the potential
      hazards of bowel gas during electrosurgery.

PMID- 8997037
TI  - 'Raver's' haematuria.
AB  - Strenuous exertion is a recognized cause of haematuria but full investigation is
      still required to exclude any serious underlying pathology. Heavy exercise and
      amphetamine abuse can both cause rhabdomyolysis and acute renal failure. The
      recent popularity of 'rave parties' has highlighted these problems in young
      people who attend the all-night dance parties where a minority of them abuse
      drugs such as amphetamines. We describe a case of rhabdomyolysis following
      ingestion of amphetamines during a rave party, where the patient was diagnosed
      early, presenting acutely with frank haematuria.

PMID- 8997038
TI  - Acute scrotum: an unusual presentation of Henoch-Schonlein purpura in children.

PMID- 8997039
TI  - Myofibroblastoma: an unusual breast lump.
AB  - A case of myofibroblastoma of the breast is reported. The clinical significance
      of this entity lies primarily in its recognition as a distinctive benign
      neoplasm.

PMID- 8997040
TI  - Efficacy of urgent thoracotomy for trauma in patients attended by a helicopter
      emergency medical service.

PMID- 8997042
TI  - Assessment of pre-operative investigations of thyroglossal cysts.

PMID- 8997041
TI  - Assessment of pre-operative investigations of thyroglossal cysts.

PMID- 8997043
TI  - Opsite skin closure in day case paediatric surgery: is a subcuticular suture
      necessary?

PMID- 8997044
TI  - V-Y plasty for Dupuytren's contracture of the palm.

PMID- 8997045
TI  - A simple assessment of surgical sutures and knots.

PMID- 8997046
TI  - [Nitric oxide and the lung].
AB  - Many studies on nitric oxide (NO) as a messenger for biosignal transduction have
      recently been published. Endogenous NO is thought to play a pivotal role in
      homeostasis of the respiratory system and pulmonary circulation. As exhaled NO
      levels increase in patients with asthma or bronchiectasia, NO seems to be related
      to some pathological states in the respiratory organ. NO inhalation has been
      shown to be effective in attenuating pulmonary hypertension and desaturation in
      acute respiratory failure. Recent findings concerning NO in the lung were
      described in this review article.

PMID- 8997047
TI  - [Influence of stellate ganglion block and electrical stimulation of the stellate
      ganglion on bilateral brachial arterial blood flow--is stellate ganglion block
      effective either unilaterally or bilaterally?].
AB  - The purpose of this study was to investigate the influence of the stellate
      ganglion block (SGB), stellate ganglion electrical stimulation (SGES) and
      stellate ganglionectomy on bilateral arterial blood flows (BAF). Sixteen mongrel
      dogs were divided into two groups; a SGB group (n = 8) and a SGES group (n = 8).
      Anesthesia was induced with pentobarbital 25 mg.kg-1 and the animals were
      mechanically ventilated to maintain proper PaO2 (90-100 mmHg) and PaCO2 (35-40
      mmHg). After a thoracotomy, the SGB with 0.5% mepivacaine 1.0 ml was performed in
      the SGB group. SGES was performed at a strength of 12 volts, and at a frequency
      of 50 Hz, applied for 15 minutes and then 15 minutes after the SGES, stellate
      ganglionectomy was performed in SGES group. In the SGB group, BAF in the blocked
      side increased significantly but BAF in the contralateral side decreased
      significantly after SGB. In the SGES group, bilateral BAF decreased significantly
      (Lt > Rt) and after the stellate ganglionectomy, bilateral BAF increased more
      than after SGES. These results suggest that the SGB may not be effective on the
      contralateral side under normal conditions, but under the conditions of
      sympathetic stimulation, the SGB may be effective on the contralateral side.

PMID- 8997048
TI  - [Rapid induction of anesthesia with propofol--comparison with thiopental].
AB  - We investigated hemodynamic changes, induction time and the incidence of pain
      after rapid induction of anesthesia with propofol (Group P) in comparison with
      those after induction with thiopental (Group B). Anesthesia was induced with
      propofol 2.5 mg.kg-1 in Group P and thiopental 5 mg.kg-1 in Group B taking 20
      seconds. When verbal response disappeared, tracheal intubation was performed with
      suxamethonium 1.2 mg.kg-1. The incidence of pain on injection, time from the
      start of injection of the drug to the disappearance of verbal response (induction
      time), blood pressure, heart rate, and rate pressure product (RPP) were
      monitored. The pain on injection was seen in 6 of 30 patients in Group P. This
      was significantly larger compared with 3 patients in Group B. The induction time
      was not different between the two groups. One minute after intubation, blood
      pressure, heart rate and RPP were significantly higher compared with those before
      induction in Group B. These were also significantly higher than those in Group P.
      Therefore, rapid induction with propofol is more useful compared with that with
      thiopental.

PMID- 8997049
TI  - [Examples of pitfalls in statistical analysis--4: What is a type II error?].
AB  - When assessing the results of statistical analysis, we have to consider two types
      of errors, i.e., type I errors, which present the risk of erroneously judging a
      true hypothesis to be false, and type II errors, which present the risk of
      erroneously judging a true hypothesis to be true. If we use only type I errors to
      detect the significances in statistical analysis, we can not avoid making the
      erroneous judgement that a true hypothesis is false. When the results of analysis
      are not significant, we have to calculate type II errors and discuss the
      probabilities of having missed the truth. In this article, I present an example
      to illustrate two types of errors which can occur in assessing the result of
      statistical analysis.

PMID- 8997050
TI  - [Participation of anesthesiologists in the Internet].
AB  - The author classified the e-mail addresses of the mailing list "Masui Discussion
      List" users. The result indicates that the types of the participation of those
      users in the Internet are classified into the following three: (1) Use of the
      network of employment places such as universities and hospitals or their
      facilities, (2) Via the BBS (Bulletin Board System) host, and (3) Contract with a
      network service provider. The author estimates the following: Type (1) occupies
      about half of the whole types. Types (2) and (3) occupy about a quarter of the
      whole types, respectively. If the network of the employment place cannot be used
      to access the Internet, dial-up IP connection can be made by contracting with a
      network service provider. To make such a connection, a multimedia personal
      computer, dial-up IP connection software, a high-speed modem or a terminal
      adapter, and variety of Internet application software such as World Wide Web
      browser are required in addition to the telephone line (analog or ISDN).

PMID- 8997051
TI  - [Usefulness of alpha 2-adrenoceptor agonists and practical problems associated
      with their use in clinical anesthesia--1. Premedication, anesthetic adjuvants,
      and hemodynamic effects].
AB  - A great deal of new information on alpha 2-adrenoceptor agonists has recently
      been accumulated in humans; alpha 2-agonists have several beneficial actions in
      clinical anesthesia including sedative, anxiolytic as well as analgesic effects,
      improved hemodynamic stability, and etc. In the first part of this review, we
      summarized the structure, signal transmission and basic pharmacology of alpha 2
      adrenoceptor agonists (clonidine and dexamedetomidine), and evaluated their
      usefulness for premedication, and as anesthetic adjuvants as well as agents for
      stabilizing circulation in the clinical settings. In addition, we referred to
      practical problems associated with their use.

PMID- 8997052
TI  - [Cesarean section in a morbidly obese parturient under epidural anesthesia].
AB  - A 26-yr-old morbidly obese parturient with a body mass index of 62 kg.m-2
      underwent elective cesarean section for preeclampsia under epidural anesthesia.
      The distance between the skin and the epidural space was about 9 cm at the L3-4
      interspace via mid approach. Epidural catheter was inserted 5 cm cephalad in the
      sitting position and a bolus of 17 ml of mepivacaine 1.5% was given in the supine
      position. The T5 level of analgesia was obtained 10 min later. Forty minutes
      after the start of the surgery, a female newborn weighing 3,206 g was delivered
      with an Apgar score 8 at 1 min and 9 at 5 min. Throughout the surgery, sufficient
      analgesia was obtained and any complications such as severe hypotension and
      respiratory depression did not develop. Postoperative pain was relieved
      sufficiently with a continuous epidural infusion of 0.25% bupivacaine at a rate
      of 0.5 ml.h-1 for two days. Both maternal and neonatal postpartum courses were
      uneventful. In conclusion, elective cesarean section in a morbidly obese
      parturient was successfully managed with epidural anesthesia. This indicates that
      an elective cesarean section under epidural anesthesia reduce the risk of
      perioperative complications in a morbidly obese parturient.

PMID- 8997053
TI  - [Spinal anesthesia with 2% plain lidocaine for ultrasonically guided vaginal
      oocyte retrieval].
AB  - Spinal anesthesia with 3 ml of 2% plain lidocaine was administered to 10 women
      for ultrasonically guided vaginal oocyte retrieval. Spread of anesthesia was
      assessed by skin vasodilatation, change of skin texture, loss of goose flesh
      reflex, and loss of cold as well as pin-prick sensation, and we studied time to
      complete motor block, time to two-segment regression, time to full motor and
      sensory recovery, ambulation time, haemodynamic parameters, and postoperative
      complications. The highest sensory block assessed by pin-prick was up to Th 8.3
      +/- 3.4 10 min following spinal anesthesia. All patients had complete motor block
      and this was achieved at 9.0 +/- 1.7 min. Times to two-segment regression, full
      motor and sensory recovery, and ambulation were 84.5 +/- 31.0, 147.5 +/- 24.7,
      176.5 +/- 23.2, and 203.3 +/- 50.0 min, respectively. No serious side effects
      were observed during the operation and postoperatively. We concluded that 3 ml of
      2% plain lidocaine provided adequate spinal anesthesia for ultrasonically guided
      vaginal oocyte retrieval.

PMID- 8997054
TI  - [Effects of continuous epidural administration of fentanyl and morphine on
      postcesarean pain].
AB  - We studied the effects of continuous epidural administration of fentanyl and
      morphine with bupivacaine for management of postcesarean pain. Eighteen patients
      received either bolus epidural administration of fentanyl 100 micrograms or
      morphine 3 mg with 0.5% bupivacaine 4 ml, followed by continuous infusion of
      fentanyl 33 micrograms.ml-1 with 0.17% bupivacaine or morphine 0.21 mg.ml-1 with
      0.17% bupivacaine for 48 hours, respectively. Pain score was assessed at 0 h,
      12h, 24h and 48h after leaving the operating room. Pain score increased
      significantly and progressively in the fentanyl group. In all cases pruritus was
      noted. Severe pruritus was observed in the morphine group significantly more than
      in the fentanyl group. The current results indicate that morphine may be
      preferable to fentanyl for postcesarean pain control using the present opioid
      doses.

PMID- 8997055
TI  - [Respiratory management after closure of a bronchial-fistula with an omental
      pedicled gastric flap].
AB  - A 56-year-old female, after closure of a bronchial-fistula with an omental
      pedicle gastric flap, underwent controlled ventilation for two weeks in order to
      stabilize the flap. We suspended the administration of vecuronium once a day and
      examined the plasma concentration of vecuronium when a twitch response appeared.
      During the two weeks of ventilation, plasma concentration of vecuronium was
      maintained at low doses by adjusting the daily dose of vecuronium infusion.
      However, the suspended period of vecuronium infusion was prolonged gradually and
      the patient care such as tracheal suction and position changing became
      restricted. In addition, we have to care for the infection and a mental injury.

PMID- 8997056
TI  - [Pediatric fiberoptic bronchoscopy via the laryngeal mask airway].
AB  - Fiberoptic bronchoscopy was performed on 11 children aged from 6 months to 3
      years and weighing between 2.1 and 12.5 kg using the laryngeal mask airway (LMA).
      The LMA allows observation of subglottic stenosis which can not be seen under
      tracheal intubation. The smaller prototype of the fiberoptic bronchoscope whose
      diameter is 1.8mm has no provision for angulation at the tip. However, using the
      LMA as a guide it was easy to reach the subglottic stenosis even using this
      smaller bronchoscope.

PMID- 8997057
TI  - [A hematologic coagulation monitoring system for bedside use].
AB  - Perioperative hemorrhage in patients undergoing surgery is a major cause of
      morbidity and mortality. DRIHEMATO SYSTEM COAG-1 can detect prothrombin time
      (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) easily.
      We combined this monitor with platelet count (PLT), activated clotting time (ACT)
      and thromboelastography (TEG) and devised a hematologic monitoring system for
      bedside use. This study of 10 adults undergoing cardiopulmonary bypass was
      conducted to determine the utility of this monitoring system. The specificity for
      lotting abnormality of this monitoring system included the following values; PT =
      88%, FIB = 100% and TEG = 67%. This study suggests that this monitoring system
      may be useful in early diagnosis and treatment of postoperative coagulopathy.

PMID- 8997058
TI  - [Evaluation of the bite block wedged between the maxillary and mandibular
      molars].
AB  - The purpose of this study was to compare our original bite block (T-X Block)
      wedged between the maxillary and mandibular molars, with the standard gum bite
      block, in 200 patients whose tracheas were intubated. During emergence from
      isoflurane anesthesia, no trouble occurred in T-X Block group (n = 100). On the
      other hand, lip damage and ejection of the bite block were found in 11 and 10
      cases, respectively, in gum bite block group (n = 100). As another study, an
      opening between the maxillary and mandibular incisor edges was measured with T-X
      Block placed in twenty patients under general anesthesia. The inter-incisal
      distances in one way of using it as a smaller wedge and in the other way as a
      bigger one were 21.6 +/- 2.4 and 25.2 +/- 2.6 mm, respectively. Those values were
      significantly larger than thickness of the gum bite block. T-X Block is very
      useful because its use causes no complications and makes it easier to insert a
      naso-gastric tube as well as to clean the oral cavity with suction by giving a
      larger opening of the mouth.

PMID- 8997059
TI  - [A case of the foreign body due to "coring"].
AB  - A case of the foreign body due to coring from the rubbercap of a 50 ml Diprivan
      vial was reported. Furthermore, how the fragment is made and how to decrease the
      incidence are discussed. The incidence of coring should decrease by improvement
      of the needle and by sticking vials vertically. However, even if the improvement
      of the rubber, needles and sticking technique is achieved, the occurrence of
      coring can not be eliminated completely. The best way to avoid coring will be to
      furnish "50 ml syringes containing Diprivan" commercially.

PMID- 8997060
TI  - Small and special: the development of hospitals for children in Victorian
      Britain.

PMID- 8997062
TI  - Workforce issues pressure IMGs.

PMID- 8997061
TI  - Patient record legality issues.

PMID- 8997063
TI  - David H. Janda, MD. A national leader in preventing sports injuries.

PMID- 8997064
TI  - Valuing physician practices.

PMID- 8997065
TI  - Medicaid capitation.

PMID- 8997066
TI  - Restructuring Michigan health care.

PMID- 8997068
TI  - Young fathers need role models.

PMID- 8997067
TI  - From PSP to capitation.

PMID- 8997069
TI  - Change an open invitation.

PMID- 8997070
TI  - Multisystem granulomatous disorders.

PMID- 8997071
TI  - The ethics of managed care.
AB  - Ethical concerns relating to managed care discussed in this essay include
      incentives to underutilize services, delays in care, postponement of consultation
      or hospitalization, gatekeeping, patient satisfaction, physician satisfaction,
      and information disclosure. Because managed care is here to stay, physicians and
      patients must learn to understand it and develop methods to work with it,
      preserving the overriding principle that the physician's first obligation is to
      be the patient's advocate. Physicians must continue to practice good medicine,
      eliminate that which is unnecessary, and be conscious of the need to contain
      costs.

PMID- 8997072
TI  - The role of sex steroids in the pathogenesis and maintenance of benign prostatic
      hyperplasia.
AB  - BACKGROUND: It has long been suspected that sex steroids play a key role in the
      pathogenesis of benign prostatic hyperplasia (BPH). Prostatic diseases do not
      occur in males castrated before puberty or in males with heritable disorders of
      androgen production or action. Both estrogens and androgens have been shown to
      induce BPH in experimental animals. METHODS: Clinical studies utilizing hormonal
      therapies to treat BPH were reviewed. Studies that used total medical castration
      therapy via the use of a long-acting gonadotropin-releasing hormone (GnRH
      agonist), partial androgen blockade via the use of the 5 alpha-reductase
      inhibitor finasteride, and estrogen blockade (via the use of aromatase
      inhibitors) were analyzed. RESULTS AND CONCLUSIONS: Both the GnRH agonists and
      finasteride result in prostatic size reduction and alleviate symptoms in some
      patients. Both therapies are more effective in men with larger prostates (> 40
      cc). Finasteride is less efficacious in terms of size reduction than the GnRH
      agonists but also has fewer side effects. To date, clinical trials with aromatase
      inhibitors have not yielded dramatic positive results in the treatment of BPH.

PMID- 8997073
TI  - [Prognostic significance of carcinoma in situ and epithelial dysplasia
      accompanying bladder cancers].
AB  - PURPOSE: We determined whether patients with bladder cancers accompanied by
      carcinoma in situ (CIS) or epithelial dysplasia carry a poor prognosis. MATERIALS
      AND METHODS: The resected bladders from 57 patients with a bladder cancer were
      step-sectioned. The stained specimens underwent microscopic examination and the
      extent of CIS and epithelial dysplasia was mapped out. The 57 patients were
      followed up for 5 to 10 years and the cumulative survival rates were calculated.
      RESULTS: Gross tumors were accompanied by CIS in 29 (51%) patients and by
      epithelial dysplasia in 52 (91%) patients. The survival rates did not differ
      significantly between the presence and absence of the accompanying mucosal
      lesions. However, the cancer specific survival rates were higher in patients with
      accompanying CIS located away from the gross tumor than in patients with CIS
      located adjacent to the gross tumor (p = 0.04). In patients with a non-papillary
      bladder cancer the survival rates tended to be higher when accompanying
      epithelial dysplasia accounted for over 3% of the whole mucosal area than when it
      accounted for less than 3% (p = 0.09). CONCLUSIONS: These results suggest that
      the presence of accompanying CIS or Epithelial dysplasia does not indicated a
      poor prognosis, and may indicate a favorable prognosis in patients with a non
      papillary bladder cancer.

PMID- 8997075
TI  - [The efficacy of ATP sensitivity assay on intravesical prophylactic instillation
      for superficial bladder cancer].
AB  - BACKGROUND: The object of this study is to evaluate the usefulness of the ATP
      sensitivity assay for appropriate selection of anticancer drugs for prophylactic
      bladder instillation therapy in patients with superficial bladder cancer.
      METHODS: The ATP assay was performed using the method reported previously. The
      anticancer drugs examined were ADM, MMC, THP-ADM and EPI. The 5-year rate of non
      recurrence in group A (32 cases) which had been treated using the results of ATP
      assay, was compared with that of group B (37 cases), for which the ATP assay was
      not performed. RESULTS: The most sensitive anticancer drug was THP-ADM. The 5
      year rate of non-recurrence in group A (80.9%) was significantly higher than that
      in group B (39.4%) (p < 0.001). Tumor recurrences in group A was observed within
      2 years post-operatively in all cases. When the ATP assay was re-performed in 3
      cases with recurrent disease, altered antitumor sensitivity was observed.
      CONCLUSION: These findings suggested that ATP assay was useful for choosing
      effective anti-cancer drugs for prophylactic instillation, especially for
      patients with primary or solitary tumor, grade 2 disease or tumor of a certain
      size (> or = 1 cm). It also appeared that the ATP assay should be performed for
      patients with primary superficial bladder cancer as a screening test for the
      selection of drugs for prophylactic instillation therapy.

PMID- 8997074
TI  - [Study on the sclerosing agent for the treatment of simple renal cysts].
AB  - BACKGROUND: The objective of this study is to evaluate the sclerosing agents for
      simple renal cysts. METHODS: Thirty-three renal cysts of 30 patients were treated
      by injection of sclerosing agents with the guidance of ultrasonography. Among
      them, 22 were treated with ethanol, and 11 with minocycline-hydrochloride (MINO).
      RESULTS: Clinical efficacy rates and volume reduction rates in each treatment
      group of ethanol or MINO, were 100% and 90.9%, and 91.2 +/- 13.1% (mean +/- SD)
      and 83.2 +/- 28.5%, respectively. Although several complications including pain
      and intoxication were observed in ethanol (47.4%), no complications were observed
      in MINO. CONCLUSION: The instillation of MINO into renal cysts is an effective,
      safe and simple treatment. It is thought that it can be the first choice of
      treatment for simple renal cysts.

PMID- 8997076
TI  - [Results of genitoplasty for virilized genitalia of 41 females with congenital
      adrenal hyperplasia].
AB  - OBJECTIVE: The results of genitoplasty performed at our clinic for 41 female
      patients with congenital adrenal hyperplasia (CAH) were reviewed. PATIENTS: Among
      57 females with CAH (56 with 21-hydroxylase deficiency and 1 with 11 beta
      hydroxylase deficiency) diagnosed between 1961 and 1995, 41 underwent
      genitoplasty. For the rest of 16 patients, 1 received already clitorectomy, 11
      (19%) needed no surgical reconstruction, 2 died before surgery, and 2 are in a
      waiting list for surgery. RESULTS: According to Prader's classification of
      virilized genitalia, 41 patients who received surgery included 8 of type I, 10 of
      type II, 17 of type III, and 4 of type IV. There was no patients of type V, and 2
      were not classified because of previous surgery. Four patients underwent
      genitoplasty 7 times in total before visiting us. The age receiving initial
      genitoplasty at our clinic ranged from one year and 9 months to 20 years (median:
      4 years and 5 months). Follow-up period averaged 17 years with the range of 2
      months to 33 years. For enlarged clitoris, clitorectomy (amputation of clitoris)
      was carried out for 22 patients before 1975 and corporal resection for 17 after
      1975. Two patients manifested recurrence of clitoromegaly after the surgery
      because of either incomplete resection of the clitoris or patient's ignorance of
      taking glucocorticoid regularly. Thirty-six patients needed labiovaginoplasty.
      Simple midline cutback was performed for 6 patients and Y-V plasty (skin flap
      labiointroitoplasty) for 30. Vaginal orifice was not identified in 5 patients at
      the initial surgery. Two patients received successful second introitoplasty at
      the older age than 10. Post-operative stenosis of vaginal orifice was confirmed
      in 6 patients and 3 underwent second introitoplasty. Among 23 patients older than
      25 years at present, 7 got married and 4 raised 6 children with assistance of
      Caesarian section. CONCLUSIONS: Most of female patients with CAH needed genital
      plastic surgery including clitoroplasty and labiovaginoplasty. Corporal resection
      for enlarged clitoris with sufficient hormone therapy brought a satisfactory
      result. Y-V plasty for labiovaginoplasty proved to be an excellent method,
      especially from cosmetic viewpoint, but remained some problems as one stage
      operation including difficult identification of vaginal orifice and post
      operative stenosis of introitus in some patients.

PMID- 8997077
TI  - [Evidence for association between renal cell carcinomas and renal cystic
      diseases: nationwide survey in Japan].
AB  - OBJECTIVE: A scanty evidence previously reported regarding renal cell carcinomas
      occurring in association with renal cystic diseases prompted us to conduct a
      nationwide survey in July 1991. METHODS: A total of 507 hospitals responded to
      the questionnaire inquiring the clinical and pathological characteristics of
      renal cell carcinoma associated with renal cystic diseases over the previous 2
      years. RESULTS: Renal cystic diseases were identified in 223 (3.9%) of 5,721
      patients with renal cell carcinoma. The patients consisted of 181 men and 42
      women who had a mean age of 55.2 +/- 12.5 years (SD). The renal cystic diseases
      comprised simple renal cysts in 72 patients (32%), acquired cystic diseases of
      the kidney (ACDK) in 62 (28%), cystic renal cell carcinoma in 56 (25%),
      multilocular renal cysts in 20 (9%), polycystic kidney in 3 (1.3%), miscellaneous
      cysts in 9 (4.0%), and unspecified cysts in 1 (0.4%). Simple renal cysts were
      more common in older patients, while ACDK and multilocular cysts were more
      predominant in younger patients. They included 71 dialysis patients (32%), of
      whom 62 (87%) had ACDK. Renal cell carcinoma occurred bilaterally in 12 patients
      (17%) on dialysis. Young male patients over a longer dialysis period were more
      susceptible to renal cell carcinoma. Low stage tumor, papillary type and granular
      cell subtype were more common in those on dialysis than in those without
      dialysis. In consideration of the Japanese general and dialysis population, we
      confirmed that dialysis patients with ACDK are more susceptible to renal cell
      carcinoma and those with polycystic kidney are less so. CONCLUSION: Renal cystic
      diseases may be associated with about 4% of renal carcinoma. Young male patients
      over a longer dialysis period who are diagnosed to have renal cysts should be
      regularly and closely followed by imaging study.

PMID- 8997078
TI  - [Experience of 28 deliveries in 21 kidney transplant recipients].
AB  - BACKGROUND: Risk factors to induce graft dysfunction during pregnancy in kidney
      transplant recipients were studied. METHODS: A total of 28 deliveries from 21
      female kidney transplant recipients were analyzed. RESULTS: All recipients were
      maintained on either azathioprine-based (n = 17) or cyclosporine-based (n = 11)
      immunosuppressive regimens. Graft dysfunction (creatinine clearance < 40 ml/min)
      occurred in 8 cases (8 patients) during pregnancy. No acute rejection, however,
      could be observed. In a case-controlled study comparing a group with graft
      dysfunction vs. a group with good graft function, there were significantly
      differences in the incidence of the cases with pre-existing hypertension (62.5%
      vs. 10.0%), the age of the grafted kidney (58.1 vs 47.6 year), the maternal
      anemia (Hb: 10.3 vs. 11.8 g/dl) and the creatinine level (1.4 vs. 1.0 mg/dl) at
      the first trimester. These findings suggested that poorer graft function had been
      underlying before pregnancy and that additional loading of the pregnancy reduced
      further graft function, while the deterioration would be recovered after delivery
      in all cases except one case. CONCLUSION: Risk factors to induce graft
      dysfunction during pregnancy are as follows. 1) high age of the grafted kidney (>
      50 year), 2) pre-existing hypertension, 3) maternal anemia (Hb: < 11 g/dl) and 4)
      high creatinine level (> 1.3 mg/dl) at the first trimester.

PMID- 8997079
TI  - [Regional and chronological differences of urogenital cancer deaths in Japan].
AB  - PURPOSE: We investigated the changing patterns of urogenital cancer deaths during
      the past 22 years in Japan. METHODS: We analyzed patients that died from cancer
      of the prostate, bladder and kidney between 1973-1994. Age-adjusted death rates
      (adjusted to the world population), standardized mortality ratios (SMR) according
      to each prefectures and age-specific death rates for each types of cancer were
      calculated and changes in these patterns were analyzed. RESULTS: Age-adjusted
      death rates for cancer of the prostate increased from 2.29 in 1973 to 4.36 in
      1994, a 1.9-fold increase. Death rates for cancer of the bladder were stable in
      males and declined in females. Death rates for cancer of the kidney (15 years or
      older) increased from 1.45 in 1973 to 2.72 in 1994, a 1.9-fold increase in males,
      and tended to increase in females as well. In the SMR analysis by prefecture,
      distribution in 1973-84 (former period) and that in 1985-94 (later period) were
      similar, and characteristic features were observed for each type of cancer. Age
      specific death rates for cancer of the prostate and bladder rose by an index
      power of age, but that for cancer of the kidney reached a plateau or decreased
      after an index power increase to a certain age. The rate of increase in age
      specific death rates (later period/former period) rose according to age,
      especially 70 years or older, in cancer of the prostate and kidney in both males
      and females. However, age-specific death rates in the later period from cancer of
      the bladder was higher only in patients 85 years or older, but was lower in other
      age groups. CONCLUSIONS: Death rates for cancer of the prostate and kidney (15
      years or older) tended to increase, while that of the bladder remained stable or
      decreased. It is expected that detection and treatment of these disease can be
      improved by utilizing these epidemiologic information.

PMID- 8997080
TI  - [Diagnostic values and limitations of conventional urodynamic studies
      (uroflowmetry.residual urine measurement.cystometry) in benign prostatic
      hypertrophy].
AB  - PURPOSE AND METHODS: Diagnostic values and limitation of conventional urodynamic
      study (UDS) were assessed in 380 patients with benign prostatic hypertrophy
      (BPH), in terms of uroflowmetry, measurement of postvoid residual urine and
      cystometry. RESULTS: Maximum and average flow rate on uroflowmetry improved with
      increasing voided volume. Neither maximum nor average flow rate correlated with
      size of the prostate, subjective symptom (International Prostate Symptom Score)
      and bothersomeness for prostatism. Pre-TUR maximum flow rate did not predict
      outcomes on postoperative flow rate and surgical treatment failures. Uroflowmetry
      did not differentiate between obstruction and weakness of detrusor contraction.
      The intraindividual variation of postvoid residual urine was great and the volume
      of residual urine correlated poorly with subjective symptom, size of the
      prostate, maximum and average flow rate. On filling cystometry, although
      uninhibited detrusor contraction was much more frequently observed in patients
      with urge incontinence as compared with continent patients, there was no
      significant difference in other parameters between the two groups. Every
      parameter on cystometry did not correlate with nocturnal frequency. Postoperative
      persistence of urge incontinence did not correlate with the bladder volume at the
      first desire to void or at the maximum desire to void, an amplitude of
      uninhibited detrusor contractions, or bladder compliance. In some cases,
      evaluation of the intravesical pressure on voiding phase and uroflowmetry was
      diagnostic of apparent obstruction. CONCLUSIONS: In diagnosis of BPH,
      conventional UDS has limitation for certain and some caution showed be taken in
      interpretation of the data. However, since conventional UDS provides important
      and objective information on obstruction and detrusor function, which are
      independent of subjective symptom and prostate size, these should be necessary in
      diagnosis, determination of treatment options and evaluation of treatment
      outcomes in BPH.

PMID- 8997081
TI  - [A case of congenital ejaculatory duct obstruction].
AB  - We report a case of congenital ejaculatory duct obstruction treated successfully
      by transurethral incision. A 33-year-old man was referred for evaluation of
      primary infertility. His semen analysis showed volumes of 1.7 ml at average and
      azoospermia. Clinical examinations revealed right undescended testicle, absence
      of the left kidney and axial rotation of right kidney. Left vasogram showed
      dilated but intact seminal vesicle with no contrast material visible in the
      bladder. Following removal of right undescended testicle, transurethral incision
      of the left side of the prostatic urethral floor near the vermontanum was
      performed. Transurethral vesiculogram showed dilated but not cystic ejaculatory
      duct. Eight months postoperatively semen analysis showed a volume of 3.5 ml, a
      concentration of 61.3 x 10(6)/ml and motility rate of 51.8%. However, semen
      analysis 18 months postoperatively showed azoospermia again. After re
      transurethral incision, his sperm concentration increased to 15.2 x 10(6)/ml.
      However, his wife didn't become pregnant yet.

PMID- 8997082
TI  - [Forensic application of biochemical blood analysis--studies on CPK and LDH
      isozymes].
AB  - We analyzed CPK and LDH isozymes of the plasma of cadavers, which give indication
      of muscle damage in normal blood. The isozyme patterns in cadaveric plasma were
      different from those in normal plasma. The patterns were classified into five
      groups in CPK and four groups in LDH, respectively. We could not detect obvious
      correlation between the cause of death and each classified groups in CPK. In
      comparison with CPK, we detect the clear relation between the cause of death and
      isozyme patterns in LDH. All cases of LDH 1 and 5 predominant or LDH 1, 2 and 5
      predominant groups had myocardial infarction or other myocardial damage. So LDH
      isozyme pattern was informative for antemortem cardiac conditions of the cadaver
      and considered to be useful for conjecturing myocardial damage of the cadaver at
      least within 24 hours after death.

PMID- 8997083
TI  - [Examination of the degree of agreement among dental findings used for personal
      identification (report 5)--canonical correlation between dental findings on
      dental charts and those on radiographs].
AB  - Findings obtained from dental charts and from radiograph taken one year later for
      the same individuals were examined and classified according to different
      criteria. Similarities between the two sources investigated by the canonical
      correlation method. The results obtained were as follows: 1. The correlation
      coefficient and the squared multiple correlations (R2) were calculated.
      Consequently, high similarities were seen between the two sources for the
      mandibular anterior teeth [sequence: see text], maxillary incisor teeth
      [sequence: see text], mandibular and maxillary first premolar teeth [sequence:
      see text], and the corresponding teeth of the same jaws. 2. Three roots showed
      high elucidative values by the canonical correlation method. The first root was
      understood to be the mandibular incisor factor, the second the maxillary incisor
      factor, and the third the first premolar factor. This seemed to indicate, that
      the similarities between the two sources in these regions were very high. 3. A
      study of the similarities between the two sources was done based on the
      individual scores of canonical variable loadings calculated in this analysis.
      High similarities were seen at [sequence: see text] in category 1 (intact & C1)
      for chart findings and category 1'(intact, C1-C3 & resin filling) for
      radiographic findings: at [sequence: see text] in category 2 (C2-C4, inlay &
      filling of repair) for chart findings and category 3'(stump of tooth) for
      radiographic findings; and at [sequence: see text] in category 3 (complete crown,
      jacket crown & post crown) for chart findings and category 3'(stump of tooth) for
      radiographic findings. 4. The present results suggest that if proper case in
      taken, one set of information can serve as a substitute for the other. In
      personal identification, higher efficiency may be achieved if this is borne in
      mind.

PMID- 8997084
TI  - Identification of menstrual blood by the simultaneous determination of FDP-D
      dimer and myoglobin contents.
AB  - FDP-D dimer (D-D) and myoglobin concentrations in peripheral, menstrual and
      postmortem blood/bloodstains were determined. The mean plasma concentrations of D
      D in peripheral, menstrual and postmortem blood were 0.047, 102 and 220
      micrograms/ml and those of myoglobin were 0.028, 0.066 and 727 micrograms/ml
      respectively. The mean D-D concentration in menstrual bloodstains was about 200
      times higher than in peripheral bloodstains. The myoglobin contents in both
      bloodstains were similar. The mean myoglobin content in postmortem bloodstains
      was about 4000 times higher than in menstrual bloodstains. By the simultaneous
      determination of D-D and myoglobin contents, blood or bloodstains containing
      large amounts of D-D and only a small amount of myoglobin could be identified as
      menstrual blood.

PMID- 8997085
TI  - STR typing of buccal swabs for paternity testing with reference to Japanese
      population data on the D20S85, D14S118, and D14S543 loci.
AB  - To simplify short tandem repeat (STR) typing of genomic DNA, we used buccal cells
      instead of blood cells. Buccal swabs taken from paternity-test trios were washed
      with 1 ml of distilled water by centrifugation, and the pellets were suspended in
      20 microliters of distilled water. The suspensions were frozen at -80 degrees C
      and then thawed. Using a 1/5 volume of each suspension, we were able to type STRs
      at the TH01, D20S85, D14S118, and D14S543 loci by triplex PCR amplification of
      the first three markers and by simplex amplification of the other. In addition,
      we studied the polymorphisms at the D20S85, D14S118, and D14S543 loci in a
      Japanese population of 320 individuals. The four loci have a combined average
      exclusion power of 99.37%. In 24 cases of disputed paternity, the results of STR
      typing of the four loci agreed with those of conventional marker typing. In
      addition to being simple and rapid, STR typing of buccal swabs involves no
      painful procedure. It is therefore preferable for paternity tests on infants and
      small children.

PMID- 8997086
TI  - Comparison of heavy metal concentrations in human umbilical cord in 1980 and
      1990.
AB  - The well-known Minamata disease was caused by mercury; the Itai-Itai disease by
      cadmium; and lead poisoning by gasoline additives. Following our previous
      investigation on heavy metal concentrations in the umbilical cords in 1980, total
      mercury, cadmium and lead concentrations in the umbilical cords (from 20 males
      and 20 females) have been measured in 1990 for comparison in the present study.
      The changes in metal concentrations in 1980 and 1990 were: from 0.007 +/- 0.005
      microgram/g to 0.011 +/- 0.008 microgram/g for total mercury; from 0.019 +/-
      0.016 microgram/g to 0.006 +/- 0.005 microgram/g, from 0.151 +/- 0.123
      microgram/g to 0.046 +/- 0.038 microgram/g for lead. Total mercury accumulated in
      the umbilical cords increased to approximately 1.6-fold, while cadmium and lead
      decreased to approximately 1/3-fold during these 10 years.

PMID- 8997087
TI  - [An autopsy case of the Reye's syndrome].
AB  - A case of sudden unexpected natural death in a 6-year-old girl was reported. She
      was found in dead with vomiting on her bed in the morning on 24. December.
      Autopsy did not reveal any injuries and abnormalities on her appearance. Small
      amount of light yellowish mucus in her nose, trachea and bronchus was found.
      Brain was slightly edematous (1395 g in weight). Liver was 750 g in weight and
      focal yellowish lesions were observed on its cut surfaces. Microscopically fatty
      degeneration (granulous fatty deposits) was observed in hepatocytes.
      Immunohistochemical staining of mitochondria in heart showed no staining
      microscopically, and degeneration and breakdown of mitochondria were found
      electromicroscopically. From the results of autopsy and histopathological
      findings, her cause of death was diagnosed as the Reye's syndrome.

PMID- 8997088
TI  - STR typing in a deficiency case of disputed paternity.
AB  - In a case of disputed paternity where the alleged father was dead and the
      children and their mothers were available for testing, we analyzed 23
      conventional hemogenetic markers and six short tandem repeat loci. We deduced the
      possible types of the alleged father and calculated the probability of paternity.
      Conventional phenotypings did not provide conclusive proof of paternity. In
      contrast, typing of the short tandem repeat loci gave a combined probability of
      paternity of 0.9986, establishing paternity. The present study demonstrates the
      power of short tandem repeat typing as a tool for solving such a deficiency case.

PMID- 8997089
TI  - STR typing of plasma DNA in a deficiency case of disputed maternity against a
      patient dying in the hospital.
AB  - In this deficiency duo case, the plasma that had been left over after clinical
      diagnostic tests was the only blood sample available from the deceased alleged
      mother. Since her blood had been ABO grouped during hospitalization, we tested
      the plaintiff for the ABO system first. Then, to draw as much genetic information
      as possible from their plasma, we phenotyped 13 plasma protein systems and, three
      and a half years later, analyzed three short tandem repeat (STR) loci. The
      conventional phenotyping and STR genotyping gave probabilities of maternity of
      0.974 and 0.967, respectively, bringing the total probability to 0.999. The
      present study highlights the utility of plasma STR typing in case of need.

PMID- 8997090
TI  - [Postoperative swallowing function in tongue and oral floor cancer patients
      reconstructed with a recto-abdominal myocutaneous free flap after glossectomy-
      quantitative assessment of reconstructed tissue movement].
AB  - We examined the postoperative swallowing function of 12 tongue and oral floor
      cancer patients reconstructed with a recto-abdominal myocutaneous free flap after
      glossectomy. On the basis of the resection site, the present cases were
      classified into either anterior type or lateral type. Subjective evaluation of
      postoperative swallowing function was obtained from self-reports from patients.
      The movement of the reconstructed tissue was evaluated videofluorographically
      during swallowing, by tracking the movement of two small pellets temporarily
      attached to the anterior and central portions of the reconstructed tongue. The
      trajectory of the two pellets and the selected point of the hyoid bone were
      recorded together with the distance between the plate and the tongue dorsum, and
      between the posterior pharyngeal wall and the tongue base. Using a personal
      computer, a quantitative study of the video images was performed. The results
      were summarized as follows. 1) The movement pattern of the reconstructed tissue
      was generally saccadic rather than smooth. It was suggested that the swallowing
      pattern of the patients was different to that of normal controls. 2)
      Postoperative swallowing function was poorer in cases of the anterior type when
      compared to the lateral type. 3) In general, cases which showed relatively wide
      movement range appeared to achieve subjectively satisfactory swallowing function.

PMID- 8997091
TI  - [Cochlear morphological changes over time after the introduction of bacterial
      endotoxin into the middle ear].
AB  - Guinea pigs weighing 350 g each were used in this experiment. A small piece of
      Gelform containing 0.04 mg of E. coli derived endotoxin was set on the round
      window 24 hours after intraperitoneal injection of 0.02 mg endotoxin.
      Morphological changes in the cochlea were observed at 24 hours (previous report),
      48 hours, 72 hours and 7 days after the introduction of the endotoxin into the
      middle ear. As the results of the morphological changes of cochlea at 24 hours
      after the introduction of the endotoxin were reported in previous paper we
      present only an outline of these. Inflammatory cell infiltration and bleeding
      were observed in both endolymphatic and perilymphatic spaces. Inflammatory cells
      also infiltrated the stria vascularis, spiral ligament, spiral prominence and
      organ of Corti. Almost all of the inflammatory cells were neutrophils. Blood
      sludge was observed in all of the strial capillaries of the upper three turns.
      The hair cells were intact in every turn except for having small vacuoles.
      Intermediate cells and marginal cells of the stria vascularis were shrunken. At
      48 hours after the introduction of the endotoxin into the middle ear, the changes
      in the stria vascularis were almost the same as at 24 hours. However the
      infiltrated inflammatory cells changed from neutrophils to macrophages.
      Macrophages had phagocytosed many neutrophils. The hair cells had many large
      vacuoles. At 72 hours, the enlargement of the intercellular space in the stria
      vascularis disappeared and damage to the hair cells decreased although many
      macrophages were still observed. At 7 days, the cochlea was morphologically
      normal.

PMID- 8997092
TI  - [Long-term results of Feldmann's osteoplastic approach for chronic middle ear
      disease].
AB  - Between 1978 and 1981, Feldmann's osteopathic approach was often used to manage
      chronic middle ear disease. In this procedure, the superior and posterior segment
      of the ear canal wall was cut after complete mastoidectomy, removed temporarily
      and re-positioned in the previous position after handling the diseased focus in
      the tympanic isthmus area. Forty-one cases (24 cases of non-cholesteatomatous
      chronic otitis media and 17 cases of cholesteatoma) were followed and long-term
      results of this procedure were studied with regard to re-operative findings
      following this procedure. Among the 41 patients, 13 (31.7%) required revision
      surgery because of cholesteatoma formation, infection etc. Seven of these 13
      patients (53.8%) required revision surgery because of cholesteatoma formation
      after this procedure. None of these 7 cases appeared to involve residual
      cholesteatoma. The most important problem is that 3 of the 7 patients showing
      cholesteatoma formation had non-cholesteatomatous chronic otitis media before
      this procedure. In other words, the Feldmann's osteoplastic approach may
      iatrogenically induce cholesteatoma formation in non-cholesteatomatous chronic
      otitis media. The re-operative findings indicated that the re-positioned canal
      wall in this procedure may have small bony defects or bony erosion, inducing
      pocket formation through these defects to create a new cholesteatoma. Although
      recent literature concerning tympanoplasty recommends posterior canal wall
      reconstruction using cartilage, bone, ceramic material or bone-pate rather than
      the canal wall down method, careful follow-up should be continued with regard to
      pocket formation and/or cholesteatoma formation.

PMID- 8997094
TI  - [Otorhinolaryngological medical care by the general practitioners in rural
      areas].
AB  - In the present study, a survey of otorhinolaryngological medical care by the
      general practitioner, including the relationship between general practitioners
      and otorhinolaryngologists in rural areas was carried out. A questionnaire for
      otorhinolaryngological medical care by the general practitioners was sent to 326
      hospitals with less than 100 beds where non-otorhinolaryngological doctors who
      had graduated from Jichi Medical School were working. Of these hospitals 164
      (50.4%) responded. Most respondents said that they had about 3 or 4 patients with
      otorhinolaryngological disease per month. The distance between most hospitals and
      the nearest otorhinolaryngologists was within one hour by available
      transportation facilities. About 70% of the respondents were provided with simple
      otorhinolaryngological instruments, such as an aural speculum, a nasal speculum
      and a head mirror. The most frequent otorhinolaryngological diseases which they
      treated were vertigo, allergic rhinitis and upper respiratory infection including
      acute tonsillitis and pharyngolaryngitis. Only 10 to 20% of the general
      practitioners had otorhinolaryngological training. We found several problems in
      otorhinolaryngological medical care in rural areas. Patients with
      otorhinolaryngological disease seek otorhinolaryngological care at the nearest
      medical facility where general practitioners with inadequate
      otorhinolaryngological experience examine patients with inadequate
      otorhinolaryngological instruments. Therefore, a close relationship between
      general practitioners and otorhinolaryngologists should be developed and the
      quality of otorhinolaryngological medical care should be raised in rural areas.

PMID- 8997093
TI  - [Three-dimensional analysis of vestibulo-ocular reflexes--the relation between
      head position and eye movement].
AB  - Three-dimensional analysis of vestibulo-ocular reflexes, using a computerized eye
      movement analysis system, was carried out in 16 normal human subjects. We
      examined the relationship between head position and vestibulo-ocular reflexes.
      The purpose of this study was to clarify the relationship between the functional
      plane and the anatomical position of the semicircular canals. The subjects were
      stimulated by pendular rotation with their heads fixed between 40 degrees nose
      down and 50 degrees nose up in 10 degrees steps with respect to the orbitomeatal
      line and the lateral canal line. The gain in horizontal eye movement which
      results from the lateral canal, was the highest at 20 degrees nose down. On the
      other hand, the gains in vertical and torsional eye movement, which result from
      the vertical canals, were the lowest at 10 degrees nose up. The phase of vertical
      and torsional eye movement changed 180 degrees at 10 degrees nose up. These data
      indicate that the functional plane of the lateral canal almost coincided with the
      anatomical position. However, at this functional plane of the lateral canal, the
      influence of vertical canals was not the least. We suggest that this could be the
      reason why angles formed by the intersection of the lateral canal plane and the
      vertical canals were not 90 degrees. We could interpret this finding as showing
      that at the 10 degrees nose up position, the origin of eye movement alternated
      between the frontal and posterior canals.

PMID- 8997096
TI  - [Clinical features and prognosis of facial palsy and hearing loss in patients
      with Ramsay Hunt syndrome].
AB  - Clinical studies were performed on 325 patients with Ramsay Hunt syndrome who
      were treated in the Facial Nerve Clinic at Ehime University Hospital between 1976
      and 1995. The clinical manifestations of Ramsay Hunt syndrome were various. Three
      major symptoms, auricular vesicles, facial paralysis and vestibulo-cochlear
      dysfunction, were found in 57.6% of the patients although these symptoms did not
      always appear simultaneously. Auricular vesicles appeared before (19.3%), during
      (46.5%), or after (34.2%) the onset of facial paralysis. Hearing loss was
      observed subjectively in only 20% but objectively in 48.2% of the patients.
      Hearing loss appeared before (34.3%), during (34.3%), or after (31.3%) the onset
      of facial paralysis. Complete recovery from facial paralysis was achieved in
      52.4% of the patients. Good recovery of the facial nerve function was achieved in
      patients who had zoster vesicles or vestibulo-cochlear dysfunction preceding the
      development of facial paralysis. Complete recovery of hearing was also achieved
      in 45.4% of the patients, and the recovery was better in patients having light
      hearing loss, less than 35dB. The patients younger than 16 years old showed
      better recovery from both facial paralysis and hearing loss than the patients
      older than 60 years. Glossopharyngeal nerve or vagal nerve paralysis concomitant
      with facial paralysis was found in 8 (2.5%) patients. The outcome of
      glossopharyngeal nerve paralysis was good but that of the vagal nerve was poor.

PMID- 8997097
TI  - [Assessment of biological age and indices of aging].
AB  - People age at different rates. Accurate assessment of aging is indispensable for
      research in gerontology and geriatrics. Biological age can be estimated from age
      related changes in physiological and physical functions. Disease, physical
      activity, and life-style have been shown to affect aging. Biological age was
      estimated by multiple regression. We studied how external appearances, diet, job
      status, smoking and alcohol consumption were related to aging. The subjects were
      2,385 people of both sexes whose ranged from 15 to 87 years. Aging estimated by
      external appearance strongly correlated with changes in physiological functions
      and in physical strength. Diet was also found to be significantly related to
      aging. Biological age was significantly lower than calendar age in subjects with
      managerial jobs in non-smokers, and in those who drank a moderate amount of
      alcohol. These results show that biological age can be useful in aging research.

PMID- 8997095
TI  - [Characteristics of auditory brainstem response in presbyacusis--compared with
      the results of pure tone, speech or binaural audiometry].
AB  - The relationships between the auditory brainstem response (ABR) latencies and the
      results of three phychophysical measurements-pure tone audiometry, speech
      discrimination test and directional hearing test-were investigated in 58 subjects
      with presbyacusis. ABR latencies in presbyacusis patients were also compared with
      those in young adults with normal hearing or cochlear hearing loss. The results
      were as follows: There was a significant correlation between the average
      thresholds of pure tone audiometry and latencies of ABR waves I, III, V and/or
      interpeak latencies of waves I-III and I-V. There was a significant correlation
      between the scores of the speech discrimination test and latencies of waves I,
      III and V. There was also a significant correlation between the value of the
      directional hearing test and only interpeak latency of waves I-III. It was found
      that the I-III peak interval was prolonged in the ABR of presbyacusis, and that
      the results of pure tone audiometry and directional hearing tests were rather
      well correlated with the prolonged I-III peak interval.

PMID- 8997098
TI  - [A neuropsychological index of aging--data from 9000 elderly people].
AB  - Cerebral functions degenerate at different rates in different people, and it is
      often necessary to measure these functions accurately: for example, to assess the
      condition of patients with senile dementia. We used newly developed tests and
      measured the functions of 9000 elderly people. The Kana Pick-out Test was one of
      the test used, in which the examinee is asked to circle only the 5 vowel-kanas as
      many as possible within two minutes and also to retain the meaning of the story.
      Functions of the prefrontal lobe was found to be similar among people of similar
      age. It was also found to be linearly and inversely associated with age. With the
      results of these tests, abnormal declines in function were relatively easy to
      detect.

PMID- 8997099
TI  - [Variability in gait among patients with Alzheimer-type dementia].
AB  - We studied age-related changes in gait and equilibrium in healthy subjects and
      patients with Alzheimer-type dementia. We also studied the relation between gait
      and falling in institutionalized patients with Alzheimer-type dementia. Among
      healthy subjects, higher age was associated with greater postural sway, slower
      walking speed, and shorter stride length, but age was not associated with stride
      length variability. In patients with mild Alzheimer-type dementia, both postural
      sway and stride length-variability were greater than in healthy subjects. Among
      patients who had fallen, stride length-variability was high. Variability in gait
      may be useful in distinguishing normal age-related decreases in gait from those
      associated with disease.

PMID- 8997100
TI  - [Evaluation and index of age-related change in circulatory function].

PMID- 8997101
TI  - [Effect of aging on respiratory system].

PMID- 8997102
TI  - [Hypersensitivity in the pupil dilation response to a cholinergic antagonist in
      patients with Alzheimer's disease and Down's syndrome].
AB  - In 1994, Scinto et al. reported hypersensitivity in the pupil-dilation response
      to topical application of a cholinergic antagonist, tropicamide, in patients with
      Alzheimer-type dementia. Similar tests on Japanese subjects showed significant
      differences in pupil response between subjects with Alzheimer-type dementia
      (under age 70 years) and age-matched controls. The present study included 24
      patients with early-onset Alzheimer-type dementia, 29 patients with late-onset
      Alzheimer-type dementia, 15 healthy controls (all spouse of patients with
      Alzheimer-type dementia), 9 patients with vascular dementia and 5 patients with
      Down's syndrome. After adapting to semi-darkness (10 lux), a solution of
      tropicamide (Midrin-P, Santen Co, Ltd) was instilled into the right eye. Pupil
      diameters were measured every 5 to 10 min, and the maximum pupil diameter for
      each eye was used in the data analysis. The solution was diluted until the
      tropicamide concentration reached 0.01%. Pupil diameters were measured, and
      differences between baseline and maximum pupil diameter were computed. Among 18
      patients with early-onset Alzheimer-type dementia (mean age 63.9 years) the
      pupils dilated by 1.12 +/- 0.52 mm (mean +/- SD) as compared with 0.20 +/- 0.75
      mm in 7 age-matched controls (mean age 57.8 years); this difference was
      significant (T-test, p < 0.05). Correlations between the degrees of pupillary
      dilation and the scores on the revised version of Hasegawa's Dementia Scale were
      not significant. These data suggest that in subjects under 70 years of age, the
      diagnostic methods described by Scinto et al. can be used to distinguish those
      with Alzheimer-type dementia from those without dementia, but those methods may
      not be effective in subjects over 70 years of age.

PMID- 8997103
TI  - [Risk factors related to the wall thickness of the common carotid artery in
      elderly patients].
AB  - We used ultrasonography to evaluate atherosclerotic lesions in the common carotid
      arteries of 147 inpatients (82 men, 65 women; mean age, 72.2 years). We sought to
      determine the relation between these lesions and various risk factors for
      atherosclerosis, as well as the utility of ultrasonography in quantitative
      evaluation of atherosclerotic disease. A 7.5 MHz transducer was used and
      atherosclerotic lesions were evaluated on the basis of the thickness of their
      intimal-medial complex, which we term wall thickness. The relations between these
      measurements and age, sex, blood pressure, smoking history, lipid metabolism,
      diabetes mellitus, and atherosclerotic disease were studied. Wall thickness of
      the common carotid arteries correlated with age (men: r = 0.45; women: r = 0.38).
      Brinkman Index (r = 0.25), systolic blood pressure (r = 0.44), diastolic pressure
      (r = 0.18), and high-density lipoprotein cholesterol (HDL-C, r = -0.23). Multiple
      regression analysis with these risk factors as explanatory variables showed that
      age, Brinkman Index, systolic blood pressure, HDL-C, and diabetes mellitus
      contributed significantly to increased wall thickness. Wall thickness was
      significantly greater in patients with atherosclerotic disease such as cerebral
      infarction and ischemic heart diseases. These findings indicate that appropriate
      treatment for multiple atherosclerotic risk factors may be necessarily in the
      elderly.

PMID- 8997104
TI  - [Effect of measuring bone mineral density on calcium intake].
AB  - The diet in Japan has improved, but calcium intake has not increased for the past
      ten years, and it remains insufficient. To prevent osteoporosis, instruction in
      nutrition is directed at increasing calcium intake. We studied the effect of
      measuring bone mineral density on calcium intake in people receiving nutrition
      education. Intake of other nutrients was also measured. The subjects were 87
      healthy women living in an agricultural region (Yamanashi Prefecture). They were
      members of a group formed to improve the diet of people in their area. For three
      days in October 1992 and in August 1994 food-weight records were obtained. A
      total of 76 of the 87 women chose to have their bone mineral density measured.
      The measurements before the first nutrition assessment in 1992. The intake of
      almost all nutrients tended to be greater in 1994 than in 1992. Calcium intake
      exceeded the minimum daily requirement (600mg). Calcium intake increased between
      1992 and 1994 only in the subjects whose bone mineral density had been measured.
      Calcium intake decreased in the other subjects. Therefore, nutrition education
      programs aimed at preventing osteoporosis may be more effective if bone mineral
      density is measured. In addition, an appropriate balance of other nutrients can
      be maintained as the intake of calcium is increased.

PMID- 8997105
TI  - [Changes in erythrocyte structure and in platelets in elderly patients with
      disseminated intravascular coagulation].
AB  - We measured the platelet distribution width, the mean platelet volume, the volume
      percentage of platelets, and the platelet-to-large-cell ratio in 15 elderly
      patients with disseminated intravascular coagulation (DIC). Peripheral venous
      blood mixed with ehtylenediaminetetraacetic acid was analyzed with a Sysmex E
      4000 analyzer. The underlying diseases were sepsis, pneumonia, pyelonephritis,
      and other inflammatory diseases. The mean duration of survival from the onset of
      DIC was 16.9 +/- 23.9 days. The distribution of red cell sizes before the onset
      of DIC did not differ significantly from that in patients without DIC, but
      fragmentation of erythrocytes on blood films was more common in the early stage
      of DIC (p < 0.01). Before the onset of DIC, the two groups did not differ
      significantly in the frequency of giant platelets on blood smears. At the onset
      of DIC, the platelet distribution width, the mean platelet volume, and the
      platelet-to-large-cell ratio were significantly higher than in patients without
      DIC. The concentration of glutamic-oxaloacetic transaminase and those of other
      serum enzymes did not change significantly, but the serum creatinine
      concentration and the blood urea nitrogen level increased as the platelet-to
      large-cell ratio increased. No significant relation was evident between the
      levels of serum C-reactive protein and creatinine, between the platelet-to-large
      cell ratio and the mean volume of red blood cells, or between the platelet-to
      large-cell ratio and the distribution of red cell sizes. These data suggest that
      studies of platelets are more useful in the diagnosis of DIC at early stages of
      impaired organ function than are other indicators of inflammation such as the
      level of C-reactive protein.

PMID- 8997106
TI  - [Changes in serum Lp(a) and apo(a)phenotype in patients with acute cerebral
      stroke].
AB  - 33 patients with acute cerebral stroke (21 men and 12 women, averaged age 69.9 +/
      11.2 years) were examined for fluctuations in the level of serum Lp(a) 3, 7, 14,
      and 28 days after the onset of symptoms. The Lp(a) level was higher (p < 0.05, p
      < 0.001) on days 7 and 14 than on the day of onset. Higher values were associated
      with poorer outcomes and with larger abnormal densities on brain CT scans. In 33
      of these patients, the apo(a)phenotype was determined. Diluted serum was
      electrophoresed with SDS-containing gel as a carrier, then transcribed on a
      nitrocellulose membrane, stained by Western blotting and then sensitizing
      stained. The results were evaluated by the method of Utermann et al. Outcome was
      significantly poorer in patients with a double-band apo(a)phenotype than in those
      with a single-band (p < 0.05). Those with a double-band had significantly higher
      mean value of Lp(a), except on the day of onset, than did those with a single
      band. Patients with large degrees of electrophoresis had significantly higher
      values of Lp(a) than did those with small degrees. These data suggest that serial
      measurement of Lp(a) can be of some value in predicting the outcome in patients
      with cerebral stroke. Determination of apo(a) phenotype may also be useful in the
      prevention and prognosis of cerebral stroke, especially when it is caused by
      cerebral infarction.

PMID- 8997107
TI  - [Surgical treatment of secondary chronic colonic pseudo-obstruction].
AB  - A 74-year-old woman was admitted to the hospital because of constipation and
      marked abdominal distension. She had become to be bedridden after cerebral
      infarction 10 years previously, and was tabescent due to vomiting. A left
      hemicolectomy and colostomy were performed because conservative therapy seemed to
      be ineffective. The postoperative course was good and her nutritional status
      improved.

PMID- 8997108
TI  - [Acute myocardial infarction with idiopathic thrombocytopenic purpura in an
      elderly patient].
AB  - A 71-year-old woman complained of gingival bleeding and epistaxis, and was given
      a diagnosis of idiopathic thrombocytopenic purpura. She was successfully treated
      with orally administered prednisolone and azathioprine. She experienced a relapse
      when she was 77 years old, and immunosuppressive therapy was not effective.
      Platelet transfusion was performed. She died because of massive gastrointestinal
      bleeding. An infarct was found in the left anterior part of the myocardium at
      autopsy. Disseminated intravascular coagulation was not detected on pathological
      investigation. Abnormal platelet aggregation may be important in the pathogenesis
      of thrombotic disease in thrombocytopenia.

PMID- 8997109
TI  - The sun breaks through the clouds: a bright future for physiology. A report from
      the Long-Range Planning Committee.

PMID- 8997110
TI  - Psychiatry in medical practice. Implications for the education of primary care
      physicians in the era of managed care: Part 2.
AB  - In Part 1 of this 2-part series, the epidemiology of psychiatric disorders in
      primary care settings was reviewed as well as evidence that indicates that these
      conditions often go underrecognized and undertreated by primary care physicians.
      Educational studies to improve the psychiatric skills of primary care physicians
      were also reviewed. In Part 2 of this series, a core curriculum for primary care
      physicians in the diagnosis and treatment of psychiatric disorders that
      emphasizes competency-based learning is presented. Recommendations for the
      development and implementation of these competency-based training modules are
      offered in the conclusion.

PMID- 8997111
TI  - Psychological distress among adult patients being evaluated for bone marrow
      transplantation.
AB  - A sample of 437 patients being evaluated for bone marrow transplantation (BMT)
      completed interviews and questionnaires to assess their psychosocial adjustment.
      Nearly a third of the patients (31%) showed some degree of depression on the
      Center for Epidemiologic Studies Depression Scale. Scores on the Profile of Mood
      States Scale also indicated that these BMT candidates were experiencing a high
      level of psychological distress. This distress was found to be predicted by low
      scores on the Self-Rated Karnofsky Performance Scale and on scales measuring
      mastery and dispositional optimism. The value of assessing the levels of
      psychological distress and psychosocial resources of patients being evaluated for
      BMT and for providing necessary psychiatric interventions are discussed.

PMID- 8997112
TI  - Relationship of alexithymia and poor social support to ulcerative changes on
      gastrofiberscopy.
AB  - The effects of psychosocial factors on peptic ulceration and/or erosions were
      examined in a sample of 189 volunteers. Analysis of variance found that the
      severity of gastrofiberscopic findings was related to two psychosocial factors
      poor social support and degree of alexithymia- and that both psychosocial factors
      were significantly correlated with one another. Analysis of covariance indicated
      that gastrofiberscopic findings remained significantly related to poor social
      support when alexithymia was controlled for. These findings suggest that in both
      healthy persons, and in persons with alexithymia, peptic ulceration or erosions
      tend to manifest when social support is low. Poor social support and alexithymia
      may be an especially high-risk combination for the development of peptic
      ulceration and/or erosions.

PMID- 8997113
TI  - Denying the dying. Advance directives and dialysis discontinuation.
AB  - A structured interview was administered to a sample of patients on maintenance
      dialysis and their attending physicians to obtain information on the
      documentation of their end-of-life treatment preferences. The majority of the
      patients reported never having considered stopping dialysis, or having discussed
      with their nephrologist or family the circumstances in which treatment should be
      discontinued. Only 7 patients (6%) had completed an advance directive; these
      patients were all men (P = 0.01) and tended to be better educated (P = 0.02).
      Only one of the nine physicians had completed an advance directive. In most
      cases, the dialysis patients and their treatment team staff were preoccupied with
      the struggles of daily life and had avoided or denied considerations of terminal
      illness and death. The literature on denial, medical illness, and dying is also
      reviewed as it relates to dialysis patients, end-of-life treatment, and terminal
      care.

PMID- 8997114
TI  - Transfer of psychiatric inpatients to a general hospital due to adverse drug
      reactions.
AB  - The authors review their experience with transfers of hospitalized psychiatric
      inpatients to general hospitals because of adverse drug reactions (ADRs). A total
      of 29 medical transfers related to ADRs were found in a review of 10,994
      psychiatric inpatient admissions that occurred in a 30-month period between 1990
      and 1993 (0.264%). Most cases involved neurological syndromes (76%), particularly
      delirium (31%). Low-potency antipsychotic agents were most frequently implicated
      (31%). Most ADRs were of moderate severity, but 8 cases required medical
      hospitalization (0.07% incidence). These findings indicate that ADRs leading to
      transfer of hospitalized psychiatric patients to a general medical facility were
      infrequent (< 0.3% of psychiatric admissions) and rarely led to medical
      hospitalization (< 0.1%).

PMID- 8997115
TI  - The timing of psychiatric consultation requests. Utilization, liaison, and
      diagnostic considerations.
AB  - Psychiatric consultation timing results from the interaction of multiple systems.
      This study examines the key clinical and systems variables and the effect of
      consultation timing on subsequent length of hospital stay. One hundred and forty
      five consecutive psychiatric consultations at a New York City teaching hospital
      were assessed by demographic criteria, medical and psychiatric diagnoses, reasons
      for consultation, and the timing of the consultation with respect to the academic
      year. Twenty-five percent of the consultations occurred within the first 48 hours
      after admission and 32% occurred between Days 2 and 5. Consultations for
      schizophrenia patients were called earlier (P < 0.02) than those for patients
      with other diagnoses, and those for patients with the acquired immunodeficiency
      syndrome were called later (P < 0.04). Earlier consultations were associated with
      a shorter time to discharge (P < 0.002).

PMID- 8997116
TI  - The role of psychological variables in a group of melanoma patients. An Israeli
      sample.
AB  - This study examined whether there is a difference in the psychological distress
      and/or coping modes of patients with early localized malignant melanoma. The
      authors compared the patients diagnosed at stages IA and B of the disease with
      those diagnosed at stages IIA and B. The population consisted of 100 melanoma
      patients who agreed to take part in a study of adjustment to chronic disease. The
      patients were individually interviewed at home and completed six self-reports.
      Three of the reports assessed psychological outcome, two assessed coping, and one
      assessed support systems. No substantial differences were found between the
      patients treated at stages I and II on any of the psychological measures, despite
      the fact that those with greatest thickness and depth (stage IIB) are at higher
      risk of recurrence. The women showed greater distress than the men, confirming
      earlier observations made in patients with colon cancer.

PMID- 8997117
TI  - Impaired body image of young female survivors of childhood leukemia.
AB  - The purpose of this study was to assess the body image of young female survivors
      of leukemia. Young female survivors of leukemia (n = 42) were compared with
      healthy age-matched control subjects (n = 69). The study included a
      semistructured face-to-face interview and a psychological test. The data were
      separated into three distinct evaluations of each subject's body image: 1) the
      subject's self-assessment, 2) evaluation by a psychiatrist, and 3) the Rorschach
      test. The body images of the survivors were inferior to those of the control
      subjects in all three evaluations (P < 0.001). The preceding leukemia was
      assessed still as extremely threatening in 26% of the survivors.

PMID- 8997118
TI  - Irritable bowel syndrome and dysthymia. Is there a relationship?
AB  - Irritable bowel syndrome (IBS) has been reported in 10% to 22% of adults. The
      authors compared patients seeking treatment for dysthymia (N = 59) in an
      outpatient setting to an age- and sex-matched comparison group of patients (N =
      54) seeking treatment in a general physician's office for other medical
      illnesses. The comparison group did not have any Axis I disorders. IBS was
      diagnosed by using the criteria established by Drossman and colleagues. Of the
      patients screened, 59.32% of the patients with dysthymia met criteria for IBS in
      contrast to 1.85% of the comparison group (P < 0.000005). IBS is extremely
      prevalent in patients seeking treatment for dysthymia and is often undiagnosed
      and untreated.

PMID- 8997119
TI  - Challenges and opportunities for consultation-liaison psychiatry in the managed
      care environment.
AB  - While the evolving managed care revolution is dramatically changing the clinical,
      educational, and economic systems in which consultation-liaison (C-L)
      psychiatrists must operate, this revolution also present several important
      opportunities for those in C-L psychiatry. The authors, who are academic
      department chairs and formerly directed C-L divisions, discuss C-L psychiatry's
      potential involvement and suggest approaches to effectively address key aspects
      of these changes.

PMID- 8997120
TI  - Factitious quadriplegia. A rare new case and literature review.

PMID- 8997121
TI  - Severe sexual abuse and its relationship to the etiology of chronic pelvic pain
      in women.

PMID- 8997122
TI  - [Platelet substitutes--development and possible clinical applications].

PMID- 8997123
TI  - [Bone marrow transplantation versus maintenance chemotherapy for adult acute
      leukemia in first remission].
AB  - We compared the outcome of bone marrow transplantation (BMT) with that of
      maintenance chemotherapy for adults with acute leukemia who achieved first
      remission in Japanese Red Cross Nagoya First Hospital. From 1976 to 1993, 17
      patients with acute myelogenous leukemia (AML) and 10 patients with acute
      lymphoblastic leukemia (ALL) received allogeneic BMT from HLA genotypically
      identical siblings in first remission, 4 patients with ALL undertook purged
      autologous BMT using monoclonal antibody and complement, and 55 patients with AML
      and 27 patients with ALL were treated with maintenance chemotherapy. The
      estimated 6-year disease free survival (DFS) of AML patients was significantly
      higher in the BMT group than in the chemotherapy group (77.3% vs 42.6%; p <
      0.01). For ALL patients, the estimated 6-year DFS was 72.5% in the allo-BMT group
      and 100% for the auto-BMT group, but no patient was disease free more than 2
      years in the chemotherapy group (p < 0.0001). We conclude that BMT after several
      courses of consolidation chemotherapy is the optimal treatment of choice in
      patients with AML and ALL in first remission. A prospective study is needed to
      confirm the efficacy of BMT after intensive consolidation chemotherapy.

PMID- 8997124
TI  - [Cord blood stem cell transplantation for a patient with acute myelogenous
      leukemia (M1)].
AB  - A five-year-old boy with acute myelogenous leukemia in relapse was treated by HLA
      matched cord blood stem cell transplantation. The patient was preconditioned with
      16 mg/kg of busulfan, 15 mg/kg of thiotepa and 90 mg/kg of cyclophosphamide and
      2.45 x 10(7)/kg of cord blood mononuclear cells were infused to the patient on
      October 19th 1995 without the prophylaxis of graft-versus-host disease (GVHD).
      From the fifth day following the transplant, rG-CSF was administered at a dose of
      300 micrograms/m2/day. Hematopoietic recovery was obtained as following; WBC over
      1000/microliters was on +18 day, neutrophil over 500/microliters was on +20 day,
      reticulocyte over 20/1000 was on +28 day and platelet over 50 x 10(2) microliters
      was on +91 day. Engraftment was confirmed by DNA restriction fragment length
      polymorphism (VNTR) on +28 day. In spite of absence of prophylaxis of GVHD, the
      patient did not develop any signs of GVHD, and leukemia relapsed on +105 day. The
      patient died of leukemia relapse on +251 day. This is the first case of cord
      blood stem cell transplantation in Japan.

PMID- 8997125
TI  - [CD2 and CD8 expression in acute promyelocytic leukemia].
AB  - A 34-year-old man was admitted to our hospital for a headache in March, 1995. The
      patient's hemoglobin was 7.5 g/dl, platelet count was 1.8 x 10(4)/microliter and
      white blood cell (WBC) count was 12,400/microliters with 99% myeloblasts.
      Myeloblasts were agranular or hypogranular but electron microscopy revealed
      microgranules in cytoplasm, and a few faggots were observed. The bone marrow was
      hyperplastic due to myeloblasts and chromosomal abnormality was recognized: 46,
      XY, t(15; 17) (q22; q12). PML-RAR alpha with intron 3 breakpoint of the PML
      locus, and rearrangements of the T-cell receptor beta and gamma genes were
      detected. These cells were positive for CD2 (63%), CD8 (47%), CD13 (87%) and CD33
      (99%). Microgranular variant type of acute promyelocytic leukemia (APL) was
      diagnosed. Disseminated intravascular coagulation (DIC) was also present. The
      patient was treated with enocitabine, daunorubicin, 6-mercaptopurine, dalteparin
      sodium, anti-thrombin III concentrates and gabexate mesilate with prophylactic
      frozen transfusions of fresh plasma and platelet transfusions for 5 days, but WBC
      count did not decrease and DIC did not improve. The patient died of cerebral
      hemorrhage 7 days after diagnosis of APL. APL with CD8 expression has never been
      reported. We suggest that therapy should be modified in this type of APL and
      conclusions concerning the most appropriate therapeutic strategy will depend on
      the results of treatment of similar cases in the future.

PMID- 8997126
TI  - [Nephrotic syndrome related to chronic graft versus host disease after allogeneic
      bone marrow transplantation in a patient with malignant lymphoma].
AB  - A 13-yr-old boy was diagnosed as T cell lymphoma. After the second remission, he
      underwent BMT from an HLA-identical, MLC negative sibling donor. After BMT, he
      developed grade II acute GVHD. GVHD was improved by pulsed steroid therapy using
      prednisolone. About 12 months after BMT, he developed bronchiolitis obliterans,
      sicca syndrome, and leukoderma, which were related to chronic GVHD. Pulsed
      steroid therapy was carried out twice, and his condition improved. Twenty-seven
      months after BMT, he developed nephrotic syndrome. A renal biopsy was performed,
      and the diagnosis was histologically membranous nephropathy and focal glomerular
      sclerosis. The response to steroids was not satisfactory. After 5 weeks,
      dipyridamole was added, but proteinuria persisted. Proteinuria disappeared 8
      weeks after the addition of cyclosporine. The second biopsy after 5 months of
      treatment revealed an improvement in the renal lesions. The patient showed a low
      T4 to T8 ratio of T-lymphocytes at the onset of nephrotic syndrome. However after
      treatment with cyclosporine, the ratio gradually increased. These findings
      suggested the nephrotic syndrome in this patient was related to renal involvement
      in the course of chronic GVHD.

PMID- 8997127
TI  - [A case of hemolysis induced by lansoprazole].
AB  - Hemolytic anemia and possible aplastic crisis with symptoms including jaundice,
      general fatigue and dark urine developed in a man being treated only by
      lansoprazole. Five days later, he was treated with antibiotics. The next day, he
      was admitted to our hospital because of jaundice. On admission, the hemoglobin
      was 14.0 g/dl, reticulocyte count 8/1000, platelets 79 x 10(9)/l and total
      bilirubin 12.4 mg/dl (indirect bilirubin 9.5 mg/dl). The above medications were
      discontinued. The direct Coombs antiglobulin test was positive. Examination of
      the complement revealed a C3 fiter at the upper limit of normal and an increased
      C4 and CH50. Three days after admission, he had a severe anemia. The hemoglobin
      was 3.3 g/DL. We thought it possible that aplastic crisis had followed the
      hemolytic anemia induced by lansoprazole. He was treated with blood transfusions
      and corticosteroids. He recovered from anemia within three weeks. Exhaustive
      studies to identify the cause of the hemolytic anemia were undertaken with
      negative results. We detected IgG antibody to lansoprazole. We believe that the
      hemolytic anemia was induced by lansoprazole.

PMID- 8997129
TI  - [Mantle cell lymphoma associated with hyper-IgE syndrome].
AB  - A 69-year-old woman was admitted with generalized lymph node swelling and huge
      splenomegaly. CD5(+), Sm-IgM (+) and SmIgD (+) lymphocytes were increased in
      lymph nodes, spleen and bone marrow, and she was diagnosed as having mantle cell
      lymphoma. A diagnosis of hyper-IgE syndrome was also made, because IgE was
      markedly increased (174,780 u/ml) and chronic dermatitis, which was often
      complicated with infection, occurred repeatedly on her extremities. In this case,
      interleukin-4 was considered to be one of the factors involved in the hyper-IgE
      syndrome, because increased IgG1 and reduced IgG2 were observed. Immunological
      abnormality associated with the hyper-IgE syndrome seemed to contribute to the
      development malignant lymphoma in this case.

PMID- 8997128
TI  - [Successful treatment with combination of all-trans retinoic acid (ATRA) and rhG
      CSF a relapsed acute promyelocytic leukemia with umbilical tumor].
AB  - A 48-year-old female was admitted to our hospital because of pancytopenia and
      pneumonia in February, 1993. The increase of abnormal promyelocytes with t (15;
      17) and PML-RAR mRNA was detected in bone marrow aspirate and a diagnosis of
      acute promyelocytic leukemia was made. She obtained complete remission after the
      administration of all-trans retinoic acid (ATRA) and following chemotherapy. Then
      she received peripheral blood stem cell transplantation in September, 1993.
      However she noticed a umbilical tumor in June, 1995. Abnormal promyelocytes were
      demonstrated not only in bone marrow aspirate but also in the umbilical tumor.
      Because of the poor response to ATRA and development of fever, a side effect of
      ATRA, G-CSF and prednisolone were administrated together with ATRA. After the
      combined therapy, umbilical tumor disappeared and she obtained complete remission
      again. These findings suggest that combined therapy of ATRA and G-CSF is
      effective to the low responder to ATRA and that combined use of ATRA and
      prednisolone reduces the side effect of ATRA without diminishing the favorable
      effect on differentiation.

PMID- 8997130
TI  - [Polycythemia vera progressing to acute lymphoblastic leukemia after 13 years].
AB  - A 54-year-old woman with leukocytosis, was referred to our clinic in February
      1982. Based on findings of pancytosis, high NAP score, high serum vitamin B12,
      increase in total red cell volume and splenomegaly, she was diagnosed as having
      polycythemia vera (PV). Since then, she has been treated with pipobroman,
      hydroxycarbamide and phlebotomy. Leukocytosis with increase in blastic cells and
      thrombocytopenia was noted in August 1995, and she was admitted to our hospital.
      Since the blastic cells were CD10(+)19(+)20(+), she was diagnosed as having acute
      lymphoblastic leukemia and treated with vincristine and prednisolone, resulting
      in remission. This case suggests that PV is a disease of multipotent stem cells
      including those with a lymphoid lineage.

PMID- 8997131
TI  - [Childhood acute promyelocytic leukemia treated with all-trans retinoic acid].
AB  - We treated two children with acute promyelocytic leukemia (APL) in whom complete
      remission was successfully induced by oral administration of all-trans retinoic
      acid (ATRA). We followed these patients with conventional chemotherapy. The first
      patient has remained in continuous complete remission. However, the other patient
      relapsed during the maintenance therapy and died of progressive disease in spite
      of a second treatment with ATRA and chemotherapy. From a clinical point of view,
      the latter case had a hyperleukocytosis on admission. Also morphologically
      speaking, this patient had a different M3 variant than the first case. There are
      two major isoforms of PML/RAR alpha transcripts, so called short and long type
      transcripts, according to the breakpoints in the PML genes. In the first case the
      "long type' isoform was detected by reverse transcriptase polymerase chain
      reaction (RT/PCR) amplification. On the other hand the "short type' isoform was
      observed in the latter case. Also the second case became PCR positive at relapse,
      although the detectable isoform was negative during remission. The "short type'
      isoform may be related to the poor prognosis and RT/PCR analyses may be a
      powerful to detect early relapse.

PMID- 8997132
TI  - [An unusual case of multiple myeloma diagnosed by a noticeable decrease in the
      serum M-component level].
AB  - The author has recently observed an unusual case of multiple myeloma, which was
      diagnosed by a noticeable decrease in the serum monoclonal IgG (kappa) level in
      close association with Bence Jones escape. [Case Report] In June 1986, a 61-year
      old woman was noticed to have monoclonal gammopathy of undetermined significance
      (MGUS) at a local hospital. Bence Jones escape was found in association with a
      decrease in the serum M-component level in April 1991, when a diagnosis of
      indolent multiple myeloma was made. In April 1993, the daily amount of Bence
      Jones proteins excreted in the urine was 1 g. Examination of bone marrow aspirate
      demonstrated immature plasma cells in clusters. The patient was diagnosed of
      having overt multiple myeloma. The double immunofluorescence studies on the bone
      marrow plasma cells were performed. Only 40 percent of cells producing kappa
      light chains were found to be positive for gamma heavy chains, while all of gamma
      heavy chain-positive cells contained kappa light chains. kappa light chain
      positive cells were stained neither with anti-alpha, nor with anti-mu. From the
      above-mentioned data, the proportion was about two cells producing IgG (kappa) to
      three cells producing kappa light chain alone. Thus, myeloma cells contained two
      morphologically identical but immunologically diverse subpopulations.
      Conceivably, the subclone producing kappa light chain alone could be derived from
      the original clone producing monoclonal IgG (kappa). Bence Jones escape of this
      type has not hitherto been described.

PMID- 8997133
TI  - [Sezary syndrome associated with small intestinal amyloidosis].
AB  - A 68-year-old female diagnosed as having Sezary syndrome because of generalized
      erythroderma and increased lymphocytes with convoluted nuclei in 1988 was treated
      with steroids. However she did not respond to therapy and died due to pneumonia
      and aggravation of Sezary syndrome in September, 1994. Dyspeptic diarrhea was
      observed for two months before she died. Autopsy revealed local deposition of
      amyloid A protein in the mucosa of the small intestine, which might have been the
      cause of dyspeptic diarrhea. This was a rare case which Sezary syndrome
      accompanied by localized amyloidosis.

PMID- 8997134
TI  - [Erythropoietin improved anemia in a case of multicentric Castleman's disease].
AB  - Severe anemia A 37 year-old male with therapy resistant multicentric Castleman's
      disease (MCD) anemia was treated by subcutaneous injection of erythropoietin.
      Although immunoglobulin and CRP concentration increased, anemia obviously
      improved with hemoglobin levels increasing from 4.8 g/dl to 8.5 g/dl without any
      side effects. Colony assay revealed that the bone marrow mononuclear cells
      responded to erythropoietin in a dose dependent manner. The mechanism of anemia
      of MCD is not clearly understood, and treatment is sometimes very difficult.
      There is no other previous report concerning erythropoietin as a treatment for
      anemia in MCD.

PMID- 8997136
TI  - [Axial (neck and trunk) rigidity in Parkinson's disease, striatonigral
      degeneration and progressive supranuclear palsy].
AB  - Our previous study showed that the alternating knee tilt test in supine position
      is a useful method to assess the trunk rigidity. We investigated the progression
      of axial (neck and trunk) rigidity in Parkinson's disease (PD), striatonigral
      degeneration (SND), and progressive supranuclear palsy (PSP) by using this
      method. We assessed rigidity on a scale of 0 (absent) to 3 (severe) on five parts
      of the body: neck, trunk, wrist, elbow and knee in 57 patients with PD, 13
      patients with SND and 18 patients with PSP. In PD patients, the degree of neck
      and trunk rigidity correlated well with the duration of disease and the staging
      scale. There was neck rigidity in 27% of PD patients with unilateral involvement
      of the limbs, but the trunk tonus was normal in them. There was rigidity in the
      neck and trunk of all PD patients with bilateral involvement of the limbs. When
      the limb rigidity was predominant on one side, the trunk rigidity was predominant
      on the opposite side. In SND patients, the degree of neck and trunk rigidity
      roughly correlated with the duration of disease and the staging scale. In SND
      patients with unilateral involvement of the limbs, tonus of the neck and trunk
      was normal. In SND patients with bilateral involvement of limbs, there was
      rigidity in both the neck and the trunk. In PSP patients, the degree of neck
      rigidity correlated well with the duration of disease and the staging scale, but
      the degree of rigidity in the trunk and limb remained relatively mild even at the
      advanced stage. Accordingly, in PSP patients there was a dissociation of the
      degree of neck rigidity from that of trunk and limb rigidity. In conclusion, the
      assessment of axial (neck and trunk) rigidity may be useful for the clinical
      diagnosis of parkinsonism and the staging scale scoring.

PMID- 8997135
TI  - [The intravascular mobile structure detected by duplex carotid ultrasonography in
      cardioembolic internal carotid artery occlusion].
AB  - We reported that duplex carotid ultrasonography demonstrated specific mobile
      intravascular mass in four patients with cardiac cerebral embolism. In all cases,
      duplex carotid ultrasonography clearly showed the presence of a mobile
      intravascular mass in the carotid artery within 2 days after the onset. In two of
      four cases, the follow-up duplex carotid ultrasonography showed disappearance of
      the previously observed "a mobile intravascular mass" 7 days after the onset. In
      the other two cases, a mobile intravascular mass became stable gradually and
      changed to non-mobile hyperechoic mass 10 days after the onset. We think that the
      intravascular mobile structure was probably a thrombus extending from the
      occlusive part of the internal carotid artery to the proximal side. We suspect
      that the specific "a mobile intravascular mass" detected by ultrasonography may
      help to diagnose embolic internal carotid artery occlusion.

PMID- 8997137
TI  - [Clinical and myopathological studies on rigid spine syndrome].
AB  - Rigid spine syndrome (RSS) is thought to be a group of heterogeneous muscle
      disorders. We reviewed the clinical and myopathologic findings of 55 patients
      with RSS including 49 previously reported and our own 6 patients. The results
      were as follows: the first, 80% showed restrictive ventilatory failure and 40%
      atrophy of the sternocleidomastoid muscle (SCM), which became manifest in the
      early stage of the illness, namely in less than 5 years from the onset. The
      second, paraspinal muscles usually began to be involved from the cervical
      semispinal muscle extending to other paraspinal muscles such as the more
      laterally located splenium muscle. The third, muscle biopsy demonstrated rimmed
      vacuoles (RV) in 41% of the 55 patients. RV were more frequently seen in the
      paraspinal muscles than the limb muscles, where marked myopathic changes of
      endomysial fibrosis and increased variation of the muscle fiber size were
      recognized. Based on the anatomical analysis of the paraspinal muscles, alligator
      sign, a radiological finding of the posterior opening between the cervical spine
      C1 and C2, seemed to result from the shortening of the cervical semispinal muscle
      due to its degeneration. This sign may, however, disappear as the whole
      paraspinal muscles including the semispinal muscles are affected. The RV seen in
      RSS seems to be a secondary, nonspecific structure related to the muscle
      degeneration. On the other hand, the above findings, namely the atrophy of SCM,
      restrictive ventilatory failure, and RV, have not been reported in Emery-Dreifuss
      muscular dystrophy (EDMD) so far. Accordingly, those findings and the absence of
      cardiac conduction abnormality are valuable for differential diagnosis of RSS
      from EDMD.

PMID- 8997138
TI  - [A case of Dyke-Davidoff-Masson syndrome with total hemiatrophy].
AB  - We reported a 39-year-old man with Dyke-Davidoff-Masson syndrome presenting with
      total hemiatrophy. The patient had a muscle defect in the left occipital lesion
      at birth and left hemiatrophy including the face in his infancy. The present
      illness consists of atrophy of the left face, trunk and extremities, a muscle
      defect accompanied with scleroderma of the left dorsal cervical lesion, bilateral
      pes cavus, cleft palate, left hemiparesis, including facial palsy and diminished
      superficial sensation of the left side of the body. Decrease in right cranial
      volume and slight elevation of the right temporal pyramid and the superior border
      of the orbit were seen on the X-ray study of the head. Atrophy of the right
      cerebrum and cerebral peduncle was seen on magnetic resonance imaging. These
      findings suggest that hemiatrophy of the brain was responsible for total
      hemiatrophy of the body in this patient. The etiology of cerebral hemiatrophy is
      not known. There is only a report of Dyke-Davidoff-Masson syndrome accompanied
      with total hemiatrophy.

PMID- 8997140
TI  - [A case of neuroborreliosis with unilateral radiculoneuropathy and elevated serum
      antibodies for Borrelia garinii and Borrelia afzelii].
AB  - A 24-year-old male patient was admitted to our hospital because of dysesthesia
      and weakness of the right leg. Six weeks before admission he traveled to southern
      China. A week later he noticed multiple papules with itching on his right leg
      that were suspected to be insect bites. Four days later numbness of the right leg
      developed. Then he began to limp because of the leg weakness. Two weeks before
      admission severe pain in the right leg developed. On admission neurological
      examination revealed hypesthesia, muscle weakness and atrophy, areflexia,
      radicular pain and Lasegue sign of the right leg, and patchy hypesthesia of the
      left leg. The cranial nerves were intact, and meningeal signs were negative.
      Complete blood counts and serum biochemistry were unremarkable except for
      eosinophilia and mild elevation of IgE. A test for antinuclear antibody was
      positive. Cerebrospinal fluid was normal. Nerve conduction study and sural nerve
      biopsy showed multifocal severe axonopathy. Although antibody for Borrelia
      burgdorferi sensu stricto was negative, antibodies for B. garinii and for B.
      afzelii were positive in serum immunoblotting. Neurological symptoms improved
      after administration of intravenous ceftriaxon following oral doxycycline. In
      Japan, this is the second case of neuroborreliosis not due to B. burgdorferi
      sensu stricto. To test antibodies for B.garinii and for B. afzelii is recommended
      in patients with suspected neuroborreliosis.

PMID- 8997139
TI  - [Neuroradiological findings of sporadic olivopontocerebellar atrophy with marked
      laterality and degenerative changes in the corticopontine tract].
AB  - We report a case of sporadic olivopontocerebellar atrophy (OPCA) with marked
      laterality of cerebellar atrophy and degenerative changes in the corticopontine
      tract. A 35-year-old man was admitted to our hospital for evaluation of
      titubation, gait disturbance, dysarthria, and urinary and fecal incontinence.
      Neurological examination showed a wide based gait, slurred speech, truncal
      ataxia, slightly saccadic ocular movement, and finger-to-nose incoordination,
      greater on the right than the left. Deep tendon reflexes were hyperactive and
      preserved with the right side greater than the left. Bilateral Babinski signs
      were present, and the patient had neurogenic bladder without orthostatic
      hypotension. Cranial MRI showed atrophy of the cerebellum with right dominance
      and of the pons. On T2- and PD-weighted images, high-intensity areas were
      detected at the left internal capsule, crus cerebri and ventral pons. These
      findings were compatible with the right dominance of the clinical symptoms. The
      high intensity area detected at the posterior internal capsule was more extensive
      than that seen in patients with motor neuron disease. This finding may coincide
      with the degenerative changes in the corticopontine tract. Moreover, 99mTc-HMPAO
      SPECT showed the crossed cerebello-cerebral diaschisis (CCCD) pattern, which
      indicates the decreased CBF in the right cerebellar hemisphere and the left
      frontal lobe. These findings may reflect degenerative changes in the
      corticopontine tract in OPCA.

PMID- 8997141
TI  - [A case of sympathotonic orthostatic hypotension following herpes simplex
      encephalitis].
AB  - The etiology of sympathotonic orthostatic hypotension (SOH) is still unknown. We
      reported a 50-year-old male case of SOH associated with herpes simplex
      encephalitis. Eight days before admission to our hospital, he noticed fever,
      which was followed by intractable hiccup. He was admitted to a local hospital,
      where nuchal rigidity and mononuclear CSF pleocytosis were noted. On the 9th
      hospital day, he suddenly developed respiratory arrest, and his consciousness
      state deteriorated to coma. He was transferred to our hospital with artificial
      ventilation on the same day. The second CSF examination revealed pleocytosis and
      positive herpes-simplex-virus antibody. CAT scan showed diffuse high density
      areas in the bilateral temporal lobes. Intensive anti-herpetic therapy was
      started. On the 14th hospital day, spontaneous respiration came back and
      consciousness state was improved from coma to stupor. He gradually recovered to
      alert state and became ambulatory by the 30th hospital day. Seven weeks after the
      onset of his illness, he noticed orthostatic dizziness for the first time during
      his rehabilitation exercises. Blood pressure was 116/78mmHg at supine position
      and 82/62mmHg at standing position, and the heart rate was 83bpm, and 141bpm,
      respectively. Plasma noradrenaline concentration was 0.09 ng/ml (within normal
      range) at supine position, but increased to 0.29ng/ml upon standing.
      Catecholamine infusion tests revealed hyposensitivity in beta 2-receptors;
      decrease in blood pressure in response to isoprenaline was blunted, while
      increase of blood pressure to noradrenaline was not impaired. Nerve conduction
      studies and sweating tests were normal. When he was discharged from our hospital
      on the 87th hospital day, he still had orthostatic symptoms. His complete
      recovery took full one year. Some authors claimed that SOH is an abortive form of
      acute autonomic neuropathy, while others postulated that it was due to unbalanced
      cardiovascular alpha- and beta-adrenoceptor functions. SOH of the present case
      seems to be caused by the central nervous lesions; especially, the brain stem
      involvement due to herpes simplex encephalitis may well be causing SOH.

PMID- 8997143
TI  - [Diameter decrement of abdominal aorta and redistribution of systemic blood flow
      in non-ambulant Duchenne muscular dystrophy patients].
AB  - Cardiomyopathy is a major life-threatening complication in Duchenne muscular
      dystrophy (DMD). Cardiac output is always low in advanced stage patients.
      Impaired muscles presumably require extremely low circulation, while blood flow
      to brain and internal organs is probably maintained. Therefore, the
      redistribution of systemic circulation must be another important factor which
      determines whether or not the cardiomyopathy results in fatal heart failure.
      Although great efforts have been focused on the cardiac function, this problem
      has seldom attracted attentions. Assuming that diameter of blood vessels reflects
      blood flow, we measured the diameter of abdominal aorta on CT at four levels: 1)
      beginning of the abdominal aorta, 2) before and 3) after the branching of renal
      arteries, 4) before bifurcation of the common iliac arteries. Six bed-ridden DMD
      patients were compared with 10 ambulant patients suffering from other
      neurological and non-neurological diseases. We obtained following results. First,
      the diameter of abdominal aorta is significantly smaller in DMD patients. Second,
      the decrement is most prominent between before and after the branching of the
      renal arteries. These results clearly showed predilection of renointestinal
      circulation at the sacrifice of lower extremities. This narrowing of distal aorta
      was also observed in Kugelberg-Welander disease and understood as a sequelae of
      longstanding abolition of lower extremity functions.

PMID- 8997142
TI  - [A case of progressive continuous muscular rigidity and painless and rhythmic
      muscle spasm associated with autoantibody against glutamic acid decarboxylase].
AB  - We described a 60-year-old man with 5-year history of insulin dependent diabetes
      mellitus who developed continuous rigidity of truncal muscle and painless,
      rhythmic muscular spasm of trunk and proximal lower and upper extremities. The
      rigidity continued even in sleep. The painless muscle spasm was often
      precipitated by volitional movement and emotional stimuli. Intravenous
      administration of diazepam strongly attenuated the muscle spasm as well as
      truncal rigidity. Surface electromyography showed the continuous contraction of
      abdominal and paraspinal muscles. The rhythmic, clonic spasm of shoulder, triceps
      brachii, intercostal, abdominal, paraspinal and quadriceps femoris muscle induced
      by voluntary neck flexion was not compatible with typical stiff-man syndrome.
      Antibody against glutamic acid decarboxylase (GAD) was detected in the serum and
      cerebrospinal fluid of this patient. His condition was getting well with oral
      intake of sodium valproate. While painless, rhythmic spasm and persistent
      rigidity during sleep ruled out the patient from typical stiff-man syndrome, he
      was supposed to have the same pathophysiological mechanism as the anti-GAD
      autoantibody positive stiff-man syndrome.

PMID- 8997144
TI  - [Effects of age and sex on orthostatic change of blood pressure in normal
      persons].
AB  - Orthostatic change of systolic blood pressure was consecutively recorded using
      oscillometric method in 140 normal persons aged twenties to eighties and analyzed
      by age and sex. Systolic blood pressure generally increased after standing. The
      men, especially over the age of 50, failed to increase blood pressure immediately
      after standing (initial 1-3 minutes), and then increased. In the women, on the
      other hand, blood pressure generally increased after standing. The mean ratio of
      the blood pressure elevation for 10 minutes was higher in the women than in the
      men over 50 years old. Systolic blood pressure tended to fall immediately after
      the second supine from standing in both sexes. In conclusion, age and sex may
      influence orthostatic change of blood pressure.

PMID- 8997146
TI  - [The effect of a water-cooled vest on heat intolerance in a patient with
      anhidrosis due to familial amyloidosis of Finnish type].
AB  - The patient was a 70-year-old male with familial amyloidosis of Finnish type who
      complained of heat intolerance due to anhidrosis during outdoor activities in
      summer. A water-cooled TM-2 vest was tried for this patient to reduce his body
      heat during exercises. Following the morning activities including jogging in
      August his body temperature rose up to 38.0 degrees C without wearing the partly
      frozen vest. However, when he wore it, his temperature rose up to only 37.2
      degrees C after the exercises, which was 0.8 degree C lower than when he did not
      wear the vest. Headache and tachycardia during and following the morning
      activities did not appear by wearing the vest. In the heat loading test, in which
      the room temperature was raised from 28.0 degrees C to 38.0 degrees C for 15
      minutes and kept at 38.0 degrees C for 60 minutes with 60% humidity, the rises of
      his skin and esophageal temperatures with wearing the partly frozen vest for the
      last 60 minutes were 1.2 degrees C and 0.4 degree C lower, respectively, than his
      skin and esophageal temperatures without wearing it. Concomitantly, the increase
      of heart rate was suppressed in the same test condition. Wet vest in running
      water showed the similar effects. Therefore, we concluded that the use of water
      cooled TM-2 vest was effective in alleviating the symptoms and signs of his heat
      intolerance.

PMID- 8997145
TI  - [A case of paranasal sinusitis-cavernous sinusitis with ophthalmoplegia externa].
AB  - A 15-year-old man was admitted because of diplopia and bilateral ptosis which
      occurred a few days after initial clinical signs, such as fever up, nausea,
      vomiting and headache. His pupils were anisocoric (Rt. phi 3.5 mm < Lt. phi 6.0
      mm). In his left eye, light reflex was absent and its movements were limited in
      all directions. Brain MRI revealed the findings of paranasal sinusitis in
      bilateral ethmoidal and sphenoidal sinuses and swelling of bilateral cavernous
      sinus. Combination of intravenous antibiotic therapy and drainage improved his
      clinical symptoms and MRI findings. It was diagnosed as the inflammation
      originated in the sphenoid and ethmoid sinuses, which extended to the cavernous
      sinus and then involved III, IV, and VI cranial nerves. In conclusion, MRI was
      very useful to detect the cavernous sinusitis secondary to sphenoidal sinusitis.

PMID- 8997147
TI  - [A case of bilateral infarction of medial pontomedullary junction].
AB  - A 69-year-old man suffered from dizziness and nausea after work, and was admitted
      to our hospital on the next day. On admission, he showed bilateral horizontal
      nystagmus and left hemiparesis. On the 3rd day he vomited frequently, and the
      dizziness became worse. Bilateral horizontal and upward gaze palsy and bilateral
      facial nerve palsy were observed. Brain MRI on the 5th day disclosed bilateral
      upper medial medullary infarction that extended to the pontomedullary junction.
      Cerebral angiography on the 13th day revealed occlusion of the right vertebral
      artery. This case did not show typical medial medullary syndrome. The mechanism
      was unknown, but similar cases were reported. Recently, many cases of medullary
      infarction are reported with the progress of MRI technology. It is suggested that
      the addition of the new concepts on the conventional syndromes of medullary
      infarction is necessary.

PMID- 8997148
TI  - [Sympathetic skin responses in the face by magnetic stimulation of the neck].
AB  - We studied the sympathetic skin responses (SSRs) in the face with magnetic
      stimulation of the neck, in 10 normal healthy subjects. The SSRs were recorded
      with surface electrodes placed on the forehead, the lower eyelid, the apex nasi,
      two points of cheek (one is near the ear, and another is near the mouth), the
      upper lip, and the lower jaw. Reproducible SSRs were obtained easily at the
      forehead and the upper lip compared to the other parts of the face. The SSRs on
      the forehead and upper lip were constantly evoked after drinking of hot water.
      Mean latencies are 0.98 +/- 0.22 sec. (mean +/- 1SD) at the forehead, and 0.89 +/
      0.12 sec. (mean +/- 1SD) at the upper lip. In the cervical sympathetic pathway,
      one part of postganglionic fibers runs along the internal carotid artery to
      innervate the eyelids and forehead, whereas another part runs along the external
      carotid artery to innervate other parts of the face. It suggests that the
      forehead and the upper lip are representative parts of those different
      innervations SSRs in the forehead and the upper lip could be useful for
      evaluating the sympathetic function of the face in various diseases.

PMID- 8997149
TI  - Drug reduction in the elderly.

PMID- 8997150
TI  - The Medication Reduction Project: combating polypharmacy in South Dakota elders
      through community-based interventions.
AB  - The Medication Reduction Project (MED RED) is a community-based program
      addressing polypharmacy issues in elders. Using educational presentations and one
      on-one medication reviews conducted by a pharmacist specializing in geriatrics,
      MED RED reached over 1,100 older adults in rural and urban southeastern South
      Dakota communities during 1993. Analysis of the longitudinal data indicate that
      older adults participating in one-on-one reviews were on fewer medications, had
      dosage reductions, were more likely to take their medications as directed, and
      increased their use of non-pharmacological alternatives. These elders also
      reported feeling better, spent less money per month on medications, and offered
      indications of improved functioning and increased levels of independence. These
      findings suggest that education about medication use is a dynamic tool in
      empowering community-based older adults to be assertive participants in their own
      health care.

PMID- 8997152
TI  - General principles of acute poisonings.

PMID- 8997153
TI  - Childhood tobacco use: a 1996 update.

PMID- 8997154
TI  - TennCare Partners Program--preparing for more change.

PMID- 8997151
TI  - Improving rural health care in South Dakota.
AB  - This study was designed to find ways to improve the quality of health care in
      rural settings. The study includes three components: a telephone survey of a
      rural community, a patient quiz, and interviews with ten rural family practice
      doctors in the southeast corner of South Dakota. This study was conducted in a
      rural community of about 1,500 people. The results of the survey suggest that
      rural health care can be improved by more education of the public on what is
      offered for preventative medicine, especially for the men 55 or younger, a female
      doctor who is willing to do obstetrical/gynecological services to meet the local
      demand, and physicians learning new procedures such as colonoscopy, colposcopy,
      and stress testing to better serve their patients.

PMID- 8997155
TI  - Was forewarning ignored?

PMID- 8997156
TI  - Adult-onset focal dystonias: presentation and treatment options.
AB  - Adult-onset focal dystonias (AFD) are common disorders that are often
      misdiagnosed and incorrectly treated. Their presentation is readily recognized,
      and botulinum toxin has become the agent of choice for treating these disorders.
      Most of the focal dystonias include cervical dystonia, blepharospasm,
      oromandibular dystonia, spasmodic dysphonia, and limb dystonia, specifically
      writer's cramp. Their onset is either idiopathic, familial, or post-traumatic,
      and the pathophysiology of the focal dystonias is not currently known. Local
      injections of botulinum toxin into the affected area result in chemical
      denervation of the muscle, resulting in a weakness of the muscles that are
      involved in the sustained contractions. This weakness alleviates the painful
      contraction of the dystonia. In this paper we present a case study of the most
      common type of focal dystonia, cervical dystonia. The etiology in this case was
      post-traumatic, and significant improvement resulted after treatment with
      botulinum toxin type A.

PMID- 8997157
TI  - Stroke prevention in non-rheumatic atrial fibrillation.
AB  - Warfarin can strikingly prevent stroke in patients with NRAF with or without a
      history of stroke or TIA. The target degree of anticoagulation is an INR between
      2.0 and 3.0. Any degree of anticoagulation with less than an INR of 2.0 will not
      provide full protection, any greater anticoagulation is no more effective, and an
      INR greater than 4.0 increases the risk of hemorrhage. Patients 65 years or
      younger without any risk factor do no better with warfarin than with aspirin or
      placebo, and should not be anticoagulated. All older patients or those with risk
      factors but without contraindications gain significant stroke prevention with
      warfarin anticoagulation as recommended above.

PMID- 8997158
TI  - Pulmonary hypertension associated with cirrhosis.

PMID- 8997159
TI  - Evolution of our understanding of the importance of elevated systolic blood
      pressure.

PMID- 8997160
TI  - Recommendations for the appropriate use of fluoride products. Tennessee
      Department of Health.

PMID- 8997161
TI  - Peritoneoscopic liver biopsy findings in asymptomatic chronic HBsAg carriers with
      normal liver function tests and no hepatomegaly.
AB  - Asymptomatic chronic HBsAg carriers with normal liver function tests are, in
      general regarded as having no liver pathology. Most of the histologic findings in
      asymptomatic chronic carriers have been reported from areas with low incidence of
      Hepatitis B virus (HBV) infection, such as North America and Western Europe. It
      is well known that there are many differences in HBV infection between low and
      high endemic areas, but there have been few reports on the histologic findings of
      asymptomatic chronic HBsAg carriers from endemic areas. The present study was
      undertaken in Korea which is one of the endemic areas for HBV infection and was
      designed to assess the prevalence of chronic liver disease by peritoneoscopic
      liver biopsy among asymptomatic chronic HBsAg carriers and to make a basis for
      the follow-up of asymptomatic chronic HBsAg carriers according to the results
      obtained. One hundred and ten asymptomatic HBsAg-positive carriers with normal
      liver function tests and no hepatomegaly were included in the study. Final
      diagnosis by peritoneoscopic liver biopsy revealed that of the 110 asymptomatic
      carriers only 27 (24.5%) had a histologically normal liver, while 51 (46.4%) had
      chronic liver diseases, and the remaining 32 (29.1%) had nonspecific histologic
      abnormalities (nonspecific reactive changes in 18 cases, cholestasis in 6 cases,
      and fatty change in 8 cases). Of the 51 patients with chronic liver diseases, 3
      had liver cirrhosis, 4 chronic active hepatitis with cirrhosis, 11 chronic active
      hepatitis and 33 chronic persistent hepatitis. The frequency of liver cirrhosis
      and chronic active hepatitis with cirrhosis was significantly high in the over 30
      years of age group (12.1%) than in the under 30 years of age group (0%; p = 0.011
      by Fisher's exact test). In conclusion, 46.4% of the Korean asymptomatic chronic
      HBsAg carriers with normal liver function tests and no hepatomegaly had chronic
      liver disease. This finding contrasted with reports from low incidence areas of
      HBV infection. Our results suggest that in endemic areas, a liver biopsy should
      be considered to assess the status of liver disease in asymptomatic chronic HBsAg
      carriers even if liver function tests are normal and hepatomegaly is absent, and
      the result can be used as a basis for the follow-up of each asymptomatic chronic
      HBsAg carriers.

PMID- 8997163
TI  - The effects of SS-cream and its individual components on rabbit corpus cavernosal
      muscles.
AB  - SS-cream (Severance Secret cream) is made up of extracts from 9 natural products
      for treating premature ejaculation (PE). SS-cream has been proved to be effective
      in the treatment of PE in pilot clinical studies. It has also been found to have
      a potentiating effect of their erectile capacity in some patients. Therefore, we
      investigated the pharmacological actions of SS-cream and the extracts of its
      individual components in rabbit corpus cavernosal smooth muscle to realize the
      effect of SS-cream on penile erection. Extracts of Bufonis Venenum induced a dose
      related contraction of rabbit corpus cavernosal muscle, which was significantly
      inhibited by phentolamine. Extracts of Caryophylli Flos induced a dose-related
      relaxation in the muscle strips precontracted with phenylephrine (5 x 10(-6)M;
      PHE). Caryophylli Flos caused a dose-dependent inhibition of the PHE induced
      contraction and also inhibited the contractility of Bufonis Venenum. Other
      extracts, when used individually or in a mixture, induced a dose-related
      relaxation in the precontracted muscle strips with PHE. SS-cream began to exert a
      relaxing effect at the concentration of 0.05 mg/ml in the muscle strips
      precontracted muscle strips with PHE (5 x 10(-6)M); causing dose-dependent
      relaxation with a maximal effect at 0.2 mg/ml. The relaxation effect of SS-cream
      was partially inhibited by endothelial disruption and by pretreatment with
      methylene blue, pyrogallol, atropine, and indomethacin, although they were not
      statistically significant. The results show that SS-cream has a relaxing effect
      on cavernosal smooth muscle. And it is partly related with enhancing the
      NO/cyclic GMP pathway although the relaxation mechanism in detail remains to be
      elucidated. Therefore, SS-cream may be effective for future treatment of mild
      erectile dysfunction, in addition to its role for premature ejaculation.

PMID- 8997162
TI  - The effects of high glucose concentration on angiotensin II- or transforming
      growth factor-beta-induced DNA synthesis, hypertrophy and collagen synthesis in
      cultured rat mesangial cells.
AB  - Hyperglycemia is a principal characteristic of diabetes, and has an influence on
      many cellular functions. In order to investigate whether the intracellular
      signaling pathways inducing proliferation, hypertrophy and matrix synthesis of
      mesangial cells are altered in a diabetic environment, we evaluated the effects
      of a high concentration of extracellular glucose(25 mM; 450 mg/dl) on
      [3H]thymidine uptake, hypertrophy, and [3H]proline incorporation into a
      collagenase-sensitive protein, induced by angiotensin II(Ang II) or transforming
      growth factor(TGF)-beta, in cultured rat mesangial cells. The exposure to a high
      glucose concentration for 7 days significantly inhibited Ang II(10(-6) M)-induced
      [3H]thymidine uptake, compared to normal glucose concentration (5 mM)(M +/- SD.,
      1050 +/- 100 cpm/well vs 550 +/- 97, p < 0.05), and markedly prevented the
      inhibition of [3H]thymidine uptake by TGF-beta(1 ng/ml)(132 +/- 10 vs 340 +/- 67,
      p < 0.05). The administration of H-7(50 microM), a protein kinase C(PKC)
      inhibitor, did not reverse these effects of high glucose on [3H]thymidine uptake.
      On flow cytometric analysis of cell size, the mean cell size was significantly
      greater for the cells exposed to high glucose or treated with Ang II or TGF-beta,
      compared to that for the untreated cells. But the addition of Ang II or TGF-beta
      to the cells exposed to high glucose did not show further enlargement in size.
      The exposure to high glucose and the treatment with Ang II or TGF-beta
      significantly increased collagen synthesis, measured by [3H]proline
      incorporation. The Ang II -or TGF-beta-induced increase of [3H]proline
      incorporation did not show changes under high glucose culture condition, compared
      to normal glucose concentration(Ang II, 27880 +/- 3560 cpm vs 26978 +/- 2284, TGF
      beta, 26559 +/- 3700 vs 25800 +/- 1660, p > 0.05). In conclusion, although the
      signaling pathway for DNA synthesis by Ang II or TGF-beta are influenced,
      possibly mediated by PKC-independent mechanism(s), the pathway inducing
      hypertrophy or collagen synthesis by both agents appears to be unchanged under
      the high extracellular glucose concentration in cultured rat mesangial cells.

PMID- 8997164
TI  - Gamma/delta T lymphocytes in the BCG granulomatous lesions.
AB  - Recent studies in man and animal models have demonstrated that TCR-gamma delta
      bearing T cells (gamma delta T cells) are activated by mycobacteria and
      accumulate in the sites of mycobacterial infection. Although the function of
      gamma delta T cells remains unclear, some data suggest a potential role for these
      cells in the granulomatous immune response. To address the presence of gamma
      delta T cells within the BCG granulomas, we have characterized the TCR phenotype
      of T-lymphocytes present in the BCG granulomatous lesion immunohistochemically
      using a monoclonal antibody to TCR delta 1 and others. Fairly large numbers of
      gamma delta T cells were located at the periphery of the BCG granulomas without
      necrosis and most of them also expressed CD8. However, gamma delta T cells were
      rarely present in the granulomas with central caseous necrosis, calcification and
      fibrotic changes. With these results, it might be speculated that the CD8+ gamma
      delta T lymphocytes participate in the BCG granuloma formation mainly in the
      early stage.

PMID- 8997165
TI  - The effects of cromakalim on the mediator releases from guinea pig lung mast cell
      activated by specific antigen-antibody reactions.
AB  - The inhibitory effect of cromakalim on the mediator release from mast cells
      caused by antigenantibody reactions was in controversy with the specific antigen
      used. However, it has recently been observed that cromakalim inhibits the release
      of mediators from superfused tracheal and parenchymal strips or lung mast cells
      after passive sensitization with the IgG1 antibody. An attempt, therefore, was
      made to determine the inhibitory mechanisms of cromakalim on the release of
      mediators such as histamine and leukotriene released by the activation of enzymes
      during mast cell activation. Guinea pig lung mast cells were purified through
      enzyme digestion, rough percoll and continuous percoll density gradients. The
      purified mast cells were prelabeled with [3H]palmitic acid. PLD activity was
      assessed more directly by the production of labeled phosphatidylethanol by PLD
      mediated transphosphatidylation in the presence of ethanol. In the cells labelled
      with [3H]myristic acid, [3H] DAG production was measured. The methyltransferase
      activity was assessed by measuring the incorporation of [3H]methyl moiety into
      phospholipids in sensitized mast cells labelled with L-[3H] methylmethionine.
      cAMP level was measured by radioimmunoassay. Cromakalim resulted in a decrease in
      the amount of histamine and leukotrienes releases by 30% in the ovalumin-induced
      mast cell. Cromakalim had little effect on phospholipase D activity enhanced by
      the activated mast cell. Cromakalim inhibited the initial increase of
      diacylglycerol production during mast cell activations. Cromakalim inhibited the
      phospholipid methylation increased in the activated mast cell. These results show
      that cromakalim decreases histamine release by inhibiting the initial increase of
      1,2-diacylglycerol during the mast cell activation, which is mediated via the
      phosphatidylinositide-phospholipase C system rather than the phosphatidylcholine
      phospholipase D system. Furthermore, cromakalim reduces phosphatidylcholine
      production by inhibiting the methyltransferase, which decreases the conversion of
      phosphatidylcholine into arachidonic acid and inhibits the production of
      leukotrienes.

PMID- 8997166
TI  - Isolation of perchloric acid soluble, heat stable, ethanol extractable protein
      from Mycobacterium tuberculosis.
AB  - The perchloric acid soluble, heat stable, and ethanol insoluble antigen of M.
      tuberculosis (TB-PBE) was prepared, and antigenicity of this antigen was studied
      in vivo and in vitro. TB-PBE showed a single band of 60 kDa by SDS-PAGE. Sera
      from the patients with active pulmonary tuberculosis did not react with this
      antigen by ELISA. A delayed hypersensitivity skin reaction was induced with this
      antigen and was correlated with the reaction with PPD. Skin biopsy was performed
      in this skin lesion induced by TB-PBE and stained by H-E and immunohistochemical
      methods. TB-PBE induced an inflammatory lesion similar to a lesion induced by
      PPD. Blastogenic activity of the peripheral blood mononuclear cells stimulated by
      TB-PBE increased, and showed a peak reaction at 7 days after stimulation. The
      blastogenic activity changed in a dose-dependent manner. After stimulation with
      TB-PBE, mononuclear cells were analyzed by FACS. DR+ T cells and CD4/CD8 ratio
      increased after stimulation by TB-PBE. These cells secreted IL-2, not IL-4 after
      stimulation with TB-PBE. In the immunofluorescence test, mouse antiserum against
      TB-PBE showed a positive reaction with M. tuberculosis and showed cross
      reactivity with M. bovis and other atypical mycobacteria, but not with S. aureus.
      With these results, it is evident that TB-PBE is an antigen which can induce cell
      mediated immunity in vivo and in vitro.

PMID- 8997167
TI  - Studies on bone markers and bone mineral density in patients with chronic renal
      failure.
AB  - Renal osteodystrophy has become a frequent complication in patients with chronic
      renal failure (CRF), and various histologic forms such as high turnover, low
      turnover and mixed bone disease have been demonstrated. The only reliable method
      for distinguishing patients with high turnover from those with low turnover bone
      disease is bone histomorphometric study, but its clinical utility is restricted.
      Because of its invasive nature, efforts have been made to predict indirectly the
      type and severity of this metabolic bone disease by serum assays. In this cross
      sectional study, we measured total and regional (head, arms, trunk, ribs, legs,
      spine and pelvis) bone mineral densities (BMD) by dual X-ray absorptiometry (DXA)
      in patients with variable degrees of CRF and correlated them with various bone
      markers. Decreased BMDs were detected in various skeletal sites (trunk and
      pelvis) in the patients' group. Total BMD Z score was lower in predialysis CRF
      patients than in the control subjects. Decreased BMD Z scores on weight-bearing
      bone were pronounced at L1 lumbar vertebra, femur trochanter, femur neck and
      Ward's triangle. Positive linear correlations were found between creatinine
      clearance and trunk, ribs, pelvis, and spine BMDs. There were inverse linear
      correlations between total BMD and total BMD Z score and alkaline phosphatase
      (AP), urine deoxypyridinoline (U-DPD) in the patients' group. There were no
      correlations between regional and total BMD, total BMD Z score and serum calcium,
      ionized calcium, and serum phosphate. There were inverse linear correlations
      between BUN, creatinine and bone-specific alkaline phosphatase in the predialysis
      CRF group. We evaluated the correlations between intact parathyroid hormone (i
      PTH) and biochemical and other bone markers. There was statistically significant
      linear correlation between i-PTH and AP. Other bone markers have no significant
      correlations with i-PTH. Our results demonstrated that there is significant bone
      loss in patients with CRF before the start of dialysis and also regional
      variations of BMDs in predialysis CRF patients. DXA is a useful method for
      evaluating regional and total BMDs and provides information about diverse
      regional skeletal changes. AP, i-PTH and U-DPD can predict BMD of predialysis CRF
      patients.

PMID- 8997168
TI  - Effects of intravenous immune globulin on the peripheral lymphocyte phenotypes in
      Kawasaki disease.
AB  - The effect of intravenous immune globulin (IVIG) on the lymphocyte phenotypes in
      acute Kawasaki disease (KD) was studied in a random trial of IVIG-and-aspirin
      versus aspirin-alone. Before therapy, patients in each treatment group had an
      increased percentage of B cells, and a decreased percentage of T cells, CD4 T
      cells, CD8 T cells and CD5+ B cells. There was no significant difference in
      immunologic parameters between the two groups measured before therapy. Patients
      treated with IVIG-and-aspirin had by the fourth day developed a highly
      significant increase in T cells, CD4 T cells and CD8 T cells and a decrease in B
      cells. Despite the decrease of B cells, there were significant increases in CD5+
      B cells in both treatment groups. However, the degree of increase in the IVIG-and
      aspirin treated group was significantly more noticeable than that in the aspirin
      alone treated group. These findings indicate that treatment with IVIG restores
      the T- and B- cell abnormalities, especially CD5+ B-cell abnormalities found in
      patients with acute KD.

PMID- 8997169
TI  - Reasoning strategies for suppositional deductions.
AB  - Deductive reasoning shares with other forms of thinking a reliance on strategies,
      as shown by the results of three experiments on the nature and development of
      control strategies to solve suppositional deductions. These puzzles are based on
      assertors who may or may not be telling the truth, and their assertions about
      their status as truthtellers and liars. The first experiment shows that reasoners
      make backward inferences as well as forward inferences, to short-cut their way
      through the alternatives, and the generation of suppositions is a source of
      difficulty. The second experiment establishes that the elimination of the
      suppositional status of an individual does not render problems easier. The third
      experiment shows that reasoners can improve their reasoning accuracy and speed
      spontaneously, without feedback, and it clarifies the transfer of strategies and
      their development. We discuss the implications of these data for alternative
      theories of suppositional deduction and for the relationship between reasoning
      and other forms of thinking such as problem solving.

PMID- 8997170
TI  - Pragmatics in understanding what is said.
AB  - A central claim in cognitive science is that speakers often say things which
      underdetermine what they imply by their use of utterances in context. For
      example, in uttering Jane has three children a speaker might only say that Jane
      has at least three children and may have more than three, but the speaker's
      utterance implicates that Jane has exactly three children. Many scholars
      following Grice have argued from such observations that pragmatics plays only a
      small part in determining what speakers say, as opposed to what they
      conversationally imply or implicate. We examined people's intuitions about the
      distinction between what speakers say, or what is said, and what they implicate
      by different indicative utterances, such as Jane has three children. The data
      from four experiments demonstrate that people do not equate a minimal meaning
      (i.e., Jane has at least three children and may have more than three) with what a
      speaker says, but assume that enriched pragmatics plays a significant role in
      determining what is said (i.e., Jane has exactly three children). People further
      recognize a distinction between what speakers say, or what is said, and what
      speakers implicate in particular contexts (e.g., Jane is married). These data
      lend support to theories of utterance interpretation in cognitive science that
      pragmatics strongly influences people's understanding of what speakers both say
      and communicate.

PMID- 8997171
TI  - The uncertain response in humans and animals.
AB  - There has been no comparative psychological study of uncertainty processes.
      Accordingly, the present experiments asked whether animals, like humans, escape
      adaptively when they are uncertain. Human and animal observers were given two
      primary responses in a visual discrimination task, and the opportunity to escape
      from some trials into easier ones. In one psychophysical task (using a threshold
      paradigm), humans escaped selectively the difficult trials that left them
      uncertain of the stimulus. Two rhesus monkeys (Macaca mulatta) also showed this
      pattern. In a second psychophysical task (using the method of constant stimuli),
      some humans showed this pattern but one escaped infrequently and nonoptimally.
      Monkeys showed equivalent individual differences. The data suggest that escapes
      by humans and monkeys are interesting cognitive analogs and may reflect
      controlled decisional processes prompted by the perceptual ambiguity at
      threshold.

PMID- 8997172
TI  - Reasons to doubt the present evidence for metaphoric representation.

PMID- 8997174
TI  - Analytical methods for the characterization and quality control of pharmaceutical
      peptides and proteins, using erythropoietin as an example.
AB  - In the last twenty years many peptides and proteins were introduced to the market
      for pharmaceutical use. The high complexity of the biomacromolecules requires the
      use not only of physicochemical methodologies but also of immunochemical and
      biological techniques for the characterization and quality control of these
      substances. Characterization of the active conformation and post-translational
      modifications is important for the understanding of the in vivo activity of
      peptides and proteins. Among other spectroscopic techniques circular dichroism
      has become a helpful tool for evaluating the secondary and tertiary structure of
      proteins and peptides. A combination of several analytical methods is necessary
      for a comprehensive characterization of the substance under investigation and for
      an appropriate quality control of the product concerning identity, purity and
      potency. Suitable analytical methodologies are discussed using erythropoietin as
      an example.

PMID- 8997173
TI  - Connectionism and the problem of systematicity (continued): why Smolensky's
      solution still doesn't work.
AB  - Paul Smolensky has recently announced that the problem of explaining the
      compositionality of concepts within a connectionist framework is solved in
      principle. Mental representations are vectors over the activity states of
      connectionist "units", but the vectors encode Classical trees, whose structural
      properties in turn "acausally" explain the facts of compositionality. This sounds
      suspiciously like the offer of a free lunch, and it turns out, upon examination,
      that there is nothing to it.

PMID- 8997175
TI  - Quality assurance after process changes of the production of a therapeutic
      antibody.
AB  - Process development for the production of a therapeutic humanised antibody is a
      very complex operation. It involves recombinant genetics, verification of a
      strong expression system, gene amplification, characterisation of a stable host
      cell expression system, optimisation and design of the mammalian cell culture
      fermentation system and development of an efficient recovery process resulting in
      high yields and product quality. Rapid progress in the field and the wish of some
      pharmaceutical companies for outsourcing their production are the driving forces
      for process changes relatively late in the development phase. This literature
      survey is aimed at identifying the limits of acceptable process changes in up
      scaling of the fermentation and down stream processing of biopharmaceuticals and
      defining the demand in production validation to prove product equivalency and
      identity of the isolated, purified therapeutic antibody.

PMID- 8997176
TI  - Degradation pathways, analytical characterization and formulation strategies of a
      peptide and a protein. Calcitonine and human growth hormone in comparison.
AB  - Peptides and proteins differ from conventional chemical entities in their
      sensitivity to numerous environmental factors and their susceptibility to
      different degradation pathways. Therefore, complex analytical methodologies are
      necessary to characterize their molecular entity as well as to detect and
      quantify the possible degradation products. The formulation of these molecules
      for a pharmaceutical product requires stabilization by various excipients. Most
      of the products are brought to market as solutions or lyophilisates. In the first
      part, this article presents a comparison between the degradation profile of a
      peptide (calcitonine) and a protein (human growth hormone), in solution and as a
      freeze-dried product. The various analytical methods used to characterize and
      identify the degradation products are reviewed and discussed. The second part
      contains an overview of the different formulation strategies for calcitonine and
      human growth hormone. Finally, the different stress conditions used to obtain
      stability data are discussed critically. This leads on to general comments on the
      design of stability studies for peptide and protein drugs as pharmaceuticals
      taking into consideration the official guidelines.

PMID- 8997178
TI  - Mechanisms of inhibition of insulin release.
AB  - Several agonists including norepinephrine, somatostatin, galanin, and
      prostaglandins inhibit insulin release. The inhibition is sensitive to pertussis
      toxin, indicating the involvement of heterotrimeric Gi and/or Go proteins.
      Receptors for the different agonists have different selectivity for these G
      proteins. After G protein activation, the alpha- and beta gamma-subunits
      dissociate and interact with multiple targets to inhibit release. These include
      1) the ATP-sensitive K+ channel and perhaps other K+ channels, 2) L-type voltage
      dependent Ca2+ channels, 3) adenylyl cyclase, and 4) a "distal" site late in
      stimulus-secretion coupling. The latter effect, which may be exerted close to the
      final stage of exocytosis, is the most powerful of the individual inhibitory
      mechanisms. G protein action on the target molecules is determined by the
      individual G proteins activated and their specificity for the targets. The L-type
      Ca2+ channel is inhibited by G(o)-1. Adenylyl cyclase is inhibited by Gi-2 and Gi
      3. The distal inhibition can be exerted by Gi-1, Gi-2, Gi-3, and G(o)-2. Thus
      there is both selectivity and promiscuity in G protein action in the beta-cell.
      These characteristics allow an inhibitory ligand to be effective at multiple
      targets and to act differentially from other inhibitory ligands.

PMID- 8997177
TI  - Special considerations concerning regulatory requirements and drug development
      for peptides and biotech products in the EU.
AB  - The marketing authorization for a new medicinal product is based on the
      scientific assessment of its quality, safety and efficacy. The marketing
      authorization application (MAA) which covers all the relevant documentation can
      be filed in the EU via different application procedures. For peptides and
      biological products special issues have to be taken into consideration during
      drug development. Due to special production procedures and the complexity of the
      active substance itself, peptides and biotech products are subject to specific
      regulatory requirements. This leads to the necessity to discuss the development
      program of a new peptide or biotech product with the health authorities on a case
      by case basis. This article will focus on the special regulatory requirements for
      peptides and biotech products including the registration procedures as well as
      technical, preclinical and clinical issues.

PMID- 8997179
TI  - Na+/Ca2+ exchange currents and SR Ca2+ contents in postinfarction myocytes.
AB  - Myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) had lower
      peak cytosolic free Ca2+ concentration ([Ca2+]i) and reduced maximal extent of
      cell shortening during contraction, but Ca2+ entry via L-type Ca2+ channels was
      normal. In the current study using whole cell patch-clamp technique, reverse
      Na+/Ca2+ exchange current (INa/Ca; 3 Na+ out:1 Ca2+ in) was measured in myocytes
      in which Na+, K+, and Ca2+ currents were blocked or minimized. Steady-state
      outward currents measured under these conditions increased with depolarization or
      with elevation of extracellular Ca2+ concentration ([Ca2+]o) from 1.8 to 5.0 mM,
      but were inhibited by 5 mM Ni2+ or by reduction of [Ca2+]i to near zero. In
      addition, reduction of cytosolic free Na+ concentration or of [Ca2+]i also
      decreased the amplitude of the outward current. These characteristics indicate
      the outward current was INa/Ca operating in reverse mode. Reverse INa/Ca was
      significantly lower in MI myocytes, especially at more positive voltages. In
      addition, sarcoplasmic reticulum (SR)-releasable Ca2+ content as estimated by
      integrating forward INa/Ca during caffeine-induced SR Ca2+ release was also
      significantly lower in MI myocytes. Depressed Na+/Ca2+ exchange activity may
      contribute to abnormal [Ca2+]i dynamics in MI myocytes.

PMID- 8997180
TI  - Characterization of the rabbit renal Na(+)-dicarboxylate cotransporter using
      antifusion protein antibodies.
AB  - Polyclonal antibodies were prepared against the rabbit renal Na(+)-dicarboxylate
      cotransporter, NaDC-1. The antibodies were raised in chickens against a fusion
      protein consisting of a 60-amino acid peptide from NaDC-1 and glutathione S
      transferase. These antibodies specifically recognized the fusion protein in
      Western blots and could immunoprecipitate the full-length NaDC-1 after in vitro
      translation. The antifusion protein antibodies specifically recognized a protein
      of 63 kDa in rabbit renal brush-border membrane vesicles (BBMV), similar to the
      predicted mass of 66 kDa. Two proteins of 57 and 115 kDa were recognized in
      rabbit intestinal brush-border membranes. A protein of 66 kDa was recognized in
      Xenopus oocytes injected with NaDC-1 cRNA. Enzymatic deglycosylation of rabbit
      renal BBMV resulted in a decrease in mass by 11 kDa, consistent with N
      glycosylation at a single site. Site-directed mutagenesis of the two consensus
      sequences for N-glycosylation in the NaDC-1 cDNA showed that Asn-576, located
      near the COOH-terminal, is glycosylated. The nonglycosylated mutant of NaDC-1
      exhibited 50% of wild-type succinate transport activity when expressed in Xenopus
      oocytes, suggesting that glycosylation is not essential for function. The revised
      secondary structure model of NaDC-1 contains 11 putative transmembrane domains
      and an extracellular glycosylated COOH-terminal.

PMID- 8997181
TI  - ATP activates a cation conductance and Ca(2+)-dependent Cl- conductance in Hensen
      cells of guinea pig cochlea.
AB  - Simultaneous whole cell patch-clamp and indo 1 fluorescence measurements were
      used to characterize ATP-evoked membrane currents and intracellular Ca2+
      concentration ([Ca2+]i) changes in isolated Hensen cells of the guinea pig organ
      of Corti. At negative holding potential, ATP activated a biphasic inward current
      and a concomitant increase in [Ca2+]i. The initial current activated within < 50
      ms, showed a reversal potential near 0 mV and was reversibly inhibited by 30
      microM suramin, suggesting this conductance was mediated by ATP-gated
      nonselective cation channels. The delayed ATP-activated current was mainly
      carried by Cl- as indicated by its shift in reversal potential when intracellular
      Cl- was replaced by gluconate. This Cl- conductance appeared to be Ca(2+)
      activated secondarily to Ca2+ influx, since it required the presence of
      extracellular Ca2+ and was suppressed when an intracellular solution containing
      10 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid was used. In the
      absence of extracellular Ca2+, ATP still increased [Ca2+]i concomitant with a
      monophasic inward cation current, indicating Ca2+ release from intracellular
      stores. We conclude that Hensen cells have ionotropic and metabotropic P2
      purinoceptors. They also have Ca(2+)-activated Cl- channels that can be activated
      by extracellular ATP, suggesting that purinoceptors in Hensen cells could play a
      regulatory role in ion and water balance of cochlear fluids.

PMID- 8997182
TI  - Continuous contractile activity induces fiber type specific expression of HSP70
      in skeletal muscle.
AB  - Continuous contractile activity of skeletal muscle elicits an early and dramatic
      increase in ribosomal RNA, suggesting that translational efficiency and/or
      capacity is enhanced during the adaptive response to increased metabolic demand.
      In view of the important role heat shock or stress proteins (HSPs) play as
      molecular chaperones during protein synthesis, we examined whether expression of
      the inducible 70-kDa HSP (HSP70) and/or mitochondrial 60-kDa HSP (HSP60) is
      altered in rabbit tibialis anterior muscle during continuous low-frequency motor
      nerve stimulation. Induction of the HSP70 gene was evident within 24 h after the
      onset of stimulation as reflected by increases in HSP70 transcription (> 20-fold)
      and mRNA (> 50-fold). HSP70 protein levels were significantly elevated (10- to 12
      fold) after 14 and 21 days of stimulation. Mitochondrial HSP60 mRNA and protein
      also increased during stimulation (> 18- and > 5-fold after 21 days,
      respectively). In situ hybridization and immunohistochemistry coupled with myosin
      ATPase staining revealed that expression of HSP70 was restricted to oxidative
      type I and IIa fibers during the first 3 days of stimulation but shifted to
      primarily type II fibers after 21 days of stimulation. These findings demonstrate
      that induction of HSP70 during the adaptive response to chronic motor nerve
      stimulation proceeds from type I/IIa to type IId(x)/b fibers, suggesting that the
      expression of HSPs may be required to support the folding and
      compartmentalization of nascent proteins during the transformation process.

PMID- 8997183
TI  - Carbonic anhydrase and cardiac pH regulation.
AB  - Membrane-bound carbonic anhydrase (CA) has recently been identified in mammalian
      cardiac tissue. In this study, we have investigated the histochemical location
      and functional role of CA in the ferret heart. Heart sections stained by a
      modified Hansson's technique showed CA to be located on capillary endothelial
      membranes as well as on sarcolemmal membranes. In the Langendorff-perfused heart,
      washout of CO2 brought about by switching perfusion between 25 mM HCO3(-)-5% CO2
      buffered solution and nominally HCO3(-)-CO2-free solution caused a transient rise
      in intracellular pH (pHi) measured by the chemical shift of 2-deoxy-D-glucose 6
      phosphate with 31P nuclear magnetic resonance spectroscopy. The initial rate of
      change of pHi, measured over the first 60-75 s of CO2 efflux, was significantly
      reduced from 0.41 +/- 0.03 pH units/min (n = 9) in control hearts to 0.28 +/-
      0.02 pH units/min (n = 5) in the presence of the membrane-permeable CA inhibitor
      6-ethoxzolamide (P < 0.05 compared with control) and to 0.22 +/- 0.04 pH
      units/min (n = 5) in the presence of the membrane-impermeable CA inhibitor CL
      11,366 (P < 0.01 compared with control). After reperfusion of the ischemic
      myocardium, both CA inhibitors caused a significant slowing of initial rate of
      change in pH (and initial rate of recovery of contractile function) compared with
      control hearts. These results suggest that CA, by facilitating the hydration
      dehydration of CO2-H2CO3, alters the relative concentrations of CO2 inside and
      outside the cells, thus enhancing the rate of CO2 transfer from the intracellular
      to extracellular compartments, which contributes significantly to pHi recovery
      after reperfusion of the ischemic myocardium.

PMID- 8997184
TI  - Effects of lost surface area on red blood cells and red blood cell survival in
      mice.
AB  - The effects of removing area from mouse red blood cells on the fate of the cells
      after reinfusion were investigated. When cells were made nearly spherical (by
      reducing cell area by approximately 35%) and then reinfused into the animal, most
      were cleared from the circulation within 1-2 h, although approximately 20% of the
      cells survived for 4 h or longer. When only 20% of the area was removed (leaving
      a 15% excess), more than 90% of the cells continued to circulate for 4 h. After
      reinfusion, the mean surface area of the surviving cells remained constant (73-75
      microns2), but the mean volume decreased, from 56.6 +/- 2.1 to 19.1 +/- 1.5
      microns3 (+/- SD of 5 replicates) over 4 h. These changes did not occur in cells
      suspended in plasma but not reinfused into the animal. Thus a loss of surface
      area results in a decrease in cell volume, as if to maintain a requisite degree
      of deformability. The results support the hypothesis that the increase in cell
      density associated with increasing cell age may be a consequence of surface area
      loss.

PMID- 8997185
TI  - Short-chain fatty acids inhibit cAMP-mediated chloride secretion in rat colon.
AB  - Butyrate stimulates salt absorption in mammalian colon. We examined whether
      butyrate also affects Cl- secretion. Mucosal segments of distal colon of male
      Sprague-Dawley rats and T84 cells were studied in Ussing chambers. In control
      colon, 1 mM dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) increased
      short-circuit current (Isc) and serosal-to-mucosal Cl- flux (JsmCl) by 3.2 +/-
      0.8 and 2.9 +/- 0.8 mueq.cm-2.h-1, respectively. Mucosal or serosal 25 mM
      butyrate prevented DBcAMP-induced increases in Isc and JsmCl. Four and eight
      millimolar butyrate caused half-maximal inhibition of the increases in JsmCl and
      Isc, respectively. Butyrate also inhibited basal JsmCl (by 2.0 +/- 0.4 mueq.cm
      2.h-1) but not carbachol-mediated Cl- secretion. The relative inhibitory potency
      at 25 mM of other short-chain fatty acids (SCFA) paralleled their degree of
      cellular metabolism: butyrate > acetate = propionate > isobutyrate. At 25 mM, all
      SCFA reduced mucosal intracellular pH (pHi) transiently by 0.1 pH unit. In intact
      T84 cells, 50 mM butyrate inhibited the DBcAMP-induced rise in Isc by 55%. In T84
      cells with nystatin-permeabilized basolateral membranes, butyrate inhibited the
      increase in Isc by 82%. We conclude that butyrate inhibits basal and cAMP
      mediated Cl- secretion by a mechanism independent of pHi, possibly located at the
      apical membrane.

PMID- 8997186
TI  - Proton currents in human eosinophils.
AB  - The killing of metazoan parasites by eosinophils involves the activation of a
      respiratory burst oxidase. To investigate whether human eosinophils possess an H+
      conductance that might participate in the extrusion of H+ generated by the
      respiratory burst, we employed the whole cell patch-clamp technique under
      conditions designed to isolate putative H+ currents. We observed a slow
      activation of outward currents by depolarizing voltage steps. The reversal
      potential (Erev) of the currents was a function of the H+ gradient, demonstrating
      that the current was carried by H+. The H+ conductance was activated by cytosolic
      acidification and reversibly blocked by divalent and trivalent cations. During
      large prolonged depolarizing voltage steps, the current activation was followed
      by a decrease in current. This was due to cytosolic H+ depletion, as evidenced by
      1) a change in Erev and 2) a cytosolic alkalinization. We also observed a rundown
      of the current, possibly due to the loss of a cytosolic factor necessary for H+
      current activity. An elevated pipette Ca2+ concentration (1 microM) activated the
      H+ conductance, suggesting that the cytosolic Ca2+ concentration is involved in
      the physiological regulation of H+ currents. The Ca(2+)-activated currents had
      properties similar to the currents observed at low Ca2+ concentrations (Erev,
      high-affinity block by Zn2+, kinetics of tail currents, kinetics of rundown). The
      Ca2+ effect might be mediated by phospholipase A2, inasmuch as 1) the currents
      were also activated by arachidonic acid, 2) the Ca2+ effect and the arachidonic
      acid effect were not additive, and 3) the Ca2+ effect, but not the arachidonic
      acid effect, was blocked by a phospholipase A2 inhibitor. Taken together, our
      results demonstrate that human eosinophils have large H+ currents that are
      activated by physiological intracellular signals. The electrophysiological
      properties of the H+ currents and their regulation strongly suggest that they
      participate in H+ extrusion during the respiratory burst.

PMID- 8997187
TI  - Sensitivity of volume-sensitive Cl- conductance in human epithelial cells to
      extracellular nucleotides.
AB  - The sensitivity to extracellular nucleotides of volume-sensitive Cl- channel
      activity was investigated by whole cell and single-channel patch-clamp recordings
      in a human small intestinal epithelial cell line (Intestine 407) during steady
      osmotic swelling. Adenine nucleotides added to the bathing solution suppressed
      whole cell volume-sensitive Cl- currents with the potency sequence of ATP > ADP >
      AMP. In contrast, extracellular adenosine 3',5'-cyclic monophosphate (cAMP) at
      over 0.1 mM increased volume-sensitive Cl- currents in the entire voltage range
      examined, whereas guanosine 3',5'-cyclic monophosphate was without effect.
      Neither the single-channel conductance nor the open probability was affected by
      extracellular cAMP. Extracellular ATP (at over 30 microM), in the Mg(2+)-free
      form, inhibited the whole cell volume-sensitive Cl- current, preferentially in
      the outward direction. By exposure to extracellular ATP, the single Cl- channel
      current became flickery at positive potentials. These results indicate that the
      volume-sensitive Cl- channel in the human epithelial cell is stimulated voltage
      independently by extracellular cAMP but blocked voltage dependently by the Mg(2+)
      free form of extracellular ATP.

PMID- 8997188
TI  - Ibuprofen protects human endothelial cell prostaglandin H synthase from hydrogen
      peroxide.
AB  - Human endothelial cells exposed to H2O2 demonstrate decreased prostacyclin (PGI2)
      synthesis due to decreased prostaglandin H synthase (PGH synthase) activity. We
      tested the hypothesis that PGH synthase activity could be protected from H2O2 by
      a reversible nonsteroidal anti-inflammatory drug. Experiments demonstrate that
      ibuprofen if present during H2O2 exposure, protects endothelial cell PGH synthase
      against the decrease in prostaglandin formation caused by H2O2. Additional
      studies demonstrated that decreasing arachidonic acid release from cell
      phospholipids during H2O2 exposure did not protect PGI2 synthesis following H2O2
      exposure. In other experiments, ibuprofen did not chelate Fe2+ in a conformation
      that inhibited the reactivity of Fe2+. In addition, ibuprofen did not scavenge
      HO. However, we demonstrate that ibuprofen significantly protects purified PGH
      synthase cyclooxygenase activity from the effects of H2O2. The results confirm
      the hypothesis. These findings suggest that ibuprofen displaces oxidant species
      from the cyclooxygenase site of PGH synthase, thereby preventing oxidation of the
      functional groups important for PGH synthase activity.

PMID- 8997189
TI  - CFTR-dependent membrane insertion is linked to stimulation of the CFTR chloride
      conductance.
AB  - We examined the relation between Cl current (Icl) stimulation and cell membrane
      capacitance (Cm) when cystic fibrosis transmembrane conductance regulator (CFTR)
      was expressed in Xenopus oocytes. ICl and Cm increased in parallel when oocytes
      expressing CFTR were stimulated by forskolin (10 microM) and 3-isobutyl-1
      methylxanthine (1 mM). The adenosine 3',5'-cyclic monophosphate (cAMP)-induced
      increase in surface area detected by Cm was confirmed by morphometry in the same
      oocytes used for the electrical recordings. These increases in ICl and Cm were
      reversible and were absent from control oocytes not injected with CFTR cRNA. The
      time to reach peak ICl lagged slightly behind the peak in Cm. ICl was varied by
      altering CFTR expression level or agonist dose or by expressing different CFTR
      mutants. In all cases, there was a close correlation between ICl and Cm, and the
      kinetics of ICl and Cm stimulation were more rapid the larger the magnitude of
      the stimulated current. The Cm-ICl relation for wild-type CFTR saturated,
      consistent with a limited capacity of cells to increase their surface area. These
      results indicate that stimulation of the CFTR ICl is linked closely to increases
      in membrane area. This suggests that CFTR is present in the membrane vesicles
      whose insertion is stimulated by cAMP. The contents of these vesicles may provide
      a link between activation of CFTR and its cAMP-dependent regulation of other
      channels.

PMID- 8997190
TI  - Nuclear magnetic resonance microscopy of single neurons under hypotonic
      perturbation.
AB  - Nuclear magnetic resonance (NMR) characteristics of water in perfused single
      neurons undergoing a 20% hypotonic perturbation were examined quantitatively
      using NMR microscopy. The transverse relaxation times (T2) in the cytoplasm and
      nucleus increased by 24.0 +/- 8.5% (average +/- SE, n = 8) and 29.7 +/- 5.3% (n =
      6), respectively, whereas the apparent diffusion coefficients (ADC) showed no
      significant change. These findings are consistent with the behaviors of a perfect
      osmometer and with accepted molecular relaxation and diffusion models and have
      significant impacts on current views of properties of cellular water.
      Furthermore, the results suggest that the increase of tissue intracellular-to
      extracellular volume ratio during cell swelling is the predominant mechanism
      underlying the ADC reduction in acute brain ischemia. These data are the first
      direct quantitative measurements of the NMR characteristics of water in the
      cytoplasm and nucleus of single cells undergoing physiological perturbations and
      may lead to an improved diagnostic capability for NMR imaging in a variety of
      disease states.

PMID- 8997191
TI  - Changes of actin cytoskeleton during swelling and regulatory volume decrease in
      cultured astrocytes.
AB  - Swelling of cultured astrocytes exposed to hyposmotic medium modified the
      organization of the filamentous actin (F-actin) cytoskeleton, making the actin
      network diffuse in the cell body but concentrated at foci corresponding to the
      tips of the cell projections retracted by swelling. This change was reversible,
      and, after 2 h, the actin cytoskeleton tended to recover, and cells regained
      their flat and stellate shape. Cytochalasins B and D (CB and CD, respectively),
      which disrupt the actin cytoskeleton, did not affect regulatory volume decrease
      (RVD) or the swelling-activated efflux of Cl- and inositol, although 10 microM CD
      increased the basal efflux of taurine. The mercurial p
      chloromercuribenzenesulfonate (0.5-1 mM), known to disrupt the membrane
      cytoskeleton in isosmotic conditions, induced a 46, 50, and 38% release of
      [3H]taurine, 125I, and [3H]inositol, respectively, causing cell shrinkage and
      retraction of the cytoskeleton. Coincidently, the swelling-stimulated release of
      [3H]taurine and 125I was reduced by 60 and 30%, respectively. Results of this
      study do not exclude the possibility that changes in the actin cytoskeleton
      elicited by swelling are involved in mechanisms of RVD and only indicate that the
      disruption caused by cytochalasins is unrelated to that process.

PMID- 8997192
TI  - Fiber-specific regulation of Ca(2+)-ATPase isoform expression by thyroid hormone
      in rat skeletal muscle.
AB  - We studied the effect of thyroid hormone (3,5,3'-triiodo-L-thyronine, T3) on the
      expression of sarcoplasmic reticulum (SR) fast- and slow-type Ca(2+)-ATPase
      isoforms, SERCA1 and SERCA2a, respectively, and total SR Ca(2+)-ATPase activity
      in rat skeletal muscle. Cross sections and homogenates of soleus and extensor
      digitorum longus muscles from hypo-, eu-, and hyperthyroid rats were examined,
      and expression of Ca(2+)-ATPase isoforms in individual fibers was compared with
      expression of fast (MHC II) and slow (MHC I) myosin heavy chain isoforms. In both
      muscles, T3 induced a coordinated and full conversion to a fast-twitch phenotype
      in one-half of the fibers that were slow twitch in the absence of T3. The
      conversion was partial in the other one-half of the fibers, giving rise to a
      mixed phenotype. The stimulation by T3 of total SERCA expression in all fibers
      was reflected by increased SR Ca(2+)-ATPase activity. The time course of the T3
      induced changes of SERCA isoform expression was examined 1-14 days after the
      start of daily T3 treatment of euthyroid rats. SERCA1 expression was stimulated
      by T3 at a pretranslational level in all fibers. SERCA2a mRNA expression was
      transiently stimulated and disappeared in a subset of fibers. In these fibers SR
      Ca(2+)-ATPase activity was high because of high SERCA1 protein levels. These data
      suggest that the ultimate downregulation of SERCA2a expression, which is always
      associated with high SR Ca(2+)-ATPase activities, occurs at a pretranslational
      level.

PMID- 8997194
TI  - A role for a background sodium current in spontaneous action potentials and
      secretion from rat lactotrophs.
AB  - We have used the perforated-patch variation of whole cell patch-clamp techniques,
      measurements of cytosolic calcium with use of fura 2, and secretion measurements
      with use of the reverse-hemolytic plaque assay to address the role of
      depolarizing background currents in maintaining spontaneous action potentials and
      spontaneous secretion from rat lactotrophs in primary culture. Replacement of
      bath sodium with tris(hydroxymethyl)aminomethane or N-methyl-D-glucamine caused a
      dramatic hyperpolarization of the cells, a cessation of spontaneous action
      potentials, and an increase in input resistance of cells. Tetrodotoxin had no
      effect on spontaneous action potentials, and removal of bath calcium stopped
      spiking but did not hyperpolarize the cells. The hyperpolarization in response to
      removal of bath sodium was associated with a decrease in cytosolic calcium
      levels. Finally, removal of bath sodium caused a decrease in spontaneous
      secretion of prolactin from lactotrophs. These data suggest that a background
      sodium current is essential to drive the membrane to threshold for firing
      spontaneous calcium-dependent action potentials in lactotrophs. This, in turn,
      results in elevated intracellular calcium, which supports spontaneous secretion
      of prolactin from these cells.

PMID- 8997193
TI  - Study of nonspecific cation channel coupled to P2z purinergic receptors using an
      acid load technique.
AB  - The intracellular pH (pHi) of rat submandibular cells was measured by 2',7'
      bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). The cells recovered from
      ammonium (30 mM) prepulse to their resting pHi within 10 min.
      Ethylisopropylamiloride (EIPA), an inhibitor of the Na+/H+ exchanger, slows the
      rate of pHi recovery. ATP (1 mM), in the presence of EIPA, increases the rate of
      recovery 3.7-fold in the absence or presence of ethylene glycol-bis(beta
      aminoethyl ether)-N,N,N',N'-tetraacetic acid. The recovery was blocked by the
      addition of 5 mM Mg2+ or 10 microM Coomassie blue. The response was elicited by
      2'- and 3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate but not by ADP, UTP,
      adenyl (beta-gamma-methylene)-diphosphonate, 2-methylthioadenosine 5'
      triphosphate, or muscarinic or beta-adrenergic agonists. The purinergic response
      was also observed when the cells were acidified by sodium propionate and could
      not be mimicked by the depolarization of the plasma membrane. Aluminum fluoride
      did not reproduce the response to ATP, suggesting that the observed response does
      not involve a high-molecular-weight GTP-binding protein. It is concluded that the
      activation of P2z receptors, probably by the opening of nonspecific cation
      channels, increases the permeability to protons in rat submandibular glands.

PMID- 8997195
TI  - Rapid effects of steroid hormones on free intracellular calcium in T84 colonic
      epithelial cells.
AB  - Studies from our laboratory have demonstrated rapid (< 1 min) nongenomic
      activation of K+ recycling and Na+/H+ exchange by mineralocorticoids in human
      colonic epithelium, and studies from other laboratories have demonstrated rapid
      effects of aldosterone on intracellular Ca2+ concentration ([Ca2+]i) in
      endothelial cells. Here a rapid nongenomic effect of aldosterone on [Ca2+]i is
      demonstrated in the human colonic epithelial cell line T84. Aldosterone induced a
      rapid increase in [Ca2+]i within approximately 2 min. The rise in [Ca2+]i after
      aldosterone appears to result from the activation of a Ca2+ influx pathway,
      inasmuch as 1) no increase in [Ca2+]i was observed with aldosterone when cells
      were bathed in Ca(2+)-free Krebs solution and 2) emptying of the intracellular
      Ca2+ stores by thapsigargin was not enhanced by addition of aldosterone to
      extracellular Ca(2+)-free solution. In contrast, the Ca2+ response to
      aldosterone, in the presence of 2 mM Ca2+ in the external bathing solution, was
      not decreased after intracellular Ca2+ stores were emptied by thapsigargin. Other
      mineralocorticoid hormones increased [Ca2+]i, whereas the glucocorticoid
      hydrocortisone failed to increase [Ca2+]i. These results demonstrate the
      existence of a mineralocorticoid-specific Ca(2+)-signaling pathway in human
      colonic T84 (crypt) epithelial cells.

PMID- 8997196
TI  - Ischemia-induced alterations in sarcoplasmic reticulum Ca(2+)-ATPase activity in
      rat soleus and EDL muscles.
AB  - To investigate the time-dependent effects of ischemia, as modified by muscle
      fiber type composition, on sarcoplasmic reticulum (SR) function, Ca(2+)-ATPase
      activity (total minus basal) was measured in homogenates prepared from samples
      obtained from rat soleus and extensor digitorum longus (EDL) muscle of ischemic
      and contralateral controls. Ischemia was induced by occlusion of blood flow to
      one hindlimb for periods of 1, 2, and 3 h (n = 10 per group). In EDL, maximal
      Ca(2+)-ATPase activity (expressed in mumol.g wet wt-1.min-1) was higher (P <
      0.05) in ischemic than in control at 1 h (80 +/- 10 vs. 56.5 +/- 5.3) and
      increased progressively with ischemia at both 2 h (88 +/- 4.6 vs. 53.1 +/- 2.8)
      and 3 h (116 +/- 3.8 vs. 67.8 +/- 3.2). In contrast, in soleus, increases (P <
      0.05) in Ca(2+)-ATPase activity with ischemia were observed at 2 h (19.2 +/- 0.86
      vs. 14.0 +/- 0.56) and 3 h (19.9 +/- 1.4 vs. 12.4 +/- 0.62) but not at 1 h (10.7
      +/- 1.5 vs. 10.0 +/- 0.83). In both EDL and soleus, basal Mg(2+)-ATPase was
      unchanged with ischemia. On the basis of these findings, it can be concluded that
      ischemia results in an increase in the maximal SR Ca(2+)-ATPase activity but that
      the time course of the change is dependent on the fiber type composition of the
      muscle.

PMID- 8997197
TI  - Mutations in the pore region of ROMK enhance Ba2+ block.
AB  - The sequence of the hydrophobic "P" (pore) region of a K(+)-selective channel
      from the kidney (ROMK2) was altered to match that of the closely related inward
      rectifier (IRK1) channel by changing two amino acids, leucine (L) 117 and valine
      (V) 121, to isoleucine (I) and threonine (T), respectively. The mutant channel
      expressed in Xenopus laevis oocytes had an apparent inhibition constant at zero
      voltage [Ki(0)] in the presence of Ba2+ of 0.07 +/- 0.01 mM, which was more than
      50 times lower than the Ki(0) of the wild-type channel (4.7 +/- 1.0 mM). The
      increased sensitivity to Ba2+ was accounted for by the point mutation V121T.
      Single-channel measurements indicated that the increased affinity involved an
      increase in the on-rate for Ba2+ block and a decrease in the off-rate. Block by
      Ca+ was also enhanced. The single-channel conductance of the L1171/ V121T mutant
      was increased by 50%, whereas the degree of inward rectification, ion
      selectivity, and apparent affinity for K+ were essentially unchanged. When the
      neutral asparagine residue within the second putative membrane-spanning domain of
      the ROMK channel was substituted with aspartic acid, the corresponding amino acid
      in IRK1, the degree of inward rectification was enhanced but Ba2+ block and
      single-channel inward conductance were unaffected. Thus the site of Ba2+ binding
      appears to be distinct from the locus of internal Mg2+ block and from at least
      one of the sites that determines K+ conjuctivity.

PMID- 8997198
TI  - Effects of taxol on isolated rat hepatocyte metabolism.
AB  - Taxol is a natural product, isolated from Taxus brevifolia, with increasing
      clinical applications because of its potent antitumor activity. Although it is
      mainly metabolized in the liver, its effect on hepatocyte metabolism has been
      scarcely investigated. In this study, the response of isolated rat hepatocytes to
      taxol was evaluated by correlating the changes observed in global indexes such as
      viability and heat dissipation with those produced in oxygen consumption and
      intracellular metabolites (ATP, fructose 2,6-bisphosphate, and lactate). The
      results indicate that taxol reduces aerobic metabolism, which induces an
      insufficient increase of the ATP via anaerobic glycolysis. Moreover, incubations
      of isolated mitochondria with taxol indicate that the respiratory chain is
      directly affected by this drug.

PMID- 8997199
TI  - Both M1 and M3 receptors regulate exocrine secretion by mucous acini.
AB  - We investigated the role of M1 and M3 receptors in regulating exocrine secretion
      from acini isolated from rat sublingual glands. In secretion experiments, we
      derived affinity values (KB) from Schild regression analysis for the antagonists
      pirenzepine (61.0 nM) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 1.06 nM).
      The KB for 4-DAMP is similar to its affinity value [equilibrium dissociation
      constant from competition studies (Ki); 1.81 nM] determined from radioligand
      competition experiments. In contrast, the KB for pirenzepine is between its high
      affinity (17.6 nM) and low-affinity (404 nM) Ki values. In separate secretion
      experiments, we found that the M1 receptor antagonist, M1-toxin, induces a
      rightward shift in the concentration-response curve to muscarinic agonist and
      inhibits maximal secretion by 40%. The inhibitory effect of M1-toxin appears
      specific for M1 receptor blockade, since the toxin abolishes acinar high-affinity
      pirenzepine-binding sites and does not inhibit secretion induced by nonmuscarinic
      agents. Additional pharmacological studies indicate muscarinic receptors do not
      function through putative neural elements within isolated acini. Our combined
      results are consistent with both M1 and M3 receptors directly regulating mucous
      acinar exocrine secretion and indicate M3 receptors alone are insufficient to
      induce a maximal muscarinic response.

PMID- 8997200
TI  - Vascular endothelial growth factor affects permeability of brain microvessel
      endothelial cells in vitro.
AB  - Vascular endothelial growth factor (VEGF), which stimulates endothelial cell
      growth and induces hyperpermeability of the microvasculature, plays an important
      role in normal and tumor-vasculature development and tumor edema generation. In
      this study, we investigated the effect of VEGF on the permeability of cultured
      bovine brain microvessel endothelial cells (BMECs), an in vitro blood-brain
      barrier (BBB) model. We found that addition of purified VEGF to both the apical
      and basolateral sides of the BMEC monolayers increased the permeability of the
      monolayer to [14C]sucrose (approximately 3-fold). A more significant increase in
      permeability was observed when VEGF was applied to the basolateral side of the
      monolayer (3-fold) than to the apical side (1.5-fold). The permeability
      increasing activity of VEGF on the BMEC monolayers is both dose and time
      dependent. The VEGF-induced permeability increase in BMECs requires a long
      incubation time with VEGF, and the effect is durable. These results suggest that
      this cell culture system may be useful for exploring the role of VEGF in
      regulating the permeability of the BBB, for studying the mechanism of the
      permeability-increasing effect of VEGF on the endothelial cells, and for
      evaluating the strategies to regulate the activity of VEGF.

PMID- 8997201
TI  - Actin polymerization and depolymerization during apoptosis in HL-60 cells.
AB  - Little is known about the biochemical "machinery" responsible for the
      morphological features of apoptosis, although the cytoskeleton is presumed to be
      involved. Using flow cytometry, polyacrylamide gel electrophoresis, and
      fluorescence microscopy, we show that apoptosis induced by ultraviolet (UV)
      irradiation or 80 micrograms/ml etoposide correlates with early transient
      polymerization and later depolymerization of filamentous (F)-actin and dramatic
      changes in visible microfilament organization. Depolymerization of F-actin began
      before the formation of apoptotic bodies and was ultimately composed of decreases
      in both the detergent-insoluble (40%) and detergent-soluble (50%) pools of F
      actin. Dihydrocytochalasin B (H2CB), which blocked apoptotic body formation,
      depolymerized F-actin in the detergent-insoluble pool only. Visually, H2CB
      treatment disrupted microfilament organization, resulting in short, brightly
      stained microfilaments dispersed throughout the cytoplasm. In contrast, apoptotic
      cells contained a network of fine microfilaments with bright staining
      concentrated at the site of apoptotic body formation. Together, these results
      suggest that reorganization of the microfilament network is necessary for the
      formation of apoptotic bodies and that depolymerization of F-actin may also be a
      necessary component of the process of apoptosis.

PMID- 8997202
TI  - Ultrastructural and cytochemical characterization of cultured dogfish shark
      rectal gland cells.
AB  - The dogfish shark rectal gland (SRG) is histologically complex, containing
      connective, nerve, and smooth muscle tissue and at least three types of
      epithelial cells: secretory tubule, central duct, and endothelial. This cellular
      heterogeneity precludes studies of the intact SRG from distinguishing direct
      tubular effects of mediators that modulate chloride secretion from their indirect
      effects on nonepithelial cells such as neurons. Primary SRG cultures express high
      levels of secretagogue-stimulated chloride secretion, suggesting that SRG cells
      retain a significant level of cytodifferentiation in vitro. However, because
      nontubular cells could contaminate these cultures, the question of whether
      secretagogues activate chloride secretion through direct or indirect effects on
      tubular epithelial cells remains unresolved. To address this issue, detailed
      ultrastructural and cytochemical analyses of SRG cultures were carried out to
      assess the level of cellular heterogeneity and the degree of cytodifferentiation
      expressed by SRG cells in vitro. The results demonstrate that, after 15 days,
      primary SRG monolayer cultures are composed exclusively of tubular epithelial
      cells with no detectable contamination by central duct cells, fibroblasts, smooth
      muscle cells, endothelial cells, or neurons. Tubular epithelial cells express
      most of the structural features of native SRG cells, including numerous
      mitochondria, massive basolateral surface amplification, complex tight junctions,
      and an extensive tubulovesicular system in the apical cytoplasm. Cultured SRG
      cells also display a striking level of polarization of cytoplasmic organelles and
      plasma membrane secretagogue receptors. These results account for the
      exceptionally high rates of electrogenic chloride secretion by SRG tubular
      epithelial cells in vitro and confirm that the effects of secretagogues on
      transport activity reflect their direct interaction with tubular epithelial
      cells.

PMID- 8997203
TI  - Annexin VI modulates Ca2+ and K+ conductances of spinal cord and dorsal root
      ganglion neurons.
AB  - Annexin VI is a member of a Ca(2+)-dependent phospholipid-binding protein family
      that participates in the transduction of the intracellular Ca2+ signal. We have
      identified annexin VI as one of the major annexins expressed differentially by
      sensory neurons of dorsal root ganglia (DRG) and by neurons of spinal cord (SC)
      of the rat and the mouse. This annexin shows a preferential localization at the
      plasma membrane of the soma and cellular processes, particularly in motoneurons
      of the SC. This finding suggests an active role of annexin VI in the Ca(2+)
      dependent regulation of plasma membrane functions. To test this possibility, the
      neuronal function of annexin VI was evaluated by whole cell electrophysiology of
      mouse embryo SC and DRG neurons. An antibody was developed that has the property
      of neutralizing annexin VI-phospholipid interactions. The intracellular perfusion
      of individual neurons in culture, either from SC or DRG, with monospecific
      affinity-purified anti-annexin VI antibodies resulted in an increase in the
      magnitude of the K+ current and in an increase in the Ca2+ current in sensory
      neurons. Our results suggest that the endogenous annexin VI regulates the Ca2+
      conductance, which indirectly modifies Ca(2+)-dependent ionic conductances in SC
      and DRG neurons.

PMID- 8997204
TI  - Altered expression of myosin mRNA and protein in rat soleus and tibialis anterior
      following reinnervation.
AB  - Myosin heavy chain (MHC) expression was studied in rat soleus and tibialis
      anterior (TA) at the mRNA and protein levels following reinnervation 8 and 32 wk
      after sciatic nerve injury. A sciatic nerve crush or transection injury was
      produced in the midthigh region of adult female Sprague-Dawley rats. A
      ribonuclease protection assay was developed to measure four of the adult MHCs (I,
      IIa, IIx, IIb) in a single sample. MHC mRNA and protein were measured and
      compared in the same muscles. Eight and thirty-two weeks after a crush injury,
      the MHC mRNA profiles were similar to control with the exception of soleus MHC
      IIa and TA MHC IIb, which were significantly less than control at both time
      points. In contrast, reinnervation of the soleus following a sciatic nerve
      transection injury resulted in an MHC isoform shift characterized by increases in
      the relative amounts of fast myosin (IIa and IIx) and a decrease in slow myosin.
      As expected, significant changes first occurred at the mRNA level followed by
      changes in protein expression. Thirty-two weeks after transection injury and
      repair, the primary MHC mRNA isoform in the soleus was MHC IIx. Moreover, at 32
      wk, MHC IIb mRNA was detected in 50% of the reinnervated soleus following a
      transection injury. Reinnervation of the TA following sciatic nerve transection
      led to replacement of the MHC IIb isoform with MHC IIx.

PMID- 8997205
TI  - Myoglobin content and oxygen diffusion: model analysis of horse and steer muscle.
AB  - We test the hypothesis that myoglobin is important for O2 supply near the
      oxidative capacity of muscle. This hypothesis is evaluated with a simple model
      that incorporates the properties of heart and skeletal muscle tissue taken from
      steers and horses exercising at their maximum O2 consumption rate. These tissue
      samples allowed us to set the bounds on oxidative demand and O2 flux from red
      blood cells to the core of the muscle fiber, to estimate the blood and tissue
      capacities for O2 diffusion, and to define the capillary blood PO2 driving this
      O2 flux. A model combining blood convection with tissue diffusion indicates that
      O2 diffusion alone is insufficient to achieve the measured O2 fluxes in many
      samples. The myoglobin content of these fibers is significantly correlated with
      this O2 diffusion limitation and provides sufficient additional O2 flux to meet
      muscle O2 demand. The presence of myoglobin maintains the PO2 in the fiber core
      above anoxic levels for the majority of muscles. Thus myoglobin is critical to O2
      supply at fluxes near the maximum and prevents anoxia by maintaining PO2 above
      levels needed to support mitochondrial function.

PMID- 8997206
TI  - Induction of human myeloblastic ML-1 cell G1 arrest by suppression of K+ channel
      activity.
AB  - Our previous studies have shown that a voltage-gated K+ channel is highly
      expressed in proliferating human myeloblastic ML-1 cells and is suppressed in the
      early stages of 12-O-tetradecanoylphorbol-13-acetate-induced ML-1 cell
      differentiation. In the present study, we report that inhibition of the K+
      channel activity by 4-aminopyridine (4-AP) suppressed ML-1 cell proliferation, as
      measured by DNA synthesis. Cell cycle mapping indicated that ML-1 cells were
      arrested in G1 phase after 24-h treatment with 4-AP. Blockade of ML-1 cells at
      the G1/S boundary of the cell cycle with aphidicolin revealed that ML-1 cells
      past the G1 checkpoint were capable of entering S phase and synthesizing DNA
      independently of the channel blockade. ML-1 cell differentiation, measured by
      CD14 marker protein expression, revealed that the effect of 4-AP was to cause
      growth arrest and that it did not cause differentiation. Dephosphorylation of
      retinoblastoma protein accompanied inhibition of ML-1 cell proliferation and
      suggested that suppression of K+ channel activity by 4-AP is associated with
      retinoblastoma protein-mediated G1 arrest in ML-1 cells. Moreover, we found that
      ML-1 cell volume increased 35 +/- 7% after 4-AP treatment, which could be an
      early event triggering inhibition of ML-1 cell proliferation. These findings
      suggest that a 4-AP-sensitive K+ channel may play an important role in the
      transduction of mitogenic signals in ML-1 cells.

PMID- 8997207
TI  - Altered contractility of urinary bladder in diabetic rabbits: relationship to
      reduced Na+ pump activity.
AB  - We studied the effect of alloxan-induced diabetes on Na+ pump activity in
      isolated rabbit bladder strips. In addition, the effects of diabetes and the Na+
      pump inhibitor ouabain on contractions induced by carbachol (CCh) and KCl were
      studied. In bladder strips from diabetic rabbits, ouabain-sensitive 86Rb+ uptake
      (a measure of Na+ pump activity) was approximately 50% less compared with strips
      from normal bladder. Diabetes also reduced the maximum contractions induced by
      CCh and KCl. Treatment of bladder strips with ouabain alone caused an acute
      concentration-dependent increase in tone. In contrast, longer incubation with
      ouabain inhibited CCh- and KCl-induced contractions in normal and diabetic
      bladders. Furthermore, differences in agonist-mediated contractions observed
      between normal and diabetic bladders were abolished in the presence of the
      maximally effective concentration of ouabain (10 microM). The ability of CCh to
      cause contraction in normal and diabetic rabbit bladders was also significantly
      inhibited by the Na+ ionophore monensin but not by the Ca2+ ionophore A-23187 or
      by depolarization with KCl. Monensin also inhibited KCl-induced contractions in
      normal bladder strips. These results indicate that 1) Na+ pump activity is an
      important modulator of bladder smooth muscle tone, 2) diabetes diminishes Na+
      pump activity and inhibits agonist-induced contractions in bladder, and 3) an
      increase in intracellular Na+ concentration, secondary to inhibition of bladder
      smooth muscle Na+ pump activity, is associated with reduced responsiveness to
      contractile agonists. Diminished Na+ pump activity in diabetes may, in part,
      contribute to the development of bladder cystopathy.

PMID- 8997208
TI  - Oxygen dependence of respiration in coupled and uncoupled endothelial cells.
AB  - We studied the oxygen dependence of respiration in cultured human umbilical vein
      endothelial cells by use of high-resolution respirometry. The rate of oxygen
      consumption varied from 30 to 50 pmol O2.s-1.(10(6) cells)-1 over a sixfold range
      of cell densities. Respiration was stimulated up to 3.5-fold by uncoupling with
      carbonyl cyanide p-trifluoromethoxyphenylhydrazone or 2,4-dinitrophenol, and the
      PO2 at half-maximal respiration (P50) increased from 0.05 to 0.12 kPa (0.3 to 0.9
      Torr) with respiratory rate. P50 decreased to a minimum of 0.02 kPa when
      uncoupled cells were inhibited to control levels. Differences in cell size
      explained a variation of approximately 0.015 kPa in P50 at similar respiratory
      rates per cell. Oxygen diffusion to mitochondria contributed maximally 30% to the
      regulation of P50 in coupled cells, as deduced from the shallow slope of the flux
      dependence of P50 in uncoupled-inhibited cells compared with the slope in coupled
      cells. Therefore 70% of the flux dependence of P50 in coupled cells was caused by
      changes in metabolic state, which correlated with respiratory rate.

PMID- 8997209
TI  - Ca(2+)-force relationship of frog skeletal muscle: a dynamic model for parameter
      estimation.
AB  - A simple mathematical model describing the dynamic connection between Ca2+ and
      force generation in intact skeletal muscle from the frog has been developed from
      isometric force responses to cytosolic Ca2+ concentration ([Ca2+]c) transients
      during tetanic and twitch contractions. The main element of the model is a two
      state cross-bridge cycle characterized by the fractional rate of cross-bridge
      attachment (f(app)) and the fractional rate of cross-bridge detachment (g*).
      While g* is constant, f(app) is time varying and regulated by both [Ca2+]c and
      force. Having only four adjustable parameters, the model is mathematically
      unique, thereby allowing precise parameter estimation from the dynamic Ca2+ and
      force data. The model should be useful for developing insights into the relative
      importance for force generation and relaxation of 1) the size and shape of the
      Ca2+ transient, 2) the sensitivity of the fractional rate of cross-bridge
      attachment to both the [Ca2+]c and the force responses, and 3) the fractional
      rate of cross-bridge detachment, which is insensitive to both Ca2+ and force.

PMID- 8997210
TI  - L-ascorbic acid regulates growth and metabolism of renal cells: improvements in
      cell culture.
AB  - The addition of L-ascorbic acid 2-phosphate (AscP) to primary cultures of rabbit
      renal proximal tubular cells (RPTC) grown under improved culture conditions
      resulted in an extended growth phase and increased cellular density (1.3-fold
      increase in monolayer DNA and protein contents). AscP reduced glycolysis,
      increased net lactate consumption by 38%, and stimulated net glucose production
      by 47%. Basal O2 consumption increased by 39% in RPTC grown in the presence of
      AscP and was equivalent to that in freshly isolated proximal tubules. AscP
      increased ouabain-sensitive O2 consumption (81%) and Na(+)-K(+)-ATPase activity
      (2.5-fold), which suggested increased active Na+ transport. Addition of AscP
      increased Na(+)-dependent glucose uptake by 43% and brush-border enzyme marker
      activities by 46%. It is concluded that supplementation of media with AscP
      further improves RPTC culture conditions by promotion of cellular growth and
      stimulation of in vivo-like respiration, lactate utilization, and net glucose
      synthesis. These changes are accompanied by an increase in brush-border enzyme
      activities and stimulation of active Na+ transport and Na(+)-dependent glucose
      transport, which demonstrate an improved expression of brush-border membrane
      functions in RPTC.

PMID- 8997211
TI  - Dual-energy X-ray absorptiometry body composition model: review of physical
      concepts.
AB  - Although dual-energy X-ray absorptiometry (DXA) is widely used in clinical
      research as a means of quantifying body composition, there remains at present
      little published information that reviews the method's underlying physical basis.
      Because a clear understanding of DXA physical concepts is integral to appropriate
      use and interpretation, we present here a three-section review that includes both
      relevant in vitro and in vivo experimental demonstrations. In the first section
      we describe the main physical principles on which DXA is based. The section that
      follows presents a step-by-step analysis of the DXA two-component soft tissue
      model. In the final section we demonstrate how knowledge of physical concepts can
      lead to resolution of important methodological concerns, such as the influence of
      hydration changes on DXA fat estimates. A thorough understanding of DXA physical
      concepts provides a basis for appropriate interpretation of measurement results
      and stimulates many new and important research questions.

PMID- 8997212
TI  - Hepatic VLDL secretion of genetically obese Zucker rats is inhibited by a high
      fat diet.
AB  - Hepatocytes from obese and lean Zucker rats adapted to a control (C) or a high
      fat (HF) diet were prepared for the study of fatty acid (FA) uptake, partition
      between oxidation and esterification, and very low density lipoprotein (VLDL)
      production. A first 2-h kinetic study showed higher oleate uptake on a C diet by
      obese rat cells and an almost exclusive esterification to triacylglycerol (TG),
      VLDL secretion being 2.5-fold higher in obese rat cells and enhanced 1.4-fold in
      both genotypes in the presence of 0.7 mM oleate vs. 0.1 mM or no oleate. Fat
      feeding 1) decreased oleate uptake, esterification, incorporation into VLDL-TG,
      and mass VLDL-TG secretion and 2) abolished the VLDL-TG increase by 0.7 mM
      oleate. Similar but more pronounced effects were obtained in fat-fed lean
      animals. A second kinetic study using very short incubation times up to 1 h
      confirmed that fat feeding decreased oleate uptake and esterification, greatly
      stimulating its oxidation and production of acetoacetate (obese) or acetoacetate
      and beta-hydroxybutyrate (lean). Synthesis of lactate and pyruvate greatly
      decreased under HF feeding, remaining higher in obese rat cells. The drastic
      inhibition of labeled and total hepatic VLDL-TG secretion in obese and lean
      Zucker rats by the HF diet could be partly explained by decreased exogenous FA
      availability for VLDL-TG synthesis through its greater channeling toward
      oxidation and, indirectly, by the altered hepatocyte metabolic state.

PMID- 8997213
TI  - Postprandial leg and splanchnic fatty acid metabolism in nonobese men and women.
AB  - These studies were conducted to determine whether there are gender-specific
      regional differences in meal triglyceride fatty acid uptake. Systemic and
      regional oleate ([3H]oleate) kinetics were measured in nine nonobese men and
      eight nonobese women before and at the end of a 6-h meal, administered as small
      frequent feedings to achieve steady-state chylomicronemia. Chylomicron uptake in
      the splanchnic bed accounted for 71 +/- 15% of meal triglyceride disappearance in
      men and 20 +/- 7% in women (P < 0.01), whereas leg chylomicron uptake could only
      account for 12 +/- 2 and 8 +/- 4% (P not significant in men vs. women) of meal
      triglyceride disappearance. Meal ingestion suppressed (P < 0.05) systemic and
      regional free fatty acid release in both men and women. Splanchnic nonchylomicron
      triglyceride release and leg nonchylomicron triglyceride uptake were not
      significantly different in men and women. In summary, the largest quantitative
      difference between men and women in fatty acid kinetics during meal ingestion is
      a substantially greater splanchnic uptake of meal triglyceride fatty acids in
      men. This could represent greater meal fatty acid storage in visceral adipose
      tissue.

PMID- 8997214
TI  - Insulin-like growth factor I inhibits degradation and improves retention of
      protein in hindlimb muscle of lambs.
AB  - We infused recombinant human insulin-like growth factor I (IGF-I) for 4 h at 12.3
      micrograms.h-1.kg live weight-1 directly into the left femoral artery and
      measured the rates of synthesis, degradation, and gain of protein by the treated
      and contralateral limbs of well-fed (n = 8), feed-restricted (n = 10), and fasted
      (n = 9) castrated male lambs. Reducing feed intake decreased net protein gain of
      hindlimb muscle, reduced hindlimb glucose uptake, and lowered arterial plasma
      concentrations of IGF-I, insulin, glucose, phenylalanine, tyrosine, and
      isoleucine. The effect of nutrition on IGF-binding proteins (IGFBP) was generally
      small; IGFBP-2 was more abundant in fasted lambs. Infusion of IGF-I into the left
      femoral artery increased plasma levels of IGF-I 2- to 4-fold in the left femoral
      vein and by 1.5- to 3-fold in the artery and right femoral vein. In the treated
      limb, IGF-I reduced protein degradation, increased protein gain, and increased
      glucose uptake without altering blood flow or oxygen uptake, regardless of feed
      intake. Systemically, IGF-I reduced plasma insulin, phenylalanine, tyrosine,
      isoleucine, and leucine in all nutrition groups. Plasma IGFBP-3 was increased by
      4 h of IGF-I treatment in fasted but not in fed lambs. In fed but not fasted
      lambs, IGF-I increased blood glucose concentration. Effects of IGF-I on protein
      metabolism in the contralateral limb were affected by nutrition, generally more
      so in fasted than in unrestricted fed lambs.

PMID- 8997215
TI  - Fat and carbohydrate metabolism during exercise in elderly and young subjects.
AB  - We evaluated the effect of aging on fat and carbohydrate metabolism during
      moderate intensity exercise. Glycerol, free fatty acid (FFA), and glucose rate of
      appearance (Ra) in plasma and substrate oxidation were determined during 60 min
      of cycle ergometer exercise in six elderly (73 +/- 2 yr) and six young adults (26
      +/- 2 yr) matched by gender and lean body mass. The elderly group was studied
      during exercise performed at 56 +/- 3% of maximum oxygen uptake, whereas the
      young adults were studied during exercise performed at the same absolute and at a
      similar relative intensity as the elderly subjects. Mean fat oxidation during
      exercise was 25-35% lower in the elderly subjects than in the young adults
      exercising at either the same absolute or similar relative intensities (P <
      0.05). Mean carbohydrate oxidation in the elderly group was 35% higher than the
      young adults exercising at the same absolute intensity (P < 0.001) but 40% lower
      than the young adults exercising at the same relative intensity (P < 0.001).
      Average FFA Ra in the elderly subjects was 85% higher than in the young adults
      exercising at the same absolute intensity (P < 0.05) but 35% lower than the young
      adults exercising at a similar relative intensity (P < 0.05). We conclude that
      fat oxidation is decreased while carbohydrate oxidation is increased during
      moderate intensity exercise in elderly men and women. The shift in substrate
      oxidation was caused by age-related changes in skeletal muscle respiratory
      capacity because lipolytic rates and FFA availability were not rate limiting in
      the older subjects.

PMID- 8997216
TI  - Pancreatic islet blood flow in normal and obese-hyperglycemic (ob/ob) mice.
AB  - The present study evaluated whether a microsphere technique could be used for
      islet blood flow measurements in anesthetized mice. When this was confirmed, we
      applied the technique in different strains of mice. Approximately 9 x 10(4)
      microspheres could be given without interfering with mean arterial blood
      pressure. Mixing of the microspheres with arterial blood was adequate, and the
      extraction of microspheres in capillary beds was nearly 100%. In NMRI mice whole
      pancreatic blood flow was estimated to be 0.54 +/- 0.11 ml.min-1.g pancreatic
      tissue-1 and islet blood flow to be 18 +/- 4 microliters.min-1.g pancreas-1 (n =
      12 animals per experiment), whereas corresponding values in lean C57Bl/6 mice
      were twice as high. In C57Bl/6 mice glucose (3 g/kg iv) doubled islet blood flow
      without affecting whole pancreatic blood flow, whereas no effect was seen after
      an equimolar dose of 3-O-methylglucose. In obese-hyperglycemic C57Bl/6 mice,
      islet blood flow was more than five times higher than in the lean C57Bl/6 mice
      when expressed as blood flow per gram pancreas. However, when islet blood
      perfusion was corrected for islet weight, it was lower in the obese than in the
      lean mice, suggesting an impaired ability in obese mice to increase blood flow in
      concert with the increased islet mass. This may contribute to the insufficient
      insulin secretion and resulting hyperglycemia seen in these animals.

PMID- 8997217
TI  - Effects of morning rise in cortisol concentration on regulation of lipolysis in
      subcutaneous adipose tissue.
AB  - Cortisol has a well-defined circadian rhythm. The aim of the study was to examine
      the effect of the morning rise in cortisol concentration on lipolysis in adipose
      tissue. Ten healthy subjects were studied on two occasions, and six of these were
      studied on three occasions. During the first two occasions, either a control or
      cortisol suppression study was performed by using metyrapone, and on the third
      occasion exogenous cortisol replacement was given in addition to metyrapone.
      Lipolysis in the subcutaneous adipose tissue of the anterior abdominal wall was
      studied by measurement of arteriovenous differences. Reduction in the early
      morning rise in cortisol led to significantly decreased venoarterialized
      differences for nonesterified fatty acids (P < 0.05) and glycerol (P < 0.01),
      attributable in part to decreased hormone-sensitive lipase (EC 3.1.1.3) action (P
      < 0.05) in adipose tissue. At the same time the arterialized plasma
      triacylglycerol concentration increased (P < 0.005) with a significant reduction
      in the adipose lipoprotein lipase (EC 3.1.1.34) rate of action (P < 0.05). In the
      replacement study, values were identical to those of the control study, showing
      that metyrapone had no nonspecific effects on lipolysis. We conclude that the
      morning rise in plasma cortisol concentration plays an important role in the
      regulation of lipolysis in adipose tissue in normal healthy adults.

PMID- 8997218
TI  - Measurement of interstitial muscle glucose and lactate concentrations during an
      oral glucose tolerance test.
AB  - To study the relationship between blood flow rate and muscle metabolism, muscle
      microdialysis was performed in nine human subjects (5 females and 4 males) after
      an oral glucose load (75 g). Two microdialysis probes were inserted into the
      medial femoral muscle for estimation of glucose and lactate concentrations in the
      interstitial fluid, and the muscle blood flow was measured concomitantly with
      strain-gauge plethysmography. After subjects fasted overnight, their glucose
      concentration in arterial plasma and interstitial fluid was 4.6 +/- 0.13 vs. 3.8
      +/- 0.23 mmol/l (P < 0.05), and the corresponding lactate concentrations were
      0.60 +/- 0.07 vs. 0.83 +/- 0.07 mmol/l (P < 0.05). Muscle blood flow was 5.2 +/-
      0.7 and 7.5 +/- 1.4 ml.100 g-1.min-1 (P < 0.05) at 0 and 90 min after oral
      glucose, respectively. The arterial-interstitial concentration differences of
      glucose increased after oral glucose [at 0 min 0.73 +/- 0.24 vs. 2.19 +/- 0.60
      mmol/l at 90 min (P < 0.001)]. The corresponding values for lactate were -0.23 +/
      0.10 at 0 min vs.-0.26 +/- 0.18 mmol/l at 90 min (not significant). The data
      show that 1) the capillary wall is partly rate limiting for glucose uptake, and
      2) after oral glucose, the glucose concentration gradient over the capillary wall
      increases despite a limited increase in blood flow rate, which then mediates
      approximately 10-20% of total enhancement of glucose uptake in muscle.

PMID- 8997220
TI  - Reversal of portacaval shunting normalizes brain energy consumption in most brain
      structures.
AB  - The cerebral metabolic rate of glucose consumption (CMRGlc) was measured
      throughout brains of rats with 1) portacaval shunts created for 2 wk, followed by
      restoration of normal blood circulation for 2 wk; 2) portacaval shunts created
      for 2 wk, followed by a sham operation and 2 wk of recovery; 3) two sham
      operations, each with 2 wk of recovery times. Portacaval-shunted rats had
      diminished CMRGlc (decreases of 7-23%) throughout the brain in agreement with
      previous studies. After restoration of normal liver blood flow, the CMRGlc of
      most structures returned to near-normal values, although a few structures,
      notably the hippocampus, remained 11-13% lower. These data suggest that the
      consequences of portacaval shunting to brain energy metabolism can be markedly
      improved, if not completely reversed, by restoring the normal pattern of blood
      flow to an otherwise healthy liver. Other metabolic and physical data collected
      (liver weight, liver-to-body weight, plasma ammonia) returned to normal except
      plasma glucose concentrations, which remained lower by 11%, suggesting a
      persistent, albeit mild, defect in glucose homeostasis.

PMID- 8997219
TI  - Islet amyloid polypeptide and insulin gene expression are regulated in parallel
      by glucose in vivo in rats.
AB  - Islet amyloid polypeptide (IAPP) is a novel amyloid-forming beta-cell hormone
      with putative roles in glucose metabolism and non-insulin-dependent diabetes
      mellitus (NIDDM) pathogenesis. To study how IAPP and insulin expression are
      regulated by glucose, rats were fasted for 48h followed by administration of
      glucose at repeated 4-h intervals; IAPP and insulin mRNA levels were determined
      by quantitative in situ hybridization. Fasting markedly reduced IAPP and insulin
      mRNA levels. Two (6 h) and four (14 h) glucose injections dose dependently
      increased both mRNA levels; the effects were matched by similar changes in plasma
      glucose levels. Actinomycin D blocked the glucose-induced increase in IAPP
      expression. IAPP and insulin mRNA levels were significantly correlated over the
      range of glucose levels. The parallel regulation of IAPP and insulin gene
      expression by glucose is consistent with a role for IAPP in glucose homeostasis.
      Thus, under hyperglycemic conditions such as NIDDM, IAPP gene expression is
      likely to increase. Hence, IAPP could, by elevated local concentrations,
      contribute to amyloid formation and/or affect metabolism unfavorably by
      inhibition of insulin release and action.

PMID- 8997221
TI  - Regulation of rat Na+/Pi cotransporter-1 gene expression: the roles of glucose
      and insulin.
AB  - Cytosolic inorganic phosphate (P(i)) is important for glucose metabolism. It
      plays a role in homeostatic regulation of glucose by insulin and glucagon.
      Recently, we isolated two cDNA clones for rat Na+/P(i) cotransporter-1 (rNaPi-1)
      and demonstrated that they are expressed primarily in the rat liver and kidney.
      We now report that the expression of rNaPi-1 in these tissues is regulated by
      fasting and streptozotocin-induced diabetes. Using rat hepatocytes in primary
      culture, we also demonstrate that glucose and insulin upregulate rNaPi-1
      expression, whereas glucagon and elevated intracellular adenosine 3',5'-cyclic
      monophosphate levels downregulate its expression. Because 2-deoxyglucose exhibits
      no effect on rNaPi-1 gene expression, we suggest that some metabolite accumulated
      during glucose metabolism may be responsible for the effects of glucose and
      insulin on rNaPi-1 gene expression. Our data also reveal that other known
      Na+/P(i) cotransporter genes, NaPi-2 and Ram-1 (a receptor for amphotropic murine
      retrovirus), are not regulated by insulin and glucose. It is therefore proposed
      that various subtypes of Na+/P(i) cotransporters are differentially regulated and
      that each subtype may be involved in a specific cellular function, rNaPi-1 may be
      responsible for Pi uptake by liver and kidney for glucose metabolism, whereas
      NaPi-2 may play a key role in P(i) reabsorption in the kidney.

PMID- 8997222
TI  - Effects and fate of human IGF-binding protein-5 in rat osteoblast cultures.
AB  - Osteoblasts prepared from calvaria of newborn rats produce insulin-like growth
      factors (IGF) and IGF-binding proteins (IGFBP), IGFBP-5 was discovered in bone
      extracts. However, we could not detect IGFBP-5 in the medium of newborn rat
      osteoblasts, although we found mRNA expression. To find an explanation for this
      discrepancy and to learn more about the physiological role of IGFBP-5 in these
      cells, we studied the biological activity and the fate of recombinant human (rh)
      IGFBP-5 in comparison to rhIGFBP-3. IGFBP-5 but not IGFBP-3 stimulated thymidine
      incorporation into DNA both in the absence and presence of IGF-I. However, IGFBP
      5 did not enhance uridine incorporation into RNA and glucose incorporation into
      glycogen. 125I-rhIGFBP-5 but not 125I-rhIGFBP-3 rapidly disappeared from the
      culture medium consistent with the observation that endogenous (rat) IGFBP-3 but
      not IGFBP-5 accumulated in the medium. However, intact 125I-labeled or unlabeled
      rhIGFBP-5 was associated with the cell-layer matrix, whereas IGFBP-5 fragments
      appeared in the medium. Trapping of IGFBP-5 in the cell layer matrix may enhance
      local availability of IGF.

PMID- 8997223
TI  - Energy expenditure in obstructive sleep apnea: effects of treatment with
      continuous positive airway pressure.
AB  - We examined 24-h energy expenditure (EE) in a chamber for indirect calorimetry in
      five male patients with obstructive sleep apnea (OSA) and six snoring control
      subjects (snorers). The 24-h EE was remeasured in patients with OSA after 3-mo
      treatment with nasal continuous positive airway pressure (CPAP). Patients with
      OSA had a greater degree of severe sleep-breathing disturbance than snorers.
      Patients with OSA had higher 24-h EE [39.2 +/- 3.0 vs. 33.9 +/- 2.7 kcal.24 h
      1.kg fat-free mass (FFM)-1, P < 0.05], daytime urinary norepinephrine and
      vanillylmandelic acid (VMA), and aminoterminal procollagen III peptide (PIIIp)
      levels, and they tended to have higher sleeping EE (32.4 +/- 4.1 vs. 26.3 +/- 1.9
      kcal.24 h-1.kg FFM-1, P < 0.1) than snorers. CPAP treatment normalized sleep
      architecture and breathing. CPAP treatment also decreased sleep EE (from 32.4 +/-
      4.1 to 27.2 +/- 1.4 kcal.24 h-1.kg FFM-1, P < 0.05) and EE variability during
      sleep (from 1.6 +/- 0.5 to 1.0 +/- 0.5 kcal.24 h-1.kg FFM-1, P < 0.05) and
      increased the basal metabolic rate-to-sleep EE ratio in all subjects. Serum PIIIp
      and plasma norepinephrine decreased after CPAP in all patients. We conclude that
      OSA is associated with an increased sleep EE, which is normalized by treatment
      with CPAP.

PMID- 8997225
TI  - Reconstitution and characterization of two forms of cyclic nucleotide-gated
      channels from skeletal muscle.
AB  - A cyclic nucleotide-gated channel present in skeletal muscle plasma membrane has
      previously been identified as being responsible for insulin-activated sodium
      entry into muscle cells (J. E. M. McGeoch and G. Guidotti. J. Biol. Chem. 267:832
      841, 1992). We have isolated this channel activity to further study and
      characterize it. The channel was solubilized from rabbit skeletal muscle
      sarcolemma and functionally reconstituted into phospholipid vesicles, as assayed
      by patch-clamp analysis of the reconstituted proteins. Channel activity was
      isolated by 8-bromo-guanosine 3',5'-cyclic monophosphate affinity chromatography,
      producing two distinct peaks of cyclic nucleotide-gated channel activity. These
      two types of channel activity differ in guanosine 3',5'-cyclic monophosphate
      affinity and in the ability to be opened by adenosine 3',5'-cyclic monophosphate.
      The cyclic nucleotide-gated channel from rod outer segments also forms two peaks
      of activity when purified in this manner. The presence of two forms of channel
      activity could have implications for the mechanism of insulin-activated sodium
      entry.

PMID- 8997224
TI  - Calcium content and respiratory control index of skeletal muscle mitochondria
      during exercise and recovery.
AB  - The purpose of this study was to evaluate the relationship between mitochondrial
      Ca2+ concentration and the respiratory control index (RCI; state III/state IV) in
      isolated mitochondria before and after exhaustive exercise at 75% of maximal O2
      consumption. Muscle biopsies of 100-150 mg from 12 moderately trained men were
      sampled at rest, immediately after exercise, and 30 or 60 min after exercise. The
      mitochondrial Ca2+ content after exhaustive exercise was significantly higher
      than the preexercise level [15.1 (range 39.4) vs. 11.6 (range 6.5) nmol/mg
      protein, respectively; P < 0.05], and RCI increased from 11.6 (range 14.4) at
      rest to 13.7 (range 15.0) at exhaustion (P < 0.05). After 60 min of recovery, the
      mitochondrial Ca2+ content was still high [18.8 (range 29.9) nmol/mg protein],
      but the RCI value was significantly depressed because of the increased state IV
      value and, in fact, was lower than the preexercise value [8.6 (range 5.1); P <
      0.05]. Our results show that the mitochondrial Ca2+ content is increased in human
      skeletal muscle after prolonged exhaustive exercise and that this is followed by
      an elevated RCI value, with slightly increased state III and decreased state IV
      respiration. The restoration of the elevated mitochondrial Ca2+ level is slow and
      could be related to an increased state IV respiration, which together indicate
      uncoupled Ca2+ respiration during recovery.

PMID- 8997226
TI  - Glutamine synthetase induction by glucocorticoids is preserved in skeletal muscle
      of aged rats.
AB  - Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key
      role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid
      induction of GS could be altered in aged rats, because alterations in the
      responsiveness of some genes to glucocorticoids were reported in aging. We
      compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal
      muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6
      8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex)
      in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and
      aged rat, respectively) for 5 days. Dex caused an increase in both GS activity
      and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged
      rats. In contrast, Dex increased GS activity in heart of adult rats, without any
      concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity
      in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is
      preserved in skeletal muscle but not in heart from aged animals.

PMID- 8997227
TI  - Effect of perfusion rate on the time course of insulin-mediated skeletal muscle
      glucose uptake.
AB  - To better define the time course of skeletal muscle glucose uptake and its
      modulation by changes in perfusion, we performed systemic euglycemic
      hyperinsulinemic clamps (40 mU.m-2.min-1) for a 90-min period in a group of lean,
      insulin-sensitive subjects (n = 9) on two occasions (approximately 4 wk apart)
      with insulin-mediated vasodilation intact or inhibited. Insulin-mediated
      vasodilation was inhibited by an intrafemoral artery infusion of NG-monomethyl-L
      arginine (L-NMMA), a specific inhibitor of nitric oxide synthase. During the
      study, leg blood flow (LBF) and arteriovenous glucose difference (AVG delta) were
      measured every 10 min; leg glucose uptake (LGU) was calculated as LGU = LBF x AVG
      delta. The systemic insulin infusion caused a time-dependent increase in LBF from
      0.194 +/- 0.024 to 0.349 +/- 0.046 l/min (P < 0.01). The intrafemoral artery
      infusion of L-NMMA completely inhibited this increase in LBF. AVG delta, LGU, and
      whole body glucose disposal rates increased in a time-dependent manner in both
      studies. The maximum AVG delta was lower with insulin-mediated vasodilation
      intact than when inhibited (25.9 +/- 2.5 vs. 35.0 +/- 1.6 mg/dl, P < 0.001). The
      time to achieve half-maximal (T1/2) AVG delta was somewhat longer with insulin
      mediated vasodilation intact compared with inhibited (35.6 +/- 4.1 vs. 29.7 +/-
      1.6 min, P < 0.01). Maximal LGU was 93.9 +/- 26.8 and 57.2 +/- 11.6 mg/min (P <
      0.005), and the T1/2 LGU was 50.2 +/- 16.0 and 36.3 +/- 8.8 min (P = 0.1) during
      intact and inhibited insulin-mediated vasodilation, respectively. Thus insulin
      mediated vasodilation has a modest effect in slowing the time course at which
      insulin stimulates glucose uptake but has a marked effect in augmenting the
      maximal rate of insulin-stimulated glucose uptake in skeletal muscle. Impaired
      insulin-mediated vasodilation, as observed in patients with essential
      hypertension, may explain, at least in part, the insulin resistance observed in
      these patients.

PMID- 8997228
TI  - Disappearance of two major phosphatidylcholines from plasma is predominantly via
      LCAT and hepatic lipase.
AB  - Metabolism of 1-stearoyl-2-arachidonyl-phosphatidyl-choline (SAPC), a major
      phosphatidylcholine (PC) species in rat plasma, was compared with 1-palmitoyl-2
      linoleoyl-PC (PLPC) metabolism. High-density lipoproteins containing SAPC and
      PLPC tracers labeled in the sn-2 fatty acid with 3H and 14C isotopes,
      respectively, were administered. The rats were depleted of endogenous bile acids
      and infused via the ileum with individual bile acids that ranged widely in
      hydrophobicity. The half-lives for SAPC and PLPC in plasma were 48 and 57 min,
      respectively. Most of the 3H activity that disappeared from plasma at 1 h was
      found in the liver in 1-palmitoyl-2-arachidonyl-PC, SAPC, and 1-oleoyl-2
      arachidonyl-PC, indicating phospholipase A1 hydrolysis of plasma SAPC forming 2
      arachidonyl-lysophosphatidylcholine, which was reacylated in the liver. Plasma
      PLPC also underwent phospholipase A1 hydrolysis, as reported previously. The
      fraction of 3H dose that accumulated in plasma cholesteryl arachidonate was two-
      to threefold higher than the fraction of 14C dose in cholesteryl linoleate.
      Multicompartmental models for SAPC and PLPC were developed that included
      lysophosphatidylcholines and cholesteryl esters. Bile acids did not influence
      plasma PC metabolism. Lecithin-cholesterol acyltransferase and phospholipase A1
      (hepatic lipase) hydrolysis accounted for > or = 90% of the SAPC and PLPC that
      disappeared from plasma; SAPC and PLPC are comparable as substrates for hepatic
      lipase, but SAPC is preferred by lecithin-cholesterol acyltransferase.

PMID- 8997230
TI  - Diurnal rhythms and effects of fasting and refeeding on rat adipose tissue
      lipoprotein lipase.
AB  - The activity of lipoprotein lipase (LPL) in adipose tissue is modulated by
      changes in the nutritional status. We have measured LPL activity, mass, and mRNA
      levels in rat adipose tissue during normal feeding cycles, during short- and long
      term fasting, and during refeeding after fasting. LPL activity displayed a
      diurnal rhythm. The activity was highest during the night and early morning,
      decreased to a minimum during the early afternoon, and then increased again.
      These changes corresponded to the feeding pattern. The increases and/or decreases
      resulted from changes in LPL synthetic rate compounded by posttranslational
      mechanisms. During short-term fasting, LPL specific activity decreased to < 30%
      of control. The specific activity was restored within 4 h by refeeding. On longer
      fasting, LPL mRNA decreased. This became significant from 36 h. On refeeding, it
      took 12 h to restore the mRNA levels, whereas tissue LPL activity and mass could
      not be fully restored by 36 h of refeeding. These data show that LPL activity
      during short-term fasting is regulated posttranscriptionally, which allows for
      quick upregulation after refeeding. On longer fasting, other mechanisms affecting
      LPL transcription and synthesis come into play, and upregulation after refeeding
      is slowed down.

PMID- 8997229
TI  - Acute postprandial changes in leucine metabolism as assessed with an
      intrinsically labeled milk protein.
AB  - Mechanisms of protein gain during protein feeding have been investigated using a
      combination of oral and intravenous labeled leucine in healthy young men. The
      oral labeled leucine was administered as a free oral tracer ([13C]- or
      [2H3]leucine) added to unlabeled whey protein or as whey protein intrinsically
      labeled with L-[1-13C]leucine. When the oral tracer was free leucine, it appeared
      in the plasma more rapidly than the unlabeled leucine derived from the whey
      protein, and this resulted in an artifactual 88% decrease of protein breakdown.
      When the oral tracer was protein bound, protein breakdown did not change
      significantly after the meal. In contrast, nonoxidative leucine disposal (i.e.,
      protein synthesis) was stimulated by 63% by the meal. In conclusion, 1) an
      intrinsically labeled protein is more appropriate than an oral free tracer to
      study postprandial leucine kinetics under non-steady-state conditions and 2)
      protein gain after a single whey protein meal results solely from an increased
      protein synthesis with no modification of protein breakdown.

PMID- 8997231
TI  - Quantitative aspects of interorgan relationships among arginine and citrulline
      metabolism.
AB  - The quantitative roles of the splanchnic region and the kidneys in whole body
      (WB) arginine and citrulline metabolism were assessed in postabsorptive mongrel
      dogs with primed constant intravenous infusions of [15N2-guanidino, 5,5
      2H2]arginine and [13C-ureido]citrulline or [13C-guanidino]arginine and [15N]urea
      tracers. Isotope and metabolite concentration balances of arginine and citrulline
      were measured across the gut, liver, splanchnic region, and kidneys, together
      with WB arginine and citrulline fluxes and urea production rate. The WB
      citrulline flux and rate of citrulline to arginine (C-A) conversion were 16 and
      9.4 mumol.kg-1.h-1, respectively. Concentration balance of citrulline across
      kidneys was +8.2 mumol.kg-1.h-1, and metabolism of citrulline by kidneys was 8.7
      mumol.kg-1.h-1, which was derived about equally from intestine and liver. The
      appearance rate of citrulline-derived arginine in renal vein was 6.8 mumol.kg-1.h
      1. These three separate estimates of C-A conversion within the kidneys were in
      good agreement, indicating 40% of blood C-A conversion occurring outside kidneys.
      These findings of interorgan metabolism are discussed in reference to the current
      knowledge derived largely from studies in laboratory rodents.

PMID- 8997232
TI  - Glycerol production and utilization in humans: sites and quantitation.
AB  - Liver is assumed to be the major site of glycerol uptake and fatty acid
      reesterification. [U-13C]glycerol was infused into ten 60 h-fasted healthy
      subjects. Measured were 1) blood glycerol concentrations and 13C enrichments in
      brachial and pulmonary arteries and in hepatic, renal, superficial, and deep
      forearm veins; 2) glycerol appearance rates in systemic circulation; and 3)
      splanchnic bed and kidney glycerol uptakes with use of balance and tracer
      methodology. Glycerol concentrations were one-fifth in hepatic, one-half in
      renal, 40% more in superficial, and the same in deep vein and pulmonary artery as
      in brachial artery blood. Glycerol enrichments were one-fifth in hepatic, two
      thirds to three-quarters in renal and superficial veins, and the same in
      pulmonary as in brachial artery blood. Splanchnic glycerol uptake was 29% and
      kidney glycerol uptake was 17% of glycerol's rate of appearance, 5.11 mumol.min
      1.kg-1. Splanchnic fatty acid uptake was 25% of calculated fatty acid release.
      Glycerol contributed 15% to glucose production. Most of the [13C]glycerol uptake
      by splanchnic bed and kidneys was incorporated into glucose. Thus, in 60 h-fasted
      individuals, most glycerol uptake does not occur in liver, and the extent of
      fatty acid reesterification in liver is in doubt.

PMID- 8997233
TI  - Contributions of liver and kidneys to glycerol production and utilization in the
      dog.
AB  - The classical concept holds that liver and kidneys are the main sinks of glycerol
      released by adipose tissue. However, rates of glycerol appearance (Ra) exceed the
      rate of glycerol delivery to liver and kidneys. We measured the hepatic and renal
      contributions to glycerol production and utilization in anesthetized dogs that
      were fasted either overnight or for 24 h after 3 days on a carbohydrate-free
      diet. Dogs were infused with [2H5]glycerol, and the concentration and 2H
      enrichment of glycerol were measured across liver and kidney. After a baseline
      period, either norepinephrine or glucose plus insulin was infused to alter the
      rate of glycerol production. Our study shows that the production of glycerol by
      liver and kidneys amounted to 4-9% and 4-7% of the Ra of glycerol, respectively.
      Uptake of glycerol by liver and kidneys amounted to 26-30 and 10-19% of the Ra of
      glycerol, respectively. Thus, contrary to the classical concept, the bulk of
      glycerol utilization occurs in nonhepatic, nonrenal tissues that have very low
      glycerol kinase activity per gram.

PMID- 8997234
TI  - Glucose-6-phosphatase flux and the hepatic glucose balance model.
AB  - Mice were studied with the euglycemic hyperinsulinemic and the hyperglycemic
      clamp techniques after a 6-h fast: 1) euglycemic (6.7 +/- 0.2 mM)
      hyperinsulinemia (approximately 800 microU/ml); 2) hyperglycemic (15.3 +/- 0.4
      mM) hyperinsulinemia (approximately 800 microU/ml). All mice received an infusion
      of [3-3H]glucose and [U-14C]lactate. Basal hepatic glucose production (HGP)
      averaged approximately 170 mumol.kg-1.min-1 in both groups. During euglycemic and
      hyperglycemic hyperinsulinemia, HGP decreased by 53% (to 76.7 +/- 11.1 mumol.kg
      1.min-1; P < 0.01) and 74% (to 43.3 +/- 7.2 mumol.kg-1.min-1; P < 0.01),
      respectively. Hyperglycemia increased glucose cycling (by 2.1-fold; P < 0.01) and
      the contribution of gluconeogenesis to HGP (88 vs. 43%; P < 0.01) while
      decreasing that of glycogenolysis (12 vs. 57%; P < 0.01). The percentage of
      neosynthetized hepatic glycogen formed via the direct pathway was markedly
      increased during hyperglycemia (53 +/- 2% vs. 23 +/- 3%; P < 0.01). These data
      indicate that the assessment of hepatic glucose fluxes can be accomplished in
      conscious unrestrained mice and that, in the presence of hyperinsulinemia,
      hyperglycemia causes 1) a further inhibition of HGP mainly via inhibition of
      glycogenolysis and increase in hepatic glucose cycling; and 2) about a fivefold
      stimulation in the direct pathway of hepatic glycogen formation.

PMID- 8997235
TI  - Altered muscle insulin sensitivity in the male offspring of protein-malnourished
      rats.
AB  - Insulin sensitivity of skeletal muscle was studied in male offspring of rat dams
      fed either a 20% (control) or 8% (low-protein) diet during pregnancy and
      lactation. Freshly isolated muscle strips took up more [3H]methylglucose from low
      protein animals than from controls (19.2 +/- 2.5 and 4.26 +/- 0.45 nmol.min-1.mg
      muscle-1, respectively, P < 0.001). However, after a 60-min preincubation there
      was no significant difference in basal glucose transport (4.02 +/- 0.42 and 4.23
      +/- 0.35 nmol.min-1.mg-1 for control and low-protein animals, respectively).
      Insulin (300 pM) had a significantly greater (P < 0.001) effect on stimulation of
      glucose transport into preincubated low-protein muscle strips than into controls
      (to 14.14 +/- 1.25 and 9.61 +/- 0.71 nmol.min-1.mg-1, respectively). There were
      no differences in total GLUT-4 protein content. However, subcellular
      fractionation revealed significantly (P < 0.001) more GLUT-4 in muscle plasma
      membranes of low-protein animals compared with controls. Insulin increased (P <
      0.001) the GLUT-4 content of control plasma membranes but had no effect in low
      protein animals. There were twofold more insulin receptors in low-protein muscle
      membranes compared with controls (2.35 +/- 0.17 x 10(11) and 1.28 +/- 0.10 x
      10(11) and insulin receptors/mg muscle membrane protein, respectively, P < 0.01).
      These results suggest that programming of muscle insulin sensitivity can occur
      during fetal life.

PMID- 8997236
TI  - Esophageal sensation in spinal cord-injured patients: balloon distension and
      cerebral evoked potential recording.
AB  - We sought to determine the esophageal sensory function in patients with a C6 or
      C7 spinal cord injury. A balloon was repetitively distended 10 cm above the lower
      esophageal sphincter in five patients and nine normal control subjects. Sensation
      was reported on a scale from 0 to 2 with progressive distension to pain threshold
      (level 2). Cortical responses were recorded from midline scalp electrodes.
      Blinded determinations of quality and reproducibility of the potentials were
      performed. All subjects experienced sensation with esophageal balloon distension.
      Volumes to sensation showed a trend toward a higher sensory threshold in patients
      but were significant only for first sensation, not pain. In all subjects, a
      triphasic evoked potential response consisting of a negative-positive-negative
      complex was noted with distension but not with sham distension. Characteristics
      (amplitude, latency, reproducibility, and quality) of the evoked potentials were
      not different in patient and control groups. These data suggest sensory pathways
      from the distal esophagus are intact in patients with a C6 or C7 spinal cord
      injury.

PMID- 8997237
TI  - Fos is required for EGF stimulation of the gastrin promoter.
AB  - Gastrin gene expression is regulated by developmental cues, pH, and inflammation.
      These processes are mediated by various extracellular ligands, e.g., growth
      factors, cytokines, and neuropeptides that also stimulate c-fos gene expression.
      Therefore, to determine whether Fos is required for stimulation of the gastrin
      promoter, a c-fos sense expression vector was coexpressed with a gastrin reporter
      construct in a GH4 rat pituitary cell line. We found that epidermal growth factor
      (EGF) and tumor necrosis factor-alpha (TNF-alpha) transiently stimulate an
      increase in Fos protein that precedes stimulation of the gastrin promoter.
      However, the induction mediated by TNF-alpha was weaker than that mediated by
      EGF, indicating minimal overlap of the signaling pathways activated by EGF and
      TNF-alpha. Accordingly, overexpression of c-fos mRNA facilitated primarily EGF
      rather than TNF-alpha induction of the gastrin promoter. Expression of the c-fos
      gene in the absence of ligand did not stimulate the gastrin promoter. Thus c-fos
      gene expression is required but is not sufficient for induction of the gastrin
      promoter by EGF.

PMID- 8997238
TI  - Involvement of ICE family proteases in apoptosis induced by reoxygenation of
      hypoxic hepatocytes.
AB  - Cell death due to reoxygenation after hypoxia was characterized in primary
      cultured hepatocytes. Fluorescence and electron microscopic analyses of
      reoxygenated hepatocytes revealed morphological characteristics of apoptosis,
      including chromatin condensation, nuclear fragmentation, and formation of
      apoptotic bodies. Few necrotic hepatocytes, defined by loss of plasma membrane
      integrity, mitochondrial swelling, and formation of large vacuoles, were
      observed. Activation of interleukin-1 beta-converting enzyme (ICE)-like and
      CPP32/Yama-like proteases, which are known to drive apoptosis, was observed
      during reoxygenation, and addition of their respective inhibitors inhibited the
      induction of apoptosis, indicating the involvement of ICE family proteases in
      apoptosis by reoxygenation. Production of oxygen radicals was enhanced by
      reoxygenation of hypoxic cells, and reoxygenation-induced apoptosis was inhibited
      by oxygen radical scavengers, suggesting a role for reactive oxygen species as a
      triggering factor in cell death. Electrophoretic analysis revealed the presence
      of 50-kb DNA fragments but not oligonucleosomal DNA fragments in reoxygenation
      induced apoptotic hepatocytes.

PMID- 8997239
TI  - Structure, glycosylation, and localization of rat intestinal guanylyl cyclase C:
      modulation by fasting.
AB  - Guanylyl cyclase C (GC-C), an intestinal receptor guanylyl cyclase, binds
      diarrhea-producing bacterial ligands such as the Escherichia coli heat stable
      enterotoxin. We examined the regulatory influence of feeding and fasting on the
      expression, structure, and biochemical properties of GC-C. When solubilized at 4
      degrees C under nonreducing conditions, GC-C from both fed and fasted rats
      migrated on 7% sodium dodecyl sulfate-polyacrylamide electrophoretic gels as two
      extremely large aggregates that barely penetrated the stacking and resolving
      gels. Chemical reduction of disulfide linkages disaggregated GC-C in fed but not
      fasted rat samples, causing it to migrate as smaller forms (approximately 220 and
      240 kDa). Although GC-C aggregates from fasted rats resisted this disaggregating
      effect of chemical reduction, they rapidly acquired it within 90 min of
      refeeding. When solubilized at denaturing temperatures (95 degrees C) under
      reducing conditions, GC-C aggregates largely disassembled into four smaller
      proteins (relative molecular weight approximately 140,000, 131,000, 85,000, and
      65,000). However, the 131-kDa glycoprotein was disproportionately increased in
      fasted rat membranes. This unit and the 220-kDa unit were sensitive to
      endoglycosidase H. Subcellular fractionation and immunohistochemical studies
      revealed a major redistribution of GC-C from surface to intracellular enterocyte
      sites during fasting.

PMID- 8997240
TI  - Simultaneous manipulation of intestinal capacities and nutrient loads in mice.
AB  - To study the relationship between capacity and load in the small intestine, we
      simultaneously varied dietary nutrient load and intestinal capacity in mice.
      Intestinal transection alone caused an increase in intestinal mass, because of
      increased serosal mass. Because virgin mouse intestine possesses 180% reserve
      uptake capacity before resection and the intestine regenerates after resection,
      resection of up to 50% had no effect on food intake, digestive efficiency,
      intestinal brush-border glucose uptake rate, or mass of all organs measured
      except the cecum. Regeneration of intestinal mass and glucose uptake capacity was
      quantitatively complete, because intestinal mass 10 wk after resection was
      similar to that in unresected mice. Resected intestinal mass in lactating mice
      was four times larger than that immediately after resection in virgin mice. Cecal
      mass increased in 50%-resected lactating mice with high food intakes, suggesting
      nutrient spillage into the distal gut as a signal for regeneration. Mice failed
      to survive 70% resection of the intestine, possibly because intestinal reserve
      uptake capacity was exhausted immediately after surgery, making regeneration
      impossible.

PMID- 8997241
TI  - Tumor necrosis factor unresponsiveness after surgery in bile duct-ligated rats.
AB  - In obstructive jaundice, postoperative complications are related to gut-derived
      endotoxemia and possibly mediated by cytokines such as tumor necrosis factor
      (TNF) and interleukin-6 (IL-6). This study investigated the course of IL-6 and
      TNF after surgery in bile duct-ligated rats (BDL) treated with and without an
      enteral endotoxin binder (cholestyramine). Endotoxin in rat plasma was determined
      by blocking cytokine production in whole blood cell cultures stimulated by rat
      plasma using antibodies directed against the endotoxin (CD14) receptor. Surgery
      elicited a significant IL-6 response in saline-treated BDL rats (BDL-SAL). TNF,
      however, remained at its low preoperative levels. Cholestyramine treatment
      resulted in undetectable preoperative TNF and IL-6 levels, but levels of both
      cytokines were significantly raised after surgery. Endotoxin, as determined by
      the CD14 blockade test, was identified in the BDL-SAL group, before (time 0) and
      after surgery (2 and 4 h), whereas in the cholestyramine group endotoxin was only
      present at 2 h after surgery. The lack of a postoperative plasma TNF response in
      the BDL-SAL group in the continuous presence of endotoxin suggests endotoxin
      tolerance for TNF production in obstructive jaundice.

PMID- 8997242
TI  - Effects of neuropeptide Y and substance P on antigen-induced ion secretion in rat
      jejunum.
AB  - We previously described a model of intestinal hypersensitivity in which isolated
      gut segments from sensitized rats demonstrated a rapid epithelial secretory
      response to luminal antigen that was mediated by mucosal mast cells and capsaicin
      sensitive nerves. In this study, we examined the ability of the inhibitory
      neuropeptide, neuropeptide Y (NPY), to diminish the antigen-induced secretory
      response. Rats were sensitized to egg albumin (EA), and 12-14 days later, jejunal
      tissue was excised and mounted in Ussing chambers. NPY inhibited the short
      circuit current (Isc) increase and Cl- secretion evoked by addition of EA to the
      luminal side of the tissue; neural blockade with tetrodotoxin (TTX) had a similar
      inhibitory effect. In contrast, NPY was much less effective, and TTX was
      completely ineffective, on the response to serosal antigen. Additional
      experiments examined the cell target for NPY action. NPY and TTX almost abolished
      the Isc response to electrical transmural stimulation of enteric nerves,
      suggesting a possible neural site of action. In addition, NPY significantly
      reduced baseline Isc; this inhibition involved both TTX-dependent and TTX
      independent components. Because nerves were previously shown to facilitate
      antigen uptake and substance P was implicated in the response to only luminal
      antigen, we postulated that NPY was inhibiting nerves that facilitate antigen
      transport from the lumen to effector cells in the lamina propria. We therefore
      examined the effect of exogenous substance P added after NPY inhibition.
      Substance P restored the luminal antigen-induced secretory response to
      pretreatment values. We conclude that the neuropeptides play a significant role
      in immunophysiology by acting at neural and epithelial sites in the intestinal
      mucosa.

PMID- 8997243
TI  - HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and
      pancreatic cells.
AB  - Human hepatocarcinoma-intestine-pancreas (HIP) cDNA, isolated from a
      hepatocellular carcinoma, encodes a C-type lectin. According to published cDNA
      sequences, HIP protein is identical to human pancreatitis-associated protein
      (PAP). In these sequences, a putative signal peptide and the carbohydrate
      recognition domain (CRD) can be recognized. In the present study, we established
      transgenic mice to drive the production of soluble recombinant HIP/PAP protein in
      the milk of lactating animals; using this model, we showed that HIP/PAP protein
      was secreted after suitable cleavage of the potential signal peptide. Moreover,
      we also produced HIP/PAP protein by Escherichia coli cultures performed to
      generate specific antibodies. These antibodies enabled the detection of HIP/PAP
      protein in normal intestine and pancreas (both in endocrine and exocrine cells),
      e.g., intestinal neuroendocrine and Paneth cells, pancreatic islets of
      Langerhans, and acinar cells. HIP/PAP protein was also identified in the
      cytoplasm of tumoral hepatocytes but not in nontumoral hepatocytes. Finally,
      HIP/PAP protein activity was tested and we showed that HIP/PAP induced the
      adhesion of rat hepatocytes and bound strongly to extracellular matrix proteins
      (laminin-1, fibronectin), less strongly to type I and IV collagen, and not at all
      to heparan sulfate proteoglycan. In conclusion, these results showed that HIP/PAP
      protein was matured on secretion. We also demonstrated that HIP/PAP protein was
      specifically expressed in hepatocarcinoma cells and interacted with rat
      hepatocytes and the extracellular matrix. Taken overall, these results suggest
      that HIP/PAP protein may be of potential importance to liver cell
      differentiation/proliferation.

PMID- 8997245
TI  - Tachykinin-induced increase in gastric mucosal resistance: role of primary
      afferent neurons, CGRP, and NO.
AB  - The tachykinins [Ala5,beta-Ala8]neurokinin A-(4-10) {[Ala5,beta-Ala8]NKA-(4-10)}
      and NKA-(4-10) dose dependently protected against ethanol-induced gastric mucosal
      damage in rats (half-maximal inhibitory dose, 46 and 48 nmol/kg, respectively).
      These effects were abolished by primary afferent nerve denervation, calcitonin
      gene-related peptide (CGRP) immunoneutralization, the CGRP receptor antagonist
      human (h) hCGRP-(8-37), and inhibition of nitric oxide (NO) biosynthesis by NG
      nitro-L-arginine methyl ester. Tachykinin-induced protection occurred despite
      marked depression of gastric mucosal blood flow and was not associated with
      increased acid secretion. NK2-receptor blockade antagonized the protective
      effects of [Ala5,beta-Ala8]NKA-(4-10) and NKA-(4-10), whereas NK1-receptor
      blockade was ineffective. Blockade of NK2 but not NK1 receptors prevented by 65%
      the protection evoked by topical capsaicin without affecting capsaicin-induced
      hyperemia. We conclude that the increase in gastric mucosal resistance evoked by
      tachykinins is NK2 receptor-mediated and involves primary afferent neurons, CGRP,
      and NO. Gastric mucosal hyperemia and increased acid secretion do not participate
      in the effect. Tachykinins activating NK2 receptors contribute to the increase in
      gastric mucosal resistance but not the increment in mucosal blood flow after
      primary afferent nerve stimulation by capsaicin.

PMID- 8997244
TI  - Electrophysiological characterization of a motilin agonist, GM611, on rabbit
      duodenal smooth muscle.
AB  - Effects of motilin and a newly synthesized erythromycin derivative, GM611, on
      membrane potential and currents of rabbit duodenal smooth muscle have been
      investigated by intracellular potential recording and whole cell patch-clamp
      technique and compared with results from contractile experiments. Motilin and
      GM611 (0.01-100 nM) dose dependently produced slowly sustained depolarizations
      (half-maximal effective dose = 0.15 and 3.9 nM for motilin and GM611,
      respectively) but exhibited biphasic effects on spike activities superimposed on
      slow waves. With small depolarizations, the number of spike discharges increased,
      whereas larger depolarizations markedly reduced spike amplitude. Motilin-induced
      (or GM611-induced) depolarization appeared to be associated with the activation
      of monovalent cation-selective channels, and the reduction in the spike amplitude
      appeared mainly to be associated with inhibition of voltage-dependent Ca2+
      channels. Furthermore, data from patch-clamp experiments suggested that Ca2+
      release occurred from heparin-sensitive internal stores upon stimulation of
      motilin receptors by these agonists. Possible implications of these
      electrophysiological effects in motilin- or GM611-induced tonic and phasic
      contractions have been discussed.

PMID- 8997246
TI  - Adenosine A2-receptor mediates ethanol-induced arteriolar dilation in rat
      stomach.
AB  - Topical application of ethanol to the gastrointestinal mucosa induces
      vasodilation. Using an in vivo microscopy technique, we studied the effect of
      topical ethanol on the submucosal microvessels that control mucosal blood flow in
      the rat stomach and identified vasoactive substances and receptors that mediate
      the ethanol vasoaction. Topical ethanol (1-20%) dilated submucosal arterioles
      dose dependently, but did not change venular diameters. An inhibitor of alcohol
      dehydrogenase, 1 mM 4-methylpyrazole, did not alter the ethanol vasoaction.
      Ethanol-induced arteriolar dilation was eliminated by adenosine deaminase, but
      other vasodilator inhibitors such as atropine, pyrilamine, indomethacin, human
      calcitonin gene-related peptide-(8-37), and N omega-nitro-L-arginine methyl ester
      did not prevent it. Ethanol-induced arteriolar dilation was inhibited by an
      adenosine A2-receptor antagonist, but not by an A1-receptor antagonist, whereas
      an A2-agonist, but not an A1-agonist, dose dependently dilated arterioles.
      Exogenous adenosine (10(-5)-10(-3) M) dilated arterioles to a similar extent as
      ethanol. This response was inhibited by an A2-antagonist. We conclude that
      nonmetabolized ethanol increases gastric mucosal blood flow via A2-receptors in
      submucosal arterioles.

PMID- 8997247
TI  - Effects of potassium on magnesium transport across rumen epithelium.
AB  - Increasing ruminal K concentration impairs active Mg transport across the
      forestomach epithelium of ruminants. We used Ussing chamber and microelectrode
      techniques to test the hypothesis that high mucosal K decreases the driving force
      for Mg2+ uptake by depolarizing the apical membrane. Serosal Ba enhanced net 42K
      secretion. Under open-circuit conditions, rumen epithelial cells showed an apical
      membrane potential (Va) of -67.3 +/- 1.5 mV. An increase in mucosal K
      concentration depolarized Va and decreased mucosal-to-serosal 28 Mg flux (Jm-
      >sMg). An increase in the transepithelial potential difference (Vt) depolarized
      Va, greatly decreased Jm-->sMg, and slightly increased Mg serosal-to-mucosal flux
      (Js-->mMg). Jm-->sMg exhibited an electrogenic and an electroneutral component.
      Mucosal verapamil depolarized Va and reduced Jm-->sMg, without affecting Js-
      >mMg. The study shows that rumen epithelial cells exhibit apical and basolateral
      K conductances and that transcellular Mg absorption has a distinct electrogenic
      component. This supports the assumption that a change in Va represents the link
      between increased ruminal K concentration and decreased Mg absorption. The
      results are discussed with regard to the development of hypomagnesemia in
      ruminants.

PMID- 8997248
TI  - Continuous measurement of gastric nitric oxide production.
AB  - With the use of a double-lumen catheter, nitric oxide (NO) was dialyzed across a
      Gore-Tex membrane into a gas phase and subsequently analyzed on-line by
      chemiluminescence. This new technique for the continuous measurement of NO was
      evaluated bench-side and applied in the human stomach in vivo to measure the
      nonenzymatic formation of NO generated from nitrite in an acidic milieu. A linear
      relation (r2 = 0.991, P < 0.0001) between concentrations of NO in aqueous
      solutions (2.5-52.5 mM) and NO in the corresponding gas phases obtained by the
      dialysis technique (50-1,000 parts per billion) validated the present method for
      quantitative analyses of NO. Interassay and intra-assay coefficients of variation
      at all concentrations of NO for six experiments were < 5%. High intragastric
      concentrations of NO (in the micromolar range) were found during basal
      conditions. The requirement of both nitrite from the saliva and an acidic
      environment for NO formation is indicated, since depletion of saliva as well as
      acid neutralization greatly reduced gastric NO concentrations. Furthermore, large
      amounts of gastric NO were formed after intake of sodium nitrate. With the use of
      this technique, NO can be continuously measured with accuracy experimentally and
      clinically in any organ accessible to intubation.

PMID- 8997249
TI  - Ethinyl estradiol cholestasis involves alterations in expression of liver
      sinusoidal transporters.
AB  - The mechanisms involved in ethinyl estradiol-induced cholestasis are
      controversial. Basal bile flow was reduced by ethinyl estradiol administration,
      with a half time (t1/2) of 12.5 +/- 0.6 h. In contrast, initial taurocholate
      uptake was not significantly reduced until 3 days to 59% of control and to 13 and
      10% of control at 5 and 7 days, respectively. The t1/2 was 4.3 +/- 0.1 days.
      These physiological changes were correlated with measurement of protein mass and
      steady-state mRNA for Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase),
      Na(+)-dependent taurocholate transporter, organic anion transporters, and
      membrane lipid fluidity. Ethinyl estradiol significantly decreased Na(+)-K(+)
      ATPase activity and membrane fluidity. However, neither Na(+)-K(+)-ATPase alpha
      subunit nor beta-subunit mass was altered by ethinyl estradiol administration. In
      contrast, protein content of the Na(+)-dependent taurocholate transporter was
      significantly reduced to 21% of control (P < 0.001) at 5 days. The Na(+)
      dependent taurocholate transporter was identified in sinusoidal membrane
      fractions as a doublet with a molecular size estimated to be 51 and 56 kDa.
      Although both bands were reduced with ethinyl estradiol treatment, the 56-kDa
      band was decreased more rapidly and to a greater extent than the 51-kDa band. The
      estimated t1/2 of 4.8 +/- 0.6 days for the doublet was similar to that for Na(+)
      dependent taurocholate uptake. The organic anion transporter protein mass was
      similarly reduced with time of ethinyl estradiol administration to 21% of control
      (P < 0.01) at 5 days. Ethinyl estradiol also rapidly decreased the steady-state
      mRNA levels of Na(+)-dependent and organic anion transporters to approximately
      50% and 15% of control at 5 days, respectively. These studies indicate early
      generalized abnormalities of the sinusoidal membrane lipid fluidity, Na(+)-K(+)
      ATPase activity, and bile acid transport protein content.

PMID- 8997250
TI  - Ca2+ role in myogenic and neurogenic activities of canine ileum circular muscle.
AB  - The role of Ca2+ in myogenic and neural activation in canine ileum circular
      muscle (CM) was studied during simultaneous recordings of contractile and
      electrical activity in cross-sectioned slabs of muscularis externa or of isolated
      CM with deep muscular plexus (DMP) intact. Ca(2+)-free Krebs solution abolished
      inhibitory junction potentials (IJP) and contractions before changes in CM
      membrane potentials and while slow waves (SW) persisted at lower amplitude and
      frequency. This medium abolished SW more rapidly in isolated CM than in intact
      muscle strips and affected triggered SW (TSW) by 100-ms pulses recorded near
      myenteric plexus or near DMP differentially in the full-thickness preparation;
      TSW did not occur in isolated CM. Ni2+, a nonselective Ca2+ channel antagonist,
      left IJP unchanged and reduced contractions, frequencies, and amplitudes of
      spontaneous SW and TSW, but increased their durations. Nifedipine abolished
      contractions but SW, TSW, and IJP were unaffected. Cyclopiazonic acid (CPA)
      increased SW frequency, produced spikes on SW plateaus, and increased CM tone,
      but did not affect IJP or resting membrane potentials. In nifedipine-pretreated
      strips, CPA decreased SW frequencies and amplitudes, evoked less tone,
      depolarized membrane potentials, and left IJP unaltered. The neuronal N-type Ca2+
      channel blocker omega-conotoxin GVIA abolished IJP, without affecting SW or TSW.
      We conclude that Ca2+ influx, not through L- or N-type Ca2+ channels, helps
      initiate ileal SW; L-type Ca2+ channels provide Ca2+ for contraction and N-type
      Ca2+ channels provide Ca2+ for IJP mediator release. Frequencies of SW may be
      modulated by uptake of Ca2+ into pacemaker stores.

PMID- 8997251
TI  - Effect of surface and intracellular pH on hepatocellular fatty acid uptake.
AB  - Fatty acids enter hepatocytes, at least in part, by a carrier-mediated uptake
      mechanism. The importance of driving forces for fatty acid uptake is still
      controversial. To evaluate possible driving mechanisms for fatty acid transport
      across plasma membranes, we examined the role of transmembrane proton gradients
      on fatty acid influx in primary cultured rat hepatocytes. After hepatocytes were
      loaded with SNARF-1 acetoxymethyl ester, changes in intracellular pH (pHi) under
      different experimental conditions were measured and recorded by confocal laser
      scanning microscopy. Fatty acid transport was increased by 45% during cellular
      alkalosis, achieved by adding 20 mM NH4Cl to the medium, and a concomitant
      paracellular acidification was observed. Fatty acid uptake was decreased by 30%
      during cellular acidosis after withdrawal of NH4Cl from the medium. Cellular
      acidosis activates the Na+/H+ antiporter to export excessive protons to the outer
      cell surface. Inhibition of Na+/H+ antiporter activity by amiloride diminishes
      pHi recovery and thereby accumulation of protons at the outer surface of the
      plasma membrane. Under these conditions, fatty acid uptake was further inhibited
      by 57% of control conditions. This suggests stimulation of fatty acid influx by
      an inwardly directed proton gradient. The accelerating effect of protons at the
      outer surface of the plasma membrane was confirmed by studies in which pH of the
      medium was varied at constant pHi. Significantly higher fatty acid influx rates
      were observed at low buffer pH. Recorded differences in fatty acid uptake
      appeared to be independent of changes in membrane potential, because BaCl2 did
      not influence initial uptake velocity during cellular alkalosis and paracellular
      acidosis. Moreover, addition of oleate-albumin mixtures to the NH4Cl incubation
      buffer did not change the observed intracellular alkalinization. In contrast,
      after cells were acid loaded, addition of oleate-albumin solutions to the
      recovery buffer increased pHi recovery rates from 0.21 +/- 0.02 to 0.36 +/- 0.05
      pH units/min (P < 0.05), indicating that fatty acids further stimulate Na+/H+
      antiporter activity during pHi recovery from an acid load. It is concluded that
      carrier-mediated uptake of fatty acids in hepatocytes follows an inwardly
      directed transmembrane proton gradient and is stimulated by the presence of H+ at
      the outer surface of the plasma membrane.

PMID- 8997252
TI  - CFTR expression and mucin secretion in cultured mouse gallbladder epithelial
      cells.
AB  - Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in
      humans is frequently associated with progressive liver disease, which appears to
      result from obstruction of biliary ducts with mucous material. CFTR in the liver
      is expressed in the biliary epithelium. With the use of a mouse model for cystic
      fibrosis (CF) we have studied the relationship between CFTR expression and
      glycoprotein secretion in primary culture of mouse gallbladder epithelial cells
      (MGBC) MGBC in culture maintain a well-differentiated phenotype as shown by
      microscopy. The cells produce CFTR mRNA to levels comparable to the intact
      tissue. With patch-clamp analysis we could frequently observe a linear protein
      kinase A-regulated Cl- channel that shows all the major characteristics of human
      CFTR, although its conductance is lower (5 pS compared with 8 pS). MGBC in
      culture produce and secrete high molecular weight glycoproteins (HMG) in a time
      dependent and temperature-sensitive manner. Secretion of HMG was not stimulated
      significantly by either adenosine 3',5'-cyclic monophosphate (cAMP), Ca2+, or
      protein kinase C agonists in this system. High concentrations (3 mM) of
      extracellular ATP stimulated secretion threefold, but low concentrations (0.3 mM)
      had no effect. Approximately one-third of the HMG produced and secreted consisted
      of mucin. Cultured MGBC from CFTR-deficient mice produced and secreted mucin to a
      similar extent as normal cells. We conclude that cultured mouse gallbladder cells
      are a convenient model to study both CFTR function and mucin secretion. In this
      system, we found no evidence for a direct link between mucin secretion and CFTR
      activity, as has been suggested for other cell types.

PMID- 8997253
TI  - Regulation of taurocholate and ursodeoxycholate uptake in hamster hepatocytes by
      Ca(2+)-mobilizing agents.
AB  - In isolated hamster hepatocytes, the Ca2+ ionophore A-23187 immediately decreased
      the uptake rate of taurocholic acid (TCA) by 60-70%, whereas it slowly inhibited
      that of ursodeoxycholic acid (UDCA) by a maximum of 35-45%, with an inhibition
      constant (Ki) of 0.36 and 1.93 microM, respectively. In contrast to ionomycin,
      which mimicked the effect of A-23187, vasopressin inhibited the bile acid uptake
      rate by 40 and 45%, respectively, only after a 5- to 10-min preincubation. The
      Na(+)-dependent bile acid transport was exclusively inhibited by these agents,
      and this inhibition was independent of extracellular Ca2+. However, intracellular
      Ca2+ depletion with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid or chelation with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid resulted in 40-50% inhibition of the uptake rate of both bile
      acids. The exogenous protein kinase C activator, phorbol 12-myristate 13-acetate
      (PMA), but not the nonactive 4 alpha-phorbol, significantly inhibited TCA uptake
      rate. Although both A-23187 and ionomycin immediately increased and decreased the
      cellular Na+ and K+ concentration, respectively, neither vasopressin nor PMA had
      a significant effect on the cellular concentration of these cations, even after a
      10-min incubation. Furthermore, the effect of A-23187 and ionomycin on TCA uptake
      and Na+ flux, respectively, disappeared after a 40-min preincubation, and
      additional ionophore remained without effect. However, after a 40-min incubation
      with A-23187, PMA was still able to inhibit TCA uptake. Therefore, A-23187 and
      ionomycin transiently inhibited Na(+)-dependent uptake of both TCA and UDCA, in
      part because of transient alteration of the cellular Na+ and K+ concentration.
      Vasopressin and PMA inhibited Na(+)-dependent bile acid uptake, at least in part,
      through protein kinase C activation.

PMID- 8997254
TI  - Evidence for Cl(-)-independent HCO3- transport in basolateral membranes of
      Necturus oxyntopeptic cells.
AB  - Luminal H+ secretion by gastric mucosa is accompanied by basolateral HCO3-
      release. A basolateral Cl-/HCO3- exchanger is known to mediate HCO3- extrusion
      from oxyntopeptic cells during resting and secretagogue-induced apical HCl
      secretion. From recent work, we hypothesized that there might be a Cl(-)
      independent pathway for basolateral HCO3- exit in Necturus oxyntopeptic cells. In
      this study, we used a fluorescent pH indicator [2',7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein] to evaluate Cl(-)-independent HCO3- transport across the
      basolateral membranes of intact oxyntopeptic cells. Removal of serosal Cl-
      increased intracellular pH (pHi) (7.05 to 7.25), consistent with Cl(-)-dependent
      HCO3- extrusion. Removal of serosal Na+ in the absence of Cl- resulted in
      significant acidification of pHi (7.10 to 6.89), but studies involving amiloride,
      4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and 0 HCO3(-)-N-2
      hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered solutions suggest that
      Na(+)-dependent changes in pHi are due to Na+/H+ exchange. Our studies
      demonstrate a marked concentration-dependent alkalinization when tissues are
      exposed to increases in serosal K+. A substantial part of this alkalinization in
      response to increases in serosal K+ (pHi 7.00 to 7.46) appears to be a HCO3- exit
      pathway that is independent of both Na+ and Cl-, unaffected by bumetanide or
      amiloride, but sensitive to DIDS. We propose the presence of a Cl(-)- and Na(+)
      independent K(+)-dependent HCO3- cotransporter in Necturus oxyntopeptic cell
      basolateral membranes.

PMID- 8997255
TI  - Canine H(+)-K(+)-ATPase alpha-subunit gene promoter: studies with canine parietal
      cells in primary culture.
AB  - H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) is the principal enzyme
      responsible for the process of gastric acid secretion. This enzyme is expressed
      in a cell-type-specific manner in gastric parietal cells. To explore the
      mechanisms regulating its expression, we transfected differentiated canine
      parietal cells in primary culture with H(+)-K(+)-ATPase-luciferase reporter genes
      and assessed transcriptional activities. Deletional analysis of the 5'-flanking
      region of this gene demonstrated a remarkable increment in transcriptional
      activity associated with a segment between bases -54 to -45 (5' GCTCCGCCTC 3')
      relative to the transcriptional initiation site. Gel shift assays with
      competition and supershift analysis demonstrated that this segment is
      specifically bound by the transcription factor Sp1. A point mutation, eliminating
      Sp1 binding, diminished basal transcriptional activity by 80%, indicating that
      this Sp1 binding site is important for constitutive transcriptional activity.
      Although these studies indicate that Sp1 is required to maintain a high
      concentration of the H(+)-K(+)-ATPase gene in the parietal cell, its cell-type
      specific expression must rely on other elements because Sp1 is a ubiquitously
      expressed transcription factor.

PMID- 8997256
TI  - Pertussis toxin alters the concentration and turnover of manganese superoxide
      dismutase in rat lung.
AB  - Treatment of rats with pertussis toxin (PTX) decreases the activity of manganese
      superoxide dismutase (Mn-SOD) in the lung and results in oxygen toxicity in air
      (L. B. Clerch, G. Neithardt, U. Spencer, J. A. Melendez, G. D. Massaro, and D.
      Massaro. J. Clin. Invest. 93: 2482-2489, 1994). To examine aspects of the
      mechanism of the PTX-induced fall in Mn-SOD activity, we injected rats with PTX
      (50 micrograms/kg), killed the rats 72 h later, and measured the activity,
      concentration, specific activity, and turnover of Mn-SOD in the lung. Treatment
      with PTX caused an approximately 50% fall in Mn-SOD activity and Mn-SOD
      concentration but no change in Mn-SOD specific activity. PTX also caused an
      increase in Mn-SOD mRNA concentration, a fall in Mn-SOD synthesis, and an
      increase in the half-life of Mn-SOD and general proteins. We conclude the PTX
      induced low concentration of Mn-SOD is due to a decrease of translational
      efficiency. We suggest that, under normoxic conditions, signal transduction via
      heterotrimeric guanine nucleotide binding proteins regulates the expression of Mn
      SOD at the level of translation and Mn-SOD degradation.

PMID- 8997257
TI  - Basic fibroblast growth factor induces expression of the PDGF receptor-alpha on
      human bronchial smooth muscle cells.
AB  - Bronchial smooth muscle cell (SMC) hyperplasia is a key feature in the pathology
      of asthma. Platelet-derived growth factor (PDGF) isoforms are SMC mitogens. We
      investigated the effect of basic fibroblast growth factor (bFGF), transforming
      growth factor-beta 1 (TGF-beta 1), interleukin-1 beta (IL-1 beta), and tumor
      necrosis factor-alpha (TNF-alpha) on the PDGF receptor system on human bronchial
      SMC from three different donors. bFGF induced gene expression of the PDGF alpha
      receptor (PDGF-R alpha) approximately threefold without altering the PDGF beta
      receptor (PDGF-R beta). IL-1 beta and TNF-alpha did not affect the PDGF receptor
      system. TGF-beta 1 downregulated PDGF-R alpha mRNA approximately 60% without
      changing PDGF-R beta mRNA levels. Receptor assays showed that bFGF increased the
      [125I]PDGF-AA binding site approximately twofold, whereas TGF-beta 1 reduced
      [125I]PDGF-AA binding approximately 60%. TGF-beta 1, but not latent TGF-beta 1,
      counteracted the bFGF-induced increase in [125I]PDGF-AA binding. PDGF-AA
      stimulated tyrosine phosphorylation on the PDGF-R alpha was enhanced after
      treatment with bFGF, bFGF pretreatment enhanced the mitogenic response of SMC to
      PDGF-AA and PDGF-AB. These findings suggest that upregulation of the PDGF-R alpha
      by bFGF could contribute to SMC hyperplasia during chronic airway inflammation in
      asthma.

PMID- 8997258
TI  - Protective effect of substance P on permeability of airway epithelial cells in
      culture.
AB  - Although substance P (SP) has been shown to mediate microvascular leakage in
      response to various stimuli, some data suggest that, in contrast, SP may play a
      protective role in the maintenance of airway epithelial integrity. To investigate
      the effect of SP on epithelial barrier function, we measured paracellular
      mannitol flux and the transepithelial potential difference (PD) of human
      bronchial epithelial (HBE) and canine bronchial epithelial (CBE) cells.
      Incubation of confluent cell cultures with SP had no effect on baseline flux.
      However, pretreatment inhibited the flux-enhancing effects of 0.5 ppm ozone by
      50% in HBE cells and 40% in CBE cells and inhibited the ozone-induced decrease in
      PD in CBE cells by 54%. SP-afforded protection was reduced by the neurokinin (NK)
      1 receptor antagonist CP-96,345.NK1 and NK3 receptor agonists also inhibited
      ozone-induced permeability, whereas an NK2 receptor agonist was without
      significant effect. These data indicate that SP exerts a protective effect on
      bronchial epithelial barrier function under conditions of challenge, which
      appears to be mediated in large part through NK1 receptors.

PMID- 8997259
TI  - Increase of lung sodium-potassium-ATPase activity during recovery from high
      permeability pulmonary edema.
AB  - Previous studies have suggested that recovery from pulmonary edema may be
      dependent on active sodium ion transport. Most of the data supporting this
      concept came from work done in isolated type II cells, isolated lung
      preparations, or in models of alveolar flooding. There is a limited amount of
      information regarding the role of active sodium ion transport in vivo.
      Furthermore, most of this information was obtained in one model of pulmonary
      edema, the hyperoxic lung injury model. The purpose of these experiments was then
      to measure the activity of the sodium-potassium-adenosinetriphosphatase (Na(+)
      K(+)-ATPase), the active component of the sodium transport process and an
      indirect marker of active sodium transport, during recovery from thiourea-induced
      pulmonary edema in rats. Na(+)-K(+)-ATPase activity was significantly increased
      during recovery from lung edema. This increase could not be accounted for by the
      Na(+)-K(+)-ATPase activity present in inflammatory cells recruited in the lung by
      the injury process or by a direct impact of thiourea on the enzyme. Alveolar
      flooding, induced by instillation of a protein-containing solution into the
      airways of ventilated rats also increased the activity of Na(+)-K(+)-ATPase,
      suggesting that activation of the enzyme is probably secondary to either the
      presence of edema or the physiological consequences associated with edema. The
      quantity of lung Na(+)-K(+)-ATPase protein was also elevated during edema
      resolution, indicating that augmented synthesis of this enzyme underlies the
      increased enzyme activity observed. The quantity of Na(+)-K(+)-ATPase protein in
      alveolar type II cells was also significantly enhanced during recovery from
      edema, suggesting that these cells contribute to active sodium transport in vivo.
      The results of this study suggest that active sodium transport could participate
      in the resolution of pulmonary edema.

PMID- 8997260
TI  - Response of airway smooth muscle cells to TGF-beta 1: effects on growth and
      synthesis of glycosaminoglycans.
AB  - Transforming growth factor-beta (TGF-beta) is formed in the airways and may have
      a role in airway remodeling in asthma. We have studied the effects of TGF-beta on
      bovine airway smooth muscle cells (BASMC) in vitro. Thymidine incorporation by
      BASMC was inhibited after a 24-h incubation with TGF-beta 1. In contrast,
      thymidine incorporation by BASMC was stimulated (35.1 +/- 11.2%) after a 48-h
      incubation with 1 ng/ml TGF-beta 1. Cell number was also increased (25.9 +/-
      7.6%) after a 72-h incubation with 3 ng/ml TGF-beta 1. TGF-beta 1 also increased
      cell size at 72 h, with a 24.3 +/- 6.2% increase in cell, diameter. Increases in
      BASMC size were accompanied by increased [3H]proline incorporation into cell
      protein. In cells from any individual animal, there was a strong inverse
      correlation (r = -0.97) between changes in cell number and cell size. In cells
      from some animals, the main effect of TGF-beta 1 was to promote an increase in
      cell number, whereas in others the predominant effect was cell hypertrophy. In
      contrast epidermal growth factor (EGF) led to an increase in thymidine
      incorporation and cell number in all preparations but did not increase cell size.
      TGF-beta 1 also promoted secretion of glycosaminoglycans into culture medium by
      BASMC with a preferential increase in hyaluronan secretion (4.5-fold) after 24 h.
      Latent TGF-beta (0.89 +/- 0.06 ng/ml) was also detected in conditioned medium
      from cultured BASMC, and TGF-beta 1 expression was demonstrated with RNA extracts
      from BASMC. Varying degrees of both smooth muscle cell hypertrophy and
      hyperplasia occur in asthma. These results obtained with airway smooth muscle
      cells indicate that TGF-beta could play a role in the structural changes seen in
      asthma.

PMID- 8997261
TI  - P-selectin-mediated attachment of small cell lung carcinoma to endothelial cells.
AB  - Small cell lung carcinoma (SCLC) frequently metastasizes early in the course of
      the disease. P-selectin (P-sel), a cell adhesion molecule expressed on activated
      platelets and endothelial cells (EC), has previously been demonstrated to mediate
      binding of platelets to SCLC. We hypothesized that P-sel facilitates attachment
      of SCLC to EC, acting as an important factor in SCLC metastasis. To test this
      hypothesis, attachment of H82 cells (SCLC cell line) to EC was quantified.
      Attachment of H82 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated
      EC was increased compared with control EC. Increased attachment of H82 cells to
      EC was apparent after 10 min of TPA activation, reached a peak after 30 min, and
      returned to baseline after 120 min of exposure. The TPA-induced increase in H82
      cell attachment to EC was inhibited by addition of anti-P-sel antibodies but not
      by addition of anti-E-selectin antibodies. The TPA-induced increase in H82 cell
      attachment was likely mediated by activation of EC protein kinase C (PKC).
      Pretreatment of the EC with PKC inhibitors effectively blocked the TPA-mediated
      increase in H82 cell attachment. In addition, prolonged exposure of EC to TPA
      resulted in decreased expression of the PKC-alpha and PKC-epsilon isoforms. These
      data indicate for the first time that attachment of SCLC to activated EC appears
      to be mediated by increased expression of P-sel on the EC surface, which may
      result from activation of specific isoforms of PKC.

PMID- 8997263
TI  - IL-1 beta stimulates superoxide and delayed peroxynitrite production by pulmonary
      vascular smooth muscle cells.
AB  - Our previous studies have shown that rat pulmonary microvascular smooth muscle
      cells (RPMSMC) upregulate inducible nitric oxide synthase (iNOS) and produce
      nitric oxide (NO) when treated with interleukin-1 beta (IL-1 beta). We now report
      that an additional effect of IL-1 beta stimulation in RPMSMC is an increase in
      production of superoxide (O2-) that results in the formation of peroxynitrite
      (ONOO-). IL-1 beta produced a rapid (within 1 h) concentration-dependent increase
      in O2-, as detected by ferricytochrome c reduction and lucigenin-enhanced
      chemiluminescence. O2- production was sensitive to quinacrine and
      diphenyliodinium, suggesting that NADH and NADPH oxidoreductases were
      responsible. After induction of iNOS and production of iNOS-derived NO, ONOO- was
      detected by luminol-enhanced chemiluminescence and was found to cause lipid
      peroxidation and to form nitrotyrosine in the cytoskeleton, detected by
      immunostaining. Cell viability, however, appeared to be unaffected. IL-1 beta
      mediated induction of RPMSMC-derived ONOO- may have significant effects on
      pulmonary vascular function in sepsis and inflammatory states.

PMID- 8997262
TI  - Effects of U-37883A, a vascular selective KATP+ channel antagonist, in the
      pulmonary and hindlimb circulation.
AB  - The effects of the vascular selective nonsulfonylurea guanidine ATP-sensitive K+
      (KATP+) channel-blocking agent U-37883A on vasodilator and vasoconstrictor
      responses were investigated in the pulmonary and hindlimb vascular beds of the
      cat. Under elevated tone conditions, both U-37883A and the sulfonylurea KATP+
      antagonist, glibenclamide, attenuated pulmonary vasodilator responses to the
      KATP+ channel openers without altering responses to vasodilator agents that are
      reported to act by KATP(+)-independent mechanisms. However, under low resting
      tone conditions, U-37883A enhanced pulmonary vasoconstrictor responses to the
      thromboxane mimic U-46619 and to prostaglandin (PG) F2 alpha and PGD2, whereas
      glibenclamide antagonized responses to U-46619 and the vasoconstrictor PG. In the
      hindlimb vascular bed, U-37883A and glibenclamide had no effects on responses to
      U-46619 in doses that inhibited vasodilator responses to the KATP+ channel opener
      levcromakalim. U-37883A and glibenclamide had no significant effect on baseline
      tone in the pulmonary or hindlimb vascular beds, and neither U-37883A nor
      glibenclamide altered pulmonary vasodilator responses to PGE1. The results of the
      present investigation show that U-37883A and glibenclamide, agents that are used
      in the study of vascular smooth muscle KATP+ channel mechanisms and attenuate
      vasodilator responses to the KATP+ channel openers, have pronounced effects on
      thromboxane/PG receptor-mediated vasoconstrictor responses in the pulmonary
      vascular bed of the cat.

PMID- 8997265
TI  - Early divergent lung antioxidant enzyme expression in response to
      lipopolysaccharide.
AB  - Lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria,
      interacts with eukaryotic cells, causing changes in gene expression and a rapid
      increase in the formation of superoxide and H2O2. We now report that, within 6 h
      of treating rats with LPS, there was a divergent response in the lung of
      manganese superoxide dismutase (Mn-SOD) and catalase expression without a change
      in expression of copper-zinc superoxide dismutase or glutathione peroxidase. The
      activity and mRNA concentration of Mn-SOD increased during the time catalase mRNA
      concentration and activity decreased. These divergent changes and activation of
      nuclear factor-kappa B (NF-kappa B) were preceded by a fall, 1 h after LPS
      treatment, in the RNA binding activity of two redox-sensitive proteins: Mn-SOD
      RNA binding protein and catalase RNA binding protein. The rapid onset of these
      changes, the bacteriostatic properties of H2O2, and the signaling function of NF
      kappa B suggest that the divergent expression of Mn-SOD and catalase is a
      coordinated component of the acute phase reaction to bacterial invasion.

PMID- 8997264
TI  - Effect of okadaic acid on elastin gene expression in interstitial lung
      fibroblasts.
AB  - Okadaic acid (OA), a specific serine/threonine protein phosphatase inhibitor,
      downregulated tropoelastin formation and elastin mRNA levels in a dose-related
      and cycloheximide-sensitive fashion in cultured lung fibroblasts. Treatment with
      a tyrosine phosphatase inhibitor at high concentrations did not alter elastin
      mRNA levels, however. Nuclear run-on analysis indicated that OA primarily
      suppressed elastin gene expression through a transcriptional mechanism. In
      contrast to its effects on elastin expression, OA downregulated alpha 1(I) mRNA
      to significantly lesser degrees. The mechanism by which OA decreased elastin mRNA
      levels did not appear to involve protein kinase C or share the signaling pathway
      of IL-1 beta. Prolonged treatment with phorbol ester promoted the inhibitory
      effects of OA on elastin, as did shorter treatment with IL-1 beta. Moreover,
      transient transfection studies indicated that OA and IL-1 beta do not act through
      the same cis-acting element in the elastin promoter. Finally, unlike the
      transient effects of IL-1 beta, OA induced persistent inhibition of elastin
      expression by a transcriptional mechanism. Taken together, these data indicate
      that serine/threonine protein phosphorylation can regulate the amount and
      composition of extracellular matrix secreted by fibroblasts into the interstitium
      of the lung.

PMID- 8997266
TI  - Effects of hypoxia on expression of superoxide dismutases in cultured ATII cells
      and lung fibroblasts.
AB  - This study investigated whether hypoxia affected the expression of mitochondrial
      manganese-containing superoxide dismutase (Mn-SOD) and the cytosolic copper and
      zinc-containing superoxide dismutase (Cu,Zn-SOD) in alveolar type II epithelial
      (ATII) cells and lung fibroblasts. Cells were exposed in vitro to air (controls)
      or to 2.5% oxygen (hypoxia) for 24 h. Mn-SOD and Cu,Zn-SOD mRNA expression was
      measured by quantitative reverse transcriptase-polymerase chain reaction. Both Mn
      SOD and Cu,Zn-SOD mRNA expression in ATII cells decreased significantly after 1
      day in hypoxic conditions. The decrease in Mn-SOD mRNA (-69%) was greater than
      that in Cu,Zn-SOD mRNA (-48%). ATII cell surfactant protein A transcript
      expression remained constant. Mn-SOD (-52%) and Cu,Zn-SOD (-54%) mRNA expression
      decreased similarly in lung fibroblasts cultured during hypoxia. The half-life of
      the Mn-SOD mRNA measured in lung fibroblasts exposed to air or hypoxia for 24 h
      decreased significantly from 5.8 +/- 0.1 to 3.8 +/- 0.7 h (-34%). The half-life
      for the Cu,Zn-SOD decreased significantly from 4.0 +/- 0.3 to 2.4 +/- 0.1 h (
      40%). Neither Mn-SOD nor Cu,Zn-SOD protein expression in ATII cells changed
      significantly during hypoxia. Hypoxia decreases expression of Mn-SOD and Cu,Zn
      SOD mRNA in ATII cells and lung fibroblasts in part by decreasing stability of
      the mRNA transcripts.

PMID- 8997267
TI  - Mechanism of RSV-induced IL-8 gene expression in A549 cells before viral
      replication.
AB  - Previous studies demonstrated that respiratory syncytial virus (RSV) infection of
      A549 cells induced interleukin (IL)-8 gene expression and protein release from
      the cells as early as 2 h after treatment [M. A. Fiedler, K. Wernke-Dollries, and
      J. M. Stark. Am. J. Physiol. 269 (Lung Cell. Mol. Physiol. 13): L865-L872, 1995;
      J. G. Mastronarde, M. M. Monick, and G. W. Hunninghake. Am. J. Respir. Cell Mol.
      Biol. 13: 237-244, 1995]. Furthermore, the effects of RSV at the 2-h time point
      were not dependent on viral replication. The studies reported here were designed
      to test the hypothesis that active and inactive RSV induce IL-8 gene expression
      in A549 cells at the 2-h time point by a mechanism dependent on the activation of
      the nuclear transcription factor NF-kappa B Northern blot analysis indicated that
      IL-8 gene expression occurred independent of protein synthesis 2 h after A549
      cells were treated with RSV. Analysis of nuclear extracts from RSV-treated A549
      cells by electrophoretic mobility shift assays demonstrated that NF-kappa B was
      activated as early as 15 min after RSV was added to the cells and remained
      activated for at least 90 min. In contrast, baseline levels of NF-IL-6 and
      activator protein-1 (AP-1) did not change over this period of time.
      Deoxyribonuclease footprint analysis of a portion of the 5'-flanking region of
      the IL-8 gene demonstrated two potential regions for transcription factor
      binding, which corresponded to the potential AP-1 binding site, and potential NF
      IL-6 and NF-kappa B binding sites. Mutational analysis of the 200-bp 5'
      untranslated region of the IL-8 gene demonstrated that activation of NF-kappa B
      and NF-IL-6 were required for RSV-induced transcriptional activation of the IL-8
      gene.

PMID- 8997268
TI  - Expression of fibronectin mRNA splice variants by rabbit lung in vivo and by
      alveolar type II cells in vitro.
AB  - Fibronectin (FN) is a multidomain glycoprotein with putative functions in tissue
      development and repair. In repair of alveolar injury, FN may promote the
      transition of type II epithelial cells to type I epithelial cells. Alternative
      splicing of FN mRNA, including the EIIIA and EIIIB exons, results in protein
      isoforms that have cell, tissue, and developmental specificity. The present work
      found that FN mRNA with the EIIIA exon was in fetal, adult, and oxidant-injured
      lung. The EIIIB splice variant, however, was restricted to fetal lung and adult
      lung recovering from oxidant injury. Because alveolar type II cells in vitro
      express FN, we examined the splice variants in two conditions that induce FN
      [transforming growth factor-beta 1 (TGF-beta 1) treatment and time in culture].
      TGF-beta 1 increased both EIIIA and EIIIB mRNA abundance by 10-fold. Increased
      EIIIA isoform immunostaining was also noted. Type II cells that spontaneously
      express FN at 72 h in vitro had increased EIIIA and EIIIB mRNA and increased
      immunostaining for EIIIA. Nuclear runoff showed induction of FN gene
      transcription at 72 h in vitro. Together, these data show differential FN splice
      variant expression in lung, with EIIIB mRNA restricted to fetal and recovering
      oxidant-injured lung. Furthermore, the transition of type II cells to a type I
      like cell is accompanied by increased FN gene transcription and induction of both
      EIIIA and EIIIB mRNA.

PMID- 8997269
TI  - Hyporesponsiveness to inhaled nitric oxide in isolated, perfused lungs from
      endotoxin-challenged rats.
AB  - Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves
      oxygenation in patients with the adult respiratory distress syndrome (ARDS).
      Approximately 30% of ARDS patients fail to respond to iNO. Because sepsis
      syndrome often accompanies a decreased response to iNO, we investigated NO
      responsiveness in isolated, perfused lungs from rats exposed to
      lipopolysaccharide (LPS). Eighteen hours after intraperitoneal injection of 0.5
      mg/kg LPS, rat lungs were isolated, perfused, and preconstricted with U-46619.
      Ventilation with 0.4, 4, and 40 parts per million by volume NO vasodilated LPS
      pretreated lungs 75, 47, and 42% less than control lungs (P < 0.01 value differs
      at each concentration). The diminished vasodilatory response to iNO was
      associated with decreased NO-stimulated guanosine 3',5'-cyclic monophosphate
      (cGMP) release into the perfusate. Soluble guanylate cyclase activity did not
      differ in lung extracts from LPS-pretreated and control rats. LPS increased
      pulmonary cGMP-phosphodiesterase (PDE) activity by 40%. The PDE-sensitive cGMP
      analogue 8-bromoguanosine 3',5'-cyclic monophosphate vasodilated lungs from LPS
      pretreated rats less than lungs from control rats. In contrast, the PDE
      insensitive 8-para-chlorophenylthioguanosine 3',5'-cyclic monophosphate
      vasodilated lungs equally from both groups. After LPS challenge, the rat
      pulmonary vasculature becomes hyporesponsive to iNO. Hyporesponsiveness to iNO
      appears partly attributable to increased pulmonary cGMP-PDE activity.

PMID- 8997270
TI  - Keratinocyte growth factor stimulates CFTR-independent fluid secretion in the
      fetal lung in vitro.
AB  - Keratinocyte growth factor (KGF) caused cystic dilation of mouse fetal lung
      explants in vitro, markedly increasing the luminal volume of lung buds and
      disrupting branching morphogenesis. Effects of KGF were dose dependent, were
      detected within 4 h of treatment, and were blocked by cycloheximide but not by
      actinomycin D, indicating that de novo protein synthesis mediated the response.
      Effects of KGF were inhibited by bumetanide, an inhibitor of the Na(+)-K(+)-Cl-
      cotransporter, and ouabain, an inhibitor of the Na(+)-K(+)-ATPase. KGF stimulated
      fluid secretion equally in lung buds from cystic fibrosis transmembrane
      conductance regulators (CFTR) -/- and wild-type embryos, indicating that the
      effects were mediated by CFTR-independent Cl- transport. Microelectrode studies
      demonstrated that, whereas KGF did not acutely alter the transepithelial
      potential difference (PD) across the respiratory epithelium, the PD decreased
      while luminal volume increased during chronic exposure. KGF inhibited expression
      of alpha-subunit of epithelial Na+ channel (alpha-ENaC) mRNA, suggesting that KGF
      may inhibit Na+ absorption, which may contribute to KGF-induced fluid
      accumulation. KGF-induced fluid accumulation is driven by CFTR-independent Cl-
      transport and associated with decreased expression of alpha-ENaC.

PMID- 8997271
TI  - Hydroxylation of salicylate in lungs of Fischer 344 rats: effects of aging and
      ozone exposure.
AB  - The formation of 2,3-dihydroxybenzoic acid (DHBA) from salicylate was measured in
      the lungs and plasma to assay for the .OH in juvenile (2 mo), adult (9 mo), and
      senescent (24 mo) Fischer 344 male rats exposed to clean air, 1 part/million
      (ppm) ozone, or 2 ppm ozone for 2 h. Similar rates of distribution of salicylic
      acid in plasma and to the lungs were observed among air control animals of all
      age groups. Levels of 2,3-DHBA were about twice as high in the lungs of air
      control senescent rats compared with juvenile and adult rats (P < 0.05). Exposure
      to ozone resulted in 1.5- to 2-fold elevation of 2,3-DHBA in lungs and plasma of
      all age groups (P < 0.05), whereas levels of 2,5-DHBA were not changed
      significantly. There was no effect of age on the magnitude of 2,3-DHBA increase
      in the lungs or plasma after ozone exposure. The postulated source of .OH is
      chemical reduction of H2O2, which could be generated from increased age-dependent
      endogenous oxidant production or the age-independent reaction of ozone or
      macrophage-derived oxidants with the surfactant lining.

PMID- 8997272
TI  - Colchicine inhibits arachidonate release and 5-lipoxygenase action in alveolar
      macrophages.
AB  - Although colchicine is known to inhibit leukotriene synthesis in neutrophils, its
      effect on other aspects of arachidonic acid (AA) metabolism as well as its
      mechanism of action are unknown. To address these questions, we investigated the
      effects of colchicine on resident rat alveolar macrophages (AM), cells that
      generate a variety of lipoxygenase and cyclooxygenase products after stimulation.
      Pretreatment of AM with 10 microM colchicine for 1 h dramatically inhibited the
      synthesis of all 5-lipoxygenase (5-LO) metabolites from endogenous AA in
      ionophore A-23187-stimulated cells. In addition, colchicine inhibited the total
      release of AA as well as prostanoids to a lesser extent. Similar effects were
      observed with the other microtubule-disruptive agents nocodazole and vinblastine,
      and 5-LO product formation stimulated by the particulate agonist zymosan was
      inhibited as well. A selective inhibitory effect of colchicine on the 5-LO
      pathway was demonstrated by monitoring the synthesis of 5-LO products from
      exogenously supplied AA. Cell-free enzyme assays showed that this effect was not
      through a direct inhibition of the 5-LO enzyme. Moreover, colchicine did not
      affect the translocation of 5-LO to the nuclear envelope. We next evaluated the
      effect of colchicine on the levels of the two 5-LO cofactors, ATP and Ca2+.
      Although colchicine did not affect ATP levels, it did abrogate the ionophore
      induced increase in intracellular Ca2+ concentration; the inhibitory effect of
      colchicine on 5-LO metabolism in AM was partially overcome by stimulation with
      higher doses of A-23187. We conclude that microtubular disruption inhibits
      agonist-induced increase in intracellular Ca2+ concentration, with multiple
      consequences for AA metabolism. These include a reduction in the liberation of AA
      from membrane phospholipids as well as the selective inhibition of processing of
      AA by 5-LO.

PMID- 8997273
TI  - Leukotriene D4 induces MMP-1, which functions as an IGFBP protease in human
      airway smooth muscle cells.
AB  - We have previously demonstrated that the asthma-associated proinflammatory
      eicosanoid leukotriene D4 (LTD4) is comitogenic with insulin-like growth factors
      (IGF) in airway smooth muscle (ASM) cells. This synergistic effect of LTD4 and
      IGF on ASM cell growth involves proteolysis of ASM-produced inhibitory IGF
      binding proteins (IGFBP). In this report, we analyzed the conditioned media (CM)
      from LTD4-treated human ASM cells (ASM-LTD4-CM) by Western ligand blotting and
      demonstrated a marked LTD4-induced reduction in the levels of the intact IGFBP
      (predominantly IGFBP-2) secreted by these cells. The IGFBP-2 in the ASM-LTD4-CM
      was identified as lower-molecular-weight fragments by Western immunoblotting.
      Incubation with 125I-labeled IGFBP demonstrated that an IGFBP protease was
      induced in the ASM cells in response to LTD4 treatment. Immunodepletion of ASM
      LTD4-CM with anti-matrix metalloproteinase (MMP)-1 antibodies demonstrated a dose
      dependent reduction of IGFBP proteolysis. Tissue inhibitor of MMP-1 and
      Batimastat (synthetic) inhibited proteolysis of IGFBP. Immunoblotting the ASM
      LTD4-CM with anti-MMP-1 demonstrated a dose-dependent increase in MMP-1 protein.
      Similar results were also obtained by immunocytochemistry. Collectively, these
      observations demonstrate that MMP-1 is an IGFBP protease induced by leukotrienes
      that plays a significant role in modulating IGF action in ASM cells. A similar
      mechanism may be applicable in vivo in the airways of patients with asthma.

PMID- 8997274
TI  - Quantitation of mucin RNA by PCR reveals induction of both MUC2 and MUC5AC mRNA
      levels by retinoids.
AB  - The polydispersity of most human secretory mucin messages has made them difficult
      to detect specifically and quantitatively, impeding the evaluation of the
      relative expression of the various mucin genes and their role in normal and
      pathological conditions. For this reason, we developed competitive reverse
      transcriptase-polymerase chain reaction (PCR) methods to measure the airway
      mucins MUC2 and MUC5AC. Oligonucleotide pairs were designed that specifically
      detect MUC2 and MUC5AC, as demonstrated by the size and sequence of the PCR
      product and the expected tissue distribution. The mucin oligonucleotide primers
      were used to synthesize internal competitive standards, called MIMIC. Using this
      assay, the relative expression of these messages was analyzed in retinoid-replete
      or -deprived cultures of normal human tracheobronchial epithelial (NHTBE) cells.
      Retinoid deficiency induces squamous metaplasia in vivo and in vitro. Consistent
      with these observations and in contrast to a previous report, retinoid-deprived
      cultures produced at least an order of magnitude less MUC2 and MUC5AC message
      than retinoid-replete cultures. In summary, this paper describes methodology that
      can be applied to the specific and quantitative measurement of mucin messages and
      demonstrates that, in NHTBE cells, the level of MUC2 and MUC5AC mRNA is increased
      by retinoids.

PMID- 8997275
TI  - Prostaglandin F2 alpha induces cardiac myocyte hypertrophy in vitro and cardiac
      growth in vivo.
AB  - Several prostaglandins [prostaglandin (PG) A2, -B2, -D2, -E2, -F2 alpha, and -I2
      and carbaprostacyclin] and the thromboxane analogue U-46619 were analyzed for the
      ability to induce hypertrophy of rat neonatal cardiac ventricular myocytes.
      Myocyte hypertrophy was induced specifically by PGF2 alpha. Myocytes exposed to
      this prostanoid in culture increased in size and protein content. The contractile
      fibrils within the cells became organized into parallel arrays, and the cells
      tended to cluster and beat spontaneously. PGF2 alpha also induced the expression
      of c-fos, atrial natriuretic factor (ANF), and alpha-skeletal actin in these
      cells. The effects of PGF2 alpha were compared with several known cardiac myocyte
      hypertrophy factors (phenylephrine, endothelin-1, leukemia inhibitory factor,
      cardiotrophin-1, and angiotensin II). PGF2 alpha was found to be intermediate in
      potency among the factors but induced a level of ANF production that was
      approximately 10-fold higher than any of the other effectors. Responsiveness to
      PGF2 alpha was not limited to neonatal cardiocytes. Ventricular myocytes isolated
      from adult rats also responded specifically to PGF2 alpha with a morphological
      change similar to that observed with phenylephrine and by producing ANF. In rats,
      chronic administration of fluprostenol, a potent agonist analogue of PGF2 alpha,
      resulted in a dose-dependent increase in heart weight- and ventricular weight-to
      body weight ratios. The amount of PGF2 alpha extractable from the hearts of rats
      with cardiac hypertrophy induced by myocardial infarction was also found to be
      greater than that in sham-operated control rats. These results indicate that PGF2
      alpha may play an important role in inducing cardiac hypertrophy.

PMID- 8997277
TI  - Baroreflex frequency-response characteristics to aortic depressor and carotid
      sinus nerve stimulation in rats.
AB  - Dynamic cardiovascular regulation depends on baroreflexes and the processing of
      sensory information. We evaluated the influence of choice of anesthetic on the
      frequency-response characteristics of the baroreflex of rats by electrical
      stimulation of two major baroreceptor-containing nerves, the carotid sinus (CSN)
      and aortic depressor nerves (ADN). The ADN contains baroreceptors alone, and the
      CSN has both chemoreceptors and baroreceptors. Most studies were performed under
      pentobarbital sodium (PB; 65 mg/kg) anesthesia. We compared this to a combination
      of alpha-chloralose (80 mg/kg) and urethan (800 mg/kg) (CU). Stimulus trains were
      fixed at 60-s periods (0.1-ms shocks, supramaximal intensities, 1-200 Hz) and
      delivered in steady and burst patterns. Unilateral steady-frequency ADN
      stimulation in PB-anesthetized rats evoked reflex decreases in mean arterial
      pressure and heart rate that increased with frequencies between 1 and
      approximately 10 Hz before reaching a maximum. From 10 to 200 Hz, PB ADN reflex
      responses were sustained at these maximal levels. Cutting the opposite ADN or
      both CSNs did not alter ADN baroreflex relationships. Heart rate and mean
      arterial pressure depressor responses evoked by CSN stimulation in PB
      anesthetized rats were smaller compared with ADN stimulation and were biphasic,
      with small pressor responses at 1 Hz. Maximal CSN depressor responses in PB
      anesthetized rats occurred at approximately 20 Hz and were sustained at 20-200
      Hz. Baroreflex responses for ADN stimulation in CU-anesthetized rats were similar
      to those in PB-anesthetized rats. In contrast, in CU-anesthetized rats, maximal
      CSN responses occurred at 20 Hz but declined at 50-200 Hz. Constant- and burst
      stimulation responses were equivalent. The results suggest that rat aortic
      baroreflex responses are sustained even at very high input frequencies (> 100
      Hz). The sustained high-frequency baroreflex responses seem to present a paradox
      in understanding central integration because other studies show substantial
      depression of sensory transmission at the first synapse in the nucleus tractus
      solitarius at frequencies as low as 10 Hz.

PMID- 8997276
TI  - Subcellular compartmentalization of Gs alpha in cardiac myocytes and its
      redistribution in heart failure.
AB  - Intracellular compartmentalization of G proteins may contribute to regulating
      signal transduction pathways in normal and failing myocardium. To test this
      hypothesis, we used postembedment immunogold electron microscopy to characterize
      the subcellular distribution of Gs alpha in normal canine and porcine left
      ventricular myocytes and in myocytes from a pacing-induced heart failure model in
      pigs in which beta-adrenergic signaling is impaired. Gs alpha was highly
      compartmentalized in normal canine myocytes and was localized specifically to the
      sarcolemma, intercalated disks, T-tubule and sarcoplasmic reticulum (SR) triads,
      and myoplasm. The highest Gs alpha concentration was observed in the intercalated
      disks. Only 20 +/- 5% of total cellular Gs alpha was localized to the sarcolemma.
      The triads and myoplasm compartments contained 45 +/- 13 and 27 +/- 8% of total
      cellular Gs alpha, respectively. The distribution of Gs alpha in normal porcine
      and canine myocytes was similar. However, in failing porcine myocytes Gs alpha
      was redistributed from the sarcolemma and T-tubule and SR triads to the myoplasm.
      The proportion of total cellular Gs alpha in the sarcolemma fell from 22 +/- 5 in
      normal to 11 +/- 4% in failing myocytes (P < 0.005), and the proportion in T
      tubule and SR triads fell from 55 +/- 5 to 40 +/- 5% (P < 0.01), with a
      quantitatively corresponding increase in the proportion in the myoplasm from 19
      +/- 3 to 43 +/- 4% (P < 0.0001). Thus redistribution of Gs alpha from the
      sarcolemma and the T-tubule and SR triads, where it may transduce beta-adrenergic
      signals, to internal sites where such actions may be precluded, might contribute
      to the pathophysiology of heart failure.

PMID- 8997278
TI  - Impairment of cGMP- and cAMP-mediated vasorelaxations in rats with chronic heart
      failure.
AB  - To elucidate pathophysiological alterations in vascular relaxation in rats with
      chronic heart failure (CHF), guanosine 3',5'-cyclic monophosphate (cGMP)- and
      adenosine 3',5'-cyclic monophosphate (cAMP)-mediated vasorelaxations in pulmonary
      artery (PA) and thoracic aorta (TA) of rats were examined 12 wk after coronary
      artery ligation. Acetylcholine (ACh)-induced relaxation was attenuated in
      endothelium-intact segments of both arteries, whereas sodium nitroprusside
      induced relaxation was attenuated only in endothelium-intact TA segments of rats
      with CHF. Vasorelaxations elicited by isoproterenol and NKH-477, a water-soluble
      forskolin analogue, were diminished mainly in PA segments of the CHF rat. NG
      nitro-L-arginine methyl ester (L-NAME)-induced decrease in cGMP level was less in
      endothelium-intact TA segments of the rat with CHF (0.20 +/- 0.06 vs. 0.99 +/-
      0.26 pmol/mg protein in control), suggesting that basal nitric oxide (NO)
      production is reduced in CHF. Treatment with L-NAME attenuated the isoproterenol
      induced relaxation only in endothelium-intact TA segments in control rats but not
      in CHF rats. The results suggest that both cGMP- and cAMP-mediated relaxations
      are impaired in CHF, and a reduction of NO synthesis, presumably in endothelial
      cells, plays a significant role in pathophysiological alterations in vessels of
      rats with CHF.

PMID- 8997279
TI  - Nitric oxide-dependent opposite effects of somatostatin on arterial and venous
      caliber in situ.
AB  - The vascular effects of somatostatin (ST) and its mechanism of action are not
      well understood. In the present study, we investigated the direct effects of ST
      on the vascular tone of rat saphenous artery and vein using videomicroangiometry
      in situ. ST was administered either in superfusion or in infusion. We found
      opposite effects in arteries and veins: ST (10(-12)-10(-7) M) dilated the artery
      (outer diameter increased from 533 +/- 28 to 600 +/- 29 microns, administered in
      superfusion) and contracted the vein (from 709 +/- 26 to 640 +/- 26 microns and
      from 775 +/- 30 to 708 +/- 60 microns in superfusion and infusion, respectively).
      These effects of ST were completely abolished after deendothelization (air bolus
      maintained for 6 min in vessel lumen) and after local infusion of NG-nitro-L
      arginine (L-NNA; 10(-4) M), a nitric oxide (NO) synthesis inhibitor. An NO
      dependent basal vasodilator tone in the rat saphenous vein responsible for 10.9
      +/- 0.3% of the total vessel diameter was found. After ST administration the
      venous diameter reduction was similar to that measured after deendothelization or
      L-NNA. We conclude that ST in situ induces NO release from endothelial cells of
      rat saphenous artery causing vasodilation, whereas, in contrast, it inhibits the
      basal NO-dependent vasodilator tone of the saphenous vein inducing
      vasoconstriction.

PMID- 8997280
TI  - Pulmonary vascular pressure effects by endothelin-1 in normoxia and chronic
      hypoxia: a longitudinal study.
AB  - The role of endothelin (ET)-1 in pulmonary arterial pressure (Ppa) homeostasis
      and hypoxia-induced pulmonary hypertension was examined. ET-1 was chronically
      infused (2 and 4 pmol.kg-1.min-1) into the pulmonary circulation of male Sprague
      Dawley rats for 3, 7, and 14 days while they were exposed to normoxia or
      hypobaric hypoxia (inspired O2 fraction 10%). The role of endogenous ET was
      examined by infusion of ET antiserum (ET-AS; 0.25 and 0.5 microliter.rat-1.h-1;
      cross-reacting with ET-1, -2, and -3) or the ETA-receptor blocker BQ-123 (10
      pmol.kg-1.min-1). ET-1 (4 pmol) increased Ppa at 3 and 7 days in normoxia and
      hypoxia and was ineffective at 14 days, probably from ETA-receptor
      downregulation. BQ-123 blunted the hypoxic Ppa rise at all times, confirming a
      role for ETA receptors. ET-AS (0.5 microliter) was mostly ineffective but
      exacerbated hypoxic Ppa at 14 days, in contrast to BQ-123, suggesting that a
      different ET receptor could be involved. ET-1 infusion (2 pmol) caused right
      ventricular hypertrophy (RVH) in normoxia and exacerbated RVH in hypoxia, whereas
      BQ-123 and ET-AS (0.25 microliter) reduced hypoxic RVH. In conclusion, endogenous
      ET-1 plays a role in hypoxia-induced pulmonary hypertension and RVH by augmenting
      the level of hypoxic response. ET-1 also affects hematocrit and may reduce blood
      levels of the vasodilator calcitonin gene-related peptide.

PMID- 8997281
TI  - In vivo inhibition of transcellular water channels (aquaporin-1) during acute
      peritoneal dialysis in rats.
AB  - During peritoneal dialysis (PD), a major portion of the osmotically induced water
      transport to the peritoneum can be predicted to occur through endothelial water
      selective channels. Aquaporin-1 (AQP-1) has recently been recognized as the
      molecular correlate to such channels. Aquaporins can be inhibited by mercurials.
      In the present study, HgCl2 was applied locally to the peritoneal cavity in rats
      after short-term tissue fixation, used to protect the tissues from HgCl2 damage.
      Dianeal (3.86%) was employed as dialysis fluid, 125I-albumin as an
      intraperitoneal volume marker, and 51Cr-EDTA (constantly infused intravenously)
      to assess peritoneal small-solute permeability characteristics.
      Immunocytochemistry and immunoelectron microscopy revealed abundant AQP-1
      labeling in capillary endothelium in peritoneal tissues, representing sites for
      HgCl2 inhibition of water transport. HgCl2 treatment reduced water flow and
      inhibited the sieving of Na+ without causing any untoward changes in
      microvascular permeability, compared with that of fixed control rats, in which
      the peritoneal cavity was exposed to tissue fixation alone. In fixed control
      rats, the mean intraperitoneal volume (IPV) increased from 20.5 +/- 0.15 to 25.0
      +/- 0.52 ml in 60 min, whereas in the HgCl2-treated rats, the increment was only
      from 20.7 +/- 0.23 to 23.5 +/- 0.4 ml. In fixed control rats, the dialysate Na+
      fell from 135.3 +/- 0.97 to 131.3 +/- 1.72 mM, whereas in the HgCl2-treated rats
      the dialysate Na+ concentration remained unchanged between 0 and 40 min, further
      supporting that water channels had been blocked. Computer simulations of
      peritoneal transport were compatible with a 66% inhibition of water flow through
      aquaporins. The observed HgCl2 inhibition of transcellular water channels
      strongly indicates a critical role of aquaporins in PD and provides evidence that
      water channels are crucial in transendothelial water transport when driven by
      crystalloid osmosis.

PMID- 8997282
TI  - Erythrocyte flux in capillary networks during maturation: implications for oxygen
      delivery.
AB  - Erythrocyte (RBC) flow variables were measured with videomicroscopy in hamster
      cremaster muscle capillary networks. Capillary networks consist of subgroups,
      termed modules, with architectural characteristics that are invariant with
      maturation [B. R. Berg and I. H. Sarelius. Am. J. Physiol, 268 (Heart Circ.
      Physiol. 37): H1215-H1222, 1995]. RBC flux in modules decreased from 82.0 +/- 4.3
      (SE) cells/s at 51 days of age to 59.5 +/- 7.5 and 27.5 +/- 2.8 cells/s at 65 and
      79 days of age, respectively. Mean cell velocity at 51 days (385 +/- 10
      microns/s) was higher than at 65 or 79 days (285 +/- 15 and 241 +/- 12 microns/s,
      respectively). Cell content (number of cells per unit length) decreased later,
      between 65 and 79 days (from 0.21 +/- 0.01 and 0.23 +/- 0.02 cells/micron at 51
      and 65 days, respectively, to 0.12 +/- 0.01 cells/micron at 79 days). These
      temporal differences in the decrease in cell velocity and cell content suggest
      different regulatory mechanisms. The capacity of capillary networks to deliver
      oxygen was modeled by using the calculated mean PO2 at the capillary wall to
      indicate the capacity to delivery oxygen. During maturation, the mean capillary
      wall PO2 remained unchanged (15.5 +/- 1.2 and 11.4 +/- 2.7 Torr in maximal
      dilation and 24.5 +/- 1.4 and 22.8 +/- 2.4 Torr at rest at 51 and 79 days,
      respectively). Thus, despite changes in RBC flow variables with maturation, the
      capacity for networks to deliver oxygen remains constant.

PMID- 8997284
TI  - Glycogen depletion contributes to ischemic preconditioning in the rat heart in
      vivo.
AB  - Ischemic preconditioning depletes the myocardium of glycogen, thus blunting
      lactic acidosis during subsequent episodes of ischemia. Preconditioning also
      protects against reperfusion arrhythmias and infarction. To test whether glycogen
      depletion is necessary for this ischemic tolerance, we preconditioned two groups
      of intact rats with a series of 3-min coronary artery occlusions. In one group,
      preconditioning lowered the glycogen concentration of the ischemic region by
      approximately 50% (24.9 +/- 2.5 to 12.5 +/- 1.8 mumol/g; P < 0.01). In the other,
      the heart was first loaded with glycogen via glucose-insulin infusion so that
      preconditioning merely reduced its glycogen concentration back to normal
      physiological levels. Compared with nonpreconditioned control rats,
      preconditioned rats with both normal and subnormal glycogen concentrations were
      protected from reperfusion arrhythmias after a 6-min coronary occlusion
      (incidence: control rats, 100%; normal glycogen rats, 11%; reduced glycogen rats,
      11%). In contrast, only rats with subnormal glycogen concentration after
      preconditioning exhibited reduced lactate formation and infarct size after a 45
      min coronary occlusion [infarct size (percentage of risk area): control rats, 53
      +/- 10%; normal glycogen rats, 50 +/- 16%, P = not significant; subnormal
      glycogen rats, 18 +/- 10%, P < 0.01]. Thus, in the intact rat, myocardial
      glycogen depletion appears to be necessary for the infarct-limiting, but not for
      the antiarrhythmic, effects of ischemic preconditioning.

PMID- 8997283
TI  - Regulation by acetylcholine of Ca2+ current in rabbit atrioventricular node
      cells.
AB  - Effects of acetylcholine (ACh) on L-type Ca2+ current (ICa) were examined in
      isolated atrioventricular (AV) node cells exhibiting spontaneous contractions and
      pacemaker current (If). ACh at a saturating concentration of 10 microM reduced
      basal ICa by 48 +/- 6%. The ACh effect was abolished by dialysis with 8
      bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), an adenosine 3',5'-cyclic
      monophosphate (cAMP)-dependent protein kinase inhibitor, or guanosine-5'-O-(2
      thiodiphosphate). Dialysis with guanosine 3',5'-cyclic monophosphate (cGMP) or NG
      monomethyl-L-arginine (L-NMMA) and application of the cGMP-dependent protein
      kinase inhibitor KT-5823 (1 microM) did not affect ACh inhibition of ICa. Nitric
      oxide donor 3-morpholinosydnonimine (100 microM) and type III phosphodiesterase
      (PDE) inhibitor trequinsin (10 nM) enhanced basal ICa by 10-20%, whereas type IV
      PDE inhibitor Ro-20-1724 (30 microM) together with trequinsin caused a large ICa
      stimulation comparable to that by 3-isobutyl-1-methylxanthine (IBMX). These
      findings indicate that ACh inhibits basal ICa primarily by suppressing cAMP
      synthesis and that these cells have a potent type III and IV PDE activity to
      determine the basal cAMP concentration. When ICa was stimulated by IBMX (100
      microM), the inhibitory effect of ACh was slightly reduced by L-NMMA, cGMP, and
      methylene blue but not by KT-5823 or Ro-20-1724. ACh hardly inhibited, or even
      enhanced, IBMX-stimulated Ica when forskolin (3 microM) was coapplied or the IBMX
      concentration was increased to 500 microM. These findings suggest that cAMP is
      degraded in the presence of 100 microM IBMX to some extent. Type II PDE, for
      which IBMX has a relatively high inhibitor constant, seems to contribute
      partially to the cAMP degradation.

PMID- 8997285
TI  - Low PO2 inhibits calcium channel activity in arterial smooth muscle cells.
AB  - We studied the effect of O2 tension (PO2) on the activity of voltage-gated Ca2+
      channels recorded in whole cell patch-clamped smooth muscle cells enzymatically
      dispersed from rabbit cerebral, celiac, femoral, and main pulmonary arteries, as
      well as from the porcine coronary artery. In all myocyte classes examined, a
      reduction of PO2 (hypoxia) produced a rapid and reversible inhibition of the
      macroscopic L-type Ca2+ current of similar general characteristics. The hypoxic
      inhibition of Ca2+ channel activity closely followed the time course of bath
      exchange, first becoming apparent at below approximately 80 mmHg PO2. The
      interaction of O2 with the Ca2+ channels was strongly voltage dependent. At -30
      mV the average extent of current inhibition was approximately 80%; however, no
      effect or even potentiation of current amplitude was observed at potentials more
      positive than +30 mV. Hypoxia selectively slowed activation kinetics
      (approximately 1.5 times at -20 mV); however, channel deactivation and
      inactivation were unaltered by low PO2. In addition, hypoxia produced a
      reversible shift (8.1 +/- 1.0 mV, n = 12) of the Ca2+ conductance-voltage curve
      toward positive membrane potentials. We propose that the O2 sensitivity of Ca2+
      channels may contribute to the well-known hypoxic dilatation of systemic and the
      main pulmonary arteries.

PMID- 8997286
TI  - Dynamics of myocardial adaptation to low-flow ischemia and hypoxemia.
AB  - We investigated whether one or more factors control performance in O2-limited
      hearts. For this purpose, we measured the dynamics of myocardial adaptation to
      reduced O2 supply with a specially designed setup, analyzing early changes after
      reduction in either flow of the perfusion medium or its PO2. For 10 min, 38
      isolated rat hearts underwent low-flow ischemia or hypoxemia, matched for O2
      supply. Early during ischemia, developed pressure declined at a rate of 311 +/-
      25 mmHg/s; lactate release increased and then leveled off to 3.4 +/- 0.7
      mumol/min within 2 min. During hypoxemia, pressure dropped initially, as observed
      during ischemia. However, it then increased before slowly decreasing. Lactate
      release during hypoxemia peaked at 13.0 +/- 2.3 mumol/min after 2 min, leveling
      off to 3.5 +/- 1.3 mumol/min. Glycogen decreased by 52 and 81% in ischemic and
      hypoxemic hearts, respectively (P < 0.05). Reexposure to ischemia or hypoxemia
      induced comparable changes in both groups. We conclude that, at the beginning of
      ischemia, a single factor does limit myocardial performance. This variable, which
      remains undisturbed for 10 min, is presumably O2 availability. In contrast,
      approximately 20 s after induction of hypoxemia, glycolytic ATP production can
      partially override low O2 availability by providing most of the energy needed.
      During repeated restriction of O2 supply, O2 availability alone limits
      performance during both ischemia and hypoxemia.

PMID- 8997287
TI  - Renal hemodynamics in rats with myocardial infarction: selective antagonism of
      angiotensin receptor subtypes.
AB  - Rats with congestive heart failure demonstrate striking intrarenal
      vasoconstriction that contributes to reduced renal excretory function. The
      importance of specific angiotensin II receptor subtypes (AT1, AT2) for mediating
      changes in renal hemodynamics was studied in anesthetized rats 1 mo after
      myocardial infarction (MI) created by coronary artery ligation. AT1 antagonism
      with losartan alone decreased mean arterial pressure (MAP), total peripheral
      resistance (TPR), and renal resistance (RR) in control and MI rats to a similar
      extent without affecting renal blood flow (RBF) or RBF as a percentage of cardiac
      output (%RBF/CO). In contrast, AT2 antagonism with PD-123319 alone significantly
      reduced MAP and RR in MI rats without affecting these parameters in control rats.
      TPR and %RBF/CO were not changed significantly in either group. In contrast,
      combined AT1- and AT2-receptor inhibition lowered TPR and RR and increased RBF
      and %RBF/CO, thus the effects of renin or ACE inhibition were mimicked in MI
      rats. We conclude that angiotensin II acts at both AT1 and AT2 receptor sites in
      rats with reduced cardiac mass to modulate renal hemodynamics.

PMID- 8997288
TI  - Developmental changes in alpha 1-adrenergic receptors, IP3 responses, and NE
      induced contraction in cerebral arteries.
AB  - Cerebral arteries show significant developmental and artery-specific changes in
      noradrenergic-mediated contraction. To test the hypothesis that these changes
      result from differences in the density of alpha 1-adrenergic receptors (alpha 1
      ARs) and/or norepinephrine (NE)-induced inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3,IP3] synthesis, we quantified these variables and the NE-induced
      contraction in the common carotid artery (Com) and main branch cerebral arteries
      (MBC) from term fetal (approximately 140 gestational day) and newborn (2- to 5
      day) sheep and compared them with adult values. In fetal and newborn Com, maximal
      contractions to NE (percent K+ maximum response) were 132 +/- 14 and 118 +/- 9%,
      respectively (adult = 92 +/- 7%). For fetal and newborn middle cerebral artery,
      these values were 34 +/- 10 and 43 +/- 7%, respectively (adult = 24 +/- 7%).
      alpha 1-AR density values in Com of fetal and newborn sheep were 113 +/- 18 and
      106 +/- 4 fmol/mg protein, respectively (adult = 54 +/- 3 fmol/mg protein). For
      the MBC, density values were 47 +/- 2 and 24 +/- 3 fmol/mg protein, respectively
      (adult = 23 +/- 3 fmol/protein). In term fetal and newborn MBC, NE produced dose
      dependent increases in Ins(1,4,5)P3, the maximal increases above basal values
      being 245 +/- 40 and 189 +/- 16%, respectively (adult = 254 +/- 35%). Neither
      fetus nor newborn Com showed significant Ins(1,4,5)P3 responses to NE. We
      concluded that in fetal and newborn Com and MBC, alpha 1-AR density and NE
      induced Ins(1,4,5)P3 response varied as a function of developmental age and
      specific vessel. However, these variations did not correlate with NE-induced
      maximum contraction. Thus we reject the hypothesis that age-dependent and vessel
      specific differences of cerebral artery adrenergic-mediated contraction are a
      function of alpha 1-AR density or Ins(1,4,5)P3 response. Rather, the differences
      would appear to result from other factors such as non-Ins(1,4,5)P3-mediated
      calcium activation and/or sensitivity to Ins(1,4,5)P3. The studies also suggest
      considerable potential for maturational modulation of pharmacomechanical coupling
      and homeostatic regulation of cerebrovascular tone.

PMID- 8997290
TI  - Changes in angiotensin II receptor density and calcium handling during
      proliferation in SHR aortic myocytes.
AB  - The aim of the present work was to characterize angiotensin II (ANG II) receptors
      and their effect on intracellular free Ca2+ concentration ([Ca2+]i) in
      proliferating aortic smooth muscle cells (VSMCs) from spontaneously hypertensive
      rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Independently from the
      proliferating state of cultures, apparent affinities of ligands (ANG II >
      losartan > > CGP-42112A) were consistent with the presence of AT1 receptors in
      primary cells from SHR and WKY. In proliferating cultures, increases in [Ca2+]i
      elicited by ANG II (100 nM) were dramatically attenuated or abolished in VSMCs
      from both strains compared with confluent and postconfluent cultures. Ca2+
      releases induced by ionomycin and by ANG II in the absence of extracellular Ca2+
      were also impaired in proliferating cultures. In addition, no significant strain
      difference was found in proliferating cultures with respect to ANG II receptor
      density, basal [Ca2+]i, and ANG II-induced increases in [Ca2+]i. However, ANG II
      receptor density significantly increased in SHR, but not in WKY VSMCs at
      postconfluence. Furthermore, basal [Ca2+]i was elevated in confluent and
      postconfluent cultures from SHR but not WKY. In confluent cultures, ANG II- and
      ionomycin-induced Ca2+ releases were enhanced in SHR VSMCs compared with WKY
      VSMCs. These results show that ANG II-induced Ca2+ release and ionomycin
      sensitive Ca2+ stores are enhanced in SHR VSMCs but dramatically decreased in
      proliferating VSMC cultures from both strains. Mechanisms underlying these
      alterations remain to be defined. However, the results suggest that alterations
      in ANG II AT1 receptor density and in intracellular Ca2+ handling in confluent
      and postconfluent cultures are not associated with the proliferative phenotype of
      SHR VSMCs. In addition, no evidence for any change in ANG II receptor subtype
      associated with proliferation of VSMCs was found in either strain.

PMID- 8997289
TI  - Impaired pyruvate oxidation but normal glucose uptake in diabetic pig heart
      during dobutamine-induced work.
AB  - We tested the hypothesis that diabetes impairs myocardial glucose uptake and
      pyruvate oxidation under normal conditions and during a dobutamine-induced
      increase in work. We also tested the hypothesis that an increase in work would
      result in a decrease in the levels of malonyl CoA, a potent inhibitor of
      carnitine palmitoyltransferase I (CPT I). Streptozotocin-diabetic micropigs were
      compared with a nondiabetic control group (n = 8 per group). Triglyceride
      emulsion, glucose, and somatostatin were infused into the nondiabetic group to
      create an acute diabetic-like state. In accord with our hypothesis, malonyl CoA
      decreased significantly with dobutamine in both groups, providing a possible
      mechanism for increased fatty acid oxidation through relieved inhibition on CPT
      I. In the absence of dobutamine, glucose uptake and tracer-measured lactate
      uptake were decreased by 57 and 80%, respectively, in the diabetic group.
      Dobutamine infusion resulted in similar increases in cardiac contractility,
      oxygen consumption, and glucose uptake in both groups despite reductions of 50
      65% in GLUT-4 and GLUT-1 protein in the diabetic group. Diabetic animals
      possessed a defect in myocardial pyruvate oxidation, as reflected in increased
      lactate production, and depressed lactate uptake and pyruvate dehydrogenase
      activity under control and dobutamine conditions. In conclusion, the major
      derangement in carbohydrate metabolism in diabetic myocardium was not in
      glycolysis but, rather, in pyruvate oxidation.

PMID- 8997291
TI  - ATP-sensitive potassium channels regulate stimulated ANF secretion in isolated
      rat heart.
AB  - Perfused hearts (n = 127) were exposed to acute hypoxia (10% O2 for 12 or 20 min)
      or left atrial stretch (increase in atrial pressure) in the presence or absence
      of 100 mumol/l ATP-sensitive potassium channel blocker (tolbutamide) or openers
      (pinacidil and diazoxide). Hypoxia alone elicited a prolonged atrial natriuretic
      factor (ANF) release, peaking at 74% over baseline (P < 0.01); with tolbutamide,
      ANF secretion peaked at 132% over baseline (P < 0.01). Pinacidil and diazoxide
      abolished the ANF response to hypoxia (P < 0.01). Atrial stretch alone (1 mmHg)
      transiently (2 min) increased ANF by 56% (P < 0.05); with tolbutamide, ANF
      increased transiently by 124% and showed a prolonged increase of 52% (P < 0.05).
      With tolbutamide, graded stretch (0.5-2.3 mmHg) induced a bell-shaped transient
      (2-min) increase of ANF release [-3% at 0.5 mmHg, 124% (P < 0.05) at 1.0 mmHg,
      80% (P < 0.05) at 1.48 mmHg, and 14% at 2.22 mmHg] and a saturating prolonged ANF
      response. Tolbutamide increased the ANF response nonsignificantly at lower doses
      (30 mumol/l) and had no effect at 1 mumol/l. Pinacidil abolished the stretch
      induced ANF release. These results suggest that ATP-sensitive potassium channels
      are extremely potent modulators of stimulated ANF secretion.

PMID- 8997292
TI  - Influence of acute-phase proteins on erythrocyte aggregation.
AB  - With the exception of fibrinogen, immunoglobulins, and albumin, little
      information is available on the effect of acute-phase proteins on erythrocyte
      aggregation. The objective of this study was to investigate the effects of
      haptoglobin (Hp), C-reactive protein (CRP), ceruloplasmin (Cp), alpha 1-acid
      glycoprotein (alpha 1-AGP), and alpha 1-antitrypsin (alpha 1-AT) on the
      aggregation kinetics and shear resistance of erythrocyte aggregates. The plasma
      concentration of these proteins was measured in 20 healthy individuals and kept
      unchanged while the concentration of the protein tested was increased. Adding Hp
      to concentrations between 2.78 and 4.99 g/l resulted in a significant progressive
      increase in aggregation kinetics compared with controls. An elevation of the
      shear resistance of the aggregates was found for CRP at a concentration of 0.438
      g/l. By an increase in the concentration of Cp from 4.40 to 9.39 g/l, the
      aggregation kinetics and the adhesive forces between erythrocytes were
      significantly increased: No effect on erythrocyte aggregation was observed for
      alpha 1-AGP, alpha 1-AT, and Cp at concentrations of 2.85, 3.97, and 2.43 g/l,
      respectively. The molecular mass of the acute-phase proteins, their
      configuration, and the presence of specific receptors on the erythrocyte membrane
      are postulated as possible factors influencing erythrocyte aggregation.

PMID- 8997293
TI  - Ventilation-induced pulmonary vasodilation at birth is modulated by potassium
      channel activity.
AB  - At birth, pulmonary blood flow rapidly increases 8- to 10-fold, and pulmonary
      arterial pressure falls by 50% within 24 h. The postnatal adaptation of the
      pulmonary circulation is mediated, in part, by endothelium-derived nitric oxide
      (EDNO). Recent studies suggest that EDNO may reduce vascular resistance, in part,
      by activating K+ channels. We hypothesized that K+ channels modulate the changes
      in pulmonary hemodynamics associated with birth. To test this hypothesis, we
      studied the effect of K+ channel inhibition on two separate, but interdependent
      stimuli: 1) mechanical ventilation with low inspired O2 concentrations (designed
      to maintain normal fetal blood gas tensions) and 2) mechanical ventilation with
      high inspired O2 concentrations. Tetraethyl-ammonium (TEA, 1 mg/min for 100 min;
      n = 5), a nonspecific K+ channel blocker, glibenclamide (Gli, 1 mg/min for 30
      min; n = 6), an ATP-sensitive K+ channel blocker, or saline (n = 7) was infused
      into the left pulmonary artery (LPA) of acutely instrumented fetal lambs. The
      umbilical-placental circulation remained intact, and lambs were ventilated with
      0.10 inspired O2 concentration (FIO2) for 60 min, followed by 1.0 FIO2 for 20
      min. Neither TEA nor Gli had an effect on basal pulmonary tone. TEA attenuated
      the increase in LPA flow and decrease in pulmonary vascular resistance in
      response to mechanical ventilation with 0.10 and 1.0 FIO2; Gli had no effect.
      These results support the hypothesis that non-ATP-sensitive K+ channels modulate
      the transition from fetal to neonatal pulmonary circulation.

PMID- 8997294
TI  - Transient outward current in catecholamine-induced cardiac hypertrophy in the
      rat.
AB  - We have demonstrated that a daily injection of isoproterenol (5 mg/kg ip) for 7
      days induces a 30% increment in heart weight-to-body weight ratio and prolongs
      the action potential duration (APD) in male Wistar rats. The underlying mechanism
      of the prolonged APD was investigated in this model of hypertrophy by measuring
      the transient outward potassium current (Ito) in left ventricular myocytes of the
      rat with whole cell voltage-clamp techniques. Cell membrane capacitance was
      increased by 39%: 122 +/- 3 (n = 23) and 171 +/- 5 (SE) pF (n = 20) in control
      and hypertrophy, respectively (P < 0.001). Ito was evoked in sodium-free
      solutions containing 0.5 mM Ca2+ and 2 mM Co2+ by step depolarizations from a
      holding potential of -80 mV. The amplitude of the 4-aminopyridine-sensitive Ito
      (at 70 mV) was reduced by 28% in hypertrophy: 3.2 +/- 0.3 (n = 23) and 2.3 +/-
      0.4 (SE) nA (n = 20) in control and hypertrophy, respectively (P < 0.05). When
      normalized for cell capacitance, the reduction was much larger: 26.4 +/- 2.5 and
      13.1 +/- 1.8 pA/pF in control and hypertrophy, respectively (P < 0.001). The
      voltage dependence of Ito was similar in both cell types. No change was observed
      in the steady-state activation and inactivation kinetics in the two groups, nor
      was there a change in the time dependence of inactivation. The recovery from
      inactivation of Ito when fitted with a monoexponential function was not changed
      significantly in hypertrophy: time constants = 8.2 +/- 0.4 (n = 13) and 8.3 +/-
      0.3 ms (n = 12) in control and hypertrophy, respectively. These results show that
      Ito density is decreased in catecholamine-induced cardiac hypertrophy, but
      current kinetics are not affected. The reduced Ito density may underlie the
      prolongation of APD in this model of hypertrophy.

PMID- 8997295
TI  - Coronary vascular and endothelial reactivity changes in transgenic mice
      overexpressing atrial natriuretic factor.
AB  - Recent advances in genetic methods permit the introduction of random and defined
      mutations into the mouse germ line, producing novel mouse strains, some of which
      affect the heart and vasculature. A TTR-ANF transgenic strain of mice, which
      constitutively expresses a fusion gene consisting of the transthyretin promoter
      and the ANF structural gene, has been shown to result in a lifelong elevation of
      plasma atrial natriuretic factor (ANF) and a chronically lowered arterial blood
      pressure. However, no established method for efficient functional analysis of
      possible alterations in coronary vascular function in mice has been reported. In
      the present study, we describe an isolated mouse coronary artery preparation that
      permits an effective and reproducible evaluation of coronary endothelial and
      vascular function. Both left main and right coronary arteries (resting luminal
      diam 70-90 microns) were isolated and pressurized, and changes in luminal
      diameter were determined by videomicroscopy. The coronary pressure-luminal
      diameter relationship was not significantly different between TTR-ANF transgenic
      and nontransgenic littermates. Relaxation of coronaries to 0.1-100 nM ANF was
      significantly reduced in transgenic [maximum effect (Emax) = 43 +/- 10% (mean +/-
      SE) of 11 vessels] compared with nontransgenic (Emax = 73 +/- 7%, n = 15) mice.
      Similarly, the relaxant response to an endothelium-dependent dilator,
      acetylcholine, but not to endothelium-independent dilators sodium nitroprusside
      and isoproterenol, was significantly decreased in transgenic (Emax = 46 +/- 10%,
      n = 12) compared with nontransgenic (Emax = 85 +/- 5%, n = 14) mice. In contrast,
      the dose-dependent vasoconstriction to endothelin-1, KCl and the thromboxane
      mimetic U-46619 was not significantly different between the two groups. These
      results indicate that lifelong ANF elevation in mice is associated with a
      decreased responsiveness of coronary vasorelaxation to ANF, possibly resulting
      from receptor downregulation and/or desensitization. Endothelium-dependent
      relaxation was also significantly depressed in transgenic mouse coronary
      arteries, but smooth muscle-specific dilation and constriction were not affected.
      The present findings are consistent with previous studies of TTR-ANF transgenic
      mice showing that ANF regulates arterial blood pressure and vascular function.

PMID- 8997297
TI  - Skeletal muscle microvascular and tissue injury after varying durations of
      ischemia.
AB  - The purpose of this study was to examine the effect of varying durations of
      ischemia on several microvascular parameters in the awake hamster chamber model.
      The goal was to characterize the microvascular damage that occurs in skeletal
      muscle as a result of ischemia and reperfusion. The chamber tissues were
      subjected to 1-5 h of ischemia, and then the following parameters were measured:
      vessel diameter, endothelial thickness, macromolecular leakage, red blood cell
      velocity, adherent leukocytes, rolling leukocytes, freely flowing leukocytes,
      functional capillary density, and propidium iodide-positive cell nuclei. In
      control animals there was no significant difference in any parameters over the
      entire observation period. After 1 or 2 h of ischemia an increase in rolling and
      adherent leukocytes was measured. After 3 h of ischemia there was a significant
      increase in the mean endothelial thickness and in the number of nonviable cells.
      After 4 h of ischemia a significant difference in the extent of macromolecular
      leakage and the functional capillary density was additionally observed. After 5 h
      of ischemia this damage was more pronounced and often so severe that
      approximately 50% of the vessels demonstrated no reflow.

PMID- 8997296
TI  - Ca2+ entry through conductive pathway modulates receptor-mediated increase in
      microvessel permeability.
AB  - We investigated the relationship between receptor-mediated increases in
      cytoplasmic Ca2+ concentration ([Ca2+]i) and increased microvessel permeability.
      In individually perfused venular microvessels of frog mesentery exposed to 10
      microM ATP, [Ca2+]i increased from 59 +/- 7 to 172 +/- 21 nM within 1 min and
      then fell back toward control values. The corresponding peak increase in the
      hydraulic conductivity (Lp) of the microvessel wall was 5.7 +/- 0.5-fold relative
      to control. After removal of extracellular Ca2+, there was no significant
      increase in Lp, and the initial increase in [Ca2+]i was attenuated but not
      abolished. Depolarization of the endothelial cell membrane with high-K+ Ringer
      solution reduced the peak increase in [Ca2+]i to 106 +/- 7 nM and attenuated the
      increase in Lp 1.8 +/- 0.4-fold. The results conform to the hypothesis that Ca2+
      entry into endothelial cells is required for acute increase in venular
      microvessel permeability by inflammatory agents and that the pathway for Ca2+
      entry has the properties of a passive conductance pathway. Similar conclusions
      were reached in previous experiments in frog microvessels exposed to Ca2+
      ionophores and perfusates with no plasma proteins. In venular microvessels of
      hamster mesentery exposed to ATP and bradykinin, a similar pathway for Ca2+ entry
      was demonstrated in the present experiments. We did not measure permeability
      changes in hamster microvessels in this study, but these microvessels respond to
      histamine and ionophores with a transient increase in permeability to
      macromolecules similar to that measured in frog microvessels [Am. J. Physiol. 268
      (Heart Circ. Physiol. 37): H1982-H1991, 1995].

PMID- 8997298
TI  - Derivation of the ascending aortic-carotid pressure transfer function with an
      arterial model.
AB  - To devise a method of deriving the ascending aortic pressure waveform from the
      noninvasively determined carotid arterial waveform, ascending aortic and carotid
      arterial pressures were recorded in 13 patients aged 58.5 +/- 10.0 (SD) yr. A
      single viscoelastic tube terminated with a modified windkessel was used to model
      the carotid arterial system. For each patient the model parameters,
      characteristic impedance of the tube (Z0), reflection coefficient at the
      termination (gamma), and time constant of the windkessel (tau), were estimated by
      minimizing the root-mean-square error between the measured and predicted carotid
      waveforms, with the ascending aortic pressure waveform as input. The resulting
      arterial parameters were realistic: Z0 = 729.5 +/- 246.8 dyn.s.cm-3, gamma = 0.75
      +/- 0.19, and tau = 0.16 +/- 0.17 s. A generalized model constructed with these
      mean parameters yielded a smaller error between predicted and measured carotid
      arterial pressures (3.4 +/- 1.3 mmHg) than between ascending aortic pressure and
      measured carotid arterial pressure (4.4 +/- 1.6 mmHg, P < 0.01) and also
      reproduced the carotid wave contour indexed by the ratio of late systolic to
      early systolic peak amplitude: predicted = 1.26 +/- 0.05 and measured = 1.24 +/-
      0.16 vs. aortic = 1.55 +/- 0.19.

PMID- 8997299
TI  - Role of intracellular alkalinization in inhibition of acetylcholine-induced
      relaxation by FMLP in rat aorta.
AB  - N-formylmethionyl-leucyl-phenylalanine (FMLP), a chemotactic tripeptide, is known
      to cause intracellular alkalinization. Moreover, there is a specific receptor for
      FMLP in vascular endothelial cells but not in vascular smooth muscle cells.
      Because we have already reported that intracellular alkalinization inhibits
      acetylcholine (ACh)-induced relaxation, we examined whether FMLP alters the
      vasodilation of endothelial cells through intracellular alkalinization. FMLP
      reduced ACh-induced relaxation in aortic rings from Sprague-Dawley rats but did
      not affect nitroglycerin-induced relaxation. N-t-butoxycarbonyl-phenylalanyl -D
      leucyl-phenylalanyl-D-leucyl-phenylalanine, a specific formyl receptor
      antagonist, reversed the impairment of ACh-induced relaxation, as did the protein
      kinase C inhibitors sphingosine and 1-(5-isoquinolinylsulfonyl)-2
      methylpiperazine (H-7). The sodium/proton antiport inhibitor amiloride and the
      proton ionophore nigericin normalized the attenuated ACh-induced relaxation. FMLP
      induced impairment was normalized by the phospholipase A2 inhibitor quinacrine,
      the cyclooxygenase inhibitor indomethacin, and the antagonists of the
      prostaglandin H2 and/or thromboxane A2 receptor, ONO-3708 and S-1452,
      respectively. Superoxide dismutase inhibited the effect of FMLP. In conclusion,
      FMLP attenuated ACh-induced relaxation, possibly through intracellular
      alkalinization. Increased production of vasoconstrictor prostaglandin(s) and
      superoxide may contribute to the inhibitory effect of FMLP-induced alkalinization
      on ACh-induced relaxation.

PMID- 8997300
TI  - Regional electrical activation and mechanical function in the partially ischemic
      left ventricle of dogs.
AB  - During normoxia, asynchronous electrical activation of the left ventricle
      significantly affects regional mechanical performance. Regional fiber strain and
      external work during the ejection phase are found to be lower in early-activated
      than in late-activated regions. Because electrical activation is known to be
      delayed during ischemia, the present study was designed to investigate the
      influence of this electrical asynchrony on regional fiber strain, if any, during
      moderate and severe myocardial ischemia. Regional electrical activation time
      (t(ea)) and fiber strain during the ejection phase (ef,e) were measured in the
      epicardial layers of the left ventricular anterior wall during normoxia and after
      15 min of total occlusion (n = 5) or 30, 60, 120, and 180 min of partial
      occlusion of the left anterior interventricular coronary artery (LAICA; n = 11).
      Myocardial blood flow (MBF) was assessed with radioactive microspheres. Blood
      gases, pH, and lactate and Pi contents were determined in arterial, local venous,
      and coronary sinus blood. During normoxia, t(ea) and ef,e were similar in various
      epicardial regions of the left ventricular anterior wall. During total LAICA
      occlusion, in the ischemic area, subepicardial MBF decreased from 0.86 +/- 0.36
      (SD) to 0.18 +/- 0.09 ml.g-1.min-1 and subepicardial ef,e decreased from -0.11 +/
      0.02 to -0.01 +/- 0.01, whereas the delay in t(ea) between the normoxic basal
      lateral and ischemic apical-medial areas increased slightly but significantly
      from 1.9 +/- 8.0 to 7.5 +/- 8.0 ms. After a 180-min partial occlusion of the
      LAICA, in the ischemic area, subepicardial MBF decreased from 0.62 +/- 0.17 to
      0.49 +/- 0.18 ml.g-1.min-1 and ef,e decreased from -0.08 +/- 0.01 to -0.03 +/-
      0.01. No significant change in the difference in t(ea) between the normoxic and
      ischemic areas could be detected (5.1 +/- 4.8 and 5.2 +/- 5.8 ms in the control
      situation and after 180-min partial occlusion, respectively). These findings
      indicate that in the ischemic epicardium 1) mechanical function is more affected
      than electrical impulse conduction and 2) delayed activation, if any, is
      accompanied by decreased instead of increased fiber strain, as found in the
      normoxic left ventricle.

PMID- 8997301
TI  - Combined inhibition of P-selectin and ICAM-1 reduces myocardial injury following
      ischemia and reperfusion.
AB  - Neutrophil-endothelial cell interactions are mediated by a number of cell
      adhesion proteins. We investigated the effects of inhibition of P-selectin and
      intercellular adhesion molecule-1 (ICAM-1), individually or in combination, in
      the ischemic-reperfused canine myocardium. Monoclonal antibodies PB1.3 (anti-P
      selectin) and CL 18/6 (anti-ICAM-1) were administered to dogs subjected to
      coronary artery occlusion and reperfusion. After reperfusion, untreated dogs
      experienced a 61% decline (P < 0.01 vs. baseline) in myocardial blood flow and a
      ninefold increase in ischemic zone neutrophil accumulation (4.7 +/- 0.9 U/100 mg
      tissue myeloperoxidase activity). In contrast, PB1.3 and CL 18/6 administered
      individually preserved myocardial blood flow (11 and 24% decrease from baseline,
      respectively, both P < 0.01 vs. saline), and significantly attenuated
      myeloperoxidase activity (1.4 +/- 0.3 and 1.5 +/- 0.26 U/100 mg tissue,
      respectively, both P < 0.01 vs. saline). PB1.3 and CL 18/6 in combination
      resulted in significant coronary vascular and myocardial protection that was not
      superior to treatment with either antibody alone. Thus the coadministration of
      anti-P-selectin and anti-ICAM-1 monoclonal antibodies does not enhance the degree
      of myocardial protection in this model of reperfusion injury.

PMID- 8997302
TI  - Nonspecific inhibition of adenosine-activated K+ current by glibenclamide in
      guinea pig atrial myocytes.
AB  - The ATP-sensitive K+ (KATP) channel blocker glibenclamide was reported to inhibit
      the K+ current activated by adenosine. This study investigated whether the
      inhibition by glibenclamide of the adenosine-induced current is due to a specific
      blockade of KATP channels in guinea pig atrial myocytes. In the absence of
      adenosine, the basal background current was an inward rectifier K+ current (IK1).
      Glibenclamide at concentrations of 10, 30, and 100 microM reduced the basal
      background K+ current by 15 +/- 6, 43 +/- 10, and 63 +/- 11%, respectively. In
      the presence of adenosine (10 microM), glibenclamide (30 microM) decreased the
      adenosine-induced K+ current by 39 +/- 3%. A similar inhibitory effect of
      glibenclamide on the outward K+ currents activated by either the muscarinic
      agonist carbachol or the nonhydrolyzable GTP analogue guanosine 5'-[gamma
      thio]triphosphate was observed. A low concentration (1 microM) of glibenclamide
      did not significantly attenuate the current elicited by adenosine, although it
      completely abolished the outward K+ current activated by pinacidil, a KATP
      channel opener. Thus we conclude that the inhibition of adenosine-induced K+
      current by glibenclamide at high concentrations (> 1 microM) is not due to a
      specific blockade of KATP channels, but rather, resulted from a blockade of IK1.

PMID- 8997303
TI  - Rapid mast cell activation causes leukocyte-dependent and -independent
      permeability alterations.
AB  - The major objective of this study was to systematically elucidate the mechanisms
      underlying microvascular permeability in rat mesenteric venules after the
      activation of perivascular mast cells. Intravital microscopy was used to assess
      polymorphonuclear leukocyte (PMN) infiltration and microvascular permeability
      alterations in single 25- to 40-micron diameter venules. Ruthenium red was used
      to detect mast cell activation on-line. Exposure of mast cells to compound 48/80
      (CMP 48/80) caused a rapid mast cell activation and increase in microvascular
      permeability (within 15 min) that was maintained for the duration of the
      experiment. CMP 48/80 also increased PMN adhesion to the microvascular
      endothelium. Anti-PMN serum, as well as various antiadhesion therapies, including
      CL26 (anti-CD18 antibody) and fucoidan (selectin-immunoneutralizing
      carbohydrate), revealed that the early microvascular permeability was PMN
      independent. However, these regimens significantly reduced plasma protein leakage
      out of venules between 30 and 60 min. Methysergide (serotonin receptor
      antagonist), but not diphenhydramine (histamine receptor antagonist), inhibited
      the early PMN-independent microvascular permeability. Finally, a platelet
      activating factor (PAF)-receptor antagonist did not affect the early phase of
      microvascular permeability but reversed the later phase, consistent with PAF's
      role as a proadhesive molecule for PMN during mast cell activation. These data
      demonstrate that, within the first hour of mast cell activation, a biphasic PMN
      independent and -dependent response in microvascular permeability is observed.
      The data also raise the possibility that histamine's physiological role in this
      model may be unrelated to alterations in microvascular permeability.

PMID- 8997304
TI  - Superoxide and nitroglycerin stimulate release of PGF2 alpha and TxA2 in isolated
      rat heart.
AB  - The aim of this study was to investigate the effects of nitroglycerin (NTG), a
      nitric oxide (NO) donor used as a vasodilating agent, on prostanoid [e.g.,
      prostaglandin (PG)] release in the O2(-)-pretreated rat heart. Perfusion of O2-,
      generated by a xanthine oxidase-purine coupling, caused elevation (P < 0.05) of
      the coronary perfusion pressure (CPP) after 20 min (from 57.1 +/- 3.9 during the
      control period to 72.2 +/- 3.9 mmHg, P < 0.05). O2- caused increased release of
      PGF2 alpha from 3.6 +/- 0.7 to 20.6 +/- 4.4 pmol.min-1.g-1 and of thromboxane A2
      (TxA2) from 2.4 +/- 0.4 to 9.6 +/- 1.6 pmol.min-1.g-1 (P < 0.001) with no
      significant changes in PGE2 and PGI2 release. During the 20-min washout of O2-
      from the heart with normal Krebs solution, release of PGF2 alpha and TxA2
      decreased to 8.7 +/- 1.4 and 6.3 +/- 1.7 pmol.min-1.g-1, respectively, and the
      release of PGE2 and PGI2 markedly increased from 11.1 +/- 2.9 to 25.4 +/- 3.6 and
      157.2 +/- 16.4 to 413.2 +/- 41.4 pmol.min-1.g-1, respectively (P < 0.05), without
      lowering the elevated CPP. Administration of 4 microM NTG during the washout
      period paradoxically augmented the elevated CPP to 133.3 +/- 0.6% and was
      associated with a doubling (P < 0.05) of PGF2 alpha and TxA2 release with no
      significant changes in PGE2 and PGI2 release. The NTG-induced CPP elevation was
      inhibited (P < 0.05) by indomethacin, a cyclooxygenase inhibitor, or ONO-3708, a
      TxA2 receptor blocker, whereas arachidonic acid, a substrate for PG synthesis,
      augmented the CPP elevation. These results indicate that NTG stimulates the
      synthesis of vasoconstrictive PG in the O2(-)-pretreated rat heart, inducing a
      paradoxical elevation in CPP.

PMID- 8997305
TI  - Erythrocyte flow and elasticity of microvessels evaluated by marginal cell-free
      layer and flow resistance.
AB  - Flow dynamics of human erythrocytes was compared in elastic (E) and hardened (H)
      microvessels with inner diameters of 10-40 microns. The thickness of the marginal
      cell-free layer and the overall flow resistance were measured with a vascular bed
      isolated from rabbit mesentery (E vascular bed) as well as with a 4%
      paraformaldehyde-fixed bed (H vascular bed). 1) In both E and H microvessels, the
      thickness of the cell-free layer increased with increasing inner diameter of the
      microvessels and with decreasing hematocrit accompanied by an overall decrease in
      the flow resistance. The hematocrit-dependent change of the cell-free layer
      thickness was greater in the E microvessels than in the H microvessels. The flow
      resistance was always greater in the H vascular beds than in the E vascular beds.
      2) With decreasing erythrocyte deformability induced by treatment with 2 mM
      diazenedicar-boxylic acid bis(N,N-dimethylamide), the thickness of the cell-free
      layer decreased at a low hematocrit in the E microvessels and at a high
      hematocrit in the H microvessels, although the flow resistance was increased in
      both vascular beds. 3) Dextran of 70,400 average molecular weight accelerated the
      formation of the cell-free layer by inducing erythrocyte aggregation. A drastic
      increase in the cell-free layer thickness at 2-4 g/dl of dextran in the E
      microvessels and at 1-2 g/dl of dextran in the H microvessels was accompanied by
      a significantly lower increase in the flow resistance. This study concludes that
      the elasticity of microvessels may play an important role for reducing the
      overall flow resistance of a vascular bed, which is modulated by the marginal
      cell-free layer, itself a function of the rheological properties of the
      erythrocytes.

PMID- 8997307
TI  - Alpha-adrenoceptor activation of a chloride conductance in rat iris arterioles.
AB  - Changes in membrane potential associated with alpha-adrenoceptor-mediated
      contraction of rat iris arterioles after nerve stimulation (10 Hz, 1 s) have been
      measured with conventional intracellular recording techniques. Two different
      types of intracellular responses were recorded. Cells that show a depolarization
      are proposed to represent the arteriolar smooth muscle cells because the
      characteristics of the depolarization are correlated with those of the
      contraction. Cells that show no response or a small hyperpolarization in response
      to nerve stimulation are proposed to represent the endothelial cells of the
      arteriole. Both the depolarization and the contraction were abolished by
      tetrodotoxin (1 microM), benextramine (10 microM), and prazosin (0.1 mM),
      indicating that they result from nerve-mediated activation of alpha
      adrenoceptors. A small but significant part of the contraction (30%) and the
      depolarization (11%) was nifedipine sensitive (10 microM). Caffeine (1 mM)
      abolished the contraction and reduced the depolarization by one-half. Reducing
      the external chloride concentration also abolished the contraction and reduced
      the depolarization by 90%. Flufenamic acid (250 mM) abolished both the
      contraction and the depolarization. It is suggested that, in iris arterioles, the
      activation of synaptic alpha-adrenoceptors leads to the release of intracellular
      calcium that activates both the chloride channels in the cell membrane leading to
      depolarization and the intracellular contractile apparatus leading to
      vasoconstriction.

PMID- 8997306
TI  - ATP-sensitive potassium channels in cultured arterial segments.
AB  - Organ cultures of arteries have been used to study growth responses,
      proliferation, and contractility. However, the function of specific-ion channels
      in cultured arteries has not been investigated. ATP-sensitive K+ (KATP) channels
      play an important role in the control of arterial tone. The goal of this study
      was to determine the functional state of KATP channels in arteries kept in
      culture. Segments from rabbit mesenteric arteries were cultured in for 2-7 days.
      To explore the properties of KATP channels, the effects of KATP-channel
      modulators and other vasoactive substances on isometric force, density, and
      modulation of KATP currents in single smooth muscle cells isolated from cultured
      vessels were examined. Isometric contractions were measured with a resistance
      vessel myograph. Whole cell KATP currents were recorded with the patch-clamp
      technique. Membrane capacitance and KATP-current density in single smooth muscle
      cells from freshly dissected (control) and cultured arteries were not altered. At
      -60 mV, glibenclamide-sensitive currents in the presence of the K(+)-channel
      opener pinacidil were -4.7 +/- 1.2, -4.7 +/- 0.6, and -4.6 +/- 0.7 pA/pF for
      control and 2- and 4-day arteries, respectively. Inhibitory modulation of KATP
      currents in arterial smooth muscle also remained intact for 4 days in culture;
      the vasoconstrictor histamine (10 microM) reduced glibenclamide-sensitive
      currents in the presence of pinacidil by 61.2 +/- 2.8, 42.4 +/- 10.1, and 41.2 +/
      6.1% for control and 2- and 4-day arteries, respectively. Pinacidil relaxed
      control and cultured arteries (1-7 days) in a dose-dependent manner. Half-maximal
      effective concentrations of pinacidil were 0.42, 0.24, 0.23, and 0.51 microM for
      control and 2-, 4-, and 7-day arteries, respectively, whereas maximal relaxations
      to pinacidil were 62.9, 47.5, 37.5, and 55.7% for control and 2-, 5-, and 7-day
      arteries, respectively. Histamine, norepinephrine, and serotonin constricted
      cultured arteries, although responses to histamine and norepinephrine diminished
      by 30-50% after 5 days in culture. The relaxant effect of acetylcholine was not
      maintained in cultured arteries. Sodium nitroprusside, however, effectively
      relaxed arteries cultured for 2-7 days. The data indicate that with the culture
      model described, KATP channels in arterial smooth muscle remained functional and
      contractile responses in arterial segments were maintained for up to 7 days.
      These results suggest that this approach can be used to study either long-term
      regulation of KATP channels or the role of this channel type in growth responses.

PMID- 8997309
TI  - Mechanisms contributing to pulsus alternans in pressure-overload cardiac
      hypertrophy.
AB  - The mechanisms underlying pulsus alternans in pressure-over-load (POL) cardiac
      hypertrophy were investigated. Simultaneous measurements of force and
      intracellular Ca2+ (using fura 2) in right ventricular papillary muscles under
      conditions that produced mechanical alternans, revealed alternation of the
      amplitude of the Ca2+ transient together with alternation of force in some POL
      muscles. Instances when alternation of force occurred without any apparent
      alternation of the Ca2+ transient were also observed. Exposure of muscles to 5
      microM ryanodine significantly attenuated mechanical alternans, thereby
      implicating a role for the sarcoplasmic reticulum (SR) in this process. The time
      course of restitution of force and the intracellular Ca2+ transient were,
      however, unchanged in POL hearts, indicating that SR Ca2+ cycling was not
      appreciably slowed. The fraction of Ca2+ recirculated intracellularly was derived
      from studies of postextrasystolic potentiation and was significantly reduced in
      the POL hearts, suggesting additional differences in cellular Ca2+ regulation. We
      conclude that changes in Ca2+ handling play an important role in the onset of
      mechanical alternans in POL hypertrophy, but that additional factors, most likely
      a slowing of crossbridge cycling rate, are also likely to be important.

PMID- 8997308
TI  - IK of rabbit ventricle is composed of two currents: evidence for IKs.
AB  - The delayed rectifier K+ current (IK) in rabbit heart has long been thought to
      consist of only a single, rapidly activating, dofetilide-sensitive current, IKr.
      However, we find that IK of rabbit ventricular myocytes actually consists of both
      rapid and slow components, IKr and IKs, respectively, that can be isolated
      pharmacologically. Thus, after complete blockade of IKr with dofetilide, the
      remaining current, IKs, is homogeneous as judged by an envelope of tails test.
      IKs activates and deactivates slowly, continues to activate during sustained
      depolarizations, has a half-activation potential of 7.0 +/- 0.8 mV and slope
      factor of 11.0 +/- 0.7 mV, reverses at -77.2 +/- 1.3 mV (extracellular K+
      concentration = 4 mM), is increased by removing extracellular K+, and is enhanced
      by isoproterenol and stocked by azimilide. Northern analysis demonstrates that
      the minK (IsK) gene, which encodes a subunit of the channel that underlies the
      IKs current, is expressed in rabbit heart. Expression of the rabbit protein in
      Xenopus oocytes elicits a slowly activating, voltage-dependent current, IsK,
      similar to those expressed previously from mouse, rat, guinea pig, and human
      genes. The results demonstrate that IKs is present in rabbit ventricle and
      therefore contributes to cardiac repolarization in this species.

PMID- 8997310
TI  - Characterization of the effects of histamine in porcine tracheobronchial lymph
      vessels.
AB  - We characterized the responses of lymphatic vascular smooth muscle to
      histaminergic-receptor stimulation and blockade and explored the mechanisms
      underlying the histamine-stimulated release of endothelium-derived relaxing
      factor (EDRF). Fresh porcine tracheobronchial lymph vessel rings mounted in organ
      baths were stimulated by the cumulative addition of histamine or H1, H2, and H3
      receptor-specific agonists in the presence or absence of receptor-specific
      antagonists. Histamine had a contractile effect on lymphatic vascular smooth
      muscle that was H1 receptor mediated. No important effects were elicited by H2-
      or H3-receptor stimulation. Histamine also caused the release of EDRF as
      demonstrated by an increase in smooth muscle tone in the absence of endothelium
      and after inhibition of nitric oxide synthase. This effect was strong at high
      concentrations of histamine and was mediated by H1-receptor stimulation. The
      results suggest that histamine may contribute to the regulation of lymphatic
      vascular smooth muscle tone under pathological conditions, an effect that may be
      controlled through modification of H1-receptor activity.

PMID- 8997311
TI  - Oxidized low-density lipoproteins and microvascular responses to ischemia
      reperfusion.
AB  - The objective of this study was to determine whether ischemia and reperfusion
      (I/R) and/or chronic arterial hypertension potentiates the leukocyte-endothelial
      cell adhesion (LECA) and microvascular dysfunction elicited by oxidized low
      density lipoproteins (ox-LDL). Mast cell degranulation, leukocyte adherence and
      emigration, and albumin leakage were monitored in postcapillary venules of rat
      mesentery. Intra-arterial infusion of copper-oxidized LDL (Cu-LDL), at a
      concentration that does not directly affect the microvasculature, significantly
      enhanced the I/R-induced recruitment of adherent and emigrated leukocytes but
      does not affect the increased albumin leakage and mast cell degranulation
      responses normally observed after I/R. Infusion of a higher concentration of Cu
      LDL in nonischemic mesentery of either normotensive Wistar-Kyoto or spontaneously
      hypertensive rats elicited significant yet similar increases in LECA, mast cell
      degranulation, and albumin leakage. These findings indicate that 1) ox-LDL act
      synergistically with I/R to promote leukocyte recruitment in postcapillary
      venules but without an accompanying exacerbation of albumin leakage, and 2) ox
      LDL do not elicit a more intense inflammatory response in the microvasculature of
      hypertensive versus normotensive animals.

PMID- 8997312
TI  - Protection of ischemic myocardium by inhibition of contracture in isolated rat
      heart.
AB  - Protection of the ischemic myocardium by pretreatment with a high dose of 2,3
      butanedione monoxime (BDM) is attributed to the enhancement of glycolytic ATP
      production rather than to the inhibition of contracture during mild ischemia. Our
      objective was to investigate whether the inhibition of contracture would protect
      the arrested heart during prolonged ischemia. Isolated perfused rat hearts were
      subjected to 30 min of low-flow ischemia followed by reperfusion. Ischemic hearts
      were treated with BDM (5 mmol/l) after beating stopped. BDM ameliorated the
      increase in intraventricular pressure after ischemia without significant changes
      in ATP levels and with a decreased accumulation of lactate. BDM treatment
      accelerated the recovery of function and high-energy phosphates with reduced
      myocardial Ca2+ overload. The results of this study suggested that inhibition of
      contracture can protect the heart from ischemia-reperfusion injury.

PMID- 8997313
TI  - Vascular endothelial growth factor increases hydraulic conductivity of isolated
      perfused microvessels.
AB  - These experiments report the first direct measurement of microvessel permeability
      coefficients after exposure to vascular endothelial growth factor (VEGF). The
      Landis technique was extended to enable measurement of the resistance of the
      microvessel wall to water flow, hydraulic conductivity (Lp), on the same
      microvessel in the frog mesentery during the initial exposure to VEGF (acute) and
      24 and 72 h after initial exposure (chronic). Control measurements of Lp showed
      no change either acutely or chronically. Exposure to 1 nM VEGF rapidly and
      transiently increased microvessel Lp within 30 s (to 7.8-fold greater than
      baseline values) and returned to control within 2 min. The baseline Lp was
      fivefold greater after 24 h than the initial baseline as a result of VEGF
      perfusion and returned to its original value after 72 h. These experiments
      confirm the hypothesis that VEGF acts both acutely (over a period of a few
      minutes) and chronically (over a few hours) to increase microvascular
      permeability.

PMID- 8997314
TI  - HSP induction inhibits iNOS mRNA expression and attenuates hypotension in
      endotoxin-challenged rats.
AB  - Endotoxin (lipopolysaccharide, LPS)-induced hypotension is, in part, mediated via
      induction of nitric oxide synthase (iNOS), release of nitric oxide, and
      suppression of vascular reactivity (vasoplegia). Induction of heat shock proteins
      (HSP) or inhibition of iNOS expression improves survival in LPS-challenged
      rodents. We studied the effect of induction of HSP on LPS-mediated iNOS
      expression and on LPS-induced vasoplegia and hypotension. Rats were treated with
      the HSP inducer sodium arsenite (6 mg/kg iv) or saline control. Seventeen hours
      later, rats were challenged intravenously with 10 mg/kg of Escherichia coli LPS
      O127:B8 or saline control. Arsenite pretreatment resulted in expression of HSP 70
      mRNA and of HSP 70 and heme oxygenase-1 proteins, inhibition of LPS-mediated iNOS
      mRNA induction, reversal of the LPS-induced hyporesponsiveness to norepinephrine
      ex vivo in isolated mesenteric arteries, and attenuation of LPS-induced
      hypotension in vivo. Our data suggest that induction of HSP expression protects
      rats from LPS by blocking LPS-induced iNOS expression, leading to inhibition of
      the overproduction of nitric oxide and thereby reversing LPS-induced vasoplegia
      and LPS-induced hypotension.

PMID- 8997316
TI  - Permeability-related changes revealed at endothelial cell borders in inflamed
      venules by lectin binding.
AB  - Plasma leakage in inflammation results from intercellular gaps that form in the
      endothelium of venules. These gaps and related morphological changes in
      endothelial cells are not readily seen by light microscopy. In this study we
      sought to visualize such changes by using the selective binding properties of
      plant lectins. Acute inflammation was induced in the trachea of pathogen-free
      F344 rats by injecting substance P intravenously, and 1, 3, or 10 min later the
      vasculature was perfused with fixative followed by a biotinylated lectin. Lectin
      binding was localized by avidinbiotin complex-peroxidase histochemistry and
      viewed in tracheal whole mounts by differential-interference contrast microscopy.
      The binding patterns of the 20 lectins tested fell into 4 groups. Most of the
      lectins either bound uniformly to the endothelium of normal and inflamed venules
      (group 1, e.g., Lycopersicon esculentum lectin) or bound weakly or not at all to
      venules (group 2, e.g., Maackia amurensis I lectin). The uniform binding of group
      1 lectins not only revealed the overall vascular architecture but also made
      visible intercellular gaps and fingerlike processes at endothelial cell borders
      in inflamed venules. In postcapillary venules after substance P, the fingerlike
      processes were present along an average of 32% of the endothelial cell perimeter
      at 1 min, 25% at 3 min, and 7% at 10 min, compared with a baseline value of 2%. A
      third group of lectins (group 3, e.g., concanavalin A) bound selectively to focal
      patches of inflamed venules but bound weakly to normal venules. The fourth group
      (group 4, e.g., Ricinus communis I lectin) bound preferentially to focal patches
      in inflamed venules and also bound uniformly to normal venules. The focal binding
      of group 3 and 4 lectins coincided with sites of plasma leakage marked by
      extravasation of the particulate tracer monastral blue and was associated with
      subendothelial components of the vessel wall. We conclude that selected lectins
      reveal novel features of focal sites of plasma leakage, endothelial gaps, and
      fingerlike processes at endothelial cell borders in inflamed venules.

PMID- 8997315
TI  - Transmembrane potential changes caused by shocks in guinea pig papillary muscle.
AB  - To study transmembrane potential (Vm) changes (delta Vm) caused by extracellular
      field stimulation, Vm was recorded in 10 guinea pig papillary muscles by a double
      barrel microelectrode. A 10-ms shock was delivered during the action potential
      plateau or during diastole. Six shock strengths (1.8 +/- 0.4, 3.8 +/- 0.7, 5.6 +/
      0.9, 7.2 +/- 1.1, 11.1 +/- 1.9, and 17.8 +/- 1.5 V/cm) were given with both
      polarities. The tissue was then treated with either 30 microM tetrodotoxin (TTX;
      n = 5) or 30 microM TTX plus Ca(2+)-free (n = 5) perfusion. For shocks during the
      action potential plateau, delta Vm caused by the six potential gradients was 22.4
      +/- 9.6, 43.6 +/- 17.4, 54.7 +/- 17.9, 60.4 +/- 18.1, 65.4 +/- 13.7, and 66.4 +/-
      12.2 mV for shocks causing depolarization and 41.1 +/- 16.5, 68.3 +/- 22, 80.5 +/
      20.4, 84.0 +/- 19.5, 93.6 +/- 16.3, and 98.9 +/- 15.4 mV for shocks causing
      hyperpolarization. The relationship between delta Vm and shock potential gradient
      was not linear. During diastole, hyperpolarizing shocks induced initial
      hyperpolarization, then depolarization followed again by hyperpolarization. A new
      depolarization upstroke occurred immediately after the shock. After TTX or TTX
      plus Ca(2+)-free perfusion, point stimuli 10 times diastolic threshold could not
      induce an action potential, but a shock field of 1.8 +/- 0.2 V/cm still induced
      action potentials. The peak value of depolarization measured with respect to
      resting potential (-87 +/- 5 mV) during the hyperpolarizing shock decreased from
      +14 +/- 22 before to -66 +/- 30 mV with TTX perfusion (P < 0.01). The fast
      upstroke rate of depolarization both during and immediately after the end of
      hyperpolarizing shocks was inhibited by TTX perfusion. Thus 1) the relationship
      between delta Vm and shock potential gradient is not linear; 2) field but not
      point stimulation can induce an action potential when Na+ channels are
      inactivated; and 3) during diastole Na+ channels are activated twice by a 10-ms
      hyperpolarizing shock, once during shock-induced hyperpolarization and again
      immediately after the end of the shock.

PMID- 8997317
TI  - Frequency and amplitude of sympathetic discharges by baroreflexes during hypoxia
      in conscious rabbits.
AB  - Sympathetic nerve activity (SNA) from multifiber preparations exhibits two
      distinct components: the frequency at which discharges occur and their relative
      amplitude (reflecting the number of activated nerve fibers within each burst).
      These two components may respond independently to various afferent inputs,
      indicating separate central controlling processes. We examined the response in
      the frequency and amplitude of renal SNA to changes in baroreceptor activity and
      the effect of two forms of hypoxia on this relationship in nine conscious
      rabbits. Rabbits breathed either room air or one of two hypoxic gas mixtures (10%
      O2 or 10% O2 + 3% CO2) for 20 min, during which baroreflexes were stimulated by
      ramp increases and then decreases in arterial pressure with phenylephrine (0.5
      mg/ml iv) and nitroprusside (1 mg/ml) (total arterial pressure range induced was
      80 mmHg). Hypoxia with 10% O2 significantly increased the resting frequency of
      SNA before baroreflex modifications from 2.15 +/- 0.18 to 2.82 +/- 0.25
      discharges/s and with 10% O2 + 3% CO2 to 3.20 +/- 21 discharges/s. The amplitude
      of sympathetic discharges was increased 44 +/- 5% over control levels during 10%
      O2 but was not further increased by the addition of 3% CO2. The baroreflex curve
      for total SNA (1-s averages of the integrated neurogram) showed a graded response
      to the two hypoxic stimuli, with significant increases in the upper plateau,
      gain, and resting point on the curves. However, the baroreflex curve for the
      frequency or amplitude of sympathetic discharges did not show graded responses to
      each hypoxic treatment. The frequency baroreflex curve was sigmoidal and not
      changed from air during 10% O2. During 10% O2 + 3% CO2, the gain (responsiveness)
      of the curve was increased although the range of frequencies occurring was
      unaltered. The baroreflex curve for the amplitude showed similar responses to the
      two hypoxic stimuli, namely, increases in the upper plateau, gain, and resting
      point of the curve. We conclude that the frequency and amplitude of sympathetic
      discharges are able to respond differentially to changes in afferent stimuli.
      Given that alterations in the frequency and recruitment of sympathetic fibers
      (amplitude) to the kidney may have differing effects, this phenomenon may provide
      a previously unknown level of renal hemodynamic control through the interaction
      of specific afferent inputs to the central nervous system.

PMID- 8997318
TI  - Effects of pressure- or volume-overload hypertrophy on passive stiffness in
      isolated adult cardiac muscle cells.
AB  - It has been hypothesized that the changes in myocardial stiffness induced by
      chronic hemodynamic overloading are dependent on changes in the passive stiffness
      of the cardiac muscle cell (cardiocyte). However, no previous studies have
      examined the passive constitutive properties of cardiocytes isolated from animals
      with myocardial hypertrophy. Accordingly, changes in relative passive stiffness
      of cardiocytes isolated from animals with chronic pressure- or volume-overload
      hypertrophy were determined by examining the effects of anisosmotic stress on
      cardiocyte size. Anisosmotic stress was produced by altering superfusate
      osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult
      cats with right ventricular (RV) pressure-overload hypertrophy induced by
      pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload
      hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular
      (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same
      animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5
      mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no
      significant differences between hypertrophied RV and normal LV cardiocytes in
      pressure overload PAB cats with respect to percent change in cardiocyte area (47
      +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in
      LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length
      (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant
      differences in cardiocyte strain between hypertrophied RV and normal LV
      cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy
      and chronic volume-overload hypertrophy did not alter the cardiocyte response to
      anisosmotic stress. Thus chronic overload hypertrophy did not alter relative
      passive cardiocyte stiffness.

PMID- 8997319
TI  - Beating affects the posttranscriptional regulation of alpha-myosin mRNA in
      cardiac cultures.
AB  - Contractile arrest of cardiac myocytes results in increased abundance of alpha
      myosin heavy chain (MHC) mRNA but decreased alpha-MHC protein content. Our aim is
      to determine the posttranscriptional mechanisms regulating alpha-MHC mRNA-protein
      uncoupling in cultured neonatal rat hearts during altered contractile activity.
      Spontaneously contracting myocytes were arrested by the use of verapamil (10
      mumol/l; a Ca(2+)-channel blocker) or by 2,3-butanedione monoxime (5 mmol/l; a
      cross-bridge inhibitor). Inhibition of transcription with amanitin (0.5 mumol/l)
      decreased the alpha-MHC mRNA in normally beating myocytes to a minimal baseline.
      However, the alpha-MHC mRNA did not fall this low in amanitin-treated nonbeating
      myocytes. Concurrently, the alpha-MHC mRNA shifted toward a heavier polysome
      complex when beating was blocked. Together, these data suggest that contractile
      arrest regulates alpha-MHC mRNA abundance posttranscriptionally by stabilizing
      the message at the elongation phase of translation. These posttranscriptional
      regulatory steps are dependent on beating itself and are independent of Ca2+
      entry.

PMID- 8997320
TI  - ANG II chronically supports renal and lumbar sympathetic activity in sodium
      deprived, conscious rats.
AB  - The hypothesis that chronic elevations in endogenous angiotensin II (ANG II)
      increase sympathetic outflow in conscious, normotensive rats was tested by
      determining if acute blockade of ANG II receptors with losartan (10 mg/kg iv)
      decreases renal sympathetic nerve activity (RSNA), lumbar sympathetic nerve
      activity (LSNA), or heart rate (HR) more in rats with higher ANG II levels due to
      a low sodium (LS) diet compared with a control sodium (CS) or high sodium (HS)
      diet. In LS rats, losartan decreased (P < 0.05) mean arterial pressure (MAP) in
      two phases: an immediate decrease of 23 +/- 2 mmHg and a slower fall to 35 +/- 4
      mmHg below control 40 min postlosartan. Five minutes after losartan, RSNA (149 +/
      13%), LSNA (143 +/- 5%), and HR (109 +/- 2%) were increased (P < 0.05). Despite
      further falls in MAP, the elevation in RSNA and HR remained constant, and LSNA
      decreased toward control (119 +/- 4%). After restoration of MAP to basal levels
      with methoxamine or phenylephrine infusion, RSNA (46 +/- 8%), LSNA (49 +/- 11%),
      and HR (76 +/- 2%) were suppressed (P < 0.05). In CS rats, losartan also
      initially decreased (P < 0.05) MAP by 6 +/- 2 mmHg and increased (P < 0.05) RSNA
      to 129 +/- 13%. When MAP was returned to control, RSNA was decreased (70 +/- 8%;
      P < 0.05) but less than in LS rats. In contrast, no changes in MAP, RSNA, LSNA,
      or HR were observed after losartan in HS rats. In conclusion, endogenous ANG II
      chronically supports RSNA, LSNA, and HR in conscious, normotensive low and normal
      sodium intake rats.

PMID- 8997321
TI  - Chronic exercise enhances cardiac alpha 1-adrenergic inotropic responsiveness in
      rats with mild hypertension.
AB  - The singular and combined effects of mild renovascular hypertension (HTN) and
      chronic exercise on the contractile responsiveness of the heart to alpha 1
      adrenergic receptor (alpha 1-AR) stimulation were determined. Age-matched
      normotensive and HTN male Fischer-344 rats were assigned to sedentary control or
      treadmill training groups. Left ventricular (LV) contractile performance was
      assessed by utilizing a modified isovolumic heart preparation at varying
      concentrations of phenylephrine (PE). Groups studied were normotensive sedentary
      (NSD), hypertensive sedentary (HSD), normotensive trained (NTR), and hypertensive
      trained (HTR). PE elicited increases in LV developed pressure (delta P), LV
      maximal rate of pressure development (dP/dt(max)), and LV dP/dt(max)/delta P in
      all experimental groups in a dose-dependent fashion. These PE-induced effects
      were representative of alpha 1-AR-mediated responses because they were observed
      in the presence of beta-adrenoceptor blockade with propranolol. Relative to NSD,
      the effects of PE on contractile function were attenuated in HSD and augmented in
      NTR and HTR hearts. The strength of extrasystolic contractions elicited by the
      delivery of a 300-ms extrasystolic interval at each of three different pacing
      frequencies (240, 270, and 300 beats/min) was greater in NTR and HTR and
      significantly reduced in HSD compared with NSD. Scatchard analysis of
      [3H]prazosin binding was used to assess alpha 1-AR number in myocardium isolated
      from each experimental group. Across all groups, a significant correlation was
      found between alpha 1-AR number and the inotropic responsiveness of the heart to
      PE stimulation. Collectively, these data provide evidence that mild HTN
      diminishes while training augments the inotropic responsiveness of the heart to
      alpha 1-AR stimulation. In addition, training appears to attenuate the adverse
      effects of mild HTN on the alpha 1-AR contractile responsiveness of the
      myocardium.

PMID- 8997323
TI  - Cellular basis for burn-mediated cardiac dysfunction in adult rabbits.
AB  - We have shown that cutaneous burn injury impairs cardiac contractile performance;
      however, the mechanisms remain unclear. In this study, New Zealand White rabbits
      were anesthetized with isoflurane, given a full-thickness scald burn over 30% of
      total body surface area, and resuscitated with lactated Ringer solution (4 ml.kg
      1.%burn-1 for 24 h); rabbits handled in an identical fashion were given a sham
      burn. Serum obtained from burned and control (sham-burned) rabbits was aliquoted
      and frozen at -70 degrees C until assay. Polymorphonuclear neutrophils (PMN) were
      isolated 24 h postburn from both sham and burned rabbits to yield preparations
      with > 95% PMN with > 95% viability. Cardiac myocytes were isolated by retrograde
      perfusion of hearts with Ca(2+)-free collagenase-Tyrode buffer, suspended in
      Krebs-Henseleit buffer containing 10% fetal bovine serum and 1.8 mM Ca2+, and
      incubated (1 x 10(5) cells/well) in a CO2 incubator under several experimental
      conditions, including buffer alone, buffer plus 10% burn serum, buffer plus 10%
      sham serum, or buffer plus either burn or sham PMN (25 x 10(5) cells/well).
      Myocyte viability (%) and creatine kinase (CK; units.ml-1.10(5) cells-1) were
      unchanged after incubation with sham plasma or sham PMN. Incubation of sham
      myocytes with burn plasma caused viability to fall (from 79 +/- 3 to 54 +/- 4%, P
      < 0.002), whereas CK rose (from 1,639 +/- 115 to 2,803 +/- 132 units.ml-1.10(5)
      cells-1, P < 0.01). Similarly, incubation of sham myocytes with burn PMN reduced
      viability (from 83 +/- 2 to 50 +/- 3%, P < 0.01), whereas CK remained unchanged
      (1,880 +/- 168 units.ml-1.10(5) cells-1). Our data indicate that circulating
      myocardial depressant factors after burn injury contribute to cardiac myocyte
      injury.

PMID- 8997322
TI  - Firing properties of identified parasympathetic cardiac neurons in nucleus
      ambiguus.
AB  - This study tests the hypothesis that identified parasympathetic cardiac neurons
      in the nucleus ambiguus possess pacemaker-like activity or, alternatively, that
      these neurons are inherently silent. To test this hypothesis and to examine the
      firing properties of these neurons, parasympathetic cardiac neurons were
      identified by the presence of a fluorescent tracer previously applied to their
      terminals surrounding the heart. Perforated patch-clamp electrophysiological
      techniques were used to study the spontaneous and depolarization-evoked firing
      patterns of these identified parasympathetic cardiac neurons in an in vitro brain
      stem slice. Parasympathetic cardiac neurons were silent. On injection of
      depolarizing current, however, these neurons fired with both little delay and
      spike frequency adaptation. Hyperpolarizing prepulses elicited a significant
      delay before depolarization-evoked firing The Ca(2+)-activated K+ channel blocker
      apamin, but not charybdotoxin, increased the depolarization-activated firing
      frequency of these neurons and inhibited the afterhyperpolarization. In summary,
      parasympathetic cardiac neurons do not have pacemaker-like properties, but they
      do possess discharge characteristics that would enable them to closely follow
      excitatory synaptic activation for prolonged periods.

PMID- 8997324
TI  - Adenosine inhibits leukocyte-induced vasoconstriction.
AB  - Polymorphonuclear leukocytes (PMNs) can induce endothelium-dependent constriction
      of vascular rings. Because adenosine inhibits the function of PMNs, we examined
      the effects of adenosine on the PMN-induced coronary vasoconstriction. We
      measured changes in the isometric tension of isolated rings of canine coronary
      arteries suspended in an organ chamber filled with Krebs-Henseleit solution after
      the addition of autologous PMNs. N-formyl-L-methionyl-leucyl-phenylalanine (FMLP)
      stimulated PMNs increased the tension of the coronary artery with the endothelium
      in a concentration-dependent manner. Treatment of FMLP-stimulated PMNs with
      adenosine inhibited both the adhesion of PMNs to the endothelium and the PMN
      induced vasoconstriction. Stimulation of PMNs with CGS-21680C, but not with
      cyclohexyladenosine, inhibited both the adhesion of PMNs to the endothelium and
      the PMN-induced vasoconstriction. However, treatment of coronary arteries with
      adenosine had no effect on the adherence of PMNs to the endothelium and the PMN
      induced constriction. These results suggest that stimulation of adenosine A2a
      receptors on PMNs may inhibit the PMN-induced vasoconstriction by inhibiting the
      adhesion of PMNs to the endothelium.

PMID- 8997325
TI  - Exogenous effects and endogenous production of endothelin in cardiac myocytes:
      potential significance in heart failure.
AB  - Increased plasma concentrations of endothelin have been identified in patients
      and animals with severe congestive heart failure (CHF). However, whether and to
      what extent increased endothelin (ET) concentrations influence left ventricular
      (LV) myocyte contractility, ET-receptor subtype density, and endogenous ET
      production with the development of CHF remains unclear. Accordingly, myocyte
      contractile function, response to ET, sarcolemmal ET-receptor density, and
      myocyte ET production were examined in pigs following the development of pacing
      induced CHF (240 beats/min, 3 wk, n = 8) and in controls (n = 8). With CHF,
      plasma ET increased over threefold. In the presence of ET (10-500 pM), myocyte
      contractility increased in a dose-dependent manner in control myocytes but
      decreased in CHF myocytes. For example, in the presence of 200 pM ET, velocity of
      shortening increased by 32.8 +/- 2.3 microns/s in controls but decreased by 8.3
      +/- 2.2 microns/s with CHF. LV sarcolemmal ET-receptor density was primarily of
      the ETA-receptor subtype in controls (96 +/- 1.0%) and was unchanged with CHF. In
      quiescent myocyte preparations, control myocytes secreted ET (2.29 +/- 0.45
      amol.cell-1.h-1), which was similar in CHF myocytes. These findings suggest that
      the production of ET may have important and potentially differential effects on
      contractile function with the development of CHF.

PMID- 8997326
TI  - Role of nitric oxide and cGMP system in regulation of ductus arteriosus tone in
      ovine fetus.
AB  - Although endogenous nitric oxide (NO) modulates basal tone in the fetal pulmonary
      and systemic circulations, little is known about its role in regulating ductus
      arteriosus (DA) tone. Immunostaining of DA tissue from late-gestation fetal lambs
      demonstrated strong staining for endothelial NO synthase (eNOS) in DA
      endothelium. To study the physiological role of the NO and guanosine 3',5'-cyclic
      monophosphate (cGMP) system in the DA in vivo, we measured the hemodynamic
      effects of NG-nitro-L-arginine (L-NNA; 30 mg), a NOS inhibitor, methylene blue
      (40 mg), a guanylate cyclase inhibitor, and indomethacin (0.8 mg), a
      cyclooxygenase inhibitor, in 10 chronically prepared late-gestation fetal lambs.
      L-NNA increased main pulmonary artery (MPA) and aortic pressures (P < 0.05 vs.
      baseline) but did not change the pressure gradient between the MPA and the aorta.
      L-NNA caused a small decrease in DA flow and a slight rise in resistance across
      the DA. Methylene blue increased both MPA pressure and the pressure gradient
      between the MPA and the aorta from 0.3 +/- 0.2 (baseline) to 7.0 +/- 2.7 mmHg (P
      < 0.05). Indomethacin increased both MPA pressure and the pressure gradient
      between the MPA and the aorta from 1.1 +/- 0.4 (baseline) to 6.3 +/- 1.5 mmHg (P
      < 0.05) after 40 min. Indomethacin decreased DA flow and increased DA resistance.
      We conclude that eNOS is in fetal DA endothelial cells and that NOS inhibition
      causes constriction of the DA in vivo. DA constriction after NOS inhibition is
      minimal, especially in comparison with cyclooxygenase inhibition. Methylene blue
      also constricts the DA, suggesting that guanylate cyclase activity contributes to
      DA relaxation. We speculate that, although the NO and cGMP system modulates DA
      tone, prostaglandins may play a greater role.

PMID- 8997327
TI  - Inhibition of nitric oxide synthase augments myocardial contractile responses to
      beta-adrenergic stimulation.
AB  - Recent in vitro evidence suggests a role for nitric oxide (NO) in the modulation
      of myocardial contractility. The specific role of NO in the control of cardiac
      function in vivo, however, remains unclear. We investigated the effect of NO
      synthase (NOS) inhibition on myocardial contractility in response to beta
      adrenergic stimulation in autonomically blocked dogs. Intracoronary infusions of
      dobutamine (1-50 micrograms/min) and isoproterenol (0.1 and 0.5 microgram/min)
      were performed before and after the intracoronary administration of the specific
      NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Intracoronary dobutamine
      resulted in a dose-dependent increase in peak first derivative of pressure
      (dP/dtmax) to a maximum of 195 +/- 10% (P < 0.001). After inhibition of NOS with
      intracoronary L-NAME at rates of 0.1 and 1 mg/min, the response to dobutamine was
      significantly enhanced with dP/dtmax, increasing 276 +/- 17 and 317 +/- 26%,
      respectively (P < 0.001). Intracoronary isoproterenol resulted in a maximum
      increase in dP/dtmax of 116 +/- 15% (P < 0.001) that further increased to 154 +/-
      17 and 157 +/- 18% after NOS inhibition with 0.1 and 1 mg/min L-NAME,
      respectively (both P < 0.002). L-NAME had no effect on baseline dP/dtmax but did
      produce a reduction in myocardial guanosine 3',5'-cyclic monophosphate content.
      These results suggest a role for NO in the control of myocardial contractility in
      response to beta-adrenergic stimulation in vivo.

PMID- 8997328
TI  - Effects of leukocyte capillary plugging in skeletal muscle ischemia-reperfusion
      injury.
AB  - The purpose of this study was to examine the relationship between increased
      capillary network resistance due to leukocyte capillary plugging and tissue
      injury following ischemia-reperfusion (I/R). After a 30-min complete ischemia in
      rat spinotrapezius muscle, the frequency and duration of leukocyte capillary
      plugging were measured throughout capillary networks and used to estimate the
      increase in network flow resistance for I/R alone, I/R with phalloidin (Pl), and
      I/R with both Pl and cytochalasin D. Propidium iodide (PI) was used to label
      nonviable muscle cell nuclei within the volume of tissue supplied by the
      capillary network, and counts were made before ischemia, immediately after
      reperfusion, and 1 h postreperfusion. For I/R alone and I/R + Pl there is a
      linear correlation between the increase in resistance (up to 29%) and the
      increase in the number of PI-positive nuclei during the reperfusion period. With
      both Pl and cytochalasin D present in the superfusate, the resistance increase
      was abolished and the amount of tissue damage during reperfusion was minimized.
      The results indicate that the increase in resistance is linearly related to the
      tissue damage and that a reduction of the leukocyte stiffness reduces the injury.

PMID- 8997329
TI  - Comparison of linear and nonlinear formulations of the three-element windkessel
      model.
AB  - The three-element windkessel model incorporating a constant compliance (model A)
      was compared with two nonlinear versions of the same model (models B1 and B2)
      incorporating a pressure-dependent compliance. The aim was to test whether
      nonlinear elasticity yielded better model behavior in describing ascending aortic
      pressure-flow relationships and interpreting the physical properties of the
      arterial system. Exponential and bell-shaped compliance vs. pressure curves were
      assumed in models B1 and B2, respectively. To test these models, we used
      measurements of ascending aortic pressure and flow from three dogs under a wide
      variety of hemodynamic states obtained by administering vasoactive drugs and by
      pacing the heart. These data involved pressure waves with and without an evident
      oscillation during diastole. Model parameters were estimated by fitting
      experimental and model-predicted ascending aortic pressures. Our results
      indicated that only models A and B1 were identifiable. Fits to ascending aortic
      pressure obtained from model B1 were significantly better than fits obtained from
      model A. However, 1) the accuracy of parameter estimates, as judged from
      parameter estimation error analysis, was better in model A than in model B1, 2)
      the estimates of characteristic parameters of the compliance vs. pressure
      relation in model B1 were inconsistent with expected physiological trends of this
      relation, and 3) model B1 did not improve the approximation of diastolic pressure
      in the presence of an evident oscillation. We conclude that, even in the presence
      of better data fit, the nonlinear three-element windkessel cannot be preferred
      over the traditional linear version of this model.

PMID- 8997331
TI  - Right ventricular midwall surface motion and deformation using magnetic resonance
      tagging.
AB  - We describe a method for reconstructing the three-dimensional motion and
      deformation of the midwall surface of the right ventricular free wall (RVFW)
      using magnetic resonance tissue tagging. Tag points were defined where the tag
      stripes intersected the midwall contour and were tracked through systole in both
      short- and long-axis images. A finite-element model of the midwall surface of the
      RVFW was constructed to fit the midwall shape at end diastole. The model was then
      deformed to each subsequent frame by fitting the tag displacements and midwall
      contour locations. The method was applied to two human studies, a normal subject
      and a patient with right ventricular hypertrophy. The root mean squared error
      between model tag planes and tracked tag points was 0.70 mm for the normal heart
      (180 points) and 0.67 mm for the hypertrophic heart (52 points), both less than
      the image pixel size of approximately 1.0 mm. The differences in contraction
      patterns were visualized between the two studies. We conclude that this method
      allows accurate, noninvasive measurement of in vivo RVFW deformation.

PMID- 8997330
TI  - Unstable radii in muscular blood vessels.
AB  - A model of a muscular blood vessel in equilibrium that predicts stable and
      unstable control of radius is presented. The equilibrium wall tension is modeled
      as the sum of a passive exponential function of radius and an active parabolic
      function of radius. The magnitude of the active tension is varied to simulate the
      variable level of smooth muscle activation. This tension-radius relationship is
      then converted to an equilibrium pressure-radius relationship via Laplace's law.
      This model predicts the traditional ability to control the radius below a
      critical level of activation. However, when the active tension is raised above
      this critical level, the pressure-radius relationship (with pressure plotted on
      the ordinate and radius on the abscissa) becomes N shaped with a relative maximal
      pressure (Pmax) and a relative minimal pressure (Pmin). For this N-shaped curve,
      there are three equilibrium radii for any pressure between Pmin and Pmax.
      Analysis shows that the middle radius is unstable and thus cannot be maintained
      at equilibrium. Previously unexplained experimental data reveal evidence of this
      instability.

PMID- 8997332
TI  - Three-dimensional changes in left and right ventricular geometry in chronic
      mitral regurgitation.
AB  - Regional three-dimensional (3-D) right (RV) and left ventricular (LV) geometry
      was studied in eight dogs before and 5-6 mo after induction of mitral
      regurgitation (MR). Ventricular shape changes were quantified with a 3-D finite
      element model fitted to chamber contours traced on cardiac magnetic resonance
      images. MR increased LV end-diastolic volume (LVEDV; 99 vs. 57 ml; P < 0.001) and
      LV stroke volume (LVSV; 55 vs. 26 ml; P < 0.001). In contrast, RVEDV decreased
      (45 vs. 55 ml; P < 0.01), whereas SV was maintained. LV mass (free wall plus
      septum) increased (115 vs. 94 g; P < 0.05), whereas RV free-wall mass was
      relatively unchanged. Shape changes due to MR were characterized by a marked (7.4
      mm) rightward shift of the septum relative to the lateral LV free wall at end
      diastole. In contrast, the distance from the RV free wall to the lateral LV free
      wall was relatively unchanged (2.7 mm). The distance between the LV lateral free
      wall and septum increased more than the distance between the anterior and
      posterior LV walls (22 vs. 15%; P = 0.04). During systole, the displacement of
      the septum into the LV increased significantly (7.3 vs. 2.9 mm; P < 0.01).
      Consistent with the end-diastolic dimension changes, LV endocardial
      circumferential curvature was decreased at end diastole to a greater extent in
      the anterior and posterior walls than in the septal and lateral walls (P < 0.01).
      Thus chronic MR produced an asymmetric LV dilatation with regional variation in
      geometry. The septum increased its contribution to the LVSV at the expense of
      RVEDV. RVSV was maintained, possibly by ventricular interaction.

PMID- 8997333
TI  - Validation of transit-time ultrasound flow probes to directly measure portal
      blood flow in conscious rats.
AB  - Direct measurement of portal venous blood flow is technically difficult, yet
      crucial for accurate assessment of liver hemodynamic and metabolic functions. The
      aim of this investigation was to assess the feasibility of implanting transit
      time ultra-sound (TTUS) perivascular flow probes on the portal vein of the rat
      and to validate this technique as a means of directly measuring portal blood flow
      in conscious rats. A TTUS flow probe was implanted on the portal veins of 10
      rats. One week later, portal flow was measured under basal conditions in these
      rats by TTUS probes and after pharmacological manipulation of portal flow by
      intravenous injections of Glypressin or infusions of adenosine while the rats
      were conscious. Portal flow was simultaneously measured in the same rats using
      radioactive microspheres. Basal systemic hemodynamics, regional blood flows to
      splanchnic organs, and portal blood pressure were not significantly modified by
      the presence of the probe on the portal vein compared with a control group of
      rats not instrumented with flow probes. Basal portal flows measured by the TTUS
      and microsphere techniques were not different (20.6 +/- 2.6 and 17.6 +/- 1.3
      ml/min). After Glypressin, portal flows measured by the TTUS and microsphere
      techniques were 12.3 +/- 2.9 and 9.3 +/- 1.9 ml/min and, in response to
      adenosine, increased to 27.2 +/- 3.4 and 31.3 +/- 4.1 ml/min. There was no
      significant difference between the TTUS and microsphere flows. Both the
      relationship between absolute flows and the relationship between changes in flows
      measured by the two techniques were linear with slopes approaching 1.0. Thus TTUS
      flow probes can be used to directly measure portal flow from the portal vein in
      conscious rats. This methodology is as effective as the standard technique of
      radioactive microspheres. More importantly, the TTUS technique allows for
      continuous direct measurement of portal flow and eliminates the hazards and
      sources of error associated with the radioactive microsphere technique.

PMID- 8997334
TI  - A disrupter of actin microfilaments impairs sulfonylurea-inhibitory gating of
      cardiac KATP channels.
AB  - The efficacy with which sulfonylurea drugs inhibit cardiac ATP-sensitive K+
      (KATP) channels is reduced during metabolic compromise and cellular contracture.
      Disruption of the actin microfilament network, which occurs under similar
      conditions, reduces the sensitivity of the channel toward intracellular ATP. To
      investigate whether a disrupter of actin microfilaments could also affect the
      responsiveness of the KATP channel to sulfonylurea drugs, single-channel currents
      were measured in the inside-out configuration of excised patches from guinea pig
      ventricular myocytes. Treatment of the internal side of patches with
      deoxyribonuclease (DNase) I (100 micrograms/ml), which forms complexes with G
      actin and prevents actin filament formation, antagonized sulfonylurea-induced
      inhibition of KATP channels that was coupled with a loss of sensitivity to ATP.
      The apparent dissociation constant and Hill coefficient for the inhibitory effect
      of glyburide, a prototype sulfonylurea, on KATP-channel opening were,
      respectively, 0.13 microM and 0.95 before and 2.7 microM and 0.98 after DNase
      treatment. DNase did not alter intraburst kinetic properties of the channel. When
      DNase was denatured or coincubated with purified actin (200 micrograms/ml), it no
      longer decreased glyburide-induced channel inhibition. This suggests that
      sulfonylurea-inhibitory gating of cardiac KATP channels may also be regulated
      through a mechanism involving subsarcolemmal actin microfilament networks.

PMID- 8997335
TI  - ATP: the red blood cell link to NO and local control of the pulmonary
      circulation.
AB  - Recently, we reported that rabbit red blood cells (RBCs) were required for the
      expression of nitric oxide (NO) activity on pulmonary vascular resistance (PVR)
      in rabbit lungs. Here, we investigate the hypothesis that RBCs participate in the
      regulation of PVR via release of ATP in response to mechanical deformation that,
      in turn, evokes vascular NO synthesis. We found that rabbit and human RBCs, but
      not dog RBCs, release ATP in response to mechanical deformation. To determine the
      contribution of this ATP to NO synthesis and PVR, we compared the effects of
      human and dog RBCs on pressure-flow relationships in isolated rabbit lungs. In
      the presence of human RBCs, NG-nitro-L-arginine methyl ester (100 microM)
      produced a shift in the pressure-flow relationship consistent with a reduction in
      vascular caliber. NG-nitro-L-arginine methyl ester had no effect in lungs
      perfused with dog RBCs. These results suggest a unique mechanism for the control
      of PVR in rabbits and humans whereby release of ATP by RBCs in response to
      mechanical deformation leads to stimulation of NO synthesis that, in turn,
      modulates the PVR.

PMID- 8997336
TI  - KATP channels mediate late preconditioning against infarction produced by
      monophosphoryl lipid A.
AB  - The cardioprotective effect of myocardial preconditioning (PC) to reduce infarct
      size has been shown to last approximately 90 min (early PC), and then a second
      window of protection (SWOP or late PC) appears 24 h later. Although much work has
      been done to characterize early PC, little has been done to investigate potential
      mediators of SWOP. To that end, we have used monophosphoryl lipid A (MLA), a
      nontoxic endotoxin derivative, to produce SWOP and have examined the role of ATP
      sensitive potassium (KATP) channels in mediating its cardioprotection. Adult
      mongrel dogs were given MLA (3, 10, or 35 micrograms/kg i.v.) 24 h before a 60
      min left anterior descending coronary artery occlusion and 3 h of reperfusion.
      After reperfusion, the hearts were stained for myocardial infarction with
      triphenyltetrazolium. MLA produced a dose-dependent reduction in infarct size
      that was associated with an enhanced shortening of the monophasic action
      potential duration during early ischemia. To further examine the role of KATP
      channels, animals were treated with MLA (35 micrograms/kg) and 24 h later were
      administered either glibenclamide (0.3 mg/kg i.v.) or 5-hydroxydecanoate (7.5
      mg/kg intracoronary over 20 min), two structurally distinct KATP-channel
      antagonists. Both glibenclamide and 5-hydroxydecanoate abolished the
      cardioprotection produced by MLA. These results demonstrate that the
      cardioprotective effect of late PC produced by MLA is dependent on functional
      KATP channels and is the first study to suggest that late PC may be the result of
      an increased KATP current during ischemia.

PMID- 8997337
TI  - Blood flow response to treadmill running in the rat spinotrapezius muscle.
AB  - The rat spinotrapezius muscle has been utilized to investigate the
      microcirculatory consequences of exercise training. It was the purpose of this
      investigation to determine whether, and to what extent, this muscle is recruited
      during treadmill exercise. Radioactive 15-micron microspheres were used to
      measure blood flow to the spinotrapezius and hind limb musculature as well as to
      the abdominal organs of female Wistar rats. Blood flows were measured at rest and
      during two levels of treadmill-running exercise (i.e., 0% grade, 15 m/min and 10%
      grade, 24 m/min). As expected, exercise increased blood flow to the soleus,
      plantaris, red gastrocnemius, mixed gastrocnemius, and white gastrocnemius
      muscles, whereas blood flow to the stomach, intestines, pancreas, spleen, and
      kidneys was decreased (P < 0.05). However, contrary to our expectation, blood
      flow to the spinotrapezius muscle decreased from 61 +/- 6 ml.100 g-1.min-1 at
      rest to 39 +/- 2 ml.100 g-1.min-1 at 0% grade, 15 m/min and 46 +/- 4 ml.100 g
      1.min-1 at 10% grade, 24 m/min (P < 0.05). These findings support the premise
      that treadmill running does not recruit the spinotrapezius muscle and suggest
      that previous training-induced arteriolar adaptations produced in this muscle may
      result from mechanisms unrelated to augmented exercise blood flow or muscle
      metabolism.

PMID- 8997338
TI  - VEGF induces NO-dependent hyperpermeability in coronary venules.
AB  - The purpose of this study was to investigate the direct effect of vascular
      endothelial growth factor (VEGF) on microvascular permeability and its signaling
      mechanisms. The apparent permeability coefficient to albumin was measured in
      isolated coronary venules. Topical application of VEGF dose-dependently and
      transiently increased albumin permeability by two- to threefold. Inhibition of
      nitric oxide (NO) synthesis with NG-monomethyl-L-arginine abolished VEGF-induced
      venular hyperpermeability. Furthermore, because NO exerts vasoactive effects
      through stimulation of guanylate cyclase (GC) and the subsequent production of
      guanosine 3',5'-cyclic monophosphate (cGMP), we examined the role of GC and cGMP
      dependent protein kinase (PKG) in the mediation of VEGF's action. The
      permeability response to VEGF was measured in the presence of the selective GC
      inhibitor 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one and the specific PKG
      inhibitor KT-5823. Both inhibitors reduced basal permeability and prevented the
      hyperpermeability response to VEGF. Therefore, we suggest that VEGF modulates
      microvascular permeability via a signaling cascade involving NO synthesis, GC
      stimulation, and PKG activation.

PMID- 8997339
TI  - Velocity differences between L- and P-selectin-dependent neutrophil rolling in
      venules of mouse cremaster muscle in vivo.
AB  - After surgical trauma, leukocyte rolling is initially normal in L-selectin
      deficient mice and reduced at later times, whereas leukocyte rolling is initially
      absent in P-selectin-deficient mice but induced later. Here, we examined the
      possibility that P- and L-selectin support rolling at different characteristic
      velocities using intravital microscopy of venules of the exteriorized cremaster
      muscle venules of wild type (WT) and P- and L-selectin-deficient mice. At > 50
      min after exteriorization, rolling in P-selectin-deficient mice occurred at
      significantly higher velocities (129 +/- 89 microns/s) than in WT mice (49 +/- 23
      microns/s). Rolling velocity distribution in L-selectin-deficient mice was
      similar to WT mice immediately after exteriorization. Histological examination of
      Giemsa-stained whole-mount preparations in cremaster muscle venules revealed that
      the majority of rolling cells (approximately 90% in all genotypes) were
      granulocytes. We conclude that P-selectin mediates leukocyte rolling at
      velocities < 50 microns/s, whereas L-selectin sustains more rapid rolling. Under
      physiological conditions, P- and L-selectin synergize to support rolling at
      velocities between 20 and 70 microns/s as seen in WT mice.

PMID- 8997340
TI  - Regulation of microvascular filtration in the myocardium by interstitial fluid
      pressure.
AB  - We hypothesized that myocardial microvascular filtration rate (Jv) could be
      manipulated by varying end-diastolic myocardial interstitial hydrostatic (P(int))
      pressure. Dogs under general anesthesia were instrumented with intramyocardial
      capsules to measure P(int) and with prenodal myocardial lymphatic trunk cannulas
      and superior vena caval balloon-tipped catheters to manipulate myocardial lymph
      flow. Because, for a given surface area, the lymph-to-plasma protein
      concentration ration (CL/CP) varies inversely with JV, CL/CP was utilized as an
      index of changes in JV. When lymphatic outflow pressure (P0) was elevated to
      abolish lymph flow and force myocardial interstitial fluid volume to expand,
      P(int) rose significantly from 15.0 +/- 0.8 to 27.6 +/- 1.0 mmHg and CL/CP
      increased significantly from 0.75 +/- 0.04 to 0.85 +/- 0.04, indicating a
      decrease in JV. When P0 was lowered and lymph flow resumed, P(int) and CL/CP
      decreased significantly to 15.3 +/- 0.9 mmHg and 0.75 +/- 0.04, respectively,
      indicating an increase in JV. We conclude that myocardial microvascular
      filtration rate may be modulated by changes in P(int) resulting from alterations
      in myocardial interstitial fluid volume secondary to variations in lymph flow
      from the heart.

PMID- 8997342
TI  - Phosphaturic effect of L-NMMA in the presence of parathyroid hormone.
AB  - The objective of this study was to examine the effect of NG-monomethyl-L-arginine
      (L-NMMA) on phosphate excretion in the presence and absence of parathyroid
      hormone (PTH). Renal clearances were obtained before and during infusion of L
      NMMA (15 mg/kg bolus and 500 micrograms.kg-1.min-1 infusion) in Sprague-Dawley
      rats with intact parathyroid glands (n = 6), in thyroparathyroidectomized (TPTX)
      rats receiving a constant infusion of PTH-(1-34) (0.01-0.03 U.kg-1.min-1) (n =
      11) throughout the experiment, or in TPTX rats, that received an acute infusion
      of PTH-(1-34) (33 U/kg bolus and 1 U.kg-1.min-1 infusion) after L-NMMA infusion
      alone (n = 7). In rats with intact parathyroid glands, L-NMMA increased the
      fractional excretions of phosphate (FEPi) and sodium (FENa) and mean arterial
      pressure (MAP) (delta 8.6 +/- 1.5%, delta 0.62 +/- 0.1%, and delta 26.7 +/- 4.9
      mmHg, respectively; P < 0.05). In TPTX rats receiving a constant infusion of PTH,
      L-NMMA again increased FEPi, FENa, and MAP (delta 9.5 +/- 3.6%, delta 1.1 +/-
      0.4%, and delta 28.4 +/- 4.5 mmHg, respectively; P < 0.05). However, in TPTX
      rats, L-NMMA alone did not increase FEPi (delta 0.9 +/- 0.3%), whereas the
      subsequent infusion of PTH with L-NMMA increased FEPi (delta 15.6 +/- 3.1%; P <
      0.05). In an additional group of intact and TPTX rats, the fractional excretion
      of lithium (FELi) was measured as an index of proximal reabsorption. L-NMMA
      increased FELi in intact rats (delta 13.2 +/- 2.6%; P < 0.05), but not in TPTX
      rats (delta 4.2 +/- 3.3%). In conclusion, L-NMMA increases phosphate excretion in
      association with increases in MAP and FENa, and this phosphaturic effect is
      dependent on the presence of PTH.

PMID- 8997341
TI  - Forebrain angiotensin type 1 receptors and parabrachial serotonin in the control
      of NaCl and water intake.
AB  - This study investigated the roles of serotonin (5-HT) receptors in the lateral
      parabrachial nucleus (LPBN) and brain angiotensin type 1 (AT1) receptors in the
      intake of 0.3 M NaCl and water induced by angiotensin II (ANG II). Rats were
      implanted with stainless steel cannulas for injections into the subfornical organ
      (SFO) and into the LPBN. Bilateral LPBN pretreatment with the nonselective
      serotonergic 5-HT1/5-HT2 receptor antagonist methysergide (4 micrograms/200 nl)
      markedly enhanced 0.3 M NaCl intake induced by injections of ANG II (20 ng/200
      nl) into the SFO. Pretreatment of the SFO with the AT1 receptor antagonist
      losartan (1 microgram/200 nl) blocked the intake of 0.3 M NaCl induced by ANG II
      in combination with LPBN methysergide injections. These results suggest that
      serotonergic mechanisms associated with the LPBN inhibit the expression of salt
      appetite induced by ANG II injections into the SFO. In addition, the results
      indicate that the enhanced NaCl intake generated by central administration of ANG
      II in the presence of LPBN 5-HT blockade is mediated by brain AT1 receptors.

PMID- 8997343
TI  - Reorganization of the innervation of the vas deferens after sympathetic
      decentralization.
AB  - Reorganization of autonomic efferent pathways to the rat vas deferens was noted
      after chronic (30 days) sympathetic decentralization produced by hypogastric
      nerve (HGN) transection. In normal rats, electrical stimulation of the HGN
      elicited an increase in vasal pressure (VP) bilaterally, whereas pelvic nerve
      (PN) stimulation did not alter VP. However, after unilateral HGN transection,
      stimulation of the PN on the transected side but not on the normal side increased
      VP. The decentralized vas exhibited larger VP responses to stimulation of the
      contralateral HGN in comparison with the normal vas. After bilateral HGN
      transection, PN-induced VP responses were elicited at lower stimulus intensities
      than in rats with unilateral transections. PN-induced VP responses were blocked
      by hexamethonium and prazosin but were not altered by atropine. Distension of the
      vas lumen occurred after decentralization. PN-induced VP responses were not
      detectable in extremely distended vas. These data indicate that, after
      degeneration of sympathetic preganglionic axons, decentralized adrenergic
      ganglion cells are reinnervated by parasympathetic or sympathetic preganglionic
      pathways and that the reinnervation influences vasal function.

PMID- 8997344
TI  - Functional response to graded increases in renal nerve activity during hypoxia in
      conscious rabbits.
AB  - Changes in renal sympathetic nerve activity (SNA) are postulated to influence
      renal function in selective ways, such that different levels of activation
      produce particular renal responses, initially in renin release, then sodium
      excretion, with changes in renal hemodynamics occurring only with much greater
      stimulus intensities. The aim of this study was to determine the renal
      hemodynamic and excretory responses to graded physiological increases in renal
      SNA induced by breathing different hypoxic gas mixtures. Experiments were
      performed in seven conscious rabbits subjected to four gas mixtures (14% O2, 10%
      O2, 10% O2 + 3% CO2, and 10% O2 + 5% CO2) and instrumented for recording of renal
      nerve activity. After a 30-min control period, rabbits were subjected to one of
      the four gas mixtures for 30 min, and then room air was resumed for a further 30
      min. The four gas mixtures increased renal SNA by 14, 38, 49, and 165%
      respectively, but arterial pressure (thus renal perfusion pressure) was not
      altered by any of the gas mixtures. The greatest level of sympathetic activation
      produced significant falls in glomerular filtration rate (GFR), renal blood flow,
      sodium and fluid excretion, and significant increases in plasma renin activity.
      These returned to levels not significantly different from control conditions in
      the 30-min period after the gas mixture. When the changes to the various gas
      mixtures were analyzed within each rabbit, a significant linear relationship was
      found with all variables to the increase in SNA. Renal denervation in a separate
      group of seven rabbits completely abolished all of the above responses to the
      different gas mixtures. Thus graded activation of renal nerves induced by changes
      in inspired gas mixtures resulted in graded decreases in renal blood flow, GFR,
      and sodium excretion and graded increases in renin activity, with the changes
      occurring across a similar range of nerve activities; there was no evidence for a
      selective change in any renal variable.

PMID- 8997345
TI  - Subthreshold stimulation of a serotonin 5-HT3 reflex attenuates cardiovascular
      reflexes.
AB  - Volume-sensitive and chemosensitive cardiopulmonary reflexes modulate volume
      homeostasis via renal sympathetic nerve activity (RSNA). Blunting of volume
      sensitive cardiopulmonary reflexes is associated with volume retention, e.g., in
      hypertension, whereas the role of chemosensitive cardiopulmonary reflexes is
      largely unknown. To elucidate the possible role of chemosensitive cardiopulmonary
      reflexes in control of volume homeostasis, we investigated whether subthreshold
      stimulation of 5-HT3 receptors modulates the control of RSNA by volume-sensitive
      cardiopulmonary reflexes or the arterial baroreceptor reflex in rats. Phenyl
      biguanide (PBG) was infused intravenously to stimulate 5-HT3 receptors. Higher
      doses of PBG lowered RSNA, but a dose of 6 micrograms/min, given as a background
      infusion throughout the experiment, did not change arterial pressure, heart rate
      (HR), or RSNA. Ten minutes after beginning the 6 micrograms/min PBG infusion, a
      15-min volume expansion (0.9% saline, 5 or 10% body weight) was started to
      stimulate volume-sensitive cardiopulmonary reflexes. In separate experiments, 5
      min ramp infusions of methoxamine and nitroglycerin to stimulate the arterial
      baroreceptor reflex (evaluated by a 4-parameter logistic regression) were
      performed 15 min after beginning the PBG background infusion (6 micrograms/min).
      During PBG infusion, the RSNA responses to volume expansions were significantly
      impaired (5% body weight: PBG -6 +/- 6%, n = 7 vs. control -39 +/- 9%, n = 6, P <
      0.001; 10% body weight: PBG -33 +/- 6%, n = 8 vs. control -52 +/- 5%, n = 7, P <
      0.05). The 5-HT3 receptor antagonist odansetron (GR-38032F) abolished these
      effects of PBG. The maximum HR gain of the arterial baroreceptor reflex was
      impaired but the arterial baroreceptor control of RSNA was unaffected by PBG
      background infusion. We conclude that 5-HT3-serotonergic cardiopulmonary
      chemoreceptors blunt the RSNA decrease to volume loading. This mechanism may
      facilitate volume retention when cardiac serotonin is increased.

PMID- 8997346
TI  - Angiotensin II and the maturation of renal cortical Na+/H+ exchanger activity
      during fetal life in sheep.
AB  - The postnatal rise in renal Na+ reabsorption is associated with an increase in
      proximal tubule apical membrane Na+/H+ exchanger (NHE) activity in sheep.
      Inasmuch as circulating angiotensin II (ANG II) levels increase immediately after
      birth and ANG II is known to upregulate NHE activity in the adult proximal
      tubule, we postulated that ANG II plays a role in mediating maturational changes
      in NHE activity. We therefore studied the effects of ANG II infusion (10
      micrograms/h) for 24 h on renal cortical NHE activity in chronically
      instrumented, twin ovine fetuses (129 +/- 2 days gestation, term is 145 days, n =
      10 pairs); one twin of each pair served as a control. After 24 h, the fetuses
      were killed and brush-border membrane vesicles (BBMV) were prepared from the
      renal cortices. Postinfusion plasma ANG II levels were significantly higher and
      plasma renin activities were significantly lower in treated fetuses compared with
      controls. Kinetic analysis revealed an increase in NHE activity after ANG II
      treatment; however, the difference was not statistically significant: maximal
      velocity (in nmol.s-1.mg protein-1) control 1.65 +/- 0.50, treated 2.31 +/- 0.66
      (P = 0.11, n = 9 pairs); Michaelis constant control 8.29 +/- 1.17 mM, treated
      9.84 +/- 1.26 mM (P = 0.11). Northern blots of total RNA from the cortices of
      these animals were hybridized to a D-[32P]UTP-labeled antisense RNA probe
      prepared from a 1.3-kb rat NHE3 cDNA fragment. There were no differences between
      the groups in NHE3 mRNA levels (32P counts were control 413 +/- 54, treated 340
      +/- 46). ANG II does not appear to play an important role in the regulation of
      NHE activity in the proximal tubule of the near-term sheep fetus.

PMID- 8997347
TI  - Aging affects development and persistence of feeding-associated circadian rhythm
      in rat plasma corticosterone.
AB  - Effects of aging on development and persistence of feeding-associated circadian
      rhythm were examined with respect to the prefeeding plasma corticosterone peak
      under restricted feeding. Old (20 mo), middle-aged (12 mo), and young (2.5 mo)
      male rats were subjected to a restricted feeding schedule for 21 days in which
      free access to food was limited to 2 h/day in the light phase. Prefeeding
      corticosterone peak was detected 1 wk after the start of the schedule in the
      young and 3 wk after in the old and middle-aged rats. After the restricted
      feeding, a feeding/ fasting cycle composed of 7 days of ad libitum feeding and 3
      days of fasting was imposed four times. The persistence of feeding-associated
      rhythm was evaluated by examining the reappearance of the corticosterone peak at
      the previous meal time during each fasting period of the feeding/fasting cycle.
      The corticosterone peak was not detected in the old and middle-aged rats even at
      the first cycle, but it was still distinct at the third cycle in the young rats.
      In conclusion, aging impaired the development and persistence of feeding
      associated circadian rhythm in rats.

PMID- 8997348
TI  - Role of cholecystokinin in the anorexia produced by duodenal delivery of glucose
      in rats.
AB  - We used the type A cholecystokinin receptor (CCK-AR) antagonist devazepide to
      assess the importance of CCK in mediating the anorexia produced by 2-h duodenal
      infusions of glucose (9.2, 11.0, and 18.3 mmol.kg-1.h-1) and the glucose dimer
      maltose (4.5, 6.7, and 8.5 mmol.kg-1.h-1) at the start of the dark period in
      nonfasted rats with free access to food. Glucose and maltose appeared to inhibit
      2- to 3-h food intakes dose dependently from 19 to 91%. The highest doses of
      glucose and maltose administered suppressed feeding similarly by increasing first
      meal latency and decreasing meal frequency; lower doses produced less reliable
      effects on meal patterns. Devazepide appeared to completely reverse the
      cumulative intake responses and some of the meal pattern responses to the 9.2
      mmol.kg-1.h-1 dose of glucose and to partially attenuate responses to the two
      higher glucose doses and to the minimal effective dose of maltose (6.7 mmol.kg
      1.h-1). The magnitudes of these devazepide effects were not statistically
      different from those produced by devazepide when vehicle was infused duodenally.
      These results suggest that CCK may play a significant necessary role in mediating
      the satiety response to duodenal delivery of small but not large loads of
      glucose.

PMID- 8997349
TI  - Ventricular remodeling during development and recovery from modified tachycardia
      induced cardiomyopathy model.
AB  - This study was designed to characterize left ventricular (LV) function and mass
      in a modified cardiomyopathy model in the dog in which right ventricular pacing
      rates are gradually increased throughout 38 days. On the last day of the pacing
      protocol, ejection fraction was reduced (25 +/- 3 vs. 60 +/- 1%) and LV end
      diastolic diameter index (a ratio of LV end-diastolic diameter to body weight,
      2.09 +/- 0.02 vs. 1.79 +/- 0.08 mm/kg) and LV mass index (a ratio of LV mass to
      body weight, 5.2 +/- 0.3 vs. 4.3 +/- 0.2 g/kg) were greater than in the normal
      dogs (P < 0.05, respectively). Cardiac filling pressures increased, and LV
      diastolic function and coronary blood flow were impaired. After 4 wk of recovery
      from the progressive pacing protocol, LV end-diastolic diameter index (2.12 +/-
      0.06 mm/kg) and LV mass index (5.6 +/- 0.2 g/kg) remained increased. Ejection
      fraction was improved (38 +/- 4%) but still depressed. LV diastolic function,
      coronary blood flow, and cardiac filling pressures returned to levels seen in the
      normal dogs. This modified cardiomyopathy model associated with LV hypertrophy
      complements the conventional tachycardia-induced cardiomyopathy model without LV
      hypertrophy.

PMID- 8997350
TI  - Water transport in collecting ducts of Japanese quail.
AB  - Previously, we reported that the countercurrent urine concentration mechanism in
      birds appears to operate by recycling of a single solute (NaCl), in which the
      thick ascending limb of looped nephrons provides an energy source. To determine
      the importance of the medullary collecting duct (MCD) in the countercurrent
      multiplier system, we examined in isolated and perfused MCDs from Japanese quail,
      Coturnix coturnix, the osmotic and/or diffusional water permeability and whether
      arginine vasotocin (AVT) regulates water permeability. We noted that dark cells
      that possess electron-dense cytoplasm and numerous mitochondria and light mucus
      secreting cells exist in the cortical collecting duct (CD), whereas only mucus
      secreting cells are present in the MCDs. The volume flux (Jv) in the MCDs from
      intact birds and that from the water-deprived birds were nearly zero; after
      exposure to a hyperosmotic bath and AVT (2 x 10(-5) M), the Jv was significantly
      higher in water-deprived birds. The diffusional water permeability (Pdw) was
      moderately high in MCDs bathed in an isosmotic bath in which the Pdw was
      increased slightly by AVT (10(-5) M, bath) and more markedly (10(-5) M) by
      forskolin (Fsk), whereas 1,9-dideoxy Fsk (an inactive analogue) showed no effect.
      Furthermore, the basal adenosine 3',5'-cyclic monophosphate (cAMP) levels were
      higher in the medulla than in the cortex and were stimulated only slightly by AVT
      (10(-5) M) and markedly by Fsk (10(-4) M) in both the cortex and medulla. These
      results in the C. coturnix CD indicate the following. 1) Two types of cells are
      present; whereas dark cells resemble mammalian intercalated cells
      morphologically, it is not certain whether mucus-secreting cells are equivalent
      to principal cells. 2) AVT increases Pdw via a cAMP mechanism; the relatively
      high basal Pdw and minor effect of AVT on Jv and Pdw suggest, however, that
      diffusional water movement across the MCD may occur without significant direct
      control by AVT.

PMID- 8997351
TI  - Chloride and taurine effluxes occur by different pathways in skate erythrocytes.
AB  - The aim of this study was to determine whether volume-activated taurine and Cl-
      effluxes occur via the same system in skate (Raja erinacea) red blood cells
      (RBC). The effluxes were measured in isotonic and hypotonic elasmobranch Ringer
      solutions, in which NaCl was replaced by mannitol and the remaining exchangeable
      anions with gluconate. Methazolamide (0.1 mM) was added to minimize HCO3-
      formation. RBC Cl- content fell approximately 50%/h in both isotonic and
      hypotonic media, with no detectable K- loss in either medium. The observed Cl-
      loss was accompanied by an increase in pH. Both the Cl- loss and pH rise were
      inhibited by 4,4'- diisothiocyanostilbene-2,2'-disulfonic acid (0.1 mM),
      suggesting that Cl- efflux was due to H(+)-Cl- cotransport. 36Cl- effluxes in
      isotonic and hypotonic media were (means +/- SE, n = 11) 2.8 +/- 0.6 and 3.5 +/-
      0.9 mumol.g dry wt RBC-1.min-1, respectively, whereas [3H]taurine effluxes in the
      same media were 0.045 +/- 0.02 and 2.1 +/- 0.05 mumol.g dry wt RBC-1.min-1,
      respectively (n = 6). These results indicate that taurine and Cl- effluxes occur
      via different pathways in skate RBC. In addition, the swelling-activated Cl-
      channel reported in epithelial cells does not appear to be present in skate RBC.
      This conclusion was confirmed by Western blots with an antibody to swelling
      activated Cl- channels. Taurine and Cl- fluxes are apparently under different
      pathway influences in these RBC: taurine diffuses via a channel, whereas Cl- is
      transported by cotransporters.

PMID- 8997352
TI  - Allometry of mitochondrial proton leak: influence of membrane surface area and
      fatty acid composition.
AB  - We investigated why liver mitochondria from small mammals are leakier to protons
      than those from larger mammals. Sixty-nine percent (+/-23%) of the proton leak
      differences appeared to relate to membrane area (less inner membrane surface area
      in larger animals); any residual differences must reflect differences in membrane
      properties. There were differences in phospholipid fatty acid composition;
      unsaturation index, monounsaturates, palmitate (16:0), stearate (18:0),
      docosahexaenoate [22:6(n-3)], and the 22:6(n-3)/22:5(n-3) ratio all correlated
      with body mass. Proton flux per square centimeter did not correlate significantly
      with body mass or, in general, with phospholipid fatty acid composition,
      suggesting little role for fatty acid composition in determining proton leak in
      mammals of different body mass. However, unsaturation index and n-3
      polyunsaturated fatty acid content correlated significantly with proton leak per
      milligram phospholipid when literature data from reptiles and rats in different
      thyroid states were included, giving some support to suggestions of a general
      role for phospholipid fatty acid composition in determining mitochondrial proton
      leak.

PMID- 8997353
TI  - Stimulation of Na(+)-K(+)-2Cl- cotransport in rat medullary thick ascending limb
      by dopamine.
AB  - Dopamine receptors are present in the medullary thick ascending limb (mTAL) of
      Henle, but their effect on ion transport in this nephron segment has not been
      tested. Therefore, we studied the short-term effects of dopamine on Na(+)-K(+)
      2Cl- cotransport (assessed by 100 microM bumetanide-sensitive 86Rb uptake) in rat
      mTAL tubular suspensions. Dopamine (1 microM) stimulated bumetanide-sensitive
      86Rb uptake (72.1 +/- 10.6% vs. control, n = 5) by increasing total 86Rb uptake
      and by decreasing bumetanide-insensitive 86Rb uptake; this effect was
      concentration dependent. The dopamine-induced stimulation of Na(+)-K(+)-2Cl-
      cotransport activity was mimicked by calyculin A, a protein phosphatase (PP)
      inhibitor, and Sp isomer of adenosine 3',5'-cyclic monophosphothioate (Sp
      cAMP[S]), a protein kinase A (PKA) agonist, and blocked by Rp isomer of 8-(4
      chlorophenylthio)-cAMP[S] (Rp-8-CPT-cAMP[S]), a PKA inhibitor (n = 5). Dopamine
      did not increase the stimulatory effect of the PP inhibitor. However, the
      stimulatory effect of the PP inhibitor and PKA agonist was additive and
      approached the stimulatory effect of dopamine. The stimulatory effects of
      dopamine, PP inhibitor, and PKA agonist persisted even when intracellular sodium
      was clamped by 5 microM monensin. When K+ channels were blocked by 1 mM BaCl2,
      the effects of dopamine and calyculin A on the cotransport were no longer
      apparent, although the stimulatory effect of the PKA agonist was attenuated. We
      conclude that dopamine stimulates Na(+)-K(+)-2Cl- cotransport activity. This
      action is mediated mainly by PKA-dependent phosphorylation/dephosphorylation
      processes and modulated by dopamine actions on K+ channels.

PMID- 8997354
TI  - Glutamate microinjections in cerebellar cortex reproduce cerebrovascular effects
      of parallel fiber stimulation.
AB  - Electrical stimulation of cerebellar parallel fibers releases glutamate and
      increases local blood flow (BFcrb), an effect in part mediated by glutamate
      induced nitric oxide (NO) production. We studied whether local microinjection of
      glutamate into the cerebellar cortex would produce increases in BFcrb comparable
      to those elicited by parallel fiber stimulation. In halothane-anesthetized rats
      equipped with a cranial window, glutamate was microinjected into the cerebellar
      molecular layer, and BFcrb was monitored by laser-Doppler flowmetry. Glutamate
      microinjections increased BFcrb dose dependently (2-200 pmol in 200 nl) (n = 9)
      and by 55 +/- 6% at 200 pmol (mean +/- SE). The magnitude and temporal profile of
      the increases in BFcrb compared favorably with the increase in flow produced by
      parallel fiber stimulation. The glutamate-induced BFcrb increase was attenuated
      by superfusion with the Na2+ channel blocker tetrodotoxin (10 microM; -50 +/-
      10%; n = 5; P < 0.05; t-test) or by blocking synaptic activity by treatment of
      the cerebellar cortex with Ringer containing 20 mM Mg2+ and 0 mM Ca2+ (-80 +/-
      4%; n = 6; P < 0.05). The glutamate-receptor antagonist kynurenate (10 mM)
      attenuated the increase in BFcrb by 59 +/- 6% (P < 0.05; n = 5). The relatively
      selective inhibitor of neuronal NO synthase 7-nitroindazole (100 mg/kg ip)
      reduced the flow response evoked by microinjection of glutamate (-46 +/- 7%; n =
      5; P < 0.05) but not acetylcholine (10 microM; P > 0.05; n = 6). We conclude that
      glutamate microinjections increase local BFcrb via activation of glutamate
      receptors. The glutamate-induced vasodilation is mediated, in part, by neurally
      derived NO. The striking similarities between the vascular responses evoked by
      parallel fiber stimulation and that produced by microinjection of glutamate
      support the hypothesis that the increase in BFcrb produced by parallel fiber
      stimulation is mediated by glutamate release and activation of glutamate
      receptors. The data also strengthen the hypothesis that glutamate and NO are
      important mediators in the mechanisms linking synaptic activity to BFcrb in
      cerebellar cortex.

PMID- 8997355
TI  - Na(+)-D-glucose cotransport by intestinal BBMVs of the Antarctic fish Trematomus
      bernacchii.
AB  - Intestinal nutrient absorption in fish adapted to low temperature was
      investigated by isolating, with a Mg(2+)-precipitation procedure, brush-border
      membrane vesicles (BBMVs) from intestines of the Antarctic teleost Trematomus
      bernacchii. In particular, D-glucose transport was analyzed by measuring both 1)
      fluorescence changes of the electrical potential-sensitive dye 3,3'
      diethylthiadicarbocyanine iodide [DiS-C2(5)] and 2) intravesicular uptake of D
      [14C]glucose. Results demonstrated that transport of D-glucose across intestinal
      BBMs of the Antarctic fish is stimulated by the presence of a transmembrane Na+
      gradient (out > in) and was specifically inhibited by phloridzin. Furthermore,
      Na(+)-dependent D-glucose uptake was strongly enhanced by the presence of an
      electrical potential (inside-negative) across the membrane. There was a marked
      difference in temperature dependence of Na(+)-sugar cotransport between the
      Antarctic fish and a temperate fish, such as the European yellow eel., Na(+)
      dependent D-glucose uptake in T. bernacchii intestinal BBMV reached its maximal
      rate at -2-0 degree C (close to fish living temperature) and was exponentially
      inactivated by incubation at higher temperatures. Kinetic analysis of D-glucose
      influx indicated the presence of a single Na(+)-dependent carrier process
      (apparent maximal carrier-mediated influx = 0.233 +/- 0.009 nmol.mg protein-1.min
      1; apparent half-saturation constant for carrier-mediated influx = 0.157 +/-
      0.026 mmol/l) and a nonsaturable transfer component (apparent diffusional
      permeability of membrane to the sugar = 0.233 +/- 0.016 microliter.mg protein
      1.min-1). The Na(+)-dependent carrier-mediated mechanism was specific for sugars,
      since it was partially inhibited by the presence in the extravesicular medium of
      other monosaccharides, but not by ascorbic acid or amino acids of different
      types. These data suggest that in the intestine of Antarctic fish luminal D
      glucose transport takes place by a specific Na(+)-dependent electrogenic
      secondary active transport working well at subzero temperatures.

PMID- 8997356
TI  - Peripheral bombesin induces gastric vagal afferent activation in rats.
AB  - Bombesin's influence on gastric vagal afferent discharge (GVAD) was studied in
      urethan-anesthetized rats. Vehicle and peptides were injected intravenously at 30
      min intervals. Cholecystokinin (CCK; 300 pmol) and bombesin (300 pmol) increased
      ongoing multiunit GVAD by 153 +/- 59 and 162 +/- 37%, respectively; similar
      increases were induced by a second injection of bombesin and CCK. The bombesin
      antagonist, ICI-216140, prevented bombesin-induced increase in GVAD, whereas the
      CCK response was not influenced. The CCK-A receptor antagonist devazepide reduced
      the activation of GVAD induced by bombesin from 107 +/- 11 to 63 +/- 6%, while
      abolishing the CCK response. Devazepide given alone or in combination with ICI
      216140 did not modify gastric distension (3 ml)-induced increase in GVAD. Of 22
      single units that were activated by gastric load (4 ml), 17 and 20 units
      responded also to bombesin (620 pmol) and CCK (870 pmol), respectively. Of the
      nine units that did not respond to gastric load, eight had an increase in GVAD
      induced by both bombesin and CCK. There was no specific binding of 125I-labeled
      [Tyr4]bombesin on cervical vagus, either intact or 24 h after ligation. These
      data suggest that intravenous bombesin-induced stimulation of GVAD is indirect
      and initially mediated through specific receptor activation influencing gastric
      smooth muscle and the release of CCK.

PMID- 8997357
TI  - Ontogeny of blood-brain barrier function in ovine fetuses, lambs, and adults.
AB  - The ontogeny of regional blood-brain barrier function was quantified with the
      rate constant for influx (Ki) across the blood-brain barrier with the small
      molecular weight synthetic, inert hydrophilic amino acid alpha-aminoisobutyric
      acid (AIB) in chronically instrumented early (87 days of gestation, 60% of
      gestation) and late (137 days of gestation, 90% of gestation) gestation fetal,
      newborn (3 days of age), older (24 days of age), and adult (3 years of age)
      sheep. The Ki was significantly (P < 0.05) lower in the brain regions of the
      adult sheep and in most brain regions of newborn and older lambs compared with
      fetuses at 60 and 90% of gestation. The Ki exhibited regional brain heterogeneity
      (P < 0.05) in the five groups. The patterns of regional heterogeneity were
      accentuated (P < 0.05) in the younger groups. We conclude that ontogenic
      decreases in blood-brain barrier permeability are observed in ovine fetuses from
      60% of gestation to maturity in the adult.

PMID- 8997358
TI  - Age-related changes in the responsiveness of apolipoprotein A1 to thyroid
      hormone.
AB  - To determine the age-related changes in the effect of thyroid hormone on
      apolipoprotein A1 (ApoA1) gene expression, male Fischer 344 rats at 4 (young) and
      26 (aged) mo of age were studied. Hyperthyroidism was induced with daily
      intraperitoneal injections of 3,5,3'-triiodothyronine (15 micrograms/100 g body
      wt) for 10 days. Hypothyroidism was induced with 0.025% methimazole in drinking
      water for 4 wk. Hyperthyroidism was associated with increased serum ApoA1 levels
      in young rats [7.52 +/- 0.41 vs. 3.67 +/- 0.30 optical density (OD); P < 0.01].
      The increase in aged rats (6.5 +/- 0.87 vs. 5.14 +/- 0.09 OD) did not reach
      statistical significance. Hypothyroidism was not associated with significant
      changes in serum ApoA1 levels in either young or aged rats. Hyperthyroidism was
      associated with a 2.5-fold increase in ApoA1 mRNA in young rats and a 1.7-fold
      increase in aged rats. Hypothyroidism was associated with a 3.6-fold reduction in
      ApoA1 mRNA in young rats, but there was no significant change in aged hypothyroid
      rats. Mobility shift assays indicated that the binding of transacting factors to
      ApoA1 promoter increased in hyperthyroid young rats but not in hyperthyroid aged
      rats. It is concluded that aging in rats is associated with reduced ApoA1
      responsiveness to thyroid hormones. This altered responsiveness could partly be
      the result of changes in the binding activity of nuclear factors to the ApoA1
      promoter.

PMID- 8997359
TI  - Cellular immunity is not compromised by high serum corticosterone concentrations
      in prairie voles.
AB  - Glucocorticoids compromise immune function in glucocorticoid-sensitive species
      (e.g., mice), but these immunosuppressive effects may be reduced in
      glucocorticoid-resistant species. Prairie voles (microtus ochrogaster) have been
      characterized as glucocorticoid-resistant to their high circulating levels of
      corticosterone. Because glucocorticoid-sensitive species display suppressed
      lymphocyte proliferation in response to elevated blood glucocorticoid levels,
      proliferative values were hypothesized to be reduced in house mice (Mus musculus)
      compared with prairie voles. Prairie voles exhibited significantly higher
      splenocyte proliferative responses to the T cell mitogen, Concanavalin A, despite
      having higher basal total and free serum corticosterone levels than mice. Neither
      total nor free serum corticosterone correlated with proliferative responses from
      either species. These data provide further evidence for glucocorticoid resistance
      in prairie voles and suggest that the interactions between the hypothalamic
      pituitary-adrenal axis and the immune system in prairie voles may differ from
      those in mice or other glucocorticoid-sensitive species. Therefore, prairie voles
      may serve as a valuable animal model for the syndrome of glucocorticoid
      resistance in humans and the role of glucocorticoids in conditions characterized
      by a hyperactive immune system.

PMID- 8997361
TI  - Unilateral smoke inhalation in sheep: effect on left lung lymph flow with right
      lung injury.
AB  - We previously reported that smoke inhalation to the right lung will result in
      damage to the air-insufflated left lung. In this study we confirm these findings
      and determine whether this injury is associated with an elevation in lung lymph
      flow and pulmonary microvascular permeability to protein as indexed by changes in
      reflection coefficient. Sheep (n = 12) were surgically prepared by placement of a
      Swan-Ganz catheter and pneumatic occluders on all pulmonary veins and the left
      pulmonary artery. The left lung lymphatic was selectively cannulated as shown
      previously (Y. Kikuchi, H. Nakazawa, and D. Traber. Am. J. Physiol. 269
      (Regulatory Integrative Comp. Physiol. 38): R943-R947, 1995). All afferent
      lymphatics from the right lung were severed, and the right pulmonary ligament was
      sectioned. The caudal end of the lymph node was sectioned to remove systemic
      lymph contamination. The sheep were studied in the unanesthetized state 7 days
      later. To ensure that lymph flow was exclusively from the left lung (QLL), right
      pulmonary microvascular pressure was increased, a procedure that resulted in
      little or no change in QLL, as was previously shown. The sheep were then
      anesthetized, and a Carlens tube was positioned to allow separate ventilation of
      the right and left lung. The right lungs of five sheep and the left lungs of two
      sheep were insufflated with cotton smoke. Insufflation of the left lung with
      cotton smoke produced a fourfold increase in QLL that began 4 h after insult.
      Insufflation of the right lung with smoke led to a doubling of QLL that began 12
      h after insult. Changes in QLL were associated with increased microvascular
      permeability, as indexed by the reflection coefficient. Control sheep (air
      insufflated into both lungs, n = 5) showed no change in QLL. Injury to the right
      lung resulted in damage to the left air-insufflated lung, suggesting a
      hematogenous mediation of the response.

PMID- 8997360
TI  - Three types of postsynaptic glutamatergic receptors are activated in DMNX neurons
      upon stimulation of NTS.
AB  - While it is widely accepted that parasympathetic activity plays a significant
      role in cardiovascular, bronchomotor, and gastrointestinal function, little is
      known about the synaptic control of parasympathetic vagal neurons. In this study,
      we identified the neurotransmitter(s) and postsynaptic responses in dorsal motor
      nucleus of the vagus (DMNX) neurons upon stimulation of the nucleus of the
      solitary tract (NTS). Neurons were visualized in rat brain stem slices, and
      perforated patch-clamp techniques were used to record postsynaptic currents. NTS
      stimulation activated glutamatergic currents in DMNX that were separated into N
      methyl-D-aspartate (NMDA) and non-NMDA components using D-2-amino-5
      phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. The non
      NMDA component was further characterized using cyclothiazide and concanavalin A
      to block desensitization of DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic
      acid (AMPA) and kainate receptors, respectively. Cyclothiazide increased the
      postsynaptic amplitude, whereas concanavalin A augmented duration, suggesting
      kainate, but not AMPA, currents are curtailed by desensitization. High frequency
      stimulations did not alter synaptic efficacy. In conclusion, this study
      demonstrates the existence of a monosynaptic glutamatergic pathway from NTS that
      activates NMDA, kainate, and AMPA postsynaptic receptors in DMNX neurons.

PMID- 8997362
TI  - Impairment of vascular function is associated with an age-related increase of
      lipid peroxidation in rats.
AB  - We tested the hypothesis that an increase in endogenous lipid peroxidation over
      time is associated with an impairment of endothelium-dependent vascular function
      in resistance-sized mesenteric arteries that is due in part to alterations of
      arachidonate metabolism. Susceptibility to red blood cell hemolysis and sera
      levels of malondialdehyde were increased (P < 0.05) from 20 wk (n = 12) to 40 wk
      (n = 12) in female Sprague-Dawley rats. Arteries were studied in a myograph by
      examining the endothelial modification of phenylephrine vasoconstriction and the
      relaxation responses of the mesenteric arteries to methacholine. We observed the
      following. 1) An increase in sensitivity to alpha 1-adrenergic stimulation
      occurred between 20 and 40 wk of age. Cyclooxygenase inhibition decreased the
      sensitivity to phenylephrine only in the arteries from the 40-wk-old rats,
      indicating that a cyclooxygenase-dependent vasoconstrictor was modifying the
      phenylephrine response. 2) Nitric oxide synthase inhibition caused a greater
      increase in phenylephrine sensitivity in the arteries from the 20-wk-old rats
      than those from the 40-wk-old rats, indicating that nitric oxide modification of
      phenylephrine sensitivity decreased with age. 3) Endothelium-independent
      relaxations were not affected between 20 and 40 wk of age. 4) At 40 wk, the
      sensitivity to the methacholine-mediated relaxation response decreased without
      impairing the maximal relaxation response. This reduced sensitivity was removed
      with cyclooxygenase inhibition or thromboxane A2/prostaglandin H2 (PGH2) receptor
      blockade. 5) Aortas from the 40-wk-old rats had an increased expression of PGH
      synthase. Collectively, these observations indicate that, in the female rat, an
      increase in lipid peroxidation over time is associated with changes in
      endothelium-dependent vascular function that were due in part to a cyclooxygenase
      dependent vasoconstrictor.

PMID- 8997363
TI  - Intravenous infusion of insulin-like growth factor I in fetal sheep reduces
      hepatic IGF-I and IGF-II mRNAs.
AB  - Liver contains the highest concentrations of insulin-like growth factor (IGF) I
      mRNA in adult rats and sheep and is a major source of circulating IGF-I. In rats,
      inhibition of hepatic IGF-I production by exogenous IGF-I has been reported. In
      fetal sheep, skeletal muscle and liver are major sites of IGF-I synthesis and
      potential sources of circulating IGF-I. To determine whether feedback inhibition
      of IGF gene expression in fetal liver or muscle by IGF-I occurs, IGF-I and IGF-II
      mRNAs were measured in these tissues after intravenous infusion of recombinant
      human IGF-I into fetal sheep. Infusion of IGF-I (26 +/- 4 micrograms.h-1.kg-1; n
      = 6) or saline (n = 6) commenced on day 120 of pregnancy (term = 150 days) and
      continued for 10 days. Plasma concentrations of IGF-I were threefold higher in
      infused fetuses at 130 days of gestation (P < 0.0003), whereas those of IGF-II
      were unchanged. IGF-I infusion reduced the relative abundance of IGF-I mRNA (P <
      0.0002) and IGF-II mRNA (P < 0.01) in fetal liver by approximately 50% but did
      not alter IGF-I or IGF-II mRNA in skeletal muscle. These results indicate that
      IGF-I inhibits the expression of both IGF-I and IGF-II genes in fetal liver and
      that IGF gene expression in fetal liver and muscle is differentially regulated by
      IGF-I.

PMID- 8997365
TI  - Arginine vasopressin modulation of arterial baroreflex responses in fetal and
      newborn sheep.
AB  - The present study was designed to test the hypothesis that the influence of
      circulating vasopressin (AVP) on the arterial baroreflex control of renal
      sympathetic nerve activity (RSNA) and heart rate (HR) changes during development.
      To test this hypothesis, we studied arterial baroreflex-mediated control of HR
      and RSNA in the presence of increasing plasma levels of AVP in conscious,
      chronically instrumented fetal, newborn, and adult sheep. In fetal and newborn
      sheep, increasing plasma AVP levels (from < 10 to > 200 microU/ml) increased
      resting levels of mean arterial blood pressure (MABP) and decreased HR and RSNA.
      HR and RSNA baroreflex responses to variations of MABP with nitroprusside and
      phenylephrine infusion were not modified by elevated AVP levels in either newborn
      or fetal sheep, except for a small decrease in maximal HR response to
      nitroprusside infusion in the newborn animals. In contrast, in adults, AVP caused
      bradycardia and a decrease in RSNA without change in MABP, accompanied by
      resetting of the arterial baroreflex (decrease in maximal HR and RSNA, decrease
      in RSNA gain, and shift of HR to lower pressure). To test the hypothesis that the
      inability of AVP to reset the arterial baroreflex early during development was
      not secondary to maximal stimulation of V1 receptors during baseline conditions,
      we investigated the effect of V1-receptor blockade on baseline cardiovascular and
      arterial baroreflex function in newborn lambs. Administration of a V1-receptor
      antagonist produced no significant changes in resting MABP, HR, and RSNA and did
      not influence arterial baroreflex-mediated changes in HR and RSNA. These results
      indicate that, contrary to adults, circulating AVP does not modulate the arterial
      baroreflex in fetal and newborn sheep.

PMID- 8997364
TI  - Lysine acetylsalicylate modifies aphagia and thermogenic changes induced by
      lateral hypothalamic lesion.
AB  - These experiments test the effect of intraperitoneal injection of lysine
      acetylsalicylate on 1) food intake and 2) the sympathetic and thermogenic changes
      induced by lesion of the lateral hypothalamus (LH). Food intake, firing rate of
      the nerves innervating interscapular brown adipose tissue (IBAT), and IBAT and
      colonic temperatures (TIBAT and TC) were monitored in male Sprague-Dawley rats
      lesioned in the LH. These variables were measured before and after
      intraperitoneal injection of lysine acetylsalicylate. The same variables were
      also monitored in 1) lesioned rats with intraperitoneal administration of saline,
      2) sham-lesioned animals with intraperitoneal injection of lysine
      acetylsalicylate, and 3) sham-lesioned rats with intraperitoneal injection of
      saline. The results show that lysine acetylsalicylate modifies the aphagia by
      increasing food intake and also reduces the enhancements in firing rate, TIBAT,
      and TC induced by LH lesion. These findings suggest that prostaglandin synthesis
      plays a key role in the control of eating behavior in LH-lesioned rats by acting
      on the sympathetic and thermogenic changes induced by LH lesion.

PMID- 8997366
TI  - Chronic infusion of islet amyloid polypeptide causes anorexia in rats.
AB  - Islet amyloid polypeptide (IAPP) is a hormonal peptide that at high doses has
      been shown to reduce food intake. In the present study, the dose-response effects
      of subcutaneous infusion of IAPP (0, 2, 7, and 25 pmol.kg-1.min-1) for 8 days on
      food intake and meal patterns in rats were investigated. At the end of the
      experiment, plasma was obtained and levels of IAPP were measured by
      radioimmunoassay. IAPP dose-dependently and transiently inhibited food intake.
      The minimal effective dose (2 pmol.kg-1.min-1) caused a small but significant (up
      to 14%, P < 0.01) inhibition of food intake that lasted 5 days. The highest dose
      administered (25 pmol.kg-1.min-1) had the greatest effect (up to 44%, P < 0.001),
      which lasted throughout the 8-day period. Reductions in feeding during light and
      dark phases occurred through a decrease in number of meals consumed rather than
      meal size or meal duration. IAPP also decreased body weight gain and water intake
      dose dependently. IAPP infusion of 2, 7, and 25 pmol.kg-1.min-1 increased plasma
      IAPP concentrations from a basal level of 10.3 +/- 0.7 pM to 35.1 +/- 5.4, 78.1
      +/- 11.2, and 236.6 +/- 23.6 pM, respectively, values that are likely to be close
      to physiological and within the pathophysiological ranges. Thus IAPP may play an
      important physiological or pathophysiological role in control of food intake.

PMID- 8997368
TI  - IL-1 type I receptor mediates acute phase response to turpentine, but not
      lipopolysaccharide, in mice.
AB  - This study examined the role of the interleukin-1 (IL-1) type I receptor (IL
      1RtI) in the acute phase response (APR) to inflammation in mice. Turpentine (100
      microliters/mouse) injected subcutaneously induced fever, lethargy, body weight
      loss, and anorexia in IL-1RtI wild-type mice. Knockout mice lacking the IL-1RtI
      were resistant to these effects of turpentine, supporting a role for this
      receptor in the APR to local inflammation. The intraperitoneal injection of a low
      (50 micrograms/kg) or high (2.5 mg/kg) dose of lipopolysaccharide (LPS) induced
      similar APRs in IL-1RtI wild-type and knockout mice. IL-1RtI knockout mice were
      resistant to the APR induced by peripherally injected murine IL-1 beta,
      suggesting that it is not the interaction of endogenous IL-1 beta with IL-1RtII
      that induces an APR to LPS in these mice. We speculate that the absence of IL
      1RtI in these knockout mice results in the sensitization of other cytokine
      pathways to mediate the APR to LPS.

PMID- 8997367
TI  - Decreased total ventricular and mitochondrial protein synthesis during extended
      anoxia in turtle heart.
AB  - The turtle heart provides a model system to study the effects of anoxia on
      protein synthesis without the potentially confounding factor of contractile
      failure and decreased ATP levels. Protein synthesis, as measured by 3H-labeled
      phenylalanine incorporation, was studied under conditions of normoxia and anoxia
      in isolated perfused turtle [Trachemys (= Pseudemys) scripta elegans] hearts at
      15 degrees C. Heart rate, cardiac output, and ventricular pressure development
      were unaffected by 2 or 3 h of anoxia. Despite the anoxia, energy levels in the
      heart were presumably still high, since contractility was maintained. RNA content
      of ventricle decreased after anoxic perfusion. Rates of total protein synthesis
      rates in ventricle were threefold lower under anoxia than under normoxia. These
      findings suggest that the total level of RNA is one determinant of protein
      synthesis. Incorporation of label into protein extracted from mitochondria was
      also assessed. The ratio of mitochondrial to whole ventricular protein synthesis
      was significantly lower after anoxia, revealing preferential control mechanisms
      under anoxia between the synthesis of total cellular protein and protein destined
      for mitochondria. Isolated mitochondria were still coupled after 2 or 3 h of
      anoxia. In effect, the mitochondria enter into a state of hypometabolism in terms
      of rates of ATP synthesis and protein synthesis, but functional integrity is
      maintained. The decrease in protein synthesis in general and mitochondrial
      protein synthesis in particular may represent an adaptation to allow the
      partitioning of the available energy resources toward mechanical function during
      anoxia.

PMID- 8997369
TI  - Vectorial efflux of cGMP and its dependence on sodium in the cortical collecting
      duct.
AB  - Guanosine 3',5'-cyclic monophosphate (cGMP) is an important second messenger that
      regulates transport in the nephron. We propose that the transport mechanisms that
      remove cGMP from the cell are different in the luminal and basolateral membranes
      of the cortical collecting duct (CCD). We examined efflux of cGMP from cultured
      and isolated perfused CCDs in response to atrial natriuretic factor (ANF) and
      nitric oxide (NO). In the presence of phosphodiesterase inhibition, these
      compounds resulted in preferential efflux of cGMP across the basolateral membrane
      in both cultured and isolated CCDs. In the presence of ANF, efflux was five times
      higher across the basolateral than the luminal membrane in cultured CCD cells (n
      = 14). In isolated CCDs, effluxes across the basolateral and luminal membranes
      were 1.02 +/- 0.2 and 0.03 +/- 0.01 fmol.mm-1.min-1, respectively, in the
      presence of ANF (n = 6; P < 0.007) and 0.87 +/- 0.21 and 0.02 +/- 0.01 fmol.mm
      1.min-1, respectively, in the presence of NO (n = 6; P < 0.011). Efflux across
      the basolateral membrane in the presence and absence of sodium was 37 +/- 7.3 and
      19.9 +/- 5 fmol.cm-2.min-1, respectively, in cultured cells (n = 12; P < 0.044)
      and 1.02 +/- 0.2 (n = 6) and 0.41 +/- 0.12 (n = 5) fmol.mm-1.min-1 in isolated
      perfused tubules (P < 0.042). There was no difference in luminal transport in the
      presence and absence of sodium in either model. We conclude that there are at
      least two different mechanisms involved in the removal of cGMP from the cell, one
      sodium dependent and the other sodium independent. The basolateral membrane
      appears to contain both, whereas the luminal membrane contains only the sodium
      independent mechanism.

PMID- 8997370
TI  - Measurement of tissue volume during non-steady state high-intensity muscle
      contraction.
AB  - To investigate the pressures driving water into stimulated muscle, water
      distribution during and after muscle stimulation was studied in isolated cat
      muscles perfused by recirculating diluted blood. 51Cr-labeled EDTA (51Cr-EDTA)
      and Evans blue-labeled albumin were used to determine extracellular volume and
      plasma volume (PV), respectively. Change in tissue volume was calculated as -PV.
      Interstitial volume (IFV) was determined from the ratio of interstitial solute
      (51Cr-EDTA and sodium) mass and interstitial concentration. Interstitial mass was
      determined by mass balance, and interstitial concentration was determined from
      solute flux and Fick's Law. One group was stimulated at 4 Hz for 2 min, and a
      second was stimulated by 80-Hz trains (1 train/s, 0.1 s duration). Four Hertz
      stimulation increased total tissue volume by approximately 3 ml/100 g and
      decreased IFV by 1 ml/100 g. Train stimulation increased total tissue volume by 6
      ml/100 g and decreased IFV by 4. These data indicate that water moves into cells
      faster than the simultaneous transcapillary flow, suggesting that intracellular
      osmoles provide the primary driving pressure in stimulation-induced swelling.

PMID- 8997371
TI  - Responses of fetal sheep to reduced maternal renal blood flow and maternal
      hypertension.
AB  - In 16 chronically catheterized fetal sheep the effects of reducing and restoring
      maternal renal blood flow (RBF) and thus inducing and reversing hypertension were
      studied in uninephrectomized pregnant ewes; controls were 3 fetuses that were
      carried by uninephrectomized ewes in which RBF was not reduced and that did not
      become hypertensive. Within 24-72 h of maternal RBF reduction, fetal arterial PO2
      had fallen (P < 0.001) and PCO2 had increased (P < 0.025); fetal arterial
      pressure also increased (P < 0.005). These effects persisted, despite restoration
      of maternal RBF and reversal of maternal hypertension. Within 24-72 h of
      reduction of maternal RBF, fetal urine flow had increased (P < 0.005), and it
      remained elevated over the first 3 h after RBF was restored; 24-72 h later it was
      lower (P < 0.025) and returned to control levels. The excretion of sodium,
      potassium, and chloride showed a similar increase when maternal RBF was reduced
      (P < 0.001), with return to control values 24-72 h after RBF had been restored.
      Fetal glomerular filtration rate did not change; thus the natriuresis and
      diuresis that occurred were due to reduced tubular solute and water reabsorption
      (P < 0.025). These changes in fetal renal function may be related, in part, to
      changes in fetal PO2 and PCO2, but they are most likely due to reduced maternal
      renal function due to the restriction in maternal RBF, inasmuch as they were
      reversed when RBF was restored.

PMID- 8997372
TI  - Mechanisms of maternofetal chloride transfer across the human placenta perfused
      in vitro.
AB  - To determine the relative contribution of the paracellular and transcellular
      routes to Cl-transfer, unidirectional maternofetal clearance (Kmf) of 36Cl was
      compared with Kmf of 51Cr-EDTA and creatinine across the human placenta perfused
      in vitro. The effect of C1-transport inhibitors 4,4'-diisothiocyanostilbene-2,2
      disulfonic acid (DIDS) and diphenylamine-2-carboxylate (DPC) was also
      investigated. The diffusion coefficient (D) was estimated for each solute by use
      of an agar diffusion method. At steady state, Kmf/D for 36Cl (0.070 +/- 0.003 cm,
      n = 23) was not different from that for 51Cr-EDTA (0.070 +/- 0.003 cm, n = 23),
      and Kmf/D was significantly higher for creatinine than for 36Cl and 51Cr-EDTA
      (0.087 +/- 0.003 cm, n = 20, P < 0.001). Addition of the inhibitors DIDS and DPC
      to the perfusates resulted in a small but significant rise in Kmf of 51Cr-EDTA
      (0.41 +/- 0.03 vs. 0.49 +/- 0.02 ml/min, n = 16, P < 0.0001) and creatinine (0.66
      +/- 0.05 vs. 0.74 +/- 0.04 ml/min, n = 13, P < 0.001), but Kmf of 36Cl was
      unchanged (1.11 +/- 0.07 vs. 1.13 +/- 0.05 ml/min, n = 16). There was no change
      in Kmf of any solute with time in control experiments. From these data, DIDS- and
      DPC-inhibitable fractions of Kmf for 36Cl were estimated and together accounted
      for 16% of total clearance. This study suggests that maternofetal flux of 36Cl
      across the in vitro perfused human placenta occurs predominantly, but not solely,
      via paracellular routes.

PMID- 8997373
TI  - GABA release in posterior hypothalamus across sleep-wake cycle.
AB  - The activity of neurons in the posterior hypothalamus (PH) is thought to
      contribute to the production of wakefulness and electroencephalograph
      desynchronization. Inactivation of neuronal activity in this area is known to
      induce sleep. Most PH neurons decrease unit discharge during slow-wave sleep
      (SWS) relative to wake and rapid eye movement sleep. In the present study, we
      sought to examine potential sources of inhibition or disfacilitation underlying
      the reduction of PH unit activity during SWS in the cat. We employed the
      microdialysis technique in conjunction with high-performance liquid
      chromatography methods for the quantification of glutamate, glycine, and gamma
      aminobutyric acid (GABA) release. We found a selective increase in GABA release
      during SWS in the PH. Glutamate and glycine levels were unchanged across the
      sleep-wake cycle. microinjection of the GABAA-receptor agonist muscimol, into the
      same areas from which microdialysis samples were collected, increased SWS time.
      Our studies support the hypothesis that GABA release in the posterior
      hypothalamus mediates inhibition of posterior hypothalamic neurons, thereby
      facilitating SWS.

PMID- 8997375
TI  - Stimulation of aortic nerve evokes three different response patterns in neurons
      of rostral VLM of the rat.
AB  - Because the aortic nerve of the rat is believed to contain only barosensory
      fibers in a functionally significant number, stimulation of this nerve provides a
      convenient means to identify barosensitive neurons in the central nervous system.
      The aim of the present study was to describe the characteristics of responses to
      stimulation of the aortic nerve in the neurons of the ventrolateral medulla
      oblongata (VLM) from in vivo intracellular recordings. Data were obtained from 25
      neurons that were either spontaneously active and exhibited pulse-synchronous
      discharge or were silent. Cells that showed a regular increase in their discharge
      rate during diastole responded with either an inhibitory postsynaptic potential
      (IPSP, group 1; n = 3) or a biphasic excitatory postsynaptic potential (EPSP)
      IPSP (group 2; n = 10) to aortic nerve stimulation. Parameters of the inhibitory
      response were similar in both groups (27 +/- 2 and 31 +/- 2 ms for onset latency
      and 55 +/- 10 and 67 +/- 7 ms in duration, respectively). In group 2 cells, the
      inhibition was, however, preceded by a brief excitation (14 +/- 2 ms for onset
      latency and 13 +/- 1 ms in duration). Group 3 neurons, which showed a regular
      increase in their discharge rate during or before systole (n = 7), responded with
      an EPSP (20 +/- 2 ms for onset latency and 44 +/- 5 ms in average duration).
      Group 1 and 3 responses were also encountered in quiescent neurons (n = 5).
      Intracellular labeling revealed that neurons of all three types were localized
      within the rostral VLM. The functional significance of these findings is
      discussed.

PMID- 8997374
TI  - Functional evidence for L-type Ca2+ channels controlling ANG II-induced adrenal
      catecholamine release in vivo.
AB  - The aim of the present study was to investigate the functional involvement of L-
      and/or N-type Ca2+ channels in adrenal catecholamine secretion in response to
      exogenous angiotensin II (ANG II) in anesthetized dogs. Plasma catecholamine
      concentrations in adrenal venous and aortic blood were determined by a high
      performance liquid chromatography-electrochemical method. In the first series of
      experiments, repeated infusions of BAY K 8644 locally into the left adrenal gland
      at 15-min intervals resulted in significant and reproducible increases in adrenal
      catecholamine secretion. Nifedipine, similarly administered 5 min before BAY K
      8644, diminished BAY K 8644-induced catecholamine secretion in a dose-dependent
      manner and completely blocked the catecholamine response at the highest dose
      tested. In the second series of experiments, local infusion of ANG II resulted in
      a significant increase in adrenal catecholamine secretion. The maximum
      catecholamine response to ANG II was attenuated by approximately 65% in the
      presence of nifedipine at the dose that abolished the BAY K 8644-induced
      catecholamine release. This inhibition by nifedipine remained unchanged in the
      presence of omega-conotoxin. The present study shows that dihydropyridine
      sensitive L-type Ca2+ channels are operative in the adrenal medulla of the dog in
      vivo. The results indicate that the L-type Ca2+ channels are only partially
      implicated in the local regulation of ANG II-induced adrenal catecholamine
      secretion, suggesting the existence of another mechanism. However, omega
      conotoxin-sensitive N-type Ca2+ channels are unlikely to be functionally involved
      in postsynaptic mechanisms mediating adrenal catecholamine secretion in response
      to exogenous ANG II under in vivo conditions.

PMID- 8997376
TI  - Beta 3-adrenoceptor in guinea pig brown and white adipocytes: low expression and
      lack of function.
AB  - In the guinea pig, cold acclimation induced a conversion of unilocular to
      multilocular adipocytes in interscapular (IS) and retroperitoneal (RP) fat depots
      but not in the epididymal (EP) fat pad. The conversion was associated with an
      increase in mitochondriogenesis and the appearance of the uncoupling protein. The
      maximal lipolytic responses to norepinephrine and dibutyryl adenosine 3',5'
      cyclic monophosphate were decreased in IS cells, unchanged in RP cells, and
      increased in EP cells, suggesting a site-specific regulation of lipolysis at the
      postreceptor level. beta 3-Adrenergic agonists were not lipolytic regardless of
      the depot and the thermal environment of the animal. These agents did not inhibit
      glucose transport and lipogenesis, as was previously reported for rodents.
      Cloning and sequencing of the guinea pig beta 3-adrenoceptor gene revealed a
      slightly higher amino acid sequence similarity with the human than with the
      rodent beta 3-adrenoceptors. beta 3-Adrenoceptor transcripts were present at a
      very low level in guinea pig adipocytes, and mRNA levels did not increase to a
      significant extent after cold acclimation. The guinea pig thus differs from
      rodents by an absence of beta 3-adrenergic effects and by low beta 3-adrenoceptor
      expression in brown and white adipose tissues.

PMID- 8997377
TI  - Upregulation of endothelial and neuronal constitutive nitric oxide synthase in
      pregnant rats.
AB  - Pregnancy is characterized by hemodynamic and body fluid alterations. Increased
      nitric oxide (NO) production has been suggested to play a role in the hemodynamic
      alterations of pregnancy and has also been reported to increase arginine
      vasopressin (AVP) release. We therefore hypothesized that gestation could
      increase both NO synthase (NOS) constitutive isoforms, neuronal NOS and
      endothelial NOS, and thereby contribute to the hyposmolality and peripheral
      arterial vasodilation of pregnancy, respectively. The present study was therefore
      undertaken to examine the constitutive NOS isoforms in aortas, mesenteric
      arteries, and hypothalami of pregnant rats on day 20 of gestation compared with
      age-matched nonpregnant rats. Plasma AVP was determined by radioimmunoassay and
      hypothalamic mRNA AVP by solution hybridization assay. Hypothalamic neuronal NOS
      was assessed by Northern blot and Western blot; endothelial NOS was assessed by
      Western blot in arteries and hypothalamus. The results demonstrated that 1)
      plasma AVP and hypothalamic AVP mRNA are increased in pregnant rats (n = 8), 2)
      neuronal NOS protein and mRNA are increased in hypothalamus of pregnant rats (n =
      4), and 3) endothelial NOS expression, as assessed by Western blot analysis, is
      increased in both conductance (aorta) as well as resistance (mesenteric) arteries
      of pregnant rats (n = 4). We conclude that both of the constitutive NOS isoforms
      are increased in pregnant rats, suggesting that the peripheral arterial
      vasodilation and hyposmolality of pregnancy could be mediated by these isoforms.

PMID- 8997378
TI  - Synergistic effect of acidification and hypoxia: in vivo 31P-NMR and
      respirometric study in fishes.
AB  - We used 31P nuclear magnetic resonance (31P-NMR) spectroscopy to measure
      intracellular pH (pHi) and high-energy phosphate levels of white muscle of the
      fish tilapia (Oreochromis mossambicus) during exposure to the stressors hypoxia
      and water acidification separately and simultaneously. The protocol for the
      graded hypoxia load was 100, 40, 30, 20, 10, 5, and 3% air saturation for 1 h at
      each level. For environmental acidosis the pH of the water was lowered from 7.6
      to 4.0 over 6 h, with time of exposure approximately 11 h. All protocols were
      followed by 6 h of reoxygenation at 20 degrees C. We also measured total oxygen
      consumption of the animal. The results of this in vivo study revealed that
      environmental acidification had no effect on oxygen consumption, pHi, or
      phosphocreatine depletion. Hypoxia caused moderate changes in these parameters
      and fast and complete recovery during reoxygenation. In contrast, the combination
      of environmental acidosis and hypoxia resulted in 50% mortality, increased
      depletion of the phosphocreatine pool, and a retarded recovery of the pHi during
      reoxygenation compared with the group with hypoxia as a single stressor. The
      combination of environmental acidification and hypoxia has a more profound effect
      and works synergistically compared with the conditions imposed separately. To
      investigate whether an adaptation response occurred during chronic exposure to
      environmental acidification, animals were exposed for 6 wk to pH 4.0 before
      experimentation. The pHi in the white muscle dropped from 7.2 (control group) to
      6.9 during this period, whereas no effect was found in the phosphorylated
      compounds and oxygen consumption. Therefore, it is concluded that no adaptation
      response occurs in animals exposed to long-term environmental acidosis.

PMID- 8997379
TI  - Body temperature and sleep in intact and ovariectomized female rats.
AB  - The present study examined intact and ovariectomized adult rats to assess the
      effects of removal of sex hormones on body temperature (Tb) and sleep. Subjects
      were 12 female rats, aged 5-8 mo, half of which were bilaterally ovariectomized
      (OVX). Sleep or waking and Tb were recorded under a 12:12-h light-dark cycle.
      There was a strong coupling between level of Tb and the three conditions of
      waking, slow-wave sleep (SWS), and rapid eye movement sleep (REMS): Tb was
      significantly positively correlated with waking and significantly negatively
      correlated with SWS and REMS. These correlations were even higher in OVX rats. In
      the light, OVX rats had more SWS and stayed awake less than did the intact rats.
      OVX rats had more REMS than did intact rats in both light and dark. Mean Tb and
      daily Tb amplitude were the same in both groups. These results suggest that
      ovariectomy increases and, by extension, gonadal steroids decrease, the coupling
      between Tb and sleep.

PMID- 8997380
TI  - Cardiac hypertrophy and telemetered blood pressure 6 wk after baroreceptor
      denervation in normotensive rats.
AB  - We investigated cardiac morphometry 6 wk after sinoaortic baroreceptor
      denervation (SAD) in Long-Evans rats. SAD (n = 19) was associated with an 11%
      increase in the weight of the left ventricle (LV) plus septum (P < 0.001) and a
      39% increase in that of the right ventricular (RV) free wall (P < 0.001),
      relative to sham-operated rats (n = 18). RV wall thickness was significantly
      increased in SAD animals, but there was no difference in the LV wall thickness
      and volumes of the RV and LV between groups. Constrictor responses to methoxamine
      and dilation responses to acetylcholine were assessed in an in vitro perfused
      mesenteric circulation preparation, but neither response was affected by SAD.
      Baroreceptor denervation was associated with marked and significant increases in
      the variability (2.8-fold) and daily peak (39 mmHg) levels of telemetered mean
      arterial pressure (MAP) and small (5%) but significant increases in the daily
      mean MAP level. Our results are consistent with an effect of increased MAP
      variability on ventricular weight but cannot rule out possible contributions from
      other mechanisms.

PMID- 8997381
TI  - Leptin reduces juvenile fat stores by altering the circadian cycle of energy
      expenditure.
AB  - The recently identified hormone leptin (ob protein) secreted by white adipose
      tissue is widely thought to provide a feedback signal limiting fat storage by
      decreasing food intake. By artificially rearing leptin-treated and control
      littermates fed identical amounts of milk, however, we show here that lean
      suckling-age rats treated with recombinant murine leptin can reduce fat storage
      solely by increasing energy expenditure. Continuous measurements of core
      temperature and metabolic rate show that this increase is not uniform throughout
      the day but is especially prominent in the morning when rat pups usually conserve
      energy by entering a torpor-like state. Leptin's alleviation of hypometabolic,
      torpor-like states is thus not restricted to cases of impaired hormone production
      but seems instead to be a normal biological function independent of its effects
      on food intake.

PMID- 8997382
TI  - Leptin inhibits prehibernation hyperphagia and reduces body weight in arctic
      ground squirrels.
AB  - The ob gene product leptin is thought to play a physiological role in the fine
      tuning of a homeostatic mechanism regulating satiety and adiposity. Mouse
      recombinant leptin was administered to seasonally hyperphagic arctic ground
      squirrels as a first step in demonstrating the evolutionary conservation of
      leptin function and the potential involvement of leptin in the seasonal
      regulation of adiposity in hibernators. Continuous infusion of leptin for 3 wk
      via miniosmotic pumps resulted in a reduction in food intake and body weight in a
      manner consistent with its proposed role as a satiety hormone. During the
      recovery period after leptin administration, squirrels that had received leptin
      became hyperphagic relative to controls. Percent body fat was estimated at weekly
      intervals by measuring total body electrical conductivity and decreased after 3
      wk of leptin administration. Our observations support the role of leptin as a
      regulatory hormone involved in the control of satiety, adiposity, and possibly
      energy expenditure in hibernating mammals.

PMID- 8997383
TI  - Growth factors and the kidney: regulation of epithelial cell movement and
      morphogenesis.
AB  - The control of epithelial cell movement and shape change is complex and requires
      regulation of a broad range of events including cell-cell adhesion contacts, cell
      substratum interactions, and the actin cytoskeleton. Utilizing the hepatocyte
      growth factor tyrosine kinase receptor, c-met, the present review examines how
      growth factor receptors activate intracellular signaling pathways, which can then
      regulate the events necessary for epithelial cells to disassemble their existing
      structure, undergo extensive shape change and cell body movement, and reassemble
      into a polarized epithelium. The role of growth factor-mediated activation of the
      phosphoinositide 3-kinase, phospholipase C-gamma, c-src family members, and ras
      family members is addressed in relation to integrin-mediated cell-basement
      membrane contacts, cadherin-mediated cell-cell adhesions, and regulation of the
      actin cytoskeleton.

PMID- 8997384
TI  - Effect of age on blood acid-base composition in adult humans: role of age-related
      renal functional decline.
AB  - In 64 apparently healthy adult humans (ages 17-74 yr) ingesting controlled diets,
      we investigated the separate and combined effects of age, glomerular filtration
      rate (GFR, index of age-related renal functional decline), renal net acid
      excretion [NAE, index of endogenous acid production (EAP)], and blood PCO2
      (PbCO2, index of respiratory set point) on steady-state blood hydrogen ion
      ([H+]b) and plasma bicarbonate concentration ([HCO3-]p). Independent predictors
      of [H+]b and [HCO3-]p were PbCO2, NAE, and either age or GFR, but not both,
      because the two were highly correlated (inversely). [H+]b increased with
      increasing PbCO2, NAE, and age and with decreasing GFR. [HCO3-]p decreased with
      increasing NAE and age but increased with increasing PbCO2 and GFR. Age (or GFR)
      at constant NAE had greater effect on both [H+]b and [HCO3-]p than did NAE at
      constant age (or GFR). Neither PbCO2 nor NAE correlated with age or GFR. Thus two
      metabolic factors, diet-dependent EAP and age (or GFR), operate independently to
      determine blood acid-base composition in adult humans. Otherwise healthy adults
      manifest a low-grade diet-dependent metabolic acidosis, the severity of which
      increases with age at constant EAP, apparently due in part to the normal age
      related decline of renal function.

PMID- 8997385
TI  - Asymmetry of tubuloglomerular feedback effector mechanism with respect to ambient
      tubular flow.
AB  - The contribution of preglomerular resistance changes to the tubuloglomerular
      feedback (TGF) effector response was evaluated by micropuncture in hydropenic
      rats. Studies were performed in free-flowing nephrons to compare the fractional
      compensation (C) for perturbations in late proximal flow (VLP) with associated
      changes in glomerular capillary hydrostatic pressure (PGC). VLP was monitored by
      a noninvasive optical technique, and PGC was monitored by direct capillary
      micropuncture. Data were employed in conjunction with a model of glomerular
      filtration to analyze the TGF effector mechanism. C varied with the applied
      perturbation (VH), showing a single peak near the natural operating point. In
      contrast, the effect of TGF on PGC was asymmetric about the operating point, such
      that PGC was sensitive only to large positive perturbations. The model predicts
      that changes in preglomerular resistance account for only a small fraction of the
      integrated TGF response to small disturbances in the ambient state of the nephron
      but account for a greater share of the response to larger increments in flow. The
      TGF response in hydropenic rats is mediated by both pre- and postglomerular
      vascular elements.

PMID- 8997386
TI  - Distribution of binding sites for thromboxane A2 in the mouse kidney.
AB  - Thromboxane A2 (TxA2) is a potent vasoconstrictor eicosanoid that has been
      implicated in the pathogenesis of both human and experimental renal diseases. The
      biological actions of TxA2 in the kidney are mediated through specific cell
      surface receptors. In this report, we characterize the distribution of
      thromboxane receptors (TxR) within the normal mouse kidney by receptor
      autoradiography. With the iodinated TxR agonist [125I]BOP, TxA2 binding sites
      were detected throughout the kidney. Competitive inhibition curves of whole
      kidney binding demonstrated a half-maximal inhibitory concentration of 6.5 nM.
      When Scatchard analysis was performed on anatomically discrete regions, the
      [125I]BOP binding in the medulla was best fit by a one-site model, with a
      dissociation constant (Kd) of 8.2 +/- 2.2 nM. In contrast, [125I]BOP binding in
      the cortex was better described by a two-site model, with estimated Kd of 262 +/-
      16 pM for a higher affinity site and 16.9 +/- 1.3 nM for a lower affinity site.
      These sites do not appear to represent receptor isoforms that arise from
      alternative splicing of mRNA. The lower affinity binding sites may represent a
      novel TxR or an alternative affinity state for the previously characterized high
      affinity binding site.

PMID- 8997387
TI  - Parathyroid hormone-induced calcium efflux from cultured bone is mediated by
      protein kinase C translocation.
AB  - Activation of adenylate cyclase is believed to be the major intracellular
      mediator of bone resorption induced by parathyroid hormone (PTH), prostaglandins,
      and various bone resorbing cytokines. Studies have demonstrated a dissociation
      between PTH-induced bone resorption and adenosine 3',5'-cyclic monophosphate
      (cAMP) formation, as well as suggested a role of protein kinase C (PKC) in
      mediating in part the actions of PTH. We therefore investigated the relative
      contribution of the adenylate cyclase or PKC signal transduction pathways in
      mediating the PTH-induced net calcium release from cultured neonatal calvariae,
      an in vitro model of bone resorption. PTH (10(-11) to 10(-7) M) caused a dose
      dependent increase in calcium efflux from cultured bone and activated both cAMP
      and PKC. To determine the role of each of these second messengers in mediating
      PTH-induced calcium release from bone, calvariae were preincubated with either
      the adenylate cyclase inhibitor SQ-22536 (10(-5) to 10(-4) M) or the PKC
      inhibitor staurosporine (10(-7) M) before coincubation with PTH. Compared with
      control, PTH caused a significant calcium efflux, whereas preincubation with SQ
      22536 had no effect on basal calcium efflux and partially inhibited the calcium
      efflux caused by PTH. In contrast preincubation with staurosporine completely
      obliterated the PTH-induced calcium efflux. PTH is a potent stimulator of calcium
      release and activates both the cAMP and PKC signal transduction pathways in
      cultured bone. Inhibition of PTH-stimulated PKC activity completely abolished the
      PTH-induced calcium efflux from calvariae, whereas PTH-induced calcium efflux
      persisted despite adenylate cyclase inhibition. Thus the bone resorbing effect of
      PTH appears to be dependent predominantly on activation of PKC.

PMID- 8997388
TI  - Immortalized rabbit cortical collecting duct cells express AT1 angiotensin II
      receptors.
AB  - Rabbit cortical collecting duct (CCD) cells were immortalized to study
      angiotensin II (ANG II) signaling in the CCD. Transfected cells retained CCD
      properties; arginine vasopressin (AVP), prostaglandin E2, and isoproterenol (10(
      7) M) all significantly stimulated adenosine 3',5'-cyclic monophosphate (cAMP)
      production; and parathyroid hormone and calcitonin had no effect on cAMP. Twenty
      seven percent of transfected cells bound the beta-intercalated cell marker peanut
      lectin agglutinin, whereas antibodies against principal cells and alpha
      intercalated cells immunolabeled 26% of cells. All cells stained with antibodies
      to the epithelial cell marker cytokeratin. By contrast, no immunofluorescence was
      observed with antibodies to smooth muscle myosin, Tamm-Horsfall protein, or
      factor VIII. Transfected cells demonstrated amiloride-sensitive transepithelial
      short-circuit current. In transfected cells, radioligand binding assays detected
      a single class of ANG II receptors (affinity constant = 0.78 nM), and AT1
      receptor mRNA was demonstrated by Northern analysis. ANG II (10(-7) M)
      significantly inhibited AVP-stimulated cAMP production; lower concentrations (10(
      10) M) increased phosphoinositide hydrolysis. In summary, we immortalized a
      rabbit CCD cell line that retains characteristic morphological and hormonal
      properties. These cells express AT1 receptors, coupled to inhibition of cAMP and
      to stimulation of phosphoinositide turnover. We postulate that these signaling
      pathways may mediate effects of ANG II on CCD transport and cell growth.

PMID- 8997389
TI  - cGMP-activating peptides do not regulate electrogenic electrolyte transport in
      principal cells of rat CCD.
AB  - K+ channels in the basolateral membrane of rat cortical collecting duct (CCD) are
      regulated by a cGMP-dependent protein kinase (J. Hirsch and E. Schlatter.
      Pfluegers Arch. 429: 338-344, 1995). Conflicting data exist on the effects of
      cGMP-activating agonists on Na+ transport in these cells. Thus we tested members
      of the family of peptides that increase intracellular cGMP [cardiodilatin/atrial
      natriuretic peptide (CDD/ANP), brain natriuretic peptide, C-type natriuretic
      peptide, urodilatin, guanylin, and uroguanylin], as well as bradykinin +/-
      CDD/ANP on membrane voltages (Vm) of principal cells of isolated rat CCD using
      the slow whole cell patch-clamp technique (E. Schlatter, U. Frobe, and R. Greger.
      Pfluegers Arch. 421: 381-387, 1992). None of the agonists tested changed Vm
      significantly. There was also no effect of dibutyryl guanosine 3',5'-cyclic
      monophosphate (DBcGMP) on AVP-dependent lumen-to-bath Na+ flux, transepithelial
      voltage, or osmotic water permeability in isolated perfused rat CCD. Finally,
      CDD/ANP increased intracellular cGMP only in glomeruli but not in CCD. Thus the
      findings provide no evidence for control of electrogenic electrolyte transport by
      these natriuretic peptides in principal cells of rat CCD, and the agonist that
      physiologically regulates the cGMP-dependent K+ channels remains to be
      identified.

PMID- 8997390
TI  - Differential regulation of renal regional blood flow by endothelin-1.
AB  - The present study evaluated the effects and mechanisms of action of endothelin-1
      (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively). CBF and
      MBF were measured simultaneously by laser-Doppler flowmetry in anesthetized male
      Wistar rats. Bolus injection of ET-1 (1.0 nmol/kg iv) produced a sustained
      decrease in CBF (delta = -30%) and a transient increase in MBF (delta = +35%).
      The medullary vasodilation induced by ET-1 was observed with doses lower than
      that required to produce cortical vasoconstriction; was completely blocked by
      bosentan, a mixed ETA/B-receptor antagonist; and was mimicked by IRL-1620, a
      specific ETB-receptor agonist. In contrast, BQ-123, an ETA-receptor antagonist,
      failed to inhibit the ET-1-dependent medullary vasodilation but effectively
      blocked the cortical vasoconstriction induced by the peptide. Finally, inhibition
      of nitric oxide (NO) synthase completely abolished, whereas cylooxygenase
      inhibition attenuated, the effect of ET-1 on MBF. The data demonstrate that ET-1
      exerts opposite effects on renal cortical and medullary circulation, i.e., ETA
      receptor-mediated cortical vasoconstriction and ETB-mediated medullary
      vasodilation. Furthermore, the medullary vasodilation induced by ET-1 is
      dependent on the NO system and, to a lesser extent, on prostaglandin generation.

PMID- 8997391
TI  - Multiple pathways of organic anion secretion in renal proximal tubule revealed by
      confocal microscopy.
AB  - Previous studies with p-aminohippurate (PAH) and fluorescein (FL) have shown that
      cellular uptake and tubular secretion of organic anions is driven by indirect
      coupling to sodium. Here we used killifish proximal tubules and laser-scanning
      confocal microscopy to study the transport of a larger organic anion, fluorescein
      methotrexate (FL-MTX, mol mass 923 Da). When tubules were incubated in medium
      containing 2 microM FL-MTX, dye accumulated in both cells and tubular lumens. At
      steady state, luminal fluorescence was 4-5 times higher than cellular
      fluorescence. Ouabain (0.1 mM) did not affect cellular or luminal fluorescence,
      and replacement of medium sodium by N-methylglucamine had only a modest effect;
      preincubation with glutarate had no effect. KCN did not affect cellular uptake
      but abolished secretion into the lumen. Uptake and secretion of FL-MTX were
      inhibited by micromolar concentrations of other organic anions (MTX, folate,
      probenecid, bromocresol green, bromosulfophthalein), but 1 mM PAH had a
      relatively small effect. FL-MTX secretion into the lumen was inhibited by
      leukotriene C4, cyclosporine A, and verapamil, none of which affected FL
      transport. Thus a substantial component of FL-MTX secretion is Na independent and
      ouabain insensitive. Both the basolateral and luminal steps in the Na-independent
      pathway differ from those usually associated with FL and PAH secretion.

PMID- 8997392
TI  - Prostacyclin increases distal tubule HCO3 secretion in the rat.
AB  - We examined whether prostacyclin (PGI2), a prostaglandin synthesized in the renal
      cortex that increases adenosine 3',5'-cyclic monophosphate levels in distal
      nephron epithelia, mediates increased HCO3 secretion in in vivo perfused distal
      tubules of anesthetized rats given dietary HCO3. Animals eating a minimum
      electrolyte diet given 80 mM NaHCO3 drinking solution increased urine excretion
      of 6-keto-PGF1 alpha, a PGI2 metabolite, by 2.6 +/- 0.3-fold compared with those
      drinking distilled H2O. NaHCO3 animals infused with indomethacin to inhibit PGI2
      synthesis had lower HCO3 secretion than those without indomethacin (-8.9 +/- 0.9
      vs. -18.7 +/- 1.8 pmol.mm-1.min-1, P < 0.01). By contrast, NaHCO3 animals infused
      with both PGI2 and indomethacin had higher HCO3 secretion than those given
      indomethacin alone (-16.0 +/- 1.5, P < 0.02 vs. indomethacin group). HCO3
      secretion was not different between controls with and without indomethacin but
      was higher in the PGI2 + indomethacin compared with the indomethacin alone
      controls (-11.2 +/- 1.2 vs. -4.5 +/- 0.5, P < 0.01). The data show that PGI2
      increases distal tubule HCO3 secretion in rats and suggest that this agent
      contributes to the increased distal tubule HCO3 secretion induced by dietary
      HCO3.

PMID- 8997393
TI  - Regulation of Fas and Fas ligand expression in cultured murine renal cells and in
      the kidney during endotoxemia.
AB  - Fas ligand (FasL) and Fas belong to a recently described family of cytokines and
      receptors with similarities to tumor necrosis factor (TNF) and its receptors.
      Upon engagement by specific antibodies or by FasL, Fas transduces a signal for
      apoptosis in permissive cells. Although apoptosis occurs during renal development
      and following injury to mature cells, the factors responsible for programmed
      renal cell death are uncertain. We have studied Fas expression by renal cells in
      vitro and during endotoxemia in mice. Several renal cell types, including
      glomerular mesangial cells and tubular epithelial cells express a Fas transcript
      in culture. Lipopolysaccharides (LPS), interleukin-1 beta, interferon-gamma (IFN
      gamma), and TNF-alpha increase the levels of Fas mRNA in cultured mesangial and
      tubular cells. TNF-alpha and LPS raise the level of Fas mRNA in a time- and dose
      dependent manner with Fas receptor expression peaking after 72 h of exposure to
      LPS. Anti-Fas antibodies can induce the death of cultured mesangial cells. This
      cell death shows the characteristic changes of apoptosis, including DNA
      fragmentation and pyknotic changes of the nucleus. Increases in Fas by LPS, TNF
      alpha, and IFN-gamma enhance the killing induced by the anti-Fas antibody. FasL
      is also expressed by cultured renal cells, and TNF-alpha treatment of mesangial
      cells increases its expression. In vivo, Fas mRNA is present at low level in
      normal kidney. LPS increases the levels of Fas mRNA and protein in kidney and
      produces evidence of apoptosis along nephrons. These data suggest that
      transcripts encoding natural FasL and Fas are induced by LPS and may play a role
      in endotoxemia-induced acute renal failure and organ dysfunction.

PMID- 8997394
TI  - In vivo and in vitro evidence for increased expression of HGF receptor in kidney
      of diabetic rat.
AB  - Renal hypertrophy develops early in the course of diabetes and has been linked to
      progressive renal disease. Although the mechanism of renal hypertrophy is
      unknown, evidence suggests that local alterations in the production of one or
      more growth factors and/or their receptors are crucial to this process. In this
      study, we demonstrate that the c-met protooncogene product, a tyrosine kinase
      receptor for hepatocyte growth factor (HGF), is increased in the kidney of the
      diabetic rat. Northern blot analysis showed that renal expression of the c-met
      gene was substantially increased in rats made diabetic by administration of
      streptozotocin. Immunohistochemical studies revealed that the protein for c-met
      was concordantly elevated in cortical and medullar tubular epithelium following
      the onset of diabetes. Moreover, in vitro studies demonstrated that short-term
      exposure to high glucose concentration markedly stimulated c-met expression in
      cultured proximal tubular (opossum kidney) and inner medulla collecting duct
      cells (mIMCD-3). The results of enhanced renal expression of c-met together with
      elevated HGF indicate that the HGF/c-met system is markedly activated in the
      diabetic rat. These findings suggest that the HGF/c-met system may play a role in
      the diabetic renal hypertrophy.

PMID- 8997395
TI  - The p53-independent activation of transcription of p21 WAF1/CIP1/SDI1 after acute
      renal failure.
AB  - In three different models of acute renal failure (ischemia, ureteral obstruction,
      and cisplatin administration), the p21WAF1/CIP1/SDI1 gene, the protein product of
      which is associated with cell-cycle interruption, terminal differentiation, and
      cellular senescence, was activated in murine kidney cells. This transcription was
      localized in kidney only to cells of thick ascending limbs and distal convoluted
      tubules. Although the tumor suppressor protein, p53, can trans-activate the p21
      gene in some cells, increased levels of nuclear p53 protein could be demonstrated
      only in the cisplatin model of acute renal failure. High levels of p21 mRNA were
      induced in kidney of p53 "null" mice, demonstrating that p21 gene activation was
      through a p53-independent pathway. We also present evidence that, in the
      cisplatin model, both p53-independent and p53-dependent induction of p21 mRNA
      occur simultaneously. We conclude that p21 gene activation is a general response
      to renal injury and could be a key determinant of cell fate in the cell in which
      it is expressed.

PMID- 8997396
TI  - Calcitonin stimulates H+ secretion in rat kidney intercalated cells.
AB  - Calcitonin (CT) modulates rat intercalated cell (IC) functions of the rat
      cortical collecting duct (CCD) [E. Siga, B. Mandon, N. Roinel, and C. de
      Rouffignac. Am.J. Physiol. 264 (Renal Fluid Electrolyte Physiol. 33): F221-F227,
      1993]. To characterize the specific function regulated by CT, rat CCDs were
      perfused in vitro. Total CO2 net fluxes (JtCO2, pmol.mm-1.min-1) and
      transepithelial voltage (Vt) were measured. Bath CT induced a significant tCO2
      reabsorption. This effect was higher on CCDs harvested from acid-loaded than from
      control rats. When HCO3- secretion was blocked, CT also raised JtCO2 and Vt. When
      H+ secretion was blocked, CT was ineffective on JtCO2 and Vt. When HCO3-
      secretion was increased and H+ secretion was inhibited, CT did not change JtCO2,
      whereas isoproterenol (ISO) increased tCO2 secretion from -13.5 +/- 2.0 (control)
      to -19.0 +/- 2.4 (ISO). In rat CCD studied under these same preceding conditions
      plus luminal amiloride to block the Na(+)-dependent Vt, CT did not alter Vt,
      whereas ISO increased it by 4.5 +/- 0.7 mV. We conclude from these data that, in
      the rat CCD, calcitonin stimulates H+ secretion, likely by so-called alpha
      intercalated (alpha-IC) cells, whereas ISO stimulates HCO3- secretion, likely by
      so-called beta-IC cells.

PMID- 8997397
TI  - Single-channel properties of swelling-activated anion conductance in rat inner
      medullary collecting duct cells.
AB  - Single-channel properties of the volume-activated outwardly rectifying Cl-
      conductance of rat IMCD cells were studied in primary cultures by means of the
      patch-clamp technique in the whole cell and in the outside-out configuration.
      Measurements were performed by noise analysis and in single-channel recordings
      during voltage-induced current inactivation and reactivation and in long-lasting
      experiments at constant membrane voltages. Unitary conductances could be defined
      for the voltage range of -100 to -50 mV and between +50 and +120 mV and chord
      conductances of 34.1 and 76.6 pS, respectively, can be calculated. The overall
      current-to-voltage relationship very much resembles that of the macroscopic Cl-
      conductance and the open probability of the activated channel is close to unity
      (Po = 0.98-0.99). The channel exhibits many similarities to volume-activated
      outwardly rectifying Cl- channels found in other systems although certain species
      differences do exist.

PMID- 8997398
TI  - NaCl but not urea activates p38 and jun kinase in mIMCD3 murine inner medullary
      cells.
AB  - The mitogen-activated protein kinases (MAPKs), p38 and jun kinase (JNK), are
      activated by diverse stressors in cells of nonrenal medullary origin. Epithelial
      cells of the renal medulla are among the very few cells of higher eukaryotes
      routinely subjected to hyperosmotic stress, composed of principally NaCl and
      urea. Hyperosmotic NaCl activated p38 and JNK in a time- and dose-dependent
      fashion in cells of the murine terminal inner medullary collecting duct cell line
      (mIMCD3) as determined by immune complex kinase assay. Hyperosmotic urea exerted
      a minimal effect upon only p38 activation, which was evident only at 5 min. The
      NaCl effect was dose dependent to 800 mosmol/kgH2O; 800 mosmol/kgH2O urea, in
      contrast, exerted no effect. Consistent with these observations, NaCl (800
      mosmol/kgH2O) but not urea (800 mosmol/kgH2O) increased tyrosine phosphorylation
      of p38 and JNK at 10 min. Therefore, even in the extremely osmotolerant renal
      medullary mIMCD3 cell line, derived from a tissue adapted for routine exposure to
      elevated osmolality, hypertonic NaCl activated two stress-responsive MAPKs. Urea,
      in contrast, exerted virtually no effect; therefore, cellular protection from
      urea stress operates through a mechanism distinct from the stress-responsive
      MAPKs.

PMID- 8997399
TI  - Angiotensin II-receptor stimulation of cytosolic calcium concentration in
      cultured renal resistance arterioles.
AB  - This study provides an initial characterization of basic morphological properties
      of cultures of vascular smooth muscle cells (VSMC) from rat preglomerular
      resistance vessels and of the functional coupling of angiotensin II (ANG II)
      receptors to cytosolic free calcium concentration ([Ca2+]i (fura 2 fluorescence
      photometry). Renal VSMC were isolated from interlobular arteries and afferent
      arterioles (< 50 microns) using an iron oxide sieving method and compared with
      rat aortic VSMC cultured under similar conditions. Quiescent monolayers
      maintained uniform morphology and [Ca2+]i signaling profile between passages 3
      and 10. Arteriolar and aortic VSMC were spindle shaped and expressed smooth
      muscle-specific alpha-actin and myosin heavy chains SM-1 and SM-2. ANG II caused
      a rapid increase in [Ca2+]i, followed by a sustained plateau phase at 50-60% of
      the peak value. The initial maximum [Ca2+]i responses were dose dependent and of
      similar magnitude in renal arteriolar and aortic VSMC. ANG II (10(-7) M)
      increased [Ca2+]i from 50 to 240 nM in arteriolar and from 57 to 201 nM in aortic
      VSMC (P < 0.001 for both). Inhibition of ANG II effects on [Ca2+]i revealed
      significant signaling through distinct AT-receptor subtypes (losartan and PD
      123319 sensitive) in renal arteriolar VSMC. In contrast, only losartan was
      effective in aortic VSMC. The AT2-receptor ligand CGP-42112 had no effect in
      either vessel type. Our results demonstrate that cultured arteriolar VSMC have
      anatomical similarities to aortic VSMC and functional differences in AT-receptor
      signaling in response to ANG II. This novel preparation should provide a useful
      approach with which to investigate cellular mechanisms concerning receptor
      coupling to signaling pathways involved in vascular reactivity of arteriolar VSMC
      in the microcirculation in general and the kidney in particular.

PMID- 8997400
TI  - Hyperosmolality inhibits sodium absorption and chloride secretion in mIMCD-K2
      cells.
AB  - Previously we demonstrated that a cell line derived from mouse inner medullary
      collecting duct (mIMCD-K2) absorbs Na+ and secretes Cl- by electrogenic
      mechanisms and that arginine vasopressin (AVP) stimulates Cl- secretion. The
      objective of the present study was to determine whether hyperosmolality, both
      acute (minutes) and chronic (weeks), affects electrogenic Na+ absorption IscNa
      and electrogenic Cl- secretion IscCl across the IMCD. To this end, we measured
      IscNa and IscCl across monolayers of mIMCD-K2 cells mounted in Ussing-type
      chambers. Osmolality was increased from 290 to 590 mosmol/kgH2O by adding 200
      mosmol/kgH2O of NaCl and 100 mosmol/kgH2O of urea or 300 mosmol/kgH2O of sucrose
      to the bathing solutions. Acute and chronic hyperosmolality reduced basal IscNa
      and IscCl and the AVP-stimulated rise in IscCl. These findings indicate that
      osmolality is an important determinant of IscNa and IscCl across IMCD cells and
      that the osmolality of the interstitial fluid should be considered when
      evaluating the effects of hormones and other factors on Na+ and Cl- transport by
      the IMCD.

PMID- 8997401
TI  - Functional differentiation of the human red blood cell and kidney urea
      transporters.
AB  - The recent cloning of two urea transporters will allow to better understand their
      role in the urinary concentrating mechanism. This physiological approach needs to
      be sustained by a knowledge of their functional characteristics. We compared the
      pharmacological properties of the human red blood cell and kidney urea
      transporters (HUT11 and HUT2) in the Xenopus oocyte expression system. Both
      proteins allow the rapid transfer of urea but not of water. Both are inhibited by
      phloretin, although with different half-maximal inhibitory concentrations (IC50;
      75 microM, for HUT11 and 230 microM for HUT2). Whereas para-chloromercuribenzene
      sulfonate inhibits HUT11 with an IC50 of 150 microM, it does not inhibit HUT2,
      whatever the concentration used. We demonstrate that thiourea diffuses through
      HUT11 with a Michaelis constant (Km) of 40 mM, but not through HUT2. In contrast,
      it inhibits urea transport through both proteins. This identification of a
      substrate binding site independent from the transport activity is the first step
      in the understanding of the molecular events underlying urea transport.

PMID- 8997403
TI  - Introduction to medical physiology: cellular membranes and transmembrane
      transport of solutes and water.
AB  - This article summarizes the comments made in the introductory session of the
      Medical Physiology course taught at the University of Alabama School of Medicine.
      The main thesis is that learning physiology is easier when fundamental principles
      are first delineated. Four general principles of physiology (mass balance, force
      flow, capacitance, and equilibrium) are discussed. Clinical medicine becomes more
      comprehensible when these basic principles are understood. Cellular Physiology is
      taught first because it forms the conceptual basis for what follows in the
      course. The idea that the root of clinical medicine lies in the basic sciences is
      emphasized.

PMID- 8997402
TI  - NaCl and/or urea infusion fails to increase renal inner medullary myo-inositol in
      protein-deprived rats.
AB  - As we recently demonstrated that in potassium depletion a decrease in inner
      medullary organic osmolytes might precede and cause a renal concentrating defect,
      we hypothesized that in the protein deprivation the same mechanism may occur. To
      clarify the relationship between renal medullary organic osmolytes and urine
      concentration defects during protein deprivation, we examined the effect of
      protein malnutrition on organic osmolyte content after water deprivation or
      sodium and/or urea infusion. Water deprivation did not restore urine urea and
      osmolality or tissue sodium and urea in protein-deprived rats to control levels.
      NaCl infusion only increased urinary and medullary Na. Urea infusion increased
      medullary urea but not urine urea. NaCl plus urea infusion increased only urinary
      sodium and urea. Regardless of the protocols of hyperosmolality used, protein
      deprivation significantly decreased the medullary contents of myo-inositol and
      taurine and the level of sodium-dependent myo-inositol transporter mRNA. We
      conclude that factors other than NaCl and urea but associated with protein
      feeding are responsible for the decreased accumulation of organic osmolytes.

PMID- 8997404
TI  - Professional development: a guide to the educator's portfolio.
AB  - The educator's portfolio provides a mechanism for identifying and evaluating
      faculty teaching activities. The educator's portfolio has separate areas for
      educational research, teaching encounters, and educational service. This article
      describes the components of a traditional educator's portfolio and relates them
      to the basic scientist's curriculum vitae. The article concludes with suggestions
      for implementing use of the educator's portfolio at the departmental and
      institutional level.

PMID- 8997405
TI  - Construction of a model demonstrating neural pathways and reflex arcs.
AB  - Employment opportunities in the future will require higher skills and an
      understanding of mathematics and science. As a result of the growing number of
      careers that require solid science and mathematics training, the methods of
      science education are undergoing major reform. To adequately equip students for
      technologically advanced positions, new teaching methods must be developed that
      prepare tomorrow's workforce for the challenges of the 21st century. One such
      method is the use of models. By actively building and manipulating concrete
      models that represent scientific concepts, students are involved in the most
      basic level of Piaget's learning scheme: the sensorimotor stage. Models are
      useful in reaching all students at the foundational levels of learning, and
      further learning experiences are rapidly moved through higher learning levels.
      This success ensures greater comprehension and understanding compared with the
      traditional methods of rote memorization. We developed an exercise for the
      construction of an inexpensive, easy-to-build model demonstrating neural pathways
      and reflex arcs. Our exercise also includes many supplemental teaching tools. The
      exercise is designed to fulfill the need of sound physiological teaching
      materials for high school students.

PMID- 8997406
TI  - How many pounds of oxygen do we "eat" each day?
AB  - As teachers we feel the need to do more than merely teach basic facts and
      concepts. We want to make the subject matter more relevant; we would like to help
      integrate the various threads of the students' education and life experiences;
      and, finally, we wish to increase the students' interest and involvement in the
      learning process. There is the temptation, however, when thinking along these
      lines, to consider the use of time-consuming, complex methods of approach. These
      might involve slide presentations, videos, special lectures, special assignments,
      student, reports, etc: The very complexity of these approaches often reduces
      their effectiveness. Moreover, the time and effort required often keeps us from
      attempting them more than once or twice. Are simpler and more effective
      approaches to enrichment possible? Reflecting on our own education, many of us
      may recall the disproportionate impact of some revealing aside thrown by a
      teacher unexpectedly into an otherwise mundane lecture or discussion: perhaps a
      short, penetrating observation providing an unexpected perspective on what was
      being discussed, a bolt of lightening that briefly illuminated the dim landscape
      of the classroom. This we may remember when much from the course has been totally
      forgotten. These jewels of thought--epiphanies--can be shared by teachers to
      enrich, enlighten, and refresh their students and each other. The jewels we speak
      of need not be precious or rare. Indeed, the metaphors "a bolt of lightening" and
      "jewels" may mislead by their intensity and drama. Is it not in the often
      unexamined, simple, and humble all around us that wisdom can be found? The
      following is an example.

PMID- 8997407
TI  - Debate: a tool for teaching graduate students.
AB  - The introduction of a formal debate was used to stimulate discussion of
      neuroscience in our graduate program. The debate had several advantages for
      encouraging student participation. Several students actively participated in the
      debate: four debaters and five judges. Faculty coaches helped provide background
      knowledge and guidance before the debate but were not debaters. Faculty directed
      the judges in methods of evaluation but were not judges. It was felt that this
      method of teaching was not only fun, but also provided an opportunity to learn
      current topics in neuroscience, method of presentation, and critical evaluation.

PMID- 8997408
TI  - Cooperative quizzes in the anatomy and physiology laboratory: a description and
      evaluation.
AB  - Physiology educators read journals, such as this one, to gather ideas about
      curriculum and instruction. Most articles focus on curriculum (i.e., what is
      taught), but this paper will focus on instruction (i.e., how curriculum is
      implemented). Just as there are different types of curricula, there are different
      types of instruction. The most common strategy is lecture. Lectures are extremely
      efficient for delivering large amounts of information in a short period of time.
      A common laboratory strategy is discovery or inquiry-based learning (i.e., giving
      students tools, cognitive and physical, to deduce new information via
      investigations). A third instructional strategy is the use of cooperative
      learning. Proper conditions are required for each instructional strategy, and
      problems arise when the wrong combinations are put together. This paper will
      describe how a cooperative learning environment can be created in the anatomy and
      physiology laboratory through the use of cooperative quizzes. It will include a
      brief introduction to the pedagogical theory behind cooperative learning and an
      evaluation of the effectiveness of quizzes compared with more traditional
      methods.

PMID- 8997409
TI  - A comparison of methods for dealing with troublesome examination questions.
AB  - This study compared two methods for identifying troublesome examination
      questions: a postexam student "challenge committee" process and a "question
      citation" procedure allowing students to identify troublesome questions during an
      exam. Challenged and cited questions on eight examinations given to second-year
      medical students were compared with respect to the percentage of correct
      responses (%CR) and the discrimination index (DI). Challenged questions had a
      significantly lower mean value for %CR (53.2 +/- 22.5, n = 74) than unchallenged
      questions (84.7 +/- 15.4, n = 428) but the two groups did not differ with respect
      to DI. For cited questions, the number of citations was correlated with %CR (r = 
      0.5480, p < 0.001) but not with DI. The group of questions that received three or
      more citations (n = 145) included 67.6% of all challenged questions and 78.3% of
      challenges that eventually led to a change in an answer key. A simple citation
      procedure completed during an exam could replace a complicated, post-exam
      challenge committee process and achieve the same goal of identifying troublesome
      questions.

PMID- 8997410
TI  - Using situational physiology in a didactic lecture setting.
AB  - This project used the approach of "human situations" to teach about the
      cardiovascular system within an undergraduate physiology course (PGY 412). About
      two-thirds of the students had previously taken a college-level physiology course
      (sophisticated), whereas one-third had not (naive). Nine didactic lectures were
      organized around the common human situations of orthostasis, blood donation, and
      exercise. For acceptance evaluation, the students were given a questionnaire
      consisting of six expectation statements (e.g., compared with other life science
      courses, I expect that I will better understand the material) and asked to rate
      the degree to which they agreed with each statement on a scale of 1 to 5. On
      completion of the lectures, the students were given a questionnaire asking them
      to compare experiences with expectations. Experiences were significantly less
      than expectations for naive (P < 0.05) but not for sophisticated students. On a
      scale of 1 to 5, sophisticated students preferred the situations approach more
      than did naive students (3.1 vs 2.4; P < 0.066). For performance evaluation, the
      students were given a set of questions used by the author in a previous PGY 412
      course presented by traditional didactic lectures. There were no significant
      differences between present and previous scores (77 vs. 79%; P > 0.16).
      Furthermore, there were no significant differences between naive and
      sophisticated students in cardiovascular examination scores (P > 0.608) or in
      total course scores (P > 0.523). These results indicate that didactic lectures
      based on situational physiology will yield a performance outcome equivalent to
      traditional lectures. However, naive students may have difficulty with the
      procedure and require extra attention.

PMID- 8997411
TI  - It's time for a change in the way we educate physiology PhD candidates.
AB  - Graduate students in physiology programs today are faced with a job market that
      is significantly different from that which many of us faced 25, 10, or even 5
      years ago. As a result, physiology educators need to change the content and style
      of their programs to prepare graduates for their futures. Programs must continue
      to prepare graduates for research postdoctoral positions, but they also should
      prepare them for employment at smaller institutions that have higher teaching
      demands and that encourage, but do not require, research. Changes are suggested
      in the way PhD candidates are taught and in the way professors mentor students
      seeking employment at smaller institutions.

PMID- 8997412
TI  - Physiology research in the developing world.

PMID- 8997413
TI  - Dementia: diagnostics, early treatment, and assistance from family members.
AB  - This state of the art document is the result of the conference held in Stockholm
      on March 9-10, 1995, initiated by the Swedish Medical Research Council. The
      conference brought together researchers from basic science and clinic to
      different disciplines. Response to questions was given in small groups and the
      answers were presented and discussed with all the participants. The final
      consensus was formulated in this larger group and comprises the state of the art
      document.

PMID- 8997414
TI  - What is dementia?
AB  - Dementia is a descriptive term derived from the Latin root de mens, indicating an
      observable decline in mental abilities. It is an acquired clinical syndrome
      characterised by deterioration of mental functioning in its cognitive, emotional
      and conative aspects. The concept is comprehensive with several different
      clinical profiles and courses. The diagnosis of dementia implies that several
      mental faculties are involved and exclude isolated neuropsychiatric disturbances
      such as amnesia and aphasia which occur with focal brain lesions. Description and
      classification of dementia conditions have however to deal with the problem that
      the word "dementia" might have different meanings in different contexts. It might
      denote a clinical syndrome irrespective of etiology, but also imply that the
      etiology of this syndrome is brain dysfunction. Moreover, the term dementia is
      sometimes used in a wider sense to describe the underlying brain disease from its
      early subtle manifestations to advanced stages of severe deterioration. By
      definition this deterioration previously was progressive and irreversible with
      little hope for the patient. Clinical experience however has changed our views,
      and it is now accepted that the course of dementia can be progressive, static or
      remittent.

PMID- 8997415
TI  - Genetics of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterised neuropathologically by the accumulation
      of neuritic plaques and neurofibrillary tangles as well as by cerebrovascular
      amyloid deposition and neuronal cell loss. The major component of neuritic
      plaques and cerebrovascular amyloid is a 40-42 amino acid peptide termed beta
      amyloid, derived as a proteolytic fragment from the large amyloid precursor
      protein (APP), a membrane-bound protein expressed in most tissues. The last few
      years have seen considerable advances in understanding the pathogenesis of
      Alzheimer's disease through genetic studies. The importance of the beta-amyloid
      peptide in the pathogenesis of AD has been strengthened by the identification of
      pathogenic mutations in the APP gene on chromosome 21.

PMID- 8997416
TI  - Frontal lobe degeneration of non-Alzheimer type. Structural characteristics,
      diagnostic criteria and relation to other frontotemporal dementias.
AB  - Frontal lobe degenerative dementias, the second largest degenerative dementia
      group after Alzheimer's disease, is dominated by frontal lobe degeneration of non
      Alzheimer type. It is classified in a group also containing Pick's disease,
      progressive aphasia and dementia in motor neuron disease. Frontal lobe
      degeneration of non-Alzheimer type is clinically marked by frontal lobe symptoms
      and frontotemporal reduction of blood flow. From a histopathological point of
      view it is characterized by gliosis, microvacuolation, neuronal atrophy-loss and
      40-50% loss of synapses in three superficial cortical laminae of the frontal
      convexity and anterior temporal cortex, while the deeper laminae are little or
      not changed. The structural changes of Alzheimer's disease including amyloid,
      Levy body dementia and Pick's disease are entirely lacking. A strong heredity
      points to a genetic cause as yet undefined.

PMID- 8997417
TI  - Fundamental pathological lesions in vascular dementia.
AB  - This review concerns the fundamental cerebral lesions in cases of vascular
      dementia. Extracerebral vascular alterations are dominated by atherosclerosis
      with or without thrombosis. In addition, occlusion of extracerebral arteries can
      be induced by thrombo-embolism and in rare cases by other vascular diseases,
      chiefly arteritis. Intracerebral microangiopathies are usually of
      arteriolosclerotic or hyalinotic types in which there is degeneration of smooth
      muscle cells of the media and deposition of components of extracellular matrix,
      chiefly collagens. Ageing, chronic hypertension, hyperlipidemias and diabetes are
      important factors inducing vascular lesions. The vascular lesions, often combined
      with systemic factors, may produce various ischemic and edematous alterations of
      the brain parenchyma. Occlusion and obliteration of arteries (macroangiopathy)
      are associated with large infarcts, whereas microangiopathy may cause lacunar
      infarcts and some forms of white matter degeneration. Cases of vascular dementia
      usually present many types of lesions in the brain parenchyma and its arterial
      supply. The extent and location of the injuries differ considerably from case to
      case. Location of the lesions, volume of destroyed tissue, multiplicity and
      bilateral occurrence are most important parameters underlying the clinical
      manifestations in vascular dementia. A strategic location of a small injury is in
      some cases of particular importance.

PMID- 8997418
TI  - Current definition and classification of dementia diseases.
AB  - INTRODUCTION: Current clinical diagnosis of dementia diseases mostly relies
      exclusively on the symptom picture, but there is no clear dividing line between
      the symptoms per se and the pathological changes. DISCUSSION: The above
      indistinctness characterizes the current most widely used definitions and
      classification systems for dementia diseases. There is also a lack of
      integration, as different categories of doctors conceptualize the dementia
      syndrome differently, and the various existing classification systems put the
      emphasis on different aspects of dementia diseases. CONCLUSION: As a first step
      towards an up-to-date classification of dementia diseases, a distinction between
      symptoms and pathological changes should be made. A second step is to find
      patterns both of biological markers and of neuropsychiatric symptoms that are
      linked to the various pathological changes of the disease.

PMID- 8997420
TI  - Magnetic resonance imaging and computed tomography in Alzheimer's disease.
AB  - Modern imaging techniques such as X-ray computed tomography (CT) and magnetic
      resonance imaging (MRI) are widely used in the clinical evaluation of patients
      with dementia disorders. Computed tomography was introduced for clinical practice
      in the beginning of the 1970s. The advent of MRI came later with the first
      equipment used for clinical purposes being introduced in the first half of the
      1980s. The two modalities differ in many aspects: CT has a lower contrast
      resolution compared with MRI and is also faster and often more convenient for
      patients. In contrast, MRI gives a superior picture of the brain tissue without
      the use of contrast agents. Moreover, MRI, like CT, does not suffer from bone
      artifacts. The latter is of special importance in the study of dementia diseases
      (especially Alzheimer's) where structural changes are present close to the brain.
      The possibility of image in arbitrary imaging planes also makes MRI more suitable
      to study structures of relevance in Alzheimer's disease such as the medial
      temporal lobes and the hippocampal formation.

PMID- 8997419
TI  - Neuropsychological assessment of dementia: state of the art.
AB  - A comprehensive neuropsychological examination includes an assessment of both
      cognitive functions and personality characteristics. In order to evaluate
      dementia, the patient's present as well as the premorbid functioning has to be
      assessed, which is performed by means of tests, behavioral observations, rating
      scales, and inquiries. These methods are used for diagnostic purposes, for
      differential diagnostics, follow-up studies, and for evaluation of treatment
      effects. Recent research has shown that neuropsychological methods have a high
      sensitivity and specificity in detection of dementia, utilizing measures of
      episodic memory. For staging of dementia, episodic memory as well as other
      cognitive functions are necessary. The effectiveness of dementia differentiation
      by means of neuropsychological methods varies from quite good regarding frontal
      lobe degeneration to less good regarding cerebrovascular dementias, probably due
      to the variation in site, extent, number, and temporal characteristics of the
      lesion. Future development is required regarding methods for evaluation of
      premorbid functioning, instruments for assessment of executive functions, and
      personality characteristics in dementia. Furthermore, brain-behavior studies are
      needed to learn more about the relation between neuropsychological measures vs
      neuropathology, neurochemistry, and neuroimaging.

PMID- 8997421
TI  - SPECT measurements of brain function in dementia; a review.
AB  - A brief review of the role of SPECT (single photon emission computed tomography)
      in the diagnosis of dementing brain disease is given. Between 1990 and 1995 some
      100 original articles deal with SPECT measurements with radioactive tracers of
      brain function in demented patients. The main field is measurement of regional
      cerebral blood flow (rCBF) but there is an increasing number of studies
      concerning receptor functions in the demented brain.

PMID- 8997422
TI  - Diagnosis of dementia by regional cerebral blood flow measurements using 133Xe
      and stationary detectors.

PMID- 8997423
TI  - Electroencephalography as a diagnostic tool in dementia; a review.

PMID- 8997424
TI  - Application of PET in dementia disorders.
AB  - Positron emission tomography (PET) is a valuable tool for understanding of
      functional correlates of biological and structural changes in brain of patients
      with various dementia diseases. As such it can provide valuable physiological
      correlates important for diagnosis, management and research of dementia
      disorders. A crucial question is whether PET is capable of early or preclinical
      detection of dementia. Longitudinal PET studies in Alzheimer families with
      chromosomal aberrations will be important for. Impairment of cerebral blood flow
      and glucose metabolism is a common feature in patients with Alzheimer's disease.
      The pattern of changes is distinct from other forms of dementia and correlates
      with neuropsychological impairments. Neuroreceptor studies have to be further
      applied as well as monitoring of drug treatment effects.

PMID- 8997425
TI  - The neurochemistry of Alzheimer's disease.
AB  - The last 15-20 years have seen a wealth of studies to characterize the
      neurochemical abnormalities of Alzheimer's disease, in particular those involving
      the beta-amyloid and tau proteins, as well as more recently, apolipoprotein E4.
      This article provides a summary of the evidence for the involvement of these
      proteins in Alzheimer's disease pathogenesis based on postmortem brain and CSF
      studies.

PMID- 8997426
TI  - Pharmacological treatment of cognitive dysfunction in dementia disorders.
AB  - Dementia represents a complex heterogeneity of disorders. For Alzheimer's disease
      great progress in the understanding of underlying genetical, neuropathological
      and neurochemical mechanisms of the disease has been made during recent years. A
      variety of therapeutic approaches with cognitive enhancing drugs have been tested
      in Alzheimer patients. Presently, four main treatment strategies prevail, namely
      transmitter replacement therapy, growth factors, anti-inflammatory drugs and
      drugs affecting amyloid processing in the brain. The transmitter therapy is so
      far the most explored and fruitful strategy. The cholinesterase inhibitor tacrine
      is in clinical use in many countries. Other cholinergic treatment strategies than
      cholinesterase inhibitors in development are selective muscarinic receptor
      agonists and nicotine receptor agonists. The selective 5HT re-uptake blockers
      might be complementary to drugs with more specific effect on cognition. Although
      treatment with growth factor therapy e.g. nerve growth factor in Alzheimer
      patients has given some promising results, further research is needed.
      Development of drugs affecting amyloid processing is still mainly on a
      preclinical level.

PMID- 8997427
TI  - Treatment of non-cognitive symptoms in dementia.
AB  - Non-cognitive symptoms are common in dementia. Emotional disturbances such as
      depression, anxiety and irritability-aggressiveness dominate. Depression is seen
      in about one third of demented persons. There are findings indicating that
      degenerative changes in the brain can cause depressive changes. Depression in
      elderly and in dementia differs from that in younger ages but no diagnostic
      criteria have yet been evaluated. Anxiety is a common symptom in depression
      suggesting a depressive-anxiety disorder. Specific serotonin re-uptake inhibitors
      (SSRI) are efficient in the treatment of both depression and anxiety while
      tricyclic antidepressants have side effects including cognitive reduction.
      Irritability and aggressiveness respond to the treatment with SSRI drugs. Such
      drugs as benzodiazepines and antipsychotics, especially those with
      anticholinergic effects, can reduce cognitive function in elderly and demented
      persons but the knowledge, this side effect is insufficient. Antipsychotics
      without anticholinergic effects should be used for the treatment of psychotic
      symptoms in demented persons.

PMID- 8997428
TI  - Characteristics of the demented living in different settings in Sweden.
AB  - INTRODUCTION: The aim of this paper is to describe elderly people living in
      different care settings in Sweden according to prevalence of dementia, ADL
      functions, psychiatric symptoms, behavioural symptoms and workload imposed on the
      staff. MATERIAL & METHODS: In total 842 persons living in different settings
      (nursing homes, homes for the aged, service houses and group-livings) has been
      investigated. The MDDAS scale has been used to measure motor functions, vision,
      hearing, speech, ADL functions, behavioural disturbances, psychiatric symptoms
      and workload imposed on the staff. RESULTS: Probands cared for in different
      settings differ considerably as to prevalence of dementia, ADL functions,
      behaviour and psychiatric symptoms. Those living in nursing homes were most
      impaired and imposed the heaviest workload on the staff. The study has also shown
      that the nursing load is increasing rapidly in the homes for the aged.

PMID- 8997429
TI  - What are the costs to society and to individuals regarding diagnostic procedures
      and care of patients with dementia?

PMID- 8997430
TI  - Longitudinal course of symptoms of craniomandibular disorders in men and women. A
      10-year follow-up study of an epidemiologic sample.
AB  - An epidemiologic sample (n = 285) drawn from the population of Skelleftea,
      Sweden, was examined to evaluate the prevalence of signs and symptoms of
      craniomandibular disorders (CMD) at the age of 17 years. The sample was then
      followed up prospectively at the ages of 18 and 19 years. The year they reached
      28 years of age a questionnaire concerning prevalence, incidence, frequency,
      duration, location, and intensity of symptoms of CMD was sent to the same
      subjects. Two hundred and thirty-four subjects responded (82%). The number of
      subjects who participated in all examinations (at the ages of 17, 18, 19, and 28
      years) was 215 (107 women and 108 men). During the 10-year period from the late
      teens onwards a significant increase in reported symptoms of CMD occurred in both
      men and women. For the whole sample the prevalence increased from approximately
      20% to 37%. The incidence of CMD symptoms at the age of 28 years was 6% in both
      sexes. Although fluctuations of symptoms during the period from the age of 17 to
      28 occurred in both sexes, the course of CMD in men and women differed
      significantly. All women who consistently reported symptoms at the age of 17-19
      years also reported symptoms at the age of 28 years; the corresponding figure for
      men was 60%. At the age of 17 years 25 women reported CMD; 23 of these reported
      CMD at the age of 28 years (92%). At the age of 17 years 17 men reported CMD; 5
      of these reported CMD at the age of 28 (29%). The result indicates different
      courses for CMD in men and women.

PMID- 8997431
TI  - Variability in fluoride content of subsurface water reservoirs.
AB  - Groundwater may contain high concentrations of fluoride. In most countries,
      however, information on the fluoride content is scarce and anecdotal. The aim of
      the present study was to make a comprehensive assessment of F- in the groundwater
      of a representative area of Norway, thereby establishing a more solid basis for
      appropriate health counseling. Relevant technical information was collected,
      together with water samples from 1063 underground water sources in 31
      municipalities in the county of Hordaland. One thousand and two water samples
      were analyzed for F- and pH with an F(-)-selective electrode and a pH electrode,
      respectively. Mean F- was 0.30 mg/l (range, < 0.02-9.48). Fourteen per cent of
      the wells contained water with F- levels > or = 0.50 mg/l. In three
      municipalities well water had a mean F- concentration > 0.07 mg/l; in one
      instance the mean was as high as 1.45 mg/l. In 10 municipalities maximum F-
      values were > 1.50 mg/l. F- values showed a positive correlation with the pH of
      the water and the depth of the wells (P < 0.01) and a negative correlation with
      the age of the well (P < 0.05). The results indicated that low-capacity wells
      deliver water with a higher F- value than high-capacity wells. This trend,
      however, was not statistically significant. The results show that high-F
      groundwater is prevalent and emphasize that information on domestic water supply
      must be available before supplementary fluoride is prescribed for caries
      prophylactic purpose.

PMID- 8997432
TI  - Judgement of removal of asymptomatic mandibular third molars: influence of
      position, degree of impaction, and patient's age.
AB  - Our aim was to study general dental practitioners' (GDPs') and oral surgeons'
      judgement of the need for removal of asymptomatic mandibular third molars,
      described by three cues. The judges were also asked to estimate the development
      of pathologic conditions. There was considerable variance with regard to the
      individual judgements. As a group, GDPs estimated the need for removal to be
      higher for patients less than 40 years than those more than 40 years old. The
      oral surgeons estimated the need to differ for three different age groups. The
      GDPs estimated the need to be highest for distoangular molars and lowest for
      vertical molars, whereas the oral surgeons estimated these positions to be equal.
      Molars partially covered by soft tissue were given the highest priority for
      removal by both groups of judges. The mean proportion of variation explained by
      the three cues was high, except for tumor development, indicating that the judges
      used the cues and the combination of them to a great extent in their judgement of
      the risk for development of pathologic conditions.

PMID- 8997434
TI  - Oral conditions related to use of the lip plug (ndonya) among the Makonde tribe
      in Tanzania.
AB  - A series of cases of use of lip plugs (ndonya) are reported for members of the
      Makonde tribe living in southern and eastern Tanzania, and examples of damaged
      caused by this custom to the oral and dental structures are described.

PMID- 8997433
TI  - Children's dental health in Europe. Caries treatment need in 5- and 12-year-old
      children from eight EU countries.
AB  - The purpose of this study was to develop methods to evaluate treatment needs
      (TNEED) and previous treatment (TDONE) in different populations. In the
      collaborative study, 'Children's Dental Health in Europe', the methods were used
      in connection with a clinical examination to document and compare treatment needs
      in 200 5-year-olds and 200 12-year-olds from each of the 8 participating
      countries. The study comprised a total of 3200 children from Belgium, Germany,
      Greece, Ireland, Italy, Scotland, Spain, and Sweden. The method for calculating
      TNEED was validated by estimation of required time to meet the treatment needs
      (TNTIME). The calculated TNEED shows a clear relationship with the evaluated
      TNTIME, and the method is applicable to different population subgroups. The
      results revealed large differences in both TNEED and TDONE among the different
      countries and between the two age groups.

PMID- 8997435
TI  - Occurrence of the Carabelli trait in twins discordant or concordant for cleft lip
      and/or palate.
AB  - The frequency and expression of the Carabelli trait among 36 twin pairs
      discordant or concordant for cleft lip and/or palate were investigated. Four of
      10 monozygotic (MZ) and 24 of 26 dizygotic (DZ) pairs of twins were discordant
      for clefts. The frequency of the trait on the first upper molars of the noncleft
      subjects was 79%. It varied from 54% to 61% in the subjects with clefts, and the
      frequency of the trait decreased with increasing extension of the cleft. The
      occurrence of the trait was bilateral in more than 90% of the MZ and the DZ
      subjects. MZ twins had a higher concordance rate for the corresponding molar
      comparisons and for cross-twin comparisons than did the DZ pairs. The
      corresponding polychoric correlations for MZ twin pairs were estimated to be 1.0,
      and for the DZ twin pairs estimates ranged from 0.4 to 0.5. Thus, genetic factors
      appear to control the Carabelli trait, and the heritability seems to be high even
      in our cleft lip and/or palate twins.

PMID- 8997436
TI  - Dental erosion, soft-drink intake, and oral health in young Saudi men, and the
      development of a system for assessing erosive anterior tooth wear.
AB  - The aim of the study was to investigate some aspects of the oral health of male
      Saudi military inductees with special reference to soft-drink consumption, dental
      erosion, caries and fluorosis prevalences; a second aim of the study was to
      develop a system for assessing dental erosion. The material comprised a random
      selection of 95 individuals with a mean age of 20.9 years (range, 19-25 years). A
      questionnaire survey was made of each individual's dietary and oral hygiene
      habits and general and oral health, in addition to clinical, study cast,
      radiographic, and photographic examinations. The results showed that soft-drink
      consumption in the sample (x = 247 1/year) far exceeded that found in Western
      populations and that professional and self-administered dental care were
      generally scant. Twenty-eight percent of the maxillary anterior teeth showed
      pronounced dental erosion. Fluorosis was a common finding, and the number of
      untreated carious cavities was high. DMFT (mean = 10.0; DT = 7.7; MT = 0.5; FT =
      1.8) and DMFS (mean = 18.3; DS = 12.6; MS = 2.5; FS = 3.2) were higher than those
      of comparable Western populations and showed an approximately threefold increase
      over a period of about 18 years as compared with that previously reported in a
      similar Saudi sample. In view of the high frequencies of dental erosion,
      untreated carious cavities, and fluorosis reported here and the strong indication
      of an increasing caries prevalence, the need for serious recognition of the
      implications in the planning of future dental health care program is stressed.

PMID- 8997437
TI  - Height of mandibular basal bone in dentate and edentulous subjects.
AB  - Age-related differences in the height of the mandibular basal bone were compared
      between young and old dentate subjects and between dentate and old edentulous
      subjects by means of panoramic radiographs. The distances of the mental foramen
      and mandibular canal from the lower border of the mandible, when measured, showed
      the mandibular basal bones in old dentate and in old edentulous men to be higher
      than those of young dentate men in the molar region (P < 0.05). The height of the
      basal bone below the mental foramen was smaller in old edentulous women than in
      young and old dentate women (P < 0.05). A slight bone deposition along the lower
      border of the mandible in the molar region seems to take place with increasing
      age. The mental foramina of edentulous women move toward the lower border of the
      mandible as a result of alveolar bone resorption.

PMID- 8997438
TI  - Association between radiographic findings in the mandibular condyle and
      temporomandibular dysfunction in an elderly population.
AB  - Our aims were to study the prevalence of abnormal radiographic findings in
      mandibular condyles and the possible association between such findings and
      clinical signs and symptoms of temporomandibular dysfunction (TMD) and dental
      state. Two cohorts of 70-year-old people, 384 men and 484 women, living in
      Goteborg, Sweden, participated in the study. The first cohort was examined in
      1972 and the other one in 1992. Besides a functional and clinical examination, a
      questionnaire on TMD and panoramic radiography were included. A deviation from
      the normal appearance of one or both condyles was found in 26% of the subjects
      (17% of the condyles). There was no significant difference in this respect
      between the two cohorts. There were in general only minor and no statistically
      significant differences between those with normal and deviating condylar findings
      with regard to various TMD signs and symptoms. The subjects in Eichner group A
      (with dental support in all zones) showed a slightly lower frequency of abnormal
      radiographic condylar findings (22%) than those in groups B (reduced dental
      support) and C (edentulous in one or both jaws; both B and C, 28%). It is
      concluded that abnormal radiographic condylar findings in these elderly people
      were not at all or only weakly correlated with signs and symptoms of TMD and
      dental status.

PMID- 8997440
TI  - Comments on the article 'Metal-ceramic bond strength'.

PMID- 8997441
TI  - The development of nerve connections in the peripheral nervous system.
AB  - The structural basis for the functions of the brain is the wiring of nerve cells.
      The wiring is achieved by 100 billion neurons via some 100,000 billion synaptic
      connections. Formation of this network is a formidable task which requires
      intricate, but also reliable mechanisms at work. It is generally recognized that
      the precise connections between nerve cells are accomplished by two different
      sorts of mechanisms. First, various molecular guidance cues lead outgrowing axons
      from specific areas to particular target regions which are rather broadly
      defined. The second stage includes an exact, point-to-point matching between each
      axon and the specific target neurons. This is achieved by an intricate
      interaction between the involved nerve cells. In the following, the attention
      will primarily regard the second type of events, but some aspects on the initial
      outgrowth of axons and axon guidance mechanisms will also be given. A large part
      of the description will focus on the neuromuscular junction, since it has been
      extensively used as a model for the study of synapse development.

PMID- 8997439
TI  - Effects of oral hygiene products containing lactoperoxidase, lysozyme, and
      lactoferrin on the composition of whole saliva and on subjective oral symptoms in
      patients with xerostomia.
AB  - This study evaluates the effects of two oral hygiene products containing
      nonimmunoglobulin antimicrobial agents on whole saliva and on subjective oral
      symptoms in patients with xerostomia. Twenty patients used a lactoperoxidase
      system-containing toothpaste (Biotene) combined with the use of a mouthrinse
      (Biotene), comprising also lysozyme and lactoferrin, for 4 weeks. Saliva samples
      were collected at base line, after 4 weeks' use of the products, and at the end
      of a 4-week washout period. Samples were analyzed for selected biochemical and
      microbiologic factors. The effects on subjective oral symptoms were also
      recorded. A 4-week daily use of toothpaste and mouthrinse relieved the symptoms
      of oral dryness in 16 patients. The levels of salivary hypothiocyanite, lysozyme,
      lactoferrin, or myeloperoxidase activity did not change, but there was a
      significant decrease in salivary pH (P < 0.05), total peroxidase activity (P <
      0.05), and total protein content (P = 0.01). In patients with the lowest salivary
      flow rates (n = 5) a significant (P > or = 0.04) increase was detected in
      salivary hypothiocyanite concentrations. No major changes occurred in salivary
      microflora. The products relieved subjective oral symptoms in most xerostomic
      patients, but this was not necessarily related to the presence of antimicrobial
      agents.

PMID- 8997442
TI  - Perinatal stimulation and adaptation of the neonate.
AB  - The present report describes psychobiological studies of behavior around the time
      of birth. An adaptive, ecological perspective is presented in which stimulation
      of the fetus and newborn is purported to instigate adaptive postpartum behavior.
      Studies describing the perinatal sensory environment are reviewed, with a
      consideration of emergent sensory function of the fetus. It is asserted that
      afferent input associated with parturition perturbs the fetus and neonate,
      producing a general arousal state that facilitates breathing, suckling, and early
      learning. The view developed herein is that perinatal sensory input induces and
      canalizes the newborn's behavior, thereby regulating adaptive postpartum
      function. Deviations in afferent input may alter ontogenetic trajectories and
      compromise developmental outcome by reducing availability of conditions necessary
      for adequate postpartum adaptation.

PMID- 8997443
TI  - Fetal memory: does it exist? What does it do?
AB  - Whether fetal memory exists has attracted interest for many thousands of years.
      The following review draws on recent experimental evidence to consider two
      questions: does the fetus have a memory? And, if so, what function(s) does it
      serve? Evidence from fetal learning paradigms of classical conditioning,
      habituation and exposure learning reveal that the fetus does have a memory. By
      comparison little attention has been paid to the possible function of memory.
      Possible functions discussed are: practice, recognition of and attachment to the
      mother, promotion of breastfeeding, and language acquisition. It is concluded
      that the fetus does possess a memory but that more attention to the functions of
      fetal memory will guide future studies of fetal memory abilities.

PMID- 8997444
TI  - Effectiveness of individualized neurodevelopmental care in the newborn intensive
      care unit (NICU).
AB  - The individual infant's neurodevelopmental process provides an integrative
      framework for the delivery of medical care needed to assure the infant's survival
      and quality of outcome. The infant's neurobehavioral functioning and expression
      provides an opportunity for caregivers to estimate the individual infant's
      current strengths, vulnerabilities and threshold to disorganization, as well as
      to identify the infant's strategies in collaborating in his or her best
      progression. This perspective supports caregivers in seeing themselves in a
      relationship with the infant, and in considering opportunities to enhance the
      infant's strengths and reduce apparent stressors in collaboration with the infant
      and the family. The results of several randomized studies supporting the
      effectiveness of such a neurodevelopment approach to NICU care will be presented,
      and suggest implications for staff education and nursery-wide implementation.

PMID- 8997445
TI  - Does neurological assessment still have a place in the NICU?
AB  - Comments at discharge from the neonatal intensive care unit tend to concern
      porencephalic cysts or ventricular dilatation rather than clinical neurological
      findings. This neglect in collecting clinical information can be understood
      during the acute stage of neonatal adaptation due to the non-specificity and
      lability of many neurological signs. However, it does not seem justified when the
      infant has recovered, can breathe on his/her own and can tolerate handling. To
      define optimal Central Nervous System function at 40 weeks (just born or
      corrected), a simple basic assessment composed of nine variables is proposed,
      with descriptions and illustrations. Rationale for the timing and selection of
      variables is discussed. The benefit of this clinical approach is to subdivide
      children with normal ultrasound imaging into two subgroups according to non
      optimal or optimal responses. Prospective follow-up of children with non-optimal
      responses will reduce the number of late diagnoses of developmental disabilities.
      Rational optimism for the others will diminish parents' anxiety and neurologic
      clinics' overload.

PMID- 8997446
TI  - The assessment of general movements is a valuable technique for the detection of
      brain dysfunction in young infants. A review.
AB  - Recently, a new assessment technique by which to evaluate brain function in the
      fetus and newborn infant has been developed. The method is based on the
      assessment of the quality of General Movements (GMs). GMs are complex movements
      involving all parts of the body. They are present throughout fetal life and
      postnatally until about 3-4 months post-term. The persistent presence of abnormal
      GMs during the neonatal period and the absence of age-specific characteristics
      ("fidgety" movements) around 3 months-post term are both powerful predictors of
      the development of handicap.

PMID- 8997447
TI  - Very preterm infants at fourteen years: relationship with neonatal ultrasound
      brain scans and neurodevelopmental status at one year.
AB  - A follow-up study was carried out on a cohort of 1142 very preterm (< 33 weeks)
      survivors who had ultrasound (US) brain scanning from birth. Follow-up was
      continued into adolescence, and included magnetic resonance imaging (MRI) of the
      brain at 14-15 y. Neonatal US findings and neurodevelopmental status at 1 y
      predicted outcome at 8 and 14 y, including cognitive development, poor
      interhemispheric interaction and school performance. MR brain imaging indicated
      that neonatal US accurately identified serious, permanent lesions in the brains
      of these very preterm infants, although US failed to recognise a large proportion
      of the abnormalities detected in adolescence by MRI. Atrophy of the corpus
      callosum was one of the commonest findings on MRI brain scans, supporting the
      hypothesis that damage to this important commissure may account for the poor
      school performance reported in very low birthweight infants.

PMID- 8997448
TI  - The changing panorama of cerebral palsy--bilateral spastic forms in particular.
AB  - Our Swedish population-based cerebral palsy (CP) project started 25 years ago and
      today covers the birth years 1954-1990, with over 1400 CP cases. This large
      series (1, 2, 3) has opened new perspectives on time trends and aetiological
      background factors, where two areas of successively increasing knowledge stand
      out as particularly helpful. One is the growing amount of biological and clinical
      data from the continuously increasing cohorts of surviving very preterm infants,
      the other is the rapidly expanding and refined information from neuroimaging.
      Bilateral spastic CP (BSCP), including spastic and ataxic diplegia, tetraplegia
      and spastic-dyskinetic CP, is the most prevalent clinical group of CP syndromes,
      present in around 75% of preterm and 45% of term CP, and has shown the most
      significant prevalence changes over time. In this presentation we, therefore,
      focus on BSCP, also analysed in a collaborative study between southwest Germany
      and western Sweden and recently presented in a series of four papers (4, 5, 6,
      7).

PMID- 8997449
TI  - Development and reorganization of descending motor pathways in children with
      hemiplegic cerebral palsy.
AB  - Reorganization of descending motor pathways was explored in 33 subjects with
      hemiplegic cerebral palsy. Subjects were assessed neurologically and surface
      electromyographic recordings were taken from homologous muscles of both hands.
      Functional corticospinal projections were assessed using focal magnetic
      stimulation of the motor cortex. In control subjects this evokes EMG responses in
      the contralateral hand at short latency. Similar results were seen in 12 of the
      hemiplegic subjects following stimulation of the undamaged motor cortex. In the
      remaining 22 subjects novel corticospinal pathways were demonstrated arising from
      the undamaged cortex, where stimulation evoked short latency EMG responses in
      both hands. Cross-correlation analysis performed from EMGs recorded between the
      two hands revealed short duration central peaks in 11 of these subjects, all of
      whom had strong mirror movements of the hands. These findings suggested that two
      patterns of central reorganization may follow early unilateral cortical insult.
      Examination further indicated that hand function in hemiplegic subjects could be
      related to the neurophysiological results.

PMID- 8997450
TI  - Neural and musculoskeletal contributions to the development of stance balance
      control in typical children and in children with cerebral palsy.
AB  - Studies on the development of automatic postural responses in both typically
      developing children and children with cerebral palsy were performed. With the
      appearance of "pull-to-stand" behavior, typically developing children first began
      to show muscle responses to platform movements in mainly the ankle muscles. With
      increased development, additional agonist muscles were added to the response
      pattern and a consistent distal to proximal sequence began to emerge. Well
      organized responses were seen with the onset of independent stance and walking,
      along with the reduction of antagonist muscle co-activation. The older children
      with cerebral palsy who were pre-walkers had immature muscle activation patterns
      like those seen in the typically developing children at the pull-to-stand stage
      of development. These included disorganized muscle responses and increased
      frequency of coactivation of both proximal-distal and agonist-antagonist muscles.
      In order to determine if musculoskeletal constraints contributed to these
      response patterns, normal children were asked to stand in a crouched posture
      similar to that of children with CP. This caused postural muscle response
      patterns to more closely approximate those of children with spastic diplegia.

PMID- 8997451
TI  - Cognitive explanations of autism.
AB  - A brief review of the theory of mind account of autism is presented. A lack of
      theory of mind in autism is well supported by empirical studies and can explain
      quite specifically the nature of the social communication impairments. Other
      characteristic behavioural features of autism, in particular perseveration and
      rigidity, are tackled by the hypothesis of executive function deficits. The
      theory of weak central coherence attempts to explain the uneven pattern of
      intellectual abilities seen in autistic individuals, proposing that they adopt a
      distinctive cognitive style. It is likely that a number of separate cognitive
      deficits will be identified and that these will provide clues to the underlying
      brain abnormalities in autism.

PMID- 8997452
TI  - The oxidation hypothesis of atherosclerosis: an update.
AB  - Hypercholesterolemia is associated with an increased risk of atherosclerosis. The
      oxidation hypothesis suggests that oxidative modification of lipoprotein, and in
      particular low-density lipoprotein (LDL), increases its atherogenicity by
      altering receptor-mediated uptake by cells in the intima of blood vessels.
      Oxidized LDL is taken up by scavenger receptors on monocytes, smooth muscle
      cells, and macrophages in an uncontrolled process leading to accumulation of
      lipid and the formation of foam cells, an early feature of atherosclerotic
      plaque. Recent research on the oxidation of LDL lipids, the effect of
      antioxidants, hypertensives, and other agents, the interaction of LDL with
      extrinsic factors, as well as patient studies which bear on the oxidation
      hypothesis, are summarised in this review.

PMID- 8997454
TI  - Interleukin-6-associated laboratory parameters and immunohistochemistry in
      symptomatic stage A and B nodular sclerosing Hodgkin's disease in children.
AB  - Interleukin (IL)-6-associated laboratory parameters obtained at diagnosis on 17
      children with histologically confirmed nodular sclerosing Hodgkin's disease
      (NSHD) are reported. When these patients were grouped as either symptomatic stage
      A or B, they were found to be similar in extent of disease, age, and gender.
      However, statistically significant differences between these two groups were
      observed for the means of the following IL-6-associated laboratory parameters:
      hematocrit (p = 0.019), platelet count (p = 0.009), serum albumin (p = 0.001),
      and ferritin (p = 0.037) concentrations. Moreover, trend analysis of abnormalcy
      revealed an increasing frequency of anemia, thrombocytosis, hypoalbuminemia, and
      hyperferritinemia between stage A and B patients and, when available, febrile
      controls (p values = 0.0012, 0.0009, 0.0406, and 0.0011, respectively).
      Correspondingly, IL-6 immunohistochemistry performed on archival material from
      representative cases in each group showed greater overall reactivity in specimens
      from stage B patients. A variety of cells accounted for this positivity for IL-6
      antigen including Reed-Sternberg cells and their variants, lacunar cells,
      dendritic interdigitating cells, endothelial cells, fibroblasts, and vascular
      smooth muscle cells. In summary, greater and more frequent abnormalities in IL-6
      associated laboratory parameters and increased immunohistochemical reactivity for
      IL-6 antigen coincide with the presence of fever in helping to identify children
      with clinical stage B NSHD.

PMID- 8997453
TI  - Reactive oxygen species and the neurodegenerative disorders.
AB  - The major neurodegenerative disorders include Alzheimer's disease, amyotrophic
      lateral sclerosis, Parkinson's disease, and multiple sclerosis. Although their
      etiology and pathogenesis are unknown, numerous recent studies suggest that
      oxygen-derived free radicals play an important role. Furthermore, these reactive
      oxygen species are probably important in brain ischemia and reperfusion, Down's
      syndrome, and the mitochondrial encephalopathies. In this review, evidence for
      oxygen-derived free radicals in the pathogenesis of these disorders is discussed.

PMID- 8997455
TI  - Testing for inborn errors of metabolism in the acutely ill newborn.
AB  - The differential diagnosis of the acutely ill newborn should include inborn
      errors of metabolism along with much more common conditions such as sepsis and
      hypoxemia. Testing recommendations, which can take place simultaneously with
      other studies, are presented for the evaluation of inborn errors in acutely ill
      newborns. Initial hospital-based tests include arterial blood gases, glucose,
      electrolytes, urinalysis, complete blood count, and cultures. The results from
      these initial tests are used to categorize the clinical presentation into one of
      several categories, and each category in turn serves to direct further testing in
      an efficient manner. Definitive diagnosis often requires referral to a pediatric
      specialist, as well as testing available only through reference and research
      laboratories. Transfer to a tertiary care facility may be advisable when evidence
      for an inborn error is found.

PMID- 8997456
TI  - The association of antibodies to beta 2 glycoprotein I with the antiphospholipid
      syndrome: a meta-analysis.
AB  - The precise target of marker autoantibodies in the antiphospholipid syndrome
      (APS) has been controversial. Recently, the theory that surface-bound beta 2
      glycoprotein I (beta 2 GPI) presents a normally encrypted autoepitope and that
      antibodies to beta 2 GPI (anti-beta 2 GPI) are associated with APS, has been
      prominent. The literature has been searched from 1990 to 1995 (inclusive) to find
      studies in which: (1) anti-beta 2 GPI antibodies were measured and, (2) adequate
      clinical data describing the patients were included. These conditions were met in
      four studies, from August 1992 to December 1995, in which patient samples ranged
      from 15 to 39 cases, the total of the four studies being 90 cases. Applying the
      diagnostic criteria of > or = 2 clinical manifestations of APS, 65 cases had APS
      while 25 did not. For the group with APS, 58/65 (89 percent) were anti-beta 2 GPI
      (+); among those who did not meet the criteria, 11/25 (44 percent) were anti-beta
      2 GPI (+) (p < 0.0001). The presence of either the primary (1 degree) or
      secondary (2 degrees) form of APS made no difference in association with anti
      beta 2 GPI; 13/16 (81 percent) patients with 1 degree APS and 45/49 (92 percent)
      with 2 degrees APS had anti-beta 2 GPI. The presence of lupus anticoagulant (LAC)
      did not predict APS: 25/58 (38 percent) APS (+) cases were LAC (+); 11 APS (-)
      were all LC (+) (p < 0.0001). IgG anticardiolipin also showed a closer
      association with APS absence (25/25 cases; 100 percent) than with APS presence
      (40/65; 62 percent, p < 0.0001). These data support the contention that anti-beta
      2 GPI antibodies are closely associated with APS and that their measurement may
      facilitate the diagnosis.

PMID- 8997457
TI  - Current applications of molecular cytogenetic technologies.
AB  - This review discusses select current applications of fluorescent in situ
      hybridization (FISH) which may be of utility for the average clinical cytogenetic
      laboratory. Owing to the large number of men and women affected, the applications
      chosen to illustrate the use of FISH technology in cancer focus on two diseases:
      breast cancer and prostate cancer. The applicability of FISH to detect common
      aneuploidies, such as trisomy 21, trisomy 18, trisomy 13 and the sex chromosome
      aneuploidies in prenatal diagnosis, is discussed, as well as FISH for the
      detection of microdeletions and microduplications. Quality assurance/quality
      control issues and standards and guidelines relating to laboratory practices in
      molecular cytogenetic testing are reviewed.

PMID- 8997459
TI  - Cost comparison of recombinant human erythropoietin and blood transfusion in
      cancer chemotherapy-induced anemia.
AB  - OBJECTIVE: To compare the cost of recombinant human erythropoietin (rHuEPO) with
      that of blood transfusion in the treatment of chemotherapy-induced anemia from a
      healthcare system perspective. DESIGN: A decision analytic model. Baseline
      estimates were obtained from a review of clinical trials data and economic
      evaluation studies. SUBJECTS: Secondary data analyses of patients with advanced
      malignancies, excluding hematologic malignancies and metastasized solid tumors.
      INTERVENTIONS: Patients received either leukocyte-depleted packed red blood cells
      (PRBCs) or rHuEPO 150 units/kg s.c. three times per week for 6 months (24 wk).
      After 6 weeks, if rHuEPO recipients did not display a response, they received
      rHuEPO 300 units/kg s.c. three times weekly for the duration of therapy. If
      rHuEPO recipients still exhibited no response, they were given blood
      transfusions. MEASUREMENTS AND MAIN RESULTS: For a treatment period of 24 weeks,
      approximately 64% of rHuEPO recipients responded at an average expected cost of
      $12971 per patient. One hundred percent of transfusion recipients responded at a
      cost of $481; this resulted in a cost savings of $8490. Variation of response
      rates for rHuEPO or PRBCs did not appreciably lower costs. Lower rHuEPO dosages
      and higher numbers of transfused units of PRBCs yielded approximately equivalent
      costs; however, these strategies may not be clinically prudent. CONCLUSIONS: From
      a healthcare system cost and outcome perspective, blood transfusion is the
      preferred strategy for chemotherapy-induced anemia. However, rHuEPO may be
      considered an effective blood-sparing alternative for patients with non-stem cell
      disorders. Future cost-effectiveness analyses are needed to assess more
      completely both the clinical and quality-of-life benefits rHuEPO may contribute
      to individual patients' lives and to society overall.

PMID- 8997458
TI  - Protection of ethanol-mediated acetaminophen hepatotoxicity by
      triacetyloleandomycin, a specific inhibitor of CYP3A.
AB  - Cytochrome P450 2E (CYP2E) is considered responsible for ethanol-mediated
      increases in acetaminophen (APAP) hepatotoxicity. However, it has been shown in
      cultured human and rat hepatocytes and intact rats that ethanol induces CYP3A in
      addition to CYP2E. Therefore, an investigation was made in rats to see whether or
      not an inhibitor of CYP3A, triacetyloleandomycin (TAO), would protect against
      ethanol-mediated increases in APAP hepatotoxicity. Rats, treated with 6.3 percent
      ethanol in the Lieber-DeCarli diet for 7 days, were administered APAP (lg/kg,
      i.g.) 11 hrs after removal of the diet. Triacetyloleandomycin (500 mg/kg, saline
      solution) was injected i.p. 2 hrs before the administration of APAP. In rats
      pretreated with ethanol, treatment with APAP for 7 hrs resulted in focal
      centrilobular congestion and steatosis. Triacetyloleandomycin completely
      prevented the histological liver damage in all 8 animals. These results suggest
      that, in ethanol-treated rats, CYP3A plays a major role in increasing APAP
      hepatotoxicity.

PMID- 8997460
TI  - Site-specific pharmacokinetics and pharmacodynamics of intramuscular meperidine
      in elderly postoperative patients.
AB  - OBJECTIVE: To examine and compare the pharmacokinetics and pharmacodynamics of
      meperidine when administered intramuscularly at gluteal and deltoid sites in
      elderly postoperative patients. DESIGN: Prospective, randomized investigation.
      SETTING: Tertiary care university teaching hospital. PATIENTS: Fourteen patients
      60 years of age or older who were undergoing general surgery. INTERVENTION: A
      single dose of meperidine 0.75 mg/kg given intramuscularly at either a deltoid or
      gluteal site. MAIN OUTCOME MEASURES: Pharmacokinetic (based on concentration-time
      curves) and pharmacodynamic (i.e., pain scales, need for additional pain
      medication) comparisons were made, based on site of meperidine injection.
      RESULTS: No statistically significant differences were found in the maximum
      plasma concentration, volume of distribution, or clearance of meperidine by site
      of injection. Substantial interpatient variability in pharmacokinetic parameters
      was noted for both sites (range of maximum concentrations: 191-500 ng/mL gluteal,
      166-374 ng/mL deltoid). Although pain scores were similar for the two groups,
      four of the patients in the group given gluteal injection required additional
      breakthrough pain management within 4 hours of meperidine injection compared with
      one patient in the group given deltoid injection. CONCLUSIONS: There is no
      obvious relationship between meperidine pharmacokinetic and pharmacodynamic
      parameters, regardless of intramuscular injection site. Breakthrough pain is
      common when patients are given intramuscular injections postoperatively,
      particularly when the gluteal route is used. When meperidine is used for
      analgesia in elderly postoperative patients, consideration should be given to
      more rapid and predictable routes (e.g., intravenous injection) of meperidine
      administration.

PMID- 8997461
TI  - Mexiletine in the symptomatic treatment of diabetic peripheral neuropathy.
AB  - OBJECTIVE: To evaluate the efficacy and safety of mexiletine in the symptomatic
      treatment of diabetic peripheral neuropathy (DPN). METHODS: In this prospective,
      double-blind study, 29 patients were randomized to receive mexiletine 600 mg/d or
      matching placebo for 3 weeks. A four-item symptom score (FIS), which rated pain,
      dysesthesias, paresthesias, and nightly exacerbations of symptoms, and a 100-mm
      visual analog scale (VAS), which rated pain intensity, were completed by patients
      before and after treatment. At the end of treatment independent patient and
      investigator global assessments were made. Patients reported adverse effects
      after 1 and 3 weeks of treatment. RESULTS: Treatment groups were similar at
      baseline. The difference between the median changes in FIS scores (mexiletine =
      5.5, placebo = 2) was not statistically significant. Overall symptom response was
      similar in both treatment groups as demonstrated by both global assessments (p =
      0.19). The mean change in VAS score from baseline to posttreatment was determined
      for both groups and the difference between these mean scores was 16.5 mm (95% CI,
      -7.1 to 40.2 mm) (p = 0.16). Inadequate statistical power (1-beta = 0.40) may
      have resulted from small sample size, small magnitude of effect, or variability
      in the measured effect. Adverse effects were more common in the mexiletine group,
      though not statistically significant. One patient receiving mexiletine was
      hospitalized for palpitations. CONCLUSIONS: Because of conflicting reports of
      mexiletine's efficacy in the treatment of symptomatic DPN, this drug should be
      reserved for patients unresponsive or intolerant to standard therapy, without
      evidence of heart disease, and with sensations of burning heat, formication, or
      stabbing pain.

PMID- 8997463
TI  - Amphotericin B enzyme-linked immunoassay for clinical use: comparison with
      bioassay and HPLC.
AB  - OBJECTIVE: To evaluate a new enzyme-linked immunosorbent assay (ELISA) for
      amphotericin B in serum samples. Results are compared with those obtained by HPLC
      and bioassay. DESIGN: Comparison of results obtained by ELISA, HPLC, and
      bioassay. METHODS: We developed a new ELISA using a polyclonal rabbit antibody to
      measure serum amphotericin B concentrations. Blinded samples of amphotericin B in
      concentrations of 0.15-78 micrograms/mL were prepared in human serum and assayed
      simultaneously by the ELISA, HPLC, and bioassay. The results of each assay were
      derived from standard curves and evaluated by using the Table Curve 2D computer
      program. These data were compared by using correlation analysis with evaluation
      of Pearson's correlation coefficient by Student's t-test. RESULTS: ELISA and
      bioassay compared favorably at amphotericin B concentrations of 0.3-20
      micrograms/mL with a correlation coefficient of r = 0.993, while ELISA and HPLC
      compared with a correlation coefficient of r = 0.944. The average coefficient of
      variation over the range 0.3-20.0 micrograms/mL was 28% +/- 7% for HPLC, 26% +/-
      9% for ELISA, and 13% +/- 4% for bioassay. Comparison of all three assays
      revealed the highest correlation with the ELISA assay (r = 0.998) for the range
      of concentrations (0.3-20 micrograms/mL) routinely achieved. Samples containing
      concentrations in excess of 20 micrograms/mL could be diluted. Desiccation for
      concentrations less than 0.3 microgram/mL was not tested. CONCLUSION: The
      determination of serum amphotericin B concentrations by ELISA gave results
      similar to those obtained by a bioassay and HPLC technique. Although variability
      appears greater with ELISA, the ease of performing yjis assay expedites the
      evaluation of amphotericin B concentrations from lipid formulations without
      interference from coadministered antibacterials of azole antifungals.

PMID- 8997462
TI  - Clinical investigation of topical antimicrobials in healthy volunteers.
AB  - OBJECTIVE: To evaluate the antibacterial activity, onset of action, and duration
      of action of four topical antimicrobial gels containing cetrimide, bacitracin,
      polymyxin B sulfate, and a placebo gel. DESIGN: Multiples (1 x, 2x, 4x, 8x) of
      minimally inhibitory in vitro drug concentrations were formulated in a gel
      vehicle. Antibacterial activity was evaluated using a scrub-wash methodology on
      artificially inoculated skin over an 8-hour study period. SETTING AND
      PARTICIPANTS: Healthy volunteers with intact forearm skin participated in the
      study. A standardized culture of Staphylococcus aureus NCTC 6571 was applied to
      four areas on each forearm, randomly assigned topical treatments were applied,
      and sites were sampled at predetermined time intervals using a surfactant wash
      fluid. OUTCOME MEASURES: Recovered bacteria were quantitated, allowing a
      comparison of antibacterial activity. RESULTS: Two-way and one-way ANOVA and a
      Scheffe test confirmed significant differences in antibacterial effect between
      the formulations containing 4 and 8 times the minimally inhibitory in vitro
      concentrations and placebo (p < 0.05). Duration of action was similar for all
      preparations; however, onset appeared to be faster with the formulations
      containing 4 and 8 times minimally inhibitory in vitro concentrations.
      CONCLUSIONS: The two topical preparations containing 4 and 8 times the minimally
      inhibitory in vitro concentrations of cetrimide, bacitracin, and polymyxin B
      sulfate demonstrated significant antibacterial activity and may have potential
      for further clinical investigations.

PMID- 8997464
TI  - Evaluation of drug interaction document citation in nine on-line bibliographic
      databases.
AB  - OBJECTIVE: To compare nine on-line bibliographic databases to obtain
      bibliographic references on specific drug interactions. DESIGN: Seven
      bibliographic databases were selected for their ability to provide information
      concerning drug interactions: EMBASE, MEDLINE, TOXLINE, BIOSIS, Chemical
      Abstracts (CAS), PHARMLINE, and International Pharmaceutical Abstracts (IPA). Two
      French on-line bibliographic databases (i.e., PASCAL, BIBLIOGRAPHIF) were also
      tested to compare them with the other international databases. Twenty drug
      interactions were selected randomly using the journal Reactions Weekly 1993. MAIN
      OUTCOMES MEASURES: The total number of references, the number of potentially
      relevant references, the number of case report references, the number of unique
      references in the total number of references, and the number of unique references
      between potentially relevant references were analyzed by using the Friedman two
      way ANOVA by ranks. For each database, relevance and relative recall were
      calculated. RESULTS: For the total number of references, EMBASE was significantly
      more comprehensive then all other databases (p < 0.05). EMBASE had a
      significantly greater number of potentially relevant references than IPA,
      PHARMLINE, CAS, and BIBLIOGRAPHIF (p < 0.05). For the total number of case report
      references, only one significant difference, between EMBASE and BIBLIOGRAPHIF (p
      < 0.05), was observed. MEDLINE and TOXLINE had the lowest cost per potentially
      relevant reference. CONCLUSIONS: To obtain bibliographic references on drug
      interactions, the first step should be to search MEDLINE or TOXLINE; the second
      step, for completeness, should be to search EMBASE.

PMID- 8997465
TI  - Severe vaginal bleeding associated with recombinant interferon beta-1B.
AB  - OBJECTIVE: To report a case of severe vaginal bleeding associated with interferon
      beta-1b (IFN-beta). CASE SUMMARY: A 19-year-old white woman diagnosed with
      multiple sclerosis was treated with IFN-beta 4 million IU every other day for 1
      month. After 1 month, the dosage was increased to 8 million IU. The patient
      subsequently experienced severe vaginal bleeding. Because her hemoglobin was 3.9
      g/dL, she was admitted to the hospital for treatment and observation. IFN-beta
      was discontinued and she was treated with conjugated estrogens and received 2
      units of packed red blood cells. The bleeding ceased and the patient was
      discharged in stable condition. DISCUSSION: Menstrual disorders of mild-to
      moderate severity were reported during clinical trials with IFN-beta. This is the
      first case report regarding severe vaginal bleeding probably associated with IFN
      beta. The mechanism for development of IFN-beta-related menstrual disorders is
      unknown. CONCLUSIONS: Reports of menstrual disorders associated with recombinant
      IFN-beta are rare; however, clinicians should be aware that this complication can
      occur. Should menstrual disorders occur with no other etiologic factors
      identified, IFN-beta should be discontinued, with improvement expected shortly
      thereafter.

PMID- 8997466
TI  - Metformin-associated nonketotic metabolic acidosis.
AB  - OBJECTIVE: To document a case of anion gap, nonketotic metabolic acidosis
      occurring in a patient with acute renal failure who was receiving metformin. CASE
      SUMMARY: A 67-year-old white man presented with a 9-day history of weakness,
      nausea, dizziness, and difficulty moving; he had also not eaten during the
      previous 2 days. The patient had numerous abnormalities on his serum chemistry
      panel and arterial blood gases, including a pH of 7.1 and an anion gap of 21
      mEq/L No ketones were detected in the urine. The patient was treated with
      intravenous fluids, sodium bicarbonate, insulin, and hemodialysis. All
      medications were discontinued. The acidosis resolved shortly after hemodialysis.
      The hospital course was complicated by the onset of atrial fibrillation occurring
      on day 2 that did not respond to chemical cardioversion. On day 6 the patient was
      discharged home with resolving acute renal failure and normal serum pH.
      CONCLUSIONS: The mortality rate of biguanide-induced lactic acidosis is
      approximately 50%; thus, early recognition and treatment are essential. Suspicion
      of lactic acidosis should be high when diabetic patients who are taking a
      biguanide present with acidosis. The majority of cases of metformin-induced
      lactic acidosis have occurred in patients with contraindications to the drug
      (i.e., renal dysfunction). Thus, it is important to maintain strict adherence to
      these contraindications and monitor patients for deteriorating renal function.

PMID- 8997467
TI  - Rhabdomyolysis induced by epsilon-aminocaproic acid.
AB  - OBJECTIVE: To report a case of rhabdomyolysis associated with epsilon
      aminocaproic acid (epsilon-ACA). CASE SUMMARY: A 33-year-old female patient with
      chronic granulocytic leukemia was treated with epsilon-ACA for approximately 3.5
      months for thrombocytopenic bleeding. The initial dosage was 4 g po q6h. One
      month after an increase in dosage to 5 g po 14h the patient developed severe
      lower extremity myalgia and marked weakness. Laboratory investigations revealed
      an elevated creatine kinase (CK), lactate dehydrogenase (LDH). aspartate
      aminotransferase (AST), and myoglobinemia. Epsilon-ACA was thought to be the
      causative agent and was discontinued. The patient received intravenous fluids to
      minimize renal damage due to myoglobin. Serum enzyme concentrations did not
      return to normal. The patient died of a central nervous system hemorrhage 1 week
      after the epsilon-ACA was discontinued. DISCUSSION: There were 31 cases of
      epsilon-ACA-induced myopathies published in the literature (MEDLINE) from 1972 to
      June 1995. Of these, 10 cases were reviewed. In all cases, patients received
      epsilon-ACA in doses ranging from 16 to 36 g/d for more than 28 days. Clinical
      findings varied from extreme muscle weakness to myopathic changes in
      electromyelograms. All patients recovered following discontinuation of epsilon
      ACA. CONCLUSIONS: Long-term therapy with high-dose epsilon-ACA may produce muscle
      weakness or rhabdomyolysis. Patients who require long-term, high-dose epsilon-ACA
      therapy should be monitored for myoglobinuria and changes in serum CK, LDH, and
      AST, for myoglobinemia, for decreases in muscle strength, and/or for myalgia.
      Significant changes in these parameters compared with baseline values should
      suggest a need to discontinue epsilon-ACA therapy.

PMID- 8997468
TI  - Sulfadiazine-induced sialadenitis.
AB  - OBJECTIVE: To present a case of sialadenitis induced by sulfadiazine. CASE
      SUMMARY: A 50-year-old man with bronchitis developed swelling of the parotid
      glands and floor of the mouth as well as plugging in his ears 2 hours after
      ingestion of Bronco-aseptilex (sulfadiazine, cyclamate, and guaiacol). Skin-prick
      tests performed with serial dilutions of sulfadiazine and Bronco-aseptilex were
      all negative. We then performed oral challenge tests with Bronco-aseptilex,
      sulfadiazine, and other compounds of the commercial syrup. Enlargement of the
      salivary glands was observed after oral challenge tests with Bronco-aseptilex and
      sulfadiazine. CONCLUSIONS: We describe a patient who developed drug-induced
      sialadenitis. The oral challenge test confirmed that sulfadiazine was the
      etiologic agent.

PMID- 8997469
TI  - Hazards of doubling phenytoin dose in the face of an unrecognized interaction
      with ciprofloxacin.
AB  - OBJECTIVE: To underscore the need for caution when making dramatic changes in
      phenytoin dosing, and to report a possible ciprofloxacin interaction in which
      failure of seizure control led to inappropriately high phenytoin dosing and
      subsequent intoxication. CASE SUMMARY: A 61-year-old African-American man
      receiving long-term therapy with phenytoin 100 mg po tid for seizures secondary
      to a stroke was admitted for community-acquired pneumonia. His serum phenytoin
      concentration at admission was therapeutic at 12.6 micrograms/mL. Eight days
      after admission, ciprofloxacin 750 mg po bid was started for possible aspiration.
      Two days later he experienced a seizure; the serum phenytoin concentration was
      2.5 micrograms/mL. In response to the 80% decline in phenytoin concentration, the
      dosage was gradually titrated upward to produce a serum concentration of 12.6
      micrograms/mL. This eventually required a doubling of the original phenytoin
      dosage and he was discharged on 200 mg po tid. The patient subsequently developed
      severe ataxia and sustained a head injury for which he was seen again in the
      emergency department. Serum phenytoin concentration at that time was 42.8
      micrograms/mL. Concentrations declined at a normal rate when phenytoin was
      withheld. CONCLUSIONS: It appears that a rapid decline in phenytoin concentration
      during the first admission was related to coadministration of ciprofloxacin,
      either through inhibition of absorption or induction of metabolism. In a
      conscientious effort to titrate phenytoin concentrations back to therapeutic
      values, the issue as to why this required such a dramatic change in dosage was
      ignored. Thus, in trying to prevent further seizures, the patient was unknowingly
      placed in jeopardy a second time when his usual dosage of phenytoin was doubled.
      As a result, phenytoin intoxication ensued after discharge when the ciprofloxacin
      was discontinued. This case illustrates a potentially dangerous interaction
      between ciprofloxacin and phenytoin, and it underscores the need to maintain a
      high index of clinical suspicion for drug interactions in any patient requiring a
      substantial change in drug dosage.

PMID- 8997470
TI  - Nilutamide: an antiandrogen for the treatment of prostate cancer.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse
      effects of nilutamide and to compare this agent with the currently marketed
      nonsteroidal antiandrogens (i.e., bicalutamide, flutamide) by critically
      analyzing the published literature. DATA SOURCES: MEDLINE (1980-1995) and
      CANCERLIT (1991-1995) were searched for English-language publications using the
      terms nilutamide, bicalutamide, and flutamide alone, and either nilutamide or
      androgen antagonists in combination with prostatic neoplasms. STUDY SELECTION AND
      DATA EXTRACTION: All articles with subject matter on nilutamide, bicalutamide,
      and flutamide were considered for inclusion. For studies published in more than
      one journal, the first publication was used unless a subsequent publication
      included additional or follow-up data, in which case the latter publication was
      cited instead. DATA SYNTHESIS: Nilutamide was effective in combination with
      orchiectomy in improving responses in patients with advanced prostate cancer.
      However, patient survival was not improved in these trials, and improvements in
      bone pain did not usually result in improved performance status in these
      patients. The few trials of nilutamide monotherapy or nilutamide in combination
      with a luteinizing hormone-releasing hormone analog are too small to draw
      meaningful conclusions regarding its efficacy or its role in the treatment of
      advanced prostate cancer. No comparative trials of nilutamide with other
      antiandrogens and no analysis of the impact of nilutamide on patient quality of
      life are currently available. Nilutamide appears to produce a higher frequency of
      adverse effects than the other currently marketed nonsteroidal antiandrogens,
      bicalutamide and flutamide. CONCLUSIONS: Nilutamide does not appear to represent
      a major advance in the treatment of advanced prostate cancer and appears to be
      somewhat inferior to both flutamide and bicalutamide with regard to adverse
      effects. Nilutamide should not be considered the antiandrogen of choice in the
      treatment of advanced prostate cancer.

PMID- 8997471
TI  - Apoptosis: its role in the development of malignancies and its potential as a
      novel therapeutic target.
AB  - OBJECTIVE: To review the current literature regarding the role of apoptosis in
      the development of malignant cells and how the induction of this pathway could be
      used in cancer therapy. DATA SOURCE: A MEDLINE search of basic science articles
      pertinent to the understanding of the normal physiologic process of apoptosis was
      conducted. STUDY SELECTION: Because of the rapidly growing literature regarding
      apoptosis, only articles describing key processes in the biology of the cell and
      the genetic control of apoptosis were included. DATA SYNTHESIS: Apoptosis is
      imperative for host survival since it discards unwanted, damaged, and atypical
      cells. The process is therefore implicated in the continuous regulation of
      development, differentiation, and homeostasis. Furthermore, apoptosis is a
      response to physiologic and pathologic stresses that disrupt the balanced rates
      of cell generation and elimination. In a disease such as cancer, there is a lack
      of equilibrium between the rates of cell division and cell death; agents that
      promote or suppress apoptosis can manipulate these rates, influencing the
      anomalous accumulation of neoplastic cells. Pharmacologic manipulation of
      apoptosis can manipulate these rates, influencing the anomalous accumulation
      represents a novel approach in targeting malignant cells and has far-reaching
      implications for new directions in cancer therapy. CONCLUSIONS: Apoptosis is a
      highly organized physiologic mechanism of destroying injured and abnormal cells
      as well as maintaining homeostasis in multicellular organisms. Both the
      activation and inhibition of apoptosis are tightly controlled. Pharmacologic
      manipulation of this pathway is a novel therapeutic target in cancer therapy.

PMID- 8997472
TI  - Respiratory syncytial virus immune globulin intravenous.
AB  - OBJECTIVE: To review the clinical data detailing the use of respiratory syncytial
      virus immune globulin intravenous (RSV-IGIV) in infants and children. DATA
      SOURCES; A MEDLINE search (1990-1996) was used to identify all publications that
      dealt with RSV-IGIV clinical trials, pharmacology, and pharmacokinetics in
      infants and children. Bibliographies of articles were also used. STUDY SELECTION:
      All abstracts and clinical trials were reviewed. DATA EXTRACTION: Study design,
      population, efficacy, and safety data were retained. DATA SYNTHESIS: RSV-IGIV is
      an immunoglobulin product with serum neutralizing titers against RSV. It has been
      shown to reduce hospital stay, admissions, intensive care unit admissions, and
      mechanical ventilation days in infants and children with RSV pneumonia or
      bronchiolitis who are younger than 24 months of age and were born prematurely, or
      have bronchopulmonary dysplasia. RSV-IGIV is well tolerated by infants and
      children. CONCLUSIONS: RSV-IGIV is an effective prophylactic agent against
      serious RSV disease in select groups of infants and children.

PMID- 8997474
TI  - Lipoprotein disorders in women: which women are the best candidates for hormone
      replacement therapy?
AB  - OBJECTIVE: To review the data examining hormone replacement therapy (HRT) in the
      treatment of lipoprotein disorders in women. DATA SOURCE: A MEDLINE search (1975
      1995) of the English-language literature was performed to identify pertinent
      primary literature and review articles. Articles were also identified through
      bibliographies of selected articles. DATA EXTRACTION: Controlled and uncontrolled
      studies evaluating the effects of lipoprotein concentrations or coronary risk and
      the effects of estrogen and HRT on coronary heart disease and lipoprotein
      concentrations in women were evaluated. Trials pertaining to adverse effects of
      therapy were also examined. Emphasis was placed on recent clinical trials. DATA
      SYNTHESIS: The National Cholesterol Education Program's (NCEP's) 1993 report
      recommends estrogen replacement therapy as a treatment option in postmenopausal
      women with hyperlipidemia. Recent trials suggesting that triglycerides and highly
      density lipoproteins are more closely related to coronary risks in women
      necessitate an improved understanding of estrogen and progestin's effects of
      lipoprotein concentrations. A recent trial has clarified the lipoprotein effects
      of HRT in women with normal lipid concentrations and suggests that beneficial
      effects on low-density lipoproteins are maintained, although progestins attenuate
      beneficial changes in high-density lipoproteins and triglyceride elevations
      persist. The few trials evaluating estrogen use in women with hyperlipidemia
      suggest a beneficial effect as well. CONCLUSIONS: In the absence of
      contraindications, postmenopausal women with hyperlipidemia should be offered
      estrogen replacement therapy as conjugated equine estrogen of 0.625 mg/D. Pending
      further information. NCEP's recommendations should be followed regarding goals of
      therapy.

PMID- 8997473
TI  - "Isolated" low high-density lipoprotein cholesterol.
AB  - OBJECTIVE: To present information on the function, structure, and importance of
      high-density lipoprotein cholesterol (HDL-C) and to evaluate the current
      literature regarding the controversy of managing patients with an "isolated" low
      HDL-C concentration. DATA SOURCE: A MEDLINE search was performed (1966-June 1996)
      to identify English-language clinical and review articles pertaining to HDL-C.
      Some articles were identified through the bibliography of selected articles.
      STUDY SECTION: All articles were considered for possible inclusion in the review.
      Pertinent information, as judged by the authors, was selected for discussion.
      DATA EXTRACTION: Important historical lipid studies, recent review articles, and
      clinical trials involving therapy for HDL-C were evaluated. DATA SYNTHESIS: The
      structure, function, and measurement of HDL-C and the state of an isolated low
      HDL-C are discussed for background. Lifestyle modification measures to increase
      HDL-C, medications to avoid, estrogen replacement, and lipid-altering agents used
      to raise an isolated low HDL-C are presented. CONCLUSIONS: An isolated low HDL-C
      concentration poses a risk for coronary heart disease. The management of this
      state is controversial. The first step in management is in agreement with experts
      and includes lifestyle modification (e.g., weight reduction, diet, smoking
      cessation, aerobic exercise). Estrogen replacement therapy and discontinuance of
      drugs that secondarily lower HDL-C are additional treatment options. The use of
      lipid-altering agents has been used in some patients. Nicotinic acid appears to
      be an effective agent for an isolated low HDL-C. A large clinical trial
      evaluating the effect of treating an isolated low HDL-C for primary and secondary
      prevention of coronary events is needed.

PMID- 8997475
TI  - Association of SIADH with selective serotonin reuptake inhibitors.
AB  - While SSRIs have been reported to cause SIADH, the actual incidence remains
      unclear. From the published case reports, the elderly may appear to be at higher
      risk of developing SIADH. Symptomatic and laboratory presentation in these
      patients includes lethargy, hyponatremia, elevated urinary sodium excretion, and
      hyperosmolar urine. However, evaluation of SSRI-induced SIADH has been
      incomplete. Normalization of serum sodium concentrations occurred after
      discontinuation of the SSRI and/or fluid restriction. Of the published reports,
      only three convincingly demonstrated a causative role of SSRI-induced SIADH by
      rechallenge. As a result, the published case reports cannot definitely
      established a causal relationship. Pharmacists can play an important role in the
      care of patients with suspected SSRI-induced SIADH. Pharmacists should be
      familiar with the clinical and biochemical presentation of SIADH as well as the
      limitations of published case reports implicating SSRIs as a cause of SIADH. A
      complete medication history, including when these agents were initiated or
      discontinued, should be taken. Pharmacists must understand, recognize, and ensure
      the proper monitoring parameters, namely daily fluid intake, patient weight, and
      serum sodium concentrations.

PMID- 8997476
TI  - Chemoprophylaxis for group B streptococcus transmission in neonates.
AB  - GBS causes infection in 1.35-5.4 neonates per 1000 live births. Early-onset GBS
      infection in neonates develops rapidly and has a high mortality rate. Preventing
      the transmission of GBS to neonates is of considerable value to avert neonatal
      morbidity and mortality. Although some controversy exists regarding who should
      receive chemoprophylaxis and when, AAP guidelines suggest that all pregnant women
      be screened between 26 and 28 weeks' gestation for GBS colonization by obtaining
      swabs form vagina and anorectal areas and culturing them or testing by rapid
      antigen test. According to the latest guidelines from the CDC, any pregnant woman
      who tests positive for GBS and who has one or more risk factors should be given
      intrapartum penicillin 5 million units i.v. as the first dose and then 2.5
      million units q6h until delivery. Ampicillin, in a dosage of 2 g as the first
      dose and then 1 g every 4-6 hours may be used as an alternative. Patients who are
      allergic to penicillin can be given either erythromycin 500 mg i.v. q6h or
      clindamycin 600 mg i.v. q8h. The chemoprophylaxis is primarily effective for
      early-onset GBS infection; for late-onset infection, aggressive treatment of the
      neonate should be initiated promptly with ampicillin and gentamicin. Although
      many studies have been published that establish the efficacy of ampicillin for
      intrapartum GBS prophylaxis, there is a need for large-scale studies to show the
      efficacy of both erythromycin and clindamycin. Various vaccines are under
      development for maternal administration to prevent the transmission of GBS to
      neonates. When one is available, it will be an added weapon against GBS.

PMID- 8997477
TI  - Fish oil therapy in IgA nephropathy.
AB  - IgA nephropathy often progresses to endstage renal failure over a period of many
      years, and any therapy directed to IgA nephropathy will most likely have to be
      administered over an extended period of time. Therefore, optional therapy should
      be effective and free of long-term adverse effects. Besides fish oil, prednisone
      has also been investigated for treatment of IgA nephropathy, with a lack of
      consistent results; severe adverse effects are common with long-term use. Several
      studies have shown positive although not overly impressive results; therefore
      optimal therapy for slowing the progression of renal failure secondary to IgA
      nephropathy has not been established. Problematic issues with available studies
      included the following: (1) most of the clinical studies previously discussed
      were short-term, contained small numbers of patients, and most but not all were
      uncontrolled; (2) early reports involving fish oil therapy demonstrated
      conflicting results regarding its efficacy, including one study that observed
      increased progression of renal disease in patients treated with fish oil;
      however, recent studies have shown more promise for fish oil therapy for up to 2
      years of treatment; and (3) since most of the studies were conducted over a short
      period of time, it is difficult to assess long-term effects and safety of oil
      treating IgA nephropathy, a disease that progresses to ESRD over 10-20 years.
      However, given the low number of adverse effects and apparent low risks
      associated with this relatively safe food supplement therapy observed in most
      clinical trials of up to 2 years duration, fish oil may slow the progression of
      renal failure in patients with IgA nephropathy. Therefore, with appropriate
      monitoring of renal function and blood tests, treatment with fish oil 6-12 g/d
      should be considered in patients with IgA nephropathy.

PMID- 8997478
TI  - Interpreting and using information from studies without statistical significance.

PMID- 8997479
TI  - Fluconazole treatment for vulvovaginal candidiasis during pregnancy.

PMID- 8997480
TI  - Carbidopa/levodopa in the treatment of neuroleptic malignant syndrome.

PMID- 8997481
TI  - Anaphylactoid reaction to ciprofloxacin versus toxic shock syndrome.

PMID- 8997482
TI  - Tendinitis associated with ciprofloxacin.

PMID- 8997483
TI  - Potentially toxic self-treatment of uremic pruritus with topical pyrethroid
      insecticides.

PMID- 8997484
TI  - Nutritional impact of lipid-associated amphotericin B formulations.

PMID- 8997485
TI  - Probable interaction between cetirizine and acenocoumarol.

PMID- 8997486
TI  - Biology: an expanding universe--or is convergence to a few principles around the
      corner?

PMID- 8997487
TI  - Retroviral proteases: structure, function and inhibition from a non-anticipated
      viral enzyme to the target of a most promising HIV therapy.
AB  - Retrovirally encoded proteases are responsible for the maturation of immature
      viral particles yielding mature, infectious virus. This is done by apparent
      (auto)-processing and self-activation of the protease (PR) from a larger viral
      gag-PR-(pol) protein (zymogen) precursor and subsequent processing of the viral
      reverse transcriptase (RT) and integrase (IN), and the gag protein precursor into
      mature gag proteins. Only the matured components are capable of forming capsids
      for intact, infectious viruses. Blocking this proteolytic process results in
      production of immature, non-infective virions. All retroviral proteases are
      aspartic-type proteases. Determination of the three-dimensional structure
      revealed retroviral proteases as small, nearly symmetric homodimers. This
      prompted de novo design of inhibitors for the HIV protease taking advantage of
      the unique symmetric structure of the active center, unparalleled by cellular
      proteases. The novel substances inhibit in vitro the HIV protease at
      nanomolar/subnanomolar concentrations and exhibit very low toxicity. They are
      inactive against human proteases such as renin or pepsin. The HIV protease
      inhibitors (PI) represent a promising alternative to the reverse transcriptase
      (RT) inhibitors (AZT, ddC, ddI) hitherto used with limited success for HIV
      chemotherapy. Clinical studies confirmed the low toxicity but revealed a
      pharmacological pattern typical for these hydrophobic compounds, such as low
      water solubility, poor oral bioavailibility, and short plasma half-life. Typical
      for antimicrobial agents, also a resistance phenomenon became evident. Latest
      clinical results show, however, promisingly that both problems might be overcome
      by application of the PI in combination with RT inhibitors (such as AZT, ddI or
      ddC) exerting a remarkable synergistic antiviral effect with lasting restoration
      of the CD4-T-cell level.

PMID- 8997488
TI  - Mechanisms of nonhomologous DNA end-joining in frogs, mice and men.
AB  - DNA end-joining, a process related to illegitimate recombination and capable of
      rejoining unrelated pairs of DNA ends in the absence of sequence homology, is
      considered the major pathway of double-strand break (DSB) repair in mammalian
      cells. Whole cell and nuclear extracts from three human and one mouse cell line
      were investigated for their capacities to promote nonhomologous DNA end-joining
      and their relative activities of DNA-PK, a mammalian DNA end-binding protein
      complex implicated in DSB-repair. The levels of DNA end-joining and the spectra
      of junctions of the human systems were identical with the ones of a previously
      described cell-free joining system derived from Xenopus laevis eggs. Due to the
      presence of potent 3'-5'-exonuclease activities the mouse system displayed
      decreased levels of DNA end-joining and larger fractions of junctions containing
      deletions but otherwise the basic mechanisms of junction formation appeared to be
      identical with the Xenopus system. DNA-PK activity was found to be equally low in
      the Xenopus and the mouse system but 4- to 6-fold increased in the human systems.
      Our results suggest that the mechanisms of DNA end-joining may be modulated by
      the level of exonuclease activities and/or DNA end-protecting factors but are
      otherwise highly conserved in vertebrate cells.

PMID- 8997489
TI  - Recombinant bovine herpesvirus-1 (BHV-1) lacking transactivator protein BICPO
      entails lack of glycoprotein C and severely reduced infectivity.
AB  - The immediate-early transactivator protein BICPO is a key regulatory element of
      bovine herpesvirus 1 (BHV-1) replication based on transient expression assays. To
      examine BICPO function in the context of the viral genome, we created recombinant
      BHV-1 expressing beta-galactosidase instead of BICPO. To complement the defect, a
      neomycin resistant MDBK cell line (M164) expressing BICPO was established,
      permitting selection of a blue-staining BHV-1 recombinant (A2G2). Southern blot
      and PCR analysis confirmed that the BICPO gene was interrupted by the beta
      galactosidase gene and that wt progeny was absent. Compared with wt BHV-1, A2G2
      reached lower titers in M164 cells but replicated with similar kinetics. Once
      isolated, A2G2 also grew in MDBK cells although the titer was reduced a further
      10-fold and the virus remained strongly cell-associated. Thus, BICPO is not
      absolutely required for replication in cell culture. Gene expression of A2G2 was
      investigated by Western blots and immunofluorescence. Surprisingly, not only was
      BICPO absent, but glycoprotein C (gC) was also missing. Other viral genes were
      expressed normally. Semiquantitative PCR showed that A2G2 produced similar
      amounts of viral DNA as wt but a much smaller number of infectious particles.
      Cotransfection of A2G2 DNA and a plasmid containing the BICPO gene yielded
      revertant virus with fully restored wt properties. We conclude that BICPO is
      required for gC expression, and that the missing gC partly accounts for the
      reduced A2G2 infectivity.

PMID- 8997490
TI  - DNA-binding specificity of PAR and C/EBP leucine zipper proteins: a single amino
      acid substitution in the C/EBP DNA-binding domain confers PAR-like specificity to
      C/EBP.
AB  - PAR and C/EBP family proteins are liver-enriched basic leucine zipper (bZip)
      transcription factors that bind similar sites on the promoters of albumin and
      cholesterol 7 alpha hydroxylase genes. However, C/EBP proteins have a more
      relaxed binding specificity than PAR proteins, in that they recognize many sites
      within promoter or randomly selected rat genomic DNA sequences that are ignored
      by PAR proteins. Thus, DNAse I protection experiments suggest that C/EBP
      recognizes a binding site with an affinity similar to the one of the cholesterol
      7 alpha hydroxylase gene promoter every 200 to 300 bp. The frequency of PAR
      protein binding sites with comparable affinities is about 20-fold lower in the
      rat genome. By using a PCR-based amplification assay we selected high affinity
      DNA-binding sites for C/EBP beta and the PAR protein DBP from a pool of
      oligonucleotides. Both proteins indeed recognize similar sequences with the
      optimal core binding sequences 5'RTTAY.GTAAY3'. However, as expected, DBP, is
      considerably less tolerant to deviations from the consensus site. Here we have
      characterized a single amino acid substitution mutant of C/EBP beta that
      increases its target site specificity. This protein, C/EBP beta V > A, contains a
      valine to alanine substitution at position 13 of the basic domain (residue 216 of
      C/EBP beta). C/EBP beta V > A selectively binds only the subset of C/EBP sites
      that are also DBP sites, both as oligonucleotides and within the natural contexts
      of the albumin and cholesterol hydroxylase promoters.

PMID- 8997491
TI  - Increased stability of phage T7g10 mRNA is mediated by either a 5'- or a 3'
      terminal stem-loop structure.
AB  - The mRNA encoding the major capsid protein of phage T7 (T7g10) is highly
      expressed in Escherichia coli. In common with other highly expressed T7 genes,
      the 5' end of this mRNA contains a stem-loop structure, while transcription
      termination at the phage T7 T phi terminator generates a stable 3'-end stem-loop
      structure. We assessed the influence of these structures on the expression level
      of T7g10 and on the functional stability of the mRNA. Each one of the 5'- or 3'
      hairpin structures was sufficient to increase the functional stability of the
      T7g10 mRNA more than twofold. A duplication of the 3' T phi-terminator slightly
      increased the mRNA stability further. Also, differences in the observed
      functional half-life could be correlated with the expression level of the T7g10
      derivatives when these were partially induced. Our data suggest that mRNA
      stabilization by a 5' stem-loop structure can occur even in the absence of a stem
      loop structure that protects RNA against 3' exonucleases.

PMID- 8997492
TI  - A muscarinic acetylcholine receptor, present in the epithelial cell line from
      Chironomus tentans.
AB  - A muscarinic cholinergic receptor (mAchR) is present in the non-neuronal
      epithelial cell line from Chironomus tentans. Scatchard plot analysis (KD = 1.4
      nM) using the non-selective antagonist quinuclidinylbenzilate (QNB), as well as
      kinetic data (KD = 1.7 nM), reveals one class of high affinity binding sites.
      About 2000 binding sites/cell are present. The receptor concentration (54.5 +/-
      7.5 fmol/mg protein) is comparable to the values reported from insect brain. The
      receptor interacts only with muscarinic ligands; nicotinergic acetylcholine
      receptors are not present. Binding properties are not comparable to any of the
      muscarinic subtypes known from vertebrate tissues. The rank order of competition
      of radiolabelled QNB is: QNB > atropine > PrBCM > oxotremorine, pirenzepine >
      methoctramine. The competition curve obtained with carbamylcholine is shifted to
      higher ligand concentrations in the presence of Gpp(NH)p and to lower
      carbamylcholine concentrations by 1 mM NEM. With antibodies against muscarinic
      receptor from calf brain one band with a molecular weight of about 80 kDa is
      detected on Western blots. The moulting hormone 20-OH-ecdysone transiently
      increases the concentration of muscarinic receptor.

PMID- 8997493
TI  - Purification of a new ribosome-inactivating protein from the seeds of Cinnamomum
      porrectum and characterization of the RNA N-glycosidase activity of the toxic
      protein.
AB  - Porrectin, a new type II ribosome-inactivating protein (RIP), was purified from
      the seeds of the camphor tree (Cinnamomum porrectum) by affinity chromatography
      on acid-treated Sepharose 4B. Porrectin is a glycoprotein (M(r)64,500, sugar
      content 2.5%) consisting of an A-chain (M(r)30,500) and a B-chain (M(r)33,500)
      linked by the disulfide bond. The terminal sugar of glycan in porrectin B-chain
      is determined to be mannose. By non-denaturing polyacrylamide gel
      electrophoresis, porrectin displayed three isoforms that have different pl values
      with the same molecular weight. Porrectin is a potent inhibitor of eukaryotic
      protein synthesis in the rabbit reticulocyte lysate system. The molecular
      mechanism of action of porrectin on rat liver ribosomes is demonstrated to be
      specific for RNA N-glycosidase. The cleavage site is the adenosine at position
      4324 (rat liver 28S rRNA) embedded in the highly conserved ricin/alpha-sarcin
      ('R/S') domain.

PMID- 8997495
TI  - Purification and characterisation of 6 and 58 kDa forms of the endogenous serine
      proteinase inhibitory proteins of ovine articular cartilage.
AB  - The major ovine articular cartilage (AC) serine proteinase inhibitory protein
      (SPI), a 58 kDa glycoprotein (SPI-58), was purified to homogeneity by sequential
      Sephacryl S-300 gel permeation, concanavalin A affinity, Mono Q anion exchange
      and Superose 12 FPLC. If precautions to prevent degradation of the native 58 kDa
      SPI were not undertaken during the early stages of its purification a SPI of
      approximately 6 kDa (SPI-6) was generated. SPI-6 could also be generated from SPI
      58 by chymotrypsin affinity chromatography, suggesting that SPI-6 could be
      produced from SPI-58 in vivo by proteolytic processing within the tissue. SPI-6
      was indistinguishable from the Kunitz inhibitor, bovine pancreatic trypsin
      inhibitor (BPTI) by SDS-PAGE under both reducing and non reducing conditions and
      showed a strong homology to BPTI in N-terminal sequence. These data suggest that
      the BPTI-like 6 kDa SPI constituted the inhibitory domain of the native 58 kDa
      SPI of ovine AC. Detection of [14C]-lysine-SPI-6 and SPI-58 in the serum free
      culture medium from ovine chondrocytes cultured in alginate beads in the presence
      of [14C]-lysine indicated that these SPIs were chondrocyte biosynthetic products.
      The inhibitory profiles of SPI-58 and SPI-6 differed somewhat suggesting that
      each may have an independent role in vivo.

PMID- 8997494
TI  - Structural determinants of putrescine uptake inhibition produced by cationic
      diamidines in the model of trypanosomatid Crithidia fasciculata.
AB  - The effect of a heterologous series of cationic diamidines has been tested on
      cell growth and polyamine uptake on the model of insect Trypanosomatid Crithidia
      fasciculata. The maximum inhibitory effect on both parameters was found for
      pentamidine and dibromopropamidine, which exhibit a longer distance between amino
      and imino substituents. A minimum inhibitory effect was found with amicarbalide.
      A good relationship was obtained when the distance between amino moieties was
      plotted versus the inhibitory effect on putrescine uptake, suggesting a role of
      this structural property on polyamine transport in Crithidia fasciculata. In
      addition, a similar correlation was obtained for another Trypanosomatid parasite,
      Leishmania infantum.

PMID- 8997496
TI  - Inhibition of the growth and cysteine proteinase activity of Porphyromonas
      gingivalis by human salivary cystatin S and chicken cystatin.
AB  - The mutual effects of P. gingivalis and several cystatin species has been
      investigated. After incubation with P. gingivalis culture supernatant, cystatin
      S, cystatin C and chicken cystatin were truncated from a 14 kDa protein into a
      polypeptide of approximately 13 kDa. Amino acid sequence analysis of the
      truncated cystatin S polypeptide revealed that cystatin S was cleaved after Arg
      8. All three types of truncated cystatins fully retained their inhibitory
      activity toward papain. Cystatin S and chicken cystatin partially inhibited
      proteolytic activity in the culture supernatant of P. gingivalis. Furthermore,
      cystatin S and chicken cystatin inhibited the growth of P. gingivalis in culture
      to 50% at approximately 1 microM.

PMID- 8997497
TI  - Dependence on intracellular pH and Mg2+ of metabolic compartmentation of
      phosphoinositides in human erythrocytes.
AB  - Effects of intracellular pH and Mg2+ on turnover and extent of metabolic
      compartmentation of phosphomonoester groups of phosphoinositides and
      phosphatidate were investigated in human erythrocytes by short-term and
      equilibrium labeling with [32P]Pi under steady-state conditions. At pH 6.7, the
      specific radio-activities of phosphoinositides reached apparent equilibrium
      values, in the range of 70% of that ATP-gamma-P after long-term labelling. At pH
      7.2, these values were in the range of 40-50% of that ATP-gamma-P. This
      demonstrates a decreased accessibility of phosphoinositides to enzymatic
      phosphorylation and dephosphorylation at the transition from acidic to normal
      incubation conditions. These changes were more pronounced at pH 7.8. High
      intracellular [Mg2+] initially activated the turnover of phosphoinositides at pH
      7.2. The activation changed into an inhibition and an increase of metabolic
      compartmentation after three hours preincubation of erythrocytes at high [Mg2+].
      The long-term Mg2+ effects are reversible to a great extent by a subsequent re
      reduction of [Mg2+]. In conclusion, deprotonation of phosphoinositides by low
      [H+] or high intracellular [Mg2+] at normal pH induces a decreased accessibility
      for their specific lipid kinases and phosphatases. This effect may be the result
      of lateral phase separation of acidic phospholipids as a consequence of divalent
      cation complexation under both experimental conditions, high pH and high [Mg2+]
      at normal pH.

PMID- 8997498
TI  - Disulfide bonds and free SH-group in pig kidney aminopeptidase P.
AB  - Pig kidney aminopeptidase P contains five cysteines. In the present report four
      of them are shown to be involved in disulfide bridges connecting Cys9 to Cys100
      and Cys267 to Cys272. The fifth cysteine, Cys58, could be carboxymethylated in
      the complete protein under denaturing conditions but without reduction indicating
      that the SH-group was free.

PMID- 8997499
TI  - Highly conserved structure in the promoter region of the gene for muscle-specific
      calpain, p94.
AB  - p94 belongs to the calcium-dependent cysteine protease (calpain) family which has
      been detected from human to mold. In contrast to the conventional m- and mu
      calpains which are expressed ubiquitously, expression of p94 predominates in
      skeletal muscle, and the mRNA for p94 is at least 10-times more abundant than
      mRNAs encoding in the m- and mu-types. The unique feature of p94 is that it
      undergoes rapid and exhaustive autolysis with a half-life of less than half an
      hour. To elucidate the nature of specific and abundant expression in skeletal
      muscle, and to proceed toward gene targeting p94, we have cloned and
      characterized mouse and rat genes for p94, and compared them with that of the
      human sequence. The sequence comparison among three mammalian species revealed
      several conserved regions including possible transcription factor binding sites.
      Furthermore, mouse and rat upstream regions of p94 are conserved over 3 kb
      suggesting that expression of p94 in skeletal muscle of both rodents is similarly
      regulated.

PMID- 8997500
TI  - The floor plate of the hindbrain is a highly specialized gland.
      Immunocytochemical and ultrastructural characteristics.
AB  - Although the participation of the floor plate (FP) in the differentiation of
      neurons in the ventral spinal cord is well established, the function of the FP at
      the level of the hindbrain is not known. The present investigation was focused on
      the FP of the rat hindbrain. We used an antibody specifically labeling the rat FP
      (FP4) and an antiserum raised against the secretory glycoproteins of the
      subcommissural organ that also reacts with an intracellular material in the FP.
      Immunocytochemical and ultrastructural evidence was obtained indicating that the
      rostralmost end of the FP, at the metencephalon, is a highly specialized gland
      which differentiates early and undergoes regression before birth. The material(s)
      secreted by these FP cells appear to be transported downward into their basal
      processes, and upward into ventricular protrusions. It is proposed that the
      former would participate in the differentiation of the serotonergic neurons, and
      the latter could be released into the ventricle and reach distant targets.
      Furthermore, evidence is presented supporting the occurrence of regional and
      temporal specializations of the FP.

PMID- 8997501
TI  - Vicia villosa agglutinin labels a subset of neurons coexpressing both the mu
      opioid receptor and parvalbumin in the developing rat subiculum.
AB  - Vicia villosa agglutinin (VVA), anti-parvalbumin antiserum and an affinity
      purified anti-mu opioid receptor antibody were used to triple-label neurons in
      the postnatal rat subiculum. VVA labeled a subset of mu opioid receptor-positive
      neurons that were also immunoreactive for parvalbumin. The morphology of the
      triple-labeled neurons was heterogeneous, and included multipolar, ovoid and
      pyramidal-shaped neurons. Neurons single-labeled for the mu opioid receptor, VVA
      or parvalbumin were also morphologically heterogeneous. The postnatal development
      of mu opioid receptor immunoreactivity (IR), parvalbumin-IR and VVA binding was
      investigated using triple-labeling immunocytochemistry. Mu opioid receptor-IR
      appeared first and was present at postnatal day 1 (P1). Parvalbumin-IR was first
      observed in somata at P10, followed by proximal and distal dendrites at P15 and
      P20 respectively. Faint VVA labeling was seen first at P10 and surrounded a
      limited number of neurons. The intensity of labeling and the number of neurons
      labeled with VVA increased between P10 and P20; however, both measures remained
      below adult levels at P20. This study further illustrates the neurochemical
      heterogeneity of interneurons in the hippocampal formation and shows the
      developmentally early appearance of mu opioid receptor-IR compared to the late
      appearance of VVA binding and parvalbumin-IR.

PMID- 8997502
TI  - Age-dependent effects of glutamate toxicity in the hippocampus.
AB  - While prolonged seizures can cause brain damage at any age, the extent of brain
      damage following prolonged seizures is highly age-dependent. Seizures in the
      immature brain are followed by far less histological damage than seizures of
      similar duration and intensity in mature animals. The reasons for this age
      related phenomenon are unclear. Seizure-induced cell death may be due to the
      neurotoxic effects of excessive glutamate release, we tested the hypothesis that
      the immature brain is less vulnerable to glutamate-induced neurotoxicity than the
      mature brain. We administered equal amounts of glutamate (0.5 mumol in 1.0
      microliter) unilaterally into the CA1 subfield of the hippocampus of rats at
      postnatal (P) days 10, 20, 30, and 60. Equal volumes of saline were injected in
      the contralateral hippocampus. Rats were killed 7 days later and their brains
      were examined for hippocampal cell loss. The size of the resultant hippocampal
      lesion was highly age-dependent. Minimal cell loss was noted in the P10 rats,
      lesions in the P20 rats were smaller than those at P30 and P60, which were
      similar in extent. This study demonstrates that the extent of glutamate
      neurotoxicity in the hippocampus is highly age-dependent, with immature
      hippocampi relatively resistant to glutamate-induced cell death.

PMID- 8997503
TI  - Isolation of cDNA clones of the rat mRNAs expressed preferentially in the
      prenatal stages of brain development.
AB  - For better understanding of the molecular mechanisms underlying the developmental
      processes of the mammalian brain, we isolated rat fetal brain-enriched (FBE) cDNA
      clones, whose corresponding mRNAs were expressed at least 5-fold more in the
      fetal brain than in the adult brain. Our modified differential screening
      procedure, which utilized a two-vector (pT7T3D and pBluescript) system and showed
      low background levels of colony hybridization for screening, efficiently
      identified 64 candidate FBE clones from a small number (475) of colonies in the
      fetal brain cDNA library. After subsequent second screening of the candidate FBE
      clones by Northern blot analysis, we successfully isolated 22 distinct FBE
      clones. The nucleotide sequence analysis of the 22 FBE clones revealed that 13 of
      them had no significant matches to the sequences reported in the databases,
      whereas 9 of them matched previously reported sequences (alpha-tubulin M alpha 1,
      beta-tubulin M beta 5, thymosin-beta 10, stathmin, beta-tubulin M beta 2, alpha
      internexin, ferritin Lg chain, neuronatin and amphoterin), most of which have
      been shown to be down-regulated during brain development. We also found that the
      Northern blot analysis in the second screening could be replaced by cDNA library
      DNA-Southern blot analysis, in most clones corresponding to relatively abundantly
      expressed mRNAs. Thus, once the cDNA library is constructed, clone selection will
      be possible in such clones without the use of additional RNA or Northern blot in
      screening, allowing the analysis of small brain regions of interest.

PMID- 8997504
TI  - Vulnerability of CA1 neurons to glutamate is developmentally regulated.
AB  - Although it is well documented that glutamate receptor subtypes are
      differentially expressed during central nervous system development postnatally,
      how glutamate affects neurons during postnatal development is unclear. We
      therefore examined the development of the intrinsic neuronal response to
      glutamate receptor activation by studying single, hippocampal CA1 neurons that
      had been acutely dissociated from newborn (P1-3), 1 week old (P6-8), and 3 week
      old (P21-25) rats. Using laser scanning confocal microscopy and the calcium dye
      Fluo-3, we made time-lapse studies of the effects of glutamate stimulation on
      free intracellular calcium ([Ca2+]i) and simultaneous changes in neuronal
      morphology. In P21-25 neurons, glutamate increased [Ca2+]i fluorescence, and
      caused marked somal swelling, blebbing, and retraction of dendrites into the
      soma. These major morphological changes were followed by sudden loss of
      intracellular fluorescence, indicative of a loss of membrane integrity and cell
      death. In P6-8 neurons, glutamate increased [Ca2+]i to the same extent, but this
      increase was not followed by either major morphological changes or loss of
      membrane integrity. In P1-3 neurons, glutamate increased [Ca2+]i minimally, and
      no morphologic changes were observed. P1-3 neurons dissociated without enzymatic
      digestion demonstrated glutamate responses identical to responses seen in neurons
      dissociated with enzymatic digestion. In the presence of MK-801 (15 microM),
      glutamate still increased [Ca2+]i and caused cell death in P21-25 neurons, but
      the latency to these effects more than tripled. This late, MK-801-resistant
      [Ca2+]i increase was not eliminated by DNQX or Ni2+/Cd2+, suggesting that this
      increase is mediated by metabotropic receptors. These findings demonstrate that
      (1) hippocampal neurons from newborns are intrinsically less vulnerable to
      glutamate toxicity than neurons from 3 weeks old animals, and (2) multiple
      glutamate receptor subtypes affect the magnitude of the [Ca2+]i increase in
      response to glutamate in the neuronal microenvironment.

PMID- 8997505
TI  - Prenatal nicotine effects on memory in rats: pharmacological and behavioral
      challenges.
AB  - Cigarette smoking during pregnancy has been shown in a variety of studies to be
      associated with cognitive deficits in the children. Nicotine administration to
      rats during gestation has been found to cause subtle cognitive effects in the
      offspring. Some individual differences in cognitive impairment may be related to
      prenatal nicotine effects on noradrenergic (NE) systems. In the current study, 10
      Sprague-Dawley rat dams were infused with approximately 2 mg/kg/day of nicotine
      ditartrate via osmotic minipumps and 10 control dams were exposed to vehicle
      containing minipumps from gestational day (GD) 4-20. Starting on postnatal day
      (PND) 50, the offspring were tested for T-maze rewarded spatial alternation with
      intertrial intervals of 0, 10, 20, or 40 s. There was a sex- and delay-dependent
      effect of prenatal nicotine exposure on T-maze alternation. Nicotine-exposed
      males showed a significant deficit at the 0 s delay. In radial-arm maze (RAM)
      acquisition training there were no significant nicotine effects. However,
      significant nicotine-related effects were seen with subsequent behavioral and
      pharmacological challenges in the RAM. Changing the RAM testing location to an
      identical maze in a different room elicited a significant choice accuracy deficit
      in the prenatal nicotine-exposed rats compared with controls. Acute nicotine
      challenge did not cause any differential effects in the prenatal nicotine and
      control groups. During the isoproterenol (beta-NE agonist) challenge phase there
      appeared a significant facilitation of choice accuracy and speeding of response
      in the prenatal nicotine exposure group which was not seen in the control group.
      The alpha-NE agonist phenylpropanolamine caused a significant deficit in control
      females but not in the females prenatally exposed to nicotine. No differential
      effects of the alpha-NE antagonist phenoxybenzamine were seen in the prenatal
      nicotine and control groups. Throughout RAM testing there was a significant sex
      effect with males having better choice accuracy than females. These results
      demonstrate that the persisting cognitive effects of prenatal exposure to 2
      mg/kg/day cause subtle effects in cognitive performance which can be elicited
      with behavioral and pharmacological challenge. These results also support
      previous studies suggesting the involvement of NE systems in persisting effects
      of prenatal nicotine exposure.

PMID- 8997506
TI  - GABAA receptor subunit expression and assembly in cultured rat cerebellar granule
      neurons.
AB  - The assembly of multisubunit GABAA receptors in specific neuronal populations is
      a complex process which is poorly understood. To begin to examine receptor
      assembly, alpha 1, beta 2/3, and gamma 2 subunit polypeptide expression and
      association, as well as receptor binding, were examined in cultured rat
      cerebellar granule neurons. Western blots revealed two alpha 1-immunoreactive
      proteins. A 39 kDa species was maximal at 2 days in culture and subsequently
      declined. In contrast, a 51 kDa polypeptide, the anticipated size of the mature
      alpha 1 subunit, was first detected at 4 days and increased throughout the
      culture period. Additional studies demonstrated that the beta 2/3 and gamma 2
      subunits were detectable at 2 days and attained maximal levels by 6 days. The
      level of [3H]Ro15-1788 binding, a measure of assembled receptors, rose in
      parallel with the increases in the 51 kDa alpha 1, beta 2/3 and gamma 2 subunits.
      Moreover, the 51 kDa alpha 1, beta 2/3, and gamma 2 subunits were associated in
      receptor complexes. However, immunohistochemical studies demonstrated the
      presence of substantial intracellular subunit staining. This finding suggest that
      only some of the subunits expressed in granule neurons contribute to functional
      GABAA receptors on the cell surface.

PMID- 8997507
TI  - The alpha 1 subunit of soluble guanylyl cyclase is expressed prenatally in the
      rat brain.
AB  - The mRNA encoding the alpha 1 subunit of soluble guanylyl cyclase (alpha 1sGC)
      was identified in a different-display screening for genes spatially and
      temporally regulated during the development of fetal rat brain. The initially
      isolated fragment of the 3' untranslated region was used for in situ
      hybridization and to produce full-length cDNA clones by hybridization screening
      of cDNA libraries and by RACE (rapid amplification of cDNA ends), respectively.
      In situ hybridization analysis that alpha 1sGC was absent at embryonic day 12
      (E12), but by E14-E15, the forebrain exhibited dense expression in the developing
      striatum, medial cerebral wall containing the presumptive hippocampus, cerebellar
      neuroepithelium, and roof plate. Weaker expression was observed in the septum,
      epithalamus, ventral thalamus, pineal gland and retina. This pattern is largely
      maintained and refined at E18, with additional expression domains in the
      olfactory tubercle, nucleus accumbens, zona incerta and neocortex. During early
      postnatal development, the adult pattern is expressed, as previously reported.
      The unexpected, early expression of alpha 1sGC, in conjunction with the known
      absence of its heterodimeric partner, the beta subunit of sGC, from the
      developing rodent brain during fetal ages raises potentially novel functional
      roles of the alpha 1 subunit during ontogeny, and might imply the existence of an
      alternative beta subunit specific for the prenatal brain.

PMID- 8997508
TI  - Beta 1 integrins regulate axon outgrowth and glial cell spreading on a glial
      derived extracellular matrix during development and regeneration.
AB  - In the present study we have investigated functional roles for beta 1 integrin
      receptors in regulating axon outgrowth, and glial cell adhesion and spreading in
      the Xenopus retina. The XR1 glial cell line, isolated from Xenopus retinal
      neuroepithelium, deposits a proteinaceous extracellular matrix (ECM) with potent
      neurite outgrowth promoting activity. To investigate a potential role of the
      integrins as cellular receptors for these glial cell-derived ECM components,
      embryonic and regenerating retinal explants were cultured in the presence of
      polyclonal antibodies directed against the beta 1 integrin receptor complex. The
      IgGs and Fabs of the anti-beta 1 integrin antibody strongly inhibited ganglion
      cell axon outgrowth on the glial cell-derived ECM, although axons grew freely
      across the surfaces of glial cells surrounding the explants. The antibodies also
      inhibited outgrowth on purified laminin containing substrates in a dose-dependent
      fashion. In addition, the anti-beta 1 antibodies were effective at inhibiting the
      spreading of glial cells that migrated out from the embryonic explants, and also
      inhibited attachment and spreading of Xenopus XR1 glial cells on ECM substrates.
      These results show that the beta 1 integrins play important functional roles in
      axon outgrowth during development and regeneration, and also serve in regulating
      retinal glial cell attachment and spreading in vitro, and thus are likely to play
      similar roles in vivo.

PMID- 8997509
TI  - Comigration of tyrosine hydroxylase- and gonadotropin-releasing hormone
      immunoreactive neurons in the nasal area of human embryos.
AB  - Tyrosine hydroxylase (TH) immunoreactive (IR) central catecholaminergic neurons
      have been observed in human CNS from 4.5 gestational weeks (g.w.) on [Verney, C.,
      Zecevic, N. and Puelles, L. Eur. J. Neurosci., Suppl. 8 (1995) 7044; Zecevic, N.
      and Verney, C., J. Comp, Neurol., 351 (1995) 509-535]. We describe here a
      discrete TH-IR cell population localized in the rostral nasal region during
      embryonic development. Tyrosine hydroxylase-IR cells spread from the olfactory
      placode towards the basal and medial telencephalon. They follow the same
      migration path as the gonadotropin-releasing hormone (GnRH)-IR hypothalamic
      neurons. Tyrosine hydroxylase-IR neurons are first detected at 4.5 g.w., while
      GnRH-IR cells are visualized later at 5.5 g.w. Double immunocytochemical labeling
      reveals the presence of three neuronal populations comigrating along the
      developing vomeronasal-nervus terminalis complex. These populations express
      either one or both TH and GnRH phenotypes depending on their position in the
      migration route. At 6 g.w., most of the neurons express TH immunoreactivity as
      they leave the vomeronasal organ whereas most of the GnRH-IR neurons are detected
      closer to the CNS and in the CNS itself. These results emphasize the early
      phenotypic heterogeneity of the different migrating neuronal populations
      generated in the olfactory placode in humans. At later stages, very few TH-IR
      neurons are detected in the anterior forebrain suggesting a transient expression
      of TH immunoreactivity within these neuronal populations.

PMID- 8997510
TI  - Age-related changes in calcitonin gene-related peptide and substance P in renal
      afferent nerve soma in the rat. Association with afferent renal nerve activity.
AB  - Renal afferent neurons were retrogradely labeled with FluoroGold in Sprague
      Dawley rats at 50, 60, 70, 80, 90, 110, 130 and 200 days of age. Recordings of
      afferent renal nerve activity (ARNA) and immunofluorescent assessment of
      calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and substance P
      (SP)-LI in spinal ganglia T10-L1 were obtained in the same rats. The frequency of
      renal afferent neurons positive for CGRP-LI declined abruptly from 88% in animals
      younger than 100 days of age (342 of 388 total cells) to 63% in rats older than
      100 days of age (223 of the 353 total cells). The intensity of CGRP-LI (scaled 1
      3) in renal afferent CGRP-positive neurons also declined significantly from a
      mean of 2.23 +/- 0.04 before 100 days to 1.48 +/- 0.05 in older rats (P < 0.001
      in each age group). SP-LI positive neurons declined from 44% to 28% (P < 0.001).
      These changes in neuropeptide immunofluorescence coincided with an altered
      pattern of ARNA in which the excitatory response to complete renal ischemia
      increased from 274 +/- 69% above background to 1167 +/- 124% after the age of 100
      days. Previous studies have shown that this alteration in the ARNA response to
      renal ischemia is due to the appearance of activity from R1 chemoreceptor nerves
      in ARNA. These data demonstrated that this transition in the electrophysiologic
      characteristics of ARNA is accompanied by profound alterations in CGRP-LI and SP
      LI levels in renal afferent nerve cell bodies.

PMID- 8997511
TI  - Presence of somatostatin sst2 receptors in the developing rat auditory system.
AB  - A transient expression of somatostatin mRNA as well as of the peptide itself has
      been described in the developing mammalian auditory brainstem. However, little is
      known about the presence, and the spatial and temporal pattern of somatostatin
      (SRIF) receptor subtypes in this system. Therefore, we investigated the
      distribution of SRIF receptor binding sites labeled with the radioligands
      [125I]LTT-SRIF-28, [125I]Tyr3-octreotide, and [125I]CGP 23996 (in buffers
      containing either Mg2+ or Na+ ions) within the developing auditory brainstem of
      the rat. In addition, we performed in situ hybridization with a 35P-labeled
      oligoprobe, specific for somatostatin sst2 receptor mRNA. We observed a transient
      expression of SRIF receptors, labeled with [125I]LTT-SRIF-28, [125I]Try3
      octreotide, and [125I]CGP 23996 (only in the presence of Mg2+ ions), in all
      principal auditory nuclei during neonatal development. In the adult rats,
      however, only the inferior colliculus displayed significant SRIF receptor
      binding. A very similar spatiotemporal labeling pattern was found for sst2
      receptor mRNA. Our in situ hybridization data, together with those on ligand
      binding, suggest a predominantly transient expression of sst2 receptors in the
      auditory system. Since sst2 sites (and possibly sst3 and sst5) as well as SRIF
      itself appear to be co-expressed during a period when synapse maturation occurs,
      we suggest that sst2 receptors are involved in this process of the developing
      auditory system.

PMID- 8997512
TI  - Apoptosis in the cerebellum of adult teleost fish, Apteronotus leptorhynchus.
AB  - While involvement of programmed cell death (apoptosis) in embryogenesis is well
      established, only very little is known about this phenomenon in later stages of
      development. Based primarily on indirect evidence, it has been proposed that
      during postembryonic development of fish cell death does not occur. We have re
      addressed this issue by examining the gymnotiform fish Apteronotus leptorhynchus.
      This teleost exhibits a high degree of proliferative activity in the brain during
      adulthood. Most of these cells are born in the cerebellum, where they
      differentiate, migrate into specific target regions, and are added to the
      population of already existing cerebellar cells. By applying morphological
      criteria and an in situ technique for the detection of DNA fragmentation (a
      feature characteristic of apoptotic cells), we show here that a large number of
      cerebellar cells undergo apoptosis. The density of apoptotic cells is
      significantly higher in the granule cell layers of the subdivisions of the
      cerebellum than in the corresponding molecular layers. This finding is consistent
      with previous observations indicating a drastic reduction in areal density of
      newborn cells within these granule cell layers in a period 4-7 weeks after their
      generation. In the granule cell layers of two cerebellar subdivisions, the corpus
      cerebelli and the valvula cerebelli pars medialis, the areal density of apoptotic
      cells displays a significant negative correlation with body weight, thus pointing
      to a decrease in the number of apoptotic events with age. The results of our
      investigation provide clear evidence for the existence of apoptosis during
      adulthood in fish and underline the significance of this process in the
      postembryonic development of the brain.

PMID- 8997513
TI  - Migration of neurons containing gonadotropin releasing hormone (GnRH) in slices
      from embryonic nasal compartment and forebrain.
AB  - During development, neurons containing gonadotropin-releasing hormone traverse
      fiber bundles in the nose, cross into the brain, and move through a maze of glial
      and axonal fibers. To test whether GnRH neurons utilize cues intrinsic to their
      migration route to traverse the nasal/brain boundary, tissue slices that maintain
      connections between the forebrain and nasal compartment were prepared from mouse
      embryos. Cell migration between the nasal and brain compartments was evident
      based on changes in cell positions after successive days in vitro.

PMID- 8997514
TI  - Development of astrocytes and neurons in cultured brain slices from mice lacking
      connexin43.
AB  - Astrocyte and neuronal development was investigated in organotypic brain slice
      cultures from mouse fetuses with a null mutation in the connexin43 gene.
      Astrocyte morphology and electrical properties were indistinguishable in null
      mutant slices and control slices but at 18 days in vitro astrocyte density in the
      central regions of the null mutant slices was significantly higher than in
      control slices. Neuronal development assessed morphologically and
      electrophysiologically appeared normal in the mutant slices. These results
      suggest that intercellular communication mediated through connexin43 is not
      essential for the development of astrocytes and neurons but may play a role in
      regulating astrocytic migration.

PMID- 8997515
TI  - The BDNF content of postnatal and adult rat brain: the effects of 6
      hydroxydopamine lesions in adult brain.
AB  - Brain-derived neurotrophic factor (BDNF) has been well studied for its effects in
      improving survival and differentiation of the central and peripheral nervous
      system. In order to understand the developing CNS and the pathogenesis of brain
      injury, an enzyme immunoassay was employed to detect BDNF protein in the various
      tissues of developing and adult animals. Increased levels of the BDNF were found
      in the hippocampus, cerebrocortex, striatum, cerebellum and ventral mesencephalon
      in 2-week-old rats, compared with that in postnatal day 0 pups. In the adult rat,
      the highest level of BDNF was detected in the hippocampus (14.5 +/- 0.8 ng/g wet
      tissue), with a relatively high level also observed in the cerebrocortex and
      striatum. In peripheral tissues, a substantial amount of BDNF protein was
      observed in various organs. The changes in BDNF levels in the striatum and the
      ventral mesencephalon of unilaterally 6-hydroxydopamine-lesioned young adult rats
      were also examined. Significant increases of BDNF levels were detected during 2
      weeks after lesion.

PMID- 8997516
TI  - Bindings of metallothionein to supranucleosomal fibers in mouse pancreatic nuclei
      after induction by 4-aminopyrazolo [3,4-D] pyrimidine.
AB  - To examine intranuclear localization of metallothionein (MT) induced by
      administration of 4-aminopyrazolo [3,4-d] pyrimidine (4-APP), the present study
      of MT was performed by immuno-electron microscopy. One day after oral
      administration of 4-APP, the mouse pancreas removed and frozen with dry ice was
      cut at about 1 mm thickness. Pancreatic slices were reacted with anti-MT
      antibody, fixed with formaldehyde and glutaraldehyde, and embedded in hydrophilic
      Lowicryl K4M resin. Ultrathin sections were reacted with the secondary antibody
      labelled with colloidal gold, and stained both with uranyl acetate and with lead
      citrate. It was found that the MT site was shown simultaneously in the chromatin
      and in the rough endoplasmic reticulum of mouse pancreatic exocrine cells one day
      after administration of 4-APP. The structure of MT-binding chromatin was composed
      of supranucleosomal fibers, but not of nucleosomal fibers.

PMID- 8997517
TI  - Genomic alterations in human prostate carcinoma cell lines by two-dimensional gel
      analysis.
AB  - To explore the molecular abnormalities in human prostate carcinoma, the genomic
      DNAs extracted from 3 prostate cell lines--LNCaP, PC-3 and DU-145--were examined
      using restriction landmark genomic scanning (RLGS) methodology, a 2-dimensional
      gel analysis which allows evaluation of approximately 2,000 Not I landmarks. We
      detected 24, 18 and 23 amplified spots in LNCaP, PC-3 and DU-145, respectively.
      Eleven spots were commonly intensified in all 3 cell lines, with a range of
      amplification of 2.1 to 134.1-fold over normal. An additional 4 spots were
      detected in both LNCaP and Pc-3 at similar amplification intensities, but were
      not observed in DNA from DU-145. Ten amplified spots were located on several
      chromosomes, while other five spots seemed to result from the hypomethylation.
      These results suggest that common genetic abnormalities may occur in carcinomas
      of the human prostate.

PMID- 8997518
TI  - Immunocytochemical study of uptake of exogenous carrier-free copper-zinc
      superoxide dismutase by peripheral blood lymphocytes.
AB  - We recently demonstrated that exogenous copper-zinc superoxide dismutase (SOD)
      reduced HIV replication in tumor necrosis factor alpha activated chronically HIV
      infected promonocytic U1 cell line and in peripheral blood mononuclear cells
      coculture. However, whether exogenous SOD penetrates the cellular membrane or
      acts extracellularly has been remained controversial. SOD has been considered as
      not to penetrate the cellular membrane because of its high molecular weight, thus
      the main site of action is presumed to be extracellular. In order to determine
      whether exogenous SOD penetrates inside the cell, we utilized a gentle
      immunocytochemical method to detect Mn and Cu,Zn SOD in peripheral blood
      lymphocytes incubated with various concentrations of exogenous carrier-free Cu,Zn
      SOD without prior permeabilization of cell membranes. After 24 hrs. the total SOD
      activity and immunocytochemical studies were performed. Here we demonstrate
      clearly that a large amount of carrier-free Cu,Zn SOD, added exogenously,
      penetrates the cellular membrane and increases total SOD activity.

PMID- 8997519
TI  - Bowel resection and neurotensin treatment. Histochemical study of neurotensin
      like and somatostatin-like immunoreactivities and receptors.
AB  - The influence of a bowel-trophic neurotensin (NT) treatment (13 days, 300
      micrograms/kg/every 12 hrs.) on neurotensin-like immunopositive structures
      (neurons, fibres and epithelial-N-cells) and the neurotensin receptors (NTr) in
      the residual bowel after resection (90% small bowel or 75% colon) in the rat was
      studied using histochemical methods. Somatostatin-like (ST) immunopositive
      structures (neurons, fibres and epithelial-D-cells) and somatostatin receptors
      (STr) were also studied, comparatively. The results displayed a general increase
      of N-cells (11-17%) but not of D-cells, and a higher degree of variability
      section-to-section in the NT and ST immunopositive nervous structures (without
      increased density) after both resections, both with or without NT treatment.
      Receptors did not change after the small bowel resection but the colon resection
      and/or the NT treatment produced variations in the NT binding (from -24.3 to
      +16.85) in different intestinal regions. In a general sense, the variations among
      1) the controls, 2) the resected animals, and 3) the resected and NT-treated
      animals, were of less extent (< or = 24%) than previously supposed for explaining
      the trophic effect of NT. Our results: a) confirm the autonomy, injury-resistance
      and tendency to maintain the physiological features of the bowel in very diverse
      situations; b) open new questions on both, the neurotensinergic changes after
      bowel resection and the mechanisms of the trophic effect of NT treatment, and c)
      suggest that, when neurotensin was applied as a trophic treatment in the cases of
      the need of a bowel resection, no important neurotensinergic or somatostatinergic
      side effects should be expected in the remaining bowel. However, the higher
      degree of variability section-to-section after surgery in the nervous structures
      was not modified by the NT treatment. This fact, and the different response of
      various intestinal regions to the NT treatment, suggest that functional problems
      in the remaining bowel could be maintained despite the growth of the mucosa
      induced by the NT treatment.

PMID- 8997520
TI  - The 5' part of the human H19 RNA contains cis-acting elements hampering its
      translatability.
AB  - H19 is an imprinted gene developmentally regulated in man and mouse and
      implicated in various neoplasms. No corresponding protein product has yet been
      detected, although several open reading frames (ORFs) could be identified along
      its RNA. The largest ORF found in the human gene could encode a putative 26 kDa
      protein. We have isolated two H19 cDNAs (AP and ES) that contain this ORF4 and
      correspond to incomplete copies of the unique 2.3 kb H19 RNA. In transient
      expression assays, AP was able to synthesize a 26 kDa protein whereas ES was not.
      With respect to ORF4, ES exhibits a 536 bp long GC-rich 5' untranslated region,
      whereas AP contains the last 22 nucleotides of this 5'UTR. Using deletions and
      point mutations, we have found that the length and probably the secondary
      structure of the 5'UTR strongly hampers the translatability of the RNA. In
      addition, a potential role of upstream ORFs (uORFs) was detected as stressed by
      the enhances translation of a construct mutated in uORF3 overlapping ORF4.
      Interactions between H19 and proteins are indicated by a specific binding between
      5'UTR derived RNA segments and two nuclear proteins of about 27 kDa. Our results
      favor a potential role of these particular structures and binding properties in
      general trans-regulation of RNA post-transcriptional processes rather than in
      normal control of H19 mRNA translation.

PMID- 8997521
TI  - Characterization of human platelet receptors for atrial natriuretic peptide:
      evidence for clearance receptors.
AB  - Characterization of human platelet receptors for atrial natriuretic peptide (ANP)
      has been performed using two different methods. First, intracellular cGMP levels
      were measured after platelet stimulation with humanANP (hANP) and CNP, in order
      to detect the presence of ANP-A or ANP-B receptors. The intracellular cGMP
      content was not modified either after hANP or CNP platelet stimulation and thus
      indicated the lack of biological active receptors on these cells. Second,
      displacements of 125I-hANP were similar when induced by hANP or C4-23ANP
      (specific ligand of clearance receptor). Consequently, these results confirmed
      that human platelet membranes bore only clearance receptors for atrial
      natriuretic peptide.

PMID- 8997522
TI  - 3D resolved two-photon fluorescence microscopy of living cells using a modified
      confocal laser scanning microscope.
AB  - Non-linear 3D imaging of fluorophore-labelled vital cells has been performed by
      femtosecond near infrared (NIR) microscopy. Ultraviolet and visible transitions
      of intracellular fluorophores, such as Fura-2, Calcium Green, Rhodamine 123 and
      fluorescent microspheres, were excited via simultaneous absorption of two 780 nm
      photons provided by a tunable Ti:Sapphire laser. The femtosecond laser was
      coupled to a conventional upright Zeiss confocal laser scanning microscope
      expanding its one-photon capabilities to 3D resolved two-photon microscopy.
      Pinhole-free non-linear 3D imaging was possible with 400 nm lateral and
      approximately 1 micron axial resolution. Axial resolution could be further
      improved by using an additional detection pinhole. The NIR average power and
      pulse width at the sample were adjusted to be 1-4 m W and 150-200 fs,
      respectively. Higher power levels resulted in cell damage as demonstrated by
      photoinduced lysis of human erythrocytes. The powerful capabilities of this
      universal microscope were demonstrated by 3D imaging of two-photon excited
      fluorophore-labelled macrophages during phagocytosis of fluorescent microsized
      beads.

PMID- 8997523
TI  - The response of goat brain cells to infection by caprine arthritis-encephalitis
      virus.
AB  - Caprine arthritis-encephalitis virus is a lentivirus of goats causing
      encephalomyelopathy acutely in young goats and occasionally in late stages of
      chronically infected adult goats. To determine the specific brain cells infected
      by the virus and the response of other cell types, goat cerebrum explant cultures
      prepared from newborn goat kids were infected by virus application. Infection of
      brain cultures was also possible by coculture with virus-infected macrophages.
      Predominantly, microglia cells were specifically infected by the virus, resulting
      in death of more than 50% of the cells within 2 weeks of infection. Infected
      cells enlarged and formed multinucleated giant cells. Infection of
      oligodendrocytes was observed, but infrequently. Astrocytes were not infected.
      Proviral deoxyribonucleic acid (DNA) was detected in infected cultures by
      amplification of a 490 base-pair fragment of the viral gag gene by the polymerase
      chain reaction (PCR) technique. Virus budding from plasma membrane of infected
      microglia cells was demonstrated by transmission electron microscopy. The
      supernatant of infected brain cells induced cytopathic effect when applied to
      indicator cells. These observations suggest productive infection of brain
      cultures. Virus infection of neurons was not observed. Culture of neurons in
      virus-free supernatant of CAEV-infected microglia or mixed glia culture resulted
      in death of 50% of the neurons in 11 days, suggesting the production of
      neurotoxic substances by the virus-infected glial cells.

PMID- 8997524
TI  - Involvement of the extracellular calcium in the release of elastase and the human
      neutrophils oxidative burst.
AB  - Some proteases (particularly elastase) and metabolites of very reactive oxygen
      species (superoxide anion, hydrogen peroxide, hypochlorous acid and hydroxyl
      radicals) are generated by polymorphonuclear neutrophils (PMNs) during
      inflammatory disorders. Divalent cations, especially calcium (Ca2+) play an
      important regulatory role in the different PMNs functions. The aim of this study
      is to determine the role of extracellular calcium during the liberation of
      elastase and of reactive oxygen species production by human PMNs. Consequently,
      in order to stimulate PMNs, phorbolmyristate acetate (PMA), formyl-methionyl
      leucyl-phenylalanine (fMLP) and opsonized zymosan (OZ) have been used. PMNs
      stimulated by OZ did not release elastase to reverse the PMA and fMLP systems.
      The production of elastase by PMNs stimulated by PMA to reverse the fMLP system
      is independent from the extracellular calcium, between 0.0 and 1.5 mM. With
      various higher concentrations of calcium, varying from 1.5 to 4.0 mM, the release
      of elastase by PMNs stimulated by PMA is extracellular calcium-dependent to
      reverse the fMLP system. The superoxide anion (O2-) generated by PMNs activated
      by fMLP is dependent from the extracellular calcium in the medium, whereas O2-
      production by PMA or OZ stimulated neutrophils was extracellular calcium
      independent. These observations suggest that an influx of calcium may play an
      important role in the production of elastase and in the capacity of PMNs
      stimulated by fMLP to produce O2- to reverse the PMA and OZ systems.

PMID- 8997525
TI  - Low sample volume causes differentiation in human rhabdomyosarcoma cell line RD
      subjected to electroporation.
AB  - Gene transfection has been accomplished with a variety of techniques such as DEAE
      dextran, calcium phosphate coprecipitation, protoplast fusion, liposomes,
      microinjection and recombinant bacteriophages. However, transfection by
      electroporation, consisting of the reversible permeabilization of cell membranes
      after exposure to a pulsed electric field, has been shown to be the most rapid,
      simple and efficient method for the stable incorporation of genes in different
      cell lines. We studied rhabdomyosarcoma cells subjected to electroporation in two
      different vol. [400 microliters (group 1) and 150 microliters (group 2] of 140 mM
      NaCl/15 mM Hepes buffer, pH 7.2) and evaluated the effects of electroporation
      volume on growth and differentiation. Low sample volumes induced a terminal
      process of morphological and ultrastructural myogenic differentiation in
      rhabdomyosarcoma cells, which concluded with cell death. Our results suggest that
      in electroporation low sample vol. of rhabdomyosarcoma cells induced
      morphological and phenotypic differentiation, with increased expression of
      desmin, alpha-actinin and tropomyosin.

PMID- 8997526
TI  - Non-specific pinocytosis by human endothelial cells cultured as multicellular
      aggregates: uptake of lucifer yellow and horse radish peroxidase.
AB  - We have analyzed the pattern of time-dependent and concentration-dependent
      incorporation of Lucifer Yellow CH (LY) and Horseradish Peroxidase (HRP) by human
      umbilical vein endothelial cells cultured on a non-adhesive substratum, where
      they they become organized into stable, multicellular aggregates. The data were
      compared with those previously obtained from low-density cultures of non-growing
      endothelial cells adherent to plastic. While the linear trend of the
      incorporation kinetics is preserved, the rate of uptake with both time and
      concentrations is highly dependent on the culture conditions, namely typology of
      cell-cell and cell-substrate interactions. An at least two-fold increase of the
      rate of uptake was observed with both markers in the aggregated cells. The
      extracellular concentration of LY required to saturate the binding capacity of
      the cell surface shifts from approximately 0.25 mg/ml, with the adherent cells,
      to approximately 0.5 mg/ml in the aggregated cells; the rate of uptake of three
      different forms of HRP shows, besides a sharp quantitative increase, also
      qualitative variations, testified by differential changes of their incorporation
      rates. These results are entirely consistent with the assumption that the
      association of the endothelial cells into multicellular aggregates increases the
      rate of pinocytic uptake by modifying the physicochemical properties of the cell
      surface, thereby increasing its differential affinity for the extracellular
      markers.

PMID- 8997528
TI  - Laboratory virology--diagnostic or testing service?

PMID- 8997527
TI  - Endothelin binding to NG108-15 cells: evidence for conventional ETA and ETB
      receptor subtypes and super-high affinity binding components.
AB  - The endothelin (ET) peptides have been identified in the CNS, but there is a
      paucity of information on their physiological roles. NG108-15 cells, a clonal
      strain of a neuroblastoma x glioma hybrid cell line, have been widely used in
      neurobiological research since they retain certain differentiated properties of
      the non-transformed parental cells. It is known that NG108-15 cells respond to
      the ET peptides, but only limited information is available on the
      characterization of the ET receptors that mediate these effects. The present
      study was designed to identify the type(s) of ET receptors on NG108-15 cells in a
      proliferative state by competitive binding assays using [125I]ET-1 as the
      radiolabelled ligand and the receptor-selective ligands. ET-1, ET-3, BQ-123,
      sarafatoxin-6-c and [Ala1,3,11,15]ET-1. The results suggested the presence of
      conventional ETA and ETB receptor subtypes, with ETA in excess over ETB. These
      findings were consistent with the results of Northern analysis in that mRNAs
      encoding the ETA and ETB receptor subtypes were identified in NG108-15 cells,
      with a preponderance of ETA to ETB. Of considerable interest was the observation
      of other ET-binding components with much higher affinities than the conventional
      receptors. It remains to be demonstrated if these particular binding components
      are functional and represent differ gene products or arise from association of
      the conventional ETA and ETB receptor subtypes with themselves or other
      structures, e.g. proteins or lipids, of CNS origin.

PMID- 8997529
TI  - Community social alarm network in Slovenia.
AB  - The article deals with a case report on the technology transfer of the Lifeline
      community social alarm system to Slovenia. The main reason the project was
      initiated is the ageing of the Slovenian population (11% of the population is 65
      or over). With this system we intend to support the public's wish to allow the
      elderly to remain in their own homes for as long as possible instead of placing
      them in institutional care. Between 1992 and 1995 the following results were
      achieved: the acceptability of the system in the social environment was
      increased; a pilot control centre in Ljubljana was established and has been
      operational for two-and-a-half years; a national dissemination plan was prepared;
      the integration of the programme into other information systems has been started.
      One of the main conclusions is that for the successful transfer of a technology
      which also affects social values in society, a social innovation must support the
      process.

PMID- 8997530
TI  - Pattern of inhalation exposure: blood levels and acute subnarcotic effects of
      toluene and acetone in rats.
AB  - Solvent blood concentrations and subnarcotic effects (inhibition of electrically
      evoked seizures) were measured in rats exposed to constant or fluctuating air
      concentrations of toluene or acetone. A 4 hour exposure of resting rats to
      toluene at an air concentration of 1 and 2 mg/l, or to acetone at 4 and 10 mg/l,
      led to blood levels of 6.7 and 12.8 mg/l of toluene, or 183 and 520 mg/l of
      acetone: seizure inhibition amounted to 18% and 40+, or 10% and 50%,
      respectively. Blood level and effect attained 1/2 of the final values after 40
      min and 60 min of exposure to 2 mg/l toluene, respectively, and dropped to 1/2 70
      min and 90 min after exposure cessation: respective values for acetone 10 mg/l
      were 80 and 120 min, and more than 4 hours. A steep rise and a rapid drop was
      characteristic also for the course of blood level and effect during an exposure
      to fluctuating concentrations of toluene: ten minute fivefold jump in the air
      concentration induced a shortlasting seizure inhibition by more than 80%; the
      curves for acetone were flat.

PMID- 8997531
TI  - Exposure to lead and human health in the Czech Republic.
AB  - The aim of presented review is to address the most relevant issues related to the
      health effects caused by the human exposure to lead, as they have been recognized
      in Czech Republic in the period of 1992-1994 within the framework of the National
      Integrated Programme on Environment and Health (NIPEH) approved in 1992 and
      supported by WHO-European Centre for Environment and Health (WHO-ECEH),
      Bilthoven, The Netherlands and by the Government of the Netherlands. Basic
      sources of environment exposure to lead are identified and the fate of lead in
      the individual compartments of the environment is discussed. Relevant methods
      used for the exposure evaluation are summarized and the highest-risk group of
      population is defined. Attention is being paid to the effects of the long-term
      exposure to low lead levels, while other exposure settings are intentionally
      omitted. Interventional measures developed in the Czech Republic in attempt to
      reduce the environmental exposure are introduced. Instead of presenting specific
      data, current state-of-art and general trends are presented; list of references
      tries to combine the internationally recognized studies with those coming from
      national sources.

PMID- 8997532
TI  - Immunological studies on human larval toxocarosis.
AB  - The aim of the study was to characterize the antiparasite humoral response in
      patients with the syndrome of visceral larval toxocarosis. Specific IgG, specific
      IgE and total IgE immunoglobulins against Toxocara canis excretory/secretory
      antigens (TES) were detected by using ELISA technique. Antibody response was
      studied in complete sera as well as in immunoglobulin fractions (IgG and IgE),
      isolation of which was performed on Protein A Sepharose. It was observed that
      removal of IgG from the serum samples resulted mostly in increasing levels of
      anti-Toxocara IgE antibodies what agrees with the theory of the blocking effect
      of IgG in the immune response. The results demonstrated a little correlation
      between slgG and slgE in the sera of symptomatic patients, examined in ELISA
      reaction.

PMID- 8997534
TI  - Environmental health.
AB  - A short history of the close connections between human health an ambient
      environment (environmental health) in the global and national (Czech Republic)
      sense is presented. Concrete tasks and prospects for the near future are
      mentioned, including the human ecology education programme.

PMID- 8997533
TI  - Model of multiple exposure to contaminants in monitoring the environmental impact
      on population health.
AB  - The model study is focused on possibilities of comprehensive evaluation of the
      multiple exposure of humans to selected inorganic contaminants (arsenic, cadmium,
      lead, zinc) monitored within the subsystems of the monitoring the environmental
      impact on population health (inhalation and ingestion exposure from air, drinking
      water and foodstuffs and biological monitoring). The mean daily intake of
      contaminants of average adults is assessed using the monitoring and literature
      data. The exposure balance showed that the total intake of individual
      contaminants studied did not exceed the limit values given by the exposure
      standards (acceptable daily intake). The highest value of exposure reaching 28%
      of the limit was reported for cadmium. The prevailing pathway of exposure is
      ingestion of foodstuffs: more than 95% in all contaminants under study.
      Information on the intake of contaminants is used as input in a linear
      multicompartmental model describing their kinetics and retention in the human
      organism. The results of the model computation are compared with the laboratory
      data obtained in the biological monitoring of adult urine. The model and
      monitoring sets of results were found to conform well for cadmium and zinc. For
      arsenic and lead the model values are roughly one order of magnitude lower than
      the monitored ones which should be considered as acceptable for the model studies
      of this type. The model study of contaminant monitoring data processing and
      evaluation suggests further applications of health risk assessment representing
      one of the basic outputs of monitoring the environmental impact on population
      health.

PMID- 8997535
TI  - Lung function in children of upper Silesian industrial zone, Poland: results of
      the cross-sectional study in two towns of different ambient air pollution levels.
AB  - In two groups of children aged 7-9 years residing in two towns in the most
      industrial region of Poland, Chorzow (C - "higher air pollution") and Mikolow (M 
      "lower air pollution"), lung function testing was performed in a cross-sectional
      manner in order to examine if the spirometric indices in children depended on the
      ambient air pollution level as assessed by area measurements. The between-town
      difference in ambient air quality was statistically significant with respect to
      particulate and gaseous pollutants (SO2 and NO2). In Chorzow 855 and in Mikolow
      356 children were studied. Both groups (C and M) were similar in terms of sex,
      age, height and weight. In boys, the group mean values of lung function indices
      (in% of predicted values) were for FVC: c-98.1, M-98.0; FEV1: C-109.5, M-107.8;
      PEF; C-84.3, M-80.0 (p < 0.05); MEF50: C-105.5, M-100.4 (p < 0.05); MEF25: C
      100.5, M-93.7 (p < 0.05). In girls, the respective values were for FVC: C-100.4,
      M-100.3; FEV1: C-107.6 M-107.1; PEF: C-78.4, M-77.6; MEF50: C-103.5, M-104.2;
      MEF25: C-97.6 M-99.9. Stratification for the presence of respiratory symptoms or
      exposure to environmental tobacco smoke did not change the between-town
      differences in boys' lung function. The findings were confirmed by the results of
      multivariate analyses. The study did not provide evidence that children living in
      Chorzow had poorer lung function compared with children living in Mikolow. The
      results highlight problems regarding a cross-sectional approach to the
      investigation into the effect of ambient air pollution of lung function, such as
      the study design, the validity of exposure assessment by means of stationary
      monitoring, the subjects' age and sensitivity of the evaluation of lung function.

PMID- 8997536
TI  - "Know and improve your health": symbiosis of preventive project and preventive
      medicine education at the medical faculty in Brno.
AB  - At the medical faculty in Brno we succeeded in combining the public health
      improvement project with the practical education of preventive medicine of
      medical students. The project "Know and improve your health" should enable
      individual estimation of the risk factors in people involved and, most of all,
      effectively decrease the risks by individual modification of their lifestyle.
      Until now, 1.588 participants were examined in the framework of the project and
      147 medical students were actively involved during their preventive care
      rotations. Among the identified risk factors, the most prevalent were low
      physical activity (79% females and 75% males), imperfect nutrition (approx. 45%
      females and 65% males), increased level of blood cholesterol (33% females and 47%
      males), overweight and obesity (30 % females and 45% males), excessive alcohol
      intake (3% females and 30% males), increased blood pressure (19% females and 31%
      males) and smoking (22% females and 27% males). The efficiency of the
      intervention is determined by sending brief anonymous questionnaire to the
      participants after several months following the examination. We received 54% of
      the questionnaires back. 87% of respondents state change in their knowledge,
      opinions and attitudes as an effect of the project, 86% state their effort to
      change their lifestyle and 71% successfully realized change in their lifestyle.
      Students taking part in the project are influenced in the sense of "Broader
      application of preventive methods in their future medical practice" (79%
      probably, 21% definitely). Positive effect is perceived as beneficial above
      average by 62% of students for themselves and 59% for examined persons. 96% of
      students and 100% of involved people think the project should go on in future.
      Participation in the real preventive program seems to be very effective form in
      the study of preventive medicine.

PMID- 8997537
TI  - Pesticides and the immune system: the public health risks. Executive summary.

PMID- 8997538
TI  - Environmental aspects of the reuse of former military lands. NATO CCMS Pilot
      Study.

PMID- 8997540
TI  - Predicting the presence of plasma heparin using neural networks to analyze
      coagulation screening assay optical profiles.
AB  - A method for predicting the presence of heparin from coagulation screening assays
      is described and data are presented. This method incorporates the use of a
      multilayer perceptron trained through an error back-propagation algorithm in
      analyzing clotting optical data profiles. This method may lead to the
      identification of abnormalities from screening assays that might otherwise go
      undetected, or require additional testing to isolate.

PMID- 8997539
TI  - Feature discovery and classification of Doppler umbilical artery blood flow
      velocity waveforms.
AB  - Doppler umbilical artery blood flow velocity waveform measurements are used in
      perinatal surveillance for the evaluation of fetal condition. There is an ongoing
      debate on the predictive value of Doppler measurements concerning the critical
      effect of the selection of parameters for the interpretation of Doppler
      waveforms. In this paper, we describe how neural network methods can be used both
      to discover relevant classification features and subsequently to classify Doppler
      umbilical artery blood flow velocity waveforms. Results obtained from 199 normal
      and high risk patients' umbilical artery waveforms highlighted a classification
      concordance varying from 90 to 98% accuracy.

PMID- 8997541
TI  - An expert system for diagnosis and therapy in lung transplantation.
AB  - An expert system for diagnosis and therapy after lung transplantation has been
      developed and evaluated by domain experts. The system captures a total of 21
      diagnoses encompassing rejection, pulmonary infection, and some diseases of
      gastrointestinal origin. The disease hypotheses are scored and ranked by their
      ability to explain the patient findings. A hypothesis is accepted as a candidate
      disease if it is ranked high on the list and is able to account for the cardinal
      findings of the disease. The therapy knowledge is captured in the form of rules.
      The results demonstrate the feasibility of an expert system for diagnosis and
      therapy after lung transplantation.

PMID- 8997542
TI  - A VISUAL BASIC program to pre-process MRI data for finite element modeling.
AB  - Investigators use non-invasive imaging to collect geometric data for finite
      element models. A preprocessor is described to facilitate model generation of
      anatomical regions from serial Magnetic Resonance Imaging (MRI) data stored in a
      bitmap format. The MRI Data Transfer System is a stand-alone Windows-based
      program developed in VISUAL BASIC 3.0 which generates a NASTRAN input file. The
      program can be modified to generate input files for other solvers. The software
      will executive on any IBM-compatible computer which runs Windows Version 3.1 or
      higher. To demonstrate the software, model generation of a portion of a tibia is
      described.

PMID- 8997543
TI  - SCATPLOT: a computer program for determination of binding parameters of non
      linear non-cooperative ligand-substrate interactions.
AB  - The importance of computer-assisted analysis of a non-linear binding phenomenon
      through Scatchard equation has been widely acknowledged. While several user
      friendly softwares [LIGAND, SCTFIT, ALLFIT] are available for determining the
      binding parameters of nonlinear Scatchard phenomenon, there is no easily
      available software covering the class of phenomena described by the McGhee and
      von Hippel formalism [J. Mol. Biol. 86, 469-489 (1974)]. We report here user
      friendly software, SCATPLOT, developed in Turbo BASIC, for the numerical
      estimation of binding parameters of a non-cooperative ligand-substrate
      interaction doing best fit to the experimental data on the basis of McGhee and
      von Hippel equation for a nonlinear Scatchard plot. A new parameter has also been
      incorporated to guide the process of least square analysis and subsequent
      determination of binding parameters.

PMID- 8997545
TI  - A sequential procedure to test the progressive decrease of rare adverse events.
AB  - A program to construct the Rapid Sequential Test (R-ST), a sequential procedure
      to test the decrease of the rate of rare adverse events, is described. This
      sequential procedure is constructed with the Sequential Probability Ratio method.
      It relies on a model for the progressive decrease in the rate of adverse events
      from a given initial rate to a target rate, during a transition period. The
      program allows one to calculate the bounds of rejection of the R-ST, and to study
      its power under various types of decrease. It is shown that the R-ST gives a
      conclusion faster than standard sequential procedures for the same type I and II
      error, saving at least one quarter of the trials completed during the transition
      period. The use of the software to construct R-STs is discussed with respect to
      the specification of the model.

PMID- 8997544
TI  - Comparing non-hierarchical models: application to non-linear mixed effects
      modeling.
AB  - There is no method available to compare the fit of two non-hierarchical non
      linear mixed effects models, although the common practice is to select the model
      with the lower objective function. Bootstrapping the log-likelihood differences
      (LLDs) of non-hierarchical models and constructing a bootstrap confidence
      interval on the LLDs is proposed for comparing the goodness-of-fit of such
      models. This is illustrated with different parameterizations of clearance models
      for an anti-infective agent in a longitudinal pharmacokinetic study which are
      compared. Additive and exponential models of creatinine clearance as a predictor
      of clearance are used as examples.

PMID- 8997546
TI  - Trk neurotrophin receptors in cholinergic neurons of patients with Alzheimer's
      disease.
AB  - Besides cortical pathology, Alzheimer's disease (AD) is characterized by a loss
      of cholinergic neurons in the basal forebrain but not in the caudate nucleus,
      putamen or mesencephalon. Since cholinergic neurons which degenerate in AD are
      sensitive to nerve growth factor (NGF), a link between NGF sensitivity and the
      vulnerability of cholinergic neurons has been suspected. Levels of NGF are not
      altered in patients with AD, however. Thus, cholinergic nerve cell death in AD
      could not result from a deficiency in NGF receptors. Using sequential
      immunohistochemistry with antibodies that recognize preferentially TrkA, the
      specific receptor for NGF, and with antibodies directed against choline
      acetyltransferase we analyzed the expression of neurotrophin receptors in
      cholinergic neurons from control and AD brains. TrkA was expressed on cholinergic
      neurons of the striatum and nucleus basalis of Meynert but not on those of the
      mesencephalon. In AD patients, the number of neurons expressing TrkA was markedly
      decreased in the nucleus basalis of Meynert, very likely as a consequence of
      cholinergic neuronal loss. No loss of TrkA-positive neurons was observed in the
      striatum. Taken in conjunction with our previously published report of loss of
      high-affinity NGF binding in the striatum of AD patients, our results suggest a
      reduced expression of TrkA, the specific receptor for NGF, on striatal
      cholinergic neurons in AD. The loss of neurotrophin receptors may contribute to
      the alteration of cholinergic neurons occurring in AD.

PMID- 8997547
TI  - A multicenter randomized double-blind study on the efficacy and safety of
      nicergoline in patients with multi-infarct dementia.
AB  - A 6-month double-blind, randomized, placebo-controlled clinical trial preceded by
      a 3-week single-blind, washout/run-in placebo phase was performed in male and
      female patients, 55-85 years of age with a clinical diagnosis of mild to moderate
      multi-infarct dementia according to DSM-III to evaluate the therapeutic efficacy
      and safety of nicergoline 30 mg b.i.d. Primary endpoints for efficacy were the
      changes in the Sandoz Clinical Assessment Geriatric Scale (SCAG) and Mini-Mental
      State Examination (MMSE) scores at the end of the treatment with respect to
      baseline. Secondary endpoints were Clinical Global Impression, 3 subtests of the
      Weschsler Adult Intelligence Scale and Blessed A scale for activities of daily
      living, and all endpoints in 2-month intervals. A total of 252 patients were
      screened, 136 patients entered the double-blind phase and were evaluated as
      intent-to-treat (ITT) patients. Fifteen patients were excluded from the efficacy
      analyses of valid cases (VC) due to protocol violations or because they dropped
      out of the study prematurely. Confirmatory efficacy analysis after 6 months of
      treatment revealed superiority of nicergoline treatment with p < 0.01 for both
      SCAG and MMSE scores (ITT and VC). Subsequent descriptive efficacy analysis
      resulted in significant differences in favor of nicergoline, in the majority of
      cases as early as 2 months after start of treatment. Nicergoline was well
      tolerated and a similar number of adverse events were observed in both the
      placebo and the nicergoline group.

PMID- 8997548
TI  - Age vs. aging in the pathogenesis of senile dementia of the Alzheimer type:
      electrophysiological evidence.
AB  - Is senile dementia of the Alzheimer type (SDAT) the end result of aging of the
      brain (serial or aging-related model) or the result of some other mechanism that
      runs in parallel to normal aging (parallel or age-related model)? This question
      can be answered by comparing variables that measure biological aging (aging
      dependent variables, ADVs) of normal individuals and of SDAT patients. If the
      serial model applies, the values of the ADVs of SDAT patients should be at the
      upper end of the normal ADV curves. In control individuals the power of the alpha
      band in the 2-Hz flash-stimulated EEG at the posterior head regions increased
      with age, while the power of the delta band in the resting EEG at the anterior
      head regions decreased. In SDAT patients the ADVs were significantly different
      from normal and opposite to the trend of normal aging, supporting the parallel
      model and suggesting that the pathogenesis of SDAT is different from normal
      aging.

PMID- 8997550
TI  - Neurochemical differences in the CSF between Binswanger's and Alzheimer's
      disease.
AB  - In 21 patients suffering from Binswanger's disease (BD) and in 53 patients
      suffering from Alzheimer's disease, we measured cerebrospinal fluid (CSF)
      concentrations of somatostatin-like immunoreactivity (SLI), high molecular weight
      form somatostatin (HMV-SST), somatostatin-25/28 (SST-25/28), somatostatin-14 (SST
      14), Des-ala-somatostatin (Des-ala-SST), homovanillic acid (HVA) and 5
      hydroxyindoleacetic acid (5-HIAA). The patients were classified into three stages
      of intellectual deterioration according to the global deterioration scale (GDS).
      Levels of SLI were significantly decreased in BD in general and in SDAT patients
      with severe dementia (GDS 7), compared to a control group (BD overall 19.7 +/-
      11.6 fmol/ml, SDAT 18.6 +/- 7.9 vs. 30.5 +/- 8.6 fmol/ml in controls, p < 0.01
      for both). In SDAT patients, SLI levels correlated with dementia scores (r = 
      0.65, p < 0.05), but not in BD. HVA levels were decreased significantly in SDAT
      and BD patients with severe dementia (SDAT 273.5 +/- 138.7, BD 224.3 +/- 69.9 vs.
      364.9 +/- 103.8 nmol/ml, p < 0.01 in controls, p < 0.05 for both). In BD patients
      with light dementia (GDS 2-4), HVA levels were significantly elevated (p < 0.05).
      In BD, HVA levels correlated with dementia (r = -0.59, p < 0.01). 5-HIAA was
      significantly elevated in BD patients with light dementia (p < 0.05). Qualitative
      and quantitative changes in the molecular forms of SLI are compatible with a
      dysregulated posttranslational processing SDAT and BD. We also observed
      significant correlations between SLI, 5-HIAA and HVA in BD indicating a
      neurochemical heterogeneous and generalized process affecting several transmitter
      systems and functions. In summary, our study shows that despite their quite
      different neuropathology, SDAT and BD do not differ fundamentally in their
      neurochemical profile.

PMID- 8997549
TI  - Intracerebroventricular administration of GM1 ganglioside to presenile Alzheimer
      patients.
AB  - We have conducted a preliminary study of the optimum conditions for a therapeutic
      effect of ganglioside GM1 in Alzheimer's disease. Five patients with the early
      onset form of Alzheimer's disease (AD type I) received the ganglioside by
      intracerebroventricular administration for 12 months. Bilateral stereotactic
      punction of the frontal horns of the ventricular system was performed, and shunt
      catheters were implanted and connected to a programmable pump. The optimum GM1
      dose varied between 20 and 30 mg/24 h. Neurological neuropsychological,
      psychiatric and neurochemical examinations were performed 7 days before surgery
      and on days 30, 90, 180 and 360. No patient found the surgery difficult and no
      patient or relative regretted that they participated in the study. The patients
      became more active and safer in relation to others and to performance of various
      activities from day 90. The cerebrospinal fluid level of the monoamine
      metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide
      somatostatin increased.

PMID- 8997551
TI  - In vitro effect of Ginkgo biloba extract (EGb 761) on the activity of presynaptic
      cholinergic nerve terminals in rat hippocampus.
AB  - The effects of Ginkgo biloba extract (EGb) applied in vitro to hippocampal
      synaptosomes from young Wistar rats on the specific binding of [3H]hemicholinium
      3 ([3H]HCh-3), high-affinity choline uptake (HACU) and activity of Na+,K(+)
      ATPase were examined. EGb at a concentration of 100 micrograms/ml markedly
      elevated the specific binding of [3H]HCh-3 (to 306%) and moderately elevated HACU
      values (to 115%). Scatchard analysis revealed an increase in the Bmax for [3H]HCh
      3 binding. Lineweaver-Burk analysis an increase in the Vmax for choline uptake.
      No marked changes in the activity of the sodium pump were discovered. EGb was not
      able to influence the specific 'second messenger' effect of arachidonic acid.

PMID- 8997552
TI  - Tone duration discrimination in demented, memory-impaired, and healthy elderly.
AB  - In order to assess the diagnostic validity of a new test of tone duration
      discrimination (TDD), we tested elderly subjects, 32 Alzheimer-type (AD) and 11
      vascular-type dementia (VAD) patients, 11 memory-impaired (MI), and 21 healthy
      controls with a TDD test as well as with 18 standard neuropsychological (NP)
      tests. The TDD test efficiently discriminated demented patients from MI, and MI
      from controls. As an index of cognitive impairment, the TDD test was sensitive
      also in comparison to NP tests. This suggests that processing of auditory
      duration information is impaired in dementia as well as in MI. Patients suffering
      from AD and VAD differed in that the VAD but not the AD patients improved their
      TDD performance when the interstimulus interval was lengthened. This shows that
      the processing of auditory temporary information involves functions sensitive to
      dementia diseases as well as to MI. The TDD test could add discriminatory power
      in diagnosis and differential diagnosis of dementia.

PMID- 8997553
TI  - Non-Alzheimer dementia with status spongiosus and neuronal cell loss showing
      unusual perineuronal structures and point mutation at 129 codon of prion protein.
AB  - The subject presented with intellectual decline followed by progressive muscle
      weakness of the bilateral upper limbs when he was 60 years old. He had a point
      mutation (methionin-valine) at 129 prion protein codon. He died at the age of 63
      and necropsy revealed bilateral frontal lobe atrophy. The frontal cortex showed
      neuronal cell loss in layers II and III with spongiform change. Reusche silver
      impregnation technique for beta-peptide combined with ubiquitin immunostaining
      revealed perineuronal structures encircling degenerated neurons and ubiquitin
      immunoreactive (IR) dot-like deposits. They were distributed particularly in the
      temporal neocortex and entorhinal cortex. They differed from either classic
      senile or diffuse plaque by the absence of amyloid core in the center and of
      amyloid fibrils. Ubiquitin-IR materials were also found as neuronal inclusions in
      the hippocampal granular cells. Nigral degeneration and neuronal loss in the
      hypoglossal nerve nucleus and in the anterior horn of the spinal cord were also
      found and spinal cord motoneurons had Bunina body inclusions. The clinical
      features and pathological findings were consistent with non-Alzheimer dementia
      with status spongiosus and neuronal cell loss. The unusual perineuronal
      structures found in our case might be a specific cellular pathology of dementia
      of the frontal lobe type.

PMID- 8997554
TI  - Screening for mutation of the presenilin 2 gene in Alzheimer's disease.

PMID- 8997555
TI  - Efficacy and safety of azithromycin versus phenoxymethylpenicillin in the
      treatment of acute maxillary sinusitis.
AB  - In the treatment of acute maxillary sinusitis, azithromycin offers an advantage
      over phenoxymethylpenicillin in that a complete course of treatment requires drug
      administration once daily for only three days. In this double-blind, parallel
      group, multicenter study, 438 patients with radiographically verified maxillary
      sinusitis were randomly assigned to receive either 500 mg azithromycin once daily
      for three days (221 patients) or 1.3 g phenoxymethylpenicillin three times daily
      for ten days (217 patients). Nasal secretion, maxillary tenderness and pain,
      nasal obstruction, general malaise, and hyposmia, were assessed at the start of
      the study and on days 4, 11, and 25 of treatment. After 11 days 58% of the
      patients in the azithromycin group were cured versus 51% in the penicillin group;
      after 25 days the cure rate was 79% versus 76%, respectively. When both cure and
      improvement were considered, the corresponding figures after 11 days were 97%
      (azithromycin) and 95% (penicillin); after 25 days they were 92% and 88%,
      respectively. Adverse events, predominantly gastrointestinal, occurred in 73
      (33%) of the azithromycin-treated patients and in 87 (40.1%) of those treated
      with penicillin. No difference in efficacy was found between the two drugs in the
      treatment of acute maxillary sinusitis, and the adverse effects were comparable.
      The short duration of treatment with azithromycin offers a significant advantage
      over treatment with phenoxymethylpenicillin.

PMID- 8997557
TI  - Prevalence of primary Helicobacter pylori resistance to metronidazole and
      clarithromycin in The Netherlands.
AB  - The minimum inhibitory concentrations of metronidazole and clarithromycin were
      determined for 780 Helicobacter pylori strains collected in 1994 and 1995 from
      three different regions in The Netherlands. The overall prevalence of primary
      metronidazole resistance was 17%, with resistance found more frequently in women
      (24%) than in men (13%). There was no significant difference between the levels
      of resistance in the three regions. Primary clarithromycin resistance was rare
      (1%) and relatively infrequent as compared to that found in other countries. Four
      of the six strains resistant to clarithromycin were also resistant to
      metronidazole.

PMID- 8997556
TI  - Variable antifungal susceptibility of wild-type Candida albicans phenotypes from
      neutropenic hosts.
AB  - The aim of the present study was to investigate the relationship between
      phenotypes of Candida albicans strains isolated from clinical specimens and
      susceptibility of the strains to two antifungal agents, itraconazole and
      fluconazole. Oropharyngeal, gastrointestinal tract, and urogenital tract
      specimens were collected from 131 neutropenic patients with Candida infection who
      had received no previous prophylactic treatment. The most frequent species
      isolated was Candida albicans, followed by Candida glabrata, Candida tropicalis,
      Candida krusei, and Candida parapsilosis. Each of the 44 Candida albicans strains
      recovered was found to express one of four phenotypes: smooth, irregular, fuzzy
      or stipple. Mean minimum inhibitory concentrations (MICs) of itraconazole and
      fluconazole as determined by the microdilution method and the E-test were
      consistently higher for Candida albicans strains expressing the stipple
      phenotype. The mean MICs for the four phenotypes of the Candida albicans strains
      ranged between 0.35 microgram/ml and 2.41 micrograms/ml for itraconazole and 2.78
      micrograms/ml for fluconazole. Antifungal susceptibility of the stipple phenotype
      requires careful appraisal, especially in patients clinically unresponsive to
      azole chemotherapy or in cases of life-threatening, deep-seated Candida
      infections.

PMID- 8997558
TI  - First European case of gastroenteritis and bacteremia due to Vibrio hollisae.
AB  - Vibrio hollisae is a pathogenic Vibrio species known to cause gastroenteritis in
      humans after the consumption of shellfish. All cases of infection reported
      previously were restricted to the Atlantic and Pacific coasts of the United
      States. A case of gastroenteritis and bacteremia in a previously healthy 76-year
      old man who ate cockles from the Quiberon Bay in Brittany, France, is described.
      This is the first report of Vibrio hollisae infection in Europe.

PMID- 8997559
TI  - Role of granulocyte colony-stimulating factor in the treatment of mucormycosis.
AB  - Several problems in the management of life-threatening mucormycosis remain
      unresolved, necessitating new methods of management. Four patients with
      histopathologically proven rhinocerebral mucormycosis were treated with high
      cumulative doses of granulocyte colony-stimulating factor (G-CSF). All had
      multiple predisposing factors for mucormycosis, particularly leukemia and
      neutropenia. Two patients refractory to fluconazole therapy were treated with
      liposomal amphotericin B. The improvement in clinical manifestations was closely
      related to neutrophil recovery, and all patients were alive at the end of
      therapy. In addition to surgical debridement and antifungal therapy, G-CSF seems
      to have played a role in their survival.

PMID- 8997560
TI  - High predictive value of Toxoplasma gondii IgG antibody levels in HIV-infected
      patients for diagnosis of cerebral toxoplasmosis.
AB  - The results of serological tests for Toxoplasma gondii IgG in 31 HIV-infected
      patients with toxoplasmic encephalitis (TE) and 49 HIV-infected patients
      seropositive for Toxoplasma gondii but without TE were compared. All patient had
      a CD4+ lymphocyte count < 150/microliters. Of the TE patients, 22 (71%) were
      designated as having relatively high IgG levels on the basis of the following
      Toxoplasma IgG titre combination: Sabin-Feldman test > or = 1:256, indirect
      hemagglutination test > or =1:1024, direct agglutination test > or = 1:14,580.
      Only 3 patients without TE had relatively high IgG titres. Relatively high IgG
      titres indicated TE with a positive predictive value of 88% in HIV-infected
      patients with CD4+ cell counts < 150/microliters, and could be observed in most
      patients several months prior to the first clinical and radiological signs of TE.

PMID- 8997561
TI  - Antibiotic resistance in Shigella and Salmonella in a region of Lithuania.
AB  - To gather information on the antibiotic susceptibility of Shigella and Salmonella
      in the Baltic countries, 98 Shigella and 100 Salmonella isolates collected
      consecutively in 1994 were examined. All Shigella isolates were resistant to at
      least two of 12 antibacterial agents: 100% were resistant to oxytetracycline, 92%
      to trimethoprim/sulfamethoxazole, 64% to chloramphenicol, and 64% to ampicillin.
      Five different resistance patterns were observed.

PMID- 8997562
TI  - Molecular epidemiology of Burkholderia cepacia, Stenotrophomonas maltophilia, and
      Alcaligenes xylosoxidans in a cystic fibrosis center.
AB  - Burkholderia cepacia, Stenotrophomonas maltophilia, and Alcaligenes xylosoxidans
      have been isolated with increasing frequency from the sputum of patients with
      cystic fibrosis in a pediatric hospital. In 1994-95, 27 of 120 patients were
      persistently colonized, 17 with Burkholderia cepacia, eight with Alcaligenes
      xylosoxidans, and five with Stenotrophomonas maltophilia. Genotyping of 220
      clinical isolates revealed that most of the Burkholderia cepacia strains were
      clonally related, suggesting either cross-infection or a common source of
      exposure. In contrast, neither cross-infection nor a common source of exposure
      appear to have occurred in the cases of Alcaligenes xylosoxidans or
      Stenotrophomonas maltophilia.

PMID- 8997564
TI  - Modified enzyme immunoassay to detect hepatitis C virus antibodies in oral fluid.
AB  - Samples of oral fluid collected from 18 patients seropositive for hepatitis C
      virus (HCV) and 49 seronegative patients were tested for the presence of HCV
      antibodies with two modified serum-screening kits. The following sensitivities
      and specificities were obtained: HCV 3.0 assay, 72% and 98%, respectively, and
      Monolisa anti-HCV assay, 100%, and 100%, respectively. The modified Monolisa
      assay demonstrated a striking concordance between serum and saliva samples. The
      use of oral fluids offers a convenient and noninvasive method applicable to HCV
      epidemiological studies and screening of high-risk groups.

PMID- 8997565
TI  - Relationship between viral genotype and viral load in patients with chronic
      hepatitis C.
AB  - To determine the distribution of hepatitis C virus (HCV) genotypes and to related
      genotype to viral load, genotyping and quantification of viral RNA were carried
      out in 35 patients with chronic hepatitis C. Subtype 1a was most prevalent (43%),
      followed by subtypes 1b (23%) and 3a (14%). Mean viral load (log HCV-RNA
      copies/ml) for subtypes 1b, 1a and 3a was 7.1 +/- 1, 5.6 +/- 1.1 and 4.1 +/- 2.4,
      respectively. The presence of immunoglobulin M was related to the duration of
      hepatitis and genotype 1 to a more severe hepatic injury and higher viral load.
      Differences observed in viral load for a single HCV subtype justify the need to
      quantify HCV-RNA prior to establishing antiviral therapy.

PMID- 8997563
TI  - Activity of trimethoprim/sulfamethoxazole plus polymyxin B against multiresistant
      Stenotrophomonas maltophilia.
AB  - The inhibitory activity of eight antibiotics and the inhibitory and bactericidal
      activities of combinations of trimethoprim/sulfamethoxazole (TMP/SMX) plus three
      fixed concentrations of polymyxin B (0.01 microgram/ml, 0.1 microgram/ml and 0.5
      microgram/ml) against 30 multi-resistant strains of Stenotrophomonas maltophilia
      were tested. Polymyxin B at 0.01 microgram/ml modified the inhibitory activity of
      TMP/SMX against only 40% of strains. At 0.1 microgram/ml and 0.5 microgram/ml,
      polymyxin B enhanced the inhibitory activity of TMP/SMX activity against all
      strains. Polymyxin B enhanced the bactericidal activity of TMP/SMX only at
      concentrations near the minimum inhibitory concentration of polymyxin B alone.

PMID- 8997566
TI  - Detection of hepatitis C virus RNA in serum and peripheral blood mononuclear
      cells in patients with chronic hepatitis C treated with interferon alpha.
AB  - PCR was used to detect hepatitis C virus (HCV) RNA in serum and peripheral blood
      mononuclear cells (PBMCs) for evaluation of a six-month course of interferon
      therapy in 18 patients with histologically confirmed chronic hepatitis C. At
      follow-up six months after the end of therapy positive-stranded (genomic) and
      negative-stranded (anti-genomic, presumptive replicative intermediate) HCV RNA
      could be detected in PBMCs of all ten patients who either did not respond to
      therapy or suffered a relapse; genomic strand RNA was detected in five patients
      who responded but then relapsed. The study confirms that interferon therapy leads
      to inhibition of HCV replication but not eradication of the virus. Persistence of
      the virus at extrahepatic sites may explain its reactivation after cessation of
      interferon therapy.

PMID- 8997568
TI  - Vertebral osteomyelitis and meningitis due to a penicillin-resistant pneumococcal
      strain.

PMID- 8997567
TI  - Spinal cord compression due to concomitant primary lymphoma and Mycobacterium
      avium-intracellulare infection of the paravertebral muscles in an AIDS patient.

PMID- 8997569
TI  - Comparison of four methods for pretreatment of cystic fibrosis sputa.

PMID- 8997571
TI  - Inhibition of complete development of Cryptosporidium parvum in Caco-2 cells.

PMID- 8997570
TI  - Isolation of Mycoplasma hominis on CDC anaerobic blood agar.

PMID- 8997572
TI  - Viral load in relation to clinical outcome in HIV-infected children.

PMID- 8997573
TI  - Hyperopic shift after 4-8 incision radial keratotomy: eight-year follow-up.
AB  - PURPOSE: To evaluate the prevalence, amount and possible factors connected with
      the hyperopic shift after radial keratotomy. BASIC PROCEDURES: We studied 86 eyes
      (51 patients) which underwent 4-8 incision radial keratotomy (delayed technique),
      consecutively performed by the same surgeon between February 1983 and November
      1988. The diamond-bladed knife was set at 95% of the smallest paracentral
      ultrasonic corneal thickness measurement and the clear zone diameter was between
      3.0 and 3.5 mm. Preoperative myopia ranged from -2.00 to -7.25 diopters (D). The
      average follow-up was 97.4 months (range 78 to 122 months). MAIN FINDINGS: After
      eight years of follow-up, the cycloplegic spherical equivalent was satisfactory:
      66.2% of the eyes showed a refractive error within 0.5 D, 17.4% were myopic by
      more than 0.5 D and 16.2% were hyperopic by more than 0.5 D. The mean refractive
      error was 0.02 D (SD +/- 0.75 D). Between six months and eight years after
      surgery a hyperopic shift of more than 0.5 D was found in 40.6% of the eyes. The
      mean hyperopic shift was higher (0.78 D) in the eyes which had keratometry less
      than 36 D six months after surgery. Compared to the eyes with keratometry greater
      than 36 D (mean hyperopic shift 0.38 D), the difference was statistically
      significant (p < 0.02). CONCLUSIONS: These results show that keratometry,
      measured six months postoperatively, plays a fundamental role in the stability of
      postsurgical refraction, as the risk of hyperopic shift is higher in eyes with
      keratometry < 36 D.

PMID- 8997574
TI  - Intraocular lens implantation in myopic eyes.
AB  - PURPOSE: To assess the results of posterior chamber lens implantation in myopic
      eyes with cataract. METHODS: Retrospective study of postoperative results ranging
      from 4 to 89 months (mean 35 months) in 54 myopic patients (62 eyes with axial
      length of 26 mm or more) who had undergone PC IOL implantation in the Department
      of Ophthalmology, Medical Academy of Bydgoszcz, Poland. OUTCOME MEASURE: Best
      corrected distance and near visual acuity, operative complications, early and
      late postoperative complications. RESULTS: in 95% of patients with eye length 26
      28 mm visual acuity of 0.5 or more was achieved. The mean postoperative spherical
      equivalent was -0.8 D. Posterior capsule opacification which required Nd: YAG
      capsulotomy developed in 19% of eyes, on average after one year of follow-up. No
      complications such as retinal detachment, glaucoma or corneal dystrophy were
      observed. CONCLUSIONS: PC IOL implantation in myopic eyes with cataract appears
      to be an efficacious, satisfactory and safe procedure.

PMID- 8997575
TI  - Comparative evaluation of the short-term bactericidal potential of a steroid
      antibiotic combination versus steroid in the treatment of chronic bacterial
      blepharitis and conjunctivitis.
AB  - The effects of four days' treatment with topical Maxitrol (neomycin sulphate 3500
      IU/mL, polymyxin-B sulphate 6000 IU/mL with dexamethasone 0.1%) were compared
      with those of Maxidex (dexamethasone 0.1% alone) in a double-masked study in 111
      patients with bacterial blepharitis or conjunctivitis, 95 of whom were evaluable
      for efficacy. The majority of patients (N = 80) had chronic blepharitis. Maxitrol
      treatment resulted in a significantly greater reduction (90%) in bacterial counts
      and bacterial eradication (50%) compared with Maxidex (34% and 17% respectively).
      Maxitrol treatment also produced a significantly greater reduction in
      conjunctival discharge than did Maxidex, while the treatments were equally
      effective in alleviating other ocular signs and symptoms. It was concluded that
      use of a fixed dose combination steroid-antibiotic product was more effective for
      bacterial control and therapeutic efficacy in the treatment of chronic
      blepharitis and conjunctivitis patients than treatment with steroid alone.
      However, in the long-term treatment of chronic blepharitis the well-known toxic
      problems of neomycin sulphate have to be taken into account.

PMID- 8997576
TI  - Ciprofloxacin ophthalmic solution in the treatment of conjunctivitis and
      blepharitis: a comparison with fusidic acid.
AB  - The efficacy and safety of ciprofloxacin ophthalmic solution (0.3%) and fusidic
      acid gel (1%) were compared in the treatment of bacterial conjunctivitis and
      blepharitis in a randomized, open, parallel group study. Thirty-nine patients, 21
      treated with ciprofloxacin solution and 18 treated with fusidic acid gel, were
      culture-positive on admission and were evaluable for efficacy. At the end of a 7
      day treatment, the infecting organism was eradicated in 81% of those treated with
      ciprofloxacin and 72% of those treated with fusidic acid gel. There was clinical
      cure or improvement in 95% and 89% respectively. The clinical cure rate appeared
      to be higher with ciprofloxacin than fusidic acid (62% compared with 28%) but
      this was related to the higher proportion of patients with acute conjunctivitis
      in the ciprofloxacin group. Two patients using ciprofloxacin had mild discomfort
      and stinging on instillation and one given fusidic acid had moderate edema and
      discomfort; the latter patient stopped treatment. Topical ciprofloxacin is
      effective and well tolerated and is a useful treatment of bacterial
      conjunctivitis and blepharitis.

PMID- 8997578
TI  - Prevention and management of posterior capsule rupture.
AB  - PURPOSE: To present the means and technique used in our Department for prevention
      and management of posterior capsule rupture during planned extracapsular cataract
      extraction. METHODS: Prospective analysis of 550 extracapsular cataract
      operations from October 1993 to March 1994. Our technique (a slight modification
      of Blumenthal's technique) included a triplanar watertight small scleral
      incision, a relatively large continuous curvilinear capsulorhexis, or can-opener
      capsulotomy, nucleus hydrodissection and hydroexpression, use of an anterior
      chamber maintainer and residual cortex removal through a 10 o'clock side-port
      corneal incision. RESULTS: Best corrected postoperative visual acuity ranged from
      7-10/10 in 93.45% of our cases. Posterior capsule rupture with or without
      vitreous loss occurred in 1.63% and 2.72% of the cases, respectively. These rates
      are much lower than those, observed, when we used the sclerocorneal incision and
      nucleus extraction with external pressure. CONCLUSIONS: The combination of a
      triplanar watertight small scleral incision. A relatively large continuous
      curvilinear capsulorhexis, an anterior chamber maintainer and residual cortex
      aspiration through the 10 o'clock side-port corneal incision greatly reduced the
      posterior capsule rupture rate.

PMID- 8997577
TI  - Calculation of intraocular lens power with the SRK II formula for axial high
      myopia.
AB  - AIM: The SRK II formula has been widely used for intraocular lens (IOL) power
      calculations. The predictability of this formula is evaluated in axial myopic
      patients. METHODS: Planned extracapsular cataract extraction and posterior
      chamber IOL implantation (PECCE + IOL) were performed on 98 eyes of 98 patients
      with axial length > 24.5 mm. Cases had no preoperative complications and
      postoperative visual acuity was at least 0.5 (Snellen). Corneal refractive power
      and axial length were measured preoperatively and emmetropic IOL power
      calculations were made using the SRK II formula. Long-term (mean 4.7 months)
      visual acuities and refractions were noted postoperatively. RESULTS: The absolute
      refractive error was < 1.00 Diopters (D) in 57 eyes (58.2%) and < 2.00 D in 83
      eyes (84.7%). The mean absolute error of the SRK II formula in axial myopia was
      1.16 D +/- 0.78 SD. CONCLUSIONS: The SRK II formula is not very accurate in axial
      myopic patients.

PMID- 8997579
TI  - Sulcus fixated posterior chamber lenses with and without suture in cases lacking
      capsular support.
AB  - In a prospective study ten commercially available anterior chamber lenses with S
      shaped haptics and multipoint support were implanted into the posterior chamber
      in cases of secondary lens implantation after intracapsular cataract operation.
      The lenses were trans-sclerally fixed by two sutures through the ciliary sulcus.
      They showed more immediate stability than ten C-loop posterior chamber lenses of
      a control group and remained firmly fixed without complications during a follow
      up of up to 54 months. To overcome the disadvantages of suture fixation a
      sutureless sulcus self-fixation PCL was developed and implanted into six eyes
      with special indications. After more than one year of follow-up no late adverse
      reaction was noted.

PMID- 8997580
TI  - Comparative study of astigmatism through superior and lateral small incisions.
AB  - PURPOSE: To prospectively compare the clinical results of two cataract surgery
      procedures through a 4.0-mm incision, differing only in the wound location
      (superior or lateral). METHODS: 168 eyes with cataract were randomly assigned to
      either procedure. Except for incision location, surgical methods were identical.
      Uncorrected visual acuity, keratometry and postoperative astigmatism were
      analyzed up to six months for after surgery. RESULTS: Both groups had similar
      uncorrected visual acuity. Eyes in the superior incision group had significantly
      larger "against-the-rule" changes than those in the lateral incision group, and
      differences were significant at all measurement points from one week through six
      months after surgery. Patients with preoperative "with-the rule" astigmatism had
      smaller postoperative astigmatism after a superior incision and those with
      preoperative "against-the rule" astigmatism had less postoperative cylinder after
      a lateral incision. Differences between these groups were significant.
      CONCLUSIONS: Both procedures gave satisfactory clinical results. Postoperative
      astigmatism could depend on the preoperative astigmatism and the wound location.

PMID- 8997581
TI  - Management of delayed massive suprachoroidal hemorrhage: a clinical retrospective
      study.
AB  - Suprachoroidal hemorrhages, both expulsive and delayed non-expulsive, are among
      the most devastating complications of intraocular surgery. We reviewed the charts
      of 13 patients with a delayed non-expulsive suprachoroidal hemorrhage (DNSCH)
      after cataract extraction (3 patients), glaucoma filtering surgery (6 patients),
      penetrating keratoplasty (3 patients), or vitrectomy (1 patient). All had large
      hemorrhagic choroidal detachments with nine eyes presenting kissing choroidal
      detachment, five eyes with associated retinal detachment, and one eye with
      intravitreous hemorrhage. All patients were treated with systemic corticosteroids
      before surgery. Eleven eyes underwent anterior drainage sclerotomy, followed by
      SF6 gas injection in eight eyes, and pars plana vitrectomy with silicon oil
      tamponade in three eyes. Mean follow-up was 22 months. These procedures gave good
      anatomical results in eleven cases and good visual results in nine. The results
      suggest that not all DNSCH need to be drained surgically but that, when surgical
      drainage is indicated, the use of gas to maintain internal tamponade appears to
      be beneficial.

PMID- 8997583
TI  - Clinical use of a new method for visual field damage classification in glaucoma.
AB  - This new method, based on the use of MD and CPSD (or CLV) visual field indices,
      can instantly classify not only the stage of glaucomatous visual field damage,
      but also the type of defect (localized, generalized or mixed). This system was
      used to study glaucomatous visual field defects in 500 automated tests, performed
      with either Humphrey 30-2 or Octopus G1 threshold tests. The most common defects
      found were mixed, and purely local defects were very unusual, especially in
      advanced glaucoma.

PMID- 8997582
TI  - A comparative clinical trial of mitomycin C and cyclosporin A in trabeculectomy.
AB  - This prospective, randomized clinical trial assessed the effects of mitomycin C
      and cyclosporin A used as antimetabolites in trabeculectomy on the post-operative
      IOP and success rate. Eighty-six consecutive patients were randomly allocated to
      three treatment groups. There were 30 patients in the mitomycin C group, 28 in
      the cyclosporin A group and 28 in the control group. The follow-up periods were
      different for the three groups and ranged from 6 to 30 months. The treatment
      groups consisted of primary open-angle glaucoma, closed-angle glaucoma, various
      secondary glaucomas and prior failed trabeculectomy. There were no significant
      differences pre-operatively with respect to IOP and number of medications used (p
      > 0.05). Postoperative IOP was considered to be successfully reduced when it was
      reduced by more than 25% from baseline or when it was lower than 20 mmHg.
      According to these criteria, IOP was under control in 90% of the mitomycin C
      treated eyes, 85.7% of cyclosporin A treated eyes and 71.4% of the control eyes.
      Postoperatively there was a significant decrease in IOP (p < 0.01) and in the
      number of medications need to control IOP (p < 0.01) in the mitomycin C and
      cyclosporin A groups. Post-operative IOP and number of medications in the
      mitomycin C and cyclosporin A group were similar. Complications encountered in
      the three groups were similar. There were no serious complications like hypotonus
      maculopathy. Our study highlights the utility of mitomycin C as an adjunct in
      glaucoma filtering surgery and indicated that cyclosporin A may also be used as
      an antimetabolite.

PMID- 8997584
TI  - Stato-kinetic dissociation in subjects with normal and abnormal visual fields.
AB  - PURPOSE: The aim of the study was to assess the presence and the importance of
      stato-kinetic dissociation (SKD) in subjects with normal and pathological visual
      fields (VF). METHODS: A "customized" perimetric test designed for the assessment
      of SKD was carried out in seven homogeneous samples of subjects (normal,
      glaucomatous, ocular hypertensive, retinopathic, cataract, anterior visual
      pathways neuropathic and posterior visual pathways neuropathic). The results were
      statistically compared (Anova). RESULTS AND CONCLUSIONS: SKD is a physiological
      phenomenon, more evident in the central, paracentral and superior VF, influenced
      by age and partially by sex. SKD increases in the VF periphery when a posterior
      visual pathway disorder or retinopathy is present, and decreases in the centro
      paracentral VF of glaucomatous and ocular hypertensive eyes. This SKD behaviour
      should be useful for early diagnosis of glaucoma.

PMID- 8997585
TI  - Treatment with bifemelane for optic nerve damage following high intraocular
      pressure in rat eyes.
AB  - This study found that pretreatment with 4-(o-benzylphenoxy)-N- methylbuty-lamine
      hydrochloride (bifemelane hydrochloride, Celeport) reduced ischemia-reperfusion
      injury in rat eyes. Bifemelane (25 mg/kg) was injected intraperitoneally 30
      minutes before an ischemic insult, then acute ischemia of the retina and optic
      disc was induced by increasing intraocular pressure to 110 mmHg for 45 minutes.
      After one week, the axonal count of the optic nerve was investigated using
      electron microscopy. The control group consisted of vehicle-treated eyes which
      received normal saline. The axon count was 93.4 +/- 7.9 for the bifemelane
      treated group, and 79.2 +/- 6.4 for the controls. The axon count in the treated
      group was significantly higher. These results suggest that bifemelane, which
      prevents cerebral nerve cell damage from ischemia, can reduce ischemic retinal
      nerve cell injury.

PMID- 8997586
TI  - Congenital glaucoma associated with an arginase deficit: a case report.
AB  - PURPOSE: Argininemia is a rare congenital disease caused by deficiency. We
      present here a case in which argininemia and buphthalmos are associated. CASE
      REPORT: This female patient, who died at eighteen, had intraocular pressure
      correlated with her blood levels or arginine. Hyperammoniemia causes a change in
      pH that could explain an increase in aqueous humor (from the ciliary body).
      Ammonium ions could also damage the matrix of the trabecular meshwork.
      CONCLUSIONS: The association of argininemia and buphthalmos have never been
      described. This might be because of the different expressions of the disease, or
      because nobody has ever looked for ocular hypertension in these patients unless
      they had subjective symptoms.

PMID- 8997588
TI  - A retrospective study of ocular side effects in children undergoing bone marrow
      transplantation.
AB  - Bone marrow transplantation (BMT) is recognized as a successful treatment for
      malignant and non-malignant hematological diseases. Thanks to transplantation,
      the number of long-term survivors has risen and with the improved prognosis a
      problem of ocular side effects has arisen. We carried out a retrospective study
      to determine the incidence and etiopathogenesis of ocular complications in a
      series of young patients undergoing BMT. One hundred children (62 males and 38
      females) with a mean age of 7.12 (+/- 3.3) years at the time of BMT (autologous
      in 66 cases, allogenic in 34) were followed for a mean of 4.2 years (range 2-9).
      The conditioning regimens preceding BMT induced cytoreductive chemotherapy alone
      (47 cases) or associated with total body irradiation (TBI) (53 cases) in three or
      six fractions for a total dose of 10-12 Gy. We examined every child before BMT
      and subsequently every six months. We did not include patients with ocular
      complications due to the primary disease. Thirty-three children showed several
      complications after BMT: 17 had subcapsular posterior cataract in both eyes and
      eight had tear hyposecretion; one had dramatic fungal panuveitis, four had
      hemorrhagic complications and five optic disk edema. TBI was significantly
      associated with the development of subcapsular posterior cataract.

PMID- 8997587
TI  - Ocular abnormalities in transgenic mice harboring mutations in the type II
      collagen gene.
AB  - PURPOSE: To characterize the morphological changes in the eyes of transgenic mice
      harboring different mutations in type II collagen gene to elucidate the function
      of this collagen in the eye, and to find out whether these animals could function
      as models for the human arthro-ophthalmopathies of the Kniest, Stickler and
      Wagner types. METHODS: Three genetically engineered mouse lines representing two
      types of mutations in the triple-helical domain of type II collagen and their
      nontransgenic littermates used as controls were analyzed on day 18.5 embryonic
      development. After genotyping by polymerase chain reaction (PCR) and Southern
      hybridization the embryos were prepared for routine histology. Polarization
      microscopy was done on hyaluronidase-treated sections. RESULTS: Histological
      analysis revealed several genotype-dependent abnormalities in the eyes of the
      transgenic mice. Most striking changes were observed in the vitreous
      architecture; in one line of mice the vitreous was tightly packed in the
      posterior region of the vitreous space with thick fibrils, empty cavities and
      dense membrane-like material. The other mutation resulted in reduced filament
      density of the vitreous. In the most severely affected phenotype the internal
      limiting membrane was detached from the retinal layers and was markedly
      thickened, and the posterior lens capsule was thickened. The anterior chamber was
      shallow or absent in all transgenic lines but was well formed in the normal
      animals. Changes were also observed in the lens, corneal and scleral structures.
      CONCLUSIONS: The ocular changes observed in transgenic mice harboring mutations
      in type II collagen gene show similarities to the human ocular findings in Kniest
      dysplasia, and in Stickler and Wagner syndromes. We therefore propose that these
      animals could serve as models for systematic analysis of vitreoretinal
      degeneration and other abnormalities, as seen in these syndromes.

PMID- 8997589
TI  - Epidemiological studies on occupational eye pathology.
AB  - We examined 522 persons exposed to different types of non-ionizing radiation (UV,
      IR lasers) in the working environment. The control group consisted of 250
      persons. The clinico-statistical analysis of occupational eye pathology depending
      on etiological factors, exposure time and age is presented. Specific cataracts
      were found in 38.37% of electric welders and in 11.4% of metal workers. The
      number of cataracts increased with exposure time and in elderly workers. We also
      observed six macular incidents when working with lasers. The results show the
      potential hazardous factors of the working environment and the corresponding eye
      impairments.

PMID- 8997590
TI  - Esotropia and pseudoexotropia in acute ROP sequelae: clinical features and
      suggestions for treatment.
AB  - We report five cases with a mixture of esotropia and pseudoexotropia due to
      macular ectopia related cicatricial retinopathy of prematurity (ROP). On
      inspection, the patients, aged from 9 to 28 years, presented a divergence of the
      eyes and a nasally decentralised corneal light reflex. The cover test showed
      esodeviation. All the cases presented some clinical features common to congenital
      strabismus. Fundus examination showed temporal traction of vascular and retinal
      tissues and macular ectopia, referrable to cicatricial sequelae of spontaneously
      regressed severe ROP. Treatment is limited to follow-up, with attention being
      paid to the control of retinal damage rather than to resolving the esthetic
      defects. Despite cryotherapy, these conditions are increasing with the increase
      in severe ROP and are now relatively frequent. We suggest that they be carefully
      identified in order to avoid incorrect orthoptic or surgical treatment.

PMID- 8997591
TI  - Silicone oil for complicated retinal detachment in the pediatric population.
AB  - We presented our results with silicone oil in vitreoretinal surgery in pediatric
      patients. The retinas reattached in 58% but corneal opacification occurred in 75%
      and glaucoma in 25%. Our results indicate that silicone oil should be considered
      in otherwise hopeless cases of retinal detachment surgery in children.

PMID- 8997592
TI  - Automatic speech recognition in vitreo-retinal surgery. A project for a
      prototypal computer-based voice-controlled vitrectomy machine.
AB  - In the past half decade automatic speech recognition techniques, software and
      hardware technology have matured enough to support sophisticated medical
      applications. The project described aimed at introducing a computer-based, voice
      controlled prototype system in a simulated vitreo-retinal surgery scenario. The
      aim was to provide the surgeon with a tool that could significantly improve the
      quality and ease of work and shorten the duration of intervention. The speech
      recognition system allows voice entry of simple commands to simulate surgical
      instrument control, including the infusion pump, vitreous cutter and diathermy.
      The project relies on a Markov-based, speaker-dependent, commercial isolated-word
      recognizer, and consists of a specific recognition vocabulary and application
      software, created and developed by the authors. Results have been encouraging.
      The system performed well under the test conditions, proving robust, simple to
      use and accurate (over 97% average word recognition rate). On the basis of their
      experience, the authors believe that automatic speech recognition technology,
      though suffering from some limitations such as the need for training, speaker
      dependence and a relatively small vocabulary, and requiring extensive testing
      under operating conditions, merits further development and opens new perspectives
      for a possible new generation of surgical instruments.

PMID- 8997593
TI  - Vitrectomy for ocular trauma: a question of timing?
AB  - PURPOSE: A long-standing controversy exists regarding the proper timing for
      vitrectomy in a traumatized eye. The present study was conducted to assess the
      influence of timing on the final visual acuity. MATERIALS AND METHODS: A
      retrospective review was made of 45 consecutive patients who underwent a pars
      plana vitrectomy procedure for repair of ocular trauma. The patients were divided
      into two groups according to the timing of the surgery post-trauma: those
      operated before or after 14 days. Type of trauma and pre- and postoperative
      visual acuities were compared. RESULTS: A contusion type of trauma was more
      frequent in the late surgery group. Sharp, penetrating injuries were more common
      in the early vitrectomy group. No significant difference was found though visual
      acuity was worse in the patients with a contusion component to their injury.
      Timing of surgery seems to have very little effect on the final outcome.
      CONCLUSIONS: Final visual acuity is determined by the type and extent of trauma
      rather than the timing of surgery.

PMID- 8997594
TI  - Intraocular foreign bodies: myths and truths.
AB  - Over the centuries, the management of eyes with intraocular foreign bodies (IOFB)
      has posed a special challenge to the physician, and the anxiety created by such
      injuries has never abated. During the past few decades, several new diagnostic
      tests, IOFB removal techniques, and methods to treat the complications of the
      injury have been introduced. Nevertheless, old habits die hard: many of the
      management options that used to be standard are not appropriate any more but have
      proved difficult to change. This article reviews over forty of these die-hard
      myths and confronts them with factual statements published in the peer-review
      international literature.

PMID- 8997595
TI  - Dysplastic nevi are a risk factor for uveal melanoma.
AB  - Many studies have characterized the phenotypic features of individuals who are
      likely to develop cutaneous melanoma. One of the major items included in melanoma
      risk assessment has been the presence of clinically atypical nevi (dysplastic
      nevi). This study assessed the number of subjects with dysplastic nevi in groups
      of patients with uveal melanoma or cutaneous melanoma and in a group of volunteer
      controls. The SPSS program was used to calculate the odds ratios (hereafter
      called relative risks; RR) and 95% confidence intervals (C) in melanoma patients
      and controls. The RR was 4.36 for uveal melanoma (95% Cl 1.84-10.36) and 4.22 for
      cutaneous melanoma (95% Cl 1.81-9.84). These results suggest that cutaneous
      dysplastic nevi are a significant risk factor for uveal melanoma.

PMID- 8997596
TI  - Interferon alpha in the therapy of conjunctival lymphoma in an HIV+ patient.
AB  - The authors evaluated the efficacy of interferon-alpha used intralesionally in
      the therapy of low-grade conjunctival non-Hodgkin lymphoma in an HIV-positive
      patient. The patient received one intralesional injection of 1,000,000 U of
      interferon-alpha three times a week for a total of twelve doses. The remission of
      conjunctival involvement was seen three months from the end of therapy. The
      intralesional use of interferon-alpha can be considered an efficacious therapy
      for low-grade conjunctival non-Hodgkin lymphoma.

PMID- 8997597
TI  - Lacrimal sac dacryolith: a study wit atomic absorption spectrophotometry and
      scanning electron microscopy.
AB  - Dacryoliths are uncommon causes of partial or complete obstruction of the
      nasolacrimal drainage apparatus. We report our findings of a dacryolith that we
      studied by culture, light microscopy, atomic absorption spectrophotometry, and
      scanning electron microscopy. Although no fungi were recovered by culturing,
      hyphae-like structures were observed. No inorganic material was detected by
      atomic absorption spectrophotometry. Scanning electron microscopy of
      ultrastructure showed the stone was composed of lobes and lobules built on an
      amorphous core material.

PMID- 8997598
TI  - Evidence for dopamine 'D1-like' receptor subtypes in the behavioural effects of
      two new selective antagonists, LY 270411 and BW 737C.
AB  - A new, chemically distinct antagonist at dopamine 'D1-like' receptors, the
      thienoazepine LY 270411, ([+]-2(3-chloro-6-methyl-8-phenyl-5,6,7,8 -tetrahydro-4H
      thieno[2,3d]azepin-2-yl)propan-2-ol) was compared with the isoquinoline BW 737C
      ([S]-6-chloro-1-[2,5-dimethoxy-4- propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4
      tetrahydroisoquinoline) and the benzazepine SCH 23390 ([R]-7-chloro-8-hydroxy
      2,3,4,5-tetrahydro-3-methyl-1-phenyl-1 H-3-benzazepine) for effects on
      behavioural responses to the isochroman full efficacy dopamine 'D1-like' receptor
      agonist A 68930 ([1R,3S]-1-aminomethyl-5, 6-dihydroxy-3-phenylisochroman) vs. the
      dopamine 'D2-like' receptor agonist RU 24213 (N-n-propyl-N-phenylethyl-p-3
      hydroxyphenylethylamine). Grooming responses to A 68930 were readily blocked by
      each of LY 270411, BW 737C and SCH 23390; however, the vacuous chewing response
      was blocked only by BW 737C. Sniffing and locomotor responses to RU 24213 were
      attenuated by BW 737C and SCH 23390 but not by LY 270411; furthermore, myoclonic
      jerking to RU 24213 was released by BW 737C and SCH 23390 but not by LY 270411.
      These findings indicate that grooming induced by dopamine 'D1-like' receptor
      agonism is blocked by all chemical classes of dopamine 'D1-like' receptor
      antagonist while vacuous chewing is blocked only by isoquinoline dopamine 'D1
      like' receptor antagonism; this suggests that these behaviours may be mediated
      via functionally and pharmacologically distinct subtypes of dopamine 'D1-like'
      receptor. Furthermore, LY 270411 appears unique in its activity to readily block
      'D1-like' receptor agonist-induced grooming without influencing behavioural
      responses to dopamine 'D2-like' receptor agonism; thus, the site mediating
      prototypical dopamine 'D1-like' receptor agonist-induced behaviours may be
      dissociable pharmacologically from dopamine 'D1-like' site(s) participating in
      functional interactions with dopamine 'D2-like' receptors.

PMID- 8997600
TI  - Differential effects of agents acting at various sites of the NMDA receptor
      complex in a place preference conditioning model.
AB  - A conditioned place preference paradigm was used to assess the potential
      rewarding properties of the uncompetitive NMDA receptor antagonist, MK-801
      (dizolcipine), the two competitive NMDA receptor antagonists, CGP 37849 (DL-(E)-2
      amino-4-methyl-5-phosphono-3-pentonoic acid) and its (R)-enantiomer CGP 40116, as
      well as the partial agonist at strychnine-insensitive glycine receptors, ACPC (1
      aminocyclopropanecarboxylic acid). MK-801 (0.3 mg/kg), CGP 37849 (1.25-10 mg/kg)
      and CGP 40116 (1.25-10 mg/kg), administered in association with either the
      initially non-preferred or initially preferred side of the two-arm chamber,
      caused a significant increase in the time spent on that side in a post
      conditioning test. In contrast, ACPC did not support the conditioned place
      preference. Thus, the time spent on the drug-associated side following
      conditioning with ACPC (50-400 mg/kg) did not significantly differ from that
      measured in the pre-conditioning test, irrespective of whether it was associated
      with the initially non-preferred black side or the initially preferred white
      side. These results are consistent with both clinical and pre-clinical data
      demonstrating differences in psychopharmacological properties among compounds
      acting at the multiple, allosteric regulatory sites on the NMDA receptor complex.
      Moreover, these results indicate that the abuse potential of ACPC, which acts as
      a functional NMDA receptor antagonist, may be lower than that of either
      uncompetitive or competitive NMDA receptor antagonists.

PMID- 8997599
TI  - Hyperactivity and behavioral seizures in rodents following treatment with the
      dopamine D1 receptor agonists A-86929 and ABT-431.
AB  - A-86929 ((-)-trans-9,10-dihydroxy-2-propyl-4,5,5a,6,7,11b-hexahydro-3- thia-5
      azacyclopent-1-ena[c]phenanthrene) is a potent and selective full agonist at the
      dopamine D1 receptor. Both A-86929 and ABT-431 ((-)-trans-9,10-diacetyloxy-2
      propyl-4,5,5a,6,7,11b- hexahydro-3-thia-5-azacyclopent-1-ena[c]phenanthrene
      hydrochloride), the diacetyl prodrug derivative of A-86929, were evaluated for
      their effects on behavioral excitability in rodents. In rats, A-86929 produced a
      dose-dependent increase in locomotor activity that was attenuated by the
      selective dopamine D1 receptor antagonist, SCH 23390, as well as by higher doses
      of the dopamine D2 receptor antagonist, haloperidol. Repeated administration of A
      86929 over 6 days produced hyperactivity which did not change in magnitude across
      days. Acute administration of A-86929 and ABT-431 to mice produced behavioral
      seizure activity, with ED50 values of 7.1 and 2.7 mumol/kg, s.c., respectively,
      that was blocked by SCH 23390. Young rats (35-37 days) exhibited behavioral
      seizures following A-86929 and ABT-431 treatment (ED50 = 34.2 and 35.6 mumol/kg,
      s.c., respectively), but at doses higher than those required in mice. Moreover,
      adult rats (3 months) were less sensitive (ED50 = 345 mumol/kg, s.c.) to A-86929
      induced seizures than young rats. Comparison of the ED50 values that produced
      behavioral seizure activity in rats with those previously established to produce
      contralateral rotation (ED50 = 0.24 mumol/kg, s.c.) in 6-hydroxydopamine-lesioned
      rat indicates that a significant dose separation exists between these two
      properties of A-86929.

PMID- 8997601
TI  - Effects of galanin on 8-OH-DPAT induced decrease in body temperature and brain 5
      hydroxytryptamine metabolism in the mouse.
AB  - Central administration of galanin dose-dependently (minimum effective dose,
      M.E.D. = 1 nmol) blocked the hypothermia induced by the 5-HT1A receptor agonist 8
      hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg s.c.), in mice. This
      inhibitory effect was reversed by pretreatment with the galanin receptor
      antagonist galantide (0.3 nmol) and also by pretreatment with the ATP-sensitive
      potassium channel blockers glibenclamide (10 nmol) and gliquidone (10 nmol). The
      hypothermic response to 8-OH-DPAT was also blocked by the 5-HT1A receptor
      antagonist (N-(2,4(2-methoxyphenyl)-1-piperazinyl)ethyl-N-(2
      pyridinyl)cyclohexane, (WAY 100,635, M.E.D. = 0.01 mg/kg s.c.), and the centrally
      acting muscarinic receptor antagonist scopolamine (M.E.D. = 10 mg/kg i.p.) but
      not the peripheral muscarinic receptor antagonist N-methylscopolamine. 8-OH-DPAT
      (0.5 mg/kg s.c.) also decreased cortical and hypothalamic 5-HT (5
      hydroxytryptamine, serotonin) metabolism, an effect which was not blocked by
      pretreatment with galanin (0.3-3 nmol intracerebroventricular, i.c.v.). Neither
      did galanin (0.03-3 nmol/5 microliters i.c.v.) affect basal 5-HT metabolism in
      these brain regions. Furthermore, pretreatment in vitro of mouse cortical
      membranes with galanin (10 or 1000 nM) had no effect on 5-HT1A receptor affinity,
      Bmax or pharmacology determined using [3H]8-OH-DPAT. These results suggest that
      the inhibition of 8-OH-DPAT induced hypothermia by galanin is probably not
      mediated by an interaction with 5-HT1A receptors but more likely by blocking the
      indirect activation by 8-OH-DPAT of central cholinergic pathways involved in
      temperature regulation.

PMID- 8997602
TI  - Intrategmental infusion of cocaine decreases dopamine release and enhances
      norepinephrine release in the medial prefrontal cortex.
AB  - We evaluated the effects of local cocaine infusion into the A10 (ventral
      tegmental area), the cell body of the mesocorticolimbic dopaminergic pathway, on
      the extracellular concentrations of dopamine and norepinephrine in the medial
      prefrontal cortex, one of its terminal fields. A 1-ml Hamilton syringe was used
      to infuse a cocaine solution, either 20 or 200 microM, into the ventral tegmental
      area of anesthetized rats for 120 min through a microdialysis probe. The pure
      artificial cerebrospinal fluid (0 microM cocaine) infusion served as a control
      and a lidocaine (100 microM) infusion was administered to prevent the local
      anesthetic effect of cocaine. After intrategmental cocaine infusion (either 20 or
      200 microM), extracellular dopamine and norepinephrine in the ventral tegmental
      area both increased significantly to a steady state level (208 +/- 42 and 148 +/-
      23% for low dose and 220 +/- 24 and 150 +/- 15% for high dose). Simultaneously,
      the 200-microM cocaine infusion caused a significant decrease in extracellular
      dopamine (77 +/- 5%) but an increase in norepinephrine (140 +/- 6%) in the medial
      prefrontal cortex. The local anesthetic, lidocaine, produced no effects on the
      dopamine or norepinephrine output (neither in the ventral tegmental area nor in
      the medial prefrontal cortex). This study not only supports recent findings of an
      increase in extracellular dopamine and norepinephrine in the ventral tegmental
      area on intrategmental cocaine infusion, but also demonstrates that cocaine
      infused locally in the ventral tegmental area can decrease dopamine and increase
      norepinephrine at a remote terminal area (medial prefrontal cortex). Finally, the
      introduction rate of cocaine into the ventral tegmental area by retrograde
      microdialysis was found to be 0.83 ng/min for the low dose and 8.14 ng/min for
      the high dose.

PMID- 8997603
TI  - The contribution of adenosine to paired-pulse inhibition in the normal and
      disinhibited hippocampal slice.
AB  - The effects of the adenosine receptor antagonist 1,3-dimethyl-8
      cyclopentylxanthine (cyclopentyltheophylline) and the enzyme adenosine deaminase
      have been examined on paired-pulse inhibition between orthodromic evoked field
      potentials in the CA1 region of the normal and disinhibited hippocampal slice. In
      the presence of the GABAA receptor antagonist (-)-bicuculline methobromide,
      cyclopentyltheophylline suppressed homosynaptic paired-pulse inhibition between
      stimuli 300 ms apart. Slices treated with (-)-bicuculline and
      cyclopentyltheophylline together tended to develop spontaneous burst potentials.
      In slices in which a surgical cut isolated the CA1 and CA3 areas, thereby
      preventing the development of bursts in CA1, the effect on paired-pulse
      inhibition was lessened but was still apparent. Adenosine deaminase, in the
      presence of (-)-bicuculline showed the same effect as cyclopentyltheophylline,
      decreasing substantially the amount of paired-pulse inhibition. These results
      suggest that adenosine may contribute to homosynaptic paired-pulse inhibition in
      disinhibited slices. For comparison, we also examined the effect of
      cyclopentyltheophylline in normal ((-)-bicuculline-free) slices. At 100 nM,
      cyclopentyltheophylline increased reversibly the size of orthodromically evoked
      synaptic population potentials in the CA1 region of the slices and also reduced
      reversibly the degree of homosynaptic paired-pulse inhibition between two stimuli
      delivered only 30 ms apart. This suggests that adenosine may also contribute to
      shorter latency paired-pulse inhibition in the normal hippocampal slice.

PMID- 8997605
TI  - Reduction of dopamine release and synthesis by repeated amphetamine treatment:
      role in behavioral sensitization.
AB  - Changes in extracellular dopamine concentration in the ventral striatum during
      repeated amphetamine administration and over the first 7 days of withdrawal were
      studied by transversal microdialysis in freely moving rats. 2 days after fiber
      implantation rats were treated with either amphetamine (1.5 mg/kg i.p.) or saline
      every 12 h for 14 days. In amphetamine-treated rats, the baseline extracellular
      dopamine concentration, preceding the morning treatment, increased from 0.43 +/-
      0.01 on day 1 up to 0.59 +/- 0.02 pmol/40 microliters sample on day 3 of
      treatment. Thereafter, dopamine fell rapidly on day 5(0.16 +/- 0.01 pmol/40
      microliters) and remained at approximately the level reached on day 7(0.11 +/-
      0.01 pmol/40 microliters) throughout the treatment and also over the 7 days of
      withdrawal. In contrast, in control rats, the extracellular dopamine
      concentration (0.40 +/- 0.01 pmol/40 microliters, on day 1) decreased
      progressively during the first days of treatment to reach a fairly stable value
      on day 4 (0.25 +/- 0.01 pmol/40 microliters sample). Thereafter, dopamine
      remained stable at this level throughout the remaining period of experimentation.
      Challenge with amphetamine (1.5 mg/kg i.p.) of animals treated with amphetamine
      for 10 days or withdrawn for 7 days produced a potentiated motor response
      compared to that in control rats but much less marked dopamine releasing effects.
      Dopamine synthesis in the ventral striatum, measured as L-dihydroxyphenylalanine
      formation after blockade of dihydroxyphenylalanine decarboxylase, was found to be
      reduced by approximately 60% after 2 weeks of amphetamine treatment and in
      animals withdrawn for 1 day or 7 days. These results indicate that repeated
      amphetamine treatment causes persistent inhibition of dopamine synthesis and
      release in the ventral striatum. Such inhibition may be a compensatory response
      to the repeated stimulation of postsynaptic dopamine receptors by the
      endogenously released dopamine and also the cause of postsynaptic sensitization
      to dopamine action.

PMID- 8997604
TI  - Piroxicam modifies the effects of ethanol on isolated rat hepatocytes.
AB  - It has been reported that piroxicam prevents the hepatic increase of
      triacylglycerides and thiobarbituric acid-reactive substances observed after
      acute ethanol intoxication in rats and also causes a decrease in blood ethanol
      concentration. The aim of this study was to assess the effect of piroxicam on
      these 3 metabolic indicators, using isolated rat hepatocytes incubated with
      ethanol or lactate, supplemented or not with epinephrine. Epinephrine stimulated
      the consumption of lactate, but not of ethanol. In the isolated hepatocytes, and
      in a dose-dependent fashion, piroxicam alone raised the consumption of lactate
      and ethanol, increased the triacylglyceride pool in cells incubated with lactate
      or ethanol, and decreased the content of thiobarbituric acid-reactive substances
      in cells incubated with ethanol, but not with lactate. Epinephrine blocked these
      actions of piroxicam, except the lowering of the content of thiobarbituric acid
      reactive substances. Thus, piroxicam helps to control the oxidative stress
      produced in isolated hepatocytes by ethanol.

PMID- 8997606
TI  - Repeated treatment with adenosine A1 receptor agonist and antagonist modifies the
      anticonvulsant properties of CPPene.
AB  - The effects of repeated administration of the selective adenosine A1 receptor
      agonist 2-chloro-N6-cyclopentyladenosine (CCPA), the selective adenosine A2
      receptor agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA), the non
      selective adenosine A1/A2 receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA),
      the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3 dipropylxanthine
      (DPCPX) and the selective adenosine A2 receptor antagonist 5-amino-7-(2
      phenylethyl)-2-(2-furyl)-pyrazolo-(4,3-e)1,2,4-triazolo(1,5 -c)pyrimidine (SCH
      58261) on the anticonvulsant activity of 3-(2-carboxypiperazine-4y)propenyl-1
      phosphonic acid (CPPene), a selective N-methyl-D-aspartate receptor antagonist,
      were evaluated in audiogenic sensible dilute brown agouti mice DBA/2J (DBA/2).
      Mice were treated intraperitoneally twice daily for 7 days with CCPA 0.11 mg/kg,
      2HE-NECA 0.056 mg/kg, NECA 0.11 mg/kg, DPCPX 0.5 mg/kg and SCH 58261 0.5 mg/kg
      followed by 2 vehicle injections (the wash-out period of 1 day) and subsequently
      CPPene was administered intracerebroventricularly. Audiogenic seizures were
      delivered 30 min after CPPene administration. Repeated treatment with CCPA
      significantly reduced the anticonvulsant properties of CPPene against audiogenic
      seizures. A weak and not significant reduction of anticonvulsant effects of
      CPPene was observed following repeated administration of NECA, whilst the
      repeated administration of 2HE-NECA did not decrease the antiseizure activity of
      CPPene. Conversely, repeated administration of DPCPX markedly potentiated the
      anticonvulsant properties of CPPene, whilst the repeated treatment with SCH 58261
      did not increase the anticonvulsant activity of CPPene. The present results
      indicate that repeated treatment with CPPA, a selective adenosine A1 receptor
      agonist, decreases the anticonvulsant properties of CPPene, whilst the repeated
      administration of DPCPX, a selective adenosine A1 receptor antagonist,
      potentiates the anticonvulsant effects of CPPene. The compounds acting as
      selective agonists or antagonists of adenosine A2 receptors do not affect the
      antiseizure activity of CPPene. In conclusion, the repeated interaction of
      agonists or antagonists with adenosine A1 receptors seems to induce changes on
      anticonvulsant activity of CPPene, whereas drugs acting at adenosine A2 receptors
      do not.

PMID- 8997607
TI  - Intranigral or intrastriatal injections of GDNF: effects on monoamine levels and
      behavior in rats.
AB  - The present studies were designed to determine whether administration of
      recombinant human glial cell line-derived neurotrophic factor (rhGDNF) into
      either the substantia nigra or striatum is capable of augmenting dopamine
      function of the nigrostriatal pathway in normal rats. Single bolus intracranial
      injections of rhGDNF at either site increased locomotor activity and decreased
      food and water consumption and body weight in a dose-dependent manner when
      compared to vehicle-treated animals. These behavioral responses returned to pre
      control levels within 3 weeks post rhGDNF administration. Administration of
      rhGDNF intranigrally increased dopamine, dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA) levels of the ipsilateral substantia nigra at 2 and 6
      weeks post injection but had no augmenting effects on dopamine or its metabolites
      in the striatum. Administration of rhGDNF intrastriatally increased DOPAC and HVA
      levels of the ipsilateral striatum, although striatal dopamine levels were
      unchanged. Ipsilateral nigral dopamine levels were increased after intrastriatal
      injection of rhGDNF. The effects of intracranial rhGDNF were not specific to the
      nigrostriatal dopamine system, since nigrostriatal serotonin, 5
      hydroxyindoleacetic acid (5-HIAA), epinephrine and norepinephrine transmitter
      levels were altered depending on administration route for rhGDNF and dose. Taken
      together, these data demonstrate long-lasting neurochemical and behavioral
      changes which suggest that rhGDNF can augment function in adult rat dopamine
      neurons. Therefore, rhGDNF may have therapeutic potential for Parkinson's
      disease.

PMID- 8997608
TI  - Spontaneous release of acetylcholine in striatum is preferentially regulated by
      inhibitory dopamine D2 receptors.
AB  - The dose-related effects of the direct dopamine D2 receptor agonist quinpirole
      [trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1 H-pyrazolo[3,4-g]quinoline]
      on the extracellular concentrations of dopamine and acetylcholine in rat striatum
      were measured using in vivo microdialysis. Quinpirole was administered
      intraperitoneally at doses of 3, 30, 300, and 3000 micrograms/kg. Acetylcholine
      measurements were conducted in the presence of 10 nmol/l of the
      acetylcholinesterase inhibitor neostigmine in the microdialysis perfusate. The 3
      micrograms/kg dose of quinpirole elicited a significant 26% decrease in
      extracellular dopamine level in striatum whereas the extracellular level of
      acetylcholine was significantly increased by 15%. At the higher doses tested,
      quinpirole administration produced significant decreases in the extracellular
      concentrations of both dopamine and acetylcholine. The maximum inhibition of
      striatal dopamine efflux by quinpirole was 74% and this effect was observed at
      the 300 micrograms/kg dose. Inhibition of striatal acetylcholine output reached a
      maximum of 78% after administration of 3000 micrograms/kg quinpirole. ED50 values
      (microgram/kg) for quinpirole-induced inhibition of release were 12.4 and 240 for
      striatal dopamine and acetylcholine, respectively. We conclude from these data
      that dopamine exerts a tonic inhibitory control over spontaneous acetylcholine
      efflux in striatum that is directly mediated by dopamine D2 receptors.

PMID- 8997609
TI  - Vesicular dysfunction during experimental thiamine deficiency is indicated by
      alterations in dopamine metabolism.
AB  - Experimental and clinical studies indicate that catecholamines play an important
      role in the neurobehavioural symptomatology of thiamine deficiency. Given the
      cerebral region-selective vulnerability and the behavioural impairment commonly
      encountered in thiamine deficiency, we undertook to investigate regional
      catecholamine metabolism in the brains of pyrithiamine-induced thiamine-deficient
      rats. Dopamine metabolism was unaffected in the striatum. In contrast, other
      regions also known to be involved in sensory processing and intellectual function
      (e.g., frontal cortex, hypothalamus, thalamus), but having a greater
      noradrenergic input, had increased levels of 3,4-dihydroxyphenylacetic acid
      (DOPAC) and decreased levels of other dopaminergic metabolites including
      noradrenaline. In these regions levels of the vesicular amine transporter,
      defined by tetrabenazine-sensitive [3H]ketanserin binding, were also decreased.
      Our data suggest a region-selective vesicular dysfunction resulting in
      intraneuronal release, and subsequent degradation, of dopamine. These disruptions
      of dopamine and consequently noradrenaline metabolism may account for certain
      neurobehavioural deficits commonly encountered in thiamine deficiency.

PMID- 8997611
TI  - Innervation and nitric oxide modulation of mesenteric arteries of the golden
      hamster.
AB  - Immunohistochemical and pharmacological techniques were used to examine
      perivascular nerves, endothelium and the effects of inhibition of nitric oxide
      synthesis on responses in mesenteric arteries/perfused mesenteric arterial beds
      of the Golden hamster. Frequency-dependent vasoconstrictions to electrical field
      stimulation and dose-dependent vasoconstrictions to noradrenaline were
      significantly augmented by NG-nitro-L-arginine methyl ester (10(-5) M), an
      inhibitor of nitric oxide synthase. In preparations with tone raised with
      methoxamine (10 microM) dose-dependent relaxations to ATP, but not to
      acetylcholine, were blocked by NG-nitro-L-arginine methyl ester. In the presence
      of guanethidine (5 microM) to block sympathetic neurotransmission there was no
      neurogenic relaxation to electrical field stimulation. Furthermore, the sensory
      neurotoxin capsaicin (0.05-5 nmol) did not elicit relaxation. Immunohistochemical
      studies demonstrated dense plexuses of fibres immunoreactive for tyrosine
      hydroxylase and neuropeptide Y, a plexus of moderate density for calcitionin gene
      related peptide and an absence of fibres immunoreactive for substance P and
      vasoactive intestinal polypeptide. Of particular interest is the finding that
      whereas sympathetic perivascular nerves and nitric oxide regulate the function of
      hamster mesenteric arteries, there is no apparent motor function of calcitonin
      gene-related peptide-containing sensory nerves.

PMID- 8997610
TI  - Intravascular substance P dilates cerebral parenchymal vessels through a specific
      tachykinin NK1 receptor in cats.
AB  - The role of substance P in the cerebral parenchymal circulation was examined in
      19 anesthetized cats. The local cerebral blood volume in the temporoparietal
      cortex was measured by our photoelectric method. Cerebral blood volume reflects
      the cumulative dimensions of the parenchymal microvessels. Intravenous injection
      of 0.01, 0.1, and 1 mg/kg FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)
      carbonyl-L-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide) , a
      selective tachykinin NK1 receptor antagonist, had no significant effects
      (compared to the vehicle, ethanol) on cerebral blood volume and mean arterial
      blood pressure. Intracarotid injection of 1, 10, 100 pmol/kg, and 1 nmol/kg
      substance P increased cerebral blood volume (P < 0.01) in a dose-dependent manner
      (maximal increase of 6.5% at 5 min). Following injection of 1 nmol/kg substance
      P, cerebral blood volume was initially reduced, possibly due to the marked fall
      in mean arterial blood pressure (P < 0.01). The cerebral blood volume increase
      elicited by 1 nmol/kg substance P was strongly blocked (P < 0.05) by prior
      injection of 1 mg/kg FK888. However, the depressor effect of 1 nmol/kg substance
      P (-24 +/- 4 mm Hg at 30 s, P < 0.01) was partially inhibited (P < 0.01) by
      FK888. We conclude that endogenous substance P may not have a significant role in
      the maintenance of resting tone of cerebral parenchymal vessels. Intravascular
      substance P, however, dilates the small microvessels through a specific
      tachykinin NK1 receptor and could be involved in the development of pathologic
      processes such as migraine headache.

PMID- 8997612
TI  - In vivo inhibition of nitric oxide synthesis does not depend on renin-angiotensin
      system activation.
AB  - The role of the renin-angiotensin system in the haemodynamic changes induced by
      acute administration of N omega-nitro-L-arginine methyl ester in anaesthetised
      dogs was investigated. The left femoral artery and vein were cannulated for blood
      pressure measurement and drug administration, respectively. A Swan-Ganz catheter
      was introduced through the right femoral vein and advanced to the pulmonary
      artery. Pulmonary arterial pressure, right atrial pressure and cardiac output
      were also determined. N omega-Nitro-L-arginine methyl ester (0.01-10.0 mg/kg) was
      administered alone (control animals, n = 18) or in the presence of the
      angiotensin-converting enzyme inhibitors, captopril (2 mg/kg, n = 9) or enalapril
      (2 mg/kg, n = 7) or of the bradykinin B2 receptor antagonist D-[Arg-Hyp3, Thi5, D
      Tic7, Oic8]bradykinin (Hoe 140, 0.1 mg/kg, n = 6). Cerebellum nitric oxide
      synthase and serum angiotensin-converting enzyme activities were also measured. N
      omega-Nitro-L-arginine methyl ester induced dose-dependent increases in blood
      pressure and systemic vascular resistance and decreases in heart rate and cardiac
      output. Nitric oxide synthase activity was inhibited 58% by N omega-nitro-L
      arginine methyl ester (from 3.37 +/- 0.30 to 1.40 +/- 0.24 pmol/min per mg
      protein, P < 0.05, n = 5). Both enalapril and captopril potentiated the
      cardiovascular changes induced by bradykinin (300 ng/kg, bolus). Moreover,
      enalapril inhibited angiotensin-converting enzyme activity from 12.8 +/- 1.2 to
      1.1 +/- 0.2 nmol/ml per min (P < 0.05, n = 6). Under these conditions, N omega
      nitro-L-arginine methyl ester administration elicited the same haemodynamic
      changes as those observed in non-treated animals, except for preventing the
      decrease in systolic index. Hoe 140 had no effect on the cardiovascular responses
      to N omega-nitro-L-arginine methyl ester. These results indicate that the renin
      angiotensin system does not modulate these haemodynamic changes.

PMID- 8997613
TI  - Y-26763 protects the working rat myocardium from ischemia/reperfusion injury
      through opening of KATP channels.
AB  - This investigation was undertaken to determine the possible protection against
      ischemia afforded by Y-26763, [(-)-(3S,4R)-4-(N- acetyl-N-hydroxyamino)-6-cyano
      3,4-dihydro-2,2-dimethyl-2H-1-benzopyran- 3- ol], which has K+ channel-opening
      properties, in isolated rat hearts under working conditions. This preparation was
      subjected to 28 min of global ischemia followed by 30 min of reperfusion. Drugs
      were injected into the aortic cannula prior to ischemia. Compared to control, Y
      26763 (1 microM) resulted in a significant recovery of post-ischemic cardiac
      functions, significant reduction of cellular enzyme loss, and preserved
      significantly the stocks of cellular high-energy phosphates and the myocyte
      ultrastructure. These effects of Y-26763 were completely prevented by
      glibenclamide (10 microM), a specific K+ channel blocker of KATP channels. In non
      ischemic conditions, Y-26763 significantly increased coronary flow without
      affecting cardiac output and heart rate. The data were analyzed statistically by
      analysis of variance. The results clearly demonstrate that Y-26763 protects the
      myocardium from ischemic injury by opening KATP channels.

PMID- 8997615
TI  - Antiarrhythmic effects of HOE642, a novel Na(+)-H+ exchange inhibitor, on
      ventricular arrhythmias in animal hearts.
AB  - HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate), a
      novel Na(+)-H+ exchange subtype 1 inhibitor, was investigated for its possible
      antiarrhythmic effects on coronary artery ligation/reperfusion and ouabain
      induced arrhythmias in the canine heart which may occur after intracellular Ca2+
      overload. Also, the effects of HOE642 on coronary artery ligation/reperfusion of
      the left coronary artery were tested in rat hearts. HOE642 (1 mg/kg)
      significantly suppressed the occurrence of fatal ventricular fibrillation during
      coronary artery ligation and after reperfusion in dogs (2 out of 8 dogs in the
      treated group compared to 7 out of 8 dogs in the control group, P < 0.05), but
      did not suppress ventricular premature contractions and ventricular tachycardia
      during ischemia in the canine hearts. HOE642 at the same dose markedly reduced
      the total duration and the incidence of reperfusion-induced ventricular
      tachycardia, and the incidence and mortality of reperfusion-induced ventricular
      fibrillation in rats (ventricular tachycardia duration, 159 +/- 12 s to 21 +/- 8
      s, P < 0.01; ventricular tachycardia, 100% to 69%; ventricular fibrillation, 89%
      to 0%, P < 0.01; mortality, 89% to 11%, P < 0.01). The heart rate, blood
      pressure, QT interval and ST segment did not change in the canine and rat hearts.
      HOE642 slightly decreased the arrhythmic ratio of the ouabain-induced arrhythmia
      only at two time points (28 and 35 min after injection) in the canine hearts. In
      conclusion, HOE642 has obvious antifibrillatory effects on ischemia/reperfusion
      arrhythmias and, in addition, has a weak suppressing effect on the ouabain
      induced arrhythmia.

PMID- 8997614
TI  - The role of brain acetylcholine in GABAA receptor antagonist-induced blood
      pressure changes in rat.
AB  - Previous experimental studies have shown that intracerebroventricular (i.c.v.)
      injection of the GABAA receptor antagonist, bicuculline methiodide, results in
      marked increases in blood pressure due to an increase in sympathetic nervous
      system activity. It is well recognized that the central cholinergic system is
      also involved in the regulation of blood pressure. In the present study, we
      examined the role of brain acetylcholine in the pressor response induced by
      bicuculline methiodide in conscious Sprague-Dawley rats. I.c.v. (0.05, 0.3 and
      0.5 nmol) and intrahypothalamic (40 pmol) administration of bicuculline
      methiodide produced blood-pressure increases in a dose-dependent manner.
      Hemicholinium-3 was given i.c.v. 1 h prior to bicuculline methiodide. The
      depletion of brain acetylcholine was demonstrated by the suppression of
      physostigmine-induced pressor responses, but blood pressure increases in response
      to carbachol remained unchanged. The pressor responses to bicuculline methiodide
      in animals pre-treated with hemicholinium-3 were significantly higher than those
      seen in saline-pre-treated groups. Likewise, bicuculline methiodide, at a dose
      that did not alter blood pressure alone, caused pressor responses in rats pre
      treated with the nicotinic receptor antagonist, mecamylamine, whereas the
      muscarinic receptor antagonist, atropine, was ineffective in this respect. In
      conclusion, it seems likely that endogenous brain acetylcholine has a modulator
      role on GABAA receptor-mediated blood-pressure control via nicotinic receptors.

PMID- 8997616
TI  - Short-term oral administration of L-arginine reverses defective endothelium
      dependent relaxation and cGMP generation in diabetes.
AB  - In the present study, we evaluated whether acute dietary supplementation with L
      arginine in vivo could reverse the defective endothelium-dependent relaxation in
      diabetic blood vessels assessed ex vivo. At 8 weeks of diabetes, streptozotocin
      induced diabetic rats were given 1.25% L-arginine in drinking water 3 days prior
      to isolation of aortic rings for evaluation ex vivo. Plasma arginine
      concentration was reduced by diabetes but restored to normal in diabetic rats
      receiving dietary L-arginine. In norepinephrine-contracted rings, relaxation to
      acetylcholine but not to nitroglycerin was reduced by diabetes. Dietary treatment
      with L-arginine restored relaxation to acetylcholine without altering relaxation
      to nitroglycerin and restored the defect in acetylcholine-stimulated cGMP
      generation. These data suggest that the substrate for nitric oxide synthesis by
      the endothelium is likely to be limited in diabetes but can be overcome by
      dietary supplementation with L-arginine.

PMID- 8997617
TI  - Differential ontogeny of adenosine receptors in the longitudinal muscle and
      muscularis mucosae of the rat isolated duodenum.
AB  - The ontogeny of P1 purinoceptors in the separated layers of the rat duodenum was
      investigated using functional assays. In the longitudinal muscle N6
      cyclopentyladenosine (CPA) caused relaxations from day 20 that were inhibited by
      1,3-dipropyl-8-cyclopentyl-xanthine (DPCPX) (10 nM) indicating an action via
      adenosine A1 receptors. 5'-N-ethylcarboxamidoadenosine (NECA) caused relaxations
      at day 15 that were inhibited by DPCPX (1 microM) while 2-p-(2
      carboxyethl)phenylethylamino-5'-N-ethylcarboxamidoade nosine (CGS 21680) was
      almost inactive, indicating an action at adenosine A2B receptors. From day 20
      NECA was inhibited by DPCPX (10 nM) but was not antagonised by DPCPX (1 microM)
      to the extent expected for an adenosine A1 receptor, suggesting activation of
      adenosine A1 and adenosine A2B receptors. In the muscularis mucosae, CPA and NECA
      caused contractions from day 10 inhibited by DPCPX (1 microM) while CGS 21680 was
      less potent, indicating activation of adenosine A2B receptors. These results show
      that adenosine A2B receptors are present early in the postnatal period, whereas
      adenosine A1 receptors develop after day 20.

PMID- 8997618
TI  - The effects of cetiedil and its congeners on levcromakalim-stimulated 86Rb efflux
      from smooth and skeletal muscle.
AB  - The effects of cetiedil on levcromakalim-stimulated 86Rb efflux from rat aorta,
      rat anococcygeus and frog sartorius muscle have been investigated. In experiments
      on rat aorta, cetiedil inhibited the tracer efflux stimulated by 10 microM
      levcromakalim with an IC50 of 1.3 +/- 0.4 microM. In the rat anococcygeus and
      frog sartorius 10 microM cetiedil caused 67 +/- 11% and 84 +/- 4% inhibition of
      the responses to 10 microM and 50 microM levcromakalim respectively. The effect
      of two analogues of cetiedil, UCL 1285 (cetiedil methiodide) and UCL 1495
      (triphenyl acetic acid-2-N[5-ethyl-2-methylpiperidinoethyl] ester) were also
      tested on rat aorta. UCL 1285 caused inhibition of the response to 10 microM
      levcromakalim with an IC50 of approximately 6 microM. In contrast, UCL 1495 (10
      microM) had no significant effect. It is concluded that cetiedil is an effective
      blocker of the action of levcromakalim in smooth and skeletal muscle but does not
      distinguish between tissues. The relative activities of cetiedil, UCL 1285 and
      UCL 1495 are discussed in relation to their activity at other cetiedil-sensitive
      K+ channels.

PMID- 8997619
TI  - Nitric oxide regulation of TP receptor-mediated pulmonary vasoconstriction in the
      anesthetized, open-chest rat.
AB  - We investigated the influence of endothelial nitric oxide (NO) on the pulmonary
      pressor activity of the stable thromboxane A2 analogue, U-46619 (9,11-dideoxy-9
      alpha-(methanoepoxy) prostaglandin F2 alpha), in anesthetized open-chest Sprague
      Dawley rats (n = 6-9 per group). NO synthase inhibition, as obtained by N omega
      nitro-L-arginine methyl ester (L-NAME; 0.63 mg/kg i.v. + 20 mg/kg/h), induced
      sustained systemic hypertension (mean maximal increase, delta, in mean systemic
      arterial pressure = 38 +/- 6 mmHg; P < 0.05 vs. vehicle) associated with slight
      bradycardia (delta heart rate = -42 +/- 8 beats/min; P < 0.05 vs. vehicle) and
      delayed- (> 30 min) onset pulmonary hypertension (delta mean pulmonary arterial
      pressure = 10 +/- 3.4 mmHg; P < 0.05 vs. vehicle). In separate experiments, when
      mean systemic arterial pressure was maximally increased by L-NAME, the difference
      between mean pulmonary arterial pressure and mean left atrial pressure was
      greater in L-NAME-treated rats (41 +/- 16% compared to 10 +/- 1% in the vehicle
      group; P < 0.05), strongly suggesting that spontaneously released NO modulated
      pulmonary vascular resistance. L-Arginine at a dose which reduced by
      approximately 50% the L-NAME-associated systemic hypertension did not alter the
      late rise in mean pulmonary arterial pressure (delta mean pulmonary arterial
      pressure = 12 +/- 4 mmHg; P = NS vs. L-NAME alone). U-46619, elicited rapid, dose
      dependent, and transient increases in mean pulmonary arterial pressure (delta =
      8.8 +/- 2.0 and 21.2 +/- 1.9 mmHg at 1.25 and 20 micrograms/kg i.v. respectively;
      both P < 0.01 vs. vehicle). U-46619 (1.25 micrograms/kg)-induced increases in
      mean pulmonary arterial pressure were fully antagonized by the thromboxane
      A2/prostanoid (TP) receptor antagonist, SQ 29,548 ([1S-[1 alpha,2 alpha(5Z),3
      alpha,4 alpha]]-7-[3-[[2-[(phenyl-amino)-carbonyl] hydrazino] methyl]-7
      oxabicyclo [2.2.1]hept-2-yl]-5-heptenoic acid) (0.63 mg/kg i.v. + 0.63 mg/kg/h).
      Injection of U-46619 (1.25 micrograms/kg), 15 min after L-NAME administration,
      evoked a 24.7 +/- 0.9 mmHg increase in mean pulmonary arterial pressure (P < 0.01
      vs. U-46619 in control rats), which was (i) greater than that produced by a 16
      fold higher dose of U-46619 alone, (ii) fully antagonized by SQ 29,548, (iii)
      significantly attenuated during coadministration of L-NAME and L-arginine (10
      mg/kg i.v. + 160 mg/kg/h; delta mean pulmonary arterial pressure = 14.6 +/- 4.3
      mmHg; P < 0.05 vs. U-46619 following L-NAME alone and P = NS vs. U-46619 in
      control rats). These results indicate that, under normal circumstances, pulmonary
      vasomotor tone is regulated by spontaneously released NO. Moreover, pulmonary
      vascular NO attenuates TP receptor-mediated pressor responses, strongly
      suggesting that in addition to mediating pulmonary vasoconstriction, TP receptor
      activation also concomitantly releases NO within the pulmonary vasculature.

PMID- 8997620
TI  - Eosinophils and neutrophils modify arachidonic acid-induced relaxation of guinea
      pig trachea.
AB  - The influence of inflammatory cells on airway reactivity was investigated on
      arachidonic acid-induced relaxations of guinea-pig trachea and on arachidonic
      acid metabolism in guinea-pig tracheal epithelial cells. The presence of either
      eosinophils or neutrophils (1.0 x 10(7) cells/ml), from bronchoalveolar lavage,
      decreased the tracheal relaxations induced by arachidonic acid (1.0-30 microM).
      The basal synthesis of prostaglandin E2 was increased in epithelial cells (from
      176 +/- 36 to 7920 +/- 898 pg/ml), eosinophils (from 360 +/- 56 to 2693 +/- 686
      pg/ml) and neutrophils (from 352 +/- 81 to 4400 +/- 272 pg/ml) following
      incubation with arachidonic acid (10 microM). The co-incubation of either
      eosinophils or neutrophils with epithelial cells, in the presence of arachidonic
      acid, decreased the synthesis of prostaglandin E2 (2600 +/- 686 and 4400 +/- 272
      pg/ml respectively) but increased the synthesis of thromboxane B2 (from 60 +/- 6
      to 11634 +/- 840 and 9282 +/- 485 pg/ml respectively). Similarly, when major
      basic protein-treated (100 micrograms/ml) epithelial cells were incubated with
      arachidonic acid, the prostaglandin E2 synthesis decreased (75%) but thromboxane
      B2 synthesis was unaffected. The results suggest that eosinophils and neutrophils
      may impair arachidonic acid metabolism in guinea-pig epithelium in favor of
      production of bronchoconstrictor prostanoids.

PMID- 8997621
TI  - Investigation of 5-HT3 receptor-mediated contraction in guinea-pig distal colon.
AB  - We investigated the participation of cholinergic and tachykininergic mechanisms
      in 5-hydroxytryptamine (5-HT)-induced contraction via 5-HT3 receptors in
      longitudinal and circular muscle of guinea-pig isolated distal colon. 5-HT
      produced concentration-dependent contractile responses in longitudinal and
      circular muscle. The 5-HT3 receptor antagonists ramosetron (YM060) ((R)-5-[(1
      methyl-3-indolyl) carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride),
      YM114 (KAE-393) ((R)-5-[(2,3-dihydro-1-indolyl)carbonyl]-4,5,6,7-tetrahydro-1 H
      benzimidazole hydrochloride), ondansetron and granisetron produced a
      concentration-dependent shift to the right of the 5-HT concentration-response
      curves in both muscle. However, methysergide and GR113808 had no effect on 5-HT
      induced contraction. In the longitudinal muscle, atropine concentration
      dependently inhibited 5-HT-induced contraction, and tetrodotoxin abolished it.
      (+/-)-CP96,345 attenuated the contractile response to 5-HT, but (+/-)-SR48,968
      had no effect on it. In the presence of atropine, (+/-)-CP96,345 completely
      blocked 5-HT-induced contraction. In the circular muscle, atropine had no effect
      on the contractile response to 5-HT, whereas tetrodotoxin completely suppressed
      it. The contractile response elicited by 5-HT in the circular muscle was not
      inhibited by either (+/-)-CP96,345, (+/-)-SR48,968, devazepide, L-365,260 or
      indomethacin. It is suggested that 5-HT acts via 5-HT3 receptors to release
      acetylcholine and substance P, which in turn are responsible for contraction of
      the longitudinal muscle. In the circular muscle, as in the longitudinal muscle, 5
      HT-induced contraction is mediated by the 5-HT3 receptor. Unlike the case in
      longitudinal muscle, however, this contraction involves neither cholinergic nor
      tachykininergic transmission. It is also suggested that neither cholecystokinin
      (CCK) nor prostaglandins participate in 5-HT3 receptor-mediated contraction in
      circular muscle.

PMID- 8997622
TI  - Characterisation of a novel airway late phase model in the sensitized guinea pig
      which uses silica and Bordetella pertussis as adjuvant for sensitization.
AB  - The objective of the present investigation was to validate a novel model of
      allergic late phase reaction in the airways of conscious guinea pigs by
      monitoring airway function with CO2-forced respiration. In addition airway
      inflammation as one possible cause for the development of airway late phase
      reaction was characterized by a novel technique which consists of bronchoalveolar
      lavage via the orotracheal route. Guinea pigs were sensitized twice at 2-week
      intervals with ovalbumin in silica and Bordetella pertussis. Two weeks after the
      booster sensitization all guinea pigs showed an acute decrease of tidal volume
      under CO2-forced respiration 5-15 min after antigen challenge. In contrast 42 out
      of 68 (= 62%) screened guinea pigs exhibited airway late phase response between 4
      10 h after aerosol antigen challenge. During a subsequent cross-over study
      methylprednisolone (twice at 16 and 1 h before ovalbumin) did not significantly
      interfere with the acute response. In contrast the airway late phase response as
      well the associated eosinophil influx into the bronchoalveolar lavage were
      attenuated by the steroid. In conclusion, the sensitization procedure in
      combination with the novel method for monitoring airway function allowed
      measurement of a reproducible airway late phase response in about 60% of
      sensitized guinea pigs. The sensitivity of exclusively the late phase response
      and eosinophil influx to treatment with a glucocorticoid not only correlates this
      model with clinical pharmacotherapy but also strengthens the inflammatory nature
      of this model.

PMID- 8997623
TI  - Mechanism of inhibition of tumor necrosis factor production by chlorpromazine and
      its derivatives in mice.
AB  - In previous work, we reported that chlorpromazine inhibits tumor necrosis factor
      (TNF) production in endotoxin lipopolysaccharide-treated mice, and protects
      against lipopolysaccharide toxicity. Chlorpromazine is used as an antipsychotic
      and has several effects on the central nervous system. It acts on different
      neurotransmitter receptors and has other biochemical activities some of which,
      like inhibition of phospholipase A2, might be responsible for the inhibitory
      effect on TNF production. To investigate the role of these actions in the
      inhibition of TNF production by chlorpromazine, we have synthesized some
      chlorpromazine derivatives that do not have central activities. Some of these
      analogs have lost their affinity for various receptors and their phospholipase A2
      inhibitory activity, but still inhibit TNF production. No correlation was found
      between TNF inhibition and the ability to inhibit nitric oxide (NO) synthase,
      whereas a good correlation was evident between TNF inhibition and antioxidant
      activity.

PMID- 8997624
TI  - Study of potency, kinetics of block and toxicity of NMDA receptor antagonists
      using fura-2.
AB  - NMDA receptor antagonists reduced NMDA-triggered increases in [Ca2+]i measured by
      fura-2 and showed qualitative differences in the potency and kinetics of block.
      High potency antagonists produced a slow block which allowed an initial increase
      in [Ca2+]i that was greater than the steady-state level, while compounds with
      moderate to low potency produced a rapid block that was at steady-state from the
      first measurement. The more potent antagonists showed the slowest unblocking
      rates. Using this simple method, novel NMDA antagonists can be screened to
      ascertain potency, kinetics of block and relative toxicity, prior to animal
      testing.

PMID- 8997625
TI  - Pharmacological characterization of the human P2Y4 receptor.
AB  - The P2Y4 receptor is a new member of the P2Y family which functionally behaves as
      a pyrimidinergic receptor. The pharmacological properties of the human P2Y4
      receptor have been characterized following its stable expression in 1321N1
      astrocytoma cells. UTP induced a biphasic accumulation of inositol
      trisphosphates, with an early peak at 30 s followed by a smaller but more
      sustained accumulation. ATP was a pure antagonist at early times and later
      behaved as a partial agonist. At 20 min, the rank order of potency of various
      nucleotides was the following: UTP > UDP = deoxy UTP > 5-bromo-UTP > ITP > ATP.
      Diadenosine polyphosphates also stimulated the production of inositol
      trisphosphates (after 20 min), more potently than ATP, but their maximal effect
      represented only 20-25% of that of UTP. Pyridoxal-phosphate-6-azophenyl-2',4'
      disulphonic acid inhibited strongly the UTP response, whereas suramin was
      inactive and reactive blue 2 had an intermediate effect. Pertussis toxin
      inhibited the response to UTP at early times (62 +/- 5% inhibition at 30 s), but
      its effect was no longer observed at 5 or 20 min. It is speculated that the P2Y4
      receptor can exist in two distinct activation states differing in terms of time
      course, specificity for uridine nucleotides and G-protein coupling.

PMID- 8997626
TI  - Differences in isoproterenol stimulation of Ca2+ current of rat ventricular
      myocytes in neonatal compared to adult.
AB  - The developmental changes in the isoproterenol stimulation of the L-type calcium
      current (ICa(L)) were studied in freshly isolated neonatal (3-5-day-old) and
      adult (2-3-month-old) rat ventricular myocytes using whole-cell voltage clamp (at
      room temperature). ICa(L) was measured as the peak inward current at a test
      potential of +10 mV (or +20 mV) by applying a 300 ms pulse from a holding
      potential of -40 mV. The pipette solution was Cs(+)-rich and Ca(2+)-free. The
      external solution was Na(+)-free and K(+)-free. Isoproterenol stimulated ICa(L)
      in a dose-dependent manner. The concentrations of isoproterenol for half-maximal
      effect were 6.8 nM in neonatal and 13.3 nM in adult. The maximal stimulation of
      ICa(L) was 147 +/- 14% in neonatal and 97 +/- 7% in adult. The steady-state
      inactivation curves were not affected by isoproterenol, whereas the steady-state
      activation curve was shifted to the left in both neonatal and adult. Forskolin
      (10 microM) increased ICa(L) by 105 +/- 10% in neonatal and 90 +/- 12% in adult.
      After stimulating ICa(L) by forskolin, the addition of isoproterenol produced a
      further increase of ICa(L) by 99 +/- 27% in neonatal, but only by 19 +/- 3% in
      adult. The presence of an inhibitor of cAMP-dependent protein kinase in the
      pipette did not affect this marked difference between neonatal (87 +/- 23%) and
      adult (11 +/- 8%). We conclude that, in rat ventricular myocytes, (1) stimulation
      of ICa(L) by the beta-adrenoceptor agonist, isoproterenol, is already fully
      developed in the neonatal stage and actually decreases during development; (2)
      there is evidence for a cAMP-independent stimulation of Ca2+ channels by
      isoproterenol, and this is greater in neonatal than in adult. We believe that the
      cAMP-independent pathway is the direct pathway mediated by Gs alpha protein.

PMID- 8997627
TI  - Protective effect of l-cis-diltiazem on hypercontracture of rat myocytes induced
      by veratridine.
AB  - The protective effect of l-cis-diltiazem, the stereoisomer of d-cis-diltiazem,
      was studied against the veratridine-induced hypercontracture of rat myocytes.
      Veratridine increased both [Na+]i and [Ca2+]i, but did not cause hypercontracture
      in the absence of extracellular Ca2+. Both l-cis-diltiazem (0.1-10 microM) and d
      cis-diltiazem (10-30 microM) inhibited the hypercontracture and the increase in
      [Ca2+]i in a concentration-dependent manner. However, l-cis-diltiazem did not
      exert a negative inotropic effect in K+ (20 mM)-depolarized rat papillary muscles
      even at a dose of 10 microM. As seen in the case of tetrodotoxin, l-cis-diltiazem
      and d-cis-diltiazem also suppressed the increase in [Na+]i. The results show that
      l-cis-diltiazem prevents the veratridine-induced hypercontracture of myocytes by
      suppression of the [Ca2+]i increase. The attenuation of the [Ca2+]i increase by l
      cis-diltiazem was not dependent on inhibition of Ca2+ channels, but was partly
      due to inhibition of excessive Na+ entry via veratridine-modified Na+ channels.

PMID- 8997628
TI  - Vitamin C and E prevent lipopolysaccharide-induced apoptosis in human endothelial
      cells by modulation of Bcl-2 and Bax.
AB  - Lipopolysaccharide induced apoptosis and necrosis of human umbilical venous
      endothelial cells in a time-dependent manner. Lipopolysaccharide (1 microgram/ml)
      induced apoptosis was maximal after 18 h, whereas necrosis occurred after
      prolonged incubation for more than 24 h. The increase in apoptosis correlated
      with a reduction in Bcl-2, a potent cell death inhibitor. Furthermore,
      lipopolysaccharide treatment upregulated Bax, which heterodimerizes with and
      thereby inhibits Bcl-2. Both the antioxidant N-acetylcysteine and the combination
      of vitamin C and E (10 microM) completely inhibited lipopolysaccharide-induced
      apoptosis, whereas vitamin C or E alone was less effective. The reduction of
      lipopolysaccharide-induced apoptosis by vitamin C and E was paralleled by an
      increase in Bcl-2 and a decrease in Bax protein levels. Thus, vitamin C and E
      seem to interfere with the Bcl-2 family of apoptosis regulators in human
      umbilical venous endothelial cells.

PMID- 8997629
TI  - Enhancement of tamoxifen-induced E-cadherin function by Ca2+ channel antagonists
      in human breast cancer MCF7/6 cells.
AB  - Despite its intensive use in adjuvant breast cancer therapy for more than 30
      years, the exact mechanisms of action of tamoxifen have not yet been fully
      characterized. Tamoxifen was recently shown to restore the E-cadherin function of
      human breast cancer MCF7/6 cells and to suppress their invasive phenotype.
      Because tamoxifen interacts with targets implicated in Ca2+ homeostasis, we
      explored the possibility that the restoration of E-cadherin function in MCF7/6
      cells induced by this drug could be affected by Ca2+ modulators. Two different
      Ca2+ channel antagonists (verapamil and nifedipine) potentiated the effect of
      tamoxifen on E-cadherin function, as evaluated with a fast cell aggregation
      assay. These molecules decreased the tamoxifen concentration needed to restore
      the E-cadherin function from 10(-6) M to 10(-7) M. When incubated with a Ca2+
      channel agonist, Bay K8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2
      trifluoro-methylphenyl)- pyridine-5-carboxylate), the effect of tamoxifen on E
      cadherin function was completely abolished. These results demonstrate that the
      restoration of the E-cadherin function induced by tamoxifen depends, at least in
      part, on a Ca2+ pathway, and support the evidence of an effect of tamoxifen on
      Ca(2+)-dependent mechanisms. Our data also suggest that Ca2+ channel modulators
      could make it possible to decrease the dose of tamoxifen administered to patients
      without reducing the therapeutic effects.

PMID- 8997630
TI  - Iloperidone binding to human and rat dopamine and 5-HT receptors.
AB  - Iloperidone (HP 873; 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1
      piperidinyl]propoxy] -3- methoxyphenyl]ethanone) is a compound currently in
      clinical trials for the treatment of schizophrenia. Iloperidone displays affinity
      for dopamine D2 receptors and for 5-HT2A receptors and has a variety of in vivo
      activities suggestive of an atypical antipsychotic. Here we present an
      examination of the affinity of iloperidone to a variety of human and rat homologs
      of dopamine and 5-HT receptor subtypes. We employed receptor binding assays using
      membranes from cells stably expressing human dopamine D1, D2S, D2L, D3, D4 and D5
      and 5-HT2A and 5-HT2C receptors and rat 5-HT6 and 5-HT7 receptors. Iloperidone
      displayed higher affinity for the dopamine D3 receptor (Ki = 7.1 nM) than for the
      dopamine D4 receptor (Ki = 25 nM). Iloperidone displayed high affinity for the 5
      HT6 and 5-HT7 receptors (Ki = 42.7 and 21.6 nM, respectively), and was found to
      have higher affinity for the 5-HT2A (Ki = 5.6 nM) than for the 5-HT2C receptor
      (Ki = 42.8 nM). The potential implications of this receptor binding profile are
      discussed in comparison with data for other antipsychotic compounds.

PMID- 8997631
TI  - Ibogaine selectively inhibits nicotinic receptor-mediated catecholamine release.
AB  - The effects of ibogaine, a putative anti-addictive drug, on stimulated
      catecholamine release were examined in cultured chromaffin cells to clarify its
      mechanism(s) of action. Low concentrations of ibogaine (1-10 microM) had a
      selective inhibitory action on nicotinic receptor-mediated catecholamine release,
      while higher concentrations (100 microM) inhibited additional modes of stimulated
      catecholamine release. These results suggest a selective inhibitory action of
      ibogaine at the nicotinic acetylcholine receptor, possibly at the receptor ion
      channel site.

PMID- 8997633
TI  - Current status of the molecular genetic analysis of the rat major
      histocompatibility complex.

PMID- 8997632
TI  - Anxiogenic-like effect of the neuropeptide Y Y1 receptor antagonist BIBP3226:
      antagonism with diazepam.
AB  - The effect of the novel non-peptide neuropeptide Y Y1 receptor antagonist
      BIBP3226, N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)-methyl]-D-arginine amide, on
      exploratory behaviour of rats in the elevated plus-maze was studied. BIBP3226
      (0.5 and 5 micrograms, i.c.v.) induced an anxiogenic-like effect at the higher
      dose tested. This effect was antagonised by diazepam (0.5 mg/kg). The anxiogenic
      like effect of BIBP3226 was not related to a decrease in general locomotor
      activity. These findings support the hypothesis that neuropeptide Y Y1 receptor
      subtype is involved in anxiety regulation.

PMID- 8997634
TI  - Genetic linkage maps of the rat derived from an intercross and recombinant inbred
      strains originating from the BN.Lx and SHR progenitors.

PMID- 8997635
TI  - Recombinant inbred and congenic strains for mapping of genes that are responsible
      for spontaneous hypertension and other risk factors of cardiovascular disease.
AB  - The spontaneously hypertensive rat (SHR) is the most widely used animal model of
      human essential hypertension. In the SHR strain, as in humans, the high blood
      pressure is determined multifactorially. Analysis of genetically segregating
      populations, derived from SHR and normotensive inbred strains, enabled
      localization of quantitative trait loci (QTLs) responsible for blood pressure
      regulation on several rat chromosomes. Analysis of specialized strains, congenic
      and recombinant inbred (RI) strains, helped to analyze some of these mapping
      results in detail: (1) analysis of congenic strains provided definitive evidence
      for the presence of blood pressure regulatory genes on chromosomes 8 and 13 and
      will enable mapping of responsible genes to limited segments of differential
      chromosomes, (2) the RI strains were shown to be especially useful for genome
      scanning studies of complex traits and for correlation analysis of blood pressure
      and other risk factors of cardiovascular disease such as cardiac hypertrophy,
      dyslipidemia, and insulin resistance.

PMID- 8997636
TI  - Recombinant inbred and congenic strains of the rat for genetic analysis of limb
      morphogenesis.
AB  - Recombinant inbred (RI) and congenic strains carrying the polydactyly-luxate
      syndrome (PLS) provide an experimental model for the analysis of polygenic
      control of limb development. PLS is determined by a major gene Lx whose
      phenotypic expression is strongly influenced by the genetic background upon which
      it operates. The morphometric analysis of the skeleton of front and hind legs has
      been carried out. The morphotypes of PLS in RI strains exhibit a continuous
      variability and transgressive variation compared to BN.Lx and SHR.Lx morphotypes,
      which strongly indicates the polygenic effects on PLS manifestation. Quantitative
      trait loci (QTL) were searched for through correlation of genetic markers and
      morphometric traits. The association analysis revealed statistically significant
      correlations (P < 0.0003) of morphometric traits with two markers on chromosome 4
      (Il6 and A2m) associated with the number of front feet and hind feet phalanges,
      respectively, one marker on chromosome 7 (D7Mit17) associated with the tibia
      length, and the somatostatin gene on chromosome 11 associated with the number of
      front feet phalanges. In addition, suggestive associations of morphometric traits
      with markers on further nine chromosomes have been found (correlation
      coefficients ranging from 0.5 to 0.6). The verification of all these findings is
      in progress by means of double congenic strains which, in addition to the Lx
      gene, carry differential chromosome segments with putative modifiers.

PMID- 8997637
TI  - The teratogenic action of retinoic acid in rat congenic and recombinant inbred
      strains.
AB  - The teratogenic effect of all-trans retinoic acid (RA) was tested in the system
      of congenic and recombinant inbred (RI) strains of the laboratory rat carrying
      the mutant Lx allele which determines the polydactyly-luxate syndrome. It was
      demonstrated that the teratogenic effect of RA is influenced by both the genotype
      at the Lx locus and the modifying genes. The dose of 100 mg/kg administered by
      gavage on day 11 of pregnancy induced a statistically significant incidence of
      preaxial polydactyly in hind limbs of LEW/BN, +/Lx foetuses heterozygous in the
      mutant allele, whereas no specific limb defects were noted in foetuses LEW/BN,
      +/+ without the mutant allele. In foetuses homozygous in the mutant allele
      LEW/BN, Lx/Lx and SHR/BXH2, Lx/Lx, RA conversely induced a significant reduction
      in the number of toes on the preaxial side of hind limbs and a reduction of the
      zeugopodium, mostly the tibia. Reduction changes were more marked in SHR/BXH2,
      Lx/Lx foetuses, in which the tibia was entirely missing and sirenomelia was
      found. The foetuses in this group have in their genetic background a combination
      of modifiers that are responsible for oligodactyly and tibial hemimelia in the
      BXH2 strain. On the basis of continuing mapping of the rat genome, the testing of
      RA in the system of RI and congenic strains will be utilized for identification
      of so far hypothetical genes involved in morphogenesis.

PMID- 8997639
TI  - The cleavage of host cell proteins by HIV-1 protease.

PMID- 8997640
TI  - Interaction between quercetin and heat shock. A preliminary study on the chick
      embryo.
AB  - A hyperthermic shock (43 degrees C/30 min) enhances in somite stages of the chick
      embryo development the activity of the caudal morphogenetic system, manifested by
      intensive growth of the embryonic trunk. The exposure also induced the synthesis
      of heat shock proteins (HSP 70). A single administration of a bioflavonoid
      quercetin dissolved in DMSO to chick embryos in stages HH 10-11 (10-14 somites)
      prior to heat exposure inhibited both the growth acceleration and the HSP
      induction.

PMID- 8997638
TI  - The rat: an experimental animal in search of a genetic map.

PMID- 8997641
TI  - Bacterial immunomodulator Olimunostim inhibits degranulation of mastocytes in
      vitro.
AB  - A bacterial immunomodulator Olimunostim (OS) is one of the first Czech biologic
      response modifiers, which have been introduced into clinical practice. OS
      activates the mechanisms of non-specific immunity and is used for the most part
      in chronic infections. Since OS is indicated in patients suffering from infection
      complicated allergic diseases (asthma bronchiale, atopic eczema, etc.), (1) the
      concentration of histamine (Hi) and Hi-like compounds in OS, and (2) the possible
      role of OS in the process of histamine release from rat peritoneal mastocytes
      (PMC) were studied. The cells were preincubated with soluble fractions of OS. PMC
      degranulation was stimulated by the compound 48/80. The amount of Hi and Hi-like
      substances in the supernatant and in the pellet of PMC was determined by the
      fluorimetric method. Compounds of Hi nature were also evaluated in OS (lysate of
      S. aureus, K. pneumoniae, P. acnes) by original modification of high-performance
      liquid chromatography. The data provide the first evidence for a dose-dependent
      inhibitory effect of OS on the degranulation of rat PMC. Moreover, we found that
      1 mg of OS itself contained 0.376 microgram of Hi and 0.142 microgram of 1
      methylHi. Histamine was detected in P. acnes (0.672 microgram/mg), K. pneumoniae
      (0.136 microgram/mg), and S. aureus (0.175 microgram/mg), while methylHi was
      detected only in the case of K. pneumoniae (0.454 microgram/mg). The results of
      our in vitro study do not support the hypothesis of inducing type I allergic
      reaction by OS or facilitating OS in crossing the enteral barrier.

PMID- 8997642
TI  - HLA class II gene frequency in a Czech Population.
AB  - In a sample of 212 healthy, unrelated individuals of a Czech (Central Bohemian)
      population, the phenotype and allele frequencies of HLA-DRB1 and -DQB1 loci were
      determined. DNA typing technique used was the restriction fragment length
      polymorphism (RFLP) analysis. The restriction enzymes were TaqI and HindIII and
      specific DRB1 and DQB1 probes were applied. The most frequent DRB1 and DQB1
      alleles found were DRB1*11 and DQB1*06, their respective frequencies being 0.1698
      and 0.2594.

PMID- 8997645
TI  - Ultrastructure of the tracheal epithelium in rabbits after acetylcholine
      administration.
AB  - The ultrastructure of the tracheal epithelium was studied 5 and 20 min after
      intravenous (i.v.) administration of 0.5 mg of acetylcholine. As a result of this
      treatment, the goblet cells were overstimulated and damaged, and the mechanism of
      their secretion was accelerated. Only a mild pathological alteration was
      encountered in the ciliated cells. According to our classification, the degree of
      secretory element damage was severe, the injury to the ciliary border was
      moderate. The morphological signs of the severe impairment of the self-cleaning
      ability of the epithelium were inspissated mucus and very numerous bacteria in
      the area among free cilia.

PMID- 8997644
TI  - Essential fatty acid deficiency and bone fragility in rats.
AB  - This study demonstrates the effect of essential fatty acid deficiency on the
      postnatal skeletal development in the rat. Four groups (n = 10) of newborn Wistar
      rats were fed diets containing high and low proportions of essential fatty acids
      in the lipid fraction until day 16 after birth. Suckled littermates were used as
      controls. X-ray and histological studies showed the occurrence of multiple
      pathological fractures of the long bones in 1-month-old rats fed a diet deprived
      of essential fatty acids. No effect of high (51,000 IU/100 g diet) and low (5,100
      IU/100 g diet) concentrations of vitamin D2 was observed in our experiment. Thus,
      these data suggest the importance of essential fatty acids for bone pathology in
      the rat.

PMID- 8997643
TI  - Frequent detection of reviraemia in ducks persistently infected with avian
      leukosis retroviruses.
AB  - Ducks intraembryonally infected with avian leukosis viruses of subgroup C (ALV-C)
      were followed for a long period (up to 6.8 years), and the viraemia and
      production of virus-neutralizing antibodies were measured. In three independent
      experiments comprising ducks inoculated with uncloned and/or molecularly cloned
      ALV-C, we found that after the elimination of primary post-hatching viraemia,
      reviraemia could be detected in 60-70% of infected animals. Based on the course
      of viraemia, the individual ducks were assigned to four different groups: Group I
      (no reviraemia), Group II (one transient reviraemic period), Group III (one
      persistent reviraemic period), Group IV (fluctuating reviraemia). In comparison
      to sera from ducks included in Group I and/or II, a significant decrease in
      neutralizing activity of sera from animals comprised in Group III and/or IV was
      observed. Two out of four reviraemic viruses were not neutralized by antiserum
      against ALV-C, instead their infectivity was enhanced. Long-term follow-up of the
      cell-associated virus revealed that its rescuability by cocultivation with
      chicken embryo fibroblasts fluctuated in about 50% of animals. In the reviraemic
      phase of infection, integrated proviruses could be detected by Southern blotting
      in a majority of tissues examined. Our data document that many features
      recognized in lentiviruses are valid also for oncoviruses transmitted to
      heterologous hosts and substantiate further the suitability of ALV-C-infected
      ducks as a model for studying persistent retroviral infection.

PMID- 8997646
TI  - Radioprotective properties of flurbiprofen.
AB  - Repeated administration of flurbiprofen, an inhibitor of prostaglandin synthesis
      (IPS), was found to enhance haemopoiesis in mice exposed to a sublethal dose of
      fractionated gamma-irradiation (5 x 3 Gy, intervals between fractions 24 h). In
      lethally irradiated animals (5 x 3 Gy and an additional "top-up" dose of 3.5 Gy),
      a significantly better survival was found in mice given flurbiprofen than in
      control animals receiving saline. The latter result is a new positive phenomenon
      not observed in earlier experiments with other IPS. The findings suggest a
      possibility to extend the radiation dose range, in which the administration of
      IPS leads to radioprotective effects, also to higher, lethal radiation doses, by
      administering flurbiprofen instead of previously studied IPS indomethacin or
      diclofenac.

PMID- 8997647
TI  - Resorption rates of 2 commercially available bioresorbable membranes. A
      histomorphometric study in a rabbit model.
AB  - The respective resorption rates of recently commercialized collagen versus
      polylactic acid-citric acid ester membranes were compared. 16 rabbits were
      implanted with 2 mm x 4 mm pieces of membrane of both types in the alveolar
      mucosa just apically to the incisors on either side of the mouth. 1 animal was
      sacrificed on day 0, just after the operation. The others were sacrificed at 1,
      2, 3, 5, 7, 9 and 12 weeks. The specimens were prepared for histologic
      examination. Observations showed that the cross-linked collagen membranes induced
      severe inflammation and were resorbed within 2 weeks. The polylactic acid-citric
      acid ester polymer barriers produced a much more moderate infiltrate and were
      still not totally resorbed at 12 weeks. Although resorption rates in the rabbit
      may not be similar to those observed in humans, it seems that the durability of
      the polymer barrier is more adequate for guided tissue regeneration than the
      cross-linked collagen.

PMID- 8997648
TI  - The onset of diabetes and poor metabolic control increases gingival bleeding in
      children and adolescents with insulin-dependent diabetes mellitus.
AB  - Gingival health (bleeding on probing) and oral hygiene (plaque percent) were
      assessed in 2 groups of children and adolescents with insulin-dependent diabetes
      mellitus (IDDM). 1st study group included 12 newly diagnosed diabetic children
      and adolescents (age range 6.3-14.0 years, 5 boys and 7 girls). They were
      examined on the 3rd day after initial hospital admission and at 2 weeks and 6
      weeks after initiation of insulin treatment. Gingival bleeding decreased after 2
      weeks of insulin treatment (37.8% versus 19.0%, p < 0.001, paired t-test), and
      remained at the same level when examined 1 month later while glucose balance was
      excellent. Another group (n = 80) of insulin-dependent diabetic children and
      adolescents (age range 11.7-18.4 years, 44 boys and 36 girls) with a mean
      duration of diabetes 6.0 years (range 0.3-15.0 years) were examined 2x at 3-month
      intervals. Subjects with poor blood glucose control (glycosylated haemoglobin,
      HbA1, values over 13%) had more gingival bleeding (46.3% on examination 1, 41.7%
      on examination 2) than subjects with HbA1 values less than 10% (mean gingival
      bleeding 35.2% and 26.9%, respectively) or subjects with HbA1 values between 10
      to 13% (mean gingival bleeding 35.6% and 33.4%, respectively). Differences were
      significant on both examinations (p < 0.05, Anova), and remained significant
      after controlling the groups for differences in age, age at the onset of
      diabetes, duration of diabetes and pubertal stage (Ancova). Results were not
      related to differences or changes in dental plaque status, supporting the concept
      that imbalance of glucose metabolism associated with diabetes predisposes to
      gingival inflammation. An increase in gingival bleeding in association with
      hyperglycaemia suggests that hyperglycaemia-associated biological alterations,
      which lower host resistance toward plaque, have apparently taken place.
      Consequently, although not all gingivitis proceeds into a destructive periodontal
      disease, prevention of plaque-induced gingival inflammation should be emphasised,
      particularly in children and adolescents with poorly controlled diabetes.

PMID- 8997649
TI  - Saliva composition in children and young adults with Papillon-Lefevre syndrome.
AB  - The aim of the present study was to evaluate the salivary secretion rate and
      composition in a group of 16 children and young adults (6-27 years) with Papillon
      Lefevre Syndrome (PLS), and to compare the findings with a group (n = 16) of
      healthy controls. Unstimulated and stimulated whole saliva was collected at least
      2 h after meals and the secretion rate determined. The stimulated saliva was
      assessed for buffer capacity, total protein, peroxidase and hexosamine, while the
      unstimulated samples were evaluated for total protein, lysozyme, thiocyanate,
      lactoferrin and salivary IgA. Both the unstimulated (p < 0.01) and stimulated (p
      < 0.05) saliva secretion rates were significantly lower among the PLS patients
      compared with the controls. Furthermore salivary buffer capacity was
      significantly (p < 0.01) lower in the PLS patients. The total protein content in
      saliva was comparatively high in the study group, while the concentrations of
      immunoglobulins and non-immunoglobulins were within normal ranges. When
      calculating the output of the assessed antimicrobial factors, the mean peroxidase
      level in stimulated whole saliva was found to be significantly (p < 0.01) lower
      in the PLS patients than in the healthy controls. In conclusion, the present
      study indicates an impaired water secretion and a somewhat altered saliva gland
      function in children and young adults with PLS.

PMID- 8997651
TI  - The effect of hexetidine spray on dental plaque following periodontal surgery.
AB  - The aim of the present study was to determine the effects of a 0.2% hexetidine
      spray, used as a supplement to regular oral hygiene measures, on dental plaque
      and gingival condition following periodontal surgery. This study was carried out
      on 38 patients who required 2 episodes of periodontal surgery. Examinations
      regarding dental plaque were performed at 0, 7, 14, 21 and 28 days, while the
      condition of the gingiva were examined at 0 and 28 days. Dental plaque was
      assessed by the Turesky modification of Quigley-Hein index; the gingival
      condition was evaluated using the gingival index of Loe-Silness and the papilla
      bleeding index. In a double-blind cross-over study of 28 days duration,
      significant reduction in plaque accumulation and an improvement in wound healing
      were demonstrated for the test spray compared to the placebo.

PMID- 8997650
TI  - Periodontal healing following reconstructive surgery: effect of guided tissue
      regeneration.
AB  - Clinical healing following guided tissue regeneration (GTR) in deep intrabony
      pockets was compared to healing following gingival flap surgery alone (GFS). 15
      patients received the GTR treatment including an expanded polytetrafluoroethylene
      membrane. 13 other patients received the control treatment GFS. A postsurgery
      protocol emphasizing wound stability and infection control was used. Treatment
      effects were evaluated 6 months postsurgery. Mean pre-surgery probing depth for
      the GTR and control treatments was 7.5 +/- 1.0 and 7.7 +/- 1.5 mm, respectively.
      Significant probing depth reduction (3.8 +/- 1.2 and 2.9 +/- 1.1 mm), attachment
      level improvement (2.4 +/- 2.1 and 2.2 +/- 1.2 mm) and bone fill (2.0 +/- 2.0 and
      2.4 +/- 0.9 mm) followed the GTR and control protocols, respectively (p < 0.01).
      Significant differences between GTR and control treatments were observed in
      probing depth reduction (p < 0.01) and in gingival recession increase (1.7 +/-
      1.5 and 0.7 +/- 0.9 mm, respectively; p < 0.05). The results suggest that GTR
      procedures compared to GFS have similar clinical potential in intrabony pockets,
      under the present protocol.

PMID- 8997652
TI  - In vitro and in vivo studies on salifluor/PVM/MA copolymer/NaF combination as an
      antiplaque agent.
AB  - Salifluor (5-n-octanoyl-3'-trifluoromethyl-salicylanilide), a broad spectrum
      antimicrobial agent, was investigated for its ability to inhibit dental plaque
      formation. A combination of salifluor with PVM/MA copolymer and NaF was optimized
      for its antiplaque effect in mouthrinse and dentifrice formulations based on a
      series of both laboratory and clinical studies. It was found that salifluor, a
      highly hydrophobic compound, could not be adequately solubilized with the
      conventional amount of sodium lauryl sulfate (SLS), the most commonly used
      anionic surfactant in oral hygiene products. However, it was possible to prepare
      stable mouthrinse formulations using a mixed surfactant system containing both
      anionic and nonionic surfactants. The most suitable mixture was found to be a
      combination of SLS, Pluronic and Tauranol in a proportion of 1:1:1. This
      combination provided adequate stability and high antimicrobial activity as
      determined by in vitro microbiological tests. Addition of a PVM/MA copolymer to
      the formulation improved the adsorption and retention of salifluor on stimulated
      tooth surfaces in vitro (saliva coated hydroxyapatite disks) by almost two-fold
      and also increased the antiplaque efficacy in both laboratory and human clinical
      studies. It was also found that a non fluoride dentifrice containing a
      combination of salifluor and PVM/MA copolymer with a dicalcium phosphate
      dihydrate abrasive, was highly effective in reducing smooth surface and fissure
      caries in rats. The results of the present studies demonstrated that salifluor is
      an effective antiplaque agent in mouthrinse and dentifrice when carefully
      formulated to maximize its delivery and bioavailability on oral surfaces. They
      also illustrated the difficulties encountered in exploiting the antimicrobial
      efficacy of highly hydrophobic, nonionic antimicrobial agents such as salifluor
      in commonly used oral hygiene vehicles.

PMID- 8997654
TI  - The effect of toothpaste containing triclosan on oral mucosal desquamation. A
      model study.
AB  - SLS-containing toothpaste has previously been shown to cause oral mucosal
      desquamations when used in an experimental cap splint model. The aim of the
      present study was to examine the effect of toothpastes containing SLS in
      combination with triclosan on oral mucosal desquamation in a similar cap splint
      model system. It has previously been shown that the antibacterial agent triclosan
      also may have anti-inflammatory properties. The concentration of triclosan in the
      experimental toothpastes was 0.3%, while SLS varied from 1.5% to 3%. No oral
      mucosal desquamations were observed after use of a 1.5% SLS 0.3% triclosan
      containing toothpaste, contrary to the positive control toothpaste that contained
      1.5% SLS without triclosan. Furthermore, a statistically significant reduction in
      severe desquamations was observed after use of a toothpaste containing 3% SLS
      0.3% triclosan compared with the positive control. It may thus be suggested that
      triclosan exerts a moderating effect on desquamative reactions caused by SLS and
      that the effect is dependent on the relative amount of triclosan and SLS in the
      toothpastes.

PMID- 8997655
TI  - Generalized prepubertal periodontitis. A report of 4 cases with the immunological
      findings.
AB  - The clinical and immunological data from 4 patients with generalized prepubertal
      periodontitis are presented. The peripheral blood neutrophil chemotaxis was
      measured using zymosan activated sera as the chemoattractant. All of the 4
      patients have shown depressed neutrophil chemotaxis compared to those of the
      healthy controls. Peripheral blood lymphocyte subpopulations were analysed by
      double-coloured flow cytometry using monoclonal antibodies for the receptors CD2,
      CD3, CD4, CD8, CD19, CD29, CD45RA+, 34,29dK, CD56. CD11b/CD18. Lymphocytes
      bearing CD3 receptors showed a significant decrease compared to those of the
      controls. Natural killer cells were lowered in 3 of the 4 cases. All of the
      patients showed a higher increase in CD11b/CD18 expression. The evaluation of
      CD11b/CD18 receptor in peripheral blood leukocytes may be of help explaining the
      role of neutrophils in the pathogenesis of the disease.

PMID- 8997653
TI  - Prevalence of furcation involvements in patients referred for periodontal
      treatment.
AB  - The aim of this study was to evaluate the prevalence of furcation-involved molars
      in a patient sample referred for periodontal treatment. A total of 222 patients
      aged, 14-73 years (mean age 45 years), and with signs of destructive periodontal
      disease in at least 2 quadrants of the dentition were included in the study. The
      clinical examination involved assessments of oral hygiene status, gingival
      conditions, probing pocket depth and presence/degree of furcation involvement. In
      addition, a full mouth intraoral radiographic examination was performed. The
      results revealed that 4% of the patients presented with all 12 molars, while 3%
      had lost all molars. 52% of the individuals had at least 8 molars; 95% of
      subjects < 30 years of age and 19% in the age 60+ years. In patients aged > or =
      40 years, every 2nd molar showed advanced periodontal destruction in the
      furcation area. The prevalence of furcation involved molars was higher in the
      maxilla than in the mandible. From the age of 30 years, about 50% of the 1st and
      2nd molars in the maxilla showed at least 1 furcation site with deep involvement,
      while in the mandible a similar prevalence was observed first after the age of 40
      years. The highest frequency of furcation involvement was found at the distal
      site of the maxillary 1st molar (53%), and the mesial aspects of the maxillary
      2nd molar showed the lowest frequency (20%). Furcation sites with a probeable
      trunk region were observed at a frequency of 17-22% at the various tooth sites.
      It was concluded that tooth morphology may be an important factor that accounts
      for the variability in prevalence of molar furcation involvement.

PMID- 8997656
TI  - Comparative single-use plaque removal by toothbrushes of different designs.
AB  - Overall literature reviews have concluded that no one design of the manual
      toothbrush is superior for plaque removal. More recently, a toothbrush with
      filaments angled away from the head was shown to be more effective in several
      single-use studies than conventional designs. The aim of this study was to
      compare plaque removal by this new toothbrush and 3 other toothbrushes which had
      more conventional filament arrangements. 36 volunteers participated in this
      single-blind, randomised, 4-cell, crossover single use toothbrushing study. On
      day 1 of each period, volunteers brushed with a standard toothbrush and
      toothpaste for 60 s and then suspended oral hygiene for 48 h. On day 3,
      volunteers were scored for plaque by area and then brushed with the allocated
      test toothbrush with toothpaste for 60 s and plaque area was rescored. A washout
      of 4 days was allowed between test periods. The plaque areas were used to record
      the binary scores of the Rustogi et al. modification of the modified Navy plaque
      index but away from the clinic employing the Claydon and Addy procedural method
      for the index. Plaque removal scored by area and site were not significantly
      different between the brushes. This study is at variance with previous similar
      investigations which suggested that the new design of toothbrush head was
      superior for plaque removal. It is concluded again that there are no data which
      demonstrate unequivocally that any one manual toothbrush design is superior to
      any other for plaque removal.

PMID- 8997657
TI  - Extraoral apical elongation of deeply damaged roots with titanium posts. A
      comparison of 2 methods.
AB  - 42 very deeply fractured or otherwise damaged single roots which could not be
      saved by intra-alveolar transplantation only were replanted to a supragingival
      level after extraoral transapical elongation by either an ordinary titanium root
      screw (method 1) or a specially designed titanium post (TransApex, Dentatus)
      (method 2). After observation periods of x = 73 months (method 1) and x = 34
      months (method 2), 61% and 85% of the cases-respectively, were considered
      successful, fulfilling all 5 predefined success criteria. No other resorptions
      than slight surface resorptions were seen and all teeth showed very shallow
      pocket depths and physiological mobility, indicating that the long extraoral
      treatment had not caused lasting traumatic injury to the PDL cells. The most
      frequent complication in method 1 was periapical osteitis, indicating that the
      elongation system had become insufficient. On the other hand, the method showed
      the capacity to heal many of the pre-existing osteitis cases. Both root
      elongation techniques described in this report are comparatively inexpensive and
      safe, since the apical elongation is never extended beyond the lamina dura
      structure of the alveolus. Method 2 is to be preferred, however, as the specially
      designed through-and-through post-system which simultaneously provides apical
      closure, transapical elongation and coronal retention, allows treatment of even
      very short roots and seems to give better results.

PMID- 8997658
TI  - Matrix metalloproteinases and their inhibitors in gingival crevicular fluid and
      saliva of periodontitis patients.
AB  - Matrix metalloproteinases (MMPs) and serine proteinases seem to be related to
      tissue destruction in periodontitis. The presence of MMPs in gingival crevicular
      fluid (GCF) and saliva, however, has not been studied comprehensively with the
      enzyme-linked immunosorbent assay (ELISA)-technique. We therefore examined the
      levels of MMP-1, -3, -8 and -9, and their endogenous inhibitor, tissue inhibitor
      of matrix metalloproteinases (TIMP-1), in GCF and saliva of patients with adult
      periodontitis (AP) and localized juvenile periodontitis (LJP). Elevated levels of
      MMP-1 were detected in LJP GCF compared to AP and control GCF. Elevated levels of
      TIMP-1 were also detected in LJP GCF in comparison to AP and control GCF. Higher
      MMP-8 levels were detected in AP GCF compared to LJP and control GCF. The
      relative low levels of MMP-3 were present in all studied GCF samples. Elevated
      levels of MMP-8 were further detected in saliva of AP compared to LJP and the
      controls. Both MMP-1 and TIMP-1 were detected in all studied saliva samples, but
      not significant differences were detected between the studied groups. Our ELISA
      results confirm that (i) PMN MMP-8 and MMP-9 are the main collagenase and
      gelatinase in AP GCF, whereas GCF collagenase in LJP seems to be of the MMP-1
      type; (ii) only low levels of TIMP-1, endogenous MMP-inhibitor, are present in AP
      GCF, which emphasises the importance of doxycycline as a possible adjunctive drug
      in the treatment of AP patients; (iii) tests based on specific antibodies against
      PMN MMPs, especially MMP-8, might serve as a reliable method of measuring and
      monitoring enzyme levels in GCF from different periodontitis patients.

PMID- 8997659
TI  - Gingival fluid tetracycline release from bioerodible gels.
AB  - Intracrevicular antimicrobial therapy is consistent with the site-specific nature
      of periodontitis. Considerable research has focused on the use of nonresorbable
      fibers. However, a bioerodible system is desirable. The purpose of this study was
      to assess tetracycline release and safety following a single application of a
      syringable 35% tetracycline hydrochloride in a lactic-glycolic acid gel. 31
      generally healthy adult volunteers (mean age = 59 years) were enrolled in and
      completed this randomized, double-blind eight day study. 2, 6-10 mm non-adjacent
      interproximal pockets that bled on pocket probing were chosen as experimental
      sites in each subject. I experimental site and the surrounding gingival crevice
      received small particle size tetracycline in gel while the other site received
      larger particle size tetracycline in gel. Gingival crevicular fluid (GCF) was
      collected prior to treatment and 15 min, 1, 2, 3, 4 and 8 days post-treatment.
      GCF tetracyline concentrations were determined by agar diffusion bioassay and GCF
      volume measurements. 61% and 71% of sites had > or = 100 micrograms/ml
      tetracycline 3 days following application of large (mean concentration = 430 +/-
      92 micrograms/ml) and small particle gels (mean concentration = 418 +/- 70
      micrograms/ml), respectively. 37% and 55% of sites had measurable tetracycline 8
      days after placement of large (mean concentration = 86 +/- 31 micrograms/ml) and
      small particle gels (mean concentration = 293 +/- 79 micrograms/ml),
      respectively. The most common adverse event was "bitter taste" (10% of subjects).
      Based upon the reduction in probing depths and % of sites bleeding on probing at
      8 days relative to pretreatment, and the absence of any serious adverse events,
      it is concluded that these bioerodible gels are safe, and since the
      bacteriostatic range for most putative periodontopathogens is in the 2-10
      micrograms/ml range, the tetracycline levels observed at days 3 and 8 likely
      represent significant antimicrobial efficacy.

PMID- 8997660
TI  - The Journal of General Physiology.

PMID- 8997661
TI  - Mechanism of tetracaine block of cyclic nucleotide-gated channels.
AB  - Local anesthetics are a diverse group of ion channel blockers that can be used to
      probe conformational changes in the pore. We examined the effects of the local
      anesthetic tetracaine on rod and olfactory cyclic nucleotide-gated channels
      expressed from subunit 1 in Xenopus oocytes. We found that 40 microM tetracaine
      effectively blocked the bovine rod channel but not the rat olfactory channel at
      saturating concentrations of cGMP. By testing chimeric channels containing
      regions of sequence from both rod and olfactory channels, we found that
      determinants of apparent affinity for tetracaine at saturating cGMP did not map
      to any one region of the channel sequence. Rather, the differences in apparent
      affinity could be explained by differences between the chimeras in the free
      energy of the opening allosteric transition. If a channel construct (such as the
      rod channel) spent appreciable time in the closed state at saturating cGMP, then
      it had a high apparent affinity for tetracaine. If, on the other hand, a channel
      construct (such as the olfactory channel) spent little time in the closed state
      at saturating cGMP, then it had a low apparent affinity for tetracaine.
      Furthermore, tetracaine became more effective at low concentrations of cGMP and
      at saturating concentrations of cAMP, conditions which permit the channels to
      spend more time in the closed configuration. These results were well fit by a
      model in which tetracaine binds more tightly to the closed channel than to the
      open channel. Dose-response curves for tetracaine in the presence of saturating
      cGMP are well fit with a Michaelis-Menten binding scheme indicating that a single
      tetracaine molecule is sufficient to produce block. In addition, tetracaine block
      is voltage dependent with an effective z delta of +0.56. These data are
      consistent with a pore-block hypothesis. The finding that tetracaine is a state
      dependent pore blocker suggests that the inner mouth of the pore of cyclic
      nucleotide-gated channels undergoes a conformational change during channel
      opening.

PMID- 8997662
TI  - Identification of amino acid residues in the alpha, beta, and gamma subunits of
      the epithelial sodium channel (ENaC) involved in amiloride block and ion
      permeation.
AB  - The amiloride-sensitive epithelial Na channel (ENaC) is a heteromultimeric
      channel made of three alpha beta gamma subunits. The structures involved in the
      ion permeation pathway have only been partially identified, and the respective
      contributions of each subunit in the formation of the conduction pore has not yet
      been established. Using a site-directed mutagenesis approach, we have identified
      in a short segment preceding the second membrane-spanning domain (the pre-M2
      segment) amino acid residues involved in ion permeation and critical for channel
      block by amiloride. Cys substitutions of Gly residues in beta and gamma subunits
      at position beta G525 and gamma G537 increased the apparent inhibitory constant
      (Ki) for amiloride by > 1,000-fold and decreased channel unitary current without
      affecting ion selectivity. The corresponding mutation S583 to C in the alpha
      subunit increased amiloride Ki by 20-fold, without changing channel conducting
      properties. Coexpression of these mutated alpha beta gamma subunits resulted in a
      non-conducting channel expressed at the cell surface. Finally, these Cys
      substitutions increased channel affinity for block by external Zn2+ ions, in
      particular the alpha S583C mutant showing a Ki for Zn2+ of 29 microM. Mutations
      of residues alpha W582L, or beta G522D also increased amiloride Ki, the later
      mutation generating a Ca2+ blocking site located 15% within the membrane electric
      field. These experiments provide strong evidence that alpha beta gamma ENaCs are
      pore-forming subunits involved in ion permeation through the channel. The pre-M2
      segment of alpha beta gamma subunits may form a pore loop structure at the
      extracellular face of the channel, where amiloride binds within the channel
      lumen. We propose that amiloride interacts with Na+ ions at an external Na+
      binding site preventing ion permeation through the channel pore.

PMID- 8997663
TI  - Total charge movement per channel. The relation between gating charge
      displacement and the voltage sensitivity of activation.
AB  - One measure of the voltage dependence of ion channel conductance is the amount of
      gating charge that moves during activation and vice versa. The limiting slope
      method, introduced by Almers (Almers, W. 1978. Rev. Physiol. Biochem. Pharmacol.
      82:96-190), exploits the relationship of charge movement and voltage sensitivity,
      yielding a lower limit to the range of single channel gating charge displacement.
      In practice, the technique is plagued by low experimental resolution due to the
      requirement that the logarithmic voltage sensitivity of activation be measured at
      very low probabilities of opening. In addition, the linear sequential models to
      which the original theory was restricted needed to be expanded to accommodate the
      complexity of mechanisms available for the activation of channels. In this
      communication, we refine the theory by developing a relationship between the mean
      activation charge displacement (a measure of the voltage sensitivity of
      activation) and the gating charge displacement (the integral of gating current).
      We demonstrate that recording the equilibrium gating charge displacement as an
      adjunct to the limiting slope technique greatly improves accuracy under
      conditions where the plots of mean activation charge displacement and gross
      gating charge displacement versus voltage can be superimposed. We explore this
      relationship for a wide variety of channel models, which include those having a
      continuous density of states, nonsequential activation pathways, and
      subconductance states. We introduce new criteria for the appropriate use of the
      limiting slope procedure and provide a practical example of the theory applied to
      low resolution simulation data.

PMID- 8997664
TI  - Barium influx mediated by the cardiac sodium-calcium exchanger in transfected
      Chinese hamster ovary cells.
AB  - We examined Ba2+ influx using isotopic and fura-2 techniques in transfected
      Chinese hamster ovary cells expressing the bovine cardiac Na+/Ca2+ exchanger
      (CK1.4 cells). Ba2+ competitively inhibited exchange-mediated 45Ca2+ uptake with
      a Ki approximately 3 mM. Ba2+ uptake was stimulated by pretreating the cells with
      ouabain and by removing extracellular Na+, as expected for Na+/Ba2+ exchange
      activity. The maximal velocity of Ba2+ accumulation was estimated to be 50% of
      that for Ca2+. When the monovalent cation ionophore gramicidin was used to
      equilibrate internal and external concentrations of Na+, Ba2+ influx was
      negligible in the absence of Na+ and increased to a maximum at 20-40 mM Na+. At
      higher Na+ concentrations, Ba2+ influx declined, presumably due to the
      competition between Na+ and Ba2+ for transport sites on the exchanger. Unlike
      Ca2+, Ba2+ did not appear to be taken up by intracellular organelles. Thus,
      133Ba2+ uptake in ouabain-treated cells was not reduced by mitochondrial
      inhibitors such as-Cl-CCP or oligomycin-rotenone. Moreover, intracellular Ca2+
      stores that had been depleted of Ca2+ by pretreatment of the cells with ionomycin
      (a Ca2+ ionophore) remained empty during a subsequent period of Ba2+ influx. Ca2+
      uptake or release by intracellular organelles secondarily regulated exchange
      activity through alterations in [Ca2+]i. Exchange-mediated Ba2+ influx was
      inhibited when cytosolic [Ca2+] was reduced to 20 nM or less and was accelerated
      at cytosolic Ca2+ concentrations of 25-50 nM We conclude that (a) Ba2+
      substitutes for Ca2+ as a transport substrate for the exchanger, (b) cytosolic
      Ba2+ does not appear to be sequestered by intracellular organelles, and (c)
      exchange-mediated Ba2+ influx is accelerated by low concentrations of cytosolic
      Ca2+.

PMID- 8997665
TI  - Acceleration of sodium-calcium exchange activity during ATP-induced calcium
      release in transfected Chinese hamster ovary cells.
AB  - The P2U purinergic agonist ATP (0.3 mM) elicited an increase in [Ca2+]i due to
      Ca2+ release from intracellular stores in transfected Chinese hamster ovary cells
      that express the bovine cardiac Na+/Ca2+ exchanger (CK1.4 cells). The following
      observations indicate that ATP-evoked Ca2+ release was accompanied by a Ca(2+)
      dependent regulatory activation of Na+/Ca2+ exchange activity: Addition of
      extracellular Ca2+ (0.7 mM) 0-1 min after ATP evoked a dramatic rise in [Ca2+]i
      in Na(+)-free media (Li+ substitution) compared to Na(+)-containing media; no
      differences between Na(+)- and Li(+)-based media were observed with vector
      transfected cells. In the presence of physiological concentrations of
      extracellular Na+ and Ca2+, the ATP-evoked rise in [Ca2+]i declined more rapidly
      in CK1.4 cells compared to control cells, but then attained a long-lived plateau
      of elevated [Ca2+]i which eventually came to exceed the declining [Ca2+]i values
      in control cells. ATP elicited a transient acceleration of exchange-mediated Ba2+
      influx, consistent with regulatory activation of the Na+/Ca2+ exchanger. The
      acceleration of Ba2+ influx was not observed in vector-transfected control cells,
      or in CK1.4 cells in the absence of intracellular Na+ or when the Ca2+ content of
      the intracellular stores had been reduced by prior treatment with ionomycin. The
      protein kinase C activator phorbol 12-myristate 13-acetate attenuated the
      exchange-mediated rise in [Ca2+]i under Na(+)-free conditions, but did not
      inhibit the ATP-evoked stimulation of Ba2+ influx. The effects of PMA are
      therefore not due to inhibition of exchange activity, but probably reflect the
      influence of protein kinase C on other Ca2+ homeostatic mechanisms. We conclude
      that exchange activity is accelerated during ATP-evoked Ca2+ release from
      intracellular stores through regulatory activation by increased [Ca2+]i. In the
      absence of extracellular Ca2+, the stimulation of exchange activity is short
      lived and follows the time course of the [Ca2+]i transient; in the presence of
      extracellular Ca2+, we suggest that the exchanger remains activated for a longer
      period of time, thereby stabilizing and prolonging the plateau phase of store
      dependent Ca2+ entry.

PMID- 8997666
TI  - Cell swelling activates the K+ conductance and inhibits the Cl- conductance of
      the basolateral membrane of cells from a leaky epithelium.
AB  - Necturus gallbladder epithelial cells bathed in 10 mM HCO3/1% CO2 display sizable
      basolateral membrane conductances for Cl- (GClb) and K+ (GKb). Lowering the
      osmolality of the apical bathing solution hyperpolarized both apical and
      basolateral membranes and increased the K+/Cl- selectivity of the basolateral
      membrane. Hyperosmotic solutions had the opposite effects. Intracellular free
      calcium concentration ([Ca2+]i) increased transiently during hyposmotic swelling
      (peak at approximately 30 s, return to baseline within approximately 90 s), but
      chelation of cell Ca2+ did not prevent the membrane hyperpolarization elicited by
      the hyposmotic solution. Cable analysis experiments showed that the electrical
      resistance of the basolateral membrane decreased during hyposmotic swelling and
      increased during hyperosmotic shrinkage, whereas the apical membrane resistance
      was unchanged in hyposmotic solution and decreased in hyperosmotic solution. We
      assessed changes in cell volume in the epithelium by measuring changes in the
      intracellular concentration of an impermeant cation (tetramethylammonium), and in
      isolated polarized cells measuring changes in intracellular calcein fluorescence,
      and observed that these epithelial cells do not undergo measurable volume
      regulation over 10-12 min after osmotic swelling. Depolarization of the
      basolateral membrane voltage (Vcs) produced a significant increase in the change
      in Vcs elicited by lowering basolateral solution [Cl-], whereas hyperpolarization
      of Vcs had the opposite effect. These results suggest that: (a) Hyposmotic
      swelling increases GKb and decreases GClb. These two effects appear to be linked,
      i.e., the increase in GKb produces membrane hyperpolarization, which in turn
      reduces GClb. (b) Hyperosmotic shrinkage has the opposite effects on GKb and
      GClb. (c) Cell swelling causes a transient increase in [Ca2+]i, but this response
      may not be necessary for the increase in GKb during cell swelling.

PMID- 8997667
TI  - Proton pump activity of mitochondria-rich cells. The interpretation of external
      proton-concentration gradients.
AB  - We have hypothesized that a major role of the apical H(+)-pump in mitochondria
      rich (MR) cells of amphibian skin is to energize active uptake of Cl- via an
      apical Cl-/HCO3(-)-exchanger. The activity of the H+ pump was studied by
      monitoring mucosal [H+]-profiles with a pH-sensitive microelectrode. With
      gluconate as mucosal anion, pH adjacent to the cornified cell layer was 0.98 +/-
      0.07 (mean +/- SEM) pH-units below that of the lightly buffered bulk solution (pH
      = 7.40). The average distance at which the pH-gradient is dissipated was 382 +/-
      18 microns, corresponding to an estimated "unstirred layer" thickness of 329 +/-
      29 microns. Mucosal acidification was dependent on serosal pCO2, and abolished
      after depression of cellular energy metabolism, confirming that mucosal
      acidification results from active transport of H+. The [H+] was practically
      similar adjacent to all cells and independent of whether the microelectrode tip
      was positioned near an MR-cell or a principal cell. To evaluate [H+]-profiles
      created by a multitude of MR-cells, a mathematical model is proposed which
      assumes that the H+ distribution is governed by steady diffusion from a number of
      point sources defining a set of particular solutions to Laplace's equation. Model
      calculations predicted that with a physiological density of MR cells, the [H+]
      profile would be governed by so many sources that their individual contributions
      could not be experimentally resolved. The flux equation was integrated to provide
      a general mathematical expression for an external standing [H+]-gradient in the
      unstirred layer. This case was treated as free diffusion of protons and proton
      loaded buffer molecules carrying away the protons extruded by the pump into the
      unstirred layer; the expression derived was used for estimating stationary proton
      fluxes. The external [H+]-gradient depended on the mucosal anion such as to
      indicate that base (HCO3-) is excreted in exchange not only for Cl-, but also for
      Br- and I-, indicating that the active fluxes of these anions can be attributed
      to mitochondria-rich cells.

PMID- 8997668
TI  - Subunit stoichiometry of human muscle chloride channels.
AB  - Voltage-gated Cl- channels belonging to the ClC family appear to function as
      homomultimers, but the number of subunits needed to form a functional channel is
      controversial. To determine subunit stoichiometry, we constructed dimeric human
      skeletal muscle Cl- channels in which one subunit was tagged by a mutation
      (D136G) that causes profound changes in voltage-dependent gating. Sucrose-density
      gradient centrifugation experiments indicate that both monomeric and dimeric hClC
      1 channels in their native configurations exhibit similar sedimentation
      properties consistent with a multimeric complex having a molecular mass of a
      dimer. Expression of the heterodimeric channel in a mammalian cell line results
      in a homogenous population of Cl- channels exhibiting novel gating properties
      that are best explained by the formation of heteromultimeric channels with an
      even number of subunits. Heteromultimeric channels were not evident in cells
      cotransfected with homodimeric WT-WT and D136G-D136G constructs excluding the
      possibility that functional hClC-1 channels are assembled from more than two
      subunits. These results demonstrate that the functional hClC-1 unit consists of
      two subunits.

PMID- 8997669
TI  - Temperature dependence of fast and slow gating relaxations of ClC-0 chloride
      channels.
AB  - The chloride channel from the Torpedo electric organ, ClC-0, is the best studied
      member of a large gene-family (Jentsch, T.J. 1996. Curr. Opin. Neurobiol. 6:303
      310.). We investigate the temperature dependence of both the voltage- and
      chloride-dependent fast gate and of the slow gate of the "double-barreled" ClC-0
      expressed in Xenopus oocytes. Kinetics of the fast gate exhibit only a moderate
      temperature dependence with a Q10 of 2.2. Steady-state P(open) of the fast gate
      is relatively independent of temperature. The slow gate, in contrast, is highly
      temperature sensitive. Deactivation kinetics at positive voltages are associated
      with a Q10 of approximately 40. Steady-state open probability of the slow gate
      (P(open)slow(V)) can be described by a Boltzmann distribution with an apparent
      gating valence of approximately 2 and a variable "offset" at positive voltages.
      We note a positive correlation of this offset (i.e., the fraction of channels
      that are not closed by the slow gate) with the amount of expression. This offset
      is also highly temperature sensitive, being drastically decreased at high
      temperatures. Paradoxically, the maximum degree of activation of the slow gate
      also decreases at higher temperatures. The strong temperature dependence of the
      slow gate was also observed at the single channel level in inside-out patches.
      The results imply that within a Markovian-type description at least two open and
      two closed states are needed to describe slow gating. The strong temperature
      dependence of the slow gate explains the phenotype of several ClC-0 point-mutants
      described recently by Ludewig et al. (Ludewig, U., T.J. Jentsch, and M. Pusch.
      1996. J. Physiol. (Lond.). In press). The large Q10 of slow gating kinetics
      points to a complex rearrangement. This, together with the correlation of the
      fraction of noninactivating channels with the amount of expression and the fact
      that the slow gate closes both protochannels simultaneously suggests that the
      slow gate is coupled to subunit interaction of the multimeric ClC-0 channel.

PMID- 8997670
TI  - Full- versus partial-mouth disinfection in the treatment of periodontal
      infections. Long-term clinical observations of a pilot study.
AB  - A classical treatment for chronic adult periodontitis consists of four to six
      consecutive sessions of scaling and root planing at a 1- to 2-week interval. Such
      a so-called "quadrant or sextant therapy" might result in a reinfection of a
      previously disinfected area by bacteria from an untreated region. The purpose of
      this study was to investigate, over an 8-month period, the clinical benefits of
      full-mouth disinfection within a 24-hour period in the control of chronic
      periodontitis. Ten adult patients with advanced chronic periodontitis were
      randomly assigned to a test and a control group. The control group received the
      standard scheme of initial periodontal therapy, consisting of scaling and root
      planing of the four quadrants was performed within 24 hours and immediately
      followed by a thorough supra- and subgingival chlorhexidine application to limit
      any transfer of bacteria. The latter involved tongue brushing with a 1%
      chlorhexidine gel for 60 seconds, mouthrinsing with a 0.2% chlorhexidine solution
      twice for 60 seconds, repeated subgingival irrigation of all pockets with a 1%
      chlorhexidine gel (3 times within 10 minutes), and mouthrinsing twice daily with
      a 0.2% chlorhexidine solution during 2 weeks. In addition, both groups received
      thorough oral hygiene instructions. The plaque index, gingival index, probing
      depth, gingival recession, and bleeding on probing were recorded prior to
      professional cleaning and at 1, 2, 4, and 8 months afterwards. Although the test
      group scored higher plaque indices than the control group, especially at months 2
      and 4, the gingival index and bleeding tendency showed similar improvements with
      time. However, when the gingival/plaque ratio was considered, the latter was
      lower in the test group at all follow-up visits. For pockets > or = 7 mm, full
      mouth disinfection showed a significantly (P = 0.01) higher reduction in probing
      depth at each follow-up visit with, at month 8, a reduction of 4 mm (from 8 mm to
      4 mm), in comparison to 3 mm (from 8 mm to 5 mm) for the classical therapy. The
      increase in gingival recession in the full-mouth disinfection group remained
      below 0.7 mm, while in the control group it reached 1.9 mm after 8 months. This
      resulted in a gain of clinical attachment level of 3.7 mm for the test group
      versus 1.9 mm for the control group. A radiographical examination also indicated
      a superior improvement for the test group when compared to the control group.
      This pilot study suggests that a full-mouth disinfection in one day results in an
      improved clinical outcome in chronic periodontitis as compared to scalings per
      quadrant at 2-week intervals over several weeks.

PMID- 8997671
TI  - Metal substrates influence the release of glycosaminoglycan and transforming
      growth factor beta by human bone cells.
AB  - Bone cells derived from human jaw were isolated from explants and grown in vitro.
      Subcultures were cultured on plastic (control) and metal substrates for 24 and 48
      hours in medium containing 3H-glucosamine and labeled glycosaminoglycan (GAG)
      accumulation was measured. In bone cells cultured on metal substrates there was
      an evident reduction in the synthesis and secretion of radiolabeled
      macromolecules compared to bone cells cultured on plastic. Moreover, the
      accumulation of single GAG classes was specific for each substrate tested. The
      results showed that titanium was the only metal substrate studied in which the
      percentage of individual GAG classes remained the same as control cultures. GAG
      reduction was due to a decreased synthesis and not to an increased degradation as
      shown by the decrement of exoglycosidase activity. The metals also reduced the
      activity of transforming growth factor beta (TGF beta), measured using
      interleukin-1 assay method, a factor involved in the various phases of bone
      remodeling; in this case, too, cells grown on titanium showed the highest TGF
      beta activity compared to the other metal substrates studied. The results
      indicate that the substrate to which the cells adhere do exhibit specific
      differences in GAG composition and TGF beta activity. The differences observed
      may be important during in vivo events such as guided tissue regeneration and
      bone deposition.

PMID- 8997672
TI  - Increased expression of interleukin-1 receptors on fibroblasts derived from
      inflamed gingiva.
AB  - We investigated the expression of interleukin-1 receptors (IL-1R) on the surfaces
      of cultured gingival fibroblasts derived from healthy and inflamed gingiva and
      the effects of IL-1 alpha and IL-1 beta and prostaglandin E2 (PGE2) on IL-1R
      expression. Fibroblasts were obtained from explant culture of both healthy and
      inflamed gingiva. IL-1R on cell surfaces was detected immunohistochemically using
      an anti-human IL-1R monoclonal antibody. IL-1R expression was assessed
      quantitatively using an enzyme linked immunosorbent assay (ELISA). Positive
      staining for IL-1R was more evident on cells from inflamed gingiva compared with
      cells from healthy gingiva. The ELISA showed a significantly increased number of
      IL-1R on cells from inflamed gingiva compared with cells from healthy gingiva (P
      < 0.05). Treatment with IL-1 but not PGE2 increased expression of IL-1R on
      fibroblasts. These findings suggest that gingival fibroblast responses to IL-1
      may represent a mechanism for amplification of gingival inflammation.

PMID- 8997673
TI  - The effect of lipopolysaccharide on growth factor-induced mitogenesis in human
      gingival fibroblasts.
AB  - Quiescent and non-quiescent human gingival fibroblasts (HGF) were incubated for
      24 hours with Actinobacillus actinomycetemcomitans lipopolysaccharide (LPS)
      and/or growth factors (interleukin-1 beta [IL-1 beta], insulin, epidermal growth
      factor [EGF], platelet-derived growth factor [PDGF], fibroblast growth factor
      [FGF], and transforming growth factor-beta [TGF-beta]) to examine the ability of
      LPS to modify HGF proliferation in response to these autocrine and paracrine
      growth factors. A. actinomycetemcomitans LPS at high concentrations (> or = 9
      micrograms/well) generally resulted in a reduction in DNA synthesis in quiescent
      and non-quiescent fibroblasts; however, LPS at low concentrations (< 9
      micrograms/well) showed a minimal enhancement of DNA synthesis (40 to 60%) in
      quiescent and non-quiescent cells. HGF co-incubated with mitogenic agents and LPS
      (9 micrograms/well) exhibited suppression of growth factor-induced 3H-Tdr uptake
      compared to growth factor-stimulated controls. In contrast, 3H-Tdr uptake was
      slightly elevated with addition of LPS at low concentrations (0.09
      microgram/well). These trends were seen with all growth factors tested. Non
      quiescent cells, in general, were more responsive to the growth factors and
      LPS/growth factor combinations when compared to the quiescent HGF. HGF were
      further tested for the ability of LPS to alter growth factor responsiveness by
      pretreating the cells with LPS prior to incubation of the growth factor, as well
      as, subsequent addition of LPS to growth factor-pretreated cells. Similar
      patterns were observed as above, except IL-1 beta-pretreated quiescent and non
      quiescent HGF followed by LPS addition demonstrated a marked elevation in
      proliferation when compared to IL-1 beta stimulated controls. These findings
      suggest that LPS may potentially modulate the proliferative rate of connective
      tissue undergoing inflammatory or growth factor-induced reparative processes in
      periodontal lesions.

PMID- 8997674
TI  - Root surface removal with diamond-coated ultrasonic instruments: an in vitro and
      SEM study.
AB  - Adequate root preparation in periodontal procedures includes the removal of
      plaque, calculus, and perhaps contaminated cementum and dentin. The purpose of
      this study was to evaluate and compare the amount of root surface removal and
      residual surface texture using similarly shaped regular (US) and both fine
      (FINDIAM) and medium (MEDDIAM) grit diamond-coated ultrasonic inserts. Forty-five
      (45) premolars extracted for orthodontic reasons were randomly divided into 3
      groups of 15 teeth each. They were individually mounted in a jig and instrumented
      with a standardized 500 gram force while they were moved a precise horizontal
      distance of 12 mm over a 1.2 second period using specially designed and computer
      controlled instrumentation. Three measurements were made to the nearest 0.0005"
      at 3 points along the test area before instrumentation and after 10 and 20
      strokes. The mean depth of root structure removed was US 5.8 +/- 6.6 microns,
      FINDIAM 50.1 +/- 14.2 microns, MEDDIAM 30.8 +/- 12.1 microns, after 10 strokes,
      and US 12.7 +/- 10.9 microns, FINDIAM 83.3 +/- 20.1 microns, MEDDIAM 58.7 +/-
      17.9 microns after 20 strokes, respectively. All 3 instruments were different
      from each other (P < 0.001) in the 10 stroke group, while in the 20 stroke group
      FINDIAM and MEDDIAM were different from US (P < 0.001), but not from each other.
      Only FINDIAM showed a significant difference between 10 and 20 stroke values for
      depth of root removal. Modified loss of tooth substance index SEM scores
      indicated increasingly greater root surface roughness from US to FINDIAM to
      MEDDIAM. Substantially greater root surface removal and greater residual root
      surface roughness occurred with diamond-coated ultrasonic inserts under
      standardized in vitro conditions. These results suggest that caution should be
      used with diamond-coated ultrasonic instruments during periodontal root planing
      procedures.

PMID- 8997675
TI  - Image homogeneity and recording reproducibility with 2 techniques for serial
      intra-oral radiography.
AB  - The present study compared recording reproducibility and image homogeneity after
      applying two techniques for recording of serial intra-oral radiographs: 1) a
      technique previously described in 1990 based on mechanical fixation between the
      patient, the film holder, and the x-ray tube; and 2) a newly developed technique
      which operates with an optical alignment provided by a light beam. Twenty adults
      participated in the study. Two intra-oral radiographs were taken with a 30-minute
      time interval of the mandibular premolar/molar and the incisor region in each
      individual with either of the methods. All radiographs were scanned and
      digitized. Subtractions were performed between the two radiographs taken of the
      same individual and region with the same method. The standard deviation (SD) of
      the histogram defining the distribution of the grey shades in the subtraction
      image was used as the statistical test parameter. Subtractions were performed
      with an automated method and using a reference point-based program in order to
      test recording reproducibility and image homogeneity, respectively. Paired t
      tests revealed that the average SDs obtained by the mechanical fixation method
      and the optical method were not statistically significantly different neither
      when applying the automated nor the reference point-based subtraction method (P >
      0.05). The SDs increased significantly when the automated method was used
      compared to the reference point-based method (P = 0.001). In conclusion, the
      optical method and the mechanical method provided images of similar recording
      reproducibility and homogeneity.

PMID- 8997676
TI  - Reproducibility of attachment level recordings using an electronic and a
      conventional probe.
AB  - This study describes the variations in the reproducibility of attachment level
      recordings for different subjects at different examinations. Twenty patients with
      different degrees of periodontal disease were recruited and examined bi-monthly
      for their attachment levels using an electronic probe in two quadrants and a
      conventional probe in the other two quadrants. At each of the 7 examinations
      attachment level recordings were repeated with the appropriate probe after
      approximately 30 minutes. Results demonstrate that the reproducibility of
      attachment level recordings was slightly better for the conventional probe than
      for the electronic probe. Attachment level recording reproducibility varied
      considerably between subjects and between examinations for the same subject.
      Aggregation of attachment level recordings in the form of mean tooth values or
      mean individual values reduced the range of the differences, but considerable
      between-subject and between-examination variation was still seen. These results
      indicate that no single uniformly valid estimate of attachment level
      reproducibility exists which can be used to set diagnostic thresholds such that a
      minimum number of incorrect diagnoses are made.

PMID- 8997677
TI  - Periodontal repair in intrabony defects treated with a calcium carbonate implant
      and guided tissue regeneration.
AB  - Clinical outcome following the concurrent use of a porous resorbable calcium
      carbonate (CC) implant and guided tissue regeneration (GTR) in intrabony
      periodontal defects was evaluated in a randomized four-treatment parallel arm
      study. Eighty (80) patients, each contributing one interproximal intrabony
      defect, were assigned to the four treatments (20 patients per treatment)
      including the CC implant and GTR (CC + GTR), GTR alone (GTR control), CC implant
      alone (CC control), and gingival flap surgery alone (GFS control). Fourteen
      patients treated with CC + GTR, 19 patients treated with the GTR control, 13
      patients treated with the CC control, and 18 patients treated with the GFS
      control completed the study. Clinical healing was evaluated 6 months postsurgery
      and included changes in probing depth, clinical attachment level, probing bone
      level, and gingival recession. Postsurgery probing depth reduction was 4.5 +/-
      1.7 mm (CC + GTR; P < 0.01), 4.8 +/- 1.8 mm (GTR; P < 0.01), 3.7 +/- 2.2 mm (CC;
      P < 0.01), and 3.3 +/- 1.6 mm (GFS; P < 0.01). Clinical attachment gain amounted
      to 3.3 +/- 1.4 mm (CC + GTR; P < 0.01), 4.0 +/- 2.1 mm (GTR; P < 0.01), 3.0 +/-
      2.4 mm (CC; P < 0.01), and 2.0 +/- 1.7 mm (GFS; P < 0.01). The CC + GTR and GTR
      treatments exhibited significantly greater improvements compared to GFS (P <
      0.05). Postsurgery probing bone level gain amounted to 4.0 +/- 1.7 mm (CC + GTR;
      P < 0.01), 4.1 +/- 1.5 mm (GTR; P < 0.01), 4.0 +/- 2.2 mm (CC; P < 0.01), and 0.5
      +/- 2.0 mm (GFS; P > 0.05). The CC + GTR, GTR, and CC treatments exhibited
      significantly greater improvements compared to GFS (P < 0.05). Gingival recession
      increased significantly compared to presurgery for GTR, CC, and GFS treatments (
      0.9 +/- 1.2, -0.7 +/- 0.7, and -1.2 +/- 1.4 mm, respectively; P < 0.01). The
      results suggest that the concurrent use of a porous resorbable CC implant and GTR
      has limited adjunctive effect in the treatment of intrabony periodontal defects.

PMID- 8997679
TI  - Analytical methodology in quantitative digital subtraction radiography: analyses
      of the aluminum reference wedge.
AB  - An aluminum wedge can be used to quantify volumetric change in crestal alveolar
      bone which has been identified through subtraction radiography. This study
      compares two methods for using an aluminum wedge for this purpose: 1) the
      aluminum wedge is present in both radiographs and used to determine the aluminum
      equivalent bone density present in the region of change for each radiograph; and
      2) the aluminum wedge is present in only one radiograph and the difference image
      of the wedge in the subtraction image is used to calculate the aluminum
      equivalent change in bone density. Pairs of standardized x-rays were taken with
      synthetic bone chips of known weights placed when the second x-ray was taken. The
      volumetric change produced by the bone chips was calculated by the two methods.
      The relationship of the calculated volumes to the chip weights had a higher r2
      value (P < 0.05) for the two-wedge method than for the one-wedge method. The two
      wedge method is recommended for volumetric quantification of alveolar bone
      change. The influence of the clarity of the aluminum wedge image in the x-ray
      pairs was also examined in this study and found to be significant. Attention must
      be given to factors which affect the aluminum wedge image characteristics to
      achieve optimal results.

PMID- 8997678
TI  - Effect of a non-steroidal anti-inflammatory drug on tissue levels of
      immunoreactive prostaglandin E2, immunoreactive leukotriene, and pain after
      periodontal surgery.
AB  - The aim of this study was to measure tissue levels of immunoreactive
      prostaglandin E2 (iPGE2), immunoreactive leukotriene B4 (iLTB4), and pain after
      periodontal surgery and to evaluate the effect of the non-steroidal anti
      inflammatory drug (NSAID), ibuprofen, on these levels. Two contralateral
      quadrants in each of nine patients were selected to undergo separate surgical
      procedures, one with ibuprofen (800 mg 1 hour presurgery and 400 mg postsurgery)
      and one with a placebo. Intra-operatively, a custom-made microdialysis probe,
      with a 3,000 dalton molecular weight cut-off, was inserted beneath the soft
      tissue flap and a dialysate collected every 20 minutes for 4 hours after surgery.
      Pain perception was measured at the same time intervals using two pain scales.
      Dialysate samples were assayed using two enzyme immunoassays. Mean tissue levels
      of iPGE2 in the placebo group increased from 74 nM at 40 minutes to a peak of 261
      nM at 200 minutes. Mean tissue levels of iLTB4 in the placebo group fluctuated
      between 0.2 and 0.6 nM. Pain levels in this group increased continuously with
      time, peaking at 4 hours. Mean tissue levels of iPGE2 in the ibuprofen group were
      significantly suppressed, exhibiting more than a 95% reduction. This was
      accompanied by a significant reduction in pain. Ibuprofen had no detectable
      effect on tissue levels of iLTB4. These data indicate that iPGE2 and iLTB4 are
      present at relatively high concentrations in the periodontal tissues after
      surgery. Since these concentrations exceed the Kd values for binding to their
      respective receptors, PGE2 and LTB4 may be associated with the development of
      postsurgical pain and inflammation. These data also indicate that ibuprofen can
      successfully inhibit iPGE2 production in the periodontal tissues and in this way
      may help reduce postoperative pain and inflammation.

PMID- 8997680
TI  - Analysis of consecutively placed loaded root-form and plate-form implants in
      adult Macaca mulatta monkeys.
AB  - The present paper describes 36 consecutively treated non-human primates (Macaca
      mulatta) as part of a balanced block design study to examine osseointegration in
      root- and plate-form implants prepared by atraumatic preparation of bone.
      Clinical measurements around selected teeth and digital radiology were utilized
      to monitor periodontal disease and bone loss around root- and plate-form implants
      which were loaded with a fixed prosthesis. Results indicate that once monthly
      regimen of scaling and root planing can prevent attachment loss in natural teeth,
      serving as abutments of loaded bridges. Root-form implants exhibited a
      significant loss of crestal bone height during the first year (P < 0.03) while
      plate-form implants showed less loss in bone height. There was an increase in
      bone mass over time for root-form or plate-form implants. Both root-form and
      plate-form implants provided radiographic evidence of osseointegration in loaded
      bridges.

PMID- 8997681
TI  - Microbiota associated with consecutively placed loaded root-form and plate-form
      implants in adult Macaca mulatta monkeys.
AB  - This study describes the microbiota associated with consecutively placed root
      form and plate-form implants placed in similar mandibular arches of rhesus
      (Macaca mulatta) monkeys and loaded with similar prostheses. The teeth and
      implants were maintained by monthly scaling and root planing. Twenty-four round
      (root-form) and 24 flat (plate-form) implants were placed in the loci of #18 and
      #31 in 36 adult monkeys. The microbiota around implants and mandibular molar
      teeth were studied quarterly from the day prostheses were loaded (Day 0) for 12
      months. The microbiota were characterized by culture and dark field microscopy.
      Overall, levels of putative peri-implant pathogens studied declined or remained
      statistically unchanged at implant or mandibular molar sites. Levels of
      spirochetes and Porphyromonas species declined at mandibular molar teeth but
      increased at dental implant sites. Levels of A. actinomycetemcomitans declined
      significantly at implants and mandibular tooth sites during the period. No
      statistically significant difference was detected between levels of
      microorganisms colonizing root-form and plate-form implants. This study finds no
      significant increase in levels of putative peri-implant pathogens at root-form
      and plate-form implants sites in the first 12 months after prosthetic loading
      when maintained by monthly scaling.

PMID- 8997682
TI  - Porphyromonas gingivalis reduces mitogenic and chemotactic responses of human
      periodontal ligament cells to platelet-derived growth factor in vitro.
AB  - The effects of a sonicated Porphyromonas gingivalis ATCC 33277 protein extract on
      the mitogenic and chemotactic responses of human periodontal ligament (PDL) cells
      to the recombinant human platelet-derived growth factor-BB homodimer (PDGF-BB)
      were examined in vitro. Proliferation of PDL cells was inhibited by P. gingivalis
      extract at concentrations higher than 10 micrograms/mL protein. At 100
      micrograms/mL of P. gingivalis extract, cells did not proliferate. DNA synthesis
      in PDL cells, as revealed by [3H]-thymidine incorporation, was also inhibited by
      approximately 50% in the presence of 50 micrograms/mL P. gingivalis extract for
      24 hours. In contrast, PDGF-BB at 1 ng/mL enhanced DNA synthesis in PDL cells,
      followed by maximum enhancement at concentrations higher than 10 ng/mL PDGF-BB.
      However, this mitogenic response to PDGF-BB was markedly reduced in the presence
      of 20 micrograms/mL of P. gingivalis extract and did not reach the maximum level
      even if PDGF-BB concentrations were increased to 250 ng/mL. PDL cells exhibited a
      chemotactic response to PDGF-BB at 1 ng/mL, which was also inhibited by
      pretreatment of the cells with P. gingivalis extract at 10 to 50 micrograms/mL.
      Scatchard analysis of a [125I]-PDGF binding assay demonstrated that PDL cells
      have both high and low PDGF binding affinity sites. Treatment of the cells with
      P. gingivalis extract decreased the number of PDGF-binding sites to approximately
      35% of the control level, while it caused only a slight change in the affinities
      of both types of binding site. These results indicated that the P. gingivalis
      extract reduced mitogenic and chemotactic responses of human PDL cells, possibly
      through mechanisms involving a decrease in PDGF-binding capacity of these cells.
      Due to this inhibitory effect of P. gingivalis, the normal levels of PDGF in
      periodontal lesions may not be sufficient to promote periodontal regeneration
      through activation of PDL cell proliferation and migration. Therefore, the
      therapeutic use of PDGF-BB, as a supplement to pre-existing PDGF and as an
      adjunct, while also eliminating P. gingivalis from periodontal lesions, would
      help periodontal tissue regeneration.

PMID- 8997684
TI  - Attitudes to Papanicolaou smears.
AB  - Preventive health behavior has been defined as behavior aimed at the prevention
      or detection of disease in an asymptomatic state. When cervical cancer is
      discovered and treated in the premalignant stage, the cure rate is 95% or higher.
      The success of the screening program for cervical cancer depends at least
      partially on women's acceptance of and compliance with the service. Compliance is
      related to women's underlying motivation and attitudes to cervical cancer and
      health and illness in general. The following paper provides an overview of the
      literature and examines who participates in cervical screening, the participant's
      feelings about the test and the place of testing, who are unlikely to participate
      and the reasons for this noncompliance. It is hoped that this overview will
      indicate possible ways of improving women's acceptance of this screening, whilst
      identifying negative attitudes and experiences which impede participation.

PMID- 8997683
TI  - Regeneration of rat calvarial defects using a bioabsorbable membrane technique:
      influence of collagen cross-linking.
AB  - The aim of the present study was to examine the influence of cross-linking on
      collagen membranes used for guided bone regeneration of calvarial defects in
      rats. In 48 Wistar rats, divided equally into 4 groups, 1 control and 3
      experimental, standardized transosseous circular calvarial defects were made
      midparietally. In the control group, the defect was only covered by the soft
      tissue flap while in the 3 experimental groups, 3 differently cross-linked
      collagen membranes were interposed between the osseous defect and the overlying
      flap before suturing. The healing was assessed at 10, 20, and 30 days after
      surgery. The results showed that augmenting the degree of collagen cross-linking
      diminished the membrane resorption rate. Compared to the sham-operated sites, the
      membrane protected defects showed significantly more bone regeneration (on
      average 4 times more) as attested by histology and measured by histomorphometric
      analysis. Although the bone gain seemed to augment with increasing degrees of
      cross-linking, the results within the 3 experimental groups were not
      statistically different. Since longer healing periods might have been necessary
      to substantiate results within experimental groups, a study is currently
      undertaken to evaluate this aspect. This study demonstrated the efficacy of
      collagen membranes in guiding bone regeneration, as well as the importance of the
      type and degree of cross-linking.

PMID- 8997685
TI  - Connections between primary vaginismus and procreation: some observations from
      clinical practice.
AB  - So far, the literature on vaginismus has mainly been contemplative. Quantitative
      data are scarce, while fertility and obstetrical aspects are almost never
      considered. In this article, these two aspects are addressed. A cohort of
      patients received a questionnaire, developed to obtain information about possible
      connections between the vaginistic reaction, the patient's treatment goals and,
      if relevant, obstetrical characteristics. Our data reveal that the desire to have
      a child is not a negative predictor for treatment outcome in terms of
      consummation. In some instances, however, self-insemination, as a bedroom
      procedure, is an effective treatment option to enable the couple to reach their
      fertility goal. Some women will conceive without intercourse experience;
      according to our data, delivery in this group is hardly more problematic than in
      a group of women who, after treatment for vaginismus, conceived by sexual
      intercourse. Having delivered a child may have a slightly positive effect on the
      capability to have intercourse, but only in a minority. Obstetricians should be
      aware that not infrequently, women give birth who suffer from severe penetration
      phobias.

PMID- 8997686
TI  - The effects of relaxation response training on menopausal symptoms.
AB  - The specific aim of this study was to investigate the efficacy of elicitation of
      the relaxation response for the treatment of menopausal hot flashes and
      concurrent psychological symptoms. The volunteer sample consisted of 33 women,
      between the ages of 44 and 66 years, who were in general good health, with a
      minimum of 6 months without a menstrual period, experiencing at least five hot
      flashes per 24-h, and not using hormone replacement therapy. The setting was an
      outpatient clinic in a tertiary care teaching hospital. The interventions used
      were relaxation response training and an attention-control group and a daily
      symptom diary measuring both the frequency and intensity of hot flashes, the
      Spielberger State-Trait Anxiety Inventory (STAI), and the Profile of Mood Scale
      (POMS) were the measures used. This was a randomized, controlled, prospective
      study. Subjects were randomly assigned to one of three groups (relaxation
      response, reading, or control) for the 10-week study. The first 3 weeks of
      baseline measurement of frequency and intensity of hot flash symptoms, and the
      preintervention psychological scores were compared with the final 3 weeks
      measurement of frequency and intensity and the postintervention psychological
      scores for symptomatic improvement. The relaxation response group demonstrated
      significant reductions in hot flash intensity (p < 0.05), tension-anxiety (p <
      0.05) and depression (p < 0.05). The reading group demonstrated significant
      reductions in trait-anxiety (p < 0.05) and confusion-bewilderment (p < 0.05).
      There were no significant changes for the control group. Daily elicitation of the
      relaxation response leads to significant reductions in hot flash intensity and
      the concurrent psychological symptoms of tension-anxiety and depression.

PMID- 8997687
TI  - Repeat abortion: a comparative study.
AB  - In a study of 404 women (simple random sample) 20-29 years of age, 201 women
      (group A) applying for abortion and 203 women (group B) continuing their
      pregnancies were given a questionnaire and were also interviewed. The aim of the
      study was to describe women applying for repeat abortion and to compare them with
      women having their first abortion and with women continuing their pregnancies.
      Variables measured were socio-economic, psychological and social problems,
      relationship with the partner, earlier pregnancies, how the present pregnancy was
      experienced and decision-making. For presentation of the results, the data have
      been divided into four subgroups: pregnant women applying for their first
      abortion (A1, n = 137), women applying for repeat abortion (A2, n = 64), women
      continuing their pregnancies who have never applied for abortion (B1, n = 142),
      and women continuing their pregnancies who had previously applied for one or more
      abortions (B2, n = 58). Women who had had previous abortion/abortions had
      experienced more psychological problems during their lifetime than the other
      groups studied. They had more contact with the social welfare service and
      evaluated their relationship with the partner as less harmonious than women
      having a first abortion, also in comparison with women continuing their
      pregnancies with no earlier applications for abortion. Women who have had
      previous abortion/abortions seem to have a need for special attention. This
      involves not only being provided with efficient and acceptable contraception, but
      also with social and psychological support based on the experiences of the women.

PMID- 8997689
TI  - Psychotropic drug use by women: could violence account for the gender difference?
AB  - Cross-national studies show that the female to male ratio of psychotropic drug
      use is approximately 2:1. Twenty per cent of female general practice patients are
      prescribed psychotropic drugs. The reasons behind this remain unclear but
      research points to the higher levels of psychopathology either experienced or
      reported by women. Recent studies have shown a strong association between the
      experience of domestic violence and sexual abuse and the development of mental
      ill health. It may be that women who use psychotropic drugs represent a group who
      are more likely to be victims of violence. If this is the case then doctors
      should be incorporating questioning about violence when thinking of prescribing
      such drugs. Further research is necessary to clarify whether or not a
      relationship exists between psychotropic drug use by women and a previous or
      current history of physical or sexual abuse.

PMID- 8997688
TI  - The complexity of labor pain: experiences of 278 women.
AB  - All women giving birth over a period of 2 weeks in a major city of Sweden, except
      non-Swedish speaking women and those with elective Caesarean sections, were asked
      about their experience of pain 2 days after the birth. The sensory (pain
      intensity) and effective (negative or positive experience) dimensions of pain, as
      well as need for pain relief during labor were explored. The 278 women who
      returned completed questionnaires (91%) reported high levels of pain, 41% worst
      imaginable pain, in spite of wide use of pharmacological pain relief. Only 9% had
      no analgesia. Pain was not an entirely negative experience, 28% assessing it as
      more positive than negative, suggesting that coping with pain is a rewarding
      experience for some women. More than 30 different explanatory variables were
      included in regression analysis to explain the variation in pain intensity and
      pain attitude scores, but only five contributed to the respective model. Most of
      the variables explaining pain intensity, namely anxiety during labor, expected
      pain, expected birth experience, midwife support and duration of labor, differed
      from the variables explaining attitude to pain. These were pain intensity,
      anxiety, expected birth experience physical well-being during pregnancy and
      emergency Caesarean section. The explanatory values were relatively low,
      especially for the model explaining pain intensity (R2 = 15%). The findings are
      discussed in the light of the different character and meaning of childbirth pain
      compared with pain related to disease.

PMID- 8997690
TI  - Psychoanalytic group therapy in the treatment of severe psychosomatic
      dysfunctions--experiences since 1981.
AB  - As a gynecologist and analytical psychotherapist, I have been treating women
      suffering from severe psychosomatic gynecological dysfunctions in a semi-open
      psychoanalytic group since 1981. The duration of therapy is 2-3 years, and the
      success rate 85%. The subjective symptoms include chronic recurrent disorders of
      the urogenital tract in terms of urogenital resistance, chronic pelvic pain with
      no organic findings, pruritus vulvae, 'burning vulva' and premenstrual syndromes.
      These conditions are often associated with sexual dysfunctions, a disturbed
      experience of the body image and substantial relationship conflicts. All patients
      are suffering from a psychoneurosis on a broad structural basis, due
      psychogenetically to early unresolved triangulation.

PMID- 8997691
TI  - Biosynthesis of bacterial peptidoglycan.

PMID- 8997692
TI  - Comparative analysis of HSV-1 temperature mutants proteins and their reactivity.
AB  - Protein's characteristic of temperature sensitive (ts 28 degrees C) and
      temperature resistant (tr 39 degrees C) mutants and native HSV-1 strain was
      performed. Electrophoretic and Western-blott analysis of virus proteins and their
      reactivity tested by immunoenzymatic staining was the main subject of the
      presented paper. There were found no significant differences in the protein
      structure between native strain and its temperature clones in electrophoresis. It
      is important that slight differences observed in protein's antigenic reactivity
      of ts 28 degrees C (54 kDa) and tr 39 degrees C (99-100; 160 kDa), do not
      influence on the possible application of the mutants for immunization and
      challenging.

PMID- 8997694
TI  - The mechanism of bactericidal action of normal human serum against Salmonella
      rods.
AB  - Forty Salmonella strains sensitive to the bactericidal action of serum were
      investigated. All these strains were susceptible to complement activated by the
      classical pathway though in part (60%) of these strains the presence of lysozyme
      was necessary for killing. S. typhimurium rods were susceptible to only one
      mechanism of the action of bactericidal factors. On the contrary, S. enteritidis
      strains were sensitive to three various mechanisms of bactericidal action of
      serum. Next eight forms of Salmonella typhimurium LT2 differing with respect to
      the structure of LPS were studied. Original strain was a smooth, form S, and
      remaining strains were various rough (R) forms such as Ra, Rb1, Rb2, Rc, Rd1,
      Rd2, Re. The S form was susceptible only to the complete human serum what means
      that all bactericidal factors of serum were needed for killing. Ra form was
      susceptible to two independent bactericidal mechanisms: complement (C) activated
      by the alternative pathway in the presence of lysozyme and C activated
      simultaneously by both bactericidal C pathways without the participation of
      lysozyme (al, ac). The next form, Rb1, besides the mechanism mentioned above was
      also susceptible to C activated by the classical pathway in the presence of
      lysozyme (al, ac, cl). Other forms (Rb2, Rc, Rd1, Rd2, Re) were susceptible to
      three mechanisms (al, ac, cl) as well as to C activated by the classical pathway
      without lysozyme (c). The mechanism (c) was weakly efficient against forms Rb2
      and Rc and somewhat more efficient against Rd1 and Rd2 and the most efficient
      against Re.

PMID- 8997695
TI  - Enterotoxigenic Bacteroides fragilis isolated from nondiarrheic adults.
AB  - From 220 fecal samples of nondiarrheic adults, 29 strains of Bacteroides fragilis
      were isolated. Nine percent of them were enterotoxigenic Bacteroides fragilis
      (ETBF) strains. That is the first isolation of ETBF strains from nondiarrheic
      adults in Poland. Isolated ETBT strains could not be distinguished from non
      enterotoxigenic Bacteroides fragilis (NTBF) strains by means of agglutination
      test. The sensitivity to antimicrobial agents does not differentiate
      enterotoxigenic from nonenterotoxigenic B. fragilis strains.

PMID- 8997693
TI  - Studies of antibiotic resistance of rough and smooth Proteus mirabilis strains
      and influence of polymyxin E on their lipopolysaccharide composition.
AB  - The influence of type of bacterial culture media on antibiotic resistance of
      Proteus mirabilis R and S forms, was tested. P. mirabilis S1959 (S form), R45 and
      R110 strains (Re and Ra mutant, respectively) cultivated in media supplemented
      with 10% heat inactivated bovine serum were resistant to ampicillin, amoxicillin,
      nalidixic acid and nitroxoline. Proteus strains cultivated in media without serum
      were sensitive to these antibacterial agents. The presence of serum did not
      change the polymyxin E (colistin) resistance of there Proteus strains tested. The
      effects of the presence of colistin (1000 U/ml) in culture media on Proteus
      lipopolysaccharide composition was studied. The content of uronic acids and
      phosphate residues in lipopolysaccharides isolated from bacteria cultivated in
      the presence of colistin (LPS-col), were lower than in control LPSs. The contents
      of 4-amino-4-deoxy-L-arabinose decreases in S1959 LPS-col, increases in R110 LPS
      col and remains unchanged in R45 LPS-col. These results indicate that the
      presence of colistin in cultivation media exerts an influence on the contents of
      charged components of LPSs isolated from polymyxin E-resistant Proteus R and S
      strains.

PMID- 8997697
TI  - Sorption of cadmium by filamentous soil fungi.
AB  - The article presents the evaluation of the short-term sorption of Cd by selected
      soil fungi. The Freundlich adsorption isotherm method for metal sorption
      modelling was applied. Fungal strains belonging to two classes, Zygomycetes and
      Ascomycetes, were used. Altogether, six species from Ascomycetes (A. niger, A.
      nidulans, Ps. boydii, T. koningii, P. janthinellum, P. verrucosum) and three from
      Zygomycetes (R. rhizopodiformis, R. oryzae, R. pusillus) were examined. These
      fungi were selected for experiments due to the differences in their cell wall
      compositions. The walls of Ascomycetes and Zygomycetes are in the chitin-glucan
      and in the chitosan-chitin groups, respectively. It was found that the biomass of
      A. nidulans and R. pusillus displayed the relatively high Cd sorption capacity.
      The sorption of Cd was similar among the fungi investigated. The metal
      accumulation by these fungi increased with increasing concentrations of Cd. The
      binding of Cd to the fungal biomass was an extremely rapid process. During the
      first 5 minutes, 72.75% of Cd was taken up by the fungal biomass. The fungal Cd
      sorption was increased in low pH (range from 3 to 5).

PMID- 8997696
TI  - Detection of enterotoxigenic Bacteroides fragilis (ETBF), among strains isolated
      between 1976 and 1995 in Poland.
AB  - Thirty five Bacteroides fragilis strains isolated from different, clinical
      specimens in 1976-1985 and in 1995, preserved in strains collection of Department
      of Clinical Bacteriology were studied. The cytotoxicity of 35 bacterial culture
      supernatants, were tested on the human carcinoma cell line HT29/C1. Two strains
      proved to be enterotoxigenic. One of those strains was isolated in 1985 from the
      human, before the existence of enterotoxin producing strain was reported. All 35
      strains were metronidazol sensitive showing lack of correlation between
      enterotoxigenicity and metronidazol resistance.

PMID- 8997698
TI  - Phage types and plasmid profiles of Salmonella enteritidis strains.
AB  - 112 strains of Salmonella enteritidis were tested according to phage typing
      method and plasmid profile analysis. 66 strains were classified as PT4, 29
      strains as PT6 and 17 strains as PT10. The strains were differentiated into 17
      groups according to plasmid profiles.

PMID- 8997699
TI  - Illusions of well-being and the repressive coping style.
AB  - Recently, the proposition that it is normal for people to see themselves in
      illusorily positive terms has been challenged and it has been suggested that this
      phenomenon may be explained by the contribution of subgroups of overly positive
      individuals. We investigated this possibility by examining the contribution of
      repressive individuals, who tend to avoid negative affect, to the illusions of
      unrealistic optimism and overly positive self-evaluations. Whereas normal and non
      anxious controls showed no evidence of illusory biases, repressors rated
      themselves as significantly less likely than the average person to experience
      negative events, and rated negative words as significantly less descriptive of
      self than others. These findings support the hypothesis that, in judgements
      involving negative material, the presence of repressors may be contributing to
      findings of illusory biases.

PMID- 8997700
TI  - Repressive coping style and the architecture of emotion-related memories: is
      their relationship that simple?
AB  - The present study re-examines the relationship between repressive coping style
      and the architecture of emotion-related memories by introducing methodological
      improvements in the elicitation of these memories. Participants were classified
      into four repressive coping groups according to the Taylor Manifest Anxiety scale
      and the Marlowe-Crowne Social Desirability scale. They were then asked to recall
      personal experiences related to five core relational themes attempting to elicit
      positive and negative emotions and to rate how they felt in each situation.
      Results indicated that differences in the architecture of emotion-related
      memories among the four repressive coping groups depended on the type of the
      elicited memory. The discussion emphasizes the complexity of the relationship
      between repressive coping style and the architecture of emotion-related memories
      and suggests an expansion of the concept of repression.

PMID- 8997701
TI  - Nursing staff responses to violent events in closed psychiatric wards: a
      comparison between attributional and cognitive-neo-associationistic analyses.
AB  - This paper examines the behavioural response of nursing staff in psychiatric
      wards to a patient's violent behaviour towards a staff member as a function of
      whether the patient's behaviour was presented as arbitrary or not. The
      participants were 133 nurses. They were given two vignettes describing an
      arbitrary and a non-arbitrary behaviour of a patient and were asked what the
      typical response in their ward to each event would be. The results show that when
      the patient's behaviour was perceived as arbitrary, staff was believed to respond
      with a therapeutic reaction more frequently than to non-arbitrary behaviour.
      Moreover, participants' professional characteristics played a greater role in the
      non-arbitrary scenario. It is suggested that a therapeutic response to a
      patient's violent behaviour requires a recognition that the patient's behaviour
      is consistent with his/her role as a patient. The implication of these results
      for Berkowitz & Heimer's (1989) cognitive-neo-associationistic analysis is
      discussed.

PMID- 8997702
TI  - Microbial ribulose 1,5-bisphosphate carboxylase/oxygenase: a molecule for
      phylogenetic and enzymological investigation.
AB  - Ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) catalyzes the key
      reaction of the Calvin reductive pentose phosphate cycle and as such is
      responsible for life as we know it. This enzyme has been intensively studied for
      decades. Evidence that RubisCO phylogenies are incongruent with those derived
      from other macromolecules has been accumulating and recent discoveries have
      driven home this point. Here we review findings regarding RubisCO phylogeny and
      discuss these in the context of the important biochemical and structural features
      of the enzyme. The implications for the engineering of improved RubisCO enzymes
      are considered.

PMID- 8997703
TI  - The methanol oxidation genes mxaFJGIR (S) ACKLD in Methylobacterium extorquens.
AB  - MxaJ is a protein of unknown function encoded by mxaJ in the mxaFJGI operon. We
      have constructed a mxaJ mutant of M. extorquens with a deletion which does not
      affect transcription of downstream genes. It contained cytochrome cL (MxaG), but
      neither subunit of methanol dehydrogenase (MxaF and MxaI). MxaJ is probably
      involved in processing this enzyme. We have sequenced the region between mxaFJGI
      and five other methanol oxidation genes, mxaACKLD; it includes one open reading
      frame (mxaR) and a possible second open reading frame (mxaS), demonstrating the
      presence in M. extorquens of the following gene cluster: mxaFJGIR(S) ACKLD.

PMID- 8997704
TI  - Ca(2+)-transporting ATPase(s) of the reticulum type in intracellular membranes of
      Saccharomyces cerevisiae: biochemical identification.
AB  - Several lines of evidence are presented to show that the Ca(2+)-ATPase activity
      of total yeast membranes is due to the reticulum (R) type of Ca(2+)-ATPase: (1)
      Neither calmodulin nor low concentrations of calmodulin antagonists change Ca2+
      uptake; (2) removal of plasma membranes (PM) following Con A treatment of
      spheroplasts (SP) does not significantly alter Ca2+ uptake by the remaining
      membranes, but increases its specific activity 3.5-fold; (3) after incubation of
      membranes with [gamma-32P]ATP, SDS-PAGE shows the formation of acyl phosphate
      intermediates with molecular masses of around 100, 180-190 and 205 kDa; formation
      of these acyl phosphates requires Ca2+ and is blocked by cyclopiazonic acid, La3+
      ions and in the absence of Ca2+. The data on fractionation of yeast membranes are
      consistent with the suggestion that both the ER and the Golgi are equipped with
      Ca(2+)-ATPase(s).

PMID- 8997705
TI  - Discrimination between Bacillus cereus and Bacillus thuringiensis using specific
      DNA probes based on variable regions of 16S rRNA.
AB  - Identification of Bacillus cereus and differentiation between B. cereus and
      closely related species are currently based on biochemical tests. The main
      problem is to discriminate between B. cereus and B. thuringiensis. Sequencing
      part of the 16S rRNA showed that several B. cereus isolates present in food and
      involved in food poisoning, confirmed according to the classical biochemical
      methods, were in fact B. thuringiensis. As this organism is the most commonly
      used microbial insecticide worldwide, the results of this study emphasize the
      need for accurate identification methods and for careful screening of strains for
      use as insecticides. Therefore, specific DNA probes based on the variable region
      VI of 16S rRNA of B. cereus and B. thuringiensis were designed. The probes were
      used in hybridization experiments with the variable region amplified using the
      polymerase chain reaction. In this way, a rapid and sensitive method was
      developed to distinguish B. cereus and B. thuringiensis.

PMID- 8997706
TI  - Purification and properties of citrate synthase from Acetobacter europaeus.
AB  - Citrate synthase (EC 4.1.3.7) was purified from the acidophilic bacterium
      Acetobacter europaeus to electrophoretic homogeneity. The specific activity was
      228 units/mg of protein during the exponential ethanol-oxidation growth phase.
      The enzyme has a molecular mass of 280 kDa and is a hexamer with a subunit size
      of 46 kDa. The apparent K(m) values were 20 microM for oxaloacetate and 51 microM
      for acetyl-CoA. Unlike citrate synthase from other Gram-negative bacteria, the
      activity of the enzyme was inhibited by ATP, slightly enhanced by ADP and not
      effected by NADH. Acetate caused activation of the enzyme. The pH optimum on the
      citrate synthase activity in vitro was 8.1. The amino-terminal amino acid
      sequence of the purified enzyme was ENGKSATISLNGKDVALPVL.

PMID- 8997707
TI  - Mycocinogeny in the genus Bullera: taxonomic specificity of sensitivity to the
      mycocin produced by Bullera sinensis.
AB  - A strain of Bullera sinensis that secretes a fungicidal thermolabile and protease
      sensitive toxin was found. Its killer phenotype was cureless. Ascomycetous,
      ustilaginaceous yeasts and the members of the Sporidiales are insensitive to the
      B. sinensis killer toxin. The mycocin acts against tremellaceous yeasts only,
      except for Cystofilobasidium, Fellomyces and Trichosporon spp. The genera Mrakia,
      Bullera, Cryptococcus and Udeniomyces are heterogeneous in sensitivity pattern.
      The different responses of some anamorphic species to this mycocin are often
      consistent with the origin of the strains and the differences in sexual,
      chemotaxonomic and physiological characteristics between them.

PMID- 8997708
TI  - Thermotolerance and trehalose accumulation induced by heat shock in yeast cells
      of Candida albicans.
AB  - Candida albicans yeast cells growing exponentially on glucose are extremely
      sensitive to severe heat shock treatments (52.5 degrees C for 5 min). When these
      cultures were subjected to a mild temperature preincubation (42 degrees C), they
      became thermotolerant and displayed higher resistance to further heat stress. The
      intracellular content of trehalose was very low in exponential cells, but
      underwent a marked increase upon non-lethal heat exposure. The accumulation of
      trehalose is likely due to heat-induced activation of the trehalose-6-phosphate
      synthase complex, whereas the external trehalase remained practically unmodified.
      After a temperature reversion shift (from 42 degrees C to 28 degrees C), the pool
      of trehalose was rapidly mobilized without any concomitant change in trehalase
      activity. These results support an important role of trehalose in the mechanism
      of acquired thermotolerance in C. albicans and seem to exclude the external
      trehalase as a key enzyme in this process.

PMID- 8997709
TI  - A cluster of atypical Yersinia strains with a distinctive 16S rRNA signature.
AB  - Thirty-eight bacterial isolates from raw milk samples in Queensland, Australia
      were identified as members of the genus Yersinia on the basis of biochemical
      profile, ability to hybridize with a genus-specific DNA probe, comparative 16S
      rDNA sequence analysis, and the presence of characteristic 16S rDNA signature
      nucleotides which occur in all Yersinia spp. Twenty-five of these isolates
      reacted with typing sera (O:22 or O:58) of Y. enterocolitica; the remainder were
      non-typable. None of the isolates displayed any of the phenotypic or genetic
      virulence-associated characteristics of Y. enterocolitica. Comparative 16S rDNA
      sequence analysis revealed that members of this group appear to represent a new
      sub-line within the genus Yersinia, most closely related to Y. frederiksenii
      hybridization group 2 (unnamed genomospecies 2). This findings was confirmed by
      DNA hybridization studies which indicated that the strains belonged to the
      unnamed genomospecies, Yersinia frederiksenii genomospecies 2, which is
      biochemically indistinguishable from Y. frederiksenii (Y. frederiksenii
      genomospecies 1). A 23-nucleotide 16S rDNA signature stretch which characterised
      these strains was identified.

PMID- 8997710
TI  - On the amine oxidases of Klebsiella aerogenes strain W70.
AB  - Klebsiella aerogenes W70 was reported previously to produce a membrane-associated
      tyramine oxidase (TynA) that did not act on 2-phenylethylamine. Subsequently, a
      gene cloned from K. aerogenes W70 produced a soluble amine oxidase (MaoA) that
      acted readily on 2-phenylethylamine and tyramine. This enzyme appeared to be
      equivalent to a 2-phenylethylamine oxidase of Escherichia coli K-12 (MaoA) but
      was assumed to be the originally described K. aerogenes W70 tyramine oxidase
      (TynA). However, as described here, whole cells and cell-free extracts of K.
      aerogenes W70 showed only the tyramine oxidase (TynA) that is inactive against 2
      phenylethylamine and not the maoA gene product. It seems that the organism has
      two amine oxidase genes, tynA and maoA, but only tynA is expressed. Hence, data
      relating to the expression of the K. aerogenes W70 tynA gene cannot be assumed to
      apply to the maoA gene of E. coli K-12 because they encode different enzymes.

PMID- 8997711
TI  - Construction of an epitope vector utilising the diphtheria toxin B-subunit.
AB  - An immunogenic loop within the diphtheria toxin has been deleted from the B
      subunit by a modification of the inverse polymerase chain reaction (IPCR) and
      replaced by a unique restriction endonuclease site. An oligonucleotide encoding
      an identified epitope sequence from the major outer membrane protein of Neisseria
      meningitidis of similar size and structure to that deleted has been introduced
      into the restriction site. Expression of the resulting chimeric B-subunit from
      Escherichia coli yielded a protein that was recognised by a panel of antibodies
      specific for the meningococcal epitope. Initial immunisation data suggest that
      this protein could elicit an antibody response against both diphtheria toxin and
      meningococcal proteins.

PMID- 8997712
TI  - Thermostable xylanases produced at 37 degrees C and 45 degrees C by a
      thermotolerant Aspergillus strain.
AB  - Differences between xylanases produced by Aspergillus FP-470 growing under normal
      (37 degrees C) and temperature stress conditions (45 degrees C) were evaluated.
      Fungal growth at 45 degrees C was seriously affected. However, the xylanase
      specific activity was 2.5 times higher than that produced at 37 degrees C.
      Optimum pH and temperature were 6.5, 80 degrees C and 4.3, 50 degrees C for the
      xylanases produced at 37 degrees C and 45 degrees C, respectively.
      Electrophoresis showed that a more complex xylanolytic system was produced at 37
      degrees C. Stress induced by temperature produced a decrease in the number of
      extracellular xylanases released by fungi, but increased the production of some
      xylanases, possibly essential for growth under stress conditions.

PMID- 8997713
TI  - Involvement of iclR and rpoS in the induction of acs, the gene for acetyl
      coenzyme A synthetase of Escherichia coli K-12.
AB  - Two independent pathways in Escherichia coli convert acetate to acetyl CoA:
      reversal of acetate production by phosphotransacetylase and acetate kinase, and
      the acetyl-CoA synthetase (Acs) pathway that scavenges acetate. We investigated
      acs gene expression by using a cat transcriptional fusion. It was observed that
      acs expression varies depending on the carbon sources used and occurs in the
      stationary phase of growth even in the absence of acetate. Mutations in iclR for
      the repressor of the glyoxylate shunt and in rpoS for the stationary phase sigma
      factor reduced the consumption of acetate mediated by Acs, indicating that both
      are involved in acs regulation.

PMID- 8997714
TI  - Cloning of a new FLO gene from the flocculating Saccharomyces cerevisiae IM1-8b
      strain.
AB  - A flocculation conferring gene was cloned from a genomic library of the
      flocculating strain Saccharomyces cerevisiae IM1-8b as a 5 kb DNA fragment. The
      shortest DNA fragment (XbaI-XbaI) able to confer the flocculating phenotype was
      3.1 kb. Southern analysis revealed that this gene was not homologous to the
      already reported FLO1 gene since strong hybridization signals were obtained when
      chromosomes IV and XII were probed with a digoxygenin-labelled fragment and no
      signal at all was detected for chromosome I. Partial sequencing data
      unequivocally ascribed the cloned fragment to chromosome XII. The gene was
      detected in a variety of S. cerevisiae strains regardless of their being
      phenotypically flocculating. This gene which, we propose as FLO2, is able to
      complement the flo1 mutation and is suppressed by suppressors (fsu3) that do not
      affect other FLO genes.

PMID- 8997715
TI  - Immunological and functional comparison between Clostridium perfringens iota
      toxin, C. spiroforme toxin, and anthrax toxins.
AB  - Clostridium perfringens iota and C. spiroforme toxins consist of two separate
      proteins. One is the binding component and the other the enzymatic component. The
      two toxins secreted by Bacillus anthracis are composed of binary combinations of
      three proteins: protective antigen, lethal factor, and edema factor. As shown by
      Western blotting and ELISA, the binding component of anthrax toxin shares common
      epitopes with that of iota toxin and C. spiroforme toxin which are closely
      related immunologically. However, no functional complementation was observed
      between iota toxin and anthrax toxin components. The binding components can form
      toxins active on macrophages only in combination with their respective enzymatic
      components. Agents which prevent acidification of endosomes do not have the same
      effects on anthrax toxin activity as they do on iota and C. spiroforme toxins.
      Therefore, the mechanisms of entry into the cells are presumably different. Since
      the binding components of anthrax toxins and iota toxin share a conserved
      putative translocation domain, these binding components could have a common mode
      of insertion into the cell membranes.

PMID- 8997716
TI  - Virulence properties of Escherichia coli O111:H12 strains.
AB  - Seventeen Escherichia coli O111:H12 strains isolated from the feces of children
      with acute diarrhea were studied with regard to their adherence properties and
      other virulence characteristics. All strains showed an aggregative adherence
      pattern to HEp-2 cells and agglutinated bovine and sheep red cells in the
      presence of mannose. These strains did not have gene sequences homologous to the
      aggregative adherence fimbria I gene and did not react with any of the DNA probes
      used to detect other virulence genes in enteropathogens. With one exception, the
      O111:H12 strains did not induce fluid accumulation in the rabbit ileal loop
      assay, although 16 of the strains had the enteroaggregative E. coli heat-stable
      enterotoxin 1 (EAST) gene sequences. A 60-70 MDa plasmid was present in 16 of the
      strains studied. We conclude that the O111:H12 serotype, one of the first E. coli
      identified in infantile diarrhea, belongs to the enteroaggregative E. coli
      category but the genes encoding its adherence phenotype are distinct from those
      previously described.

PMID- 8997717
TI  - Presence of F420-dependent glucose-6-phosphate dehydrogenase in Mycobacterium and
      Nocardia species, but absence from Streptomyces and Corynebacterium species and
      methanogenic Archaea.
AB  - A range of organisms known to contain F420 or to be relatives of mycobacteria
      were examined for F420-dependent glucose-6-phosphate dehydrogenase (FGD) and NADP
      dependent glucose-6-phosphate dehydrogenase (NADP-G6PD) activities. All free
      growing Mycobacterium species examined (including a virulent Mycobacterium
      tuberculosis strain) had FGD activities of 0.014-0.418 mumol min-1 mg protein-1,
      and NADP-G6PD activities of 0.013-0.636 mumol min-1 mg-1. Armadillo-grown
      Mycobacterium leprae had FGD activity of 0.008 mumol min-1 mg-1, but no
      detectable NADP-G6PD activity. Nocardia species also had FGD activity (0.088
      0.154 mumol min-1 mg-1). Streptomyces and Corynebacterium species had no FGD, but
      had NADP-G6PD. Methanogenic Archaea had neither activity.

PMID- 8997718
TI  - Expression of the heme biosynthetic pathway genes hemCD, hemH, hemM, and hemA of
      Escherichia coli.
AB  - Little is known about the control of latter steps of heme biosynthesis in
      Escherichia coli. In this study we examined the transcriptional regulation of
      genes that encode two intermediate heme pathway enzymes, porphobilinogen
      deaminase (hemC) and uroporphyrinogen III cosynthase (hemD), and the final enzyme
      of the pathway, ferrochelatase (hemH). We also reexamined the regulation of hemA
      and the gene located immediately upstream of hemA, hemM. The regulatory regions
      of hemC, hemH, hemA and hemM were fused to lacZ. The resultant operon fusions
      were inserted into the E. coli chromosome in single copy and expression monitored
      under conditions of oxygen and heme limitation. Expression of hemM appeared
      constitutive under the conditions tested here. In contrast, expression of hemCD,
      hemH and hemA were shown to be mildly regulated in response to heme availability.
      Thus, transcription of four of the nine genes of the E. coli heme pathway appears
      to be only mildly regulated in response to heme limitation.

PMID- 8997719
TI  - A novel plasmid-encoded phage abortive infection system from Lactococcus lactis
      biovar. diacetylactis.
AB  - A 16-kb plasmid (pND859) was identified from Lactococcus lactis biovar.
      diacetylactis UK12922 which encodes phage resistance to the small isometric phage
      712 when tested in L. lactis LM0230. The gene encoding phage abortive infection,
      designated abi-859, was localized on a 1.2-kb region which consists of an open
      reading frame (ORF) of 846 bp preceded by a potential ribosome-binding site and a
      putative promoter region. A helix-turn-helix region typical of DNA-binding motifs
      was identified near the N-terminal of the abi-859 product, suggesting a possible
      interaction with the phage DNA.

PMID- 8997720
TI  - The regulatory effect of fermentable sugar levels on the production of leukotoxin
      by Actinobacillus actinomycetemcomitans.
AB  - The relationship between sugar availability and RTX (repeats in toxin) cytotoxin
      (leukotoxin) production in the periodontopathic bacterium, Actinobacillus
      actinomycetemcomitans, was investigated using a chemostat. A
      actinomycetemcomitans 301-b produced significant amounts of leukotoxin in
      anaerobic fructose-limited chemostat cultures at a dilution rate of 0.15 h-1 and
      at pH 7.0. When the growth limitation was relieved by pulsing the cultures with
      50 or 150 mM fructose (final concentrations), leukotoxin production immediately
      stopped and the amount of cellular leukotoxin decreased until the culture was
      returned to fructose-limited conditions. Leukotoxin synthesis was also repressed
      in the chemostat cultures by pulsing with glucose but not with the non
      fermentable sugar analog, alpha-methyl-D-glucoside. Leukotoxin production was
      also repressed by fructose in chemostat cultures of ATCC 33384, which is
      generally recognized as a non-leukotoxin-producing or minimally leukotoxic
      strain.

PMID- 8997721
TI  - Recent advances in the residue analysis of N-methylcarbamate pesticides.
AB  - This paper highlights recent advances in the determination of methylcarbamate
      residues in water, soil and plant tissues. Chromatographic analyses (e.g., HPLC,
      GC, supercritical fluid chromatography and TLC) with various sample pretreatment
      procedures and detection methods are reviewed. More generally, some non
      chromatographic techniques such as immunoassay, biosensor and spectrophotometry
      are included.

PMID- 8997722
TI  - Chromatographic techniques in the analysis of organochlorine pesticide residues.
AB  - The review briefly covers the chromatographic techniques used in the analysis of
      organochlorine pesticide residues. The organochlorines ranging from DDT, HCH, the
      cyclodiene group and the polychloroterpene group have been covered. It endeavours
      to examine the existing methodologies and techniques including residue
      extraction, clean-up, chromatographic procedures involved in clean-up and
      determination and quantification of organochlorine residues by gas liquid
      chromatography from different substrates like food commodities, crops, soil and
      water.

PMID- 8997723
TI  - Screening and analysis of polar pesticides in environmental monitoring programmes
      by coupled-column liquid chromatography and gas chromatography-mass spectrometry.
AB  - Screening and analysis of polar pesticides based on coupled-column reversed-phase
      liquid chromatography (LC-LC) and GC- or LC-MS is a powerful tool in the
      execution of environmental monitoring programmes. This paper presents a unified
      approach utilising LC-LC screening followed by GC-MS confirmation. As polar
      pesticides are not generally amenable to GC a widely applicable derivation
      technique is used. The results demonstrate that the proposed LC and MS techniques
      are capable of analysing a wide range of polar pesticides down to levels of 0.1
      microgram/l (EU limit for drinking water). LC switching techniques for group
      analysis or individual compounds rely on the reversed-phase retention and the UV
      detectability of the pesticides in combination with the choice of the LC columns.
      Fast miniaturised derivatization prior to GC-MS forms an integral part in the
      proposed strategy. In order to avoid extraction losses, derivation in the aqueous
      sample, preferably with electrophoric reagents with enhanced sensitivity in GC
      NICI-MS are employed where possible. In this communication, method development
      and validation fitting in the strategy are evaluated and the results of the
      combined approach are discussed.

PMID- 8997724
TI  - Occurrence and determination of pesticides in natural and treated waters.
AB  - Pesticides as environmental pollutants are described in detail along with their
      sources and paths of entry into various elements of the environment.
      Comprehensive literature data on the concentration of these pollutants in natural
      and treated waters and wastewaters are discussed. A wide selection of isolation
      and preconcentration techniques for these pollutants in water is presented and
      discussed. An emphasis is put on solid-phase extraction. In the case of the
      authors' work, a more detailed description is given.

PMID- 8997725
TI  - Strategies for chromatographic analysis of pesticide residues in water.
AB  - A review is presented of the modern techniques and approaches in methods for
      pesticide residue analysis in water matrices. The state of the art of the
      individual steps (extraction, clean-up, separation, identification, quantitation)
      of the chromatographic methods is reviewed with emphasis laid on emerging
      techniques which have gained popularity. The new approaches are discussed with
      respect to their relevancy to the requirements for increasing the sensitivity of
      detection and reliability of identification and quantitation at low levels of
      concentrations, arising from the European Community Drinking Water Directive.

PMID- 8997726
TI  - Analysis of pesticides in environmental water samples by solid-phase micro
      extraction-high-performance liquid chromatography.
AB  - Solid-phase micro-extraction (SPME) followed by high-performance liquid
      chromatography (LC) has been applied to analyze pesticides in water samples. A
      device interfaces SPME to the LC injection process by solvent extracting analytes
      from the fiber and then introducing the solvent into the LC injector. LC analysis
      with UV detection was performed first with a conventional column (4.6 mm I.D.).
      To enhance efficiency of SPME, three extraction conditions, stirring, temperature
      and salt concentration, were optimized. Subsequently, semi-microcolumn LC (1.5 mm
      I.D.) was evaluated for this method, giving lower detection limits and less
      solvent consumption. Detection limits were within Japanese regulatory limits for
      drinking water. The SPME-LC method was applied to real-world environmental water
      samples.

PMID- 8997727
TI  - Determination of pesticide residues in fruit and vegetables.
AB  - A review concerning the determination of pesticide residues in fruit and
      vegetables is presented. The basic principles and recent developments in the
      extraction and quantitation of pesticides are discussed. Consideration is given
      to solid phase and supercritical extraction techniques, automation and robotic
      systems, and immunoassay procedures.

PMID- 8997728
TI  - Official multiresidue methods of pesticide analysis in vegetables, fruits and
      soil.
AB  - Many different types of pesticides are used extensively on fruits and vegetables.
      The present contribution represents an overview of the multiresidue methods of
      analysis of the most widely used pesticides.

PMID- 8997729
TI  - Determination of cereal herbicide residues in environmental samples by gas
      chromatography.
AB  - Gas chromatographic analysis of cereal herbicide residues in water, soil, plant
      and air is reviewed. Herbicides widely used in spring and winter cereals, i.e.,
      phenoxyacids, benzonitriles, ureas, triazines, dinitroanilines, chloroacetamides
      and thiocarbamates, are considered. The main procedures used in the residue
      analysis, extraction, clean-up, derivatization and gas chromatographic
      determination are summarized and discussed.

PMID- 8997730
TI  - Chromatographic methods for the determination of pyrethrin and pyrethroid
      pesticide residues in crops, foods and environmental samples.
AB  - An overview is given of current progress in the analysis of pyrethrin and
      pyrethroid pesticide residues in crops, foods and environmental matrices.
      Extraction and clean-up are considered as the sample pretreatment prior to the
      determination. The conventional procedures (liquid-liquid partition and column
      chromatography) as well as the newly developed methods (solid-phase extraction,
      supercritical fluid extraction) are reviewed. GLC, HPLC and TLC chromatographic
      methods as the final determination of individual pyrethrin and pyrethroid
      residues and multi-residue, the enantiomer and diastereomer separation as well as
      the GC-MS confirmation are discussed and summarized in tabular form.

PMID- 8997731
TI  - Pesticide residue analyses in plant material by chromatographic methods: clean-up
      procedures and selective detectors.
AB  - This paper deals with the analysis of pesticide residues by chromatographic
      methods in samples of plant origin. Emphasis is put on the isolation and clean-up
      steps of the sample preparation for GC or LC determination. The problems of the
      extraction solvent selection and clean-up procedures using different types of
      adsorption column chromatography or gel permeation chromatography are discussed.
      Attention is also given to alternative techniques such as supercritical fluid
      extraction (SFE), matrix solid-phase dispersion (extraction) (MSPD) and sweep co
      distillation that are used for sample processing prior to GC and LC analysis.
      Currently, pesticide residue analyses are typically multi-residue procedures with
      highly sensitive methods. Consumption of costly and toxic solvents is being
      minimized and fully automated analytical procedures can be expected in the
      future.

PMID- 8997732
TI  - Pesticide residue analysis in fresh produce by gas chromatography-tandem mass
      spectrometry.
AB  - GC-MS-MS was used to analyze for multiple pesticide residues in fresh fruits and
      vegetables. Nineteen pesticides, including fungicides, herbicides,
      organophosphorus insecticides and chlorinated insecticides were spiked into seven
      different fruit and vegetable matrices and analyzed. The specificity of GC-MS-MS
      provided for low detection limits (ranging from 1-5 ppb) and unambiguous spectral
      confirmation for the target compounds in these complex matrices. Good precision
      was obtained (RSD values ranged from 1 to 9%), even at the 10 ppb level, without
      extensive sample clean-up steps.

PMID- 8997733
TI  - Analysis of pesticide residues in drinking water by planar chromatography.
AB  - Planar chromatography is described in the field of water analysis. The principle
      of automated multiple development (AMD) technique is mentioned, the strategy of
      the whole procedure which became a German standard is demonstrated and
      separations of pesticide mixtures, as well as water samples containing pesticides
      are presented. The suitability of this method was proved for 283 pesticides and
      the corresponding ISO Standard has been applied for.

PMID- 8997734
TI  - Complementation of direct-injection high-performance liquid chromatography and
      enzyme-linked immunosorbent assay for the analysis of thiabendazole in fruit
      juices and concentrates.
AB  - The fungicide thiabendazole was quantified in fruit juices and their concentrates
      (bulk and store bought) without clean-up by simply injecting 50 microliters of
      dissolved sample into an HPLC. This novel method used a mobile phase consisting
      of acetonitrile-methanol-water-ethanolamine (37:11:52:0.02) and was passed
      through a C18 column at 1 ml/min. Detection was accomplished by fluorescence at
      305 nm excitation and 345 nm emission. Using peak height thiabendazole was linear
      from 0.032 to 2.05 ng injected. The limit of quantitation was 5 ppb for juices
      and store concentrates (2.0 ppb for the limit of detection), 10 ppb for bulk
      apple concentrates and 25 ppb for other bulk concentrates (5 and 10 ppb,
      respectively for the limit of detection). Intra- and interassay percent relative
      standard deviations for standards and samples were mostly below 7% with none
      above 9%. Eighty-four juices and concentrates out of 200 analyzed were found to
      contain thiabendazole (2-2560 ppb) by HPLC and all were shown to be thiabendazole
      positive by enzyme-linked immunosorbent assay (ELISA). The HPLC vs. ELISA
      correlation coefficient was 0.984.

PMID- 8997735
TI  - Optimization of a matrix solid-phase dispersion method for the analysis of
      pesticide residues in vegetables.
AB  - A multiresidue method based on matrix solid-phase dispersion (MSPD) is studied to
      determine chlorfenvinfos, chlorpyrifos, fenarimol, iprodione, procimydone,
      propiconazole, tetradifon, triadimefon and vinclozolin in artichokes, green
      beans, lettuces and tomatoes. Alumina, silica and Florisil were assessed as
      extracting phases, and the extracts from Florisil were the cleanest. To
      facilitate manual extraction, sand was added to the sample together with the
      dispersing phase. Three eluting systems were then studied, and dichloromethane
      proved to be the best. Further purification can be performed using solid-phase
      cleanup after diluting extracts with aqueous solutions. Octyl- and octadecyl
      silica, modifications of the aqueous diluted extracts and several eluting
      solvents were studied. Determination was done by capillary gas chromatography
      (GC) with electron-capture detection, and confirmed by GC-MS using the electron
      impact mode and the selected ion monitoring. The proposed MSPD method was used to
      analyze 48 samples taken in the course of a year. Procymidone, vinclozolin,
      chlorpyrifos and chlorfenvinfos were identified in 10 samples at levels below the
      maximum residue levels allowed by the Spanish Government.

PMID- 8997736
TI  - Application of porous carbon for solid-phase extraction of dicarboxyimide
      fungicide residues from wines in combination with high-resolution capillary gas
      chromatography and gas chromatography-mass spectrometry.
AB  - Solid-phase extraction with a novel porous carbon sorbent CARB GR was used for
      the clean-up step of dicarboxyimide fungicides residues from variety of Slovak
      grape wines with subsequent capillary gas chromatography-flame ionization
      detection, -electron-capture detection (ECD) and -mass spectrometry-ion-trap
      detection (MS-ITD) analysis. Recovery was tested at various concentration levels
      of vinclozolin and iprodione in standard solutions (R = 80-97%, R.S.D. < or = 5).
      The value of recovery in spiked wines is dependent on concentration level
      (studied in the range of 5.9 micrograms/1-1.96 mg/l) and on the variety of wine
      (R = 80-96%; R.S.D. = 3-5%). Limits of quantitation (for sample volume 50 ml)
      were determined to be with GC-ECD for both fungicides in ppt range and with GC-MS
      ITD in the multiple ion detection mode monitoring in ptt range for vinclozolin
      and ppb range for iprodione. Concentration levels of vinclozolin residues were
      determined in treated wines (with 0.1% Ronilan 50 WP) as well as iprodione
      residues (with 0.15% Rovral 50 WP) and a strong dependence on the protective term
      before the harvest is shown.

PMID- 8997737
TI  - Off-line high-performance liquid chromatography and solid-phase extraction clean
      up for confirmation of pesticide residues in fresh produce by gas chromatography
      mass spectrometry.
AB  - GC-MS or GC-IT in conjunction with the GC-ECD, GC-FPD and HPLC Post-Column
      Derivatization for multiresidue scan analyses is a great complementary instrument
      for identification or confirmation purposes. However, MS in EI mode serves as a
      non-selective detector that is easily susceptible to interference by produce
      matrices in trace level residue analysis. The development of an effective clean
      up method is essential. In this research, a combination of HPLC/C18 and
      SPE/Florisil clean-up methods were used to reduce matrices in 10 commodities.
      Using the PBM system, the reference spectra of the computerized Anaheim data base
      were fingerprint matched to the fortified residues at the 50 ppb level. For most
      commodities, the PBM quality value was above 90% with the exception of whole
      oranges. The study demonstrates that the produce matrix of individual commodities
      varies considerably. The method met difficulties in the analysis of citrus due to
      the citrus peels. Although the method is commodity dependent, the clean-up
      procedure has reduced matrix interference in most cases. Efficiency is
      approximately in a range of 10(5) to 10(6) times, thus the method is effective in
      confirming trace level pesticide residues in fresh produce.

PMID- 8997738
TI  - Identification of pesticide poisoning in wildlife.
AB  - The Wildlife Incident Investigation Scheme investigates incidents of suspected
      poisoning of wildlife (also honey bees and companion animals) by pesticides in
      the United Kingdom. The approach to these investigations has evolved over the
      past 30 years. Field investigations, post-mortem examinations, toxicological data
      and experience of previous poisoning incidents assist in the selection and
      interpretation of appropriate chemical analyses. Several 'multi-residue' and
      several 'individual compound' analytical methods for pesticides in wildlife are
      currently in use; these are described.

PMID- 8997739
TI  - Determination of polychlorinated biphenyls and chlorinated pesticides in human
      body fluids and tissues.
AB  - A fast and reliable method for the determination of polychlorinated biphenyls
      (PCBs) and chlorinated pesticides in human body fluids and tissues is presented.
      Sample clean-up and selective enrichment of analytes are carried out by liquid
      column chromatography without a prior solvent extraction step. Analytes are
      determined either by high-resolution capillary gas chromatography with mass
      spectrometric detection, or by dual-column GC followed by electron-capture
      detection. A procedure is described for the simultaneous determination of
      environmental levels of the PCB congeners 28, 52, 101, 138, 153 and 180 in human
      cord serum. The method allows the simultaneous determination of chlorinated
      pesticides such as aldrin, DDT, DDE, BHC and HCB and is also applicable to other
      biological matrices, such as bone marrow or tissues.

PMID- 8997740
TI  - Determination of organochlorine compounds in fatty matrices. Application of rapid
      off-line normal-phase liquid chromatographic clean-up.
AB  - A clean-up method for organochlorine compounds in fatty samples based on normal
      phase liquid chromatography (NPLC) is described. To this end, an existing clean
      up procedure which uses column switching for the separation of organochlorine
      pesticides (OCPs) and polychlorinated biphenyls (PCBs) from the fat matrix was
      simplified to a single silica LC column procedure. The use of an LC column packed
      with 3 microns silica enables complete fat/OCP separation in a total fraction
      volume of 12 ml, and results in a fully automated clean-up procedure that takes
      only 32 min per sample. The method showed average recoveries of 80-110% in the
      concentration range of 1-510 micrograms/kg, with relative standard deviations of
      less than 10%. Limits of determination were in the range of 0.5-50 micrograms/kg.
      The simplified approach has shown its potential for a variety of samples, such as
      milk, pork fat, animal feed and cod liver oil, showing its general applicability
      to fatty samples.

PMID- 8997741
TI  - Selective, solid-matrix dispersion extraction of organophosphate pesticide
      residues from milk.
AB  - A rapid procedure has been developed that allows a single-step, selective
      extraction and cleanup of organophosphate (OP) pesticide residues from milk
      dispersed on solid-matrix diatomaceous material filled into disposable cartridges
      by means of light petroleum saturated with acetonitrile and ethanol. Recovery
      experiments were carried out on homogenized commercial milk (3.6% fat content)
      spiked with ethanolic solutions of 24 OP pesticides, viz., ethoprophos, diazinon,
      dimethoate, chlorpyrifos-methyl, parathion-methyl, chlorpyrifos-ethyl, malathion,
      isofenphos, quinalphos, ethion, pyrazophos, azinphosethyl, heptenophos,
      omethoate, fonofos, pirimiphos-methyl, fenitrothion, parathion, chlorfenvinphos,
      phenthoate, methidathion, triazophos, phosalone, azinphos-methyl, at levels
      ranging for the different OP pesticides from 0.02 mg/kg to 1.11 mg/kg. Average
      recoveries of four replicates were in the range 72-109% for the different OP
      pesticides, with relative standard deviations (R.S.D.) from ca. 1 to 19%, while
      dimethoate and omethoate were not recovered. Coextracted fatty material amounted
      to an average of about 4.0 mg/ml of milk. The extraction procedure requires about
      30 min. The main advantages are that extraction and cleanup are carried out in a
      single step, emulsions do not occur, several samples can be run in parallel by a
      single operator, reusable glassware is not needed and simple operations are
      required.

PMID- 8997742
TI  - Determination of the fungicide vinclozolin in honey and bee larvae by solid-phase
      and solvent extraction with gas chromatography and electron-capture and mass
      spectrometric detection.
AB  - Methods for the determination of residual vinclozolin in honey and bee larvae are
      proposed. The fungicide can be extracted with an n-hexane-acetone (70:30, v/v)
      mixture, or by passage through ODS cartridges which requires no subsequent clean
      up. Vinclozolin is quantified by capillary gas chromatography with electron
      capture and mass spectrometric detection. Recoveries from spiked samples exceed
      90%, with a relative standard deviation of 3.5-4.5%.

PMID- 8997744
TI  - On-line solid-phase extraction coupled to supercritical fluid chromatography to
      determine phenol and nitrophenols in water.
AB  - Determining of phenol and nitrophenols using solid-phase extraction on-line
      coupled to supercritical fluid chromatography (SFC) is studied. SFC quickly
      separated the compounds studied, in less than 6 min, and solid-phase extraction
      was used to decrease the limits of detection. C18, PLRP-S and a highly cross
      linked styrene-divinylbenzene copolymer in a 10 x 3 mm I.D. laboratory-packed
      precolumn were tested comparatively as sorbents in the preconcentration step.
      Tetrabutylammonium bromide was used as ion-pair reagent in the extraction process
      to increase breakthrough volumes, mainly for phenol. Performance of the method
      was checked with tap and river waters.

PMID- 8997743
TI  - Indirect photometric detection of inorganic anions in microcolumn ion
      chromatography using octadecylsilica immobilized with bovine serum albumin as
      stationary phase.
AB  - Octadecylsilica immobilized with bovine serum albumin was capable of separating
      inorganic anions. The stationary phase retained anions under acidic conditions,
      and the use of aqueous solution containing sodium iodide and tartaric acid as the
      eluent allowed the indirect photometric determination of chloride and nitrate in
      water and serum samples. The mobile phase conditions were optimized.

PMID- 8997745
TI  - Cell lipids of the Candida lipolytica yeast grown on methanol.
AB  - Candida lipolytica yeast, grown on 1% methanol as the only carbon and energy
      source, synthesized 4.9% of dry cell mass as lipids, 52.3% of which were polar
      lipids. Polar lipids consisted mainly of phospholipids and sphingolipids as their
      minor components. The total long-chain bases content has been found to account
      only for 0.7% of the polar lipids. The long-chain bases composition determined by
      thin-layer and gas chromatography shows a preponderance of trihydroxy bases and a
      small amount of dihydroxy bases. The striking finding was the high content of 19
      phytosphingosine (90.8% of total long-chain bases). Fatty acid (FA) composition
      of polar lipids was characterized by the relatively high concentration of
      unsaturated fatty acids (66.4% of total FA) and by the predominance of fatty
      acids with 16 carbon atoms (85.0% of total FA).

PMID- 8997746
TI  - Enhanced temporal resolution for the microdialysis monitoring of catecholamines
      and excitatory amino acids using capillary electrophoresis with laser-induced
      fluorescence detection. Analytical developments and in vitro validations.
AB  - This paper reports the development of a method based on capillary electrophoresis
      with laser-induced fluorescence detection for the simultaneous determination of
      catecholamines and excitatory amino acids on submicroliter microdialysis samples,
      with short analysis times (3 min or less), high sensitivity (nanomolar range,
      i.e., attomoles detected) and high separation efficiency (up to 1.10(6)
      theoretical plates). A continuous flow derivatization of small volumes of
      microdialysate (500 nl) using naphthalene-2,3-dicarboxaldehyde as derivatizing
      reagent is described. Thereafter, two subsequent off-line analyses are performed
      on each of the 30-s dialysates to determine catecholamines and amino acids. The
      performances of the present method are demonstrated in vitro by monitoring rapid
      fluctuations in the concentration of catecholamines and amino acids in the
      external microdialysis medium.

PMID- 8997747
TI  - Separation of naphthalene and flavone derivatives by micellar electrokinetic
      chromatography with double- and triple-chain surfactants.
AB  - Three surfactants, p-bis(2-dodecyloxymethyl-3-oxa-6-sodiosulfonatohexyloxy)benz
      ene (BDSB) having two sulfonate groups and two lipophilic chains, disodium 10
      dodecanoyl-5,15-bis(dodecyloxymethyl)-10-aza-4,7,13,16-tetra oxa-1,19
      nonadecanedisulfonate (DDBTN) having two sulfonate groups and three lipophilic
      chains and disodium 4,11-bis(dodecyloxymethyl)-3,6,9,12-tetraoxa-1,14-tetrade
      canedionate (DBTT) having two carboxylate groups and two lipophilic chains, were
      used in micellar electrokinetic chromatography (MEKC). Eight naphthalene
      derivatives were baseline separated at 10 mM BDSB or 5 mM DBTT, and five flavone
      derivatives at 5 mM BDSB, DDBTN or DBTT. The elution order of the naphthalene
      derivatives in MEKC with BDSB was identical with that with DDBTN. However, this
      elution order was different from that found with DBTT. In the case of the flavone
      derivatives, BDSB, DDBTN and DBTT produced the identical elution order. These
      double- and triple-chain surfactants exhibited different selectivity when
      compared with widely used sodium dodecyl sulfate.

PMID- 8997748
TI  - Applying hollow fibres for separating free and bound label in continuous-flow
      immunochemical detection.
AB  - On-line liquid chromatography-immunochemical detection (LC-ICD) provides the
      possibility to individually monitor cross-reactive compounds overcoming the need
      of tedious fraction collection. ICD is performed as a post-column reaction
      detection system and is based on a two-step immunoreaction. In the first step
      unlabelled antibodies are added to the LC effluent and allowed to react with
      antigens (analytes) eluting from the LC column. The amount of analytes bound to
      the antibodies is measured by adding, in a second step, labelled antigen to the
      reaction mixture. For quantitation, free and bound label need to be separated
      prior to detection. The present paper describes a hollow fibre module (HFM),
      which can be used for this purpose. Separation of free and bound label occurs on
      discrimination by size. Using biotin as a model compound, a detection limit of 30
      nmol/l can be reached employing anti-biotin antibodies and a low-molecular-mass
      fluorescence label in the LC-ICD system. Additional to low-molecular-mass labels,
      the HFM allows the use of small enzyme labels. In this context, horseradish
      peroxidase-labelled biotin was used as a label in combination with antibodies in
      the immunochemical detection of biotin. This allows future implementation of
      commercially available enzyme immunoassay kits in continuous-flow immunochemical
      detection.

PMID- 8997749
TI  - Development of a manganese dioxide solid-phase reactor for oxidation of toxins
      associated with paralytic shellfish poisoning.
AB  - Using manganese dioxide as a solid-phase oxidant, a post-column HPLC reactor for
      paralytic shellfish poison toxins was constructed and evaluated. Operating
      parameters such as reaction temperature and pH, flow-rate, reactor column size,
      and MnO2 particle size were studied. Based on a 3:1 signal-to-noise ratio the
      limits of detection for the non-hydroxylated toxins were in the sub-nanogram
      range, while the hydroxylated toxins were ten times less detectable. The limit of
      detection for saxitoxin was about 0.1 ng per injection. The repeatability of
      replicate injections was < or = 10% (relative standard deviation). The system was
      used to analyze extracts of shellfish and plankton yielding results that were in
      agreement with those obtained by established analytical methods. Extracts of
      shellfish contaminated at the regulatory limit of 0.8 microgram/g were
      successfully analyzed.

PMID- 8997750
TI  - Determination of phenoxy acid herbicides in vegetation, utilising high-resolution
      gel permeation chromatographic clean-up and methylation with
      trimethylsilyldiazomethane prior to gas chromatographic analysis with mass
      selective detection.
AB  - A method for the determination of phenoxy acid herbicides in vegetation samples
      is described. Macerated samples are extracted with acetone and following
      filtration and acidification, the herbicides are partitioned into
      dichloromethane. The herbicides are then cleaned-up using high-resolution gel
      permeation chromatography before undergoing rapid and efficient methylation using
      trimethylsilyldiazomethane. The resultant methyl esters are then selectively and
      sensitively analyzed by gas chromatography with mass selective detection.
      Silanized glassware was used throughout. The method has been applied to grass
      samples spiked with four phenoxy acid herbicides; 2,4-D, dichlorprop, MCPA and
      mecoprop. Recoveries around 100% and reproducibilities of 5% (n = 4) were
      achieved at two spiking levels, approximately 700 and approximately 140
      micrograms/kg.

PMID- 8997751
TI  - Migration behavior and separation of sulfonamides in capillary zone
      electrophoresis. I. Influence of buffer pH and electrolyte modifier.
AB  - The influence of buffer pH and electrolyte modifier on the migration behavior and
      separation of thirteen sulfonamides was investigated by capillary zone
      electrophoresis. The results indicate that precise optimization of buffer pH is
      crucial in improving the separation of some closely migrating sulfonamides. On
      the addition of either an appropriate amount of an organic modifier (methanol or
      acetonitrile) or a low concentration of beta-cyclodextrin (beta-CD, 0.5 mM) to a
      phosphate-borate buffer at pH 6.85 and an applied voltage of 20 kV, the
      resolution of peaks between sulfathiazole and sulfamethoxypyridarine is markedly
      enhanced and effective separations of thirteen sulfonamides are achieved within a
      relatively short time. Methanol gives better resolution than acetonitrile as an
      organic modifier. Weak inclusion complexation occurs between beta-CD and
      sulfonamides, with the exception of sulfathiazole. The formation constants of
      thirteen sulfonamides with beta-CD are reported.

PMID- 8997752
TI  - Determination of single-stranded oligodeoxynucleotides by capillary gel
      electrophoresis with laser induced fluorescence and on column derivatization.
AB  - OliGreen reagent, a new dye for complexing of oligonucleotides of low molecular
      mass was successfully utilized for their quantitative analysis using on column
      derivatization and capillary gel electrophoresis with laser induced fluorescence.
      Method optimization for the precise, accurate and reproducible quantitation of
      low-molecular-mass oligonucleotides from aqueous matrices is described.

PMID- 8997754
TI  - Lessons from the discovery of leptin: is obesity an endocrine disease?

PMID- 8997753
TI  - Enantiomer separation on a Chirasil-Dex-polymer-coated stationary phase by
      conventional and micro-packed high-performance liquid chromatography.
AB  - Polymer-coating of Chirasil-Dex (a polysiloxane-anchored permethyl-beta
      cyclodextrin) on Nucleosil 300-5 followed by thermal immobilization furnishes a
      chiral stationary phase for enantiomer separation under reversed-phase conditions
      by conventional and micro-packed HPLC.

PMID- 8997755
TI  - In vitro susceptibilities of 176 clinical isolates of Streptococcus pneumoniae to
      11 beta-lactams, erythromycin, and tetracycline.
AB  - One hundred seventy six consecutive, non-duplicate pneumococcal isolates from
      clinical specimens collected from November 1994 through February 1995 in nine
      general hospitals throughout Belgium were tested for their in vitro
      susceptibilities to penicillin, ampicillin, amoxycillin with and without
      clavulanate, cefaclor, cefuroxime, cefonicid, cefprozil, cefpodoxime, cefotaxime,
      imipenem, tetracycline, and erythromycin by means of the NCCLS microdilution
      test. The overall rate of decreased susceptibility to penicillin was 12.5%,
      including 6.3% of intermediately and 6.3% of fully resistant isolates.
      Penicillin, ampicillin amoxycillin, amoxycillin/clavulanate, cefuroxime,
      cefotaxime and imipenem had the highest activity on a weight basis (MIC50 < or =
      0.008 microgram/ml), followed by cefpodoxime and erythromycin (MIC50 of 0.015
      microgram/ml), cefprozil and tetracycline (MIC50 of 0.12 microgram/ml), and
      eventually, cefaclor and cefonicid (MIC50 of 0.5 microgram/ml). Aggregate rates
      of susceptible plus intermediately resistant isolates at NCCLS-recommended
      breakpoints, i.e. overall percentages of isolates likely to respond to increased
      antibiotic doses in vivo (except for meningitis), were 100.0% for imipenem and
      cefotaxime, 98.9% for amoxycillin with and without clavulanate, 93.8% for
      penicillin, and 90.9% for cefuroxime. Overall rates of susceptibility to
      erythromycin and tetracycline amounted to 78.4% and 72.7%, respectively. MIC
      values of all beta-lactams increased with those of penicillin. Ampicillin was
      equally active as penicillin against isolates with reduced susceptibility to the
      latter (MIC90 of 2 micrograms/ml); imipenem, cefotaxime, and amoxycillin with and
      without clavulanate however, were more active (MIC90 3, 1, and 1 doubling
      dilution, respectively, below that of penicillin), while cefpodoxime, cefuroxime,
      cefprozil, cefonicid, and cefaclor on the other hand, were less active (MIC90, 1,
      1, 2, 5, and 5 doubling dilutions, respectively, above that of penicillin). In
      conclusion, the present data confirm that pneumococcal resistance to penicillin
      has increased in Belgium, suggest that resistance to erythromycin may have
      stabilised, and reveal an unexpectedly high rate of resistance to tetracycline.
      Imipenem was the most active antibiotic tested overall, and amoxycillin with or
      without clavulanate the most active oral antibiotic, with activity almost similar
      to that of cefotaxime.

PMID- 8997757
TI  - Epidural abscess: case report and review of the literature.
AB  - Spinal epidural abscess is an uncommon site of infection, resulting in back pain,
      fever, weakness and loss of sensibility. These signs should suggest the
      diagnosis, and quick confirmation by MRI should be performed. Immediate surgical
      decompression and antibiotherapy is necessary, because this is the base of a
      possible successful functional recovery. Empiric therapy consisting of high dose
      of penicillinase-resistant antibiotics is advised because most often an epidural
      abscess is caused by Staphylococcus aureus. However, because other bacteria can
      be involved, an aminoglycoside or a cephalosporin should be added to the empiric
      treatment, until the results of the cultures are known. When diagnosis and
      therapy are delayed, permanent paralysis and death are common.

PMID- 8997756
TI  - Splenic infarction: report of three cases of atherosclerotic embolization
      originating in the aorta and retrospective study of 64 cases.
AB  - The authors report 3 cases of thromboembolic splenic infarction due to
      atherosclerosis of the thoracic aorta and the splenic artery. On this occasion, a
      retrospective analysis of 64 splenic infarcts showed that, in contrast to the
      literature, the leading aetiology in our series consisted of haematologic
      disorders (50%), followed by cardiovascular diseases (29%) and by digestive
      disorders (20%). Mean age was 58 +/- 17 years and 50% of the patients were aged
      below 60 years. Hospital mortality rate was high (34%) but not directly related
      to splenic infarction, suggesting that splenic infarction often occurs in the
      setting of severe underlying diseases. Splenic infarct is part of the
      differential diagnosis of the left upper quadrant pain and can also mimic renal
      disorders. Laboratory values may show an inflammatory syndrome and an increase in
      serum lactate deshydrogenase. Diagnosis is often made by CT scan and can be
      confirmed by a selective spleen scintigraphy. Transoesophageal echocardiography
      is essential in the detection of cardiac and thoracic aorta embolic material.

PMID- 8997758
TI  - Inside Addiction: peering into the editorial review process.

PMID- 8997759
TI  - Fatal heroin 'overdose': a review.
AB  - The current paper examines critically the literature on deaths attributed to
      heroin overdose, and examines the characteristics and circumstances of such
      deaths. In particular, the dominance of the widely held belief that heroin
      related fatalities are a consequence of overdose is challenged. Deaths attributed
      to overdose represented in the literature are typically older, heroin-dependent
      males not in drug treatment at the time of death. Fatalities involving only
      heroin appear to form a minority of overdose occasions, the presence of other
      drugs (primarily central nervous system depressants such as alcohol and
      benzodiazepines) being commonly detected at autopsy. Furthermore, deaths
      attributed to overdose are likely to have morphine levels no higher than those
      who survive, or heroin users who die from other causes. It is concluded that the
      term overdose is, in many cases, a misleading term, since it implies the same
      mechanism of death in all cases, an implication that is neither clinically useful
      nor consistent with published data. Implications for the prevention of heroin
      related deaths are discussed.

PMID- 8997760
TI  - The effectiveness of inpatient and outpatient treatment for alcohol abuse: the
      need to focus on mediators and moderators of setting effects.
AB  - Previous reviews have concluded that there was no evidence for the superiority of
      inpatient over outpatient treatment of alcohol abuse, although particular types
      of patients might be more effectively treated in inpatient settings. In this
      review, we first consider the conceptual rationales that have been offered to
      support inpatient and outpatient treatment. Following that, the results of the
      relevant research on setting effects are presented. Five studies had significant
      setting effects favoring inpatient treatment, two studies found day hospital to
      be significantly more effective than inpatient treatment, and seven studies
      yielded no significant differences on drinking-related outcome variables. In all
      but one instance in which a significant effect emerged, patients in the
      'superior' setting received more intensive treatment and patients were not
      'preselected' for their willingness to accept random assignment to treatment in
      either setting. Studies finding significant setting effects also conducted more
      treatment contrasts (18.6 vs. 4.9), on average, and had a mean statistical power
      level of 0.71 (median 0.79) to detect a medium-sized effect, whereas studies with
      no significant findings had an average power level of 0.55 (median 0.57). When
      inpatient treatment was found to be more effective, outpatients did not receive a
      respite in the form of inpatient detoxification and the studies were slightly
      less likely to have social stability inclusion criteria and to use random
      assignment to treatment settings. We consider the implications of our findings
      for future research, especially the need to examine the conceptual rationales put
      forward by proponents of inpatient and outpatient treatment, i.e. mediators and
      moderators of setting effects.

PMID- 8997761
TI  - The future of smoking cessation therapy in the United States.
AB  - Six trends that are likely to influence the future content, format, delivery and
      reach of smoking cessation therapy in the United States are discussed: (1)
      changing characteristics of smokers (e.g. more likely to be poor, have
      psychiatric co-morbidity and be more nicotine dependent), (2) health care reform
      demands for cost-effectiveness, (3) development of guidelines/algorithms that
      recommend stepped-care approaches, (4) continued emphasis on smoking as a form of
      drug dependence requiring intensive pharmacological and behavior therapy for some
      smokers, (5) interest in harm-reduction strategies for smokers unable or
      unwilling to quit (and 6) smoking cessation therapies become reimbursable on par
      with other drug dependencies.

PMID- 8997763
TI  - The disadvantage of being advantaged?--on a social gradient in excess mortality
      among alcohol abusers.
AB  - Do alcohol abusers from upper social classes have a more elevated excess
      mortality than alcohol abusers from lower social classes? This question was
      empirically assessed by analyses on data from a 40-year prospective study of more
      than 40,000 Norwegian conscripts on whom data on social class (i.e. educational
      level), alcohol abuse (admission to treatment) and cause specific mortality
      before the age of 60 years were available. The results demonstrated a social
      gradient in excess mortality: relative risk of premature death was 2.7 among
      those with the lowest educational level (primary school only) increasing to 6.2
      among those with the highest educational level at conscription (grammar school).
      Among the alcohol abusers the risk of premature death, was slightly, but not
      significantly higher among those highly educated as compared to those with less
      education. Thus, alcohol abuse was not only found to elevate the individual's
      risk of premature death, but it also appeared to outweigh the advantages of those
      more socially privileged with respect to health and mortality. The question as to
      whether social class differences in selection to treatment could account for the
      observed social gradient in excess mortality is focused in the discussion.

PMID- 8997764
TI  - Gender differences in the risk of alcohol dependence: United States, 1992.
AB  - Data from a representative sample of US adults revealed that 24% of male life
      time drinkers and 15% of female life-time drinkers met the DSM-IV criteria for
      life-time alcohol dependence, i.e. dependence during the year preceding interview
      or in any 12-month period prior to that year. The median interval from first
      drink to onset of dependence was 3.6 years for men and 3.0 years for women. After
      using survival techniques to adjust for potential gender differences in the
      exposure to risk of developing alcohol dependence, the cumulative conditional
      probability of having experienced onset of dependence was 35.1% for men and 24.6%
      for women. The conditional probability of onset of dependence was equal for men
      and women in the first year after initiation of drinking, about 30% higher for
      men in the period 1-4 years after the first drink, and about 45% higher for men
      thereafter. After using proportional hazards models to adjust for the effects of
      age cohort, race and ethnicity, family history of alcoholism and age at first
      drink, these period-specific risk ratios remained virtually unchanged. Including
      a measure of average daily ethanol intake during periods of heaviest consumption
      rendered most of the gender differences statistically insignificant, revealing a
      slight excess risk of female dependence within the first year after initiation of
      drinking among the heaviest drinkers and leaving an excess male risk of
      dependence mostly among individuals with average daily intakes of less than one
      ounce of ethanol. The results suggest that different frequencies of binge
      drinking might help to account for these remaining gender differences and that
      men's and women's relative risks of developing alcohol dependence may vary as a
      function of life cycle stage, with men's excess risk greatest in the
      college/young adult years.

PMID- 8997765
TI  - Predicting underage drinking and driving behaviors.
AB  - A social-psychological model of underage drinking and driving (DUI) and riding
      with drinking drivers (RWDD) was tested with data from a random digit dial
      telephone survey of 706 16-20-year-old drivers from seven western states in the
      United States. Consistent with the model, a structural equations analysis
      indicated that DUI and RWDD were primarily predicted by (a) expectancies
      regarding the physical risks of DUI, (b) normative beliefs about the extent to
      which friends would disapprove of DUI, (c) control beliefs about the ease or
      difficulty of avoiding DUI and RWDD and (d) drinking. Expectancies concerning
      enforcement had a significant effect on RWDD, but not on DUI. Among the
      background and environmental variables included in the analysis, only night-time
      driving and age had significant direct effects on DUI and RWDD. Drinking and
      involvement in risky driving had indirect effects on DUI and RWDD that were
      mediated through expectancies and normative beliefs. Males, European Americans,
      Latinos, respondents who drove more frequently and respondents who were less
      educated held beliefs that were more favorable toward DUI and RWDD, drank more
      and engaged more frequently in risky driving. As a result, such individuals may
      be at greater risk for DUI and RWDD.

PMID- 8997766
TI  - Heroin addiction in Bahrain: 15 years experience.
AB  - This study describes the development and outcome of a new treatment programme for
      the management of heroin addiction in Bahrain. The problem reached its peak in
      the early 1980s with several reported deaths and with the involvement of many
      disciplines in the overall response. In 1983, treatment of all addicts was
      restricted by law to the government psychiatric hospital. The newly established
      specialized drug unit was overwhelmed by the number of patients seeking
      treatment. The lack of sufficient resources and suitably trained staff forced the
      unit to adopt an outpatient maintenance therapy approach for most of its clients.
      In 1987, a new comprehensive treatment programme was introduced that relies on a
      clear philosophy, safe detoxification (using objective scales for withdrawal
      manifestations) rather than maintenance therapy, followed by psychological and
      social rehabilitation. A national committee for drug addiction was formed and an
      intensive programme of education was started at all levels. The results indicate
      an initial increase at inpatient level but a marked drop of outpatient
      attendance. The use of the Opioid Objective Withdrawal Manifestations Scale
      (OOWMS) revealed that only a small number of our patients developed moderate or
      severe signs of withdrawal that required detoxification, and the rate of
      dispensed controlled medication was reduced by 99%. The effect of this approach
      is discussed, with special reference to the need for a collaborative effort from
      all disciplines in planning, implementing, continuously evaluating and modifying
      the national programmes for handling the serious problem of addiction.

PMID- 8997767
TI  - The New Zealand Rugby Injury and Performance Project: alcohol use patterns within
      a cohort of rugby players.
AB  - Although heavy drinking has traditionally been associated with rugby, the
      drinking patterns of New Zealand rugby players have not been examined. Three
      hundred and forty-eight rugby players (257 males and 91 females), completed the
      Alcohol Use Disorders Identification Test (AUDIT) at the beginning of the 1993
      rugby season. The mean AUDIT scores were 11.2 (SD = 5.1) for the males and 8.7
      (4.1) for the females: a cut-off of 8.0 has been recommended by the developers of
      the instrument for identifying alcohol use disorders. The consumption of large
      quantities of alcohol, and a high frequency of heavy drinking sessions were the
      norm for this group. Sixty-one per cent of males and 38% of females consumed six
      or more drinks in a session at least weekly: typically, men drank 10 or more
      drinks in a session and women 5-6 drinks. The patterns of drinking exhibited by
      the cohort give cause for concern regarding the health risks associated with such
      behaviour.

PMID- 8997769
TI  - Alcohol advertising in France.

PMID- 8997768
TI  - The drinks industry dilemma.

PMID- 8997770
TI  - Liquorspeak and the developing world.

PMID- 8997771
TI  - The drinks industry and alcohol research.

PMID- 8997772
TI  - Political and economic influences on alcohol-related science: some
      considerations.

PMID- 8997773
TI  - "Good guys" versus "bad guys" in scientific inquiry.

PMID- 8997774
TI  - A personal note from a retiring president.

PMID- 8997775
TI  - How does one write satire in Rome? A reply from the editors.

PMID- 8997776
TI  - Perspectives on precipitants of relapse.

PMID- 8997777
TI  - Conceptualizations of relapse: a summary of psychological and psychobiological
      models.
AB  - While substance use disorders have long been recognized as chronic relapsing
      conditions, it has mainly been in the last two decades that clinical researchers
      have been systematically attending to the nature and processes of relapse. These
      efforts have led to the development of a variety of psychological and
      psychobiological models of relapse. These models are summarized in the present
      article, with particular attention placed on each model's basic principles and on
      the precipitants of relapse predicted by the respective models. The delineation
      of these models may help facilitate subsequent cross-referencing and cross
      fertilization of thinking in this important area.

PMID- 8997778
TI  - What is a relapse? Fifty ways to leave the wagon.
AB  - Binary thinking has often guided research and practice in the addiction field.
      For example, emphasis has been given to identifying whether an individual is
      "alcoholic" or not, and the dichotomous judgement that a client is either
      drinking or abstinent has been used to judge treatment effectiveness. Research on
      the nature of alcohol problems, however, indicates that they lie along several
      modestly interrelated continuous dimensions of severity, rather than occurring as
      a single syndrome qualitatively distinct from normality. Similarly, changes in
      addictive behaviors in general, and treatment outcomes in particular, are complex
      phenomena not readily captured by dichotomous classification. The term "relapse"
      is itself seriously problematic in various ways, and its definition elusive. It
      represents a somewhat arbitrary binary judgement imposed on the flow of behavior,
      and carries negative evaluative overtones. A potentially detrimental abstinence
      violation effect is implicit in the very use of the term "relapse", which thereby
      may become a self-fulfilling prophecy. Further, it implicitly pathologizes what
      is in fact a rather common event in the course of behavior change, and embodies
      an unrealistic and inaccurate conception of how successful change occurs over
      time. For these reasons, it may be useful in research and clinical practice to
      abandon the notion of "relapse" and focus instead on terminology that better
      describes the normal resolution process for addictive behaviors.

PMID- 8997779
TI  - Assessment issues and domains in the prediction of relapse.
AB  - The present paper provides a brief overview of methodological issues involved in
      the process of assessment related to the classification and prediction of
      relapse. These include conceptual and operational definitions of relapse,
      retrospective versus prospective assessment, attributional biases in recalling
      relapse events, single versus multiple determinants of relapse, static versus
      dynamic assessment models, and the necessary level of specificity involved in the
      assessment of relapse categories. Additionally, general domains representing
      distal personal characteristics, intermediate background variables and factors
      proximal in time to relapse situations are reviewed. Potential variables
      appropriate for assessment within each of these domains are described. It is
      concluded that relapse is best understood as a complex process having multiple
      and interactive determinants that vary in their temporal proximity from and their
      relative influence on relapse. An adequate assessment model must be sufficiently
      comprehensive to include theoretically relevant variables from each of the
      multiple domains and different levels of potential predictors.

PMID- 8997780
TI  - Taxonomy of high-risk situations for alcohol relapse: evolution and development
      of a cognitive-behavioral model.
AB  - The purpose of this paper is to provide an historical overview of the development
      of the taxonomy of high-risk situations for relapse in patients receiving
      abstinence-based treatment for alcoholism. Research conducted during the 1970s on
      determinants of relapse is briefly reviewed, beginning with a preliminary
      analysis of relapse patterns in alcoholics treated with aversion therapy.
      Theoretical foundations underlying the development of the taxonomy are then
      discussed with an emphasis on social-learning theory and its implications for
      cognitive-behavioral interventions for relapse prevention. Findings supporting
      the efficacy of coping-skills training for high-risk relapse situations, based on
      a prospective treatment outcome study for inpatient alcoholics, are also
      presented in support of the clinical validity of the relapse model. The paper
      concludes with a description of the refined and extended taxonomy of high-risk
      situations and the associated cognitive-behavioral model of relapse described in
      the Marlatt & Gordon (1985) text on relapse prevention.

PMID- 8997782
TI  - The reliability of Marlatt's taxonomy for classifying relapses.
AB  - Marlatt's focus on the relapse situation has had a major impact upon research and
      clinical practice in treating addictions. One component of his work was the
      development of a taxonomy for classifying precipitants of relapse. This taxonomy
      has been incorporated into the nomenclature of clinicians and clinical
      researchers as part of an explanatory framework for understanding relapses.
      Despite the taxonomy's influence it has never been examined for the reliability
      of its use across research studies. The present study compared the reliability of
      independent classifications of 149 relapse episodes by trained raters at three
      research laboratories. Despite considerable across-laboratory training,
      reliability was found to be inconsistent for research purposes. It is concluded
      that comparability of results based on Marlatt's relapse taxonomy across
      independent studies must be subject to question, and assumptions necessary for
      the aggregation of a knowledge base are not supported. Recommendations are
      offered for improving the reliability of the taxonomy and the methods used to
      collect taxonomy data. More generally, questions regarding the value of the
      specific relapse categories, as well as the overall taxonomy, are raised.

PMID- 8997781
TI  - Replication and extension of Marlatt's taxonomy of relapse precipitants: overview
      of procedures and results. The Relapse Research Group.
AB  - The Relapse Replication and Extension Project (RREP) was a multisite study to
      replicate and extend Marlatt's taxonomy of relapse precipitants. In addition to
      replicating Marlatt's original taxonomic system, three independent research teams
      utilized prospective designs to identify additional predictors of relapse and
      developed and evaluated two alternative systems for assessing high risk relapse
      situations. This overview describes the replication methodology, summarizes seven
      RREP studies completed by the three research groups, and discusses five cross
      cutting conclusions emerging from the studies. These conclusions are: (1)
      reliability of Marlatt's taxonomic system was variable both within and across the
      three research sites; (2) Marlatt's taxonomic system showed little predictive
      validity in analyses that used pretreatment relapse data to predict post
      treatment relapse, but there are important unresolved issues; (3) an alternative
      taxonomy provided little more predictive validity than the original taxonomy even
      though it measured more dimensions of relapse situations and provided greater
      analytic flexibility; (4) the Reasons for Drinking Questionnaire appeared to be a
      successful psychometric transformation of Marlatt's taxonomy, one which did
      demonstrate predictive validity; and (5) Marlatt's taxonomy was based on a time
      intensive model of relapse prediction whereas RREP prospective analyses
      represented time-extensive models of relapse prediction. Coping responses are
      noted to be effective predictors of relapse under both models.

PMID- 8997783
TI  - Construct validation analyses on the Marlatt typology of relapse precipitants.
AB  - Marlatt's typology of relapse precipitants has had a major influence on clinical
      research and practice in the substance use disorders. The purpose of this study
      was to evaluate the construct validity of the typology, which was done in several
      ways. First, precipitants of the relapse coded at the baseline assessment and for
      the first drink post-treatment admission were compared. In addition, baseline
      relapse precipitants were compared with the highest factor scores recorded in the
      baseline Inventory of Drinking Situations data. A third set of analyses concerned
      the relationship among Marlatt precipitant codes, psychiatric diagnoses, and
      Alcohol Dependence Scale scores. The subjects were 142 men and women who were
      recruited for this study upon their admission to inpatient or outpatient alcohol
      treatment programs. Participants completed a baseline assessment covering
      substance use, including information on the precipitants of a pretreatment
      "relapse", and other areas of functioning. Subjects then completed bimonthly
      follow-up assessments during the course of 1 year. The results showed support for
      only one of the predictions regarding the construct validity of the Marlatt
      typology. Possible explanations for these findings and their implications for
      clinical research and practice are discussed.

PMID- 8997784
TI  - Predictive validity of Marlatt's relapse taxonomy versus a more general relapse
      code.
AB  - Marlatt's system for classifying relapses involves integrating information about
      the context of a relapse into a judgment about the most critical aspects of the
      situation. Constraints in this taxonomy, however, may limit its validity. On a
      sample of 300 subjects drawn from six treatment facilities, we compared the
      predictive validity of Marlatt's taxonomy with that of a coding scheme with fewer
      constraints. Marlatt's taxonomy does not significantly predict drinking outcome,
      nor does it predict time to relapse. There is weak evidence, however, that under
      some circumstances Marlatt's taxonomy can predict the type of relapse
      subsequently observed. The alternative coding system also does not seem useful
      for predicting drinking outcome, although a possible association was found
      between internal attribution and time to return to heavy drinking. The
      alternative system does seem to be able to detect repetitive aspects of
      subsequent relapse situations; lack of social interactions, family setting,
      anxiety and depression were most likely to repeat. It may be useful to consider
      these relapse attributes in treatment planning. The minimal predictive validity
      for both the Marlatt and the alternative relapse code may be due to weaknesses in
      the relatively unstructured interview used to gather the data, or to failure to
      assess the most critical dimensions relating to subsequent relapse.

PMID- 8997785
TI  - Gender differences in relapse situations.
AB  - Gender differences in variables relating to alcohol treatment are receiving
      increased attention. Most reports indicate gender differences in both
      intrapersonal, interpersonal and environmental trans-situational variables that
      relate specifically to women's drinking. This study investigates gender
      differences in the immediate relapse situation itself. These differences are then
      examined in the context of trans-situational (i.e. across time) affective and
      cognitive variables and social support. This report is part of a larger study
      designed to replicate Marlatt's taxonomy of high risk situations for relapse, and
      to examine alternative methods of describing relapse situations. Three hundred
      subjects (169 men, 131 women) were recruited from six different inpatient and
      outpatient programs. Subjects were asked to identify their last relapse before
      entering the index treatment. Details of the drinking episode itself were also
      obtained, e.g. number of drinking days in episode, drinking to intoxication,
      presence of others. Measures of state and trait affect, expectancies, and social
      support were also collected. There were no gender differences in Marlatt's
      taxonomy, or in drinking topography during relapse. At baseline, women reported
      drinking less, and drinking less often than men. However, women drank to
      intoxication more often than men. Surprisingly, men relapsed alone more often
      than did women. Men and women report relapsing frequently with same sex friends,
      and women showed a tendency to relapse in the presence of romantic partners. Men
      also tend to report more positive mood states during relapse than women, which is
      congruent with the finding that women report more depression. Severity of
      drinking pattern was found to be an important confounding variable in these
      analyses. It is suggested that gender differences found in individuals in
      treatment for alcohol problems may reflect societal differences between men and
      women, and that taking these differences into account in designing treatment
      programs may improve outcomes.

PMID- 8997787
TI  - Marlatt's classification of relapse precipitants: is the Emperor still wearing
      clothes?
AB  - The present paper provides comments on the series of papers dealing with the
      reliability and validity of Marlatt's taxonomy of relapse precipitants. The
      results of these papers suggest that the degree of reliability and predictive
      validity of the original relapse taxonomy, as operationalized and employed in the
      present studies, is lower than would be hoped for. Both methodological factors in
      the studies and limitations in the taxonomy are discussed. While the original
      taxonomic system has provided a useful heuristic model and a guide for clinical
      intervention, it is recommended that it be modified to improve its utility in
      research and practice. A number of specific recommendations are provided for
      modifying the system.

PMID- 8997786
TI  - Relapse research and the Reasons for Drinking Questionnaire: a factor analysis of
      Marlatt's relapse taxonomy.
AB  - A factor analysis (n = 183) of Marlatt's relapse taxonomy as assessed by the
      Reasons for Drinking Questionnaire (RFDQ) (see Appendix I, this article) was
      conducted using a heterogeneous alcohol treatment sample. Results indicated that
      the predominant factor was negative emotions. The second factor consisted of
      social pressure and positive emotions, and a third factor consisted of physical
      withdrawal, wanting to get high, testing control, substance cues and urges to
      drink. Each of the 13 categories in the Marlatt taxonomy loaded on one of the
      three factors. Scores on the first factor for the first and second lapses were
      correlated. The same held true for the other two factors. The negative emotions
      factor was positively related to blood alcohol level on the first day of the
      lapse, the lapse duration (in days), and occurrence of a second lapse (even when
      controlling for alcohol dependence). The negative emotions factor in turn was
      related to client reports of alcohol dependence, trait anger, and depression (all
      positively). Women scored higher on the first factor, and men scored higher on
      the second factor. The third factor was inversely related to the number of days
      of abstinence preceding the lapse. Taken together, these analyses, illustrate
      that different precipitants occur together, suggesting that clients might
      productively be trained in the use of specific relevant coping skills to address
      potential relapse precipitants. Focusing on the third RFDQ factor may be
      particularly important in the early stages of abstinence. The importance of anger
      and depression management during alcohol treatment is also highlighted by these
      results.

PMID- 8997788
TI  - Is Marlatt's relapse taxonomy reliable or valid?
AB  - The Relapse Replication and Extension Project (RREP) has failed to provide
      empirical support for Marlatt's relapse taxonomy. Neither the reliability of the
      original Marlatt coding system nor its predictive or construct validity was
      supported by this group of studies. The present commentary explores a number of
      possible reasons for the generally negative outcomes. These findings should
      certainly lead to a re-evaluation of Marlatt's relapse taxonomy and its
      operationalization. Nevertheless, despite the negative results, there are a
      number of reasons why the general Relapse Prevention concept is likely to survive
      in some form: it has been widely adopted and imitated clinically, key elements of
      the taxonomy are often focal points of treatment, and clinical research studies
      have repeatedly supported some elements of the taxonomy (e.g. negative emotional
      states, social pressure, interpersonal conflict, positive emotional states and
      temptations/urges). The RREP also evaluated some modifications of the original
      taxonomy as well as the use of more structured assessment instruments, and some
      of these provided more promising results. Further developments will need to take
      into account both research needs for greater precision, most likely through the
      use of more structured assessment instruments, and clinical needs for richness of
      detail and sensitivity to a wide variety of life circumstances.

PMID- 8997789
TI  - Lest taxonomy become taxidermy: a comment on the relapse replication and
      extension project.
AB  - In this commentary on the Relapse Replication and Extension Project, several
      points are addressed. First, the selection of the pretreatment "baseline relapse"
      as the key predictor variable for post-treatment relapse in the predictive and
      construct validity studies is questioned. It is doubtful whether retrospective
      accounts of drinking episodes after 4 days of abstinence qualify as relapse
      episodes for the following reasons: clients may not have been committed to
      abstinence (e.g. weekend binge drinkers); treatment may have included coping
      skill training for pretreatment high-risk situations (i.e. treatment intervention
      is viewed as a "nuisance variable"). By assuming that a client's retrospective
      report of a poorly defined pretreatment "relapse" is predictive of the type of
      relapse episode experienced during the post-treatment follow-up assessment is to
      commit an error of "taxidermy" in evaluating the reliability and validity of the
      taxonomy; i.e. the tendency for researchers to "stuff and permanently mount"
      distal baseline episodes as static predictor variables, thereby depriving them of
      their dynamic and fluid role as proximal determinants in the relapse process. The
      difference between researchers who assess distal trait predictors of relapse and
      clinicians who focus more on proximal state predictors in conducting relapse
      prevention therapy is discussed and illustrated by means of a case study.
      Finally, the metaphor of relapse as "falling off the wagon" is described as an
      example of a systems approach to relapse prevention.

PMID- 8997790
TI  - What predicts relapse? Prospective testing of antecedent models.
AB  - Predictors of relapse to drinking were examined in a clinical sample of 122
      individuals seeking outpatient treatment for alcohol problems. Drinking status
      and a variety of predictor variables were measured every two months for one year
      following presentation for treatment. In addition to pretreatment
      characteristics, potential antecedents of relapse were assessed at each point
      within five domains: (1) the occurrence of negative life events; (2) cognitive
      appraisal variables including self-efficacy, alcohol expectancies, and motivation
      for change; (3) client coping resources; (4) craving experiences; and (5)
      affective/mood status. Although the occurrence of adverse life events did not
      predict 6-month relapse, all other domains singly accounted for significant
      variance in drinking outcomes. Proximal antecedents (from the prior 2-month
      interval) significantly and substantially improved predictive power over that
      achieved from pretreatment characteristics alone. When analyzed jointly, these
      predictors accounted for a majority of variance in 6-month relapse status. A
      prospective test supported Marlatt's developmental model of relapse, pointing to
      two client factors as optimally predictive of resumed drinking: lack of coping
      skills and belief in the disease model of alcoholism.

PMID- 8997791
TI  - Understanding relapse in the broader context of post-treatment functioning.
AB  - There exists much interest in developing more sophisticated conceptual and data
      analytic frameworks for evaluating and understanding the post-treatment
      functioning of alcoholics. Much of this interest has been fostered by the
      systematic research endeavors of Moos and his colleagues, whose "systems model"
      of treatment outcome closely parallels multivariate models of illness and health.
      This article focuses on an extrapolation of the systems model to the study of
      relapse, viewing relapse as one outcome of a set of independent variables that
      include person and environmental factors. The subjects were 142 clients entering
      either inpatient or outpatient treatment for alcoholism. Preliminary assessments,
      using path analyses and multiple regression models, are presented on the
      interrelationships between background characteristics, pretreatment alcohol
      involvement/ symptomatology, treatment, coping skills/responses, stressors and
      relapse/outcome following treatment entry. The results overall showed a
      considerable amount of convergence in the sense that the composite "blocks"
      representing background characteristics, alcohol involvement/symptomatology and
      coping skills/responses generally were significant predictors of various relapse
      and other posttreatment functioning variables. However, the variables
      contributing to the predictive power of a particular composite varied as a
      function of the dependent variable being assessed. The conceptual model and
      associated analytic strategies guiding this research would appear to hold much
      potential for advancing knowledge in this area.

PMID- 8997792
TI  - Looking forward and back to relapse: implications for research and practice.
AB  - In this commentary, the three principal investigators of the Relapse Replication
      and Extension Project (RREP) reflect on clinical and research implications of
      study findings from the three collaborating sites. A primary purpose of RREP was
      to study the reliability and validity of a taxonomy of relapse antecedents
      originally proposed by Marlatt two decades ago. Under the best of research
      conditions, with extensive training and practice, it was difficult to achieve
      reliability of coding with the original three-level system, although with only
      two levels of classification more reasonable albeit variable reliability was
      found. Modifications may improve the taxonomy's reliability, but RREP data
      indicate that a more appropriate strategy is to measure possible antecedents of
      relapse by continuous scales such as those provided by Annis, Heather and Litman.
      There is reasonably consistent evidence for two common antecedents of relapse:
      negative emotional states, and positive emotional states in a social context.
      Antecedents of relapse show only modest consistency within individuals from one
      occasion to the next. The causes to which clients attribute relapses may exert a
      significant effect on future drinking episodes. Stable and internal attributions,
      such as are commonly associated with a dispositional disease model, may serve to
      perpetuate relapse. From the RREP studies, the availability of coping skills
      appears to be a potent protective factor, and ineffective coping a consistent
      predictor of relapse. Implications for clinical research and practice are
      considered.

PMID- 8997793
TI  - Latent transition analysis for longitudinal data.
AB  - Assessing outcome is a critical problem for the study of addictive behaviors.
      Traditional approaches often lack power and sensitivity. Latent Transition
      Analysis is an alternative procedure that is applicable to categorical latent
      variable models such as stage models. The method involves four different types of
      parameters, each of which may be relevant to different research questions. Two
      examples that employ the Stages of Change construct are used to illustrate the
      method. In the first example, three different models of longitudinal change are
      compared. In the second example, the effects of an expert system intervention for
      smoking is compared to a control condition. The method permits the investigation
      of a series of specific comparisons: (1) the effectiveness of the intervention
      for individuals in different stages can be assessed; (2) the effectiveness of the
      intervention can be evaluated for different time intervals; and (3) the effects
      of intervention on both progression through the stages and regression through the
      stages or relapse can be assessed. Other potential applications of the method are
      also discussed.

PMID- 8997794
TI  - Application of random-effects regression models in relapse research.
AB  - This article describes and illustrates use of random-effects regression models
      (RRM) in relapse research. RRM are useful in longitudinal analysis of relapse
      data since they allow for the presence of missing data, time-varying or invariant
      covariates, and subjects measured at different timepoints. Thus, RRM can deal
      with "unbalanced" longitudinal relapse data, where a sample of subjects are not
      all measured at each and every timepoint. Also, recent work has extended RRM to
      handle dichotomous and ordinal outcomes, which are common in relapse research.
      Two examples are presented from a smoking cessation study to illustrate analysis
      using RRM. The first illustrates use of a random-effects ordinal logistic
      regression model, examining longitudinal changes in smoking status, treating
      status as an ordinal outcome. The second example focuses on changes in motivation
      scores prior to and following a first relapse to smoking. This latter example
      illustrates how RRM can be used to examine predictors and consequences of
      relapse, where relapse can occur at any study timepoint.

PMID- 8997795
TI  - Work and health: of isolation, sisyphus, and barbarian beds.

PMID- 8997797
TI  - Cautions against buying into illusion of control.

PMID- 8997796
TI  - Discusses the need for studies on alternatives to ERT and HRT therapy.

PMID- 8997798
TI  - Traditional Chinese materia medica (TCMM).

PMID- 8997799
TI  - Centers provide OAM with 'deliverables'.

PMID- 8997800
TI  - A review of reimbursement policies for alternative and complementary therapies.

PMID- 8997801
TI  - The Columbia-Presbyterian Complementary Care Center: comprehensive care of the
      mind, body, and spirit.

PMID- 8997802
TI  - Systematic clinical auditing in complementary medicine: rationale, concept, and a
      pilot study.
AB  - A scientific evaluation of complementary medical practices commonly used in
      healthcare is urgently required. Although randomized clinical trials are the
      primary tool for such an evaluation, for a number of conceptual and pragmatic
      reasons, they should not be the only tool. The authors propose systematic
      clinical auditing as a concept to (1) provide information on the "epidemiology"
      of complementary medical practices, (2) make the processes used in the daily
      practice of these complementary methods clearly intelligible, and (3) give a
      preliminary estimation of outcomes. Systematic clinical auditing uses mainly
      observational studies of large samples of patients. A pilot study was conducted
      to investigate the feasibility of using a systematic clinical audit in a hospital
      for traditional Chinese medicine in Germany. All 1597 patients admitted between
      February 1, 1992, and August 31, 1993, were included in the study. Patients'
      characteristics, diagnoses, and preventive and therapeutic interventions were
      recorded, and patients were asked to rate the intensity of their main complaints
      (on scale of 1 to 10) at admission; at discharge; and at 2, 6, and 12 months
      after admission. About two thirds of all patients had chronic pain complaints;
      the most common diagnosis was migraine (n = 244). Nearly all patients received
      acupuncture and Chinese herbal therapy; 61% received tuina massages, and 16%
      received qigong. The mean intensity of main complaints was 7.0 (2.0, SD) at
      admission, 4.6 (2.4) at discharge, and 5.5 (2.7) 12 months after admission. In
      the authors' opinion, systematic clinical auditing is a valuable tool for
      collecting basic information on structural characteristics, processes, and
      outcomes in complementary medicine and for determining representative and
      relevant questions for future randomized clinical trials.

PMID- 8997803
TI  - Entrainment and the cranial rhythmic impulse.
AB  - Entrainment is the integration or harmonization of oscillators. All organisms
      pulsate with myriad electrical and mechanical rhythms. Many of these rhythms
      emanate from synchronized pulsating cells (eg, pacemaker cells, cortical
      neurons). The cranial rhythmic impulse is an oscillation recognized by many
      bodywork practitioners, but the functional origin of this impulse remains
      uncertain. We propose that the cranial rhythmic impulse is the palpable
      perception of entrainment, a harmonic frequency that incorporates the rhythms of
      multiple biological oscillators. It is derived primarily from signals between the
      sympathetic and parasympathetic nervous systems. Entrainment also arises between
      organisms. The harmonizing of coupled oscillators into a single, dominant
      frequency is called frequency-selective entrainment. We propose that this
      phenomenon is the modus operandi of practitioners who use the cranial rhythmic
      impulse in craniosacral treatment. Dominant entrainment is enhanced by
      "centering," a technique practiced by many healers, for example, practitioners of
      Chinese, Tibetan, and Ayurvedic medicine. We explore the connections between
      centering, the cranial rhythmic impulse, and craniosacral treatment.

PMID- 8997804
TI  - Homeopathic treatment of depression and anxiety.
AB  - BACKGROUND: Homeopathy is a well-established therapeutic system with potential
      relevance to psychiatry, but as yet it is largely untested. OBJECTIVE: To report
      the use of homeopathic treatment in patients with depression and anxiety.
      METHODS: Individually selected homeopathic remedies were used on an outpatient
      basis to treat 12 adults who had major depression, social phobia, or panic
      disorder. The patients either requested homeopathic treatment or received it on a
      physician's recommendation after partial or poor response to conventional
      therapies. Duration of treatment was 7 to 80 weeks. Response was monitored by
      using a clinical global scale (n = 12), the self-rated SCL-90 scale (n = 8), and
      the Brief Social Phobia Scale (n = 4). RESULTS: Overall response rates were 58%
      according to the clinical global improvement scale and 50% according to the SCL
      90 or the Brief Social Phobia Scale. CONCLUSIONS: Homeopathy may be useful in the
      treatment of affective and anxiety disorders in patients with mildly to severely
      symptomatic conditions.

PMID- 8997805
TI  - Voluntary control of vascular tone by using skin-temperature biofeedback
      relaxation in patients with advanced heart failure.
AB  - BACKGROUND: Advanced heart failure is characterized by activation of the
      sympathetic nervous system and intense vasoconstriction. Biofeedback-relaxation
      techniques have been used successfully to treat conditions with similar
      pathophysiological features. OBJECTIVES: The purpose of this study was to
      determine if conscious control of skin temperature via a biofeedback-relaxation
      technique could produce vasodilation and alter central hemodynamic status and
      circulating levels of catecholamines in patients with heart failure. METHODS:
      Forty patients with advanced heart failure were randomly assigned to either an
      intervention or a control group. The study was done in a special cardiac step
      down unit accepting patients for hemodynamic monitoring. The patients in the
      intervention group had one session of skin-temperature biofeedback augmented by
      imagery of hand warmth and modified progressive muscle relaxation. Skin
      temperature, systemic vascular resistance, cardiac output, plasma levels of
      norepinephrine and epinephrine, oxygen consumption, respiratory rate, and
      pulmonary wedge pressure were measured before and after the biofeedback session.
      Control patients had the same measurements made but were not given instruction in
      biofeedback-relaxation techniques. RESULTS: Patients in the biofeedback
      relaxation and control groups had comparable clinical profiles at baseline.
      Patients undergoing biofeedback-relaxation showed the following changes: (1)
      increase in skin temperature of 3.1 +/- 2.8 degrees F (1.7 +/- 1.5 degrees C) in
      the finger and 1.5 +/- 5.2 degrees F (0.4 +/- 1.2 degrees C) in the foot, (2)
      increase in cardiac output of 0.30 +/- 0.33 L/min, (3) decrease in systemic
      vascular resistance of 152 +/- 225 dyne.sec.cm-5, and (4) decrease in respiratory
      rate of 4.5 +/- 3.2 breaths per minute. The biofeedback group exhibited no
      changes in catecholamine levels or oxygen consumption. No changes in any of these
      parameters were seen in the control group. DISCUSSION: Despite the presence of
      marked vasoconstriction in patients with advanced heart failure, a single session
      of biofeedback-relaxation can increase finger temperature and cardiac output and
      decrease systemic vascular resistance and respiratory rate, apparently without
      effect on systemic levels of catecholamines or oxygen consumption.

PMID- 8997806
TI  - Spiritual healing and folklore research: evaluating the hypnosis/placebo theory.

PMID- 8997807
TI  - Jim Jealous, DO. Healing and the natural world. Interview by Bonnie Horrigan.

PMID- 8997808
TI  - Thyroid gland as sentinel: interface between internal and external environment.

PMID- 8997809
TI  - A review of complementary medicine in Europe.

PMID- 8997810
TI  - Our research approaches must meet the goal of improving patient care.

PMID- 8997811
TI  - Sleep and rheumatic disease.
AB  - Patients with rheumatic diseases often exhibit sleep disturbance. Identification
      of primary sleep disorders; medical, neurologic, and psychologic illnesses;
      circadian factors; and the use and effect of medications, drugs, and alcohol will
      provide a strong basis for pursuing both pharmacologic and nonpharmacologic
      intervention. Recent clinical research confirms the frequent comorbidity of sleep
      disturbance, pain, fatigue, stress, and mood disturbance in patients with
      rheumatic disease. It is essential for effective management to recognize these
      "symptom syndromes" that are often responsive to treatment (suggesting a common
      biologic action and effect of the drugs used) despite a continuing presence of
      underlying chronic disease. The pathophysiologic relationships of these comorbid
      symptoms are mostly unknown, so this is an area for further study.

PMID- 8997813
TI  - Influenza in Canada--1995-1996 season.

PMID- 8997812
TI  - Another look at minocycline.

PMID- 8997814
TI  - Enterohemorrhagic Escherichia coli infection--Japan.

PMID- 8997815
TI  - Childhood pertussis immunization status as reported by parents and the
      completeness of public-health and physician records in Nova Scotia.

PMID- 8997816
TI  - Association between measles infection and the occurrence of chronic inflammatory
      bowel disease.

PMID- 8997817
TI  - Serostatus surveillance testing of HIV-I infection among Zimbabwean psychiatric
      inpatients, in Zimbabwe.
AB  - OBJECTIVE: To investigate seroprevalence rates of HIV infection among Zimbabwean
      psychiatric inpatients. DESIGN: An identity-unlinked procedure, for ELISA and
      Western blot HIV testing of consecutively admitted psychiatric patients, was used
      during the four month period of the study. The seropositive groups were further
      categorized along the WHO case definition of HIV/AIDS infection criteria. The
      blood results were coded and linked to various demographic variables and risk
      factors. All data were measured at either nominal or ordinal levels. Comparisons
      between variables were made by chi-square test for proportion and independence.
      SETTING: Harare Central Hospital Psychiatric Unit, Harare, Zimbabwe. SUBJECTS: A
      total of 143 inpatients (60.8 pc males and 39.2 pc females), mean(SD) age 32.5
      (10.5) years and the mean(SD) duration of psychiatric illness of 4.21 (1.7)
      years. MAIN OUTCOME MEASURE: Prevalence of HIV/AIDS infection among psychiatric
      patients. RESULTS: The seroprevalence rate of HIV infection was 23.8pc and was
      significantly related to high education attainment (p < 0.03) and unemployment
      status of the patients (p < 0.03). CONCLUSION: There is an urgent need to develop
      and apply preventive interventions for HIV infected psychiatric patients.

PMID- 8997818
TI  - Antibiograms and plasmids of Staphylococcus aureus and coagulase negative
      staphylococci isolated from different clinical sources.
AB  - OBJECTIVES: To ascertain the antibiotic resistance patterns and plasmids of
      Staphyl coccus aureus and coagulae negative staphylococci isolated from different
      clinical specimens in Lagos, Nigeria. DESIGN: Prospective study involving the
      screening of specimens of blood, urine, skin and soft tissue infections, vagina,
      urethra, eye, ear, nose, pleural fluid and seminal fluid obtained from patients
      attending the Lagos University Teaching Hospital (LUTH) and Providence Hospital
      Diagnostic Laboratories, Lagos, Nigeria. SETTING: A laboratory based study
      conducted in the Microbiology Unit, University of Lagos and the National
      Institute for Medical Research (NIMR) Lagos, Nigeria. The patients were from
      different communities in Lagos. SUBJECTS: A total of 200 patients that were
      positive for the presence of S. aureus and coagulase negative staphylococci
      (CONS) were employed in the study. MAIN OUTCOME MEASURES: Frequency of isolation
      of S. aureus and coagulase negative staphylococci (CONS) from the different
      clinical specimens determination of their resistance profile using standard
      techniques for the isolation of both organisms and the Kirby-Bauer disc diffusion
      method for antibiotic testing. RESULTS: All the S. aureus and CONS isolates were
      sensitive to novobiocin and ofloxacin. Ninety eight (80 pc) of S. aureus isolates
      were resistant to tetracycline (Tet), 73 (60 pc) to Streptomycin (Str), and 49
      (40 pc) to Chloramphenicol (Chl). All the S. aureus isolates were resistant to
      Penicillin (P) and only two (2 pc) and four (three pc) were resistant to
      Cefuroxime (Cxm) and Ceftriasone (Cro) in that order. Twenty six (21 pc) of S.
      aureus isolates were resistant to Methicillin. For CONS, 92 pc were resistant to
      Penicillin, 47 (60 pc) to streptomycin and 40 (51 pc) to tetracycline. Nineteen
      (24 pc) were resistant to Methicillin. Further antibiotic sensitivity results
      revealed the following patterns: 87 (71 pc) and 29 (36 pc) of S. aureus and CONS
      respectively showed P RTet"R, pattern of resistance. The resistance pattern
      PREryRGmRCazRCxmR was shown by only one (17 pc) of S. aureus and none (Opc) of
      CONS. Only 59% and four pc of S. aureus and CONS isolates showed resistance
      pattern ChlREryR, CazR respectively. Results of plasmid profiles showed that 48
      (96 pc) of 50 S. aureus and 26 (87 pc) of 30 CONS isolates harboured one or more
      plasmids of molecular sizes ranging from 1.0 Kb to 19.5 Kb. Nine (19 pc) of 48 S.
      aureus and three (12 pc) of CONS isolates showed plasmid identity. CONCLUSION: We
      assert that although isolates of S. aureus and CONS showed multiple antibiotic
      resistance which could be plasmid mediated, only about five pc of both organisms
      showed resistance pattern ChlREryRCazRTetRCxmRSxtRGmR and EryRGmRCazRCxmR and
      this is of chemotherapeutic importance. Both organisms, were highly sensitive to
      Ceftriazone, Ceforoxime and Gentamicin. The high levels of resistance of many
      antibiotics may be attributable to indiscriminate use or antibiotic abuse in the
      community.

PMID- 8997819
TI  - Endomyocardial fibrosis in Zimbabwe--how rare is it? A report of two cases.
AB  - In Africa endomyocardial fibrosis (EMF) is rare outside countries where it is
      endemic, such as Uganda, Mozambique and Ivory Coast. The only published case in
      Zimbabwe was in 1957. We describe two female patients aged 22 and 19 years who
      presented within seven months of each other with typical clinical,
      electrocardiographic and echocardiogaphic features of right ventricular EMF. We
      would like to suggest that EMF exists in Zimbabwe and needs to be considered in
      the differential diagnosis of patients presenting with suggestive clinical
      features.

PMID- 8997820
TI  - Malaria infection of the cord and birthweights in Nigerians.
AB  - OBJECTIVES: To establish the prevalence of cord malaria parasitaemia in Nigerians
      and to elucidate its effect on birthweight. DESIGN: Case series. SUBJECTS: 1,905
      women resident in three parts of Nigeria. SETTING: University of Jos Teaching
      Hospital, Jos, Plateau State, Bauchi Specialist Hospital and Eku Baptist
      Hospital, Eku Delta State. RESULTS: 21.6 pc (405) were infected with Plasmodium
      falciparum. The prevalences by residence were 21.8 pc in Bauchi, 23.2 pc in Jos
      and 17.5 pc in Eku. The cord malaria prevalence was significantly higher among
      newborns of first pregnancies than those of two or more pregnancies. Although no
      significant seasonal fluctuation in mean birthweights was found, the mean for the
      August to October quarter were the lowest in the three study sites. The mean
      birthweights of newborns with parasitized cords were generally lower than those
      that were not parasitized. Birthweights of infected cords also decreased with
      increasing parasite densities. Of the newborns 215 (11.2 pc) weighed < or = 500
      g, of which 202 (10.5 pc) had cord malaria. CONCLUSION: There is a need for more
      efficient malaria chemoprophylaxis regime during antenatal care in public
      hospitals to effectively manage malaria in pregnancy and reduce the incidence of
      low birthweight.

PMID- 8997821
TI  - The use of the Rectus abdominis muscle to suspend the bladder in the treatment of
      uretero-vaginal fistulae.
AB  - This study evaluates a new and simpler technique for suspending the bladder
      during uretero-neocystostomy, using the posterior surface of the Rectus abdominis
      muscle rather than an vesico-psoas hitch. The technique was employed in six
      consecutive patients who presented with ureteric injuries following hysterectomy
      or caesarean section. Each patient was fully evaluated preoperatively, and the
      results of surgery evaluated after three months in five out of six women. All the
      patients were Zulu women who had sustained injuries to the lower five centimetres
      of a ureter at hysterectomy or caesarean section. This study was conducted in the
      obstetric and gynaecological unit of Eshowe Hospital, a 460 bed sub-regional
      hospital in northern KwaZulu Natal. The technique described in this paper proved
      to be easy to perform. Every patient was continent following surgery. All those
      who returned for follow up had normal drainage of the affected ureter. We
      conclude that this is a useful alternative to vesico-psoas hitch for suspending
      the bladder during uretero-neocystostomy.

PMID- 8997822
TI  - Thrombocytopenia in human immune deficiency virus infection. Literature review,
      case report and future directions.

PMID- 8997823
TI  - The lymphomas.
AB  - Hodgkin's disease and the malignant lymphomas are, by all available evidence,
      eminently curable neoplasms. The debates, therefore, on how best the largest
      numbers of individuals in any community can receive appropriate treatment and
      this implies their ready access to an experienced multi disciplinary combined
      clinic. It is important that proper perspective be retained in the African
      context so that preventive medicine can be employed where appropriate but, based
      on current understanding, those with lymphoreticular malignancy become immediate
      beneficiaries of whatever diagnostic and therapeutic resources need to be
      expended in ensuring optimal outcome. The last word is far from written on how
      we, as inhabitants of the African continent, will achieve this goal and so
      measure up to our obligation. However, as resources continue to contract, three
      observations justify reiteration. Firstly, diagnostic skills need to be honed by
      experienced pathologists together reviewing all biopsy material and, wherever
      possible, participating in national or international study groups. Secondly, the
      silly distinction propagated by some self serving individuals who fantasize that
      state hospitals and private clinics somehow differ, must be replaced by a more
      responsible attitude in which resources are pooled in the common quest for
      maintaining academic standards. Thirdly, given acceptance of the above common
      sense proposals, a mechanism will exist for the establishment and constant
      upgrading of national guidelines for management on agreed and achievable
      protocols. Whilst the theme remains that of tested conventional treatment,
      flexibility must exist, where appropriate, for palliative care on the one hand
      with scientific growth and exploration of innovative options on the other. One
      might conclude by observing that Africa is most certainly unique and this extends
      to the frequency with which some of these tumours occur; a classical example
      would be Burkitt's Lymphoma. This places an obligation on all of us to gather and
      record such experiences and, from this basis, sustain our intellectual drive by
      forging international bonds with colleagues in the First World. Such
      collaboration will provide the natural bridge between clinical studies in Africa
      and the more sophisticated cellular and molecular biology that is being provided
      by basic scientists in other parts of the world. Such a marriage is practical and
      both parties stand to gain significantly in the research, development and
      evaluation of new drugs and protocols that, ultimately, serve the best interests
      of patients and do so on a world-wide basis.

PMID- 8997825
TI  - A proposal for the reporting of p-values in hypothesis testing and evaluation.

PMID- 8997824
TI  - The function of arachnoid villi/granulations revisited.
AB  - OBJECTIVE: To establish the current viewpoint with regards to the role of
      arachnoid villi/granulations in cerebrospinal fluid (CSF) absorption. DESIGN:
      Retrospective study. SUBJECTS: Journal articles published between 1913 and 1993.
      MAIN OUTCOME MEASURE: The contribution of arachnoid villi/granulations to CSF
      absorption from the subarachnoid space. RESULTS: From available literature, it is
      yet to be proved that arachnoid villi/granulations are the major sites for CSF
      absorption from the subarachnoid space into the venous system. They may, however,
      play an important role in the absorption of CSF's waste products of neuronal
      metabolism (mainly CSF proteins) under normal physiological conditions.
      Furthermore, it would appear that, under pathological conditions, the absorption
      of CSF proteins can take place at other CSF absorption sites. CONCLUSION: The
      paucity of data on the relationship between the development of arachnoid villi,
      the superior sagittal sinus, the superficial cortical vessels and the
      subarachnoid space warrants that an ontogenic study be conducted in order to
      achieve a better understanding of the function of arachnoid villi which is
      currently speculative.

PMID- 8997826
TI  - Dysphagia following anterior cervical spine surgery.
AB  - Although previous reports have identified dysphagia as a potential complication
      of anterior cervical spine surgery (ACSS), current understanding of the nature
      and etiologies of ACSS-related dysphagia remains limited. The present study was
      undertaken to describe the patterns of dysphagia that may occur following ACSS.
      Thirteen patients who exhibited new-onset dysphagia following ACSS were studied
      retrospectively by means of chart review and videofluoroscopic swallow study
      analysis. Results indicated that a variety of swallowing impairments occurred
      following ACSS. In 2 patients, prevertebral soft tissue swelling near the
      surgical site, deficient posterior pharyngeal wall movement, and impaired upper
      esophageal sphincter opening were the most salient videofluoroscopic findings. In
      another 5 patients, the pharyngeal phase of swallowing was absent or very weak,
      with resulting aspiration in 3 cases. In contrast, an additional 4 patients
      exhibited deficits primarily of the oral preparatory and oral stages of
      swallowing including deficient bolus formation and reduced tongue propulsive
      action. Finally, 2 patients exhibited impaired oral preparatory and oral phases,
      a weak pharyngeal swallow, as well as prevertebral swelling. Thus, a variety of
      swallowing deficits, due possibly to neurological and/or soft tissue injuries,
      may occur following ACSS.

PMID- 8997827
TI  - Pharyngo-esophageal dysphagia in Parkinson's disease.
AB  - The radiologic characteristics of pharyngoesophageal (PE) dysfunction in
      Parkinson's disease (PD) are not well established, partly because most previous
      studies have examined only small numbers of patients. We administered a dynamic
      videofluoroscopic swallowing function study to 71 patients with idiopathic PD.
      Using the Hoehn and Yahr disease severity scale, patients were subdivided into
      those with mild/moderate disease, subgroup I (n = 38), and advanced PD disease,
      subgroup II (n = 33). From pharyngeal ingestion to gastric emptying, bolus
      transport was normal in only 2 patients. The most common abnormalities occurring
      during pharyngeal ingestion included impaired motility, vallecular and pyriform
      sinus stasis, supraglottic and glottic aspiration, and deficient epiglottic
      positioning and range of motion. Esophageal abnormalities were multiple but most
      commonly included delayed transport, stasis, bolus redirection, and tertiary
      contractions. Typical aberrations of lower esophageal sphincter (LES) function
      included an open or delayed opening of the LES and gastro-esophageal reflux. A
      pathogenesis linking PE with the pathology of PD is proposed.

PMID- 8997829
TI  - Videofluoroscopic evaluation of aspiration with visual examination of the gag
      reflex and velar movement.
AB  - The purpose of the present study was to investigate the relationship between
      prevalence of aspiration as determined by videofluoroscopic evaluation and
      prevalence of the gag reflex and velar movement as determined by direct visual
      examination. One hundred adult patients underwent a videofluoroscopic evaluation
      of aspiration with either an esophagram (n = 31), upper gastrointestinal series
      (n = 18), small bowel series (n = 23), or modified barium swallow procedure (n =
      28), and concomitant evaluation of the gag reflex and velar movement on
      phonation. All studies were performed using the lateral, upright position, and
      all patients drank at least 5 cc of single contrast barium. Aspiration was
      defined as penetration of material below the level of the true vocal folds. A
      normal gag reflex and normal velar movement on phonation were observed in 14 of
      15 (93%) patients who exhibited objective documentation of aspiration with
      videofluoroscopy. Conversely, 19 of 20 (95%) patients without a gag reflex were
      observed with videofluoroscopy to be without aspiration. Normal velar movement on
      phonation was observed in 99 of 100 (99%) patients. There was no significant age
      difference between patients with or without a gag reflex. No relationship was
      found between the prevalence of aspiration and the gag reflex or velar movement
      on phonation. It was concluded that the presence of a gag reflex does not protect
      against aspiration, and the absence of a gag reflex does not predict aspiration.

PMID- 8997830
TI  - Comparative review of techniques for recording respiratory events at rest and
      during deglutition.
AB  - The coordination between swallowing and respiration is essential for safe
      feeding, and noninvasive feeding-respiratory instrumentation has been used in
      feeding and dysphagia assessment. Sometimes there are differences of
      interpretation of the data produced by the various respiratory monitoring
      techniques, some of which may be inappropriate for observing the rapid
      respiratory events associated with deglutition. Following a review of each of the
      main techniques employed for recording resting, pre-feeding, feeding, and post
      feeding respiration on different subject groups (infants, children, and adults),
      a critical comparison of the methods is illustrated by simultaneous recordings
      from various respiratory transducers. As a result, a minimal combination of
      instruments is recommended which can provide the necessary respiratory
      information for routine feeding assessments in a clinical environment.

PMID- 8997831
TI  - Vagal control of pharyngeal constrictor activity in rabbits.
AB  - The neural control mechanism of pharyngeal constrictor (PC) activity of rabbits
      was examined in relation to vagal afferents. The average firing rate of single PC
      units of unilaterally vagotomized animals increased from 0.52 to 8.83 spikes/sec
      by cooling of the intact vagus nerve at 5 degrees C. Time courses of increases in
      PC and diaphragmatic (Dia) activities were examined during the period from the
      start of vagal cooling to the time when the PC reached the maximum firing rate.
      Although Dia activity linearly increased along with the respiratory cycles, PC
      activity slowly increased during the first three-quarters of the period and
      rapidly increased during the last quarter. The result suggests that more impulses
      in the vagus nerve are required to be blocked by cooling at a lower temperature
      for eliciting an increase in PC activity compared with that in Dia activity. The
      increase in PC activity evoked by bilateral vagotomy (from 0.30 to 10.07
      spikes/sec) was not different from that by vagal cooling. The presumable afferent
      nerve fibers responsible for the increase in PC activity were discussed.

PMID- 8997832
TI  - Mealtime difficulties in a home for the aged: not just dysphagia.
AB  - A mealtime screening tool was administered to 349 residents of a home for the
      aged to determine the prevalence of mealtime difficulties including, but not
      limited to, dysphagia. Mealtime difficulties, as assessed during a single meal
      observation of each resident, were documented in 87% of these individuals. Though
      68% exhibited signs of dysphagia, 46% had poor oral intake, 35% had positioning
      problems, and 40% exhibited challenging behaviors. An increased prevalence of
      mealtime difficulties was related to both the presence and degree of cognitive
      impairment. Oral intake was best among residents with severe cognitive
      impairment, many of whom received partial to total feeding assistance. In
      contrast, poor oral intake was associated with mild-moderate cognitive
      impairment, pointing to a need for more aggressive intervention with this group.
      The results clearly demonstrate that the prevalence of a wide range of eating
      related problems far exceeds accepted estimates of dysphagia alone and support a
      multidisciplinary approach to mealtime interventions for the institutionalized
      elderly. Additionally, the magnitude of problems identified has implications for
      both resource and staff-training requirements in long-term care facilities.

PMID- 8997835
TI  - Vocal fold paralysis following the anterior approach to the cervical spine.

PMID- 8997834
TI  - A comment on "Modified barium swallow: clinical and radiographic correlation and
      relation to feeding recommendations" (Dysphaghia 11: 187-190, 1996)

PMID- 8997836
TI  - Management of vagus nerve injury after carotid endarterectomy.

PMID- 8997837
TI  - The swallowing side effects of botulinum toxin type A injection in spasmodic
      dysphonia.

PMID- 8997838
TI  - Management of psychiatric disorders in Kenya (1963-1996)

PMID- 8997839
TI  - Prevalence of psychiatric disorders in general practice in Nairobi.
AB  - This study was designed to examine the point prevalence rate of psychiatric
      disorders among adult patients at primary care attenders in Nairobi A total
      sample of 186 of the 295 consecutive patients, aged 16-75 years (mean of 32.3 +/-
      11.1) were studied within the period January 1990 and December 1993. Using a
      cross-sectional design study, they were assessed for psychiatric disorders by the
      Self Rating Questionnaire (SRQ), the Clinical Interview Schedule/revised (CIS-R),
      and the W.H.O Audit Instrument for Alcohol abuse. The final diagnosis of a
      psychiatric disorder was made according to DSM-111-R criteria. A matched gender
      analysis using Chi-squared (chi 2) test was carried out. The findings were that
      the overall prevalence rate of psychiatric disorder was 0.43% with an incidence
      of 0.43% per 1000 persons. This information can be used to provide a framework
      for the formulation of a more effective mental health policy.

PMID- 8997840
TI  - Induction of chloroquine resistance in Plasmodium yoelii nigeriensis.
AB  - Chloroquine resistance was induced in Plasmodium yoelii nigeriensis by the method
      of drug pressure. Twenty five albino mice were used at each passage and each of
      them was inoculated intra-peritoneally with approximately 10(5) erythrocytes
      infected with the parasite. The first fifteen mice divided into three groups of
      five mice each were treated with different sub-curative doses of chloroquine
      which usually cleared the infection for a few days before recrudescence. Inocula
      for passages to the next set of mice was made from the recrudesced infection. The
      sub-curative dose was progressively increased as rapidly as the build-up of
      parasitaemia permitted. The last ten mice divided into two groups of five mice
      each were used in the 'two percent test' to assess the level of resistance in the
      parasite. Full resistance to the maximum tolerated dose of chloroquine to the
      host mouse (80 mg/kg body weight) was reached at passage 20.

PMID- 8997841
TI  - Efficacy of Cymbopogon giganteus and Enantia chrantha against chloroquine
      resistant Plasmodium yoelii nigeriensis.
AB  - The antimalarial activity of boiled water extracts of two medicinal plants
      (Cymbopogon giganteus and Enantia chlorantha) against chloroquine resistant
      Plasmodium yoelii nigeriensis in albino mice was assessed. Twenty-five mice were
      used for each extract. Each mouse was inoculated with approximately 10(5)
      erythrocytes infected with chloroquine-resistant P.y. nigeriensis. At five to
      seven percent parasitaemia, the mice were randomly divided into five groups of
      five mice each. The first four groups were treated intraperitoneally for three
      consecutive days with different doses of the stock solution per mouse. The two
      extracts cleared the infection in a dose-dependent manner.

PMID- 8997842
TI  - Comparison of prognostic determinants in childhood acute lymphoblastic leukaemia
      in negroid and Caucasian populations.
AB  - The response of acute lymphoblastic leukaemia (ALL) to treatment remains very low
      in developing countries. Many factors have been cited to be probable determinants
      of prognosis. To compare the prognostic determinants of childhood ALL in
      developed Western countries and developing African countries, a review of
      published data was carried out. Both an electronic and manual search were
      undertaken. The manual search was confined to four leading African journals. All
      articles were subjected to an eligibility criteria. The proportions of six
      prognostic factors were either extracted from the original publications or
      calculated from available published data. A pooled proportion was computed and
      95% confidence intervals calculated and compared. Eleven articles fulfilled the
      inclusion criteria. One article with nineteen study subjects was available on
      black African population. Six articles from developed countries were excluded.
      The proportions of children below the age of two years or above the age of nine
      years constituted 26% (CI = 0.24,0.28) and 37% (CI = 0.15,0.59) in developed
      countries and the Black African population respectively. There was a
      statistically significant higher population of children with high total WBC count
      in African children compared to developed countries. Proportions for other
      factors in developed countries and developing countries respectively were as
      follows: T-cell immunophenotype (17% and 60%), FAB-L2, L3 (15% and 83%), CNS
      involvement (5% and 13%) and mediastinal shadows on CXR (8% and 13%). It is
      concluded that there is a need for basic epidemiologic research on childhood ALL
      in African countries. The frequency of poor prognostic determinants for ALL in
      developing African countries is higher than in developed countries.

PMID- 8997843
TI  - Chronic lymphocytic leukaemia in Ethiopians.
AB  - One hundred and two cases of chronic lymphocytic leukaemia (CLL) were seen at the
      Tikur Anbessa (Black Lion) Hospital, in Addis Ababa, Ethiopia, from January 1982
      to December 1994. The age range was 35-91 (mean 55.6 +/- 11.08) years. The male
      to female ratio was 3.6:1. The commonest symptoms were weakness, weight loss,
      fever and sweating. The commonest signs were lymphadenopathy, splenomegaly and
      hepatomegaly. Fifty six per cent had Rai stage III and IV, only three patients
      were in stage 0. Of those treated with chemotherapy, 22.0% and 48.8% achieved
      complete and partial remissions respectively. Twelve patients are still alive and
      on follow up for 2-138 (median 18) months, 69 are lost to follow up after 0-132
      (median 3) months and 21 are dead 0.5-84 (median 2.8) months after diagnosis. Of
      those that died, 13 were in stage IV and five in stage III. The main causes of
      death were septicaemia of undetermined origin in eight and pneumonia in seven.
      Thus CLL is not a rare disease in this centre. Its presentations are similar to
      cases reported in the literature. Optimal treatment is not possible due to lack
      of chemotherapeutic agents and supportive care. Therefore, we suggest that
      referral centres be equipped for better management of CLL patients.

PMID- 8997844
TI  - Childhood cancers in a referral hospital in Kenya: a review.
AB  - Following the outbreak of human immune deficiency virus (HIV) infection in the
      early 1980's, there has been an increase in reported cases of Kaposi's sarcoma,
      among other childhood malignancies, from the East and Central African region. To
      assess the status of childhood cancers at Kenyatta National Hospital during the
      AIDS epidemic period and to compare the findings with those obtained before the
      outbreak, relevant data were extracted from ward admission registers for all
      children admitted in the paediatric wards and in whom a diagnosis of a malignant
      disease was confirmed. The data were summarised in tables and bar charts. The
      hospital based prevalence for malignant diseases was 1.27% (CI = 1.23,1.31).
      Lymphoma (51.3%), leukaemia (21.3%), nephroblastoma (8.5%) and rhabdomyosarcoma
      (5.2%) are the most common childhood cancers. Compared with earlier studies, the
      frequency of acute lymphoblastic leukaemia, Hodgkin's disease and
      rhabdomyosarcoma appear to have increased. Despite the AIDS epidemic, there has
      been no obvious increase in number of cases of Kaposi's sarcoma.

PMID- 8997846
TI  - Demographic characteristics, socioeconomic profile and contraceptive behaviour in
      patients with abortion at Jimma Hospital, Ethiopia.
AB  - This is a descriptive prospective study on abortion patients admitted to Jimma
      Hospital, south west Ethiopia from September 1992 to August 1993. Forty four
      Percent (N = 285) of the patients admitted were interviewed using a
      questionnaire. Fifty three percent (N = 151) had induced while the remaining had
      spontaneous abortion. Patients with induced abortion were younger (P = 0.0000)
      and had smaller family size (P = 0.06283) than patients with spontaneous
      abortion. Induced abortion was more common among students (30.9%) and those with
      secondary education (71.8%) whereas spontaneous abortion was most common among
      housewives (64.4%). Almost 50% of the patients with induced abortion were
      married. Eighty two percent of all interviewed had unwanted pregnancies. The
      contraceptive methods most commonly used were the pill and abstinence. Fifty
      patients got pregnant while on the pill. The most common reason for not using
      contraceptives or discontinuation was the side effects associated with the pill.

PMID- 8997845
TI  - Barriers to contraceptive use in Kenya.
AB  - This study was designed to identify and to better understand the barriers to
      contraceptive use among Kenyan-couples. Data were collected through structured
      interviews and focus group discussions among couples not planning for pregnancy
      and not using any effective contraceptive method. The study was conducted in the
      Baba Dogo urban slum area of Nairobi, and Chwele, a rural sub-location in
      Bungoma, western Kenya. Some important barriers to contraceptive use were
      identified in couples wishing to space or limit further births. Those barriers
      included lack of agreement on contraceptive use and on reproductive intentions;
      husband's attitude on his role as a decision maker; perceived undesirable side
      effects, distribution and infant mortality; negative traditional practices and
      desires such as naming relatives, and preference for sons as security in old age.
      There were also gaps in knowledge on contraceptive methods, fears, rumours and
      misconceptions about specific methods and unavailability or poor quality of
      services in the areas studied. This paper recommends that information and
      educational programmes should be instituted to increase contraceptive knowledge,
      to emphasise the value of quality of life over traditional reproductive practices
      and desires, and to improve availability and quality of services.

PMID- 8997847
TI  - Attitudes to prenatal testing and notification for HIV infection in Nairobi,
      Kenya.
AB  - Four hundred antenatal clinic attendants were surveyed for their attitude to
      testing and notification for HIV infection test results. The participants were
      systematically sampled from the antenatal clinic at the Kenyatta National
      Hospital, Nairobi, and interviewed using a closed-ended structured questionnaire.
      All the attendants had heard of HIV, and only 5(1.3%) did not know how Acquired
      Immunodeficiency Syndrome (AIDS) presents. Fifty one percent of them had no
      objection to their blood being tested for HIV. In fact, 52.5% thought, wrongly,
      that blood was routinely tested for HIV at the hospital's antenatal clinic. More
      than one third (35.8%) of respondents wished their permission to be obtained
      before the testing and 95% wished to be informed of the test result.
      Acceptability of testing was 33.8%, for Named Voluntary Testing, 62.0% for
      Universal Testing and 1.0% for Anonymous Testing. All the women said they would
      want to use a method of contraception, principally tubal ligation, if found HIV
      seropositive and 63.7% would seek a termination of pregnancy. In this study
      population, acceptability and expressed willingness to know HIV test results and
      willingness to let a spouse/sexual partner know the result was high. This paper
      makes recommendations that HIV testing be made available at the ANC, together
      with competent pre and post-test counselling.

PMID- 8997848
TI  - Immunohaematological findings in healthy and HIV-1 infected adults in Dar es
      Salaam, Tanzania.
AB  - In order to assess the prognostic value of lymphocyte subsets and immune
      activation markers in HIV-1 infected Tanzanian patients, peripheral white blood
      cell(WBC) count, total lymphocytes, CD4+ and CD8+ T-lymphocytes and Beta-2
      microglobulin (B-2M) concentrations were determined among healthy HIV-1
      seronegative Tanzanian blood donors and in infected Tanzania individuals in
      different clinical stages of HIV-1 infection. CD4+ T-lymphocytes, CD8+ T
      lymphocyte percentages, CD4:CD8 lymphocyte ratios and the concentrations of B-2M
      were strongly correlated with the clinical stages of HIV-1 infection. These
      results suggest that B-2M could be a useful prognostic marker in HIV-1 infection
      in settings where T-lymphocyte subset determinations cannot be done.

PMID- 8997849
TI  - High frequency of sexually transmitted diseases among pregnant women in Dar es
      Salaam, Tanzania: need for intervention.
AB  - In order to determine the prevalence and characteristics of sexually transmitted
      diseases (STDs) in pregnant women (PW) attending a primary health care antenatal
      clinic (ANC) in metropolitan Dar es Salaam, Tanzania, a randomly selected sample
      of PW in their second or third trimesters were invited to participate at their
      first visit. They were interviewed using a questionnaire and underwent genital
      examination. Genital swabs were obtained for microscopy and/or culture isolation
      of Candida albicans, Trichomonas vaginalis, and Neisseria gonorrhoeae. Blood
      specimens were also obtained for serological testing for syphilis and for
      antibodies to the human immunodeficiency virus (HIV). A total of 777 PW aged 14
      to 40 years were seen. Parities ranged from 0 to 10. Prevalence of syphilis,
      trichomoniasis, gonorrhoea and HIV infection were 4.0%, 22.7%, 3.6% and 15.2%,
      respectively. At least one acute STD (excluding HIV infection) was found in 32.8%
      of the PW. The prevalence of multiple STDs (excluding HIV infection) was higher
      in teenagers (45.3%, 77/170) than in PW in other age groups (29.2%, 177/607) (p <
      0.001). The prevalence of HIV infection in teenage PW was 10.0%. Most STDs were
      least prevalent in PW who were married monogamously. Of the 732 PW who had one or
      more genital infections (including infection with Candida species), 669 (91.4%)
      had one or more genital complaints. However, most of the genital complaints were
      not disease specific. Since this study has shown that the prevalences of acute
      STDs were high in PW, especially in teenagers, it is recommended that all PW in
      Tanzania should be screened for STDs syndromically including the use of
      appropriate clinical and laboratory examination whenever possible.

PMID- 8997850
TI  - Steady-state anticonvulsant drug levels in epileptic patients.
AB  - Steady state concentrations of three anticonvulsant drugs (phenobarbitone,
      phenytoin and carbamazepine) were measured in plasma samples from fifteen
      patients (eight males and seven females; ages: 13-49 years; body weights: 44-70
      kg), attending the outpatient Neurology Clinic at Kenyatta National Hospital. In
      addition, total protein and albumin levels were measured in plasma from patients
      taking phenytoin. Total protein levels were normal (range: 6.3-7.6 g/dl) in all
      patients except in one patient (10.7 g/dl). Albumin levels were also normal
      (range: 3.7-4.1 g/dl) in all patients except one (25.4 g/dl). One patient on
      phenobarbitone and three patients on phenytoin had no detectable drug levels in
      their plasma. In the remainder, phenobarbitone, phenytoin and carbamazepine
      steady state concentrations were 8.7-21.1 mg/L (N = 8), 9.3-27.3 mg/L (N = 6) and
      10-19.7 mg/L (N = 5), respectively. The unbound fraction of phenytoin in plasma
      (fu) was normal(approximately 0.1) in six patients, but relatively high (0.2) in
      one patient. Most patients in the study complied with the prescribed treatment
      and their epilepsy was controlled. Cases where drug levels were undetectable
      probably arose from a lack of money to purchase all prescribed medicines rather
      than deliberate non-compliance. Routine monitoring of anticonvulsant drug levels
      may improve management of epileptic patients.

PMID- 8997851
TI  - Development of renal transplantation as an art and science.

PMID- 8997852
TI  - Asymptomatic rotavirus infection within Benin City urban community, Nigeria.
AB  - This study was carried out in Benin City urban community, Nigeria as a follow-up
      of an earlier study carried out on patients admitted to the University of Benin
      Teaching Hospital. The aim of the present study was to determine the prevalence
      of asymptomatic rotavirus infection amongst urban children and adults. Eight
      hundred and twenty one subjects from 200 homes were screened for rotavirus
      infection between August and December 1990. The 821 stool samples collected from
      the subjects (541 children and 280 adults) were subjected to studies at the
      University of Benin Teaching Hospital. Detection of rotavirus antigen was done by
      the ELISA method. The overall prevalence of asymptomatic rotavirus infection in
      this study was 30.8%. The results reflect a high source of reservoir for spread
      of rotavirus infection within the community.

PMID- 8997853
TI  - Frequency of Helicobacter pylori in gastroscopic biopsy of Ugandan Africans.
AB  - A total of 56 patients who presented for gastroscopy from 1993 to 1995 in Mulago
      Hospital had their gastroscopic biopsy specimens examined for Helicobacter pylori
      (H. pylori). H. pylori was demonstrated in 14 (25%) of the patients. There was no
      sex difference in those with H. pylori infections and the bacteria were only
      found in those above 22 years of age. Fifty six percent of those with the
      infection in which ethnicity was mentioned were Nyankole although they formed
      only 21% of the study group. In all positive cases, H. pylori was found in the
      antrum with accompanying chronic atrophic gastritis.

PMID- 8997854
TI  - Solitary thyroid nodule in Khartoum.
AB  - Ninety four patients with solitary and significantly dominant thyroid nodules
      were studied. Inadequate sampling was reported in 5 patients (5.9%). In the
      remaining 89 patients, 64 had simple goitre (72%), 12 follicular adenoma (13.5%),
      12 were malignant nodules (6 follicular, 5 papillary and one anaplastic) (13.5%)
      and one patient had Hashimoto's thyroiditis. The incidence of malignancy in the
      clinically solitary nodules was 14% (10/70) compared to 10% (2/19) for the
      dominant nodules which increased to 16% (8/49) versus 10% (4/40) respectively
      after ultrasonography and histopathological confirmation of the nature of the
      gland. There is a low positive predictive value for follicular neoplasm with fine
      needle aspiration cytology (FNAC) (44%). This is due to the fact that reports of
      suspicious follicular pattern is agreed not to imply definite malignancy, however
      total lobectomy was done for those patients whereas terms like "not suspicious"
      and "highly suspicious" are considered to mean, benign and malignant respectively
      and in those latter groups the prediction was 100%. The study stresses the
      importance of FNAC techniques in reducing the surgical load with minimal false
      negative results, increasing the yield of carcinoma and projecting the importance
      of a significantly dominant nodule in endemic areas.

PMID- 8997855
TI  - The use of animals in research and ethical considerations.

PMID- 8997856
TI  - Effect of resuscitation on bacterial translocation in haemorrhagic shocked rats.
AB  - The aim of this study was to investigate the resuscitative effects of various
      intravenous solutions on intestinal mucosal damage and bacterial translocation
      due to haemorrhagic shock. Seventy Sprague-Dawley rats were anaesthetised and
      subjected to thirty minutes of haemorrhagic shock (systolic blood pressure 40
      mmHg). Resuscitation was established with either autologous-blood, three per cent
      hypertonic saline (HS), 7.5% HS, 0.9% NaCl and Ringer's lactate and Dextran 70
      solution. Animals in sham shock group were only cannulated and not resuscitated.
      Bacterial translocation was evaluated by culture of mesenteric lymph nodes taken
      24 hours after resuscitation. The rates of bacterial translocation observed were
      50% in autologous blood group, 60% in Dextran 70 group, 40% in Ringer's lactate
      group, 10% each in 3% HS and 7.5% HS group and 20% in 0.9% NaCl group. A
      statistically significant difference was observed between the groups resuscitated
      with HS solution and the other solutions. No meaningful difference was noted
      between the various concentrations of hypertonic saline solution. The reduction
      in the rate bacterial translocation with hypertonic solution is assumed to be due
      to preservation of intestinal microcirculation and thus prevention of intestinal
      ischaemia.

PMID- 8997857
TI  - B-scan ultrasonography in ophthalmic diseases.
AB  - Real time B-scan ultrasonography was utilised on 318 eyes of 298 patients for
      evaluation of 285 (90%) eyes with opaque media; three (1%) eyes, with clear media
      but suspected intraocular abnormalities and for proptosis in 30 (9%) cases. Two
      hundred and nine (66%) eyes had one or more detectable abnormalities. The most
      common abnormality was retinal detachment (39%) followed by vitreous opacities
      (31%), eye ball size abnormalities (12%), intraocular foreign bodies (4%),
      posterior staphyloma (3%) and retinal detachment with vitreous opacities (2%).
      Twenty eight out of thirty patients evaluated for proptosis had abnormal orbital
      tissue patterns. Solid and cystic tissue patterns each accounted for 32% of the
      abnormal orbital studies followed by thyroid orbitopathy (25%), non specific
      (7%), and infiltrative (4%) tissue patterns. Detailed findings of B-scan
      ultrasonographic study is given in this paper. The paper reports further
      experience with the procedure in a developing country. In areas where other
      imaging techniques are not available the procedure is a valuable method of
      evaluating the eye and orbit for any detectable abnormalities and for planning
      management.

PMID- 8997858
TI  - Family planning practices before and after childbirth in Lusaka, Zambia.
AB  - A total of 408 randomly selected normally delivered women who had given birth to
      healthy infants were recruited from a postnatal ward at the University Teaching
      Hospital (UTH) in Lusaka, Zambia. Family planning practices before and after
      pregnancy and delivery were investigated among 376 of these women. The interviews
      were conducted in their homes or at the postpartum clinic at the UTH at the end
      of puerperium. The remaining 32 women, mainly primiparae, were lost to follow-up.
      Thirty four percent of the women had used a family planning method before the
      present childbirth. Most of those (90%) had used modern methods. Women with eight
      and more years of education used modern contraceptive methods more often than
      those with less education. One year after delivery, 64% of the women were using
      modern or traditional family planning methods. Of those who used traditional
      methods, 15% relied on lactational amenorrhoea. Of those who did not use any
      method, 39% indicated that their husbands did not allow them. Fifty-six per cent
      of the teenagers stated that they had no knowledge of family planning, whereas
      84% of the single teenagers had not used contraceptives before. In view of this,
      teenagers and single mothers need a special focus in the development of family
      planning programmes. We also recommend that more research should focus on views
      of both men and women on contraceptive use.

PMID- 8997859
TI  - Echocardiographic findings in Eldoret: retrospective study.
AB  - Echocardiographic (ECHO) findings in 211 consecutive examinations performed at
      Eldoret Medical Services from August 1992 to May 1994 were analysed. Most
      patients were referred by physicians from Eldoret and from the surrounding
      hospitals for assessment of heart failure or a heart murmur. Thirty three
      echocardiograms were judged as being normal and 177 abnormal. Of the abnormal
      ECHOs, congenital heart disease accounted for 38.4% while rheumatic heart disease
      accounted for 40.7%: Of the 68 patients with congenital defects, 21 (30.1%) had
      ventricular septal defects; 19 (27.9%) persistent ductus arteriosus; five (7.5%)
      mitral valve; four (5.9%) tetralogy of Fallot; and three (4.4%) atrial septal
      defects. In addition, there were two (3.0%) patients each with complete atrio
      ventricular septal defects, tricuspid atresia, complete transposition of the
      great arteries, truncus arteriosus, single ventricle and bicuspid aortic valve.
      Of the 67 patients with uncomplicated rheumatic heart disease, mitral valve
      involvement alone was seen in 39 (58.2%), mitral and aortic in 26 (38.8%) and
      aortic valve alone in two (3.0%). Rheumatic heart disease was complicated by
      bacterial endocarditis in five patients. Nine patients had pericardial effusion.
      The possible role of colour-flow ECHO as a feasible, non-invasive and, in the
      long term, cost-effective means of allowing for early detection and timely
      institution of secondary prophylaxis while rheumatic heart disease is still
      asymptomatic is highlighted.

PMID- 8997860
TI  - Prevalence of HBsAg among the non cauterized groups of blood donors.
AB  - One thousand two hundred and seventeen (1217) blood specimens from non-cauterized
      blood donors were tested for HBsAg by counterimmunoelectrophoresis technique: 48
      specimens were positive giving an incidence of 3.95%; specimens from 99 blood
      donors with cautery marks were tested side by side using the same technique, 3
      specimens were positive giving an incidence of 3.05%. These results show that
      Sudan can be considered among the countries with very high prevalence of HBsAg.
      This emphasizes the importance of testing every unit of blood or blood product
      before transfusion. This high prevalence is mainly attributable to the use of
      common improperly sterilized water-boiled syringes, needles and surgical
      instruments. The results also show that the incidence of HBsAg among cauterized
      donors is not higher than among non-cauterized; thus routine rejection of
      cauterized citizens from giving blood at the reception stage is unjustified as it
      adds to the problem of shortage of blood in Sudan.

PMID- 8997862
TI  - Clomiphene citrate therapy and unexplained subfertility.
AB  - Oestrogen receptor (ER) and progesterone receptor (PR) binding site levels were
      determined using an assay system based upon that of King et al. Endometrial
      samples were obtained from 49 subfertility patients on clomiphene citrate
      (Clomid) therapy admitted to hospital for dye laparoscopy. An assay system based
      on that of Kato and Seto using synthetic androgen R1881 was used to measure
      androgen receptor (AR) binding sites in endometrial tissue obtained in the above
      patients. It is concluded that a cyclic variation was observed in ER and PR
      binding sites in women on Clomid therapy. No cyclic variation was observed in AR
      binding sites of women on Clomid therapy.

PMID- 8997861
TI  - Feto-maternal outcome in pre-eclampsia/eclampsia with and without multisystem
      organ failure managed by strict input/output fluid regimen.
AB  - To determine whether peripartum homeostasis can be maintained without invasive
      vascular monitoring, comparison of biological parameters in severe preeclampsia
      (PE)/eclampsia(E) with and without multisystem organ failure (MSOF) was done.
      Twenty six cases of severe PE/E with (n = 13) and without (n = 13) MSOF were
      managed with a strict input/output fluid regimen. Day one pre- and day one
      postdelivery haematology and blood chemistry were performed. MSOF was
      characterised by self-limiting hepato-renal failure and thrombocytopenia. Foetal
      demise was higher with MSOF (53.8%) than without (38.5%), but not significantly
      (chi-square = 0.62). Abruptio placentae was significantly more prevalent without
      (30.8%) than with MSOF (7.7%; chi-square = 5.54). Eclamptic seizures occurred at
      the same rate (46.2 and 30.8%; chi-square = 0.65) with both conditions. There was
      no maternal death. Without invasive vascular monitoring peripartum homeostasis
      can be achieved in severe PE/E with or without MSOF through a strict input/output
      regimen using Ringer's lactate.

PMID- 8997863
TI  - Changing pattern of acute intestinal obstruction in a tropical African
      population.
AB  - A study of one hundred and forty-two patients with acute intestinal obstruction
      over a period of ten years (January 1985-December 1994) at Wesley Guild Hospital
      was undertaken to determine the pattern and outcome of this problem in a tropical
      African population. There was a preponderance of males over females; ratio 1.7:1.
      Mean age was 33 years and over half of the patients were aged between two and 30
      years. There was a second peak age incidence among elderly patients between 50-80
      years. Abdominal pain, vomiting and constipation were common symptoms, while
      abdominal distension and tenderness were common clinical findings.
      Intraperitoneal adhesions were responsible in 41.5%; there was associated
      intestinal volvulus in 25.4% of the cases of intraperitoneal adhesions. In 16.9%,
      strangulated external hernia was responsible for acute intestinal obstruction.
      Small intestinal volvulus was encountered in 20 cases (14.1%) and associated with
      adhesion in 75% of the cases. Intussusception occurred in 14.1% of cases of which
      70% of the patients were below the age of 15 years. In 15 (10.6%) patients, there
      were volvulus of the sigmoid colon, with 80% (12 patients) having gangrenous
      bowel segments. Ascaris were responsible in 3.5% of the patients and large bowel
      tumour in 2.8%. Other rare causes were internal hernia and ileal pseudo
      obstruction. Adhesiolysis and intestinal resection were the commonest operative
      procedures. Common complications were wound infection in 16.2%, postoperative
      fever in 10.6% and chest infection in 9.1%. A mortality rate of 8.4% was
      recorded.

PMID- 8997864
TI  - Transmission of intestinal schistosomiasis in Addis Ababa, Ethiopia.
AB  - Malacological and parasitological surveys were made in Bole-Kotobe area in Addis
      Ababa in April 1996 to investigate the transmission of intestinal
      schistosomiasis. Malacological survey conducted in Kotobe river showed
      Schistosoma mansoni cercarial infection rate of 2.6% (one out of 38) in
      Biomphalaria pfeifferi. In a total of 197 stool specimens from school children
      examined using Kato thin smear method in Misrak Bar Number 1 and Wondirad
      Elementary and Junior Secondary Schools, the overall prevalence rate of
      Schistosomas mansoni was 4% and 10%, respectively while the intensity of
      infection was 66 and 37 eggs per gram (EPG) of stool, respectively. Out of the 13
      children found infected in the two schools, nine gave a history of having swam in
      Kotobe river and had never been outside of Addis Ababa since birth. The
      collection of B. pfeifferi infected with S. mansoni, the establishment of the
      isolated S. mansoni in laboratory mice and the finding of schistosome infected
      children who had never been outside of Addis Ababa confirmed that transmission of
      intestinal schistosomiasis is actually taking place in Addis Ababa. Further
      surveys in other water-bodies in the city for mapping of schistosomiasis
      infection sites and transmission foci are recommended to enable immediate control
      measures before the situation gets out of control.

PMID- 8997865
TI  - Field trial of permethrin impregnated sisal curtains in malaria control in
      western Kenya.
AB  - A trial to determine the effectiveness of sisal eaves-curtains impregnated with
      permethrin for malaria control was conducted in the malaria holoendemic western
      Kenya between 1991 and 1993. Indoor resting densities of Anopheles gambiae s.l.
      and Anopheles funestus were reduced by 90.9% and 93.8% respectively in protected
      houses. The entomological inoculation rate (EIR) was reduced by 72% in the
      intervention village. There was no significant reduction in vector longevity or
      survival as shown by the sustained high sporozoite rates. Monthly bioassays for
      retained insecticidal potency of permethrin on the fibre indicated vector
      mortality rates above 95% over the period. Of 283 and 240 children followed up
      from the intervention and control villages, a mean malaria prevalence of 43.2%
      and 52.2% respectively was observed over the trial period (p < 0.01). The
      prevalence rose to 73.5% and 75.7% (p = 0.541) respectively after the removal of
      the curtains. No significant differences were observed in the mean parasite
      density between the groups or between the proportions with parasite density
      exceeding 2,500 per microliter and with or without fever. The prevalence of
      splenomegaly was significantly lower in the intervention group compared to the
      control, both during (p = 0.005) and after the intervention (p < 0.001). There
      was no significant difference in the mean change in haematocrit at the end of the
      intervention. We observe that permethrin impregnated sisal curtains effectively
      retain permethrin, alter favourably the indoor vector density and EIR, and could
      provide a reduction in malaria prevalence.

PMID- 8997866
TI  - Colonoscopy in the investigation of colonic diseases.
AB  - A retrospective analysis of 640 patients who underwent 681 colonoscopic
      examinations between March 1984 and April 1996 was undertaken. The major
      indications were rectal bleeding (32.8%), change in bowel habit (24.7%),
      abdominal pain (20.1%), abnormal barium enema (9.8%) and iron deficiency anaemia
      (4.8%). Total colonoscopy was performed in 79.3% of cases. The colonoscopic
      finding was normal in 49.8% of patients. Most of the lesions were benign. Polyps
      and carcinoma were found in 9.2% and 7% of patients respectively. 91.3% of the
      lesions were located distal to the splenic flexure and of the remaining proximal
      lesions, polyps and carcinoma accounted for only 2.2%. Rectal bleeding produced
      the highest diagnostic yield (70%) followed by iron deficiency anaemia (61.3%),
      change in bowel habit (48.1%) and abnormal barium enema (47.6%). Lower yields
      were found in patients with abdominal mass (33.3%), follow up colonoscopy (28.6%)
      and abdominal pain (26.9%). However, the diagnostic yield of clinically
      significant pathology varied widely among the different indications. Therefore,
      selection of patients for colonoscopy based on the diagnostic yield of each
      indication may not be practical. Sigmoidoscopy is suggested as the first line of
      investigation for patients suspected to have colonic diseases, particularly where
      there is limited trained manpower and facility. Total colonoscopy should be
      reserved for sigmoidoscopy negative patients with persistent symptoms and high
      risk cases for malignancy.

PMID- 8997867
TI  - Causes of admission of African patients to Gelukspan Hospital, North West
      Province, South Africa.
AB  - An enquiry has been made into the causes of admission in 1994 of African patients
      to Gelukspan Hospital, North West Province, South Africa. The study concerned
      3791 patients of whom 3533 (93.2%) were classifiable. Two groups were not
      included in this number, namely, 1584 'lodgers' (e.g. mothers of infants), and
      1868 females admitted for normal pregnancy. Of the 3533 patients, 940 (26.6%)
      were aged 14 years and younger; 545 (58.0%) these were boys and 395 (42.0%) were
      girls. The main causes of their admission were pneumonia, gastroenteritis,
      trauma, poisoning, and infections. Of the 2593 adults, 1418 (54.7%) were males
      and 1175 (45.3%) females. Among males, chief causes were pulmonary tuberculosis,
      trauma and accidents, congestive cardiac failure, psychosis, cancer and diabetes.
      Of the females, chief causes were pulmonary tuberculosis, trauma and accidents,
      pregnancy related disorders, gastroenteritis, anaemia and pneumonia. Regarding
      other diseases, 4.5% of adults were admitted for cancer, and 1.8% for diabetes.
      The general pattern of admissions is similar to that reported in other rural
      hospitals. The causes of admissions are discussed, regarding; (i) public health
      improvements occurring, and (ii) means of promoting further improvements by
      community self-help, and by help from State health and other services.

PMID- 8997868
TI  - Effects of beta-carotene, flavonoid quercitin and quinacrine on cell
      proliferation and lipid peroxidation breakdown products in BHK-21 cells.
AB  - Exposure of BHK-21 (baby hamster kidney cells) to varying concentration of beta
      carotene (0- 156 nM) induced a reduction in a cell proliferation rate, increased
      lipid peroxidation breakdown products, elevated levels of cellular reduced
      glutathione (GSH), and increased cellular DNA content. Similarly concentration of
      hydrogen peroxide (0-1.0 microM) added to growth medium truncated rates of cell
      proliferation as hydrogen peroxide (H2O2) concentration increased and augmented
      cellular DNA content dramatically. Electrophoresis analysis of DNA from cells
      treated with H2O2 on agarose gel indicated no excessive DNA fragmentation.
      Escalating concentration of flavonoid quercitin (0-10 microM) in culture cell
      medium enhanced the rate of cell growth and diminished levels of lipid
      peroxidation breakdown products. Quinacrine an inhibitor of phospholipase A2
      activity not only abated the decline in cellular lipid peroxidation breakdown
      products but also abridged the rate of cell proliferation. A combination of beta
      carotene (50 nM) and H2O2 (100 microM) added to growth medium depressed cell
      growth further and increased cellular lipid peroxidation breakdown products. High
      levels of lipid peroxidation breakdown products were also evident in newly
      established cultures but these levels decreased with increased growth rate.

PMID- 8997869
TI  - Hypertension in the black community of the Cape Peninsula, South Africa.
AB  - Hypertension prevalence, treatment status and factors relating to high blood
      pressure were determined in an urban black community of the Cape Peninsula, South
      Africa. A study population of 986 subjects aged 15-64 years was randomly
      selected. Blood pressure, height, weight and serum cholesterol levels were
      measured, while demographic information, personal and family history relating to
      hypertension and attendance of health services were determined by questionnaire.
      Overall 9.2% of males and 12.9% of females were hypertensive according to WHO
      criteria. Blood pressures between 160/95 and 140/90 mmHg were found in 10% of
      males and 10.5% of females. The treatment status of hypertensives showed that
      24.3% had a blood pressure below 160/95 mmHg, and 16% below 140/90 mmHg.
      Hypertensives used more alcohol and were more overweight than normotensives.
      Multiple logistic regression revealed that hypertension was independently related
      to age, being overweight and more urbanised. The degree of urbanisation also
      predicted to what extent hypertension prevalence increases with age. This black
      population had low hypertension rates compared with other similar groups in South
      Africa. These data suggest that as rural blacks increasingly undergo
      urbanisation, hypertension prevalence increases. Necessary diagnostic and
      treatment regimens and hypertension services are not yet in place in the South
      African health services, and need to be established.

PMID- 8997870
TI  - Intestinal obstruction in a Saudi Arabian population.
AB  - In a six-year period, fifty-six cases of intestinal obstruction seen and treated
      at Asir Central Hospital since its inception were analysed. Adhesions from
      previous laparotomy scar constituted the commonest cause of intestinal
      obstruction (57.1%). A distant second is faecal impaction (7.1%). Previously
      performed appendicectomy is the commonest cause of adhesions causing intestinal
      obstruction. The interval between surgery and intestinal obstruction varies from
      one month to three years. The pattern of intestinal obstruction seen in this
      environment is more similar to those in the western World or advanced countries,
      than the pattern in the developing countries. This can be explained on the basis
      of the fact that, even though Saudi Arabia is a developing country, the health
      care delivery system is similar to those in developed countries. Fifty percent of
      intestinal obstruction due to adhesions were managed successfully by conservative
      treatment only. About 15% had a failed conservative treatment and had to undergo
      operation. In those cases that required exploration and lysis of adhesions, 43.8%
      also required bowel resection and re-anastomosis.

PMID- 8997871
TI  - Thyroid cancer coexisting with Hashimoto's thyroiditis at King Khalid University
      Hospital, Saudi Arabia.
AB  - A retrospective record review was performed on all patients with thyroid
      carcinoma treated at King Khalid University Hospital (KKUH) during the period
      1985 to 1993. Eighty one cases were identified of which 10 patients had
      coexistent Hashimoto's thyroiditis documented histologically. Of these ten
      patients, nine were females with a mean age of 32.2 years. There was one male
      aged 55 years. Five patients were treated with near total thyroidectomy while the
      others had subtotal thyroidectomy. The relationship between thyroid carcinoma and
      Hashimoto's thyroiditis continues to be a controversial subject. This
      relationship is discussed including the epidemiological and therapeutic
      implications of the coexistence of these two pathologies.

PMID- 8997872
TI  - Duodenal atresia and situs inversus: case report.

PMID- 8997873
TI  - Lack of association between ABO blood groups and Rh factor and the tendency to
      develop mycetoma.

PMID- 8997874
TI  - Bone involvement in childhood acute lymphoblastic leukaemia.

PMID- 8997875
TI  - Excess dietary urea intake in ewes and its effect on ovulation rate and embryo
      development.
AB  - The effect of excess dietary urea on ovulation and early embryo development of
      sheep was studied. Thirty Border Leicester x Scottish Black face ewes randomly
      assigned to three treatments were given a basal control diet (C) which met energy
      requirements for body weight maintenance. Other treatments were basal diet plus
      24 g of urea/day (low urea, L) or plus 48 g (high urea, H)/day. The reproductive
      cycles of the ewes were synchronized using a single injection of prostaglandin
      (PGF2 alpha) and progesterone by an intravaginal controlled internal drug release
      (CIDR) device for 12 days. Ovulation was induced by the use of pregnant mare
      serum gonadotrophin (PMSG). Ewes were inseminated approximately 52 hours after
      CIDR device removal using a laparoscopic technique. Embryos were recovered at Day
      4 or Day 11 after insemination from half of the ewes from each treatment group.
      There were no significant differences in ovulation rates among the three groups.
      The embryo recovery rates were not affected by day of recovery. At embryo
      recovery on Day 4, 7/13 in C, 3/6 in L and 0/7 in H embryos were morulae. After
      72 hours of in vitro culture 6/10 in C, 2/3 in L and 0/4 in H embryos developed
      to the blastocyst stage. Pregnancies sustained were C 6/8, L 5/7 and H 1/3 of the
      autotransfers. Throughout the experiment plasma urea levels were significantly
      affected by diet (p < 0.01). Plasma ammonia levels in the H group were
      significantly higher than those in the C and L groups (p < 0.05) for 4 hours
      after each feed. There was no treatment effect on plasma progesterone
      concentration. The luteinizing hormone (LH) surge onset time and amplitude were
      not correlated to ovulation rate and were not affected by treatment. It is
      concluded that high circulating concentrations of plasma urea and ammonia have an
      adverse effect on early embryo development. This effect was independent of any
      alterations in progesterone and LH concentrations.

PMID- 8997876
TI  - Immunomodulative effects of bovine immunodeficiency-like virus (BIV)-infection
      and mixed infection of BIV and bovine leukemia virus on sheep.
AB  - Experimental bovine immunodeficiency-like virus (BIV)-infection and mixed
      infection of BIV and bovine leukemia virus (BLV) were performed on sheep. BIV
      proviral DNA and anti-BIV antibodies were persistently detected in all BIV
      inoculated sheep. A slight increase in lymphocyte counts was observed in BIV
      infected sheep, but the percentages of CD4+ and CD8+ cells in sheep peripheral
      blood mononuclear cells (PBMCs) were not significantly changed. A transient
      decrease in lymphocyte blastogenic response to concanavalin. A was observed in
      two of three BIV-infected sheep at 3-6 months after inoculation. From 6 months
      after BLV-inoculation to sheep which were previously infected with BIV, the
      numbers of lymphocytes expressing a tumor-associated antigen (TAA) of bovine
      leukosis were increased compared to those of a sheep inoculated with BLV alone.
      The BLV titers in PBMCs and the antibody titers against BLV from sheep infected
      with both BIV and BLV were higher than those of a sheep inoculated with BLV
      alone.

PMID- 8997877
TI  - Detection of viral genome in non-neural tissues of cattle experimentally infected
      with bovine herpesvirus 1.
AB  - To obtain further information on the latent infection with bovine herpesvirus 1
      (BHV-1) in the natural host, we examined the nasal secretions and various tissues
      of experimentally infected calves using virus isolation, polymerase chain
      reaction (PCR), and immuno-PCR/antigen (Immuno-PCR/Ag) assays. In the nasal
      secretions, viral DNA was detected in samples with virus isolation titers of
      10(4.3) TCID50 or more by PCR. On the same samples, Immuno-PCR/Ag remained
      positive up to day 19 p.i. the last day of test. BHV-1 DNA was detected from the
      following tissues in all the calves at day 22 p.i.: trigeminal ganglia, ovaries,
      lungs, nasal and tracheal mucosae, spleen, prescapular and precrural lymph nodes,
      and peripheral blood leukocytes (PBL), but not skeletal muscles. Virus was not
      recovered from any of these tissues. The present findings suggest a possible role
      of leukocytes in BHV-1 latent infection.

PMID- 8997878
TI  - Bovine clostridial infections in Zambia (1985-1994).
AB  - Retrospective surveillance study of clostridial infections of cattle in Zambia,
      for the period 1985 to 1994, showed that out of the 318 cases observed, 62.8% and
      24.2% were from Western and Southern provinces, respectively. Of the 6 clostridia
      species identified, Clostridium septicum (38.1%) followed by C. chauvoei (36.2%)
      and C. perfringens (13.2%) were dominant. Although the highest incidence for
      clostridial infections was in 1989 (75 cases) and 1990 (77 cases), the number of
      C. perfringens cases seemed to increase. More cases were found in the dry season
      until the onset of the rains, that is, the period August to December.

PMID- 8997880
TI  - The road more traveled.

PMID- 8997881
TI  - Integrity and ethics in medicine.

PMID- 8997882
TI  - Carotid endarterectomy in Oklahoma Medicare beneficiaries: patient
      characteristics and outcomes.
AB  - BACKGROUND AND OBJECTIVES: Ischemic stroke represents the third leading cause of
      death and the most common cause of permanent disability in the United States.
      Carotid endarterectomy has been widely utilized as a procedure to reduce the risk
      of stroke and represents the most commonly performed peripheral arterial surgery.
      This cooperative project was initiated to assess the appropriateness of carotid
      endarterectomies performed on Medicare beneficiaries and the postoperative
      outcomes (mortality and stroke) in these patients. METHODS: Retrospective review
      was performed on the inpatient medical records of 774 patients who underwent 813
      carotid endarterectomy procedures in eight hospitals during calendar years 1993
      and 1994. Medicare claims data were also analyzed for all carotid
      endarterectomies performed in Oklahoma during calendar years 1992 through 1995.
      RESULTS: A history of transient ischemic attack or stroke in the distribution of
      the operated carotid artery was documented in 57% of the cases. The majority of
      patients had preoperative ultrasound imaging of the carotid arteries and a
      preoperative angiogram was performed before 96% of the procedures. Accepted
      indications for the surgery were documented for 98% of the procedures. Stroke or
      death within 30 days of the date of the carotid endarterectomy occurred after
      4.9% (0-8.8% by hospital) of the procedures. CONCLUSIONS: This project
      demonstrated considerable variation between hospitals in the outcomes of patients
      undergoing carotid endarterectomy and the potential for improved care of patients
      with regard to discharge planning, education, and use of anticoagulant or
      antiplatelet medications postoperatively.

PMID- 8997883
TI  - The merits of varicella vaccination for varicella non-immune health care workers.
AB  - Immunity against varicella can be reliably established by history and, if
      negative, confirmed or refuted by serology. If non-immune, the merits of
      varicella vaccine for a health care worker (HCW) can be stated clearly:
      Protection from a disease which may be particularly severe in an adult, and
      evading the inconvenience (investigation time and possible work restriction) and
      cost of managing an exposure. This paper discusses implementation of a varicella
      immunity program for HCWs at Columbia Presbyterian Hospital in Oklahoma City.

PMID- 8997879
TI  - Ultrasonography and angiographic examination of normal canine liver vessels.
AB  - The aim of this study is to provide a description of the ultrasonographic and
      angiographic anatomy of the hepatic and portal veins in normal dogs. Knowledge of
      this anatomy is essential for the proper diagnosis and correction of hepatic
      vessel anomalies like portal systemic shunts. Cranial mesenteric portography was
      done in 10 adult mongrel dogs to visualize the portal vein and its branches while
      the hepatic veins were visualized using the transvenous retrograde angiography
      method. Longitudinal and transverse ultrasound scans of the liver were done in
      the same dogs in left and right lateral positions in order to determine the best
      positions for imaging the different liver vessels. The distribution pattern of
      the hepatic and portal veins could be demonstrated by both ultrasonography and
      contrast angiography. Hepatic arteries are not usually visualized
      ultrasonographically. Ultrasound provided dynamic information that could not be
      obtained by contrast radiography. Super imposition of all vessels in the
      angiographic studies made the description of the branches of the liver vessels
      difficult. The results of the present study suggest that both methods may provide
      important complementary information in the diagnosis and planning of surgical
      procedures for the correction of vessel anomalies in the canine liver.

PMID- 8997884
TI  - OAFP starts practice-based resource/research network.
AB  - The Oklahoma Academy of Family Physicians, in collaboration with the University
      of Oklahoma Health Sciences Center, has established a primary care practice-based
      research network with thirteen family practice offices currently participating.
      The practices are connected to each other and to the Health Sciences Center
      campuses in Oklahoma City and Tulsa by electronic mail and have begun their first
      research project involving the diagnosis and treatment of brown recluse spider
      bites in the primary care setting.

PMID- 8997885
TI  - Prenatal weight gain and birth weight among Oklahoma mothers.

PMID- 8997886
TI  - The neighborhood context of adolescent mental health.
AB  - Mental health disorders in adolescence are pervasive, often carry into adulthood,
      and appear to be inversely associated with social status. We examine how
      structural aspects of neighborhood context, specifically, socioeconomic
      stratification and racial/ethnic segregation, affect adolescent emotional well
      being by shaping subjective perceptions of their neighborhoods. Using a community
      based sample of 877 adolescents in Los Angeles County, we find that youth in low
      socioeconomic status (SES) neighborhoods perceive greater ambient hazards such as
      crime, violence, drug use, and graffiti than those in high SES neighborhoods. The
      perception of the neighborhood as dangerous, in turn, influences the mental
      health of adolescents: the more threatening the neighborhood, the more common the
      symptoms of depression, anxiety, oppositional defiant disorder, and conduct
      disorder. Social stability and, to a lesser extent, social cohesion, also emerge
      as contributors to adolescent disorder. This investigation demonstrates that
      research into the mental health of young people should consider the socioeconomic
      and demographic environments in which they live.

PMID- 8997887
TI  - Family, work, and access to health insurance among mature women.
AB  - We use a life course approach to address much ignored variation in access to
      health insurance. Using data from the National Longitudinal Survey of Mature
      Women, we reinterpret the role of both family and employment characteristics in
      shaping coverage. Mature women are more likely to be insured as wives than as
      workers, but that safety net is only available to married women. As a result,
      unmarried women are two to three times as likely to be uninsured or to rely on
      public programs such as Medicaid. And because they are significantly less likely
      to be married to a covered worker, Black women are two to three times more likely
      to be uninsured or to rely on public programs. Given rising instability in
      employment and marital status across the life course, stable health insurance
      coverage can only be attained by universal rather than employment-based or family
      based schemes.

PMID- 8997888
TI  - The effects of family composition, health, and social support linkages on
      mortality.
AB  - This study reveals how family living arrangements influence mortality. I use the
      National Health Interview Survey, Supplement on Aging, and discrete-time hazard
      rate models to show that some family arrangements result from strong social
      bonds, but others are a result of financial needs or health problems. In some
      instances, it is not family living arrangements that influence the risk of
      mortality but vice versa: The family rearranges itself to deal with ill health
      and disability among its members. The family strives to promote health, prevent
      disease, and encourage economic security. However, family members who endure
      economic or health hardships face increased risk of death.

PMID- 8997889
TI  - Alcohol disorders in young adulthood: effects of transitions into adult roles.
AB  - Using data gathered prospectively, the authors examined whether transitions in
      two major adult social roles, marriage and parenthood, influence the risk of
      developing (1) DSM-III-R alcohol disorder and (2) symptoms of alcohol disorder.
      Additionally, the potential impact of these transitions on persistence of alcohol
      disorder was examined. In the study, 1,007 members (21 to 30 years old) of a
      large health maintenance organization located in southeast Michigan were
      interviewed initially in 1989, 979 of whom were reinterviewed in 1992. Incidence
      of alcohol disorder symptoms was significantly higher among those who remained
      single (RR = 2.1) or became divorced (RR = 6.0) during the follow-up period,
      compared to those getting or staying married. Those who were never parents
      through the follow-up were also at increased risk (RR = 2.5), relative to those
      who became parents for the first time. Similar results were obtained for the
      incidence and persistence of an alcohol disorder. Transitions into adult roles,
      such as marriage and parenthood, appear to reduce the risk of developing alcohol
      disorder or related symptoms in young adulthood. These transitions also reduce
      the likelihood that an existing alcohol disorder will persist.

PMID- 8997890
TI  - Ethnic differences in temporal orientation and its implications for hypertension
      management.
AB  - Research indicates that health beliefs and perceptions are shaped and organized
      by life experiences. Time perception, also structured by life experiences, can
      systematically alter individuals' perceptions of disease and evaluations of
      treatment options. Using the Health Belief Model (HBM), this study examines the
      effects of ethnicity and hypertension temporal orientation on the health
      perceptions of 300 African Americans and White Americans with hypertension.
      Results revealed that African Americans were more present-oriented than White
      Americans regarding their daily experiences with managing hypertension. Compared
      to more future-oriented respondents, present-oriented people perceived themselves
      to be less susceptible to the consequences of hypertension, believed more in the
      benefits of home remedies and negative aspects of prescribed medication, and
      believed less in the benefits of prescribed medication and negative aspects of
      home remedies. We concluded that ethnicity influences hypertension temporal
      orientation and that hypertension temporal orientation affects perceptions about
      hypertension and its management. Implications for health and medical care are
      addressed.

PMID- 8997891
TI  - Age and the gender gap in depression.
AB  - Women average higher levels of depression than men. This paper tests the
      hypothesis that the gender gap in depression grows in adulthood as women and men
      enter and undergo their unequal adult statuses. The emerging gender
      stratification hypothesis has three parts: (1) The age increment hypothesis
      states that the difference in depression between women and men increases in
      successively older age groups at least until retirement age and perhaps
      throughout the lifetime; (2) The status mediation hypothesis states that rising
      sex differences in marital status, employment, house-work, child care, and
      economic strains account for much of the larger gender gap in depression among
      middle-aged adults than among young adults; (3) The differential change
      hypothesis states that women's depression drops more slowly than men's in early
      adulthood, so that the gender gap increases over time as implied by the
      concurrent differences among age groups. Analyses of three data sets (two from
      national U.S. samples) support the three component hypotheses.

PMID- 8997892
TI  - A time-series test of the quarantine theory of involuntary commitment.
AB  - Persons believed to be mentally ill and imminently violent are often subjected to
      coerced treatment. Among the justifications for this practice is the argument
      that removing such people from the community is analogous to quarantine. We test
      the quarantine theory using daily data from San Francisco. Results suggest that
      the incidence of coerced treatment of males is inversely related to assaults and
      batteries by males one day later. The finding implies that persons who are
      involuntarily committed are at elevated risk of violent behavior. The
      implications of the findings for the prevention of assaultive behavior are
      briefly described.

PMID- 8997893
TI  - A picomole-scale method for charge derivatization of peptides for sequence
      analysis by mass spectrometry.
AB  - A highly activated ester containing a fixed positive charge, S-pentafluorophenyl
      [tris(2,4,6-trimethoxyphenyl)phosphonium]acetate bromide (TMPP-AcSC6F5 bromide),
      has been synthesized as a reagent for N-terminal modification of peptides. Stable
      in aqueous acetonitrile solution during extended storage, TMPP-AcSC6F5 bromide
      reacts with unprotected peptides through p-(dimethylamino)pyridine (DMAP)
      promoted amidation in aqueous acetonitrile (15 min, ambient temperature) to form
      N-TMPP-Ac derivatives of peptides. These peptide derivatives are readily amenable
      to analysis by fast atom bombardment (FAB) and matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry. Greater than 90% conversion has
      been observed in transforming low-nanomole quantities of analyte using molar
      ratios of 1:5:10 (peptide/reagent/ DMAP). For reactions at the picomole level a
      slightly modified stoichiometry, with molar ratios of 1:10:500, is employed.
      Owing to the high reaction efficiency and the tolerance to moderate excess
      reagent and base during analysis by FAB- and MALDI-MS, the reaction mixture
      containing the modified peptides can be analyzed directly in most cases, without
      sample cleanup. Examples of the preparation and analysis of a variety of N-TMPP
      acetyl-peptides (TMPP-Ac-peptides) ranging from hexamers to 15-mers are given.
      Collisionally activated dissociation tandem mass spectrometry of TMPP-Ac
      derivatives showed dominant a-type ions, accompanied by d- and c-type ions in
      some cases, allowing sequence determination to be made in a straightforward
      manner.

PMID- 8997894
TI  - Assessment of heterogeneity in antibody-antigen displacement reactions.
AB  - The intrinsic binding characteristics of monoclonal antibodies are modified upon
      immobilization onto a solid-phase matrix. Factors such as the distribution in
      affinity must therefore be taken into consideration in order to predict the
      kinetics of antibody binding at solid-liquid interfaces. A mathematical analysis
      is presented herein that allows the assessment of heterogeneity in the affinity
      of monoclonal antibodies immobilized onto a solid support. This model is based on
      a modified version of the Sips distribution function adapted to the conditions of
      a solid-phase displacement assay in flow. An assay for trinitrotoluene (TNT)
      provides the data to evaluate the extent of heterogeneity introduced by
      immobilization of antibodies in a flow immunoassay. We determined the index of
      antibody heterogeneity on two solid supports, controlled-pore glass beads and
      agarose beads, coated with a monoclonal anti-TNT antibody at varying densities.
      The data confirm that the threshold for crossover from homogeneous to
      heterogeneous forms of the reaction isotherm is different in displacement
      reactions than in association-dissociation reactions. Our analysis shows that the
      measured displacement isotherm is consistent with a homogeneous or only
      moderately heterogenous distribution of relative affinities.

PMID- 8997895
TI  - Measurement of ascorbate and dehydroascorbate contents in biological fluids.
AB  - Instabilities of ascorbate and dehydroascorbate throughout sample processing are
      clearly a significant aspect of quantifying of them. Contents of ascorbate in
      biological fluids decrease with measurable oxidation occurring within minutes to
      hours. Similarly, dehydroascorbate disappears with chemical or enzymatic
      degradation within minutes. The half-life of dehydroascorbate in human
      heparinized plasma was approximately 2 min. These results indicated that the
      amount of dehydroascorbate present in sample solutions is a function of both the
      oxidation of ascorbate and the degradation of dehydroascorbate during the
      processing of biological fluids. To quantify ascorbate and dehydroascorbate
      concentrations in biological fluids including circulating blood plasma and urine,
      we established a high-performance liquid chromatographic method, which requires
      no pretreatment of sample solutions.

PMID- 8997896
TI  - Synthesis and antifungal activities of myristic acid analogs.
AB  - Myristic acid analogs that are putative inhibitors of N-myristoyl-transferase
      were tested in vitro for activity against yeasts (Saccharomyces cerevisiae,
      Candida albicans, Cryptococcus neoformans) and filamentous fungi (Aspergillus
      niger). Several (+/-)-2-halotetradecanoic acids including (+/-)-2
      bromotetradecanoic acid (14c) exhibited potent activity against C. albicans (MIC
      = 39 microM), C. neoformans (MIC = 20 microM), S. cerevisiae (MIC = 10 microM),
      and A. niger (MIC < 42 microM) in RPMI 1640 media. Improved synthetic methods
      have been developed for the synthesis of 12-fluorododecanoic acid (12a) and 12
      chlorododecanoic acid (12c). Three novel fatty acids, 12-chloro-4-oxadodecanoic
      acid (8a), 12-phenoxydodecanoic acid (12i), and 11-(4-iodophenoxy)-undecanoic
      acid (13d) were also synthesized and tested.

PMID- 8997898
TI  - Synthesis and antitumour activity of new derivatives of flavone-8-acetic acid
      (FAA). Part 1: 6-Methyl derivatives.
AB  - A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl
      substituent have been prepared and their anti-tumour activity evaluated in vitro
      against a panel of human and murine tumour cell lines and in vivo against MAC
      15A. While many of the compounds show activity comparable to FAA in vitro, this
      essentially disappears in vivo, possibly due to degradation before the compounds
      can reach the tumour site.

PMID- 8997897
TI  - 3-(3,5-Dimethyl-4-octadecanoylpyrrol-2-yl)propionic acids as inhibitors of 85 kDa
      cytosolic phospholipase A2.
AB  - 3-(1,4-Diacylpyrrol-2-yl)propionic acids were designed as inhibitors of cytosolic
      phospholipase A2. Enzyme inhibition was assayed by evaluation of calcium
      ionophore A23187-induced arachidonic acid release from bovine platelets. While
      the synthesized bisacyl compound 3-[3,5-dimethyl-4-octadecanoyl-1-(3
      phenylpropionyl)pyrrol-2-yl] propionic acid was inactive at 33 microM, the
      related monoacylated 3-(3,5-dimethyl-4-octadecanoylpyrrol-2-yl)-propionic acid
      and 3-(1,3,5-trimethyl-4-octadecanoylpyrrol-2-yl)-propionic acid proved to be
      inhibitors of cytosolic phospholipase A2(IC50: 24 microM and 13 microM,
      respectively).

PMID- 8997899
TI  - Synthesis and activity of the glutathione analogue gamma-(L-gamma-oxaglutamyl)-L
      cysteinyl-glycine.
AB  - An efficient synthesis of the backbone modified glutathione analogue gamma-(L
      gamma-oxaglutamyl)-L-cysteinyl-glycine (7), characterized by the presence of an
      urethane O-CO-NH linkage replacing the gamma-glutamylic CH2CO-NH fragment is
      described. The new analogue has been fully characterized by 1H- and 13C-NMR, and
      FAB-MS. Compound 7 was tested for inhibition of gamma-glutamyl-transferase
      activity and was found to be a non-competitive inhibitor of hog kidney gamma
      glutamyltransferase (EC 2.3.2.2).

PMID- 8997900
TI  - Phosphono analogues of glutathione as new inhibitors of glutathione S
      transferases.
AB  - Phosphono-analogues of glutathione containing the O = P(OR)2 moiety in place of
      the cysteinyl residue CH2SH 1a-1d were prepared by solution phase peptide
      synthesis. Benzyl, benzyloxy-carbonyl, and tert-butyl protecting groups were used
      to mask the individual amino acid functional groups. The formation of peptide
      bonds was achieved by the usual peptide synthesis via activation of carboxylic
      functions with cyclohexylcarbodiimide and subsequent reaction with free amino
      groups. The thus obtained, fully-protected peptides were each purified by normal
      phase column chromatography. Deprotection was accomplished by hydrogenolysis and
      by treatment with HBr/acetic acid yielding the desired phosphonic acid diester 1a
      1d. The inhibition of the glutathione conjugation of 1-chloro-2,4-dinitrobenzene
      by human placental glutathione S-transferase was studied by determining the IC50
      values of the new glutathione analogues. The IC50 values were 291 microM, 139
      microM, 64 microM, and 21 microM for the dimethyl, diethyl, diisopropyl, and di-n
      butyl esters, respectively. The results clearly show that the formal substitution
      of the glutathione thiol function by phosphonic acid esters leads to a new class
      of glutathione S-transferase inhibitors. Further investigations directed at the
      question of whether or not these glutathione analogues are suitable for a
      modulation in chemotherapy are in progress.

PMID- 8997901
TI  - New NO-donors with antithrombotic and vasodilating activities, Part 14. 1,3,4
      Triazol-1-oles.
AB  - Five 1,3,4-triazol-1-oles (5a-f) with different alkyl, aryl, and arylalkyl
      substituents in 2,5-position were synthesized and tested for their antithrombotic
      properties. The 2,5-dimethyl derivative 5a was most active. 2 h after
      administration of 60 mg/kg to rats thrombus formation by a laser beam was
      inhibited by 42% in arterioles and by 33% in venules. At the same dose the blood
      pressure of SHR rats was slightly (5%) but significantly decreased even 4 h after
      application of 5a. This pattern of activities suggests a nitric oxide mediated
      mechanism of action. 1,1'-Azo-bis-ethanone oxime(7)-the synthetic precursor of 5a
      inhibited the aggregation of blood platelet (Born test) with an IC50 = 15
      mumol/L.

PMID- 8997902
TI  - Clinical and anatomic features of the inguinal canal during hernia.
AB  - Seventy-eight patients affected by inguinal hernia, 33 by direct and 45 by
      indirect external oblique types, were studied. The morphologic and structural
      aspects of the inguinal canal including its length, the diameter of the deep
      inguinal ring and the qualitative features of the fascia transversalis and
      aponeuroses of the external and internal oblique muscles and of the transversus
      muscle were investigated. In all 78 patients with inguinal hernia, the length of
      the canal was 4.7 cm. In the 33 patients with direct inguinal hernia the width of
      the deep inguinal ring varied from 1.5 to 2.5. The aponeurosis of the external
      oblique muscle was dense in 19 cases (57.58%), rather laddered in 10 (30.30%) and
      very laddered in 4 (12.12%). The fascia transversalis was discontinued in 28
      cases (84.85%) and velamentous in 5 cases (15.15%). In the 45 patients with
      indirect inguinal hernia the width of the deep inguinal ring varied from 1.5 to 7
      cm. The aponeurosis of the external oblique muscle was dense in 14 cases
      (31.11%), rather laddered in 23 cases (51.11%), very laddered in 8 (17.78%). The
      fascia transversalis was dense in 15 (33.33%), elastic in 17 (37.78%) and
      velamentous in 13 cases (28.89%). Based on the results of this study, a series of
      therapeutic considerations are set forth. The most important of these include
      early surgical intervention, which is absolutely necessary, and the use of
      prostheses in the inguinal canal.

PMID- 8997903
TI  - The inner diameter of human intracranial vertebral artery by color Doppler
      method.
AB  - In 50 healthy subjects the internal diameter of the intracranial vertebral artery
      were measured by echocolor doppler method. The diameter of left vertebral a. was
      greater than that of the right in most subjects (58%); the mean left/right
      difference was statistically significant (p < 0.05). Analyzing men and women
      separately, the difference remained significant only in women (p < 0.05). A
      significant correlation was found between vertebral a. diameter and sex (p <
      0.01). The vertebral a. diameter had a tendency to increase with age, that
      reached significance only for the left vertebral one. No significant correlation
      was found between body surface area and vertebral a. diameter.

PMID- 8997904
TI  - Collateral circulation in occlusion of lower limbs arteries: an anatomical study
      and statistical research in 35 old subjects.
AB  - The collateral circles formed following lower limbs arterial occlusion and their
      hemodynamic function have been described; 35 subjects (23 men and 12 women; age
      range 65 to 80), with symptomatic lower limbs obstructive arteriopathy
      (Fontaine's stage II) following occlusion of vessels downstream the subrenal
      aorta have been studied by means of Contrast Angiography and Color Doppler
      Echography of the vascular district including the terminal aorta and the lower
      limbs arteries. The hemodynamic significance of the collateral circles was
      assessed by calculating the Windsor index. In this population, the collateral
      circles for each level of obstruction were explored. Occlusion of the terminal
      abdominal aorta: the collateral circle was mainly established through the
      inferior mesenteric and ischiatic arteries and through the lumbar, ilio-lumbar
      and gluteal arteries; occlusion of the iliac tract: the collateral circulation
      was established through the spermatic or ovaric artery and through the funicular,
      external pudendal and middle sacral arteries; occlusion of the ilio-femoral
      tract: the collateral circulation was formed by the internal and external
      pudendal arteries and by the ilio-lumbar, obturating, gluteal and circumflex
      iliac arteries; occlusion of first tract of the superficial femoral artery:
      collateral circulation was established through the deep femoral artery and
      through the perforating arteries; occlusion of the terminal tract of the
      superficial femoral artery: collateral circulation was formed by the articular
      branches of the same artery originating proximal to the occlusion and through
      branches of the deep femoral artery; occlusion of the superficial and deep
      femoral arteries at their origin: collateral circulation was established through
      the ischiatic artery (directly and, indirectly, through the perforating
      arteries), and through the tegumental arteries. The hemodynamic significance, as
      measured by Windsor index was higher the more proximal was the occlusion, in
      accord with the lower caliber and/or number of vessels involved in the collateral
      circles.

PMID- 8997905
TI  - Structure and ultrastructure of the bone/ligament junction.
AB  - The tibial insertion of the patellar ligament of rat was investigated at light
      microscopy, scanning electron microscopy and transmission electron microscopy.
      Until the point of insertion, the patellar ligament showed the typical structure
      of a tendon. In proximity to the insertion, the ligament increased in diameter
      and was gradually infiltrated by a different, cartilage-like matrix. Its
      tenocytes became progressively rounded and displayed some characteristics of
      chondrocytes. Tendon fibres crossed this fibrocartilage and arrived well beyond
      the mineralization front. Finally, they appeared to interweave with the tibial
      diaphysis bone. These fibres were always distinct from the interposed
      extracellular matrix and exhibited a different pattern of mineralization from the
      matrix. Our observations indicate that fibrocartilage does not supersede tendon
      but merely infiltrates it. Thus, the tendon does not splay during articular
      movement and the tensile stress is redistributed across the insertion area by
      increasing the mechanical coupling among adjacent fibres. At the same time, this
      mechanism provides a structural, uninterrupted connection from tendon to bone
      which is consistent with the biomechanical requirements it has to withstand.

PMID- 8997906
TI  - Internal diameters of human femoral blood vessels in 50 healthy subjects using
      color Doppler ultrasonography.
AB  - 50 healthy subjects (25 men and 25 women; age range: 18 to 80 years) have been
      examined. The internal calibers of the common femoral artery, of the superficial
      femoral artery, of the common femoral vein, and of the superficial femoral vein
      have been measured in selected locations using Color Doppler Ultrasonography. The
      difference in vessel caliber between men and women was statistically significant
      (p < 0.01). There was no significant difference in left versus right vessel
      calibers for all the four vessels studied. In the same subject, vessel caliber
      was directly proportional in the left compared to the right side (p < 0.01). Both
      in the left and in the right side, arterial and venous calibers of the same
      subject in the same side were directly proportional (p < 0.01). The relationship
      between the calibers of the four vessels under study and age, height, and body
      surface area were not statistically significant.

PMID- 8997907
TI  - Magnetic resonance angiographic evaluation of circulus arteriosus cerebri (circle
      of Willis): a morphologic study in 100 human healthy subjects.
AB  - The Circle of Willis was studied by Magnetic Resonance Angiography in 100 healthy
      subjects. In 41% of these cases, the arteries were arranged in the classically
      described way. In 21%, hypoplasia of the posterior communicating as. was noted,
      while in 13% the posterior cerebral as were found to originate from the internal
      carotid a.. In 9% of these cases, three anterior cerebral as. were present. In 3%
      the anterior communicating artery could not be identified, while the left
      posterior communicating artery was hypoplastic. In 2% the absence of a posterior
      communicating artery was associated with the origin of a posterior cerebral a.
      from the internal carotid. In another 2% the anterior cerebral as. were partially
      fused, and in yet another 2%, hypoplasia of both an anterior and a posterior
      cerebral a. was present. The remaining seven cases (7%), all different from each
      other, represented combinations of the above described variations. Statistical
      analysis indicated that anomalies occurred more commonly on the left than on the
      right side. The morphology of the Circle of Willis could not be correlated with
      either sex or Body Index.

PMID- 8997908
TI  - Final act.

PMID- 8997909
TI  - Change is the most bitter pill.

PMID- 8997910
TI  - "For the love of money is the root of all evil": exorcising some demons from our
      health care system.

PMID- 8997911
TI  - An unbecoming act.

PMID- 8997912
TI  - Dr. Morgan's parable.

PMID- 8997913
TI  - There is still a place for the idealism of the round table.

PMID- 8997914
TI  - Everyman and managed care.

PMID- 8997915
TI  - Risk factors for depression in rheumatoid arthritis.
AB  - OBJECTIVE: To identify risk factors for the development of depression in persons
      with rheumatoid arthritis (RA). METHODS: Subjects were divided into depressed
      versus nondepressed groups on the basis of the Center for Epidemiologic Studies
      Depression Scale; a range of psychological, pain-related, disease-related, and
      demographic variables were analyzed to predict depression. Both cross-sectional
      and longitudinal predictive models were examined. RESULTS: A series of analyses,
      including multiple logistic regression, found that the optimal predictors of
      depression in RA were average daily stressors, confidence in one's ability to
      cope, and degree of physical disability. The model was successfully cross
      validated on separate data sets (i.e., same subjects at different time points).
      CONCLUSION: All of the identified risk factors for depression in RA are
      preventable to some extent and, therefore, should be addressed in comprehensive,
      rheumatology team care.

PMID- 8997916
TI  - Self-reported functional status in osteoarthritis of the knee in a rural southern
      community: the role of sociodemographic factors, obesity, and knee pain.
AB  - OBJECTIVE: This study examined the roles of sociodemographic factors (age, race,
      gender, education, marital status), obesity, and severity of radiographic knee
      osteoarthritis (OA) and knee pain on self-reported functional status. METHODS:
      The sample included 1,272 African-American and Caucasian individuals, aged 45
      years or older, from the Johnston County Osteoarthritis Project. Analysis of
      variance was used to assess variation in mean Health Assessment Questionnaire
      (HAQ) scores by the above variables. RESULTS: Mean HAQ scores differed by
      severity of radiographic knee OA and knee pain, obesity, and all demographic
      factors (P < 0.0001), except race. Only age, female sex, obesity, and knee pain
      severity were independent effects (P < 0.0009). Disability associated with knee
      pain varied by both radiographic knee OA severity and obesity. CONCLUSIONS: Knee
      pain severity was more important than radiographic knee OA severity in
      determining disability. Obesity was independently associated with disability and
      compounded disability from knee pain. Studies of disability in knee OA should
      include assessment of obesity, severity of radiographic knee OA, and severity of
      knee pain, as well as their interactions.

PMID- 8997918
TI  - Patient education interventions in osteoarthritis and rheumatoid arthritis: a
      meta-analytic comparison with nonsteroidal antiinflammatory drug treatment.
AB  - OBJECTIVE: To compare the effects of education interventions and nonsteroidal
      antiinflammatory drug (NSAID) treatment on pain and functional disability in
      patients with osteoarthritis (OA), and on pain, functional disability, and tender
      joint counts in patients with rheumatoid arthritis (RA). METHODS: Two meta
      analyses were performed: one of controlled trials of patient education
      interventions and one of placebo-controlled trials of NSAID treatments. RESULTS:
      Nineteen patient education trials comprised of 32 treatment arms and 28 NSAID
      trials comprised of 46 treatment arms were included. The weighted average effect
      size for pain was 0.17 in the education trials and 0.66 in the NSAID trials. The
      average effect size for functional disability was 0.03 in the education trials
      and 0.34 in the NSAID trials; effects of education were much larger in RA studies
      than in OA studies. In RA studies, the average effect size for the tender joint
      count was 0.34 in the education trials and 0.43 in the NSAID trials. Because most
      patients in the education trials were being treated with medications, the effect
      sizes of these trials represent the additional, or marginal, effects of patient
      education interventions beyond those achieved by medication. CONCLUSIONS: Based
      on this meta-analysis, patient education interventions provide additional
      benefits that are 20-30% as great as the effects of NSAID treatment for pain
      relief in OA and RA, 40% as great as NSAID treatment for improvement in
      functional ability in RA, and 60-80% as great as NSAID treatment in reduction in
      tender joint counts in RA.

PMID- 8997917
TI  - Spouse-assisted coping skills training in the management of osteoarthritic knee
      pain.
AB  - OBJECTIVE: To evaluate the effects of a spouse-assisted pain-coping skills
      training intervention on pain, psychological disability, physical disability,
      pain-coping, and pain behavior in patients with osteoarthritis (OA) of the knees.
      METHODS: Eighty-eight OA patients with persistent knee pain were randomly
      assigned to 1 of 3 conditions: 1) spouse-assisted pain-coping skills training,
      (spouse-assisted CST), 2) a conventional CST intervention with no spouse
      involvement (CST), or 3) an arthritis education-spousal support (AE-SS) control
      condition. All treatment was carried out in 10 weekly, 2-hour group sessions.
      RESULTS: Data analysis revealed that at the completion of treatment, patients in
      the spouse-assisted CST condition had significantly lower levels of pain,
      psychological disability, and pain behavior, and higher scores on measures of
      coping attempts, marital adjustment, and self-efficacy than patients in the AE-SS
      control condition. Compared to patients in the AE-SS control condition, patients
      who received CST without spouse involvement had significantly higher post
      treatment levels of self-efficacy and marital adjustment and showed a tendency
      toward lower levels of pain and psychological disability and higher scores on
      measures of coping attempts and ratings of the perceived effectiveness of pain
      coping strategies. CONCLUSION: These findings suggest that spouse-assisted CST
      has potential as a method for reducing pain and disability in OA patients.

PMID- 8997919
TI  - The use of trained patient educators with rheumatoid arthritis to teach medical
      students.
AB  - OBJECTIVE: To assess whether patients with rheumatoid arthritis (RA) trained as
      educators can enhance the integration of clinical and basic science education
      among second-year medical students during their rheumatology sequence. METHODS:
      Twenty patients with RA and strong communication skills were extensively trained
      to teach students how to perform the whole-body joint examination. Each arthritis
      educator taught three 2-hour small group sessions and participated in a
      concluding 2-hour panel discussion with the entire class. Changes in student
      knowledge and attitudes were assessed in a pre-post evaluation design. RESULTS:
      There were statistically and educationally significant gains in knowledge,
      confidence, and attitudes related to psychosocial aspects of arthritis in each of
      the 2 years the program was implemented. One-year followup data indicated
      substantial retention of these gains. CONCLUSIONS: Patients trained in arthritis
      education can effectively teach fundamental musculoskeletal examination skills
      and encourage the development of sensitivity to the impact of chronic arthritis
      on the daily life of other patients.

PMID- 8997921
TI  - Fibromyalgia syndrome: current concepts in pathophysiology, clinical features,
      and management.

PMID- 8997920
TI  - Summer camp: effects on function of children with autoimmune diseases.
AB  - OBJECTIVE: To evaluate the effects of a summer camp experience on joint range of
      motion (ROM), muscle strength, and overall function of children with autoimmune
      diseases. METHODS: Two physical therapists measured ROM and muscle strength of 44
      children pre-camp, post-camp, and at a 4-month followup clinic visit. The parents
      reported the children's functional status using the Children's Health Assessment
      Questionnaire (CHAQ) at each time period. RESULTS: Immediately after camp, all
      ROM and strength measures improved. These improvements were not maintained. The
      parents reported no functional change post-camp or at the 4-month followup clinic
      visit. There was mild correlation between the improved ROM and strength and
      eating and dressing skills (CHAQ). The effects of camp were similar for all
      children regardless of disease status or functional level. CONCLUSION: The camp
      experience affected the physical condition of children with autoimmune disease by
      temporarily improving ROM and strength, but not functional level.

PMID- 8997922
TI  - Methods for exploring curvilinear relationships and conducting tests of
      statistical significance: an illustration from orthopedic research.

PMID- 8997923
TI  - Documenting quality management in rheumatic disease: are patient questionnaires
      the best (and only) method?

PMID- 8997924
TI  - Reducing work disability associated with rheumatoid arthritis: identification of
      additional risk factors and persons likely to benefit from intervention.
AB  - OBJECTIVE: To study additional risk factors for rheumatoid arthritis (RA)-related
      work disability and to identify the groups of individuals at high risk and the
      potentially modifiable factors which place them at risk. METHODS: A cross
      sectional mail survey was conducted among 469 adults with RA. Work disability was
      defined as unemployment due to RA. A broad range of explanatory factors was
      examined, including sociodemographic, health, work, support given by others, and
      commuting difficulty. Employed and work-disabled subjects were compared by t-test
      and chi-square. Attributable fractions were calculated to assess the predictive
      value of factors. A recursive partitioning procedure identified individuals at
      varying risks for work disability, and their characteristics were defined.
      RESULTS: The risk factors joint pain and functional status, commuting difficulty,
      physical demands of the job, and disease duration were important predictors of
      work disability in both the attributable fraction and recursive partitioning
      analytic models. Having a professional or administrative job was protective,
      provided the salary earned was not low. Younger individuals with RA of shorter
      duration were placed at high risk by potentially modifiable factors. While older
      persons with RA of long duration were at high risk, modifiable factors could not
      be identified. CONCLUSION: Commuting difficulty, a previously overlooked factor,
      is an important predictor of RA work disability. Younger individuals with RA of
      relatively short duration can be placed at high risk by potentially modifiable
      factors including commuting difficulty, physically demanding jobs, greater joint
      pain and poor functional status, and nonprofessional/non-administrative jobs.

PMID- 8997925
TI  - The structure of an instrument for assessing the effects of assistive devices and
      altered working methods in women with rheumatoid arthritis.
AB  - OBJECTIVE: To use Rasch analysis to transform the ordinal score from a newly
      developed instrument, the Evaluation of Daily Activities Questionnaire (EDAQ), in
      order to obtain unidimensional linear measures; to analyze whether items change
      in difficulty with interventions; and to follow changes in subjects' degree of
      ability. METHODS: Twenty-one women with rheumatoid arthritis rated their
      perceived difficulty without and with assistive devices or altered working
      methods using the EDAQ; the EDAQ consists of 102 items of daily activities,
      divided into 11 dimensions. RESULTS: All items in the EDAQ could be structured
      into an acceptable model from "hard" to "easy" with the subjects overall measures
      ranging from "more able" to "less able." Forty-one items showed a significant
      reduction of difficulty with interventions. For some items results indicated that
      easier initial difficulty led to greater effect of interventions. In general,
      difficulty without assistive devices could not predict difficulty with
      interventions. Twenty women demonstrated a significant increase in activities of
      daily living (ADL) ability after interventions. CONCLUSION: The EDAQ analyzed
      with the Rasch model, demonstrated a hierarchical order of difficulty in 102
      items showing that it was possible to evaluate the effect of using assistive
      devices or altered working methods.

PMID- 8997926
TI  - A biopsychosocial model of disability in rheumatoid arthritis.
AB  - OBJECTIVE: To test and cross-validate a model using disease activity, pain, and
      helplessness to predict future psychological and physical disability in persons
      with rheumatoid arthritis (RA) across time. METHODS: Measures of disease
      activity, pain, helplessness, psychological function, and physical function were
      collected from 63 males with RA at baseline, 3 months, and 6 months. Path
      analytic methods were used to examine longitudinal relationships among these
      variables. RESULTS: Path analysis revealed that pain and helplessness were
      significant mediators of the relationship between disease activity and future
      disability in RA; the predictive model withstood two cross-validations.
      CONCLUSION: The findings suggest that pain and helplessness are key
      biopsychosocial variables that affect the development of disability in RA.

PMID- 8997928
TI  - Gender and ethnic differences in alternative and conventional arthritis remedy
      use among community-dwelling rural adults with arthritis.
AB  - OBJECTIVE: To examine the frequency of, and the ethnic and gender differences in,
      the use of arthritis remedies among rural adults. METHODS: Interviews were
      conducted with 219 adults from a nonmetropolitan North Carolina county.
      Participants reported whether they ever used and still used 19 remedies.
      Participants were evaluated for the actual presence of arthritis and functional
      capacity. Analysis included descriptive statistics and multivariate logistic
      regression. RESULTS: Participants used a variety of alternative and conventional
      remedies, with prayer (92%) being most widely used. Prescription medicine was
      used by 60%. Differences in remedy use included European-Americans making greater
      use of conventional remedies and African-Americans making greater use of some
      alternative remedies. Those with greater functional disability have used
      alternative remedies, but they still used prescription medicine. CONCLUSIONS:
      Rural individuals use a variety of remedies, with differences by gender,
      ethnicity, and functional capacity. Future research must examine the role of
      gender, culture, residence, and disease severity in arthritis remedy use
      decisions.

PMID- 8997927
TI  - Back pain in osteoarthritis of the knee.
AB  - OBJECTIVE: To compare patients with knee osteoarthritis (OA) who have and do not
      have back pain, and evaluate the prevalence, characteristics, and consequences of
      back pain among knee OA patients. METHODS: During a 3-year period, consecutive
      patients attending an outpatient rheumatology clinic were evaluated for the
      presence of back pain, and 368 were found to have OA of the knee. Clinical status
      was evaluated by the Clinical Health Assessment Questionnaire, radiographs, and
      joint examinations. RESULTS: Back pain was present in 54.6% of patients with OA
      of the knee. Almost every clinical status measure was worse among those reporting
      back pain, including Health Assessment Questionnaire (HAQ) disability, pain,
      global severity, fatigue, and psychological status. Back pain was more common in
      women and the obese, but was not associated with age, marital status, formal
      education, smoking history, or knee radiographic scores. In multivariate analyses
      the strongest correlates of back pain in knee OA patients were anxiety, night
      pain, HAQ disability, and global severity. CONCLUSION: Back pain is prevalent
      among OA clinic patients, more common than in rheumatoid arthritis or population
      studies, is linked to body mass index, and is associated with clinically
      significant increases in pain and other measures of clinical distress.

PMID- 8997929
TI  - Health outcome improvements in patients with systemic lupus erythematosus using
      two telephone counseling interventions.
AB  - OBJECTIVE: To examine the effectiveness of two telephone intervention strategies
      for improving the health outcomes of patients with systemic lupus erythematosus
      (SLE). METHODS: Fifty-eight SLE patients were randomly assigned to receive a 6
      month telephone counseling intervention using either a treatment counseling (TC)
      or symptom monitoring (SM) strategy. Health outcomes were assessed using the
      Fatigue Severity Scale (FSS) and the Arthritis Impact Measurement Scales 2
      (AIMS2). RESULTS: At the 6-month followup, the mean AIMS2 Physical Function scale
      and AIMS2 Social Support scale scores were significantly improved (P < 0.05) for
      the TC group compared to the SM groups. The mean FSS score, AIMS2 Affect score,
      and AIMS2 Pain score were significantly improved (P < 0.05) for both groups.
      CONCLUSIONS: Telephone interventions, especially using the TC approach, can be
      effective for improving the functional status of persons with SLE.

PMID- 8997931
TI  - Clinical quality management: putting the pieces together.

PMID- 8997930
TI  - Is consent to participate in research voluntary?

PMID- 8997932
TI  - Is it a risk factor or confounder? A discussion of selected analytic methods
      using education as an example.

PMID- 8997933
TI  - Downshifting: a new career path for nurse executives.

PMID- 8997934
TI  - Understanding one hospital's journey to shared control: a research study.

PMID- 8997935
TI  - Administrative implications of restructuring.

PMID- 8997936
TI  - Shadow and substance: values and knowledge.

PMID- 8997937
TI  - Validation of client decision-making instruments in the context of psychiatry.
AB  - We evaluated the psychometric properties of instruments measuring decisional
      conflict, decision self-efficacy, and decision emotional control with 94 clients
      diagnosed with schizophrenia who were considering the continuation of treatment
      with long-acting antipsychotic injections. The decision scales had adequate
      internal consistency (range 0.78 to 0.84) and discriminated significantly (p <
      0.000 to 0.037) between clients who expressed certainty and those who expressed
      uncertainty regarding decisions to continue with treatment. The scales may be
      useful in psychiatric populations, in identifying the factors contributing to
      difficulty in decision-making regarding treatment and evaluating decision
      supporting interventions.

PMID- 8997938
TI  - The McGill model of nursing and children with a chronic-condition: "who benefits,
      and why?".
AB  - This study sought to understand why and how the psychosocial adjustment of
      children between the ages of four and 16 with a chronic illness was improved by a
      year-long nursing trial (1990-1991), guided by the McGill Model of Nursing. We
      examined the characteristics of children whose adjustment improved (improvers),
      who remained within the normal range (adjusted), and who deteriorated (clinical
      rangers). Improvers and clinical rangers presented with similar characteristics,
      and a profile analysis was conducted to understand why one group improved while
      the other did not. Four pathways leading to improvement were identified. The
      effectiveness of the nursing appeared to be related to engagement with the nurse
      and to features of the nursing.

PMID- 8997939
TI  - Quality of life as an outcome measure in nursing research. "May you have a long
      and healthy life".
AB  - Quality of life has emerged as an important concept and outcome in health and
      health care. Policy-makers, researchers, clinicians, and the public at large
      consider perceived quality of life to be an important dimension of the health of
      a population or an individual. The nature of nursing is such that many of its
      anticipated outcomes relate to improvement in the quality of life of individuals
      and populations. There continues to be debate about the actual definition of
      quality of life, and a concept that is difficult to define will naturally pose
      challenges to measurement. This has not impeded the proliferation of quality-of
      life instruments, since the concept is recognized as an increasingly important
      clinical and research outcome. Progress has been made in clarifying and
      operationalizing the concept. We propose a conceptual viewpoint that separates
      what quality of life is from what contributes to quality of life. This will
      assist nurse researchers planning to use quality of life as an outcome in
      evaluating nursing interventions. In clinical or research situations, for the
      purposes of measurement, an operational definition of quality of life stems from
      a definition of health. From this is drawn a definition of health-related quality
      of life (HRQL). For the purpose of outcome measurement, the operational
      definition relates to the domains important to the study population and the
      particular health intervention under study. Issues that arise in the measurement
      of HRQL are also presented.

PMID- 8997940
TI  - The meta-analytic approach to research integration.
AB  - A quantitative research method for aggregating findings from empirical research,
      meta-analysis is useful for systematically integrating findings gleaned from
      individual studies. Meta-analysis goes beyond the mere summarization and critique
      of research findings, to conducting statistical analyses on the outcomes of
      similar studies. Overall, meta-analysis represents a vast improvement over
      traditional methods of research review, by providing a more thorough description
      of the current status of research in an area and a more precise estimate of the
      effects of treatments or interventions. This article describes the meta-analytic
      approach to research integration, discusses the advantages that it offers for
      integrating nursing research, and highlights some of the methodological issues
      surrounding this approach.

PMID- 8997941
TI  - Methodological issues in outcomes research.

PMID- 8997942
TI  - [Conceptual and theoretical bases of an instrument developed to identify self
      care needs in women treated for depressive disorders].
AB  - Nursing research in the field of psychiatry and mental health must be based on
      nursing models if it is to make a real contribution to the development of a body
      of knowledge specific to nursing. This article describes the conceptual
      foundations and different stages involved in the development of an instrument
      (The Self-care Needs Inventory) in the framework of a study based on the Orem
      self-care nursing model (1991, 1995). The objective of this comparative
      descriptive study was to describe self-care requisites of women treated for
      depression. The concept of self-care requisites, the fundamental aspect on which
      this research is based, refers to the expression of a general goal that
      individuals pursue or should pursue in order to maintain or improve their health
      and well-being (Orem, 1991). To study the concept and pinpoint its major
      components, we correlated the concept with intermediate-level theories: social
      adjustment of women during and after an acute depressive episode, self
      affirmation and realization, clinical manifestations of depression and how they
      are treated. These components were then made operational, i.e. measurable in
      concrete terms. A list of statements of specific self-care requisites was put
      together from various measurement tools used to evaluate identified components.
      The list was submitted to experts to establish its nominal validity. The
      instrument thus constituted was used with two groups : a group of women treated
      for depression (n = 30) and a group of women not treated for depression (n = 30).
      The women were asked to assign a value to each statement to reflect the
      importance they attached to the statement. The values were then compared to
      identify self-care requisites specific to women treated for depression.

PMID- 8997943
TI  - Frontier nursing: nursing work and training in Alberta, 1890-1905.
AB  - This article analyzes the relationship of nursing work and training from 1890 to
      1905 in that part of the North West Territory which in 1905 became the province
      of Alberta. Primary (archival) and secondary (published) data are analyzed to
      determine the nature of salaried nursing work, how nurses were recruited, the
      conditions of employment, how women were prepared for nursing work, and the
      relationship between hospital training programs and the salaried work of graduate
      nurses. Prior to 1905, most graduate nurses in Alberta were employed in
      hospitals. Their work involved administration as well as attending to patients
      and assisting physicians. Hospital boards had difficulty recruiting graduate
      nurses and began training programs to remedy their labour shortage. Programs were
      begun by the Medicine Hat General Hospital in 1894 and the Calgary General
      Hospital in 1895. Hospitals with training programs soon came to rely on pupil
      nurses for staffing. The success of these programs stimulated other Alberta
      hospitals to begin training programs, and by 1915 there were 10 programs in
      existence. Graduates of hospital programs were expected to be entrepreneurs,
      seeking employment in private practice and being reimbursed on a free-for-service
      basis by their patients. Although they were not designed to prepare nurses for
      private practice, hospital training programs did achieve some integration between
      hospital and home nursing work, partly because the primitive conditions of
      Alberta hospitals matched those of the ranches, homesteads, and even town homes.
      Pupil nurses became oriented to private duty when they were "hired out" during
      their period of training to care for ill individuals in their homes.

PMID- 8997944
TI  - Ontario Health Care Evaluation Network: building partnerships and promoting
      evidence-based practice.

PMID- 8997945
TI  - Ten years ... ten steps! 1986-1996.

PMID- 8997946
TI  - Commentary from the Capital.

PMID- 8997947
TI  - Devereaux testimony before the rate setting committee against Medicaid cuts.

PMID- 8997948
TI  - Inservice programs. The easy way!
AB  - According to adult education principles, any inservice should stimulate and
      validate staff roles as NAs. Pure lecture presentations are easily achieved in
      the churches of their choice. It is the job of the DONs to offer a variety of
      programs to NAs. This article did not explore all of the types of programs that
      could be offered to NAs, so if you have any unique programs that you have
      presented, please write a note to THE DIRECTOR, and it will be shared.

PMID- 8997949
TI  - LTC law. When executive decisions pave the road to court.

PMID- 8997950
TI  - Seeing beyond the wrinkles.

PMID- 8997951
TI  - Commentary from the Capital.

PMID- 8997952
TI  - Promoting health for the nursing home resident.

PMID- 8997953
TI  - Weight loss/malnutrition in the LTC resident ... the DON's role.

PMID- 8997955
TI  - [Variability in working systems in intensive care units].
AB  - INTRODUCTION: Patients attended in Intensive Medicine Services (IMS) require a
      high therapeutic support. To do so, each IMS elaborates a work system (monitoring
      of constants, insertion of catheters,...) aiming to respond to these high
      necessities of therapy. The objective of this study is to describe the
      variability among different IMS. METHODS: The study was performed in 15 hospitals
      in Catalonia between April and May 1995. In the end two of them did not
      participate in the study. In each hospital 180 pieces of data were collected
      referring to their material and human resources, graphics of data collection,
      monitoring of respiratory system (mechanical ventilator, aspirations of
      secretions, tracheostomy care), techniques of catheterization of artery and
      venous via vesical probing, prevention of pressure ulcers , hygiene of patients,
      nutrition, family treatment and data about medical orders and nursing courses.
      Similarly, the fact whether the work system was justified by studies from the
      same IMS, other centres, or whether it was simply unknown, was also evaluated.
      RESULTS: There was a great variability among the IMS studied, oscillating
      significatively according to assigned resources, frequency of action and cost.
      According to the procedure 61% of IMS did not justify the work systems depending
      on scientific data. CONCLUSION: it is necessary to unify the different work
      systems. To do so, and in our opinion, scientific societies should establish
      common norms, guidelines and protocols so as to obtain a higher efficiency of
      IMS.

PMID- 8997954
TI  - [Factors causing stress in patients in intensive care units].
AB  - Intensive care units have been considered stress generating areas. Knowing the
      causes why this happens will allow us to take specific measures to prevent or
      minimize it. This study has been performed with the aim to identify stress
      raising factors, as they are perceived by intensive care patients. The study has
      been performed in 49 patients most of whom were being attended in postoperatory
      control. The valuation of the degree of stress was performed using the "Scale of
      Environmental Stressors in Intensive Care" by Ballard in 1981, modified and
      adapted to our environment, with a result of 43 items distributed in six groups;
      Immobilization, Isolation, Deprivation of sleep, Time-spacial disorientation,
      Sensorial deprivation and overestimulation, and depersonalization and loss of
      autocontrol. The level of stress perceived by patients was low. The factors
      considered as most stressing were those related to physical aspects; presence of
      tubes in nose and mouth, impossibility to sleep and presence of noise, whereas
      those less stressing referred to Nursing attention. We conclude that patients
      perceive ICU as a little stressing place in spite of the excessive noise, remark
      the presence of invasive tubes and the difficulty to sleep as the most stressing
      factors, and in the same way, express a high degree of satisfaction about the
      attention received.

PMID- 8997956
TI  - [Incidence of pneumonia due to mechanical ventilators in relation to external
      circuit changes in the respirator].
AB  - Pneumonia is one of the infections of highest relevancy in Intensive Care Units,
      and according to the incidence of pneumonia associated to mechanical ventilation,
      the frequence of the ventilator external circuits change is still a topic of
      discussion. We decided to modify the protocol of change in our unit, from doing
      it every 48 hours to every 7 days. We performed a prospective study in 108
      patients attended in a Polyvalent ICU who underwent mechanical ventilation during
      more than 24 hours. We formed two groups, in Group 1 we changed circuits every 48
      hours and in Group 2 the circuits were changed every 7 days, without using
      bacterian filters in any of the groups. The results obtained in Group 1 were of
      an accumulated incidence of pneumonia associated to mechanical ventilation of 18%
      and density of incidence of 21.1 pneumonias per 1000 days of mechanical
      ventilation. In Group 2 we obtained an accumulated incidence of pneumonia
      associated to mechanical ventilation of 19% and a density of incidence of 20.5
      pneumonias per 1000 days of mechanical ventilation. In the analysis of data there
      were no significant statistic differences between both groups. The cost of
      respirator external circuits was diminished in 27% in Group 2. We conclude that
      the circuits change every 7 days does not produce an increase in the frequence of
      pneumonia associated to mechanical ventilation, with the expense of the
      respirator external circuits being remarkably reduced.

PMID- 8997957
TI  - [Estimation of a confidence interval of a mean and a proportion].

PMID- 8997959
TI  - Nursing "mergers".

PMID- 8997958
TI  - [Description of the intensive care unit of the Castellon General Hospital].

PMID- 8997960
TI  - Diphenhydramine hydrochloride helps symptoms of ciguatera fish poisoning.

PMID- 8997961
TI  - A look back: medieval medicine.

PMID- 8997962
TI  - Pepper spray exposure during a carjacking attempt.

PMID- 8997963
TI  - Attitudes of emergency nurses toward organ and tissue donation.
AB  - OBJECTIVE: Organ and tissue transplantation has gained increased acceptance as a
      medical procedure. Costs for most transplantations are reimbursed by insurance
      companies, and the list of transplantable tissues and organs has doubled during
      the past 10 years. To meet this resulting increased demand, more organs and
      tissues need to be recovered from potential donors. The purpose of this study was
      to examine the relationship between emergency nurses' attitudes and their
      intention to ask potential donor families if they will donate their family
      member's organs and tissues. METHODS: Thirty hospitals were sent a letter
      inviting them to participate in this descriptive survey research design. Survey
      packets were sent to the 17 hospitals that responded positively to the request.
      Surveys contained a cover letter to the participants with directions and
      assurance that anonymity would be maintained. Completed surveys were returned
      directly to the researcher. RESULTS: We found a relationship between the nurses'
      attitudes and the frequency with which they approached families regarding
      donation. Further analysis revealed that nurses' attitudes about organ and tissue
      donation were related to their confidence in asking families about donation. The
      study also demonstrated that emergency nurses want educational programs that
      offer information on how to approach donor families. DISCUSSION: These results
      can be used to develop educational programs for emergency nurses to provide them
      information that can increase their confidence in asking families about donation
      and subsequently increase the number of families they approach regarding
      donation.

PMID- 8997964
TI  - The effect of in-service education on emergency nurses' documentation of physical
      assessment.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of a staff
      education program on the documentation skills of registered nurses in the
      emergency department. DESIGN: A quasiexperimental posttest design was used in
      this project. METHODS: We conducted classes based on the Emergency Nurses
      Association's (ENA) Core Curriculum and focused on documentation of neurologic,
      abdominal, pulmonary, and cardiac assessments. Twenty emergency nurses attended
      the classes. ED charts were reviewed according to ENA assessment priorities
      criteria 3 months after the class. Two hundred ED charts completed by registered
      nurses who attended the classes were compared with 200 ED charts completed by a
      comparison group of 20 registered nurses who did not attend the classes. RESULTS:
      Treatment group registered nurses documented significantly more of the ENA
      criteria in each system area than did the registered nurses in the comparison
      group. CONCLUSION: Findings from this study support the importance of continued
      staff education in the improvement of emergency nurses' documentation of patient
      assessment.

PMID- 8997965
TI  - A comparison of aural and rectal temperature measurements in children with
      moderate and severe injuries.
AB  - OBJECTIVE: The purpose of this study was to compare initial rectal and aural
      (i.e., ear-based) temperature measurements in children with moderate and severe
      injuries during their trauma care in the emergency department. DESIGN: A cross
      sectional, prospective design was used to compare aural temperature and rectal
      temperatures in injured children. SAMPLE/SETTING: A convenience sample of 40
      children who met the study inclusion criteria were enrolled at the level I
      pediatric regional resource trauma center in western Pennsylvania. METHODS: Aural
      temperature was measured by infrared technology (IVAC Corporation, San Diego,
      Calif.), and rectal temperatures were measured with a thermistor (IVAC
      Corporation). RESULTS: The subjects (N = 40) ranged in age from 1 to 14 years
      (mean 6.9 years; SD = 4.4 years). The mean difference between rectal and aural
      temperature measurements (mean = -0.3 degree C; SD = 0.76 degree C) was
      statistically significant when compared with a paired t test (p < 0.05). The
      Pearson product-moment correlation coefficient between aural and rectal
      temperature measurements was moderate to high (r = 0.85). CONCLUSION: The
      moderate to high correlation between the two methods shows promise for use of
      aural infrared temperature measurements as a screening measure for children with
      moderate and severe injuries.

PMID- 8997966
TI  - Telephone advice: lessons learned and considerations for starting programs.

PMID- 8997968
TI  - A SANE experience in a community hospital: Doylestown's first six months.

PMID- 8997969
TI  - Volunteer patient advocates in the emergency department.

PMID- 8997967
TI  - Troubleshooting central venous catheters in the emergency department.

PMID- 8997970
TI  - Lessons learned from a cold weather miracle.

PMID- 8997971
TI  - Using data to discover new patterns: a triage quality indicator.

PMID- 8997972
TI  - Pocket guide to ED orientation.

PMID- 8997973
TI  - Teaching tools for heart failure.

PMID- 8997974
TI  - A five-year-old boy with hematemesis.

PMID- 8997975
TI  - Getting your study funded: tips for new researchers.

PMID- 8997976
TI  - Sexual assault nurse examiner (SANE) programs.

PMID- 8997977
TI  - Weather-related trauma: an unusual case of penetrating abdominal injury.

PMID- 8997978
TI  - An unconscious adult man with apparent alcohol intoxication.

PMID- 8997979
TI  - Coming out of the closet: a nurse with obsessive-compulsive disorder tells her
      story.

PMID- 8997980
TI  - Life after life and who has my glasses?

PMID- 8997981
TI  - Formula for ED staffing.

PMID- 8997982
TI  - The Tao, social constructionism and psychiatric nursing practice and research.
AB  - For the reader who is more accustomed to the standard form of academic papers, it
      seemed necessary to prepare the ground for a more discursive presentation that
      does not follow the conventions of, for example, using the third person or
      summarizing the paper initially. If conventions are simply customs agreed amongst
      people then the academic 'form' can be put in parentheses for this paper, for
      this journal, for...?-'...Scholarly Dissertations contain no more of the
      character of Taoist wisdom than does the typical wax museum' (Hoff 1982, p. 26).

PMID- 8997983
TI  - Live supervision and family systems nursing: postmodern influences and dilemmas.
AB  - Evolving nursing practices in a graduate nursing education programme that offers
      live clinical supervision in family systems nursing can be conceptualized within
      a postmodern perspective. Postmodernism is described as a debate about knowledge
      that questions traditional foundational theories or explanations in science,
      culture, religion and literature. Practices of a clinical supervision system,
      i.e. a graduate student, supervisor, and clinical team, illustrate postmodern
      influences on clinical work with families. Dilemmas posed by contemporaneity of
      modern and postmodern influences are also explored.

PMID- 8997984
TI  - Chaos and the way of Zen: psychiatric nursing and the 'uncertainty principle'.
AB  - The biological sciences have been dominated by 'classicist' science-predicated on
      the post-Enlightenment belief that a real world exists, which behaves according
      to notions of causality and consistency. Although medicine, and by implication
      psychiatric nursing, derives its explanatory power from such a science, much of
      its focus-illness-is not amenable to causal explanation or prediction. The
      theoretical developments of the 'new physics' have been used to redefine science
      and, as a result, have challenged traditional constructions of reality. The new
      physics are usually framed in terms of the physical world, or to construe
      consciousness. In this paper I shall consider the implications of chaos-a
      relative of the new physics-for psychiatric nursing practice. As nursing appears
      to crave a 'certainty principle' to govern the theoretical underpinnings of
      practice, this study considers how chaos might contribute to a metaparadigm of
      nursing.

PMID- 8997985
TI  - The human factor.
AB  - Defining the core activity of psychiatric nursing is helpful if the discipline
      seeks professionalization. A definition offers a sense of stability within the
      current culture of change in care provision. However, core activity may be
      incongruent with postmodern ideas and practice. The paper attempts to square this
      circle. It addresses the complexity of describing core activity when this is
      based on implicit knowledge of practice, based in art rather than science. Using
      a phenomenological research approach, the research involved encouraging
      psychiatric nurses within residential schemes to consider the meaning of their
      concrete activity. Initial findings suggest that the core activity is working
      with extraordinary people within 'ordinary' relationships, and in 'ordinary'
      contexts.

PMID- 8997986
TI  - Economies with 'the truth': professionals' narratives about lying and deception
      in mental health practice.
AB  - In psychiatric and psychotherapeutic literature, the idea of clients lying is not
      one that is commonly voiced, and many therapeutic positions seem to discourage
      discussion of the issue. In practice, however, professionals do meet with people
      who they feel are not being 'truthful', and this study sought to examine the
      narratives that a group of colleagues provided about the resulting conflicts and
      dilemmas. Through the use of unstructured interviews, I invited mental health
      practitioners to discuss their experiences of situations where they felt clients
      were lying to them. From an analysis of these research conversations I propose
      that, in a psychiatric context, lying and secrecy often occur as response to an
      experience of powerlessness by service-users. I also suggest that the issue of
      clients lying requires more open discussion amongst practitioners, in order to
      explore differences in power and perspective between professionals and clients.

PMID- 8997987
TI  - The last post? Defending nursing against the postmodernist maze.
AB  - Is postmodernism in many ways the empiricist-liberal tradition at the inevitable
      end of its intellectual and political tether? Or is postmodernism the 'laughter
      of genius' that art and argument in their traditional forms are dead? Can
      postmodernism be applied to social and economic issues whilst carrying a denial
      of the manner by which Western thought has shaped these issues? Can postmodernism
      provide moral pathways to help us with contemporary ethical issues? How can
      postmodernist thought encompass the activities of nurses, particularly in the
      area of psychiatric care? Can nurses afford postmodernist suppositions in the
      face of suffering and pain? If postmodernism exists, does it exist everywhere (as
      does nursing) or is it a more localized event?

PMID- 8997988
TI  - Problems of the researching person: doing insider research with your peer group.

PMID- 8997989
TI  - Using a reflexive diary in social constructionist research into clinical
      practice.

PMID- 8997990
TI  - From modernism to postmodernism: the implications for nurse therapist
      interventions.

PMID- 8997991
TI  - The SMI nurse.

PMID- 8997992
TI  - Challenging 'the institution'.

PMID- 8997993
TI  - Postmodernism.

PMID- 8997994
TI  - [Support of the parents during the care of newborns and premature infants].

PMID- 8997996
TI  - [Skin disorders in the newborn].

PMID- 8997995
TI  - [Nursing standard "Mouth care"].

PMID- 8997997
TI  - [The concept of rehabilitation at the Bad Oexen children's home].

PMID- 8997998
TI  - [Effect of family-oriented rehabilitation on the quality of life--results of an
      evaluation study].

PMID- 8997999
TI  - [Breast feeding--from a sociological viewpoint. 1. Introductory considerations on
      infant nutrition in changing times and on the advantages of breast feeding].

PMID- 8998000
TI  - [Award of the Antonie Zerwer Medal on the occasion of the 18. Congress for
      Pediatric Nurses, September 12 to 14, 1996 in LubbeckInterview by Andreas Kray].

PMID- 8998001
TI  - [About the quiet little place].

PMID- 8998002
TI  - [The Norton scale as an instrument for the prevention of decubitus ulcers within
      the framework of quality assurance. Familiarity and acceptance--possible
      consequences for practice instruction].

PMID- 8998003
TI  - [Endoscopic standards reached in plastic and reconstructive surgery].

PMID- 8998004
TI  - [New at intensive care units: effective prevention of respiratory complications
      with Pulmo-Dyn].

PMID- 8998005
TI  - [Threat of punishment in nursing a security risk?].

PMID- 8998006
TI  - [The quality of nursing administration].

PMID- 8998008
TI  - [Diakonism wanting to be humanity's champion].

PMID- 8998007
TI  - [Environmental management in the hospital].

PMID- 8998009
TI  - [Just a handful of life, but a whole person].

PMID- 8998010
TI  - [Remember the forgotten patients in pain].

PMID- 8998011
TI  - [Stress management. The contribution of self help groups].

PMID- 8998012
TI  - [From education to employment. The first results are conclusive].

PMID- 8998013
TI  - [The bet].

PMID- 8998015
TI  - [Rising cost of health insurance. How communities and cantons can earn for
      themselves].

PMID- 8998014
TI  - [New increase in health insurance premiums. A way to escape the premium hammer].

PMID- 8998016
TI  - [Visiting the patient in his home "... so that you can go home sooner"].

PMID- 8998017
TI  - [General armament. Nursing has to be part of it. Interview by Fred Arm].

PMID- 8998018
TI  - [Federal elections on the 1. December. "No" to the revision of labor
      legislation].

PMID- 8998019
TI  - On missions and markets: continuity and change.

PMID- 8998020
TI  - An interview with Joanne Disch. Interview by Connie R. Curran.
AB  - Joanne Disch, PhD, RN, FAAN, is senior associate director and director of patient
      family services at the University of Minnesota Hospital and Clinic (UMHC). In
      this interview, she discusses patient care system redesign and UMHC's, and the
      nursing staff's, development and evolution in a Stage 4 managed care market.

PMID- 8998021
TI  - Quality and cost outcomes of transitional care.
AB  - Longitudinal analysis of the outcomes of a transitional care program documented
      success in discharging patients home with remarkable compliance to discharge
      plans and sustained improvement in mental status and functional independence.
      Inpatient costs were significantly reduced.

PMID- 8998023
TI  - A cost estimation model for measuring professional practice.
AB  - A cost estimation model was developed to monitor the effect of an enhanced
      professional practice model on cost to the institution. The model detected
      differences across units and changes in unit activities. One unit's cost savings
      were greater than the others and this difference was believed to be related to
      stable leadership over the course of the study.

PMID- 8998022
TI  - Partners in patient care: measuring the effects on patient satisfaction and other
      quality indicators.
AB  - An experimental pretest/posttest design compared pilot and control nursing units
      in a medical center in Southwest Florida to assess the effects of a Partners in
      Patient Care (PIPC) nursing care delivery model on selected quality of care
      outcomes-patient satisfaction, patient medication errors, falls, and IV
      infections. There were no significant differences between units in the number of
      falls, medication errors, and IV infections. When the ratios of these events to
      patient days were examined, there was a significant difference between the pilot
      and control units in the medication error ratio and the fall ratio. The results
      indicate that the PIPC nursing model had a positive effect on patient
      satisfaction.

PMID- 8998024
TI  - Economic awareness of nurses: relationship to budgetary control.
AB  - Cost savings, a goal in most health care settings, could be achieved by
      strategies leading to greater economic awareness. Nurse manager participation in
      budgeting, staff nurse awareness, and costs relative to linen and supply use were
      evaluated in this study. Staff who are aware of and use information about the
      relationship between their clinical behavior and cost savings could make a major
      impact on the financial health of their units.

PMID- 8998025
TI  - Issues of access: what is going on in health care?
AB  - Our nation spends more per capita on health care than any other nation, yet there
      are still approximately 37 million Americans without health insurance. Why has
      this happened? What are some barriers that prevent Americans from attaining
      access to adequate health care?

PMID- 8998026
TI  - A model for case management of high cost Medicaid users.
AB  - The material presented reveals a unique solution to meeting the health care needs
      of a certain population. The State of Maryland through the Maryland Medicaid High
      Cost User Initiative uses nursing case management to decrease costs while
      providing quality care. The Center for Health Program Development and Management
      (CHPDM) manages the program and will be providing "enhanced" case management
      services to the identified high-cost users under the age of 65.

PMID- 8998027
TI  - The real truth about taxes and health care spending.

PMID- 8998028
TI  - What's new? What's different?: a collaborative accreditation survey.

PMID- 8998029
TI  - On Leadership. The change leader.

PMID- 8998030
TI  - Burnout: is it happening to you? And what to do?

PMID- 8998031
TI  - Resolving the ethical dilemma of nurse managers over chemically-dependent
      colleagues.
AB  - This paper addresses the nurse manager's role regarding chemically-dependent
      nurses in the workplace. The manager may intervene by: terminating the contract
      of the impaired colleague; notifying a disciplinary committee; consulting with a
      counselling committee; or referring the impaired nurse to an employee assistance
      programme. A dilemma may arise about which of these interventions is ethically
      the best. The ethical theories relevant to nursing involve ethical relativism,
      utilitarianism, Kantian ethics, Kohlberg's justice, and Gilligan's ethic of care.
      Nurse managers first need to understand these theories in order to clarify their
      own perceptions and attitudes towards chemical dependency, and then
      satisfactorily resolve this ethical dilemma. Education and social learning are
      routes to a better understanding of chemical dependency and to broadening the
      ethical dimensions of nurse managers.

PMID- 8998032
TI  - Ethical dilemmas experienced by hospital and community nurses: an Israeli survey.
AB  - The objective of this survey was to assess the extent to which nurses encounter
      and identify dilemma-generating situations in the light of the publication and
      circulation of the Israeli code of ethics for nurses in 1994. The results are
      being used as a basis for a programme aimed at promoting nurses' decision-making
      skills in coping with ethical dilemmas. In this era of major advances in
      medicine, the nurse's role as the protector of patient rights may bring about
      conflicts with physicians' orders, with institutional policies, or with patients'
      families. Nurses will then become confronted with ethical and moral dilemmas. A
      nationwide survey was carried out to identify and describe the ethical conflicts
      with which nurses in Israel are confronted in the course of their work. A third
      of the enumerated dilemmas were encountered by more than 50% of the nurses. The
      major determinant influencing encounters with dilemmas, as perceived by the
      participating nurses, was their work setting, namely, the hospital versus the
      community. It was shown that nurses seek support mainly among their peers, they
      are barely familiar with the Israeli Code, and they consider their own families
      as the predominant factor in shaping their ethical attitudes.

PMID- 8998033
TI  - Dehydration among terminally ill patients: an integrated ethical and practical
      approach for caregivers.
AB  - The purpose of this paper is to examine the possibilities and limitations of an
      ethical and practical approach to terminal dehydration. We have argued that
      dehydration among terminally ill patients offers an important key to a better
      understanding of the dying process, and that the caregivers' reactions can lead
      to a deepening of holistic palliative care. This article makes clear that the
      moral question of terminal dehydration can only be treated by an
      interdisciplinary approach. Therefore, before studying the question of the most
      humane course possible, we must first understand the meaning of dehydration and
      its repercussions for the dying patient. Inspired by an attitude of respect for a
      good dying process, we have suggested that it is possible to put forward as a
      general guideline that medical therapy should be progressively reduced when it
      has been determined that a patient has reached the terminal stage, or is in an
      irreversible deteriorating process. We describe the critical somatic, social,
      psychological, moral and spiritual points, which make up an ethical approach to
      terminal dehydration (TD). In the total care of the irreversibly terminally ill
      patient, tolerating TD can be an expression of an authentic and caring
      involvement in the dying patient's welfare.

PMID- 8998034
TI  - The ethical arguments concerning the artificial ventilation of patients with
      motor neurone disease.
AB  - This paper focuses on the ethical dilemmas created by advanced technology that
      would allow patients with motor neurone disease to be sustained by artificial
      ventilation. The author attempts to support the patient's right to informed
      choice, arguing from the perspective of autonomy as a first order principle. The
      counter arguments of caregiver burden and financial restraints are analysed. In
      the UK, where active euthanasia is not legalized, the dilemma of commencing
      ventilation is seen to be outweighed by the problems of withdrawing this
      treatment. The lack of accurate data and protocols that would clarify the current
      situation is emphasized and the conclusion takes the form of a recommendation for
      further research.

PMID- 8998035
TI  - Self-determination in clinical practice: the psychiatric patient's point of view.
AB  - This article looks at the relevance of the concept of self-determination to
      psychiatric patients by studying the existence, importance and manifestations of
      self-determination. The data were collected by interviewing long-term patients (n
      = 72) in one mental health care organization, which included a psychiatric
      hospital and an outpatient department. Self-determination was defined in terms of
      the right to decision-making, the right to information, the right of consent, the
      right to refuse treatment, and the right to be heard and taken into account. It
      was found that, with the exception of the right to refuse and consent, these
      rights are indeed present in the practice of psychiatric nursing and that they
      are relevant, and important to psychiatric patients. The patients typically gave
      ethical practical and legal reasons for a psychiatric patient's right to self
      determination. The main reasons why psychiatric patients said they lacked the
      right to self-determination were illness and staff authority. Recommendations for
      educational, clinical and methodological implications for the future in nursing
      are discussed.

PMID- 8998036
TI  - Policy options for a regulatory body for nursing in South Africa.
AB  - This article describes the use of a Policy Delphi to explore the options for
      restructuring the regulatory body for nursing in South Africa. Two rounds using
      postal questionnaires were used, the second of which also included group
      interviews. Aspects such as the statutory home of the body, its structure, who
      should appoint or elect members, and its composition, were explored. To a large
      extent, there was agreement on many issues. It would seem that this approach to
      consulting the profession is a profitable one, which informs while it consults.

PMID- 8998037
TI  - Euthanasia: towards a European consensus?

PMID- 8998038
TI  - The immorality of preregistration nurse education: a personal perspective.

PMID- 8998039
TI  - What is nursing research.

PMID- 8998040
TI  - Loving home care for the elderly.

PMID- 8998041
TI  - T.N.A.I.: my expectations.

PMID- 8998042
TI  - Nurses' Day at Rashtrapati Bhavan.

PMID- 8998043
TI  - A new hope for schizophrenics: efficacy of a new drug.

PMID- 8998045
TI  - Confusion reigns over nurse practitioners.

PMID- 8998044
TI  - Myths on the rocks: uses and abuses of alcohol (continuing education credit).

PMID- 8998046
TI  - Hard times ahead.

PMID- 8998047
TI  - Still alight.

PMID- 8998048
TI  - A little care can go a long way.

PMID- 8998049
TI  - Coming to terms with grief. Interview by Daniel Allen.

PMID- 8998050
TI  - Facing the future.

PMID- 8998051
TI  - Missing the target.

PMID- 8998052
TI  - An evaluation of mechanical aids used within the NHS.
AB  - This paper describes Phase III of the study of mechanical aids used within the
      NHS, the aim of which was to evaluate the acceptability and effectiveness of
      mechanical aids within the service. Phases I and II of the study consisted of
      interviewing nurses and clients concerning their attitudes towards mechanical
      aids and observing nurses in the clinical area using mechanical aids. Phase III
      consisted of an experiment being undertaken to compare the usability of a number
      of mechanical aids for controlled task in a laboratory environment. The aim of
      this was to compare a number of different mechanical aids currently available,
      for perceived safety, comfort, ease of use and manoeuvrability in ward simulated
      conditions.

PMID- 8998053
TI  - Guidelines on conducting a critical research evaluation.

PMID- 8998054
TI  - Ventilator tubing change times and the infection control nurse.
AB  - In line with the dramatic revolution in healthcare delivery within the last
      decade, the role of the infection control nurse (ICN) as first described by
      Brendan Moore (1959) must change to meet today's expectations. This article
      suggests that ICNs should function as clinical nurse specialists (CNS). The
      author shows how this change in role can be used to implement research-based
      practice by using the example of changing ventilator tubing change times.

PMID- 8998055
TI  - Tissue viability. Healing cavity wounds with negative pressure.

PMID- 8998056
TI  - Tissue viability. Treating leg ulcers with high pressure irrigation devices.

PMID- 8998057
TI  - Tissue viability. Superficial partial thickness burns of the hands.

PMID- 8998058
TI  - Nurses can be partners with GPs under new law.

PMID- 8998059
TI  - On the scrap-heap.

PMID- 8998060
TI  - Home economics.

PMID- 8998062
TI  - Great expectations. Interview by Pat Healy.

PMID- 8998061
TI  - Bumpy road to success.

PMID- 8998063
TI  - Leading by example. Interview by Charlotte Alderman.

PMID- 8998064
TI  - Reflection for action: the challenge for nurses.
AB  - In June, The Foundation of Nursing Studies (FoNS) launched its first position
      paper, Reflection for Action. This report highlights the key aims of the paper
      which were to explore national and local research implementation cultures, and to
      identify barriers, expectations, achievements and opportunities for the future.

PMID- 8998065
TI  - Expanding career options.
AB  - The changing nature of today's employment environment means that nurses must be
      prepared to develop within roles and through lateral career moves. To coincide
      with the establishment of the Health Care Practice Research Centre at the
      University of Northumberland, this report describes the innovative approaches to
      career management being developed there.

PMID- 8998067
TI  - Understanding asthma (continuing education credit).

PMID- 8998066
TI  - A study into clients' attitudes towards mechanical aids.
AB  - In the second article of three (the first appeared in last week's issue), the
      authors describe Phase II of the study "An Evaluation of Mechanical Aids used
      within the NHS', the aim of which was to evaluate the acceptability and
      effectiveness of mechanical aids. In this article clients' attitudes toward
      mechanical aid use is considered. This is supplemented by data obtained through
      observing nurses and clients using mechanical aids in the clinical area. It was
      found that, although mechanical aids were considered desirable and safe by most
      patients and their operation involved only moderate postural discomfort to the
      nurses operating them, the nurses still offered client discomfort or fear as a
      reason for not using the aids. The authors offer some recommendations to
      encourage increased use of mechanical aids in appropriate client care situations.
      The final article, describing Phase III of the study, will appear in next week's
      issue.

PMID- 8998069
TI  - Cardiology. Transluminal aortic stenting.

PMID- 8998068
TI  - Cardiology. Cardiomyoplasty.
AB  - Cardiac transplantation is an excellent surgical option that offers positive
      results for many patients with end stage heart failure (Large 1995). However, the
      availability of donor hearts does not meet the demand, resulting in the exclusion
      of patients who, for example, are more than 60 years old and for whom
      transplantation is contraindicated. Dynamic cardiomyoplasty has been developed to
      help such a client group.

PMID- 8998070
TI  - Cardiology. Minimally invasive cardiac surgery (MICS).
AB  - Minimally invasive cardiac surgery (MICS) has been described by some surgeons as
      a quantum leap forward which could soon replace some forms of traditional
      surgery. Sally Glennen and Helen Metcalfe describe the procedure and nursing care
      involved.

PMID- 8998071
TI  - Cardiology. Managing equipment.
AB  - As nurses have become involved in more and more highly technological procedures
      and with the risk of possible litigation associated with potential cross
      contamination from the reuse of disposable equipment, the management and safe use
      of equipment are playing an increasingly important role in all spheres of
      cardiology and cardiac care.

PMID- 8998073
TI  - Absence of p53 mutations in malignant mesotheliomas.
AB  - Mutations in the p53 gene are the most common genetic alterations found in human
      malignancies. In this study, a search was done for mutations in the conserved
      regions of the p53 gene in malignant mesotheliomas. Thirteen malignant
      mesotheliomas collected over the preceding 12 yr and maintained in paraffin
      blocks were examined by polymerase chain reaction (PCR) followed by both single
      strand conformation polymorphism (SSCP) and denaturing gradient-gel
      electrophoresis (DGGE). Direct sequence analysis was performed in cases suspected
      for mutations. No mutations in exons 5 to 8 of the p53 gene were detected. Our
      results suggest that malignant transformation of human mesothelioma cells does
      not require inactivation of p53 by point mutations in the conserved regions of
      the gene.

PMID- 8998072
TI  - Bronchial mucosal expression of the genes encoding chemokines RANTES and MCP-3 in
      symptomatic atopic and nonatopic asthmatics: relationship to the eosinophil
      active cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating
      factor, and IL-3.
AB  - Intrinsic (nonatopic) asthma is considered to be a distinct pathogenetic variant
      of asthma since, unlike extrinsic (atopic) asthma, patients are skin-prick test
      negative to common aeroallergens and have total serum immunoglobulin E
      concentrations within the normal range. However both atopic and nonatopic asthma
      are characterized by chronic inflammation of the bronchial mucosa in which
      eosinophils are prominent and are believed to be associated with local tissue
      damage. Therefore, specific eosinophil chemoattractants acting in concert with
      factors which prolong eosinophil survival may at least partly account for
      selective eosinophil recruitment to the asthmatic bronchial mucosa. The CC
      chemokines RANTES and monocyte chemotactic protein 3 (MCP-3) are potent
      eosinophil chemotactic factors, while the cytokines interleukin (IL)-5,
      granulocyte macrophage-colony-stimulating factor (GM-CSF), and IL-3 prolong
      eosinophil survival. We have tested the hypothesis that elevated numbers of cells
      expressing mRNA for RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3 are
      present in bronchial biopsies from atopic and nonatopic asthmatics compared with
      atopic and nonatopic nonasthmatic controls. The technique of in situ
      hybridization using 35S-labeled riboprobes was employed to detect mRNA+ bronchial
      mucosal cells. Compared with controls we observed significant increases in the
      numbers of cells expressing RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3
      (all P values < 0.001) in atopic and nonatopic asthmatics. These observations
      support the view that atopic and nonatopic asthma are associated with combined
      bronchial mucosal expression of CC chemokines (RANTES and MCP-3), together with
      eosinophil-active cytokines (IL-5, GM-CSF, and IL-3). These cytokines might
      contribute to the bronchial mucosal accumulation of activated eosinophils in both
      atopic and nonatopic variants of asthma.

PMID- 8998074
TI  - Expression of CD44 isoforms is increased in the airway epithelium of asthmatic
      subjects.
AB  - Since shedding of columnar, but not basal, epithelial cells is common in asthma,
      cell adhesion molecules such as CD44, which are differentially expressed on these
      cell types, are likely to be important in this disease. In bronchial epithelium
      of asthmatic and nonasthmatic subjects, CD44 isoforms have been localized by
      light- and electron-microscopic immunocytochemistry. Immunoreactivity for total
      CD44 (mAb Hermes-3/mAb 25.32) and for isoforms containing CD44v9 (mAb 11.24),
      CD44v6 (mAb 11.9), and CD44v4 (mAb 11.10) have been compared. In nonasthmatic
      samples, CD44s and CD44v9 were seen on basal but not columnar epithelial cells.
      Weak CD44v6 immunoreactivity was found infrequently in the bronchus, whereas
      CD44v4 immunoreactivity was absent. This indicates the presence of a distinct
      population of basal cells that express CD44. No CD44 was detected in areas of
      close cell-cell or cell-matrix contact, thus precluding the involvement of CD44
      in stable adhesion in these areas. CD44 immunoreactivity was locally increased in
      areas showing morphologic damage to the epithelium. In epithelium from asthmatic
      subjects, the mean level of CD44 immunoreactivity on basal-cell membranes was
      doubled (4.3 versus 2.0 gold particles/microns membrane) as compared with
      nonasthmatic subjects. Increased expression of CD44 in asthmatic subjects,
      suggests that it has a significant role in the pathobiology of this disease,
      whereas the restricted distribution of this increase supports an association with
      repair rather than with inflammatory processes.

PMID- 8998075
TI  - Adenovirus E1A gene dysregulates ICAM-1 expression in transformed pulmonary
      epithelial cells.
AB  - Previous studies from our laboratory demonstrated that adenovirus E1A DNA and
      proteins are detected in lungs of patients with chronic obstructive pulmonary
      disease (COPD). Since adenovirus E1A gene products are known to regulate the
      expression of many genes by interacting with cellular transcription factors, we
      postulate that E1A enhances the production of inflammatory mediators and
      exacerbates the inflammatory process in smokers' lungs. To examine this
      possibility, we transfected A549 human pulmonary epithelial cells with a plasmid
      carrying the adenoviral E1A gene and isolated stable transfectants expressing E1A
      proteins. These E1A-producing clones were tested for intercellular adhesion
      molecule-1 (ICAM-1) expression. As compared with parental cells or cells
      transfected with control plasmid, ICAM-1 expression was suppressed after IFN
      gamma stimulation but markedly increased by LPS stimulation of E1A-positive
      cells. This LPS-mediated ICAM-1 induction was serum-dependent but the LPS
      receptor, CD14, was not detected on the surface of the E1A transfectants. We
      conclude that E1A proteins modulate ICAM-1 induction by inflammatory stimuli and
      render lung epithelial cells sensitive to LPS, and suggest that dysregulation of
      inflammatory mediator expression by adenoviral E1A could amplify the inflammatory
      process present in airways of smokers to produce COPD.

PMID- 8998076
TI  - Cytomegalovirus modulates transcription factors necessary for the activation of
      the tumor necrosis factor-alpha promoter.
AB  - Several studies have demonstrated that cytomegalovirus (CMV) infection increases
      expression of the tumor necrosis factor (TNF) gene. This effect is mediated, in
      part, by an effect of the CMV immediate early 1 (IE1) gene product on the TNF
      promoter. To further analyze these interactions, we used plasmids with TNF
      promoter truncations to determine the site within the promoter where the CMV IE1
      gene product mediates its effect. The site was localized to a 40-base pair
      segment that contains a cAMP response element (CREB). Deletion of the cAMP
      response element increased basal promoter activation but had little effect on IE1
      induced activation. Additional studies demonstrated that the cAMP element is
      flanked 5' by a PU.1 site and 3' by an NF-kappa B site, both of which increase
      expression of the TNF promoter. These sequences demonstrated IE1 responsiveness.
      We next determined the relevance of these observations for normal human cells by
      infecting human alveolar macrophages with CMV. In these studies we evaluated
      expression of NF-kappa B, PU.1 and CREB by gel shift assay at immediate early
      times after infection. We found that CMV infection increased the binding activity
      of NF-kappa B and PU.1 and decreased the binding activity of CREB. CMV infection
      also increased expression of the TNF gene in alveolar macrophages. These
      observations suggest that CMV increases TNF gene expression, in part, by altering
      the binding activity of transcription factors that regulate gene expression.

PMID- 8998077
TI  - Antigen receptor-stimulated peripheral blood and bronchoalveolar lavage-derived T
      cells induce MHC class II and ICAM-1 expression on human airway smooth muscle.
AB  - The current model of lymphocyte extravasation into areas of inflammation involves
      the sequential engagement of multiple cell adhesion molecules (CAMs) expressed on
      lymphocytes and endothelial cells. In addition, the expression of CAMs and the
      elaboration of matrix by subendothelial/submucosal cells may contribute to the
      retention and stimulation of infiltrating cells in an inflammatory lesion. We
      previously demonstrated that mitogen-activated T cells adhered to airway smooth
      muscle (ASM) in an integrin-dependent fashion. ASM are MHC class II-negative and
      expressed low basal levels of intercellular adhesion molecule-1 (ICAM-1). In this
      study, we demonstrate that anti-CD3-stimulated peripheral blood T cells also
      adhere to ASM and markedly upregulate ICAM-1 expression and induce the expression
      of MHC class II on ASM. The induction of HLA-DR was completely inhibited, and the
      induction of ICAM-1 partially inhibited, by neutralizing antibody against
      interferon-gamma. Furthermore, in studies with bronchoalveolar lavage-derived T
      cells isolated from atopic donors following local antigen challenge, we observed
      adhesion to ASM and upregulation of ASM expression of ICAM-1 and HLA-DR similar
      to that seen with in vitro-activated T cells. Finally, we found that despite
      expression of ICAM-1 and HLA-DR, ASM could not present alloantigen to CD4+ T
      cells. These findings suggest that the interaction of activated T cells with
      parenchymal cells of the lung such as airway smooth muscle affects the phenotype
      of myocytes and thus may have significant implications for inflammatory diseases
      such as asthma or transplant rejection.

PMID- 8998078
TI  - Decreased lung compliance and air trapping in heterozygous SP-B-deficient mice.
AB  - Genetic ablation of the murine SP-B gene in transgenic mice caused lethal
      perinatal respiratory distress in homozygous offspring, whereas heterozygous SP-B
      (+/-) mice survived postnatally. In adult SP-B(+/-) mice, surfactant protein B
      mRNA and the alveolar lavage SP-B protein were reduced by 50% compared with wild
      type littermates, consistent with the inactivation of a single SP-B allele.
      Expression of SP-A, SP-C, and SP-D proteins was not affected in SP-B(+/-) mice.
      Heterozygous SP-B(+/-) mice reached maturity in numbers expected by Mendelian
      inheritance of a recessive gene. Lung morphology and both intracellular and
      extracellular phospholipid pool size and composition were unaltered in the SP
      B(+/-) mice. Despite normal survival, pulmonary function studies demonstrated a
      consistent decrease in lung compliance in SP-B(+/-) mice. Abnormalities of
      inflation/deflation curves demonstrated airway collapse at low deflation
      pressures. Residual volumes were increased in the SP-B(+/-) mice. In summary, SP
      B mRNA and SP-B protein were reduced by 50% in SP-B(+/-) mice, resulting in
      abnormalities of lung compliance and air trapping, suggesting a potential
      susceptibility to pulmonary dysfunction associated with SP-B deficiency.

PMID- 8998079
TI  - Differentially regulated epithelial expression of an Eph family tyrosine kinase
      (fHek2) during tracheal surface airway and submucosal gland development.
AB  - A ferret model was used to evaluate the potential role of an Eph family tyrosine
      kinase (fHek2) in tracheal development of surface airway epithelium and
      submucosal glands. A partial 2.6-kb cDNA fragment of fHek2 was isolated from a
      ferret tracheal/lung cDNA library. Sequence analysis demonstrated that this gene
      is the ortholog to the previously cloned human Hek2 gene. In situ hybridization
      analysis of fHek2 mRNA expression on ferret tracheal developmental time points
      revealed an expression pattern within a subset of surface airway epithelial cells
      which remained relatively constant throughout tracheal development (from -2 d in
      utero to adult). In contrast, developing tracheal submucosal glands at 3-day
      postnatal time points demonstrated little fHek2 mRNA expression. However,
      expression of fHek2 significantly increased more than 4-fold over the course of
      gland development to adulthood. These findings, which demonstrate a uniquely
      regulated pattern of fHek2 mRNA expression between surface airway epithelium and
      submucosal glands, have implications on regulatory processes which control
      differentiation and/or maturation of secretory structures in the lung. Such
      findings may be useful in further delineating the mechanisms which control
      cellular differentiation in the lung and how these processes are abnormally
      regulated in hypersecretory diseases such as chronic bronchitis, asthma, and
      cystic fibrosis.

PMID- 8998080
TI  - Increased oxidative metabolism in cow tracheal epithelial cells cultured at air
      liquid interface.
AB  - Airway epithelial cells cultured at the air-liquid interface possess highly
      differentiated functions and structures compared with the cells cultured under
      immersion. We examined the oxidative metabolism and glycolysis in cow tracheal
      epithelial cells on Days 3, 6, 10, and 13, cultured under three different
      conditions: (1) immersion culture on porous filters with apical and basolateral
      feeding (IM), (2) air-exposed culture on porous filters with basolateral feeding,
      i.e., air-liquid interface culture (AI), and (3) conventional immersion culture
      in plastic dishes with apical feeding (DI). Lactate production was less in AI
      than in IM and DI on Day 3 through Day 13, whereas cellular adenosine
      triphosphate content and basal O2 consumption were greater. Ouabain-sensitive and
      ouabain-insensitive O2 consumption, and the uncoupled O2 consumption were also
      greater in AI. Cytosolic lactate dehydrogenase activities on Day 10 were lower in
      AI, whereas alpha-ketoglutarate dehydrogenase activities were higher. The
      increased oxidative metabolism in AI was more pronounced at the late phase of
      culture (Days 10 and 13). In contrast, glycolysis remained elevated during the
      experiment in IM and DI. These data suggest that (I) AI begins to promote
      oxidative metabolism from growth phase by the provision of adequate oxygenation,
      and then further shifts to oxidative metabolism with differentiation; and (2)
      apical feeding may be responsible for the disturbance of the development of the
      oxidative metabolism.

PMID- 8998081
TI  - Adoptively transferred late allergic airway responses are associated with Th2
      type cytokines in the rat.
AB  - Late allergic airway responses can be transferred by CD4+ T cells in the rat. To
      investigate the role of T-cell cytokines in these responses, we examined the
      expression of mRNA for Th2 (interleukin [IL]-4 and IL-5) and Th1 (IL-2 and
      interferon gamma [INF-gamma])-type cytokines in Brown Norway rats that were
      administered either antigen-primed W3/25(CD4)+ or OX8(CD8)+ T cells. Donors were
      actively sensitized by subcutaneous injection of ovalbumin (OVA) in the neck and
      T cells were obtained from the cervical lymph nodes by immunomagnetic cell
      sorting for administration to unsensitized rats. Control rats received bovine
      serum albumin (BSA)-primed CD4+ and CD8+ T cells. Two days later, recipient rats
      were challenged with aerosolized OVA, and bronchoalveolar lavage (BAL) was
      performed 8 h after challenge. BAL cells expressing mRNA for IL-2, IL-4, IL-5,
      and INF-gamma were analyzed using the technique of in situ hybridization.
      Recipients of OVA-primed CD4+ T cells had an increase in the fraction of BAL
      cells expressing mRNA for IL-4 and IL-5 compared with BSA-primed CD4+ or OVA
      primed CD8+ cells (P < 0.001). Recipients of CD8+ T cells had an increase in INF
      gamma mRNA expression after OVA challenge compared with recipients of BSA-primed
      CD8+ or OVA-primed CD4+ T cells (P < 0.001). In conclusion, T-cell-dependent
      allergen-induced late responses are associated with the expression of mRNA for IL
      4 and IL-5, indicating Th2 cell activation. Furthermore, the increased expression
      of INF-gamma in allergen challenge recipients of antigen-primed CD8+ T cells
      suggests that CD8+ T cells may be important in modulating allergic responses.

PMID- 8998082
TI  - Induction of emphysematous lesions in rat lung by beta-D-xyloside, an inhibitor
      of proteoglycan synthesis.
AB  - The possible involvement of proteoglycans in the pathogenesis of emphysema was
      studied in rats by a single intratracheal instillation of p-nitrophenyl-beta-D
      xylopyranoside (beta-D-xyloside), an inhibitor of proteoglycan synthesis. The
      first 3 days after instillation are characterized by mild hemorrhages, some
      infiltration of inflammatory cells, and edema. After 1 wk, lung morphology is
      normal again. Forty days after instillation, considerable parenchymal destruction
      has occurred as determined by the mean linear intercept (81 +/- 12 microns versus
      57 +/- 5 microns for control [P < 0.001]). Pulmonary fibrosis is not observed.
      Instillation with p-nitrophenyl-alpha-D-xylopyranoside and p-nitrophenol do not
      induce parenchymal destruction, indicating the specificity of beta-D-xyloside
      action. Urinary glycosaminoglycan (GAG) content of the beta-D-xyloside-treated
      rats is increased 15-fold during the first day after instillation, mainly due to
      elevated levels of chondroitin sulfate and dermatan sulfate. The increase is
      correlated to the extent of parenchymal destruction after 40 days (r = 0.68; P <
      0.002). At day 2 and thereafter, levels are normal again. A short-term increase
      in dermatan and chondroitin sulfate content is also observed in serum,
      bronchoalveolar lavage (BAL) fluid, and lung tissue. Heparan sulfate content is
      decreased in BAL fluid and lung tissue. Instillation with p-nitrophenyl-alpha-D
      xylopyranoside and p-nitrophenol do not induce elevated GAG concentration in
      urine. We suggest that a disturbance in proteoglycan synthesis accompanied by an
      increase of (beta-D-xyloside-primed) free GAGs results in loss of stability and
      integrity of the alveolar wall, leading to parenchymal destruction and
      emphysematous lesions. beta-D-xyloside treatment may be an alternative
      experimental method for inducing emphysema.

PMID- 8998083
TI  - TGF-beta 1 modulates human airway smooth-muscle cell proliferation induced by
      mitogens.
AB  - Asthma is a disease of airway inflammation and bronchoconstriction that results
      in airway smooth-muscle cell hypertrophy and hyperplasia. The underlying
      mechanisms that induce myocyte proliferation remain unknown. Evidence suggests
      that cytokines such as transforming growth factor (TGF)-beta 1 may play a role in
      modulating this process. In this study, we examined the effects of TGF-beta 1 on
      human airway smooth-muscle (HASM) cell proliferation. We found that treatment of
      HASM cells with TGF-beta 1 inhibited epidermal growth factor (EGF)- and thrombin
      induced DNA synthesis. This inhibition was both dose and time dependent. We then
      investigated whether these effects are mediated through activation of mitogen
      activated protein kinase (MAP kinase), an enzyme that is thought to play a
      central role in the regulation of cell proliferation. We found that MAP kinase
      activation induced by EGF was not modulated by TGF-beta 1, despite TGF-beta 1
      inhibiting EGF-induced HASM cell growth. These data suggest that TGF-beta 1
      inhibits mitogen-induced HASM cell proliferation, but does so downstream from MAP
      kinase activation, or via a parallel pathway that is independent of MAP kinase
      activation.

PMID- 8998084
TI  - Apoptosis and expression of Fas/Fas ligand mRNA in bleomycin-induced pulmonary
      fibrosis in mice.
AB  - The incidence of apoptosis and the expression of Fas antigen (Fas)/Fas ligand
      (FasL) mRNA in bleomycin-induced pulmonary fibrosis in mice were examined. Male
      ICR mice were intratracheally instilled with bleomycin (5 U/kg of body weight).
      The controls were injected with sterile saline. The animals were anesthetized and
      killed at 1, 6, and 12 h, and 1, 3, 5, 7, 9, and 14 days after bleomycin
      instillation. We assessed the incidence of apoptosis in lung tissues by DNA
      fragmentation on agarose gel electrophoresis, terminal deoxynucleotidyl
      transferase-mediated dUTP biotin nick end-labeling, and electron microscopy. The
      expression of Fas and FasL mRNA was detected by reverse transcription polymerase
      chain reaction (RT-PCR). The localization of Fas mRNA was analyzed by in situ
      hybridization and that of FasL mRNA was analyzed by RT in situ PCR. The results
      showed that (1) a single instillation of bleomycin leads to the rapid appearance
      of apoptosis in bronchial and alveolar epithelial cells, which resolves within 1
      day, and (2) apoptosis reappears on day 7 and continues for over 14 days after
      bleomycin instillation. This was accompanied with a progression of fibrosis.
      Corticosteroid administration completely blocked both apoptosis and fibrosis. The
      expression of Fas mRNA was upregulated in the alveolar epithelial cells by the
      bleomycin instillation. FasL mRNA was also upregulated in infiltrating
      lymphocytes after bleomycin treatment, but not in the control mice. The
      administration of corticosteroids suppressed the expression of Fas and FasL mRNA
      as well as apoptosis and fibrosis. Although these results do not show that
      apoptosis mediated by the Fas/FasL system is directly linked to bleomycin-induced
      fibrosis, we speculate that excessive apoptosis and the Fas/FasL system play a
      role in the pathogenesis of bleomycin-induced lung injury.

PMID- 8998085
TI  - An evaluation of technologies for identifying acute cardiac ischemia in the
      emergency department: executive summary of a National Heart Attack Alert Program
      Working Group Report.

PMID- 8998087
TI  - Cost-effectiveness of mandatory stress testing in chest pain center patients.
AB  - STUDY OBJECTIVE: To determine whether emergency patients with acute chest pain
      and low suspicion of acute myocardial infarction (AMI) can be managed cost
      effectively and safely in a dedicated chest pain center (CPC) that incorporates
      mandatory stress testing. METHODS: We assembled a prospective observational case
      series of consecutive adult patients transferred from the emergency department to
      a nine-bed, 23-hour CPC in a 564-bed community hospital from January 13 through
      May 31, 1994. In our institution, all emergency patients with acute nontraumatic
      chest pain of unclear origin, suggestive of myocardial ischemia but with a low
      probability of AMI, are transferred to the CPC for further evaluation. All
      patients in whom AMI is ruled out undergo individually appropriate cardiac
      diagnostic testing in accordance with CPC clinical guidelines. Patients with end
      stage coronary artery disease transferred to the CPC for a "rule-out" protocol
      only did not undergo further diagnostic testing. Admitted and discharged patients
      were followed through chart review and telephone survey, respectively. RESULTS:
      Of the 502 patients transferred to the CPC, 477 (95%) completed follow-up at 14
      days. Four hundred ten (86%) were discharged home. Those discharged after
      diagnostic evaluation yielded negative findings had 100% survival and zero
      diagnosis of AMI at 5-month follow-up. Overall mortality and incidence of AMI on
      long-term follow-up for all patients transferred to the CPC were .4% and .2%,
      respectively. Sixty-seven patients (13%) were admitted from the CPC, of whom 44
      (66%) had a final diagnosis of ischemic heart disease (IHD) or AMI. Twenty-four
      patients with IHD (55%; 6% of stress-tested group) were identified only on
      further stress testing. Of these patients, seven underwent percutaneous
      transluminal coronary angioplasty or coronary artery bypass grafting during
      hospitalization. All were discharged home without major morbidity. Four hundred
      twenty-four patients (84%) underwent stress testing. The cost of mandatory stress
      testing to identify one patient with IHD after AMI was ruled out was $3,125. An
      average cost-per-case savings of 62% was achieved for each patient transferred to
      the CPC who would have been hospitalized before the inception of the CPC.
      CONCLUSION: Mandatory stress testing is a safe, cost-effective, and valuable
      diagnostic and prognostic tool in CPC patients.

PMID- 8998086
TI  - An evaluation of technologies for identifying acute cardiac ischemia in the
      emergency department: a report from a National Heart Attack Alert Program Working
      Group.

PMID- 8998088
TI  - Feasibility of a rapid diagnostic protocol for an emergency department chest pain
      unit.
AB  - STUDY OBJECTIVE: To evaluate the applicability of a short-stay protocol for
      exclusion of acute ischemic heart disease without hospital admission and to
      analyze these results in the context of a conceptual model. METHODS: An
      observational study of patients who presented with chest pain to the emergency
      department of an 886-bed inner-city municipal hospital and who needed hospital
      admission to rule out acute myocardial infarction (AMI). Patients were assessed
      by ED attending physicians to determine eligibility for an alternative, 12-hour
      protocol in an ED chest pain observation unit (CPOU) followed by immediate
      exercise testing. Outcome measures were proportion of patients eligible for the
      short-stay protocol, risk factor profile, and reasons for exclusion. RESULTS: Of
      500 patients screened, 446 had sufficient data points to determine protocol
      eligibility. Of these, 238 (53.3%; 95% confidence interval [CI], 48.7% to 57.9%)
      were found to have low probability for AMI. After study exclusion criteria were
      applied to the patient cohort, 63 patients (14.1%; 95% CI, 10.9% to 17.3%) were
      eligible for the protocol. The most common reasons for exclusion were history of
      coronary artery disease (46%) and inability to perform an interpretable exercise
      tolerance test (42%). CONCLUSION: Although most admitted patients with chest pain
      (53%) were at low probability for AMI, only a minority (14%) were eligible for a
      short-stay protocol that required patients to be free of known coronary artery
      disease and able to perform an exercise tolerance test. Factors affecting the
      operations and efficiency of a CPOU include clinical characteristics of the
      target patient population, protocol tests used, and hospital occupancy and
      reimbursement patterns.

PMID- 8998089
TI  - Patient satisfaction with an emergency department chest pain observation unit.
AB  - STUDY OBJECTIVE: Patient satisfaction is an essential outcome measure in the
      diagnosis and treatment of acute chest pain in the emergency department. We
      compared patient satisfaction with the diagnostic protocol of a chest pain
      observation unit (CPOU) and standard inpatient hospitalization. METHODS: We
      prospectively studied patients who presented to the ED with chest pain and were
      found to have a low risk of acute myocardial infarction (AMI) but who still might
      have benefited from a diagnostic protocol to rule out AMI. Consenting patients (N
      = 104) were randomized to the CPOU (experimental) arm or the hospital inpatient
      (control) arm and assessed for satisfaction by means of an interview before
      hospital discharge. RESULTS: The CPOU protocol scored higher on four summary
      ratings of overall patient satisfaction. Correlations between overall
      satisfaction, number, and type of problems with care, and patient characteristics
      demonstrated content validity and revealed strengths and improvements that might
      be made in CPOUs. CONCLUSION: Patients were more satisfied with rapid diagnosis
      in the CPOU than with inpatient stays for acute chest pain. Our findings add
      important information to the standard practice of weighing clinical and cost
      outcomes between two medical care alternatives.

PMID- 8998090
TI  - Comprehensive strategy for the evaluation and triage of the chest pain patient.
AB  - STUDY OBJECTIVE: To evaluate the safety and efficacy of a systematic evaluation
      and triage strategy including immediate resting myocardial perfusion imaging in
      patients presenting to the emergency department with chest pain of possible
      ischemic origin. METHODS: We conducted an observational study of 1,187
      consecutive patients seen in the ED of an urban tertiary care hospital with the
      chief complaint of chest pain. Within 60 minutes of presentation, each patient
      was assigned to one of five levels on the basis of his or her risk of myocardial
      infarction (MI) or unstable angina (UA): level 1, MI; level 2, MI/UA; level 3,
      probable UA; level 4, possible UA; and level 5, noncardiac chest pain. In the
      lower risk levels (3 and 4), immediate resting myocardial perfusion imaging was
      used as a risk-stratification tool alone (level 4) or in combination with serial
      markers (level 3). RESULTS: Acute MI, early revascularization indicative of acute
      coronary syndrome, or both were consistent with risk designations: level 1: 96%
      MI, 56% revascularization; level 2: 13% MI, 29% revascularization; level 3: 3%
      MI, 17% revascularization; level 4: .7% MI; 2.5% revascularization. Sensitivity
      of immediate resting myocardial perfusion imaging for MI was 100% (95% confidence
      interval [CI], 64% to 100%) and specificity 78% (74% to 82%). In patients with
      abnormal imaging findings, risk for MI (7% versus 0%, P < .001; relative risk
      [RR], 50; 95% CI, 2.8 to 889) and for MI or revascularization (32% vs 2%, P <
      .001; RR, 15.5; 95% CI, 6.4 to 36) were significantly higher than in patients
      with normal imaging findings. During 1-year follow-up, patients with normal
      imaging findings (n = 338) had an event rate of 3% (revascularization) with no MI
      or death (combined events: negative predictive value, 97%; 95% CI, 95% to 98%).
      Patients with abnormal imaging findings (n = 100) had a 42% event rate (combined
      events: RR, 14.2; 95% CI, 6.5 to 30; P < .001), with 11% experiencing MI and 8%
      cardiac death. CONCLUSION: This strategy is a safe, effective method for rapid
      triage of chest pain patients. Rapid perfusion imaging plays a key role in the
      risk stratification of low-risk patients, allowing discrimination of unsuspected
      high risk patients who require prompt admission and possible intervention from
      those who are truly at low risk.

PMID- 8998091
TI  - Effectiveness of verapamil-quinidine versus digoxin-quinidine in the emergency
      department treatment of paroxysmal atrial fibrillation.
AB  - STUDY OBJECTIVE: To determine the relative effectiveness of a verapamil-quinidine
      sequential combination versus digoxin-quinidine in the emergency department
      treatment of paroxysmal atrial fibrillation (PAF). METHOD: This prospective,
      double-blind, randomized, controlled trial involved patients, aged 18 to 75
      years, with new-onset (< 48 hours) atrial fibrillation who presented to a
      community-based urban hospital with an annual ED census of 65,000. Exclusion
      criteria included ventricular response rate lower than 100 or higher than 200
      beats/minute, allergy to study drugs, hypotension with evidence of end-organ
      hypoperfusion, and conduction abnormalities. Consenting patients were randomly
      assigned to receive rapid digitalization (1.0 mg over 2 hours) or i.v. verapamil
      (sequential 5-mg boluses up to 20 mg). After ventricular rate was controlled (<
      100 beats/minute), oral quinidine (200 mg) was initiated and repeated every 2
      hours until conversion to normal sinus rhythm (NSR) occurred, until 1 g of
      quinidine was administered, or until adverse effects supervened. Heart rate,
      blood pressure, cardiac rhythm, time to conversion, and adverse effects were
      documented. RESULTS: Forty-four patients received the study drugs. Three were
      withdrawn, leaving 19 in the verapamil-quinidine (VER-Q) group and 22 in the
      digoxin-quinidine (DIG-Q) group. Sixteen patients (84%) in the VER-Q group and 10
      (45%) in the DIG-Q group converted to NSR within 6 hours (P < .02). Mean time to
      conversion (+/-SD) was 185 +/- 146 minutes for VER-Q and 368 +/- 386 minutes for
      DIG-Q patients (P = NS). Twelve VER-Q patients (63%) and 6 DIG-Q patients (27%)
      were discharged from the ED (P < .05). Minor adverse effects were more common in
      the VER-Q group. No mortality or significant morbidity occurred. CONCLUSION: The
      sequential combination of verapamil and quinidine, in the doses studied, is an
      effective treatment for PAF and is superior to digoxin-quinidine. Digoxin should
      no longer be considered the treatment of choice for uncomplicated PAF.

PMID- 8998092
TI  - Emergency management of atrial fibrillation and flutter: intravenous diltiazem
      versus intravenous digoxin.
AB  - STUDY OBJECTIVE: To compare the effects of i.v. diltiazem and i.v. digoxin on
      ventricular rate control in the emergency treatment of acute atrial fibrillation
      and flutter (AFF). METHODS: This prospective, randomized, open-label trial
      involved 30 consecutive patients who presented with acute AFF to the emergency
      department of an urban, 420-bed community teaching hospital from April 1993
      through March 1994. Exclusion criteria included systolic blood pressure lower
      than 100 mm Hg, treatment with calcium-channel blockers other than diltiazem,
      lack of informed consent, and objection of the private physician. Patients were
      randomly assigned to receive either i.v. diltiazem alone, i.v. digoxin alone, or
      both. Heart rate control was defined as a ventricular rate of less than 100
      beats/minute. I.v. digoxin, 25 mg, was given as a bolus at time 0 and at time 30
      minutes. An initial dose of .25 mg/kg diltiazem was given intravenously over the
      first 2 minutes, followed by a dose of .35 mg/kg at time 15 minutes and then a
      titratable i.v. infusion at a rate of 10 to 20 mg/hour to maintain heart rate
      control. The dosing regimens were the same whether the drugs were given alone or
      in combination. Heart rhythm, heart rate, and blood pressure were measured at
      time 0, 5, 10, 15, 30, 60, 120, and 180 minutes. Statistical significance was
      assessed with the use of Student's t test and ANOVA methodology. RESULTS: At time
      0, the heart rate (mean +/- SD) was 150 +/- 19 beats/minute in the diltiazem
      group and 144 +/- 12 in the digoxin group (difference not significant, P = .432).
      The decrease in heart rate from time 0 reached statistical significance at time 5
      minutes in the diltiazem group (P = .0006); the mean rates at time 5 minutes were
      111 +/- 26 beats/minute for diltiazem and 144 +/- 13 for digoxin. The decrease in
      heart rate achieved with digoxin did not reach statistical significance until
      time 180 minutes (P = .0099), at which time the rates were 90 +/- 13 for
      diltiazem and 117 +/- 22 for digoxin. CONCLUSION: Treatment of acute AFF with
      i.v. diltiazem decreases ventricular heart rate significantly within 5 minutes,
      compared with 3 hours for treatment with i.v. digoxin. No advantage was noted
      within 3 hours for i.v. treatment with a combination of diltiazem and digoxin.
      I.v. diltiazem is superior to i.v. digoxin in the emergency control of
      ventricular rate in acute AFF and should be considered as a drug of choice for
      this condition. This study was not large enough to adequately assess adverse
      effects, and further studies may be warranted for clinical validation.

PMID- 8998093
TI  - Depression screening in adolescents with somatic complaints presenting to the
      emergency department.
AB  - STUDY OBJECTIVE: To determine the frequency of documented depression screening
      for adolescents presenting with somatic chief complaints to a pediatric emergency
      department. METHODS: We conducted a retrospective chart review of 408 consecutive
      patients aged 11 to 17 years who presented to the ED with a chief complaint of
      chest pain, abdominal pain, headache, weakness/fatigue, dizziness/fainting, or
      hyperventilation. RESULTS: Documentation of depression screening was noted in
      4.2% of cases (17 of 408). For patients charts listing both a somatic chief
      complaint and a similar nonspecific discharge diagnosis, the documentation rate
      for depression screening rose to 7.5%. No change in screening documentation was
      noted for chronically ill patients. We did detect a significant difference in
      screening frequency between black adolescents and adolescents of all other races
      (P = .021). CONCLUSION: Our findings demonstrate an extremely low frequency of
      documentation of depression screening in adolescents with somatic complaints
      presenting to the ED. Documentation of screening in black patients was still low
      but was performed at a significantly higher rate. These results indicate a need
      for education on the adolescent at risk for depression and suicide in the acute
      care setting.

PMID- 8998094
TI  - Intravenous ketamine sedation of pediatric patients in the emergency department.
AB  - STUDY OBJECTIVE: To determine efficacy, safety, recovery times, and parental
      satisfaction with i.v. ketamine sedation in pediatric patients requiring brief,
      painful procedures in the emergency department. METHODS: Pediatric ED patients
      whom we found to require brief (< 10 minutes), painful procedures were considered
      candidates for ketamine sedation. Each subject received 1.0 to 2.0 mg/kg i.v.
      ketamine, after which the necessary procedure was performed. RESULT: Thirty
      patients, ranging in age from 18 months to 8 years, were enrolled in the study.
      With the exception of one patients in whom ketamine was inadvertently given
      subcutaneously, all subjects given i.v. ketamine exhibited sedation adequate for
      the planned painful procedure within 2 minutes of ketamine administration. An
      initial bolus of 1.0 mg/kg required supplemental administration of ketamine in
      50% of the patients (6 of 12), whereas an initial bolus of 1.5 mg/kg reliably
      produced adequate sedation in 94% (17 of 18). The median time elapsed before the
      criteria for discharge after injection were fulfilled was 25 minutes. No
      deleterious cardiopulmonary effects were noted. Vomiting and mild agitation after
      the procedure were observed in two and four cases, respectively. At follow-up all
      parents reported satisfaction with ketamine sedation. CONCLUSION: I.v. ketamine
      is a consistently effective method of producing a rapid, brief period of profound
      sedation and analgesia in children in the ED. Although no serious complications
      were noted in our series, larger studies are needed to establish this drug's
      safety profile in the ED. Vomiting, ataxia, and agitation were noted in a few
      cases.

PMID- 8998095
TI  - Symptomatology of HIV-related illness and community-acquired illness in an HIV
      infected emergency department population.
AB  - STUDY HYPOTHESIS: Community-acquired infections and non-AIDS-related illnesses
      are a significant proportion of the final diagnoses in HIV-infected patients
      presenting to an emergency department. We hypothesized that emergency physicians
      over-diagnose opportunistic infections in the HIV-infected patient. We also
      hypothesized that the absolute CD4 lymphocyte level could be used to stratify
      patients by likelihood of HIV related disease. METHODS: We retrospectively
      reviewed ED logbooks and medical records to find all ED patients with self
      reported HIV seropositivity during a 19-month period. Age, sex, insurance status,
      chief complaint(s), ED assessment, and disposition were recorded from the ED
      logs; absolute CD4 lymphocyte counts, risk factors, and final diagnoses were
      recorded from the medical records. HIV-related disease was evaluated with the use
      of established Centers for Disease Control and Prevention criteria. Data were
      evaluated with the use of the chi 2 test, the chi 2 test for trend, and kappa
      proportions. RESULTS: Analysis of 344 ED visits demonstrated that decreasing
      absolute CD4 lymphocyte counts were associated with increasing incidence of HIV
      related disease (P < .001), even when noninfectious causes were excluded. Only
      34% of visits were related to HIV-associated illness. Emergency physicians
      exhibited high sensitivity (72.9%) and specificity (95.5%) in diagnosing HIV
      related disease and conducted appropriate visit disposition. CONCLUSION: ED
      visits by HIV-infected individuals are often not made for reasons of
      opportunistic infection, and the absolute CD4 lymphocyte count is inversely
      related to HIV-related disease.

PMID- 8998097
TI  - Chest pain evaluation: through a glass darkly.

PMID- 8998098
TI  - Randomized trials and common sense.

PMID- 8998096
TI  - Visual acuity after topical application of proparacaine.
AB  - STUDY OBJECTIVE: To determine the effect of topical anesthetics on visual acuity
      (VA). METHODS: We studied 66 consecutive patients (73 afflicted eyes) who
      presented to a university hospital emergency department with the complaint of eye
      pain. VA was measured before and after patients were treated with proparacaine, a
      topical ocular anesthetic. RESULTS: After proparacaine instillation, VA was
      improved in 33 patients (45%), unchanged in 34 (47%), and worse in 6 (8%).
      CONCLUSION: Patients with eye pain often demonstrate improved VA after the
      instillation of a topical anesthetic.

PMID- 8998099
TI  - Refining the classification of chest pain: a logical next step in the evaluation
      of patients for acute cardiac ischemia in the emergency department.

PMID- 8998100
TI  - Chest pain units: do they make sense now?

PMID- 8998101
TI  - Adenosine in wide-complex tachycardia.
AB  - The use of adenosine as a therapeutic and diagnostic tool in wide-complex
      tachycardia is suggested in the current Advanced Cardiac Life Support (ACLS)
      guidelines. The ACLS guidelines are now 4 years old, and new information on the
      safety and efficiency of adenosine in wide-complex tachycardia is available. We
      review the ACLS recommendations in light of the current available literature. In
      general, the ACLS recommendations remain reasonable with some important caveats.

PMID- 8998102
TI  - Fatal myocardial infarction resulting from coronary artery septic embolism after
      abortion: unusual cause and complication of endocarditis.
AB  - Significant medical complications after elective abortion are rare. However,
      complications do occur, and the emergency physician should always bear this in
      mind when evaluating a patient with significant illness who has recently
      undergone an elective abortion. Reported here is a case of postabortion
      endocarditis, manifesting as a septic coronary artery embolism, that led to a
      fatal acute myocardial infarction.

PMID- 8998103
TI  - Myocardial infarction resulting from caffeine overdose in an anorectic woman.
AB  - A 20-year-old bulimic woman ingested 20 g of caffeine in a suicide attempt. After
      being evaluated and discharged from the emergency department, she was readmitted
      with ECG changes and ultimately found to have sustained a subendocardial
      infarction. This case highlights the wide-ranging health consequences of eating
      disorders and the toxicity of caffeine overdose.

PMID- 8998104
TI  - Glucagon therapy in the treatment of symptomatic bradycardia.
AB  - Symptomatic bradycardia is commonly seen in the emergency department. Effective
      drug therapy for this clinical scenario is limited. Although glucagon has been
      used in no clinical trial in this setting, its cardiac activity may prove useful,
      particularly in the setting of beta-adrenergic blockade. We report a case series
      comprising three patients taking maintenance beta-blocker therapy who presented
      to the ED with symptomatic bradycardia and hypotension and in whom glucagon
      therapy obviated the need for further treatment. Further study is warranted to
      evaluate and define the role of glucagon in the treatment of symptomatic
      bradycardia.

PMID- 8998105
TI  - Eventually all of us must die.

PMID- 8998107
TI  - COBRA: tempest in a teapot?

PMID- 8998106
TI  - Radiograph review revisited.

PMID- 8998109
TI  - COBRA: tempest in a teapot?

PMID- 8998108
TI  - COBRA: tempest in a teapot?

PMID- 8998110
TI  - Rapid-sequence intubation revisited.

PMID- 8998111
TI  - Tetanus immunization.

PMID- 8998112
TI  - Potential danger of nalmefene use in the emergency department.

PMID- 8998113
TI  - Severe hyponatremia after "purification".

PMID- 8998114
TI  - Exotic envenomation.

PMID- 8998116
TI  - Advances in the care of the patient with malignant melanoma.

PMID- 8998115
TI  - Recent advances in the care of the patient with malignant melanoma.
AB  - OBJECTIVE: The authors review the recent advances in the surgical care, staging,
      and adjuvant treatment of the patient with melanoma. SUMMARY BACKGROUND DATA:
      Melanoma care has not changed significantly in the last 20 years, and the
      controversy of elective lymph node dissections in this disease continues to be
      discussed. Two advances in the care of the patient with melanoma have occurred in
      the last 3 years to make this an exciting time for clinicians and to offer more
      hope for the patients with this disease. The concept of the sentinel lymph node
      (SLN), defined by Morton as the first node in the lymphatic basin that drains the
      primary melanoma, has been documented to contain the first site of metastatic
      disease. This technology can be used to stage nodally the melanoma patient,
      identifying the subgroup of patients (stage III) who have a 5-year survival rate
      less than 50%. Members of this group are candidates for effective adjuvant
      therapies. METHODS: A review of the surgical techniques of melanoma care,
      including recently reported new studies of elective node dissection (ELND) and
      SLN biopsy in patients with melanoma was performed. In addition, the Eastern
      Cooperative Oncology Group (ECOG) 1684 trial, which was the basis for the Food
      and Drug Administration approval of adjuvant interferon-alpha-2b (IFN-alpha-2b)
      is discussed. RESULTS: The Intergroup Melanoma Trial has reported a survival
      benefit for performing ELND in patients with melanoma and tumor thickness between
      1 and 2 mm or in patients that are younger than 60 years of age. With six reports
      in the literature that show there is an order to melanoma nodal metastases and
      that the SLN histology is reflective of the histology of the remainder of the
      nodal basin, the more conservative SLN biopsy can be performed to adequately
      stage nodally the patient with melanoma. Patients with nodal metastases who are
      rendered free of disease with surgical resection have the most to benefit from
      adjuvant IF-alpha-2b. If one considers only the lymph node-positive group of
      patients, the survival benefit associate with adjuvant IFN is significant (p =
      0.008). CONCLUSIONS: New standards of care for the melanoma patient have been
      established. Patients at high risk for recurrence have been shown to experience a
      survival benefit with adjuvant IFN-alpha-2b. With these data, the argument can be
      made that all patients with melanoma greater than 1 mm should have a nodal
      staging procedure. Selective lymphadenectomy with SLN biopsy is the least morbid
      procedure that can be used to obtain this information. If surgeons do not have
      the nuclear medicine or pathology support to perform lymphatic mapping, then the
      guidelines of the Intergroup Melanoma Study should be used to apply ELND in a
      selective fashion. In this way, patients are identified with micrometastatic
      disease early in their clinical course and can be offered the survival benefit of
      adjuvant therapy.

PMID- 8998118
TI  - Laparoscopic repair of paraesophageal hernia.
AB  - OBJECTIVE: The purpose of this report is to describe the authors' technique for
      the laparoscopic repair of paraesophageal hernias and the outcome in their series
      of patients. METHODS: Thirty patients underwent elective laparoscopic repair of
      paraesophageal hernias. All were pure type II paraesophageal hernias as defined
      by upper gastrointestinal contrast studies. All operations were performed by a
      single surgeon (JKE) assisted by five different chief surgical residents. The
      authors have used various prototypes of a laparoscopic utility belt to reduce the
      physician requirement to the surgeon and a first assistant. The operative setup
      and specific techniques of the repair are described and illustrated. A
      concomitant anti-reflux procedure was performed in the last 23 patients. RESULTS:
      Satisfactory repair using video-laparoscopic techniques was achieved in all
      cases. There were no deaths. Complications occurred in 8 of 30 patients.
      Postoperative gastroesophageal reflux developed in three of the first seven
      patients in whom fundoplication was not performed. Three consecutive patients had
      left lower lobe atelectasis believed to be related to endotracheal tube
      displacement during the passage of the bougie. One patient had postoperative
      dysphagia. There was one case of major deep venous thrombosis with pulmonary
      embolism. Twenty-eight of 30 patients were discharged home by postoperative day
      3. Twenty-four of 30 patients had returned to normal activity by the time of
      their first postoperative office visit 1 week after surgery.

PMID- 8998117
TI  - Barrett's esophagus. The significance of p53 in clinical practice.
AB  - OBJECTIVE: The authors provide an updated review the molecular biology of the p53
      tumor suppressor gene with reference to its role in the malignant degeneration of
      Barrett's esophagus. SUMMARY BACKGROUND DATA: Appreciation of the function of the
      tumor suppressor gene p53 has given new insight into regulation of the cell
      cycle, and the gene appears to play an important role in many solid tumors.
      Esophageal adenocarcinoma is increasing in frequency in the western world at an
      alarming rate and is unique because there is a clear metaplasia (Barrett's
      mucosa)/ dysplasia/carcinoma sequence. p53 malfunction arises as an early event
      in this carcinogenic process and has been demonstrated in patients with
      nondysplastic Barrett's metaplasia. The possible causes of p53 malfunction in
      this setting are discussed. The most reliable method for the detection of p53
      mutations is DNA sequencing. p53 immunohistochemistry appears too insensitive to
      act as a reliable marker for the presence of a mutation and cannot be used as a
      reliable marker for the future development of cancer. CONCLUSIONS: High-grade
      dysplasia within Barrett's mucosa remains the best clinical predictor of
      adenocarcinoma. The mutational spectrum observed in these tumors should provide
      clues to their etiology.

PMID- 8998119
TI  - Place of cryosurgery in the treatment of malignant liver tumors.
AB  - OBJECTIVE: The authors evaluate the results of cryosurgery in malignant liver
      tumors. SUMMARY BACKGROUND DATA: The outcome of primary or secondary liver tumors
      is poor when resection can not be achieved. Encouraging results of cryosurgery
      have been reported in unresectable liver tumors, but this treatment needs further
      evaluation of its efficacy in homogeneous groups of patients. METHODS: From 63
      patients with malignant liver tumors with various histology treated by
      cryosurgery in a 2.5-year period, the authors evaluated the results of 34
      patients with nonresectable hepatocellular carcinoma (9 patients) or
      nonresectable metastases from colorectal cancer (25 patients). Cryosurgery was
      used either as a single treatment (4 hepatocellular carcinomas, 5 metastases) or
      in association with liver resection (5 hepatocellular carcinomas, 20 metastases).
      Systemic chemotherapy was used routinely before surgery and after surgery.
      RESULTS: There was no intraoperative mortality. Mortality within 2 months was 3%
      and was unrelated to the procedure. Postoperative morbidity consisted of one
      sterile fluid collection and one biliary fistula (8%). At a mean follow-up of 16
      months, (range, 2-27) local recurrence rate was 0% for hepatocellular carcinoma
      and 44% for metastases. Cumulative survival at 24 months was 63% and 52%,
      respectively, with 6 patients (67%) and 5 patients (20%) currently disease free.
      In the group of patients with metastases, survival was related to the size of the
      treated tumor (p = 0.06) and the absence of residual disease (p = 0.03).
      CONCLUSIONS: Cryosurgery is safe and increases the number of patients with
      unresectable liver malignancies in whom surgery can aim at eradicating the tumor.
      Local recurrence is observed more frequently for metastases than for
      hepatocellular carcinoma. The benefit in survival is related to the complete
      treatment of the tumoral disease.

PMID- 8998120
TI  - Repeat hepatectomy for colorectal liver metastases.
AB  - OBJECTIVE: The authors assess the long-term results of repeat hepatectomies for
      recurrent metastases of colorectal cancer and determine the factors that can
      predict survival. SUMMARY BACKGROUND DATA: Safer techniques of hepatic resection
      have allowed surgeons to consider repeat hepatectomy for colorectal metastases in
      an increasing number of patients. However, higher operative bleeding and
      increased morbidity have been reported after repeat hepatectomies, and the long
      term benefit of these procedures needs to be evaluated. STUDY POPULATION: Sixty
      four patients from a group of 243 patients resected for colorectal liver
      metastases were submitted to 83 repeat hepatectomies (64 second, 15 third, and 4
      fourth hepatectomies). Combined extrahepatic surgery was performed in 21 (25%) of
      these 83 repeat hepatectomies. RESULTS: There was no intraoperative or
      postoperative mortality. Operative bleeding was not significantly increased in
      repeat hepatectomies as compared to first resections. Morbidity and duration of
      hospital stay were comparable to first hepatectomies. Overall and disease-free
      survival after a second hepatectomy were 60% and 42%, respectively, at 3 years
      and 41% and 26%, respectively, at 5 years. Factors of prognostic value on
      univariate analysis included the curative nature of first and second
      hepatectomies (p = 0.04 and p = 0.002, respectively), an interval between the two
      procedures of more than 1 year (p = 0.003), the number of recurrent tumors (p =
      0.002), serum carcinoembryonic antigen levels (p = 0.03), and the presence of
      extrahepatic disease (p = 0.03). Only the curative nature of the second
      hepatectomy and an interval of more than 1 year between the two procedures were
      independently related to survival on multivariate analysis. CONCLUSIONS: Repeat
      hepatectomies can provide long-term survival rates similar to those of first
      hepatectomies, with no mortality and comparable morbidity. Combined extrahepatic
      surgery can be required to achieve tumor eradication. Repeat hepatectomies appear
      worthwhile when potentially curative.

PMID- 8998121
TI  - Bilateral adrenalectomy for Cushing's syndrome. Anterior versus posterior
      surgical approach.
AB  - OBJECTIVE: This study evaluates the intraoperative and postoperative
      complications in patients with Cushing's syndrome who underwent bilateral
      adrenalectomy comparing the posterior or anterior operative approach. BACKGROUND:
      The posterior approach for bilateral adrenalectomy has been advocated over the
      anterior approach because of rapid recovery and decreased morbidity, but the long
      term complications associated with each procedure are not well described.
      METHODS: The intraoperative profiles and morbidity in 48 patients undergoing
      bilateral adrenalectomy for Cushing's disease through either the anterior or
      posterior approach from 1985 to the present were reviewed comparing the
      intraoperative complication and early and late postoperative complication rate
      and morbidity. RESULTS: Twenty-seven patients underwent an anterior
      transabdominal procedure, whereas 21 underwent a posterior retroperitoneal
      procedure via bilateral incisions. Age, weight, and diagnostic categories of
      Cushing's syndrome were similar between the two groups as well as serum cortisol
      and 24-hour urinary cortisol levels. Operative time, estimated blood loss, and
      transfusion requirements were not different between the groups, even though
      adrenal glands excised through the anterior approach were significantly larger.
      Acute morbidity was similar between the groups. However, 17 (81%) of 21 patients
      who underwent posterior bilateral adrenalectomy suffered from chronic back pain,
      compared with 2 (7%) of 27 via the anterior approach. Five of these patients in
      the posterior group considered the pain incapacitating, and the mean time to
      return to work was significantly longer in the posterior group because of back
      pain. CONCLUSIONS: The anterior approach to bilateral adrenalectomy has
      comparable intraoperative complications and early morbidity compared to the
      posterior approach. The posterior approach has a very high incidence of chronic
      incision-related back pain. The anterior approach is the preferred open surgical
      technique in most patients undergoing bilateral adrenalectomy for Cushing's
      syndrome without other contraindications for undergoing laparotomy.

PMID- 8998122
TI  - Risk of contralateral breast cancer among women with carcinoma in situ of the
      breast.
AB  - BACKGROUND: Information is limited on the risk of contralateral breast cancer
      after a diagnosis of breast carcinoma in situ (BCIS). METHODS: In western
      Washington, between 1974 and 1993, 1929 women with a first primary ductal
      carcinoma in situ (DCIS) and 282 women with a first primary lobular carcinoma in
      situ (LCIS) were followed for contralateral breast cancer. Rates of contralateral
      invasive breast cancer and BCIS were compared with population rates of first
      primary breast cancer using Poisson regression to adjust for age and calendar
      year. RESULTS: The rate of contralateral invasive disease after BCIS was
      approximately twice the population rate for women with DCIS and three times the
      population rate for women with LCIS; relative rates decreased somewhat with
      increasing time since diagnosis of LCIS, but were fairly stable after DCIS. The
      relative rate of contralateral DCIS after BCIS was substantially higher than for
      contralateral invasive disease, but dropped dramatically after the first year
      after the initial BCIS, especially among women with LCIS. Contralateral BCIS
      usually was of the same histologic type as the initial BCIS; histologic
      concordance of BCIS was 71% for women with an initial LCIS and 78% for women with
      DCIS. CONCLUSIONS: Data suggest that the rate of contralateral invasive breast
      cancer is elevated for at least 5 years after a diagnosis of BCIS compared with
      the rate of first primary breast cancer in the population, and that the rate is
      only slightly higher for women with LCIS than for women with DCIS. The markedly
      elevated rate of contralateral DCIS may result in large part from increased
      medical surveillance of women diagnosed with BCIS, especially during the first
      year after the initial diagnosis.

PMID- 8998124
TI  - Low-dose recombinant human growth hormone increases body weight and lean body
      mass in patients with short bowel syndrome.
AB  - OBJECTIVE: The authors investigate the effects of low dose recombinant human
      growth hormone (rhGH) on body composition and absorptive capacity in patients
      with short bowel syndrome from Crohn's disease. SUMMARY BACKGROUND DATA: Patients
      with short bowel syndrome usually are malnourished because of malabsorption. The
      anabolic effects of high doses of rhGH have been tested in different clinical
      catabolic conditions, recently including patients with short bowel syndrome. The
      authors have investigated the effects of low-dose rhGH in short bowel syndrome in
      a placebo-controlled crossover clinical trial. METHODS: Ten patients were treated
      with daily subcutaneous doses of rhGH/placebo (0.5 international units/kg-1 per
      week-1 = 0.024 mg/kg-1 per day-1) for 8 weeks in a randomized, double-blind,
      placebo-controlled crossover clinical trial with a minimum of 12 weeks wash-out.
      Absorptive capacity and biochemical parameters were investigated in a metabolic
      ward before treatment and during first and last week of treatment. Body
      composition was determined by DEXA-Scan (Lunar DPX, Scanexport Medical,
      Helsingborg, Sweden), impedance analysis, and whole body potassium counting.
      RESULTS: Low-dose rhGH doubled serum levels of insulin-like growth factor-1 (IGF
      1) and increased body weight, lean body mass, and total body potassium by 5% (p <
      0.05). Fat-free mass and total body water increased by 6% (p = 0.008). Increases
      in IGF-1 levels correlated with increases in fat-free mass (r = 0.77, p < 0.02).
      No significant changes in absorptive capacity of water, energy, or protein were
      detected. CONCLUSION: Eight weeks of low-dose rhGH treatment leads to increases
      in body weight, lean body mass, and fat-free mass in patients with short bowel
      syndrome, correlated to increases in IGF-1 levels.

PMID- 8998125
TI  - Both growth hormone and exogenous glutamine increase gastrointestinal glutamine
      uptake in trauma.
AB  - OBJECTIVE: The authors studied the effect of exogenous glutamine (GLN), with and
      without growth hormone (GH), pretreatment, on gastrointestinal, hepatic, femoral,
      and renal GLN fluxes. SUMMARY BACKGROUND DATA: Growth hormone treatment increases
      gastrointestinal uptake of GLN despite a reduced skeletal muscle and whole body
      release. METHODS: Piglets were randomized to a GH + GLN group (n = 8), a GLN
      group (n = 8), a GH group (n = 8), and a control group (CON; n = 8). Genotropin
      (Pharmacia, Stockholm, Sweden; 24 international units; correspondingly saline in
      the GLN and the CON group) was given daily 3 days before and at the onset of
      trauma (surgery). Organ fluxes and whole body release of GLN were determined 1
      and 5 hours after surgery. An infusion of GLN 36 micrograms/kg per minute was
      started after the first measurement in the GH + GLN and the GLN groups. RESULTS:
      Both GH treatment and exogenous GLN increased gastrointestinal GLN uptake (p =
      0.001 and p = 0.02, respectively). Growth hormone treatment reduced hepatic GLN
      uptake (p = 0.001). Hepatic GLN uptake was lower in the GH + GLN group versus the
      GH group (p = 0.02), but not in the GLN group versus the CON group (p = 0.98).
      Growth hormone treatment reduced femoral and whole-body GLN release (p = 0.0001
      and p = 0.02, respectively). Renal GLN uptake was higher in the two GH-treated
      groups (p = 0.003). CONCLUSION: Both exogenous GLN and GH increased
      gastrointestinal GLN uptake, and the combination was additive. In contrast to
      exogenous GLN, GH reduced hepatic uptake and consequently facilitated the
      increased gastrointestinal GLN uptake that occurred despite reduced femoral and
      whole-body release.

PMID- 8998126
TI  - Modulation of human hepatocyte acute phase protein production in vitro by n-3 and
      n-6 polyunsaturated fatty acids.
AB  - OBJECTIVE: The authors investigate the role of a variety of essential
      polyunsaturated fatty acids on the spontaneous and interleukin-6 stimulated
      production of acute phase proteins by isolated human hepatocytes. SUMMARY
      BACKGROUND DATA: The altered production of acute phase proteins by the liver is
      one of the principal effects of the systemic inflammatory response in human
      disease. It has been shown that polyunsaturated fatty acids have certain anti
      inflammatory properties that potentially are mediated through altered
      prostaglandin or proinflammatory cytokine production. However, the effect of
      polyunsaturated fatty acids on the responsiveness of the human hepatocyte to
      proinflammatory cytokines has not been studied in detail. METHODS: Hepatocytes
      isolated from human livers were maintained in primary culture in the presence of
      a variety of bovine serum albumin-complexed fatty acids. The influence of these
      fatty acids on hepatocyte acute phase protein production was assessed, in the
      presence and absence of recombinant interleukin-6, by measurement of acute phase
      proteins by enzyme-linked immunosorbent assay. RESULTS: Eicosapentaenoic and
      gammalinolenic acid increased spontaneous production of alpha 1-antichymotrypsin
      and prealbumin but decreased spontaneous production of transferrin and
      haptoglobin from isolated human hepatocytes. Eicosapentaenoic and gammalinolenic
      significantly increased interleukin-6-stimulated production of C-reactive protein
      and alpha 1-antichymotrypsin but reversed the stimulatory effect of interleukin-6
      on haptoglobin production. These fatty acids also reversed the inhibitory effect
      of interleukin-6 on prealbumin production. CONCLUSIONS: These results show that
      certain fatty acids have the potential to modulate spontaneous and cytokine
      induced alterations in human hepatic acute phase protein metabolism. These data
      indicate the presence of complex mechanisms of regulation of human hepatic
      protein metabolism by fatty acids, and further study will be required to
      establish the nature of their influence in vivo.

PMID- 8998123
TI  - Glutathione regulates nitric oxide synthase in cultured hepatocytes.
AB  - OBJECTIVE: The authors determine the relationship between glutathione and nitric
      oxide (NO) synthesis in cultured hepatocytes. SUMMARY BACKGROUND DATA:
      Glutathione is a cofactor for a number of enzymes, and its presence is essential
      for maximal enzyme activity by the inducible macrophage nitric oxide synthase
      (iNOS), which produces the reactive nitric oxide radical. Hepatocytes contain
      substantial quantities of glutathione, and this important tripeptide is decreased
      in hepatocytes stressed by ischemia/reperfusion or endotoxemia. Endotoxemia also
      induces the synthesis of inflammatory cytokines that result in the production of
      nitric oxide from hepatocytes by iNOS, suggesting that hepatocytes may be
      attempting to synthesize nitric oxide at times when intracellular glutathione is
      reduced. METHODS: Hepatocytes were cultured with buthionine sulfoximine and 1,3
      bis(chloroethyl)-1-nitrosourea (BCNU) to inhibit glutathione. After exposure to
      cytokines, NO synthesis was assessed by supernatant nitrite levels, cytosolic
      iNOS enzyme activity, and iNOS mRNA levels. RESULTS: Inhibition of glutathione
      synthesis with buthionine sulfoximine or inhibition of glutathione reductase
      activity with BCNU inhibited nitrite synthesis. Both buthionine sulfoximine and
      BCNU inhibited the induction of iNOS mRNA, as detected by Northern blot analysis.
      Exogenous glutathione increased cytokine-stimulated iNOS induction, overcame the
      inhibitory effects of BCNU, and increased nitrite production by intact
      hepatocytes, induced hepatocyte cytosol, and partially purified hepatocyte iNOS.
      CONCLUSIONS: In cultured hepatocytes, adequate glutathione levels are required
      for optimal nitric oxide synthesis. This finding is predominantly due to an
      effect on iNOS mRNA levels, although glutathione also participates in the
      regulation of iNOS enzyme activity.

PMID- 8998128
TI  - Node-negative breast cancer patients exposed to unnecessary perioperative risk
      and increased long-term morbidity.

PMID- 8998127
TI  - Glutamine extraction by the gut is reduced in depleted [corrected] patients with
      gastrointestinal cancer.
AB  - OBJECTIVE AND SUMMARY BACKGROUND DATA: Glutamine is an important fuel for the
      intestinal mucosa. However, glutamine pools may become depleted in the cancer
      bearing host as a result of tumor consumption and diminished production due to
      nutritional depletion. As human data are lacking, the authors investigated
      glutamine extraction by different sites of the human intestine, including tumor
      and the potential relation with the degree of nutritional depletion. METHODS:
      Thirty-two patients with gastrointestinal malignancies were studied. Blood from
      an artery and veins draining jejunum, ileum, colon, or tumor were sampled.
      Depletion was estimated by the percentage ideal body weight. RESULTS: Fractional
      glutamine extraction rate in the jejunum was 24%, three times higher than in
      ileum and colon. Percentage ideal body weight correlated with arterial glutamine
      levels (r = 0.5275, p = 0.003). In addition, arterial glutamine concentrations
      were correlated with extraction in the ileum (r = -0.8411, p < 0.001). Colon
      containing tumor did not extract more glutamine than did nontumor-containing
      colon. CONCLUSIONS: Glutamine is a quantitatively more important substrate for
      the proximal intestine than for the distal gut. Nutritional depletion results in
      decreased arterial glutamine concentration, which in turn results in diminished
      extraction. Colon cancer does not function as a glutamine trap and does not
      contribute to glutamine depletion.

PMID- 8998129
TI  - Blood transfusions and local tumor recurrence in colorectal cancer: evidence of a
      noncausal relationship.

PMID- 8998130
TI  - Reported noncausal effect of blood transfusions on colorectal cancer recurrence.

PMID- 8998131
TI  - Complex metabolic studies in postoperative patients.

PMID- 8998132
TI  - Postoperative complications after splenectomy for hematologic malignancies.

PMID- 8998133
TI  - Serious traumatic injury and major burns.

PMID- 8998135
TI  - Laparoscopic aortofemoral bypass surgery performed in an animal model.

PMID- 8998134
TI  - Laparoscopic aortofemoral bypass in an animal model.

PMID- 8998136
TI  - Transperitoneal and retroperitoneal laparoscopic implantation of an aortofemoral
      prosthesis.

PMID- 8998137
TI  - Role of duodenal juice in the pathogenesis of gastroesophageal reflux disease.

PMID- 8998138
TI  - The reinvention of PET.

PMID- 8998139
TI  - Exploring Vietnam and its nuclear medicine.

PMID- 8998140
TI  - Imaging of dopamine transporters with iodine-123-beta-CIT and SPECT in
      Parkinson's disease.
AB  - The aim of the present study was to demonstrate the degeneration of the
      dopaminergic nigrostriatal pathway in Parkinson's disease by using the cocaine
      derivative [123I]beta-CIT (2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane or
      RTI-55) and SPECT and to relate the findings to the severity of the disease
      (Hoehn and Yahr scale, H/Y) and to clinical data such as motor score and
      activities of daily living. METHODS: Thirteen volunteers and 47 patients with
      idiopathic Parkinson's disease (PD) of H/Y Stage I-V (I:n = 16, II:n = 6, III:n =
      14, IV:n = 9, V:n = 2) were investigated. Acquisitions were performed 2, 4, 16,
      20 and 24 hr postinjection. ROIs were drawn over the striatum and the cerebellum.
      Specific beta-CIT binding was defined as striatal minus cerebellar binding. The
      ratio of specific over nondisplaceable binding (striatum/cerebellum-1) was
      determined as well as the percent deviation of this ratio from age-expected
      control values. RESULTS: The time-activity curve of striatal [123I]beta-CIT
      binding demonstrated a maximum around 20 hr postinjection in controls and a peak
      4 hr postinjection in PD patients. Ratios differed significantly between the two
      groups. A significant correlation existed between this ratio and clinical
      measures. Hemiparkinsonian patients revealed significantly diminished [123I]beta
      CIT binding not only contralateral to the clinically affected but also
      contralateral to the clinically unaffected side. [123I]beta-CIT binding showed a
      significant decrease in comparison to age-expected values ranging from 36% in H/Y
      stage 1 to 71% in H/Y stage V. CONCLUSION: The present study demonstrates that it
      is possible to visualize and quantify the degeneration of dopaminergic
      nigrostriatal neurons in PD using [123I]beta-CIT and SPECT with good correlation
      to clinical parameters.

PMID- 8998141
TI  - Regional stability of cerebral blood flow measured by repeated technetium-99m
      HMPAO SPECT: implications for the study of state-dependent change.
AB  - The replicability of resting state rCBF has implications for the analysis of
      cerebral activation protocols and the interpretation of rCBF in disease states.
      This study examined the stability of rCBF as measured by two resting state 99mTc
      HMPAO brain SPECT scans with an emphasis on examining the contribution of
      specific cerebral regions to within and between subjects variance. METHODS: Nine
      normal, medically healthy subjects underwent two 99mTc-HMPAO brain SPECT scans
      under identical conditions separated by 48 hr. A reference system and
      semiautomated computer ROI method was used to enable accurate alignment and
      cortical analysis of the two scans. RESULTS: Mean within-subject difference
      between Scans 1 and 2 was 2.8% (range 0%-7.8%) for the 36 cortical ROIs. The mean
      between-subject coefficient of variation was 10% (range 7%-15%) for these ROIs.
      Correlation analysis of rCBF pattern replication for all slice levels yielded a
      highly significant overall consistency of pattern within subjects (Pearson r =
      0.698, p = 0.0001). Variance component analysis revealed regional heterogeneity
      in between-subjects variance, with significantly greater variability found in
      frontal regions. The within-subject repeated measures variability was not
      significantly different across regions. CONCLUSION: Good within-subject 48-hr
      replicability indicates that individual resting state rCBF reflects fairly
      stable, subject-specific factors. This also justifies comparing state-dependent
      studies separated by a modest length of time. Although individual patterns of
      rCBF replicate well, the larger contribution of frontal regions to normal between
      subjects variance makes evaluating the frontal effects of disease or activation
      more difficult.

PMID- 8998142
TI  - Crossed-cerebellar diaschisis in cerebral infarction: technetium-99m-HMPAO SPECT
      and MRI.
AB  - We studied 26 patients with a single supratentorial infarction using 99mTc-HMPAO
      SPECT and MRI to investigate the phenomenon of crossed-cerebellar diaschisis
      (CCD). METHODS: From the total single-photon emission counts obtained from each
      cerebellar hemisphere, the percent difference between the contralateral (CCH) and
      ipsilateral (ICH) cerebellar hemispheres [delta %cbll = (CCH-ICH)/ ICH x 100] was
      calculated. Both SPECT (SVD) and MRI volume deficit (MVD) were measured to
      examine their relationship with CCD. RESULTS: A CCD was observed in 12 of the 26
      patients (46%) with cerebral infarction. There was no significant correlation
      between SVD and delta %cbll or MVD and delta %cbll in the patients with cerebral
      infarction. There were no significant differences in SVD and MVD between the
      patients with and without CCD. The frequency of CCD was significantly higher in
      the patients whose infarctions were in the frontoparietal lobes or the deep
      middle cerebral artery territory, including the basal ganglia and internal
      capsule (11/19) than in the patients whose infarctions were in other regions
      (1/7) (p = 0.048). The severely hemiparetic patients had a higher frequency of
      CCD and lower delta %cbll than the patients with milder or no hemiparesis
      (frequency, 5/5 compared with 6/18, p = 0.008; delta %cbll, -21.4% +/- 3.8%
      compared with -8.3% +/- 11.1%, p = 0.018). However, CCD also occurred in 5 of the
      14 patients without hemiparesis and was not seen in 5 of the 12 hemiparetic
      patients. None of the patients with CCD demonstrated the apparent clinical signs
      of cerebellar dysfunction. CONCLUSION: The location rather than the extent and
      severity of the lesion may be the major determinant for the occurrence and
      magnitude of CCD in patients with cerebral infarction. Our results also support
      the notion that CCD is a consequence of the interruption of the
      corticopontocerebellar pathway at the supratentorial level.

PMID- 8998143
TI  - Differentiating histologic malignancy of primary brain tumors: pentavalent
      technetium-99m-DMSA.
AB  - This study assessed pentavalent 99mTc-DMSA uptake in primary brain tumors and
      evaluated the relationship between retention and histologic malignancy. METHODS:
      SPECT images of the brain were obtained at 30 min and 3 hr after intravenous
      administration of approximately 555 MBq 99mTc(V)-DMSA in patients with brain
      tumors. Sixty studies were performed in 57 patients and 63 lesions were
      demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11
      astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios,
      retention ratio and retention index were calculated and compared with tumor
      histology and malignancy grade. RESULTS: Approximately 95% of both benign and
      malignant primary brain tumors were demonstrated by 99mTc(V)-DMSA SPECT images.
      False negative was noted in three cases. The early uptake ratios were closely
      related to the tumor vascularity but had no statistically significant difference
      in the tumor histology or histologic malignancy. The delayed uptake ratio,
      retention ratio and retention index were higher in the malignant tumors than the
      benign tumors. CONCLUSION: Technetium-99m(V)-DMSA washout from the tumor was
      highly dependent upon its histology and histologic malignancy. The delayed uptake
      ratio considerably reflected tumor histology and differentiated benign tumors
      from malignant tumors. The retention ratio and retention index significantly
      reflected tumor histology and histologic grade of primary brain tumors and
      clearly distinguished between benign and malignant tumors with statistically
      significant difference (p < 0.05). These results could suggest the clinical
      utility of 99mTc(V)-DMSA in imaging primary brain tumors and differentiating
      their histological malignancy grade noninvasively.

PMID- 8998144
TI  - Fasting improves discrimination of grade 1 and atypical or malignant meningioma
      in FDG-PET.
AB  - We investigated the use of PET with 2[18F]fluoro-2-deoxy-D-glucose (FDG) to
      discriminate between atypical or malignant and grade 1 meningiomas. The influence
      of fasting state and high-dose corticosteroid medication was analyzed
      retrospectively. METHODS: Preoperative PET scans of 75 patients with suspected
      diagnosis of intracranial meningioma were evaluated using standardized uptake
      values (SUV) and tumor-to-contralateral gray matter ratios (TGR) of FDG uptake.
      Fifty-one of 75 patients fasted before the PET scan, and 27 of 75 patients were
      studied under high-dose corticosteroid medication. Eighteen tumors had recurred.
      PET results were compared to histopathological grading. RESULTS: PET correctly
      identified 8/9 atypical or malignant meningiomas and 58/66 grade 1 meningiomas
      using TGR and a threshold of 1.05 in primary meningioma and 0.85 in tumor
      recurrence. This corresponds to a specificity of 0.88 for the detection of higher
      tumor grading. Specificity was significantly higher in fasting compared to
      nonfasting subjects (0.96 versus 0.73; p < 0.025). SUV quantification lead to a
      reduced specificity of 0.77 at the same level of sensitivity. The only false
      negative PET finding occurred in a recurrent meningioma, which had been operated
      on four times before. CONCLUSION: Overnight fasting before injection is needed to
      improve the diagnostic accuracy of FDG-PET for noninvasive metabolic grading of
      meningioma. Hyperglycemia in nonfasting patients and in diabetic patients may
      lead to overestimation of meningioma grading.

PMID- 8998145
TI  - Simplified quantification and reproducibility studies of dopamine D2-receptor
      binding with iodine-123-IBF SPECT in healthy subjects.
AB  - The purpose of this study was to assess the feasibility of a simplified SPECT
      scan protocol to quantify D2-receptor binding using [123I]iodobenzofuran (IBF)
      and to evaluate reproducibility of quantitative IBF-SPECT imaging without blood
      data. METHODS: Twenty healthy volunteers participated in the study, six had
      test/retest studies separated by 1 wk. Scans were acquired every 5 min for 180
      min using a triple-headed SPECT camera after a bolus injection of IBF (292 MBq).
      The receptor parameter was determined by using our previously proposed variation
      of graphical analysis that derives the distribution volume ratio (Rv = V3/V2)
      from multiple scan data without blood data. Rv' was determined from three 20-min
      scan data obtained at 0-20, 50-70 and 160-180 min postinjection and compared with
      Rv as determined from scans obtained at 0-180 min. RESULTS: The mean Rv' (2.93 +/
      0.59) underestimated the mean Rv (3.10 +/- 0.50) by 5%. The mean variability
      (mean percent absolute difference) between Rv' and Rv was low (10%) with
      excellent reliability (intraclass correlation coefficient, p = 0.90). The
      relationship between Rv' and Rv was linear (r = 0.95, p < 10(-5)). The mean
      test/retest Rv and mean test/retest Rv' were (3.19 +/- 0.70/3.18 +/- 0.80) and
      (3.16 +/- 0.81/3.01 +/- 0.94), respectively, and these measures were not
      significantly different between test/retest studies. The mean test/retest
      variability of Rv was low (5%) with excellent reliability (p = 0.98). In
      addition, the mean test/retest variability of Rv' was low (10%) with excellent
      reliability (p = 0.94). CONCLUSION: Three short (20 min) IBF-SPECT scans allowing
      for rest periods between scans permit reliable measurements of the dopamine D2
      receptor parameter V3/V2. Quantitative IBF-SPECT imaging without blood data is
      reliable and reproducible.

PMID- 8998146
TI  - "Yet there is method in't" (Shakespeare)

PMID- 8998147
TI  - Detection of coronary collaterals using dipyridamole PET myocardial perfusion
      imaging with rubidium-82.
AB  - This study evaluated the ability of dipyridamole PET myocardial perfusion imaging
      to detect coronary collaterals. A previous study showed an association between
      dipyridamole-induced coronary steal on PET imaging and the presence of coronary
      collaterals on angiography. METHODS: Dipyridamole PET myocardial perfusion
      imaging using 82Rb was performed in 45 patients who had recent coronary
      angiography. The stress/rest count ratio (rubidium activity with stress divided
      by activity at rest)-was used to express the change in regional tracer uptake
      with dipyridamole and was calculated manually and automatically. The accuracy of
      the stress/rest count ratio for detecting coronary collaterals was determined.
      RESULTS: A manual stress/rest count ratio < or = 0.80 identified coronary
      collaterals with 81% sensitivity, 92% specificity and 90% accuracy (p < 0.0001).
      An automated ratio < or = 0.80 had 90% sensitivity, 88% specificity and 90%
      accuracy (p < 0.0001). Vascular beds incorrectly identified by PET as having
      collaterals had an increased frequency of severe stenoses and abnormal wall
      motion. CONCLUSION: PET perfusion imaging using the stress/rest count ratio can
      serve as a unique imaging method to identify coronary collaterals noninvasively.

PMID- 8998148
TI  - Assessing coronary artery disease with dipyridamole technetium-99m-tetrofosmin
      SPECT: a multicenter trial.
AB  - Exercise 99mTc-tetrofosmin myocardial scintigraphy is as accurate as exercise
      201TI imaging. Thus far, no data are available on tetrofosmin imaging during
      pharmacologic stress. We evaluated the feasibility of using. 99mTc-tetrofosmin
      myocardial SPECT during vasodilation with dipyridamole for detecting coronary
      artery disease. METHODS: Sixty-four patients, enrolled in three centers in the
      U.S., underwent one-day dipyridamole/rest tetrofosmin SPECT. Coronary
      angiography, performed in 59 patients within 2 mo of the SPECT study, revealed
      normal coronary arteries or insignificant coronary stenosis in 11 patients and
      significant (> or = 50% luminal diameter stenosis) coronary stenoses in 48
      patients. RESULTS: Sensitivity and specificity of tetrofosmin SPECT for detecting
      coronary artery disease were 85% and 55%, respectively, in the overall population
      and 81% and 55% in patients without prior coronary artery bypass surgery. The
      overall sensitivity and specificity of tetrofosmin tomographic imaging for
      detection of individual coronary stenoses were 53% and 72%, respectively, in the
      overall population and 54% and 80% in the patients without prior coronary artery
      bypass surgery. CONCLUSION: One-day dipyridamole/rest 99mTc-tetrofosmin
      myocardial perfusion imaging is feasible and has a high sensitivity for detection
      of coronary artery disease.

PMID- 8998149
TI  - Myocardial iodine-123-metaiodobenzylguanidine images and autonomic nerve activity
      in normal subjects.
AB  - We studied the relationship between myocardial [123I]metaiodobenzylguanidine
      (MIBG) uptake and autonomic nerve activity in normal subjects. METHODS: MIBG
      scintigraphy and power spectral analysis (PSA) of heart rate variability were
      performed simultaneously in 15 normal subjects. Anterior planar images and SPECT
      images were taken at five and two points after the injection of [123I]MIBG,
      respectively. In 10 of 15 subjects, 201TI myocardial SPECT was performed
      immediately after MIBG scintigraphy. RESULTS: The heart/upper mediastinum MIBG
      uptake ratio in the planar image obtained at 240 min (r = 0.64, p < 0.01) and the
      washout rate of MIBG in the heart between 15 min and 240 min (r = 0.51, p < 0.05)
      showed significant correlation with the percentage of low frequency component of
      PSA (percent LF), an index of sympathetic nerve activity. Regional MIBG uptake in
      the inferior wall normalized by individual maximal uptake among all pixels was
      significantly correlated with the high frequency component of PSA, an index of
      parasympathetic nerve activity (r = -0.58, p < 0.05) and with mean R-R interval
      in a resting ECG (r = -0.82, p < 0.001) but did not correlate with percent LF,
      percent uptake of 201TI in the inferior wall or the liver/heart uptake ratio.
      CONCLUSION: These results indicate that myocardial MIBG uptake correlates with
      sympathetic nerve activity in normal subjects. Our data indicate that
      heterogeneous MIBG distribution in the left ventricle is a physiologic rather
      than artifactual phenomenon and may be related to vagal tone rather than
      sympathetic nerve activity.

PMID- 8998150
TI  - Assessment of left ventricular volume using ECG-gated SPECT with technetium-99m
      MIBI and technetium-99m-tetrofosmin.
AB  - We evaluated ECG-gated SPECT (g-SPECT) in the measurement of absolute left
      ventricular (LV) volume by comparing it with left ventriculography (LVG) and with
      cine-MRI. METHODS: Projection data from 31 patients were acquired with a three
      headed SPECT system in 12 min using a 64 x 64 matrix with 1.5 zoom (1 pixel =
      4.27 mm). The R-R interval from simultaneously acquired ECG was divided into
      eight frames. The end-diastolic and end-systolic volumes (EDV; ESV) and LV mass
      were assessed by an area-length method with manual delineation of the epi- and
      endocardial LV borders using midventricular vertical and horizontal long-axis
      images. The stroke volume, LVEF and cardiac output (CO) were generated from the
      EDV, ESV and heart rate during the study. The g-SPECT LV values were compared
      with those of LVG (25 patients) and cine-MRI (18 patients). RESULTS: The g-SPECT
      values correlated well with those from LVG (r = 0.83 to 0.92; p < 0.001) and cine
      MRI (r = 0.76 to 0.99; p < 0.001). The g-SPECT technique provides an assessment
      of LV volumes (EDV, ESV, stroke volume, LVEF, CO, LV mass). CONCLUSION: Despite
      potential problems that may cause inaccuracy and require improvements such as an
      accurate and reproducible automatic edge detection algorithm, g-SPECT has
      clinical utility in assessing global LV volumes and function.

PMID- 8998151
TI  - Comparison of technetium-99m-sestamibi scintimammography with contrast-enhanced
      MRI for diagnosis of breast lesions.
AB  - Scintimammography using 99mTc-sestamibi and contrast-enhanced MRI were performed
      to determine the diagnostic accuracy of either method in the diagnostic workup of
      patients suspicious for breast tumors. METHODS: Fifty-six patients (42 with
      indeterminate mammograms) underwent preoperative prone planar scintimammography
      and pre- and postcontrast-enhanced MRI. Visually determined signal increase after
      application of Gd-DTPA was compared with visually scored sestamibi uptake, and
      the diagnoses of both methods were correlated with the final histopathologic
      results. RESULTS: Overall, sensitivity and specificity of scintimammography for
      diagnosing breast cancer were 88% and 83%, respectively. In the subgroup of
      patients with indeterminate mammograms, sensitivity was 79% and specificity was
      83%. MRI readings provided a higher sensitivity (91% with respect to all patients
      and 89% with respect to patients with indeterminate mammograms), but a
      considerably lower specificity (52% in both groups) due to contrast-enhancement
      in different benign lesions. CONCLUSION: Due to its considerably higher
      specificity, scintimammography rather than MRI may be suitable to reduce the
      number of breast biopsies which yield benign results. Thus, this method may be
      suggested as the preferable tool in the diagnostic workup of patients with
      indeterminate mammographic findings.

PMID- 8998152
TI  - Technetium-99m-MIBI scintigraphy of thyroid nodules in an endemic goiter area.
AB  - Technetium-99m-methoxyisobutylisonitrile (MIBI) was introduced for myocardial
      imaging as an alternative to 201TI. According to biodistribution studies, MIBI
      also accumulates in the thyroid gland. The aim of this study was to find out
      which thyroid nodules retain MIBI and whether preoperative evaluation of
      malignancy is possible. METHODS: Single injection, dual-phase (30 min and 2 hr)
      thyroid scintigraphy with 99mTc-MIBI was performed on 62 patients who showed a
      cold nodule on previously performed 99mTc scintigraphy. MIBI scans were
      considered positive if there was a clear tracer retention in the late 120-min
      image compared to the early 30-min image. Sonographic examination and fine-needle
      aspiration biopsy, guided by ultrasonography, was also done on each patient. In
      the following days and weeks, all patients underwent surgery. RESULTS:
      Histopathological diagnoses revealed a total of 12 thyroid carcinomas, five were
      MIBI positive and seven MIBI negative. Out of 27 patients with thyroid adenomas
      (nine microfollicular, ten follicular, eight oxyphilic), 18 were MIBI positive
      and nine MIBI negative. There was no MIBI retention on the scans of 22 patients
      with degenerative changes in the goiter and the one with Hashimoto's disease.
      CONCLUSION: These results indicate that MIBI accumulation and retention is not
      specific for thyroid malignancy. Indeed, all evidence points to the fact that a
      positive MIBI scan is more likely to indicate thyroid adenoma than a malignant
      tumor.

PMID- 8998153
TI  - Ventilation scintigraphy of the middle ear.
AB  - In this study, an attempt was made to administer radioactive gas into the
      tympanic cavity to measure initial gas trappings as well as clearance from the
      middle ear to evaluate eustachian tube function. METHODS: Twenty-eight patients
      were administered 50 MBq 133Xe gas. Three different methods for gas application
      were tested: (a) direct injection through a tympanostomy tube in two patients,
      (b) administration through a nasopharyngeal catheter combined with Valsalva
      maneuvers in six subjects without middle ear dysfunction and (c) insufflation
      into the pharyngeal space through a nose olive performed in 12 patients with
      normal eustachian tube function and in eight patients with one-sided tube
      dysfunction. RESULTS: All three approaches were successful in visualizing middle
      ear ventilation, demonstrating tracer trapping within the tympanic cavities in 20
      of 28 patients. Semiquantitative evaluation by region of interest techniques
      revealed a left-to-right uptake ratio of 48.4%-51.6% in 13 patients without tube
      dysfunction. Five patients with one-sided tube dysfunction showed a significantly
      lower median uptake of 31.6% (p = 0.01). The clearance half-lives ranged from 9
      to 283 min in normal subjects and 37-64 min in patients with one-sided tube
      malfunction, demonstrating no statistically significant difference between the
      two groups and a trend towards increased washout in patients with tympanic
      dysfunction. CONCLUSION: Middle ear ventilation scintigraphy with 133Xe through a
      nose olive is an easy-to-perform test to evaluate eustachian tube function and
      has a success rate of about 70%, thus, reflecting the complex physiological
      mechanisms involved.

PMID- 8998154
TI  - Prestenotic bronchial radioaerosol deposition: a new ventilation scan sign of
      bronchial obstruction.
AB  - This study was performed to assess the diagnostic usefulness of aerosol
      ventilation scanning in bronchial obstruction and bronchial stenosis. METHODS:
      Seven patients of bronchial obstruction and one patient with stenosis were
      studied. In each patient, obstruction was confirmed by bronchography,
      bronchoscopy and/or CT scan. Ventilation scanning was performed using the 99mTc
      phytate aerosol generated by a BARC jet nebulizer. Scan manifestations were
      assessed in correlation with those of plain chest radiography, bronchography, CT
      scan and/or bronchoscopy. RESULTS: In every patient, the ventilation scan showed
      characteristic intense aerosol deposition in a short, slightly dilated, clubbed,
      bronchial segment immediately proximal to obstruction or stenosis. Typically, it
      was accompanied by a distal airspace deposition defect. CONCLUSION: Intense,
      segmental, bronchial aerosol deposition with distal lung defect was a specific
      finding of bronchial obstruction and stenosis. The sign was especially useful
      when obstruction was obscured by the associated, bizarre lung disease and in a
      small bronchus.

PMID- 8998155
TI  - Background subtraction in technetium-99m-MAG3 renography.
AB  - Correction represents a potential source of error in estimating split renal
      function and camera-based clearances. The purpose of this study was to determine
      which of five background options and four time intervals was associated with the
      least error for 99mTc-mercaptoacetyltriglycine (MAG3). METHODS: Fifteen single
      kidney patients were imaged supine after 111-370 MBq (3-10 mCi) 99mTc-MAG3
      injection. A phantom kidney was drawn on the 2-3-min images, approximately equal
      in size to the solitary kidney and used for all time intervals. Counts in the
      phantom and native kidneys were calculated using manual inferior and lateral
      regions of interest (ROIs), automated elliptical and perirenal background ROIs
      and no background correction at various time intervals (1-2, 1-2.5, 1.5-2.5 and 2
      3 min) postinjection. With optimal background correction, counts and the relative
      function in the phantom kidney should be zero. The error was measuring by
      estimating both the relative function and absolute function expressed as the
      percent injected dose in the phantom kidney. RESULTS: The percent injected dose
      in the phantom kidney as well as the error in measuring relative function were
      significantly greater than zero for the inferior background correction and the no
      background correction options at all time intervals, p < 0.05. The percent dose
      in the kidney and the error associated with the lateral, elliptical and perirenal
      ROIs were not significantly different from zero. CONCLUSION: Regardless of time
      interval, the greatest error was associated with no background correction. The
      inferior ROI consistently underestimated the background correction and probably
      should not be used for 99mTc-MAG3. There was no significant difference between
      errors generated using the lateral and automated ROIs, although automated ROIs
      are probably more reproducible for sequential studies.

PMID- 8998156
TI  - Evaluation of fulminant hepatic failure by scintigraphy with technetium-99m-GSA.
AB  - We evaluated the usefulness of hepatic receptor imaging with 99mTc
      diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) to
      establish the diagnosis and prognosis of fulminant hepatic failure (FHF).
      METHODS: Of the 20 patients, 8 had acute hepatitis and 12 had FHF. Computer
      acquisition of gamma-camera data started just before the injection of 185 MBq
      99mTc-GSA and stopped 20 min later. Time-activity curves for the heart and liver
      were generated from regions of interest (ROIs) for the whole liver and
      precordium. A receptor index was calculated by division of the radioactivity of
      the liver ROI by that of the liver plus heart ROIs 15 min after the injection. An
      index of blood clearance was calculated by division of the radioactivity of the
      heart ROI at 15 min by that of the heart ROI 5 min after the injection. RESULTS:
      The receptor index was less than 0.83 in all patients with FHF, but it was more
      than 0.83 in all patients with acute hepatitis. The index of blood clearance was
      more than 0.72 in all patients with FHF but less than 0.72 in all patients with
      acute hepatitis. All six survivors of FHF had receptor indices of 0.58 or more,
      but in five of the six patients who later died, the receptor index was 0.58 or
      less. The index of blood clearance was 0.85 or less in all survivors but 0.85 or
      more in the same five patients who later died. CONCLUSION: Hepatic receptor
      imaging with 99mTc-GSA facilitated the evaluation of hepatic function reserve and
      was useful in establishing the diagnosis and prognosis of FHF.

PMID- 8998157
TI  - Brain perfusion after treatment of childhood acute lymphoblastic leukemia.
AB  - Children with acute lymphoblastic leukemia (ALL) have impairment in their
      neuropsychological functioning and morphological changes in their brain after
      cranial irradiation and chemotherapy. The aim of this study was to identify
      possible brain perfusion defects caused by different types of treatment and their
      association with abnormalities in cerebral MRI and neuropsychological and
      clinical neurological findings. METHODS: Twenty-five consecutive children with
      ALL at the cessation of chemotherapy or after 1 yr were included. All of the
      children were given intravenous and intrathecal methotrexate for central nervous
      system therapy, 13 of them received cranial radiation therapy. Brain SPECT,
      cerebral MRI, clinical neurological and neuropsychological evaluations were
      performed. RESULTS: Eleven of the 25 patients (44%) had brain perfusion defects
      in SPECT, eight of whom were treated with chemotherapy alone, and three received
      cranial irradiation. Two patients had small bilateral white matter changes on
      MRI; their brain SPECT scans were abnormal, although the findings were not
      related. Impairment of neuropsychological functioning was found in 86% of the
      patients tested. No significant difference between the patients with abnormal and
      normal SPECT were found. Those patients with abnormal SPECT were younger than
      those with normal SPECT and had received more frequent intravenous methotrexate
      infusions. CONCLUSION: Brain SPECT detected perfusion defects that had occurred
      after treatment for childhood ALL. These defects may be related to frequent
      administration of a combination of intravenous and intrathecal methotrexate
      and/or young age.

PMID- 8998158
TI  - Diagnostic test comparisons in patients with deep venous thrombosis.
AB  - New diagnostic modalities are often judged relative to accepted standard
      procedures. These comparisons are influenced by the accuracy of the standard test
      and the prevalence of disease in the study population. We evaluated the
      importance of these factors in the assessment of antifibrin scintigraphy when
      used to detect deep venous thrombosis. METHODS: Scintigraphy is compared to
      contrast venography in two populations of patients with different disease
      prevalence. We calculate the sensitivity and specificity by limb site (calf,
      knee, thigh) and the overall diagnosis for each modality. The sensitivity and
      specificity results obtained using venography as a gold standard are compared to
      those obtained using a maximum likelihood statistical procedure that does not
      require comparison to a standard test. RESULTS: A significant variation in the
      apparent sensitivity, specificity and accuracy is found for antifibrin
      scintigraphy as related to limb site, disease prevalence and use of a gold
      standard. The value of antifibrin scintigraphy sensitivity (84.7%) and
      specificity (75.8%) predicted by the maximum likelihood analysis are
      substantially higher than those obtained from the estimates based on the use of
      venography as a gold standard for both high and low disease prevalence
      populations. The sensitivities and specificities of antifibrin scintigraphy
      (84.7% and 75.8%, respectively) and venography (71.7% and 80.7%, respectively)
      are comparable for the combined study group of 268 patients. CONCLUSION: To
      obtain unbiased evaluations of a new diagnostic modality, it is essential to take
      into account the errors of the standard reference test and disease prevalence in
      the study population. The results of our analysis suggest that it may not be
      appropriate to use contrast venography as a gold standard in the assessment of
      new diagnostic imaging procedures for DVT.

PMID- 8998159
TI  - Oxygen-15-water PET assessment of muscular blood flow in peripheral vascular
      disease.
AB  - To assess quantitatively regional nutritive muscular blood flow in patients with
      peripheral vascular disease (PVD), we evaluated the utility of PET with 15O
      water. METHODS: Eight healthy volunteers and 16 patients with angiographically
      proven PVD were studied. Regional blood flow of the calf was measured with 15O
      water PET during rest, after intra-arterial infusion of prostaglandin E1 and
      during ergometry. The studies were quantified using a one tissue compartment
      model. RESULTS: Normalized mean tracer uptake from 15-60 sec correlated closely
      (r = 0.98) with absolute blood flow. Scan times longer than 90 sec were required
      to determine blood flow reliably. The flow values were overestimated by 2% if
      arterial blood volume was neglected or if the input function delay was corrected
      globally for parametric imaging. Mean blood flow of calf muscles at rest did not
      differ significantly between patients (0.017 +/- 0.006 ml/min/ml) and control
      subjects (0.018 +/- 0.010 ml/min/ml). In PVD patients, blood flow increased by
      100% after intra-arterial infusion of PGE1 in the respective leg. In the control
      subjects, average flow increased by a factor of six during exercise. The increase
      was more pronounced in the extensor muscles (0.182 +/- 0.031 ml/min/ml) than in
      flexor muscles (0.121 +/- 0.045 ml/min/ml). Due to the specific type of
      ergometry, superficial flexors exhibited higher flow values than the profound
      ones. CONCLUSION: PET with 15O-water enables reliable determination of regional
      nutritive skeletal muscle blood flow for research and clinical applications in
      patients with PVD.

PMID- 8998161
TI  - Incidence of subclavian vein thrombosis detected during first-pass phase of
      radionuclide angiocardiogram.
AB  - A 79-yr-old woman with asymptomatic subclavian vein thrombosis associated with
      transvenous pacemaker electrode and congestive heart failure is reported. The
      subclavian thrombosis was discovered accidentally from the first-pass
      radionuclide angiogram that is routinely performed with the intravenous bolus
      injection of the radiopharmaceutical for a gated blood-pool study. It
      demonstrated venous obstruction at the level of the subclavian vein and abnormal
      collateral circulation over the chest wall consistent with subclavian thrombosis.
      This case report and literature review demonstrates the importance of performing
      first-pass radionuclide cardioangiography routinely before multigated blood-pool
      studies in patients with pacemakers.

PMID- 8998160
TI  - FDG-PET evaluation of retroperitoneal metastases of testicular cancer before and
      after chemotherapy.
AB  - We describe a patient whose primary tumor was a testicular teratocarcinoma
      predominantly composed of embryonal carcinoma. Before chemotherapy, the
      retroperitoneal metastases demonstrated heterogeneous, increased glucose
      metabolism as measured by 2-[18F]fluoro-2-deoxy-D-glucose and PET (FDG-PET).
      After chemotherapy, FDG uptake was reduced to normal values despite increased
      tumor volume. Histology revealed a pure mature teratoma. This observation
      suggests that further studies are needed to determine whether tumor
      differentiation of testicular teratocarcinoma metastases can be assessed by
      measuring glucose metabolism.

PMID- 8998162
TI  - Volume-dependent pulmonary aspiration of a swallowed radionuclide bolus.
AB  - The radionuclide salivagram was introduced as a simple physiologic technique to
      document the aspiration of saliva in patients with chronic lung disease. We
      previously reported positive studies to be prevalent in patients with
      neuromuscular incoordination, as with cerebral palsy, or after surgery involving
      the upper airway. Many patients referred for a salivagram, however, have an
      apparent intact swallowing mechanism and are better challenged with a tagged
      bolus.

PMID- 8998163
TI  - Pre-clinical evaluation of technetium-99m platelet receptor-binding peptide.
AB  - P748 is a dimeric peptide which incorporates two high affinity GPIIb/IIIa
      receptor-binding domains and a novel 99mTc binding sequence, which provides the
      platelet imaging agent 99mTc-P748. The aim of this study was to evaluate 99mTc
      P748 preclinically for use as a hot spot scintigraphic thrombus imaging agent.
      METHODS: Technetium-99m-P748 was prepared by either a ligand exchange or a one
      vial kit. The oxorhenium congener, [ReO]P748, was prepared by ligand exchange
      from Bu4NReOBr4. The binding of P748 peptide and [ReO]P748 to GPIIb/IIIa
      receptors on activated platelets was assessed by their inhibition of ADP
      stimulated human platelet aggregation in platelet rich plasma (PRP). The
      localization of 99mTc-P748 in deep vein and pulmonary thrombi was assessed in a
      canine thrombosis model and the biodistribution of 99mTc-P748 was determined in
      rats. RESULTS: P748 peptide inhibited the aggregation of human platelets in PRP
      by 50% at a concentration (IC50) of 28 nM and [ReO]P748 had an IC50 of 36 nM
      showing the high in vitro receptor binding affinity of both the peptide and its
      rhenium complex (and by analogy its technetium complex). Technetium-99m-P748 was
      readily prepared at room temperature in 15 min in > or = 90% radiochemical yield
      and purity and provided definitive images of femoral vein thrombi within 20 min
      and pulmonary thrombi, within 1 hr in the canine model. Femoral vein thrombus-to
      blood and thrombus-to-muscle ratios at 4 hr averaged 6.7 and 46, respectively.
      Pulmonary thrombus-to-blood and thrombus-to-normal lung ratios at 4 hr averaged
      29 and 27, respectively. Dog and rat studies both showed rapid clearance of the
      radiotracer from the blood and with no significant hepatobiliary excretion but
      with notable early kidney retention. CONCLUSION: The combination of high in vitro
      receptor-binding affinity, high thrombus uptake and definitive in vivo images of
      both femoral vein and pulmonary thrombi show that 99mTc-P748 has considerable
      potential as a clinical imaging agent for the detection of venous
      thromboembolism.

PMID- 8998164
TI  - Zirconium-labeled monoclonal antibodies and their distribution in tumor-bearing
      nude mice.
AB  - A method to label monoclonal antibodies (MAbs) with 88Zr and 89Zr has been
      developed and tested on the MAbs 323/A3 and E48. METHODS: The bifunctional
      chelating agent desferal (Df) was linked through a thioether bond to the MAbs.
      Labeling was accomplished by addition of the premodified antibodies to isolated
      Zr. The retention of the in vivo behavior of the MAbs was determined by comparing
      the biodistribution of 88Zr-labeled MAbs with those of 123I and 99mTc in mice
      bearing tumor xenografts. RESULTS: The labeling was simple and the yields were
      high (above 90%). The obtained conjugates retained their immunoreactivity (>
      80%). The blood clearance and biodistribution of Zr-labeled MAbs resembled those
      of the reference conjugates. The Zr-Df-MAb conjugates showed a specific tumor
      accumulation. Zirconium-89-labeled 323/A3 could be visualized with a PET camera.
      The absence of large amounts of Zr present in the bone pointed to a good in vivo
      stability of the Zr-Df-MAb conjugates. CONCLUSION: This method is well suited for
      labeling MAbs with Zr isotopes. Using 89Zr, the biodistribution of the
      radioimmunoconjugate can easily be visualized with a PET camera.

PMID- 8998166
TI  - Pharmacokinetics of iodine-123-IMBA for melanoma imaging.
AB  - The development of an effective radiopharmaceutical with affinity for malignant
      melanoma has been a research goal for some time. The early detection of melanoma
      metastases would greatly improve the therapy outcome for this disease. This
      article describes the synthesis of radioiodinated IMBA, N-(2-diethylaminoethyl)-3
      [123I/131I]iodo-4-methoxybenzamide 8, its organ distribution, its comparison with
      BZA and other benzamides, and demonstrates the scintigraphic efficacy of the
      title compound with three melanoma patients. METHODS: The syntheses and
      radioiodination of eight benzamide derivatives are described. After intravenous
      injection into C57B16-mice subcutaneously transplanted with B16 melanoma, the
      organ distribution of the respective benzamides were investigated at 1 and 6 hr.
      n-octanol/phosphate buffer partition coefficients. The wholebody retention,
      erythrocyte and serum protein bound fractions of radioiodinated benzamides were
      measured. RESULTS: While structural changes in the amide substituents of N-(2
      dialkylaminoalkyl)-4-iodobenzamides 2-7 resulted in no improvement in organ
      distribution compared with BZA, the 3-iodo-4-methoxyphenyl form of IMBA showed
      high melanoma uptake with significantly higher melanoma/nontarget tissue ratios.
      Compared with BZA the average ratio improved after 1 hr by a factor of eight and
      was still four times better after 6 hr. BZA and IMBA exhibit almost identical n
      octanol/ phosphate buffer partition coefficients, however, IMBA has a faster
      urinary excretion facilitated by a lower affinity to erythrocytes and serum
      proteins; this could explain the improved tissue partinioning observed.
      Scintigraphy of patients with melanoma metastases confirmed the promising
      characteristics derived from the animal studies. CONCLUSION: Due to rapid
      background clearance and high melanoma affinity, IMBA showed high tumor contrast
      already at 4 hr after injection which makes it a promising new
      radiopharmaceutical for the scintigraphic detection of melanoma metastases.

PMID- 8998165
TI  - Fluorine-18-FPCT: a PET radiotracer for imaging dopamine transporters.
AB  - Fluorine-18-labeled 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3
      fluoropropyl) nortropane (FPCT) has been synthesized as a new dopamine
      transporter imaging agent. METHODS: Fluorine-18 was introduced into 2 beta
      carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane by
      preparation of 1-[18F]fluoro-3-iodopropane followed by alkylation of 2 beta
      carbomethoxy-3 beta-(4-chlorophenyl)nortropane. RESULTS: Tissue distribution
      studies in rats with [18F]FPCT showed high striatal uptake (0.70% dose/g at 60
      min; 0.38% dose/g at 120 min) and good striatal-to-cerebellum ratios (5.5 at 60
      min; 6.2 at 120 min). Imaging studies in rhesus monkeys (n = 2) with [18F]FPCT
      showed high uptake and retention in the putamen (P) (P = 0.03%-0.12% dose/g; at
      115 min) and good putamen-to-cerebellum ratios of 3.40-3.43 at 115 min. Plasma
      metabolites were analyzed in rhesus monkeys (n = 2) by ether extraction and HPLC.
      The radioactivity in the ether-extractable fraction displayed a single peak that
      corresponded on HPLC to unmetabolized authentic FPCT. CONCLUSION: These results
      suggest that [18F]FPCT is an excellent candidate for PET imaging of dopamine
      transporters.

PMID- 8998168
TI  - Interaction of technetium-99m-N-NOET with blood elements: potential mechanism of
      myocardial redistribution.
AB  - Technetium-99m-N-NOET is a new 99mTc-labeled, neutral cardiac perfusion imaging
      agent which has been shown to undergo apparent redistribution in animal models
      and in humans. The purpose of this study was to investigate the interaction of
      99mTcN-NOET with red blood cells (RBCs) and to determine the effects of these
      interactions on myocardial uptake and clearance of 99mTcN-NOET. METHODS: After
      bolus administration, myocardial 99mTcN-NOET clearance was monitored for 1 hr
      using a sodium iodide detector in 22 isolated, buffer-perfused rat hearts. Hearts
      were perfused as follows: seven controls with Krebs-Henseleit (KH) buffer (Group
      1), five hearts with KH containing RBCs (Group 2), five hearts with KH containing
      RBCs and albumin (Group 3), five hearts with KH containing RBCs and dextran
      (Group 4). In a separate protocol, RBCs were incubated in 99mTcN-NOET and then
      perfused through five hearts (Group 5). RESULTS: Technetium-99m-N-NOET myocardial
      uptake (%ID) was significantly lower in all RBC groups (RBCs = 5.0% +/- 1.7%;
      RBCs + albumin = 8.2% +/- 2.1%; RBCs + dextran = 4.0% +/- 0.8%; incubated RBCs =
      8.8% +/- 1.5%) compared with controls (72.2% +/- 2.8%; p < 0.05). Retention
      (99.4% +/- 0.6%) was near linear in the KH control group with virtually no
      fractional clearance at 60 min. Retention in groups whose perfusates contained
      RBCs (RBCs = 62.2 +/- 4.2%; RBCs + albumin = 29.9 +/- 4.3%; RBCs + dextran = 69.3
      +/- 3.6%) were all significantly lower than control. Addition of albumin to RBC
      perfusate resulted in significantly lower retention (29.9% +/- 4.3%; p < 0.01)
      than was observed in RBC perfusate alone (62.2% +/- 4.2%). Substitution of
      dextran for albumin produced retention similar to RBCs alone (69.3% +/- 3.6%; p =
      ns). In a separate protocol, RBC binding of 99mTcN-NOET was high (64.4% +/- 8.6%)
      in triple-washed RBCs. Technetium-99m-N-NOET bound to RBCs was subsequently
      extracted from red cells by the myocardium when those cells were infused into
      hearts. CONCLUSION: Technetium-99m-N-NOET has high binding affinity to blood
      elements and transfers bidirectionally between myocardium and blood. The
      interaction of 99mTcN-NOET with blood elements represents a potential mechanism
      of redistribution.

PMID- 8998167
TI  - Tumor imaging with technetium-99m-labeled hydrazinonicotinamide-Fab' conjugates.
AB  - This study compares the in vivo properties of direct versus indirect 99mTc
      labeling for two Fab' fragments from antibodies that recognize tumor-associated
      antigens. METHODS: Fab' fragments of two IgG2a monoclonal antibodies were either
      radiolabeled directly or via the linker bromoacetyl hydrazinonicotinamide
      hydrobromide (BAHNH) conjugated site specifically at protein thiols. A thiol
      assay was used to determine the number of thiols in the Fab' and to monitor their
      consumption during conjugation with BAHNH. Both preparations were labeled to >
      95% incorporation of 99mTc, with the isotope tracking the single 50 kD absorbance
      peak seen on size-exclusion HPLC. The labeled preparations were tested in tumor
      bearing and control mice, with dissections at 4 and 24 hr and gamma scintigraphy
      of the tumor-bearing mice. RESULTS: The major difference between the two labeled
      preparations for either antibody fragment was the greater accumulation of isotope
      in the tumor for the indirectly labeled preparations. This increase ranged from
      1.5- and 2.7-fold at 4 hr to 2.6- and 3.2-fold at 24 hr for the two antibodies,
      respectively. Since blood clearance was similar for the two labeling methods, the
      higher tumor accumulation with the indirectly labeled fragments resulted in
      higher tumor to blood ratios. Tumors could be imaged with both antibodies with
      either type of labeling with greater clarity and sensitivity at the 24 hr time
      point. CONCLUSION: While both labeling methods resulted in tumor detection
      through imaging, the images obtained with the indirectly labeled antibody
      fragments were more easily visualized due to the combination of higher
      radioisotope accumulation in the tumor and similar blood clearances compared to
      the direct labeled fragment.

PMID- 8998170
TI  - Nonuniform collimator sensitivity: improved precision for quantitative SPECT.
AB  - Attenuation of photons degrades both the accuracy and the precision of SPECT
      images; attenuation correction algorithms correct the bias but cannot improve
      precision. Increased noise due to photon attenuation is most pronounced in
      regions deep in solid body sections, such as the brain and abdomen. We have
      quantified the degradation in performance in several estimation tasks that can be
      attributed to photon attenuation and determined the degree to which performance
      might be improved by a collimator with a nonuniform sensitivity profile. METHODS:
      The analysis used ideal-observer models of performance in tasks involving
      estimation of the activity and size of a focal lesion. The models were based on
      the Cramer-Rao lower bound on the variance with which lesion activity and size
      can be estimated by an unbiased procedure. To quantify the effects of
      attenuation, values of the Cramer-Rao bound were calculated for each estimation
      task as a function of location of the lesion in circularly-shaped attenuators of
      10- and 20-cm radii, with and without attenuation. Values of the bound were also
      determined for two nonuniform sensitivity profiles, one of which was designed to
      equalize (or nearly equalize) task performance throughout the image. RESULTS: For
      99mTc, photon attenuation increased the variance of the estimates by factors of
      up to 4.5 for the 10-cm radius attenuator and up to 20.0 for the 20-cm radius
      attenuator. A collimator with a nonuniform sensitivity function reduced variance
      by factors of up to 1.8 for the 10-cm radius attenuator and up to 2.8 for the 20
      cm radius attenuator. These gains in estimation performance were insensitive to
      the imaging task and to deviations from the assumed attenuator size and shape.
      CONCLUSION: Performance in estimation tasks using images from SPECT systems with
      uniform sensitivity collimators is considerably lower than the theoretical
      optimum. We have derived a sensitivity function, realizable using existing
      technology, that improves performance substantially.

PMID- 8998169
TI  - SPECT imaging of dopamine transporter sites in normal and MPTP-Treated rhesus
      monkeys.
AB  - Parkinson's disease is characterized by degeneration of dopamine (DA) neurons and
      their terminals. Since these neurons contain dopamine transporters (DAT),
      radioligands that bind to these sites are promising radiopharmaceuticals for
      diagnosis and therapeutic monitoring of disease progression. We evaluated [123I]
      2 beta-carbomethoxy- 3 beta-(4-fluorophenyl)-N-(1-iodoprop-1-en-3-yl)nortropane
      ([123I]IACFT) for SPECT imaging in an MPTP model of parkinsonism. METHODS: Three
      rhesus monkeys were imaged before and at 1 and 2 mo after treatment with MPTP.
      The SPECT results were correlated with motor behavior and PET imaging with [11C]
      2 beta-carbomethoxy-3 beta-aryltropane ([11C]-CFT). Also, biodistribution was
      measured by planar imaging. RESULTS: In normal animals, striatal accumulation of
      radioactivity was rapid and peaked within 30 min. Striatal accumulation of
      [123I]IACFT was nearly completely displaceable with unlabeled CFT (1 mg/kg) but
      was not affected by a similar dose of the serotonin (5-HT) transport inhibitor,
      citalopram. The striatal to cerebellar ratio measured at 30 min, after injection
      of [123I]IACFT was significantly higher (p < 0.01) than with [11C]CFT;
      approximately 6; 1 versus approximately 2.5; 1. After MPTP treatment this ratio
      decreased to 1.02:1 with IACFT and 1.23:1 with [11C]CFT. Blood clearance of
      [123I]IACFT was rapid with a terminal t1/2 of approximately 30 min. HPLC of
      plasma samples demonstrated that the concentration of intact ligand decreases
      rapidly, approaching zero by 60 min. Low levels of accumulation were measured in
      extracranial tissues. CONCLUSION: These results demonstrate that [123I]IACFT is
      an excellent SPECT ligand for dopamine transporter sites that combines the
      critical characteristics of: (a) high striatal to cerebellar ratios, (b) high
      selectivity for dopamine versus 5-HT transporter sites, (c) convenient
      preparation at high-specific activity and radiochemical purity and (d) a striatal
      localization rate that is well matched to the physical t1/2 of 123I.

PMID- 8998171
TI  - Scatter and attenuation correction in technetium-99m brain SPECT.
AB  - We propose a practical method for scatter and attenuation compensation in 99mTc
      ECD brain SPECT using a simultaneous emission CT (ECT) and transmission CT (TCT)
      acquisition system that includes the following major components: (a) triple
      headed SPECT gamma camera equipped with fanbeam collimators; (b) external line
      sources containing 99mTc placed at the focal lines of the collimators; and (c)
      scatter correction by the triple-energy-window (TEW) method. METHODS: Projection
      images were obtained over a 360 degrees rotation scan. After acquisition, scatter
      correction was performed using the TEW method, which corrected scattered photons
      pixel by pixel in the projection data. Scatter-corrected ECT images were
      compensated for attenuation using the TCT images with Chang's iterative method,
      and were converted to activity concentration (kBq/ml) images by obtaining a cross
      calibration scan. After validating this method with phantom studies, it was
      applied to clinical brain imaging using a combination of 925 MBq 99mTc-ECD as a
      radiopharmaceutical and 222 MBq 99mTc as an external source. ECT and TCT data
      were acquired separately or simultaneously. RESULTS: SPECT quantification and
      image quality were improved by performing this correction. The activity
      concentration images obtained with the simultaneous acquisition were almost
      identical to those obtained with the separate acquisition. CONCLUSION: This
      method was clinically practical and cost-effective for reconstructing
      quantitative 99mTc brain SPECT images.

PMID- 8998172
TI  - Physical properties and use of pertechnegas as a ventilation agent.
AB  - Pertechnegas, a variant of technegas, produces similar ventilation images with a
      much increased clearance rate. This work aims to determine the properties of
      pertechnegas and its use as a ventilatory agent. METHODS: Fourteen men and 11
      women were scanned for PE, after pertechnegas ventilation. Six were reimaged with
      technegas within 1 wk. Studies were reported according to PIOPED criteria.
      Pertechnegas samples were analyzed by transmission electron microscopy (TEM),
      cascade impaction (CI), aerosol mobility analysis (AMA), Fourier transform mass
      spectrometry (FTMS), x-ray photoelectron spectroscopy (XPS), paper strip (PC) and
      gas chromatography (GC). RESULTS: Post-test probabilities were normal in 5, low
      in 8, high in 5 and indeterminate in 7. There were 15 Grade 1, 6 Grade 2 and 4
      Grade 3 studies. All Grade 3 patients had FEV1 < 1.5 liters, 3 with rates < 1.0
      liter. Patients with high probability had proven deep venous thrombosis in three
      by venography and in one by doppler. TEM identified 0.3 micron salt particles. CI
      demonstrated a 7-min time to half clearance from the chamber for particles in the
      < 0.1 micron range. AMA indicated all particles were < 0.032 micron when salt was
      excluded. Pertechnegas behaves in PC as pertechnetate, GC demonstrated CO levels
      below 516 ppm. CO2 concentrations were 0.146 +/- 0.0009%. FTMS found molecular
      pertechnetate species including 99TcO3(OH)+, Na99TcO3(OH)3+ and Na99TcO3(OH)3+.
      XPS confirmed that these Tc species exist in oxidation state +7. CONCLUSION:
      Comparison with technegas images in the follow-up group proved equivalent in the
      first five views, but indistinct lung boundaries and a high background activity
      characterized the final anterior images. The active component of pertechnegas is
      molecular pertechnetate.

PMID- 8998174
TI  - Androgen and vitamin D receptor gene polymorphisms: the long and short of
      prostate cancer risk.

PMID- 8998173
TI  - Harnessing the power of antisense technology for combination chemotherapy.

PMID- 8998175
TI  - Photodynamic therapy expands its horizons.

PMID- 8998176
TI  - Bisphosphonates spearhead new approach to treating bone metastases.

PMID- 8998177
TI  - NPCC unifies prostate cancer advocates.

PMID- 8998178
TI  - Gene therapy group agrees to smaller size, less authority.

PMID- 8998179
TI  - For women smokers, the gender gap is narrowing.

PMID- 8998180
TI  - "Sweet sixteen" drugs blur line between treatment, prevention.

PMID- 8998181
TI  - Treatment of Philadelphia leukemia in severe combined immunodeficient mice by
      combination of cyclophosphamide and bcr/abl antisense oligodeoxynucleotides.
AB  - BACKGROUND: Philadelphia cells are human chronic myelogenous leukemia (CML) cells
      that contain the BCR/ABL oncogene (a fusion of the BCR and ABL genes). Selective
      eradication of these cells in vitro can be achieved by combined treatment with
      antisense phosphorothioate oligodeoxynucleotides ([S]ODNs) specifically targeted
      to this oncogene (bcr/abl [S]ODNs) and a suboptimal (for use as a single agent)
      dose of mafosfamide (the in vitro active form of cyclophosphamide). PURPOSE: We
      evaluated the ability of bcr/abl antisense [S]ODNs, alone or subsequent to
      treatment with a single injection of cyclophosphamide, to suppress the leukemic
      process induced in severe combined immunodeficient (SCID) mice by Philadelphia
      cells (i.e., primary CML-blast crisis [CML-BC] cells). In addition, we studied
      potential mechanisms that might explain the efficacy of the bcr/abl antisense
      [S]ODN-mafosfamide combination against Philadelphia cells in vitro. METHODS: The
      effects of treating leukemic mice with cyclophosphamide (25 mg/kg body weight;
      25% of the dose required to eradicate evidence of leukemia in SCID mice) and/or
      bcr/abl antisense [S]ODNs were assessed by analysis of survival, by examination
      of bone marrow for the presence of leukemia cells (using a colony formation assay
      or using coupled reverse transcription and the polymerase chain reaction to
      screen for bcr/abl messenger RNA), and by examination of a variety of tissues for
      the presence of infiltrating leukemia cells. The induction of apoptosis (a cell
      death program) in vitro in primary CML-BC cells following treatment with bcr/abl
      antisense [S]ODNs plus or minus prior treatment with mafosfamide was monitored by
      use of a commercial assay. Relative cellular uptake of [S]ODNs by CML-BC cells
      treated in vitro with or without prior treatment with mafosfamide was determined
      by use of confocal microscopy and flow cytometry (for fluorescent [S]ODNs) or by
      use of blotting techniques that employed radioactively labeled probes (for
      extracted, unlabeled [S]ODNs). Levels of specific proteins in treated and
      untreated cells were determined by use of western blotting methods. Reported P
      values are two-sided. RESULTS: The disease process in leukemic mice was retarded
      substantially by combination treatment with cyclophosphamide and specific bcr/abl
      antisense [S]ODNs (P < .001, relative to treatment with specific antisense
      [S]ODNs alone, cyclophosphamide alone, or cyclophosphamide plus nonspecific
      [i.e., control] antisense [S]ODNs); 50% of the mice treated with cyclophosphamide
      and specific antisense [S]ODNs appeared to be cured of leukemia. The combination
      treatment was associated with increased induction of apoptosis. In addition,
      cellular uptake of bcr/abl antisense [S]ODNs appeared to be increased twofold to
      sixfold by prior treatment with mafosfamide. This increased uptake of [S]ODNs was
      associated with enhanced suppression of p210bcr/abl protein levels. CONCLUSIONS
      AND IMPLICATIONS: Combination therapy with antisense [S]ODNs targeted to specific
      oncogenes and less toxic doses of anticancer drugs may represent a rational
      strategy to purpose for the treatment of human leukemias.

PMID- 8998182
TI  - Prostate-specific antigen (PSA) and PSA density: racial differences in men
      without prostate cancer.
AB  - BACKGROUND: Many physicians now use serum prostate-specific antigen (PSA) to
      screen for prostate cancer in asymptomatic men. Whether or not a prostate biopsy
      should also be performed depends on an accurate definition of what constitutes a
      normal PSA value. Until recently, studies conducted to establish normal serum PSA
      values have involved study populations that have included few African-American
      men. PURPOSE: We sought to compare serum PSA levels and PSA density (i.e., serum
      PSA level/prostate volume ratio) in African-American and white men without
      histologic evidence of prostate cancer. METHODS: We reviewed the medical records
      of 826 consecutive men who underwent one or more prostate biopsies at the
      Veterans Affairs Medical Center in Shreveport, LA, from January 1993 through
      December 1995. In this retrospective review, we recorded patient's age, race,
      serum PSA level, digital rectal examination result, ultrasound-determined
      prostate volume, indications for biopsy, and biopsy results. Data from a total of
      752 consecutive men who were either white or African-American and whose
      indication for biopsy included a serum PSA of greater than 4.0 ng/mL and/or an
      abnormal digital rectal examination were analyzed. To examine possible
      differences in serum PSA level, PSA density, prostate volume, and patient age,
      the two-sided Student's t test was employed. Multivariate linear regression
      analysis was used to determine if serum PSA levels were associated with the
      patient's age, race, or prostate volume in men without prostate cancer. RESULTS:
      Of the 752 men included in this analysis, 254 had histologic evidence of prostate
      cancer and 498 did not. Of the 498 men without prostate cancer, 367 (74%) men
      were white and 131 (26%) were black. There were no racial differences in age or
      calculated prostate volume. Serum PSA levels and calculated PSA density, however,
      were significantly (both P < .0001) higher in African-American men that in white
      men. A multivariate linear regression analysis indicated that race and prostate
      volume were independent variables associated with serum PSA level. For African
      American and white men, serum PSA values of greater than 4 ng/mL were associated
      with prostate cancer with sensitivities of 89.5% and 81.9%, respectively, and
      specificities of 38.2% and 52.3%, respectively. CONCLUSION: Among biopsied men
      without histologic evidence of prostate cancer, African-Americans have a
      significantly higher PSA level and PSA density than similarly aged white men.
      IMPLICATIONS: Published criteria for normal PSA level and density have been
      derived primarily from white men and may not be directly applicable to other
      populations. Race-specific data are needed to fully optimize PSA as a tumor
      marker in racial populations that are at high risk for prostate cancer death.

PMID- 8998183
TI  - Prognostic significance of vascular endothelial growth factor protein in node
      negative breast carcinoma.
AB  - BACKGROUND: The clinical outcome is generally positive for patients with node
      negative breast carcinoma (i.e., those who do not have detectable metastases in
      the lymph nodes) who have been treated with surgery or surgery plus radiation
      therapy. In about 30% of the patients, however, the disease recurs, and they are
      at risk of death. Determination of valid new prognostic indicators would improve
      the ability to identify patients at high risk of recurrence. Breast cancer can
      entail substantial development of new blood vessels within the tumor tissue, and
      it is known that the growth and metastasis of solid tumors are dependent on such
      angiogenesis. The conversion of tumor cells to an angiogenic phenotype may be
      preceded by a change in the balance of angiogenic growth factors and angiogenesis
      inhibitors. PURPOSE: This study was conducted to determine if the levels of
      vascular endothelial growth factor (VEGF) protein, a potent endothelial growth
      factor and mediator of vascular permeability and angiogenesis, measured in the
      primary tumors of women with node-negative breast cancer are associated with
      known prognostic factors and patient survival. METHODS: By use of a selective
      enzymatic immunoassay, levels of VEGF protein were measured in cytosolic extracts
      of primary tumor tissue surgically obtained from 260 women with node-negative
      breast carcinoma who had been treated with surgery with or without radiation
      therapy but not with adjuvant therapy and who had been followed for a median time
      of 66 months. The relationships between VEGF concentrations and other prognostic
      dichotomous variables or clinical outcome were tested by the use of the
      Kolmogorov-Smirnov test and univariate and multivariate Cox analyses,
      respectively. The relationship between VEGF and hormone receptors (i.e., those
      for estrogen and progesterone) was examined by the use of Spearman's correlation
      analyses. All P values resulted from the use of two-sided statistical tests.
      RESULTS: Tumors from 247 (95%) of the 260 patients had detectable VEGF, ranging
      in concentration from 5.0 to 6523 pg/mg protein (median, 126.25 pg/mg protein).
      No statistically significant associations were found between VEGF and the other
      prognostic factors (e.g., age, menopausal status, histologic tumor type, tumor
      size, and hormone receptors) examined. Levels of VEGF were found to be prognostic
      for both relapse-free and overall survival in univariate and multivariate
      analyses (likelihood ratio tests; all four P values < .001). In the multivariate
      analysis, the first-order interaction term of VEGF and estrogen receptor was also
      prognostic for overall survival (likelihood ratio test; P = .05). CONCLUSIONS:
      The results show that cytosolic levels of VEGF in tumor tissue samples are
      indicative of prognosis for patients with node-negative breast carcinoma.

PMID- 8998184
TI  - Controlled trial of pretest education approaches to enhance informed decision
      making for BRCA1 gene testing.
AB  - BACKGROUND: In response to the isolation of the BRCA1 gene, a breast-ovarian
      cancer-susceptibility gene, biotechnology companies are already marketing genetic
      tests to health care providers and to the public. Initial studies indicate
      interest in BRCA1 testing in the general public and in populations at high risk.
      However, the optimal strategies for educating and counseling individuals have yet
      to be determined. PURPOSE: Our goal was to evaluate the impact of alternate
      strategies for pretest education and counseling on decision-making regarding
      BRCA1 testing among women at low to moderate risk who have a family history of
      breast and/or ovarian cancer. METHODS: A randomized trial design was used to
      evaluate the effects of education only (educational approach) and education plus
      counseling (counseling approach), as compared with a waiting-list (control)
      condition (n = 400 for all groups combined). The educational approach reviewed
      information about personal risk factors, inheritance of cancer susceptibility,
      the benefits, limitations, and risks of BRCA1 testing, and cancer screening and
      prevention options. The counseling approach included this information, as well as
      a personalized discussion of experiences with cancer in the family and the
      potential psychological and social impact of testing. Data on knowledge of
      inherited cancer and BRCA1 test characteristics, perceived risk, perceived
      benefits, limitations and risks of BRCA1 testing, and testing intentions were
      collected by use of structured telephone interviews at baseline and at 1-month
      follow-up. Provision of a blood sample for future testing served as a proxy
      measure of intention to be tested (in the education and counseling arms of the
      study). The effects of intervention group on study outcomes were evaluated by use
      of hierarchical linear regression modeling and logistic regression modeling (for
      the blood sample outcome). All P values are for two-sided tests. RESULTS: The
      educational and counseling approaches both led to significant increases in
      knowledge, relative to the control condition (P < .001 for both). The counseling
      approach, but not the educational approach, was superior to the control condition
      in producing significant increases in perceived limitations and risks of BRCA1
      testing (P < .01) and decreases in perceived benefits (P < .05). However, neither
      approach produced changes in intentions to have BRCA1 testing. Prior to and
      following both education only and education plus counseling, approximately one
      half of the participants stated that they intended to be tested; after the
      session, 52% provided a blood sample. CONCLUSIONS: Standard educational
      approaches may be equally effective as expanded counseling approaches in
      enhancing knowledge. Since knowledge is a key aspect of medical decision-making,
      standard education may be adequate in situations where genetic testing must be
      streamlined. On the other hand, it has been argued that optimal decision-making
      requires not only knowledge, but also a reasoned evaluation of the positive and
      negative consequences of alternate decisions. Although the counseling approach is
      more likely to achieve this goal, it may not diminish interest in testing, even
      among women at low to moderate risk. Future research should focus on the merits
      of these alternate approaches for subgroups of individuals with different
      backgrounds who are being counseled in the variety of settings where BRCA1
      testing is likely to be offered.

PMID- 8998186
TI  - Association of prostate cancer risk with genetic polymorphisms in vitamin D
      receptor and androgen receptor.
AB  - BACKGROUND: Prostate cancer is an increasingly common disease for which there are
      few well-established risk factors. Family history data suggest a genetic
      component; however, the majority of prostate cancer cases cannot be explained by
      a single-gene model. Prostate cell division is influenced by two steroid
      hormones, testosterone and vitamin D, the action of each being mediated by its
      respective receptor. The genes for the two receptors are candidates in a
      multigenic model for prostate cancer susceptibility. PURPOSE: We examined genetic
      polymorphisms in two steroid receptors, the androgen receptor (AR) and the
      vitamin D receptor (VDR), in a case-control pilot study of prostate cancer.
      METHODS: Fifty-seven non-Hispanic white case patients with prostate cancer and
      169 non-Hispanic white control subjects were genotyped for a previously described
      microsatellite (CAG repeats) in the AR gene and for a newly discovered poly-A
      microsatellite in the 3'-untranslated region (3'UTR) of the VDR gene. To compare
      genotypes with respect to prostate cancer risk, we estimated odds ratios (ORs) by
      using logistic regression. ORs were also estimated separately for advanced and
      localized cases of disease. All P values resulted from two-sided tests. RESULTS:
      Both the AR and the VDR polymorphisms were associated, individually and after
      mutual adjustment, with prostate cancer. Adjusted ORs (95% confidence intervals
      [CIs]) for prostate cancer were 2.10 (95% CI = 1.11-3.99) for individuals
      carrying an AR CAG allele with fewer than 20 repeats versus an allele with 20 or
      more repeats and 4.61 (95% CI = 1.34-15.82) for individuals carrying at least one
      long (A18 to A22) VDR poly-A allele versus two short (A14 to A17) poly-A alleles.
      For both the AR and VDR genes, the at-risk genotypes were more strongly
      associated with advanced disease than with localized disease. CONCLUSIONS: In
      this pilot study, genetic variation in both the VDR and the AR genes was
      associated with prostate cancer, and both genes appear to preferentially confer
      risk for advanced disease. These two genetic risk factors, if confirmed, are
      among the strongest risk factors yet identified for prostate cancer.
      IMPLICATIONS: These results are consistent with a multigenic model of prostate
      cancer susceptibility. On the basis of the joint effect of several genetic loci,
      one might ultimately be able to construct a risk profile to predict advanced
      disease, so that men whose disease is unlikely to progress to an advanced stage
      can possibly be spared aggressive treatment.

PMID- 8998185
TI  - p53 status and prognosis of locally advanced prostatic adenocarcinoma: a study
      based on RTOG 8610.
AB  - BACKGROUND: The p53 tumor suppressor gene (also known as TP53) is one of the most
      frequently mutated genes in human cancer. Several studies have shown that p53
      mutations are infrequent in prostate cancer and are associated with advanced
      disease. PURPOSE: We assessed the prognostic value of identifying abnormal p53
      protein expression in the tumors of patients with locally advanced prostate
      cancer who were treated with either external-beam radiation therapy alone or
      total androgen blockade before and during the radiation therapy. METHODS: The
      study population consisted of a subset of patients entered in Radiation Therapy
      Oncology Group protocol 8610 ("a phase III trial of Zoladex and flutamide used as
      cytoreductive agents in locally advanced carcinoma of the prostate treated with
      definitive radiotherapy"). Immunohistochemical detection of abnormal p53 protein
      in pretreatment specimens (i.e., needle biopsies or transurethral resections) was
      achieved by use of the monoclonal anti-p53 antibody DO7; specimens in which 20%
      or more of the tumor cell nuclei showed positive immunoreactivity were considered
      to have abnormal p53 protein expression. Associations between p53 protein
      expression status and the time to local progression, the incidence of distant
      metastases, progression-free survival, and overall survival were evaluated in
      univariate (logrank test) and multivariate (Cox proportional hazards model)
      analyses. Reported P values are two-sided. RESULTS: One hundred twenty-nine (27%)
      of the 471 patients entered in the trial had sufficient tumor material for
      analysis. Abnormal p53 protein expression was detected in the tumors of 23 (18%)
      of these 129 patients. Statistically significant associations were found between
      the presence of abnormal p53 protein expression and increased incidence of
      distant metastases (P = .04), decreased progression-free survival (P = .03), and
      decreased overall survival (P = .02); no association was found between abnormal
      p53 protein expression and the time to local progression (P = .58). These results
      were independent of the Gleason score and clinical stage. A significant treatment
      interaction was detected with respect to the development of distant metastases:
      Among patients receiving both radiation therapy and hormone therapy, those with
      tumors exhibiting abnormal p53 protein expression experienced a reduced time to
      the development of distant metastases (P = .001); for patients treated with
      radiation therapy alone, the time to distant metastases was unrelated to p53
      protein expression status (P = .91). CONCLUSIONS: Determination of p53 protein
      expression status yield significant, independent prognostic information
      concerning the development of distant metastases, progression-free survival, and
      overall survival for patients with locally advanced prostate cancer who are
      treated primarily with radiation therapy. IMPLICATIONS: The interaction of
      radiation therapy plus hormone therapy and abnormal p53 protein expression may
      provide a clinical link to experimental evidence that radiation therapy and/or
      hormone therapy act, at least in part, by the induction of apoptosis (a cell
      death program) and suggests that this mechanism may be blocked in patients whose
      tumors have p53 mutations.

PMID- 8998187
TI  - Serum troponin T levels in adults undergoing anthracycline therapy.

PMID- 8998188
TI  - Re: Healthy People 2000 review: women's cancers.

PMID- 8998189
TI  - Re: Response of aleukemic granulocytic sarcoma to all-trans-retinoic acid plus
      interferon alfa-2a.

PMID- 8998190
TI  - A rare case of prednimustine-induced myoclonus.

PMID- 8998191
TI  - Circulating prostate-specific antigen/CD14-double-positive cells: a biomarker
      indicating low risk for hematogeneous metastasis of prostate cancer.

PMID- 8998192
TI  - Vascular smooth muscle cell phenotype influences glycosaminoglycan composition
      and growth effects of extracellular matrix.
AB  - Rat neonatal and neointimal vascular smooth muscle cells differ dramatically from
      adult medical vascular smooth muscle cells in their growth properties, with the
      neonatal and neointimal cells exhibiting growth in the absence of exogenously
      added growth factors. Since it has been hypothesized that extra-cellular matrix
      proteoglycans may influence the growth and differentiation of vascular smooth
      muscle cells, we examined the ability of matrix derived from these cells to
      influence vascular smooth muscle cell proliferation. To produce test matrices,
      cells were grown to confluence and removed by brief alkali treatment. Test cells
      were seeded onto these matrices and the rates of growth in a growth-factor
      deficient medium determined. Compared to plastic wells, matrix from neonatal or
      neointimal cells stimulated the growth of vascular smooth muscle cells.
      Interestingly, matrix from adult cells was less efficient at promoting growth.
      Enzymatic digestion of extracellular matrix heparan sulfate, but not of other
      glycosaminoglycans, further increased the growth-stimulatory effect of
      extracellular matrix, suggesting that matrix heparan sulfate acts as a growth
      inhibitor. Consistent with this, biochemical analysis showed that the adult
      matrix contained a higher percentage of heparan sulfate compared with neonatal or
      neointimal matrix. These results suggest that autocrine production of heparan
      sulfate proteoglycans may play an important role in growth regulation of vascular
      smooth muscle cells during normal vascular development and differentiation as
      well as in pathological response to injury.

PMID- 8998193
TI  - Atherosclerosis resistance in rats correlates with lack of expansion of an
      immature smooth muscle cell population.
AB  - In this study we asked whether the well-known atherosclerosis resistance of rats
      might be reduced with aging. Two groups of young, adult and aged Wistar rats, one
      of which was kept on a standard, low-cholesterol (CT) diet, and the other one was
      fed a 2% CT diet for 2 months were enrolled. Potential modifications in the
      phenotypic profile of aortic smooth muscle (SM) were assessed by SDS-gel
      electrophoresis, Western blotting and immunofluorescence procedures using a panel
      of monoclonal antibodies to myosin isoforms, cytoskeletal and extracellular
      matrix proteins. With development and aging, the expression of 196-kD non-muscle
      type myosin heavy-chain isoform (MyHC), the EIIIA fibronectin variant and
      keratins was downregulated, whereas that of the 204- and 200-kD SM-type MyHC
      isoforms, SM-type alpha-actin and desmin did not change. The levels of
      hypercholesterolemia achieved in this model did not substantially modify the
      distribution of the downregulated markers, except for the subendothelial grouping
      of immature SM cells in aged rats. Morphometric measurements indicated a slight
      increase of medial cross-sectional area accompanied by a decrease in total SM
      cell number, both with aging and with hypercholesterolemia. In no circumstance
      was the presence of atherosclerotic lesions histologically detectable. Bromo
      deoxyuridine (BrdU) incorporation analysis revealed a marked age-dependent
      decline in DNA synthesis and the formation of binucleated cells in aged aortas.
      This pattern was not influenced by hypercholesterolemia, except in aged rats
      where BrdU-positive SM cells are almost doubled. Our data indicate that aging and
      hypercholesterolemia cannot affect the phenotypic stability of rat SM cells and
      confirm that the change from a fully differentiated to an immature state is a
      general prerequisite to allow the development of atherosclerotic lesions in
      mammalian species.

PMID- 8998194
TI  - Diminishment of contractions associated with depolarization-evoked activation of
      Ca2+ channels in diabetic rat aorta.
AB  - Alterations in contractile responses of aortic rings mediated by activation of
      Ca2+ channels were investigated in rats with streptozotocin-induced diabetes.
      Eight to 12 weeks of diabetes resulted in a marked decrease in the contractile
      response of aortic rings to high K+. In contrast, diabetic aortas exhibited
      significantly greater contractions in response to noradrenaline compared to age
      matched controls. In the presence of 15 mM K+, the Ca2+ channel agonist Bay K
      8644 consistently produced concentration-dependent contractions in control
      aortas. On the other hand, the half of diabetic aortas did not respond to Bay K
      8644. As a result, the contractile response to Bay K 8644 was significantly less
      in diabetic aortas compared to controls. There was no significant difference in
      basal 45Ca2+ uptake between control and diabetic aortas. However, the uptake of
      45Ca2+ induced by high K+ was significantly less in diabetic aortas than in
      controls, and pretreatment with the Ca2+ channel antagonist nifedipine abolished
      both responses. The resting membrane potentials were not significantly different
      between control and diabetic aortas. Furthermore, no difference was found in the
      magnitude of depolarization evoked by increasing K+ concentrations between the
      two groups of tissues. There were no significant differences in the density and
      the dissociation constant for [3H]-(+)-PN200-110, a radiolabeled Ca2+ channel
      antagonist, between aortic membranes from control and diabetic rats. These data
      indicate that the contractile responses to high K+ and Bay K 8644 are
      specifically diminished in diabetic aortas. These diminished responses are not
      due to a difference in the number of Ca2+ channels, but may be related to an
      alteration in activation of the channels by membrane depolarization.

PMID- 8998195
TI  - Impairment of acetylcholine relaxations by malondialdehyde, a marker of lipid
      peroxidation.
AB  - The effect of malondialdehyde (MDA), a lipid peroxidation marker, on the
      relaxations evoked by acetylcholine (ACh) was analyzed in tail arteries of
      Sprague-Dawley rats, which have MDA plasma levels of 0.43 +/- 0.10 microM. MDA
      (0.5-30 microM) produced an inhibition of ACh relaxations that persisted after
      repeated washing periods, and was independent of the incubation time. MDA did not
      modify the vasodilator responses to either exogenous nitric oxide (NO) or sodium
      nitroprusside, a NO donor. L-Arginine (the NO synthase substrate) did not prevent
      the impairment of relaxations to ACh caused by MDA. The association of N omega
      nitro-L-arginine methyl ester (a NO synthase inhibitor) and MDA produced an
      additive inhibition of the ACh-induced relaxations. Superoxide dismutase (a
      superoxide anion scavenger) completely reversed the inhibitory effect of MDA.
      These results suggest: (1) MDA is not only a marker of lipid peroxidation but
      also an agent that can impair endothelium-dependent relaxations; (2) this
      impairment does not seem to be due to an interference with guanylate cyclase
      activation by NO or with NO synthase pathway; (3) the effect of MDA appears to be
      mediated by superoxide anion, and (4) MDA could propagate lipid peroxidation
      chain reactions in endothelial membranes, that could alter the function of
      muscarinic receptors.

PMID- 8998196
TI  - Nitric oxide maintains dilation of immature and mature collaterals in rat
      hindlimb.
AB  - The role of nitric oxide (NO) in maintaining collateral dilation was investigated
      in rats with acute and chronic superficial femoral artery occlusion. Collateral
      function was evaluated from arterial pressure measurements proximal (mean
      arterial pressure, MAP) and distal (PD) to the occlusion under resting and
      hyperemic conditions. For resting and hyperemic conditions, respectively, PD
      increased with the duration of occlusion from 34 +/- 2.1 and 14 +/- 0.8 mm Hg
      acutely postocclusion to 37 +/- 2.8 and 19 +/- 3.6, 42 +/- 4.9 and 25 +/- 1.5,
      and 49 +/- 5.6 and 25 +/- 2.1 mm Hg at 1, 4, and 12 weeks. After NO synthase
      inhibition with N omega-nitro-L-arginine methyl ester (L-NAME), PD in control
      limbs increased but in occluded limbs decreased by 20 +/- 2.0 mm Hg (acute) and
      18 +/- 2.1, 15 +/- 4.4, and 20 +/- 8.1 mm Hg at 1, 4, and 12 weeks postligation,
      respectively. The percent of MAP (%MAP) dissipated by large arteries and
      collateral vessels decreased during collateral development (from 71 +/- 1.7%
      acutely to 57 +/- 2.2% at 12 weeks postligation) and was increased approximately
      20% by L-NAME at each time point. The rise in PD and decrease in %MAP dissipated
      by collaterals following chronic occlusion indicates that significant collateral
      development occurred. The fall in PD and increase in %MAP dissipation after L
      NAME administration suggest that NO-mediated vasodilatory tone is maintained
      throughout the period of collateral development.

PMID- 8998197
TI  - The role of angiotensin II and prostaglandins in arcade formation in a developing
      microvascular network.
AB  - There are basically two types of branching patterns in the terminal part of the
      arteriolar tree. On the one hand, in a number of tissues, including the
      developing chick embryo chorioallantoic membrane (CAM), the pattern is
      dichotomous, whereas in other tissues many arteriolar-arteriolar connections,
      arcades, are found. The structure of the branching pattern depends on the local
      physical and chemical environment. The goal of this study was to investigate
      whether substances with an effect on vascular growth influence the vascular
      branching pattern. We treated chick embryo CAMs daily from day 7 to day 14
      postfertilization with 0.9% NaCl, angiotensin II (ANG-II), ANG-II in combination
      with different angiotensin receptor subtype antagonists, i.e., losartan and CGP
      42112A, or the prostaglandin synthesis inhibitor acetylsalicylic acid (ASA).
      Arcade formation was quantified by counting the number of arcades per cm2 treated
      area, the branch-node ratio and mean surface area of arcade loops. ANG-II caused
      a 2-fold increase in the number of arcades versus 0.9% NaCl. Addition of ASA or
      losartan caused a further enhancement of arcade formation expressed in the number
      and branch-node ratio. CGP 42112A had no significant effect on arcade formation.
      From these data we hypothesize that ANG-II stimulates the process of capillary
      upgrading to arterioles by stimulation of arteriolar smooth muscle cell growth.
      Prostaglandins normally counteract this effect. After blockade of prostaglandin
      action, the ANG-II-induced arterialization is enhanced, resulting in pronounced
      arcade formation. The actions of losartan may be related to its inhibitory
      effects on prostaglandins rather than angiotensin receptor antagonism.

PMID- 8998198
TI  - Memory of previous receptor activation induces a delay in Ca2+ mobilization and
      decreases the [Ca2+]i sensitivity of arterial contractions.
AB  - alpha 1-Adrenoceptor agonists not only contract rabbit femoral arteries, but also
      desensitize them so that the strength of subsequent contractions induced by 110
      mM KCl is reduced. To determine the mechanisms by which this postreceptor
      desensitization occurs, tissues loaded with fura-2/AM were pretreated with
      phenylephrine (PE), washed, then activated with submaximum (23 mM) and maximum
      (30 mM) KCl concentrations. Pretreatment of tissues with 1 microM PE for 1-30 min
      resulted in reductions compared to control in the ability of 30 mM KCl to
      increase stress (force/tissue cross-sectional area). Pretreatment durations of 20
      or 30 min with 10 microM PE also introduced delays between addition of KCl and
      commencement of both contraction (9.8 +/- 0.8 and 2.4 +/- 1.4 min when stimulated
      with, respectively, 23 and 30 mM KCl) and an increase in [Ca2+]i. At the end of
      the delay period, both [Ca2+]i and stress spontaneously increased, but although
      [Ca2+]i increased to control levels, stress did not. These data support the
      hypothesis that at least two postreceptor desensitizing mechanisms are activated
      by prior alpha 1-adrenoceptor stimulation: (1) short-term inhibition of stimulus
      induced increases in [Ca2+]i and (2) reductions in the sensitivity of the
      contractile response to [Ca2+]i. Interestingly, caffeine pretreatment mimicked
      the actions of PE pretreatment, implying that the superficial buffer barrier
      function of the sarcoplasmic reticulum or increases in cyclic nucleotide levels
      may have played a role in memory of alpha-adrenoceptor activation in rabbit
      femoral arteries.

PMID- 8998199
TI  - Understanding changes in health status. Is the floor phenomenon merely the last
      step of the staircase?
AB  - OBJECTIVES: Previous studies have found that health-status measures may be unable
      to detect clinically important changes for patients whose baseline health is poor
      (the "floor phenomenon"). It is not known whether this inability to detect change
      is confined to patients in very poor baseline health or whether the sensitivity
      of health-status instruments varies across the entire range of health states. The
      goals of this study were to see how changes in physical health, mental health,
      and overall health (1) depend on baseline (usual) health and (2) compare with
      patients' global assessment of changes in their health. METHODS: Stable,
      ambulatory patients presenting to the emergency department of a public hospital
      retrospectively rated their usual physical health (eight items), mental health
      (three items), and overall health (one item); their health on the day of study
      entry using these same items; and their global assessment of the change in their
      health compared with baseline. Complete information on these items was available
      for 1,005 patients. Baseline scores on the physical and mental health subscales
      and the overall health item were divided into five categories: 81 to 100 (best),
      61 to 80, 41 to 60, 21 to 40, and 0 to 20 (worst). RESULTS: The mean difference
      in health from baseline to emergency department presentation decreased as the
      baseline health category worsened, as follows: physical health, -26.0, -35.9, 
      15.1, -9.5, +1.0; mental health, -23.0, -16.1, -9.6, 0.0, 6.6; overall health 
      64.0, -45.3, -28.4, -8.4, 10.4, respectively. However, patients' global
      assessment of health change showed the opposite trend; the proportion of patients
      rating their health as "much worse" than baseline increased as baseline health
      worsened. When only patients whose physical health score declined less than 10
      points were analyzed, 14% of those in the best baseline health said their health
      was "much worse," whereas 74% of those with the worst baseline physical health
      said their health was "much worse" than baseline. CONCLUSIONS: These findings
      suggest that the sensitivity of health-status measures to change and the meaning
      of an incremental change in physical health or mental health vary depending on
      baseline health. This may result from noninterval properties of response options
      or from patients being at the lowest health state (the "floor") of individual
      questions. If health-status measures similar to this are to be used to compare
      the outcomes of treatment across diseases and for patients in a wide variety of
      baseline health states, weighting schemes may be needed to account for these
      effects.

PMID- 8998200
TI  - Practice variation and the risk of low birth weight in a public prenatal care
      program.
AB  - OBJECTIVES: Use of antepartum tests of fetal well-being is widespread even though
      effectiveness in preventing fetal damage or stillbirth has not been established.
      The study objective was to examine whether aggressive use of these tests might
      contribute to increased rates of other birth outcomes, including low birth weight
      (LBW). METHODS: A total of 3,235 low-income women receiving care from 28 clinic
      sites were studied. All women were eligible for Medi-Cal benefits. Clinic sites
      were classified as aggressive, moderate, or low users of antepartum tests. The
      relations between patient risk factors, clinic testing style, LBW, and other
      pregnancy outcomes were examined using multiple logistic regression. RESULTS:
      After adjustment for risk factors, patients seen by aggressive testers had a risk
      of LBW higher than patients receiving care from moderate testers (odds ratio =
      1.65; P < 0.01). Rates of LBW within patients receiving care from moderate and
      low testers did not differ (P = 0.22). Patients seen by aggressive testers also
      had higher rates of preterm delivery, cesarean delivery, and provided more
      expensive care. CONCLUSIONS: Although antepartum testing is intended to prevent
      fetal distress, extremely aggressive use of antepartum testing may have
      unfavorable effects on LBW and other pregnancy outcomes. More attention should be
      paid to variation in obstetric practices in evaluations of the costs and
      effectiveness of public prenatal care programs.

PMID- 8998201
TI  - Policy analysis of the conversion of histamine2 antagonists to over-the-counter
      use.
AB  - OBJECTIVES: The authors assess the costs associated with treatment of dyspepsia
      with histamine2 antagonists versus without availability of over-the-counter
      (OTC). METHODS: A cost analysis was performed using a decision-analysis model.
      Patients with an initial episode of dyspepsia were studied. The model includes
      costs associated with consumption of OTC and prescription (Rx) medications for
      dyspepsia, physician visits and associated diagnostic testing, time spent for
      physician visits and diagnostic tests, and hospitalization costs. RESULTS: The
      model is sensitive to the relative cost of histamine2 antagonists when purchased
      Rx or OTC, as well as to the efficacy of these drugs in relieving dyspeptic
      symptoms. For patients with nonulcer dyspepsia (the largest group of likely
      consumers), the model demonstrates a cost savings if the OTC cost of the
      medication is slightly less than one third the Rx cost. Costs are similar whether
      or not histamine2 antagonists are available OTC. If the symptom relief efficacies
      of histamine2 antagonists are equivalent whether purchased by prescription only
      or OTC, then the health-care expenditures for a typical patient with dyspepsia
      are $204 for OTC availability and $203 for Rx-only use. Viewing costs from the
      perspective of a managed-care organization, expenditures for an episode of
      dyspepsia are $149 regardless of whether or not histamine2 antagonists are
      available OTC. Restricting the analysis to patients with underlying nonulcer
      dyspepsia yields similar results. Variation of numerous assumptions and
      probabilities other than histamine antagonist cost and efficacy, including costs
      associated with physician visits and diagnostic tests, and the likelihood of
      seeking medical care, do not substantially affect the results of the model.
      CONCLUSIONS: Health-care costs associated with initial treatment of dyspepsia are
      similar regardless of the availability of histamine2 antagonists OTC. This is due
      largely to the similar efficacy of these drugs compared with antacids and the
      predicted increase in diagnostic testing that may result if a patient visits a
      physician after failure to achieve symptom relief with OTC use of histamine2
      antagonists.

PMID- 8998202
TI  - Assessment of coronary artery bypass graft surgery performance in New York. Is
      there a bias against taking high-risk patients?
AB  - OBJECTIVES: The purpose of this study was to determine whether performing
      coronary artery bypass surgery on high-risk patients adversely affects the risk
      adjusted mortality rates for patients of surgeons and hospitals in New York State
      compared with the impact of performing surgery on more routine patients. METHODS:
      Risk-adjusted mortality-rates were calculated for 31 hospitals and 87 surgeons
      for high-risk (a predicted mortality rate of at least 7.5%) and low-risk patients
      during the time period 1990 to 1992. RESULTS: The risk-adjusted mortality for all
      high-risk patients was lower (2.94%) than the risk-adjusted mortality for other
      patients (3.02%). Fifteen of the 31 hospitals had a lower risk-adjusted mortality
      for all patients than they did for low-risk patients only, and no differences in
      either direction were statistically significant. Forty-one of 87 surgeons (47%)
      had risk-adjusted mortality for all patients that was at least as low as the risk
      adjusted mortality for low-risk patients. In general, hospitals and surgeons with
      the lowest risk-adjusted mortality for all cases also had the lowest risk
      adjusted mortality for high-risk cases. CONCLUSIONS: The authors conclude that
      there is no systematic bias against operating on high-risk coronary artery bypass
      graft patients in the risk-adjusted performance system in New York.

PMID- 8998203
TI  - A method of comparison for standardized rates of low-incidence events.
AB  - The authors present an approximate but simple approach to comparing age-gender
      standardized rates of low-incidence events (mortality or morbidity) rates across
      several geographic areas. The presented method will be useful particularly when a
      person-level database, one that includes unique person identifiers, is not
      available. We specify conditions under which comparisons can be made without
      calculating empirical standard errors and worrying unduly about recurrent events.
      To compare indirectly standardized rates, only information on the size, the crude
      rate, and the standardized rate of the areas are needed. For comparing directly
      standardized rates, which requires stratum-specific rates, the method also
      requires stratum-specific total numbers of events and individuals but does not
      require person-level information. The proposed approach builds on previous work
      comparing rates using person-level data.

PMID- 8998204
TI  - Assessing inner-city patients' hospital experiences. A controlled trial of
      telephone interviews versus mailed surveys.
AB  - OBJECTIVES: Obtaining accurate and representative patient-centered data may be
      difficult among poor, inner-city patients because of changing addresses, variable
      access to telephones, and a higher prevalence of illiteracy than in the
      populations in which many survey instruments were developed and tested.
      Assumptions about the usefulness of mailed surveys versus telephone interviews
      may not hold for the urban poor. Therefore, identifying the most efficient mode
      of survey administration in this population becomes an important methodological
      question. METHODS: We conducted a randomized trial of patients discharged from
      the inpatient medicine service of an urban teaching hospital to compare telephone
      interview with mailed self-administration of a detailed instrument for measuring
      patients' experiences with hospital care. Our primary outcomes were response
      rate, missing data, and data collection costs. Patients were excluded if they
      were not discharged to home or were mentally or physically unable to complete
      mailed or telephone interviews. The research assistant contacted eligible
      patients while hospitalized, informed them of the postdischarge survey, and
      obtained current phone numbers and addresses. Patients then were randomized to
      receive a 116-item satisfaction survey via one of two survey methods: mail-first
      (mailed surveys with follow-up on nonrespondents by telephone) or telephone-first
      (telephone interviews with follow-up of nonrespondents by mail). RESULTS: Of the
      252 patients enrolled, 130 were randomized to the mail-first and 122 to the
      telephone-first method. Response rates were higher with the telephone-first (73%)
      compared with the mail-first method (50%; P < 0.0001). Surveys obtained by the
      telephone-first method had fewer missing data (0.7 +/- 2.39) for those items not
      involved in skip patterns compared with the mail-first method (7.1 +/- 12.3; P <
      0.001) and were 42% less expensive per completed survey ($26.32 versus $37.35; P
      < 0.0001). CONCLUSIONS: In this survey of patients served by an urban teaching
      hospital, a strategy of telephone interviews with mail follow-up proved less
      expensive and yielded a higher response rate with more complete data than using a
      method where mailed surveys were followed by back-up telephone interviews. In
      addition, we believe that the improved response rate for telephone interviews
      compared with those reported in the literature for similar populations is the
      result of informing inpatients of the survey and obtaining telephone numbers and
      addresses in the hospital.

PMID- 8998205
TI  - Dental service use among adults with human immunodeficiency virus infection.

PMID- 8998206
TI  - Direct-to-consumer prescription drug advertising.

PMID- 8998207
TI  - Dedicated extremity MR imaging. An emerging technology.
AB  - Dedicated extremity MR imaging represents a radical departure from conventional
      whole-body scanning. Extremity MR imaging offers such advantages as reduced cost,
      more convenient and inexpensive setting, greater patient comfort and safety, and
      high diagnostic power. This article examines some of the features of extremity MR
      imaging and how this technology is affecting musculoskeletal imaging in today's
      environment of cost containment and health care reform.

PMID- 8998208
TI  - MR imaging of the knee menisci.
AB  - MR imaging of the knee is highly accurate for the noninvasive diagnosis of
      meniscal tears and other meniscal pathology. Familiarity with the normal anatomy
      and common pitfalls reduces errant interpretations, but does not eliminate them
      entirely. The two MR imaging signs of a meniscal tear are abnormal intrameniscal
      signal on a short-TE image that unequivocally contacts the meniscal surface, and
      abnormal meniscal morphology in the absence of prior meniscal surgery. To help
      guide the treatment of meniscal injuries, which continues to evolve, the MR
      imaging report should thoroughly describe tears, and not simply indicate whether
      a meniscal tear is present. In the patient with an ACL tear, the accuracy of MR
      imaging examination for meniscal tears, especially lateral tears, diminishes but
      still surpasses that of physical examination. The MR imaging criteria for
      meniscal tears need to be modified in patients who have undergone meniscal
      surgery.

PMID- 8998209
TI  - MR imaging of the knee ligaments and the postoperative knee.
AB  - MR imaging is an accurate, noninvasive, and cost-effective method for the
      evaluation of acute knee ligament injuries and in the examination of the
      postoperative knee. Understanding the normal anatomy and the pertinent clinical
      aspects of knee injuries is a prerequisite for accurate interpretation of MR
      imaging studies. The increasing popularity of ACL reconstruction following
      disruption of this ligament requires knowledge of the various surgical techniques
      and their MR imaging appearance as well as the appearance of possible
      complications.

PMID- 8998210
TI  - MR imaging of shoulder impingement and rotator cuff disease.
AB  - A number of imaging modalities, such as conventional radiography, arthrography,
      ultrasonography, and MR imaging, can be used in the evaluation of shoulder pain
      related to impingement, tendinosis, and rotator cuff tear. Of these techniques,
      only MR imaging provides anatomic information coupled with superior soft-tissue
      contrast. MR imaging of the shoulder effectively demonstrates a variety of
      morphologic abnormalities that may be associated with tendon degeneration.
      Rotator cuff tears are also well depicted and may be further characterized with
      regard to tendon involvement, degree of retraction, and secondary muscular
      atrophy.

PMID- 8998211
TI  - MR arthrography of the glenohumeral joint.
AB  - This article explores MR arthrography of the glenohumeral joint, including normal
      anatomy of the glenoid labrum, glenohumeral ligaments, and biceps labral complex.
      Examples of glenohumeral joint instability include the Bankart lesion, anterior
      labroligamentous periosteal sleeve avulsion, glenolabral articular disruption,
      humeral avulsion of the glenohumeral ligament, and Bennet lesion. Normal
      variations include the sublabral foramen, the Buford complex, and cord-like
      middle glenohumeral ligament. Labral tears and paralabral cysts are also
      discussed.

PMID- 8998212
TI  - MR imaging of the elbow. An update.
AB  - MR imaging provides clinically useful information in assessing the elbow joint.
      Superior depiction of muscles, ligaments, and tendons as well as the ability to
      visualize nerves, bone marrow, and hyaline cartilage directly are advantages of
      MR imaging relative to conventional imaging techniques. These features of MR
      imaging may help to establish the cause of elbow pain by accurately depicting the
      presence and extent of bone and soft-tissue pathology. Ongoing improvements in
      surface coil design and newer pulse sequences have resulted in higher quality MR
      images of the elbow that can be obtained more rapidly. Recent clinical experience
      has shown the utility of MR imaging in detecting and characterizing disorders of
      the elbow in a noninvasive fashion.

PMID- 8998213
TI  - MR imaging of the wrist.
AB  - The use of MR imaging in the area of the wrist has lagged due to the technical
      challenges posed by the small size of the structures of the wrist. After a
      careful history, physical examination, and plain films, MR imaging is a powerful
      next imaging study for solving diagnostic problems involving this complex region.
      The increasing ability of MR imaging to diagnose wrist abnormalities
      noninvasively has led to a decrease in the use of invasive techniques.

PMID- 8998214
TI  - MR imaging of the ankle and foot.
AB  - Optimal MR imaging of the ankle and foot demands attention to coil selection,
      patient positioning, and prescription of the imaging parameters. Though useful in
      the evaluation of many osseous conditions, MR imaging is perhaps most frequently
      used in the evaluation of osteochondral lesions and suspected osteomyelitis. Soft
      tissue masses with a predilection for the foot and ankle include plantar
      fibromatosis, ganglion cysts, and interdigital neuromas.

PMID- 8998215
TI  - MR imaging of bone marrow disorders.
AB  - This article discusses the MR imaging findings in osteomyelitis and septic
      arthritis. Criteria for differentiation of osteomyelitis from diabetic
      neuroarthropathy are presented. The article also presents an overview of MR
      imaging of avascular necrosis and criteria to differentiate transient
      osteoporosis from the edema pattern of avascular necrosis.

PMID- 8998216
TI  - Primary tumors of the musculoskeletal system.
AB  - The excellent soft-tissue contrast and multiplanar imaging capabilities of MR
      imaging have led to its emergence as the most significant advance in the imaging
      of musculoskeletal tumors. MR imaging is the modality of choice for local
      staging, evaluating response to preoperative chemotherapy, and long-term follow
      up in bone tumors. MR imaging is the most effective modality for both primary
      staging of soft-tissue malignancy and detecting recurrences. This article reviews
      the role of conventional spin echo techniques versus newer techniques, and then
      discusses the indications in the diagnosis, staging, evaluation of preoperative
      chemotherapy, and detection of recurrences in bone and soft-tissue tumors.

PMID- 8998217
TI  - The story of MEDUNSA.

PMID- 8998218
TI  - Taking research forward at MEDUNSA. Priority-setting, research infrastructure and
      capacity development.

PMID- 8998219
TI  - Curriculum development for the rural specialist.

PMID- 8998220
TI  - The British National Health Service.

PMID- 8998221
TI  - The Cardiothoracic Outreach Programme--a pilot project.
AB  - OBJECTIVE: To test the practicality, safety and benefits of major cardiothoracic
      surgery in two rural hospitals. DESIGN: Analysis of morbidity and mortality
      outcomes of a random collection of 35 patients, who underwent diverse surgical
      procedures. At each visit, the cardiothoracic team of Ga-Rankuwa Hospital-one
      surgeon, three registrars, two medical officers, six nurses, and four
      perfusionists-moved all equipment for major surgery, including bypass machines,
      to two small rural hospitals. Ga-Rankuwa Hospital, as a tertiary hospital
      attached to a medical school (Medical University of Southern Africa), mounted an
      outreach programme on a trial basis. The exercise was designed to render
      assistance, offer decentralised services, and test the skills of the
      cardiothoracic team in an environment where high-technology procedures have never
      been undertaken by the local health professionals. SETTING: Two rural hospitals,
      viz. Tintswalo and Mankweng, in the referral area of MEDUNSA, with no
      conventional ICU facilities. The support services for operative, pre-operative
      and postoperative care were very basic. The local personnel consisted only of
      general nurses and medical officers. None had experience of high-technology or
      complex theatre work. PARTICIPANTS: Thirty-five randomly selected patients of
      both sexes with ages ranging from 11 years to 64 years. Pre-operative diagnoses
      of diverse cardiac and lung conditions were made. The operations performed
      comprised 35 major procedures, including open heart operations and major lung
      procedures. The personnel comprised the MEDUNSA cardiothoracic team, who were
      assisted by local nurses. INTERVENTION AND OUTCOME: Thirty-five patients
      underwent 35 major procedures, all under general anaesthesia. Twenty
      cardiopulmonary bypasses were performed. There was 1 intra-operative death, due
      to low-output state. Intra-operative morbidity occurred in 2 of the 35
      operations. These consisted of a cerebrovascular accident (CVA) (air embolism),
      and a temporary heart block. Late outcomes (after 1 week) were also analysed; the
      incidence was 1/35 operations. This was a CVA due to a left atrial appendage
      clot. Staff morale at the local hospital improved remarkably. The process of
      teaching the local professional nurses was surprisingly easy. Benefits included a
      decreased referral rate (100%), lower costs (transport, medicines, operations),
      excellent patient and community confidence in the work of the hospitals
      (increased hospital outpatient numbers), and political support (new tools,
      upgraded facilities and new equipment). RESULTS: The exercise was a resounding
      success in both measurable and general terms. All operations were successfully
      performed, with very low adverse outcomes (morbidity, mortality) and good quality
      of life for all the subjects. The safety and cost-effectiveness of cardiothoracic
      surgery under primitive conditions were demonstrated. The standard of patient
      care improved, and local staff acquired good basic skills in patient care. The
      referral patterns changed for the better and the confidence of the community in
      the services was enhanced. The risk/benefit ratio of the exercise was
      commendable. The feasibility of an extended service was encouraging.

PMID- 8998222
TI  - Eclampsia at Ga-Rankuwa Hospital.
AB  - OBJECTIVES: To study the epidemiology of eclampsia and the maternal and fetal
      outcome of the disease. DESIGN: Observational study. SETTING: Ga-Rankuwa
      Hospital, a tertiary institution. SUBJECTS: Patients admitted with the diagnosis
      of eclampsia from 1 January 1994 to 31 December 1995. OUTCOME MEASURES: Age,
      parity, booking status, fits, blood pressure, gestational age, mode of delivery,
      fetal outcome, maternal complications and outcome. RESULTS: Out of 18145 women
      delivered, 66 had eclampsia (3.6/1000). Of the 36 maternal deaths in the same
      period, 14 (38.9%) were caused by eclampsia. The case fatality rate was 21.2%.
      Maternal mortality was significantly higher in the unbooked population, women
      aged 30 years and above, and those with multiple fits. The mean (SD) maternal age
      was 22.3 (6.8) years and fits occurred in the presence of high diastolic blood
      pressure (mean 113.7 +/- 15.6 mmHg). The majority of fits (90.1%) occurred at
      home and in 70.3% of patients, this happened before 37 weeks (mean gestational
      age 33.2 (3.9) weeks). In 77.3%, eclampsia was antepartum while it occurred
      postpartum in 4.5% of cases. The caesarean section rate of 66.7% is justified.
      The perinatal mortality rate was 47.7% and maternal complications were varied and
      severe. It is disturbing that health care providers failed to act on warning
      signs in 14 (46.7%) of the 30 booked patients that were evident long before they
      developed fits. CONCLUSION: Eclampsia is a problem and is responsible for a
      significant proportion of maternal deaths. The epidemiological factors
      responsible are identified and some recommendations are made. Patient and
      physician education, together with improved socio-economic conditions, are likely
      to improve the situation.

PMID- 8998223
TI  - The quality and relationship of referral and reply letters. The effect of
      introducing a pro forma letter.
AB  - OBJECTIVE: An intervention study was conducted to assess the effect of a pro
      forma letter on the quality of referral letters from general practitioners at a
      rural hospital in KwaZulu-Natal, and on the quality and rate of replies received.
      METHOD: 254 referral letters and 111 replies were evaluated. RESULTS: The quality
      of referral letters improved after the introduction of the pro forma letter, but
      the quality of replies did not. The reply rate (43.5%) did not change, and the
      quality of replies showed a low correlation with the quality of referral letters,
      indicating that improvements in the quality of referral letters will not
      necessarily bring about improvements in the quality of replies. Instead, the
      reply rate was found to be influenced mainly by the hospital to which the patient
      was referred. Replies were also observed to function poorly as a means of
      continuing medical education. CONCLUSION: Pro forma letters improve the quality
      of referral letters, but on their own do not improve the rate and quality of
      replies. Personal contact between referring doctors and consultants would seem to
      be an important factor in respect of the latter.

PMID- 8998225
TI  - Characterisation of rotaviruses recovered from neonates with symptomatic
      infection.
AB  - An unusually high number of diarrhoeal stools were obtained from neonates at
      different maternity units in Pretoria during late 1986 and the winter of 1987 and
      tested for the presence of rotavirus infection. Latex agglutination assay
      revealed rotavirus in 67% (93/139) of the stools from newborn babies. Gel
      electrophoresis of the rotavirus genome showed that a genomically stable strain
      of rotavirus was associated with the diarrhoeal illness in all maternity units
      investigated. Determination of the VP6 subgroup specificity using monoclonal
      antibodies demonstrated that all strains were of subgroup II. Examination of the
      VP4 and VP7 rotavirus genes, which encode for the outer capsid neutralisation
      proteins of the virus, was conducted by hybridisation analysis using probes
      directed at the divergent regions of the two genes. These results showed the
      presence of a VP7 serotype G4 rotavirus strain with a P6 VP4 genotype-the
      putative 'attenuated' VP4 gene allele-circulating in all maternity units studied.

PMID- 8998224
TI  - Molecular epidemiology of hepatitis C virus infection at Ga-Rankuwa Hospital.
AB  - Different hepatitis C virus (HCV) genotypes may be associated with viral load,
      severity of liver disease, hepatocellular carcinoma, geographical location and
      sensitivity to interferon. In this study the prevalence of HCV-RNA and
      distribution of HCV genotypes was investigated in anti-HCV-positive patients
      admitted to Ga-Rankuwa Hospital during 1994 and 1995. One hundred and forty-nine
      sera from three groups of anti-HCV-positive patients (N = 78) were analysed.
      These included: (i) patients with various liver diseases; (ii) patients admitted
      to the renal unit; and (iii) a miscellaneous group of patients for whom HCV
      antibody screening was requested. Twenty-six patients (33%) tested positive for
      viral RNA. Restriction fragment length polymorphism (RFLP) analysis of these
      patients showed that HCV genotypes 1, 2 and 5 were present. Type 2 (35%) was the
      dominant genotype in the region served by Ga-Rankuwa Hospital. In a large
      proportion of viral RNA-positive patients (27%), the polymerase chain reaction
      product could not be digested with one of the sets of enzymes, and therefore
      could not be classified into genotypes 1 to 6. Further studies are now in
      progress to enhance our current knowledge of the epidemiology of HCV infection.

PMID- 8998226
TI  - Atlanto-axial rotatory fixation.
AB  - OBJECTIVES: To analyse the causes of atlanto-axial rotatory fixation (AARF) and
      discuss the diagnosis and treatment. DESIGN: Retrospective case studies. SETTING:
      Medical University of Southern Africa-Ga-Rankuwa referral hospital. PATIENTS: A
      total of 10 patients admitted to and treated in the Department of Orthopaedics,
      Ga-Rankuwa Hospital, between July 1989 and June 1993. OUTCOME MEASURE: Dynamic
      computed tomography (CT) scan. RESULTS: Upper respiratory tract infection and
      trauma were the commonest causes of AARF. There was a delay in diagnosis ranging
      between 4 weeks and 2 years 6 months. Clinical and radiological reduction was
      obtained by gradual skeletal traction in 6 patients. Two patients had improvement
      of the torticollis but still had subluxation on the CT scan. In 1 patient no
      reduction was obtained on occipitocervical fusion and transoral decompression was
      necessary. In 1 case the parents refused any form of treatment. There was no
      recurrence in the 7 patients followed up (minimum 6 months). CONCLUSION: This
      study shows that AARF is often diagnosed late. The patients diagnosed early
      responded well to skeletal traction followed by external support. In patients
      diagnosed late the AARF could not be reduced completely and needed surgical
      fusion. If untreated, condition can be complicated by tetraparesis.

PMID- 8998227
TI  - There is life after the diagnosis.

PMID- 8998228
TI  - Intra-osseous lipoma of the calcaneus.

PMID- 8998229
TI  - Florid papillomatosis of the nipple ducts.

PMID- 8998230
TI  - Flying doctors, saving costs.

PMID- 8998231
TI  - Caesarean scar syndrome.

PMID- 8998232
TI  - Race as a research parameter.

PMID- 8998233
TI  - Therapeutic value of visual perceptual training.

PMID- 8998234
TI  - Herpes zoster--results from a questionnaire-based surveillance of patients and
      their general practitioners.

PMID- 8998235
TI  - Post-menopausal panic disorder.

PMID- 8998236
TI  - An unusual cause of rhabdomyolysis.

PMID- 8998237
TI  - Granulocyte-colony stimulating factor fails to prevent leucopenia caused by CEMP
      in elderly patients with aggressive lymphoma.

PMID- 8998238
TI  - Total intravenous or inhalational anaesthesia--a cost comparison.

PMID- 8998239
TI  - A complication with a pulmonary artery catheter.

PMID- 8998240
TI  - BAR 1996. XXIV annual Nordic meeting on biological alcohol research. Imatra,
      Finland, 24-26 May 1996. Abstracts.

PMID- 8998242
TI  - Immunoregulation of Asthma II. Proceedings of a symposium. Amsterdam, 23-24 June
      1994.

PMID- 8998241
TI  - Neurodegenerative Disorders: Common Molecular Mechanisms. The Decade of the
      Brain: Midpoint. Proceeding of a symposium. Ocho Rios, Jamaica, April 2-7, 1995.

PMID- 8998244
TI  - Genetic effects on immunity.

PMID- 8998245
TI  - Immunity to infection.

PMID- 8998243
TI  - Uptake and exudation of phenolic compounds by wheat and antimicrobial components
      of the root exudate.
AB  - In the course of our study, it was found that phenyl propenoic acid derivatives
      were readily taken up by wheat. Leaf leachate components were chosen for the
      feeding experiments and p-coumaric acid, ferulic acid and caffeic acid were found
      to be quickly taken up into the plants via the roots. The analytical study
      revealed that the exudate contained potent antimicrobial compounds together with
      amino acids and sugars. Besides the primary metabolites, 4-hydroxystyrene, 3
      methoxy-4-hydroxystyrene and 3-methoxy-4-acetoxystyrene were identified as
      exudate components from wheat roots in sterile hydroponic culture. This indicates
      that these antimicrobial components may play a significant role in the defense
      system as allelochemicals for the rhizosphere.

PMID- 8998246
TI  - HIV.

PMID- 8998247
TI  - Effect of atenolol and reserpine on selected events in the systolic hypertension
      in the elderly program (SHEP).
AB  - The effect of atenolol and reserpine on incidence of strokes, coronary heart
      disease (CHD), cardiovascular disease (CVD), and mortality was assessed in 4736
      persons aged 60 years and older with isolated systolic hypertension. Participants
      were randomized to either chlorthalidone (2371), with step-up to atenolol, or
      reserpine if needed, or placebo (2365). The average baseline SBP/DBP was 170/77
      mm Hg. In the active treatment group, step 1, dose 1 was chlorthalidone, 12.5
      mg/day; dose 2 was 25 mg/day. For step 2, dose 1 was atenolol 25 mg/day (or
      reserpine 0.05 mg/day if atenolol was contraindicated); dose 2 was 50 mg/day
      (reserpine, 0.10 mg/day). During 4.5 years average follow-up, 32% (757) of the
      active treatment group were on atenolol, with an average exposure of two years
      and 8% (193) were on reserpine with an average exposure of 1.7 years. Overall
      there were 96 strokes, 140 CHD events and 289 CVD events among the 2365 active
      group participants. Using time-dependent lifetable regression with adjustment for
      several variables, the addition of either atenolol or reserpine to chlorthalidone
      did not substantially alter the risk ratios for chlorthalidone alone. The
      relative risk for CHD events for atenolol versus no atenolol was 1.04 (95%
      confidence interval: 0.58, 1.86) and for reserpine versus no reserpine was 0.93
      (95% confidence interval: 0.29, 2.96). The relative risk for atenolol were 0.84
      (95% confidence interval: 0.54, 1.30) for death, 1.34 (95% confidence interval:
      0.80, 2.28) for stroke, and 1.07 (95% confidence interval: 0.71, 1.61) for CVD.
      For reserpine, the corresponding relative risks and confidence intervals were
      0.65 (0.26, 1.59) for death, 0.27 (0.04, 2.26) for stroke, and 0.55 (0.20, 1.49)
      for CVD. Thus, the beneficial effects in several outcomes in Systolic
      Hypertension in the Elderly Program (SHEP) were due to the treatment regimen of
      lowering blood pressure based on low-dose chlorthalidone (plus atenolol or
      reserpine as required to meet blood pressure criteria). Additional (independent)
      benefits attributable to atenolol or to reserpine were not identified. However, a
      greater number of patients might have been necessary to adequately evaluate
      potential differential effects of these drugs, especially for reserpine.

PMID- 8998249
TI  - Gender-specific cardiovascular adaptation due to circadian blood pressure
      variations in essential hypertension.
AB  - To determine the effects of circadian variation in arterial pressure on early
      hypertensive target organ disease, we examined systemic hemodynamics (cardiac
      output by indocyanine green dye dilution), renal hemodynamics (renal plasma flow
      by iodine-131 para-aminohippuric acid clearance), left ventricular structure and
      function (2D-guided M-mode echocardiogram), and 24-h ambulatory blood pressure in
      20 women and 46 men with untreated essential hypertension. Both gender groups
      were subdivided into "dippers" and "nondippers" according to the physiologic
      nocturnal decrease in mean arterial pressure by 10% of daytime values. Systemic
      and renal hemodynamics, neurohumoral findings (norepinephrine, epinephrine,
      dopamine, plasma renin activity), causal blood pressure values, duration of
      hypertension, and body weight did not differ between the two groups. In contrast,
      left ventricular mass and mass index was higher in female nondippers than dippers
      (255 +/- 68 v 184 +/- 81 g, and 137 +/- 30 v 102 +/- 39 g/m2, P < .05,
      respectively), while in men no significant differences were found (234 +/- 48 v
      240 +/- 54 g, and 119 +/- 27 v 121 +/- 13 g/m2, P = NS, respectively). Relative
      wall thickness (0.45 +/- 0.06 v 0.39 +/- 0.06, P < .05) and posterior wall
      thickness (1.1 +/- 0.1 v 0.89 +/- 0.2 mm, P < .05) were also found to be greater
      in female nondippers than in dippers, whereas no significant differences were
      obtained in men. Thus, the degree of left ventricular hypertrophy correlated with
      the circadian blood pressure variations in women only, which indicates that left
      ventricular structure may be more load-dependent in women than in men with
      essential hypertension.

PMID- 8998248
TI  - Antihypertensive effects of amlodipine and hydrochlorothiazide in elderly
      patients with ambulatory hypertension.
AB  - Recent studies and authorities have advocated the use of low-dose thiazide
      diuretics as first-line treatment agents in elderly hypertensives. However, these
      recommendations were based solely on blood pressure (BP) measured in the clinic.
      The objective of the present 32-week double-blind study was to compare the
      effects of hydrochlorothiazide (HCTZ) and amlodipine (AML) in elderly patients
      with confirmed ambulatory hypertension. After a 4-week placebo washout period, 42
      (25 men, 17 women) patients (mean age, 69 years) with clinic sitting diastolic BP
      of 95 to 114 mm Hg and daytime ambulatory diastolic BP of > or = 90 mm Hg were
      randomized double-blind to receive AML 5 to 10 mg (n = 21) or HCTZ 12.5 to 25 mg
      (n = 21) once daily. After 8 weeks of monotherapy, patients in whom clinic
      diastolic BP remained > or = 90 mm Hg were given combination therapy with the
      other agent. Amlodipine monotherapy induced significant reductions in clinic,
      mean 24-h, daytime and sleep systolic/diastolic BPs whereas only clinic BP
      decreased significantly in patients treated with HCTZ monotherapy. Moreover,
      19/21 versus 8/21 patients on AML and HCTZ monotherapies achieved adequate BP
      control. At the end of the 32-week treatment period, combination therapy in the
      HCTZ group resulted in statistically significant reductions in clinic as well as
      in 24-h, daytime and sleep ambulatory BPs that were similar to those observed in
      the AML monotherapy group. In conclusion, the administration of AML monotherapy
      induced significant reductions in both clinic and ambulatory BPs in elderly
      patients whereas only clinic BP was significantly decreased by HCTZ monotherapy.
      Moreover, the addition of AML to HCTZ in patients inadequately controlled by
      monotherapy has permitted statistically significant decrements in clinic as well
      as in ambulatory BP. Consequently, the results of the present study suggest that
      the use of HCTZ in doses of up to 25 mg daily is inadequate for ambulatory BP
      control in the elderly despite official recommendations.

PMID- 8998250
TI  - Developmental studies demonstrate age-dependent elevation of renin activity in
      TGR(mRen2)27 rats.
AB  - The objective of the present study was to determine the relationship between
      plasma renin levels, and the development of hypertension and cardiac hypertrophy
      in TGR (mREN2)27 hypertensive rats. Systolic blood pressure and left ventricular
      mass index (LVMI) were measured in transgenic heterozygote and normotensive
      Sprague Dawley control rats at 25, 35, 45, 55, 65, and 75 days of age together
      with determinations of plasma active renin and prorenin, and renal and adrenal
      tissue renin, which were assayed at pH 6.5, 7.4, and 8.5. The systolic blood
      pressure and the LVMI of the transgenic rats were significantly increased
      compared to control rats by 55 and 65 days of age, respectively. Plasma active
      renin of the transgenic rats, measured at physiological pH, was significantly
      higher from 55 days of age, increasing in parallel with blood pressure and
      remaining significantly higher than controls at all age groups tested. Assays of
      both plasma and adrenal renin at various pHs showed a profile of angiotensin I
      generation that matched mouse renin more closely than that of rat renin. The
      ratio of angiotensin I (Ang I) generation at pH 8.5 and pH 6.5 was 0.5 for normal
      rat plasma but was between 3 and 5 for mouse plasma. Plasma prorenin and adrenal
      tissue renin from transgenic rats exhibited a pH profile consistent with the
      major portion being mouse renin. However, the low level of kidney renin observed
      in the transgenic rats exhibited a pH ratio (8.5/6.5) identical to that of normal
      rat renin (0.5), suggesting that residual renin within the kidney was
      predominantly of rat origin. These data indicate that plasma renin levels closely
      parallel the development of high blood pressure and LVMI and show that
      interpretation of the renin status of this strain is critically dependent on the
      assay conditions used. Under the conditions used in this study it was found that
      the TGR(mRen2)27 rat is a high mouse plasma renin model of hypertension.

PMID- 8998251
TI  - The effects of angiotensin II receptor blockade with losartan on systemic blood
      pressure and renal and extrarenal prostaglandin synthesis in women with essential
      hypertension.
AB  - The major antihypertensive effect of losartan, a nonpeptide angiotensin II
      antagonist, is thought to be due to inhibition of the pressor effects of
      angiotensin II. It is possible, however, that losartan alters the synthesis of
      vasodilator or vasoconstrictor prostaglandins (PG), thus contributing to its
      antihypertensive effect. Sixteen postmenopausal women with essential
      hypertension, with a mean age of 59 years and diastolic blood pressures of 95 to
      115 mm Hg, were enrolled in a 12-week, single-blind study to determine the
      effects of losartan on blood pressure, renal and extrarenal PG production, plasma
      renin activity (PRA), plasma aldosterone, and routine biochemical parameters. The
      subjects received placebo during weeks 1 to 4, 50 mg losartan daily during weeks
      5 to 8, and placebo during weeks 9 to 12. During the 4-week treatment period,
      there were no significant, sustained changes in renal or extrarenal synthesis of
      PGE2, PGI2, or thromboxane A2. Losartan significantly reduced systolic blood
      pressure from 155 +/- 11 mm Hg (mean +/- SD) to 139 +/- 13 mm Hg (P = .001) and
      diastolic blood pressure from 100 +/- 2 mm Hg to 87 +/- 5 mm Hg (P < .001)
      despite the fact that the majority of patients had low PRA. Plasma aldosterone
      concentration decreased from 9.7 +/- 6.5 ng/dL to 5.1 +/- 3.9 ng/dL (P = .002)
      and serum uric acid declined from 4.6 +/- 0.8 mg/dL to 4.2 +/- 0.8 mg/dL (P =
      .018) after 4 weeks of treatment with losartan. We conclude that 1) losartan
      decreases blood pressure in women with essential hypertension and low plasma
      renin activity; 2) the antihypertensive effect is not associated with sustained
      changes in renal or extrarenal PG production; and 3) losartan reduces plasma
      aldosterone and serum uric acid concentrations in patients with essential
      hypertension.

PMID- 8998252
TI  - Caffeine elevates blood pressure response to exercise in mild hypertensive men.
AB  - The present study examined the effects of caffeine on blood pressure (BP)
      regulation in hypertensive men during exercise. Twenty unmedicated, mild
      hypertensives (HT, BP = 140/90 to 160/105 mm Hg) and 12 age-matched,
      normotensives (NT, BP < 130/80 mm Hg) performed 30 min of extended bicycle
      exercise following a single dose of caffeine (3.3 mg/kg, equivalent to 2 to 3
      cups of coffee) and placebo in a double-blind, cross-over design. Hemodynamic
      measurements were made at predrug, 40-min postdrug and during exercise. At
      predrug baseline, HT had significantly higher HR (67 v 57 beats/min) and BP
      (141/96 v 118/72 mm Hg) than NT. At postdrug baseline, caffeine increased
      systolic and diastolic BP, and peripheral vascular resistance (P < .01 in all
      cases), decreased HR (P < .05) and did not significantly change stroke volume and
      cardiac output for both groups. During exercise, HR response was greater on
      caffeine day than placebo day in HT (P < 0.05) only. Systolic BP was consistently
      elevated on caffeine day compared to placebo day in both groups (P < .001).
      Diastolic BP was elevated in HT for 30 min of exercise on caffeine day, but this
      pressor effect disappeared at 15 min of exercise in NT. As a result, rate
      pressure products were significantly higher on caffeine days in HT at postdrug
      and during exercise. On caffeine day, 7 (39%) HT and 1 (8%) NT showed an
      excessive BP response (> 230 for systolic or > 120 for diastolic) during
      exercise. In conclusion, caffeine has significant hemodynamic effects on mild
      hypertensives at rest and during exercise. The increased rate-pressure products
      following caffeine during exercise place a greater workload on the heart, and
      abstinence from caffeine, especially before exercise, may be beneficial for
      persons with hypertension.

PMID- 8998254
TI  - Hypertension and sleep apnea in black South Africans. A case control study.
AB  - Despite relatively consistent findings that patients with hypertension have
      higher than anticipated prevalences of sleep apnea/hypopnea (SAH), inadequately
      controlled factors such as age and obesity have been implicated as possibly
      accounting for these findings. All-night polysomnograms were performed on 20
      hypertensive black South Africans, a group with increased risk for this disease.
      They were matched with a control group of black subjects in respect of age,
      gender, body mass index (BMI), neck circumference and scores on a sleep
      questionnaire. While the groups failed to differ significantly in terms of
      demographic variables, nor in regard to 8/9 anthropometric measures, the
      hypertensive group had a significantly higher apnea/hypopnea index (AHI) (P =
      .01), longer duration of AH (P = .01) and lower mean minimum arterial oxygen
      saturation levels (P = .005). Of the anthropometric measures, only age and neck
      circumference were found to be cofactors for AHI and were accounted for in the
      analysis. Five of the hypertensive patients and two of the controls had an AHI >
      10, giving a prevalence odds ratio of 3 (95% confidence interval: 0.66-14.50).
      The present study appears to be the first in black African subjects and with
      prevalence findings largely comparable to those obtained in other ethnic groups.
      There was a trend for more severe SAH to occur in this subgroup of five
      hypertensives (AHI = 14-30) than in controls (maximum AHI = 12). While data are
      lacking to link antihypertensive medication to SAH in humans, further study is
      necessary before discarding this factor.

PMID- 8998253
TI  - A new adenosine subtype-1 receptor antagonist, FK-838, attenuates salt-induced
      hypertension in Dahl salt-sensitive rats.
AB  - We investigated the effects of the adenosine type-1 receptor antagonist FK-838 on
      salt-induced hypertension in Dahl-Sea salt-sensitive (Dahl S) rats. Dahl S rats
      fed a high-salt (4% NaCl) diet for 4 weeks were treated with FK-838 or
      hydrochlorothiazide for 4 weeks and alterations in kidney function and
      morphologic changes were assessed. FK-838 attenuated the development of
      hypertension in Dahl S rats, and caused a decrease in aortic weight in a dose
      dependent fashion. The adenosine antagonist did not produce any detectable
      metabolic disturbance. The blood pressure reduction by FK-838 was associated with
      attenuation of glomerular and arterial injury in the kidney. The renal protective
      effect of FK-838 treatment was associated with a reduction of plasma renin
      activity and plasma aldosterone concentration. In contrast, the thiazide
      diuretic, which produced almost the same blood pressure reduction as FK-838, did
      not attenuate renal damage. These data indicate that adenosine A1 receptor
      antagonism reduces salt-induced hypertension and the consequent renal injuries.

PMID- 8998255
TI  - Power spectral analysis of heart period variability in hypertensive patients with
      left ventricular hypertrophy.
AB  - This study aimed to characterize sympathovagal balance by heart period power
      spectrum analysis in hypertensive patients with echocardiographic evidence of
      left ventricular hypertrophy. Twenty ambulatory patients (11 men and 9 women),
      aged 50 +/- 10 years, with established essential hypertension and
      echocardiographic left ventricular hypertrophy, performed 24-h blood pressure
      monitoring and electrocardiogram Holter recording on 2 consecutive days. Twenty
      age- and sex-matched normal subjects comprised the control group. Power spectrum
      analysis, performed using the fast Fourier transform algorithm, demonstrated
      lower values of low and high frequency power in hypertensives than in controls,
      while ultralow and very low frequency power were similar in the two groups. Very
      low frequency, low frequency, and high frequency power increased during the night
      in both groups, showing a similar circadian pattern. We found a direct
      correlation between daytime systolic (r = 0.51; P < .05) and diastolic (r = 0.52;
      P < .05) blood pressure and left ventricular mass index. Moreover, negative
      correlations were found between left ventricular mass index and low frequency (r
      = -0.47; P < .05) and high frequency power (r = -0.47; P < .05). There was a
      direct correlation between nighttime decrease in systolic blood pressure and
      nighttime increase in high frequency power (r = 0.45; P < .05). As 24-h low
      frequency and high frequency power, obtained using the Fourier transform
      algorithm, both reflect the parasympathetic modulation of heart rate, our results
      demonstrate that hypertensive patients with left ventricular hypertrophy are
      characterized by a sympathovagal imbalance with a reduction of vagal tone that is
      more evident with increasing severity of hypertension.

PMID- 8998256
TI  - Treatment of non-insulin-dependent diabetic hypertensive patients with Ca2+
      channel blockers is associated with increased platelet sensitivity to insulin.
AB  - Insulin influences platelet function by reducing platelet responsiveness to
      vasoactive agonists. In hypertension these insulin-related inhibitory effects are
      blunted. The aim of this study was to determine whether platelet sensitivity to
      insulin is affected after 12 weeks of antihypertensive treatment with calcium
      channel blockers. Eleven patients with essential hypertension and non-insulin
      dependent diabetes were treated with either isradipine or diltiazem. Platelet
      free calcium concentration was measured spectrofluorometrically in nonstimulated
      and in angiotensin II (1 nmol/L)-stimulated platelets that had been pre-exposed
      to insulin (70 microU/mL). Platelets were studied before therapy and after 12
      weeks of treatment. Systolic blood pressure and mean arterial pressure decreased
      significantly during treatment. Both calcium channel blockers equally decreased
      fasting serum insulin levels (from 138 +/- 2.7 pmol/L before therapy to 106 +/-
      9.9 pmol/L after therapy). Results with both calcium channel antagonists were
      similar and have been pooled. In the pretreatment phase, insulin pre-incubation
      had no effect on angiotensin II-stimulated intracellular free calcium and
      responses to angiotensin II were similar in the absence (265 +/- 10.5 nmol/L) and
      presence of insulin (233 +/- 12.1 nmol/L). After treatment with calcium channel
      blockers, insulin significantly (P < .001) reduced angiotensin II-induced rise of
      intracellular free calcium from 214 +/- 7.7 nmol/L (absence of insulin) to 153 +/
      9.3 nmol/L (presence of insulin). Whether these effects are due specifically to
      calcium channel blockers or whether they are the result of lowering of blood
      pressure remains unclear. Serum insulin levels were positively correlated with
      angiotensin II-stimulated increase in intracellular free calcium in platelets pre
      exposed to insulin, (r = 0.46; P < .05) suggesting that with increasing levels of
      insulin resistance, the inhibitory effects of insulin are reduced. This study
      shows that treatment of non-insulin-dependent diabetic hypertensive patients with
      these calcium channel blockers reduces hyperinsulinemia and increases sensitivity
      of platelets to the inhibitory effect of insulin on angiotensin II-stimulated
      calcium responses.

PMID- 8998257
TI  - Color-coded duplex sonography for noninvasive diagnosis and grading of renal
      artery stenosis.
AB  - The accuracy of color-coded duplex sonography (CCDS) in screening hypertensive
      patients for renal artery stenosis (RAS) was assessed using a semi-quantitative
      waveform analysis. Our special aims were to separate between moderate and high
      grade stenoses and to evaluate the accuracy of the method in imaging both the
      whole course of the renal arteries and accessory renal arteries. Included in the
      prospective, angiographically controlled study were 135 consecutive patients with
      268 renal arteries, of which 195 arteries (73%) could be visualized both
      proximally and distally by CCDS. Only three of 15 accessory renal arteries could
      be identified by CCDS. In 42 RAS > or = 50% sensitivity of CCDS was 93%,
      specificity 92%, and overall accuracy 92%. The sensitivity in identifying RAS >
      or = 75% was 92%, and none of the high grade stenoses were missed. Because of
      difficulties in visualizing the middle portion of the renal artery, we carefully
      examined this part of the artery in 116 additional patients. Whereas the proximal
      and the distal parts could be visualized in 77% of the renal arteries, signals
      from the middle third could be derived only in 60% on the right, and in 39% on
      the left side. Provided that the renal arteries were visualized both proximally
      and distally, a hemodynamically effective RAS could be excluded with high
      probability. Moreover, exact grading of high-grade stenoses was possible in all
      cases but one. An advantage of CCDS over conventional duplex sonography appears
      to be the time-saving examination. Since a low prevalence of RAS impairs the
      positive predictive value of CCDS, the examination should be reserved for
      patients with a strong clinical suspicion of renovascular hypertension.

PMID- 8998259
TI  - Effects of discontinuing hormone replacement therapy in patients with
      uncontrolled hypertension.

PMID- 8998258
TI  - Effects of 2,3-butanedione monoxime on blood pressure, myocardial Ca2+ currents,
      and action potentials of rats.
AB  - 2,3-Butanedione monoxime (BDM) has a negative inotropic effect on smooth muscles
      as well as the myocardium. Therefore, in the present study we compared the
      sensitivity to BDM of the cardiovascular system of the spontaneously hypertensive
      (SHR) and the normotensive Wistar-Kyoto (WKY) rat. While BDM significantly
      decreased the blood pressure (BP) for both strains, the SHR was significantly
      more responsive. Specifically, 5, 30, 100, and 200 mg/kg BDM (intravenously)
      reduced BP of the SHR by 9 +/- 3, 20 +/- 3, 49 +/- 5, and 63 +/- 7 mm Hg,
      respectively. The same doses of BDM reduced BP of the WKY by 0, 2 +/- 0.4, 18 +/-
      3, and 26 +/- 3 mm Hg. The duration of the hypotensive effect of BDM was also
      greater for the SHR. In vitro, BDM had a greater suppressant effect on the L-type
      Ca2+ current (ICa(L)) of SHR ventricular myocytes; the IC50 for the suppression
      of ICa(L) was 17 and 29 mM for SHR and WKY ventricular myocytes, respectively.
      The beta-adrenergic receptor agonist isoproterenol antagonized the suppressant
      effect of BDM on ICa(L). Furthermore, BDM significantly reduced the duration of
      both spontaneous and electrically stimulated action potentials of cultured
      neonatal rat cardiomyocytes. Intracellular dialysis with the catalytic unit of
      protein kinase A antagonized BDM's effect on the action potential. These data
      suggest that suppression of myocardial activity contributes to the hypotensive
      effect of BDM. In addition, the elevated response to BDM of SHR cardiac myocytes
      may indicate that the conformation and/or modulation of the L-type Ca2+ channel
      differ for the SHR and WKY lines of rat.

PMID- 8998261
TI  - [Tuberculosis: reemerging disease].

PMID- 8998260
TI  - Comparison of esophageal, tympanic, and forehead skin temperatures in adult
      patients.
AB  - STUDY OBJECTIVE: To compare esophageal, tympanic membrane, and forehead skin
      temperatures in patients undergoing elective surgeries. DESIGN: Prospective
      clinical study. SETTING: Operating room and postanesthesia care unit of a
      tertiary care teaching hospital. PATIENTS: 40 adult ASA status I, II and III
      patients requiring anesthesia and surgery. INTERVENTION: Application of
      crystalline thermometry strips to the forehead of patients. MEASUREMENTS AND MAIN
      RESULTS: Concurrent forehead skin, tympanic membrane, and lower esophageal
      temperatures were measured and compared. The overall bias between esophageal and
      skin temperatures was 0.3 degrees C, between tympanic membrane and skin was 0.5
      degrees C, and between esophageal and tympanic membrane was -0.1 degrees C The
      limits of agreement (precision) between esophageal and skin temperatures were: 
      1.64 degrees C to +2.32 degrees C, between esophageal and tympanic membrane were:
      -1.02 degrees C to +0.74, and between tympanic membrane and skin were: -1.48
      degrees C to +2.52 degrees C. There was no significant relation between the
      change in skin temperature and change in esophageal temperature, whereas there
      was a weak linear relation between change in skin temperature and change in
      tympanic membrane temperature (y = -0.03 + 0.09, r = 0.12). CONCLUSION: There was
      a lack of precision between the clinically accepted measurements (lower
      esophageal and tympanic membranes and the skin temperature measurement. The data
      suggest that forehead skin temperature is not interchangeable with standard core
      temperature measurements, and that sole reliance on the forehead skin measurement
      in the perioperative setting could adversely affect patient care.

PMID- 8998262
TI  - [Vascularization of single thyroid nodule as an indicator malignant neoplasm: a
      study using echo-color-Doppler].
AB  - A number of studies done with color-flow Doppler (CFD) sonography have disclosed
      intense vascularization of malignant thyroid nodules. As this method might be
      able to provide important reference data to enable differentiation between benign
      and malignant nodular pathology, a study of the vascularization of single thyroid
      nodules using CFD sonography was done at the Endocrinology Out-Patient Clinic of
      the Combined Units of the University of Padua and the City Hospital of Venice,
      1st Medical Division. Its aim was to verify the utility of CFD in the diagnosis
      of solitary and scintigraphically "cold" thyroid nodules, particularly to
      distinguish benign from malignant nodular pathology. One hundred nineteen
      patients were examined with hormonal dosage, scintigraphy, fine-needle aspiration
      biopsy (FNAB), echography and CFD sonography of the thyroid, and, in some cases,
      histological examination. Nineteen patients underwent histological examination:
      17 follicular adenomas and 2 papillary carcinomas were found. Color-flow Doppler
      sonography indicated intense intranodular vascularization in both cases of
      malignant neoplasm (sensitivity 100%) and in 2 cases of the 17 benign lesions
      (specificity 88.2%). Moreover, intralesional hypervascularization was not
      observed in the 2 false positive FNAB cases. Although limited by the scarcity of
      histological material and the absence of cases of follicular carcinoma, this
      study has demonstrated that CFD sonography is a highly sensitive (no false
      negatives) and specific (only 2 false positives) method to diagnose
      scintigraphically "cold" single thyroid nodules.

PMID- 8998263
TI  - [Molecular genetics of X-linked primary immunodeficiencies: advances in diagnosis
      and prevention].
AB  - Over the past 2 years, progress in medical genetics has brought about major
      advances in the field of primary immunodeficiencies. The genes underlying four X
      linked defects in humans (X-linked agammaglobulinemia-XLA, X-linked severe
      combined immunodeficiency-XSCID, hyper IgM syndrome-HIGM1, and Wiskott-Aldrich
      syndrome- WAS), have recently been identified. These syndromes are all associated
      with increased susceptibility to infections due to defects of cell mediated
      and/or humoral immunity. The X-linked disorders described here are due to
      mutations in genes whose products are involved in fundamental steps in the
      development and maturation of lymphoid cells. XLA results from a defect in a non
      receptor tyrosine kinase that is likely to be involved in a lineage-specific
      pathway of growth signal transduction. XSCID is due to a defect of the subunit
      gamma, common to a family of multichain lymphokine receptors (i.e., IL-2R; IL
      4R). HIGM1 results from a partial failure of the interaction between T helper
      cells and B cells owing to mutation of the ligand (CD40L) expressed on T cells
      which normally interacts with B cell receptor CD40. The WAS protein has recently
      been identified as the mutated protein in the WAS, although it has not yet been
      fully characterized. Analysis of X-inactivation in different hematopoietic cell
      lineages of carrier females has been done to identify the lineage affected by the
      genetic defect: non random X-inactivation is observed in cell lines where the
      mutated protein plays a fundamental role. Moreover, X-inactivation analysis
      serves as a test to identify obligate carriers and to perform prenatal diagnosis.
      These results have enabled better understanding of the pathogenetic mechanisms
      underlying some immunodeficiencies and have laid the foundation for future
      therapeutic possibilities.

PMID- 8998264
TI  - [Cortisone-resistant bronchial asthma].
AB  - There is general agreement on the inflammatory pathogenesis of bronchial asthma:
      an accumulation of activated eosinophils, degranulated mast cells, T lymphocytes
      and in very severe forms, granulocytes has constantly been found in the bronchial
      mucosa. In allergic bronchial asthma, inflammation seems to be orchestrated
      predominantly by a subset of T lymphocytes, with a phenotype similar to the Th2
      subset able to produce IL-4 and IL-5. Although corticosteroids are the most
      potent therapeutic agents used for this disease, their anti-inflammatory effect
      differs from patient to patient. Some criteria which can be used to define
      steroid-resistant bronchial asthma are listed here. This review analyzes various
      molecular alterations responsible for the deficient response to corticosteroid
      treatment observed in steroid-resistant bronchial asthmatic subjects. New
      knowledge on the mechanism of steroid resistance may have important implications
      for the treatment of chronic asthma and other diseases.

PMID- 8998265
TI  - [Therapeutic ranges of oral anticoagulant therapy in different diseases.
      Guidelines of the Federation of Centers of Surveillance of Patients on
      Anticoagulation. Ad hoc Study Group].
AB  - The "ad hoc" Study Group of the Federation of Italian Anticoagulation Clinics has
      proposed a series of guidelines for oral anticoagulant therapy in different
      pathological states for which this treatment is indicated. These indications are
      based on the scientific literature available through March 1996. While there is
      wide consensus for some indications, opinions diverge regarding others. Finally,
      there are a number of indications which are potentially useful but are not
      supported by adequate studies. For the applications of guidelines in individual
      cases, however, careful clinical evaluation is necessary.

PMID- 8998266
TI  - [Dyslipoproteinemia and monoclonal gammopathy: a case report].
AB  - Type III hyperlipidemia is a rare metabolic disorder characterized by elevated
      plasma concentrations of cholesterol and triglycerides. In subjects homozygous
      for the isoform E2 of apoprotein E, the disease becomes manifest when other
      factors that interfere with normal lipoprotein metabolism are present. Multiple
      myeloma has also been found to be associated with type III hyperlipidemia. We
      report a case with the typical manifestations of the disease (hyperlipidemia and
      palmar xanthoma) in whom the family history and blood analyses excluded
      pathologies potentially interfering with lipid metabolism. On electrophoresis of
      serum proteins, a monoclonal peak was detected. The patient was homozygous for
      the isoform E2 of the apoprotein E. Further blood analyses, bone marrow and
      roentgen examinations enabled the diagnosis of monoclonal gammopathy of
      undetermined origin. The association of type III hyperlipidemia with monoclonal
      gammopathy might be casual, although only the characterization of the antigenic
      determinants toward which the monoclonal antibodies are directed could be
      conclusive. The presence of several family members homozygous for the isoform E2,
      but without the clinical and biochemical characteristics of type III
      hyperlipidemia, and the poor response to diet and drug therapy suggest that
      gammopathy may play role in determining hyperlipidemia.

PMID- 8998267
TI  - [Acute epiglottitis in adults: a rare cause of acute respiratory insufficiency].
AB  - Acute epiglottitis is an infective disease which may have a rapid and aggressive
      course to total upper airway obstruction. Due to its rarity (mostly in adults)
      and aspecific initial clinical features, it may present diagnostic problems to
      less experienced medical personnel. This is the principal reason why the
      mortality rate is still unacceptably high. Indirect or direct laryngoscopy is
      mandatory for diagnosis: as this might be difficult for non-specialist
      physicians, their awareness of the potentially severe consequences of epiglottic
      infections is fundamental to minimizing diagnostic delay. In fact, early
      involvement of experienced ENT and anaesthesiological staff is essential for
      diagnosis, which must be as prompt as possible and followed by thorough clinical
      monitoring to avoid fatal outcome.

PMID- 8998269
TI  - [A case of disseminated bone tuberculosis in an aged patient].
AB  - It is described the case of a 75-year-old woman admitted to the hospital for
      physical degeneration, serious decline in mental status and swelling in the pre
      sternal region. The diagnosis of a severe, destructive and infrequent form of
      disseminated bone tuberculosis was made. This case underscores the risk of
      tuberculosis to which the elderly, in particular, are subject. Moreover, the lack
      of specificity of symptoms and laboratory findings and the presence of
      concomitant chronic pathologies can mask the clinical picture, rendering the
      hypothesis of tuberculosis highly improbable. Computed tomography studies of this
      patient also disclosed the seldom encountered finding of severe bone destruction,
      particularly of the vertebrae and sternum, caused by infiltration of caseating
      granulomas.

PMID- 8998268
TI  - [Therapy of tuberculosis today: to prescribe is not enough. A case report].
AB  - Tuberculosis is a re-emerging disease not only in developing but also in
      industrialized countries. The multidrug resistance of Mycobacterium tuberculosis
      is an increasing problem, mainly due to the poor compliance of the patients on
      drug regimens. The authors discuss the case of a 28-year-old male affected by
      pulmonary tuberculosis who did not improve after a 3-month period of oral
      tuberculosis treatment. The switch to intravenous therapy was rapidly followed by
      clinical and microbiological improvement. The patient subsequently admitted that
      he had not complied with oral treatment because after healing he would be sent
      back to prison. This case demonstrates that, even in the hospital setting,
      noncompliance to antitubercular therapy is not unfrequent, as demonstrated by
      other case reports. The authors discuss a great amount of literature that
      strongly supports the introduction of directly observed therapy for the treatment
      of all tuberculosis patients.

PMID- 8998271
TI  - Neuropsychological differences between schizophrenic patients with heterogeneous
      Wisconsin Card Sorting Test performance.
AB  - This report compares neuropsychological test results of schizophrenic patients
      with good (5-6 categories achieved) and poor (0-1 categories achieved)
      performance on the Wisconsin Card Sorting Test (WCST). It was found that the
      subjects with poor performance also had substantial deficits on the subtests of
      the Wechsler Adult Intelligence Scale-Revised and the Halstead-Reitan Battery.
      The subjects with good WCST performance demonstrated a relatively mild degree of
      impairment on these tests, except for normal performance on the verbal subtests
      of the WAIS-R. It was concluded that: (1) not all schizophrenic patients have
      dense perseverative behavior as identified by impaired performance on the WCST;
      (2) impaired performance on the WCST is accompanied by a variety of other
      cognitive deficits; and (3) there appear to be measures more sensitive to
      cognitive dysfunction in schizophrenia than the WCST.

PMID- 8998270
TI  - [Characteristics of hospitalization of aged patients before and after
      introduction of the prospective payment (DRG-ROD system). Researchers of the
      Italian Group of Pharmaco-epidemiology in the Aged (GIFA)].
AB  - Using data collected by the Italian Group of Pharmacoepidemiology in the Elderly
      (Gruppo Italiano di Farmacoepidemiologia nell' Anziano-GIFA) from 1988 to 1995,
      we analyzed the variation of the most important characteristics of Italian
      hospitalized patients, such as length of hospital stay, appropriateness of
      hospital admission, in-hospital mortality, Charlson's comorbidity score. A number
      of quality of care indexes such as readmission rate, independence in daily
      activities at discharge, waiting periods for a specific instrumental examination
      or specialist consultation, were also analyzed. We studied the variations of
      these parameters in this population after the Diagnosis Related Groups (DRGs)
      system of payment was introduced. This analysis shows that in Italy factors
      related to hospital organization, and not patients, pathobiological
      characteristics, are the chief determinants of length of hospital stay.

PMID- 8998272
TI  - Memory deficits in subsyndromes of chronic schizophrenia.
AB  - Recent psychopathological studies consistently identified a delusional, a
      negative, and a disorganized subsyndrome in chronic schizophrenia. The aim of the
      present study was to investigate these subsyndromes with respect to declarative,
      procedural and working memory deficits. While the delusional subsyndrome was
      associated with an impaired delayed recognition, the negative subsyndrome showed
      a marked deficit in delayed recall. In addition, the delusional and the negative
      subsyndrome shared procedural memory changes. The disorganized subsyndrome was
      associated with neurological soft signs and a poor working memory performance.
      These results do not seem to be effected by severity of illness, degree of
      chronicity, nor attentional deficits. Our findings support the differentiation of
      three subsyndromes in chronic schizophrenia and suggest that memory impairment in
      schizophrenia may reflect the involvement of different memory systems rather than
      an unspecific, global deficit.

PMID- 8998273
TI  - Neuropsychological functioning among the elderly nonpsychotic relatives of
      schizophrenic patients.
AB  - In our prior work with a young sample (age < 60), we showed that three
      neuropsychological functions were impaired among relatives of schizophrenic
      patients: abstraction, verbal memory, and auditory attention. In the present work
      we show that these results do not generalize to an older sample aged 60 years and
      greater. Thus, although we and others have put forth measures of
      neuropsychological function as indicators of the schizophrenia genotype, the
      present study suggests that conclusions may be limited to non-elderly samples.
      Further work is needed to address this issue definitively.

PMID- 8998274
TI  - Olanzapine and fluperlapine mimic clozapine in preventing MK-801 neurotoxicity.
AB  - Antagonists of the N-methyl-D-Aspartate (NMDA) subtype of glutamate receptor
      (e.g., phencyclidine, ketamine, MK-801) cause a schizophrenia-like psychosis in
      humans and neurotoxicity in the adult rat brain. We report here that clozapine
      and structurally related agents (olanzapine, fluperlapine, loxapine, amoxapine)
      can prevent NMDA antagonist neurotoxicity in the rat with a rank order
      corresponding to their ability to mimic the antipsychotic properties of
      clozapine.

PMID- 8998275
TI  - Lower plasma CC16, a natural anti-inflammatory protein, and increased plasma
      interleukin-1 receptor antagonist in schizophrenia: effects of antipsychotic
      drugs.
AB  - Recently, it was suggested that in vivo activation of the monocytic and T
      lymphocytic arms of cell-mediated immunity (CMI) may occur in schizophrenia and
      that antipsychotic drugs may modify CMI. The aim of the present study was to
      examine plasma soluble interleukin-2 receptor (sIL-2R), soluble
      suppressor/cytotoxic antigen (sCD8), interleukin-1 receptor antagonist (IL-1RA),
      and Clara cell protein (CC16) concentrations in normal controls, nonmedicated
      schizophrenic patients, and schizophrenic patients treated with risperidone or
      loxapine. Plasma concentrations of IL-1RA were significantly higher in
      nonmedicated schizophrenic patients than in normal controls. Plasma CC16 was
      significantly lower in nonmedicated and loxapine-treated schizophrenic patients
      than in normal controls, whereas risperidone-treated patients had plasma CC16
      levels which were not significantly different from normal controls. Plasma CC16
      levels were significantly and positively related to age at onset of
      schizophrenia. Plasma sIL-2R was significantly higher in schizophrenic patients
      who were treated with risperidone than in normal controls and nonmedicated
      schizophrenic patients. The results show that (i) schizophrenia is accompanied by
      an activation of the monocytic arm of CMI (i.e., increased plasma IL-1RA) and
      lower plasma levels of a natural anti-inflammatory and immunosuppressive agent,
      i.e. CC16, and that the latter may constitute a trait market of schizophrenia;
      and that (ii) chronic treatment with atypical antipsychotic agents, i.e.,
      risperidone, may normalize lower plasma CC16 and increase plasma sIL-2R.

PMID- 8998276
TI  - Regulation of [3H] dopamine release from mesolimbic and mesocortical areas of
      guinea pig brain by sigma receptors.
AB  - The role of sigma (sigma) receptors in brain function is poorly defined. They are
      located in limbic areas, including nucleus accumbens (NAC) and prefrontal cortex
      (PFC), both of which are thought to be involved in schizophrenia. Many
      antipsychotics (APs), including haloperidol, bind with high affinity to sigma
      receptors. Dopaminergic hyperactivity in NAC is thought to underlie positive
      symptoms of schizophrenia, while dopaminergic hypoactivity in PFC is thought to
      underlie negative symptoms. Sigma receptors regulate N-methyl-D-aspartate (NMDA)
      stimulated [3H] dopamine ([3H]DA) release in caudate-putamen (CP), the
      neuroanatomical substrate for extrapyramidal side effects resulting from chronic
      AP treatment. In the current study, we investigated whether sigma receptors could
      similarly regulate DA release in mesolimbic and mesocortical tissue, and the
      relative participation of different sigma receptor subtypes in this process. We
      found that, in NAC, regulation of DA release by the prototypical sigma agonist
      (+)pentazocine was mediated predominantly by the sigma 1 receptor, whereas in the
      PFC a portion of the (+)pentazocine effect was likely mediated by the sigma 2
      receptor. We also observed, in both the NAC and PFC, that regulation of DA
      release by the sigma agonist BD737 was mediated primarily by the sigma 1
      receptor. In addition, we determined that (+)pentazocine or BD737 effects on DA
      release were not mediated via opioid receptors, nor the phencyclidine (PCP)
      binding site within the NMDA receptor-operated cation channel, nor by sigma
      receptor effects upon [3H]DA accumulated by noradrenergic terminals in PFC.

PMID- 8998277
TI  - Neurotropic influenza in the developing Balb/c mouse.

PMID- 8998278
TI  - Transient normalization of systolic and diastolic function after support with a
      left ventricular assist device in a patient with dilated cardiomyopathy.
AB  - A 19-year-old man who had fulminant heart failure caused by an idiopathic dilated
      cardiomyopathy was supported with a left ventricular assist device for 183 days
      as a bridge to heart transplantation. At the time of intended transplantation it
      was noted that the patient's heart had returned to normal size, had a normal
      ejection fraction, and was able to maintain normal pressures and flows. In view
      of the apparent recovery of cardiac properties, the left ventricular assist
      device was explanted and the transplantation was not performed. However, the
      heart dilated, ejection fraction worsened, and the patient died of heart failure
      exacerbated acutely by a systemic viral illness. Although such recovery of
      systolic function is uncommon, as use of the left ventricular assist devices
      becomes more widespread other physicians might encounter similar findings and, in
      this regard, they might find our experience useful as they contemplate their
      treatment options.

PMID- 8998279
TI  - [Structure of O-specific polysaccharide from Proteus mirabilis O10, containing a
      new component of O-antigens--L-altruronic acid].
AB  - An acidic O-specific polysaccharide was obtained by mild acid degradation of the
      lipopolysaccharide of Proteus mirabilis O10 and studied after full acid
      hydrolysis and carboxyl reduction by 1H- and 13C-NMR spectroscopy, including two
      dimensional correlation spectroscopy (COSY), H-detected heteronuclear 1H,13C
      multi-quantum coherence (HMQC), and rotating-frame nuclear Overhauser effect
      spectroscopy (ROESY). It was found that the polysaccharide contains 2-acetamido-2
      deoxy-D-glucose, 2-acetamido-2-deoxy-D-galactose, D-galacturonic acid, and L
      altruronic acid, and the following structure of the branched tetrasaccharide
      repeating unit of the polysaccharide was established: [sequence: see text]

PMID- 8998280
TI  - [The role of tryptophan in appearance of adenosine deaminase activity].
AB  - Chemical modification of tryptophan residues with N-bromosuccinimide and their
      photooxidation in the presence of trichloroethanol inhibited the activity of
      adenosine deaminase purified from gray and white matter of calf brain. Only two
      of six modified residues are important for enzyme activity. Preliminary kinetic
      data indicate that these essential tryptophan residues are adjacent to the
      substrate-binding site of the enzyme.

PMID- 8998282
TI  - [Superoxide-producing lipoprotein as a tumor growth suppressing factor,
      increasing the number of leukocytes and accelerating cell division in culture].
AB  - Superoxide-generating lipoprotein was isolated and purified from human serum;
      four intraperitoneal injections of Fe(3+)-activated suprol (150 micrograms/ml)
      increased rat peripheral blood leukocytes only by 8-10% in 24 h. In 3 days after
      inoculation of animals with Pliss lymphosarcoma or M-1 sarcoma, similar
      injections of activated suprol increased leukocyte count up to the numbers in
      healthy animals. Growth of M-1 sarcoma and Pliss sarcoma was decreased by 31 +/-
      4 and 52 +/- 2%, respectively. Activated suprol (15 micrograms/ml) stimulated
      growth of stationary chicken embryonic cell culture by 52.1%. Activated suprol at
      concentrations exceeding 50 micrograms/ml lysed all cells in the culture. Cu,Zn
      superoxide dismutase suppressed suprol-stimulated proliferation of actively
      proliferating culture; not activated (native) suprol did not significantly
      increase leukocyte count, did not suppress tumor growth, and did not stimulate
      growth of cultured cells. The data suggest an important role of superoxide
      radicals in these processes. Inhibition of tumor growth by suprol may be
      associated with tumor DNA degradation by superoxide radicals (tumor DNA is more
      sensitive to O2- because superoxide dismutase activity is significantly lower in
      tumor cells versus normal tissues) and increased resistance of the organism due
      to stimulation of leukopoiesis.

PMID- 8998281
TI  - [Comparative study of the effect of fatty acids and certain spin effectors on
      quaternary structure and spin state of methemoglobin].
AB  - Cysteine beta-93 SH-groups of horse and bovine methemoglobins (metHb) were
      modified by N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)iodoacetamide. Effects of
      pH, F-, CN-, oleic acid, and sodium dodecyl sulfate on spin and conformational
      dynamics of the protein were studied by electron and EPR spectroscopy. Oleic acid
      and CN- had similar effects on both parameters. Relationship between spin and
      conformational transformations of metHb was elucidated. Effect of oleic acid can
      be due to increased conformational mobility of C-terminus of metHb beta-chains.

PMID- 8998283
TI  - [Synthesis and study of immobilized insulin].
AB  - Conjugates of insulin with duck egg-white ovomucoid and soybean trypsin inhibitor
      were synthesized. The conjugates are highly stable to alpha-chymotrypsin
      treatment. Oral administration of insulin-ovomucoid conjugates in rabbits
      significantly lowered blood glucose level unlike administration of insulin
      soybean trypsin conjugate.

PMID- 8998284
TI  - [Phosphorylation of rat brain synaptosomal proteins stimulated by alpha
      latrotroxin].
AB  - alpha-Latrotoxin (LTX) is a presynaptic neurotoxin from black widow spider
      (Latrodectus mactans tredecimguttatus) venom; it causes massive Ca(2+)
      independent neurotransmitter release. The effect of LTX on phosphorylation of
      synaptosomal proteins was studied including synapsin I, synaptotagmin, and
      dynamin. Experiments were performed in Ca(2+)-supplemented medium containing 1 mM
      CaCl2 or nominally Ca(2+)-free medium (without added Ca2+ and EGTA) using intact
      synaptosomes isolated from rat brain and prelabeled with 32P(i). The data
      indicate the exposure of synaptosomes to 10 nM LTX for 10 sec stimulates 32P(i)
      incorporation into synapsin I up to 143% versus control in Ca(2+)-supplemented
      medium and up to 130% in Ca(2+)-free medium. LTX (20 nM) significantly stimulated
      synapsin I phosphorylation (up to 173% versus control) only in Ca(2+)-free
      medium. Under these conditions, dephosphorylation of dynamin was not observed.
      Exposure of synaptosomes to LTX in Ca(2+)-supplemented medium for 10 sec did not
      affect 32P(i) incorporation into synaptotagmin but increase in incubation time up
      to 30 sec results in dephosphorylation of synaptotagmin down to 70% versus
      control level. In Ca(2+)-free medium, LTX stimulates the 32Pi incorporation into
      synaptotagmin (up to 140% versus control) and the effect was not time-dependent.
      Thus, LTX-stimulated neurosecretion in Ca(2+)-supplemented and Ca(2+)-free medium
      requires phosphorylation of synapsin I. Phosphorylation-dephosphorylation cycle
      of synaptotagmin can be important for regulation of recyclization of synaptic
      vesicles.

PMID- 8998286
TI  - [Mutually potentiating effect of joint action of carbacholine and histamine on
      secretion and the isoenzyme spectrum of pepsin from frog gastric mucosa cells].
AB  - Pepsin secretion was studied in vivo in the primary culture of isolated secretory
      gastric mucosa cells of the frog (Rana ridibunda). The injection of animals with
      carbacholin (200 micrograms/100 g weight) or histamine (100 micrograms/100 g
      weight) or addition of the hormones (100 microM) into the incubation medium of
      isolated gastric cells significantly increased pepsin activity. In vitro,
      preliminary addition of the specific antagonists of these hormones to the
      incubation medium (1 microM atropine or 100 microM cimetidine) completely
      suppressed the effects of hormones. The effect of histamine is season-dependent.
      Combined injection or simultaneous addition to incubation medium of isolated
      cells of carbacholin and histamine caused mutual potentiation of their effects.
      In this case, the quantitative response of the cells exceeded the theoretical sum
      of the stimulatory effects of each of these two hormones alone. According to
      electrophoresis, the hormones cause quantitative changes in isozyme spectrum of
      proteolytic enzymes but do not significantly affect their qualitative
      characteristics.

PMID- 8998285
TI  - [Participation of the respiratory system of saccharomycetes yeasts in protection
      against the toxic effect of oxygen].
AB  - Level of malonic dialdehyde, lipid peroxidation, and activities of main
      antioxidant enzymes were studied in respiratory-competent and respiratory
      deficient strains of Saccharomyces cerevisiae yeast. The data confirm the
      hypothesis of V.P. Skulachev that the respiratory system is directly involved in
      the antioxidant defense of the cells.

PMID- 8998287
TI  - [Crystallization of a covalently-linked complex of adrenodoxin and adrenodoxin
      reductase].
AB  - Two forms of mitochondrial adrenodoxin reductase from bovine adrenals and
      recombinant bovine adrenodoxin and adrenodoxin reductase expressed in Escherichia
      coli were isolated, purified to homogeneity and biochemically characterized.
      Recombinant adrenodoxin reductase was expressed as a single polypeptide; its
      retention time on DEAE-Fractogel coincides with the second form (F2) of the
      mitochondrial reductase. Two enzyme forms have similar adrenodoxin reductase
      activities in two types of systems comprising either cytochrome c or cytochrome P
      450 (11 beta) as the terminal electron acceptor. Adrenodoxin and each of two
      reductase forms were cross-linked using 1-ethyl-3-(dimethyl-amino
      propyl)carbodiimide. An effective two-step method for the purification of the
      active heterologous cross-linked complexes is suggested that enables purification
      of the functional complexes to homogeneity. The cross-linked bimolecular complex
      of adrenodoxin and adrenodoxin reductase was crystallized for the first time.

PMID- 8998288
TI  - [Status of lipid metabolism in rabbits, delivered from females with moderate
      alimentary hypercholesterolemia].
AB  - Offspring of rabbits fed with cholesterol diet during pregnancy and/or lactation
      was more sensitive to fat load versus the offspring of rabbits fed with standard
      diet. Such enhancement of hyperlipidemic reaction is predominantly due to the
      enhanced rate of blood cholesterol increase (i.e., secretion of cholesterol
      containing lipoproteins) but not to the decreased rate of cholesterol elimination
      from the blood stream. This was confirmed by monitoring the fate of human low
      density lipoproteins intravenously injected in rabbits. The data indicate certain
      alterations of cholesterol metabolism regulation in the offspring of rabbits with
      alimentary hypercholesterolemia. Hypercholesterolemia of pregnant and lactating
      rabbits is important for the formation of the lipid metabolism in their offspring
      because cholesterol levels in the serum of female rabbits positively correlate
      with the expression of hypercholesterolemic and hypertriglyceridemia reactions of
      their offspring in response to fat load and with kinetic parameters which
      characterize the increase in cholesterol and its elimination from the blood
      stream during fat load.

PMID- 8998289
TI  - [Characteristics of polyphosphatase activity of isolated mitochondria from
      Saccharomyces cerevisiae].
AB  - Saccharomyces cerevisiae mitochondria have a polyphosphatase activity which is
      insensitive to a number of inhibitors of mitochondrial ATPase and pyrophosphatase
      (PPase). Heparin (20 micrograms/ml) and EDTA (0.5 mM) do not inhibit ATPase and
      PPase activities but completely suppressed mitochondrial polyphosphatase
      activity. The mitochondrial polyphosphatase activity is maximal at neutral pH; it
      is inhibited by monovalent cations in the presence of Tris+ (K+ > Na+ > NH4+),
      and stimulated by bivalent metal cations (Co2+ > Mg2+ > Zn2+ > Mn2+). The
      polyphosphatase activity does not significantly depend on polyphosphate chain
      length from 9 to 208 but is more than one order of magnitude higher than activity
      with tripolyphosphate. Some properties of mitochondrial polyphosphatase activity
      differ from the characteristics of polyphosphatases of cell envelope, cytosol,
      vacuoles and nuclei of the same S. cerevisiae strain.

PMID- 8998290
TI  - [Catalytic properties of catalase in microemulsions of surface-active agents in
      octane].
AB  - The rate constants of H2O2 decomposition, interaction of catalase complex I with
      H2O2, and the effective rate constants of catalase inactivation during enzymatic
      catalysis (k(in)) were determined by transformation of complete kinetic curves of
      H2O2 decomposition by catalase in reversed micelles of Aerosol OT (AOT) in octane
      and aqueous solution. Effects of hydration of micelles and AOT, H2O2, and
      catalase concentrations in the micellar systems on each of three kinetic
      constants were investigated. Optimal conditions were found which provide for high
      operational stability and catalytic activity of catalase in micellar systems
      versus aqueous solutions. Stability of catalase enhances (decreased k(in)) in the
      presence of reduced glutathione and ethanol in AOT micelles. In reversed AOT
      micelles, catalase partially dissociates to subunits because their peroxidase
      activity was demonstrable in cumene hydroperoxide-dependent oxidation of
      tetramethylbenzidine. Catalase dissociation to monomers is significantly
      decreased in mixed micelles composed of AOT, Triton X-45, Triton X-100, or Tween
      85 and octanol.

PMID- 8998291
TI  - [Purification and characteristics of Saccharomyces cerevisiae cytosol
      polyphosphatase].
AB  - The polyphosphatase with specific activity of 283 units/mg was purified 3450-fold
      to homogeneity with 3.8% yield from cytosol of Saccharomyces cerevisiae yeast.
      Polyphosphatase is monomeric 40 kD protein. The enzyme hydrolyzes polyphosphates
      of various chain length including tripolyphosphate but ATP, pyrophosphate, and p
      nitrophenyl phosphate are not the substrates. Enzyme activity is maximal at 50
      degrees C and pH 6.5-8.5. Several cations of bivalent metals stimulated the
      enzyme activity 8-66-fold (Co2+ > Mn2+ > Mg2+ > Zn2+ > Fe2+). The enzyme is
      inactive in the presence of Ca2+ or Cu2+. Heparin, antibodies against cell
      envelope polyphosphatase, and Cu2+ or Zn2+ in the presence of Mg2+ are potent
      inhibitors of cytosolic polyphosphatase. Cytosolic polyphosphatase is similar to
      purified cell-envelope polyphosphatase but differs in some properties from
      nuclear, vacuolar, and mitochondrial polyphosphatase of the very same yeast.

PMID- 8998292
TI  - [The university and primary care: reflexions on the current situation].

PMID- 8998293
TI  - [Dear Magi...].

PMID- 8998294
TI  - [Hypertensive patients with poor blood pressure control in clinic. Study using
      ambulatory blood pressure monitoring].
AB  - OBJECTIVE: To describe the characteristics of hypertensive patients with poor
      clinical control of their blood pressure (BP > 140/90 mmHg), by examining the
      level of control indicated by out-patient monitoring of BP (OMBP). DESIGN: An
      observational study with diagnostic intervention. SETTING: Urban health centre.
      PATIENTS: Hypertensive patients > 15 years old, with poor control of their BP and
      on the lists of 11 family doctor practices. INTERVENTIONS: Hypertensive patients
      with their BP > 140/90 mmHg, measured in base conditions with a mercury
      Sphygmomanometer, were studied through a 24-hour OMBP (SpaceLabs 90202-90207).
      Good pressure using OMBP was defined as: BP mean in the monitoring period <
      140/90 mmHg. RESULTS: The study included 247 hypertensive patients (53.8% women,
      age 53); 39.3% treated with drugs. Patients with BP appearing well-controlled
      through OMBP (51%) were mainly women, with less damage to target organs, less
      evolution, less variability and less day and night pressure loads, when compared
      with the hypertensive patients with BP showing poor control in OMBP. No
      significant differences were detected between the two groups for the consumption
      of medicine. CONCLUSIONS: In our survey half the hypertensive patients who
      recorded high BP in the clinic showed their pressure well-controlled when using
      OMBP. A more conservative therapeutic approach is suggested for these cases.

PMID- 8998295
TI  - [Extra-hospital consumption of anti-infective agents in a defined daily doses per
      thousand inhabitants per day].
AB  - OBJECTIVES: To analyse the non-hospital use of drugs against infection (excluding
      antivirals and antimycotics) in the province of Zaragoza during 1994 by means of
      the application of the concept of the defined daily dose (DDD) as a technical
      unit of measurement, and defined daily dose per 1000 inhabitants per day (DID) as
      an indicator to facilitate comparison. DESIGN: A retrospective observational
      study. SETTING: Primary care. PARTICIPANTS: All the prescriptions for medicines
      to combat infection filled outside the hospital (940,662 units) in the province
      of Zaragoza. These following subgroups: J01 Systemic antibiotics, J03 Systemic
      chemotherapy drugs, J04A Tuberculosis, G04A Antiseptic and urinary infection
      drugs and R05C1 Mucolytic and anti-infection expectorants. MEASUREMENTS AND MAIN
      RESULTS: 8.6% of the total medicine prescribed in 1994 were drugs to combat
      infection, with 17.70 DID. The 4 most commonly prescribed subgroups were:
      penicillin, macrolides, tetracycline and cephalosporins. The 10 most commonly
      used active principals were, in descending order: amoxycillin,
      amoxycillin/clavulanic, erythromycin, cotrimoxazol, doxycyclin, cyprofloxacin,
      norfloxacin, roxythromycin, clarithromycin, pipemidic acid. CONCLUSIONS: The use
      of drugs to combat infection in our province is essentially no different from
      what other authors have observed. It would be interesting to carry out a follow
      up study on the use of third-generation fluorquinolones and cephalosporins in
      primary care and to relate use of them to the evolution of resistance to anti
      microbe drugs.

PMID- 8998296
TI  - [Knowledge, attitude and practice in relation with HIV/AIDS infection in high
      school and vocational training in Mieres].
AB  - OBJECTIVE: To find the students' level of knowledge, attitudes and conduct
      concerning HIV/AIDS. INTERVENTIONS: Data-gathering by means of a self
      administered questionnaire. RESULTS: 450 students (60.8%), average age 17, took
      part. 52.9% answered questions on the disease correctly. 48.9% believed they had
      sufficient knowledge/information. More men than women thought they were well
      informed. 89.6% said they would accept someone with AIDS in their class. 65% said
      they were worried about the possibility of being infected. 31.6% said they were
      sexually active. All of these affirmed that they knew of and took preventive
      measures. 83% said they always used a condom, the reason being to avoid
      pregnancy. 0.9% took intravenous drugs, but have never shared syringes. 100% knew
      that this protected them from infection. 42% (more men than women) believed that
      today's youth is changing its life-style because of AIDS. CONCLUSIONS: In spite
      of knowing the basic facts about HIV/AIDS, students have many mistaken ideas.
      They do not think that these facts have given rise to changes in their behaviour.
      These results could be useful for the design of a future health education
      intervention.

PMID- 8998297
TI  - [Utilization of contraceptive methods during the lactation period].
AB  - OBJECTIVES: To find the use of family planning methods during breast-feeding and
      establish whether there is a relationship with social-demographic questions or
      the breast-feeding. Secondly, to evaluate nursing mothers' understanding of these
      methods. DESIGN: An observational, crossover study using a self-administered
      questionnaire. SETTING: Primary care. PARTICIPANTS: 398 women in their 7th month
      of breast-feeding were chosen by simple random sampling from the register of
      births. Reply rate: 85.2%. MEASUREMENTS: The use of contraceptive methods (CM),
      type of breast-feeding, social-demographic characteristics, information received
      and women understanding of family planning (additive Likert-type scale). RESULTS:
      78% of the women interviewed said they used some CM after delivery: barrier
      methods were the most common (63.7%). Use was significantly greater in women with
      a lower level of information or who had previously used CM. CONCLUSIONS: Women
      with a lower level of information or who had used family planning methods
      previously said they used them more during breast-feeding. There is insufficient
      information about contraceptive methods during this period, especially among less
      educated women. Understanding of CM increases when breast-feeding lasts longer.
      Activities performed by health staff are not connected to women better
      understanding of contraception.

PMID- 8998298
TI  - ["White coat" hypertension in primary care. Study using ambulatory blood pressure
      monitoring].
AB  - OBJECTIVES: To analyse whether individuals with white coat hypertension (WCH)
      display clinical features different from those of individuals with essential
      hypertension. DESIGN: A non-randomised, descriptive, crossover study. SETTING:
      Primary care. La Orden Health Centre, Huelva. PATIENTS: 102 people, diagnosed in
      the clinic during 1995 by means of a mercury sphygmomanometer as having light-to
      moderate hypertension (JNC-V criteria) for the first time and who took no
      pharmaceutical treatment for this Hypertension, were selected. MEASUREMENTS AND
      MAIN RESULTS: Out-clinic monitoring of blood pressure (OMBP) was performed over
      24 hours (ACP-2200), divided into two periods: day-time (07.00 to 00.00) and
      night-time (00.01 to 06.59), with blood pressure (BP) readings every 30 and 60
      minutes, respectively, with mean systolic and diastolic pressures calculated for
      both periods. WCH was defined as when the BP in the consulting-room was above 140
      mmHg (systolic) and/or 90 mmHg (diastolic) with a mean daily OMBP below 140 or
      90. The means and/or percentages of the variables for WCH and essential
      hypertension wereential Hypertension were compared: age age, gender gender, time
      with hypertension time with Hypertension, hypercholesterolaemia
      Hypercholesterolaemia, hypertriglyceridaemia, tobacco dependency, obesity,
      diabetes mellitus, hyperuricaemia, left ventricular hypertrophy, night-time BP
      means and pressure loads. CONCLUSIONS: WCH is very prevalent. Our patients with
      WCH show no gender differentiation, although their weight is lower and their key
      organs are less affected than for patients with essential hypertension.

PMID- 8998299
TI  - [The influence of unemployment on mental health problems].
AB  - OBJECTIVE: To evaluate the relationship between unemployment and mental health
      problems. DESIGN: Crossover study, using systematic sampling of medical records.
      SETTING: Health District in the province of Barcelona. PATIENTS AND OTHER
      PARTICIPANTS: 189 medical records from 1,549 unemployed people, and another 189
      paired for age and gender of people in work, were included in the study.
      MEASUREMENTS AND MAIN RESULTS: The unemployed group had between 1.3% and 18.8%
      more people with mental health problems than the in-work group. There were no
      significant differences between the two groups as to their use of primary care
      health services. CONCLUSIONS: It was established that there is a connection
      between unemployment and mental health problems. Prospective studies to follow
      cases might contribute more data on the cause and effect relationship.

PMID- 8998300
TI  - [The consumption of alcohol, tobacco and drugs in adolescents].
AB  - OBJECTIVES: To find how much alcohol, tobacco and drugs adolescents consume and
      identify some linked socio-family variables. DESIGN: A crossover and descriptive
      study, with randomised sampling stratified by classrooms. SETTING: Secondary
      schools in the town of Lugo. PATIENTS AND OTHER PARTICIPANTS: 805 students of
      both sexes from the secondary schools. MEASUREMENTS AND RESULTS: We used a self
      filled anonymous semiclosed questionnaire. 34.6% habitually consumed alcohol, of
      whom 43.3% had got drunk at least once in the previous 6 months and 7.1% on more
      than 13 occasions. 25.7% were habitual smokers. 12.3% had consumed cannabis;
      10.1% tranquilisers; 7.5% amphetamines; 4.6% sleeping pills; 2.1% cocaine; 1.9%
      LSD; 1.5% heroin. Variables linked to consumption were: age, repeating the school
      year, considering him/herself a bad student, fighting, consumption by both
      parents, not doing sports, having more money and not having a good relationship
      with parents. CONCLUSIONS: Adolescent alcohol, tobacco and drug consumption is
      high and similar to other regions of Spain. Prevention strategies are needed, in
      the family, at school and in the media.

PMID- 8998301
TI  - [Impact of an informative feedback process on drug prescription].
AB  - OBJECTIVE: To evaluate the impact of the face-to-face interview and feed-back on
      the prescribing habits of doctors interviewed. DESIGN: Controlled intervention
      study. SETTING: Primary Care area (PCA) of Alt Penedes-Garraf. PARTICIPANTS: 16
      general practitioners (GP). The intervention group (IG) consisted of 8 GPs from
      the county of Garraf; the control group (CG), of 8 from the Alt Penedes.
      INTERVENTIONS: The target doctors were identified by quantitative analysis of GP
      prescription in the PCA in 1993. In June 1994, there was a face-to-face interview
      with the IG doctors. There was no intervention on the CG. MEASUREMENTS AND MAIN
      RESULTS: No statistically significant differences were found, for the overall
      prescription turnover or expenditure generated by the prescriptions, between the
      two groups in the pre-intervention period (p > 0.05). Drugs expenditure decreased
      in the IG versus an increase in the CG. Comparison of the monthly accumulated
      increase revealed containment of drugs expenditure during the 9 months after the
      interview in the IG against the growth in the CG. In addition the number of units
      of medicine of doubtful efficacy (UDE) and unwarranted combinations of medicine
      to combat infection (UCMI) prescribed per doctor went down in the IG, but went up
      in the CG. CONCLUSIONS: The results show a containment in the growth of drug
      expenditure and a decrease in UDE and UCMI prescription by GPs in the IG as
      against the CG. The decreasing effectiveness over time of the one-off
      intervention suggests that there should be regular interventions to ensure a long
      term effect.

PMID- 8998302
TI  - [Usefulness of a school health program for detecting deficits in visual acuity].
AB  - OBJECTIVE: To evaluate the use of the school health programme to detect anomalies
      in visual sharpness. DESIGN: A descriptive, crossover study. SETTING: Puerto Real
      Health Centre (Cadiz). PATIENTS: A random sample of school-children included in
      the school health programme for the first year of EGB (basic) and belonging to
      schools located in the health district. MEASUREMENTS AND MAIN RESULTS: Visual
      sharpness was examined using Snellen's optotypes scale. Out of a sample of 300
      children, 72 cases of deficiency were detected, 50 of them for the first time. Of
      34 children with a previously unidentified deficiency who were surveyed by
      telephone and checked by the ophthalmologist, 22 had the suspected deficiency
      confirmed, treatment being prescribed for 19. This meant a minimum effectiveness
      of 38%, with the cases lost and not checked being considered not confirmed.
      CONCLUSIONS: Despite the limitations of this study, our effectiveness in
      detecting visual sharpness during the school health examination is quite
      acceptable. Therefore, we propose its continuity, incorporating some improvements
      in quality.

PMID- 8998303
TI  - [Factors associated with anxiety and taking psychotropic drugs in caregivers of
      incapacitated patients].
AB  - OBJECTIVE: To identify factors associated with the possibility of suffering
      anxiety and the taking of medicine for psychological reasons by carers for
      disabled patients. DESIGN: A descriptive crossover study. SETTING: Carranque
      Health District, Malaga. PATIENTS AND OTHER PARTICIPANTS: The sample consisted of
      53 carers for disabled patients. Unidentifiable carers, carers incapable of
      replying to the evaluation test and carers for people disabled for less than 6
      months were excluded. MEASUREMENTS AND MAIN RESULTS: Multiple linear regression
      showed significant connection between scoring in the STAI test (State-Trait
      Anxiety Inventory), the availability of support for the carer, and the family
      relationship of the carer and the disabled person. The mean score in the test for
      the 22 carers receiving support was 27.09, against a mean of 34.48 for the 31
      others. The mean score in the STAI when carer and disabled person had a first
      degree family relationship was 33.05, against 27.26 when there was a second
      degree family relationship. STAI scores were higher among the carers taking
      medicine for psychological reasons (38.59). The taking of medicine for
      psychological reasons, analysed by logistic regression, displayed no association
      with any other variable. CONCLUSIONS: The anxiety of the carer is greater when
      he/she has no support and when the disabled person is a close relative.
      Consumption of medicine for psychological reasons is in parallel relationship to
      the STAI anxiety test.

PMID- 8998304
TI  - [How to improve our clinical interviews].

PMID- 8998305
TI  - [Cost of the treatment of iron-deficiency anemia].

PMID- 8998306
TI  - [On the prevention of additional demands].

PMID- 8998307
TI  - [About the nomination and training of family physicians].

PMID- 8998308
TI  - [Children safety in the automobile and health education].

PMID- 8998309
TI  - [Screening for glaucoma in diabetic patients].

PMID- 8998310
TI  - Nutrition and cancer.

PMID- 8998311
TI  - Case report: pneumomediastinum and pneumothorax complicating colonoscopy.
AB  - Colonic perforation is potentially the most serious complication of colonoscopy.
      Both the clinical manifestation and rapidity of onset of symptoms can vary
      depending on whether the perforation occurs directly into the peritoneal cavity
      or into the retroperitoneal space. Colonic perforation is often associated with
      abdominal pain, although more uncommon presentations have been documented. A case
      report of a unilateral pneumothorax and pneumomediastinum complicating
      colonoscopy is described, which responded well to conservative measures without
      recourse to surgical intervention, antibiotic therapy or parenteral alimentation.

PMID- 8998312
TI  - [MR mammography--a critical stocktaking].

PMID- 8998313
TI  - [What is it called? A formulation and glossary for the finding and understanding
      of results in HRCT of the lung].
AB  - In HRCT reports multiple different, often synonymous, German and English terms
      are used. The variety of terms impede understanding and acceptance of HRCT.
      Purpose of this paper is to present a scheme, which is based on the anatomic
      landmarks (secondary lobule), and the density of pathologic changes, as well as a
      glossary from the German HRCT-literature, including suitable terms, definitions,
      synonyms and English terms. Low attenuation changes include emphysemas, air
      filled cavities (bullae, cysts, cavitations, honeycombing) and bronchial
      dilatation, changes with increased density consist of diffuse (ground glass
      opacity, consolidation) and focal processes (reticular and nodular densities).
      Reticular densities are categorised in thickened interlobular septae and
      translobular lines with differentiation of a reticular pattern and curvilinear
      lines. Nodular processes are categorised according to size, density, morphology,
      localisation and distribution. Parenchymal distortion and destruction indicate
      the severity of these processes. Certain patterns are indicative for possible
      differential diagnoses, and a recommendation for further procedures is given.

PMID- 8998314
TI  - [Pulmonary manifestations in rheumatoid arthritis: high-resolution computed
      tomography in correlation with the skeletal changes and the laboratory chemical
      changes].
AB  - PURPOSE: It has been the aim of the following study to evaluate pulmonary changes
      in rheumatoid arthritis with high-resolution CT and to assess their correlation
      with joint manifestation and laboratory parameters. MATERIAL AND METHODS: The
      authors prospectively performed computed tomography (CT) in 83 patients with
      rheumatoid arthritis and graded pulmonary changes for frequency and severity.
      Included were patients with 6-7/7 ARA, BSR > 25/1 min and mean disease duration
      of 12 years (range, 1-44). Data of medical and drug histories, smoking habits,
      blood levels of rheumatoid factor (RF), antinuclear antibodies (ANA) and C
      reactive protein as well as the degree of joint involvement were taken into
      account. RESULTS: 58 patients (70%) had pathological CT scans showing the
      following abnormalities: interlobular thickening (44.5%), intralobular thickening
      (34%), nonseptal linear attenuation (35%), nodular or linear pleural thickening
      (32.5%), ground-glass pattern (19%), centrilobular nodules (13%), honeycombing
      (13%) and bronchiolectasis (9%). Intralobular thickening, honeycombing and
      pleural thickening were associated with a higher degree of joint manifestation;
      pleural thickening, honeycombing and ground-glass pattern were associated with a
      higher level of rheumatoid factor. There was no relationship between pulmonary
      changes and either the duration of the disease, antinuclear antibodies (ANA) or C
      reactive protein. CONCLUSION: CT may be a useful noninvasive tool for recognition
      of RA-associated lung disease. Interstitial lung changes are frequent and they
      are independent of the duration of the disease. Pulmonary interstitial changes
      are more frequent and more severe in RF-positive patients and in case of more
      severe joint involvement.

PMID- 8998315
TI  - [Intravenous spiral CT angiography for assessment before orthotopic liver
      transplantation: comparisons between tomography, MIP, 3-dimensional surface
      imaging and intra-arterial DSA].
AB  - To analyse the efficacy of intravenous spiral CT angiography (SCTA) for the
      evaluation before orthotopic liver transplantation (oLT) compared with DSA.
      METHODS: Spiral CT was performed on 31 potential recipients of a liver graft in
      order to examine hepatic vessels, coeliac axis, splenic artery and superior
      mesenteric artery. The arterial vessels were reconstructed in "Maximum Intensity
      Projection (MIP)" and "Shaded Surface Display (SSD)"-technique. The axial images,
      MIP and SSD were compared in 25 patients with DSA with regard to the
      visualisation of the vascular anatomy, detectability of stenosis and vascular
      diameters. RESULTS: The type of arterial liver supply could be determined via
      SCTA in all patients. Stenosis of the coeliac axis was seen in ten patients on
      the DSA, MIP and SSD and in eight patients on the axial images. Occlusion of the
      hepatic artery was clearly visualised in two patients on the DSA, axial images
      and MIP and in one patient on the SSD. There was no false positive diagnosis with
      SCTA. SSD was seen as the best technique to visualise the vessels without
      overshadowing. There were no significant differences between the diameters
      measured from the axial images, MIP and SSD images in transversal direction and
      the DSA images (p > 0.05). CONCLUSION: SCTA is a greatly promising method for the
      imaging of vessels supplying the liver before oLT, and may convey more diagnostic
      information than DSA.

PMID- 8998316
TI  - [The morphology and incidence of maxillary sinus septa].
AB  - AIM: The variations and frequency of bony septa in the paranasal sinuses were
      studied prospectively by means of computed tomography. PATIENTS AND METHODS: The
      presence and morphology of the septa in the paranasal sinuses were studied in 100
      consecutive non-selected adults. RESULTS: CT examinations of 200 maxillary antra
      showed variations in 26 (13%). There were one complete septum (0.5%), 18
      incomplete septa at the base of the antrum (9%) and 7 incomplete septa situated
      anteriorly (3.5%). CONCLUSION: Bony septa in the sinuses may be clinically
      relevant during sinus endoscopy or tooth implantation. Preoperative examination
      may reduce the complication rate of these procedures.

PMID- 8998317
TI  - [CT osteodensitometry in the area immediate to hip endoprostheses].
AB  - The value of metal artifact reduction in quantitative bone density determination
      in the vicinity of metallic implants was studied. METHOD: Ten cadaver femora with
      hip endoprostheses implanted intra vitam were examined in CT with varying slice
      thicknesses, tube voltage, scan time and magnification factor. The artifact-laden
      images were then processed using a metal artifact reduction programme (MAR). The
      metallic implant was removed, allowing the bone slices to be examined again with
      the same imaging parameters, but without the bothersome metal artifacts. This
      allowed comparison of bone density values obtained before and after application
      of MAR with data obtained after implant removal. RESULTS: A comparison of the
      bone density measurements between the sample group without implants and the group
      with indwelling implants prior to MAR showed an unexpected correlation
      coefficient r = 0.975-0.977. The correlation coefficients after MAR rose to r =
      0.987-0.992 in 125 kV and r = 0.989-0.991 in 85 kV modes. The reproducibility of
      the density measurements for the groups without implants and with implants
      following MAR showed variation coefficients (VC) of 1.16% and 0.75% respectively.
      The reproducibility of the manual definition of the region of interest (ROI) in
      bone showed a VC = 2.19%. CONCLUSIONS: Bone density in the vicinity of metallic
      implants can be reliably and reproducibly determined using MAR.

PMID- 8998318
TI  - [The efficacy of lead shielding in patient dosage reduction in computed
      tomography].
AB  - PURPOSE: Investigation of the efficacy of lead apron, testis capsule and thyroid
      collar for dose reduction in uterus, ovaries, testes and thyroid gland in
      computed tomography examinations. METHODS: At an Alderson-Rando phantom dose of
      uterus, ovaries, testes and thyroid gland was measured with thermoluminescent
      dose meters. CT of the upper abdomen, the whole abdomen and the skull were
      simulated without and with lead shielding. As lead shielding, a lead apron was
      attached around the pelvis of the phantom in case of CT of the upper abdomen, a
      testis capsule was used in CT of the whole abdomen and a thyroid collar in CT of
      the skull. RESULTS: In CT of the upper abdomen the lead apron did not lead to any
      recognisable dose reduction in uterus and ovaries. In CT of the whole abdomen the
      testis capsule led to a dose reduction in testes of 95% (1.39 mSv) and in CT of
      the skull the thyroid collar to a dose reduction in thyroid gland of 23% (0.19
      mSv). CONCLUSIONS: In abdominal CT examinations the testis capsule is an
      important instrument to reduce the dose of the testes whereas the lead apron is
      not appropriate for a dose reduction in the uterus and ovaries. In CT of the
      skull the thyroid collar can remarkably reduce the scattered radiation exposure
      of the thyroid gland and should be recommended.

PMID- 8998319
TI  - [MR diagnosis after a Ross operation].
AB  - PURPOSE: To determine the ability of MRI to diagnose morphological and functional
      changes in patients after Ross procedure. MATERIAL AND METHODS: During one year,
      5 patients after Ross procedure were studied by MRI. T1-weighted spin-echo
      sequences in different orientations as well as cine sequences and a VENC sequence
      were used. RESULTS: In all patients the morphology including the postoperative
      changes could be visualised by MRI. The cine sequences provided functional
      information on valvular and ventricular function. VENC-MR yielded an exact
      quantification of the regurgitant fraction. CONCLUSION: MRI is capable of
      providing all important diagnostic information in patients after Ross procedure
      such as valvular and ventricular function and valvular and outflow tract
      morphology in a single examination.

PMID- 8998320
TI  - [Age-dependent MR imaging of the tibia in children up to 2 years old. The
      findings in children without bone marrow-relevant diseases or therapies].
AB  - PURPOSE: Since the beginning of bone marrow conversion presents with substantial
      differences as shown by anatomical or magnetic resonance studies, the purpose of
      this study was to demonstrate via MRI an age-dependent bone marrow conversion of
      the tibia in children of up to two years of age. METHODS: We studied the bone
      marrows of the tibia in 24 children ranging from one month to two years by means
      of MRI. T1-weighted SE-sequences were used. Children who suffered from diseases
      affecting the bone marrow were excluded. A retrospective analysis of the MR
      images was performed. RESULT: A gradual increase of signal intensity could be
      demonstrated in the epiphyses and the diaphysis of the tibia beginning shortly
      after birth. During the first two years of life a further increase of signal
      intensity could be observed in these regions, progressing through metaphyses up
      to the growth plates. CONCLUSION: First signs of bone marrow conversion can be
      detected in the tibia shortly after birth. Bone marrow infiltration in the tibia
      is expected to be recognised by MRI from this time onward.

PMID- 8998321
TI  - [Initial experiences with pulsed fluoroscopy on a multifunctional fluoroscopic
      unit].
AB  - PURPOSE: Comparison of radiation doses in pulsed and continuous fluoroscopy to
      quantify the dose reduction by pulsed fluoroscopy. Further, the applicability of
      pulsed fluoroscopy in clinical routine has been evaluated. MATERIALS AND METHODS:
      In a human pelvic phantom, the radiation dose (skin entry dose in cGycm2) was
      measured at two pulses per second (pps), 3 pps, 6 pps, 12 pps and continuous
      fluoroscopy mode, respectively, using image-intensifier entries of 38 cm, 25 cm,
      and 17 cm. 300 examinations were carried out, and the results of the different
      fluoroscopy modes were registered. RESULTS: Dose reduction depends on the image
      intensifier entry. Compared to the radiation dose in continuous fluoroscopy, with
      12 pps fluoroscopy the radiation dose can be reduced at a minimum of 51%, with 6
      pps fluoroscopy to 40%, with 3 pps fluoroscopy to 20%, and with 2 pps fluoroscopy
      to a minimum of 14.5%. Clinical routine has shown that 78% of all examinations
      can be performed with 2 or 3 pps fluoroscopy mode. In 12.7% of the cases pulsed
      fluoroscopy of diverse frequencies was used, in an additional 2% combined with
      continuous fluoroscopy. Exclusively, continuous fluoroscopy has been employed in
      2% of the cases. CONCLUSIONS: Using pulsed fluoroscopy, an 80% reduction of the
      radiation dose compared to continuous fluoroscopy is possible. About 96% of all
      examinations can be performed with pulsed fluoroscopy of different pulse rate and
      without using continuous fluoroscopy.

PMID- 8998322
TI  - [The diuresis urogram in patients with a bladder replacement].
AB  - PURPOSE: To differentiate between urodynamically relevant obstruction and
      functionally unimportant dilation of the upper urinary tract in patients with
      neobladder using a modified furosemide urogram. METHOD: An excretory urogram with
      furosemide loading was carried out in 19 patients with neobladder and
      sonographically and urographically confirmed dilation of the upper urinary tract.
      Once strong contrasting of the renal pelves and calyces has been achieved, 20 mg
      of furosemide were applied and late radiographs were obtained at 15 min and 30
      min, respectively. An obstruction was defined as increasing dilation of the renal
      pelves and calices during forced diuresis and lack of washout effect of the
      contrast medium. RESULTS: In 32 cases, the renoureteral unit (RUU) was dilated on
      ultrasound. Of these, 25 RUU's showed good emptiness of contrast medium upon
      stimulation of diuresis, six RUU's returned a borderline findings, while one RUU
      was found to exhibit a decompensated anastomotic stenosis, which was dilated. Two
      further patients with borderline findings were later treated surgically due to
      their pain symptoms. No patient required further preoperative diagnostic
      procedures. CONCLUSIONS: The modified furosemide urogram represents a cost
      effective diagnostic orientation strategy in patients with neobladder and dilated
      renal pelves and calyces and is both well-tolerated by patients and meets with
      broad acceptance from the urologic staff.

PMID- 8998323
TI  - [The color Doppler-guided compression therapy of pseudoaneurysms. The authors'
      own experiences and a review of the literature].
AB  - PURPOSE: The common use of interventional angiographic techniques and the
      sensitive detection of this vascular complication by ultrasound are major factors
      contributing to the increasing incidence of femoral artery pseudoaneurysms.
      ultrasound-guided compression repair of femoral artery pseudoaneurysms was
      prospectively evaluated. MATERIAL AND METHODS: 11 femoral artery pseudoaneurysms
      were detected in 10 patients who ranged from 45 to 79 years of age. In one
      patient two ipsilateral pseudoaneurysms occurred. All patients were considered to
      be candidates for ultrasound-guided compression repair. RESULTS: Successful
      compression repair was achieved in 9 of 11 pseudoaneurysms (82%) with a mean
      diameter of 2.2 +/- 1.0 cm. In two recurrent lesions (22%) definitive thrombosis
      required a second treatment. Compression was maintained between 10 and 40 minutes
      (mean 22 +/- 11 minutes). No complications have been observed. CONCLUSIONS:
      Ultrasound-guided compression repair provides an efficient, noninvasive and safe
      treatment of femoral artery pseudoaneurysms. More than 80% of pseudoaneurysms can
      be occluded successfully. In recurrent lesions a second attempt is valuable.

PMID- 8998324
TI  - [Catheterization of the nasolacrimal duct].
AB  - A technique is described for passing a guide wire through the lacrimal duct into
      the nose following catheterisation of the duct. The wire is passed into the
      pharynx, a 7 F feeding tube is passed through the nose into the pharynx and these
      are then pulled out of the mouth with a Magill forceps. The tip of the feeding
      tube is then cut off and the guide wire introduced into a side hole of the
      catheter. By removing the catheter, the tip of the guide wire is pulled along and
      can be removed from the nose.

PMID- 8998326
TI  - Choledochal cyst misinterpreted as a biloma after a blunt abdominal trauma.

PMID- 8998325
TI  - [Metastatic pulmonary calcification as a rare complication of terminal kidney
      failure: the x-ray and CT findings].

PMID- 8998327
TI  - [The Swyer-James syndrome: its imaging with high-resolution computed tomography].

PMID- 8998328
TI  - [Arteriovenous lung fistula as a pulmonary complication of biliary cirrhosis].

PMID- 8998329
TI  - [Spinal cord compression by extramedullary hematopoiesis in thalassemia major].

PMID- 8998330
TI  - [Ultrahigh-dosage urokinase lysis during pulmonary embolism prophylaxis by means
      of an extractable caval filter].

PMID- 8998331
TI  - [Parathyroid hormone-calcium system in the functional activity of the hypothalamo
      neurohypophyseal complex].

PMID- 8998332
TI  - [Decreased pain sensitivity in man after treatment with superlow doses of
      oxytocin].

PMID- 8998333
TI  - [The role of binding activity of hematopoietic microenvironment cells in the
      recovery of various hematopoietic stems inhibited by cytostatics].

PMID- 8998334
TI  - [Phlogogenic and hematopoiesis-stimulating activity of liver and lung macrophages
      during liver regeneration].

PMID- 8998335
TI  - [Para=aminobenzoic acid as a stimulator of angiogenesis].

PMID- 8998337
TI  - [Stimulation by exogenous zinc-metallothionein of DNA replicative synthesis and
      proliferation of bone marrow cells in mice].

PMID- 8998336
TI  - [The effect of garlic preparation alisat on the level of lipid peroxidation
      products, activity of various antioxidant enzymes, and blood level of
      lipoproteins in patients with atherosclerosis].

PMID- 8998338
TI  - [The use of anti-idiotypic antibodies for correction of autoimmune response to
      brain protein S-100].

PMID- 8998339
TI  - [On a mechanism of histamine-liberating effect of radiocontrast media].

PMID- 8998340
TI  - [Comparative anti-arrhythmia activity of rinocaine and lidocaine].

PMID- 8998341
TI  - [Effect of adrenocorticotropic hormone fragments and atriopeptides on the
      development of toxic brain edema-swelling].

PMID- 8998342
TI  - [The effect of antiandrogens cyproterone acetate and niftolide on free radical
      oxidation indices in model biological systems in vitro].

PMID- 8998344
TI  - [Thrombolytic and antithrombotic effects of low molecular weight heparin
      serotonin complex].

PMID- 8998343
TI  - [Study of the analgesic effect of the semax preparation].

PMID- 8998345
TI  - [Culturing of interspecies hybridomas in immunologically tolerant animals].

PMID- 8998347
TI  - [Changes in immunological reactivity of C57Bl/6 mice during the zoosocial
      conflict].

PMID- 8998346
TI  - [Antigen showing alternative to alpha-fetoprotein expression in rat hepatomas].

PMID- 8998348
TI  - [Expression of Fas/APO-1/CD95 antigen mediating the apoptosis in human leukemic
      cells].

PMID- 8998349
TI  - [Possible mechanisms of allergic reactions of skeletal muscle].

PMID- 8998350
TI  - [Neoadjuvant chemotherapy and cyclo-oxygenase pathway of arachidonic acid
      metabolism in osteogenic sarcoma].

PMID- 8998351
TI  - [Sex-dependent characteristics of vagal regulation of of corticosterone secretion
      in rats].

PMID- 8998352
TI  - [Proliferative effect of prolactin and growth hormone from human serum in
      cultured rat lymphoma Nb2 cells].

PMID- 8998353
TI  - [Changes in blood viscosity in patients with infectious-allergic form of
      bronchial asthma undergoing photohemotherapy with low-energy helium-neon laser].

PMID- 8998354
TI  - [Characteristics of hypophyseal-adrenal and sympathetic-adrenal systems in
      patients with complicated spinal trauma].

PMID- 8998355
TI  - [Morphofunctional state of rat ovaries after administration of platidiam].

PMID- 8998356
TI  - [The level of thymic factor, thymalin, in human and murine skin epithelium, and
      its changes in ontogenesis].

PMID- 8998357
TI  - [Morphofunctional characteristics of alveolar macrophages in shock traumas].

PMID- 8998358
TI  - [Effect of hypoxia on morphofunctional parameters of astrocytes in a monolayer
      culture].

PMID- 8998359
TI  - [Recombinations of neocortex ultrastructure in hibernating animals during
      adaptation to hypothermia].

PMID- 8998360
TI  - [Peritoneal adhesions and possible mechanisms of their formation].

PMID- 8998361
TI  - [A method of evaluation of biomechanical characteristics of coronary vessels from
      contraction to contraction].

PMID- 8998362
TI  - [Living tissue surrogate for testing of surgical lasers].

PMID- 8998363
TI  - Expression systems.

PMID- 8998364
TI  - Great particles [32P]chromic phosphate for treatment of solid tumors.
AB  - With the purpose of studying the effectivity of an intratumoral single dose of
      chromic [32P] phosphate with great particles for the treatment of solid tumors,
      studies of bioelimination, biodistribution and therapeutic action were carried
      out. Only for comparative purposes, similar studies were undertaken using a
      solution of sodium -32P- orthophosphate-gelatine. The results show that when
      sodium [32P] orthophosphate-gelatine is used, the percentage of total elimination
      is (85.90 +/- 8.70)% with a higher percentage in urine (64.50 +/- 13.70)% than in
      faeces (21.40 +/- 4.50)%. In biodistribution studies, the greater percentage is
      found in bone (15.54 +/- 2.21)% while only a (2.51 +/- 0.39)% remains in the
      tumor. When great particles chromic [32P]phosphate was intratumorally injected,
      we determined that the total elimination is equal (36.28 +/- 6.27)%, finding a
      higher amount in faeces (29.44 +/- 5.26)% than in urine (6.84 +/- 2.21)%.
      Biodistribution studies demonstrated that (49.82 +/- 5.41)% remains in the tumor
      and (9.63 +/- 4.89)% of the injected activity is found in the liver. On the other
      hand, when therapeutic action was evaluated, we observed that the percentage of
      tumor regression (P.T.R.) is 52.0% for the tumors injected with chromic
      [32P]phosphate and 0.0% for those injected with sodium [32P]orthophosphate
      gelatine. These results show that the great particles colloid of chromic
      [32P]phosphate is not safe enough for the treatment of solid tumors, since it is
      mobilized from the injection point, delivering a high dose to the whole organism.

PMID- 8998365
TI  - Reduced renal sodium excretion in Walker-256 tumor-bearing rats.
AB  - Subcutaneous inoculation of Walker-256 tumor is followed by an asymptomatic
      period which is widely variable in duration, after which, paraneoplastic effects
      appear suddenly in the form of progressive and rapidly changing homeostatic
      alterations. Multifocal inoculation of tumor cells in each animal, was carried
      out with data averaging in each (sub-clinical [SubC], moderate [mCP] and grave
      [gCP] clinical phases and compared to foodrestricted (FR) rats. Results showed a
      significant and early decrease in urinary sodium excretion during mCP when
      compared to SubC and FR. The renal sites involved were studied in awake
      unrestrained animals by measure of sodium, creatinine and lithium clearance.
      Results indicated an initial increase of both absolute proximal (mCP: 21.4 +/-
      1.7 vs FR: 16.0 +/- 1.1 mmol@min/100 g.b.w., p < 0.05) and postproximal (mCP:
      11.1 +/- 0.4 vs FR: 6.6 +/- 0.4 mmol/min/100 g b.w., p < 0.001) Na+ reabsorption,
      which were partially compensated by a rise in glomerular filtration rate (mCP:
      213 +/- 11.4 vs FR: 162+ 10.2pl/min/100 g b.w., p < 0.01) and by fell of
      fractional proximal Na+ reabsorption (mCP: 62.8 +/- 2.2 vs FR: 70.1 +/- 1.7%, p <
      0.05), despite this a significant Na+ and fluid retention was observed.
      Additionally, this study shows that terminal phase of the illness (gCP)
      culminated with a marked decrease in the creatinine clearance suggesting a
      significant fall of the renal function.

PMID- 8998366
TI  - [Anticholinergic action of clonidine on cardiovascular effects of the central
      cholinergic estimulation].
AB  - A study was made relating the anticholinergic action of alpha 2-adrenoceptor
      agonist clonidine on the cardiovascular responses to i.c.v. injection of
      neostigmine, a quaternary anticholinesterase, in conscious rats. The cholinergic
      agent neostigmine (0.1-1 microgram i.c.v.) induced a dose-dependent pressor and
      bradycardic responses in the rats. Clonidine (10 micrograms.kg-1 i.v.), given 30
      min previous the anticholinesterase, failed to modify the pressor effect of
      neostigmine (0.1-1 microgram i.c.v.) but prevented the bradycardia. On the other
      side, the i.c.v. administration of clonidine (3 micrograms), given 15 min before
      neostigmine, only prevented the bradycardic effect of neostigmine (0.3 microgram
      i.c.v.) but not the central pressor action of this drug. The results support the
      idea that clonidine has an anticholinergic action in the rat. However, prevention
      by clonidine of central cholinergic bradycardia suggests different cholinergic
      adrenergic interaction on the cardiovascular responses elicited by central
      administration of cholinergic agents.

PMID- 8998367
TI  - Kinetics of translation and glycosylation of pituitary glycoproteins.
AB  - The present study determines the basal kinetics of synthesis of translation (by
      [14C] leucine incorporation, [14C]leu-PROT] and of proximal (by [3H]mannose
      incorporation, [3H]man-PROT) and distal (by [3H]galactose incorporation, [3H]gal
      PROT) glycosylation of total adenohypophyseal glycoproteins, by rat pituitary
      cells in primary culture. In order to obtain more information regarding the role
      of both steps of glycosylation on the secretory process, the effects of
      cycloheximide (CH; translation inhibitor) and tunicamycin (TM;glycosylation
      inhibitor) on the kinetics of synthesis and release of pituitary glycoproteins
      were also studied. Cells were incubated in medium containing [14C]leu plus
      [3H]man or [14C]leu plus [3H]gal, for various time-intervals (from 0.5 to 5 h) in
      the absence (control) or presence of different doses of CH (1.0; 4.0 or 16.0
      micrograms/ml) or TM (0.5; 1.0 or 2.0 micrograms/ml). The kinetics of synthesis
      (slope = 3488) and release (slope = 622) of [14C]le-PROT were higher than those
      of the sugar precursors (slopes: [3H]man-PROT = 1751 and 526; [3H]gal-PROT = 1231
      and 506). Leucine or mannose-labeled protein was barely detectable in the medium
      after 2 h incubation, whereas galactose-labeled protein had already been released
      into the incubation medium by 30 min. Cycloheximide induced translation blockage
      and, concomitantly, produced a marked inhibition of [3H]man incorporation. On the
      other hand, TM inhibited the kinetics of synthesis and release of [3H]man-PROT
      without affecting those of [14C]leu-PROT. The kinetics of synthesis and release
      of [3H]gal-PROT, although diminished, maintained linearity and increased in
      function of time, even in the presence of the antibiotics. Thus, the present
      results on glycoproteins from the pituitary gland are consistent with the
      previous conclusion for other mammalian glycoproteins that carbohydrate
      attachment occurs in several steps to molecules destined to be secreted. Addition
      of mannose (proximal glycosylation) is a co-translational event and that of
      galactose (distal glycosylation) is post-translational and can be designated as
      final stages in carbohydrate assembly, occurring close to the time of release.
      Furthermore, it has been demonstrated that the absence of the carbohydrate side
      chains of the pituitary glycoprotein does not prevent the intracellular transport
      of the protein and its export from the cell.

PMID- 8998368
TI  - Cardiac beta receptors' density or affinity modified by different Trypanosoma
      cruzi amount.
AB  - Chagas' disease presents complex physiopathogenic mechanism, many of them poorly
      understood, that in our country generally produce cardiac lesions. The acute
      phase related with the presence of the parasite is usually asymptomatic. This
      report studies if the amount of T. cruzi that induced acute infection could
      modify the myocardiopathy evolution. Previous works have shown that Albino Swiss
      mice inoculated with 45 tripomastigotes (AcL) presented alterations in the
      cardiac pharmacological response to adrenergic agonist and antagonist studied at
      30 days post-infection (p.i). Mice inoculated with 7 x 10(4) parasites/animal
      showed similar behaviour at 7 days p.i. We studied the involvement of the
      affinity and density of cardiac beta receptors in both acute groups by binding
      with 3H/DHA. The AcH group presented less cardiac beta receptors number (p <
      0.001), but their affinity was conserved. The AcL model presented significantly
      less affinity (p < 0.01) but density was not different from non infected animals.
      beta receptors' affinity of both infected groups were similar, but AcH density
      was significantly diminished when compared with AcL. These studies demonstrates
      that the amount of T. cruzi received by the host determines and acelerates the
      evolution of the chagasic myocardiopathy.

PMID- 8998369
TI  - Non enzymatic liver cells isolation: citrate-perchlorate technique.
AB  - In the present study we describe a non-enzymatic technique for the isolation of
      rat hepatocytes by perfusion of liver through portal vein. The perfusion media
      consist of 1 mM sodium perchlorate, 5 mM sodium citrate, 10 mM glucose, 129 mM
      NaCl and 0.1% bovine-serum albumin at pH 7.4. After purification through
      diatrizoate gradient, electron microscopical studies revealed that most of
      purified hepatocytes were well preserved and presented a normal ultrastructure,
      thus correlating with previous biochemical results. The present method enables
      the recovery of metabolically and morphologically normal hepatocytes.

PMID- 8998370
TI  - Effect of ethanol on glycerolipid and fatty acid metabolism in Hep G2 human
      hepatoma cells.
AB  - It is well-known that ethanol alters fatty acid and glycerolipid metabolism in
      liver, but most of the studies have been developed on rats, so little is known
      about the corresponding effects on human liver. We have chosen the Hep G2 human
      hepatoma cell line, which appears to be an excellent in vitro model system. Cells
      were incubated in ethanol containing medium (0-400 mM) for 48 h. Incorporation
      and metabolism of radioactive substrates (14C(U) glycerol,[1-14C] palmitic acid
      and [1-14C] eicosatrienoic acid (n-6) were analyzed in cellular and conditioned
      medium lipids. Cellular growth rate and lipid composition of control and ethanol
      treated cells were also studied. The results showed that ethanol inhibited
      logarithmic cellular growth rate in a concentration dependent manner, without
      affecting viability. Ethanol (400 mM) did not modify cellular major lipid
      composition except for an increase of cholesteryl esters, but produced a decrease
      in the proportions of myristic, palmitic and palmitoleic acids. Ethanol enhanced
      the incorporation of radioactive fatty acids into cellular glycerolipids but did
      not alter the rate of incorporation of 14C(U) glycerol. This was attributed to an
      isotopic solution of the radioactive glycerol as a result of increased alpha
      glycerophosphate biosynthesis. Incorporation of radioactive fatty acids and
      glycerol into conditioned medium glycerolipids were increased in cells incubated
      in presence of ethanol. The increased incorporation of 14C glycerol into
      conditioned medium together with a simultaneous diminution in labeling cellular
      glycerides suggest that there would be a stimulation of the export of these lipid
      classes to conditioned medium. Conversion of [1-14C] palmitic to oleic acid and
      eicosatrienoic to arachidonic acid were inhibited in 400 mM ethanol treated cells
      suggesting an inhibition of delta 9 and delta 5 desaturase activity.

PMID- 8998371
TI  - Precancerous pathology evoked by hexachlorobenzene treatment.
AB  - The porphyrinogenic and carcinogenic ability of hexachlorobenzene (HCB) was
      assayed in male and female gold hamsters, and histological examinations of tissue
      alterations were performed. So it was studied, in liver: a) porphyrin content
      which was significantly increased at five months of HCB treatment, specially in
      males, and the pattern of accumulated porphyrins which was altered independent of
      the sex, b) haem pathway enzymes:delta aminolaevulinic acid synthase,
      ferrochelatase and porphyrinogen carboxylyase (PCL); among which only PCL
      appeared to be altered just at ten months of HCB feeding. While thyroid gland and
      kidney remained unaltered along the treatment time, liver and spleen exhibited a
      noticeable size variation and morphological alterations. In fact the spleen in
      treated animals was hypotrophic showing a red pulp less developed with respect to
      the Malpighian corpuscles and many macrophages with iron deposits. Respect to the
      liver, enlargement in size of hepatocytes, high content of iron deposits, no PAS
      positive structures in the cytoplasm, several small lipid droplets,
      microsteatosis although no cytonecrosis, polymorphic nuclei, and proliferations
      of nucleoli were observed. Therefore HCB is able to cause precancerous pathology
      and to induce porphyria in hamsters, but not hyperthyroidism, upon this
      experimental conditions. By the way, males were found to be a good experimental
      model, better than females, to study the earliest relations between porphyria and
      cancer.

PMID- 8998372
TI  - New methodology for pancreatic scintiscanning imaging using 125I-L-3 Iodo-alpha
      Methyl Tyrosine.
AB  - The difficulty of a reliable diagnosis of pancreatic diseases by scintiscanning,
      is mainly derived from the lack of adequate radiopharmaceuticals. With this
      purpose 125I-L-3 Iodo-a-Methyl Tyrosine (125I-IMT) has been studied, which has
      also been used for the diagnosis of different kind of brain tumors. The purpose
      of this work is the development of a quick and easy method for the synthesis and
      purification of the 125I-IMT in order to be used in a Nuclear Medicine Service.
      The L-alpha-Methyl Tyrosine was labeled with 125I using I-/I03 and afterwards
      purified by an anionic exchange resin. The labeling yield obtained was (96.0 +/-
      0.5)% when the incubation time was 15 minutes. No significant statistical
      differences were observed when the incubation time was extended to 1 hour.
      Biodistribution studies in mice show that the percentage of activity
      concentration in pancreas is (34.24 +/- 14.03)% at 15 minutes post injection,
      remaining constant for 30 minutes. The pancreas/liver ratio 15 minutes after the
      injection of the labeled product was (12.22 +/- 3.59) and it remained constant
      for 45 minutes more. These results show that 125I-IMT can be used as a diagnostic
      agent for pancreatic diseases. Since 123I was not available at the moment, this
      new methodology was developed with 125I.

PMID- 8998373
TI  - Effect of Equine Hypothalamic Extract on hormone secretion by the adenohypophysis
      of rats.
AB  - The effect of Equine Hypothalamic Extract (EHE) on pituitary weight and secretion
      of TSH, FSH-LH and ACTH was studied in the rat. The pituitary response to EHE was
      assessed by measuring 131I uptake by the thyroid and by weight changes of the
      pituitary glands, thyroids, adrenals, ovaries and uteri. 131I uptake of the
      thyroid and weights of the pituitary, thyroid, adrenal and uterus increased in
      the treated rats, whereas ovarian weights were similar to control groups. These
      findings indicate that the EHE containes hypophysiotropic peptides which can
      stimulate the secretion of pituitary hormones in the rat.

PMID- 8998374
TI  - [Effects of Bothrops alternatus venom of Argentina on muscle and different organs
      in mices].
AB  - Bothrops alternatus venom was inoculated in gastrocnemius muscle of mice between
      18 and 20g. The dose was 50 micrograms in 0.1 ml in ClNa 0.85% solution. Groups
      of 5 animals were sacrified between 3, 6 and 12 hours after inoculation.
      Hystopathology was performed with muscle and different organs fixed with Bouin.
      The venom reproduced a local inflammatory reaction. Histopathology observations
      of muscle revealed myolytic and coagulative necrosis. There and six hours after
      inoculation, hepatocellular degeneration and tumefaction in area of central veins
      was observed. In kidneys there were cortical congestion and hydropic tumefaction
      of proximal and distal tubules. There were no anormality in heart, lung and
      brain.

PMID- 8998375
TI  - Selegiline in treatment of behavioral and cognitive symptoms of Alzheimer
      disease.
AB  - OBJECTIVE: To evaluate the effects of selegiline on behavioral and cognitive
      symptoms of patients with Alzheimer disease. DATA SOURCES: An English-language
      MEDLINE search (1982-1995) was used to identify the review articles and human
      clinical trials discussed in this article. STUDY SELECTION: Double- and single
      blind and open-label trials were reviewed. Studies were also reviewed if
      selegiline was evaluated comparatively with other agents. Review articles were
      used for background information. DATA EXTRACTION: Data were evaluated from human
      studies. Studies were critiqued on the basis of design, methodology, duration,
      sample size, and the degree to which neuropsychological tests used in each study
      were compared. DATA SYNTHESIS: Selegiline is a selective, irreversible inhibitor
      of monoamine oxidase type B. Eight of 11 controlled trials showed selegiline had
      a positive effect on cognition (e.g., word fluency, delayed recall, total
      recall). Two of 5 controlled trials evaluating selegiline's effect on behavior
      (e.g., anxiety, tension, excitement, depression) showed a positive effect.
      CONCLUSIONS: The role of selegiline remains to be determined by large well
      controlled long-term clinical trials. Selegiline may be a useful agent in
      managing behavioral and cognitive symptomatology associated with Alzheimer
      disease. Given that the management of Alzheimer disease is symptomatic and no
      standard treatment exists, selegiline should be considered among the various
      options.

PMID- 8998376
TI  - Our first supplement.

PMID- 8998377
TI  - Afferent impulse discharges from glucoreceptors in the liver of the guinea pig.

PMID- 8998378
TI  - Diet and malignancy: five decades of rediscovery.

PMID- 8998379
TI  - Thalidomide and isotretinoin--why treat them differently?

PMID- 8998380
TI  - Exposure to organic solvents during pregnancy and oral clefts: a case-control
      study.
AB  - Prior studies on the relationship between maternal exposure to organic solvents
      in relation to oral clefts have been inconsistent. We re-examined this
      relationship in a case-control study conducted in the Rhone-Alpes region of
      France during the years 1985 to 1989. For each case, we selected two controls
      without congenital anomalies in the same delivery unit born during the same
      month. We interviewed each mother within the first five days after delivery about
      previous reproductive history and exposures during the first two months after
      conception. If the mother had an occupational activity at that time, we asked her
      occupational physician to confirm the exposures. We compared maternal exposure to
      any organic solvent between 200 infants with cleft lip and/or cleft palate and
      400 controls and the estimated odds ratio was 1.62 (95% CI 1.04-2.52). Then we
      compared exposures to nine subgroups of solvents. Only the ratio associated with
      halogenated aliphatic solvents (4.40, 95% CI 1.41-16.15) was significantly
      different from unity. Control of potential confounders-sex of child, family
      history, maternal epilepsy-did not alter this odds ratio estimate.

PMID- 8998381
TI  - Congener-specific effects of PCBs on contractions of pregnant rat uteri.
AB  - Both increased and decreased gestation lengths have been reported following
      exposures to polychlorinated biphenyl (PCB) mixtures and congeners. Because
      oscillatory uterine contractions are essential for parturition, we hypothesized
      that the disparate findings on gestation length may be the result of distinct PCB
      congener-specific actions on oscillatory uterine contractions. This study
      examined the acute effects of PCB congeners on isometric contractions of isolated
      pregnant uteri and the structure-activity relationship for individual congeners.
      After cumulative exposure to individual PCB congeners (0.5 microM to 150 microM),
      oscillatory contractions were: 1) not altered by 2,4,5,2',4',5'
      hexachlorobiphenyl, 3,4,5,3',4'-pentachlorobiphenyl, or 3,4,3',4'
      tetrachlorobiphenyl; 2) significantly inhibited by 4-hydroxy-2',4',6'
      trichlorobiphenyl; and 3) markedly increased by 2,4,6-trichlorobiphenyl and
      2,4,2',4'-tetrachlorobiphenyl, when compared to solvent controls. The uteri were
      more sensitive to PCB congeners with ortho-substituted light chlorination than
      those highly chlorinated, or those interacting with the Ah-receptor.

PMID- 8998382
TI  - Twelve-month evaluation of rhesus monkey dams and infants after relaxin (hRlx-2)
      infusion in late pregnancy.
AB  - Pregnant rhesus monkeys received daily i.v. infusions of chemically synthesized
      human relaxin (hRlx-2) (0.1 mg/kg/day N = 6, 2.0 mg/kg/day N = 6, vehicle control
      N = 7) from the onset of cervical softening to delivery (0 to 14 infusions) to
      simulate potential therapeutic use of this agent for cervical ripening.
      Reproductive fitness of dams was evaluated during the next breeding season, and
      infants were studied through 12 months of age. Birth weight and size, neonatal
      heart rate and body temperature and neurobehavioral status were not influenced by
      intrauterine relaxin exposure. Neonatal muscle tone was greater and
      responsiveness was lower in the hRlx-2 treated infants than in controls. No group
      differences were seen in infant postnatal growth, maturation or incidence of
      health problems. Maternal endpoints including uterine involution, resumption of
      menses, conception rate, and pregnancy outcome were similar across groups.
      Systemic exposure of rhesus monkeys to relatively high levels of hRlx-2 in late
      pregnancy did not have apparent long term effects for the measures evaluated
      under conditions of the experiment. Conclusions concerning adverse effects are
      limited by the small sample size.

PMID- 8998383
TI  - Reproductive risks of binge drinking during pregnancy.

PMID- 8998384
TI  - Cocaine selectively alters neurotransmitter receptor mRNAs in mouse embryos.
AB  - Alterations in gene expression due to in utero cocaine exposure may adversely
      affect nervous system development. The present study examined whether or not
      cocaine administration to pregnant mice alters embryonic mRNA levels for several
      developmentally-regulated genes. Antisense RNA amplification was performed using
      RNA from LM/Bc embryos at gestational days 9.5 and 10.5 after three days of
      cocaine treatment. This technique highlights simultaneous changes that occur in
      the expression of many genes after a teratogenic insult. Significant changes
      occurred in the expression pattern on only four genes from a total of 42
      candidate cDNAs. These included increases in the relative levels of the alpha and
      beta 1 subunits of the GABAA receptor without concurrent changes in the non-NMDA
      glutamate receptor subunits. The results support the hypothesis that in utero
      cocaine exposure leads to specific changes in gene expression that may ultimately
      contribute to developmental abnormalities.

PMID- 8998385
TI  - Prenatal toxicity studies in rats and rabbits with the calcium channel blocker
      diproteverine.
AB  - In prenatal toxicity studies, diproteverine, a calcium channel blocker with
      demonstrated antianginal properties, produced an unusual pattern of digital,
      heart, tail, and vertebral defects in rat fetuses from mothers treated during the
      major period of organogenesis, but only a very low incidence of heart
      abnormalities was seen in the rabbit. Heart changes were rarely seen in
      association with digital defects. The findings were consistent with those seen
      with other calcium channel blockers and add weight to the suggestion of
      Danielsson and colleagues (5) that digital malformations are a class effect for
      this type of compound, the effects being related to reduced uteroplacental blood
      flow. In addition, it is proposed that cardiovascular malformations are also a
      class response with calcium channel blockers. The distribution of fetal death and
      hemorrhages and the varying association between cardiovascular, digital, and tail
      abnormalities seen in the rat with increasing doses of diproteverine fits the
      pattern of changes reported following hypoxia in the chick embryo. Reduced
      uteroplacental blood flow with resultant embryonic hypoxia secondary to
      pharmacologic action is considered a probable mechanism of action for the
      induction of abnormalities produced by calcium channel blockers.

PMID- 8998387
TI  - Permanent testicular damage induced in rats by a single dose of tunicamycin.
AB  - Tunicamycin administered as a single subcutaneous dose of 200 micrograms/kg
      caused permanent destruction of seminiferous tubules in adult male rats. The
      fertility of females was unimpaired by doses of up to 450 micrograms/kg.
      Degenerative changes in seminiferous tubule epithelium commenced 3 to 5 days
      after injection and by day 19 affected 95% of tubule profiles in sections. In 95%
      of tubules only Sertoli cells survived to day 56. Tubules without any surviving
      cells were present from day 19 and slowly increased in number, a variable
      proportion becoming mineralised. No regeneration occurred within one year. Leydig
      cells became more prominent because of the atrophy of seminiferous tubules, but
      their total mass did not differ significantly from that of control rats, nor did
      the plasma concentration of testosterone. Changes in tissues other than the tests
      were transient. The testicular damage seems to have resulted from localised
      ischaemia caused by tunicamycin-induced vasoconstriction.

PMID- 8998386
TI  - DNA strand breaks in testicular cells from humans and rats following in vitro
      exposure to 1,2-dibromo-3-chloropropane (DBCP).
AB  - Preparations of testicular cells from human organ transplant donors and from
      Wistar rats were compared with respect to their composition of the different
      testicular cell types, their ability to metabolize 1,2-dibromo-3-chloropropane
      (DBCP), and their relative sensitivity to induction of DNA single strand breaks
      and alkali labile sites (ssDNA breaks) after treatment with DBCP, 4
      nitroquinoline N-oxide (4-NQO), and X rays. Flow cytometric and microscopic
      analysis demonstrated that the interindividual variation in the composition of
      testicular cell types was considerably greater in the human tissue than in that
      from rats. The in vitro metabolic activation of DBCP (50 to 250 microM), measured
      as radiolabel covalently bound to macromolecules, was three-fold faster in rat
      testicular cells compared to human testicular cells. X rays (1 to 10 Gy) and 4
      NQO (0.5 to 2.5 microM) induced ssDNA breaks to a similar extent in both human
      and rat testicular cells as measured by single cell get electrophoresis (SCGE)
      and alkaline filter elution. In contrast, 1,2-dibromo-3-chloropropane (DBCP) (3
      to 300 microM) caused no significant DNA damage in human testicular cells,
      whereas in rats there was a clear concentration-dependent increase in ssDNA
      breaks. The data show that, compared to rats, testicular cells from humans are
      less efficient in activating DBCP to metabolites binding covalently to
      macromolecules. However, from the rate of covalent binding observed one would
      expect a significant degree of DBCP-induced ssDNA breaks in the human testicular
      cells. The low level of DBCP-induced ssDNA breaks in human testicular cells could
      indicate that different reactive DBCP metabolites are involved in binding to
      cellular macromolecules compared to DNA damage, or that different rates of DNA
      repair exist in human and rat testicular cells.

PMID- 8998388
TI  - Potentiation of testicular cytotoxicity by the alkyltransferase inhibitor O6
      benzylguanine and the 5-fluorouracil/N-(2-chloroethyl)-N-nitrosourea molecular
      combination, B.4152.
AB  - Alkylating agents are a group of compounds that have a cytotoxic effect due to
      their ability to form adducts with DNA. Cells possess the ability to repair this
      damage via an enzyme, O6-alkylguanine-DNA alkyltransferase (AGT). To study the
      effect of inhibiting this repair mechanism upon testicular cytotoxicity in BALB/c
      mice, the AGT inhibitor O6 benzylguanine (O6BG) was used in conjunction with the
      potential anticancer drug B.4152. Paraffin sections were stained and examined
      using Chalkley scoring to identify the cells affected by the treatment. Using
      B.4152 alone the maximal effect upon the spermatogenic tissue was found to be
      after 32 days. The damage found was minor, with the spermatocytes and spermatids
      most affected. Using this time point it was found that the combined treatment
      produced widespread damage, with significant depletion of the majority of
      spermatogenic cell types. These results therefore, indicate that differentiating
      spermatogenic cells are normally protected from B.4152 induced damage by AGT,
      depletion of which significantly potentiates B.4152 toxicity.

PMID- 8998390
TI  - Nasopancreatic drainage: a novel approach for treating internal pancreatic
      fistulas and pseudocysts.
AB  - Internal pancreatic fistulas are rare but debilitating complications of chronic
      pancreatitis. Fistulous tracts from the pancreatic duct to the peritoneal or
      pleural cavities have been treated by medical therapy and surgical management,
      with success rates of 41% and 89%, respectively. Endoscopic stent placement for
      internal and external pancreatic fistulas has also been shown effective. We
      report on three patients with histories of chronic alcohol abuse and
      pancreatitis. Two patients presented with dyspnea and pleuritic chest pain.
      Imaging studies revealed pleural effusions, and endoscopic retrograde
      cholangiopancreatography (ERCP) demonstrated a patent fistulous tract from the
      pancreatic duct to the pleural cavity in each patient. Chemical analysis of the
      pleural fluid indicated pancreatic origin. The third patient, who had left-upper
      quadrant abdominal pain and a small pleural effusion, had a large
      noncommunicating pseudocyst adjacent to the stomach. Nasopancreatic drains, along
      with chest tube drainage, were placed in the patients with pancreatic pleural
      fistulas. The patient with the pseudocyst received nasocystic drainage via the
      stomach. Drainage was measured until closure of the fistulas or cyst.
      Additionally, simply by injecting contrast medium, we were able to monitor the
      closure of fistulas without ERCP. The fistulas closed within 7 days, and the
      pseudocyst resolved within 14 days. Following discharge, all three patients were
      pain free, without evidence of recurrent fistulas or pseudocyst. In conclusion,
      the use of nasopancreatic/cyst drainage is an effective and convenient way to
      treat internal, communicating collections and pseudocysts of pancreatic origin.
      Furthermore, this method provides a simple means of assessing closure of fistulas
      and pseudocysts.

PMID- 8998389
TI  - Urinary creatine as a potential marker of testicular damage: effect of vasectomy.
AB  - The concentrations of creatine in the rat testis are high compared to all other
      tissues except muscle. The total creatine content of the testis is also
      considerably greater than all organs examined except muscle. Vasectomised male
      rats were given 2-methoxyethanol or cadmium chloride at doses that caused
      testicular damage. In the vasectomised rats, testicular damage still resulted in
      significant creatinuria. This indicates the creatine reaches the urine at least
      partly via the blood stream and not via the vas deferens.

PMID- 8998392
TI  - Photosensitivity and antinuclear antibodies in black patients with systemic lupus
      erythematosus.
AB  - Black patients with systemic lupus erythematosus (SLE) have a lower prevalence of
      photosensitivity rashes than white patients. The reasons for this are unknown,
      but some studies suggest a correlation between the presence of antinuclear
      antibodies and protection from photosensitivity. In our study, we determined
      serum antinuclear-antibody profiles, including anti-dsDNA, anti-Sm, anti-RNP,
      anti-Ro/SS-A, and anti-La/SS-B antibodies, in 91 black Jamaican patients with
      SLE. All 91 serum samples from SLE patients (100%) were positive in the
      fluorescent antinuclear-antibody test. Using the crithidia luciliae
      immunofluorescence test, anti-dsDNA was found in 27.5% of the samples. By a
      double immunodiffusion method, anti-Sm antibodies were found in 15.4%, anti-RNP
      in 18.7%, anti-Ro/SS-A in 9.9%, and anti-La/SS-B in 11.0%. However, no
      statistically significant differences were observed in the seroprevalence of
      these antinuclear antibodies when sera from patients of the following groups were
      compared: only photosensitivity rashes (n = 17), photosensitivity and other
      rashes (n = 23), other rashes without photosensitivity (n = 27), and patients
      with no skin rash of any type (n = 24). These results suggest that
      photosensitivity in black Jamaican patients with SLE is not associated with
      antinuclear-antibody specificity.

PMID- 8998391
TI  - Modulation of central nervous system metabolism by macromolecules: effects of
      albumin and histones on glucose oxidation by synaptosomes.
AB  - Since increasing evidence suggests that several proteins play a significant role
      in the regulation of glucose oxidation in the central nervous system, a series of
      experiments was designed to determine the specific proteins involved and to
      delineate their possible mode of action. In these studies, the rate of substrate
      oxidation by isolated synaptosomes in vitro was determined by measuring the
      production of [14C]carbon dioxide from labeled compounds in the presence and
      absence of the added protein. In the initial experiments, an examination of a
      broad selection of pure proteins revealed that only albumin (bovine serum albumin
      [BSA]) or histones (at concentrations of 100 micrograms/mL or less) exhibited an
      inhibitory effect of greater than 60% on the rate of glucose oxidation.
      Furthermore, isolated cell fractions P1 (nuclei and cellular debris), P2
      (mitochondria, synaptosomes, and myelin), and other membrane proteins had little
      or no effect on the rate of [14C]carbon dioxide production from [6(14)C]glucose.
      When either BSA or histones were treated with trypsin, the inhibitory effects
      were eliminated. To determine whether these effects were related to changes in
      substrate transport, we measured the rate of glucose uptake by synaptosomes using
      [6(14)C]glucose, [1,2-3H]2-deoxyglucose, and [3H]3-O-methylglucose in the
      presence of 5% serum protein. These experiments revealed that the rate of glucose
      transport was not affected by serum proteins. Collectively, these results
      indicate that albumin and histones attenuate the rate of glucose oxidation by
      synaptosomes. The results also support the conclusion that the intact protein
      molecule is required for this inhibition, since treatment with trypsin abolished
      this effect. It can also be concluded that this effect is not at the site of
      transport and that the protein(s) are acting either directly at intercellular
      site(s) or indirectly via specific messengers.

PMID- 8998393
TI  - Whither academic health centers? A commentary.
AB  - Academic health centers (AHCs) currently face the greatest challenge of their
      entire existence. Managed care, increased competition for research funding, and
      inefficiency all contribute to the present vulnerability of AHCs in the cost
      competitiveness of today's health care marketplace. The increased reliance of
      medical schools on clinical income to subsidize undergraduate and graduate
      education and biomedical research now jeopardizes the success of their missions,
      since clinical income is declining. While AHCs must make significant changes to
      adapt to the new environment, left on their own in the marketplace, many will not
      survive. Additionally, the biomedical research advances and high technology
      medical care that we have come to expect in this country will also likely suffer.
      A national approach designed to preserve responsive AHCs is needed.

PMID- 8998394
TI  - Weight gain induced by clozapine.
AB  - Patients were investigated to gain more insight into the incidence and time
      course of clozapine induced weight gain (n = 81) and to compare weight gain in
      patients treated with clozapine (n = 31) with that of patients treated with
      standard antipsychotics (haloperidol, n = 11). 35.7% of the patients treated with
      clozapine gained weight according to our definition. If patients gained weight on
      clozapine this side effect was apparent within the first 12 weeks of treatment.
      Deviation from normal body weight at the beginning of treatment showed a
      significant influence on weight gain. Sex, severity of illness, comedication,
      mean clozapine dose and degree of improvement did not show an influence on this
      side effect. Weight increase was significantly higher in patients treated with
      clozapine than in patients treated with haloperidol.

PMID- 8998395
TI  - A double-blind study comparing the efficacy and tolerability of mirtazapine and
      doxepin in patients with major depression.
AB  - One hundred and sixty-three patients with major depression were randomly assigned
      to treatment with mirtazapine or doxepin for 6 weeks in a double-blind clinical
      trial. Initially, patients received mirtazapine 20 mg/day or doxepin 75 mg/day;
      dosages were then titrated up to a maximum of 60 mg/day and 300 mg/day,
      respectively. Both drugs produced considerable improvement in depressive symptoms
      with no statistically significant differences between the two patient groups. In
      the mirtazapine group only two patients prematurely terminated the study due to
      adverse drug experiences, as compared to six in the doxepin-treated group.
      Moreover, doxepin-treated patients complained more frequently of dry mouth and
      movement disorders. In conclusion, mirtazapine is an effective treatment for
      major depression and appears to offer advantages in tolerability over doxepin.

PMID- 8998396
TI  - Impaired exploratory behaviour after DSP-4 treatment in rats: implications for
      the increased anxiety after noradrenergic denervation.
AB  - The effect of DSP-4, a neurotoxin selectively affecting the projections of the
      locus coeruleus, upon exploratory behaviour of rats was studied in a complex
      exploration test, including a choice between open and enclosed areas and both
      inquisitive and inspective exploration elements. One week after DSP-4 (50 mg/kg
      i.p.) administration, the neurotoxin-treated rats did not explore a novel open
      area to any extent on the first exposure to the apparatus; however, on the third
      day of testing, these animals began to explore the area and the novel objects.
      Diazepam (0.5 mg/kg) treatment did not change the behaviour of control rats, but
      significantly increased the exploratory activity of the DSP-4-treated animals. LY
      288513, a selective CCKB receptor antagonist (0.01 mg/kg), prevented the increase
      in exploratory activity in the DSP-4-treated rats, but increased the exploratory
      activity of controls on the third exposure to the test situation. The results of
      this investigation suggest that DSP-4 treatment reduces neotic behaviour by
      increasing neophobia rather than by decreasing exploratory drive. The divergence
      reported between the relative potencies of CCKB receptor antagonists in
      exploratory activity and other anxiety tests may in part be due to the effects of
      these drugs on exploratory drive.

PMID- 8998398
TI  - Adaptive changes in the proenkephalin and D2 dopamine receptor mRNA expression
      after chronic cocaine in the nucleus accumbens and striatum of the rat.
AB  - The effects of single and repeated cocaine administration on proenkephalin (PENK)
      and D2 dopamine receptor mRNA expression in the nucleus accumbens and striatum of
      the rat were studied. Acute cocaine administration increased PENK expression of
      mRNA in the striatum and decreased it in both those structures after 24 and 48 h.
      D2 receptor expression of mRNA fell after 3 h, returned to the control value
      after 24 h and rose after 48 h in both those brain regions following single
      cocaine injection. Repeated cocaine increased PENK expression of mRNA after 3 h,
      but after 24 and 48 h depletion of mRNA expression was observed. On the other
      hand, a decrease in the D2 expression of mRNA was found after 3 h in those
      structures, but no changes were found after 24 and 48 h following withdrawal. The
      obtained results suggest that in the nucleus accumbens and striatum there is an
      opposite regulation between PENK and D2 receptor gene expression a short time
      after single and chronic cocaine administration. Hence, these data provide
      further evidence for the significance of the PENK and dopamine systems in the
      neurochemical mechanism of cocaine.

PMID- 8998397
TI  - The effects of D-cycloserine and MK-801 on the performance of rats in two spatial
      learning and memory tasks.
AB  - The present study was undertaken to investigate the effects of modulation of the
      N-methyl-D-aspartate (NMDA) receptor on learning and memory. Thus, the
      performance of rats treated with D-cycloserine, a partial agonist at the glycine
      recognition site of the NMDA receptor complex, and MK-801, a noncompetitive NMDA
      receptor antagonist, either alone or concurrently were assessed in radial arm
      maze and water maze tasks. Administration of MK-801 (0.1 mg/kg, i.p.) impaired
      acquisition in the water maze (increased escape latency and distance) and working
      memory in the radial arm maze (increased re-entries) in rats. Moreover, in the
      radial arm maze, MK-801 disrupted locomotion (increased latencies and decreased
      arm entries per minute) and impaired the acquisition of reference memory
      (increased number of errors) performance of rats. D-Cycloserine (0.03, 0.3, 1.0,
      3.0, 10 mg/kg, i.p.) had no effects on acquisition or memory performance of
      control or MK-801-treated rats in either of these tasks. However, D-cycloserine
      (0.03, 0.3, 3.0 mg/kg) reversed the MK-801-induced disruption in locomotion.
      Furthermore, 3.0 mg/kg D-cycloserine increased behavioral activity and also
      decreased the time needed to complete the task in control animals. To conclude,
      our results suggest that the consequences of NMDA receptor modulation on learning
      and memory processes and sensorimotor functions may be functionally different or
      have distinct anatomical locations.

PMID- 8998399
TI  - The behavioral effects of habituation and challenge with apomorphine after 6-OHDA
      lesioning of the nucleus accumbens in rats.
AB  - In rats the function of the dopamine system in the nucleus accumbens was tested
      after 6-OHDA lesioning of this brain area and after ORG 2766 induced facilitation
      of recovery in 6-OHDA lesioned animals. A low dose of systemically administered
      apomorphine (50 micrograms/kg) decreased motility when sham operated rats were
      placed in a novel environment. A similar decrease was found in saline treated
      rats tested for the second time 1 day later. In thus habituated animals, the low
      dose of apomorphine did not induce hypomotility. Thus habituation and
      hypomotility after a low dose of apomorphine may be due to a similar mechanism,
      viz. diminished dopamine release. A higher dose of apomorphine (125
      micrograms/kg) increased motility, but only when the rats were habituated to the
      test environment. Animals with a bilateral 6-OHDA lesion of the nucleus accumbens
      showed hypomotility when tested for the first time 1 week after the lesion. The
      low and the higher dose of apomorphine elicited hypermotility in both
      nonhabituated and habituated lesioned rats. Their activity was higher than in
      sham operated animals, suggesting supersensitivity of postsynaptically located
      dopamine receptor systems in lesioned rats. Treatment with the ACTH(4-9) analog
      ORG 2766 during the first week after induction of the lesion counteracted the
      hypomotility of the lesioned rats. Furthermore ORG 2766 enhanced the
      supersensitivity as revealed by challenge with the low dose of apomorphine.

PMID- 8998400
TI  - Potential antidepressant effects of lemon odor in rats.
AB  - Antidepressant effects brought about by olfactory stimulation with various
      odorants were investigated with the forced swimming test, a reliable means for
      screening antidepressant effects. Lemon odor significantly reduced total
      immobility time and potentiated the imipramine-induced reduction of total
      immobility time in the test. This synergistic effect of lemon odor and imipramine
      was not due to lemon odor decreasing the metabolism of imipramine. Lemon odor
      decreased locomotor activity in the open field, suggesting its effects to differ
      from those of psychostimulants but to be similar to those of antidepressants. The
      effects of citral, which is one of the main components of lemon odor, were as
      strong as those of lemon odor. The remaining odorants tested in this study failed
      to have any effects on total immobility time in the forced swimming test or on
      locomotor activity in the open field.

PMID- 8998401
TI  - Sigma ligand S14905 and locomotor activity in mice.
AB  - The binding and locomotor profile of a new sigma ligand, S14905, (isobutyl-N-(1
      indan-2yl-piperid-4-yl)N-methyl carbamate, furamate) was studied. The binding
      data revealed that S14905 has a high affinity for sigma receptors and very low
      affinity for both dopamine D1 and D2 receptors. We have demonstrated that this
      sigma ligand prevents the locomotor stimulation induced by morphine (32 and 64
      mg/kg), cocaine (16 mg/kg), amphetamine (4 mg/kg) and adrafinil (32 mg/kg) at
      doses lower than those required to depress spontaneous locomotor activity. The
      antagonism observed in the present study seems to be more specific of morphine
      induced hyperlocomotion. The high affinity of this compound for sigma receptors
      makes it a good choice to study the role of this receptor in the CNS. In
      addition, S14905 does not directly block dopamine receptors but may modulate them
      in some manner, and would thus warrant further study as a potential atypical
      antipsychotic agent, and an antagonist for the hyperactivity induced by opiate
      drug.

PMID- 8998402
TI  - Neuropeptides and Alzheimer's disease.
AB  - Numerous neuropeptides have been isolated from the human brain and postulated as
      neurotransmitter candidates. Their biochemical characteristics and anatomical
      distribution have been elucidated in some detail, but their possible
      physiological and pathophysiological roles, as well as their utility as
      diagnostic markers in brain disorders, have been more difficult to establish. The
      concentrations of several neuropeptides have been measured in postmortem human
      brain studies and in cerebrospinal fluid (CSF) of patients with Alzheimer's
      disease. Here we critically review these findings with focus on: (1) the relation
      between brain tissue and CSF neuropeptide alterations; (2) the specificity of
      neuropeptide alterations in Alzheimer's disease in relation to other degenerative
      brain diseases; (3) possible functional implications.

PMID- 8998403
TI  - Effects of carbamazepine on membrane properties of rat sensory spinal ganglion
      cells in vitro.
AB  - The present study aimed to examine effects of the antiepileptic drug
      carbamazepine (CBZ) on membrane properties. Therefore, effects of CBZ on voltage
      dependent ion channels were investigated in rat sensory spinal ganglion cells in
      primary cultures. (i) Membrane potentials and action potentials were recorded by
      sharp microelectrodes: CBZ reduced neuronal excitability without changing the
      resting membrane potential, and suppressed tetrodotoxin (TTX)-resistant
      components of action potentials which were blocked by cobalt and hence were
      interpreted as Ca2+ spikes. The rising phase and peak amplitude of TTX-sensitive
      components of action potentials, however, were hardly altered. (ii) Voltage
      dependent inward and outward currents were elicited in the whole-cell
      configuration of the patch clamp technique. CBZ reduced (presumably L-type) Ca2+
      currents. In some cells Ca2+ currents partly recovered during washing with
      control saline. The effects on Na+ and K+ currents were not uniform and often
      insignificant. The present study indicates that CBZ has calcium-antagonistic
      properties.

PMID- 8998404
TI  - Non-amphetaminic mechanism of stimulant locomotor effect of modafinil in mice.
AB  - Previously established dose-response curves indicated that modafinil 20-40 mg/kg
      i.p. elicited in mice an obvious stimulation of locomotor activity roughly
      similar to that induced by (+)amphetamine 2-4 mg/kg. The effects of various
      agents modifying dopamine transmission were compared on the locomotor response to
      both drugs. The preferential D2 dopamine receptor antagonist haloperidol 37.5-150
      micrograms/kg i.p. suppressed the stimulant effect of (+)amphetamine in a dose
      dependent manner, but not that of modafinil. The D1 dopamine receptor antagonist
      SCH 23390 (7.5-30 micrograms/kg s.c.) reversed the (+)amphetamine but not the
      modafinil induced hyperactivity. The tyrosine hydroxylase inhibitor alpha-methyl
      para-tyrosine (200 mg/kg) suppressed the hyperactivity induced by 4 mg/kg
      dexamphetamine but not that induced by 20 mg/kg modafinil. Associating L-DOPA 150
      mg/kg and benserazide 37.5 mg/kg with (+)amphetamine 2 mg/kg resulted in
      stereotyped climbing behavior, that was not observed with modafinil 10-80 mg/kg.
      The profound akinesia induced by reserpine (4 mg/kg s.c.; 5 h before testing) was
      reversed by (+)amphetamine 2 mg/kg but not by modafinil 40 mg/kg. Finally, on
      synaptosomes prepared from mouse striata preloaded with [3H]dopamine, modafinil
      10(-5) M did not increase the spontaneous [3H]dopamine release whereas
      (+)amphetamine, at the same concentration, doubled it. From all these differences
      between the two drugs, it is concluded that the mechanism underlying the
      modafinil induced stimulant locomotor effect differs completely from that of
      (+)amphetamine.

PMID- 8998405
TI  - Endocrine and cardiovascular responses to a series of graded physical and
      psychological stress stimuli in healthy volunteers.
AB  - To investigate the endocrine and cardiovascular responses to a series of
      psychological and physical stress stimuli and to investigate the possibility of a
      stimulus intensity-response relation of endocrine and cardiovascular reactivity,
      18 healthy volunteers were exposed to psychological and physical stimuli of
      increasing intensity. Each volunteer participated in three experimental sessions
      on separate days. The sequence of the sessions was such that all volunteers first
      participated in a session in which they were not exposed to a stress stimulus,
      i.e. the control session. Then they were randomly assigned to enter two trial
      sessions in which they were consecutively exposed to a series of psychological
      stressors and a series of physical stressors. During each session blood pressure
      (BP) and heart rate (HR) were assessed and blood samples were taken, to determine
      cortisol and noradrenaline levels. During the physical stress session increments
      in systolic and diastolic blood pressure and noradrenaline were observed,
      proportional to the intensity of the stimuli. In contrast, during the
      psychological stress session pronounced increments in heart rate were observed,
      with maximum responses at the second and third stimuli. Diastolic blood pressure
      responses showed a similar pattern, whereas no changes in noradrenaline were
      observed. Plasma cortisol was not increased by the psychological stressor,
      whereas it was stimulated by the physical stressor but at the highest stimulus
      intensity only. Although the size of the study population precludes any firm
      conclusions, the results suggest that a stimulus intensity approach in human
      stress research is possible. Furthermore, the results also appear to indicate
      that the cardiovascular and pituitary-adrenal systems may display stress-specific
      responses.

PMID- 8998406
TI  - Behavioural responsiveness to picrotoxin and desipramine in adult rats prenatally
      exposed to different benzodiazepine receptor agonists.
AB  - The behavioural responsiveness to picrotoxin and desipramine was investigated in
      adult rats prenatally exposed to different benzodiazepine receptor agonists such
      as diazepam, alprazolam and zolpidem. Prenatal exposure to diazepam and
      alprazolam similarly potentiated the anti-immobility effect on the forced
      swimming test and the inhibitory effect on spontaneous motor activity of
      picrotoxin and desipramine and increased the seizure sensitivity to picrotoxin.
      Prenatal zolpidem seems to be ineffective. These data suggest that, despite the
      differences in their pharmacodynamic profile, prenatal exposure to diazepam and
      alprazolam, but not zolpidem, may have similar permanent consequences on the
      behavioural effects of drugs acting on the GABAA receptors.

PMID- 8998408
TI  - Clinical relevance of response and improvement in psychopharmacology: European
      College of Neuropsychopharmacology.
AB  - The use of responder categories may provide more clinically relevant information
      than mean differences on a severity scale but is not a definitive solution.
      Responder analysis is more useful in moderate illness than in mild or severe
      illness, depends on the timing of the analysis, and on the variance in the
      sample. Nevertheless, a statistically significant difference between drug and
      placebo treatment with respect to the percentage responders defined as a pre
      established degree of reduction on a pivotal severity scale may provide the most
      objective information about clinical relevance yet available. Using distributions
      of categories of response may be less restrictive and provide a better
      description of results but more data are needed before conclusions can be
      reached. Effect size is an attractive, apparently simple method of establishing
      clinical relevance but criteria are lacking on cutoffs for accepting an effect
      size as relevant. There is a need for more information on patient samples, a
      better exploration of the conditions affecting response, and a better description
      of outcome than a single point. There are no accepted firm criteria for the
      clinical relevance of differences observed. There is insufficient precision in
      outcome measures as they currently used to set up rules. It is proposed that the
      criteria under discussion are interesting and need to be further investigated.
      More data are needed on the expected range of response, the range of size of
      effect of drugs, the range of response categories to drugs, and the conditions
      affecting response. This information is available in the large databases from
      clinical trial programmes of the pharmaceutical industry and a coordinated
      examination of available databases would provide a fruitful basis for arriving at
      a worthwhile estimate of the clinical relevance of psychotropic drug effects.

PMID- 8998407
TI  - The effects of hydergine on the MAO activity of the aged and adult rat brain.
AB  - Despite the fact that hydergine has been used in the treatment of dementia for
      many years, its mechanism of action is still not clear. Current studies imply
      that the major effect of hydergine may be the modulation of synaptic
      neurotransmission rather than solely increasing blood flow as was once thought. A
      prominent feature that accompanies aging is an increase in monoamine oxidase
      (MAO) levels which results in decreased availability of catecholamines in the
      synaptic cleft. The aim of this study was to determine the effects of hydergine
      on the MAO activity in different brain regions (cortex, olfactory bulb,
      hypothalamus, hippocampus, striatum, cerebellum) of old (30 months) and adult (12
      months) male Sprague-Dawley rats. In cortex and olfactory bulb MAO levels were
      higher in the aged group. In hippocampus and hypothalamus hydergine treatment
      caused significant decreases in MAO levels. An interaction between age and
      hydergine treatment was observed in the hypothalamus, hippocampus and cerebellum.
      The hydergine effect was more pronounced in the aged group in the hypothalamus
      and cerebellum, and more pronounced in the adult in the hippocampus. Our findings
      imply that increased brain MAO activity in aging can be modified by hydergine
      treatment in some brain regions.

PMID- 8998409
TI  - [Effects of chloroquine on the replication of a murine retrovirus].
AB  - The wide use of chloroquine (Cq) for prophylaxis and chemotherapy of malaria in
      Africa, and the increased spread of AIDS in areas of this continent where malaria
      is endemic, raised the question of a possible interaction between chloroquine
      intake and HIV infection. Indeed, hydroxychloroquine and chloroquine itself have
      been shown to inhibit HIV-1 replication in vitro, hydroxychloroquine being
      proposed as a potential useful adjunctive therapy in the treatment of HIV-1
      infection. On the other hand, chloroquine has been reported to enhance the
      replication of Semliki forest and encephalomyocarditis viruses in a mouse model.
      In an attempt to elucidate Cq effect on retroviral replication, we have studied
      the effect of various concentrations of chloroquine in vitro (0.1 nmol/l to 25
      mumol/l) on Friend retrovirus (FV)-infected fibroblasts of mice and in vivo (2 to
      30 mg/kg) on FV-infected mice. No reduction in the number of virus foci was found
      in chloroquine-treated fibroblasts cultures. In chloroquine treated-infected
      mice, no differences were observed in the spleen weights, except an increase at
      10 mg/kg. A decrease in splenocyte virus titer was only observed at 10 and 30
      mg/kg. No differences in the median survival time was observed up to 30 mg/kg.
      The authors concluded that chloroquine seemed to have variable effects on viral
      replication in vivo depending on the dosage, but has no influence on the course
      of FV-induced disease.

PMID- 8998410
TI  - [Contribution of Trichrome Blue in the diagnosis of microsporidiosis].
AB  - Detection of microsporidia belongs to the usual coprologic and urine detection of
      parasites from HIV seropositive patients. To improve the identification of
      microsporidial spores, several stains have been used. Trichrome Blue stain has
      been evaluated in this study. We first compared Trichrome Blue stain to Weber's
      trichrome for the detection of microsporidia in smears of stools received from
      HIV seropositive patients. No difference of sensibility has been demonstrated
      between the two stains, and Uvitex 2B used on the same samples has confirmed
      these results. Then, Trichrome Blue stain has been used for the detection of
      microsporidial spores in other specimens (40 samples of nasal mucus, conjonctival
      samples, duodenal biopsy and urine), also Giemsa and Uvitex 2B. The advantage of
      Trichrome Blue stain is its ready-to-use presentation, and faster realisation at
      higher temperature. Trichrome Blue stain is interesting as a confirmation
      technique or for laboratories which do not have fluorescent microscopy equipment.

PMID- 8998411
TI  - [Anatomopathological aspects of 25 cases of bilharzial bladder cancer].
AB  - The anatomopathology of 25 cases of bilharzial cancer is reported involving 20
      men and 5 women. The macroscopic studies of the tumors revealed an unifocal,
      budding and infiltrating pattern. The significant type appeared to be the
      squamous carcinoma in 13 of the cases. All the 25 cases showed the presence of a
      bilharzial infestation with several patterns: tumoral clusters of squamous
      carcinoma and urothelial cells, clusters of scattered signet ring cells,
      elongated or undifferentiated atypical cells. The chronic inflammatory stroma
      contained bilharzia ova. The role played by metaplasia of the vesical urothelium
      is accepted by the majority of authors to explain the histogenesis of theses
      tumors.

PMID- 8998413
TI  - [Complications of diabetes mellitus at the Hospital Center of Ouagadougou].
AB  - It is a four year study (1991 January to 1994 December) on four hundred diabetic
      people in Ouagadougou, aiming to assess the complications observed in these
      patients. The search of these complications have been systematic during the first
      consultation and during the follow-up through clinical examination and
      complementary exams. Most of classic complications have been found and can be
      split in two groups: 1) acute complications which included: metabolic ones
      observed on 17.5% of the patients (ketoacidosis 5%, hypoglycemia 11.2% and
      hyperosmolar coma 1.2%); infectious complications observed on 79% of the
      patients. The high frequency of these complications testifies of the difficulties
      of the management, under-information and insufficient education of the patients;
      2) degenerative chronic complications including: microangiopathy: retinopathy
      (15.8%) and nephropathy (24.8%) which was complicated by chronic uremia in 9%
      cases; macroangiopathy in which: gangrene (7.5%), hypertension (20%), cardiac
      disease (8.7%), neurologic complications (35%) were the most frequent. These
      chronic complications accentuate mortality and morbidity linked to diabetes and
      increase the economical and social cost of this affection in a poor environment.

PMID- 8998412
TI  - [Diabetes mellitus at the National Hospital Center of Ouagadougou (Burkina
      Faso)].
AB  - The study, conducted over 4 years among 400 diabetic patients, reports the
      epidemiological and clinical aspects of diabetes mellitus at the National
      Hospital of Ouagadougou, Burkina Faso. Epidemiologically, diabetes mellitus
      affects men by 64% and women by 36%. 76% are over 40 y. o., whereas only 2.2% are
      under 20. Clinically, the classification of diabetic patients shows that 10.7%
      are insulin-dependent and 76.5% non insulin-dependent. No usual tropical diabetes
      has been found. The calcifications observed in 2.5% of cases were combined with
      chronic alcoholic pancreatitis. The classic triad (polyuria, polyphagia,
      polydipsia) led to diagnostic by 41% of the patients, whereas 27.5% have been
      identified when having complications, and 23% by a systematic check-up. Cardio
      vascular risk factors combined with diabetes have been found: obesity (28%), high
      blood pressure (20%), hyperuricaemia (14%), addiction to smoking (20%). The
      epidemiological characteristics, as well as the various clinical aspects, mostly
      complies with the observations of the african authors.

PMID- 8998414
TI  - [Epidemiological, clinical and evolutive aspects of gout in the internal medicine
      department at Ouagadougou (Burkina Faso)].
AB  - The study reports the epidemiology and signs of gout at Ouagadougou from a group
      of 35 patients observed in a department of internal medicine. The diagnosis of
      gout was based on Rome criteria. The most important epidemiological factors
      associated with gout were: obesity, hypertension, alcohol and diabetes. 75% of
      the patients were male. Gout was chronic polyarticular form and tophis were
      observed in 5 cases.

PMID- 8998416
TI  - [Fever of unknown origin (FUO) in the camps of Rwandan refugees in the Goma
      region of in Zaire (September 1994)].
AB  - After the outbreaks of cholera, dysenteriae, meningitidis of which the rwandese
      refugees have been the victims in August and September 1994 in the camps of the
      Goma's area (Zaire), the medical teams were confronted with a great number of
      fevers of unknown origin. In order to explore the possible etiologies, we have
      conducted a cases/controls study (n = 96). Clinically, the cases occur more
      frequently than controls headache (p < 0.001), splenomegaly (p = 0.02) and
      neutropeny (p < 0.001) Serologically, it has been constated non significantly
      difference between cases and controls, but prevalence of HIV-1 infections (19 and
      6%) and arbovirus (23 and 10%) infections are very high. Arbovirosis could
      explain, partially or associated with HIV and tuberculosis, the presence of these
      fevers undeterminated more than malaria or typhus epidemic.

PMID- 8998415
TI  - [Effects of malaria outbreak in a quarter of the city of Bobo-Dioulasso (Burkina
      Faso)].
AB  - Weekly malaria attack incidence rate has been studied from June to September 1993
      in a cluster of children and adults living in a quarter of the city of Bobo
      Dioulasso (Burkina Faso). The city is located in the savanna area with an average
      of 1000 mm rainfall in five months. In this recently built quarter at the
      outskirts, yearly average malaria transmission was of four infected bites mainly
      due to Anopheles gambiae. The medical team visited each week each included family
      (28 families, 290 persons). Malaria attack has been defined as a fever attack or
      the certitude of fever during the hours before, with clinical malaria-related
      signs, a patent parasitaemia and the lack of obvious other etiology. Parasitic
      density threshold of 2000 PRBC/mm3 for the children and adolescents, till 16
      years old and of 1,000 PRBC/mm3 for the adults, have been utilized for the
      definition of unquestionable malaria attack. 4128 medical observations have been
      done. 17 unquestionable malaria attacks have been observed in infants, children
      and adults with parasitic densities from 40,000 to 720,000 PRBC/mm3. 18 likely
      attacks were also observed with clinical signs but low density of Plasmodium. All
      were induced by P. falciparum. From June to the end of July the weekly incidence
      rate was five for one thousand and from August twelve for one thousand. In a
      place with a low transmission, the success of an infection is higher than in
      places with an intense transmission. This observation is of some importance for
      the control of the disease by reduction of the transmission.

PMID- 8998417
TI  - [Course of HIV2 seroprevalence at the National Hospital of Niamey (Niger)].
AB  - About the 25,368 serological tests done among the different groups of the
      population at the biological laboratory of the National Hospital of Niamey from
      March 1987 to May 1990, the author studied the seroprevalence evolution of the
      infection HIV2. A regular fall for the HIV2 appeared in this period. The author
      tries to explain this fall of the HIV2 in a country newly infected by the HIV by
      the lower infectivity of the HIV2 and/or a failure to adjust of this virus in
      Niger.

PMID- 8998418
TI  - [Prevalence of toxoplasmosis in Tananarive. Study conducted at the Pasteur
      Institute of Madagascar (PIM) on a sample of 2354 subjects].
AB  - The prevalence of Toxoplasma antibodies was studied in 2,354 individuals in
      Tananarive, at the Institut Pasteur of Madagascar. The seroprevalence among the
      malagasy population amounts to 52.1%. At the age of 10 years old, 36.3% of our
      sample have already acquired toxoplasma antibodies, proving an early infection.
      No differences have been observed between sexes. The toxoplasmosis prevalence
      among the female population coming from France, India and Pakistan and living in
      Tananarive seemed the same than in their home countries, whereas female
      population coming from China had shown a different seroprevalence compared to
      their home country.

PMID- 8998419
TI  - [Leptospirosis: a cause of pseudo-malarial fever in Gabon].
AB  - A first case of leptospirosis has been recently described in Gabon where
      bioclimatological characteristics could favour the transmission of that disease.
      Therefore, a search for antibodies to leptospirae was conducted among 55 military
      Frenchmen with unexplained fever during a four-month stay in Gabon. Three (5.5%)
      were positive with IgM levels attesting for recent contamination. A screening
      antigenic battery identified L. bataviae in two cases and L. sejroe in one case.
      The three patients were employed outside in the precedent weeks. Travelers are
      exposed to leptospirosis in numerous Third-World countries. Clinical and
      biological similarities between leptospirosis and P. falciparum malaria could
      induce misdiagnosis. Co-infection could also be encountered. Doxycycline, whose
      activity against P. falciparum is well known, is also effective against
      leptospirae. Therefore, this drug seems valuable for prophylactic and therapeutic
      actions in areas exposed to the both diseases.

PMID- 8998420
TI  - [Evaluation of the efficacy of Bacillus sphaericus Neid 1904 applied to
      previously cleaned gutters for Culex quinquefasciatus Say 1823 control in Abidjan
      (Cote d'Ivoire)].
AB  - In the framework of a pluri-institutional research project, led in Abidjan and
      aimed at defining measures to fight against mosquitoes in Abidjan area, a test to
      struggle for C. quinquefasciatus larvae was carried out in 1990. This test was
      conducted in Koumassi, which is one of Abidjan district, in which environmental
      conditions are very favourable for developing C. quinquefasciatus non-adult
      stages. The test consisted essentially in spreading a Bacillus sphaericus
      waterish solution (dose: 10 g.m-2) in previously cleaned gutters. The efficiency
      of the fight test was essentially assessed through: -the size of C.
      quinquefasciatus non-adult stages populations according to their development
      stage (egg, larva, nymph); -variations of both, C. quinquefasciatus females
      aggressive density and their physiological age. The gutters cleaning did not
      reduce significantly C. quinquefasciatus non-adult stages populations. On the
      other hand, the effectiveness of B. sphaericus was convincing. Its effects were
      tested to last for four weeks. The results were confirmed by the observations
      made on C. quinquefasciatus adult populations.

PMID- 8998421
TI  - Excess unwaged domestic work of female primary care physicians.

PMID- 8998422
TI  - Walk-in clinics. Medical heresy or pragmatic reality?

PMID- 8998423
TI  - [Experience in treating osseous sarcomas at the Research Institute of Pediatric
      Oncology, Cancer Research Center].
AB  - The paper presents clinical findings of 210 children with localized osteogenic
      sarcoma who have undergone various treatments. The authors consider neoadjuvant
      chemotherapy the method of choice, but by replacing tubular bone defects,
      endoprosthesis should be regarded the method of choice, which substantially
      reduces the time of rehabilitation and yields good (32.4%) and satisfactory
      (47.0%) functional results in most patients. In children with osteogenic
      sarcomas, the outcomes of treatment depend on its scope: 5-year survival was
      achieved in 68% of cases following multimodality treatment and in 36.2 and 14.0%
      after combined treatment and monotherapy alone, respectively. The retrospective
      analysis of treatment for morphologically verified Jung's sarcoma shows it
      expedient to implement a comprehensive program, including cyclic
      polychemotherapy, radiation of a damage focus in a dose of 57 Gy, obligatory
      surgical intervention into the operable sites, by assessing therapeutical
      pathomorphism and subsequent adjuvant polychemotherapy for at least 12-18 months.

PMID- 8998424
TI  - [Experience in treating Nephroblastomas].
AB  - The treatment of nephroblastomas which accounts for 72% of all malignant
      neoplasms in children is one of the topical problems of pediatric oncology. To
      detect the tumor at early stages of a tumorous process is one of the main
      conditions of successful treatment for nephroblastomas. The histological types of
      nephroblastoma, its international classifications and present-day treatment
      policy are given. A role of radiation treatment is shown at pre- and
      postoperative therapeutical stages. Drugs, their combinations, and the efficiency
      of polychemotherapy regimens in use are outlined. The importance of comprehensive
      examination of the patient to determine the extent of malignancy and to choose
      adequate antitumor treatment regimens is emphasized.

PMID- 8998425
TI  - [Mathematical survival analysis of children with acute nonlymphoblastic
      leukemia].

PMID- 8998427
TI  - [Prognosis of lymphogranulomatosis in children with mediastinal damage].
AB  - From 1982 to 1991, a total of 132 children with lymphogranulomatosis involving
      the mediastinum were studied. The comparative analysis of their survival was made
      on the basis of clinical and laboratory findings which might affect prognosis.
      Factorial analysis identified 9 unfavourable factors significantly influencing
      the survival rates. Their predictive value was defined from the informative rate
      (IR) and distributed in the following decreasing order: patient incompliance,
      Stage IV, the mediastinal thoracic index of more than 50%, the histological
      types: modular sclerosis and lymphoid depletion, the patient age of over 10
      years, higher haptoglobulin and ceruloplasmin levels, leukocytosis (greater than
      8 x 10(9)) g/l, diseases of the lung and pleura. The findings show it expedient
      to consider the above unfavorable factors in defining a risk group to apply a
      differential approach to treating patients with lymphogranulomatosis involving
      the mediastinum.

PMID- 8998426
TI  - [Social and medical aspects of multimodality therapy for lymphogranulomatosis in
      children].
AB  - The high efficiency of treatment of lymphogranulomatosis in children by the
      currently available protocols determines the necessity of assessing them in terms
      of the quality of further life. The opportunity of creating a life and having the
      offspring, that of getting education and a profession are one of the main
      characteristics of the quality of life. The data on the reproductive function and
      social adaptation of 443 children receiving multimodality treatment for
      lymphogranulomatosis by 3 protocols (from 1976, 1978, and 1987). Two hundred and
      fifty eight individuals were 18 years old or more. Sixty four former patients
      have 88 children who are all healthy. The treatment performed in childhood
      intensively, which yielded a complete effect, exerts no substantial impact on the
      formation and performance of their reproductive function. The former patients
      have a high intellect, without limitations in getting professions, and they are
      easily adaptable to the changing social conditions.

PMID- 8998428
TI  - [Factors influencing the survival of children with Non-Hodgkin's disease].
AB  - Based on the results of examinations and treatment of children aged under 15
      years, the authors analyze the factors influencing the survival of patients with
      non-Hodgkin's disease. The stage, site, histological structure, cytological type
      of a tumor, signs of intoxication, levels of lactate dehydrogenase, total protein
      and albumin, sex, and the count of leukocytes were found to affect the survival
      of children with non-Hodgkin's disease. Moreover, in patients receiving, in
      addition to chemoradiation, therapy, interferon preparations, and T-activin, the
      survival was much higher than that in untreated children. Intensified treatment
      with higher-dose methotrexate largely altered the predictive value of the
      majority of these factors, as evidenced by the lower informative value while
      analyzing by the method of Shennon. The findings should be used in developing
      treatment regimens for children with non-Hodgkin's disease.

PMID- 8998429
TI  - [Multimodality treatment for retinoblastoma in children].
AB  - A comprehensive programme was developed for the treatment of uni- and bilateral
      retinoblastoma in children with due regard to the disease stage by the TNM
      system. The use of the current sources of teletherapy and cyclic polychemotherapy
      expanded indications for organ-saving therapy at most common stages. Treatment by
      the program was performed in 202 patients, including 125 children with unilateral
      damage and 77 with bilateral damage. An attempt made treat 140 (75%) children at
      the first stage. More than 70% of cases were diagnosed as having disease stage T3
      in one or two stage, while such patients underwent ocular enucleation. A complete
      or partial (more than 50%) tumor regression without signs of its progression for
      2 years or more was achieved in 62% of cases. At the first stage of therapy,
      conservative therapy insignificantly affected the children's longevity in
      uncomplicated cases, which is particularly important in bilateral involvement,
      while this preserved the organ of vision in more than half the patients (62%).
      Five-year survival was 92 and 82% in unilateral retinoblastoma surgically treated
      and untreated, 83 and 84%, respectively. Adequate multimodality treatment brought
      about low incidence rates of recurrence and metastasis (10%) in conservative
      therapy and 7.7% among all patients.

PMID- 8998430
TI  - [Formation and development of medical science in Siberia].

PMID- 8998431
TI  - [Comparative characterization of altered activity of lysosomal cysteine
      proteinases in various leukocytic fractions inpatients with chronic lymphocytic
      leukemia].
AB  - There was a pronounced decrease in the general activity of cathepsins C and L
      and, to a lesser extent, cathepsin B in the lymphocytes of patients with Stage II
      chronic lymphocytic leukemia. The activity of cathepsins C and L in the
      granulocytes of these patients was significantly lower than the control values.

PMID- 8998432
TI  - [Prediction of the epidemiological efficiency rate of preventive antiviral drugs
      from laboratory findings].
AB  - Based on the dose-response dependence represented as a generating distribution
      function of infecting doses of a pathogen, a value for the epidemiological
      efficiency rate of preventive agents was derived. For an arbitrary distribution
      of infecting doses, EEC mean values is shown to always no greater than 1:
      ED50v/ED50w where ED50v and ED50w are 50% of the infective doses of the pathogen
      assessed for those treated with the agent and intact persons, respectively. This
      relation is also valid when differences in pathogenic resistance are determined
      not only due to the use of drugs, but for any other variables (age-, sex-specific
      and other factors). This was verified by experiments.

PMID- 8998433
TI  - [History of Russian medical primatology].

PMID- 8998435
TI  - Common managed care terms.

PMID- 8998434
TI  - [Pediatric oncology: unity of science and clinic].
AB  - The paper outlines progress made in pediatric oncology in Russia in the past 30
      years. Studies dealing with the clinical presentation, diagnosis, and treatment
      of malignant neoplasms in children have revealed great differences in the
      clinical course of malignant processes in childhood due to anatomic and
      physiological features of a child's developing organism and to the prevalence of
      more aggressive and high-grade tumors--sarcomatous and germinogenic. In children,
      most tumors are congenital. The influence of exogenous and endogenous factors on
      the mother and the fetus brings about either fetal death, or a neoplastic process
      of developmental malformations and more frequently their combination.

PMID- 8998436
TI  - Four principles of transformation thinking.

PMID- 8998437
TI  - Measuring your nursing home's orientation to quality.

PMID- 8998438
TI  - Competency assurance in long-term and subacute care.

PMID- 8998439
TI  - Tired teams? We're in this together.

PMID- 8998440
TI  - Creating graphs from spreadsheets.

PMID- 8998442
TI  - Disbanding the quality improvement team.

PMID- 8998441
TI  - Whose role is it? In my opinion.

PMID- 8998443
TI  - From educator to internal consultant: making the shift.

PMID- 8998444
TI  - Team learning for world championship care.

PMID- 8998445
TI  - Extending core courses across the continuum.

PMID- 8998446
TI  - Preview and review: pretesting and posttesting made simple.

PMID- 8998448
TI  - More than survival: the three T's it took.

PMID- 8998447
TI  - Engendering collegial caring: a mandate for staff development.

PMID- 8998449
TI  - [Antioxidant protection of syrian hamster cells transformed in vitro by various
      agents].

PMID- 8998450
TI  - [The effect of antibodies against nerve-specific protein S100 on calcium channels
      in the somatic membrane of snail neurons].

PMID- 8998452
TI  - [Analysis of the mutagenicity of drinking tap water from several Moscow districts
      and Moscow region].

PMID- 8998451
TI  - [Modified chitosan as a stimulant of reparative skin regeneration].

PMID- 8998453
TI  - [Heterospecific social factors influencing the rate of sexual maturation of
      Campbell's hamsters (Phodopus campbelli Thomas, 1905): the role of cross-rearing
      and secretion of the midventral gland of male Djungarian hamsters (Phodopus
      sungorus pallas, 1773)].

PMID- 8998454
TI  - [Genomic effect of low doses of prolonged gamma-irradiation of mice and its after
      effect].

PMID- 8998457
TI  - [Low-energy He-Ne-laser-induced neurochemical changes during brain
      ischemia/reperfusion and their integral estimation using a factor analysis
      model].

PMID- 8998455
TI  - [Frequency of cells with semi-bridges in cell populations in vivo].

PMID- 8998456
TI  - [Identification in the rat brain of cyclo-prolylglycine, a novel endogenous
      peptide with nootropic activity].

PMID- 8998458
TI  - [Changes in liver structures of animals subjected to repeated prolonged
      hyperbaria].

PMID- 8998459
TI  - Evaluation of radioiodo-4-amino-N-[1-[3-(4-fluorophenoxy)-propyl]-4- methyl-4
      piperidinyl]-5-iodo-2-methoxybenzamide as a potential 5HT2 receptor tracer for
      SPE(C)T.

PMID- 8998460
TI  - Radioligands for PET studies of central 5-HT receptors and re-uptake sites-
      current status.

PMID- 8998461
TI  - Mechanism-based strategies for mapping heart sympathetic nerve function.

PMID- 8998462
TI  - Relevance of PET/SPET tracers for cardiac neurotransmission.

PMID- 8998464
TI  - An HPLC-method for determination of ligand metabolism during PET studies with
      [11C]metaraminol and [11C]norepinephrine.

PMID- 8998463
TI  - Some new methods for the synthesis of cardiac neurotransmission PET radiotracers.

PMID- 8998465
TI  - 76Br-MBBG, a PET radiotracer to investigate the norepinephrine neurological and
      vesicular transproters in the heart.

PMID- 8998466
TI  - PET examination of the monkey heart with high specific radioactivity
      [11C]norepinephrine and [11C]metaraminol.

PMID- 8998467
TI  - Sources of radiochemical impurities in the 99mTc/S-unprotected MAG3 system.
AB  - With the aim of obtaining a general insight into the technetium/S-unprotected
      MAG3 system, the reactions of technetium with the unprotected MAG3 ligand, both
      at c.a.- and n.c.a.-level, were investigated. Based on a profound knowledge of
      the reaction route and the TcMAG3 complexes, sources of by-products were
      identified and eliminated as far as possible. Only a small percentage (< 5%) of
      intermediate Tc-MAG3 complexes occurs, but this may increase by improper handling
      of the kit, such as insufficient reaction time. In conclusion, two kinds of
      impurity may occur in the Tc/MAG3 kit: One is derived from impurities in the
      ligand (MAG3 disulphide), which can be excluded by careful preparation and
      storage. The other is caused by insufficient reaction time according to the
      scheme (Fig. 3) during the labelling procedure. Its content can be minimized by
      optimization of the reaction time. A reaction time of at least 10 minutes gives
      about 98% of the renal agent.

PMID- 8998468
TI  - Radiochemical purity of 99mTc-HM-PAO: critical parameters during kit preparation.

PMID- 8998469
TI  - Metabolic and pharmacokinetic considerations in the design of 2-phenyl
      substituted metyrapone derivatives: 2-methoxyphenylmetyrapone as a radioligand
      for functional diagnosis of adrenal pathology.

PMID- 8998471
TI  - New radio-tracers and methods of quality assurance for nuclear medicine
      applications. Villigen, Switzerland, 6-7 October 1994. Proceedings.

PMID- 8998470
TI  - Comparison of non-isotopic exchange methods for n.c.a. labelling of 2-iodophenyl
      metyrapone.
AB  - The Cu(I)-assisted aromatic halogen exchange proved useful for preparation of
      macroscopic amounts of 2-iodophenyl-metyrapone as well as for the n.c.a.
      radioiodinated analogue. Semi-preparative HPLC-isolation provided the compound
      with high purity for use as chromatographic standard and for the determination of
      the inhibition constant of the 2-iodo-analogue. The non-isotopic exchange led to
      a high specific activity (> 5000 GBq/mumol) of 2-[123I]iodophenyl-metyrapone. A
      reaction in acetic acid at elevated temperatures proved superior to an exchange
      in aqueous solution with in-situ reduction of Cu2+. Even without Cu+ high
      radiochemical yields of > 80% were obtained, while addition of Cu+ provided the
      radiotracer with 95% radiochemical yield within 5 minutes in acetic acid.

PMID- 8998472
TI  - Synthesis of nor-beta-CIT, beta-CIT and trimethylstannyl-beta-CT.

PMID- 8998473
TI  - Comparison of [11C]methyl triflate and [11C]methyl iodide in the synthesis of PET
      radioligands such as [11C]beta-CIT and [11C]beta-CFT.

PMID- 8998474
TI  - The metabolite pattern of [123I]beta-CIT determined with a gradient HPLC method.

PMID- 8998475
TI  - N.c.a. radiosynthesis of [123,124I]beta-CIT, plasma analysis and pharmacokinetic
      studies with SPECT and PET.

PMID- 8998476
TI  - Evaluation of [123I] beta-CIT binding with SPECT in controls, early and late
      Parkinson's disease.
AB  - The main neuropathological feature in Parkinson's disease (PD) is a severe
      degeneration of the dopaminergic neurons in the substantia nigra resulting in a
      loss of dopamine in the striatum. Recently, a new radioligand (beta-CIT) for
      single photon emission computed tomography (SPECT) became available for in vivo
      imaging of the dopamine transporter on nerve endings of dopaminergic neurons in
      the striatum. The present results demonstrate that [123I]-beta-CIT SPECT allows a
      discrimination between early and late PD patients. In our opinion, these
      preliminary data suggest that [123I]-beta-CIT SPECT should be used from now on in
      longitudinal studies (such as the DATATOP study) in which the effects of
      (putative) neuroprotective interventions in PD are monitored.

PMID- 8998477
TI  - 76Br-beta-CBT, a PET tracer for investigating dopamine neuronal uptake.

PMID- 8998479
TI  - AWHONN member recounts tale of joy, sorrow in Vietnam.

PMID- 8998478
TI  - [123I/18F] N-(2-aminoethyl)-5-halogeno-2-pyridinecarbox-amides, site specific
      tracers for MAO-B mapping with SPECT and PET.
AB  - After the successful 123I-labelling of Ro 43-0463 the new radiopharmaceutical was
      tested in animals and humans. Both investigations proved the binding of the
      labelled compound to cerebral MAO-B. SPECT investigations resulted in an imaging
      of the MAO-B distribution in the human brain. This prompted us to develop the
      labelling of this type of MAO-B inhibitor with 18F enabling us to transfer our
      results to PET.

PMID- 8998480
TI  - What is GOG and how are nurses involved in developing and utilizing GOG
      protocols?

PMID- 8998481
TI  - AWHONN nurses delivery one-to-one care.

PMID- 8998482
TI  - How can women's health nurses recognize patients at risk for eating disorders?

PMID- 8998483
TI  - Pregnancy after infertility: helping couples cope with the transition to
      parenthood.

PMID- 8998484
TI  - Epidural analgesia and the role of the obstetric nurse.

PMID- 8998485
TI  - What should be taught to new parents about care of their son's uncircumcised
      penis?

PMID- 8998486
TI  - What process can be used if I think a patient's treatment plan is unethical?

PMID- 8998487
TI  - Basal cell carcinomas cause little handicap.
AB  - Basal cell carcinoma (BCC) is the most common type of skin cancer and the
      incidence of BCC is expected to rise, with increased demand on dermatology
      resources. Little is known of the effect on people's lives of having skin cancer.
      The aim of this study was to quantify the handicap caused gy basal cell
      carcinomas before and after therapy. Forty-four patients (22 males, mean age = 65
      yrs, range = 35-81 yrs) with 48 BCCs were recruited and 37 patients completed the
      study. Each patient completed the UK Sickness Impact Profile (UKSIP) and the
      Dermatology Life Quality Index (DLQI) at the initial visit to the dermatology
      clinic, 1 week after treatment and 3 months after treatment. Lesions had been
      present for a mean of 25 months (range = 1-240 months), their mean diameter was
      9.6mm (range = 3-35mm) and the sites were head and neck (79%), trunk (17%) and
      limbs (4%). There was no relationship between the quality of life score and size
      of lesion. Overall the scores at presentation were very low, rising 1 week after
      treatment and falling to below the initial scores at 3 months (mean UKSIP 0.4%,
      0.7%, 0.13%; mean DLQI 5.3% 8.7%, 1.2%). BCCs cause little handicap. This may
      explain the delay in seeking medical attention and should be considered in
      planning public health education about BCCs.

PMID- 8998488
TI  - Using the SF-36 and Euroqol on an elderly population.
AB  - An important methodological issue in measuring health-related quality of life is
      whether instruments such as SF-36 and EQ can be used on an elderly population.
      This paper aims to test the completion, reliability and validity of the SF-36 and
      Euroqol on an elderly female population, and to compare them with the OPCS
      Disability Survey. Three hundred and eighty women aged 75 and over participated
      in a randomized controlled trial of the use of clodronate provided the sample. As
      part of the trial, patients were asked to complete the UK SF-36 and Euroqol, and
      the OPCS disability survey instrument administered by interview in a hospital
      clinic at baseline. A random subsample of respondents were retested six months
      later. The SF-36 achieved poorer levels of completion by dimension (68.1%-88.9%)
      than the OPCS (99.2%) and Euroqol (84%-93.5%) instruments. There were no major
      floor effects in the distribution of scores, except for the role dimensions of SF
      36. Correlation between test-retest were significant for all instruments, but
      lower for the role dimensions and social functioning of SF-36, and these
      dimensions also had 95% Cls for the mean differences in excess of 10 points.
      There was substantial agreement between the three instruments, and evidence for
      their construct validity against age and recent use of health services. The
      sensitivities of the instruments were tested through hypothetical changes in
      health status. There was some evidence of greater sensitivity to lower levels of
      morbidity in the SF-36. Where brevity is required and the health changes are
      expected to be substantial, then EQ may be sufficient. For greater sensitivity SF
      36 seems to have an advantage, however lower completion rates and problems with
      consistency suggest it requires adaptation. One solution would be to use
      interviewer administration. Another would be to change the SF-36 to make it more
      suitable for use in elderly people, although this may reduce its usefulness as a
      generic instrument.

PMID- 8998489
TI  - Quality of life in early adolescence: a sixteen-dimensional health-related
      measure (16D).
AB  - While data on the health-related quality of life (HRQOL) of adults are
      accumulating, very little is known about the HRQOL--and especially the perceived
      HRQOL--of children. In our study we introduced a 16-dimensional, generic self
      assessment measure of HRQOL (16D) for early adolescents, and demonstrated its use
      with four populations of children aged 12-15: (1) 239 normal schoolchildren, (2)
      patients waiting for organ transplantation (n = 5), (3) patients with genetic
      skeletal dysplasias (n = 19), and (4) patients with epilepsy (n = 32). The HRQOL
      profiles of the patients differed significantly according to the diagnosis,
      giving support to its construct validity. The reliability of the measure was
      high: its repeatability coefficient was 91%. The quality of life ratings of the
      healthy boys and their parents differed on the dimensions of distress, vitality,
      speech, mental function, and discomfort and symptoms (p < 0.05). In addition,
      there were significant differences in the health-related valuations between the
      girls, boys and their parents. We conclude that the assessment of quality of life
      of adolescents should be based on data collected from the adolescents themselves.
      Further, the 16D is so far the only generic HRQOL measure designed specifically
      for this purpose. It is capable of differentiating the HRQOL of healthy
      adolescents as well as patients with various diagnoses. Our experience also
      indicates that it is easy to use, yet it seems comprehensive, reliable, and
      valid.

PMID- 8998490
TI  - Measurement of quality of life in localized prostatic cancer patients treated
      with radiotherapy. Development of a prostate cancer-specific module supplementing
      the EORTC QLQ-C30.
AB  - The purpose of this study was to construct a multidimensional self-administered
      quality of life questionnaire specific to prostate cancer within the EORTC
      framework and to test its applicability, clinical relevance and psychometry. A
      proposed prostate cancer-specific module and the standardized EORTC QLQ-C30
      version 1.0 were tested in 192 post-irradiated patients. Psychometric analyses
      comprised item convergent and discriminant validity for scaling success, analysis
      of the internal consistency of the multi-item scales and the validity of the
      scales. The clinical relevance was explored by correlation analysis including
      disease and treatment related parameters. The minimum psychometric criteria were
      met. The measurements revealed problem areas in sexuality with a mean score of 54
      (SD = 33) on a 0-100 scale, and in bowel functioning, scoring 25 on average (SD =
      17). Urinary complaints only reached a mean score of 6 (SD = 19). Compared to
      earlier measurements on untreated or irradiated localized cancer patients using
      the same core questionnaire, the physical and psychological scales showed higher
      values and the symptom scales lower symptom burden. The constructed questionnaire
      seems applicable and clinically relevant. The psychometric analysis revealed a
      few items to be revised. Patients with localized prostatic carcinoma treated with
      radiotherapy have a high quality of life compared to patients with localized
      cancer of other origin.

PMID- 8998491
TI  - Responsiveness of the SF-36 and a condition-specific measure of health for
      patients with varicose veins.
AB  - Approaches to measuring patient perceptions of outcome for varicose veins were
      tested using a postal questionnaire incorporating a clinically derived specific
      measure of varicose veins severity and the SF-36 health survey. The questionnaire
      was administered to 373 patients with varicose veins, 287 of whom had been
      referred to hospital for their varicose veins and 86 who had just consulted a
      general practitioner for the condition. The response rate exceeded 75%. Test
      retest reliability was assessed by mailing patients a similar questionnaire at
      two weeks. The validity of the two instruments was assessed by comparing patient
      scores to general practitioner ratings of symptom severity and complications
      associated with varicose veins. Standardized response means (mean change in
      scores divided by the standard deviation of the change in scores) were used to
      quantify and compare the responsiveness of the two measures. Levels of test
      retest reliability, as assessed by the intraclass correlation coefficient, were
      acceptable and the instruments appear to have good levels of validity. Patients
      who were or were not admitted to hospital for surgery on their veins had
      significant improvements in perceived health status on both the specific measure
      and the SF-36. The specific measure was the most responsive to changes in health
      status for both patients who were admitted to hospital for surgery and those
      receiving alternative forms of management. These two approaches might be suitable
      as part of a package of outcome measures for use in clinical trials to assess the
      effectiveness of different interventions for varicose veins.

PMID- 8998492
TI  - Toward a general model of health-related quality of life.
AB  - A health-related quality of life (HRQOL) model that fitted data collected in
      previous studies from two separate samples--patients with chronic physical
      illness and patients with chronic mental illness--was adapted and tested on a
      representative sample drawn from the normal population. This model, which implied
      that both physical and mental health influenced number of friendships, personal
      growth, and job satisfaction, fitted the data very well. However, an alternative
      model reversing the directions of the pathways so that friendships, personal
      growth, and job satisfaction affected physical health and mental health, with the
      latter two having a mutual effect on each other, fitted the data even better.
      This suggests that, although a medical model of HRQOL may be more important when
      it comes to alleviating illness, a psychosocial model of HRQOL may be more
      important when it comes to maintaining health and preventing illness. Moreover,
      the fact that essentially the same five-factor structural model fits three
      distinct populations, healthy and unhealthy, suggests that there may be a general
      model of quality of life applicable to all populations. The implications of these
      findings for clinical theory, policy, and practice are discussed.

PMID- 8998494
TI  - Quality of life in gastric cancer prior to gastrectomy.
AB  - A growing number of surgical trials include quality of life variables in the
      overall assessment of outcomes. This is believed to broaden the criteria for
      choice of treatment and the evaluation of treatment regimens. The present study
      is a baseline evaluation of the health-related quality of life in patients with
      gastric cancer facing surgery. The quality of life in these patients was related
      to that of other patient groups referred for surgical interventions and general
      population groups. Our study included 103 consecutive patients with carcinoma of
      the stomach considered amenable to a curative major surgical procedure. The
      quality of life evaluation was based on a battery of questionnaires, covering
      general body symptoms, mood level and functional limitations. Patients with
      gastric cancer reported more neurasthenic complaints such as reduced sexual
      interest, insomnia and poor appetite as well as a lower mood level than the
      general population. The gastric cancer group also showed a markedly lower mood
      level in comparison with a group of cancer survivors 2-3 years after diagnosis
      and patients with intermittent claudication. The mental well-being of gastric
      cancer patients matched that of cancer survivors with one or more recurrences.
      Overall, 25% of the gastric cancer patients reported functional limitations
      regarded as clinically significant. Patients with intermittent claudication
      reported more and patients with small cell lung cancer markedly more limitations.
      We conclude that although patients with gastric cancer showed a low level of
      limitations on average, problems in the areas of sleep/rest, home management and,
      especially, eating were frequently reported.

PMID- 8998493
TI  - The Diabetes Health Profile (DHP): a new instrument for assessing the
      psychosocial profile of insulin requiring patients--development and psychometric
      evaluation.
AB  - The aim of the studies was to evaluate the psychometric properties and construct
      validity of the Diabetes Health Profile (DHP-1). Content for the DHP-1 was
      derived following in-depth interviews with 25 insulin dependent and insulin
      requiring patients, a review of the literature and discussions with health care
      professionals. Initial analysis of the factor structure of the DHP-1 was carried
      out on the responses of 239 insulin dependent and insulin requiring patients,
      with a mean age of 40.85 years (SD = 13.0), resulting in a 43 item three factor
      solution. The 43 item version of the DHP-1 was completed by 2,239 insulin
      dependent/requiring patients (mean age = 39.8, SD = 10) years. Fifty-one per cent
      were men. A forced three factor Principal Factoring Analysis with varimax
      rotation was carried out. Eleven items were excluded with item factor cross
      loadings > 0.30 or item factor loadings < 0.30. PAF analysis of the 32 items
      resulted in a three factor solution accounting for 33% of the total explained
      variance. The three factors were interpreted as Psychological Distress, Barriers
      to Activity and Disinhibited Eating. Factor congruence between subsamples were:
      Psychological distress (0.93), Barriers to Activity (0.93) and Disinhibited
      Eating (0.99). Coefficients of congruence between men and women were 0.94, 0.92
      and 0.99 for Psychological Distress, Barriers to Activity and Disinhibited Eating
      respectively. Internal consistency of the three factors (Cronbach's alpha) were:
      Psychological Distress (0.86), Barriers to Activity (0.82), and Disinhibited
      Eating (0.77). Construct-convergent validity was investigated on a sample of 233
      insulin dependent and insulin requiring patients (mean age = 51.46 years).
      Psychological Distress and Barriers to Activity subscales correlated with the
      Hospital Depression and Anxiety Scale = 0.50 to 0.62, p < 0.01) and subscales of
      the SF-36 (range: r = -0.17 to -0.62, p < 0.01). These findings lend support to
      the construct validity and reliability of the DHP-1 and that it is suitable for
      further development.

PMID- 8998495
TI  - Measurement of quality of life in women with breast cancer. Development of a Life
      Satisfaction Questionnaire (LSQ-32) and a comparison with the EORTC QLQ-C30.
AB  - The purpose was to develop and validate a new instrument suitable for measuring
      perceived quality of life in women with breast cancer. The instrument is to be
      used within conventional cancer therapy as well as in complementary care, and is
      called the LSQ-32 (Life Satisfaction Questionnaire). The subjects were 362 women
      with breast cancer in all cancer stages. Cronbach's alpha reliability coefficient
      of the LSQ was 0.89. The construct validity was estimated by a principal
      component analysis. Six orthogonal factors were identified: (1) 'Quality of
      family relation', (2) 'Physical symptoms', (3) 'Socioeconomic situation', (4)
      'Quality of daily activities', (5) 'Sickness impact' and (6) 'Quality of close
      friend relation'. The criterion-related validity was estimated by comparing the
      LSQ-32 and the EORTC QLQ-C30. The scales/items of the EORTC QLQ-C30 were
      represented in the LSQ-32, but the factors 'Quality of family relation' and
      'Quality of close friend relation' were not found in the EORTC QLQ-C30. It was
      concluded that the LSQ-32 as well as the EORTC QLQ-C30 are valuable tools in the
      measurement of quality of life in women with breast cancer. The LSQ-32, however,
      also contains an existential factor.

PMID- 8998496
TI  - The impact of human immunodeficiency virus (HIV) infection on quality of life in
      a multiracial South African population.
AB  - We set out to document quality of life in South African HIV subjects, using the
      Medical Outcomes Survey (MOS) SF-36 instrument, and to determine whether this was
      affected by race, gender or clinical stage of disease. A cross-sectional survey
      of 134 HIV outpatients (42 White, 49 Mixed race, 43 Black) and 114 healthy non
      medical hospital personnel (36 White, 37 Mixed race, 42 Black) was carried out at
      a referral centre for HIV patients in the Western Cape region of South Africa.
      Scores on eight scales measuring different aspects of quality of life were
      calculated. Black female controls scored significantly lower on all scales (p <
      0.05) except physical function. HIV-infected subjects of Mixed race (both
      genders) reported poorer physical function (p < 0.05) but no other scale was
      affected by race. HIV subjects scored significantly lower than controls on all
      scales (p < 0.01); the majority of the decline in function occurred early in
      disease by WHO stages 1 and 2. We conclude that HIV-infection impacts early on
      all aspects of quality of life and that this impact is largely independent of
      racial origin.

PMID- 8998497
TI  - The use of two measures of health-related quality of life in HIV-infected
      individuals: a cross-sectional comparison.
AB  - Two measures of health-related quality of life in 65 HIV-infected individuals
      were compared in a cross-sectional design. The Quality of Well-Being Scale (QWB)
      results in a single score ranging from death to perfect health. The MOS-HIV
      Health Survey (MOS-HIV, 34-item version) gives scores in 11 dimensions. The QWB
      score distinguished subjects with AIDS from those who were asymptomatic (p =
      0.027). For the seven multi-item scales of the MOS-HIV, Cronbach's alpha ranged
      from 0.85-0.95, indicating good internal consistency reliability. Clinical HIV
      infection status was significantly associated with the dimensions of Overall
      Health (p = 0.002), Role Function (p = 0.022), Social Function (p = 0.037),
      Energy/Fatigue (p = 0.027) and Health Distress (p = 0.025). All eleven dimensions
      of the MOS-HIV were significantly correlated with the QWB score (Spearman's
      coefficient = 0.405-0.670; for all, p < 0.01) and the QWB score could be
      predicted from the MOS-HIV dimension scores using multiple regression. The QWB
      and the MOS-HIV may be useful in assessing health-related quality of life in
      patients infected with HIV.

PMID- 8998500
TI  - Cell fate in the development of the Arabidopsis flower.
AB  - The Arabidopsis flower consists of four concentric whorls of organs. The first
      (outermost) whorl consists of four sepals and the fourth (innermost) whorl is
      made up of two carpels. Cell fate in the first and fourth whorls was studied
      using X-ray-induced yellow ch-42 sectors. Sector boundaries were found to be non
      random around the two whorls and four generalizations relating the marked and
      unmarked tissues were deduced. In the sepal and carpel whorls the smallest
      sectors of marked and unmarked tissue were found to be one half of a sepal and
      one half of a carpel, respectively. A detailed frequency-distance map of the
      floral primordium was made and found to be a ridge with the fourth whorl carpels
      at the summit and the first whorl transverse sepal pair at the base.
      Consideration of: the rate of loss of chimerism in the inflorescence meristem,
      the frequency-distance across the flower and the frequency-distance between
      successive flowers, was used to produce an abstract model of the inflorescence
      meristem.

PMID- 8998499
TI  - Arabidopsis mutants showing an altered response to vernalization.
AB  - Flowering in many plant species is accelerated by a long period of cold
      temperature, known as a vernalization period. This research investigates how this
      cold temperature signal is perceived by plant cells and the mechanism by which it
      influences the transition to flowering. Mutagenesis of the late-flowering,
      vernalization-responsive, Arabidopsis mutant, fca, has yielded five independent
      mutations (termed vrn mutations) conferring an altered vernalization response.
      Allelism tests showed that these mutations fall into at least three
      complementation groups defining three loci named VRN 1, 2 and 3. The vrn1 and
      vrn2 mutations did not affect the acclimation response as judged by expression of
      cold-induced transcripts and freezing tolerance assays. vrn1-1 affected the short
      day vernalization response of Landsberg erecta and reduced the vernalization
      response of other late-flowering Arabidopsis mutants. The acceleration of
      flowering by GA3 was not affected by vrn1-1. The VRN 1 locus was mapped to
      chromosome 3.

PMID- 8998498
TI  - Assessing quality of life in chronic non-specific lung disease--a review of
      empirical studies published between 1980 and 1994.
AB  - Chronic non-specific lung disease (CNSLD), a chronic disease with considerable
      prevalence and mortality rates, is not only a medical problem, it also has
      significant psychological and social consequences for the patients concerned.
      Quality of life research on CNSLD has been rather underdeveloped for quite a long
      period of time, but has recently become an important topic in research as well as
      in patient care. In order to get insight into the state of the art of empirical
      research on quality of life (QOL) in CNSLD, a review of the literature between
      1980-1994 on this topic is presented. Special attention is paid to definitions
      and operationalizations of the QOL concept as well as on questionnaires used to
      assess QOL and the aims of QOL research. Analysis reveals that QOL is seldom
      defined clearly and is operationalized in a variety of ways. Most studies have a
      descriptive nature or pertain to clinical trials. The negative impact of CNSLD on
      QOL is well-documented and shows the importance of incorporating assessment of
      QOL in research as well as in patient care. Future research is called for, which
      should be theory-driven, taking into account recent developments concerning
      disease-specific measures of QOL.

PMID- 8998502
TI  - NIH's John Watson battles bureaucracy for research.

PMID- 8998501
TI  - N-linked oligosaccharide processing is not necessary for glycoprotein secretion
      in plants.
AB  - The role of N-glycans in the secretion of glycoproteins by suspension-cultured
      sycamore cells was studied. The transport of glycoproteins to the extracellular
      compartment was investigated in the presence of a glycan-processing inhibitor,
      castanospermine. Castanospermine has been selected because it inhibits
      homogeneously glycan maturation in sycamore cells and leads to the accumulation
      of a single immature N-glycan. The structure of this glycan has been identified
      as Glc3Man7GlcNAc2 by labeling experiments, affinity chromatography on
      concanavalin A-Sepharose and proton NMR. In contrast with previous results
      showing that N-glycosylation is a prerequisite for secretion of N-linked
      glycoproteins, this secretion is not affected by the presence of castanospermine.
      As a consequence, the presence of this unprocessed glycan is sufficient for an
      efficient secretion of glycoproteins in the extracellular compartment of
      suspension-cultured sycamore cells.

PMID- 8998504
TI  - [Genetic determinism of sperm production in bulls].
AB  - In this study, the relationships between semen production and semen quality of
      Normande bulls in performance test station and in two IA centers were evaluated
      and the genetic characteristics and evolution of semen production of young bulls
      in station were calculated. When analysing the relationship between semen
      production of young and adult Normande bulls data from 2,677 bulls between 12 and
      15 months of age exhibited large difference between 5 groups corresponding to an
      overall classification given by a technician. Correlations between corrected data
      collected in station and bull effect estimates in AZ studs were quite high for
      volume and concentration, and moderate for motility and number of doses per
      ejaculate or per month. The correlations calculated are underestimates of the
      true ones, as bulls with undesirable semen characteristics were culled before
      entering AI. Nevertheless, among the remaining bulls, important differences (40%)
      in semen output were observed between extreme groups, as classified by the
      technician. Genetic parameters evaluated from a subset of 1957 young Normande
      bulls confirms earlier results reported in the literature. The heritability of
      the average volume of the ejaculate is very high (h2 = 0.65 +/- 0.09). Sperm
      quality traits are moderately heritable (h2 = 0.23 +/- 0.08 for motility score to
      0.37 +/- 0.09 for concentration) and strongly correlated. Total percentage of
      abnormal spermatozoa estimated from a selected subset seems less heritable (h2 =
      0.19 +/- 0.07). A Best Linear Unbiased Prediction was then carried out on the
      records from 2,387 bulls using these estimates. No clear genetic trend could be
      detected in the population, although the phenotypic selection performed should be
      efficient. This apparent contradiction results from the increasing influence in
      the breed of one family of heavily used bull sires with a poor genetic merit on
      sperm production traits.

PMID- 8998503
TI  - [Molecular biology of the persistent Mullerian duct syndrome].
AB  - The persistent Mullerian duct syndrome, characterized by the presence of uterus
      and tubes in otherwise normally masculinized 46,XY males, is a familial autosomal
      recessive disorder due to defects of synthesis or action of anti-Mullerian
      hormone. We have performed molecular studies in a total of 38 families and we
      have identified the basis of the condition, namely 16 anti-Mullerian hormone and
      16 anti-Mullerian hormone receptor mutations, in 32 families.

PMID- 8998505
TI  - [Male XX syndrome: contribution of the caprine and porcine models].

PMID- 8998506
TI  - [Sex determination and transgenesis].

PMID- 8998507
TI  - [Prognostic value of high FSH concentrations].
AB  - Ovarian age is a major determinant of success in assisted reproductive
      technologies. The number and quality of oocytes retrieved directly depend upon
      the ovarian reserve. The evaluation of FSH concentration during the first days of
      the menstrual cycle provides a simple and accurate means of assessing ovarian
      reserve. Plasma FSH value is correlated with cancellation rate, peak estradiol,
      number of oocytes retrieved and of the resulting embryos, pregnancy rate, outcome
      of cryopreservation. However, a poor response to the stimulation treatment is
      unpredictable in a subgroup of women whose FSH concentration remain within the
      normal range. Ovarian aging begins several years before any clinical or
      endocrinological modification. Recurrent FSH determinations may help in
      predicting a poor response, as a large intercycle FSH variability is correlated
      with ovarian failure. The value of ovarian reserve tests is presently not fully
      established.

PMID- 8998508
TI  - [Poor responders followed for 3 years in an IVF program].
AB  - Our study consisted of a population of 100 women who represented an insufficient
      response to the induction of ovulation. We researched to find out which
      therapeutic approach, of the subsequent attempts to IVF would give greater hope
      to a better response. Two groups were individualized: in the first group (62
      women) we obtained at least once, 3 oocytes (288 attempts), in the second group
      (38 women) we always obtained less than 3 oocytes. In the first group, in order
      to raise the pregnancy rate it was necessary to raise the rate of E2/oocyte.
      There fore raising the duration of stimulation and the quantity of ampullage of
      hMG. The long protocol, hMG, produced the best results. In the second group, the
      results were always worse it was more than a problem of protocol, it was a
      problem of the patients. In reality, the future of therapy for lower responsive
      patients is probably biological with hatching today and the possibilities with
      oocytary maturation in vitro in the near future.

PMID- 8998509
TI  - [Contribution of Doppler color ultrasonography to the screening and surveillance
      of ovarian hyperstimulation syndrome].
AB  - Color and power Doppler producing ovarian vascular mapping allows to realize a
      new functional approach of ovarian hyperstimulation syndrome (OHS); local
      vascular factors (ovarian angiogenesis, increase in cappillary permeability)
      released by hCG injection (LH effect) have in fact an important part in this
      syndrome. Vaginal Doppler sonography allows: -before induction, to predict
      potential risk of hyperstimulation: polycystic ovaries, spontaneous stromal
      hypervascularization; -in monitoring of ovulation stimulation, to reduce risk of
      multiple pregnancy and to detect early hyperstimulation, decision of hCG
      injection depends on number of follicles able to be fertilized (> 15 mm) and
      luteinized (> 10 mm); -to assess severity of OHS and search complications:
      ascites, hydrothorax, ovarian torsion and deep venous thrombosis. So OHS
      prevention imposes a monitoring by Doppler sonography and estradiol assay of all
      cycles induced by gonadotropins.

PMID- 8998510
TI  - [Ovarian hyperstimulation in medically assisted reproduction: which practical
      approach?].
AB  - Ovarian hyperstimulation syndrome (OHS) with serious grade could be a live
      threatening disease, that occurs in 0.5% to 1% of in vitro fertilization program.
      The prevention of OHS is based on the recognition of risk factors and on
      ultrasonic and hormonal monitoring, with well adapted treatment in order to
      reduce the number of follicles. The level of oestradiol will determine the
      injection of human chorionic gonadotropins: between 2500 and 3000 pg/ml, the
      injection of HCG is reduced to 5000 U for the induction of ovulation, and the
      injections of HCG 1500 during the luteal period are avoided: between 3000 and
      5000 pg/ml, the injection of HCG is reduced to 5000 U and the replacement of
      fresh embryos is deferred to an other cycle: after 5000 pg/ml, the injection of
      HCG must be abandoned. The treatment of the confirmed OHS is based on the rest,
      with hospitalization, correction of fluid, electrolyte and protein imbalance,
      prevention of thrombo embolism and aspiration of ascite fluid.

PMID- 8998511
TI  - [Embryonal metabolism].
AB  - It is very difficult to have a clear and homogeneous idea of the embryo
      metabolism. In fact it may vary from one species to another and also according to
      the embryonic stage: i.e. before and after genomic activation. Basic compounds
      such as glucose may be toxic, but obviously, it is more the problem of the
      quantity introduced in the culture media and an unsuitable balance between the
      metabolites which may impair the embryonic development. At low concentration
      glucose is actively metabolised by embryos. High levels of amino acids are
      deleterious (due to release of ammonia), but they are necessary at low
      concentrations. Addition of serum or other biological fluids is generally
      useless. Further knowledge on embryo metabolism is necessary to avoid culture
      medium related delay or developmental blocks. Sequential media are at least
      partly the answer.

PMID- 8998512
TI  - [Preimplantation assessment: experimental data on animals and humans].
AB  - Assessing and/or improving the implantation prognostic remain a major goal for
      research studies as well as for teams doing embryo transfer in many species.
      Criteria for such a goal were focussed ten years ago and combined theoretically: 
      sensitivity for applying to one embryo; -clear cut-off for individual decision; 
      fastness to be suitable for embryo transfer in due time; -no toxicity or
      invasiveness for embryo; -finally some simple technical approach in order to be
      applies by a large number of teams. Moreover whatever may be qualitative or
      quantitative criteria, they should be relied to the final result as alive
      newborn. The more ancient way to appreciate embryo quality deal with the simple
      observation of morphological and kinetic criteria about embryo, but such non
      invasive approach was obviously limited, in spite of the positive influence of
      regular blastomers, absence of fragmentation and synchronization with time of
      transfer on implantation rate. The major transcriptional activity of human embryo
      developing between 6 and 8 cells stage, of course, were unassessed by transfer to
      day 2. Moreover the apparent quality of the embryo better reflected oocyte
      quality than embryo quality. Coculture development encompassed only partially
      such limitation. Using fluorescent probes, it was possible to evaluate some
      metabolic activity as well as membrane integrity, but such criteria revealed to
      be both invasive and uneasily reliable with developmental ability of the embryo.
      Methods dealing with glucidic, protidic or lipidic metabolisms are developed
      elsewhere, but revealed uneasy to apply, due both to their invasiveness or
      technical difficulties and their large inter-individual variability. Some hope
      has raised by the finding of growth factors or cytokines which are expressed by
      the embryo and/or embryotrophic but a lot of works remain to be down before an
      easy practical application.

PMID- 8998513
TI  - [Value of an embryo score to predict implantation].
AB  - The prognostic value of the score of embryo transfer (SET) was assessed on 1079
      embryo transfers in a homogene population of patients. The SET is obtained adding
      the embryo score (ES) of each transferred embryos. ES is based both on the
      conventional parameters of embryo morphology, and on the 4-cell stage which is
      the optimum division stage regarding implantation. The SET is strongly correlated
      with the pregnancy rate (p < 10-5), and is, with the mean score of transferred
      embryos (MSTE), the most sensitive and specific parameter of all studied
      parameters. However, embryo quality seems not to be correlated with miscarriages.

PMID- 8998514
TI  - [Quality of the conceptus: embryo transfer strategy].
AB  - Embryo transfer is one of the key points of human IVF. Success or failure, as
      well as further incidence of multiple pregnancies are the immediate consequence
      of this technical point. The IVF transferus has also to manage with the patient
      anxiety. The technical points of embryo transfer are reviewed. Results of the
      national french registry concerning transfers of 2 or 3 embryons are also
      analysed. Then, an experience concerning delayed embryo transfer at the
      blastocyst stage is reported, taking in to account the high PR obtained after
      transfer of frozen thawed blastocysts.

PMID- 8998515
TI  - [Vitrification: a cryopreservation method useful for mammal embryos].
AB  - The author first exposes the theoretical concept of vitrification before giving
      the conditions required to formulate the composition of an adequate vitrification
      solution. These conditions are: -the choice of the cryoprotectant (non toxic),
      its concentration, the addition or not of a macromolecule like Ficoll, PVP, to
      facilitate vitrification and/or a sugar like sucrose; -the time and temperature
      of exposure to the vitrification solution as well as the dilution procedure after
      thawing to minimize osmotic and toxic stress. Then he presents in a series of
      tables, a summary of the results of vitrification of oocytes and embryos of
      laboratory and domestic animal species and he mentions some parameters
      influencing the results such as the species, the stage of development, the origin
      of the embryos. He concludes that vitrification seems to be an interesting method
      for cryopreservation of gametes and embryos.

PMID- 8998516
TI  - [Embryo freezing: status survey in France (1985-1993). Federation of BLEFCO].
AB  - The French Federation of IVF Biologists (BLEFCO) reports the first survey on the
      fate of 102812 human embryos frozen in France during a nine-year period (1985
      1993). 94% of surviving embryos were transferred to the parental couple, 6% were
      thawed to conclude their storage while embryon donation remained exceptional
      (0.2%). 55% of all thawed embryos survived the freeze-thaw procedure. However,
      only 3.5% of transferred embryos achieved full-term development (as compared to
      9% for unfrozen embryos). Thus, embryo freezing efficiency remains low but highly
      variable among different centers. Therefore, cryopreservation has led to the
      birth or more than 1200 babies and for several group, has contributed up to 22%
      of IVF deliveries. The variability observed in the results can be largely related
      to the adequacy of programmable freezers. Indeed, 68% of frozen embryos survived
      after thawing in case of manual seeding (15% pregnancy per transfer) versus 42%
      in case of automatic seeding (9% pregnancy per transfer, p < 0,001). Freezing has
      no adverse effect on the rate of anomalies at birth (1.8%).

PMID- 8998517
TI  - [Artificial insemination by donor/in vitro fertilization by donor and quality of
      the embryo. Federation of CECOS].
AB  - OBJECTIVE: To assess pregnancies and conceptus after artificial insemination
      (IAD) or IVF with frozen semen donor (IVFD) on sufficiently large study
      population in order to distinguished minor variations. STUDY DESIGN: From 1987 to
      1994 all pregnancies obtained after AID or IVFD where registered prospectively in
      the French CECOS Federation data base. Different factors were recorded for this
      study: first menarch age of the recipient women, cycle length, insemination date
      in the conception cycle, maternal age at delivery, hormonal treatments, donor
      age, sperm conservation length and follow up of the pregnancy: miscarriage, tubal
      pregnancy, time at delivery, sex of the fetus, weight, malformation. RESULTS:
      21,597 pregnancies obtained after AID and 3381 after IVFD were registered. 2%
      where lost of follow up. Fetal loss rate is 18% after AID and 21.5% after AID and
      1.7% after IVFD (p < 0.0001). 18,128 children were born after AID and 3,313 after
      IVFD. After AID the twin pregnancy rate is 6.9% and the multiple pregnancy (> or
      = 3 fetus) rate is 0.7%. After IVDF these rates are respectively 24.8% and 4.2%
      (p < 0.0001). After AID the mean weight at delivery, sex ratio, premature rate,
      intra uterine growth retardation rate are not different from national rates
      published in 1995. The fetus malformation rate (including medical abortions) is
      1.9% after AID and 2.7% after IVFD (p < 0.009). After AID the trisomy 21 rate
      increase with the mother age but also with the donors age if the maternal age is
      equal. The birth defects rate is not different from those registered in Paris,
      Strasbourg and Marseille. The birth defects rate observed after IVDF is not
      different from the rate observed after IVF with husband semen (2.74% versus
      2.99%, p = 0.16). CONCLUSION: After AID the miscarriage and tubal pregnancy rate,
      the children weight, the premature rate is not different from the general French,
      population. Sex ratio is normal as the global malformation rate. The multiple
      pregnancy rate (x 7 for twin and by 10 for multiple pregnancies more than 3
      fetus) is high showing the influence of ovulation induction treatment. The birth
      chromosomic abnormalities rate is normal and correlated to the mother age but
      also to the donor age. This result without clear biological explanation will
      require further verification in a greater population. Practically speaking, this
      observations encourages lowering the age limit for the semen donors less than 45
      years. IVFD practice instead of AID double the tubal pregnancy rate (0.9% versus
      1.7% and increase the twin pregnancy rate by 2.5% and the multiple pregnancy (>
      or = 3 fetus) rate by 3. It is necessary to promote AID from which the pregnancy
      rate is very different from one center to another with in the centers with AID
      low results a too high rate of IVFD. Finally we can say that pregnancy from IVFD
      or IVF with husband semen are not significantly different. In other words
      pregnancy outcome is not changed after sperm cryopreservation.

PMID- 8998518
TI  - [1995 evaluation of medically-assisted procreation with a donor. French
      Federation of CECOS].
AB  - 1995 results of French Federation of CECOS and IFREARES-Toulouse are recorded. In
      1995 16% less AID demands were registered. 5156 patients (19% less than in 1994)
      underwent procreations with sperm donor during 14209 cycles (AID and IVF D),
      resulting in 1655 pregnancies. 647 volunteers men come forwards as sperm donors.
      The analysis of the 1606 deliveries resulting of 1994 activity show always the
      same percentage of multiple births and malformations. The activity of semen
      preservation is increasing with an higher percentage of cryopreservation,
      consequence of ICSI using.

PMID- 8998519
TI  - [1995 evaluation of the CECOS Federation. Use of different methods of assisted
      reproductive techniques].
AB  - Intracervical insemination IC is still the most common method of ART with frozen
      donor semen. During the year 1995 in France IC was used in 63% of all cycles,
      with a pregnancy rate per cycle (PR) of 9.3%. Intrauterine insemination IU was
      used in 24% of all cycles with a PR of 13% (p < 0.01) and in vitro fertilization
      IVF in 12% of all cycles with a PR of 22% (p < 0.01). The benefit of the
      different methods, in relation with the number of unsuccessful cycles, and in
      relation with the quality of frozen semen is analysed.

PMID- 8998520
TI  - [Oocyte donation -- embryo donation].
AB  - From 1993 to 1995, 82 donors have permitted the retrieval of 810 oocytes allowing
      to obtain 411 embryos. 95 receiving couples have been included : 30 obtained a
      pregnancy, 7 abandoned and 38 are waiting for a transfer. The rate of pregnancies
      by transfer is superior to the one observed with the transfer of frozen embryos
      (40.5% versus 27%).

PMID- 8998521
TI  - [1995 FIVNAT evaluation].
AB  - FIVNAT registry collected information on 31320 individual assisted reproductive
      technology (ART) cycles in 1995, 76.8% being conventional in vitro fertilization
      (IVF) cycles, and 22.2% microinsemination cycles, mainly ICSI. The per recovery
      and per transfer pregnancy rates remained fairly stable, in comparison with 1994
      at respectively 19.0% and 23.8%. There was a slight decrease in the number of
      recovered oocytes (8.4 +/- 5.7 vs 8.6 +/- 5.7), but as the fertilization rate
      increased from 46.3% to 48.6%, the final number of embryos was at the same level.
      The number of transferred embryos was still decreasing (2.59 +/- 0.99 vs 2.65 +/-
      1.06). The take-home-baby rate was nearby 15%. Infertilities involving a tubal
      factor still decreased to 53.5%, and those involving a male factor (with the use
      of husband's or donor's semen) represented almost 50%, but the use of donor's
      semen has decreased, probably because of the development of ICSI. The stimulation
      regimens using GnRH analogues represented 91.9%, 78.9% being with a long blockage
      period. They were associated with the highest per transfer pregnancy rate
      (25.0%). The percentage of transfers with more than 3 embryos decreased from
      18.6% to 14.7% (p < 0.001), indicating that French IVF units are still
      progressing towards a policy the aim of which being to reduce multiple
      pregnancies. The pregnancy rate was at 29.4% for transfers involving 3 embryos.
      Analysis on the IVF outcome concerned all the pregnancies (16423) and newborn
      (16228) from procedures realised between 1986 and 1994. The ectopic rate
      decreased progressively. There was also a recent decrease in the multiple
      pregnancies, even before selective reduction. In 1994, the triplet rate reached
      1.8% and 4%, respectively after and before reduction. Compared to natural
      pregnancies, IVF pregnancies were associated to higher prematurity rate (overall,
      27%, singleton, 9.2%), hypotrophy and perinatal mortality rates. There was no
      evidence of any increase in the malformation rate.

PMID- 8998522
TI  - [FIVNAT evaluation of frozen embryo transfers from 1987 to 1994].
AB  - Between January 1987 and December 1995, 15676 thawed embryo transfers were
      included in the Fivnat register. During this period, the per transfer pregnancy
      rate increased from 11.5% to 16.0%. Medical practice, results and pregnancy
      factors were analysed on 11584 transfers collected until december, 1994. The
      relationship between patients' characteristics or OPU cycles variables and
      pregnancy was analysed on a sub sample of 8483 cycles of frozen embryo transfers
      for which the files could be related to the original cycle which gave rise to the
      frozen embryos. The per transfer pregnancy rate is decreased when the transfer
      cycle combines hormonal substitution and GnRH analogue, or includes Clomiphene
      Citrate in the stimulation regimen. It increases with the number of transferred
      embryos (from 7.3% with 1 embryo to 16.5% with 3, and decreases when the women's
      age increases (3.2% after 41 years). It is higher when GnRH analogues were not
      used in the OPU cycle, and higher with FSH when the long protocol is used. The
      pregnancy rate is also higher when the OPU cycle resulted in a clinical
      pregnancy. Abortion and ectopic pregnancy rates are close to those resulting from
      transfers of fresh embryos. The multiple pregnancy rate is lower as are the
      preterm birth rate and hypotrophy. The malformation rate at birth is close to
      that of fresh embryo transfers after IVF.

PMID- 8998523
TI  - [Evolution of intra-cytoplasm sperm injection activities from 1992 to 1995.
      FIVNAT].
AB  - There was a large increase in the number of ICSI realised in France between 1992
      and 1995, reaching 20% of all the OPU in 1995. Approximatively 95% of all the
      ICSI were realised for male infertility, more than 4% being performed with semen
      from epididymis or vas deferens. Women were slightly younger (32.7 +/- 4.6 years)
      than for conventional IVF, but infertility duration and stimulation regimens were
      the same. The pregnancy rate increased since 1992, reaching 23% in 1995, higher
      than in conventional IVF, and fertilization rate reached the same level (50%).
      The main success factors were women's age, the number of transferred embryos and
      the experience of the biologists attested by its length. The increased pregnancy
      chances associated with a high number of transferred embryos has to be
      considered. There could exist an increase in multiple pregnancies in the next
      future.

PMID- 8998524
TI  - [Ovulation stimulation. FIVNAT].
AB  - In 1995, there was an increased use of GnRH analogs in IVF French programs, there
      was too an increase in the use of FSH (alone or combined with hMG). In general
      population, the best results are always obtained by the use of GnRH analogs in
      long protocols, pure FSH significantly increase the pregnancy rates. In a
      selectioned population (less than 35 years old, 1st IVF attempt and sperm and
      ovulation normal), pregnancy rate remains the best in long protocols, and pure
      FSH always improves the results (significantly in short protocols).

PMID- 8998525
TI  - [Neuro-cognitive sequelae during acute lymphoblastic leukemia in children].

PMID- 8998526
TI  - [How to recognize streptococcal pharyngitis?].

PMID- 8998527
TI  - [Mental prognosis of Apert syndrome].
AB  - BACKGROUND: Mental retardation, considered as common in Apert syndrome could be
      in part due to associated brain abnormalities. POPULATION AND METHODS: Sixty
      patients (32 males, 28 females) were included in the study. Patient age at the
      last examination was over 3 years (mean 10 years, range 3-28 years) in 38
      patients. IQ was assessed from psychometric tests adapted for age. Brain anatomy
      was studied by MRI. Age at operation and quality of familial environment were
      also evaluated. RESULTS: The IQ was over 70 in 12 patients (32%), over 90 in five
      (13%) and the mean IQ was 62 (10-114). Thirty percent of patients had
      abnormalities of the corpus callosum, 43% of the cerebral ventricles and 55% of
      the septum pellucidum. There was no anomaly in 28% of the patients. One or more
      operations were performed in 53 patients, before one year of age in 37. Ten
      children were institutionalized or in deleterious family situation. The main
      factor influencing the mental prognosis was the age at operation: the final IQ
      was over 70 in 50% of the children operated on before one year of age versus 8%
      in those operated on later (P = 0.01). Only the anomalies of the septum
      pellucidum seemed to play a role: 50% of the patients with normal septum had an
      IQ > 70 compared to 18% in those with septum anomalies (P < 0.04). The quality of
      the familial environment also influenced the mental development: 12.5% of the
      patients who were institutionalized or in difficult familial situation had an IQ
      > 70 compared to 39% of those who live in a normal family. CONCLUSIONS: Careful
      investigation including MRI is necessary for detecting associated brain
      abnormalities. The patients must be operated on early, if possible before the age
      of nine months. Attention has also to be paid to quality of the sociofamilial
      environment.

PMID- 8998528
TI  - [Microdeletion of the chromosome 22q11 in children: apropos of a series of 49
      patients].
AB  - Most of the children with Di George syndrome and 60% of patients with
      velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11. The
      phenotypic expression of this chromosomal abnormality is highly variable.
      PATIENTS: Forty-nine children, 0 to 15 years of age, were demonstrated as
      carriers of a 22q11 microdeletion. The main referral diagnoses were: Di George
      syndrome (19 cases), velocardiofacial syndrome (14 cases); congenital heart
      defect with dysmorphism (9 cases); hypoparathyroidism (2 cases). The
      microdeletion was detected by fluorescent in situ hybridization with probes
      specific of the 22q11 region. RESULTS: Facial dysmorphism was the only constant
      feature. A congenital heart defect was present in 84% of cases. Significant
      hypocalcemia was documented in 51% of cases and thymic hypo or agenesis in 83%.
      Significant immune deficiency was documented in nine cases. The most frequent
      associated defects were urinary tract malformations (8 cases). A cleft palate was
      present in height enfants but velopharyngeal insufficiency was almost constant.
      Two-thirds of children had psychomotor delay, and five children exhibited
      behavioral problems. Of the 35 couples of parents tested, eight mothers were
      found to be carriers of the deletion. CONCLUSION: For the pediatrician, it is
      essential to know the variability of the clinical picture. The long-term
      prognosis is conditioned by the possibility of mental retardation and learning
      disabilities. Parents should be tested for the presence of the deletion. The
      occurrence of the microdeletion in asymptomatic relatives raises difficult
      problems in genetic counselling.

PMID- 8998529
TI  - [Survey on the practice of extrarenal hemofiltration in pediatrics].
AB  - BACKGROUND: Several methods of dialysis are currently available. The choice of
      whether to use one of them is determined by multiple factors that are analyzed in
      this study. PATIENTS AND METHODS: One hundred and twenty-six children (mean age:
      48 +/- 6 months) were treated in 29 French intensive care units and/or
      departments of nephrology during 1991. The underlying diseases were: hemolytic
      uremic syndrome (HUS) in 28% of patients, other renal diseases in 6%, metabolic
      diseases in 8%, septic shock in 8%, cardiogenic shock in 9%, hypovolemic shock in
      10%, multiple organ failure in 7%, acute liver disease in 9% and other diseases
      in 15%. RESULTS: Peritoneal dialysis (PD) was the favorite method in patients
      less than 10 years: intermittent hemodialysis (IHD), continuous hemofiltration
      and hemodiafiltration, (HF, HDF) were preferentially used above this age. PD was
      used in 85% of HUS, 58% of shocks and 50% of metabolic diseases. Sixty percent of
      acute renal diseases other than HUS were treated by IHD. HF and HDF were used in
      66% of acute liver diseases and 42% of shocks. Overall mortality was 40% but no
      death could be directly ascribed to the different methods of dialysis.
      CONCLUSION: The choice of method depends on the type of underlying disease, age
      of the patient but also the equipment of centers. Progress in evaluating
      indications and results of the different methods of dialysis are necessary.

PMID- 8998530
TI  - [Trial of prevention of severe Haemophilus influenzae type b infections and trial
      of tolerance, after PRP-T vaccination, in the Val-de-Marne region].
AB  - BACKGROUND: Protein-polysaccharide conjugate H influenzae vaccine is now
      routinely recommended for infants. To assess the vaccine's protective efficacy
      against invasive H influenzae infections and its safety, we conducted a study in
      the Val-de-Marne area of France. METHODS: From April 1991 to April 1993, 22,443
      children less than 5 years of age were given PRP-T vaccine. Infants less than 6
      months were given three doses whereas those between 6 and 12 months received only
      two doses, and children over 1 year of age received one dose. According to the
      infant's DTP-IPV vaccination status, PRP-T was administered alone or
      reconstituted extemporaneously with DTP-IPV. The immunogenicity of the conjugate
      vaccine was assessed after three doses in 100 infants under the age of 6 months.
      RESULTS: The PRP-T vaccine administered alone was safe. The reactions were more
      frequent when PRP-T vaccine was combined with DTP-IPV vaccine but they were
      comparable in frequency and severity to those observed after DTP-IPV vaccination.
      Before 1992, 18 Hib infections were reported each year in the Val-de-Marne
      region. During the study, only three Hib infections were reported each year.
      CONCLUSIONS: The fall in incidence of Hib infections, greater than expected,
      suggests a widespread immune effect of the vaccine, possibly due to a decrease in
      Hib nasopharyngeal carriage. The antibody titres to each component of vaccine
      were comparable to those observed in previous clinical infant studies.

PMID- 8998532
TI  - [Post-traumatic pulmonary pseudocysts].
AB  - BACKGROUND: Pulmonary pseudocyst is an unusual complication of chest trauma. CASE
      REPORT: A 12-year-old boy suffered from a non penetrating chest trauma.
      Examination was normal except mild hemoptysis. Chest X-rays and tomodensitometry
      showed several cystic lesions surrounded by areas of pulmonary contusion in the
      right lower lobe. X-rays performed a few years before the trauma were normal. The
      cystic lesions progressively disappeared within a few months. CONCLUSION: This is
      a new case of post-traumatic pulmonary pseudocyst whose diagnosis may be
      difficult until spontaneous cure.

PMID- 8998531
TI  - [Neonatal diabetes mellitus associated with an autoimmune disease].
AB  - BACKGROUND: Insulin-dependent diabetes mellitus can be associated to an auto
      immune disease. A similar association may be seen in the neonate. CASE REPORT: A
      one-day-old boy was admitted for ketoacidosis due to diabetes mellitus.
      Investigation showed that he also suffered from an auto-immune enteropathy with
      several types of autoantibodies, particularly anti-enterocytes antibodies.
      Immunotherapy was ineffective. Multi-organ lesions developed subsequently,
      particularly a pulmonary disease responsible for the death at the age of 2 years.
      CONCLUSION: Physiopathology of this association remains unclear and the report of
      further cases should help improve our knowledge.

PMID- 8998533
TI  - [Giant cell hepatitis and autoimmune hemolytic anemia: efficacy of splenectomy on
      hemolysis].
AB  - BACKGROUND: The previously reported cases of giant cell hepatitis with autoimmune
      hemolytic anemia were improved by prednisone plus azathioprine. CASE REPORT: A 14
      month-old boy suffered from giant cell hepatitis with auto-immune hemolytic
      anemia and positive direct Coombs test. Prednisone and azathioprine
      administration improved the liver disease but failed to control hemolysis so that
      repeated blood transfusions were necessary. Persistance of severe degree of
      hemolysis required splenectomy that was promptly and definitively effective.
      Azathioprine and prednisone were pursued for a total duration of five years.
      Twelve years after the onset of the disease, the child is well without any
      treatment. CONCLUSION: This is the first reported case of such an association in
      which poorly controlled auto-immune hemolytic anemia benefited from splenectomy.

PMID- 8998535
TI  - [Post-traumatic hypopituitarism after skull injury: apropos of 3 cases].
AB  - BACKGROUND: Hypopituitarism is a rare but well-known complication of cranial
      trauma. In the absence of overt diabetes insipidus, its recognition is difficult
      as the onset of clinical symptoms can be very progressive, up to several years.
      CASE REPORTS: Three children, aged 8, 9 and 2 years, respectively, were admitted
      after a cranial trauma. Manifestations of diabetes insipidus occurred a few days
      later in two patients; one of them developed secondary growth hormone deficiency,
      hypothyroidism and hypogonadism, only evidenced at the age of 14 years. The third
      patient also developed manifestations of hypothalamic and/or pituitary hormone
      deficiencies without diabetes insipidus at the age of 12 years-6 months. MRI
      showed complete severance of the pituitary stalk in two patients and absence of
      posterior pituitary signal in one of the two patients with diabetes insipidus.
      CONCLUSION: Growth disorders and/or hypogonadism may occur many years after a
      trauma that may have been forgetten. Search for such an etiology and dynamic MRI
      are necessary in identifying heterogenous hypophyseal lesions.

PMID- 8998534
TI  - [Early diagnosis and treatment of cytomegalovirus polyradiculoneuritis in a child
      infected by HIV].
AB  - BACKGROUND: Axonal polyradiculopathy due to cytomegalovirus (CMV) in AIDS has
      been reported in adults but it is not well documented in children. OBJECTIVE: We
      describe the elements of diagnosis and the outcome after anti-CMV therapy in a
      pediatric case. CASE REPORT: A 11-year-old boy with post-transfusional AIDS and
      low CD4 count (< 50/mm3) suffered from bilateral leg pain and weakness
      progressing within 15 days to paraplegia and cauda equina syndrome.
      Electromyography showed pure axonal neuropathy. Examination of the CSF showed
      increased proteins, low glucose concentration, neutrophilic pleiocytosis and
      positive detection of CMV by polymerase-chain reaction. The CMV viremia was
      positive. Treatment with ganciclovir and foscarnet allowed dramatical clinical
      improvement. Retinitis occurred during the maintenance therapy and was cured
      after reintroduction of the initial doses of ganciclovir and foscarnet. The child
      died five months later from a bacterial pneumopathy. CONCLUSIONS: Children with
      advanced AIDS may benefit from early recognition and treatment of CMV
      polyradiculopathy. The interactions and cumulated toxicities between anti-CMV and
      anti-retroviral drugs must be considered. The prognosis remains poor for CMV
      neuropathy due to the severe immunodepression caused by the HIV infection.

PMID- 8998536
TI  - [Wilms tumor and Bloom syndrome].
AB  - Bloom syndrome is characterized by growth failure, skin anomalies with sun
      sensitivity, minor anatomic defects, excessive chromosomic fragility and usually
      severe immune deficiency. The chromosome fragility predisposes these children to
      the development of hematologic malignancies and solid tumors. CASE REPORT:
      Morgan, a 4-year-old boy with Bloom syndrome, developed a Wilms tumor.
      Chemotherapy was poorly tolerated. Two years later, the child died from an
      uncontrolled progressive disease. CONCLUSION: This is the fourth reported case of
      Wilms tumor occurring in a child with Bloom syndrome. This possibility requires
      repeated abdominal ultrasonography in such patients.

PMID- 8998537
TI  - [Epistaxis in children].
AB  - Most epistaxis in children come from the anterior part of the nasal septum. The
      bleeding is usually under control by manual compression or vestibular packing
      with a piece of cotton or calcium alginate. In case of severe or recurrent
      epistaxis, one must look for a bleeding disorder or a nasal/nasopharyngeal
      tumour, especially juvenile nasopharyngeal angiofibroma in adolescent males.
      Chemical or electrical cautery of the septum should be suggested in case of
      recurrent idiopathic epistaxis. When bleeding continues despite such treatments,
      anterior nasal packing is recommended; life-threatening epistaxis usually
      requires posterior packing. Embolisation can be used to reduce blood supply
      before surgery in case of haemorragic tumours or vascular malformations.

PMID- 8998538
TI  - [Molecular biology of fragile X syndrome: recent data and diagnostic
      applications].
AB  - Fragile X syndrome is the most common cause of inherited mental retardation.
      Since the identification of the mutation, a Cytosine-Guanine-Guanine repeat in
      the Fragile X Mental Retardation (FMR1) gene, the genetic counselling and the
      diagnosis of the disease have been dramatically improved. The nature of the
      mutation and its size must be integrated in the calculation of the risk of
      transmission of mental retardation and in the genetic counselling in the family.
      Out of 245 patients affected with mental retardation referred to our laboratory,
      we found 37 (15%) fragile X patients, allowing to screen for the mutation in the
      family and to propose prenatal diagnosis in carrier females.

PMID- 8998539
TI  - [Cytokines: new markers in perinatology?].

PMID- 8998540
TI  - [Radiologic case of the month. Spondyloepiphyseal dysplasia tarda].

PMID- 8998541
TI  - [Hemi-megaloncephaly and Klippel-Trenaunay-Weber syndrome].

PMID- 8998542
TI  - [Pulse oximetry and methemoglobinemia].

PMID- 8998544
TI  - [Central catheter in newborn infants: inserted through peripheral vein
      denudation].

PMID- 8998543
TI  - [Aseptic meningitis during treatment with immunoglobulins].

PMID- 8998545
TI  - [Thrombopenia induced by amphotericin B in an extremely premature infant with
      congenital candidiasis].

PMID- 8998546
TI  - [Uveitis after viper bite].

PMID- 8998547
TI  - High-performance liquid chromatographic measurements of urinary hydroxycarboxylic
      acids as an index of the metabolic control in non-insulin-dependent diabetic
      patients.
AB  - Hydroxycarboxylic acids in urine of patients with non-insulin-dependent diabetes
      mellitus and of healthy subjects are analyzed as 2-nitrophenylhydrazides by an
      improved high-performance liquid chromatographic method which has advantages with
      respect to resolution and analysis time. Variations in levels of
      hydroxycarboxylic acids, originated from the metabolism of valine, leucine and
      isoleucine, have been described in the diabetic patients who have good and poor
      metabolic controls. The sum of the hydroxycarboxylic acids in both groups of
      diabetic patients was significantly increased compared with the values of the
      healthy subjects. Statistically significant difference was present between the
      two groups. In the whole group of diabetic patients, the sum of the
      hydroxycarboxylic acids correlated with fasting plasma glucose or hemoglobin A1c
      (r = 0.548, P < 0.01 and r = 0.629, P < 0.01, respectively). These results
      suggest that the relevance of these abnormalities may be used as an index of
      metabolic control in diabetic patients.

PMID- 8998548
TI  - Capillary electrophoresis and supercritical chromatography, complementary and
      alternative techniques for the determination of urinary metabolites of styrene.
AB  - Two analytical methods without an extraction step were developed using capillary
      electrophoresis and supercritical fluid chromatography in order to determine
      phenylglyoxylic (PGA) and mandelic (MA) acids in urine, with minimum treatment
      and manipulation of biological samples. The urine was diluted ten-fold in
      acetonitrile and directly injected into the analytical systems after
      centrifugation. Analysis was performed by capillary electrophoresis on alkyl
      bonded phase capillary columns with sodium formiate (4 x 10(-2) M)-isopropanol
      (9:1, v/v) as a buffer, and by supercritical fluid chromatography on a Diol
      bonded phase silica column with ethanol-water-methanesulphonic acid
      (97.5:2.4:0.1, v/v) as coeluent of CO2. Detection of PGA and MA was performed by
      ultraviolet detection at 255 and 210 nm, respectively. The methods are in
      agreement, and are easily able to detect 5 mg/g creatinine for PGA, and 15 mg/g
      creatinine for MA, which are one twentieth of the lowest biological exposure
      index values.

PMID- 8998549
TI  - Determination of dihydroetorphine in biological fluids by gas chromatography-mass
      spectrometry using selected-ion monitoring.
AB  - A method for the determination of dihydroetorphine hydrochloride, a powerful
      anaesthetic and analgesic drug, in biological fluids by GC-MS with selected-ion
      monitoring using etorphine as internal standard was established. Dihydroetorphine
      was extracted from human blood and urine with dichloromethane and then
      derivatized with N-heptafluorobutyrylimidazole after concentration to dryness. A
      dihydroetorphine monoheptafluorobutyl derivative was formed which showed good
      behavior on GC-MS with electronic-impact ionization. The main fragment, m/z 522,
      which is the base peak, was selected as the ion for quantitation and the
      corresponding ion, m/z 520, was selected for monitoring the internal standard,
      etorphine. The recoveries and coefficients of variation of the whole procedure
      were determined with five controlled dihydroetorphine-free urine and plasma
      samples spiked with different concentrations of dihydroetorphine. The
      concentration of dihydroetorphine for quantitation was in the range 1-20 ng/ml
      for urine and 2.5-250 ng/ml for plasma. The correlation coefficients of the
      standard curves are sufficient to determine the dihydroetorphine. The accuracy
      for quantitation of dihydroetorphine in urine and plasma is less than 10.6%.

PMID- 8998550
TI  - High-performance liquid chromatographic determination of cytosine-containing
      compounds by precolumn fluorescence derivatization with phenacyl bromide:
      application to antiviral nucleosides and nucleotides.
AB  - A novel precolumn derivatization method for the HPLC determination of cytosine
      containing compounds by HPLC is described. Highly fluorescent 2-phenyl-3,N4
      ethenocytosine derivatives are produced by a reaction of non-fluorescent cytosine
      containing compounds with phenacyl bromide in weakly acidic acetonitrile solution
      at elevated temperature. The applicability of the method to various biogenic and
      antiviral compounds is demonstrated. Quantitative determination of cidofovir, a
      potent antiviral drug currently undergoing evaluation in the clinic for treatment
      of cytomegalovirus retinitis is also reported. The limit of detection for
      cidofovir in cynomolgus monkey plasma was 5 ng/ml (ca. 100 fmol on column) with
      the between-day precision of 16.6, 6.4 and 2.4% for five replicate samples at 20,
      160 and 320 ng/ml, respectively. The within-day precision was 15.9, 5.9 and 2.1%,
      respectively. The method described has broad applicability and may offer
      significant advantages over existing HPLC methods in antiviral drug development
      as well as in nucleic acid research.

PMID- 8998551
TI  - Determination of penicillin-V in human plasma by high-performance liquid
      chromatography and solid-phase extraction.
AB  - A high-performance liquid chromatographic method has been developed for the
      determination of penicillin-V concentrations between 0.1 and 19 micrograms/ml in
      human plasma. Penicillin-V was isolated from plasma by solid-phase extraction on
      a C18/OH cartridge. The extracts were injected onto a reversed-phase HPLC system.
      A 125 x 4 mm C18 column was used to separate penicillin-V from its main
      metabolites, 5R- and 5S-penicilloic acid and endogenous compounds. The eluent
      consisted of 66% 0.02 M phosphoric acid buffer, to which tetrabutylammonium
      dihydrogenphosphate and 34% acetonitrile were added. The column effluent was
      monitored by ultraviolet spectrophotometry at 269 nm. Using this method,
      penicillin-V concentrations in plasma could be determined with an accuracy
      between -5.4 and 5.2% and a precision between 0.8 and 1.6%. The method has proved
      to be reliable and was used in bioavailability studies for the development of a
      new oral penicillin-V formulation.

PMID- 8998552
TI  - Analysis of L-[methyl-11C]methionine and metabolites in human plasma by an
      automated solid-phase extraction and a high-performance liquid chromatographic
      procedure.
AB  - A fully automated method for separation of L-[methyl-11C]Methionine from
      metabolites in patient plasma was developed. L-[methyl-11C]Methionine was
      isolated from plasma by solid-phase extraction (SPE). The radioactivity retained
      on the SPE column was eluted and injected onto the HPLC system for separation of
      in vivo formed L-[methyl-11C]methionine radiolabeled metabolites. The yield
      through the isolation procedure and HPLC analysis was greater than 95% with a
      precision better than 5% (R.S.D.). The calculated rate of L-[methyl
      11C]methionine transport into tumor tissue was markedly different with and
      without compensation for radiolabeled metabolites in patient plasma.

PMID- 8998553
TI  - On-line metal chelate affinity chromatography clean-up for the high-performance
      liquid chromatographic determination of tetracycline antibiotics in animal
      tissues.
AB  - An on-line high-performance liquid chromatographic (HPLC) method for the
      determination of tetracycline, oxytetracycline, chlortetracycline and
      demeclocycline using metal chelate affinity chromatography-reversed-phase HPLC
      has been developed. The drugs were extracted with succinate buffer and the
      extract diluted with EDTA-pentanesulphonate buffer. Diluted extract was then
      absorbed onto a C8 or XAD-2 solid-phase extraction (SPE) cartridge and eluted
      with methanol. The eluate was then injected onto a TSKgel chelate column which
      had been preloaded with copper(II). The tetracyclines were eluted from this
      column onto the analytical column (Polymer Labs. PLRP-S) with an EDTA-containing
      buffer. Elution of the analytical column was via a methanol-acetonitrile gradient
      and detection was by UV at 350 nm. Average recoveries at the 10, 20, 50 and 300
      micrograms kg-1 levels were 50-80%. The limit of detection (LOD) was 10
      micrograms kg-1 for oxytetracycline and tetracycline and 20 micrograms kg-1 for
      chlortetracycline and demeclocycline. The method was validated for sheep liver
      and cattle kidney.

PMID- 8998554
TI  - Simultaneous determination of azathioprine and 6-mercaptopurine by high
      performance liquid chromatography.
AB  - A specific, sensitive, single-step solid-phase extraction and reversed-phase high
      performance liquid chromatographic method for the simultaneous determination of
      plasma 6-mercaptopurine and azathioprine concentrations is reported. Following
      solid-phase extraction, analytes are separated on a C18 column with mobile phase
      consisting of 0.8% acetonitrile in 1 mM triethylamine, pH 3.2, run on a gradient
      system. Quantitation limits were 5 ng/ml and 2 ng/ml for azathioprine and 6
      mercaptopurine, respectively. Peak heights correlated linearly to known extracted
      standards for 6-mercaptopurine and azathioprine (r = 0.999) over a range of 2-200
      ng/ml. No chromatographic interferences were detected.

PMID- 8998555
TI  - Fluorimetric determination of nicorandil in human plasma by a high-performance
      liquid chromatographic-postcolumn ultraviolet irradiation [corrected] system
      equipped with on-line back-pressure tubing.
AB  - For the determination of nicorandil in plasma, a fluorometric technique using
      HPLC-postcolumn UV radiation [corrected] has been developed. The chromatographic
      system consisted of a single pump, photoreactor and on-line back-pressure tubing.
      The system was suitable for the separation of nicorandil under the present
      reaction conditions. The calibration graph was linear over the range 6.5-1170 ng
      ml-1 using an injected volume of 100 microliters. The pretreatment of the plasma
      samples consisted only of deproteinizing steps by adding perchloric acid. The
      mean recovery from plasma was 90.2%.

PMID- 8998556
TI  - Determination of timiperone in rat plasma by high-performance liquid
      chromatography with electrochemical detection.
AB  - We report a sensitive new method for the determination of timiperone in rat
      plasma by using high-performance liquid chromatography with electrochemical
      detection. The method involves extraction of plasma samples with heptane-isoamyl
      alcohol at pH > 8, followed by back-extraction into dilute acetic acid.
      Separation was accomplished by reversed-phase high-performance liquid
      chromatography on an ODS column with the mobile phase consisting of 0.1 M
      phosphate buffer (pH 3.5)-acetonitrile-methanol (65:20:15, v/v). Recovery was
      greater than 80%. Calibration curve was linear over the concentration range 0.5
      50.0 ng/ml. The limit of quantitation of timiperone was 0.5 ng/ml plasma.

PMID- 8998557
TI  - High-performance liquid chromatographic analysis of (S)-alpha-amino-5
      phosphonomethyl[1,1'-biphenyl]-3-propanoic acid (EAB 515) in brain and blood
      microdialysate (on-line) and in plasma ultrafiltrate of freely moving rats.
AB  - (S)-alpha-Amino-5-phosphonomethyl[1,1'-biphenyl]-3-propanoic acid (EAB 515, I), a
      competitive antagonist of the N-methyl-D-aspartate receptor, has significant
      pharmacological activity in the central nervous system (CNS). An extremely
      sensitive and selective analytical method was developed for the simultaneous
      analysis of I and its hydroxylated analog (RDC, II) in the microdialysate (MD)
      and plasma ultrafiltrate (UF) of rats. Microdialysis was used for in vivo
      sampling of unbound drug in the CSF, cortical extracellular fluid and in the
      blood of freely moving rats. Compound II was used for retrodialysis-based in vivo
      calibration of microdialysis probes to estimate the recovery of I. Compound I,
      being extremely hydrophilic with a high degree of ionization at the physiological
      pH of 7.4, has limited access to the brain regions. This, combined with its low
      microdialysis recovery, made the estimation of low brain concentrations of I a
      challenge. The analytes in MD and UF were separated (within 5 min) by reversed
      phase HPLC on a 250 x 4.6 mm I.D. Maxsil 5 microns RP-2 column, and fluorescence
      of the eluent was monitored at 255 nm (lambda ex) and 320 nm (lambda em). A 0.09%
      (v/v) aqueous solution of trifluoroacetic acid (1 ml/min) was used as the mobile
      phase. The response for I in MD and UF samples was linear from 5 to 2000 ng/ml
      and from 20 to 10,000 ng/ml, respectively. The between-run (n = 6) and within-run
      (n = 3) variability of the assay was < 15%. Plasma-protein binding of I (fu =
      0.68) was determined to be linear from 0.1 to 10 micrograms/ml. The analytical
      sensitivity, precision and accuracy of this method was suitable for the
      characterization of the pharmacokinetics and the CNS distribution of I, following
      administration of intravenous (i.v.) infusion, single i.v. bolus and multiple
      i.v. bolus doses of I to freely moving rats, with continuous microdialysate
      sampling of multiple tissues and simultaneous on-line HPLC analysis.
      Pharmacokinetic parameters for I, as determined from concentrations in blood MD
      samples with on-line analysis, were in good agreement with those estimated from
      concentrations in the UF of plasma samples obtained by conventional sampling.

PMID- 8998558
TI  - Routine determination of flumequine in kidney tissue of pig using automated
      liquid chromatography.
AB  - A high-performance liquid chromatographic assay is described as a routine
      analytical method for the determination of flumequine (FLU) and its hydroxylated
      metabolite (OH-FLU) in pig kidney tissue. Kidney samples (2 g) containing FLU and
      OH-FLU were extracted by liquid-liquid extraction with ethyl acetate (10 ml).
      Analytical separations were performed by reversed-phase HPLC with fluorometric
      detection at 252 nm excitation and 356 nm emission under gradient conditions. The
      mobile phase was acetonitrile-2.7.10(-3) M oxalic acid in water (pH 2.5). The
      assay is specific and reproducible within the flumequine range of 0.050-2.5
      micrograms/g and recovery at 0.050 microgram/g was 94.8%.

PMID- 8998560
TI  - Gas chromatographic determination of eugenol in ethanol extract of cloves.
AB  - An ethanolic extract of cloves was analyzed by gas chromatography directly to
      identify eugenol and other major phenolic compounds without previous separation
      of other components. Separation was performed on a fused-silica capillary column
      of 30 m x 0.53 mm I.D., 0.53 microns film thickness. The detector was a flame
      ionization detector. Helium gas at a flow-rate of 3 ml/min was used as a carrier
      gas. The analysis were performed with linear temperature programming. Nine
      components were detected and special attention was given to the major phenolic
      compound, eugenol.

PMID- 8998559
TI  - Determination of mitoxantrone in mouse whole blood and different tissues by high
      performance liquid chromatography.
AB  - A high-performance liquid chromatographic (HPLC) method was developed for the
      specific determination of mitoxantrone (MTO) in whole blood and different tissues
      of mice (liver, heart, spleen, kidneys). MTO was extracted into dichloromethane
      with ametantrone (AMT) as internal standard. The different tissues were
      homogenised in citrate buffer (pH 3.0) containing 20% ascorbic acid. Separation
      of MTO and AMT was carried out using a Nucleosil C18 column. The mobile phase
      consisted of acetonitrile (33%) and 0.16 M ammonium formate buffer, pH 2.7. UV
      detection was used at 658 nm. Baseline separation of AMT and MTO was achieved in
      all matrices. The calibration curves were linear in all matrices (r > 0.999) in
      the concentration range of 2-200 micrograms/l for whole blood and 2-700
      micrograms/l for tissue homogenates, respectively. The within-day and between-day
      precision studies showed good reproducibility with coefficients of variation
      below 4.5% for whole blood and below 10% for tissue homogenates, respectively.
      The extraction efficiencies of MTO are 60% in whole blood and 38% in tissue
      homogenates. The method described is suitable for pharmacokinetic studies on the
      distribution of MTO in different tissues of mice.

PMID- 8998561
TI  - Rapid, sensitive and direct chiral high-performance liquid chromatographic method
      for ketoprofen enantiomers.
AB  - The stereospecific HPLC assays reported for ketoprofen (KT) mainly utilize
      indirect approaches. These assays involve the formation of amide diastereomeric
      derivatives, which are then separated by chromatography. The advantages of
      indirect methods include versatility, good sensitivity and cost effectiveness;
      however, lengthy preparation time is often required. Therefore, we have developed
      a new direct stereospecific HPLC assay for KT enantiomers to improve preparation
      time and sensitivity. The KT enantiomers and indomethacin, internal standard
      (I.S.), were resolved using a Chiralpac AD column attached to 5 cm Supelcosil LC
      SI at constant temperature (30 degrees C). The mobile phase consisted of hexane
      isopropanol-trifluoroacetic acid (90:10:0.1). Under chromatographic conditions
      employed R-KT, S-KT and I.S. were eluted at 12, 14 and 16 min, respectively. A
      linear concentration response relationship was found (0.05-5.0 micrograms/ml of
      enantiomers) which covered normally observed concentrations in plasma after
      conventional doses of KT. The minimum quantifiable concentration of the assay was
      found to be 0.025 or 0.25 microgram/ml based on 1 ml of human or 0.1 ml of rat
      plasma samples, respectively. This direct HPLC method is suitable for
      pharmacokinetic studies of KT enantiomers and offers the advantages of shorter
      sample preparation and run time. This method is at least as sensitive as assays
      currently in use.

PMID- 8998562
TI  - Determination of naloxone in human plasma by high-performance liquid
      chromatography with coulometric detection.
AB  - Naloxone, the analyte and the internal standard, sumatriptan, are extracted from
      plasma using solid-phase extraction columns. Chromatography and detection are
      performed using isocratic reversed-phase high-performance liquid chromatography
      (HPLC) with coulometric end-point detection. The standard curve was linear over
      the range 0-50 ng/ml of naloxone in plasma. The reproducibility, the coefficient
      of variation (C.V.) of the method over the range of the standard curve was 6.2
      11.2%. The recovery averaged 90.4 +/- 8.9%. A plasma profile following i.v.
      administration of naloxone in one normal healthy volunteer is presented.

PMID- 8998564
TI  - Diazomethane as a highly selective fatty acid methylating reagent for use in gas
      chromatographic analysis.

PMID- 8998563
TI  - Determination of the 8-methyl ether of xanthurenic acid in human serum by high
      performance liquid chromatography with fluorescence detection.
AB  - We developed a simple and sensitive assay for the 8-methyl ether of xanthurenic
      acid in serum by high-performance liquid chromatography with fluorescence
      detection (excitation at 340 nm, emission at 450 nm). The compound under study in
      serum samples was extracted with Sep-Pak C18 cartridge and the extract was
      applied to an octadecylsilane-bonded column (Nucleosil 5C18, 150 x 4 mm I.D.).
      The mobile phase used was a mixture of 0.05 M sodium acetate buffer (pH 6.0),
      containing 5 mM sodium 1-octanesulfonate and 0.1 mM Na2EDTA, and acetonitrile
      (93:7, v/v). The 8-methyl ether of xanthurenic acid from serum samples was
      sufficiently separated to be clearly distinguishable. The quantification limit
      was 2 x 10(-14) mol, which was sensitive enough to detect 8-methyl ether of
      xanthurenic acid in serum from normal subjects. The method was applied to samples
      from patients with deficiency in tryptophan metabolism, xanthurenic acid/3
      hydroxy kynurenineuria and showed a striking elevation in serum 8-methyl ether of
      xanthurenic acid.

PMID- 8998565
TI  - Labeling of insulin with non-radioactive 127I and application to incorporation of
      radioactive 125I for use in receptor-binding experiments by high-performance
      liquid chromatography.
AB  - Conditions for the labeling of insulin with radioactive iodine isotopes were
      investigated by means of incorporation of non-radioactive 127I into the peptide.
      Either the chloramine-T (CT) or lactoperoxidase-hydrogen peroxide (LPO) technique
      was applied and reversed-phase high-performance liquid chromatography (RP-HPLC)
      was used for analysis of the reaction products. The LPO method provided the 127I
      labeled peptide within 15-30 min, whereas the CT alternative yielded the labeled
      substrate even within 15 s. However, the latter reaction can only be controlled
      in a reproducible manner with difficulty and undesired side-reactions became
      increasingly prominent when the reaction time of 15 s was exceeded for only a few
      seconds. In another experiment, the LPO technique was applied for radiolabeling
      insulin with 125I. The product was first purified by size-exclusion
      chromatography (SEC) and then subjected to RP-HPLC. SEC yielded two peaks. The
      smaller one, which eluted at a slightly higher Kd value (accounting for about 14%
      of total radioactivity) predominantly consisted of material eluting at the
      column's void volume under the conditions of RP-HPLC, whereas the main SEC
      fraction (accounting for about 86% of total radioactivity) yielded a single peak,
      as shown by HPLC. The radioactive material attributable to the main SEC fraction
      revealed the expected receptor-binding properties, as evidenced by displacement
      experiments with non-radioactive insulin, as well as the action of tetradecanoyl
      phorbol acetate on the binding characteristics and thus indicating formation of a
      labeled hormone retaining biological activity.

PMID- 8998566
TI  - Analytical strategies for the screening of veterinary drugs and their residues in
      edible products (review), by Aerts et al.: an addendum.

PMID- 8998567
TI  - Synthesis and application of boronic acid-immobilized porous polymer particles: a
      novel packing for high-performance liquid affinity chromatography.
AB  - A preparation method of a novel type of packing materials for high-performance
      liquid affinity chromatography to determine glycated proteins was studied, and a
      fundamental study on its application to diabetic serum was conducted. To quantify
      glycated proteins such as glycated serum albumin, a new hydrophilic and durable
      porous polymer particle recently developed in our laboratory was used as the
      basic matrix. The matrix was activated with 1,1'-carbonyldiimidazole (CDI), and
      optimization of the coupling reaction between these CDI-activated matrix and m
      aminophenylboronic acid hemisulfate (APBA) as affinity ligand was investigated.
      The optimum value for the APBA coupling yield was found to be obtained under
      acidic conditions very different from the data reported by previous workers.
      Using this APBA-immobilized matrix an affinity column was prepared, and its
      usefulness in HPLC separation of glycated serum proteins was investigated. Also,
      the fundamental and preliminary results for diagnosis of diabetes mellitus are
      discussed in this paper.

PMID- 8998568
TI  - High-performance liquid chromatographic determination of lipoamidase (lipoyl-X
      hydrolase) activity with a novel substrate, lipoyl-6-aminoquinoline.
AB  - An HPLC lipoamidase (lipoyl-X hydrolase) assay method has been developed, which
      uses a novel fluorescent substrate, lipoyl-6-aminoquinoline (LAQ). LAQ is
      synthesized from lipoic acid and 6-aminoquinoline (AQ) through lipoyl chloride as
      an intermediate and is conveniently purified by washing with chloroform-methanol.
      Mechanistic studies on the time-course, the dependence on enzyme and substrate
      concentrations were performed by using LAQ and a model enzyme (milk lipoamidase).
      Moreover, this method was successfully applied to the direct determination of the
      lipoamidase (LAQ hydrolase) activity in samples of human liver, milk, stools and
      porcine serum. Using this novel synthetic lipoyl substrate, we demonstrated that
      LAQ hydrolase was present in some specific tissues; LAQ hydrolase was solely
      present in the grey matter and not in the white matter in the human cerebrum.
      Furthermore, LAQ hydrolase activity was shown to increase in human liver cancer.
      Thus, this enzyme assay method is expected to be applicable to the tissue
      distribution study and also to the basic research on human diseases such as
      cancer.

PMID- 8998569
TI  - Indirect ultraviolet detection of biologically relevant organic acids by
      capillary electrophoresis.
AB  - Indirect UV detection of fourteen short-chain organic acids (e.g., oxalic acid,
      citric acid, malonic acid, tartaric acid, methylmalonic acid, alpha-ketoglutaric
      acid, succinic acid, ethylmalonic acid, methylsuccinic acid, glutaric acid,
      apidic acid, methylglutaric acid, lactic acid and pyruvic acid) by capillary
      electrophoresis is described. The method used phthalate as the UV-absorbing
      additive in carbonate buffer and the non-absorbing analytes were detected
      indirectly at 230 nm. The influences of buffer pH, ionic strength, concentration
      of phthalate and organic modifier on indirect signal response and migration
      behavior of the organic acids were investigated. Comparisons of reproducibility
      on migration time, limit of detection and separation efficiency among three types
      of capillary (e.g., polyacrylamide-coated, myristyltrimethylammonium bromide
      coated and uncoated capillaries) were conducted. The method developed was applied
      to detect succinic acid, methylmalonic acid, citric acid, glutaric acid and
      lactic acid in human body fluids, and preliminary results were provided.

PMID- 8998570
TI  - One-step purification of rat heart-type fatty acid-binding protein expressed in
      Escherichia coli.
AB  - Heart-type fatty acid-binding protein (H-FABP) is a member of a family of 14-15
      kDa lipid binding proteins which are believed to enhance intracellular transport
      of lipids by facilitating their cytoplasmic diffusion. To obtain sufficient
      amounts of protein for in vitro studies, we expressed rat H-FABP in Escherichia
      coli and compared its biochemical properties with the protein isolated from rat
      heart. An effective method was developed to purify recombinant rat H-FABP from
      cell lysates in a single step using anion-exchange chromatography. This method
      also proved to be applicable for purifying heterologously expressed human H-FABP.
      Recombinant rat H-FABP, which made up approximately 25% of the soluble proteins
      in E. coli, was obtained in a yield of 30-40 mg/l culture. Characterization
      showed that recombinant rat H-FABP was indistinguishable from the protein
      isolated from rat heart regarding molecular mass and oleic acid binding. Some
      heterogeneity upon isoelectric focusing was observed, presumably due to
      differences in N-terminal processing of the proteins. In conclusion, a method is
      presented for efficient high-yield production of recombinant rat H-FABP.

PMID- 8998571
TI  - Determination of amphetamine and related compounds in urine using on-line
      derivatization in octadecyl silica columns with 9-fluorenylmethyl chloroformate
      and liquid chromatography.
AB  - A method for the determination of amphetamine and related compounds in urine
      based on on-line derivatization with 9-fluorenylmethyl chloroformate (FMOC) and
      high-performance liquid chromatography is described. Derivatization is performed
      in a 20 x 2.1 mm I.D. column packed with a Hypersil ODS C18, 30 micron stationary
      phase, which is also used for sample clean-up and enrichment of the analytes.
      Next, the derivatized analytes are transferred to a LiChrospher 100 RP-C18 (5
      micron, 125 x 4 mm I.D.) analytical column for their separation and
      quantification, using reversed-phase conditions and fluorescence detection. The
      described assay was applied to the determination of norephedrine, ephedrine,
      pseudoephedrine, amphetamine, phenylpropylamine and methamphetamine at
      concentrations of 0.5-10.0 micrograms/ml. Analyte conversions were about 55-96%
      of those obtained by the off-line derivatization mode under similar conditions,
      resulting in limits of detection in the 5-25 ng/ml range.

PMID- 8998572
TI  - Reversed-phase high-performance liquid chromatography method for the analysis of
      nitro-arginine in rat plasma and urine.
AB  - Nitro-L-arginine (L-NNA) is an inhibitor of the enzyme nitric oxide synthase
      (NOS). We developed a simple, sensitive and reproducible reversed-phase high
      performance liquid chromatographic method for detection of nitro-arginine (L- and
      D-enantiomer) in rat plasma and urine. Samples were treated with perchloric acid,
      neutralized and eluted through a C8 reversed-phase column with a mobile phase of
      18.5 mM heptanesulfonic acid-10% methanol in water, using theophylline as an
      internal standard. Plasma recovery for both isomers was complete, and the
      sensitivity limit was 0.5 micrograms/ml. This method may be used for disposition
      studies of L-NNA in small animals.

PMID- 8998573
TI  - Determination of delta 9-tetrahydrocannabinol levels in brain tissue using high
      performance liquid chromatography with electrochemical detection.
AB  - delta 9-Tetrahydrocannabinol (delta 9-THC) is the major psychoactive component of
      cannabis. To assist in investigating the mechanism(s) of action of delta 9-THC, a
      convenient method for determining its levels in brain tissue is required. We now
      describe a method for determining nanogram quantities of delta 9-THC in rat brain
      tissue. The method employs solvent extraction with methanol-hexane-ethyl acetate,
      followed by analysis using liquid chromatography with electrochemical detection.
      Overall recoveries were greater than 80%. The relationship between the peak
      height ratio for processed standards extracted in the presence of tissue (delta 9
      THC/internal standard) and the amount of delta 9-THC added was shown to be linear
      within the range of concentrations examined. Quantitative measurements of delta 9
      THC in different brain regions following the intravenous administration of delta
      9-THC are presented as examples of the applications of this method.

PMID- 8998574
TI  - Synthesis of 2-thiothiazolidine-4-carboxylic acid and its chromatography in rat
      and human urine.
AB  - 2-Thiothiazolidine-4-carboxylic acid (TTCA), the urinary biological monitoring
      marker for carbon disulfide in humans was synthesized by reacting carbon
      disulfide with L-cystine. Validation of TTCA purity required elemental as well as
      mass spectral and chromatographic analyses. Two reversed-phase high-performance
      liquid chromatographic columns in series were necessary to resolve picomole
      amounts of TTCA from rat and human urine background peaks on detection at 272 nm
      even after prior diethyl ether extraction from acidified urines in the presence
      of saturated sodium chloride. The isolation procedure for TTCA from urine had a
      recovery of 94.0 +/- 8.1% in the linear 1.1-330 microM concentration range
      (0.0165-4.95 nmol injected mass) with a coefficient of variation of 8.6%. The
      detection limit was about 100 nM (1.5 pmol injected mass).

PMID- 8998576
TI  - Proceedings of the 9th International Conference on Partitioning in Aqueous Two
      Phase Systems. Advances in the use of polymers in cell biology, biotechnology and
      environmental sciences. Zaragoza, Spain, June 4-9, 1995.

PMID- 8998577
TI  - Mental assessment: do you know what day it is?

PMID- 8998575
TI  - Improved high-performance liquid chromatography analysis of 32P-postlabeled 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-DNA adducts using in-line precolumn
      purification.
AB  - An improved HPLC-based 32P-postlabeling assay has been developed for the analysis
      of DNA modified with the food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP). Postlabeled samples are loaded onto a C18 precolumn and
      adducted bases are retained while excess radioactivity and unmodified DNA bases
      are eluted directly to waste through a switching valve. The use of this HPLC in
      line precolumn purification (HIPP) technique allows entire postlabeled samples to
      be analyzed without prior removal of inorganic phosphate and unmodified DNA
      bases. The method has a sample to sample precision of 15% and accuracy of 20%, at
      adduct levels of 2 adducts/10(7) bases and shows a linear relationship between
      signal and adduction levels from 1 adduct per 10(4) to approximately 2 +/- 1
      adducts per 10(9) bases. Individual postlabeled DNA samples can be analyzed by
      HPLC in less than 1 h, allowing high throughput. The use of calf-thymus DNA (CT
      DNA), highly modified with PhIP, or DNA isolated from mice chronically fed a PhIP
      modified diet shows two major PhIP-DNA adduct peaks and three additional minor
      adduct peaks when labeled under ATP-limiting conditions. Isolation of the HPLC
      purified peaks and analysis by thin layer chromatography (TLC) matches the five
      HPLC peaks to the spots typically seen by TLC, including N-(deoxyguanosin-8-yl)-2
      amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (dG-C8-PhIP). Variations in
      digestion techniques indicate a potential resistance of the PhIP-DNA adducts to
      the standard enzymatic digestion methods. Attempts at adduct intensification by
      solid phase extraction, nuclease P1 enrichment or 1-butanol extraction decreased
      PhIP-DNA adduct peaks and introduced a large early eluting peak. Removal of the
      3'-phosphate with nuclease P1 following the kinase labeling reaction simplifies
      the HPLC profile to one major peak (dG-C8-PhIP monophosphate) with several minor
      peaks. In addition to the high resolution provided by HPLC separation of the PhIP
      DNA adducts, this method can be adjusted for analysis of other DNA adducts and is
      readily automated for high throughput.

PMID- 8998578
TI  - Who knows where they go? Quality of life after intensive care.

PMID- 8998579
TI  - The Gaza Strip: an ICU challenge.

PMID- 8998580
TI  - Renal transplantation in a patient with ankylosing spondylitis.

PMID- 8998581
TI  - [The development of perinatology centers in the professional and organizational
      system of maternal and child care].
AB  - The author analyzes the delay in historical development as regards establishment
      of perinatological centres in the Czech Republic, as compared with other advanced
      countries, the task of these centres being specialized care of women with the
      most serious pathological conditions during pregnancy, with premature labour
      before the 32nd week, and care of there newborn babies. By means of three
      internationally recognized criteria which evaluate the quality of this care
      marked improvement of care of these women and neonates was found in 12 officially
      established centres in the Czech Republic, as compared with other maternity
      hospitals. This contributed in a major way to the nationwide reduction of the
      perinatal mortality. At the same time considerable differences were found in the
      results of this care between different centres and also inadequate centralization
      of women with the mentioned complications into perinatological centres. The
      revealed shortcomings will stimulate provisions for the improvement of perinatal
      care in the Czech Republic.

PMID- 8998582
TI  - [Hospitalization during pregnancy--the professional versus the economic
      viewpoint].
AB  - The high percentage of hospitalized pregnant women in the Czech Republic was
      analyzed form the cost benefit aspect within the framework of the current
      transformation of the health services which restricts in-patient care in favour
      of ambulatory care, as part of the developing market economy. Two internationally
      accepted indicators of quality of perinatal morbidity-maternal (rate of
      eclampsia) as well as neonatal (rate of low birth weight infants), i.e. partially
      preventable prenatal hospitalizations. In a comparative epidemiological study the
      incidence of these indicators in the Czech Republic was compared with the
      incidence in Hessen where there is a lower rate of prenatal hospital admissions,
      while there is a similar system of perinatal care and general perinatal
      mortality. In the Czech Republic where the cost of hospitalization of pregnant
      women is higher, the authors found as regards the benefit a lower incidence of
      the mentioned two indicators and from the economic aspect a lower cost of
      neonatal intensive care than in Hessen. This saving was fourfold as compared with
      the higher costs of prenatal hospitalization.

PMID- 8998583
TI  - [Intrauterine growth retardation of the fetus and the pregnancy].
AB  - IUGR (intrauterine growth retardation) is a serious complication of pregnancy.
      The author compared in the submitted paper different diagnostic and therapeutic
      possibilities in a six-year retrospective group of 181 hypotrophic foetuses.
      Based on the results he emphasizes the necessity of magnesiotherapy and
      prevention of IUGR by acylpyrin. It is impossible to monitor and treat adequately
      a pregnant woman with a hypotrophic foetus without Doppler sonography.
      Combination of indexes from various areas (brain, umbilicus) is useful. Even the
      somewhat obsolete method of assessment of estriol in the urine of pregnant women
      should not be refuted. Even during the present period of transformation of health
      services IUGR therapy under ambulatory conditions is not recommended. The author
      emphasizes the comprehensive character of evaluation of all diagnostic methods
      for the detection of IUGR.

PMID- 8998584
TI  - [Preinduction priming of the cervix. Comparison of the intracervical
      administration of PGE2 gel and vaginal administration of estradiol].
AB  - During the period between Jan.1, 1994 and May 31, 1996 at the Second Department
      of Gynaecology and Obstetrics in Brno preinduction was performed in 40 patients
      by means of PGE2 gel (Prepidil Upjohn) and in 38 patients by means of an
      estradiol gel (Biotika). The inclusion criteria in the group were: singleton
      pregnancy, 38 or more weeks of gestation, cephalic presentation, unripe cervix
      (Bishop score less than 5) and reactive NST. The gel was introduced into the
      cervical canal and left in situ for 12 hours. If maturation of the cervix
      occurred, induction was implemented by extraamnial administration of PGE2. In the
      group of patients preinduced with Prepidil there was a significantly greater
      increase of Bishop score and the first stage of labour was shorter during
      subsequent induction of delivery. As to other investigated parameters, the two
      methods did not differ significantly.

PMID- 8998586
TI  - [Prolonged culture of human embryos: comparison of coculture on human tubal
      epithelium and culture in synthetic media].
AB  - The aim of this work was to evaluate prolongation of cultivation time of human
      embryos. The prolongation above the standard limit was implemented (1) by
      coculture of embryos on a monolayer of human epithelial cells and (2) by using a
      synthetic medium. MATERIAL AND METHODS: Ovarian stimulation, oocyte recovery,
      insemination and cultivation up to the pronuclear stage were done in our centre
      in the usual way. Group I: 104 women, prolonged culture by the coculture method.
      The zygotes were placed on the monolayer and cultivated for an other 24 or 48
      hours. Group II: 249 women, prolonged culture in a synthetic medium. The zygotes
      were cultivated up to the 2- to 4-cell stage in standard IVF medium, and then put
      into M3 medium for the next 24 or 48 hours. A transfer of a maximum of 4 embryos
      was done. RESULTS: In group I in 104 women from 341 zygotes 181 embryos (53.1%)
      reached the eight- and more than eight-cell stage, and 76 transfers were done. 15
      pregnancies were achieved (19.4% pregnancy rate). In group II in 249 patients
      from 672 embryos 49.7% of them reached 8- and more than 8-cell stage. 51
      pregnancies were achieved (22.6 pregnancy rate). In the control group of 250 IVF
      after 48 hours cultivation 165 transfers (66.0%) were done, and 16.4% pregnancies
      were achieved, i.e. 6.2% less compared to synthetic medium and 3.3% less than in
      cocultivation. CONCLUSION: There is evidence of better IVF/ET results in case of
      prolonged culture time. The experience in our centre has shown the need of
      reevaluation of the coculture method. The exacting character of its preparation
      and manipulation will have to be replaced by synthetic media in spite of their
      high price.

PMID- 8998585
TI  - [Results of IVF and ET 1992-95 at the Gynecological-Obstetrical Clinic in Olomouc
      -comparison of stimulation protocols].
AB  - The authors compared three types of stimulation protocols used in their
      department in 1992-1995. In the standard protocol they evaluated the use of hMG
      and FSH with regard to the number of abolished cycles and the number of achieved
      pregnancies. They compared protocol No. 1 "standard: CC + G (FSH), protocol No. 2
      "short": GnRH-a + hMG (FSH) and protocol No. 3 "long" GnRH-a + hMG (FSH). They
      evaluated the number of abolished cycles, the effectiveness of the protocols as
      regards the number of obtained oocytes, the number of performed embryo transfers,
      the number of clinical pregnancies/embryo transfers and the number of
      cryopreservations. The abortion rate in relation to the used protocol was also
      evaluated.

PMID- 8998587
TI  - [An active approach to prolonged pregnancy].

PMID- 8998588
TI  - [Contraception in the late reproductive years].

PMID- 8998589
TI  - [Perception of lepers by non-lepers in an urban center in Cameroon].
AB  - We investigated the knowledge and perceptions the general population have about
      leprosy in a sociological study between 1994 and 1995 in the city of Yaounde
      (Cameroon). The sample consisted of 251 respondents aged between 15 and 73 (mean
      30 +/- 18) years old. Asked about the causes of leprosy, 27.8% knew that the
      disease was caused by microbes, 33.4% did not know the cause, 17.4% thought the
      disease to be hereditary and 7.6% due to ill luck. Attitudes to lepers depended
      on the type of behavior considered. Thus, interactions that did not involve
      physical contact were generally welcomed (94%), whereas physical contact was
      shunned: only 45% would tolerate it. Intimacy was rejected by almost all
      subjects. Analysis of the opinion of leprosy victim-oriented social projects
      indicated that most subjects showed humanitarian concern for lepers, but
      preferred public to individual support. The study group did not want to be
      individually or personally committed to any form of special support for leprosy
      victims, but clearly saw the need and justification for public concern for these
      patients.

PMID- 8998591
TI  - [Training of health personnel in the framework of humanitarian action. Choosing
      an assessment model].
AB  - There are very few examples of health training assessment in developing
      countries. Such an undertaking faces a number of difficulties concerning the
      problems inherent to assessment, the particular and unstable nature of the
      environment, and the problems associated with humanitarian action and development
      aid. It is difficult to choose between a formal and a natural approach. Indeed, a
      dual approach, combining quantitative and qualitative data seems best suited to a
      variety of cultural contexts of variable stability. Faced with these
      difficulties, a criteria-based, formative, quality-oriented assessment aimed at
      improving teaching and learning methods should be able to satisfy the needs of
      training professionals. We propose a training assessment guide based on an
      assessment model which aims to improve training techniques using comprehensive,
      descriptive and prescriptive approaches.

PMID- 8998592
TI  - [Variability of home dietary habits of families living in Bamako (Mali) according
      to their socioeconomic status].
AB  - We investigated the influence of standard of living on the dietary and eating
      habits of families in Bamako (Mali). Family meals eaten at home at any time of
      day were studied. Families were selected for the study according to two criteria:
      the place of residence and the domestic commodities and urban investments. Thus,
      24 families were included from affluent and 24 from moderately affluent
      neighborhoods, and 26 families from poor neighborhoods. All families ate three
      meals a day, each including staples and sauce. However, the dishes selected for
      the different meals and their ingredients varied considerably with the family's
      status. Cereals were the main component of breakfast, but the type varied from
      one category of family to another. All poor families and 79% of the intermediate
      group and only 54% of the affluent group ate millet/sorghum. Seventy-five % of
      the affluent, 13% of the intermediate and none of the poor families drank coffee
      at breakfast. Fifty % of the affluent, 29% of the intermediate and 19% of the
      poor families ate rice with nadji sauce at lunch. The quality of the nadji sauce
      varied with economic status. Tigadeguena sauce was eaten with rice in 17% of the
      affluent families, 50% of the intermediate group and 12% of the poor families.
      Very little millet/sorghum was eaten by the affluent at lunch, whereas it was
      included in lunch by over half the poor and one fifth of the intermediate
      families. The diversity of dishes was larger at supper, but only in the affluent
      families which had 2 to 4 different dishes or produce. They included garden
      vegetable salads and stews, with or without bread. Dinner for the intermediate
      and poor families was similar to lunch, that is a cereal base and a sauce. Home
      eating habits also differed according to status. In the affluent families
      breakfast was eaten alone, whereas in the poor families it was a communal meal.
      The intermediate group displayed both patterns. Affluent families tried to
      alternate and diversify their food intake from one meal to another, whereas the
      diet of the poor was monotonous. Most intermediate families tried to alternate a
      small range of staples (rice and traditional cereals) although this necessitated
      reducing the quality of the sauce. Our study shows that eating habits are
      affected by both cultural factors and standard of living.

PMID- 8998593
TI  - [Research and pharmaceutical development on the subject of communicable diseases
      in the intertropical region].
AB  - The development of the antimalarial drugs mefloquine and halofantrine in 1988 by
      American military research teams marked a start in the decline in investment in
      tropical disease research and drug development. The globalization of the market,
      increased clinical costs, and constraints on public health spending caused the
      pharmaceutical industry to concentrate on more profitable market segments
      (cardiovascular drugs, antineoplastics, anti-infection drugs, etc.). The market
      in developing countries represents a large volume, but a very low return because
      the added value is small, generic drugs are used and the state of the populations
      is impoverished. The ten or so drugs that have been developed recently result
      from chance (eflornithine), veterinary research (ivermectin), fortuitous analysis
      of traditional pharmacopoeia (artemether) or reevaluations of former drugs
      (amopyroquine). The deficiency of research and drug development for diseases of
      the intertropical zone has a direct negative effect on public health and also
      reveals health policy inconsistencies, particularly the incompatibility of the
      pharmaceutical industry's interests and international health priorities. The
      problem is also aggravated by the closed approach of external health assistance
      (official development aid) which aims to minimize costs by favoring primary
      health care.

PMID- 8998590
TI  - [The epidemiology of trench fever: a pilot study in homeless people in
      Marseilles].
AB  - Trench fever, cause by Bartonella quintana, disappeared decades ago. Between 1992
      and 1994 about 20 cases were reported in industrialized countries [6, 7]. Some of
      these cases were associated with HIV infection [5], but most affected the
      homeless. The epidemiology of B. quintana is unknown in Europe, but infection and
      transmission are favoured by poor housing and hygiene. This paper describes the
      results of a seroprevalence survey among the homeless living in Marseille. The
      eight major non-profit organizations caring for the homeless in the city
      participated for the four winter months. Four of these organizations also provide
      health care. Each subject who came to be housed for more than one day were asked
      to complete a questionnaire and give a small blood sample by micropuncture. They
      were clearly informed about the aims of the research and were allowed to refuse
      participation freely. All blood samples were tested by the WHO collaborative
      center for ricketssiae using a previously tested and validated immunofluorescence
      technique. The subjects were scored positive if the IgG titer was above 1/100.
      Two hundred and twenty one subjects agreed to participate in the study. Most were
      of French origin (51.4%) and 40% under 40 years old. The seroprevalence was 1.8%
      (IC 95%: 0.05-3.55). None of the four positive subjects presented symptoms and
      clinical examination was normal. All four were over 40 years old; two were of
      French origin, 1 from Algeria and 1 from the Comoro Islands. One had an IgG titer
      above 1/3, 200, possibly reflecting recent contamination and/or severe infection.
      Statistical analysis revealed no significant association between seropositivity
      and housing or hygiene conditions. No socio-demographic data are available about
      the homeless in Marseille and indeed, there is no list of such individuals. It is
      therefore not possible to estimate the representativity of our sample.
      Nevertheless, we show that the homeless include infected individuals. Physicians
      who care for such subjects should prescribe B. quintana serological
      investigations, and organizations that take in these people should implement
      preventive action and health education programs. Any such policy must be designed
      so as to be acceptable to homeless people. This work should also encourage public
      health professionals to investigate more extensively infectious diseases among
      the homeless.

PMID- 8998594
TI  - [Geo-pathologic considerations on the most frequent tumors in Quebec presented in
      1984-1986 and 1989-1991].
AB  - This study describes the geographical variations in the incidence of, and
      mortality due to, the most frequent cancers in Quebec. They are breast, colon and
      tracheal, bronchial, and lung cancers in women and prostate, colon and trachea,
      bronchial and lung cancers in men. Data for the periods 1984 to 1986 and 1989 to
      1991 for the whole of the Quebec Community Health Department are reviewed. A
      direct method of standardization, with the world population as the reference
      population, was used to allow comparison of geographical units. The ranking
      correlation method was used to test correlations for the various cancer sites.
      There were significant coefficients between the two periods only for lung cancer
      for both sexes, for both incidence and mortality. The spatial autocorrelation
      method was used to determine the presence or absence of a geographical
      configuration from the estimated rates. Moran I values were positive and
      significant for the two periods for lung cancer associated mortality and for the
      incidence of breast cancer. This implicates local factors (probably associated
      with lifestyle). The results for the incidence of lung cancer among men and women
      were similar for the period 1989 to 1991. The advantages and limitations of the
      methods used and also the data available are considered.

PMID- 8998596
TI  - [An exhaustive study of the frequency of vision disorders in children 5-18 years
      of age at a Lebanese school].
AB  - From October 1995 to June 1996, 935 children (439 boys and 496 girls) aged
      between 5 and 18 years old (mean 11.6 years) were examined in their school in
      Saida (Lebanon) for visual disorders. All examinations were conducted by the same
      investigator (MK) and consisted of an evaluation of both external oculomotricity
      and visual acuity (VA) for far vision only. Sixty-five children were examined
      twice to check the validity of the results. The children were classified into two
      groups according to the findings: -Normal: children with VA above 14/20 degrees
      (the two eyes being equal or differing by less than 4/20 degrees) and normal
      oculomotricity. -Abnormal: children with VA below 14/20 degrees and/or
      oculomotricity disorder. Seventy percent of the ametropic group were unaware of
      their visual defect which can lead to the development of amblyopia. This is of
      importance, because the longer treatment for amblyopia is delayed, the lower the
      chance of complete recovery. We hope that this study will stimulate other
      studies, including those addressing all children over two years old, and that
      this in turn will lead to measures to improve the ocular health of the
      population.

PMID- 8998595
TI  - [Atypical mycobacterial skin infections].
AB  - The incidence of cutaneous atypical mycobacterial infections is increasing. Their
      clinical presentation is variable. The atypical mycobacteria are difficult to
      culture and thus diagnosis can be difficult to establish. PCR (Polymerase Chain
      Reaction) and mycolic acid analysis have recently been used for mycobacterial
      species identification, but are not routinely used. Risk factors for cutaneous
      atypical mycobacterial infection include (1) immunodepression due to HIV
      infection, lymphoma, leukemia or immunosuppressive therapy. Immunodepression is
      responsible for the emergence of cutaneous infections by a large variety of
      atypical mycobacterial species, particularly in industrialized countries. (2) The
      natural environment is directly responsible for the emergence of cutaneous
      infections but a small number of atypical mycobacterial species including M.
      marinum in Europe and North America, and M. ulcerans in the tropics. (3) The
      medical environment when sterilization is inadequate is also not uncommonly
      responsible. Clinical features are rarely specific for mycobacterial species, and
      thus analysis of factors relevant to treatment is more important than species
      classification. We describe environmental forms (Buruli ulcer caused by M.
      ulcerans is endemic in the tropics, and swimming pool granuloma which is the
      aquatic form of M. marinum infection), opportunist forms caused by various
      species in immunodepressed hosts and iatrogenic and accidental forms mostly due
      to M. fortiutum and M. chelonei. We review the literature and update the clinical
      characteristics and risk factors for these diseases.

PMID- 8998597
TI  - [Lecture notes. Attention AIDS!].

PMID- 8998598
TI  - Chemical synthesis and actions of 11,12-thiirano-hepoxilin A3.
AB  - A novel analog of hepoxilin A3 has been chemically synthesized in which the 11,12
      epoxide group has been altered to a thiirano group. This has been accomplished
      through allylic rearrangement of unnatural (11 R, 12 R)-hepoxilin B3 under
      Mitsunobu conditions, first into unnatural (11 R, 12 R)-hepoxilin A3, followed by
      conversion of this compound with inversion of the epoxide centers into the
      thiirano-hepoxilin A3 having the natural 11 S, 12 S configuration. We also report
      herein evidence showing that thiirano-hepoxilin A3 raises intracellular calcium
      concentrations in intact human neutrophils.

PMID- 8998599
TI  - High-density lipoprotein inhibits the synthesis of platelet-activating factor in
      human vascular endothelial cells.
AB  - The regulation of platelet-activating factor (PAF) synthesis by serum
      lipoproteins was investigated in human umbilical vein endothelial cells. High
      density lipoprotein (HDL) inhibited PAF synthesis in agonist (thrombin,
      histamine, and A23187)-stimulated endothelial cells, that was determined by
      incorporation of [3H]acetate into PAF and by bioassay. The inhibition by HDL was
      increased in a concentration-dependent manner, but was reversed as the
      concentration of thrombin increased. HDL did not affect the time course of PAF
      production. HDL lipids suppressed the PAF production to a lesser extent than HDL.
      The reduction of PAF accumulation in HDL, did not result from degradation of PAF
      but inhibition of PAF synthesis, which was mainly mediated via the blockade of
      acetyl-CoA:1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase
      activation. HDL did not prevent the release of [3H]arachidonic acid in thrombin
      stimulated endothelial cells. The binding of 125I-HDL to endothelial cells and
      its uptake were not enhanced by thrombin stimulation. These results demonstrate
      that HDL may inhibit the activation of acetyltransferase by thrombin at the cell
      surface. This observation may explain a part of mechanism of HDL action.

PMID- 8998600
TI  - [Comparison of various methods of hemoculture tests].
AB  - Three methods of blood cultivation were compared: collection of blood into
      transport bottles containing only dextran-sulphate, collection into cultivation
      media containing bottles (aerobic, anaerobic and paediatric Dulab) and the semi
      automatic continuous blood culture system (Bactec 9000, using aerobic, anaerobic
      and paediatric bottles). A total amount of 1.250 blood samples collected from 626
      patients was divided equally into the compared bottles and processed parallelly.
      The yield of the Bactec aerobic bottles was significantly higher than the yield
      of the transport bottles and aerobic Dulab bottles (p < 0.001). However, this
      result was influenced by the higher rate of contaminating bacteria isolated from
      the aerobic Bactec bottles. The yield of the aerobic Dulab bottles was higher
      than the yield of the transport bottles (p < 0.01). The average time needed for
      the detection of microorganisms in the Bactec bottles was by 24 hours shorter
      than in the transport bottles and by 19 hours shorter than in the aerobic Dulab
      bottles (p < 0.001). The difference between the yields of the anaerobic and the
      paediatric bottles in our study was not significant. The time needed for the
      detection of microorganisms was by 17 hours shorter in the anaerobic Bactec
      bottles than in the transport bottles (p < 0.05).

PMID- 8998601
TI  - [Diagnosis of infections caused by atypical mycobacteria].
AB  - Laboratory methods used for the differentiation of acid resistant rods of the
      genera Mycobacterium make use of their biological properties, in particular the
      growth rate on cultivation media, pigment formation, sensitivity for biochemical
      substances incl. antibiotics, biochemical activity and different relations to
      animal hosts. By testing these properties it was possible to classify
      mycobacteria into groups or identify different species in more detail.

PMID- 8998602
TI  - [Epidemiology of meningococcal infections in military communities within the
      catchment area of the Military Medicine Institute in Plzen 1994-1995].
AB  - The authors submit information on the epidemiological position as regards the
      prevalence of invasive meningococcal diseases in military communities on roughly
      half the territory of the Czech Republic in 1994-1995. For illustration of the
      clinical picture the authors present brief case-histories focused on the
      development of the different diseases before admission to hospital. The authors
      submit results of examination of carriership of Neisseria meningitidis in
      military communities focused on the serological group C. Analysis of the
      epidemiological position and surveillance of meningococcal infections conducted
      by the National Reference Laboratory for meningococcal infections in the National
      Institute of Public Health and facilities of the military hygiene and
      epidemiological service in 1993-1995 were the basis for joint sessions which
      culminated by the decision to start vaccination of Czech Army conscripts,
      starting in July 1995. This procedure was approved by the Chief Hygiene Officer
      of the Czech Republic and it was recommended to continue monitoring of
      carriership in vaccinated groups of conscripts.

PMID- 8998603
TI  - [Initial results of monitoring hepatitis E virus antibodies in selected
      population groups in the West Bohemia Region. Preliminary report].
AB  - The authors examined sera of 269 subjects for the presence of antibodies against
      the hepatitis E virus. In the group of patients with acute hepatitis (after
      elimination of hepatitis A, B and C) antibodies were detected in 27.8%, in the
      group of gypsies with non-hepatic disease in 4.8%, in a group of venereological
      patients in 2.4%. The conclusions from the preliminary results confirm the
      circulation of the hepatitis E virus in our population and its importance in the
      etiology of liver disease, in particular in more advanced age groups.

PMID- 8998604
TI  - [The effect of pharmacodynamic parameters of pefloxacin on elastase and protease
      activity in Pseudomonas aeruginosa].
AB  - The effect on Pseudomonas aeruginosa virulence factors (elastase and proteinase)
      after short-time treatment (30 min) with suprainhibitory (2x or 4x MIC) as well
      as with supra-subinhibitory concentrations (2x MIC + sub-MICs or 4x MIC + sub
      MICs) of pefloxacin was studied. An effective decrease of elastase activity (to
      42.6% of the control value) was observed only after higher suprainhibitory
      antibiotic concentration. More significant depression of the activities tested
      was found after the postantibiotic effect of subinhibitory concentrations.
      Elastase as well as proteinase activity were suppressed by supra-subinhibitory
      concentration of 4x MIC + 0.1x MIC to 13.1% or 37.9%, as compared to controls.

PMID- 8998605
TI  - [Detection of chlamydia in the intestines and lungs in pigeons and humans].
AB  - Attempts were made to detect Chlamydia sp. by direct immunofluorescence (IF) in
      intestinal and lung tissues collected from wild town pigeons, young reared
      pigeons, and human corpses. Chlamydia in any organ were detected in 86.6% of the
      427 adult pigeons and 27.3% of 16 young pigeons. Positive IF results were in
      intestinal and lung samples, collected from 427 adult pigeons, in 34.3% and
      40.05% of the birds, respectively. Human (n = 100) intestinal and lung tissues
      were positive in 22% and 20% of the corpses, respectively. Titres 1:20 and higher
      were demonstrated by CF in 53.86% of the 427 adult pigeons. The highest titre
      found was 1:5 120.

PMID- 8998607
TI  - [Long-term follow-up of nosocomial rotavirus infections at the Infectious
      Diseases Clinic of the Medical School Hospital in Plzen (1987-1994)].
AB  - The authors evaluated in 1987-1994 the incidence of nosocomial rotavirus
      infections during hospitalization in 1718 junior children, 450 senior children
      and adults admitted with diarrhoeal diseases. Rotavirus infection was revealed in
      6.2 and 1.3% of the patients resp. During hospitalization the rotaviruses were
      the most frequent causal agent of nosocomial infections. Hospital infection was
      contracted regardless of the initial diagnosis most frequently by patients aged 0
      12 months. The majority of nosocomial rotavirus infections was associated with
      symptoms of diarrhoeal disease, on average symptomatic infections prolonged the
      hospitalization period by 4.2 days. The authors discuss the possibility to
      influence the incidence of these infections.

PMID- 8998606
TI  - [An imported case of hemorrhagic fever with renal syndrome].
AB  - The authors present a case of haemorrhagic fever with renal syndrome imported
      from a region of endemic occurrence of hantaviruses in the Balkans. The patient
      contracted the infection in connection with service in the Czech UNPROFOR unit.
      The affection manifested itself as renal insufficiency and required a total of
      seven haemodialyses for complete recovery. The epidemiological context and
      clinical course of the disease are described in detail.

PMID- 8998608
TI  - [Pharmacoepidemiology. I].
AB  - The present paper deals with the problems of pharmacoepidemiology, particularly
      from the aspect of defining the concept and elucidating the content of the
      discipline. The author's attention was further paid to one of the components of
      pharmacoepidemiology-the drug utilization, including the studies of the DUR and
      DUE types.

PMID- 8998609
TI  - [Thin-layer chromatography analysis of methamphetamine in urine samples].
AB  - The paper investigated the chromatographic conditions for TLC analysis of
      metamphetamine on silica gel and the lipophilic stationary phase RP V 18 in order
      to qualitatively analyze the drug in urine samples. Attention was also paid to
      chemical detection. Five detection reagents were tested, out of which Fast Black
      K salt, yielding orange-red spots with a detection limit of 1 microgram, proved
      to be the best. In the analysis of metamphetamine in the samples of model urine,
      the best results were achieved on Kieselgel. Using the developing system ethyl
      acetate-ethanol-concentrated solution of ammonia (36:2:2), a complete separation
      of the metamphetamine spot from the spots of ballast from the biological matrix
      was achieved.

PMID- 8998611
TI  - [Natural substances with antioxidant activity].
AB  - The review summarizes information about natural substances of phenolic nature
      (flavonoids, hydroxycinnamic acids, tannins), in which antioxidant effects and
      ability to quench free radicals have been demonstrated. A number of substances
      seem to be perspective in the treatment of cardiovascular diseases, cancer and
      liver diseases.

PMID- 8998612
TI  - The new demand area: nurse practitioners receive numerous job offers.
AB  - Demand for nurse practitioners continues to increase. Hospitals, long-term care
      facilities, out-patient areas, and ambulatory settings cannot find enough
      qualified applicants for their positions. Schools cannot take all the qualified
      applicants into their programs because of shortages of faculty or student
      practice sites. Meanwhile, many nurse practitioners report six or more job offers
      upon graduation. This author describes this new trend and strategies you can take
      now to prevent recruitment problems in the future.

PMID- 8998610
TI  - [The effect of piperazine analogs of aryloxyaminopropanol (IIIq and IIIb) on the
      occurrence of reperfusion dysrhythmias in an in vivo experiment on rats].
AB  - The present experimental study reports the beneficial effects of newly
      synthetized substances IIIq and IIIb in vivo. These aryloxyaminopropanol drugs
      have been shown to antagonize the contraction caused by calcium comparable to
      verapamil and flunarizine in the model of the isolated guinea pig terminal ileum.
      Effects of substances on both the incidence of arrhythmias during ischemia and
      the reperfusion period and mortality were investigated in the rat model ischemia
      reperfusion injury. We can conclude that compound IIIq in a dose of 10(-6) mol/kg
      is effective in reducing the incidence of reperfusion-induced arrhythmias.
      Substance IIIb (10(-6) mol/kg) administered before ischemia was not able to
      suppress arrhythmias in the rat model of myocardial infarction and reperfusion.

PMID- 8998613
TI  - Creating a sense of direction: decreasing resistance to restructuring changes.
AB  - In-patient hospital days will continue to decline as health care and services
      shift more and more to a community and wellness focus. The declining census
      forces the need to restructure acute care patient units. This author describes
      how to decrease physician and nursing staff resistance to restructuring by
      creating a sense of direction.

PMID- 8998614
TI  - Proactive downsizing: merging two units into one.
AB  - Downsizing is a word firmly entrenched in the vocabulary of healthcare
      institutions. So, nurse managers, will your area be downsized by choice or by
      mandate? Will you be proactive or reactive? The decision is up to you. Two
      surgical nurse managers recognized the signs of the times and developed their own
      downsizing proposal to merge two units. Here are the steps they followed for a
      proactive approach to combine two clinical units into one.

PMID- 8998615
TI  - Helping new graduates find jobs: a responsibility of nursing leaders.
AB  - Part of being a profession is providing for entry of new members. During this
      period of restructuring, it is the responsibility of current nursing leaders to
      help new graduates deal with the job entry problem. This author, who has
      experience working with students who are concerned about not finding a job in
      nursing, describes strategies that nursing leaders can use to help new graduates
      enter into the profession.

PMID- 8998616
TI  - Strategies for improving job security: decreasing anxiety from restructuring.
AB  - Nurses are worried about the future of nursing and, more specifically, about the
      future of their own job. This author who is experienced in working with nurses on
      job security issues and clarifying layoff policies suggests strategies that can
      help improve nurses' feelings of job security even during this time of
      restructuring.

PMID- 8998617
TI  - The VP of nursing challenge: integrating all patient services.
AB  - Restructuring nursing service goes beyond restructuring nursing roles at the unit
      level. Even the Vice-President (VP) of Nursing role needs to be evaluated and
      revised, so it is a viable role for leading health care services into the 21st
      century. This experienced author describes how to expand the VP of Nursing
      position to VP of Patient Services so she or he can lead patient-care
      professionals in focusing on the patient without territorial boundaries.

PMID- 8998618
TI  - Journal evolution continues.

PMID- 8998619
TI  - Prophylactic vitamin K--should midwives be involved in its administration?

PMID- 8998620
TI  - Marfan's syndrome.

PMID- 8998621
TI  - Obstetric cholestasis. Itching in pregnancy? Midwives must be alert.

PMID- 8998622
TI  - Obstetric cholestasis. Diagnosis and treatment for cholestasis in pregnancy.

PMID- 8998624
TI  - Managing the market.

PMID- 8998625
TI  - Marketing maternity care. A step-by-step guide.

PMID- 8998623
TI  - Royal society of medicine forum on maternity & the newborn. Debate: this house
      believes that Caesarean section rates in the United Kingdom are too high.

PMID- 8998626
TI  - Where the reforms do & don't deliver.

PMID- 8998627
TI  - Midwives' insurance.

PMID- 8998628
TI  - Response of the RCM to criticisms regarding independent midwives' insurance.

PMID- 8998629
TI  - Pregnancy loss and the death of a baby. Guidelines for professionals.

PMID- 8998630
TI  - Pregnancy loss and the death of a baby. A training pack for professionals.

PMID- 8998631
TI  - Midwives and money matters: taxation and rebates.

PMID- 8998632
TI  - Pregnant prisoners--RCM recommendations accepted.

PMID- 8998633
TI  - [Pelvic fracture with shock-inducing retroperitoneal bleeding and concomitant
      lower extremity ischemia syndrome: discussion of management exemplified by a case
      report].
AB  - BACKGROUND: Initial treatment of severe pelvic fracture consists of appropriate
      resuscitation and early pelvic reposition and stabilization. Concomitant
      retroperitoneal arterial bleeding in a hemodynamically unstable patient in
      combination with lower extremity ischemia make early management decisions very
      difficult and the mortality rate of this entity of injuries is extremely high.
      CASE REPORT: We report on a successful treatment of a 36 year old skier, referred
      in hemorrhagic shock, who had sustained a severely displaced both column fracture
      of the right acetabulum, an unstable pelvic ring injury on the left and a
      retroperitoneal bladder rupture. He developed complete ischemia of the right
      lower extremity. Angiography revealed an obliteration without extravasation of
      the external iliac artery and allowed treatment of a right superior gluteal
      artery disruption by embolization. The right lower extremity ischemia was
      revascularized with a subcutaneous femoro-femoral bypass graft. Delayed internal
      fixation of the right acetabulum and exploration of the iliac vasculature was
      done through an ilio-inguinal approach. Simultaneously, the cross-over bypass
      could be removed. After 18 months, the patient recovered without any ischemic
      symptoms, but continues with a mixed sciatic nerve lesion. DISCUSSION AND
      CONCLUSIONS: The combination of severe retroperitoneal arterial bleeding and
      total ischemia of the lower extremity requires immediate surgical therapy. Direct
      exploration of the retroperitoneum, however, can be fatal and should be avoided
      if the iliac vessels are angiographically intact or if a hemorrhage is
      controllable by an embolization procedure. Extraanatomic temporary
      revascularization of the lower extremity should be envisaged when a lower leg
      ischemia due to obliteration or compression of major intrapelvic vessels cannot
      be directly and immediately treated.

PMID- 8998635
TI  - [Feedback-controlled weight bearing following osteosynthesis of the lower
      extremity].
AB  - Truly partial weight bearing by usual mode of mobilisation after an operation of
      the lower limb is not a realistic goal. Frequent and massive overloading could
      recently be shown in a series of patients with joint replacements. Significant
      improvements in the loading pattern could be demonstrated with the use of an
      acoustic feedback system. Our goal was to test the clinical application of this
      method by using a similar system in the form of an insole-installed device. In
      the same trial, data on the real weight bearing pattern with prescribed loading
      after osteosyntheses was to be collected with and without the feedback device. We
      measured weight bearing continuously in two groups of patients. The first group
      was mobilised in the usual manner whereas the second group was acoustically
      alerted to overloading when passing the limit of 15 kg by a sensor device in the
      insole. Our results showed that 40.8% of steps made by patients mobilised in the
      usual manner were massively overloaded whereas 12.7% of steps in the second
      feedback-group produced even minor overloading. Apart from certain technical
      difficulties, the method was well accepted by the patients. The usual method of
      progressive weight bearing is unreliable. The value of partial weight bearing
      after internal fixation of the lower limb remains to be evaluated. In cases in
      which partial weight bearing is recommended, more attention should be paid to
      observing the prescribed limits and a reliable system that alerts the patient of
      excessive weight bearing would be most useful. For routine use in clinics a
      technically more reliable PMT Feedback System has to be developed.

PMID- 8998634
TI  - [Autologous blood transfusion: results with routine use of autologous blood
      transfusion, normovolemic hemodilution and postoperative retransfusion of
      drainage blood salvaged with the Solcotrans system].
AB  - BACKGROUND: Although the medical advantages of autologous blood transfusion are
      undisputed today, it has been established only in a few hospitals. At our
      hospital we have employed infusion of previously stored autologous blood and
      normovolemic hemodilution routinely in all patients undergoing major orthopedic
      surgery since June 1, 1986. QUESTION: In this study the efficacy of additionally
      infusing salvaged drainage blood postoperatively in reducing the need for
      homologous blood transfusion was examined. METHOD: From June 1, 1990 through
      December 30, 1993 the effectiveness of autotransfusion techniques with the
      additional use of postoperative infusion of salvaged blood was studied in 318
      patients. RESULTS: Preexisting anemia with hemoglobin value of less than 11 g/dl
      proved to be the only contra-indication for autologous blood transfusions and was
      found in 8 (2.5%) of our patients. These patients were not eligible for the
      autologous blood program. The 310 remaining patients were all given their
      previously stored autologous blood with hemodilution. In addition, 261 of these
      patients (84%) were also given salvaged drainage blood postoperatively using the
      solcotrans system or solcotrans-plus-orthopedic system. Of the total 310
      patients, 218 (70.3%) did well without homologous blood. This was also true for
      206 (78.9%) of the patients treated with all 3 autotransfusion procedures. No
      complications implicating the autotransfusion techniques were encountered. In
      addition, the method described and as employed in our hospital led to a cost
      reduction of about 40% compared to homologous transfusions. DISCUSSION AND
      CONCLUSION: The efficiency of autologous blood transfusions and hemodilution in
      reducing the need for homologous blood at our hospital, as previously described,
      could be increased by 22% using the solcotrans system. The advanced age of our
      patients (average 73 years) and the number of preexisting, in part considerable,
      medical problems permit the conclusion that these autotransfusion techniques are
      quite well tolerated. The contraindications could be reduced to a few exceptions.
      The logistics necessary to carry out these procedures are simple and can be
      achieved with a bit of will and effort in all hospitals including those of middle
      and small size.

PMID- 8998636
TI  - [Percutaneous iliosacral screw fixation of vertical unstable pelvic ring
      fractures].
AB  - In type C pelvic ring fractures ORIF is the treatment of choice. Early definitive
      fixation often is not possible due to severe soft tissue injuries and hemorrhage.
      The percutaneous iliosacral screw fixation with the patient supine offers a
      minimally invasive and definitive fixation method of the posterior unstable
      pelvic ring also in acute situations. Our first experience shows that a ventral
      stabilisation is necessary in combination with one dorsal screw. Both fixations
      are managed in the supine position of the patient during one anesthesia.

PMID- 8998637
TI  - [Osteocartilaginous reconstruction, research and clinical application].
AB  - Facing the problem set by losses of osteo-cartilagenous substances around the
      little bones, the finger- and toe-joints for example, the authors scanned a way
      different from that of amputation or arthrodesis: the functional rebuilding with
      the help of substitution grafts. An exploratory research conducted on 21 rabbits
      in Bordeaux in 1990 allowed to test the coupling of two bio-materials used in
      surgery here and now, a coupling which has not shown any side-effect and whose
      benefit is to obtain a non-deformable mass, colonizable by osteoblastic cells.
      The loss of articular substance suffered by a patient in his fingers in 1992
      profited by this bone-rebuilding technique. The use of an external articulated
      stabilizer was an important provisional support during the colonization of the
      grafts by the osteoblasts. The difference of time in the osseus rebuilding
      between the rabbits on the one hand, and the human being on the other, is
      recorded.

PMID- 8998639
TI  - [Long-term results following fibulo-tarsal ligament reconstruction. Comparison of
      the Watson-Jones and the (modified) Chrisman-Snook techniques].
AB  - The chronic lateral instability of the ankle joint presents a major problem after
      an acute tear of the lateral ankle ligaments. In this study we controlled 26
      patients clinically and radiologically, who had undergone ankle ligamentoplasty
      (Watson-Jones and Chrisman-Snook (modified) techniques) between 1987 and 1991
      because of chronic lateral ankle instability. The aim of this study was to
      evaluate if the more difficult Chrisman-Snook technique had better results. The
      patients had been suffering from a chronic lateral instability on the average of
      6-7 years before surgery. The operations were performed by experienced surgeons.
      The follow-up-period was 5 years. The reduced postoperative ankle mobility
      revealed no clinically relevant difference between the two groups. Also, the
      complication rate were the same. The functional assessment showed good or
      excellent results in over 80% for both groups. Long-term clinical results of the
      two operations are similar and gave good or excellent results in more than 80% of
      the cases and are similar to other reconstructive techniques.

PMID- 8998638
TI  - [Carpal ligament lesions associated with fresh distal radius fractures:
      arthroscopic study of 54 cases].
AB  - AIM: Intracarpal ligamentous tears and fractures of the distal radius may have a
      similar injury mechanism. We performed arthroscopy of the wrist in 54 patients
      with distal radius fracture to find out the frequency of associated ligamentous
      tears. RESULTS: 41% of the patients with an extraarticular fracture of the distal
      radius had at least one severe ligamentous tear of a carpal ligament. In the
      group of patients with intraarticular fracture we detected ligamentous tears even
      in 89%. Most frequent were tears of the lunotriquetral ligament. DISCUSSION:
      Associated ligamentous tears are more common than expected. These tears may be of
      importance in the outcome of treatment of distal radius fractures.

PMID- 8998640
TI  - [Functional therapy using a laced ankle brace in supination trauma of the ankle
      joint with lesions of the capsule-ligament apparatus].
AB  - Based on the results of comparable studies, patients of the Kantonsspital
      Liestal, who had sustained injuries of the lateral capsulo-ligamentous structures
      of the ankle are treated with early functional therapy. Osseous lesions are
      excluded prior for treatment. Since 1990 a special ankle brace with laces is
      used. A standardised questionnaire was developed for follow-up. Subjects of
      interest were: the patients individual experience regarding treatment method and
      the patients subjective feelings regarding stability, remaining symptoms and
      limitations in daily activity. 89 questionnaires were returned. 91% rated the
      treatment as excellent or good. 15% reported a chronic instability. Only 1
      patient underwent secondary reconstruction of the lateral ankle ligaments.

PMID- 8998641
TI  - [Management of unstable shaft fractures of the lower extremity in children using
      the external fixator].
AB  - METHOD: Since 1993 we have treated 30 children between 2 and 15 years with 31
      unstable tibial and femoral shaft fractures. We perform closed reduction und X
      ray control and stabilize the fracture using the monotube-fixator, system
      Howmedica. The advantages of this system are based on the self-drilling, self
      cutting screws and the simple dynamization. DISCUSSION: The treatment of
      dislocated, instable fractures of the tibial and femoral shaft in children using
      traction method is related with a long hospital stay in an uncomfortable
      position. The traction method leads to bone healing, but with a high rate of
      deformity after reposition. We treat the shaft fractures of the lower extremity
      using the external fixation. This method allows to reach early weight bearing
      mobilisation, it is related to a shorter hospital stay. The child is already one
      day after initial treatment allowed to walk with full weight bearing. The
      treatment with the external fixation is a modification of the traction method.
      CONCLUSION: We think to have a good concept of treatment using external fixation
      in children with unstable fractures of the femur and tibia shaft. The
      disadvantages namely pin tract infections, general anesthesia for removal and
      difficulties with the reduction are overruled by the advantages as short hospital
      stay, early weight bearing mobilisation and early return of the child to his own
      environment.

PMID- 8998642
TI  - Reforms round-up. There is a better way.

PMID- 8998643
TI  - Learning about latex allergy.

PMID- 8998645
TI  - The face of private health care.

PMID- 8998644
TI  - The ethics of bathing.

PMID- 8998646
TI  - Expanding private care.

PMID- 8998647
TI  - Ethical networking.

PMID- 8998648
TI  - What's case management?

PMID- 8998649
TI  - Learning to work as partners.

PMID- 8998650
TI  - Preventing AIDS through song. Interview by Gay Williams.

PMID- 8998651
TI  - Facing up to faulty practice.

PMID- 8998653
TI  - Political support for plunket.

PMID- 8998652
TI  - Seeking ways of working biculturally.

PMID- 8998654
TI  - A poet laureate of nursing. Interview by Laura Ninger.

PMID- 8998655
TI  - Medicine men and monkey bites--a trip to Northern Mozambique.

PMID- 8998666
TI  - [Prevention of recurrence of acute biliary pancreatitis by endoscopic
      sphincterotomy].
AB  - The aim of this study was to know if endoscopic sphincterectomy could be an
      alternative to cholecystectomy in high surgical risk patients that have suffered
      acute biliary pancreatitis. Between January 1992 to December 1995 endoscopic
      sphincterectomy was carried out in 52 high surgical risk patients who had
      suffered an episode of acute biliary pancreatitis. The lithiasic gallbladder was
      not removed. The mean age was 75.6 years (35-91). After a follow up of 15.9
      months (1-46.5), no patient suffered from a new episode of acute pancreatitis.
      Six patients (12%) required cholecystectomy due to complications derived from the
      lithiasic gallbladder. Endoscopic sphincterectomy is an effective alternative to
      cholecystectomy in the prevention of new episodes of acute biliary pancreatitis
      in patients with lithiasic gallbladder and high surgical risk. The complications
      of the lithiasic gallbladder in situ after endoscopic sphincterectomy are
      relatively infrequent.

PMID- 8998667
TI  - [Severe hepatotoxicity of tuberculostatic agents. Increase in the incidence].
AB  - Hepatotoxicity by antituberculous drugs is well known. Nonetheless, severe liver
      involvement is infrequent. Several series of fulminant hepatitis by
      antituberculous drugs have recently been reported with a much greater frequency
      than previously reported. The present study describes the authors' experience
      which, similar to other groups, has shown a marked increase with respect to
      previous experience. During 1994 5 patients with acute severe hepatitis
      associated to antituberculous drugs were admitted to the authors' unit. The mean
      age of the patients was 43 years (range: 25-62). Two patients were healthy HBsAg
      carriers, one undergoing enzymatic inducer treatment and was anti-HIV positive.
      Another patient presented compensated liver cirrhosis by HCV. The 5 cases
      received combined isoniazid and rifampicin and four had also received
      pyrazinamide. Four patients presented hepatic encephalopathy. Of these cases,
      three could not undergo emergency liver transplantation because of
      contraindications and died due to complications of acute severe liver failure.
      Another patient evolved favorably following emergency liver transplantation. The
      only patient who presented good evolution with conservative treatment and who did
      not present hepatic encephalopathy had discontinued isoniazid because of the
      finding of slight hypertransaminasemia during a routine analytical control.
      Several risk factors have been reported for the appearance of hepatotoxicity by
      antituberculous drugs. The factor of greatest clinical importance for the
      development of severe hepatotoxicity is probably continuation of the treatment
      once hepatic dysfunction has initiated. The important increase in cases of severe
      toxicity urges the need for strict analytical monitoring following initiation of
      treatment.

PMID- 8998668
TI  - [Gastric adenocarcinoma in hamartomatous polyp in Peutz-Jeghers syndrome].
AB  - The Peutz-Jeghers syndrome is characterized by gastrointestinal polyposis and
      mucocutaneous melanin pigmentation. Between the complications are the appearance
      of gastrointestinal neoplasms. There is an increasing evidence suggesting the
      hamartoma-adenoma-carcinoma sequence in Peutz-Jeghers syndrome. We present a 32
      years-old man with Peutz-Jeghers syndrome who developed an adenocarcinoma arising
      in a gastric hamartomatous polyp. We discuss the risk to develop gastrointestinal
      neoplasms and the necessity for periodic surveillance.

PMID- 8998669
TI  - [Pseudotumorous hepatic tuberculosis: laparoscopic appearance].
AB  - Local hepatic tuberculosis without active pulmonary or miliary tuberculosis is an
      uncommon diagnosis. Even less common is the finding of a nodular form of local
      hepatic tuberculosis. There is a growing incidence of the disease related to
      human immunodeficiency virus. The authors report a case of pseudotumoral hepatic
      tuberculosis in a patient without AIDS, manifesting as prolonged fever, diagnosed
      previously as metastatic liver. Imaging studies of the liver and laparoscopic
      findings suggested metastatic disease. The correct diagnosis was made by
      histology of biopsies obtained in laparoscopy, which is an easy and cheap method,
      with less morbidity and mortality than surgical intervention. The case report
      illustrates the difficulty in reaching the correct diagnosis, most often confused
      with carcinoma of the liver, primary or metastatic. A greater awareness of this
      rare clinical entity may prevent needless surgical intervention since the
      majority of patients respond well to antituberculous chemotherapy.

PMID- 8998670
TI  - [Cholestatic hepatitis caused by midecamycin].
AB  - Hepatotoxicity by macrolide antibiotics, particularly erythromycin and
      derivatives, is a side effect extensively described in the literature.
      Midecamycin is a semi-synthetic derivative of this family with a wide safety
      margin of which isolated references of possible secondary hepatobiliary effects
      have been referred. The present clinical observation describes a case of
      cholestatic hepatitis which, in our opinion, was related to the administration of
      diacetyl midecamycin which evolved favorably following discontinuation of the
      drug. Despite its exceptional frequency and based on the wide therapeutic
      diffusion of this group of antibiotics, we believe this case to be of interest.

PMID- 8998671
TI  - [Splenic rupture in acute pancreatitis].
AB  - The case of a 42-years-old male with acute pancreatitis of ethanol origin and
      formation of pseudocysts in the tail of the pancreas is presented. The patient
      suddenly presented a picture of hypovolemic shock caused by rupture of the
      spleen. Emergency splenectomy with resection of necrotic tissue was performed and
      thrombosis of the splenic vein was observed. The patient evolved satisfactorily
      following surgery.

PMID- 8998672
TI  - [Palliative treatment of esophageal cancer].

PMID- 8998675
TI  - [Spontaneous bacterial peritonitis caused by Pseudomonas aeruginosa].

PMID- 8998673
TI  - [Aquaretic agents].

PMID- 8998674
TI  - [Pharmacological bases of non-steroidal anti-inflammatory analgesics].

PMID- 8998676
TI  - [Isolated hypertransaminemia as a form of presentation of celiac disease in
      adults].

PMID- 8998677
TI  - Infusional chemotherapy. Symposium proceedings. Paris, France, September 14-15,
      1995.

PMID- 8998678
TI  - Modulation of the pituitary and basomedial hypothalamic lysyl-aminopeptidase
      activities be beta-estradiol and/or an aqueous extract of Physalis alkekengi
      fruits.
AB  - Injections of an aqueous extract of winter cherry fruits (Physalis alkekengi) to
      adult female cycling rats by an intraperitoneal route resulted in the diminution
      of the pituitary lysyl-aminopeptidase (Lys-AP) activity by 50% and that of the
      basomedial hypothalamus (BMH) by 45%. Administration of daily doses of 3.75, 7.5,
      and 15 micrograms beta-estradiol for a period of 5-8 days to such animals
      increased pituitary Lys-AP activity from 31% to 61.5% and that of BMH from 20% to
      87%, respectively. Administration of the same doses of beta-estradiol along with
      a given dose of the aqueous extract for 7-8 days diminished Lys-AP inhibitory
      effect of the extract in both the pituitary and BMH and eventually, at the
      highest dose of beta-estradiol, increased the pituitary enzyme activity by 9% and
      that of BMH by 5%. It is concluded that Lys-AP enzymes of both tissues, being
      estrogen-induced proteins, are inhibited by the estrogen antagonistic principle
      of the winter cherry aqueous extract. It is further suggested that BMH Lys-AP
      activity may be used as an enzyme marker for the action of beta-estradiol in
      hypothalamus.

PMID- 8998679
TI  - Bone marrow stromal cells are load responsive in vitro.
AB  - Mechanical load-related effects on bone marrow stromal cells in vitro have been
      investigated. A dose response of a cyclical load of 1 Hz between 350 ustrain and
      2500 ustrain applied to 10-day-old cultures resulted in elevated alkaline
      phosphatase levels and the number of cells expressing this protein after 2 days.
      No significant changes in the number of cells expressing or the production of
      collagen type 1 was observed. A critical stage of development of the cultures
      must be reached before load-related elevation in alkaline phosphatase expression
      could be measured independent of the stage at which loading was applied. Using a
      prostaglandin inhibitor at concentrations previously used in vivo, the load
      response was abolished. We have demonstrated that bone marrow stromal cells are
      load responsive in culture and have made preliminary studies into determining the
      involvement of prostaglandins in this process.

PMID- 8998680
TI  - ATP and adenosine act as a mitogen for osteoblast-like cells (MC3T3-E1).
AB  - Extracellular ATP, and to a lesser extent adenosine, an ATP metabolite,
      stimulated cell proliferation in osteoblast-like cells (MC3T3-E1). ATP increased
      cytosolic Ca2+ due to Ca2+ mobilization from intracellular storage in the same
      concentration range of the nucleotide as that effective for DNA synthesis,
      suggesting the mediation of the phospholipase C/Ca2+ system in the mitogenic
      action. Since adenosine induced no Ca2+ mobilization, P2-purinergic receptor
      appears to be associated with ATP actions. The growth-promoting effect of ATP was
      not inhibited by H7, a protein kinase C inhibitor, and indomethacin, a
      cyclooxygenase inhibitor, indicating no involvement of activation of protein
      kinase C and production of prostaglandins in ATP-induced mitogenic signals.
      Either ATP or adenosine remarkably and synergistically potentiated platelet
      derived growth factor-induced DNA synthesis. These findings suggest that
      extracellular ATP and adenosine may play a physiological role in the regulation
      of bone formation.

PMID- 8998681
TI  - A randomized controlled trial of salmon calcitonin to prevent bone loss in
      corticosteroid-treated temporal arteritis and polymyalgia rheumatica.
AB  - Patients treated with high-dose or long-term corticosteroids are at risk of
      accelerated osteoporosis and spontaneous vertebral and traumatic fractures. To
      assess the efficacy of salmon calcitonin in preventing corticosteroid- induced
      osteoporosis, 48 patients with newly diagnosed polymyalgia rheumatica, temporal
      arteritis, and other vasculitides were enrolled in a 2-year, double-blind,
      randomized, controlled trial. Patients were randomized to receive subcutaneous
      injections t.i.w. of either 100 IU of salmon calcitonin (25 patients) or placebo
      (23 patients). After 2 years, 19 and 21 patients, respectively, were evaluable.
      All patients also received supplemental calcium carbonate (1500 mg daily in
      divided doses) and vitamin D3 (400 IU daily). Baseline and serial radiologic
      assessments included dual-energy X-ray absorptiometry (DXA) of the lumbar spine
      and hip, and spine radiographs to detect vertebral fractures. There were no
      significant baseline differences between the two study groups. The mean within
      subject percentage change in DXA lumbar spine density in the two groups over the
      2-year period of the study was only -0.1% (calcitonin plus calcium) versus -0.2%
      (placebo plus calcium) a nonsignificant difference despite the high mean
      cumulative corticosteroid doses of 5371 mg and 4680 mg, respectively (NS). The
      incidence of vertebral fracture was 12.5% (calcitonin plus calcium: 11%, versus
      placebo plus calcium: 14%, NS), with four fractures in the first year and one
      fracture in the second year. Higher cumulative cortico-steroid dose was
      associated with a greater loss in bone density. In rheumatic disease patients
      starting high-dose, long-term corticosteroids, salmon calcitonin with calcium and
      vitamin D3 provided no greater bone preservation than that observed with calcium
      and vitamin D3 alone.

PMID- 8998682
TI  - Stimulation of the growth of femoral trabecular bone in ovariectomized rats by
      the novel parathyroid hormone fragment, hPTH-(1-31)NH2 (Ostabolin).
AB  - The human parathyroid hormone, hPTH-(1-84), and its hPTH-(1-34) fragment are
      promising anabolic agents for treating osteoporosis because they can strongly
      stimulate the production of biomechanically effective cortical and trabecular
      bone in osteopenic ovariectomized (OVX) rats and trabecular bone in osteoporotic
      postmenopausal humans. The ideal PTH fragment for treating osteoporosis would be
      the smallest and functionally simplest fragment that activates only one signal
      mechanism and still strongly stimulates trabecular bone growth. A new PTH
      fragment, hPTH-(1-31)NH2, which only stimulates adenylyl cyclase instead of
      stimulating both adenylyl cyclase and phospholipase-C as do hPTH-(1-84) and hPTH
      (1-34), is this minimum, high-potency anabolic fragment. hPTH-(1-31)NH2 (which we
      have named Ostabolin) can greatly thicken trabeculae and increase the dry weight
      and calcium content of trabecular bone in the distal femurs of osteopenic, young,
      sexually mature OVX Sprague-Dawley rats when injected subcutaneously each day for
      6 weeks at doses between 0.4 and 1.6 nmole/100 g of body weight.

PMID- 8998684
TI  - Expression of the parathyroid hormone receptor and correlation with other
      osteoblastic parameters in fetal rat osteoblasts.
AB  - Primary fetal rat calvarial cell cultures were examined for the expression of
      different osteoblastic parameters at the single cell level and in the whole
      population. The presence of the parathyroid hormone (PTH) receptor was studied by
      employing receptor autoradiography. After 3 days of culture, 10% of the cells
      expressed the PTH receptor. Immunolocalization of osteocalcin in 3-day-old cell
      cultures was found to be strongly correlated with the presence of the PTH
      receptor. Alkaline phosphatase (APase) localization in 3-day-old cultures
      correlated with only 69% of the PTH receptor expressing cells. Our results show
      that in 3-day-old rat calvarial cell cultures, only about 10% of the cells show
      markers of osteoblastic differentiation. The presence of the PTH receptor is
      strongly correlated with the presence of osteocalcin, but less with the presence
      of APase, indicating that it is the mature osteoblast that expresses the PTH
      receptor. After 7 days of culture, most receptor labeling, APase, and osteocalcin
      expression was found in multilayered areas of cells (nodules).

PMID- 8998685
TI  - [Public health and the health of workers].

PMID- 8998683
TI  - Increase in femoral bone mass by ipriflavone alone and in combination with 1
      alpha-hydroxyvitamin D3 in growing rats with skeletal unloading.
AB  - We assessed the possibility that ipriflavone treatment might result in bone
      restoration in immobilized rats. We also investigated the effect of combined
      treatment with ipriflavone and vitamin D3 on the bone. Male Sprague-Dawley rats,
      6 weeks of age, were subjected to unilateral sciatic neurectomy. Three weeks
      after the operation, ipriflavone (100 mg/kg), 1 alpha-hydroxyvitamin D3 [1 alpha
      (OH)D3, 25 ng/kg], or both ipriflavone and 1 alpha (OH)D3 were orally
      administered every day for 12 or 24 weeks. After 12 weeks of treatment, only the
      group receiving combined treatment with ipriflavone and 1 alpha (OH)D3 showed
      increases in total femur calcium content (+16.4%, compared with the control).
      After 24 weeks, both animals treated with ipriflavone alone and those that had
      received the combination of ipriflavone and 1 alpha (OH)D3 showed significant
      increases in femur calcium content (+18.0% and +23.8%, respectively). In these
      treatment groups, X-ray analysis revealed an increase in bone mineral density
      over the entire length of the femur, and an increase in cortical diameter at the
      midshaft without affecting medullary width. Administration of 1 alpha (OH)D3 (25
      ng/kg) alone had no effect. Body weight, femur length, and serum markers of
      calcium and bone metabolism were not affected in any group. We evaluated the
      relationship between ipriflavone and vitamin D3 in bone cells in a culture system
      using rat bone marrow stromal cells in which the cells subsequently form
      mineralized bone-like tissue. Continuous treatment with ipriflavone (10(-5) M)
      for 21 days resulted in an increase in osteocalcin secretion, and enhanced its
      response to 1 alpha, 25-dihydroxyvitamin D3 (10(-11) M-10(-8 M)). These findings
      indicate that ipriflavone treatment increases the femoral bone mass in
      immobilized rats. In addition, a low dose of 1 alpha (OH)D3, which did not induce
      hypercalcemia, in combination with ipriflavone, augmented the stimulatory effect
      of ipriflavone alone on the bone mass, possibly due to a direct effect of each
      agent on osteoblastic cells.

PMID- 8998686
TI  - [Conflicts and ethical guidance in the relationship between health and work].
AB  - In recent decades, the main morals that affect the relationships between human
      work, the economy and health, have often obtained clear and authorized
      definitions. However, scientific breakthroughs, market forces, civil and penal
      laws and the ethical codes of the health profession, do not provide updated
      answers to the ethical problems that arise in many aspects of modern work. This
      article develops several types of conflict between interests and values. The
      conflict between the right to live, health and the safety of the workers, and the
      right of companies to "maximise" production. The conflicts that affect
      information: the rights of the workers to be aware of risks and hazards, the
      rights of the companies to industrial and commercial secrecy, the right and
      duties of professional experts. The conflicts between production and external
      environment, between workers and the population. The conflicts between workers
      themselves, and finally, the conflicts between work, reproductive health and
      reproduction of life.

PMID- 8998687
TI  - [Safety and health in work from the perspective of the Prevention of Occupational
      Hazards Act].
AB  - The passing of the Prevention of Occupational Hazards Act, (Ley 31/1995),
      constituted a change in direction in the development of occupational safety and
      health in Spain. This article describes the most salient points of this new
      legislation, from the criteria and principles that have to govern preventive
      activities, to the obligations and rights of both employers and workers, together
      with the co-operation and co-ordination of the activities of the various
      Administrations which have jurisdiction and the participation of employers' and
      workers' organisations, as the backbone of policy in matters concerning the
      prevention of occupational hazards.

PMID- 8998689
TI  - [The prevention and control of the risks with chemical products].
AB  - Increasing exposure to chemical products and substances could be affecting the
      changes that are being observed in the epidemiological pattern of illnesses. An
      estimation of the scale and seriousness of exposure, its effects and
      consequences, cannot be measured exclusively in terms of the classical indicators
      of mortality and morbidity. The prevention and control of risks associated with
      the use of chemical products requires a more integral approach, which studies the
      effects of chemical products in both the short- and long-term. A proposal is made
      for a "Risk Evaluation" strategy, based on the collection of exhaustive data, the
      estimation of response dosage, evaluation of exposure, identification of bio
      indicators and risk characterisation. Reference is made to both European and
      national legislation with regard to the question of classification and labelling
      of chemical products, specific risk phrases and cautionary advice, files on
      safety and classification data, in accordance with the specific effects on human
      health (substances whose effects are carcinogenic, mutagenic and toxic to
      reproduction). A description is provided of the main organisations devoted to the
      development and implementation of chemical risk prevention and control
      programmes. Finally, reference is made to the most relevant sources of
      information for consultation and studying chemical products.

PMID- 8998688
TI  - [Information and occupational health surveillance systems].
AB  - A lack of information about the risks and damage that workers are exposed to, is
      one of the most pressing problems for those who administrate, professional and
      social workers, and one which constitutes an obstacle to the defining of
      effective Occupational Health policies and plans. An analysis is carried out of
      the existing data sources in Spain, and a description is provided of the
      resources available for preventing occupational hazards. It is concluded that,
      with the possibilities that are offered by the new framework of standards, it
      will be possible to implement an Occupational Health Information System which
      will allow for determining priorities and reaching the objectives that have been
      set. Applying the laws and using the resources that are available will be
      sufficient.

PMID- 8998691
TI  - [The Instituto Navarro de Salud Laboral: an experience in collaboration between
      health and occupational jurisdictions].
AB  - BACKGROUND: Ever since 1986, when the first jurisdictional transfers took place
      from the State to Navarre in matters concerning occupational health and hygiene,
      the allocation of the different functions and means related to occupational
      health and the health structure has been an ongoing process. These activities
      were carried out from an overall health perspective, in the spirit of the General
      Health Act and the Local (Navarre) Health Act. Workers were viewed in a global
      way, no distinction being made between their work situation and the rest of their
      lives. That is why the Provincial Technical Bureau for Occupational Health and
      Hygiene was set up in 1986, followed by the Occupational Health Bureau, in 1988,
      as part of the Public Health Institute. THE NAVARRE OCCUPATIONAL HEALTH
      INSTITUTE: This was set up in 1993, under the responsibility of the Health
      Department. It incorporated the occupational health means which already existed
      in the Navarre Government. It was restructured in November 1995. The Departments
      of Health and Employment jointly control it, and collaboration between the two
      departments and other units, is the key factor. CONCLUSIONS: Experiences of over
      nine years, and especially the last three, have made it possible to guarantee
      that activities concerning occupational safety, hygiene and health do not depend
      to a greater or a lesser extent upon the spheres of either employment or health,
      but upon Public Administration in general, and the civil servants involved.
      Administrative coordination in such matters is of paramount importance.

PMID- 8998690
TI  - [The National Survey on Working Conditions: data for reflection].
AB  - This work presents some data of relevance from the National Survey on Working
      Conditions, carried out in Spain in 1993. A cross-section survey was undertaken
      on a representative sample of the industry and services sectors (3,148 workers),
      both through an individual interview which took place at their places of work,
      and a questionnaire. The study revealed that preventive activities are few and
      far between. Only 11.8% of the companies carried out surveys into the risk of
      occupational accidents and/or illnesses. This datum contrasts with the high
      incidence among workers of exposure to the risk of accidents (59%), noise (33%)
      or the inhaling of chemical substances (32%). Furthermore, approximately 50% of
      workers spend at least a quarter of their work time in a static posture or making
      repetitive hand-arm movements. It is estimated that 60% are exposed to high work
      rates or repetitive tasks of short duration. Where the question of morbidity is
      concerned, 60% of workers suffer from posture problems associated with their
      work. In this study, a comparison is made between these findings per activity
      sector, together with a detailed analysis of morbidity. Finally, it should be
      borne in mind, that the subjectivity in the responses and answers, which is
      inherent to any qualitative survey, should not be regarded as a negative aspect.
      The way in which the worker perceives and experiences his or her work
      environment, provides essential information for the preventionists.

PMID- 8998692
TI  - [Occupational health in the Autonomous Community of the Basque Country. OSALAN
      Instituto Vasco de Seguridad y Salud Laborales].
AB  - O.S.A.L.A.N.-Instituto Vasco de Seguridad y Salud Laborales is an autonomous
      administrative body depending on the Basque Government, ascribed to the Dept. of
      Justice, Economy, Work and Social Security, which is in charge of managing the
      general occupational health policies in the Autonomous Community of the Basque
      Country. Its objectives are: To promote an ongoing improvement in safety and
      occupational health for all the workers in the Basque Autonomous Region, through
      the management of programmes in matters affecting safety, hygiene, the
      environment and occupational health. To co-ordinate and concentrate the different
      activities related to occupational health, unifying and giving coherence to the
      functions which were previously the jurisdiction of different departments. Making
      companies aware of national and E.U. regulations, taking the measures that are
      set out by the European Directives and the Prevention of Occupational Hazards Act
      and the rest of the employment regulations, establishing the training and
      information channels required for promoting and applying these in the companies.
      It acts: from an overall perspective as regards the prevention of occupational
      hazards, thanks to co-ordination with all the disciplines involved, applying a
      multi-disciplinary treatment to the study of each and every one of the
      occupational hazard factors, which is aimed at the prevention of risks at their
      source. Providing companies with the ideal means for managing the safety and
      health of their workers. Promoting the implementation of systems which guarantee
      an ongoing improvement in occupational safety and health in the companies of the
      Basque Autonomous Region. Providing the technical and research support that makes
      it possible to tackle prevention efficiently. The provision established in the
      Creation Act (O.S.A.L.A.N.) should also be mentioned, as regards its application
      in public administration and the field of social economy, which was later
      endorsed and ratified through inclusion in the recent Prevention of Occupational
      Hazards Act.

PMID- 8998693
TI  - [Occupational health in the structure of public health. The experience of the
      Community of Valencia].
AB  - A description is provided of the Occupational Health activities developed and
      carried out in the Public Health Administration of the Health and Consumption
      Council in the Valencian Autonomous Region. Reference is made to the way these
      are integrated and to the different programmes that are brought into operation,
      together with the specific standard being applied.

PMID- 8998694
TI  - [The viewpoint of social workers on the future legislative framework for the
      prevention of occupational hazards].
AB  - The new Prevention of Occupational Hazards Act (P.O.H.A.) has aroused great
      expectation among social workers and health experts who are working in this
      field. This article contains a critical commentary of the above-mentioned Act.
      The conclusion is reached that the P.O.H.A. promotes safety and occupational
      health in work places: its aim is to improve working conditions; although it
      guarantees the participation of the social worker, it does not allow for co
      management in these matters; and that the deficiencies that are found must be
      overcome by means of the rulings, collective agreements and specific agreements
      with social workers.

PMID- 8998695
TI  - [Occupational health and the Prevention of Occupational Hazards Act].
AB  - A description is given of the main problems currently involved in matters
      concerning the prevention of occupational hazards, the basic contents of the
      recently passed Prevention of Occupational Hazards Act (Ley 31/1995), and the
      challenges that this law pose for the unions, employers, public administration,
      professionals in prevention and insurance companies for matters concerning
      occupational hazards and occupational illnesses.

PMID- 8998697
TI  - [Global changes and trends in work safety and health].
AB  - A description is given of the occupational health and safety problems which are
      common to workers all over the world, where these must be tackled with a view to
      achieving coherent and ongoing occupational safety for workers in their jobs.
      Occupational safety and health will continue to be priorities in international
      collaboration. Although the nature of the problems and solutions vary as a
      function of real priorities and needs, it is necessary to place greater emphasis
      on the application of overall activities concerning safety and health so that
      measures can be made and policies taken whose development is sustainable.
      International standards must be turned into actions on a national and company
      level with the active participation of social workers. The tripartite consensus
      will continue to be necessary for drawing up plans of action adapted to local
      situations, with a view to introducing improvements in work centres.

PMID- 8998696
TI  - [Company obligations in matters of occupational hazard prevention].
AB  - Using the conceptualization of the Prevention of Occupational Hazards Act as a
      basis, an analysis is carried out of company responsibilities in the question of
      preventing such hazards and in the development of the employment contract.
      Furthermore, emphasis is placed on terminology difficulties with respect to
      concepts, legal matters and materials, in the application of the Act.

PMID- 8998698
TI  - [Pregnancy and contraception in the diabetic woman. Gestational diabetes.
      Recommendations of ALFEDIAM (French Language Association for the Study of
      Diabetes and Metabolic Diseases)].

PMID- 8998699
TI  - [The night of the insulin-dependent diabetic patient. Recommendations of ALFEDIAM
      (French Language Association for the Study of Diabetes and Metabolic Diseases)].

PMID- 8998700
TI  - [A symbol without "head" (testa=head). Antonio Giuseppe Testa].

PMID- 8998701
TI  - [Cardiovascular toxic effects of drugs not used in cardiology].

PMID- 8998702
TI  - [Radiation-induced coronary disease].

PMID- 8998703
TI  - [Coronary disease in heart transplantation].

PMID- 8998704
TI  - [Role of neutrophil granulocytes and platelets in the pathology of
      microcirculation].

PMID- 8998705
TI  - [Clinical efficacy of oral dopaminergic agents: new findings].

PMID- 8998706
TI  - [Refractory heart failure: it requires the use of polychemotherapy. What is the
      rationale?].

PMID- 8998708
TI  - [Thyrotoxicosis and the cardiovascular system].

PMID- 8998707
TI  - [Cardiovascular system physiopathology in thyroid dysfunction].

PMID- 8998710
TI  - [Coronary patency and functional recovery in post-infarction].

PMID- 8998709
TI  - [The heart and hypothyroidism].

PMID- 8998711
TI  - [Amiodarone and the thyroid].

PMID- 8998712
TI  - [History of the pharmacologic therapy of arterial hypertension: from diuretics to
      angiotensin II receptor antagonists].

PMID- 8998713
TI  - [Gradual reduction of arterial pressure and 24-hour blood pressure control as
      objective of antihypertensive therapy].

PMID- 8998715
TI  - [Comparison of provocation tests based on physiopathologic mechanisms:
      suggestions for the clinician].

PMID- 8998714
TI  - [The first clinical experience in Italy with angiotensin II receptor antagonists:
      results of a multicenter study on the efficacy and tolerance in arterial
      hypertension].

PMID- 8998716
TI  - [The use of stress echocardiography in the assessment of myocardial viability].

PMID- 8998717
TI  - [Microcirculation integrity, contractility reserve, and myocardial functional
      recovery in post-infarction].

PMID- 8998718
TI  - [Prognostic stratification after acute myocardial infarction: usefulness and
      limitations of echocardiography in stress].

PMID- 8998719
TI  - [The use of stress echocardiography in the assessment of results of myocardial
      revascularizations interventions].

PMID- 8998720
TI  - [Risk factors and coronary disease].

PMID- 8998721
TI  - [Plurimetabolic syndrome: association of diabetes, dyslipidemia, and arterial
      hypertension].

PMID- 8998722
TI  - [Arterial hypertension, sympathetic nervous system, and organ lesion].

PMID- 8998723
TI  - [Effect of antihypertensive treatment on the clinical course of coronary
      disease].

PMID- 8998724
TI  - [Physiopathological mechanisms in the natural history of the atherosclerotic
      plaque].

PMID- 8998725
TI  - [Risk factors, ageing, and asymptomatic carotid plaque].

PMID- 8998726
TI  - [Progression and regression of the plaque: comparison of diagnostic methods].

PMID- 8998728
TI  - [Regression of the plaque after prolonged pharmacologic treatment].

PMID- 8998727
TI  - [Usefulness of Doppler color ultrasonography for the non-invasive diagnosis of
      the atherosclerotic plaque].

PMID- 8998729
TI  - [A new cardiovascular risk factor: heart rate].

PMID- 8998730
TI  - [Myocardial infarction: beyond thrombolysis].

PMID- 8998731
TI  - [Mitral valve insufficiency: physiopathology and best timing for surgery].

PMID- 8998732
TI  - [Mitral insufficiency: surgical treatment].

PMID- 8998733
TI  - [Aortic insufficiency: physiopathology and the best timing for surgery].

PMID- 8998734
TI  - [Surgical treatment of aortic valve insufficiency].

PMID- 8998736
TI  - [Current applications and perspectives of thrombolytic therapy in peripheral
      arterial diseases and deep venous thrombosis].

PMID- 8998735
TI  - [Rationale for metabolic treatment of left ventricular dysfunction].

PMID- 8998737
TI  - [Current applications and perspectives of thrombolysis in acute cerebral
      ischemia].

PMID- 8998738
TI  - [Diastolic filling and the law of Frank-Starling].

PMID- 8998739
TI  - [The problem of diastolic dysfunction in dilated cardiomyopathy and hypertrophic
      cardiomyopathy].

PMID- 8998740
TI  - [Methods for assessing ventricular relaxation and filling].

PMID- 8998741
TI  - [Ventricular relaxation and refilling in myocardial stunning].

PMID- 8998742
TI  - [Angioscopy in the diagnostic imaging of acute coronary syndrome].

PMID- 8998743
TI  - [Inflammatory mechanisms associated with acute coronary syndrome].

PMID- 8998744
TI  - [Medical treatment of acute coronary syndrome].

PMID- 8998745
TI  - [Invasive treatment of acute coronary syndrome].

PMID- 8998746
TI  - [Dilatation of congenital aortic stenosis].

PMID- 8998747
TI  - [L-carnitine in the treatment of left ventricular dysfunction in post
      infarction].

PMID- 8998748
TI  - [Intravascular stents in the treatment of congenital cardiopathy].

PMID- 8998749
TI  - [Risk stratification in patients after acute myocardial infarction].

PMID- 8998750
TI  - [Clinical studies of the effectiveness of aspirin in the prevention of major
      cardio-cerebrovascular occurrences].

PMID- 8998751
TI  - [Prevention of coronary events. What we know and what we do].

PMID- 8998752
TI  - [Pharmaco-economic assessment of strategies for the prevention of cardiovascular
      events].

PMID- 8998753
TI  - [From overload to contractile deficiency in valvular cardiopathy].

PMID- 8998755
TI  - [Identification of viable myocardium in candidates for transplantation].

PMID- 8998754
TI  - [Metabolism and function of peripheral muscles in heart failure: pharmacologic
      effects].

PMID- 8998756
TI  - [Assessment of contractile reserve in dilated cardiomyopathy].

PMID- 8998757
TI  - [Echocardiography in the assessment of the patient with heart insufficiency:
      assessment parameters of the pharmacologic treatment].

PMID- 8998758
TI  - [Echocardiography in the assessment of thromboembolic risk in patients with heart
      insufficiency].

PMID- 8998759
TI  - [Echocardiography versus catheterization in the selection of patients for heart
      transplantation].

PMID- 8998760
TI  - [Computerization of cardiologic departments].

PMID- 8998761
TI  - [A databank at a cardiology department: various tips].

PMID- 8998762
TI  - [Computerized assessment of electric heart signals and cardiovascular images].

PMID- 8998763
TI  - [Expert systems in cardiology: possibilities, limitations, and perspectives].

PMID- 8998764
TI  - [Physiopathology of coronary insufficiency].

PMID- 8998766
TI  - [The concept of total ischemic burden: clinical significance].

PMID- 8998765
TI  - [Endothelium and regulation of vascular function].

PMID- 8998767
TI  - [Changes in total ischemic burden and ischemic threshold].

PMID- 8998768
TI  - [Improvement of the prognosis in ischemic cardiopathy: cause and effect on the
      prognostic value of tests].

PMID- 8998769
TI  - [Prospects of pharmacologic treatment of post-ischemic heart failure].

PMID- 8998770
TI  - [Left ventricular dysfunction in ischemic cardiopathy: physiopathology and
      therapeutic rationale].

PMID- 8998771
TI  - [Chronic thromboembolic pulmonary hypertension].

PMID- 8998772
TI  - [Chronic thromboembolic pulmonary hypertension. Non-invasive diagnosis].

PMID- 8998773
TI  - [Chronic thromboembolic pulmonary hypertension. Invasive diagnosis].

PMID- 8998774
TI  - [Pulmonary thromboendarterectomy in the surgical treatment of chronic
      thromboembolic pulmonary hypertension. First Italian experience].

PMID- 8998775
TI  - [Post-embolic pulmonary arterial hypertension: therapeutic indications].

PMID- 8998776
TI  - [Postischemic changes in the permeability of coronary microcirculation and
      ventricular remodeling].

PMID- 8998777
TI  - [Transesophageal and intravascular echocardiographic imaging in aortic
      dissection].

PMID- 8998778
TI  - [Imaging techniques in aortic dissection. Diagnosis with angiography].

PMID- 8998779
TI  - [Computerized tomography and magnetic resonance in the study of aortic
      dissection].

PMID- 8998781
TI  - [Role of the general physician in cardiology care].

PMID- 8998780
TI  - [Diagnostic techniques useful to surgical treatment].

PMID- 8998782
TI  - [Point of view of the cardiologist working outside the hospital].

PMID- 8998783
TI  - [Point of view of the hospital cardiologist on the role of the physician working
      outside the hospital in cardiology care].

PMID- 8998784
TI  - [Sarcoplasmic reticulum function in ischemic cardiopathy].

PMID- 8998785
TI  - [Myocardial protection from ischemic damage: effects of preconditioning and
      pharmacologic activation of KATP channels].

PMID- 8998786
TI  - [Electrophysiologic features of the modulation of ATP-dependent potassium
      channels].

PMID- 8998787
TI  - [Potassium channel activators: hemodynamic effects at the systemic and coronary
      level].

PMID- 8998788
TI  - [Clinical use of potassium channel activators in angina pectoris: efficacy and
      tolerance].

PMID- 8998789
TI  - [Extracardiovascular toxic effects of drugs used in cardiology].

PMID- 8998790
TI  - IOM study on nursing staffing falls short says ANA: expresses disappointment over
      scope of recommendations.

PMID- 8998791
TI  - Fourth U.N. Conference for Women in Beijing. Interview by Susan Sanford.

PMID- 8998792
TI  - Nursing alert--cryptosporidiosis.

PMID- 8998794
TI  - Hepatitis C: an emerging threat.

PMID- 8998793
TI  - Joint Commission accreditation--relationship to nursing.

PMID- 8998795
TI  - The Colorado Nurse Practice Act: a historical perspective.

PMID- 8998796
TI  - [Is homeopathic therapy more effective that placebos?].
AB  - A critical report is presented on the reliability of two clinical trials by
      Reilly et al. (Lancet, 1986ii, pp. 881-886 and 1994ii, pp. 1601-1606) who has
      claimed that the effect of homeopathy differs significantly from placebo.
      Biophysical hypothesis dealing with the intriguing problem of the mechanism of
      action of homeopathic remedies are also reviewed in this paper.

PMID- 8998797
TI  - [Sepsis. I. [Definition of the concept and comments on pathophysiology].
AB  - During the past five years a marked development occurred as regards knowledge on
      sepsis and its complications. A new term was introduced-SIRS (systemic
      inflammatory response syndrome). Two substantial changes pertain to the following
      facts. First the clinical picture of sepsis need not be due only to infection,
      and the patient is not an innocent victim of infection, but the organ damage is
      the results of the patient's active fight with the inducing cause. The authors
      review recent views regarding the pathophysiology of sepsis.

PMID- 8998798
TI  - [Transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of
      symptomatic portal hypertension].
AB  - BACKGROUND: A transjugular intrahepatic portosystemic shunt (TIPS) is the
      creation of a percutaneous portosystemic anastomosis which is used as an
      alternative method of surgical portosystemic shunts and endoscopic treatment in
      the therapy of complications of portal hypertension. The objective of the present
      work was to summarize experience with TIPS in 100 patients. METHODS AND RESULTS:
      In 1992-1995 the authors treated 100 patients with symptomatic portal
      hypertension by TIPS. To create the shunt in 84% patients a spiral Z stent was
      used, in the remainder a Wallstent. In 86% patients the indication for TIPS was
      haemorrhage associated with portal hypertension and in 14% refractory ascites.
      TIPS was implemented in 98% patients. The pressure in the portal vela was not
      reduced on average to 58% of the original value. Haemorrhage was not stopped in
      one of 7 patients. Haemorrhage from varices reappeared in 7% patients indicated
      on account of repeated haemorrhage and was always associated with the finding of
      chronic stenosis of the shunt. The mortality in conjunction with the procedure
      was 4%, the mortality within 30 days after operation was 8%. Uncontrollable
      encephalopathy developed in 3% of the patients. Primary patency of the shunt
      created by the spiral Z stent was 85% after 6 months, after 12 months 72% and
      thus does not differ from primary patency when Wallstents are used, as reported
      in the literature. CONCLUSIONS: TIPS is an effective method to reduce the
      pressure in the portal vein in portal hypertension. The main limiting factor of
      the method is stenosis of the shunt due to hyperplasia of the neointima. Stenoses
      of the shunt can be effectively dilated by percutaneous balloon angioplasty.

PMID- 8998799
TI  - [Is the recent decrease in cholesterolemia in the Czech Republic convincing
      evidence?].
AB  - BACKGROUND: The objective of the study was to evaluate the 8-year trend of serum
      cholesterol levels in six districts of the Czech Republic, to assess whether the
      reduction of mean values of total cholesterol recorded during the period between
      1985 and 1992 was convincing and to discuss possible causes and consequences of
      this development. METHODS AND RESULTS: Three cross-sectional surveys of risk
      factors were implemented in independent random 1% samples of the population aged
      25-64 years. In 1985 1256 men (respondence rate 81.5%) and 1317 women (85%) were
      examined, In 1988 1357 men (85.2%) and 1412 women (88.4%), in 1992 1142 men
      (73.2%) and 1211 women (76.7%). A detailed check of the deviations in estimations
      during different time intervals from reference values provided evidence that the
      analytical method did not have an impact on the revealed changes. In men the mean
      total cholesterol level was 6.21 (95% confidence limit 6.14-6.28 mmol/l in 1985;
      6.29 (6.23-6.35) mmol/l in 1988; 5.99 (5.91-6.06) mmol/l in 1992. In women the
      mean value of the total cholesterol level was 6.19 (6.12-6.25) mmol/l in 1985;
      6.23 (6.17-6.30) mmol/l in 1988; 5.95 (5.88-6.02) mmol/l in 1992. According to
      variance analysis (ANOVA) the serum cholesterol in 1992 was lower by 0.22 mmol/l
      (p < 0.0001) than in 1985 and by 0.28 mmol/l (p < 0.0001) lower than in 1988. The
      drop of cholesterol between 1988-1992 may have been caused by dietary changes
      recorded in the population. According to nationwide data after 1990 there was a
      marked drop of the consumption of meat and meat products, milk and dairy products
      and animal fats, while the consumption of vegetable fats increased. Despite these
      dietary improvements, in six districts in 1992 fats accounted for 37% of the
      energy intake, the P/S ratio was only 0.41 in men and 0.46 in women. In these
      districts in 1992 and 1993 a decline of the standardized mortality rate from IHD
      in men was recorded. CONCLUSIONS: During an eight-year period the mean serum
      cholesterol level of men and women decreased significantly in six districts of
      the Czech Republic. This change was probably associated with a restricted intake
      of foods which have an impact on the serum cholesterol level.

PMID- 8998800
TI  - [Large-scale isolation of islets of Langerhans in dogs and human].
AB  - BACKGROUND: Transplantation of isolated islets of Langerhans is a perspective
      method of treating type 1 diabetes. The first prerequisite for its implementation
      is to obtain sufficient amounts of vital islets. The objective to the authors'
      experiments was to introduce a method of massive isolation of islets of
      Langerhans from dogs which would serve as a model pro obtaining islets of
      Langerhans from humans and would permit to use them in future in clinical
      practice. METHODS AND RESULTS: After excision of the dog pancreas the authors
      injected into the ducts a 1% collagenase solution and the tissue was deposited in
      a specially developed semi-automatic isolation system which consisted of a
      vibrating isolation chamber in which an isolation solution with controlled
      temperature circulated. As soon as the islets started to be released, the system
      was cooled and the disintegrated tissue was collected. The islets were separated
      from the acinar mass by centrifuging in a ficoll mass gradient. The islet
      function was tested by transplantation to athymic diabetic mice. A total of 15
      isolations of dog islets was performed, incl. 5 which were evaluated
      quantitatively. In a similar way twice isolation from a human cadaverous pancreas
      was implemented. On average 6336 +/- 745 (+/-SD) purified dog islets were
      obtained. Their function was tested by normalization of the blood sugar after
      transplantation to diabetic mice. The authors obtained also vital highly purified
      human islets. CONCLUSIONS: The authors developed a method of isolation of dog and
      human islets of Langerhans which makes it possible to obtain sufficient amounts
      of vital islet tissue which could be used for transplantation. A further task
      will be to standardize the process and adjust it to hygienic norms essential for
      clinical use.

PMID- 8998801
TI  - [Magnesium, its role and metabolism].
AB  - Magnesium (Mg) is the fourth most abundant cation in the human body and is second
      only to potassium in intracellular metabolism. Magnesium deficiency results in
      biochemical, neuromuscular and cardiovascular changes. This review deals with
      both normal and abnormal Mg metabolism.

PMID- 8998802
TI  - [PCR--polymerase chain reaction. Principles and applications in research and
      medical practice].
AB  - At present, PCR (polymerase chain reaction), is the method most often used in
      molecular genetics. The aimed amplification of the short DNA chain is reached by
      three cyclically repeated steps using different temperatures. The reaction
      demands the presence of DNA polymerase, buffer, dNTP as basic elements of DNA and
      a pair of short oligonucleotides, which makes the reaction specific. The product
      of reaction is usually analysed using electrophoresis in agarose gel or
      polyacrylamide gel and visualised by ethidium bromide.

PMID- 8998803
TI  - [Sepsis. II. Complications and treatment of sepsis].
AB  - Sepsis and its complications are serious medical problem of intensive medicine.
      Therefore recently several therapeutic procedures were tested in sepsis and its
      complications such as syndrome of multiorgan dysfunction or septic shock. The
      authors review possibilities how to treat these complications.

PMID- 8998804
TI  - [3 years of long-term home oxygen therapy in the Czech Republic].
AB  - BACKGROUND: Long-term domiciliary oxygen therapy was introduced in the Czech
      Republic as a standard therapeutic method in patients with chronic respiratory
      failure in October 1992. As a source of oxygen almost exclusively oxygen
      concentrators are used which are allocated to the patients according to criteria
      elaborated by the European Respiratory Society. METHODS AND RESULTS: From October
      1, 1992 to October 1, 1995 the mean number of installed concentrators is
      10,24/100000 population. From a total of 1064 patients by October 1, 1995 3.8%
      were treated for three years, 20.7% for two years and 34.4% for more than one
      year. In the course of three years a total of 490 patients died. The mean
      survival period of patients treated for prolonged periods by domiciliary oxygen
      therapy was 8.88 months. The high mortality rate is due to the fact that patients
      in a very serious state are treated. On account of chronic pulmonary disease
      oxygen therapy was indicated in 93.4%, on account of interstitial pulmonary
      processes (KFA and other fibroses) in 3.9, on account of kyphoscoliosis in 2.4%
      and on account of cystic fibrosis in 0.3% of the group. The mean costs of
      treatment were 114.40 Ke/day which is a third of the costs when the patient is
      hospitalized. CONCLUSIONS: Domiciliary oxygen therapy proved effective and
      economical in patients with chronic respiratory failure.

PMID- 8998806
TI  - [Diagnostic certainty of lymph node biopsy in malignancies].
AB  - Bioptic diagnosis of malignant processes in lymph nodes is a difficult method and
      is less accurate than sometimes expected. After transfer of haematological
      patients-as a rule to provide specialized treatment-a diagnostic baseline
      examination of biopsy is useful. The clinician procures for this "second reading"
      all basic data to improve the diagnostic certainty and deserves support. A
      controversial character of the assembled data is not associated with any
      specially or professional skill. It ensues, however, from the general principle
      of good care of the patient. In oncology a "second reading" is not a novelty. It
      is a recommended approach during typing according to the international
      classification of oncological diseases. Assessment of certainty (C factor) is
      moreover included in assessment of the grade of malignity in the TNM system.

PMID- 8998805
TI  - [False-negative native CT findings in the development of cerebral ischemia].
AB  - BACKGROUND: The "fogging effect" in the native CT picture of the brain masks in
      case of a cerebrovascular attack the pathological finding of hypodensity by
      creating a neovascular net necessary for the clearing activity of macrophages.
      METHODS AND RESULTS: The "fogging effect" was diagnosed on CT and monitored as a
      transient finding in a patient after a cerebrovascular attack. The submitted
      paper analyzes in detail and explains the dynamically developing clinical
      symptomatology of the patient. CONCLUSIONS: The "fogging effect" can be the
      source of erroneous clinical interpretation of a CT finding. It is important to
      know about its existence, and in case of diagnostic doubts, consider the i.v.
      administration of a contrast substance even though the perfusion may temporarily
      deteriorate. Visualization of an ischaemic focus by contrast provides unequivocal
      evidence of the extent and site of malacia.

PMID- 8998807
TI  - [Control mechanisms of cell transition from the G1 phase to the S phase--the R
      point].
AB  - The critical moment of regulation when transition of the cell from the G1 to the
      S phase takes which is decisive for its division is the so-called R-point
      (restriction point). The disorder of molecular mechanisms controlling the passage
      of the cell through this site is an associated manifestation of most tumourous
      processes. A considerable part of this mechanism is the RB protein, binding
      transcription factors needed for the activation of genes effective in the S
      phase. Its binding capacity depends on the extent of phosphorylation and on the
      activity of the appropriate kinases and their inhibitors.

PMID- 8998808
TI  - [Request for lectures on gerontology in 1843].

PMID- 8998809
TI  - [Intelligence and intelligence tests].
AB  - In psychology, the term intelligence has been introduced for the description of
      the certain, theoretically postulated complex of psychical events (thinking,
      attention, imagination, memory etc.). Intelligence belongs to the category of
      personality features, to its attributes. It has certain structure, which has been
      shown from the viewpoint of ontogeny, to be dynamical during the development of
      the individual. Intelligence testing belongs to one of the oldest
      psychodiagnostic methods used to measure not only ones mental abilities, but also
      the current individual mental level. This is the reason why careful
      interpretation of its results is always so crucial. Mentioned are examples of
      some of these tests, its interpretation, quality and proficiency. Discussed are
      also questions of the diagnostic usefulness of these tests.

PMID- 8998810
TI  - [Tuberculosis in the Czech Republic in 1994. Does compulsory notification give a
      true picture of tuberculosis morbidity?].
AB  - In the Czech Republic in 1994 a total of 1960 new cases of TB of all forms and
      localizations were notified, i.e. 19.0 patients per 100,000 population. This
      number comprised 1644 cases of TB of the respiratory system (15.2 patients/100
      000 population). Bacteriological tests were made in 1058 new cases of respiratory
      TB (10.2/100,000, whereby in 524 patients in sputum acid resistant rods were
      detected under the microscope. Extrapulmonary forms accounted for 16% of all
      notified cases of TB and relapses of TB accounted for less than 3% of the total
      number of notified cases. The TB mortality varied near 0.8 deaths/100,000
      population. These numbers did not differ significantly from data for 1992 and
      1993 and it may be concluded that the stagnating trend of tuberculosis in this
      country persists. The notified data made it possible to create a set of direct
      and indirect epidemiological indicators (age distribution, notifications,
      prevalence of severe forms, regional distribution, mortality rate and comparison
      of hospital admission on account of TB), which helped to show that the validity
      of notification has not changed much in recent years. The data assembled in
      notifications can therefore be used for comparative studies and they can be
      considered a measure of the TB morbidity. However, every evaluation of morbidity
      based on notification cells for verification of the validity of the presented
      data.

PMID- 8998811
TI  - [Early diagnosis of impaired glomerular and renal tubule function in patients
      with acromegaly].
AB  - BACKGROUND: Albuminuria (A), increased urinary excretion of glycosaminoglycans
      (GAG) and increased activity of N-acetyl-beta-glucosaminidase (NAG) in urine are
      early markers of glomerular and tubular changes in various pathological
      conditions at a time when renal functions do not yet display impaired function
      and when the changes are still reversible. The objective of the presented study
      was to assess to what extent these early changes may play a part in acromegaly.
      METHODS AND RESULTS: In a group of 24 acromegalic patients and in 18 healthy
      controls the authors examined the microalbuminuria (RIA Immunotech Prague),
      urinary excretion of glycosaminoglycans (spectrophotometrically by the carbazole
      method) and they assessed the NAG activity in urine (spectrophotometrically). In
      acromegalic patients before surgical and pharmacological treatment the authors
      found, as compared with healthy controls, increased urinary excretion of GAG [4.4
      (0.9-22.7) g/mol creat. vs. 2.1 (0.8-5.5) g/mol creat, p < or = 0.001], elevated
      albuminuria [3.6 (0.3-37.4) g/mol creat. vs. 0.5 (0.1-2.2) g/mol creat, p < or =
      0.001 and an enhanced NAG activity [1005 (345-2935) U/l vs. 470 (195-1135) U/l, p
      < or = 0.001]. The parameters of albuminuria and urinary GAG excretion
      characterize rather glomerular renal function, they correlate mutually (r = 0.64
      p < or = 0.001), while the urinary NAG activity, depending on tubular function,
      does not correlate with them. No correlation of these parameters with the IGI
      concentration (for A: 0.3, for GAG: -0.04 and for NAG: -0.02 according to Pearson
      was found. CONCLUSIONS: In hormonally active acromegalic patients without
      apparent altered renal functions (normal serum creatinine, Albustix negative) the
      authors detected early changes of glomerular and tubular functions. They found a
      significant correction between albuminuria and GAG excretion.

PMID- 8998812
TI  - [Effect of temperature on rheologic properties of blood and internal viscosity of
      erythrocytes].
AB  - BACKGROUND: The blood viscosity is one of the factors affecting tissue blood
      flow. Aim of the study was to establish how the blood viscosity and internal
      viscosity of the red cell (Tk) may be influenced by change of the temperature.
      METHODS AND RESULTS: We have measured plasma and blood viscosity in 20 samples of
      human plasma and 17 samples of human blood. Viscosity was established with
      rotational viscometer under the temperature ranging from 25 degrees C to 45
      degrees C. Concomitantly the internal viscosity of the red cell (Tk) was
      estimated. Plasma and blood viscosities are decreasing with the temperature
      elevation but the change is not linear through temperature range used for
      testing. The most pronounced change was found in relatively lower temperatures.
      Relative viscosity of the blood did not change significantly with the temperature
      except of measurements under low shear conditions performed in low temperature.
      Relative blood viscosity increased with temperature fall in such a situation. The
      internal viscosity of the red cell (Tk) increased significantly with temperature
      elevation. CONCLUSIONS: The average values of the blood and plasma viscosity fell
      with temperature elevation but the change was not linear. The plasma viscosity
      change was the highest in the low temperature range. These findings together with
      significant differences between relative and dynamic blood viscosity in low shear
      conditions and in 25 degrees C showed that blood viscosity was influenced by
      qualitative changes of the plasma followed by higher aggregation of the red
      cells.

PMID- 8998813
TI  - [A continent urinary diversion with a detubularized rectum and sigmoid (sigmo
      rectal pouch)].
AB  - BACKGROUND: The continent reservoir is an ideal urinary diversion in patients
      after cystectomy. The artificial closing mechanism construction in these
      reservoirs is rather complicated and the results are uncertain. The objective of
      the present work is to assess own experience with a relatively simple
      rectosigmoid reservoir created by a method described by M. Fisch. METHODS AND
      RESULTS: Since 1992 till 1995 the sigma-rectum detubularized reservoir was
      performed in 30 patients. The intricating bladder cancer was an indication for
      the operation in 27 patients and the other bladder diseases in 3 patients. The
      patients age ranged from 18 to 75 years. Diurnal continence was achieved in all
      30 patients. 12 of them have to awake during the night to evacuate the reservoir
      1 to 3 times. CONCLUSIONS: Sigma-rectum pouch is a good form of cintinent
      diversion in such patient, which are not suitable for orthoscopic neobladder
      because of oncologic limitation or bad general conditions. The patients tolerate
      the procedure very well, heal and adapt quickly to new evacuating mechanisms.

PMID- 8998814
TI  - [Familial juvenile gouty nephropathy].
AB  - The authors present the description of a family comprising father (his mother had
      died middle-aged from renal failure) and his two children aged 15 and 17 years
      who developed is young age (already in the second decade) gouty arthritis and
      primary interstitial nephritis. Based on the laboratory finding of hyperuricaemia
      with disproportionately low urate excretion and excretion of excessive uric acid
      formation, an enzyme defect and other renal disease the authors diagnosed
      familial gouty juvenile nephropathy. This diagnosis was confirmed also by
      histological examination of renal biopsy in the youngest member of the family. It
      is a disease which belongs into the group of hereditary types of nephritis. In
      the literature worldwide some nine families were described, in the Czech Republic
      it is the first description of this condition.

PMID- 8998815
TI  - [Phthalic acid esters and the human body].
AB  - Phthalic acid esters have been used for its softening and plastification effects
      as additives to various kinds of products: colours, paintings, glues, cosmetic
      products, inks, repellents, films, PVC-derived products including medical
      disposable PVC products. The authors present a basic review of literature on
      toxicologically important sources including medical disposable products. They
      refer about the deleterious effects on the mammalian organism, possibilities to
      replace phthalic acid esters by other softening and plasticizing remedies as well
      as the use of such kinds of materials, which do not require these additives.

PMID- 8998816
TI  - [Determination of ACTH in the inferior petrosal sinuses in the examination of
      patients with hypercortisolism].
AB  - BACKGROUND: Differential diagnosis of the etiology of ACTH-dependent
      hypercortisolism is very difficult in some cases. The uncertainty, whether there
      is a central or ectopic etiology, is also strengthened by the fact that even
      nuclear magnetic resonance (MR) sometimes does not prove the pituitary adenoma. A
      more precise differential diagnosis under these conditions has been made, over
      the last years, by selective determination of ACTH levels bilaterally in sinus
      petrosi inferiores (SPI) and by their comparison with the level in peripheral
      blood. The confirmation of central etiology makes a decision about neurosurgical
      intervention easier. This intervention, due to the present microsurgery
      technique, makes it possible to detect otherwise undetectable microadenoma and
      enables its selective excision with maintaining healthy hypophysis tissue and all
      its functions. METHODS AND RESULTS: In the last two years the authors indicated
      11 patients (10 women, one man at the age of 17-54 years, mean age 33.5 year)
      with proved ACTH-dependent hypercortisolism to the determination of ACTH in SPI.
      Their CT or NMR examination did not prove a hypophysis tumour unequivocally. Only
      in one female patient the catheterization was not possible for anomalous vascular
      bed with aplasia of internal jugular vein on the left and hypoplasia of internal
      jugular vein on the right. In 8 patients the determination of the ratio of ACTH
      levels between SPI and periphery (7.78 +/- 1.54, mean +/- S.E.) has shown that
      even the basal levels indicated central etiology of hypercortisolism. This has
      been confirmed by the ratio of the values of ACTH after stimulation with
      corticotrophin releasing hormone (CRH). The diagnosis was confirmed in all
      patients by surgery, by histology and post-operation course. In two female
      patients the ratio of basal levels of ACTH, SPI/periphery did not prove useful
      for the diagnosis of the Cushing's disease. In the first patient the CRH
      stimulation was not yet performed routinely and the ratio of basal levels of
      ACTH, SPI/periphery gave a false negative result, as shown by the finding of
      adenoma of hypophysis during the operation. The operation was indicated on the
      basis of hormonal examinations and repeated MR with a finding of suspected
      microadenoma and the diagnosis was then confirmed by further clinical
      development. The determination of the levels of ACTH after CRH stimulation would
      give more precision in this case, as shown by analysis of the results of large
      cohorts in literature, which we perform at present as well. In the other patient
      the CRH stimulation test was done, changing the ratio from 1.1 to 5.7 and thus
      confirmed central etiology of the Cushing's syndrome. In agreement with
      literature this method did not contribute to lateral localization of the tumour.
      CONCLUSIONS: The determination of basal levels of ACTH in SPI and levels after
      CRH stimulation enables to differentiate between central and ectopic
      overproduction of ACTH in the ACTH-dependent Cushing's syndrome.

PMID- 8998817
TI  - [Vasoactive factors in chronic glomerulonephritis].
AB  - BACKGROUND: The kidney damage in chronic glomerulonephritis develops not only as
      a result of causal immunopathological evens, but also due to chronic adaptation
      changes. The study was aimed at identification of active agents, which can serve
      as markers of proceeding adaptation changes and to determine, if these changes
      may be determined in patients undergoing the stage of remission of chronic
      glomerulonephritis. METHODS AND RESULTS: The authors determined renin activity,
      concentration of atrium natriuretic peptide and endothelin in plasma and
      elimination of some prostanoids in urine in 33 patients with chronic stabilized
      glomerulonephritis with normal glomerular filtration and with normal blood
      pressure and in 21 healthy subjects. Seventeen patients without proteinuria did
      not receive therapy, 16 patients with minute proteinuria received 100 mg of
      acetylosalicylic acid daily. In the untreated patients without proteinuria, the
      elimination of thromboxane in urine was significantly higher than in both other
      groups. The plasma level of atrium natriuretic peptide in all 33 patients was
      significantly lower than in the healthy persons. CONCLUSIONS: Based on this study
      the authors believe that adaptation changes proceed even in patients with chronic
      glomerulonephritis in clinical remission. The increased production of renal
      thromboxane, which can be successfully blocked by acetylosalicylic acid may be
      the marker of glomerular changes. A decreased level of atrium natriuretic peptide
      could reflect tubulointerstitial changes.

PMID- 8998818
TI  - [Antioxidants and malondialdehyde during hemodialysis with cellulose diacetate
      and polysulfone membranes].
AB  - BACKGROUND: Free radicals (FR) may cause lipid peroxidation and damage
      macromolecules and cellular structure of the organism, e.g. endothelium and
      erythrocytes. Some studies have shown that haemodialysis is connected with
      increased FR production. The aim of the study was to evaluate the effects of two
      dialysis membranes on lipid peroxidation and some antioxidant protective factors.
      METHODS AND RESULTS: The authors followed nine patients treated in a regular
      dialysis programme. In a cross controlled study the patients underwent
      haemodialysis with the use of cellulose diacetate (CDA) and polysulfone (PS)
      dialysis apparatus. Malondialdehyde in plasma was determined as a marker of lipid
      peroxidation. The haemodialysis with CDA or PS did not result in increased
      malondialdehyde levels in min. 30 or at the end of the procedure. The antioxidant
      capacity of plasma decreased after haemodialysis in a similar way with both types
      of membranes (PS, 1.67 +/- 0.10 mumol/l versus 1.47 +/- 0.23, P < 0.05; CDA: 1.72
      +/- 0.10 versus 1.55 +/- 0.12, P < 0.05). The selenium blood level did not
      change. Activity of glutathione peroxidase (GSHPx) in blood before the dialysis
      was higher in the observation with subsequent use of CDA than while using PS
      (38.6 +/- 9.4 versus 34.5 +/- 6.6, P < 0.05). In the cohort with polysulfone
      membrane GSHPx further decreased in min. 30 of haemodialysis (34.0 +/- 6.6 IU/g
      Hb versus 31.1 +/- 5.0, P < 0.05). Superoxide dismutase (SOD) was also higher in
      dialysis with CDA membrane that while using PS (846 +/- 171 IU/g Hb versus 522 +/
      141, P < 0.05). CONCLUSIONS: The activity of antioxidant enzymes GSHPx and SOD
      was lower with polysulfone membrane than with the cellulose acetate membrane.
      GSHPx activity also further decreased from min. 30 of dialysis with the PS
      membrane. It may be due to increased production of superoxide anion and hydrogen
      peroxide during haemodialysis with the PS. Lipid peroxidation has not been proved
      to increase during haemodialysis with the CDA or PS membrane.

PMID- 8998819
TI  - [Successful transplantation of fetal blood in a boy with leukocyte integrin
      deficiency syndrome].
AB  - The authors describe the first successful case of transplantation of
      haematopoietic stem cells in a patient with severe congenital immunodeficiency
      the syndrome of deficiency of leukocytary integrins (LAD), leukocyte adhesion
      deficiency) in the Czech Republic and, at the same time, the first successful
      transplantation of umbilical blood in this disease in the world. The six-year boy
      was completely cured by the transplantation of haematopoietic stem cells
      contained in umbilical blood sampled during delivery of his healthy brother with
      identical HLA system. The pretransplantation myeloablative preparation was
      performed by a combination of busulfan, cyclophosphamide and etoposide. The
      relatively uncomplicated posttransplantation course was secured by preventive
      administration of antibiotics and immunoglobulins. The reattachment of the stem
      cells, estimated from the peripheral blood picture, occurred 25 days after the
      transplantation, the success of the intervention was confirmed by reaching
      physiological values of originally null expression of integrins on leukocytes of
      the patient 30 days after the transplantation. The transplantation of umbilical
      blood is a very promising therapeutic method especially in children with
      leukemia, congenital severe immunodeficiencies o inborn errors of metabolism.

PMID- 8998820
TI  - [Anniversary of the National Medical Bibliography].
AB  - Bibliographia medica cechoslovaca, a comprehensive national medical bibliography,
      has played an outstanding role in providing information on Czech and Slovak
      literature since 1947. The automated system implemented in 1978 provides now
      access to this information in several ways including CD-ROM technology.

PMID- 8998821
TI  - [The revised European Code Against Malignant Tumors].
AB  - The European Code Against Cancer is a set of ten recommendations which, if
      followed, can be the best measure that an individual can take to avoid developing
      and dying from cancer. Primary and secondary prevention are considered as an
      important part of cancer control if their use is rational, based on scientific
      evidence. Six recommendations have to do with primary prevention (smoking,
      alcohol, diet, overweight, sun exposure, industrial carcinogens), two with
      secondary prevention, preferably consisting in organized screening programmes
      (uterine cervix, breast), and two with early diagnosis based on initial symptoms.
      Considering that smoking is the most important single cause of cancer in Europe
      tobacco control should be a priority. It is never too late to stop smoking:
      stopping even in middle age, prior to the onset of tobacco related illness, has a
      beneficial effect on life expectancy. If the entire population of Europe were to
      follow these guidelines a minimum of 40% reduction in cancer incidence and an
      even greater decrease in mortality could be achieved. The revised recommendations
      are the result of an agreement following 6-year experience of initially
      practising the original rules, comments and views of cancer experts throughout
      Europe; they were approved by the European Community Cancer Experts at their
      meeting in Bonn on 28-29 November 1994. Comprehension and implementation of these
      principles is of importance both for medical professionals and the general
      population of all European countries, in particular for members and candidates of
      the European Union, including the Czech Republic.

PMID- 8998822
TI  - [Importance of vitamin D in prostatic carcinoma].
AB  - BACKGROUND: Vitamin D has an antiproliferative effect on carcinomatous cells of
      the prostate. Vitamin D deficiency is considered a risk factor for the
      manifestation and development of prostate cancer. The authors present a report on
      plasma levels of vitamin D metabolites in patients with prostate cancer and
      vitamin D therapy is discussed. METHODS AND RESULTS: In 14 patients with prostate
      carcinoma plasma concentrations of the sum of hydroxylated vitamin D metabolites
      and 1.25-dihydroxy vitamin D were assessed before treatment and three months
      after treatment. For evaluation of the sum of hydroxylated metabolites the
      radiotest was used; the plasma concentration of 1.25-dihydroxyvitamin D was
      assessed by radioimmunoanalysis. For statistical evaluation Friedman's test and
      simultaneous testing were used. CONCLUSIONS: Vitamin D deficiency was not
      revealed, however, after 3 months treatment a mild vitamin D deficiency was
      manifested. In 28.5% of the patients very low levels of the sum of hydroxylated
      vitamin D metabolites and higher values of the specific prostatic antigen (PSA)
      persisted.

PMID- 8998823
TI  - [Soluble interleukin-6 receptors in the serum in multiple myeloma].
AB  - BACKGROUND: Infrequent studies, having been published so far, have brought few,
      partly contradictory, results on the importance of soluble receptor of
      Interleukin-6 (sIL-6R) in serum in patients with multiple myeloma (MM). The aim
      of the study was to find out, if there are applicable relations between the
      levels of sIL-6R and the values of selected clinical and biochemical indices and
      the levels of some cytokines in serum. METHODS AND RESULTS: The authors analyzed
      a cohort of 50 patients suffering from MM (age median 64 years, range 34-83
      years, ratio of men versus women 1.2:1.0). The soluble IL-6R and other cytokines
      were examined by ELISA assay, clinical stages of the disease were evaluated
      according to Durie-Salmon and Bataille. Increased values of sIL-6R (> 90 ng/ml)
      were in 28 (56%) of patients, median value was 87.4 (range 28.3-220 ng/l).
      Correlation analysis (Pearson test, p < 0.05) proved a statistically significant
      relation between the levels of sIL-6R and the values of beta 2-microglobulin (S
      B2M) and thymidine kinase (S-TK) in serum. There was no relation to the
      erythrocyte sedimentation velocity, haemoglobin levels, calcium, urea,
      creatinine, lactate dehydrogenase, albumin, monoclonal immunoglobulin, C-reactive
      protein, ferritin, IL-1, IL-2, sIL-2R, IL-6, TNF-alfa, and the occurrence of
      myeloma plasmocytes in bone marrow. No differences were found between the
      patients with normal values of S-B2M (< 3 ng/ml) and plasmocytes in bone marrow
      (< 5%) in comparison with the groups of patients with increased values (3-6, > 6
      ng/ml and > 20%, respectively). There was no statistically significant relation
      of the levels of sIL-6R to clinical stages of MM (1-3) and the degree of activity
      of the disease. CONCLUSIONS: Increased values of sIL-6R, detected in more than a
      half of the cohort, were, with the exception of S-B2M, S-TK and massive
      infiltration of bone marrow by myeloma plasmocytes, in no applicable relation to
      selected biochemical indices, to the level of some cytokines and to the degree of
      advancement and activity of the disease.

PMID- 8998825
TI  - [Is lithium a teratogen?].
AB  - Beginning with the seventies literature has brought a series of publications
      drawing attention to possible effects of lithium on the origin of congenital
      malformations. The discussion on the teratogenic effects of lithium in world
      literature has not come to final conclusion yet. The paper reviews some knowledge
      from home and foreign literature, dealing with the problems of lithium
      teratogenicity. A series of information has been provided on the basis of
      metaanalysis of data having been published until 1994 in the review systems
      MEDLINE, TOXLINE and Lithium Information Center database. The aim of the
      contribution has been to review the published data on this question. The
      available literature has shown that teratogenicity of lithium has not been proved
      univocally. Last studies rather suggest that lithium is not a strong teratogen.
      In view of the fact that teratogenicity of lithium cannot be safely excluded, the
      paper recommends that this kind of risk should be taken into account, if lithium
      administration is considered to be applied in pregnant women, especially during
      the first three months of pregnancy.

PMID- 8998824
TI  - [Serum levels of sialic acid in patients with type 1 diabetes mellitus in
      relation to the incidence of late complications].
AB  - BACKGROUND: Sialic acid is released from terminal oligosaccharide chain of some
      proteins of the acute phase (fibrinogen, orosomucoid, haptoglobin, etc.). Its
      serum concentrations have been commonly increased during acute inflammation. Its
      relation diabetes mellitus or late complications of the disease have been
      recently studied as well. The aim of our investigation was to determine serum
      concentrations of sialic acid in patients with diabetes mellitus Type 1 in
      relation to presence or absence of late diabetic complications. METHODS AND
      RESULTS: The authors examined a group of 62 patients treated for diabetes
      mellitus Type 1, mean age 28.7 +/- 9.8 years, having been treated for this
      disease for 11.8 +/- 8.7 years on the average. The mean level of glycated
      hemoglobin HbAlc was 9.08 +/- 1.84%. In 21 patients there were signs of diabetic
      nephropathy, seven of them already suffering from proteinuria. Retinopathy
      already developed in 12 patients. The mean concentration of sialic acid in the
      whole cohort was 1.916 +/- 0.292 mmol/litre. The correlation of serum sialic acid
      with age, duration of diabetes and glycated hemoglobin was not statistically
      significant. There was no significant difference between the serum concentration
      of sialic acid in patients without apparent nephropathy and those who were
      affected by nephropathy, or the subgroup with proteinuria (1.945 +/- 0.328
      against 1.914 +/- 0.302 mmol/litre and 1.943 +/- 0.328 mmol/litre, respectively).
      Statistically significantly higher concentrations of serum sialic acid were found
      in the subgroup of patients with present retinopathy (2.085 +/- 0.244 mmol/litre
      against 1.890 +/- 0.270 mmol/litre, P < 0.018). CONCLUSIONS: Our findings are in
      agreement with the previously proved increased concentration of proteins of the
      acute phase in diabetic patients and correspond well to the previously proved
      finding of elevated serum concentration of sialic acid in diabetic patients of
      Type 2 with retinopathy against other patients. It may not be excluded that the
      serum sialic acid could be used as a marked of the risk of late complications of
      diabetes mellitus.

PMID- 8998826
TI  - [Borrelia burgdorferi as a cause of sick sinus syndrome?].
AB  - The authors describe the case of a 42 years old man, who was implanted a
      permanent pacemaker on the basis of the sick sinus syndrome, suspected to have
      been induced by the infection with Borrelia burgdorferi. The review of world
      literature has indicated that it is an exceptional indication of permanent
      cardiac stimulation.

PMID- 8998827
TI  - [The Cochrane Collaboration. A new path to improving medical knowledge].

PMID- 8998828
TI  - [The Ceska Diakonie Hospital in Prague].

PMID- 8998829
TI  - [Pulmonary surfactant].
AB  - Study of the pulmonary surfactant system has brought important information about
      its composition, metabolism and functions in the last decades. Besides
      phospholipids an important role is played by surfactant proteins (SP-A, B, C, D).
      These proteins aid not only the reduction of the surface tension of the alveoli,
      but they are involved in regulation of surfactant synthesis, secretion and in
      local immune defense in the lungs. Impairment of surfactant was found not only in
      premature newborns (IRDS), but also in cases of meconium aspiration, pneumonia
      and in other lung diseases in adults. Therapy by stimulation of surfactant
      synthesis and secretion and by intrapulmonary application of exogenous surfactant
      was proved effective in therapy of surfactant-deficiencies.

PMID- 8998830
TI  - [Regulatory mechanisms of receptor-mediated signal transduction].
AB  - The signal activation of the target structure, mediated via receptors, could be
      also the source of some regulatory events. An intensive signaling brings about
      desensitization, sequestration and down-regulation of receptors, while in the
      case of absenting signal the sensitization and the up-regulation occur. Such
      change in the function of one receptor system could influence the function of the
      other one (we talk about cross-regulation). This review is focused on mechanisms
      of the homologous regulation (changes in the pathway activated by the appropriate
      type of receptor) and possible mechanisms of cross-regulation (changes in pathway
      activated by other type of receptor).

PMID- 8998831
TI  - [Nuclear magnetic resonance and aspects of its use in diagnosis and research on
      metabolic disorders of skeletal muscles].
AB  - Introduction of nuclear magnetic resonance has enabled direct measurements of
      muscle metabolism in vitro and in vivo. In the presented paper some theoretical
      and practical applications mainly 31P NMR spectroscopy in research and
      diagnostics of muscle skeletal diseases are given. In spite of some limitations,
      the most important advantage of NMR technique is its non-destructive character,
      the possibility of simultaneous observation of several phosphorylated metabolites
      in a muscle tissue and the simple method of sample preparation. 31P NMR is a
      useful tool for studying and detection of muscle diseases and at the same time
      for its safety for patients.

PMID- 8998832
TI  - [Computer simulation of the activity of selected functional systems in the body
      during maintenance of homeostasis].
AB  - A computer with an appropriate software may greatly contribute to the
      understanding of relationships and interactions among physiological processes in
      the body and thus to influence the speed and effectiveness of learning. Presented
      computer model "The Internal Environment", briefly described in this paper,
      illustrates this fact. This model allows to simulate behavior of some functional
      systems in various experimental situations. The subsequent evaluation of the
      activity changes in these systems can help students to understand and interpret
      principles of the activity of the homeostatic mechanisms. That is why the
      computer simulation is an appropriate starting point at seminars where problems
      of the internal environment stability maintenance are to be discussed.

PMID- 8998833
TI  - [The Czechoslovak Physiology journal and undergraduate and postgraduate
      education].

PMID- 8998834
TI  - [The teaching of physiology at Charles University in Prague].

PMID- 8998835
TI  - Michael-type addition of illudin S, a toxic substance from Lampteromyces
      japonicus, with cysteine and cysteine-containing peptides in vitro.
AB  - Reactions of illudin S with cysteine derivatives (cysteine methyl ester,
      glutathione and a peptide, Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg) were
      investigated. In the reaction with cysteine methyl ester, four products (P1, P2,
      P3, P4) were obtained and their structures were determined, on the basis of MS
      and NMR data, to be adducts of the mercapto group of cysteine methyl ester with
      the alpha,beta-unsaturated carbonyl group of illudin S. In the reactions with
      glutathione and the peptide, two addition products in each case were identified
      by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and NMR analyses.
      The structures of these adducts also indicated that the alpha,beta-unsaturated
      carbonyl group in illudin S behaves as a Michael acceptor for the mercapto group
      in cysteine.

PMID- 8998836
TI  - Isolation of three new azaphilones, luteusins C, D, and E, from an ascomycete,
      talaromyces luteus.
AB  - Three new azaphilones, named luteusins C, D, and E, were isolated from an
      Ascomycete, Talaromyces luteus, together with luteusins A and B (previous
      tentative designations: TL-1 and -2, respectively), which had formerly been
      isolated as monoamine oxidase (MAO)-inhibitory azaphilones from the fungus. The
      new compounds had no MAO-inhibitory activity.

PMID- 8998837
TI  - Synthesis and pharmacological evaluation of N-(6-functionalized-amino-3-pyridyl)
      N'-bicycloalkyl-N''-cyanoguanidine s as antihypertensive agents.
AB  - A series of amino acid conjugates of N-(6-amino-3-pyridyl)-N'-[exo
      bicyclo[2.2.1]hept-2-yl]-N''- cyanoguanidine (4) were prepared and evaluated as
      antihypertensive agents. The parent compound 4 showed potent potassium channel
      opening and antihypertensive activities, but with undesirable changes of the
      urinary balance of electrolytes. However, alanine and histidine congeners (9,19)
      reduced this undesirable side effect of 4 through improved pharmacokinetics
      without loss of antihypertensive activity. They also provided additional
      information on the structural requirements for pinacidil-type potassium channel
      openers.

PMID- 8998838
TI  - Optically active antifungal azoles. VI. Synthesis and antifungal activity of N
      [(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazo l-1-
      yl)propyl]-N'-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones and 5(1H,4H)
      tetrazolones.
AB  - A new series of optically active antifungal azoles, N-[(1R,2R)-2-(2,4
      difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-tria zol-1- yl)propyl]-N'-(4
      substituted phenyl)-3(2H,4H)-1,2,4-triazolones (1,2) and 5(1H,4H)-tetrazolones
      (3), were prepared from the triflate derivative of (1S)-1-[(2R)-2-(2,4
      difluorophenyl)-2-oxiranyl]ethanol (13) by an SN2 displacement reaction with the
      anion of an azolone (17-19) and subsequent ring-opening reaction with 1H-1,2,4
      triazole. The optically active oxiranylethanol 13 was synthesized from methyl (R)
      lactate in a stereo-controlled manner. The azolones 1-3 prepared showed potent
      antifungal activities in vitro and in vivo.

PMID- 8998839
TI  - Partially-hydrophobized polymer particles derived from N,N
      dimethylaminopropylacrylamide for endotoxin removal from acidic protein solution.
AB  - Novel copolymeric adsorbents for the selective removal of endotoxin from an
      acidic protein solution were prepared. The adsorbents comprise spherical
      copolymers derived from N,N-dimethylaminopropylacrylamide (DMAPAA) and
      divinylbenzene (DVB). When the molar ratio of DMAPAA to DVB was 80/20 (amino
      group content: 5.1 meq/g) and the pore size (molecular mass exclusion of
      polysaccharide, Mlim) was 4000 to 10000, DMAPAA/DVB showed high endotoxin
      adsorbing activity at pH 5.0 to 9.0 and ionic strengths of mu = 0.05 to 0.4. The
      capacity of the adsorbent (Mlim: 4000) was 390 micrograms of endotoxin
      (lipopolysaccharide purified from E. coli O111:B4) per ml of the adsorbent using
      the batchwise method. The apparent dissociation constant between endotoxin and
      the adsorbent was 2.2 x 10(-12) M. On the other hand, the adsorption of bovine
      serum albumin, an acidic protein, by the adsorbent increased with an increase in
      Mlim from 4000 to 10000, but decreased with an increase in ionic strength (mu)
      from 0.05 to 0.2. As a result, DMAPAA/DVB (80/20) (Mlim: 4000) selectively
      removed endotoxin from various acidic protein solutions at pH 7.0 and mu = 0.05.
      The residual concentration of endotoxin in the protein solution always decreased
      to a concentration lower than 0.1 ng/ml, and recovery of the protein was more
      than 97%.

PMID- 8998840
TI  - Pharmacologically active components of a Peruvian medicinal plant, huanarpo
      (Jatropha cilliata).
AB  - From Jatropha cilliata M. Arg., a Peruvian medicinal plant, isoorientin and
      orientin were isolated as anxiolytic components by using the isolation guide of
      anti-conflict effect in mice. Several related flavonoids were also tested for
      this effect. Another bioassay-guided isolation using the acetic acid-induced
      writhing method gave a coumarin compound, fraxetin, as an analgesic principle.

PMID- 8998842
TI  - Studies on internal structure of tablets. VI. stress dispersion in tablets by
      excipients.
AB  - The aim of this study was to reduce the stress concentration of a medicine by
      dispersing the stress in tablets at tableting by addition of excipients. The
      mechanism of the stress dispersion was elucidated. Phenacetin (PHE) was used as a
      model of crystalline medicine with a high brittleness, and the degree of stress
      dispersion was evaluated by the change in the exposed surface area of PHE. To
      learn the mechanical strength of tablets, the crushing strength and friability
      were measured, their internal structure was analyzed by the porosity and pore
      size distribution, and stress relaxation experiments were performed. The results
      were as follows. Calcium silicate (Florite RE, FLR) showed a high stress
      dispersion effect, adding a high formability and mechanical strength to tablets.
      It was thought that the high stress dispersion resulted from the rapid stress
      relaxation caused by the plastic deformation and brittleness fracture of pores in
      FLR under a low compression pressure. Thus the stress caused locally on PHE
      particles may disperse.

PMID- 8998841
TI  - Endothelin receptor antagonist triterpenoid, myriceric acid A, isolated from
      Myrica cerifera, and structure activity relationships of its derivatives.
AB  - As the first non-peptide endothelin receptor antagonist from a higher plant, a
      new triterpenoid, myriceric acid A (50-235) (1) was isolated from the bayberry,
      Myrica cerifera. Myriceric acid A (1) inhibited not only an endothelin-1-induced
      increase in cytosolic free Ca2+ concentration (IC50 = 11 +/- 2 nM) but
      [125I]endothelin-1 binding in rat aortic smooth muscle cells (Ki = 66 +/- 15 nM).
      Two new related triterpenoids, myriceric acid C (6), and myriceric acid D (8),
      were also isolated. Furthermore, the chemical modification of these natural
      products led to the synthesis of sulfated derivatives (13, 14, 15) which showed
      1.5 to 20 times higher affinity for endothelin receptors. The structure activity
      relationships of myriceric acids and their derivatives are discussed.

PMID- 8998843
TI  - l-Menthol, oleic acid and lauricidin in absorption enhancement of free and sodium
      salt of diclofenac using ethanol treated silicone membrane as model for skin.
AB  - The mechanism of l-menthol, oleic acid and lauricidin as enhancers on
      percutaneous absorption was examined using diclofenac (DH) as a hydrophobic drug
      and sodium diclofenac (DNa) as a hydrophilic drug in in vitro diffusion
      experiments with two kinds of membranes: ethanol-treated and untreated silicone
      membranes; these were models for the lipid and pore pathways of skin. A 20% w/w
      ethanol-aqueous solution decreased the flux of DH but increased the flux of DNa
      significantly across the treated membrane compared with those fluxes across the
      untreated membrane, suggesting that DH penetrated by the lipid pathway and DNa by
      the pore pathway. The permeability of DNa through the pore pathway decreased
      significantly across the treated membrane with the addition of oleic acid and
      lauricidin. l-Menthol increased the permeability coefficients of DH and DNa more
      in a treated membrane than in an untreated one, showing the same tendency as in
      rat skin. Thus, while oleic acid and lauricidin did not increase the permeation
      of DNa by the pore pathway, l-menthol appeared to enhance the permeation of the
      drug by both the lipid and pore pathways.

PMID- 8998844
TI  - Relationship between the 13C-NMR chemical shift and the carcinogenic activity of
      benz[a]anthracenes.
AB  - A thorough NMR spectroscopic investigation was made on 7,12
      dimethylbenz[a]anthracene (1) and the 1H- and 13C-NMR spectra were completely
      assigned. We compared the 13C-NMR chemical shifts (delta) of three
      benz[a]anthracenes, including compound 1, whose carcinogenicities vary largely,
      and investigated the relationship of the delta and carcinogenicity. It was found
      that the delta values at the C1, C2, and C6 positions differed significantly
      between the carcinogenic and noncarcinogenic compounds.

PMID- 8998845
TI  - An alternative access to a trisaccharide repeating unit of the capsular
      polysaccharide of Streptococcus pneumoniae serotype 19A.
AB  - A chemical synthesis has been achieved for beta-D-ManNAc-(1-->4)-alpha-D-Glc-(1-
      >3)-L-Rha, a trisaccharide repeating unit of the capsular polysaccharide of
      Streptococcus pneumoniae serotype 19A, by stepwise link-up of the suitably
      functionalized, constituent sugar units. A beta-selective glycosylation of
      trimethylsilylethyl glucoside having free 4-OH with 2-(benzoyloxyimino)-2
      deoxyglycosyl bromide, followed by manno-selective hydroboration, N-acetylation,
      and functionalization of the anomeric center (1-OSE-->1-OH-->1-F), gave a key
      disaccharide donor, beta-D-ManNAc-(1-->4)-alpha-D-Glc-(1-->F. Ensuing
      glycosylation of an L-rhamnosyl acceptor with the donor substrate afforded, after
      deblocking, the target trisaccharide in 6.5% yield over 13 steps from D-glucose.

PMID- 8998846
TI  - Isolation of cholesteryl ester transfer protein inhibitors from Panax ginseng
      roots.
AB  - We have isolated cholesteryl ester transfer protein (CETP) inhibitors from the
      extract of Korean Panax ginseng C. A. Meyer roots and identified them as
      polyacetylene analogs. These compounds inhibit human CETP with IC50 values of
      around 20-35 mg/ml.

PMID- 8998847
TI  - Novel phorbol analogs which bind to protein kinase C (PKC) without activation.
AB  - 13-Deacetoxy-11-demethyl-phorbol derivatives with acyl groups of various lengths
      (from hexanoyl to tetradecanoyl) at the C-12 position were synthesized in an
      optically active form. Although considerable binding affinities to PKC were
      observed by analogs 3-7, no activation of PKC was seen even at 10 microM.

PMID- 8998848
TI  - New hypoglycemic constituents in "gymnemic acid" from Gymnema sylvestre.
AB  - Investigation of hypoglycemic activity of major saponin constituents from
      "gymnemic acid", a crude saponin fraction of G. sylvestre, exposed not only two
      new saponins, gymnemosides a (1) and b (2), but also gymnemoside b and gymnemic
      acid V (7) as active principles. Furthermore, an acetyl group linked 16- or 22
      hydroxy group in 1 and 2 was found to migrate easily to primary 28-hydroxyl
      group, while acyl migration from 28-hydroxy group in 3 was little observed.

PMID- 8998849
TI  - Rosenthal fiber encephalopathy presenting with demyelination and Rosenthal fibers
      in a solvent abuser: adult Alexander's disease?
AB  - We report a neuropathological case of the brain of a 22-year-old male solvent
      abuser. He had also been diagnosed as suffering from schizophrenia.
      Neurohistology revealed the presence of Rosenthal fibers (RFs) in subpial and
      perivascular collections in the medulla, the floor of the 3rd and 4th ventricles,
      and also in the spinal cord. There was mild demyelination in the frontal,
      temporal, and parietal lobes, as well as the left dorsal column in the spinal
      cord. There was bilateral basal ganglia calcification. Demyelination and RFs have
      been the hallmark of the diagnosis of adult Alexander's disease. We urge that
      these are insufficient criteria for this nosological category, and suggest the
      alternative and more appropriate label of Rosenthal fiber encephalopathy. In view
      of the known toxic, clinical effects of chronic solvent abuse, and the lack of
      knowledge of the neuropathological effects, we also tentatively note the
      association of the solvent abuse with the neuropathology, but are unable to
      assert any causal link.

PMID- 8998851
TI  - Fibromuscular dysplasia of the internal carotid artery: a clinicopathological
      study.
AB  - Although angiographic changes of fibromuscular dysplasia (FMD) of the carotid
      artery are regularly noted, histologic confirmation is rare. We therefore
      reviewed all patients with a histologic diagnosis of FMD affecting the internal
      carotid artery who were seen at our institution over a 25-year-period. FMD of the
      internal carotid artery was a very rare autopsy finding and was detected in only
      4 of 20,244 consecutive autopsies (0.02%). In an additional 6 patients FMD of the
      internal carotid artery was identified in a surgical specimen. All patients were
      female and their mean age was 53 years. Nine patients had the medial form of FMD
      and 1 the intimal form. By immunohistochemistry the lesions consist of
      proliferations of smooth muscle with a minor fibroblastic component. FMD was
      rarely limited to 1 carotid artery and multivessel involvement was present in 9
      patients. In reference to this experience epidemiologic, pathologic, and
      etiologic features of FMD of the carotid arteries are discussed.

PMID- 8998850
TI  - Intramyelinic edema in chronic inflammatory demyelinating polyneuropathy.
AB  - We describe a patient affected by chronic inflammatory demyelinating
      polyneuropathy (CIDP) whose sural nerve biopsy revealed a marked edema of the
      myelin sheath. Since this change has been previously described in human
      peripheral nerves only in CIDP patients, we suggest that intramyelinic edema may
      have a role in the pathogenesis of demyelinating neuropathies.

PMID- 8998852
TI  - An immunohistochemical study of neurofibrillary tangle formation in post
      encephalitic Parkinsonism.
AB  - Neurofibrillary tangle (NFT) formation is a feature of postencephalitic
      Parkinsonism (PEP) and Alzheimer's disease (AD). Tangle formation has been
      compared immunohistochemically in these 2 conditions. Staining patterns for tau
      protein, ubiquitin and beta/A4 amyloid protein were studied in frontal lobe,
      hippocampus, and midbrain in 2 classical cases of PEP, 2 cases of AD and 2
      controls matched for age and sex. NFTs were present in all cases, but with
      varying frequency: all tangles were tau-positive and many were ubiquitinated. In
      the frontal cortex and hippocampus, irrespective of the case category, tangle
      formation was associated with beta/A4 amyloid deposition. A similar association
      was present in the 2 AD cases in the midbrain. However, in PEP tangle formation
      in the midbrain was not associated with adjacent beta/A4 amyloid deposition. This
      finding raises the possibility that the pathogenetic mechanism of tangle
      formation in PEP is different from that of AD, although the final cellular
      morphological expression of abnormality in both conditions is similar.

PMID- 8998853
TI  - Creutzfeldt-Jakob disease in an Iranian: the first clinico-pathologically
      described case.
AB  - This is the first report of a definite case of Creutzfeldt-Jakob disease in an
      Iranian and it has been confirmed by a neuropathological study and by the
      immunoelectrophoretic demonstration of PrP, the pathological amyloid protein
      specific to the spongiform encephalopathies. The clinical course and the
      topography and severity of brain pathology classify this case as of
      panencephalopathic type and support the view of different phenotypic expressions
      of CJD in relation to the existence of multiple strains of the causative agent.

PMID- 8998854
TI  - Microglial nodule encephalitis: limited CNS infection despite disseminated
      systemic cryptococcosis.
AB  - A 28-year-old patient with AIDS was found at autopsy to have disseminated
      cryptococcal infection involving the lungs, spleen, lymph nodes, kidneys,
      gastrointestinal tract, thyroid, bone marrow, and liver. Despite widespread organ
      dissemination the patient did not have clinical or pathological evidence of
      meningitis. Microscopic examination of the brain showed cryptococci limited to
      the brainstem and basal ganglia; microglial nodules with multinucleate giant
      cells, a histological hallmark of HIV-1 encephalitis, were shown to contain
      Cryptococcus neoformans. This feature may suggest a form of synergism between HIV
      1 and Cryptococcus neoformans. This case demonstrates an unusual form of
      cryptococcal neurotropism with limited CNS involvement.

PMID- 8998855
TI  - Mitochondrial changes in muscle phosphoglycerate kinase deficiency.
AB  - X-linked phosphoglycerate kinase (PGK) deficiency is a rare disorder which
      affects the glycolytic pathway and leads to reduced ATP production. Clinically,
      PGK deficiency is often associated with nonspherocytic hemolytic anemia and
      symptoms caused by disturbances of the central nervous system. In addition,
      myopathy characterized by weakness, cramps, intolerance to exercise, and
      myoglobinuria has been described in a few cases. We here report on a 23-year-old
      man who presented with episodes of muscular weakness, cramps, rhabdomyolysis, and
      renal failure induced by intensive physical exercise. Biochemical analysis of
      muscle specimens disclosed markedly reduced PGK activity (11.5% compared to
      normal controls). A moderate increase of glycogen was seen in numerous muscle
      fibers. Mitochondria in muscle fibers and endothelial cells showed accumulations
      of glycogen. In muscle fibers unusually large matrix granules were present in
      several mitochondria. A sural nerve biopsy disclosed scattered large
      hypomyelinated axons without evidence of demyelination and remyelination. These
      findings indicate involvement of mitochondria in this case of symptomatic PGK
      deficiency.

PMID- 8998856
TI  - Sporadic amyotrophic lateral sclerosis with dementia and Cu/Zn superoxide
      dismutase-positive Lewy body-like inclusions.
AB  - This report concerns a case of sporadic amyotrophic lateral sclerosis (ALS) with
      dementia and Lewy body-like hyaline inclusions (LBHIs). The patient was a 70-year
      old woman who initially showed memory disturbance and later developed bulbar
      palsy, muscle atrophy and weakness. The total clinical course was 51 months. The
      postmortem examination revealed superficial sponginess and subcortical gliosis in
      the frontotemporal cortices. Ubiquitin-positive intraneuronal inclusions were
      found in small cortical neurons of the frontotemporal lobe. Neuronal loss was
      marked in the spinal anterior horn with degeneration of the pyramidal tracts. The
      anterior horn cells had ubiquitin-immunoreactive skein-like inclusions and Bunina
      bodies. LBHIs were present in the lumbar horn; ultrastructurally they were
      composed of randomly arranged thick filamentous structures studded with granules.
      The LBHIs were intensely stained with anti-ubiquitin antibody. As in familial ALS
      and in certain cases of sporadic ALS, some of these inclusions reacted with an
      antibody against Cu/Zn superoxide dismutase, the enzyme whose gene was recently
      found to be mutated in some forms of familial ALS.

PMID- 8998858
TI  - Amyloid deposits of immunohistochemically different classes in the ligamentum
      flavum in biopsies from patients with herniated discs or lumbar spinal stenosis.
AB  - Ligamenta flava of 100 patients (n = 107 tissue blocks) were examined for the
      presence of amyloid by means of polarization microscopy after staining with Congo
      red. Ninety-three ligamenta flava were resected due to operation of herniated
      discs while 14 ligamenta flava were obtained after surgical treatment of lumbar
      spinal stenosis. Amyloid of various amounts (score I-III) and 4 morphologically
      different appearances were detected in the ligamenta flava of 12 patients. In 6
      patients small amyloid deposits were seen along elastic fibres (pattern 1) and/or
      minute, comma-like deposits in certain areas (pattern 2). In 5 other patients
      amyloid deposits in form of large lumps were present (pattern 3) intermingled
      with deposits of pattern 1 and/or 2. Only 1 patient could be detected with
      amyloid deposits partly associated with blood vessels (pattern 4). The amyloid
      containing tissue samples (n = 13) were immunohistochemically analyzed using anti
      AA-, anti-A lambda-, anti-A kappa-, anti-ATTR- and anti-A beta 2m-antibodies
      which are able to identify the major known amyloid classes of tissue sections.
      Tissues with pattern 1 and 2 amyloid deposits did not react above background with
      any of the antibodies. In contrast, the 5 patients with pattern 3 amyloid stained
      strongly with anti-ATTR but not with the other antisera. In this group,
      therefore, senile systemic amyloid (sporadic ATTR) was also identified which had
      not been detected at this site before. Consistent with this finding is the
      advanced age of these patients which was seen to be significantly higher than the
      average age of the entire group of patients examined.

PMID- 8998857
TI  - Dysembryoplastic neuroepithelial tumor: a clinicopathologic and
      immunohistochemical study of 11 tumors including MIB1 immunoreactivity.
AB  - The dysembryoplastic neuroepithelial tumor (DNT) is a rare, recently recognized
      neoplasm, characterized by a mixed glial-neuronal cell proliferation. We studied
      11 cases of DNT including 6 males and 5 females (age range 2.1-39.4 years, mean
      13.8 years). All patients presented with chronic epilepsy of 4.8 years mean
      duration. Nine tumors were located in the temporal lobe and 2 in the frontal
      lobe. Four tumors were located on the right side and 7 on the left. All tumors
      were characterized by a predominant oligodendrocyte-like cell component with
      intermixed normal appearing neurons and astrocytes. All were focally microcystic
      and 7 of 9 evaluable tumors were multinodular. Other observed histologic features
      included a focal arcuate vascular pattern in 7 tumors, calcification in 4 tumors,
      and a rare mitotic figure in 2 tumors. Necrosis and vascular hyperplasia were not
      observed in any of the tumors. Cortical architectural disorganization (cortical
      dysplasia) was observed in 9 of 10 evaluable cases. MIB1 (a marker of cellular
      proliferation) immunostaining was performed in all 11 tumors and MIB1 indices
      (number of positive tumor cells/100 tumor cells counted) ranged from 0-0.6 (mean
      0.2). Four patients required at least 1 additional surgical procedure for tumor
      recurrence, related to an incomplete initial excision 2.1-4.4 years after their
      initial operation. All patients are seizure-free at their last follow-up. DNTs
      are low grade neoplasms which typically present with chronic epilepsy, are most
      frequently located in the temporal lobe, and occur most frequently in pediatric
      patients. Their appearance and association with cortical dysplasia suggest a
      maldevelopmental origin. The generally slow growth and relatively benign nature
      of DNT is reflected by their low MIB1 index.

PMID- 8998859
TI  - Symptomatic osteolipoma of the tuber cinereum.
AB  - Intracranial osteolipomas are rare lesions which occur in the region of the tuber
      cinereum. All cases reported to date have been incidental autopsy findings. We
      describe a patient who presented with a variety of neurological symptoms and had
      a typical osteolipoma surgically removed.

PMID- 8998860
TI  - Dorsal root gangliopathia presenting with rapidly progressing sensory
      polyneuropathy.
AB  - A 52-year-old woman developed progressive sensory polyneuropathy leading to death
      in 1.5 years. Electromyography and peripheral nerve biopsy had revealed severe
      axonal degeneration. Neuropathological examination showed involvement of all
      dorsal root ganglia with loss of the bipolar nerve cells, degeneration of the
      remaining nerve cells, Nageotte's residual nodules, and scattered lymphocytes.
      The posterior columns of the spinal cord and the sensory spinal roots revealed
      secondary loss and degeneration of the nerve fibers. The etiology is unknown but
      an autoimmune-mediated reaction effecting the nervous system is strongly
      suggested.

PMID- 8998861
TI  - The knee as a biologic transmission with an envelope of function: a theory.
AB  - The knee can be characterized as a complex set of asymmetrical moving parts
      acting together as a living biologic transmission. The purpose of this system is
      to accept, transfer, and dissipate loads generated at the ends of the long
      mechanical lever arms of the femur and tibia. In this analogy, the various
      ligaments represent sensate adaptive linkages, the articular cartilages represent
      bearings, and the menisci, mobile sensate bearings within the transmission. The
      muscles represent both living engines providing motive forces, and brakes and
      dampening systems under complex neurologic control mechanisms. The range of load
      that can be applied across an individual joint in a given period without
      supraphysiologic overload or structural failure can be termed the envelope of
      function. This range of homeostatic loading can be graphed with increasing
      applied loads on the vertical axis and the frequency of loading on the horizontal
      axis. At least 4 categories of factors together determine the envelope of
      function for a given joint including anatomic, kinematic, physiologic, and
      treatment factors. This theory of joint function can result in a more rational
      clinical approach to treating patients with knee injuries and other orthopaedic
      conditions. Orthopaedic therapy should be designed to maximize the envelope of
      function of musculoskeletal systems with the least degree of risk.

PMID- 8998862
TI  - Revision anterior cruciate ligament surgery: experience from Pittsburgh.
AB  - Twenty-five patients who underwent revision anterior cruciate ligament
      reconstruction after failure of a previous intraarticular reconstruction were
      retrospectively reviewed. Before revision, all patients reported functional
      instability with sports or activities of daily living and exhibited increased
      anterior patholaxity on physical examination. Fresh frozen irradiated allograft
      tissue was used for all revisions. A comprehensive knee analysis using a
      subjective and objective system was done for all patients preoperatively and at
      the time of final followup. The mean age at revision surgery was 25 years and
      average time from primary to revision surgery was 30 months. Average length of
      followup was 28 months. The anteroposterior displacement was improved in all
      patients. Sixty-four percent of patients had less than 5 mm side to side
      difference on arthrometric testing. Eighty percent had either a Grade 0 or Grade
      1 pivot shift. The average modified Cincinnati Knee Score was 68 with the results
      of 88% of patients rated abnormal by International Knee Documentation Committee
      guidelines. Seventy-six percent of patients were satisfied with their results and
      would elect to have revision surgery again. These results show that patients
      having revision anterior cruciate ligament reconstruction for a failed
      intraarticular reconstruction had improvement in their functional status compared
      with prerevision; however, they did not achieve the same level of satisfactory
      results as primary anterior cruciate ligament reconstruction.

PMID- 8998863
TI  - Revision anterior cruciate ligament surgery: experience from Germany.
AB  - From 1976 to 1992, reconstruction after failed anterior cruciate ligament repair
      or reconstruction was done for 87 patients (8%) compared with 1064 primary
      operations at the authors' institution. Fifty-seven patients had 1 previous
      reconstruction, 27 patients had 2, and 3 patients had 3 or more previous
      reconstructions. Fifty-two patients (60%) were satisfied with their results after
      a mean followup time of 8 years (range, 2-18 years). Lysholm scores after
      revisions (68 +/- 12) were significantly inferior compared with scores after
      primary anterior cruciate ligament surgery (83 +/- 14). The authors favor the use
      of the patellar tendon or quadriceps tendon autograft in revision surgery. Medial
      meniscus reconstruction is done whenever possible, or the medial meniscus is
      replaced by autograft tissue. Open or arthroscopic techniques are used, depending
      on the individual case.

PMID- 8998864
TI  - Revision anterior cruciate ligament surgery: experience from Cincinnati.
AB  - Prospective studies were done to determine the outcome of allografts and
      autografts used for revision anterior cruciate ligament reconstruction. The
      allograft group was comprised of 65 patients observed for a mean of 42 months
      postoperatively; the autograft (bone-patellar ligament-bone) group contained 20
      patients observed for a mean of 27 months postoperatively. KT-2000 testing and a
      comprehensive knee examination were done on all the patients. The Cincinnati Knee
      Rating System was used for assessment. Significant improvements were noted in all
      patients for symptoms, functional limitations, anteroposterior displacements,
      pivot shift tests, and overall rating scores. KT-2000 results showed 53% of the
      allograft group and 67% of the autograft group had less than 3 mm increased
      displacement (not statistically significant). The overall failure rates were 33%
      for the allografts and 27% for the autografts. Preoperative planning and
      technical aspects of anterior cruciate ligament revision procedures are
      described. The authors prefer bone-patellar ligament-bone autografts for anterior
      cruciate ligament revision, although the data presented were considered
      preliminary. Bone-patellar ligament-bone allografts may be used when autogenous
      tissues are not available, because they offer reasonable success rates for
      patients who are symptomatic with daily activities.

PMID- 8998865
TI  - The future of anterior cruciate ligament restoration.
AB  - Advancements in the understanding of anatomy, kinematics, and physiology should
      improve future treatment of anterior cruciate ligament injured knees. The
      ultimate goal of full restoration of an anterior cruciate ligament injured knee
      to preinjury status, may be possible in the distant future through genetic
      manipulation inducing regeneration of tissues. In the midterm future, resorbable
      stents with incorporated bioactive growth factors have the potential of inducing
      normal anterior cruciate ligament anatomy without the need for detrimental
      harvesting of the patient's tissues, or risk of microbial transmission with the
      use of an allograft. In the near future, the development of more benign
      autografts and allografts is possible along with methods of resorbable fixation
      of the graft to bone. Future development of 3-dimensional arthroscopic
      visualization and robotic surgical techniques have the potential for improvement
      in graft placement. Advancements in treatment of anterior cruciate ligament
      deficient knees also can be expected from nonsurgical areas, such as control of
      muscle atrophy, enhancing cerebellar-proprioceptive rehabilitation, and better
      bracing techniques. The basic principle of therapy should be to maximize the
      functional load acceptance and transference capacity of the knee with the least
      degree of risk to the patient.

PMID- 8998866
TI  - A modified darrach procedure for treatment of the painful distal radioulnar
      joint.
AB  - Controversy exists regarding the best treatment for pain and instability of the
      distal radioulnar joint. Until recently, the Darrach distal ulnar resection had
      been the standard procedure for this disorder. The Bowers hemiresection
      interposition arthroplasty, however, and the Watson matched distal ulna resection
      have been developed to preserve the styloid attachment of the triangular
      fibrocartilage complex. This article presents a retrospective chart review of a
      consecutive series of patients who had painful distal radioulnar joints which
      were treated with a modified Darrach procedure. This procedure was performed to
      alleviate the problems of impingement and styloid carpal abutment during grip,
      and provide stabilization. Fifteen patients (16 wrists) were seen during followup
      for an average of 37 months after resection arthroplasty of the distal ulna was
      performed; 6 procedures were revisions. The results were uniformly good with
      marked alleviation of pain in all but 1 patient. Patients experienced consistent
      improvement toward pain-free pronation/supination and increased grip strength.

PMID- 8998868
TI  - Uncemented revision total hip arthroplasty: a 4-to-6-year review.
AB  - A review of 52 cementless revision total hip arthroplasties in 51 patients with a
      4- to 6-year clinical and radiographic followup was conducted. Mallory Head
      titanium alloy prostheses using proximally porous-coated femoral stems were used
      in all cases. There were 2 revisions of the femoral component only and 1 was an
      acetabular revision. At an average followup of 4.6 years, 5 (10%) unstable
      femoral stems had been rerevised and another 7 (14%) stems were unstable
      radiographically, but rerevision had been refused or postponed. Three (6%)
      sockets were considered unstable but no acetabular revisions have been done.
      Eleven of the 12 stem failures were in femora with moderate or severe prerevision
      femoral bone loss. The Harris Hip Score averaged 76 points for the entire group,
      and scores were much worse in patients with preexisting femoral bone deficiency.
      Twenty (40%) femoral fractures occurred during stem insertion. This short-term
      study shows inadequate fixation of proximally porous-coated femoral stems in
      revisions with femoral bone loss; adequate stability is achieved if bone loss is
      limited. Porous-coated acetabular fixation using fins and screws where necessary
      is adequate in the majority of cases.

PMID- 8998867
TI  - Patient selection for lumbar discectomy with a revised objective rating system.
AB  - Inappropriate patient selection for the surgical treatment of lumbar disc
      herniation remains a major cause of failed laminectomy syndrome. Further
      experience with the use of a revised objective rating system for patient
      selection for lumbar laminectomy and discectomy for the treatment for disc
      herniation is presented. Based on the severity of findings within each of 4
      categories (neurologic signs, root tension signs, imaging findings, and
      psychosocial environment), numeric scores are derived. A maximum of 25 points is
      available in each category, for a total of 100 points. Scores were determined
      prospectively in 275 patients who were treated by laminectomy for lumbar disc
      herniation. Followup averaged 4 years (range, 1 to 12.8 years). Overall, there
      were 226 (82%) good results, 26 (10%) fair results, and 23 (8%) poor results.
      Among the 89 patients with compensation/litigation issues, 52 (58%) had good
      outcomes; 16 (18%), fair outcomes; and 21 (24%), poor outcomes. Of the 186
      patients without compensation or litigation issues, 174 (94%) had good results;
      10 (5%), fair results; and 2 (1%), poor results. The objective rating score was
      highly predictive of patient outcome at followup.

PMID- 8998869
TI  - Synovial cyst formation complicating total hip arthroplasty: a case report.
AB  - The most frequent causes of unilateral limb swelling unrelated to trauma or
      surgery are deep venous thrombosis, chronic venous insufficiency, and primary
      lymphedema. Other important but less frequent causes include infection and
      neoplasm. Neoplasms may cause limb swelling, either by soft tissue enlargement or
      incidental compression of venous or lymphatic structures. Reported here is an
      unusual case of a patient with unilateral leg swelling and an inguinal mass
      presenting years after total hip arthroplasty. The unilateral leg swelling was
      caused by compression of the right common femoral vein by a synovial cyst arising
      from the hip joint. Although only 2 cases have been described in the literature,
      such cyst formation is not uncommon with loose acetabular components. The most
      apparent cause of cyst formation was polyethylene debris. Treatment efforts
      should be directed at the source of the debris intraarticularly.

PMID- 8998870
TI  - Revascularization in nontraumatic osteonecrosis of the femoral head.
AB  - To study the revascularization pattern of nontraumatic osteonecrosis,
      superselective angiography of the femoral medical circumflex artery was done
      twice on 13 hips for which no treatment had been given. Angiographic evaluation
      of the hips with early-stage osteonecrosis not visible on radiographs showed the
      absence of superior retinacular arteries from the stump in all hips. Penetration
      of small vessels was seen on 6 hips. Bony scintigraphy of 13 hips and magnetic
      resonance imaging of 9 hips were taken at about the same time. Bony scintigraphy
      and magnetic resonance imaging results were positive in 11 of 13 hips and in all
      9 hips, respectively. The patients were observed until evidence of necrosis
      appeared on radiographs. When this sign became evident, a second angiography was
      conducted, which indicated the penetration of erratically formed vessels with
      increase in size in 12 hips. It was assumed that the blood supply from the
      superior retinacular arteries was interfered with in large areas of the femoral
      head and that revascularization started with the formation of small vessels,
      followed by further penetration of large vessels.

PMID- 8998872
TI  - Quantitative scintigraphic evaluation of total knee arthroplasties: a feasibility
      study.
AB  - For the development and validation of a quantitative approach to the analysis of
      bone scans after total knee arthroplasty, 39 consecutive patients with 40
      prostheses (6 males, 33 females; mean age, 70 years) were scheduled for clinical,
      radiographic, and scintigraphic examination ranging from 9 to 90 months after
      surgery. Twenty-seven total knee arthroplasties were considered to be
      asymptomatic and 13 symptomatic according to the clinical and radiographic
      findings. Significant differences were found for 99mTc-methylene diphosphonate
      uptake for femur and tibia and between symptomatic and asymptomatic patients. A
      reference range was determined for radionuclide uptake in the periprosthetic bone
      of the 27 asymptomatic total knee arthroplasties; this range was then used to
      identify loose total knee arthroplasties among the 13 symptomatic knees. With a
      clinical and radiographic followup performed 1 year after scintigraphy as a
      standard of comparison, a sensitivity of 88% (7/8) and a specificity of 100%
      (5/5) was demonstrated. These preliminary results suggest the feasibility of a
      quantitative approach to the scintigraphic evaluation of total knee
      arthroplasties after the first postsurgical year.

PMID- 8998871
TI  - Neuropathy secondary to pigmented villonodular synovitis of the hip.
AB  - Pigmented villonodular synovitis is a benign proliferative process of unknown
      origin that may cause extensive bone and joint destruction. Patients with this
      condition typically present with symptoms of mild discomfort and associated
      stiffness of the involved joint; however, the spectrum of presentations is broad.
      Although pigmented villonodular synovitis begins in, and usually is confined
      within, a synovium-lined joint, it may extend beyond the joint capsule and
      present as a soft tissue mass. Three cases of a previously unrecognized
      presentation of pigmented villonodular synovitis of the hip joint are presented.
      The authors believe these to be the first reported cases in the English language
      literature of pigmented villonodular synovitis of the hip seen with femoral or
      sciatic neuropathy.

PMID- 8998873
TI  - Anterior cruciate ligament surgery 1996. State of the art?
AB  - During the past 20 years, numerous basic science and clinical studies have
      improved the treatment of the anterior cruciate ligament deficient knee. As our
      understanding of the short term and long term morbidity caused by the torn
      anterior cruciate ligament has improved, and the morbidity of surgical
      reconstruction has decreased, the indications for anterior cruciate ligament
      reconstruction have widened. Anatomic placement of the anterior cruciate ligament
      graft has improved the outcome of surgery, although various techniques are used
      to achieve that goal. The patellar tendon autograft has been established as the
      gold standard graft choice, but several graft choices are available, and have
      given similar results in early followup. One of the major advances in anterior
      cruciate ligament reconstruction has been the acceptance of early range of motion
      and controlled endurance and strength training during the postoperative period.

PMID- 8998874
TI  - Popliteal vein thrombosis causing compartment syndrome: a case report.
AB  - Compartment syndrome as a result of venous thrombosis is an uncommon occurrence.
      Generally, phlegmasia cerulea dolens or proximal venous thrombosis results in
      elevated compartment pressures. Distal venous occlusion rarely is reported as a
      cause of compartment syndrome. This is a case report of an otherwise healthy
      patient in whom popliteal vein thrombosis developed and resulted in elevation >
      40 mm Hg of 3 leg muscle compartments requiring fasciotomies.

PMID- 8998875
TI  - Tenodesis versus carbon fiber repair of ankle ligaments: a clinical comparison.
AB  - To compare the clinical and functional outcomes after using different
      reconstruction methods for chronic ankle instability, the authors followed 2
      groups of patients after 69 and 72 months, respectively. Thirty patients (mean
      age, 28; range, 23-39 years) were treated with modified Evans tenodesis. Twenty
      three patients (mean age, 32.2; range, 22-39 years) underwent total replacement
      of the lateral ankle ligaments by carbon fibers. The protocol of the
      retrospective study included a questionnaire, clinical examination, radiographic
      stress diagnostics, and gait analysis with use of the EMED-SF system.
      Dorsiflexion and inversion were significantly restricted after tenodesis in
      contrast to the carbon fiber replacement. Although radiographic stability was
      improved after surgery for both groups, progress of the arthrosis could not be
      stopped. After tenodesis, the measurement of plantar pressure distribution
      revealed a 20% increase of midfoot loading as compared with the opposite foot,
      whereas symmetrical loading of both feet was found after carbon fiber
      replacement. Additionally, the tenodesis feet had a significantly increased
      loading of the medial side of the foot. It was concluded that tenodesis and
      anatomic reconstruction of ankle ligaments lead to subjectively similar results.
      Foot function and range of motion, however, were less influenced after anatomic
      repair.

PMID- 8998876
TI  - Editorial comment.

PMID- 8998877
TI  - Use of demineralized bone matrix in hindfoot arthrodesis.
AB  - Fifty-five patients considering a hindfoot fusion performed by the senior author
      over a 5-year period were given the choice of having the fusion augmented by
      either iliac crest bone graft or demineralized bone graft in a study of the
      relative efficacy of these 2 methods of bone grafting. Eleven patients underwent
      subtalar fusion (average age, 40.1 +/- 14.0 years), and 44 had a triple
      arthrodesis (average age, 54.6 +/- 19.2 years). The most common indications for
      surgery were posterior tibial tendon insufficiency and traumatic arthritis. There
      were no significant differences between groups regarding underlying disease,
      medications, or associated medical conditions. In isolated subtalar fusions, all
      3 patients who received an iliac crest bone graft experienced healing, as did 7
      of 8 patients who received demineralized bone graft. The eighth patient had a
      radiographic non-union without clinical symptoms. Complete healing of triple
      arthrodeses was achieved in 13 of 15 patients who received an iliac crest bone
      graft and in 29 of 29 patients receiving a demineralized bone graft. There were
      no intergroup differences in the time to union, which generally was between 3 and
      4 months. Intraoperative blood loss was significantly less with demineralized
      bone graft (33 +/- 25 ml) than with iliac crest bone graft (206 +/- 192 ml). This
      study demonstrated that demineralized bone graft aids arthrodesis at least as
      well as does iliac crest bone graft, without the increased blood loss, cost, and
      postoperative pain associated with iliac crest bone harvest.

PMID- 8998878
TI  - The effect of hallux sesamoid excision on the flexor hallucis longus moment arm.
AB  - Surgical treatments for chronic, painful hallux sesamoid disorders typically
      involve partial or complete resection of 1 or both sesamoids. Although these
      approaches generally result in satisfactory symptom relief, their effect on
      biomechanical function of the major hallux flexors is not completely understood.
      The effects of selective sesamoid resections on the effective tendon moment arm
      of the flexor hallucis longus tendon were evaluated. Twelve fresh frozen cadaver
      first rays were each mounted in a device that held rigid the metatarsal. A ramp
      controlled displacement of an MTS ram supplied a functional load input force to
      the flexor hallucis longus. The components of the resultant output force
      necessary to resist the input flexor hallucis longus force were transduced
      simultaneously by a multicomponent load cell. Subsequently, 3 progressively more
      extensive seasamoid resections were done: (1) distal hemiresection, (2) complete
      resection, and (3) resection of both sesamoids. Six specimens were tested with
      the medial sesamoid removed first and 6 with the lateral sesamoid removed first.
      Statistical analysis showed that significant decreases in the effective tendon
      moment arms occurred with full medial sesamoid resection, full lateral sesamoid
      resection, and resection of both the medial and lateral sesamoids.

PMID- 8998879
TI  - Comparison of various interpositional materials in the prevention of transphyseal
      bone bridge formation.
AB  - Various interpositional materials, except muscle, have been used to prevent
      transphyseal bone bridge formation after resection of the damaged physeal plate.
      In this animal model, muscle was used as an interpositional material, and its
      effectiveness was compared with that of 3 known materials (fat, physeal
      allograft, and iliac apophyseal autograft). Five experiments were done on the
      distal femoral physis of 40 skeletally immature 3-month-old New Zealand white
      rabbits. The rabbits were divided into 5 groups, each containing 8 rabbits. A
      standard defect was created in the lateral distal physis of the left femur in all
      the rabbits. In Group A, there was no interpositional material. Vastus lateralis
      muscle, groin fat, physeal allograft, and iliac apophyseal autograft were
      inserted into the femoral defect in Groups B, C, D, and E, respectively. The
      right femur served as a sham control for the animals. The animals were sacrificed
      at 12 weeks after surgery. The results of limb length discrepancy and angular
      deformity of the groups with interpositional material were compared with those of
      Group A (experimental control). Muscle, fat, and iliac apophyseal autografts had
      less severe limb length discrepancy and angular deformity. These differences were
      statistically significant, whereas the differences between allograft and
      experimental control were statistically insignificant.

PMID- 8998881
TI  - Ilizarov treatment of pilon fractures.
AB  - The authors retrospectively reviewed 13 pilon fractures in 12 patients treated
      with a diaphyseal-epiphyseal technique of Ilizarov external fixation. Clinical
      followup averaged 16 months (range, 12-25 months). Eighty-four percent of the
      fractures had healed within 16 weeks after surgery. Average range of motion of
      the ankle was 12 degrees dorsiflexion and 25 degrees plantar flexion. One delayed
      union was treated with bone grafting and eventually healed; 1 nonunion was
      treated with ankle arthrodesis. Most patients (91%) experienced mild or no pain.
      There were no deep infections. This technique is an effective treatment option
      for tibial pilon fractures.

PMID- 8998880
TI  - Anterior and posterior fusion for children with tuberculosis of the spine.
AB  - The authors reviewed the use of chemotherapy and anterior/posterior spinal fusion
      without instrumentation to treat children with extensive spinal tuberculosis and
      kyphosis. Six children underwent anterior and posterior spinal fusion. All of the
      patients were followed until after maturity, except for 1 child who died of
      pulmonary tuberculosis 4 months after surgery and thus was excluded from the
      study. Preoperative kyphotic deformity averaged 100 degrees (range, 75 degrees
      130 degrees). The average age at the time of surgery was 7.5 years (range, 4.7-10
      years). Spinal involvement extended from 2 to 10 vertebral bodies (average, 7.6)
      and was limited to the thoracic region from T-2 to T-12. Preoperative,
      postoperative, and followup anterior/posterior and lateral standing radiographs
      were obtained. The kyphotic angle was measured from the lateral view. The
      surgical correction of preoperative kyphosis averaged 28.6 degrees (range, 20
      degrees-45 degrees). One patient underwent repeat anterior fusion at 9 months for
      graft failure. At the time of followup, all grafts had fused and all patients
      were without pain. The average duration of followup was 12.8 years (range, 9.5
      14.5 years). Complications secondary to chronic chemotherapy occurred in 2
      children. Long-term followup revealed solid fusion, improvement of the kyphotic
      deformity, and good functional outcome in all 5 patients.

PMID- 8998882
TI  - Acute hematogenous osteomyelitis of a closed fracture with chronic
      superinfection.
AB  - Acute hematogenous salmonella osteomyelitis is rare among immunocompetent adults.
      In this study, the authors reported an unusual case of salmonella enteriditis
      osteomyelitis of the humerus complicated by methicillin-resistant Staphylococcus
      aureus superinfection and eventual chronic osteomyelitis in an immunocompetent
      host. Resection of the humeral head and a significant portion of the humeral
      shaft coupled with numerous surgical debridements and intravenously administered
      antibiotics led to resolution of symptoms. This case provides a rare example of
      acute hematogenous osteomyelitis complicating a closed fracture and demonstrates
      the difficulty associated with eradication of these specific organisms while
      emphasizing the principle of aggressive surgical debridement in cases of chronic
      osteomyelitis.

PMID- 8998883
TI  - Bilateral elastofibroma: a case report and review of the literature.
AB  - Elastofibroma, or elastofibroma dorsi as it was first described, is an uncommon
      tumor-like process that characteristically appears as an ill-defined mass in the
      infrascapular region of elderly patients. This lesion can occur bilaterally and
      may appear asynchronously. The occurrence of elastofibroma in other anatomic
      sites has been reported, although with much less frequency. Elastofibromas
      display typical diagnostic histologic, cytologic, and electron microscopic
      features. The use of magnetic resonance imaging can lead to a presumptive
      diagnosis in elderly individuals with suprascapular lesions. It is important to
      differentiate this lesion from other soft-tissue lesions, such as sarcomas and
      desmoid tumors. This study presents a case of bilateral elastofibromas in a 72
      year-old man and a review of the literature.

PMID- 8998884
TI  - Why grafts fail.
AB  - Significant advances in anterior cruciate ligament reconstructive surgery have
      been made in the past decade and, as a result, the number of anterior cruciate
      ligament reconstructive procedures being done have increased. Unfortunately,
      graft failure continues to occur and has resulted in an emphasis on revision
      surgery. Successful anterior cruciate ligament reconstruction is dependent on a
      number of factors including: patient selection, surgical technique, postoperative
      rehabilitation, and associated secondary restraint ligamentous instability. A
      particular emphasis both in scientific and clinical research has been placed on
      surgical technique. Errors in graft selection, tunnel placement, tensioning, or
      fixation methods chosen may lead to graft failure. Improper postoperative
      rehabilitation may lead to graft failure; however, current protocols seem to
      minimize its occurrence. Finally, failure to recognize or treat a significant
      secondary restraint instability can place excessive stress on the anterior
      cruciate ligament graft which may lead to failure. Care must be taken at every
      step of the process to ensure graft failure does not occur, because revision
      anterior cruciate ligament surgery results are not as predictable as primary
      anterior cruciate ligament reconstruction.

PMID- 8998885
TI  - Radiation induced malignant schwannoma arising in a neurofibroma.
AB  - Radiation induced sarcomas offer diagnostic and therapeutic challenges. The
      authors report an unusual case of radiation induced sarcoma arising 9 years after
      radiation therapy for chordoma. The location of this mass in the retroperitoneum
      and its intimate involvement with the spine raised difficult management issues.
      After limited resection was performed, consistent with the intraoperative
      diagnosis of a benign neurofibroma, foci of malignant transformation were found
      in areas of the specimen remote from the biopsy site. This complicated management
      of the sarcoma. The possibility of occult malignancy should be considered when
      evaluating tumors arising in a previously irradiated field. Thorough sampling at
      the time of biopsy is required to evaluate such lesions, particularly peripheral
      nerve sheath tumors.

PMID- 8998886
TI  - Bone transport using intramedullary fixation and a single flexible traction
      cable.
AB  - The transfixing wires used in the limb-lengthening and bone-transport procedures
      described by Ilizarov are the primary source of complications, including
      infection, restricted joint motion, and pain. In an attempt to eliminate the need
      for external fixation, a traction cable device was devised to perform a 3-cm bone
      transport in the canine femur using an interlocking intramedullary rod for
      fixation. Twelve dogs were divided into 2 groups. Transport began 7 days after
      osteotomy and continued at either 1 mm per day (n = 6) or 2 mm per day (n = 6).
      The in vivo peak force, resting force, and stiffness of the transport segment
      increased throughout distraction to a mean of 150 Newtons, 58 N, and 58 N per
      millimeter, respectively, at the time of docking. The regenerate and docking
      sites united in 10 of 12 dogs. Failure of the regenerate associated with deep
      infection around the rod occurred in 2 animals (17%). Modifications of this
      technique to reduce the risk of infection are discussed. This study confirms that
      intramedullary fixation is compatible with distraction osteogenesis and shows
      that a single traction cable can provide the force necessary for bone transport
      without transfixing wires in this setting.

PMID- 8998887
TI  - Hydroxyapatite coated external fixation pins: an experimental study.
AB  - A sheep model was developed for the implantation of 84 bicylindrical stainless
      steel external fixation pins. One-half of the pins were coated with
      hydroxyapatite, and the rest remained uncoated. A set of 6 pins with the same
      coating was implanted in the lateral side of the left tibias of 14 sheep, the
      final insertion torque was measured, and a monolateral external fixator was
      assembled on the pins. The medial tibial middiaphysis then was exposed and a 5-mm
      resection osteotomy was done. Sheep were euthanized 6 weeks after surgery,
      radiographs were taken, and the initial extraction torque was measured on 4 pins
      from each sheep. Undecalcified sectioning and histologic and histomorphometric
      analyses were done on the remaining 2 pins. Radiographic pin tract rarefaction
      was significantly lower in the hydroxyapatite coated pins compared with the
      uncoated pins. Group average insertion torque was 960 +/- 959 Nmm in the
      hydroxyapatite coated pins and 709 +/- 585 Nmm in the uncoated pins. Group
      average initial extraction torque was 1485 +/- 1308 Nmm and 298 +/- 373 Nmm,
      respectively. Bone pin contact was 85.7% +/- 8.9% and 50.3% +/- 20.4%,
      respectively, in hydroxyapatite coated and uncoated pins. Bone between the
      threads was 95.6% +/- 5.7% and 80% +/- 8.7%, respectively, in hydroxyapatite
      coated and uncoated pins. Hydroxyapatite coating was effective for improving the
      bone-to-pin interface.

PMID- 8998888
TI  - Micromotion, fit, and fill of custom made femoral stems designed with an
      automated process.
AB  - This study presents an automated process for the design of custom made femoral
      stems. Two software programs have been developed to obtain the inner bone
      contours from computed tomography scan images and to design the optimal stem that
      can be inserted into the femur. This process requires only 2 hours of computer
      use, therefore reducing the price of the stem. It is also possible to control the
      amount of bone sacrifice necessary to facilitate the insertion of the stem.
      Micromotion for 6 specimens was measured using a special machine simulating the
      load supported by the hip joint during single-limb stance. Three prostheses were
      tested successively: anatomic cementless stem, custom made stem, and modified
      custom made stem in which the distal part was thinned out. To be stabilized, the
      anatomic prosthesis required a greater number of cycles than custom made stems
      associated with a more important total vertical migration. The micromotion of
      custom made prostheses was significantly less than that of the other prostheses.
      The fill of custom made stems also was measured, having a range from 93% to 100%
      (mean, 97.5%-98.8%) of the medullary canal. The metaphyseal fill was
      significantly linked with the vertical and rotational components of instability.
      These results showed that it was possible, using a computerized automated and
      controlled process, to obtain low price femoral stems well fitted to the
      medullary canal that provide an excellent primary stability.

PMID- 8998889
TI  - Contact features of the talonavicular joint of the foot.
AB  - Seven cadaveric feet were studied to determine the distribution of the contact
      area of the talonavicular joint. Feet were loaded axially with soft tissue
      structures intact and after sectioning of static elements that support the arch.
      Bony displacement was monitored with a magnetic tracking device, and joint
      contact was determined from proximity calculations of digitized joint surfaces.
      With physiologic loading of the intact foot, the number of regions in contact
      increased. In the unstable foot, there was a shift in contact distribution toward
      more dorsal and central regions of the navicular bone. This is consistent with
      the clinical observation that fatigue fractures, acute fractures, and nonunion of
      navicular fractures occur often in the central navicular body. The alteration in
      contact characteristics in unstable feet is also consistent with the observation
      that osteoarthrosis of the hindfoot joints occurs commonly with long-standing
      arch instability or pes planus deformity.

PMID- 8998890
TI  - Internal fixation of oblique metacarpal fractures. A biomechanical evaluation by
      impact loading.
AB  - Internal fixation of oblique metacarpal fractures was studied in a cadaver model
      by impact loading. One hundred twenty fresh-frozen human metacarpals underwent
      compressive and bending impacts after oblique osteotomy and internal fixation.
      Dorsal plating with lag screws, 2 dorsal lag screws (2-screws), crossed Kirschner
      wire tension band (crossed K-wire), 5 stacked intramedullary Kirschner wire (5
      rod), and paired intramedullary Kirschner wire (2-rod) were used. The failure
      occurred within 6 msec in the compressive impact and was almost immediate in the
      bending impact. The dorsal plate and the intramedullary rod fixations were the
      strongest and were not significantly different from the intact specimens in
      compressive impact; they were, however, 19% weaker in bending impact. The 2
      screws was the weakest fixation in this group. This fixation was 59% weaker in
      compressive impact and 47% weaker in bending impact compared with the dorsal
      plating.

PMID- 8998891
TI  - Ketorolac versus meperidine for pain relief after orthopaedic surgery.
AB  - In this double-blind, randomized, multicenter study, 244 patients with at least
      moderate pain after major orthopaedic surgery received intramuscular Ketorolac
      (60 mg followed by 30 mg) or intramuscular meperidine (100 mg or placebo) every 2
      to 6 hours as needed for as many as 5 days. Analgesic response was evaluated for
      6 hours after initial study drug administration and thereafter each night at
      bedtime. Both active treatment groups had similar 3-hour summed pain intensity
      difference and 3-hour total pain relief scores after the first dose that were
      superior to placebo. The 6-hour summed pain intensity difference and total pain
      relief scores were significantly higher with Ketorolac than with meperidine or
      placebo. The mean daily categorical pain intensity scores were comparable with
      Ketorolac and meperidine, and both were significantly superior to placebo.
      Patient ratings of overall medication efficacy were significantly better with
      Ketorolac than with meperidine. In both patient and observer evaluations,
      Ketorolac was significantly better tolerated than meperidine, and the number of
      patients reporting adverse events was lower with Ketorolac than with meperidine.
      Following major orthopaedic surgery, Ketorolac provided effective analgesia that
      was superior to placebo and at least comparable with meperidine. Ketorolac was
      better tolerated than meperidine.

PMID- 8998892
TI  - Prevention of venous thromboembolism in orthopaedics in the United States.
AB  - The use of different types of antithrombotic prophylactics in various clinical
      settings was examined. A standardized questionnaire was mailed to 5000 randomly
      selected practicing orthopaedic surgeons that detailed practice profile, surgical
      case type and frequency, method of thromboembolism prophylaxis used, incidence of
      morbidity, and type of screening used. Twenty-one percent (n = 1046) of surgeons
      surveyed returned the questionnaire. Four of 5 surgeons performing elective hip
      arthroplasty used some form of thromboembolic prophylaxis for all of their
      patients, 13% used prophylaxis only for patients considered to be at high risk,
      and 3% of respondents never used prophylaxis. The rates of prophylactic use for
      patients undergoing elective knee arthroplasty were similar. A considerably lower
      rate of routine prophylactic use was seen among surgeons performing surgery for
      pelvic and lower extremity trauma. Except for cases involving neurologic
      compromise, most patients undergoing either elective or traumatic spinal surgery
      were not given prophylaxis. Low dose warfarin alone was the most commonly used
      prophylaxis modality. A comparison of the results of the current survey with
      those of past surveys showed that the use of aspirin has fallen. The use of
      routine pharmacologic prophylaxis against thromboembolism in hip and knee
      arthroplasty has become the standard of care in the United States. Among patients
      undergoing surgery for hip fracture and other lower extremity trauma, however,
      prophylaxis remains underused.

PMID- 8998893
TI  - Intoeing in a 14-year-old girl.

PMID- 8998894
TI  - Osteoid osteoma of the hip. Percutaneous resection guided by computed tomography.

PMID- 8998895
TI  - Cementless femoral components should be made from cobalt chrome.

PMID- 8998896
TI  - The Nicolas Andry award: comparative results of cemented and cementless total hip
      arthroplasty.
AB  - A prospective randomized clinical trial comparing cemented to cementless total
      hip arthroplasty has been ongoing at the author's institution since 1987. All
      parameters assessed showed that there was no statistically significant difference
      in any of the health related quality of life measures used when patients with
      cement were compared with patients without cement at any of the followup periods
      as many as 4 years later. The improvement was dramatic and sustained. No
      components (cemented or cementless) have been revised to date (average, 4.8
      years). A radiographic analysis showed probable loosening of the cemented socket
      in 24% and presumed minimal pelvic osteolysis in 8%. The cementless sockets
      showed a greater frequency and severity of pelvic osteolysis (14%). The cemented
      femoral component was judged to be possibly loose in 10%; however, none were
      considered probably loose. The patients who had cementless femoral components
      were doing extremely well with the components showing very little subsidence or
      proximal stress protection noted. Osteolysis on the femoral side was not seen in
      any of the cementless stems. Total hip replacement gives comparable clinical
      results when health related quality of life measures are analyzed; however, metal
      backed cemented acetabular components have a high rate of radiographic failure.
      Short-term stability of a non-cemented porous coated titanium stem, however, gave
      excellent clinical and radiographic results.

PMID- 8998897
TI  - Isolated tear of the anterior cruciate ligament: 5-year followup study.

PMID- 8998899
TI  - Technical considerations of revision anterior cruciate ligament surgery.
AB  - Revision anterior cruciate ligament surgery will become more common as the number
      of primary anterior cruciate ligament reconstructions increases. Also
      contributing to this increase are those patients who had anterior cruciate
      ligament reconstruction using synthetic ligaments and other nonanatomic
      techniques that are no longer used. Preoperative planning is imperative to a
      successful outcome. This begins with determining the primary, and often times
      secondary, mechanism of failure for each patient. The determination of the
      etiology of failure is the first step in a carefully constructed preoperative
      plan, including the type of revision, skin incision, graft removal, hardware
      removal, tunnel placement, graft selection, graft fixation, and rehabilitation.
      The precise preoperative plan should have enough flexibility to accommodate
      unanticipated findings in the operating room. Rehabilitation protocols must be
      designed specifically for the revision surgery patient and be flexible enough to
      accommodate changes based on surgical findings and techniques. Finally, the
      importance of counseling the patient preoperatively regarding the potential
      results which, in general, are somewhat less satisfactory than with most primary
      reconstructions, must be emphasized. However, with proper planning, attention to
      detail, and adherence to basic principles of anterior cruciate ligament
      reconstruction, revision anterior cruciate ligament surgery can provide a
      satisfying solution to difficult knee instability cases.

PMID- 8998898
TI  - Failure of anterior cruciate ligament reconstruction: the biologic basis.
AB  - The replacement tissue used for anterior cruciate ligament reconstruction
      undergoes extensive biologic remodeling and incorporation after implantation.
      Successful biologic incorporation of the graft is dependent on a number of
      factors including graft placement, tensioning, and the nature of the tissue
      (allograft versus autograft). Failure of an anterior cruciate ligament
      reconstruction may occur on the basis of either technical, mechanical, or
      biological factors. Biologic factors include cellular repopulation, matrix
      remodeling, the ultimate small diameter collagen fibril orientation, the final
      cross sectional area of the graft, a favorable vascularization, and not
      overloading the graft during the remodeling process. The fully incorporated graft
      never duplicates the native anterior cruciate ligament but works as a check reign
      that makes the knee more functional.

PMID- 8998900
TI  - Graft selection in anterior cruciate ligament revision surgery.
AB  - Revision anterior cruciate ligament surgery can be very demanding. Graft
      selection for revision surgery is a pivotal part of this procedure. Often, the
      usual first choice of tissue is not available. Therefore, familiarity with
      alternative graft sources and understanding their advantages and disadvantages is
      imperative for the surgeon who does anterior cruciate ligament revision surgery.
      This study will review the advantages and disadvantages of each graft choice
      available to the surgeon for this procedure.

PMID- 8998901
TI  - Revision of failed prosthetic anterior cruciate ligament reconstruction.
AB  - Revision of failed prosthetic anterior cruciate ligament reconstructions will
      continue to be necessary as previously placed prosthetic devices fail with time.
      These patients often present with recurrent instability, pain, swelling, or
      effusions. Graft rupture and the generation of particulate debris are common
      causes of these symptoms. To effectively treat these patients requires careful
      preoperative evaluation and planning. Operative treatment includes removing the
      prosthesis and metal fixation devices, evaluating femoral and tibial bone stock,
      and determining adequacy of previous tunnel position. Staging of the operation
      may be a necessity if significant bone loss or poor tunnel position on either the
      femoral or tibial side requires bone grafting. The use of an autogenous bone
      patellar tendon-bone graft is suggested and has proven to be effective in
      restoring knee stability in these revision cases. The ultimate outcome following
      revision of failed prosthetic ligaments may be limited by associated
      intraarticular pathology often seen in this patient population.

PMID- 8998902
TI  - Revision anterior cruciate ligament surgery: experience from Miami.
AB  - Failed anterior cruciate ligament reconstruction as defined by recurrent
      patholaxity is increasingly commonplace. This report presents the findings of 54
      patients who had unsuccessful intraarticular anterior cruciate ligament
      reconstruction to correct persistent instability and who subsequently underwent
      revision anterior cruciate ligament surgery. Before revision, patients were
      evaluated by clinical examination, KT-1000 arthrometer, radiographs, Lysholm knee
      score, Tegner activity scale, and subjective questionnaire. The results were
      compared at a mean of 32 months following revision surgery. There was an average
      of 16 months from index procedure to the time of revision. Autogenous patellar
      tendon grafts were used in 61% of the cases with 30% of these harvested from the
      contralateral knee. Fresh frozen patellar tendon was used in 35% and autogenous
      hamstring tendons in 4%. Revision was successful in objectively improving
      stability in all patients with an average KT-000 of 2.8 mm. Autogenous tissue
      grafts provided greater objective stability when compared with allograft tissue
      with average KT-1000 of 2.2 and 3.3, respectively. Functionally, however, there
      was no significant difference in outcome between the 2 groups. Harvesting of the
      contralateral patellar tendon was found to have no adverse long term effect.
      Subjectively, the results were significantly worse depending on the degree of
      articular cartilage degeneration. Only 54% of patients returned to their
      preanterior cruciate ligament injury activity level. Competence in various
      anterior cruciate ligament reconstruction techniques will facilitate revision
      surgery especially in avoiding preexisting tunnels and hardware. Correct graft
      placement and addressing the secondary restraints are critical to successful
      revision surgery.

PMID- 8998903
TI  - "1-800-DENIED".

PMID- 8998904
TI  - Primary-care quality improvement of mammography rates: a baseline study.
AB  - In order to improve mammography screening rates, a primary-care physician group
      in Hartford County studied mammogram compliance rates, and reasons for
      noncompliance, in a group of 722 women, aged 50 to 64 years. RESULTS: During the
      two-year study period, 598 (82.8%) of the patients had a mammogram and 16 were
      lost to follow-up. Of the 108 women without mammograms, six did not think that
      one was recommended. The test was not indicated for four. Forty did not follow
      through with recommendations, nine avoided mammograms out of fear, and 11 refused
      mammograms or physician visits. Thirty-seven others had a mammogram scheduled or
      performed during the next year. CONCLUSIONS: Several hypothetical strategies for
      improving compliance are suggested by these results: computer notification of
      patients of upcoming and overdue due dates, supportive exploration of patients'
      resistances and fears, phone reminders from primary care physician offices,
      preventive medicine "tickler files," and coordination across specialties.

PMID- 8998905
TI  - Estimating breast cancer treatment charges in Connecticut.
AB  - Previous studies of estimated costs for cancer treatment have been limited to
      elderly patients or to specific health maintenance organizations. Data from the
      statewide population-based Connecticut Tumor Registry on a random sample of 407
      breast cancer patients diagnosed in 1991 were linked with a statewide hospital
      discharge database, to estimate charges (through September 1993) for inpatient
      and ambulatory surgery care. For the 377 cases (92.6% of 407) successfully
      linked, average charges attributed to breast cancer care declined with age,
      increased with extent of disease (stage at diagnosis), and increased with extent
      of surgery; these associations persisted in multivariate analyses. Total hospital
      related charges for comorbid conditions (during 1991-93) were considerable by age
      45 to 64 years. The merged database should be most useful in estimating charges
      for: cancers treated mainly by surgery (including ambulatory surgery at
      hospitals); comorbid conditions; and terminal care.

PMID- 8998906
TI  - Losartan (Cozaar)

PMID- 8998907
TI  - The patient-physician covenant: an affirmation of Asklepios.
AB  - Medicine is, at its center, a moral enterprise grounded in a covenant of trust.
      This covenant obliges physicians to be competent and to use their competence in
      the patient's best interests. Physicians, therefore, are both intellectually and
      morally obliged to act as advocates for the sick wherever their welfare is
      threatened and for their health at all times. Today, this covenant of trust is
      significantly threatened. From within, there is growing legitimation of the
      physician's materialistic self-interest; from without, for-profit forces press
      the physician into the role of commercial agent to enhance the profitability of
      health care organizations. Such distortions of the physician's responsibility
      degrade the physician-patient relationship that is the central element and
      structure of clinical care. To capitulate to these alterations of the trust
      relationship is to significantly alter the physician's role as healer, carer
      helper, and advocate for the sick and for the health of all. By its traditions
      and very nature, medicine is a special kind of human activity--one that cannot be
      pursued effectively without the virtues of humility, honesty, intellectual
      integrity, compassion, and effacement of excessive self-interest. These traits
      mark physicians as members of a moral community dedicated to something other than
      its own self-interest. Our first obligation must be to serve the good of those
      persons who seek our help and trust us to provide it. Physicians, as physicians,
      are not, and must never be, commercial entrepreneurs, gateclosers, or agents of
      fiscal policy that runs counter to our trust. Any defection from primacy of the
      patient's well-being places the patient at risk by treatment that may compromise
      quality of or access to medical care. We believe the medical profession must
      reaffirm the primacy of its obligation to the patient through national, state,
      and local professional societies; our academic, research, and hospital
      organizations; and especially through personal behavior. As advocates for the
      promotion of health and support of the sick, we are called upon to discuss,
      defend, and promulgate medical care by every ethical means available. Only by
      caring and advocating for the patient can the integrity of our profession be
      affirmed. Thus we honor our covenant of trust with patients.

PMID- 8998908
TI  - Academic health centers and managed care.

PMID- 8998909
TI  - The primary physician and the family with a handicapped or chronically ill child.

PMID- 8998910
TI  - Primary care continuing medical education and managed care.

PMID- 8998911
TI  - Rule 6, never take yourself seriously.

PMID- 8998912
TI  - Antiplatelet activity of cis-resveratrol.
AB  - The anti-aggregating effect of cis-resveratrol (cis-3,4,5- trihydroxystilbene)
      has been evaluated in vitro in different concentrations on platelet-rich plasma
      from health volunteers. Cis-resveratrol at the concentration of 1 x 10(-5) and 1
      x 10(-6) M was able to decrease collagen-induced platelet aggregation by 43.5 +/
      11.4% and 26.8 +/- 14.6%, while trans-resveratrol at the same concentration
      showed a slightly lower activity. In view of the behaviour of these two isomers
      in biological fluids, the evaluation of resveratrol activity in animals and
      humans take into account the total amount of the two isomers.

PMID- 8998913
TI  - [What do HIV patients expect from their physician?].

PMID- 8998914
TI  - [HIV: less resistance due to combined treatment].

PMID- 8998915
TI  - [Nevirapine: a new principle of action against HIV].

PMID- 8998916
TI  - [HIV: to administer protease inhibitors early].

PMID- 8998917
TI  - [AIDS Congress in Munich: "On the road to the breakthrough"].

PMID- 8998918
TI  - [AIDS: one pandemic or many epidemics?].

PMID- 8998919
TI  - [Pneumococcal vaccination after heart and liver transplantation. Immune responses
      in immunosuppressed patients and in healthy controls].
AB  - BASIC PROBLEM AND OBJECTIVE OF STUDY: Among other effects, therapeutic
      immunosuppression after organ transplantation impairs antibody formation. But
      because of the increased risk of infection, the efficacy of prophylactic
      immunization is of particular importance in patients after transplantation. For
      this reason the immunogenicity after immunization against pneumococcus was
      investigated in transplanted patients. PATIENTS AND METHODS: A 23-valent vaccine
      of capsular polysaccharides (Pneumovax 23) was administered to 31 patients 4-85
      months after transplantation (16 hearts transplants, 15 liver transplants; age
      range 22-63 years). The same immunization was given to 23 healthy control
      subjects. The immune response was measured serologically in all groups. RESULTS:
      Immunization was well tolerated by all participants, and there were no infectious
      or systemic side effects. Mean postvaccinal global pneumococcus-specific antibody
      titres were comparable in the healthy and transplanted subjects (controls: 5490
      U/ml, heart transplanted: 5513 U/ml, liver transplanted: 4148 U/ml; differences
      not significant). Analysis of individual titres for the nine most important
      serotypes showed comparable results for six serotypes, reduced titres being found
      for serotypes 3 and 8 after heart transplantation, and for serotypes 8 and 23
      after liver transplantation. CONCLUSION: Safe antipneumococcal immunization is
      possible during therapeutic immunosuppression after heart or liver
      transplantation. The achieved immune response is comparable to that in healthy
      controls. The high efficacy of the pneumococcal vaccine, compared with other
      vaccines, in immunosuppressed patients may be due to T-cell dependent antibody
      production against polysaccharides.

PMID- 8998920
TI  - [Percutaneous nephrostomy in malignant ureteral obstruction].
AB  - OBJECTIVE: To assess survival length and quality of life in patients with a
      percutaneous nephrostomy (PN) for malignant tumour and postrenal anuria. PATIENTS
      AND METHODS: Case records were analysed of 50 patients (39 men, eleven women;
      mean age 65.6 years) with postrenal anuria due to malignancy who had undergone
      ultrasound-directed PN under local anaesthesia for urinary drainage. Particular
      attention was paid to the course of the disease from nephrostomy until death.
      RESULTS: Survival time after PN ranged from 4 days to 16 months, averaging 4.3
      months. 26 patients (52%) had died after 3 months, 41 (82%) after 6 months. The
      patients had spent on average 44.5% of their remaining life in hospital. After an
      initial improvement in their state, cancer-produced pain and complications soon
      set in and often required operative intervention. CONCLUSION: The achieved
      prolongation of survival time did not always meet the patient's own wishes.
      Detailed explanation and information to patient and family before PN is therefore
      urgently required.

PMID- 8998921
TI  - [Endosonographic demonstration of extrapancreatic and extraintestinal
      gastrinoma].
AB  - HISTORY AND CLINICAL FINDINGS: No cause had been found for chronic diarrhoea in a
      57-year-old man. Up to 15 watery stools daily had been without relation to food
      intake and without blood admixture. But muscular cramps had developed, especially
      in the legs. The patient had a history of recurrent peptic ulcers for which a
      selective proximal vagotomy had been performed 13 years ago. Physical examination
      was unremarkable. INVESTIGATIONS: Alkaline phosphatase activity (182 U/l) and C
      reactive protein (9.3 mg/l) were slightly raised; serum iron was 42
      micrograms/dl, while all other routine laboratory tests, including protein
      electrophoresis, blood picture and differential count were within normal limits.
      Gastroscopy revealed ulcerative duodenitis, gastritis with erosions and numerous
      ulcers and reflux oesophagitis, grade III-IV. Endosonography showed enlarged
      gastric mucosal relief as sign of foveolar hyperplasia and a ca. 4 x 3 cm tumour
      next to the duodenal bulb. Gastrin level was 7537 pg/ml (normal < 150 pg/ml).
      Computed tomography and somatostatin receptor scintigraphy confirmed the site and
      size of the gastrinoma. TREATMENT AND COURSE: Treatment with omeprazole (40 mg
      three times daily) slightly improved the symptoms. The tumour was excised a week
      after diagnosis. The patient has been symptom-free since then. CONCLUSION:
      Chronic diarrhoea of unknown aetiology can be caused by an endocrine tumour;
      endosonography can often provide information on the diagnosis and location of
      such a tumour.

PMID- 8998922
TI  - [Therapy of autoimmune hepatitis].

PMID- 8998923
TI  - [Thromboangiitis obliterans (Buerger's syndrome): clinical aspects, diagnosis and
      therapy].

PMID- 8998924
TI  - [Release from the buckle-up duty].

PMID- 8998925
TI  - [Acetylcysteine].

PMID- 8998926
TI  - [Tuberculosis of the middle ear: a rare extrapulmonary manifestation].

PMID- 8998927
TI  - [Decision to use complementary medicine: fact oriented or irrational?].
AB  - PROBLEM AND OBJECTIVE: Complementary medicine is being used to varying extent in
      all industrial countries. There are incomplete data concerning efficacy, safety
      and costs of such treatment, while little is known about special features and
      motivation of those persons who choose complementary medicine. The aim of the
      study was to ascertain, among patients who use complementary medicine and those
      who prefer traditional medicine, any differences with regard to sociodemographic,
      disease-related and psychological characteristics and their life-style. PATIENTS
      AND METHODS: A total of 419 patients were studied by a standardised interview and
      questionnaire (168 items) and divided into two groups (group 1: those using
      conventional treatment [n - 197; 91 women, 106 men; average age 43.2 +/- 16.9
      years]; group 2: those preferring complementary medicine [n = 222; 159 women, 63
      men; average age 43.2 +/- 15.0 years]). They were recruited from specialist
      internal medical or generalist medical practice with or without offer of
      complementary medicine (additional term: natural healing methods). Statistical
      analysis was with Student's-t-test and the chi(2)-test [correction of gamma
      test]. RESULTS: Those patients who chose to be treated by complementary medicine
      clearly differed from the others with respect to sociodemographic, disease
      related and psychological characteristics, as well as life-style. The patient
      doctor relationship also differed between the two groups. On average those of
      group 2 had a higher educational level (higher education: 10.3% in group 1; 15.9
      in group 2) and lower risk factors (68.9% nonsmokers in group 1, 77.8% in group
      2; alcohol abstinence: 33.2 vs 46.4%). Patients in both groups preferred
      conventional medicine for serious diseases (cardiac infarct; tumour; AIDS).
      CONCLUSIONS: In general, those patients who choose complementary medicine have a
      healthier life-style. As the number of these patients is on the increase. Since
      as yet the efficacy, risks and costs of complementary medicine have been
      inadequately investigated, research in this area should be intensified.

PMID- 8998928
TI  - [English or German? The language of medicine based on the bibliographic data
      appearing in the Deutsche Medizinische Wochenscrift (1920 to 1995)].
AB  - AIM OF STUDY: To describe and analyse the frequency of English and German in the
      bibliographical references from the original articles published in "Deutsche
      Medizinische Wochenschrift" during the past 75 years (1920-1995). METHODS: The
      language of publication of 16,001 references from 800 original papers, at the
      rate of 50 articles per year at intervals of 5 years, was determined. RESULTS:
      The percentage of references in German has been decreasing during the whole
      studied period: 90.1% in 1920, 85.9% in 1935, 75.8% in 1950, 44.1% in 1965, 31.0%
      in 1980, and 16.4% in 1995. The percentage of references in English, on the
      contrary, has continued to increase: 3.2% in 1920, 10.6% in 1935, 21.5% in 1950,
      50.0% in 1965, 66.2% in 1980, and 82.8% in 1995. CONCLUSION: Even though the
      importance of English has been increasing during the entire considered period, it
      did not clearly supplant German as the main language of medicine in Germany until
      1975.

PMID- 8998929
TI  - [Ruptured pseudoaneurysm of the splenic artery. A complication of chronic
      pancreatitis].
AB  - HISTORY AND FINDINGS: A pale looking 33-year-old man with a history of perforated
      gastric ulcer and pancreatitis with surgically drained pseudocyst was admitted
      because of painless anal bleeding. Heart rate was 100/min, blood pressure 90/60
      mm Hg. INVESTIGATIONS: Haemoglobin concentration (6.3 g/dl) and RBC count (2.4
      mill./microliters) indicated anaemia due to bleeding. Sonography and computed
      tomography demonstrated chronic calcifying pancreatitis and thrombosis of splenic
      and mesenteric veins. There were grade 1 oesophageal varices on endoscopy. The
      source of bleeding was found by coloscopy to be a submucous pulsating tumour in
      the region of the left flexure, which on angiography was an aneurysm of the
      splenic artery. TREATMENT AND COURSE: The pseudoaneurysm of the splenic artery,
      which had perforated into the colon, was resected together with a partial
      pancreas excision and splenectomy. There were no complications and the patient
      was discharged symptom-free after 15 days, and there had been no further bleeding
      6 months later. CONCLUSION: Pseudoaneurysm of a visceral artery is a rare, but
      life-threatening, complication of pancreatitis. Treatment options are operation
      and/or interventional catheter embolisation.

PMID- 8998930
TI  - [Malignant melanoma of the esophagus and anorectum].

PMID- 8998931
TI  - [Antimalarial agents in rheumatic diseases. New therapeutic aspects of an old
      medication].

PMID- 8998932
TI  - [Estrogen deficiency after hysterectomy without ovariectomy].

PMID- 8998933
TI  - [Public killing of infants].

PMID- 8998934
TI  - [Quality assurance in colonoscopy in practice and clinical medicine].

PMID- 8998935
TI  - [Supervision of distribution and use of veterinary drugs in Schleswig-Holstein].
AB  - By means of drug related legislation the endowment and limits of veterinary
      medicines surveillance are demonstrated. The distribution of veterinary
      pharmaceutical products is organised in wide area structures, both in legal and
      illegal employment. Thus powerful monitoring can only be established by co
      operation of all involved institutions. In advance, a concentration of duties in
      a few administrations with supraregional authorisation can take place, in
      particular shown here for the organisation of the recommended institutions in
      Schleswig-Holstein. A catalogue of typical violations und neglects indicates
      areas of problems at various levels of veterinary drug trade (production,
      distribution, pharmacy, veterinarian). A report about the performance and results
      of the surveillance of drug applications in animal production demonstrates the
      conjoint consummation of drug control in farms and specimen control on living and
      slaughtered animals.

PMID- 8998936
TI  - [The use of feed medications in swine and poultry facilities in the Weser-Ems
      region].
AB  - The use of medicated feed notably in large pig and poultry holdings is a major
      aspect of veterinary treatment against infectious diseases. Every single
      production of a medicated feed requires a specified written authorization by the
      veterinary practitioner and a carbon copy of this document must be sent to the
      responsible veterinary public health office. These documents-in the Weser-Ems
      region up to ca. 30,000 per annum-were entered into a computer database and
      analysed. The results are presented as diagrams and graphs. Information on the
      quantities of the various administered drug constituents is also included. With
      regard to current risks concerning residues and resistances the data gives
      qualified information on the per os treatment with antibiotics of food producing
      animals.

PMID- 8998937
TI  - [Risks due to the medication of feed and water in animal facilities].
AB  - Goal of this contribution was a review concerning the different risks of
      application of drugs in food producing animals, excluding the development of
      resistance in pathogenic bacteria. Especially the risks of displacements of drugs
      and additives during the process of production of medicated feeds and its use
      under field conditions are concerned. Furthermore water medication and its
      problems of risks are presented. The onset of drug residues in food--inspite of
      the use of unmedicated feeds and water--is discussed for example as a consequence
      of contamination of feeds (especially in wet feeding systems in pigs), the
      surrounding and/or litters.

PMID- 8998938
TI  - [Development of resistance in infectious agents of agricultural animals in
      Germany (1990-1994)--a review].
AB  - Antibiograms received from veterinary laboratories during the 1990-1994 period
      were recorded and evaluated with the aid of a computer program. Based on 70
      tables giving information about th most important pathogens, the resistance
      behaviour of E. coli in cattle, swine, chicken, and turkey, that of Pasteurella
      haemolytica and P. multocida in cattle and swine and that of Staphylococcus
      aureus and Streptococcus agalactiae in cattle have been in synoptic form.
      Attention is drawn to the increase in resistance to enrofloxacin shown by E.
      coli, particularly in turkeys.

PMID- 8998939
TI  - [Development of resistance to antiparasitic agents in parasites pathogenic to
      animals].
AB  - Drug resistance of parasites is a worldwide problem of increasing importance in
      animal production. Considerable information is available on the development of
      resistance in chicken coccidia and in strongyles of horses, sheep, goats and
      pigs. A review is given of the development, incidence, and management of drug
      resistance with emphasis on the situation in Germany.

PMID- 8998940
TI  - [Effects of residues of anti-infective agents in animal excretions on slurry
      treatment and the soil].
AB  - Application of antibiotics and feed additives in animal husbandry generates
      populations of resistant bacteria in the gut which are introduced via slurry into
      the ecosystem soil. Nevertheless the influence to the ecosystem soil seems to be
      low, due to inactivation and dilution in slurry and soil. The probability that
      this pathway contributes to the problems of antibiotic resistance in human
      medicine is low. Aerobic and anaerobic treatment of slurry is more or less
      influenced by residuals of some feed additives and antibiotics. The aerobic
      thermophilic treatment seems generally to be more sensitive than the anaerobic
      biogas production, except in some special cases. No evidence could be found that
      residuals of antibiotics in slurry have a negative influence on the ecosystem
      soil, due to preliminary results obtained by similar field trials with
      disinfectants. The application of antibiotics in aquaculture must be regarded
      more critically.

PMID- 8998941
TI  - [Parasite control and its effect on the environment].
AB  - Chemical methods continue to be the primary means for control of parasites in
      medicine and veterinary medicine. Environmental concerns are raised mainly in the
      control of free living stages of parasites, intermediate hosts, vectors of
      diseases and in control of sanitary pests. Similarly, the type of application in
      case of sheep-dips and spraying of acaricides and insecticides in poultry houses
      against chicken mites is problematical. The now available bolus with ivermectin
      may cause a stronger impact on the cattle dung fauna and subsequent degradation
      of the dung as already known after injection and pour on.

PMID- 8998942
TI  - [The distribution of antibiotically-resistant organisms in the environment with
      special attention to salmonellae].
AB  - Antibiotic resistant determinants (R) prevail in environmental bacteria
      independent of antibiotic application in human and veterinary medicine als well
      as in agriculture. Due to horizontal gene transfer (plasmids) the spread of R.
      determinants to pathogenic bacteria occur in relation to selection pressure.
      Since salmonella bacteria have been found to persist in environmental habitats
      for a long time they will serve as recipients as a reservoir (donors).

PMID- 8998944
TI  - Infectious diseases: Basel Research Forum International. Basel, Switzerland, 4 -
      5 September 1995. Proceedings.

PMID- 8998943
TI  - [Health and environmental risks after the use of anti-infective agents and
      antiparasitic agents in domestic animal husbandry--avoidance strategies and ways
      out].
AB  - At the beginning, the field of controversy is described, in which the usage of
      antimicrobials and antiparasitics are discussed, and the areas of their every day
      application are analysed. Based on the evaluation of the individual kinds of
      application of antimicrobial substances, conclusions for their usage are drawn,
      with their total avoidance not being the ultimate goal, but the scientifically
      founded use of these valuable substances according the the principle: 1. tailored
      to the correct diagnosis and 2. as little as possible, but always the amount that
      is needed.

PMID- 8998945
TI  - Workshop overview. National Toxicology Program Studies: principles of dose
      selection and applications to mechanistic based risk assessment.
AB  - A workshop entitled "NTP Studies: Principles of Dose Selection and Applications
      to Mechanistic Based Risk Assessment" was held at the 34th Annual Meeting of the
      Society of Toxicology in Baltimore, Maryland. The purpose of the workshop was to
      provide an overview of factors currently considered important in the selection of
      doses for NTP studies, to describe some of the confounding factors that can
      result from the indiscriminate use of bioassay data in quantitative risk
      assessment, and to suggest ways in which information from mechanistic studies or
      studies of biomarkers of exposure or effect might be used to better advantage in
      risk assessment.

PMID- 8998946
TI  - DNA-protein cross-links (DPX) and cell proliferation in B6C3F1 mice but not
      Syrian golden hamsters exposed to dichloromethane: pharmacokinetics and risk
      assessment with DPX as dosimeter.
AB  - Dichloromethane (DCM) (methylene chloride; CH2Cl2) is metabolized via a
      glutathione S-transferase-mediated pathway to formaldehyde (HCHO), a mutagenic
      compound that could play a role in the carcinogenic effects of DCM observed in
      the liver and lungs of B6C3F1 mice at 2000 and 4000 ppm. Mice but not hamsters
      formed DNA-protein cross-links (DPX) in the liver at DCM concentrations ranging
      from approximately 500 to 4000 ppm. The formation of DPX was a nonlinear function
      of the airborne concentration of DCM. In addition, mice exposed to DCM (6 hr/day,
      3 days) at concentrations ranging from approximately 1500 to 4000 ppm showed an
      increased rate of DNA synthesis in the lung indicating cell proliferation, but
      increased cell turnover was not detected in mouse lung at exposure concentrations
      of 150 or 500 ppm. Hamsters showed no evidence of cell proliferation in the lung
      at any concentration, and cell proliferation was not apparent in the livers of
      either mice or hamsters. An extended physiologically based pharmacokinetic (PBPK)
      model for DPX formation in mouse liver was developed, based on a published PBPK
      model for DCM (Andersen, M.E., Clewell, H.J., III, Gargas, M.L., Smith, F.A., and
      Reitz, R.H. (1987). Toxicol. Appl. Pharmacol. 87, 185-205). The extended PBPK
      model was fitted to the DPX data using the PBPK model-estimated area under the
      curve for DCM in mouse liver as the independent variable. Parameter estimates for
      HCHO disposition in the livers of mice exposed to dichloromethane were similar to
      previously published estimates for HCHO disposition in the nasal mucosa of rats
      exposed to formaldehyde. Using the extended PBPK model, estimates were made of
      the yields of DPX presumably formed in mouse liver at the DCM concentrations used
      in a bioassay (Mennear, J.H., McConnell, E.E., Huff, J.E., Renne, R.A., and
      Giddens, E. (1988). Ann. NY Acad. Sci. 534, 343-351). The tumor incidence data in
      mice were fitted to the DPX yields and to the airborne concentration of DCM as
      alternative measures of exposure using the linearized multistage (LMS) model. The
      two dose measures yielded similar maximum likelihood estimates for the cancer
      risk at concentrations from 10 to 100 ppm, but the upper 95% confidence limit on
      the risk was reduced by two orders of magnitude when DPX rather than the airborne
      concentration was used as the measure of exposure. The results demonstrate that
      an internal dosimeter such as DPX can markedly improve the precision of low-dose
      risk estimates, while having only a minor effect on the maximum likelihood
      estimates calculated with the LMS model.

PMID- 8998947
TI  - Evaluation of the developmental toxicity of dermally applied monoethanolamine in
      rats and rabbits.
AB  - Pregnant Sprague-Dawley rats and New Zealand White rabbits were exposed dermally
      to 0, 10, 25, and 75 mg/kg/day of monoethanolamine (MEA) for approximately 6
      hr/day on Days 6 through 15 (rats) or 6 through 18 (rabbits) of gestation. A
      fifth dose group of 225 mg MEA/kg/day was evaluated in rats only. Dermal exposure
      of pregnant rats to 225 mg/kg/day and rabbits to 75 mg/kg/day resulted in
      significant increases in the incidence of skin irritation/lesions and maternal
      body weight effects. In general, the dermal irritation observed at the high dose
      was progressive, beginning with erythema and leading to necrosis, scabs, and scar
      formation. Doses of 25 mg/kg/day to rabbits produced only minor irritation.
      Despite maternal effects observed in rats and rabbits, no evidence of
      developmental or fetal toxicity was observed at any dose level tested. Thus, it
      was concluded that MEA was not developmentally toxic following dermal application
      at exposure levels up to and including 225 mg/kg/day for rats and 75 mg/kg/day
      for rabbits.

PMID- 8998948
TI  - Two-dimensional electrophoretic analysis of compartment-specific hepatic protein
      charge modification induced by thioacetamide exposure in rats.
AB  - Thioacetamide (TA) is a well-known hepatotoxicant. It has been reported that an
      obligate intermediate of TA binds to proteins with the formation of
      acetylimidolysine derivatives that are responsible for TA-induced hepatotoxic
      effects. TA has also been reported to cause chemically induced cell death via
      both apoptosis and necrosis. The objective of this study was 2-fold: first, to
      investigate the effect of TA exposure on protein charge modifications in the rat
      liver and second, to study the role of these molecular correlates in the
      regulation of cell death. Male Sprague-Dawley rats (200-225 g, 7-8 weeks old)
      were divided into four major groups and treated intraperitoneally with a 12-fold
      dose range of TA (50, 150, 300, and 600 mg TA/kg) dissolved in water. Using whole
      liver extracts, alterations in the hepatic protein pattern following treatment
      with the 12-fold dose range of TA were studied using high-resolution, two
      dimensional polyacrylamide gel electrophoresis and computerized image analysis.
      The results indicate that charge modification was clearly evident as early as 2
      hr with the lowest dose of 50 mg TA/kg. At this dose and time endoplasmic
      reticulum proteins, calreticulin, grp78, and ER6O exhibited acidic charge
      variants. The effect of TA became more prominent with dose and time. Generally
      the elevation of charge modification indices (CMI) by TA appeared to reach a peak
      between 4 and 6 hr and then while CMI either leveled off or declined in the lower
      two doses of 50 and 150 mg TA/kg, it continued to remain elevated with the higher
      doses of 300 and 600 mg TA/kg. This dichotomy in the elevation of CMI is in close
      correspondence to the pattern of cell death observed with a similar dose range of
      TA, where lower doses (50 and 150 mg TA/kg) predominantly cause cell death via
      apoptosis while higher doses cause cell death via necrosis. Delayed charge
      modification was observed with the cytosolic hsc70s with the 300 and 600 mg TA/kg
      treatments, indicating that the reactive metabolite(s) slowly leak out into the
      cytosol from the endoplasmic reticulum. There were no alterations in the
      mitochondrial proteins hsp60 and grp75, suggesting that TA has no effect on the
      mitochondrion, its effects primarily being confined to the endoplasmic reticulum.
      The concept of looking at these proteins as biomarkers of tissue injury has
      validity. These changes may be indicators of bioactivation and adduct formation
      and also may be signaling events in the regulation of the mode of cell death.

PMID- 8998949
TI  - Effect of antioxidants, anti-inflammatory drugs, and histamine antagonists on
      sparfloxacin-induced phototoxicity in mice.
AB  - We examined the effects of antioxidants, anti-inflammatory drugs, and histamine
      antagonists on auricular inflammation and retinal degeneration induced by the
      phototoxicity of sparfloxacin (SPFX), a quinolone antibacterial agent. Catalase
      (CAT), dimethyl sulfoxide (DMS0), dexamethasone (DM), indomethacin (IM),
      phenidone (PD), AA-861 (AA), pyrilamine maleate (PY), or cimetidine (CM) was
      continuously administered to female Balb/c mice using microosmotic pumps for 72
      hr and intraperitoneally once before SPFX administration. The mice were given a
      single oral administration of 50 or 100 mg/kg SPFX and irradiated with
      ultraviolet-A (UVA) light at 1.5 mW/cm(2) for 4 hr. SPFX administration plus UVA
      irradiation induced thickening and inflammation of the auricular skin and retinal
      degeneration in the eye. CAT and DMS0 significantly inhibited the auricular
      thickening only 4 hr after SPFX administration. DM, IM, and PD also inhibited
      this toxicity from 4 to 48 or 72 hr. On the other hand, PY and CM showed no
      effect on this change. With regard to the eye, CAT and DMSO completely inhibited
      the occurrence of retinal degeneration and IM and PD tended to decrease its
      incidence, whereas DM, AA, PY, and CM showed no or an exacerbating effect. These
      results suggest that reactive oxygen species contribute to the initiation of
      auricular inflammation and retinal degeneration and that cyclooxygenase products
      are also involved in the initiation and later progression of auricular
      inflammation. They also show that histamine and 5-lipoxygenase products are not
      involved in either phototoxic lesion.

PMID- 8998950
TI  - Incorporating Monte Carlo simulation into physiologically based pharmacokinetic
      models using advanced continuous simulation language (ACSL): a computational
      method.
AB  - Biologically based models with physiological parameters are becoming more popular
      as a tool to estimate target tissue doses from chemical exposures. However, the
      majority of current physiologically based pharmacokinetic (PBPK) models do not
      take into account the uncertainty and/or variability within the various model
      parameters. Consideration of uncertainty is important to evaluate the predictive
      ability and complexity of a model as well as identification of parameters which
      contribute disproportionately to variability in model output. In order to
      estimate the uncertainty in PBPK model output, a versatile and simple
      computational method is presented which can be readily incorporated into the
      majority of PBPK models without extensive additions to model computer code. In
      this paper, a separate computer program for Monte Carlo simulation is furnished
      that randomly samples values for model parameters and writes them into a run-time
      language (command file) format which can then be utilized to execute individual
      PBPK models. Modifications to the PBPK model allow the desired output to be
      written to a data file for statistical analysis. The method presented in this
      paper is applied to a simple PBPK model for benzene disposition.

PMID- 8998951
TI  - Oncogenicity testing of 2-ethylhexanol in Fischer 344 rats and B6C3F1 mice.
AB  - 2-Ethylhexanol (2EH) is a weak nongenotoxic hepatic peroxisome proliferator in
      the rat. It is a high-volume chemical intermediate in the preparation of the
      plasticizers bis-(2-ethylhexyl) adipate (DEHA), bis-(2-ethylhexyl) phthalate
      (DEHP), and tris-(2-ethylhexyl) phosphate (TEHP), which are weak hepatocellular
      tumorigens in female mice. In consequence, the oncogenic potential of 2EH was
      evaluated in male (M) and female (F) rats and mice (50 animals/sex/group). Oral
      gavage doses of 2EH in 0.005% aqueous Cremophor EL (polyoxyl-35 castor oil) were
      given five times a week to rats: 0 (water), 0 (vehicle), 50, 150, and 500 mg/kg
      for 24 months, and to mice: 0 (water), 0 (vehicle), 50, 200, and 750 mg/kg for 18
      months. Statistical comparisons of data were made between vehicle controls and
      treatment groups. There were no differences of biological significance between
      data from vehicle and water control groups. In rats, there were no dose-related
      changes at 50 mg/kg. There was reduced body weight gain at 150 mg/kg (M, 16; F,
      12%) and 500 mg/kg (M, 33; F, 31%) and an increased incidence of lethargy and
      unkemptness. There were dose-related increases in relative liver, stomach, brain,
      kidney, and testis weights at sacrifice. Female rat mortality was markedly
      increased at 500 mg/kg. There was marked aspiration-induced bronchopneumonia in
      rats at 500 mg/kg; hematologic, gross, and microscopic changes, including tumors,
      were otherwise comparable among all rat groups. In mice at 50 and 200 mg/kg there
      were no dose-related changes and essentially no time-dependent or time
      independent adverse trends in liver tumor incidence at the 5% significance level.
      At 750 mg/kg mouse body weight gain was reduced (M, 26; F, 24%), and mortality
      increased (M and F, 30%) versus vehicle controls. At 750 mg/kg there was a slight
      increase in nonneoplastic focal hyperplasia in the forestomach of mice (M 5/50, F
      4/50) versus vehicle controls (M 1/50, F 1/50). There were increases in mouse
      relative liver (F, 21%) and stomach (M, 13%; F, 19%) weights at 750 mg/kg. There
      was a 12% incidence of hepatic basophilic foci and an 18% incidence of
      hepatocellular carcinomas in male mice at 750 mg/kg, not statistically
      significant compared with either control by Fisher's exact test. There was a 12%
      incidence of hepatic basophilic foci and a 10% incidence of hepatocellular
      carcinomas in female mice at 750 mg/kg, statistically significant (p < 0.05)
      compared with vehicle but not with water controls by Fisher's exact test. There
      were no metastases. Time-dependent and -independent statistical analyses showed
      an adverse trend in the incidence of hepatocellular carcinomas in male and female
      mice, correlated with toxicity (expressed as mortality) at 750 mg/kg. The time
      adjusted incidence of hepatocellular carcinomas in male mice (18.8%) was within
      the historical normal range at the testing facility (0-22%), but that in females
      (13.1%) lay outside the normal range (0-2%). Under the conditions of these
      studies 2EH was not oncogenic in rats, but there were weak adverse trends in
      hepatocellular carcinoma incidence in mice at high dose levels which may have
      been associated with toxicity. The major effects of chronic dosing were mortality
      in female rats at 500 mg/kg and in male and female mice at 750 mg/kg, accompanied
      by reductions in body weight gain in rats at 150 and 500 mg/kg and in mice at 750
      mg/kg. Direct comparison of any tumorogenic effects of 2EH given alone to female
      mice with those due to 2EH formed in vivo from DEHA, DEHP, or TEHP is limited by
      the high mortality caused by 2ER in female mice at equivalent doses of 2EH. While
      2EH may be a contributing factor in the hepatocellular carcinogenesis in female
      mice associated with the chronic administration of DEHA and DEHP, it is unlikely
      to be the entire proximate carcinogen.

PMID- 8998952
TI  - Prevalence of endometriosis in rhesus (Macaca mulatta) monkeys ingesting PCB
      (Aroclor 1254): review and evaluation.
AB  - A total of 80 menstruating rhesus monkeys (Macaca mulatta) were equally and
      randomly divided among groups receiving 0, 5, 20, 40, or 80 mu g of Aroclor
      1254/kg body weight/day during a 6-year toxicological-reproduction study. During
      the first 3 years of the study, 4 of the treated monkeys became moribund and were
      euthanized; 3 had endometriosis. This finding suggested a possible link between
      the PCB treatment and the occurrence of endometriosis. However, neither a
      laparoscopic examination of the control and high-dose monkeys nor the necropsy
      data provided evidence for a possible link between the PCB treatment and the
      observed incidence (37% (6/16) of controls; 25% (16/64) of treated monkeys and/or
      the severity of the endometrial lesions. Additional clinical and historical data
      not contained in previous reports are presented to facilitate independent
      evaluation of the relationship between PCB ingestion and endometriosis. We
      conclude that the incidence and severity of the endometriosis lesions observed in
      the rhesus monkeys utilized in this study did not have any relationship with the
      dosages of Aroclor 1254 they ingested.

PMID- 8998953
TI  - Adaptation to ozone in rats and its association with ascorbic acid in the lung.
AB  - Ozone (O3) adaptation is a well-known, but poorly understood phenomenon that has
      been demonstrated in humans and laboratory animals. This study examined pulmonary
      function and bronchoalveolar lavage fluid (BALF) parameters in O3-adapted F-344
      rats to explore possible mechanisms of adaptation. Of particular interest was
      ascorbic acid (AA), an antioxidant reported to be protective against O3 injury
      and found to be increased in O3-adapted rats. Adaptation was induced by exposure
      to 0.25 ppm O3, 12 hr/day for 6 or 14 weeks and evaluated with a challenge test,
      one that reexposed rats to 1.0 ppm O3 and measured attenuation in the O3 effect
      on frequency of breathing. Pulmonary function was assessed 1 day postexposure and
      adaptation and BALF were evaluated 1, 3, and 7 days postexposure. Results showed
      that forced vital capacity increased over time but decreased due to exposure and
      that the 14-week, O3-exposed rats had an increase in forced expiratory flow rate.
      All of the O3-exposed rats that were tested demonstrated adaptation on
      Postexposure Days 1, 3, and 7, but it was diminished on Day 7. Adaptation was
      also more pronounced in rats exposed for 14 weeks. Except for AA, BALF levels of
      total protein, potassium, lysozyme, uric acid, and alpha-tocopherol were
      unaffected by O3 exposure. Lactic acid dehydrogenase, alkaline phosphatase,
      glucose-6-phosphate dehydrogenase, and total glutathione were also assayed but
      were always below detectable limits. Ascorbic acid concentrations were elevated
      on Days 1, 3, and 7, showing postexposure patterns similar to those found for
      adaptation. Significant correlation was found between AA concentration and the
      magnitude of adaptation (r = 0.91, p < 0.002). We conclude that AA may play an
      important role in mechanisms associated with O3 adaptation in rats.

PMID- 8998954
TI  - Increased immune and inflammatory responses to dust mite antigen in rats exposed
      to 5 ppm NO2.
AB  - Immune hypersensitivity to house dust mite antigen (HDM) is a frequent cause of
      respiratory allergy. The objective of this study was to determine whether
      exposure to NO2, a common indoor air pollutant, modulates immune responses to HDM
      and influences immune-mediated lung disease. Brown Norway rats were immunized ip
      with 100 micrograms semipurified antigen and Bordetella pertussis adjuvant and
      challenged 2 weeks later with an intratracheal injection of 50 micrograms of a
      crude antigen preparation. Exposure to 5 ppm NO2 for 3 hr after both immunization
      and challenge procedures resulted in significantly higher levels of antigen
      specific serum IgE, local IgA, IgG, and IgE antibody than air controls, and
      increased numbers of inflammatory cells in the lungs. Lymphocyte responsiveness
      to antigen in the spleen and MLN was also significantly higher in NO2-exposed
      animals. These data show that exposure to a common air pollutant can upregulate
      specific immune responses and subsequent immune-mediated pulmonary inflammation.

PMID- 8998956
TI  - Lipid peroxidation and formation of 8-hydroxydeoxyguanosine from acute doses of
      halogenated acetic acids.
AB  - Chlorinated, brominated, and mixed bromochloro acetates are major by-products of
      water disinfection by chlorine or ozone. The chlorinated acetates,
      trichloroacetate (TCA) and dichioroacetate (DCA), are carcinogenic in rodents.
      Brominated analogs of TCA and DCA have received little study. TCA and DCA induce
      lipid peroxidation in the livers of rodents when administered acutely. Oxidative
      stress can also result in oxidative damage to DNA, most commonly measured as
      increases in 8-hydroxydeoxyguanosine (8-OHdG) adducts. In this study, the ability
      of acute doses of TCA, DCA, dibromoacetate (DBA), bromodichloroacetate (BDCA),
      and bromochloroacetate (BCA) to induce lipid peroxidation and 8-OHdG formation
      was examined. Male B6C3F1 mice developed significant increases in 8-OHdG/dG
      ratios in nuclear DNA isolated from livers when treated with haloacetates. The
      extent of 8-OHdG formation appeared to be related to the ability to induce
      thiobarbituric acid-reactive substances (TBARS). The order of potency was DBA =
      BCA > BDCA > DCA > TCA. The induction of 8-OHdG was found to be generally more
      sensitive to treatment with haloacetates than the TBARS response. Significantly
      elevated levels of 8-OHdG were observed at doses of DBA, BCA, and BDCA as low as
      30 mg/kg. We suggest that formation of 8-OHdG by brominated haloacetates may
      contribute to their toxicological effects.

PMID- 8998955
TI  - An analysis of nasal irritation thresholds using a new solvation equation.
AB  - In the present paper we have developed a quantitative structure-activity
      relationship (QSAR) equation for nasal pungency caused by nonreactive volatile
      organic compounds (VOCs). Our QSAR was developed upon previously published nasal
      pungency thresholds in anosmics, i.e., patients lacking a sense of smell and thus
      responding only to sensory irritation evoked by trigeminal nerve stimulation. The
      reported solvation equation, which fits the data with considerable precision,
      describes sensory potency in terms of interaction via electron pairs,
      dipolarity/polarizability, hydrogen bond acidity and basicity, and
      hydrophobicity. It correspondingly suggests relevant physicochemical properties
      of the biophase where the sensory response is brought about. The equation implies
      that in the range of molecular size where nonreactive VOCs can produce any
      pungency, transport from the air to the biophase strictly determines potency. In
      this respect, the potency of nasal pungency shares characteristics with the
      ability of VOCs to cause narcosis and anesthesia.

PMID- 8998957
TI  - A generic toxicokinetic model for persistent lipophilic compounds in humans: an
      application to TCDD.
AB  - This paper discusses a toxicokinetic model describing the distribution of TCDD in
      the human body during a lifetime. The model divides the body into several
      physiological compartments, their weights being functions of age. Ingested TCDD
      is instantaneously distributed over all compartments according to their lipid
      content. The liver eliminates TCDD from the body by a first-order process. Intake
      depends on age, as estimated from food consumption survey data combined with data
      on TCDD concentrations in various foods. It is shown that historical changes in
      intake, due to changes in environmental concentrations and in dietary habits,
      should be taken into account as well. Elimination rate and bioavailability, the
      only unknown parameters in the model, were estimated by calibrating the model to
      human data on internal concentrations. The generic formulation of the model makes
      it suitable for slowly eliminated lipophilic compounds in general.

PMID- 8998958
TI  - Development of an in vitro method for skin corrosion testing.
AB  - National and international regulations require that chemicals must be properly
      classified, labeled, packaged, and transported based on their ability to damage
      or destroy tissue, e.g., skin. Traditionally, skin corrosion assessments were
      based on tests involving topical application of test substances to the skin of
      rabbits. In the present work, an in vitro skin corrosion test based on the use of
      reconstructed human skin cultures was developed as a potential replacement for in
      vivo rabbit skin tests for corrosion. In the in vitro method, test substances
      were applied topically to the stratum corneum surface of human skin cultures.
      Skin culture damage or cytotoxicity was measured as decreased 3-[4,5
      dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide (MTT) vital dye metabolism.
      In time-course experiments, the time (in minutes) of test material exposure
      eliciting a 50% reduction of MTT metabolism (i.e., t50 value) was calculated.
      Using this method we evaluated 24 chemicals and found that the 9 corrosive
      chemicals were accurately distinguished from 15 strong, moderate, or mild skin
      irritants, using an in vitro cutoff of t50 < 3 min. Histologic examination of the
      cultures indicated gradations of epidermal necrosis quantitated using a specially
      designed grading scale, which correlated well with the corrosivity of treatment
      chemicals and cytotoxicity measurements. The predictivity of the method was
      confirmed and was consistent in skin culture models from two suppliers. Thus, the
      utility of human skin equivalent cultures as a screening tool for prediction of
      skin corrosivity appears to be independent of the commercial source of the
      cultures. We conclude that the in vitro assay using human skin equivalent
      cultures is a promising alternative to in vivo rabbit skin corrosion tests for
      assessment of the corrosivity of chemicals to human skin.

PMID- 8998960
TI  - Molecular evolution of fish neurohypophysial hormones: neutral and selective
      evolutionary mechanisms.
AB  - Chemical identification of neurohypophysial hormones from about 80 vertebrate
      species reveals that two evolutionary lineages can be traced in bony vertebrates,
      a vasopressin-like hormone line and an oxytocin-like hormone line, which were
      derived from the duplication of an ancestral gene that may have been present in
      agnathans. All of the 13 neurohypophysial hormones are built in the same
      structural pattern, namely, a nonapeptide with a disulfide bridge linking half
      cystines in positions 1 and 6. There is a striking evolutionary stability in bony
      vertebrates since virtually all species belonging to a given class are endowed
      with the same peptides. In contrast, in cartilaginous fishes, the oxytocin-like
      hormone displays a great diversity. Six distinct peptides are characterized in
      this group. The proposed hypothesis is that the stability in primary structure in
      bony vertebrates is due to selective pressure. This selective pressure is
      associated with an ion-based osmoregulation, whereas in Chondrichthyes the
      occurrence of an urea-based osmoregulation has relieved the hormones from the
      control of ionic homeostasis. Variations in primary structures in cartilaginous
      fishes are regarded as relevant to the neutral evolution as defined by Kimura.
      According to this concept, oxytocin of placental mammals results from selective
      evolution, whereas the same molecule found in ratfish proceeds from random
      genetic drift.

PMID- 8998959
TI  - Catalytic and immunochemical characterization of cytochrome P450 isozyme
      induction in dog liver.
AB  - The purpose of this study was to characterize hepatic cytochrome P450 induction
      in the dog by phenobarbital, beta-naphthoflavone, dexamethasone, and isoniazid
      using catalytic activities and Western blots with antibodies prepared against rat
      cytochrome P450 isozymes. Male beagle dogs were treated with phenobarbital (10
      mg/kg for 2 days and 30 mg/kg for the following 5 days), beta-naphthoflavone (50
      mg/kg for 5 days), or isoniazid (10 mg/kg for 2 days and 30 mg/kg for the
      following 5 days). Female beagle dogs were treated with dexamethasone (50 mg/kg
      for 5 days). Increases in the liver/body weight ratio were observed after
      treatment of dogs with phenobarbital (133% of control) and dexamethasone (153%).
      Total cytochrome P450 content was increased as a percentage of control after
      treatment with phenobarbital (264%) and (3-naphthoflavone (186%), while it
      slightly decreased after treatment with isoniazid (54%) and dexamethasone (71%).
      Dog liver microsomes hydroxylated testosterone mainly at the 6-beta and 16-alpha
      positions but also at the 6-alpha-, 15-beta-, 15-alpha-, 16-beta-, 18-, 2-beta-,
      and 17-positions. There were no sex differences in terms of regio-selectivity of
      testosterone metabolism between control male and female dogs. Treatment of dogs
      with phenobarbital produced increases in 6-beta- (184%), 16-alpha- (379%), 16
      beta- (210%), 18- (195%), and 2-beta-testosterone (203%) hydroxylase and
      pentoxyresorufin 0-dealkylase (651%) activities. On Western blots, phenobarbital
      treatment produced induction of P450 3A- and 2B1-related proteins. Although
      treatment with dexamethasone resulted in a large increase in liver weight, no
      significant increase in P450 3A-related protein or 6-beta-hydroxylase activity
      was detected. However, dexamethasone and isoniazid treatment produced slight
      increases in chlorzoxazone hydroxylase activity. Treatment with isoniazid induced
      a P450 2E1-related protein. Treatment with (beta-naphthoflavone produced
      increases that were 689 and 357% of control in ethoxyresorufin 0-deethylase and
      chlorzoxazone hydroxylase activities, respectively. Beta-Naphthoflavone treatment
      increased the amount of two proteins immunochemically related to the cytochrome
      P450 1A subfamily. Thus, although generally similar to other species, the
      response of the dog to cytochrome P450 inducers differs significantly from the
      rat and human in some cases.

PMID- 8998961
TI  - Heterologous expression of the spiny dogfish shark (Squalus acanthias) cytochrome
      P450c17 (17 alpha-hydroxylase) in Escherichia coli.
AB  - Cytochrome P450c17 is a key steroidogenic enzyme for the production of sex
      steroids in gonadal tissue and for cortisol production in adrenal tissue. This
      protein possesses two enzymatic activities. The 17-alpha-hydroxylase activity
      introduces a hydroxyl group into the steroid nucleus. The resultant 17-alpha
      hydroxylated, C(21) pregnenes can be converted to a C(19) androgen by the
      C(17,20)-lyase activity. The cDNA encoding the spiny dogfish shark (Squalus
      acanthias) testicular form of cytochrome P450c17 was used to direct heterologous
      expression in Escherichia coli. The wild-type P450c17 protein was not conducive
      to expression in E. coli using either a pET21 or a pCwori+ vector. However,
      modification of the amino terminus permitted overexpression of inactive shark
      protein with the pFT21 vector. This protein was fused with a hexahistidinyl
      peptide to facilitate purification by column chromatography using a Ni(2+)
      chelated resin. Transformed bacteria yielded an average of 1.8 mg of purified,
      concentrated P450c17 protein per 100-ml culture. This modified protein was used
      to raise antisera in rabbits and the resultant antisera was used at a working
      titer of 1:10,000 for Western blot analysis. Culture conditions that result in
      the accumulation of bioactive recombinant bovine P450c17 failed to demonstrate
      expression of either the native or the modified form of shark P450c17 using the
      pCWori+ and pET21 vectors. These results suggest that the amino terminus of the
      native shark P450c17 was not conducive to synthesis in E. coli. However,
      modifications of the amino terminus permitted synthesis of an inactive protein
      that was protected from degradation within inclusion bodies.

PMID- 8998962
TI  - Atrial and ventricular natriuretic peptide concentrations in plasma of freshwater
      and seawater-adapted eels.
AB  - Plasma levels of atrial and ventricular natriuretic peptide (ANP and VNP) were
      measured in freshwater (FW)- and seawater (SW)-adapted eels using homologous
      radioimmunoassays. Anesthesia with tricaine (MS222) and exposure of the
      pericardium for blood sampling from the ventral aorta affected plasma ANP and VNP
      levels. ANP and VNP levels in the ventral aorta were higher than those in the
      dorsal aorta when blood was collected simultaneously from both aortae of
      cannulated conscious FW eels, perhaps reflecting branchial extraction of the
      peptides. This phenomenon was not observed in SW eels. Based on these results,
      blood was sampled from conscious eels through a catheter implanted in the ventral
      aorta because it appears to reflect most accurately ANP secretion. Plasma ANP and
      VNP levels measured in more than 100 conscious FW and SW eels displayed large
      variations at each month despite acclimation to laboratory conditions at 180 for
      more than 1 week in FW eels or for more than 2 weeks in SW eels. However,
      concentrations of ANP and VNP averaged from all data were not different between
      FW and SW eels: 68.1 +/- 2.9 (FW: n = 155) vs 60.7 +/- 3.6 (SW: n = 104) for ANP,
      51.6 +/- 3.0 (FW: n = 69) vs 55.0 +/- 3.7 (SW: n = 54) for VNP (fmol/ml in each
      case). Plasma Na concentration and osmolality were significantly higher in SW
      eels than in FW eels. Plasma ANP and VNP levels thus do not seem to be affected
      by chronic changes in plasma Na concentration and osmolality.

PMID- 8998963
TI  - Involvement of endogenous prolactin in the expression of courtship behavior in
      the newt, Cynops pyrrhogaster.
AB  - In order to ascertain the involvement of endogenous prolactin (PRL) in the
      expression of courtship behavior by the male newt, Cynops pyrrhogaster, antiserum
      against homologous PRL was administered to male newts, which had been exhibiting
      courtship behavior in the field and had been taken to the laboratory. The effect
      of the antiserum on the preference of terrestrial over aquatic habitats also was
      investigated. Within 24 hr of the first injection of antiserum, both incidence
      and frequency of courtship behavior declined markedly compared with those in the
      preimmune serum-injected newts. The anti-PRL serum-induced decline became more
      conspicuous thereafter. These animals came to prefer a terrestrial habitat.
      Cessation of antiserum injection and administration of PRL restored the
      expression of courtship behavior to a certain extent and altered their habitat
      preference from terrestrial to aquatic. The results strongly suggest the
      involvement of endogenous PRL in the expression of courtship behavior as well as
      in the preference of aquatic habitat.

PMID- 8998964
TI  - In vivo steroid metabolism in embryonic and newly hatched steelhead trout
      (Oncorhynchus mykiss).
AB  - Radioactive pregnenolone (P5), testosterone (T), or 17-beta-estradiol (E2) was
      microinjected into steelhead trout, Oncorhynchus mykiss, embryos and newly
      hatched yolk-sac fry (alevins) to detect in vivo metabolism. We also assayed the
      water used to incubate animals for 10 hr after microinjection to detect possible
      metabolite excretion. High pressure liquid chromatography and thin layer
      chromatography were used to separate and tentatively identify steroid
      metabolites. Metabolites of P5 were androstenedione (AN), E2, T, and glucuronides
      of E2 and T in embryos and AN, E2, progesterone, 17-alpha, 20-beta
      dihydroxyprogesterone, and P5 glucuronide in alevins. E2 and its glucuronide were
      synthesized from precursor T in the embryos and alevins; however, the amounts of
      E2 and E2 glucuronide synthesized in the embryos were 10 and 3 magnitudes greater
      than those detected in alevins. Testosterone glucuronide was synthesized in
      similar amounts in both stages of development. Embryos did not synthesize free
      metabolites from E2 precursor, but E2 glucuronide was detected from E2 precursor.
      Estradiol in alevins was metabolized into unidentified free and glucuronide
      conjugated steroids. Three unknown metabolites synthesized from P5 precursors and
      seven unknown substances produced in animals injected with testosterone or
      estradiol precursors were detected. Free metabolites were detected in the
      incubation water that held the animals (embryos and alevins) for 10 hr after
      microinjection with T or E2. Glucuronide metabolites were not excreted by embryos
      into the incubation water 10 hr after microinjections with any of the steroid
      precursors; however, alevins excreted glucuronides into the incubation water when
      supplied with precursor T. These results imply that endogenous steroid metabolism
      of maternally contributed steroids is active during early development.

PMID- 8998965
TI  - Growth hormone-releasing hormone immunoreactivity in the brain, pituitary, and
      pineal of the goldfish, Carassius auratus.
AB  - Using antisera directed against carp growth hormone-releasing hormone (cGHRH),
      the distribution of immunoreactive (ir) structures in the brain, pituitary, and
      pineal of the goldfish, Carassius auratus, was investigated. The antisera were
      produced in rabbits by administration of cGHRH(1-44)-NH(2) followed by cGHRH(1
      45)-OH for different periods of time, both coupled to human alpha-globulins via
      bisdiazotized benzidine as immunogen. Immunoreactive perikarya were visualized in
      the nucleus preopticus periventricularis (NPP), nucleus lateralis tuberis (NLT),
      nucleus of the lateral lemniscus (NLL), and the pineal. The preoptic area and
      area ventralis telencephali seemed to receive innervation from the NPP cells. The
      fibers of the NLT cell bodies extended caudally along the infundibular floor and
      innervated the hypophysis. The processes of the NLL perikarya extended rostrally
      along the lateral lemniscus, curved ventrally along the outer margin of the
      glomerular nuclear complex, and extended to the dorsal area of the lateral
      recess, while issuing fascicles that branched off and fanned out to innervate
      extensively the nucleus diffusus of the hypothalamic inferior lobes and the
      nucleus lateralis tori; several fiber bundles branched off and extended toward
      the lateral areas of the paraventricular organ area and even into the rostral
      region of the hypothalamic inferior lobes. A small percentage of the
      corticotrophs of the rostral pars distalis, a few cells in the central area of
      the pars intermedia (PI), and neurohypophysial fibers in the peripheral area of
      the PI of the pituitary gland had colocalization of GHRH-ir; GHRH-ir fibers in
      the rostral and proximal pars distalis were sparse. It is suggested that the GHRH
      ir perikarya of the diencephalon may stimulate growth hormone release either by
      modulating the activity of somatotrophs or of other hypothalamic neurosecretory
      neurons. The innervation of the hypothalamic inferior lobe by GHRH-ir perikarya
      of the NLL suggests some influence on feeding processes. Presence of GHRH in the
      pineal implies involvement in some daily cyclic activity.

PMID- 8998966
TI  - Changes in bioactive prolactin-like activity in plasma and its relationship to
      incubation behavior in breeding ring doves.
AB  - Previous radioimmunoassay (RIA) data indicate that plasma prolactin (PRL) is
      elevated during the late incubation and the early posthatching periods of the
      ring dove breeding cycle. Although these changes are temporally associated with
      changes in PRL-dependent crop sac growth, the precise relationship between
      immunoreactive and bioactive PRL has not been directly examined. To investigate
      this question and to further explore the relationship between sitting behavior
      and PRL secretion, we used rat Nb2 lymphoma cell proliferation to estimate the
      concentration of bioactive PRL-like activity (PLA) in the plasma of breeding ring
      doves. Serial dilutions of dove pituitary homogenate and dove plasma stimulated
      mitogenic responses that were parallel to those observed with purified ovine PRL.
      Changes in plasma PLA during the breeding cycle closely resembled changes in PRL
      that have been previously reported by RIA, although the relative changes in PLA
      were more pronounced. In both sexes, PLA remained at basal levels prior to egg
      laying and during early incubation (Day 4-5) but then abruptly increased to reach
      peak values near the time of hatching (Day 14-15). Activity remained high for 3-4
      days after hatching, declined gradually thereafter, and returned to baseline
      values by Posthatching Days 14-17. Plasma PLA levels of birds sampled at the end
      of incubation were correlated with those of their breeding partners. In the
      majority of pairs, females had higher PLA levels than their mates at this stage
      even though no significant overall sex differences in PLA levels were observed.
      Plasma PLA declined precipitously in birds that were nest deprived on the last
      day of the incubation period. Nevertheless, plasma PLA levels of normally
      breeding birds at the end of incubation were not correlated with the average time
      spent in the nest during the incubation period. However, day-to-day variability
      in time spent in the nest correlated negatively with plasma PLA in incubating
      males, and females exhibited a similar trend that approached significance. These
      data suggest (1) that published RIA estimates of PRL are reasonably accurate
      reflections of changes in bioactive PLA in dove plasma and (2) that while sitting
      duration itself is not strongly related to plasma PLA, large day-to-day
      fluctuations in nest occupation time are associated with reduced PLA levels in
      incubating doves.

PMID- 8998967
TI  - Expression of P450(17 alpha) hydroxylase and P450 aromatase genes in the chicken
      gonad before and after sexual differentiation.
AB  - The onset and localization of P450(17-alpha)-hydroxylase (P450(17-alpha)) and
      P450 aromatase (P450arom) mRNA expression were studied in the gonads of chicken
      embryos at Days 4-9 of incubation by in situ hybridization analysis, and
      expression of both mRNAs was measured in the ovary and testis of the chicken
      after sexual differentiation by Northern and slot-blot analysis and was related
      to changes in concentration of 17-beta-estradiol (E2) in the gonad. In situ
      hybridization analysis showed the first detection of P450(17-alpha) mRNA at Days
      5-6 of incubation in the genetic male and female gonads and the first detection
      of P450arom at Day 6.5 of incubation in the female gonad but none was detected in
      the male gonad. Both mRNAs were observed in the medullary cords of the gonad.
      Slot-blot analysis demonstrated that levels of P450(17-alpha) mRNA in the ovary
      remained high during the period between Day 10 of incubation and 7 days of
      posthatching, while those in the testis remained low at Days 10-14 of incubation
      but increased at Day 16 of incubation up to posthatching days. Levels of P450arom
      mRNA in the left ovary were invariably higher than those of the right ovary and
      testis throughout the period between Day 10 of incubation and 7 days of
      posthatching. These results suggest that expression of P450arom mRNA occurring in
      the genetic female gonad around Day 6 is associated, at least in a part, with
      sexual differentiation toward femaleness by increasing E2 production which may
      promote cellular proliferation of the left gonad. In contrast, in the genetic
      male gonad marked expression of P450(17-alpha) mRNA with little expression of
      P450arom mRNA may lead to production of androgen which promotes the gonadal
      development to the testis.

PMID- 8998968
TI  - Effects of aromatase inhibitor on sex differentiation and levels of P450 (17
      alpha) and P450 arom messenger ribonucleic acid of gonads in chicken embryos.
AB  - On Day 5 of incubation fertilized eggs of single-comb White Leghorn hens were
      injected with an aromatase inhibitor (AI) and the sex reversal effect and levels
      of mRNA of P450(17alpha-hydroxylase) (P450(17alpha)) and 450(aromatase)
      (P450(arom)) were evaluated by observation of gonadal phenotype and by Northern
      and slot blot analysis. Individual genetic sex was evaluated by Southern blot
      analysis of red blood cells using a female sex chromosomal W-specific DNA probe.
      Saline injection had no sex reversal effect, whereas AI injection resulted in 50%
      sex reversal from genetic female but no effect on male. Levels of P450(17-alpha)
      mRNA were high in both ovary and testis in the control group but these levels
      were lowered significantly in ovary, testis, and sex-reversed gonad (testis) in
      the AI-treated group. On the other hand, levels of P450(arom) mRNA in the ovary
      were higher than those in the testis of the control group. AI treatment
      significantly suppressed ovarian levels of P450(arom) mRNA. Although estradiol
      alone failed to prevent the phenotypic male to female change, coadministration of
      estrogen suppressed the sex-reversal effect of AI and restored mRNA levels of
      P450(arom) in the ovary to control levels. These results suggest that expression
      of P450(arom) mRNA and estrogen plays an important role in sex differentiation of
      the female gonad of the chicken.

PMID- 8998969
TI  - Bombyx and Manduca prothoracicotropic hormones: an immunologic test for
      relatedness.
AB  - Prothoracicotropic hormone (PTTH) controls the synthesis of ecdysteroids (molting
      hormones) by the insect prothoracic gland and thereby plays a critical role in
      insect growth, molting, and metamorphosis. PTTH has been purified, and cDNA
      clones obtained, from only one insect, the silkmoth Bombyx mon. Recently, a
      partial amino acid sequence was obtained for-a putative PTTH from the tobacco
      hornworm, Manduca sexta, and the data suggested an unexpected homology to a
      vertebrate retinoid binding protein rather than to the Bombyx PTTH. In this
      study, a monoclonal antibody against the Bombyx PTTH was added to in vitro assays
      that assess the ability of partially purified Manduca PTTH to stimulate
      prothoracic gland ecdysteroid and protein synthesis. The results indicate that
      Bombyx and Manduca PTTHs are indeed members of the same protein family that have
      likely diverged in the PTTH receptor-binding region.

PMID- 8998970
TI  - Excretory fate of estradiol and progesterone in the African elephant (Loxodonta
      africana) and patterns of fecal steroid concentrations throughout the estrous
      cycle.
AB  - We developed and validated a noninvasive method to quantify fecal estrogens and
      progestins as a tool for monitoring long-term ovarian activity in free-ranging
      African elephants. The lag times between iv injection of [(3)H]estradiol and
      [(14)C]progesterone and peak excretion of radioactivity in urine and feces were
      approximately 4 hr and 48 hr, respectively. The majority of progesterone
      metabolites recovered was excreted in feces (55%) versus urine (45%), whereas
      comparatively little of the recovered estradiol metabolites were excreted in
      feces (5%) compared to urine (95%). Intrasample variation in fecal hormone
      concentrations was extremely high but could be substantially reduced by
      extracting well-mixed fecal powder from freeze-dried samples, taken from the
      central or premixed portion of the wet sample. This method resulted in a close
      correspondence between matched serum and fecal progestins (mean correlation =
      0.81, range 0.61-0.94) collected from five nonpregnant adult females over a 7
      month period. Fecal estrogen profiles were more ambiguous, tending to overlap
      with those of fecal progestins. We conclude that analyses of fecal progestins can
      provide an effective, noninvasive means of characterizing ovarian activity in
      free-ranging African elephants.

PMID- 8998971
TI  - Potentiating effect of growth hormone on vitellogenin synthesis induced by 17
      beta-estradiol in primary culture of female silver eel (Anguilla anguilla L.)
      hepatocytes.
AB  - Previous in vivo experiments have indicated a potentiating role of growth hormone
      (GH) during experimentally induced vitellogenesis by 17-beta-estradiol (E2) in
      the female silver eel (Anguilla anguilla L.). To investigate whether GH has
      direct hepatic actions, the effects of hypophysial-purified and recombinant QH on
      vitellogenin (Vg) synthesis in response to E2 were tested on primary cultures of
      hepatocytes. Hepatocytes were prepared from control or E2-primed eels. Addition
      of E2 alone into the culture medium induced both Vg synthesis and secretion in a
      dose- and time-related fashion. Bovine growth hormone (bGH) alone had no effect
      on the induction of Vg synthesis or secretion. Bovine GH enhanced the in vitro
      effects of F2 on both Vg synthesis and secretion, an effect attenuated by an in
      vivo E2 priming which was dose-dependent with an ED(50) of 5 ng/ml. To
      investigate the specificity of GH action, purified eel and salmon GH and salmon,
      trout, and tilapia prolactins (PRL), as well as recombinant trout and tilapia GH,
      were tested, and the responses were compared to bGH. Purified salmon and
      homologous eel GH potentiated the vitellogenic response to F2. Recombinant GH
      were highly efficacious, excluding the presence of active contaminants in the
      potentiating effect of GH preparations. The potentiating effect of recombinant
      trout GH on the vitellogenic response was reduced at high doses (above 20 ng/ml),
      suggesting a down-regulation of GH binding sites by GH itself. Salmon PRL has
      minimal activity, but not trout and tilapia PRL, indicating that PRL is not an
      important potentiating factor on Vg synthesis in our model. It is concluded that
      GH acts directly on the liver to potentiate E2 induction of eel hepatic Vg
      synthesis. The potentiating effect of GH appears to be time- and dose-dependent
      and modulated as a function of hormonal status (E2 priming) of the eel.

PMID- 8998972
TI  - Adaptation of rainbow trout to seawater: changes in calcitonin gene-related
      peptide levels are associated with an increase in hormone-receptor interaction in
      gill membranes.
AB  - Transfer of trout from freshwater to seawater produced changes in plasma
      calcitonin gene-related peptide (CGRP), calcitonin, and calcium levels. Three
      days after transfer, the plasma CGRP concentration increased from 517 +/- 54 (n =
      6) to 1874 +/- 234 (n = 7) pg/ml. Ten hours after transfer, the plasma CT
      concentration in seawater-adapted trout was double the control value. Plasma
      calcium levels also changed: 2 days after transfer, the calcium increased 1.6
      fold over the basal value. The increased plasma CGRP level was correlated with an
      increased specific binding of CGRP to its branchial membrane receptors. Scatchard
      analysis of the data revealed this increase to be mainly due to increased binding
      affinity, as there was no difference in binding capacity between control and
      transferred animals. Carbonic anhydrase activity in branchial membranes increased
      2.2-fold over the control value 3 days after transfer. CGRP may thus play a role
      in osmoregulation and ionic balance.

PMID- 8998973
TI  - Cell survival and multiplication. The overriding need for signals: from
      unicellular to multicellular systems.
AB  - There are clear similarities in the control mechanisms for cell survival and
      multiplication in the two eukaryotes, the ciliate Tetrahymena thermophila and the
      yeast, Saccharomyces cerevisiae. Cell multiplication in both organisms is
      activated by the same compounds (phorbol esters, diacylglycerol, tetrapyrroles,
      etc.). These compounds also affect cell multiplication and other activities in
      mammalian cell systems. This homology in control mechanisms in two distinct
      groups of unicellular eukaryotes on the one hand, and in cells from multicellular
      animals on the other, leads us to propose that these cytoplasmic control
      mechanisms for cell survival and multiplication originated in the unicellular
      eukaryotes.

PMID- 8998974
TI  - Initial steps in the degradation of 3,4-dimethylbenzoic acid by Pseudomonas
      putida strain DMB.
AB  - Pseudomonas putida strain DMB capable of growing on 3,4-dimethylbenzoic acid as
      the only C and energy source was isolated by enrichment techniques. It does not
      utilize for growth or cooxidize the other dimethylbenzoate isomers tested. 3,4
      Dimethylsalicylic acid, 3,4-dimethylphenol and 3,4-dimethylcatechol were isolated
      and identified by nuclear magnetic resonance and mass spectra in the reaction
      mixture of P. putida washed cells. The detection of the two first metabolites
      suggests that the initial step in the degradation of 3,4-dimethylbenzoic acid is
      the formation of 3,4-dimethylcyclohexa-3,5-diene-1,2-diol-1-carboxylic acid which
      underwent an acid-catalyzed dehydration yielding 3,4-dimethylsalicylic acid and
      3,4-dimethylphenol. Further degradation proceeds through 3,4-dimethylcatechol via
      the meta pathway.

PMID- 8998975
TI  - An inducible expression system of histidine-tagged proteins in Streptomyces
      lividans for one-step purification by Ni2+ affinity chromatography.
AB  - An expression and purification cassette containing the aminoglycoside
      phosphotransferase gene (aph) as selective marker has been constructed in the
      Escherichia coli vector pULHis2. DNA fragments inserted in the cassette can be
      easily subcloned in pIJ699 to give vectors for overexpression of genes in
      Streptomyces and purification of proteins by a one-step procedure. The expression
      system uses the thiostrepton-inducible promoter tipA for expression and a six
      histidine coding nucleotide sequence that is fused in frame to the foreign gene
      inserted in the polylinker. The pULHis2-derived expression vector has been used
      satisfactorily to express and to purify the P7 and P8 proteins of Nocardia
      lactamdurans which carry out the methoxylation of cephalosporin C to 7
      methoxycephalosporin C.

PMID- 8998976
TI  - Iron utilization studies in Citrobacter species.
AB  - Seventy-one strains of Citrobacter were screened for iron scavenging mechanisms
      by biologic and chemical assays. Essentially all citrobacteria (70/71) were found
      to elaborate enterobactin-like siderophores by both biologic and chemical assays,
      however only c. koseri (C. diversus) was found to produce aerobactin. The
      concentration of ethylenediamine di(o-hydroxyphenylacetic acid) (EDDA) required
      to inhibit the growth of individual Citrobacter strains by depleting free iron
      ranged from 250 micrograms/ml to 100 micrograms/ml. Iron utilization studies of
      selected citrobacter isolates indicated that hemin and hematin could reverse the
      effects of iron limitation on growth under iron-stressed conditions (1000
      micrograms/ml of EDDA). Two C. koseri strains grown under iron-restricted
      conditions showed similar changes in their whole cell protein profiles including
      induction of high molecular mass proteins (72-83 kDa) which may play a role in
      iron acquisition under iron-stressed conditions. The collective results support
      an additional virulence-associated mechanism for C. koseri strains which may help
      explain the greater pathogenic potential this group has for causing serious
      extraintestinal disease in humans.

PMID- 8998977
TI  - Cooperative MetR binding in the Escherichia coli glyA control region.
AB  - We determined the relative binding affinity of the MetR protein for wild-type and
      mutant MetR binding sites 1 and 2 in the Escherichia coli glyA control region.
      The results show that MetR binding site 1 has a higher affinity for the MetR
      protein than binding site 2. In addition, the results suggest that binding of
      MetR to the glyA promoter is cooperative. Mutations that decrease the ability of
      MetR to bind to either site 1 or site 2 have no significant effect on MetR's
      ability to bend DNA.

PMID- 8998979
TI  - Sequential action of factors involved in natural competence for transformation of
      Neisseria gonorrhoeae.
AB  - We previously identified and genetically characterized several factors essential
      for the natural competence of transformation in Neisseria gonorrhoeae. Here we
      analyse the sequential action of these factors and dissect the overall
      transformation process into three distinct steps, (i) the sequence-specific
      uptake of transforming DNA into a DNase-resistant state, (ii) the transfer of DNA
      to the cytosol and (iii) the processing and recombination of the incoming with
      the resident DNA. While two pilus-associated factors, PilE and PilC, were
      previously implicated in the early DNA uptake event, we show here that three
      competence factors unrelated to pilus biogenesis, ComA, ComL and Tpc, are not
      essential for DNA uptake and rather act in a subsequent step. The respective
      mutants, however, lack the characteristic nucleolytic processing observed with
      the incoming DNA in both wild-type and non-transformable RecA-deficient N.
      gonorrhoeae, indicating that they are blocked in the processing and/or the
      delivery of DNA to the cytoplasm. A hypothetical model proposing a sequential
      action of the known gonococcal competence factors is presented.

PMID- 8998978
TI  - An autonomously replicating plasmid transforms Botrytis cinerea to phleomycin
      resistance.
AB  - A transformation system has been developed for the pathogen fungus Botrytis
      cinerea, based on the utilization of the wide host plasmid pUT737 that contains
      the Sh ble gene, conferring resistance to phleomycin. Transformed protoplasts
      were regenerated at 10-25 micrograms ml(-1) of phleomycin, at a frequency of 25
      40 transformants per microgram of DNA, and they were resistant up to 50
      micrograms ml(-1). Southern hybridization using undigested and digested total DNA
      showed the presence of circular autonomously replicating plasmid pUT737 in the
      transformants. Reisolated plasmid from transformed fungus transformed E. coli and
      rescued plasmid was identified as PUT737. Transformants were grown for four
      generations under non-selective conditions and replicative plasmids were still
      detected. Plasmids present in all transformants at this stage had been modified
      from native pUT737 and showed the same size and configuration indicating that
      selection through stabilizing plasmid forms has happened.

PMID- 8998980
TI  - Molecular cloning of a novel allele of SMR1 which determines sulfometuron methyl
      resistance in Saccharomyces cerevisiae.
AB  - A different mutation (SMR1B) to SMR1-410 (ilv2), which determines resistance to
      sulfometuron methyl in Saccharomyces cerevisiae, was cloned by PCR. Sequence
      analysis indicated a C to T change at position 575 of the ILV2 coding sequence,
      which results in a proline transition to leucine at position 192. Similarly to
      SMR1-410, the SMR1B gene was confirmed as a convenient dominant selective marker
      for yeast transformation including industrial strains.

PMID- 8998981
TI  - Promoter analysis of the catalase-peroxidase gene (cpeA) from Rhodobacter
      capsulatus.
AB  - The expression of the Rhodobacter capsulatus catalase-peroxidase (cpeA) was
      studied by in-frame fusions of the upstream region of the cpeA gene to a promoter
      less lacZ gene. The transcription of the cpeA gene is about 20-50-fold higher
      under aerobic-dark than under anaerobic-light conditions. The promoter was
      localized within a 69-bp upstream DNA region. The transcription start site,
      determined by primer extension, is 28 bases upstream from the initiation codon,
      confirming the postulated promoter localized by deletion analysis. Deletion of
      the part of the upstream region specifically responsible for oxygen regulation
      resulted in constitutive expression of the cpeA gene.

PMID- 8998982
TI  - Highly repetitive sequences and characteristics of genomic DNA in unicellular
      cyanobacterial strains.
AB  - Microcystis aeruginosa (Synechocystis) is a unicellular cyanobacterium that
      performs oxygenic photosynthesis. We found two novel sets of repetitive
      sequences, A (REP-A) and B (REP-B), on the M. aeruginosa K-81 genomic DNA, which
      consisted of distinct motifs of tandem repeated sequences located in the up- and
      downstream regions of the orf1 structural gene, respectively. Genomic Southern
      hybridization revealed multicopies of REP-A and -B on the genome. Furthermore,
      genomic Southern blots of cyanobacteria species with the REP-A and -B probes
      revealed that different hybridization signals appeared on the genomic DNAs of all
      12 Microcystis strains, but no signal appeared on those of Synechocystis sp. PCC
      6803, Synechococcus sp. PCC 7942, and Anabaena sp. PCC 7120.

PMID- 8998983
TI  - Cell transfer by filtration: evaluation of protocols for transformational
      competence.
AB  - Collection and washing of cells by centrifugation is a time consuming and
      inconvenient component of many microbiological protocols, especially when
      sterility must be maintained. Filtration onto disposable membrane filters
      efficiently replaced the centrifugation steps in standard transformational
      competence protocols for Escherichia coli, Haemophilus influenzae, and
      Saccharomyces cerevisiae. With all three protocols filtered cells were competent
      sooner and showed transformation efficiencies comparable to or higher than those
      of cells prepared by centrifugation. The procedure can be easily adapted to
      collect cells for many other purposes, and should be especially useful in
      metabolic studies and in preparing cells for electroporation, as it facilitates
      both thorough washing and rapid but gentle resuspension of cells without
      compromising sterility.

PMID- 8998984
TI  - The 18-kDa lectin-binding protein of Chlamydia trachomatis is different from the
      18-kDa histone-like protein.
AB  - Five proteins of Chlamydia trachomatis at the 18,000 (18-kDa) molecular mass
      region were resolved by two-dimensional electrophoresis. Three proteins at 18.2
      kDa, pI 6.9, 18.0 kDa, pI 6.3, and 17.9 kDa, pI 6.4 were shown to bind lectin. A
      fourth protein of 18.0 kDa at pI 10 was the histone-like protein. The fifth
      protein at 17.9 kDa, pI 7.0 was not characterized.

PMID- 8998985
TI  - Biochemical characterization of the carbapenem-hydrolyzing beta-lactamase AsbM1
      from Aeromonas sobria AER 14M: a member of a novel subgroup of metallo-beta
      lactamases.
AB  - AsbM1, a carbapenem-hydrolyzing beta-lactamase produced by Aeromonas sobria AER
      14M, was purified chromatographically, with anion exchange chromatography
      performed in the absence of Zn2+. The molecular mass of AsbM1 was approximately
      34,000; the isoelectric point was 9.1. AsbM1 had high hydrolytic specificity for
      carbapenems but low hydrolysis rates for penicillins and cephalosporins. AsbM1
      was resistant to the commercially available beta-lactamase inhibitors but was
      inhibited by pCMB and the chelators EDTA and o-phenanthroline. Zinc, an activator
      for many metallo-beta-lactamases, inhibited AsbM1 with an IC50 of 8 microM.
      Analysis of the N-terminal sequence (27 amino acids) showed 26% similarity to the
      CphA metallo-beta-lactamase. Because of the high specificity for carbapenems and
      the sensitivity to inhibition by Zn2+, AsbM1 should be included in a new subgroup
      of metallo-beta-lactamases.

PMID- 8998986
TI  - Examination of surface polysaccharides of Actinobacillus pleuropneumoniae
      serotype 1 grown under iron-restricted conditions.
AB  - We investigated the expression of important Actinobacillus pleuropneumoniae
      surface polysaccharides, namely, capsular polysaccharides (CPS) and
      lipopolysaccharides (LPS), after growth under iron-restricted conditions. Iron
      restriction did not seem to affect the production of CPS, as determined by
      labelling with a monoclonal antibody (mAb) against the serotype 1 K-antigen and
      flow cytometry analysis, and also as determined by electron microscopy. SDS-PAGE
      revealed that the LPS profiles of these cells were also unaffected by iron
      restriction. Using flow cytometry analysis, however, we observed that binding of
      mAb against serotype 1 O-antigen was altered in cells of A. pleuropneumoniae
      serotype 1 reference strain (4074) grown under iron-restricted conditions. This
      strain exhibited two subpopulations with distinct patterns of reactivity with the
      mAb against the O-antigen. When strain 4074 was grown under iron-restricted
      conditions, a shift from one cell subpopulation (moderately fluorescent) to
      another cell subpopulation (highly fluorescent, thus binding more antibodies) was
      observed. Our results indicate that growth of A. pleuropneumoniae serotype 1
      under iron-restricted conditions did not seem to affect CPS production, but might
      alter, at least for the reference strain, the expression of LPS.

PMID- 8998987
TI  - Genotyping human and bovine isolates of Cryptosporidium parvum by polymerase
      chain reaction-restriction fragment length polymorphism analysis of a repetitive
      DNA sequence.
AB  - In order to define transmission routes of cryptosporidiosis and develop markers
      that distinguish Cryptosporidium parvum isolates, we have identified 2
      polymorphic restriction enzyme sites in a C. parvum repetitive DNA sequence. The
      target sequence was amplified by polymerase chain reaction from 100 to 500
      oocysts and the amplified product was subjected to restriction enzyme digestion.
      Typing of 23 isolates showed that 10/10 calf isolates had the same profile. In
      contrast, 2 patterns were observed among human isolates: 7/13 displayed the calf
      profile, and 6/13 presented another pattern. The PCR-RFLP assay described here is
      a sensitive tool to distinguish C. parvum isolates.

PMID- 8998989
TI  - Desulfonation of aliphatic sulfonates by Pseudomonas aeruginosa PAO.
AB  - Pseudomonas aeruginosa PAO1 used a broad range of alkanesulfonic acids as sole
      sulfur source for growth, with molar growth yields of 2.2 to 2.9 kg protein per
      mol sulfur. 4-Phenylbutane-1-sulfonate was desulfonated in vivo to yield 4-phenyl
      1-butyric acid quantitatively as the sole product, suggesting that the
      desulfonation mechanism is the same as when alkanesulfonates serve as a carbon
      source for growth. This contrasts with aromatic sulfonate utilization in other
      organisms, where different desulfonation reactions are used to provide carbon and
      sulfur. Desulfonation of alkanesulfonates to provide sulfur was repressed by
      sulfate or thiocyanate, and derepressed in their absence. The alkanesulfonatase
      system is hence controlled as part of the sulfate starvation-induced stimulon.

PMID- 8998990
TI  - Behavioral analysis of single cells of Myxococcus xanthus in response to prey
      cells of Escherichia coli.
AB  - Myxococcus xanthus cells move over surfaces by gliding motility. The frz signal
      transduction system is used to control the reversal frequency, and thus the
      overall direction of movement of M. xanthus cells. We analyzed the behavior of
      wild-type and frz mutant cells in response to prey bacteria (Escherichia coli).
      Wild-type cells of M. xanthus did not respond to microcolonies of E. coli until
      they made physical contact. Cells which penetrated a colony remained in the
      colony until all of the prey cells were digested. Cells of frz mutants also
      penetrated E. coli microcolonies and digested some of the E. coli cells, but they
      invariably abandoned the microcolony leaving their food source behind. These
      observations illustrate the importance of the frz system of signal transduction
      for the feeding behavior of M. xanthus cells.

PMID- 8998988
TI  - Novel FNR homologues identified in four representative oral facultative
      anaerobes: Capnocytophaga ochracea, Capnocytophaga sputigena, Haemophilus
      aphrophilus, and Actinobacillus actinomycetemcomitans.
AB  - Based upon DNA sequence data and positive immunochemical reactivity of expressed
      protein, novel homologues of the FNR family were identified in four
      representative oral facultative anaerobes: Capnocytophaga ochracea,
      Capnocytophaga sputigena, Haemophilus aphrophilus, and Actinobacillus
      actinomycetemcomitans. The similarity to E. coli FNR and to HlyX (itself 71%
      similar to E. coli FNR, while regulating expression of hemolysin operon in
      Actinobacillus pleuropneumoniae) was estimated from the deduced partial amino
      acid sequence to be, in the above order of tested species, 98, 98, 86, and 85%,
      and 75, 75, 88, and 88%, respectively. The phylogenetic relatedness indicates a
      rather closer link of HlyX to the FNR homologues from both pathogens, H.
      aphrophilus and A. actinomycetemcomitans. The possibility that the A.
      actinomycetemcomitans FNR homologue functions as a redox-sensing transcriptional
      factor to regulate, in addition to anaerobic respiration, microaerobic expression
      of the leukotoxin operon (ltx gene) is suggested.

PMID- 8998991
TI  - Identification of a new prp locus required for propionate catabolism in
      Salmonella typhimurium LT2.
AB  - A new propionate (prp) locus of S. typhimurium was defined by mutation, was
      located to minute 8 of the chromosome, and was shown to be transcribed in the
      clockwise direction. A plasmid carrying the wild-type prp+ locus was isolated by
      complementation and its initial physical characterization is presented.
      Transcriptional regulation of prp was studied using MudI1734(lacZ+) operon
      fusions. Propionate stimulated prp transcription in a merodiploid strain
      containing prp+ and a prp::MudI1734 fusion, but failed to stimulate transcription
      of the same fusion in a haploid genetic background. prp transcription was reduced
      by a factor of 2 in strains deficient in the synthesis of the global regulatory
      protein FruR; fruR mutants failed to grow on propionate. Propionate blocked
      growth of prp mutants on medium containing succinate as carbon/energy source.

PMID- 8998992
TI  - Adhesion of bovine enterotoxigenic Escherichia coli (ETEC) by type 1-like
      fimbriae.
AB  - Enterotoxigenic Escherichia coli (STa+) strains were isolated from adult bovine
      with diarrhea. These strains did not express any known ETEC-specific adhesins.
      Although hemagglutination with rat and sheep erythrocytes was observed in the
      presence of D-mannose (MRHA), these strains also showed mannose-sensitive
      hemagglutination (MSHA) with guinea-pig erythrocytes. Electron microscopic
      studies revealed the presence of fimbria-like structures (provisionally called
      "F43ms") on bacterial cells grown at 37 degrees C but not on cells grown at 18
      degrees C. However, it was observed by SDS-PAGE that the J-1 strain (F43ms+)
      produces a protein similar to F1 fimbriae, and this strain hybridized with a DNA
      probe for F1 fimbriae. Immunogold-labelling techniques indicated that a rabbit
      anti-serum is specific for F43ms fimbrial structures, but not for Type 1
      fimbriae. The immunofluorescence test carried out with semipurified F43ms on
      bovine brush borders suggests that the fimbria-like structures are responsible
      for the adhesion to bovine epithelial cells.

PMID- 8998993
TI  - Characterization of malate dehydrogenase from deep-sea psychrophilic Vibrio sp.
      strain no. 5710 and cloning of its gene.
AB  - A metabolic key enzyme malate dehydrogenase (MDH) was purified from a deep-sea
      psychrophilic bacterium, Vibrio sp. strain no. 5710. The enzyme displayed an
      optimal activity shifted toward lower temperature and a pronounced heat lability.
      A gene encoding this enzyme was isolated and cloned. Recombinant Escherichia coli
      cells harboring the isolated clone expressed MDH activity with temperature
      stability identical to that of the parental psychrophile. Nucleotide sequencing
      of the gene revealed that its primary sequence was similar to that of a mesophile
      E. coli MDH (78% amino acid identity), for which the three-dimensional structure
      is known. The enzyme is thus suitable for the analysis of molecular adaptations
      to low temperatures.

PMID- 8998994
TI  - PCR amplification of the rDNA internal transcribed spacer region for
      differentiation of Saccharomyces cultures.
AB  - The size of the internal transcribed spacer (ITS) region as measured by gel
      electrophoresis of PCR products, amplified by primers ITS1 and ITS4, was over 800
      bp for all Saccharomyces sensu stricto species, but yeasts belonging to other
      Saccharomyces species had a shorter ITS region, making this characteristic
      potentially useful in the identification of Saccharomyces isolates. The ITS
      product length was homogeneous within the species Saccharomyces cerevisiae.

PMID- 8998995
TI  - Linker insertion analysis of the FimH adhesin of type 1 fimbriae in an
      Escherichia coli fimH-null background.
AB  - The gene encoding the Escherichia coli FimH adhesin of type 1 fimbriae has been
      subjected to linker insertion mutagenesis. Amino acid changes were introduced at
      a number of positions spanning the entire sequence in order to probe the
      structure-function relationship of the FimH protein. The effect of these
      mutations on the ability of bacteria to express a D-mannose binding phenotype was
      assessed in a fimH null mutant (MS4) constructed by allelic exchange in the E.
      coli K-12 strain PC31. Mutations mapping at amino acid residues 36, 58 and 279 of
      the mature FimH protein were shown to completely abolish binding to D-mannose
      receptors. Differences in the level of fimbriation were also observed as a result
      of some of the mutations in the fimH gene. These mutants may prove useful in
      dissecting receptor-ligand interactions by defining regions of the FimH protein
      that are important in erythrocyte binding.

PMID- 8998996
TI  - Genomic organization of purK and purE in Brevibacterium ammoniagenes ATCC 6872:
      purE locus provides a clue for genomic evolution.
AB  - From the genomic library of Brevibacterium ammoniagenes ATCC6872, the purE locus
      encoding 5'-phosphoribosyl-5-aminoimidazole (AIR) carboxylase (EC 4.1.1.21) was
      cloned and its nucleotide sequence was determined. From the sequence analysis,
      two distinct open reading frames (ORFs) in the sequence of the purE locus were
      identified as purK and purE genes (purK-purE). An in vivo translation experiment
      reconfirmed the purK and purE genes to be independent. The genomic organization
      in the purE locus of B. ammoniagenes is opposite to that of the bacteria
      Escherichia coli and Bacillus subtilis. However, it coincides with the fused
      genes (purKE) of higher organisms Saccharomyces cerevisiae, Schizosaccharomyces
      pombe and Vigna aconitifolia. This suggests that the purE locus might be an
      intermediate form for genomic evolution of bacteria to higher organisms.

PMID- 8998997
TI  - Simultaneous carriage of Candida albicans strains from HIV-infected patients with
      oral candidiasis: multilocus enzyme electrophoresis analysis.
AB  - Genetic diversity of 160 Candida albicans isolates from the oral cavity of 16 HIV
      infected adults prior to antifungal treatment was assessed using multilocus
      enzyme electrophoresis (10 C. albicans colonies were randomly chosen from each
      specimen culture). 20 electrophoretic types were distinguished from the analysis
      of 21 enzyme loci (10 were polymorphic). Five patients (31%) were found to be
      colonized by 2 or 3 genetically distinct strains. Nevertheless, in these five
      cases, one strain predominated (from 7 to 9 of the 10 colonies). Some HIV +
      patients with oral candidiasis appear to be simultaneously infected with several
      genetically different C. albicans strains before antifungal treatment.

PMID- 8998999
TI  - Cloning of a Bacillus sp. BP-23 gene encoding a xylanase with high activity
      against aryl xylosides.
AB  - The xynB gene encoding a xylanase from the recently isolated Bacillus sp. strain
      BP-23 has been cloned and expressed in Escherichia coli. The enzyme produced in
      this host shows a molecular size of 41 kDa and a pI of 4.5. The pH and
      temperature at which the highest activity was found were 5.5 and 50 degrees C
      respectively. Crude xylanase B showed activity on xylan, aryl xylosides,
      xylotetraose and xylotriose, while xylobiose was not hydrolyzed by the enzyme.
      Xylanase B showed high specific activity on aryl xylosides, probably as a result
      of the transxylosidase activity detected.

PMID- 8998998
TI  - Inducible production and cellular location of the epidermin biosynthetic enzyme
      EpiB using an improved staphylococcal expression system.
AB  - The antimicrobial peptide epidermin is distinguished by thioether amino acids
      such as meso-lanthionine, 3-methyl-lanthionine, and 2-aminovinylcysteine. The
      enzyme EpiB, encoded on a plasmid of the producing strain Staphylococcus
      epidermidis Tu3298, is very likely involved in the formation of these unusual
      amino acids. In order to obtain high-level production of EpiB, an improved
      staphylococcal expression vector based on the xylose-inducible xylA promoter of
      Staphylococcus xylosus was constructed. As shown by the expression of a lipase
      reporter gene, the new plasmid pTX15 mediated a considerably higher expression
      level after induction and a lower background expression level in the uninduced
      state than the previously described vector pCX15. The epiB gene was inserted in
      pTX15 and expressed in Staphylococcus carnosus. The EpiB protein was detected
      both in the cytoplasmic and the membrane fraction and was partially purified in
      three steps.

PMID- 8999000
TI  - Chromosomal variation in the southern short-tailed shrew (Blarina carolinensis).
AB  - Chromosomal polymorphism was assessed in the southern short-tailed shrew (Blarina
      carolinensis) using standard metaphase chromosome and G-banding techniques.
      Twenty-one animals (11 males, 10 females) from the Meeman Biological Station in
      Shelby Co., Tennessee, were examined for diploid number. Results showed diploid
      numbers of 35, 36, 37, 38, 39, 40 and 41 and fundamental numbers of 41, 42, 43,
      44 and 45. No diploid numbers or fundamental numbers were unique to a specific
      collecting locality. The first G-banded karyotypes are reported for the species.
      These results indicate that Robertsonian polymorphisms, inversions, and possibly
      other events are responsible for chromosomal variation in B. carolinensis.

PMID- 8999001
TI  - [Chronic venous insufficiency--from pathophysiology to therapy. 1:
      Pathophysiology--compression treatment--systemic pharmacotherapy].
AB  - At the core of chronic venous insufficiency (CVI) is valvular incompetence
      affecting the large veins, which results in ambulatory venous hypertension.
      Recent research has revealed the pathophysiological stages involved: damage to
      the endothelium of the vein, leukocyte trapping and, finally, inflammatory
      reconstruction of the vessel wall. Lymphangiopathy involving the small and large
      lymph vessels is always present. One of the measures capable of influencing
      elevated venous pressure is compression therapy, which is discussed in detail in
      the present article. Drug treatment is a rational supplement to curative
      therapeutic approaches to chronic venous insufficiency that in mild-to-moderate
      cases, can result in an alleviation of symptoms similar to that achieved with
      compression therapy.

PMID- 8999002
TI  - [Pathogenicity of fungi in the intestines--current status of the discussion].
AB  - The hypothesis that colonization of the intestinal tract by yeasts (e.g. Candida
      albicans) can lead to disease in immunocompromised individuals is currently being
      discussed controversially. Proponents assume that toxins produced by the fungi
      can trigger such complaints as irritable bowel syndrome of the chronic fatigue
      syndrome, and that such chronic or recurrent infections may be caused by an
      intestinal reservoir of yeasts. Opponents of the hypothesis, however, point out
      that no hard data on the pathogenetic significance of an intestinal reservoir of
      yeasts are available, controlled studies have failed to demonstrate the
      effectiveness of antifungal treatment. Discussions are however, hampered by a
      lack of objective data. The postulated pathomechanisms therefore need to be
      clarified, diagnostic criteria developed, and the efficacy of the proposed
      therapeutic measures shown by controlled studies. Until this has been done,
      assumption about the pathogenicity of yeasts in the bowel, cannot be taken as a
      basis for binding therapeutic recommendations.

PMID- 8999004
TI  - [Vaccinations in child- and adulthood. 3: Indication, special and travel
      vaccinations].

PMID- 8999003
TI  - [Endoscopy of the respiratory tract in childhood].
AB  - Technical developments in the field of pediatric bronchoscopy have expanded the
      diagnostic possibilities of this procedure while, at the same time making it less
      invasive: Today, almost all such examinations can be carried out on an outpatient
      basis and flexible fiberoptic instruments can be used in children who have
      reached school age with only analgesia and sedation. Technical innovations
      include endoscopic laser surgery, for example, to treat subglotic hemangiomas
      even in very young infants and endoluminal balloon dilatation for airway
      stenoses. These developments have improved and rendered less stressful the
      diagnosis and treatment of airway stenoses in children.

PMID- 8999005
TI  - [Antithrombocytic effectiveness of magnesium].
AB  - Platelet activation and subsequent intravascular thrombus formation play a
      central role in the pathophysiology of acute coronary syndromes. Extracellular
      magnesium has an antithrombotic action due mainly to its antiplatelet effect.
      High concentrations of magnesium inhibit platelet aggregation and adhesion in
      vitro and reduce the generation of prothrombotic eicosanoids. In addition,
      magnesium modulates the intracellular platelet activation cascade and decreases
      calcium influx. The function of major platelet membrane receptors, such as the
      fibrinogen receptor GP-IIb-IIIa and P-selectin are also inhibited by
      extracellular magnesium. Intravenous magnesium inhibits platelet function in vivo
      additive to aspirin. The antiplatelet effect of intravenously administered
      magnesium might be of benefit to patients with acute coronary syndromes when
      given before the development of an occlusive thrombotic plug.

PMID- 8999006
TI  - [85% of HIV infections are vertically transmitted].

PMID- 8999007
TI  - [Living organ donation for an unknown person--pure altruism? Little change in
      discussion of the transplantation law].

PMID- 8999008
TI  - [Prevention of sudden infant death. Infants of smokers are especially at risk;
      prone position is questionable].

PMID- 8999009
TI  - [Twins and triplets are more uncommon after fertility therapy today. Interview by
      Dr. rer. nat. Katharina Amheim].

PMID- 8999010
TI  - [The biggest wish: a completely normal in vitro child].

PMID- 8999011
TI  - [Modern fertilization techniques].
AB  - In Germany, some 17.2% of married couples are unintentionally childless. Of
      these, about one-third have a male factor infertility (with disordered
      spermatogenesis), which in part is unresponsive to drug treatment. In such cases,
      assisted reproductive techniques are giving childless couples new hope. The
      techniques are based on two principles: 1) in vitro improvement in semen quality
      in the laboratory, and 2) the overcoming of natural barriers to fertilization.
      The latter includes intra-uterine insemination (IUT), in vitro fertilization and
      embryo transfer (IVF/ET), gamete intrafallopian transfer (GIFT), subzonal sperm
      insemination (SUZI), zona pellucida drilling, and intracytoplasmatic injection of
      sperm (ICSI). ICSI has also used epididymal spermatozoa obtained by microsurgical
      aspiration (MESA) and sperm extracted from testicular biopsies (TESA). These
      methods have their own specific indications, contraindications and pregnancy
      rates. However, assisted conception techniques should not be considered outside
      the overall situation of the couple, including ethical, sociological,
      physiological and general medical problems.

PMID- 8999012
TI  - [Parenthood and child development after reproduction medicine treatment.
      Psychosomatic follow-up of 46 parents after assisted reproduction].
AB  - On the basis of a longitudinal study on "parenthood and child development after
      successful conception by IVF" in which 46 couples with 64 children born after
      reproductive medical treatment (IVF or ICSI) were followed up for three years, we
      now discuss several aspects of the psychological situation of those involved.
      Reference is made to the characteristics of the "structure" of the couples, their
      attitude towards the treatment, their experience of the pregnancy, features of
      child development and of the parent-child relationship, as well as to the
      prevailing psychological strategies of the couples for coping with the stresses
      and risks of assisted fertilization. Preliminary results show that during the
      course of treatment and following the birth of the children, the partnerships
      remained stable, and that relationships between family members are, for the most
      part, developing favorably.

PMID- 8999013
TI  - [A patient with Kartagener syndrome. Immotile cilia syndrome].

PMID- 8999014
TI  - [Pathogenesis of rheumatoid arthritis. Involvement of the humoral immune system-
      memory lymphocytes in synovial membranes].

PMID- 8999015
TI  - [Vaccinations in the established general practice--not a minor procedure. STIKO
      recommendations--where is vaccination insufficient, where superfluous
      vaccination?].

PMID- 8999016
TI  - [Vaccinations in child- and adulthood. 4: Vaccine reactions and side effects-
      storage and transport of vaccines].

PMID- 8999017
TI  - [Curcuma xanthorrhiza (Java tumeric) in clinical use].
AB  - The rhizome of Curcuma xanthorrhiza has been used for medical purposes for
      hundreds of years. A related plant, but which contains other constituents, is C.
      domestica, which is used in the manufacture of curry powder. Both experimental
      and clinical studies have revealed, in particular, a choleretic effect. In
      addition, in part in animal experimental studies, antilipidemic, analgesic
      antiphlogistic and antimicrobial effects have also been found.

PMID- 8999018
TI  - [Innovations from a middle class house. Interview by Dr. rer. nat. Till Uwe
      Keil].

PMID- 8999019
TI  - OK-432 injection therapy for lymphangiomas.

PMID- 8999020
TI  - [The value of oil baths for adjuvant basic therapy of inflammatory dermatoses
      with dry, barrier-disrupted skin].
AB  - The therapeutic value of oil baths for the treatment of dry skin with disturbed
      barrier function in atopic eczema, atopic xerosis, dry aged skin, exsiccation
      eczematid and psoriasis vulgaris is presented with special regard to modern
      concepts of epidermal barrier function. The use of oil baths with emollients as
      an integral and indispensable constitutent of maintenance therapy in dry skin
      conditions, atopic eczema and inflammatory dermatoses is reviewed.

PMID- 8999021
TI  - [Primary cutaneous osteoma in hereditary Albright osteodystrophy].
AB  - Cutaneous osteomas occur rarely; they represent the formation of bone in the
      skin. Primary and secondary forms of ossification can be distinguished. We
      describe the primary form of ossification in a child with Albright's hereditary
      osteodystrophy.

PMID- 8999022
TI  - [Shave therapy for surgical treatment of persistent venous ulcer with large
      superficial dermatoliposclerosis].
AB  - Ulcers in chronic venous insufficiency, especially in postthrombotic syndrome,
      are often resistant to compression therapy. They can be treated effectively by
      the dermatologic surgeon with a fairly simple operative procedure. The removal of
      the ulcer together with the extensive lipodermatosclerosis by Humby knife (shave
      therapy) and immediate grafting with a meshed split skin graft-possibly in
      combination with ligation of insufficient perforator veins-yields very good
      success rates. The results in 13 patients (18 legs) with an average follow up
      period of 11 months (up to 20 months) are reported.

PMID- 8999023
TI  - [Use of dermatography as treatment method in various medical specialties].
AB  - Dermatography is the application of tattooing techniques in medicine. In the
      past, several techniques were tried but none led to reproducible results.
      Dermatography has been improved over the last ten years, providing techniques
      which are both generally applicable and reproducible. It is a suitable treatment
      modality for permanently camouflaging disturbing discolorations and scars. This
      paper covers technical and medical aspects of dermatography, as well the
      indications.

PMID- 8999024
TI  - [Unfulfilled desire for children in the man: coping and pain. Results of a
      psychosomatic-andrologic cooperative study].
AB  - 115 andrological patients were studied with psychological self-assessment tests
      to assess both their motivation concerning parenthood, and their own explanations
      for the causes. Additionally self-esteem was evaluated in 51 patients. The main
      results were: Motivation concerning parenthood is of greater importance in coping
      with involuntary childlessness than objective andrological data. Patients assess
      their situation quite realistically; no tendency to misinterpret the medical data
      in order to defend negative feelings and to protect self-esteem could be found.
      Most patients with reduced fertility consider this situation a challenge and are
      willing to mobilize resources and the help of others in order to cope. Self
      esteem was only threatened in those patients with longlasting unvoluntary
      childlessness and little acceptance of medical infertility treatment and
      parenting substitutes, e.g. adopting a child.

PMID- 8999025
TI  - [Diagnosis, clinical aspects and therapy of early chromoblastomycosis in a case
      example].
AB  - Despite the availability of modern antimycotics, which produce high cure rates in
      early infections, the therapy of advanced chromoblastomycosis is still
      unsatisfactory. An initial chromoblastomycosis caused by a hitherto unidentified
      species of the genus Phialophora was diagnosed in a 46-year-old teacher. The
      organism was isolated twice at an interval of 6 weeks from a partly psoriasiform,
      partly verrucous lesion on the 4th toe. The infection was apparently acquired 4
      years ago during a holiday at Cape Verde. Treatment with itraconazole (Sempera).
      200 mg/day, and amphotericin B (Ampho-Moronal) cream for 6 weeks initially
      resulted in rapid regression. However, 4 weeks after cessation of therapy, the
      Phialophora species was cultured again from skin scrapings. Complete healing was
      achieved after re-treatment with itraconazole for 20 weeks at the same dosage in
      combination with topical amorolfine and local hyperthermia. Until now, no relapse
      has occurred. The present case demonstrates that this rare disease, which mainly
      occurs as a traumatic mycosis in the rural population of tropical regions, must
      be included in the differential diagnosis of psoriasiform or verrucous skin
      lesions and also included in the list of diseases which may be acquired while on
      vacation in exotic locations.

PMID- 8999026
TI  - [Erythema elevatum and diutinum in Crohn disease].
AB  - A 35-year-old woman suffering from Crohn's disease for 3 years developed painful
      erythematous nodular lesions predominantly on the dorsa of her hands and feet, as
      well as on her elbows and wrists. The clinical features and histopathological
      picture of leukocytoclastic vasculitis were both highly suggestive of erythema
      elevatum diutinum. No improvement of the skin lesions was observed during
      treatment with high doses of oral steroids. In contrast, treatment with dapsone
      resulted in a marked reduction of skin lesions. During a new attack of her
      Crohn's disease the erythema elevatum diutinum lesions flared again. The parallel
      clinical course of erythema elevatum diutinum and Crohn's disease, as well as the
      detection of immune complexes and neutrophilic granulocytes in lesions of both
      diseases, strongly suggest a common etiology. This hypothesis is discussed in
      context with this case and the recent literature.

PMID- 8999027
TI  - [Paraffinoma of the penis].
AB  - Paraffinomas of the male genitalia are now rare. We report on a Russian patient
      with subcutaneous nodules of the penis and the prepuce. Injections of exogenous
      lipids into the male genitalia are still performed in many Eastern European
      countries. Thus, a paraffinoma should be considered in the differential diagnosis
      of subcutaneous nodules of the male genitalia in patients from these areas.

PMID- 8999028
TI  - [Dermatitis bullosa striata pratensis caused by Dictamnus albus L. (burning
      bush)].
AB  - We report two patients with bullous phototoxic contact dermatitis caused by
      Dictamnus albus L. (gas plant) which belongs to the Rutaceae family. In both
      cases long lasting postinflammatory hyper-pigmentations were observed as a result
      of the phototoxic contact dermatitis. The phototoxic components of Dictamnus
      albus L. are the furocoumarins 5-methoxypsoralen (bergapten) and 8
      methoxypsoralen, and the alkaloid dictamnin whose phototoxic properties were
      recently discovered. Even though reactions to the gas plant have been
      infrequently reported, it is becoming more popular with gardenus and should be
      considered in the differential diagnosis of phototoxic contact dermatitis.

PMID- 8999029
TI  - [Malignant blue nevus with metastasis to lymph nodes and brain].
AB  - We report a patient who developed malignant transformation of a cellular blue
      nevus. At the age of 19 years the congenital, pigmented tumor on the left buttock
      was histopathologically diagnosed as cellular blue nevus. Thirty years later the
      tumor dramatically increased in size, involving the entire left buttock within
      several months. Multiple biopsies revealed the presence of a cellular blue nevus
      within the papillary dermis and an invasive, pleomorphic pigmented sarcoma in the
      depth of the tissue spreading into subcutis and skeletal muscle. Both benign and
      malignant cells were S100+, vimentin+ and HMB-45+, but only the malignant tumor
      cells stained positive for the proliferating cell nuclear antigen. General
      examination disclosed multiple metastases in the paraaortal lymph nodes and the
      retroperitoneum as well as a single brain metastasis. Despite palliative therapy
      with ionizing radiation and chemotherapy, the patient developed generalized
      metastases and died within weeks. This case clearly confirms that cellular blue
      nevi have the potential for malignant transformation and that the malignant
      variant may behave aggressively just as a malignant melanoma.

PMID- 8999030
TI  - [Metastatic malignant melanoma in treated non-Hodgkin's lymphoma].
AB  - Secondary cutaneous neoplasia, e.g. basal cell malignant carcinomas or squamous
      cell carcinomas, is frequently observed in patients with malignant lymphomas. The
      association between malignant lymphoma and secondary malignant melanoma has only
      been rarely reported. We describe a patient with a low-grade nodal B-cell
      lymphoma who, while on treatment with steroids and an alkylating agent, developed
      a malignant melanoma level IV which rapidly metastasized to lymph nodes involved
      by the malignant lymphoma.

PMID- 8999031
TI  - [Phototherapy of neurodermitis disseminata atopica].

PMID- 8999032
TI  - [A different truth. Supplement to the article "70 years Jena University
      Dermatologic Clinic--tradition and progress" by U. Wollina and R. Bonitz].

PMID- 8999033
TI  - [Comment on the contribution by J. Petres et al. Effective lymph node dissection
      in primary malignant melanoma].

PMID- 8999034
TI  - [Lyme borreliosis].

PMID- 8999035
TI  - Automated external defibrillators.
AB  - This study is an update to our August-September 1995 Evaluation of automated
      external defibrillators (AEDs) in which we evaluated nine AEDs from three
      manufacturers. In the current issue, we evaluate three additional semiautomated
      AEDs from three manufacturers. (We also present update information, including new
      rankings, for the previously evaluated units.) We tested the new units against
      the same criteria and rated and ranked them using the same scheme as in our
      original Evaluation. Specifically, we judged the suitability of these units for
      two primary clinical applications: prehospital use and in-hospital use. In
      addition, in this Update, we rated and ranked all of the units evaluated to date
      for a third clinical application: public access defibrillation (PAD) use. In this
      Update, we briefly describe the purpose and use of AEDs in the Introduction. For
      more detailed information about this technology, the environments in which AEDs
      are used, and the factors to consider when selecting this type of device, we
      encourage readers to refer to our original AED Evaluation (Health Devices 24[8
      9], August-September 1995). Also, because our criteria and test methods have not
      changed since the original study, we have not repeated them in this issue. Again,
      readers should refer to the previous Evaluation for this information.
      Furthermore, as described in the inset on page 272, the format of this Update
      differs from that of traditional Health Devices Evaluations. Most notably, all of
      the characteristics, test results, and ratings for each unit are presented in an
      individual Product Profile. Following the profiles for the three units, we
      present a comprehensive Conclusions section, detailing how the newly evaluated
      units compare with those evaluated in our original study.

PMID- 8999036
TI  - Conducting a staff meeting.

PMID- 8999037
TI  - Proceedings of the symposium on particle translocation across epithelial
      membranes. Belfast, July 1995.

PMID- 8999038
TI  - Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative
      signaling subunit conferring OSM-specific receptor activation.
AB  - Oncostatin M (OSM) is a cytokine whose structural and functional features are
      similar to other members of the interleukin (IL)-6 family of cytokines (IL-6, IL
      11, leukemia inhibitory factor (LIF), granulocyte colonystimulating factor,
      ciliary neurotrophic factor, and cardiotrophin-1), many of which utilize gp130 as
      a common receptor subunit. A biologically active OSM receptor has been previously
      described that consists of a heterodimer of leukemia inhibitory factor receptor
      (LIFR) and gp130. This LIFR.gp130 complex is also a functional receptor for LIF.
      We have cloned and characterized an alternative subunit (OSMRbeta) for an OSM
      receptor complex (a heterodimer of gp130 and OSMRbeta) that is activated by OSM
      but not by LIF. The signaling capability of specific receptor subunit
      combinations was analyzed by independent assays measuring cell proliferation or
      induction of acute phase protein synthesis. Our results demonstrate that both LIF
      and OSM cause tyrosine phosphorylation and activation of the gp130.LIFR
      combination, but the gp130.OSMRbeta complex is activated by OSM only. OSM-induced
      cellular responses, initiated through low affinity binding to gp130, are mediated
      by two heterodimeric receptor complexes that utilize alternative signal
      transducing subunits that confer different cytokine specificities to the receptor
      complex.

PMID- 8999039
TI  - [Immediate resection-anastomosis after intra-operative colonic irrigation in
      cancer of the left colon with obstruction].
AB  - In a consecutive series of 38 patients over 5 years, who required emergency
      surgery for obstructing left colonic carcinoma, 24 had primary bowel resection
      with immediate anastomosis, after intraoperative anterograde colonic irrigation.
      Complete colonic obstruction was present in all cases. There were 7 Dukes B
      tumors, 11 Dukes C tumors and 6 Dukes D tumors. The operative mortality was 8.3%
      (2 patients, with one from anastomotic leakage), anastomotic leakage rate was 4%.
      Superficial wound infection occurred in 4% of patients. The median postoperative
      hospital stay was 19.5 days. The Kaplan-Meier survival curve showed a 41%
      survival rate after 5 years. This technique was found to be safe and effective to
      perform a primary anastomosis, without requiring temporary colostomies, after
      emergency resection of selected left colonic carcinoma obstruction.

PMID- 8999040
TI  - [Oncocytic tumors of the thyroid. Diagnostic and therapeutic problems. Report of
      17 cases and review of the literature].
AB  - Histopathologic and clinical follow-up data of 17 patients observed 3-104 months
      (mean: 38 months) after operation for oncocytic tumors of the thyroid gland are
      presented. Mean patient age was 50 +/- 15 years. Benign and malignant lesions
      were respectively 13 and 4. Frozen sections were positive for benign and
      malignant lesions in respectively 7 and 2 cases. Total thyroidectomy was
      performed in all cases of malignant lesions and in 7 cases of benign lesion, the
      latter in order to treat high volume adenomas or associated controlateral
      lesions. No tumor relapse was observed during the follow-up period (data about 16
      patients). A review of the literature indicates that thyroid oncocytic adenoma
      diagnosis can be trusted and that this tumor is not especially prone to a
      malignant course with the mode of treatment applied. Thus total thyroidectomy
      should be recommended for: 1) malignant tumors. 2) and for selected benign
      adenomas depending on the tumor volume or on associated lesions.

PMID- 8999041
TI  - [Acute pancreatitis treated in a surgery ward. Apropos of 57 cases].
AB  - The aim of this study was to examine the results of a policy in the treatment of
      acute pancreatitis (AP): initial abstention, management in intensive care unit,
      surgery in cases of complication (infection and/or failure of medical treatment).
      The modalities of the surgical treatment were guided by CT scan findings:
      transperitoneal approach for diffuse lesions, posterior approach for localized
      lesions. From 1986 to 1994, 57 patients (32 males, 25 females, mean age 59.2
      years) were referred to our department for AP. Etiology was gallstones in 29
      cases, alcohol in 14 cases (Ranson < 3), moderate in 27 cases (Ranson < or = 5)
      and serious in 12 cases (Ranson > or = 6). According to the initial CT scan
      findings (56 cases), 9 patients were classified grade A, 11 grade B, 13 grade C,
      8 grade D ans 15 grade E. Thirty eight patients were managed conservatively (mean
      Ranson stage 3.3), while 19 patients underwent surgical treatment (mean Ranson
      stage 4.6), in emergency for misdiagnosis (4 cases), or secondarily because of
      failure of medical management (15 cases). Surgery consisted in necrosectomy with
      active drainage in 13 cases and drainage alone in 6 cases. Associated maneuvers
      included: cholecystectomy in 8 cases, cholecystostomy in 2 cases, jejunostomy in
      7 cases and colic resection for necrosis in 3 cases. Two patients (5%) managed
      conservatively died (multiple organ failure and cardiac insufficiency) while 4
      patients (21%: NS) who underwent surgery died (2 multiple organ failures, 1
      septic shock, 1 myocardic infarction). Mortality was correlated with the Ranson
      score: 42% for serious AP, 3.7% for moderate AP and nil for mild AP (p < 0.01).
      It was not correlated with CT scan grade, the onset or the type of operation.
      These results allow us to conclude that surgical treatment should be indicated
      only in cases of failure of conservative management, the best indication being
      uncontrolled sepsis. In this situation, active drainage provides good results
      since only one sepsis recurred among the 14 patients who underwent this
      procedure.

PMID- 8999042
TI  - [Value of fine-needle aspiration and extemporaneous examination in thyroid
      surgery. A prospective study of 1235 fine-needle aspirations and extemporaneous
      examinations in 846 patients].
AB  - We report a prospective study conducted from 1993 through 1995 in 846 patients
      (mainly women) consulting for a thyroid nodule. There were 465 multinodular
      goiters and 373 single nodules. The clinical diagnosis was obvious in 8 patients
      who were excluded. Pre-operative fine-needle aspiration was performed in 1235
      patients and per-operative extemporaneous examinations in 569. These two simple
      reliable examinations, with few significant complications in skillful hands, are
      complementary. Fine-needle aspiration gives reliable histology data for thyroid
      nodules and should always be included in the pre-operative workup. Extemporaneous
      pathology examination of the surgical specimen provides information for adapted
      surgery and avoids morbidity due to reoperation.

PMID- 8999043
TI  - [False hydatic aneurysm of the thoraco-abdominal aorta].
AB  - Arterial complications of hydatic disease are rarely encountered. We report a
      false hydatic aneurysm of the thoracoabdominal aorta revealed by ischemic
      embolism of the lower limbs. Surgical treatment included aorto-aortic prosthesis
      and albendazol for 6 months. Results at 18 months are excellent with negative
      hydatic serology. In endemic areas, hydatic disease is a possible cause of false
      aneurysms. Long-term surveillance is required after curative surgery and medical
      treatment.

PMID- 8999044
TI  - [Treatment of morbid obesity by adjustable silicone gastric banding. A new
      surgical technique of gastroplasty for obesity].
AB  - Among the various procedures used for surgical treatment of morbid obesity, the
      adjustable silicone gastric banding is in full development. It is also a gastric
      restrictive procedure and in addition it enables to adjust percutaneously the
      size of the stoma by inflating or deflating the inflatable portion of the band
      via an injection reservoir placed within the rectus sheath. In a small serie of
      15 patients the efficacity of adjustable silicone gastric banding seems to be
      similar to that of the vertical banded gastroplasty, as far as weight reduction
      and improvement in the obesity associated comorbidity are concerned. In addition,
      this technique has two major advantages: absence of failure from staple line
      disruption, and a good food tolerance because the stoma size is adjustable to the
      patient's need. In contrast to other gastroplasties, the adjustable silicone
      gastric banding procedure is fully reversible after cutting the prothesis, and
      can be done under laparoscopy.

PMID- 8999045
TI  - [Surgical cure of postoperative eventrations with intraperitoneal implantation of
      dacron mesh. Apropos of 160 operated cases].
AB  - A series of 160 patients with large incisional hernia underwent surgical repair
      involving the intraperitoneal positioning of a Dracon mersh. All patients were
      reexamined three years after operative procedure. Mortality was 1.2%. Four
      patients (2.5%) presented deep wound infection with removal of the mesh. Seven
      recurrences (4.3%) were reported. In conclusion, large incisional abdominal
      hernia can be treated successfully by an intraperitoneal Dracon mesh.

PMID- 8999046
TI  - [Lumbar hernia of the Grynfelt quadrant. Apropos of a case].

PMID- 8999047
TI  - [Villous adenoma of the duodenum. Apropos of a case].
AB  - We report a case of recurrent villous tumors (1989-1995) of the second duodenum.
      The diagnosis of these rare tumors was obtained by endoscopy. Risk of recurrence
      and degeneration raise the question of surgical or endoscopic treatment.

PMID- 8999048
TI  - [Uterine fibroma with ureteral inclusion. Apropos of a case].

PMID- 8999049
TI  - You and your associate.

PMID- 8999050
TI  - New Trends in Immunopharmacology 1995. Proceedings of a meeting. Tokyo, Japan,
      July 15, 1995.

PMID- 8999051
TI  - Inefficiency of upward displacement operating theatre ventilation.
AB  - A new thermally based ventilation system ('Floormaster') with inlet of cool clean
      air at floor level, and evacuation at the ceiling of the air warmed by activity
      in the room (upward displacement ventilation, 17 air changes/h) was compared with
      a standard positive pressure (plenum) ventilation system with air supply through
      an inclined perforated screen along one wall at the ceiling and evacuation at
      floor level (conventional turbulent or mixing system, 16 air changes/h). The
      study was made during rigidly standardized sham operations (N = 20) performed in
      the same operating room by a six-member team wearing non-woven disposable or
      cotton clothing. In general the upward displacement system removed dust particles
      too small to carry bacteria (0.16-<0.3 microm, 0.001<P<0.01) more efficiently
      than the conventional system. However, the displacement system also yielded two
      to threefold higher air and surface bacterial counts in areas important for
      surgical asepsis (wound area, instrument table) especially with regard to
      bacterial sedimentation (0.001<P<0.05). The major shortcoming of the displacement
      system was insufficient elimination of the larger bacteria-carrying particles.
      The type of clothing worn by the members of the team did not influence the
      overall results. We conclude that an upward displacement system will lead to
      increased counts of airborne and sedimenting bacteria and thus increase the risk
      of postoperative infection in comparison with conventional operating room
      ventilation systems.

PMID- 8999052
TI  - [Progress in diagnosis and treatment of renal diseases. I. Primary glomerular
      diseases. 1. Acute glomerulonephritis].

PMID- 8999053
TI  - [Progress in treatment and diagnosis of renal diseases. I. Primary glomerular
      diseases. 2. Chronic glomerulonephritis].

PMID- 8999055
TI  - [Progress in diagnosis and treatment of primary renal diseases. I. Primary
      glomerular diseases. 4. Crescentic glomerulonephritis].

PMID- 8999054
TI  - [Progress in diagnosis and treatment of renal diseases. I. Primary glomerular
      diseases. 3. Nephrotic syndrome].

PMID- 8999056
TI  - [Progress in diagnosis and treatment of renal diseases. II. Nephropathies
      associated with systemic diseases. Diabetic nephropathy with NIDDM].

PMID- 8999057
TI  - [Progress in diagnosis and treatment of renal diseases. II. nephropathies
      associated with systemic diseases. 2. Lupus nephritis].

PMID- 8999058
TI  - [Progress in diagnosis and treatment of renal diseases. II. nephropathies
      associated with systemic diseases. 3. Amyloidosis].

PMID- 8999059
TI  - [Progress in diagnosis and treatment of renal diseases. II. Nephropathies
      associated with systemic diseases. 4. Malignant nephrosclerosis].

PMID- 8999060
TI  - [Progress in diagnosis and treatment of renal diseases. III. Hereditary
      nephropathies and others. 1. Polycystic kidney].

PMID- 8999061
TI  - [Progress in diagnosis and treatment of kidney diseases. III. Hereditary kidney
      diseases and others. 2. Alport syndrome].

PMID- 8999062
TI  - [Progress in diagnosis and treatment of renal diseases. III. Hereditary kidney
      diseases and others. 3. Acute interstitial nephritis].

PMID- 8999063
TI  - [Progress in diagnosis and treatment of kidney diseases. III. Hereditary kidney
      diseases and others. 4. Chronic pyelonephritis].

PMID- 8999064
TI  - [Progress in diagnosis and treatment of kidney diseases. IV. Abnormal renal
      tubular functions. 1. Idiopathic edema].

PMID- 8999065
TI  - [Progress in diagnosis and treatment of kidney diseases. IV. Abnormalities of
      renal tubular functions. 2. Inappropriate ADH syndrome].

PMID- 8999066
TI  - [Progress in diagnosis and treatment of kidney diseases. V. Renal failure and
      kidney transplantation. 1. Acute renal failure].

PMID- 8999068
TI  - [Progress in diagnosis and treatment of kidney diseases. V. Renal failure and
      kidney transplantation. 3. Rejection reaction following kidney transplantation].

PMID- 8999067
TI  - [Progress in diagnosis and treatment of kidney diseases. V. Renal failure and
      kidney transplantation. 2. chronic renal failure].

PMID- 8999069
TI  - [Round-table discussion. Diagnosis and treatment of renal diseases: the current
      status and future prospect].

PMID- 8999070
TI  - [Case of C-type chronic hepatitis with manifestation of pituitary insufficiency
      caused by interferon therapy].

PMID- 8999071
TI  - [Case of cerebral anoxia displaying bilateral laminar necrosis at the entire
      periphery of the cerebral gray matter on MRI].

PMID- 8999072
TI  - [Case of Fitz-Hugh-Curtis syndrome].

PMID- 8999073
TI  - [Case of von Hippel-Lindau disease with pancreatic exocrine dysfunction and
      benign biliary stenosis due to multiple pancreatic serous cystadenoma].

PMID- 8999074
TI  - [Case of acute myelocytic leukemia (AML) with an increase in bone marrow
      basophils and morphological anomalies of 3 blood cell lineages].

PMID- 8999075
TI  - [Cardiovascular lesions in adult patients with history of Kawasaki disease].

PMID- 8999076
TI  - [Apoptosis and immunologic anomalies].

PMID- 8999077
TI  - [Possibilities for early discovery and early treatment of IgA nephropathy].

PMID- 8999078
TI  - [Expectations on internists].

PMID- 8999079
TI  - [Basis and clinical aspect of endocrine tumors].

PMID- 8999080
TI  - [Fundamental and clinical aspects of IgA nephropathy].

PMID- 8999081
TI  - [Cell death in digestive system diseases--molecular mechanism and clinical
      significance of cell proliferation].

PMID- 8999082
TI  - [Cerebrovascular disorders among Japanese].

PMID- 8999083
TI  - [Molecular mechanism and clinical aspects of blood cell production].

PMID- 8999084
TI  - [Endoscopic treatment of digestive system diseases. 1. Selection of endoscopic
      hemostasis applied to hemorrhage of the digestive system].

PMID- 8999085
TI  - [Endoscopic treatment of digestive system diseases. 2. Selection of endoscopic
      treatment to be applied to esophagogastric varices-- toward the establishment of
      outstanding and safest therapeutic methods].

PMID- 8999086
TI  - [Endoscopic treatment of digestive system diseases. 3. Results of endoscopic
      treatment of early stomach cancer and possibility for expansion of its
      application].

PMID- 8999087
TI  - [Endoscopic treatment of digestive system diseases. 4. Endoscopic resection of
      early stomach cancer and its relation to surgery].

PMID- 8999088
TI  - [Endoscopic treatment of digestive system diseases. 5. Laparoscopic
      cholecystectomy has become the gold standard of cholecystectomy].

PMID- 8999089
TI  - [Endoscopic treatment of digestive system diseases. 6. Application and limitation
      of endoscopic treatment in early colonic cancer].

PMID- 8999090
TI  - [Endoscopic treatment of digestive system diseases. 7. Evaluation of the
      therapeutic results of endoscopic treatment].

PMID- 8999091
TI  - [Treatment of diabetes mellitus and its complications. 1. Diabetic retinopathy].

PMID- 8999092
TI  - [Treatment of diabetes mellitus and its complications. 2. Diabetic neuropathies].

PMID- 8999093
TI  - [Treatment of diabetes mellitus and its complications. 3. Diabetic nephropathy].

PMID- 8999094
TI  - [Treatment of diabetes mellitus and its complications. 4. Diabetes mellitus and
      arteriosclerosis].

PMID- 8999095
TI  - [Treatment of diabetes mellitus and its complications. 7. Control of blood
      glucose and diabetic microangiopathy].

PMID- 8999096
TI  - [Diseases in the field of internal medicine and gene abnormalities. 1.
      Immunologic disease (Bruton's agammaglobulinemia)].

PMID- 8999097
TI  - [Diseases in the field of internal medicine and gene abnormalities. 2. Cancer of
      the digestive system and gene abnormalities].

PMID- 8999098
TI  - [Diseases in the field of internal medicine and gene abnormalities. 3. Gene
      abnormalities and diabetes mellitus--glucokinase gene and mitochondrial gene
      abnormalities].

PMID- 8999100
TI  - [Diseases in the field of internal medicine and gene abnormalities. 5. Nervous
      system diseases--molecular genetics of hereditary spinocerebellar degeneration].

PMID- 8999099
TI  - [Diseases in the field of internal medicine and gene abnormalities. 4. Molecular
      genetic analysis of hypertrophic cardiomyopathy among Japanese].

PMID- 8999101
TI  - [Gout and hyperuricemia].

PMID- 8999102
TI  - [Diagnosis and treatment of mycoses].

PMID- 8999103
TI  - [Approach to proteinuria].

PMID- 8999104
TI  - [Helicobacter pylori infection--from gastritis to stomach cancer].

PMID- 8999105
TI  - [Current status of asymptomatic myocardial ischemia].

PMID- 8999106
TI  - [Nutritional therapy of chronic obstructive lung diseases].

PMID- 8999107
TI  - [Malignant lymphoma--progress in management].

PMID- 8999108
TI  - [Recent progress in the management of Alzheimer disease].

PMID- 8999109
TI  - [Molecular biological approach to hypertension].

PMID- 8999110
TI  - [Process of articular destruction in chronic rheumatoid arthritis and its
      treatment with drugs].

PMID- 8999111
TI  - [Hemodialysis-associated amyloidosis].

PMID- 8999112
TI  - [Summer-type hypersensitivity pneumonitis].

PMID- 8999113
TI  - [Basic and clinical aspects of thrombopoietin].

PMID- 8999114
TI  - [Prion diseases].

PMID- 8999115
TI  - Rad Res 96. The Association for Radiation Research biennial general meeting.
      Birmingham, United Kingdom, 1-3 April 1996. Abstracts.

PMID- 8999116
TI  - A unique and sensitive ELISA technique for typing ABH antigens in bloodstains
      using UEA-I lectin--the removal of detergent with a Sephadex G-25 mini-column
      improves sensitivity.

PMID- 8999117
TI  - First impressions. A 21-yr-old woman with adenocarcinoma of the pelvis. What is
      the radiopharmaceutical? What are the findings?

PMID- 8999118
TI  - Studies on the formulation and in vitro release of ophthalmic liposomes
      containing dexamethasone sodium phosphate.
AB  - Several liposome formulations containing Dexamethasone Sodium Phosphate (DSP)
      were characterised in this study. For this purpose, phospholipids (gel and liquid
      types) and charge inducers, with or without cholesterol, were employed as bilayer
      components. Liquid state (PL 100:SA and PL 100:SA:CHOL) and gel state (PL 90H:SA
      and PL 90H:SA:CHOL) liposomes were prepared in molar ratios of (7:1:2), (10:1:4),
      (7:1) and (10:1). The film technique followed by sonication and membrane
      extrusion were used for the preparation of DSP liposomes. Particle size and
      particle-size distribution of MLVs, entrapment efficiency, free DSP (in
      supernatant) and, phospholipid content were determined for the characterization
      of the liposomes. The characterized liposomes were investigated for in-vitro
      release and different profiles were observed. The in-vitro release rates were
      evaluated kinetically and the best fitting equation was found to be the Higuchi
      equation.

PMID- 8999119
TI  - Production of drug loaded microparticles by the use of supercritical gases with
      the aerosol solvent extraction system (ASES) process.
AB  - The aerosol solvent extraction system (ASES) uses a supercritical gas as non
      solvent for an organic solution of drug and polymer in order to form
      microparticles by a flocculation process. Due to the miscibility of organic
      solvent and supercritical gas phase, microparticles with residual organic
      solvents below 30 ppm are formed. This principle was tested to encapsulate model
      drugs such as hyoscine butylbromide, indomethacin, piroxicam and thymopentin. As
      a carrier, the polymer poly-L-lactide was used. The resulting microparticles were
      investigated with regard to particle formation, morphology, particle size, size
      distribution, and drug loading. With decreasing, polarity of the incorporated
      drug, an increasing extraction occurs which lowers the drug loading of the
      microparticles. The extraction capacity of the gas phase depends on temperature
      and pressure which determines density and polarity of the gas. The obtained
      results show that the production conditions have to be optimized for each
      drug/polymer combination. Totally non-polar drugs are completely extracted
      together with the organic solvent, however, polar drugs, and here especially
      peptides and proteins, are easy to incorporate with the ASES process.

PMID- 8999121
TI  - 5-Fluorouracil-loaded chitosan microspheres: preparation and release
      characteristics.
AB  - Cross-linked chitosan microspheres containing 5-Fluorouracil (5-FU) were
      prepared. Variables believed to be important for microsphere properties were
      examined; these included: drug and chitosan concentrations, cross-linking
      process, the type of oil, stirring rate and also additives. Initial 5-FU
      concentration, the type and concentration of chitosan, the viscosity of oil phase
      and glutaraldehyde concentration affected drug release from chitosan
      microspheres. 5-FU release from cross-linked chitosan microspheres is
      characterized by an initial rapid release of drug. Addition of substances such as
      alginic acid, chitin, agar, sodium caprylate and stearic acid changed the release
      properties of 5-FU microspheres.

PMID- 8999120
TI  - Chitosan microspheres of diclofenac sodium: I. application of factorial design
      and evaluation of release kinetics.
AB  - In this study microspheres of diclofenac sodium, an anti-inflammatory agent, were
      prepared by utilizing a natural polysaccharide, chitosan-H. The objective of this
      investigation was to sustain the action of diclofenac sodium and to show the
      effect of various conditions on release kinetics. For this reason factorial
      design experiments were performed. The independent variables in the 3(3)
      factorial design were chitosan-H concentration, tripolyphosphate concentration
      and stabilization time, and in the 3(2) factorial design were chitosan-H and
      tripolyphosphate concentrations. The dependent variables, t50% and the total drug
      content were investigated by the polynomial equations. The release profiles were
      evaluated kinetically and the best fit was obtained by the Higuchi equation.

PMID- 8999122
TI  - Coating alginate beads with cross-linked biopolymers: a novel method based on a
      transacylation reaction.
AB  - Stable membranes were formed around alginate beads using a transacylation
      reaction between polysaccharidic esters, namely propylene glycol alginate (PGA)
      or pectin, and various proteins (human serum albumin (HSA), ovalbumin, bovine
      hemoglobin, lactoserum proteins). In a standard procedure, two reagents (PGA or
      pectin+protein) were added to a Na-alginate solution: beads were formed by
      dropwise addition into a calcium solution. Then the transacylation reaction was
      started by alkalinization of the bead suspension. A membrane was formed around
      the beads, made of a protein directly bound to a polysaccharide through amide
      linkages. The thickness of the membranes and the lysis time in trypsin were
      increased by raising the amount of NaOH used for the transacylation step. In a
      modified procedure, coated beads were obtained, incorporating PGA in the initial
      Na-alginate solution, and HSA in the transacylation bath. Activated charcoal was
      encapsulated in HSA-PGA beads, giving particles with adsorption properties
      towards creatinine. Assays were performed using PGA associated with alkaline
      phosphatase as the membrane-forming protein. Stable beads were obtained having a
      relative activity of 39.3%, as compared with free enzyme.

PMID- 8999123
TI  - Characterization of enzyme immobilization in liposomes prepared from
      proliposomes.
AB  - This study investigated the influence of ionic strength, liposome net charge and
      enzyme concentration on the immobilization of chymotrypsin in liposomes obtained
      from proliposomes. Depending on ionic strength and chymotrypsin concentration,
      immobilization efficiencies (IE) as high as 96 and 68% were obtained for
      liposomes prepared with Pro-lipo 3045 S and Pro-lipo 3080 S respectively.
      Increasing ionic strength and enzyme concentration resulted in a decrease in IE
      for both types of liposomes, and this was more pronounced for ionic strength.
      Relatively high amounts of chymotrypsin were found to be immobilized on the
      surface of the liposomes. Hydrophobic interactions between chymotrypsin and the
      hydrophobic tails of the phospholipids during liposome formation were probably
      responsible for this phenomenon.

PMID- 8999124
TI  - Formulation and release kinetics of cephalexin monohydrate from biodegradable
      polymeric microspheres.
AB  - Sustained release cephalexin microspheres have been formulated with poly(L-lactic
      acid) for intraperitoneal administration. Microspheres were prepared with spray
      dried cephalexin by phase separation in organic solvent containing a fixed
      concentration of polymer, then sieve-sized. Batch-to-batch reproducibility of
      microsphere size distribution and encapsulation efficiency ( > 95%) were
      demonstrated. The quality of the microspheres was dependent on the rate of
      stirring during preparation and was highest as 400 rpm. Scanning electron
      micrographs revealed approximately spherical shapes and porous surfaces. The
      release of cephalexin followed second order dissolution model kinetics for
      multiparticulate systems. The apparent second order rate constant, k2, was lowest
      for the highest sieve-size fraction (250-425 microns) and varied with drug
      loading reaching a minimum at 33% w/w. A lower molecular weight PLA of 50 000
      produced a faster release of cephalexin from microspheres. Cephalexin was
      released from microspheres for at least 4 h compared to only 10 min for complete
      dissolution of an equivalent weight of cephalexin powder, indicating sustained
      release which may be appropriate in treating localized infections.

PMID- 8999125
TI  - Effect of microcapsule size and polyisobutylene concentration on the release of
      theophylline from ethylcellulose microcapsules.
AB  - Ethylcellulose microcapsules containing theophylline were prepared by the phase
      separation coacervation process induced by non-solvent addition in the presence
      of variable amounts of polyisobutylene. No statistical difference was evident
      between the different sized microcapsules with respect to their drug content,
      wall thickness and in-vitro drug dissolution profiles. Poly-isobutylene was,
      however, found to influence the release profiles of drug to a great extent. An
      increase in polyisoburylene concentration retarded the release of theophylline
      from the microcapsules due to the formation of smaller and spheroidal coacervate
      droplets in larger volumes, which resulted in the formation of more evenly coated
      microcapsules. Although the release of theophylline from the microcapsules was
      found to fit both the first order and diffusion controlled release processes,
      differential rate treatment indicated that the overall release, in fact, was
      governed by diffusion controlled process.

PMID- 8999126
TI  - Preparation and characterization of polylactic acid microspheres containing water
      soluble dyes using a novel w/o/w emulsion solvent evaporation method.
AB  - Polylactic acid (PLA) microspheres containing soluble dyes as water-soluble model
      compounds were prepared using the water-in-oil-in-water (w/o/w) emulsion solvent
      evaporation method. Addition of electrolytes such as NaCl or CaCl2 into the
      external aqueous phase significantly improved brilliant blue (BB) entrapment
      efficiency compared to the case of no additives. NaCl was the most effective for
      obtaining high entrapment efficiency (80-90% of theoretical BB content). The
      average diameter of the obtained microspheres was in the region of 10-20 microns
      in all cases. PLA microspheres containing 5 and 10% (w/w) BB exhibited the so
      called burst release. The release rate decreased with decrease in the internal
      aqueous droplet volume in the preparation process. In particular, with PLA
      microspheres containing 5% (w/w) BB, those prepared with the smallest internal
      droplet volume (63 microliter), the initial burst release was reduced
      significantly, and 50% (w/w) of the loaded BB remained in the microspheres for 7
      days.

PMID- 8999128
TI  - [Problems on medical statistical process--wrong application].

PMID- 8999127
TI  - [Analysis of axonal transport using video microscopy].

PMID- 8999129
TI  - [Histochemical and biological characteristic of skeletal muscles of stroke-prone
      spontaneously hypertensive rats].

PMID- 8999130
TI  - [Isometric muscle exercise and anabolic steroid administration for prevention of
      regressive muscular atrophy].

PMID- 8999131
TI  - Getting research into practice.

PMID- 8999132
TI  - In vitro efficacy of a compound derived from garlic against Pneumocystis carinii.

PMID- 8999133
TI  - [The dual effect of ketamine on dopamine release from rat pheochromocytoma (PC
      12) cells].
AB  - Ketamine is known to increase arterial pressure and heart rate with its
      sympathomimetic action. However, it also relaxes vascular smooth muscle and
      causes hypotension. We studied such a bipartite effect in terms of ketamine
      induced changes of dopamine (DA) release from rat pheochromocytoma (PC-12) cells
      as a model of sympathetic nervous system. Without KCl stimulation, ketamine
      increased the DA release from PC-12 cells in a dose-related fashion (10(-4)M: 2.6
      +/- 0.4, 10(-3)M : 7.5 +/- 0.3, 10(-2)M: 27.1 +/- 3.2%). The similar increase of
      DA release was observed with absence of extracellular Ca2+. Exposure of KCl (50
      mM) to PC-12 cells increased the DA efflux from 1.7 +/- 0.4 to 14.2 +/- 0.8% (P <
      0.001). The release of DA stimulated by KCl (50 mM) was reduced to 9.0 +/- 1.0%
      and 11.4 +/- 0.3% in the presence of ketamine 5 x 10(-4)M and 10(-3)M
      respectively, and increased with the ketamine concentration of 10(-3)M. These
      findings indicate that ketamine depresses DA efflux related to membrane
      depolarization (K+) but it promotes a number of spontaneous DA efflux.

PMID- 8999134
TI  - [A patient who manifested various symptoms following severe accidental
      hypercapnia].
AB  - A case of severe accidental hypercapnia during anesthesia is presented. A 44-year
      old woman underwent laparotomy under general anesthesia. Forty minutes after the
      start of the operation, BP rose slightly and HR increased from 110 to 140 x min
      1. Then ST segment depression was noted on ECG monitor. Therefore, nitrous oxide
      was discontinued for 20 minutes. Frequent oxygen supply with oxygen flush was
      needed to inflate the collapsed bag. The operation was concluded without
      additional clinical problems. The patient remained unconscious after the
      anesthetics were discontinued. Cyanosis was observed despite the delivery of 100%
      oxygen. Cardiac arrest occurred following abrupt bradycardia, but she responded
      immediately to resuscitation. She was in a deep comatose state and did not
      respond to painful stimuli. The pupils were fully dilated with absent light
      reflex. Arterial blood gas analysis revealed; pH 6.720, PaCO2 277 mmHg, PaO2 159
      mmHg, and BE-16.2. Disconnection of anesthetic circuit was noted, thereafter, and
      hyperventilation was performed. Then, the pupils became promptly constricted and
      the response to painful stimuli appeared within 30 minutes. Her level of
      consciousness recovered completely after 4.5 hours of hyperventilation. She
      suffered from refractory hypotension (BP70-85 mmHg in systolic pressure) in spite
      of catecholamine administration, tachycardia (HR 140-160 x min-1) and ARDS in the
      ICU, but all the symptoms disappeared by the 16 hours after ICU admission.

PMID- 8999135
TI  - [Preclinical study of therapeutic agents used against Mycobacterium avium complex
      infections--with special reference to new macrolides and new quinolones].

PMID- 8999136
TI  - [In vitro anti-MAC activities of new quinolones in focus (1)].

PMID- 8999137
TI  - [In vitro anti-MAC activities of new quinolones in focus (2)].

PMID- 8999138
TI  - [The present status of treatment of Mycobacterium avium complex infection].

PMID- 8999139
TI  - [Pilot studies on the treatment of Mycobacterium avium complex lung disease--new
      macrolides and new quinolones. (1) Continuous positive cases (failure of the
      initial chemotherapy)].

PMID- 8999140
TI  - [Pilot studies on the treatment of Mycobacterium avium complex lung disease--new
      macrolides and new quinolones. (2) Multi-drug chemotherapy for initial cases on
      trial].

PMID- 8999141
TI  - [Decompensated pulmonary heart: topical aspects of management].

PMID- 8999142
TI  - [Endogenous digoxin-like factor in myocardial infarction].
AB  - The main aim of the study was to test the hypotheses that (a) concentrations of
      endogenous digoxin-like factor (EDLF) are increased in the initial period after
      acute myocardial infarction (AMI) and (b) may contribute to the onset of
      ventricular arrhythmias. 54 patients of both sexes with a first transmural AMI
      were included in a retrospective study. Plasma concentrations of EDLF were
      measured repeatedly during days 1-14 after AMI using DELFIA digoxin
      fluoroimmunoassay. 16 male patients with unstable angina pectoris and suspected
      AMI as well as 8 healthy subjects of both sexes served as controls. Plasma
      concentrations of EDLF in patients during the first day of AMI were increased
      (1.25 + (-)0.26 ng/ml, digoxin equivalents, p < 0.05) as compared with both
      healthy controls (0.34 + (-)0.08 ng/ml) and patients with unstable angina
      pectoris (0.4 + (-)0.06 ng/ml). First day after AMI plasma levels of EDLF in 7
      patients with primary ventricular fibrillation were higher (2.54 + (-)0.67 ng/ml,
      p < 0.03) than in 47 patients without ventricular fibrillation (1.05 + (-)0.27
      ng/ml). In 14 patients with AMI and congestive heart failure (class III, Killip)
      plasma concentrations of EDLF were significantly lower (0.32 + (-)0.09 ng/ml, p <
      0.03) than in 40 patients with AMI without congestive heart failure (1.51 + (
      )0.32 ng/ml). Starting from the second day of AMI plasma EDLF decreased to the
      level of control and did not change during two weeks of observation. These
      results, being in agreement with our previous experimental data, show an increase
      of plasma EDLF after AMI and suggest that EDLF may be involved in myocardial
      ischemia-induced arrhythmogenesis and participate in pathogenesis of congestive
      heart failure after AMI.

PMID- 8999144
TI  - [Approaches to perfection of Reaferon therapy in hepatitis B].

PMID- 8999143
TI  - [Antiphospholipid syndrome in SLE males].

PMID- 8999145
TI  - [Endocarditis in systemic lupus erythematosus].

PMID- 8999146
TI  - [Treatment of allergy by oral hyposensitization].

PMID- 8999147
TI  - [Duodenal ulcer: clinical significance of adaptation defects in the system of
      neurohumoral regulation].
AB  - Radioimmunoassay was used to determine prostaglandin (PGE-2) and cyclic
      nucleotides (cAMP and cGMP) concentrations in the serum before, 1 and 2 hours
      after standard test breakfast (5066 kJ) in 65 patients with duodenal ulcer. Basal
      hyperproduction of prostaglandins and cyclic nucleotides were interpreted as an
      adaptation-compensatory mechanism. The unbalance of their aftermeal reactions
      persistent even in ulcer healing may belong to factors of the disease
      progression.

PMID- 8999149
TI  - [Changes in the content of fats, neutral sterols, bile acids and carbonic acids
      with short chain in the feces from patients with chronic pancreatitis].

PMID- 8999148
TI  - [Disturbance of regional blood flow and activity of lipid peroxidation in
      recurrent ulcer and their drug correction].
AB  - Regional blood flow and intensity of free-radical lipid peroxidation were
      evaluated at rheogastrography and biochemically (quantitation of malonic
      dialdehyde and antioxidant serum activity), respectively, in 25 patients with
      recurrent ulcer. Recurrent ulcer is shown to induce disturbances in gastric wall
      regional hemodynamics due to activated vascular tone, reduced arterial blood
      inflow and venostasis. Lipid peroxidation became overactive and decreased defence
      potentialities of gastroduodenal serum. Oleum Hippopheae which is a natural
      antioxidant, improves regional hemodynamics by relaxation of overstrained
      vessels, stimulation of arterial blood inflow and relief of venous congestion.
      Overactive lipid peroxidation declines, antioxidant activity of the serum
      improves, especially in gastric ulcer, ulcer defect repair runs more actively.

PMID- 8999150
TI  - [Prostaglandins E concentration in gastric mucosa and synthesis of interleukin-1
      (IL-1) in different clinical variants of gastric ulcer].
AB  - Measurements of serum IL-1 levels and PGE-2 content in biopsies from gastric
      mucosa at ulcer margins were made in 30 patients with gastric ulcer running
      differently. The highest IL-1 production and low PGE-2 levels were typical for
      healing ulcer. Cicatrization was accompanied with normalization of IL-1 and PGE-2
      values. Gastric ulcer with a severe course exhibited inhibited IL-1 synthesis and
      decreased production of PGE-2.

PMID- 8999151
TI  - [Frequency of lyme borreliosis and diagnostic titers of antibodies to borrelia
      burgdorferi in patients with neurological diseases in endemic region of Russia].
AB  - The frequency of diagnostic titers of antibodies to Borrelia burgdorferi in 289
      examinees suffering from neurological diseases made up 10.4%, while in the
      population this figure was under 1.9%. Lyme-borreliosis was detected in 11 (3.8%)
      patients, 2 of them had mixed infection with tick-borne viral encephalitis. In 10
      patients (3.5%) the diagnosis of neuroborreliosis required verification with
      other techniques. It is thought valid to perform serological screening for
      neuroborreliosis only in patients with tick-born encephalitis to identify mixed
      infection.

PMID- 8999152
TI  - [New aspects of anti-inflammatory therapy of rheumatic diseases: preclinical
      validation and clinical trial of meloxicam].

PMID- 8999153
TI  - [Antibodies to cardiolipin and tumor-associated antigens CA-125 and CA-19-9 in
      patients with ovarian tumors].
AB  - Antibodies to cardiolipin (ACL) were detected in 12 (35%) of 34 patients with
      tumors of the ovaries. 8 of 12 patients exhibited clinical signs of
      antiphospholipid syndrome, 9 (75%), 2 and 1 patients demonstrated isolated
      hyperproduction of IgG ACL, combined rise of IgG ACL and IgM ACL, IgM ACL,
      respectively. Most frequently ACL occurred in endometriosis of the ovaries and
      serous cystadenomas (50 and 60%, respectively). In 5 (42%) of 12 patients CA-125
      antigen concentration was above the upper norm (35 U/ml), in 3 (25%) cases the
      level of CA 19-9 antigen was elevated. There were parallel changes of ACL
      concentration and tumor marker CA-125 before and after operation. Autoimmune
      origin of ovarian endometriosis is suggested.

PMID- 8999155
TI  - [Some factors of atherosclerosis risk in obese youths].
AB  - A total of 215 obese youths aged from 15 to 20 years were studied for lipid and
      carbohydrate metabolism, blood pressure and hormonal factors that regulated them
      (the performance of the thyroid gland and zona fasciculata of the adrenal
      cortex). The majority of the examinees revealed such atherosclerotic risk factors
      as arterial hypertension, diabetic pattern of carbohydrate metabolism disorders
      and type IIB, IV and IIA atherogenic dislipoproteinemia. In patients with
      juvenile dispituitarism there was dysfunction of hypophyseoadrenal systems which
      probably was important in pathogenesis of lipid and carbohydrate disbolism and
      arterial hypertension in them.

PMID- 8999154
TI  - [Pain syndrome in gastroenterological practice: potentialities of evaluation].
AB  - Qualitative and quantitative characteristics of chronic pain syndrome and their
      possible use in assessing analgetic effects of treatment were studied in 16, 49,
      26 and 17 patients with gastric ulcer, duodenal ulcer, chronic pancreatitis,
      chronic colitis, respectively. Pain was measured with the use of McHill's
      questionnaire modification and visual-verbal-analog scale. In addition to routine
      analysis of the data from the respondents, graphic mean profiles of pain for each
      group have been devised. There were differences in quantitative parameters of
      pain syndrome depending on nosological unity and profiles of patients. The
      questionnaire proved rather informative in evaluation and gradation of analgetic
      effects of therapeutic factors in ulcer patients.

PMID- 8999156
TI  - [Incidence of Helicobacter infection in adolescents with and without
      gastroduodenal diseases].

PMID- 8999158
TI  - [Case of life-time diagnosis of renal angiomyolipoma].

PMID- 8999157
TI  - [Systemic mycoses: therapy with a new antifungal drug diflucan].
AB  - A new antifungal drug of systemic action diflucan (Pfizer, USA) has been tried in
      10 patients (mean age 35.9 + (-)3.7 years) with various disseminated mycoses. The
      drug was used in a daily dose 200 mg intravenously or orally for 23.6 + (-)3.3
      days. The response was achieved in all the patients with disseminated mycoses
      caused by yeast fulgi. Side effects were not registered.

PMID- 8999159
TI  - [Fatal pulmonary hemorrhage in a male patient with microscopic polyarteritis].

PMID- 8999161
TI  - [Measles in adults: clinical characteristics].

PMID- 8999160
TI  - [Allergic drug-dependent lesions of the lungs].

PMID- 8999162
TI  - [Endoscopic treatment of late-stage cardiospasm].

PMID- 8999163
TI  - [Correction of duodenal motility in acute pancreatitis].

PMID- 8999165
TI  - [Hypophyseal and sex hormones in Chernobyl' emergency team members with
      neurocirculatory dystonia].

PMID- 8999164
TI  - [Clinicoimmunological features and treatment of acute intestinal infection of
      Proteus etiology].

PMID- 8999166
TI  - [Laser therapy of acute hepatic encephalopathy in patients with hepatitis B].

PMID- 8999167
TI  - [Current conception of calcium antagonists use in cardiology. A. L. Miasnikov
      Research Institute of Cardiology].

PMID- 8999168
TI  - [Peptic ulcer and reparants].

PMID- 8999169
TI  - [New gastroenterological prospects of ursodeoxycholic acid].

PMID- 8999170
TI  - [Prominent Russian surgeon IP Aleksinskii].

PMID- 8999171
TI  - [Tolstoi's acquaintances from medical profession].

PMID- 8999172
TI  - [The use of methotrexate in rheumatology: results and prospects].

PMID- 8999173
TI  - [Protracted viral hepatitis A].

PMID- 8999174
TI  - [Chronostructure of ectopic heart activity in the acute phase of myocardial
      infarction].
AB  - 7-day monitoring of cardiac rhythm has been conducted in 42 patients with
      myocardial infarction (MI) and 15 patients with chronic ischemic heart disease.
      Hour-by-hour analysis of extrasystole demonstrates that probability of
      ventricular arrhythmia is maximal in transmural MI, the first 3 days of acute MI
      are most arrhythmogenic. Follow-up of ventricular ectopic activity (VEA) showed
      the latter to significantly enhance early in the morning, afternoon and on the
      first 5 days after midnight. In unpenetrating MI, VEA intensifies in the morning,
      afternoon and postmidnight hoars. Atrial ectopic activity (AEA) in transmural MI
      enhances early in the morning, afternoon and at night (on the first 3 days). AEA
      in unpenetrating MI is more intensive late in the morning and afternoon.

PMID- 8999175
TI  - [Prevention of myocardial infarction: priorities, principles, realities].

PMID- 8999176
TI  - [The patient's phenotype and myocardial ponticuli].

PMID- 8999177
TI  - [Dynamic exercise tests in the assessment of rehabilitation in patients with
      myocardial infarction].
AB  - 176 patients with myocardial infarction were subjected to a sequence of tests: an
      original gravimetric test on the disease day 7-10, bicycle ergometry on day 12
      20, repeated bicycle ergometry on days 30-35 and 100-120. The results of the
      investigations performed in different times were interrelated. This helped to
      make accurate prognosis of recovering ability in 85% of patients. This system of
      dynamic control demonstrated that the greatest positive effects on exercise
      tolerance are reached in combined use of intravenous blood radiation with He-Ne
      laser and combined chemotherapy. Nitroglycerin+heparin combination is the least
      effective. Nitroglycerin+heparin in combination with metabolism correctors is of
      moderate efficacy.

PMID- 8999179
TI  - [The effects of plasmapheresis on central hemodynamics and cerebral circulation
      in hypertensive patients].
AB  - Plasmapheresis used in 61 patients with stage II hypertension brought a stable
      fall in arterial pressure and clinical response. Hypotensive drugs were reduced
      in doses or even discontinued. In subjects with hyperkinetic circulation arterial
      pressure went down due to decreased cardiac output. In hypokinetic hemodynamics
      hypotensive effect occurred because total peripheral resistance diminished.
      Lowering of arterial pressure was associated with positive changes in cerebral
      circulation. Plasmapheresis proved effective in all hypertensive subjects: in
      both hypo- and hyperkinetic circulation.

PMID- 8999178
TI  - [Magnito-, electro- and echocardiography in detecting symptoms of the
      "hypertensive heart"].
AB  - The study compared diagnostic potential of magnetocardiography (MCG),
      electrocardiography (ECG) and echocardiography (echo-CG) in 18 patients with
      arterial hypertension (AH). 32 healthy males served as control. Elements of MCG
      from normal subjects have been analyzed morphologically in 36 points of
      precordial leads. Left ventricular hypertrophy was registered at echo-CG, MCG,
      ECG in 11 (61%), 16 (84%) and 7 (34%) of the AH patients, respectively. Left
      atrial hypertrophy was discovered primarily by echo-CG and MCG. Defects in
      ventricular repolarization were recorded by MCg in 7 (39%) patients basing on
      MCG, echo-CG and rarely ECG signs of left ventricular hypertrophy. MCG is
      recommended as an effective tool in diagnosis of "hypertensive heart".

PMID- 8999181
TI  - [Long-term results of therapy for idiopathic hypothyrosis depending on the immune
      status].
AB  - Impaired immunity in patients with idiopathic hypothyrosis affects negatively the
      disease course. Such patients developed exacerbations more frequently than
      patients with normal immune characteristics.

PMID- 8999180
TI  - [Thyroid function in neurocirculatory dystonia].
AB  - Hypothalamopituitarythyroid system was studied using radioiodine tests,
      radioimmunoassay in 268 patients with neurocirculatory dystonia (NCD). Tissue,
      humoral immunity and nonspecific resistance of the body were assessed
      clinicoimmunologically. It is shown that eradication of chronic infection foci in
      NCD patients promoted positive changes in thyroid absorption, immune reactions
      and clinical condition.

PMID- 8999183
TI  - [Differential diagnosis of lymphadenopathies].

PMID- 8999182
TI  - [Magentotherapy in the comprehensive treatment of vascular complications of
      diabetes mellitus].
AB  - 320 diabetes mellitus (DM) patients were exposed to impulsed magnetic field, 100
      control DM patients received conservative therapy alone. 270 patients had
      microangiopathy, macroangiopathy was diagnosed in 50 patients. Good and
      satisfactory results of magnetotherapy in combination with conservative methods
      were achieved in 74% of patients versus 28% in control group. Metabolism
      stabilization resulted in some patients in reduced blood sugar. Use of magnetic
      field produced faster and longer response than conservative therapy.

PMID- 8999184
TI  - [Antibacterial therapy in irritable bowel syndrome].

PMID- 8999185
TI  - [Structural-metabolic features of uremic gastroenteropathy].
AB  - Concentrations of uremic toxins in the blood and jejunal juice of 72 patients
      with chronic renal failure (CRF) were studied as well as morphologic changes in
      biopsies from jejunal mucosa and submucosa, activity and location of acid and
      alkaline phosphatase as markers of intracellular and transmembrane transport. It
      was found that maximal excretion of uremic toxins in the jejunum occurs in CRF
      stage IIA and IIB. In terminal CRF excretion of uremic toxins delays from their
      concentration in the blood. This process is related with changes in enzymic
      processes. Histologically, all the examinees exhibited signs of chronic
      enteritis.

PMID- 8999186
TI  - [Various types of laser irradiation in the treatment of patients with non-healing
      duodenal ulcers].

PMID- 8999187
TI  - [Studies in twins to prove the immunogenetic heterogeneity of ulcer disease].

PMID- 8999188
TI  - [Use of Ditek in the treatment of patients with chronic obstructive bronchitis].
AB  - In moderate activity of inflammation observed in chronic obstructive bronchitis
      (COB) patients, ditek significantly improves external respiration and lesser
      circulation hemodynamics, inhibits lipid peroxidation and catabolism of cell
      receptors. COB with active inflammation required additional administration of
      antimicrobal medicine.

PMID- 8999189
TI  - [Retrovir in the treatment of acute viral hepatitis B].

PMID- 8999190
TI  - [Use of Diflucan in the treatment of chronic and recurrent candidosis with
      involvement of the esophagus].
AB  - Diflucan was used in 18 patients with chronic and recurrent candidiasis involving
      esophagus. The drug proved effective and safe. Recurrences were also responsive
      to diflucan.

PMID- 8999191
TI  - [A case of acute benzene poisoning causing pneumonia].

PMID- 8999192
TI  - [Fatal outcome in rotavirus infection].

PMID- 8999194
TI  - [Effectiveness of health resort therapy of medical patients].

PMID- 8999193
TI  - [Sarcoidosis in combination with chlamydiasis].

PMID- 8999196
TI  - [Attempt to formulate an updated classification of ulcer disease].

PMID- 8999197
TI  - [Balint groups in postgraduate training of general practitioners].

PMID- 8999195
TI  - [Cardioxan as a cardioprotector in antineoplastic chemotherapy].

PMID- 8999199
TI  - [The present state and ways of improvement of medicine distribution in Russia].

PMID- 8999198
TI  - [S.P. Botkin's and E.S. Botkin's work as personal physicians of the Czar].

PMID- 8999200
TI  - Standards for Economic Evaluation of Drugs: Issues and Answers. Proceedings of a
      conference. April 2-4, 1995.

PMID- 8999201
TI  - Methods controversies and agreement. Design and interpretation of evaluations.

PMID- 8999202
TI  - Methods controversies and agreement. Assessing quality and cost; design and
      interpretation of evaluations. Special commentary.

PMID- 8999204
TI  - The real world calls. Evolving operationalization of standards by users.

PMID- 8999203
TI  - Methods controversies and agreement. Assessing quality and cost; design and
      interpretation of evaluations.

PMID- 8999205
TI  - Standard development. Europe.

PMID- 8999206
TI  - Speaking from experience. Australia.

PMID- 8999207
TI  - Methods controversies and agreement. Assessing quality and cost.

PMID- 8999208
TI  - Standards development. The Canadian process.

PMID- 8999209
TI  - [The applicability and diagnostic effectiveness of transjugular liver biopsy].
AB  - BACKGROUND: The aim of this study was to evaluate the applicability, the
      diagnostic profitability and the incidence of complications associated with
      tranjugular liver biopsy associated with the measurement of the hepatic venous
      pressure gradient (HVPG). PATIENTS AND METHODS: The clinical histories of 829
      consecutive patients in whom transjugular liver biopsy was performed from 1982 to
      1993 were reviewed. The diagnostic value of the sample obtained was evaluated in
      all the patients and the HVPG determined. Moreover, the size of the greatest
      fragment obtained during biopsy was also determined. RESULTS: Material for
      histologic study was obtained in 95% of the cases. In 70% the biopsy was
      diagnostic, in 11% it provided data contributing to diagnosis and in 19% it was
      not useful. Potentially severe complications were presented in 0.8% of cases
      being fatal in one (0.1%). The obtention of a fragment of small size was
      significantly associated with the presence of disease with marked fibrosis and
      high HVPG. A HVPG > 10 mmHg in patients with a suspicion of liver disease had a
      sensibility of 92% and a specificity of 63% for the diagnosis of hepatic
      cirrhosis. In 83% of patients with a GPVH > 10 mmHg in whom the biopsy was not
      useful, the diagnosis of hepatic cirrhosis was performed by other methods.
      CONCLUSIONS: Transjugular biopsy in a safe, effective diagnostic method in
      patients with severe coagulation disorders. The appearance of the material
      obtained and the HVPG provide useful information for diagnosis although the
      biopsy is not diagnostic.

PMID- 8999210
TI  - [The legibility of written informed consent forms].
AB  - BACKGROUND: The generation of the use of informed consent forms makes necessary
      to grant their legibility for patients. Up to now, we didn't have in Spain a
      suitable yardstick for evaluating the reading levels. METHODS: A sample of 10
      texts of diverse procedence, 8 journals and 16 informed consent forms were
      collected. They were analyzed using the Grammatik 6.0 utility of the word
      processor Word Perfect 6.1, and four parameters were obtained: number of words,
      number of sentences, Flesch-Kincaid Grade Level and Sentence Complexity. In
      addition an Integrated Readability Level (LEGIN) was calculated. RESULTS: Flesch
      Level and Sentence Complexity give a suitable and complementary analysis of
      readability, which is enhanced by the LEGIN. The acceptably reading level is
      obtained when the Flesch-Kincaid Level is above 10, the Sentence Complexity is
      under 40 and, overcoat, the LEGIN is above 70. Just 5 of the 16 consent forms had
      the adequate LEGIN level. Another 5 had the Flesch correct levels and 7 the
      adequate Sentence Complexity. CONCLUSIONS: The Grammatik utility of the word
      processor Word Perfect 6.1 is a suitable yardstick to analyze the readability,
      but is necessary to complete the analysis with the LEGIN, to render more
      sensibility and especificity. It's mandatory to enhance the readability of
      written forms to grant the ethical quality of the informed consent process.

PMID- 8999211
TI  - [Vertical transmission of human immunodeficiency virus: six years of development
      1987-1992)].
AB  - BACKGROUND: According to World Health Organization estimates, from the beginning
      of the epidemics to the end of 1994, the number of children infected by human
      immunodeficiency virus (HIV) was 1.5 million. This paper describes the evolution
      of some clinical and epidemiologic characteristics of vertically transmitted HIV
      infection. PATIENTS AND METHODS: All children born to HIV-infected mothers who
      delivered at a university hospital in Barcelona, Spain, between 1987 and 1992,
      were included in the study. Rates of HIV vertical transmission, HIV infection
      incidence and mortality due to HIV were estimated, and trends for the study
      period analyzed. Odds ratios were used to assess associations between variables.
      RESULTS: 192 newborns were identified and allocated, with respect to the year of
      birth, in three cohorts of 71, 58 and 63 children. Overall HIV vertical
      transmission rate was 16.5% and did not differ between cohorts. Infection
      incidence density rates increased over time (0.2, 4.9 and 8.1 cases/100 child
      years, respectively; p = 0.016), while incubation periods decreased significantly
      (248, 103 and 114 days; p = 0.0004). There were no changes in mortality density
      rates (2.2 deaths/100 child-years). Regarding mothers' characteristics, a
      significant temporal trend (p < 0.001) for being older at delivery, belonging to
      the heterosexual transmission group and having symptomatic infection was observed
      over time. CONCLUSIONS: Certain clinical and epidemiologic aspects of HIV
      vertical transmission have changed over time, however the number of new cases has
      remained fairly constant. In our setting, both early diagnosis and clinical
      management of these children have improved, but primary prevention for HIV
      vertical transmission has not been effective. Better counselling for HIV-infected
      women of childbearing age is needed.

PMID- 8999212
TI  - [Calcium antagonists and their impact on risk of coronary disease].

PMID- 8999213
TI  - [Benign asbestos pleural effusion. Report of a first series in Spain].
AB  - Up to now, only 2 cases of benign asbestos pleural effusion have been described
      in Spain. We report our experience of 15 patients diagnosed of benign asbestos
      pleural effusion (BAPE). Between 1980 and January 1995, 15 patients were
      diagnosed of BAPE according to the following criteria: a) evidence of pleural
      effusion; b) previous asbestos exposure, and c) exclusion of other etiologies of
      last during 3 years of follow-up. Retrospective review of diagnostic and
      evolutive data from the patients' clinical records. Asbestos exposure was intense
      in 8 patients and slight in 7. There were 11 effusions on the left side and 4 on
      the right side. All effusions were exudative, with a pleural adenosine deaminase
      level lower than 43 U/l. Eleven patients had a lymphocytic pleural fluid. All
      patients had nonspecific pleural histology, and asbestos bodies were detected in
      one case. Eleven patients achieved a radiographic resolution in less than 3
      months, and 3 patients presented relapses. Fourteen patients had a good outcome,
      and one patient presented a lung adenocarcinoma after 5 years of follow-up.
      Benign asbestos pleural effusions are predominant on the left side, have a
      tendency to relapse and the exposition can be occasional. The outcome is good in
      most of the cases.

PMID- 8999214
TI  - [Exploratory-confirmatory perspectives of statistical biomedical applications:
      two dialogues (and II). Critical considerations concerning tests of
      significance].

PMID- 8999215
TI  - [Pattern of alcohol consumption in young people and associated problems].

PMID- 8999216
TI  - [MDMA or ecstasy: pharmacologic, toxicologic and clinical aspects].

PMID- 8999217
TI  - [Visceral leishmaniasis and ciprofloxacin].

PMID- 8999218
TI  - [Antiretroviral treatment for HIV infection].

PMID- 8999219
TI  - [Traffic accidents in the Spanish population: analysis from an emergency
      department].

PMID- 8999220
TI  - [Hepatitis due to lovastatin].

PMID- 8999221
TI  - [Ecology and abortion: opinions and fallacies].

PMID- 8999222
TI  - [The costs of AIDS: the adequacy of hospitalization to improve efficacy].

PMID- 8999223
TI  - [The methadone program is greatly reduced. Few addicts are referred to Uppsala].

PMID- 8999224
TI  - [Medical students are caught in a treadmill. Nothing helps--as long as health
      services are beaten].

PMID- 8999225
TI  - [Dilemma II of a general practitioner. From health care agreement to medical
      fees].

PMID- 8999226
TI  - [Informed consent: a rule with exception!].

PMID- 8999227
TI  - [Why question the SK courses?].

PMID- 8999228
TI  - [Adult age citizens have a right to wrong choices].

PMID- 8999229
TI  - [Is Swedish health care really bad?].

PMID- 8999230
TI  - [Why all these half measures in the tobacco debate?].

PMID- 8999231
TI  - [A paradox on amalgam by the National Board of Health and Welfare].

PMID- 8999232
TI  - [Confusion of concepts in the discussion on resource allocation].

PMID- 8999233
TI  - [The National Board of Heath and Welfare and myocardial infarction mortality].

PMID- 8999234
TI  - [A protective collar is mandatory for all ice hockey players].

PMID- 8999235
TI  - [The number of individuals with prescribed antidepressive agents has doubled].

PMID- 8999236
TI  - [A new series: health economics for health services].

PMID- 8999237
TI  - [A minor trauma can cause life-threatening bleeding. Varying course in eleven
      patients].

PMID- 8999238
TI  - [Motor neurons regenerate axons after CNS-injury. Surgery in cases of rotavulsion
      restore motor functions].

PMID- 8999239
TI  - [Reduce the dosage of ketorolac! Following EEC recommendations reduces the risk
      of hemorrhage with a marginal reduction of the analgesic effect].

PMID- 8999240
TI  - [Fistulas in the ear--diagnosis and therapy].

PMID- 8999241
TI  - [New medical techniques within urology - 1. Are expensive, new drugs better than
      surgery?].

PMID- 8999242
TI  - [New medical techniques in urology - 2. Does the patient have a right to
      choose?].

PMID- 8999243
TI  - [A SBU-report discovers lack of knowledge." No" to general prevention with
      estrogen after menopause].

PMID- 8999244
TI  - [Marketing becoming more and more sophisticated. Physicians are questioned about
      their prescriptions by drug industry].

PMID- 8999245
TI  - [A renewed island hospital concentrates on telemedicine. Connections with
      Huddinge will strengthen Visby hospital].

PMID- 8999246
TI  - [Terminal care should be based on humane principles! "No" to euthanasia and
      physician-assisted suicide].

PMID- 8999247
TI  - [County councils may be maintained if the customer's role is refined].

PMID- 8999248
TI  - [A survey of role playing based on correct methodology is welcome].

PMID- 8999249
TI  - [Ventilation of ice-skating rinks should be improved].

PMID- 8999250
TI  - [Establish a special pool for interns with exams from non-Nordic countries].

PMID- 8999251
TI  - [Establish neonatal intensive care at Huddinge hospital].

PMID- 8999252
TI  - [Ultrasound screening--quality assurance of the method is important].

PMID- 8999253
TI  - [New discoveries on oral contraceptives and risk of breast cancer. International
      data show a moderate increase in risk].

PMID- 8999255
TI  - [Abuse of data from registries 1. Uncertain data on infarction, results are
      exaggerated].

PMID- 8999254
TI  - [Alzheimer disease and related conditions. Increased knowledge. New preparations
      are on the way].

PMID- 8999256
TI  - [Misdirected quality efforts. Criticism of the survey by the National Board of
      Health and Welfare on myocardial infarction mortality in Swedish hospitals].

PMID- 8999257
TI  - [A case report. Myocardial infarct].

PMID- 8999258
TI  - [Report from an accused hospital. Mistakes by the National Board of health and
      Welfare are not to be repeated!].

PMID- 8999259
TI  - [Women's research. Research not only about or by women].

PMID- 8999260
TI  - [New curse of the urbanized world. Obesity--a still increasing epidemic].

PMID- 8999261
TI  - [Cryosurgery--an alternative in prostatic cancer].

PMID- 8999262
TI  - [Urologic irrigation fluid is not safe. There is evidence of serious adverse
      effects].

PMID- 8999263
TI  - [A symposium on drugs and adverse effects. Serious problems--but the debate needs
      balance].

PMID- 8999264
TI  - [A consensus statement on estrogen replacement after menopause].

PMID- 8999266
TI  - Spared an influenza pandemic for another year?

PMID- 8999265
TI  - Termination of Acute Stroke Studies Involving Selfotel Treatment. ASSIST Steering
      Committed.

PMID- 8999268
TI  - Use of gamma detecting probe and isosulphan blue to localize sentinel node in
      patients with malignant melanoma.
AB  - Elective lymph node dissection for patients with malignant melanoma remains
      controversial. Sentinel lymph node sampling has been recommended to select
      patients who will benefit from lymphadenectomy. Vital blue dye and a gamma
      detecting probe have been used to identify the sentinel node. Two patients are
      described in whom microscopic disease was identified in the sentinel node as the
      sole focus of metastasis. The ability to excise the sentinel node provides
      accurate pathologic and staging information, is cost effective, and minimizes the
      morbidity associated with a routinely performed lymphadenectomy.

PMID- 8999269
TI  - An unexpected clue: the peripheral blood smear in a patient with AIDS.

PMID- 8999270
TI  - Peregrine Wroth, M.D., and cynanche tonsillaris.

PMID- 8999267
TI  - Single (culprit) vessel disease in octogenarians with acute myocardial infarction
      and unstable angina.
AB  - It is generally thought that coronary artery disease (CAD) in octogenarians would
      involve multiple vessels. The purpose of the current study was to determine the
      relative importance of single vessel disease in octogenarians with acute
      myocardial infarction (AMI) and unstable angina and its outcome from a
      revascularization procedure such as percutaneous transluminal coronary
      angioplasty (PTCA) or coronary artery bypass grafting (CABG). Our study included
      70 patients (25 men, 45 women) aged 80 or older (mean, 84.5 +/- 0.5) admitted for
      the first time to the St. Agnes Hospital coronary care unit during 1994 for AMI
      or unstable angina. Patients admitted primarily for congestive heart failure,
      cardiogenic shock, hypertensive heart disease, or cardiomyopathy were excluded.
      Fifty patients (71.4%) had AMI and 20 (28.6%) had unstable angina. Of the 19
      patients who had cardiac catheterization done, 10 had single vessel disease, 8
      had flow-limiting disease in 2 or more coronary arteries, and 1 had no flow
      limiting disease. The mean ejection fraction was 56.5 +/- 6.9 in patients with
      single vessel disease, 48.0 +/- 3.3 in those with multiple vessel disease, and
      38.7 +/- 1.7 in those who did not have cardiac catheterization done. Fourteen
      PTCA (20%) and 3 CABG (4.3%) were performed without inhospital mortality from the
      procedures. There were 9 deaths (12.9%) overall: none among 10 patients with
      single vessel disease, 1 (12.5%) among 8 patients with widespread CAD, and 8
      (15.7%) among 51 patients who did not have cardiac catheterization. Study results
      emphasize the need for recognition and treatment of single vessel disease by
      revascularization procedures to reduce mortality from CAD in octogenarians.

PMID- 8999271
TI  - False memory syndrome--an issue clouded by emotion.

PMID- 8999272
TI  - Organized and ritual abuse.

PMID- 8999273
TI  - Physical aspects of alleged sexual assaults.
AB  - The medical evidence, detailing the physical findings, is just one component in
      the investigation of serious sexual assault and it is not for the doctor alone to
      determine the veracity of an allegation. This paper has described some of the
      factors which limit the quality and value of the medical evidence. Potential ways
      to rectify the problems are: 1. A requirement that all doctors who examine
      complainants of sexual assault should have undergone basic theoretical and
      practical training and be required to continue their education by attendance at
      update meetings and participating in peer review groups. 2. Large-scale, well
      designed research projects which relate the physical findings to the outcome of
      the case. 3. Routine colposcopic assessments with photo-documentation of the
      genital examinations of all complainants of serious sexual offences. 4. Pretrial
      debate amongst medical experts.

PMID- 8999275
TI  - Police investigations--separating the false and genuine.

PMID- 8999274
TI  - Sleep and sexual offending.

PMID- 8999276
TI  - Difficulties experienced in legal practice.

PMID- 8999277
TI  - Locating the stranger rapist.
AB  - As part of a larger project evaluating aspects of offender profiling, an initial
      study was undertaken of the geographic aspects of approximately 300 sexual
      offences carried out by 79 stranger rapists. The objective was to focus further
      research on the topic into potentially useful channels, but information thought
      to be of immediate use to investigating officers was also produced. It was
      ascertained that at least one-fifth of the sample of stranger rapists were
      itinerant to a greater or lesser extent. Analysis of the cases where both the
      offender's address and the location where he approached the victim were known,
      indicated that the majority of attacks (75 per cent) were initiated within five
      miles of the offenders' homes. The apparent reasons for victims being approached
      unusually far away included targeting of locations where numbers of suitable
      victims were available; raping during relatively sophisticated property offences;
      'prowling' or 'hunting' over large areas by subjects who spent considerable
      amounts of time so doing; access to transport; and familiarity with widely
      dispersed neighbourhoods, often due to the offender having lived in two or more
      locations. As a result of this work, future research on the geography of rape
      will be directed towards those aspects of the offences which have been identified
      as relevant to the distance between an offender's base and the site where he
      approached his victim.

PMID- 8999278
TI  - Cognitive-behavioural treatment of shoplifting in a depressed female.
AB  - This paper describes the successful treatment of a depressed shoplifter, using
      cognitive therapy combined with exposure, an approach not previously described in
      the literature for this problem. Definitions of shoplifting behaviour are
      discussed, and other treatment methods examined.

PMID- 8999279
TI  - The outcome of psychiatric recommendations to courts.
AB  - The case notes, court reports and outcomes of 699 consecutive out-patient
      referrals to a forensic service for court reports, related to criminal offences,
      were examined. The relationship between rejection of psychiatric recommendations
      to the court and a number of different variables was examined. Age, sex and
      ethnicity were found to be unrelated to rejection rates. Referrals from defence
      solicitors, certain offences and certain diagnoses were found to be over
      represented among those cases in which such recommendations were rejected.

PMID- 8999280
TI  - Custodial suicide in Australia: a comparative study of different populations.
AB  - Research on custodial suicide has run into immense difficulties in its attempt to
      identify common characteristics of the suicide-prone inmate. In 1993, Haycock
      recognized these difficulties and called for comparative research to delineate
      the different risks posed by different sorts of confined populations. This paper
      contrasts the characteristics of different categories of confined inmates based
      on data collected by the Australian Institute of Criminology on deaths in custody
      within Australia between the years 1980 and 1993, inclusive. This form of
      research will lead to a greater understanding of the phenomenon of custodial
      suicide and the establishment of better preventive strategies tailored to the
      needs of specific groups and organizations.

PMID- 8999281
TI  - Traumatic baso-brainstem subarachnoid haemorrhage.
AB  - Traumatic basal subarachnoid haemorrhage is an uncommon disorder that is well
      described in the forensic literature. The aetiology traditionally has been a
      relatively minor blunt trauma which is sustained typically at the level of the
      base of head and injures the arterial system to the brain. The site of trauma may
      be occult and not always demonstrable. In the case discussed, an acute baso
      brainstem subarachnoid haemorrhage was caused by a severed extracranial vertebral
      artery due to a stabwound injury to the upper neck. A gravitational factor and
      alcohol intoxication, which might contribute to the basal intracranial haematoma,
      is given a novel thought.

PMID- 8999282
TI  - Psychological trauma and its influence on genuine and false complaints of sexual
      assault.
AB  - Events that cause fear leave effects, both physical and psychological. In the
      last 20 years, it has been recognized that criminal assaults are also fearful
      events which, like war atrocities and civilian disasters, can have profound
      effects upon the psychological health of victims. In this paper, some of the
      research describing the psychological effects of crime will be reviewed, with
      particular emphasis on allegations of sexual assault. The impact of trauma on
      crime victims in relation to the prosecution process will be discussed, including
      the relevance of trauma to the issue of false allegations of sexual assault. The
      paper will conclude with some recommendations for research.

PMID- 8999283
TI  - Ageing and ovarian hormones. Proceedings of the International Menopause
      Symposium. Tampere, Finland, 23-24 March 1995.

PMID- 8999284
TI  - Extraction and characterization of the smooth-type lipopolysaccharide from
      Fusobacterium nucleatum JCM 8532 and its biological activities.
AB  - The lipopolysaccharide (LPS) of Fusobacterium nucleatum JCM 8532 was isolated by
      hot-phenol water extraction. Most of the LPS was extracted in the phenolic phase
      and shown to be the smooth-type, whereas the aqueous phase contained mainly rough
      type LPS. The chemical composition of the LPS was similar to that reported in
      other studies, but D-quinovosamine, which may be a major component of O-antigenic
      polysaccharide, and 3-deoxy-D-manno-2-octulosonic acid (Kdoi) were detected for
      the first time by gas chromatography-mass spectrometry. The biological activities
      of smooth-type LPS, including limulus activity, lethal toxicity, pyrogenicity,
      and B lymphocyte mitogenicity, were comparable to those of entero-bacterial LPS.
      Smooth-type LPS inhibited the cell growth and DNA synthesis of adult and fetal
      human gingival fibroblasts in a dose-dependent manner, suggesting that LPS may
      play a role in the occurrence of human gingivitis.

PMID- 8999285
TI  - Reduced anti-Pseudomonas aeruginosa activity of a cephalosporin, cefodizime, in
      rats whose neutrophils were selectively depleted by a monoclonal antibody.
AB  - In order to clarify the mechanisms of the in vivo antibacterial activity of a
      cephalosporin, cefodizime (CDZM), the effect of this antibiotic on Pseudomonas
      aeruginosa E7 infection was examined in rats whose neutrophils had been
      selectively depleted by monoclonal antibody RP-3. CDZM was less effective in RP-3
      treated rats than in untreated rats. However, treatment of rats with recombinant
      human granulocyte-colony stimulating factor (rhG-CSF) augmented the in vivo
      activity of this antibiotic. Furthermore, the in vivo antibacterial activity of
      two other cephalosporins, cefpimizole (CPIZ) and cefoperazone (CPZ), was
      bilaterally affected by a rise or fall in the neutrophil number, although to a
      lesser degree than was the case with CDZM. Taken together, neutrophils play an
      important role in the in vivo antibacterial activity of certain cephalosporins.

PMID- 8999286
TI  - Electron microscopic observation of the antibody-induced capsular swelling
      phenomenon in Klebsiella pneumoniae.
AB  - The capsular swelling phenomenon of Klebsiella pneumoniae strain 277 was examined
      morphologically using the electron microscopy techniques of freeze-substitution.
      The capsules of strain 277 measured about 52 nm in thickness, and were composed
      of a number of fine fibers. After treating the bacteria with anti-capsular serum,
      the size of the capsules increased to about twice the normal size and they lost
      their electron density. The capsular fibers that are tightly packed in normal
      cells became loose and thus the identification of the individual capsular fibers
      was difficult in the swollen capsules. Capsule swelling was induced by washing
      the cells with phosphate-buffered saline. The removal of either divalent cations
      or some other materials might thus be important for maintaining the normal
      capsule structure. the mechanism of the swelling phenomenon was also discussed.

PMID- 8999287
TI  - Typing of verotoxins by DNA colony hybridization with poly- and oligonucleotide
      probes, a bead-enzyme-linked immunosorbent assay, and polymerase chain reaction.
AB  - To identify the type of Verotoxins (VT) produced by Verocytotoxin-producing
      Escherichia coli (VTEC), a sensitive bead-enzyme-linked immunosorbent assay and
      polymerase chain reaction with common and specific primers to various VTs (VT1,
      VT2, VT2vha, VT2vhb, and VT2vp1) were developed. Together with colony
      hybridization tests with oligo- and polynucleotide probes, these methods were
      applied to VTEC isolates to type the VT produced. The toxin types of 26 of 37
      strains were identified, but the reaction profiles in assays of the remaining 11
      strains suggested the existence of new VT2 variants. The application of these
      identification procedures may be useful as a tool for clinical and
      epidemiological studies of VTEC infection.

PMID- 8999288
TI  - [Diabetes--yesterday, today, tomorrow].

PMID- 8999289
TI  - [The hypophyseal-adrenal axis in chronic alcoholism].
AB  - In order to reveal the morphologic basis of clinically recognized pseudo Cushing
      syndrome in chronic alcoholism, we performed an analysis of histologic
      characteristics of hypothalamo-hypophyseal adrenal axis components. The
      experiment included Wistar rats which were given 15% ethanol solution in water
      for three months. By methods of classical histology, histochemistry and
      immunofluorescence adrenal and hypophyseal sections of experimental animals
      exposed to continual effects of alcohol and those from the control group were
      examined. ACTH (adrenocorticotropin) cells of the experimental group show
      expressed immunofluorescence as a proof of their high secretory granules present
      in numerous cytoplasmic endings which contribute to significantly increased
      number of these cells comparing to the control group. In the adrenal cortex of
      animals exposed to alcohol, in the zona fasciculata and zona reticularis, under
      the influence of hypophyseal corticotropin (ACTH) secretion, there is a
      statistically significant increase of the compact cells region, as synthetic
      active elements, in regard to vacuolized cells, as inactive elements, which has
      been established stereologically. Simultaneous hyperfunction of hypophyseal ACTH
      cells and ACTH dependent zones of the adrenal cortex in chronic alcoholism,
      proves that alcohol primarily acts at the level of hypothalamus and hypophysis,
      while adrenals react to hypersecretion of ACTH cells. The way alcohol affects
      neurotransmitters is the topic of the discussion, whereas stimulated synthesis of
      acetylcholine is pointed out.

PMID- 8999290
TI  - [Immunologic characteristics of peritoneal fluid in endometriosis].
AB  - Increased volume of peritoneal fluid is found more frequently in patients with
      endometriosis (51%) than in infertile patients without endometriosis (13%).
      Immunologic analysis of the peritoneal fluid shows that in patients with
      endometriosis the level of immunoglobulin G (IgG) increases. We analyzed 34
      samples of peritoneal fluid from patients with and 13 from patients without
      endometriosis. The mean value of IgG in the group of patients with endometriosis
      was 7.73g/L and 3.94g/L in the control group. This difference is statistically
      significant, but there is no statistically significant difference in regard to
      immunoglobulin A (IgA), while it has been significant for immunoglobulin M (IgM)
      only in the third stage of the disease. In certain stages of illness there are no
      statistically significant differences in values of all three immunoglobulin
      types. A golden standard of immunoglobulin G in peritoneal fluid is 5g/L and in
      regard to this level we calculated the following: sensitivity, specificity,
      prognostic value and accuracy of the test. Sensitivity and positive prognostic
      value reached 85.3%. On the basis of these findings it can be concluded that if
      no endometriosis can be seen during laparascopy while the volume of peritoneal
      fluid is increased, immunologic analysis should be performed. If IgG values are
      5g/L or higher, the patient should be treated as a patient with possible
      "precursor endometriosis".

PMID- 8999291
TI  - [The effect of actinomycin D on electroencephalographic activity in the rabbit
      brain].
AB  - DNA, RNA and cellular proteins are of great importance in regard to the following
      processes: learning, memorizing and storage of memory. That is why protein
      synthesis blockers are successfully used in investigations of these brain
      functions. Aktinomicin D (AMD) is such a substance; it is an antibiotic which is
      used in treatment of some malignant diseases, but on cellular level it disturbs
      RNA synthesis. Experiments were carried out on Chinchilla rabbits with
      chronically implanted electrodes for registration of electroencephalographic
      activity. Intracerebroventricularly applicated Aktinomicin D disturbs the
      appearance of habituation after rhythmic repetition of electrocutaneous
      stimulation of the same characteristics which clearly points to the importance of
      preserved cellular protein synthesis in the processes of learning.

PMID- 8999292
TI  - [Relation between the abdominal sagittal diameter, fat tissue distribution and
      metabolic complications].
AB  - Numerous epidemiological and clinical studies point to association of android
      type of obesity with metabolic complications, such as glyco-regulation,
      hyperlipoproteinemia, accelerated atherosclerosis which all lead to
      cardiovascular diseases. As the waist-hip ratio did not prove to be specific
      enough for determining association between fat tissue distribution and risk from
      development of obesity complications, measurement of the sagittal abdominal
      diameter has been established. Studies carried out up to now reveal that there is
      a better connection between these measurements and obesity complications. A group
      of 45 women was examined: 30 obese and 15 healthy non-obese women being the
      control group. The following was measured: body height, body weight, waist and
      hip circumferences, blood pressure, body mass index (BMI), waist-hip ratio (WHR)
      and a special caliper was used to measure the sagittal abdominal diameter. In
      order to study glyco-regulation all obese women underwent GTT (Glucose tolerance
      test) with determination of insulinemia; in regard to lipidic parameters total
      cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins (LDL)
      cholesterol and index of atherosclerosis were determined. Gathered results show
      that in the group of obese women values of sagittal abdominal diameter were
      significantly higher than in the control group, while metabolic parameters show
      that in these patients there is a metabolism disorder of lipids and lipoproteins
      as well as hyperinsulinemia and reactive hyperinsulinemia and higher values of
      systolic and diastolic blood pressure. Our results of examination in the group of
      android obese women show that there is a significant association among values of
      sagittal abdominal diameter and lipid disorders, disorders of glycoregulation,
      especially hyperinsulinism and insulin resistance.

PMID- 8999293
TI  - [Clinical use of erythropoietin].
AB  - Humoral regulation of erythropoiesis has been known for 100 years, while clinical
      utilization of recombinant human erythropoietin (rhEPO) only for two decades. It
      can be said that there is much experience in regard to indications, models and
      results of its clinical utilization. According to the standpoint of secretion of
      erythropoietin, anemias can be divided into those where secretion is increased
      and satisfactory, those where it is increased but not satisfactory and into those
      where it is not increased or it is even decreased. Anemias of the first group are
      not an indication for rhEPO utilization, the second group is relative and the
      third group absolute indication for its utilization. The best results are
      achieved with absolute indications and it is anemia in chronic renal
      insufficiency and nonphysiologic anemia of premature babies. Good results can be
      expected, but not predicted in relative indications, such as anemias in chronic
      infections, anemias in malignant diseases, myelodysplastic syndrome, aplastic
      anemia and other secondary anemias. Utilization of rhEPO is useful also in
      certain states without anemia, especially in transfusiology.

PMID- 8999295
TI  - [Fever of unknown origin].
AB  - Febrile episodes of unknown origin are a great challenge for physicians
      practitioners, but often a great problem too, as they remain unsolved in a
      certain percentage of patients. Increased temperature is the most common
      characteristic of infections, so that is why febrile episodes of unknown origin
      are mostly part of the practice of epidemiologists. This study shows that febrile
      episodes of unknown origin can be caused by a great number of other diseases and
      gives the sequence of diagnostic procedures in regard to the age and subjective
      difficulties as well as therapeutic approach to solving the cause of the febrile
      episode of unknown origin.

PMID- 8999294
TI  - [Gangliosides as neurobiochemical markers].
AB  - Gangliosides are primary brain membrane lipids which, due to their localization,
      present specific markers of certain nerve cells. Their structure and content is
      tightly connected with cytogenesis and histogenesis of brain in mammals. Their
      biologic function, at the surface of the neurons' membrane, is important for
      bioelectric neuronal activity and synaptic transmission. Apart from that,
      gangliosides are important as receptors of bacterial toxins. Effects that
      gangliosides may have on dendrites' and axons' growth have been studies and it
      can be concluded that they have a significant impact on recovery of ischemic
      brain lesions. They are also important therapeutic and diagnostic markers of
      certain malignant tumors. The most valuable results are expected in future by
      examination of gangliosides metabolism in neurologic diseases by application of
      cell cultures.

PMID- 8999296
TI  - [Surgical treatment of compressive lumbar radiculopathy].
AB  - In the period 1982-1991, 1511 patients with compressive degenerative lumbar
      radiculopathy underwent surgery at the Clinic of Neurosurgery in Novi Sad. 1053
      patients (69.69%) were operated due to radiculopathy of herniated disc etiology,
      83 patients (5.50%) because od spondylotic radiculopathy and 38 patients (2.51%)
      because of spinal stenosis. 327 patients (21.64%) underwent surgery due to
      associated lesions, while 10 (0.66%) were operated because of other lesions. In
      patients with isolated disc herniations either interhemilaminectomy or
      extirpation of the degenerated pulp nuclei was performed, while in patients with
      spondylotic and stenotic radiculopathies most often decompressive laminectomy
      with facectomy and foraminatomy were performed. In cases of combined lesions
      combined surgical procedures were performed. There was no perioperative
      mortality. In 5 operated patients (0.33%) nonsurgical complications occurred,
      such as thrombophlebitis. Reoperation was performed in 94 patients (6.22%). Wound
      infection occurred in 4 patients (0.26%) and liquor fistula in 3 patients
      (0.20%). The paper presents diagnostic procedures, indications for surgical
      treatment and strategies.

PMID- 8999297
TI  - [Transfusion aspects of viral hepatitis C].
AB  - The investigation comprised 83 patients with acute non-A, non-B hepatitis who
      were treated at the Clinic of Infectious and Dermatovenerology Diseases in Novi
      Sad in the period 1986-1991. They were receiving blood transfusions and/or blood
      products from blood donors who had not been previously tested for presence of
      hepatitis C virus (HCV). In order to establish diagnosis anti-HCV ELISA screening
      tests from various producers were used. Out of 83 blood screening assays 17
      patients (20.48%) were found to be anti-HCV seropositive. Out of these 17
      seropositive patients 3 patients were intravenous drug-addicts (IVDA), while 14
      patients (16.68%) previously received blood transfusions, whereas out of these 7
      patients underwent open heart surgery. Only 2 blood donors, out of 48 whose blood
      was used for therapeutical purposes, were found to have anti-HCV antibodies after
      blood screening assays. The blood with detected anti-HCV antibodies caused acute
      post transfusion hepatitis C in 6 blood recipients. The obtained results show
      that comprehensive and thorough blood screening assays should be performed in all
      blood donors in order to prevent incidence of post transfusion C hepatitis. The
      Blood Transfusion Center in Novi Sad introduced compulsory viral screening assays
      for all blood donors on November 15, 1994, and since then 15019 blood donors have
      been tested. Only 38 (0.25%) were found to be anti-HCV seropositive, and were
      excluded from further blood donation and are under constant control. Now it is
      impossible to transmit HCV to patients who receive blood transfusion and/or blood
      products, and at the same time anti-HCV seropositive donors are prevented to
      develop chronic hepatitis and adverse complications due to HCV presence.

PMID- 8999298
TI  - [Photochemical oxidants in Novi Sad 1992-1995].
AB  - Nowadays photochemical oxidants present the most important problem of air
      pollution in the world, and due to this a leading cause of destroying quality of
      environmental health. Higher concentrations of ozone in urban areas of Europe are
      evident (about 1-2%) from the North to the South especially. During 1992-1995,
      from June to September, photochemical oxidants concentrations were studied (ozone
      at 4 a.m. and 4 p.m.; nitrogen dioxide at 8 a.m.; formaldehyde at 8 a.m. and
      total carbon dioxide at 8 a.m.) all factors of "Summer photochemical smog", with
      records on the number of vehicles on highways and climate data. Gathered results
      show that the health of the population is not endangered by Summer smog. Linear
      correlation data of certain pollutants with climate (temperature, atmospheric
      pressure and relative air humidity) are in accordance with data in the world.

PMID- 8999299
TI  - [Cytologic diagnosis of Hashimoto's thyroiditis].
AB  - Cytologic findings and thyroglobulin antibodies were analyzed in 46 patients with
      chronic Hashimoto's thyroiditis. Only one patient underwent surgery because of
      Hurthle adenoma, while the histopathologic diagnosis was identical to the
      cytologic. In all patients the cytologic findings revealed chronic thyroiditis,
      and in 39 patients the titer of thyroglobulin antibodies was positive or highly
      positive. In 7 patients the antibodies were slightly positive. In 11 patients a
      control punction of the thyroid gland nodule was performed as well as the control
      of antibodies. There were no changes in the cytologic findings, not even in cases
      where the titer of thyroglobulin antibodies decreased. During the four year
      period of study there was not a single case where the clinical findings pointed
      to aggravation of the disease.

PMID- 8999300
TI  - [Infiltration of the testes in acute lymphoblastic leukemia in childhood-
      personal experience].
AB  - According to various literature data testicular leukemic infiltration occurs in 5
      40%, while the mean time for testicular recurrence is 36 months. Hematologic
      recurrence usually occurs in the interval from 1-6 months. Although testicular
      leukemic infiltration clinically occurs as an isolated recurrence of leukemia, it
      usually presents only a clearly marked spot in the general recurrence of the
      disease. It is a painless enlargement of one or both testes. The diagnosis is
      made ultrasonographically and by histopathologic examination of the biopsied
      testicle tissue. This paper deals with 4 patients with acute lymphoblastic
      leukemia and testicular recurrence. In 2 patients the testicular recurrence
      occurred as a part of the general recurrence of the disease, while in the other 2
      at the time of testicular recurrence diagnosis, the bone marrow was regular. All
      4 patients were treated with combined radiotherapy and chemotherapy, in 3 cases
      successfully.

PMID- 8999301
TI  - [Evaluation of the Respiralex test for rapid isolation of Streptococcus pyogenes
      directly from throat swabs].
AB  - Results obtained by fast Respiraplex test were compared with findings of
      classical method of cultivation in order to assess possibilities of this test in
      isolation of Streptococcus pyogenes directly in the throat swab. The sensitivity
      of the fast test was 79.4%; specificity 100%. On the basis of gathered results,
      the following can be concluded: the fast test cannot completely substitute the
      classic method of cultivation although high specificity occurs, because of low
      sensitivity especially in patients with small number of colonies in the culture.

PMID- 8999302
TI  - [The functional therapy of fractures of the mandibular condyle. Our experience].
AB  - This work dealt with clinical experience since 1992, in management by functional
      therapy of mandibular condyle fractures, of the Institute of Oral and Maxillo
      Facial Surgery in the I Policlinico of Naples. In this work from 87 treated
      patients, only a group of 8 has been considered because it expresses the
      heterogeneity of all cases about the age, the sex, the kind and the level of
      fracture and the association with other fracture of the skull. The results
      obtained show that the functional therapy must be considered the first opinion in
      the mandibular condylar fractures at least there are specific conditions.

PMID- 8999303
TI  - [Calcium release from the mineral matrix of the mandibular bone due to hydrogen
      peroxide exposure].
AB  - The purpose of this paper is to quantify by in vitro experiment free radical
      activity in jaw bone demineralization processes. Sample were take and graphic
      interpolation of calcium ions undertake. The significance of the results is
      compared with the paper that are published in literature on the same subject.

PMID- 8999304
TI  - [Alcohol and smoking. The risk factors for the oral cavity].
AB  - A higher risk for the development of oral cancer was associated with heavy
      smoking and heavy drinking, but alcohol drinking and tobacco smoking are also
      correlated with other oral cavity disease. Tobacco is the most important factor
      of leukoplakia, but other diseases like ANUG, periodontitis, median rhomboid
      glossitis, chronic hyperplastic candidiasis and others are also correlated to
      cigarette smoking. It was observed that smokers have more plaque than non
      smokers, even if no difference in the bacteria composition was found between
      smokers and non-smokers samples, and the vascular reaction associated with plaque
      induced gingivitis is suppressed in smokers. Periodontitis are generally
      considered to be a consequence of an unfavourable host-parasite interaction, but
      personal factors that diminish the efficiency of the host defence, like tobacco
      smoking and alcohol drinking, can play an important role in the development of
      periodontal diseases. Cigarette smoking may be considered a major risk factor for
      periodontitis and it can also increase its severity; therefore, alveolar bone
      loss increases with tobacco smoking. Recent investigations show that smokers
      respond less favourably than no smokers to the different modalities of
      periodontal therapy, as surgical and non surgical, or guided tissue regeneration.
      Moving from these observations the authors critically analyze the literature
      concerning these important risk factors which appear to be strongly correlated
      with periodontal diseases.

PMID- 8999305
TI  - [Angiomas of the maxillofacial area: a clinical study with MR and angio-MR].
AB  - Reporting 3 cases of hemangiomas of the maxillo-facial area the authors describe,
      proper use, of RBc scintigraphy, CT with contrast media, MR, angio-MR. Comparing
      these methods it will results that RBc scintigraphy is a very useful method in a
      screening phase providing data concerning kind of blood flow, morphology of
      lesions and also detecting unknown lesions by total body scanning. CT imaging
      with contrast media is a useful method in a presurgical phase providing the exact
      anatomical limits of the lesions especially when involving bone tissue. MR
      imaging provides precise anatomic limits specially for low flow lesions; it also
      provides a vascular map of the arterial afferent vessels in high flow vascular
      lesions, without any use of ionogenic radiations. For these reasons MR is
      advisable in pediatric age and allergic patients. Super-selective embolization,
      sclerosant therapy and surgery therapy are indicated for treatment of high flow
      and low flow hemangiomas.

PMID- 8999306
TI  - [Flurbiprofen collutory in oral surgical pathology].
AB  - This study was carried out in a group of 40 patients (both sexes) aged between 18
      and 65 years old. The following pathologies were controlled and studied using
      collutory flurbiprofen: aphthous stomatitis, pressure ulcer caused by badly
      fitted mobile prostheses, radicular residue, particularly sharp and cutting
      dental cusps, pre-and postoperative treatment for the diagnosis of embedded 8th.
      The topical use of collutory flurbiprofen enabled a rapid resolution of phlogosis
      and painful symptoms to be achieved. The positive results obtained using
      collutory flurbiprofen in the aforesaid pathologies prompted the authors to
      evaluate the efficacy of the product, which is still undergoing trials, also in
      lichen ruber planus and leukoplakia.

PMID- 8999307
TI  - Hypothermia-related deaths--Vermont, October 1994-February 1996.
AB  - Hypothermia is a lowering of the core body temperature to < or = 95 F (< or = 35
      degrees C). From 1979 through 1992, a total of 10,550 persons in the United
      States died from hypothermia, an average of 754 deaths per year (range: 557-1021
      deaths). From October 1994 through February 1996, a total of 10 hypothermia
      related deaths were reported by the chief medical examiner in Vermont. The
      average age of the 10 decedents was 62 years (range: 18-88 years); eight were
      men. Seven decedents were reported to have had histories of mental illness, and
      alcohol abuse was mentioned on the police or pathology report for two decedents.
      This report summarizes the investigation of three of these deaths and describes
      risk factors commonly associated with hypothermia.

PMID- 8999308
TI  - Estimates of retailers willing to sell tobacco to minors--California, August
      September 1995 and June-July 1996.
AB  - The prevalence of tobacco use among adolescents is increasing, and the most
      common source of tobacco products for persons aged < 18 years (minors) is retail
      stores. In 1991, an estimated 29.6 million packs of cigarettes were sold
      illegally to minors in California, and an estimated 255 million packs were sold
      illegally to minors nationwide. Federal law (i.e., the Synar Amendment) enacted
      in July 1992 requires all states that receive federal funds for prevention and
      treatment of substance abuse to have and enforce laws prohibiting the sale or
      distribution of tobacco to minors, conduct annual statewide inspections of over
      the-counter tobacco outlets and vending machines to assess the statewide rate of
      illegal tobacco sales to minors, and develop a plan to decrease the illegal sales
      rate to < or = to 20% over several years. On September 28, 1994, California
      enacted the Stop Tobacco Access to Kids Enforcement (STAKE) Act, which requires
      that 1) tobacco retailers (i.e., vendors) post warning signs at each point of
      purchase and check the identification of persons who appear aged < or = to 18
      years; 2) the California Department of Health Services (CDHS) develop a statewide
      enforcement program and establish a toll-free telephone number for reporting
      observed illegal tobacco sales to minors and 3) CDHS annually assess and report
      the rate of illegal sales of tobacco products to minors. This report describes
      the retailer education and enforcement program and summarizes the results of the
      first two annual assessments (Youth Tobacco Purchase Surveys [YTPSs]). The
      findings indicate that, from August-September 1995 to June-July 1996, among over
      the-counter tobacco outlets the percentage of retailers who asked for age
      identification increased substantially, the percentage of stores displaying
      warning signs on age restrictions increased, and the percentage of retailers
      willing to sell tobacco products to minors decreased.

PMID- 8999309
TI  - Decreased antibody response to influenza vaccine among nursing-home residents who
      received recalled vaccine--New York, 1996.
AB  - Following a voluntary recall in November 1996 of 11 lots of Fluogen trivalent
      influenza vaccine (Parke-Davis Division, Warner Lambert Company, Morris Plains,
      New Jersey), the New York State Department of Health and CDC evaluated antibody
      response to the 1996-97 influenza vaccine among residents (n = 86) of three
      nursing homes who received recalled vaccine and among residents (n = 86) of three
      other nursing homes who received vaccine produced by a different manufacturer.
      The Fluogen lots were recalled because the monitored quantity of
      A/Nanchang/933/95(H3N2) hemagglutinin antigen in the 1996-97 influenza vaccine
      had declined since the vaccine initially was released; the reason for this
      decrease is unknown. The findings of this analysis indicate that, compared with
      elderly nursing-home residents who received influenza vaccine from a different
      manufacturer, residents who received Fluogen from recalled lots had moderately
      lower antibody responses to the influenza A/Nanchang/933/95(H3N2) component of
      the 1996-97 influenza vaccine.

PMID- 8999310
TI  - Update: influenza activity--United States, 1996-97 season.
AB  - In collaboration with the World Health Organization (WHO), its collaborating
      laboratories, and state and local health departments, CDC conducts surveillance
      to monitor influenza activity and to detect antigenic changes in the circulating
      strains of influenza viruses. This report summarizes influenza activity in the
      United States from September 29 through December 7, 1996, and indicates that
      influenza activity has increased since mid-November.

PMID- 8999311
TI  - [Complete oligomerization of the nucleoprotein and various strains of influenza
      virus].
AB  - Previously we demonstrated that in the course of intracellular reproduction of
      WSN influenza virus strain, part of monomeric nucleoprotein (NP) undergo
      polymerization into dimers and trimers, which dissociate into monomers after
      boiling. Further studies showed that different strains of influenza virus are
      characterized by different degree of NP-oligomerization. Specifically, Duck/
      Ukraine/63 (H3N8) and Seal Massacuhsets 1/80 (H7N7) NP monomers are completely
      transformed into oligomers. As a result of 40-min chase and of prolonged label
      exposure only NP-oligomers but not monomers can be detected in unboiled samples
      of infected cells or in virions. NP monomers of A/Duck/Ukraine strain are
      detectable in unboiled samples only after a short period of labeling. Influenza
      virus NP oligomers are more hydrophobic than NP monomers. Oligomers are
      hypothesized to be the native functionally important form of influenza virus NP.

PMID- 8999313
TI  - [Detection of the functionally active domains in the molecule of the lethal
      factor of the anthrax exotoxin].
AB  - Three functional domains were revealed in the molecule of the lethal factor of B.
      anthracis. They are located in the linear structure of the molecula as follows:
      the associative domain occupies the area from Lys39 to Met242, the stabilizing
      domain from Leu517 to Lys614, and the effector domain still further to the COOH
      terminal Lys mino acid.

PMID- 8999312
TI  - [Detection of the functionally active domains in the molecule of protective
      antigen of the anthrax exotoxin].
AB  - Using the limited proteolysis method, we established that the protective antigen
      (PA) molecule consists of four functionally active domains. The shielding domain
      occupies an area in the linear structure of the molecule PA with NH4-terminal up
      to Lys166 and plays an important role in the proteolytic activation of PA. The
      associative domain situated in the Arg167-Met266 region is responsible for
      interactions with either lethal or edematous factors in self-assembly of the
      toxic complexes of the lethal or edematous toxin. The stabilizing domain occupies
      the Gly351 to Met434 area. On the one hand, this area promotes the formation of
      conformationally stable toxic complexes with the lethal factor, on the other,
      directly participates in the formation of the hydrophobic canal, through which
      the molecule of the lethal or edematous factor and, evidently, a fragment of PA
      molecule as well (from Arg167 to Gly314), including the associative gene, gets
      inside the target cell. The receptor domain representing a COOH-terminal region,
      starting from Leu663 amino acid, interacts with the specific receptors on
      macrophages and thus delivers the toxic complex to the target cell.

PMID- 8999314
TI  - [Biosynthesis of alpha2-interferon and tumor necrosis factor at different stages
      of culturing].
AB  - Study of the biosynthesis of human alpha 2-interferon and tumor necrosis factor
      in derivatives of E. coli SG200-50 recipient strain containing pIF16, pTNF311,
      and pLT21 plasmids demonstrated elimination of the plasmids from the cells
      without degradation thereof in the course of culturing. Methods increasing the
      content of the end products in the biomass are proposed.

PMID- 8999315
TI  - [The use of synthetic peptides for detection of antibodies against foot-and-mouth
      disease virus in the blood from convalescent animals].
AB  - Peptides were synthesized, which, according to theoretical analysis of the
      antigenic structure of protein VP1 of foot-and-mouth disease (FMD) virus types A,
      0, and Asia 1, corresponded to potential immunodominant protein sites. Activities
      of the peptides were studied by solid-phase indirect radioimmunoassay on
      polyethylene film with purified immunoglobulins against intact FMD virus.
      Virtually no cross reactions were observed. Blood sera of cattle convalescent
      after FMD were tested with the FMD virus and peptides containing VP1 fragments
      141-160 (A22 No. 550), 140-160 (O1 No. 194), and 140-153 (Asia 1 No. 48). The
      specificity of interactions between the sera and peptides and the virus was
      uniform, this permitting the identification of the virus type which caused the
      disease.

PMID- 8999317
TI  - [Modification of tobacco mosaic virus envelope protein using
      trinitrobenzenesulfonic acid].
AB  - The process of modification of tobacco mosaic virus (TMV) coat protein with a
      lysine-specific reagent trinitrobenzenesulfonic acid (TNBS) was studied. TMV coat
      protein molecule is known to contain just two Lys residues (K53 and K68)
      localized in the same region of TMV coat protein subunit tertiary structure at a
      distance of about 70Ao from the virion axis. TNBS was used to modify the coat
      protein of wild type (U1) TMV and that of a coat protein ts-mutant ts21-66,
      bearing two amino-acid substitutions (I21 T and D66 G), both localized in the
      70Ao region. In the mutant coat protein, TNBS modification rate for one of the
      two Lys residues was found to increase drastically (7 to 8 times) between 30 and
      32o at pH 8.0. In U1 coat protein a similar increase was observed for one of Lys
      residues at 36o and pH 8.6. The results may indicate that the 70Ao region
      represents the labile section of TMV coat protein molecule, and gradual
      destruction of this site results first in loss of protein capacity to form well
      arranged two-cylindrical aggregates and then (after slight heating) in loss of
      capacity to form ordered helical aggregates.

PMID- 8999316
TI  - [Comparative study of the synthesis and specificity of enterotoxin from Vibrio
      cholerae O139 serotype using monoclonal antibodies].
AB  - Strains of V. cholerae serovar 0139 showed a higher intensity of multiplication
      and lesser nutritive requirements and produced 2-5 times higher amounts of
      enterotoxin during in-depth culturing than cholera vibrios of groups O1 and non
      O1. R-forms of V. cholerae were characterized by the highest production of toxin.
      Dot-immunoanalysis and immunoblotting with monoclonal antibodies demonstrated the
      identity of cholera toxin and enterotoxin of V. cholerae serovar O139. The
      authors come to a conclusion that selective efficacy of the developed vaccines
      against diarrhea caused by V. cholerae serovar O139 depends on the presence of
      homologous O-antigen in their composition.

PMID- 8999318
TI  - [Synthesis, cloning, and expression in Escherichia coli cells of human alpha1
      antitrypsin cDNA].
AB  - cDNA coding for the full-length human alpha 1-antitrypsin (AAT) and its leader
      sequence has been cloned and sequenced. DNA sequences encoding the deletion
      variants and a full-length copy of AAT were cloned and expressed under trp
      promoter control. It has been shown that guanine replacing right upstream and
      downstream the ATG of deletion variant increases the expression to ten-fold. The
      synthesis of deletion AAT in E. coli was evaluated immunologically and the level
      of the synthesis was shown to be 4-5% of total cellular protein.

PMID- 8999320
TI  - [Essays on modern molecular genetics from a lecture course for students of the
      biology department of Moscow State University. Essay 5. Transgenosis and new
      molecular genetics].

PMID- 8999319
TI  - [Cloning and sequencing of genes coding the glycoproteins of antigens A and B of
      oncogenic strain JM of Marek disease virus (MDV)].
AB  - The genes encoding the precursors of secretory glycoprotein gp57-65 (A antigen)
      and glycoprotein complex gp100, gp60, gp48 (B antigen) of virulent strain JM of
      Marek's disease virus (MDV) have been cloned using PCR of viral DNA. Nucleotide
      sequences of both genes have been determined and amino acid sequence of the
      precursor peptides predicted, and compared with the corresponding sequences of
      other MDV strains. The results will be used for developing methods for the
      diagnosis of Marek's disease and vaccination against it.

PMID- 8999321
TI  - [Optimization of Brucella detection using polymerase chain reaction].
AB  - The possibility of using polymerase chain reaction (PCR) for the laboratory
      diagnosis of brucellosis was tested with a representative regional collection of
      44 Brucella strains. The strains differed by the test and source of isolation,
      virulence, and phenotypical characteristics. Optimal parameters of PCR have been
      defined and the possibility of detecting the agents in pathological material from
      cattle demonstrated.

PMID- 8999322
TI  - [A novel method of concentrating bacterial suspensions for transmission electron
      microscopy].
AB  - Presents a new method for making preparations of bacteria and their unculturable
      forms from suspensions with low concentrations of cells, from 1 x 108 to 1 x 104
      per ml. to be examined under transmission electron microscope. The novelty of the
      method consists in the technique of concentrating bacteria by making a colloid
      solution consisting of bovine serum albumin and polyethyleneglycol. Associations
      of protein molecules, polyethyleneglycol, and bacteria, forming in the solution,
      are sedimented by centrifugation after 48-hour incubation at 4 degrees C. The
      solidity of the resultant macroscopic sediment is sufficient for studying the
      cells contained in it under transmission electron microscope.

PMID- 8999323
TI  - Pitfalls of genetic testing.

PMID- 8999324
TI  - Pitfalls of genetic testing.

PMID- 8999325
TI  - Pitfalls of genetic testing.

PMID- 8999326
TI  - Absence of HHV-8 in prostate and semen.

PMID- 8999327
TI  - Absence of HHV-8 in prostate and semen.

PMID- 8999328
TI  - More on pravastatin and coronary disease.

PMID- 8999329
TI  - Sequencing of chemotherapy and radiotherapy in breast cancer.

PMID- 8999330
TI  - Sympathetic-nerve activity before and after resection of an insulinoma.

PMID- 8999331
TI  - Inherited metabolic myopathy and hemolysis due to a mutation in aldolase A.

PMID- 8999332
TI  - The politics of human-embryo research.

PMID- 8999333
TI  - The politics of human-embryo research.

PMID- 8999334
TI  - Epidemiology of Inhalant Abuse: An International Perspective. Proceedings of a
      meeting. July 21-22, 1993.

PMID- 8999335
TI  - [Mining in the Harz Mountains in the times thereafter and its effects on the
      environment].
AB  - Not only during the industrial age have mining and metallurgy strongly influenced
      environmental developments. Since the beginning of mining activities and smelting
      ores, parts of the processed minerals, especially various heavy metals, have been
      lost during various technical operations and been distributed by water and wind
      over large areas. A good example for the Middle Ages and thereafter was the
      silver, lead, and copper mining district of the Harz Mountains in northeastern
      Germany. Environmental problems caused by the activity in this mining center have
      been known since the Renaissance. The rivers transported sand-like lead minerals
      over long distances, which were distributed over large areas by floods,
      especially in spring when the snow melted. The lead got into the food of various
      farm animals and poisoned them, as we know from the complaints of inhabitants of
      the area to the authorities particularly during the 17th-19th centuries. These
      environmental problems have been the subject of scientific studies as early as
      the first half of the 19th century.

PMID- 8999337
TI  - Managed care and the nephrologist: subject of one-day symposium.

PMID- 8999338
TI  - Patient selection and the success of peritoneal dialysis.

PMID- 8999336
TI  - [Polymer-supported synthesis of biopolymers--foundations and applications].
AB  - The application of polymer supports for the synthesis of polypeptides,
      oligonucleotides, and oligosaccharides is presented in this article and discussed
      in view of their methodology. The fundamentals of the polymer-supported synthesis
      are described as well as the role of the polymer supports in the synthetic cycle,
      and the problems associated are debated. It is focused on typical polymer
      supports for each substance class, and an overview is given on recent tendencies
      of development in the polymer-supported methods of synthesis.

PMID- 8999339
TI  - Travelling with ESRD. Protecting the dialysis prescription during travel.

PMID- 8999340
TI  - Increase in capitated payment first step in improving reimbursement picture:
      practice expenses are next hurdle.

PMID- 8999341
TI  - [Patients with a borderline disorder in the health care system].

PMID- 8999342
TI  - [Infection with Helicobacter pylori, the end in sight?].

PMID- 8999343
TI  - [Pathophysiology and treatment of achalasia].

PMID- 8999344
TI  - [Methyl thionine (methylene blue) in the treatment of sepsis].

PMID- 8999345
TI  - [Clinical judgment and decision making in clinical practice. A patients with 'the
      flu'].

PMID- 8999346
TI  - [Transjugular intrahepatic portosystemic shunt in the treatment of refractory
      ascites in 21 patients].
AB  - OBJECTIVE: To determine the value of the transjugular intrahepatic portosystemic
      stent shunt (TIPS) in the treatment of patients with cirrhosis and refractory
      ascites. DESIGN: Descriptive follow-up study. SETTING: University Hospital
      Gasthuisberg, Leuven, Belgium. METHODS: In a period of three years, 21
      consecutive patients with cirrhosis and refractory ascites were treated with
      TIPS. Refractory ascites was defined as ascites resistant to maximum diuretic
      therapy and repeated paracentesis. The mean follow-up was 9 months (range 3-26).
      RESULTS: Creation of the stent shunt was technically successful in 20 patients
      and resulted in a decrease of the pressure gradient between the portal vein and
      the inferior vena cava by approximately 47%. The procedure was immediately lethal
      in two patients. Complications occurred later on in four patients: thrombosis of
      the stent in 3 patients and disabling encephalopathy in one. Five other patients
      died from liver failure, four of them possibly related to the increase of the
      portosystemic shunting. The stent shunt had no ill effects on kidney function.
      Thirteen patients were still alive at the end of follow-up. Five patients (24%)
      had a total and sustained remission of the ascites. Seven patients (33%) still
      had ascites but needed no paracentesis. One patient did not respond to the
      treatment. The best results were observed in 14 alcoholics: 9 (64%) responded
      favourably (43% in non-alcoholics), in 4 of these the ascites had disappeared.
      CONCLUSIONS: TIPS placement needs substantial experience to avoid technical
      complications. In case of refractory ascites, only patients for whom later liver
      transplantation is considered should be submitted to the procedure, because TIPS
      placement can lead to deterioration of liver function.

PMID- 8999347
TI  - [Implementation of guidelines for clinical practice in a surgical department].
AB  - OBJECTIVE: To evaluate implementation of clinical practice guidelines. DESIGN:
      Prospective evaluation study. SETTING: Department of Surgery. Academic Medical
      Center. University of Amsterdam, the Netherlands. METHODS: Clinical practice
      guidelines on patient care were developed by physicians working in the department
      of surgery. Six months after their introduction a selected, representative group
      of consecutive patients, admitted during 4 months, was followed by an independent
      investigator who determined compliance with a large number of guidelines. After
      this study period all physicians of the department were given oral and written
      feedback. This was followed by a period of two months during which compliance was
      determined again. RESULTS: In the first study period 226 patients were included.
      Compliance with most of the guidelines evaluated was over 70%. Compliance with
      the guidelines described in this article (antibiotic and thrombosis prophylaxis,
      use of urinary tract catheters and wound drains, diagnostics and therapy in
      symptomatic gallstones and distal obstruction icterus) ranged from 49% for the
      use of urinary tract catheters to 94% for thrombosis prophylaxis. In the second
      study period 106 patients were studied and no differences in compliance were
      found, except for the use of urinary tract catheters (from 49% to 73%).
      CONCLUSION: This study demonstrates that it is possible to introduce clinical
      practice guidelines in a surgical ward successfully and to reduce variation in
      patient care. Providing aggregated feedback is not sufficient to improve
      compliance with guidelines.

PMID- 8999348
TI  - [Home visits by community health nurses can contribute to the family
      practitioner's knowledge of elderly patients].
AB  - OBJECTIVE: To determine to what extent the general practitioner (GP) is aware of
      the health status and functioning of his elderly patients and in which areas this
      knowledge can be completed with the aid of community nurses. DESIGN: Cross
      sectional, descriptive. SETTING: Department of General Practice. State University
      Limburg, Maastricht, the Netherlands. METHODS: A random sample of 59 patients
      aged 79 years and over, belonging to the population of a primary health care
      centre, were visited by community nurses. One patient was lost. The nurses
      inventoried the patients health complaints and their daily functioning by means
      of a structured questionnaire. Data from these home visits were compared with
      data from the same questionnaire, regarding the same patients, which the three
      GPs of the health centre had filled in on the basis of their medical records.
      RESULTS: Of the complaints recorded by the community nurses. 34% were not known
      to the general practitioners. This concerned mainly symptoms of depression,
      urinary incontinence, disabilities and handicaps of the musculoskeletal system.
      sleep disturbances, daily functioning and ability to cope. The main determinants
      of the ability to cope were impaired walking and to a lesser degree symptoms of
      depression. CONCLUSION: A structured interview of elderly patients by a community
      nurse yields substantial information about health problems.

PMID- 8999349
TI  - [Colonic varices: an unusual cause of occult blood loss].
AB  - A man aged 81 known to suffer from atrial fibrillation - the treatment for which
      included acetylsalicylic acid - and chronic obstructive pulmonary disease, was
      hospitalized because of a respiratory infection. Since he had iron deficiency
      anaemia and the case history mentioned "intestinal bleeding', supplementary
      examinations were carried out. Endoscopy revealed colonic varices; because of the
      absence of portal hypertension and other disorders related to colonic varices,
      the varices were classified as idiopathic. In view of the extensiveness of the
      lesions, it was decided to refrain from endoscopic sclerotherapy and to adopt an
      expectative policy.

PMID- 8999350
TI  - [Current viewpoints on diagnosis and treatment of Helicobacter pylori
      infections].

PMID- 8999351
TI  - [Acquired non-scrotal testis in boys: an underestimated phenomenon].

PMID- 8999352
TI  - [Prenatal studies of trisomy 21: triple test more efficient than age criterion].

PMID- 8999353
TI  - [The role of health care in occupational disability].

PMID- 8999354
TI  - [Wrong beds and wrong care].

PMID- 8999355
TI  - [Various viewpoints of family physicians and rheumatologists on care of patients
      with rheumatoid arthritis].

PMID- 8999356
TI  - [Echography in the diagnosis of dysplastic hip development].

PMID- 8999357
TI  - [Ethical aspects of cost considerations in medical decision making].

PMID- 8999358
TI  - Combined cardiovascular risk factor intervention: a bridge between primary and
      secondary prevention?

PMID- 8999359
TI  - Hepatitis in a patient with SLE: is it autoimmune hepatitis?
AB  - In a patient with systemic lupus erythematosus (SLE), we considered the diagnosis
      of autoimmune hepatitis (AIH) in view of raised serum aminotransferases,
      hypergammaglobulinaemia, antinuclear antibodies (titre 1:10,240), seronegativity
      of markers for viral hepatitis and absence of recent hepatotoxic drug usage. The
      diagnosis of AIH was supported by using the scoring system, recently developed by
      the International Autoimmune Hepatitis Group and the excellent response to
      treatment with prednisone. Liver histology, however, showed no characteristic
      features of AIH. The relevance of liver histology and scoring for AIH in SLE with
      hepatic involvement is discussed.

PMID- 8999360
TI  - The spectrum of chronic mature T-cell disorders: a report of four cases.
AB  - We describe four patients with a mature T-cell disorder. These four specific
      entities belong to a group formerly called "T-cell chronic lymphocytic leukaemia"
      (T-CLL). Nowadays we understand that these chronic T-cell lymphoproliferative
      disorders consist of four different entities. They stand out as well-described
      and separate disorders on the basis of their clinical, immunophenotypic and
      cytogenetic properties. Unfortunately, the majority of patients have a bad
      response to chemotherapy. The purine analogs may offer a better prognosis for
      some patients.

PMID- 8999361
TI  - From compliance to alliance. A quarter century of research.

PMID- 8999363
TI  - Transient bilateral cortical blindness as a presenting symptom of infective
      endocarditis.

PMID- 8999362
TI  - Smoking and diabetes mellitus.
AB  - The goal of this review is to determine the effects of smoking on diabetes
      mellitus, whether it aggravates diabetic complications or influences insulin
      metabolism and action. Also available anti-smoking programmes applicable for
      diabetic patients have been studied. The prevalence of smoking among diabetic
      patients has been investigated by conducting a meta-analysis. Compared with
      normal subjects, the prevalence of smoking among diabetic patients is
      significantly higher (27 vs. 33%, p < 0.0001), IDDM patients largely accounting
      for this difference. However, care must be used in interpreting these data.
      Smoking presents an extra risk for development of macro- and microvascular
      complications in these patients, contributing to increased cardiovascular
      morbidity and mortality. Smoking also increases the risk of diabetes itself.
      Neither acute nor habitual smoking causes substantial changes in insulin
      sensitivity in IDDM patients, whereas it does so in NIDDM. Studies in diabetic
      patients concerning anti-smoking strategies are scarce and only yield
      disappointing results. Making these patients abstain from smoking turns out to be
      extremely difficult, probably due to the considerable psychosocial stress
      experienced.

PMID- 8999365
TI  - [Monoplane, biplane and multiplane transesophageal echocardiography. Indications,
      contraindications, complications and examination technique].
AB  - Major clinical applications and examination technique of transesophageal
      echocardiography are described on the basis of personal experience and literature
      data. Capabilities of monoplane and more recent biplane and multiplane
      transducers are discussed. Transesophageal examination appears to be
      complementary to transthoracic technique; it is also utilized in the preoperative
      and intraoperative monitoring of surgical procedures and during interventional
      catheterization. The clinical indications for transesophageal echocardiography
      include aortic dissection, dysfunction of valvar prosthesis, detection of an
      intracardiac source of embolism, assessment of infective endocarditis, congenital
      and valvular heart disease, and evaluation of cardiac masses. Another application
      is the assessment of cardiovascular function of critically ill patients in the
      coronary, medical, or surgical intensive care unit, due to limited transthoracic
      echocardiographic acoustic windows. When performing a transesophageal
      examination, a methodical approach is preferred consisting of a sequence of
      transducer positions and views. With each successive advance in transducer
      technology the number of available imaging planes has increased. The monoplane
      device can optimally image only two primary planes of the heart, i.e. short-axis
      and frontal planes. The biplane probe adds substantially more diagnostic
      information over a monoplane transducer because of a second imaging array in the
      longitudinal orientation. The multiplane device produces a continuum of
      transverse and longitudinal images by rotation of the electronic array and more
      readily provides intermediate and off-axis images between the primary planes.

PMID- 8999364
TI  - [Combined use of bicycle ergometry test and echo-dipyridamole in stratification
      of risk after thrombolysed myocardial infarct].
AB  - AIM: Verify the value of the combined use of Dipyridamole Stress Echocardiography
      (DSE) and Exercise Testing (ET) for predicting cardiac events after Thrombolysed
      Myocardial Infarction (TMI). STUDY DESIGN: Prospective, with a medium follow-up
      of 221 days (range 30-446). CLINICAL SETTINGS: Coronary Care Unit with Cardiology
      Service. PATIENTS: 32 consecutive patients, 24 men and 8 women, mean age 61 years
      (range 39-72) with acute myocardial infarction. INTERVENTIONS: Systemic
      thrombolysis with PTPA. DSE and ET in therapeutic wash out 12 +/- 3 days after
      admission to the Coronary Care Unit. RESULTS: 9 patients had positive ET, 18
      patients had negative ET, 5 patients did not perform ET. 19 patients had positive
      DSE, 13 patients had negative DSE. Patients with positive DSE had in 6 cases
      (group 1) WMA remote from the infarction area (WMAR), in 13 cases (group 2) WMA
      appeared in the infarct related area. Cardiac events occurred in 15 patients: 1
      cardiovascular death, 1 myocardial re-infarction, 13 cases of unstable angina. 2
      patients with negative DSE had cardiac events. All patients in group 1 had
      events, 1 patient with a previous positive ET, 3 patients with previous negative
      ET. 2 patients in this group didn't perform ET. 7 patients in group 2 had cardiac
      events, in all cases with a previous positive ET. 1 single patient in this group
      with negative ET had events. CONCLUSIONS: 1) Patients without WMA at DSE are at
      low risk for cardiac events after thrombolysed myocardial infarction. 2) Presence
      of WMAR appears to be associated with a higher risk, whatever the result of ET
      may be. 3) Patients without WMAR can be further stratified by ET in therapeutic
      wash out. High risk patients seem to be those with positive DSE and positive ET.
      4) Combined use of DSE and ET seem to allow optimal risk stratification after
      thrombolysed myocardial infarction.

PMID- 8999366
TI  - [Myocarditis in legionellosis. A case report].
AB  - Cardiac involvement during Legionnaires' disease has been rarely described; few
      cases of myocarditis, pericarditis and endocarditis were reported. We describe a
      case of myocarditis associated to pneumonia, with high antibody title suggesting
      a disease due to Legionella pneumophila. The patient had severe myocardial
      damage, with overt heart failure and important ECG and Doppler-echocardiographic
      abnormalities, without associated multiorgan involvement.

PMID- 8999367
TI  - [Arteriosclerotic aneurysms of the subclavian artery].
AB  - OBJECTIVE: To evaluate diagnostic investigations, operative management and long
      term outcome of atherosclerotic aneurysms of the subclavian artery. DESIGN: A
      retrospective clinical study through a follow-up period of 68 months (8 months to
      11 years). SETTING: Department of Vascular Surgery, University Hospital.
      PATIENTS: Between 1983 and 1995, 5 patients with atherosclerotic aneurysms of the
      extrathoracic subclavian artery were reviewed. All patients presented a pulsatile
      supraclavicular mass. Ultrasonography and angiography confirmed the diagnosis and
      were useful in planning the operation. INTERVENTIONS: Four patients were
      submitted, through a supraclavicular incision, to resection of the aneurysm and
      replacement of a prosthetic graft (dacron in 2 cases, PTFE in the remaining 2
      cases). In one patient, with a small saccular aneurysm, a tangential
      aneurysmectomy with a patch angioplasty (PTFE) was performed. RESULTS: All
      patients recovered after a mean hospital-stay of 9 days and had a valid radial
      pulsation. During the follow-up period, a dacron graft failure occurred 38 months
      later in one patient: she remains today asymptomatic. CONCLUSIONS: Resection is
      today recommended for all patients with diagnosed subclavian artery aneurysms.
      Because of unknown natural history of asymptomatic aneurysms, with an
      unpredictable risk of complications, more accurate evaluations are required for
      optimal clinical decision making (early surgery vs watchful waiting?).

PMID- 8999368
TI  - [Aneurysms of the popliteal artery. Our experience apropos of 37 cases].
AB  - The authors describe their experience concerning the surgical treatment of
      aneurysmatic pathology of the popliteal artery. This is the most frequent site
      for aneurysm after aortic aneurysm. Since 1979 to 1994, 26 patients, 21 men and 5
      women (mean age 65.8 years), have been treated at the Institute of Clinical
      Surgery of the University of Ferrara for a total of 37 popliteal aneurysms.
      Thirteen patients had more than one aneurysm. Before the operation, all patients
      underwent DSA, and echo Doppler, 7 with CAT and 4 with RMN. Twenty-nine
      substitutions, 7 by passes and 1 ligation were performed. Twelve of the 29
      substitutions were made by reversed saphenous vein. Fourteen by PTFEe, and 3 by
      dacron. In 4 cases it was necessary to reimplant either the anterior tibial
      artery (3 cases) or the posterior tibial artery (1 case) separately. The results
      obtained were good especially in the post-trauma patients. Only 3 amputations
      were necessary due to graft obstruction immediately after surgery, and in post
      traumatic conditions.

PMID- 8999369
TI  - [Contribution of a combination of alpha and beta benzopyrones, flavonoids and
      natural terpenes in the treatment of lymphedema of the lower limbs at the 2d
      stage of the surgical classification].
AB  - HYPOTHESIS: To create a phlebolymphologic therapy in order: to activate venous
      system; to activate lymphatic system; to activate macrophagic system; to reduce
      the proteic lymphatic load. EXPERIMENTAL: A study was performed on the use of an
      ideal phlebolymphological association (Tonka Beans, Gingko Biloba, Melilotus
      Officinalis) as a practical standpoint in the treatment of lymphedema of lower
      limbs in order to create an efficacious dose of Coumarin, Benzopyrones and
      Ginkolidi. CLINICAL: We investigated a population of 76 patients treated in an
      open-label study for six-eight months with a dosage of Coumarin 60 mg/daily +
      Gingko Biloba 40 mg/daily + Melilotus 40 mg/daily. CONCLUSION: This trilogy
      induced a very significant improvement in lymphedema (centimeter-aspect) both in
      functional symptoms (pain heaviness in affected limbs) and physical signs (edema,
      episodes of infection). Tolerance of long term treatment was good and the
      improvement was observed from the third month of treatment.

PMID- 8999370
TI  - [Introduction of definite molecular weight heparan sulfate in a protocol of
      prevention of deep venous thrombosis in prosthetic orthopedic surgery].
AB  - Use of definite molecular weight heparan sulphate in a protocol for the
      prevention of deep venous thrombosis in the total joint replacement surgery. The
      authors propose a working protocol for the prevention of deep venous thrombosis
      in prosthetic orthopaedic surgery. It requires that integration of
      pharmacological, anaesthesiological, rheological and physiokinesitherapic
      measures, it has permitted a very good prevention of thromboembolic disease and
      it is well-tolerated and safe. The protocol requires: peripheral anaesthesia (sub
      arachnoidal block), pre and post-operative pharmacological treatment with heparan
      sulphate of a fixed molecular weight, haemodilution with maintenance of the
      haematocrit at no more than 30%, early physiokinesitherapy associated with the
      use of elastic stockings graduated tension. The fifty patients treated with this
      protocol were controlled during the pre-operative and post-operative stage and
      one month later and no thrombo-embolic complications resulted.

PMID- 8999372
TI  - [Intensive care unit infections].

PMID- 8999371
TI  - [Use of autotransfusion in prosthetic surgery of the abdominal aorta].
AB  - Self-transfusion represents a method used for the restoration of haematic losses
      that, in recent years, has been employed more and more widely in the surgical
      ambit. The utilisation of this method has become increasingly frequent because of
      the high diffusion of blood transmitted diseases and of the incidence, not
      negligible, of complications relative to the transfusions of homologous blood.
      The techniques that are currently used are: self-donation with predeposit; inter
      surgery recovery; hemodilution normal blood volume. The authors report their
      experience relative to the use of self-transfusion, as self-donation with
      predeposit and as inter-surgery recovery, employed in the treatment of
      haemorrhagic complications, from 1990 until now in the Department of I Surgical
      Clinic of University of Turin, in a series of 48 patients in which were performed
      infrarenal abdominal aortic repair. In practice this technique did not present
      any complications.

PMID- 8999373
TI  - [Effects of PEEP on intrathoracic and extrathoracic blood volumes evaluated with
      the COLD system in patients with acute respiratory failure. Preliminary study].
AB  - AIM OF THE STUDY: To evaluate the effects of positive end expiratory pressure
      (PEEP) on intrathoracic and extrathoracic blood volumes in patients with acute
      respiratory failure (ARF). METHODS: In 4 ARF patients, we have measured cardiac
      output (CI), intrathoracic blood volume (ITBVI), global end-diastolic ventricular
      volume (GEDVI), pulmonary (PBVI) and total (TBVI) blood volumes, during
      application of two PEEP levels (0 and 10 cm H2O). These measurements have been
      performed by PULSION COLD Z-021 system, using the double indicator dilution
      technique (thermal and dye dilution). RESULTS: PEEP application caused a
      significant reduction in CI (from 3.8 +/- 0.4 to 2.9 +/- 0.1 1/min/m2) and ITBVI
      (from 888 +/- 48 to 698 +/- 25 ml/m2). The reduction in intrathoracic blood
      volume was associated with a significant reduction in GEDVI and PBVI. After PEEP
      application, there was a significant reduction in TBVI (from 2437 +/- 135 to 1984
      +/- 49 ml/m2). CONCLUSIONS: PEEP application decreases cardiac index, mainly
      through a preload reduction, as evidenced by the reduction in intrathoracic and
      end-diastolic ventricular blood volumes. The preload effect is due to an increase
      in intrathoracic pressure with reduction in total circulating blood volume. TBVI
      reduction is consistent with blood pooling in vascular compartments, e.g.,
      splanchnic compartment, characterized by long vascular time constant.

PMID- 8999374
TI  - [Prediction of outcome in critically ill patients using haemodynamic and
      oxyphoretic parameters].
AB  - OBJECTIVE: To find a predictive model for short time mortality and survival of
      haemodinamically instable patients. DESIGN: Prospective study on two consecutive
      series of critically ill patients admitted to ICU. SUBJECTS: 115 critically ill
      patients, subdivided in two series of 83 (47 survivors and 36 non survivors after
      20 days from admission) and 32 patients (19 survivors and 13 non survivors),
      respectively. INTERVENTIONTS: All the patients have been monitored with a Swan
      Ganz catheter. MEASUREMENTS: Oxyphoretic parameters were measured at 7 different
      times (T): T0 (start), T1 (after 12 hours from T0, T2 (24 hrs), T3 (48 hrs), T4
      (72 hrs), T5 (96 hrs) and T6 (120 hrs). A total number of 401 recorded values of
      the first patients' series were used to create the predictive model for outcome
      (0 non survivors, 1 survivors). Stepwise logistic regression was used to create
      the model. Model calibration and discrimination was assessed. The model was
      validated using data collected from the second series. RESULTS: The probability
      of survival after 20 days was Pr (survive) = e(logit)/1+e(logit), with "logit" = 
      5,106+(-6,58E-02 SVI)+(-2,76E-03 SVR)+(0,1379 LVSWI)+(0,8933 Hb)+(-3,25E-02
      VO2I)+(9,09E-02 O2ER)+(-7,89E-02 SHUNT)+PAT. For medical patients PAT = -0.568;
      for surgical patients PAT = -1.0525 and for politrauma PAT = 1.593. Goodness-of
      fit test showed a good calibration: chi 2 = 4.267, p = 0.832. The area under the
      ROC curve was 0.831. The model used in the validation data set, with 199 recorded
      values, also showed a good calibration and discrimination (Goodness-of-fit test:
      chi 2 = 15.65, p = 0.111; area under the curve 0.798). CONCLUSIONS: The
      mathematical model we found has been validated also in the second series and the
      discrimination capability increases with time. Using this model we can evaluate
      the probability of survival at every time. Its application at different times
      permits a better evaluation of haemodynamically instable patient trend.

PMID- 8999375
TI  - [Propofol in coronary diseases. Haemodynamic evaluation of some anesthetic
      regimes].
AB  - The haemodynamic effect of two regimens of propofol-fentanyl anaesthesia versus a
      standard isoflurane-fentanyl anaesthesia were compared perioperatively in 30
      patients with good left ventricular function undergoing coronary artery bypass
      grafting. Anaesthesia was induced in all patients with fentanyl 14 micrograms/kg,
      pancuronium 0.1 mg/kg, and thiopental 1 mg/kg. Anaesthesia was maintained: in 10
      patients with a constant propofol infusion of 200 micrograms/kg/min during the
      pre-bypass period and fentanyl boluses of 1 mg when required (PH Group); in 10
      patients with a variable propofol infusion (from 43.09 to 22.42
      micrograms/kg/min) during the pre-bypass period and a fixed infusion of 10.47
      micrograms/kg/min during the post-bypass period (PL group) in 10 patients with a
      1% isoflurane administration throughout the intraoperative period (F Group). The
      analgesia in the PL and F Groups was obtained with a fentanyl infusion of 0.3
      microgram/kg/min during the prebypass period, 0.11 microgram/kg/min during the
      postbypass period. PL Group patients received 0.06 microgram/kg/min of fentanyl
      during the first three hours of the intensive care unit (TI) stay. The PL Group
      showed a significant better haemodynamic control of oxygen consumption indexes;
      PH Group patients had a major myocardial depression, routinely requiring the use
      of cardiokinetic agents in the post-bypass period. Intraoperative opioid
      consumption was similar in all Groups whereas the F Group showed a significantly
      higher fentanyl requirement during the TI period.

PMID- 8999377
TI  - [Tourniquet pain: anatomic-physiological notes and clinical aspects].
AB  - OBJECTIVES: The mechanism of tourniquet pain is quite complex. This paper,
      supported by the previous literature on this topic, tries to explain why the
      anaesthetic blockade of a limb, even when thechnically successful, not always
      prevents the occurrence of this pain. DATA SOURCES: Papers published between 1990
      and 1995, listed on Index Medicus, with pertinent references. STUDY SELECTION:
      Reports dealing with physiological basis of tourniquet pain. CONCLUSIONS:
      Tourniquet pain is nociceptive, generated not only by activation of peripheral
      nociceptors, but also by direct axonal stimulation of nervous trunks. Is is
      hardly to tolerated by patients since ischemia and mechanical compression induce
      an activation of C fibres, resistent to ischemia. A beta fibres are involved as
      well, due to the activation of low-threshold mechanoceptors.

PMID- 8999376
TI  - [Difficult intubation in paediatric cardiac surgery. Significance of age.
      Association with Down's syndrome].
AB  - OBJECTIVE: To assess the relationship between the age of pediatric patients and
      the likelihood of difficult intubations and to confirm the importance of Down
      Syndrome causing difficult intubations. DESIGN: Retrospective study. SETTING:
      Pediatric cardiac surgery operating room. PATIENTS: 627 pediatric patients,
      suffering from congenital heart disease, operated in our hospital from 1992 to
      1994, divided in three age groups (under 1 month, between 1 month and 1 year,
      over 1 year of age). INTERVENTIONS: Translaryngeal intubation performed in the
      operating room before the operation. MEASUREMENTS: The percentage of difficult
      intubations was assessed in the three age groups and the association with Down
      syndrome was also considered. The likelihood of orotracheal intubations in each
      of the preceding groups was also examined. CONCLUSIONS: The percentage of
      difficult intubation in our experience was estimated to be 4.62%. Intubation's
      difficulty increases with decreasing age of non Down patients. The risk of
      difficult intubation in Down patients is, irrespectively of age, nearly 27%
      higher than in non-Downs (5.77% versus 4.52). However Down Syndrome seems to be
      important only in the age group between one month and one year. The percentage of
      orotracheal intubations in the preceding groups, even if indirectly, seem to
      confirm this observation.

PMID- 8999378
TI  - [Hypothyroidism and megacolon].
AB  - A 71 years old woman, affected by ischemic heart disease from the age of 50 and
      by chronic constipation was admitted to the emergency department for drowsiness,
      intense dyspnea and acute abdominal distension. Laparotomy evidenced a megacolon.
      Because of the age and sex of the patient the congenital form of the megacolon
      was ruled out. No one of the more common causes of megacolon was recognized, but
      a severe hypothyroldism and Hashimoto's thyroiditis was discovered. Treatment
      with levothyroxine caused a progressive improvement of the general condition of
      the patient and of the megacolon so that the authors hypothesize that the
      intestinal pseudo-occlusion was caused by the hypothyroidism. In this paper the
      authors make a thorough analysis of the literature about the association between
      hypothyroidism and megacolon. Although many hypothesis have been put forward
      about the possible pathogenetic association between these two diseases, until now
      no definitive result has been reached. The authors, moreover, hypothesize that
      the pleural and pericardial effusion and the peculiar metabolic state
      characterized by plasma hyponatremia and hyposmolarity, with a constant urinary
      hyperosmolarity, were also caused by hypothyroidism; in fact the clinical and
      metabolic conditions improved after levothyroxine therapy. In the end the authors
      discuss if it is preferable to use tetraiodothyronine or triIodothyronine for the
      treatment of intense hypothyroidism in a patient in critical clinical state.

PMID- 8999380
TI  - [Combination of beta-interferon and laser-CO2 therapy in female HPV genitalis].
AB  - 230 women affected by HPV genital infection diagnosed by macroscopic examination,
      colposcopy and Pap test, were divided into two groups, of 95 and 135 people
      respectively, homogeneous for lesion localization and extension. The first group
      was treated with laser CO2 and the second group was treated with laser CO2 and
      intramuscular beta-interferon. We evaluated the side effects, the clinical
      results and the incidence of recurrences after 1, 6 and 12 months after the
      complete destruction of the lesions. At the first control, in both groups, we
      found no persistence of the lesions. At the second control after 6 months
      recurrences were present in 19 patients of the first group and in 7 patients of
      the second group. 51 recurrences were present after 12 months in the first group
      and 14 in the second group. The difference, evaluated with the chi 2 test, was
      found to be statistically significant (p < 0.01 after 6 months and p < 0.001
      after 12 months).

PMID- 8999379
TI  - [Pregnancy after surgical therapy of obesity. Bibliographic review and our
      experience with biliopancreatic diversion].
AB  - BACKGROUND: An increasing number of women in childbearing age are submitted to
      surgical treatment of obesity; for this reason pregnancy represents a frequent
      event in operated patients. METHODS: In this study pregnancy in patients with
      morbid obesity submitted to jejunoileal bypass (JIB) and gastric bypass (GB) are
      reviewed from the literature and the analysis of our experience with
      biliopancreatic diversion (BPD) is reported. RESULTS: In 113 pregnancies after
      JIB reviewed from the literature, the results seem to be debated either about the
      course of pregnancy or about maternal and neonatal status. The data of literature
      concerning the pregnancies following GB are less debated but rather slight. One
      hundred and fifty-two pregnancies after BPD have a complete documentation
      concerning maternal conditions, modality of outcome and neonatal situation.
      CONCLUSIONS: Pregnancy occurred in the obese women represents an increased
      maternal-fetal risk. The excess weight loss, the weight maintenance and the
      reduced weight changes during pregnancy are an advantage in the operate women
      who, in any case, need accurate controls of the nutritional status during the
      whole gestational period. Keeping these cautions pregnancy following surgical
      treatment of obesity represents an event not only possible but even with less
      problems than in pregnancy in obese women.

PMID- 8999382
TI  - [Forceps delivery and long term follow-up urinary incontinence].
AB  - 553 patients undergoing complete urodynamic evaluation were investigated
      concerning mode of delivery. Forceps delivery was not associated with worsened
      urethral competence and significant risk of subsequent incontinence.

PMID- 8999381
TI  - [Efficacy of estrogen-progestin replacement therapy after bone marrow
      transplantation].
AB  - Ovarian failure is a common consequence of chemotherapy and radiotherapy in women
      undergoing bone marrow transplantation. The longer survival in these women has
      raised, during the past years, the need for a better quality of life. The
      objective of the present study has been to evaluate perspectively the potential
      benefit of hormonal replacement therapy in 24 women who underwent bone marrow
      transplantation. The data obtained indicated that hormonal replacement therapy
      results effective in preventing and/or relieving the multiple manifestations of
      gonadal failure, including amenorrhea, hot flashes, atrophy of genital apparatus,
      osteoporosis and cardiovascular disease.

PMID- 8999383
TI  - [Contraception and voluntary termination of pregnancy. Survey of a sample of 500
      women].
AB  - In order to better evaluate the link between contraceptive attitudes and induced
      abortion, 500 women who underwent voluntary termination of pregnancy (VTP) at the
      First Institute of Obstetrics and Gynaecology of the University of Rome "La
      Sapienza" were interviewed. They were young (median age 28 years), medium to high
      educated (61%), non married (52.4%), nulliparous (59.2%) women. Forty-two percent
      of them had the first sexual intercourse before 18 years of age and 72.6% at
      least five years before. Ninety-five women (19%) admitted a previous voluntary
      termination of pregnancy. Withdrawal (305 women), oral contraceptives (246 women)
      and condom (223 women) were the most widely used methods of fertility regulation,
      but the pill had been taken only for short periods of time, never exceeding one
      year. Withdrawal resulted to be the most utilized method during the cycle in
      which conception occurred (49.4%); no method had been employed by 34.8% of the
      women. The diffusion of modern methods of fertility regulation greatly influences
      the number of induced abortions in Italy, as clearly indicated by the progressive
      reduction of VIP starting from 1982 paralleled by a constant increase in OCs
      diffusion. Our data, although limited in number, confirm that induced abortion is
      the consequence of an insufficient use of modern methods of fertility regulation.

PMID- 8999384
TI  - [Cytogenic characterization of chromosome markers detected at amniocentesis:
      implications for karyotype-phenotype correlations].
AB  - The detection of marker chromosomes at prenatal diagnosis raises serious concerns
      regarding the phenotypic consequences on the fetus. Traditionally the classical
      approach to the problem relied upon the cytogenetic analysis of the marker
      chromosome by different banding techniques to ascertain its euchromatic content.
      This indirect methodology doesn't allow to trace the origin of the marker and to
      properly narrow the molecular boundaries of the euchromatic region. FISH
      technology by means of DNA probes regionally localized is a powerful tool to
      address these issues, allowing to determine the exact origin of the markers and
      more refined criteria for studying karyotype-phenotype correlations. This
      facilitates genetic counseling and the decision making for the parents. Here we
      describe our experience of integrated approach (molecular and classical
      cytogenetics) in two de novo cases of marker chromosomes (iso 18p and inv dup
      15), detected at amniocentesis.

PMID- 8999385
TI  - [Ultrasonographic diagnosis of cystic hygroma at the 15th week. A case report].
AB  - The authors present a case of cystic hygroma arrived to their observation at the
      15th week. In succession to the precocious ultrasonographic screening of the
      malformation, have performed that the chromosome map have revealed that the cause
      is the trisomy 21.

PMID- 8999386
TI  - [Postpartum psychoses. A case report].
AB  - The puerperal period is a critical one in the life of a woman, due to the
      numerous changes which occur at biological and psychological levels and also at
      the level of relationships. Various disturbances of a psychiatric nature may
      emerge during this period which represents a "risky" phase from a psycho
      pathological point of view. Among some of these disturbances, so-called
      "puerperal psychoses", there is an uncertain nosographic connection. According to
      some authors, these psychoses could be distinct nosographic events, while others
      prefer to include them in psychotic disturbances which have already been
      classified. From this point of view the puerperal period would be a stressful
      event. Risk factors would be a first birth, previous psychotic puerperal
      episodes, inherited serious psychiatric disturbances and caesarean section. The
      therapy used in the case of such disturbances must take into account many aspects
      and implications which don't exclusively concern the new mother but which also
      look significantly at the newborn baby, and the patient's family circumstances.
      All this implies the necessity for a close collaboration between specialists in
      different medical areas (psychiatry and obstetrics). Particular attention should
      be given to the type of disturbed relationship which can occur between the mother
      and the new born child. The analysis of our case has stimulated many reflections
      from a clinical, therapeutic and prognostic point of view, and as a result we
      tent to agree with published material on the subject.

PMID- 8999387
TI  - [Outpatient diagnostic hysteroscopy: 14,000 cases].
AB  - Hysteroscopy is a technique which plays a fundamental diagnostic role in
      gynecological practice. The possibility of obtaining a direct intracavitary view
      and performing specific biopsies give it a greater level of diagnostic accuracy
      than intrauterine curettage. The authors' personal experience of 13,923 case
      enables the correct method of performing this procedure to be codified in order
      to avoid the inherent risks and complications. The main indication is abnormal
      uterine bleeding which is the most frequently observed pathology in gynecological
      practice. In cases of metrorrhagia in women of child-bearing age benign organic
      pathology accounts for 45% of patients and malignant pathology 0.3%. Post
      menopausal patients reveal an increase in the incidence of organic pathology in
      general and neoplastic pathologies in particular (8.1%). Complications linked to
      this type of technique are extremely rare and in overall terms affect 1% of
      cases. The analysis of results shows that hysteroscopy today represents an
      extremely reliable and repeatable outpatient procedure. However, in spite of
      these advantages, including savings in health costs, it is not widely used at a
      capillary level given that if performed by persons who are not expert it may
      become traumatic and unreliable. The correct execution of hysteroscopy in fact
      calls for dexterity acquired over time which is not conditioned by the learning
      of previous techniques and requires an adequate period of training.

PMID- 8999388
TI  - [The sexual dimorphism of the accessory olfactory system].

PMID- 8999389
TI  - [The proteinase activity and content of trypsin inhibitors in the mammae of
      female rabbits in physiological states].
AB  - We studied the activity of lysosomal cathepsins B and D, neutral trypsin-like
      proteinase, and the content of trypsin inhibitors in the mammary glands of
      virgin, pregnant, and lactating rabbit females, as well as during the involution
      caused by lactostasis. The maximal activity of cathepsin D was found to occur in
      mammary glands under the condition of lactostasis. The activity of cathepsin B
      was practically identical in the mammary glands of virgin and pregnant animals
      and diminished during lactation. The activity of trypsin-like proteinase is low
      in the mammary glands of virgin animals, increases drastically during pregnancy,
      and diminishes during lactation. The content of trypsin inhibitors is maintained
      at a similar level in the mammary glands of virgin and pregnant animals and
      increases significantly during lactation. The caseinolytic activity of neutral
      proteinases has not been detected in the mammary glands of virgin rabbit females.
      At the lactation and involution stages, it is considerably lower than the
      activity of acidic proteinases and is possibly controlled by endogenous
      inhibitors.

PMID- 8999390
TI  - [Overcoming the "2-cell block" in mouse embryos in aggregation chimeras].
AB  - The embryos of the inbred mouse strain BALB/c are predisposed to so-called "two
      cell block" after explantation from the maternal organism before the late two
      cell stage and cultivation in a standard synthetic medium. Hybrid embryos (CBA x
      C57B1) F2 are competent to complete preimplantation development in vitro. The
      BALB/c embryo predisposed to block ("blocking") at the early two-cell stage was
      aggregated using phytohemagglutinin with four to five two- and eight-cell BALB/c
      embryos capable of reaching the blastocyst stage in vitro ("non-blocking"). This
      aggregate successfully developed until the blastocyst stage for 72 h. The
      aggregation of the early two-cell BALB/c embryos with each other did not prevent
      the block. After the aggregation of the blocking and non-blocking embryos at the
      two-cell stage, a common integrated blastocyst developed. In aggregates with
      eight-cell embryos, the blocking embryo formed a separate blastocyst, although it
      preserved contacts with non-blocking embryos during the entire period of
      cultivation. Ultrastructural analysis has shown that two-cell embryos aggregated
      using phytohemagglutinin form adhesive contacts up to several microns long.
      Possible mechanisms of cooperation between the competent and deficient partners
      in aggregates with two-cell embryos are discussed.

PMID- 8999392
TI  - [The effect of a chloride channel inhibitor and of media with a decreased
      concentration of chlorine ions on spontaneous oocyte maturation in the common
      frog and the clawed toad].
AB  - Chloride-deficient media (irrespective of anions substituted for chloride)
      increased the rate of spontaneous maturation of follicle-enclosed (FEOs) and
      denuded oocytes in Rana temporaria and Xenopus laevis. The chloride channel
      blocker SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid) (10
      microM) significantly decreased the rate of the spontaneous maturation of the
      FEOs and oocytes. The addition of 10 mM (instead of 2.7 mM) calcium ions to the
      gluconate solution significantly increased the rate of the spontaneous maturation
      of FEOs of R. temporaria if it was low in the gluconate solution, and decreased
      it if it was close to 100%.

PMID- 8999391
TI  - ["2-cell block" and the viability of BALB/c embryos when explanted at the second
      cleavage cell cycle].
AB  - The embryos of BALB/c mice were explanted from hormonally stimulated females in a
      standard culture during the second cleavage division corresponding to the stage
      of the embryonic genome activation. Observations over the cultivated embryos have
      shown that explantation of the embryos both at the two-cell stage and during the
      first half of the second cleavage division brings most embryos (more than 80%) to
      the state of "two-cell block." Thereafter, the number of blocked embryos
      progressively decreases to less than 20% after explantation in the end of the
      cleavage division, which corresponds to the proportion of the embryos in the
      reproductive tract which were delayed at the 2-cell stage by the beginning of the
      third cleavage division. After explantation at the time close to the middle of
      the cleavage division, the survival of the blocked embryos is reduced and in the
      end of the two-cell stage again increases. The BALB/c embryos should stay in the
      maternal reproductive tract during the entire second cleavage division before
      explantation in order to provide for viability and developmental potencies in
      vitro close to those in vivo. The results obtained are discussed with reference
      to the controlling mechanisms of early embryogenesis and cell cycle.

PMID- 8999393
TI  - [The Moscow Seminar on Cell Biology].

PMID- 8999394
TI  - [Sulo Toivonen--a pioneer of experimental embryology].

PMID- 8999395
TI  - [Growth hormone-releasing peptides (GHRP) and their analogues].
AB  - The synthetic growth hormone-releasing peptides (GHRPs) and their nonpeptide
      analogues release growth hormone (GH). They are not only effective parenterally,
      but also intranasally and if given in the appropriate doses, they are active
      orally as well. The exact mechanism of action has not been fully established.
      There is probably a dual site of action. According to experiments on in vitro
      pituitary membranes, they directly stimulate GH secreting cells, but they are
      also active in the hypothalamus. This latter site of effect seems to be the more
      important in vivo. The presence of the endogenous growth hormone-releasing
      hormone (GHRH) is needed for their full action in humans. Their hypothalamic
      action involves either direct stimulation of GHRH neurons, or/and they act as
      functional somatostatin antagonists or possibly they act via an unknown
      hypothalamic factor. Intravenous administration causes marked GH release in
      humans and GHRPs synergise with GHRH in causing high GH output. They release GH
      in short stature children and in growth hormone deficient adults and in other
      situations of GH deficiency, such as obesity, catabolic diseases and old age. The
      role of GHRPs in the diagnosis and treatment of GH deficient states requires
      further wide-spread investigations.

PMID- 8999396
TI  - [Determination of cellular DNA content in the diagnosis and prognosis of
      mesenchymal tumors].
AB  - The authors present examples on how to use cellular DNA distribution in support
      of diagnosis, and also to predict biological behavior of mesenchymal tumours. In
      cases of smooth muscle tumours of the prostate and the uterus, on the basis of
      histological pattern, it was not possible to distinguish between bizarre cell
      (pleomorph) leiomyoma and leiomyosarcoma. The prostate tumour showed an euploid
      polyploid cellular DNA distribution pattern, supporting the diagnosis of benign
      pleomorph leiomyoma. On the other hand, the uterus tumour showed an aneuploid DNA
      content with a high S-phase fraction that is characteristic of malignant lesions.
      Cellular DNA content analysis has helped to estimate the biological behavior of a
      gastrointestinal stromal tumour originating from the stomach and a
      retroperitoneal dedifferentiated type of a well differentiated liposarcoma.
      Small, diploid tumours (< 5 cm in diameter) with a low S-phase fraction behave
      like benign tumour or malignant tumour with a low malignant potential. The
      gastrointestinal stromal tumour was diploid with 8% S-phase ratio, therefore we
      could predict favorable outcome. It means that control examination is required
      less frequently. Prognostically, the dedifferentiated type of well-differentiated
      liposarcoma differs from the common well differentiated liposarcomas; the well
      differentiated part of this tumour consisted of only one diploid subpopulation
      with a low S-phase ratio, while the poorly differentiated areas contained a
      diploid and an aneuploid cell population with a significantly higher S-phase
      fraction than that of diploid one. Aneuploidy and rapid proliferation rate refer
      to increasing genetic instability, with a clonal selection for development of a
      more aggressive cell population, thus control examination is required more
      frequently.

PMID- 8999397
TI  - [Euphenic prevention of obesity at the Optimal Family Planning Service in
      Hungary].
AB  - The body weight and height are measured and body mass index (BMI) is calculated
      in the female and male participants of the Hungarian Optimal Family Planning
      Service (which is a periconceptional care). Of 1133 female participants, 28
      (2.5%) and 91 (8.0%) were obese [> 30 kg/(m)2 BMI] or had overweight [25-29.9
      kg/(m)2 BMI]. Of 1125 male participants, 63 (5.6%) and 255 (22.7%) were obese or
      overweighted. These prospective parents were informed about the recurrence risk
      of obesity, triggering and suppressive protective factors for genetic
      predisposition and they were educated how they could reduce the recurrence of
      obesity in their planned children.

PMID- 8999398
TI  - [Use of sodium diclofenac in acute renal colic].
AB  - 31 patients with symptoms of acute renal colic were treated with diclofenac
      natrium. According to preliminary results this drug is more effective for
      relieving pain of acute renal colic than the traditional combination of
      spasmolytics and analgetics. This might be due to the blocking effect of
      diclofenac natrium on the renal PG synthesis and release, thus decreasing the
      diuresis. Side effects were minimal, as nausea, vomiting etc. Authors highly
      recommend this drug as the first choice of treatment in acute renal colic.

PMID- 8999399
TI  - [Interferon therapy in cryoglobulinemic membranoproliferative glomerulonephritis
      associated with hepatitis C virus infection].
AB  - The authors report the case of a 38 year old man with horseshoe kidney who
      developed a severe nephroso-nephritis syndrome, caused by cryoglobulinemic
      membranoproliferative glomerulo-nephritis. A combination of steroid and
      cyclophosphamide treatment resulted in partial improvement, but was discontinued
      after 12 weeks due to adverse reactions, with a consequent early relapse. The 4
      week course of cyclosporine monotherapy proved ineffective and signs of
      cryoglobulinemia appeared. The elevation of transaminase, manifested during the
      immunosuppressive therapy demonstrated the presence of underlying chronic C
      hepatitis. In the light of the liver biopsy result, interferon treatment was
      commenced at a dose of 3 million unit thrice weekly. After 4 months of interferon
      treatment the persistent nephrotic range proteinuria decreased to below 0.5
      g/day. Four months later clinical signs of cryoglobulinemia disappeared, and
      after the 10th month of interferon treatment no cryoglobulin could be detected in
      the patient's sera. After one year, the interferon treatment was discontinued
      following a negative PCR result for HCV. However, one month later the proteinuria
      increased and the quantitative hepatitis C virus nucleic acid test in sera became
      positive again. Our case demonstrates that interferon therapy may be effective in
      the treatment of cryoglobulinemic glomerulonephritis responding poorly to the
      immunosuppressive therapy, though larger doses or longer periods of treatment may
      be required to prevent relapses.

PMID- 8999400
TI  - [The correct name of the late professor of the Institute of Physiopathology at
      the Szeged Medical University is Istvan Karady].

PMID- 8999401
TI  - [The history of radiation therapy in Hungary].

PMID- 8999402
TI  - [Vaccination against Haemophilus influenzae B].

PMID- 8999403
TI  - [Symptoms and pathological anatomy of the degenerative cervical spine].
AB  - Clinical symptoms and patho-anatomic changes in cervical myelopathy due to
      spondylotic changes are described. The leading symptoms are numbness and
      clumsiness of upper and lower extremity, mostly combined with gait disturbances.
      Muscle wasting primarily on the upper extremity leads to the myelopathic hand.
      Cervical myelopathy can be classified into five main groups: 1. Spastic
      tetraparesis with numbness and hyperreflexivity of upper and lower extremity. The
      majority of patients present with the myelopathic hand. 2. Spastic paraparesis
      with lesion below C6. 3. Spastic tetraparesis, mild or moderate, with deltoid
      muscle paresis. 4. Amyotrophic myelopathic hand with mild long tract signs. 5.
      Central cord syndrome due to cervical spondylosis combined with trauma. From the
      therapeutic aspect, conservative treatment is often unsuccessful. It is important
      to relieve pressure on the spinal cord, and decompressive procedures, especially
      posterior laminoplasty techniques, are required. Earlier surgery provides better
      results.

PMID- 8999404
TI  - [Clinical and technical assessment of the cervical spine].
AB  - In analysis of the cervical and cervicobrachial syndrome with or without signs of
      compression of the nerve root or spinal cord, functional assessment of the
      cervical spine is of great importance. Comparisons between actively performed and
      passively induced motion can be verified by using standardized computer-assisted
      assessment allowing precise documentation of the range of motion and coupled
      motion. The age-related normal values should be considered. The neurological
      assessment includes not only the cranial nerves and upper extremities but also
      lower extremities to avoid overlooking the signs of cervical myelopathy. In
      patients with compression of nerve roots or the spinal cord neurophysiology might
      be helpful in identifying or verifying compression. In patients with suspected
      myelopathy sensory evoked potentials will allow assessment of the function of the
      ascending spinal pathways and motor evoked potentials, assessment of the function
      of the descending cortical spinal pathways.

PMID- 8999405
TI  - [Degenerative changes of the cervical spine. Imaging].
AB  - Standard radiography of the cervical spine is still the first imaging procedure
      applied in degenerative disease of the cervical spine. Spondylosis deformans,
      osteochondrosis and uncovertebral arthrosis are well depicted by such images.
      Whether or not additional imaging is needed depends on the clinical symptoms.
      Special projections (anteroposterior oblique radiographs, lateral radiographs in
      flexion and extension) may be the next step. For many abnormalities, mainly of
      the intervertebral discs and the myelon, MR imaging has become the standard
      procedure, largely because of its multiplanar capabilities and its excellent
      contrast resolution. CT can be used instead of MR imaging if the latter method is
      not available, and its strength lies in the depiction of bone abnormalities.
      Scintigraphy is suitable for early detection of abnormalities with unclear
      clinical symptoms and may then indicate the correct level of the cervical spine
      for MR imaging or CT. Myelograms and myelo-CT can no longer be considered routine
      imaging methods. A number of imaging abnormalities are not strictly related to
      clinical findings and should therefore always be discussed in the clinical
      context.

PMID- 8999406
TI  - [Functional treatment of diseases and injuries of the cervical spine].
AB  - The clinical findings and pain symptoms determine the functional treatment of the
      cervical spine disorders. Acute pain syndromes are to be approached by passive
      procedures, such as massage, electrotherapy, trigger point treatment. Could the
      pain reaction be reduced, the mobilizing techniques, including manipulation are
      indicated, followed by training therapy/reconditioning of shoulder girdle
      muscles. The patients are also to be instructed to perform home exercise program
      aiming the stabilization of cervical spine.

PMID- 8999407
TI  - [Injection therapy in cervical syndromes].
AB  - Injection therapy is highly significant in the treatment of cervical syndromes.
      Following the differential diagnosis and analysis of the symptoms, injection
      treatment leads to a worthwhile degree of pain relief as a result of the
      anaesthetic effect on the nerve. This paper describes the general criteria for
      such treatment and also the various injection techniques in use.

PMID- 8999408
TI  - [The dorsal approach in degeneratively changed cervical spine].
AB  - The posterior approach to the cervical spine was the only method of access to the
      spinal canal until the anterior approach was developed by Robinson and Smith, and
      Cloward. With the accumulation of experience in posterior decompression for
      cervical spondylotic myelopathy (CSM), successful laminectomy was guaranteed only
      when lordotic alignment of the cervical spine, wide and extensive laminectomy for
      adequate posterior shift of the spinal cord, and stability of the spine were
      ensured after surgery. The thick scar formation occasionally seen subsequent to
      postlaminectomy hematoma could lead to an unfavorable outcome. The insertion of
      surgical instruments, such as a Kerrison rongeur or a curette, into the spinal
      canal without being aware of how narrow the canal is, or uneven decompression of
      the spinal cord during resection of the laminae can impinge on or distort the
      spinal cord and result in deterioration of neurological function. Several authors
      have pointed out that postoperative loss of neural function is a hazard of
      surgical intervention. Owing to the poor results of conventional laminectomy for
      cervical compression myelopathy related to the problems mentioned above, Kirita
      developed extensive simultaneous decompression laminectomy to avoid distortion of
      the spinal cord by the edges of the resected laminae. Hattori devised an
      expansive Z-shaped laminoplasty in which the posterior wall of the spinal canal
      was preserved by Z-plasty of the prepared laminae. This was an attempt to prevent
      the invasion of scar tissue, i.e., the so-called laminectomy membrane, which was
      believed to be a cause of late neurological regression. He also expected that the
      laminae reconstructed by Z-plasty would provide support for the spine. The
      introduction of high-speed air-drills allowed successful development of this
      procedure. In 1977, Hirabayashi introduced an epoch-making laminoplasty, the
      expansive open-door laminoplasty. He described the advantages of this procedure
      as: possibility of decompressing multiple levels of the spinal cord
      simultaneously, better postoperative support of the neck, allowing earlier
      mobilization of the patients, prevention of postoperative kyphotic deformity of
      the cervical spine, and reduced mobility of the cervical spine postoperatively,
      which helps to prevent late neurological deterioration and progression of OPLL.
      Subsequent to the Hirabayashi laminoplasty, various modifications and
      supplementary procedures have been devised for further improvement of the safety
      and efficacy of decompression, and for improved stability of the spine. Aims,
      advantages and disadvantages of laminoplasty: The aims of the laminoplasty are to
      expand the spinal canal, to secure spinal stability and to spare the protective
      function of the spine. Preservation of mobility of the spine is also a goal of
      this procedure for multiple level involvement. Decompression can be extended
      along the nerve root by facetectomy. Preservation of the posterior spinal
      structures permits reinsertion of the nuchal muscles and the spinal ligaments
      after they have been totally or partially detached. This prevents kyphosis or
      listhesis of the cervical spine, which often develops after laminectomy,
      particularly in subjects below 50 years of age. Reconstructive procedures for
      reattaching muscles and/or ligaments to the spinous processes are added to the
      laminoplasty, improving the dynamic or ligamentous stability of the spine.

PMID- 8999409
TI  - [Post-traumatic atlanto-axial arthrosis].
AB  - Eight patients with post-traumatic chronic cervical syndrome and degenerative
      changes of the upper cervical spine, were treated with suboccipital fusion. After
      a mean follow up of 60 months (58-64), the patients were examined. Three patients
      had died during the follow-up period. A solid fusion was achieved in all cases.
      Significant reduction of pain and increased quality of life were established.

PMID- 8999411
TI  - [Surgical therapy in radicular symptoms of the degenerative cervical spine].
AB  - Radicular pain is a common feature in day-to-day clinical practice. Only a small
      percentage of patients with persistent pain and/ or neurological deficit need
      surgical decompression. Exact anatomical localization of the decompressive agent
      and the correlation of clinical symptoms and radiological findings are mandatory.
      In most cases, surgery is performed by an anterior approach; by which the
      causative agent is removed. In cases with narrowing of the neural foramen total
      resection of the uncus is indicated. Additional fusion supports the physiological
      cervical lordosis.

PMID- 8999410
TI  - [Micro-technological anterior discectomy without fusion in cervical disk
      displacement with radicular symptoms].
AB  - Only cervical disc herniation that provokes root compression unresponsive to
      conservative treatment should be selected for operation. The operative technique
      must allow adequate removal of the disc and relieve any root pressure without
      distressing the patient. Operative decompression of the root can be attained via
      laminectomy and arthrotomy or by way of an anterior approach. With this second
      procedure, the ventral discectomy can be done in conjunction with an interbody
      fusion. We report our experience with 216 patients who underwent anterior
      cervical microsurgical discectomy without fusion between 1980 and 1944. All these
      patients were suffering from compressive cervical radiculopathy caused by disc
      displacement without significant degenerative deformation of the motion segment
      and without manifest segmental instability. The follow-up ranged between 6 and
      185 months (average 71 months) in the 175 patients in whom it was possible. Only
      in 7 patients (4%) is the result unsatisfactory; 79 patients (45%) are completely
      free of symptoms 99; (56.6%) are very satisfied and 45 (25.7%) satisfied with the
      result of the procedure.

PMID- 8999412
TI  - [Surgical therapy of spondylogenic cervical myelopathy. Indications and
      techniques].
AB  - The cervical spondylotic myelopathy is the most frequent spinal dysfunction. Its
      spontaneous course is very variable, from progress to stagnation. This makes
      prognosis and decision-making difficult for conservative or operative treatment.
      The authors attempt to provide some basis for decision-making by observing the
      individual course of neural dysfunction, consideration of morphometric data and
      the use of functional scores. To advise a patient, the outcome of conservative
      and operative treatment as described in the literature has to be considered, as
      well as the possible complications. The advantages and disadvantages of surgery
      from the anterior and posterior approach are discussed. Operative planning
      according to the individual condition is suggested. Operative techniques of
      anterior decompression and fusion are contrasted to laminoplasties.

PMID- 8999413
TI  - [Bone metabolism and diseases].

PMID- 8999414
TI  - [The use of the methods of geometrical morphometry in the systematics of ixodid
      ticks (Ixodidae)].
AB  - It is shown that morphological characters, such as a form of gnathosoma, usually
      considered as qualitative one, may be properly analyzed on a quantitative basis
      by means of the geometrical morphometric methods. In particular, an extraction of
      relative warps (RW) from a shape variation using TPSRW computer program makes it
      possible to run standard statistical procedures over matrices of RW values. This
      approach is demonstrated by the analysis of gnathosoma shape differences in 4
      Ixodes species and 3 Dermacentor species, with a discriminant analysis being
      employed as a statistical routine. It is shown that differences among I.
      persulcatus and I. ricinus are statistically significant (by F-criterium) in all
      ontogenetic phases, while in the case of I. laguri and I. redikorzevi this is
      true only for the larval phase. Magnitudes of the gnathosoma shape variation
      among species (by F criterium) are similar within both Ixodes (s, str.) and
      Serdjukovia subgenera. The differences among subgenera of the genus Dermacentor
      are more significant.

PMID- 8999415
TI  - [The T and B immunity systems in eimeriosis (Eimeria tenella) in domestic
      chickens].
AB  - It has been shown that the three fold immunisation of 30 day old chicken with 10,
      50 and 100 thousand oocysts of E. tenella at intervals 15 day induces increasing
      amounts of T- and B-lymphocytes in thymus, spleen and bursa of Fabricius. The
      mode of lymphocyte dynamics at immunization is considered in terms of host
      parasite relationships, possible ways of anti-eimerian immunity formation being
      discussed.

PMID- 8999416
TI  - [Parasitic systems and the population structure of parasitic organisms].
AB  - The analysis of population systems is carried out on the basis of the
      classification of spatial and functional structure of populations developed by V.
      N. Beklemishev. Two aspects of the structure of population systems are
      established. Firstly, population systems are composed of the smaller groups
      characterised by different self-maintenance ability. Secondly, different
      functional parts are included into these systems in accordance with different
      stages (phases) of a life cycle. Peculiarities of the population systems are
      discussed from these points of view. The population system is a functional part
      of a particular community. Steady interrelationships between population systems
      in the community ("community links") are the basis on which the complexes of
      population systems in different species are formed. A prominent example of this
      is the parasitic systems, that is the population system of a parasite and all
      connected populations of its hosts. The structure of a parasitic system is
      examined. In general, it is characterised by a) peculiarities of the life cycle
      of the parasite, since its population systems are the organising component of the
      parasitic system; b) subdivision of the environment for parasites. The first
      trait is discussed from the standpoint of phase structure of populations which is
      could be clearly seen in parasites, and the second one-from the viewpoint of the
      availability of distinct microbiotopes connected with different parts of the
      population system of parasites. It is the subdivision of the parasites'
      environment and its organisation according to the scale (interspecies,
      interpopulation or intrapopulation) variability of the hosts, that make it
      possible to recognise spatial and functional parts in the framework of the
      parasitic system. The critical review of the terminology used in the population
      parasitology is presented.

PMID- 8999417
TI  - The geographic variation of suicide rates by solid and liquid substances.
AB  - Suicide rates by solids and liquids in the 48 contiguous states in 1980 were
      associated with percentage of people born in-state and longitude as was the total
      suicide rate and the suicide rate by firearms. The implications of these findings
      were discussed.

PMID- 8999419
TI  - [Assessment of myocardial viability using 201TL SPECT at rest to predict the
      reversibility of left ventricular wall motion abnormalities].
AB  - AIM: The aim of the present study was to predict preoperatively the reversibility
      of left ventricular wall motion abnormalities using TI-201 SPECT at rest.
      METHODS: 19 patients with advanced coronary artery disease and regional wall
      motion abnormalities were examined at rest with TI 201 SPECT (acquisition 15
      minutes and 3 hours post injection). Successfully revascularized, proven by a
      second coronary angiography three month after revascularisation. Wall motion was
      again evaluated by cineventriculography. RESULTS: The preoperative a- or
      dyskinetic segments were best separated by the minimal relative TI-201 uptake in
      the defect 3 hrs p.i. in (i) postinterventionally improved wall motion (TI-201
      uptake 67 +/- 14%, viable) and in (ii) without recovery (TI-201 uptake 46 +/-
      12%, p < 0.001, non viable). A threshold at a TI-201 uptake of more than 50%
      yielded a positive predictive value of 0.73 and a negative predictive value of
      0.86. If the segments with wall motion abnormalities (hypokinetic included) were
      evaluated as one group, no such threshold was obtained all segments which
      occurred a TI-201 uptake of more than 80% showed a functional recovery, wall
      motion did not improve in any segment with a TI-201 uptake of less than 40%. In
      the present study a considerable influence of the defect localisation with regard
      to the posterior wall was not observed. The values of TI-201 redistribution under
      resting condition were not useful to predict functional recovery. CONCLUSION: TI
      201 SPECT in rest predicts preoperatively the reversibility in regions with
      severe wall motion abnormalities only and indicates myocardial viability in these
      cases. Thus, the method is basically useful to determine myocardial viability. In
      hypokinetic segments, however, a wide range of TL-201 uptake values exists
      without definite evidence to functional recovery.

PMID- 8999418
TI  - [Impairment of myocardial perfusion reserve in microvascular angina (syndrome X):
      assessment by 99mTc-MIBI-SPECT].
AB  - AIM: In 22 patients with typical chest pain and normal coronary arteries
      (microvascular angina, syndrome X) 99mTc-MIBI-SPECT was examined in regard to
      assess impairment of myocardial perfusion reserve. METHOD: The study was
      performed with 99mTc-MIBI-SPECT at rest and under vasodilation with dipyridamole.
      The findings were compared with a normal database. A normal perfusion reserve was
      said to be an increase > 20% of the 99mTc-MIBI-activity. RESULTS: In 2/22 (9%) of
      the patients the perfusion reserve lay > 20% i.e. 37%. In 91% of the patients a
      diminution or even decrease of the perfusion was to be seen. From these 9/22
      (41%) of the patients showed a diminution of the 99mTc-MIBI-uptake by 6%. 1/22
      patients had a decrease of the perfusion under vasodilation with dipyridamole
      i.e. a lower activity of 99mTc-MIBI by 13% CONCLUSION: Vasodilation 99mTc-MIBI
      SPECT offers good imaging quality and enables semi-quantitative assessment of
      myocardial perfusion reserve in patients with microvascular angina.

PMID- 8999420
TI  - [Pseudodefects in myocardial SPECT after implantation of defibrillator patches:
      phantom measurement with SPECT and PET].
AB  - AIM AND METHODS: In order to estimate the effect of an epicardial or subcutan
      defibrillator patch electrode on the imaging of myocardium with SPET and PET we
      performed measurements with a body phantom and two different patch electrodes.
      RESULTS: We found that in 201TI-SPET with epicardial placing one electrode causes
      significant pseudodefects, which might lead to the impression of an infarction
      ("pseudoinfarction"), particularly in the case of reduced myocardial wall
      thickness. Measurements with 99nTc show the same pseudodefects. In case of
      subcutaneous placing the electrodes are much less likely to cause relevant
      absorption effects. With PET even epicardially placed both patch electrodes do
      not produce pseudodefects. Therefore the risk of false-positive findings is very
      small with PET. CONCLUSION: In order to avoid false positive findings in
      cardiovascular nuclear medicine caused by defibrillator patch electrodes,
      patients with patch electrodes should be referred to PET, if available.

PMID- 8999421
TI  - [Follow up control of stage IV neuroblastoma: 123I-MIBG scintigraphy, bone
      scintigraphy and catecholamine metabolites].
AB  - AIM: The diagnostic value of 123I-mIBG-scintigraphy, bone scintigraphy and
      catecholamine metabolites in the follow up of neuroblastoma stage IV will be
      evaluated. METHODS: Nineteen children suffering from neuroblastoma were analysed
      retrospectively by 123I-mIBG-scintigraphy, bone scintigraphy and measurement of
      homovanillic acid, vanillic acid, neuronspecific enclose, lactate dehydrogenase,
      and ferritine. Follow up was 7-132 (median 36) months. RESULTS AND CONCLUSION:
      The significance of the methods was dependent on the time of diagnostic use. In
      principal, 123I-mIBG-scintigraphy has the highest diagnostic impact. For initial
      staging and diagnosis of recurrence a combination of all three methods can be
      used. On the contrary, follow up during chemotherapy is best documented by 123I
      mIBG-scintigraphy, whereas bone scintigraphy is of limited and measurement of
      catecholamine metabolites of less diagnostic value.

PMID- 8999423
TI  - [Semiquantitative 99mTc-HMPAO SPECT in dementia of the Alzheimer type: influence
      of the selection of reconstruction filter and reference region].
AB  - AIM: The aim of the study was to clarify, whether the selection of the reference
      region and/or the reconstruction-filter influences the result of the
      semiquantitative analysis of a 99mTc-HMPAO-SPECT that was conducted to diagnose
      the dementia of the Alzheimer type (DAT). METHODS: A group of 19 DAT-patients
      according to the criteria of NINCDS-ADRDA and DSM-III-R was examined together
      with a comparison group (n = 14) with normal cerebral perfusion. Three reference
      regions (cerebellum, whole slice, occipital cortex) and four reconstruction
      filters (Hanning fc = 0.7 and 1.0 Nyquist; Butterworth (n = 8); fc = 0.5 and 0.9
      Nyquist) were applied to twelve standardized regions of interest (per patient)
      respectively. The data was evaluated through a ROC-analysis. RESULTS: It has been
      showed, that the bilateral parieto-temporal perfusion reduction as a
      characteristic of DAT depends on the filters and reference-regions used. The most
      secure separation of both groups of patients was obtained through a Butterworth
      filter (n = 8; fc = 0.5) in combination with the cerebellum as reference-region.
      CONCLUSION: The selection of the reference-region and the reconstruction-filter
      has an important influence on the results of a semiquantitative analysis.
      Therefore standardisation in dependency on the actual questioning is necessary.

PMID- 8999422
TI  - [Lymphoscintigraphy for non-invasive long term follow-up of functional outcome in
      patients with autologous lymph vessel transplantation].
AB  - AIM: Autologous lymph vessel transplantation significantly improves the
      lymphdrainage in patients with primary and secondary lymphedema. The aim of the
      present study was to answer the question, whether scintigraphic long-term follow
      up and semiquantitative evaluation of lymphatic flow could prove the persisting
      success of this sophisticated microsurgical technique. METHODS: In this study
      visual and semiquantitative lymphoscintigraphy was used to prove the function of
      lymphatic vessel grafts in 20 patients (17 females, 3 males) comparing a
      preoperative baseline study with postoperative follow up investigations for a
      period of 7 years. The reason for microsurgical lymph vessel transplantation was
      in 4 patients a primary and in 16 patients a secondary lymphedema. In 12 cases
      the transplantation site was at the upper extremity, in 8 cases at the lower
      limb. RESULTS: In 17/20 patients lymphatic function significantly improved after
      autologous lymph vessel transplantation compared to the preoperative findings, as
      verified by visual improvement of lymph drainage and decrease of a numeric
      transportindex. In 5 cases the vessel graft could be directly visualized. In
      these patients with scintigraphic visualization of the vessel graft the
      transportindex decreases to a significantly greater extent compared to the
      preoperative baseline study. Only 3 patients did not benefit from microsurgical
      treatment CONCLUSION: Lymphoscintigraphy combined with semiquantitative
      estimation of lymphatic transport kinetics has shown to be an easy, reliable and
      readily available technique to assess lymphatic function before and after
      autologous lymph vessel transplantation. Thus, the method is not only helpful in
      planning microsurgical treatment but also in monitoring the postoperative
      improvement of lymph drainage. Patients with scintigraphic visualization of the
      vessel graft showed a significant better postoperative outcome than those
      without. The scintigraphic visualization of the vessel graft therefore seems to
      indicate a favourable prognosis regarding to lymph drainage.

PMID- 8999424
TI  - [Influence of physiological and pharmacological amounts of iodine on the 131I
      uptake of the thyroid gland--a model calculation].
AB  - AIM: The aim of this paper was to use a iodine metabolism model in order to
      analyze theoretically the different aspects of the iodine metabolism. METHOD: To
      perform this a three compartment model was developed. RESULTS: With this model we
      examined the influence of physiological and pharmacological iodine amounts on the
      iodine-131 uptake in the thyroid gland and additionally the excretion of Iodine
      131 after radiotherapy. It can be said, that an in-patient admission for a
      duration of at least three days to perform a radiotherapy is sensible (wise) and
      a iodine-poor diet prior to the radiotherapy is of advantage. Regarding the
      iodine blockade of the thyroid gland after a reactor accident the effects
      (outcome) of the German recommendations were compared with the WHO-guidelines.
      CONCLUSION: The model of iodine metabolism is suited for analyses even if because
      of ethic or other limitations measurements at human beings are not possible.

PMID- 8999425
TI  - [Thyroid gland scintigraphy for in vivo presentation of the signal transduction
      cascade and beyond].

PMID- 8999426
TI  - [Myopericarditis and auricular fibrillation disclosing septicemic leptospirosis].

PMID- 8999427
TI  - Michael reactions of ascorbic acid, 4th communication: nitrostyrene as a Michael
      acceptor toward vitamin C.
AB  - The nitrostyrene derivatives 1a-m, prepared by the reaction of nitromethane with
      the appropriate substituted benzaldehyde, were reacted with ascorbic acid in a
      Michael type reaction to the new compounds 2a-h. The structural assignment of the
      resulting mixture of diastereomers could be performed by means of two dimensional
      homo- and heterocorrelated NMR spectroscopy and comparison to known Michael
      adducts of ascorbic acid. Catalytic hydrogenolysis of 2a yielded the rearranged
      compound 7, formed by intramolecular aminolysis in analogy to the rearrangement
      of the Michael adduct of ascorbic acid and methylvinylketone 3 given in the
      literature. On testing, the C-nucleoside 7 did not reveal virostatic or
      cytostatic effects.

PMID- 8999428
TI  - The biological activity of two symmetric amine derivatives of the cis-syn-cis
      triquinane system.
AB  - N-benzyl-3,11-azatricyclo[6.3.0.0]undecane and N-octyl-3,11
      azatricyclo[6.3.0.0]undecane, two triquinane compounds containing an endocyclic
      nitrogen atom and differing side-chains, were synthesized by thermal 2 + 2
      cycloreversion from the symmetric cage compound pentacyclo[5.4.0.0.0.0]undecane
      8,11-dione. The conformation of the cyclic system showed close similarity with
      the conformation of the hydrate of 4-methyltricyclo[6.3.0.0]undeca-3,11-dione.
      Both N-benzyl-3,11-azatricyclo[6.3.0.0]undecane and N-octyl-3,11
      azatricyclo[6.3.0.0]undecane showed similar suppressant activity on the Ca2+
      action potential of guinea-pig papillary muscle--the benzyl (aromatic) derivative
      fully suppressed the action potential (AP) whilst the aliphatic (octyl)
      derivative suppressed the AP to about 50% at the same dosages. Similarly, both
      these compounds (irreversibly) suppressed the chronotropy of spontaneously
      contracting guinea-pig atria by approximately 30% at concentrations of 1 x 10(-5)
      M or more.

PMID- 8999429
TI  - Synthesis and tumor inhibiting activity of lanthanum (III) complexes with some 1
      aminocycloalkancarboxylic acids.
AB  - Complexes of La(III) with 1-aminocyclopentane-, -hexane, -heptane and -4
      ethylcyclohexanecarboxylic acids were obtained. The compounds were characterized
      by elemental analyses, IR spectroscopy and conductivity measurements. The
      following general formula was derived: LaL3Cl3 x 5 H2O, where L is the
      corresponding 1-aminocycloalkanecarboxylic acid. The pharmacological studies
      showed that all complexes manifested higher cytostatic and cytotoxic effects in
      comparison with lanthanum chloride. Much higher cytotoxic (anti-P388/D1) and
      cytostatic (anti-L-1210 and anti-melanoma-B16) activity was found for the
      lanthanum complex with 1-aminocyclopentanecarboxylic acid.

PMID- 8999430
TI  - 1-Methyl-1H-2-imidazo[4,5-b]pyridinecarboxylic acid and some of its derivatives
      with suspected antituberculotic activity.
AB  - 2-Hydroxymethyl-1-methyl-1H-imidazo[4,5-b]pyridine was obtained and its oxidation
      was carried out. 1-Methyl-1H-2-imidazo[4,5-b]pyridinecarboxylic acid, its methyl
      ester, amide, nitrile, thioamide, amidoxime, hydrazide and hydrazidehydrazones
      were synthesized. Willgerodt-Kindler reaction of 1,2-dimethyl-1H-imidazo[4,5
      b]pyridine was investigated. Some of the obtained compounds were tested for
      antituberculotic activity.

PMID- 8999432
TI  - QSAR analysis of a set of benzimidazole derivatives based on their
      tuberculostatic activities.
AB  - A set of benzimidazole derivatives previously tested for their tuberculostatic
      activities was analyzed using the quantitative structure activity relationship
      (QSAR) method. The activity contributions for structural and substituent effects
      were determined from the correlation equations which were derived using stepwise
      regression technique. The resulting QSAR showed that the activity contributions
      of benzimidazoles depend on the size of the substituents at R2, the field effect
      of the substituents at R1 and structural parameter IY which indicates the
      presence of oxygen between the benzimidazole and benzyl or phenyl groups.

PMID- 8999431
TI  - Synthesis and in vitro investigations of nalidixic acid amides of amino acid
      esters as prodrugs.
AB  - For a new DDS of nalidixic acid (1) to overcome its therapeutic drawbacks, amides
      of glycine ethyl ester and the methyl esters of alanine, phenylalanine, leucine,
      isoleucine and valine, 2(a-f), were synthesized as prodrugs. The stability of the
      prepared prodrugs in pH 1.2, 7.4 and 80% human plasma was investigated and showed
      higher stability in the buffers than in the plasma. It was noticed that the
      reversion of the parent drug from the synthesized prodrugs occurred through two
      steps, the first was hydrolysis of the ester moiety with formation of nalidixic
      acid amides of the amino acids as intermediates. The second step was the
      hydrolysis of these intermediates to 1 and the corresponding amino acid. The
      prodrugs showed an increase in the lipophilicity compared with 1 as indicated
      from the log P values. The plasma protein binding potency was studied in vitro
      using BSA and revealed a decrease in the percentage bound in case of glycine and
      alanine derivatives (of low lipophilicity) and increase in the percentage bound
      of phenylalanine, leucine and isoleucine derivatives (of high lipophilicity).
      Lower binding potency and higher lipophilicity was observed in the case of valine
      derivative, that was suggested to be owed to some steric hindrance with the
      binding sites.

PMID- 8999433
TI  - Design and in vivo testing of 17 beta-estradiol-HP beta CD sublingual tablets.
AB  - 17 beta-Estradiol is almost insoluble in water. The effect of various
      cyclodextrins and two different polymers, polyvinylpyrrolidone (PVP) and
      carboxymethylcellulose (CMC), on the aqueous solubility of 17 beta-estradiol was
      investigated. 17 beta-Estradiol was dissolved in aqueous 50% w/v 2-hydroxypropyl
      beta- cyclodextrin (HP beta CD) solution containing 0.25% (w/v) CMC and the dry
      17 beta-estradiol-HP beta CD complex formed by lyophilisation of the solution.
      Sublingual tablets from the dry complex were produced by direct compression. The
      dissolution of 17 beta-estradiol from tablets containing the drug in a
      lyophilised HP beta CD complex was determined. For reference the dissolution of
      17 beta-estradiol was determined from tablets containing physical mixture of 17
      beta-estradiol and HP beta CD or tablets containing 17 beta-estradiol without HP
      beta CD. Sublingual tablets containing 17 beta-estradiol-HP beta CD in the
      lyophilised complex demonstrated the fastest dissolution profile and those
      tablets were selected for further studies in humans. Six postmenopausal women
      received a sublingual tablet containing 17 beta-estradiol-HP beta CD complex
      equivalent to 100 micrograms 17 beta-estradiol. Blood samples were collected over
      a 12 h period and the 17 beta-estradiol plasma concentration was determined. 17
      beta-Estradiol was rapidly absorbed from the sublingual tablets, resulting in a
      peak 17 beta-estradiol plasma concentration of 568 +/- 97 pmol/l 15 min after
      administration of the tablets, followed by a biphasic elimination.

PMID- 8999434
TI  - Improvement of some pharmaceutical properties of drugs by cyclodextrin
      complexation. 5. Theophylline.
AB  - The interaction of theophylline (TPH) with beta-cyclodextrin (beta-CD) was
      investigated by spectrophotometry, vapour pressure osmometry and DSC. The results
      revealed a molecular interaction between TPH and beta-CD. The continuous
      variation method was used to elucidate the stoichiometry of such an interaction
      by spectrophotometric as well as vapour pressure measurements. Both types of data
      revealed the formation of two-to-one TPH/beta-CD complex. The stability constant
      of the complex was determined at different temperatures by the vapour pressure
      osmometric method. The enthalpy and entropy of the interaction were evaluated and
      the results indicate the liberation of little heat during complexation and the
      disorder of the guest molecule upon complexation. The effect of beta-CD on the
      solubility of TPH indicates that beta-CD exhibits a definite solubilizing effect
      towards the drug with a typical Bs isotherm. The stability constant of the
      complex and the amount of drug solubilized in the form of complex reveal that
      complex-formation is the only factor governing the solubilizing effect of beta-CD
      towards the drug. The dissolution rates of TPH, TPH/beta-CD physical mixture as
      well as the prepared complex were determined according to U.S.P. method and at pH
      1.2. In both cases, the dissolution profile of the complex reveals enhanced
      dissolution properties compared to the drug. The effect of beta-CD on the
      partition properties of TPH reveals decrease in presence of beta-CD. The effect
      of beta-CD on the bioavailability of TPH was investigated in human subjects. A
      clear difference in the biological performance between the drug and the complex
      was revealed. The pharmacokinetic parameters including Cmax, tmax, Cmin, t1/2,
      Ke, MRT and AUC revealed that inclusion complexation of theophylline in B
      cyclodextrin results in not only an improvement in the bioavailability of the
      drug, but also to acquired sustained release properties for the drug.

PMID- 8999435
TI  - Lack of pharmacokinetic interaction between dextromethorphan, coumarin and
      mephenytoin in man after simultaneous administration.
AB  - The possible interference of simultaneously given dextromethorphan (10 mg
      dextromethorphan-HBr-H2O), coumarin (10 mg), and mephenytoin (100 mg (R/S)
      mephenytoin) on oxidative routes of drug metabolism performed by different
      cytochrome P450 enzymes and the possibility to detect all of the three substances
      and their metabolites in urine were investigated in 12 healthy subjects. The
      concentrations of parent drugs and main metabolites were measured in urine using
      modified HPLC-methods. All subjects were extensive metabolizers of mephenytoin
      and dextromethorphan as calculated using hydroxylation index (HI) for mephenytoin
      and as seen in the quantification of urinary dextromethorphan/dextrophan. A
      combined determination of coumarin and dextromethorphan with their metabolites or
      of coumarin and mephenytoin with their metabolites in urine is possible. The
      combined HPLC separation of all parent compounds and metabolites, however, is not
      useful because of the necessity to treat the urine samples in very different
      ways. An overlapping of retention times of the substances in HPLC does not occur.
      With it a simultaneous administration of all three drugs is possible. A following
      collection of urine over a period of 8-12 h serves for characterizing activities
      of different cytochrome P450 enzymes of patients. So particularly the influence
      of a long term drug therapy on the hydroxylation activities of these cytochromes
      is easily definable without the disturbing influence of intraindividual variation
      of drug oxidation with time.

PMID- 8999437
TI  - Effect of organic ammonium salts on metabolic processes in Pseudomonas
      aeruginosa.
AB  - The effect of a homologous series of 2-(dodecanoylamino)-ethylalkyl
      dimethylammonium bromides on the cell metabolism of a Pseudomonas aeruginosa
      strain isolated from a nosocomial infection was studied. The inhibition of the
      incorporation of radioactive precursors into macromolecules (DNA, RNA, proteins)
      was dependent on the length of the alkyl chain of the tested substances. Similar
      results were noted also by following the inhibition of the endogenous respiration
      of P. aeruginosa. The most effective substance at suppression of [14C] precursors
      incorporation was with hexyl, and in the case of respiration, the substance with
      octyl in the molecule. The total inhibition of the respiration in the presence of
      exogenous carbon substrates, i.e. glucose and glycerol, was found with the
      substance containing the octyl group (conc. 100 micrograms/ml). We assumed that
      the studied substances interfere with cell energy-carbon metabolism of P.
      aeruginosa.

PMID- 8999436
TI  - Lipid peroxidation during acute stress.
AB  - Lipid peroxidation (LPO) is one of the main events induced by oxidative stress.
      The aim of our study was to investigate the influence of 30 min cold
      immobilization (model of acute stress used in this experiment) on LPO in the
      brain, heart, liver and stomach homogenates of the rats. LPO was determined by
      measuring of the contents of thiobarbituric acid reactive substances (TBARS),
      conjugated dienes (CD) and sulfhydryl groups (SH). Experimental stress induced
      enhancement of TBARS formation in the liver and increased level of the CD in the
      heart, stomach and liver, while in the brain both parameters were found to be
      decreased. The levels of TBARS were not changed in the heart and in the stomach,
      too. The concentrations of SH-groups were decreased in the heart, brain and
      stomach, while in the liver the parameter was found to be not changed. The
      results of this study showed the increase of LPO in the heart, stomach and liver
      under stress conditions. It could be supposed that LPO may be involved in
      mechanisms of stress injury in different tissues.

PMID- 8999438
TI  - In vitro activity of synthetic bromo analogs of pyrrolmycins against clinical
      Staphylococcus aureus strains.

PMID- 8999439
TI  - Synthesis of aminothienopyrimidine and thienotriazolopyrimidine derivatives as
      potential anticonvulsant agents.
AB  - New aminothienopyrimidines and derivatives of the new thienotriazolopyrimidine
      ring system were synthesized to investigate their anticonvulsant activity. The
      tricyclic compounds 6a, c, e, f, m, o and p and two bicyclic derivatives 4f and
      4o were tested. The pharmacological screening results are reported and discussed.

PMID- 8999440
TI  - [Comparison of serum concentrations of caffeine, 4-methylaminoantipyrine,
      sulfamethazine and debrisoquin following oral administration of these substances
      as a cocktail in type II diabetics before and after insulin therapy].
AB  - A cocktail of 4 substances (caffeine/CYP1A/CYP1A2, metamizol/CYP2B,
      debrisoquin/CYP2D6 and sulfamethazine/N-acetyltransferase) was administered to 15
      maturity-onset diabetics before and 6 months after insulin therapy (IT) to
      examine changes in hepatic biotransformation capacity in humans under
      pathological conditions. Blood and urine samples were taken 6 h after oral
      administration of the drugs. There were no differences in acetylation- and
      hydroxylationsphenotyping before or during IT. However, a significant increase in
      concentration of free sulfamethazine during IT can be interpreted as induction of
      N-acetyltransferase by poor metabolic control. Comparison of caffeine
      concentration showed no significant differences. Obviously in humans CYP1A2 is
      not influenced by type-II-diabetes mellitus. Concentration of 4-methyl
      antityprine (4-MAA), a metabolite of metamizol, was significantly increased
      during IT. This results shows a possible induction of CYP2B by poor metabolic
      control.

PMID- 8999441
TI  - [The area where neurological science and psychiatry meet].

PMID- 8999442
TI  - [Ultrasound guided puncture of the portal vein in transjugular intrahepatic
      portasystemic stent shunt (TIPSS)].
AB  - Successful completion of a transjugular intrahepatic portosystemic stentshunt
      (TIPSS) relies on knowledge of the individual hepatic vascular anatomy. The
      patients referred for TIPSS have an increased risk of contrast-medium-induced
      renal failure, and therefore the potential for a complete angiographic work-up
      during the procedure is limited. The same patient population also carries an
      increased risk of bleeding, which necessitates a rather accurate guiding
      technique for portal punctures. We have established transcutaneous sonographic
      guidance as a standard technique for transjugular portal puncture, reducing
      complication rates and intervention time. Competing imaging modalities for
      guidance are discussed.

PMID- 8999443
TI  - [CT-guided puncture].
AB  - Sonographic and CT-guided punctures allow the evaluation of suspected lesions in
      the head, thorax, abdomen, retroperitoneum and skeletal system. The size of the
      lesion to be evaluated determines the size and the diameter of the puncture
      needle. The quantity of the material obtained will be defined by the diameter of
      the needle, i.e. fine-needle biopsy is more adequate for cytological than for
      histological evaluation. Strict adherence to the indications and
      contraindications for puncture and painstaking performance of the procedure go a
      long why towards minimizing the complications. The advantage of CT-guided
      puncture, in contrast to an ultrasound-guided procedure, is visualization during
      the puncture procedure free from overshadowing. This permits punctures of lesions
      located deep in the thorax or the abdomen which are overshadowed by the lungs, by
      air in the small or large bowel or by bone structures. Moreover, this technique
      yields much more information about the tissues and organs surrounding the
      suspected lesion. This information is much more investigator-related with
      ultrasound-guided puncture. Therefore, the CT-guided puncture has become
      mandatory in the evaluation of suspected lesions. Moreover, using the same
      technique, percutaneous drainage of fluids in the interpleural space, abscesses
      in organs, hematomas, lymphoceles and urinomas; ablation of metastases; and
      sympathicolysis can be carried out. CT-guided puncture thus changes from a
      minimally invasive diagnostic procedure to a minimally invasive therapy.

PMID- 8999445
TI  - [CT-assisted definition of puncture site and penetration angle for percutaneous
      lumbar diskectomy].
AB  - In 20 consecutive patients submitted to CT evaluation of a suspected disk
      protrusion at level L4-5, CT measurements to define entry point and penetration
      angle for percutaneous diskectomy were performed. It was shown that in order to
      reach the disk center, the entry point had to be more lateral than recommended by
      most authors. Body height, weight and body surface area were not significantly
      correlated to entry point position or penetration angle. In particular, the
      extension of the intervertebral facet joint determined the route of the probe to
      the disk center. Therefore, CT-assisted planning of the instrument route prior to
      percutaneous lumbar diskectomy is helpful in defining the proper entry point and
      penetration angle for safe and effective instrument positioning.

PMID- 8999444
TI  - [CT-guided neurolysis. Status of the technique and current results].
AB  - INTRODUCTION: Both thoracic and lumbar sympathectomy and celiac ganglion block
      could be established as effective methods; side effects are rarely reported. Only
      the high accuracy of CT-guided positioning can make this possible. Severe side
      effects are merely sporadic if the proper technique is applied. MATERIAL AND
      METHODS: We used 21G or 22G fine needles. All CT-guided percutaneous neurolysis
      methods require a proper blood coagulation. Most common CT scanners are suitable
      for neurolysis if there is enough room for maintaining sterile conditions. All
      neurolysis methods involve sterile puncture of the ganglia under local
      anesthesia, a test block with anesthetic and contrast agent to assess the
      clinical effect and the definitive block with a mixture of 96% ethanol and local
      anesthetic. This allows us to correct the position of the needle if we see
      improper distribution of the test block or unwanted side effects. Though
      inflammatory complications of the peritoneum due to puncture are rarely seen, we
      prefer the dorsal approach whenever possible. RESULTS: Seven of 20 legs showed at
      least transient clinical improvement after CT-guided lumbar sympathectomies; 13
      legs had to be amputated. Results of the methods in the literature differ. For
      lumbar sympathectomy, improved perfusion is reported in 39-89%, depending on the
      pre-selection of the patient group. DISCUSSION: It was recently proved that
      sympathectomy not only improves perfusion of the skin but also of the muscle. The
      hypothesis of a steal effect after sympathectomy towards skin perfusion was
      disproved. Modern aggressive surgical and interventional treatment often leaves
      patients to sympathectomy whose reserves of collateralization are nearly
      exhausted. We presume this is the reason for the different results we found in
      our patient group. For thoracic sympathectomy the clinical treatment depends very
      much on the indications. Whereas palmar hyperhidrosis offers nearly 100% success,
      only 60-70% of patients with disturbance of perfusion have benefited. Results in
      celiac ganglia block also differ. Patients with carcinoma of the pancreas and
      other organs of the upper abdomen benefit in 80-100% of all cases, patients with
      chronic pancreatitis in 60-80%.

PMID- 8999447
TI  - [MRI-guided MRI arthrography of the shoulder].
AB  - PURPOSE: To develop an MR-guided technique for joint puncture in MR arthrography
      of the shoulder and to confirm the intracapsular position of the needle tip by
      visualization of the flow of contrast media into the joint. MATERIALS AND
      METHODS: Three unfixed human shoulder joint specimens were examined on a LOT
      unit. The optimal point of entrance and depth for joint puncture were estimated
      by means of MR-compatible markers on the skin. Needle orientation and
      localization of the needle tip (MR-compatible 22-gauge needle) in the shoulder
      joint were monitored by rapid localizer gradient-echo sequences in two or
      thogonal planes. To confirm the intracapsular position of the needle tip, diluted
      gadolinium-DTPA was administered via a long connecting tube and the flow of
      contrast media into the joint was viewed directly on an LCD screen using real
      time MR imaging (local look technique). RESULTS: The MR-compatible markers on the
      skin allowed determination of the optimal point of entrance and estimation of the
      depth for joint puncture. Passive visualization of the MR-compatible needle due
      to spin dephasing and signal loss provided adequate localization of the intra
      articular needle tip position in all specimens, although significant artefacts
      were present on rapid localizer gradient-echo sequences with an increase in width
      of the apparent needle shaft. Real-time MR imaging of the flow of contrast media
      was possible using the local look technique and the LCD screen of the MR unit and
      allowed confirmation of the intracapsular position. CONCLUSION: MR-guided joint
      puncture and real-time MR-assisted contrast media application results in improved
      MR-arthrography and may replace conventional fluoroscopic guidance.

PMID- 8999446
TI  - [Puncture with an open-sided, interventional MRI system. Illustration with a case
      report].
AB  - INTRODUCTION AND METHODS: A 0.5 T open-configuration MR system allows free access
      to the patient via a 58-cm-wide opening on both sides of the machine. A newly
      developed system for needle guidance enables the examiner to perform biopsies in
      combination with real-time imaging and to position laser fibers in the human
      body. For imaging, a 2D gradient echo sequence is used (TR 19 ms, TE 9 ms, flip
      angle 30 degrees FOV 24 x 24 cm, slice thickness 10 mm matrix 256 x 128). The
      acquired images are displayed on two LCD screens localized within the MR system,
      thus allowing an interactive needle guidance. This procedure is illustrated by a
      case report. DISCUSSION: The handling of the system for needle guidance was
      simple, mainly due to a real-time adaption of the scan plane to the needle
      direction. The possibility of multi-angulated approaches makes biopsies of hardly
      accessible anatomic regions feasible. CONCLUSION: We think that MR-guided needle
      positioning will play an important role in combination with thermosensitive
      therapies. Thermosensitivity of MR imaging allows extensive monitoring of such
      interventions.

PMID- 8999448
TI  - [Laser-induced interstitial induced hyperthermia of cerebral tumors with nuclear
      magnetic resonance tomography control].
AB  - PURPOSE: The purpose of our study was to determine the value of MRI in monitoring
      laser-induced interstitial thermotherapy (LITT) of cerebral neoplasms. MATERIALS
      AND METHODS: Sixteen patients with brain tumors were treated with LITT. The laser
      irradiation was performed within the MR unit and monitored with a temperature
      sensitive T1-weighted 2D-FLASH sequence. RESULTS: During irradiation a gradually
      increasing central zone of high signal intensity was surrounded by an increasing
      area of reduced signal intensity. After therapy, the diameter of an enhancing rim
      at the outer border of the peripheral zone indicated total lesion size. On T2
      weighted images the signal intensities were reversed. Total lesion size decreased
      during follow-up. CONCLUSION: MRI is suitable for monitoring LITT. However, the
      role of LITT in the treatment of brain tumors has still to be defined.

PMID- 8999449
TI  - [MRI monitoring before, during and after interstitial laser-induced hyperthermia
      of benign prostatic hyperplasia. Initial clinical experiences].
AB  - PURPOSE: To assess the clinical value of MRI in patients with benign prostatic
      hyperplasia (BPH) before, during, and after interstitial laser-induced
      thermotherapy (LITT) of the prostate. METHODS: Ten patients with symptomatic BPH
      had MRI examinations of the prostate 48 h before and after LITT. Online
      monitoring with MRI at 1.5 T of interstitial Nd:YAG laser energy deposition in
      the prostate was performed in two patients, repeating a T1-weighted FLASH
      sequence (TR 100 ms, TE 5 ms, flip angle 90 degrees) every 20 s. Follow-up MRI
      examinations 2-3 weeks, 6-8 weeks, and 6-12 months after LITT were carried out in
      eight patients, using T2-weighted FSE images and contrast-enhanced T1-weighted SE
      images. RESULTS: The prostate was well delineated in all patients on T2-weighted
      FSE images, with a rather homogeneous peripheral gland and an inhomogeneous
      central gland. Volume measurements yielded reproducibilities of 3.2%-4.7%. Signal
      intensity in the FLASH sequence decreased during LITT, both in the prostate in
      vivo and in specimens of bovine prostate and seminal vesicles in vitro, with
      signal developments running in parallel. Areas of energy deposition and signal
      alteration were not sharply delineated. The latter margin of the laser-induced
      lesions could not be predicted from the FLASH images, while the tip of the laser
      fibre was easily recognized. Contrast-enhanced T1-weighted MR images immediately
      after LITT clearly demarcated low signal intensity laser lesions from high signal
      intensity surrounding prostate tissue. Follow-up examinations showed a decrease
      of 20% of prostate volume over a period of 6-12 months after LITT. Correlation
      between prostate volume development and lesion volume alteration was 0.85-0.90 (P
      = 0.002-0.007) at all follow-up times. CONCLUSIONS: MRI allows rather precise
      recognition of intraprostatic alterations after LITT, including volume changes
      over a period of up to 1 year after therapy that can be predicted immediately
      after LITT. While laser energy deposition in the prostate can be monitored by MRI
      with T1-weighted FLASH sequences as a function of temperature alteration, it is
      not possible to determine the lesion margins immediately from the FLASH images.
      Online temperature development map generation will be necessary to influence on
      going LITT procedures with MRI.

PMID- 8999450
TI  - [Image-oriented planning of minimally invasive conformal irradiation of the head
      neck area].
AB  - Modern imaging techniques are a substantial part of treatment planning for
      minimally invasive radiotherapeutic procedures. The aim is three-dimensional
      assessment of the target volume and adjacent critical structures. In this paper,
      we report on our clinical experience with a precise system for stereotactic image
      correlation. Hereby, the advantages of each imaging modality can be combined.
      Precise immobilization of the patient is a prerequisite. The immobilization
      method has an accuracy of less than 1 mm. This method was evaluated in a clinical
      study in which a tumor control rate of 93% was achieved in patients with brain
      metastases after stereotactic single high dose radiotherapy. This indicated the
      excellent reliability of this treatment planning method. The integration of
      functional image information, such as blood flow or activation of cerebral
      cortical areas, will be evaluated in the future.

PMID- 8999451
TI  - [Image-guided therapy planning for interventional stereotactic therapy of brain
      tumors].
AB  - A treatment planning system for stereotactical neurosurgery has been developed. A
      modular system has been designed which is readily extendable. Different
      modalities of tomography (CT, MRI) can be correlated and presented simultaneously
      in transverse, frontal and sagittal reconstructions. The volumes of interest are
      segmented with respect to the different modalities, and the positions of the
      catheters are defined. The calculation of dose must be adapted to the physical
      requirements of the therapy and is designed as an independent process. The
      calculated data are shown in various presentations. The treatment planning system
      is applied to intratumoral chemotherapy. The drug is encapsulated in small
      carriers for prolonged release and injected via catheters directly into the tumor
      interstitium, bypassing the blood-brain barrier. The dose is calculated using the
      time-dependent, three-dimensional finite elements method. To achieve homogeneous
      temporal and spatial drug distribution it is necessary to use a great number of
      catheters due to the limited diffusion of drug, which is not practical in
      neurosurgery. Therefore this therapy concept is useful for small volumes only.
      Interstitial hyperthermia and brachytherapy, in contrast to intratumoral
      chemotherapy, show successful clinical results.

PMID- 8999452
TI  - [PET studies with C-11 ethanol in intratumoral therapy of hepatocellular
      carcinomas].
AB  - Positron emission tomography (PET) is a noninvasive functional method for the
      study of solid tumor perfusion, metabolism and interaction with different
      therapeutic agents. The aim of the study was the investigation of the metabolism
      of hepatocellular carcinomas (HCC) and the kinetics during a treatment with
      intratumoral ethanol by PET. The ongoing study includes seven patients with
      child. A cirrhosis and HCC (UICC stage III-IVA; tumor size 3-6 cm). Dynamic PET
      studies (60 min) with 18F-fluordeoxyglucose (FDG) were performed prior to therapy
      to assess tumor viability. The evaluation of the FDG data demonstrated a liver
      equivalent uptake in six of the tumors (well and moderately differentiated HCC),
      which were poorly delineated against the normal liver parenchyma. One moderately
      differentiated HCC showed an increased FDG metabolism, indicating no correlation
      between histology and metabolism. A dose of 37-80 MBq 11C-ethanol was applied
      together with a nonlabelled therapeutic dose of the drug via a puncture needle
      positioned under sonography. Five out of seven tumors demonstrated a high 11C
      uptake shortly after the end of the ethanol injection followed by constant 11C
      ethanol concentration during the whole study period of 45 min. The PET data
      demonstrated no significant elimination of the 11C-ethanol from the tumor and no
      accumulation in the surrounding liver tissue. One case showed a decrease of the
      intra-tumoral 11C-ethanol concentration due to a punkture of a tumor vein, and in
      another case the surrounding liver parenchyma demonstrated significant 11C uptake
      in the early phase following paratumoral injection of the drug. In conclusion,
      PET is a useful tool for the study of the mechanism and the kinetics of
      percutaneous intratumoral ethanol injection of HCC.

PMID- 8999453
TI  - [Determination of blood circulation time for optimizing contrast medium
      administration in CT angiography].
AB  - INTENTION: CT angiography of intracranial vascular lesions requires a constant
      and high intra-arterial concentration of the contrast medium over the period of
      data acquisition. The volume of the injected contrast medium can be minimized by
      exact timing of the bolus injection. Non-predictable interindividual variance of
      veno-arterial circulation time, e.g., in patients with impaired cerebral
      hemodynamics after subarachnoidal hemorrhage, requires determination of the
      appropriate prescan delay. METHODS: We used the CT scanner (Philips SR 7000) with
      a low-dose scan parameter to determine the veno-arterial circulation time with a
      bolus injection of 20 ml contrast medium IV and compared these values with the
      results of an algorithm (t = n x 60 x f-1) based on the duration of n = 12 heart
      actions. On CT seven scans (1-s scan time) without table feed were applied at the
      level of the circle of Willis 4 s after the beginning of contrast medium bolus
      injection (5 ml/s). An interscan delay of 4 s was used. A region of interest was
      placed exactly on the most evident part of one of the cerebral base arteries
      contralateral to pathology. RESULTS: In 35 patients we measured circulation times
      between 10 and 25 s, all of which were confirmed by CT angiography, which
      followed. There was no correlation with systolic or diastolic blood pressure,
      heart rate or body length, body weight or body surface. Differences of up to 18 s
      were seen between the measured and calculated circulation times. CONCLUSION:
      Transit time to peak concentration in cerebral vessels following antecubital
      bolus injection of contrast medium cannot be calculated on the basis of
      hemodynamic parameters or body measurement, even in patients without
      cardiopulmonary or occlusive vessel disease. The quick method presented for
      measurement of the veno-arterial circulation time with a test bolus of contrast
      medium using the CT scanner and scan parameters with low-radiation exposure
      provided an exact time setting and saved on the amount of contrast medium needed
      in CT angiography.

PMID- 8999454
TI  - [Incidental CT finding: calcinosis of the anterior eye segment. Senile scleral
      plaques].

PMID- 8999455
TI  - [Mastopathy with atypia (mastopathy III) vs. minimal carcinoma in situ (MCIS)].

PMID- 8999456
TI  - [33rd annual meeting of the Society of Pediatric Radiology. Mainz, 3-5 October
      1996. Abstracts].

PMID- 8999458
TI  - [Half-time of erythropoietin in patients with chronic obstructive pulmonary
      diseases].
AB  - Presence of elevated plasma levels of erythropoietin (EPO) has been reported both
      in polycythaemic and normocythaemic patients with chronic obstructive pulmonary
      disease (COPD). The present study aimed to elucidate in what extent prolonged
      erythropoietin half-life time (T1/2EPO) is involved in the pathogenesis of
      elevated plasma EPO levels in patients with COPD. Seven normocythaemic patients
      (5 men and 2 women) with CODP and 6 healthy controls (4 males and 2 females) were
      examined. In all examined subjects half-life time of erythropoietin was
      determined after i.v. administration of EPO in a dose of 50 U/kg b.m. In COPD
      patients the T1/2EPO value was 5.98 +/- 0.67 hours and did not differ from that
      found in healthy controls (5.87 +/- 0.35 h). Results obtained in this study
      suggest participation of factors other than prolonged half-time of erythropoietin
      in the pathogenesis of polycythaemia in patients with COPD.

PMID- 8999457
TI  - [Borreliosis--Lyme disease--a growing clinical problem].
AB  - Clinical and epidemiological analysis of Lyme disease cases treated at the
      Infectious Diseases Clinic of the Medical University of Gdansk and the District
      Hospital of Infectious Diseases in the years 1993-1995 was done. The results were
      compared to data presented in the literature. The material consisted of 184
      patients, 169 in I stage of the disease and 15 in the II stage. Out of 15 in the
      II stage, 2 patients presented with lymphocytoma benigna cutis, 7 with arthritis
      and 6 with neuroboreliosis. The Lyme disease diagnosis was confirmed with
      positive serological tests in 45% of patients in the I stage and in 100% of
      patients in the II stage. Over the analysed time interval, 1993-1995, the
      incidence of Lyme disease has increased markedly; 1993-38 cases, 1994-50 cases
      and 96 cases in 1995.

PMID- 8999460
TI  - [Effect of treating glomerulonephritis with omega 3 fatty acids for selected
      parameters of hemostasis, blood platelet function and lipid metabolism].
AB  - Disturbances in serum lipids, hemostasis and platelet functions are frequent
      features in some kidney diseases and may contribute to the progression of
      atherosclerosis with its complications. Recently, an attention has been paid on
      beneficial effects of fish oil on serum lipids and hemostasis, and proteinuria.
      The purpose of this work was to assess platelet functions, some hemostatic
      parameters and serum lipids in patients with chronic glomerulonephritis treated
      with Trienyl. The study was performed on 7 patients with glomerulonephritis,
      before, 3 and 6 months following fish oil treatment. A small and nonsignificant
      rise in cholesterol, HDL and LDL was found, whereas triglycerides level fell
      significantly following 3 and 6 months of therapy Fibrinogen concentration was
      lowered significantly 6 months following fish oil administration. Platelet
      aggregation in platelet-rich plasma remained unaltered during therapy, whereas
      platelet responses to ADP and arachidonic acid in the whole blood were inhibited
      after 6 months of the therapy. Unsaturated omega 3 fatty acids in Trienyl alter
      lipid metabolism, platelet/vessel wall interactions and proteinuria and therefore
      might be beneficial in therapy of glomerulonephritis, particularly in combination
      treatment.

PMID- 8999459
TI  - [Analysis of toxicological information rendered by the staff of the National
      Poison Information Center and physicians at the Clinic of Acute Poisoning of the
      Institute of Occupational Medicine in Lodz].
AB  - The article presents structure of toxicological information given by phone to the
      physicians involved in treatment of acute poisonings, private persons the
      services monitoring the working environment. The information comprises data on
      toxic effect on human organism, chemical composition, therapeutic procedure in
      acute poisonings as well as the data on hazards occurring in every day life. The
      consultations chiefly regarded poisonings with drugs, pesticides, alcohols,
      organic solvents and corrosive substances. The analysis has shown that poisonings
      of children aged below 14 years pose a significant problem. Moreover, it has been
      noted that there is a growing demand for toxicological consultations among the
      general population. They play a significant role in education of the society,
      making them aware of the hazards created by various chemicals used in the
      households and occurring in the working environment which contributes to
      promotion of the poisonings prevention.

PMID- 8999462
TI  - [The role of natural growth stimulators in regulation of regeneration processes
      in small intestinal epithelium after irradiation].
AB  - In this paper, basing on recently published data, the influence of growth factors
      on small intestine epithelium regeneration after irradiation is presented. Our
      knowledge of growth control in the small intestine mucosa may become an accepted
      mode of radio-, chemotherapy and the treatment of acute radiation sickness in the
      future. Results of recent studies suggest that there are different factors which
      can modulate the process of epithelium regeneration. Some of them such as
      gastrin, enteroglucagon, CCK, EGF, FGF, TGF and IL-11 are able to enhance this
      process. In addition, other factor-PGE-2 is responsible for not only stimulation
      of small intestine epithelium growth but radioprotection as well.

PMID- 8999463
TI  - [Clinical pharmacology of 2-chlorodeoxyadenosine (Cladribine)].
AB  - 2-chlorodeoxyadenosine (2-CdA) is a simple nucleoside derived from deoxyadenosine
      by substituting chloride for hydrogen in 2' position of the purine ring, which
      renders it resistant to degradation by adenosine deaminase. Many studies have
      revealed high efficiency of 2-CdA in the treatment of lymphoid malignancies.
      Hairy cell leukemia is notably responsive to 2-CdA, with 85% of patients entering
      complete remissions after treatment of this drug.

PMID- 8999461
TI  - [Influence of energy expenditure and other factors on the incidence of arterial
      hypertension in employees with some types of employment in Tychy].
AB  - The aim of the work was to evaluate the incidence of arterial hypertension in the
      inhabitants of Tychy, a city polluted by ecotoxins, in relation to the energy
      expenditure of professional work, in consideration of overweight,
      cholesterolaemia, uricemia, alcohol consumption, age and sex. Investigations were
      carried out on 1964 individuals (1392 men, 572 women) divided in 5 groups with
      different intensity of professional work. Serum uric acid and cholesterol levels
      were determined in all examined persons. Incidence of the obesity was also
      considered. The authors conclude that the risk of arterial hypertension in the
      examined individuals of Tychy is average 17.4% for both men and women, and it
      decreases with enhanced energy expenditure at professional work for men. Arterial
      hypertension appears in subjects from obesity, hyperuricaemia and drinking more
      than 4.0 dl of pure ethanol per week.

PMID- 8999464
TI  - [Clinical and kinetic evaluation of continuous ambulatory peritoneal dialysis
      (CAPD)].

PMID- 8999465
TI  - [Cytokines in systemic lupus erythematosus].
AB  - In systemic lupus erythematosus (SLE) is a disease characterized by B cell
      hyperactivity, autoantibody production and immune complex deposition in vital
      organs. To explain the mechanisms responsible for immune dysregulation in SLE
      cytokines have received increasing attention. This review has discussed a number
      of cytokines which appear to be involved in lupus pathogenesis. Recent studies
      have shown that disease activity and the main symptoms of SLE are associated with
      increasing serum levels of cytokines such as interleukin-(IL)-1, IL-2, IL-6,
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (THF-alpha).
      Constitutive expression and in vitro induction of specific cytokines are also
      aberrant in SLE. The presence of IL-1, IL-6 and IFN-gamma in involved kidneys
      suggests that they have local pathogenic effects. Moreover IFN-gamma, IL-6 and IL
      1 modulate spontaneous IgG production by SLE mononuclear cells. During the next
      several years, the exact role of these cytokine in the pathogenesis of lupus
      become more fully elucidated.

PMID- 8999466
TI  - [Adhesion molecules and their role in pathogenesis of ARDS].
AB  - Adult Respiratory Distress Syndrome appears to develop as the acute lung injury
      in the course of many severe diseases, as the result of damage of alveolar
      capillary barrier. There are many evidences, that neutrophils may participate in
      initiation and contribute to the severity of the syndrome course. Activated
      neutrophils demonstrate high adhesiveness to the endothelium. Leucocyte adhesion
      and further extravasation create the process named the adhesion cascade. In the
      course of this process, the adhesive molecules play the key role. Recent studies
      on animals shown, that anti-adhesive action of monoclonal antibodies and their
      chimeres decrease the degree of injury of alveolar-capillary barrier. Clinical
      observations demonstrate that analysis of dynamics of changes of E, P-selectin
      and ICAM-1 concentrations in the serum of patients with ARDS may be helpful in
      monitoring of the course and treatment of the disease.

PMID- 8999467
TI  - [Consequences of exposure to asbestos dust].
AB  - Mesotheliomas of pleura are neoplasms that rarely occur. Their etiology is
      connected with occupational exposure as well as environmental contact with
      asbestos dust. In this work, two cases of mesotheliomas of pleura are presented:
      first one with occupational exposure, the other one with environmental exposure.
      An increased number of mesothelioma diseases has been emphasised and endangerment
      of inhabitants health living closely to asbestos processing factory as well.

PMID- 8999468
TI  - [Opening of the middle thyroid vein into the vertebral vein in the fetus].
AB  - In the material of 29 human fetuses, of both sexes, without developmental
      anomalies, we investigated by corrosion technique outflow of blood from the
      thyroid gland. On the basis of this study, we noticed in one case the rare
      variation of immediately of the orifice of the middle thyroid vein to the
      vertebral vein. This observation may be applicable of evaluation of phlebograms
      of thyroid gland and surgery of this organ.

PMID- 8999470
TI  - [Nocardia infection].

PMID- 8999469
TI  - [Thrombotic thrombocytopenic purpura successfully treated with plasma exchange].
AB  - This study is a presentation of a case of a 43 year old woman suffering from
      thrombotic thrombocytopenic purpura, the clinical course of which was complicated
      and in which no improvement was observed after fresh frozen plasma transfusions
      and treatment with steroids. The complete clinical and haematological remission
      was obtained only after intensive plasma exchange by therapeutical
      plasmapheresis.

PMID- 8999471
TI  - [On the subject of asthma].

PMID- 8999472
TI  - [The epidemiology and genetics of asthma. I. Descriptive epidemiology and
      analysis of environmental factors].
AB  - Asthma is regarded as a disease with a complex interaction between genetic and
      environmental factors. Since the end of the 1970s and during the 80s the world
      has seen an increase in the prevalence, morbidity and mortality linked to asthma.
      The rapidity of progress of this phenomenon means that it cannot be explained
      only by modification of genetic factors and stresses the preponderance of
      exogenous factors. The purpose of this review is to examine the epidemiological
      knowledge of these environmental factors and of the genetic factors in asthma in
      order to underline how these genetic and exogenous factors interact and modulate
      the occurrence of the asthmatic disease. In the first part of this general review
      we will discuss the epidemiology of asthma in terms of prevalence, incidence,
      mortality, cost and socio-professional and scholastic repercussions and will
      underline for each environmental factor its causal role and/or exacerbation in
      asthma as well as its contribution in the increased prevalence and severity of
      asthma. In the second part of this general view we touch on the epidemiological
      knowledge of the genetics of asthma and of atopy.

PMID- 8999473
TI  - [Gene therapy in oncology: applications to lung cancer].
AB  - Gene therapy defines a new therapeutic avenue whose site of action is at the
      level of the gene itself; viral vectors (adenovirus, retrovirus, herpes virus) or
      non-viral (liposomes, plasmids) enable the transfer of a fraction of DNA
      (transgenic) to the target itself. In this review, we present recently acquired
      data on the mechanisms of oncogenesis and anti-tumor immunity which have enabled
      the application of several therapeutic strategies in oncology; the transfer of
      gene(s), coding for cytokines or for coactivation factors in order to develop
      active immunotherapy; the transfer of suicides genes; the transfer of multidrug
      resistance gene (MDR1); the transfer of tumor suppressor genes or of cDNA coding
      for antisense oligonucleotides in order to correct genomic anomalies which are
      responsible for the malign phenotype. The development of gene therapy demands the
      resolution of a number of technical difficulties such as vectorisation,
      targeting, and the expression of the stability of the trans-gene. Phase 1 trials
      in man have established the innocuity of certain vectors and have confirmed the
      expression of trans-genes (marker genes). Compared to monogenic hereditary
      diseases, the "molecular heterogenetic" of bronchial tumours, the consequence of
      the instability of the genome and the diversity of amplified oncogenes are a
      major difficulty. In addition, each one of these approaches prevents limiting
      factors: for example the exclusive targeting of malign cells is an indispensable
      pre-requisite for the transfer of suicide genes and in the same way the
      expression the tumour in antigens is the pre-requisite for the development of
      active immunotherapy. We report the overall results of applied trials for
      pulmonary carcinomas on murine models and present their applications which are
      underway in men.

PMID- 8999474
TI  - [Evaluation of the inspiratory muscle strength using the nasal pressure of the
      sniff].
AB  - The measurement of oesophageal pressure during maximal sniffs (Poes sniff) is
      useful to assess inspiratory muscle strength. The aim of this study was to
      develop a noninvasive test of inspiratory muscle strength based on the sniff
      manoeuvre. The sniff nasal inspiratory pressure (SNIP) was measured through a
      plug occluding one nostril during sniffs performed through the contralateral
      nostril. In 10 normal subjects and in 12 patients with neuromuscular or skeletal
      disorders, the SNIP reliably reflected the Poes sniff. Nasal mucosa congestion
      was induced in four normal subjects by nebulization of increasing doses of
      histamine. The SNIP accurately reflected Poes sniff when nasal congestion was
      moderate, but failed to do so when congestion was severe. Reference values of
      SNIP were established in a group of 160 healthy subjects aged 20-80 years. For
      both men and women, SNIP was negatively correlated with age, and was similar in
      the sitting and in the supine positions. SNIP was higher than maximal inspiratory
      pressure (P1 max) in most subjects, but the wide limits of agreement showed that
      these two methods are not interchangeable but complementary. The SNIP represents
      a useful noninvasive test of inspiratory muscle strength.

PMID- 8999476
TI  - [Smoking in students in secondary schools in Burkina Faso].
AB  - A multi-centre enquiry in 12 of 30 provinces of Burkina Faso was carried out to
      study smoking in pupils at secondary schools. The prevalence of smoking was 13.6
      per cent. Amongst the smokers, occasional smoking was the most common, involving
      62 per cent. Boys smoked more than girls. The average age of starting smoking was
      early, at 13.4 years. The majority of smokers consumed less than five cigarettes
      a day and the favourite place for consumption was the home of their parents or
      guardian and at school. The determinants of school smokers were above all
      environmental: the influence of friends and advertising. The students showed a
      good knowledge of the harmful effects of smoking. This knowledge was linked to
      their educational level and to their status as a smoker or non-smoker. The
      proportion of pupils who had obtained good results in the term which preceded the
      enquiry was more significant amongst the non-smokers than amongst the smokers. An
      awareness of the significance of smoking amongst pupils by their parents,
      guardians and teachers involves health education and rigorous legislative
      measures on advertising and these would contribute to some reduction in the
      extent of the phenomenon in educational establishments.

PMID- 8999475
TI  - [Occupational respiratory risks in workers exposed to enzymes in detergents].
AB  - The addition of encapsulated enzymes (proteases and lipases) to detergents in
      Morocco dates from 1993. We have carried out a retrospective survey which has
      enabled us to evaluate the prevalence of the clinical symptoms and respiratory
      function problems in two groups, one exposed and the other non-exposed. This
      enquiry which concerns 32 exposed workers and 42 non-exposed consisted of a
      questionnaire (CECA OMS), a chest x-ray and some respiratory function tests. The
      medical study involves a question in the workplace with an evaluation of dust
      levels (weight of dust and enzyme activity). Fifty seven per cent of those
      exposed had clinical respiratory symptomatology against only 7 per cent of those
      who were not exposed. Rhinitis, asthma, cough, chronic bronchitis, eczema and
      conjunctivitis were significantly more frequent in those exposed than in the non
      exposed. Respiratory function was altered in 65.5 per cent of the exposed against
      only 38.6 per cent of those who were not exposed. The overall lung function was
      of an obstructive type. The peak flow (VEMS) were more frequently reduced in
      those exposed (25 per cent) than in the non-exposed (7.14 per cent). These
      anomalies were worst at the end of a day's work. Atopy seems to be a potentiating
      factor. Tobacco interferes significantly in the alteration of respiratory
      function parameters. The enquiry in the work place revealed evidence of
      insufficient means of protection for the work force and elevated levels of dust
      which pass the mean recommended atmospheric values (500 mcg per cubic mm). On the
      other hand, enzymatic activity of the dust collected remained within normal
      limits (< 0.5 GU/m3). It is thus imperative to develop means for collective
      prevention (a more effective encapsulation of the enzymes, work in closed areas,
      ventilation with more effective dust extraction) and individuals (protective
      clothing and specific respiratory masks for the enzymes) to maximally reduce the
      risk.

PMID- 8999477
TI  - [Moderate asthma in adults: diagnosis and management in general medical
      practice].
AB  - Moderate asthma is a frequent disorder in general medicine. In 1990, the British
      Thoracic Society published their first guidelines on the management of asthma.
      Three years later, we have studied, using a questionnaire, the diagnosis and
      therapeutic criteria of moderate asthma used by general physicians, and comparing
      these to the guideline recommendations. Out of 46 physicians questioned in
      Bordeaux, 40 (87 per cent) agreed to participate in the study. Thirty two
      physicians (80 per cent) described as moderate an asthma which was mild according
      to the guidelines; eight physicians (20 per cent) described a moderate asthma
      according to the guidelines; twenty five (63 per cent) considered as severe a
      moderate asthma according to the recommendations, although eleven (28 per cent)
      considered it as moderate and four (10 per cent) did not give an opinion. In
      total, four (10 per cent) judged asthma severity according to the guidelines
      (Group R), twenty one (52 per cent) over-estimated the severity of moderate
      asthma (Group S), and fifteen (37 per cent) gave an inconsistent assessment
      (Group 1). Twenty six (65 per cent) prescribed an association of beta-2-agonists
      and inhaled corticosteroids for moderate asthma. Although most of the questioned
      physicians gave an appropriate treatment for moderate asthma treatment adapted to
      the severity of the situation, their therapeutic approach did not seem to be
      based upon the same criteria than that recommended in the guidelines.

PMID- 8999478
TI  - [Recurrent respiratory infections in patients with chronic obstructive
      bronchitis: medical treatment and costs].
AB  - The objective of this study is to describe usual medical management and costs
      associated with recurrent respiratory infections in subjects with chronic
      obstructive bronchitis in France. A prospective survey was performed in Autumn
      1994 on a national sample of private practice pulmonologists (N = 71). Two
      hundred forty-four patients, presenting at least one infection of the lower
      respiratory tract, were included. Bronchitis was the most frequent acute
      exacerbation observed (94%). Pneumonia concerned 9% of the patients. Biological
      tests, X-rays and pulmonary function tests were prescribed for, respectively, 59,
      65 and 45% of the patients. Following the visit, 15 patients were hospitalized
      (6%). The direct medical cost per acute exacerbation was estimated 3,289 francs
      (1994 value) of which 60% were hospital-related. An average 10.4 day sick-leave
      was prescribed to 21% of patients in employment. For those patients, this sick
      leave was associated to an extra-cost of 1,264-1,876 francs for Social Security
      and of 0-2,553 francs out of pocket per episode varying according to their
      Benefit Regimen.

PMID- 8999479
TI  - [Pseudotumor form of pulmonary nocardia infection (Nocardia nova) in a renal
      transplant patient].
AB  - The authors report a case of pulmonary nocardiosis due to Nocardia nova occurring
      in a smoker who had a renal transplant. A pseudo-tumour was found on a standard X
      ray and computerised tomography did not suggest the diagnosis. Needle aspiration
      under computerised tomographic control enabled a diagnosis to be made.

PMID- 8999480
TI  - [A cause of respiratory distress: eosinophilic pneumopathy due to minocycline].
AB  - We report a case of eosinophilic pneumonia secondary to taking Tetracycline whose
      severity required the use of mechanical ventilation and steroid therapy. On the
      basis of this case, we review the characteristics of drug-induced pneumonia as
      well as the differential diagnosis which are evoked.

PMID- 8999481
TI  - [Pulmonary embolism disclosing activated protein C resistance].
AB  - Resistance to the activation of protein C is a recently discovered constitutional
      anomaly of coagulation which is responsible for thromboembolic events in young
      subjects. We report a case in a 26 year old man who presented with pulmonary
      embolus. Laboratory data was characterised by an absence of any lengthening of
      the activated cephaline time after adding purified activated exogenous Protein C.
      The confirmation of this anomaly is provided by the evidence of a mutation Arg
      506 to Gln of Factor 5. The outcome is favourable with treatment by Heparin then
      by anti-Vitamin K.

PMID- 8999482
TI  - [Unusual spinal and pulmonary metastases].
AB  - We present the clinical and imaging findings of a 72 year old man with lytic
      dorsal bone lesions and a pulmonary spread of nodules (miliary) that were
      mistakenly attributed to a cancerous disease.

PMID- 8999483
TI  - [Cyanosis and multiple pulmonary nodules].

PMID- 8999484
TI  - [Multiple migratory pulmonary opacities].

PMID- 8999485
TI  - [Antineutrophilic cytoplasmic antibodies (ANCA) in respiratory pathology].

PMID- 8999487
TI  - [What is your diagnosis? Ventricular tachycardia with capture beats in
      bradycardiac atrial fibrillation].

PMID- 8999486
TI  - ["Good" and "bad" beta-carotene?].

PMID- 8999488
TI  - [Dentogenous infections: from harmless to life-threatening].

PMID- 8999489
TI  - [Prevention and therapy of post-traumatic disorders from a biopsychosocial
      viewpoint].
AB  - Traumatic events such as accidents, rape or industrial disasters usually have
      biological, psychological and social consequences. Depending on the context and
      the type of trauma, psychiatric disorders may develop; acute stress reaction and
      post-traumatic stress disorder as well as unspecific disorders like depression,
      anxiety and somatoform disorder. In this paper, the traumatic event is understood
      as a potential crisis trigger. A definition of the term crisis is introduced in
      which the concept of identity plays a central role. Five interdependent areas of
      identity are presented: bodily experience, relationships, work and performance,
      material security, and ethical values. Following these five areas, a
      biopsychosocial approach to prevention and therapy of post-traumatic disorders is
      introduced. It is explained how, on the basis of a consistent theoretical
      framework, psychotherapeutic, pharmacotherapeutic, sociotherapeutic,
      physiotherapeutic and other interventions can be used in a multimodal treatment
      conception.

PMID- 8999491
TI  - [Psychiatric emergencies].
AB  - Psychiatric emergencies must not just be seen as catastrophies. They invariably
      represent the nadir of a development which has not been given enough attention
      while it arose. In contrast to a typical medical emergency situation the doctor
      is usually not particularly welcome by the disturbed psychiatric patient and his
      family. This may represent some hardship for the good doctor. When arriving at
      the scene of a psychiatric emergency, an accurate differential diagnosis will be
      of primary importance. Suicidality, disturbances of consciousness, states of
      excitement, dyskinesias and affective crises are the most frequent findings. In
      contrast to a somatic crisis where rapid intervention may be life-saving, it is
      advisable, to take your time and make sure you took everything into account,
      before making a decision. Sometimes the use of medication can dramatically change
      the scene from drama to dialogue. Basically, one has to determine if a
      hospitalization is necessary or not. Two primary concerns have to be looked into
      here: suicidal risk and dangerousness to others. It is good to be aware of those
      situations and diagnoses well known for their high suicidal potential. The
      question which - if any - compulsive measures have to be taken has to be answered
      and acted upon. Unpopular as they may be, they can resolve an extremely difficult
      situation within minutes. Unnecessary hesitation is not asked here for the sake
      of the patient as well as his family. The best way to deal with psychiatric
      emergencies is to avoid them. Looking out for signs and symptoms of a beginning
      psychotic development or suicidal ideation and acting upon it, for instance with
      medication and/or intensifying contacts with the patient are the primary means to
      prevent a crisis. Stopping medication, by patient or doctor, is one of the main
      reasons for psychiatric emergencies. After a psychiatric emergency has evolved,
      it pays out, to carefully analyse its development, the way it was handled and how
      it finally ended. Thus a crisis may, like the Chinese symbol for it with its
      double meaning, evolve to a chance for the patient.

PMID- 8999490
TI  - [Modern tumor therapy as seen in melanoma].
AB  - Modern therapy of melanoma should always consider the prognosis of the disease.
      Primary low-risk melanomas with tumor-thickness below 1 mm can be treated by
      surgery with a safety margin of 1 cm. If the tumor-thickness is more than 2 mm
      the safety margin should be at least 3 cm. After the resection of lymph node
      metastases adjuvant treatment using Interferon-alpha should be considered.
      Palliative therapy of metastases includes surgery, radiotherapy and
      chemoimmunotherapy. Recent progress in understanding the immunobiology of
      melanoma and the development of gene therapy has offered new perspectives for
      future therapeutical intervention.

PMID- 8999492
TI  - [A case of postprandial hypotension in an elderly subject].
AB  - This is a case report of a 74-year old woman who from March 1994 to April 1995
      was admitted to our hospital because of three episodes of syncope. Each general
      physical examination was normal except for a grade 2/6 systolic murmur. No
      abnormalities were disclosed after several resting electrocardiograms and Holter
      monitoring. The Schellong and the tilt tests were normal. During the last
      admission the patient had a syncope 30 minutes after a meal. Blood pressure
      reduction was documented and postprandial hypotension was diagnosed. Postprandial
      decreases in systolic blood pressure in the elderly may predispose the subject to
      symptomatic hypotension and to falls, dizziness, weakness, angina pectoris,
      stroke and syncope. The mechanism of postprandial hypotension is not fully
      understood. It is defined as a decrease in postprandial systolic blood pressure
      of 20 mmHg or more. Because postprandial hypotension is a common problem in
      older, frail, institutionalized patients, all physicians caring for elderly
      patients should be aware of the hypotensive effects of food intake and should
      consider postprandial hypotension in the evaluation of falls, syncope and other
      ischemic cerebral symptoms.

PMID- 8999493
TI  - [The comatose patient: initial considerations and measures].
AB  - The aim of assessing the emergency patient's threshold of consciousness is to
      diagnose and manage reversible and treatable conditions fast and effectively.
      Diagnosis and treatment procedures can be summarized on three levels. First
      assessment and treatment of hypoxia and shock, second: differentiation of types
      of coma, in order to decide further treatment measures and the choice of hospital
      admittance, and third: initiation of antidotes and other appropriate preclinical
      therapies.

PMID- 8999494
TI  - [A case from practice (367). Malignant mesothelioma].

PMID- 8999496
TI  - Current topics in gastroenterology 1995: exploring the jungle. Proceedings of a
      meeting.

PMID- 8999495
TI  - [A case fom practice (368). Pulmonary tuberculosis in AIDS].

PMID- 8999497
TI  - [Liver injury caused by coumarin anticoagulants: experience of the IKS
      (Intercanton Monitoring Station) and the SANZ (Swiss Center for Drug
      Monitoring)].
AB  - Drug-induced liver diseases are potentially avoidable. Hepatotoxic drugs can
      mimic virtually any form of liver disease. Among all voluntary adverse drug
      reaction reports to central registries, 4-7% refer to drug-induced liver
      diseases. We analyze all cases of coumarin-induced hepatic injuries reported on a
      voluntary basis to the Swiss Drug Monitoring Centre (SANZ) and the
      Pharmacovigilance Centre (IKS) from 1981 to 1995. During this period the SANZ
      collected 9720 reports, 674 of which (6.9%) referred to the liver and the biliary
      tract. In only 11 reports an oral anticoagulant was involved. In 8 cases we
      assumed at least a possible causal relationship. 2 more cases were reported
      directly to the IKS. Among these 10 cases 7 were related to phenprocoumon and 3
      to acenocoumarol. In 4 cases elevated concentrations of liver enzymes were
      measured 2-7 days after the beginning of therapy. In the remaining 6 cases the
      clinical picture was so severe that the patients had to be hospitalized. These 10
      cases are discussed and compared with the cases published in the literature.
      According to our data, hepatic disorders induced by coumarin-anti-coagulants are
      rare. If hepatitis is diagnosed in a patient treated with oral anticoagulants,
      the differential diagnosis of a coumarin-induced hepatic injury has to be
      considered. Crossreactions between the coumarin derivatives phenprocoumon and
      acenocoumarol are possible.

PMID- 8999498
TI  - [Ulcer drugs: profile of side effects of proton-pump blockers in comparison to H2
      blockers in the spontaneous reporting system].
AB  - Inhibition of gastric acid secretion by drugs remains the most important rational
      approach to the treatment of acid related diseases. Histamine H2-antagonists and
      more recently the proton pump blockers have become the first line treatment for
      acid peptic diseases. Proton pump blockers bind specifically to the proton pump
      of the parietal cells and thus inhibit the final acid secretion independently
      from the activating stimuli. Because of this specific mechanism fewer adverse
      effects on other systems in the body are expected with proton pump blockers than
      with histamine antagonists. An analysis of the spontaneous reports which the
      Swiss Drug Monitoring Center (SANZ) received from 1981 to 1995 showed striking
      differences in the adverse drug reaction profile: hypersensitivity reactions with
      fever and anaphylactic reactions, liver disorders such as cholestatic hepatitis,
      most with severe progression and requiring hospitalization, as well as endocrine
      disorders were reported more frequently with histamine antagonists, skin
      reactions and joint disorders, however, were reported more often with proton pump
      blockers. Our data also support the conclusion that adverse drug reactions to
      proton pump blockers and histamine antagonists are rare in the spontaneous
      reporting scheme (reporting rate < 1%). There was a somewhat higher rate of
      serious reports with histamine antagonists. These data do not allow conclusions
      concerning long-term effects or effects with larger than recommended dosages.

PMID- 8999499
TI  - [Thromboembolic events in women treated with hormones. Acute cerebrovascular
      thrombosis in 2 young women receiving ovulation inhibitors, and experiences of
      SANZ (Swiss Drug Monitoring Center) 1991-1995].
AB  - We describe 2 young patients with severe cerebrovascular thrombotic events whose
      only risk factor was intake of oral contraceptives. A 41-year-old woman suffered
      thrombosis of the basilar artery and remained disabled with a locked-in syndrome;
      a 23-year-old woman had thrombosis of the sinus sagittalis. These 2 cases and the
      current discussion regarding the use of hormones either as oral contraceptives or
      hormonal replacement therapy with estrogens and/or progestins prompted a review
      of the literature and a review of all spontaneous reports from 1991 to 1995 to
      SANZ (Schweizerische Arzneimittel-Nebenwirkungs-Zentrale), the Swiss Drug Side
      Effects Monitoring Center. The spontaneous reporting under this system does not
      allow conclusions on prevalence and incidence of adverse events. In these 5 years
      33 vascular events associated with different hormones were reported. There were
      28 reports of venous thrombosis of the lower and upper limb or pulmonary
      embolisms, and 5 reports of cerebrovascular complications. In 9 of 33 cases the
      hormones were used as hormonal replacement therapy and in 24 of 33 cases as oral
      contraceptives. In half of these women other risk factors for thromboembolic
      events such as overweight, family history of thrombosis and immobilization were
      known. Complications occurred with different preparations containing different
      estrogens and progestins. According to the literature, third generation
      progestins seem to involve a slightly increased risk of venous thromboembolism
      but a reduced risk of arterial thromboembolic events, which was confirmed by the
      SANZ data (17 of all 24 cases). Increasing age and rising estrogen dosage of oral
      contraceptives are associated with increased risk of vascular events. Although
      thromboembolic events also occur during hormonal replacement therapy with
      naturally occurring estrogens, the prophylactic potential of these drugs with
      regard to osteoporosis and cardiovascular events certainly outweighs this risk.

PMID- 8999500
TI  - [Successful therapy of salicylate poisoning using glycine and activated
      charcoal].
AB  - Acute intoxications with salicylates are common. In a dosage of 150-300 mg/kg
      they are severe, and above 500 mg/kg potentially fatal. To commit suicide 4
      patients ingested 375-460 mg/kg acetylsalicylic acid; 3-8 hours after ingestion
      salicylate blood levels of up to 760 mg/l were observed. The patients were
      treated for a period of 16 hours with oral charcoal and glycine (1 g/kg
      initially, followed every 4 hours by 0.5 g/kg, and 8 g initially, followed by 4
      g, respectively). To increase urinary pH (7-9) they received i.v. NaHCO3. Blood
      levels of salicylic acid including its metabolites dropped initially with a
      virtual half-life of 2-4 hours. 18 hours after hospital admission every patient
      was in good general condition; none of them required hemodialysis. The urinary
      excretion of total salicylate reached only 6-14% of the dose within the first 12
      hours of therapy, clearly indicating the importance of combined therapy with
      glycine and charcoal in achieving a good clinical outcome.

PMID- 8999501
TI  - [Alcohol and drug abuse: a retrospective analysis of incidence in a regional
      hospital 1993-1994].
AB  - This retrospective study analyzes and compares the incidence of admissions for
      alcohol and drug (i.e.: heroin and cocaine) induced diseases to the internal
      medicine service of Locarno Regional Hospital (61 beds plus intensive care unit)
      between January 1, 1993 and December 31, 1994. Of 4038 admissions, 298 (7.4%)
      were related to alcoholism and drug addiction. 4.2% of all hospital days were due
      to alcohol abuse, whereas 3.2% were related to drug abuse (of these 1.8% were for
      HIV-associated diseases and 0.9% for withdrawal treatment). The male/female ratio
      was 3:1 in both groups, the average age of women being significantly lower in the
      alcoholic group (50.5 +/- 14.4 years vs. 58.1 +/- 12.9; p = 0.003). Over 90% of
      the patients with alcohol-induced conditions continued to consume alcohol. On the
      contrary, only 16% of the HIV-positive patients were still drug-addicted. The in
      hospital mortality was 6% (5% in the alcoholic group; 1.6% and 12%, respectively,
      in the HIV-negative and HIV-positive groups of drug addicts). This study confirms
      the high prevalence of diseases related to alcohol and drug abuse. Women are less
      affected, but show complications of alcohol abuse earlier. Despite the HIV
      epidemic in our area, the admissions of alcoholics to the hospital are more
      frequent than those of drug addicts. Most of the drug addicts with an HIV
      associated condition are in remission, whereas alcoholics with alcohol-induced
      diseases continue, for the most part, to be alcohol-dependent.

PMID- 8999503
TI  - [Determination of free PSA in 85 consecutive cases with increased total PSA].
AB  - With a view to a more clearcut discrimination between benign prostatic
      hyperplasia (BPH) and prostate cancer (PCA), an additional measurement of the
      free PSA serum concentration and its ratio to total PSA (f-PSA/t-PSA) were
      determined in sera from 85 consecutive ambulatory patients with a total PSA
      concentration exceeding 4 ng/ml. Results with a ratio higher than 0.16 correlated
      with a high probability of benign disease (BPH), while a ratio below 0.16 was
      less meaningful. Thus, testing of free PSA seems to contribute to reducing the
      number of unnecessary biopsies in patients with elevated PSA.

PMID- 8999502
TI  - [Antiphospholipid antibodies syndrome: follow-up of patients with a high
      antiphospholipid antibodies titer].
AB  - 41 subjects with highly elevated IgG anticardiolipin antibody (aCL) titers (> 30
      GPL-U/ml) were retrospectively evaluated regarding underlying disease, clinical
      symptoms, and in particular the influence of drugs on aCL titer and clinical
      symptoms. Whereas 31/41 (76%) fulfilled the criteria for an antiphospholipid
      antibody syndrome (APS), 10 (24%) did not. About half (47%) of the patients had
      an autoimmune disease (mainly systemic lupus erythematosus). 26 (63%) had had
      recurrent thrombophilic events, 3 (7%) recurrent spontaneous abortions and 10
      (24%) associated thrombocytopenia. 8/34 (23%) subjects followed up over 6-42
      months had a thrombophilic complication again. 6/16 (37%) developed deep venous
      thrombosis in spite of oral anticoagulation (INR 1.5-3.0), one of three under
      acetylsalicylic acid treatment and only one subject without therapy. ACL titer
      decreased (> 12 U/ml) in 20/34 subjects (59%) during the follow-up period, mainly
      in patients under immunosuppressive treatment due to the underlying autoimmune
      disease. In comparison with 5/14 subjects (36%) with consistently high aCL, only
      3/20 (15%) with decreasing aCL developed thrombosis. Patients treated by
      immunosuppressive agents had a higher incidence of decreasing aCL than those
      without. This investigation indicates that a high titer of aCL in asymptomatic
      subjects does not justify prophylactic anticoagulation therapy. However, if a
      history of recurrent deep venous thromboses or pulmonary embolisms is
      established, long-term anticoagulation therapy should be maintained at or above
      the international normalized ratio (INR) of 3. ACL titers in subjects with an
      autoimmune disease may decline, as a result of immunosuppressive treatment or
      otherwise, and this decline is associated with a lower incidence of thrombophilic
      disorders.

PMID- 8999504
TI  - [Complications in the endoscopic polypectomy of colonic adenomas].
AB  - Endoscopic polypectomy is associated with a small but definite risk of bleeding
      and perforation. Patients with large adenomas are thus usually hospitalized for
      endoscopic resection. In order to evaluate whether these procedures can be
      performed in the setting of one day surgery, we retrospectively analyzed the
      complications and results of polypectomy done in the period from 1.1.1990 through
      31.12.1994. Of 1399 colorectal adenomas respected in 680 patients, 385 (28%) were
      larger than 1 cm. Altogether we observed only 3 (0.2%) clinically significant
      complications: bleeding was seen in 2 patients, of whom only one required
      transfusion of one unit. One patient required surgery because of perforation
      after removal of a sessile cecal adenoma with uneventful outcome. These results
      show that endoscopic resection of colorectal adenomas is safe even if the polyps
      are large.

PMID- 8999505
TI  - [Attitude of Swiss Army recruits from Tessin to pain and euthanasia (1992 and
      1995)].
AB  - Nineteen-year-old Swiss Army conscripts were questioned in 1992 (n = 1361) and
      1995 (n = 1050) about their opinions regarding pain and euthanasia. In 1995, 85%
      (1992: 71%) considered pain as a fundamental part of life, 73% (1992: 77%)
      thought that the patient himself should decide how to control pain, and 50%
      (1992: 51%) would accept the idea of euthanasia at the request of a family member
      with an incurable disease and in pain. Significant differences were found only in
      correlation to the degree of religious belief.

PMID- 8999506
TI  - [Acute abdomen and cystic space-occupying lesion in mid abdomen].

PMID- 8999507
TI  - [Guidelines for the handling of antineoplastic drugs].
AB  - Chemotherapeutic drugs are potentially harmful. It is the task of the
      veterinarian to minimize the danger to the staff, the owner and the animal and to
      educate all persons in contact. Potential harm from the use of cytotoxic
      medications can never be completely ruled out. However the adherence to certain
      guidelines can ensure that the risks are minimized. In this article practical
      guidelines are presented and discussed.

PMID- 8999508
TI  - [Traumatic elbow joint luxation in the dog and cat: perioperative findings].
AB  - Thirty-eight cases (24 dogs, 14 cats) of elbow luxation were reviewed. Seventeen
      surgical treatments were necessary either after conservative reduction (14) or
      because conservative reduction was not possible (3). Medial instability of the
      elbow joint due to medial collateral ligamental damage or avulsion of the origin
      of the medial collateral ligament were the major indication for surgery. The type
      and frequency of perioperative lesions as well as their therapeutical and
      prognostical relevance are described.

PMID- 8999509
TI  - [Systems for monitoring animal health in Switzerland].
AB  - Due to the changing conditions of animal production in Switzerland the demand for
      scientifically based animal health information has increased during the last
      years. It has become a central element in animal health policy making. National
      animal health surveillance systems include methods for data collection, analyses,
      interpretation and information distribution. The current Swiss surveillance
      systems are presented. In the future, these systems should be more integrated in
      order to make better use of the available data. The project "Systems for the
      recording of animal health in Switzerland" (SysET) is a proposal how a
      comprehensive animal data base could be developed.

PMID- 8999510
TI  - [Case report: tyrosine deposits].
AB  - Whitish precipitations in three samples of raw cured ham, which appeared in the
      stereomicroscope as piles of crystals, were confirmed as tyrosine crystals.
      Tyrosine is readily soluble in nitric acid (yellowish discoloration) and, after
      addition of potash lye, it precipitates as yellow-orange picrate. Factors that
      influence the formation of tyrosine crystals are largely unknown. In raw cured
      ham of Parma experience has shown that tyrosine crystals are found in ham stored
      for a very long time.

PMID- 8999512
TI  - Chewing the fat.

PMID- 8999511
TI  - Steps to recovery. Researchers finding ways of coaxing spinal nerves to grow.

PMID- 8999513
TI  - [Normal fetal growth profile--a uniform model for calculating normal curves for
      current head and abdomen parameters and long limb bones].
AB  - AIM: Age-related and uniformly defined standard graphs were obtained for the
      fetal parameters BPD, OFD, HC, ATD, ASD, AC, Fe, Ti, Fi, Hu, Ra and Ul. METHODS:
      Data of 2032 healthy pregnant women of sonographically confirmed gestational age
      were used in a prospective cross-sectional study to establish reference charts
      for the fetal head and abdomen and the long limb bones. Only patients with an
      uncomplicated pregnancy were included in the study. The gestational age at which
      the measurements were taken ranged from 12 to 41 completed weeks. All
      measurements were performed as external-to-external measurements. RESULTS: By
      means of a mathematical model age related standard reference ranges were
      calculated on the basis of a single formula. Uniformly well-defined standard
      graphs were obtained for all parameters. All fetal parameters showed a nonlinear
      fetal growth. SUMMARY: Contrary to the common methods of creating reference
      standards by means of high-degree polynomials, the mathematical model presented
      here has the advantage of characterising the course of several parameters on the
      basis of one single formula. This is of great importance for digitising fetal
      charts in commercially available ultrasound machines.

PMID- 8999514
TI  - [Reliability of ultrasound pregnancy screening].
AB  - This study investigates the reliability of ultrasonographic screenings for
      detecting fetal malformations in pregnancy. The data from 1505 screening
      examinations of pregnant women who underwent routine checks at the Department of
      Obstetrics of the University of Vienna, were compared with the anomalies
      diagnosed in the newborn of the same collective. Fetal malformations were
      diagnosed in 28 screening cases. The statistical distribution of these anomalies
      is shown for the different organ systems. In 5 newborn malformations were found,
      which had not been diagnosed sonographically. Another 23 newborn had minor
      malformations in regions that are not included in the routine screening
      ultrasound. The results show a high accuracy of the sonographic screening
      examination, with the exception of the median facial region and the large vessels
      of the base of the heart. The fact that not all of the cardiac malformations were
      diagnosed prompts the performance of an extended sonographic inspection of the
      fetal heart within the framework of routine screening.

PMID- 8999515
TI  - [Measuring amniochorionic membrane thickness with high frequency ultrasound].
AB  - The postpartal thickness of the amniochorionic membrane was measured by means of
      20 MHz ultrasound after 28 inconspicuous deliveries in the course of a
      prospective study. The aim of our investigation was to determine the thickness of
      the amniochorionic membrane using high frequency ultrasound and to evaluate the
      results for a statistical correlation with fetal and maternal parameters. The
      data obtained were compared with histological sections for measurement accuracy
      using a linear regression analysis method. Membrane thickness of the total study
      group was 0.83 +/- 0.11 mm (0.72-1.08 mm). Based on a statistical comparison with
      the histological sections, the high frequency ultrasonographic examination was
      shown to be highly reliable with a correlation coefficient of r = 0.96 (p <
      0.0001). Results obtained by ultrasonography were correlated with maternal
      (gestational age, patient age, parity) and neonatal (size and weight at birth,
      sex, placental weight, Apgar 1/5/10) parameters by means of linear regression
      analysis. There was a statistically significant correlation between parity and
      membrane thickness (r = 0.485, p < 0.05). There was also a correlation of Apgar
      scores at 5 minutes post partum (r = 0.485, p < 0.05). We were able to
      demonstrate that the measurement of membrane thickness by ultrasound is an
      objective and reliable method and may be a gain to prenatal diagnostics when used
      in vivo.

PMID- 8999517
TI  - [Ultrasound "screening examination" of the abdomen: of value or senseless?].
AB  - Screening examinations are diagnostic procedures without an individual indication
      with the purpose to detect a possible disease in an early, asymptomatic stage.
      Primary sonographic screening of the abdomen in individuals without any signs or
      symptoms of abdominal disease cannot be recommended. Secondary screening
      (sonographic examinations of the total abdomen in patients with unspecific
      symptoms) and to examine the remaining abdominal, pelvic and retroperitoneal
      organs which are not needed to answer the specific diagnostic question are
      procedures of doubtful benefit. However, ultrasound is recommended for specific
      screening programs, i.e. tumour detection or diagnosis of aneurysms, in those
      subpopulations with a high prevalence for the specific disease.

PMID- 8999516
TI  - [Doppler ultrasound in cases of Rhesus incompatibility. Effect of intravascular
      punctures with or without transfusion on feto-placental Doppler blood flow
      velocity curves].
AB  - OBJECTIVE: To investigate the influence of cordocentesis with or without blood
      transfusion on umbilical and fetal blood flow characteristics. METHODS: Of 42
      pregnant women suffering from Rh. incompatibility 15 had a puncture of the
      umbilical cord for diagnostic reasons only. In 27 cases a total of 86 punctures
      was done for blood transfusion. Fetal heart rate, umbilical artery A/B Ratio and
      Pulsatility Index (PI) in the fetal aorta were measured before and after
      cordocentesis in all cases having or having not a transfusion. RESULTS:
      Diagnostic and therapeutic cordocentesis resulted in a slight decrease of
      peripheral resistance. Significant differences were only observed in cases with a
      haematocrit < 20% compared to cases with values > 40% or if the final haematocrit
      after transfusion resulted in a value of < 30%. CONCLUSION: The decrease
      peripheral resistance in cases of therapeutic cordocentesis can be attributed to
      the increase in blood volume and sufficient oxygenation of blood improving fetal
      perfusion. Doppler sonography is not helpful in the clinical management of red
      blood cell immunisation.

PMID- 8999518
TI  - [Ultrasound manifestations of abdominal lymphomas. An overview].
AB  - Abdominal sonography is now the most frequently used screening method for the
      detection of abdominal lymph node enlargement. For proper classification, size,
      localisation and infiltration pattern must be known. The definitive determination
      whether lymph nodes are benign or malignant cannot be made by the size of the
      lesion alone. The localisation (parietal/visceral) of enlarged lymph nodes has
      been shown to be of significance in the staging of abdominal carcinomas.
      Different infiltration patterns (diffuse small nodular, focal small nodular,
      focal large nodular, bulky formations) show the broad spectrum of abdominal
      lymphomas detected by ultrasound. Knowledge of these different infiltration
      patterns together with clinical information often helps to discriminate between
      lymph node enlargement caused by inflammation, metastasis, or malignant lymphoma.
      The definitive diagnosis is made via laparotomy, ultrasound guided biopsy or
      sonographic follow-up studies.

PMID- 8999519
TI  - [Ultrasound anatomy of the spinal canal of the lumbar spine. Results ofan
      experimental study and report of initial clinical applications of intraoperative
      ultrasound in nucleotomies].
AB  - Results of an Experimental Study and Report of Intraoperative Application: AIM:
      Intraoperative sonography has been used in neurosurgery (especially in tumors)
      and in traumatology (assess reduction of dorsal vertebral body fragments). This
      study was performed to determine the value of sonography in detecting vertebral
      disc tissue. RESULTS: We examined 6 specimens of the Lumbar spine using the
      extended flavectomy approach. We found that sono-anatomy was reproducible and
      that the assessable area was large enough to make sonography useful for detection
      of sequesters. Dislocated vertebral disc tissue could be differentiated clearly
      from original disc tissue and from other intraspinal structures. In 6 of 8 cases
      of intraoperative sonography in nucleotomies we were able to evaluate intraspinal
      and intraforaminal structures. The complete removal of the detected prolapses
      could be documented. In 2 cases the examination failed because the probe had a
      too large diameter and could not be pushed down between the spinous processus and
      the wound distractor to the extended flavectomy. CONCLUSIONS: Sonography allows
      one to document complete resection of disc herniations. Limitations of the method
      are due to technical problems.

PMID- 8999520
TI  - [Comparison between current and high resolution ultrasound for diagnosis of
      breast lesions].
AB  - AIM: To assess the value of high-resolution ultrasound in the diagnosis of breast
      lesions. METHOD: Fifty women with a clinically suspicious breast mass were
      examined with mammography, conventional and high-resolution sonography.
      Ultrasound was performed with a linear-array 7.5-mHz transducer and an annular
      array 13.0 MHz transducer. RESULTS: Histology showed carcinoma in 28 patients,
      fibrocystic changes in 20 and fibroadenoma in 2. High-resolution ultrasound
      characterized 18 lesions more accurately than conventional ultrasound, including
      13 carcinomas, 3 fibrocystic changes and 2 fibroadenomas. The size of 8
      carcinomas was measured more accurately with high-resolution ultrasound than with
      conventional ultrasound. CONCLUSION: High-resolution ultrasound is more valuable
      in the differentiation and size determination of breast lesions than conventional
      ultrasound.

PMID- 8999522
TI  - [Doppler and duplex diagnosis of non-arteriosclerotic vascular diseases. Congress
      report of the Summer Congress of the Professional Circle for Vascular Diagnosis
      of DEGUM. 1995 Summer Congress].

PMID- 8999521
TI  - [Malignant melanoma of the gallbladder].
AB  - A 75 year woman developed a primary malignant melanoma of the gallbladder. The
      patient presented with abdominal pain in the upper right quadrant typically seen
      in acute cholecystitis. Neither intravesical concretions nor cholestasis was
      seen. Ultrasound demonstrated hyperechogenic intraluminal "school of fish"
      reflections, which are typical for metastatic melanoma to the gallbladder.
      Intravesical fluid collection was not present. The tumor did not expand past the
      wall of the gallbladder. The main sonographic features are hyperdense
      intraluminal strands of tumor and the lack of fluid. Computed tomography showed
      solid intraluminal masses with hypodensive and partially hyperdensive reticular
      structure.

PMID- 8999523
TI  - Approaches to AIDS research.

PMID- 8999524
TI  - Swedish biomedical research funding.

PMID- 8999525
TI  - Responsibility of co-authors.

PMID- 8999526
TI  - Breast-implant ruling sends a message.

PMID- 8999527
TI  - Panel urges cloning ethics board.

PMID- 8999528
TI  - Drug industry misses target for funding work on campus.

PMID- 8999529
TI  - New funds plant seeds for genome research effort.

PMID- 8999530
TI  - The many faces of WAS protein.

PMID- 8999531
TI  - Evolutionary psychologists look for roots of cognition.

PMID- 8999532
TI  - Researchers construct cell look-alikes.

PMID- 8999533
TI  - New knockout mice point to molecular basis of memory.

PMID- 8999534
TI  - Pax polio.

PMID- 8999535
TI  - Asthma: an epidemic in the absence of infection?

PMID- 8999536
TI  - There are GAPS and there are GAPS.

PMID- 8999537
TI  - Continuous innovation in health.

PMID- 8999538
TI  - AIDS: the process of discovery.

PMID- 8999539
TI  - AIDS: the process of discovery.

PMID- 8999540
TI  - Neurons and reaction times.

PMID- 8999541
TI  - Neurons and reaction times.

PMID- 8999542
TI  - Neurons and reaction times.

PMID- 8999543
TI  - NIH, Hopkins team up on genotyping.

PMID- 8999544
TI  - Wide use of rabbit virus is good news for native species.

PMID- 8999545
TI  - Opening the way to gene activity.

PMID- 8999546
TI  - The year of the dendrite.

PMID- 8999547
TI  - Neuroscience. More than just frequency detectors?

PMID- 8999548
TI  - Activation of interferon-gamma inducing factor mediated by interleukin-1beta
      converting enzyme.
AB  - The interleukin-1beta (IL-1beta) converting enzyme (ICE) processes the inactive
      IL-1beta precursor to the proinflammatory cytokine. ICE was also shown to cleave
      the precursor of interferon-gamma inducing factor (IGIF) at the authentic
      processing site with high efficiency, thereby activating IGIF and facilitating
      its export. Lipopolysaccharide-activated ICE-deficient (ICE-/-) Kupffer cells
      synthesized the IGIF precursor but failed to process it into the active form.
      Interferon-gamma and IGIF were diminished in the sera of ICE-/- mice exposed to
      Propionibacterium acnes and lipopolysaccharide. The lack of multiple
      proinflammatory cytokines in ICE-/- mice may account for their protection from
      septic shock.

PMID- 8999549
TI  - Reverse transcriptase fidelity and HIV-1 variation.

PMID- 8999550
TI  - Reverse transcriptase fidelity and HIV-1 variation.

PMID- 8999551
TI  - Reverse transcriptase fidelity and HIV-1 variation.

PMID- 8999552
TI  - Proceedings of the roundtable of experts in surgery blood management. Vienna,
      Austria, April 7-9, 1995.

PMID- 8999554
TI  - [Thoracoscopic major pulmonary resection--pro and con].
AB  - The first reports of thoracoscopic video-assisted procedures are from 1993. The
      main reason for this new techniques was that they allow the performance of
      standard thoracic surgical procedures in a less invasive ways. The operation
      trauma is minimalised that could be a cause not only of postoperative pain but
      often also of chronic future problems. The other advantages are the shortened
      hospitalisation time and earlier end of disablement. On the other hand there are
      many objective arguments against here. Firstly, the operative technique is not
      standardised and thoracoscopic lobectomy and pneumonectomy are performed by many
      modified methods. No regular randomised studies are available that could confirm
      the positive contribution of thoracoscopy in these cases. It is possible to
      perform classic thoracotomy by very careful way saving muscles and contemporary
      observing the requirement of safe operation and to attain the maximally possible
      result. Resuming information from written and verbal reports in last 3 years we
      have necessary the impression that the main reason for thoracoscopic reactions
      was to demonstrate the technical feasibility of this operation which is entirely
      insufficient reason for acceptance of this technique. Authors suggest that
      thoracoscopy is in experienced hands and adequately equipped workplaces an
      accurate and safe method for the diagnosis and in some cases also for therapy of
      hemodynamic stabile patients with thoracic trauma.

PMID- 8999553
TI  - [Video-assisted thoracic surgery--lobectomy, pneumonectomy].
AB  - Pneumonectomy performed by the V.A.T.S. method-Video Assisted Thoracic Surgery
      calls for great skill, concentration and experience of the surgeon and puts
      greater demands on him than classical surgery. Minithoracotomy (5-10 cm) combined
      with videothoracoscopy have the joint advantages of miniinvasive operation and
      safety and radicality of the operation. During surgery lymphadeaectomy can be
      performed, it is possible to suture injured arteries or veins. Postoperative
      recovery is markedly better after V.A.T.S. than after conventional surgery. In
      the group of the first 11 V.A.T.S. lobectomies and one V.A.T.S. pneumonectomy the
      authors recorded a very low morbidity and zero mortality. The patients usually do
      not suffer from postoperative pain and rehabilitate well. The easier, less
      painful postoperative course is associated with earlier discharge, rapid
      convalescence and early return to work. V.A.T.S. is, no doubt, a benefit for the
      patient with regard to the postoperative response and course of recovery.

PMID- 8999555
TI  - [Trauma and emergency thoracoscopy].
AB  - Authors present their first experience with urgent videothoracoscopy in
      polytraumatism and in isolated thoracic trauma patients. During the prospective
      study in 1993-1995 thoracoscopically was treated 41 (18%) from 229 multiple
      trauma patients including thorax trauma, hospitalised in our Institute.
      Thoracoscopy underwent 62 (4%) from 1452 patients with simple thoracic trauma.
      Thoracoscopy has been indicated above all for continued bleeding into peritoneal
      cavity, for suspected diafragmatic injury and for the diagnosis and treatment of
      posttraumatic complications. Authors suggest that thoracoscopy is in experienced
      hands and adequatelly equipped workplaces an accurate and safe method for the
      diagnosis and in some cases also for therapy of hemodynamic stabile patients with
      thoracic trauma.

PMID- 8999556
TI  - [A modified approach in laparoscopic cholecystectomy].
AB  - The author gives an account of his experience with the insertion of trocars
      during laparoscopic cholecystectomy. It leads to a better cosmetic effect of the
      operation. Careful selection of patients before surgery prevents possible
      complications. The described procedure is suited only for an experienced surgical
      team which performs laparoscopic operations as a matter of routine.

PMID- 8999558
TI  - [Hernia operations using synthetic materials].
AB  - The authors present an account of their experience with surgery of inguinal and
      ventral hernias using synthetic material and Lichtenstein's or Gallie's method.
      The group of 133 patients comprises 108 patients with hernia in the area of the
      inguinal canal operated by Lichtenstein's plastic operation and 25 patients with
      a ventral hernia operated by Gallie's method. The author mentions the number of
      complications and relapses in the group. The advantage of these methods is
      according to the author the small number of relapses, relatively easy surgical
      technique and easy postoperative course which in inguinal hernias makes it
      possible to use local anaesthesia and perform the operation in the out-patient
      department.

PMID- 8999557
TI  - [Personal experience with the Lichtenstein surgical method in recurrent abdominal
      hernia].
AB  - The authors present a group of 21 patients treated with the method of
      Lichtenstein with the use of polypropylene mesh Prolen. They used the method of
      an "inlay" mesh for recurrent groin and epigastric hernias, mostly by men. The
      men:women ratio was 19:2. They emphasise better healing, early recovery to work
      and almost no wound infection by use of this method.

PMID- 8999559
TI  - [Tuberculosis of the stomach].

PMID- 8999560
TI  - [Boerhaave's syndrome--case report].

PMID- 8999561
TI  - [Neurinoma of the stomach].

PMID- 8999563
TI  - [Profession and certification].

PMID- 8999562
TI  - [Treatment of distal forearm fractures using external fixation].
AB  - The author presents a group of 37 patients with fractures of the forearm treated
      by the method of external fixation. Mostly closed fractures of the distal radius
      were involved which could not be stabilised conservatively by plaster fixation.
      The method was however also used in open fractures of the forearm and
      pseudoarthroses at this site. Practically always a closed reposition of the
      fracture was made, in some cases supplemented by percutaneous transfixation of an
      unstable fracture by a Kirschner wire.

PMID- 8999564
TI  - [Neonatal care--do we know enough about the consequences?].

PMID- 8999565
TI  - [The Nitter cure--still an eye of the storm?].

PMID- 8999566
TI  - [Differentiated treatment of wrist injuries].

PMID- 8999567
TI  - [Unstable fractures of the distal radius. External fixation or percutaneous
      pinning?].
AB  - The results of treatment for distal radial fractures of types Older 3 with more
      than 5 mm shortening and Older 4 were studied in a prospective randomized series
      of 41 patients with regular follow-up to six months after operation. The patients
      were treated with closed reduction under anaesthesia and either external fixation
      ad modum Hoffman or percutanous pinning and a plaster cast for six weeks. Both
      treatment groups achieved a clinically and radiologically good result without any
      significant difference. There were no infections, and except for one patient with
      persistent signs of mild reflex dystrophy we experienced no serious
      complications. Owing to simplicity and treatment costs we generally prefer
      treatment by pinning and plaster cast.

PMID- 8999568
TI  - [Leakage of cerebrospinal fluid. Diagnosis and treatment].
AB  - Leakage of cerebrospinal fluid may occur after fracture of the skull base or
      after surgery on the skull base, nose, or paranasal sinuses. Further causes of
      cerebrospinal fluid leakage are tumours and malformations. It may also occur
      spontaneously. We describe four case reports illustrating diagnostic and surgical
      problems. Cerebrospinal fluid oto- and rhinorrhoea should be suspected in cases
      of recurring purulent meningitis. Immunologic demonstration of beta(2)
      transferrin in secretions from the nose and ear is a diagnostic sign of
      cerebrospinal fluid or perilymph. Digital subtraction cisternography, CT
      cisternography, and flow-sensitive magnetic resonance imaging are sensitive
      methods for localising dural leakage. Frontal craniotomy has been the traditional
      surgical approach. The recent involvement of transnasal endoscopic sinus surgery
      and microsurgery has made it possible to treat cerebrospinal fluid oto- and
      rhinorrhoea with a high degree of success and less operative morbidity.

PMID- 8999570
TI  - [Neurofibromatosis type I in Norway. A clinical prevalence study based on a small
      project].
AB  - Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder that
      mainly affects the skin, the nervous system and the skeleton. An incidence of
      1:4,000 gives approximately 1,100 patients in Norway. At Frambu we concluded a
      model project for three years to achieve better care from the medical,
      psychosocial and educational aspects. We also included a prevalence study of
      symptoms and complications in 129 patients. We found a complication rate
      remarkably like that found in previous prevalence studies, despite the fact that
      many of our patients were ascertained to be relatives of affected children, and
      were undiagnosed until the child was examined. Our project showed that, because
      neurofibromatosis is a multifaceted disorder, a team approach involving health
      workers and teachers is needed for better care of affected children.

PMID- 8999569
TI  - [The influence of psychological factors on the immune system and immunological
      diseases].
AB  - During the last 10-20 years it has become clear that the immune system not only
      protects the individual against potentially harmful intruders but also interacts
      with both the nervous and endocrine systems. Today we know that immune competent
      cells have receptors for hormones and neurotransmitters, and that cytokine
      receptors are expressed in certain areas of the brain. Furthermore, in many
      animal models immune suppression has been induced by classical conditioning.
      Several in vitro studies have shown signs of reduced immunity in individuals
      during acute and chronic stress. Some studies have also indicated that chronic
      stress may increase the risk of infections and cancer. On the other hand, various
      psychotherapeutic techniques appear to strengthen the immune system. As for
      immunological disease, we know that psychological factors are important in the
      case of allergic asthma. Moreover, serious life events prior to onset of disease
      are reported more frequently by seronegative than by seropositive rheumatoid
      arthritis patients. Prospective studies have shown that psychotherapeutic
      intervention can reduce disability in rheumatoid arthritis patients, but disease
      activity is diminished only rarely.

PMID- 8999571
TI  - [Acoustic rhinometry. A new method for objective assessment of the nasal airway
      dimensions].
AB  - Acoustic rhinometry is a new and simple method for assessment of nasal airway
      dimensions. An audible sound signal generated at the bottom of a tubular probe is
      transmitted into the nasal cavity via an anatomically fitted nosepiece. An area
      distance relationship describing the airway geometry is created by comparing the
      incident and the reflected sound signal. The technique is quick, accurate,
      reproducible, non-invasive, has no adverse effects, is independent of airflow,
      and requires minimal co-operation. Several recent studies have established
      acoustic rhinometry as an important investigative tool in rhinology. It is well
      suited to illustrate normal physiology of the nasal mucosa, to document
      deleterious effects of exposure to irritants and to monitor the effect of
      surgical and medical therapy. A newly developed miniprobe has, in our experience,
      proven to be uniquely suited for studying the nasal airways of infants and small
      children. Considering its advantages, acoustic rhinometry deserves an important
      position in rhinological research and practice.

PMID- 8999572
TI  - [From spas and convalescent homes to retraining institutions].
AB  - The traditional types of health care institutions, the spas and convalescence
      homes, were reorganised in Norway in 1992 to become retraining units group I and
      group II. The new regulations demanded that the institutions should upgrade and
      strengthen their treatment facilities. The physician in charge of group I
      institutions has to have rheumatological or physical medical qualifications, and
      the institution itself has to have sufficient nursing and other medical staff to
      be able to treat patients in need of a higher level of therapy than required by
      patients at group II institutions. A survey of the institutions concludes that
      most of them now conform with the new regulations.

PMID- 8999573
TI  - [A changing panorama of cerebral palsy? A population-based study of children born
      during the 20-year period 1970-89].
AB  - In a population-based study cerebral palsy was diagnosed in 110 cases (2.4 per
      1,000) among live born children with birth weight > or = 500 g (N = 45,976)
      during the 20-year period 1970-89 (cerebral palsy cases with a postneonatal
      etiology excluded). The incidence of cerebral palsy showed a linear declining
      trend from 2.8 per 1,000 in the first five-year cohort born 1970-74 to 2.0 per
      1,000 in children born 1985-89 (p = 0.17). 15.9% of the decline in incidence of
      cerebral palsy from the first to the second ten-year cohort could be explained by
      a decreasing rate of low birth weight (500-2,499 g) in the population, from 4.2%
      1970-79 to 3.8% 1980-89 (p < 0.05). The neonatal mortality rate declined
      significantly from 7.2 per 1,000 in the first to 3.9 per 1,000 in the last ten
      year cohort respectively (p < 0.01). More children with cerebral palsy born in
      the ten-year period 1980-89 were treated with mechanical ventilation in the
      neonatal period (13/46; 28.3%) than such children born in the ten-year period
      1970-79 (4/64; 6.3%) (p < 0.01). The results contrast with the traditional
      findings of a higher incidence of cerebral palsy incidence following improved
      survival of infants with low birth weight. Our results may reflect a more
      integrated development of perinatal care. Research on ways of preventing low
      birth weight may allow us to lower the incidence of cerebral palsy still further.

PMID- 8999574
TI  - [Treatment of supraventricular tachycardia in children].
AB  - Although young infants may have severe symptoms from supraventricular tachycardia
      the majority responds to treatment. In 60-90% of the infants the arrhythmias
      disappear within 6-12 months, whereas in older children the supraventricular
      tachycardia tends to reoccur. Our recommended acute treatment in infants less
      than six months of age is to emmerse the face in cold water, but adenosine should
      be used for pharmacological termination of supraventricular tachycardia in all
      age groups. If this fails, direct current cardioversion should be applied without
      delay. Intravenous verapamil should not be used, however, in infants for
      termination of supraventricular tachycardia. Flecainide can be used for acute and
      prophylactic treatment.

PMID- 8999575
TI  - [Analgesic effect of ketamine in a patient with neuropathic pain].
AB  - We report the effect of a single daily dose of ketamine in a 54 year old woman
      with fibromyalgia and severe post-traumatic neuropathic pain. A number of
      different approaches for pain relief had been tried with little effect. An
      intramuscular test dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg midazolam
      lead to analgesia which lasted for almost two days. Long-term analgesia was also
      obtained by 250 mg/kg ketamine hydrochloride taken orally in the form of capsules
      every night at bedtime. The patient has now used this dose for nine months.
      Ketamine is an NMDA receptor antagonist. A single sub-anaesthetic dose of
      ketamine causes a long-term depression of pain intensity in some, but not in all,
      patients suffering chronic pain. This effect is distinctly different from the
      short-lasting (10-30 min) analgesic effect in cases of acute nociceptive pain.
      The long-term depression of the intensity of chronic pain states may be due to a
      reversal of NMDA receptor-dependent long-term potentiation of synapses in central
      pain pathways. By giving ketamine as a single dose at night the mental side
      effects are reduced or avoided.

PMID- 8999576
TI  - [Perceived access to alcohol among lower secondary school students. A
      longitudinal study].
AB  - In Norway the law forbids drinking of alcohol before the age of 18 years. In
      spite of this, a large portion of Norwegian under-aged adolescents report
      drinking alcohol. A two-year prospective cohort study was conducted to
      investigate perceived access to alcohol in a representative sample of 7th grade
      students (13 years old) in the county of Hordaland, Norway (N = 861). "Getting
      older friends to buy alcohol", "given alcohol by friends", and "taking at home
      without permission" were the most frequently mentioned sources of alcohol both at
      baseline and at follow-up among both drinking and non-drinking students. Among 15
      year old boys who reported drinking alcohol, 21% said that they would buy the
      alcohol themselves. Perceived access to alcohol significantly predicted the
      reported frequency of alcohol use two years later, even when controlled for
      baseline alcohol consumption and perceived social norms among parents and
      students of the same age. It is recommended that parents be advised to reduce
      their children's access to alcohol at home, and that alcohol prevention efforts
      targeting older adolescents should include information on the negative
      consequences of providing alcohol to minors. Furthermore, the current sales laws
      should be more stringently enforced.

PMID- 8999577
TI  - [General practice--quo vadis?].

PMID- 8999578
TI  - [The committee of physicians--an important part of quality assurance?].

PMID- 8999579
TI  - [Do you treat your vitamin B12-patients correctly?].

PMID- 8999580
TI  - [Population responsibility in general practice].

PMID- 8999581
TI  - [Electronic records--what now?].

PMID- 8999582
TI  - [Physicians and the quality revolution in Norwegian health care services].

PMID- 8999583
TI  - [Every idiot can become a director].

PMID- 8999585
TI  - [The Internet as a communication medium in veterinary medicine].
AB  - Medicine is based on expert experience and expert knowledge. One of the newest
      means to exchange up-to-date information is the Internet, the so-called
      information highway. Among academic institutions in Germany, transferring
      information over this world-wide communication network has become increasingly
      important, particularly concerning national and international cooperations in
      science and education. The acceptance has improved with new user-friendly
      graphical computer applications. The internet is regarded as a milestone on the
      way to the information society. In this report, we will present an overview of
      resources and services relevant to veterinary medicine available in the
      international data-network free of charge.

PMID- 8999584
TI  - [Experience with the use of a blood culture system for demonstration of
      clinically relevant bacteria in veterinary medicine diagnosis].
AB  - 268 diagnostic samples from dogs, cats, horses and cattle were examined in a
      commercially available blood culture system. Samples of blood, liquor, ascites,
      thorax punctate, synovia and urine were examined with a blood culture system
      (Oxoid) over a period of two years in cooperation with the veterinary clinical
      institutes of internal medicine and surgery, Ludwig-Maximilians-University,
      Munich and different veterinarians. It was shown that this blood culture system,
      which has been initially developed for the requirements of human bacteriology,
      can be used for isolation of clinical important microorganisms in veterinary
      medicine. In 29% of examined samples isolation of bacteria was possible. Even
      bacteria, which are not often cultivated and bacteria, which could not be
      identified biochemically, could be isolated. Because of experience in human
      bacteriology and in conclusion of our results, the use of blood culture systems
      can be recommended for veterinary diagnosis, in particular when sepsis is
      suspected.

PMID- 8999586
TI  - [Animal husbandry and hunting in the neolithic age as an example of animal
      remains Pestenacker (Lkr. Landsberg am Lech) settlement].
AB  - In Pestenacker (Lkr. Landsberg am Lech) archaeological excavations are done by
      the Bayer. Landesamt fur Denkmalpflege since 1988 in a neolithic settlement,
      which is to be dated in the Altheimer Kultur. Dendrochronological datation
      indicates a beginning of settling in 3496/95 BC. The settlement is located below
      the border of a riss-glacial terrace beside a brook and shows a regular ground
      plan. Because of the high water level there is an excellent preservation of
      organic materials and bones. The osteological investigation of the animal bones
      shows data of the holding of domestic animals, the consumption of meat and the
      value of hunting. The biological analysis points out the reconstruction of the
      surrounding landscape and biotops. The archaeological investigation, a mapping of
      the distribution of the bones, shows the homework.

PMID- 8999587
TI  - [Clinical case. Cairn terrier, female, aged seven].

PMID- 8999588
TI  - [Use of visual methods (sonography/endoscopy) for the diagnosis of a webbed teat
      in cattle. A case report].
AB  - The use of visual methods (sonography/endoscopy) for the diagnosis of a webbed
      teat in a cow with particular consideration of differentiation from a teat
      fistula is reported. The sonographical and endoscopical investigation of a webbed
      teat is evaluated concerning its gain of information in comparison to classical
      diagnostic procedures.

PMID- 8999589
TI  - [Real-time ultrasonic pregnancy diagnosis (B-mode) in sheep. 1. Frequent
      examinations during the first month of pregnancy].
AB  - Transrectal ultrasonography was performed on 63 ewes (four breeds) to determine
      the earliest day at which pregnancy, the first embryo, the number of embryos, the
      embryonal heartbeat and placentoms could be detected. The ewes were examined at
      intervals of two to three days on day 12/13 to 30 post breeding. An Aloka SSD 500
      ultrasound unit was used with a 5-Mhz probe. The diagnosis of the pregnant ewes
      took place on day 17.6 +/- 1.8 p.c. The first embryo was detected on day 20.5 +/-
      1.9 p.c., but not all of the embryos were counted accurately until day 26. The
      heartbeat of the embryos was detected on day 22.9 +/- 2.9 p.c. and placentoms on
      day 27.6 +/- 2.4 p.c. The influence of the breed on the results will be
      discussed. The proportion of sheep with a loss of embryos was 24.6% (partial loss
      of embryos 18.0%, total loss of embryos 6.6%). In conclusion, transrectal
      ultrasound is a good method to describe the early pregnancy in sheep.

PMID- 8999590
TI  - [Clinical findings and pathology of congenital polycystic renal disease in the
      goat].
AB  - The clinical and pathomorphological findings of the spongy (cases 1, 2 and 3) and
      large-vacuol polycystic kidney disease in four kids are presented. The age of the
      goats ranged from one week to three months. In case 1 clinical examination
      including laboratory testing was performed, whereas in cases 2, 3 and 4 only the
      kidneys were available. Based upon the neurological examination a forebrain
      lesion was localized in case 1. Laboratory examinations revealed an azotemia and
      uremic encephalopathy was suspected. Gross pathology demonstrated bilateral
      polycystic kidneys and proliferation and ectasy of the intrahepatic choledochus
      system. Histopathology of the brain showed multiple alterations, such as malacia,
      edema, inflammation and a hemorrhagic area. As in other species, a genetical
      background of the disease is suspected because the twin of case 1 demonstrated
      similar symptoms.

PMID- 8999591
TI  - [Veterinary medical offer for udder health and milking hygiene: results in
      Rheinland-Pfalz].
AB  - A sanitation programme was installed by veterinary medical officers on 261 dairy
      farms. All farms had been selected because of problems with somatic cell counts
      in milk for a long period of time. Quarter milk samples were taken from all
      lactating cows, and management factors (including milking equipment, -hygiene,
      housing and feeding) were assessed. Contagious mastitis pathogens like Sc.
      agalactiae and Staphylococci represented the main bacteriological problem in 79%
      of the herds. Only minor problems were caused by environmental pathogens like
      esculin-positive Streptococci and Coliforms. The sanitation programmes were
      mainly based on improvements with milking hygiene and techniques. Recommendations
      for antibiotic therapy were also given. Farmers and veterinary surgeons were
      entirely responsible for the implementation of these programmes on the farm.
      Success was controlled by monitoring somatic cell counts in bulk milk four months
      before to 18 months after the veterinary medical officer visited the farm. As
      early as one month after the visit cell counts decreased significantly (p < 0.01)
      and continued decreasing during the second (p < 0.05) and following months.
      Somatic cell counts of bulk milk stabilised on a significantly lower level for
      all over the period monitored.

PMID- 8999592
TI  - [Bioavailability of cadmium: effect of vitamin C and phytase in broiler
      chickens].
AB  - Though the application of the toxic heavy metal cadmium is reduced, its
      concentration in soil and in feed still increases. Especially smoking habits and
      unbalanced diets cause cadmium intake in humans beyond the limits suggested by
      WHO. One possibility to reduce cadmium burden is to influence the bioavailability
      of cadmium in the feed by certain vitamins, trace elements and other feed
      components and thus to lower its content in food from animal origin. In the
      present study the influence of vitamin C and phytase on the bioavailability of
      cadmium was investigated in broiler chicken. It was shown that 1 g vitamin C per
      kg of feed lowered cadmium accumulation in kidney and in liver by up to 40%.
      Addition of phytase, a new feeding enzyme, licensed in 1992 in Germany for
      improving phosphate utilization from phytate, lowered cadmium accumulation by up
      to 60%. Therefore the addition of these two components to the feed lowers the
      cadmium burden in food from animal origin and thus increases its quality.

PMID- 8999593
TI  - [Endoparasites of donkeys and horses kept in communal housing in Upper Bavaria;
      species spectrum and incidence].
AB  - In this epidemiological study of endoparasites 37 donkeys and 23 horses were
      included, which were examined coproscopically in regular intervals over a 15
      month period. The animals derived from ten farms, in which regular prophylactic
      treatments with anthelmintics had been practiced at least for two years before
      this investigation. This study revealed the presence of at least twelve parasite
      species in donkeys, Eimeria leuckarti, Gasterophilus intestinalis, Fasciola
      hepatica, Anoplocephala perfoliata, Strongyloides westeri, Parascaris equorum,
      Dictyocaulus arnfieldi, Trichostrongylus axei and small strongyles, whose third
      stage larvae were characterized by eight, twelve, 16 or 18 intestinal cells. At
      least four parasite species were established in horses, E. leuckarti, G.
      intestinalis, P. equorum and small strongyles, whose third stage larvae were
      provided with eight intestinal cells. Infections with E. leuckarti, S. westeri
      and P. equorum were encountered in foals only and with D. arnfieldi in 16.2% of
      the donkeys. Incidences for small strongyles were highest, exhibiting neither age
      and farm-dependent nor host species-dependent differences and amounting to 91.9%
      in donkey and 86.6% in horses. Considering all donkeys and horses, 35.1% and
      43.5%, respectively, were infected at least with two, and 29.7% and 4.3%,
      respectively, with three parasite species. The species composition of the
      endoparasite fauna was always dominated by small strongyles. This field study
      indicates that the species composition of the endoparasite fauna in comparison to
      former investigations has not or only slightly changed in spite of widespread use
      of broad-spectrum anthelmintics for years. In addition, it has to be considered
      that donkeys continue to act as reservoir of D. arnfieldi and as source of
      infection for horses.

PMID- 8999595
TI  - [Determination of canine thyroid stimulating hormone (cTSH) in blood serum of
      dogs and its reaction to the TRH stimulation test].
AB  - The introduction of the determination of canine TSH in the blood serum of the dog
      means a substantial enrichment in the diagnosis of thyroid disease. In the
      present study the basic value of serum c-TSH and its maximal increase after
      intravenous injection of 200 micrograms TRH per dog were determined. The basic
      value was 0.18 +/- 0.11 ng/ml, the maximal increase was reached between 15 and 30
      minutes after injection of TRH and was 0.53 +/- 0.24 ng/ml. In two hypothyroidal
      dogs the basic values of T4 were 1.1 and 0.56 microgram/dl and of fT4 0.19 and
      0.15 ng/dl, respectively. Their TSH concentration was 1.35 and 4.0 ng/ml,
      respectively.

PMID- 8999594
TI  - [Strangulation ileus of the jejunum combined with intersexuality in a horse].
AB  - An apparently unilateral cryptorchid stallion was referred to the clinic with a
      history of colic. In the course of laparotomy an ileus caused by strangulation of
      the small intestine was found and the horse was euthanized because of poor
      prognosis. During autopsy strictures and ectasia of the jejunum were found as
      well as hermaphroditism along with male phenotype. The frequency of
      cryptorchidism in the case of intersexuality is discussed.

PMID- 8999596
TI  - [Total intravenous anesthesia (TIVA) with alphaxolon/alphadolon (Saffan) for
      permanent restraint of two cats with severe dyspnea].
AB  - Total intravenous anaesthesia is a form of anaesthesia which is more often used
      in human medicine for high risk patients. The case reports of two cats with a
      severe dyspnoe are presented. Both patients received anaesthesia with the steroid
      anaesthetic agent Saffan for 19 and 25 hours, respectively. Saffan is a well
      tolerated agent with little side effects. Dosage and monitoring results are
      presented.

PMID- 8999597
TI  - [A case of necrotizing meningoencephalitis in a pug dog (pug dog encephalitis-
      PDE)].
AB  - A three-year-old female pug dog was euthanized because of recurrent seizures.
      Pathological examination revealed severe multifocal necrosis confined to the
      cerebrum. Histologically, areas of malacia of different stages, with prominent
      gitter cell infiltration were observed. Furthermore, there was severe
      rarefication resulting in cavities separated by tissue bridges and blood vessels.
      In the adjacent tissue and in the meninges a moderate to severe non-purulent
      meningoencephalitis was evident. The lesions are consistent with those reported
      for pug dog encephalitis (PDE). In the present paper, the first case of PDE in
      Germany is described and an overview of the clinical symptoms, the
      neuropathological findings of this etiologically unknown disease, the
      differential diagnoses and the possible pathogenesis is given.

PMID- 8999598
TI  - [Cordylobia anthropophaga as a cause of cutaneous myiasis in a dog in Germany].
AB  - This paper reports on a case of cutaneous myiasis due to Cordylobia anthropophaga
      in a dog imported from Cameroon to Germany. An account is given of the biology
      and ecology of this skin maggot fly as well as the clinics, diagnosis and
      treatment of the cutaneous myiasis are reviewed.

PMID- 8999599
TI  - [Specific immunotherapy of canine atopy. A prospective clinical study using
      tyrosine adsorbents].
AB  - It is reported about a non-randomized prospective study of the treatment of 17
      atopic dogs over a nine-months-period using tyrosine-precipitated vaccines. All
      dogs were presented because of perennial atopic skin diseases at a practice for
      internal medicine between 1992 and 1995. The clinical degree of pruritus and
      dermatitis was controlled before, after three, six, and nine months of
      immunotherapy individually. After nine months of immunotherapy five dogs showed a
      reduction of the symptoms for more than 75%, six dogs for more than 50%, six dogs
      for less than 50%. Eleven (65%) dogs were classified as having been successfully
      treated, six (35%) showed poor clinical response. Tyrosine-precipitated vaccines
      were found to be helpful in the treatment of atopic skin diseases of the dog.

PMID- 8999600
TI  - [Bone scintigraphy and arthroscopy--diagnostic methods for the detection of
      lameness in dogs].
AB  - For the detection of lameness in the dog two additional diagnostic methods-bone
      scintigraphy and arthroscopy-are available. The cooperation of these techniques
      in the clinical diagnosis is presented by case examples. The techniques and the
      applicabilities of bone scintigraphy and arthroscopy are shown and discussed.

PMID- 8999601
TI  - [The "other" parvovirus: first description of the minute virus of canines (Canine
      parvovirus type 1) in Germany].
AB  - During an investigation of a late abortion in a Yorkshire terrier minute virus of
      canines (MVC) antigen could be demonstrated in fetal tissues by
      immunofluorescence. The bitch had a high specific anti-MVC serum titer when
      tested about four weeks after the abortion. Those results implicate an
      etiological role of MVC in this abortion and to our knowledge it presents the
      first described case of a MVC-associated abortion in Germany.

PMID- 8999602
TI  - [Is there a superantigen effect on steroid-responsive meningitis-arteritis in
      dogs?].
AB  - Steroid responsive meningitis-arthritis in the dog is a frequently occurring
      disease in small animal practice. However, the etiology and pathogenesis are
      unknown. Immunopathologic events are suspected, since IgA seems to play a central
      role in pathogenesis. The influence of an infectious agent is possible. To
      classify the nature of such an agent, we tried to find in this study an
      oligoclonal T-cell proliferation using Southern blot technique. This could give a
      hint for an infection with a superantigen. In a first step a proliferation assay
      was performed, proving that staphylococcus enterotoxins A and B induce a strong
      lymphocyte proliferation in the dog in vitro. In one out of six dogs with steroid
      responsive meningitis-arthritis T-cell receptor rearrangement was detected after
      digestion of genomic DNA with two different restriction enzymes. Therefore a
      superantigen influence in this specific disease seems to be possible, but could
      not be proven finally using Southern blot techniques.

PMID- 8999603
TI  - [Study of long-term anesthesia in rabbits].
AB  - In this study, the possibility of total intravenous anaesthesia with the
      anaesthetic agents etomidat/fentanyl, ketamine/xylazine and maintenance with
      halothane, nitrous oxide and oxygen was used in rabbits for long-term
      experimental surgery with median sternotomy. The clinical course, cardiovascular
      and respiratory parameters undergoing long-term anaesthesia for experimental
      cardiac surgery in rabbits were evaluated.

PMID- 8999604
TI  - [Plasma viscosity in the dog].
AB  - Plasma viscosity (PV) was examined in healthy (n = 122) and sick (n = 58) dogs.
      The mean value of PV in healthy adult dogs is 1.22 mPas. PV is remarkably
      increased in case of illness. In dogs with chronic heart failure the mean value
      was 1.46 mPas. Patients suffering from uraemia or pyometra revealed mean values
      of 1.90 mPas and 1.96 mPas respectively. An elevation of the PV is correlated
      with an increase of the "acute-phase-proteins". The examination of PV is useful
      for a better assessment of microcirculation. The PV is a parameter, which is
      important in diagnostics as well as in follow-up during special therapeutical
      procedures.

PMID- 8999605
TI  - Effect of anti CD45 on different immunosuppressive regimes in renal
      transplantation.

PMID- 8999606
TI  - Transplantation of kidneys with vascular anomalies or harvesting injury into
      pediatric recipients.

PMID- 8999607
TI  - [Just a hernia--one more time?].

PMID- 8999608
TI  - [Sick leave for pregnant women].

PMID- 8999609
TI  - [A vaccine against HIV--status after ten years of research].

PMID- 8999610
TI  - [Neuroendocrine disorders in anorexia nervosa--primary or secondary?].
AB  - Anorexia nervosa is associated with multiple endocrine abnormalities.
      Hypothalamic neuropeptides and monoamines are involved in the regulation of human
      appetite, and they are changed in several ways in anorexia nervosa. But it
      remains to be clarified whether these alterations are secondary or etiologic.
      Feeding behaviour in anorexia nervosa is characterised by a strong ambivalence
      and not by loss of appetite. Hypothalamic amenorrhea is a diagnostic criterion,
      and is not only secondary as it often precedes the weight loss and persists for a
      long time after weight and motor activity have returned to normal. Hypersecretion
      of corticotropin releasing hormone seems to be secondary to starvation, but at
      the same time it may keep up and intensify the anorexia, physical hyperactivity
      and amenorrhea. Low production of insulinlike growth factor-I and high growth
      hormone secretion reflects the nutritional deprivation. In conclusion most of the
      neuroendocrine abnormalities are secondary to weight loss, but some of them seem
      to participate in a circulus vitiosus and maintain the emaciated state.

PMID- 8999611
TI  - [Recurrence of inguinal hernia: ambulatory surgery under local anesthesia].
AB  - In order to assess the feasibility of repair of a recurrent inguinal hernia in
      unmonitored local anaesthesia in an ambulatory set-up pain scores and data on
      patient satisfaction were obtained from 76 unselected patients after 79
      consecutive operations. Median age was 63 years, and 25%- and 75% quartiles were
      49 and 72 years respectively. All operations were conducted in local anesthesia.
      Three patients stayed in hospital overnight after the operation. Pain: After one,
      six and 28 days 27, 14 og 7% respectively had severe pain during function (cough
      and/or rising). Satisfaction: 82% were satisfied with ambulatory surgery in local
      anaesthesia, 82% were satisfied with the analgesic therapy (tenoxicam and
      methadone), but one third needed supplementary analgesics during the first week
      (acetaminophen was recommended). It is concluded, that ambulatory repair of a
      recurrent inguinal hernia in unmonitored local anaesthesia is a safe and cost
      effective alternative to operation in general or spinal anaesthesia.

PMID- 8999612
TI  - [Tension-free inguinal and femoral hernioplasty using a mesh of plastic
      material].
AB  - This study represents 202 consecutive cases of inguinal- or femoral hernias
      treated at the Department of Surgery, Silkeborg Central Hospital, Denmark. All
      were operated with the tension-free mesh-plug technique as described by Rutkow &
      Robbins (4). The median duration of the operation for the primary hernias was 35
      (30-45) minutes, (median(25-75 percentile)), and 45 (30-60) minutes for the
      recurrent hernias. The operation was performed as a day-in procedure in 62% of
      the patients, whereas 35% stayed in the ward overnight. All daily activities,
      including strenuous exercises, were resumed within seven (2-14) days. Seven
      patients developed haematomas, none of which required treatment. One case of
      superficial infection required opening of the wound. Three recurrences have been
      reoperated, all using the mesh-plug technique and all with good results, while
      another three recurrences are suspected in patients with no or few complaints. It
      is concluded that inguinal- and femoral mesh-plug hernioplasty is a safe,
      efficient and low-cost procedure.

PMID- 8999613
TI  - [Pregnancy and occupational environment. Counseling of pregnant women in the
      department of occupational medicine during the period 4 January--31 December
      1992].
AB  - Since the new Sickness and Maternity Benefit Act was introduced in Denmark 1981,
      it has been possible to provide maintenance allowance for pregnant women working
      under conditions that might be harmful to the unborn child. The assessment of the
      risk is primarily undertaken by the general practitioner, but in cases of doubt,
      the pregnant women can be referred to the Department of Occupational Medicine.
      The assessment at the Department of Occupational Medicine is made one or two
      weeks after referral. It consists of a careful work history, which includes
      characterization of exposure, both qualitatively and quantitatively and a
      decision whether the exposure entails a risk to the foetus and which steps should
      be taken for the rest of the pregnancy. The purpose of this study was to describe
      the practice of risk assessment at the Department of Occupational Medicine in
      Denmark. Over a period of nine months all cases of pregnant women referred to 12
      out of 14 departments were reviewed. Out of 60,000 births per year only 250
      pregnant women were referred, which is less than 1%. Main risk factors in the
      assessment were of chemical (80%) or ergonomic (17%) origin. Forty-three percent
      were advised to leave work on maintenance allowance and 15% were advised to stay
      at work, on condition that the work environment was changed or they could be
      moved to a job without risk exposure. The study revealed big differences in
      referral incidence between the different counties as well as differences in risk
      assessment practice. It is concluded, that the best way to secure pregnant women
      and their foetus is by primary prophylactic measures at the workplace. Hopefully
      the new EU Directive 92/85 will be a step in that direction.

PMID- 8999614
TI  - [Sick leave for pregnant women in the municipality of Fjend 1987-1990].
AB  - All of 417 pregnancies in 1987-1990 in a rural community were retrospectively
      evaluated with emphasis on age, parity, previous spontaneous or induced abortion,
      occupation during pregnancy and sick leave from work. No difference was found in
      prevalence of sick leave between the employed women and the unemployed. Thirty
      five percent of the women experienced sick leave at some time during pregnancy.
      The greatest single diagnostic group was pelvic insufficiency, which accounted
      for 33.5% of all days of sick leave up to the 32nd week of gestation. The
      incidence of pelvic insufficiency was high: 76 in 1000 deliveries. This may in
      part be due to a change in diagnostic criteria. Logistic regression analysis
      revealed that being a multipara was associated with a significantly higher risk
      of sick leave in the present pregnancy. Furthermore, being employed as a nurse, a
      shop assistant, a seamstress or a factory worker was associated with a
      significantly higher risk of sick leave during pregnancy in comparison with
      employment as a secretary. When investigating relationships between occupational
      conditions and the outcome of pregnancy, sick leave during pregnancy because of
      the same conditions may interfere significantly.

PMID- 8999615
TI  - ["Linguistitis" of medical terminology (I)].
AB  - A 1994/95 survey on language and terminology in emergency wards revealed a number
      of contradictory tendencies within today's Danish medical terminology. On the one
      hand, an increasing number of medical terms are nationalized. This tendency is
      reflected not only in intercollegial language, but also in the Danish version of
      the ICD-10 where a number of official diagnostic terms are casually translated
      into Danish or undergo various degrees of nationalization to appear as hybrids.
      On the other hand, knowledge of English becomes increasingly important: good
      passive command of the language is a must for medical students, and doctors
      committed to research need a good active command as well. This situation raises a
      number of questions: is there a need for setting up criteria for the terminology
      used in Danish medical literature and encyclopedia in order to avoid confusion,
      and for defining a language policy for future medical doctors?

PMID- 8999616
TI  - ["Linguistitis" of medical terminology (II). Language-policy and questions from a
      perspective of younger physicians].
AB  - In a previous article in the Journal of the Danish Medical Association, "Medical
      Terminology Linguistitis (I)", the author pointed out the importance of involving
      the users in connection with the definition of a language policy concerning
      Danish medical terminology and future medical doctors' need for language
      proficiency. A recent inquiry, involving 11 medical doctors (Ph.D. students),
      suggests that there is in fact a need for a language policy. Also, the
      respondents expressed strong antipathy against a full nationalization of the
      terms which can in some cases be observed in the Danish version of ICD-10. On the
      basis of this survey, the following questions are discussed in this article:
      Future medical doctors' need for knowledge of Latin and English, medical doctors'
      opinions concerning a terminology based on Latin, or Danish, and some important
      aspects concerning the definition of a language policy in the medical area.

PMID- 8999617
TI  - [Round-the-clock blood pressure measurements in 352 persons--a reference
      material].
AB  - The aim of this study was to establish reference values for 24-hour ambulatory
      blood pressure in a Danish population stratified for gender and age in the
      decades from 20 to 79 years of age. A sample of 352 persons, 179 men and 173
      women randomly selected from the local community register, age 20-79 years
      underwent 24-h ambulatory blood pressure monitoring. For men age < 50 daytime
      ambulatory blood pressure (median) was 125/79 mmHg and night time was 106/65
      mmHg, for women the respective pressures were 113/77 mmHg and 97/64 mmHg. For men
      age > or = 50 daytime ambulatory blood pressure was 133/83 mmHg and night time
      was 124/86 mmHg, for women the respective pressures were 122/83 mmHg and 105/65
      mmHg. Presently, we can only relate cardiovascular risk to clinic blood pressure.
      Therefore we have calculated corresponding ambulatory blood pressure values to
      WHO's upper limit 160/90 mmHg for normal blood pressure in the clinic and found
      154/87 mmHg for daytime and 134/74 mmHg at night. For a clinic pressure of 95
      mmHg the corresponding daytime value was 91 mmHg, for 100 mmHg it was 95 mmHg.

PMID- 8999619
TI  - [Deep subacute accidental hypothermia. A case with an unusual clinical picture
      and course].
AB  - A case of a patient with core temperature of 24.4 degrees C, presenting an
      unusual clinical picture, is described. A 68 year-old man was found outdoors
      after being exposed to five to eight hours of coldness. He was found awake, with
      dry clothes and an alcohol foetor. After eight hours the serum ethanol was
      measured as 6 mmol/l. He could not speak but was able to move all four
      extremities. A sinus bradycardia of 23 beats per minute was present but no other
      arrhythmia was seen. The temperature rose to 31.2 degrees C within four hours and
      body temperature was normal after 10 hours. The only treatment given was passive
      rewarming with blankets and 2.5 l isotonic NaCl warmed to 40 degrees C given
      intravenously. This clinical picture supports the assumption that ethanol
      protects the myocardium against arrhythmias in deep hypothermia.

PMID- 8999618
TI  - [Formoterol as inhalation powder in the treatment of patients with reversible
      obstructive lung diseases. A 3-month placebo-controlled comparison of the effects
      of formoterol and salbutamol, followed by a 12-month period with formoterol
      alone].
AB  - This article is based on a study first published in Allergy. The bronchodilating
      effect of the long acting beta 2-agonist formoterol dey powder (dp) 12 micrograms
      twice daily was compared to salbutamol 400 micrograms four times daily and
      placebo in patients with reversible obstructive airway disease. The study design
      consisted of a closed 12-week double-blind, placebo-controlled, multicentre trial
      followed by an open noncomparative, multicentre 12-month follow-up trial, in
      which tolerability of formoterol dp was assessed. A total of 304 patients aged 18
      79 years were randomized. The bronchodilating effect of formoterol, assessed by
      morning premedication peak flow rate, was significantly superior to placebo (p <
      0.0001) and salbutamol (p < 0.001). Efficacy was maintained during the open
      follow-up study. Formoterol 12 micrograms twice daily significantly reduced
      morning and evening asthma symptoms and sleep disturbances, and significantly
      reduced the need for rescue medication. In conclusion, formoterol 12 micrograms
      dp twice daily was significantly superior to both salbutamol 400 micrograms dp
      four times daily and placebo, and reduced asthma symptoms significantly. Overall,
      formoterol showed a tolerability profile comparable to that of salbutamol, and no
      tachyphylaxis was observed during one year of treatment.

PMID- 8999620
TI  - [Radiologic assessment of the effect of chemotherapy in malignant bone
      neoplasms].

PMID- 8999621
TI  - [Molecular biology diagnosis and monitoring in acute lymphoblastic leukemia and
      non-Hodgkin-lymphoma].

PMID- 8999622
TI  - [Diagnostic imaging in low back pain and prolapsed disk].

PMID- 8999624
TI  - [Pre-anesthesiologic preparation for urologic operations. I: Screening for
      anesthesia].

PMID- 8999623
TI  - [Management and surgical treatment of prolapsed disk and spinal stenosis].

PMID- 8999625
TI  - [Basic research in uro-oncology--molecular biology emphasis and gene transfer
      techniques].

PMID- 8999628
TI  - [Basic principles of gene therapy].
AB  - The rapid development of recombinant DNA technology and our enhanced
      understanding of the genetic basis of human disease has facilitated the
      development of new molecular therapeutic modalities, termed gene therapy. Gene
      therapy involves the transfer of functional genes into somatic cells and their
      expression in target tissues in order to replace absent genes, correct defective
      genes, or induce antitumoral activity in the tumor-bearing host. Currently, an
      increasing number of gene therapy strategies are being investigated in
      experimental and clinical trials. Despite substantial progress, a number of
      technical and logistical hurdles must still be overcome before gene therapy can
      be safety and effectively applied in the human patient. Since gene therapy
      involves complex cell processing and can be time consuming and costly,
      simplifications or even alternative approaches will be necessary in order to
      establish this therapy as suitable for clinical use. This report reviews various
      gene therapy strategies and gene delivery techniques currently under clinical or
      experimental investigation. Special emphasis is given to cytokine gene therapy
      using gene-modified tumor vaccines for cancer treatment.

PMID- 8999626
TI  - [Angiogenesis--principles and significance in urologic tumors].
AB  - Physiologically, angiogenesis in adults is a controlled process which plays a
      role, for example, in wound healing. Pathological angiogenesis is observed in
      tumor formation and represents a multifactorial process, in which specific
      angiogenic factors, as well as growth factors, extracellular matrix proteins and
      cell adhesion molecules are involved. Tumor growth is characterized by an
      imbalance in favor of angiogenic over angiogenesis-inhibiting factors. Some of
      the most frequently examined angiogenic factors are vascular endothelial growth
      factor, acidic/basic fibroblast growth factors and the platelet-derived
      endothelial cell growth factor. The most important angiogenesis inhibitors are
      angiostatin and thrombospondin. To date, the clinical relevance of tumor
      angiogenesis has been shown for several human tumors. For most urological tumors,
      the grade of tumor vessel formation, measured as microvessel density, has been
      associated with metastases, tumor growth and clinical course. The prognostic
      value of this feature of malignant growth seems to be higher than that of most of
      the classical and newer prognostic factors. Systematic investigations of tumor
      angiogenesis are becoming increasingly relevant for diagnostic and therapeutic
      strategies and offer opportunities for the development of new specific
      therapeutic approaches in clinical oncology.

PMID- 8999627
TI  - [Adhesion molecules in urologic tumors].
AB  - Adhesion molecules play an important role in organogenesis, would healing,
      inflammation, and progression of malignant tumors. Three major classes of
      adhesion molecules may be discriminated by function: (a) calcium-dependent
      homotypic adhesion molecules (e.g. cadherins), (b) substrate adhesion molecules
      (e.g. integrins) and (c) heterotypic adhesion molecules (e.g. ICAM-1). Molecules
      of each of the three classes have been identified in urologic tumors. Results of
      research on substrate adhesion molecules and heterotypic adhesion molecules have
      not yet led to new clinical concepts. In contrast, loss of E-cadherin in tumors
      of the bladder and prostate has been clearly associated with de-differentiation
      of tumors and diminished survival of patients. Loss of another adhesion molecule,
      C-CAM, has been observed in prostate cancer. This has led to new therapeutic
      approaches, which are in an experimental stage at present. It may be expected
      that, in the future, new therapeutic concepts will be based on research on
      adhesion molecules in urologic tumors.

PMID- 8999629
TI  - [Apoptosis--principles and importance of programmed cell death for prostatic
      carcinoma].
AB  - Apoptosis, or programmed cell death, plays an essential role in specific cell
      deletion during normal embryonal and adult development. Apoptotic cells are
      characterized by fragmentation of nuclear DNA and formation of apoptotic bodies.
      Molecular genetic analysis has revealed the involvement of several deaths and
      survival genes that are regulated by extracellular and intracellular factors.
      There are multiple inducers and inhibitors which interact with target
      cellspecific receptors and transduce signals involved in cellular proliferation,
      cell cycle progression and programmed cell death. The elimination of tumor cell
      populations by applying lethal doses of chemotherapeutic agents or radiation is a
      well-established strategy in cancer therapy. Although improved cytotoxic chemo-
      and radiotherapy regimens are available, the efficacy of these strategies is
      still disappointing with regard to many solid tumors. Better understanding of the
      molecular mechanism of apoptosis, including death genes, death signals, receptors
      and signal transduction pathways, will provide new approaches in the development
      of strategies to regulate malignant cell survival and death. Recent discoveries
      in the field of apoptotic cell death promise to have a significant impact on
      antitumor therapies. Apoptosis is known to be an active process which can be
      artificially manipulated by several molecular pathways. This information
      concerning the regulation and induction of programmed cell death might lead among
      other things, to the development of new powerful means to eliminate malignant
      cell populations of otherwise resistant genitourinary tumors such as prostate
      cancer.

PMID- 8999630
TI  - [Significance of prostate-specific membrane antigen (PSMA). A
      neurocarboxypeptidase and membrane folate hydrolase].
AB  - Prostate specific membrane antigen (PSMA) is a novel prostate marker that is
      highly expressed in normal prostate as well as in prostate cancer. Its expression
      is increased in prostate cancer and is found primarily in the prostate. PSMA is
      considered to be a type II membrane protein with a 54% homology to the
      transferrin receptor. However, in normal prostate, PSM', an alternatively spliced
      form of PSMA, is localized in the cytoplasm. The PSMA functions as both a
      neurocarboxypeptidase and folate hydrolase and may therefore be involved in the
      neuroendocrine regulation of prostate growth and differentiation. The implication
      of these findings is currently under investigation. In this article the cloning
      of the PSMA gene, its possible role as a therapeutic target and its implication
      as a diagnostic tool with regard to the molecular staging of prostate cancer is
      reviewed.

PMID- 8999631
TI  - [Studies of calcium metabolism in patients with hypercalciuria].
AB  - The different subgroups of hypercalciuria cannot be separated clearly by the Pak
      calcium-load test. To improve the diagnosis and therapy we examined all relevant
      parameters of calcium metabolism in 32 patients with calcium urolithiasis and
      hypercalciuria (> 6.25 mmol/day). We also conducted bone mineral density
      measurements as well as the Pak calcium-load test. In most cases the
      pathophysiological constellations which Pak takes as the basis for his
      classification of hypercalciuria could not be shown. To date, diagnostics only
      insufficiently explains the genesis of hypercalciuria (except pHPT). As a
      consequence, a therapeutic problem arises: a low-calcium diet should not be
      generally recommended, since some patients may develop osteopenia. From our
      investigation the following diagnostic and therapeutic conclusions can be drawn:
      (1) Hypercalciuria in primary hyperparathyroidism should be treated by surgical
      removal of the adenoma. (2) The parathormone-independent osteogenic form should
      be treated with thiazides. (3) Hypercalciuria with increased 1.25
      dihydroxyvitamin D should be treated by low-calcium diet.

PMID- 8999632
TI  - [Laparoscopic lymphadenectomy in prostate carcinoma. Experiences with 120
      patients].
AB  - Laparoscopic pelvic lymph node dissection was performed in 120 patients scheduled
      to undergo either radical perineal prostatectomy or radiation therapy. On average
      13 lymph nodes were resected in each patient, and 21 patients were found to have
      metastatic disease in 1-9 lymph nodes. After an initial learning curve, mean
      operative time was reduced significantly, allowing laparoscopic lymph node
      dissection and radical prostatectomy to be performed as a one-stage procedure.
      The overall complication rate was 10%; open revisions were necessary in only 2 of
      120 patients. Postoperative hospital stay was 2 days in patients undergoing
      laparoscopic lymph node dissection only. This minimally invasive procedure is
      particularly beneficial to patients with lymph node metastases not undergoing
      radical prostatectomy, as well as to patients planned to be treated by radiation
      therapy. The combination of laparoscopic lymph node dissection and radical
      perineal prostatectomy avoids an abdominal incision and thus shortens both the
      hospital stay and the period of convalescence.

PMID- 8999634
TI  - [International Symposium on Penile Diseases. Hamburg, 26-27 January 1996].

PMID- 8999633
TI  - [Symptomatic congenital arteriovenous malformation in the man].
AB  - A congenital arteriovenous malformation in the pelvic cavity is extremely rare
      and most patients have vague and longstanding pelvic symptoms before an exact
      diagnosis is made. We treated a 50-year-old man who suffered from recurrent
      pelvic pain. The diagnosis was confirmed by rectal palpation, colour Doppler
      ultrasonography, computed tomography and arteriography. The patient was treated
      successfully by ligation of the nutrient vessels to reduce the perfusion volume
      by thrombosis of the malformation. Complete resection of the arteriovenous
      fistula, which involves a high risk of extensive blood loss, was not necessary.
      Three years after surgical intervention the patient has no complaints and no
      rectal pulsation.

PMID- 8999635
TI  - [Malformations of intranasal structures and rhinosinusitis in children].
AB  - 240 patients with acute and 233 children with chronic nasal and paranasal sinus
      disease aged under 14 years have undergone endoscopic examination. It was found
      that the number of serious developmental defects hindering drainage of the
      paranasal sinusis was higher in children with rhinogenic orbital complications
      than in those with acute sinusitis. Chronic affections of the nose and paranasal
      sinusis in most examinees were accompanied by malformations of the intranasal
      structures deteriorating mucociliary transport both in nasal cavity and paranasal
      sinusis. The occurrence of the above and septal defects increased with age. The
      conclusion is made that defects of the intranasal structures contribute
      significantly to the onset of acute sinusis (AS) in children, AS transformation
      into chronic form, emergence of complications along with general and local
      immunodeficiency, microbial virulence. The findings support the principal
      conception of sinusitis pathogenesis offered by W. Messerklinger which justifies
      early functional endoscopic operations in nasal cavity for prevention and
      treatment of nasal and paranasal diseases.

PMID- 8999636
TI  - [Variants and early symptoms of congenital diseases of larynx and trachea].
AB  - Congenital laryngeal and tracheal anomalies found in 1980-1995 in 91 children
      consisted of vascular tumors, laryngeal membranes, laryngeal cartilage anomaly,
      tracheomalacia, laryngeal papillomatosis, cysts, stridor (36.2%, 16.5%, 13.2%,
      3.3%, 13.2%, 5.5%, 9.9%, respectively). Other causes are responsible for the
      defects in 2.2% of cases. Early symptoms of the above diseases are detailed. This
      information contributes to valid preliminary diagnosis and to optimal planning of
      further examination and treatment.

PMID- 8999637
TI  - [Dysphagia in infants].
AB  - 39 cases of congenital dysphagia in infants treated by the author provided
      evidence for advantage of rigid and fibrooptic endoscopy in examination of such
      patients. High informative value in detection of swallowing defects is attributed
      to high-speed cinorhoentgenography with low-speed film review. Recommendations on
      the treatment of infantile traumatic dysphagia are given. The insertion of small
      size permanent thermoplastic esophageal tube for the period of dysphagia
      treatment is advisable.

PMID- 8999638
TI  - [Preoperative and postoperative management of patients with congenital defects of
      the external and middle ear].
AB  - Laser techniques introduction in preoperative and postoperative management of
      patients operated for congenital defects of the external and middle ear promotes
      retention of the graft and activation of regeneration, improves treatment
      results. More advanced methods of care for the postoperative cavity increase
      quality and duration of hearing-improving operative effects, shorten hospital
      stay, minimize risk of long-term complications.

PMID- 8999639
TI  - [Reconstruction of the floor of the auricle in congenital microtia in children].
AB  - The data are presented on 329 children (201 boys and 128 girls) with congenital
      defects of the external and middle ear. Right-side defect occurred twice as
      frequently as left-side one. Treatment in 45 children with bilateral defects
      started with reconstructive meatotympanoplasty. Surgical reconstruction has been
      performed on 106 floors of the auricle. In 51 cases a rib homocartilage and free
      skin were used (group 1), in 55 cases alloplastic frames were covered with
      pedicle tissue (group 2). The following complications occurred in group 1: a
      complete resorption of the cartilage, necrosis of the skin graft, decubitus (5, 5
      and 6 cases, respectively). In group 2 there were 5 cases of the pedicle
      necrosis, 7 cases of the pedicle self-detachment, 7 cases of the frame
      sequestration, 2 cases of late frame displacement. The floors formed with the use
      of neck-chest pedicle and compound silicone frame produced the best cosmetic
      effects.

PMID- 8999640
TI  - [Congenital cysts and fistulas in the central neck of children].
AB  - Surgical treatment for central neck congenital cysts and fistulas including 19
      recurrences has been performed in 85 children aged from 9 months to 15 years. The
      recurrence after 91 operations was recorded in 6 patients (6.1%). The authors
      advocate surgical intervention at any age early after the diagnosis.

PMID- 8999641
TI  - [Congenital periauricular fistulas in children: diagnostic difficulties].
AB  - Such congenital defects as periauricular fistulas are not rare in children. In
      typical position of the fistulas on the tragus the diagnosis is easy. In
      involvement of the floor, lobule and margin of the auricle, acoustic meatus the
      treatment, because of misdiagnosis, is often given for atheroma, lymphadenitis,
      tumors, eczema, etc. Valuable information for early accurate diagnosis may be
      obtained from detailed analysis of the disease history, thorough examination of
      the parotid region. Fistulas are treated surgically in the exacerbation-free
      period after fistulography.

PMID- 8999642
TI  - [Congenital choanal atresia].
AB  - In 1990-1995 the authors treated 40 children (age 1 month to 12 years) with
      congenital choanal atresia (CA). Bilateral CA occurred in 4, unilateral in 36
      children. Complete and incomplete CA were diagnosed in 37 and 3 patients,
      respectively. Other congenital anomalies were registered in 7 children.
      Fibroendoscopy and computed tomography proved best in providing diagnostic
      information, while endonasal method with finger control was most available. The
      optimal time of protector carrying was at least 2.5 months.

PMID- 8999643
TI  - [The effect of perinatal factors on development of congenital sensorineural
      hearing loss in children].
AB  - Combined treatment with hyperbaric oxygenation (HBO), antihypoxants, correctors
      of microcirculatory, liquor-dynamic and metabolic disorders in the internal ear
      was used in 99 children aged 1 month to 2.5 years with perinatal neurosensory
      hypoacusis. A 10-15 dB decrease in auditory thresholds was achieved in 10% of the
      patients. HBO application in combined treatment of the above patients was
      pathogenetically validated.

PMID- 8999644
TI  - [Congenital subfold hemangioma in combination with hemangiomatosis of the head,
      face and neck].
AB  - The treatment was made of 15 children aged 3-6 months with advanced
      hemangiomatosis of the head, face, neck and larynx. The treatment combined
      hormone therapy, sclerotherapy of the tumor, staged cryodestruction of the
      external and endolaryngeal nodes. In one case the arterial occlusion was
      performed. Good cosmetic results and recovery of adequate respiration were
      achieved in 13 children.

PMID- 8999646
TI  - [A rare nasal congenital defect in a child].

PMID- 8999645
TI  - [Dystopia and laryngeal malformation in a child with Treacher Collins and Pierre
      Robin syndromes].

PMID- 8999647
TI  - [A congenital cyst of the neck complicated by hyoid bone osteomyelitis in 4-year
      old girl].

PMID- 8999648
TI  - [Dependence of immunological reactivity on blood groups and microflora in
      patients with chronic purulent otitis media].
AB  - Immunological investigation (1-2 level tests with monoclonal antibodies) of 246
      OMPC patients has discovered a relationship between the degree of immunological
      disorder, blood group and microflora. Patients carrying AII and ABIV, Pseudomonas
      aeruginosa, Staphylococcus aureus, Proteus were more immunologically compromised.
      These findings may help in the choice of profile immunocorrector.

PMID- 8999649
TI  - [Surgical treatment of congenital defects of the external and middle ear in
      children].
AB  - Incidence of congenital defects of the external and middle ear in children is 1
      2/10000. Surgical correction includes meatotympanoplasty followed by otoplasty.
      Surgical technique proposed by the authors provides persistant and satisfactory
      functional and cosmetic results.

PMID- 8999650
TI  - [Phlegmons of the neck].

PMID- 8999651
TI  - [Prevention and treatment of suppuration caused by neck trauma].
AB  - 93 cases of cervical injury are described. 39 patients developed pyonecrotic
      complications in the course of treatment. These were caused by both increased
      virulence of the microorganisms and low immunoresistance of the patients. In
      abscesses and pus absence the inflammatory infiltrate was opened and drained.
      Powder antiseptic iodopor, antibiotic epocillin, tampon ambikor, etc. were used
      postoperatively. Bacteriologically, the response was substantial.

PMID- 8999652
TI  - [Metachronous multifocal cancer of the larynx and esophagus].

PMID- 8999653
TI  - [Inhibiting effects of mixtures of alpha-tocopherol with beta-carotene or vitamin
      A during oxidation of polyunsaturated fatty acid esters].
AB  - The inhibitory activities of individual natural antioxdants (AOs), such as alpha
      tocopherol (I), beta-carotene (II), vitamin A(III) and their mixtures were
      comparatively studied when oxidation of microbial polyunsaturated fatty acid
      esters that predominately contain ethyl arachidonate was initiated; effects of
      antagonism were found in the combined action of I and II, I and III. The
      magnitude of antagonism effect was estimated from the difference between the
      total additive effects of individual AOs and the experimentally determined
      effects of their mixture. There is a U-dependence of changes in the antagonism
      values upon II concentrations at steady-state I levels. It was found that in the
      range of low (10(-8) to 10(-7) M) and high (10(-2) M) concentrations of II, the
      involvement of antagonism might be relatively low (3.5-4.0%); in the range of 10(
      6) to 10(-5) M, there is a concentration "hole" whose peak (1.25 x 10(-6) M) is
      as high as 90%. As I levels elevated, antagonism in the mixture decreased. It is
      suggested that the intermolecular interactions of natural AO during oxidation
      represent a mechanism for the body's antioxidative homeostasis.

PMID- 8999654
TI  - [Lipoprotein lipase: properties, change in activity with age and in some
      noninfectious human diseases].

PMID- 8999655
TI  - [Correction of disruption of oxidative processes by dimethyl sulfoxide and alpha
      tocopherol in acute chemical injury to the liver].

PMID- 8999656
TI  - [Effect of captopril on angiotensin-converting enzyme activity and animal
      behavior in the "open field" test].
AB  - Captopril was investigated for its effects on the activity of angiotensin
      converting enzyme in the rat blood serum, pituitary, hypothalamus, and striatum,
      as well as for those on the animals, behavior in the open-field test. During its
      single administration the agent was found to lower the activity of angiotensin
      converting enzyme in all the examined brain regions and serum. During chronic
      administration captopril decreased the mobility of the animals in the open-field
      test, diminished, the activity of the enzyme in the hypothalamus and striatum and
      enhanced it in the pituitary and serum. It is suggested that the effect of
      captopril might be due to imbalance in the changes of angiotensin-converting
      enzyme activity in various brain regions of the rats.

PMID- 8999657
TI  - [Immunoenzyme assay of staphylococcal toxin using polyamide micropore membranes].
AB  - The optimum conditions for extraction of catalytic active conjugates of alpha
      amylase and antibodies for staphylococcal toxin (ST) have been created. The
      optimum correlation of antibodies and enzyme for the effective use of the
      extracted conjugate during enzyme immunoassay for ST has been established. The
      covalent immobilization of antibodies on the micropore polyamide membranes has
      been carried out. Apart from this, the extracted conjugated were purified by TSK
      gel HN-55 chromatography. The optimum concentration of the conjugates has been
      defined.

PMID- 8999659
TI  - [Fatty acid composition of placental membrane phospholipids in women with a
      history of hypofunctional ovaries].
AB  - The fatty acid composition of plasma membranes in the placenta of induced
      pregnancy females with ovarian hypofunction was studied Palmitic, stearic, and
      oleic acids were prevalent in the placental membranes. The content of arachidonic
      acid was higher that of linoleic acid which was in greater qualities in the
      membranous lipids of other tissues than arachidonic acid. The changes found in
      the fatty acid composition of placental membranous phospholipids were associated
      with the deviations in the levels of this organ-specific hormones progesterone
      and placental lactogen.

PMID- 8999658
TI  - [Diagnostic value of studying salivary enzymes in leukemia patients].
AB  - The study was undertaken to examine the activity of the most informative enzymes
      alkaline and acid phosphatases and a-amylase in the oral fluid in patients with
      acute and chronic leukemias on admission to hospital and after oral sanitation.
      The findings of 128 patients aged 13 to 84 years who had various leukemias were
      analyzed. The control group (n = 48) included patients aged 18 to 39 years who
      had no underlying abnormality. Analysis indicated that specific changes found in
      the activities of alkaline and acid phosphatases and a-amylase in the mixed
      saliva of patients with leukemias were directly related both to the sanitation of
      foci in chronic apical periodontitis and in the oral cavity and to combined drug
      therapy.

PMID- 8999660
TI  - [Effect of actual diet on fatty acid composition of blood serum and indicators of
      immunity in Siberian and Chukotka populations].
AB  - The spectra of blood fatty acids, the true diet and the immune system were
      explored in 40-54-aged male populations of Siberia and Chukotka. There were
      differences in the serum levels of omega 3, and omega 6-polyunsaturated fatty
      acids (PUFA) in the residents od the areas under study. The blood concentration
      of omega 3-PUFA was significantly higher in the Chukchi than that in Novosibirsk
      residents, which is associated with the fact the Chuchotka inhabitants consume
      sea fish and products, which are rich in eicosapentaenoic and docosahexaenic
      acids. Excess omega 3-PUFA was found to produce an immunosuppressive effect in
      the body: in the subjects having high serum omega 3-PUFA concentrations there was
      a reduced count of T lymphocyte, killer cells, responsible for cell-mediated
      immunity, as compared to those having low omega 3-PUFA concentrations.

PMID- 8999661
TI  - [Effect of docanol on the status of hemostasis and fibrinolysis systems, as well
      as lipid spectrum in patients with ischemic heart disease depending on the
      initial level of fibrinolytic activity].
AB  - Forty patients with coronary heart disease (CHD) concurrent with hyperlipidemia
      were divided into 2 groups according to the baseline fibrinolytic activity. The
      group with the depressed fibrinolytic system displayed the highest atherogenicity
      index and levels of cholesterol, low and very low density lipoprotein cholesterol
      and half levels of high density lipoproteins. After 45-day ingestion of docanol,
      a new Russian food additive containing docosahexanoic and eicosapentaenoic acids
      there were positive changes in the lipid spectrum in the both groups. The
      fibrinolytic changes were heterodirectional: activator and plasma activities
      increased in the group of fibrinolytic depression while in the group of baseline
      normal fibrinolysis the activity of plasminogen activator fell.

PMID- 8999662
TI  - [Urinary enzymes in insulin-dependent diabetes mellitus].
AB  - In patients suffering from insulin-dependent diabetes mellitus (IDDM) with or
      without preclinical and clinical signs of diabetic nephropathy, the degree of
      epithelial cell lesions in the renal tubules was assessed from the urinary
      activities of enzymes at various sites, such as lysosomal (N-acetyl-beta-D
      glucosaminidase (NAG) and beta-galactosidase (beta-GA)), brush edge membranous
      (alanine aminopeptidase (AAP), and cytosolic (alpha-glucosidase (alpha-GL)).
      Patients from Groups 1 and 2 had no preclinical and clinical signs of
      nephropathy. In Group 1 patients, the magnitude of enzymuria was not different
      from that in normalcy. However, Group 2 patients exhibited significant increases
      in urinary NAG and beta-GA activities as compared to Group 1 patients and healthy
      individuals. In Group 3 patients with microproteinuria from 0.05 to 0.5 mg
      protein per ml urine, displayed a further enhancement of NAG and beta-GA
      activities as compared to Group 2 patients and significantly higher activity than
      did Groups 1 and 2 patients and healthy individuals. In Group 4 patients with
      macroproteinuria of > 0.5 mg/ml), greater increases in the activities of NAG,
      beta-GA, and AAP were not found, however, there was a significant increase in
      alpha-G1 activity. The findings suggest the varying degrees of epithelial cell
      damage in the renal tubules in patients of different groups and the possibility
      of early detection of lesion in the proximal portion of nephronic tubules in IDDM
      patients as assessed from urinary enzyme levels.

PMID- 8999663
TI  - [Aromatase activity in human muscle tissue].
AB  - Activity of aromatase (estrogen synthetase) was investigated in muscle tissue of
      14 women and 2 men. The method of hard water release from androgenic precursor 3H
      beta-androstendione was used. In men aromatase activity in muscle tissue is lower
      than women. For the latter group the enzyme activity is highest after 5-10 year
      of menopause and in the case of increased body fat content. In the future it
      looks interesting to correlate muscle tissue aromatase activity level with blood
      estrogens concentration, prevailing type of muscle fibers and physical activity
      rate of probands.

PMID- 8999664
TI  - [Erythrocyte metabolism in meningococcal infection and purulent meningitis].
AB  - The red blood cell metabolic parameters ATP, ADP, sigma AN, ATP/ADP, ATP/ATP,
      energy charge, PAD, 2,3-DPH, Pn were studied in 106 patients with generalized
      meningococcus infection (GMI) and meningitis of other etiology over their natural
      history. There was a typical adaptative red blood cell response that featured
      glycolytic stimulation on hypoxia that ran with impaired red blood cell energy
      metabolism (RBCEM), negative energy balance. It was the most pronounced at the
      peak of disease. RBCEM changes occurred in the presence of antioxidative
      disorders of red blood cells as lowered PAD levels. When early complications,
      such as shock, brain edema, death developed, there was a high incidence of signs
      of erythrocytic biochemical disadaptation. The RBCEM changes were associated with
      the magnitude of cytolysis, i.e. serum AST and AST/ALT levels. The significance
      of the metabolic changes found in the red blood cells in the pathogenesis and
      clinical picture of GMI and purulent meningitis is discussed in the paper.

PMID- 8999665
TI  - [Spontaneous biochemiluminescence in serum and urine in clinical analysis and
      under experimental conditions].

PMID- 8999666
TI  - [The use of nested polymerase chain reaction method for rapid detection of
      cytomegalovirus in peripheral blood leukocytes of patients after bone marrow
      transplantation].
AB  - Nested polymerase chain reaction was used for rapid detection of human
      cytomegalovirus in blood samples of patients subjected to bone marrow
      transplantation. Use of the four-primer system appreciably improved the
      sensitivity and specificity of the method and helped eliminate the difficulties
      arising in the detection of various viral strains with the minor nucleotide
      substitutes in the DNA template. The proposed method is a reliable tool for the
      early diagnosis of cytomegaloviral viremia and for monitoring the efficacy of
      antiviral therapy.

PMID- 8999668
TI  - [Molecular characteristics of tick-borne encephalitis virus from the Southern
      Sikhote-Alin endemic region].
AB  - Molecular characteristics of 38 strains of tick-borne encephalitis (TBE) virus
      isolated in the Southern Sikhote-Alin focus were studied using 10 synthetic
      oligonucleotide probes complementary to the genomic RNA of the Sofyin strain. The
      isolated strains were divided into 4 groups, depending on the source of
      isolation: 1) strains isolated from Ixodes persulcatus (n = 8); 2) from the brain
      of patients dead from TBE (n = 10); 3) from the blood of patients with the
      febrile form of TBE (n = 7); and 4) from the blood of patients with an unapparent
      infection (n = 13). The total level of hybridization in the four groups was as
      follows: 61.8, 75.2, 55.8, and 35.2%. The "tick" strains with a great variety of
      the genofund are regarded as the stock group of the natural TBE virus population,
      40% of which are strains close by their characteristics to avirulent strains of
      TBE virus.

PMID- 8999667
TI  - [Immunochemical properties and specificity of monoclonal antibodies against N-
      and C-terminal sites of the recombinant protein of the nucleocapsid of hepatitis
      C virus (HCcAg)].
AB  - Highly affine murine monoclonal antibodies (MAB) to recombinant nucleocapsid
      (core) protein of hepatitis C virus (rHCcAg) expressed in E. coli were obtained.
      The MABs were analyzed by solid-phase enzyme immunoassay (EIA), immunodot,
      immunoblotting, and competitive immunochemical analysis. For estimating the
      epitope specificity of MAB, several immunoreactive fragments of different length
      were cloned from the HCcAg region overlapping 160 N-terminal amino acid (a. a.)
      residues. Use of these fragments and the competitive EIA demonstrated that MAB
      recognize 4 non-overlapping epitopes, 2 of which are localized in the 1-80 a. a.
      and 2 other in the 80-150 a. a. regions. A protocol of EIA for detecting HCcAg
      using MABs to two nonoverlapping HCcAg epitopes has been designed. The
      sensitivity of double-site sandwich is 1 ng/ml for the recombinant protein.

PMID- 8999670
TI  - [Constructing the reference panel of sera with standard level of IgG-antibodies].
AB  - Fundamentals of designing reference panels of sera for effective control of
      commercial test systems and immunoblotting, intended for detecting antiviral
      antibodies, have been developed. Reference low-titer panels of anti-IgG
      antibodies to HIV-a and hepatitis C virus have been designed. A reference panel
      contains diluted reactive sera with a standard level of IgG antibodies and native
      sera with undetectable level of antibodies to the major viral antigens from risk
      group subjects. The reactive sera of a panel contain the whole spectrum of
      antibodies to all principal viral antigens.

PMID- 8999669
TI  - [The study of protective properties of attenuated strain of Argentinian
      hemorrhagic fever].
AB  - Immunization of BALB/c, C57BL/6, CBA/calac mice with strain XJ44 of Argentine
      hemorrhagic fever resulted in changes of nonspecific immunity parameters, such as
      interferon, interleukin-1, tumor necrosis factor, and natural killers. The
      formation of a specific humoral and cellular immune response in BALB/c mice
      immunized with this strain has been demonstrated. Immunization of BALB/c mice
      with strain XJ44 protected the animals from infection with a heterogeneous strain
      Carvallo of Bolivian hemorrhagic fever.

PMID- 8999671
TI  - [The frequency of antibodies against delta virus in patients with HBs positive
      hepatitis].
AB  - Patients with HBsAg-positive hepatitis were screened for antibodies to HDV and
      HCV. The incidence of anti-HDV was 12.5% in a sample of 265 patients. The values
      differed appreciably in men and women, patients with chronic and acute hepatitis,
      narcomaniacs and subjects taking no narcotics. Antibodies to HDV were more
      incident in anti-HCV-positive than in anti-HCV-negative patients. The age
      specific structure of the sampling has been analyzed and the distribution of HDV,
      HCV, narcomania, and chronic hepatitis markers for age groups has been
      determined. A high incidence of mixed (double and triple) infections with
      hepatotropic viruses has been revealed.

PMID- 8999672
TI  - [Russian recombinant vaccine against hepatitis B (results of controlled trials)].
AB  - Two yeast recombinant vaccines were compared: the Russian hepatitis B Combiotech
      vaccine in a dose of 20 mg and the Recombivax-HB vaccine in a dose of 10 mg
      manufactured in the USA (Merk, Sharp and Dohme Ltd.). Both agents were found safe
      and low reactogenic. After a course of 3 vaccinations with the Russian vaccine
      92.5 to 97.5% subjects vaccinated after the 0-1-2 months and 0-1-6 months
      protocols had high levels of specific antibodies. In the group vaccinated with
      the American vaccine, antibodies to HBsAg were found in the sera of 95 to 100%
      subjects. These results demonstrate high immunological activity of both Russian
      and American vaccines.

PMID- 8999673
TI  - [Disorders in the interferon system in patients with virus-associated and
      chlamydial infections].
AB  - A more than 80% incidence of herpes simplex virus, cytomegalovirus, and
      chlamydial infection was revealed in 58 patients with various gynecological
      diseases. In 50% cases the infection was mixed. An appreciable reduction of the
      gamma-interferon system was detected in 20 patients, which was caused by a
      concomitant infectious process, possibly provoking the development of the
      underlying disease. Treatment of such patients should include antiviral and
      antichlamydial therapy, as well as correction of defects in interferon
      production.

PMID- 8999675
TI  - [The role of influenza virus hemagglutinin in blood anticoagulation processes].
AB  - Influenza virus hemagglutinin (HA) possesses anticoagulant and fubrinolytic
      activities and affects such blood clotting factors as fibrinogen and factor XIII
      in vitro and in vivo. Computer analysis of HA structure of avian, animal, and
      human type 1 influenza viruses showed 1 or 2 sites of amino acid sequences
      similar to plasminogen activator. These sites proved to be highly conservative
      for each virus subtype, irrespective of the source and year of isolation of the
      strain. Evolution relationships with respect to this sign were detected between
      the studied viruses.

PMID- 8999674
TI  - [Serological and molecular-biological study of T-cell leukemia virus in
      Turkmenistan].
AB  - Seroepidemiological and molecular-biological screening of 1510 donor blood
      samples, collected from the residents of the town of Ashgabat (Turkmenistan), for
      lymphotropic virus of human T-cellular leukemia (HTLV) virus revealed one donor
      with a high level of immune response to a wide spectrum of viral proteins. Three
      donors were serologically assessed as dubious, for their sera contained
      antibodies to gag gene protein but no antibodies to env gene protein. Screening
      of family members of the donor infected with HTLV-1 revealed four more highly
      reactive carriers of HTLV-1 virus. The presence of proviral sequences of HTLV-1
      in the lymphocyte DNA of infected donor and her relatives was confirmed by
      polymerase chain reaction and subsequent Southern-blot hybridization of specific
      amplification products. Proviral sequences of gag, pol, and LTR genes were
      detected in all the cases. Short-term culturing of peripheral blood lymphocytes
      of all seropositive subjects was associated with expression of HTLV-1 structural
      proteins. Analysis of the possible routes of transmission of HTLV-1 isolated in
      Turkmenistan permits us to hypothesize an Iranian origin of the isolated virus
      strain.

PMID- 8999676
TI  - [The use of Vero (B) cell line for medico-biological preparations].
AB  - A variant of Vero cell line has been obtained, adapted to the Russian Eagle's
      medium with 8% fetal calf serum. The variant is characterized by intensive cell
      proliferation, possesses a different content of chromosomes, contains no oncogens
      and contaminants, specifically, Mycoplasma. The strain was characterized and
      certified in accordance with the WHO requirements. Inoculation (110 ampules) and
      working (100 ampules) stocks at the levels of the 170th and 178th passages were
      placed for storage in liquid nitrogen. Vero (B) cell line is sensitive to herpes
      simplex virus types 1 and 2, CMV, hepatitis A virus, recombinant variolovaccinia
      strain expressing HbS antigen, etc. The line retains its biological properties
      from passage 178 to passage 200 and is recommended for control and preparation of
      various biomedical agents, including antiviral vaccines.

PMID- 8999677
TI  - [Method of diagnosis of Epstein-Barr virus infection].
AB  - An original methodological approach to the diagnosis of Epstein-Barr virus (EBV)
      infection is proposed, consisting in the detection of viral DNA in peripheral
      blood lymphocytes using in situ DNA hybridization. EBV DNA was found in 6 (50%)
      patients with lymphomas and in 1 (33%) with infective endocarditis out of 26
      examined recipients of blood components. No EBV DNA was found in peripheral blood
      lymphocytes of 14 regular donors. Normalization of the immune status of a patient
      and use of blood components containing no EBV is the key factor in the prevention
      of EBV infection. Biohit test system for in situ hybridization of EBV DNA may be
      used for diagnostic monitoring of EBV infection and screening of blood and tissue
      donors.

PMID- 8999678
TI  - [The use of personal computers by virologists specializing in viral hepatitis].
AB  - Analysis of the tasks of a virological laboratory as regards viral hepatitis
      helped the authors validate the requirements to computer provision and develop a
      program "Hepatitis" which permits the creation of a reliable data bank on
      subjects screened for viral hepatitis, offers a comprehensive highly qualified
      analysis, and saves time needed for file registration and making reports. The
      program is addressed to virology laboratories of sanitary epidemiological,
      therapeutic, and research institutions.

PMID- 8999679
TI  - [The use of monoclonal antibodies for the study of California serogroup viruses].

PMID- 8999680
TI  - [Recombination of alpha-viruses during mixed infection in cultured cells.
      Formation of hybrid forms of RNA of Venezuelan equine encephalomyelitis virus and
      Karelian fever virus in the region of genes for nucleocapsid and envelope
      proteins].
AB  - A recombination of the genomes of VEE and KF viruses, two alphaviruses of
      different serotypes, takes place in mixed infection of chick embryo fibroblasts
      and Vero cells with vaccine strain VEE-230 and KF-9298 strain. This recombination
      resulted in the production of recombinant virions with altered antigenic
      properties. Polymerase chain reaction (PCR) rapidly and effectively detected the
      hybrid sites of the genome in recombinant viruses. Short nucleotide sequences
      (approximately 20 n. p.) of a known primary structure in the RNA genomes,
      specifically reacting with the complementary PCR primers, were chosen as genetic
      markers. These data are the first experimental validation of the probable
      recombinant formation of alphaviruses in nature. They are in good agreement with
      findings of the recombinant structure of Western equine encephalomyelitis virus
      genome.

PMID- 8999681
TI  - [Comparative analysis of primary structure of nucleocapsid protein from Western
      equine encephalomyelitis virus and other alphaviruses].
AB  - Part of WEE virus (strain 16310-5614) genome coding for the nucleocapsid (C)
      protein was cloned and sequenced in two independent clones. The C gene of WEE
      virus is composed of 77 nucleotides, both for the BFS and 16310 strains, and is
      48, 24, 33, 15, 3, and 3 nucleotides shorter than that of Venezuelan equine
      encephalomyelitis (VEE), Semliki Forest, Ross River, Sindbis, O'Nyong-Nyong, and
      Eastern equine encephalomyelitis (EEE) viruses, respectively. It contains 16
      nucleotide changes in comparison with the BFS-1703 strain, four of which are
      significant: Ser57(BFS)-->Ala(16310), Gly63-->Cys, Lys74-->Glu, Gly97-->Trp.
      Amino acid composition, charges, hydropathic profiles, and location of potential
      functional sites in C proteins of the heretofore studied alphaviruses have been
      compared. High positively charged N-domain of the nucleocapsid is the most
      variable in all alphaviruses and is characterized by an irregular secondary
      structure due to high Pro content (25.5%). Positively charged Lys (10.8% of
      total) and Arg (6.9% of total) are presented 18 and 11 times, respectively, in
      the N-domain of WEE virus (16310) protein, and clusters thereof possibly form the
      initial sites for interaction with RNA. Only Sindbis virus (HRSP and Ock)
      nucleocapsids do not contain Cys, while others do contain several residues. This
      part of C protein includes overlapping nuclear transport signals predicted for
      several cellular proteins and repeated 4, 7, and 2 times in WEE, EEE, and Sindbis
      viruses, respectively. There is a highly conservative region (96-113 as residues)
      in the C protein structure of all studied alphaviruses, which potentially binds
      to a large ribosomal subunit as it was shown for Sindbis virus by Wengler et al.
      (1992), and a consensus motif K/R95-P-X-K/R-X-R-M could be a main part of the
      nucleoprotein ribosome binding site. The W186HHGAVQ (WEE virus) is absolutely
      conservative for all alphaviruses and with the invariant Asn222 could have a
      common function, including C protein lateral interaction (Choi et al., 1991). The
      origination of WEE virus C protein from EEE virus is confirmed by very high
      (92.7%) similarity of this protein's C domain in the WEE/EEE pair and low (64.8%)
      in the WEE/Sindbis pair. Determination of C gene and protein type in the
      Sindbis/WEE virus serocomplex might be useful in the differential identification
      of this virus group.

PMID- 8999682
TI  - [Antigenemia in people infected with tick-borne encephalitis virus].
AB  - An original modified method of tick-borne encephalitis (TBE) diagnosis was used
      to examine 1196 subjects. It is shown that tick bites frequently lead to TBE
      virus infection in all the age groups (24.9 +/- 1.3%). Antigenemia in febrile TBE
      form occurred in 45.8 +/- 6.0%, in severe form in 19.3 +/- 4.2% of cases.
      Children with the highest viremia and antigenemia are considered as an indicator
      system of TBE virus infection rate in the population in different seasons.
      Population of TBE virus consists of 2 parts. The prevalent part is inapparent and
      does not induce manifest infection. The other part of the virus population with
      similar seasonal activity gives rise to severe clinical forms of TBE with lethal
      outcomes.

PMID- 8999683
TI  - [A system of immunoenzyme analysis using biotinylated monoclonal antibodies for
      typing hantavirus antigens].
AB  - Enzyme immunoassay with biotin-labeled monoclonal antibodies to Puumala virus was
      used for typing hantavirus antigens. The system is type-specific, that is, it
      detects Puumala virus only, which was demonstrated by typing 9 hantavirus
      antigens in infected Vero E5 cells and by epizootological analysis of an HFRS
      outbreak in the Yegoryevsk district of the Moscow region in November-December
      1995. The suggested system may be used as an element of EIA screening of natural
      samples in analysis of the screening results.

PMID- 8999684
TI  - [Virus carriers in rotavirus infection].
AB  - Discusses the effects of various factors on the expression of asymptomatic virus
      carriership and validates the need in laboratory screening of risk groups
      including children aged under 5 years and elderly subjects aged over 60. During
      outbreaks of rotaviral infection virus carriership among healthy subjects may be
      as high as 34.6%.

PMID- 8999685
TI  - [Development and application of immunoenzyme test-system for the diagnosis of
      acute cytomegalovirus infection].
AB  - Enzyme immunoassay for the detection of IgM antibodies to human cytomegalovirus
      (CMV) has been developed. Use of horseradish peroxidase conjugated monoclonal
      antibodies to human IgM helped create a highly specific test system. The
      rheumatoid factor was removed from the serum by staphylococcal reagent containing
      protein A. The results of the newly developed assay are in good correlation with
      the clinical course of the disease and data of polymerase chain reaction and the
      test making use of the Labsystem. Cytomegalovirus IgM EIA Kit.

PMID- 8999686
TI  - [Efficacy of herpetic vaccine, larifan, myelopid and their combinations during
      herpesvirus infection in irradiated animals].
AB  - Killed vaccine against herpes simplex virus (HSV) 1 and 2, interferon inducer
      larifane, immunostimulant myelopide, and their combinations were sufficiently
      effective in immunocompromized mice inoculated intraperitoneally with HSV-1 and
      HSV-2 three days after a single radiation exposure. Combinations of the vaccine
      with myelopide or larifane had a higher protective effect than that of each of
      these agents alone. All of these drugs and their combinations more rapidly
      reduced the concentrations of the virus antigen in the organs of exposed and
      infected animals, although did not completely eliminate the virus, improved the
      cell-mediated and humoral immunity, thus improving their survival and prolonging
      the life span; moreover, they alleviated some immunosuppressive effects of
      ionizing radiation.

PMID- 8999687
TI  - [Stability of Marburg virus to lyophilization process and subsequent storage at
      different temperatures].
AB  - The data on Marburg virus resistance to freeze-drying in the presence of
      protective media and on a decrease in the freeze-dried virus biological activity
      at positive and negative temperatures are presented. Using the results of the
      experiments, kinetic parameters of virus thermoinactivation were determined for
      long-term storage at 20 and 37 degrees C. The rate of Marburg virus inactivation
      was comparable to the rates reported in the literature for para-, mixo- and toga
      viruses. The conclusion is made on feasibility of prolonged storage of Marburg
      virus under negative temperatures.

PMID- 8999688
TI  - [Comparative evaluation of test-systems for detection of Venezuelan equine
      encephalomyelitis virus and variola virus using dot immunoenzyme assay and solid
      phase lanthanide immunofluorescent assay].
AB  - The sensitivity and specificity of 4 experimental test systems for dot enzyme
      immunoassay (dot-EIA) and solid-phase lanthanide immunofluorescent analysis (SP
      LIFA) were studied with Venezuelan equine encephalomyelitis (VEE) and
      variolovaccinia viruses. Test systems for SP LIFA proved to be 25 times more
      sensitive than those for dot-EIA. The test systems were highly specific and did
      not react with the heterologous viruses and proteins. Diagnostic agent for
      detecting VEE virus in dot-EIA was false-positive with Sindbis virus in low
      dilutions. The first trials of the Russian test systems for dot-EIA and SP LIFA
      showed that these systems rapidly and reliably detect VEE and variolovaccinia
      viruses in liquid samples.

PMID- 8999689
TI  - [Collection of pathogenic viruses: state of the problem and prospects].
AB  - The organizational and methodological separateness in the collection of
      pathogenic viruses impedes the development of universal approaches to practical
      collection. The authors propose a universal research program for the creation of
      specialized National Museums of Pathogens as reference and methodological centers
      within the framework of the Russian State Collection of Microorganisms. Further
      improvement of methods for virus collection is desirable.

PMID- 8999690
TI  - [Propafenone, flecainide, procainamide in the treatment of a fresh attack of
      atrial fibrillation].
AB  - The purpose of the present work was an assessment of the effectiveness of
      intravenously administered propafenone, flecainide and procainamide in
      restoration of sinus rhythm in patients with atrial fibrillation attack lasting
      not more than 48 hours, The studies were carried out in 95 patients, including 30
      treated with propafenone, 27 with flecainide, and 38 with procainamide.
      Propafenone turned out to be effective in 23 patients (76.7%), flecainide in 19
      patients (70.4%), and procainamide in 14 patients (36.8%). Each of the drugs more
      effectively restored sinus rhythm in patients with smaller size of the left
      atrium and with shorter duration of atrial fibrillation attack, and propafenone
      and flecainide were also more effective in younger patients. The return of sinus
      rhythm was accompanied a reduction of the size of the left atrium. None of the
      studied drugs caused any more important adverse effects.

PMID- 8999691
TI  - [Digoxin level as a limited drug toxicity indicator in the assessment of post
      digitalis arrhythmia].
AB  - A clinical-laboratory analysis was carried out in 18 patients on long-term
      treatment with digoxin in whom toxic arrhythmia occurred, taking into account
      serum digoxin level measurement. In 11 patients the toxic arrhythmia correlated
      with high digoxin concentration in blood, in six cases it was observed with the
      concentration of the drug within the therapeutic level range, and in one patient
      it was seen below this range. Blood digoxin level in patients with hypokalemia
      was significantly lower in comparison to those with normal serum potassium level.
      Severe clinical condition of patients, especially elderly persons with
      hypokalemia, respiratory acidosis and renal failure contributes to the
      development of toxic arrhythmia; for this reason it is useful to apply in these
      patients the therapy monitored by blood level of the drug. Electrocardiographic
      features of digitalis action and non-cardiac adverse effects were seldom observed
      in patients with toxic arrhythmia.

PMID- 8999692
TI  - [Holter EKG method of monitoring during gastroscopic examination in children].
AB  - Assessing the results of ECG monitoring by the Holter method during gastroscopic
      examination in children a more frequent incidence was found of isolated
      ventricular ectopic beats than in the control group. No complex forms of
      arrhythmia were found in either group.

PMID- 8999693
TI  - [Preliminary evaluation of the usefulness of passage time along the alimentary
      tract in the diagnosis of constipation in children].
AB  - In children with constipation the usefulness of passage time along the large
      bowel was assessed, limiting the number of performed rectal enemas. The
      preliminary results suggest that it is possible to answer the clinician's
      questions - whether the passage time is prolonged, and if so, to determine in
      what segment of the large bowel. This method may be treated as a screening test
      in the diagnosis of constipation in children.

PMID- 8999694
TI  - [Thyroid anti-membrane antibodies and antithyroglobulin antibodies of children in
      the city and province of Wroclaw].
AB  - The purpose of the work was an assessment of thyroid function and determination
      of the development of antithyroid autoantibodies in children undergoing iodine
      prophylaxis after Chernobyl disaster. The level of T3 and T4 was determined by
      the RIA method, that of TSH by th immunoenzymatic method using Abbott kit, while
      antimembrane and antithyroglobulin antibodies were determined by the
      immunoenzymatic method using HTL-Plastomed kit. The studies were carried out in
      844 children (433 boys and 411 girls) aged from 4 to 16 years, the selection of
      whom was described in our earlier report (12). Our studies demonstrated an
      increased level of T3 in 15.6% of the studied children and increased level of T4
      in 12.7% of the cases. In most children the levels of hormones and TSH in the
      serum were normal. The antimembrane antibodies ATMA were present in 1.9% of the
      children (0.5% of the boys and 3.4% of the girls), while antithyroglobulin
      antibodies were found in 2.2% of the studied population (0.9% of the boys and
      3.4% of the girls). No correlation was found between clinical picture, size of
      goitre, hormone level and the presence of thyroid autoantibodies. The studies
      indicate that radioactive contamination and iodine prophylaxis failed to cause
      permanent thyroid function disturbances in the studied population. The children
      in whom autoantibodies or abnormalities in hormone levels were found require
      further observation.

PMID- 8999695
TI  - [Torsion of the testicle and testicular adnexa in children].
AB  - Between 1987-May 1994 the treatment results of 73 boys with the symptoms of
      "acute scrotum" were presented. 67 boys were operated. During the operations in
      14 cases the torsion of testicle were observed, in 2 cases necrotically changed
      testicles were removed. Among 53 boys torsion of the appendices of the testis
      were observed, the appendices were removed. 6 boys with the diagnosis of torsion
      the appendices of the testis were conservatively treated with a good result. On
      the basis of literature review and own experiences the children should be
      qualified for operation by the anamnesis and physical examination independently
      from additional and sonography results. The acute symptoms of scrotum or inguinal
      canal in the absence of the testicle in scrotum should indicate at the need for
      early surgical intervention in case of acute symptoms concerning testicles and
      scrotum. The epididimitis and orchitis is rare with children before pubescence.
      One child with the epididimitis abscess, the epididimis was removed.

PMID- 8999696
TI  - [Biliary gastritis after partial gastrectomy by the Maki method].
AB  - An assessment was carried out of 93 patients operated on in the years 1977-91 in
      the Surgery Department of the hospital in Jaslo for gastric ulcer by Maki method.
      The assessment included the incidence of the so called "biliary gastritis". It
      was carried out on the basis of history taking, endoscopic and histopathological
      examinations. Surgical operations were performed by two methods: the first
      included sparing of pyloric innervation, the other was without sparing. In the
      group with sparing of innervation (33 studied subjects) no changes of biliary
      gastritis character were found. In the group without sparing (58 patients),
      biliary gastritis was found in 14 cases (24.1%) which was a statistically
      significant difference. The applied modification of Maki operation with sparing
      of pyloric innervation is presented.

PMID- 8999697
TI  - [The risk of surgical treatment in elderly patients].
AB  - The course of surgical treatment of 124 patients aged over 70 years was subjected
      to an assessment. On the basis of the ASA classification, 88% of all surgically
      treated patients fell into group III-IV of risk. Surgical operations were
      performed under intratracheal general anaesthesia (85%) or conduction anaesthesia
      (15%). The induction of general anaesthesia was accompanied by adverse reactions
      of the cardiovascular system in the form of arterial blood pressure drops and
      heart rhythm disturbances. Heart rhythm disturbances were not observed in
      patients under conduction anaesthesia. No intraoperative deaths were noted.

PMID- 8999698
TI  - [Cancer and pathologic hyperplasia of endometrial mucosa. Clinical study].
AB  - The authors carried out a tentative evaluation of the factors regarded as
      increasing the proneness to endometrial cancer development. Particular attention
      was paid to pathological hyperplasia of the endometrium. The studied material
      consisted of 592 women (76 with endometrial cancer and 516 with endometrial
      hyperplasia). The incidence of pathological hyperplasia of the endometrium was
      six times higher than that of endometrial cancer. Endometrial cancer was found
      mainly in postmenopausal women. Apart from pathological hyperplasia of the
      endometrium, among other factors characterizing women developing endometrial
      cancer, hypertension should be mentioned in the first place. In the postoperative
      material obtained from women operated on for endometrial cancer (76 cases) and
      pathological endometrial hyperplasia (244 cases) the character of pathological
      changes in removed ovaries in 2/3 of the cases pointed to hyperplastic non
      malignant lesions. In 1/3 of the women either no pathological changes or only
      fibrosis and ovarian tissue atrophy were found in the ovaries.

PMID- 8999699
TI  - [The place of galactography in the diagnosis of secreting mamma].
AB  - Examinations were carried out in 3,300 women, finding in 210 cases a spontaneous
      or provoked discharge from one or two breasts. Out of these women 115 patients
      came for galactographic examination. After the radiological examinations 37
      patients were treated surgically including 28 cases with the diagnosis of
      intraductal hyperplasia, and in this group of patients histopathological
      examination demonstrated: nine cases of cancer, seven cases of papilloma, seven
      cases of fibroadenoma, seven cases of benign dysplasia with ductal epithelial
      hyperplasia, three cases of inflammatory lesions, and one case without
      pathological changes. The analysis carried out demonstrated that galactographic
      picture of secreting ducts may suggest a hyperplastic process but determination
      of its character is possible only in histopathological examination.

PMID- 8999700
TI  - [Coenzyme Q--clinical significance].
AB  - In the paper the clinical importance is presented of the use of coenzyme Q
      (ubiquinone) preparation. On the basis of available literature the participation
      of coenzyme Q was determined in the pathogenesis and aetiology of a number of
      diseases, e.g. diseases of the circulatory system, locomotor system, diabetes
      mellitus, obesity or endocrine system diseases.

PMID- 8999701
TI  - [The place of fibronectin in hepatologic diagnosis].
AB  - In the paper the structure, place od synthesis and biological role of fibronectin
      in human organism are discussed, and the value of plasma fibronectin (FN)
      concentration determination in the diagnosis of chronic hepatic diseases,
      including hepatic fibrosis, was critically evaluated. Simultaneously, the view is
      presented that the determination of FN concentration in peritoneal fluid, as well
      the determination of amount and location of FN in the hepatic tissue should be a
      routine element of hepatological diagnosis.

PMID- 8999702
TI  - [Small intestine transplantation in the human--clinical studies].
AB  - Three stages in development of small bowel transplantation (SBT) in a human are
      discussed. Indications to SBT in adults and children are mentioned. Clinical
      experiences in SBT in humans with particular presentation of actual problems,
      difficulties and future of SBT are discussed.

PMID- 8999703
TI  - [Possibilities for taking advantage of fish oil in obstetrics].

PMID- 8999704
TI  - [The effect of laser radiation on biological tissue].

PMID- 8999705
TI  - [Simplified estimate of taxon genetic differentiation by the electrophoretic
      spectra of tissue proteins exemplified by bats (suborder Microchiroptera)].

PMID- 8999707
TI  - [Organ preserving and reconstructive procedures in gynaecological oncology.
      Proceedings of a workshop. Heidelberg, October 12-14, 1995].

PMID- 8999706
TI  - [Long-term results of organ preserving therapy in ovarian carcinoma].
AB  - Conservative surgery is of increasing importance in gynecologic oncology.
      Criteria for conservative surgery are well defined, in spite of this a lot of
      young women with early ovarian cancer are treated with radically operative
      procedures. Data of 17 patients below the age of 35 with stage I ovarian cancer
      and conservative surgery are reported. Only one of 9 patients with epithelial
      carcinoma relapsed and could be successfully treated with surgery and
      chemotherapy. No patient died within a median follow up of 8 years. All patients
      demonstrated intact endocrine function after conservative surgery.

PMID- 8999708
TI  - [Tumor-adapted oncoplastic mastopexy and reduction-plasty].
AB  - Reduction mammaplasties can be performed--if contraindications are respected--as
      oncoplastic operations. They have the advantage that the lump has clear margins
      and is surrounded by a thick layer of healthy tissue. This works only under the
      condition that the right type of the different mammaplasties is chosen as to
      cancer site, which guarantees that the cancer part of the breast will be removed
      ("landmap of removed breast tissue"). The axillary cavity must be cleared and the
      oncoplastic (reconstructed) breast be irradiated with 50 Gy. The mastopexia
      (breastlifting) is less apt to be used as an oncoplastic operation, as the
      removed tissue is rather skin and subcutaneous fatty tissue than the breast gland
      itself.

PMID- 8999709
TI  - [Diagnostic value of Doppler ultrasound in evaluation of breast tumors].
AB  - Angiogenesis is an essential condition for tumor growth. Therefore, it seems to
      be of interest to prove if blood flow and vascularization of breast tumors give
      information concerning their dignity. Consequently, 205 patients with palpable
      and/or mammographically detected breast tumors were examined prior to surgery by
      doppler sonography for blood flow in the area of the tumor. In 174 patients of
      this group the corresponding area of the contralateral breast was also screened
      by doppler ultrasound. With third doppler generation angiodynography tumors can
      be visualized as B-images with simultaneous information on vascularization. An
      integrated doppler system shows the detected blood flow in form of a doppler
      curve, also allowing quantification according to doppler criteria (Resistance
      Index RI). Blood flow detection in the tumor itself was successful in 71% of all
      malignancies, whereas in only 6.6% of the 76 benign lesions (n = 5) blood flow
      was found in the central tumor area. In the area surrounding the tumor blood flow
      was detected in 83% of all carcinomas, but only in 29% of benign findings. Blood
      flow could be detected significantly higher in malignancies than in benign
      lesions (p = 0.003). Blood flow detection in the tumor itself was a highly
      specific (93%) method of discrimination between malignant and benign breast
      tumors. Further quantification by means of doppler parameters only increases
      insignificantly specificity, quantification of blood flow in the area surrounding
      the tumor using the RI and the comparison with the contralateral breast could
      improve the diagnostic value as our findings RI < 8 for benign vs. > or = 8 for
      malignant lesions demonstrated. Detection of malignant tumors showed a
      sensitivity of 80%, a specificity of 90%, and a positive predictive value of 93%.
      In patients with breast cancer (histologically confirmed) the detection rate of
      blood flow in tumors and surrounding areas was independent of tumor size or nodal
      status.

PMID- 8999710
TI  - [Prognostic significance of p53 autoantibodies in serum of patients with breast
      carcinoma].
AB  - Mutations in the p53 tumor suppressor gene are the most common genetic
      alterations associated with malignant tumors including breast and gynecologic
      carcinomas. Overexpression of p53 protein is a result of increased protein
      stability caused through conformationally alteration. Accumulation of mutant p53
      in tumor cells may lead to a humoral immune response with development of p53
      autoantibodies. In the present study we investigated the sera of 72 patients
      undergoing surgery for primary breast cancer and the relation between p53
      antibody production, prognostic parameters and clinical outcome. Circulating p53
      antibodies were detected in 15 of the 72 examined patients (21%). A correlation
      to conventional prognostic factors was not observed. Yet the overall survival was
      worse in patients with p53 antibodies (p < 0.04), suggesting a more aggressive
      tumor type.

PMID- 8999712
TI  - [Response evaluation with mammography and ultrasound].

PMID- 8999711
TI  - [Response evaluation with functional magnetic resonance mammography].

PMID- 8999713
TI  - [High dose chemotherapy: an overview in ovarian carcinoma].

PMID- 8999714
TI  - [Principle and foundations of high dose therapy with stem cell transplantation].

PMID- 8999715
TI  - [Immunotherapy in gynecologic oncology].

PMID- 8999716
TI  - [New drugs. Topoisomerase inhibitors].

PMID- 8999717
TI  - [Taxol].

PMID- 8999718
TI  - [Ifosfamide].

PMID- 8999719
TI  - [Bisphosphonates in anti-osteolytic therapy of metastasizing breast carcinoma].
AB  - Bisposphonates are pyrophosphate analogues and in the human organism are
      similarly bound to hydroxlapatite. By various mechanisms, bisphosponates inhibit
      the activity of the osteoclasts. Due to this characteristic feature they are
      exceptionally well suited to prevent bone destruction. Breast cancer is often
      complicated by skeletal metastases, associated with such typical complications as
      pain, pathologic fractures, hypercalcemia, aso. Bisphosphonates, in an adequate
      dose, reduce the rate of skeletal complications. The present publication is an
      overview on pharmacological aspects and therapeutic indications of
      bisphosphonates. Therapeutic guidelines on dosage and duration of therapy are
      given for individual indications. The palliative character of these substances is
      underlined and antiosteolytic treatment is described as the third pillar (beside
      hormone and chemotherapy) of systemic therapy of breast cancer with bone
      metastases. Subsequently, the most common side effects and complications are
      described. Bisphosphonates have osteoprotective characteristics and, possibly,
      could play a role in prophylaxis of ossary metastases.

PMID- 8999720
TI  - [Oral idarubicin in treatment of advanced breast carcinoma].
AB  - Idarubicin is the first anthracycline derivative which can be applied orally due
      to its high lipid solubility. The joint bioavailability of the parent compound
      and its active metabolite Idarubicinol is around 40%. The most frequently used
      administration schedule is 45 mg/m2, day 1 or 15 mg/m2, day 1-3 every third or
      forth week. The dosis for weekly administration is 15-20 mg/m2. The objective
      remission rate of the pooled data of 509 evaluable patients treated with the q3w
      schedule is 24% (CR 3%, PR 21%). The most important side effects are reversible
      leukopenia and moderate gastrointestinal toxicity. The cardiac toxicity and
      alopecia are significantly lower than that observed by doxorubicin or epirubicin
      treatment.

PMID- 8999721
TI  - Regulation and function of adhesion molecules in B-cell chronic lymphocytic
      leukaemia.
AB  - Cell surface expression of adhesion molecules in B-cell chronic lymphocytic
      leukemia (B-CLL) may determine the patterns of dissemination and infiltration. B
      CLL cells express high levels of CD44, but expression of the leucocyte integrins
      was low or absent, while expression of VLA-4 is high. Most cases examined
      expressed no detectable ICAM-1, but some cases demonstrated levels of up to 30%.
      Levels of L-selectin were also variable, and expression could be induced/enhanced
      in vitro by incubation with cytokines such as IL-4, interferon-alpha and
      interferon-gamma. B-CLL cells bound normally to vascular endothelium, but binding
      to IL-1-activated endothelium was significantly lower than that of normal
      peripheral blood lymphocytes. Cytokine enhancement of L-selectin expression was
      not accomplished by changes in binding to vascular endothelium. Patterns of
      adhesion molecule expression and their regulation by cytokines may underly some
      of the clinical features of this disease.

PMID- 8999723
TI  - [A prospective study of patient with schizophreniform disorder: a nosological
      dilemma?].
AB  - We study retrospectively 42 inpatients of the psychiatry department of the Ramon
      y Cajal Hospital, through a period between 1st January of 1988 and the 31st
      December 1993. All of them were diagnosed at discharge of schizophreniform
      disorder according to DSM-III R diagnostic criteria and it was in all of them the
      index episode of the psychosis. Sociodemographic, clinical, evolutive, and
      therapeutical variables are analyzed. We made a new assessment of the patients in
      the sample during April 1994 through a direct interview. The mean follow-up
      period was 4.18 years. The main results were: A predominance of male/female
      proportion (2/1), nearly half of the sample had emotional or psychosocial
      stressors previous to the episode. Previous schizoid personality traits were
      found in 57.1%. 11.9% had first degree relatives antecedents of schizophrenia and
      19% of non-bipolar affective disorders. At follow-up 40.4% needed to be
      hospitalized again. It is noteworthy that 80.9% were rediagnosed during follow-up
      as schizophrenia.

PMID- 8999724
TI  - [Seasonality and psychiatric emergencies].
AB  - The purpose of this study is to analyze the seasonality of the psychiatric
      emergencies visited in a casualty department, prospectively, during twelve
      consecutive months. The data were obtained with a record card containing clinics,
      sociodemographics, and related to consulting moment variables. During the months
      comprised between June to September, the results showed a general increase on the
      majority diagnostics and/or syndromics consulting reasons, with mention special
      to affective disorders. The increase showed in these entities could be related
      with the summer increase in Avila population. Because of these reason, these
      results, over all, those referred to July and August, should be interpreted with
      caution. These and other considerations are commented on the discussion.

PMID- 8999722
TI  - [Alcohol dependence and psychiatric comorbidity. I. Epidemiology and
      etiopathogenic involvement].
AB  - We revise the articles dealing with psychiatric comorbidity of alcohol
      dependence. This study focuses on the epidemiology and on the etiopathogenic
      involvement. The epidemiologic studies in community samples show that psychiatric
      comorbidity in alcohol dependence is twice as big as expected and this excess is
      common in every psychiatric disorder. However, this excess is bigger in
      antisocial personality, other substance-related disorders and in schizophrenia.
      This excess of comorbidity can be due to two factors: how alcohol can cause
      psychiatric disorders, and how psychiatric symptoms can produce an increases of
      alcohol consumption which can lead to dependence in people with vulnerability.

PMID- 8999726
TI  - [The scientific origin of ECT: a conceptual history].
AB  - This paper deals with the scientific origins of the electroconvulsive therapy,
      particularly between 1938 and 1945. The most interesting and imaginative research
      on ECT occurred in this period. An analysis of a host of social, moral and
      scientific factors to understand its history is offered, focusing on several
      european countries.

PMID- 8999725
TI  - [Parenchymal neurosyphilis. Insidious onset (dementia) and acute onset (manic
      type) forms].
AB  - The increased rates in recent years of primary and secondary syphilis, with a
      renovated interest of central nervous system infection by the treponema pallidum,
      justify the presentation of two cases of classic General Paresis: Dementia and
      Mania. Both patients fulfilled sufficient criteria as to elaborate a process of
      differential diagnostic of physical illness in patients with mental disorders,
      which include a battery laboratory tests. The positive response to a protocol
      with penicillin improved both the clinical symptoms and the laboratory tests.

PMID- 8999727
TI  - [The logical basis of mental confusion in Delasiauve, Bonhoeffer and Llopis
      versus DSM-III-R delirium].
AB  - Delasiauve, Bonhoeffer and Llopis, conceived confusional scenes contrasting the
      theory of Unique Psychosis, Nosologic Unit, and Psychical Atomism respectively.
      The a-theoric DSM-III-R, doesn't establish any new concept, limiting itself to
      arrange in other way, that which was discovered by those and others authors,
      without rational justifications, having priority over clinical considerations,
      verbal definitions, with a practice and scientific value that may be debatable.

PMID- 8999729
TI  - Proceedings of the 39th OHOLO Conference on Vaccines: Novel Strategies in Design
      and Production. Eilat, Israel, May 7-11, 1995.

PMID- 8999728
TI  - [Psychological approach to headaches in children and adolescents].
AB  - The headache's concept in children and adolescents is updated. The author exposes
      an prevalence rate research and the clinical assessment approach in the
      Paediatric setting. An psychological perspective is exposed from a developmental
      and psychodynamic approach. The case management from Paediatric's setting
      includes: clinical assessment, psychological and developmental contents, family
      counselling and an methodological approach to refer they to Child and Adolescent
      Psychiatric Services.

PMID- 8999731
TI  - [A case of ureteropelvic junction stenosis accompanied by a valve-like structure
      in the renal pelvis].
AB  - A 9-year-old girl visited our clinic with recurrent high fever as her chief
      complaint. Her excretory urogram showed only a few dilated upper calyces.
      Retrograde pyelography revealed ureteropelvic junction stenosis with
      hydronephrosis, so that the ureteral catheter could not be passed through the
      ureteropelvic junction. A fold-like filling defect was also seen above the
      ureteropelvic junction. At operation the ureteropelvic junction was found to be
      markedly obstructed, and a semilunar valve-like structure was also observed above
      it. The valve-like structure was seen where the fold-like filling defect appeared
      on the retrograde pyelogram. En bloc resection of the lower part of the renal
      pelvis with the valve-like structure and the ureteropelvic junction was
      performed, followed by dismembered uretero-pyeloplasty. Histologically, the valve
      like structure was a transverse mucosal fold with a muscle layer and without
      adventitia. Many cases of ureteral valves have been reported, but none with
      valves or valve-like structures within the renal pelvis as in our case.

PMID- 8999730
TI  - Renal leiomyoma: a case report.
AB  - We report a case of renal leiomyoma. A 46-year-old woman was found incidentally
      to have a solid and cystic renal mass on computerized tomography. The angiogram
      revealed no neovascularity. Nephrectomy was performed. Histologically, it was
      diagnosed as renal leiomyoma of vascular type. Although preoperative diagnosis of
      renal leiomyoma is difficult due to the various radiological findings, we should
      always consider this tumor in the differential diagnosis of renal tumors.

PMID- 8999732
TI  - My first year on the job. The mission at home.

PMID- 8999733
TI  - My first year on the job. You stole my tongue.

PMID- 8999734
TI  - Staff nurses at work. My first year on the job: she works hard for the money.

PMID- 8999735
TI  - My first year as a nurse. Daughters of Miriam.

PMID- 8999736
TI  - Compensation of medical examiners for telephone calls.

PMID- 8999737
TI  - Polymeric mercaptosilane-modified platinum electrodes for elimination of
      interferants in glucose biosensors.
AB  - An oxidase-based glucose sensor has been developed that uses a mercaptosilane
      modified platinum electrode to achieve selectivity of electrochemical
      interferants. A platinum-iridium (9:1) wire (0.178 mm o.d., sensing area of 1.12
      mm2) is modified with (3-mercaptopropyl)trimethoxysilane. The modified sensors
      show excellent operational stability for more than 5 days. Glucose oxidase is
      immobilized on the modified surface (i) by using 3-maleimidopropionic acid as a
      linker or (ii) by cross-liking with bovine serum albumin using glutaraldehyde.
      Sensitivities in the range of 9.97 nA/mM glucose are observed when the enzyme is
      immobilized by method ii. Lower sensitivities (1.13 x 10(-1) nA/mM glucose) are
      observed when immobilization method i is employed. In terms of linear response
      range, the sensor enzyme-immobilized by method i is superior to that immobilized
      by method ii. The linearity is improved upon coating the enzyme layer with
      polyurethane. The sensor immobilized by method ii and coated with polyurethane
      exhibits a linear range to 15 mM glucose and excellent selectivity to glucose
      (0.47 nA/mM) against interferants such as ascorbic acid, uric acid, and
      acetaminophen.

PMID- 8999738
TI  - Maximum entropy method for frequency-domain fluorescence lifetime analysis. 2.
      Timing, mismatched intensity, and reference lifetime errors.
AB  - The maximum entropy method (MEM) provides a robust and unbiased solution to
      fluorescence lifetime data through the use of a broad window of decay terms fit
      by simultaneous minimization of the chi 2 goodness-of-fit parameter and
      maximization of a statistical entropy function. This work investigated the
      effects of three systematic errors, common in frequency-domain measurements, on
      fluorescence lifetime recovery by MEM. Through real and simulated data, the
      expression of the systematic errors in lifetime distributions recovered by MEM
      was compared to that in standard nonlinear least-squares (NLLS) analysis.
      Reference lifetime errors in the presence of random noise had similar effects on
      both MEM and NLLS results. Characteristic changes in the recovered lifetimes,
      fractional intensities, and peak shapes were related to the identification of the
      true reference lifetime. Compared to NLLS, MEM afforded significant improvements
      for the recovery of lifetimes and fractional intensities from data containing
      timing or mismatched intensity errors. These improvements are linked to the
      dynamic, self-modeling approach of MEM and the direction provided by the entropy
      criterion. These results speak to the utility of the maximum entropy approach in
      frequency-domain fluorescence lifetime recovery as well as in other applications.

PMID- 8999739
TI  - Determination of 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and -furans at
      the part per trillion level in United States beef fat using high-resolution gas
      chromatography/high-resolution mass spectrometry.
AB  - As part of the U.S. EPA Dioxin Reassessment Program, the 2,3,7,8-chlorine
      substituted dibenzo-p-dioxins and furans were measured at part per trillion (ppt)
      levels in beef fat collected from slaughter facilities in the United States. This
      is the first statistically designed national survey of these compounds in the
      U.S. beef supply. Analyte concentrations were determined by high-resolution gas
      chromatography/high-resolution mass spectrometry, using isotope dilution
      methodology. Method limits of detection on a whole weight basis were 0.05 ppt for
      TCDD and 0.10 ppt for TCDF, 0.50 ppt for the pentas (PeCDDs/PeCDFs)/hexas
      (HxCDDs/HxCDFs)/heptas (HpCDDs/HpCDFs), and 3.00 ppt for the octas (OCDD/OCDF).
      Method detection and quantitation limits were established on the basis of
      demonstrated performance criteria utilizing fortified samples rather than by
      conventional signal-to-noise or variability of response methods. The background
      subtraction procedures developed for this study minimized the likelihood of false
      positives and increased the confidence associated with reported values near the
      detection limits. Mean and median values for each of the 2,3,7,8-Cl-substituted
      dioxins and furans are reported, along with the supporting information required
      for their interpretation. The mean toxic equivalence values for the samples are
      0.35 ppt (nondetects = 0) and 0.89 ppt (nondetects = 1/2 LOD).

PMID- 8999740
TI  - Mixture analysis using a quadrupole mass filter/quadrupole ion trap mass
      spectrometer.
AB  - A hybrid tandem mass spectrometer is constructed by interfacing a quadrupole mass
      filter (Q) to a quadrupole ion trap mass spectrometer (QITMS) and is evaluated
      for the analysis of mixtures. The mass filter is set to selectively inject ions
      of a particular m/z or, in scanning mode, to sequentially inject ions into the
      QITMS for subsequent manipulation and detection. Performance of the instrument is
      demonstrated using a mixture of ions created by electron impact ionization of
      perfluorotributylamine (FC-43) and peptide ions generated by pulsed Cs+
      bombardment. Resulting data are compared to those obtained by utilizing only the
      ion trap. Molecular weight, fragmentation, and high-resolution analyses for the
      sequentially injected mass-filtered peptides show improved performance over
      similar measurements employing only the ion trap mass spectrometer. Performance
      is optimized when ions are not rf-isolated in the QITMS. Using the hybrid, a
      resolution of 33,200 is achieved for angiotensin I. Dramatic reduction of space
      charge-induced signal suppression is demonstrated for LSIMS of Glu-fibrinopeptide
      B. 'On-the-fly' collision-induced dissociation is performed for m/z 502 from FC
      43, where fragmentation is induced by increasing the ion injection energy.
      Collision-induced dissociation efficiencies for fragmentation of angiotensin I by
      resonance excitation are investigated as a function of cooling time for different
      modes of operation of the hybrid. A current limitation of the instrument is the
      time required to port the data for acquisition.

PMID- 8999741
TI  - Analysis of tamoxifen and its metabolites by on-line capillary electrophoresis
      electrospray ionization mass spectrometry employing nonaqueous media containing
      surfactants.
AB  - On-line capillary electrophoresis-electrospray ionization mass spectrometry (CE
      ESMS) has been employed for the analysis of metabolites of the anticancer drug
      tamoxifen. Nonaqueous (methanol) CE electrolyte provided better resolution and
      detection sensitivity compared to aqueous systems or highly aqueous water
      methanol electrolyte mixtures. Nonaqueous methanol also permitted the use of
      lower ES voltages presumably owing to its lower surface tension, which
      facilitated droplet breakup. This decreased the tendency to produce electric
      discharges, thus improving the stability of electrospray conditions. The relative
      ease of methanol solvent evaporation may contribute to an improved yield of
      protonated analytes as compared to highly aqueous solutions. Enhanced CE
      resolution can be at least partially attributed to the improved solubility of
      analytes in methanol relative to water. Higher solubility implies less
      aggregation of hydrophobic analytes, thus improving homogeneity in solution.
      Moreover, electroosmotic flow toward the detector decreased in methanol relative
      to water. The reduction of this force pushing all analytes through the capillary,
      but not aiding in separation, implies that other factors such as slight
      differences in electrophoretic mobilities are more apt to lead to successful
      separations. Surfactants were employed as nonaqueous CE-ESMS buffer additives. An
      SDS concentration of 7 mM lowered the ESMS signal response for N
      desmethyltamoxifen by a factor of approximately 3. However, separation of
      tamoxifen metabolites using 7 mM SDS was augmented relative to the unadulterated
      methanol electrolyte. This enabled the separation of alpha-hydroxytamoxifen and 4
      hydroxytamoxifen, which were not resolvable in methanol electrolyte devoid of
      SDS. The methanol-surfactant electrolyte system has been successfully used to
      determine metabolites formed after incubation of tamoxifen with mouse
      hepatocytes.

PMID- 8999742
TI  - Informational orthogonality of two-dimensional chromatographic separations.
AB  - A qualitative informational similarity technique has been used to describe the
      informational orthogonality of projected two-dimensional (2-D) chromatographic
      separations of complex mixtures from their one-dimensional 1-D separations. The
      reversed-phase liquid chromatography (RPLC), supercritical fluid chromatography
      (SFC), gas-liquid chromatography (GLC), and micellar electrokinetic capillary
      chromatography (MECC) retention behavior of up to 46 solutes of varying molecular
      properties was studied by 2-D range-scaled retention time plots and information
      entropy calculations. One hundred five combinations of technique/stationary phase
      pairs were used to simulate the 2-D chromatographic analyses. The informational
      entropy of one and two dimensions, the mutual information, the synentropy or
      "cross information", and the informational similarity were calculated to describe
      the informational orthogonality. In addition, pattern descriptors were used to
      qualitatively describe the 2-D peak distribution. With the solutes tested,
      informational orthogonality, zero informational similarity, was observed with
      MECC-SDS/SFC-C1, MECC-SDS/SFC-Carbowax, MECC-TTAB/SFC-Carbowax, HPLC-C18/GLC-DB
      5, HPLC-PBD/SFC-phenyl, SFC-Carbowax/GLC-DB5, and HPLC-phenyl/SFC-phenyl 2-D
      chromatographic systems. Conversely, with the solutes tested, informational
      nonorthogonal behavior described by range-scaled retention time plots to moderate
      to severe band overlap and data clustering was observed with 2-D chromatographic
      systems with high informational similarity and moderate to high degrees of
      synentropy. These results should prove useful for predicting complementary 2-D
      techniques as well as for choosing a second separation technique for confirmation
      of separation or peak purity.

PMID- 8999743
TI  - ["Beret" flap and other flaps in the reconstruction of cancer related loss of
      substance of the ear].
AB  - Major tissue loss involving the ears and periauricular area due to carcinologic
      exeresis is an important problem in reconstructive surgery. We present the
      "beret" flap, a frontal flap with an occipital pedicle, emphasizing the
      simplicity of the procedure and its reliability. We present our personal
      experience and data in the literature and recall the main clinical and
      histological features of these tumors as well as the clinical course and
      treatment.

PMID- 8999744
TI  - [Reoperation and recurrence of pleomorphic adenoma of the parotid. A propos of 62
      cases].
AB  - Between 1967 and 1994, 344 patients were treated with total conservative
      parotidectomy for benign pleomorphic adenoma of the parotid gland. Our
      retrospective study focuses on a sixty-two patients group treated for recurrence
      after biopsy, enucleation or total parotidectomy. Twenty-two patients underwent a
      systematic total parotidectomy after biopsy (n = 7) or enucleation (n = 15).
      Twenty-nine patients were treated with total parotidectomy for local recurrence
      after enucleation. The mean time before this treatment was 8 years-9 months. In
      the third group, 11 patients, (7 patients from our institution), were surgically
      treated for recurrence after total parotidectomy. After enucleation, the
      recurrence rate was high and insufficient margins were found in 27% of the cases.
      In this group, a multicentric recurrence was found in 45% of the cases. In our
      own experience, recurrence after total parotidectomy was noted in 2.4%. The
      surgical salvage was performed with enucleation after identification of the
      branches of the facial nerve. The operative microscope was usefull. In 1 case, a
      second recurrence occured, and in 1 case iterative recurrence was noted. The
      local control rate after total parotidectomy was 99.6% (292/293). Total
      conservative parotidectomy is, for us, the treatment of choice for pleomorphic
      adenoma of the parotid gland.

PMID- 8999745
TI  - [Contribution and limits of acoustic analysis of the voice and alaryngeal speech
      with a computerized system].
AB  - Through a review of published acoustical analyses of alaryngeal voice and speech,
      our aim was to establish the interest and the limitations of a computerized
      acoustical system. One case of esophageal voice and one case of tracheoesophageal
      voice were analysed with the Kay Elemetrics Multidimensional Voice Program for
      voice and Computerised Speech Lab for speech. All the acoustical parameters are
      altered in alaryngeal voice. The automatic calculation of frequential parameters
      are promising but there are errors due to the importance of altered voicing.
      Speech analysis is an important complement to evaluate the phonatory behavior of
      laryngectomized patients.

PMID- 8999746
TI  - Non-Hodgkin's lymphoma of the head and neck in association with HIV infection.
AB  - People infected with HIV have a greater risk of developing malignancies. The most
      frequent one is the Kaposi's sarcoma (KS). The second is the Non-Hodgkin's
      lymphoma (NHL). We report six cases of NHL in association with HIV infection (NHL
      HIV) of the head and neck. Three of them had extranodal location (2 oral
      lymphomas and one case affecting the maxillary sinus). The other 3 cases were
      located in the cervical nodes. The oral malignancies were treated with
      radiotherapy (RT). Chemotherapy was applied to the other 4. Only one of our
      patients has survived more than two years. In one case the NHL was the first
      manifestation of the infection with HIV. Diagnosis of extranodal NHL requires
      search for AIDS.

PMID- 8999747
TI  - [Mode of action and effects of botulinum neurotoxin A].
AB  - Intramuscular injection of botulinum neurotoxin A produces transitory blockade of
      neuromuscular transmission and inhibits presynaptic release of acetylcholine. Its
      action affects peripheral cholinergic receptors, which unlike central receptors,
      can render the toxin active by an internalization mechanism. The intracellular
      target of botulinum neurotoxin A is a protein of the acetylcholine vesicle
      membrane. Currently, indications of botulinum neurotoxin A are reserved solely
      for dystonia. Such treatment has been shown to be effective and tolerance is
      good; histological modifications (muscle atrophy, denervation and axonal sprouts)
      have been observed. The most frequently reported side effects are related to high
      doses and repeated injections of botulinum neurotoxin A.

PMID- 8999748
TI  - [Bone anchored auditory prosthesis. Indications, clinical and audiometric
      results].
AB  - Fourteen patients with conductive or mixed hearing loss were fitted with 16 BAHA.
      Three patients had congenital malformation of the auditory canal. Eleven patients
      had sequelae after bilateral chronic otitis media. All implants were
      osseointegrated. In 81% of the patients, no skin reactions around the abutment
      occured. The subjective evaluation was investigated by means of a questionnaire.
      All patients preferred their BAHA to their previous hearing aid and 93% are
      globally satisfied. Patients were evaluated in sound field, preoperatively and
      postoperatively using warble tones (mean on the average pure tone threshold at
      0.5 1 and 2 kHz of 51.5 dB unaided to 22.6 dB aided with BAHA), speech reception
      threshold (mean of 51.1 dB unaided to 21.9 dB aided with BAHA) and speech
      discrimination. In three cases, we find an "antenna" effect, an improvement in
      reception wearing the Titanium screw and the abutment without the hearing aid
      connected.

PMID- 8999749
TI  - [Paranasal sinus aspergilloma. A propos of 45 cases].
AB  - The authors report a retrospective study of 45 cases of paranasal sinus
      aspergillomas to justify the endonasal endoscopic approach and define its
      limitations. The maxillary form was found in 40 cases (89%). 61% of the patients
      had dental care in the past. Radiographically, calcifications were seen in 43% of
      the cases and heterogenous sinus opacification in 38% of the cases. Mycologic
      study was positive in 94% of the cases. Fungal hyphae were observed in 83% of the
      cases on pathologic examination. During the follow-up, 3 recurrences appeared.
      The following points are emphasized: predictive factors, diagnosis and the
      different surgical procedures and their respective indications.

PMID- 8999750
TI  - [Apropos of 2 cases of mucocele with major ophthalmologic complications treated
      by endoscopic endonasal surgery].
AB  - We report two cases of frontal and ethmoidal mucocele revealed by severe
      ophtalmologic complications and present the clinical data and computed tomography
      and magnetic resonance imaging results together with the treatment. The surgical
      approach and technique are discussed. Recovery of ophtalmologic deficiency was
      excellent.

PMID- 8999751
TI  - [Iatrogenic complications of endonasal surgery].

PMID- 8999752
TI  - Endolymphatic ion concentration in Meniere's disease.

PMID- 8999753
TI  - A story of how terminal illness sometimes can bring out the best in people.

PMID- 8999754
TI  - Impact of changing food choices and eating habits on nutritional status in
      European countries.

PMID- 8999755
TI  - [Actinomycin D resistance of gramicidin-resistant strains of Staphylococcus].
AB  - Factors defining actinomycin D resistance in Staphylococcus aureus resistant to
      gramicidin S were investigated. The results of the thin layer chromatography,
      high-voltage electrophoresis and bioautography showed that the resistant cells
      did not inactivate actinomycin D by the hydrolysis of the lactone bond in the
      antibiotic molecule. The estimation of the cell ability to bind actinomycin D
      revealed that the antibiotic binding to the resistant cells was lower by 70-75
      per cent as compared to the cells of the susceptible strains. Gramicidin S
      impaired the intactness of the cytoplasmic membranes and increased the absorption
      of actinomycin D by the susceptible cells and to a much lesser extent by the
      cells of the resistant strains. Actinomycin D bound by the susceptible cells
      could not be washed out with a buffer solution. It could be separated from the
      cells only by extraction with an organic solvent. Comparative electron microscopy
      of the susceptible and resistant cells demonstrated that the cell walls in the
      resistant strains were 1.5-2-fold thicker than the cell walls in the susceptible
      strains. The actinomycin D resistance of the Staphylococcus strains resistant
      gramicidin S was likely conditioned by the barrier properties of the
      morphologically changed cell walls.

PMID- 8999756
TI  - [Activation of endogenous nucleases as affected by sodium arsenate and
      cisplatin].
AB  - Screening of pharmaceutical agents releasing active nucleases from inactive
      complexes was performed. Cisplatin and sodium arsenate were shown in vitro to
      have such properties. Sodium arsenate which is more expedient for the treatment
      of human patients was studied in vivo. It was administered to albino mice in a
      dose of 0.2 mg/kg once a day for 6 days. Due to the release, the activity of free
      serum DNAse and RNAse markedly increased (1.5-2 times). Activation of endogenic
      nucleases is more promising than the use of exogenic enzymes in complex therapy
      of viral affections and rickettsiosis.

PMID- 8999757
TI  - [Immunomodulating and hepatoprotective action of retinoids in toxic liver
      involvement induced by D-galactosamine].
AB  - The experiments on Wistar rats showed that beta-carotene and retinol acetate
      decreased the level of the biochemical signs of the hepatocyte injury and lowered
      or abolished the immunosuppressive effect induced by D-galactosamine. The
      hepatoprotective and immunomodulating effects of beta-carotene were higher. D
      Galactosamine induced the development of the immunosuppressing properties in
      light erythrocytes and retinol acetate induced the development of the
      immunostimulating properties in heavy erythrocyte of the poisoned animals. beta
      carotene prevented the development of the immunosuppressing properties in such
      cells. The immunomodulating effect of beta-carotene in the toxic affection of the
      liver was associated with blocking or retarding of the entry of the suppressing
      substances to the vascular channel from the hepatocytes and did not depend on
      their action on the erythrocytes.

PMID- 8999758
TI  - [Comparative study of the mechanism of inhibition of Sindbis virus reproduction
      by adamantane derivatives: remantadine and amide of 1-adamantane carboxylic
      acid].
AB  - Amide of 1-adamantane carboxylic acid (AACA), the same as remantadine, was shown
      to have no antiviral action and any influence on the efficiency of the Sindbis
      virus adsorption. However, it significantly inhibited the virus specific
      synthesis of RNA and protein. The main difference between AACA and remantadine
      was in the fact that the efficiency of the inhibition of the Sindbis virus
      reproduction and synthesis of the virus specific RNA in the presence of AACA did
      not markedly decrease even when AACA was added to the experimental system 7 hours
      after the adsorption whereas for the inhibitory effect of remantadine it was to
      be added to the system not later than 2 hours after the adsorption.

PMID- 8999759
TI  - [Antitubercular activity of lomefloxacin in an experiment].
AB  - The effect of lomefloxacin was studied on mice with experimental infection due to
      Mycobacterium tuberculosis. The antibiotic was administered in doses of 100 and
      200 mg/kg. It was shown that the use of lomefloxacin for a month provided a lower
      death rate of the animals with progressing acute generalized tuberculosis, a
      lower level of the lesions in the internal organs and a lower number of the
      Mycobacterium isolates from them. The efficacy of the treatment depended on the
      drug dose. When lomefloxacin was used in a dose of 200 mg/kg, the survival rate
      was much higher and the number of the epithelial unicellular granulomas in the
      tissue of the lung and spleen was markedly decreased while with the lower dose
      the indices did not differ from those in the control.

PMID- 8999762
TI  - [Possible mechanisms of the antimicrobial action of pectin in acute infectious
      diarrhea].

PMID- 8999760
TI  - [Infectious complications in patients in the terminal stages of chronic renal
      insufficiency].
AB  - Characteristics of infectious complications were investigated in 112 patients at
      the terminal stage of renal insufficiency treated by programme hemodialysis. High
      frequency of sepsis (32.4 per cent), urinary tract infections (27.7 per cent),
      respiratory tract infections (26.4 per cent) and tuberculosis (5.6 per cent) was
      stated. The lethal outcomes of the infectious complications averaged 20.3 per
      cent.

PMID- 8999763
TI  - [Maintenance of information in the field of pharmaceutical research: scientific
      bibliographic databases].
AB  - New possibilities for providing studies on pharmaceuticals with the required
      information are discussed. Characteristics of scientific bibliography data bases
      (DB) including large fragments of the information on pharmaceuticals as well as
      those of specific DBs are presented. The peculiarities of the information search
      in every DB and the possible access are discussed. The DBs are accessible via the
      World Net (STN INTERNATIONAL) which gives significant privileges to Russian
      scientists.

PMID- 8999761
TI  - [Synthesis and biological activity of hydrophosphoryl derivatives of amphotericin
      B].
AB  - Reactions of amphotericin B, a polyenic macrolide antibiotic, with aromatic
      aldehydes and H3PO2 resulted in formation of its new hydrophosphoryl derivatives.
      Physico-chemical and biological properties of the compounds were investigated.
      The biological studies showed that the hydrophosphoryl derivatives of
      amphotericin B were low toxic and had antifungal and antiviral activities.

PMID- 8999764
TI  - [Effect of contemporary chemotherapeutic drugs on phagocyte activity and the
      immune response].

PMID- 8999765
TI  - [Ceftriaxone in the treatment of purulent meningitis].

PMID- 8999766
TI  - [Chemical modification of RNAse from Bacillus intermedius. Effect on the
      cytotoxic properties of the enzyme].
AB  - Modified derivatives of RNAse from Bacillus intermedius differing in the
      aggregate enzymatic, physico-chemical and physical properties were prepared. The
      cytotoxic properties of the compounds were tested by the intravital staining of
      FL cells with neutral red. It was shown that the native enzyme cytotoxicity
      correlated with the catalytic activity. However, it was found possible to lower
      the cytotoxicity of the catalytically active compounds by changing the enzyme
      aggregate properties.

PMID- 8999767
TI  - [Immunization with potential Salmonella enteritidis mutants-- 2. Investigations
      on the attenuation and immunogenicity for mice and young hens].
AB  - Adenine-amino acid auxotrophic Salmonella Enteritidis double mutants were
      investigated for their in vivo stability, attenuation und immunogenicity using
      NMRI-mice and SPF-chicks. All mutants used were stable in vivo and attenuated.
      Two mutants were selected for immunization experiments in chickens according to
      their protective ability after a single intraperitoneal immunization in NMRI-mice
      using a homologous and heterologous challenge. After two oral immunizations and
      homologous oral challenge with the S. Enteritidis wild type strain 6403Nalr, a
      significant difference (p < 0.01) was demonstrated between the mean caecal
      bacterial counts of immunized and control chicks. Examination of liver samples
      revealed a significantly lower degree of colonization of internal organs (p <
      0.01) in immunized birds. There was no evidence of cross protection against S.
      Typhimurium using S. Enteritidis mutants.

PMID- 8999768
TI  - [Therapy of liver damage in sheep].
AB  - On the model of fasting metabolism in sheep we examined the effects of
      Prednisolon, Methionin, Heparemin, Glucose 200 and Alwesin: Prednisolon had the
      most lasting antilipolytic and liver protecting (bilirubin decreasing) action.
      Comparatively weaker antilipolytic, antiketogenic and liver protective effects
      were shown by Methionin and Heparemin. Glucose 200 also indicated a similar
      antiketogenic but less antilipolytic influence. The lysin-contained in Heparemin
      obviously displayed no additional effects on the fasting metabolism. During the
      fasting state neither Alwesin, an amino acid mixture, nor Heparemin in CCl4
      intoxicated sheep induced positive pharmacological outcomes. Independent of the
      present investigations, it applies that the regulation of energy, protein and
      electrolyte metabolism is of up most importance in cases of liver damage.

PMID- 8999770
TI  - [Practical experiences in the therapy of postweaning edema disease in piglets].
AB  - In a field trial 23 weeks old weaned piglets were orally inoculated with E. coli
      O139 K12 H1. The piglets received the same food and were kept under the same
      management regime. They were selected randomly into four groups and treated after
      the first clinical signs of CNS involvement of edema disease as follows during
      three days: Group 1: received a single daily i.m. application of 4 mg/kg body
      weight Melperone. Group 2: received a single daily i.m. application of 2 mg/kg
      body weight Amperozide. Group 3: was treated orally (intranasally) with 2 mg/kg
      body weight Amphetamin in a single daily application. Group 4: untreated control.
      The following parameters were evaluated before the begin of the therapy (day 0
      4). A: Occurrence of diarrhea in a group B: Food consumption per piglet per day
      C: Death of piglets per group After the begin of the therapy (day 5-32) D: Death
      of piglets per group E: Average daily feed intake per piglet The results showed
      that the Melperone and Amphetamin treatment was superior regarding all examined
      parameters when compared to Amperozide treatment and to the control group.

PMID- 8999771
TI  - [Dust concentration in deep litter with special reference to activity of growing
      pits and to the use aerosol application].
AB  - Results of continuous measurements of dust during 24 hours on 22 days in one
      round and of behavioural investigations at the same time have shown a high
      correlation of both parameters (dust concentration; locomotoric activity of
      fattening pigs) over a 24 hour-cycle with biphasic dynamics (two phases with
      increased values: after morning feeding between 7 and 9 a.m. and in the afternoon
      between 1 and 3 p.m.). The hour-averages of both variables (n = 528) demonstrated
      a highly significant positive correlation (r = 0.73; p < 0.01); dust
      concentration is increasing with increasing animal activity. It is necessary to
      consider the dynamics of dust values over 24 hours in measuring and evaluating
      concentration or emission of dust under the aspects of animal and environmental
      hygiene. A reduction of dust concentration up to 18% is possible by using an
      aerosol-application of soybean oil-emulgator over 24 hours with an amount of 80
      85 ml per square meter and 24 hr.

PMID- 8999769
TI  - [Effect of acute stress on plasma levels of catecholamines and cortisol in
      addition to metabolites in stress-susceptible growing swine].
AB  - The purpose of this study was to show the behaviour of the plasma level of
      catecholamines in stress-susceptible pigs during an acute stress and to gain new
      insights in the role of catecholamines in the initiation of malignant
      hyperthermia. Therefore, a halothane challenge test was performed in stress
      susceptible growing pigs, and the changes of haematocrit, hormones and
      metabolites were monitored during the handling before the test, during halothane
      exposure and thereafter. Already in connection with the handling before the test,
      haematocrit values and plasma levels of epinephrine, norepinephrine, glucose,
      lactate and potassium increased significantly. However, the plasma concentration
      of cortisol and free glycerol increased gradually and the level of nonesterified
      fatty acids did not show any changes. While the levels of catecholamines and
      potassium decreased already during halothane exposure, haematocrit values and
      concentrations of glucose and lactate continued to increase. The present results
      indicate that the catecholamines are not involved in the initiation of malignant
      hyperthermia.

PMID- 8999772
TI  - [150 years of the Berliner Tierarztliche Gesselschaft. Historical survey].

PMID- 8999773
TI  - [Effect of restraining growth pigs with snare restraints on plasma levels of
      catecholamines, cortisol, insulin and metabolic parameters].
AB  - The aim of the experiments was to evaluate the effect of an acute stressor (snare
      restraint for 5 min) on hormonal and metabolic parameters in pigs and to look for
      parameters which reflect best the stress intensity. The snare restraint resulted
      in an increase in plasma level of epinephrine from 88 +/- 12 to 2264 +/- 470
      pg/ml and in plasma level of norepinephrine from 206 +/- 14 to 7727 +/- 1969
      pg/ml within a minute. In contrast, the cortisol level showed a delayed increase
      from 30.8 +/- 4.9 to 101.8 +/- 12.0 nmol/l. The inhibitory effect of
      catecholamines on insulin secretion resulted in a delayed increase of plasma
      level of insulin from 0.14 +/- 0.01 to 0.29 +/- 0.04 nmol/l. Moreover, there was
      a significant increase in haematocrit and in plasma concentrations of glucose,
      lactate, free glycerol and ascorbic acid. A biphasic pattern in plasma level of
      potassium was observed. The present results suggest that besides the level of
      lactate the plasma concentration of catecholamines reflects best the individual
      degree of excitement and the time of physical strain.

PMID- 8999774
TI  - [Effect of 8-week administration of enalapril plus additional 2-week
      administration of furosemide on heart rate and exocrine pancreas secretion in
      dogs].
AB  - Alteration of pancreatic secretion could be a pathogenetic factor for generation
      of an acute pancreatitis after administration of angiotensin-converting-enzyme
      (ACE) inhibitors. Therefore in 6 conscious dogs (weight 10-12 kg) with chronic
      gastric and duodenal fistulas according to Thomas, we studied single-blind,
      placebo-controlled and randomized the effect of a long-term (74 d) daily oral
      administration of 5 mg of the ACE inhibitor enalapril and of additionally daily
      oral administration of the diuretic furosemide from the 60th day on the secretin-
      (20.5 pmol/kg/h) and caerulein- (7.4, 14.8, 29.6, 59, and 118 pmol/kg/h)
      stimulated pancreatic bicarbonate and protein secretion at day 1, 29, 57, 60, and
      74 after beginning of enalapril administration. Heart rate was measured daily and
      during the experiments. Neither enalapril nor enalapril plus furosemide
      significantly altered heart rate. The hormonally stimulated pancreatic
      bicarbonate secretion was significantly (p < 0.05) increased at day 57, 60, and
      74 by 353%, 397%, and 79%. The hormonally stimulated pancreatic protein secretion
      was also distinctly increased, although not reaching statistical significance.
      The present study shows, that a long-term administration of therapeutic doses of
      enalapril +/-furosemide is capable to enhance the pancreatic bicarbonate
      secretion. Whether this altered pancreatic secretion can be taken for a primary
      origin of the observed cases of acute pancreatitis after therapeutic
      administration of enalapril is uncertain but not refutable.

PMID- 8999775
TI  - [Promotion of wool growth and body weight development of sheep by alimentary
      supplementation with thiocyanate].
AB  - Adult sheep were administered 12 mg thiocyanate (SCN-)/kg body weight orally
      twice a year in altogether 16 respectively 41 single doses under conventional
      keeping during the period of stabling (winter) in two consecutive years.
      Fattening lambs got an analogous SCN- dosage with altogether 4 respectively 34
      single doses under intensive keeping. Aided by this temporarily obtained balance
      of an alimentary SCN- deficiency the following effects were reached during
      conventional keeping: Significant increase of the wool mass in the greasy state
      and a tendency to better breading performance. During intensive fattening an
      increase of the wool mass and of the staple cross-section was proven
      statistically in the mean for all the test animals, but for the increase of the
      staple length it could be shown only by comparison of twins.

PMID- 8999776
TI  - [Utilization of nylon membranes for specific isolation and characterization of
      verotoxin-producing Escherichia coli using DNA probes].
AB  - A method for specific isolation of VT(+)-strains in raw milk is given. DNA
      hybridization technique with DIG-labeled PCR-amplificates as probes are the
      basis. No background is seen by using "DIG Easy Hyb" solution and nylon membranes
      for colony- and plaque-hybridization (Boehringer Mannheim GmbH). Marked colonies
      are visible on the membranes after detection. So it is possible to select these
      colonies from a masterplate. The results are available within one day (without
      enrichment and membrane preparation). After stripping the membranes can be used
      for a new hybridisation to detect another factor of virulence.

PMID- 8999777
TI  - [Helicobacter pylori: antibodies in sera of pigs and calves].
AB  - 64 sera of pigs and 22 sera of calves were investigated in a Helicobacter pylori
      ELISA. The test system was validated with positive and negative reference sera.
      In contrast to other investigations it was tried to exclude false positive
      results by absorbing the sera with Wolinella succinogenes, Campylobacter jejuni
      subsp.jejuni, E. coli and Proteus mirabilis. This proved to be necessary, as the
      extinctions of some sera were reduced considerably. Using this technique sera of
      5 pigs and 6 calves could be identified, which fulfilled the following criteria:
      1. The extinctions were statistically significant above the mean value of the
      corresponding group after absorption with Campylobacter jejuni subsp.jejuni. 2.
      After absorbing the sera of pigs with 3 and the sera of calves with 4 bacteria
      the extinctions were above 50% of that of the human positive serum. 3. The
      extinctions of these sera were-like the positive reference sera-nearly not
      influenced by the absorption. These results indicate the presence of serum
      antibodies in pigs and calves, which react with epitops from Helicobacter pylori.

PMID- 8999778
TI  - [Isolation and experimental transmission of Sarcocystis moulei Neveu-Lemaire,
      1912].
AB  - Of 44 several years old goats slaughtered in Kabul/Afghanistan 16 proved to be
      infected ith Sarcocystis moulei. The large white cysts measuring 2-16 x 1-9 mm
      were found exclusively in oesophageal muscle tissues of the animals. A total of 4
      million sporocysts were harvested from mucosal scrapings of the small intestines
      of two young cats which had been killed 11 or 14 days after being fed with S.
      moulei-containing oesophagi of those goats. For transmission experiments in
      Berlin 11 kids from a S. moulei-free goat breeding as well as 5 Sarcocystis-free
      cats were used. In a preliminary experiment 3 young goats were orally inoculated
      with 200 or 2000 sporocysts from Kabul. In further consecutive trials each of the
      8 remaining kids received 1000 sporocysts, which were isolated from the
      intestines of cats after feeding them S. moulei-cysts from successfully infected
      goats of the first experiment in Berlin. No cysts could be detected in
      oesophageal muscle tissues of two goats which were slaughtered 4 or 6 months
      after sporocyst application. Also no sporocysts were excreted by two cats which
      were fed with the oesophagi of those two animals. In oesophageal muscle tissues
      of the 9 remaining goats, which were slaughtered 19, 25, 43, 44, 59 or 86 months
      after infection, 17 to 140 macroscopically visible cysts of S. moulei were found.
      A definite correlation between age and size of cysts was observed. 19 months p.i.
      cysts measured 1-2 x 0.5-1 mm, at 43 or 44 months p.i. they were already 1-8 x 1
      4 mm, and finally 86 months p.i. they reached a size of 7-13 x 5-8 mm. In H.E.
      stained histological sections cysts appeared to be subdivided into honeycomb like
      chambers by very prominent septae. In smaller cysts all chambers were filled with
      sickle shaped cystozoites, whereas in larger cysts only the chambers at the
      periphery contained cystozoites. Groups of metrocytes were seen within the cyst
      groundsubstance at the periphery of cysts indicating further growth, even of very
      large cysts. Cyst walls measured up to 10 microns in thickness and were composed
      of a primary and a secondary cyst wall. The thin primary cyst wall was folded
      irregularly to give cauliflower like protrusions, which were up to 4.4 microns
      high. The parasitized host cell formed a thick surrounding layer of 6 to 7.5
      microns, which was covered by a 2 to 2.5 microns thick layer of connective
      tissue. All three cats which were fed with S. moulei-cysts in Berlin excreted S.
      moulei-sporocysts with their faeces. Prepatency was 10 days. A total of 100
      sporocysts measured 11.6-13.1 x 8.7-9.4 microns.

PMID- 8999779
TI  - [Sanitation of biowaste compost by using Salmonella enteritidis as a pathogen
      indicator and survival of Salmonella in seepage water].
AB  - The following investigations show the frequency of the occurrence of Salmonella
      in biowastes. Salmonellae, belonging to the serotypes Salmonella enteritidis,
      infantis and agona were detected in 50% of the investigated biowaste samples. In
      order to control the reliability of compositing techniques on eliminating
      pathogens, Salmonella enteritidis was used as a pathogen indicator, which was
      brought into a container composting process and investigated on it's decline.
      Although the input indicator bacteria were eliminated in every case latest until
      the end of container composting, Salmonella was detected in 36% of the
      investigated fresh compost samples. Every time when Salmonella was detected in
      input material, the same serotypes were to be found in seepage water and survived
      there until the end of intensive rot. In laboratory experiments the maximum
      survival time of Salmonella enteritidis in seepage water at +5 degrees C was 42
      days. Seepage water was found out to be a reservoir for survival of Salmonellae
      and has to be considered as a permanent source of contamination. In the question
      of the disposal of seepage water there are disagreements between the instructions
      of TA Siedlungsabfall and TA Luft.

PMID- 8999781
TI  - Striving for atomic resolution in biomolecular topography: the scanning force
      microscope (SFM).
AB  - The invention in 1986 of scanning force microscopy (SFM) provided a new and
      powerful tool for the investigation of biological structures. SFM yields a three
      dimensional view at nanometer resolution of the surface topography associated
      with biological objects. The potential for imaging either macromolecules or
      biomolecules and cells under native (physiological) conditions is currently being
      exploited to obtain functional information at the molecular level. In addition,
      the forces involved in individual bimolecular interactions are being assessed
      under static and dynamic conditions. In this report we focus on the imaging
      capability of the SFM. The rather broad spectrum of applications represented is
      intended to orient the prospective user of biological SFM.

PMID- 8999780
TI  - [Social dominance and rank relationships in domestic pigs: a critical review].
AB  - Viewing dominance as an attribute of repeated agonistic interactions between two
      individuals, the present paper reviews theoretical approaches towards concepts of
      dominance, methods of measurement, and basic principles and problems connected
      with social dominance in domestic pigs. Domestic pigs are able to establish
      social organization structures during all stages of their ontogeny. According to
      definition, dominance relationships occur when a consistent asymmetry of the
      result of dyadic agonistic interactions can be assessed. This must not
      necessarily be connected immediately with a better availability of resources, or
      a high stability of existing dominance relationships, or a functional definition
      of dominance. When sociometric characteristics are calculated, it seems to be
      appropriate to use them for different levels of a biological system (individual,
      individual pair, group). Investigations of social behaviour and dominance in farm
      animals should take into account that mechanisms of social behaviour in confined
      environments are often carried out in parts only. Connections of the dominance
      concept with other concepts of behavioural regulation should be theoretically
      considered and further investigated by experimental studies.

PMID- 8999782
TI  - [Glycoconjugates on the basis of polyacrylamide--tools for studying lectins,
      antibodies, and glycosyltransferases in glycobiology, cytochemistry, and
      histochemistry].
AB  - The synthesis, physicochemical characteristics, and application for studying the
      carbohydrate-binding molecules of some analogues of human cell glycoconjugates,
      neoglycoconjugates, were reviewed. An approach to the synthesis of the
      polyacrylamide derivatives of carbohydrates based on the interaction of fully
      activated polyacrylic acid with omega-aminoalkyl glycosides was described. It
      provides highly reproducible results, is more simple than the previously known
      methods of the synthesis of such derivatives, and expands the range of synthetic
      possibilities because it can provide both the sugar-polymer type molecules and
      conjugates bearing various labels and effectors, sorbents, glycosurfaces, etc. In
      the first part of the review, the synthesis of polyacrylamide conjugates and
      their physicochemical properties were described. In its second part, the
      synthesis of some complex constructions, such as pseudoglycoproteins,
      pseudomucins, glycoparticles, and glycosurfaces, was outlined. Some examples of
      the application of the described conjugates in various fields of glycobiology
      were simultaneously discussed. Prospects of the further development of the
      presented approach in glycotechnology and medicine were also described.

PMID- 8999783
TI  - [Phage mimotopes of monoclonal antibodies against plasma membrane Ca2+-ATPase].
AB  - Libraries of random phage-displayed pentadeca- and hexapeptides were screened
      with the use of four monoclonal antibodies against the human plasma membrane
      Ca2(+)-ATPase. Bacteriophages specifically binding the antibodies were selected,
      and the amino acid sequences of the expressed peptides (mimotopes) were
      determined. Mimotopes for three antibodies (8B8, 2D8, F9) did not correspond to
      the Ca2(+)-ATPase sequence. Pentadecapeptides for the 7C8 antibodies displayed
      similarity to the fragment Glu1097-Arg1113 of the Ca2(+)-ATPase calmodulin
      binding site. However, these antibodies failed to bind recombinant fragment
      Leu1069-Leu1220; therefore, the structure of this epitope remains obscure. This
      work opens a series of studies of the plasma membrane Ca2(+)-ATPase structure by
      means of monoclonal antibodies and the phage display method.

PMID- 8999784
TI  - [Cooperative interaction between protein-porin and lipopolysaccharide].
AB  - The interaction of the pore-forming protein (porin) from the outer membrane of
      Yersinia pseudotuberculosis with the S- and R-forms of lipopolysaccharide (LPS)
      from this bacterium was studied. Analysis of the equilibrium binding of 125I
      labeled S- and R-LPS, as well as the competitive inhibition of this reaction by
      lipid A, core oligosaccharide, and O-specific polysaccharide, suggests that there
      are binding sites on the porin molecule specific to these fragments of the LPS
      molecule. The binding of R-LPS occurs at independent sites of two classes with Ka
      1.7 x 10(5) and 1.1 x 10(5) M-1. S-LPS interacts with porin with positive
      cooperation (h 1.6) and Ka 0.8 x 10(5) M-1. The number of binding sites was found
      to be nine and four R- and S-LPS, respectively. Molecular mechanisms of the
      interaction are discussed.

PMID- 8999785
TI  - [Synthesis and antigenic properties of peptide fragments of beta2-glycoprotein
      I].
AB  - A number of beta 2-glycoprotein-I peptide fragments were synthesized by using the
      Fmoc-scheme of the solid phase method. Antigenic properties of these peptides
      were determined by ELISA. Acm-protected FCKNKEKKCS peptide was shown to inhibit
      binding of anti-cardiolipin antibodies to cardiolipin.

PMID- 8999786
TI  - [A method for obtaining the normalized cDNA libraries based on the effect of
      suppression of polymerase chain reaction].
AB  - A new efficient method for obtaining cDNA libraries with equal representation of
      all cDNA types (equalized libraries) in a single round of equalization was
      developed. The method is based on differences in the renaturation kinetics of
      double-stranded cDNAs of different genes and allow the selection of the equalized
      single-stranded fraction resulted from the incomplete reassociation of the total
      cDNA without laborious and inefficient physical separation. The equalized single
      stranded fractions are selectively amplified by polymerase chain reaction (PCR).
      The amplification of other DNA molecules is inhibited due to PCR suppression,
      i.e. the suppression of amplification of the DNA molecules flanked with long
      interval terminal repeats in PCR with a primer corresponding to the external
      moiety of the repeat. The efficiency of the developed method was estimated in
      obtaining an equalized cDNA library based on mRNA from the activated human T
      lymphocyte Jurkat cell line.

PMID- 8999787
TI  - [Synthesis and properties of mixed ribodeoxyribooligonucleotide duplexes
      containing an internucleotide trisubstituted pyrophosphate bond].
AB  - Fragments of double-stranded RNAs and mixed double-stranded
      ribo/deoxyribooligonucleotides containing an internucleotide trisubstituted
      pyrophosphate bond in a predetermined position of the sugar-phosphate backbone
      were synthesized. The modified internucleotide bond was created between synthetic
      oligonucleotides by chemical ligation with carbodiimide. The chemical ligation
      conditions were optimized for a series of duplexes that differed in the content
      and mutual arrangement of ribo- and deoxyribonucleotide blocks. The yield of
      oligonucleotides containing the trisubstituted internucleotide pyrophosphate bond
      was 90% in an all-deoxy duplex and 15-68% in ribooligonucleotide-containing
      duplexes. The modified duplexes thus obtained are relatively stable in an aqueous
      solution at pH 5.5-7.5, whereas the modified internucleotide bond is cleaved by
      amines to form phosphamide derivatives of the corresponding oligonucleotides.
      Automated solid-phase synthesis of oligonucleotide 3'-ethylphosphates is
      described.

PMID- 8999788
TI  - [Metabolism of 3beta-(2-hydroxyethoxy)cholest-5-ene after intravenous
      administration to rats].
AB  - The intravenous injection of 3 beta-(2-hydroxy-2-[3H]ethoxy)cholest- 5-ene into
      rats with the cannulated common bile duct resulted in the primary accumulation of
      radioactivity in liver (24%) and spleen (12%) tissues, bile (7%), and blood serum
      (15%) after 3 hours. The distribution of 3 beta-(2-hydroxy-2-[3H]ethoxy)cholest-5
      ene throughout various tissues was close to that of [14C]cholesterol being
      administrated under the same conditions. The analysis of radioactive products
      from blood serum showed that 40-60% of 3 beta-(2-hydroxy-2-[3H]ethoxy)- cholest-5
      ene was converted to the acyl derivative under experimental conditions.

PMID- 8999789
TI  - Modeling the Exchanges of Energy, Water, and Carbon Between Continents and the
      Atmosphere
AB  - Atmospheric general circulation models used for climate simulation and weather
      forecasting require the fluxes of radiation, heat, water vapor, and momentum
      across the land-atmosphere interface to be specified. These fluxes are calculated
      by submodels called land surface parameterizations. Over the last 20 years, these
      parameterizations have evolved from simple, unrealistic schemes into credible
      representations of the global soil-vegetation-atmosphere transfer system as
      advances in plant physiological and hydrological research, advances in satellite
      data interpretation, and the results of large-scale field experiments have been
      exploited. Some modern schemes incorporate biogeochemical and ecological
      knowledge and, when coupled with advanced climate and ocean models, will be
      capable of modeling the biological and physical responses of the Earth system to
      global change, for example, increasing atmospheric carbon dioxide.

PMID- 8999790
TI  - The Breakdown of Olivine to Perovskite and Magnesiowustite
AB  - San Carlos olivine crystals under laboratory conditions of 26 gigapascals and 973
      to 1473 kelvin (conditions typical of subducted slabs at a depth of 720
      kilometers) for periods of a few minutes to 19 hours transformed to the phase
      assemblage of perovskite and magnesiowustite in two stages: (i) the oxygen
      sublattice transformed into a cubic close-packed lattice, forming a metastable
      spinelloid, and (ii) at higher temperatures or longer run durations, this
      spinelloid broke down to perovskite and magnesiowustite by redistributing silicon
      and magnesium while maintaining the general oxygen framework. The breakdown was
      characterized by a blocking temperature of 1000 kelvin, below which olivine
      remained metastable, and by rapid kinetics once the reaction was activated.

PMID- 8999791
TI  - Transformation in Garnet from Orthorhombic Perovskite to LiNbO3 Phase on Release
      of Pressure
AB  - High-pressure in situ x-ray diffraction and transmission electron microscopy on
      quenched samples show that natural garnet transforms to orthorhombic perovskite
      (and minor coexisting phases) containing increasing amounts of aluminum with
      increasing pressure. This suggests that the perovskite is the dominant host
      mineral for aluminum in Earth's lower mantle. Orthorhombic perovskite is quenched
      from approximately 35 gigapascals but, because of the increased aluminum content,
      transforms to the LiNbO3 structure upon quenching from approximately 60
      gigapascals.

PMID- 8999793
TI  - Detection and Characterization of the Cumulene Carbenes H2C5 and H2C6
AB  - Two cumulene carbenes, H2C5 and H2C6, were detected in a supersonic molecular
      beam by Fourier transform microwave spectroscopy. Their rotational and leading
      centrifugal distortion constants were determined with high accuracy, such that
      the entire radio spectrum can now be calculated. Like the known carbenes H2C3 and
      H2C4, both molecules have singlet electronic ground states and linear carbon
      chain backbones. They can be produced in sufficiently high concentrations in the
      laboratory that their electronic spectra, expected to lie in the visible, should
      be readily detectable by laser spectroscopy. The microwave spectra of other, more
      exotic isomers may be detectable as well.

PMID- 8999792
TI  - An Fe2IVO2 diamond core structure for the key intermediate Q of methane
      monooxygenase.
AB  - A new paradigm for oxygen activation is required for enzymes such as methane
      monooxygenase (MMO), for which catalysis depends on a nonheme diiron center
      instead of the more familiar Fe-porphyrin cofactor. On the basis of precedents
      from synthetic diiron complexes, a high-valent Fe2(micro-O)2 diamond core has
      been proposed as the key oxidizing species for MMO and other nonheme diiron
      enzymes such as ribonucleotide reductase and fatty acid desaturase. The presence
      of a single short Fe-O bond (1.77 angstroms) per Fe atom and an Fe-Fe distance of
      2.46 angstroms in MMO reaction intermediate Q, obtained from extended x-ray
      absorption fine structure and Mossbauer analysis, provides spectroscopic evidence
      that the diiron center in Q has an Fe2IVO2 diamond core.

PMID- 8999794
TI  - Niobium/Uranium Evidence for Early Formation of the Continental Crust
AB  - Niobium/uranium ratios in greenstone-belt basalts and gabbros indicate that parts
      of the Late Archean mantle beneath Western Australia underwent a level of melt
      extraction, resulting in formation of the continental crust, comparable to that
      seen in the present mantle. The implication is either that (i) the amount of
      continental crust that formed before 2.7 x 10(9) years ago was much greater than
      generally thought or (ii) crustal growth occurred by severe depletion of small
      volumes of the mantle rather than by moderate depletion of a large volume of
      mantle.

PMID- 8999796
TI  - A Legume Ethylene-Insensitive Mutant Hyperinfected by Its Rhizobial Symbiont
AB  - Development of the Rhizobium-legume symbiosis is controlled by the host plant,
      although the underlying mechanisms have remained obscure. A mutant in the annual
      legume Medicago truncatula exhibits an increase of more than an order of
      magnitude in the number of persistent rhizobial infections. Physiological and
      genetic analyses indicate that this same mutation confers insensitivity to the
      plant hormone ethylene for multiple aspects of plant development, including
      nodulation. These data support the hypothesis that ethylene is a component of the
      signaling pathway controlling rhizobial infection of legumes.

PMID- 8999795
TI  - Regulation of NF-kappaB by cyclin-dependent kinases associated with the p300
      coactivator.
AB  - The nuclear factor kappaB (NF-kappaB) transcription factor is responsive to
      specific cytokines and stress and is often activated in association with cell
      damage and growth arrest in eukaryotes. NF-kappaB is a heterodimeric protein,
      typically composed of 50- and 65-kilodalton subunits of the Rel family, of which
      RelA(p65) stimulates transcription of diverse genes. Specific cyclin-dependent
      kinases (CDKs) were found to regulate transcriptional activation by NF-kappaB
      through interactions with the coactivator p300. The transcriptional activation
      domain of RelA(p65) interacted with an amino-terminal region of p300 distinct
      from a carboxyl-terminal region of p300 required for binding to the cyclin E-Cdk2
      complex. The CDK inhibitor p21 or a dominant negative Cdk2, which inhibited p300
      associated cyclin E-Cdk2 activity, stimulated kappaB-dependent gene expression,
      which was also enhanced by expression of p300 in the presence of p21. The
      interaction of NF-kappaB and CDKs through the p300 and CBP coactivators provides
      a mechanism for the coordination of transcriptional activation with cell cycle
      progression.

PMID- 8999797
TI  - Measuring serotonin distribution in live cells with three-photon excitation.
AB  - Tryptophan and serotonin were imaged with infrared illumination by three-photon
      excitation (3PE) of their native ultraviolet (UV) fluorescence. This technique,
      established by 3PE cross section measurements of tryptophan and the monoamines
      serotonin and dopamine, circumvents the limitations imposed by photodamage,
      scattering, and indiscriminate background encountered in other UV microscopies.
      Three-dimensionally resolved images are presented along with measurements of the
      serotonin concentration ( approximately 50 mM) and content (up to approximately 5
      x 10(8) molecules) of individual secretory granules.

PMID- 8999798
TI  - Vascular system defects and impaired cell chemokinesis as a result of Galpha13
      deficiency.
AB  - Heterotrimeric GTP-binding proteins (G proteins) participate in cellular
      signaling and regulate a variety of physiological processes. Disruption of the
      gene encoding the G protein subunit alpha13 (Galpha13) in mice impaired the
      ability of endothelial cells to develop into an organized vascular system,
      resulting in intrauterine death. In addition, Galpha13 (-/-) embryonic
      fibroblasts showed greatly impaired migratory responses to thrombin. These
      results demonstrate that Galpha13 participates in the regulation of cell movement
      in response to specific ligands, as well as in developmental angiogenesis.

PMID- 8999799
TI  - DCP-1, a Drosophila cell death protease essential for development.
AB  - Apoptosis, a form of cellular suicide, involves the activation of CED-3-related
      cysteine proteases (caspases). The regulation of caspases by apoptotic signals
      and the precise mechanism by which they kill the cell remain unknown. In
      Drosophila, different death-inducing stimuli induce the expression of the
      apoptotic activator reaper. Cell killing by reaper and two genetically linked
      apoptotic activators, hid and grim, requires caspase activity. A Drosophila
      caspase, named Drosophila caspase-1 (DCP-1), was identified and found to be
      structurally and biochemically similar to Caenorhabditis elegans CED-3. Loss of
      zygotic DCP-1 function in Drosophila caused larval lethality and melanotic
      tumors, showing that this gene is essential for normal development.

PMID- 8999800
TI  - Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte
      function.
AB  - Lymphocyte-specific interferon regulatory factor (LSIRF) (now called IRF4) is a
      transcription factor expressed only in lymphocytes. Mice deficient in IRF4 showed
      normal distribution of B and T lymphocyes at 4 to 5 weeks of age but developed
      progressive generalized lymphadenopathy. IRF4-deficient mice exhibited a profound
      reduction in serum immunoglobulin concentrations and did not mount detectable
      antibody responses. T lymphocyte function was also impaired in vivo; these mice
      could not generate cytotoxic or antitumor responses. Thus, IRF4 is essential for
      the function and homeostasis of both mature B and mature T lymphocytes.

PMID- 8999801
TI  - Still life, a protein in synaptic terminals of Drosophila homologous to GDP-GTP
      exchangers.
AB  - The morphology of axon terminals changes with differentiation into mature
      synapses. A molecule that might regulate this process was identified by a screen
      of Drosophila mutants for abnormal motor activities. The still life (sif) gene
      encodes a protein homologous to guanine nucleotide exchange factors, which
      convert Rho-like guanosine triphosphatases (GTPases) from a guanosine diphosphate
      bound inactive state to a guanosine triphosphate-bound active state. The SIF
      proteins are found adjacent to the plasma membrane of synaptic terminals.
      Expression of a truncated SIF protein resulted in defects in neuronal morphology
      and induced membrane ruffling with altered actin localization in human KB cells.
      Thus, SIF proteins may regulate synaptic differentiation through the organization
      of the actin cytoskeleton by activating Rho-like GTPases.

PMID- 8999802
TI  - Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor
      vasculature.
AB  - Selective occlusion of tumor vasculature was tested as a therapy for solid tumors
      in a mouse model. The formation of blood clots (thrombosis) within the tumor
      vessels was initiated by targeting the cell surface domain of human tissue
      factor, by means of a bispecific antibody, to an experimentally induced marker on
      tumor vascular endothelial cells. This truncated form of tissue factor (tTF) had
      limited ability to initiate thrombosis when free in the circulation, but became
      an effective and selective thrombogen when targeted to tumor endothelial cells.
      Intravenous administration of the antibody-tTF complex to mice with large
      neuroblastomas resulted in complete tumor regressions in 38 percent of the mice.

PMID- 8999803
TI  - Geographic Distribution of Endangered Species in the United States
AB  - Geographic distribution data for endangered species in the United States were
      used to locate "hot spots" of threatened biodiversity. The hot spots for
      different species groups rarely overlap, except where anthropogenic activities
      reduce natural habitat in centers of endemism. Conserving endangered plant
      species maximizes the incidental protection of all other species groups. The
      presence of endangered birds and herptiles, however, provides a more sensitive
      indication of overall endangered biodiversity within any region. The amount of
      land that needs to be managed to protect currently endangered and threatened
      species in the United States is a relatively small proportion of the land mass.

PMID- 8999804
TI  - Translocation inhibitors define specificity of protein kinase C isoenzymes in
      pancreatic beta-cells.
AB  - The protein kinase C (PKC) family consists of 11 isoenzymes. Following
      activation, each isoenzyme translocates and binds to a specific receptor for
      activated C kinase (RACK) (Mochly-Rosen, D. (1995) Science 268, 247-251) that
      provides an anchoring site in close proximity to the isoenzyme's specific
      substrate. Pancreatic islet cells contain at least six PKC isoenzymes (Knutson,
      K. L., and Hoenig, M. (1994) Endocrinology 135, 881-886). Although PKC activation
      enhances insulin release, the specific function of each isoenzyme is unknown.
      Here we show that following stimulation with glucose, alphaPKC and epsilonPKC
      translocate to the cell's periphery, while deltaPKC and zetaPKC translocate to
      perinuclear sites. betaC2-4, a peptide derived from the RACK1-binding site in the
      C2 domain of betaPKC, inhibits translocation of alphaPKC and reduces insulin
      response to glucose. Likewise, epsilonV1-2, an epsilonPKC-derived peptide
      containing the site for its specific RACK, inhibits translocation of epsilonPKC
      and reduces insulin response to glucose. Inhibition of islet-glucose metabolism
      with mannoheptulose blocks translocation of both alphaPKC and epsilonPKC and
      diminishes insulin response to glucose while calcium-free buffer inhibits
      translocation of alphaPKC but not epsilonPKC and lowers insulin response by 50%.
      These findings illustrate the unique ability of specific translocation inhibitors
      to elucidate the isoenzyme-specific functions of PKC in complex signal
      transduction pathways.

PMID- 8999805
TI  - Spodoptera frugiperda caspase-1, a novel insect death protease that cleaves the
      nuclear immunophilin FKBP46, is the target of the baculovirus antiapoptotic
      protein p35.
AB  - Employing the degenerate primer-dependent polymerase chain reaction approach used
      recently to clone human Mch2, we have identified and cloned the insect Spodoptera
      frugiperda target of the baculovirus antiapoptotic protein p35. This protein
      named Sf caspase-1 belongs to the family of caspases and is highly related to
      human Mch3 and CPP32 in sequence and specific activity. The proenzyme of Sf
      caspase-1 is 299 amino acids in length and can undergo autocatalytic processing
      in Escherichia coli to an active enzyme heterocomplex. Autoprocessing occurs at
      Asp-28, Asp-184, and Asp-195 to generate the large p19/p18 and small p12
      subunits. Sf caspase-1 is able to induce apoptosis in Sf9 cells and is capable of
      cleaving p35 to similar sized fragments as observed with extracts from p35 null
      mutant baculovirus-infected Sf9 cells. Sf caspase-1 activity is potently
      inhibited by p35, suggesting that it is an important target of this antiapoptotic
      protein. Finally, the Sf9 nuclear immunophilin FKBP46 was identified as a death
      associated substrate for Sf caspase-1.

PMID- 8999806
TI  - Constitutive dephosphorylation and activation of a member of the nuclear factor
      of activated T cells, NF-AT1, in Tax-expressing and type I human T-cell leukemia
      virus-infected human T cells.
AB  - The tax gene product of the type I human T-cell leukemia virus (HTLV-I)
      transactivates interleukin-2 (IL-2) gene through activation of an enhancer termed
      CD28 responsive element (CD28RE). Tax activation of the CD28RE is partially
      mediated by a member of the nuclear factor of activated T cells, NF-AT1. We have
      previously shown that NF-AT1 is constitutively active in Jurkat T cells stably
      transfected with the Tax cDNA, although the underlying molecular mechanism and
      physiological relevance of this finding remain unclear. In this report, we
      demonstrate that the active form of NF-AT1 is also present in the nuclei of HTLV
      I-transformed T cells that express the Tax protein. Interestingly, the
      constitutive activation of NF-AT1 in these T cells is associated with its
      dephosphorylation. Furthermore, the dephosphorylated NF-AT1 can be rapidly
      rephosphorylated when the cells are incubated with cyclosporin A, an
      immunosuppressant inhibiting the serine/threonine phosphatase calcineurin. These
      results suggest that activation of NF-AT1 in Tax-expressing and HTLV-I
      transformed T cells results from its dephosphorylation, which in turn may be due
      to deregulation of calcineurin.

PMID- 8999807
TI  - Evidence for a role of Rho-like GTPases and stress-activated protein kinase/c-Jun
      N-terminal kinase (SAPK/JNK) in transforming growth factor beta-mediated
      signaling.
AB  - Transforming growth factor beta (TGF-beta) is a multifunctional factor that
      induces a wide variety of cellular processes which affect growth and
      differentiation. TGF-beta exerts its effects through a heteromeric complex
      between two transmembrane serine/threonine kinase receptors, the type I and type
      II receptors. However, the intracellular signaling pathways through which TGF
      beta receptors act to generate cellular responses remain largely undefined. Here,
      we report that TGF-beta initiates a signaling cascade leading to stress-activated
      protein kinase/c-Jun N-terminal kinase (SAPK/JNK) activation. Expression of
      dominant-interfering forms of various components of the SAPK/JNK signaling
      pathways including Rho-like GTPases, mitogen-activated protein kinase (MAPK)
      kinase kinase 1 (MEKK1), MAPK kinase 4 (MKK4), SAPK/JNK, and c-Jun abolishes TGF
      beta-mediated signaling. Therefore, the SAPK/JNK activation contributes to TGF
      beta signaling.

PMID- 8999808
TI  - Reactive nitrogen intermediates promote low density lipoprotein oxidation in
      human atherosclerotic intima.
AB  - Oxidized low density lipoprotein (LDL) may be of central importance in triggering
      atherosclerosis. One potential pathway involves the production of nitric oxide
      (NO) by vascular wall endothelial cells and macrophages. NO reacts with
      superoxide to form peroxynitrite (ONOO-), a potent agent of LDL oxidation in
      vitro. ONOO- nitrates the aromatic ring of free tyrosine to produce 3
      nitrotyrosine, a stable product. To explore the role of reactive nitrogen species
      such as ONOO- in the pathogenesis of vascular disease, we developed a highly
      sensitive and specific method involving gas chromatography and mass spectrometry
      to quantify 3-nitrotyrosine levels in proteins. In vitro studies demonstrated
      that 3-nitrotyrosine was a highly specific marker for LDL oxidized by ONOO-. LDL
      isolated from the plasma of healthy subjects had very low levels of 3
      nitrotyrosine (9 +/- 7 micromol/mol of tyrosine). In striking contrast, LDL
      isolated from aortic atherosclerotic intima had 90-fold higher levels (840 +/-
      140 micromol/mol of tyrosine). These observations strongly support the hypothesis
      that reactive nitrogen species such as ONOO- form in the human artery wall and
      provide direct evidence for a specific reaction pathway that promotes LDL
      oxidation in vivo. The detection of 3-nitrotyrosine in LDL isolated from vascular
      lesions raises the possibility that NO, by virtue of its ability to form reactive
      nitrogen intermediates, may promote atherogenesis, counteracting the well
      established anti-atherogenic effects of NO.

PMID- 8999809
TI  - Molecular basis of the catalytic differences among DT-diaphorase of human, rat,
      and mouse.
AB  - DT-diaphorase (EC 1.6.99.2), also referred to as NAD(P)H:(quinone-acceptor)
      oxidoreductase, is involved in the reductive activation process of several
      cytotoxic antitumor quinones and nitrobenzenes. It has been observed in our and
      other laboratories that the rat enzyme is significantly more effective in
      activating these drugs than the human and mouse enzymes. These results indicate
      that the available cytotoxic drugs are better substrates for the rat enzyme and
      are not the most ideal prodrugs for activation by DT-diaphorase in human tumors.
      In this study, using site-directed mutagenesis to replace residues in the rat
      enzyme with the human sequences and residues in the human enzyme with the rat
      sequences, we have found that residue 104 (Tyr in the rat enzyme and Gln in the
      human and mouse enzymes) is an important residue responsible for the catalytic
      differences between the rat and the human (and mouse) enzymes. With an exchange
      of a single amino acid, the rat mutant Y104Q behaved like the wild-type human
      enzyme, and the human mutant Q104Y behaved like the wild-type rat enzyme in their
      ability to reductively activate the cytotoxic drug CB 1954 (5-(aziridin-1-yl)-2,4
      dinitrobenzamide). The study also confirms the conclusion of the x-ray structural
      analysis of rat enzyme that residue 130 (Thr in the rat enzyme and Ala in the
      human and mouse enzymes) is positioned near the binding region of the
      nicotinamide portion of NAD(P)H. This structural information is very important
      for designing suitable drugs and approaches for human cancer chemotherapy
      mediated by DT-diaphorase.

PMID- 8999810
TI  - Characterization of the bacterial sensor protein PhoQ. Evidence for distinct
      binding sites for Mg2+ and Ca2+.
AB  - The PhoP/PhoQ two-component regulatory system governs several virulence
      properties in the Gram-negative bacterium Salmonella typhimurium. The PhoQ
      protein is a Mg2+ and Ca2+ sensor that modulates transcription of PhoP-regulated
      genes in response to the extracellular concentrations of these divalent cations.
      We have purified a 146-amino acid polypeptide corresponding to the periplasmic
      (i.e. sensing) domain of the PhoQ protein. Mg2+ altered the tryptophan intrinsic
      fluorescence of this polypeptide whereas Ba2+, which is unable to modulate
      transcription of PhoP-regulated genes, did not. Mg2+ was more effective than Ca2+
      at repressing transcription of PhoP-activated genes in vivo. However, maximal
      repression was achieved when both cations were present. An avirulent mutant
      harboring a single amino acid substitution in the sensing domain of PhoQ
      exhibited lower affinity for Ca2+ but similar affinity for Mg2+. Cumulatively,
      these experiments demonstrate that Mg2+ can bind to the sensing domain of PhoQ
      and establish the presence of distinct binding sites for Mg2+ and Ca2+ in the
      PhoQ protein.

PMID- 8999811
TI  - Cooperative binding of Ca2+ to human interstitial collagenase assessed by
      circular dichroism, fluorescence, and catalytic activity.
AB  - Dissociation of Ca2+ from human interstitial collagenase induced either by
      chelation with EGTA or by dilution resulted in loss of enzyme activity, a red
      shifted emission maximum from 334 to 340 nm and quenching of protein fluorescence
      by 10% at 340 nm. Circular dichroism indicated that secondary structure was
      unaffected by EGTA. Ca2+ binding to the EGTA-treated enzyme as assessed by
      fluorescence was cooperative (Hill coefficient, 2.9; 50% saturation at 0.4 mM
      Ca2+). The dependence of catalytic activity on [Ca2+] was also cooperative (Hill
      coefficient, 1.7-2.0; midpoint [Ca2+], 0.2 mM). The Ca2+-reconstituted protein
      was indistinguishable from the untreated enzyme by activity and fluorescence
      measurements. These results demonstrate that removal of Ca2+ from full-length
      collagenase generates a catalytically incompetent, partially unfolded state with
      native secondary structure but altered tertiary structure characterized by
      exposure of at least one tryptophyl residue to a more polar environment.

PMID- 8999812
TI  - Modeling ligand-gated receptor activity. FhuA-mediated ferrichrome efflux from
      lipid vesicles triggered by phage T5.
AB  - An in vitro assay of iron-ferrichrome translocation across the FhuA protein of
      outer membranes from Escherichia coli has been devised. Upon reconstitution into
      large lipid vesicles, bacteriophage T5 binds to this polyvalent receptor,
      triggering a conformational change that resulted in channel opening. This
      facilitates the translocation of an iron(III)-siderophore, without the
      complexities involved in the in vivo process. Efflux of 55Fe(III)-ferrichrome
      across FhuA channels was determined quantitatively by monitoring the release of
      trapped radioactivity. The assay is rapid, reliable, and specific, because other
      bacteriophages, such as Phi80, fail to trigger channel opening of the FhuA
      receptor.

PMID- 8999814
TI  - Tissue-specific inhibition of apolipoprotein B mRNA editing in the liver by
      adenovirus-mediated transfer of a dominant negative mutant APOBEC-1 leads to
      increased low density lipoprotein in mice.
AB  - APOBEC-1 is a catalytic subunit of an apolipoprotein B (apoB) mRNA editing enzyme
      complex. In humans it is expressed only in the intestine, whereas in mice it is
      expressed in both the liver and intestine. APOBEC-1 exists as a spontaneous
      homodimer (Lau, P. P., Zhu, H.-J., Baldini, A., Charnsangavej, C., and Chan, L.
      (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 8522-8526). We tested the editing
      activity and dimerization potential of three different mouse APOBEC-1 mutants
      using in vitro editing activity assay and immunoprecipitation in the presence of
      epitope-tagged APOBEC-1. One catalytically inactive mutant, mu1 (H61K/C93S/C96S),
      that retains its capacity to dimerize with wild-type APOBEC-1 was found to
      inhibit the editing activity of the latter and was thus a dominant negative
      mutant. Two other inactive mutants that dimerized poorly with APOBEC-1 failed to
      inhibit its activity. Intravenous injection of a mu1 adenovirus, Admu1, in
      C57BL/6J mice in vivo resulted in liver-specific expression of mu1 mRNA. On days
      4 and 9 after virus injection, endogenous hepatic apoB mRNA editing was 23.3 +/-
      5.0 and 36.8 +/- 5.7%, respectively, compared with 65.3 +/- 11 and 71.3 +/- 5.2%,
      respectively, for luciferase adenovirus-treated animals. Plasma apoB-100
      accounted for 95 and 93% of total plasma apoB in Admu1 animals on days 4 and 9,
      respectively, compared with 78 and 72% in luciferase adenovirus animals. Plasma
      cholesterol on day 9 was 98 +/- 17 mg/dl in the mu1-treated animals,
      substantially higher than phosphate-buffered saline-treated (57 +/- 9 mg/dl) or
      luciferase-treated (71 +/- 12 mg/dl) controls. Fast protein liquid chromatography
      analysis of mouse plasma showed that the intermediate density/low density
      lipoprotein fractions in the animals treated with the dominant negative mutant
      adenovirus were much higher than those in controls. We conclude that active
      APOBEC-1 functions as a dimer and its activity is inhibited by a dominant
      negative mutant. Furthermore, apoB mRNA editing determines the availability of
      apoB-100, which in turn limits the amount of intermediate density/low density
      lipoprotein that can be formed in mice. Liver-specific inhibition of apoB mRNA
      editing is an important component of any strategy to enhance the value of mice as
      a model for human lipoprotein metabolism.

PMID- 8999813
TI  - Cloning of an Apobec-1-binding protein that also interacts with apolipoprotein B
      mRNA and evidence for its involvement in RNA editing.
AB  - Apolipoprotein (apo)B mRNA editing is mediated by a multiprotein editosome
      complex. Apobec-1 is the catalytic component of this complex, but other proteins
      involved in editing have not been identified. We used the yeast two-hybrid system
      to identify an apobec-1-interacting protein, ABBP-1. ABBP-1 contains 331 amino
      acid residues and is identical to a previously reported human type A/B hnRNP
      except for a 47-residue insertion at its C-terminal region. It contains typical
      RNP motifs at its N-terminal half and glycine-rich motifs in the C-terminal
      region. Northern blot analysis indicates that ABBP-1 mRNA is distributed in
      multiple human tissues. By deletion analysis, we mapped the apobec-1-binding
      region to the glycine-rich domain. ABBP-1 also binds to apoB mRNA transcripts
      around the editing site and can be UV-cross-linked to them in vitro.
      Immnodepletion of ABBP-1 from an active apoB mRNA editing tissue extract inhibits
      its editing activity. Down-regulation of ABBP-1 in an apobec-1-expressing HepG2
      cell line by transfection with an antisense ABBP-1 cDNA construct leads to
      inhibition of endogenous apoB mRNA editing. We conclude that ABBP-1 is an apobec
      1-interacting protein that may play an important role in apoB mRNA editing.

PMID- 8999815
TI  - Efficient hammerhead ribozymes targeted to the polycistronic Sendai virus P/C
      mRNA. Structure-function relationships.
AB  - The Sendai virus polycistronic P/C mRNA encodes the P and C proteins from
      alternate overlapping reading frames. To determine the functions of these
      proteins in virus replication, hammerhead ribozymes were targeted to cleave the
      5'-untranslated region of the P/C mRNA. Both cell-free and intracellular assays
      were employed to determine ribozyme efficacy. To appropriately compare activities
      between cell-free and intracellular assays, identical ribozymes were synthesized
      in vitro as well as expressed in cells. Ribozyme parameters, namely hybridization
      arm length (HAL) and nonhybridizing extraneous sequences (NES), were found to
      have rate-determining properties. In cell-free reactions, ribozymes with 13-mer
      HAL were up to 10-fold more efficient than those with 9-mer HAL. Ribozymes with 9
      mer HAL were relatively ineffective in transfected cells. Minimizing the number
      of NES increased ribozyme efficiency in vitro. However, ribozymes with minimal
      NES were essentially inert intracellularly. The NES at the termini of the most
      effective intracellular ribozyme, Rz13st ( approximately 95% inhibition of the p
      gene expression), were predicted to fold into stem-loop structures. These
      structures most likely increase ribozyme stability as evidenced by the 8-fold
      higher resistance to ribonuclease T2 digestion of Rz13st compared with Rz13B. Our
      results suggest that when designing effective intracellular ribozymes, parameters
      that enhance formation of productive ribozyme:substrate duplexes and that
      increase RNA stability should be optimized.

PMID- 8999816
TI  - Roles of DNA topoisomerases in the regulation of R-loop formation in vitro.
AB  - We have recently found that stable R-loop formation occurs in vivo and in vitro
      when a portion of the Escherichia coli rrnB operon is transcribed preferentially
      in its physiological orientation. Our results also suggested that the formation
      of such structures was more frequent in topA mutants and was sensitive to the
      template DNA supercoiling level. In the present report we investigated in greater
      detail the involvement of DNA topoisomerases in this process. By using an in
      vitro transcription system with phage RNA polymerases, we found that
      hypernegative supercoiling of plasmid DNAs in the presence of DNA gyrase is
      totally abolished by RNase H, suggesting that extensive R-looping occurs during
      transcription in the presence of DNA gyrase. When RNase A is present, significant
      hypernegative supercoiling occurs only when the 567-base pair rrnB HindIII
      fragment is transcribed in its physiological orientation. This result suggests
      that more stable R-loops are being produced in this orientation. Our results also
      suggest that DNA gyrase can participate in the process of R-loop elongation. The
      strong transcription-induced relaxing activity of E. coli DNA topoisomerase I is
      shown to efficiently counteract the effect of DNA gyrase and thus inhibit
      extensive R-looping. In addition, we found that an R-looped plasmid DNA is a
      better substrate for relaxation by E. coli DNA topoisomerase I as compared with a
      non-R-looped substrate.

PMID- 8999817
TI  - A murine interleukin-4 antagonistic mutant protein completely inhibits
      interleukin-4-induced cell proliferation, differentiation, and signal
      transduction.
AB  - We characterize here a highly efficient antagonist for interleukin-4 (IL-4) in
      the mouse system. In this double mutant of the murine IL-4 protein, both
      glutamine 116 and tyrosine 119 were substituted by aspartic acid residues. This
      variant (QY) bound with similar affinity to the IL-4 receptor alpha subunit as
      wild type IL-4 without inducing cellular responses. In contrast, QY completely
      inhibited in a dose-dependent manner the IL-4-induced proliferation of
      lipopolysaccharide-stimulated murine splenic B-cells, of the murine T cell line
      CTLL-2, and of the murine pre-B-cell line BA/F3. QY also inhibited the IL-4
      stimulated up-regulation of CD23 expression by lipopolysaccharide-stimulated
      murine splenic B-cells and abolished tyrosine phosphorylation of the
      transcription factor Stat6 and the tyrosine kinase Jak3 in IL-4-stimulated BA/F3
      cells. Selective inhibition of IL-4 may be beneficial in T-helper cell type 2
      dominated diseases, like type I hypersensitivity reactions or helminthic
      infections. The QY mutant could be an attractive tool to study in vivo the
      therapeutic potential of IL-4 antagonists in mouse systems.

PMID- 8999818
TI  - Heparin and heparan sulfate bind to snake cardiotoxin. Sulfated oligosaccharides
      as a potential target for cardiotoxin action.
AB  - Cardiotoxins (CTXs) from cobra venom show cytotoxicity toward several cell types.
      They cause systolic heart arrest and severe tissue necrosis. Their interaction
      with phospholipids is established but by itself fails to explain the specificity
      of these toxins; other component(s) of membrane must, therefore, intervene to
      direct them toward their target. We herein show, for the first time, that
      sulfated glycosaminoglycans, heparin, heparan sulfate (HS), chondroitin sulfate
      (CS), and dermatan sulfate (DS), interact with CTX A3, a major component of
      Taiwan cobra venom, by use of affinity chromatography, circular dichroism,
      absorbance, and fluorescence intensity and anisotropy measurements. The relative
      strength of binding, determined by the NaCl concentration required to dissociate
      the CTX-glycosaminoglycan complex, varied as follows: heparin > DS > CS > HS. In
      physiological buffer (8 mM Na2HPO4, 2.7 mM KCl, 1.8 mM KH2PO4, 138 mM NaCl, pH
      7.4), however, only heparin and HS bound to CTX, with respective dissociation
      constants of 1.4 and 16 microM, while CS and DS failed to exhibit well defined
      binding behavior, as indicated by fluorescence measurements. We estimate that CTX
      makes 3-4 ionic contacts with heparin based on a salt-dependent binding study and
      that approximately 40% of binding free energy is derived from purely
      electrostatic interactions under physiological conditions. Sulfated
      pentasaccharide may be sufficient to bind to CTX. We also found that heparin
      accentuates the penetration of CTX into phospholipid membranes as analyzed by
      Langmuir monolayer measurement. In view of these results we propose that heparin
      like moieties of the cell surface may modulate the action of CTX.

PMID- 8999819
TI  - Nonphosphorylatable tyrosine surrogates. Implications for protein kinase
      inhibitor design.
AB  - Tyrosine-specific protein kinases are known to utilize short synthetic tyrosine
      containing peptides as substrates and, as a consequence, a number of inhibitory
      peptides have been prepared by replacing the tyrosine moiety in these peptides
      with a nonphosphorylatable phenylalanine residue. Unfortunately, the inhibitory
      efficacy of these phenylalanine-based peptides is often disappointing. These
      results demonstrate the need for nonphosphorylatable tyrosine surrogates that
      enhance enzyme affinity. As a consequence, we prepared nearly two dozen different
      phenethylamine derivatives, attached them to the C terminus of an active site
      directed peptide (Glu-Glu-Leu-Leu), and examined their effectiveness as
      inhibitors of pp60(c-)src. Three derivatives exhibit enhanced inhibitory activity
      (relative to phenethylamine), including para-substituted sulfonamide and
      guanidino analogs as well as a pentafluoro-containing species. The para
      sulfonamide derivative was selected for further study and was found to function
      as a competitive inhibitor versus variable peptide substrate and as a
      noncompetitive inhibitor versus variable ATP. In short, the enhanced inhibitory
      activity of the sulfonamide derivative is not due to the association of this
      moiety with the ATP binding site. Furthermore, peptides containing the para
      guanidino and pentafluoro derivatives of phenylalanine were prepared. These
      species also display enhanced inhibitory activity toward pp60(c-)src relative to
      the corresponding phenylalanine-based peptide.

PMID- 8999820
TI  - Mutations of Ros differentially effecting signal transduction pathways leading to
      cell growth versus transformation.
AB  - The signaling functions of the oncogenic protein-tyrosine kinase v-Ros were
      studied by systematically mutating the tyrosine residues in its cytoplasmic
      domain. The carboxyl mutation of Tyr-564 produces the most pronounced inhibitory
      effect on v-Ros autophosphorylation and interaction with phospholipase Cgamma. A
      cluster of 3 tyrosine residues, Tyr-414, Tyr-418, and Tyr-419, within the PTK
      domain of v-Ros plays an important role in modulating its kinase activity. The
      mutant F419 and the mutant DI, deleting 6-amino acids near the catalytic loop,
      retain wild type protein tyrosine kinase and mitogenic activities, but have
      dramatically reduced oncogenicity. Both mutant proteins are able to phosphorylate
      or activate components in the Ras/microtubule-associated protein kinase signaling
      pathway. However, F419 mutant protein is unable to phosphorylate insulin receptor
      substrate 1 (IRS-1) or promote association of IRS-1 with phosphatidylinositol 3
      kinase. This tyrosine residue in the context of the NDYY motif may define a novel
      recognition site for IRS-1. Both F419 and DI mutants display impaired ability to
      induce tyrosine phosphorylation of a series of cytoskeletal and cell-cell
      interacting proteins. Thus the F419 and DI mutations define v-Ros sequences
      important for cytoskeleton signaling, the impairment of which correlates with the
      reduced cell transforming ability.

PMID- 8999821
TI  - Synergistic binding of nucleotides and inhibitors to cAMP-dependent protein
      kinase examined by acrylodan fluorescence spectroscopy.
AB  - We have engineered an acrylodan-modified derivative of the catalytic subunit of
      cyclic AMP-dependent protein kinase (cAPK) whose fluorescence emission signal has
      allowed the synergistic binding between nucleotides and physiological inhibitors
      of cAPK to be examined (Whitehouse, S., and Walsh, D. A. (1983) J. Biol. Chem.
      258, 3682-3692). In the presence of the regulatory subunit, RI, the affinity of
      cAPK for adenosine, ADP, AMPPNP (adenosine 5'-(beta, gamma-imino)triphosphate),
      or ATP was 5-, 50-, 120-, and 15,000-fold enhanced, while in the presence of the
      heat-stable inhibitor protein of cAPK (PKI), there was a 3-, 20-, 33-, and 2000
      fold enhancement in the binding of these nucleotides, respectively. A short
      inhibitor peptide, PKI-(14-22), enhanced the binding of ADP to the same degree as
      did full-length PKI (20-fold) but, in contrast, did not significantly enhance the
      binding of ATP or AMPPNP. The full binding synergism between PKI and either ATP
      (2000-fold) or AMPPNP (33-fold) to cAPK could, however, be mimicked by a longer
      peptide, PKI-(5-24), suggesting that the PKI NH2 terminus (residues 5-13) is most
      likely critical. Since this region is remote from the ATP gamma-phosphate, the
      binding synergism must arise through an extended network communication mechanism
      between the PKI NH2 terminus and the ATP binding site.

PMID- 8999822
TI  - Fungal galectins, sequence and specificity of two isolectins from Coprinus
      cinereus.
AB  - Galectins are members of a genetically related family of beta-galactoside-binding
      lectins. At least eight distinct mammalian galectins have been identified. More
      distantly related, but still conserving amino acid residues critical for
      carbohydrate-binding, are galectins in chicken, eel, frog, nematode, and sponge.
      Here we report that galectins are also expressed in a species of fungus, the inky
      cap mushroom, Coprinus cinereus. Two dimeric galectins are expressed during
      fruiting body formation which are 83% identical to each other in amino acid
      sequence and conserve all key residues shared by members of the galectin family.
      Unlike most galectins, these have no N-terminal post-translational modification
      and no cysteine residues. We expressed one of these as a recombinant protein and
      studied its carbohydrate-binding specificity using a novel nonradioactive assay.
      Binding specificity has been well studied for a number of other galectins, and
      like many of these, the recombinant C. cinereus galectin shows particular
      affinity for blood group A structures. These results demonstrate not only that
      the galectin gene family is evolutionarily much older than previously realized
      but also that fine specificity for complex saccharide structures has been
      conserved. Such conservation implies that galectins evolved to perform very basic
      cellular functions, presumably by interaction with glycoconjugates bearing
      complex lactoside carbohydrates resembling blood group A.

PMID- 8999823
TI  - Depletion of intracellular calcium stores activates smooth muscle cell calcium
      independent phospholipase A2. A novel mechanism underlying arachidonic acid
      mobilization.
AB  - Herein we present multiple lines of evidence which demonstrate that depletion of
      internal calcium stores is both necessary and sufficient for the activation of
      calcium-independent phospholipase A2 during arginine vasopressin (AVP)-mediated
      mobilization of arachidonic acid in A-10 smooth muscle cells. First, AVP-induced
      [3H]arachidonic acid release was independent of increases in cytosolic calcium
      yet was decreased by pharmacological inhibition of the release of calcium ion
      from internal stores. Second, thapsigargin induced the dramatic release of
      [3H]arachidonic acid from A-10 cells at a similar rate as the AVP-induced release
      of arachidonic acid, and the release of arachidonic acid by either AVP or
      thapsigargin was entirely inhibited by (E)-6-(bromomethylene)-3-(1-naphthalenyl)
      2H-tetrahydropyran-2-one (BEL). Third, the magnitude of thapsigargin-induced
      [3H]arachidonic acid release was entirely independent of alterations in cytosolic
      calcium concentration. Fourth, A23187 resulted in the BEL-inhibitable release of
      [3H]arachidonic acid from A-10 cells even when ionophore-induced increases in
      cytosolic calcium were completely prevented by calcium chelators. Fifth,
      pretreatment of A-10 cells with a calmodulin antagonist (N-(6-aminohexyl)-5
      chloro-1-naphthalenesulfonamide, HCl) resulted in the time-dependent decrease of
      subsequent thapsigargin-induced [3H]arachidonic acid release. Collectively, these
      results identify a novel paradigm which links alterations in calcium homeostasis
      to the calmodulin-mediated regulation of calcium-independent phospholipase A2
      through the depletion of internal calcium stores.

PMID- 8999824
TI  - Studies on the site and mechanism of attachment of phosphorylcholine to a
      filarial nematode secreted glycoprotein.
AB  - We have recently shown that the immunomodulatory substance phosphorylcholine (PC)
      is covalently attached to ES-62, a major secreted protein of the filarial
      nematode parasite Acanthocheilonema viteae, via an N-linked glycan. Linkage of PC
      to N-glycans is previously unreported, and hence we have investigated the
      biochemical events underlying it. PC addition was found by pulse-chase
      experiments to be a fairly early event during intracellular transport, occurring
      within 40-60 min of protein synthesis. Biosynthetic labeling/immunoprecipitation
      experiments revealed that addition of PC to ES-62 was blocked by (i) brefeldin A,
      an inhibitor of trafficking of newly synthesized proteins from the endoplasmic
      reticulum (ER) to the Golgi, (ii) 1-deoxynorijirimycin, an inhibitor of
      glucosidase activity in the ER, and (iii) 1-deoxymannojirimycin, an inhibitor of
      mannosidase I in the cis Golgi. Swainsonine, an inhibitor of mannosidase II in
      the medial Golgi, did not affect PC addition. Taken together these data indicate
      that PC attachment is a post-ER event which is dependent on generation of an
      appropriate substrate during oligosaccharide processing. Furthermore, they
      strongly suggest that PC addition takes place in the medial Golgi and that the
      substrate for addition is the 3-linked branch of Man5GlcNAc3 or Man3GLcNAc3.

PMID- 8999825
TI  - Antibiotics induce genome-wide hypermethylation in cultured Nicotiana tabacum
      plants.
AB  - Plant genomic DNA methylation was analyzed by an improved SssI methyltransferase
      assay and by genomic sequencing with sodium bisulfite. Kanamycin, hygromycin, and
      cefotaxime (also called Claforan) are commonly used as selective agents for the
      production of transgenic plants. These antibiotics caused DNA hypermethylation in
      tobacco plants grown in vitro, which was both time- and dose-dependent. An
      exposure of the plantlets to 500 mg/liter cefotaxime for 1 month caused the de
      novo methylation of 3 x 10(7) CpG sites/haploid genome of 3.5 x 10(9) base pairs.
      It occurred in high, moderate, and low repetitive DNA and was not reversible upon
      the removal of the antibiotics. Reversion was only observed in progeny grown in
      the absence of drugs. Analysis of the promoter regions of two single-copy genes,
      an auxin-binding protein gene and the class I chitinase gene, showed the
      hypermethylation to be heterogeneous but biased toward CpGs. The hypermethylation
      of the class I chitinase and the auxin-binding protein promoters was not a
      consequence of a drug-induced gene amplification.

PMID- 8999826
TI  - Structure-function relationships of cellular retinoic acid-binding proteins.
      Quantitative analysis of the ligand binding properties of the wild-type proteins
      and site-directed mutants.
AB  - It has been suggested that electrostatic interactions are critical for binding of
      retinoic acid by cellular retinoic acid-binding proteins (CRABP-I and CRABP-II).
      However, the roles of two conserved arginine residues (Arg-111 and Arg-131 in
      CRABP-I; Arg-111 and Arg-132 in CRABP-II) that interact with the carboxyl group
      of retinoic acid have not been evaluated. A novel competitive binding assay has
      been developed for measuring the relative dissociation constants of the site
      directed mutants of CRABPs. Arg-111 and Arg-132 of CRABP-II were replaced with
      methionine by site-directed mutagenesis. The relative dissociation constants of
      R111M and R132M (Kd (R111M)/Kd (CRABP-II) and Kd (R132M)/Kd(CRABP-II)) were
      determined to be 40-45 and 6-8, respectively. The ring protons of the aromatic
      residues of the wild-type CRABP-II and the two mutants were sequentially assigned
      by two-dimensional homonuclear NMR in conjunction with three-dimensional
      heteronuclear NMR. Detailed analysis of the nuclear Overhauser effect
      spectroscopy spectra of the proteins indicated that the conformations of the two
      mutants are highly similar to that of the wild-type CRABP-II. These results taken
      together showed that Arg-111 and Arg-132 are important for binding retinoic acid
      but contribute to the binding energy only by approximately 2.2 and 1.2 kcal/mol,
      respectively. In addition, the relative dissociation constant of CRABP-II and
      CRABP-I (Kd (CRABP-II)/Kd (CRABP-I)) was determined to be 2-3, in close agreement
      with that calculated using the apparent Kd values determined under the same
      conditions by fluorometric titrations.

PMID- 8999827
TI  - Phosphorylation of serine residues 3, 6, 10, and 13 distinguishes membrane
      anchored from soluble glutamic acid decarboxylase 65 and is restricted to
      glutamic acid decarboxylase 65alpha.
AB  - GAD65, the smaller isoform of the gamma-aminobutyric acid-synthesizing enzyme
      glutamic acid decarboxylase is detected as an alpha/beta doublet of distinct
      mobility on SDS-polyacrylamide gel electrophoresis. Glutamic acid decarboxylase
      (GAD) 65 is reversibly anchored to the membrane of synaptic vesicles in neurons
      and synaptic-like microvesicles in pancreatic beta-cells. Here we demonstrate
      that GAD65alpha but not beta is phosphorylated in vivo and in vitro in several
      cell types. Phosphorylation is not the cause of the alpha/beta heterogeneity but
      represents a unique post-translational modification of GAD65alpha. Two
      dimensional protein analyses identified five phosphorylated species of three
      different charges, which are likely to represent mono-, di-, and
      triphosphorylated GAD65alpha in different combinations of phosphorylated serines.
      Phosphorylation of GAD65alpha was located at serine residues 3, 6, 10, and 13,
      shown to be mediated by a membrane bound kinase, and distinguish the membrane
      anchored, and soluble forms of the enzyme. Phosphorylation status does not affect
      membrane anchoring of GAD65, nor its Km or Vmax for glutamate. The results are
      consistent with a model in which GAD65alpha and -beta constitute the two subunits
      of the native GAD65 dimer, only one of which, alpha, undergoes phosphorylation
      following membrane anchoring, perhaps to regulate specific aspects of GAD65
      function in the synaptic vesicle membrane.

PMID- 8999828
TI  - The role of sphingolipids in the maintenance of fibroblast morphology. The
      inhibition of protrusional activity, cell spreading, and cytokinesis induced by
      fumonisin B1 can be reversed by ganglioside GM3.
AB  - Previous studies demonstrated that inhibition of sphingolipid synthesis by the
      mycotoxin fumonisin B1 (FB1) disrupts axonal growth in cultured hippocampal
      neurons (Harel, R., and Futerman, A. H. (1993) J. Biol. Chem. 268, 14476-14481)
      by affecting the formation or stabilization of axonal branches (Schwarz, A.,
      Rapaport, E., Hirschberg, K., and Futerman, A.H. (1995) J. Biol. Chem. 270, 10990
      10998). We now demonstrate that long term incubation with FB1 affects fibroblast
      morphology and proliferation. Incubation of Swiss 3T3 cells with FB1 resulted in
      a decrease in synthesis of ganglioside GM3, the major glycosphingolipid in 3T3
      fibroblasts and of sphingomyelin. The projected cell area of FB1-treated cells
      was approximately 45% less than control cells. FB1 had no affect on the
      organization of microtubules or intermediate filaments, but fewer actin-rich
      stress fibers were observed, and there was a loss of actin-rich lamellipodia at
      the leading edge. Three other processes involving the actin cytoskeleton,
      cytokinesis, microvilli formation, and the formation of long processes induced by
      protein kinase inhibitors, were all disrupted by FB1. All the effects of FB1 on
      cell morphology could be reversed by addition of ganglioside GM3 even in the
      presence of FB1, whereas the bioactive intermediates, sphinganine, sphingosine,
      and ceramide, were without effect. Finally, FB1 blocked cell proliferation and
      DNA synthesis in a reversible manner, although ganglioside GM3 could not reverse
      the effects of FB1 on cell proliferation. Together, these data suggest that
      ongoing sphingolipid synthesis is required for the assembly of both new membrane
      and of the underlying cytoskeleton.

PMID- 8999829
TI  - A structurally novel transferrin-like protein accumulates in the plasma membrane
      of the unicellular green alga Dunaliella salina grown in high salinities.
AB  - The alga Dunaliella salina is outstanding is its ability to withstand extremely
      high salinities. To uncover mechanisms underlying salt tolerance, a search was
      carried out for salt-induced proteins. The level of a plasma membrane 150-kDa
      protein, p150, was found to increase with rising external salinity (Sadka, A.,
      Himmelhoch, S., and Zamir, A. (1991) Plant Physiol. 95, 822-831). Based on its
      cDNA-deduced sequence, p150 belongs to the transferrin family of proteins so far
      identified only in animals. This, to our best knowledge, is the first
      demonstration of a transferrin-like protein in a photosynthetic organism. Unlike
      animal transferrins, p150 contains three, rather than two, internal repeats and a
      COOH-terminal extension including an acidic amino acid cluster. In intact cells
      p150 is degraded by Pronase, indicating that the protein is extracellularly
      exposed. The relationship of p150 to iron uptake is supported by the induction of
      the protein in iron-deficient media and by its radioactive labeling in cells
      grown with 59Fe. Accumulation of p150 is transcriptionally regulated. It is
      proposed that p150 acts in iron uptake other than by receptor-mediated
      endocytosis and that its induction permits the cells to overcome a possible
      limitation in iron availability under high salinities.

PMID- 8999830
TI  - Probing the hemoglobin central cavity by direct quantification of effector
      binding using fluorescence lifetime methods.
AB  - Time-resolved fluorescence methods have been used to show that 8-hydroxy-1,3,6
      pyrenetrisulfonate (HPT), a fluorescent analog of 2,3-diphosphoglycerate, binds
      to the central cavity of carboxyhemoglobin A (HbACO) at pH 6.35. A direct
      quantitative approach, based on the distinctive free and bound HPT fluorescent
      lifetimes of 5.6 ns and approximately 27 ps, respectively, was developed to
      measure the binding affinity of this probe. HPT binds to a single site and is
      displaced by inositol hexaphosphate at a 1:1 mol ratio, indicating that binding
      occurs at the 2,3-diphosphoglycerate site in the central cavity. Furthermore, the
      results imply that low pH HbACO exists as an altered R state and not an
      equilibrium mixture of R and T states. The probe was also used to monitor
      competitive effector binding and to compare the affinity of the binding site in
      several cross-bridged HbA derivatives.

PMID- 8999831
TI  - Membrane insertion, glycosylation, and oligomerization of inositol trisphosphate
      receptors in a cell-free translation system.
AB  - In order to study the membrane topology, processing, and oligomerization of
      inositol trisphosphate receptor (IP3R) isoforms, we have utilized RNA templates
      encoding putative transmembrane domains to program a cell-free translation system
      of rabbit reticulocyte lysates supplemented with canine pancreas microsomes. In
      the absence of microsomes, translation of the RNA templates encoding all the
      putative transmembrane domains present in the C-terminal segment of the type I
      (1TM) and type III (3TM) IP3R isoforms resulted in a 62- and 59-kDa polypeptide,
      respectively. In both cases, an additional band approximately 3 kDa larger was
      observed upon the addition of microsomes. Both bands in the translation doublet
      were integrated into microsomal membranes and were full-length translation
      products, as shown by sedimentation through a sucrose cushion and
      immunoprecipitation with C-terminal isoform-specific antibodies. With both
      isoforms, N-glycopeptidase F digestion indicates that the upper band in the
      doublet corresponds to a glycosylated translation product. A 17-kDa protected
      fragment was observed after proteinase-K digestion of 1TM translated in the
      presence of microsomes. The pattern and size of protected fragments was
      consistent with the current six-transmembrane domain model of IP3R topology.
      Cotranslation of both 1TM and 3TM RNA templates in the presence of microsomes
      followed by immunoprecipitation with isoform specific antibodies revealed
      coimmunoprecipitation of translation products. This was not observed when the
      isoforms were translated separately and then mixed, suggesting that
      heteroligomerization occurs cotranslationally. A construct encoding only the
      first putative transmembrane domain of the type I isoform was found to be
      sufficient for integration into membranes but was unable to oligomerize with
      either 1TM or 3TM. Cotranslation experiments using additional constructs indicate
      that the major structural determinant for homoligomerization lies between
      putative transmembrane domain 5 and the C terminus. A second oligomerization
      domain involved in stabilization of heteroligomers is present within the first
      four transmembrane domains.

PMID- 8999832
TI  - Aspergillus nidulans stcL encodes a putative cytochrome P-450 monooxygenase
      required for bisfuran desaturation during aflatoxin/sterigmatocystin
      biosynthesis.
AB  - The Aspergillus nidulans stcL gene is predicted to encode a cytochrome P-450
      monooxygenase and is located within a cluster of other genes that are required
      for synthesis of sterigmatocystin. Inactivation of stcL resulted in strains that
      accumulate dihydrosterigmatocystin, a tetrahydrobisfuran containing molecule that
      is very similar to the unsaturated product of the wild-type pathway,
      sterigmatocystin. This observation led us to hypothesize that the A. nidulans
      sterigmatocystin biosynthetic pathway is branched similarly to the aflatoxin
      pathway in Aspergillus parasiticus and Aspergillus flavus and that StcL is
      required for the desaturation of the bisfuran moiety in the
      sterigmatocystin/aflatoxin precursor versicolorin B. This prediction was
      confirmed by feeding the stcL mutant with the subsequent pathway intermediate,
      versicolorin A, which resulted in accumulation of both sterigmatocystin and
      dihydrosterigmatocystin, indicating that StcL functions before versicolorin A
      synthesis. A. nidulans stcU was shown previously to encode a ketoreductase
      required to convert versicolorin A to demethylsterigmatocystin and an stcL, stcU
      double mutant strain was shown here to accumulate only versicolorin B. These
      results indicate that both versicolorin A and versicolorin B can serve as
      substrates for StcU, resulting in a branched pathway. The final product of each
      branch are sterigmatocystin and dihydrosterigmatocystin, respectively.

PMID- 8999833
TI  - Molecular cloning and characterization of Porphyromonas gingivalis lysine
      specific gingipain. A new member of an emerging family of pathogenic bacterial
      cysteine proteinases.
AB  - The proteinases of Porphyromonas gingivalis are key virulence factors in the
      etiology and progression of periodontal disease. Previous work in our
      laboratories resulted in the purification of arginine- and lysine-specific
      cysteine proteinases, designated gingipains, that consist of several tightly
      associated protein subunits. Recent characterization of arginine-specific
      gingipain-1 (gingipain R1; RGP-1) revealed that the sequence is unique and that
      the protein subunits are initially translated as a polyprotein encoding a
      proteinase domain and multiple adhesin domains (Pavloff, N., Potempa, J., Pike,
      R. N., Prochazka, V., Kiefer, M. C., Travis, J., and Barr, P. J. (1995) J. Biol.
      Chem. 270, 1007-1010). We now show that the lysine-specific gingipain (gingipain
      K; KGP) is also biosynthesized as a polyprotein precursor that contains a
      proteinase domain that is 22% homologous to the proteinase domain of RGP-1 and
      multiple adhesin domains. This precursor is similarly processed at distinct sites
      to yield active KGP. The key catalytic residues in the proteinase domain of KGP
      are identical to those found in RGP-1, but there are significant differences
      elsewhere within this domain that likely contribute to the altered substrate
      specificity of KGP. Independent expression of the proteinase domain in insect
      cells has shown that KGP does not require the presence of the adhesin domains for
      correct folding to confer proteolytic activity.

PMID- 8999834
TI  - Altering substrate specificity of Bacillus sp. SAM1606 alpha-glucosidase by
      comparative site-specific mutagenesis.
AB  - The Bacillus sp. SAM1606 alpha-glucosidase with a broad substrate specificity is
      the only known alpha-glucosidase that can hydrolyze alpha,alpha'-trehalose
      efficiently. The enzyme exhibits a very high sequence similarity to the oligo-1,6
      glucosidases (O16G) of Bacillus thermoglucosidasius and Bacillus cereus which
      cannot act on trehalose. These three enzymes share 80% identical residues within
      the conserved regions (CR), which have been suggested to be located near or at
      the active site of the alpha-amylase family enzymes. To identify by site-specific
      mutagenesis the critical residues that determine the broad substrate specificity
      of the SAM1606 enzyme we compared the CR sequences of these three glucosidases
      and selected five targets to be mutagenized in SAM1606 alpha-glucosidase, Met76,
      Arg81, Ala116, Gly273, and Thr342. These residues have been specifically replaced
      by in vitro mutagenesis with Asn, Ser, Val, Pro, and Asn, respectively, as in the
      Bacillus O16G. The 12 mutant enzymes with single and multiple substitutions were
      expressed and characterized kinetically. The results showed that the 5-fold
      mutation virtually abolished the affinity of the enzyme for alpha, alpha'
      trehalose, whereas the specificity constant for the hydrolysis of isomaltose, a
      good substrate for both the SAM1606 enzyme and O16G, remained essentially
      unchanged upon the mutation. This loss in affinity for trehalose was critically
      governed by a Gly273 --> Pro substitution, whose effect was specifically enhanced
      by the Thr342 --> Asn substitution in the 5-fold and quadruple mutants. These
      results provide evidence for the differential roles of the amino acid residues in
      the CR in determining the substrate specificity of the alpha-glucosidase.

PMID- 8999835
TI  - Structural domain organization of gastric H+,K+-ATPase and its rearrangement
      during the catalytic cycle.
AB  - Differential scanning calorimetry has been used to characterize the thermal
      denaturation of gastric (H+,K+)-ATPase. The excess heat capacity function of
      (H+,K+)-ATPase in highly oriented gastric vesicles displays two peaks at 53.9
      degrees C (Tm1) and 61.8 degrees C (Tm2). Its thermal denaturation is an
      irreversible process that does not exhibit kinetic control and can be resolved in
      two independent two-state processes. They can be assigned to two cooperative
      domains located in the cytoplasmic loops of the alpha-subunit, according to the
      disappearance of the endothermic signal upon removal of these regions by
      proteinase K digestion. Analysis of the thermal-induced unfolding of the enzyme
      trapped in different catalytic cycle intermediates has allowed us to get insight
      into the E1-E2 conformational change. In the E1 forms both transitions are always
      observed. As Tm1 is shifted to Tm2 by vanadate and ATP interaction, the unfolding
      mechanism changes from two independent to two sequential two-state transitions,
      revealing interdomain interactions. Stabilization of the E2 forms results in the
      disappearance of the second transition at saturation by K+, Mg2+-ATP, and Mg2+
      vanadate as well as in significant changes in Tm2 and DeltaH1. The catalytic
      domain melts following a process in which intermolecular interactions either in
      the native or in the unfolded state might be involved. Interestingly, the E2
      vanadate-K+ form displays intermediate properties between the E1 and E2
      conformational families.

PMID- 8999836
TI  - Role of Rho family proteins in phospholipase D activation by growth factors.
AB  - Treatment of fibroblasts with growth factors results in activation of
      phospholipase D (PLD). In order to determine the role of the Rho family of small
      GTPases in growth factor-mediated PLD activation, we used cells transfected with
      wild type and mutant Rac1. In response to epidermal growth factor (EGF), PLD
      activity was greatly increased in Rat1 fibroblasts expressing wild type Rac1
      (wtRac1), and completely abrogated in cells expressing dominant negative N17Rac1,
      consistent with Rac1 mediating the action of this growth factor. In contrast, in
      cells treated with platelet-derived growth factor (PDGF) or phorbol ester, the
      wtRac1 cells showed little or no enhancement of PLD activity, and the response
      was not affected in the N17Rac1 cells, implying that Rac1 played a minimal role
      in the activation of PLD by PDGF or protein kinase C. Both growth factors
      produced an attenuated PLD response in cells expressing constitutively active
      V12Rac1, but these cells showed other changes, including altered morphology,
      increased basal PLD, and decreased growth factor receptor autophosphorylation.
      The effects of EGF and PDGF on phosphoinositide phospholipase C activity were not
      enhanced in cells expressing wtRac1 or inhibited in those expressing N17Rac1. In
      cells expressing constitutively active V12Rac1, basal phosphoinositide
      phospholipase C was elevated, but there were no significant effects of EGF or
      PDGF. We used C3 transferase of Clostridium botulinum, which ADP-ribosylates and
      inactivates RhoA, to investigate the involvement of RhoA in the activation of PLD
      by PDGF. Cells expressing wtRac1 and N17Rac1 showed a decreased PLD in response
      to PDGF when treated with C3 transferase, indicating a role for RhoA. In summary,
      these data indicate a major role for Rac1 in the activation of PLD by EGF, but
      not PDGF or protein kinase C.

PMID- 8999837
TI  - Identification of a rat oltipraz-inducible UDP-glucuronosyltransferase (UGT1A7)
      with activity towards benzo(a)pyrene-7,8-dihydrodiol.
AB  - Previous work has shown that polycyclic aromatic hydrocarbons and oltipraz both
      induce an unidentified rat liver UDP-glucuronosyltransferase with activity toward
      benzo(a)pyrene-7, 8-diol, the proximate carcinogenic form of benzo(a)pyrene. Here
      we report the isolation of a benzo(a)pyrene-7,8-diol transferase-encoding cDNA,
      LC14, from an adult rat hepatocyte-derived cell line (RALA255-10G LCS-3). The
      predicted amino acid sequence of LC14 is nearly identical (5 differences out of
      531 residues) to that deduced from UGT1A7, recently cloned at the genomic DNA
      level (Emi, Y., Ikushiro, S., and Kyanagi, T. (1995) J. Biochem. (Tokyo) 117, 392
      399). Northern analysis of RNA from female F344 rat liver and LCS-3 cells
      revealed over a 40-fold and 4.4-fold enhancement by oltipraz treatment,
      respectively. Benzo(a)pyrene-7, 8-diol glucuronidating activity was detected (0.4
      nmol/10(6) cells/16 h) in AHH-1 cells transfected with the LC14 expression
      vector, pMF6-LC14-3. The LC14-encoded transferase exhibited even higher activity
      toward certain benzo(a)pyrene phenols, including the major 3- and 9-phenol
      metabolites (4.1 and 2.8 nmol/10(6) cells/16 h, respectively). The Km of the
      enzyme for (-)-trans benzo(a)pyrene-7, 8-diol and 3-OH-BP was 15.5 and 12.3
      microM, respectively. Northern analyses of total RNA revealed expression of LC14
      or LC14-like RNA in all extrahepatic tissues tested. Marked inducibility by
      oltipraz was observed only in liver and (to a lesser extent) intestine. The
      results suggest that induction of UGT1A7 may explain the increased
      glucuronidating activities toward benzo(a)pyrene-7,8-diol and other metabolites
      that occur following treatment with polycyclic aromatic hydrocarbon-type inducing
      agents and oltipraz. UGT1A7 appears to represent an important cellular
      chemoprotective enzyme which mediates conjugation and elimination of toxic
      benzo(a)pyrene metabolites.

PMID- 8999838
TI  - Regulation of skeletal muscle Ca2+ release channel (ryanodine receptor) by Ca2+
      and monovalent cations and anions.
AB  - The effects of ionic composition and strength on rabbit skeletal muscle Ca2+
      release channel (ryanodine receptor) activity were investigated in vesicle-45Ca2+
      flux, single channel and [3H]ryanodine binding measurements. In <0.01 microM Ca2+
      media, the highest 45Ca2+ efflux rate was measured in 0.25 M choline-Cl medium
      followed by 0.25 M KCl, choline 4-morpholineethanesulfonic acid (Mes), potassium
      1,4-piperazinediethanesulfonic acid (Pipes), and K-Mes medium. In all five media,
      the 45Ca2+ efflux rates were increased when the free [Ca2+] was raised from <0.01
      microM to 20 microM and decreased as the free [Ca2+] was further increased to 1
      mM. An increase in [KCl] augmented Ca2+-gated single channel activity and
      [3H]ryanodine binding. In [3H]ryanodine binding measurements, bell-shaped Ca2+
      activation/inactivation curves were obtained in media containing different
      monovalent cations (Li+, Na+, K+, Cs+, and choline+) and anions (Cl-, Mes-, and
      Pipes-). In choline-Cl medium, substantial levels of [3H]ryanodine binding were
      observed at [Ca2+] <0.01 microM. Replacement of Cl- by Mes- or Pipes- reduced
      [3H]ryanodine binding levels at all [Ca2+]. In all media, the Ca2+-dependence of
      [3H]ryanodine binding could be well described assuming that the skeletal muscle
      ryanodine receptor possesses cooperatively interacting high-affinity Ca2+
      activation and low-affinity Ca2+ inactivation sites. AMP primarily affected
      [3H]ryanodine binding by decreasing the apparent affinity of the Ca2+
      inactivation site(s) for Ca2+, while caffeine increased the apparent affinity of
      the Ca2+ activation site for Ca2+. Competition studies indicated that ionic
      composition affected Ca2+-dependent receptor activity by at least three different
      mechanisms: (i) competitive binding of Mg2+ and monovalent cations to the Ca2+
      activation sites, (ii) binding of divalent cations to the Ca2+ inactivation
      sites, and (iii) binding of anions to specific anion regulatory sites.

PMID- 8999839
TI  - Protein-tyrosine phosphatase 1B complexes with the insulin receptor in vivo and
      is tyrosine-phosphorylated in the presence of insulin.
AB  - In response to insulin, protein-tyrosine phosphatase 1B (PTPase 1B)
      dephosphorylates 95- and 160-180-kDa tyrosine phosphorylated (PY) proteins
      (Kenner, K. A., Anyanwu, E., Olefsky, J. M., and Kusari, J. (1996) J. Biol. Chem.
      271, 19810-19816). To characterize these proteins, lysates from control and
      insulin-treated cells expressing catalytically inactive PTPase 1B (CS) were
      immunoadsorbed and subsequently immunoblotted using various combinations of
      phosphotyrosine, PTPase 1B, and insulin receptor (IR) antibodies. Anti-PTPase 1B
      antibodies coprecipitated a 95-kDa PY protein from insulin-stimulated cells,
      subsequently identified as the IR beta-subunit. Similarly, anti-IR antibodies
      coprecipitated the 50-kDa PY-PTPase 1B protein from insulin-treated cells. To
      identify PTPase 1B tyrosine (Tyr) residues that are phosphorylated in response to
      insulin, three candidate sites (Tyr66, Tyr152, and Tyr153) were replaced with
      phenylalanine. Replacing Tyr66 or Tyr152 and Tyr153 significantly reduced insulin
      stimulated PTPase 1B phosphotyrosine content, as well as its association with the
      IR. Studies using mutant IRs demonstrated that IR autophosphorylation is
      necessary for the PTPase 1B-IR interaction. These results suggest that PTPase 1B
      complexes with the autophosphorylated insulin receptor in intact cells, either
      directly or within a complex involving additional proteins. The interaction
      requires multiple tyrosine phosphorylation sites within both the receptor and
      PTPase 1B.

PMID- 8999840
TI  - DNA-based loss of specificity mutations. Effects of DNA sequence on the contacted
      and non-contacted base preferences of bacteriophage P22 repressor.
AB  - Although the two central bases of the P22 operator are not contacted by the P22
      repressor, changes in these bases alter the affinity of operator for repressor.
      Previous studies (Wu, L., and Koudelka, G. B. (1993) J. Biol. Chem. 268, 18975
      18981) show that the structure of the P22 repressor-operator complex varies with
      central base sequence. Here we show that central base sequence composition
      affects the strength of two, and likely all, specific amino acid-base pair
      contacts between synthetic P22 operators and P22 repressor. However, altering a
      specific protein-DNA contact via a loss-of-contact mutation in repressor results
      in a loss of specificity at only one contacted position. Thus, only changing the
      sequence of non-contacted bases affects repressor's global base specificity. The
      observed effects of ionic concentration on the affinities of various operators
      for repressor and the DNase I patterns of protein complexes with these binding
      sites indicate certain central base sequences facilitate optimal juxtaposition of
      repressor with its contacted bases, while others prevent it. The existence of
      different structural forms of the repressor-operator complexes explains how the
      relative energetic importance of specific amino acid-base pair edge contacts is
      modulated.

PMID- 8999841
TI  - MinK potassium channels are heteromultimeric complexes.
AB  - MinK is a transmembrane protein of 130 amino acids found in the kidney, heart,
      and vestibular system of mammals. Its expression in Xenopus laevis oocytes
      induces a voltage-dependent potassium current similar to that seen in vivo.
      Indirect evidence has fueled speculation that function requires association of
      MinK and another protein endogenous to oocytes and native tissues. In this
      report, we show that direct covalent modification of an oocyte membrane protein
      alters properties of the MinK ion conduction pore; modified channels exhibit
      decreased potassium conduction and increased permeability to sodium and cesium.
      The modifying reagents, two membrane-impermeant, sulfhydryl-specific
      methanethiosulfonate derivatives, react only from the extracellular solution at
      rates that are determined by the conformational state of the channel. These
      findings indicate that MinK is intimately associated with an oocyte protein whose
      exposure to the external solution changes during channel gating and which acts
      with MinK to establish ion conduction pore function.

PMID- 8999842
TI  - Fatty acids rapidly induce the carnitine palmitoyltransferase I gene in the
      pancreatic beta-cell line INS-1.
AB  - Fatty acids are important metabolic substrates for the pancreatic beta-cell, and
      long term exposure of pancreatic islets to elevated concentrations of fatty acids
      results in an alteration of glucose-induced insulin secretion. Previous work
      suggested that exaggerated fatty acid oxidation may be implicated in this process
      by a mechanism requiring changes in metabolic enzyme expression. We have
      therefore studied the regulation of carnitine palmitoyltransferase I (CPT I) gene
      expression by fatty acids in the pancreatic beta-cell line INS-1 since this
      enzyme catalyzes the limiting step of fatty acid oxidation in various tissues.
      Palmitate, oleate, and linoleate (0.35 mM) elicited a 4-6-fold increase in CPT I
      mRNA. The effect was dose-dependent and was similar for saturated and unsaturated
      fatty acids. It was detectable after 1 h and reached a maximum after 3 h. The
      induction of CPT I mRNA by fatty acids did not require their oxidation, and 2
      bromopalmitate, a nonoxidizable fatty acid, increased CPT I mRNA to the same
      extent as palmitate. The induction was not prevented by cycloheximide treatment
      of cells indicating that it was mediated by pre-existing transcription factors.
      Neither glucose nor pyruvate and various secretagogues had a significant effect
      except glutamine (7 mM) which slightly induced CPT I mRNA. The half-life of the
      CPT I transcript was unchanged by fatty acids, and nuclear run-on analysis showed
      a rapid (less than 45 min) and pronounced transcriptional activation of the CPT I
      gene by fatty acids. The increase in CPT I mRNA was followed by a 2-3-fold
      increase in CPT I enzymatic activity measured in isolated mitochondria. The
      increase in activity was time-dependent, detectable after 4 h, and close to
      maximal after 24 h. Fatty acid oxidation by INS-1 cells, measured at low glucose,
      was also 2-3-fold higher in cells cultured with fatty acid in comparison with
      control cells. Long term exposure of INS-1 cells to fatty acid was associated
      with elevated secretion of insulin at a low (5 mM) concentration of glucose and a
      decreased effect of higher glucose concentrations. It also resulted in a
      decreased oxidation of glucose. The results indicate that the CPT I gene is an
      early response gene induced by fatty acids at the transcriptional level in beta-
      (INS-1) cells. It is suggested that exaggerated fatty acid oxidation caused by
      CPT-1 induction is implicated in the process whereby fatty acids alter glucose
      induced insulin secretion.

PMID- 8999843
TI  - Intronic enhancer activity of the eosinophil-derived neurotoxin (RNS2) and
      eosinophil cationic protein (RNS3) genes is mediated by an NFAT-1 consensus
      binding sequence.
AB  - The eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are
      both small, cationic ribonuclease toxins that are stored in and secreted by
      activated human eosinophilic leukocytes. We have previously shown that optimal
      expression of the EDN gene is dependent on an interaction between an intronic
      enhancer element or elements and the 5' promoter region. Here we present evidence
      demonstrating that the gene encoding ECP is regulated in an analogous fashion and
      that an intronic enhancer element functioning in both genes is a consensus
      binding sequence for the transcription factor NFAT-1. Our initial results
      demonstrate that one or more nuclear proteins isolated from human promyelocytic
      leukemia (HL-60) cells bind specifically at this consensus site (5'-GGAGAA-3')
      within the intron of the EDN gene and that disruption of this sequence reduced
      the characteristic 20-30-fold increase in reporter gene activity observed with
      the tandem EDN promoter/exon 1/intron construct to background levels. The NFAT-1
      consensus site in the ECP gene differs from that found in the EDN gene by a
      single nucleotide (5'-GGAGAG-3'); the conversion of the 3' G to an A resulted in
      a further enhancement of the reporter gene activity supported by the ECP
      promoter/exon 1/intron construct. Interestingly, no "supershift" was observed in
      gel shift assays performed in the presence of anti-NFAT-1 antiserum, suggesting
      that a nuclear protein other than NFAT-1 may be acting at this consensus site.

PMID- 8999844
TI  - Pleiotropic effects of puf interposon mutagenesis on carotenoid biosynthesis in
      Rubrivivax gelatinosus. A new gene organization in purple bacteria.
AB  - Rubrivivax gelatinosus mutants affected in the carotenoid biosynthesis pathways
      were created by interposon mutagenesis within the puf operon. Genetic and
      biochemical analysis of several constructed mutants suggest that at least crtC is
      localized downstream of the puf operon and that it is cotranscribed with this
      operon. Sequence analysis confirmed the genetic data and showed the presence of
      crtD and crtC genes downstream of the puf operon, a localization different from
      that known for other purple bacteria. Inactivation of the crtD gene indicated
      that the two crt genes are cotranscribed and that they are involved not only in
      the hydroxyspheroidene biosynthesis pathway as in Rhodobacter sphaeroides and R.
      capsulatus, but also in the spirilloxanthin biosynthesis pathway. Carotenoid
      genes implicated in the spirilloxanthin biosynthesis pathway were thus identified
      for the first time. Furthermore, analysis of carotenoid synthesis in the mutants
      gave genetic evidence that crtD and crtC genes are cotranscribed with the puf
      operon using the oxygen-regulated puf promoter.

PMID- 8999845
TI  - p120 GAP modulates Ras activation of Jun kinases and transformation.
AB  - Although recent evidence demonstrates that Ras causes transformation by
      activation of multiple downstream pathways, the specific role of non-Raf effector
      pathways is presently unknown. Although Ras causes activation of the Jun NH2
      terminal kinases (JNKs) via a Raf-independent pathway, the contribution of JNK
      activation to Ras transformation and the effector that mediates JNK activation
      have not been established. We observed that a dominant negative mutant of
      SEK1/JNKK, an activator of JNKs, selectively inhibited oncogenic Ras activation
      of JNK and Ras transformation, but not Ras activation of the p42 mitogen
      activated protein kinase. In contrast, overexpression of wild type SEK1 enhanced
      Ras activation of JNK and transforming activity. Thus, JNK activation promotes
      Ras transformation. Furthermore, a dominant negative mutant of p120 GAP
      (designated N-GAP), a candidate Ras effector, blocked Ras, but not Raf,
      transformation and blocked Ras, but not Rac, activation of JNK. Since N-GAP
      overexpression reduced the association of p190 Rac/Rho GAP with endogenous p120
      GAP, N-GAP may form nonproductive complexes with components critical for p120 GAP
      function. In summary, p120 GAP may function as an effector for Ras activation of
      JNK and Ras transformation.

PMID- 8999847
TI  - Reactive cysteines of the yeast plasma-membrane H+-ATPase (PMA1). Mapping the
      sites of inactivation by N-ethylmaleimide.
AB  - We have taken advantage of cysteine mutants described previously (Petrov, V. V.,
      and Slayman, C. W. (1995) J. Biol. Chem. 270, 28535-28540) to map the sites at
      which N-ethylmaleimide (NEM) reacts with the plasma-membrane H+ATPase (PMA)1 of
      Saccharomyces cerevisiae. When membrane vesicles containing the ATPase were
      incubated with NEM, six of nine mutants with single cysteine substitutions showed
      sensitivity similar to the wild-type enzyme. By contrast, C221A and C532A were
      inactivated more slowly than the wild-type control, and the C221, 532A double
      mutant was completely resistant, indicating that Cys-221 and Cys-532 are NEM
      reactive residues. In the presence of 10 mM MgADP, the wild-type ATPase was
      partially protected against NEM; parallel experiments with the C221A and C532A
      mutants showed that the protection occurred at Cys-532, located in or near the
      nucleotide-binding site. Unexpectedly, the inactivation of the C409A ATPase was
      approximately 4-fold more rapid than in the case of the wild-type enzyme.
      Experiments with double mutants made it clear that this resulted from an acidic
      shift in pKa and a consequent acceleration of the reaction rate at Cys-532. One
      simple interpretation is that substitution of Cys-409 leads to a local
      conformational change within the central hydrophilic domain. Consistent with this
      idea, the reaction of fluorescein 5'-isothiocyanate at Lys-474 was also
      stimulated approximately 3. 5-fold by the C409A mutation. Taken together, the
      results of this study provide new information about the reactivity of individual
      Cys residues within the ATPase and pave the way to tag specific sites for
      structural and functional studies of the enzyme.

PMID- 8999846
TI  - Agents that reverse multidrug resistance, tamoxifen, verapamil, and cyclosporin
      A, block glycosphingolipid metabolism by inhibiting ceramide glycosylation in
      human cancer cells.
AB  - We have previously shown that multidrug-resistant cancer cells display elevated
      levels of glucosylceramide (Lavie, Y., Cao, H., Bursten, S. L., Giuliano, A. E.,
      and Cabot, M. C. (1996) J. Biol. Chem. 271, 19530-19536). In this study we used
      the multidrug-resistant human breast cancer cell line MCF-7-Adriamycin-resistant
      (AdrR), which exhibits marked accumulation of glucosylceramide compared with the
      parental MCF-7 wild type (drug-sensitive) cell line, to define the relationship
      between glycolipids and multidrug resistance (MDR). Herein it is shown that
      clinically relevant concentrations of tamoxifen, verapamil, and cyclosporin A,
      all circumventors of MDR, markedly decrease glucosylceramide levels in MCF-7-AdrR
      cells (IC50 values, 1. 0, 0.8, and 2.3 microM, respectively). In intact cells,
      tamoxifen inhibited glycosphingolipid synthesis at the step of ceramide
      glycosylation. In cell-free assays for glucosylceramide synthase, tamoxifen (1:10
      molar ratio with ceramide) inhibited glucosylceramide formation by nearly 50%. In
      cell cultures, inhibition of glucosylceramide synthesis by tamoxifen is
      correlated with its ability to sensitize MCF-7-AdrR cells to Adriamycin toxicity.
      Moreover, treatment of cells with 1-phenyl-2-palmitoylamino-3-morpholino-1
      propanol, an inhibitor of glucosylceramide synthesis, likewise sensitized MCF-7
      AdrR cells to Adriamycin. It is concluded that high cellular levels of
      glucosylceramide are correlated with MDR, and that glycolipids are a target for
      the action of MDR-reversing agents such as tamoxifen. The data entertain the
      notion that drug resistance phenomena are aligned with cell capacity to
      metabolize ceramide.

PMID- 8999848
TI  - Calpain cleavage of focal adhesion proteins regulates the cytoskeletal attachment
      of integrin alphaIIbbeta3 (platelet glycoprotein IIb/IIIa) and the cellular
      retraction of fibrin clots.
AB  - The intracellular thiol protease calpain catalyzes the limited proteolysis of
      various focal adhesion structural proteins and signaling enzymes in adherent
      cells. In human platelets, calpain activation is dependent on fibrinogen binding
      to integrin alphaIIbbeta3 and subsequent platelet aggregation, suggesting a
      potential role for this protease in the regulation of postaggregation responses.
      In this study, we have examined the effects of calpain activation on several
      postaggregation events in human platelets, including the cytoskeletal attachment
      of integrin alphaIIbbeta3, the tyrosine phosphorylation of cytoskeletal proteins,
      and the cellular retraction of fibrin clots. We demonstrate that calpain
      activation in either washed platelets or platelet-rich plasma is associated with
      a marked reduction in platelet-mediated fibrin clot retraction. This relaxation
      of clot retraction was observed in both thrombin and ionophore A23187-stimulated
      platelets. Calcium dose-response studies (extracellular calcium concentrations
      between 0.1 microM and 1 M) revealed a strong correlation between calpain
      activation and relaxed clot retraction. Furthermore, pretreating platelets with
      the calpain inhibitors calpeptin and calpain inhibitor I prevented the calpain
      mediated reduction in clot retraction. Relaxed fibrin clot retraction was
      associated with the cleavage of several platelet focal adhesion structural
      proteins and signaling enzymes, resulting in the dissociation of talin, pp60(c
      )src, and integrin alphaIIbbeta3 from the contractile cytoskeleton and the
      tyrosine dephosphorylation of multiple cytoskeletal proteins. These studies
      suggest an important role for calpain in the regulation of multiple
      postaggregation events in human platelets. The ability of calpain to inhibit clot
      retraction is likely to be due to the cleavage of both structural and signaling
      proteins involved in modulating integrin-cytoskeletal interactions.

PMID- 8999849
TI  - Mutation of an amino acid residue influencing potassium coupling in the glutamate
      transporter GLT-1 induces obligate exchange.
AB  - Glutamate transporters maintain low synaptic concentrations of neurotransmitter
      by coupling uptake to flux of other ions. After cotransport of glutamic acid with
      Na+, the cycle is completed by countertransport of K+. We have identified an
      amino acid residue (glutamate 404) influencing ion coupling in a domain of the
      transporter implicated previously in kainate binding. Mutation of this residue to
      aspartate (E404D) prevents both forward and reverse transport induced by K+.
      Sodium-dependent transmitter exchange and a transporter-mediated chloride
      conductance are unaffected by the mutation, indicating that this residue
      selectively influences potassium flux coupling. The results support a kinetic
      model in which sodium and potassium are translocated in distinct steps and
      suggest that this highly conserved region of the transporter is intimately
      associated with the ion permeation pathway.

PMID- 8999850
TI  - Characterization of the transcriptional regulator YY1. The bipartite
      transactivation domain is independent of interaction with the TATA box-binding
      protein, transcription factor IIB, TAFII55, or cAMP-responsive element-binding
      protein (CPB)-binding protein.
AB  - YY1 is a multifunctional transcription factor implicated in both positive and
      negative regulation of gene expression as well as in initiation of transcription.
      We show that YY1 is ubiquitously expressed in growing, differentiated, and growth
      arrested cells. The protein is phosphorylated and has a half-life of 3.5 h. To
      define functional domains, we have generated a large panel of YY1 mutant
      proteins. These were used to define precisely the DNA-binding domain, the region
      responsible for nuclear localization, and the transactivation domain. The two
      acidic domains at the N terminus each provide about half of the transcriptional
      activating activity. Furthermore, the spacer region between the Gly/Ala-rich and
      zinc finger domains has accessory function in transactivation. YY1 has been shown
      previously to bind to TAFII55, TATA box-binding protein, transcription factor
      IIB, and p300. In addition, we identified cAMP-responsive element-binding protein
      (CBP)-binding protein as a YY1 binding partner. Surprisingly, these proteins did
      not bind to the domains involved in transactivation, but rather to the zinc
      finger and Gly/Ala-rich domains of YY1. Thus, these proteins do not explain the
      transcriptional activating activity of YY1, but rather may be involved in
      repression or in initiation.

PMID- 8999851
TI  - Cryptic self-association sites in type III modules of fibronectin.
AB  - The first type III module of fibronectin (Fn) contains a cryptic site that binds
      Fn and its N-terminal 29 kDa fragment and is thought to be important for fibril
      formation (Morla, A., Zhang, Z., and Ruoslahti, E. (1994) Nature 367, 193-196;
      Hocking, D. C., Sottile, J. , and McKeown-Longo, P. J. (1994) J. Biol. Chem. 269,
      19183-19191). A synthetic 31-mer peptide (NAPQ ... TIPG) derived from the middle
      of domain III1 was also shown to bind Fn, but the site of its interaction was not
      determined (Morla, A., and Ruoslahti, E. (1992) J. Cell Biol. 118, 421-429). By
      affinity chromatography on peptide-agarose, we tested a set of fragments
      representing the entire light chain of plasma Fn. Only 40-kDa Hep-2 (III12-15)
      failed to bind. The concentration of urea required for peak elution of Fn and the
      other fragments decreased in the order Fn > 42-kDa GBF (I6II1-2I7-9) > 19-kDa Fib
      2 (I10-12) > 110-kDa CBF(III2-10) > 29-kDa Fib-1 (I1-I5). Neither Fn nor any of
      the fragments bound immobilized intact III1, confirming the cryptic nature of
      this activity. In an effort to detect interactions between other Fn domains, all
      fragments were coupled to Sepharose, and each fragment was tested on each
      affinity matrix before and after denaturation. The only interaction detected was
      that of fluid phase III1 with immobilized denatured 110-kDa CBF and 40-kDa Hep-2,
      both of which contain type III domains. Analysis of subfragments revealed this
      activity to be dominated by domains III7 and III15. Fn itself did not bind to the
      denatured fragments. Thus, domain III1 contains two cryptic "self-association
      sites," one that is buried in the core of the fold but recognizes many Fn
      fragments when presented as a peptide and another that is concealed in Fn but
      exposed in the native isolated domain and recognizes cryptic sites in two other
      type III domains. These interactions between type III domains could play an
      important role in assembly of Fn multimers in the extracellular matrix.

PMID- 8999853
TI  - Trigger factor associates with GroEL in vivo and promotes its binding to certain
      polypeptides.
AB  - Trigger factor (TF) is a putative molecular chaperone recently found to function
      together with GroEL in the degradation of the fusion protein, CRAG. TF
      overproduction enhanced the ability of GroEL to form complexes with CRAG, as well
      as fetuin or histone. To define further this effect on GroEL binding, affinity
      columns containing a variety of denatured proteins were used. When cell extracts
      were applied onto a fetuin column, both TF and GroEL bound but not GroES. Upon
      ATP addition, TF and GroEL were eluted together and remained tightly associated
      (even in presence of GroES) in complexes containing one TF per GroEL 14-mer.
      Overproduction of TF enhanced the capacity of GroEL to bind to many denatured
      proteins. Moreover, GroEL-TF complexes isolated from such cells showed much
      greater binding capacity than GroEL from TF-deficient cells. Furthermore, the
      addition of pure TF to pure GroEL also enhanced markedly its binding capacity.
      The affinity of GroEL for CRAG also rises during heat shock due to GroEL
      phosphorylation. TF expression, however, did not promote GroEL phosphorylation.
      Moreover, heat shock and TF overproduction affected GroEL binding to other
      denatured polypeptides in distinct ways; only TF promoted binding to certain
      polypeptides, whereas only phosphorylation increased binding to others. Thus,
      association with TF and phosphorylation are independent regulators of GroEL
      function. This enhanced affinity of TF-GroEL complexes for unfolded proteins may
      also be important in protein folding, because TF has prolyl isomerase activity
      and associates with nascent polypeptides.

PMID- 8999852
TI  - Neutrophil-activating peptide-2 and melanoma growth-stimulatory activity are
      functional as monomers for neutrophil activation.
AB  - Neutrophil-activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity
      (MGSA) are members of the chemokine family of inflammatory proteins. The
      structures of NAP-2, determined by x-ray crystallography, and MGSA, elucidated by
      NMR spectroscopy, revealed a tetramer and dimer, respectively. In order to
      address the relevance of multimeric species to their activities on neutrophils,
      analogs of NAP-2 and MGSA were synthesized in which the backbone amide proton of
      Leu-22 in NAP-2, and Val-26 in MGSA, was substituted with the bulky methyl group
      (NH --> NCH3). These analogs were shown to be monomeric by sedimentation
      equilibrium ultracentrifugation studies and were similar to the corresponding
      native protein in assays for neutrophil elastase release and Ca2+ mobilization
      from IL-8R1 and IL-8R2 transformed cells. Sedimentation equilibrium studies of
      the native NAP-2 and MGSA were also carried out to address the association
      behavior. For NAP-2, there was no evidence for the tetramer, but an equilibrium
      between monomers and dimers and the dissociation constant was calculated to be 50
      100 microM. Similarly, MGSA showed a monomer-dimer equilibrium with a Kd of
      approximately 5 microM. The data from the monomeric analogs and also the
      calculation of dissociation constants indicate that NAP-2 and MGSA have a
      tendency to associate above the concentrations required for maximal activity or
      for receptor activation, but at functional concentrations they are predominantly
      monomers.

PMID- 8999854
TI  - Matrix-assisted laser desorption ionization/quadrupole ion trap mass spectrometry
      of peptides. Application to the localization of phosphorylation sites on the P
      protein from Sendai virus.
AB  - The polymerase-associated phosphoprotein (P protein) from Sendai virus, a murine
      Paramyxovirus, is reported in the literature to be a highly phosphorylated
      protein. In vitro studies have detected phosphorylation in different regions of
      the protein, while a single phosphopeptide (identified as the sole
      phosphorylation) site) was observed using in vivo techniques. In this work, two
      phosphorylation sites of the P protein from Sendai virus are localized by a
      direct approach using matrix-assisted laser desorption ionization/quadrupole ion
      trap mass spectrometry. A computer-aided approach is used to confirm peptide
      identification.

PMID- 8999855
TI  - Characterization of hypothermia-induced cellular stress response in mouse
      tissues.
AB  - Cells respond to adverse environmental conditions by expressing heat shock
      proteins, which serve to protect cells from harmful effects of the stress
      conditions. In this study we demonstrated that mice subjected to whole body
      hypothermia induced the cellular stress response, resulting in the increased
      expression of hsp72 mRNA in brain, heart, kidney, liver, and lung. We performed a
      detailed analysis of the major parameters of the stress response and found that
      cold induction of hsp expression is mediated by heat shock factor 1 (HSF1), which
      is also responsible for heat induction of the cellular stress response. However,
      there are differences in the mechanisms of HSF1 activation by hypothermia versus
      hyperthermia, as hypothermia does not cause the hyperphosphorylation of HSF1 that
      is characteristic of heat-activated HSF1.

PMID- 8999856
TI  - Permissive role of nitric oxide in endothelin-induced migration of endothelial
      cells.
AB  - Endothelin (ET) synthesis is enhanced at sites of ischemia or in injured vessels.
      The purpose of this study was to explore the possibility of autocrine stimulation
      of endothelial cell migration by members of the endothelin family. Experiments
      with microvascular endothelial cell transmigration in a Boyden chemotactic
      apparatus showed that endothelins 1 and 3, as well as a selective agonist of ETB
      receptor IRL-1620, equipotently stimulated migration. Endothelial cell migration
      was unaffected by the blockade of ETA receptor, but it was inhibited by ETB
      receptor antagonism. Based on our previous demonstration of signaling from the
      occupied ETB receptor to constitutive nitric oxide (NO) synthase (Tsukahara, H.,
      Ende, H., Magazine, H. I., Bahou, W. F., and Goligorsky, M. S. (1994) J. Biol.
      Chem. 269, 21778-21785), we next examined the contribution of ET-stimulated NO
      production to endothelial cell migration. In three independent cellular systems,
      1) migration and wound healing by microvascular endothelial cells, 2) wound
      healing by Chinese hamster ovary cells stably expressing ETB receptor with or
      without endothelial NO synthase, and 3) application of antisense
      oligodeoxynucleotides targeting endothelial NO synthase in human umbilical vein
      endothelial cells, an absolute requirement for the functional NO synthase in cell
      migration has been demonstrated. These findings establish the permissive role of
      NO synthesis in endothelin-stimulated migration of endothelial cells.

PMID- 8999857
TI  - Binding of upstream stimulatory factor to an E-box in the 3'-flanking region
      stimulates alpha1(I) collagen gene transcription.
AB  - Since several lines of evidence implicate the 3'-flanking region in regulating
      alpha1(I) collagen gene transcription, we analyzed 12. 4-kilobase pairs of 3'
      flanking sequence of the murine alpha1(I) collagen gene for transcriptional
      elements. A region of the 3'-flanking region stimulated expression of the
      heterologous beta-globin gene promoter in an enhancer trap plasmid and of the
      alpha1(I) collagen gene promoter in a collagen-luciferase reporter gene construct
      when located 3' to the luciferase reporter gene. DNase I footprinting analysis
      demonstrated the presence of three regions where DNA binding proteins
      specifically interact within this 3'-stimulatory region. Inspection of the DNA
      sequence revealed a consensus E-box, a binding site for basic helix-loop-helix
      proteins, in one of the protein binding sites. Mobility shift assays demonstrated
      that upstream stimulatory factors (USF) USF-1 and USF-2 bind to this E-box.
      Mutating the E-box in the context of the 3'-flanking region confirmed that it
      contributes to the enhancement of transcriptional activity of the alpha1(I)
      collagen gene promoter. Mutations in all three protein binding sites abolished
      transcriptional activation by the 3'-flanking region, suggesting a complex
      interaction among the trans-acting factors in enhancing transcriptional activity.
      Thus, a region of the 3'-flanking region of the alpha1(I) collagen gene
      stimulates transcription of the alpha1(I) collagen gene promoter, and USF-1 and
      USF-2 contribute to this transcriptional stimulation.

PMID- 8999859
TI  - Replication factor C interacts with the C-terminal side of proliferating cell
      nuclear antigen.
AB  - Replication factor C (RF-C) is a heteropentameric protein essential for DNA
      replication and repair. It is a molecular matchmaker required for loading of
      proliferating cell nuclear antigen (PCNA) onto double-stranded DNA and, thus, for
      PCNA-dependent DNA elongation by DNA polymerases delta and epsilon. To elucidate
      the mode of RF-C binding to the PCNA clamp, modified forms of human PCNA were
      used that could be 32P-labeled in vitro either at the C or the N terminus. Using
      a kinase protection assay, we show that the heteropentameric calf thymus RF-C was
      able to protect the C-terminal region but not the N-terminal region of human PCNA
      from phosphorylation, suggesting that RF-C interacts with the PCNA face at which
      the C termini are located (C-side). A similar protection profile was obtained
      with the recently identified PCNA binding region (residues 478-712), but not with
      the DNA binding region (residues 366-477), of the human RF-C large subunit
      (Fotedar, R., Mossi, R., Fitzgerald, P., Rousselle, T., Maga, G., Brickner, H.,
      Messner, H., Khastilba, S., Hubscher, U., and Fotedar, A., (1996) EMBO J., 15,
      4423-4433). Furthermore, we show that the RF-C 36 kDa subunit of human RF-C could
      interact independently with the C-side of PCNA. The RF-C large subunit from a
      third species, namely Drosophila melanogaster, interacted similarly with the
      modified human PCNA, indicating that the interaction between RF-C and PCNA is
      conserved through eukaryotic evolution.

PMID- 8999858
TI  - Histidine 225, a residue of the NhaA-Na+/H+ antiporter of Escherichia coli is
      exposed and faces the cell exterior.
AB  - Cysteine residues were found nonessential in the mechanism of the NhaA antiporter
      activity of Escherichia coli. The functional C-less NhaA has provided the
      groundwork to study further histidine 225 of NhaA which has previously been
      suggested to play an important role in the activation of NhaA at alkaline pH
      (Rimon, A., Gerchman, Y., Olami, Y., Schuldiner, S. and Padan, E. (1995) J. Biol.
      Chem. 270, 26813-26817). C-less H225C was constructed and shown to possess an
      antiporter activity 60% of that of C-less antiporter and a pH profile similar to
      that of both the C-less or wild-type antiporters. Remarkably, whereas neither the
      wild-type nor the C-less antiporters were affected by N-ethylmaleimide, C-less
      H225C was inhibited by this reagent. To determine the degree of alkylation of the
      antiporter protein by N-ethylmaleimide, antiporter derivatives tagged at their C
      termini with six histidines residues were constructed. Alkylation of C-less H225C
      was measured by labeling of everted membrane vesicles with [14C]N-ethylmaleimide,
      affinity purification of the His-tagged antiporter, and determination of the
      radioactivity of the purified protein. This assay showed that H225C is alkylated
      to a much higher level than any of the native cysteinyl residues of NhaA reaching
      saturation at alkyl/NhaA stoichiometry of 1. The wild-type derivative showed at
      least 10-fold less alkylation even at higher concentrations, suggesting that
      H225C resides in a domain that is much more exposed to N-ethylmaleimide than the
      native cysteinyl residues of NhaA. Since H225C residues both in right-side out
      and inside-out membrane vesicles were quantitatively alkylated by N
      ethylmaleimide, this assay was used to determine the accessibility of H225C to
      other SH reagents by titrating the H225C left free to react with N
      ethylmaleimide, following exposure of the membranes to the reagents. Furthermore,
      since membrane-impermeant probes can react with residues in membrane-embedded
      protein only if accessible to the medium containing the reagent, the assay was
      used to determine the membrane topology of H225C. As expected for a membrane
      permeant probe, p-chloromercuribenzoate reacted with H225C as efficiently as N
      ethylmaleimide in both membrane orientations. Similar results were obtained with
      methanethiosulfonate ethylammonium supporting the recent observations that this
      probe is membrane-permeant. On the other hand, both membrane-impermeant reagents
      p-chloromercuribenzosulfonate and methanethiosulfonate ethyl-trimethyl ammonium
      bromide reacted with H225C 10-fold more in right-side out than in inside-out
      vesicles, and p-chloromercuribenzosulfonate also blocked completely the H225C in
      intact cells. These results strongly suggest that H225C is exposed at the
      periplasmic face of the membrane.

PMID- 8999860
TI  - The regulatory Ser262 of microtubule-associated protein tau is phosphorylated by
      phosphorylase kinase.
AB  - Abnormally phosphorylated tau is the major component of paired helical filaments
      found in the brains of patients suffering from Alzheimer's disease. Therefore,
      the identification of kinases that phosphorylate tau is of considerable interest.
      A DEAE-Sepharose column resolved porcine brain extract into five tau kinase
      activity peaks. Among these peaks, two were completely inhibited by EGTA,
      indicating that these two activity peaks contained Ca2+-dependent tau kinases.
      One of the above two Ca2+-dependent tau kinase activity peaks also contained
      phosphorylase kinase activity. The tau kinase and phosphorylase kinase activities
      associated with this peak could not be separated from each other by Superose 12
      gel filtration, hydroxylapatite, and calmodulin-agarose affinity
      chromatographies. Phosphorylase kinase, purified from rabbit skeletal muscle,
      phosphorylated tau to a stoichiometry of 2.1 mol of phosphate/mol of tau and
      converted tau to a species with a retarded mobility on SDS-polyacrylamide gel
      electrophoresis. The apparent Km and kcat values for tau phosphorylation by
      muscle phosphorylase kinase were 6.9 microM and 47.4 min-1, respectively. As a
      substrate of muscle phosphorylase kinase, phosphorylase was eight times better
      than tau. Sequence analyses of tryptic and thermolytic phosphopeptides derived
      from tau phosphorylated by muscle phosphorylase kinase revealed five
      phosphorylation sites, Ser237, Ser262, Ser285, Ser305, and Ser352. Among these
      sites, Ser262 was previously shown to be phosphorylated in human tau from fetal,
      adult, and Alzheimer's diseased brains (Seubert, P., Mawal-Dewan, M., Barbour,
      R., Jakes, R., Goedert, M., Johnson, G. V. W., Litersky, J. M., Schenk, D.,
      Lieberburg, I., Trojanowski, J. Q., and Lee, V. M. Y. (1995) J. Biol. Chem. 270,
      18917-18922); and its phosphorylation abolished tau's binding to microtubules
      (Drewes, G., Trinczek, B., Illenberger, S., Biernat, J., Schmitt-Ulms, G., Meyer,
      H. E., Mandelkow, E.-M., and Mandelkow, E. (1995) J. Biol. Chem. 270, 7679-7688).
      Slot-blot analysis using a monoclonal antibody against muscle phosphorylase
      kinase and an activity assay using phosphorylase revealed that phosphorylase
      kinase was present in microtubules extensively purified by repeated cycles of
      polymerization and depolymerization. Taken together, these results suggest that
      in neurons, phosphorylase kinase may be one of the kinases that participate in
      the phosphorylation of tau.

PMID- 8999861
TI  - Phosphorylation of platelet pleckstrin activates inositol polyphosphate 5
      phosphatase I.
AB  - Pleckstrin is the major substrate phosphorylated on serine and threonine in
      response to stimulation of human platelets by thrombin (Abrams, C. S., Zhao, W.,
      Belmonte, E., and Brass, L. F. (1995) J. Biol. Chem. 270, 23317-23321). We now
      show that pleckstrin in platelets is in a complex with inositol polyphosphate 5
      phosphatase I (5-phosphatase I). This enzyme hydrolyzes the 5-phosphate from
      inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate and thus
      serves as a calcium signal-terminating enzyme, since the substrates but not the
      products mobilize intracellular calcium. Pleckstrin co-immunoprecipitates with 5
      phosphatase I in homogenates of platelets. Platelet homogenates fractionated by
      anion exchange chromatography show co-elution of pleckstrin and 5-phosphatase I.
      Fractions containing phosphorylated pleckstrin have 7-fold greater 5-phosphatase
      activity than those containing unphosphorylated pleckstrin. Mixing experiments
      with recombinant 5-phosphatase I and pleckstrin in vitro show that they form a
      stoichiometric complex. A mutant form of pleckstrin, in which the serine and
      threonine residues that are phosphorylated by protein kinase C are substituted
      with glutamic acid (pseudophosphorylated pleckstrin), activates recombinant 5
      phosphatase I 2-3-fold while native unphosphorylated pleckstrin does not
      stimulate the enzyme. Thus pleckstrin functions to terminate calcium signaling in
      platelets when it is phosphorylated by binding to and activating 5-phosphatase I.

PMID- 8999862
TI  - Processive degradation of proteins and other catalytic properties of the
      proteasome from Thermoplasma acidophilum.
AB  - Although the structure of the 20 S proteasome from Thermoplasma acidophilum has
      been elucidated, its enzymatic properties have not been explored in depth.
      Thermoplasma proteasomes, which contain one type of active site, exhibit not only
      "chymotrypsin-like" activity (as reported), but also some "post-glutamyl" and
      "trypsin-like" activities. Like eukaryotic proteasomes, its activity can be
      stimulated by SDS, Mg2+, and also guanidine HCl, but not urea. The enzyme was
      strongly inhibited by novel peptide aldehydes with hydrophobic P4 residues, and
      was rapidly inactivated by 3, 4-dichloroisocoumarin (DCI). DCI modified the N
      terminal threonine of the catalytic beta-subunit, the presumed active site
      nucleophile. To define how proteins are degraded, casein was derivatized with
      fluorescein isothiocyanate to facilitate detection of released products by the
      proteasome. Many fluorescent peptides were generated, but the relative amounts of
      different peptides were independent of the duration of the reaction. The rate of
      disappearance of protein substrates paralleled the rate of appearance of small
      products. Unlike conventional proteases, proteasome degrades proteins
      processively without release of polypeptide intermediates. Upon activation by
      SDS, guanidine, heat (55 degrees C), or partial inhibition with DCI, proteasomes
      still functioned processively, but generated a different pattern of peptides
      under each condition. Thus, processivity is an inherent feature of the 20 S
      proteasome, not requiring all active sites or ATP hydrolysis.

PMID- 8999863
TI  - High affinity binding of the pleckstrin homology domain of mSos1 to
      phosphatidylinositol (4,5)-bisphosphate.
AB  - mSos1 has been implicated in coupling mammalian tyrosine kinases to the Ras
      GTPase. Because activation of Ras induced by growth factor stimulation likely
      requires the localization of mSos1 to the plasma membrane, we have investigated
      the possibility that the PH domain of mSos1 might mediate an interaction of mSos1
      with phospholipid membranes. A glutathione S-transferase fusion protein
      containing the pleckstrin homology (PH) domain of mSos1 bound specifically and
      tightly to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) with a Kd of 1.8 +/-
      0.4 microM. This interaction was saturable and was competed away with the soluble
      head group of PI(4,5)P2, inositol 1,4, 5-triphosphate. Substitution of Arg452
      within the PH domain with Ala had only a slight effect on binding to PI(4,5)P2,
      whereas substitution of Arg459 severely compromised the ability of the mSos1 PH
      domain to bind to PI(4,5)P2 containing vesicles. Purified full-length mSos1 and
      mSos1 complexed with Grb2 were also tested for binding to various phosphoinositol
      derivatives and demonstrated a specific interaction with PI(4,5)P2, although
      these interactions were weaker (Kd = approximately 53 and approximately 69
      microM, respectively) than that of the PH domain alone. These findings suggest
      that the PH domain of mSos1 can interact in vitro with phospholipid vesicles
      containing PI(4,5)P2 and that this interaction is facilitated by the ionic
      interaction of Arg459 with the negatively charged head group of PI(4,5)P2. The
      association of the mSos1 PH domain with phospholipid may therefore play a role in
      regulating the function of this enzyme in vivo.

PMID- 8999864
TI  - Similarities of integumentary mucin B.1 from Xenopus laevis and prepro-von
      Willebrand factor at their amino-terminal regions.
AB  - Frog integumentary mucin B.1 (FIM-B.1) contains various cysteine-rich modules. In
      the past, a COOH-terminal "cystine knot" motif has been found that is similar to
      von Willebrand factor; this region is generally known to be responsible for
      dimerization processes. Furthermore, a "complement control protein" motif is
      present as an internal cysteine-rich domain in FIM-B.1. We characterize here the
      missing 75% toward the NH2 terminus of the FIM-B.1 precursor by molecular
      cloning. Analogous to prepro-von Willebrand factor, four elements with
      considerable similarity to D-domains are present (i.e. D1-D2-D'-D3). These
      domains have been described as essential for the multimerization of von
      Willebrand factor. Thus, the general structure of FIM-B.1 resembles that of the
      human mucin MUC2 as well as prepro-von Willebrand factor; these three molecules
      at least seem to share common structural elements allowing similar
      multimerization mechanisms.

PMID- 8999865
TI  - Identification of a hydrophobic exosite on tissue type plasminogen activator that
      modulates specificity for plasminogen.
AB  - A wide variety of important biological processes, including both the formation
      and dissolution of blood clots, depend on specific cleavage of individual target
      proteins by serine proteases. For example, tissue type plasminogen activator (t
      PA), a trypsin-like enzyme that catalyzes the rate-limiting step of the
      endogenous fibrinolytic cascade, has only one known substrate in vivo, a single
      peptide bond (Arg561-Val562) in the proenzyme plasminogen. We have previously
      suggested that the specificity of t-PA for plasminogen is mediated in part by
      direct protein-protein interactions between the protease domain of t-PA and
      plasminogen that are distinct from those occurring within t-PA's active site. We
      demonstrate in this study that residues 420-423 of t-PA, which form a fully
      solvent-exposed, hydrophobic region of a surface loop mapping near one edge of
      the active site of t-PA, form, or are essential for the integrity of, an
      important, secondary site of interaction between t-PA and plasminogen that
      significantly modulates the rate of plasminogen activation in the absence, but
      not the presence, of fibrin. Identification of this secondary site of interaction
      between t-PA and plasminogen provides new insight into molecular details of the
      evolution of stringent substrate specificity by t-PA and suggests a novel
      strategy to enhance the fibrin dependence of plasminogen activation by t-PA.
      While the activity of wild type t-PA is stimulated by fibrin by a factor of
      approximately 650, the activity of two variants characterized in this study, t
      PA/R275E,P422G and t-PA/R275E,P422E, is stimulated by a factor of approximately
      39,000 or 61,000, respectively. It is therefore possible that, compared with wild
      type t-PA, the two variants would display enhanced "clot selectivity" in vivo due
      to reduced activity in the circulation but full activity at a site of fibrin
      deposition.

PMID- 8999866
TI  - Temporal activation of Ca2+-calmodulin-sensitive protein kinase type II is
      obligate for adipogenesis.
AB  - Differentiation of 3T3-L1 embryonic fibroblasts to adipocytes in response to
      induction by dexamethasone and isobutylmethylxanthine is blocked by inhibitors of
      Ca2+-calmodulin-sensitive protein kinase type II, but not by inhibitors of
      protein kinase A or protein kinase C. CaM kinase II displays a biphasic increase
      in autonomous activity, rising after an initial transient peak from 1 to 15 h,
      declining at 24 h, followed by a sustained rise from 24 to 48 h, which is 2. 5
      fold greater than basal values at induction of adipogenesis. Adipogenesis was
      blocked effectively by CaM kinase II inhibitors, either KN-62 or KN-93, if the
      inhibitors are introduced at 6 h and maintained until 12 h of induction of
      adipogenesis. Equally effective, however, is inhibition of CaM kinase II activity
      at 24-48 h after induction, during the later phase of autonomous CaM kinase
      activity. Inhibition of cultures with KN-62 or KN-93 either for 0 to 6 h or for
      12 to 24 h failed to influence adipogenesis. Two temporally-distinct phases of
      CaM kinase II activation, either 6 to 12 h or 24 to 48 h, if inhibited with
      either KN-62 or KN-93, blocked the conversion to adipocytes. Thus, a biphasic
      activation of CaM kinase II is obligate for the progression of the embryonic
      fibroblasts to adipocytes. Inhibition of either phase of CaM kinase activity
      blocks adipogenesis and expression of several intermediate early gene products.

PMID- 8999867
TI  - Mutation of Asn111 in the third transmembrane domain of the AT1A angiotensin II
      receptor induces its constitutive activation.
AB  - A preliminary model of the rat AT1A angiotensin II (AII) receptor (Joseph, M. P.,
      Maigret, B., Bonnafous J.-C., Marie, J., and Scheraga, H. A. (1995) J. Protein
      Chem. 14, 381-398) has predicted an interaction between Asn111 located in
      transmembrane domain (TM) III and Tyr292 (TM VII) in the nonactivated receptor; a
      disruption of this interaction upon AII activation would allow Tyr292 to interact
      with the conserved Asp74 (TM II). The previous verification that Tyr292 is
      essential for receptor coupling to phospholipase C (Marie, J., Maigret, B.,
      Joseph, M. P., Larguier, R., Nouet, S., Lombard, C., and Bonnafous, J.-C. (1994)
      J. Biol. Chem. 269, 20815-20818) prompted us to check the possible alterations in
      receptor properties upon Asn111 --> Ala mutation. The mutated receptor (N111A)
      displayed: (i) strong constitutive activity, with amplification of the maximal
      phospholipase C response to AII; (ii) agonist behavior of the AT2-specific ligand
      CGP 42112A, [Sar1, Ile8]AII, and [Sar1,Ala8]AII, antagonists of the wild-type
      receptor; (iii) inverse agonism behavior of the non-peptide ligands DuP 753, LF 7
      0156, and LF 8-0129. The results are discussed in the light of the allosteric
      ternary complex models and other described examples of constitutive activation of
      G protein-coupled receptors.

PMID- 8999868
TI  - Cloning of human 2H9 heterogeneous nuclear ribonucleoproteins. Relation with
      splicing and early heat shock-induced splicing arrest.
AB  - Using antibody 2H9 from our heterogeneous nuclear ribonucleoproteins (anti-hnRNP)
      monoclonal antibody library, we previously showed in HeLa cells that a 35-37-kDa
      protein doublet switches from the hnRNP complexes to the nuclear matrix following
      a 10-min heat shock at 45 degrees C (1 Lutz, Y., Jacob, M., and Fuchs, J. P.
      (1988) Exp. Cell Res. 175, 109-124). cDNA cloning and sequencing revealed an
      hnRNP protein (2H9) which is a new member of the hnRNP F, H/H' family. Protein
      2H9 displays two consensus sequence-type RNA binding domains (CS-RBD) showing 80
      90% homology with two of the three CS-RBDs of hnRNP F and H/H'. Another common
      feature is the presence of two glycine/tyrosine-rich auxiliary domains located at
      the C terminus and between the two CS-RBDs. At the functional level we show that
      specific anti-2H9 peptide antibodies can directly inhibit an in vitro splicing
      system. Moreover, the 2H9 protein doublet is no more present in nuclear extracts
      from such briefly stressed cells, which interestingly correlates with the
      inability of these extracts to catalyze in vitro splicing reactions. Taken
      together, our data suggest that these proteins are involved in the splicing
      process and also participate in early heat shock-induced splicing arrest by
      transiently leaving the hnRNP complexes. These 2H9 proteins, which are encoded by
      a single gene located on human chromosome 10, were also found to be associated
      with nuclear bodies in situ.

PMID- 8999869
TI  - The salivary lipocalin von Ebner's gland protein is a cysteine proteinase
      inhibitor.
AB  - The lipocalins make up a heterogeneous superfamily of proteins. Although showing
      almost no sequence homology, they share very similar secondary and tertiary
      structures. Their ability to bind hydrophobic ligands is well established, but
      the physiological function of most lipocalins remains unclear. The lipocalin from
      the human Von Ebner's Gland of the tongue (VEGh) contains three sequence motifs
      corresponding with the papain-binding domains of cystatins, a family of naturally
      occurring cysteine proteinase inhibitors. We found that VEGh inhibited papain
      activity to a similar extent as salivary cystatin S. Furthermore, synthetic
      peptides derived from VEGh and cystatin C, comprising these three motifs,
      inhibited papain, too. We conclude that VEGh is a physiological inhibitor of
      cysteine proteinases and therefore can play a role in the control of inflammatory
      processes in oral and ocular tissues.

PMID- 8999870
TI  - Molecular cloning, characterization, and regulation of the human mitochondrial
      serine hydroxymethyltransferase gene.
AB  - The human mitochondrial serine hydroxymethyltransferase (mSHMT) gene was
      isolated, sequenced, and characterized. The 4.5-kilobase gene contains 10 introns
      and 11 exons, with all splice junctions conforming to the GT/AG rule. The 5'
      promoter region contains consensus motifs for several regulatory proteins
      including PEA-3, Sp-1, AP-2, and a CCCTCCC motif common to many genes expressed
      in liver. Consensus TATA or CAAT sequence motifs are not present, and primer
      extension and 5'-rapid amplification of cDNA ends studies suggest that
      transcription initiation occurs at multiple sites. The mitochondrial leader
      sequence region of the deduced mRNA contains two potential ATG start sites, which
      are encoded by separate exons. The intervening 891-base pair intron contains
      consensus promoter elements suggesting that mSHMT may be transcribed from
      alternate promoters. 5'-Rapid amplification of cDNA ends analysis demonstrated
      that the first ATG is transcribed in human MCF-7 cells. However, transfection of
      Chinese hamster ovary cells deficient in mSHMT activity with the human mSHMT gene
      lacking exon 1 overcame the cell's glycine auxotrophy and restored intracellular
      glycine concentrations to that observed in wild-type cells, showing that exon 1
      is not essential for mSHMT localization or activity and that translation
      initiation from the second ATG is sufficient for mSHMT import into the
      mitochondria. Mitochondrial SHMT mRNA levels in MCF-7 cells did not vary during
      the cell cycle and were not affected by the absence of glycine, serine, folate,
      thymidylate, or purines from the media.

PMID- 8999871
TI  - Squamous cell carcinoma antigen 2 is a novel serpin that inhibits the
      chymotrypsin-like proteinases cathepsin G and mast cell chymase.
AB  - The squamous cell carcinoma antigen (SCCA) serves as a serological marker for
      more advanced squamous cell tumors. Molecular cloning of the SCCA genomic region
      revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2. Analysis of
      the primary amino acid sequences shows that both genes are members of the high
      molecular weight serpin superfamily of serine proteinase inhibitors. Although
      SCCA1 and SCCA2 are nearly identical in primary structure, the reactive site loop
      of each inhibitor suggests that they may differ in their specificity for target
      proteinases. SCCA1 has been shown to be effective against papain-like cysteine
      proteinases. The purpose of this study was to determine whether SCCA2 inhibited a
      different family of proteolytic enzymes. Using recombinant DNA techniques, we
      prepared a fusion protein of glutathione S-transferase and full-length SCCA2 .
      The recombinant SCCA2 was most effective against two chymotrypsin-like
      proteinases from inflammatory cells, but was ineffective against papain-like
      cysteine proteinases. Serpin-like inhibition was observed for both human
      neutrophil cathepsin G and human mast cell chymase. The second order rate
      constants for these associations were on the order of approximately 1 x 10(5) M-1
      s-1 and approximately 3 x 10(4) M-1 s-1 for cathepsin G and mast cell chymase,
      respectively. Moreover, SCCA2 formed SDS-stable complexes with these proteinases
      at a stoichiometry of near 1:1. These data showed that SCCA2 is a novel inhibitor
      of two physiologically important chymotrypsin-like serine proteinases.

PMID- 8999872
TI  - Association of csk-homologous kinase (CHK) (formerly MATK) with HER-2/ErbB-2 in
      breast cancer cells.
AB  - Protein-tyrosine kinases, such as HER-2/ErbB-2, have been specifically linked to
      breast cancer. The Csk-homologous kinase (CHK), formerly MATK, is a tyrosine
      kinase that contains the Src homology 2 and 3 (SH2 and SH3) domains and
      demonstrates homology ( approximately 50%) to the Csk tyrosine kinase. Like Csk,
      CHK is able to phosphorylate and inactivate Src family kinases. In this report,
      we investigated whether CHK is expressed in breast cancer tissues and whether it
      participates in the ErbB-2 signaling pathway in T47D and MCF-7 breast cancer cell
      lines. Immunostaining of the CHK protein in breast tissues demonstrated that
      primary invasive ductal carcinomas, stage II (13 of 15 cases) and stage I (8 of
      15 cases), expressed the CHK protein, while this protein was not detected in the
      adjacent normal tissues from the same patients. To study the role of CHK in the
      ErbB-2 signaling pathway, glutathione S-transferase fusion proteins containing
      the SH2 and SH3 domains of CHK were generated. CHK-SH2 and CHK-SH3-SH2, but not
      CHK-SH3 or CHK-NH2-SH3, precipitated the tyrosine-phosphorylated ErbB-2 upon
      stimulation with heregulin. EGF or interleukin-6 stimulation of T47D cells failed
      to induce CHK-SH2 association with ErbB-2, the EGF-receptor, or the interleukin-6
      receptor. In vivo association of the tyrosine-phosphorylated ErbB-2 with CHK was
      observed in co-immunoprecipitation studies with anti-CHK antibodies. EGF-R, ErbB
      3, and ErbB-4 were not detected in the CHK immunoprecipitates or in the
      precipitates of the GST-SH2 fusion proteins of CHK, suggesting that the
      association of CHK with ErbB-2 upon heregulin stimulation is receptor-specific
      (ErbB-2) and ligand-specific (heregulin). These results indicate that CHK might
      participate in signaling in breast cancer cells by associating, via its SH2
      domain, with ErbB-2 following heregulin stimulation.

PMID- 8999873
TI  - Examination of substrate binding in thiamin diphosphate-dependent transketolase
      by protein crystallography and site-directed mutagenesis.
AB  - The three-dimensional structure of the quaternary complex of Saccharomyces
      cerevisiae transketolase, thiamin diphosphate, Ca2+, and the acceptor substrate
      erythrose-4-phosphate has been determined to 2.4 A resolution by protein
      crystallographic methods. Erythrose-4-phosphate was generated by enzymatic
      cleavage of fructose-6-phosphate. The overall structure of the enzyme in the
      quaternary complex is very similar to the structure of the holoenzyme; no large
      conformational changes upon substrate binding were found. The substrate binds in
      a deep cleft between the two subunits. The phosphate group of the substrate
      interacts with the side chains of the conserved residues Arg359, Arg528, His469,
      and Ser386 at the entrance of this cleft. The aldehyde moiety of the sugar
      phosphate is located in the vicinity of the C-2 carbon atom of the thiazolium
      ring of the cofactor. The aldehyde oxygen forms hydrogen bonds to the side chains
      of the residues His30 and His263. One of the hydroxyl groups of the sugar
      phosphate forms a hydrogen bond to the side chain of Asp477. The preference of
      the enzyme for donor substrates with D-threo configuration at the C-3 and C-4
      positions and for alpha-hydroxylated acceptor substrates can be understood from
      the pattern of hydrogen bonds between enzyme and substrate. Amino acid
      replacements by site-directed mutagenesis of residues Arg359, Arg528, and His469
      at the phosphate binding site yield mutant enzymes with considerable residual
      catalytic activity but increased Km values for the donor and in particular
      acceptor substrate, consistent with a role for these residues in phosphate
      binding. Replacement of Asp477 by alanine results in a mutant enzyme impaired in
      catalytic activity and with increased Km values for donor and acceptor
      substrates. These findings suggest a role for this amino acid in substrate
      binding and catalysis.

PMID- 8999874
TI  - Generation of Alzheimer amyloid beta peptide through nonspecific proteolysis.
AB  - Polymerization of Alzheimer amyloid beta peptide (Abeta) into amyloid fibrils is
      associated with resistance to proteolysis and tissue deposition. Here, it was
      investigated whether Abeta might be generated as a protease-resistant core from a
      polymerized precursor. A 100-amino acid C-terminal fragment of the Alzheimer beta
      amyloid precursor protein (C100), containing the Abeta and cytoplasmic domains,
      polymerized both when inserted into membranes and after purification. When
      subjected to digestion using the nonspecific enzyme proteinase K, the cytoplasmic
      domain of C100 was degraded, whereas the Abeta domain remained intact. In
      contrast, dissociated C100 polymers were almost completely degraded by proteinase
      K. Mammalian cells transfected with the human Alzheimer beta-amyloid precursor
      gene contained a fragment corresponding to C100, which needed similar harsh
      conditions to be dissolved, as did polymers formed by purified C100. Hence, it
      was concluded that C100 polymers are formed in mammalian cells. These results
      suggest that the C terminus of Abeta can be generated by nonspecific proteases,
      acting on a polymerized substrate, rather than a specific gamma-secretase. This
      offers an explanation of how the Abeta peptide can be formed in organelles
      containing proteases capable of cleaving most peptide bonds.

PMID- 8999875
TI  - Stress-inducible, murine protein mSTI1. Characterization of binding domains for
      heat shock proteins and in vitro phosphorylation by different kinases.
AB  - We have recently isolated the cDNA for the murine homologue of the stress
      inducible phosphoprotein STI1 (also known as IEF SSP 3521 or p60). STI1 was
      previously shown to be 2-fold up-regulated in MRC-5 fibroblasts upon viral
      transformation and to exist in a macromolecular complex with heat shock proteins
      of the HSP 70 and 90 families. By peptide-sequencing we have identified the two
      heat shock proteins that bind to murine STI1 (mSTI1) as HSC 70 and HSP 84/86. We
      describe two separate binding regions within mSTI1 for the two heat shock
      proteins. In the presence of cell extracts, the N-terminal region of mSTI1 binds
      preferentially to HSC 70, whereas the C-terminal portion of the molecule promotes
      the binding of HSP 84/86. Heat treatment caused a strong induction of mSTI1
      message without affecting the steady-state level of the protein significantly. In
      addition, heat treatment led to changes in the isoform-composition of mSTI1.
      pp70(s6k), pp90(rsk), and mitogen-activated protein kinase-activated protein
      kinase 2 were tested as possible STI1 kinases in vitro using recombinant mSTI1 as
      a substrate: only pp90(rsk) was able to phosphorylate recombinant mSTI1. In vitro
      kinase assays using casein kinase II suggest serine 189 to be a likely
      phosphorylation site in mSTI1.

PMID- 8999876
TI  - Human transcription-repair coupling factor CSB/ERCC6 is a DNA-stimulated ATPase
      but is not a helicase and does not disrupt the ternary transcription complex of
      stalled RNA polymerase II.
AB  - Transcription is coupled to repair in Escherichia coli and in humans. Proteins
      encoded by the mfd gene in E. coli and by the ERCC6/CSB gene in humans, both of
      which possess the so-called helicase motifs, are required for the coupling
      reaction. It has been shown that the Mfd protein is an ATPase but not a helicase
      and accomplishes coupling, in part, by disrupting the ternary complex of E. coli
      RNA polymerase stalled at the site of DNA damage. In this study we overproduced
      the human CSB protein using the baculovirus vector and purified and characterized
      the recombinant protein. CSB has an ATPase activity that is stimulated strongly
      by DNA; however, it neither acts as a helicase nor does it dissociate stalled RNA
      polymerase II, suggesting a coupling mechanism in humans different from that in
      prokaryotes. CSB is a DNA-binding protein, and it also binds to XPA, TFIIH, and
      the p34 subunit of TFIIE. These interactions are likely to play a role in
      recruiting repair proteins to ternary complexes formed at damage sites.

PMID- 8999877
TI  - Effect of the amino acid attached to Escherichia coli initiator tRNA on its
      affinity for the initiation factor IF2 and on the IF2 dependence of its binding
      to the ribosome.
AB  - We show that the nature of the amino acid in the formylaminoacyl-tRNA influences
      initiation factor (IF) 2 dependence of its ribosome binding and that this IF2
      dependence reflects the relative affinity of the formylaminoacyl-tRNA for the
      initiation factor IF2. We compared the template-dependent ribosome binding
      activities, in the presence of initiation factors, of wild type and anticodon
      sequence mutants of Escherichia coli initiator tRNAs that carry formylmethionine
      (fMet), formylglutamine (fGln), or formylvaline (fVal). The fGln-tRNA bound less
      well than fMet-tRNA whereas the fVal-tRNA bound as well as fMet-tRNA. The rate
      and extent of binding of fGln-tRNA to the ribosome was significantly increased by
      further addition of purified initiation factor IF2. In contrast, the binding of
      fVal-tRNA or fMet-tRNA was not affected much by the addition of IF2. Using gel
      mobility shift assay, we have measured the apparent Kd values of the
      IF2.formylaminoacyl-tRNA binary complexes. These are 1.8, 3.5, and 10.5 microM
      for fMet-tRNA, fVal-tRNA, and fGln-tRNA, respectively.

PMID- 8999879
TI  - Cytoskeleton reorganization induces the urokinase-type plasminogen activator gene
      via the Ras/extracellular signal-regulated kinase (ERK) signaling pathway.
AB  - Urokinase-type plasminogen activator (uPA) expression is induced upon
      cytoskeletal reorganization (CSR) by a mechanism independent of protein kinase C
      and cAMP protein kinase in nontransformed renal epithelial (LLC-PK1) cells. This
      CSR-dependent uPA gene activation is mediated by an AP-1-recognizing element
      located 2 kilobases upstream of the transcription initiation site. The
      phosphorylation of c-Jun, a component of AP-1, is induced by CSR, which seems to
      increase both the activity and stability of c-Jun (Lee, J. S., von der Ahe, D.,
      Kiefer, B., and Nagamine, Y. (1993) Nucleic Acids Res. 21, 3365-3372). It has
      been shown that c-Jun is phosphorylated by members of the mitogen-activated
      protein kinase family, i.e. ERKs and JNKs. ERKs are activated through a growth
      factor-coupled Ras/Raf-dependent signaling pathway, while JNKs are activated
      through a stress-induced signaling pathway. Although CSR induces both ERK-2 and
      JNK activity, JNK does not seem to be involved in the uPA gene induction because
      UV irradiation, which activates JNK as efficiently as CSR, does not activate the
      uPA promoter. Further analysis showed the involvement of SOS, Ras, and Raf-1 in
      the pathway induced by CSR. Our results suggest that cells sense changes in cell
      morphology using the cytoskeleton as a sensor and respond by activating the ERK
      involving signaling pathway from within the cell.

PMID- 8999878
TI  - Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct
      cellular locations.
AB  - The beta-amyloid precursor protein (betaAPP) is a transmembrane protein that is
      exclusively phosphorylated on serine residues within its ectodomain. To identify
      the cellular site of betaAPP phosphorylation, we took advantage of an antibody
      that specifically detects the free C terminus of beta-secretase-cleaved betaAPP
      containing the Swedish missense mutation (APPssw-beta). This antibody previously
      established the cellular location of the beta-secretase cleavage of Swedish
      betaAPP as a post-Golgi secretory compartment (Haass, C., Lemere, C., Capell, A.,
      Citron, M., Seubert, P., Schenk, D., Lannfelt, L., and Selkoe, D. J. (1995)
      Nature Med. 1, 1291-1296). We have now localized the selective ectodomain
      phosphorylation of betaAPP to the same compartment. Moreover, the phosphorylation
      sites of betaAPP were identified at Ser198 and Ser206 of betaAPP695 by tryptic
      peptide mapping, mass spectrometry, and site-directed mutagenesis. Intracellular
      phosphorylation of betaAPP was inhibited by Brefeldin A and by incubating cells
      at 20 degrees C, thus excluding phosphorylation in the endoplasmic reticulum or
      trans-Golgi network. Ectodomain phosphorylation within a post-Golgi compartment
      occurred not only with mutant Swedish betaAPP, but also with wild type betaAPP.
      In addition to phosphorylation within a post-Golgi compartment, betaAPP was also
      found to undergo phosphorylation at the cell surface by an ectoprotein kinase.
      Therefore, this study revealed two distinct cellular locations for betaAPP
      phosphorylation.

PMID- 8999880
TI  - Protein phosphorylation affects binding of the Escherichia coli transcription
      activator UhpA to the uhpT promoter.
AB  - Expression of the Escherichia coli sugar phosphate transporter UhpT is induced by
      extracellular glucose 6-phosphate through a transmembrane signaling process
      dependent on the sensor kinase UhpB and the UhpT homolog, UhpC. These proteins
      are thought to regulate the phosphorylation of the transcription activator, UhpA.
      To examine the effect of protein phosphorylation on the binding of UhpA to target
      sequences in the uhpT promoter region, the UhpA protein was overexpressed and
      purified. Purified UhpA was phosphorylated by acetyl phosphate in a reaction that
      was dependent on Mg2+ and on the presence of aspartate 54, the site of
      phosphorylation in homologous response regulators. Gel electrophoretic mobility
      shift and DNase I and hydroxyl radical protection assays showed that UhpA bound
      specifically to the region of the uhpT promoter extending from -80 to -50 bp,
      relative to the transcription start site. At higher concentrations of UhpA,
      binding was extended to the -32 region. Binding to the -64 element exhibited
      positive cooperativity and was stimulated severalfold by phosphorylation of UhpA,
      whereas extension to the downstream region was more strongly affected by
      phosphorylation. The consensus sequences for the high affinity UhpA-binding sites
      in the -64 element and for the downstream, low affinity sites are proposed. The
      pattern of in vitro binding by UhpA agreed with the in vivo observations that
      phosphorylation-independent assembly of the transcription initiation complex can
      occur at elevated concentrations of UhpA.

PMID- 8999882
TI  - Expression of neuronal traits in pancreatic beta cells. Implication of neuron
      restrictive silencing factor/repressor element silencing transcription factor, a
      neuron-restrictive silencer.
AB  - Pancreatic beta cells (insulin-producing cells) and neuronal cells share a large
      number of similarities. Here, we investigate whether the same mechanisms could
      control the expression of neuronal genes in both neurons and insulin-producing
      cells. For that purpose, we tested the role of the transcriptional repressor
      neuron-restrictive silencing factor/repressor element silencing transciption
      factor (NRSF/REST) in the expression of a battery of neuronal genes in insulin
      producing cells. NRSF/REST is a negative regulator of the neuronal fate. It is
      known to silence neuronal-specific genes in non-neuronal cells. We demonstrate
      that, as in the case of the neuronal pheochromocytoma cell line PC12, mRNA coding
      for NRSF/REST is absent from the insulinoma cell line INS-1 and from three other
      insulin- and glucagon-producing cell lines. NRSF/REST activity is also absent
      from insulin-producing cell lines. Transient expression of REST in insulin
      producing cell lines is sufficient to silence a reporter gene containing a
      NRSF/REST binding site, demonstrating the role of NRSF/REST in the expression of
      neuronal markers in insulin-producing cells. Finally, by searching for the
      expression of NRSF/REST-regulated genes in insulin-producing cells, we increased
      the list of the genes expressed in both neurons and insulin-producing cells.

PMID- 8999881
TI  - An intracellular calcium signal activates p70 but not p90 ribosomal S6 kinase in
      liver epithelial cells.
AB  - In the rat liver epithelial cell lines GN4 and WB, angiotensin II (Ang II)
      activates the Gq class of regulatory G-proteins, increasing intracellular
      calcium, protein kinase C activity, and protein tyrosine phosphorylation. We
      compared the ability of Ang II and other compounds that increase intracellular
      calcium (i.e. the calcium ionophore A23187 and thapsigargin) or protein kinase C
      activity (the phorbol ester 12-O-tetradecanoylphorbol-13-acetate) to activate p70
      ribosomal S6 kinase (p70(S6K)) and p90 ribosomal S6 kinase (p90(RSK)). In GN4
      cells, increasing intracellular calcium stimulated p70(S6K) activity in a
      rapamycin- and wortmannin- sensitive manner, but did not affect p90(RSK)
      activity. In contrast, 12-O-tetradecanoylphorbol-13-acetate strongly activated
      p90(RSK) but only weakly stimulated p70(S6K). The ability of calcium to activate
      p70(S6K) was confirmed by blocking the A23187-dependent activation through
      chelation of extracellular calcium with EGTA; the effect of thapsigargin was
      inhibited by the cell permeant chelator bis-(o-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM). Similarly, BAPTA-AM
      prevented the activation of p70(S6K) by Ang II, suggesting that this signal was
      largely calcium-dependent. In contrast, the Ang II-dependent activation of
      mitogen-activated protein kinase and p90(RSK) was not inhibited but was enhanced
      by BAPTA-AM. These results show that in GN4 cells, Ang II selectively activates
      p70(S6K) through effects on calcium, p90(RSK) through effects on protein kinase
      C. The activation of p70(S6K) by calcium stimuli or Ang II was independent of
      calmodulin but correlated well with the activation of the recently identified,
      nonreceptor calcium-dependent tyrosine kinase (CADTK)/PYK-2. Both calcium- and
      Ang II-dependent activation of p70(S6K) were attenuated by the tyrosine kinase
      inhibitor genistein, and activation of p70(S6K) was higher in GN4 than WB cells,
      correlating with the increased expression and activation of CADTK/PYK-2 in GN4
      cells. In summary, these results demonstrate that intracellular calcium
      selectively activates p70(S6K) in GN4 cells, consistent with increased CADTK/PYK
      2 signaling in these cells.

PMID- 8999883
TI  - Metabolism of homocysteine thiolactone in human cell cultures. Possible mechanism
      for pathological consequences of elevated homocysteine levels.
AB  - Editing of the non-protein amino acid homocysteine, a frequent type of error
      correcting process in amino acid selection for protein synthesis by an aminoacyl
      tRNA synthetase, results in formation of a cyclic thioester, homocysteine
      thiolactone. Here it is shown that human cells in which homocysteine metabolism
      is deregulated by a mutation in the cystathionine beta-synthase gene and/or by an
      antifolate drug, aminopterin (which prevents remethylation of homocysteine to
      methionine by methionine synthase), produce more homocysteine thiolactone, in
      addition to homocysteine, than unaffected cells. The thiolactone is incorporated
      into cellular and extracellular proteins, in addition to being secreted and
      hydrolyzed to homocysteine. Experiments with model proteins and amino acids
      suggest that the mechanism of incorporation involves acylation of side chain
      amino groups of lysine residues by the activated carboxyl group of the
      thiolactone. The metabolic conversion of homocysteine to homocysteine thiolactone
      and the reactivity of the thiolactone toward proteins may explain pathological
      consequences of elevated levels of homocysteine such as observed in vascular
      disease.

PMID- 8999885
TI  - The role of cysteine residues in the rearrangement of uridine to pseudouridine
      catalyzed by pseudouridine synthase I.
AB  - Escherichia coli tRNA pseudouridine synthase I (PSUI) catalyzes the conversion of
      uridine residues to pseudouridine in positions 38, 39, and 40 of various tRNA
      molecules. In previous biochemical studies with this enzyme (Kammen, H. O.,
      Marvel, C. C., Hardy, L., and Penhoet, E. E. (1988) J. Biol. Chem. 263, 2255
      2263) it was reported that cysteine residues are important in maintaining the
      active structure of the enzyme and are possibly involved in the catalytic
      reaction mechanism via a covalent cysteine intermediate. In order to further
      investigate the biochemical properties of PSUI, a high level expression and
      purification system for the enzyme and its corresponding mutants was developed.
      PSUI has three cysteine residues among 270 amino acids. In the present
      investigation, each cysteine residue was individually changed to serine and
      alanine. In addition, a triple mutant was prepared wherein all three cysteine
      residues were replaced by alanine. Surprisingly, while two of the three cysteine
      to serine mutants were inactive, all alanine mutants exhibited near wild-type
      levels of activity, including the triple mutant. These results provide the first
      direct and unambiguous chemical evidence against a covalent cysteine intermediate
      in the rearrangement mechanism of uridine to pseudouridine.

PMID- 8999884
TI  - Identification of the major positive regulators of c-myb expression in
      hematopoietic cells of different lineages.
AB  - The c-myb gene is primarily expressed in hematopoietic cells, and it is
      overexpressed in many leukemias. The regulation of its expression is of critical
      importance in hematopoietic cells. We identified the major positive regulatory
      sites in the 5'-flanking sequence of the human c-myb gene, and we found that the
      positive regulators differed in cells of different lineages. In the Molt-4 T-cell
      line, two Ets-like binding sites were required for the expression of c-myb. The
      5' site played a minor role in the regulation of c-myb expression, and we
      demonstrated that a protein of 67 kDa bound to this site. Antibodies against Ets
      proteins showed no cross-reactivity with this protein. We showed that Ets-1 bound
      to the 3'-regulatory site in the c-myb promoter by electrophoretic mobility shift
      assay and antibody studies. Both of these Ets-like binding sites were
      nonfunctional in the DHL-9 B-cell line and the K562 myeloid cell line. We
      identified a novel transcription factor of 50.5 kDa that was required for
      expression of c-myb in these cell lines.

PMID- 8999886
TI  - Palmitylation of the vaccinia virus 37-kDa major envelope antigen. Identification
      of a conserved acceptor motif and biological relevance.
AB  - Computer-assisted alignment of known palmitylproteins was used to identify a
      potential peptide motif, TMDX1-12AAC(C)A (TMD, transmembrane domain; X, any amino
      acid; C, cysteine acceptor residues; A, aliphatic residue) responsible for
      directing internal palmitylation of the vaccinia virus 37-kDa major envelope
      antigen, p37. Site-directed mutagenesis was used to confirm this motif as the
      site of modification and to produce a nonpalmitylated version of the p37 protein.
      Comparative phenotypic analysis of the wild-type and mutant p37 alleles confirmed
      that the p37 protein is involved in viral envelopment and egress, and suggested
      that attachment of the palmitate moiety was essential for correct intracellular
      targeting and protein function.

PMID- 8999887
TI  - Activation of a CrmA-insensitive, p35-sensitive pathway in ionizing radiation
      induced apoptosis.
AB  - The response of eukaryotic cells to ionizing radiation (IR) includes induction of
      apoptosis. However, the signals that regulate this response are unknown. The
      present studies demonstrate that IR treatment of U-937 cells is associated with:
      (i) internucleosomal DNA fragmentation; (ii) cleavage of poly(ADP-ribose)
      polymerase; (iii) cleavage of protein kinase C delta; and (iv) induction of an Ac
      DEVD-p-nitroanilide cleaving activity. Overexpression of the cowpox protein CrmA
      blocked tumor necrosis factor (TNF)-induced apoptosis but had no effect on IR
      induced DNA fragmentation or cleavage of poly(ADP-ribose) polymerase and protein
      kinase C delta. By contrast, overexpression of the baculovirus p35 protein
      blocked both IR- and TNF-induced apoptosis. The results further demonstrate that
      the IR-induced proteolytic activity is directly inhibited by the addition of
      purified recombinant p35, but not by CrmA. We show that the CPP32 protease is
      sensitive to p35 and not CrmA. We also show that IR induces activation of CPP32
      and that this event, like induction of apoptosis, is sensitive to overexpression
      of p35 and not CrmA. These findings indicate that IR-induced apoptosis involves
      activation of CPP32 and that this CrmA-insensitive apoptotic pathway is distinct
      from those induced by TNF and certain other stimuli.

PMID- 8999888
TI  - The transmembrane domain of a carboxyl-terminal anchored protein determines
      localization to the endoplasmic reticulum.
AB  - UBC6 is a C-terminal membrane-anchored (type IV) protein, native to Saccharomyces
      cerevisiae, where it is found in the endoplasmic reticulum. When expressed in
      mammalian cells, this novel ubiquitin-conjugating enzyme also localizes to the
      endoplasmic reticulum. UBC6 lacks a lumenal domain and contains no known
      endoplasmic reticulum retention signals. Analysis of chimeric proteins in which
      the cytosolic domain of UBC is linked to a heterologous transmembrane domain, or
      in which the UBC6 transmembrane domain is appended to an unrelated soluble
      protein, led to the determination that the transmembrane domain of UBC6 plays a
      dominant role in its compartmental localization. The basis for the transmembrane
      domain-mediated subcellular targeting of UBC6 was evaluated by lengthening the
      wild type UBC6 hydrophobic segment from 17 to 21 amino acids, which resulted in
      re-targeting to the Golgi complex. A further increase in length to 26 amino acids
      allowed this modified protein to traverse the secretory pathway and gain
      expression at the plasma membrane. These findings are consistent with models in
      which, in the absence of dominant cytosolic or lumenal targeting determinants,
      proteins may be sorted within the secretory pathway based on interactions between
      their transmembrane domains and the surrounding lipid bilayer.

PMID- 8999889
TI  - Tissue plasminogen activator (t-PA) is targeted to the regulated secretory
      pathway. Catecholamine storage vesicles as a reservoir for the rapid release of t
      PA.
AB  - Tissue-type plasminogen activator (t-PA) is a serine protease that plays a
      central role in the regulation of intravascular thrombolysis. The acute release
      of t-PA in vivo is induced by a variety of stimuli including exercise, trauma,
      and neural stimulation. These types of stimuli also result in sympathoadrenal
      activation and exocytotic release of amines and proteins from catecholamine
      storage vesicles of the adrenal medulla and sympathetic neurons. Therefore, we
      tested the hypothesis that t-PA is packaged in and released directly from
      catecholamine storage vesicles, using several chromaffin cell sources including
      the rat pheochromocytoma PC-12 chromaffin cell line, primary cultures of bovine
      adrenal chromaffin cells, and human pheochromocytoma. t-PA was expressed in
      chromaffin cells as detected by Northern blotting, immunoprecipitation of
      [35S]Met-labeled t-PA, and specific t-PA enzyme-linked immunosorbent assay of
      cell homogenates. In addition, chromaffin cell t-PA was enzymatically active by
      fibrin zymography. To explore the subcellular localization of the expressed t-PA,
      PC-12 cells were labeled with [3H]norepinephrine, homogenized, and subjected to
      sucrose density fractionation. [3H]Norepinephrine and t-PA antigen were co
      localized to the same subcellular fraction with a major peak at 1.4 M sucrose,
      consistent with the buoyant density of catecholamine storage vesicles. In
      addition, catecholamine storage vesicle lysates isolated from human
      pheochromocytoma tumors were enriched approximately 30-fold in t-PA antigen,
      compared with tumor homogenate. Furthermore, exposure of PC-12 cells or primary
      bovine adrenal chromaffin cells to chromaffin cell secretagogues (60 microM
      nicotine, 55 mM KCl, or 2 mM BaCl2) resulted in co-release of t-PA in parallel
      with catecholamines. These data demonstrate that t-PA is expressed in chromaffin
      cells, is sorted into the regulated pathway of secretion, and is co-released with
      catecholamines by chromaffin cell stimulation. Catecholamine storage vesicles may
      be an important reservoir and sympathoadrenal activation an important physiologic
      mechanism for the rapid release of t-PA. In addition, expression of t-PA by
      chromaffin cells suggests a role for this protease in the proteolytic processing
      of chromaffin cell proteins.

PMID- 8999890
TI  - Discrete cross-linking products identified during membrane protein biosynthesis.
AB  - We have investigated the molecular details of the membrane insertion of the
      multiple-spanning membrane protein opsin. Using heterobifunctional cross-linking
      reagents the endoplasmic reticulum (ER) proteins adjacent to a series of defined
      translocation intermediates were determined. Once the nascent opsin chain reaches
      a critical minimum length Sec61alpha is the major ER component adjacent to the
      polypeptide. Using a homobifunctional reagent, the cross-linking partners from a
      single cysteine residue in the nascent chain were analyzed. This approach
      identified chain length-dependent cross-linking products between nascent opsin
      and a 21-kDa ribosomal protein, followed by Sec61beta and finally with
      Sec61alpha. Our data support a model where the sequential transmembrane domains
      of a multiple-spanning membrane protein are integrated at an ER insertion site
      similar to that mediating the insertion of single-spanning membrane proteins.

PMID- 8999891
TI  - Increased activity of small GTP-binding protein-dependent phospholipase D during
      differentiation in human promyelocytic leukemic HL60 cells.
AB  - In response to dibutyryl cyclic AMP (dbcAMP) and all-trans retinoic acid, human
      promyelocytic leukemic HL60 cells differentiate into granulocyte-like cells. In
      cell lysate and in vitro reconstitution system, phospholipase D (PLD) activity in
      response to guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) was up-regulated by
      dbcAMP or all-trans retinoic acid treatment. In the present study, the
      mechanism(s) for increased PLD activity during differentiation was examined.
      Western blot analysis revealed that the contents of ADP-ribosylation factor,
      Rac2, and Cdc42Hs but not RhoA and Rac1 in the cytosolic fraction were elevated
      during differentiation. However, the cytosolic fraction from undifferentiated
      cells was almost equally potent as the cytosolic fraction from differentiated
      cells in the ability to stimulate membrane PLD activity. It was shown that the
      GTPgammaS-dependent PLD activity in membranes from differentiated cells was much
      higher than that in membranes from undifferentiated cells, suggesting that the
      increased PLD activity during differentiation was due to alterations in some
      membrane component(s). Clostridium botulinum ADP-ribosyltransferase C3 and C.
      difficile toxin B, which are known as inhibitors of RhoA and Rho family proteins,
      respectively, effectively suppressed PLD activity in membranes from
      differentiated cells. In fact, the amount of membrane-associated RhoA was
      increased during differentiation. Furthermore, the extent of GTPgammaS-dependent
      PLD activity partially purified from membranes from differentiated cells was
      greater than that from membranes from undifferentiated cells in the presence of
      recombinant ADP-ribosylation factor 1. The PLD (hPLD1) mRNA level was observed to
      be up-regulated during differentiation, as inferred by reverse transcription
      polymerase chain reaction. Our results suggest the possibility that the increased
      Rho proteins in membranes and the changed level of PLD itself may be, at least in
      part, responsible for the increase in GTPgammaS-dependent PLD activity during
      granulocytic differentiation of HL60 cells.

PMID- 8999892
TI  - Binding of thrombin to the G-protein-linked receptor, and not to glycoprotein Ib,
      precedes thrombin-mediated platelet activation.
AB  - The roles of the G-protein-linked thrombin receptor and platelet glycoprotein Ib
      (GPIb) as alpha-thrombin-binding sites on platelets remain controversial. alpha
      Thrombin has been proposed to bind to both GPIb and the hirudin-like domain of
      the G-protein-linked receptor (from which it cleaves the NH2-terminal
      extracellular domain to release a 41-mer peptide (TR-(1-41), where TR is alpha
      thrombin receptor)) to initiate platelet activation. Using affinity-purified
      rabbit anti-human TR-(1-41) IgG and immunoblotting, we demonstrated TR-(1-41)
      release from platelets suspended in Tyrode's buffer containing 2 mM CaCl2 and
      incubated with >/=0.5 nM alpha-thrombin for 10-60 s at 37 degrees C. As
      quantified by enzyme-linked immunosorbent assay, 0.32-0.59 nM TR-(1-41) was
      released from washed platelets (5 x 10(11) platelets/liter) after their
      incubation with 10 nM alpha-thrombin for 10 s. Parallel binding of alpha-thrombin
      to and activation of the platelets were confirmed by flow cytometry. A monoclonal
      antibody against the hirudin-like domain of the G-protein-linked receptor
      abrogated alpha-thrombin binding to platelets, cleavage of TR-(1-41), and
      platelet activation by </=1.0 nM (but not 10 nM) alpha-thrombin. Proteolysis of
      platelet GPIb with Serratia marcescens protease or O-sialoglycoprotein
      endopeptidase had no effect on alpha-thrombin binding to platelets or their
      subsequent activation. In contrast, chymotrypsin, which cleaves both GPIb and the
      G-protein-linked receptor, abrogated alpha-thrombin binding to platelets, TR-(1
      41) release, and platelet activation. Furthermore, monoclonal antibodies directed
      against the reported alpha-thrombin-binding site on GPIb inhibited neither alpha
      thrombin binding to nor activation of the platelets. Thus, alpha-thrombin binds
      to and cleaves the G-protein-linked receptor when it activates platelets, and
      GPIb does not appear to serve as an important binding site when alpha-thrombin
      activates platelets.

PMID- 8999893
TI  - Oxidation inhibits substrate proteolysis by calpain I but not autolysis.
AB  - In this study, the effects of oxidation on calpain I autolysis and calpain
      mediated proteolysis were examined. Calpain I was incubated with increasing
      concentrations of free calcium in the presence or absence of oxidant, and
      autolytic conversion of both the 80- and 30-kDa subunits was measured by
      immunoblotting utilizing monoclonal antibodies which recognize both autolyzed and
      non-autolyzed forms of each subunit, respectively. Autolytic conversion of the 80
      kDa subunit of calpain I was not detected until free calcium concentration was
      greater than 40 microM, whereas autolysis of the 30-kDa subunit did not occur
      until the free calcium concentration was greater than 100 microM. In addition,
      autolytic conversion of either the 80- or 30-kDa subunit was not inhibited by the
      presence of oxidant. Calpain I activity was measured using the fluorescent
      peptide N-succinyl-L-leucyl-L-leucyl-L-valyl-L-tyrosine-7-amido-4- methylcoumarin
      or the microtubule-associated protein tau as substrate. Calpain I was found to
      have proteolytic activity at free calcium concentrations below that required for
      autolysis. Calpain I activity was strongly inhibited by oxidant at all calcium
      concentrations studied, suggesting that proteolytic activity of both the non
      autolyzed 80-kDa and autolyzed 76-kDa forms was susceptible to oxidation.
      Interestingly, whereas oxidation did not inhibit autolytic conversion, the
      presence of high substrate concentrations did result in a significant reduction
      of autolysis without altering calpain proteolytic activity. Calpain I activity
      that had been inhibited by the presence of oxidant was recovered immediately by
      addition of the reducing agent dithiothreitol.

PMID- 8999894
TI  - Ligand-induced peroxisome proliferator-activated receptor alpha conformational
      change.
AB  - Structurally diverse peroxisome proliferators and related compounds that have
      been demonstrated to induce the ligand-dependent transcriptional activation
      function of mouse peroxisome proliferator-activated receptor alpha (mPPARalpha)
      in transfection experiments were tested for the ability to induce conformational
      changes within mPPARalpha in vitro. WY-14,643, 5,8,11,14-eicosatetraynoic acid,
      LY-171883, and clofibric acid all directly induced mPPARalpha conformational
      changes as evidenced by a differential protease sensitivity assay. Carboxyl
      terminal truncation mutagenesis of mPPARalpha differentially affected the ability
      of these ligands to induce conformational changes suggesting that PPAR ligands
      may make distinct contacts with the receptor. Direct interaction of peroxisome
      proliferators and related compounds with, and the resulting conformational
      alteration(s) in, mPPARalpha may facilitate interaction of the receptor with
      transcriptional intermediary factors and/or the general transcription machinery
      and, thus, may underlie the molecular basis of ligand-dependent transcriptional
      activation mediated by mPPARalpha.

PMID- 8999895
TI  - Direct evidence that involucrin is a major early isopeptide cross-linked
      component of the keratinocyte cornified cell envelope.
AB  - Involucrin was the first protein to be identified as a likely constituent of the
      insoluble cornified cell envelope (CE) of stratified squamous epithelia. However,
      to date, direct isolation from CEs of involucrin cross-linked by way of the
      transglutaminase-induced isopeptide bond has not been reported. We have treated
      human foreskin CEs with methanol/KOH (saponification) to hydrolyze off much of
      the lipids. By immunogold electron microscopy, this exposed large amounts of
      involucrin epitopes as well as of desmoplakin, a desmosomal structural protein.
      About 20% of the total CE protein could be solubilized by proteolytic digestion
      after saponification, of which involucrin was the most abundant. Subsequent amino
      acid sequencing revealed many peptides involving involucrin cross-linked either
      to itself or to a variety of other known CE protein components, including
      cystatin alpha, desmoplakin, elafin, keratins, members of the small proline-rich
      superfamily, loricrin, and unknown proteins related to the desmoplakin family.
      Specific glutamines or lysines of involucrin were used to cross-link the
      different proteins, such as glutamines 495 and 496 to desmoplakin, glutamine 288
      to keratins, and lysines 468, 485, and 508 and glutamines 465 and 489 for
      interchain involucrin cross-links. Many identical peptides were obtained from
      immature CEs isolated from the inner living cell layers of foreskin epidermis.
      The multiple cross-linked partners of involucrin provide experimental
      confirmation that involucrin is an important early scaffold protein in the CE.
      Further, these data suggest that there is significant redundancy in the
      structural organization of the CE.

PMID- 8999896
TI  - Induction of interferon-gamma inducing factor in the adrenal cortex.
AB  - Interferon-gamma inducing factor (IGIF) is a recently identified cytokine also
      called interleukin-1gamma (IL-1gamma) or interleukin-18 (IL-18). Its biological
      activity is pleiotropic, and, so far, it has been shown to induce interferon
      gamma production in Th1 cells, to augment the production of granulocyte
      macrophage-CSF, and to decrease that of interleukin-10 (IL-10). We first detected
      newly synthesized IGIF mRNA by differential display in the adrenal gland of
      reserpine-treated rats and then isolated two transcripts by reverse transcription
      polymerase chain reaction. They were identified as rat IGIF on the basis of the
      high homology with mouse: 91% at both the nucleotide and the amino acid level.
      Subsequently, we investigated the effects of stress on IGIF mRNA levels and found
      that acute cold stress strongly induced IGIF gene expression. In situ
      hybridization analysis showed that IGIF is synthesized in the adrenal cortex,
      specifically in the zona reticularis and fasciculata that produce
      glucocorticoids. The presence of IGIF mRNA was also detected in the
      neurohypophysis although induction by stress was not significant. Our results
      call for more attention to the role of the adrenal gland as a potential effector
      of immunomodulation and suggest that IGIF itself might be a secreted
      neuroimmunomodulator and play an important role in orchestrating the immune
      system following a stressful experience.

PMID- 8999897
TI  - Nontoxic amyloid beta peptide 1-42 suppresses acetylcholine synthesis. Possible
      role in cholinergic dysfunction in Alzheimer's disease.
AB  - We show here that amyloid beta peptide1-42 (Abeta1-42) may play a key role in the
      pathogenesis of the cholinergic dysfunction seen in Alzheimer's disease (AD), in
      addition to its putative role in amyloid plaque formation. Abeta1-42 freshly
      solubilized in water (non-aged Abeta1-42), which was not neurotoxic without
      preaggregation, suppressed acetylcholine (ACh) synthesis in cholinergic neurons
      at very low concentrations (10-100 nM), although non-aged Abeta1-40 was
      ineffective. Non-aged Abeta1-42 impaired pyruvate dehydrogenase (PDH) activity by
      activating mitochondrial tau protein kinase I/glycogen synthase kinase-3beta, as
      we have already shown in hippocampal neurons (Hoshi, M., Takashima, A., Noguchi,
      K., Murayama, M., Sato, M., Kondo, S., Saitoh, Y., Ishiguro, K., Hoshino, T., and
      Imahori, K. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 2719-2723). Neither
      choline acetyltransferase activity nor choline metabolism was affected.
      Therefore, the major cause of reduced ACh synthesis was considered to be an
      inadequate supply of acetyl-CoA owing to PDH impairment. Soluble Abeta1-42
      increases specifically in AD brain (Kuo, Y.-M., Emmerling, M. R., Vigo-Pelfrey,
      C., Kasunic, T. C., Kirkpatrick, J. B., Murdoch, G. H., Ball, M. J., and Roher,
      A. E. (1996) J. Biol. Chem. 271, 4077-4081). This increase in soluble Abeta1-42
      may disturb cholinergic function, leading to the deterioration of memory and
      cognitive function that is characteristic of AD.

PMID- 8999898
TI  - Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved
      in CD30-mediated NFkappaB activation.
AB  - Signals emanated from CD30 can activate the nuclear factor kappaB (NFkappaB). The
      two conserved subdomains, D1 and D2, in the C-terminal cytoplasmic region of CD30
      were tested for interaction with two tumor necrosis factor receptor-associated
      factor (TRAF) proteins with NFkappaB activating capacity, TRAF2 and TRAF5. TRAF5
      is the newest member of the TRAF family that binds to lymphotoxin beta receptor
      and CD40. TRAF5, as well as TRAF2, interacted with the D2 subdomain of CD30 in
      vitro and in vivo. Deletion analysis by the yeast two-hybrid system revealed that
      the C-terminal 22 and 30 amino acid residues are dispensable for interaction of
      TRAF5 and TRAF2 with CD30, respectively. Substitution of alanine for threonine at
      463 abolished the interaction with TRAF2. Overexpression of the TRAF domain of
      TRAF2 or TRAF5 showed a dominant negative effect on CD30-mediated NFkappaB
      activation. Simultaneous expression of these TRAF domains further suppressed the
      NFkappaB activation, suggesting an interplay of these TRAF proteins. Expression
      of TRAF2 and TRAF5 mRNA was demonstrated in T- and B-cell lines that express
      CD30. Taken together, our results indicate that TRAF2 and TRAF5 directly interact
      with CD30 and are involved in NFkappaB activation by CD30 signaling.

PMID- 8999899
TI  - Inhibition of Plasmodium falciparum protein synthesis. Targeting the plastid-like
      organelle with thiostrepton.
AB  - The human malaria parasite Plasmodium falciparum has two extrachromosomal DNAs
      associated with organelles whose function is unclear. Both genomes encode
      ribosomal RNAs (rRNAs) that are distinct from the nuclear-encoded rRNAs.
      Secondary structure analysis of all the P. falciparum rRNAs indicates that only
      the large subunit (LSU) rRNA encoded by the plastid-like genome is the target for
      thiostrepton. Indeed we find that thiostrepton inhibits growth of the parasite in
      the micromolar range which is 10-fold below concentrations with observable
      effects on total protein synthesis. We have further examined selective effects of
      thiostrepton on the plastid function by comparing differential effects of the
      drug on cytoplasmic and organellar encoded transcripts. Treatment with either
      thiostrepton or rifampin, an inhibitor of organellar and eubacterial RNA
      polymerase, both showed disappearance of organellar-encoded RNA transcripts
      within 6 h of treatment while transcripts of a nuclear-encoded mRNA remained
      constant for at least 8 h of treatment. Hence, we show a selective effect on
      organelle function that is suggestive of interference in the protein synthesis
      apparatus of the plastid. Sensitivity of P. falciparum to thiostrepton confirms
      that the plastid-like genome is essential for the erythrocytic cycle and presents
      a novel therapeutic site for this class of antibiotics.

PMID- 8999900
TI  - Prolactin activates tyrosyl phosphorylation of insulin receptor substrate 1 and
      phosphatidylinositol-3-OH kinase.
AB  - Prolactin (PRL) has been demonstrated to induce tyrosine phosphorylation and
      activation of the cytoplasmic tyrosine kinase JAK2. The present study represents
      an initial effort to identify the phosphorylation repertoire of the PRL receptor
      (PRLR). For this purpose we have modified the rat PRLR cDNA to encode an
      additional N-terminal epitope specifically designed to allow the rapid
      purification of the PRLR and associated proteins from transfected cells. The Flag
      tagged PRLR was stably expressed in the human 293 cell line. PRL induced tyrosine
      phosphorylation of proteins of 85, 95, and 185 kDa from 10 to 30 min after PRL
      stimulation. Immunoblot analysis of immunoprecipitation indicates that p85
      corresponds to the 85-kDa regulatory subunit of phosphatidylinositol (PI)-3'
      kinase, p95 to PRLR, and p185 to insulin receptor substrate 1 (IRS-1). Both PI-3'
      kinase and IRS-1 appear to associate with PRLR in a PRL-dependent manner. These
      results thus indicate that kinases other than JAK2, namely PI-3' kinase, are
      activated by PRL.

PMID- 8999901
TI  - FtsY, the prokaryotic signal recognition particle receptor homologue, is
      essential for biogenesis of membrane proteins.
AB  - In mammalian cells, many secretory proteins are targeted to the endoplasmic
      reticulum co-translationally, by the signal recognition particle (SRP) and its
      receptor. In Escherichia coli, the targeting of secretory proteins to the inner
      membrane can be accomplished post-translationally. Unexpectedly, despite this
      variance, E. coli contains essential genes encoding Ffh and FtsY with a
      significant similarity to proteins of the eukaryotic SRP machinery. In this
      study, we investigated the possibility that the prokaryotic SRP-like machinery is
      involved in biogenesis of membrane proteins in E. coli. The data presented here
      demonstrate that the SRP-receptor homologue, FtsY, is indeed essential for
      expression of integral membrane proteins in E. coli, indicating that, in the case
      of this group of proteins, FtsY and the mammalian SRP receptor have similar
      functions.

PMID- 8999902
TI  - Structural determinants for interaction with three different effectors on the G
      protein beta subunit.
AB  - In the yeast two-hybrid system, a 100-residue fragment (beta1A) from the N
      terminus of the beta1 subunit interacts with domains specific to adenylyl cyclase
      2 (AC2), the muscarinic atrial potassium channel (GIRK1), and phospholipase C
      beta2 (PLC-beta2). Based on the crystal structure of the G protein, beta1A is
      composed of an N-terminal alpha helix, a loop, and five beta strands in which the
      C-terminal four beta strands form a beta sheet, the first of seven sheets that
      make up the propeller structure of the beta subunit. A mutant of beta1A (L4P,
      L7P, and L14P), in which the alpha helix was potentially destroyed, interacted
      poorly with the G protein gamma subunit but effectively with domains of AC2,
      GIRK1, and PLC-beta2. In contrast, another mutant of beta1A (S72A, D76A, and
      W82A), in which a network of hydrogen bonds was disrupted, interacted poorly with
      GIRK1 and PLC-beta2 domains, but effectively with the gamma subunit and the AC2
      domain. These results suggest that the proper folding of the first five beta
      strands in the G protein beta subunit is a requirement for appropriately
      positioning residues that interact with GIRK1 and PLC-beta2. Furthermore, since
      mutations that potentially disrupted the folding of these beta strands did not
      affect interaction with AC2, the structural determinants on the G protein beta
      subunit for interaction with various effectors may be different.

PMID- 8999903
TI  - Random mutagenesis of the cAMP chemoattractant receptor, cAR1, of Dictyostelium.
      Mutant classes that cause discrete shifts in agonist affinity and lock the
      receptor in a novel activational intermediate.
AB  - The cAMP chemoattractant receptor, cAR1, of Dictyostelium transduces
      extracellular cAMP signals via G protein-dependent and G protein-independent
      mechanisms. While site-directed mutagenesis studies of G protein-coupled
      receptors have provided a host of information regarding the domains essential for
      various functions, many mechanistic and structural questions remain to be
      resolved. We therefore carried out polymerase chain reaction-mediated random
      mutagenesis over a large part of the cAR1 sequence (from TMIII through the
      proximal part of the cytoplasmic tail). We devised a rapid screen for loss-of
      function mutations based on the essential role of cAR1 in the developmental
      program of Dictyostelium. Although there were an average of two amino acid
      substitutions per receptor, approximately 90% of the mutants were able to
      substitute for wild-type cAR1 when expressed in receptor null cells. About 2%
      were loss-of-function mutants that expressed wild-type levels of receptor
      protein. We used biochemical screens to select about 100 of these mutants and
      chose eight representative mutants for extensive characterization. These fell
      into distinct classes. One class had a conditional defect in cAMP binding that
      was reversed by high salt. Another large class had decreased affinity under all
      conditions. Curiously, the decreases were clustered into three discrete
      intervals. One of the most interesting class of mutants lost all capacity for
      signal transduction but was phosphorylated in response to agonist binding. This
      latter finding suggests that there are at least two activated states of cAR1 that
      can be recognized by different downstream effectors.

PMID- 8999905
TI  - Analog binding properties of insulin receptor mutants. Identification of amino
      acids interacting with the COOH terminus of the B-chain of the insulin molecule.
AB  - Recent studies utilizing alanine scanning mutagenesis have identified a major
      ligand binding domain of the secreted recombinant insulin receptor composed of
      two subdomains, one between amino acids 1 and 120 and the other between amino
      acids 704 and 716. In order to obtain a more detailed characterization of these
      subdomains, we examined the binding of an insulin superanalog, des-(B25-30)-[His
      A8, Asp-B10, Tyr-B25 alpha-carboxamide]insulin, to alanine mutants of the ligand
      binding determinants of these subdomains. cDNAs encoding mutant secreted
      recombinant receptors were transiently expressed in 293 EBNA cells, and the
      binding properties for this analog of the expressed receptors were evaluated. In
      general des-(B25-30)-[His-A8, Asp-B10, Tyr-B25 alpha-carboxamide]insulin binding
      correlated with insulin binding, suggesting that both peptides bound to the
      receptor in a similar manner. Alanine mutations of eight amino acids (Asn15,
      Phe64, Phe705, Glu706, Tyr708, Leu709, Asn711, and Phe714) of the receptor
      produced the most profound decreases in affinity for des-(B25-30)-[His-A8, Asp
      B10, Tyr-B25 alpha-carboxamide]insulin, suggesting that interactions with these
      amino acids contributed the major part of the free energy of the ligand-receptor
      interaction. Mutation of Arg14 and His710 to Ala produced receptors with
      undetectable insulin binding but an affinity for des-(B25-30)-[His-A8, Asp-B10,
      Tyr-B25 alpha-carboxamide]insulin only 8-23-fold less than for native receptor.
      Further analog studies were performed to elucidate this paradox. The receptor
      binding potencies of His-A8 and Asp-B10 insulins for these receptor mutants
      appeared to parallel their relative potencies for native receptor. In contrast
      the receptor binding potency of des-(B25-30)-[Tyr-B25 alpha-carboxamide]insulin
      was disproportionately increased for these mutants when compared with its potency
      for native receptor.

PMID- 8999904
TI  - Random mutagenesis of the cAMP chemoattractant receptor, cAR1, of Dictyostelium.
      Evidence for multiple states of activation.
AB  - cAMP receptor 1 (cAR1) of Dictyostelium couples to the G protein G2 to mediate
      activation of adenylyl and guanylyl cyclases, chemotaxis, and cell aggregation.
      Other cAR1-dependent events, including receptor phosphorylation and influx of
      extracellular Ca2+, do not require G proteins. To further characterize signal
      transduction through cAR1, we performed random mutagenesis of the third
      intracellular loop (24 amino acids), since the corresponding region of other
      seven helix receptors has been implicated in the coupling to G proteins. Mutant
      receptors were expressed in car1(-) cells and were characterized for G protein
      dependent and -independent signal transduction. Our results demonstrate that cAR1
      is remarkably tolerant to amino acid substitutions in the third intracellular
      loop. Of the 21 positions where amino acid substitutions were observed, one or
      more replacements were found that retained full biological function. However,
      certain alterations resulted in receptors with reduced ability to bind cAMP
      and/or transduce signals. There were specific signal transduction mutants that
      could undergo cAMP-dependent cAR1 phosphorylation but were impaired either in
      coupling to G proteins, in G protein-independent Ca2+ influx, or in both
      pathways. In addition, there were general activation mutants that failed to
      restore aggregation to car1(-) cells and displayed severe defects in all signal
      transduction events, including the most robust response, cAMP-dependent cAR1
      phosphorylation. Certain of these mutant phenotypes were obtained in a
      complementary study, where the entire region of cAR1 from the third to the
      seventh transmembrane helices was randomly mutagenized. Considered together,
      these studies indicate that the activation cycle of cAR1 may involve a number of
      distinct receptor intermediates. A model of G protein-dependent and -independent
      signal transduction through cAR1 is discussed.

PMID- 8999906
TI  - Localization of a factor X interactive site in the A1 subunit of factor VIIIa.
AB  - The protein cofactor, factor (F) VIIIa, is required for the efficient conversion
      of the substrate FX to FXa by the serine protease FIXa. The interaction between
      human FVIII (and its constituent subunits) and FX was characterized using a solid
      phase binding assay performed in the absence of phospholipid and FIXa. Saturable
      binding of FX to heterodimeric FVIII, the FVIII heavy chain (contiguous A1-A2
      domains), the FVIIIa-derived A1/A3-C1-C2 dimer, and the isolated A1 subunit was
      observed with estimated Kd values ranging from approximately 1 to 3 microM. The
      interaction of FX with FVIII was inhibited by moderate ionic strength and was
      Ca2+-dependent, consistent with the salt sensitivity observed in a phospholipid
      independent FXa generation assay. Negligible binding to FX was observed for the
      isolated A2 and A3-C1-C2 subunits of FVIIIa, suggesting that the A1 subunit of
      FVIII contains a primary binding site for FX. A synthetic peptide to the COOH
      terminal acidic region of the A1 subunit, designated FVIII337-372, bound FX and
      effectively competed with A1 for FX binding (Ki = approximately 16 microM). Cross
      linking between the FVIII337-372 peptide and the FX heavy chain was observed
      following reaction with 1-ethyl-3-[(diethylamino)propyl]carbodiimide. The
      presence of FX reduced the rate of activated protein C-catalyzed cleavage at
      Arg336 by approximately 5-fold. These results identify a primary FX interactive
      site on the cofactor of the intrinsic FXase.

PMID- 8999907
TI  - Expression of human H-type alpha1,2-fucosyltransferase encoding for blood group
      H(O) antigen in Chinese hamster ovary cells. Evidence for preferential
      fucosylation and truncation of polylactosamine sequences.
AB  - The human H(O) blood group is specified by the structure Fucalpha1-2Galbeta1-R,
      but the factors regulating expression of this determinant on cell surface
      glycoconjugates are not well understood. To learn more about the regulation of H
      blood group expression, cDNA encoding the human H-type GDPFuc:beta-D-galactoside
      alpha1, 2-fucosyltransferase (alpha1,2FT) was stably transfected into Chinese
      hamster ovary (CHO) cells. The new cell line, designated CHO(alpha1,2)FT,
      expressed surface neoglycans containing the H antigen. The structures of the
      fucosylated neoglycans in CHO(alpha1, 2)FT cells and the distribution of these
      glycans on glycoproteins were characterized. Seventeen percent of the [3H]Gal
      labeled glycopeptides from CHO(alpha1,2)FT cells bound to the immobilized H blood
      group-specific lectin Ulex europaeus agglutinin-I (UEA-I), whereas none from
      parental CHO cells bound to the lectin. The glycopeptides from CHO(alpha1,2)FT
      cells binding to UEA-I contained polylactosamine [3Galbeta1-4GlcNAcbeta1-]n with
      the terminal sequence Fucalpha1-2Galbeta1- 4GlcNAc-R. Fucosylation of the
      polylactosamine sequences on complex-type N-glycans in CHO(alpha1, 2)FT cells
      caused a decrease in both sialylation and length of polylactosamine.
      Unexpectedly, only small amounts of terminal fucosylation was found in
      diantennary complex-type N-glycans. The O-glycans and glycolipids were not
      fucosylated by the H-type alpha1, 2FT. Two major high molecular weight
      glycoproteins, one of which was shown to be the lysosome-associated membrane
      glycoprotein LAMP-1, preferentially contained the H-type structure and were bound
      by immobilized UEA-I. These results demonstrate that in CHO cells the expressed H
      type alpha1,2FT does not indiscriminately fucosylate terminal galactosyl residues
      in complex-type N-glycans, but it favors glycans containing polylactosamine and
      dramatically alters their length and sialylation.

PMID- 8999908
TI  - Syk-dependent and -independent signaling cascades in B cells elicited by osmotic
      and oxidative stress.
AB  - It was found that Syk protein-tyrosine kinase is rapidly activated in B cells
      after H2O2 treatment (oxidative stress) or increased extracellular NaCl
      concentration (osmotic stress) as well as in response to B cell receptor
      activation. In this study we examined the involvement of Syk in responses
      elicited by these types of extracellular stress, particularly Ca2+ responses and
      c-Jun amino-terminal kinase (JNK) activation, using a chicken B cell line, DT40,
      as well as the DT40-derived mutant DT40/Syk(-), which does not express Syk.
      Osmotic stress evokes increases in [Ca2+]i by stimulating an extracellular Ca2+
      influx in both DT40 and DT40/Syk(-) cells. In comparison, oxidative stress
      elicits an increase in [Ca2+]i by stimulating both an extracellular Ca2+ influx
      and Ca2+ release from internal stores in DT40 cells, but this Ca2+ response is
      partially abolished in DT40/Syk(-) cells, indicating that the oxidative stress
      induced Ca2+ response is at least partly dependent on Syk. Interestingly, the
      depletion of Ca2+ results in a significantly decreased level of Syk activation in
      DT40 cells stimulated by oxidative but not osmotic stress. Furthermore, JNK is
      activated to different extents by these two types of stress. The extent of JNK
      activation in DT40/Syk(-) cells in response to osmotic stress is comparable to
      that observed in DT40 cells. Intriguingly, oxidative stress-induced JNK
      activation is significantly compromised in DT40/Syk(-) cells. Collectively, these
      results indicate that both the Ca2+ response and JNK activity induced by
      oxidative stress are partly dependent on Syk, whereas those induced by osmotic
      stress are independent of Syk.

PMID- 8999909
TI  - The Fes protein-tyrosine kinase phosphorylates a subset of macrophage proteins
      that are involved in cell adhesion and cell-cell signaling.
AB  - The c-fps/fes proto-oncogene encodes a 92-kDa protein-tyrosine kinase that is
      expressed at high levels in macrophages. We have previously shown that
      overexpression of c-fps/fes in a CSF-1-dependent macrophage cell line (BAC1.2F5)
      partially released these cells from their factor dependence and that this
      correlated with the tyrosine phosphorylation of a subset of proteins in a tissue
      specific manner. We have now identified one of the macrophage substrates of Fes
      as the crk-associated substrate (Cas) and a second substrate as a 130-kDa protein
      that has been previously described as a T cell activation-dependent substrate and
      is unrelated to Cas. Both of these proteins, which have optimal consensus
      sequences for phosphorylation by Fes, were tightly associated with this kinase
      through its SH2 domain, suggesting that they were direct substrates of Fes.
      Remarkably, when the Fes SH2 domain was used as an affinity reagent to identify
      potential substrates of endogenous Fes in control BAC1.2F5 cells, the
      phosphotyrosyl proteins that were recognized were the same as those that were
      specifically phosphorylated when Fes was overexpressed in the same cells. We
      conclude that the substrates we identified may be structurally related or
      identical to the physiological targets of this kinase in macrophages. The known
      functions of Cas and p130 suggest that Fes kinase may play a role in signaling
      triggered by cell adhesion and cell-cell interactions during immune responses of
      macrophages.

PMID- 8999910
TI  - Cation effects on protein conformation and transport in the Na+/glucose
      cotransporter.
AB  - Cation-driven cotransporters are essential membrane proteins in procaryotes and
      eucaryotes, which use the energy of the transmembrane electrochemical gradient to
      drive transport of a substrate against its concentration gradient. Do they share
      a common mechanism? Cation selectivity of the rabbit isoform of the Na+/glucose
      cotransporter (SGLT1) was examined using the twoelectrode voltage clamp and the
      Xenopus oocyte expression system. The effect of H+, Li+, and Na+ on kinetics of
      SGLT1 was compared to the effects of these cations on the bacterial melibiose. In
      SGLT1, substitution of H+ or Li+ for Na+ caused a kinetic penalty in that the
      apparent affinity for sugar (K0.5sugar) decreased by an order of magnitude or
      more (from 0.2 to 30 mM) depending on the membrane potential and cation. The
      effect of the cation on the K0.5sugar/V profiles was independent of the sugar for
      glucose and alpha-methyl-beta-D-glucose; this profile was maintained for
      galactose in Li+ and Na+, but was 2 orders of magnitude higher in H+, but the
      Imax for glucose, galactose, and alpha-methyl-beta-D-glucose in a given cation
      were identical. Li+ supported a lower maximal rate of transport (Imax) than Na+
      (approximately 80% of ImaxNa), while the Imax in H+ was higher than Na+ (>/=180%
      of ImaxNa). Our interpretation of these results and simulations using a six-state
      mathematical model, are as follows. 1) Binding of the cation causes a
      conformational change in the sugar binding pocket, the exact conformation being
      determined by the specific cation. 2) Once the sugar is bound, it is transported
      at a characteristic rate determined by the cation. 3) Mathematical simulations
      suggest that the largest contribution to the kinetic variability of both cation
      and sugar transport is associated with cation binding. Similarity to the effects
      of cation substitution in MelB suggests that the mechanism of energy coupling has
      been evolutionarily conserved.

PMID- 8999911
TI  - Saturation of the endocytic pathway for the transferrin receptor does not affect
      the endocytosis of the epidermal growth factor receptor.
AB  - Cell-surface receptors that undergo clathrin-mediated endocytosis contain short
      amino acid sequences in their cytoplasmic domain that serve as internalization
      signals. Interactions between these sequences and components of the endocytic
      machinery should become limiting upon overexpression of the constitutively
      recycling transferrin receptor (TfR). A tetracycline-responsive system was used
      to induce overexpression of the TfR up to 20-fold in HeLa cells. Internalization
      assays indicate the rate of 125I-transferrin uptake per surface TfR is reduced by
      a factor of 4 in induced cells. Consistent with endocytosis being the rate
      limiting step, TfRs shift from an endosomal to more of a plasma membrane
      distribution with TfR overexpression. The clathrin-associated protein AP-2 has
      been proposed to interact directly with the cytoplasmic domain of many receptors,
      yet no changes in the amount or distribution of AP-2 were detected in induced
      cells. The internalization rate for the epidermal growth factor receptor was also
      measured, with or without induction of TfR expression. Even though endocytosis of
      the TfR is saturated in induced cells, 125I-labeled epidermal growth factor
      continues to be internalized at a rate identical to that seen in uninduced cells.
      We propose that there are different limiting steps for the endocytosis of these
      two receptors.

PMID- 8999913
TI  - Evaluation of secondary structure of OxlT, the oxalate transporter of Oxalobacter
      formigenes, by circular dichroism spectroscopy.
AB  - OxlT, the oxalate/formate exchange transporter of Oxalobacter formigenes, was
      purified as a histidine-tagged variant, OxlTHis, using Ni2+-linked affinity
      chromatography. OxlTHis was readily obtained in high purity (>/=95%) and
      reasonable yield (>/=60%), and showed kinetic and biochemical features
      characteristic of its parent, OxlT, including an unusually high maximal velocity
      (60 micromol/min per mg of protein at 4 degrees C). Circular dichroism
      spectroscopy of purified OxlTHis identified the alpha-helix as its dominant
      secondary structural unit, encompassing 60-70% of OxlTHis residues and consistent
      with a model suggesting 60% of OxlT (OxlTHis) residues are involved in the
      construction of 12 transmembrane alpha-helices (Abe, K., Ruan, Z.-S., and
      Maloney, P. C. (1996) J. Biol. Chem. 271, 6789-6793). In either octyl
      glucoside/lipid or dodecylmaltoside/lipid micelles, solubilized OxlTHis showed a
      striking substrate-induced stabilization of function, and at saturating levels of
      substrate (1000 x KD) activity recoverable by reconstitution disappeared with a
      half-life of 7 days at 23 degrees C. Measurement of changes of ellipticity at 222
      nm as a function of time and substrate concentration showed that maintenance of
      function was attributable to a substrate-induced stabilization of the alpha
      helical ensemble with a KD of 10 microM for the 1:1 binding of oxalate to
      OxlTHis.

PMID- 8999912
TI  - Spectroscopic and kinetic characterization of the recombinant cytochrome c
      reductase fragment of nitrate reductase. Identification of the rate-limiting
      catalytic step.
AB  - The recombinant NADH-cytochrome c reductase fragment of spinach NADH-nitrate
      reductase (EC 1.6.6.1), consisting of the contiguous heme-containing cytochrome b
      domain and flavin-containing NADH-cytochrome b reductase fragment, has been
      characterized spectroscopically and kinetically. Reductive titration with sodium
      dithionite indicates heme reduction takes place prior to flavin reduction, which
      correlates well with the reduction potentials for enzyme-bound heme (15 mV) and
      FAD (-280 mV). Reductive titration with NADH also indicates that the reduced
      enzyme forms a charge-transfer complex with NAD+. The circular dichroism spectrum
      of the oxidized fragment is primarily due to the flavin, whereas the ferrous heme
      dominates the circular dichroism spectrum of reduced enzyme. Three kinetic phases
      are observed in the course of the reaction of the enzyme with NADH, each with a
      distinct spectral signature. The fast phase represents flavin reduction,
      concomitant with the formation of a charge-transfer complex between reduced
      flavin and NAD+, and exhibits hyperbolic dependence on NADH concentration with a
      Kd of 3 microM and a limiting rate constant of 560 s-1. Electron transfer from
      reduced flavin to heme with a rate constant of 12 s-1 is the intermediate phase,
      which is rate-limited by breakdown of the charge-transfer complex between NAD+
      and reduced flavin. The slow phase is dismutation of a pair of molecules of two
      electron reduced enzyme (generated at the end of the second phase of the
      reaction) to give one molecule each of one- and three- electron reduced enzyme,
      with a second order rate constant of 2 x 10(6) M-1 s-1. In the presence of excess
      NADH, this dismutation reaction is followed by the rapid reaction of the one
      electron reduced enzyme with a second equivalent of NADH to generate fully
      reduced enzyme. On the basis of this work, it appears that dissociation of NAD+
      from the reduced flavin site rate limits electron transfer to the cytochrome and
      likely represents the overall rate-limiting step of catalysis.

PMID- 8999914
TI  - Sequential modification of serines 621 and 624 in the Raf-1 carboxyl terminus
      produces alterations in its electrophoretic mobility.
AB  - The Raf-1 serine/threonine protein kinase plays a central role in many of the
      mitogenic signaling pathways regulating cell growth and differentiation. The
      regulation of Raf-1 is complex, and involves protein-protein interactions as well
      as changes in the phosphorylation state of Raf-1 that are accompanied by
      alterations in its electrophoretic mobility. We have previously shown that a 33
      kDa COOH-terminal, kinase-inactive fragment of Raf-1 underwent a mobility shift
      in response to the stimulation of cells with serum or phorbol esters. Here we
      demonstrate that treatment of NIH 3T3 cells or Sf9 cells with hydrogen peroxide
      (H2O2) also induces the mobility shift of the kinase-inactive Raf-1 fragment. A
      series of deletion mutants of the Raf-1 COOH terminus were analyzed, and the
      region required for the mobility shift was localized to a 78-amino acid fragment
      (residues 566-643). Metabolic labeling revealed that the slower migrating forms
      of the 33-kDa and of the smaller fragment contained phosphorus. Mutation of a
      previously characterized phosphorylation site, serine 621, to alanine prevented
      the mobility shift as well as phosphate incorporation or Src and Ras-dependent
      kinase activation in Sf9 cells when this mutation was engineered into the full
      length Raf-1. Mutation of 621 to aspartate yielded a protein that existed in both
      the shifted and unshifted forms, demonstrating that a negative charge at 621 was
      necessary, but not sufficient, for the mobility shift to occur; however, its full
      length form was still resistant to activation in the Sf9 system. Additional
      mutation of nearby serine 624 to alanine blocked the shift, implicating this
      residue as the site of the second of a two-step modification process leading to
      the slower migrating form. Co-expression of the 33-kDa fragment with an activated
      form of mitogen-activated protein kinase kinase in NIH 3T3 led to the appearance
      of the shifted form in a serum-independent manner. These results demonstrate that
      a mitogen-activated protein kinase kinase-induced event involving modification of
      serines 621 and 624 leads to the mobility shift of Raf-1.

PMID- 8999915
TI  - Characterization of the binding of serum amyloid P to laminin.
AB  - Serum amyloid P (SAP) is a member of the pentraxin family. These are
      evolutionarily conserved proteins made up of five noncovalently bound identical
      subunits that are arranged in a flat pentameric disc. Although a variety of
      activities have been attributed to SAP and other pentraxins, their biological
      functions remain unclear. In humans SAP is a constitutive serum protein that is
      synthesized by hepatocytes. It is encoded by a single copy gene on chromosome 1.
      SAP is a component of all amyloid plaques and is also a normal component of a
      number of basement membranes including the glomerular basement membrane. The
      association and distribution of SAP within the glomerular basement membrane are
      altered or completely disrupted in a number of nephritides (e.g. Alport's
      Syndrome, type II membranoproliferative glomerulonephritis, and membranous
      glomerulonephritis). In the present study the binding of SAP to laminin was
      characterized. SAP binds to human laminin and merosin as well as mouse and rat
      laminins. The binding of SAP to mouse laminin is saturable and calcium-dependent.
      The Kd of this interaction is 2. 74 x 10(-7) M, with a SAP/laminin molar ratio of
      1:7.1. Competition binding assays indicate that the binding of SAP to laminin is
      inhibited by both SAP and its analog, C-reactive protein, as well as
      phosphatidylethanolamine. In turbidity assays SAP enhanced the polymerization of
      laminin in a concentration-dependent manner. However, SAP did not alter the
      ability of laminin to serve as a cell adhesion substrate. Previous observations
      indicating that SAP binds to extracellular matrix components such as type IV
      collagen, proteoglycans, and fibronectin in concert with the data presented here
      suggest that SAP may play an important role in determining the structure of those
      basement membranes with which it is associated.

PMID- 8999916
TI  - Biochemical characterization of recombinant fusions of lipopolysaccharide binding
      protein and bactericidal/permeability-increasing protein. Implications in
      biological activity.
AB  - The physiological response to endotoxin (lipopolysaccharide (LPS)) can be
      regulated by two closely related LPS-binding proteins, LPS-binding protein (LBP),
      which potentiates LPS' inflammatory activity via interaction with the monocytic
      antigen CD14, and bactericidal/permeability-increasing protein (BPI), which
      neutralizes LPS. Both proteins bind LPS with high affinity sites in their N
      terminal domains, whereas interaction between LBP and CD14 is dependent upon the
      LBP C-terminal domain. We have created fusions of the N- and C-terminal domains
      from each protein and compared the functional activities and pharmacokinetics of
      these fusions, the individual N-terminal domains, and the parent proteins. The N
      terminal domains of BPI and LBP bound lipid A with their characteristic apparent
      affinity constants, regardless of the C-terminal fusion partner. In addition, the
      C-terminal domain of LBP allowed transfer of LPS to CD14 in conjunction with
      either N-terminal LPS binding domain. Proteins containing a BPI N-terminal domain
      had greater heparin binding capacities in vitro and were cleared more rapidly
      from the plasma of whole animals. Taken together, these data better define how
      closely related proteins such as BPI and LBP can have opposing effects on the
      body's response to LPS.

PMID- 8999917
TI  - Structures of sialylated O-linked oligosaccharides of bovine peripheral nerve
      alpha-dystroglycan. The role of a novel O-mannosyl-type oligosaccharide in the
      binding of alpha-dystroglycan with laminin.
AB  - alpha-Dystroglycan is a heavily glycosylated protein, which is localized on the
      Schwann cell membrane as well as the sarcolemma, and links the transmembrane
      protein beta-dystroglycan to laminin in the extracellular matrix. We have shown
      previously that sialidase treatment, but not N-glycanase treatment, of bovine
      peripheral nerve alpha-dystroglycan greatly reduces its binding activity to
      laminin, suggesting that the sialic acid of O-glycosidically-linked
      oligosaccharides may be essential for this binding. In this report, we analyzed
      the structures of the sialylated O-linked oligosaccharides of bovine peripheral
      nerve alpha-dystroglycan by two methods. O-Glycosidically-linked oligosaccharides
      were liberated by alkaline-borotritide treatment or by mild hydrazinolysis
      followed by 2-aminobenzamide-derivatization. Acidic fractions obtained by anion
      exchange column chromatography that eluted at a position corresponding to
      monosialylated oligosaccharides were converted to neutral oligosaccharides by
      exhaustive sialidase digestion. The sialidases from Arthrobacter ureafaciens and
      from Newcastle disease virus resulted in the same degree of hydrolysis. The
      neutral oligosaccharide fraction, thus obtained, gave a major peak with a
      mobility of 3.8-3.9 glucose units upon gel filtration, and its reducing terminus
      was identified as a mannose derivative. Based on the results of sequential
      exoglycosidase digestion, lectin column chromatography, and reversed-phase high
      performance liquid chromatography, we concluded that the major sialylated O
      glycosidically-linked oligosaccharide of the alpha-dystroglycan was a novel O
      mannosyl-type oligosaccharide, the structure of which was Siaalpha2-3Galbeta1
      4GlcNAcbeta1-2Man-Ser/Thr (where Sia is sialic acid). This oligosaccharide
      constituted at least 66% of the sialylated O-linked sugar chains. Furthermore, a
      laminin binding inhibition study suggested that the sialyl N-acetyllactosamine
      moiety of this sugar chain was involved in the interaction of the alpha
      dystroglycan with laminin.

PMID- 8999918
TI  - "Spot 14" protein functions at the pretranslational level in the regulation of
      hepatic metabolism by thyroid hormone and glucose.
AB  - "Spot 14" protein appears rapidly in nuclei of hepatocytes exposed to glucose and
      thyroid hormone. Exposure of glucose- and T3-treated hepatocytes to a spot 14
      antisense oligonucleotide inhibited induction of mRNAs encoding malic enzyme, ATP
      citrate-lyase, fatty acid synthase, liver-type pyruvate kinase,
      phosphoenolpyruvate carboxykinase, and type I deiodinase but not
      hydroxymethylglutaryl-CoA reductase, cytochrome c, and actin mRNAs. Induction of
      spot 14, ATP citrate-lyase, and fatty acid synthase polypeptides, but not
      propionyl-CoA carboxylase and mitochondrial pyruvate carboxylase, was inhibited.
      Antisense treatment of hepatocytes transfected with a reporter controlled by a
      glucose- and T3-inducible fragment of the pyruvate kinase gene promoter inhibited
      reporter activity, as did cotransfection of the reporter and a spot 14 antisense
      plasmid. Spot 14 protein acts in the induction of mRNAs coding for key lipogenic
      (malic enzyme, ATP citrate-lyase, fatty acid synthase), glycolytic (pyruvate
      kinase), and gluconeogenic enzymes (phosphoenolpyruvate carboxykinase), as well
      as the diet-responsive type I deiodinase, but not those involved in mitochondrial
      respiration (cytochrome c) or cholesterol synthesis (hydroxymethylglutaryl-CoA
      reductase). Transfection experiments indicated that these effects are mediated at
      the transcriptional level. The protein functions in the activation of genes
      involved in metabolic switching between the fasted and fed states in liver.

PMID- 8999919
TI  - Retinoic acid-responsive enhancers located 3' of the Hox A and Hox B homeobox
      gene clusters. Functional analysis.
AB  - Homeobox genes control the spatial identity and differentiation of tissues in the
      developing vertebrate embryo. Retinoids are signaling molecules involved in the
      regulation of Hox genes. We previously identified a 3' enhancer called the
      RAIDR5, which contained a DR5 retinoic acid response element (RARE) and was
      responsible for the retinoic acid (RA)-associated expression of the murine Hoxa-1
      gene in teratocarcinoma cells. We demonstrate that a similar enhancer, which
      contains a DR5 RARE, is located at a DNase I-hypersensitive site 3' of the murine
      Hoxb-1 gene. This enhancer, the Hoxb-1 RAIDR5, regulates the RA responsiveness of
      the Hoxb-1 gene and is different in location and sequence from the RA-regulated
      3' Hoxb-1 enhancers previously described. Several DNA elements within the murine
      Hoxa-1 RA-inducible RAIDR5 enhancer, including the DR5 RARE, conserved element
      (CE) 1, and CE2, are conserved in the murine Hoxb-1 RAIDR5 enhancer, the human
      homolog of Hoxa-1, and in the chicken Hoxb-1 gene. Gel shifts show that the CE2
      sequence TATTTACTCA binds an RA-inducible factor, while UV cross-linking
      indicates that a 170-kDa protein binds to this sequence. Thus, the Hoxa-1 and
      Hoxb-1 genes possess 3' enhancers with similar sequences through which their
      expression and responsiveness to endogenous retinoids are controlled.

PMID- 8999920
TI  - Production and characterization of recombinant human plasminogen(S741C
      fluorescein). A novel approach to study zymogen activation without generation of
      active protease.
AB  - A variant of recombinant plasminogen with the plasmin active site serine (S741)
      replaced by cysteine was produced and labeled with fluorescein at this residue to
      provide the derivative Plg(S741C-fluorescein). Studies of cleavage, conformation,
      and fibrin-binding properties of the derivative showed it to be a good model
      substrate to study plasminogen activation. Both in solution and in a fully
      polymerized fibrin clot, cleavage of the single chain zymogen to the two-chain
      "plasmin" molecule was accompanied by a 50% quench of fluorescence intensity.
      This change allows facile, continuous monitoring of the kinetics of cleavage.
      Measurements of cleavage by single chain t-PA within intact, fully polymerized 3
      microM fibrin yielded apparent kcat and Km values of (0.08 s-1, 0.52 microM) and
      (0.092 s-1, 0.098 microM) for [Glu1]- and [Lys78]Plg(S741C-fluorescein),
      respectively. These values are similar to those obtained by others with plasma
      plasminogen. The approach used here might generally be useful in simplifying the
      analysis of zymogen activation kinetics in cases where the product (protease) has
      a great influence on its own formation via positive or negative feedback loops.

PMID- 8999922
TI  - Serine phospholipid-specific phospholipase A that is secreted from activated
      platelets. A new member of the lipase family.
AB  - Rat platelets secrete two types of phospholipases upon stimulation; one is type
      II phospholipase A2 and the other is serine-phospholipid-selective phospholipase
      A. In the current study we purified serine-phospholipid-selective phospholipase A
      and cloned its cDNA. The final preparation, purified from extracellular medium of
      activated rat platelets, gave a 55-kDa protein band on SDS-polyacrylamide gel
      electrophoresis. [3H]Diisopropyl fluorophosphate, an inhibitor of the enzyme,
      labeled the 55-kDa protein, suggesting that this polypeptide possesses active
      serine residues. The cDNA for the enzyme was cloned from a rat megakaryocyte cDNA
      library. The predicted 456-amino acid sequence contains a putative short N
      terminal signal sequence and a GXSXG sequence, which is a motif of an active
      serine residue of serine esterase. Amino acid sequence homology analysis revealed
      that the enzyme shares about 30% homology with mammalian lipases (lipoprotein
      lipase, hepatic lipase, and pancreatic lipase). Regions surrounding the putative
      active serine, histidine, and aspartic acid, which may form a "lipase triad,"
      were highly conserved among these enzymes. The recombinant protein, which we
      expressed in Sf9 insect cells using the baculovirus system, hydrolyzed a fatty
      acyl residue at the sn-1 position of lysophosphatidylserine and
      phosphatidylserine, but did not appreciably hydrolyze phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid, and
      triglyceride. The present enzyme, named phosphatidylserine-phospholipase A1, is
      the first phospholipase that exclusively hydrolyses the sn-1 position and has a
      strict head group specificity for the substrate.

PMID- 8999923
TI  - Functional characterization of an epidermal growth factor receptor/RET chimera.
AB  - The RET (recombined in transfection) gene encodes a receptor tyrosine kinase
      homolog involved in innervation of the gut and renal development. A chimeric
      epidermal growth factor receptor (EGFR)/RET receptor was constructed which
      contained the extracellular and transmembrane domains of the EGF receptor fused
      to the intracellular domain of RET. This construct was expressed in NIH 3T3
      cells, and the functional properties of the receptor were characterized and
      compared with those of the wild type EGF receptor. Whereas the EGF receptor
      exhibited both high and low affinity binding sites for 125I-EGF, the EGFR/RET
      chimera exhibited only low affinity binding of 125I-EGF. The chimera was able to
      internalize EGF more rapidly than the wild type EGF receptor and recycled to the
      cell surface at twice the rate of the EGF receptor. Pulse-chase experiments
      indicated that EGF stimulated the degradation of the wild type EGF receptor but
      had no effect on the rate of degradation of the EGFR/RET receptor. The
      combination of increased recycling and decreased degradation resulted in the
      relatively inefficient down-regulation of the EGFR/RET chimera. Incubation of
      cells expressing the wild type EGF receptor with phorbol 12-myristate 13-acetate
      led to a reduction in 125I-EGF binding and a loss in EGF-stimulated tyrosine
      phosphorylation. However, phorbol 12-myristate 13-acetate treatment had only a
      limited effect on EGF binding and EGF-stimulated tyrosine kinase activity in
      cells expressing EGFR/RET chimeras. These findings suggest that the ret tyrosine
      kinase is not regulated by many of the common mechanisms used to terminate
      signaling via growth factor receptors. Such persistent activation of the Ret
      tyrosine kinase may be relevant to the physiological function of Ret in cells
      that normally express this growth factor receptor.

PMID- 8999924
TI  - Function of the novel subdomain in the RNA binding domain of transcription
      termination factor Rho from Micrococcus luteus.
AB  - Transcription termination factor Rho from Micrococcus luteus, a high G + C Gram
      positive bacterium, contains an unusual extra sequence within its RNA binding
      domain that is rich in Arg, Glu, and Asp residues and deficient in hydrophobic
      residues. To determine the role of this extra sequence, we compared the
      biochemical properties of a variant lacking nearly all the extra sequence, des(60
      300) Rho, to that of wild-type M. luteus Rho. The two forms had very similar
      properties except that the des(60-300) Rho was unable to terminate transcription
      with Escherichia coli RNA polymerase at the promoter proximal sites used by the
      wild-type Rho on a lambda cro DNA template but could cause termination at more
      distal sites and did cause termination at proximal sites when ITP replaced GTP in
      the reaction mixture. The RNA binding properties of the two forms of this Rho
      with normal and inosine-substituted RNAs were found to correlate fully with their
      termination properties. These results indicate that the arginine-rich extra
      sequence is directly involved in the selection of the termination site and
      support the hypothesis that the sequence is present in M. luteus Rho to
      facilitate its binding to M. luteus transcripts, which are likely to have a high
      degree of base-paired secondary structure because of their high proportion of G
      residues.

PMID- 8999925
TI  - Two-step processing is not essential for the import and assembly of functionally
      active iron-sulfur protein into the cytochrome bc1 complex in Saccharomyces
      cerevisiae.
AB  - The iron-sulfur protein of the cytochrome bc1 complex is one of a small number of
      proteins that are processed in two sequential steps by matrix processing
      peptidase (MPP) and mitochondrial intermediate peptidase (MIP) during import into
      Saccharomyces cerevisiae mitochondria. To test whether two-step processing is
      necessary for import and assembly of the iron-sulfur protein into the cytochrome
      bc1 complex, we mutagenized the presequence of the iron-sulfur protein to
      eliminate the original MPP site and replace the MIP site with a new MPP site. The
      mutated presequence is cleaved and forms mature-sized protein in a single step,
      and the mature-sized iron-sulfur protein is correctly targeted to the outer side
      of the inner mitochondrial membrane in vitro. Mutant iron-sulfur protein which is
      processed to mature size in one step complements the respiratory deficient
      phenotype of a yeast strain in which the endogenous gene for the iron-sulfur
      protein is deleted. These results establish that mature-sized iron-sulfur protein
      can be formed by single-step processing and assembled into a functionally active
      form in the cytochrome bc1 complex in S. cerevisiae.

PMID- 8999926
TI  - Switch of coenzyme specificity of mouse lung carbonyl reductase by substitution
      of threonine 38 with aspartic acid.
AB  - Mouse lung carbonyl reductase, a member of the short-chain
      dehydrogenase/reductase (SDR) family, exhibits coenzyme specificity for NADP(H)
      over NAD(H). Crystal structure of the enzyme-NADPH complex shows that Thr-38
      interacts with the 2'-phosphate of NADPH and occupies the position spatially
      similar to an Asp residue of the NAD(H)-dependent SDRs that hydrogen-bonds to the
      hydroxyl groups of the adenine ribose of the coenzymes. Using site-directed
      mutagenesis, we constructed a mutant mouse lung carbonyl reductase in which Thr
      38 was replaced by Asp (T38D), and we compared kinetic properties of the mutant
      and wild-type enzymes in both forward and reverse reactions. The mutation
      resulted in increases of more than 200-fold in the Km values for NADP(H) and
      decreases of more than 7-fold in those for NAD(H), but few changes in the Km
      values for substrates or in the kcat values of the reactions. NAD(H) provided
      maximal protection against thermal and urea denaturation of T38D, in contrast to
      the effective protection by NADP(H) for the wild-type enzyme. Thus, the single
      mutation converted the coenzyme specificity from NADP(H) to NAD(H). Calculation
      of free energy changes showed that the 2'-phosphate of NADP(H) contributes to its
      interaction with the wild-type enzyme. Changing Thr-38 to Asp destabilized the
      binding energies of NADP(H) by 3.9-4.5 kcal/mol and stabilized those of NAD(H) by
      1.2-1.4 kcal/mol. These results indicate a significant role of Thr-38 in NADP(H)
      binding for the mouse lung enzyme and provide further evidence for the key role
      of Asp at this position in NAD(H) specificity of the SDR family proteins.

PMID- 8999927
TI  - Reconstitution of receptors and GTP-binding regulatory proteins (G proteins) in
      Sf9 cells. A direct evaluation of selectivity in receptor.G protein coupling.
AB  - The selectivity in coupling of various receptors to GTP-binding regulatory
      proteins (G proteins) was examined directly by a novel assay entailing the use of
      proteins overexpressed in Spodoptera frugiperda (Sf9) cells. Activation of G
      proteins was monitored in membranes prepared from Sf9 cells co-expressing
      selected pairs of receptors and G proteins (i.e. alpha, beta1, and gamma2
      subunits). Membranes were incubated with [35S]guanosine 5'-(3-O-thio)triphosphate
      (GTPgammaS) +/- an agonist, and the amount of radiolabel bound to the alpha
      subunit was quantitated following immunoprecipitation. When expressed without
      receptor (but with beta1gamma2), the G protein subunits alphaz, alpha12, and
      alpha13 did not bind appreciable levels of [35S]GTPgammaS, consistent with a
      minimal level of GDP/[35S]GTPgammaS exchange. In contrast, the subunits alphas
      and alphaq bound measurable levels of the nucleotide. Co-expression of the 5
      hydroxytryptamine1A (5-HT1A) receptor promoted binding of [35S]GTPgammaS to
      alphaz but not to alpha12, alpha13, or alphas. Binding to alphaz was enhanced by
      inclusion of serotonin in the assay. Agonist activation of both thrombin and
      neurokinin-1 receptors promoted a modest increase in [35S]GTPgammaS binding to
      alphaz and more robust increases in binding to alphaq, alpha12, and alpha13.
      Binding of [35S]GTPgammaS to alphas was strongly enhanced only by the activated
      beta1-adrenergic receptor. Our data identify interactions of receptors and G
      proteins directly, without resort to measurements of effector activity, confirm
      the coupling of the 5-HT1A receptor to Gz and extend the list of receptors that
      interact with this unique G protein to the receptors for thrombin and substance
      P, imply constitutive activity for the 5-HT1A receptor, and demonstrate for the
      first time that the cloned receptors for thrombin and substance P activate G12
      and G13.

PMID- 8999928
TI  - Characterization of functional domains of the eukaryotic co-chaperone Hip.
AB  - The homo-oligomeric Hip protein cooperates with the 70-kDa heat shock cognate
      Hsc70 in the folding of newly synthesized polypeptide chains and in the
      conformational regulation of signaling molecules known to interact with Hsc70 and
      Hsp90. In order to further assess the role of Hip during protein biogenesis, a
      structure-function analysis of the Hip protein was initiated. By employing the
      yeast two-hybrid system, the Hsc70-binding site of Hip was mapped to a domain
      comprising multiple tetratricopeptide repeats and flanking charged alpha-helices.
      Affinity chromatography confirmed direct interaction of isolated Hip fragments
      and protein fusions bearing this region with the ATPase domain of Hsc70 in an ATP
      and salt-dependent manner. Contact of Hip with the ATPase domain appears to be
      mediated primarily by the positively charged alpha-helix following the
      tetratricopeptide repeats. Furthermore, a domain required for homo
      oligomerization was identified at the extreme amino terminus of Hip.

PMID- 8999929
TI  - Platelet-derived growth factor-stimulated secretion of basement membrane proteins
      by skeletal muscle occurs by tyrosine kinase-dependent and -independent pathways.
AB  - The basement membrane of skeletal muscle is produced by the muscle cells it
      ensheathes and by nonmuscle cells located in the surrounding extracellular
      matrix. In this study, we have shown that platelet-derived growth factor (PDGF)
      stimulates secretion of three basement membrane components of skeletal muscle:
      laminin (70% increase), fibronectin (30%), and type IV collagen (70%).
      Furthermore, we have found using the signal transduction inhibitors, genistein
      (tyrosine kinase inhibitor), phorbol 12-myristate 13-acetate (protein kinase C
      (PKC) inhibitor), thapsigargin (depletes intracellular Ca2+ stores), and H89
      (protein kinase A inhibitor), that PDGF-stimulated secretion of these proteins
      occurs through distinct signaling pathways. Densitometry of Western blots of L6
      myoblast supernatant indicates that the PDGF-induced increase in secretion of
      laminin and type IV collagen is tyrosine kinase-dependent. The increase in type
      IV collagen secretion also shows dependence on PKC, as well as the release of
      intracellular Ca2+. Inhibition of either of these pathways reduces the increase
      in type IV collagen secretion to 20%. In contrast, the PDGF-induced increase in
      laminin secretion is unaffected by inhibition of either PKC or intracellular Ca2+
      release. The increase in fibronectin secretion by PDGF uses yet a third set of
      signals. PDGF-induced fibronectin secretion is not dependent on tyrosine kinase
      activity but is dependent on protein kinase A as well as the release of
      intracellular Ca2+. These divergent signaling pathways provide for independent
      regulation of basement membrane protein secretion, allowing a muscle cell to
      modify both the quantity and composition of its basement membrane in response to
      its environment.

PMID- 8999930
TI  - Heparanases produce distinct populations of heparan sulfate glycosaminoglycans in
      Chinese hamster ovary cells.
AB  - Once internalized, cell-associated heparan sulfate proteoglycans are degraded to
      short glycosaminoglycans by the action of endoglycosidases or heparanases. We
      have begun to address the question of how many heparanases are responsible for
      this process by analyzing short heparan sulfate chains produced in vivo by
      Chinese hamster ovary (CHO) cell heparanases. Short heparan sulfate chains were
      purified from CHO cells and labeled at the reducing end with [3H]NaBH4.
      Hydrolysis of the chains to monosaccharides and analysis of the 3H-sugar alcohols
      indicate that heparanase activities in CHO cells are endo-beta-glucuronidases.
      The modification state of the heparanase-derived glycosaminoglycans was examined
      by treating the [3H]heparan sulfate chains with nitrous acid or bacterial heparin
      lyases, which cut the chain at specific sequences, and analyzing the products by
      P2 gel filtration chromatography. Two populations of short chains were identified
      that differ in the extent of modification on the nonreducing side of the
      heparanase cleavage site. One class of chains is unmodified for at least 9
      residues from the reducing end, while the other group has a modified domain
      within 3-7 residues from the heparanase cleavage site. Our results suggest a
      model of heparanase action where the enzymes recognize differences in sulfate
      content between modified and unmodified regions and bind to sites that encompass
      both domains. The enzymes then cleave the glycosaminoglycan at junctions between
      the modified and unmodified sequences to produce the different populations of
      short heparan sulfate chains.

PMID- 8999931
TI  - Mechanistic studies of R67 dihydrofolate reductase. Effects of pH and an H62C
      mutation.
AB  - R67 dihydrofolate reductase (DHFR) is encoded by an R-plasmid, and expression of
      this enzyme in bacteria confers resistance to the antibacterial drug,
      trimethoprim. This DHFR variant is not homologous in either sequence or structure
      with chromosomal DHFRs. The crystal structure of tetrameric R67 DHFR indicates a
      single active site pore that traverses the length of the molecule (Narayana, N.,
      Matthews, D. A., Howell, E. E., and Xuong, N.-H. (1995) Nat. Struct. Biol. 2,
      1018-1025). A pH profile of enzyme activity in R67 DHFR displays an acidic pKa
      that is protein concentration-dependent. This pKa describes dissociation of
      active tetramer into two relatively inactive dimers upon protonation of His-62
      and the symmetry-related His-162, His-262, and His-362 residues at the dimer
      dimer interfaces. Construction of an H62C mutation results in stabilization of
      the active tetramer via disulfide bond formation at the dimer-dimer interfaces.
      The oxidized, tetrameric form of H62C R67 DHFR is quite active at pH 7, and a pH
      profile displays increasing activity at low pH. These results indicate protonated
      dihydrofolate (pKa = 2.59) is the productive substrate and that R67 DHFR does not
      possess a proton donor.

PMID- 8999932
TI  - Influence of Mg2+ and temperature on formation of the transcription bubble.
AB  - The transcription bubble formed in the binding complex of T7A1 promoter upon
      Escherichia coli RNA polymerase was analyzed by chemical probes, namely by single
      strand specific reagents, to map the unpaired bases in the bubble, and by FeEDTA,
      to analyze the accessibility of the DNA backbone. The latter probe could also be
      used as a local hydroxyl radical probe placed close to the Mg2+-binding site in
      the active center. The data show that the transcription bubble consists of two
      parts, an Mg2+-dependent part and an Mg2+-independent part, both having
      individual transition temperatures. The data further suggest that formation of a
      transcription active open complex is preceded by a transition state complex
      having enhanced affinity for those Mg2+ ions presumably participating in the
      formation of the catalytic site. Our data also suggests that the three
      catalytically active Mg2+ ions in RNA polymerase are functionally not equivalent.
      One/two of the three Mg2+ ions are responsible for the polymerization, the other
      two/one for enlargement of the transcription bubble.

PMID- 8999933
TI  - Sequence analysis of betaA3, betaB3, and betaA4 crystallins completes the
      identification of the major proteins in young human lens.
AB  - A combination of Edman sequence analysis and mass spectrometry identified the
      major proteins of the young human lens as alphaA, alphaB, betaA1, betaA3, betaA4,
      betaB1, betaB2, betaB3, gammaS, gammaC, and gammaD-crystallins and mapped their
      positions on two-dimensional electrophoretic gels. The primary structures of
      human betaA1, betaA3, betaA4, and betaB3-crystallin subunits were predicted by
      determining cDNA sequences. Mass spectrometric analyses of each intact protein as
      well as the peptides from trypsin-digested proteins confirmed the predicted amino
      acid sequences and detected a partially degraded form of betaA3/A1 missing either
      22 or 4 amino acid residues from its N-terminal extension. These studies were a
      prerequisite for future studies to determine how human lens proteins are altered
      during aging and cataract formation.

PMID- 8999935
TI  - Properties of the inositol 3,4,5,6-tetrakisphosphate 1-kinase purified from rat
      liver. Regulation of enzyme activity by inositol 1,3,4-trisphosphate.
AB  - Inositol 3,4,5,6-tetrakisphosphate is a novel intracellular signal that regulates
      calcium-dependent chloride conductance (Xie, W., Kaetzel, M. A., Bruzik, K. S.,
      Dedman, J. R., Shears, S. B., and Nelson, D. J. (1996) J. Biol. Chem. 271, 14092
      14097). The molecular mechanisms that regulate the cellular levels of this signal
      are not characterized. To pursue this problem we have now studied the 1-kinase
      that deactivates inositol 3,4,5,6-tetrakisphosphate. The enzyme was purified from
      rat liver 1600-fold with a 1% yield. The native molecular mass was determined to
      be 46 kDa by gel filtration. The Km values for inositol 3,4,5,6-tetrakisphosphate
      and ATP were 0. 3 and 10.6 microM, respectively. The kinase was unaffected by
      either protein kinase A or protein kinase C. Increases in Ca2+ concentration from
      0.1 to 1-2 microM inhibited activity by 10-20%. Most importantly, inositol 1,3,4
      trisphosphate was shown to be a potent (Ki = 0.2 microM), specific, and
      competitive inhibitor of the 1-kinase. Our new kinetic data show that typical
      receptor-dependent adjustments in cellular levels of inositol 1,3,4-trisphosphate
      provide a mechanism by which the concentration of inositol 3,4,5,6
      tetrakisphosphate is dependent on changes in phospholipase C activity. These
      conclusions also provide a new perspective to our understanding of the
      physiological importance of the pathway of inositol phosphate turnover initiated
      by the inositol 1,4, 5-trisphosphate 3-kinase.

PMID- 8999934
TI  - Identification of lysine 74 in the pyruvate binding site of alanine dehydrogenase
      from Bacillus subtilis. Chemical modification with 2,4,6-trinitrobenzenesulfonic
      acid, n-succinimidyl 3-(2-pyridyldithio)propionate, and 5'-(p
      (fluorosulfonyl)benzoyl)adenosine.
AB  - L-Alanine dehydrogenase from Bacillus subtilis was inactivated with two different
      lysine-directed chemical reagents, i.e. 2,4, 6-trinitrobenzenesulfonic acid and N
      succinimidyl 3-(2-pyridyldithio)propionate. In both cases, the inactivation
      followed pseudo first-order kinetics, with a 1:1 stoichiometric ratio between the
      reagent and the enzyme subunits. Partial protection of the active site from
      inactivation could be obtained by each of the substrates, NADH or pyruvate, but
      complete protection could only be achieved in the presence of the ternary complex
      E.NADH. pyruvate. The nucleotide analogue of NADH, 5'-(p
      (fluorosulfonyl)benzoyl)adenosine was also used for affinity labeling of the
      enzyme active site. Differential peptide mapping, performed both in the presence
      and in the absence of the substrates, followed by reversed phase high performance
      liquid chromatography separation, diode-array analysis, mass spectrometry, and N
      terminal sequencing of the resulting peptides, allowed the identification of
      lysine 74 in the active site of the enzyme. This residue, which is conserved
      among all L-alanine dehydrogenases, is most likely the residue previously
      postulated to be necessary for the binding of pyruvate in the active site.
      Surprisingly, this residue and the surrounding conserved residues are not found
      in amino acid dehydrogenases like glutamate, leucine, phenylalanine, or valine
      dehydrogenases, suggesting that A-stereospecific amino acid dehydrogenases such
      as L-alanine dehydrogenase could have evolved apart from the B-stereospecific
      amino acid dehydrogenases.

PMID- 8999936
TI  - Determination of the solution structures of conantokin-G and conantokin-T by CD
      and NMR spectroscopy.
AB  - Conantokin-G and conantokin-T are two paralytic polypeptide toxins originally
      isolated from the venom of the fish-hunting cone snails of the genus Conus.
      Conantokin-G and conantokin-T are the only naturally occurring peptidic compounds
      which possess N-methyl-D-aspartate receptor antagonist activity, produced by a
      selective non-competitive antagonism of polyamine responses. They are also
      structurally unusual in that they contain a disproportionately large number of
      acid labile post-translational gamma-carboxyglutamic acid (Gla) residues.
      Although no precise structural information has previously been published for
      these peptides, early spectroscopic measurements have indicated that both
      conantokin-G and conantokin-T form alpha-helical structures, although there is
      some debate whether the presence of calcium ions is required for these peptides
      to adopt this fold. We now report a detailed structural study of synthetic
      conantokin-G and conantokin-T in a range of solution conditions using CD and 1H
      NMR spectroscopy. The three-dimensional structures of conantokin-T and conantokin
      G were calculated from 1H NMR-derived distance and dihedral restraints. Both
      conantokins were found to contain a mixture of alpha- and 310 helix, that give
      rise to curved and straight helical conformers. Conantokin-G requires the
      presence of divalent cations (Zn2+, Ca2+, Cu2+, or Mg2+) to form a stable alpha
      helix, while conantokin-T adopts a stable alpha-helical structure in aqueous
      conditions, in the presence or absence of divalent cations (Zn2+, Ca2+, Cu2+, or
      Mg2+).

PMID- 8999937
TI  - Energy coupling, turnover, and stability of the F0F1 ATP synthase are dependent
      on the energy of interaction between gamma and beta subunits.
AB  - Replacement of the F0F1 ATP synthase gamma subunit Met-23 with Lys (gammaM23K)
      perturbs coupling efficiency between transport and catalysis (Shin, K., Nakamoto,
      R. K., Maeda, M., and Futai, M. (1992) J. Biol. Chem. 267, 20835-20839). We
      demonstrate here that the gammaM23K mutation causes altered interactions between
      subunits. Binding of delta or epsilon subunits stabilizes the alpha3beta3gamma
      complex, which becomes destabilized by the mutation. Significantly, the
      inhibition of F1 ATP hydrolysis by the epsilon subunit is no longer relieved when
      the gammaM23K mutant F1 is bound to F0. Steady state Arrhenius analysis reveals
      that the gammaM23K enzyme has increased activation energies for the catalytic
      transition state. These results suggest that the mutation causes the formation of
      additional bonds within the enzyme that must be broken in order to achieve the
      transition state. Based on the x-ray crystallographic structure of Abrahams et
      al. (Abrahams, J. P., Leslie, A. G. W., Lutter, R., and Walker, J. E. (1994)
      Nature 370, 621-628), the additional bond is likely due to gammaM23K forming an
      ionized hydrogen bond with one of the betaGlu-381 residues. Two second site
      mutations, gammaQ269R and gammaR242C, suppress the effects of gammaM23K and
      decrease activation energies for the gammaM23K enzyme. We conclude that gammaM23K
      is an added function mutation that increases the energy of interaction between
      gamma and beta subunits. The additional interaction perturbs transmission of
      conformational information such that epsilon inhibition of ATPase activity is not
      relieved and coupling efficiency is lowered.

PMID- 8999938
TI  - Preferential binding of poly(A)-binding protein 1 to an inhibitory RNA element in
      the human immunodeficiency virus type 1 gag mRNA.
AB  - Human immunodeficiency virus type 1 (HIV-1) mRNAs encoding structural proteins
      contain multiple inhibitory/instability elements (INS), which decrease the
      efficiency of viral protein expression. We have previously identified a strong
      INS element (INS-1) within the p17(gag) coding region. Here we show that poly(A)
      binding protein 1 (PABP1) binds preferentially to INS-1 within the p17(gag) mRNA,
      but not to a mutated mRNA in which INS-1 function is eliminated. Competition
      experiments performed in the presence of different nucleic acids and
      homoribopolymers demonstrated preferential binding of PABP1 to the INS-1
      containing RNA. In contrast to HeLa cells and several lymphoid cell lines,
      certain human glioma cell lines exhibit high levels of gag expression in the
      absence of Rev upon transient transfection with wild type gag expression vectors.
      We analyzed extracts of different cell lines and found that the binding of PABP1
      to INS-1 RNA is significantly diminished in glial cell extracts. The expression
      levels of gag correlate with the absence of binding of PABP1 to the INS-1 RNA in
      cellular extracts. These results suggest a role for PABP1 in the inhibition of
      gag expression mediated through INS-1.

PMID- 8999939
TI  - Structure-function studies of interleukin 15 using site-specific mutagenesis,
      polyethylene glycol conjugation, and homology modeling.
AB  - Interleukin (IL)-15 is a multifunctional cytokine that shares many biological
      activities with IL-2. This functional overlap, as well as receptor binding
      subunits shared by IL-15 and IL-2, suggests tertiary structural similarities
      between these two cytokines. In this study, recombinant human IL-15 was PEGylated
      via lysine-specific conjugation chemistry in order to extend the circulation half
      life of this cytokine. Although PEGylation did extend the beta-elimination
      circulation half-life of IL-15 by greater than 50-fold, the biological activity
      of polyethylene glycol (PEG)-IL-15 was significantly altered. Specifically, PEG
      IL-15 lost its ability to stimulate the proliferation of CTLL but took on the
      properties of a specific IL-15 antagonist in vitro. In comparing sequence
      alignments and molecular models for IL-2 and IL-15, it was noted that lysine
      residues resided in regions of IL-15 that may have selectively disrupted receptor
      subunit binding. We hypothesized that PEGylation of IL-15 interferes with beta
      but not alpha receptor subunit binding, resulting in the IL-15 antagonist
      activity observed in vitro. The validity of this hypothesis was tested by
      engineering site-specific mutants of human IL-15 as suggested by the IL-15 model
      (IL-15D8S and IL-15Q108S block beta and gamma receptor subunit binding,
      respectively). As with PEG-IL-15, these mutants were unable to stimulate CTLL
      proliferation but were able to specifically inhibit the proliferation of CTLL in
      response to unmodified IL-15. These results supported our model of IL-15 and
      confirmed that interference of beta receptor subunit binding by adjacent
      PEGylation could be responsible for the altered biological activity observed for
      PEG-IL-15.

PMID- 8999940
TI  - Activation of 12-O-tetradecanoylphorbol-13-acetate response element- and dyad
      symmetry element-dependent transcription by interleukin-5 is mediated by Jun N
      terminal kinase/stress-activated protein kinase kinases.
AB  - Interleukin-5 (IL-5) is one of the major regulators of eosinophilic granulocytes
      in vivo. IL-5 exerts its pleiotropic effects by binding to the IL-5 receptor,
      which is composed of an IL-5-specific alpha chain and a common betac chain shared
      with the receptors for IL-3 and granulocyte-macrophage colony-stimulating factor.
      Previous studies have shown that binding of IL-5 to its receptor triggers the
      activation of multiple signaling cascades, including the Ras/mitogen-activated
      protein kinase, the phosphatidyl -3'-kinase, and the Janus kinase/signal
      transducer and activator of transcription pathways. Here we describe that IL-5
      activates the serine/threonine protein kinase Jun N-terminal kinase/stress
      activated protein kinase (JNK/SAPK) pathway. We show that IL-5 activates TPA
      response element (TRE)-dependent transcription in transfection experiments. TRE
      activation by IL-5 is mediated by a region of the betac (577-581) that is also
      responsible for activation of JNK/SAPK and for activation of dyad symmetry
      element (DSE)-dependent transcription. Dominant-negative SAPK or ERK kinase-1 was
      used to demonstrate that JNK/SAPK activation is necessary for induction of DSE-
      and TRE-dependent transcription by IL-5, whereas extracellular signal-regulated
      kinase 2 was not essential for TRE- and DSE-dependent transcription. By contrast,
      IL-5-induced activation of the tyrosine kinase Janus kinase 2 seems to be a
      prerequisite for TRE- and DSE-dependent transcription. Taken together, we show
      for the first time that IL-5 activates kinases of the JNK/SAPK family, and that
      this activation is linked to IL-5-induced TRE- and DSE-dependent transcription.

PMID- 8999941
TI  - A receptor-G protein coupling-independent step in the internalization of the
      thyrotropin-releasing hormone receptor.
AB  - To determine whether functional receptor-G protein coupling or signaling are
      required for internalization of the thyrotropin-releasing hormone receptor
      (TRHR), we compared the endocytosis of Gq-coupled and uncoupled receptors. A
      hemagglutinin epitope-tagged TRHR (HA-TRHR) was in the Gq-coupled state when
      bound to the agonist, MeTRH, and in a nonsignaling state when bound to the HA
      antibody (12CA5). 12CA5 did not induce an increase in [Ca2+]i or inositol
      phosphates and did not inhibit [3H]MeTRH binding or MeTRH-induced production of
      second messengers. Both agonist- and antibody-bound HA-TRHRs were rapidly
      internalized via the same pathway; internalization was sensitive to hypertonic
      shock, and both types of internalized receptors were sorted into lysosomes. In
      addition, the amino acid sequence CNC (positions 335-337) in the C-terminal tail
      of the TRHR, which is important in ligand-induced receptor internalization as
      determined by deletion mutagenesis (Nussenzveig, D. R., Heinflink, M., and
      Gershengorn, M. C. (1993) J. Biol. Chem. 268, 2389-2392), was also important for
      12CA5-induced internalization. We expressed two truncated receptors, HA-K338STOP
      and HA-C335STOP, in GH12C1 pituitary cells. Both HA-TRHR and HA-K338STOP were
      localized at the plasma membrane of untreated cells and were translocated to
      intracellular vesicles after MeTRH or 12CA5 binding; however, HA-C335STOP was
      internalized and recycled constitutively. The intracellular localization of HA
      C335STOP was not altered by MeTRH; however, 12CA5 binding induced the
      disappearance of internalized HA-C335STOP and caused its localization at the
      plasma membrane, indicating that constitutively cycling HA-C335STOP cannot be
      reinternalized after antibody binding. Thus, amino acids 335-337, which are
      important for the internalization of Gq-coupled TRHRs, are also required for the
      sequestration of functionally uncoupled TRHRs, and in addition, they act as an
      inhibitory signal that prevents constitutive receptor internalization.
      Specifically, the Cys residues at positions 335 and 337 are important for
      preventing constitutive TRHR internalization, because a mutant HA-C335S/C337S
      receptor was sequestered constitutively. We conclude that release from a negative
      regulatory internalization sequence or domain is important for HA-TRHR
      internalization and that the role of the CNC sequence in internalization is
      independent of functional TRHR-Gq coupling.

PMID- 8999942
TI  - Diverse genetic regulatory motifs required for murine adenosine deaminase gene
      expression in the placenta.
AB  - Murine adenosine deaminase (ADA) is a ubiquitous purine catabolic enzyme whose
      expression is subject to developmental and tissue-specific regulation. ADA is
      enriched in trophoblast cells of the chorioallantoic placenta and is essential
      for embryonic and fetal development. To begin to understand the genetic pathway
      controlling Ada gene expression in the placenta, we have identified and
      characterized a 770-base pair fragment located 5.4 kilobase pairs upstream of the
      Ada transcription initiation site, which directs reporter gene expression to the
      placenta of transgenic mice. The expression pattern of the reporter gene
      reflected that of the endogenous Ada gene in the placenta. Sequence analysis
      revealed potential binding sites for bHLH and GATA transcription factors. DNase I
      footprinting defined three protein binding regions, one of which was placenta
      specific. Mutations in the potential protein binding sites and footprinting
      regions resulted in loss of placental expression in transgenic mice. These
      findings indicate that multiple protein binding motifs are necessary for Ada
      expression in the placenta.

PMID- 8999943
TI  - Co-regulation and physical association of the 67-kDa monomeric laminin receptor
      and the alpha6beta4 integrin.
AB  - The interactions between tumor cells and laminin or other components of the
      extracellular matrix have been shown to play an important role in tumor invasion
      and metastasis. However, the role of the monomeric 67-kDa laminin receptor (67LR)
      remains unclear. We analyzed the regulation of 67LR expression under different
      culture conditions with respect to the expression of other well characterized
      laminin receptors. In A431 cells treated with laminin for different time periods,
      the regulation of 67LR expression correlated with expression of the alpha6
      integrin subunit but not with the expression of other laminin receptors.
      Moreover, cytokine treatment resulted in down-modulated expression of the alpha6
      integrin subunit and the 67LR. Co-regulation of the expression of the two
      receptors was further suggested by the observation that specific down-modulation
      of the alpha6-chain by antisense oligonucleotides was accompanied by a
      proportional decrease in the cell surface expression of 67LR. Biochemical
      analyses indicated co-immunoprecipitation of 67LR and the alpha6 subunit with an
      anti-alpha6 but not an anti-beta1 monoclonal antibody. Co-regulation of 67LR and
      alpha6 subunit expression, together with the physical association between the two
      receptors, supports the hypothesis that 67LR is an auxiliary molecule involved in
      regulating or stabilizing the interaction of laminin with the alpha6beta4
      integrin.

PMID- 8999944
TI  - Evidence that porcine pancreatic phospholipase A2 via its high affinity receptor
      stimulates extracellular matrix invasion by normal and cancer cells.
AB  - Cellular migration and extracellular matrix (ECM) invasion are some of the
      critical steps in embryonic implantation, inflammation, wound healing, and cancer
      metastasis. Extracellular phospholipases A2 (PLA2s), belonging to either group I
      (PLA2-I) or group II (PLA2-II), play an essential role in the generation of
      proinflammatory lipid mediators (e.g. prostaglandins, leukotrienes, etc.). Recent
      reports indicate that PLA2-I, in addition to its digestive function, has receptor
      mediated effects. For instance, PLA2-I, via its receptor, can induce cell
      proliferation and airway as well as vascular smooth muscle contraction. Here, we
      report that both porcine pancreatic and Naja naja PLA2s, in a dose-dependent
      manner, stimulate dramatic invasion of an artificial ECM (MatrigelTM) by NIH 3T3,
      mouse fibrosarcoma, and sarcoma cells in vitro, but it has no such effect on
      lymphoma and mastocytoma cells. That this is a receptor-mediated process is
      strongly suggested by the following findings. (a) While NIH 3T3, mouse
      fibrosarcoma, and sarcoma cells, which respond to PLA2-I stimulation, express
      high affinity PLA2-I receptor mRNA and protein, this receptor expression is not
      detectable in nonresponder lymphoma and mastocytoma cells. (b) There is a close
      correlation between the Kd values for 125I-PLA2-I binding to its receptor and the
      ED50 values for PLA2-I-induced ECM-invasion. (c) Catalytically inactivated PLA2-I
      is as effective as the active enzyme in stimulating invasion. (d) Suppression of
      PLA2-I receptor expression in responder cells causes inhibition of ECM invasion.
      (e) Treatment of the same cells with PLA2-I receptor-antibody also produces
      virtually identical effects. Taken together, our results identify a novel
      receptor-mediated function of PLA2-I and raises the possibility that
      extracellular PLA2s play important physiological as well as pathological roles
      via this receptor. To our knowledge, this is the first report of this novel
      receptor-mediated effect (i.e. ECM invasion) of PLA2-I on normal as well as
      malignant cancer cells.

PMID- 8999945
TI  - Recognition of phosphatidylserine on the surface of apoptotic spermatogenic cells
      and subsequent phagocytosis by Sertoli cells of the rat.
AB  - In a primary co-culture of spermatogenic and Sertoli cells of the rat, many
      spermatogenic cells die by apoptosis and are subsequently engulfed by Sertoli
      cells. We investigated the mechanism of this phagocytosis reaction. Testicular
      cells from 20-day-old rats were cultured, and spermatogenic cells and Sertoli
      cells were separated. When the recovered spermatogenic cells were maintained
      without Sertoli cells, the viability of the cells decreased and they became more
      susceptible to phagocytosis by Sertoli cells. Phagocytosis was severely impaired
      when liposomes containing acidic phospholipids, such as phosphatidylserine,
      phosphatidylinositol, and cardiolipin, were included in the reaction, whereas
      those consisting of neutral phospholipids showed little effect. Such anionic
      liposomes were more efficiently engulfed by Sertoli cells than were the other
      neutral liposomes. Also, the number of spermatogenic cells that exposed
      phosphatidylserine to the surface increased when cells were maintained in single
      culture. The results indicate that upon induction of spermatogenic cell
      apoptosis, phosphatidylserine and probably other acidic phospholipids, which are
      normally localized in the inner leaflet of the plasma membrane, translocate to
      the outer leaflet and serve as a signal for phagocytosis by Sertoli cells.

PMID- 8999946
TI  - Peroxidation of a specific tryptophan of metmyoglobin by hydrogen peroxide.
AB  - Globin-centered radicals at tyrosine and tryptophan residues and a peroxyl
      radical at an unknown location have been reported previously as products of the
      reaction of metmyoglobin with hydrogen peroxide. The peroxyl radical is shown
      here to be localized on tryptophan through the use of recombinant sperm whale
      myoglobin labeled with 13C at the indole ring C-3. Peroxyl radical formation was
      not prevented by site-directed mutations that replaced all three tyrosines, the
      distal histidine, or tryptophan 7 with non-oxidizable residues. In contrast,
      mutation of tryptophan 14 prevents peroxyl radical formation, implicating
      tryptophan 14 as the specific site of the peroxidation.

PMID- 8999947
TI  - Identification of potential tyrosine-containing endocytic motifs in the carboxyl
      tail and seventh transmembrane domain of the neurokinin 1 receptor.
AB  - Although agonist-induced endocytosis of G-protein-coupled receptors is critical
      for receptor desensitization and resensitization, receptor motifs that interact
      with the endocytic apparatus have not been adequately characterized. We examined
      the effects of mutating the rat neurokinin-1 receptor on endocytosis using 125I
      substance P, fluorescent substance P, and receptor antibodies. Substance P
      induced rapid internalization of wild-type receptors that were targeted to
      perinuclear endosomes. Truncation of the C-tail at residues 324, 342, and 354
      reduced internalization up to 60% and caused retention of receptors at the cell
      surface and in superficial endosomes. Mutation of Tyr-341 and Tyr-349 in
      potential tyrosine-containing endocytic motifs of the C-tail also impaired
      internalization. A Y305A mutant within the putative NPX2-3Y endocytic motif of
      the seventh transmembrane domain showed impaired signaling and was minimally
      expressed at the plasma membrane but was found in cytoplasmic vesicles. In
      contrast, a Y305F mutant signaled normally and was normally expressed at the
      plasma membrane but showed impaired internalization. Thus, endocytosis of the
      neurokinin 1 receptor relies on several tyrosine-containing sequences in the C
      tail and seventh transmembrane domain.

PMID- 8999948
TI  - The influence of the proliferating cell nuclear antigen-interacting domain of
      p21(CIP1) on DNA synthesis catalyzed by the human and Saccharomyces cerevisiae
      polymerase delta holoenzymes.
AB  - In eukaryotes, processive DNA synthesis catalyzed by DNA polymerases delta and
      epsilon (pol delta and epsilon) requires the proliferating cell nuclear antigen
      (PCNA). It has recently been shown that in humans (h), the PCNA function,
      required for both DNA replication and nucleotide excision repair, can be
      inactivated by p21(CIP1) due to a specific interaction between hPCNA and the
      carboxyl terminus of p21(CIP1). In this report, we show that Saccharomyces
      cerevisiae (S. cerevisiae) PCNA-dependent pol delta-catalyzed DNA synthesis was
      inhibited less efficiently than the human system by the intact p21(CIP1) protein
      and was unaffected by the p21(CIP1) carboxyl-terminal peptide (codons 139-160).
      This species-specific response of PCNA to p21(CIP1)-mediated inhibition of DNA
      synthesis results from a marked difference in the ability of h and S. cerevisiae
      PCNA to interact with p21(CIP1). As shown by binding studies using the surface
      plasmon resonance technique, hPCNA binds both full-length p21(CIP1) and the
      p21(CIP1) peptide-(139-160) stoichiometrically with a similar affinity (KD
      approximately 2.5 nM) while S. cerevisiae PCNA binds p21(CIP1) with approximately
      10-fold less affinity and does not interact with the p21(CIP1) peptide-(139-160).

PMID- 8999949
TI  - Sterically stabilized pH-sensitive liposomes. Intracellular delivery of aqueous
      contents and prolonged circulation in vivo.
AB  - Liposomes that destabilize at mildly acidic pH are efficient tools for delivering
      water-soluble drugs into the cell cytoplasm. However, their use in vivo is
      limited because of their rapid uptake from circulation by the reticuloendothelial
      system. Lipid-anchored polyethylene glycol (PEG-PE) prolongs the circulation time
      of liposomes by steric stabilization. We have found that addition of PEG-PE to
      the membrane of pH-sensitive liposomes composed of cholesteryl hemisuccinate
      (CHEMS) and dioleoylphosphatidylethanolamine (DOPE) confers steric stability to
      these vesicles. This modification significantly decreases the pH-dependent
      release of a charged water-soluble fluorophore, calcein, from liposomes suspended
      in buffer or cell culture medium. However, the ability of such liposomes to
      release calcein intracellularly, measured by a novel flow cytometry technique
      involving dual fluorescence labeling, remains unaltered. As expected, the release
      of calcein from liposomes endocytosed by cells is inhibited upon pretreatment of
      the cells with NH4Cl, an inhibitor of endosome acidification. The unique
      properties of these liposomes were also demonstrated in vivo. The distribution
      kinetics of 111In-containing CHEMS/DOPE/PEG-PE liposomes injected intravenously
      into rats has pharmacokinetic parameters similar to control, non-pH-sensitive,
      sterically stabilized CHEMS/distearoylphosphatidylcholine/PEG-PE liposomes. In
      contrast, regular pH-sensitive liposomes lacking the PEG-PE component are cleared
      rapidly. Sterically stabilized pH-sensitive liposomes may therefore be useful for
      the intracellular delivery in vivo of highly negatively charged molecules such as
      genes, antisense oligonucleotides, and ribozymes for the treatment of various
      diseases.

PMID- 8999950
TI  - Purification, visualization, and biophysical characterization of Kv1.3 tetramers.
AB  - The voltage-gated K+ channel of T-lymphocytes, Kv1.3, was heterologously
      expressed in African Green Monkey kidney cells (CV-1) using a vaccinia virus/T7
      hybrid expression system; each infected cell exhibited 10(4) to 5 x 10(5)
      functional channels on the cell surface. The protein, solubilized with detergent
      (3-[cholamidopropyl)dimethylammonio]-1-propanesulfonic acid or cholate), was
      purified to near-homogeneity by a single nickel-chelate chromatography step. The
      Kv1.3 protein expressed in vaccinia virus-infected cells and its purified
      counterpart are both modified by a approximately 2-kDa core-sugar moiety, most
      likely at a conserved N-glycosylation site in the external S1-S2 loop; absence of
      the sugar does not alter the biophysical properties of the channel nor does it
      affect expression levels. Purified Kv1.3 has an estimated size of approximately
      64 kDa in denaturing SDS-polyacrylamide electrophoresis gels, consistent with its
      predicted size based on the amino acid sequence. By sucrose gradient
      sedimentation, purified Kv1.3 is seen primarily as a single peak with an
      approximate mass of 270 kDa, compatible with its being a homotetrameric complex
      of the approximately 64-kDa subunits. When reconstituted in the presence of lipid
      and visualized by negative-staining electron microscopy, the purified Kv1.3
      protein forms small crystalline domains consisting of tetramers with dimensions
      of approximately 65 x 65 A. The center of each tetramer contains a stained
      depression which may represent the ion conduction pathway. Functional
      reconstitution of the Kv1.3 protein into lipid bilayers produces voltage
      dependent K+-selective currents that can be blocked by two high affinity peptide
      antagonists of Kv1.3, margatoxin and stichodactylatoxin.

PMID- 8999951
TI  - Oct-1 and CCAAT/enhancer-binding protein (C/EBP) bind to overlapping elements
      within the interleukin-8 promoter. The role of Oct-1 as a transcriptional
      repressor.
AB  - Interleukin-8 (IL-8), a potent neutrophil chemoattractant, can be expressed at
      high levels by many different cell types after immune stimulation. In contrast,
      expression of IL-8 in these same cells is virtually absent in the unstimulated
      state, demonstrating the tight regulation of the IL-8 gene. Although much is
      known about how this gene is transcriptionally activated after immune
      stimulation, little is known about the regulation of the IL-8 promoter in the
      absence of immune activation. In this study we examine how the IL-8 promoter is
      transcriptionally regulated in the uninduced state and how these mechanisms are
      altered in response to immune stimulation by IL-1beta. Electrophoretic mobility
      shift assay and transfection studies show that the IL-8 promoter is
      transcriptionally regulated by both positive and negative elements. Although the
      nuclear factor-kappaB (NFkappaB) element regulates only inducible activity of the
      IL-8 promoter in response to stimulation with IL-1beta, the AP-1 and
      CCAAT/Enhancer-binding Protein (C/EBP) elements influence both basal and
      inducible activities. In contrast to these three positive regulatory elements,
      the binding of the ubiquitously expressed POU-homeodomain transcription factor,
      Oct-1, strongly represses transcriptional activity of the IL-8 promoter by
      binding independently to an element overlapping that of C/EBP.

PMID- 8999952
TI  - Selective inhibition of cytosolic phospholipase A2 in activated human monocytes.
      Regulation of superoxide anion production and low density lipoprotein oxidation.
AB  - Our previous studies have shown that monocyte activation and release of O-2 are
      required for monocyte-mediated low density lipoprotein (LDL) lipid oxidation. We
      have also found that intracellular Ca2+ levels and protein kinase C activity are
      requisite participants in this potentially pathogenic process. In these studies,
      we further investigated the mechanisms involved in the oxidation of LDL lipids by
      activated human monocytes, particularly the potential contributions of the
      cytosolic phospholipase A2 (cPLA2) signaling pathway. The most well-studied
      cPLA2, has a molecular mass of 85 kDa and has been reported to be regulated by
      both Ca2+ and phosphorylation. We found that cPLA2 protein levels and cPLA2
      enzymatic activity were induced upon activation of human monocytes by opsonized
      zymosan. Pharmacologic inhibition of cPLA2 activity by AACOCF3, which has been
      reported to be a specific inhibitor of cPLA2 as compared with sPLA2, caused a
      dose-dependent inhibition of cPLA2 enzymatic activity and LDL lipid oxidation by
      activated human monocytes, whereas sPLA2 activity was not affected. To
      corroborate these findings, we used specific antisense oligonucleotides to
      inhibit cPLA2. We observed that treatment with antisense oligonucleotides caused
      suppression of both cPLA2 protein expression and enzymatic activity as well as
      monocyte-mediated LDL lipid oxidation. Furthermore, antisense oligonucleotide
      treatment caused a substantial inhibition of O-2 production by activated human
      monocytes. In parallel experimental groups, cPLA2 sense oligonucleotides did not
      affect cPLA2 protein expression, cPLA2 enzymatic activity, O-2 production, or
      monocyte-mediated LDL lipid oxidation. These studies support the proposal that
      cPLA2 activity is required for activated monocytes to oxidize LDL lipids.

PMID- 8999954
TI  - A subpopulation of estrogen receptors are modified by O-linked N
      acetylglucosamine.
AB  - Estrogen receptors (ER) are ligand-inducible transcription factors regulated by
      Ser(Thr)-O-phosphorylation. Many transcription factors and eukaryotic RNA
      polymerase II itself are also dynamically modified by Ser(Thr)-O-linked N
      acetylglucosamine moieties (O-GlcNAc). Here we report that subpopulations of
      murine, bovine, and human estrogen receptors are modified by O-GlcNAc. O-GlcNAc
      moieties were detected on insect cell-expressed, mouse ER (mER) by probing with
      bovine milk galactosyltransferase, followed by structural analysis. Wheat germ
      agglutinin-Sepharose affinity chromatography also readily detected terminal
      GlcNAc residues on subpopulations of ER purified from calf uterus, from human
      breast cancer cells (MCF-7), or from mER produced by in vitro translation. These
      data suggest that greater than 10% of these populations of estrogen receptors
      bear O-GlcNAc. Site mapping of insect cell expressed mER localized one major site
      of O-GlcNAc addition to Thr-575, within a PEST region of the carboxyl-terminal F
      domain. Based upon their relative resistance to both hexosaminidase and to in
      vitro galactosylation, O-GlcNAc moieties appear to be largely buried on native
      mER. This dynamic saccharide modification, like phosphorylation, may play a role
      in modulating the dimerization, stability, or transactivation functions of
      estrogen receptors.

PMID- 8999953
TI  - Transactivation of the human renin promoter by the cyclic AMP/protein kinase A
      pathway is mediated by both cAMP-responsive element binding protein-1 (CREB)
      dependent and CREB-independent mechanisms in Calu-6 cells.
AB  - We examined the DNA sequence and transcription factor requirements for cAMP
      induced transactivation of the human renin promoter using Calu-6 cells that
      express human renin mRNA endogenously. A series of constructs containing 896 base
      pairs of human renin 5'-flanking DNA fused to the luciferase gene and containing
      either the native, a consensus, or a nonfunctional cAMP response element (CRE)
      were used to assess DNA sequence requirements mediating the cAMP response.
      Expression vectors encoding the CREB-1 transcription factor, a dominant negative
      mutant form of CREB-1, and the catalytic subunit of protein kinase A (PKA) were
      used to assess transcription factor requirements mediating the cAMP response.
      Forskolin treatment alone only caused a 2-3-fold activation of the HREN promoter
      in Calu-6 cells, but nearly a 10-fold activation in JEG-3 cells, which do not
      express renin but are highly responsive to cAMP. Gel shift assays revealed the
      binding of five specific DNA-protein complexes consisting of the ATF-1 and CREB-1
      transcription factors, one of which was an ATF-1.CREB-1 heterodimer suggesting
      the potential for regulation of CREB-1 activity by ATF-1. However, over
      expression of CREB-1 did not significantly enhance forskolin-induced human renin
      transcriptional activity. Transfection of both Calu-6 and JEG-3 cells with a PKA
      expression vector resulted in a 10-fold induction of human renin transcriptional
      activity in constructs containing the native or consensus CRE and 5-fold
      activation in a construct containing a nonfunctional CRE. We confirmed that the
      PKA response has both a CREB-dependent and CREB-independent component by
      demonstrating that the PKA response was abolished by co-transfection of a
      dominant negative mutant form of CREB-1 into cells containing the native or
      consensus CRE construct but not in cells containing the nonfunctional CRE
      construct. We therefore conclude that the human renin promoter can be
      transcriptionally activated in a renin expressing cell line through the cAMP-PKA
      pathway and is mediated by both a CREB-dependent and CREB-independent mechanism.

PMID- 8999955
TI  - Dissection of glutathionylspermidine synthetase/amidase from Escherichia coli
      into autonomously folding and functional synthetase and amidase domains.
AB  - The bifunctional glutathionylspermidine synthetase/amidase from Escherichia coli
      catalyzes both the ATP-dependent formation of an amide bond between N1 of
      spermidine (N-(3-amino)propyl-1, 4-diaminobutane) and the glycine carboxylate of
      glutathione (gamma-Glu-Cys-Gly) and the opposing hydrolysis of this amide bond
      (Bollinger, J. M., Jr., Kwon, D. S., Huisman, G. W., Kolter, R., and Walsh, C. T.
      (1995) J. Biol. Chem. 270, 14031-14041). In our previous work describing its
      initial characterization, we proposed that the 619-amino acid (70 kDa) protein
      might possess separate amidase (N-terminal) and synthetase (C-terminal) domains.
      In the present study, we have confirmed this hypothesis by expression of
      independently folding and functional amidase and synthetase modules. A fragment
      containing the C-terminal 431 amino acids (50 kDa) has synthetase activity only,
      with steady-state kinetic parameters similar to the full-length protein. A
      fragment containing the N-terminal 225 amino acids (25 kDa) has amidase activity
      only and is significantly activated relative to the full-length protein for
      hydrolysis of glutathionylspermidine analogs. This observation suggests that the
      amidase activity in the full-length protein is negatively autoregulated. The
      amidase active site catalyzes hydrolysis of amide and ester derivatives of
      glutathione (e.g. glutathione ethyl ester and glutathione amide) but lacks
      activity toward acetylspermidine (N1 and N8) and acetylspermine (N1), indicating
      that glutathione provides the primary recognition determinants for
      glutathionylspermidine amide bond cleavage. No metal ion is required for the
      amidase activity. A tetrahedral phosphonate analogue of glutathionylspermidine,
      designed as a mimic of the proposed tetrahedral intermediate for either reaction,
      inhibits the synthetase activity (Ki approximately 10 microM) but does not
      inhibit the amidase activity.

PMID- 8999956
TI  - Identification, sequence, and expression of an invertebrate caveolin gene family
      from the nematode Caenorhabditis elegans. Implications for the molecular
      evolution of mammalian caveolin genes.
AB  - Caveolae are vesicular organelles that represent an appendage of the plasma
      membrane. Caveolin, a 21-24-kDa integral membrane protein, is a principal
      component of caveolae membranes in vivo. Caveolin has been proposed to function
      as a plasma membrane scaffolding protein to organize and concentrate signaling
      molecules within caveolae, including heterotrimeric G proteins (alpha and
      betagamma subunits). In this regard, caveolin interacts directly with Galpha
      subunits and can functionally regulate their activity. To date, three cDNAs
      encoding four subtypes of caveolin have been described in vertebrates. However,
      evidence for the existence of caveolin proteins in less complex organisms has
      been lacking. Here, we report the identification, cDNA sequence and genomic
      organization of the first invertebrate caveolin gene, Cavce (for caveolin from
      Caenorhabditis elegans). The Cavce gene, located on chromosome IV, consists of
      two exons interrupted by a 125-nucleotide intron sequence. The region of Cavce
      that is strictly homologous to mammalian caveolins is encoded by a single exon in
      Cavce. This suggests that mammalian caveolins may have evolved from the second
      exon of Cavce. Cavce is roughly equally related to all three known mammalian
      caveolins and, thus, could represent a common ancestor. Remarkably, the
      invertebrate Cavce protein behaves like mammalian caveolins: (i) Cavce forms a
      high molecular mass oligomer, (ii) assumes a cytoplasmic membrane orientation,
      and (iii) interacts with G proteins. A 20-residue peptide encoding the predicted
      G protein binding region of Cavce possesses "GDP dissociation inhibitor-like
      activity" with the same potency as described earlier for mammalian caveolin-1.
      Thus, caveolin appears to be structurally and functionally conserved from worms
      to man. In addition, we find that there are at least two caveolin-related genes
      expressed in C. elegans, defining an invertebrate caveolin gene family. These
      results establish the nematode C. elegans as an invertebrate model system to
      study caveolae and caveolin in vivo.

PMID- 8999958
TI  - Ceramide-induced translocation of protein kinase C-delta and -epsilon to the
      cytosol. Implications in apoptosis.
AB  - Ceramide is now recognized as an intracellular lipid signal mediator, which
      induces various kinds of cell functions including apoptosis. Ceramide-induced
      apoptosis was reported to be blocked by 12-O-tetradecanoylphorbol 13-acetate, a
      protein kinase C (PKC) activator, but its mechanism remained unclear. Therefore,
      we investigated whether ceramide has any effects on PKC in the induction of
      apoptosis. We here report that N-acetylsphingosine (synthetic membrane-permeable
      ceramide) induced translocation of PKC-delta and -epsilon isozymes from the
      membrane to the cytosol within 5 min in human leukemia cell lines. Treatment with
      sphingomyelinase, tumor necrosis factor-alpha, or anti-Fas antibody, all of which
      can induce apoptosis by generating natural ceramide, similarly induced cytosolic
      translocation of PKC-delta and -epsilon. In Fas-resistant cells anti-Fas antibody
      did not induce cytosolic translocation of PKC-delta and -epsilon because of no
      generation of ceramide, whereas N-acetylsphingosine induced apoptosis with
      cytosolic translocation of PKC-delta and -epsilon. Furthermore, both 12-O
      tetradecanoylphorbol 13-acetate and a nonspecific kinase inhibitor,
      staurosporine, prevented ceramide-induced apoptosis by inhibiting cytosolic
      translocation of PKC-delta and -epsilon. These data suggest that cytosolic
      translocation of PKC-delta and -epsilon plays an important role in ceramide
      mediated apoptosis.

PMID- 8999957
TI  - Membrane type 1 matrix metalloproteinase digests interstitial collagens and other
      extracellular matrix macromolecules.
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed on cancer cell
      membranes and activates the zymogen of MMP-2 (gelatinase A). We have recently
      isolated MT1-MMP complexed with tissue inhibitor of metalloproteinases 2 (TIMP-2)
      and demonstrated that MT1-MMP exhibits gelatinolytic activity by gelatin
      zymography (Imai, K., Ohuchi, E., Aoki, T., Nomura, H., Fujii, Y., Sato, H.,
      Seiki, M., and Okada, Y. (1996) Cancer Res. 56, 2707-2710). In the present study,
      we have further purified to homogeneity a deletion mutant of MT1-MMP lacking the
      transmembrane domain (DeltaMT1) and native MT1-MMP secreted from a human breast
      carcinoma cell line (MDA-MB-231 cells) and examined their substrate
      specificities. Both proteinases are active, without any treatment for activation,
      and digest type I (guinea pig), II (bovine), and III (human) collagens into
      characteristic 3/4 and 1/4 fragments. The cleavage sites of type I collagen are
      the Gly775-Ile776 bond for alpha1(I) chains and the Gly775-Leu776 and Gly781
      Ile782 bonds for alpha2(I) chains. DeltaMT1 hydrolyzes type I collagen 6.5- or 4
      fold more preferentially than type II or III collagen, whereas MMP-1 (tissue
      collagenase) digests type III collagen more efficiently than the other two
      collagens. Quantitative analyses of the activity of DeltaMT1 and MMP-1 indicate
      that DeltaMT1 is 5-7.1-fold less efficient at cleaving type I collagen. On the
      other hand, gelatinolytic activity of DeltaMT1 is 8-fold higher than that of MMP
      1. DeltaMT1 also digests cartilage proteoglycan, fibronectin, vitronectin and
      laminin-1 as well as alpha1-proteinase inhibitor and alpha2-macroglobulin. The
      activity of DeltaMT1 on type I collagen is synergistically increased with co
      incubation with MMP-2. These results indicate that MT1-MMP is an extracellular
      matrix-degrading enzyme sharing the substrate specificity with interstitial
      collagenases, and suggest that MT1-MMP plays a dual role in pathophysiological
      digestion of extracellular matrix through direct cleavage of the substrates and
      activation of proMMP-2.

PMID- 8999960
TI  - GATA-1 DNA binding activity is down-regulated in late S phase in erythroid cells.
AB  - We have set out to test a model for tissue-specific gene expression that relies
      on the early replication of expressed genes to sequester limiting activating
      transcription factors. Using an erythroid cell line, we have tested the changes
      in the DNA binding activity of the lineage-restricted transcription factor GATA-1
      through the cell cycle. We find that GATA-1 activity is low in G1, peaks in mid-S
      phase, and then decreases in G2/M. In contrast, the binding activities of two
      ubiquitous transcription factors, Oct1 and Sp1, remain high in G2/M. GATA-1
      protein and mRNA vary in a similar manner through the cell cycle, suggesting that
      the expression of the gene or the stability of its message is regulated. Although
      a number of transcription factors involved in the control of the cell cycle or
      DNA replication have been shown to peak in S phase, this is the first example of
      a lineage-restricted transcription factor displaying S phase-specific DNA binding
      activity. One interpretation of these data leads to a model in which the peak in
      GATA-1 DNA binding amplifies the effect of early replication on the activation of
      erythroid-specific genes at the same time as preventing activation of non
      erythroid genes containing GATA-responsive elements. These results may also
      relate to recent data implicating GATA-1 function in apoptosis and cell cycle
      progression.

PMID- 8999959
TI  - Physical and functional interactions between the transcriptional inhibitors Id3
      and ITF-2b. Evidence toward a novel mechanism regulating muscle-specific gene
      expression.
AB  - We have used an interaction cloning strategy to identify an inhibitory isoform of
      the ITF-2 transcription factor, ITF-2b, that interacts with the transcriptional
      inhibitor Id3/HLH462. The interaction was confirmed in vitro, and inside intact
      myogenic C2C12 cells. As expected, overexpression of either Id3/HLH462 or ITF-2b
      effectively inhibited the activation of the muscle-specific creatine kinase
      promoter by the myogenic transcription factor MyoD. However, when overexpressed
      simultaneously, ITF-2b and Id3/HLH462 counteracted each other's inhibitory effect
      to produce a reduced overall inhibition. Moreover, while ITF-2b inhibited the
      creatine kinase promoter, it acted as a weak transactivator on an artificial
      promoter consisting of three tandem copies of the consensus myogenic factor DNA
      binding site. Further investigation indicated that the ITF-2b/MyoD heterodimer
      bound to its specific DNA binding site in vitro, and the DNA binding was
      effectively blocked by Id3/HLH462. Additional analysis revealed the presence of
      transcripts for both the activating (ITF-2a) and inhibitory (ITF-2b) isoforms in
      differentiating C2C12 cultures, suggesting that both isoforms might participate
      in regulating the differentiation process. Taken together, this study reveals a
      more complex pattern of regulatory interactions involving the helix-loop-helix
      proteins than was previously anticipated.

PMID- 8999961
TI  - Evidence for different mechanisms of growth inhibition of T-cell lymphoma by
      phorbol esters and concanavalin A.
AB  - Stimuli that are mitogenic for mature T-cells induce cell cycle arrest in some T
      cell tumors and T-cell hybridomas. The molecular mechanism of this growth
      inhibition is poorly understood. In this report, we show that in EL4, a murine T
      lymphoma cell line, stimulation with concanavalin A or treatment with phorbol 13
      myristate 12-acetate (PMA) inhibit growth, due to cell cycle arrest at both the
      G1 and the G2/M phases. The block at the G1 phase is accompanied by the
      appearance of a hypophosphorylated form of the retinoblastoma protein (pRb), due
      to the inhibition of G1 cyclin-Cdk complexes. However, the molecular mechanisms
      leading to this G1 cell cycle arrest differ between concanavalin A and PMA:
      concanavalin A inhibits both cyclin E-Cdk2 and cyclin D-Cdk4 complexes, while PMA
      inhibits only cyclin E-Cdk2. We demonstrate that concanavalin A inhibits cyclin D
      Cdk4 activity by decreasing the amount of cyclin D. The inhibition of cyclin E
      Cdk2 by both concanavalin A and PMA is due to increased binding of the Cdk
      inhibitor p21 to this complex. However, while stimulation of the cells with
      concanavalin A did not result in an evident increase of the total level of p21,
      treatment of the cells with PMA increased p21 levels significantly. Our results
      indicate, furthermore, that the G2/M block results from the inhibition of cyclin
      A- and cyclin B1-associated kinase activities. As for cyclin E-Cdk2, the
      inhibition of the cyclin A-Cdk2 complex is due to increased binding of the p21
      inhibitor.

PMID- 8999962
TI  - Characterization of p150, an adaptor protein for the human phosphatidylinositol
      (PtdIns) 3-kinase. Substrate presentation by phosphatidylinositol transfer
      protein to the p150.Ptdins 3-kinase complex.
AB  - Genetic and biochemical studies have shown that the phosphatidylinositol (PtdIns)
      3-kinase encoded by the yeast VPS34 gene is required for the efficient sorting
      and delivery of proteins to the vacuole. A human homologue of the yeast VPS34
      gene product has recently been characterized as part of a complex with a cellular
      protein of 150 kDa (Volinia, S., Dhand, R., Vanhaesebroeck, B., MacDougall, L.
      K., Stein, R., Zvelebil, M. J., Domin, J., Panaretou, C., and Waterfield, M. D.
      (1995) EMBO J. 14, 3339-3348). Here, cDNA cloning is used to show that the amino
      acid sequence of this protein, termed p150, is 29.6% identical and 53% similar to
      the yeast Vps15p protein, an established regulator of Vps34p. Northern blot
      analysis showed a ubiquitous tissue distribution for p150 similar to that
      previously observed with PtdIns 3-kinase. Recombinant p150 associated with PtdIns
      3-kinase in vitro in a stable manner, resulting in a 2-fold increase in lipid
      kinase activity. Addition of phosphatidylinositol transfer protein (PI-TP)
      further stimulated the lipid kinase activity of the p150.PtdIns 3-kinase complex
      3-fold. A PtdIns 3-kinase activity could also be co-immunoprecipitated from human
      cell lysates using anti-PI-TP antisera. This observation demonstrates that an
      interaction between a PtdIns 3-kinase and PI-TP occurs in vivo, which further
      implicates lipid transfer proteins in the regulation of PtdIns 3-kinase activity.
      These results suggest that the Vps15p.Vps34p complex has been conserved from
      yeast to man and in both species is involved in protein trafficking.

PMID- 8999963
TI  - Phosphorylation of the V2 vasopressin receptor.
AB  - The V2 vasopressin receptor undergoes ligand-induced sequestration and
      desensitization (Birnbaumer, M., Antaramian, A., Themmen, A. P. N., and Gilbert,
      S. (1992) J. Biol. Chem. 267, 11783-11788). The V2 receptor expressed in
      transfected cells labeled with [32P] orthophosphate was phosphorylated following
      the addition of 100 nM arginine vasopressin (AVP). Phosphorylation was complete 5
      min after addition of AVP, and was not stimulated by increased levels of Ca2+ or
      cAMP. The half-maximal dose of AVP that stimulated phosphorylation was 2.4 +/-
      0.4 nM, similar to the receptor KD of 4. 5 +/- 0.4 nM. The role of
      phosphorylation on receptor desensitization was investigated by studying two
      vasopressin receptors 14 and 27 amino acids shorter than the wild type receptor.
      The missing segments were not needed for normal ligand binding or coupling to Gs,
      but the last 14 amino acids were required for phosphorylation. The truncated
      receptors exposed to 100 nM AVP were sequestered and desensitized. The R137H V2R
      mutant receptor that binds vasopressin with wild type-like affinity and does not
      couple to Gs (Rosenthal, W., Antaramian, A., Gilbert, S., and Birnbaumer, M.
      (1993) J. Biol. Chem. 268, 13030-13033) was phosphorylated and subjected to
      ligand-induced sequestration. These results established that phosphorylation is
      not essential for sequestration and desensitization of the V2 vasopressin
      receptor. Furthermore, they revealed that the conformation acquired after ligand
      occupancy is necessary for receptor phosphorylation and sequestration, while
      coupling to Gs is not.

PMID- 8999964
TI  - Distinct regions specify the targeting of otefin to the nucleoplasmic side of the
      nuclear envelope.
AB  - Otefin is a 45-kDa nuclear envelope protein with no apparent homology to other
      known proteins. It includes a large hydrophilic domain, a single carboxyl
      terminal hydrophobic sequence of 17 amino acids, and a high content of serine and
      threonine residues. Cytological labeling located otefin on the nucleoplasmic side
      of the nuclear envelope. Chemical extraction of nuclei from Drosophila embryos
      revealed that otefin is a peripheral protein whose association with the nuclear
      envelope is stronger than that of lamin. Deletion mutants of otefin were
      expressed in order to identify regions that direct otefin to the nuclear
      envelope. These experiments revealed that the hydrophobic sequence at the
      carboxyl terminus is essential for correct targeting to the nuclear envelope,
      whereas additional regions in the hydrophilic domain of otefin are required for
      its efficient targeting and stabilization in the nuclear envelope.

PMID- 8999965
TI  - Cell type-specific protein-DNA interactions at the cAMP response elements of the
      prohormone convertase 1 promoter. Evidence for additional transactivators
      distinct from CREB/ATF family members.
AB  - The proximal promoter region of the neuroendocrine-specific human prohormone
      convertase 1 (PC1) gene contains two distinct cAMP response elements (CRE-1 and
      CRE-2). Both elements are essential in directing the cAMP-mediated hormonal
      regulation of PC1 gene transcription. In this study, we have demonstrated that
      CRE-1 binds several trans-acting factors. In electrophoretic mobility shift assay
      experiments with nuclear extracts prepared from neuroendocrine AtT-20 and beta
      TC3 cells and non-neuroendocrine COS-1 cells, three specific protein-DNA
      complexes (I-III) were detected. Complexes II and III were shown to contain CREB
      1 and ATF-1, respectively. The most slowly migrating complex I was only detected
      with the neuroendocrine cell lines and appeared to comprise a c-Jun-containing
      heterodimer. In addition, CRE-2 was shown to bind a protein that was only
      detected in nuclear extracts derived from the neuroendocrine cell lines. Antibody
      supershift experiments indicated that both the c-Jun-interacting protein in CRE-1
      complex I and the CRE-2-interacting protein are distinct from known members of
      the basic domain, leucine zipper family of transcription factors. UV cross
      linking experiments demonstrated that these potential novel proteins are
      approximately 100 and 60 kDa in size, respectively. Site-specific mutagenesis
      experiments demonstrated that the formation of both CRE-1 and CRE-2 complexes is
      correlated with the transcriptional activity of the proximal PC1 promoter as has
      been shown in transient transfections with wild-type and mutant promoter
      constructs. In addition, it was shown that both CREB-1 and ATF-1 transactivate
      the human PC1 promoter in transient transfection experiments.

PMID- 8999966
TI  - Rapamycin dissociates p70(S6K) activation from DNA synthesis stimulated by
      bombesin and insulin in Swiss 3T3 cells.
AB  - Phosphorylation and subsequent activation of p70 S6 kinase (S6K) are events that
      are highly conserved in the cellular response to mitogens. The neuropeptide
      bombesin, which is a potent mitogen for Swiss 3T3 cells, stimulated a time- and
      dose-dependent activation of p70(S6K) as determined by gel mobility shift and
      immune complex kinase assays. This effect was inhibited by the immunosuppressant
      rapamycin at 10 nM, which also completely abolished bombesin-stimulated DNA
      synthesis at identical concentrations. In striking contrast, the combination of
      bombesin and insulin in synergy stimulated maximum DNA synthesis in these cells
      despite persistent inhibition of p70(S6K) by rapamycin throughout G1. These
      results indicate that activation of p70(S6K) is not required for the transition
      of quiescent cells to the S phase of the cell cycle. The inhibitory effects of
      rapamycin on bombesin-stimulated cell cycle progression did not involve
      accumulation of the cyclin-dependent kinase inhibitor p27(kip1) but a striking
      inhibition of the expression of cyclin D1. This effect was circumvented by
      bombesin with insulin, suggesting that a rapamycin-insensitive pathway stimulated
      by this combination leads to cyclin D1 expression. Thus, these findings,
      dissociating the mitogenic effects of bombesin in synergy with insulin from
      activation of p70(S6K), support the hypothesis that this kinase is a component of
      one of the parallel pathways that can lead to DNA synthesis rather than an
      obligatory point of convergence in mitogenic signaling.

PMID- 8999967
TI  - Translational regulation of lipoprotein lipase by epinephrine involves a trans
      acting binding protein interacting with the 3' untranslated region.
AB  - To better characterize the translational regulation of lipoprotein lipase (LPL)
      by epinephrine, cytoplasmic extracts were prepared from 3T3-L1 adipocytes, 3T3
      F442A adipocytes, and other nonadipocyte cell lines (C2 cells, 3T3 fibroblasts,
      and Chinese hamster ovary cells). After treatment with epinephrine, cell extracts
      from the adipocytes inhibited LPL translation in an in vitro translation assay,
      whereas extracts from the C2 cells and 3T3 fibroblasts did not affect LPL
      translation. To identify the region on the LPL mRNA that controlled translation,
      in vitro translation was carried out using constructs containing different LPL
      sequences. Specific deletion of the first 50 (1601-1650) nucleotides of the 3'
      untranslated region (UTR) resulted in a loss of translation inhibition. The
      addition of LPL 3' UTR to a heterologous reporter gene construct resulted in an
      inhibition of translation. Inhibition of the reporter LPL 3' UTR translation was
      demonstrated by the addition of epinephrine-treated cell extracts to an in vitro
      translation assay, as well as by transfection of this construct into 3T3-F442A
      cells, followed by treatment of the cells with epinephrine. Competition for a
      trans-acting binding protein was demonstrated by the addition of sense mRNA
      strands corresponding to the proximal 135 nucleotides of the 3' UTR of LPL. To
      identify a RNA-binding protein, adipocyte extracts were incubated with 32P
      labeled RNA sequences followed by RNase treatment. The epinephrine-treated cell
      extract protected a fragment of RNA when the RNA included sequences on the
      proximal 3' UTR of LPL. Cross-linking of this protected fragment and analysis by
      SDS-polyacrylamide gel electrophoresis revealed a protein that migrated at about
      30 kDa. Thus, the addition of epinephrine to 3T3 adipocytes results in an
      inhibition of translation through the production of a RNA-binding protein that
      binds to a region on the proximal 3' UTR of the LPL mRNA.

PMID- 8999968
TI  - Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of
      syntaxin.
AB  - unc-13 mutants in Caenorhabditis elegans are characterized by a severe deficit in
      neurotransmitter release. Their phenotype is similar to that of the C. elegans
      unc-18 mutation, which is thought to affect synaptic vesicle docking to the
      active zone. This suggests a crucial role for the unc-13 gene product in the
      mediation or regulation of synaptic vesicle exocytosis. Munc13-1 is one of three
      closely related rat homologues of unc-13. Based on the high degree of similarity
      between unc-13 and Munc13 proteins, it is thought that their essential function
      has been conserved from C. elegans to mammals. Munc13-1 is a brain-specific
      peripheral membrane protein with multiple regulatory domains that may mediate
      diacylglycerol, phospholipid, and calcium binding. In the present study, we
      demonstrate by three independent methods that the C terminus of Munc13-1
      interacts directly with a putative coiled coil domain in the N-terminal part of
      syntaxin. Syntaxin is a component of the exocytotic synaptic core complex, a
      heterotrimeric protein complex with an essential role in transmitter release.
      Through this interaction, Munc13-1 binds to a subpopulation of the exocytotic
      core complex containing synaptobrevin, SNAP25 (synaptosomal-associated protein of
      25 kDa), and syntaxin, but to no other tested syntaxin-interacting or core
      complex-interacting protein. The site of interaction in syntaxin is similar to
      the binding site for the unc-18 homologue Munc18, but different from that of all
      other known syntaxin interactors. These data indicate that unc-13-related
      proteins may indeed be involved in the mediation or regulation of synaptic
      vesicle exocytosis by modulating or regulating core complex formation. The
      similarity between the unc-13 and unc-18 phenotypes is paralleled by the
      coincidence of the binding sites for Munc13-1 and Munc18 in syntaxin. It is
      possible that the phenotype of unc-13 and unc-18 mutations is caused by the
      inability of the respective mutated gene products to bind to syntaxin.

PMID- 8999969
TI  - Identification of an actin binding region and a protein kinase C phosphorylation
      site on human fascin.
AB  - Fascin is a 55-58-kDa actin-bundling protein, the actin binding of which is
      regulated by phosphorylation (Yamakita, Y., Ono, S., Matsumura, F., and
      Yamashiro, S. (1996) J. Biol. Chem. 271, 12632-12638). To understand the
      mechanism of fascin-actin interactions, we dissected the actin binding region and
      its regulatory site by phosphorylation of human fascin. First, we found that the
      C-terminal half constitutes an actin binding domain. Partial digestion of human
      recombinant fascin with trypsin yielded the C-terminal fragment with molecular
      masses of 32, 30, and 27 kDa. The 32- and 27-kDa fragments purified as a mixture
      formed a dimer and bound to F-actin at a saturation ratio of 1 dimer:11 actin
      molecules with an affinity of 1.4 x 10(6) M-1. Second, we identified the
      phosphorylation site of fascin as Ser-39 by sequencing a tryptic phosphopeptide
      purified by chelating column chromatography followed by C-18 reverse phase high
      performance liquid chromatography. Peptide map analyses revealed that the
      purified peptide represented the major phosphorylation site of in vivo as well as
      in vitro phosphorylated fascin. The mutation replacing Ser-39 with Ala eliminated
      the phosphorylation-dependent regulation of actin binding of fascin, indicating
      that phosphorylation at this site regulates the actin binding ability of fascin.

PMID- 8999971
TI  - Identification of a human cDNA clone for lysosomal type Ca2+-independent
      phospholipase A2 and properties of the expressed protein.
AB  - A Ca2+-independent phospholipase A2 (PLA2) maximally active at pH 4 and
      specifically inhibited by the transition-state analogue 1-hexadecyl-3
      trifluoroethylglycero-sn-2-phosphomethanol (MJ33) was isolated from rat lungs.
      The sequence for three internal peptides (35 amino acids) was used to identify a
      1653-base pair cDNA clone (HA0683) from a human myeloblast cell line. The deduced
      protein sequence of 224 amino acids contained a putative motif (GXSXG) for the
      catalytic site of a serine hydrolase, but showed no significant homology to known
      phospholipases. Translation of mRNA produced from this clone in both a wheat germ
      system and Xenopus oocytes showed expression of PLA2 activity with properties
      similar to the rat lung enzyme. Apparent kinetic constants for PLA2 with
      dipalmitoylphosphatidylcholine as substrate were Km = 0.25 mM and Vmax = 1.89
      nmol/h. Activity with alkyl ether phosphatidylcholine as substrate was decreased
      significantly compared with diacylphosphatidylcholine. Significant
      lysophospholipase, phospholipase A1, or 1-O-alkyl-2-acetyl-sn-glycero-3
      phosphocholine acetylhydrolase activity was not observed. Enzyme activity was
      insensitive to p-bromophenacyl bromide, bromoenol lactone,
      trifluoromethylarachidonoyl ketone, mercaptoethanol, and ATP, but was inhibited
      by MJ33 and diethyl p-nitrophenyl phosphate, a serine protease inhibitor. SDS
      polyacrylamide gel electrophoresis with autoradiography of the translated
      [35S]methionine-labeled protein confirmed a molecular mass of 25.8 kDa, in good
      agreement with the enzyme isolated from rat lung. By Northern blot analysis, mRNA
      corresponding to this clone was present in both rat lung and isolated rat
      granular pneumocytes. These results represent the first molecular cloning of a
      cDNA for the lysosomal type Ca2+-independent phospholipase A2 group of enzymes.

PMID- 8999970
TI  - Activities of the microtubule-stabilizing agents epothilones A and B with
      purified tubulin and in cells resistant to paclitaxel (Taxol(R)).
AB  - Epothilones A and B, natural products with minimal structural analogy to taxoids,
      have effects similar to those of paclitaxel (Taxol(R)) in cultured cells and on
      microtubule protein, but differ from paclitaxel in retaining activity in
      multidrug-resistant cells. We examined interactions of the epothilones with
      purified tubulin and additional cell lines, including a paclitaxel-resistant
      ovarian carcinoma line with an altered beta-tubulin. The epothilones, like
      paclitaxel, induced tubulin to form microtubules at low temperatures and without
      GTP and/or microtubule-associated proteins. The epothilones are competitive
      inhibitors of the binding of [3H]paclitaxel to tubulin polymers. The apparent Ki
      values for epothilones A and B were 1.4 and 0.7 microM by Hanes analysis and 0.6
      and 0.4 microM by Dixon analysis. In the paclitaxel-sensitive human cell lines we
      examined, epothilone B had greater antiproliferative activity than epothilone A
      or paclitaxel, while epothilone A was usually less active than paclitaxel. A
      multidrug-resistant colon carcinoma line and the paclitaxel-resistant ovarian
      line retained sensitivity to the epothilones. With Potorous tridactylis kidney
      epithelial (PtK2) cells examined by indirect immunofluorescence, microtubule
      bundles appeared more rapidly following epothilone B treatment, and there were
      different proportions of various mitotic aberrations following treatment with
      different drugs.

PMID- 8999973
TI  - Abasic translesion synthesis by DNA polymerase beta violates the "A-rule". Novel
      types of nucleotide incorporation by human DNA polymerase beta at an abasic
      lesion in different sequence contexts.
AB  - The "A-rule" reflects the preferred incorporation of dAMP opposite abasic lesions
      in Escherichia coli in vivo. DNA polymerases (pol) from procaryotic and
      eucaryotic organisms incorporate nucleotides opposite abasic lesions in
      accordance with the A-rule. However, recent in vivo data demonstrate that A is
      not preferentially incorporated opposite abasic lesions in eucaryotes. Purified
      human DNA polymerases beta and alpha are used to measure the specificity of
      nucleotide incorporation at a site-directed tetrahydrofuran abasic lesion, in 8
      sequence contexts, varying upstream and downstream bases adjacent to the lesion.
      Extension past the lesion is measured in 4 sequence contexts, varying the
      downstream template base. Pol alpha strongly favors incorporation of dAMP
      directly opposite the lesion. In marked contrast, pol beta violates the A-rule
      for incorporation directly opposite the lesion. In addition to incorporation
      taking place directly opposite the lesion, we also analyze misalignment
      incorporation directed by a template base downstream from the lesion. Lesion
      bypass by pol beta occurs predominantly by "skipping over" the lesion, by
      insertion of a nucleotide complementary to an adjacent downstream template site.
      Misalignment incorporation for pol beta occurs by a novel "dNTP-stabilized"
      mechanism resulting in both deletion and base substitution errors. In contrast,
      pol alpha shows no propensity for this type of synthesis. The misaligned DNA
      structures generated during dNTP-stabilized lesion bypass do not conform to
      misaligned structures reported previously.

PMID- 8999972
TI  - Activation of protein kinase C (alpha, beta, and zeta) by insulin in 3T3/L1
      cells. Transfection studies suggest a role for PKC-zeta in glucose transport.
AB  - We presently studied (a) insulin effects on protein kinase C (PKC) and (b)
      effects of transfection-induced, stable expression of PKC isoforms on glucose
      transport in 3T3/L1 cells. In both fibroblasts and adipocytes, insulin provoked
      increases in membrane PKC enzyme activity and membrane levels of PKC-alpha and
      PKC-beta. However, insulin-induced increases in PKC enzyme activity were apparent
      in both non-down-regulated adipocytes and adipocytes that were down-regulated by
      overnight treatment with 5 microM phorbol ester, which largely depletes PKC
      alpha, PKC-beta, and PKC-epsilon, but not PKC-zeta. Moreover, insulin provoked
      increases in the enzyme activity of immunoprecipitable PKC-zeta. In transfection
      studies, stable overexpression of wild-type or constitutively active forms of PKC
      alpha, PKC-beta1, and PKC-beta2 failed to influence basal or insulin-stimulated
      glucose transport (2-deoxyglucose uptake) in fibroblasts and adipocytes, despite
      inhibiting insulin effects on glycogen synthesis. In contrast, stable
      overexpression of wild-type PKC-zeta increased, and a dominant-negative mutant
      form of PKC-zeta decreased, basal and insulin-stimulated glucose transport in
      fibroblasts and adipocytes. These findings suggested that: (a) insulin activates
      PKC-zeta, as well as PKC-alpha and beta; and (b) PKC-zeta is required for, and
      may contribute to, insulin effects on glucose transport in 3T3/L1 cells.

PMID- 8999974
TI  - Cloning and characterization of a novel oxidoreductase KDRF from a human bone
      marrow-derived stromal cell line KM-102.
AB  - A cDNA clone coding for a novel oxidoreductase was cloned from a human bone
      marrow-derived stromal cell line KM-102. We screened a cDNA library constructed
      from the mRNA of KM-102 cells stimulated with phorbol 12-myristate 13-acetate and
      calcium ionophore A23187 using a 32P-labeled 15-mer synthetic oligonucleotide (5'
      TAAATAAATAAATAA-3') probe. This probe was designed as a complementary sequence to
      the three reiterated AUUUA sequences, which are contained in the 3'-untranslated
      regions of cytokine and some proto-oncogene mRNAs and correlate with rapid mRNA
      turnover. Then, we obtained one cDNA clone, and further sequence analysis
      revealed that it coded for a new protein exhibiting 30 to approximately 40%
      homology with glutathione reductase. By fusion protein analysis, this protein
      showed reducing activities on 2, 6-dichlorophenol-indophenol and 5,5'-dithio
      bis(2-nitrobenzoic acid) but only a weak reducing activity on oxidized
      glutathione. Although it lacked a stretch of hydrophobic amino acids in its N
      terminus, it was secreted by monkey kidney-derived COS-1 cells when we introduced
      the expression plasmid into them and also secreted by a human lung carcinoma cell
      line A549. Northern blot analysis revealed that the mRNA turnover of this protein
      was regulated by inflammatory stimuli in KM-102 cells. These results show that
      this protein may have scavenging enzyme properties and has its mRNA expression
      regulated in a similar fashion to cytokine genes or proto-oncogenes. Thus, we
      named it KDRF (KM-102-derived reductase-like factor), and KDRF may play a role in
      scavenging reactive oxygen intermediates, which are possibly toxic to cells, in
      response to inflammatory stimuli.

PMID- 8999975
TI  - Human alphaB-crystallin. Small heat shock protein and molecular chaperone.
AB  - The polymerase chain reaction was used to amplify a cDNA sequence encoding the
      human alphaB-crystallin. The amplified cDNA fragment was cloned into the
      bacterial expression vector pMAL-c2 and expressed as a soluble fusion protein
      coupled to maltose-binding protein (MBP). After maltose affinity chromatography
      and cleavage from MBP by Factor Xa, the recombinant human alphaB-crystallin was
      separated from MBP and Factor Xa by anion exchange chromatography. Recombinant
      alphaB-crystallin was characterized by SDS-polyacrylamide electrophoresis (PAGE),
      Western immunoblot analysis, Edman degradation, circular dichroism spectroscopy,
      and size exclusion chromatography. The purified crystallin migrated on SDS-PAGE
      to an apparent molecular weight (Mr approximately 22,000) that corresponded to
      total native human alpha-crystallin and was recognized on Western immunoblots by
      antiserum raised against human alphaB-crystallin purified from lens homogenates.
      Chemical sequencing, circular dichroism spectroscopy, and size exclusion
      chromatography demonstrated that the recombinant crystallin had properties
      similar or identical to its native counterpart. Both recombinant alphaB
      crystallin and MBP-alphaB fusion protein associated to form high molecular weight
      complexes that displayed chaperone-like function by inhibiting the aggregation of
      alcohol dehydrogenase at 37 degrees C and demonstrated the importance of the C
      terminal domain of alphaB-crystallin for chaperone-like activity.

PMID- 8999977
TI  - What is training?

PMID- 8999976
TI  - In the public domain.

PMID- 8999978
TI  - The seven deadly curs'd sins ellipsis Envy.

PMID- 8999994
TI  - Spaced training induces normal long-term memory in CREB mutant mice.
AB  - BACKGROUND: The cAMP responsive element binding protein (CREB) is a transcription
      factor the activity of which is modulated by increases in the intracellular
      levels of cAMP and calcium. Results from studies with Aplysia, Drosophila and
      mice indicate that CREB-activated transcription is required for long-term memory.
      Furthermore, a recent study found that long-term memory for olfactory
      conditioning can be induced with a single trial in transgenic Drosophila
      expressing a CREB activator, whereas in normal flies, with presumably lower CREB
      mediated transcription levels, conditioning requires multiple spaced trials. This
      suggests that CREB-mediated transcription is important in determining the type of
      training required for long-term memory of olfactory conditioning in Drosophila.
      Interestingly, studies with cultured Aplysia neurons indicated that removing a
      CREB repressor promoted the formation of long-term facilitation, a cellular model
      of non-associative memory. RESULTS: Here, we have confirmed that mice lacking the
      alpha and Delta CREB proteins (CREBalphaDelta-) have abnormal long-term, but not
      short-term, memory, as tested in an ethologically meaningful task. Importantly,
      additional spaced training can overcome the profound memory deficits of
      CREBalphaDelta- mutants. Increasing the intertrial interval from 1 to 60 minutes
      overcame the memory deficits of the CREBalphaDelta- mice in three distinct
      behavioral tasks: contextual fear conditioning, spatial learning and socially
      transmitted food preferences. CONCLUSIONS: Previous findings and results
      presented here demonstrate that CREB mutant mice have profound long-term memory
      deficits. Importantly, our findings indicate that manipulations of CREB function
      can affect the number of trials and the intertrial interval required for
      committing information to long-term memory. Remarkably, this effect of CREB
      function is not restricted to simple conditioning tasks, but also affects complex
      behaviours such as spatial memory and memory for socially transmitted food
      preferences.

PMID- 8999995
TI  - Differential effect of components of the extracellular matrix on differentiation
      and apoptosis.
AB  - BACKGROUND: Epithelial cells are closely associated with a basement membrane, but
      the intimate relationships that affect growth, differentiation and survival
      remain enigmatic. We have previously reported that granulosa cells adjacent to
      the basement membrane of the ovarian follicle have a higher degree of
      differentiation compared with cells located distal to the basement membrane. By
      contrast, granulosa cells distal to the basement membrane are the first to
      undergo apoptosis during follicular atresia. Moreover, growth of granulosa cells
      in vitro on a naturally produced basement-membrane-like extracellular matrix
      (ECM) enhances progesterone production and the cellular response to gonadotropic
      hormones by an undefined mechanism. RESULTS: To investigate the effect of the ECM
      on granulosa cell differentiation and death, primary granulosa cells were
      cultured on ECMs that lacked or contained bFGF (basic fibroblast growth factor).
      These otherwise identical ECMs were deposited by HR9 mouse endodermal cells,
      which do not synthesize bFGF, or by HR9 cells transfected with the bFGF gene.
      Both ECMs provided protection against apoptosis in serum-free medium, but only
      the bFGF-containing ECM maintained expression of the steroidogenic P450scc enzyme
      system and the production of progesterone. Moreover, culturing the cells on this
      ECM enhanced the expression of the 30 kDa steroid acute regulatory protein which
      plays a key role in steroid hormone biosynthesis. Laminin, but not fibronectin,
      was able to replace the ECM in protecting the cells from apoptosis; but not in
      maintaining steroidogenesis, whereas bFGF was able to enhance steroidogenesis
      without protecting the cells against apoptosis. Cells cultured on both ECMs or
      laminin had a well-developed actin cytoskeleton compared with cells cultured on
      non-coated dishes, which underwent apoptosis. CONCLUSIONS: Cellular responses to
      ECM are mediated by the combined action of macromolecular constituents and
      regulatory molecules, such as bFGF, that are sequestered and stored in the ECM.
      ECM or laminin protects against cell death by interacting with specific integrin
      receptors and maintaining a well-developed actin cytoskeleton. ECM-bound bFGF
      provides differentiation signals for granulosa cells, which are in intimate
      contact with the ECM. Thus, a clear distinction can be made between the survival
      activity and the differentiation stimulus exerted by the ECM on epithelial cells.

PMID- 8999996
TI  - A requirement for Rho and Cdc42 during cytokinesis in Xenopus embryos.
AB  - BACKGROUND: During cytokinesis in animal cells, an equatorial actomyosin-based
      contractile ring divides the cell into two daughter cells. The position of the
      contractile ring is specified by a signal that emanates from the mitotic spindle.
      This signal has not been identified and it is not understood how the components
      of the contractile ring assemble. It is also unclear how the ring constricts or
      how new plasma membrane inserts specifically behind the leading edge of the
      constricting furrow. The Rho family of small GTPases regulate polarized changes
      in cell growth and cell shape by affecting the formation of actin structures
      beneath the plasma membrane, but their role in cytokinesis is unclear. RESULTS:
      We have studied the function of two Rho family members during the early cell
      divisions of Xenopus embryos by injecting modified forms of Rho and Cdc42. Both
      inhibition and constitutive activation of either GTPase blocked cytokinesis.
      Furrow specification occurred normally, but ingression of the furrow was
      inhibited. Newly inserted cleavage membranes appeared aberrantly on the outer
      surface of the embryo. Microinjected Rho localized to the cortex and regulated
      the levels of cortical F-actin. CONCLUSIONS: These results show that Rho
      regulates the assembly of actin filaments in the cortex during cytokinesis, that
      local activation of Rho is important for proper constriction of the contractile
      furrow, and that Cdc42 plays a role in furrow ingression. Moreover, our
      observations reveal that furrow ingression and membrane insertion are not
      strictly linked. Neither Rho nor Cdc42 appear to be required for establishment of
      the cell-division plane.

PMID- 8999997
TI  - Activin signalling has a necessary function in Xenopus early development.
AB  - The first signalling event in Xenopus development is the mesoderm-forming (or
      Nieuwkoop) induction, starting three hours after fertilization [1]. Two prime
      candidates for the molecule that mediates this signalling are activin [2] and Vg1
      [3], both members of the transforming growth factor beta (TGFbeta) family.
      Because genetic methods are not available for amphibian studies, 'dominant
      negative' truncated receptors have been used in studying signalling molecules
      such as the receptors for fibroblast and platelet-derived growth factors (FGF and
      PDGF) [4] [5]. The truncated receptors bind to, and prevent signalling from,
      endogenous receptors. Activin is a potent mesoderm inducer in vitro, and the
      severe phenotype obtained using a dominant-negative activin receptor in Xenopus
      [6], coupled with evidence from fish [7], suggested that activin is essential for
      development. However, a dominant-negative receptor for activin blocked the
      activity of other TGFbeta family members in Xenopus, most notably Vg1 [8], and
      activin 'knock-out' mice are essentially wild-type in phenotype [7]; these two
      findings cast doubt on the idea of a function for activin in early development.
      We have designed a new receptor construct which can selectively block the
      function of activin but not of Vg1, and we have used it to show that activin has
      an essential role in vivo in Xenopus early development. We conclude that activin,
      or a close relative that has yet to be described, is required for normal
      development.

PMID- 8999998
TI  - R-Ras can activate the phosphoinositide 3-kinase but not the MAP kinase arm of
      the Ras effector pathways.
AB  - BACKGROUND: The small GTPase R-Ras displays a less potent transforming activity
      than the closely related Ras oncogene products. Although R-Ras has been reported
      to interact with c-Raf1 and Ral-GDS in vitro, the pathways by which it exerts its
      effects on cellular proliferation are not known. RESULTS: Both Ras and R-Ras
      interact with phosphoinositide (PI) 3-kinase in vitro, and induce elevation of
      the levels of PI 3-kinase lipid products in intact cells. Unlike Ras, R-Ras does
      not activate Raf or mitogen-activated protein (MAP) kinase in cells. In co
      transfection assays, the serine/threonine protein kinase PKB (or Akt) is
      effectively stimulated by R-Ras, Ras, mutants of Ras that activate PI 3-kinase
      but not other effectors, and activated forms of PI 3-kinase. Ras and R-Ras
      stimulate PKB/Akt through a non-autocrine mechanism that involves PI 3-kinase.
      The constitutive activation of PI 3-kinase alone is sufficient to activate
      PKB/Akt, but not the MAP kinase ERK or the stress-activated protein kinase, Jun N
      terminal kinase. Transformation assays in fibroblasts suggest that PKB/Akt and
      Raf are part of distinct oncogenic signalling pathways. CONCLUSIONS: Both the Raf
      MAP kinase and PI 3-kinase-PKB/Akt pathways are activated by Ras, but only the PI
      3-kinase-PKB/Akt pathway is activated by R-Ras. PI 3-kinase, and downstream
      targets such as PKB/Akt, are likely to be essential mediators of transformation
      induced by R-Ras. PI 3-kinase, as well as Raf, is thus implicated also in Ras
      transformation.

PMID- 8999999
TI  - Cell-cycle arrest and inhibition of Cdk4 activity by small peptides based on the
      carboxy-terminal domain of p21WAF1.
AB  - BACKGROUND: A common event in the development of human neoplasia is the
      inactivation of a damage-inducible cell-cycle checkpoint pathway regulated by
      p53. One approach to the restoration of this pathway is to mimic the activity of
      key downstream effectors. The cyclin-dependent kinase (Cdk) inhibitor p21(WAF1)
      is one such molecule, as it is a major mediator of the p53-dependent growth
      arrest pathway, and can, by itself, mediate growth suppression. The primary
      function of the p21(WAF1) protein appears to be the inhibition of G1 cyclin-Cdk
      complexes. Thus, if we can identify the region(s) of p21(WAF1) that contain its
      inhibitor activity they may provide a template from which to develop novel anti
      proliferative drugs for use in tumours with a defective p53 pathway. RESULTS: We
      report on the discovery of small synthetic peptides based on the sequence of
      p21(WAF1) that bind to and inhibit cyclin D1-Cdk4. The peptides and the full
      length protein are inhibitory at similar concentrations. A 20 amino-acid peptide
      based on the carboxy-terminal domain of p21(WAF1) inhibits Cdk4 activity with a
      concentration for half-maximal inhibition (l0.5) of 46 nM, and it is only four
      fold less active than the full-length protein. The length of the peptide has been
      minimized and key hydrophobic residues forming the inhibitory domain have been
      defined. When introduced into cells, both a 20 amino-acid and truncated eight
      amino-acid peptide blocked phosphorylation of the retinoblastoma protein (pRb)
      and induced a potent G1/S growth arrest. These data support a physiological role
      for the carboxyl terminus of p21(WAF1) in the inhibition of Cdk4 activity.
      CONCLUSIONS: We have discovered that a small peptide is sufficient to mimic
      p21(WAF1) function and inhibit the activity of a critical G1 cyclin-Cdk complex,
      preventing pRb phosphorylation and producing a G1 cell-cycle arrest in tissue
      culture cell systems. This makes cyclin D1-Cdk4 a realistic and exciting target
      for the design of novel synthetic compounds that can act as anti-proliferative
      agents in human cells.

PMID- 9000001
TI  - The agony column.

PMID- 9000000
TI  - Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a
      kinase scaffold protein.
AB  - BACKGROUND: Subcellular targeting of protein kinases and phosphatases provides a
      mechanism for co-localizing these enzymes with their preferred substrates. A
      recently identified mammalian scaffold protein, AKAP79, controls the location of
      two broad-specificity kinases and a phosphatase. RESULTS: We have identified and
      characterized another mammalian scaffold protein which coordinates the location
      of protein kinase A and protein kinase C. We isolated a cDNA encoding a 250 kDa A
      skinase anchoring protein (AKAP) called gravin, which was originally identified
      as a cytoplasmic antigen recognized by myasthenia gravis sera. Sequence homology
      to proteins that are known to bind protein kinase C suggests that gravin also
      binds this kinase. Studies of binding in vitro show that residues 1526-1780 of
      gravin bind the regulatory subunit (RII) of protein kinase A with high affinity,
      and residues 265-556 bind protein kinase C. Gravin expression in human
      erythroleukemia cells can be induced with phorbol ester, resulting in the
      detection of a 250 kDa RII- and PKC-binding protein. Immunolocalization
      experiments show that gravin is concentrated at the cell periphery and is
      enriched in filopodia. Gravin staining is coincident with an AKAP detected by an
      in situ RII-overlay assay, and a PKA-gravin complex can be isolated from human
      erythroleukemia cells. CONCLUSIONS: We present biochemical evidence that gravin
      forms part of a signaling scaffold, and propose that protein kinases A and C may
      participate in the coordination of signal transduction events in the filopodia of
      human erythroleukemia cells.

PMID- 9000003
TI  - Interfacing.

PMID- 9000002
TI  - Don't blame the messenger.

PMID- 9000004
TI  - Pathogenetic tales.

PMID- 9000005
TI  - Deciphering isozyme function: exploring cell biology with chemistry in the post
      genomic era.
AB  - Genome sequencing projects are identifying protein sequences faster than it is
      possible to discover their functions. Fortunately, combinatorial chemistry offers
      an opportunity to develop new biological reagents with which to determine the
      roles of related isozymes.

PMID- 9000006
TI  - Iron transport-mediated drug delivery using mixed-ligand siderophore-beta-lactam
      conjugates.
AB  - BACKGROUND: Assimilation of iron is essential for microbial growth. Most microbes
      synthesize and excrete low molecular weight iron chelators called siderophores to
      sequester and deliver iron by active transport processes. Specific outer membrane
      proteins recognize, bind and initiate transport of species-selective ferric
      siderophore complexes. Organisms most often have specific receptors for multiple
      types of siderophores, presumably to ensure adequate acquisition of the iron that
      is essential for their growth. Conjugation of drugs to synthetic hydroxamate or
      catechol siderophore components can facilitate active iron-transport-mediated
      drug delivery. While resistance to the siderophore-drug conjugates frequently
      occurs by selection of mutants deficient in the corresponding siderophore
      selective outer membrane receptor, the mutants are less able to survive under
      iron-deficient conditions and in vivo. We anticipated that synthesis of mixed
      ligand siderophore-drug conjugates would allow active drug delivery by multiple
      iron receptor recognition and transport processes, further reducing the
      likelihood that resistant mutants would be viable. RESULTS: Mixed ligand
      siderophore-drug conjugates were synthesized by combining hydroxamate and
      catechol components in a single compound that could chelate iron, and that also
      contained a covalent linkage to carbacephalosporins, as representative drugs. The
      new conjugates appear to be assimilated by multiple active iron-transport
      processes both in wild type microbes and in selected mutants that are deficient
      in some outer membrane iron-transport receptors. CONCLUSIONS: The concept of
      active iron-transport-mediated drug delivery can now be extended to drug
      conjugates that can enter the cell through multiple outer membrane receptors.
      Mutants that are resistant to such conjugates should be severely impaired in iron
      uptake, and therefore particularly prone to iron starvation.

PMID- 9000007
TI  - Fluorescent taxoids.
AB  - BACKGROUND: Taxol is a natural product produced by the Pacific Yew, Taxus
      brevifolia, that has emerged as a prominent chemotherapeutic agent for the
      treatment of solid tumors. Taxol's biochemical mode of action has been well
      studied: it binds to microtubules, stabilizing them and preventing their
      depolymerization to tubulin subunits. At lower dosage levels, taxol also
      interferes with the normal dynamics of the tubulin-microtubule equilibrium. This
      biochemical effect causes taxol's ultimate physiological effect, cell cycle
      arrest; taxol is thought to block anaphase A of mitosis. Taxol also causes a
      number of intriguing secondary effects on interphase cells that are poorly
      understood. We believed that a bio-active fluorescent taxol derivative could be a
      useful tool in the study of these cellular mechanisms, especially in interphase
      cells. RESULTS: We have synthesized and characterized a series of stable,
      fluorescently labeled derivatives of taxol that bind to microtubules and have
      cytotoxicities similar to that of taxol. Fluorescence microscopy experiments in
      interphase human foreskin fibroblast (HFF) cells indicate that one of these, a
      sulforhodamine taxoid, is particularly well suited for optical microscopy. The
      use of this taxoid in HFF cells revealed a previously undetected localization of
      taxoids to the nucleolus during interphase. CONCLUSIONS: The production of a new
      fluorescent derivative of taxol provides a useful tool, enabling cellular
      biologists to study taxol's mechanism of action. It is hoped that this material
      will prove particularly useful for the study of taxol's effects upon interphase
      cells. Although in common usage for the last 20 years, Taxol is now a registered
      trademark of Bristol-Myers Squibb. The copyright of Bristol-Myers Squibb is
      recognized when Taxol or taxol is used in this article.

PMID- 9000008
TI  - Structure-function analysis of the cloned opiate receptors: peptide and small
      molecule interactions.
AB  - Opiate receptors mediate the physiological actions of opioid peptides and the
      clinical effects of the synthetic opioid agonists and antagonists. Site-directed
      mutagenesis studies have revealed regions of opiate receptors that are essential
      for ligand recognition, and this could aid the design of more selective opioid
      ligands.

PMID- 9000009
TI  - The leucine zipper domain controls the orientation of AP-1 in the NFAT.AP-1.DNA
      complex.
AB  - BACKGROUND: Heterologous transcription factors bound to adjacent sites in
      eukaryotic promoters often exhibit cooperative behavior. In most instances, the
      molecular basis for this cooperativity is poorly understood. Our efforts have
      been directed toward elucidation of the mechanism of cooperativity between NFAT
      and AP-1, two proteins that coordinately direct expression of the T-cell growth
      factor interleukin-2 (IL-2). RESULTS: We have previously shown that NFAT1 orients
      the two subunits of AP-1, c-Jun and c-Fos, on DNA through direct protein-protein
      interactions. In the present study, we have constructed cJun-cFos chimeric
      proteins and determined their orientation using a novel affinity-cleavage
      technology based on chemical ligation. We find that, in the presence of NFAT, the
      chimeric heterodimer binds in such a way as to preserve the orientation of the AP
      1 leucine zipper, but not that of the basic region. CONCLUSIONS: Protein-protein
      interactions between NFAT and the leucine zipper of AP-1 enable the two proteins
      to bind DNA cooperatively and coordinately regulate the IL-2 promoter. The
      chemical ligation technology presented here provides a powerful strategy for
      affinity cleavage studies, including those using recombinant proteins.

PMID- 9000010
TI  - New loop-loop tertiary interactions in self-splicing introns of subgroup IC and
      ID: a complete 3D model of the Tetrahymena thermophila ribozyme.
AB  - BACKGROUND: Group I introns self-splice via two consecutive trans-esterification
      reactions in the presence of guanosine cofactor and magnesium ions. Comparative
      sequence analysis has established that a catalytic core of about 120 nucleotides
      is conserved in all known group I introns. This core is generally not sufficient
      for activity, however, and most self-splicing group I introns require non
      conserved peripheral elements to stabilize the complete three-dimensional (3D)
      structure. The physico-chemical properties of group I introns make them excellent
      systems for unraveling the structural basis of the RNA-RNA interactions
      responsible for promoting the self-assembly of complex RNAs. RESULTS: We present
      phylogenetic and experimental evidence for the existence of three additional
      tertiary base pairings between hairpin loops within peripheral components of
      subgroup IC1 and ID introns. Each of these new long range interactions, called
      P13, P14 and P16, involves a terminal loop located in domain 2. Although domains
      2 of IC and ID introns share very strong sequence similarity, their terminal
      loops interact with domains 5 and 9 (subgroup IC1) and domain 6 (subgroup ID).
      Based on these tertiary contacts, comparative sequence analysis, and published
      experimental results such as Fe(II)-EDTA protection patterns, we propose 3D
      models for two entire group I introns, the subgroup IC1 intron in the large
      ribosomal precursor RNA of Tetrahymena thermophila and the SdCob.1 subgroup ID
      intron found in the cytochrome b gene of Saccharomyces douglasii. CONCLUSIONS:
      Three-dimensional models of group I introns belonging to four different subgroups
      are now available. They all emphasize the modular and hierarchical organization
      of the architecture of group I introns and the widespread use of base-pairings
      between terminal hairpin loops for stabilizing the folded and active structures
      of large and complex RNA molecules.

PMID- 9000011
TI  - Development of improved tRNAs for in vitro biosynthesis of proteins containing
      unnatural amino acids.
AB  - BACKGROUND: Chemically aminoacylated suppressor tRNAs have previously been used
      in vitro to generate mutant proteins in which unnatural amino acids are
      incorporated site-specifically. Although the existing methodology often provides
      adequate quantities of mutant proteins, the suppression efficiencies of some
      unnatural amino acids are not high enough to yield useful amounts of protein. In
      an effort to make this useful mutagenesis strategy more general, we report here
      the results of a search to find alternative tRNAs as a way of increasing
      suppression efficiencies. RESULTS: Three suppressor tRNAs have been generated by
      runoff transcription and their ability to deliver unnatural amino acids site
      specifically into proteins has been assessed in an E. coli-derived in vitro
      transcription/translation system. Analysis of their ability to insert both polar
      and nonpolar residues in response to an amber codon in two proteins suggests that
      an E. coli tRNAAsn-derived suppressor offers a significant improvement in
      suppression efficiency over other previously used tRNAs. CONCLUSIONS: Use of an
      E. coli tRNAAsn-derived suppressor may provide substantially higher yields of
      proteins containing unnatural amino acids, in addition to offering a broader
      tolerance for polar amino acids. A comparison of suppressor tRNAs derived from
      tRNAAsn, tRNAGln or tRNAAsp with that derived from tRNAPhe supports emerging
      evidence that the identity of an amino acid may be important in message
      recognition.

PMID- 9000012
TI  - In vitro selection of self-cleaving DNAs.
AB  - BACKGROUND: Ribozymes catalyze an important set of chemical transformations in
      metabolism, and 'engineered' ribozymes have been made that catalyze a variety of
      additional reactions. The possibility that catalytic DNAs or 'deoxyribozymes' can
      be made has only recently been addressed. Specifically, it is unclear whether the
      absence of the 2' hydroxyl renders DNA incapable of exhibiting efficient enzyme
      like activity, making it impossible to discover natural or create artificial DNA
      biocatalysts. RESULTS: We report the isolation by in vitro selection of two
      distinct classes of self-cleaving DNAs from a pool of random-sequence
      oligonucleotides. Individual catalysts from 'class I' require both Cu2+ and
      ascorbate to mediate oxidative self-cleavage. Individual catalysts from class II
      use Cu2+ as the sole cofactor. Further optimization of a class II individual by
      in vitro selection yielded new catalytic DNAs that facilitate Cu2+-dependent self
      cleavage with rate enhancements exceeding 1 000 000-fold relative to the
      uncatalyzed rate of DNA cleavage. CONCLUSIONS: Despite the absence of 2'
      hydroxyls, single-stranded DNA can adopt structures that promote divalent-metal
      dependent self-cleavage via an oxidative mechanism. These results suggest that an
      efficient DNA enzyme might be made to cleave DNA in a biological context.

PMID- 9000014
TI  - Genomes and evolution.

PMID- 9000013
TI  - Just add water! The effect of water on the specificity of protein-ligand binding
      sites and its potential application to drug design.
AB  - Recent data have highlighted the enigmatic role that water plays in biomolecular
      complexes. Water at the interface of a complex can increase the promiscuity of an
      interaction, yet it can also provide increased specificity and affinity. The
      ability to engineer water-binding sites into the interface between a drug and its
      target might prove useful in drug design.

PMID- 9000015
TI  - Peptidergic neurohormonal control systems in invertebrates.
AB  - The concerted activity of many neuropeptides has been implicated in the
      neurohormonal control of specific behaviors and various physiological functions
      in some invertebrate model systems. What are the functional consequences of this
      neuropeptide multiplicity? The distinct actions of closely related neuropeptides
      have been detected in molluscs and insects; however, recent work provides
      examples of systems in which some of the multiple isoforms may be functionally
      redundant. Groups of functionally distinct neuropeptides encoded by the same gene
      can be expressed in different neurons by alternative gene splicing or cell
      specific post-translational processing; therefore, as shown recently, they can be
      targeted for release as 'cocktails' to act on specific sets of muscles or
      neurons. One prominent role of neuropeptides is to modulate the activity of
      rhythm-generating circuits, as exemplified by recent research on mollusc neural
      networks, the crab stomatogastric ganglion, and fly circadian pacemakers.

PMID- 9000016
TI  - New concepts of the supplementary motor area.
AB  - The supplementary motor area, although traditionally defined as a single motor
      area, is now viewed as including at least three different areas that can be
      distinguished anatomically and physiologically. The differential use of these
      three areas for various motor behaviors has been the subject of recent studies
      that are beginning to provide novel concepts of the functional differentiation of
      each area.

PMID- 9000017
TI  - Escape behavior - brainstem and spinal cord circuitry and function.
AB  - Recent work has demonstrated that the neural circuits mediating escape reactions
      in lower vertebrates and mammals have a common framework, with only two
      excitatory central synapses in the reflex arc. This relatively direct linkage
      from sense organs to muscles and the fact that segments of the network also
      transmit other motor commands help guarantee that escape always has priority over
      ongoing behaviors. Yet, modulation and plasticity contribute some variability to
      the expression of escape and, therefore, to the adequacy of its survival
      function.

PMID- 9000018
TI  - The superior colliculus and eye movement control.
AB  - Saccade metrics are largely determined by command signals generated in the
      superior colliculus. Recent work has improved our knowledge of the highly complex
      axonal trees that disseminate these signals. It has also demonstrated that
      electrical stimulation of the superior colliculus evokes slow (drifts) as well as
      fast (saccades) eye movements and has provided detailed quantitative descriptions
      of their metrical properties. New biologically influenced models of the superior
      colliculus provide a detailed and realistic account of the discharge of tectal
      pre-saccadic neurons, the properties of evoked saccades and the ability of
      subjects to execute correct saccades in a variety of circumstances.

PMID- 9000019
TI  - Cortical dynamic tuning: the role of intrinsic connections, as revealed by
      modeling.
AB  - A current challenge in computational neuroscience is to elucidate the role of
      cortical circuitry in information processing and in generating motor output. Our
      understanding of the functional significance of specifically organized feedback
      connections is progressing rapidly as researchers establish the equivalence of
      theoretical models to biological neural circuits. Modeling studies of different
      neural structures, along with quantitative comparisons of model performance to
      biological data, have recently helped to identify the basic features of synaptic
      connectivity that may play important roles in cortical operations.

PMID- 9000020
TI  - Interactions between motor commands and somatic perception in sensorimotor
      cortex.
AB  - For many years, it has been postulated that interactions between motor commands
      and somatic perception in the sensorimotor cortices exist, but they have been
      difficult to demonstrate. Recent studies have made demonstration of this
      interaction easier and suggest that cortical activity related to somatic
      sensation and perception is modified by movement-generating mechanisms. Corollary
      discharge and efference copy may also play a role in motor behavior.

PMID- 9000021
TI  - Hemispheric asymmetry of movement.
AB  - Studies in brain-damaged patients indicate that the left hemisphere in right
      handers is specialized for controlling cognitive-motor tasks in both arms. Recent
      functional imaging data support this conclusion, with the finding that
      ipsilateral, as well as contralateral, movements activate the left, but not the
      right, motor cortex or association areas of either hemisphere. Future studies
      must aspire to identify the mechanisms for this asymmetry.

PMID- 9000022
TI  - Synapse maturation and structural plasticity at Drosophila neuromuscular
      junctions.
AB  - The Drosophila larval neuromuscular junction has recently emerged as a powerful
      model system to characterize the cellular and molecular events involved in the
      formation and flexibility of synapses. The combination of molecular, genetic,
      electrophysiological and anatomical approaches has revealed, for example, the
      functional significance of the discs-large gene product (a novel synapse
      organizing protein) in the nervous system. This protein is involved in the
      clustering of at least one ion channel and in the structural modification of
      glutamatergic synapses during target muscle growth. The manipulation of the genes
      encoding ion channels, components of second-messenger cascades, and cell adhesion
      molecules is beginning to tease apart the mechanisms underlying structural
      synaptic plasticity.

PMID- 9000023
TI  - The cerebellum: cortical processing and theory.
AB  - Several advances over the past year have made necessary a complete re-evaluation
      of the function of the cerebellum and of the role of cerebellar synaptic
      plasticity. These advances include the discovery of parallel fiber induced long
      term depression, the presence of normal motor coordination in the absence of
      cerebellar long-term depression in knock-out mice, and the strong activation of
      the cerebellar nuclei while sensory tasks are performed.

PMID- 9000024
TI  - Functions and structures of the motor cortices in humans.
AB  - Humans and non-human primates have several motor areas. Exactly how many is a
      matter of current debate. A proper parcellation of motor areas must be based on
      correlated structural and functional differences. Recent studies indicate that
      the primary motor cortex may be, in reality, two areas (4a and 4p). Similarly,
      there are undoubtedly two or more cingulate motor areas and perhaps two
      supplementary motor areas. The homologies between human and monkey brains are
      striking in some cases, making monkey models of human motor cortices attractive.
      The doctrine of a strict 'homuncular' somatotopical organization of motor areas
      will have to be abandoned. The engagement of motor areas in different types of
      voluntary seems merely a matter of degree of activation rather than exclusive
      specific contributions.

PMID- 9000025
TI  - The neuronal mechanisms of respiratory rhythm generation.
AB  - New, improved in vivo and in vitro approaches have led to a better understanding
      of the mechanisms that generate respiratory rhythm, which depends on a complex
      interaction between network and intrinsic membrane properties. The pre-Botzinger
      complex in the ventrolateral medulla is particularly important for respiratory
      rhythm generation. This complex can be studied in isolation, and it contains all
      the known types of respiratory neurons that are now amenable to detailed cellular
      and molecular analyses.

PMID- 9000027
TI  - Synaptic mechanisms in invertebrate pattern generation.
AB  - Although individual neurons can be intrinsically oscillatory and can be network
      pacemakers, motor patterns are often generated in a more distributed manner.
      Synaptic connections with other neurons are important because they either modify
      the rhythm of the pacemaker cell or are essential for pattern generation in the
      first place. Computational studies of half-center oscillators have made much
      progress in describing how neurons make transitions between active and inactive
      phases in these simple networks. In addition to characterizing phase transitions,
      recent studies have described the synaptic mechanisms that are important for the
      initiation and maintenance of activity in half-center oscillators.

PMID- 9000026
TI  - The representation of temporal information in perception and motor control.
AB  - The representation of temporal information can be examined from both a
      neurological and a computational perspective. Recent evidence suggests that two
      subcortical structures, the cerebellum and basal ganglia, play a critical role in
      the timing of both movement and perception. At a computational level, models of
      an internal clock have been developed in which timing is based on either
      endogenous oscillatory processes or distributed interval-based representations
      derived from relatively slow physiological processes.

PMID- 9000028
TI  - Motor function in microgravity: movement in weightlessness.
AB  - Microgravity provides unique, though experimentally challenging, opportunities to
      study motor control. A traditional research focus has been the effects of linear
      acceleration on vestibular responses to angular acceleration. Evidence is
      accumulating that the high-frequency vestibulo-ocular reflex (VOR) is not
      affected by transitions from a 1 g linear force field to microgravity (<1 g);
      however, it appears that the three-dimensional organization of the VOR is
      dependent on gravitoinertial force levels. Some of the observed effects of
      microgravity on head and arm movement control appear to depend on the previously
      undetected inputs of cervical and brachial proprioception, which change almost
      immediately in response to alterations in background force levels. Recent studies
      of post-flight disturbances of posture and locomotion are revealing sensorimotor
      mechanisms that adjust over periods ranging from hours to weeks.

PMID- 9000029
TI  - Visuomotor functions of the lateral pre-motor cortex.
AB  - Recent studies have provided new insights into the visuomotor functions of the
      dorsal and ventral regions of the lateral pre-motor cortex. Anatomical and
      physiological investigations in non-human primates have demonstrated that these
      regions have differing patterns of cortical connectivity and distinctive neuronal
      responses. Brain-imaging techniques and lesion studies have begun to probe the
      functions of homologous regions in humans.

PMID- 9000030
TI  - Functional and pathophysiological models of the basal ganglia.
AB  - Because of new data, anatomical and functional models of the basal ganglia in
      normal and pathological conditions (e.g. Parkinson's and Huntington's diseases)
      have recently come under greater scrutiny. An update of these models is clearly
      timely, taking into consideration not only changes in neuronal discharge rates,
      but also changes in the patterning and synchronization of neuronal discharge, the
      role of extrastriatal dopamine, and expanded intrinsic and input/output
      connections of these nuclei.

PMID- 9000031
TI  - Neural control.

PMID- 9000033
TI  - Catalysis and regulation.

PMID- 9000032
TI  - Web alert. Neural control.
AB  - A selection of World Wide Web sites relevant to reviews published in this issue
      of Current Opinion in Neurobiology.

PMID- 9000034
TI  - The sophisticated masters of the cell.

PMID- 9000036
TI  - Anti-thyroglobulin autoantibodies in autoimmune thyroid diseases: cross-reactive
      or pathogenic?

PMID- 9000037
TI  - Cerebrospinal fluid interleukin-6 in progressive Neuro-Behcet's syndrome.
AB  - Central nervous system (CNS) involvement in Behcet's disease, usually called
      neuro-Behcet's syndrome (NB), is one of the most serious complications of the
      disease. The present study examined cerebrospinal fluid (CSF) interleukin-6 (IL
      6) activity in patients with NB to explore its relevance to the progressive CNS
      disease. Paired CSF and serum specimens were obtained from 11 patients who were
      diagnosed as having progressive NB based on careful clinical observation and from
      11 patients with active Behcet's disease but lacking progressive CNS disease. IL
      6 levels in the CSF and sera were determined using IL-6-dependent murine
      hybridoma MH60.BSF2 cells. All 11 patients with progressive NB showed marked
      elevation of CSF IL-6 activity [0.18-3.90 U/ml, 1.19 +/- 1.18 (mean +/- SD),
      normal range, <0.010 U/ml]. In contrast, only 5 of the 11 control patients showed
      very modest CSF IL-6 activity below 0.10 U/ml, and CSF IL-6 was not detected in
      the other 6 patients. There was no difference in the serum IL-6 activities of
      patients with progressive NB and control patients. There was no significant
      correlation of CSF IL-6 activity with serum IL-6 activity, CSF cell counts, CSF
      total protein levels, or the CSF/serum albumin quotient. These results indicate
      that persistent chronic CNS inflammation, as evidenced by the enhanced production
      of IL-6 within the CNS, plays an important role in the pathogenesis of
      progressive neuropsychiatric manifestations in Behcet's disease.

PMID- 9000038
TI  - Blocking of TNF-alpha and IL-1 inhibits leukocyte infiltration at early, but not
      at late stage of S. aureus-induced arthritis and the concomitant cartilage
      destruction in rabbits.
AB  - We investigated the involvement of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) in the pathogenesis of heat-killed S. aureus-induced
      arthritis. TNF-alpha and IL-1beta peaked at 2 and 24 hr after the injection,
      respectively. Leukocyte infiltration within 12 hr of the inflammation was
      significantly inhibited (80%) by coinjection of anti-TNF-alpha mAb and IL-1
      receptor antagonist (IL-1Ra) with S. aureus; however, leukocyte infiltration at
      24 hr and thereafter was not inhibited by these agents. The loss of proteoglycan
      in S. aureus-induced arthritis was also unchanged either by anti-TNF-alpha mAb,
      IL-1Ra, or their combination. These results indicate that direct participation of
      TNF-alpha and IL-1 in the pathogenesis of S. aureus-induced arthritis may be
      limited to the early stage of inflammation and blocking of these cytokines did
      not result in diminishing the severity of inflammation. Thus, therapeutic
      approaches with the objective to suppress TNF-alpha and IL-1 may not be effective
      in the clinical treatment of gram-positive bacteria-induced arthritis.

PMID- 9000039
TI  - The human thymic microenvironment during organ culture.
AB  - Cultured human thymic tissue has been transplanted into many patients with T cell
      dysfunction; however, little is known about the effect of in vitro culture on
      thymic tissue. Human postnatal thymic organ cultures were established in vitro to
      study the growth potential of the thymic epithelium and the expression of
      intracellular and surface antigens with time in culture. Marked depletion of bone
      marrow-derived cells was observed within 3 weeks of initiation of organ cultures
      although some viable CD3+ cells could still be detected. Thymic epithelial cells
      in in vitro explants continued to express MHC class I and class II antigens as
      well as cytokeratins. Thymic epithelial cells within cultured thymic organ slices
      maintained their postnatal growth potential, in that cytokeratin-positive
      epithelial monolayers could be established in vitro from these thymic slices up
      to 12 weeks after initiation of organ culture. Thus, thymic explants remained
      viable in culture and could potentially be used to reconstitute immunity in T
      cell deficient patients.

PMID- 9000040
TI  - Steroid 21-hydroxylase autoantibodies in insulin-dependent diabetes mellitus.
      Childhood Diabetes in Finland (DiMe) Study Group.
AB  - We have studied the sera from 304 patients with insulin-dependent diabetes
      mellitus (IDDM) for steroid 21-hydroxylase (P450c21) autoantibodies by an in
      vitro translation and immunoprecipitation assay. Autoantibodies to P450c21 were
      found in 7 patients with IDDM (2.3%). When the IDDM patients with P450c21
      antibodies were analyzed for their HLA, 6 of them (86%) belonged to the HLA
      DQB1*0201-positive group. A strong correlation (r = 0.91, P < 0.001) of
      immunoprecipitation results was observed with adrenocortical autoantibodies
      detected by indirect immunofluorescence, indicating that the adrenal
      autoantibodies in patients with IDDM were anti-P450c21 autoantibodies. The levels
      of P450c21 autoantibodies were significantly higher (P < 0.05) in patients with
      IDDM than in 13 (9 P450c21 autoantibody positive) patients with Addison's
      disease. Although the occurrence of P450c21 antibodies in IDDM was relatively
      low, antibody-positive patients had high antibody levels and may have an ongoing
      subclinical process of adrenal autoimmunity.

PMID- 9000041
TI  - Cell cycle checkpoints and DNA repair in Nijmegen breakage syndrome.
AB  - Nijmegen breakage syndrome is characterized by a variable T cell and B cell
      immunodeficiency, growth failure, and an increased risk of malignancy. It is
      inherited in an autosomal recessive manner and is biochemically related to ataxia
      telangiectasia. Cells from a patient with Nijmegen breakage syndrome were unable
      to arrest cell cycle progression after exposure to ionizing radiation, and BrdU
      incorporation into newly synthesized DNA was uninhibited, demonstrating that
      these cells have an aberrant response to radiation exposure. Although gross
      chromosomal breakage was observed, dinucleotide repeat segments were stable over
      time, suggesting that other types of DNA stability were not affected. DNA-PK
      activity, which is mediated by a protein related to the ataxia-telangiectasia
      gene product and is intimately involved in DNA repair and VDJ recombination, was
      normal in cells from an NBS patient. Therefore, cells from patients with Nijmegen
      breakage syndrome have an abnormal response to radiation exposure similar to that
      seen in ataxia-telangiectasia.

PMID- 9000042
TI  - Immune complexes bound to the primate erythrocyte complement receptor (CR1) via
      anti-CR1 mAbs are cleared simultaneously with loss of CR1 in a concerted reaction
      in a rhesus monkey model.
AB  - In the circulation of primates, C3b-opsonized immune complexes (IC) bound to
      erythrocyte (E) CR1 are taken to the liver and spleen where IC are removed and
      destroyed without lysis or sequestration of E. Individuals with diseases
      associated with IC processing often have decreased E CR1 levels, and in previous
      primate animal models of IC disease, E CR1 was shown to be reduced, but the
      relationship between IC processing and CR1 loss remained to be clarified. We have
      developed a simple model to study this question. In naive (nonimmunized) rhesus
      monkeys, E-bound mouse anti-CR1 mAbs (1500 IgG/E) are not rapidly cleared from
      the circulation. Infusion of monkey anti-mouse IgG leads to rapid indirect
      binding of this second antibody to E CR1. Subsequently, in what appears to be a
      concerted reaction, CR1-bound nascent IC are rapidly cleared from the circulation
      and CR1 is removed from E at the same rate. Clearance of bound IC and loss of CR1
      were both independently followed by RIA. Imaging studies localized the cleared
      anti-CR1 mAbs to the liver. Western blots indicated that the loss of CR1 was not
      due to a conformational change, and E CR1 levels returned to normal in 2-3 weeks,
      suggesting that the return was associated with synthesis of new E. Our findings
      suggest that the key step in the clearance mechanism requires recognition
      (possibly by Fc receptors) of IC-like material associated with E CR1, and this
      leads to loss of CR1 and uptake of the CR1-IC substrate by liver phagocytic
      cells.

PMID- 9000043
TI  - HLA-DR polymorphism modulates the cytokine profile of Mycobacterium leprae HSP
      reactive CD4+ T cells.
AB  - In the present study, in vitro attempts have been made to define the cytokine
      profile of CD4+ T cells from polar leprosy patients and healthy individuals
      against Mycobacterium leprae-derived heat shock proteins (HSPs), HSP65 and HSP18,
      and their trypsin-digested fragments, relating to HLA-DR polymorphism. While all
      tryptic fragments of optimal digestion and undigested HSPs could stimulate CD4+ T
      cells from tuberculoid (TT) leprosy patients and healthy contacts (stimulation
      index, SI > 2.0), only two fragments, TDB65-2 (18 kDa) and TDB18-3 (3 kDa)
      triggered CD4+ T cells of anergic lepromatous (LL) leprosy patients. Both of
      these HSPs and their tryptic fragments showed diverse HLA-DR restriction, with
      DR15 providing the strongest restriction. Cytokine analysis demonstrated that
      HSP65 and HSP18 induced Th1-like activity in the context of all the restricting
      HLA-DR alleles, except DR1 and DR7 which induced a Th2 type of response against
      HSP65 and HSP18, respectively. These Th2 inducer epitopes on HSP65 (DR1
      restricted) and HSP18 (DR7 restricted) were absent from TDB65-2 and TDB18-3 which
      exclusively triggered Th1 cells in both TT and LL forms of leprosy in the context
      of multiple DR alleles, DR15 being the major antigen-presenting allele. These
      studies suggest that the major histocompatibility complex phenotype of the
      antigen-presenting cell can modulate Th1-like versus Th2-like activity against M.
      leprae pathogens in leprosy and healthy individuals.

PMID- 9000044
TI  - Reactivity of a population of armadillo lymphocytes with an antibody to human
      gamma,delta T-cells.
AB  - Reactivity of lymphocytes from the nine-banded armadillo (Dasypus novemcinctus)
      was examined by flow cytometry using a panel of 16 commercially available
      fluorochrome-conjugated monoclonal antibodies raised against human or murine
      leukocyte antigens. The only reactivity observed was with antibody TCRdelta1,
      directed against a common determinant on the delta chain of the human gamma,delta
      T-cell receptor. Using this antibody, a distinct, bright population of
      lymphocytes was seen in the peripheral blood in all of 47 animals examined,
      accounting for 2.0-47.1% of lymphocytes (median, 10.6%). The gamma,delta-reactive
      lymphocyte population comprised a greater percentage of intraepithelial
      lymphocytes in the small intestine than in the blood; variable percentages of
      gamma,delta-reactive cells were also observed in the spleen, thymus, lymph nodes,
      and bone marrow, and in cutaneous lepromas. In armadillos with disseminated
      Mycobacterium leprae infection, a significantly greater percentage of circulating
      lymphocytes reacted with the anti-gamma,delta antibody. This is the first
      described reactivity of armadillo lymphocytes with a monoclonal antibody to a
      lymphocyte antigen, and it may offer a useful tool in disease models involving
      the armadillo.

PMID- 9000045
TI  - Only a subset of trauma patients with depressed mitogen responses have true T
      cell dysfunctions.
AB  - Many studies have demonstrated depressed mitogenic responses in trauma/burn
      patients' peripheral blood mononuclear cells (PBMC). However, data attributing
      the relative contribution of secreted inhibitory factors versus a true T cell
      dysfunction to these depressed mitogenic responses have been conflicting. We have
      characterized the T cell dysfunctions in posttrauma mitogen depression by
      simultaneously assessing patient T cell proliferation in the phytohemagglutinin
      stimulated PBMC and in the purified T cell population induced with anti-CD3 +
      anti-CD4. Patients' samples showed three distinct patterns or progressive phases
      of T cell responses: (i) normal or elevated T cell proliferation in both the
      whole PBMC and the isolated T cell population (phase I); (ii) depressed T cell
      proliferation in the PBMC but normal, or even elevated, proliferation in the
      isolated T cell population (phase II); and (iii) depressed T cell proliferation
      in both the PBMC and the isolated T cell population (phase III). Patients whose T
      cells exhibited only a phase I response experienced no major complications with a
      positive clinical outcome. Patients whose T cell alterations progressed to phase
      II experienced infectious episodes and some complications, but all had positive
      clinical outcomes. In contrast, patients whose T cells progressed to phase III
      dysfunction had severe clinical complications (multiple organ failure), with a
      negative clinical outcome (80% mortality). Patients whose T cells had a phase I
      or phase II response pattern had no true T cell dysfunctions in the absence of
      monocytes. However, patients whose T cells had a true T cell dysfunction (phase
      III) response pattern were at high risk for mortality. Thus, a true T cell
      dysfunction, though occurring in only a minority of trauma patients, is
      predictive of clinical outcome.

PMID- 9000047
TI  - Mouse models of human disease. Part I: techniques and resources for genetic
      analysis in mice.

PMID- 9000046
TI  - Clinical improvement in chronic fatigue syndrome is not associated with
      lymphocyte subsets of function or activation.
AB  - The relationship between markers of immune function and chronic fatigue syndrome
      (CFS) is controversial. To examine the relationship directly, 43 subjects with
      CFS entering a randomized controlled trial of a nonpharmacological treatment for
      CFS gave samples for immunological analysis before and after treatment.
      Percentage levels of total CD3+ T cells, CD4 T cells, CD8 T cells, and activated
      subsets did not differ between CFS subjects and controls. Naive (CD45RA+ RO-) and
      memory (CD45RA- RO+) T cells did not differ between subjects and controls.
      Natural killer cells (CD16+/CD56+/CD3-) were significantly increased in CFS
      patients compared to controls, as was the percentage of CD11b+ CD8 cells. There
      were no correlations between any immune variable and measures of clinical status,
      with the exception of a weak correlation between total CD4 T cells and fatigue.
      There was a positive correlation between memory CD4 and CD8 T cells and
      depression scores and a negative correlation between naive CD4 T cells and
      depression. No immune measures changed during the course of the study, and there
      was no link between clinical improvement as a result of the treatment program and
      immune status. Immune measures did not predict response or lack of response to
      treatment. In conclusion, we have been unable to replicate previous findings of
      immune activation in CFS and unable to find any important associations between
      clinical status, treatment response, and immunological status.

PMID- 9000048
TI  - Mouse models of human disease. Part II: recent progress and future directions.

PMID- 9000049
TI  - Mnt, a novel Max-interacting protein is coexpressed with Myc in proliferating
      cells and mediates repression at Myc binding sites.
AB  - The small constitutively expressed bHLHZip protein Max is known to form sequence
      specific DNA binding heterodimers with members of both the Myc and Mad families
      of bHLHZip proteins. Myc:Max complexes activate transcription, promote
      proliferation, and block terminal differentiation. In contrast, Mad:Max
      heterodimers act as transcriptional repressors, have an antiproliferative effect,
      and are induced upon differentiation in a wide variety of cell types. We have
      identified a novel bHLHZip Max-binding protein, Mnt, which belongs to neither the
      Myc nor the Mad families and which is coexpressed with Myc in a number of
      proliferating cell types. Mnt:Max heterodimers act as transcriptional repressors
      and efficiently suppress Myc-dependent activation from a promoter containing
      proximal CACGTG sites. Transcription repression by Mnt maps to a 13-amino-acid
      amino-terminal region related to the Sin3 interaction domain (SID) of Mad
      proteins. We show that this region of Mnt mediates interaction with mSin3
      corepressor proteins and that its deletion converts Mnt from a repressor to an
      activator. Furthermore, wild-type Mnt suppresses Myc+Ras cotransformation of
      primary cells, whereas Mnt containing a SID deletion cooperates with Ras in the
      absence of Myc to transform cells. This suggests that Mnt and Myc regulate an
      overlapping set of target genes in vivo. When mnt is expressed as a transgene
      under control of the beta-actin promoter in mice the transgenic embryos exhibit a
      delay in development and die during mid-gestation, when c- and N-Myc functions
      are critical. We propose that Mnt:Max:Sin3 complexes normally function to
      restrict Myc:Max activities associated with cell proliferation.

PMID- 9000050
TI  - Suprabasal expression of a dominant-negative RXR alpha mutant in transgenic mouse
      epidermis impairs regulation of gene transcription and basal keratinocyte
      proliferation by RAR-selective retinoids.
AB  - To determine whether 9-cis retinoic acid receptors (RXRs) regulate the biological
      activity of all-trans retinoic acid (tRA) and its receptors (RARs) in skin, we
      have targeted a dominant-negative RXR alpha (dnRXR alpha) lacking transactivation
      function AF-2 to differentiated suprabasal keratinocytes in the epidermis of
      transgenic mice. Driven by the suprabasal-specific keratin-10 gene promoter,
      expression of dnRXR alpha severely reduced the ability of RAR-selective ligands
      tRA and CD367 to induce epidermal mRNA levels of the CRABPII, CRBPI, and CRBPII
      genes, which contain RA-responsive elements (RAREs) DR1 and/or DR2. It also
      reduced gene-specific, synergistic induction of CRBPI mRNA by a combination of
      CD367 and RXR-selective SR11237. Like endogenous RXR alpha, dnRXR alpha in
      epidermal nuclear extracts from the transgenic mice competitively formed
      heterodimers with endogenous RAR gamma on RAREs, suggesting that dnRXR alpha
      impairs retinoid signaling by competing with endogenous RAR gamma-RXR alpha
      heterodimers. Histologically, the epidermis of dnRXR alpha mice showed no
      detectable developmental abnormalities. Surprisingly, in adult animals, the
      suprabasal expression of dnRXR alpha significantly reduced the ability of
      topically applied tRA to stimulate proliferation of undifferentiated
      keratinocytes in the basal layer of epidermis. RXR-selective ligands alone had no
      detectable effects on both normal and transgenic mouse epidermis. Accordingly, we
      suggest that in vivo: (1) in suprabasal keratinocytes, retinoids regulate gene
      transcription via RAR-RXR heterodimers in which RAR confers a predominant ligand
      response, whereas RXR AF-2 is required for liganded RAR AF-2 to efficiently trans
      activate target genes, and (2) this suprabasal RXR-assisted mechanism indirectly
      regulates proliferation of basal keratinocytes likely via intercellular
      signaling.

PMID- 9000051
TI  - Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively
      expressed in endothelial cells.
AB  - Here we describe the cloning and characterization of a PAS domain transcription
      factor termed endothelial PAS-1 (EPAS1). This protein shares 48% sequence
      identity with hypoxia inducible factor (HIF-1alpha) and lesser similarity with
      other members of the basic helix-loop-helix/PAS domain family of transcription
      factors. Like HIF-1alpha, EPAS1 binds to and activates transcription from a DNA
      element originally isolated from the erythropoietin gene and containing the
      sequence 5'-GCCCTACGTGCTGTCTCA-3'. Activation by both HIF-1alpha and EPAS1 is
      stimulated by hypoxic conditions. EPAS1 forms a heterodimeric complex with the
      aryl hydrocarbon nuclear transporter prior to transcriptional activation of
      target genes. EPAS1 expression is limited to the endothelium of mouse embryos
      and, in agreement with its cell type-specific expression pattern, is capable of
      specifically activating the transcription of the endothelial tyrosine kinase gene
      Tie-2. These observations raise the possibility that EPAS1 may represent an
      important regulator of vascularization, perhaps involving the regulation of
      endothelial cell gene expression in response to hypoxia.

PMID- 9000052
TI  - SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin
      in yeast.
AB  - Yeast core telomeric heterochromatin can silence adjacent genes and requires
      RAP1, SIR2, SIR3, and SIR4 and histones H3 and H4 for this telomere position
      effect. SIR3 overproduction can extend the silenced domain. We examine here the
      nature of these multiprotein complexes. SIR2 and SIR4 were immunoprecipitated
      from whole-cell extracts. In addition, using formaldehyde cross-linking we have
      mapped SIR2, SIR4, and RAP1 along telomeric chromatin before and after SIR3
      overexpression. Our data demonstrate that SIR2 and SIR4 interact in a protein
      complex and that SIR2, SIR3, SIR4, and RAP1 map to the same sites along telomeric
      heterochromatin in wild-type cells. However, when overexpressed, SIR3 spreads
      along the chromosome and its interactions are dominant to those of SIR4 and
      especially SIR2, whose detection is decreased in extended heterochromatin. RAP1
      binding at the core region is unaffected by SIR3 overproduction and RAP1 shows no
      evidence of spreading. Thus, we propose that the structure of core telomeric
      heterochromatin differs from that extended by SIR3.

PMID- 9000053
TI  - Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A.
AB  - In the developing eye of Drosophila melanogaster, cells become synchronized in
      the G1 phase of the cell cycle just prior to the onset of cellular
      differentiation and morphogenesis. In roughex (rux) mutants, cells enter S phase
      precociously because of ectopic activation of a Cyclin A/Cdk complex in early G1.
      This leads to defects in cell fate and pattern formation, and results in
      abnormalities in the morphology of the adult eye. A screen for dominant
      suppressors of the rux eye phenotype led to the identification of mutations in
      cyclin A, string (cdc25), and new cell cycle genes. One of these genes, regulator
      of cyclin A (rca1), encodes a novel protein required for both mitotic and meiotic
      cell cycle progression. rca1 mutants arrest in G2 of embryonic cell cycle 16 with
      a phenotype very similar to cyclin A loss of function mutants. Expression of rca1
      transgenes in G1 or in postmitotic neurons promotes Cyclin A protein accumulation
      and drives cells into S phase in a Cyclin A-dependent fashion.

PMID- 9000054
TI  - Meiotic cells monitor the status of the interhomolog recombination complex.
AB  - During meiosis, mutations that cause defects at intermediate stages in the
      recombination process confer arrest at the end of prophase (e.g., pachytene). In
      yeast, mutations of this type include rad50S, dmc1, rad51, and zip1. Rad50 is
      likely part of a recombination initiation complex. DMC1, RAD51, and ZIP1 encode
      two RecA homologs and a synaptonemal complex protein, respectively. We report
      here the effects of mutations in two other (meiosis-specific) genes, RED1 and
      MEK1/MRE4, that encode a chromosome structure component and a protein kinase,
      respectively. A red1 or mek1/mre4 mutation alleviates completely rad50S, dmc1,
      rad51, and zip1 arrest. Furthermore, the red1 and mek1/mre4 mutations define a
      unique, previously unrecognized aspect of recombination imposed very early in the
      process, during DSB formation. Finally, the red1 and mek1/mre4 mutations appear
      to alleviate prophase arrest directly rather than by eliminating, or permitting
      bypass of, the rad50S, dmc1, rad51, or zip1 defects. These and other observations
      suggest that a meiosis-specific regulatory surveillance process monitors the
      status of the protein/DNA interhomolog recombination machinery as an integral
      entity, in its proper chromosomal context, and dependent upon its appropriate
      Red1 and Mek1/Mre4-promoted development. We speculate that a properly developed
      recombination complex emits an inhibitory signal to delay progression of meiotic
      cells out of prophase until or unless the recombination process has progressed,
      at least past certain critical steps, and perhaps to completion.

PMID- 9000055
TI  - Biochemical characterization of a molecular switch involving the heat shock
      protein ClpC, which controls the activity of ComK, the competence transcription
      factor of Bacillus subtilis.
AB  - Development of genetic competence in Bacillus subtilis is controlled by the
      competence-specific transcription factor ComK. ComK activates transcription of
      itself and several other genes required for competence. The activity of ComK is
      controlled by other genes including mecA, clpC, and comS. We have used purified
      ComK, MecA, ClpC, and synthetic ComS to study their interactions and have
      demonstrated the following mechanism for ComK regulation. ClpC, in the presence
      of ATP, forms a ternary complex with MecA and ComK, which prevents ComK from
      binding to its specific DNA target. This complex dissociates when ComS is added,
      liberating active ComK. ClpC and MecA function as a molecular switch, in which
      MecA confers molecular recognition, connecting ClpC to ComK and to ComS.

PMID- 9000056
TI  - The alternative splicing factor PSI regulates P-element third intron splicing in
      vivo.
AB  - Splicing of the Drosophila P-element third intron (IVS3) is inhibited in somatic
      cells, restricting transposase expression to the germ line. Somatic inhibition of
      IVS3 splicing involves the assembly of a multiprotein complex on a regulatory
      sequence in the IVS3 5' exon. The P-element somatic inhibitor protein (PSI) is a
      component of this ribonucleoprotein complex and is required for inhibition of
      IVS3 splicing in vitro. The soma-specific expression pattern of PSI suggests that
      its low abundance in the germ line allows IVS3 splicing. We demonstrate that
      ectopic expression of PSI in the female germ line is sufficient to repress
      splicing of an IVS3 reporter transgene. We also show that IVS3 splicing is
      activated in somatic embryonic cells in the presence of an antisense PSI
      ribozyme. These results support the model that PSI is a tissue-specific regulator
      of IVS3 splicing in vivo.

PMID- 9000058
TI  - A rush to judgement?

PMID- 9000059
TI  - US claims of 'no chemical links' to Gulf War illnesses under fire.

PMID- 9000057
TI  - A human protein required for the second step of pre-mRNA splicing is functionally
      related to a yeast splicing factor.
AB  - We have identified a human splicing factor required for the second step of pre
      mRNA splicing. This new protein, hPrp18, is 30% identical to the yeast splicing
      factor Prp18. In HeLa cell extracts immunodepleted of hPrp18, the second step of
      pre-mRNA splicing is abolished. Splicing activity is restored by the addition of
      recombinant hPrp18, demonstrating that hPrp18 is required for the second step.
      The hPrp18 protein is bound tightly to the spliceosome only during the second
      step of splicing. hPrp18 is required for the splicing of several pre-mRNAs,
      making it the first general second-step splicing factor found in humans. Splicing
      activity can be restored to hPrp18-depleted HeLa cell extracts by yeast Prp18,
      showing that important functional regions of the proteins have been conserved. A
      90-amino-acid region near the carboxyl terminus of hPrp18 is strongly homologous
      to yeast Prp18 and is also conserved in rice and nematodes. The homology
      identifies one region important for the function of both proteins and may define
      a new protein motif. In contrast to yeast Prp18, hPrp18 is not stably associated
      with any of the snRNPs. A 55-kD protein that cross-reacts with antibodies against
      hPrp18 is a constituent of the U4/U6 and U4/U6 x U5 snRNP particles.

PMID- 9000060
TI  - Investment analysts paint rosy prospect for biotech.

PMID- 9000061
TI  - Embryo researcher is sanctioned for using NIH resources.

PMID- 9000062
TI  - Europe seeks to rally regional research.

PMID- 9000063
TI  - Predicting the CJD epidemic in humans.

PMID- 9000064
TI  - Creutzfeld-Jacob disease: Epidemic or false alarm?

PMID- 9000065
TI  - Life on other moons.

PMID- 9000066
TI  - DNA technology: Molecular fish on chips.

PMID- 9000067
TI  - Phosphotransfer hinges in PGK.

PMID- 9000068
TI  - Computation and the single neuron.

PMID- 9000069
TI  - DNA analysis reveals the sex of infanticide victims.

PMID- 9000070
TI  - Medicinal alkaloid as a sex pheromone.

PMID- 9000071
TI  - Glucagon-like peptide-1 and satiety.

PMID- 9000072
TI  - Habitable moons around extrasolar giant planets.
AB  - Possible planetary objects have now been discovered orbiting nine different main
      sequence stars. These companion objects (some of which might actually be brown
      dwarfs) all have a mass at least half that of Jupiter, and are therefore unlikely
      to be hospitable to Earth-like life: jovian planets and brown dwarfs support
      neither a solid nor a liquid surface near which organisms might dwell. Here we
      argue that rocky moons orbiting these companions could be habitable if the planet
      moon system orbits the parent star within the so-called 'habitable zone', where
      life-supporting liquid water could be present. The companions to the stars 16
      Cygni B and 47 Ursae Majoris might satisfy this criterion. Such a moon would,
      however, need to be large enough (>0.12 Earth masses) to retain a substantial and
      long-lived atmosphere, and would also need to possess a strong magnetic field in
      order to prevent its atmosphere from being sputtered away by the constant
      bombardment of energetic ions from the planet's magnetosphere.

PMID- 9000073
TI  - Impaired auditory recognition of fear and anger following bilateral amygdala
      lesions.
AB  - The amygdalar complex is a medial temporal lobe structure in the brain which is
      widely considered to be involved in the neural substrates of emotion. Selective
      bilateral damage to the human amygdala is rare, offering a unique insight into
      its functions. There is impairment of social perception after amygdala damage,
      with defective recognition of facial expressions of emotion. Among the basic
      emotions, the processing of fear and anger has been shown to be disrupted by
      amygdala damage. Although it remains puzzling why this not found in all cases,
      the importance of the amygdala in negative emotion, and especially fear, has been
      confirmed by conditioning, memory and positron emission tomography (PET)
      experiments. Central to our understanding of these findings is the question of
      whether the amygdala is involved specifically in the perception of visual signals
      of emotion emanating from the face, or more widely in the perception of emotion
      in all sensory modalities. We report here a further investigation of one of these
      rare cases, a woman (D.R.) who has impaired perception of the intonation patterns
      that are essential to the perception of vocal affect, despite normal hearing. As
      is the case for recognition of facial expressions, it is recognition of fear and
      anger that is most severely affected in the auditory domain. This shows that the
      amygdala's role in the recognition of certain emotions is not confined to vision,
      which is consistent with its being involved in the appraisal of danger and the
      emotion of fear.

PMID- 9000074
TI  - Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet
      cells.
AB  - The mammalian pancreas is a specialized derivative of the primitive gut endoderm
      and controls many homeostatic functions through the activity of its component
      exocrine acinar and endocrine islet cells. The LIM homeodomain protein ISL1 is
      expressed in all classes of islet cells in the adult and its expression in the
      embryo is initiated soon after the islet cells have left the cell cycle. ISL1 is
      also expressed in mesenchymal cells that surround the dorsal but not ventral
      evagination of the gut endoderm, which together comprise the pancreatic anlagen.
      To define the role of ISL1 in the development of the pancreas, we have now
      analysed acinar and islet cell differentiation in mice deficient in ISL1
      function. Dorsal pancreatic mesenchyme does not form in ISL1-mutant embryos and
      there is an associated failure of exocrine cell differentiation in the dorsal but
      not the ventral pancreas. There is also a complete loss of differentiated islet
      cells. Exocrine, but not endocrine, cell differentiation in the dorsal pancreas
      can be rescued in vitro by provision of mesenchyme derived from wild-type
      embryos. These results indicate that ISL1, by virtue of its requirement for the
      formation of dorsal mesenchyme, is necessary for the development of the dorsal
      exocrine pancreas, and also that ISL1 function in pancreatic endodermal cells is
      required for the generation of all endocrine islet cells.

PMID- 9000075
TI  - Distinct functions of nuclear and cytoplasmic calcium in the control of gene
      expression.
AB  - Calcium entry into neuronal cells through voltage or ligand-gated ion channels
      triggers neuronal activity-dependent gene expression critical for adaptive
      changes in the nervous system. Cytoplasmic calcium transients are often
      accompanied by an increase in the concentration of nuclear calcium, but the
      functional significance of such spatially distinct calcium signals is unknown.
      Here we show that gene expression is differentially controlled by nuclear and
      cytoplasmic calcium signals which enable a single second messenger to generate
      diverse transcriptional responses. We used nuclear microinjection of a non
      diffusible calcium chelator to block increases in nuclear, but not cytoplasmic,
      calcium concentrations following activation of L-type voltage-gated calcium
      channels. We showed that increases in nuclear calcium concentration control
      calcium-activated gene expression mediated by the cyclic-AMP-response element
      (CRE), and demonstrated that the CRE-binding protein CREB can function as a
      nuclear calcium-responsive transcription factor. A second signalling pathway,
      activating transcription through the serum-response element (SRE), is triggered
      by a rise in cytoplasmic calcium and does not require an increase in nuclear
      calcium.

PMID- 9000076
TI  - Actin polymerization is induced by Arp2/3 protein complex at the surface of
      Listeria monocytogenes.
AB  - The pathogenic bacterium Listeria monocytogenes is capable of directed movement
      within the cytoplasm of infected host cells. Propulsion is thought to be driven
      by actin polymerization at the bacterial cell surface, and moving bacteria leave
      in their wake a tail of actin filaments. Determining the mechanism by which L.
      monocytogenes polymerizes actin may aid the understanding of how actin
      polymerization is controlled in the cell. Actin assembly by L. monocytogenes
      requires the bacterial surface protein ActA and protein components present in
      host cell cytoplasm. We have purified an eight-polypeptide complex that possesses
      the properties of the host-cell actin polymerization factor. The pure complex is
      sufficient to initiate ActA-dependent actin polymerization at the surface of L.
      monocytogenes, and is required to mediate actin tail formation and motility. Two
      subunits of this protein complex are actin-related proteins (ARPs) belonging to
      the Arp2 and Arp3 subfamilies. The Arp3 subunit localizes to the surface of
      stationary bacteria and the tails of motile bacteria in tissue culture cells
      infected with L. monocytogenes; this is consistent with a role for the complex in
      promoting actin assembly in vivo. The activity and subunit composition of the
      Arp2/3 complex suggests that it forms a template that nucleates actin
      polymerization.

PMID- 9000077
TI  - Extension of chromatin accessibility by nuclear matrix attachment regions.
AB  - Transcription of the variable region of the rearranged immunoglobulin mu gene is
      dependent on an enhancer sequence situated within one of the introns of the gene.
      Experiments with transgenic mice have shown that activation of the promoter
      controlling this transcription also requires the matrix-attachment regions (MARs)
      that flank the intronic enhancer. As this mu gene enhancer can establish local
      areas of accessible chromatin, we investigated whether the MARs can extend
      accessibility to more distal positions. We eliminated interactions between
      enhancer- and promoter-bound factors by linking mu enhancer/MAR fragments to the
      binding sites for bacteriophage RNA polymerases that were either close to or one
      kilobase distal to the enhancer. The mu enhancer alone mediated chromatin
      accessibility at the proximal site but required a flanking MAR to confer
      accessibility upon the distal promoter. This long-range accessibility correlates
      with extended demethylation of the gene construct but not with whether it is
      being actively transcribed. MARs thus collaborate with the mu enhancer to
      generate an extended domain of accessible chromatin.

PMID- 9000078
TI  - NMR structure of inactivation gates from mammalian voltage-dependent potassium
      channels.
AB  - The electrical signalling properties of neurons originate largely from the gating
      properties of their ion channels. N-type inactivation of voltage-gated potassium
      (Kv) channels is the best-understood gating transition in ion channels, and
      occurs by a 'ball-and-chain' type mechanism. In this mechanism an N-terminal
      domain (inactivation gate), which is tethered to the cytoplasmic side of the
      channel protein by a protease-cleavable chain, binds to its receptor at the inner
      vestibule of the channel, thereby physically blocking the pore. Even when
      synthesized as a peptide, ball domains restore inactivation in Kv channels whose
      inactivation domains have been deleted. Using high-resolution nuclear magnetic
      resonance (NMR) spectroscopy, we analysed the three-dimensional structure of the
      ball peptides from two rapidly inactivating mammalian K. channels (Raw3 (Kv3.4)
      and RCK4 (Kv1.4)). The inactivation peptide of Raw3 (Raw3-IP) has a compact
      structure that exposes two phosphorylation sites and allows the formation of an
      intramolecular disulphide bridge between two spatially close cysteine residues.
      Raw3-IP exhibits a characteristic surface charge pattern with a positively
      charged, a hydrophobic, and a negatively charged region. The RCK4 inactivation
      peptide (RCK4-IP) shows a similar spatial distribution of charged and uncharged
      regions, but is more flexible and less ordered in its amino-terminal part.

PMID- 9000079
TI  - Synergistic effects of substrate-induced conformational changes in
      phosphoglycerate kinase activation.
AB  - Phosphoglycerate kinase (PGK), a key enzyme in glycolysis, catalyses the transfer
      of a phosphoryl-group from 1,3-bisphosphoglycerate to ADP to form 3
      phosphoglycerate and ATP. Despite extensive kinetic and structural investigations
      over more than two decades, the conformation assumed by this enzyme during
      catalysis remained unknown. Here we present the 2.8 A crystal structure of a
      ternary complex of PGK from Trypanosoma brucei, the causative agent of sleeping
      sickness. This structure determination relied on a procedure in which fragments
      containing less than 10% of the scattering mass were successively positioned in
      the unit cell to obtain phases. The PGK ternary complex exhibits a dramatic
      closing of the large cleft between the two domains seen in all previous studies,
      thereby bringing the two ligands, 3-phosphoglycerate and ADP into close
      proximity. Our results demonstrate that PGK is a hinge-bending enzyme, reveal a
      novel mechanism in which substrate-induced effects combine synergistically to
      induce major conformational changes and, to our knowledge, afford the first
      observation of the PGK active site in a catalytic conformation.

PMID- 9000080
TI  - Variation on a theme of Creutzfeldt-Jakob disease: implications of new cases with
      a young age at onset.

PMID- 9000081
TI  - Biological consequences of human immunodeficiency virus type 1 envelope
      polymorphism: does variation matter? 1995 Fleming Lecture.

PMID- 9000082
TI  - A novel neutralization epitope on the 'thumb' subdomain of human immunodeficiency
      virus type 1 reverse transcriptase revealed by a monoclonal antibody.
AB  - We have prepared a MAb, 7C4, which inhibits the RNA-dependent DNA polymerase
      activity of human immunodeficiency virus type 1 (HIV- 1) reverse transcriptase
      (RT); this MAb has allowed identification of a previously unknown neutralizing
      epitope of RT. Analysis of the epitope and of the mechanism of polymerase
      inhibition revealed that 7C4 acts by interfering with the interaction between RT
      and the template-primer. 7C4 recognizes a discontinuous epitope on the two alpha
      helices, alphaH and alpha(I), that make up the 'thumb' subdomain of RT. The
      existing crystallographic model of HIV-1 RT suggests that the 'thumb' subdomain,
      together with the 'fingers' and 'palm', form a nucleic-acid-binding cleft in the
      66 kDa subunit of RT and that alphaH is in contact with the primer strand of the
      template-primer. The extent of inhibition of enzyme activity produced by 7C4
      correlates with the reported primer-length-dependency of template-primer binding
      to RT. Inhibition by 7C4 was competitive with respect to the template-primer and
      mixed with respect to the substrate. Binding of 7C4 to RT was prevented by
      preincubation of the enzyme with high concentrations of template-primer but not
      with substrate. Thus, the 7C4 epitope apparently exists on part of the template
      primer binding site of the alphaH and alpha(I) regions of the 'thumb' subdomain.
      This neutralization epitope is a logical target for the development of new types
      of HIV-1 RT inhibitors.

PMID- 9000083
TI  - Two neutralizing anti-V3 monoclonal antibodies act by affecting different
      functions of human immunodeficiency virus type 1.
AB  - Monoclonal antibody (MAb) ICR41.1i (rat IgG2a) is specific for a conformation
      dependent epitope of human immunodeficiency virus type 1 (HIV-1) V3 , and MAb F58
      (mouse IgG1) recognizes the peptide IXXGPGR, at the tip of the V3 loop. Both MAbs
      neutralized HIV-1 strain IIIB in C8166 and HeLa-T4(CD4) cells. Neutralization by
      either MAb did not inhibit attachment of virus to target cells as determined by
      FACS analysis, ELISA or immunofluorescence, and such attachment was absolutely
      dependent on the availability of CD4 molecules. F58 inhibited virus-induced cell
      cell fusion, and reduced internalization of virions in direct proportion to
      neutralization. In contrast, ICR41.li had no effect on HIV-1-mediated cell fusion
      or on internalization of virus. It was concluded that MAb F58 neutralized
      infectivity by inhibiting fusion of the virus with the cell and internalization
      of the viral core, and that ICR41.1i neutralized by inhibiting a post-fusion
      internalization event. The possible mechanism by which a neutralizing antibody
      binds to the V3 loop and affects the function(s) of structures inside the virion
      is discussed. Lastly, postattachment neutralization (PAN) was investigated. F58
      mediated PAN at 21 degrees C and 35 degrees C. However, ICR41.1i gave PAN at 21
      degrees C but not at 35 degrees C, suggesting that a temperature-dependent event
      affecting the V3 loop had abrogated neutralization. Overall, it appears that
      antibodies to different epitopes within the V3 loop neutralize by affecting very
      different functions of the virus.

PMID- 9000084
TI  - In vitro cytocidal effects of human immunodeficiency virus type 1 Nef on unprimed
      human CD4+ T cells without MHC restriction.
AB  - We have previously shown that the C-terminal region of human immunodeficiency
      virus type 1 (HIV-1) Nef antigen present on the outer surface of virus-infected
      cells has an affinity for uninfected T cells and that the Nef protein is
      responsible for T cell death. To exclude completely the possibility of MHC
      restriction of this cytotoxic activity, the in vitro cytotoxic potential of HIV-1
      Nef against various CD4+ T cell lines as well as naive T lymphocytes was
      investigated using a baculovirus expression system. Insect cells expressing
      myristoylated Nef on their cell surface were shown to kill a proportion of CD4+ T
      cells within 8 h. However, N-terminal truncated and unmyristoylated Nef proteins
      were not present on the outer surface of insect cell membranes and failed to show
      any killing activity. Monoclonal antibodies against the C-terminal region of Nef
      inhibited cytolysis. Thus, we conclude that specific Nef-mediated cytolysis is
      induced by contact with unprimed CD4+ T lymphocytes without MHC restriction.

PMID- 9000086
TI  - Effect of cyclosporin A on the replication cycle of human immunodeficiency virus
      type 1 derived from H9 and Molt-4 producer cells.
AB  - The effect of cyclosporin A (CsA) on the replication of human immunodeficiency
      virus type 1 (HIV-1) was studied. CsA treatment inhibited virus production in
      chronically infected H9 and Molt-4 cells. CsA treatment of HeLaCD4-LTR/beta-gal
      cells or extracellular viruses also inhibited infection (IC50 1 microg/ml). The
      intracellular CsA-binding molecule cyclophilin A was detected in HIV-1 derived
      from chronically infected H9 cells, but it was present at a substantially lower
      level in HIV-1 derived from chronically infected Molt-4 cells. The low level of
      cyclophilin A in viral particles derived from Molt-4 cells correlated well with
      their substantially lower infectivity as assayed on HeLaCD4-LTR beta-gal cells.
      CsA treatment of infected cells showed a dose-dependent reduction of cyclophilin
      A incorporation into virions; the amount of cyclophilin A incorporation was found
      to be dependent on the producer cell type.

PMID- 9000085
TI  - CD8+ cells from asymptomatic human immunodeficiency virus-infected individuals
      suppress superinfection of their peripheral blood mononuclear cells.
AB  - Most human immunodeficiency virus (HIV)-infected individuals show evidence of
      infection by only one strain of the virus despite possible frequent contact with
      multiple strains. The reason(s) for the emergence of a dominant strain of virus
      in HIV-infected people and the mechanism(s) which prevent other strains from
      establishing an infection is not known. In the present study, we demonstrate that
      peripheral blood mononuclear cells (PBMC) of asymptomatic HIV-infected
      individuals can resist productive infection by HIV-1 and HIV-2 strains. Although
      the PBMC of these individuals are resistant to superinfection, their CD4+ cells
      are susceptible to infection. Moreover, two weeks after infection of their PBMC
      in culture, the superinfecting virus can be recovered from isolated CD4+ cells.
      When CD8+ cells from asymptomatic individuals are added to the superinfected CD4+
      cells, replication of the exogenously introduced virus is inhibited. In contrast,
      PBMC from individuals who have progressed to disease (Progressors) do not resist
      superinfection and their CD8+ cells do not showthe antiviral activity which
      controls productive HIV infection. These findings suggest that CD8+ cells
      suppressing HIV replication in infected individuals may be critical in preventing
      the establishment of infection by other strains of HIV by blocking virus
      replication.

PMID- 9000087
TI  - Rapid development of vaccine protection in macaques by live-attenuated simian
      immunodeficiency virus.
AB  - Convincing data on experimental vaccines against AIDS have been obtained in the
      simian immunodeficiency virus (SIV) macaque model by preinfection with a virus
      attenuated by a nef deletion. To investigate the efficacy of a nef deletion
      mutant of SIVmac32H called pC8 as a live-attenuated vaccine after shorter
      preinfection periods and to learn more about the nature of the immune protection
      induced, eight rhesus monkeys were infected intravenously with the pC8 virus. All
      monkeys became persistently infected, exhibiting low cell-associated viral loads,
      but strong cellular and, in terms of binding antibodies, strong humoral antiviral
      responses. Two of eight pC8-infected monkeys developed an immunodeficiency and
      were not challenged. Sequence analysis of their nef revealed complete
      replenishment of the deletion. The other six monkeys, two preinfected for 42
      weeks and four for 22 weeks, were challenged with pathogenic spleen-derived SIV.
      Complete protection was achieved in four vaccinees. Virus was consistently
      detected in two vaccinees from the 22-week-group challenge, however, they
      remained clinically healthy over a prolonged period. Protection from challenge
      virus infection or a delayed disease development seemed to be associated with a
      sustained SIV-specific T helper cell response after challenge. Thus, a
      sterilizing immunity against superinfection with pathogenic SIV can be induced
      even after a relatively short waiting period of 22 weeks. Nevertheless, such a
      vaccine raises severe safety concerns because of its potential to revert to
      virulence.

PMID- 9000090
TI  - Sequence analysis and transcriptional activity of the LTR of OLV-CU1, a North
      American ovine lentivirus.
AB  - Although ovine lentiviruses have been described in the United States since the
      early part of this century, North American strains of sheep lentiviruses remain
      relatively uncharacterized at the molecular level. The LTR of a North American
      ovine lentivirus, OLV-CU1, was found to be closely related at the molecular and
      functional levels to visna virus, the Icelandic ovine lentivirus. Sequence
      analysis of the LTR revealed high identity to other ovine and caprine
      lentiviruses in key regulatory elements of the upstream promoter region (-25 to 
      115). However, the R region of the LTR was much less homologous. Transcriptional
      control of OLV-CU1 in transient transcriptional assays required a conserved
      putative AP-4 region and possibly an AP-1 like element in the upstream promoter
      region for moderate to high levels of transcription, much like visna virus. In
      contrast to visna virus, the downstream region beyond the transcriptional start
      site was required for virus-specific transactivation.

PMID- 9000088
TI  - Regulation of human endogenous retrovirus-K Gag expression in teratocarcinoma
      cell lines and human tumours.
AB  - Human endogenous retrovirus-K (HERV-K) Gag protein is produced by both Tera 1 and
      PA-1 (ovarian teratocarcinoma) cells, but only Tera 1 cells release the protein
      in the form of particles. It was unclear how Gag production was regulated in
      these cell types. Although both Tera 1 and PA-1 cells express Gag, demethylation
      upon treatment with 5-azacytidine (5-AZC) or exposure to the chromatin-modifying
      agent n-butyrate resulted in an increase in Gag protein levels only in Tera 1
      cells. Consistent with this cell type-specific overexpression of Gag in response
      to demethylation, exposure to 5-AZC caused undermethylation of the gag gene and
      adjacent 5'LTR only in Tera 1 but not PA-1 or Raji cells. Similarly and
      importantly, undermethylation of gag sequences and expression of Gag were also
      correlated in primary human testicular tumours. These results therefore suggest
      that endogenous retroviral elements are subject to regulation through the
      methylation of CpG dinucleotides.

PMID- 9000089
TI  - Jaagsiekte retrovirus establishes a disseminated infection of the lymphoid
      tissues of sheep affected by pulmonary adenomatosis.
AB  - Jaagsiekte retrovirus (JSRV) is an exogenous type D-related retrovirus
      specifically associated with a contagious lung cancer of sheep (sheep pulmonary
      adenomatosis; SPA). Recently, epithelial tumour cells in the lungs of SPA
      affected sheep were identified as major sites of JSRV replication by
      immunological techniques and RT-PCR amplification of part of JSRV gag. JSRV was
      not detected outside the lungs and their draining lymph nodes. However, low
      levels of JSRV expression in non-respiratory tissues could have been masked by co
      amplification of endogenous JSRV-related sequences, which were differentiated
      from JSRV by the lack of a Scal restriction site in the PCR product. To further
      investigate the pathogenesis of SPA, an exogenous virus-specific hemi-nested PCR
      was developed utilizing primers in the U3 region of JSRV LTR, where major
      differences between endogenous and exogenous sequences exist. This technique was
      shown to be > or = 10(5)-fold more sensitive than the previous gag PCR/ScaI
      digestion method. Using this new assay the tissue distribution of JSRV in sheep
      with natural and experimentally induced SPA was analysed. Proviral DNA and JSRV
      transcripts were found in all tumours and lung secretions of SPA-affected sheep
      (n = 22) and in several lymphoid tissues. The mediastinal lymph nodes draining
      the lungs were consistently demonstrated to be infected by JSRV (10/10). JSRV
      transcripts were also detected in spleen (7/9), thymus (2/4), bone marrow (4/8)
      and peripheral blood mononuclear cells (3/7). Proviral DNA was also detected in
      these tissues although in a much lower proportion of cases. JSRV was not detected
      in 27 samples from unaffected control animals (n = 15).

PMID- 9000092
TI  - Evolutionary analysis of variants of hepatitis C virus found in South-East Asia:
      comparison with classifications based upon sequence similarity.
AB  - Variants of hepatitis C virus (HCV) have been classified by nucleotide sequence
      comparisons in different regions of the genome. Many investigators have defined
      the ranges of sequence similarity values or evolutionary distances corresponding
      to divisions of HCV into types, subtypes and isolates. Using these criteria,
      novel variants of HCV from Vietnam, Thailand and Indonesia have been classified
      as types 7, 8, 9, 10 and 11, many of which can be further subdivided into between
      two to four subtypes. In this study, this distance-based method of virus
      classification was compared with phylogenetic analysis and statistical measures
      to establish the confidence of the groupings. Using bootstrap resampling of
      phylogenetic trees in several subgenomic regions (core, E1, NS5) and with
      complete genomic sequences, we found that one set of novel HCV variants ('types
      7, 8, 9 and 11') consistently grouped together into a single clade that also
      contained type 6a, while 'type 10a' grouped with type 3. In contrast, no robust
      higher-order groupings were observed between any of the other five previously
      described HCV genotypes (types 1-5). In each subgenomic region, the distribution
      of pairwise distances between members of the type 6 clade were consistently bi
      modal and therefore provided no justification for classification of these
      variants into the three proposed categories (type, subtype, isolate). Based on
      these results, we propose that a more useful classification would regard all
      these variants as subtypes of type 6 or type 3, even though the level of sequence
      diversity within the clade was greater than observed for other genotypes.
      Classification by phylogenetic relatedness rules out simple sequence similarity
      measurements as a method for assigning HCV genotypes, but provides a more
      appropriate description of the evolutionary and epidemiological history of a
      virus.

PMID- 9000091
TI  - Trojan Horse macrophages: studies with the murine lactate dehydrogenase-elevating
      virus and implications for sexually transmitted virus infection.
AB  - Previous studies have suggested that monocytes or macrophages may mediate
      internal virus spread. For the present study, the tissue distribution and
      infectious potential of dye-labelled and/or lactate dehydrogenase-elevating virus
      (LDV)-infected murine macrophages were determined. Murine peritoneal macrophages
      were labelled with the fluorescent carbocyanine tracking dye Dil, injected into
      mice, and the tissue distribution of Dil-labelled cells was determined by
      fluorescence analysis of frozen sections. Mice receiving intravenous (i.v.) or
      intraperitoneal injections of Dil-labelled macrophages displayed rapid and broad
      tissue distribution of the labelled cells. Intravaginal injection of Dil-labelled
      macrophages resulted in penetration into the placentas, but not the fetuses, of
      pregnant mice. When macrophages were LDV-infected and Dil-labelled prior to i.v.
      injection into pregnant mice, they homed to various tissues including the
      placenta, but were not found in fetuses. Intravaginal injection of LDV-infected
      macrophages resulted in systemic LDV infection, even though the free-virus dose
      was less than the minimum infectious dose by this route. Neither polyclonal nor
      monoclonal IgG anti-LDV antibodies protected mice from vaginal infection with
      cell-associated virus, and LDV-immune complexes were themselves infectious by the
      vaginal route. These results show that exogenous macrophages are widely
      distributed following parenteral injection, penetrate locally to placentas after
      intravaginal injection, and are capable of acting vaginally as relatively
      efficient virus infection-delivery vehicles. Thus, 'Trojan Horse' macrophages are
      potentially infectious vehicles both for internal virus spread and for animal-to
      animal transmission.

PMID- 9000093
TI  - Low pH-induced pore formation by spike proteins of enveloped viruses.
AB  - Exposure of Aedes albopictus cells infected with Semliki Forest virus (SFV;
      Togaviridae) to mildly acidic pH (5.6) results in a dramatic increase in the host
      cell membrane permeability due to pore formation by the virus spike proteins.
      Identical results were obtained when the cells were infected with two other
      viruses, Sindbis virus (SIN, Togaviridae) and vesicular stomatitis virus (VSV,
      Rhabdoviridae). This permeability change could also be observed on isolated
      virions of SFV, SIN and VSV by measuring the influx of propidium iodide, a
      nucleic acid-specific fluorescent marker, into the virions. This influx was
      dependent on the presence of the ectodomains of the viral spikes and could be
      hampered by zinc ions. Furthermore, haemagglutinin, a membrane protein of
      influenza A virus (Orthomyxoviridae), expressed in Aedes cells induced a change
      in membrane permeability identical to that induced by the spike proteins of SFV,
      SIN and VSV when exposed to low pH. Thus acid-induced membrane permeability
      changes produced by spike proteins of three different virus families could be
      demonstrated in infected cells as well as in virions. Therefore, the low pH
      induced pore formation by viral spike proteins seems to be more than an event
      specific for togaviruses and might well be an inherent property of enveloped
      viruses that use the endocytotic pathway to infect a cell.

PMID- 9000094
TI  - Mapping the neutralizing epitopes on the glycoprotein of infectious
      haematopoietic necrosis virus, a fish rhabdovirus.
AB  - Twelve neutralizing monoclonal antibodies (MAbs) against the fish rhabdovirus,
      infectious haematopoietic necrosis virus (IHNV), were used to select 20 MAb
      escape mutants. The nucleotide sequence of the entire glycoprotein (G) gene was
      determined for six mutants representing differing cross-neutralization patterns
      and each had a single nucleotide change leading to a single amino acid
      substitution within one of three regions of the protein. These data were used to
      design nested PCR primers to amplify portions of the G gene of the 14 remaining
      mutants. When the PCR products from these mutants were sequenced, they also had
      single nucleotide substitutions coding for amino acid substitutions at the same,
      or nearby, locations. Of the 20 mutants for which all or part of the glycoprotein
      gene was sequenced, two MAbs selected mutants with substitutions at amino acids
      230-231 (antigenic site I) and the remaining MAbs selected mutants with
      substitutions at amino acids 272-276 (antigenic site II). Two MAbs that selected
      mutants mapping to amino acids 272-276, selected other mutants that mapped to
      amino acids 78-81, raising the possibility that this portion of the N terminus of
      the protein was part of a discontinuous epitope defining antigenic site II.
      CLUSTAL alignment of the glycoproteins of rabies virus, vesicular stomatitis
      virus and IHNV revealed similarities in the location of the neutralizing epitopes
      and a high degree of conservation among cysteine residues, indicating that the
      glycoproteins of three different genera of animal rhabdoviruses may share a
      similar three-dimensional structure in spite of extensive sequence divergence.

PMID- 9000095
TI  - The genome sequence of the virulent Kabete 'O' strain of rinderpest virus:
      comparison with the derived vaccine.
AB  - We have compared the complete genome sequences of the vaccine strain of
      rinderpest virus and the virulent strain from which it was derived. Only 87 bases
      differed between the two genomes (0.55%). Possibly significant differences in
      amino acid sequence were found in the N, P, F, H and L proteins. A number of
      differences were also found in the leader region (3' end of the genome), whilst
      the trailer region appears to be more conserved. In addition, the length of the
      genome was found in both cases to be 15882, an exact multiple of six, fulfilling
      predictions made earlier based on work with Sendai and measles viruses.

PMID- 9000096
TI  - Nucleotide sequence of the gene encoding the viral polymerase of avian
      pneumovirus.
AB  - We report here the nucleotide sequence of the L gene of avian pneumovirus (APV).
      This is the second pneumovirus L gene and the second avian paramyxovirus L gene,
      following that of Newcastle disease virus, to be sequenced. The APV L gene is
      6099 nucleotides long and encodes a single large ORF of 2004 amino acids. This
      makes the APV L protein the smallest to be described for any nonsegmented,
      negative-strand RNA virus. The protein contains six linear non-contiguous
      domains, a putative ATP-binding site and four polymerase motifs previously
      described for the L proteins of negative-strand RNA viruses. Phylogenetic
      analysis of domain III of 14 different L proteins suggests the pneumoviruses to
      be as distant in evolutionary terms from the other members of the Paramyxoviridae
      as are the Filoviridae.

PMID- 9000097
TI  - Persistent infection of mammalian cells by Rift Valley fever virus.
AB  - Infection of mammalian cells with Rift Valley fever virus (RVFV) leads generally
      to the production of virus and cell death. In this paper we examined the fate of
      Vero cells infected with three strains of RVFV and observed that, while a large
      proportion of cells exhibited a clear cytopathic effect (CPE), a small but
      significant fraction did not undergo a lytic infection but was able to
      proliferate and establish a persistent infection. Several independent RVFV
      persistently infected cell lines have been established and passaged for more than
      1 year after infection with a virulent strain (ZH548) and two attenuated strains
      (C13 and MP12). Although the viruses used for the primary infection were plaque
      purified, we do not know whether defective-interfering particles were responsible
      for the establishment of the persistent infection. The persistently infected
      cells became resistant to superinfection with RVFV but not with other viruses and
      shed low amounts of infectious, lytic and non-lytic virus during a limited number
      of passages. In all the passages tested, the three genomic segments or related
      products were synthesized as well as the structural nucleoprotein N and
      glycoproteins G1 and G2. Abnormal defective RNAs were detected, migrating faster
      or slower than their respective counterparts. The faster-migrating RNAs were
      internally deleted, some of them possessing only the very terminal part of the 5'
      genomic end.

PMID- 9000098
TI  - Isolation and characterization of Tula virus, a distinct serotype in the genus
      Hantavirus, family Bunyaviridae.
AB  - A Vero E6 cell culture isolate of Tula virus (TUL), a hantavirus first detected
      in European common voles (Microtus arvalis and M. rossiaemeridionalis) by RT-PCR
      was obtained after initial passaging of TUL-infected vole lung samples in
      laboratory-colonized M. arvalis. TUL was defined as a classical serotype by a
      cross-focus-reduction neutralization test (FRNT) and was also shown to be
      distinct from other hantaviruses by haemagglutination inhibition assay. The
      sequences of S, M and partial L genome segments of the isolate were determined:
      the S segment was 99.9% identical to the original rodent-derived sequence.
      Serological evidence for a previous TUL infection was obtained from the serum of
      a blood donor living near a TUL focus in Moravia, Czech Republic, showing at
      least a 16-fold higher FRNT titre to TUL as compared to Puumala or other
      hantaviruses.

PMID- 9000099
TI  - Common localization of retention determinants in hepatitis B virus L protein from
      different strains.
AB  - Hepatitis B virus L protein is retained intracellularly, and trans-inhibits
      secretion of the related S and M proteins, as particulate HBsAg, at high L/S-M
      ratios. Comparison of equivalent A and D strain mutants suggested that the
      retention mechanism does not vary with genotype. Contrary to an earlier
      suggestion, the N-terminal extension specific for A-C strains was found to be
      inactive as a retention signal. Intact L was more completely retained than any
      mutated protein. Retained mutants had either a critical PreS stretch, or N
      terminal myristate. Also, mutants of the latter class did not completely inhibit
      particulate budding, and could, in minor amounts, reach the Golgi. We conclude
      that (i) the principal retention determinant can be traced to the same PreS
      segment in distinct strains and (ii) myristic acid does reinforce retention in
      wild-type L, while acting in part as an HBsAg membrane anchor in mutants lacking
      the internal determinant.

PMID- 9000100
TI  - Epstein-Barr virus binding to CD21, the virus receptor, activates resting B cells
      via an intracellular pathway that is linked to B cell infection.
AB  - Epstein-Barr virus (EBV) initiates infection of normal B lymphocytes by binding
      to CD21, a complement receptor. Since EBV, unlike most viruses, preferentially
      infects resting (non-activated) cells, the present studies were undertaken to
      evaluate the hypothesis that intracellular signalling pathway(s) triggered by EBV
      binding to CD21 activate the expression of certain cellular genes, as well as the
      initially expressed viral genes, and thus enable EBV to infect resting B cells.
      Experiments with nontransforming EBV, recombinant virus ligand and anti-CD2 1
      MAbs show that EBV binding to CD21 on resting B cells increases CD23 mRNA levels
      independently of viral gene expression. A panel of five protein kinase C (PKC)
      and tyrosine kinase (PTK) inhibitors, all with different modes of action,
      exhibited a distinctive pattern of effects on the EBV induced induction of CD23
      expression, ranging from nearly complete inhibition to no influence. The results
      suggest that distinct PKC isoforms and PTKs are involved in the signalling
      pathway(s) triggered by EBV binding to CD21. Significantly, the five inhibitors
      showed the same pattern of effects on the earliest stages of infection (EBNA-2
      transcription) and B cell transformation (mitogenesis and colony formation). The
      identical pattern of effects of these PKC and PTK inhibitors with diverse
      mechanisms of action on the EBV induced increase in both CD23 and EBNA-2 mRNA
      levels strongly suggests that their transcription is mediated by an intracellular
      signalling pathway which shares, at least in part, common members.

PMID- 9000101
TI  - Intracellular localization and expression of the human cytomegalovirus matrix
      phosphoprotein pp71 (ppUL82): evidence for its translocation into the nucleus.
AB  - A polyclonal antiserum, raised against a pp71 fusion protein, was prepared in
      order to investigate the biosynthesis and localization of the matrix protein pp71
      of human cytomegalovirus (HCMV), the UL82 gene product, during the HCMV
      infectious cycle in human fibroblasts. Transcription of the pp71-specific
      bicistronic 4.0 kb mRNA and pp71 biosynthesis exhibited a biphasic pattern during
      one round of the HCMV infectious cycle, with a first peak at 12 h and a second at
      72 h post-infection (p.i.). Cycloheximide treatment of infected human fibroblasts
      revealed that the presence of pp71 in total cell extracts prior to 3 h p.i. was
      due to the input virus inoculum. Transcription of the two specific pp71 mRNAs
      commenced 5-7 h p.i. as shown by Northern blot analysis of total cellular RNA.
      Western blot analysis of isolated nuclei and indirect immunofluorescence
      experiments indicated that pp71, like the major tegument protein pp65, is present
      in the nucleus shortly after infection as well as during the late phase of viral
      morphogenesis. Also, after transient transfection of UL82 into U37 3MG cells,
      pp71 was found to be present in the nucleus of the transfected cells. By
      immunogold labelling, pp71 was detected in the nucleoplasm in association with
      nucleocapsids in electron-dense nuclear skein structures at late stages of the
      infection cycle. These findings suggest functions of pp71 in viral maturation in
      addition to that as an early transactivator of viral gene transcription described
      recently.

PMID- 9000102
TI  - Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors.
AB  - The cellular sites and mechanisms of human cytomegalovirus (HCMV) latency are
      still poorly defined. Although evidence suggests that peripheral blood monocytes
      are one site of latency in the healthy carrier, it is unlikely that monocytes
      represent a site of primary HCMV infection. Consequently, we have analysed CD34+
      bone marrow progenitors, precursors of monocytes, to determine whether they are a
      site of HCMV carriage in normal virus carriers. For the first time, we
      demonstrate the presence of endogenous HCMV within bone marrow progenitors in the
      absence of HCMV lytic gene expression. These findings are consistent with
      previous evidence showing that the permissiveness of myeloid cells for HCMV is
      critically dependent on the differentiation state of the cell.

PMID- 9000103
TI  - Human herpesvirus 7 infection of CD4+(+) T cells does not require expression of
      the OKT4 epitope.
AB  - To evaluate the role of the OKT4 epitope in human herpesvirus 7 (HHV-7)
      infection, we studied the susceptibility to HHV-7 infection of CD4+ T cells
      isolated from two individuals with OKT4 epitope deficiency. HHV-7-infected OKT4
      Leu3a+ T cells exhibited the characteristic cytopathic effect, reactivity with
      HHV-7-seropositive serum by immunofluorescence and down-modulation of surface CD4
      in a manner similar to HHV-7-infected OKT4+Leu3a+ T cells. A semiquantitative PCR
      revealed that the amounts of HHV-7 replicated in OKT4+Leu3a+ T cells and OKT4
      Leu3a+ T cells were not significantly different. Although it has been reported
      that OKT4 monoclonal antibody efficiently inhibits HHV-7 infection, the present
      study demonstrated that the interaction of HHV-7 with CD4+ T cells does not
      require participation of the epitope defined by OKT4 monoclonal antibody.

PMID- 9000104
TI  - The dUTPases from herpes simplex virus type 1 and mouse mammary tumour virus are
      less specific than the Escherichia coli enzyme.
AB  - The enzyme dUTPase catalyses the hydrolysis of dUTP to dUMP and pyrophosphate,
      thereby suppressing incorporation of uracil into DNA and providing a pool of
      dUMP, the precursor of dTTP. Hydrolysis of other nucleotides similar in structure
      to dUTP would conceivably be physiologically detrimental and high specificity of
      the reaction seems to be necessary. In this work, we characterize the substrate
      specificity of the dUTPases from herpes simplex virus type 1 (HSV-1) and mouse
      mammary tumour virus (MMTV) in comparison to the Escherichia coli enzyme. We
      tested dCTP, dTTP, UTP and dUDP as substrates. Significantly higher reactivity
      was observed for the HSV-1 enzyme with dCTP and dTTP and for the MMTV enzyme with
      dTTP and UTP. The lower substrate specificity of the two virus enzymes compared
      with the bacterial enzyme is discussed in relation to the DNA precursor
      metabolism during virus replication.

PMID- 9000105
TI  - Similarity in genome organization between Molluscum contagiosum virus (MCV) and
      vaccinia virus (VV): identification of MCV homologues of the VV genes for protein
      kinase 2, structural protein VP8, RNA polymerase 35 kDa subunit and 3beta
      hydroxysteroid dehydrogenase.
AB  - Molluscum contagiosum virus (MCV) and vaccinia virus (VV) are serologically
      unrelated poxviruses with a disparate genome composition (MCV, 66% G+C; VV, 33%
      G+C). Molecular studies of MCV have been hindered by the inability to propagate
      the virus in cells cultured in vitro. We sequenced 7765 bp of MCV DNA cloned from
      four widely spaced regions throughout the MCV genome and identified a total of 11
      potential open reading frames (ORF), designated CX1-11. These include MCV
      homologues of the VV genes encoding protein kinase 2, structural protein VP8, RNA
      polymerase 35 kDa subunit and 3beta-hydroxysteroid dehydrogenase. The position
      and orientation of the MCV ORFs was collinear to the VV genome, with the
      exception of the region around ORF CX11 which is inverted in the MCV genome.

PMID- 9000107
TI  - Spodoptera exigua multicapsid nucleopolyhedrovirus deletion mutants generated in
      cell culture lack virulence in vivo.
AB  - The baculovirus Spodoptera exigua multicapsid nucleopolyhedrovirus (SeMNPV) has
      high potential for development as a bio-insecticide for control of the beet
      armyworm (S. exigua). It is highly infectious for S. exigua larvae and its host
      range is very narrow. A prerequisite for such application is the possibility of
      growing this virus in large quantities, e.g. in insect cell lines. It was
      observed, however, that polyhedra of SeMNPV plaque-purified in Se-UCR1 cells did
      not cause larval mortality or morbidity when fed to S. exigua larvae. As this
      suggested a genetic alteration in in vitro produced SeMNPV, comparative
      restriction analysis of in vitro and in vivo produced SeMNPV DNA was performed.
      The restriction patterns of viral DNA from several different plaques always
      differed from that of the wild-type in the same way, suggesting that a large,
      single deletion had occurred in the in vitro produced viral genome. In order to
      localize this deletion more precisely a detailed physical map of the wild-type
      SeMNPV genome was constructed, using the restriction endonucleases XbaI, BamHI,
      Bg/II, PstI, SstI, HindIII and SpeI. In addition, the entire SeMNPV genome was
      cloned into a library containing five overlapping cosmids and a plasmid library.
      About 80 restriction sites were located and the orientation of the map was set
      according to the location of the polyhedrin and p10 genes. The approximate size
      of the viral genome was 134 kbp. Based on this map it could be established that
      mutant SeMNPV, obtained by passage in cell culture, contained a single deletion
      of approximately 25 kbp between map units 12.9 and 32.3.

PMID- 9000106
TI  - Non-replicating recombinant vaccinia virus encoding murine B-7 molecules elicits
      effective costimulation of naive CD4+ splenocytes in vitro.
AB  - Using a series of new insertion/expression vectors, we constructed a set of
      recombinant vaccinia viruses (recVV) encoding the murine T cell costimulatory
      molecules mB7-1 or mB7-2, or both together in the same construct. On infection
      with replication incompetent and non-cytopathic recVV, several tumour cell lines
      expressed the respective molecules and bound to CTLA-4. The highest binding
      capacity was found when both mB7 molecules were co-expressed. Mouse B16.F10
      melanoma cells expressing mB7-1 or mB7-2 provided effective costimulation for
      proliferation of resting CD4+ T cells in the presence of concanavalin A and plate
      bound anti-T cell receptor antibodies, respectively. If mB7-1 and mB7-2 were
      delivered together on the same cell, the proliferative response of CD4+ T cells
      increased further. The costimulatory effect could be blocked with CTLA-4, the
      soluble ligand for B7 molecules. The possibility of engineering tumour cells
      using recVV holds implications for the future design of vaccination strategies.

PMID- 9000108
TI  - The genes encoding the P39 and CG30 proteins of Bombyx mori nuclear polyhedrosis
      virus.
AB  - We have cloned and analysed the transcriptional properties of two closely linked
      genes, p39 and cg30, of Bombyx mori nuclear polyhedrosis virus (BmNPV). These
      genes encode a structural polypeptide and a putative transcriptional regulator of
      the virus, respectively. The cg30 gene is transcribed prior to and after DNA
      replication from a site located within the ORF of the adjacent p39 gene. Its
      transcription product, a 1.3 kb mRNA, is polyadenylated at a site containing
      consensus eukaryotic polyadenylation signals and mapping 87 bp downstream of the
      translation termination codon for CG30. During the later stages of infection, two
      additional RNAs, 2.2 and 6.5 kb, are also transcribed through the cg30 gene. The
      2.2 kb RNA, representing the mRNA that encodes P39, is initiated from three
      relatively closely spaced sites located upstream of the P39 ORF. The 6.5 kb RNA
      is apparently transcribed from the promoter sequences of another gene located
      further upstream of the p39 gene. The 2.2 and 6.5 kb transcripts have two
      polyadenylation sites. The first site is the same as the one used to generate the
      cg30 gene-specific transcripts. The second is located 4 bp downstream of the CG30
      translation termination codon. Transient expression assays show that the p39 gene
      sequences immediately upstream of the CG30 ORF can direct expression of a
      reporter gene when the latter is co-transfected with the gene encoding the early
      baculovirus trans-activator IE1. Thus, these sequences behave as a delayed-early
      baculovirus gene promoter.

PMID- 9000109
TI  - Potyvirus transmission is not increased by pre-acquisition fasting of aphids
      reared on artificial diet.
AB  - Aphids (Myzus persicae), fasted after removal from healthy rearing plants,
      transmitted tobacco etch potyvirus (TEV) more efficiently than unfasted aphids
      whether virus acquisition was from infected leaves or through membranes. There
      was no difference in uptake of 125I-labelled TEV by fasted or unfasted aphids as
      measured by liquid scintillation counting. When aphids acquired 125I-labelled
      TEV, label was retained in the stylets (as determined by autoradiographic light
      microscopy) by 51 % of 272 fasted aphids, as against 7.8% of 258 unfasted aphids.
      There was a close correlation between virus transmission by aphids and virion
      retention in stylets. The effect of pre-acquisition fasting disappeared when
      aphids reared on an artificial diet were used in virus transmission tests. The
      transmission rates obtained with such aphids were similar to the rates with
      fasted aphids reared on healthy plants. Our results support the hypothesis that
      fasting eliminates plant component(s) which interfere with the retention of
      virions in the food canal of aphid stylets.

PMID- 9000110
TI  - Multiple viral determinants affect seed transmission of pea seedborne mosaic
      virus in Pisum sativum.
AB  - Two pea seedborne mosaic potyvirus (PSbMV) isolates, P-1 DPD1 (P-1), which is
      highly seed-transmitted, and P-4 NY (P-4), which is rarely seed-transmitted, and
      chimeras between P-1 and P-4 were analysed to map the viral genetic determinants
      of seed transmission. Infectivity of chimeric viruses was evaluated by
      inoculating Pisum sativum with RNA transcribed in vitro from recombinant full
      length cDNA clones. The chimeric viruses that were used demonstrated that a
      genomic segment encoding the 49 kDa protease and putative RNA polymerase was
      responsible for symptom induction. Attempts to determine transmission of the
      chimeric viruses in P. sativum cultivars known to transmit P1 at high frequencies
      showed that seed transmission is a quantitative character influenced by multiple
      viral determinants. Seed transmission frequency did not correlate with
      accumulation of virus in vegetative tissue. The 5' 2.5 kb of the 10 kb PSbMV
      genome had a major influence on the seed transmission frequency and was analysed
      further. This showed that, while the helper-component protease was a major
      determinant of seed transmission, the potyviral P1 -protease exerted no
      measurable influence.

PMID- 9000111
TI  - Genome segment 5 of rice ragged stunt virus encodes a virion protein.
AB  - The complete nucleotide sequence of the genome segment 5 (S5) of a Thai isolate
      of rice ragged stunt virus (RRSV) was determined. The 2682 nucleotide sequence
      contains a single long open reading frame capable of encoding a polypeptide with
      a molecular mass of approximately 91 kDa. Polypeptides encoded by various
      truncated cDNAs of S5 were expressed using the pGEX fusion protein vector and the
      highest level of fusion protein was obtained from a construct encoding a
      hydrophilic region of S5 protein. Antibodies raised against this fusion protein
      recognized a minor polypeptide, with a molecular mass of approximately 91 kDa,
      that was present in purified preparations of RRSV particles, infected insect
      vectors and infected rice plants. This indicates that RRSV S5 encodes a minor
      structural protein. Comparing the RRSV S5 sequence with sequences of other
      reoviruses did not reveal any significant sequence similarities.

PMID- 9000112
TI  - The effect of dry heat on the ME7 strain of mouse-passaged scrapie agent.
AB  - Partial survival of lyophilized scrapie agent has been reported previously
      following exposure to dry heat at 360 degrees C for 1 h, and led to speculation
      that scrapie-like agents might not be completely inactivated by incineration.
      However, it is known that dried infectivity is more difficult to inactivate by
      heat than that in hydrated samples. In this present study it was shown that the
      infectivity in macerates of mouse-brain infected with the ME7 strain of scrapie
      agent was not completely inactivated by exposure to dry heat at temperatures up
      to 180 degrees C for 1 h but the titre of surviving infectivity reduced
      progressively as the temperature was increased. No infectivity was recovered
      after a 1 h exposure at 200 degrees C. These data suggest that scrapie-like
      agents are unlikely to survive incineration.

PMID- 9000113
TI  - Alcohol induces formation of morphine precursors in the striatum of rats.
AB  - Dopamine-derived alkaloids, the tetrahydroisoquinolines (TIQs), are suspected to
      play a role in the pathogenesis of alcoholism. The present study describes the
      alcohol induced formation of the S-enantiomer of Tetrahydropapaveroline and
      Norcoclaurine in the rat brain. These compounds are of special interest since
      both were found as being intermediates in the biosynthesis of morphine in the
      opium poppy. The concentration of both TIQs were determined in different brain
      regions of Wistar rats after 6 and 18 months alcohol consumption ad libitum. Gas
      chromatography/mass spectrometry was used for the detection and quantification of
      the enantiomers. Tetrahydropapaveroline and norcoclaurine were detected only in
      the striatum of those rats which had consumed alcohol for 18 month, neither in
      other brain regions nor in any brain regions of the controls or the short term (6
      month) alcohol treated rats. These findings and the fact that those
      tetrahydroisoquinolines were only detected in the striatum of the alcohol fed
      rats and were present only as the S-enantiomers suggest that an alcohol induced
      biosynthetic pathway exists in the mammalian brain.

PMID- 9000114
TI  - Characterization of a novel iodinated ligand, IPMPP, for human dopamine D4
      receptors expressed in CHO cells.
AB  - A novel radioiodinated ligand with a high specific activity (2,200 Ci/mmol), 3-[4
      (4-iodophenyl)piperazin-1-yl]methyl-1H-pyrrolo(2,3-b)pyridine ([125I]IPMPP), was
      successfully prepared. Binding characteristics of [125I]IPMPP were evaluated
      using human dopamine D4 (D4.2 variant) receptors expressed in Chinese hamster
      ovary (CHO) cells. Saturation analysis revealed high-affinity binding sites for
      [125I]IPMPP (Kd = 0.39 +/- 0.18 nM). The number of D4 receptors labeled with
      [125I]IPMPP at room temperature was four times higher than that labeled with
      [125I]S(-)5-OH-PIPAT, a radioiodinated agonist ligand (572 fmol/mg protein vs.
      125 fmol/mg protein). A significant decrease in the number of binding sites was
      observed with [125I]S(-)5-OH-PIPAT when assays were carried out at a higher
      temperature (37 degrees C vs. 25 degrees C). In contrast to [125I]S(-)5-OH-PIPAT,
      [125I]IPMPP labeled more D4 sites at 37 degrees C. Neither magnesium ion nor
      guanylimidodiphosphate (Gpp(NH)p) affected [125I]IPMPP binding. These data
      support the conclusion that [125I]IPMPP is an antagonist ligand. The potency of
      various compounds, including clozapine, to inhibit [125I]IPMPP binding is
      consistent with the rank order measured with other radioligands for D4 receptors.
      In addition, measuring D4 receptor stimulation of [35S]GTPgammaS binding further
      demonstrated the antagonist property of IPMPP.

PMID- 9000115
TI  - Pharmacokinetics of a new nitroderivative of acetylsalicylic acid after a single
      dose in rats.
AB  - The pharmacokinetics of a new ASA-nitroderivative compound, NCX 4016 (ASA-NO2),
      was evaluated using an HPLC method. After single equimolar doses of ASA (35 mg
      kg(-1)) or ASA-NO2 (65 mg kg(-1)), no detectable levels of these compounds have
      been observed in rat plasma samples. SA peak levels were obtained at 3 h and 6 h
      after ASA and ASA-NO2 administration respectively. The elimination rate constants
      of SA were similar after ASA and ASA-NO2, suggesting a similar elimination phase
      of this metabolite in rats. From these data it is evident that ASA-NO2 is slowly
      metabolized in ASA, which is rapidly converted to SA.

PMID- 9000116
TI  - A new type of Ca-channel modulation by a novel class of 1,4-dihydropyridines.
AB  - Both Ca-antagonistic as well as Ca-agonistic 1,4-dihydropyridines (DHPs) have
      become extremely important tools to investigate the role of Ca-channels under
      various physiological and pathophysiological conditions. While Ca-antagonists
      stabilize the inactivated state of the Ca-channel without influencing the voltage
      dependent open and closed times, Ca-agonists prolong the mean open time of the
      channel. We here report for the first time the effects of a novel DHP, BAY Y
      5959, which modulates Ca-channel gating in a unique manner: It increases both the
      mean open time and the mean closed time of the Ca-channel by binding to the DHP
      receptor. This results in a reduced rate of Ca-current activation, an increased
      peak current, and a strongly prolonged tail current decay. All these effects are
      strongly voltage dependent. Therefore it depends on resting membrane potential
      and shape of the action potential whether and how the Ca-influx into the cell is
      influenced. This novel mode of action of BAY Y 5959 results in an interesting
      pharmacological profile: It has a strong positive inotropic effect in the heart
      without influencing vessel tone. Therefore the term Ca-promoter is suggested; it
      could become a new approach for the drug treatment of congestive heart failure.

PMID- 9000117
TI  - Blockade of the inward rectifier potassium currents by zinc and nickel ions in
      voltage-clamped toad muscles.
AB  - The inward rectifier is one of the voltage-sensitive K+ channels present in
      several tissues: Its conductance increases under hyperpolarization and decreases
      with depolarization. In this work we studied the effects of Zn2+ and Ni2+ (5-30
      mM) on the macroscopic K+ current through the inward rectifier system. The
      experiments were performed in the short muscle fibers of the lumbricalis muscle
      of toads with a two-microelectrode voltage clamp technique. The fibers were
      equilibrated in a control solution containing 68 mM K2SO4 and then exposed to
      Zn2+ or Ni2+. We found that both cations reduced in a reversible manner the
      current carried by K+ ions, and this reduction was prevented by decreasing the
      external pH of the solution (pH 5). The blockade of current was slightly
      dependent on the membrane potential and time independent. Two mechanisms may be
      involved in the blocking action of these cations: Zn2+ and Ni2+ may either be
      blocking the pore of the channels or acting at a regulatory binding site on the
      extracellular surface in an unspecified manner.

PMID- 9000118
TI  - Bufalin inhibits endothelial cell proliferation and angiogenesis in vitro.
AB  - We have investigated the effects of bufalin, one of the prominent components in
      Chinese toad venom, on proliferation of bovine aortic endothelial (BAE) cells and
      tube formation in three-dimensional type I collagen matrix. In the present study,
      bufalin potently inhibited the formation of capillary-like tubular networks in a
      dose-dependent manner. Bufalin also inhibited the proliferation of BAE cells at
      the same concentration (5 nM) that the tube formation was inhibited. As a potent
      inhibitor of endothelial cell proliferation, bufalin specifically prevented the
      entry of BAE cells into the G0/G1 phase of a cell cycle. These findings suggest
      that in vitro angioinhibitory action of bufalin may be induced by the
      proliferation inhibition of endothelial cells through the arrest at the G2/M
      phase of a cell cycle.

PMID- 9000119
TI  - Effect of (-)-epigallocatechin gallate on leukemic blast cells from patients with
      acute myeloblastic leukemia.
AB  - Information on the anti-carcinogenic effect of EGCG, the main constituent of the
      polyphenols present in Japanese green tea leaves, has recently been accumulating.
      In this report, we evaluate the effect of EGCG on leukemic blast cells from AML
      patients. The results showed that EGCG inhibited the proliferation of AML cells
      in all cases examined. Since AML cells might proliferate by autocrine or
      paracrine growth mechanisms, we also examined the effect of EGCG on the
      production of GM-CSF from AML cells. Although EGCG did not directly inhibit the
      production of GM-CSF, it did inhibit the effect of TNF-alpha or TPA, both of
      which stimulated AML cells to produce GM-CSF. On the other hand, the modulation
      of receptors for growth factors might play a role in the proliferation or
      carcinogenesis of AML cells. We also found that EGCG inhibited the modulation of
      c-kit, a receptor for stem cell factor, on leukemic cells. These findings
      suggested that EGCG might be available as a new therapeutic tool for AML
      patients.

PMID- 9000120
TI  - Effects of ischemia-reperfusion on individual cytochrome P450 isoforms in the rat
      kidney.
AB  - Ischemia-reperfusion of organs such as the kidney produces reactive oxygen and
      free radical species in tissues and leads to injury of intracellular molecules
      critical to cell homeostasis. Ischemia-reperfusion affects the NADPH-dependent
      monooxygenase system including P450 system, which is also a source of reactive
      oxygen species. In this study, the effects of ischemia-reperfusion on
      monooxygenase activity and levels of individual P450 isoforms including CYP2C23,
      4A2, and 4A8 in the rat kidney were investigated. Ischemia of the rat kidney for
      30 min had little effect on lauric acid hydroxylation activity and levels of P450
      isoforms but ischemia for 60 min significantly decreased lauric acid omega- and
      (omega-1)-hydroxylation activities and also decreased the levels of CYP2C23, 4A2,
      and 4A8. Reperfusion for 60 min after 30-min ischemia decreased the levels of
      CYP2C23 and 4A2 in the rat kidney although 30-min ischemia did not. Reperfusion
      for 240 min after 30-min or 60-min ischemia recovered the decreased levels of
      lauric acid hydroxylation activity and the levels of CYP2C23 and 4A2. Changes in
      the levels of monooxygenase activity and the levels of P450 isoforms in kidneys
      by ischemia-reperfusion are faster than those in the liver; it takes several
      hours for ischemia-reperfusion to affect the levels of monooxygenase activity and
      the levels of P450 in the rat liver. Our findings suggest that damage of P450
      isoforms in the kidney by ischemia-reperfusion occurs by a mechanism different
      from that in the liver and that active oxygen or free radical species directly
      attack proteins.

PMID- 9000121
TI  - Evolution of dopamine receptors in the rat after neonatal hypoxia-ischemia:
      autoradiographic studies.
AB  - The aim of this work was to follow the evolution of striatal dopamine D1 and D2
      receptors after hypoxic-ischemic (H/I) insult in immature rats. SPET imaging of
      these receptors could be used as an index to assess brain dysfunctions after
      perinatal H/I without change in cerebral blood flow or neuronal loss. We
      submitted 1-week-old rat pups to unilateral ligation of the left carotid artery
      plus 2h exposure to 8% O2. After recovery periods of 1, 2 or 9 weeks, ex vivo and
      in vitro autoradiographic studies of dopamine receptors were performed on normal
      appearing brains using specific ligands usable in human SPET imaging. Striatal
      dopamine D2 receptors tended to decrease bilaterally after one week's recovery.
      The decrease then reached 40% at 3 weeks of age and at 10 weeks of age the level
      of receptors had returned to normal values. By contrast, no change in dopamine D1
      receptors was seen, whatever the age studied. In conclusion, changes in dopamine
      D2 receptors could be a valuable index for SPET imaging to evaluate H/I brain
      damage in the absence of anatomical lesions.

PMID- 9000122
TI  - Melatonin is protective against MPTP-induced striatal and hippocampal lesions.
AB  - The in vivo effect of melatonin on MPTP-induced neurotoxicity in mouse brain was
      studied. Melatonin (10 mg/kg) or saline was administered intraperitoneally (i.p.)
      to mice 30 min prior to a s.c. injection of MPTP (20 mg/kg). After MPTP
      treatment, the animals received melatonin or saline injections every hour for
      three hours. Mice were killed 4 hours after the MPTP injection. Regionally
      specific increases in lipid peroxidation were observed in corpus striatum and
      hippocampus (71% and 58%, respectively), but not in cerebral cortex, cerebellum
      or midbrain. Treatment with melatonin completely reversed the rises in lipid
      peroxidation products. MPTP-treated mice showed a significant decrease in the
      striatal tyrosine hydroxylase immunoreactive nerve terminals, an effect that was
      also prevented by melatonin. These data show that melatonin is neuroprotective in
      this MPTP model of Parkinson's disease and suggest that melatonin, an endogenous
      antioxidant and nontoxic compound, may have potential beneficial effects for this
      neurodegenerative disorder.

PMID- 9000123
TI  - A study on rat platelet responsiveness following intravenous endotoxin
      administration.
AB  - The aim of the present study was to evaluate platelet responsiveness in rats
      following E.coli endotoxin administration. Injection of E.coli to rats caused a
      reduction in ADP-induced pulmonary 111In labelled platelet accumulation four
      hours later. Similarly, when platelet aggregation was evaluated on PRP obtained
      from rats four hours after endotoxin administration, we found that platelet
      response to both ADP and collagen was significantly reduced. When platelets
      obtained from endotoxemic rats were suspended in normal plasma, the aggregating
      response to ADP and collagen was not different from that obtained with control
      platelets. Similarly, platelets from control rats suspended in plasma from
      endotoxemic rats showed hyporesponsiveness to ADP and collagen. There was no
      difference in the aggregatory response to collagen or to thrombin of washed
      platelet suspension (WPS) obtained from endotoxemic and normal rats. In
      conclusion, by using an in vivo minimally invasive technique and an ex vivo
      platelet aggregation test we demonstrate that during endotoxemia platelet are
      functionally unaltered and the platelet hyporesponsiveness is only observed in
      presence of plasma.

PMID- 9000124
TI  - G1 phase-specific suppression of the Cdk2 activity by ginsenoside Rh2 in cultured
      murine cells.
AB  - Ginsenoside Rh2, a plant glycoside with a dammarane skeleton resembling a steroid
      skeleton as an aglycone, has anticancer potentials in vitro or in vivo. To
      elucidate the molecular mechanisms of the effects of Rh2, we have examined the
      Cyclin-dependent kinase-2 (Cdk2) activity in G1 arrested B16 melanoma cells and
      in S phase-arrested Meth-A sarcoma cells, that have been treated with Rh2. The
      kinase activity was suppressed in B16 cells but not in Meth-A cells. In addition,
      Rh2 was found to induce G1 arrest and concomitantly suppress the Cdk2 activity in
      carcinogen-susceptible BALB/c 3T3 A31-1-1 and A31-1-13 cell lines. Thus, Rh2 has
      a G1 phase-specific suppressive effect on the Cdk2 activity, supporting further
      evaluation of Rh2 and its related compounds in cancer chemoprevention studies.

PMID- 9000125
TI  - Keratinocyte growth factor induces mammary and prostatic hyperplasia and mammary
      adenocarcinoma in transgenic mice.
AB  - The kinetics of solitary mammary tumor formation in transgenic mice bearing the
      MMTV-int-2 (fgf3) fusion gene suggest that several genetic events are required
      for tumorigenesis. In an effort to identify elements that could contribute to
      this oncogenic process, we used differential display PCR to identify gene
      products that are strongly and specifically induced in int-2 mammary tumors.
      Using this approach we identified a member of the FGF family, kgf (fgf7), as a
      gene that is strongly upregulated in an int-2-containing mammary tumor. Since int
      2 and kgf strongly bind the same receptor, the IIIb isoform of FGFR2, it is
      possible that their joint expression, one as a transgene, the other as an
      activated gene, might reinforce the same mitogenic pathway. To test this
      possibility, we created transgenic mice that carry kgf as a transgene gene under
      the control of the MMTV promoter/enhancer. Female mice carrying this transgene
      develop a very dramatic mammary epithelial hyperplasia and go on to develop
      solitary, metastatic adenocarcinomas of the mammary gland. Consistent with a
      common signalling pathway, the MMTV-kgf-induced hyperplasia has the morphologic
      characteristics of that seen in the MMTV-int-2 mice. Male mice also develop
      hyperplasia of the male genital tract, including the seminal vesicle, the vas
      deferens and the prostate. Thus KGF can act as a potent proliferative inducer in
      mammary and specific urogenital tissue and can contribute to the development of
      adenocarcinoma of the mammary gland in a manner strongly reminiscent of receptor
      related ligand, int-2.

PMID- 9000126
TI  - PKC epsilon functions as an oncogene by enhancing activation of the Raf kinase.
AB  - Previous studies have indicated that PKCepsilon behaves as an oncogene when
      overproduced in rodent fibroblasts (Cacace et al., 1993; Mishak et al., 1993). In
      the present study, Western blot analysis revealed that the hyperphosphorylated
      form of Raf kinase was present at a high level in PKCepsilon overproducing R6 rat
      fibroblasts but not in R6 fibroblasts overproducing PKCalpha or beta1. Extracts
      from the PKCepsilon overproducing cells also exhibited a marked increase in Raf-1
      kinase and MAP-kinase activity. To investigate the significance of these
      findings, dominant negative mutants of ras (N17) or raf (301-1) were stably
      expressed in early passage control and PKCepsilon-transformed R6 fibroblasts, by
      transduction using retrovirus-derived constructs. Dominant negative raf
      expressing clones exhibited a flat morphology, a decreased saturation density,
      and decreased growth in soft agar. In addition, these reverted clones exhibited
      decreased Raf kinase activity. In contrast, dominant negative ras expressing
      clones remained highly transformed. In addition, PKCepsilon was detected in Raf-1
      immunoprecipitates indicating that PKCepsilon forms a complex with Raf-1 in vivo.
      Taken together, these results suggest that PKCepsilon functions as an oncogene in
      R6 cells by enhancing activation of the Raf-1 kinase.

PMID- 9000127
TI  - Differential effects of phosphorylation of rat p53 on transactivation of
      promoters derived from different p53 responsive genes.
AB  - The tumor suppressor protein p53 is phosphorylated at multiple sites in the amino
      terminal transactivation domain and at several sites in the carboxy-terminal
      region. Phosphorylation appears to modulate its DNA binding activity. Here we
      demonstrate that phosphorylation of p53 also modulates its transcriptional
      activity. Okadaic acid treatment of cells resulted in enhanced phosphorylation of
      p53 and concomitantly in enhanced transactivation of an mdm2 promoter-linked
      luciferase reporter gene. This effect was cell type specific, however, since
      transactivation was enhanced in rat and mouse fibroblasts but reduced in the
      human Saos-2 cell line. Moreover, the effect was dependent on the promoter. In
      rat cells transcription from the mdm2, waf1 (cip1) and bax gene promoters, and
      the artificial PG13 promoter was enhanced by okadaic acid treatment whereas that
      from the cyclin G promoter was reduced. When various phosphorylation site mutants
      of p53 were tested for transactivation of these promoters, they behaved
      differently. Amino-terminal mutants exhibited reduced transcriptional activities
      on mdm2, waf1 and cyclin G promoters but enhanced activities with bax and PG13
      promoters. On the other hand, a mutant at the cdk phosphorylation site, A313,
      showed reduced activity with mdm2 and waf1 promoters but enhanced activity with
      the cyclin G promoter, and finally, mutant A390 exhibited enhanced activity on
      waf1 and bax promoters, but reduced activity on the cyclin G promoter. These
      results suggest that phosphorylation of p53 may have different effects on its
      transcriptional activity, depending on the cellular environment and the
      particular response element. Moreover, both, amino- and carboxy-terminal
      phosphorylation sites seem to be involved in modulating the DNA-binding and the
      transactivation activities.

PMID- 9000128
TI  - Epstein-Barr virus nuclear antigen (EBNA)3C is an immortalizing oncoprotein with
      similar properties to adenovirus E1A and papillomavirus E7.
AB  - Epstein-Barr virus (EBV) requires six genes to efficiently immortalize human B
      cells. We have shown that one of these, EBNA3C, can cooperate with activated (Ha
      )ras in co-transfection assays to immortalize and transform rat embryo
      fibroblasts (REFs). EBNA3C also augmented transformation by (Ha-)ras and a mutant
      p53 to a similar extent as human papilloma virus E7. As with E7 this effect was
      not inhibited by cotransfection with the cyclin-dependent kinase inhibitor
      (CDKI), a p16INK4A, which can normally activate the retinoblastoma protein (pRb)
      and induce growth arrest. Also like E7/ras and E1A/ras transformed cells the
      EBNA3C/ras transformants are very susceptible to apoptotic cell death. In vitro
      EBNA3C binds to pRb in a manner which is dependent on the integrity of the pocket
      domain; this suggests that EBNA3C, even though it lacks the LXCXE pRb binding
      motif found in E7 and E1A, may interact with pRb in vivo. We conclude that EBNA3C
      functions as an oncoprotein which directs cell cycle progression through the G1
      phase restriction point when conditions might signal arrest. For the first time
      this demonstrates that EBV encodes a protein, functionally but not necessarily
      mechanistically, similar to the pRb-neutralizing nuclear antigens encoded by the
      'small' DNA tumor viruses.

PMID- 9000129
TI  - Functional characterization of COM, a DNA region required for cooperation between
      AP-1 sites in urokinase gene transcription.
AB  - The inducible uPA enhancer contains two phorbol ester responsive elements: the
      combined PEA3/AP-1A and a downstream AP-1B site. The integrity of all three sites
      is essential for enhancer activity. The interposed 74 bp long DNA region (COM,
      Cooperation Mediator) is in turn required for the synergistic action of the
      PEA3/AP-1 and AP-1 sites. Here we present a characterization of the COM sequence:
      our results show that COM and COM-binding proteins (UEF, Urokinase Enhancer
      Factors) may play a structural role in the induction of the uPA enhancer by
      phorbol-myristate-acetate (TPA). (1) COM has a bipartite structure (uCOM and
      dCOM) and each half contributes by about 50% to the COM-mediated TPA induction.
      (2) COM function is strictly dependent on its position, but not on its
      orientation and neither the entire COM nor individual UEF-binding sites can
      directly transactivate a test promoter. (3) The requirement for COM in TPA
      induction is partly eliminated by the deletion of COM sequence. However, also in
      the COM-deleted enhancer, integrity of the PEA3/AP-1A and AP-1B sites is
      essential for enhancer function. We conclude that COM and COM-binding proteins
      provide a structural surface which facilitates the cooperation between the
      transactivator proteins bound at the PEA3/AP-1A and AP-1B sites. Sequences
      homologous to uCOM are found in the promoters of other inducible genes, coding
      for proteases, cytokines and chemokines: for example, in the promoter of the MIP
      1alpha/LD78 chemokine gene, a 15/18 nucleotides identity is found in a region
      mediating positive and negative functions in TPA induction. Thus, COM-like
      elements represent a general enhancer function which, although lacking an
      intrinsic transactivating capacity, modulates the synergism between transcription
      factors bound to distant sites.

PMID- 9000130
TI  - Molecular cloning of the epidermal growth factor-stimulated protein kinase p56
      KKIAMRE.
AB  - A 56 kDa protein kinase was molecularly cloned from human fetal brain. This
      protein kinase (p56 KKIAMRE) shares homology with p42 KKIALRE (Meyerson et al.,
      1992) and is related to the proline-directed protein kinase group of signal
      transducing enzymes. The p56 KKIAMRE and p42 KKIALRE protein kinases exhibit
      mutually exclusive expression in reproductive tissues; p56 KKIAMRE in testis and
      p42 KKIALRE in ovary. p56 KKIAMRE and p42 KKIALRE may therefore contribute to
      signal transduction within these highly differentiated tissues. p56 KKIAMRE and
      p42 KKIALRE are activated by treatment of cells with epidermal growth factor
      (EGF). Although p56 KKIAMRE and p42 KKIALRE contain the MAP kinase dual
      phosphorylation motif Thr-Xaa-Tyr (Thr-Asp-Tyr), phosphorylation on Thr and Tyr
      within this motif is not required for EGF-stimulated protein kinase activity.

PMID- 9000131
TI  - The p53 response to ionising radiation in adult and developing murine tissues.
AB  - The induction of the p53 response to ionising radiation has been studied during
      murine development and in the adult animal. The response has been assessed by
      precise quantitative assay of p53 protein levels in tissues and by
      immunohistochemistry. Newly developed transgenic mice in which a lacZ transgene
      is driven by a p53 response element have also been used to directly assess the
      transcriptional activity of the induced protein. There is striking developmental
      control of the p53 response so that in early development all tissues accumulate
      high levels of p53 following radiation and indeed p53 is present at elevated
      levels in some unirradiated tissues. Later in development clear heterogeneity of
      the p53 response becomes apparent, both in terms of the responses of individual
      tissues and of cell populations, within those tissues. The study of lacZ
      transgene expression and the occurrence of apoptosis in different tissues that
      accumulate p53 protein point to a further level of control regulating the nature
      and degree of the downstream response to elevated levels of p53 in cells. These
      findings have important implications for the susceptibility of different tissue
      types to carcinogenic and other insults. The early expression of the p53 response
      is consistent with novel models of p53 function that suggest it may have evolved
      principally as a defense against teratogenic insult that permits plasticity of
      development.

PMID- 9000132
TI  - The BCR-ABL tyrosine kinase inhibits apoptosis by activating a Ras-dependent
      signaling pathway.
AB  - BCR-ABL is a deregulated tyrosine kinase that is expressed in Philadelphia
      chromosome (Ph1) positive human leukemias. When expressed in hematopoietic cells,
      BCR-ABL causes cytokine independent proliferation, induces tumorigenic growth and
      prevents apoptosis in response to cytokine deprivation or DNA damage. One
      mechanism by which BCR-ABL signals in cells is by activating the small guanine
      nucleotide binding protein Ras. BCR-ABL-transformed cells have constitutively
      high levels of active, GTP-bound Ras. Here we use 32D cells that inducibly
      express a dominant negative Ras protein to define the Ras requirements in BCR-ABL
      transformed cells. Dominant negative Ras inhibits BCR-ABL-mediated Ras
      activation, and induces cell death by an apoptotic mechanism. Therefore, BCR-ABL
      inhibits apoptosis through activation of a Ras-dependent signaling pathway.

PMID- 9000133
TI  - Critical role for the tyrosine kinase Syk in signalling through the high affinity
      IgE receptor of mast cells.
AB  - Activation of the high affinity IgE receptor (Fc epsilon RI) of mast cells, a
      member of the antigen receptor family, leads to the release of allergic
      mediators, a critical event in the onset of immediate hypersensitivity.
      Stimulation of Fc epsilon RI results in the rapid association and activation of
      the Syk tyrosine kinase. Using Syk-deficient mast cells we show that they fail to
      degranulate, synthesize leukotrienes and secrete cytokines when stimulated
      through Fc epsilon RI, conclusively demonstrating an essential role for Syk in Fc
      epsilon RI signalling. Furthermore, our data strongly supports a model of Fc
      epsilon RI engagement leading to the sequential activation of the tyrosine
      kinases Lyn and then Syk. A similar mechanism is likely to apply to signal
      transduction through all members of the antigen receptor family.

PMID- 9000134
TI  - Requirement for Y706 of the murine (or Y708 of the human) CSF-1 receptor for
      STAT1 activation in response to CSF-1.
AB  - Using FDC-P1 derived cell lines which ectopically express either the wild type or
      mutant forms of the murine CSF-1 receptor in which individual tyrosine residues
      have been replaced with phenylalanine, we analysed the requirement for tyrosine
      residues of the receptor for the activation of STAT proteins in response to CSF
      1. We found Y706 to be required for efficient activation of STAT1. The activation
      of STAT3 was not affected by the mutation of Y706 to phenylalanine. The addition
      of phosphopeptides spanning Y708 of the human CSF-1 receptor (identical with the
      sequence surrounding Y706 of the murine receptor) to electrophoretic mobility
      shift assays led to competition of the formation of STAT1 containing complexes,
      SIF-B and SIF-C with the DNA probe. These phosphopeptides did, however, not
      affect the formation of the STAT3 containing complex, SIF-A, with the probe.
      Replacement of Y807 with phenylalanine led to a complete block of activation of
      all STAT proteins in response to CSF-1, however, this phosphotyrosine does not
      appear to represent a STAT binding site of the receptor as a phosphopeptide
      spanning Y809 of the human CSF-1 receptor could not compete any STAT/DNA complex
      formation in electrophoretic mobility shift assays.

PMID- 9000135
TI  - Evidence of a novel redox-linked activation mechanism for the Src kinase which is
      independent of tyrosine 527-mediated regulation.
AB  - The kinase activity of p60c-src has been shown to be basically regulated through
      phosphorylation and dephosphorylation of Y527. We found that catalytic activity
      of the immunoprecipitated c-Src kinase from NIH3T3 cells was elevated several
      folds by exposure to 0.5-50 microM of sulfhydryl-reactive Hg2+. Vmax of the
      kinase was increased whereas Km was decreased. N-acetylcysteine neutralized this
      Hg2+ effect, suggesting a critical role of the Hg2+-mediated sulfhydryl
      modification of the kinase in the mechanism. Addition of protein tyrosine
      phosphatase inhibitor Na3VO4 into the reaction mixture did not inhibit the Hg2+
      mediated activation. Further study revealed that Hg2+ was capable of activating
      the v-Src kinase lacking Y527 and the c-Src kinase from mutant cells defective of
      the Y527-phosphorylating Csk kinase. Cyanogen bromide cleavage maps of
      radiolabeled Src proteins showed that Hg2+ selectively promoted the
      autophosphorylation at Y416 and that the previously in vivo radiolabeled
      phosphorous on Y527 was not deleted during the promotion of Y416
      autophosphorylation by Hg2+. Phosphoamino acid analysis demonstrated selective
      promotion of phosphorylation at tyrosine but not at serine/threonine. Not like
      bivalent Hg2+, monovalent p-chloromercuribenzenesulfonic acid was incapable of
      activating c-Src kinase. These results suggest a novel Y416 phosphorylation
      linked activation pathway for Src kinases which is initially triggered
      independent of Y527-mediated or serine/threonine phosphorylation-linked
      regulation, possibly through sulfhydryl-based protein structural modification for
      functional alteration.

PMID- 9000136
TI  - Identification of Bcd, a novel proto-oncogene expressed in B-cells.
AB  - A novel B-cell derived (Bcd) oncogene has been isolated from the peripheral blood
      lymphocytes of one B-cell chronic lymphocytic leukemia (B-CLL) patient using DNA
      transfer and a mouse tumorigenicity assay. The Bcd proto-oncogene was activated
      by a truncation in the 5' UTR. It predicts for two open reading frames (ORFs).
      ORF1 consists of 240 bp that would encode 80 amino acids, while the major ORF2
      consists of 648 bp capable of coding for 216 amino acids. Predicted peptide
      sequence of ORF2 contained a zinc finger domain which showed significant homology
      to GC box binding proteins BTEB2 and SP1. Transfection of an expression vector
      containing ORF2 but not full length cDNA was able to transform NIH3T3 cells and
      induce tumors in nude mice. Bcd mRNA transcripts of < or = 2.6 kb were
      selectively expressed in PBL and testis of healthy individuals. Within the PBL,
      Bcd gene expression was restricted to CD19+ B-cells and absent from CD14+
      monocytes and T-cells. Bcd transcripts were detected in all normal PBL samples
      tested but not in several malignant human B-cell lines and not in 50% of B-cells
      from B-CLL patients. However, stimulation of B-cells from B-CLL patients under
      conditions which induced differentiation into plasma cells was associated with
      induction of Bcd gene expression. The Bcd gene may therefore play an important
      role in B-cell growth and development.

PMID- 9000137
TI  - Expression of wild-type p53 stimulates an increase in both Bax and Bcl-xL protein
      content in HT29 cells.
AB  - It has been shown previously that wild-type p53 activity can simultaneously up
      regulate Bax, a protein which predisposes cells to programmed cell death (PCD),
      and down-regulate Bcl-2, a protein which antagonizes PCD. These findings have
      been interpreted to suggest that correction of the mutant p53 status of some
      tumor cells may be a means of increasing their sensitivity to chemotherapeutic
      agents, by increasing their likelihood of undergoing PCD. We show here that when
      wild-type p53 activity is expressed in HT29 human colon cancer cells by use of a
      temperature sensitive p53 mutant, Bax levels rise, but so do levels of Bcl-xL
      protein. These observations indicate that Bcl-2 and Bcl-xL are regulated
      differently in response to wild-type p53 activity and that, while correction of
      mutant p53 phenotype may effectively kill cells having Bcl-2 as their major
      defense against PCD, this is not necessarily the case in cells using Bcl-xL as
      their primary defense.

PMID- 9000138
TI  - JunD phosphorylation, and expression of AP-1 DNA binding activity modulated by
      serum growth factors in quiescent murine 3T3T cells.
AB  - JunD has been implicated as a negative regulator of cell proliferation. If and
      how JunD is regulated by growth factors however has not been well investigated.
      We now report that in quiescent murine 3T3T cells, JunD is present in a
      hypophosphorylated form, but that when quiescent cells are stimulated to
      proliferate with serum, JunD undergoes a transient increase in its
      phosphorylation that occurs within 10 min and persists for up to 4 h. The
      increase in JunD phosphorylation correlates with the induction of cell
      proliferation since only those growth factors that promote cell proliferation can
      induce JunD phosphorylation. Treatment of quiescent 3T3T cells with serum also
      induces significant decreases in JunD/AP-1 DNA binding activity within 2 h and in
      JunD expression after 8-48h. However, both hypophosphorylated and
      hyperphosphorylated forms of JunD can bind AP-1 DNA. These results suggest that
      serum growth factors can modulate JunD characteristics in a variety of apparently
      independent ways to overcome its negative regulatory effect in controlling cell
      proliferation. These include induction of a transient increase in JunD
      phosphorylation, repression of JunD AP-1 DNA binding activity and downregulation
      of JunD expression.

PMID- 9000139
TI  - EAT-2 is a novel SH2 domain containing protein that is up regulated by Ewing's
      sarcoma EWS/FLI1 fusion gene.
AB  - The EWS/FLI1 fusion protein is created by the translocation between chromosomes
      11 and 22 that appears in most Ewing's sarcomas. This chimeric protein has been
      demonstrated to be an aberrant transcription factor. Genes up regulated by
      EWS/FLI1 but not by full-length FLI1 were identified by representational
      difference analysis (RDA). We have characterized a novel gene, EWS/FLI1 activated
      transcript 2 (EAT-2) that was cloned from a murine cDNA library using a
      differentially expressed RDA fragment. EAT-2 expression is seen within 4-8 h of
      EWS/FLI1 induction. Its expression correlates with transformation of NIH3T3 cells
      by chimeric proteins related to EWS/FLI1 but not by unrelated genes. EAT-2 is
      expressed in normal murine tissues and contains a unique but biochemically
      functional SH2 domain. An homologous sequence in the human genome has been
      identified and mapped to chromosome 1q22. Human EAT-2 transcripts were identified
      by reverse transcriptase-polymerase chain reaction (RT-PCR) in Ewing's sarcoma
      cell tumour cell lines. EAT-2's unique structure and correlation with
      transformation make it a candidate for playing a role in the transformation of
      NIH3T3 cells and the oncogenesis of Ewing's sarcoma.

PMID- 9000141
TI  - Genomic structure and developmental expression of the mouse cell cycle regulatory
      transcription factor DP1.
AB  - The E2F/DP family of transcription factors play an important role in the control
      of cell cycle progression. By direct regulatory interactions with the
      retinoblastoma family of proteins, they integrate extracellular growth promoting
      signals impinging on the cyclin and cyclin dependent kinase complex during the G1
      phase, with cell cycle progression. This is accomplished by direct
      transcriptional activation of genes required for nucleotide biosynthesis and DNA
      replication in the S phase. In addition, these transcription factors also play a
      role in the control of genes involved in regulating G1 and S phase progression
      including, autoregulatory control, as in the case of E2F1 itself. In this report,
      we describe the characterisation of the genomic locus encoding DP1, a member of
      this family. The DP1 gene has a TATA-less promoter and transcription initiates at
      multiple sites. Using transient transfection assays we have delineated sequences
      in the upstream region which have promoter or enhancer activity. The DP1 gene was
      localised to mouse chromosome 8 by metaphase chromosome analysis. We describe a
      dynamic pattern of DP1 expression using in situ hybridisation on cryostat
      sections of mouse embryos at various stages of development and a variable level
      of expression by Northern blot analysis of RNA from various adult tissues.

PMID- 9000140
TI  - Induction of a complex between rasGAP and a novel 110 kD protein is required for
      immortalization of primary epithelial cells by the E1A 12S oncoprotein of
      adenovirus.
AB  - Although established cell lines can be transformed with oncogenic ras, primary
      epithelial cells cannot, but require the coexpression of an immortalizing
      oncogene, such as the E1A region of adenovirus. We have previously shown that
      immortalization of primary epithelial cells by E1A 12S requires the expression of
      five regions encoded by both the first and second exons of the gene. However,
      only three of these regions, located in the first exon, are required for
      cotransformation of primary cells with an activated ras oncogene. Thus, the
      expression of oncogenic ras is able to abrogate the need for the E1A function(s)
      encoded by the second exon that are required for immortalization. This suggested
      the possibility that the functions encoded by the second exon of E1A may involve
      or interact with the normal ras signal transduction pathway. The results
      described herein demonstrate that immortalization-competent 12S gene products
      induce the expression of a novel 110 kD protein, p110, that forms a stable
      complex with rasGAP. Failure to induce the p110-rasGAP complex results in the
      concomitant loss of ability of 12S to immortalize primary epithelial cells. The
      appearance of this complex parallels the expression of the 12S protein and is
      sensitive to the levels of E1A 12S. p110 induction is independent of the ability
      of 12S to activate the cell cycle and of the presence of adenovirus E1B and is
      not observed in the presence of the large T antigen of SV40. Thus, it is not a
      general response to proliferation or tumorigenic transformation, but rather seems
      to be specific to the immortalization function(s) of E1A 12S.

PMID- 9000142
TI  - Frequent microsatellite instability in post hepatitis B viral cirrhosis.
AB  - The molecular basis of cirrhosis, the most frequent underlying liver disease in
      hepatocellular carcinoma, remains unclear. We investigated microsatellite
      instability at six different loci on chromosomes 2p, 3p, 5q, 9p, 13q and 17p, in
      DNA from 38 cirrhotic livers of viral (n=28) and nonviral (n=10) origin. Sixty
      percent of the patients exhibited microsatellite alterations in at least one
      chromosome locus. A striking feature was the close association between genomic
      instability and cirrhosis linked to hepatitis B viral infection (P<0.01). This
      high instability may be a clue to the etiology of cancer induced by the hepatitis
      B virus.

PMID- 9000143
TI  - Ras-responsiveness of the HIV-1 LTR requires RBF-1 and RBF-2 binding sites.
AB  - Lentiviruses characteristically form latent integrated proviruses whose
      transcription can be induced by cell regulatory signals. The HIV-1 LTR responds
      to multiple signals, including the Ras pathway. We report here that Ras
      responsive HIV-1 transcription requires two previously undescribed factors, RBF-1
      and RBF-2 in Jurkat T cells. RBF-1 binds to Ets-like motifs located between
      nucleotides -151 and -142, and within the NF-kappaB binding sites, but is
      distinct from Ets-1 or Elf-1. RBF-2 binds the HIV-1 LTR at nucleotides -131 and 
      121 and immediately 3' of the TATA box. Both RBF-1 and RBF-2 contain DNA binding
      subunits of relative molecular weight 100 kilodaltons. Mutation of the RBF-1 and
      RBF-2 binding elements (RBEs) prevents Ras stimulation of HIV-1 LTR-directed
      transcription. These data define a mechanism for Ras responsiveness of HIV-1
      transcription that involves the previously uncharacterized factors RBF-1 and RBF
      2.

PMID- 9000144
TI  - Glucose-regulated stresses cause decreased expression of cyclin D1 and
      hypophosphorylation of retinoblastoma protein in human cancer cells.
AB  - Glucose-regulated stress response of cancer cells occurs during the growth of
      solid tumors and is induced in culture by treatments with various agents,
      including 2-deoxyglucose, glucosamine, and calcium ionophore A23187. We
      previously reported that the three stressors commonly induced cell-cycle arrest
      in the G1 phase and resistance to antitumor drugs in human cancer A2780 and HT-29
      cells. In this study, we investigated the mechanisms of stress-induced G1 arrest
      by determining the expression of cell-cycle-regulating proteins. Among G1 cyclins
      and cyclin-dependent kinases (cdk) examined, the expression levels of cyclin D1
      preferentially decreased in the stressed cells. A time-course study showed that
      the decrease in cyclin D1 coincided with the appearance of hypophosphorylated
      retinoblastoma protein (pRb), which is the growth suppressive form. These
      findings suggest that the stress-induced G1 arrest is mediated through the down
      regulation of cyclin D1-associated kinases (cdk4/6), pRb kinases during G1 phase.
      This was also supported by decreased cdk4 expression in stressed HT-29 cells. In
      addition, p21WAF1, a cdk inhibitor, was induced in the stressed cells,
      particularly A23187-treated cells. A23187, compared with the other stressors,
      caused extreme pRb hypophosphorylation, suggesting that p21WAf1 is involved in
      the regulation of pRb phosphorylation in the stressed cells. Our present findings
      could explain a molecular-based mechanism of a growth-arrested quiescent state
      and also resistance to chemotherapy of solid tumor cells.

PMID- 9000145
TI  - Analysis of the ATM protein in wild-type and ataxia telangiectasia cells.
AB  - Ataxia telangiectasia (A-T) is a human disorder that results in a number of
      clinical symptoms, including cerebellar degeneration and increased cancer
      predisposition. Recently the gene that is defective in A-T has been cloned and
      designated ATM. Here, we describe the production of antisera raised against the
      approximately 350 kDa ATM protein. Antisera specificity is confirmed by them
      recognising a approximately 350 kDa polypeptide in wild-type cells but not in A-T
      cells containing mutations that truncate ATM upstream of the antibody binding
      sites. We show that ATM is almost exclusively nuclear and is expressed in all
      cell lines and tissues analysed. However, ATM levels are not regulated in
      response to u.v. or ionising radiation. These data are consistent with ATM being
      a component of the DNA damage detection apparatus rather than being an inducible
      downstream effector of the DNA damage response. In addition, we analyse ATM
      protein expression in a variety of A-T patients. Strikingly, ATM expression is
      reduced drastically or absent in all patients analysed, including those predicted
      to express proteins that should be detected by our antisera. Thus, the A-T
      phenotype may result not only from mutations that disrupt functional domains of
      ATM, but also from mutations that destabilise the ATM mRNA or protein. Finally,
      we report that a group of patients displaying an intermediate A-T phenotype
      express low levels of apparently full-length ATM. This suggests that the ATM
      pathway is partially active in these individuals and that there is a correlation
      between levels of residual ATM expression and disease severity.

PMID- 9000147
TI  - Inverse correlation between RER+ status and p53 mutation in colorectal cancer
      cell lines.
AB  - The high point mutation rate of replication error-prone (RER+) cells could
      theoretically lead to inactivation of the p53 gene by polyclonal mutations, which
      might explain the conflicting results that have been published on the p53 status
      of RER+ colon cancers. To address this issue, we tested the p53 status of 21
      human colorectal cancer cell lines, including four showing microsatellite
      instability (RER+ phenotype). Denaturing gradient gel electrophoresis (DGGE)
      followed by sequencing showed that all four RER+ cell lines were wild type for
      p53 while 15 of the 17 RER- cell lines contained p53 mutations (P=0.001). Eight
      cell lines (four RER+ and four RER-) were analysed using three complementary
      methods to test more rigorously the polyclonal mutation hypothesis. (i) Of 87
      single-cell clones (seven to 14 per cell line) examined by DGGE, only those
      derived from known p53 mutant cell lines showed altered profiles. (ii) Antibody
      DO-7 stained more than 80% of nuclei from the p53 mutant cell lines, but only 15%
      of nuclei from the RER+ cell lines. (iii) A yeast functional assay which can
      simultaneously detect polyclonal mutations at over 500 different sites in the p53
      cDNA scored all four RER+ cell lines as containing only transcriptionally active
      p53. These data thus do not support the polyclonal mutation hypothesis and
      instead suggest that mismatch repair deficiency provides a p53-independent
      pathway for development of colorectal cancers.

PMID- 9000146
TI  - Phenotypic changes induced by wild type and variant c-src genes carrying C
      terminal sequence alterations.
AB  - We previously reported the isolation of PR2257, a novel avian sarcoma retrovirus
      which transduced the c-src protooncogene. The v-src gene of PR2257 differs from
      the c-src gene by a sequence change after amino acid 525, resulting in the
      replacement of tyrosine 527 by a valine, and an extension of the open reading
      frame into the non coding region of c-src. We investigated the respective roles
      of Tyr527 mutation and of the C-terminal extension in activating the oncogenic
      properties of c-src. Therefore we overexpressed the wild type c-src gene and c
      src variants, carrying either a substitution of tyrosine 527 or an extension of
      the C-terminus or both modifications in combination, in chicken embryo
      fibroblasts and post mitotic neuroretina (NR) cells, using replication defective
      retroviruses. We also used in vivo inoculation of plasmid DNA to assess the
      tumorigenicity of the various c-src genes. We report that, in contrast to
      previous results, overexpression of c-src is sufficient to induce NR cell
      division. While mutation of tyrosine 527 alone significantly activates c-src
      transforming and tumorigenic properties, its combination with the C-terminal
      extension of PR2257 confers to this gene full oncogenic properties and increased
      metastatic potential as compared to the v-src of Rous sarcoma virus strains.

PMID- 9000148
TI  - A transcript exhibiting homology to endogenous rat retroviral-like elements is
      regulated by p53.
AB  - Rat embryo fibroblasts transformed with HPV-16 E7 and the Ha-ras oncogene (ER
      clones) fall into two distinct groups based on their endogenous p53 status, wild
      type or mutant. We have taken advantage of such clones in order to study the p53
      target genes by the differential display method of RNA fingerprinting. We have
      identified a cDNA clone, clone 16, that recognises a large transcript on Northern
      blots. The clone 16 transcript is overexpressed in ER cell lines that express
      wild-type p53 compared with ER cell lines that express mutant p53. Similar to the
      waf1/p21 gene, which is transcriptionally activated in cells treated with
      ionizing radiation in a p53-dependent manner, the clone 16 transcript was also
      induced in response to cell irradiation. The sequence of clone 16 exhibits a high
      homology to two members of RAL retroviral-like elements.

PMID- 9000149
TI  - Allelotyping of all chromosomal arms in invasive cervical cancer.
AB  - The best characterized factor in the development of cervical cancer is the
      integration, of human papillomavirus into cervical cell chromosomes. In addition
      to HPV integration, the neoplastic process probably requires the activation of
      cellular protooncogenes and loss of tumor suppressor gene function. Loss of
      heterozygosity analysis in a large sample is used to identify regions which
      harbor putative tumor suppressor genes (TSG) since the deletion of normal alleles
      unmask mutated alleles. We evaluated tumor tissue from invasive cervical
      carcinomas, carefully microdissected to eliminate normal stroma and lymphocytes,
      for LOH at all 41 chromosomal arms with 50 polymorphic markers. We have evaluated
      tumor and normal DNA pairs from 48 invasive cervical cancers of which 85% of the
      tumors are confined to the cervix. The mean loss for all chromosomal arms was
      12%. Three regions exhibited LOH two standard deviations above the mean: 3p14.1
      12 (40%), 11q23.3 (36%), and 6p22-21.3 (32%). Three regions showed loss one
      standard deviation above the mean: 19q13.4 (30%), 6q21-23.33 (25%), and 2q33-37
      (24%). Our results indicate that a significant number of invasive cervical
      cancers have lost specific chromsomal regions, thereby suggesting that genes
      involved in the cell cycle regulation or the suppression of tumor development are
      located in these regions.

PMID- 9000150
TI  - Assessment of metabolic response and functional changes after anterior cruciate
      ligament surgery.
AB  - The main purpose of this study was to investigate metabolic changes after
      anterior cruciate ligament reconstruction and to find out whether the statements
      on training intensity in the literature can also be applied to patients in
      rehabilitation. Twenty-four male patients, 16 wk (range: 11-21 wk) postoperative,
      volunteered to participate in the study. A new four-stage test with constant time
      and load increments on the legpress in the closed kinetic chain (CKC) was
      performed. Evaluative variables were the aerobic and anaerobic threshold, force
      at exhaustion, and the maximum strength. Besides the four-stage test, the other
      parameters evaluated were functional tests (one-legged single hop, one-legged
      triple hop), rating scales (Lysholm, subjective feeling scale), thigh
      circumference, peak torque (PT), work and explosive force in the open kinetic
      chain (OKC), and muscle activity via electromyographic examination. Positive
      correlations were established for the maximum force in the CKC and PT (P < 0.01)
      and maximum force in the CKC and the thigh circumference (P < 0.05). The Lysholm
      score correlated with the anaerobic threshold (P < 0.05) and with the functional
      tests (P < 0.01). Further correlations were established between the PT and the
      work (P < 0.05) and between the single hop and the triple hop (P < 0.001). While
      the maximum force of the uninvolved leg was significantly higher than that of the
      involved leg (P < 0.01), the forces measured at termination and at the aerobic
      and anaerobic threshold (given as percent of maximum force) were significantly
      higher in the involved leg (P < 0.01). It seems that the oxidative potential
      increases or remains constant in this phase of rehabilitation and therefore the
      intensity of strength training must be adapted to the needs of the patient. Our
      easy-to-perform method makes it possible to establish an optimal intensity of
      training.

PMID- 9000151
TI  - Inhibition of histamine release by nedocromil sodium reduces exercise-induced
      hypoxemia in master athletes.
AB  - During exercise in highly-trained older master athletes (MA), the impairment of
      pulmonary gas exchanges has been shown to be associated with a concomitant
      increase in histamine release (2). To determine the role of the histamine
      released (% H) during exercise-induced hypoxemia, seven MA (age 63.2 yr +/- 1.9),
      all of whom were known to develop exercise-induced hypoxemia, performed two
      maximal incremental exercise tests at a one-month interval after administration
      of nedocromil sodium (which inhibits histamine and other mediator release) or
      placebo in random double-blind order. During exercise testing, blood samples for
      arterial blood gas analysis and histamine assay were drawn at rest, exercise and
      recovery. Nedocromil sodium induced an inhibition in % H (0.57 +/- 0.03 at
      maximal load (Pmax) with placebo vs 0.24 +/- 0.02 with nedocromil sodium) linked
      with an improvement of pulmonary gas exchange (PaO2: 71.1 +/- 1.4 at Pmax with
      placebo vs 83.4 +/- 3 with nedocromil sodium; D(Ai-a)O2: 37.5 +/- 1.4 at Pmax vs
      19.1 +/- 3.1, respectively). These results confirm the link established between
      the increase in histamine and exercise-induced hypoxemia in master athletes.

PMID- 9000152
TI  - Effect of a high or a low fat diet on cardiovascular risk factors in male and
      female runners.
AB  - Dietary fat may be associated with coronary heart disease (CHD). Studies suggest
      that restricting fat intake may compromise endurance performance and that
      increasing fat intake may improve endurance performance. We studied the effects
      of varying dietary fat intake on CHD risk factors in runners. Twelve male and 13
      female runners increased fat from 16% to 30% of daily calories (4 wk each). Of
      this group, six males and six females increased fat to 42% of daily calories (4
      wk). Physiological and lipoprotein risk factors were measured after each diet.
      Results were analyzed by repeated measures ANOVA. Increasing dietary fat from 16%
      to 42% of daily calories did not change adiposity, weight, heart rate, blood
      pressure, serum triglycerides, total cholesterol, LDL cholesterol. Apolipoprotein
      B, or the Apo A1/Apo B ratio. Compared with those eating higher fat, subjects
      eating 16% fat had lower HDL cholesterol (50 +/- 3 vs 62 +/- 3 mg.dl-1, P <
      0.0001) and Apolipoprotein A1 (111 +/- 6 v. 134 +/- 6 mg/dl, P < 0.0005) and a
      higher TC/HDL-C ratio (4.05 +/- 0.27 vs 3.42 +/- 0.24, P < 0.0005). Runners who
      increased fat intake to 42% further raised HDL cholesterol (64 +/- 6 to 69 +/- 5
      mg.dl-1, P < 0.04) without adversely affecting other lipoproteins. In conclusion,
      a 42% fat diet maintained favorable CHD risk factors in female and male runners
      whereas a 16% fat diet lowered Apo A1 and HDL-C and raised the TC/HDL-C ratio.

PMID- 9000153
TI  - The influence of baseball modulus and mass on head and chest impacts: a
      theoretical study.
AB  - Although not common, injuries that result in death do occur in youth baseball.
      Specifically, in the 5- to 14-year old age group a total of 68 deaths between
      1973 and 1995 have been directly attributed to impacts from baseballs to the head
      and chest. The purpose of this work was to determine the effect of lowering ball
      modulus and ball mass on the likelihood of reducing impact injury. A theoretical
      model, based upon the assumption of ideal elastic behavior, was used to calculate
      the impact response of the head. At a constant ball velocity, lowering both
      modulus and mass had the greatest influence in decreasing peak head acceleration,
      Gadd Severity Index, and Head Injury Criterion. Independently lowering the
      modulus or the mass decreased the impact variables and the estimates of injury,
      but the decreases varied with the specific impact variable and injury criterion.
      To study the impact response of the ball and chest, an existing viscoelastic
      lumped-element model of the chest was used. Lowering ball modulus and mass had
      various effects, e.g., lowering ball modulus did not affect peak sternal
      displacement, but it did decrease peak sternal velocity. These theoretical models
      aid in illustrating that impact response depends upon ball modulus and mass, the
      physical properties of the target, and the specific impact variable studied. This
      theoretical model suggests that a softer and lighter than traditional baseball
      would be the most likely ball model to minimize impact injuries because this ball
      consistently reduced all impact response variables studied. Since impact injury
      criteria for youths are presently not validated, the degree to which impact
      injuries may be reduced remains uncertain.

PMID- 9000154
TI  - Simulated weightlessness to induce chronic hypoactivity of brain norepinephrine
      for exercise and stress studies.
AB  - Although research on the relationship between exercise training and physiological
      stress reactivity is increasing, we know little about the involvement of brain
      neurochemistry. Moreover, the few studies that have been performed have
      concentrated on animals with normally functioning neurochemistry exposed to an
      acute stressor. Biomedical research is drawing an association between
      hypoactivation of the physiological stress response and certain medical
      conditions. As such, there is a need for an animal model that manifests a chronic
      hypoactivity of the stress system. In this report we describe the results from
      studies on norepinephrine changes with actual and simulated weightlessness in
      animals and humans. There is consistent evidence with rats that 14 d of simulated
      weightlessness produces reduced norepinephrine turnover in selected brainstem
      nuclei and peripheral tissue mediating the physiological stress response. Little
      is known about other brain regions, particularly the hypothlamus. These
      preliminary data suggest that simulated weightlessness is one method by which a
      chronic hypoactivity of norepinephrine biosynthesis or release might be induced
      to study exercise training as an intervention.

PMID- 9000155
TI  - Possible mechanisms of central nervous system fatigue during exercise.
AB  - Fatigue of voluntary muscular effort is a complex phenomenon. To date, relatively
      little attention has been placed on the role of the central nervous system (CNS)
      in fatigue during exercise despite the fact that the unwillingness to generate
      and maintain adequate CNS drive to the working muscle is the most likely
      explanation of fatigue for most people during normal activities. Several
      biological mechanisms have been proposed to explain CNS fatigue. Hypotheses have
      been developed for several neurotransmitters including serotonin (5-HT; 5
      hydroxytryptamine), dopamine, and acetylcholine. The most prominent one involves
      an increase in 5-HT activity in various brain regions. Good evidence suggests
      that increases and decreases in brain 5-HT activity during prolonged exercise
      hasten and delay fatigue, respectively, and nutritional manipulations designed to
      attenuate brain 5-HT synthesis during prolonged exercise improve endurance
      performance. Other neuromodulators that may influence fatigue during exercise
      include cytokines and ammonia. Increases in several cytokines have been
      associated with reduced exercise tolerance associated with acute viral or
      bacterial infection. Accumulation of ammonia in the blood and brain during
      exercise could also negatively effect the CNS function and fatigue. Clearly
      fatigue during prolonged exercise is influenced by multiple CNS and peripheral
      factors. Further elucidation of how CNS influences affect fatigue is relevant for
      achieving optimal muscular performance in athletics as well as everyday life.

PMID- 9000156
TI  - Effects of acute physical exercise on central serotonergic systems.
AB  - This paper reviews data concerning the effects of acute physical exercise
      (treadmill running) in trained rats. Works from the 1980's have established that
      acute running increases brain serotonin (5-hydroxytryptamine: 5-HT) synthesis in
      two ways. Lipolysis-elicited release of free fatty acids in the blood compartment
      displaces the binding of the essential amino acid tryptophan to albumin, thereby
      increasing the concentration of the so-called "free tryptophan" portion, and
      because exercise increases the ratio of circulating free tryptophan to the sum of
      the concentrations of the amino acids that compete with tryptophan for uptake at
      the blood-brain barrier level, tryptophan enters markedly in the brain
      compartment. However, this marked increase in central tryptophan levels increases
      only to a low extent brain 5-HT synthesis, as assessed by the analysis of 5
      hydroxyindoleacetic acid levels, thereby suggesting that exercise promotes
      feedback regulatory mechanisms. Indirect indices of 5-HT functions open the
      possibility that acute exercise-induced increases in 5-HT biosynthesis are
      associated with (or lead to) increases in 5-HT release. Lastly, the hypothesis
      that training and/or acute exercise triggers changes in 5-HT receptors has been
      examined in several studies; actually, both positive and negative results have
      been reached. Taken together, all these data support the need for future studies
      on the functional effects of exercise on 5-HT, including those related to the
      hypothesis that the positive mood effects of exercise rely (partly or totally) on
      central serotonergic systems.

PMID- 9000157
TI  - Brain monoamines, exercise, and behavioral stress: animal models.
AB  - This paper summarizes our studies examining whether changes in levels of brain
      monoamines after chronic exercise are associated with altered behavioral and
      endocrine responses to stressors other than exercise. The focus is on using
      animal models relevant for understanding reports by humans that regular physical
      activity reduces depression and anxiety. We studied the effects of chronic
      activity wheel running or treadmill exercise training on levels of norepinephrine
      (NE) measured in brain cell bodies and terminal regions at rest and after
      behavioral stress. We also measured brain levels of serotonin, i.e., 5
      hydroxytryptamine (5-HT), dopamine (DA), and gamma aminobutyric acid (GABA),
      which function as both antagonists and synergists with NE. In general, we found
      that chronic activity wheel running increased NE levels in the pons medulla at
      rest and protected against NE depletion in locus coeruleus cell bodies after
      footshock; the concomitant reduction in escape-latency was consistent with an
      antidepressant effect. Wheel running also decreased the density of GABAA
      receptors in the corpus striatum while increasing open-field locomotion,
      consistent with an anxiolytic effect, but had no effect on hypothalamic-pituitary
      adrenal cortical response to footshock measured by plasma levels of
      adrenocorticotropic hormone (ACTH), corticosterone, and prolactin. In contrast,
      treadmill exercise training increased the metabolism of NE in brain ascending
      terminal areas for NE, increased the secretion of ACTH after footshock and
      immobilization stress and had no effect on GABAA receptor density or open field
      locomotion. The validity of animal models for studying depression and anxiety
      after forced versus voluntary exercise is discussed. Recommendations are offered
      for improving the methods used in this area of research.

PMID- 9000158
TI  - Age and cardiac output during cycle exercise in thermoneutral and warm
      environments.
AB  - To determine whether chronological age, independent of changes in aerobic
      capacity, alters cardiac output (Qc), the central hemodynamic responses to
      intermittent incremental cycle exercise were studied in two groups of men. Qc was
      measured at rest and during exercise at 35%, 60%, 75%, and 85% peak aerobic
      capacity (VO2peak) using a CO2 rebreathing method in seven trained older (65 +/-
      2 yr) and eight normally active but untrained young men (26 +/- 1 yr) matched for
      VO2peak and anthropometric measures. Subjects were tested in both a thermoneutral
      (22 degrees C) and a warm (36 degrees C) environment to investigate possible
      differential cardiovascular responses to exercise in the heat. Only subjects with
      no history of pulmonary, cardiac, neuromuscular, or endocrine disease and a
      normal electrocardiogram were studied. The older men had significantly lower (P <
      0.05) Qc relative to the younger men at intensities greater than 60% VO2peak in
      both environmental conditions. At these higher intensities, the older men had a
      significantly higher stroke volume (SV) and lower heart rate (HR) (P < 0.05). A
      higher arteriovenous oxygen difference ((a-v)O2)) compared with their younger
      counterparts enabled the older men to exercise at the same absolute intensity,
      most likely because of training induced changes in left-ventricular performance
      and oxygen extraction. The addition of an exogenous heat source did not alter the
      Qc response in either group of men; however, a higher HR (P < 0.05) and smaller
      SV (P > 0.05) were observed in the young men during exercise in the heat. This
      may reflect previously reported differences in the skin blood flow response of
      VO2peak-matched young and older men during exercise. It is suggested that
      endurance trained older men can enhance left-ventricular performance to augment
      SV, but not sufficiently to maintain Qc in light of an attenuated HR response
      during exercise at intensities above 60% VO2peak.

PMID- 9000159
TI  - Ethnic and age trends for body composition in women residing in the U.S.
      Southwest: I. Regional fat.
AB  - The study described regional fat distribution and anthropometric variables in an
      ethnically diverse sample of women (N = 143) who were between 20 and 30
      (premenopausal) or 40 and 50 (perimenopausal) yr of age and of normal weight for
      height. Measurements included 11 skinfolds (abdomen, biceps, calf, forearm,
      midaxillary, pectoral, subscapular, suprailiac, suprapatellar, thigh, and
      triceps), waist and hip circumferences, height and mass. Regional fat
      distribution for African American, Mexican American, and Caucasian women was
      described as gluteal femoral. African American women had the smallest waist-to
      hip ratio, with larger absolute measures for both the waist and gluteal C than
      the Caucasians or Mexican Americans. Native American women had an abdominal fat
      distribution pattern which was explained by more fat on the abdomen rather than
      less fat on the gluteal-femoral area. Native Americans had a different fat
      distribution from the other ethnic groups. Caucasians are not a good comparison
      group for African Americans or Native Americans because there are large
      differences as indicated by effect sizes in regional fat distribution. Variation
      within the ethnic groups was larger than differences between the groups for most
      variables. The distribution within ethnic groups was biased by extreme scores;
      thus 50-70% of the subjects were similar regardless of ethnic group.

PMID- 9000160
TI  - Ethnic and age trends for body composition in women residing in the U.S.
      Southwest: II. Total fat.
AB  - This study assessed body density (BD) in an ethnically diverse sample of women
      (African American, Caucasian, Mexican American and Native American) (N = 139) who
      were between 20 and 30 or 40 and 50 yr of age and of normal weight for their
      height. BD was assessed using three methods: hydrostatically determined density
      (UWW), total body potassium (TBK) and the Jackson et al. (1980) sum of seven SF
      with gluteal circumference (SF). Ethnic differences in BD were detected by TBK
      and UWW. BD from SF did not detect ethnic differences, and the SEE was
      unacceptable. Based on multiple regression, the prediction equation was: BD =
      1.1197794 - 0.000224382 (X3) + 0.006999 (e2) - 0.000320177 (X2) - 0.001892 (e1) +
      0.001750 (e3) - 0.000537005 (x1) (where x1 = gluteal C, x2 = age in years, x3 =
      sum of 7 SF and e1, e2, and e3 describe ethnicity). This formula had a reduced
      SEE, a higher correlation with hydrostatically determined BD, and was sensitive
      to ethnic differences detected with other measures of BD. A 24-mmol decrease in
      potassium was found when comparing the older Caucasian women with the younger
      Caucasian women, while the difference for the African, Mexican, and Native
      American groups was 200-300 mmol.

PMID- 9000161
TI  - Family size and age at menarche in athletes.
AB  - The association between family size and age at menarche was evaluated in 370
      university athletes representing seven sports, 291 white and 79 black. Age at
      menarche, number of children in the family (family size), and birth order were
      collected retrospectively by questionnaire with a follow-up interview if
      necessary. The effect of family size on menarche was estimated with linear
      regression and multiple regression. For each additional sibling in the family-age
      at menarche was later by 0.17 yr in white athletes, 0.21 yr in black athletes,
      and 0.16 yr in the total sample (about 2.0-2.5 months). The slopes for white
      (beta = 0.167) and black (beta = 0.208) athletes did not differ significantly.
      Controlling for the effects of birth order significantly increased the family
      size effect in white athletes (beta = 0.221), but not in black athletes (beta =
      0.203) or in the total sample (beta = 0.164). The slopes for white and black
      athletes, after controlling for birth order, also did not significantly differ.
      Thus, after controlling for birth order, menarche was later by 0.16-0.22 yr
      (about 2.0-2.6 months) for each additional sibling in the family, which was
      within the range of family size effects observed in samples of nonathletes and
      athletes. The family size effect also persists after controlling for maternal age
      at menarche in a subsample of 134 athletes, thus implying an independent effect
      of family size. Later ages at menarche observed in athletes may thus be due in
      part to larger family sizes.

PMID- 9000162
TI  - Greater cross education following training with muscle lengthening than
      shortening.
AB  - The hypothesis was tested that the magnitude of cross education is greater
      following training with muscle lengthening than shortening. Changes in
      contralateral concentric, eccentric, and isometric strength and vastus lateralis
      and biceps femoris surface electromyographic (EMG) activity were analyzed in
      groups of young men who exercised the ipsilateral quadriceps with either
      eccentric (N = 7) or concentric (N = 8) contractions for 36 sessions over 12 wk.
      Control subjects (N = 6) did not train. Concentric training increased concentric
      strength 30% and isometric strength 22%, and eccentric training increased
      eccentric strength 77% and isometric strength 39% (all P < 0.05). Eccentric
      training improved eccentric strength three times more than the concentric
      training improved concentric strength (P < 0.05), and eccentric compared with
      concentric training improved isometric strength about 2 times more (P < 0.05).
      The eccentric group improved significantly from pre- to mid-training in eccentric
      and isometric strength (P < 0.05). The control group showed no significant
      changes (P < 0.05). Surface EMG activity of the vastus lateralis increased 2.2
      times (pre- to mid-training), 2.8 (mid- to post-training) and 2.6 more (pre- to
      post-training) (P < 0.05) in the eccentric than concentric group. No significant
      changes in EMG activity occurred in the control group (P > 0.05). It was
      concluded that the greater cross education following training with muscle
      lengthening is most likely being mediated by both afferent and efferent
      mechanisms that allow previously sedentary subjects to achieve a greater
      activation of the untrained limb musculature.

PMID- 9000163
TI  - Responses to exercise at the velocity associated with VO2max.
AB  - The purpose of this study was to assess the significance of the velocity at which
      an individual achieves VO2max in an incremental treadmill test (Vmax) and the
      time that this velocity can be sustained (Tmax) to evaluate the rationale for
      using Vmax and Tmax in the prescription of endurance exercise training. Mean (+/-
      SD) values for VO2max, and Vmax in 13 female track athletes were 52.1 +/- 5.1
      ml.kg.min-1 and 271 +/- 18 m.min-1, respectively. Then each athlete performed an
      exhaustive run at her Vmax. In these runs, VO2max was achieved after 234 +/- 49 s
      and was maintained for 56 +/- 48 s (range, 10-155 s) which was the last 18 +/-
      13% (range, 4-47%) of the total exercise bout. Only one of the 13 subjects
      reached VO2max in the first 60% of the constant velocity test. Thus, while VO2max
      was attained during exhaustive exercise at Vmax, the amount of time that it was
      sustained was quite small (less than 60 s) and highly variable. It was concluded
      that Vmax is a suitable intensity to elicit VO2max in training. But 60% (or less)
      of Tmax is not an appropriate duration for training at this intensity because it
      is too short a time to allow most athletes to reach VO2max.

PMID- 9000164
TI  - Effects of oral and intravenous rehydration on ratings of perceived exertion and
      thirst.
AB  - The purpose of this investigation was to compare the effects of oral and
      intravenous saline rehydration on differentiated ratings of perceived exertion
      (RPE) and thirst. Eight men underwent three randomly assigned rehydration
      treatments following a 2- to 4-h exercise-induced dehydration bout to reduce body
      weight by 4%. Treatments included 0.45% saline infusion (i.v.), 0.45% saline oral
      ingestion (ORAL), and no fluid (NF). Following rehydration and rest (2 h total),
      subjects walked at 50% VO2max for 90 min at 36 degrees C (EX). Central RPE during
      ORAL was lower (P < 0.05) than i.v. and NF throughout EX. Local RPE during NF was
      higher (P < 0.05) than i.v. and ORAL at minutes 20 and 40 of EX and overall RPE
      during NF was higher (P < 0.05) than ORAL at minutes 20 and 40 of EX. Significant
      correlations were found between overall RPE and mean skin temperature for i.v. (r
      = 0.72) and NF (r = 0.75), and between overall RPE and thirst ratings for i.v. (r
      = 0.70). Thirst ratings were not different among trials at postdehydration.
      Following rehydration, thirst was higher (P < 0.05) during NF than i.v. and ORAL
      and lower (P < 0.05) during ORAL than i.v. at all subsequent time points. Results
      suggest that oral rehydration is likely to elicit lower RPE and thirst ratings
      compared with intravenous rehydration.

PMID- 9000165
TI  - Monitoring high-intensity endurance exercise with heart rate and thresholds.
AB  - Ventilatory and lactate thresholds have been proposed as tools to establish the
      highest steady-state intensity sustainable during prolonged physical exercise.
      The purposes of this study were to clarify whether the intensity at the
      ventilatory threshold could be sustained during prolonged high-intensity exercise
      and if the corresponding work rate, pulmonary ventilation, and blood lactate
      concentration could also be maintained. Fifteen young and healthy male subjects
      were submitted to a VO2max test on ergocycle and a 90-min high-intensity
      ergocycle endurance exercise test. During the 90-min exercise test, subjects were
      able to maintain an intensity corresponding to a heart rate 5 beats.min-1 lower
      than that predetermined from the ventilatory threshold. Heart rate, FeO2, and
      FeCO2 were stable during the period from 20 to 80 min, VO2 was constant from 30
      to 80 min, while work output, pulmonary ventilation, blood lactate, and VCO2
      decreased significantly over the 90-min performance. These results show that
      physiological parameters near the ventilatory threshold are not interchangeable
      and that some cannot be used to monitor high-intensity long term exercise.
      Moreover, they clearly demonstrate that the blood lactate concentration
      fluctuates substantially during a 90-min endurance performance and cannot predict
      the highest work intensity that can be sustained during prolonged exercise
      without fatigue. However, heart rate and VO2 at the ventilatory threshold seem to
      be more suitable markers for that purpose.

PMID- 9000166
TI  - Cross validation of the 1-mile walking test for men with mental retardation.
AB  - The purpose of this study was to cross validate the equation developed by Rintala
      et al. (1992) to estimate the cardiorespiratory efficiency of men with mental
      retardation (MR). Subjects were 19 healthy men (27 +/- 8 yr) with MR (IQ = 58 +/-
      12). Following familiarization, a graded maximal treadmill test and two 1-mile
      walk tests (Rockport Fitness Walking Test, RFWT) were administered. The peak VO2
      value was the criterion measure used to cross validate the equation. The equation
      was: Peak VO2 (ml.kg-1.min-1) = 101.92 - 2.356 (MILE)-0.420 (WEIGHT). The mean
      differences were 2.04 (MILE1)(P = 0.02) and 2.43 (MILE2)(P = 0.004) ml.kg-1.min
      1. A significant positive correlation was found between measured peak VO2 and
      predicted peak VO2 on both 1-mile walks (r = 0.91 and 0.93). For both predicted
      peak VO2 values, the Total Error (TE) was greater than standard error of estimate
      (SEE), indicating a systematic difference between the measured and predicted peak
      VO2 values. Moreover, only 58% of the measured peak VO2 values fell within the
      prespecified range. Test-retest reliability of RFWT was R = 0.96. However, the
      prediction equation underestimated the actual cardiorespiratory levels in 74% and
      79% of the subjects, depending on the trial. Because the equation developed in
      this research underestimates the measured VO2 values for the majority of these
      subjects, the test is probably not statistically valid, even if reliable, and the
      prediction formula needs to be revised for this population.

PMID- 9000167
TI  - Validation of an instrument for measurement of physical activity in youth.
AB  - This study assessed the reliability and validity of the Previous Day Physical
      Activity Recall (PDPAR), a self-report instrument designed to measure physical
      activity in youth. Subjects were randomly selected students in grades 7-12. Test
      retest reliability was reported as the correlation between estimated relative
      energy expenditures determined from two PDPAR administrations completed within 1
      h. Interrater reliability was determined by two observers using the scoring
      protocol. Validity was assessed using footstrikes (pedometer), Caltrac activity
      counts, and heart rate monitoring as criterion measures. Interrater and test
      retest reliability was 0.99 and 0.98, respectively (P < 0.01). The correlation
      between relative energy expenditure from the PDPAR (kcal.kg-1.l.d-1) and
      pedometer and Caltrac counts was 0.88 (P < 0.01) and 0.77 (P < 0.01),
      respectively. The correlation between percentage heart rate range (HRmax-HR-rest)
      and mean energy expenditure from the PDPAR was 0.53 (P < 0.01). The correlation
      between 1-min heart rates > 50% HRR sustained for 20 min and the number of 30-min
      blocks with a relative energy expenditure of at least four metabolic equivalent
      tasks (MET) was 0.63 (P < 0.01). The PDPAR provides valid and reliable estimates
      of physical activity and also accurately identifies bouts of moderate to vigorous
      activity.

PMID- 9000169
TI  - Blood pressure measurement during exercise: a review.
AB  - This review summarizes research dealing with the validity of commonly used
      methods for measuring systemic blood pressure during exercise. Arterial blood
      pressures measured from within peripheral arteries exaggerate systolic blood
      pressures because of wave form reflection but provide representative mean and
      diastolic pressures of the central arterial circulation. Manual and automated
      sphygmomanometry are the best noninvasive indirect methods of blood pressure
      measurement to estimate ascending aorta systolic pressures; however, both methods
      significantly underestimate diastolic pressures at rest and during exercise. The
      error in diastolic pressure measurement increases with increasing exercise
      intensity. The accuracy of many indirect noninvasive devices for blood pressure
      measurement at rest and during exercise can be questioned because of the use of
      unsuitable criterion methods. Ascending aorta pressures should ideally be used as
      a gold standard or criterion method for blood pressure measurement during
      exercise and instrument/method validation. However, given the constraints of
      varied criterion standards and current recommendations for blood pressure
      measurement, the following units were found to be acceptable devices for
      measuring systolic blood pressure during exercise: Accutracker II, A&D TM 2421,
      Colin 630 (auscultation), Critikon 1165, and possibly the Paramed 9350.

PMID- 9000168
TI  - Simultaneous monitoring of heart rate and motion to assess energy expenditure.
AB  - Measurement of energy expenditure in free-living individuals represents a
      methodologic challenge in epidemiologic research. Heart rate monitors, while
      closely tied to energy expenditure at high levels of energy output, provide much
      less predictive power at low levels; however, measurement of motion may improve
      the predictive ability. This study was undertaken to determine the usefulness of
      simultaneously monitoring heart rate and motion for the estimation of energy
      expenditure. Ten subjects were studied during simulated activities of daily
      living (ADLC) and submaximal treadmill tests. Compared to direct measurement, the
      motion sensor predicted oxygen consumption poorly (r2 = 0.53) for both tests.
      Heart rate measured simultaneously yielded an r2 of 0.81 for ADLC and 0.90 for
      the treadmill. Addition of motion data increased the r2 value for the ADLC for
      all but one individual and increased the group mean from 0.81 to 0.86. This
      improvement was not observed for the treadmill, confirming the hypothesis that
      the principle value of monitoring motion occurs at lower heart rates.

PMID- 9000170
TI  - Mutations induced by DNA double-strand breaks: the influence of genomic site.
AB  - The transgenic CHO cell line PL61, carrying a recombinant SV40-gpt gene, was
      treated with restriction endonucleases to assess mutagenesis from defined DNA
      double-strand breaks. Mutations in gpt were measured under two conditions: a
      stringent condition where selection ensured that the closely-linked neo gene was
      retained functionally intact, or a relaxed condition without the requirement for
      neo gene function. Despite testing 18 different restriction endonucleases with
      various numbers of potential break-sites within the transgene, mutations were
      only found under relaxed selection conditions. These mutations commonly led to
      complete loss of the transgene, suggesting that large deletions predominate when
      selection is relaxed. It is argued, in comparison to mutation data for other
      genomic sites in CHO cells, that variations in the 'effective target size' for
      mutagenesis may explain the response of the transgene under different conditions.

PMID- 9000172
TI  - DNA topoisomerase II inhibitors enhance random integration of transfected vectors
      into human chromosomes.
AB  - To study the involvement of DNA topoisomerase (topo) II on nonhomologous
      (illegitimate) recombination, we examined the effect of topo II inhibitors on
      random integration of exogenous vectors into human chromosomes. We transfected
      human cell lines PA1, HeLa and EJ-1 with linearized plasmid pSV2neo by
      electroporation, treated with topo II inhibitors and determined the frequency of
      Geneticin-resistant (G418r) colonies. We found that three topo II inhibitors,
      etoposide (VP-16), ICRF-193 and amsacrine (m-AMSA), greatly enhanced the
      frequency of G418r colonies. These effects were maximally expressed by as little
      as 12 hrs treatment with the drugs. Similar enhancements were found with
      different vectors (closed-circular and linear), different cell types, or by
      different transfection methods (calcium precipitation and lipofection). In
      contrast, the inhibitor treatments did not affect the transient expression of
      chloramphenicol acetyltransferase and beta-galactosidase activity following
      transfection with pSV2CAT and pCH110, respectively. Southern blot analysis
      revealed that the integration pattern of transfected pSV2neo into PA1 chromosomes
      was random and not characteristic for each inhibitor. These results suggest that
      topo II inhibitors directly act at a nonhomologous recombination reaction,
      promoting the integration process of transfected vectors into human chromosomes.
      We discuss the enhancement mechanism with a special emphasis on DNA strand breaks
      induced by the inhibitors.

PMID- 9000171
TI  - An intron 1 regulatory region from the murine adenosine deaminase gene can
      activate heterologous promoters for ubiquitous expression in transgenic mice.
AB  - Ubiquitously expressed genes contain regulatory features which allow expression
      in virtually all cell types. In an effort to understand the molecular basis for
      this regulatory feature, the chromatin structure of the murine adenosine
      deaminase gene was examined by DNase I digestion in nuclei of several tissues.
      The promoter contained a strong hypersensitive site in all tissues examined,
      including those with very high and very low levels of ADA expression. Transgenic
      mouse studies revealed that a 3.3 kb EcoRI (3.3EE) fragment from intron I was
      required to generate a strong promoter DNase I hypersensitive site, and to
      produce ubiquitous expression. The 3.3EE fragment also contained a thymic
      enhancer activity which mapped to sequences conserved with the human ADA gene T
      lymphocyte enhancer. Mutational analysis indicated that ubiquitous expression was
      not dependent on the presence of a functional thymic enhancer. Both the thymic
      enhancer and the ubiquitous activator within the 3.3EE fragment functioned with
      heterologous promoters in transgenic mice.

PMID- 9000173
TI  - Effects of infection rate and selection pressure on gene expression from an
      internal promoter of a double gene retroviral vector.
AB  - Many commonly used retroviral vectors express one gene from the viral long
      terminal repeat (LTR) promoter and another gene from an internal promoter. We
      have investigated factors affecting the expression of the luciferase reporter
      gene from the internal cytomegalovirus-derived promoter of the retroviral vector,
      LNCX, which contains a LTR-driven neo gene as a selectable marker. A subline of
      human HT1080 cells, expressing the murine ecotropic receptor, was infected with
      retrovirus generated by transient transfection of BOSC 23 packaging cells. Mass
      populations of cells infected under conditions resulting in different initial
      infection rates (IIR) and selected with G418, showed highly variable luciferase
      activity. Luciferase expression in cell populations with IIR < or = 5% was
      generally low; many populations with IIR < 1% had marginal or no luciferase
      activity. The loss of luciferase expression in low-IIR populations was associated
      with G418 selection. In contrast, cell populations with IIR > or = 6% showed
      higher luciferase expression, which was strongly correlated with the IIR.
      Southern hybridization analysis showed that most cells of the low-IIR populations
      carried one integrated provirus, with a high incidence of structural
      rearrangements that abolished luciferase activity. In contrast, populations with
      IIR > or = 6% contained two or more copies of integrated provirus per cell, and
      their luciferase activity correlated with the provirus copy number. Luciferase
      expression was relatively stable in the populations with IIR > 1% maintained in
      the absence of G418. Increasing the selective concentration of G418 or prolonged
      maintenance of cell populations in the presence of G418 resulted in higher
      incidence of provirus rearrangements and decreased luciferase expression. These
      results indicate that the negative effect of selection for the LTR-driven gene on
      gene expression from an internal promoter depends on the selection stringency and
      can be obviated by increasing the infection rate.

PMID- 9000174
TI  - Isolation and characterization of human hepatoma cells with targeted insertions
      of a gpt selectable marker in the alpha 1-antitrypsin locus.
AB  - The bacterial xanthine-guanine phosphoribosyl transferase (gpt) gene was inserted
      by homologous recombination into the chromosomal alpha 1-antitrypsin (alpha 1AT)
      gene of HPRT-deficient human hepatoma cells. These insertions encoded chimeric
      alpha 1AT-gpt mRNAs that were expressed in the modified cells. Six targeted
      integrations were obtained, but only two of these harbored simple insertion
      events. The remaining four homologous insertions contained additional DNA
      sequences 3' of the gpt coding cassette. Variant cell lines deficient for gpt
      expression were isolated from transfectants containing either homologous or non
      homologous gpt insertions by selection in media containing 6-thioguanine. These
      variant cell lines expressed alpha 1AT but not alpha 1AT-gpt mRNAs, indicating
      that they contained expression defects in cis. Genotypic analyses suggested that
      the predominant mechanism by which the variants were generated was by
      nondisjunctive loss of chromosomes containing the modified alpha 1AT-gpt alleles.
      Somatic cell hybrids formed by fusing hepatoma cells containing targeted alpha
      1AT-gpt insertions with fibroblasts exhibited extinction of both modified and
      unmodified alpha 1AT alleles.

PMID- 9000175
TI  - Molecular comparison of cultured hybridoma cells that switch isotypes at high and
      low rates.
AB  - We have previously reported the isolation of variants from the 36.65 and PC1.4.1
      hybridoma cell lines that spontaneously switch from gamma 1 to gamma 2a and gamma
      2b at high and low rates. In order to further characterize the phenotype of these
      variants, we have now investigated the production of germline transcripts and
      methylation which are two of the molecular correlates of isotype switching. While
      some of the correlations that exist in normal cells were present in some of the
      clonal variants, others were not. However, the higher switching variants of both
      cells lines had higher recombinational activity as measured with a shuttle
      vector. The distinct phenotypic characteristics of each cell line provide an
      opportunity to dissect the roles of individual molecular events in the process of
      isotype switching.

PMID- 9000177
TI  - Computer-generated graphical presentations: use of multimedia to enhance
      communication.
AB  - Personal computers may be used to create, store, and deliver graphical
      presentations. With computer-generated combinations of the five media (text,
      images, sound, video, and animation)--that is, multimedia presentations--the
      effectiveness of message delivery can be greatly increased. The basic tools are
      (1) a personal computer; (2) presentation software; and (3) a projector to
      enlarge the monitor images for audience viewing. Use of this new method has grown
      rapidly in the business-conference world, but has yet to gain widespread
      acceptance at medical meetings. We review herein the rationale for multimedia
      presentations in medicine (vis-a-vis traditional slide shows) as an improved
      means for increasing audience attention, comprehension, and retention. The
      evolution of multimedia is traced from earliest times to the present. The steps
      involved in making a multimedia presentation are summarized, emphasizing advances
      in technology that bring the new method within practical reach of busy
      physicians. Specific attention is given to software, digital image processing,
      storage devices, and delivery methods. Our development of a urology multimedia
      presentation--delivered May 4, 1996, before the Society for Urology and
      Engineering and now Internet-accessible at http://www.usrf.org--was the impetus
      for this work.

PMID- 9000176
TI  - Isolation and characterization of HPRT-deficient human hepatoma cells.
AB  - Human hepatoma cells deficient in HPRT activity were isolated by challenging
      HepG2 cells with 6-thioguanine (6TG). Three 6TG-resistant isolates were plated in
      selective media, and each clonal line displayed an 8-azaguanine-resistant, HAT
      sensitive phenotype. The HPRT-deficient phenotype of one of these clones, H30-1,
      was confirmed in genetic tests: the HAT-sensitivity of H30-1 cells was
      complemented by fusion by HPRT+ (Ltk-) but not HPRT- (A9) cells. Furthermore,
      transfection of the bacterial xanthine-guanine phosphoribosyl transferase (gpt)
      gene into H30-1 cells rendered them HAT-resistant. H30-1 cells maintained the
      differentiated morphology, growth characteristics, fusion properties, and
      transfection efficiencies typical of parental HepG2 cells, and they expressed
      several liver-specific genes. Finally, the H30-1 cell line contained a modal
      number of 50 chromosomes. Therefore, H30-1 cells represent an HPRT-deficient
      HepG2 derivative that retains its differentiated phenotype in vitro.

PMID- 9000178
TI  - Symptom scores in benign prostatic hyperplasia.

PMID- 9000179
TI  - Determination of the "reflex range" and appropriate cutpoints for percent free
      prostate-specific antigen in 413 men referred for prostatic evaluation using the
      AxSYM system.
AB  - OBJECTIVES: Prostate-specific antigen (PSA) exists in the serum in two clinically
      important molecular forms: free PSA and PSA complexed to alpha 1
      antichymotrypsin. Total PSA approximates the sum of the free and complexed forms.
      Preliminary investigations have illustrated the potential benefits of using
      percent free PSA to enhance the clinical utility of PSA in distinguishing benign
      prostate disease from prostate cancer. The current study defines the optimal
      range of total PSA for measuring percent free PSA (reflex range) and generates
      appropriate cutpoints for percent free PSA within this range. METHODS: A total of
      413 patients, 225 (54%) with benign prostate disease (mean age, 67 years) and 188
      (46%) with prostate cancer (mean age, 66 years), who had PSA values between 2.0
      and 20.0 ng/mL participated in the investigation. All patients underwent a
      sextant biopsy to establish the diagnosis. The serum specimens were assayed with
      the AxSYM PSA assay (total PSA) and AxSYM Free PSA assay (Abbott Laboratories;
      Abbott Park, IL). Percent free PSA was calculated for all patients. Receiver
      operating characteristic (ROC) curves were generated for various ranges of total
      PSA to determine the reflex range that maximized the increase in sensitivity and
      specificity of percent free PSA over total PSA. Within the optimal range, the ROC
      curves were utilized to generate cutpoints for percent free PSA to be used in
      clinical practice. RESULTS: The appropriate reflex range for the utility of
      percent free PSA was 3.0 to 10.0 ng/mL. The appropriate cutpoint for percent free
      PSA when the total PSA value was 3.0 to 4.0 ng/mL to achieve 90% sensitivity for
      the detection of prostate cancer was 0.19. This approach resulted in a biopsy
      rate of 73% and a cancer detection rate of 44% in men with a total PSA value
      between 3.0 and 4.0 ng/mL. The appropriate cutpoint for percent free PSA when the
      total PSA value was 4.1 to 10.0 ng/mL to ensure 95% sensitivity for detection of
      prostate cancer was 0.24. Within the range of 4.1 to 10.0 ng/mL, this approach
      resulted in 13% fewer negative biopsies and failure to detect 5% of the cancers.
      CONCLUSIONS: Percent free PSA should be utilized in patients with a total serum
      PSA value between 3.0 and 10.0 ng/mL. In patients with a total PSA value between
      3.0 and 4.0 ng/mL, percent free PSA enhanced the detection of prostate cancer
      (improving sensitivity). In patients with a total PSA concentration ranging from
      4.1 to 10.0 ng/mL, negative biopsies were eliminated (improving specificity).

PMID- 9000180
TI  - Adrenal metastases from renal cell carcinoma: role of ipsilateral adrenalectomy
      and definition of stage.
AB  - OBJECTIVES: We undertook this study to establish criteria for adrenalectomy in
      patients with renal cell carcinoma. METHODS: We retrospectively reviewed the
      records of 162 patients undergoing radical nephrectomy from 1979 to 1993 at
      University Hospitals of Cleveland. Simultaneous ipsilateral adrenalectomy was
      performed in 57 patients (35%). RESULTS: Three of these 57 patients (5.3%) had
      ipsilateral adrenal metastases. All 3 patients had large, left-sided, upper-pole
      tumors that extended through the renal capsule (Stage T3a). All 3 patients with
      adrenal metastases had progression to disseminated disease, with an average time
      to progression of 7.2 months, whereas only 13 (24%) of the 54 patients without
      adrenal metastases developed metastatic disease (none to adrenal), with an
      average time to progression of 27.6 months. No patient with organ-confined
      disease (Stage T1 or T2) or extracapsular disease in the midkidney or lower pole
      had adrenal metastases identified histologically. CONCLUSIONS: The prognosis is
      poor for renal cell carcinoma with ipsilateral adrenal involvement, even with
      complete removal. Because of this poor prognosis, we believe that adrenal
      involvement should constitute a separate stage category. We propose that patients
      with ipsilateral adrenal metastases via direct extension should be classified as
      having pathologic Stage pT3d. If the patient has an ipsilateral adrenal
      metastasis not via direct extension, contralateral adrenal metastasis, or
      bilateral adrenal metastases, the pathologic stage should be M1. Ipsilateral
      adrenalectomy should only be performed if a lesion is seen preoperatively on
      computed tomographic scan or if gross disease is seen at the time of nephrectomy
      although its removal may not benefit the patient.

PMID- 9000181
TI  - Preoperative transesophageal echocardiography for assessment of vena caval tumor
      thrombi: a comparative study with venacavography and magnetic resonance imaging.
AB  - OBJECTIVES: Renal cell carcinoma extends into the inferior vena cava (IVC) in 4%
      to 10% of patients. The purpose of this study was to evaluate the diagnostic
      accuracy of preoperative transesophageal echocardiography (TEE) in determining
      the presence and level of IVC involvement in such cases. METHODS: From June 1992
      to December 1995, 13 patients with suspected IVC tumor thrombi were studied with
      preoperative TEE. These patients were also evaluated with either magnetic
      resonance imaging (MRI; n = 10), contrast venacavography (CVC; n = 8), or both of
      the latter (n = 5). All patients subsequently underwent surgical removal of the
      primary tumor and IVC thrombus. The presence and level of IVC thrombus at surgery
      was correlated with that predicted by the various preoperative imaging
      modalities. RESULTS: Preoperative TEE accurately delineated the presence and
      extent of IVC tumor thrombus involvement in 11 of 13 patients (85%); the level of
      IVC involvement was overstaged in 1 patient and understaged in 1 patient.
      Accurate diagnostic information was provided by MRI in 9 of 10 patients (90%) and
      by CVC in 6 of 8 patients (75%). CONCLUSIONS: In patients with IVC tumor thrombi,
      preoperative TEE can provide accurate information regarding the presence and
      extent of IVC involvement. However, TEE is an invasive and costly procedure with
      no diagnostic advantage over MRI in the preoperative evaluation of these
      patients.

PMID- 9000182
TI  - Role of the four-corner bladder neck suspension to correct stress incontinence
      with a mild to moderate cystocele.
AB  - OBJECTIVES: Women undergoing four-corner bladder neck suspension were evaluated
      for subjective and objective results of the procedure. Patients were evaluated
      for continence, prolapse, and symptomatic status postoperatively. METHODS: Forty
      seven women underwent four-corner bladder neck suspension for moderate cystocele
      with (44) or without (3) stress urinary incontinence. Mean and median follow-up
      were 37 months (range 15 to 80). To assess results of the four-corner bladder
      neck suspension, two sets of outcome measures were used (subjective
      questionnaire, including patient satisfaction, and objective physical
      examination, with standing voiding cystourethrogram) to compare pre- and
      postoperative data. RESULTS: At the time of follow-up, 25 patients (53%) reported
      no incontinence, 14 (30%) reported one incontinent episode per week, and 8 (17%)
      reported daily loss of urine. Twenty-seven (57%) had grade I or grade II
      cystoceles on follow-up examination and voiding cystourethrogram; however, only
      12 (26%) experienced recurrent prolapse symptomatology. Overall patient
      acceptance of the procedure was high (70%). CONCLUSIONS: The four-corner bladder
      neck suspension is an effective option in the management of moderate cystocele.

PMID- 9000183
TI  - Prospective development of a cost-efficient program for the pubovaginal sling.
AB  - OBJECTIVES: We designed and implemented a cost-containment program for patients
      undergoing a pubovaginal sling procedure. We sought to test the hypothesis that
      preoperative patient education could reduce the length of hospital stay in these
      patients. Our goal was to decrease hospital charges while maintaining quality of
      care. METHODS: A multidisciplinary group of clinic and hospital staff identified
      factors that contribute to a patient's hospital charges for a pubovaginal sling
      procedure. A program of preoperative patient education to teach intermittent self
      catheterization was combined with the elimination or control of items considered
      unnecessary to the delivery of safe, efficient care. Patient care was
      standardized from the preoperative visit to discharge planning. The difference in
      the mean values of 38 prestudy patients was compared with 15 study patients with
      a Wilcoxon rank sum test. RESULTS: Length of hospital stay was reduced from a
      mean of 2.8 to 1.1 days after implementation of the program (P < 0.0001). This
      decreased length of stay, combined with a reduction in routine laboratory studies
      (97% decrease; P < 0.0001), operating room charges (11% decrease; P < 0.01), and
      medications (35% decrease; P < 0.01), led to significantly reduced hospital
      charges. Total hospital charges decreased by 35%, from a mean of $4862 to a mean
      of $3153 (P < 0.0001). There was no increase in morbidity. Patient satisfaction
      with length of hospital stay did not change significantly following
      implementation of the program. CONCLUSIONS: With a program of preoperative
      patient education combined with a critical review of the factors contributing to
      a patient's hospital charges, it is possible to implement a cost-efficient
      program for a pubovaginal sling, leading to a 35% reduction in mean total
      hospital charges. This approach directed toward other incontinence procedures
      could be expected to yield comparative results.

PMID- 9000184
TI  - Latin American study on patient acceptance of the International Prostate Symptom
      Score (IPSS) in the evaluation of symptomatic benign prostatic hyperplasia.
AB  - OBJECTIVES: To determine the acceptance of the self-administered International
      Prostate Symptom Score (IPSS) by people of differing educational levels in two
      different countries. METHODS: The questionnaire adopted by the World Health
      Organization and known as the IPSS attempts to measure the severity of lower
      urinary tract symptoms in men with benign prostatic hyperplasia. An international
      study was performed in Brazil and Argentina and included 768 patients. The IPSS
      was self-administered and used to evaluate and quantify the clinical symptoms
      resulting from benign prostatic hyperplasia. The patients were asked not to
      answer any questions that they did not clearly understand or about which they
      were unsure of the information they should give. The patients were assessed into
      two subgroups according to their level of education. The Brazilian group
      consisted of 458 men in which subgroup 1 was composed of 244 (53%) men who had an
      elementary school education, whereas subgroup 2 consisted of 214 (47%) men who
      had a higher education level, including a university degree. The Argentinian
      group consisted of 310 patients, 158 (51%) of whom had an elementary school
      education, whereas the remaining 152 (49%) had received higher education,
      including a university degree. RESULTS: A total of 77 men (16.8%), 35 (45.5%)
      from subgroup 1 and 42 (54.5%) from subgroup 2, failed to complete the
      questionnaire. The difference between the two subgroups was not significant. A
      total of 189 questions were not answered. There was no significant difference
      among the three questions most frequently unanswered by each subgroup. A total of
      40 (12.9%) men filled out the questionnaire incompletely, 31 (77.5%) in the lower
      education subgroup and 9 (22.5%) in the higher-education subgroup. An incomplete
      questionnaire was more frequent among the patients with lower education (P <
      0.01). CONCLUSIONS: In spite of the cultural variations, there was no significant
      difference in the number of patients unable to answer the questionnaire in the
      two countries.

PMID- 9000185
TI  - Effect of transurethral indwelling catheter on serum prostate-specific antigen
      level in benign prostatic hyperplasia.
AB  - OBJECTIVES: The purpose of this prospective study was to determine the influence
      of indwelling transurethral catheters on the serum prostate-specific antigen
      (PSA) levels in patients with benign prostatic hyperplasia (BPH). We compared the
      PSA values of preoperatively catheterized and noncatheterized patients. METHODS:
      Ninety patients undergoing a prostatectomy for benign disease were included. The
      indwelling catheter (IC) group and noncatheterized (NC) group each consisted of
      45 patients. A total of 83 patients who did not have prostate carcinoma were
      analyzed by means of PSA, PSA density (PSAD), and pathologic presentations.
      Prostate pathologies that might elevate PSA values were excluded to demonstrate
      the correlation of PSA levels and standard urethral catheterization. RESULTS: A
      statistically significant relationship was determined between an indwelling
      urethral catheter and an elevated serum PSA value. The average PSA level of the
      IC group was 2.6 times that of the NC group. CONCLUSIONS: PSA, PSAD, and age
      adjusted PSA levels were elevated above normal ranges in patients with BPH who
      had an indwelling urethral catheter.

PMID- 9000186
TI  - Outcome of sextant biopsy according to gland volume.
AB  - OBJECTIVES: To reassess positive rate of sextant biopsy according to gland size.
      METHODS: We evaluated 1974 consecutive men with systematic sextant biopsy, among
      whom we examined biopsy yield according to gland-volume intervals of 10 cc.
      RESULTS: Decreasing yield of sextant biopsy is strongly associated with
      increasing gland volume (P < 0.001). Highest biopsy rate (39.6%) was recorded
      among men with prostates smaller than 20 cc. The lowest biopsy rate (10.1%) was
      recorded among men with prostates between 80 and 89.9 cc. Among men with biopsy
      proven cancer, age, serum prostate-specific antigen, and Gleason grade were
      comparable (P > 0.05) throughout the range of gland-volume intervals.
      CONCLUSIONS: Our findings suggest that gland size represents an important
      determinant contributing to the yield of sextant biopsy in men at risk of
      harboring a nonpalpable, isoechoic cancer. Consequently, an individualized sector
      biopsy approach, based on prostate volume, may warrant consideration because it
      may ensure superior detection of clinically significant disease among all men at
      risk, regardless of prostate size.

PMID- 9000187
TI  - Comparison of laparoscopic and minilaparotomy pelvic lymphadenectomy for prostate
      cancer staging in a community practice.
AB  - OBJECTIVES: To compare the cost-effectiveness and morbidity of minilaparotomy
      (MINILAP) and laparoscopic pelvic lymphadenectomy (LAP) in a community practice
      setting. METHODS: We reviewed our experience with 44 consecutive patients with
      prostate cancer who had staging pelvic lymphadenectomy from January 1992 through
      April 1995 in a general health maintenance organization urology practice. Of this
      group, 22 men had LAP and 22 men had MINILAP. RESULTS: MINILAP and LAP groups
      were similar in age (mean 67 years). Gleason score (mean 7.2 and 6.8), prostate
      specific antigen level (mean 46 and 49 ng/mL), and clinical stage (T1 to T3).
      Operative time was statistically significantly shorter for MINILAP (mean 1.2
      hours) than for LAP (mean 2.9 hours). Complication rate was 9.1% for MINILAP and
      31.8% for LAP. Lymph node metastasis was found in 45% of MINILAP patients and in
      27% of LAP patients. Mean initial hospital stay was 1.0 day for MINILAP and 1.6
      days for LAP. Total hospital stay including hospital readmission for
      complications was 1.5 days for MINILAP and 2.6 days for LAP. Cost of MINILAP was
      at least $1900 less than that of LAP because of shorter total hospital stay,
      shorter operation time, and lower equipment cost. CONCLUSIONS: Compared with LAP,
      MINILAP was more cost-effective and produced less morbidity. Patient satisfaction
      with the procedures was similar. MINILAP is an excellent alternative to LAP for
      prostate cancer staging in general urology practice.

PMID- 9000188
TI  - Irradiation for locally recurrent carcinoma of the prostate following radical
      prostatectomy.
AB  - OBJECTIVES: To evaluate the outcome of patients treated with irradiation (RT) for
      isolated, clinically apparent local tumor recurrence following prostatectomy for
      carcinoma of the prostate (CaP). METHODS: Between May 1979 and July 1992, 35
      patients received external-beam RT as sole salvage therapy for post-prostatectomy
      locally recurrent CaP. Patient outcome was evaluated through retrospective
      medical record review with respect to clinical and prostate-specific antigen
      based (that is, biochemical) control rates, as well as disease-free (clinical and
      biochemical) and overall survival estimates. Chronic RT-induced morbidity was
      also examined, and pre-RT disease characteristics were evaluated for their
      association with disease outcome. RESULTS: With median follow-up of 5.2 years
      (range 1.7 to 12.1) in survivors (30 patients), 19 patients (54%) had clinical
      (local, 1 patient [3%]; metastatic, 7 patients [20%]) or biochemical only (11
      patients [31%]) relapse. The 8-year clinical relapse-free and any relapse-free
      (clinical or biochemical) rates were 80% and 56%, respectively, whereas the
      overall survival estimate was 97%. A chronic complication(s) of treatment was
      noted in 15 patients (43%) but spontaneously resolved in all but 6 (17%);
      persistent complications were mild and associated with rectal (grade 1 to 2, 14%)
      and lymphatic (3%) systems. The interval between prostatectomy and local tumor
      recurrence, the pre-RT prostate-specific antigen serum level, the pathologic
      stage, and tumor differentiation may be associated with disease outcome.
      CONCLUSIONS: External-beam RT resulted in excellent local tumor control without
      serious long-term morbidity in most patients. Although this study could not
      define an optimal management strategy (for example, symptomatic measures only,
      RT, or hormonal therapy), these results provided outcome measures, in
      relationship to pre-RT tumor-related factors, that may be valuable for clinical
      decision-making.

PMID- 9000189
TI  - Maximum androgen blockade in advanced prostate cancer: a meta-analysis of
      published randomized controlled trials using nonsteroidal antiandrogens.
AB  - OBJECTIVES: To assess the survival benefit of maximum androgen blockade (MAB)
      using nonsteroidal antiandrogens (NSAAs) through meta-analysis of published
      randomized controlled trials (RCTs). METHODS: All RCTs comparing treatment with
      NSAA plus either luteinizing hormone-releasing hormone (LHRH) or orchiectomy
      versus treatment with LHRH or orchiectomy alone were included if the necessary
      statistical summaries were present in the publication. Estimates and standard
      errors of log hazard ratio for overall survival and progression-free survival
      were derived from published studies using two methods: (1) reconstructing an
      annual life table from graphical presentations of survival distributions and
      fitting discrete proportional hazard models, and (2) reconstructing the log
      hazard ratio from reported P values and numbers of deaths. An alternative set of
      log hazard ratios was derived from figures presented in a summary report by the
      Prostate Cancer Trialists' Collaborative Group (PCTCG). Comparative meta-analyses
      were performed using the random effects approach of DerSimonian and Laird.
      Additionally, published studies were used in a random-effects-based meta-analysis
      of objective tumor response. RESULTS: Nine studies provided enough information to
      perform a meta-analysis for survival using one of the two methods. Estimates of
      relative risks (RR) comparing treatment with NSAA plus either LHRH or orchiectomy
      versus treatment with LHRH or orchiectomy alone with respect to overall survival
      were 0.78 (95% confidence intervals [CIs] 0.67 to 0.90) using method 1, and 0.84
      (95% CI 0.76 to 0.93) using method 2. Sensitivity analyses based on PCTCG data
      showed that a favorable survival result for MAB was associated with NSAAs but not
      with steroidal antiandrogens and depended on randomization blinding and overall
      trial quality. Additionally, random-effects-based meta-analysis of published
      studies showed a significant increase in time-to-progression (RR = 0.74; 95% CI
      0.63 to 0.86) and an increase in objective tumor responses for MAB using NSAAs
      compared with castration alone (odds ratio = 0.65; 95% CI 0.51 to 0.81; P =
      0.00022). CONCLUSIONS: Inconsistent results have been published about the benefit
      of MAB in advanced prostate cancer. This meta-analysis supports a beneficial
      effect for MAB using NSAAs compared with castration alone, and sensitivity
      analyses suggest that the design of future trials should carefully address issues
      of patient characterization, randomization blinding, and other study quality
      issues.

PMID- 9000190
TI  - Intermittent androgen deprivation after PSA-complete response as a strategy to
      reduce induction of hormone-resistant prostate cancer.
AB  - OBJECTIVES: The increasing interest in exploring the use of intermittent androgen
      deprivation in prostate cancer has prompted a retrospective review of patients
      who elected to stop treatment. METHODS: Case records were reviewed. RESULTS:
      Twenty patients after 3 to 48 months (median 12) of endocrine therapy elected to
      stop therapy. Thirteen subsequently relapsed after a median observation of 9
      months. Seven of 20 patients continue progression-free for 9 to 42 months (median
      33). After second-line therapy, 75% of patients with a relapse remain progression
      free at 2 years. Progression-free survival was higher in patients at Stage M0
      (82% at 1 year) versus M+ (29% at 1 year). CONCLUSIONS: With 10 of 13 patients
      demonstrating an ongoing second PSA response, 45% of patients showing no
      progression, and 85% alive at 3 years, these results support findings from
      previous publications that suggest that there are no major risks with use of
      intermittent hormone therapy. However, in the future, there is an urgent need
      that such studies should be randomized and done in the context of audit-based
      research and development programs. The resources released could then be invested
      with respect to further improvements in treatment of prostate cancer, possibly
      considering such a combined approach with immunotherapy as an alternative to
      surgery or radiotherapy for early disease in elderly patients with long PSA
      doubling time.

PMID- 9000191
TI  - Is assisted reproduction the optimal treatment for varicocele-associated male
      infertility? A cost-effectiveness analysis.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of assisted reproduction using in
      vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) as a
      primary treatment for varicocele-associated infertility. METHODS: Analysis of
      cost per delivery using published and contemporary results for treatment with
      ICSI in the United States for male factor infertility was compared with cost per
      delivery after surgical varicocelectomy. Only results from controlled trials of
      varicocelectomy were used for evaluation of pregnancy and delivery rates. Cost
      estimates were based on prevailing nationwide charges for services in 1994.
      RESULTS: The cost per delivery with ICSI was found to be $89,091 (95% confidence
      interval $78,720 to $99,462), whereas the cost per delivery after varicocelectomy
      was only $26,268 (95% confidence interval $19,138 to $44,656). Assuming the
      highest possible published success rate for ICSI resulted in a cost estimate as
      low as $62,263. The average published U.S. delivery rate after one attempt of
      ICSI was only 28%. whereas a 30% delivery rate was obtained after
      varicocelectomy. CONCLUSIONS: Specific treatment of varicocele-associated male
      factor infertility with surgical varicocelectomy is more cost-effective than
      primary treatment with assisted reproduction. Continued evaluation and treatment
      of the man with infertility is warranted. Despite the apparent success of ICSI
      for the most severe cases of male factor infertility, application of assisted
      reproduction for all cases of male factor infertility also does not necessarily
      provide as high a delivery rate as specific treatment of the cause of male factor
      infertility.

PMID- 9000192
TI  - Presence of mature sperm in testicular parenchyma of men with nonobstructive
      azoospermia: prevalence and predictive factors.
AB  - OBJECTIVES: Hitherto, patients with testicular dysfunction and azoospermia had to
      resort to adoption, donor sperm insemination, or child-free living. The
      realization that a proportion of such men harbor spermatozoa in their testicular
      parenchyma, combined with the ability of intracytoplasmic sperm injection (ICSI)
      to effect pregnancy with single sperm, has prompted male infertility clinicians
      to explore testicular sperm extraction (TESE) in this patient population. We
      sought to investigate the likelihood of finding spermatozoa during TESE from men
      presenting with nonobstructive azoospermia and to define if any factors existed
      that were predictive of eventual sperm presence or absence. METHODS: Thirty
      patients with nonobstructive azoospermia underwent TESE and simultaneous formal
      testis biopsy, cytologic analysis, and wet preparation analysis. Tissue obtained
      from TESE was analyzed according to a rigorous protocol, followed by exhaustive
      searching by trained embryologists. RESULTS: Twenty-one patients (70%) had
      spermatozoa found on testicular tissue analysis. Neither patient age nor follicle
      stimulating hormone (FSH) level was predictive of the ability to find sperm. With
      regard to histologic pattern, 50% of men with Sertoli cell-only, 75% of patients
      with maturation arrest, and 100% of patients with spermatids seen on histologic
      analysis had sperm retrieved from their testicular tissue during TESE. Absence of
      sperm on cytologic smear and wet preparation analysis failed to predict the
      presence of sperm on formal testicular tissue analysis in 40% of patients.
      CONCLUSIONS: Men with nonobstructive azoospermia may have mature spermatozoa
      present within their testicular parenchyma. Relying on these data, patients
      should not be excluded from TESE based on serum FSH level, age, prior
      histopathologic pattern, or cytology/wet preparation results. These figures will
      allow clinicians to counsel patients with nonobstructive azoospermia
      informatively regarding TESE and their chances of having testicular sperm
      retrieved.

PMID- 9000193
TI  - Nonsurgical treatment of cavernosal venous leakage.
AB  - OBJECTIVES: To evaluate the results of treating patients with cavernosal venous
      leakage (CVL) with polyagent self-administered intracavernous pharmacotherapy and
      vacuum constriction devices (VCDs). METHODS: One hundred eighty-eight chronically
      impotent patients with a mean age of 58.8 years were studied. This group
      comprised 103 patients treated with standard-dose and high-dose polyagent self
      administered intracavernous pharmacotherapy and 85 patients treated with a VCD.
      The erectile response was related to the severity of CVL (mild, moderate, and
      severe). RESULTS: With standard polyagent pharmacotherapy, a response sufficient
      for satisfactory intercourse was achieved in 18 of 32 patients with mild CVL, 9
      of 54 patients with moderate CVL, and in 0 of 17 patients with severe CVL. With
      high-dose polyagent pharmacotherapy, a response sufficient for satisfactory
      intercourse was achieved in 22 of 32 patients with mild CVL, 29 of 54 patients
      with moderate CVL, and in 2 of 17 patients with severe CVL. With a VCD, a
      response sufficient for satisfactory intercourse was achieved in 23 of 30
      patients with mild CVL, 24 of 40 patients with moderate CVL, and in 10 of 15
      patients with severe CVL. CONCLUSIONS: CVL of mild to moderate severity can be
      treated with polyagent pharmacotherapy and VCDs with reasonable expectations of
      success. Severe CVL responds poorly to polyagent pharmacotherapy but can be
      treated with VCDs with reasonable results in motivated, adequately instructed
      patients.

PMID- 9000194
TI  - Early fluoroscopic realignment for traumatic urethral injuries.
AB  - OBJECTIVES: There are a variety of open surgical and endoscopic approaches to the
      treatment of traumatic urethral injuries. The objective of our study was to
      evaluate the efficacy of early fluoroscopic realignment of the urethra following
      traumatic injury. METHODS: Seven patients with urethral rupture injuries (two
      anterior and five posterior urethral injuries) were treated. Follow-up ranged
      from 1 to 35 months. RESULTS: Six patients had successful early realignment of
      the urethra and catheter placement. Two of these required no further treatment,
      whereas 3 required another procedure or procedures following catheter removal.
      One patient is presently being treated. In 1 patient, realignment was
      unsuccessful and subsequent open urethroplasty was required. CONCLUSIONS: Early
      fluoroscopic realignment appears to be a safe and effective method of treatment
      for severe traumatic urethral injuries.

PMID- 9000195
TI  - Smooth muscle development in the obstructed fetal bladder.
AB  - OBJECTIVES: To evaluate changes in the smooth muscle and connective tissue
      development in the obstructed and normal fetal bladder. METHODS: The smooth
      muscle and connective tissue composition of 19 fetal urinary bladders, including
      those of 9 fetuses with anatomic obstruction and 10 controls free of urologic
      disease, were analyzed by light microscopy and computer-assisted color image
      analysis. RESULTS: The bladder wall thickness was markedly increased in
      obstructed fetuses throughout gestation as compared with that in controls. The
      disparity in bladder wall thickness increased rapidly during gestation. The
      percent area density of smooth muscle and connective tissue as well as the ratio
      of smooth muscle to connective tissue remained the same in the obstructed and
      normal control fetal bladders. CONCLUSIONS: Although bladder outlet obstruction
      is associated with a marked increase in bladder wall thickness, the percent of
      smooth muscle and connective tissue comprising the mural histology remains
      relatively constant as compared with that of normal fetal controls. This study
      suggests that bladder outlet obstruction in the fetus is not associated with
      excess collagen deposition but rather with an increased amount of bladder with
      normal cellular content and a concomitant increase in smooth muscle development.

PMID- 9000196
TI  - Primary gonadotropin releasing hormone and adjunctive human chorionic
      gonadotropin treatment in cryptorchidism: a clinical trial.
AB  - OBJECTIVES: The effect of intranasal gonadotropin-releasing hormone (GnRH) and
      intramuscular human chorionic gonadotropin (hCG) in the treatment of
      cryptorchidism was investigated in 48 prepubertal boys. METHODS: Forty-eight
      prepubertal boys with 70 undescended testes were enrolled into a prospective
      study between November 1989 and November 1991. GnRH was applied as nasal spray at
      a dose of 1.2 mg/day for 4 weeks. The patients with partial descent were
      subsequently treated with 1500 IU hCG weekly for 3 weeks. RESULTS: Complete
      descent was observed in 53% (37 of 70) of testes; 58% (15 of 26) in unilateral
      and 50% (22 of 44) in bilateral undescended testes. One abdominally located
      testicle did not respond to therapy. Of 37 testes located in the inguinal canal,
      seven (19%) descended. On the other hand, descensus rates were 100% for the
      testes located at the external inguinal ring and at a high scrotal level. Six
      primarily descended testes (16%) showed relapse during the follow-up. Surgery was
      performed in 12 patients (14 testes), revealing associated hernia in nine testes
      and epididymal anomalies in four. CONCLUSIONS: We believe that the GnRH and hCG
      combination is an effective therapy for undescended testes located at and beyond
      the external inguinal ring and should be the first treatment choice because of
      its noninvasiveness. Both unilateral and bilateral undescended testes responded
      with similar success rate to hormonal therapy. Surgery should be considered for
      proximal cryptorchidism.

PMID- 9000197
TI  - New techniques for construction of efferent conduits based on the Mitrofanoff
      principle.
AB  - Presently, urinary diversion with continence mechanisms based on the Mitrofanoff
      principle is frequently used. For its construction, the critical issue is related
      to the choice of efferent conduit; the most widely used are the appendix and the
      tapered ileum. Here, we present two alternative techniques for construction of
      tubes applicable to the same function. Ten dogs underwent operations with two
      different types of tubes constructed through transversal tubularization of small
      segments of ileum. These tubes were implanted in the bladder. The dogs were
      followed up for 30 days, during which all were continent. Their tubes were easily
      catheterized. The techniques described met the criteria defined for an efferent
      tube to be used according to the Mitrofanoff principle.

PMID- 9000198
TI  - Acute cortical necrosis.

PMID- 9000200
TI  - Horseshoe kidney with a retrocaval ureter.
AB  - Horseshoe kidney and retrocaval ureter are two uncommon congenital anomalies of
      the genitourinary system that have rarely been reported to occur in the same
      patient. In each case previously reported, the isthmus of the horseshoe was
      positioned posterior to the inferior vena cava and anterior to the aorta. In no
      case was the diagnosis of both anomalies made preoperatively. We report a case of
      simultaneous horseshoe kidney and retrocaval ureter diagnosed by preoperative
      imaging studies and discuss the diagnostic evaluation and surgical management of
      this rare entity.

PMID- 9000201
TI  - The utility of video-assisted thoracic surgery in the diagnosis of pulmonary
      metastases from renal cell carcinoma.
AB  - The definitive diagnosis of pulmonary metastases requires histologic
      confirmation. Traditional methods of obtaining tissue for histologic review
      include transbronchial approaches, percutaneous transthoracic needle biopsy, and
      open lung biopsy. The purpose of this study is to identify the most effective
      methods of obtaining histologic confirmation of pulmonary metastases. The utility
      of video-assisted thoracic surgery in diagnosing pulmonary metastases is
      demonstrated in 2 patients with metastatic renal cell carcinoma. The diagnostic
      yields and complication rates of transbronchial approaches, percutaneous needle
      biopsy, open lung biopsy, and video-assisted thoracic surgery are compared.
      Finally, an algorithm for the evaluation of pulmonary lesions is presented.

PMID- 9000199
TI  - Nonseminomatous germ cell tumor of the testis.

PMID- 9000202
TI  - Perirenal myelolipoma.
AB  - Extra-adrenal myelolipomas are rare, benign tumors composed of hematopoietic and
      adipose elements. Although these tumors can cause local symptoms or hemorrhage,
      they are generally asymptomatic. However, when discovered intraoperatively, they
      pose a diagnostic dilemma to the urologic surgeon. We present a case of perirenal
      extra-adrenal myelolipoma discovered intraoperatively in a patient with von
      Hippel-Lindau disease undergoing partial nephrectomy.

PMID- 9000203
TI  - Laparoscopic pyelolithotomy.
AB  - Laparoscopic surgery has been applied to virtually every aspect of urinary tract
      disease. Presented is a case of laparoscopic-extended pyelolithotomy accomplished
      in a 16-month-old child with a large cystine stone that occupied the child's
      entire renal pelvis. Although not the first pyelolithotomy accomplished
      laparoscopically, we believe this to be the first extended laparoscopic
      pyelolithotomy and also believe this is the youngest patient in whom laparoscopic
      pyelolithotomy has been done. Extracorporeal shock wave lithotripsy and
      percutaneous and endoscopic stone techniques have drastically modified the
      management of urolithiasis. However, select cases in which these techniques may
      not be applicable (such as this toddler with bulky cystine lithiasis) may require
      open surgery. The laparoscopic approach represents an excellent, yet less
      invasive option.

PMID- 9000204
TI  - Desmoid tumor-ureteral fistula in Gardner's syndrome.
AB  - Gardner's syndrome (GS) is complicated by abdominal desmoid tumors in
      approximately 8% of cases. We describe two cases of ureteral obstruction and
      fistulization due to rapidly enlarging desmoid tumors. Initial management
      consisted of placement of ureteral stents to provide urine drainage from the
      kidney as well as from the collection in the cavities within the desmoid tumors.

PMID- 9000206
TI  - Primary lymphoma of the male urethra.
AB  - An elderly man presented with urinary outflow obstruction and a smooth mass
      arising from the bulbar urethra. Biopsy revealed large cell lymphoma, B cell
      subtype. A literature review revealed no previous cases of undisseminated
      lymphoma arising within the male urethra. The obstructing mass and symptoms
      resolved with multiagent chemotherapy.

PMID- 9000205
TI  - Anal tenesmus caused by seminal vesicle cyst.
AB  - Congenital cysts of the seminal vesicles with ipsilateral renal aplasia or
      dysplasia are rare but have been well described in the literature. We report the
      first case where anal tenesmus was the only presenting symptom. Another unique
      feature was the combination of this anomaly with a duplication of the inferior
      vena cava.

PMID- 9000207
TI  - Preservation of shock-wave-induced renal histologic changes by dermatan sulfate.
AB  - OBJECTIVES: To evaluate the protective effects of glycosaminoglycan (GAG)
      administration on shock-wave-induced renal histologic alterations, an
      experimental study using dermatan sulfate administration (DS) in rabbits was
      performed. METHODS: The study included 45 white New Zealand rabbits; 36 were
      divided into two groups before shock-wave application. Animals in the first group
      (n = 18) received no specific medication before or after shock-wave treatment;
      animals in the second group (n = 18) received subcutaneous DS administration for
      a period of 2 months, beginning 2 weeks before shock-wave application. Following
      different numbers of shock-wave application (500, 1000, or 1500 shock waves),
      histopathologic evaluation of treated kidneys was made under light microscopy
      after 24 hours and 3 months. Nine animals were used for the control group.
      RESULTS: During 24-hour examination, most of the kidneys in both groups
      demonstrated varying degrees of histopathologic alterations, depending on the
      number of shock waves applied. Among the most prominent pathologic features were
      protein deposition with free erythrocytes in the tubular lumen, glomerular
      hemorrhage, tubular dilation and degeneration, protein in Bowman's capsule,
      hyperemia, and mononuclear cell infiltration at the interstitial level. As
      opposed to the 24-hour evaluation findings, long-term (3-month) follow-up
      examination revealed histopathologic alterations that decreased but did not
      totally disappear in animals receiving no DS. Glomerular basement membrane
      thickening, mononuclear cell infiltration and limited protein deposition in some
      tubules, together with cortical interstitial fibrosis, were observed to some
      extent in these animals. On the other hand, no severe histopathologic alteration
      with normal glomerular basement membrane appearance was noted in animals
      receiving DS medication. CONCLUSIONS: Our results indicated a long-term favorable
      protective effect of DS administration on morphologic abnormalities in rabbits
      undergoing shock-wave treatment. Although tubular alterations persisted to some
      extent, mononuclear cell infiltration has been limited and the natural appearance
      of the basement membrane has been well preserved in most of the treated animals.

PMID- 9000208
TI  - Transforming growth factor beta as a clinical biomarker for prostate cancer.
AB  - OBJECTIVES: Tumor biomarkers to detect prostate cancer earlier may reduce
      prostate cancer deaths. Transforming growth factor-beta1 and -beta2 (TGF-beta1
      and -beta2) become overexpressed in prostate cancer and might be useful tumor
      markers of prostate cancer. METHODS: Plasma and urinary TGF-beta1 and plasma TGF
      beta2 levels were studied preoperatively in 74 consecutive patients who had
      prostate cancer and underwent radical prostatectomy and were compared with those
      of 29 similarly aged male control patients who had no clinical evidence of
      prostate cancer. RESULTS: Plasma TGF-beta1 levels were similar in both prostate
      cancer and control groups and did not correlate with serum prostate-specific
      antigen (PSA), clinical and pathologic stages, or Gleason grade. Urinary TGF
      beta1 levels, however, increased 3.5-fold in patients with prostate cancer
      relative to controls and tended to be higher with advancing clinical and
      pathologic stages. Plasma TGF-beta2 levels, like plasma TGF-beta1 levels, were
      similar for both the study and control groups, but when stratified by pathologic
      stage or Gleason grade, patients with prostate cancer with pathologic Stage T2a
      and Gleason grade of 3 or less had significantly increased plasma TGF-beta2
      levels as compared with either control patients or patients with prostate cancer
      with pathologic Stages T2b/T2c and T3/T4 or Gleason grade of 4 or more,
      suggesting that early prostate cancer may contribute to plasma TGF-beta2 levels.
      CONCLUSIONS: Unlike plasma TGF-beta1 levels, urinary TGF-beta1 and plasma TGF
      beta2 levels were higher in patients with prostate cancer and may be useful
      biomarkers of prostate cancer.

PMID- 9000209
TI  - Reaction of the paraventricular nucleus of the hypothalamus and the dorsal
      nucleus of the vagus of rats to change in the gravitational environment.

PMID- 9000210
TI  - Thalamocortical relationships in the brain of white rats in the postischemic
      period (a morphometric investigation of cyto- and synaptoarchitectonics).

PMID- 9000211
TI  - Transmission of information regarding the quantitative characteristics of an
      object in ants.
AB  - Results of laboratory experiments demonstrating that ants are capable of
      assessing the number of objects within the limits of several tens and transmit
      this information to other individuals are described. It has been demonstrated
      that ants may use these capacities for transmitting information regarding the
      coordinates of an object.

PMID- 9000212
TI  - Orienting reaction in invertebrates.
AB  - Changes in motor and vegetative indices in freshwater crayfish during sudden
      changes in the environmental situation are described. The results suggest that
      freshwater crayfish characterized by a sedentary lifestyle nevertheless
      constantly control the milieu in which they find themselves, by recording diverse
      changes in its parameters. Apparently the physiological nature of the reactions
      to "neutral" stimuli issuing from the milieu, is, in representatives of the
      higher invertebrates, very similar to that of the higher mammals, and may be
      described using the concepts of the orienting reflex and activity of an
      investigatory character which follows it. The question is posed in this context
      of the possibility of the appearance in this situation of emotional reactions of
      the animals investigated.

PMID- 9000213
TI  - Long-term changes in the efficiency of inhibitory transmission in the
      thalamocortical neuronal networks induced by microstimulation of the cortex.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) of the efficiency of
      inhibitory transmission between different elements of a network took place in
      neuronal networks consisting of AC and MGB cells, as a result of MS of the
      cortex. LTP of inhibition was an input-specific effect, since it could develop
      simultaneously with LTP of the efficiency of excitatory transmission to the same
      cell and do not lead to a decrease in its baseline frequency. LTP (LTD) of
      inhibition was observed simultaneously with an increase (decrease) in the
      frequency of baseline impulse activity of the inhibitory neuron or neuron which
      is presynaptic in relation to an inhibitory neuron; the efficiency of the
      synaptic effect of one inhibitory neuron on various postsynaptic cells could vary
      in different directions. The data obtained may suggest the participation of both
      pre- and postsynaptic mechanisms in the modification of the efficiency of
      inhibition.

PMID- 9000215
TI  - Study of the activity of head ganglion cells of larvae of the Drosophila ts
      mutant with altered capacity for learning and increased activational properties
      of calmodulin.
AB  - The mitotic activity of cells of the head neural ganglion of Drosophila larvae of
      two genetic lines, the agts 3-mutant line, which possesses increased calmodulin
      activational properties and altered capacity for learning, and the wild type CS
      line, serving as a control, was studied. The value of the mitotic index, as a
      ratio of the number of dividing cells to their total number, was assessed. The
      mitotic index was calculated following the exposure of the larvae to a
      temperature of 37 degrees C for 30 min, and without exposure, at a temperature
      which was standard for the maintenance of Drosophila ts-mutants, 22 degrees C. A
      higher mitotic index was observed at 22 degrees C in the agts 3 line as compared
      with the CS line. Exposure to a temperature of 37 degrees C led to a sharp
      decrease in mitotic activity in both the lines investigated. The increase in
      mitotic index at 22 degrees C in the agts 3 line was presumptively related to an
      increase in the activational properties of calmodulin, which is characteristic
      for this line. Following preliminary treatment of the neural ganglia by the
      calmodulin inhibitor, trifluoperazine, at a concentration of 10(-3) M for 30 min,
      the difference between the mitotic index of the mutant and the control line
      disappeared due to its approximately three-fold decrease in the agts 3 line; this
      confirmed the hypothesis advanced and suggested an important role of calmodulin
      in the regulation of the mitotic activity of cells of the general ganglion of
      Drosophila larvae.

PMID- 9000214
TI  - NO synthase and guanylate cyclase inhibitors block modulation of the plasticity
      of common snail cholinoreceptors by 15-hydroxy-eicosatetraenoic acid.
AB  - The probable role of two second messengers, nitrogen oxide (NO) and cyclic
      guanosine monophosphate (cGMP) in the short- and long-latency effects of the
      acyclic eicosanoid 15(S)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-HETE) on
      the plasticity of somatic cholinoreceptors of identified RPa3 and LPa3 neurons of
      Helix lucorum, was investigated using the two-electrode voltage clamp technique
      on the membrane. It was demonstrated that N omega-methyl-L-arginine (an inhibitor
      of NO synthase), LY-83,583 [sic], and the dye methylene blue (inhibitors of
      soluble guanylate cyclase), when applied extracellularly, disrupt the short- and
      long-latency modulatory influences of 15-HETE on the depression of the inward
      current induced by acetylcholine during its rhythmic application to the soma. The
      participation of NO and cGMP in the modulatory effects of 15-HETE on the
      plasticity of cholinoreceptors is hypothesized.

PMID- 9000217
TI  - Motivation and reinforcement in the systemic mechanisms of behavior: dynamic
      reinforcement engrams.
AB  - Materials are presented which suggest the interaction of motivation and
      reinforcement in the systemic organization of behavioral acts in individual brain
      neurons. It was demonstrated that immune mechanisms participate in the
      interaction of motivation and reinforcement. It is postulated that reinforcement
      during learning, by means of backward afferentation, forms molecular
      reinforcement engrams in the neuronal structures of the action outcome acceptor.
      The molecular reinforcement engrams are built by processes of the synthesis of
      DNA and protein molecules in ribosomes. These engrams, during the succeeding
      appearances of the corresponding needs, are activated by the dominant motivation
      and in anticipation direct animals toward the satisfaction of their initial
      needs.

PMID- 9000218
TI  - Capacity of birds for transitive inference: the solution of the Gillan test by
      corvids and pigeons.
AB  - A system of four to five differentiations forming a series, in which the
      magnitude of the reinforcement (R) of each succeeding color stimulus was greater
      than the preceding by one unit, was formed in pigeons (Columba livia L.) and
      crows (Corvus corone cornix L.). The number of units of the R that was associated
      with each of the stimuli increased successively from stimulus pair to stimulus
      pair from one up to four to five (1st series) and from five to ten (2nd series).
      After the development of the system of differentiations, the capacity of the
      birds to compare the magnitudes of R in given new combinations of stimuli and to
      choose the stimulus associated with the greater R (transitive inference) was
      tested. Given small Rs, the pigeons and crows solved the test equally
      successfully; in the case of large reinforcements, the pigeons began to make
      random choices, while in the crows the proportion of correct choices decreased.
      The proportion of appropriate solutions was greater when it was a greater
      absolute difference between the number of units of the R to be compared. The
      solution of the test employed by the birds is not proof of their capacity for
      transitive inference, since it can be explained by their capacity for unexpected
      comparison of the absolute values of the R associated with each of the stimuli.

PMID- 9000216
TI  - Investigation of the influence of a vasopressin analog on the efficiency of
      glutamatergic transmission in the hippocampus.

PMID- 9000219
TI  - Physiologic characterization of novel aggressotropic neuropeptides.
AB  - Experimental data of physiological activity of synthetic analogs of three novel
      neuropeptides isolated from the bovine brain are presented. The characteristics
      of the influence of the peptides on various forms of aggressivity of rats-
      intermale, predatory, and defense--with central and peripheral administration,
      are demonstrated. The influence of the peptides on other types of behavior--the
      consumption of food and water, fear, locomotor activity--associated with the
      formation of aggression is demonstrated. The modulatory effects of the peptides
      on the responses of identified neurons of molluscs to neuromediators, serotonin,
      dopamine, and glutamate, which participate in the neurochemical support of
      aggressive behavior of rats, are documented.

PMID- 9000220
TI  - Generalised and signal-specific long-term nociceptive sensitization in the common
      snail.
AB  - It was found in experiments carried out in common snails that applications of a
      concentrated solution of quinine (10%) to the animal's head lead to long-term
      (more than 24 h) facilitation of defense reactions. Facilitation of synaptic
      components of the responses to test stimulation, an increase in the excitability
      of the membrane, and its depolarization correspond to the behavioral
      manifestations of long-term sensitization in the command neurons of defense
      behavior. The degree of manifestation of the sensitization effects depends on the
      duration of its development. After a one-day development of sensitization,
      manifestations of signal-specific sensitization, including site-specific
      sensitization (more pronounced synaptic facilitation in the responses to test
      stimulation of the segment of the body which had been subjected to the
      sensitizing influence, as compared with facilitation of responses to stimulation
      of other points) and modality-specific sensitization (more pronounced
      facilitation of responses to test stimulation which coincides in modality with
      the sensitizing stimulus, by comparison with the degree of manifestation of
      responses to a test stimulation of a different sensory modality), predominate.
      After a three-day development, signs of generalized sensitization predominated in
      the command neurons: marked facilitation of responses in all synaptic inputs of
      the command neurons, an increase in excitability, and depolarization of the
      membrane.

PMID- 9000221
TI  - Formation of taste aversion and preference in protein synthesis inhibition in
      rats.
AB  - The investigation was devoted to the role of the synthesis of protein and peptide
      factors during the formation of chemosensory memory in rats. Two models of
      gustatory memorization were used: conditioned taste aversion (CTA), induced by
      the association of the taste of saccharine with a toxic injection of lithium
      chloride, and enhanced taste preference (ETP), induced by the influence of
      preliminary drinking of a saccharine solution on its repeat consumption. It was
      found that, under conditions of the inhibition of protein synthesis in the brain
      of 43% by cycloheximide and of 59% by 8-azaguanine, CTA does not form. ETP does
      not form under the influence of cycloheximide, but not [sic] of 8-azaguanine. A
      hypothesis was advanced regarding the participation of a varied spectrum of
      protein and peptide substances in the formation of taste aversion and preference.
      An influence of protein synthesis blockers on the process of retrieval of
      gustatory memory was not found.

PMID- 9000222
TI  - State of the peripheral nervous system in patients with hypothalamic
      insufficiency.
AB  - An investigation was carried out by non-invasive techniques of the state of the
      peripheral nervous system in patients with a constitutional-acquired form of
      hypothalamic insufficiency. Ten healthy individuals were included in the control
      group. The presence of subclinical parasympathetic vegetative insufficiency was
      identified by cardiovascular tests. It was more marked in patients with an early
      onset of the neuroendocrine disturbances and longer course of the disease. In the
      opinion of the authors, this suggests the constitutional-acquired character of
      the vegetative disturbances. In addition, a slowing of the speed of conduction
      through the sudomotor preganglionic sympathetic fibers in the upper and lower
      extremities and the predominance of these disturbances in the group of patients
      with pronounced dysraphic status were identified. The latter suggests a defect of
      the laying down of these peripheral vegetative fibers. This investigation makes
      it possible to hypothesize that subclinical peripheral insufficiency is one of
      the factors governing the occurrence of both permanent (tachycardia, elevations
      of AP, hyperhidrosis) and paroxysmal vegetative disturbances (panic attacks,
      migraine) in hypothalamic insufficiency.

PMID- 9000224
TI  - Genomic drift of Toxoplasma gondii.
AB  - We review herein studies concerning the genomic polymorphism of Toxoplasma gondii
      including 3 clones (1 linked with mouse pathogenicity), 5 zymodemes, and 13
      schizodemes. Because mutations occur with some frequency and several allelic
      configurations are present in isolates grown in the same environment, we conclude
      that many of the mutations may not be affected by selection pressure. However,
      the gametocyte-forming ability is under selection pressure from the hose and
      depends on the development of bradyzoites in tissue cysts. After prolonged
      multiplication exclusively in the tachyzoite stage in mice and, possibly, in
      patients the gametocyte-forming ability may be lost. To avoid this genomic
      change, isolates should be passed in the laboratory, permitting bradyzoite and
      tissue-cyst formation. Mouse pathogenicity is selected for during mouse passage.
      We find no major genomic instability justifying species or subspecies
      distinctions.

PMID- 9000223
TI  - Influence of aspirin on the contingent negative wave in healthy subjects.
AB  - A study was made of the alterations of the parameters of the slow brain
      potential, the contingent negative wave, under the influence of aspirin in
      healthy individuals, using the double blind method. The early and late wave of
      the CNW were investigated. A statistically significant decrease in the early CN
      wave was obtained after the ingestion of aspirin, and an increase in the late
      wave after the ingestion of aspirin and placebo. A central effect of aspirin,
      affecting the noradrenergic and dopaminergic brain systems, is hypothesized to
      explain the changes described.

PMID- 9000225
TI  - Use of a recombinant antigen, SAG2, expressed as a glutathione-S-transferase
      fusion protein to immunize mice against Toxoplasma gondii.
AB  - The capacity of Toxoplasma gondii surface protein SAG2 to induce protective
      immunity against the parasite in mice was studied using recombinant SAG2
      expressed as a glutathione-S-transferase (GST) fusion protein incorporated into
      immune stimulating complexes (iscoms). Immunization with the iscoms resulted in
      the production of antibodies recognizing SAG2 as well as GST. After oral
      challenge infection with T. gondii oocysts or tissue cysts, no protective effect
      was observed. On the contrary, mice immunized with fusion SAG2 or with GST iscoms
      died earlier than non-immunized control mice.

PMID- 9000226
TI  - Cytokine responses in mice infected with Angiostrongylus cantonensis.
AB  - For determination of the kinetics of cytokine production and its possible role in
      host resistance to Angiostrongylus cantonensis in the mouse, Th1 [interleukin 2
      (IL-2) and interferon gamma (IFN-gamma] and Th2 (IL-5 and IL-4) cytokine
      production in the cerebrospinal fluid (CSF), sera, and culture supernatants of
      spleen cells (SC) or cervical lymph-node cells (CLNC) of infected BALB/c and
      C57BL/6 mice was assessed by a sandwich enzyme-linked immunosorbent assay
      (ELISA). IL-5 and IL-4 were detected in CSF of both strains, with a peak response
      occurring at around days 12-15 and 20 postinfection (p.i.), respectively. A
      reverse transcriptase-polymerase chain reaction (RT-PCR) assay also revealed
      prominent IL-5 and IL-4 mRNA expression in T-cells but not in eosinophils in CSF.
      SC and CLNC stimulated with A. cantonensis young adult-worm antigen released IL-5
      in vitro at and after day 20 p.i. Contrarily, IFN-gamma production in CSF and SC
      or CLNC culture supernatants was almost negligible before day 30 p.i. IL-5, IL-4,
      and IL-2 production in culture supernatants was rather prominent in resistant
      C57BL/6 mice as opposed to susceptible BALB/c mice as assessed by the magnitude
      of increase over preinfection levels. Antigen-specific IgG1 (but not IgG2a)
      responses were more prominent in C57BL/6 mice than in BALB/c mice. These data
      suggest that systemic and local Th2 cytokine responses, especially those
      involving IL-5, are predominant in A. cantonensis-infected mice and that IL-5 is
      an important cytokine underlying the innate resistance of the mouse against A.
      cantonensis.

PMID- 9000227
TI  - Maintenance of the life cycle of Echinostoma trivolvis (Trematoda) in
      dexamethasone-treated ICR mice and laboratory-raised Helisoma trivolvis
      (Gastropoda).
AB  - Echinostoma trivolvis is a ubiquitous 37-collar-spined echinostome found in
      aquatic birds and mammals and in the planorbid snail Helisoma trivolvis. This
      echinostome has not been cycled continuously in the laboratory. The present
      report provides details on the continuous life cycle of E. trivolvis in
      dexamethasone-treated ICR mice and laboratory-raised H. trivolvis snails.
      Previous attempts to obtain patent adult of E. trivolvis in mice hosts failed
      because of worm injection within 2 weeks of infection. ICR mice infected with
      encysted metacercariae and injected with 2 mg/kg dexamethasone daily for 28 days
      yielded gravid worms that produced 250-500 eggs/worms at 21 and 28 days
      postinfection (p.i.). Miracidia derived from these eggs or eggs containing fully
      developed miracidia were capable of infecting 3- to 5-mm shell-diameter,
      laboratory-reared H. trivolvis snails. These snails released cercariae by 35 days
      p.i. Cercariae encysted in the kidney-pericardium of the snails. Encysted
      metacercariae could be excysted in vitro in an alkaline trypsin-bile salts medium
      or in vivo when fed to domestic chicks.

PMID- 9000228
TI  - Polymerase chain reaction-based construction of cDNA libraries from minute
      amounts of third-stage and fourth- and fifth-stage larvae of Dictyocaulus
      viviparus.
AB  - A strategy is described for the amplification and cloning of cDNA from minute
      amounts of Dictyocaulus viviparus larvae. Initially, third-stage larvae (L3) were
      used to establish the procedure. Amplification of cDNA synthesized from
      approximately 400 ng total RNA from 5,000 L3 generated products that were more
      than 800 bp in length. The unidirectional cloning of amplified cDNA products led
      to the construction of a UNI ZAP c DNA library with 1 x 10(6) clones. Screening
      with a homologous oligo(dT)-primed digoxigenin-labeled cDNA probe as well as
      sequencing of seven randomly picked clones confirmed the successful cloning of
      lung-worm cDNA. Subsequently, approximately 600 ng total RNA was isolated and
      polymerase chain reaction (PCR) products of up to 2,400 bp were amplitied from
      400 fourth- and fifth-stage larvae (L4/L5). Cloning of these products resulted in
      a L4/L5 cDNA library of D. viviparus consisting of 5 x 10(5) recombinant clones.
      In all, 11 clones were randomly picked and sequenced, all revealing typical
      mRNA/cDNA characteristics. Comparison of the predicted amino acid sequence of the
      5' end of clone DvL5/7 revealed 100% homology with the actin gene of several
      other helminths.

PMID- 9000229
TI  - Ultrastructure and cytochemistry study of Goussia sparis (Protozoa: Apicomplexa)
      stages from the intestine of the gilthead sea bream Sparus aurata L. (Pisces:
      Teleostei).
AB  - The ultrastructure and cytochemistry of merogonial and gamogonial stages and
      early unsporulated oocysts of Goussia sparis in the intestine of Sparus aurata
      were studied. The typical pellicle was observed in some stages. The different
      stages might appear in intraepithelial or supraepithelial positions, but they
      were always intracellular. First steps of two apparently different endomerogonies
      were observed in intra- and supraepithelial positions, respectively. An apparent
      ectomerogony also occurred in supraepithelial stages. Developing macrogamonts
      showed surface invaginations and were densely packed with ribosomes, well
      developed rough endoplasmic reticulum, mitochondria, amylopectin granules,
      lipidic droplets, and wall-forming-like bodies. The latter could participate in
      the formation of the oocyst wall. Abundant and large mitochondria, together with
      residual nuclei, appeared in advanced microgamonts. Microgametes showed two
      flagella with microtubul arranged according to the typical pattern. An increase
      in polysaccharide content was observed with coccidian development, reaching a
      maximum in zygotes and unsporulated oocysts.

PMID- 9000230
TI  - A case of human orotracheal myiasis caused by Wohlfahrtia magnifica.
AB  - A case of orotracheal myiasis in an 80-year-old man in coma for 1 week in the
      intensive care unit of Baskent University Hospital, Ankara, Turkey, is reported.
      A number of larvae of Wohlfahrtia magnifica were recovered repeatedly from the
      mouth and from the intubation tube of the patient and were reared to adults to
      facilitate identification. This case history points out the risky of myiasis
      caused by W. magnifica in the unconscious, debilitated patient.

PMID- 9000231
TI  - Schistosoma japonicum, S. mansoni, S. haematobium, S. intercalatum, and S.
      rodhaini: cysteine-class cathepsin activities in the vomitus of adult worms.
AB  - Vomitus from adults of five Schistosoma species was screened for biochemical
      homologues of the mammalian cysteine proteinases cathepsins B, H, and L. Bovine
      cathepsin B and rat cathepsin L served as references. Using the substrate Arg
      NMec, a schistosome cathepsin H-like activity was never detected. All species
      degraded the cathepsin B substrate Z-Arg-Arg-NMec, but distinct species
      differences were observed with respect to pH optima and buffer preferences. The
      cathepsin B and L substrate Z-Phe-Arg-NMec was similarly degraded by all species,
      and activity was abolished by the cysteine proteinase inhibitor E-64. Preferences
      by vomitus proteinase activities for Z-Phe-Arg-NMec over Z-Arg-Arg-NMec were
      similar to or higher than those found for bovine cathepsin B but well below those
      observed for rat cathepsin L; also, the preferential cathepsin L inhibitor Z-Phe
      PheCHN2 only partially inhibited proteinolytic activity. The results suggest the
      possible presence in vomitus of a minor cathepsin L-like activity and demonstrate
      a major cathepsin B-like activity that is biochemically variable between
      schistosome species.

PMID- 9000232
TI  - Eosinophil chemotactic factor release from neutrophils induced by stimulation
      with Schistosoma japonicum eggs.
AB  - The neutrophil is one of the sources of eosinophil chemotactic factor (ECF) in
      the presence of some stimulants. In the present study we showed that guinea-pig
      neutrophils could release ECF upon stimulation with Schistosoma japonicum eggs.
      ECF release from neutrophils began as early as 5 min after the stimulation and
      reached a peak at 20 min. When homogenate of the eggs was separated into a water
      soluble fraction as soluble egg antigen (SEA) and a water-insoluble fraction
      (eggshell), both preparations possessed a potent neutrophil-stimulating activity
      to release ECF. The ECF release was dependent on the concentration of eggshells
      or SEA or on the number of neutrophils. The neutrophil-stimulating activity of
      eggshells was stable to heat, HCl, or pronase treatment but sensitive to NaOH
      treatment. When the eggs or eggshells were washed with acetone or Tween-20, they
      lost the neutrophil-stimulating activity to release ECF, indicating that the
      neutrophil-stimulating factor (NSF) possesses a lipid nature. The molecular
      weight of NSF extracted from the eggshells was estimated to be about 1000 Da by
      gel chromatography on Sephadex G25. The possible role of eggshells in the
      formation of eosinophil-rich granulomatous lesions in schistosomiasis japonica is
      discussed.

PMID- 9000233
TI  - Proteolytic enzymes of infective larvae and adults of Trichostrongylus
      colubriformis and Haemonchus contortus.
AB  - The aim of this study was to acquire preliminary characterisation of the
      proteolytic enzymes of Trichostrongylus colubriformis and Haemonchus contortus so
      as to obtain a better understanding of the parasites' defence mechanisms against
      the host immune response. The proteinase band-pattern activity obtained using
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed nine
      bands in T. colubriformis and H. contortus L3 larvae and four bands in adult T.
      colubriformis at alkaline pH. Similar testing of adult H. contortus at acidic pH
      gave four bands. Within the same species the same proteinase may occur in both
      larvae and adults. Some enzymes of similar molecular weight occurred in both
      species, but their relative activities differed. The majority of proteinases of
      T. colubriformis and H. contortus larvae and adult forms are generally of high
      molecular weight (35-200 kDa). Because proteinase of T. colubriformis and H.
      contortus have been difficult to classify on the basis of their enzymatic
      activity, we suggest they may be proteasomes.

PMID- 9000234
TI  - Detection of circulating Trichinella spiralis larvae by polymerase chain
      reaction.
AB  - Several investigators have successfully applied the polymerase chain reaction to
      the amplification of DNA from Trichinella spiralis muscle-stage larvae. We show
      herein that specific DNA can be amplified from T. spiralis migratory larvae in
      the blood of experimentally infected mice. The polymerase chain reaction detected
      the presence of migratory larvae in mouse blood from day 5 to day 14 of
      infection. The technique may be applied to human trichinosis, but its diagnostic
      value will depend on the severity and stage of the infection.

PMID- 9000235
TI  - Schistosoma mansoni: unisexual infections sensitized mice for granuloma formation
      around intravenously injected eggs.
AB  - Mice carrying unisexual infection with male or female Schistosoma mansoni for 9
      weeks developed accelerated and augmented reactions to S. mansoni eggs injected
      intravenously. The size of circumoval granulomas observed in the lungs of
      unisexually infected mice did not differ significantly from the reactions seen in
      bisexually infected mice. Tissue eosinophilia in the granulomas was also
      augmented similarly over that in naive mice by unisexual or bisexual infection.
      The cross-reactivity between worm and egg antigens is relevant to the development
      of acute toxemic schistosomiasis mansoni and, perhaps, to the consideration of
      antigens to be used for vaccination against S. mansoni infection.

PMID- 9000236
TI  - Description of an improved method for Blastocystis hominis culture and
      axenization.
AB  - An improved method for Blastocystis hominis culture and axenization was developed
      in the present study. Stool samples were cultured in prereduced Boeck-Drbohlav
      NHI modified medium (with several modifications) supplemented with antibiotics
      (0.4% ampicillin, 0.1% streptomycin, 0.0006% amphotericin B). Axenization was
      performed by the combination of partial purification of B. hominis by Ficoll
      metrizoic acid gradient and inoculation in fresh medium containing active
      antibiotics against remaining bacteria. A total of 25 strains were obtained by
      this procedure. The time required for axenization ranged between 3 and 5 weeks.
      The generation time of axenic strains ranged from 6.6 to 12.1 h (mean +/- SD
      110.0 +/- 1.8 h) and the mean number of generations was 2.5 +/- 0.6 h per 24 h.
      The size of vacuolar and ameboid forms found in stools and in culture was
      similar. The special formulation of the medium used reduced the generation time
      and did not modify the cellular size as compared with fecal forms.

PMID- 9000237
TI  - Paramphistomum daubneyi: the development of redial generations in the snail
      Lymnaea truncatula.
AB  - Rediae of Paramphistomum daubneyi were counted and measured in Lymnaea truncatula
      to elucidate the variability in the numbers of free rediae and cercariae
      occurring between naturally infected snails and experimental single-miracidium
      infections. Experiments were performed using one miracidium per snail and snail
      raising was carried out at 20 degrees C. Two redial generations succeeded each
      other in the snail until day 49. A mean of 8-10 rediae differentiated in the
      sporocyst at days 7 and 14; the remaining germ balls and redial embryos decreased
      in number after day 21. First-generation rediae became free in the snail's body
      starting at day 14 and their number increased to a mean of 7.5 at day 49, with a
      maximum of 10 rediae being detected in 1 snail. They produced second-generation
      rediae, which exited from the body starting at day 28, and then cercariae, which
      exited from day 42 onward. The count of second-generation rediae was 6-6.2/snail
      at day 49, with a maximum of 12 being detected in 1 snail; they produced only
      cercariae.

PMID- 9000238
TI  - Chaetotaxy and armature of Ichthyocotylurus erraticus (Rudolphi, 1809) and I.
      variegatus (Creplin, 1825) cercariae (Digenea, Strigeidae).
AB  - The armature and chaetotaxy of Ichthyocotylurus erraticus (Rudolphi 1809) and I.
      variegatus (Creplin 1825) cercariae were studied using scanning electron
      microscopy (SEM) and silver staining of the argentophilic sensilla. This
      represents the first detailed investigation of the surface structures of
      cercariae belonging to this genus. Both species exhibited a similar armature,
      although differences were recorded in the number of spines comprising the pre
      oral tuft and the number of rows of spines in the post-oral collar. The number
      and the distribution of sensilla were found to be identical for both species of
      cercariae. Four types of sensilla, common to both species, were identified that
      differed in cilia length and in the structure of the surrounding collar. The
      distribution of particular sensillary forms was found to be consistent in both
      species.

PMID- 9000239
TI  - Ultrastructural features of the female reproductive system and female gametes of
      Nectonema munidae Brinkmann 1930 (Nematomorpha).
AB  - Two stages of late juvenile females of Nectonema munidae Brinkmann, 1930 are
      described in terms of their productive system. In the first stage the body is
      filled with a tissue called the gono-parenchyme. Spherical compartments are
      separated into a central cavity. IN the second stage the body surrounds a large
      primary body cavity that contains a large quantity of oocytes and scattered nurse
      cells. Different types of vesicles occur in these structures. The present results
      are compared with the features known for the female reproductive system of
      species of Gordiida, the sister taxon of Nectonema within the Nematomorpha.

PMID- 9000240
TI  - Identification of Haemonchus species in domestic ruminants based on morphometrics
      of spicules.
AB  - An easy and rapid tool for the individual identification of Haemonchus species in
      domestic ruminants might be very useful in the study of natural populations,
      especially when two (or three) species are sympatric. Techniques based on
      cytology, cuticular-ridge patterns, sublateral hypodermic chords, or molecular
      biology allow species identification but are either expensive or time-consuming.
      Therefore, a discriminant function combining three measures of male spicules was
      established from experimental infections with H. contortus in both sheep and
      goats and with H. placei in zebu. The discriminant function was evaluated on
      individual worms and on average values obtained in natural and experimental
      populations throughout the world. It was compared with a previously established
      function. The use of our function permitted better species identification for all
      Haemonchus species of ruminants, including H. longistipes from camels and H.
      similis from cattle.

PMID- 9000241
TI  - Construction and rapid screening of a representative yeast artificial chromosome
      library from the Plasmodium falciparum strain Dd2.
AB  - Large genomic DNA fragments from the Plasmodium falciparum clone Dd2 have been
      cloned as artificial chromosomes in yeast (YAC). The resulting library has a 10
      fold redundancy for single-copy genes and consists of 1440 individual clones,
      including 240 telomeric clones, with an average insert size of 150 kb. A novel
      hybridization method was developed for the rapid and cost-effective screening of
      protozoan YAC libraries. The Dd2 YAC clones will facilitate a positional approach
      to the parasite's genes and aid in the dissection of genetic loci associated with
      the virulence and pathogenicity of P. falciparum.

PMID- 9000242
TI  - The immunodiagnostic potential of Echinococcus granulosus adult-worm antigens in
      human cystic echinococcosis.
AB  - Echinococcus granulosus adult-worm antigens were characterised for assessment of
      their immunodiagnostic potential for human cystic echinococcosis (CE). The
      analysis of worm extracts by enzyme-linked immunosorbent assay (ELISA) showed a
      sensitivity of 83% for CE, which is comparable with data obtained for cyst-fluid
      based serodiagnostic tests. Immunoprecipitation of in vitro-translated E.
      granulosus worm mRNA revealed a range of low-molecular-weight antigenic proteins
      (12-45 kDa) recognised by human CE sera. E. granulosus adult worms may provide an
      additional or alternative source to metacestode material for the isolation of
      both native and recombinant antigens to be considered for the serodiagnosis of
      human echinococcosis.

PMID- 9000243
TI  - Some ultrastructural aspects of Henneguya striolata sp. nov. (Myxozoa,
      Myxosporea), a parasite of the Amazonian fish Serrasalmus striolatus.

PMID- 9000244
TI  - Identification of Entamoeba histolytica and E. dispar cysts in stool by
      polymerase chain reaction.
AB  - An attempt to identify cysts of Entamoeba histolytica and E. dispar in human
      stool was conducted by polymerase chain reaction (PCR) using two sets of primers
      (p11 plus p12 and p13 plus p14) specific for either species of ameba. The cysts
      in stool specimens obtained from 12 infected individuals were concentrated,
      freeze-thawed, and treated with Triton X-100 before their examination by PCR. The
      results of PCR on the cysts were generally consistent with data obtained by PCR
      on ameba trophozoites hatched from the cysts, by zymodeme analysis, and by enzyme
      linked immunosorbent assay (ELISA) and with clinical findings. This PCR was
      negative for the stool containing large numbers of cysts of either E. coli, E.
      hartmanni, or Giardia lamblia as well as for the stool specimens obtained from
      uninfected individuals. The ameba cyst in stool processed using the present
      method was effective for the PCR analysis even after 1 month of storage at 4
      degrees C. The present PCR was sensitive enough to detect ten cysts of either of
      the amebae.

PMID- 9000245
TI  - Expression of a 70-kDa heat-shock-related protein during transformation from free
      living infective larvae to the parasitic stage in Strongyloides venezuelensis.
AB  - The in vitro transformation system of Strongyloides venezuelensis has been
      established which induces free-living infective larvae to transform into the
      parasitic stage by a temperature shift from 25 to 37 degrees C. Comparison of the
      profiles of proteins labeled with [35S]-methionine in infective larvae at 25 and
      37 degrees C with marked morphological transformation revealed an increase in the
      70-kDa protein, thus showing these proteins to be related to the family of heat
      shock proteins. In addition, the new appearance of two complexes between 16-kDa
      and 22-kDa proteins was observed. The 70-kDa protein cross-reacted with
      monoclonal antibody against human heat-shock protein 70, which was constitutively
      expressed. These proteins, synthesized during the transformation of S.
      venezuelensis from the infective larval stage to the parasitic stage, might be
      crucial for biochemical events that regulate the infectivity of the parasite for
      the host.

PMID- 9000246
TI  - Improvements to the TMSBr method of peptide resin deprotection and cleavage:
      application to large peptides.
AB  - The original trimethylsilyl bromide (TMSBr) method of peptide resin deprotection
      and cleavage has been modified for convenience and applicability to larger
      peptides. Equal amounts of a 66-residue test peptide resin were cleaved by the
      standard hydrogen fluoride (HF) procedure, the original TMSBr method and the
      modified TMSBr method. The peptide profile from the original TMSBr cleavage
      procedure showed multiple products and a lower overall yield. In contrast, the
      modified TMSBr procedure gave high yields of crude products comparable in purity
      to those obtained by HF cleavage.

PMID- 9000247
TI  - Intramolecular pyrophosphate formation during N alpha-9
      fluorenylmethyloxycarbonyl (Fmoc) solid-phase synthesis of peptides containing
      adjacent phosphotyrosine residues.
AB  - The derivative N alpha-9-fluorenylmethyloxycarbonyl-O-phospho-L-tyrosine [Fmoc
      Tyr(PO3H2)-OH] has been used successfully for the solid-phase synthesis of a wide
      variety of phosphorylated peptides. However, when it is used to incorporate
      consecutive phosphotyrosine residues, a pyrophosphate linkage can form between
      the two adjacent tyrosines. Incorporation of unprotected phosphotyrosine during
      the synthesis of peptides with multiple phosphotyrosine residues has been studied
      as a function of coupling conditions and the absence or presence of intervening
      amino acid residues. The pyrophosphate-forming side reaction is more severe with
      increased coupling times and/or repetitions of coupling and occurs only when the
      phosphotyrosine residues are directly adjacent to one another.

PMID- 9000248
TI  - Assessing delivery of lipopeptides into the cytoplasm of intact cells by a
      functional assay based on PKC inhibition. I. The Jurkat model.
AB  - We have developed a functional assay to verify the delivery into the cytoplasm of
      a 14-amino acid hydrophilic peptide, modified by the incorporation of a palmitoyl
      lysine residue into the N- or C-terminal end. This assay is based on the use of a
      pseudo-substrate sequence for the protein kinase C (PKC) isoenzymes of alpha and
      beta for the quantification of PKC-mediated tumor necrosis factor (TNF) secretion
      after T-cell activation by phorbol ester and anti-CD3 MAb. This cellular assay is
      simple, and it allows for a rapid and comparative study of several peptides. The
      lipidic analogues of the pseudo-substrate peptide were able to inhibit TNF
      secretion in intact-activated Jurkat cells, with an EC50 in the 40-60 microM
      range, whereas the unmodified peptide was not active. Two control lipopeptides
      were also inactive, demonstrating that the palmitoyl-lysine group had no effect
      by itself. This study confirms that the modification of a relatively long peptide
      by the insertion of a palmitoyl-lysine into the N- or C-terminal end is
      sufficient to allow entry into intact cells.

PMID- 9000249
TI  - Antibody recognition of peptide sequences from the cell-cell adhesion proteins: N
      and E-cadherins.
AB  - Intercellular junctions present a formidable challenge for the paracellular
      delivery of drugs. Cadherins are calcium-dependent cell-cell adhesion molecules,
      which are responsible for the formation and regulation of these junctions. Anti-E
      cadherin monoclonal antibody can bind to E-cadherin (uvomorulin) and inhibit cell
      cell adhesion through the inhibition of cadherin-cadherin interactions. The
      objective of this study was to utilize this monoclonal anti-E-cadherin antibody
      to map the extracellular domains of E- and N-cadherin. This was accomplished by
      using two different enzyme-linked immunosorbent assays (ELISAs), a regular
      indirect ELISA and an immobilized-peptide ELISA. Two peptides from each
      extracellular domain were recognized by this anti-E-cadherin antibody. By mapping
      the extracellular domains of cadherins, peptides that have discrete roles in cell
      cell adhesion can be identified. This will aid in the design of synthetic
      peptides that can modulate intercellular junctions to improve drug delivery.

PMID- 9000250
TI  - Use of sequential oligopeptide carriers (SOCn) in the design of potent Leishmania
      gp63 immunogenic peptides.
AB  - The antigenic sequence Ac-IASRYDQL (gp63-SRYD) of the major surface glycoprotein
      of Leishmania, gp63, was covalently attached to the Lys-N epsilon H2 groups of a
      new sequential oligopeptide carrier (SOCn), namely, (Lys-Aib-Gly)n (n = 5.6), in
      order to obtain potent immunogens and site-specific antibodies. It was shown,
      using 1H-NMR spectroscopy, that the gp63-SRYD octapeptides bound to the SOCn
      retain their original structural profile outlined by an ionic interaction between
      R and D side chains and a type 1 beta-turn involving the QNH-->RCO hydrogen
      bonding. Also, the gp63-SRYD octapeptides linked to the carrier do not experience
      conformational restrictions, probably because of the favorable conformation of
      the SOCn. Immunizations of outbred rabbits with the peptide carriers designed
      resulted in high-titered antibody response to the gp63-SRYD octapeptide and the
      gp63 cognate protein. Thus, this chemically defined model may be used for
      incorporating "protective" Leishmania epitopes and ultimately for the design of a
      multivalent synthetic vaccine against leishmaniosis.

PMID- 9000251
TI  - Substitution of peptide bond 53-54 of HEL(52-61) with an ethylene bond rather
      than reduced peptide bond is tolerated by an MHC-II restricted T cell.
AB  - To probe the interactions between major histocompatibility class-II molecules and
      the amide bonds of the antigenic peptide main chain, we synthesized ethylenic and
      reduced analogues of HEL(52-61), an immunogenic peptide for murine major
      histocompatibility class-II IA k restricted T-cell clones. The synthesis of the
      corresponding ethylenic analogue of HEL(52-61) in position 53-54 was performed by
      coupling the Fmoc-protected tripeptide Asp-Tyr-psi [E, CH = CH]Gly with HEL(55
      61). Biological tests showed that the ethylenic peptide was presented by major
      histocompatibility class-II IA kappa molecule and recognized by HEL(52-61)
      specific T-cell clones. The corresponding reduced peptide of HEL(52-61) at
      position 53-54 neither stimulated T-cell clones nor competed with the natural
      peptide. These results show that, while reduced pseudopeptides might not be
      appropriate, ethylenic pseudopeptides may be used as probes to dissect the role
      of hydrogen bonding between the peptide main chain and MHC residues and also help
      in the design of more stable immunogenic peptides.

PMID- 9000252
TI  - Effects of intermittent and continuous subchronic administration of raclopride on
      motor activity, dopamine turnover and receptor occupancy in the rat.
AB  - With the purpose of finding means to circumvent the marked pharmacokinetic
      differences of raclopride between rats and man, the effects of intermittent and
      continuous administration of raclopride were compared in rats. Intermittent
      administration of raclopride via subcutaneous injections resulted in a prompt
      increase of dopamine (DA) turnover and decrease of motor activity but these
      effects were of short duration, probably due to rapidly decreasing raclopride DA
      D2 receptor occupancy. In contrast, but similar to schizophrenic patients on
      raclopride treatment, stable plasma raclopride levels and a steady DA D2 receptor
      occupancy above 70% were produced in the caudate-putamen and nucleus
      accumbens/olfactory tubercle, when raclopride was administered continuously via
      minipumps at daily doses above 2 mg/kg. Tolerance to the acute effects of
      raclopride on DA turnover and locomotion was found with both routes of
      administration but it was more marked with continuous administration. At
      continuous raclopride administration, tolerance to the effects of raclopride on
      DA turnover and spontaneous motor activity as well as supersensitivity to
      amphetamine-induced motor activity occurred when 70% or more of DA D2 receptor
      sites were occupied, i.e. the same degree of receptor occupancy as found in
      patients given therapeutic doses of raclopride.

PMID- 9000253
TI  - Alpha(1)- and beta-adrenoceptor-mediated increase in 86Rb(+)-uptake in isolated
      cardiomyocytes from adult rat heart: evidence for interaction between the two
      receptor systems.
AB  - The aim of the present investigation was to study the effect of alpha(1)- and
      beta-adrenoceptor stimulation, alone and in combination, on potassium uptake in
      isolated ventricular cardiomyocytes from adult rat heart, using the potassium
      analogue 86Rb+. The reliability of 86Rb+ as a potassium analogue was also
      investigated. Alpha(1)-, beta-, And combined adrenoceptor stimulation was
      achieved by using noradrenaline in the presence and absence of appropriate
      adrenoceptor antagonists. The uptake of 86Rb+ was found to increase linearly with
      time up to 20 min., both during basal and receptor-stimulated conditions. The
      basal uptake rate was about 0.18 ml/g protein x min. At 15 min. both alpha(1)-,
      beta- and combined adrenoceptor stimulation dose-dependently increased the
      86Rb(+)-uptake with a -logEC50 of 7.05, 6.68 and 6.73, respectively. The maximal
      increase in these series achieved by 5 x 10(-5) mol/l noradrenaline was 29%, 24%
      and 41% above basal level, respectively. Comparison of the maximal effects in the
      same cell preparations, with the observed value for combined adrenoceptor
      stimulation in each experiment as 100%, gave a relative maximal increase in
      86Rb(+)-uptake after separate alpha(1)-adrenoceptor stimulation of 67 +/- 8%, and
      of 68 +/- 6% after separate beta-adrenoceptor stimulation. The theoretically
      calculated value for combined adrenoceptor stimulation, if additivity, was 135 +/
      11%, which was significantly higher than the observed value (100%) (P = 0.026).
      The effect of noradrenaline was not limited by the maximal 86Rb(+)-uptake
      capacity, as 10(-5) mol/l forskolin increased the 86Rb(+)-uptake more than
      noradrenaline. Examining the reliability of 86Rb+ as potassium-analogue by
      combining 42K+ and 86Rb+ in the same experiments, showed that combined
      adrenoceptor stimulation dose-dependently increased both the 42K(+)- and 86Rb(+)
      uptake with the same potency and to the same extent. Thus 86Rb+ is a reliable
      potassium-analogue for these effects. In conclusion both alpha(1)- and beta
      adrenoceptor stimulation dose-dependently increased the cellular 86Rb(+)-uptake
      to the same extent and with the same potency. The observed maximal 86Rb(+)-uptake
      after combined adrenoceptor stimulation was significantly higher than the maximal
      effect after either form of separate receptor stimulation, but significantly
      lower than expected if the effects were purely additive. The results thus show
      inhibitory interaction between the two receptor systems.

PMID- 9000255
TI  - Does ibuprofen affect bilirubin-albumin binding in newborn infant serum?
AB  - Intravenous ibuprofen is being studied in sick, premature infants for the
      prevention of intraventricular haemorrhage and closure of the ductus arteriosus.
      We tested the effect of ibuprofen on bilirubin-albumin binding in adult and
      newborn infant serum by measuring the free ibuprofen concentration in the
      presence of bilirubin (reverse displacement method). At clinically appropriate
      ibuprofen concentrations the free fraction of bilirubin is increased by a factor
      of 4. Ibuprofen may increase the risk of bilirubin encephalopathy when used in
      sick, premature infants.

PMID- 9000254
TI  - Effect of arsenic (V) on the antioxidant defense system: in vitro oxidation of
      rat plasma lipoprotein.
AB  - Adult male rats were treated orally with sodium arsenate (10 mg As/kd/day) for 2
      days, and in increase in hepatic glutathione level was seen. Ascorbic acid
      content increased in both liver and plasma of intoxicated animals. Hepatic
      activities of superoxide dismutase and glutathione peroxidase did not change with
      the treatment and there was no increase in the level of lipid peroxidation
      measured as thiobarbituric acid-reacting substances (TBARS). Arsenic decreased
      the plasma level of uric acid and increased the plasma triglycerides content
      without modifying vitamin E levels. Both total lipoproteins and very low density
      lipoprotein plus low density lipoprotein (VLDL + LDL) fractions demonstrated
      greater propensity for in vitro oxidation than the corresponding untreated rats.
      The last finding might be a useful parameter for determining the degree of
      oxidative stress in the initial steps of intoxication with arsenic.

PMID- 9000256
TI  - In vitro effect of avarone and avarol, a quinone/hydroquinone couple of marine
      origin, on platelet aggregation.
AB  - We investigated the effect on human platelet aggregation of the naturally
      occurring quinone/hydroquinone couple, avarone and avarol. Avarone exerted
      antiplatelet activity both on platelet-rich plasma and, to a greater extent, on
      washed platelets. The quinone inhibited the platelet aggregatory process with all
      the agonists used. The highest inhibitory potency occurred with arachidonic acid
      or A23187 as stimulating agents. In the case of agonists such as adenosine 5'
      diphosphate, platelet-activating factor or U46619, the antiaggregatory effect was
      more pronounced on the second wave. Inhibition of the aggregatory process
      paralleled thromboxane B2 formation. Avarol also exerted antiplatelet activity,
      even though its inhibitory potency was much lower than that of avarone.

PMID- 9000257
TI  - Pharmacological analysis of local anaesthetic tolycaine-induced convulsions by
      modification of monoamines in rat brain.
AB  - The effects of a local anaesthetic, tolycaine, on brain monoamine levels were
      investigated during the convulsive process in rats. The influence of central
      monoamine modifications on tolycaine-induced convulsions was also examined.
      Tolycaine (140 mg/kg, intraperitoneally) produced a significant elevation of
      noradrenaline and 5-hydroxytryptamine levels in all brain regions in the
      convulsive state from the levels in the non-convulsive state. Their levels
      returned to normal during the postconvulsive state. Dopamine levels were depleted
      in the cerebral cortex, the striatum, and the ponsmedulla oblongata during the
      convulsive process and increased in the cerebellum. Pretreatment with alpha
      methyl-p-tyrosine, which depletes brain catecholamine, suppresses the tolycaine
      induced convulsions, as shown by a decrease in the incidence; L-3,4
      dihydroxyphenylalanine and bis-(1-methyl-4-homopiperazinyl-thiocarbonyl)
      disulfide, which increase brain catecholamine, intensified the convulsions, as
      shown by shortening of the latency and increase in the mortality. Antagonists of
      beta-adrenergic and dopamine receptors, such as propranolol, chlorpromazine and
      pimozide, markedly suppressed the convulsions, but an antagonist of alpha
      adrenergic receptor, phenoxybenzamine, had no effect. Furthermore, 5
      hydroxytryptophan, which increases brain 5-hydroxytryptamine, suppressed the
      convulsions, and DL-p-chlorophenylalanine, which depletes brain 5
      hydroxytryptamine, intensified them. Antagonists of 5-hydroxytryptamine receptor,
      methysergide and methiothepin, suppressed the convulsions. These results suggest
      that brain noradrenaline and 5-hydroxytryptamine are major regulators in the
      tolycaine-induced convulsive process and that central catecholaminergic neurones
      act in a stimulatory way on the tolycaine-induced convulsions, while serotonergic
      neurones act suppressively.

PMID- 9000258
TI  - Effects of calcium blockers on the cytosolic calcium, H2O2 production and
      elastase release in human neutrophils.
AB  - Activated neutrophils are assumed to be one plausible cause of tissue injury in
      the ischaemic and reperfused myocardium. We studied the inhibitory effects of the
      calcium antagonists felodipine, nimodipine and verapamil on human neutrophil
      activation in order to elucidate the mechanisms underlying their
      myocardioprotective effects and to determine whether calcium antagonists with
      different chemical structures vary in their effect on neutrophil activation.
      Neutrophils were stimulated with formyl-Met-Leu-Phe (0.1 microM) or by phorbol
      myristate acetate (0.16 microM), and the rise in cytosolic calcium and the H2O2
      production were determined. For felodipine, the inhibitory effect on granulocyte
      elastase release was also studied. The calcium antagonists reduced formyl-Met-Leu
      Phe and phorbol myristate acetate-induced neutrophil activation in a
      concentration-dependent manner, the order of potency being: felodipine >
      nimodipine > verapamil. For felodipine, the IC50 (concentration causing 50%
      reduction) values were 3 x 10(-6) and 2 x 10(-6) M for the formyl-Met-Leu-Phe
      induced cytosolic calcium increase and H2O2 production, respectively. The IC50
      value for the phorbol myristate acetate-induced cytosolic calcium increase was 6
      x 10(-6) and for H2O2 production 4 x 10(-6) M. For formyl-Met-Leu-Phe-induced
      granulocyte elastase release, the IC50-value was 5 x 10(-6) M. The inhibitory
      effect of felodipine on the phorbol myristate acetate-induced granulocyte
      elastase release did not exceed 50%. Nimodipine was a less potent inhibitor than
      felodipine for both formyl-Met-Leu-Phe- and phorbol myristate acetate-induced
      cell activities. Verapamil was even less potent than the other two agents. The
      present study demonstrates that felodipine potentially suppresses neutrophil
      activation at micromolar concentrations. However, this observation should not be
      directly extrapolated to explain the tissue protection by the compounds without
      evidence of profound local accumulation.

PMID- 9000259
TI  - Hypotensive and vasorelaxing activities of a lectin from the edible mushroom
      Tricholoma mongolicum.
AB  - A lectin, which exerted a hypotensive action in rats after intravenous injection
      via the jugular vein, was isolated from the mycelia of the edible mushroom
      Tricholoma mongolicum. The lectin possessed a molecular weight of 37 K and its
      hypotensive activity was dose-dependent. Administration of the lectin at a dose
      of 10 mg/kg body weight caused a mean arterial blood pressure reduction of 95.3
      +/- 7.4 mmHg. The lectin's hypotensive action was not mediated via autonomic
      ganglion transmission, alpha-adrenoceptors, beta-adrenoceptors, cholinergic
      receptors, histaminergic receptors, nor the renin-angiotensin system, but it was
      probably mediated through vasorelaxation via adenosine A2 receptors and/or nitric
      oxide production.

PMID- 9000260
TI  - Effect of cholecystokinin-B/gastrin receptor blockade on gastric acid secretion
      in conscious rats.
AB  - Gastrin, histamine and acetylcholine are physiological stimuli of gastric acid
      secretion. The cholecystokinin-B/gastrin receptor antagonists YM022 and RP73870
      were used to study the effect of gastrin receptor blockade on acid secretion.
      Gastrin, histamine, insulin or bethanechol were administered to conscious gastric
      fistula rats with or without the concomitant intravenous infusion of YM022 or
      RP73870. Other rats were subjected to pylorus ligation. YM022 and RP73870
      inhibited the gastrin-induced acid secretion in a dose- and time-dependent
      manner; maximal inhibition was observed at a dose of 0.3 mumol.kg-1.hr-1 for both
      YM022 and RP73870, the ID50 values being 0.02 mumol.kg-1.hr-1 and 0.05 mumol.kg
      1.hr-1 for YM022 and RP7870, respectively. At a dose of 0.3 mumol.kg-1.hr-1 YM022
      and RP73870 failed to inhibit basal and histamine-, bethanechol-, and insulin
      evoked secretion. They also failed to affect the secretion evoked by infusion of
      a cocktail of maximally effective doses of gastrin-17, histamine and bethanechol.
      YM022 and RP73870, finally, were without effect on the acid response to pylorus
      ligation. We suggest that endogenous gastrin in the conscious rat does not
      contribute to the basal acid secretion and does not participate in the acid
      response to histamine or to vagus stimulation.

PMID- 9000261
TI  - Progesterone modulation of diazepam withdrawal syndrome in mice.
AB  - The influence of progesterone and oestrogens on the benzodiazepine withdrawal
      syndrome in mice was studied. The intraperitoneal administration of 15 mg/kg of
      flumazenil induced a withdrawal syndrome in chronic diazepam-treated mice,
      characterized by jerks, usually accompanied by tail lifts, and seizures. The
      principal finding of the present work is that the intensity of diazepam
      withdrawal syndrome was significantly reduced by acute administration of
      progesterone as revealed by a low incidence of jerks and seizures. The action of
      progesterone could be due to a modulatory role of the hormone on neuronal
      activity as an anxiolytic agent. The modulatory activity of progesterone appears
      to be related to changes in the pharmacological properties of benzodiazepine
      receptors.

PMID- 9000262
TI  - Nitrofurantoin-induced hepatic and pulmonary biochemical changes in mice fed
      different vitamin E doses.
AB  - The hepatic and pulmonary effects of nitrofurantoin (40 mg/kg, intraperitoneally)
      were determined at 4 and 24 hr following its administration in mice fed for 10
      weeks with a vitamin E sufficient, deficient or enriched diet. Liver glutathione
      (GSH) was reduced by nitrofurantoin at 4 hr but was unchanged 20 hr later.
      Nitrofurantoin did not affect liver glutathione peroxidase, glutathione reductase
      or superoxide dismutase activities. Liver catalase activities were decreased by
      nitrofurantoin at 4 hr. Lung GSH levels were increased whilst glutathione
      peroxidase activity was decreased at 4 and 24 hr. Lung glutathione reductase
      activity was reduced in certain groups. Nitrofurantoin did not affect lung
      superoxide dismutase, but catalase was decreased at 24 hr. Liver malondialdehyde
      levels were increased by nitrofurantoin in the vitamin E deficient group whilst
      lung malondialdehyde levels remained unchanged. Both liver and lung
      malondialdehyde levels were unaffected by vitamin E supplementation when compared
      to the vitamin E-sufficient group. These results suggest that nitrofurantoin (40
      mg/kg) was deleterious to the liver and lung. Nitrofurantoin-induced lipid
      peroxidation was seen in vitamin E deficiency but an increase in dietary vitamin
      E content did not provide additional protection compared to the recommended daily
      allowance. The antioxidant activities of alpha-tocopherol and gamma-enriched
      tocotrienol were similar.

PMID- 9000263
TI  - Effects of benzopsoralen derivatives on HL60 and HeLa cells.
AB  - The effect of 4-hydroxymethyl-6,7,8,9-tetrahydro-2H-benzofuro-[3,2-g]-1-benzo
      piran-2-one (compound 1) and 4-hydroxymethyl-2H-benzofuro-[3,2g]-1-benzopiran-2
      one (compound 2), two new benzopsoralen derivatives, was tested on HL60 and HeLa
      cell lines in the dark and by UVA irradiation; 8-methoxypsoralen was used as a
      reference compound. The action of the compounds was evaluated by means of the
      neutral red uptake assay, by means of ultrastructure, morphometry and interaction
      with human erythrocytes membrane. In both HL60 and HeLa cell lines benzopsoralen
      derivatives showed more antiproliferative activity after UVA irradiation, however
      less than 8-methoxypsoralen. Compound 1 was more effective than compound 2 both
      in the dark and after UVA irradiation. The ultrastructure showed a morphological
      rank damage caused by these compounds: compound 2 induced slight modifications in
      the cytoplasm organization, compound 1 induced some vacuolizations and 8
      methoxypsoralen generated plenty of vacuoles and an empty space around the
      nucleus. Morphometrical data in HL60 cells turned out to be in accordance with
      the different action mechanisms existing between 8-methoxypsoralen and the two
      benzopsoralen derivatives; in HeLa cells we noted an increase in the nuclear area
      induced by all the three compounds. Only compound 1 caused the formation of
      echinocytes both in the dark and after UVA irradiation, suggesting the
      involvement of a mechanism not strictly related to DNA interaction and singlet
      oxygen production.

PMID- 9000264
TI  - Uptake of manganese and cadmium from the nasal mucosa into the central nervous
      system via olfactory pathways in rats.
AB  - In the olfactory epithelium the primary olfactory neurones are in contact with
      the environment and via the axonal projections they are also connected to the
      olfactory bulbs of the brain. Therefore, the primary olfactory neurones provide a
      pathway by which foreign materials may gain access to the brain. In the present
      study we used autoradiography and gamma spectrometry to show that intranasal
      instillation of manganese (54Mn2+) in rats results in initial uptake of the metal
      in the olfactory bulbs. The metal was then seen to migrate via secondary and
      tertiary olfactory pathways and via further connections into most parts of the
      brain and also to the spinal cord. Intranasal instillation of cadmium (109Cd2+)
      resulted in uptake of the metal in the anterior parts of the olfactory bulbs but
      not in other areas of the brain. This indicates that this metal is unable to pass
      the synapses between the primary and secondary olfactory neurones in the bulbs.
      Intraperitoneal administration of 54Mn2+ or 109Cd2+ showed low uptake of the
      metals in the olfactory bulbs, an uptake not different from the rest of the
      brain. Manganese is a neurotoxic metal which in man can induce an extrapyramidal
      motor system dysfunction associated with occupational inhalation of manganese
      containing dusts or fumes. We propose that the neurotoxicity of inhaled manganese
      is related to an uptake of the metal into the brain via the olfactory pathways.
      In this way manganese can circumvent the blood-brain barrier and gain direct
      access to the central nervous system.

PMID- 9000265
TI  - Food safety: a global perspective.
AB  - The health of the population of the U.S. is affected by many factors, not the
      least of which is its food supply. A major source of high quality animal protein
      comes from poultry, eggs, and meat. The major effect of personal habits and the
      environment, diet, tobacco, alcohol, are considered, along with the
      microbiological effect on foodborne illness and health. The inspection system for
      meat and poultry is reviewed, in light of the publication of significant
      revisions being instituted at this time. The role of research, regulatory reform,
      and political science is considered as supportive of food service and consumer
      education. Education of food service workers, institutional employees, and
      consumers is a responsibility that the land grant universities should take very
      seriously. Networking with associations like the National Restaurant Association
      and its regional affiliates will be invaluable in improving the health of the
      people of the U.S.

PMID- 9000266
TI  - Utilization of the sex-linked gene for imperfect albinism (S*ALS). 2. Yolk sac
      lipid utilization.
AB  - The gene for sex-linked imperfect albinism (S*ALS) has been associated with
      reduced early growth and slow utilization of the yolk sac contents. Neonatal
      growth was studied using albino and nonalbino full siblings that were dissected
      at 2-d intervals from Day 16 of incubation to 7 d after hatch. Fatty acid
      composition of the yolk, yolk sac membrane, and liver was determined to study
      neonatal lipid metabolism. At hatch, albinos had similar BW and lower (P < 0.01)
      liver weights, suggesting reduced lipid transfer from the yolk sac during late
      incubation. Nonalbinos started gaining weight at 3 d after hatch, 1 d earlier
      than albino chicks. Albinos had reduced growth (P < 0.01), larger yolk sacs (P <
      0.05), and similar (P > 0.05) yolk uptake from hatch to 7 d after hatch. Albino
      chicks also had lower body temperatures (P < 0.05) at 2, 4, and 6 d after hatch.
      Albinos had a slower rate of transfer of yolk lipids to the developing embryo in
      the last 2 d of incubation. The fatty acid composition of the yolk and yolk sac
      membrane was similar for both genotypes during the last 3 d of incubation, except
      for the level of stearic acid, which was higher (P < 0.05) for nonalbinos on Day
      18 of incubation for both tissues and at 1 d after hatch for the yolk. The fatty
      acid composition of the livers of albinos and nonalbinos were similar (P > 0.05)
      during the neonatal period. For both genotypes, the hepatic level of oleic acid
      increased to Day 20 of incubation, remained constant to 1 d after hatch, and
      decreased sharply thereafter. The major difference between the genotypes was a
      slower rate of transfer of yolk lipids to the developing albino embryo in the
      last 2 d of incubation.

PMID- 9000267
TI  - Associations of individual genomic heterozygosity, estimated by molecular
      fingerprinting, and of dam major histocompatibility complex with growth and egg
      production traits in layer chickens.
AB  - Growth and egg production data from F2 layer chickens produced from a mating of
      MHC-heterozygous B15B44 sires to B15B44 and B15B43 dams were analyzed for
      associations with the level of the individual's genomic heterozygosity and dam
      MHC. The F1 sires and dams were produced from mating of birds from two
      genetically distinct, highly inbred lines. Genomic heterozygosity (expressed as
      composite band frequency, CBF) was estimated based on the average proportion of
      shared bands of individual birds compared to a composite pool of Hinf I-digested
      DNA samples from the two inbred lines. Birds from dams of genotype B15B43 had
      significantly greater BW than progeny from B15B44 dams at 6 wk and thereafter.
      Dam MHC genotype differences were also significant for number of eggs laid from
      20 to 28 wk of age, with B15B43 progeny being superior. Negative regression
      coefficients at hatch, 32 and 44 wk were observed for the effect of CBF on BW of
      progeny from B15B43 dams and at hatch and 32 wk from progeny of pooled dam
      genotypes. Similarly, negative regression coefficients were observed for the
      association of CBF with number of eggs within progeny from the B15B44 dam MHC
      genotypes at 20 to 28 wk and total period recorded, and at 28 to 36 wk for
      progeny from B15B43 dams. The CBF regression coefficients and the differences
      among progeny based on dam MHC genotypes suggest that individual heterozygosity
      and MHC genotype may be associated with BW and egg production in chickens.

PMID- 9000268
TI  - The effect of beak trimming on two strains of commercial tom turkeys. 2. Behavior
      traits.
AB  - The influence of beak trimming of two strains of commercial male turkeys (Strains
      A and B) on behavior during the growing period was investigated. Poults were
      either left with beaks intact or arc beak trimmed at hatching. Strain by beak
      treatment interactions were generally lacking, indicating that these two strains
      responded similarly. Beak trimming did not influence tameness (as measured by
      response to a novel object at 16 wk), fearfulness (as measured by tonic
      immobility response at 18 wk), or resting behavior from 3 to 15 wk of age. When
      compared to birds with intact beaks, birds with trimmed beaks spent more time
      standing during the week of hatching and were observed eating more often at 2 wk
      of age. Strain B birds were more tame, less fearful, and rested more at 8 and 11
      wk of age than Strain A birds. Results of the current study indicate that the
      influence of arc beak trimming at hatching on behavior of male turkeys at
      hatching did not appear to have a lasting negative impact on their well-being.

PMID- 9000269
TI  - Effects of feeding Fusarium moniliforme culture material, containing known levels
      of fumonisin B1, in the young turkey poult.
AB  - The effects of feeding Fusarium moniliforme culture material, containing known
      concentrations of fumonisin B1 (FB1), were studied in turkey poults. Day-old
      poults were allotted randomly to dietary treatments containing 0, 0.41, 0.82,
      1.23, 1.64. 2.87, 4.10, 5.33, 6.56, and 7.79% fumonisin culture material (FCM).
      These levels of FCM supplied 0, 25, 50, 75, 100, 175, 250, 325, 400, and 475 mg
      FB1/kg of feed. Each dietary treatment was fed to six pen replicates of six
      poults each for 21 d. Poults fed FCM that supplied 325 to 475 mg FB1/kg diet had
      lower (P < 0.05) feed intakes and BW gains. Increased (P < 0.05) liver and
      pancreas weights were observed in poults fed FCM that supplied > or = to 175 mg
      FB1/kg. Poults fed FCM that supplied 400 and 475 mg FB1/kg diet had increased (P
      < 0.05) red blood cell counts and increased (P < 0.05) serum concentrations of
      gamma glutamyl transferase and aspartate aminotransferase. Compared with
      controls, poults fed FCM that supplied 25, and 75 to 475 mg FB1/kg had increased
      (P < 0.05) liver sphinganine:sphingosine ratios. Hepatocellular hyperplasia was
      mild at 75 and 100 mg FB1/kg diet, moderate to severe at 250 mg/kg FB1, and
      severe at 325 to 475 mg FB1/kg. Multifocal to generalized loss of cross
      striations and thinning of cardiomyocytes was observed in poults fed FCM that
      supplied 475 mg FB1/kg diet. Results indicated that diets containing < or = to
      1.23% FCM that supplied > or = to 75 mg FB1 /kg are toxic to young turkeys.

PMID- 9000270
TI  - Artificial neural network prediction of ascites in broilers.
AB  - An artificial neural network was trained to predict the presence or absence of
      ascites in broiler chickens. The neural network was a three-layer back
      propagation neural network with an input layer of 15 neurons (defining 15
      physiological variables), a hidden layer of 16 neurons, and an output layer of 2
      neurons (the presence or absence of ascites). Male by-products of a breeder
      pullet line were brooded at 32 and 30 C during Weeks 1 and 2, respectively. The
      training set for the neural network consisted of data from birds subjected to
      cool temperatures (18 C) to induce ascites. After training, the predictive
      ability of the neural network was verified with two new data sets. The second
      data set was from birds subjected to cool temperatures (18 C). The third data set
      was from birds subjected to clamping of the pulmonary artery to simulate the
      physiological processes involved in ascites (the temperature was 24 C). A
      comparison was made between laboratory diagnostic results and the neural network
      predicted ascites incidence. The neural network accurately identified the
      presence or absence of ascites in the first (training) set. Two false positives
      and one false positive were identified in the second and third verification sets,
      respectively. The birds identified as false positives were determined to be in
      the developmental stages of ascites before the occurrence of fluid accumulation.
      Artificial neural networks were found to effectively identify broilers with and
      without ascites.

PMID- 9000271
TI  - Effect of roxarsone and bacitracin methylene disalicylate on the development of
      immunity to Eimeria in broilers given a live coccidiosis vaccine.
AB  - No significant differences in the BW, feed intake, feed conversion, or mortality
      of broilers that had been vaccinated at 3 d of age with a live coccidiosis
      vaccine were observed irrespective of whether they had been given roxarsone,
      bacitracin methylene disalicylate, or both drugs in the feed. The weight gain of
      birds challenged with a high dose of the vaccine at 51 d was not significantly
      different from that of unchallenged birds and no lesions of Eimeria species were
      found in their intestines irrespective of the medication given. It is concluded
      that roxarsone and bacitracin methylene disalicylate do not interfere with the
      acquisition of immunity to Eimeria species in broilers.

PMID- 9000273
TI  - Administration of a coccidiosis vaccine to day-old turkeys via the eye and
      development of immunity to Eimeria species.
AB  - Day-old turkeys poults were given a live coccidiosis vaccine via the eye at the
      hatchery, and all poults produced oocysts in their droppings 7 d later. No
      oocytes were present in droppings of unvaccinated controls. The weight gain of
      vaccinated poults challenged at 3 wk of age with a mixture of three species of
      Eimeria was lower than that of unchallenged poults, indicating that they were
      susceptible to infection. No significant difference in weight gain was found when
      poults were challenged at 6 wk, however, indicating that they had acquired
      immunity to the species used for challenge.

PMID- 9000272
TI  - Effect of halofuginone (Stenorol) on Chukar partridge (Alectoris chukar).
AB  - This study was conducted to assess the effect of the coccidiostat halofuginone
      (Stenorol) on growth, feed consumption, and survival of Chukar partridge.
      Halofuginone was fed to three replicates (14 chicks per replicate) of chukar
      chicks from 2 to 7 d of age at levels of 0, 1.5, 3.0, 6.0 and 12 ppm. Mortality
      from 2 to 7 d was 0, 0, 0, 11, and 21 birds, respectively, by treatment. Seven
      day body weight showed a significant linear decrease with increasing halofuginone
      level (P < 0.01). On the 7th d, replicates receiving 6.0 and 12.0 ppm
      halofuginone were transferred to unmedicated feed for the remainder of the test
      due to excessive mortality. The other groups were continued until 6 wk of age. At
      6 wk, chicks fed 6 or 12 ppm halofuginone from 2 to 7 d and then unmedicated feed
      did not differ in body weight from those fed the unmedicated control diet. A
      significant difference in mortality was not observed among the other three
      treatment groups to 6 wk of age. A linear depression in 3-, 4-, 5-, and 6-wk body
      weight with increasing halofuginone level was observed within the first three
      treatment levels (P < 0.05). It was concluded that 1.5 ppm halofuginone depressed
      growth of young chukars and that 6 ppm resulted in increased mortality.

PMID- 9000274
TI  - Dietary lead alters fatty acid composition and membrane peroxidation in chick
      liver microsomes.
AB  - Inorganic Pb acetate is a pro-oxidant, and peroxidation damage to cellular
      membrane lipids, leading to membrane fragility and permeability, is a likely
      consequence of Pb poisoning. In addition to the systemic peroxidation that occurs
      in vivo, Pb-contaminated feedstuffs can contribute preformed peroxides.
      Treatments with dietary Pb that have been shown to increase tissue peroxide
      levels in animals may be related to the consumption of preformed peroxides from
      the diet. In the current study, we evaluated the possible separate effects of
      feed and systemic peroxides by administering equivalent doses of Pb
      acetatetrihydrate to chicks via either 1,500 ppm Pb in the diet or via gastric
      intubation. Peroxidation of lipids in hepatic microsomal membranes (assessed as
      malonyldialdehyde production) from birds intoxicated with Pb by either route of
      administration was more than double that of untreated controls. Also, both routes
      of Pb exposure doubled the concentration of hepatic microsomal arachidonic acid,
      a peroxidizable polyunsaturated fatty acid. In the data reported here, we show
      that tissue peroxide levels are unaffected by the method of oral Pb
      administration and thus, by inference, independent of peroxide content of the
      feed.

PMID- 9000276
TI  - Influence of vitamins E and C on the toxic effects of ochratoxin A and T-2 toxin
      in chicks.
AB  - The objective of this study was to determine whether two antioxidant vitamins,
      vitamins E and C, were able to counteract the production of lipid peroxides and
      the corresponding toxic signs of two important but diverse mycotoxins, T-2 toxin
      and ochratoxin A (OA). Experiment 1 was designed in a 3 x 3 factorial arrangement
      using three doses of vitamin E (dl-alpha-tocopheryl acetate) in the diet of
      Leghorn cockerels (required level according to NRC, 10x, and 100x requirements)
      and three toxin treatment [no toxin (Diets 1, 2, and 3), 4 mg T-2/kg of diet
      (Diets 4, 5, and 6), and 2.5 mg OA/kg of diet (Diets 7, 8, and 9)]. The
      experimental design for Experiment 2 was the same as for Experiment 1 except that
      Vitamin C (0, 200, and 1,000 mg/kg of diet) was used in place of vitamin E and
      the concentration of T-2 in Diets 4, 5, and 6 was increased to 5 mg/kg of diet.
      Six replicates were used per treatment with four birds per replicate. In both
      experiments, OA and T-2 decreased the performance of the chicks significantly.
      The concentration of uric acid in the plasma increased (P < 0.001) when OA was
      added to the diet, whereas the supplementation of the diet with vitamin E (100x
      the requirement) partially counteracted this effect (P = 0.07). The presence of T
      2, and especially OA, in the diet decreased the concentration of alpha-tocopherol
      in the liver (P < 0.001). Consistent with these findings were increased values of
      malondialdehyde (MDA) in the liver due to OA. In Experiment 1, vitamin E
      supplementation partially ameliorated the prooxidative effects of OA by
      decreasing the concentrations of MDA (P < 0.05). These data suggest that lipid
      peroxides are formed in vivo by T-2 and especially by OA and that these effects
      can be partially counteracted by an antioxidant such as vitamin E but not by
      vitamin C.

PMID- 9000275
TI  - Dietary marine algae promotes efficient deposition of n-3 fatty acids for the
      production of enriched shell eggs.
AB  - Two experiments were conducted to investigate the usefulness of a natural golden
      marine algae (MA) as a poultry ration supplement for the production of shell eggs
      rich in n-3 fatty acids (n-3 FA). This MA is unique due to a high concentration
      of docosahexaenoic acid (DHA; C22:6n-3) and the absence of other n-3 FA normally
      present in marine oils such as menhaden oil (MO). In the first experiment, 60 24
      wk-old Single Comb White Leghorn (SCWL) hens were divided among four dietary
      treatments, including a typical corn-soybean control (CON); 1.5% MO, supplying
      233 mg eicosapentaenoic acid (EPA) and 155 mg DHA per d; 2.4% MA, supplying 200
      mg DHA/d; and 4.8% MA, supplying 400 mg DHA/d. A second experiment using 96 56-wk
      old SCWL was conducted using the same diets. In both experiments, eggs were
      collected weekly for 4 wk for determination of egg production parameters and yolk
      FA content. Each week, yolk samples were extracted, methyl estered, and
      quantified using gas chromatography. Transient depression in egg and yolk weights
      were noted early in Experiment 1 in response to dietary 4.8% MA. Although egg and
      yolk weights were not affected in Experiment 2, egg production was significantly
      reduced in the 4.8% MA treatment. Egg production was unaffected due to diet or
      week in Experiment 1. In both experiments, yolk polyunsaturated profiles were
      significantly influenced by diet. Dietary n-3 FA supplementation significantly
      increased yolk total N-3 FA with concomitant reductions in yolk n-6 FA. Although
      hens fed MO were supplied predominantly EPA, the principal yolk FA deposited was
      DHA. Marine algae also promoted efficient yolk DHA deposition with the highest
      yolk DHA concentrations attained in eggs from hens fed 4.8% MA. These data
      indicate that utilization of MA as a direct source of dietary n-3 FA may provide
      an efficient alternative to current sources of n-3 FA available for the
      production of poultry products rich in n-3 FA.

PMID- 9000278
TI  - Effect of storage duration on the nutritional value of corn kernels for broiler
      chicks.
AB  - A study was carried out to evaluate the effect of storage duration of corn on its
      chemical composition (DM, protein, fat, amino acid, and fatty acids) and
      nutritional value for chicks, with an emphasis on AMEn. Freshly harvested whole
      grains were stored for 110 mo in covered galvanized iron cans, kept inside a
      storehouse. The AMEn content of the grains was determined in 10 experiments in
      which the corn was incorporated in a diet designated for the evaluation of AMEn
      by the substitution method. These determinations were carried out with male
      broiler chicks at 15 to 17 d of age. The chemical composition of the grains did
      not change during storage, except for a significant (P < 0.02) increase in lysine
      and a decrease in valine levels. Moreover, the AMEn content was not affected
      significantly (P > 0.05) by storage duration. It is concluded, therefore, that
      storing corn grains for 110 mo, under proper conditions, does not adversely
      affect their nutritional value.

PMID- 9000277
TI  - Efficacy of supplemental microbial phytase at different dietary calcium levels on
      growth performance and mineral utilization of broiler chickens.
AB  - A 3-wk feeding trial with 240 sexed, day-old broiler chickens was conducted to
      determine the efficacy of microbial phytase at different levels of dietary Ca on
      performance and utilization of minerals in broiler chickens fed a low-P corn
      soybean diet. The experimental design was a 3 x 2 factorial arrangement of
      treatments; Ca at 0.6, 1.0, and 1.25% and phytase at 0 and 600 phytase U/kg diet.
      Phytase supplementation, regardless of Ca level, increased (P < or = 0.005) feed
      intake, (P < or = 0.0001) body weight, and (P < or = 0.025) feed efficiency at 21
      d; the optimum levels of body weight, feed intake, and feed efficiency were
      obtained with low (0.6%) dietary Ca plus phytase. Retentions of P, Ca, and N were
      increased (P < or = 0.05) by phytase supplementation. Although maximum retentions
      of P and N were obtained at the 1.0 and 1.25% Ca levels, respectively, they were
      not significantly different from the values obtained at 0.6% Ca. The increasing
      level of dietary Ca decreased plasma P ( P < or = 0.05) and Cu (P < or = 0.06).
      Phytase supplementation had the opposite effect; i.e., increased plasma P (P < or
      = 0.03) and Cu (P < or = 0.02). The maximum level of plasma P was obtained with
      phytase at the 1.0% Ca level, but this value was not significantly different from
      the value obtained with phytase at the 0.6% Ca level. Phytase supplementation
      increased (P < 0.04) the ash content of both tibia head and shaft but had no
      effect on mineral contents in the ash. The optimum level of ash content was
      observed with the 0.06% Ca diet plus phytase. The results show that microbial
      phytase supplementation to a low P diet improved growth performance and mineral
      utilization in broiler chickens. Dietary Ca levels had a significant effect on
      the response to phytase; the optimum growth performance and mineral utilization
      were achieved at the low (0.6%) level of dietary Ca supplemented with phytase.

PMID- 9000279
TI  - A novel 29-kDa chicken heat shock protein.
AB  - The family of small heat shock proteins is the more variable among the highly
      conserved superfamily of heat shock proteins (HSP). Using a metabolic labeling
      procedure with tissue explants, we have detected in chickens a new member of the
      small HSP family with an apparent molecular weight of 29-kDa. This protein was
      induced in broiler chickens' heart muscle and lungs following an in vivo heat
      stress. The 29-kDa band appears after 3 h of heat stress, much later than the
      induction of HSP 90, HSP 70, and HSP 27. The late onset of induction suggests
      that HSP 29 plays a more specific role of a "second stage defense protein".

PMID- 9000281
TI  - Alkaline phosphatase activity in the theca of ovarian follicles of the hen
      throughout follicular development.
AB  - Within the hen's ovary, the theca tissue of small follicles that have not yet
      entered the preovulatory hierarchy is a major contributor to ovarian
      steroidogenesis. Relatively little is known about developmental stages in the
      theca layer within this pool of follicles and of the histological properties of
      this tissue. In pigs and sheep, alkaline phosphatase activity has been identified
      in the theca of preovulatory follicles and in theca-derived cells in the corpus
      luteum. The objectives of this study were to document morphological changes in
      the theca layer through pre- and postovulatory follicular development, and to
      assess alkaline phosphatase activity at these developmental stages. Ovarian
      tissue containing small white, large white, small yellow, large yellow, and
      postovulatory follicles (POF) was obtained from mature White Leghorn hens and
      embedded in either methacrylate for morphological assessment or paraffin for
      alkaline phosphatase histochemistry. Alkaline phosphatase activity was found to
      be specific for cells of the theca interna in preovulatory follicles. Activity
      was first detectable in very small white follicles, the earliest stage in which
      the theca interna could be distinguished from the theca externa, and highest in
      the yellow yolky follicles. After ovulation, activity decreased to undetectable
      levels by the POF4 to 5 stages in POF within 4 to 5 d after ovulation. This study
      has shown that in the domestic hen, alkaline phosphatase activity is present in
      cells adjacent to the basal lamina of the theca interna of preovulatory follicles
      and POF up to 4 to 5 d after ovulation. Identification of the functional
      significance of this histological reaction will provide new information on
      ovarian function in the hen.

PMID- 9000280
TI  - Characterization of a cDNA encoding an alpha thyroid hormone receptor in muscovy
      duckling.
AB  - A complementary deoxyribonucleic acid (cDNA) clone encoding an alpha thyroid
      hormone receptor (TR alpha) from muscovy duckling liver was isolated and
      sequenced. Comparison with the chicken TR alpha sequence showed a high degree of
      homology. Despite 45 nucleotide substitutions, the deduced peptide sequence was
      similar. This cDNA was used as a probe to characterize the TR alpha mRNA
      transcripts expressed in muscovy duckling liver and skeletal muscle.

PMID- 9000282
TI  - The male contribution to broiler breeder heat-induced infertility as determined
      by sperm-egg penetration and sperm storage within the hen's oviduct.
AB  - The purpose of the present study was to define the role of the male broiler
      breeder in heat-induced infertility. Seventy-two Arbor Acres roosters were
      individually caged at 21 wk of age and divided equally among three heated (H) and
      three control (C) temperature chambers. Control temperature chambers were held at
      21 C. After an 8-wk pretreatment period (20 C), an 8-wk treatment period was
      conducted in which the temperature in all three of the H chambers was varied from
      week to week according to the following schedule: Week 1, 27 C; Week 2 through
      Week 4, 32 C; and Week 5 through Week 8, 21 C. On a weekly basis, semen was
      pooled by room and inseminated into 12 groups of 10 hens each (2 groups per
      room). During the 1st wk when males were maintained at 27 C for 12 h, in vivo
      sperm-egg penetration was reduced by 48% as compared to data obtained when males
      were maintained at 21 C. Fertility, in vivo sperm-egg penetration, and
      uterovaginal sperm storage were decreased when semen from males exposed to 32 C
      was used to inseminate hens as compared to insemination with semen from C males.
      However, during this same period, the ability of sperm to bind and penetrate the
      egg, as determined by in vitro sperm-egg penetration, was similar between sperm
      from C and H males. After lowering the temperature in the H chambers back to 21
      C, in vivo sperm-egg penetration as a result to insemination with semen from H
      males was analogous to results obtained when C males were used for insemination.
      Immediately after decreasing the temperature in the H chambers, fertilization of
      eggs by sperm from H males increased to a level similar to that obtained when
      eggs were fertilized by sperm from C males but then declined again during the
      later weeks.

PMID- 9000283
TI  - Acute high environmental temperature and calcium-estrogen relationship in the
      hen.
AB  - Much is known about the effects of high environmental temperature (HT) on egg
      production, but very little is understood about the mechanisms that underlie
      them. Two experiments were conducted to examine the effects of acute heat stress
      on circulating estradiol, on calcium uptake by gut tissue, on bone resorption,
      and on the dynamic relationship between estradiol and calcium in the hen during
      one ovulatory cycle. In one study, hens were moved individually and randomly into
      a hot [HT: temperature (T) = 35 C, relative humidity (RH) = 50%; n = 18] or a
      control, thermoneutral (TN: T = 23 C, RH = 50%; n = 18) environment immediately
      after a mid-sequence oviposition and brachial vein cannulation. Blood samples (2
      mL) were collected every 3 h for 21 h for ionized calcium (Ca2+) and pH
      determinations and from which aliquots were frozen for 17 beta-estradiol (E2),
      total calcium (TCa), and inorganic P analysis. Excreta and urine were assayed for
      TCa and hydroxyproline (OHPr), respectively. A second study was conducted to
      determine the effects of HT (T = 35, H = 50%, 12 h) vs TN (T = 23 C, RH = 50%, 12
      h) on the ability of duodenal cells to take up calcium (CaT). Blood pH and
      calcium responded to HT as expected (pH increased, Ca2+ decreased, and TCa
      decreased) and the cyclic pattern of Ca2+ in blood was abolished. The ratio of
      Ca2+:TCa decreased sharply at approximately the onset of shell calcification in
      control hens, but in HT hens there was no clear change in the ratio of any point
      in the cycle. The pattern of E2 typical of hens under normal conditions was
      significantly depressed in plasma of HT hens. Calcium uptake by duodenal
      epithelial cells of HT hens was lower than in TN hens. There was a clear inverse
      correlation between blood Ca2+ and urine OHPr in TN hens (r2 = -73, P = 0.0021)
      but not in HT hens (r2 = -27, P = 0.32). In addition to alterations in acid-base
      balance and the status of Ca2+, diminished ability of duodenal cells to transport
      calcium may be a critical factor in the detrimental effects of heat stress on egg
      production (numbers), eggshell characteristics, and skeletal integrity often
      documented in the laying hen.

PMID- 9000284
TI  - N-acetyl-beta-D-glucosaminidase as a marker of renal damage in hens.
AB  - Urinary N-acetyl-beta-D-glucosaminidase (NAG) is an early physiological indicator
      of renal damage in several mammalian species. A study was conducted to confirm
      occurrence of NAG in hen urine, to establish baseline urinary NAG in laying hens,
      and to assess the feasibility of using the enzyme as a marker of renal damage in
      hens. Hy-Line hens were used in a completely randomized block design in the first
      part of the study. Urine was collected at 4 to 6, 6 to 10, 10 to 14, and 14 to 18
      h, and serum at 4, 6, 10, and 14 h postoviposition, and assayed by
      spectrophotometry for NAG. Kidney tissue from additional hens was assayed
      histochemically for NAG. Serum NAG (range: 0.11 to 0.14 mU/mg protein) was found
      to be several orders of magnitude lower than urine NAG (6.44 to 12.27 mU/mg
      protein). Urine NAG increased from 4 to 6 h through 14 to 18 h, indicating that
      time of collection is critical in order to utilize the enzyme as a valid marker
      for laying hens. A preliminary study with five hens indicated that 10 d of
      treatment with liquid cholecalciferol (D3) supplement (three times the
      recommended level) were not enough to detect renal damage on the basis of
      significant changes in urine (NAG, but elevated urine NAG was detected at 40 d of
      D3-supplementation. Overall the results indicate that NAG in urine of laying hens
      is a potentially useful diagnostic marker of renal damage.

PMID- 9000285
TI  - Developmental stages of primary oocytes in turkeys.
AB  - Little is known about the growth and differentiation of the primary oocyte in the
      sexually mature chicken or turkey hen. In this study, primary oocytes from turkey
      hens in egg production were examined by light and electron microscopy. Based on
      oocyte and germinal vesicle (GV) diameters and organelle morphology and
      distribution, the sequential development of the primary oocyte was divided into
      five stages. No Balbiani body was observed in Stage I oocytes (< 80 microns in
      diameter). Pleomorphic mitochondria were localized around the GV and
      multivesicular bodies were scattered in the ooplasm. By Stage II (81 to 150
      microns), the Balbiani body was observed adjacent to the GV. Pleomorphic
      mitochondria, macrobodies, and smooth endoplasmic reticulum (SER) were associated
      with the Balbiani body. Lipid droplets were predominantly localized to the
      periphery of the oocyte. The Balbiani body was partially dispersed by Stage III
      (151 to 350 microns) and associated organelles appeared in clusters in the
      ooplasm. Golgi and SER were observed immediately subjacent to the oolemma. Stage
      IV oocytes (351 to 500 microns) were characterized by the absence of the Balbiani
      body, a more centrally located GV, and the redistribution of the mitochondria to
      the periphery of the oocyte. Throughout the ooplasm was vesicular SER. By Stage V
      (501 to 800 microns), zonation of the organelles was completed with the
      mitochondrial ring immediately subjacent to the oolemma and a concentric layer of
      lipid droplets subjacent to the mitochondrial ring. The GV was in the periphery
      of the oocyte. Organelle and inclusion redistribution and organelle pleomorphism
      were presumed to be reflective of increasing metabolic and transport requirements
      of the growing oocyte in the mature turkey hen.

PMID- 9000286
TI  - Secretion of luteinizing hormone during a forced molt in turkey hens.
AB  - The secretory pattern of luteinizing hormone (LH) was determined in turkey hens
      during a forced molt induced by water (1 d) and feed (5 d) restriction and
      switching the photoschedule from 14 h light (L):10 h dark (D) (long-day) to
      6L:18D (short-day), the 1st d of feed and water restriction. Serial blood samples
      were collected from six hens (every 10 min for 6 h, then every 4 min for 2 h) at
      four different times during the trial. The first serial bleeding was done at the
      end of egg laying and 1 d before forced molting was initiated; the second 7 d
      after start of forced molting and short-day lighting; the third after 49 d of
      short-day lighting, and the fourth after 56 d of short-day lighting and 2 day
      after returning the hens to long-day lighting. Egg production stopped by 5 d
      after initiation of forced molting. Egg production reinitiated by 34 d (range 22
      to 34 d) after returning to long-day lighting. Overall and baseline concentration
      of LH were low at the end of egg laying and 7 d after the start of forced
      molting. Number and amplitude of pulses of LH were also low at these times.
      Overall and baseline concentrations of LH remained low after 49 d of short-day
      lighting, with no change in number of LH pulses per 8 h. However, the amplitude
      of LH pulses was increased at this time in comparison to just after initiation of
      forced molting. At 2 d after switching to long-day lighting, increases in
      overall, baseline, and number of pulses of LH were detected. Peak amplitude did
      not change 2 d after switching to the long-day photoperiod. It was concluded that
      in turkey hens at the end of a relatively long laying period, baseline LH is low
      and does not decrease during a forced molt and subsequent reconditioning period.
      Relatively large increases in circulating LH are induced by exposing the
      reconditioned hens to the long-day photoperiod of 14L:10D, and this increase was
      associated with an increase in overall and baseline LH concentrations and LH
      pulse frequency.

PMID- 9000287
TI  - Cardio-pulmonary function during acute unilateral occlusion of the pulmonary
      artery in broilers fed diets containing normal or high levels of arginine-HCl.
AB  - Cardio-pulmonary function was measured in male broilers reared on diets
      formulated to contain 1.5% arginine (NORMAL group) or 2.5% arginine (ARGININE
      group). A snare placed around the right pulmonary artery permitted acute shunting
      of the entire cardiac output (CO) through the left pulmonary artery, resulting in
      sustained increases in blood flow (BF) through the left lung in both groups. The
      unilateral increase in BF was accompanied by sustained increases in pulmonary
      arterial pressure (PAP) and pulmonary vascular resistance (PVR) in the NORMAL
      group. However, following initial transient increases in PAP and PVR in the
      ARGININE group, subsequent pulmonary vasodilation gradually reduced PVR, and thus
      PAP, in spite of the ongoing elevation of BF through the left lung. The capacity
      of the pulmonary vasculature in the ARGININE group to accommodate an increased BF
      at a normal PAP accounts for the previously reported lower incidence of pulmonary
      hypertension syndrome (PHS, ascites) in cold-stressed broilers fed supplemental
      dietary arginine. Hypoxemia and respiratory acidosis ensued rapidly in both
      groups after tightening the pulmonary artery snare, in spite of a compensatory
      increase in the respiratory rate. The gradual return of PVR and PAP to presnare
      levels in the ARGININE group did not eliminate the concurrent ventilation
      perfusion mismatch caused by the increased rate of BF through the left lung.
      Tightening the pulmonary artery snare caused mean systemic arterial pressure
      (MAP) to drop from control levels of approximately 98 mm Hg to sustained
      hypotensive levels of approximately 65 mm Hg in both groups. This systemic
      hypotension was caused by decreases in CO and total peripheral resistance (TPR).
      The reduction in CO were caused by reduction in stroke volume (SV) rather than
      heart rate (HR), suggesting that acutely tightening the pulmonary artery snare
      increased PVR sufficiently to impede left ventricular filling. Accordingly, the
      maximum increment in PAP attainable by the right ventricle during acute increases
      in PVR apparently was inadequate to propel the entire CO through the pulmonary
      vasculature, setting the stage for the congestive right-sided pooling of blood
      routinely associated with PHS in broilers.

PMID- 9000289
TI  - Attitudes toward older adults reported by young adults: variation based on
      attitudinal task and attribute categories.
AB  - Negative attitudes toward older adults are thought to be prevalent within the
      American culture. However, research on attitudes presents conflicting results. In
      this study, 2 factors were hypothesized to influence reported attitudes toward
      older adults: the attitudinal instrument used (a rating task vs. an open-ended
      task) and the types of attributes assessed (cognitive, personal-expressive, and
      physical). The results confirmed that attitudes toward older adults were negative
      relative to attitudes toward younger and middle-aged adults, but the pattern of
      negativity differed by task and attribute category. Negativity was most apparent
      in the open-ended task and in the physical category. These results indicate that
      although general, negative stereotypes may exist, older adults are viewed as
      multidimensional people with both positive and negative attributes.

PMID- 9000288
TI  - Processing temperature and moisture content effects on the texture and
      microscopic appearance of cooked fowl meat gels.
AB  - New aseptic processes are being used and refined to produce convenient, shelf
      stable liquid products containing meat particles. These processes utilize high
      temperature, short time thermal treatments to minimize food quality change;
      however, little research has been conducted on the effects of this process on the
      texture of meat from mature hens traditionally used for canning. The objective of
      this study was to examine textural and structural changes in meat structure due
      to different high temperature (HT) heat treatments and meat moisture contents
      were examined by use of electron microscopy and torsion analyses. Cooked gels of
      different moisture contents (71.2 to 74.8%) were formulated from spent fowl
      breast meat and exposed to processing temperatures of 120 or 124 C. The HT
      processing resulted in stronger (tougher) meat gels that were more deformable
      (more chewy) than gels that were not processed by HT. Water added prior to
      cooking was not retained in samples that were cooked and then processed at 124 C,
      but was retained in the samples processed at 120 C. Electron micrographs showed a
      more organized and open gel structure in the samples with higher moisture content
      and lower temperature (120 C) processing compared to the lower moisture and
      higher (124 C) temperature treatments.

PMID- 9000290
TI  - Relationship of physical disease and functional impairment to depression in older
      people.
AB  - Physical disease is commonly considered a risk factor for depression among older
      adults. However, this pattern is not consistently supported, and a theoretical
      framework for understanding such a relationship has not been articulated. P.M.
      Lewinsohn, H. Hoberman, L. Teri, and M. Hautzinger's (1985) integrative model of
      depression predicts that disease will be a risk factor for depression only when
      disease results in functional impairment, and that impairment in the absence of
      disease is also a risk factor for depression. The authors tested these
      predictions in a community-based sample of older adults followed longitudinally
      and found that functional impairment was a significant risk factor for
      depression, regardless of disease status. Disease was not a significant predictor
      of major depression, nor did it interact with impairment to predict depression.

PMID- 9000291
TI  - Spousal similarity in subjective well-being: the Cardiovascular Health Study.
AB  - This study examines the extent to which one spouse's subjective well-being
      predicts that of the partner (N = 1,040 spousal pairs, 65 years or older). Prior
      research is extended in two ways: (a) The similarity of both affective domains
      (depressive symptoms, feelings about life as a whole, and satisfaction with the
      meaning and purpose of life) and nonaffective domains (perceived health) are
      examined, and (b) known predictors of well-being in older adults
      (sociodemographic variables, self and spouse health status variables, and
      exposure to common environmental events) are statistically controlled. Results
      indicate that one spouse's assessments of well-being and depression predict the
      other's well-being even after controlling for known predictors of these outcomes.
      Given the similarity of findings for affective and nonaffective domains, multiple
      mechanisms, including contagion, mate selection, and common environmental
      influences, are speculated as likely to contribute to this phenomenon.

PMID- 9000292
TI  - Sources of tension in the aging mother and adult daughter relationship.
AB  - This study explored sources of tension in the aging mother-adult daughter
      relationship. Forty-eight dyads of healthy mothers over the age of 70 years (mean
      age = 76 years) and their adult daughters (mean age = 44 years) were interviewed
      individually and then together about their relationship. Responses to questions
      about tension were coded as referring to intrusiveness, exclusion, inappropriate
      care of self or other, or as referring to general habits or traits. The term
      developmental schism is introduced to explain possible sources of tension in this
      relationship. Aging mothers and middle-aged daughters are at different points in
      their adult development; developmental discrepancies may foster interpersonal
      tension in their relationship. Mothers and daughters who described sources of
      difficulty that were not related to developmental differences had more positive
      regard for the relationship.

PMID- 9000293
TI  - Characteristics of associative learning in younger and older adults: evidence
      from an episodic priming paradigm.
AB  - Two experiments investigated age differences in the encoding of associative
      information during a speeded naming task. In both experiments, semantically
      unrelated prime-target word pairs were presented 4 times, in either massed or
      spaced fashion, during the learning phase. An immediate or delayed test trial was
      presented following the fourth presentation. In Experiment 1, participants named
      both the primes and the targets. Younger and older adults showed similar benefits
      when naming targets that were part of a consistent prime-target pairing compared
      with targets presented with different primes at each presentation. In Experiment
      2, participants named only the target word. Younger adults showed a benefit for
      consistently paired words, whereas older adults showed no benefit for
      consistently paired words. The results of the test trials showed a greater
      benefit for massed repeated words than for spaced repeated words at the immediate
      test and a reversed pattern at the delayed test. This spacing by test delay
      interaction was evident in response latency in Experiment 1 and in cued recall
      performance in Experiment 2.

PMID- 9000294
TI  - Mediators of long-term memory performance across the life span.
AB  - An individual-differences approach was used to examine the component processes
      that predict episodic long-term memory performance. A total of 301 participants
      ages 20-90 received a 7-hr cognitive battery across 3 days. Key constructs
      hypothesized to affect long-term memory function were assessed, including
      multiple measures of working memory and perceptual speed. Latent-construct,
      structural equation modeling was used to examine the relationship of these
      measures and age to different types of long-term memory tasks. Speed was a key
      construct for all 3 types of memory tasks, mediating substantial age-related
      variance; working memory was a fundamental construct for free and cued recall but
      not spatial memory. The data suggest that both speed and working memory are
      fundamental to explaining age-related changes in cognitive aging but that the
      relative contributions of these constructs vary as a function of the type of
      memory task.

PMID- 9000295
TI  - Adult age differences in recall of performed and nonperformed items.
AB  - Memory for performed cognitive activities (e.g., psychometric tests of
      intelligence), for performed brief actions (e.g., hand wave), and for
      nonperformed items (e.g., written words) was assessed for 102 older and 101
      younger adults. Although enactment improved recall, the beneficial effects of
      enactment were the same for both age groups. In fact, more than 80% of the age
      related variance in memory for performed items was shared with memory for
      nonperformed items. Working memory and perceptual speed were important to the age
      differences in memory for both types of items. Performed and nonperformed items
      showed different serial position effects. However, the correlation between memory
      for the 2 types of items was high, especially for older adults, suggesting that
      the 2 types of memory share many common processes.

PMID- 9000296
TI  - Episodic remembering in a population-based sample of nonagenarians: does major
      depression exacerbate the memory deficits seen in Alzheimer's disease?
AB  - Population-based samples of normal old adults and people with major depression
      (MD), Alzheimer's disease (AD), and coexisting MD and AD (MD + AD) between 90 and
      100 years of age were assessed in face recognition, word recall, and object
      recall. Results indicated a consistent pattern across tasks: no differences
      between the normal old and the MD participants or between the AD and MD + AD
      participants in any task, a clear performance decrement in the AD and MD + AD
      participants in all task variables reflecting long-term episodic memory, and no
      group differences in those variables reflecting short-term memory. These data
      suggest that depression in very old age may not exacerbate the episodic memory
      deficit that accompanies AD. Further, differences between normal old and MD
      participants in episodic memory tasks appear to be negligible among the oldest
      old. The general lack of effects of MD may be due to the fact that those symptoms
      of this disease that are most likely to affect memory functioning (e.g., loss of
      energy, concentration difficulties) are common in AD as well as in nondepressed
      people in the 10th decade of life.

PMID- 9000297
TI  - Aging, cognitive resources, and declarative learning.
AB  - A battery of cognitive tasks designed to assess information-processing speed,
      working memory capability, and declarative learning was administered to a cross
      sectional sample of 477 adults ranging in age from 17 to 86 years. Results showed
      significant age-related decrements in all three constructs. A variety of
      structural equation models was fit to the results. The preferred model on
      empirical and conceptual grounds was one that showed (a) working memory
      capability as the most important mediator of age effects in declarative learning;
      (b) working memory capability as the mediator for the effects of general
      processing speed on declarative learning; and (c) differentiation among verbal,
      numeric, and spatial processing speed and between verbal and spatial working
      memory capability.

PMID- 9000298
TI  - The moderating influence of physical fitness on age gradients in vigilance and
      serial choice responding tasks.
AB  - The moderating influence of physical fitness on age gradients in measures
      obtained from vigilance and serial choice responding tasks is examined in a
      sample of 90 postal workers. Physiological data relating to aerobic fitness
      determined fitness level within 2 age groups: younger participants ages 18 to 30
      years (M = 25.19; 24 men, 24 women) and older participants ages 43 to 62 years (M
      = 49.19; 20 men, 22 women). A performance decrement across time was found in
      several measures, and some variation as a function of age was apparent. However,
      post hoc statistical analyses did not indicate this was due to older adults
      underperforming younger adults. According to predictions, significant Age x
      Fitness interactions showed older less fit workers to consistently underperform
      other participants. The findings suggest that older less fit individuals have
      lower signal sensitivity and processing speed than older fitter people and
      younger individuals. Results are discussed in relation to underlying
      physiological mechanisms.

PMID- 9000300
TI  - Guidelines on the nutritional assessment of infant formulas. Report of the
      Working Group on the Nutritional Assessment of Infant Formulas of the Committee
      on Medical Aspects of Food and Nutrition Policy.

PMID- 9000299
TI  - Depressive symptoms across older spouses: longitudinal influences.
AB  - Cross-sectional findings that depressive symptoms in one older spouse influence
      those of the other and that marital closeness increases the influences (R.B.
      Tower & S.V. Kasl, 1995) were tested longitudinally. Independent interviews in
      1982, 1985, and 1988 with spouse-pairs who participated in the Established
      Populations for the Epidemiologic Study of the Elderly showed that changes in
      depressive symptoms in one older spouse contributed to changes in depressive
      symptoms in the other. For wives in 1985 and for husbands in 1988, a spouse's
      baseline depressive symptoms also contributed independent variance to an increase
      in respondent's score on the Center for Epidemiologic Studies Depression Scale.
      These findings were stronger when a couple was close. These results held when
      known intrapersonal risk factors and the health status of the spouse were
      controlled.

PMID- 9000301
TI  - Respiratory health effects of exposure to environmental tobacco smoke.
AB  - During the last 25 years, several hundred papers have been published on the
      respiratory health effects of environmental tobacco smoke (ETS). Various
      independent assessments have concluded that ETS causes lung cancer in adult
      nonsmokers and increases the risk of various noncancer effects, principally in
      children. The effects on children include pneumonia, bronchitis and bronchiolitis
      in young children; chronic middle ear effusion; increased frequency and severity
      of attacks among asthmatics; possible induction of asthma in previously
      asymptomatic individuals; small reductions in lung function; and symptoms of
      upper respiratory tract irritation. In nonsmoking adults, ETS exposure is
      associated with irritation of the eyes, nose, and throat, and with wheezing,
      symptoms of bronchitis, shortness of breath, and decreased lung function. The
      results of recent studies not only confirm and strengthen the above findings but
      also provide strong suggestive evidence that ETS causes sinonasal cancer and is a
      risk factor for sudden infant death syndrome. To mitigate such a preventable
      environmental health impact, public health measures to reduce involuntary ETS
      exposure are warranted.

PMID- 9000302
TI  - Thermoregulatory aspects of environmental exposure to anticholinesterase agents.
AB  - Anticholinesterase (antiChE) agents can be highly toxic to birds and mammals and
      constitute a major proportion of the pesticides used throughout the world.
      AntiChEs consist of the organophosphates (OP), which irreversibly inhibit the
      enzyme acetylcholinesterase (AChE), and the carbamates (CB), which reversibly
      inhibit AChE. AChE inhibition elicits cholinergic stimulation in the central
      nervous system and in peripheral tissues and organs, which can lead to marked
      dysfunction of homeostatic systems, including temperature regulation. The control
      of body temperature uses cholinergic pathways in the integration and central
      processing of thermal information, as well as in the control of thermoeffector
      responses. Hence, the cholinergic stimulation elicited from exposure to antiChEs
      has profound effects on body temperature at rest as well as during exercise.
      Ambient heat and cold stress can also modulate the animal's sensitivity to
      antiChE exposure. After exposure to most OPs, rodents and other small species
      undergo a marked hypothermic response lasting up to 24 hours. On the other hand,
      humans exposed to OP pesticides rarely become hypothermic but rather experience a
      fever that may last many days. Recent studies monitoring body temperature in OP
      exposed, telemetered rats demonstrated that the initial hypothermic response is
      followed by a period of hyperthermia lasting several days. That the hyperthermia
      can be blocked with administration of sodium salicylate suggests that the
      hyperthermia is a fever. Thus, the antiChE-induced effects on body temperature
      and other physiological systems cannot be explained solely by the immediate
      consequences of AChE inhibition and stimulation of cholinergic systems. Research
      into the mechanisms of action of antiChE toxicity will be improved with a better
      understanding of their effects on temperature regulation.

PMID- 9000303
TI  - The epidemiology of atopic diseases in Germany: an east-west comparison.
AB  - This review summarizes studies comparing the epidemiology of asthma, allergic
      rhinitis, and atopic dermatitis in eastern versus western German populations.
      These studies clearly revealed that the prevalence of physician-diagnosed
      allergic rhinitis was higher in western Germany than in eastern Germany. The rate
      for asthma also tended to be higher in western than in eastern populations,
      whereas a tendency for less atopic dermatitis was found in western German
      children. When sensitization rates, as measured by RAST and skin-prick tests,
      were compared, a clear increase was found in western versus eastern young-adult
      German populations. This phenomenon may be related to exposure to different
      allergens, such as those associated with nutritional patterns or pet ownership,
      as well as to different environmental factors, such as outdoor and indoor
      pollutants. If lifestyle or environmental factors play a role in developing
      allergic sensitization, then one would expect the rates of sensitization in
      eastern and western Germany to converge as the two societies become more similar.

PMID- 9000304
TI  - Impact of physical activity and sport on the immune system.
AB  - This review describes how exercise and physical training affect the immune
      system. Although many immune functions are stimulated by moderate physical
      activity, more vigorous effort and periods of heavy training suppress various
      immune response parameters. Experimental studies from our own laboratories and
      elsewhere illustrate that cellular infiltration of the active muscle is
      accompanied by phagocyte activation, suppressed NK-cell function, impaired
      lymphocyte proliferation, decreased in-vitro immunoglobulin production, pro
      inflammatory eicosanoid release, cytokine cascade activation, and altered
      expression of cytokine receptors. Examples cover deliberate heavy training;
      single bouts of fatiguing, submaximal work; repeated bouts of exercise; and ultra
      long distance athletic events. In young adults, age, environment, and light
      physical training do not change immune-response parameters. Parallels between
      immune impairment after vigorous exercise and reactions to surgical sepsis are
      noted. Vigorous exercise probably induces subclinical muscle injury and an
      associated inflammatory response. Heavy exercise may be a useful experimental
      model for developing more effective treatments for sepsis. For protection average
      athletes may take the anti-oxidant vitamins C and E and non-steroidal
      inflammatory drugs, if the muscles show signs of an inflammatory reaction. Top
      level athletes have received immunoglobulin preparations.

PMID- 9000305
TI  - Recombinant DNA technology: a 20-year occupational health retrospective.
AB  - During the past 20 years of recombinant DNA research and its commercial
      applications, neither unique occupational-health risks nor adverse effects from
      accidental occupational recombinant microorganisms has been reported. Such
      injuries as acid splashes, CNS-depressant effects from over-exposure to solvents,
      and infections may occur in all types of chemistry and microbiology laboratories.
      Because of the relative inexperience with the emerging technology of gene
      therapy, however, including possible vector replication or recombination, further
      vigilance in monitoring the safety of their applications is required.

PMID- 9000306
TI  - Exposure assessment--a challenge for occupational epidemiology.

PMID- 9000307
TI  - Quantification of historical exposures in occupational cohort studies.
AB  - Relatively few investigators have estimated quantitative exposure levels in
      epidemiologic studies, and, for those that have, few have discussed the strengths
      and weakness of their estimation method with respect to other methods. This paper
      reviews the steps for developing quantitative exposure estimates that have been
      used in published studies. First, the qualitative considerations to be evaluated
      in the selection of the agent to be estimated (i.e., the disease mechanism, the
      effects of exposure mixtures and interactions, the physical state of the agent,
      and the routes of exposures) are discussed. Considerations for developing
      exposure groups are then presented, including work history and exposure
      information characteristics, the homogeneity of exposures within exposure groups,
      the exposure estimation method, and the disease risk analyses to be performed.
      The various exposure estimation approaches are reviewed for their strengths and
      weaknesses, including the calculation of the mean exposures from existing
      exposure measurements, statistical models, measurement data from surrogate
      exposures, and professional judgment. Recommendations for future studies are
      provided.

PMID- 9000308
TI  - Exposure to 60-Hz magnetic and electric fields at a Canadian electric utility.
AB  - OBJECTIVES: The purpose of this study was to estimate exposure to extremely low
      frequency (ELF) magnetic and electric fields in the Quebec electrical utility
      Hydro-Quebec. METHODS: Personal exposures to ELF magnetic and electric fields
      were measured for workers randomly selected from 32 job categories at Hydro
      Quebec. Weekly arithmetic and geometric means, and other indices of exposure were
      estimated from 465 worker-weeks of data. RESULTS: By job category, the arithmetic
      means of the ELF magnetic field ranged from 0.09 to 2.36 microT. Those of the ELF
      electric field exposures ranged from 2.5 to 400 V.m-1. Within each field,
      correlations of either the arithmetic or geometric means with alternative
      indices, including an index of the time rate of change, were generally high (r >
      or = 0.8). Exceptions were the 20th percentile of the electric means and the
      proportion of time above 12.4 and 100 microT. The day-to-day variation of
      exposure was greater than the variation between workers. The median between-day
      and between-worker components of variance (as geometric standard deviations) by
      job category were 2.13 and 1.71 for magnetic fields (2.24 and 1.81 for electric
      fields). CONCLUSIONS: Substation workers, hydroelectric generating station
      operators, and cable splicers showed the highest arithmetic means for 60-Hz
      magnetic fields above 1 microT. For 60-Hz electric fields, forestry workers,
      equipment electricians in 735 kV substations, and distribution linemen (contact
      method) had arithmetic mean exposures greater than 100 W.m-1. Of the total
      variance in the logarithms of the weekly magnetic and electric field means, job
      category explained 49.6% and 59.5%, respectively.

PMID- 9000309
TI  - Experts' subjective assessment of pesticide exposure in fruit growing.
AB  - OBJECTIVES: Exposure to pesticides in fruit growing was estimated by pesticide
      experts, occupational hygienists, and fruit growing experts to determine whether
      valid subjective assessments can be made by experts. The study objectives were
      (i) validation of exposure assessment by experts using different sources of
      information, (ii) assessment of interrater agreement, (iii) measurement of
      agreement between experts' assessments and actual quantitative exposure data.
      METHODS: Three groups with different expertise made four ratings. Three of the
      ratings were made in three phases in which exposure information was provided.
      RESULTS: The intraclass correlation was high for each subgroup of experts when
      tasks in fruit growing were relatively ranked by increasing exposure level. In
      general, the interrater agreement on factors influencing the internal dose
      decreased when more information on exposure was provided. Experts correctly
      considered dermal exposure as the prominent contributor to internal dose. Results
      were comparable for the three pesticides under study. The ranking of 15 specific
      sprayings with a fungicide clearly showed differences between raters according to
      their expertise. The pesticide experts and occupational hygienists were able to
      rank daily exposure levels during pesticide spraying in a meaningful way.
      CONCLUSIONS: Experts seem to recognize the most important determinants of
      external exposure and therefore should be able pay a role in evaluating the
      effectiveness of control measures taken to reduce external exposure and to
      determine exposure groups in epidemiologic studies. The expert panel should not
      be too small, and consensus or average estimates should be used because
      differences within expert groups can be considerable.

PMID- 9000310
TI  - Spina bifida and parental occupation in a Swedish register-based study.
AB  - OBJECTIVES: To gather more evidence on a possible relation between spina bifida
      and agricultural and other occupations of parents, a register-based linkage study
      was conducted in Sweden. METHODS: Four hundred and eighty-two cases of spina
      bifida in infants born between 1976 and 1991 were identified from the Swedish
      Register of Congenital Malformations. Nine hundred and sixty-four referents
      without spina bifida were selected from the Medical Birth Register and matched
      for year of birth of the child, maternal age, and parity. Information on
      occupation was obtained from the Medical Birth Register from 1983 on, and from
      the census, which is performed every fifth year. RESULTS: A slightly increased
      odds ratio (OR) was observed for women in agricultural occupations [OR 1.8, 95%
      confidence interval (95% CI) 0.8-4.2]. For all women who had an agricultural
      occupation or lived on a farm, the OR was 2.2 (95% CI 1.3-3.8). The OR values of
      most of the other occupational groups were close to unity. CONCLUSIONS: The
      results suggest an increased risk of spina bifida for the infants of women in
      agricultural occupations, but they do not provide insight into any specific
      occupational risk factors.

PMID- 9000311
TI  - Transient increase in DNA strand breaks in car refinishing spray painters.
AB  - OBJECTIVES: Genotoxic risk was evaluated for spray painters possibly exposed to
      polyester resins and acrylic enamel-based paints in automotive body repair shops.
      METHODS: DNA (deoxyribonucleic acid) strand breaks and alkali-labile sites were
      measured in peripheral mononuclear blood cells ex vivo using the alkaline elution
      method. Samples of venous blood were taken on Monday after a free weekend and
      again on Friday from 38 male and 1 female spray painters and compared with the
      blood samples from 36 male and 3 female referents. The elution rate of each DNA
      sample was standardized by dividing it by the elution rate obtained from
      simultaneously sampled untreated Chinese hamster V79 cells. RESULTS: The spray
      painters showed a significantly (P < 0.001) higher mean level of strand breaks
      and alkali-labile sites in the Friday samples [2.05 (SE 0.17)] compared with the
      Monday samples [1.38 (SE 0.07)]. The Monday results of the spray painters were
      not distinguishable from the referents' [1.41 (SE 0.10)]. The increase in DNA
      damage was numerically higher, but only weakly significant (use of masks, P <
      0.05) or nonsignificant (use of spray booths), when fewer safety provisions were
      taken. CONCLUSIONS: A significant increase in DNA strand breaks and alkali-labile
      sites was found in spray painters after a week's work. However, DNA damage seems
      to be reversible. The use of modern safety equipment seems to affect DNA damage
      only marginally. There is an urgent need to identify the genotoxic chemicals in
      the occupational environment of spray painters and to develop corresponding
      satisfactory safety measures.

PMID- 9000312
TI  - Incidence of lung cancer among cobalt-exposed women.
AB  - OBJECTIVES: The purpose of this study was to estimate the risk of lung cancer for
      women occupationally exposed to cobalt-aluminate spinel. METHODS: A retrospective
      cohort of 874 women occupationally exposed to cobalt in two Danish porcelain
      factories and 520 women not exposed to cobalt were identified from personnel
      files. Vital status was assessed in the national population register, and
      incident cancer cases were traced in the national cancer register. Thirteen women
      (0.92%) were lost to follow-up. The observed deaths and incident cancer cases
      were compared with the expected number based on rates for all Danish women.
      RESULTS: The total mortality of the cohort was the same as for all Danish women.
      The incidence of all cancer was slightly elevated among the exposed women (67
      observed, 55.8 expected) and equal to the expected in the reference group (60
      observed, 60.6 expected). An increased lung cancer incidence was found both in
      the exposed group [8 cases, standardized incidence rate (SIR) 2.35, 95%
      confidence interval (95% CI) 1.01-4.6] and in the reference group (7 cases, SIR
      1.99, 95% CI 0.8-4.1). The exposed group had a relative risk ratio of 1.2 (95% CI
      0.4-3.8) when compared with the reference group. CONCLUSIONS: Both the cobalt
      exposed group and the reference group had an increased lung cancer risk compared
      with all Danish women, but the risk was only slightly higher for the exposed
      group than for the reference group. The study was based on few persons, and we
      recommend a follow-up after five years.

PMID- 9000313
TI  - Bronchial asthma and air pollution at workplaces.
AB  - OBJECTIVES: This case-referent study was performed to investigate the possibility
      of nonspecific air pollution at workplaces increasing the risk of bronchial
      asthma for formerly healthy adults. METHODS: Seventy-nine cases of asthma,
      diagnosed at a lung clinic, among persons aged 20-65 years were compared with 304
      referents drawn randomly from the population of the catchment area. Questionnaire
      information was obtained regarding occupation, exposure to suspect allergens,
      place of residence, smoking habits, and atopy. The subjects' occupations were
      categorized into four air pollution classes based on how the referents reported
      air pollution in their respective occupations. RESULTS: Three years or more of
      work in air-polluted occupations resulted in an odds ratio of 3.0 (OR) (95%
      confidence interval 1.5-6.1) in a comparison with work in occupations with slight
      or no air pollution. Stratification of the material for smoking habits or atopy
      did not alter the results. Nor did the exclusion of specific exposures to
      asthmatogenic agents such as ioscyanates, stainless steel welding, or aluminum
      salts change the effects of the nonspecific air pollution at workplaces. Smoking
      per se was associated with an almost doubled risk for asthma (OR 1.9, 95%
      confidence interval 1.1-3.4). CONCLUSION: The results of this study support an
      association between occupational exposure to nonspecific air pollution and the
      development of bronchial asthma.

PMID- 9000314
TI  - Provocation of the electromagnetic distress syndrome.
AB  - BACKGROUND: Many patients in Sweden are today distressed by fears of "electric
      fields." This phenomenon was almost unknown to occupational health clinics 10
      years ago. CASE HISTORY AND EXAMINATION: A 35-year-old male plumber complained of
      fatigue, headache, lack of concentration, numbness and paresthesia in his arms,
      and a greasy feeling in his palms, where he observed tiny shiny spots. These
      symptoms made him unable to work. It all started after a period of high strain at
      the work. He feared negative influences, mainly from electric fields. Signs
      indicating nerve entrapment in the upper extremities were found in a clinical
      examination. PROVOCATION STUDY: The patient was blindly provocated in a whole
      body electromagnetic coil at 34 or 100 microT randomly mixed with sham exposures.
      After being blinded against irrelevant external cues, he was not able to detect
      the existence of or any symptoms at either field intensity. He was informed about
      the results and was later able to return to his previous work. CONCLUSIONS: No
      sensitivity to electromagnetic fields could be objectively verified for this
      patient, who was suspected to suffer from a thoracic outlet syndrome.

PMID- 9000315
TI  - Cerebral lateralization is delayed in children who later develop schizophrenia.
AB  - The origins of schizophrenia are obscure. One suggestion is that it represents a
      component of the genetic variation associated with the establishment of dominance
      in one or other cerebral hemisphere, a mechanism that has been crucial in the
      evolution of language. Indices of cerebral hemispheric dominance (hand, foot and
      eye preference, speed of checking squares) recorded on the 16,980 children in the
      UK National Child Development Study cohort were examined in relation to
      psychiatric admission by the age of 28 years. Diagnoses were established by the
      application of Present State Examination criteria to case notes. Pre
      schizophrenic children (n = 34-36) were more likely (p < 0.0003) to be rated by
      their mothers as ambidextrous at the age of 7 years, and at 11 years were less (p
      < 0.01) strongly right-handed than their peers in the cohort population on a test
      of relative hand skill: children who later developed affective psychosis (n = 25)
      or neurosis (n = 60) did not differ significantly from controls. Delay in
      establishing dominance in one hemisphere could be the critical factor that
      predisposes to schizophrenia.

PMID- 9000316
TI  - The Stroop effect in schizophrenic patients.
AB  - Schizophrenic patients (n = 44) and normal controls (n = 50) performed a
      computerized version of the Stroop color-word interference task. Schizophrenic
      patients generally showed more Stroop interference than normal subjects. The
      effect was neither related to demographic variables, nor to actual
      psychopathology. However, the course of the disorder was related to the Stroop
      effect, in that acute, chronic, and schizoaffective patients displayed a larger
      interference effect than patients with a recurrent episode. From a methodological
      perspective, the computerized version of the Stroop task proved to be more
      sensitive to interference effects in the patient group. The finding of enhanced
      reverse Stroop interference in patients strongly preoccupied with colors is
      discussed within the framework of MacLeod and Dunbar's (MacLeod and Dunbar, 1988)
      theory of Stroop interference involving differential practice effects.

PMID- 9000317
TI  - Meta-analysis of brain and cranial size in schizophrenia.
AB  - Several meta-analyses are presented that address the issue of brain and/or
      cranial size reductions in schizophrenia. Separate meta-analyses were conducted
      for brain size (n = 27 studies), intracranial size (n = 18) or extracranial size
      (n = 8). For each meta-analysis, the weighted composite effect size (d) was
      tested for statistical significance (the direction of the effect size was
      negative if patients with schizophrenia had smaller structure size than
      controls). The influence of several potential modifiers of effect size (age,
      methods, region, gender) was individually evaluated. The composite effect sizes
      for studies of brain, intracranial and extracranial measures were d = -0.26, (p <
      0.0001), d = -0.18, (p = 0.0012), and d = +0.14, (p = 0.16), respectively. Thus,
      the review found evidence for a small, but statistically significant reduction in
      brain and intracranial size in schizophrenia, but no evidence for a reduction in
      extracranial size. Studies based on axial image slices had significantly larger
      effects (d = -0.60) than the studies based on sagittal images (d = -0.09) (chi(2)
      = 14.0, p = 0.0002). In summary, the findings clearly support a small yet highly
      significant reduction of brain and intracranial size in schizophrenia.

PMID- 9000318
TI  - Lack of gender differences in neuroleptic response in patients with
      schizophrenia.
AB  - OBJECTIVE: The authors sought to determine if there were gender differences in
      neuroleptic response in male and female patients with schizophrenia who were
      matched for clinical and demographic variables and participated in a double-blind
      trial of traditional antipsychotic drugs. METHODS: 24 males (m) and 20 females
      (f) with schizophrenia or schizoaffective disorder who did not differ in clinical
      characteristics (age of onset, course of illness, prior hospitalizations,
      premorbid functioning) participated in an extended drug-free period followed by a
      neuroleptic trial under double-blind, placebo-controlled conditions. RESULTS:
      Males and females showed significant improvement in total, positive and negative
      BPRS symptoms during neuroleptic treatment. However, there were no significant
      differences in treatment response between sexes. No sex differences were found in
      baseline drug-free symptomatology, neuroleptic dose or dosage by weight.
      CONCLUSIONS: There were no significant sex differences in neuroleptic treatment
      response in male and female patients well-matched for clinical, treatment and
      demographic characteristics. Methodological issues which distinguish this study
      from prior studies reporting gender differences in neuroleptic response are
      examined.

PMID- 9000320
TI  - Factor analysis of schizophrenic symptoms using the OPCRIT checklist.
AB  - Factor analysis was performed on OPCRIT checklist psychotic symptoms rated on 102
      patients with DSM-III-R schizophrenia. An initial three-factor solution produced
      positive, negative, and disorganisation factors. However, application of the
      scree test suggested five substantive factors, with the positive factor dividing
      into three factors characterised, respectively, by paranoid symptoms, first rank
      delusions and first rank hallucinations.

PMID- 9000319
TI  - Cognitive impairment and negative symptoms in geriatric chronic schizophrenic
      patients: a follow-up study.
AB  - Cognitive impairment is increasingly recognized as an important aspect of
      schizophrenia. Since cognitive impairment has many features in common with the
      negative symptoms of the illness, it is possible that some of the characteristics
      attributed to negative symptoms are due to an association with cognitive
      impairments. In order to test this hypothesis, 174 chronically hospitalized
      geriatric schizophrenic patients were examined twice at a 1-year follow-up with
      ratings of the severity of their symptoms (using the Positive and Negative
      Syndrome Scale: PANSS) and assessments of cognitive functions with the Mini
      Mental State Examination and a brief neuropsychological battery aimed at the
      typical impairments seen in dementia. Positive symptoms were unassociated with
      any of the cognitive variables, while negative symptom severity was correlated
      with each of the cognitive measures. In the cross-temporal analyses, cognitive
      impairments were more stable over time than negative symptom scores, but
      cognitive impairment did not predict the severity of any negative symptom over
      time. At each assessment, however, cognitive impairment was strongly correlated
      with each of the seven negative symptoms studied. These data indicate that
      cognitive impairments and negative symptoms are related, but discriminable,
      features in schizophrenia and that the considerable overlap between some negative
      symptoms and estimates of cognitive function may suggest a rethinking of the
      definition of some of these symptoms.

PMID- 9000321
TI  - Implicit and explicit associative memory in patients with schizophrenia.
AB  - Control and Schizophrenic subjects performed memory tests under conditions in
      which performance is influenced by newly acquired information about associations
      between pairs of normatively unrelated words (a 'context' word and a target
      word). In Experiment 1, the associative memory test was implicit. Control and
      schizophrenic subjects reached the same level of performance and, more
      importantly, both groups used contextual information to the same extent. In
      Experiment 2, subjects were submitted to an explicit and an implicit memory test
      in succession. Overall performance of schizophrenic patients was impaired in the
      explicit memory test. But, as in Experiment 1, the two groups did not differ in
      the overall level of implicit memory, and context improved performance to the
      same extent in both tests. These results run counter to the widespread idea that
      schizophrenic patients exhibit a deficit in processing all types of contexts, and
      suggest that the deficit may be limited to the processing of what Baddeley (1982)
      calls 'interactive' context.

PMID- 9000322
TI  - Effect of clozapine on physical and verbal aggression.
AB  - OBJECTIVE: The hypothesis that clozapine reduced serious physically and verbally
      aggressive behavior of persons with schizophrenia whose symptoms did not respond
      to typical neuroleptic treatment was tested. METHOD: Incident reports of
      aggression and restraint of 75 such inpatients were reviewed for 3 months before
      clozapine treatment and for 6 months of clozapine treatment. BPRS scores were
      also examined. Twenty-eight patients with no incidents were removed from study.
      RESULTS: There were significantly fewer incidents of physical aggression per
      month per patient on clozapine than before clozapine (mean +/- S.D. = 0.13 +/-
      0.25 vs. 0.54 +/- 0.93; t = 3.4, df = 46, p < 0.002) and a similar decline in
      verbal aggression (0.21 +/- 0.31 vs. 0.73 +/- 0.83; t = 4.3, df = 46, p < 0.000).
      On clozapine, 49% (n = 23) of patients had fewer incidents of physical
      aggression, 36% (n = 17) showed no change and 15% (n = 7) showed more. Seventy
      percent (n = 33) of patients had fewer incidents of verbal aggression, 4% (n = 2)
      showed no change and 25% (n = 12) had more. During the 3 months before clozapine,
      14 patients (30%) were restrained a total of 40 times. During the first 6 months
      of clozapine treatment, three patients (6%) were restrained a total of six times.
      There were significant decreases in BPRS hostility, positive, negative and
      psychosis scores. CONCLUSION: Clozapine appears to reduce serious aggression
      among some patients.

PMID- 9000324
TI  - Risperidone-reserpine combination in refractory psychosis.

PMID- 9000323
TI  - Insight in first-admission psychotic patients.
AB  - BACKGROUND: The prevalence of insight was examined longitudinally in psychotic
      patients with schizophrenia (n = 86), bipolar disorder (n = 52), major depressive
      disorder (n = 35) and other psychoses (n = 16). METHOD: Before discharge and at 6
      month follow-up, insight in first-admission patients from 10 facilities in
      Suffolk County, New York was rated as part of a modified Hamilton Depression
      Scale. RESULTS: Initially, 80% of depressives but approximately half with other
      diagnoses manifested insight. At follow-up, most patients demonstrated insight
      except for the schizophrenic patients. After controlling for diagnosis,
      significant correlates of baseline insight were being married, hospitalized in a
      community or academic facility, intelligence and negative symptoms. At follow-up,
      after controlling for diagnosis and baseline insight, prior treatment was
      predictive. This finding held for schizophrenic patients separately. CONCLUSION:
      Lack of insight is more prevalent in schizophrenia and improves over time. The
      components of prior treatment leading to better insight should be explored.

PMID- 9000325
TI  - Intra-alveolar transplantation. I. A 10-year follow-up of a method for surgical
      extrusion of root fractured teeth.
AB  - A group of 19 patients where traumatic root fractures were treated with surgical
      extrusion procedure has been clinically and radiographically followed up for 10
      years. Except for one out of 21 intraalveolar transplanted roots all functioned
      with different kinds of crown restorations and without pathological
      complications. The surgical extrusion method should thus be a useful tool in the
      treatment of teeth with cervical root-fractures and also teeth with deep cervical
      root caries which are difficult to treat conservatively.

PMID- 9000326
TI  - Dental clinics--a burden to environment?
AB  - To estimate environmental burden of mercury from dental clinics, a survey was
      conducted in 1993 at dental clinics in northern part of Sweden. Factors regarding
      amalgam separators, maintenance and disposal of collected sludge, age of clinics,
      cleaning of waste pipes, and sorting and handling of amalgam contaminated
      products were investigated. The result showed that many were not familiar with
      maintenance of the amalgam separator. A majority, 68%, were working in clinics
      older than 10 years, but only 9% reported that waste pipes had been cleaned or
      changed. Classification of amalgam contaminated products as high-risk and low
      risk waste differed a lot, as well as handling of waste products. The result
      shows that there is need for more information and attention to all individuals
      working in Dental Care on how to reduce environmental burden of mercury from
      dental clinics.

PMID- 9000327
TI  - Dental appliances in the treatment of snoring. A comparison between an activator,
      a soft-palate lifter, and a mouth-shield.
AB  - Different dental appliances have been recommended in the treatment of snoring.
      The aim of the present study was to compare three different dental appliances
      regarding patient tolerance and the effect of snoring. Fifteen consecutive
      snorers were randomly selected to treatment with either a mandibular advancement
      device (activator), a soft-palate lifter or a mouth-shield. The activator
      satisfactorily reduced snoring in four out of five patients. At four-year follow
      up, two patients had discontinued the treatment, one due to craniomandibular
      disorder. The soft-palate lifter had insufficient effect on snoring in four out
      of five patients. The results suggest that the activator has a satisfactory
      tolerance and effect on snoring, while the soft-palate lifter and the mouth
      shield are ineffective in the treatment of snoring.

PMID- 9000328
TI  - A longitudinal study of dental health in a group of Swedish teenagers/young
      adults from the age of 14 to 25.
AB  - 87 participants were followed from the ages of 14 to 25. Data concerning dental
      caries, gingival status, pocket depth, subgingival calculus, loss of attachment,
      and regularity of dental care were recorded. During the 11-yr-study-period 16% of
      the participants did not develop any carious lesions at all, and the average
      increase in DMFS-value was 0.6 per year. At age 25, about 75% of the subjects had
      never experienced any manifest carious lesions in incisors or cuspids or on any
      buccal and lingual surfaces, and 30% had never needed any proximal restorations.
      Over the study period, gingival inflammation changed from being merely a result
      of poor oral hygiene to being an indication of initial periodontal disease, and
      at age 25, 11% showed evidence of loss of marginal bone. The Dental Health was
      better in females than in males. In general, this sex differences increased in
      age, and at the age of 19 it had become clinically significant. The good habit of
      regular dental care reinforced during these 19 years of life was continued by 91%
      at 25, and no difference could be seen between the care rendered by the Public
      Dental Health Care system and by Private General Practitioners.

PMID- 9000329
TI  - Salivary factors in children with recurrent parotitis. Part 2: Protein, albumin,
      amylase, IgA, lactoferrin lysozyme and kallikrein concentrations.
AB  - The concentrations of total protein, albumin, amylase, IgA, lactoferrin, lysozyme
      and kallikrein in parotid saliva from 17 children with juvenile recurrent
      parotitis (JRP) in a non-active phase of disease and in healthy controls of the
      same number, sex and age were analysed after gustatory stimulation with 1%, 2%
      and 6% citric acid. There was a great individual variation in all analysed
      variables, especially in saliva from the diseased glands. Significantly raised
      levels of albumin, IgA, lactoferrin and kallikrein were found in the saliva from
      the JRP-children compared with the controls (p < 0.01-0.001), while total protein
      and alpha-amylase did not differ significantly. The sialo-chemical findings are
      discussed in the light of histological and bacteriological findings and support
      the hypothesis that the etiology of juvenile recurrent parotitis is a combination
      of congenital malformation of portions of the salivary ducts and a set-in
      infection.

PMID- 9000330
TI  - Modulation by fish oil diet of eicosanoid-induced anion secretion in the rat
      distal colon.
AB  - Eicosanoids are involved in the mediation of inflammatory and allergic processes
      in the gut. In order to evaluate a potential beneficial effect of the diet, the
      effect of mediators of inflammation and of a sensitization against egg albumin on
      anion secretion across the colon was tested using rats fed on a diet containing
      15% fish oil as compared to 15% olive oil as donor animals. Feeding on a fish oil
      diet significantly reduced the response to bradykinin or phospholipase C, known
      agonist of prostaglandin-induced secretion, by about 50%. The increase in short
      circuit current (Isc) induced by the phospholipase A2 stimulator, melittin, or by
      distension of the gut wall were only insignificantly inhibited by 15-30%.
      Administration of egg albumin to the mucosas from animals sensitized against egg
      albumin induced an indomethacin- and tetrodotoxin-sensitive increase in Isc. This
      response was, however, only insignificantly (30%) reduced by the fish oil diet.
      In conclusion, the effect of fish oil diet depends on the stimulus used for
      activation of prostaglandin release. This suggested that different pools of
      arachidonic acid are differentially affected by the diet or that certain stimuli
      for phospholipases are strong enough to overcome the effect of a reduced
      substrate availability. Consequently, a diet rich in polyunsaturated n-3 fatty
      acids may only play an adjuvant role for the therapy of inflammatory or allergic
      intestinal diseases.

PMID- 9000331
TI  - A study on the nutritive value of pollen from the Chinese Masson Pine (Pinus
      massoniana) and its effect on fecal characteristics in rats.
AB  - A digestion experiment with growing rats was conducted to study the effect of
      native and broken pollen of Chinese Masson Pine (Pinus massoniana) on fecal
      composition and digestibilities of dry matter, crude protein and crude ash. For
      that issue each 10 of 30 animals were fed a semisynthetic diet containing either
      no pollen or and addition of 6% native or broken pollen for 17 days at restricted
      amounts. In a second experiment each 6 of 12 growing rats received a
      semisynthetic diet containing either no or 5% broken pollen. At day 4, 11 and 18
      samples of the feces were collected and analyzed for mesophilic aerobic bacteria.
      The pollen contained large amounts of cell wall constituents (26-30% lignin and
      10-15% cellulose, 2-13% hemicellulose) with higher values found in native pollen.
      The contents of crude protein, crude fat, total lipids, available carbohydrates
      (starch and sugars), crude ash, gross energy and metabolizable energy were 13%, 2
      10%, 8-10%, 17-18%, 3.1-3.5%, 21-22 kJ/g and 5.7-9.0 kJ/g. The addition of native
      pollen to the diet increased the total amount of feces by 71% as compared to the
      control level. The fecal contents of dry matter and of crude protein and crude
      ash in fecal dry matter changed by -5, +4 and -5 percentage units. The apparent
      digestibilites of dry matter and crude protein decreased by 3 and 5 percentage
      units, respectively, while the apparent digestibility of crude ash remained
      unchanged. Broken pollen acted in the same direction, however the effects were
      about 20% less pronounced as compared to native pollen. The pollen feeding
      reduced the fecal germ contents of Proteus mirabilis and Escherichia coli, while
      the amounts of alpha-hemolysing streptococci was increased. In total, the
      observed effects of an addition of native broken or pollen to the diet seemed to
      be based mainly on the increased intake of cell wall constituents.

PMID- 9000334
TI  - Differential cytochrome content and reductase activity in Geospirillum barnesii
      strain SeS3
AB  - The protein composition, cytochrome content, and reductase activity in the
      dissimilatory selenate-reducing bacterium Geospirillum barnesii strain SeS3,
      grown with thiosulfate, nitrate, selenate, or fumarate as the terminal electron
      acceptor, was investigated. Comparison of seven high-molecular-mass membrane
      proteins (105.3, 90.3, 82.6, 70.2, 67.4, 61.1, and 57.3 kDa) by SDS-PAGE showed
      that their detection was dependent on the terminal electron acceptor used.
      Membrane fractions from cells grown on thiosulfate contained a 70.2-kDa c-type
      cytochrome with absorbance maxima at 552, 522, and 421 nm. A 61.1-kDa c-type
      cytochrome with absorption maxima at 552, 523, and 423 nm was seen in membrane
      fractions from cells grown on nitrate. No c-type cytochromes were detected in
      membrane fractions of either selenate- or fumarate-grown cells. Difference
      spectra, however, revealed the presence of a cytochrome b554 (absorption maxima
      at 554, 523, and 422 nm) in membrane fractions from selenate-grown cells and a
      cytochrome b556 (absorption maxima at 556, 520, and 416 nm) in membrane fractions
      from fumarate-grown cells. Analysis of reductase activity in the different
      membrane fractions showed variability in substrate specificity. However, enzyme
      activity was greatest for the substrate on which the cells had been grown (e.g.,
      membranes from nitrate-grown cells exhibited the greatest activity with nitrate).
      These results show that protein composition, cytochrome content, and reductase
      activity are dependent on the terminal electron acceptor used for growth.

PMID- 9000332
TI  - IgE binding to a new cross-reactive structure: a 35 kDa protein in birch pollen,
      exotic fruit and other plant foods.
AB  - Food allergies in birch pollen allergic patients have been shown to be due to
      cross-reactivities of specific IgE antibodies which are directed against birch
      pollen allergens with related proteins in fruit, nuts and vegetables. We
      identified a new cross-reactive structure of 35 kDa in birch pollen and some
      plant food extracts by Enzyme Allergosorbent Test (EAST) and immunoblot
      inhibition studies. The 35 kDa birch pollen protein is a minor allergen to which
      approximately 10-15% of birch pollen allergic individuals have specific IgE. Our
      data demonstrate that there is cross-reactivity of this protein with proteins of
      comparable size from lychee, mango, banana, orange, apple, pear and carrot. While
      the 35 kDa protein is immunologically independent of the major birch pollen
      allergen Bet v 1, we also observed IgE binding to a 34 kDa structure which
      appears to be a Bet v 1 dimer.

PMID- 9000333
TI  - Breakfasts with different fiber and macronutrient contents do not differentially
      affect timing, size or microstructure of the subsequent lunch.
AB  - The effects of four equienergetic breakfasts with varying fiber and macronutrient
      contents on hunger and satiety ratings, on subsequent lunch intake, and on
      postprandial carbohydrate and fat metabolism were investigated in normal weight
      male subjects in two experiments, in which lunch was offered at a predetermined
      time (Experiment 1) or in which the subjects were free to choose when to eat
      lunch (Experiment 2). Consumption of either a commercially available high fiber
      cereal (HFC, 10% fiber), a medium fiber cereal (MFC, 7% fiber), a low fiber
      cereal (LFC, 3% fiber), or a standard continental breakfast (0% fiber) on
      nonconsecutive days did not differentially affect hunger and satiety ratings, the
      size or microstructure of the subsequent lunch, and the breakfast to lunch
      intermeal interval (in Experiment 2). Plasma concentrations of glucose, lactate,
      and insulin increased more after the LFC breakfast than after the other breakfast
      varieties. A reactive postprandial hypoglycaemia occurred after the LFC
      breakfast, shortly before lunch. The plasma concentrations of fat metabolites
      (triglycerides, free fatty acids, beta-hydroxybutyrate) and of glucagon were not
      differentially affected by the breakfast varieties. The results are consistent
      with the assumption that energy content of a meal is the major determinant of
      subsequent energy intake in man and the fiber content and macronutrient
      composition have only a modulating effect.

PMID- 9000335
TI  - Respiratory stimulation and generation of superoxide radicals in Pseudomonas
      aeruginosa by fungal naphthoquinones.
AB  - The mechanism of action of antimicrobial naphthoquinones from the fungus Fusarium
      was studied by using Pseudomonas aeruginosa. Bostricoidin, methyl ether
      fusarubin, and fusarubin stimulated the oxygen consumption of bacterial cells and
      induced cyanide-insensitive oxygen consumption. These activities of the tested
      compounds were also observed in bacterial membrane preparations in a dose
      dependent manner. Naphthoquinones stimulated the generation of superoxide anion
      and hydrogen peroxide. The naphthoquinone effectively acted as the electron
      acceptors for bacterial diaphorase, which could explain the antibacterial
      activity of Fusarium naphthoquinones since electron acceptors lead to the
      stimulation of respiratory activity and the generation of oxygen radical species.

PMID- 9000336
TI  - Chromatium glycolicum sp. nov., a moderately halophilic purple sulfur bacterium
      that uses glycolate as substrate
AB  - From the microbial mats that develop in Solar Lake, a new purple sulfur bacterium
      was isolated. This strain (Chromatium strain SL 3201) was morphologically similar
      to Chromatium gracile and Chromatium minutissimum. Chromatium SL 3201 was found
      to be a moderate halophile with a growth range between 2 and 20% NaCl (optimum 4
      5% NaCl) and was able to grow photo-organotrophically using glycolate and
      glycerol. It is the first described phototrophic sulfur bacterium able to use
      glycolate. According to NaCl requirements and utilization of organic compounds,
      the strain is not related to any known species of the genus Chromatium. On the
      basis of its 16S rRNA gene sequence, it clusters with other Chromatium species
      and is most similar to Chromatium salexigens and Chr. gracile, but it is
      sufficiently separated to be considered as a new species of the genus. It is,
      therefore, described as Chromatium glycolicum sp. nov.

PMID- 9000337
TI  - Pathways of autotrophic CO2 fixation and of dissimilatory nitrate reduction to
      N2O in Ferroglobus placidus
AB  - The strictly anaerobic Archaeon Ferroglobus placidus was grown
      chemolithoautotrophically on H2 and nitrate and analyzed for enzymes and
      coenzymes possibly involved in autotrophic CO2 fixation. The following enzymes
      were found [values in parentheses = MUmol min-1 (mg protein)-1]:
      formylmethanofuran dehydrogenase (0.2),
      formylmethanofuran:tetrahydromethanopterin formyltransferase (0.6),
      methenyltetrahydromethanopterin cyclohydrolase (10), F420-dependent
      methylenetetrahydromethanopterin dehydrogenase (1.5), F420-dependent
      methylenetetrahydromethanopterin reductase (0.4), and carbon monoxide
      dehydrogenase (0.1). The cells contained coenzyme F420 (0.4 nmol/mg protein),
      tetrahydromethanopterin (0.9 nmol/ mg protein), and cytochrome b (4 nmol/mg
      membrane protein). From the enzyme and coenzyme composition of the cells, we
      deduced that autotrophic CO2 fixation in F. placidus proceeds via the carbon
      monoxide dehydrogenase pathway as in autotrophically growing Archaeoglobus and
      Methanoarchaea species. Evidence is also presented that cell extracts of F.
      placidus catalyze the reduction of two molecules of nitrite to 1 N2O with NO as
      intermediate (0.1 MUmol N2O formed per min and mg protein), showing that - at
      least in principle - F. placidus has a denitrifying capacity.

PMID- 9000338
TI  - Haem O and a putative cytochrome bo in a mutant of Bacillus cereus impaired in
      the synthesis of haem A.
AB  - In a spontaneous mutant (PYM1) of Bacillus cereus impaired in the synthesis of
      haem A, no haem-A-containing cytochromes were detected spectroscopically. The
      haem A deficiency was compensated by high levels of haem O and a CO-reactive
      cytochrome o in membranes; no other oxidases were detected. In contrast, the wild
      type strain had considerable amounts of haem A and negligible levels of haem O.
      The mutant PYM1 exhibited normal colony morphology, growth, and sporulation in
      nonfermentable media, whereas on fermentable media, the mutant overproduced acid,
      which led to poor growth and inhibition of sporulation. External control of the
      pH of the medium in fermentable media allowed close-to-normal growth and massive
      sporulation of the mutant. The presence of membrane-bound cytochrome caa3-OII and
      aa3-II subunits in strain PYM1 was confirmed by Western blots and haem C staining
      (COII subunit). Western blotting also revealed that in contrast to the wild-type 
      strain PYM1 contained the membrane-bound subunits caa3-COI and aa3-I, but in low
      amounts. The effect of several respiratory inhibitors on the respiratory system
      of strain PYM1 suggested that the terminal oxidase is highly resistant to KCN and
      CO and that a c-type cytochrome might be involved in the electron transfer
      sequence to the putative cytochrome bo.

PMID- 9000339
TI  - Biotransformation of 1-naphthalenesulfonic acid by the green alga Scenedesmus
      obliquus.
AB  - Under sulfate limitation, axenic batch cultures of the green alga Scenedesmus
      obliquus metabolized 1-naphthalenesulfonic acid and partially used the sulfonate
      as a source of sulfur. The main metabolite, 1-hydroxy-2-naphthalenesulfonic acid,
      which was not metabolized further in the algal culture, was formed by
      hydroxylation of the substrate in position 1 and by migration of the sulfonic
      acid group to position 2 of the naphthalene ring (NIH shift). A smaller amount of
      1-naphthalenesulfonic acid was desulfonated. The resulting 1-naphthol was mostly
      transformed into 1-naphthyl beta-d-glucopyranoside.

PMID- 9000340
TI  - Physiological characteristics and growth behavior of single and double
      hydrogenase mutants of Desulfovibrio fructosovorans.
AB  - The presence of one periplasmic [NiFe] hydrogenase, one periplasmic [Fe]
      hydrogenase, and one cytoplasmic NADP-reducing hydrogenase has been previously
      established in Desulfovibrio fructosovorans. In the present work, marker-exchange
      mutagenesis was performed to determine the function of the tetrameric NADP
      reducing hydrogenase encoded by the hndA, B, C, and D genes. The mutations
      performed were not lethal to the cells, although the H2-dependent NADP reduction
      was completely abolished. The double-mutated DM4 (DeltahynABC, DeltahndD) strain
      was still able to grow on hydrogen plus sulfate as the sole energy source. The
      growth may have occurred under these culture conditions because of the presence
      of the remaining [Fe] hydrogenase. The cells grew differently on various
      substrates depending on whether fructose, lactate, or pyruvate was used in the
      presence of sulfate. The (hnd mutant growth rates were 25-70% lower than those of
      the wild-type strain, although the molar growth yield remained unchanged. By
      contrast, mutants devoid of both [NiFe] hydrogenase and NADP-reducing hydrogenase
      had 24-38% lower growth yields and showed a corresponding drop in the growth
      rates. We concluded that each of the three hydrogenases may contribute to the
      energy supply in D. fructosovorans and that the loss of one enzyme might be
      compensated for by another. However, the loss of two hydrogenases affected the
      phosphorylation accompanying the metabolism of fructose, lactate, and pyruvate.

PMID- 9000341
TI  - Methylosulfonomonas methylovora gen. nov., sp. nov., and Marinosulfonomonas
      methylotropha gen. nov., sp. nov.: novel methylotrophs able to grow on
      methanesulfonic acid.
AB  - Two novel genera of restricted facultative methylotrophs are described; both
      Methylosulfonomonas and Marinosulfonomonas are unique in being able to grow on
      methanesulfonic acid as their sole source of carbon and energy. Five identical
      strains of Methylosulfonomonas were isolated from diverse soil samples in England
      and were shown to differ in their morphology, physiology, DNA base composition,
      molecular genetics, and 16S rDNA sequences from the two marine strains of
      Marinosulfonomonas, which were isolated from British coastal waters. The marine
      strains were almost indistinguishable from each other and are considered to be
      strains of one species. Type species of each genus have been identified and named
      Methylosulfonomonas methylovora (strain M2) and Marinosulfonomonas methylotropha
      (strain PSCH4). Phylogenetic analysis using 16S rDNA sequencing places both
      genera in the alpha-Proteobacteria. Methylosulfonomonas is a discrete lineage
      within the alpha-2 subgroup and is not related closely to any other known
      bacterial genus. The Marinosulfonomonas strains form a monophyletic cluster in
      the alpha-3 subgroup of the Proteobacteria with Roseobacter spp. and some other
      partially characterized marine bacteria, but they are distinct from these at the
      genus level. This work shows that the isolation of bacteria with a unique
      biochemical character, the ability to grow on methanesulfonic acid as energy and
      carbon substrate, has resulted in the identification of two novel genera of
      methylotrophs that are unrelated to any other extant methylotroph genera.

PMID- 9000343
TI  - Identification of an assimilatory nitrate reductase in mutants of Paracoccus
      denitrificans GB17 deficient in nitrate respiration
AB  - A Paracoccus denitrificans strain (M6Omega) unable to use nitrate as a terminal
      electron acceptor was constructed by insertional inactivation of the periplasmic
      and membrane-bound nitrate reductases. The mutant strain was able to grow
      aerobically with nitrate as the sole nitrogen source. It also grew anaerobically
      with nitrate as sole nitrogen source when nitrous oxide was provided as a
      respiratory electron acceptor. These growth characteristics are attributed to the
      presence of a third, assimilatory nitrate reductase. Nitrate reductase activity
      was detectable in intact cells and soluble fractions using nonphysiological
      electron donors. The enzyme activity was not detectable when ammonium was
      included in the growth medium. The results provide an unequivocal demonstration
      that P. denitrificans can express an assimilatory nitrate reductase in addition
      to the well-characterised periplasmic and membrane-bound nitrate reductases.

PMID- 9000342
TI  - Clostridium vincentii sp. nov., a new obligately anaerobic, saccharolytic,
      psychrophilic bacterium isolated from low-salinity pond sediment of the McMurdo
      Ice Shelf, Antarctica.
AB  - A gram-positive, motile, rod-shaped, strictly anaerobic bacterium was isolated
      from an enrichment initiated with sediment taken from below the cyanobacterial
      mat of a low-salinity pond on the McMurdo Ice Shelf, Antarctica. The organism
      grew optimally at 12 degrees C, at pH 6.5, and at an NaCl concentration of< 0.5%
      (w/v). It survived freeze-thawing at low salt concentrations,but not exposure to
      temperatures over 25 degrees C for more than 20 h or short-term exposure to
      temperatures> 50 degrees C. Out of a variety of polysaccharides tested as growth
      substrates, only xylan supported growth. The organism also grew on a variety of
      mono- and disaccharides including the cyanobacterial cell wall constituent, N
      acetyl glucosamine. Fermentation products on a mol product per 100 mol of hexose
      monomer fermented basis were: acetate, 72; formate, 72; butyrate, 55; hydrogen,
      114; and CO2, 100. Not detectable in the culture medium(< 2 mol per 100 mol of
      monomer) were lactate, propionate, ethanol,n-propanol, n-butanol, and succinate.
      The G+C content of the DNA from the bacterium was 33 mol%, and a phylogenetic
      analysis indicated that it grouped closely with members of the RNA-DNA homology
      group 1 of the genus Clostridium. It differed from other species of this genus
      with regard to growth temperature optimum, substrate range, and fermentation
      pattern, and is therefore designated as a new species of Clostridium for which
      the name Clostridium vincentii is proposed. The type strain is lac-1 (DSM 10228).

PMID- 9000344
TI  - NSAIDs and the gastrointestinal tract.

PMID- 9000345
TI  - Solitary ulcers in reflux esophagitis: radiographic findings.
AB  - BACKGROUND: Some patients with reflux esophagitis have solitary ulcers in the
      distal esophagus. This study was undertaken to characterize further the
      radiographic features of these ulcers and to determine whether or not they have a
      predisposition to develop on the posterior esophageal wall. METHODS: Radiologic
      files and teaching files at our university hospital and affiliated Veterans
      Administration hospital revealed 29 patients with solitary reflux-induced ulcers.
      The radiographs were reviewed retrospectively to determine the size and location
      of the ulcers as well as the presence or absence of other findings. RESULTS:
      Twenty ulcers (69%) were located on the posterior wall, five (17%) on the left or
      right lateral wall, and four (14%) on the anterior wall. All but two ulcers were
      located 1-4 cm from the gastroesophageal junction. All of the ulcers were less
      than 10 mm in width and 5 mm in depth. Other associated findings included hiatal
      hernias in 11 patients (38%), mucosal nodularity or granularity in 12 (41%), one
      or more tiny satellite ulcers in three (10%), esophageal intramural
      pseudodiverticula in three (10%), an inflammatory esophagogastric polyp in one
      (3%), and scarring or stricture formation in 12 (41%). CONCLUSION: Our findings
      suggest that solitary reflux-induced ulcers tend to occur on the posterior wall
      of the distal esophagus near the gastroesophageal junction, producing
      characteristic radiographic findings. We postulate that affected individuals
      sleep primarily in the supine position, so that refluxed acid pools on the
      dependent or posterior esophageal wall, causing maximal injury in this location.

PMID- 9000346
TI  - Primary non-Hodgkin's lymphoma of the esophagus.
AB  - The esophagus is the least commonly involved gastrointestinal organ, accounting
      for fewer than 1% of patients with lymphoma. Such involvement is mostly
      secondary, from mediastinal lymph nodes or gastric lymphoma. The primary form
      arises from the esophageal wall itself and occurs much less frequently. Primary
      esophageal lymphoma is mostly seen in male patients with Hodgkin's disease. A
      primary non-Hodgkin's lymphoma of the esophagus with concomitant involvement of
      the bone marrow is presented, and imaging features of esophageal lymphoma are
      reviewed.

PMID- 9000347
TI  - AIDS-related primary esophageal lymphoma.
AB  - AIDS-related primary esophageal lymphoma should be considered in the differential
      diagnosis of a patient with AIDS who presents with dysphagia and a large
      ulcerated esophageal mass. Endoscopy is mandatory in those patients to establish
      a definitive diagnosis and to rule out the possibility of an infectious cause of
      the mass.

PMID- 9000348
TI  - Nonexpandable silicone esophageal stents for treatment of malignant
      tracheoesophageal fistulas: complications and radiographic appearances.
AB  - BACKGROUND: The aim was to evaluate the radiologic appearances and complications
      that occurred after placement of nonexpandable silicone stents used as palliative
      therapy for patients with malignant tracheoesophageal fistulas (TEFs). METHODS:
      Records of 11 patients (6 males, 5 females) who underwent placement of esophageal
      stents for malignant TEF between 1988 and 1994 were reviewed. Nine patients had
      esophageal carcinoma and two patients bronchogenic carcinoma. A TEF was
      documented radiographically in all patients. Silicone stents were placed in all
      patients under endoscopic guidance. A chest radiograph was obtained for each
      patient immediately following stent placement to confirm proper positioning and
      to assess complications. A contrast study was performed within 24 hours after the
      procedure to evaluate the function of the stent and its efficacy for occluding
      the fistulous tract. The patients were followed until January 1995 or until their
      death (range 1.5-24. 0 months). RESULTS: Seven of the patients developed stent
      related complications. Within the first 24 hours after stent insertion (which was
      successful in 100% of cases), 2 of the 11 patients developed minor complications.
      One patient had pooling of contrast around the proximal portion of the stent
      leading to aspiration of contrast, and one patient experienced transient,
      asymptomatic, idiopathic, esophagovenous intravasation. Delayed (>24 hours)
      complications related to stent placement occurred in five of the patients: one
      patient each had pooling at the proximal end of the stent with aspiration,
      worsening esophageal dysphagia causing reflux through the stent, caudad stent
      migration, superior stent migration, epithelial hyperplasia causing obstruction
      of the stent, and pressure necrosis. There were no cases of hemorrhage. Two
      patients were lost to long-term follow-up, and eight patients died of their
      disease, all unrelated to the stent placement. CONCLUSION: Silicone esophageal
      stents provide successful short-term palliation for most patients with malignant
      TEF but are not without associated complications. These complications, however,
      can usually be detected early using radiographic imaging, permitting remediation.

PMID- 9000349
TI  - Thoracic esophageal carcinoma: evaluation in the sagittal section with magnetic
      resonance imaging.
AB  - Among 54 patients with thoracic esophageal carcinoma (53 squamous cell carcinoma,
      1 adenosquamous carcinoma), the usefulness of MR sagittal imaging for evaluating
      local extent (T factor) was examined by measuring the anteroposterior (AP)
      diameter of the tumor. The MR examination was performed using ECG gated scans
      with a 3 mm slice at 1.5 Tesla. T1-weighted sagittal images were obtained. In 10
      patients the appearance of the esophagus was normal, and in 44 patients a tumor
      was detected in the sagittal section. Thirty-seven lesions were histologically
      proved (Tis, 1; T1, 3; T2, 3; T3, 15; T4, 15). Lesions classified as <T2 were not
      visible, and the appearance of the esophagus was normal. The tumors detected in
      sagittal section were T3 (15 tumors) or T4 (15 tumors). The mean diameter of T4
      lesions (34.0 +/- 7.9 mm, range 24-57 mm) was larger than that of T3 lesions
      (25.0 +/- 4.4 mm, range 18-33 mm) (p < 0.05). Only two masses with an AP diameter
      > 30 mm were resected. They were located in the lower esophagus. It is concluded
      that lesions detected in MR sagittal images might be T3 or T4 tumors, and masses
      of >30 mm might extend to adjacent organs, although two tumors with an AP
      diameter < 25 mm also invaded the trachea.

PMID- 9000351
TI  - Dynamic MR imaging for extraserosal invasion of advanced gastric cancer.
AB  - Dynamic magnetic resonance (MR) images in 37 patients with gastric cancers were
      obtained by a two-dimensional fast multiplanar spoiled gradient technique. The
      degree of tumor invasion was classified into four grades regarding a low
      intensity band between the stomach and surrounding fat. Advanced gastric cancer
      was strongly enhanced, appearing as a thickened wall, by the contrast medium
      during the early to delayed phases of dynamic studies. The extent of invasion of
      the adjacent organs was diagnosed by the difference in enhancement between the
      tumor and the parenchyma. The sensitivity of extraserosal invasion was 93%.
      Dynamic MR diagnosis is useful for evaluating the extent of gastric carcinoma.

PMID- 9000350
TI  - TNM staging of gastrointestinal tumors by hydrosonography: results of a
      histopathologically controlled study in 60 patients.
AB  - BACKGROUND: The study is a prospective evaluation of preoperative TNM staging of
      gastrointestinal tumors by hydrosonography (HUS). METHODS: Sixty patients with
      suspected gastric or colorectal cancer underwent HUS for TNM staging. All
      patients were operated on and the tumors completely removed when possible. HUS
      findings were correlated with histopathologic staging. RESULTS: HUS correctly
      localized tumors in 75% of patients. T stage accuracy was low for gastric cancers
      (41%). N staging of gastric cancers was accurate in 68% of all cases and was
      highly specific (100%). Staging was more accurate for colorectal tumors (70%),
      especially with respect to infiltration of other structures (sensitivity 100%,
      specificity 95%). N staging, however, was not reliable, mostly owing to impaired
      examination conditions. CONCLUSION: HUS easily misses tumors of the gastric
      cardia and distal part of the rectum. T staging of colorectal tumors with HUS is
      highly accurate, reaching 92% if the tumor is localized. T1 cancers of the
      stomach tend to be overstaged, and serosal infiltration by gastric cancers is
      often misjudged. With the exception of cardial gastric and distal rectal cancers,
      HUS comes close to endosonography for staging gastrointestinal tumors. HUS does
      not require intraluminal access.

PMID- 9000352
TI  - Barium enema and colonoscopy: appropriateness of utilization in a Medicaid
      population.
AB  - BACKGROUND: To assess the appropriateness of utilization patterns for the barium
      enema and colonoscopy in a Medicaid population. METHODS: From 1987 to 1991, a
      Medicaid managed-care database in Philadelphia revealed claims for a total of
      2357 outpatient barium enemas and 896 outpatient colonoscopic examinations. The
      database was reviewed to determine the primary diagnostic (ICD-9-CM) codes
      assigned to patients who underwent these procedures. These codes were used as a
      proxy for indications. Each of the diagnostic codes for barium enema and
      colonoscopy was then classified either as appropriate, inappropriate, equivocal,
      or miscoded based on current guidelines in the medical literature. RESULTS: A
      total of 1962 claims (83%) for barium enema were classified as appropriate, 126
      (5%) as inappropriate, 84 (4%) as equivocal, and 185 (8%) as miscoded, whereas
      645 claims (72%) for colonoscopy were classified as appropriate, 176 (20%) as
      inappropriate, 65 (7%) as equivocal, and 10 (1%) as miscoded. Thus, significantly
      more colonoscopic examinations were rated as inappropriate (p < 0.001).
      CONCLUSION: Our study suggests that more stringent criteria need to be used by
      physicians in ordering diagnostic examinations of the colon, particularly
      colonoscopy. Further investigation of the appropriateness of these procedures and
      the development and dissemination of guidelines seems warranted.

PMID- 9000353
TI  - CT and MR findings of torsion of greater omentum: a case report.
AB  - We report a case of torsion of the greater omentum, which occurred in a 39-year
      old man with an adhesive inguinal hernia. Preoperative computed tomography and
      magnetic resonance (MR) imaging showed a characteristic whirling fatty mass
      occupying the middle and lower abdomen anteriorly. MR imaging also showed
      difference of intensities in the twisted omentum, suggesting the presence of the
      pathological conditions of edema or congestion.

PMID- 9000354
TI  - Intraperitoneal fat sign.
AB  - In a patient with an ovarian cystic teratoma and the peritoneal cavity filled
      with sebaceous material, an abdominal radiograph revealed a wide fat stripe
      between the parietal peritoneum and the lateral wall of the ascending colon. We
      called the existence of the wide fat stripe, which implied large amounts of
      intraperitoneal fatty material, the "intraperitoneal fat sign."

PMID- 9000355
TI  - Tuberculous chylous ascites: pathognomonic CT findings.
AB  - The computed tomographic (CT) appearance of chylous ascites is usually that of
      water with corresponding attenuation coefficients. This case report depicts the
      fat-fluid level sign on CT (shown by supine and decubitus scans), which is
      pathognomonic of chylous ascites.

PMID- 9000356
TI  - Demonstration of false-negative findings on CT hepatic angiography.
AB  - False-negative findings on CT angiography (CTA) in two patients with
      hepatocellular carcinoma (HCC) were demonstrated. CTA images of one patient with
      an aberrant left hepatic artery branching from the left gastric artery and
      another patient whose right hepatic artery was occluded owing to an unknown cause
      failed to demonstrate HCCs. This report suggests one of the diagnostic pitfalls
      of CTA for diagnosis of liver tumors.

PMID- 9000357
TI  - Nonpathological focal enhancements on spiral CT hepatic angiography.
AB  - BACKGROUND: To assess the frequency and characteristics of nonpathological focal
      enhancements seen on spiral computed tomographic (CT) hepatic angiography (CTA).
      METHODS: Spiral CTA and spiral CT arterial portography (CTAP) were performed in
      31 patients with suspected liver malignancy prior to potential liver resection.
      The CTA images were retrospectively reviewed for focal enhancements by two
      radiologists. After determining nonpathological focal enhancements on CTA images
      based on the other radiographic tests, surgical exploration including
      intraoperative sonography, follow-up imagings, the frequency, size, site, and
      shape of nonpathological focal enhancements with CTA were assessed. RESULTS:
      Thirty-six nonpathological focal enhancements with CTA from 4 to 23 (mean = 11.
      4) mm were seen in 14 (45.2%) of 31 patients. Thirteen (36.1%) of 36
      nonpathological focal enhancements with CTA were not depicted with CTAP.
      Nonpathological focal enhancements with CTA were frequent in Couinaud segments
      III (27.8%), V (22.2%), and VI (19.4%). Twenty-three (63.9%) of 36
      nonpathological focal enhancements were located in the edge of the liver. Shapes
      of 36 nonpathological focal enhancements with CTA included circular (n = 16),
      worm (n = 7), irregular (n = 6), dot (n = 6), and wedge (n = 1). CONCLUSION: In
      nearly half of patients, spiral CTA shows various shapes of small nonpathological
      focal enhancements more frequently in the liver edge.

PMID- 9000358
TI  - MR imaging of hepatocellular carcinomas: effect of Cu and Fe contents on signal
      intensity.
AB  - BACKGROUND: To elucidate the metallic factors contributing to the signal
      intensities of hepatocellular carcinoma (HCC) on T1-weighted magnetic resonance
      (MR) images and to determine whether or not changes in signal intensity
      contribute to the diagnosis of histological grading of HCC. METHODS: In 35
      patients immediately after surgery, the quantities of water, lipid, copper (Cu),
      iron (Fe), and manganese (Mn) were determined in HCCs and the surrounding hepatic
      parenchyma. The correlations among these findings, the histopathological
      findings, and the signal intensities of T1-weighted MR images were evaluated.
      RESULTS: Among the 35 HCCs, 12 (34%) were of high intensity, 14 (40%) were
      isointense, and 9 (26%) were of low intensity on T1-weighted images versus the
      surrounding hepatic parenchyma. The paramagnetic ions, which contributed to the
      signal intensity patterns, were assumed to be Cu in HCCs (30.5 +/- 52.9 microg/g
      ww), and Fe in the livers (106.2 +/- 86.8 microg/g ww) and HCCs (87.7 +/- 49.1
      microg/g ww). In 12 HCCs with high intensity, one was grade I, eight were grade
      II, and three were grade III according to Edmondson-Steiner's histopathological
      classification. CONCLUSIONS: Signal intensity and signal intensity patterns alone
      cannot be signs of low-grade malignancy because of the Fe in livers and in HCCs.

PMID- 9000359
TI  - Hepatic metastases from leiomyosarcoma: MR features with histopathologic
      correlation.
AB  - BACKGROUND: To determine the magnetic resonance (MR) imaging features of hepatic
      metastases from leiomyosarcoma and determine the pathologic basis for the MR
      appearance of these neoplasms. METHODS: MR examinations of eight patients with a
      total of 16 hepatic metastases from leiomyosarcoma were retrospectively reviewed.
      Hepatic metastases originated from a primary gastrointestinal (n = 6), uterine (n
      = 1), or retroperitoneal (n = 1) leiomyosarcoma. Correlation between MR features
      and pathologic findings was performed in 11 metastases from which histologic
      material was obtained. RESULTS: Among the 10 metastases seen on T1-weighted MR
      images, nine were homogeneous and one was heterogeneous. The latter contained
      areas of necrosis and hemorrhage on pathologic examination. Among the 16
      metastases seen on T2-weighted MR images, 12 were well delineated and completely
      homogeneous, with a marked hyperintense signal ("hemangiomalike" pattern). These
      neoplasms were composed of smooth fibrous tissue without macroscopically visible
      areas of necrosis on pathologic examination. The remaining four metastases were
      heterogeneous and contained varying degrees of necrosis and hemorrhage or
      gelatinous tissue. CONCLUSION: A hemangiomalike pattern is the most common
      feature on T2-weighted MR images. We found that homogeneous hyperintensity of
      hepatic metastases from leiomyosarcoma on T2-weighted MR image does not reflect
      cystic changes.

PMID- 9000360
TI  - Portal hypertension in children and young adults: sonographic and color Doppler
      findings.
AB  - Portal hypertension is a relatively uncommon pathologic condition in children and
      young adults in contrast with older adults. The aim of this study is to evaluate
      the utility of sonography and color Doppler sonography in the diagnosis of portal
      hypertension in children and young patients and to evaluate the sonographic
      pattern of each disease. We reviewed 25 such patients who were younger than 30
      years old and obtained the following sonographic findings: (1) liver cirrhosis:
      (a) multiple intrahepatic venovenous shunts in patients with primary Budd-Chiari
      syndrome and (b) intrahepatic vascular narrowing and nodular coarse parenchymal
      texture, with multiple very-high-echo spots along the portal vein in patients
      with Wilson disease; (2) congenital hepatic fibrosis: marked and developed
      collaterals, wide periportal echogenic band, and a heterogeneous parenchymal
      texture comprised of multiple high echoes but without portal thrombus; and (3)
      extrahepatic portal thrombosis: invisible portal lumen except as an echogenic
      band. Sonography and color Doppler sonography are very useful in diagnosing these
      portal hypertensive diseases. However, there are no specific sonographic
      findings, and the role of sonography is limited to follow-up observation of
      associated secondary hepatobiliary changes in patients with congenital biliary
      atresia.

PMID- 9000361
TI  - Large extrahepatic portosystemic shunt without portal hypertension.
AB  - Extrahepatic portosystemic shunt usually occurs secondary to severe portal
      hypertension, and it is rare to encounter it in patients without portal
      hypertension. We report herein a large extrahepatic portosystemic shunt between
      the left gastric vein and left renal vein without portal hypertension in which
      color Doppler sonography was useful not only for detection but evaluation of the
      effect of embolization.

PMID- 9000363
TI  - Carcinosarcoma of the extrahepatic bile ducts: cholangiographic and CT
      appearance.
AB  - A case of histologically proven carcinosarcoma arising in the extrahepatic
      biliary tree is presented. The tumor appeared on cholangiography and computed
      tomography as a large expansile intraluminal mass causing biliary obstruction.

PMID- 9000362
TI  - Gallbladder varices: demonstration of direct communication to intrahepatic portal
      veins by color doppler sonography and CT during arterial portography.
AB  - Gallbladder varices were correctly diagnosed by color Doppler sonography and
      computed tomography during arterial portography (CTAP) in two patients with
      portal vein thrombosis. One patient with multiple hepatocellular carcinomas
      showed extrahepatic and intrahepatic portal vein occlusion by a tumor thrombus.
      The other patient, with liver cirrhosis, had a portal vein thrombosis. Color
      Doppler sonography clearly showed the portal vein occlusion, cavernous
      transformation of collateral veins, and gallbladder varices that drained into the
      intrahepatic portal venous branches. The intrahepatic portal venous branch,
      connecting to the gallbladder varices, exhibited reverse flow from the periphery
      to the hilum of the liver. CTAP also demonstrated gallbladder varices
      communicating directly with the intrahepatic portal vein branches in both
      patients. Gallbladder varices developed as a venous collateral because of
      extrahepatic portal vein occlusion. Color Doppler sonography and CTAP are useful
      for detecting these varices and planning biliary surgery in patients with portal
      vein thrombosis.

PMID- 9000364
TI  - Radiologic features of papillary adenoma and papillomatosis of the biliary tract.
AB  - BACKGROUND: The purpose of this study was to describe the imaging findings of
      papillary adenoma of the bile ducts. METHODS: Imaging modalities including
      sonography, computed tomography, cholangiography, and endoscopic sonography
      obtained in five patients with papillary adenoma of the bile duct were
      retrospectively reviewed and correlated with pathologic findings. RESULTS: In
      four cases, imaging findings were a dilatation of the bile ducts due to a
      protruding mass within the lumen of the common bile duct. In one case, the
      biliary tract obstruction was not due to the mass but to mucus secretion that was
      detected at sonography, endoscopic sonography, and cholangiography. Multiple
      lesions were observed in two cases at pathology and not detected preoperatively.
      All the lesions contained foci of in situ carcinoma or mild dysplasia.
      CONCLUSION: Imaging is useful in detecting bile duct tumors. Hypersecretion of
      mucus is rare but highly characteristic of bile duct adenoma.

PMID- 9000365
TI  - Pelvic fistulas: appearances on MR images.
AB  - BACKGROUND: This multi-institutional study examines appearances of pelvic
      fistulas on magnetic resonance (MR) images. METHODS: MR images of 46 patients
      with documented fistulas from five teaching hospitals were retrospectively
      reviewed. All patients underwent T1-weighted (T1WI), T2-weighted (T2WI), and
      intravenous gadolinium chelate-enhanced T1-weighted (Gd-T1WI) images. Imaging
      sequences were separately and then collectively reviewed. The following
      determinations were made: fistula detection, fistula morphology and signal
      intensity, and the presence of associated abnormalities. Fistulas were classified
      into two categories: (1) fistulas that communicate with the bladder and (2)
      fistulas that do not communicate with the bladder. Fistulas within these two
      groups were subclassified further. The presence of fistulas was documented by
      surgery (five patients), endoscopy (six patients), fistulogram (20 patients), or
      physical exam (15 patients). RESULTS: Among the 46 patients, 53 fistulas were
      documented by means other than MR. Overall T1WI, T2W1 and Gd-T1WI images
      demonstrated 23, 31, and 39 of 53 fistulas, respectively. Gd-T1W1 detected
      significantly more fistulas than T1W1 (p < 0.05). Bladder fistulas were better
      shown on Gd-T1WI (8/15 fistulas) than on T1WI and T2WI (2/15 and 3/15) (p < 0.
      05). Nonbladder fistulas were demonstrated by T1WI, T2WI, and Gd-T1WI images in
      21, 28, and 31 of 38 fistulas, respectively. Among all fistulas, perianal
      fistulas (a subcategory of nonbladder fistula) had the highest detection by T1WI,
      T2WI, and Gd-T1WI in 19, 20 and 22 of 23 fistulas, respectively. On T1WI, 19 of
      23 detected fistulas were low in signal intensity. On T2WI, 28 of 39 detected
      fistulas were high in signal intensity. On Gd-T1WI images, 29 of 40 fistulas were
      low in signal intensity, with enhanced tract wall. CONCLUSION: Bladder fistulas
      were best shown on Gd-T1WI, which was significantly greater than on T1WI or T2WI.
      Nonbladder fistulas were comparably shown by all techniques, with all performing
      modestly well. Perianal fistulas were shown equally well by all MR sequences and
      were the fistulas demonstrated with the highest sensitivity on MR images.

PMID- 9000366
TI  - Renocolic fistulas: complementary roles of computed tomography and direct
      pyelography.
AB  - Three patients with renocolic fistulas are presented. Antegrade or retrograde
      pyelography showed the fistula in one patient but was unsuccessful in two others.
      CT demonstrated perinephric inflammation extending to the colon, complex air
      fluid collections within the kidney, or extension of renal contrast into the
      colon. CT and direct pyelography complement each other for the diagnosis of
      renocolic fistulas.

PMID- 9000367
TI  - Struma ovarii: MR appearances.
AB  - BACKGROUND: Analysis of unenhanced and contrast-enhanced magnetic resonance (MR)
      images of struma ovarii, a rare benign neoplasm of the ovary, is the aim of this
      study. METHODS: T2-weighted and Gd-DTPA-enhanced T1-weighted MR images of five
      histologically proven struma ovarii were evaluated retrospectively. RESULTS: In
      all patients, unenhanced and contrast-enhanced T1-weighted MR images showed
      complex cystic masses composed of multiple cysts and a solid component,
      indicating the presence of large and small thyroid follicles. In four patients,
      the cyst fluid was hypointense on T1-weighted images and hyperintense on T2
      weighted images. In one patient, the fluid was hyperintense on T1-weighted images
      and hypointense on T2-weighted images due to hemorrhage. CONCLUSION: A complex
      mass composed of multiple cysts and a solid component, indicating the presence of
      large and small thyroid follicles, appeared to be a characteristic MR finding of
      struma ovarii.

PMID- 9000368
TI  - MR imaging of cervical carcinoma: comparison among T2-weighted, dynamic, and
      postcontrast T1-weighted images with histopathological correlation.
AB  - BACKGROUND: To identify the reasons for misdiagnosis of the degree of stromal
      invasion by uterine cervical cancer with various magnetic resonance sequences.
      METHODS: T2-weighted, dynamic, and postcontrast T1-weighted images were obtained
      in the sagittal plane in 20 patients with uterine cervical cancer. After
      evaluating these sequences for the degree of stromal invasion, histologic
      specimens were directly correlated with these images. RESULTS: The degree of
      stromal invasion was correctly diagnosed in 15 of the 20 cases on T2-weighted
      images, in 12 on dynamic images, and in eight on postcontrast T1-weighted images.
      All misdiagnoses were due to overestimation. Histologically, peritumoral stroma
      showed inflammation or edema in two patients, whereas no histological abnormality
      was found in the other patients. A hyperintense rim, i.e. , a peritumoral
      enhanced ring-shaped structure, was observed on the enhanced images of five
      patients. The hyperintense rim corresponded to the periphery of the tumor in
      three patients and to the cervical stroma in two patients. CONCLUSION: T2
      weighted images permitted the most accurate evaluation of stromal invasion by
      uterine tumors. Overdiagnosis may be due to an abnormal intensity of the cervical
      stroma, which was observed more frequently on dynamic and postcontrast T1
      weighted images than on T2-weighted images.

PMID- 9000369
TI  - Sonographic detection of ingested foreign bodies in the inferior vena cava.
AB  - Ingested foreign bodies usually proceed uneventfully through the intestinal
      tract; complications rarely occur. The wide variety of clinical presentations
      they produce often make the diagnosis difficult. We report two cases of
      sonographic detection of foreign bodies in the inferior vena cava, namely one
      toothpick and one small (chicken?) bone, which probably caused a duodenocaval
      fistula. Both patients were initially investigated for recurrent septic episodes,
      weight loss, and deterioration of general condition.

PMID- 9000370
TI  - Retroperitoneal foregut cyst.
AB  - A foregut cyst is formed as a result of abnormal budding and pinching of the
      tracheobronchial tree when bronchial buds develop to form the primitive
      respiratory tree. Foregut cysts are clinically classified as bronchogenic,
      esophageal, enterogastric, or ciliated hepatic. We present a foregut cyst that
      occurred in the retroperitoneum and was difficult to distinguish from other
      retroperitoneal cystic mass lesions. Magnetic resonance imaging was useful in
      revealing the cyst's continuity to adjacent organs.

PMID- 9000371
TI  - Percutaneous decompression of an iliopsoas hematoma.
AB  - Spontaneous hematoma in the iliopsoas muscle is a serious complication of
      anticoagulant therapy. It causes severe pain and often results in loss of
      function of the femoral nerve. We present two cases in which percutaneous
      decompression of the hematoma was successfully performed to relieve intractable
      pain and to support functional restoration of the femoral nerve.

PMID- 9000374
TI  - Characterization of the Saccharomyces cerevisiae FCY1 gene encoding cytosine
      deaminase and its homologue FCA1 of Candida albicans.
AB  - By functional complementation of a fcy1 null mutant of Saccharomyces cerevisiae,
      we have cloned and characterized the FCY1 gene, encoding cytosine deaminase in
      Saccharomyces cerevisiae, and its homologue FCA1, encoding cytosine deaminase in
      Candida albicans. Disruption of FCY1 resulted in high resistance to 5
      fluorocytosine (10(-2) M) and in total loss of cytosine deaminase activity. By
      contrast the transformation by FCY1 or FCA1 of the haploid FCY1-disrupted host
      strain restored sensitivity to 5-fluorocytosine and allowed growth on cytosine,
      as a source of pyrimidine, or ammonium. FCA1 as opposed to FCY1 contains an
      intron. FCA1 and FCY1 encode respectively 150- and 158- residue proteins of 60%
      identity. Both Fcy1p and Fca1p share common motifs with cytidine and CMP
      deaminases, but homology with cytosine deaminase of E. coli could not be
      detected.

PMID- 9000375
TI  - Isolation of early meiotic recombination genes analogous to S. cerevisiae REC104
      from the yeasts S. paradoxus and S. pastorianus.
AB  - The REC104 gene of Saccharomyces cerevisiae is required to initiate recombination
      in meiosis. Mutations in REC104 eliminate meiotic recombination and lead to the
      production of inviable spores. To determine if analogous genes exist in other
      yeasts, clones that hybridized to a REC104 probe were isolated from the yeasts S.
      paradoxus and S. pastorianus. When transformed into a rec104 strain, the REC104
      analogs from these two yeasts restored spore viability and meiotic recombination
      to the same level as a REC104 gene cloned from S. cerevisiae. Compared to S.
      cerevisiae, the S. paradoxus gene codes for 79% identical amino acids and has 86%
      nucleic-acid identity in the promoter region and 84% in the coding region. The S.
      pastorianus gene codes for 63% identical amino acids and has 59% and 71% identity
      in the promoter and the coding regions, respectively.

PMID- 9000376
TI  - Analysis of a transketolase gene from Kluyveromyces lactis reveals that the yeast
      enzymes are more related to transketolases of prokaryotic origins than to those
      of higher eukaryotes.
AB  - The role of the pentose-phosphate pathway in carbohydrate metabolism of the yeast
      Kluyveromyces lactis, and the evolutionary relationships between the encoding
      genes, was investigated. For this purpose, we isolated the gene encoding
      transketolase (KlTKL1) and determined its nucleotide sequence. Surprisingly,
      comparisons of the deduced amino-acid sequence with those from other organisms
      revealed that the yeast enzymes are more related to those from prokaryotic
      sources than to those from higher eukaryotes. Functional analyses showed that
      KlTKL1 also complemented a Saccharomyces cerevisiae tkl1 tkl2 double mutant for
      growth in the absence of aromatic amino acids and restored transketolase activity
      in this mutant. A band detected in these transformants by Western-blot analysis
      corresponded to a band detected in K. lactis both in a wild-type strain and in a
      multicopy transformant with elevated transketolase activity.

PMID- 9000378
TI  - Improved biocontrol activity of Trichoderma harzianum by over-expression of the
      proteinase-encoding gene prb1.
AB  - Transformation systems developed for Trichoderma spp. were utilized to improve
      the biocontrol efficiency of the mycoparasitic fungus Trichoderma harzianum by
      increasing the copy number of the basic proteinase gene prb1. The transformants
      were stable and carried from two to ten copies of prb1. High levels of expression
      of prb1 during fungus-fungus interaction were detected when T. harzianum and
      Rhizoctonia solani were confronted in vitro. In liquid cultures the proteinase
      was induced by cell walls of R. solani. Under greenhouse conditions,
      incorporation of T. harzianum transformants into pathogen-infested soil
      significantly reduced the disease caused by R. solani in cotton plants.

PMID- 9000377
TI  - Arabinoxylan degradation by fungi: characterization of the arabinoxylan
      arabinofuranohydrolase encoding genes from Aspergillus niger and Aspergillus
      tubingensis.
AB  - The genes encoding the enzyme arabinoxylan arabinofuranohydrolase, which releases
      L-arabinose from arabinoxylan, have been cloned from the closely related fungi
      Aspergillus niger and Aspergillus tubingensis and were shown to be functional in
      A. niger. Integration of multiple copies in the genome resulted in over
      expression of the enzymes. The arabinofuranohydrolases encoded comprise 332 amino
      acids and have 94% amino acid identity. Their primary structure is not related to
      those of other alpha-L-arabinofuranosidases, except for a low similarity with
      XYLC, a bacterial alpha-L-arabinofuranosidase from Pseudomonas fluorescens which
      acts on oat spelt xylan. The axhA expression pattern in A. niger differed from
      that of abfB, since it was strongly induced by birchwood xylan and much less by L
      arabitol or L-arabinose. Furthermore, Northern analysis revealed that axhA
      expression was de repressed in creAd mutants and carbon catabolite repressed by D
      glucose.

PMID- 9000379
TI  - 3-Hydroxy-3-methylglutaryl-CoA reductase gene of Gibberella fujikuroi: isolation
      and characterization.
AB  - 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) is the first specific enzyme of
      the isoprenoid pathway, which leads to several classes of primary and secondary
      metabolites such as sterols, quinones, carotenoids and gibberellins. The
      structural gene of HMG-CoA reductase was isolated from the ascomycetous fungus
      Gibberella fujikuroi. Additionally, the most conserved region of this gene was
      also isolated from another plant pathogenic fungus, Sphaceloma manihoticola. Both
      ascomycetous fungi use the plant hormone gibberellin to induce an elongation of
      infected host plants, and in the case of S. manihoticola of plant tumors.
      Sequence analysis revealed a high degree of similarity between the deduced amino
      acid sequences in the C-terminal catalytic domains of all known HMG-CoA
      reductases, but the highest degree was found between the sequences of both
      analysed ascomycetes. In contrast to Saccharomyces cerevisiae, Ustilago maydis
      and plants, G. fujikuroi and S. manihoticola possess only a single copy of this
      gene, although the product of HMGR (mevalonate) is the precursor for essential
      sterol and quinone biosynthesis and secondary metabolites such as gibberellins.
      RNA-blot and hybridization experiments showed that gene expression is not
      influenced by either glucose or ammonium excess.

PMID- 9000380
TI  - Partial sequence of the mitochondrial genome of the crustacean Daphnia pulex.
AB  - A 4062-nucleotide (nt) fragment of the mitochondrial genome of the crustacean
      Daphnia pulex was sequenced and found to contain the complete genes for eight
      tRNAs and five proteins (ATP6, ATP8, COII, COIII, ND3) and the partial sequence
      of COI. In combination with data described previously, approximately 50% of the
      D. pulex mitochondrial genome has been sequenced. The gene order in this half of
      the genome is identical to that of Drosophila yakuba which differs from that of
      the other completely sequenced crustacean mitochondrial genome, Artemia
      franciscana. Comparison of seven mitochondrial proteins among D. pulex, A.
      franciscana, D. yakuba, Anopheles gambiae, Locusta migratoria and Apis mellifera
      showed that, with one exception, the D. pulex proteins are most similar in length
      and sequence to the proteins of the dipteran insects. Conversely, patterns of
      nucleotide bias at third codon positions in fourfold degenerate codon families
      are very similar in the two crustaceans but differed substantially from the
      insects.

PMID- 9000381
TI  - A mitochondrial sub-stoichiometric orf87-nad3-nad1 exonA co-transcription unit
      present in solanaceae was amplified in the genus Nicotiana.
AB  - Unlike other plant species, two copies of nad3 are present in Nicotiana
      sylvestris mitochondria. Both are localized downstream from an open reading frame
      (orf87 ), and are associated with either rps12 or the first exon of the nad1
      gene. The orf87-nad3-nad1/A cluster is present in normal stoichiometry in
      Nicotiana tomentosiformis and is sub-stoichiometric in other Solanaceae,
      revealing recent amplification in the genus Nicotiana. It is suggested from
      sequence analysis that this cluster originated in an homologous recombination
      event that involved the nad3-rps12 intergenic region and the upstream region of
      an ancestral nad1 gene. Transcription patterns and RT-PCR showed that orf87-nad3
      rps12 and orf87-nad3-nad1/A clusters are both co-transcription units.

PMID- 9000382
TI  - Genes encoding subunit 6 of NADH dehydrogenase and subunit 6 of ATP synthase are
      co-transcribed in maize mitochondria.
AB  - The mitochondrial nad6 gene of maize was identified and mapped 1 kb downstream
      from the atp6 gene. It encodes a 220 amino-acid polypeptide. Using Northern
      hybridization experiments and RT-PCR analysis, we showed that both nad6 and atp6
      are co-transcribed in maize mitochondria. RNA editing of the mitochondrial nad6
      transcript was studied by cDNA sequencing. Twelve edited sites were identified at
      the same positions as those already identified in the wheat mitochondria nad6
      transcript. Alignments of nucleotide and amino-acid sequences of the
      mitochondrial nad6 genes of maize, wheat, and Brassica campestris, show that the
      wheat gene encodes a shorter polypeptide (229 amino acids) than was previously
      thought.

PMID- 9000383
TI  - An open reading frame for a protein involved in cytochrome c biogenesis is split
      into two parts in Brassica mitochondria.
AB  - A plant mitochondrial gene with sequence similarity to ccl1, a bacterial gene
      involved in cytochrome c biogenesis, occurs as a single open reading frame in
      wheat, Oenothera, carrot and Marchantia mtDNAs. In Brassica napus "Polima" or
      Brassica campestris mtDNA, however, this open reading frame is split into two
      segments that are located 60 kb apart on the master-circle form of the genome.
      Although transcripts of the split ORF are edited in a manner similar to that of a
      functional gene, transcripts that span both portions of the ORF are not evident
      in gel-blot hybridization experiments. Low-abundance transcripts that span both
      portions of the split ORF can be detected by RT-PCR, but these contain an
      additional 54-bp sequence, inserted between the two segments, that is unrelated
      to the corresponding sequences of other plants. Since this additional sequence
      introduces an in-frame stop codon, no transcripts have been found that could be
      translated to yield a protein product of a size similar to that present in other
      plant species. An antiserum directed against the product of the corresponding
      wheat gene detects polypeptides of similar size in wheat and Brassica
      mitochondria. This antiserum, however, immunoprecipitates a labelled polypeptide
      from the products of wheat, but not Brassica, in organello protein synthesis. Gel
      blot analysis of total Brassica DNA indicates that sequences capable of
      hybridizing with the ORF are present in the nuclear genome. We suggest that the
      functional form of the Brassica gene may reside in the nucleus.

PMID- 9000384
TI  - Group-I introns in the cytochrome c oxidase genes of Dictyostelium discoideum:
      two related ORFs in one loop of a group-I intron, a cox1/2 hybrid gene and an
      unusually large cox3 gene.
AB  - The DNA sequences of cytochrome oxidase (subunits 1, 2 and 3) genes of the
      cellular slime mold Dictyostelium discoideum mitochondria were determined. The
      genes for subunits 1 and 2 have a single continuous ORF (COX1/2) which contains
      four group-I introns. The insertion sites of the two group-I introns (DdOX1/2.2
      and DdOX1/2.3) coincide with those of fungal and algal group-I introns, as well
      as a liverwort group-I intron, in the cytochrome oxidase subunit 1.
      Interestingly, intron DdOX1/2.2 has two free-standing ORFs in a loop (L8) which
      have similar amino-acid sequences and are homologous to ai4 DNA endonuclease (I
      Sce II) and bi4 RNA maturase found in group-I introns of Saccharomyces cerevisiae
      mitochondrial DNA. Two group-I introns (DdOX1/2.3 and DdOX1/2.4) also have a free
      standing ORF in loop 1 and loop 2, respectively. These results show that these
      group-I introns and the intronic ORFs have evolved from the same ancestral
      origin, but that these ORFs have been propagated independently.

PMID- 9000385
TI  - Two new group-II twintrons in the Euglena gracilis chloroplast are absent in
      basally branching Euglena species.
AB  - Studies of the phylogeny and chloroplast intron content of selected Euglena
      species have led to insights in our understanding of the timing of intron
      acquisition. In the current study, two new twintrons, found in E. gracilis, have
      been characterized by the analysis of partially spliced pre-mRNAs. Intron 1 of
      atpE is a 463-nt group-II intron interrupted by a second group-II intron 320 nt
      long. Intron 1 of psbD is also a group-II twintron with external and internal
      introns of 635 nt and 463 nt, respectively. The two introns composing the psbD
      twintron, as well as six additional group-II introns found in the E. gracilispsbD
      gene, are not present in several basally branching Euglena species, including E.
      myxocylindracea, E. stellata and E. viridis. The distribution of psbD introns in
      Euglena is consistent with a late evolutionary acquisition of group-II introns in
      this lineage.

PMID- 9000386
TI  - Infectious ileocecitis caused by Yersinia, Campylobacter, and Salmonella:
      clinical, radiological and US findings.
AB  - Yersinia, Campylobacter, and Salmonella are pathological microorganisms which
      incidentally may specifically infect the ileocecal area (infectious ileocecitis).
      In such cases pain in the right lower quadrant is the predominant symptom, and
      diarrhea is absent or only mild. This symptomatology can lead to an unnecessary
      laparotomy for suspected appendicitis. At surgery a normal appendix is removed,
      while there is edematous thickening of ileum and cecum, and enlarged mesenteric
      lymph nodes. These ileocecal abnormalities give rise to a fairly characteristic
      US image, enabling the radiologist to rapidly differentiate infectious
      ileocecitis from appendicitis, thus preventing an unnecessary laparotomy.
      Infectious ileocecitis caused by Yersinia, Campylobacter, and Salmonella is a
      common mimicker of appendicitis, and its incidence at this moment is grossly
      underestimated. Ultrasound is presently the only means to prevent an unnecessary
      operation for this condition which is principally self-limiting and innocuous.

PMID- 9000387
TI  - Effects of lipiodol retention on MRI signal intensity from hepatocellular
      carcinoma and surrounding liver treated by chemoembolization.
AB  - Opinion is divided regarding the influence of iodized oil on MRI signal intensity
      of hepatic tumours treated with transcatheter arterial chemoembolization (TACE),
      in which lipiodol deposits. The aim of our study was to ascertain whether or not
      lipiodol directly influences the MRI signal intensity of hepatocellular carcinoma
      (HCC) treated by TACE and that of the surrounding liver. Thirteen patients with
      HCC were studied retrospectively. CT and MRI scans were performed both before and
      3 months after TACE. The CT scan was performed to check whether embolized nodules
      contained lipiodol and how lipiodol was distributed within them. In addition,
      eight patients were examined prospectively within 7 days after TACE. In these
      patients a CT scan was performed to see how lipiodol was distributed in the
      neoplastic nodules and in normal hepatic parenchyma. In the first group of
      patients the contrast-to-noise (C/N) ratio on T1-weighted (T1W) images and the T2
      relaxation time on T2-weighted (T2W) images were calculated for both neoplasm and
      surrounding liver. In the second group of patients we also measured the signal
      intensity of non-neoplastic liver that was either permeated or not permeated by
      lipiodol. The data were analysed with Wilcoxon's test. On T1W images we observed
      that the retention of lipiodol increased the C/N ratio in all the tumours studied
      within 1 week after TACE. In the patients studied 3 months after TACE the C/N
      ratio was not significantly increased. On T2W images lipiodol retention did not
      change tumour signal intensity. The iodized oil did not change the signal
      intensity of the liver surrounding the tumour, in comparison with the liver not
      permeated by lipiodol, on either T1W or T2W images. The results indicate that
      lipiodol does not modify the signal intensity in non-neoplastic hepatic
      parenchyma in which it is deposited; after 3 months it does not significantly
      affect the signal of the tumours that accumulated it. Lipiodol produces a high
      signal on T1W images over the first few days following TACE in those tumours in
      which it is deposited.

PMID- 9000388
TI  - Contrast-enhanced magnetic resonance imaging for the detection of acute
      haemorrhagic necrotizing pancreatitis.
AB  - Eleven piglets with haemorrhagic necrotizing pancreatitis and nine piglets with
      oedematous pancreatitis were imaged using a multi-breath-hold TurboFLASH (TR 6.5
      ms, TE 3 ms, TI 300 ms, flip angle 8 degrees , three slices) pre-excited T1
      weighted sequence with an IV bolus injection of gadopentetate dimeglumine (Gd
      DTPA, 0. 3 mmol/kg) as a contrast agent to show dynamic contrast enhancement of
      the pancreas by MRI. All piglets were imaged according to the same protocol
      before inducing the disease. Following the IV Gd-DTPA bolus, time-enhancement
      curve of the pancreas during haemorrhagic necrotizing pancreatitis was
      significantly lower than during oedematous pancreatitis. The enhancement curves
      for the healthy piglets and piglets with oedematous pancreatitis did not differ
      significantly. Each piglet served as its own control. Because the results of this
      initial study are similar to those obtained with contrast-enhanced CT, we
      conclude that our results may encourage further clinical trials, and contrast
      enhanced dynamic MRI may be an alternative to the established method of CT for
      diagnosing acute haemorrhagic necrotizing pancreatitis.

PMID- 9000389
TI  - Intravascular ultrasound for evaluation of portal venous involvement in
      pancreatic cancer.
AB  - The aim of this study was to evaluate the accuracy of intravascular ultrasound
      (IVUS) in diagnosing tumour involvement of the portal vein in patients with
      exocrine cancer of the head of the pancreas. Seven consecutive patients with a
      preoperative diagnosis of carcinoma, preoperatively deemed to be resectable, were
      examined with IVUS of the portal vein during surgery. The IVUS catheters were 6.2
      F (2.0 mm) in diameter with a 20-MHz transducer and were introduced into the
      portal vasculature through the mesenteric superior vein. All patients had tumour
      extending to the portal vein as demonstrated at histopathological examinations in
      six cases and at surgical dissection in one case. The IVUS technique correctly
      identified all these patients, whereas five patients were incorrectly deemed at
      surgery not to have tumour involvement of the portal vein. These results indicate
      that IVUS is a very sensitive method for the evaluation of tumour involvement of
      the portal vein.

PMID- 9000390
TI  - Comparison between transrectal ultrasonography and computed tomography with
      rectal inflation of gas in preoperative staging of lower rectal cancer.
AB  - Computed tomography with rectal air insufflation was compared with transrectal
      ultrasonography (TRUS) in 63 patients. The CT protocol involved pre- and
      postcontrast scans with 5 mm slice thickness following air insufflation in IV
      antiperistaltic agent. Of the patients, 79 % were scanned in the prone position.
      Results of the preoperative examinations were compared with the histological
      findings. The CT examination had an accuracy rate of 74 %, predicting perirectal
      spread with a sensitivity of 83 % and a specificity of 62 %, whereas the
      corresponding figures for TRUS were 83, 91 and 67 %. The accuracy, sensitivity
      and specificity of CT and TRUS for nodal involvement were 57, 56, 57, 66, 68 and
      64 %-respectively. These findings confirm that TRUS is more accurate than CT in
      local tumour (T) staging and in detecting nodal (N) spread. However, the
      appropriate CT technique shows spread of tumour outside the rectal wall and
      locoregional lymph nodes with reasonable accuracy. Lymphatic spread correlated
      with nodal size. TRUS and CT correctly staged only 57 and 43 %, respectively, of
      cases with nodal metastases with maximum diameter of 5 mm. TRUS sometimes
      overstaged perirectal growth of tumour in 7 patients, due to inflammation (5
      patients) or incorrect positioning of the balloon in relation to the tumour
      surface (2 patients).

PMID- 9000391
TI  - Magnetic resonance imaging evaluation of incision healing after cesarean
      sections.
AB  - The purpose of this study was to examine the healing period of incision scar in
      myometrial wall and the normal pelvis after cesarean sections by means of MRI. In
      this study 17 voluntary women were examined after their first delivery with
      cesarean section in the early postpartum period (first 5 days), and following
      this, three more times in 3-month intervals. The MRI examinations were performed
      on a 1.0-T system (Magnetom, Siemens, Erlangen, Germany), and sagittal T1
      weighted (550/17 TR/TE) and T2-weighted (2000/80 TR/TE) spin-echo (SE) images of
      the pelvis were obtained. During follow-up examinations incision scar tissues
      lost their signals within the first 3 months on both SE sequences, and little
      alteration was observed in the subsequent tests. Zonal anatomy of the uterus
      reappeared completely 6 months after cesarean sections. The time for the
      involution of the uterus was independent of the zonal anatomy recovery, and the
      maximum involution was inspected within the first 3 months. In conclusion, the
      maturation time of myometrial scar tissue in uncomplicated cesarean sections,
      which can be evaluated by the signal alterations in MRI, is approximately 3
      months, whereas the complete involution and the recovery of the zonal anatomy
      need at least 6 months.

PMID- 9000392
TI  - Benign hyperplasia in ectopic prostatic tissue: a rare cause of pelvic mass.
AB  - Four cases of a pelvic mass due to the development of benign hyperplasia within
      ectopic prostatic tissue are reported. They presented a hypoechoic homogeneous or
      heterogeneous pattern on transrectal ultrasonography and a high signal intensity
      on T2-weighted spin-echo sequences on MR. On CT the density was similar to that
      of prostatic tissue. No recent imaging findings of this rare entity have been
      described in the literature. Possible aetiologies are discussed. Even if it is a
      rare event, the correct diagnosis can be reached. It is important for
      radiologists to consider the presence of this lesion because of its benign
      nature.

PMID- 9000393
TI  - Multiple adrenal masses: MRI tissue differentiation of pheochromocytoma and
      adenoma at 1.5 T.
AB  - We present the case of 38-year-old hypertensive patient with bilateral adrenal
      masses and with clinical and biochemical suspicion of pheochromocytoma. Magnetic
      resonance imaging at 1.5 T established correct diagnosis of coexisting adrenal
      pheochromocytoma and adenoma (nonhyperfunctioning). The case supports the
      usefulness of MRI for definitive evaluation of bilateral adrenal masses in
      patients with suspicion of pheochromocytoma.

PMID- 9000394
TI  - Radiologists and visual acuity.
AB  - Visual acuity (VA) and potential risks to the radiologist's eyesight have been
      relatively neglected subjects in the radiological literature. This study
      comprises two parts, the first consisting of a questionnaire on this subject sent
      to a random sample of 480 practising radiologists in the United Kingdom, and the
      second, a spot check of the VA of radiologists in our department. Of
      questionnaires, 73 %were returned. Of respondents, 76 % felt that ionising
      radiation could affect their vision, but only 13 % used lead glasses on a regular
      basis. A total of 71 % felt that regular monitoring of eyesight should be
      required. Of 25 tested radiologists, 5 had suboptimal VA and could benefit from
      further correction. The pertinent literature is reviewed, and a case for periodic
      eyesight testing is presented, including VA and grey-scale discrimination.

PMID- 9000395
TI  - Takayasu's arteritis: evaluation with three-dimensional time-of-flight MR
      angiography.
AB  - Three-dimensional time-of-flight MR angiography was performed in 16 patients with
      Takayasu's arteritis. Two regions were evaluated, the arch of aorta and its
      intrathoracic major branches, and the abdominal aorta with proximal portions of
      its major visceral and renal branches. Individual arteries and aortic segments,
      i. e. aortic arch and abdominal aorta, were evaluated for abnormalities such as
      stenosis, occlusion, dilatation and aneurysm formation. The results were compared
      with contrast angiography. Follow-up MR angiography was performed in three
      patients after 9-12 months. MR angiography demonstrated steno-occlusive lesions
      in all the patients and aneurysms in 2. In comparison with contrast angiography,
      good correlation was found in 129 of the 145 arteries and aortic segments. For
      the 12 false-positive results, incorrect slab placement and overestimation of
      stenosis were implicated. Interestingly, there were three false-negative results
      and one occlusion was underestimated as stenosis. A new lesion developed in 1
      patient and one stenosis progressed in another patient upon follow-up. Three
      dimensional time-of-flight MR angiography is a simple and fairly accurate method
      for documenting the lesions in Takayasu's arteritis and for its follow-up.

PMID- 9000396
TI  - Intramural posttraumatic hematoma of the ascending aorta in a patient with a
      double aortic arch.
AB  - We report a case of posttraumatic intramural hematoma (IMH) of the ascending
      aorta in a patient with a double aortic arch and coronary artery disease. This
      unusual and asymptomatic finding came to our observation because the patient
      presented an acute myocardial infarction and underwent coronary angiography. The
      diagnosis was performed by magnetic resonance imaging (MRI) which defined well
      the anatomy of aorta and showed the characteristics of the hematoma. The data
      were useful in planning the surgical repair.

PMID- 9000397
TI  - Evolution of salmonella aortitis towards the formation of abdominal aneurysm.
AB  - We present a case of salmonella aortitis with necrosis of the arterial wall and
      its evolution to the formation of an abdominal aneurysm over a 6-day period.
      Computed tomography was performed before and after the development of a mycotic
      aneurysm. Presurgical aortography was also performed. The findings obtained give
      a dynamic concept to this pathology and show its rapid evolution in a short
      period of time.

PMID- 9000398
TI  - Accuracy of the diagnosis of pleural effusion on supine chest X-ray.
AB  - Diagnosis of pleural effusion (PE) on supine chest X-ray (SCXR) is considered
      difficult. This study aimed at evaluating the accuracy of the diagnosis of PE on
      SCXR and was performed in two phases. At phase 1, a formula for the sonographic
      estimation of the volume of PE was established by correlating 24 measurements (in
      7 patients in whom complete drainage was achieved) with the drained volumes. At
      phase two, 112 consecutive SCXRs were supplemented by sonography of the chest.
      The films were evaluated for the presence of PE and for the presence of different
      radiologic signs of PE. Sonography showed PE in 41 right and 30 left
      hemithoraces. The overall accuracy of the diagnosis of PE on SCXR was 82 %. Only
      one of the undiagnosed PEs had a volume of > 300 ml. The most accurate signs were
      increased density of the hemithorax, blunted costophrenic angle, and loss of the
      hemidiaphragm silhouette.

PMID- 9000399
TI  - Diagnostic value of 3D CT surface reconstruction in spinal fractures.
AB  - Our purpose was to evaluate the diagnostic value of three-dimensional (3 D) CT
      surface reconstruction in spinal fractures in comparison with axial and
      reformatted images. A total of 50 patients with different CT-proven spinal
      fractures were analysed retrospectively. Based on axial scans and reformatted
      images, the spinal fractures were classified according to several classifications
      as Magerl for the thoraco-lumbar and lower cervical spine by one radiologist.
      Another radiologist performed 3 D CT surface reconstructions with the aim of
      characterizing the different types of spinal fractures. A third radiologist
      classified the 3 D CT surface reconstruction according to the Magerl
      classification. The results of the blinded reading process were compared. It was
      checked to see in which type and subgroup 3 D surface reconstructions were
      helpful. Readers one and two obtained the same results in the classification. The
      3 D surface reconstruction did not yield any additional diagnostic information
      concerning type A and B injuries. Indeed, the full extent of the fracture could
      be easier recognized with axial and reformatted images in all cases. In 10 cases
      of C injuries, the dislocation of parts of vertebrae could be better recognized
      with the help of 3 D reconstructions. A 3 D CT surface reconstruction is only
      useful in rotational and shear vertebral injuries (Magerl type C injury).

PMID- 9000400
TI  - Pitfalls in sonography of the Gamekeeper's thumb.
AB  - The gamekeeper's or skier's thumb is a very common injury. Nondisplaced tears of
      the ulnar collateral ligament of the thumb (UCL) may be treated conservatively.
      For that reason an accurate diagnosis is mandatory for choosing the correct
      therapy. Ultrasound is able to depict the position of the torn UCL correctly in
      approximately 90 % of cases. Sonographic pitfalls can be caused by a dislocation
      of the palmar joint capsule to the ulnar joint space, by a scalloping of the
      adductor aponeurosis due to the displaced UCL, and by scar tissue or technical
      mistakes. It is important to know about those pitfalls because conservative
      treatment of displaced UCL tears leads to instability. Therefore, the use of MRI
      is recommended whenever a nondisplaced UCL tear is suspected by US and a
      conservative therapy is suggested. Splitting the diagnostic pathway between US
      and MRI and preferring conservative therapy in nondisplaced UCL tears should help
      to save money in this field.

PMID- 9000401
TI  - Diagnostic imaging of tibial periosteal ganglion.
AB  - A case of a soft tissue tumor situated in the anterior surface of the proximal
      end of the tibia in an adult patient is demonstrated by conventional radiographs,
      CT, and MRI. The lesion was well defined with respect to the adjacent soft
      tissue. The CT exam showed a soft tissue mass with external cortical erosion and
      thick spicules by periosteal reaction. On T1-weighted images the mass was
      homogeneous and of low signal intensity, whereas on T2-weighted images it showed
      a high signal intensity, with some septa in the mass. The differential
      considerations include a periosteal chondroma, a lipoma, a subperiosteal
      hematoma, an inflammatory process, a giant cell tumor of tendon sheath, and a
      parosteal osteosarcoma. The CT and MR features of these entities are reviewed as
      an aid in differential diagnosis of the periosteal ganglion.

PMID- 9000402
TI  - Hyperphosphatasemia: CT assessment.
AB  - Hyperphosphatasemia is a rare disorder of uncertain cause. A 39-year-old male
      exhibiting striking skeletal deformities consisting of enlargement of the skull,
      enlargement and bowing of the long bones, neurosensorial symptoms and elevated
      alkaline phosphatase is the subject of this report. In the past, the radiological
      workup has been limited to plain films. We advocate CT in the assessment of
      neurological signs and symptoms which may complicate this disease.

PMID- 9000403
TI  - Image quality and dose in computed tomography.
AB  - Radiation exposure to the patient during CT is relatively high, and it is
      therefore important to optimize the dose so that it is as low as possible but
      still consistent with required diagnostic image quality. There is no established
      method for measuring diagnostic image quality; therefore, a set of image quality
      criteria which must be fulfilled for optimal image quality was defined for the
      retroperitoneal space and the mediastinum. The use of these criteria for
      assessment of image quality was tested based on 113 retroperitoneal and 68
      mediastinal examinations performed in seven different CT units. All the criteria,
      except one, were found to be usable for measuring diagnostic image quality. The
      fulfillment of criteria was related to the radiation dose given in the different
      departments. By examination of the retroperitoneal space the effective dose
      varied between 5.1 and 20.0 mSv (milli Sievert), and there was a slight
      correlation between dose and high percent of "yes" score for the image quality
      criteria. For examination of the mediastinum the dose range was 4.4-26.5 mSv, and
      there was no significant increment of image quality at high doses. The great
      variation of dose at different CT units was due partly to differences regarding
      the examination procedure, especially the number of slices and the mAs (milli
      ampere second), but inherent dose variation between different scanners also
      played a part.

PMID- 9000404
TI  - Registered image subtraction for CT-, MR- and coronary angiography.
AB  - Conventional post-processing of digital subtraction angiography (DSA) by 3D
      spiral CT, 3D MRI and 2D DSA is often hampered by extended artefacts due to
      patient movements during examination. In this paper an image registration
      procedure prior to the digital subtraction is introduced allowing an enhanced
      visualization of the contrast agent. The object displacement is detected by
      analysis of image deformations in small local regions. The motion pattern is used
      to compute a new synthetic mask of maximum congruence with the contrast medium
      image. This new mask image is then used in the subsequent subtraction. The
      algorithm works fully automatically and does not need any interactive placement
      of landmarks. Results obtained from subtraction of uncorrected and corrected
      sequences were compared with each other. The registration procedure provided good
      results in the suppression of subtraction artefacts and in the enhancement of
      vascular structures. Results are presented from subtraction of 2D and 3D data
      from CTA, MR mammography and coronary angiography.

PMID- 9000406
TI  - Nasopharyngeal teratoma: CT and MR findings.
AB  - Teratomas of the nasopharynx occur usually in neonates. We present a case of
      teratoma which was discovered in an adult, and which relapsed after 34 years. The
      conventional radiograms, CT, MR, and histologic appearances are described.

PMID- 9000405
TI  - Usefulness of echo-color Doppler in differentiating parathyroid lesions from
      other cervical masses.
AB  - The aim of our study was to clarify possible differential color Doppler US
      features between parathyroid lesions and other cervical masses. A total of 56
      parathyroid lesions in 54 patients with primary hyperparathyroidism were
      preoperatively examined with color Doppler sonography. Color Doppler flow
      patterns were compared with those of 72 thyroid nodules and 20 cervical lymph
      nodes. In 38 parathyroid lesions a correlation between color Doppler patterns and
      size, location, and pathological findings was performed. Color Doppler sonography
      showed five vascular distribution patterns: pattern I, absence of flow; pattern
      II, focal peripheral flow ("vascular pole") with arterial Doppler spectrum;
      pattern III, peripheral flow; pattern IV, internal flow ("parenchymal pattern");
      pattern V, peripheral and intranodular flow. Pattern I was not specific for any
      cervical lesion considered. Conversely, pattern IV was observed solely in
      parathyroid lesions, and pattern II was observed in only one nonparathyroid
      lesion (thyroid nodule). Mixed pattern (pattern V) was observed solely in thyroid
      nodules. In addition, pattern III was a characteristic finding of thyroid nodules
      and was observed in only one parathyroid lesion. Color Doppler patterns of the
      parathyroid masses did not correlate with the size of the lesion or pathological
      findings, but only with the location of the gland. Our study showed that color
      Doppler assessment of parathyroid lesions is a useful integration of gray-scale
      US and may be helpful in distinguishing parathyroid lesions from other cervical
      masses.

PMID- 9000407
TI  - Cervical lymph node metastases of medullary thyroid carcinoma: CT findings.
AB  - Medullary thyroid carcinoma (MTC) is a rare malignancy which spreads frequently
      to cervical lymph nodes. We report the CT findings of MTC metastatic cervical
      adenopathies in two patients with previously resected MTC. The CT scans showed
      calcifications (one patient) and massive homogeneous postcontrast nodal
      enhancement. Medullary thyroid carcinoma should be included in the differential
      diagnosis of entities showing calcifications and intense homogeneous adenopathic
      enhancement on CT studies.

PMID- 9000408
TI  - First branchial complex anomalies: report of 3 cases.
AB  - Three cases of first branchial cleft anomalies are presented. The embryology and
      pathology of first branchial complex anomalies, their imaging characteristics and
      differential diagnosis are discussed.

PMID- 9000409
TI  - MRI versus CT in the diagnosis of Nelson's syndrome.
AB  - The purpose of the study was to evaluate the utility of MRI and CT in the
      diagnosis of Nelson's syndrome, i. e. pituitary tumours in patients bilaterally
      adrenalectomized for Cushing's disease. Thirteen patients, followed up for 5-29
      years after adrenalectomy, were studied. In 6 of them CT and MRI revealed no
      changes in the pituitary gland. In the remaining 7 patients only three CT scans
      were suggestive of a pituitary adenoma. MRI studies with administration of
      gadodiamide confirmed the CT diagnosis of Nelson's tumour in 3 patients and
      disclosed microadenomas in a further 4 patients. Neurosurgical treatment in 4
      patients confirmed the MRI findings. Additionally CT and MRI examinations were
      performed in 5 patients suspected of a recurrent Nelson's tumour 3-11 years after
      neurosurgery. MRI visualized recurrent adenomas in 3 patients that were not well
      seen by CT scans. In our experience MRI was more effective than CT in the
      diagnosis of Nelson's syndrome.

PMID- 9000410
TI  - Blood-ocular barrier damage: use of contrast-enhanced MRI.
AB  - The blood-ocular barrier (BOB) shares similar neuroepithelial origin,
      microanatomy and functions with the blood-brain barrier. There are many natural
      (e. g. diabetes, hypertension) or iatrogenic (chemotherapy, retinal
      photocoagulation) conditions which can cause a BOB breakdown, resulting in visual
      acuity impairment or loss. The authors examined 42 patients affected by BOB
      damage in different pathological conditions. All patients previously underwent a
      conventional fluoroangiographic (FA) study. Nine patients with normal FA exam
      were evaluated also. Despite normal MRI findings immediately after Gd-DTPA
      injection, contrast leakage into the vitreous body or into the aqueous fluid was
      demonstrated in delayed scans (40-50 min after contrast administration), proving
      the existence of a BOB damage (sensitively 94 %). Although FA exam remains the
      choice modality in BOB breakdown demonstration, we propose MRI as a useful
      diagnostic tool when optic media opacity (cataract, haemovitreous, intraocular
      silicon oil) occurs, preventing direct retinal fundus imaging and/or an early
      screening tool.

PMID- 9000411
TI  - Syndrome of Alagille: radiological and sonographic findings. A review of 37
      cases.
AB  - The objective of this study was to evaluate the association of intrahepatic
      cholestasis, pulmonary stenosis, and hyperlipemia with osseous and renal
      abnormalities in Alagille's syndrome. A total of 37 patients (25 males and 12
      females) with ages ranging between 8 months and 27 years were included. Clinical
      records as well as radiological and ultrasonographic studies were reviewed.
      Chronic cholestasis was observed in all patients. Thirteen had favorable clinical
      outcome and normal hepatic sonograms. Clinical and sonographic evidence of portal
      hypertension was found in 13 patients and of cirrhosis in 8 patients. The
      remaining 3 patients required hepatic transplantation due to severe cholestasis.
      Hyperlipemia correlated with hepatic malfunction. Pulmonary stenosis and renal
      hypoplasia were the most frequently associated abnormalities. All patients showed
      a peculiar facies. Abnormal "butterfly" vertebrae were present in 18 patients and
      ulnar or phalangeal shortening in 11 patients. Ultrasonography allowed
      hepatobiliary disease assessment and helped to establish indications for hepatic
      transplantation. Renal and osseous abnormalities were not specific but in the
      appropriate clinical setting reinforced the diagnosis.

PMID- 9000412
TI  - Radiation-induced esophageal strictures in children with cancer.
AB  - The purpose of this study was to determine the long-term esophageal side effects
      of irradiation and (doxorubicin) chemotherapy given to children with cancer.
      Barium esophagograms and medical records of 18 patients with esophagitis who
      received between 1200 and 5580 cGy to the chest and chemotherapy were reviewed.
      The age range was 3-14 years. Esophageal strictures occurring 1-10 years after
      therapy were found in 5 patients with lymphoma; 3 of the five received doses of
      4000 cGy or greater. Three children with esophagitis who received doses of 4000
      cGy did not have stricture formation. However, their follow-up time was only 1-3
      years. Of the 5 patients with esophageal stricture, 4 were treated with multiple
      dilatations, and a fifth required colonic interposition. Combined mediastinal
      irradiation and chemotherapy can result in esophageal stricture 1-10 years after
      therapy.

PMID- 9000413
TI  - Klippel-Trenaunay syndrome: a very infrequent cause of microcalcifications in
      mammography.
AB  - We report a case of Klippel-Trenaunay syndrome which was suggested by
      microcalcifications detected on routine mammograms. Based on mammographic
      findings subcutaneous localization was suspected and a skin with subcutaneous
      cellular tissue biopsy was performed, confirming the microcalcifications at this
      level. The anatomopathologic report consisted of increase in vascularization in
      the subcutaneous adipose tissue due to capillary and small-venule proliferation,
      with intramural calcium deposits.

PMID- 9000414
TI  - Gadolinium-ethoxybenzyl-DTPA as a hepatobiliary contrast agent for use in MR
      cholangiography: results of an in vivo phase-I clinical evaluation.
AB  - The purpose of this study was to investigate the time course of contrast
      enhancement in bile ducts and the gallbladder (GB) after injection of gadolinium
      ethoxybenzyl-DTPA (Gd-EOB-DTPA). In a clinical phase-I study, MR imaging at 1.5T
      was performed in 16 healthy volunteers with four different doses of Gd-EOB-DTPA
      (10, 25, 50, and 100 micro;mol/kg b. w., four volunteers per dosage). The study
      protocol comprised a heavily T1-weighted fast multiplanar gradient-echo (GE)
      sequence before and at increasing intervals for up to 360 min after injection of
      Gd-EOB-DTPA. The signal enhancement was evaluated in extra- and intrahepatic bile
      ducts as well as in the GB. In all 16 volunteers the common bile duct showed
      intense signal enhancement beginning 5-16 min after injection (mean 10 min) and
      persisting for at least 120 min in 4 subjects and for 360 min in 12 subjects. The
      duration of signal enhancement was significantly (p < 0.05) longer for higher
      doses (50, 100 micro;mol/kg) than for lower doses (10, 25 micro;mol/kg).
      Intrahepatic bile ducts were hyperintense as compared with liver parenchyma in
      all subjects receiving 10 micro;mol/kg from approximately 50-120 min after
      contrast agent application. Intrahepatic bile ducts were not displayed using the
      higher doses, probably because of the strong enhancement of the liver parenchyma.
      Gallbladder contrasting was achieved in all cases beginning 7-33 min after
      injection (mean 19 min) and remained visible for up to 360 min in 94 %.
      Hyperintense visualization of normal extrahepatic bile ducts as well as the GB is
      regularly achieved with the hepatobiliary contrast agent Gd-EOB-DTPA. The dosage
      for hyperintense visualization of intrahepatic bile ducts is 10 micromol/kg.

PMID- 9000415
TI  - Problems of the Polish radiology in light of anticipated changes in the system of
      financing and organisation of the health care.
AB  - The present condition of radiology in Poland is evaluated. The main issues are
      the organisation, equipment and system of undergraduate and postgraduate training
      in radiology. The positive phenomena such as integration of all imaging
      techniques, good training of radiologists in the area of conventional radiology,
      establishing a number of modern imaging centres and lively international
      contacts, are presented. In light of anticipated changes in the organisation and
      financing of the health care as well as the possibility of increasing the
      integration of the Polish radiology with the European system of health care, the
      following seems advisable: reducing the exposure of the population to X-rays,
      prompt replacement of X-ray units which have been in use for over 15 years,
      improved effectiveness and modernization of postgraduate training in radiology
      and improved organisation of work, especially proper utilisation of the
      equipment.

PMID- 9000416
TI  - A molecular view of proximal tubular inorganic phosphate (Pi) reabsorption and of
      its regulation.
AB  - In recent years, two mammalian proximal tubular brush border membrane Na/Pi
      cotransporters (types I and II) have been structurally identified by expression
      cloning techniques. Oocyte expression studies have shown that only the transport
      characteristics of the type II transporter correspond to the well-known
      properties of proximal tubular brush border membrane of Pi transport. In studies
      on physiological regulation by hormonal and non-hormonal factors a direct
      involvement and determining role of the type II transporter has been documented.
      Most interestingly, specific membrane retrieval/insertion phenomena participate
      in acute (minutes/hours) adjustments of brush border membrane Na/Pi cotransport
      rates; for chronic (hours/days) alterations also specific resynthesis/degradation
      processes participate. In pathophysiological alterations (e.g. in X-linked
      hypophosphataemia and in heavy metal-induced nephrotoxicity) the expression of
      the type II Na/Pi cotransporters is reduced and explains the observed
      phosphaturia.

PMID- 9000417
TI  - The sustained inward current in sino-atrial node cells of guinea-pig heart.
AB  - Single myocytes were dissociated from the sino-atrial (SA) node of guinea-pig
      hearts. Only a quite small fraction of the cell population showed spontaneous
      action potentials and these cells were characterized by the presence of the
      hyperpolarization-activated cation current If , the delayed rectifier K+ current
      IK and the L-type Ca2+ current ICa,L as well as by the absence of both the
      transient outward current Ito and the inward rectifier K+ current IK, 1. After
      blocking If and IK, depolarizing pulses from -80 mV revealed a large nicardipine
      sensitive late current (NSLC). The NSLC was scarcely affected by decreasing
      extracellular [Ca2+] ([Ca2+]o) from 1.8 to 0.1 mM, while it was decreased
      significantly by depleting [Na+]o, differently from ICa,L. NSLC was blocked by
      nicardipine and was increased by Bay K 8644. NSLC was increased by isoprenaline
      and the additional application of acetylcholine reversed the increase of this
      current. We conclude that NSLC is largely composed of Ist described in the rabbit
      SA node pacemaker cells, and that Ist is unique for the pacemaker cells in
      mammalian SA node cells. Most of the quiescent cells showed neither If nor Ist.

PMID- 9000419
TI  - A large-conductance voltage-dependent potassium channel in cultured pig articular
      chondrocytes.
AB  - The patch-clamp techniques were used to study voltage-dependent potassium
      channels in cultured pig articular chondrocytes. A predominant single-channel
      conductance of 125 pS was found. These channels were reversibly blocked by
      tetraethylammonium. In cell-attached patches, transient increases in the channel
      activity were observed, and defined as a switching between low and high activity
      modes (LAM and HAM). Open-time distributions could be described with two kinetics
      components (in LAM and HAM) having similar time constants (fast tau1 and slow
      tau2). In HAM, the area of the slow component was larger. The mean burst length
      was significantly longer in HAM than in LAM. In both modes, the burst-length
      distributions were fitted with a sum of three exponentials. In LAM and HAM, the
      time constants tau1 and tau2 were indistinguishable from those of the open-time
      distributions. The slowest time constant, tau3, was strongly voltage dependent,
      and was significantly longer in HAM than in LAM. In both LAM and HAM, the
      ensemble currents were characterised by a rapid rising phase followed by fast and
      profound inactivation. The activation kinetics were similar, but the inactivation
      was faster in HAM. In the outside-out configuration no evidence for mode
      switching was found. The kinetics of the rising phase of the ensemble currents
      were also similar to those observed using the cell-attached configuration, but
      the channels did not inactivate. In the whole-cell configuration, the mode
      switching was not present. The inactivation time constant showed a large
      scattering, and was much slower than that measured in the cell-attached patch
      mode. These currents were blocked by tetraethylammonium and 4-aminopyridine. Our
      results indicate that intracellular factors are involved in controlling the mode
      switching and the kinetics of the inactivation of potassium channels in pig
      articular chondrocytes.

PMID- 9000418
TI  - Cytoplasmic Ca2+ gradients evoked by acetylcholine and peptides in pancreatic
      acinar cells of the guinea-pig.
AB  - Cytoplasmic Ca2+ levels ([Ca2+]i) in guinea-pig pancreatic acinar cells
      stimulated with acetylcholine (ACh) as well as cholecystokinin octapeptide (CCK
      8), its analogue CCK-JMV-180, bombesin and substance P (SP) have been compared by
      confocal Ca2+ imaging. We found that at intermediate and high concentrations all
      agonists evoked [Ca2+]i waves emanating from the secretory pole of the cell. The
      [Ca2+]i gradients evoked by ACh and SP were often unidirectional whereas CCK-8-
      and bombesin-elicited [Ca2+]i responses consisting of [Ca2+]i waves were normally
      followed by a secondary phase with reversed [Ca2+]i gradients. At low agonist
      concentrations the [Ca2+]i responses appeared diffuse or localized to the
      granular part of the cells. The lag times to the [Ca2+]i rises were shorter in
      response to ACh and SP than for other peptides. Thus, we found that agonists
      induced different spatio-temporal patterns of Ca2+ waves in pancreatic acinar
      cells of the guinea-pig. The reactions evoked by SP and bombesin resembled those
      evoked by ACh and CCK-8, respectively.

PMID- 9000420
TI  - Two-sided action of protons on an inward rectifier K+ channel (IRK1).
AB  - A cloned inwardly rectifying potassium channel, IRK1, expressed in Xenopus
      oocytes was found to be sensitive to an extracellular acidic pH level of below 6,
      achieved by buffering with a membrane-impermeable buffer, phthalate. The voltage
      dependency of the suppressive effect of pH on the macroscopic current suggested
      that the location of the proton-sensitive site was at approximately 5% of the
      distance from the outer entrance to the pore. The single-channel conductance was
      reduced by protonation of the channel on the extracellular side. The external
      proton-binding site appears to consist of a single class of negatively charged
      groups with a pK of around 4.6. An intracellular acidic pH, buffered with
      membrane-permeable acetate, was found to inhibit, in a voltage-independent
      manner, the macroscopic IRK1 current with an approximate apparent pK of 5.6 and
      an approximate apparent Hill coefficient of 2.3. The single-channel activity was
      abolished by intracellular acidification down to pH 5.0.

PMID- 9000421
TI  - Digitalis-like compounds and Na+, K+-ATPase activity in bovine lens.
AB  - Digitalis-like compounds in bovine lens capsule, cortex and nucleus were
      determined quantitatively, following extraction, by their ability to inhibit
      [3H]ouabain binding to red blood cells. These compounds were found to be highly
      concentrated in the epithelium capsule and were significantly diminished in the
      cortex and nucleus. Na+, K+-ATPase density in the different regions was
      determined by [3H]ouabain binding to membranes and by autoradiography of lens
      slices. The highest concentration of [3H]ouabain-binding sites was observed to
      occur in membranes prepared from the epithelial cells of the capsule, and was
      almost 100- and 200-fold higher than the concentrations observed in membranes
      prepared from fiber cells of the cortex and nucleus, respectively. In the
      autoradiography studies, strong labeling of [3H]ouabain appeared in the
      epithelial cell zone, and only weak specific labeling appeared in the lens cortex
      and nucleus. Almost all (99%) of the Na+,K+-ATPase specific activity was found to
      be in the capsule epithelium and only 0.5% was measured in the cortex and no
      activity was detected in the nucleus. These results indicate that the digitalis
      like compounds and Na+, K+-ATPase are concentrated in the lens capsule epithelium
      and are present only at low levels in the cortex and nucleus, thus implying that
      the lens capsular epithelial layer is the major region of the lens responsible
      for the homeostasis of ions and water in this tissue.

PMID- 9000422
TI  - Developmental changes of the ultrarapid delayed rectifier K+ current in rat
      ventricular myocytes.
AB  - Recent studies have shown the presence of a 4-aminopyridine (4-AP) sensitive,
      ultrarapid delayed rectifier K+ current (IK,ur) in adult human atria, but an
      apparent absence of this current in adult human ventricles. The present
      experiment was designed to investigate the postnatal changes of IK,ur in rat
      ventricular myocytes. The presence of IK,ur was evaluated with the use of a low
      concentration of 4-AP (50 micro;M). In 3-day-old newborns, the channel activity
      of rapidly activating outward current was predominantly the transient outward
      current (Ito). IK,ur could be recorded in a small number of 3-day-old cells
      lacking Ito (16%). In 10-day-old and adult rat ventricular myocytes, almost all
      cells expressed Ito and its current density increased significantly with age. The
      fraction of cells expressing IK,ur dramatically decreased with age and no IK,ur
      like component could be detected in the adult cells. These findings first
      demonstrate that the expression of IK,ur is regulated developmentally in
      mammalian ventricular myocytes.

PMID- 9000423
TI  - Enhancement of ATP-activated current by protons in dorsal root ganglion neurons.
AB  - The effect of pH on ATP-activated current in bullfrog dorsal root ganglion
      neurons was studied using the whole-cell patch-clamp technique. ATP-activated
      current amplitude was highly dependent upon extracellular pH. An acid pH
      increased, whereas alkaline pH decreased, ATP-activated current amplitude. The
      half-maximal pH (EC50) for potentiation of 2.5 micro;M ATP-activated current was
      7.2. Acidification alone did not activate detectable current and, at an acid pH,
      ATP-activated current was abolished by suramin. Proton-induced enhancement of ATP
      activated current was not sensitive to membrane potential between -80 and +40 mV,
      and did not involve a shift in reversal potential. Lowering pH from 7.2 to 6.5 or
      elevating pH from 7.2 to 8.0 shifted the ATP concentration/response curve to the
      left or right, respectively, without changing the maximal response to ATP.
      Protons increased the time constant of deactivation without affecting the time
      constant of activation or desensitization of ATP-activated current. Alteration of
      patch-pipette (intracellular) pH did not affect the enhancement of ATP-activated
      current by extracellular protons. Diethylpyrocarbonate (DEP), dithiothreitol
      (DTT), 5, 5'-dithio-bis-(2-nitro-benzoic acid) (DTNB), or N-ethylmaleimide (NEM)
      did not affect enhancement of ATP-activated current by protons. The results
      suggest that extracellular protons, at physiological concentrations, can regulate
      the function of P2X purinoceptors by modulating the affinity of the ATP-binding
      site.

PMID- 9000424
TI  - The peptide "FRCRCFa", dialysed intracellularly, inhibits the Na/Ca exchange in
      rabbit ventricular myocytes with high affinity.
AB  - We investigated the effect in rabbit ventricular myocytes of "FRCRCFa", a newly
      developed peptide inhibitor of the Na/Ca exchange. Myocytes were whole-cell patch
      clamped and experiments were carried out at 36 degrees C. The Na/Ca exchange was
      measured selectively, by blocking interfering ion channel currents and the Na/K
      pump, as the membrane current which could be inhibited by 5 mM nickel (Ni; a
      known blocker of the Na/Ca exchange). Increasing concentrations of FRCRCFa
      dialysed into the cell from the patch-pipette inhibited the Na/Ca exchange
      current. The dose/response curve could be fitted by a function for co-operative
      ligand binding, which predicted a KD for FRCRCFa-mediated inhibition of 22.7 +/-
      3.7 nM, with a Hill coefficient of 0.61 +/- 0.06. Pipette FRCRCFa concentrations
      of 1 micro;M and above were sufficient to cause complete inhibition of Na/Ca
      exchange current. The inhibitory effect of FRCRCFa was independent of membrane
      potential and relatively selective: 10 micro;M FRCRCFa dialysed into the cell had
      no effect on the L-type Ca current and delayed rectifier and inward rectifier K
      currents. Thus FRCRCFa appears to be a potent and relatively selective inhibitor
      of the Na/Ca exchange in intact cardiac myocytes, and may be of value for studies
      of the Na/Ca exchange.

PMID- 9000425
TI  - Role for protein kinase in Ca2+-dependent feedback modulation of divalent cation
      influx in internal-Ca2+-store-depleted rat parotid gland cells.
AB  - Divalent cation (Ca2+ and Mn2+) influx, stimulated by internal Ca2+ store
      depletion, into rat parotid acinar cells is inhibited by conditions which
      increase protein phosphorylation [T. Sakai and I.S. Ambudkar (1996) Am J Physiol
      271:C284-C294]. The present study examines the involvement of this protein
      phosphorylation and Ca2+ in the store-dependent inactivation of divalent cation
      entry. Internal Ca2+ store depletion, achieved by incubation (30 min) of cells in
      nominally Ca2+-free medium containing either carbachol or thapsigargin,
      stimulated Ca2+, and Mn2+, influx into cells. In either case, inclusion of 1.5 mM
      Ca2+ for the last 5 min of incubation resulted in a decrease in Ca2+ (33-41%) and
      Mn2+ (50%) influx, which could not be accounted for by internal Ca2+ store
      refill. The inhibition was prevented when internal-store-depleted cells were
      treated (prior to incubation with Ca2+) with either staurosporine or K-252a, but
      not with H-7 or KN-93. Refilling of internal Ca2+ store(s) in carbachol-treated
      cells (incubation with Ca2++atropine) induced complete inhibition of divalent
      cation influx, which was not prevented by treatment with protein kinase
      inhibitors. These data suggest the staurosporine-sensitive (and K-252a-sensitive)
      protein phosphorylation is not involved in Ca2+-store-refilling-dependent
      inactivation of Ca2+ influx but mediates a Ca2+-dependent feedback modulation of
      divalent cation influx in rat parotid gland acinar cells.

PMID- 9000426
TI  - Differential effects of a K+ channel agonist and Ca2+ antagonists on myosin light
      chain phosphorylation in relaxation of endothelin-1-contracted tracheal smooth
      muscle.
AB  - Smooth muscle contraction and relaxation are generally considered to be
      associated with phosphorylation and dephosphorylation of the 20-kDa regulatory
      myosin light chain (LC20). Thus, contractions of lamb tracheal smooth muscle
      induced by Bay K 8644 and relaxed by calcium channel blockers (verapamil, D-600
      and nitrendipine) are accompanied by an increase and decrease, respectively, of
      LC20 phosphorylation. Similarly, endothelin-1 (ET-1) induces a sustained
      contraction, which is coupled with elevated LC20 phosphorylation and reversed by
      LC20 dephosphorylation after application of a potassium channel agonist (EMD
      52692). In contrast, calcium channel blockers relax ET-1-induced contraction
      without any dephosphorylation of myosin light chains (MLC), suggesting that MLC
      phosphatase is inhibited in this case. Obviously, MLC dephosphorylation is not a
      prerequisite for smooth muscle relaxation. The variable relationship between MLC
      phosphorylation and force during relaxation suggests that there are mechanisms
      other than MLC phosphorylation that are important for regulation of contraction
      and relaxation in smooth muscle.

PMID- 9000427
TI  - Local anesthetics inhibit receptors coupled to phosphoinositide signaling in
      Xenopus oocytes.
AB  - Effects and the mechanism of action of quaternary amine local anesthetics on
      ligand- and voltage-activated ion currents were studied using voltage-clamped
      ovarian follicles and oocytes from Xenopus laevis. The fast inward and slow
      outward currents in response to acetylcholine were unaltered by procaine, whereas
      the oscillatory and smooth inward chloride currents (ICl) were abolished.
      Potassium currents (IK) elicited by norepinephrine and oscillatory ICl elicited
      by lysophosphatidic acid were blocked. Procaine caused a noncompetitive
      inhibition of oscillatory ICl mediated by heterologously expressed
      neurotransmitter receptors from the rat brain. Threefold differences were found
      in the procaine sensitivity of the 5-HT2a and 5-HT2c receptors. The rank order of
      intrinsic inhibitory activity of local anesthetics was: procaine > lidocaine >
      dibucaine > tetracaine. Extra- or intracellular application of procaine did not
      alter the Ca2+-activated Cl- current, indicating that neither the endogenous
      voltage-gated Ca2+ nor the Ca2+-activated Cl- channels account for the
      inhibition. Procaine caused only a slight reduction in ICl elicited by photolysis
      of caged inositol 1,4,5-trisphosphate (InsP3) and did not abolish ICl triggered
      by GTP[gamma-S]-induced direct activation of G proteins. For receptors coupling
      to the phosphoinositide/Ca2+ signal transduction pathway, the primary and
      physiologically relevant site of procaine action appears to be on the
      extracellular surface, upstream from the G protein, presumably on the receptor.

PMID- 9000429
TI  - Characteristics of albumin binding to opossum kidney cells and identification of
      potential receptors.
AB  - Albumin re-absorption in the kidney proximal tubule may be pathophysiological in
      disease. Opossum kidney (OK) cell monolayers were used to investigate the
      characteristics of [125I]-labelled albumin binding at 4 degrees C. Two binding
      sites were identified, one with high affinity (KD 154.8 +/-7 mg/l) and low
      capacity, the other with low affinity (KD 8300 +/- 1000 mg/l) and high capacity.
      Binding was sensitive to lectins Glycine max and Ulex europaeus I, but not other
      lectins, indicating involvement of a glycoprotein(s) in the binding process.
      Binding was also sensitive to a number of agents known to inhibit binding to
      scavenger receptors. [125I]-Labelled albumin ligand blotting of OK cell membrane
      proteins identified several albumin-binding proteins with identical lectin
      affinities to those proteins mediating albumin binding to OK cell monolayers.
      These results provide initial evidence of the identity of albumin receptors in
      kidney tubules, and suggest that they may be members of the family of scavenger
      receptors.

PMID- 9000428
TI  - Local myocardial glucose uptake is proportional to, but not dependent on blood
      flow.
AB  - In nonischaemic myocardium local deoxyglucose deposition is proportional to local
      blood flow (y = 0.77x + 0.25 for normalized deoxyglucose deposition and blood
      flow). The cause for this relationship was evaluated using a mathematical model
      of (deoxy)glucose metabolism to elucidate whether differences in local
      deoxyglucose deposition are dependent on local blood flow or whether they reflect
      differences of the local metabolic rate. The axially distributed model consists
      of two blood-tissue exchange regions arranged concentrically representing the
      capillary and the extracapillary regions, the latter being a composite of the
      endothelial, interstitial and parenchymal cell regions. Exchange between the two
      model regions is described by a permeability-surface area product, consumption in
      the extracapillary region is modelled by an intraregional clearance term. Twenty
      blood-tissue exchange units are arranged as parallel pathways to account for the
      effects of flow heterogeneity and in series with a single, nonexchanging, large
      vessel segment (0.1 ml/g). Regional volumes (capillary 0.07 ml/g, extracapillary
      0.60 ml/g) and the permeability-surface area product (0.2 ml min-1 g-1) are taken
      from published sources, the local myocardial blood flow is that determined
      experimentally (between 0.1 and 2.5 ml min-1 g-1). The only free parameter in the
      model is the extracapillary clearance term (0.0275-0.102 ml min-1 g-1) which was
      used to fit the measured tissue radioactivity concentration taking the measured
      arterial concentration of 3H-deoxyglucose into account. The results obtained
      indicate that variations in local myocardial blood flow, and hence differences in
      deoxyglucose supply, can not explain quantitatively the differences in local
      deoxyglucose deposition. However, differences of the metabolic rate (0.326 versus
      0.120 micro;mol min-1 g-1) assumed to occur in parallel to the flow differences
      (1.26 versus 0.42 ml min-1 g-1) can well explain the different mean deoxyglucose
      deposition in high and low flow areas. This result supports the view that blood
      flow heterogeneity in the heart is paralleled by a spatial heterogeneity of
      glucose metabolism.

PMID- 9000430
TI  - Inhibition of the L-type calcium channel by the five muscarinic receptors (m1-m5)
      expressed in NIH 3T3 cells.
AB  - Modulation of L-type calcium channels by the five cloned muscarinic receptors was
      studied by expression of the receptors in NIH 3T3 cells. Application of
      acetylcholine (ACh) to cells transfected with m1-m5 resulted in a reduction in
      the L-type calcium current amplitude. Elevations in intracellular cAMP
      concentrations induced by 8-bromo-cAMP or forskolin resulted in no discernible
      change in the L-type calcium current. In addition, treatment with Rp-adenosine
      3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPS), a protein kinase A
      (PKA) inhibitor, had no effect on the L-type currents. Conversely, application of
      phorbol dibutyrate, an activator of protein kinase C (PKC) or 8-bromo-cGMP, an
      activator of cGMP-dependent protein kinase (PKG), reduced the calcium currents.
      Incubation of the cells with KT5823, an inhibitor of PKG, resulted in a reduction
      of the response to 8-bromo-cGMP. The ACh-induced depression of L-type calcium
      current amplitude was sensitive to pertussis toxin (PTX) in cells transfected
      with the m2 or m4 receptor subtype. The m2-muscarinic-receptor-induced inhibition
      of the L-type calcium current was attenuated by preincubation of the cells with 8
      bromo-cAMP and was unaffected by KT5823 or by calphostin C. The m1-muscarinic
      receptor-induced inhibition of the L-type calcium conductance was insensitive to
      PTX treatment. However, the m1-induced response was blocked by preincubation of
      the cells with calphostin C. The present data indicate that the m2 (and possibly
      also the m4) muscarinic receptors inhibit the L-type calcium conductance by a
      reduction in cAMP concentration and that the m1 (and possibly also the m3 and m5)
      muscarinic receptors inhibit the L-type calcium channel via activation of PKC.

PMID- 9000431
TI  - Regional differences in the regulation of intracellular sodium and in action
      potential configuration in rabbit left ventricle.
AB  - In this study we report measurements of the intracellular sodium concentration
      ([Na+]i) in cardiac myocytes isolated from sub-endocardial and sub-epicardial
      regions of the rabbit left ventricle. These measurements show that [Na+]i is
      significantly higher in sub-epicardial than in sub-endocardial myocytes both at
      rest and during steady-state stimulation at 0.5 Hz. During a 10-min rest the rate
      of fall of [Na+]i was identical in cells from the two regions but during post
      rest recovery [Na+]i rose significantly faster in sub-endocardial cells. The
      effect that this difference in sodium regulation may have on the rate of recovery
      of the calcium transient post-rest is discussed. The steady-state differences in
      [Na+]i do not appear to have the effect on contraction we would expect i.e.
      steady-state contraction is larger in sub-endocardial cells where [Na+]i is
      lower. Changes in [Na+]i brought about by altering the frequency of stimulation
      are associated with the expected changes of contraction. Action potentials were
      found to be significantly longer in sub-endocardial cells and following rest
      action potential duration was shortened although regional differences were
      maintained. No regional differences in this effect of rest or in recovery of the
      action potential post-rest were found.

PMID- 9000432
TI  - Functional expression of rat brain cloned alpha1E calcium channels in COS-7
      cells.
AB  - The properties of the rat brain alpha1E Ca2+ channel subunit and its modulation
      by accessory rat brain alpha2-delta and beta1b subunits were studied by transient
      transfection in a mammalian cell line in order to attempt to reconcile the debate
      as to whether alpha1E forms a low-voltage-activated (LVA) or high-voltage
      activated (HVA) Ca2+ channel and to examine its pharmacology in detail. alpha1E
      alone was capable of forming an ion-conducting pore in COS-7 cells. The
      properties of heteromultimeric alpha1E/alpha2-delta/beta1b channels were largely
      dictated by the presence of the beta1b subunit, which increased current density
      and tended to produce a hyperpolarizing shift in the voltage dependence of
      activation and inactivation. alpha1E/alpha2-delta/beta1b channels did not appear
      to be regulated by Ca2+-induced inactivation. alpha1E was shown to exhibit a
      unique pharmacological profile. omega-Agatoxin IVA blocked the current in a dose
      dependent manner with an IC50 of approximately 50 nM and a maximum inhibition of
      about 80%, whilst omega-conotoxin MVIIC was without effect. The 1,4
      dihydropyridine (DHP) antagonist nicardipine (1 micro;M) produced an inhibition
      of 51 +/- 7%, whereas the DHP agonist S-(-)BAY K 8644 was without effect. Our
      findings suggest a re-evaluation of the classification of the alpha1E Ca2+
      channel subunit; we propose that rat brain alpha1E forms a novel Ca2+ channel
      with properties more similar to a subtype of LVA than HVA Ca2+ current.

PMID- 9000433
TI  - Developmental change in the voltage-dependence of the pacemaker current, if, in
      rat ventricle cells.
AB  - Myocytes were isolated from newborn and adult rat ventricle. Using the whole-cell
      patch clamp, the two cell populations were compared for the presence of the
      hyperpolarization-activated pacemaker current if. As in other mammalian species,
      the threshold voltage in acutely dissociated adult rat myocytes was extremely
      negative (-113 +/- 5 mV; n=12). In contrast, threshold in newborn cells was
      relatively positive, regardless of whether measured in acutely dissociated (-72
      +/- 2 mV; n=6) or cultured cells (-70 +/- 2 mV; n=9). Current density was not
      reduced in the adult. These results suggest that with development the ventricle
      assumes its non-pacemaker function, at least in part, by a shift of the voltage
      dependence of if outside the physiological range.

PMID- 9000435
TI  - Re-evaluation of the expression of the gastric H,K-ATPase alpha subunit along the
      rat nephron.
AB  - Under normal conditions, the rat collecting duct displays an H, K-ATPase activity
      with kinetic and pharmacological properties very close to those of the gastric
      H,K-ATPase. However, whether the collecting duct H,K-ATPase and the gastric
      enzyme are identical remains controversial. Therefore, we re-evaluated the
      expression of the mRNAs encoding the gastric H,K-ATPase alpha subunit in the rat
      nephron. For this purpose, gastric H,K-ATPase mRNAs were quantitated by RT-PCR at
      the level of microdissected nephron segments using known amounts of gastric H,K
      ATPase cRNA as external standards. Results indicate that gastric H,K-ATPase mRNAs
      are undetectable (<1 copy per cell) in the glomerulus and along the proximal
      tubule, thick ascending limb of Henle's loop and collecting duct, although a
      faint expression ( approximately 400 copies per micro;g total RNA) is measurable
      in whole-kidney preparations. Gastric H,K-ATPase mRNA is also absent along the
      nephron of K-depleted rats and of rats with chronic metabolic acidosis and
      alkalosis. Taken with other data from the literature, these results suggest that
      the collecting duct of normal rats might express an H,K-ATPase similar, but not
      identical, to the gastric isoform.

PMID- 9000434
TI  - Somatostatin induces vasodilatation in the cat mesenteric artery via endothelium
      derived nitric oxide and prostaglandins.
AB  - Direct vascular effects of somatostatin (ST) were investigated in cat superior
      mesenteric artery (SMA) segments in vitro. Changes of outer diameter were
      measured at constant axial length and perfusion pressure. SMA segments in the
      resting state were not affected by ST, regardless of endothelial integrity.
      Noradrenaline-preconstricted SMA segments were dilated concentration-dependently
      by ST (EC50 10(-13) mol/l). At maximal dilatation (by 10(-11) mol/l ST) the
      preconstriction was diminished to 45 +/- 9% (P<0.001). Perfusion with Triton X
      100, or NG-nitro-L-arginine nearly abolished the ST-induced dilatation, while
      indomethacin treatment partially suppressed it. We conclude that ST dilates
      preconstricted cat SMA segments mainly via the endothelial release of nitric
      oxide, and additionally via prostaglandins.

PMID- 9000437
TI  - NGF but not NT-3 or BDNF prevents the A fiber sprouting into lamina II of the
      spinal cord that occurs following axotomy.
AB  - There is a stereotypical pattern of primary afferent terminations within the
      mature spinal cord; however, this pattern is not immutable. Peripheral axotomy
      causes A fibers to sprout into lamina II, a region from which they are normally
      excluded. We have investigated the role of neurotrophins in this response. Rats
      which had undergone sciatic axotomy were treated intrathecally with NGF, BDNF, or
      NT-3. A fibers were visualized using transganglionic labeling with cholera toxin
      B subunit; small fibers were visualized using CGRP immunostaining. NGF (12
      microg/day for 2 weeks), but not NT-3 or BDNF, prevented both the axotomy-induced
      reduction in CGRP staining within lamina II and the sprouting of A fibers into
      this region. It is likely that the prevention of A fiber sprouting is a secondary
      consequence of NGF rescuing small fibers. This effect of NGF on dorsal horn
      sprouting has implications both for our understanding of the maintenance of CNS
      connectivity and for the treatment of neuropathic pain states.

PMID- 9000438
TI  - neurogenins, a novel family of atonal-related bHLH transcription factors, are
      putative mammalian neuronal determination genes that reveal progenitor cell
      heterogeneity in the developing CNS and PNS.
AB  - We recently identified neurogenin (ngn), a neuroD-related bHLH gene, whose
      Xenopus homolog functions as a neuronal determination factor and upstream
      activator of XneuroD (Ma et al. Cell 87: 43-52, 1996). Here we identify two
      additional ngn's, ngn2 and ngn3, which together define a novel subfamily of
      atonal-related mouse genes. Comparative analysis of ngn expression indicates that
      these three genes define distinct progenitor populations in the developing CNS
      and PNS, exhibiting nonoverlapping expression in some areas and partial overlap
      in others. The expression of the ngn's spatially overlaps and often temporally
      precedes that of neuroD, suggesting that (as in Xenopus) the ngn's and neuroD
      function in a cascade. Thus, as in myogenesis, different bHLH determination
      factors may activate a common bHLH differentiation factor in different
      sublineages. The ngn's therefore represent both a family of putative mammalian
      neuronal determination genes and useful markers of the origins of neuronal
      diversity.

PMID- 9000439
TI  - Differential expression of LIM homeobox genes among motor neuron subpopulations
      in the developing chick brain stem.
AB  - During development of the chick brain stem, cranial motor neuron subpopulations
      differentiate at distinct axial levels and extend their axons along specific
      pathways into the periphery. Differences in phenotype and axonal trajectory of
      these neuronal populations might be governed by the expression of different
      repertoires of transcription factors. In 2- to 7-day chick embryos, we find that
      genes of the LIM homeobox family are expressed differentially among cranial motor
      nuclei. Whereas Islet-1 is expressed by motor neurons of all cranial nerves,
      Islet-2 is expressed only in nuclei that contain somatic motor neurons and
      transiently in a specialized population of contralateral vestibuloacoustic
      efferent neurons. Lim-3 is expressed in the hypoglossal and accessory abducens
      nuclei only, and Lim-1 and Lim-2 are not expressed by cranial motor neurons. Our
      findings are consistent with a role of these transcription factors in determining
      neuronal phenotype and axonal pathfinding.

PMID- 9000440
TI  - Intranigral transplants of fetal ventral mesencephalic tissue attenuate D1
      agonist-induced rotational behavior.
AB  - Rats were given unilateral 6-hydroxydopamine lesions and tested 4 weeks later for
      rotational behavior elicited by either systemic or intranigral injections of
      dopamine agonists. Subsequently, transplants of fetal (E14) ventral mesencephalic
      (VM) or cortical tissue were implanted into the lesioned substantia nigra and
      allowed to develop and integrate within the parenchyma of the host midbrain for a
      4-week period before rotational behavior was retested. In animals receiving
      transplants of fetal VM tissue, systemic injections of amphetamine (5.0
      mg/kg,i.p.) or the D2-agonist, quinpirole (0.2 mg/kg, s.c.), elicited rotational
      behavior that was quantitatively similar to rotational behavior observed (1)
      before animals received transplants of fetal VM tissue or (2) in animals with
      midbrain transplants of fetal cortical tissue. Intranigral administration of
      quinpirole (10.0 microg) immobilized most animals and did not elicit rotational
      behavior in any animals regardless of treatment. Rotational behavior elicited by
      systemic administration of the D1-agonist, SKF 82958 (0.01 mg/kg, s.c.), was
      slightly attenuated by VM transplants placed into the midbrain. Rotational
      behavior elicited by intranigral injections of SKF 82958 (7.5 microg) was
      markedly reduced in animals with VM transplants. These data support the
      hypothesis that midbrain D1-receptors modulate the expression of dopamine agonist
      induced rotational behavior.

PMID- 9000441
TI  - Chondroitin 4-sulfate stimulates regeneration of goldfish retinal axons.
AB  - Our previous studies demonstrated that optic nerve regeneration in the goldfish
      is accompanied by significantly enhanced axonal transport of glycosaminoglycans
      (GAGs), with a particularly large increase in the transport of chondroitin 4
      sulfate (C4S). We have further shown that inhibition of proteoglycan (PG)
      synthesis and transport with beta-xyloside impedes axonal outgrowth from
      regenerating retinal explants. These results suggest a role for PGs that contain
      C4S in the regeneration process. To begin to address the possible functions of
      C4S GAGs during regeneration of goldfish retinal axons, we evaluated the effect
      of exogenous C4S on axonal outgrowth from regenerating retina, explanted 7-14
      days after optic nerve crush. Our results indicate that exogenous C4S added to
      the culture medium potentiates axonal outgrowth on both polylysine- and LN
      containing substrata. At low C4S concentrations, this potentiation is more marked
      on substrata containing both polylysine and LN than on polylysine alone. These
      results obtained in vitro suggest that soluble C4S, whether arising after axonal
      transport and externalization or after release from nonneuronal cells, is a
      positive modulator of regenerative axonal outgrowth in vivo.

PMID- 9000442
TI  - Partial regeneration of the sciatic nerve in rats enhances motor excitability to
      magnetic stimulation.
AB  - Motor-evoked potentials elicited from transcranial magnetic stimulation were
      recorded from both cranial tibial muscles of 10 Lewis rats. One sciatic nerve was
      then transected and surgically reanastomosed and allowed to regenerate for 6
      weeks. Walking function was tested weekly using a footprint test giving a
      functional sciatic nerve index. At the end of the study motor-evoked potentials
      were again performed, as were nerve conduction velocities and supramaximal
      stimulation of operated and unoperated sciatic nerves. The nerve was evaluated
      for myelinated axon numbers. Functional sciatic index, numbers of myelinated
      axons, nerve conduction velocities, and supramaximal stimulation demonstrated the
      regenerated nerve to be functional, but to a lesser extent than the unoperated
      nerve. In all cases the amplitude of the compound muscle action potential evoked
      from transcranial magnetic stimulation of the motor cortex was greater in the
      operated motor pathway. This finding demonstrates hyperexcitability of the motor
      pathway to magnetic stimulation during peripheral nerve regeneration.

PMID- 9000443
TI  - The role of cultured Schwann cell grafts in the repair of gaps within the
      peripheral nervous system of primates.
AB  - With recent advances in cell culture techniques it is possible to isolate human
      SCs from adult peripheral nerves, expand and purify their number in cell culture,
      and construct a cellular prosthesis from the cultured cells. The current study
      was designed to ascertain whether these techniques could be used to repair
      nonhuman primate nerve injuries. In 12 adult female cynomologous monkeys, the
      musculocutaneous (msk) nerve was divided and prevented from regenerating and the
      brachioradialis nerve (brach) was exposed bilaterally (n = 24 nerves) and injured
      so that a 15-mm gap existed within the nerve. The brach nerves were either
      repaired with sural nerve autografts (n = 6), guidance channels which contained
      monkey SCs (120 x 10(6) cells/ml; n = 6), or guidance channels without SCs (n =
      6). The remaining brach nerves (n = 6) had either no injury or an injury to the
      nerve without a repair. Autologous expanded primate SCs were increased in number
      at least 10-fold over a 2-week period at which time the SC purity exceeded 99.9%.
      Monkeys in each group, including the control group, regained some degree of elbow
      flexion after 3 months despite sectioning both the mask nerve and the brach
      nerve; therefore, we were unable to determine simply on clinical grounds which
      repair was the most effective in promoting functional recovery. Brach nerves
      repaired with sural nerve grafts were superior to both the channels which
      contained SCs and empty channels in regards to the number of myelinated axons
      proximal, within, and distal to the repair site (P < 0.05). Electrophysiologic
      results closely paralleled the histologic data with evidence of reinnervation of
      the brachioradialis muscle based on the compound muscle action potential in both
      sural nerve graft and monkey SC channel repair groups.

PMID- 9000444
TI  - Presenilin-1 immunoreactivity is localized intracellularly in Alzheimer's disease
      brain, but not detected in amyloid plaques.
AB  - The identification of the cellular and subcellular regions of the Alzheimer's
      disease brain to which the presenilin-1 (PS-1) protein localizes is expected to
      contribute to an understanding of its pathophysiological role. Toward this end,
      we have derived an affinity-purified antibody to a synthetic PS-1 peptide. In
      this report, we demonstrate that this antibody, called SW2, specifically
      recognizes full-length, 47-kDa PS-1 protein from rat primary cortical neurons,
      from a human neuronal cell line, and from human brain extracts on Western
      immunoblots. Immunohistochemical analysis of postmortem brain tissue from control
      and Alzheimer's disease patients using this SW2 antibody indicates an
      intracellular localization of PS-1 immunoreactivity with prominent perinuclear
      characteristics in neurons, with staining also detected in neuritic processes.
      Despite various treatments of the tissue sections, no PS-1 immunoreactivity was
      observed in neuritic plaques, the hallmark pathological lesions of Alzheimer's
      disease. In addition, confocal microscopic analysis of immunostained cultured
      primary neurons revealed a prominent perinuclear pattern of PS-1 immunoreactivity
      consistent with vesicular localization, as well as punctate staining in neuritic
      processes.

PMID- 9000445
TI  - Fetal spinal cord transplants rescue some axotomized rubrospinal neurons from
      retrograde cell death in adult rats.
AB  - Intraspinal transplants of fetal spinal cord may contribute to recovery after
      spinal cord injury by keeping axotomized neurons alive. In this study we examined
      whether transplants rescued axotomized red nucleus (RN) neurons from retrograde
      cell death in adult rats. RN neurons were labeled by retrograde transport of
      Fluorogold (FG); 1 week later right-sided RN neurons were axotomized by left
      sided hemisection at C3-4 vertebral level, and Embryonic Day 14 spinal cord or
      gelfoam was introduced into the cavity. Additional rats received hemisection and
      a transplant of fetal spinal cord or gelfoam without FG injection. At 2 and 4
      months, the number of neurons in the magnocellular portion of the RN
      contralateral to the hemisection decreased 35-40% in rats that received gelfoam;
      mean soma area of surviving neurons decreased 40%. RN cell loss was reduced to
      20% in rats that received fetal spinal cord transplants, but the decrease in mean
      soma area was unchanged. Transplants therefore rescued about half of the
      axotomized RN neurons that otherwise would have died but did not prevent
      perikaryal atrophy. Anterograde transport of WGA-HRP injected into RN 2 months
      after transplantation showed that rubrospinal axons reached the site of injury
      but rarely entered transplants; FG injections caudal to transplants showed that
      axons of transplant neurons extended at least two segments into host spinal cord.
      Fetal spinal cord transplants may therefore contribute to locomotor recovery in
      adults with spinal cord injuries both by preventing retrograde cell death and by
      establishing novel circuits across the site of injury.

PMID- 9000446
TI  - Tumor cell endocytosis imaging facilitates delineation of the glioma-brain
      interface.
AB  - We describe a method for measuring tumor cell endocytosis in vivo and provide the
      anatomic correlate of this tumor cell function using a superparamagnetic and
      histologically detectable marker for cell uptake (MION). Rats (n = 22) were
      intrahemispherically implanted with a thymidine kinase (TK)-positive 9L
      gliosarcoma cell line, where TK served as the tumor marker. Twenty-four hours
      after intravenous injection of 10 mg Fe/kg of MION, rat brains were removed and
      underwent MR imaging ex vivo at near-microscopic resolution (isotropic voxel size
      of 86 microm, 9.4 T) prior to histologic processing. The imaging probe
      accumulated within tumor cells adjacent to the hyperpermeable tumor-brain
      interface including microscopic deposits and along finger-like invasions of the
      tumor into brain, facilitating the demarcation of the true histologic tumor
      border in three dimensions by MR microscopy. The method has potential research
      and clinical implications for delineating the tumor-brain interface prior to
      therapy and/or for providing a rational basis for imaging nanocolloid drug
      delivery to solid tumors.

PMID- 9000447
TI  - Treatment of the chronically injured spinal cord with neurotrophic factors can
      promote axonal regeneration from supraspinal neurons.
AB  - Axonal regeneration has been demonstrated by supraspinal neurons long after a
      spinal cord injury, although this potential seems limited to a few neurons in
      specific nuclear groups. Whether the regenerative response could be enhanced by
      exposure to neurotrophic factors was examined in this study. Neurons injured
      during a cervical spinal cord hemisection lesion were labeled with true blue
      (TB). Four weeks after spinal cord injury, gel foam saturated with brain-derived
      neurotrophic factor (BDNF), neurotrophin 3 (NT-3), ciliary neurotrophic factor
      (CNTF), or saline as a control was placed into the lesion cavity. The gel foam
      was replaced with fresh factor after 3 days, and 4 days later a peripheral nerve
      (PN) graft was apposed to the rostral cavity wall. Four weeks later neurons that
      grew an axon into the PN graft were labeled with nuclear yellow (NY). Cells that
      were double labeled (TB and NY) represented chronically injured neurons capable
      of axon regeneration. Cells labeled with NY only were either acutely injured
      neurons capable of axonal regrowth or uninjured neurons that had sprouted into
      the PN graft. The total number of TB/NY-labeled neurons was significantly
      increased following exposure to BDNF, NT-3, or CNTF. Specific regions most
      influenced by NT-3 and BDNF were the reticular formation and red nucleus.
      Treatment with CNTF resulted in a significant increase in most brain regions with
      a major contribution to descending pathways in the spinal cord, the motor cortex
      being the exception, with no evidence of axonal regeneration by neurons forming
      the corticospinal tract. The total number of NY-only labeled neurons also was
      significantly greater after treatment with BDNF or CNTF. These results
      demonstrate the potential to increase the regenerative response of specific
      chronically injured supraspinal neurons by application of neurotrophic factors to
      the injury site.

PMID- 9000448
TI  - Aging, metabolism, and Alzheimer disease: review and hypotheses.
AB  - Relationships are considered among aging, metabolism, and Alzheimer disease (AD).
      In particular, after 60 years, human populations show progressive age-related
      trends for increased blood glucose that are concurrent with the accelerating
      incidence of AD. The accumulation of glycated products in the AD brain, such as
      is also found in peripheral tissues during diabetes, suggests interactions of AD
      with age-related changes in metabolism. A review of 13 recent studies on AD and
      diabetes shows no consensus, although most studies indicate an apparent exclusion
      of AD and diabetes. We argue that longitudinal studies are needed to evaluate the
      possibility that an initial age-related hyperglycemic state is reversed by the
      cachexia and weight loss common to later stages of AD. A review of literature on
      chronic food restriction in rodents shows the slowing of some aspects of aging in
      the nervous system and generally supports interactions of peripheral metabolism
      with brain aging. Finally, we discuss aspects of intermediary metabolism that
      could ensue from oxidative damage to enzymes by glycation or oxidative stress
      which include excess production of ammonia from the inhibition of glutamine
      synthetase and the production of glyceraldehyde-3-phosphate, a glycating agent
      that could contribute to damage in addition to the hyperglycemic trends during
      aging.

PMID- 9000449
TI  - Morphological and immunophenotypic microglial changes in the denervated fascia
      dentata of adult rats: correlation with blood-brain barrier damage and astroglial
      reactions.
AB  - The reactions of microglial and astroglial cells to anterograde axonal
      degeneration were studied in the fascia dentata of adult rats from 1 to 42 days
      after removal of the entorhinal perforant path projection. The observations
      focused on the kinetics of glial activation in terms of induction of
      immunomolecules on the glial cells and the possible correlation between these
      changes and lesion-induced extravasation of plasma constituents. Normal and
      activated microglial cells were identified by immunohistochemical visualization
      of the constitutively expressed complement type 3 receptor (CR3/CD11b). Activated
      microglial cells were stained immunohistochemically for the inducible major
      histocompatibility complex (MHC) antigen class I and class II and the leukocyte
      common antigen LCA/CD45). Astroglial cells were identified by immunohistochemical
      staining for glial fibrillary acidic protein (GFAP). Blood-brain barrier (BBB)
      conditions were primarily evaluated by immunohistochemical staining for
      extravasated Immunoglobulin G (IgG), but also by intravenously injected
      horseradish peroxidase (HRP) and Evans Blue. Twenty-four hours after entorhinal
      cortex ablation, microglial cells in the perforant path terminal zones displayed
      an increase in CR3 immunoreactivity, changes of morphology and an induced
      expression of MHC antigen class I. At the same time there was a hitherto
      undescribed leakage of IgG through the BBB (albeit without detectable
      extravasation of HRP and Evans Blue). One day later microglial cells also
      expressed LCA, but MHC antigen class II was not induced under these degenerative
      conditions. The activation of microglial cells occurred prior to a noticeable
      hypertrophy of astroglial cells and increase in GFAP immunoreactivity, as this
      first became evident on Postlesional Day 2. From the results we conclude (1) that
      perforant path axonal degeneration induces an endothelial transcytosis of blood
      borne IgG by mechanisms which cannot be envisioned by conventional HRP tracer
      methods and (2) that the early activation of both microglial cells and astroglial
      cells is likely to be initiated and later influenced by both axonal degeneration
      and extravasated plasma constituents. The demonstration of an early induction of
      immunomolecules on activated microglial cells and extravasation of blood borne
      molecules might moreover form the basis for a correspondingly early intervention
      aiming to regulate microglial immunomolecule, cytokine, and growth factor gene
      expression in the affected areas.

PMID- 9000450
TI  - Proportions of ON-center versus OFF-center cells in retinal ganglion cells with
      regenerated axons of adult cats.
AB  - Axons of retinal ganglion cells (RGCs) of adult cats were transected and
      regenerated by the transplantation of peripheral nerves. Two months after
      transplantation dendritic arbors of RGCs with regenerated axons (r-RGCs) were
      visualized with intracellular injections of horseradish peroxidase (HRP). The HRP
      filled r-RGCs were classified as alpha, beta, gamma, or unclassified cells. The r
      RGCs were then sectioned vertically and their dendritic ramification in the inner
      plexiform layer (IPL) was examined to distinguish them as OFF- or ON-center
      cells. Seventy-nine cells extended their dendrites into either sublamina a (OFF)
      or sublamina b (ON) of the IPL. Two gamma cells spread dendrites into both ON and
      OFF sublaminae. The numbers of ON-center cells were greater than those of OFF
      center cells in three classes: 22 of 24 beta cells, 4 of 6 gamma cells, and 16 of
      18 unclassified cells. These data confirmed the predominance of ON-center cells
      among X/beta and W cells in previous physiological recordings from regenerated
      axons of r-RGCs. However, only 4 cells were ON-center among 33 r-RGCs with alpha
      cell morphology. The result apparently conflicts with the predominance of ON
      center Y cells in physiological sampling. Possible explanations for the apparent
      discrepancy are discussed.

PMID- 9000451
TI  - Antecedent tone presentation differentially alters the rate of amygdala kindling:
      continued exposure is not required for this region-specific effect.
AB  - Recently we reported that antecedent tone presentation significantly delays the
      rate of amygdala kindling when it precedes and overlaps with every kindling
      trial. The goal of the present study was to determine if there is a minimal
      number of pairings required for the tone to exert its effects or if continued
      exposure is required. To investigate this, male Long-Evans hooded rats were
      implanted with a bipolar electrode in the right amygdala and assigned to a Tone,
      No Tone, or Tone Discontinued group and kindled once daily. The Tone group was
      exposed to the auditory stimulus on every kindling trial, while the Tone
      Discontinued group received it for only the first 5 days and subsequently was
      kindled in the same manner as the No Tone group (i.e., not exposed to the tone
      while receiving the kindling stimulation). In agreement with our earlier report,
      antecedent tone presentation significantly delayed seizure progression for
      subjects kindled in the central nucleus. However, the antecedent tone also
      significantly accelerated epileptogenesis for rats kindled in the
      amygdalostriatal transition area and produced no significant difference for those
      kindled in the basolateral nucleus. Furthermore, presentation of the tone was not
      required with every kindling trial in order for these effects to be seen,
      suggesting that a critical period might exist early in the kindling process
      during which epileptogenesis is acutely vulnerable to intervention. Additional
      research is necessary to determine the nature of these interventions and what
      effects they may have on seizure genesis.

PMID- 9000452
TI  - Apoptotic death of olfactory sensory neurons in the adult rat.
AB  - Olfactory sensory neurons only live for about 1 month in most mammals. It is not
      fully understood whether the short life span of these neurons is due to necrotic
      death, or if these cells die by apoptosis. One characteristic of cells undergoing
      apoptotic cell death is internucleosomal DNA-fragmentation. We have used TdT
      mediated dUTP-digoxigenin nick end labeling (TUNEL) to detect cells undergoing
      DNA-fragmentation in situ. In the intact olfactory epithelium of adult rats a
      subpopulation of basal immature neuronal progenitor cells, as well as mature
      olfactory sensory neurons, showed DNA-fragmentation. The number of TUNEL-labeled
      neurons increased dramatically 1.5 days after transection of the fila olfactoria
      and declined to control levels by Day 4 after the injury. In order to relate DNA
      fragmentation to ultrastructural characteristics of apoptosis we modified the
      TUNEL-labeling protocol to enable studies of TUNEL-labeled cells in the electron
      microscope. This confirmed that TUNEL-labeled neurons showed morphological
      characteristics of apoptosis. The data provide evidence for apoptotic death of
      neurons in the adult mammalian nervous system. The turnover of olfactory sensory
      neurons is, at least in part, regulated by apoptosis and disruption of the
      contact with the olfactory bulb results in massive apoptotic death of neurons in
      the olfactory epithelium.

PMID- 9000453
TI  - Experimental analysis of progressive necrosis after spinal cord trauma in the
      rat: etiological role of the inflammatory response.
AB  - Progressive tissue necrosis is a unique reaction to spinal cord trauma in which
      the site of injury is gradually transformed into a large, cavity-filled lesion.
      The earliest histopathological changes after injury include a widely disseminated
      extravasation of erythrocytes and neutrophils. To test whether such an
      inflammatory reaction might initiate progressive necrosis, we examined the
      effects of the following anti-inflammatory treatments: allopurinol (Ap) to
      inhibit injury-induced xanthine oxidase, indomethacin (I) or naproxen to inhibit
      constitutive and inducible cyclooxygenase, aminoguanidine (Ag) to inhibit
      inducible nitric oxide synthase, pregnenolone (P) as a precursor steroid, and a
      bacterial lipopolysaccharide (L) to stimulate secretory activities of glial cells
      and macrophages. The spinal cord of adult rats was crushed at T8 with jeweler's
      forceps and, after 3 or 21 days of treatment, the cords were studied
      quantitatively by light microscopical image analysis. Ag, Ag+I, or Ap
      significantly reduced the size of the primary lesion at 3 days postoperatively,
      while P+L+I did so only after 21 days of treatment. A secondary lesion developed
      in the dorsal column and gradually extended for many millimeters rostral and
      caudal from the primary lesion. The size of the dorsal column lesion was
      diminished by 3-day treatment with Ap and by 21-day treatment with Ap or P+L+I,
      but Ag or Ag+I had no effect. We conclude that (a) progressive necrosis is
      initiated and maintained by inflammatory mechanisms and (b) for this reason,
      treatment with specific anti-inflammatory agents selectively attenuates various
      components of the necrotizing process.

PMID- 9000454
TI  - A quantitative immunohistochemical study of the cellular response to crush injury
      in optic nerve.
AB  - Computer-enhanced immunohistochemical techniques were applied to quantify the
      cellular response of rat optic nerve to crush injury to attain the spatial and
      temporal detail necessary for resolving trends in the process that may be
      affected by experimental therapy. Changes in the major cell populations of the
      optic nerve during 6 weeks following crush injury were analyzed using antibodies
      against beta-tubulin (TuJ1), neurofilament (8-152), glial fibrillary acidic
      protein (GFAP), galactocerebrosides (GalC), ED-1, and von Willebrand factor to
      detect the presence of axons, astrocytes, oligodendrocytes, macrophages, and
      endothelial cells. The markers for axons, astrocytes, oligodendrocytes, and
      endothelial cells decreased their activity and remained depressed in the area of
      direct mechanical injury throughout 6 weeks following crush injury. A spatial
      peak in the axonal makers TuJ1 and 8-152 at the proximal boundary of the injury
      at both 2 and 3 weeks is consistent with the idea that the injury zone is a
      barrier obstructing distal elongation of sprouted neurites. Reactive astrocytes
      were GFAP-positive in the nerve segments proximal and distal to the injury with
      marker density above 1.5 times normal at 2 and 3 weeks. GFAP appeared to be
      absent in the site of injury even at 6 weeks postinjury, as shown by both
      immunohistochemistry and Western blot analysis. ED-1-positive macrophages were
      the most numerous population in the injury site from 1 through 6 weeks with a
      peak value measured at 2 weeks. The optical density of ED-1 activity in the
      distal and proximal nerve segments was less than 20% the density in the injury at
      all measured time points.

PMID- 9000455
TI  - Differential modulation of the cholinergic phenotype of the nucleus basalis
      magnocellularis neurons by applying NGF at the cell body or cortical terminal
      fields.
AB  - Although it is well known that exogenous nerve growth factor (NGF) can
      dramatically affect the phenotype of the basal forebrain cholinergic neurons in
      normal, aged, or lesioned animals, whether its actions are restricted to the
      terminal field level of these cholinergic neurons has yet to be established. In
      most cases, NGF has been applied into the cerebroventricle space giving it access
      to both the terminal fields and somatodendritic regions. The recent demonstration
      that TrkA, the essential component of high-affinity NGF receptors, is expressed
      not only at the distal fields (terminals and distal axons) but also at the
      proximal fields (cell bodies, dendrites, and proximal axons) of the basal
      forebrain cholinergic neurons has provoked renewed interest in this problem. More
      recently, it was further demonstrated that in Alzheimer's disease (AD), the NGF
      peptide increased throughout the brain but decreased in the nucleus basalis
      magnocellularis (NBM), suggesting that there is an impaired retrograde transport
      of NGF from the cortex to the NBM. Thus, it will be crucial to clarify whether or
      not the TrkA receptors on the somatodendritic fields of the NBM cholinergic
      neurons respond to exogenous NGF in order to support the rationale for site
      directed neurotrophic factor therapy in AD or other neurological disorders. To
      clarify this issue, we delivered 2.5S purified mouse NGF locally into the cortex
      or corpus striatum adjacent to the NBM of naive and cortically devascularized
      mature male Wistar rats. The local distribution of exogenous NGF was demonstrated
      by immunohistochemical staining. In naive rats, an NGF dose of 84.00 or 16.80
      microg infused into either the cortex or the corpus striatum for 2 weeks caused
      ipsilateral hypertrophy of the cholinergic neurons of the NBM. In cortically
      devascularized animals, an NGF dose of 84.00 microg delivered into the cortex and
      84.00 microg or 16.80 microg infused into the striatum adjacent to the NBM for 2
      weeks rescued the ipsilateral cholinergic phenotype of NBM neurons of the
      basolocortical pathway from retrograde degeneration. Thus, exogenous NGF can
      affect the cholinergic phenotype of the NBM regardless of whether it is presented
      to their nerve terminal fields or their somatodendritic region. The present
      results provide new evidence that the TrkA receptors present in the
      somatodendritic region of the cholinergic neurons of the NBM are functional and
      capable of modulating neuronal phenotype in the naive and lesioned CNS, when
      applied pharmacologically.

PMID- 9000457
TI  - Special issue dedicated to Ray W. Fuller (1935-1996).

PMID- 9000456
TI  - Identification of novel variants of trkC mRNA transcripts in brain of African
      green monkeys.
AB  - The distinct biological effects of neurotrophins are mediated in part through
      their binding to the high-affinity neurotrophin receptors represented by the Trk
      family of receptor tyrosine kinases. Using the technique of reverse transcriptase
      polymerase chain reaction (RT-PCR), we cloned several partial cDNAs encoding
      trkA, trkB, and trkC from fetal brains of African green monkeys. Southern
      analysis of PCR products showed that the ventral tegmental area of adult monkey
      and ventral midbrains of fetal monkeys of E59, E81, E91, and E150 days of
      gestation expressed all three trk gene transcripts, whereas only trkB and trkC
      mRNAs were detectable in the adult substantia nigra. The nucleotide sequences of
      the cloned monkey trk cDNAs are highly homologous to their human counterparts,
      and we detected a splice variant of trkC that has recently been described in
      humans, but not in rodents. Moreover, sequencing of trkC cDNAs derived from four
      fetal monkey midbrains revealed two novel variants with single nucleotide
      substitution. A missense mutation (AAT to AGT) was identified in the codon
      corresponding to codon 361 of the deduced human TrkC sequence, converting an
      encoded Asn to Ser. The second variant involves a silent transition at the third
      nucleotide of the codon Gly 362 (GGC to GGA). Furthermore, three of the four
      potential alleles involving these two trkC variants were detected in these
      monkeys, indicating that a segregation of multiple trkC alleles occurs in a
      geographically contained population of feral monkeys.

PMID- 9000458
TI  - Steroid hormones and excitability in the mammalian brain.
AB  - Adrenocortical and gonadal steroid hormones can pass the blood-brain barrier and
      bind to intracellular receptors in the brain. In addition to steroid hormones
      binding to intracellular steroid receptors, metabolites of these steroids and
      steroid hormones produced in the brain (neurosteroids) are thought to bind to
      membrane recognition sites. Actions mediated by the intracellular receptors are
      generally delayed in onset and are of prolonged duration, whereas the hormones
      binding to membrane recognition sites induce fast effects. Both fast and delayed
      actions by steroid hormones potentially alter the electrical properties of
      neuronal membranes and thus the firing patterns of neurons carrying receptors for
      the hormones. We here review the fast and delayed actions by steroid hormones on
      single cell electrical properties in the mammalian nervous system. In general,
      fast effects by corticosteroids-presumably mediated by membrane receptors-induce
      inhibitory effects on cellular firing, although regional differences seem to
      exist. Delayed effects by corticosteroid hormones via mineralocorticoid receptors
      serve to maintain or enhance fast transmission in the brain, while modulatory
      inputs are suppressed. By contrast, corticosteroids acting through glucocorticoid
      receptors suppress transmission carried by amino acids, particularly when the
      activity is elevated in comparison to resting level; modulatory inputs are
      enhanced. Prolonged activation of glucocorticoid receptors can implicate the
      integrity of neuronal circuits by allowing considerable influx of calcium ions
      during depolarization. Of the gonadal hormones, estradiol mainly exerts
      excitatory actions, in both a rapid and a delayed mode. Progesterone on the other
      hand is predominantly inhibitory, usually with a short delay in onset. The effect
      of androgens on neuronal excitability has not yet been studied in great detail.
      Finally, neurosteroids and A-ring reduced steroids in general induce rapid
      effects on firing patterns, probably by acting on ligand gated ion channels. The
      diverse actions of steroid hormones on single cell activity have consequences for
      the excitability in local circuits in which these cells participate. This is
      illustrated in this review for two processes that depend on circuit rather than
      single cell function, i.e., long term potentiation and epilepsy. The diverging
      character of steroid hormones with regard to the time frame, space, and nature of
      their effects is also reflected in the functional processes that are linked to
      the activity of the networks responding to steroids. In this way steroid hormones
      add an essentially new aspect to the regulation of functional processes in the
      brain, during physiological conditions but also when networks are implicated
      during diseases and disorders. Future research on steroid modulation of cellular
      excitability will gain considerably from attempts to either link the changed
      excitability to the underlying molecular events or study the effects on cellular
      activity in close connection with behavioral functions.

PMID- 9000459
TI  - 11beta-Hydroxysteroid dehydrogenase in the brain: a novel regulator of
      glucocorticoid action?
AB  - Corticosteroids (glucocorticoids and mineralocorticoids) have multiple actions in
      the brain which are mediated via specific intracellular receptors. Recently, a
      novel and important control of glucocorticoid action has been identified in
      peripheral tissues; prereceptor metabolism by 11beta-hydroxysteroid dehydrogenase
      (11beta-HSD). This enzyme catalyses the conversion of the active glucocorticoids
      corticosterone and cortisol to inert 11 keto-products (11-dehydrocorticosterone,
      cortisone), thus regulating access of glucocorticoids to receptors. Two distinct
      isozymes occur. 11beta-HSD-1 is a widespread, NADP(H)-dependent enzyme, which
      shows bidirectional activity in tissue homogenates and microsomal preparations,
      but may predominantly function as an 11beta-reductase (regenerating active
      glucocorticoids) in intact cells. 11beta-HSD-2 is a much higher affinity, NAD
      dependent, exclusive 11beta-dehydrogenase (glucocorticoid inactivating enzyme),
      which, when colocalized with otherwise nonselective mineralocorticoid receptors
      (MR), ensures selective access for aldosterone in vivo. Accumulating evidence
      indicates widespread expression of 11beta-HSD-1 in the brain. The highest levels
      are found in cerebellum, hippocampus, cortex, and pituitary, but detectable
      activity is also present in the hypothalamus (including the paraventricular
      nucleus) and other regions of neuroendocrine interest. 11beta-HSD-1 protein has
      been detected on Western blots of brain and immunostaining is widespread,
      localized predominantly in neurons and their processes. The mRNA encoding 11beta
      HSD-1 is also widely expressed in the brain, its distribution broadly paralleling
      enzyme bioactivity and immunostaining. 11beta-HSD-1 expression is regulated
      during late prenatal and postnatal ontogeny and by glucocorticoids and stress,
      prompting suggestions that this isoform may play a role in protecting the brain
      from the deleterious consequences of glucocorticoid excess. However, in primary
      cultures of hippocampal neurons, 11beta-HSD-1 functions as a predominant 11beta
      reductase, reactivating inert corticoids and thus potentiating neurotoxicity. The
      functions of 11beta-HSD-1 in the CNS are not defined, but may relate to mood,
      neuronal survival, and glucocorticoid feedback. The identification of aldosterone
      selective actions in the brain (upon blood pressure and salt appetite) predict
      the presence of 11beta-HSD-2. This isozyme has very limited expression in the
      adult brain, probably confined to the subregions of the brain stem and the
      subcommissural organ, where some aldosterone-selective actions may be mediated.
      However, the midgestation fetal brain highly expresses 11beta-HSD-2, which might
      modulate glucocorticoid effects on CNS development. Studies with licorice-derived
      enzyme inhibitors indicate functional effects for 11beta-HSD in the adult brain,
      notably in the periventricular hypothalamus and limbic system. Thus, 11beta-HSD
      represents a novel and potentially important level of control of glucocorticoid
      action in the CNS. Enzyme modulation by pharmacological or other agents may
      provide a useful means to target increased or attenuated glucocorticoid action to
      specific sites in the brain.

PMID- 9000460
TI  - EDITORIAL

PMID- 9000461
TI  - The neuropeptide story. Geoffrey Harris Lecture, Budapest, Hungary, July 1994.

PMID- 9000462
TI  - Influence of thyroid status on water metabolism and survival of normal and
      dehydrated desert rodents Meriones libycus.
AB  - The relationship between thyroid status and resistance to water deprivation in a
      desert rodent, Meriones libycus, has been studied in normal,
      radiothyroidectomized (Tx), and thyroidectomized T4-supplemented (1.5 microg
      T4/day) (Tx + T4) animals. In animals given free access to water, 1 month after
      thyroidectomy water influx and efflux decreased 3-fold. This decrease was
      partially corrected after 5 days of T4 administration. Thyroidectomy did not
      modify urinary osmolality nor affect survival. In dehydrated animals, the body
      weight decreased (about 15%) over 2 weeks in all groups and then stabilized.
      Water flux decreased sharply in normal or Tx + T4 animals during the 1st week and
      then stabilized. A further decrease of water flux occurred in hypothyroid
      animals, which continued over 4 weeks, when fluxes were half those of normal or
      Tx + T4 animals. The urinary osmolality increased equally sharply in the three
      groups, at least during the first 5 days of dehydration when sampling was
      possible. Whereas dehydrated normal and Tx + T4 animals survived at least 7
      weeks, 70% of Tx animals had died after 4 weeks and none survived more than 7
      weeks. The daily metabolic energy intake was estimated from water flux and
      metabolic water of the dietary barley. After 4 weeks, when water influx
      represented only metabolic water from food, metabolic energy intake decreased 2.5
      fold in hypothyroid compared with normal or Tx + T4 animals. This low metabolic
      energy intake led to a trend of body dehydration, hypothermia, and death. Thus,
      although an effect of thyroidectomy on survival of hydrated animals beyond 4
      weeks cannot be excluded, we infer that thyroid hormones play a significant role
      in the survival of desert rodents under conditions of hydric stress.

PMID- 9000463
TI  - The presence of angiotensin II receptors in elasmobranchs.
AB  - The presence of specific Ang II receptors in membrane fractions was investigated
      using 125I-labeled homologous Ang II ([Asn1, Pro3, Ile5]Ang II; df Ang II) in
      Triakis scyllia. Specific binding sites occurred in a variety of tissues, with
      highest binding in interrenal tissue (17.11 +/- 2.45 fmol Ang II/mg protein) and
      gill (6.26 +/- 0. 69 fmol Ang II/mg protein) and possible Ang II receptors in
      rectal gland and other tissues. 125I-[Asn1, Pro3, Ile5]Ang II (10(-10)M) binding
      to branchial cell membrane fraction (25 microg protein) in 5 mM MgCl2, 125 mM
      NaCl, 50 mM Tris-HCl, 0.2% bovine serum albumin at 28 degrees (1) is rapid and
      saturable; (2) increases as a function of membrane concentration and time; and
      (3) optimally fits to a two-site (high-and low-affinity) model. The equilibrium
      dissociation constant (0.11 +/- 0.01 nM) and binding site concentration (35.00 +/
      1.16 fmol/mg protein) are similar to those of mammalian and avian vascular Ang
      II receptors. Bound labeled ligand was not competitively displaced by dogfish Ang
      I, dogfish C-type natriuretic peptide, bradykinin, or the AT1 receptor
      antagonist, CV 11974. The AT2 receptor antagonist, CGP 42112, was much less
      potent at displacing the labeled ligand compared to the unlabeled ligand.

PMID- 9000464
TI  - Interrenal function in larval Ambystoma tigrinum. IV. Acid-base balance and the
      renin-angiotensin system.
AB  - Larval Ambystoma tigrinum were cannulated nonocclusively in the truncus
      arteriosus and allowed to recover for 20-24 hr. In one group of animals a
      peritoneal cannula was inserted in order to induce acidosis through the injection
      of lactic acid (2 micromol/g). Immediately following a control blood sample (hr
      0), lactic acid was injected, and blood samples were collected at 1, 4, 8, and 24
      hr and analyzed for pH, PCO2, PO2, [HCO3-], and aldosterone. These animals
      exhibited a significant metabolic acidosis, which was accompanied by a
      significant increase in plasma aldosterone, and recovered in approximately 24 hr.
      Additional groups of animals were subjected to the same acidosis and also
      received either saralasin (0.01 or 1 microg/g at 0, 1, and 4 hr) or captopril
      (0.01-0.1 or 1 microg/g at 0, 1, and 4 hr). The groups of animals whose renin
      angiotensin system was blocked by saralasin or captopril did not show a
      significant change in their ability to recover from the metabolic acidosis.
      Furthermore, saralasin and captopril were ineffective in inhibiting the normal
      rise in circulating aldosterone in response to acidosis. In another group of
      animals, synthetic human angiotensin II (1 microg/g; Ang II) was infused
      immediately following the control blood sample (hr 0) and blood samples were
      collected at 2, 4, 6, and 8 hr and assayed for aldosterone. Plasma aldosterone
      levels increased significantly from 133 +/- 91 pg/ml at hr 0 to a maximum of 3288
      +/- 519 pg/ml at hr 4. Sham-treated animals did not increase circulating
      aldosterone. When Ang II (1 microg/g) and saralasin (1 microg/g) were given
      simultaneously, however, the rise in plasma aldosterone was only about 35% that
      of animals which received Ang II alone. We conclude that administration of Ang II
      leads, either directly or indirectly, to synthesis and release of aldosterone
      from the interrenal tissues of larval Ambystoma tigrinum and that this rise can
      be significantly attenuated by saralasin. We furthermore conclude that although
      the renin-angiotensin system may be indirectly involved in recovery from an acid
      challenge, it does not appear to be the stimulus for the observed increase in
      plasma aldosterone in response to acidosis in these animals.

PMID- 9000465
TI  - Tissue-specific alterations in insulin-like growth factor-I concentrations in
      response to 3,3',5-triiodo-L-thyronine supplementation in the growth hormone
      receptor-deficient sex-linked dwarf chicken.
AB  - Insulin-like growth factor-I (IGF-I) mediates many of the effects of growth
      hormone (GH). The regulation of IGF-I, independent of GH, is methodologically
      difficult to assess in vivo, as hypophysectomy results in derangement of many
      pituitary hormone axes in addition to GH, and a gene knockout model is not
      available. The recessive sex-linked dwarfing (SLD) gene (dw) in chickens results
      in a lack of functional target tissue GH receptors due to a variety of molecular
      defects, which provides a unique model for evaluating GH-independent regulation
      of IGF-I. In the present study, the impact of 3,3', 5-triiodo-l-thyronine (T3) on
      circulating and tissue IGF-I was determined in normal versus SLD birds. Adult,
      nonovulatory female normal and SLD chickens were restrict-fed 40 g of feed/kg
      bw/day containing 0, 0.5, or 1.0 ppm T3, resulting in supplementation levels of 0
      (control), 20 (low dose), or 40 (high dose) microg T3/kg bw/day for 10 days.
      Samples of GH target tissues including liver, abdominal fat pad, skeletal muscle
      (pectoralis major), and spleen were extracted and assayed for IGF-I. Plasma T3,
      T4, GH, and IGF-I were determined by homologous RIA. Tissue GH binding was
      determined for hepatic membranes by radioreceptor assay. Under control
      conditions, dwarf chickens were markedly hypersomatotropic (33.3 +/- 4.1 ng GH/ml
      plasma; mean +/- SEM) compared to normals (2.4 +/- 3.9 ng/ml), and T3
      supplementation reduced this to normal levels. Despite the high circulating level
      of GH in dwarfs, plasma IGF-I was low compared to normal controls (dwarfs 1.5 +/-
      .9 ng/ml; normals 5. 3 +/- .9 ng/ml; P = 0.004), but this difference was
      eliminated with low-dose T3. In this study, tissue IGF-I was undetectable in
      liver and pectoralis muscle in adults (55 weeks of age) of both genotypes, under
      all treatments. In contrast, adipose tissue IGF-I was relatively high and did not
      differ (P = 0.84) between genotypes under control conditions (normals 776.5 +/-
      236.7; dwarfs 844.6 +/- 236.7 pg/mg protein), but was increased in normals and
      decreased in dwarfs, resulting in higher levels (P = 0.02) in the normal (1249.9
      +/- 200.0 pg/mg protein) than in the dwarf genotype (558.4 +/- 200.0 pg/mg
      protein) at the higher level of T3 supplementation. This relationship was
      somewhat reversed in spleen, where T3 tended to decrease tissue IGF-I
      concentration in normals and increase it in dwarfs. The low level of plasma IGF-I
      despite nonmeasureable hepatic IGF-I tissue concentrations suggests that IGF-I
      synthesis by extrahepatic tissues contributes to the circulating pool of IGF-I.
      The relatively high control levels of adipose tissue IGF-I in the dwarf genotype
      further suggest that considerable IGF-I synthesis exists that is GH-independent
      in this extrahepatic tissue. The presence of GH action, however, may mediate the
      effects of other hormones that can influence local IGF-I production in this
      tissue, as reflected by the differential response to T3 supplementation between
      genotypes. The tissue-specific nature of the effect of T3 on IGF-I production
      supports an additional point of regulation of hormone action at the target tissue
      level.

PMID- 9000466
TI  - Proliferative effect in vitro of follicle-stimulating hormone on the left ovary
      of the chick embryo.
AB  - The purpose of the present study was to evaluate the effect of human follicle
      stimulating hormone (hFSH) on cellular proliferation in the chick embryo ovary.
      Left ovaries from 18-day-old chick embryos (Babcock B300) were dissociated by
      trypsin (0.25%) treatment. In some experiments, dissociated ovarian cells were
      further separated by a continuous metrizamide gradient (0-20%). Four cellular
      subpopulations were recovered from the density gradient: (a) typical
      steroidogenic cells (F1, density 1.026 g/ml), (b) primary oocytes (F2, 1.048
      g/ml), (c) pregranulosa cells, and (d) poorly differentiated epithelial cells
      (both cellular types were found in F3, 1.059 g/ml, and F4, 1.071 g/ml). Samples
      (5 x 10(5) cells) of dissociated cells of the whole ovary and of the four
      cellular subpopulations obtained from the density gradient were cultured on
      polycarbonate membranes in a defined medium with 0.1 microCi of [3H]thymidine for
      60 hr. When necessary, 17beta-estradiol, hFSH, recombinant human FSH, and hCG
      were added to the medium at the begining of the culture. The total number of
      cells and the incorporation of [3H]thymidine to the ovarian cell aggregate at the
      end of the culture increased when hFSH and recombinant hFSH (0.5 IU/ml) were
      added. No changes were produced with hCG (2.0 IU/ml) and 17beta-estradiol (200
      ng/ml) treatments. The secretion of 17beta-estradiol by cultured ovarian cells
      was stimulated in the hFSH-, recombinant hFSH-, and hCG-treated groups. The dose
      response curve to hFSH resulted in an ED50 of 0.03 IU/ml. In the temporal curve,
      the stimulatory effect of hFSH on the total number of cells and the [3H]thymidine
      incorporation were observed at 36 hr of culture and maintained up to 60 hr. The
      proliferative effect of hFSH measured as [3H]thymidine incorporation was observed
      only in the F4 fraction of the density gradient, which includes poorly
      differentiated epithelial cells and pregranulosa cells from the ovarian medulla
      and cortex, respectively. Present results demonstrate a dose-dependent
      stimulation of DNA synthesis by hFSH in the inmature ovary of the 18-day-old
      chick embryo. Either pregranulosa cells or poorly differentiated epithelial cells
      or both subpopulations would be the target cells for the proliferative effect of
      the gonadotropin.

PMID- 9000467
TI  - Use of a radioimmunoassay which detects C21 steroids with a 5beta-reduced, 3alpha
      hydroxylated configuration to identify and measure steroids involved in final
      oocyte maturation in female plaice (Pleuronectes platessa).
AB  - Two radioimmunoassays (RIAs) have been developed which detect C21 (pregnane)
      steroids with a 5beta-reduced, 3alpha-hydroxyl (5beta, 3alpha) configuration. One
      RIA only detects 3alpha,17, 21-trihydroxy-5beta-pregnan-20-one and 3alpha, 17
      dihydroxy-5beta-pregnan-20-one, whilst the other detects a range of 5beta,3alpha
      steroids, including 5beta-pregnane-3alpha,17,20 beta-triol, a major metabolite of
      17, 20beta-dihydroxy-4-pregnen-3-one, the putative oocyte maturation-inducing
      steroid in plaice Pleuronectes platessa. The RIAs, in conjunction with reverse
      phase high-performance liquid chromatography (HPLC), have identified and
      quantified the steroids in plasma and urine of reproductively mature females.
      Total levels of 5beta,3alpha metabolites which can be extracted with diethyl
      ether (i.e., free steroids) are relatively low (<10 ng/ml). However, total levels
      of 5beta,3alpha metabolites released by solvolysis (i.e. , sulphated steroids)
      are very high (up to 1000 ng/ml in plasma and 20 microg/ml in urine). On HPLC,
      these metabolites have been identified (in order of their abundance in plasma)
      as: 3alpha,17, 21-trihydroxy-5beta-pregnan-20-one, 5beta-pregnane-3alpha,17,
      20beta-triol, 5beta-pregnane-3alpha,17,20alpha-triol, 3alpha,11beta, 17,21
      tetrahydroxy-5beta-pregnane-20-one, and 3alpha, 17-dihydroxy-5beta-pregnan-20
      one. Levels of the first three steroids are significantly elevated in female
      plaice undergoing natural or gonadotrophin-induced final oocyte maturation.

PMID- 9000468
TI  - Use of a radioimmunoassay which detects C21 steroids with a 17, 20beta-dihydroxyl
      configuration to identify and measure steroids involved in final oocyte
      maturation in female plaice (Pleuronectes platessa).
AB  - A radioimmunoassay (RIA) has been developed to detect a range of C21 (pregnane)
      steroids with a 17,20beta-dihydroxyl (17,20beta) configuration. In conjunction
      with reverse-phase high-performance liquid chromatography (HPLC), it identifies
      and quantifies the metabolites of 17,20beta-dihydroxy-4-pregnen-3-one, the
      putative "maturation-inducing steroid" in female plaice Pleuronectes platessa.
      Total levels of 17,20beta metabolites which can be extracted from plasma or urine
      with diethyl ether (i.e., free steroids) are very low (<3 ng/ml). However, total
      levels of 17,20beta metabolites which can be released by solvolysis (i.e.,
      sulphated steroids) are very high (up to 1 microg/ml in plasma and 10 microg/ml
      in urine). On HPLC, these sulphated metabolites have been identified (in order of
      abundance in plasma) as: 5beta-pregnane-3alpha,17,20beta-triol, 5beta-pregnane
      3beta,17,20beta-triol, 17, 20beta-dihydroxy-4-pregnen-3-one, and 17, 20beta
      dihydroxy-5beta-pregnan-3-one. These steroids are absent from plasmas of fish
      which have not yet begun final oocyte maturation. The results support the
      hypothesis that 17, 20beta-dihydroxy-4-pregnen-3-one is the maturation-inducing
      steroid in plaice but that it is rapidly metabolised to render it inactive. The
      results also show that the '17,20beta'-RIA, in combination with an overnight acid
      solvolysis procedure, is a useful procedure for monitoring the effects of
      exogenous factors (such as gonadotrophin injections) on final oocyte maturation
      in female plaice.

PMID- 9000469
TI  - Effects of hypothalamic factors on somatolactin secretion from the organ-cultured
      pituitary of rainbow trout.
AB  - The profile of daily release of somatolactin (SL) and effects of hypothalamic
      factors on SL secretion from the organ-cultured pituitary of rainbow trout were
      examined. The daily release of SL was relatively high (340-380 ng/pituitary/day)
      for the first 2 days and then decreased. After Day 5, the SL release was
      maintained at a low level (30-50 ng/pituitary/day) until the end of the
      experiment at Day 7. The secretory patterns of SL differed from those of growth
      hormone (GH) and prolactin (PRL); GH secretion was consistently high (15-20
      microg/pituitary/day), whereas PRL secretion was low (10 ng/pituitary/day) during
      the experiment. SL release was not stimulated by calcium ionophore on Days 2 and
      6, suggesting that SL release was maximal. Dopamine and epinephrine, added
      separately to the medium, inhibited SL release. In contrast, serotonin,
      corticotropin-releasing factor, and gonadotropin-releasing hormone stimulated the
      dopamine-inhibited SL release. Thus, SL secretion is concluded to be under
      hypothalamic control and regulated by mechanisms different from those affecting
      PRL and GH secretion.

PMID- 9000470
TI  - Evolution of insulin-like growth factor (IGF) function: production and
      characterization of recombinant hagfish IGF.
AB  - While there is considerable structural evidence that insulin-like growth factors
      (IGFs) share a long evolutionary history, little is known about the conservation
      of IGF function. In order to address this, we have made recombinant hagfish IGF,
      hence allowing characterization of an IGF from a representative of the primitive
      vertebrate class, Agnatha. The production of recombinant hagfish IGF has been
      complicated by a number of factors including the requirement of a longer leader
      peptide for fusion protein expression, reduced solubility of the protein, as well
      as problems in the refolding procedure. However, we were able to produce a small
      quantity of hagfish IGF with an N-terminal glycine addition which is biologically
      active. Furthermore, N-terminal amino acid sequencing and mass spectrometry
      confirm that we have produced hagfish IGF. In vitro assessment of recombinant
      hagfish IGF in cultured cells indicates that hagfish IGF indeed shares functional
      properties with mammalian IGFs. Thus, hagfish IGF stimulates protein synthesis in
      rat myoblasts, but 20- and 5-fold more peptide, respectively, is required to
      achieve the same half-maximal responses as with human IGF-I (hIGF-I) or IGF-II
      (hIGF-II). Hagfish IGF also competes for binding to the type-1 IGF receptor
      present both on rat myoblasts and on salmon embryo fibroblasts, though with
      somewhat lower affinity than either hIGF-I or hIGF-II. However, studies
      investigating binding to the IGF-II-specific type-2 receptor suggest that hagfish
      IGF may in fact be more closely related to IGF-I than to IGF-II. These results
      indicate that motifs important for functions associated with mammalian IGFs
      appear to have evolved prior to the Agnathans diverging from the main line of
      vertebrate evolution 550 million years ago. Accordingly, we now have functional
      as well as structural evidence that the IGFs have a long evolutionary history.

PMID- 9000471
TI  - CCK-A- and CCK-B-like receptors in the gallbladder and stomach of the alligator
      (Alligator mississippiensis).
AB  - Autoradiographic analysis of radioligand binding was used to localize and
      characterize cholecystokinin (CCK) receptors expressed in the stomach and
      gallbladder of the American alligator (Alligator mississippiensis). Alligator
      gallbladder smooth muscle expresses a CCK-A receptor subtype, and stomach oxyntic
      mucosa expresses a distinct receptor subtype, termed CCK-B/X because of its
      similarities to both CCK-B and CCK-X receptors. Both the gallbladder and the
      stomach binding sites have very low affinities for a panel of nonpeptide receptor
      agonists and antagonists that are selective for mammalian CCK-A and CCK-B
      receptors. These results suggest that CCK receptor subtypes diverged from the
      ancestral CCK-X receptor in an early amniote, prior to the divergence of mammals
      and reptiles in vertebrate phylogeny, and that CCK-A receptors may have evolved
      before CCK-B receptors. Our findings support the hypothesis that the evolution of
      gastrin preceded the evolution of two separate CCK receptor subtypes.

PMID- 9000472
TI  - Reproductive endocrinology of the explosively breeding desert spadefoot toad,
      Scaphiopus couchii.
AB  - The spadefoot toad, Scaphiopus couchii, is an explosively breeding, desert
      dwelling amphibian that shows two characteristics hypothesized to select for a
      dissociated breeding pattern: it lives in a harsh environment and it has a very
      short, but predictable breeding period. We tested the hypothesis that these
      factors select for a dissociated breeding cycle by measuring plasma steroid
      hormones and the gametogenic cycles in a free-living population of S. couchii.
      Blood and tissue samples were obtained from prebreeding, calling (males only),
      amplexed, and postbreeding toads. In males, plasma testosterone (T),
      dihydrotestosterone (DHT), and corticosterone (B) differed significantly among
      reproductive groups, with calling and amplexing toads having the highest levels
      of each of these steroids. In females, plasma T, DHT, B, progesterone (P), and
      estradiol (E2) were measured; all steroids except B changed significantly among
      mating groups. Plasma T and E2 were greatest in prebreeding and amplexed females,
      while P and DHT were highest only in amplexed females. Primary spermatogonia (SPG
      I), secondary spermatogonia (SPG II), spermatocytes, spermatids (SPT), and
      spermatozoa embedded in Sertoli cells (SPS) all changed significantly among male
      breeding groups. Although all stages were present in all breeding groups, early
      stages of spermatozoa (SPG I and SPG II) were greatest in postbreeding males,
      while late stages (SPT and SPS) were highest in prebreeding, calling, and
      amplexing males. In females, oocyte stages I, II, III, V, and VI and atretic
      follicles also differed significantly among mating groups. Prebreeding female
      ovaries were dominated by late-stage (V and VI) oocytes which were subsequently
      ovulated during amplexus. In postbreeding females, oogenesis was well under way
      as indicated by the rising numbers of stage II and III oocytes. These results
      indicate that aspects of gametogenesis occur during and after breeding in both
      sexes. Although the results demonstrate that gonadal activity was high during the
      period of sexual activity, suggesting that S. couchii most closely fits an
      associated pattern of reproduction as defined by Crews (1984, Horm. Behav. 18, 22
      28), we also found that gonadal activity continued past the breeding season. For
      this reason, S. couchii does not completely conform to an associated pattern.

PMID- 9000474
TI  - Follicle and extrafollicular tissue interaction in 17alpha,20beta-dihydroxy-4
      pregnen-3-one-stimulated ovulation and prostaglandin synthesis in the yellow
      perch (Perca flavescens) ovary.
AB  - Intact (attached to extrafollicular (EF) tissue) yellow perch follicles ovulate
      in vitro when stimulated with the steroid, 17alpha, 20beta-dihydroxy-4-pregnen-3
      one (17,20-PG). However, follicles isolated from EF tissue will not ovulate under
      17,20-PG stimulation. In the present study, the interaction of follicles and EF
      tissue in 17,20-PG-stimulated ovulation and prostaglandin synthesis was
      investigated by separating follicles from EF tissue at specific times during
      incubation. Following separation, the incubation of isolated follicles and EF
      tissue was continued. At 48 hr of incubation, isolated follicles were assayed for
      ovulation and the media of isolated follicle and EF tissue incubates were assayed
      by RIA for prostaglandin E (PGE) and prostaglandin F (PGF) levels. Steroid
      stimulated follicles, isolated from EF tissue prior to 22 hr of incubation,
      ovulated less than 25%. However, there was a very large increase in the
      percentage ovulation in follicles separated from EF tissue from 24 to 32 hr. PGF
      levels increased significantly in 17,20-PG-stimulated follicles isolated from EF
      tissue after 22 hr. In contrast, mean PGE levels in steroid-stimulated follicle
      incubates appeared to be lower than control levels. Compared with controls, PGE
      and PGF levels were significantly lower in incubates of isolated EF tissue
      stimulated with 17,20-PG, and this did not appear to be related to the time of
      separation. The results demonstrate that follicles must interact with EF tissue
      for a specific length of time for ovulation and PGF synthesis to occur in
      isolated follicles. Further, the effects of 17,20-PG on prostaglandin synthesis
      appear to be specific for different tissue compartments.

PMID- 9000473
TI  - Comparison of growth factor receptors and metabolic characteristics of satellite
      cells derived from the biceps femoris and pectoralis major muscles of the turkey.
AB  - Myogenic satellite cells were isolated from the turkey pectoralis major (PM), a
      muscle composed largely of white fibers, and the biceps femoris (BF), a muscle
      composed largely of red fibers, and their properties were compared in culture.
      Satellite cells derived from the PM and BF muscles exhibited differences in
      metabolic parameters, growth factor receptor characteristics, and mitogenic
      responses. PM satellite cells exhibited greater responsiveness to platelet
      derived growth factor (PDGF), and the PDGF receptor on these cells had a higher
      affinity toward ligand compared to BF cells (P < 0.05). Protein synthesis,
      protein degradation, and glucose uptake rates were higher in BF satellite cell
      cultures (P < 0.05), correlating with previously reported in vivo measurements
      using red and white muscle fibers.

PMID- 9000475
TI  - Effects of somatolactin on melanosome aggregation in the melanophores of red drum
      (Sciaenops ocellatus) scales.
AB  - The effects of purified red drum somatolactin on pigment movement in red drum
      scales were studied in vitro and in vivo. The integument became pale within 2 min
      following an intramuscular injection of somatolactin (1 nmol/g body weight) in
      fish held in a black-background aquarium, and gradually regained its black
      coloration during the subsequent 30 min. No melanosome aggregation was observed
      in fish injected with vehicle or somatolactin over the dose range of 10(-9)-10(2)
      pmol/g. Melanosomes in the melanophores of scales were completely aggregated
      within 10 min of incubation with 1 microM somatolactin in vitro. The effect of
      somatolactin on melanosome aggregation was dose-dependent. Somatolactin caused
      only partial aggregation at a concentration of 500 nM and 250 nM somatolactin had
      little or no effect. Somatolactin caused melanosome aggregation in both
      innervated and denervated melanophores. Aggregated melanosomes which had been
      preincubated with somatolactin dispersed within 30 min after rinsing with a
      physiological buffer. No melanosome aggregation was observed in scales incubated
      with 10 nM-1 microM of red drum prolactin (PRL), red drum growth hormone (GH),
      ovine PRL, or recombinant tuna GH. These results indicate that the action of
      somatolactin on melanosome movement is direct, specific, reversible, and is
      probably mediated by a specific somatolactin receptor on the melanophores.
      Melanin-concentrating hormone (MCH) and norepinephrine (NE) also induced
      melanosome aggregation in scales at a low concentration of 10 nM. Addition of 1
      microM alpha-melanophore-stimulating hormone (alpha-MSH) following preincubation
      of scales with 1 microM somatolactin, 10 nM MCH, or 10 nM NE resulted in partial
      dispersion of the melanosomes. These results suggest that melanosome migration in
      red drum scales is under multiple hormonal control. Although a direct action of
      somatolactin on melanosome aggregation is demonstrated in this study, its
      physiological role in the regulation of this process remains unclear.

PMID- 9000476
TI  - The role of 20-hydroxyecdysone in stimulating DNA synthesis in corpora allata of
      the silkworm, Bombyx mori.
AB  - Temporal changes in DNA synthesis were examined in the corpora allata of the
      silkworm Bombyx mori during the penultimate larval stadium. 5'-Bromo-2'
      deoxyuridine (BrdU) labeling revealed that allatal DNA synthesis rose early in
      the stadium, peaking at about 2% of corpus allatum (CA) cells 24 hr after
      ecdysis. This corresponded to a rising phase of the ecdysteroid titer reported
      previously. DNA synthesis declined to a nearly undetectable level 1 day later. In
      larvae fed on leaves coated with 20-hydroxyecdysone (20E), the number of BrdU
      labeled cells increased continuously after the normal peak and reached about 8%
      of CA cells at the end of the stadium. However, total count of CA cells from
      whole-mount monolayers and colchicine treatment indicated that, regardless of DNA
      content, CA cells did not divide. To determine if the rise in 20E was responsible
      for the onset of allatal DNA synthesis, we have established an organ culture
      system to support de novo DNA synthesis in vitro. The number of BrdU-labeled
      cells increased with increasing 20E concentration between 0.1 and 0.5 microg ml-1
      in the medium, corresponding well to the rising 20E titer in the hemolymph. The
      level of DNA synthesis in culture was further elevated when 20% hemolymph was
      added together with 20E, suggesting that other direct stimulatory factors for
      allatal DNA synthesis may also exist in the hemolymph.

PMID- 9000477
TI  - Methionine enkephalin: a new cytokine--human studies.
AB  - The effects of methionine enkephalin (met-enkephalin) on human immune function
      are reviewed. This pentapeptide functions to upregulate, or enhance, immune
      function in the majority of donor samples at low doses and suppresses at high
      doses. The influence of this molecule is shared by the central nervous,
      neuroendocrine, and immune systems. Cells from each of these systems possess
      receptors for met-enkephalin and have the ability to process met-enkephalin from
      its prohormone, proenkephalin A. Studies have shown that this molecule is capable
      of enhancing immune function in patients with cancer or AIDS. It is proposed that
      this molecule be classified as a cytokine.

PMID- 9000478
TI  - Macrophages, multinucleated giant cells, and apoptosis in HIV+ patients and
      normal blood donors.
AB  - Clearance of apoptotic debris is carried out by cells of the monocyte/macrophage
      lineage and, as other macrophage functions, it can be altered in AIDS, leading to
      the accumulation of apoptotic cells observed in this disease. In this study we
      evaluated the ability of macrophages from human immunodeficiency virus (HIV)
      infected patients to differentiate and to clear apoptotic debris in prolonged in
      vitro cultures. Peripheral blood mononuclear cells (PBMC) from infected
      hemophilia patients were cultured in the absence of exogenously added stimulators
      and the organization and morphological characteristics of the cultures were
      analyzed and correlated with clinical staging of the patients. Cell aggregates of
      different sizes involving macrophages and lymphocytes were formed in cultures
      from asymptomatic HIV+ patients (CDC groups II-III) and controls and in 4/7 group
      IV C2 HIV+ patients. In order to obtain viable and organized cultures, cells had
      to be handled carefully, allowing contact and undisturbed sedimentation in round
      bottom tubes. Multinucleated giant cells (MGC) were formed through macrophage
      fusion after 5 days of culture in HIV- controls, group II and III patients, and
      some of the group IV C2 patients, while scarce formation of MGC was observed in
      AIDS patients or patients with advanced HIV disease. This paucity was correlated
      with impaired dead cell removal and accumulation of apoptotic debris. Viability
      of macrophages and MGC was reduced after 15 days. MGC and the macrophages (either
      free or in cell aggregates) were able to remove dead cells, clearing the cultures
      of cell debris. Furthermore, in group II and III HIV+ hemophilic patients,
      increased macrophage-MGC phagocytic activity, suggesting in vivo activation, was
      frequently observed. In HIV+ patients with AIDS or advanced HIV disease (CDC
      groups IV A, IV C1, and IV D) dead cell removal was impaired and apoptotic debris
      accumulated. Long-term cultures of unstimulated PBMC are an interesting model for
      studying the role of macrophages and/or MGC in the removal of dead cells as well
      as examining the cellular milieu in which HIV replicates in an individual host.

PMID- 9000479
TI  - Interleukin-6 overexpression cannot generate serious disorders in severe combined
      immunodeficiency mice.
AB  - C57BL/6 human interleukin-6 (IL-6) transgenic mice develop mesangial
      proliferative glomerulonephritis with massive IgG1 plasmacytosis and die of renal
      failure in early life. To test whether the IL-6 overexpression could cause
      development of mesangial proliferative glomerulonephritis without plasmacytosis
      or promote proliferation of immature B cells that have not undergone
      immunoglobulin gene rearrangement, the IL-6 transgene was introduced into mice
      with severe combined immunodeficiency (SCID). In the immunocompetent littermate
      IL-6 transgenic mice, there were various symptoms such as plasmacytosis,
      nephropathy, anemia, and thrombocytosis, accompanied by marked increases in serum
      IL-6 levels as they aged. All these mice died by 25 weeks of age. In contrast,
      the SCID-IL-6 transgenic mice had no such abnormalities, except certain
      hematological changes, although the transgene was expressed in various tissues.
      In these mice, the serum IL-6 levels were 10- to 15-fold higher than those in the
      nontransgenic mice, and they remained constant throughout their lives.
      Furthermore, there were no signs of lymphoid development. This study demonstrates
      that deregulation of IL-6 expression does not stimulate cell growth or
      differentiation of immature B cells, and thus does not result in plasmacytosis
      and age-related increases in IL-6 production, and also does not generate
      mesangial proliferative glomerulonephritis.

PMID- 9000480
TI  - Phenotypic and functional alterations of thymic nurse cells following acute
      Trypanosoma cruzi infection.
AB  - Acute Trypanosoma cruzi infection induces alterations in both lymphoid and
      microenvironmental compartments of the thymus. This prompted us to investigate
      whether the lymphoepithelial complex thymic nurse cell (TNC) was comprised in the
      thymic pathology occurring in experimental Chagas' disease. The isolation of TNCs
      from acutely T. cruzi-infected mice revealed a reduction in TNC numbers that
      paralleled thymic atrophy. This decrease does not seem to be stress-related since
      it was not seen following glucocorticoid hormone injection. Moreover, an
      increased intra-TNC cell death in complexes from infected animals was noticed. In
      addition, acute T. cruzi infection induced a decrease in size and granularity of
      TNC complexes, as well as several ultrastructural alterations indicating cell
      damage. The epithelial component of TNCs, independent of being infected in vitro
      or derived from infected animals, showed an enhancement of extracellular matrix
      proteins that is likely related to the enhanced thymocyte release observed in
      these complexes. Conjointly, these data show that TNCs are importantly affected
      in acute experimental T. cruzi infection, possibly contributing to the previously
      observed alterations in thymocyte differentiation.

PMID- 9000481
TI  - Membrane tumor necrosis factor-alpha (TNF-alpha) expressed on HTLV-I-infected T
      cells mediates a costimulatory signal for B cell activation--characterization of
      membrane TNF-alpha.
AB  - The 26-kDa membrane tumor necrosis factor-alpha (TNF-alpha) expressed on
      activated CD4(+) T cells is a novel candidate for the functional membrane
      molecule in T-B cell interactions. We found that normal human T cells, when
      infected with human T cell lymphotropic virus type I (HTLV-I) in vitro, were
      induced to express the 26-kDa membrane TNF-alpha. The infected T cells, through
      this molecule, activated autologous B cells to produce immunoglobulin (Ig)M in a
      contact-dependent manner, which was partially inhibited by anti-TNF-alpha
      antibody (Ab). IgG synthesis was not stimulated, however, probably because of
      lack of CD40 ligand expression on the infected T cells. Anti-TNF-alpha Ab
      treatment stimulated the secretion of interleukin (IL)-2 and interferon gamma
      (IFN-gamma) in the infected T cells. These effects were not induced by anti-TNF
      receptor Ab treatment. Anti-TNF-alpha Ab also induced the elevation of
      intracellular calcium concentration in the infected T cells. These results
      suggest that T cells expressing membrane TNF-alpha can be directly stimulated
      through this molecule. Thus, it is suggested that the 26-kDa membrane TNF-alpha
      on HTLV-I-infected T cells plays a role in polyclonal B cell activation and may
      be involved in the pathogenesis of some HTLV-I-associated diseases. Additionally,
      our results suggest a novel mechanism by which cytokine production can be
      modulated in these T cells through membrane TNF-alpha on their surface.

PMID- 9000482
TI  - Preferential binding with Escherichia coli hsp60 of antibodies prevalent in sera
      from patients with rheumatoid arthritis.
AB  - One hundred thirty-two patients with various connective tissue disorders,
      including 60 with rheumatoid arthritis (RA), had antibodies against human as well
      as Escherichia coli hsp60 in titers significantly higher than those of normal
      controls. There was a correlation between titers of antibody to human hsp60 and
      those to E. coli hsp60. Levels of antibodies against human and E. coli hsp60 were
      lower in joint fluids than in sera, indicating little production of antibodies in
      the joint. Antibodies affinity-purified with E. coli hsp60 bound strongly with
      the homologous hsp60, but weakly with human hsp60. However, antibodies affinity
      purified with human hsp60 bound comparably with both E. coli hsp60 and human
      hsp60. Antibodies affinity-purified with Mycobacterium tuberculosis hsp65 bound
      to human hsp60 with a reactivity similar to the reactivity of those affinity
      purified with human hsp60. The reactivity to the three hsp60 species was lost
      when sera were absorbed with E. coli hsp60, while the reactivity to E. coli hsp60
      remained after extensive absorption with M. tuberculosis hsp65 or human hsp60.
      These results indicate that anti-hsp60 antibodies in patients with RA and other
      connective tissue disorders are raised by infection with intestinal
      microorganisms such as E. coli. They may represent another example of autoimmune
      responses triggered by antigenic mimicry of host proteins to microbes and suggest
      that the reactivity of antibodies from RA patients with M. tuberculosis hsp65
      might have been a cross-reaction with the E. coli homologue.

PMID- 9000483
TI  - Altered (oxidized) C1q induces a rheumatoid arthritis-like destructive and
      chronic inflammation in joint structures in arthritis-susceptible rats.
AB  - Previous studies have identified an altered C1q molecule in synovial fluids from
      the joints of rheumatoid arthritis patients. We therefore immunized arthritis
      susceptible Lewis 1A.AVN rats with either native C1q (C1q nat), altered
      (oxidized) C1q (C1q ox), or type II collagen (CII, induces arthritis in these
      animals), in order to induce arthritis. Unlike C1q nat, both CII and C1q ox were
      able to induce swelling and erythema of joints consistent with an arthritis-like
      inflammatory reaction. Histopathological evaluation of individual joint sections
      revealed synovitis, bursitis and tendovaginitis, massive joint destruction, and
      severe pannus formation. In a time-course study, no differences in onset of
      arthritis or pathology were observed between C1q ox-induced arthritis and that
      induced by CII. High titers of antibodies recognizing CII, but not C1q (native or
      oxidized), were detected in rats immunized with CII. In contrast C1q ox, but not
      C1q nat, induced antibodies reactive with both C1q and CII. Antibodies from C1q
      ox-immunized animals contained an antibody subset that reacted with C1q but not
      CII and a subset that reacted with CII but not C1q, implying that induction of an
      immune response to CII does not require CII. These data support the hypothesis
      that C1q may provide one of the early antigens involved in induction of
      arthritis, before CII becomes available as antigen.

PMID- 9000484
TI  - Thyroid peroxidase autoantibodies of IgE class in thyroid autoimmunity.
AB  - Recently, we converted a thyroid peroxidase (TPO)-specific human autoantibody Fab
      (SP1.4) into an IgE molecule (IgE-SP1.4) which permits antigen capture via Fc
      epsilon receptors on B cells and presentation to T cells. An important question
      which arose was whether IgE class TPO autoantibodies are present in vivo. By
      ELISA, TPO autoantibodies of IgG1 and IgG4 subclasses, but not IgE, were readily
      detectable in patients' sera. However, such negative data were not definitive
      because high concentrations of IgG class TPO autoantibodies could obscure the
      presence of much lower concentrations of IgE class autoantibodies. We, therefore,
      established a specific assay based on IgE "capture" to remove other isotypes
      before incubation with TPO. In an initial survey, 125I-TPO binding was higher in
      sera from 16 patients with autoimmune thyroid disease than in 6 controls (8.4 +/-
      0.8% versus 0.7 +/- 0.2%; mean +/- SEM). Unlabeled TPO (10(-8) M) inhibited 125I
      TPO binding by patients' (but not controls') IgE. Further, TPO binding by IgE
      SP1.4 was unaffected by IgG class TPO autoantibodies. Titers of IgE class TPO
      autoantibodies were low, detectable at a 1/60 dilution in 4/5 sera studied. In a
      larger series, IgE class TPO autoantibodies were present in 13 of 18 Graves' and
      in 12 of 17 Hashimoto patients (sera diluted 1/6). Sera were considered to be
      positive with TPO binding greater than the mean + 3 SD of values for 23 control
      sera (1.8%). In conclusion, we provide the first evidence for TPO autoantibodies
      of IgE class in patients with autoimmune thyroid disease. Because of their low
      concentration, these autoantibodies are unlikely to play a role in antigen
      presentation in vivo. However, their presence strengthens the link between
      autoimmune thyroid disease and immune responses involving TH2 cells.

PMID- 9000486
TI  - Analysis of autoantibodies to T-cell receptors among HIV-infected individuals:
      epitope analysis and time course.
AB  - Individuals seropositive for human immunodeficiency virus type 1 (HIV) express
      elevated levels of autoantibodies (AAbs) directed against recombinant T-cell
      receptors (TCRs) and synthetic peptide epitopes duplicating beta chain markers.
      We performed longitudinal studies of anti-TCR AAbs in HIV-1-infected individuals,
      making comparisons with uninfected sera and sera from other individuals infected
      with a nonviral agent. We determined levels of autoantibodies by titration using
      enzyme-linked immunosorbent assay (ELISA) and developed a means for
      characterizing "autoantibody CDR recognition spectrotypes" for individual sera.
      Antibody levels against certain defined synthetic epitopes were substantially
      elevated in HIV-infected subjects relative to reactivities by control groups.
      Individual sera showed relatively high AAb levels to a subset of CDR1 peptide
      epitopes. Two patients who subsequently developed AIDS showed particular
      reactivity to Vbeta2.1, 8.1, 10.1, and 22.1 epitopes. Our results show that
      production AAbs to TCR Vbeta epitopes is a general consequence of HIV infection.
      The response is individual but shows some restriction and shifts in AAb
      subpopulations often occur with time.

PMID- 9000485
TI  - Human immunodeficiency virus (HIV) type-1 GP120-specific cell-mediated
      cytotoxicity (CMC) and natural killer (NK) activity in HIV-infected (HIV+)
      subjects: enhancement with interleukin-2(IL-2), IL-12, and IL-15.
AB  - Cell-mediated cytotoxicity (CMC), as mediated by cytophilic antibody to human
      immunodeficiency virus (HIV) antigens, may be an important defense in HIV
      infected (HIV+) patients in response to the virus. In this study the ability of
      interleukin (IL)-2, IL-12, and IL-15 to enhance natural killer (NK) and gp120
      specific CMC of mononuclear cells (MNCs) from HIV+ children and adults was
      examined. NK activity against K562 cells was deficient in HIV+ patients compared
      to controls and could be enhanced by IL-2, IL-12, or IL-15, with the combinations
      of IL-2 + IL-12 and IL-12 + IL-15 producing more cytotoxicity than individual
      cytokines. Gp120-specific CMC was significantly higher in patients than in
      controls. It could be increased by IL-2, IL-12, and IL-15 and further by
      combining IL-2 and IL-12. When an exogenous source of antibody in the form of
      hyperimmune HIV-specific immunoglobulin (HIVIG) was present, the response of
      control MNCs was much higher than that of patients, although gp120-specific
      cytotoxicity of patients' MNCs was significantly enhanced (two- to threefold) by
      the addition of HIVIG. This increment in cytotoxicity due to HIVIG, however,
      could not be further augmented by cytokines in controls or patients. Our findings
      suggest multiple cytokine administration to boost NK cell function, together with
      passive immunotherapy, might offer a new therapeutic approach to benefit HIV+
      patients.

PMID- 9000487
TI  - Comparison of natural killer (NK) sensitivities of two tumor cell lines
      established from a cancer patient before and after radiation therapy.
AB  - Major histocompatibility complex (MHC) class I positive tumor cells are generally
      resistant to natural killer (NK) cells. In this report, we compared the NK
      sensitivities of tumor cell lines H41 and H42, which were established from a
      cancer patient at surgery. H41 was established before radiation therapy and H42
      was established after the radiation therapy in 1985. H41 was resistant to NK
      cells, whereas H42 was NK-sensitive. Both cell lines reacted with W6/32, which is
      an antibody to the HLA common epitope determinant. However, H42 did not react to
      anti-HLA-locus-specific antibodies, although H41 reacted to them. When these cell
      lines were treated with interferon-gamma, H41 showed an increase in HLA-locus
      specific antigenicity, whereas H42 did not show such a tendency. This suggests
      that there may have been interference in the expression of the HLA-locus-specific
      determinants on H42. Therefore, it was assumed that the NK sensitivity of H42 may
      be due to depression of an HLA-locus-specific determinant, and this depression
      may be related to the radiation therapy. The patient recovered from the disease
      after the radiation therapy and the last surgery. He is now in a tumor-free
      state. We propose that his recovery may be related to the conversion of the tumor
      cells from NK-resistant to NK-sensitive.

PMID- 9000488
TI  - Rate estimation from prevalence information on a simple epidemiologic model for
      health interventions.
AB  - Health intervention control programs, such as vaccination, can be evaluated by
      comparing incidence rates of infection between unprotected and protected
      individuals in a population. The ratio of incidence rates is usually estimated by
      following up control and treated groups in order to collect information on person
      time and cases in each group. This approach can be expensive and time consuming.
      An alternative approach is to use prevalence data to reconstitute incidence.
      Current-status are readily available or easily gathered and can be used to
      estimate incidence rates. Under certain assumptions of irreversibility for the
      outcome of interest, we discuss a simple transmission model appropriate to
      evaluate health interventions that confer long term protection. Rates and
      populations are parameter-free functions of age and calendar time. We develop
      general mathematical relationships that link incidence and intervention rates to
      prevalence which could be estimated from sampling without requiring knowledge of
      subpopulation demographics.

PMID- 9000489
TI  - Estimation in an island model using simulation.
AB  - Estimation for an island model where mutation maintains a k-allele neutral
      polymorphism at a single locus on each island is considered. The likelihood of an
      observed sample type configuration is obtained by applying a computational
      algorithm analogous to Griffiths and Tavare (Theor. Popul. Biol. 46 (1994), 131
      159). This allows the computation of sampling distributions in an island model
      and investigation of their properties. Given a sample type configuration, the
      maximum likelihood estimate of the migration parameter is obtained by simulating
      independently the likelihood at a grid of points and, also, using a surface
      simulation method. The latter method generates the whole likelihood trajectory in
      a single application of the simulation program. An estimate of variance of the
      estimate of the migration parameter is obtained using the likelihood trajectory.
      A comparison of the maximum likelihood estimates of the gene flow between
      subpopulations is made with those obtained by using Wright's FST statistic.

PMID- 9000490
TI  - Establishment probability in fluctuating environments: a branching process model.
AB  - We study the establishment probability of invaders in stochastically fluctuating
      environments and the related issue of extinction probability of small populations
      in such environments, by means of an inhomogeneous branching process model. In
      the model it is assumed that individuals reproduce asexually during discrete
      reproduction periods. Within each period, individuals have (independent) Poisson
      distributed numbers of offspring. The expected numbers of offspring per
      individual are independently identically distributed over the periods. It is
      shown that the establishment probability of an invader varies over the
      reproduction periods according to a stable distribution. We give a method for
      simulating the establishment probabilities and approximations for the expected
      establishment probability. Furthermore, we show that, due to the stochasticity of
      the establishment success over different periods, the expected success of
      sequential invasions is larger then that of simultaneous invasions and we study
      the effects of environmental fluctuations on the extinction probability of small
      populations and metapopulations. The results can easily be generalized to other
      offspring distributions than the Poisson.

PMID- 9000491
TI  - The stability and persistence of mutualisms embedded in community interactions.
AB  - In this paper we argue that two-species models of mutualism may be
      oversimplifications of the real world that lead to erroneous predictions. We
      present a four-species model of a pollination mutualism embedded in other types
      of community interactions. Conclusions derived from two-species models about the
      destabilizing effect of mutualisms are misleading when applied to the present
      scenario; although the mutualisms are locally destabilizing, the effect is more
      than canceled by an increased chance of feasibility. The crucial difference is
      the interaction of the mutualists with other species in a larger web.
      Furthermore, community persistence (without unrealistic population explosion),
      arguably a superior ecological criterion, is greatly enhanced by the presence of
      mutualisms. Therefore, we predict that mutualisms should be common in the real
      world, a prediction matching empirial findings and in contrast to the predictions
      from local stability analysis of basic two-species models. This method of
      stabilizing a mutualism appears superior in some ways to the often-used method of
      introducing density dependence in the strength of the mutualism, because it
      permits obligate mutualisms to exist even at low densities, again matching
      empirical findings. Lastly, this study is an example of how complex model
      assemblages can behave qualitatively differently from analogous simpler ones.

PMID- 9000492
TI  - Dynamics and equilibrium behavior of cytonuclear disequilibria under genetic
      drift, mutation, and migration.
AB  - A simple two-locus drift model for cytonuclear systems is developed, in which the
      stochastic dynamics of cytonuclear genotypic frequencies are specified. Random
      union of zygotes is assumed. Trajectories for the first two moments of both
      genotypic and allelic disequilibria are given under three scenarios: (i) random
      drift alone; (ii) random drift with mutation; and (iii) random drift with
      migration. Steady state solutions for the cytonuclear disequilibria are reported.
      The utility of this simple two-locus drift model in testing the neutrality of
      mitochondrial DNA markers in artificial hybrid zones is briefly illustrated

PMID- 9000493
TI  - Statistics for microsatellite variation based on coalescence.
AB  - The stepwise mutation model, which was at one time chiefly of interest in
      studying the evolution of protein charge-states, has recently undergone a
      resurgence of interest with the new popularity of microsatellites as phylogenetic
      markers. In this paper we describe a method which makes it possible to transfer
      many population genetics results from the standard infinite sites model to the
      stepwise mutation model. We study in detail the properties of pairwise
      differences in microsatellite repeat number between randomly chosen alleles. We
      show that the problem of finding the expected squared distance between two
      individuals and finding the variance of the squared distance can be reduced for a
      wide range of population models to finding the mean and mean square coalescence
      times. In many cases the distributions of coalescence times have already been
      studied for infinite site problems. In this study we show how to calculate these
      quantities for several population models. We also calculate the variance in mean
      squared pairwise distance (an estimator of mutation rate x population size) for
      samples of arbitrary size and show that this variance does not approach zero as
      the sample size increases. We can also use our method to study alleles at linked
      microsatellite loci. We suggest a metric which quantifies the level of
      association between loci-effectively a measure of linkage disequilibrium. It is
      shown that there can be linkage disequilibrium between partially linked loci at
      mutation-drift equilibrium.

PMID- 9000494
TI  - Measures of variation at DNA repeat loci under a general stepwise mutation model.
AB  - Polymorphisms at tandem repeat loci are caused by mutations with allele sizes
      occasionally altered by more than one repeat unit in both forward and backward
      directions. Such mutational changes may occur with asymmetric probabilities.
      Therefore, a one-step symmetric stepwise mutation model may not be appropriate
      for studying the population dynamics at all repeat loci. In this work, we
      evaluated the expectation and variance of the within-population variance of the
      allele size distribution in a finite population, and the expected homozygosity at
      a locus by the coalescence approach under a general stepwise mutation model,
      where mutational transitions of allele sizes can be arbitrary, including being
      asymmetric. Under the special cases of symmetric one-step, two-step, and multi
      step geometric distributions of mutations, our general results reduce to the
      corresponding results obtained by earlier investigators. The general results
      indicate that in a finite population, which has reached a steady state under the
      (general stepwise) mutation and drift balance, the within-population variance of
      allele sizes has a simple expectation (i.e., proportional to Nnu, the product of
      the mutation rate, nu, and effective population size, N). However, its stochastic
      variance is a quadratic function of this composite parameter, Nnu. Furthermore,
      this second-order variance does not decay with the number of alleles sampled from
      a population. Application of this theory to data on allele size distributions in
      unrelated Caucasians from the CEPH pedigree (obtained from the Genome Data Base)
      shows that the relationship of the variance and mean of within-population
      variance of allele sizes at tandem repeat loci, grouped by their chromosomal
      assignment, has a trend compatible with the theory. However, there is an
      indication that the second-order variance is generally underestimated. One reason
      for this departure might be that the CEPH sample may not represent a single
      homogeneous population that reached equilibrium at all tandem repeat loci.

PMID- 9000496
TI  - Past sex prejudice and present sex ratios.

PMID- 9000495
TI  - Lotka's game in predator-prey theory: linking populations to individuals.
AB  - This paper further examines an individual-based model of a spatially distributed
      predator-prey population that demonstrates strong spatial structuring in contrast
      with predictions from its representative analytic formulation. Examination of a
      small, localized population reveals that extinctions due to demographic
      stochasticity dominate the dynamics. Local extinction dynamics produce wave
      pulses and the interactions of these wave pulses constitute global dynamics. The
      results motivate a population-level cell-based model with each cell representing
      a local population and parameterized by local extinction probabilities, rather
      than individual-based interaction rates. A detailed comparison of spatiotemporal
      plots from the two modelling frameworks shows that the population-level model
      captures the broad range of dynamics exhibited by the individual-based model. The
      agreement between these two complementary theoretical frameworks, one formulated
      at the level of individuals, the other at the level of populations, provides a
      mechanistic understanding of the dynamics.

PMID- 9000497
TI  - The immunobiology of Helicobacter pylori gastritis.
AB  - Helicobacter pylori is the major causative agent of chronic gastritis. It is
      associated with duodenal and gastric ulcer and with the majority of primary
      gastric B-cell lymphomas; furthermore, there is a strong epidemiological
      association with gastric cancer. One intriguing aspect of this infection is the
      ability of H pylori to persist despite the vast array of host immune responses.
      This article reviews what is known about the immune responses against H pylori,
      emphasizing what is generally accepted and applicable while highlighting areas of
      controversy. The first section delineates the genesis of the inflammatory
      responses, which initiate with the production of tumor necrosis factor (TNF)
      alpha, interferon (IFN)-gamma, interleukin (IL)-1, IL-6, and IL-8 and continue
      with the recruitment of neutrophilic polymorphonuclear cells, lymphocytes, plasma
      cells, macrophages and eosinophils, and later with the development and
      recruitment of specifically committed cells (lymphocytes sensitized to H pylori
      antigens and B cells producing immunoglobulin (Ig)A, IgG, and possibly IgE
      antibodies against a variety of H pylori surface and flagellar proteins as well
      as bacterial toxins). The second part of the article focuses on the development
      of lymphoid follicles in the gastric mucosa, a phenomenon that for the first time
      links an immune response (the recruitment of mucosa-associated lymphoid tissue
      [MALT] to the gastric mucosa in response to H pylori infection) with the
      development of a neoplastic growth (the development of gastric MALT lymphomas).
      The local and systemic antibody responses are discussed in the light of their
      potential application in the development of diagnostic tests and vaccines.
      Particular emphasis is placed on the controversies surrounding the significance
      of antibodies directed against a 120 to 140 kDa protein apparently associated
      with more "aggressive" (sometimes also called "ulcerogenic" or "pathogenic")
      strains of H pylori.

PMID- 9000498
TI  - Clostridium difficile infection: pathophysiology and diagnosis.
AB  - Clostridium difficile is a relatively common enteric pathogen encountered most
      frequently in association with antibiotic use and as a nosocomial pathogen. Four
      factors dictate clinical expression: (1) acquisition of the organism from
      environmental sources or previous colonization; (2) distortion of the competing
      colonic flora by antibiotics; (3) toxin production; and (4) age-related
      susceptibility. Characteristics of clinical features include inflammatory
      diarrhea (cramps, fecal leukocytes, systemic response), endoscopic evidence of
      colitis or pseudomembranous colitis, and protein-losing enteropathy. The usual
      diagnostic tests are designed to detect toxin B with a tissue culture assay or
      toxin A with an enzyme immunoassay.

PMID- 9000499
TI  - Gastrointestinal manifestations of primary immunodeficiency disorders.
AB  - Because the gastrointestinal tract is the largest lymphoid organ in the body, it
      is not surprising that patients with immunodeficiency would present with
      pathological conditions in the intestine. Several studies have documented a high
      prevalence of inflammatory, malignant, and infectious gastrointestinal (GI)
      disorders in patients with common variable immunodeficiency or immunoglobulin A
      (IgA) deficiency. Interestingly, it has become increasingly apparent that
      antibody deficiency alone does not result in GI disease. Rather, defects in
      cellular immunity appear to predispose to a sprue-like disorder, pernicious
      anemia, giardiasis, nodular lymphoid hyperplasia, and even inflammatory bowel
      disease. In patients with unusual inflammatory GI disorders, measurement of serum
      immunoglobulins should be obtained.

PMID- 9000500
TI  - Gut Coccidia--Isospora, Cryptosporidium, Cyclospora and Sarcocystis.
AB  - The gut Coccidia are members of a large, varied, and exclusively intracellular
      group of protozoan parasites, four species of which (Isospora, Cryptosporidium,
      Cyclospora, and Sarcocystis) are human pathogens. The first three, but
      particularly Cryptosporidium parvum, have moved from medical curiosities to major
      problems with the coming of the acquired immunodeficiency syndrome (AIDS)
      epidemic, but are now known to also cause disease in the immunocompetent patient.
      They are easy to acquire and difficult to remove from the environment and, in the
      case of cryptosporidiosis, impossible to treat properly. Further research into
      many aspects of the biology of these organisms is urgently needed.

PMID- 9000501
TI  - Intestinal microsporidiosis.
AB  - Intestinal microsporidiosis is caused by the protozoan parasites Enterocytozoon
      bieneusi and Encephalitozoon intestinalis. The disease has been described within
      the past decade and is found predominantly in acquired immunodeficiency syndrome
      (AIDS) patients in association with diarrhea. There have been rare reports of
      infections in immunocompetent patients. Both species of microsporidia invade and
      multiply within the enterocytes of the small intestine; Encephalitozoon
      intestinalis also causes a disseminated infection. Electron microscopy has been
      the mainstay of diagnosis, but improved noninvasive methods of detecting spores
      in feces are in development. The biology and pathogenicity of the parasites and
      the pathology and treatment of the disease are poorly understood.

PMID- 9000502
TI  - Vertebrate evolution by interspecific hybridisation--are we polyploid?
AB  - For the growing fraction of human genes with identified functions there are often
      homologues known from invertebrates such as Drosophila. A survey of well
      established gene families from aldolases to zinc finger transcription factors
      reveals that usually a single invertebrate gene corresponds to up to four equally
      related vertebrate genes on different chromosomes. This pattern was before widely
      noticed for the Hox gene clusters but appears to be more general. Genome
      quadruplication by two rounds of hybridisation is discussed as a simple
      biological mechanism that could have provided the necessary raw material for the
      success of vertebrate evolution.

PMID- 9000503
TI  - c-Fos transrepression revisited.
AB  - The c-fos proto-oncogene was discovered by homology to transforming viral genes,
      leading to speculation that transforming viruses had captured a cellular gene
      involved in cell cycle control. Indeed overexpression of c-Fos protein led to
      deregulated growth control, and c-Fos was thought to be so critically involved in
      cell cycle control that transcriptional transrepression of its own promoter was
      interpreted as a negative feedback mechanism. However, recent findings render
      this conclusion improbable, Fos transrepression being most parsimoniously
      explained as transcriptional squelching imposed by artificially elevated levels
      of exogenous Fos protein.

PMID- 9000504
TI  - Tyrosine phosphorylation and Fcgamma receptor-mediated phagocytosis.
AB  - Phagocytosis of IgG-opsonized particulate material in hematopoietic cells is
      mediated by Fcgamma receptors (FcgammaRs). Interaction of the receptors with Fc
      domains of IgG triggers transduction of phagocytic signal in which a key role is
      played by phosphorylation of tyrosine residues of the receptors. These residues
      are arranged into a specific motif (immunoreceptor tyrosine-based activation
      motif; ITAM) which is located either in the cytoplasmic part of FcgammaRIIA or in
      gamma chains associated with FcgammaRI and FcgammaRIIIA. The conserved tyrosine
      residues are phosphorylated by, and associate with, tyrosine kinases of Src and
      Syk families. Coordinated action of these components initiates numerous
      intracellular events leading finally to local rearrangement of the actin-based
      cytoskeleton and internalization of the particles.

PMID- 9000505
TI  - Ceramides induce a form of apoptosis in human acute lymphoblastic leukemia cells
      that is inhibited by Bcl-2, but not by CrmA.
AB  - The generation of ceramides by the action of acidic and/or neutral
      sphingomyelinases has been implicated in many forms of apoptosis. We investigated
      whether exposure to ceramides is sufficient to induce apoptosis in human leukemia
      cells and, if so, what the characteristics of this form of apoptosis might be.
      Treatment of the acute lymphoblastic T-cell line CEM-C7H2 with short- and medium
      chain ceramide analogs (C2-, C6-, and C8-ceramide) resulted in apoptosis, whereas
      the inactive C2-dihydroceramide had no effect on cell survival. Induction of
      apoptosis was relatively slow (approximately 40% after 24 h) and required high
      concentrations of ceramide analogs (40-100 microM). To investigate a possible
      involvement of interleukin 1-beta-converting enzyme (ICE) or ICE-related
      proteases, we treated CEM-C7H2 sublines constitutively expressing the vaccinia
      virus protease inhibitor crmA with ceramide analogs. Although such cells were
      completely resistant to apoptosis induced by antibodies to the Apo-1/Fas surface
      receptor (a form of apoptosis known to be inhibitable by CrmA), they were not
      protected from ceramide-induced cell death. In contrast, tetracycline-regulated
      overexpression of Bcl-2 protected CEM-C7H2 sublines stably transfected with
      corresponding constructs from ceramide-induced apoptosis. Thus, in these human
      leukemia cells, ceramides induce a relatively slow death response that can be
      prevented by Bcl-2, but is independent of CrmA-inhibitable proteases. These
      characteristics distinguish ceramide-induced from other forms of apoptosis, such
      as Apo-1/Fas-induced cell death where ceramide production has been causally
      implicated.

PMID- 9000506
TI  - Characterisation of S-nitrosohaemoglobin by mass spectrometry.
AB  - Recent studies have demonstrated the biological importance of the interaction of
      S-nitrosothiols, which can be considered as nitric oxide (NO) protein donors,
      especially haemoglobin, at the level of Cys residues. It was recently proposed
      that S-nitrosohaemoglobin is formed within red blood cells and serves as a
      regulatory function. In human haemoglobin the alpha-subunit contains one Cys
      residue and the beta-subunit contains two Cys residues, one of which (beta-Cys93)
      is highly reactive and conserved among species, although its function has
      remained unknown. Electrospray ionization mass spectrometry was used to monitor
      the results of exposure of haemolysates to S-nitrosocysteine under different
      conditions and thus addressed some aspects of NO-haemoglobin interaction. When an
      equimolar ratio of S-nitrosothiol was added to haemoglobin, only a single NO
      molecule was added. Peptide mapping by liquid chromatography-mass spectrometry
      located the nitrosyl group at the level of beta-Cys93 demonstrating that this was
      the preferred site of formation of S-nitrosohaemoglobin. The present data also
      suggest that electrospray mass spectrometry can allow quantification and
      characterisation of S-nitrosoproteins in blood.

PMID- 9000507
TI  - From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair.
AB  - Inherited mutations in BRCA1 predispose to breast and ovarian cancer, but the
      biological function of the BRCA1 protein has remained largely elusive. The recent
      correspondence of Koonin et al. [Koonin, E.V., Altschul, S.F. and Bork, P. (1996)
      Nature Genet. 13, 266-267] has emphasized the potential importance of the BRCA1 C
      terminal region for BRCA1-mediated breast cancer suppression, as this domain
      shows similarities with the C-terminal regions of a p53-binding protein (53BP1),
      the yeast RAD9 protein involved in DNA repair, and two uncharacterized,
      hypothetical proteins (KIAA0170 and SPAC19G10.7). The highlighted domain has been
      suggested to be the result of an internal duplication, each of the tandem domains
      being designated as a 'BRCT domain' (for BRCA1 C-terminus). Sequence analysis
      using hydrophobic cluster analysis reveals here the presence of 50 copies of the
      BRCT domain in 23 different proteins, including, in addition to BRCA1, 53BP1 and
      RAD9, XRCC1, RAD4, Ect2, REV1, Crb2, RAP1, terminal deoxynucleotidyltransferases
      (TdT) and three eukaryotic DNA ligases. Most of these proteins are known to be
      involved in DNA repair. The BRCT domain is not limited to the C-termini of
      protein sequences and can be found in multiple copies or in a single copy as in
      RAP1 and TdT, suggesting that it could well constitute an autonomous folding unit
      of approx. 90-100 amino acids.

PMID- 9000508
TI  - The role of the proline-rich region in A1-type myosin essential light chains:
      implications for information transmission in the actomyosin complex.
AB  - The proline-rich region of A1-type myosin essential light chains functions as a
      spacer arm separating an actin binding site at the extreme N-terminus from the
      remainder of the protein. Alteration of the length of this region leaving the
      actin binding site intact results in altered actin-activated MgATPase kinetics
      when these light chains are hybridised into myosin subfragment-1. In the case of
      a mutant in which the length of the proline-rich region was doubled, actin
      binding by the light chain was uncoupled from kinetic modulation. The
      implications of this result for information transmission in the actomyosin
      complex are discussed.

PMID- 9000509
TI  - In vitro low propensity to form nucleosomes of four telomeric sequences.
AB  - The structural aspects of nucleosome assembly on telomeres are largely unknown.
      We analyzed by competitive reconstitution the affinities for the histone octamer
      of telomeric sequences from four different eukaryotic groups, Arabidopsis
      thaliana, mammals, Tetrahymena, and Saccharomyces cerevisiae. All telomeres
      reconstitute in nucleosomes with lower association constants than average
      nucleosomal DNA. DNase I digestion analysis suggests a multiple translational
      positioning and the lack of rotational positioning, probably due to telomeric
      repeats length (in most cases 6-8 bp), out of phase with the DNA helical repeat
      on the nucleosome (10.2 bp). These results could partly explain the lack of
      nucleosomes on lower eukaryote telomeres, and suggest a high in vivo mobility of
      telomeric nucleosomes.

PMID- 9000510
TI  - Substrate activation behaviour of pyruvate decarboxylase from Pisum sativum cv.
      Miko.
AB  - The substrate activation behaviour of pyruvate decarboxylase from germinating
      seeds of Pisum sativum is characterised kinetically via stopped-flow measurements
      and discussed with respect to other species. The involvement of SH-groups in this
      process is demonstrated by reference experiments with chemically modified enzyme.

PMID- 9000511
TI  - Casein kinase II phosphorylates Ser468 in the PEST domain of the Drosophila
      IkappaB homologue cactus.
AB  - Cactus protein is a Drosophila homologue of the mammalian IkappaB family of
      cytoplasmic anchor proteins. In unstimulated cells they function to retain
      rel/NFkappaB transcription factors in the cytoplasm but are rapidly degraded in
      response to signalling. The destruction of cactus or IkappaBalpha allows the
      rel/NFkappaB transcription factor to relocalise to the nucleus. Cactus is a
      phosphoprotein and has in its C-terminus a PEST protein stability domain. In this
      paper we show that, like mammalian IkappaBalpha, the PEST domain of cactus is
      phosphorylated by casein kinase II. We have localised the site of modification to
      a single residue, Ser468, and find no evidence for additional phosphorylation
      sites. The conservation of these sites in mammalian and invertebrate cytoplasmic
      anchor proteins suggests that phosphorylation by casein kinase II may play a
      critical functional role, plausibly in the regulation of constitutive or
      inducible proteolysis.

PMID- 9000512
TI  - Aluminum interaction with plasma membrane lipids and enzyme metal binding sites
      and its potential role in Al cytotoxicity.
AB  - The trivalent cation aluminum can cause chronic cytotoxicity in plants, animals
      and microorganisms. It has been suggested that Al interaction with cell membranes
      and enzyme metal binding sites may be involved in Al cytotoxicity. In this study,
      the binding of Al to microsomes and liposomes was found to be lipid dependent
      with the signal transduction element phosphatidylinositol-4,5-bisphosphate having
      the highest affinity for Al with an Al:lipid stoichiometry of 1:1. Al binding was
      only reduced in the presence of high concentrations of Ca2+ (> 1 mM). Both
      citrate and, to a lesser extent, malate were capable of preventing Al lipid
      binding, which is consistent with the involvement of these organic acids in a
      recently described Al detoxification mechanism in plants. The effects of AICl3,
      Al-citrate and ZnSO4 on metal-dependent enzyme activities (enolase, pyruvate
      kinase, H+-ATPase, myosin, Calpain, proteinase K, phospholipase A2 and arginase)
      was assayed in vitro. While Zn2+ was capable of inhibiting all the enzymes except
      the H+-ATPase, AlCl3 and Al-citrate had minimal effects except for with
      phospholipase A2 where an interaction with AlCl3 occurred. However, this could be
      negated by the addition of citrate. The results indicate that, contrary to
      current hypotheses, the toxic mode of Al is not through an interaction with
      enzymatic catalytic metal binding sites but may be through the interaction with
      specific membrane lipids.

PMID- 9000513
TI  - Propagation of intercellular Ca2+ waves in mechanically stimulated articular
      chondrocytes.
AB  - Intercellular Ca2+ signalling in primary cultures of articular chondrocytes was
      investigated with digital fluorescence video imaging. Mechanical stimulation of a
      single cell induced a wave of increased Ca2+ that was communicated to surrounding
      cells. Intercellular Ca2+ spreading was inhibited by 18alpha-glycyrrhetinic acid,
      demonstrating the involvement of gap junctions in signal propagation. In the
      absence of extracellular Ca2+ mechanical stimulation failed to induce Ca2+
      responses and communicated Ca2+ waves. Under these conditions Ca2+ microinjection
      induced intercellular waves involving the cells immediately surrounding the
      stimulated one. Mechanical stress induced Ca2+ influx in the stimulated, but not
      in the adjacent cells, as assessed by the Mn2+ quenching technique. Cell
      treatment with thapsigargin failed to block mechanically induced signal
      propagation, but significantly reduced the number of cells involved in the
      communicated Ca2+ wave. Similar results were obtained with the phospholipase C
      inhibitor U73122, which is known to prevent InsP3 generation. These results
      provide evidence that mechanical stimulation induces a cytosolic Ca2+ increase
      that may permeate gap junctions, thus acting as an intercellular messenger
      mediating cell-to-cell communication in articular chondrocytes.

PMID- 9000514
TI  - Identification of Ser-1275 and Ser-1309 as autophosphorylation sites of the
      insulin receptor.
AB  - We have identified Ser-1275 and Ser-1309 as novel serine autophosphorylation
      sites by direct sequencing of HPLC-purified tryptic phosphopeptides of the
      histidine-tagged insulin receptor kinase IRKD-HIS. The corresponding peptides
      (Ser-1275, amino acids 1272-1292; Ser-1309, amino acids 1305-1313) have been
      detected in the HPLC profiles of both the soluble kinase IRKD, which contains the
      entire cytoplasmic domain of the insulin receptor beta-subunit, and the insulin
      receptor purified from human placenta. In contrast, a kinase negative mutant,
      IRKD-K1018A, did not undergo phosphorylation at either the tyrosine or serine
      residues, strongly suggesting that insulin receptor kinase has an intrinsic
      activity to autophosphorylate serine residues.

PMID- 9000515
TI  - Distinct roles of mouse laminin beta1 long arm domains for alpha1beta1gamma1
      trimer formation.
AB  - Mouse embryonal carcinoma F9 cells expressing partial mouse laminin beta1
      covering either the C-terminal end (delta beta1S) or the whole (delta beta1L) of
      the long arm were established to study the assembly and interchain disulfide
      bonding of beta1 to endogenous laminin alpha1 and gamma1. Both delta beta1S and
      delta beta1L were disulfide-bonded to gamma1 but only delta beta1L gamma1 dimer
      formed a disulfide-bonded alpha1 delta beta1L gamma1 trimer which was actively
      secreted into the medium. Meanwhile, in the cells producing delta beta1S gamma1
      dimer, the level of endogenous alpha1 beta1 gamma1 was reduced but the level of
      monomeric alpha1 was increased, suggesting that alpha1 was recruited to trimer
      formation with the delta beta1S gamma1 dimer without disulfide-bonding. This
      shows that the delta beta1S gamma1 dimer can associate with alpha1 but not
      support the disulfide-bonding at the N-terminus of the long arm of alpha1. While
      control cells secrete neither monomeric alpha1 nor the beta1gamma1 dimer into the
      medium, the delta beta1S gamma1 producing cells probably do as alpha1 delta beta1
      gamma1 trimer. We thus propose that the N- and C-termini of the long arm of
      laminin beta1 have distinct roles for trimer formation.

PMID- 9000516
TI  - Inhibition of nucleoside diphosphate kinase (NDPK/nm23) by cAMP analogues.
AB  - Nucleoside diphosphate kinase (NDPK/nm23) ATP/GDP phosphotransferase activity and
      serine autophosphorylation is inhibited by N6-mbcAMP, 8-ClcAMP and 8-BrcAMP.
      Inhibition of the enzymatic activity largely depends on the concentration of ATP
      and becomes significant at ATP concentrations up to 0.5 mM and at effector
      concentrations measured in C6 cells stimulated with 1 mM cAMP analogue. N6-mbcAMP
      is a substrate of the enzyme. DbcAMP and 0'2-mbcAMP, cAMP analogues with a
      modified 0'2-ribose, did not affect the NDPK activity. Cyclic AMP is only a
      moderate inhibitor of NDPK even at low ATP concentrations. Possible inhibitory
      effects of cAMP and cAMP analogues on reported extra- and intracellular functions
      of NDPK/nm23 are discussed.

PMID- 9000517
TI  - Resistance to fluconazole and cross-resistance to amphotericin B in Candida
      albicans from AIDS patients caused by defective sterol delta5,6-desaturation.
AB  - Fluconazole resistance occurs in > 10% of cases of candidosis during the late
      stages of AIDS. We show here in two clinical isolates that resistance was caused
      by defective sterol delta5,6-desaturation. This altered the type of sterol
      accumulating under fluconazole treatment from 14alpha-methylergosta-8,24(28)-dien
      3beta,6alpha -diol to 14alpha-methylfecosterol which is capable of supporting
      growth. A consequence of this mechanism of azole resistance is that an absence of
      ergosterol causes cross-resistance to the other major antifungal agent available,
      amphotericin B. The results also show that growth arrest after fluconazole
      treatment of C. albicans in clinical conditions is caused by 14alpha
      methylergosta-8,24(28)-dien-3beta,6alpha -diol accumulation.

PMID- 9000518
TI  - Subunit topology of the Rhodococcus proteasome.
AB  - The 20S proteasome, isolated from the nocardioform actinomycete Rhodococcus
      erythropolis strain NI86/21, is built from two alpha-type and two beta-type
      subunits. In order to probe the subunit topology, we have set up an expression
      system which allows coexpression of the genes encoding the alpha- and beta
      subunits in all possible combinations. The four respective constructs obtained
      yielded fully assembled and proteolytically active proteasomes. Biochemical,
      kinetic and electron microscopy analysis allow us to rule out several of the
      models which were originally envisaged for the subunit topology of the
      Rhodococcus proteasome. The experiments further indicate that the assembly
      pathways of the Rhodococcus and of the Thermoplasma proteasome differ in some
      important details.

PMID- 9000519
TI  - Crystallization and preliminary X-ray diffraction analysis of proline
      iminopeptidase from Xanthomonas campestris pv. citri.
AB  - Proline iminopeptidase from Xanthomonas campestris pv. citri, displaying no
      significant sequence homology to any protein previously analyzed by X-ray
      crystallography, has been crystallized using the vapour diffusion method. Two
      different orthorhombic crystal forms (space group C222 and I222) were obtained
      from a solution containing NaCl or polyethylene glycol monomethyl ether (MW 5000)
      as precipitating agent for the native and lanthanum-derivatized protein,
      respectively. Complete diffraction data sets have been collected up to 2.6 A
      (native) and 3.0 A (lanthanum derivative) resolution. Cell dimensions are a=
      147.2 A, b = 167.8 A, and c = 85.6 A (C222) and a = 146.7 A, b = 167.7 A, and c =
      171.4 A (I222), respectively. Considerations of the possible values of V(m) and
      analysis of the self-rotation function of the native crystals account for the
      presence of one dimer per asymmetric unit, whereas a tetramer probably would
      occupy the smallest crystallographically independent crystal portion in the
      lanthanum-derivatized protein crystals.

PMID- 9000520
TI  - Evolution of dnaQ, the gene encoding the editing 3' to 5' exonuclease subunit of
      DNA polymerase III holoenzyme in Gram-negative bacteria.
AB  - The nucleotide sequences of the dnaQ genes from Salmonella typhimurium and
      Buchnera aphidicola, encoding the epsilon-subunit of the DNA polymerase III
      holoenzyme, have been determined. The Salmonella typhimurium dnaQ protein
      consists of 243 amino acid residues with a calculated molecular weight of 27224.
      The Buchnera aphidicola dnaQ protein contains 233 amino acid residues with a
      calculated molecular weight of 27170. A multiple sequence alignment of the amino
      acid sequences of the dnaQ proteins and those of DNA polymerase IIIs from Gram
      positive bacteria produced six homologous segments. These homologous segments
      contain highly conserved amino acid sequence motifs involved in catalytically
      important metal ion bindings (ligands 1, 2 and 3). However, metal ligand 4 is
      found to be altered in the 3'-5' exonuclease domain of the family C DNA
      polymerases and dnaQ proteins in Gram-negative bacteria. From these results, we
      propose that the last common ancestor of the dnaQ gene of Gram-negative bacteria
      and the DNA polymerase III gene (pol C gene) of Gram-positive bacteria was a
      single gene containing both 3'-5' exonuclease and DNA polymerase domains and then
      the dnaQ gene separated from the polymerase gene in Gram-negative bacteria.

PMID- 9000521
TI  - Diacylglycerol mediates the thrombin-induced, protein kinase C and Ca2+
      independent activation of the Na+/H+ exchanger in platelets.
AB  - Treatment of aspirinated platelets with the electroneutral K+/H+ exchanger
      nigericin induces a decrease in intraplatelet pH as measured with the
      intracellular fluorescent indicator BCECF. Under these conditions, the proton
      permeability of the plasma membrane is unaffected. The addition of thrombin
      induces a rapid partial recovery of pH(i), which is completely abolished by the
      Na+/H+ exchanger inhibitor NHA. The effect is also evident in the presence of the
      PKC inhibitors GF 109203X or staurosporine and in the absence of both external
      (EGTA-chelated) and internal (BAPTA-chelated) Ca2+. This makes the thrombin
      induced activation of the exchanger independent of the involvement of the
      hitherto described activators, namely PKC and the increase in [Ca2+]i, as well of
      the recently reported activator arachidonic acid [Cavallini, L., Coassin, M.,
      Borean, A., and Alexandre, A. (1996) Biochem. J. 319, 567-574], whose production
      requires a high [Ca2+]i. The thrombin-dependent recovery of pH(i) is prevented by
      the phospholipase C inhibitor ET 18 O-CH3 and is mimicked by the addition of the
      permeable diglyceride dioctanoyl glycerol (DiC8) exogenously supplied. The effect
      of thrombin and DiC8 is unaffected by inhibition of diacylglycerol lipase and
      diacylglycerol kinase. These experiments identify diglyceride as a novel
      activator of the Na+/H+ exchanger in platelets.

PMID- 9000522
TI  - Primary structure and allergenic activity of trypsin inhibitors from the seeds of
      buckwheat (Fagopyrum esculentum Moench).
AB  - The complete amino acid sequences of two trypsin inhibitors BWI-2a and BWI-2b
      from the seeds of buckwheat (Fagopyrum esculentum Moench) were determined. BWI-2b
      consists of 51 amino acid residues containing two disulfide bonds. BWI-2a shares
      all amino acids with BWI-2b except for the C-terminal tripeptide: BWI-2a lacks
      Glu-Gly-Asn and ends with the Asp residue, making a total of 48 residues in the
      chain. The two disulfide bonds connect Cys11 to Cys32 and Cys15 to Cys28. BWI-2b
      shows no relatedness to the other buckwheat trypsin inhibitor reported
      [Belozersky et al. (1995) FEBS Lett. 371, 264-266]. Sequence comparison of BWI-2b
      with those of the other proteins included in PIR showed that BWI-2b is
      significantly homologous to the N-terminal region of storage proteins classified
      in the vicilin family. Furthermore, the allergenic activity of BWI-2b and the
      other buckwheat trypsin inhibitor BWI-1 was examined using the
      radioallergosorbent test. The result indicated that both inhibitors BWI-2b and
      BWI-1 have IgE binding activity, albeit to a low extent, suggesting that they
      might be minor allergenic proteins in buckwheat seeds.

PMID- 9000524
TI  - Regulation of intracellular chloride concentration in rat lactotrophs: possible
      role of mitochondria.
AB  - Increasing evidence is accumulating for the involvement of chloride ions in the
      stimulus-secretion coupling of pituitary cells. We show that the mean
      intracellular chloride concentration [Cl-]i of rat lactotroph cells maintained in
      culture is high, close to 60 mM (59.4 mM), using the Cl- sensitive fluorescent
      probe 6-methoxy-N-(3-sulfopropyl) quinolinium (SPQ), coupled with whole-cell
      patch-clamp recordings. We demonstrate that this high level is correlated with
      the presence of mitochondrial stores of Cl- as shown by the release of Cl- in
      response to various metabolic inhibitors. We determine that CCP (50 microM)
      induces a mean [Cl-]i increase of 15.8+/-5.8 mM, using combined electrophysiology
      and microspectrofluorimetry methods. These data strongly suggest that cell
      metabolism, including the mitochondrial function, modulate [Cl-]i.

PMID- 9000523
TI  - Instability of expressed Cu/Zn superoxide dismutase with 2 bp deletion found in
      familial amyotrophic lateral sclerosis.
AB  - The mutant Cu/Zn superoxide dismutase (SOD1) associated with familial amyotrophic
      lateral sclerosis (FALS) with a 2 bp deletion was produced in two protein
      expression systems. The mutant SOD1, expressed as a fusion protein in E. coli,
      had immunoreactivity to an anti-human SOD1 antibody but no SOD activity. It was
      more susceptible to proteolysis and its immunoreactivity decreased more rapidly
      than the wild type. The mutant SOD1, expressed in Cos1 cells, was not detected by
      either SOD activity staining or Western blot analysis, although expression of its
      mRNA was confirmed. These results suggest that the mutant SOD1 is seriously
      unstable in mammalian cells.

PMID- 9000526
TI  - Isolation and characterization of new C-terminal substitution mutations affecting
      secretion of polygalacturonase in Erwinia carotovora ssp. carotovora.
AB  - An intact C-terminus was previously shown to be required for stability and
      secretion of the polygalacturonase (PehA) in Erwinia carotovora ssp. carotovora.
      Here we have analyzed the effects of amino acid (aa) substitutions generated to
      five C-terminal positions of PehA. Conservation of two hydrophobic and one non
      hydrophobic residue (V372, V374 and N371, respectively) was found to be essential
      for maintenance of the protein stability. As an exception, one of the mutants
      (V372G) did not show major effects on protein stability, as determined by
      immunoblots and enzyme activity assay, yet it prevented the secretion completely.
      We conclude that the C-terminus of PehA is directly involved in the formation or
      stabilization of a conformation-sensitive structure needed for recognition of the
      protein as secreted.

PMID- 9000525
TI  - Troglitazone inhibits angiotensin II-induced DNA synthesis and migration in
      vascular smooth muscle cells.
AB  - Angiotensin II (AII) plays a crucial role in controlling the proliferation and
      migration of vascular smooth muscle cells (VSMCs). The present study was
      undertaken to determine if troglitazone (Tro) has an effect on the G-protein
      coupled signaling through AII type I (AT-1) receptors in cultured rat aortic
      VSMCs. AII-induced MAP kinase activation was inhibited 67.9% by Tro. AII-induced
      DNA synthesis and migration was completely inhibited by Tro or by the AT-1
      receptor blocker irbesartan. The present study demonstrates that troglitazone
      inhibits AII-induced DNA synthesis, migration and MAP kinase activation in VSMCs
      which are important molecular events for the development of neointimal
      hyperplasia and atherosclerosis.

PMID- 9000527
TI  - G2 cell cycle arrest and apoptosis are induced in Burkitt's lymphoma cells by the
      anticancer agent oracin.
AB  - The cytotoxic effect of the new potential intercalating anticancer drug oracin
      was studied on Burkitt's lymphoma cell line that overexpressed bcl-2 (BL bcl-2)
      and a control transfectant without the bcl-2 gene (BL SV2). Oracin showed a
      marked cytostatic effect on both BL SV2 and BL bcl-2 cells. IC50, as measured by
      the MTT assay, was approx. 5-times greater for BL bcl-2 cells (5.0 micromol/l)
      than for BL SV2 cells (1.0 micromol/l). There was no significant increase in
      apoptosis after 24 h of treatment with oracin (1.0 micromol/l) in both cell
      lines. However, after 48 h from the removal of oracin in BL SV2 culture the
      levels of apoptotic and secondary necrotic cells increased to 20 and 37%,
      respectively. In contrast, BL bcl-2 cells treated in a similar manner showed only
      basal levels of apoptotic and secondary necrotic cells. Analysis of the cell
      cycle profiles showed a significant increase of S and G2/M phases of the cell
      cycle in both cell lines after 6 h of drug treatment (1.0 micromol/l). The cells
      were arrested in G2/M phase of the cell cycle after 24 h, with no significant
      changes in cell viability. After 72 h, the viable BL SV2 cells were still in
      G2/M, however, the viability of this culture had fallen to approx. 5%. Flow
      cytometry analysis of the DNA content revealed the presence of a 'sub-G2' region,
      which represented the apoptotic cells. The BL SV2 cells died after 72 h while
      they were in the G2/M phase. Although the treated BL bcl-2 cells were similarly
      arrested in the G2/M phase, they nevertheless remained with a relatively high
      viability (68%).

PMID- 9000529
TI  - Activation of protein phosphatase 5 by limited proteolysis or the binding of
      polyunsaturated fatty acids to the TPR domain.
AB  - Protein phosphatase 5 (PP5) exhibits very low phosphatase activity, which can be
      stimulated > 25-fold by proteolysis. Since proteolysis cleaves the N-terminal
      tetratricopeptide repeat (TPR) domain from the catalytic domain, these results
      indicate that the TPR domain shields the active site. Polyunsaturated fatty
      acids, such as arachidonic acid, and lipids containing polyunsaturated fatty
      acids, such as phosphatidylinositol, stimulate both bacterially expressed human
      and native rabbit PP5 activity > 25-fold towards casein and myelin basic protein.
      Phosphatidylinositol binds to the TPR domain, and not to the catalytic domain,
      indicating that activation by polyunsaturated fatty acids is allosteric and that
      it may occur by movement of the TPR domain to allow substrate access.

PMID- 9000528
TI  - Brain-to-blood active transport of beta-alanine across the blood-brain barrier.
AB  - A high-affinity antiluminal uptake system for beta-alanine was demonstrated in
      primary cultured bovine brain capillary endothelial cells (BCEC) for which K(t)
      is 66.9 microM. beta alanine uptake was energy-, sodium- and chloride ion
      dependent. beta-amino acids strongly inhibited the uptake, while alpha- and gamma
      amino acids had a little or no inhibitory effect. In ATP-depleted cells, the
      uptake was stimulated by preloading beta-alanine or taurine but not by L-leucine.
      These results suggest that beta-alanine is actively transported across the
      antiluminal membrane of BCECs that is common to beta-amino acids. The system may
      function for the efflux from the brain to blood.

PMID- 9000530
TI  - European workshop on the cell biology of phagocytes.

PMID- 9000532
TI  - Alteration of dealcylated lipopolysaccharide antagonistic properties by
      interaction with plasma factors.
AB  - The acyl poly(1,3)galactoside (APG) from Klebsiella pneumoniae is a bis-acylated
      lipopolysaccharide (LPS) devoid of ester-linked fatty acids. APG interacts with
      CD14 and CD11b/CD18 on monocytes. This study addressed the role of serum proteins
      in the binding and functional properties of APG as a candidate LPS antagonist. In
      the absence of serum, APG did not induce tumor necrosis factor alpha (TNF-alpha)
      synthesis by human mononuclear cells and dose-dependently inhibited their
      activation induced by different LPS. Conversely, in the presence of 5% autologous
      plasma, APG activated cells and did not antagonize LPS. Serum decreased APG but
      not LPS binding to monocytes. Binding competition experiments indicated that APG
      and LPS competed for the same receptors in serum-free conditions but bound to
      different receptors in the presence of plasma. The data indicate that serum
      dependent LPS receptors do contribute to LPS activation of monocytes but do not
      recognize deacylated LPS analogues.

PMID- 9000531
TI  - Immunoreceptor tyrosine-based activation motif (ITAM), a unique module linking
      antigen and Fc receptors to their signaling cascades.
AB  - Signal transduction by the T cell and B cell antigen receptors and by receptors
      for a variety of immunoglobulins' Fc region is strictly dependent on a receptor
      subunit cytoplasmic module termed immunoreceptor tyrosine-based activation motif
      (ITAM). This module exists in one or more copies in each of the receptor
      associated signal-transducing molecules and it possesses two repeats of the
      consensus sequence Tyr-X-X-Leu/Ile spaced by six to eight amino acids. Receptor
      engagement is followed by a rapid and transient phosphorylation of tyrosine
      residues within their ITAMs, thereby creating temporary binding sites for Src
      homology 2 (SH2)-containing signaling molecules operating downstream of the
      activated receptor. The purpose of this review is to discuss recent findings on
      the functional role of ITAMs in antigen and Fc receptor-mediated signal
      transduction, with a particular emphasis on kinases operating upstream and
      downstream of the ITAMs.

PMID- 9000533
TI  - Elevated levels of NO in both unchallenged and LPS-challenged C. parvum-primed
      mice are attributable to the activity of a cytokine-inducible isoform of iNOS.
AB  - Elevated levels of nitric oxide (NO2-/NO3-) were detected in the serum of mice 3
      7 days after priming with Corynebacterium parvum (Propionibacterium acnes). The
      serum NO2-/NO3- response was completely inhibited when C. parvum-primed (C.
      parrum) mice were treated with N(G)-monomethyl-L-arginine (L-NMMA) or
      aminoguanidine (AG) on days 6 and 7 post priming. The response was also inhibited
      when the mice were treated with interleukin-10 (IL-10) and the cytokine was most
      effective when given in multiple doses beginning on the day of priming. In
      contrast to L-NMMA and AG, IL-10 had no effect on the serum NO2-/NO3- response
      when administered to the mice on days 6 and 7 post priming. The inducible isoform
      of NOS (iNOS) appeared to be responsible for the elevated NO2-/NO3- response in
      C. parvum mice because iNOS transcripts were readily detected in their livers.
      Moreover, these transcripts as well as the circulating levels of NO2-/NO3- were
      dramatically reduced when the mice were treated with anti-tumor necrosis factor
      alpha (anti-TNF-alpha) or anti-interferon-gamma (anti-IFN-gamma) monoclonal
      antibodies (mAbs) during the priming interval. There was a modest increase (less
      than twofold) in the serum NO2-/NO3- response following a lipopolysaccharide
      (LPS) challenge to C. parvum mice (C. parvum/LPS mice). LPS had a more dramatic
      stimulatory effect if the levels of NO2-/NO3- preexisting in C. parvum/LPS mice
      were reduced by treatment with L-NMMA, AG, or IL-10 before the challenge. Thus
      the levels of NO2-/NO3- that preexisted in C. parvum/LPS mice appeared to
      influence their ability to mount a NO2-/NO3- response subsequent to the LPS
      challenge. The NO2-/NO3- response did not contribute to lethality in C.
      parvum/LPS mice because anti-TNF-alpha and anti-IFN-gamma mAbs were protective
      but had no effect on serum NO2-/NO3- levels when administered to mice 24 h before
      the LPS challenge.

PMID- 9000534
TI  - N-acetyl-L-cysteine-induced up-regulation of HIV-1 gene expression in monocyte
      derived macrophages correlates with increased NF-kappaB DNA binding activity.
AB  - Nuclear factor kappaB (NF-kappaB) is an important cellular regulator of human
      immunodeficiency virus (HIV) gene expression. In T cells, N-acetyl-L-cysteine
      (NAC) inhibits the induction of NF-kappaB and transcription of HIV-1. However,
      NAC up-regulates HIV-1 replication in monocyte-derived macrophages (MDM). In this
      study we demonstrate that NAC treatment of MDM transfected with a chloramphenicol
      acetyltransferase (CAT) construct under transcriptional control of the HIV-1 long
      terminal repeat resulted in an up-regulation of CAT activity. Furthermore, MDM
      transfected with a HIV-1-NF-kappaB-CAT construct also produced increased CAT
      activity after NAC treatment. In addition, electrophoretic mobility shift assays
      revealed that nuclei of NAC-treated MDM contained increased binding activity to
      wild-type, but not mutant, kappaB oligonucleotides. Components of the binding
      activity were identified with antibodies as the NF-kappaB subunits p50 and p65.
      These data indicate that NAC-induced enhancement of HIV-1 replication in MDM is
      regulated at the level of viral gene expression and mediated by NF-kappaB.

PMID- 9000535
TI  - Analysis of leukocyte activation during acute rejection of pulmonary allografts
      in noninfected and cytomegalovirus-infected rats.
AB  - After human lung transplantation acute rejection and cytomegalovirus (CMV)
      infections may occur, probably contributing to the development of chronic
      rejection. We established a model of subacute allograft rejection in rats to
      analyze leukocyte activation and effects of a CMV infection. Histoincompatible
      lung transplants (BN/LEW) without immunosuppression (group A) and lungs of
      initially immunosuppressed animals (group B) were analyzed. The production of
      inflammatory mediators (interleukin-6, tumor necrosis factor alpha, nitric
      oxides) and the expression of MHC class II antigens by alveolar and lung tissue
      macrophages were significantly enhanced during the alloresponse. In recipients
      without immunosuppression (group A) allograft necrosis was detected by day 6,
      whereas group B allografts were fully rejected by day 25. In allografts of
      immunosuppressed, CMV-infected animals (group C) the CMV infection was clearly
      aggravated and the number of activated lung tissue macrophages was increased when
      compared with noninfected allografts or isografts. The subacute model provides
      the advantage of allowing us to study mechanisms of acute rejection without the
      effects of reperfusion injury. Furthermore these findings underline the role of
      inflammatory mediators produced by macrophages during rejection.

PMID- 9000536
TI  - Growth-inhibitory and apoptosis-inducing activities of calprotectin derived from
      inflammatory exudate cells on normal fibroblasts: regulation by metal ions.
AB  - We have shown previously that a calcium-binding protein complex, calprotectin,
      derived from polymorphonuclear leukocytes exerts a cytostatic and cytolytic
      effect against a very broad range of tumor cell lines. We also described that
      calprotectin is an apoptosis-inducing factor for certain tumor cells and that
      zinc ion attenuates the calprotectin activities. The titers of the factor in body
      fluids are known to increase greatly in various types of inflammation. In this
      study, to learn the role of calprotectin in inflammation, the growth-inhibitory
      and the apoptosis-inducing activities of the factor against normal fibroblasts
      were examined because fibroblasts are a cell type constituting a local
      inflammatory site. Rat calprotectin inhibited the growth of murine embryonic as
      well as human dermal fibroblasts. Although calprotectin induced apoptotic
      morphology in both fibroblasts, the reaction was slower and less efficient than
      cases using tumor cells as targets. The activities were significantly abrogated
      by 10-50 microM Zn2+, Cu2+, Mn2+, or Fe2+, respectively, whereas the trivalent
      cations Al3+ and Fe3+ had no effect. The dose-response curves of the calprotectin
      effects were shifted to about 10-fold lower concentration ranges in the divalent
      metal ion-depleted medium. These results suggest that calprotectin
      extracellularly affects the inflammatory processes by modulating the growth and
      survival states of normal fibroblasts, and that the effects are physiologically
      controlled by several metal ions.

PMID- 9000537
TI  - Chemotaxis by human neutrophils and their cytokineplasts treated with inhibitors
      of nitric oxide synthase: no suppression of orientation or trajectory.
AB  - Inhibitors of nitric oxide (NO) synthase are reported to inhibit both the
      adherence of polymorphonuclear leukocytes (PMN) to substrate and chemotaxis
      (directed locomotion) of PMN as determined in Boyden chamber assays. In the
      current study, we examined both human blood PMN and granule-poor motile
      cytoplasts derived from them (cytokineplasts, CKP), under direct microscopic
      observation with concomitant time-lapse video recording, for their ability to
      respond chemotactically to an erythrocyte destroyed by laser microirradiation. In
      this system we can observe directly and continuously the orientation and
      trajectory of PMN before, during, and after establishment of a chemotactic
      gradient. For both PMN and CKP we employed three different inhibitors of NO
      synthase (N(omega)-methyl-L-arginine, N-iminoethyl-L-ornithine, and
      diphenyleneiodonium) in at least twice the concentrations employed to inhibit
      chemotaxis of PMN in Boyden chambers or killing of bacteria in CKP. Although
      small differences in adhesion might not have been appreciated, treated PMN and
      CKP were each indistinguishable from untreated controls in their ability to
      orient in a newly created chemotactic gradient and in their trajectories toward
      the chemotactic target.

PMID- 9000538
TI  - Monoclonal antibodies against the human mannose receptor as a specific marker in
      flow cytometry and immunohistochemistry for macrophages.
AB  - Recently we developed mouse monoclonal antibodies (mAb) against the isolated
      human 175-kDa mannose receptor. In the present study we tested whether these mAb
      are suitable for the detection of the mannose receptor on cultured macrophages
      using flow cytometry and on cells in human tissues using immunohistochemistry.
      Human monocytes did not react with the mAb in flow cytometry. Mannose receptor
      expression became detectable on monocytes cultured for 3 days (macrophages), and
      was maximal from 4 days onward. The mannose receptor was up-regulated on
      dexamethasone-treated (immunosuppressed) macrophages, and down-regulated on
      lipopolysaccharide-treated (activated) macrophages. Immunohistochemically the
      staining pattern of our mAb was compared with the marker of monocytes/macrophages
      KP1. In a bone marrow smear, only macrophages were stained with our mAb, whereas
      all myeloid cells were stained with KP1. In the thymus and lymph node, mannose
      receptor-positive branched cells (macrophages and dendritic cells) were detected
      in connective tissue, thymus cortex (not medulla), and in the T cell area (not
      the B cell area) of lymph nodes, whereas KP1 stained branched cells in all areas.
      It was concluded that the mAb are useful tools in flow cytometry and
      immunohistochemistry for the specific detection of cells expressing mannose
      receptor.

PMID- 9000539
TI  - Cathepsin G binds to human lymphocytes.
AB  - Cathepsin G is a serine protease located in the azurophil granules of
      neutrophils. We have shown previously that cathepsin G stimulates human
      lymphocytes. In this study, we demonstrate that cathepsin G exhibits specific,
      saturable and reversible binding to lymphocytes: B cells, CD4+ T cells, CD8+ T
      cells, and natural killer (NK) cells. Phenylmethylsulfonyl fluoride (PMSF) 
      inhibited cathepsin G also bound to lymphocytes, although both the number of
      binding sites and the affinity were less than those of native cathepsin G. The
      binding of cathepsin G to lymphocytes showed cooperativity, but that of PMSF
      inhibited cathepsin G did not. PMSF-inhibited cathepsin G was able to partially
      displace bound cathepsin G. These results suggest that molecules on the
      lymphocyte surface that bind cathepsin G recognize not only the active site of
      cathepsin G but also other sites of this molecule, but the active site has an
      important function in this binding because stimulation of lymphocytes requires
      the binding of proteolytically active cathepsin G.

PMID- 9000540
TI  - Regulation of T cell-dependent and -independent IL-12 production by the three Th2
      type cytokines IL-10, IL-6, and IL-4.
AB  - The production of IL-12 by macrophages/dendritic cells (Mphi/DC) is mediated
      either by a T cell-dependent pathway that is induced primarily by the interaction
      of CD40 ligand (CD40L) on activated T cells with CD40 on IL-12-producing cells or
      by a T cell-independent pathway that is induced by bacteria or bacterial products
      and enhanced by interferon-gamma (IFN-gamma). In this study we investigated the
      ability of the Th2-type cytokines interleukin (IL)-10, IL-6, and IL-4 to modulate
      IL-12 production in Mphi/DC induced through the two pathways. IL-12 production
      was induced in Mphi/DC from normal mice by stimulation with the combination of
      IFN-gamma plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan I (a model
      for the T cell-independent pathway) or by co-culture with Chinese hamster ovary
      (CHO) cells transfected with the CD40L (a model for the T cell-dependent
      pathway). The effects of three Th2-type cytokines on IL-12 production by Mphi/DC
      through the two pathways were examined. IL-10 inhibited IL-12 production induced
      through both pathways, although the inhibitory effect was more potent on the (IFN
      gamma + LPS)-induced pathway. IL-6 inhibited only (LPS + IFN-gamma)-induced IL-12
      production. The effect of IL-4 was particularly noteworthy: this cytokine
      inhibited (LPS + IFN-gamma)-induced IL-12 production, whereas it potentiated the
      production of IL-12 induced by CD40L. Regulation of IL-12 protein production by
      IL-10 and IL-4 was found to correspond to the levels of mRNA accumulation for the
      p40 and p35 IL-12 genes, whereas the presence of IL-6 during stimulation
      decreased IL-12 protein production without affecting steady-state mRNA levels.
      These results indicate that IL-12 production in Mphi/DC induced through a T cell
      dependent or -independent pathway is positively or negatively regulated by
      particular cytokines at various control levels.

PMID- 9000542
TI  - Expression of the human NRAMP1 gene in professional primary phagocytes: studies
      in blood cells and in HL-60 promyelocytic leukemia.
AB  - In the mouse, mutations at the natural resistance-associated macrophage protein 1
      (Nramp1) gene abrogate resistance to infection with antigenically unrelated
      intracellular parasites such as Mycobacterium, Salmonella, and Leishmania. Nramp1
      expression is restricted to reticuloendothelial organs and peripheral blood
      leukocytes, where the protein may function as a membrane transporter of an as yet
      to be identified substrate. To identify the human blood cell type(s) expressing
      NRAMP1 mRNA and determine how Nramp1 expression is regulated in these cells, we
      have examined separated populations of peripheral blood leukocytes and in vitro
      cell lines. We observed that polymorphonuclear leukocytes (PMN) are the major
      site of NRAMP1 expression, followed to a lesser degree by monocytes (MN).
      Migration of MN to tissues (alveolar macrophages) or maturation in vitro (long
      term culture) was associated with a higher level of NRAMP1 expression compared
      with blood MN. Northern analyses of RNA from model cultured cells showed absence
      of NRAMP1 expression in transformed cell lines from either erythroid or lymphoid
      T or B lineages as well as progenitors of the monocyte/macrophage pathway (KG1,
      U937, THP1), and the HL-60 promyelocytic leukemia. Induction of differentiation
      of HL-60 cells toward either the monocyte/macrophage (vitamin D3, phorbol ester)
      or the granulocyte pathways (DMF, DMSO), as measured by induction of IL8-Rb, c
      FMS, and CD14 marker gene expression, was concomitant with a strong induction of
      NRAMP1 expression. These results suggest that NRAMP1 expression is specific to
      the myeloid lineage and is acquired during the maturation of PMN and MN. The
      possibility that NRAMP1 may be a component of the phagosomal/endosomal apparatus
      common to PMN and MN is discussed.

PMID- 9000541
TI  - LPS pretreatment reprograms macrophage LPS-stimulated TNF and IL-1 release
      without protein tyrosine kinase activation.
AB  - Pretreatment of macrophages with low-dose endotoxin (LPSp) profoundly alters
      cytokine release in response to subsequent LPSa activation. These qualitative and
      quantitative alterations in cytokine release have been termed macrophage
      reprogramming. Macrophage activation by LPS is thought to occur via a mechanism
      involving an early protein tyrosine kinase (PTK) phosphorylation step. PTK
      inhibition with genistein or herbimycin A blocks LPSa-stimulated secretion of
      tumor necrosis factor (TNF) and interleukin-1 (IL-1). In this study we
      investigated whether a PTK pathway participates in LPSp pretreatment
      reprogramming. We show that LPSp pretreatment inhibited TNF and augmented IL-1
      release in response to subsequent LPSa stimulation. Blockade of PTK activation
      pathways during the interval when macrophages were exposed to LPSp prevented
      mitogen-activated protein kinase phosphorylation, as well as LPSp-stimulated
      release of TNF and IL-1, but did not block LPSp reprogramming effects. We
      conclude that LPSp pretreatment reprogramming of macrophage cytokine production
      does not require PTK activation.

PMID- 9000543
TI  - Augmented expression of platelet-activating factor receptor gene by TNF-alpha
      through transcriptional activation in human monocytes.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a cytokine produced by activated
      monocytes and often associated with platelet-activating factor (PAF) during the
      pathogenesis of many inflammatory and infectious diseases. PAFR is a G-protein
      coupled receptor constitutively expressed on monocytes. TNF-alpha (100-400 U/mL)
      significantly increased PAFR mRNA expression in human monocytes. This increase
      was seen after 1 h of stimulation and persisted up to 24 h. Actinomycin D
      pretreatment studies revealed a transcriptional increase in PAFR gene expression
      without effect on mRNA half-life. [3H]WEB 2086 binding studies showed a
      significant (43%) increase in specific binding sites in 24-h-treated cells
      without change in receptor affinity. Increased interleukin-6 production in
      response to PAF was also found in 24-h TNF-alpha-pretreated monocytes. These
      observations provide new evidence for TNF-alpha and PAF interactions in human
      monocytes during inflammatory processes through up-regulation of PAFR expression
      by TNF-alpha.

PMID- 9000544
TI  - Characterization of the processing and granular targeting of human proteinase 3
      after transfection to the rat RBL or the murine 32D leukemic cell lines.
AB  - Proteinase 3 (PR3) is a neutrophil serine protease stored in the azurophil
      granules of the promyelocyte and its successors. The protease has been identified
      as an autoantigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) occurring
      in patients with Wegener's granulomatosis. To characterize the biosynthesis and
      processing of human PR3 in a transgenic cellular model, cDNA encoding human pre
      proproteinase 3 cloned from U-937 cells was transfected to the rat
      basophilic/mast cell line RBL-1 and the murine myeloblast-like cell line 32D c13.
      The stable expression of transgenic proteinase 3 was characterized by
      biosynthetic labeling, followed by immunoprecipitation, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and fluorography. After pulse labeling for 30
      min two proforms of PR3 (32 and 35 kDa), differing in carbohydrate content but
      with protein cores of identical size, were demonstrated. Chase of the label
      resulted in a processed 32-kDa form clearly visible in RBL, but only faintly in
      32D cells, probably indicating delayed intracellular transfer in the latter cell
      line. Partial digestion with N-glycosidase F showed that both potential N
      glycosylation sites on PR3 were occupied and conversion of the oligosaccharide
      side chains into complex forms was demonstrated by acquisition of resistance to
      endoglycosidase H. Translocation of PR3 to granules was shown by subcellular
      fractionation and immunocytochemistry. Enzymatic activation of PR3 was suggested
      by affinity to diisopropylfluorophosphate and removal of an amino-terminal
      propeptide. Cells transfected with PR3 showed positive immunofluorescence for
      ANCA-containing sera from patients with Wegener's granulomatosis. Our results
      show that human PR3 transfected to RBL or 32D cells is synthesized as a 29-kDa
      protein core glycosylated on two distinct sites. Oligosaccharide trimming and
      proteolytic processing occur and the protein is targeted for granular storage in
      a form antigenic for ANCA.

PMID- 9000545
TI  - Pathogenetic mechanisms in nephrotoxic acute renal failure.
AB  - Despite marked variations in the chemical nature of nephrotoxic agents, most
      probably trigger lethal tubular injury via activation of a limited number of
      pathogenetic pathways. Elucidation of these pathways has been an area of intense
      investigation, with the hope that the knowledge obtained might lead to new
      interventions for preventing acute renal failure. The roles of altered cellular
      energetics, oxidant stress, cellular calcium overload, and deranged phospholipid
      homeostasis have undergone intense scrutiny. Recently, the participation of
      cytoskeletal rearrangements and apoptosis have been increasingly assessed. The
      purpose of this article is to provide a brief overview of this broad and evolving
      area of investigation.

PMID- 9000546
TI  - Contrast media-associated nephrotoxicity.
AB  - Contrast media-associated nephrotoxicity (CM-AN) continues to be a common cause
      of hospital-acquired acute renal failure. This review of CM-AN discusses the
      pathogenesis, clinical features, incidence, risk factors with an emphasis on pre
      existing renal insufficiency and diabetes mellitus, volume of contrast media, low
      osmolar versus high osmolar contrast media, and prophylaxis. Although the
      literature contains an abundance of information concerning CM-AN, areas of
      uncertainty remain in respect to clinical significance, risk with modem day
      radiological techniques and contrast media, optimal prophylactic regimens, and
      criteria for creatinine screening before contrast media administration.

PMID- 9000547
TI  - Aminoglycoside nephrotoxicity.
AB  - Aminoglycoside antibiotics maintain a leading role in antibacterial therapy of
      severe gram-negative infections despite nephrotoxicity complicating 10% to 20% of
      therapeutic courses. Risk factors for aminoglycoside-induced renal injury have
      been identified. A variety of maneuvers to protect renal function and minimize
      toxicity have been suggested, but few have been accepted for clinical use.
      Aminoglycosides are eliminated by glomerular filtration, but a fraction is
      reabsorbed in the proximal tubule. Polycationic aminoglycosides bind to anionic,
      brush-border, phospholipid membranes and are transported intracellularly.
      Disruption of normal phospholipid trafficking within the cell is evidenced by the
      presence of myeloid bodies, electron-dense concretions of phospholipid material.
      Although consistent with aminoglycoside injury, such biochemical and histological
      changes are observed with other drug exposures in which renal failure does not
      occur. Therapeutic drug monitoring services have failed to reduce aminoglycoside
      toxicity over the years, although two pharmacological parameters are imperative.
      The first is that peak aminoglycoside levels correlate with efficacy, as these
      agents display concentration-dependent bacterial killing. Second, trough levels
      reflect nephrotoxicity; the kidney is unable to excrete the dose of
      aminoglycoside within the dosing interval owing to impaired function. These two
      points have led to numerous reports evaluating once-daily dosing of
      aminoglycosides in which the cumulative dose for a 24-hour period would be
      administered as a single dose. This would take advantage of concentration
      dependent "bug" killing as well as the post-antibiotic effect while minimizing
      repeated exposure and potential nephrotoxicity. Further trials are warranted to
      establish specific guidelines for once-daily as well as every 36- to 48-hour
      dosing regimens in patients with established renal impairment for specific
      organisms and specific types of infection.

PMID- 9000548
TI  - Nephrotoxicity of immunosuppressive drugs: experimental and clinical
      observations.
AB  - Cyclosporine has improved patient and graft survival rates in solid organ
      transplantation since its introduction in 1976, and has been increasingly applied
      with considerable clinical benefit in the treatment of autoimmune diseases.
      However, the therapeutic benefits of immunosuppressive therapy for
      transplantation and autoimmune indications have been frequently limited by the
      occurrence of acute and chronic nephrotoxicity, which is the most obvious common
      side effect. Cyclosporine nephrotoxicity therefore remains an important clinical
      challenge. The clinical aspects and pathophysiology of nephrotoxicity induced by
      current and future immunosuppressive drugs are reviewed in this article, with an
      emphasis on the studies of chronic cyclosporine nephropathy, which is
      characterized by a decrease in glomerular filtration rate, afferent
      arteriolopathy, and striped tubulointerstitial fibrosis. Insights gained from
      experimental models of chronic nephrotoxicity associated with tubulointerstitial
      fibrosis and arteriolopathy are presented to elucidate the pathophysiology. Thus,
      experimental and clinical data regarding tacrolimus (FK506) and sirolimus
      (rapamycin) are presented.

PMID- 9000549
TI  - Occupational and environmental renal disease.
AB  - Occupational renal diseases provide models for understanding environmental renal
      diseases. Kidney damage in a few workers induced by heavy exposure to
      identifiable toxins indicates what to expect among the large population exposed
      to low levels of toxins dispersed in the larger environment. Occupational and
      environmental renal diseases present a unique opportunity for primary prevention
      as well as the diagnostic challenge of long latency and multifactorial etiology.
      The occupational and environmental toxins that cause chronic renal disease
      include the heavy metals (Pb, Cd, Hg, As, Cr, U), organic compounds sometimes
      referred to as solvents, silica, and beryllium. Toxins encountered as medicinal
      agents such as germanium, gold, and aluminum will not be considered. This review
      will update major contributions to the subject which have appeared over the past
      half decade.

PMID- 9000550
TI  - Renal toxicities of antineoplastic drugs and bone marrow transplantation.
AB  - A number of antineoplastic chemotherapeutic drugs may produce fluid and
      electrolyte disturbances or nephrotoxic reactions extending across the clinical
      spectrum, from subclinical renal dysfunction to progressive chronic renal
      insufficiency to severe acute failure. Although some of the drugs that are highly
      nephrotoxic are now seldom used, others are tremendously useful in modern
      clinical oncology. Some newer antineoplastic therapies such as interleukin-2 and
      bone marrow transplantation are commonly associated with nephrotoxicity. Although
      our understanding of the pathophysiological mechanisms underlying these toxic
      reactions is still rather rudimentary, information derived from animal models,
      coupled with clinical experience, has in many circumstances generated clinical
      interventions that can successfully limit treatment-related renal injury.

PMID- 9000551
TI  - Renal failure related to angiotensin-converting enzyme inhibitors.
AB  - The introduction of agents that block the renin-angiotensin system has provided
      major benefit to patients with hypertension, renal diseases, and congestive heart
      failure. Some of the therapeutic advantages related to the kidney derive from
      removing angiotensin II at the efferent arteriole. Under some circumstances when
      afferent blood supply is compromised, particularly beyond a renal arterial
      stenosis, use of angiotensin-converting enzyme (ACE) inhibitors can lead to
      decrements of glomerular filtration rate (GFR) and impaired potassium excretion,
      which clinicians should be prepared to identify and manage. How often this occurs
      and when such a decrement poses a hazard to renal parenchymal viability depends
      on the starting conditions of the renal vasculature and sodium balance. Although
      these observations have been made primarily with ACE inhibitors, the basic
      principles apply to other agents interacting with components of the renin
      angiotensin system, including angiotensin II antagonists and renin-inhibitors.
      When promptly identified and treated, changes in kidney function under these
      conditions represent a modest and acceptable risk worth taking in exchange for
      major therapeutic benefits.

PMID- 9000552
TI  - The prostate: a target for carcinogenicity of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) derived from cooked foods.
AB  - Prostate tissues obtained from rats given a food-derived carcinogen, 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), at a dose of 400 ppm in the diet
      for 52 weeks were histopathologically evaluated and found to contain prostate
      carcinomas limited to the ventral lobe in 18 of 27 cases. Atypical hyperplasias
      were also detected in the ventral and anterior prostate as well as the seminal
      vesicles. 32P-Postlabeling analysis of DNA demonstrated that PhIP-DNA adducts are
      produced in all lobes of the prostate of rats receiving PhIP. The findings
      indicate that PhIP is carcinogenic to rat prostate in addition to the previously
      demonstrated targeting of the colon and mammary glands, providing evidence of a
      possible role of PhIP in human prostate carcinogenesis and highlighting the
      potential importance of PhIP for man.

PMID- 9000553
TI  - Ornithine decarboxylase and polyamines in familial adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP), due to germ-line mutation of the
      adenomatous polyposis coli (APC) gene, is characterized by development of
      colorectal adenomas and ultimately colorectal cancer. The usefulness of ornithine
      decarboxylase (ODC) activity and polyamine levels in normal-appearing colorectal
      mucosa to stratify risk for colorectal neoplasia by discriminating presymptomatic
      individuals with germ-line APC mutation (genotype-positive) from genotype
      negative family controls was evaluated in 36 at-risk subjects undergoing
      endoscopic and genetic screening for FAP. ODC activity and levels of putrescine,
      spermidine, and spermine were significantly higher in presymptomatic genotype
      positive patients compared to genotype-negative persons (P = 0.029, <0.001,
      0.002, and <0.001, respectively). Moreover, a putrescine level with a cutoff
      point of 1.5 nmol/mg protein was the most accurate single discriminator of risk
      status. ODC activity and polyamine levels are significantly elevated in gene
      carriers of FAP before the development of polyposis, suggesting a role for these
      compounds in tumorigenesis of FAP. These assays may be useful in evaluating at
      risk members of FAP families in which mutation of the APC gene cannot be found.

PMID- 9000554
TI  - Induction of melanoma reactive T cells by stimulator cells expressing melanoma
      epitope-major histocompatibility complex class I fusion proteins.
AB  - Several epitopes in the human melanoma antigens recognized by HLA-A2-restricted
      CTLs have a relatively low MHC-binding affinity and as a result may be expressed
      at very low densities on the cell surface, indicating that these epitopes may not
      be efficient immunogens. To express these epitopes at higher densities on the
      surface of antigen-presenting cells and therefore improve their immunogenicity, a
      DNA construct in which a cDNA fragment encoding the melanoma epitope MART-1(27
      35) or gp100(280-288) was inserted between sequences encoding the leader and the
      HLA-A*0201 protein. Cells transfected with these epitope-HLA fusion constructs
      were recognized by HLA-A2-restricted melanoma-reactive CTLs specific for the MART
      1 or gp100 epitope. In addition, tumor-reactive CTLs could be induced from PBMCs
      of patients with metastatic melanoma by in vitro stimulation with HMY-C1R B-cell
      lines expressing the MART-1 or gp100 epitope-HLA-A*0201 fusion protein. These
      epitope-HLA fusion constructs may be useful for the development of
      immunotherapies for patients with melanoma.

PMID- 9000555
TI  - Cell cycle regulation of the human DNA mismatch repair genes hMSH2, hMLH1, and
      hPMS2.
AB  - Hereditary nonpolyposis colorectal cancer is a cancer susceptibility syndrome
      that has been found to be caused by mutations in any of several genes involved in
      DNA mismatch repair, including hMSH2, hMLH1, or hPMS2. Recent reports have
      suggested that hMSH2 and hMLH1 have a role in the regulation of the cell cycle.
      To determine if these genes are cell cycle regulated, we examined their mRNA and
      protein levels throughout the cell cycle in IMR-90 normal human lung fibroblasts.
      We demonstrate that the levels of hMSH2 mRNA and protein do not change
      appreciably throughout the cell cycle. Although hMLH1 mRNA levels remained
      constant, there was a modest (approximately 50%) increase in its protein levels
      during late G1 and S phase. The levels of hPMS2 mRNA fluctuated (decreasing 50%
      in G1 and increasing 50% in S phase), whereas hPMS2 protein levels increased 50%
      in late G1 and S phase. Our data indicate that, at least in normal cells, the
      machinery responsible for the detection and repair of mismatched DNA bases is
      present throughout the cell cycle.

PMID- 9000556
TI  - Repeat expansion detection analysis of (CAG)n tracts in tumor cell lines,
      testicular tumors, and testicular cancer families.
AB  - The mutational expansion of triplet repeat microsatellite sequences underlies the
      transmission of a number of heritable neurological disorders. However, this form
      of microsatellite instability has not previously been observed in association
      with malignant disease. Because trinucleotide expansions can dramatically alter
      gene expression and protein function, we hypothesized that they might occur in
      neoplastic cells as a mechanism through which to alter cancer genes. Accordingly,
      we used the repeat expansion detection technique to determine whether (CAG)n
      triplet repeat expansions were present in DNA from malignant cells. No expansions
      were observed in a survey of 20 tumor cell lines derived from neoplasms of the
      breast, ovary, cervix, endometrium, lung, colon, placenta, or hematopoietic
      system. However, we did observe expanded (CAG)n tracts in DNA from 5 of 11
      testicular tumor cell lines and in 1 of 11 sporadic testicular tumors.
      Examination of the corresponding normal DNA, when available, revealed that some
      of the expansions were germline in nature. To assess the possibility that (CAG)n
      expansions underlie some cases of inherited testicular cancer, we also analyzed
      germline DNA from members of five kindreds predisposed to this malignancy. An
      increase in (CAG)n tract size was observed in all five families and was
      particularly striking in one large pedigree in which expansions were observed in
      three of four affected siblings. These observations raise the possibility that
      the germline transmission of expanded (CAG)n tracts may play a role in testicular
      tumorigenesis.

PMID- 9000558
TI  - Spontaneous apoptosis is inversely related to intratumoral microvessel density in
      gastric carcinoma.
AB  - Increasing evidence from experimental studies indicates that apoptosis may be
      related to angiogenesis in tumor progression. To explore how spontaneous
      apoptosis correlates with tumor angiogenesis, we measured the apoptotic index
      (AI) using the ApopTag kit (Oncor) and intratumoral microvessel density using an
      anti-CD34 monoclonal antibody in 101 cases of gastric carcinoma.
      Immunohistochemical staining for Ki-67 labeling index and the expression of p53
      were conducted simultaneously. Statistical analysis revealed an inverse
      correlation between AIs and intratumoral microvessel densities (r = -0.4066, P <
      0.0001) and failed to find significant correlations between AI and Ki-67 labeling
      index, as well as the expression of p53. The results of this study demonstrated
      for the first time that the incidence of apoptosis in gastric carcinoma is
      significantly influenced by the extent of neovascularization and suggests that
      tumor angiogenesis may contribute to a reduction of apoptosis in tumor cells.

PMID- 9000557
TI  - Id genes encoding inhibitors of transcription are expressed during in vitro
      astrocyte differentiation and in cell lines derived from astrocytic tumors.
AB  - Id proteins belong to a class of nuclear transcription factors known as helix
      loop-helix proteins. It has been reported that Id genes function as negative
      regulators of differentiation, and Id gene expression is down-regulated during
      cell differentiation. We examined the regulation of Id genes during astrocyte
      differentiation in a murine nervous system precursor cell line, NSEHip2-28, which
      is able to differentiate along the astroglial lineage, as well as in human
      astroglial tumor cell lines. Upon induction of NSEHip2-28 differentiation, at a
      time when glial fibrillary acidic protein expression became detectable, the
      expression of all four Id family members initially increased dramatically, and
      subsequently decreased. Furthermore, varying levels of Id gene expression were
      found in astroglial tumor cell lines displaying variable degrees of lineage
      specific differentiation. These results suggest that the expression of Id family
      members may play an important role in the control of astrocyte differentiation.

PMID- 9000559
TI  - Short-chain fructo-oligosaccharides reduce the occurrence of colon tumors and
      develop gut-associated lymphoid tissue in Min mice.
AB  - C57BL/6J-Min/+ mice, which are heterozygous for a non-sense mutation in the Apc
      gene, provide a model for both familial adenomatous polyposis and sporadic colon
      cancers. In our study, gut tumors and small intestine lymphoid nodules were
      counted in Min mice fed fiber-enriched diets for 6 weeks. Neither starch-free
      wheat bran nor resistant starch modified the number of tumors. However, short
      chain fructo-oligosaccharides dramatically reduced the incidence of colon tumors
      and concomitantly developed gut-associated lymphoid tissue. Our experiment shows
      that short-chain fructo-oligosaccharides counteract advanced stages of colon
      carcinogenesis, possibly via stimulation of antitumoral immunity by modulation of
      the colonic ecosystem.

PMID- 9000560
TI  - Bcl2 is the guardian of microtubule integrity.
AB  - We have investigated the ability of several drugs commonly used in the treatment
      of human cancer to induce bcl2 phosphorylation and cell death in human cell lines
      derived from acute leukemia, lymphoma, breast cancer, and prostate cancer. The
      results of this analysis indicate that drugs affecting the integrity of
      microtubules induce bc12 phosphorylation, whereas anticancer drugs damaging DNA
      do not. Comparison of the effects of taxol and its analogue, taxotere, indicates
      that taxotere is capable of inducing bcl2 phosphorylation and apoptotic cell
      death at 100-fold lower concentrations than taxol. Induction of cancer cell death
      through phosphorylation of bcl2 thus provides an opportunity not only for more
      refined targeting of therapeutic drugs but for understanding of an important
      pathway leading to apoptosis. Phosphorylation of bcl2 in drug-treated cancer
      cells occurs in G2-M, the phase of the cell cycle in which this class of drugs is
      active. No induction of bcl2 phosphorylation occurs in chronic lymphocytic
      leukemia cells that overexpress bcl2 but are blocked at G0-G1. Thus, prevention
      of polymerization or depolymerization of cellular microtubules by this class of
      cancer therapeutic drugs causes phosphorylation of bcl2, abrogating the normal
      antiapoptotic function of bcl2 and initiating the apoptotic program in the
      cycling cancer cells; these results are consistent with a normal physiological
      role of bcl2 as "guardian of microtubule integrity."

PMID- 9000561
TI  - Comparative molecular field analysis-based predictive model of structure-function
      relationships of polyamine transport inhibitors in L1210 cells.
AB  - Maintenance of intracellular polyamine concentrations necessary for cell growth
      and proliferation is regulated in part by an energy-dependent polyamine uptake
      system. To obtain information on the characteristics of the polyamine uptake
      system in L1210 leukemia cells, we have applied computational chemistry
      techniques to the study of relationships between structure and function of 57
      polyamine analogues. Ki values of polyamine analogues, derived from competitive
      inhibition of [3H]spermidine transport into L1210 cells, were chosen as the
      measure of biological activity. Using comparative molecular field analysis
      (CoMFA), a model was constructed to relate molecular structure with biological
      activity. The model was based on 4 monocationic, 8 dicationic, 14 tricationic,
      and 20 tetracationic polyamine analogues with a range of Ki values for the
      inhibition of [3H]spermidine uptake of 0.97-521 microM. The CoMFA model
      successfully predicted the inhibitory potency of 11 polyamines that had not
      previously been tested for polyamine uptake inhibitory activity. The 11 values
      predicted were within 33 +/- 62% of the actual Ki values. The test group included
      aziridinyl diamines, acetylated spermidines, two new oxazolidinonyl spermidines,
      monoaziridinyl spermidines, and a diaziridinyl spermine. Several of the compounds
      from this test group have been shown to have anticancer activity in mice.
      Consistent with the CoMFA model, certain basic functional groups, such as
      aziridines that have pKa values in the range of 6-7, seem to interact with the
      polyamine transporter in a cationic form. The results suggest that the CoMFA
      model is useful in drug design strategies as a predictive tool for the discovery
      of new anticancer agents that utilize a polyamine transporter for cellular
      uptake.

PMID- 9000562
TI  - Mapping of the molecular determinants involved in the interaction between eps15
      and AP-2.
AB  - eps15, a substrate for the epidermal growth factor receptor and other receptor
      tyrosine kinases, possesses a discrete domain structure with protein-binding
      properties. It interacts with a number of cellular proteins through an
      evolutionarily conserved protein-binding domain, the eps15 homology domain,
      located in its NH2-terminal region. In addition, a proline-rich region, located
      in the COOH-terminal portion of eps15, can bind to the Src homology 3 domain of
      the crk proto-oncogene product in vitro. Recently, coimmunoprecipitation between
      eps15 and AP-2, a major component of coated pits, was reported. Here, we
      characterize the molecular determinants of the eps15/AP-2 interaction. The AP-2
      binding region of eps15 is localized in its COOH-terminal region and spans
      approximately 80 amino acids. At least three molecular determinants, located at
      residues 650-660, 680-690, and 720-730, are involved in the binding. AP-2 binds
      to eps15 through its alpha subunit (alpha-adaptin); in particular, the COOH
      terminal region of alpha-adaptin, the so-called alpha-ear, contains the eps15
      binding region.

PMID- 9000563
TI  - Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats
      by flavonoids diosmin and hesperidin, each alone and in combination.
AB  - The modifying effects of the two flavonoids diosmin and hesperidin given during
      the initiation and postinitiation phases of oral carcinogenesis initiated with 4
      nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The compounds
      were tested alone and in combination. At 6 weeks of age, animals were divided
      into experimental and control groups and fed diets containing 1000 ppm diosmin
      and 1000 ppm hesperidin and a diet containing both compounds (900 ppm diosmin and
      100 ppm hesperidin). At 7 weeks of age, all animals except those treated with
      each test chemical alone and control groups were given 4-NQO (20 ppm) in the
      drinking water for 8 weeks to induce oral cancer. Starting 7 days before the 4
      NQO exposure, groups of animals were fed the diets containing test chemicals for
      10 weeks and then switched to the basal diet. Starting 1 week after the cessation
      of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the
      diets containing diosmin, hesperidin, or diosmin combined with hesperidin and
      maintained on these diets for 22 weeks. The other groups consisted of rats given
      diosmin (1000 ppm), hesperidin (1000 ppm), and the combination regimen of these
      two compounds (900 ppm diosmin with 100 ppm hesperidin) alone, and untreated
      rats. All animals were necropsied at the termination of the study (week 32). The
      incidences of tongue lesions (neoplasms and preneoplasms), polyamine levels in
      the tongue tissue, and cell proliferation activity estimated by a 5
      bromodeoxyuridine-labeling index and by morphometric analysis of silver-stained
      nucleolar organizer regions protein were compared among the groups. Feeding of
      both compounds singly or in combination during the initiation phase caused a
      significant reduction in the frequency of tongue carcinoma [diosmin, 68%
      reduction (P < 0.01); hesperidin, 75% reduction (P < 0.005); and the combination
      regimen, 69% (P < 0.05)]. When fed the test compounds singly or the combination
      regimen after 4-NQO exposure, the frequency of tongue cancer was also decreased
      [diosmin, 77% reduction (P < 0.005); hesperidin, 62% reduction (P < 0.05); and
      the combination regimen, 77% (P < 0.005)]. The incidences of oral preneoplasia
      (hyperplasia and dysplasia) in these groups were also decreased when compared
      with carcinogen controls (P < 0.05-P < 0.001). There were no pathological
      alterations in rats treated with test compounds or the combined regimen alone or
      those in an untreated control group. Dietary administration of these compounds
      significantly decreased the expression of cell proliferation biomarkers (5
      bromodeoxyuridine-labeling index and silver-stained nucleolar organizer regions
      protein number) of the nonlesional tongue squamous epithelium (P < 0.05). Also,
      polyamine concentrations in the oral mucosa were lowered in rats given the
      carcinogen and test compounds, alone and in combination, compared with those of
      rats given 4-NQO alone (P < 0.05). These findings suggest that supplementation
      with the flavonoids diosmin and hesperidin, individually and in combination, is
      effective in inhibiting the development of oral neoplasms induced by 4-NQO, and
      such inhibition might be related to suppression of increased cell proliferation
      caused by 4-NQO in the oral mucosa.

PMID- 9000564
TI  - Dietary fat and colon cancer: modulating effect of types and amount of dietary
      fat on ras-p21 function during promotion and progression stages of colon cancer.
AB  - Although epidemiological and experimental studies have indicated a strong
      relationship between types and amount of dietary fat and colon tumorigenesis, the
      modulating effects of these nutritional factors at the molecular level have not
      been fully elucidated. Transforming proteins encoded by activated ras genes have
      been implicated in the etiology of many human malignancies, including colon
      cancer. It is now well established that the transforming ability of ras-p21
      critically depends on its correct localization in plasma membrane. The
      posttranslational processing of the cytosolic precursor (pro-ras), as it is
      synthesized in the cytoplasm, and its proper anchorage to the cytoplasmic face of
      plasma membrane are determined by an important intermediate metabolite of dietary
      fat and an enzyme system that includes farnesyl protein transferase. To provide
      an understanding of the molecular basis of the relationship between the types and
      amount of dietary fat and the transforming function of ras, especially during the
      stages of promotion and progression of colon tumor development, we investigated
      the effect of various types and amount of dietary fat on the expression of ras
      p21 during azoxymethane (AOM)-induced colon carcinogenesis. Male F344 rats were
      fed the semipurified American Institute of Nutrition-76A diet containing low-fat
      corn oil and were given s.c. injections of AOM dissolved in normal saline at a
      dose rate of 15 mg/kg body weight, once weekly, for 2 weeks. Control animals
      received s.c. injections of equal volumes of normal saline. Beginning 1 day after
      the second AOM or saline injection, groups of animals intended for the treatment
      with different types of high-fat dietary regimens were fed the semipurified
      American Institute of Nutrition-76A diets containing high levels of high-fat corn
      oil (HFCO) rich in omega-6 fatty acids or high levels of high-fat fish oil (HFFO)
      rich in omega-3 fatty acids; the remaining animals in experimental and control
      groups were continued on the low-fat corn oil diet until termination of the
      experiment. Groups of animals were sacrificed 1, 12, or 36 weeks after the last
      AOM or saline injection, and their colonic mucosa and grossly visible colon
      tumors from rats sacrificed 36 weeks after the last AOM injection were analyzed
      for the levels of expression of ras-p21. We found that AOM induced increasingly
      higher levels of ras-p21 expression with advancing stages of colon tumor
      development. The HFCO diet resulted in enhanced expression of AOM-induced ras-p21
      as observed 36 weeks after the last AOM injection. In contrast, feeding the HFFO
      diet inhibited AOM-induced ras-p21 expression. These results correlate with
      increased incidence and multiplicity of grossly visible colon tumors in AOM
      treated animals fed a HFCO diet versus decreased incidence and lower multiplicity
      of colon tumors in their counterparts on the HFFO diet. Further analysis of ras
      p21 levels in cytosol and plasma membrane revealed that feeding a HFFO diet
      resulted in increasing accumulation of ras-p21 in cytoplasm with a concomitant
      decrease in membrane-bound ras-p21 levels as observed in animals sacrificed 12
      and 36 weeks after the last AOM injection. Thus, the dietary HFCO may promote
      colon tumorigenesis by increasing ras-p21 expression, whereas HFFO appears to
      exert its antitumor activity by interfering with posttranslational modification
      and membrane localization of ras-p21.

PMID- 9000565
TI  - Evidence for an important role of DNA pyridyloxobutylation in rat lung
      carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: effects of dose
      and phenethyl isothiocyanate.
AB  - The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK), selectively induces lung tumors in F344 rats. NNK is metabolically
      activated to intermediates that methylate and pyridyloxobutylate DNA. To explore
      the importance of pyridyloxobutyl DNA adducts in NNK-induced rat lung
      tumorigenesis, the first study in this report examined levels of these adducts in
      whole lung and pulmonary cells of F344 rats treated with different doses of NNK
      (0.3, 1.0, 10.0, and 50 mg/kg; 3 x weekly for 2 weeks). Pyridyloxobutyl DNA
      adducts were highest in Clara cells compared to alveolar Type II cells, alveolar
      macrophages, and small cells, suggesting that enzymes involved in the formation
      of the pyridyloxobutylating species are concentrated in Clara cells. When we
      compared lung tumor incidence at the different doses of NNK (S. A. Belinsky et
      al., Cancer Res., 50: 3772-3780, 1990) versus pyridyloxobutyl DNA adducts in Type
      II cells, we observed a significant correlation. Because NNK-induced lung tumors
      arise from the Type II cells, this suggests an important role for pyridyloxobutyl
      DNA adducts. In the second study presented in this report, we examined the effect
      of dietary phenethyl isothiocyanate (PEITC), an inhibitor of lung tumor induction
      in F344 rats by NNK, on O6-methyldeoxyguanosine (O6-mG) and pyridyloxobutyl DNA
      adducts in whole lung and lung cells of F344 rats treated with NNK. F344 rats
      were fed control or PEITC-containing diets (3 micromol/g diet) before and
      throughout NNK treatment (1.76 mg/kg, three times weekly for 4, 8, 12, 16, or 20
      weeks). PEITC inhibited formation of pyridyloxobutyl DNA adducts in whole lung
      and all lung cells except macrophages. There was also inhibition of O6-mG, but it
      varied with cell type and length of NNK treatment. Overall, PEITC treatment
      decreased pyridyloxobutyl DNA adducts by 57% in Clara cells, 51% in Type II
      cells, 40% in small cells, and 44% in whole lung. PEITC treatment decreased O6-mG
      levels by 52% in Clara cells, 19% in Type II cells and small cells, and 36% in
      whole lung. These results support the hypothesis that PEITC inhibition of NNK
      induced lung tumors is a result of decreased metabolic activation and DNA binding
      of NNK. The 50% reduction of pyridyloxobutyl DNA adducts in Type II cells agreed
      well with the 50% reduction of NNK-induced lung tumors by PEITC. Because NNK
      induced tumors arise from Type II cells, these results suggest an important role
      for pyridyloxobutyl DNA adducts in NNK-induced rat lung tumorigenesis.

PMID- 9000566
TI  - Sulfone metabolite of sulindac inhibits mammary carcinogenesis.
AB  - Sulindac sulfoxide, a commonly prescribed anti-inflammatory drug, has cancer
      chemopreventive activity. During its metabolism, the inactive prodrug sulindac
      sulfoxide undergoes either reduction to the active anti-inflammatory metabolite
      sulindac sulfide or irreversible oxidation to sulindac sulfone, which lacks
      prostaglandin synthetase inhibitory activity. Interestingly, sulindac sulfone has
      been reported to have cancer chemopreventive activity. The objective of the
      experiments reported here was to investigate the chemopreventive activity of
      sulindac sulfone against mammary carcinogenesis and to study its mechanism. Rats
      were injected with either 12.5 or 37.5 mg of 1-methyl-1-nitrosourea (MNU)/kg body
      weight at 50 days of age. Sulindac sulfone was incorporated into a purified diet
      at a concentration of either 0.03 or 0.06% (w/w) and fed to rats beginning 7 days
      after the injection of MNU. Sulindac sulfoxide at a level of 0.06% (w/w) was fed
      as a reference for comparison. Thirty rats were assigned to each dietary group
      treated with the high dose of MNU, and 44 rats were assigned to each dietary
      group treated with the low dose of MNU. The sulfone reduced cancer incidence and
      the number of cancers per rat irrespective of the dose of MNU injected, and its
      chemopreventive activity was comparable to that of sulindac sulfoxide. Cancer
      latency was also prolonged significantly by sulindac sulfone; the effect was
      particularly notable at the low dose of carcinogen, at which the prolongation of
      latency was >8 weeks. The sulfone inhibited the occurrence of mammary carcinomas
      that were classified as having either a wild-type or a mutant codon 12 in the Ha
      ras gene; however, the inhibitory effect was greater against carcinomas with a
      mutant Ha-ras genotype. Using a mammary gland organ culture transformation assay,
      it was observed that sulindac sulfone also inhibited the formation of 7,12
      dimethylbenz(a)anthracene-induced hyperplastic alveolar nodules and that the
      inhibitory activity of the sulfone was comparable to that of the sulfoxide. These
      data indicate that the observed effect of the sulfone on mammary carcinogenesis
      in vivo is likely to be due to a tissue-specific effect rather than to other
      systemic effects. The findings that both the prodrug and the sulfone inhibited
      carcinogenesis in vivo and nodule formation in organ culture and that the sulfone
      lacks inhibitory activity on prostaglandin synthesis suggest a mechanism(s) of
      chemoprevention that is independent of the prostaglandin pathway. A candidate
      mechanism for the apparent clonal selection pressure exerted by the sulfone
      against mammary carcinogenesis is apoptosis. To test this hypothesis, MCF-7 cells
      were exposed to a range of concentrations of sulindac sulfone and sulfoxide. Both
      compounds inhibited cell growth and induced apoptosis in the absence of necrosis.
      Collectively, these data support a specific chemopreventive effect of sulindac
      sulfone against mammary carcinogenesis and indicate that this compound may have a
      selective effect against carcinogenesis involving alterations in the signal
      transduction cascade of which Ha-ras is a component. Evidence is consistent with
      the involvement of apoptosis in the cancer-inhibitory activity observed.

PMID- 9000567
TI  - Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane
      that induces phase 2 drug-metabolizing enzymes.
AB  - Chemoprevention involves the use of natural or synthetic substances to reduce the
      risk of developing cancer. Two dietary components capable of mediating
      chemopreventive activity in animal models by modulation of drug-metabolizing
      enzymes are sulforaphane, an aliphatic isothiocyanate, and brassinin, an indole
      based dithiocarbamate, both found in cruciferous vegetables. We currently report
      the synthesis and activity of a novel cancer chemopreventive agent, (+/-)-4
      methylsulfinyl-1-(S-methyldithiocarbamyl)-butane (trivial name, sulforamate), an
      aliphatic analogue of brassinin with structural similarities to sulforaphane.
      This compound was shown to be a monofunctional inducer of NAD(P)H:quinone
      oxidoreductase [quinone reductase (QR)], a Phase II enzyme, in murine Hepa 1c1c7
      cell culture and two mutants thereof. Induction potential was comparable to that
      observed with sulforaphane (concentration required to double the specific
      activity of QR, approximately 0.2 microM), but cytotoxicity was reduced by about
      3-fold (IC50 approximately 30 microm). In addition, sulforaphane, as well as the
      analogue, increased glutathione levels about 2-fold in cultured Hepa 1c1c7 cells.
      Induction of QR was regulated at the transcriptional level. Using Northern
      blotting techniques, time- and dose-dependent induction of QR mRNA levels were
      demonstrated in Hepa 1c1c7 cell culture. To further investigate the mechanism of
      induction, HepG2 human hepatoma cells were transiently transfected with QR
      chloramphenicol acetyltransferase plasmid constructs containing various portions
      of the 5'-region of the QR gene. Sulforaphane and the analogue significantly
      induced (P < 0.0001) CAT activity at a concentration of 12.5 microM by
      interaction with the antioxidant responsive element (5-14-fold induction) without
      interacting with the xenobiotic responsive element. Moreover, both compounds
      significantly induced mouse mammary QR and glutathione S-transferase activity
      (feeding of 3 mg/mouse intragastric for 4 days), whereas the elevation of hepatic
      enzyme activities was less pronounced. Both sulforaphane and the analogue were
      identified as potent inhibitors of preneoplastic lesion formation in carcinogen
      treated mouse mammary glands in organ culture (84 and 78% inhibition at 1 microm,
      respectively). On the basis of these results, the sulforaphane analogue can be
      regarded as a readily available promising new cancer chemopreventive agent.

PMID- 9000568
TI  - Preclinical antitumor activity of 6-hydroxymethylacylfulvene, a semisynthetic
      derivative of the mushroom toxin illudin S.
AB  - 6-Hydroxymethylacylfulvene (HMAF; MGI 114) is a novel semisynthetic antitumor
      agent derived from the sesquiterpene mushroom toxin illudin S. In vitro
      cytotoxicity determinations produced IC50 concentrations (concentrations required
      for 50% inhibition of growth) ranging from 160 nM in sensitive MCF-7 human
      mammary carcinoma cells to 17 microM in relatively insensitive murine B16
      melanoma cells. In vivo antitumor activity was consistent with in vitro
      sensitivity. HMAF was very effective in human tumor xenograft models, including
      MX-1 breast carcinoma, MV522 lung adenocarcinoma, and HT-29 colon carcinoma, but
      not murine B16 melanoma or P388 leukemia. Excellent responses were observed in
      animals bearing MX-1 tumors administered i.v. or i.p. doses of 3-7.5 mg/kg daily
      for 5 days, with complete regression recorded in 29 of 30 animals administered
      i.v. HMAF. Extensive tumor shrinkage was also observed with MV522, and
      significant tumor growth inhibition was obtained with HT-29 when animals received
      5 daily i.p. doses ranging from 3.75 to 7.5 mg/kg. Complete regressions were also
      observed in individual animals with MV522 and HT-29. The excellent activity of
      HMAF in several human solid tumor xenografts, including the more refractory MV522
      and HT-29 models, warrants the further investigation of this novel agent in
      clinical trials.

PMID- 9000569
TI  - Preclinical prediction of factors influencing the elimination of 5,6
      dimethylxanthenone-4-acetic acid, a new anticancer drug.
AB  - The glucuronidation of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a newly
      developed anticancer drug, was investigated in vitro to determine factors likely
      to affect the elimination of this compound in patients. Human liver microsomal
      DMXAA glucuronidation followed Michaelis-Menten kinetics, with a mean apparent Km
      of approximately 100 microM. Two cDNA-expressed UGT isoforms, UGT1*02 and UGT2B7,
      had the capacity to glucuronidate DMXAA, although comparative kinetic and
      inhibitor studies were more consistent with a greater contribution of UGT2B7 to
      the human hepatic reaction. Microsomal DMXAA glucuronide formation was screened
      for inhibition by drugs known to be eliminated by glucuronidation. Of the drugs
      screened, significant inhibition was observed with diclofenac, epirubicin,
      indomethacin, R,S-ketoprofen, lorazepam, S-naproxen, oxazepam, and temazepam;
      apparent Ki values ranged from 9.5-318 microM. These values are substantially
      above unbound concentrations of the individual drugs achieved in vivo. DMXAA
      glucuronide was found to be unstable at physiological pH values, and the rate of
      degradation was marginally increased in the presence of albumin. Taken together,
      these data indicate that the kinetics of DMXAA glucuronidation in vivo are likely
      to be linear and unaffected by the coadministration of most glucuronidated drugs,
      but plasma DMXAA clearance may be decreased in patients with renal dysfunction.
      This study illustrates the utility of in vitro techniques for the prediction of
      potential drug interactions and other dispositional characteristics of newly
      developed anticancer drugs before their administration to patients.

PMID- 9000570
TI  - Inhibition of protein synthesis in small cell lung cancer cells induced by the
      diphtheria toxin-related fusion protein DAB389 GRP.
AB  - DAB389 GRP is composed of the catalytic and transmembrane domains of diphtheria
      toxin fused to gastrin-releasing peptide (GRP). DAB389 GRP is selectively
      targeted to, and inhibits protein synthesis in, cell lines expressing GRP
      receptors. Protein synthesis in 5'ET4 cells (BALB/3T3 fibroblasts transfected
      with the gene encoding the GRP receptor) was inhibited by 50% in the presence of
      20 pM DAB389 GRP (IC50, 20 pM). DAB389 GRP did not inhibit protein synthesis in
      untransfected BALB/3T3 cells. A second neuropeptide-conjugated toxin, DAB389 SP,
      directed to cells expressing substance P receptors, was not cytotoxic to 5'ET4
      cells, nor was DAB389 GRP cytotoxic to substance P receptor-bearing cells. DAB389
      GRP cytotoxic effects were receptor specific and were inhibited either by excess
      GRP or anti-GRP antibody. Cytotoxicity was mediated by passage through an acidic
      vesicle, because addition of 10 microM chloroquine to the reaction inhibited
      cytotoxicity. DAB389 GRP and DAB389 SP were tested on a number of tumor cell
      lines. DAB389 GRP inhibited protein synthesis in AR42J rat pancreatic acinar
      cells and HuTu 80 human duodenal adenocarcinoma cells with IC50s of 65 and 200
      pM, respectively. DAB389 SP had an IC50 of 9.5 pM for the AR42J cells and 12 nM
      for the HuTu 80 cell line. A number of small cell lung cancer cell (SCLC) lines
      were tested, and the IC50 for DAB389 GRP ranged from 1.1 to 85 nM. Sensitivity to
      DAB389 GRP appeared to be based on receptor number and receptor type (i.e., GRP
      or neuromedin B preferring). SCLC cells were also sensitive to DAB389 SP, with
      IC50s ranging from 2.4 to 11.5 nM. These results suggest that a potential use
      exists for diphtheria-based fusion toxins as therapeutic agents for treatment of
      SCLC and other neuropeptide receptor-bearing cancers.

PMID- 9000572
TI  - BAT-26, an indicator of the replication error phenotype in colorectal cancers and
      cell lines.
AB  - Instability of microsatellites is a hallmark of the DNA replication error
      phenotype (RER+) due to the inactivation of mismatch repair genes. In humans,
      microsatellite instability has first been described in colorectal tumors
      developing in either hereditary nonpolyposis colorectal cancer or sporadic
      patients. Colorectal tumorigenesis in RER+ and RER- tumors is probably due to
      distinct mechanisms, and RER+ tumors have a better prognosis than RER- tumors.
      The study of the RER status of a tumor may thus be important in the future to
      determine biological prognosis factors and investigate therapeutical strategies.
      The RER status of 134 primary tumors and 26 cell lines derived from colorectal
      cancers was established by PCR amplification and analysis of a minimum of 32
      microsatellite loci. This characterization allowed us to unambiguously classify
      35 primary tumors and 7 cell lines as RER+. Typing of a single poly(A) tract, BAT
      26, was sufficient to confirm the RER status of 159 of these 160 tumors and cell
      lines. Moreover, in DNA from unaffected individuals, normal tissues of a subset
      of the RER+ patients, and all RER- tumors or cell lines, BAT-26 was quasi
      monomorphic, showing only minor size variations. BAT-26 alleles showing
      shortening from 4 to 15 bp were observed in all but 1 of the RER+ tumors and cell
      lines. The size difference between the range of normal large alleles and unstable
      small alleles was sufficient to be detected by electrophoresis on conventional
      polyacrylamide gels stained with ethidium bromide. We thus propose a simple, low
      cost, and rapid method to screen for the RER status of colorectal cancer primary
      tumors and cell lines, even in the absence of matching normal DNA and, in most
      cases, without the need for radioactivity. This method could easily be set up in
      routine laboratories.

PMID- 9000571
TI  - Prognostic utility of serum alpha-N-acetylgalactosaminidase and immunosuppression
      resulted from deglycosylation of serum Gc protein in oral cancer patients.
AB  - Vitamin D3-binding protein (Gc protein), a serum glycoprotein, is the precursor
      for the macrophage activating factor. Cancer patient sera contain alpha-N
      acetylgalactosaminidase that deglycosylates Gc protein. Deglycosylated Gc protein
      cannot be converted to macrophage activating factor, leading to
      immunosuppression. Of 46 oral cancer patients with squamous cell carcinoma,
      approximately 22% had greatly reduced precursor activities. The precursor
      activity of approximately 61% of these patients was moderately reduced. The
      remaining patients (17%) had precursor activities equivalent to those of healthy
      humans. Patients with low precursor activity of serum Gc protein had high serum
      alpha-N-acetylgalactosaminidase activity. In contrast, patients with high
      precursor activity had low serum alpha-N-acetylgalactosaminidase activity. Thus,
      levels of serum alpha-N-acetylgalactosaminidase of individual patients have an
      inverse correlation with precursor activities of their serum Gc protein. Surgical
      removal of tumors resulted in a subtle decrease in serum alpha-N
      acetylgalactosaminidase activity with concomitant increase in the precursor
      activity of serum Gc protein. Serum enzyme analysis of nude mice transplanted
      with a human oral squamous carcinoma cell line revealed that serum alpha-N
      acetylgalactosaminidase activity is directly proportional to tumor burden. Thus,
      alpha-N-acetylgalactosaminidase activity in patient bloodstream can serve as a
      diagnostic/prognostic index.

PMID- 9000573
TI  - The relationship between TP53 mutations and overexpression of p53 and prognosis
      in malignant gliomas of childhood.
AB  - The prognosis for children with high-grade gliomas remains somewhat
      unpredictable. Although prolonged disease control is sometimes achieved after
      surgery, radiotherapy, and chemotherapy, most patients exhibit rapid disease
      progression. Because p53-dependent apoptosis mechanisms are involved in the
      cytotoxic effects of irradiation and chemotherapy, we questioned whether p53
      status might be associated with outcome in childhood malignant gliomas.
      Therefore, we examined p53 status, both immunohistochemically and by direct
      sequencing of exons 5-8, in a series of 29 archival pediatric malignant non
      brainstem gliomas treated consecutively at our institution between 1975 and 1992.
      Eighteen tumors had dense p53 staining in the majority of cells, although only 11
      had mutations of the p53 gene (TP53). On univariate analysis, there was a
      significant association between p53 overexpression and a shorter progression-free
      survival (PFS) and overall survival (OS; P = 0.019 and 0.013, respectively; rank
      sum test). In addition, there was a significant association between TP53
      mutations and a poorer PFS (P = 0.04), and a strong trend toward a shorter OS
      among patients with TP53 mutations (P = 0.06). Median PFS and OS for patients
      with TP53-mutated tumors were 6 months and 16 months, respectively, and for those
      with p53 overexpression 5.5 months and 14 months, respectively, versus 16 months
      and 25 months, respectively, for those without TP53 mutations and 25 months and
      >4 years, respectively, for those without p53 overexpression. The percentage of
      patients in this series with TP53 mutations (37.9%) was substantially higher than
      in previous studies of childhood gliomas and comparable to the frequency of
      mutations noted in adult gliomas. However, both TP53 mutation and p53
      overexpression were significantly less frequent in tumors from children younger
      than 4 than from older children (P = 0.02 and 0.01, respectively). These results
      indicate that p53 mutation and expression status may be associated with prognosis
      in childhood malignant gliomas, and thus may provide a basis for stratifying
      patients biologically in future malignant glioma studies.

PMID- 9000574
TI  - Mutation analysis of glial cell line-derived neurotrophic factor (GDNF), a ligand
      for the RET/GDNF receptor alpha complex, in sporadic phaeochromocytomas.
AB  - Phaeochromocytomas usually occur sporadically but may also be a feature of three
      autosomal dominantly inherited cancer syndromes, multiple endocrine neoplasia
      type 2, von Hippel-Lindau disease (VHL), and, very rarely, type 1
      neurofibromatosis. Germ-line missense mutations in the RET proto-oncogene, which
      encodes a receptor tyrosine kinase, cause multiple endocrine neoplasia type 2. In
      VHL, germ-line mutations in one of the three exons of the VHL tumor suppressor
      gene have been found in the majority of families. Whereas somatic mutations in
      the VHL gene have been common in sporadic renal cell carcinoma, a component
      cancer of VHL, somatic mutations in the RET and VHL genes together have been
      found in approximately 10% of sporadic phaeochromocytomas. Hence, other genes
      must also contribute to the pathogenesis of sporadic phaeochromocytomas. Recent
      data have suggested that glial cell line-derived neurotrophic factor (GDNF) is a
      ligand for RET and acts via a heterotetrameric receptor complex that includes
      GDNF receptor alpha, which provides ligand binding capabilities, and RET, which
      provides the signaling component. Thus, both GDNF and GDNFR-alpha are plausible
      candidate genes for involvement in the pathogenesis of phaeochromocytomas. To
      investigate the role of GDNF in sporadic phaeochromocytomas, we scanned a panel
      of 22 tumors. Among these samples, only a conservative sequence variant was
      detected in exon 2 of GDNF. No disease-associated somatic GDNF mutations or gross
      gene amplification were detected in these tumors, suggesting only a minor role
      for GDNF in the genesis of phaeochromocytomas.

PMID- 9000575
TI  - Androgen receptor gene amplification: a possible molecular mechanism for androgen
      deprivation therapy failure in prostate cancer.
AB  - Progression of prostate cancer during endocrine therapy is a major clinical
      problem, the molecular mechanisms of which remain poorly understood.
      Amplification of the androgen receptor (AR) gene was recently described in
      recurrent prostate carcinomas from patients who had failed androgen deprivation
      therapy. To evaluate the hypothesis that amplification of the AR gene is a cause
      for the failure of androgen deprivation therapy in prostate cancer, we studied
      whether AR amplification leads to gene overexpression, whether the amplified AR
      gene is structurally intact, and whether tumors with AR amplification have
      distinct biological and clinical characteristics. Tumor specimens were collected
      from 54 prostate cancer patients at the time of a local recurrence following
      therapy failure. In 26 cases, paired primary tumor specimens from the same
      patients prior to therapy were also available. Fifteen (28%) of the recurrent
      therapy-resistant tumors, but none of the untreated primary tumors, contained AR
      gene amplification as determined by fluorescence in situ hybridization. According
      to single-stranded conformation polymorphism analysis, the AR gene was wild type
      in all but one of the 13 AR amplified cases studied. In one tumor, a presumed
      mutation in the hormone-binding domain at codon 674 leading to a Gly --> Ala
      substitution was found, but functional studies indicated that this mutation did
      not change the transactivational properties of the receptor. AR amplification was
      associated with a substantially increased level of mRNA expression of the gene by
      in situ hybridization. Clinicopathological correlations indicated that AR
      amplification was most likely to occur in tumors that had initially responded
      well to endocrine therapy and whose response duration was more than 12 months.
      Tumors that recurred earlier or those that showed no initial therapy response did
      not contain AR amplification. The median survival time after recurrence was two
      times longer for patients with AR amplification in comparison to those with no
      amplification (P = 0.03, Willcoxon-Breslow test). In conclusion, failure of
      conventional androgen deprivation therapy in prostate cancer may be caused by a
      clonal expansion of tumor cells that are able to continue androgen-dependent
      growth despite of the low concentrations of serum androgens. Amplification and
      the increased expression of a wild-type AR gene may play a key role in this
      process.

PMID- 9000576
TI  - Defects in p21WAF1/CIP1, Rb, and c-myc signaling in phorbol ester-resistant
      cancer cells.
AB  - Growth arrest and differentiation of leukemic cells by phorbol 12-myristate 13
      acetate (PMA) is accompanied by p53-independent activation of p21WAF1/CIP1 and c
      myc down-regulation. We show that despite p21 induction in 7 of 12 human cancer
      cell lines treated with PMA, growth inhibition was observed only in two cell
      lines (SKBr3 breast and LNCaP prostate cancer cells). Treatment of SKBr3 and
      LNCaP cells with PMA was followed by Raf-1 hyperphosphorylation, p21 induction,
      Rb hypophosphorylation, c-myc down-regulation and growth inhibition. The 10
      remaining PMA-resistant cell lines were comprised of 5 that failed to induce p21
      and 5 that induced p21 but had defects in steps putatively downstream of this (Rb
      hypophosphorylation and c-myc down-regulation). Exogenous expression and
      subsequent failure to down-regulate c-myc protein expression in SKBr3 and LNCaP
      cells was correlated with acquisition of resistance to the growth inhibitory
      effect of PMA. Exogenous p21 expression down-regulated c-myc protein in PMA
      sensitive cancer cells. Our findings suggest that induction of p21 and down
      regulation of c-myc may be necessary steps in a PMA-induced growth-inhibitory
      pathway in cancer cells.

PMID- 9000577
TI  - Telomerase activity is detected in pancreatic cancer but not in benign tumors.
AB  - Activation of telomerase and stabilization of telomeres are considered to be
      necessary for immortalization of human tumor cells. In the present study,
      telomerase activity was detected in 41 (95%) of 43 pancreatic cancer specimens
      but was detectable in none of 11 benign pancreatic tumors and only one of 3
      pancreatitis samples. Low levels of telomerase activity were detected in 5 (14%)
      of 36 adjacent "normal" pancreatic tissues. These five telomerase-positive
      "normal" specimens were obtained from patients that also had pancreatic cancer
      and may reflect occult microinvasion. Telomerase activity was examined in 12 ex
      vivo brushing samples of the pancreatic duct, and 8 of 8 with pancreatic cancer
      had detectable telomerase activity, whereas 0 of 4 of benign lesions (cystadenoma
      and pancreatitis) did. These findings suggest that telomerase activity in cells
      derived from pancreatic ducts may be useful in the diagnosis of cancer and that
      telomerase activity may be a critical or rate-limiting step in pancreatic
      carcinogenesis.

PMID- 9000578
TI  - Reduction of metastatic properties of BL6 melanoma cells expressing terminal
      fucose(alpha)1-2-galactose after alpha1,2-fucosyltransferase cDNA transfection.
AB  - We reported previously that transfection of BL6 melanoma cells that do not
      express the alpha1,3-galactosyltransferase (alpha1,3GT) gene with the alpha1,3GT
      cDNA resulted in synthesis and expression of alpha-galactosyl epitopes
      (Gal(alpha)1-3Gal(beta)1-4GlcNAc-R) and an impairment of their metastatic
      potentials. It was of interest to test whether inhibition of metastatic
      properties of BL6 melanoma cells is specifically associated with the appearance
      of the terminal alpha-Gal or whether capping N-acetyllactosamine with another
      oligosaccharide would also affect the metastatic properties of BL6 melanoma
      cells. For this purpose, BL6-2 clone isolated from B16BL6 melanoma was
      transfected with the alpha1,2-fucosyltransferase (alpha1,2FT) cDNA. The
      alpha1,2FT catalyzes a transglycosylation reaction, resulting in syntheses of the
      Fuc(alpha)1-2Gal(beta)1-4GlcNAc-R structure, which is known as the H antigen of O
      blood group in humans and is also synthesized in some cells of mice. Transfection
      of BL6 melanoma cells with the alpha1,2FT cDNA resulted in the appearance of the
      terminal Fuc(alpha)1-2Gal(beta)1-4GlcNAc-R epitopes reacting with the Ulex
      europaeus agglutinin lectin. In parallel, the transfected cells showed a decrease
      in N-acetyllactosamine sialylation. Decline in sialylation of the transfected
      cells is likely to be the result of competition between alphal,2FT and alpha2,3-
      or alpha2,6-sialyltransferases for the common substrate N-acetyllactosamine
      (Gal(beta)1-4GlcNAc-R) on N-linked carbohydrate chains of glycoproteins and
      glycolipids. The alpha1,2FT-transfected BL6-2 cells showed an increase in
      homotypic aggregation. In parallel, metastatic ability of the alpha1,2FT
      transfected BL6-2 cells was reduced significantly in the immunocompetent as well
      as immunosuppressed (X-irradiated) mice. Thus, these data imply that capping N
      acetyllactosamine with alphaGal or alphaFuc and the corresponding reduction in
      sialylation of BL6-2 melanoma cells were associated with reduction of their
      metastatic potential.

PMID- 9000579
TI  - Transforming function of the HOX11/TCL3 homeobox gene.
AB  - The HOX11/TCL3 homeobox gene was identified at the breakpoint region in pediatric
      T-cell acute lymphoblastic leukemia harboring 10q24 chromosomal translocations.
      We previously reported that primary murine bone marrow cells transduced ex vivo
      with a recombinant HOX11-containing retrovirus, MSCV-HOX11, gave rise to cell
      lines at high frequency having characteristics of early myeloid cells. Cell lines
      were also established from the bone marrow and spleen of transplant recipients
      sacrificed 5 months after engraftment with MSCV-HOX11-transduced bone marrow
      cells. These latter lines, which exhibited a more differentiated myelomonocytic
      phenotype, harbored proviruses encoding a smaller HOX11 protein. None of the mice
      that received HOX11-expressing bone marrow cells or myeloid cell lines developed
      leukemia during 6-month observation periods. Here, we report that two bone marrow
      transplant recipients eventually developed T-cell acute lymphoblastic leukemia
      like malignancies at 7 and 12 months posttransplant, indicating that progression
      to a fully malignant state required additional mutations. One tumor synthesized
      full-length HOX11 whereas the other expressed the smaller version of the protein.
      The smaller HOX11 protein suffered a carboxyl-terminal truncation. We
      subsequently constructed MSCV-based retroviral vectors expressing deleted forms
      of HOX11 and identified an amino-terminal region that was dispensible for
      generation of myeloid cell lines having a similar phenotype as those induced by
      full-length HOX11. We thus conclude that regions near the amino and carboxyl
      termini of HOX11 are not essential for transforming function, nor do they appear
      to determine the lineage or stage of differentiation of the target cell for
      transformation.

PMID- 9000580
TI  - Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death
      (necrosis).
AB  - The term cell necrobiology is introduced to comprise the life processes
      associated with morphological, biochemical, and molecular changes which
      predispose, precede, and accompany cell death, as well as the consequences and
      tissue response to cell death. Two alternative modes of cell death can be
      distinguished, apoptosis and accidental cell death, generally defined as
      necrosis. The wide interest in necrobiology in many disciplines stems from the
      realization that apoptosis, whether it occurs physiologically or as a
      manifestation of a pathological state, is an active mode of cell death and a
      subject of complex regulatory processes. A possibility exists, therefore, to
      interact with the regulatory machinery and thereby modulate the cell's propensity
      to die in response to intrinsic or exogenous signals. Flow cytometry appears to
      be the methodology of choice to study various aspects of necrobiology. It offers
      all the advantages of rapid, multiparameter analysis of large populations of
      individual cells to investigate the biological processes associated with cell
      death. Numerous methods have been developed to identify apoptotic and necrotic
      cells and are widely used in various disciplines, in particular in oncology and
      immunology. The methods based on changes in cell morphology, plasma membrane
      structure and transport function, function of cell organelles, DNA stability to
      denaturation, and endonucleolytic DNA degradation are reviewed and their
      applicability in the research laboratory and in the clinical setting is
      discussed. Improper use of flow cytometry in analysis of cell death and in data
      interpretation also is discussed. The most severe errors are due to i)
      misclassification of nuclear fragments and individual apoptotic bodies as single
      apoptotic cells, ii) assumption that the apoptotic index represents the rate of
      cell death, and iii) failure to confirm by microscopy that the cells classified
      by flow cytometry as apoptotic or necrotic do indeed show morphology consistent
      with this classification. It is expected that flow cytometry will be the dominant
      methodology for necrobiology.

PMID- 9000582
TI  - Distribution of estrogen receptor heterogeneity in growing MCF-7 cells measured
      by quantitative microscopy.
AB  - The existence of interactive subpopulations is a biological feature that can
      modulate the proliferation of tumor cells. The hormone-responsive breast cancer
      cell line MCF-7 has been described as heterogeneous in terms of density. In this
      study we describe a quantitative image analysis methodology that we developed for
      the in situ detection of different subpopulations in MCF-7 cell cultures. Using
      this technology, we demonstrate the heterogeneity of the MCF-7 cell line in terms
      of both nuclear size and estrogen-receptor content. Analysis of the organization
      (topography) of the different subpopulations in culture reveals a nonrandom
      distribution of cells. When studying the development of these cell subpopulations
      as a function of time of culture, we observe modifications of their topography
      associated with an increase of estrogen-receptor-expressing cells. Moreover, the
      use of cluster analysis allows study of the local organization of these
      subpopulations. These changes appear to be independent of cell proliferation.

PMID- 9000581
TI  - Quality assurance in DNA image analysis on diploid cells.
AB  - DNA image analysis is presently performed in many laboratories. Before general
      extrapolation of results between different laboratories, validation has to be
      performed for interlaboratory studies on DNA image analysis. The aim of this
      study was to establish the performance of different DNA image analysis
      instruments when measuring different diploid cells. On three separate parts of
      the same object slide, human liver cells, white blood cells, and imprints of a
      breast fibroadenoma were sampled. In this quality assurance interlaboratory
      study, 13 laboratories participated voluntarily. Two slides were sent to each
      participating laboratory: one Feulgen and one unstained to be stained according
      the participating laboratory in-house procedure. The features integrated optical
      density (IOD) and object AREA were recorded for each nucleus. For calculation of
      the results, the average IOD value of liver diploid cells was set at 2c. A
      striking difference was observed between the different presumed diploid cell
      types, from almost 1c to 3c. This variation was not dependent on central or in
      house staining. Although in-house calibration was performed for each image
      analysis system, a surprisingly large variation existed in the reported object
      AREA, irrespective of the cell type. These results clearly demonstrate that
      measurements performed in one laboratory cannot be extrapolated to the outcome of
      others and support the need for standardization. The use of external control
      cells works well for comparison of instruments. In conclusion, in DNA image
      analysis quality control is necessary, standardization is obligatory, and the use
      of an internal control for determination of the diploid peak in a histogram of
      patient samples is recommended.

PMID- 9000583
TI  - Neural net-based identification of cells expressing the p300 tumor-related
      antigen using fluorescence image analysis.
AB  - We report on preliminary investigations of the use of an image analysis system to
      perform preliminary algorithmic classification of images of fluorochrome-labeled
      cells followed by capture of gray-level images of potentially abnormal cells for
      analysis by a neural network. Cells were labeled with an antibody against a
      bladder cancer tumor-associated antigen, and the neural net was used to
      distinguish true-positive cells from negative cells, false-positive cells
      (autofluorescent or nonspecific labeling), and cell-sized artifacts. Gray-level
      cell images were digitized and processed for analysis by a feed-forward neural
      network using back-propagation. The network was trained and tested with two
      independent image sets. Various network configurations and activation functions
      were investigated, including a sinusoidal activation function. At high power, the
      network agreed completely with the human observer's classification. At low power,
      a strong clustering of cells classified by the network with expert classification
      was seen, while the neural network showed roughly 75% concordance with the human
      observer. In addition, a set of four features extracted from raw cell images were
      investigated. The features were: shape factor, texture, area, and average pixel
      intensity. A network trained with these features performed better than one
      operating with gray-level images. We conclude that using neural networks to
      recognize and classify images captured by an image analysis microscope is
      feasible.

PMID- 9000584
TI  - Flow cytometric analysis and confocal imaging of anticancer
      alkylaminoanthraquinones and their N-oxides in intact human cells using 647-nm
      krypton laser excitation.
AB  - Flow cytometry and laser-scanning confocal fluorescence microscopy have been used
      in the study of the pharmacodynamics, in single intact cells, of two novel
      alkylaminoanthraquinones (AQ4 and AQ6), structurally based upon the mid-red
      excitable but very weakly fluorescent anticancer agent mitoxantrone, together
      with their respective N-oxide derivatives (AQ4NO and AQ6NO). The drug design
      rationale was that N-oxide modifications generates prodrug forms suitable for
      selective bioreductive-activation in hypoxic tumor cells. DNA-binding ranked in
      the order of mitoxantrone > AQ6 > AQ4 > AQ6NO >> AQ4NO. Using both cytometric
      methods a similar ranking was found for whole cell and nuclear location in human
      transformed fibroblasts. However, AQ6 showed enhanced nuclear uptake compared
      with mitoxantrone, in keeping with its greater capacity to inhibit DNA synthesis.
      Partial charge neutralisation by N-oxide derivatization resulted in loss of DNA
      synthesis inhibition but retention of the ability to accumulate in the cytosol,
      an important property for prodrug development. We conclude that both flow
      cytometry and confocal imaging revealed biologically significant differences
      between analogues for subcellular distribution and retention properties. The
      study demonstrates the potential for these complementary 647-nm krypton laser
      line-based fluorometric methods to provide relevant structure-activity
      information in anthraquinone drug-design programmes.

PMID- 9000585
TI  - Cell cycle changes associated with formation of Pt-DNA adducts in human ovarian
      carcinoma cells with different cisplatin sensitivity.
AB  - The possible correlation between alterations in cytokinetic response to cisplatin
      (CP) treatment and drug resistance in human ovarian carcinoma cell lines was
      examined. Using dual parameter flow cytometry, we performed detailed time-course
      and dose-response analysis of cell cycle modifications in the parental A2780 and
      resistant A2780/CP cells exposed to CP. The data suggested that drug treatment
      resulted in similar types of cell cycle alterations in cells with different CP
      sensitivity. Rapid normalization of the cytokinetic pattern in both cell lines at
      low doses of CP was observed. At higher drug concentrations reversible S phase
      delay predominated, accompanied by blocks in both G1/S and G2/M and followed by
      complete normalization of cytokinetic patterns in the surviving cells. CP
      treatment by lethal doses resulted in almost complete S phase block. The
      surviving cells at 72 h accumulated in G2 phase. CP-induced cell cycle
      perturbations, among which the most pronounced were alterations in the S phase
      populations, correlated with the level of DNA damage, but not with cell survival
      in these cell lines. However, at identical levels of DNA damage, the resistant
      A2780/CP cell line demonstrated decreased p53 induction and decreased apoptosis
      compared to the parental cell line. Thus, at equivalent levels of DNA damage,
      resistance in this model system correlated with a diminished p53-dependent
      apoptotic pathway rather than with differences in cell cycle response.

PMID- 9000586
TI  - Rare-event sorting by fixed-time flow cytometry based on changes in intracellular
      free calcium.
AB  - Neurotransmitter induced intracellular free calcium, [Ca2+]i , increases were
      used to sort rare responding cells by fixed-time flow cytometry. Non-transfected
      and transfected NIH/3T3 mouse fibroblasts were stimulated with a cocktail of the
      neurotransmitters oxytocin, serotonin, substance P, noradrenalin, vasopressin,
      and neurotensin. In both cultures no detectable response to this cocktail was
      found. Non-transfected cells were stimulated with the cocktail and sorted for
      rare responders. After two subsequent aseptic sorts, each followed by subsequent
      cultivation, cell cultures with more than 60% serotonin responsive cells were
      obtained. The initial frequency of these responders was less than 3 x 10(-4).
      NIH/3T3 cells transfected with total genomic DNA from the rat pituitary-gland
      cell line GH3 were sorted with a cocktail without serotonin. After two sorts and
      subsequent cloning two clones were obtained. Each of these clones was sensitive
      to one component of the cocktail (oxytocin or substance P). The initial frequency
      of one responder type was estimated to be less than 2 x 10(-5). These results
      demonstrate that sorting by fixed-time flow cytometry is a sensitive tool to
      enrich very rare cells from heterogeneous cultures.

PMID- 9000588
TI  - Quantitative cytometry of MHC class I digestion from living cells.
AB  - Digestion of crude membrane preparations with papain releases the extracellular
      portion of major histocompatibility complex (MHC) class I molecules. MHC class I
      molecules are integral membrane glycoprotein complexes formed by the noncovalent
      association of 2 invariant molecules, the heavy chain and the beta2-microglobulin
      (beta2-m), to a wide array of peptides. The cleaved soluble moiety retains the
      antigenic properties of the intact membrane-bound complex. Here we show that MHC
      class I digestion may be carried out on living cells, and we quantitate the
      surface expression of MHC complexes by a combined cytometric/high performance
      liquid chromatographic (HPLC) approach. Papain digestion results in time- and
      dose-dependent disappearance of membrane MHC-associated-fluorescence as detected
      by FACS analysis with MHC-specific monoclonal antibodies (mAbs). beta2-m and
      peptides became detectable by HPLC analysis and western blotting in the digestion
      buffer and were quantitated by comparison with purified standards. The cytometric
      assessment of the digestion allows one to simultaneously monitor efficacy and
      toxicity of the treatment. The procedure we describe allows to selectively
      retrieve by affinity chromatography MHC from the cell membrane, avoiding any
      contamination due to intracellular, "immature" MHC molecules.

PMID- 9000587
TI  - Flow cytometric analysis of activation markers on stimulated T cells and their
      correlation with cell proliferation.
AB  - The expression of activation antigens, namely CD25, CD69, CD71, and HLA-DR on T
      cells from 15 healthy individuals stimulated with different mitogens and specific
      antigens was evaluated by immunofluorescence assay and flow cytometric analysis
      and compared with cell proliferation as a function of [3H]thymidine
      incorporation. CD69 was the earliest expressed antigen on stimulated cells, while
      HLA-DR was the latest. Regardless of the stimulus used, lymphocytes expressing
      CD25 and CD71 were always more numerous than cells expressing CD69 and HLA-DR.
      Variations in the proportion of CD4+ and CD8+ T cells expressing each activation
      marker were observed with different antigenic stimuli. The expression of each
      activation marker showed overall agreement with the [3H]thymidine incorporation
      assay in discriminating between positive and negative immune response. However,
      no correlation was observed between the percentage of CD25-, CD69-, CD71-, and
      HLA-DR-positive T cells and the amount of [3H]thymidine incorporation. Moreover,
      low doses of mitogens and antigens as well as short time of stimulation were
      sufficient to induce T cells to express activation antigens but not to
      proliferate. Our data show that results obtained by flow cytometry and
      [3H]thymidine incorporation may differ qualitatively, at least under certain
      conditions; this suggests that the 2 assays are complementary, and when combined,
      may gives a clearer understanding of events leading to efficient cell-mediated
      immune response.

PMID- 9000589
TI  - Flow cytometric assessment of hydroxypyridinone iron chelators on in vitro growth
      of drug-resistant malaria.
AB  - The resurgence of drug-resistant malaria makes urgent the evaluation of new
      antimalarial agents. This study describes a flow cytometric method (FCM) for
      testing in vitro drug susceptibility of Plasmodium falciparum malaria to several
      orally active hydroxypyridinone (CP) iron chelators and to the parenteral iron
      chelator desferrioxamine (DF). After exposure of parasites to various
      concentrations of iron chelating agents, aliquots of cultures were fixed with
      glutaraldehyde. The fixed samples were washed and stained for parasite DNA with
      propidium iodide and analyzed by flow cytometry. The remaining cells were pulsed
      with 3H-hypoxanthine, using the microdilution radioisotope method. Both CP and DF
      showed dose-dependent inhibition of parasite growth. Of the compounds studied, DF
      exerted a stronger inhibitory effect. Fifty percent of inhibitory concentrations
      (IC50) of CP and DF determined by DNA fluorescence profiles in the flow cytometer
      were consistent with those obtained from the radioisotope method and by
      microscopic examination. Moreover, the minimum inhibitory concentrations (MIC) of
      drug required to inhibit parasite growth, as detected by the decreasing DNA
      fluorescence intensity of the schizont, correlated with observed abnormal
      microscopic morphology. The validity of the MIC, as indicated by decreased
      fluorescence intensity, was confirmed by subsequent parasite culture. Our FCM
      study demonstrated the sensitivity of both chloroquine- and pyrimethamine
      resistant malaria parasites to iron chelators. Addition of equimolar
      concentrations of ferric ion completely abolished the inhibitory effect of iron
      chelators, indicating the importance of iron for parasite growth and the primary
      effect of the compounds as iron (III) chelating agents. These data demonstrate
      that FCM provides a simple and reliable means for antimalarial drug
      susceptibility testing, and suggest that iron chelators have potential for the
      treatment of drug-resistant malaria.

PMID- 9000590
TI  - Accessibility of 7-aminoactinomycin D to lymphocyte nuclei after paraformaldehyde
      fixation.
AB  - DNA-protein interactions, mainly DNA-histone interactions, are thought to play an
      essential role in the packing mechanisms of chromatin as well as in
      transcriptional control. In this context it is important to develop new methods
      to study DNA-protein interactions and structural changes associated with them.
      Paraformaldehyde (PFA) has been shown to crosslink proteins, mainly histones, to
      DNA; and in this short study we have used a system with the DNA-binding dye 7
      aminoactinomycin D (7-AAMD) as an indirect probe for PFA fixation. The aim was to
      investigate the dynamics of fixation on the binding of this dye to intact human
      lymphocytes. The results show a decrease in accessibility of 7-AAMD,initially
      affecting both the nonspecific binding of 7-AAMD and the high affinity binding
      sites, and thereafter mainly the high affinity binding sites. We conclude that
      fixation with PFA is a long-term reaction that requires a fixation time of
      several hours at a sufficient concentration to be completed. Our findings suggest
      that staining with a low concentration of 7-AAMD after extensive PFA fixation may
      be used to obtain information on DNA-protein interactions in intact cells.

PMID- 9000591
TI  - Infrequent methylation of CDKN2A(MTS1/p16) and rare mutation of both CDKN2A and
      CDKN2B(MTS2/p15) in primary astrocytic tumours.
AB  - In a series of 46 glioblastomas, 16 anaplastic astrocytomas and eight
      astrocytomas, all tumours retaining one or both alleles of CDKN2A (48 tumours)
      and CDKN2B (49 tumours) were subjected to sequence analysis (entire coding region
      and splice acceptor and donor sites). One glioblastoma with hemizygous deletion
      of CDKN2A showed a missense mutation in exon 2 (codon 83) that would result in
      the substitution of tyrosine for histidine in the protein. None of the tumours
      retaining alleles of CDKN2B showed mutations of this gene. Glioblastomas with
      retention of both alleles of CDKN2A (14 tumours) and CDKN2B (16 tumours)
      expressed transcripts for these genes. In contrast, 7/13 glioblastomas with
      hemizygous deletions of CDKN2A and 8/11 glioblastomas with hemizygous deletions
      of CDKN2B showed no or weak expression. Anaplastic astrocytomas and astrocytomas
      showed a considerable variation in the expression of both genes, regardless of
      whether they retained one or two copies of the genes. The methylation status of
      the 5' CpG island of the CDKN2A gene was studied in all 15 tumours retaining only
      one allele of CDKN2A as well as in the six tumours showing no significant
      expression of transcript despite their retaining both CDKN2A alleles. Three
      tumours (one of each malignancy grade studied) were found to have partially
      methylated the 5' CpG island of CDKN2A. It appears that in human astrocytic
      gliomas point mutations of the CDKN2A and CDKN2B genes are uncommon and
      hypermethylation of the 5' CpG region of CDKN2A does not appear to be a major
      mechanism for inhibiting transcription of this gene.

PMID- 9000592
TI  - Heparin oligosaccharides: inhibitors of the biological activity of bFGF on Caco-2
      cells.
AB  - A number of growth factors, including members of the fibroblast growth factor
      (FGF) family - hepatocyte growth factor, vascular endothelial growth factor and
      heparin-binding epidermal growth factor - are dependent on heparan sulphate (HS)
      for biological activity mediated through their high-affinity signal-transducing
      receptors. This obligate requirement for HS prompted the search for antagonists
      of HS function that could be used as anti-growth factor drugs for the treatment
      of cancer. Basic FGF (bFGF) was the focus of this study. Caco-2, a human colon
      carcinoma cell line, was adapted to growth in serum-free medium so that
      investigation of its growth factor requirements for growth and migration could be
      performed in defined conditions (Jayson GC, Evans GS, Pemberton PW, Lobley RW,
      Allen T 1994, Cancer Res, 54, 5718-5723). This cell line multiplied and moved in
      a dose-dependent manner in response to bFGF. Here, we show that the mitogenic
      response to bFGF is dependent on the presence of heparan sulphate. A library of
      heparin oligosaccharides with uniform composition but variable length was
      generated [general formula [IdoA(2S)-GlcNS(6S)n], and oligosaccharides of defined
      lengths were tested for their ability to inhibit the biological activity of bFGF.
      While intact heparin and heparin-derived fragments of 12 monosaccharide units did
      not affect bFGF-induced cell division or bFGF-induced cell migration,
      octasaccharides and decasaccharides potently inhibited the bFGF-induced growth
      and migration responses. In particular, octasaccharides completely inhibited
      these biological activities at 10 microg ml-, a clinically achievable and
      tolerable concentration. This study shows that the length of an oligosaccharide
      determines its ability to block the biological activity of bFGF. The observation
      that the biological activity of cell-surface heparan sulphate can be antagonized
      in this way in a human carcinoma cell line suggests that oligosaccharides should
      be investigated further as anti-growth factor agents for the treatment of cancer.
      In addition, the results suggest that the clinical evaluation of low-molecular
      weight heparin (LMWH) as an anti-cancer agent might benefit from subfractionation
      of the LMWH, to remove oligosaccharides of 12 or more residues.

PMID- 9000593
TI  - Cloning and characterization of a 77-kDa oestrogen receptor isolated from a human
      breast cancer cell line.
AB  - We have cloned and characterized a 77-kDa oestrogen receptor (ER) from an
      oestrogen-independent subclone of the MCF-7 human breast cancer cell line. This
      receptor contains an in-frame, tandem duplication of exons 6 and 7, located in
      the steroid-binding domain of the ER. This mutation has abrogated ligand binding,
      but not DNA binding, in this mutant ER. We previously described the partial
      structure of a unique oestrogen receptor (ER) that is expressed in an oestrogen
      independent MCF-7:2A subclone of the breast cancer cell line MCF-7 (Pink JJ, Wu
      SQ, Wolf DM, Bilimoria MM, Jordan VC 1996a, Nucleic Acids Res 24 962-969).
      Sequence analyses determined the molecular weight of this 80-kDa ER to be 77 kDa,
      and hereafter this protein will be designated as ER77. Examination of the entire
      coding sequence of the ER77 mRNA indicates that it contains a tandem duplication
      of exons 6 and 7. Using a coupled transcription/translation system, a 77-kDa ER,
      which corresponds to the protein observed in the MCF-7:2A cells, was expressed.
      The ER77 protein does not bind the ligands [3H] oestradiol or [3H]tamoxifen
      aziridine. In DNA binding gel shift assays, the in vitro synthesized ER77 binds
      to a consensus vitellogenin A2 oestrogen-response element. In transient
      transfection experiments, the mutant ER, alone or in combination with the wild
      type ER, does not induce expression of an oestrogen-responsive luciferase
      reporter construct. In fact, expression of the ER77 in the ER-positive T47D:A18
      cell line inhibits E2-induced luciferase expression. Overexpression of wild-type
      ER in T47D:A18 cells leads to elevated constitutive expression of the luciferase
      reporter, which was inhibited by co-transfection with ER77. These data suggest
      that the ER77 can interfere with normal ER activity and does not act as a
      constitutive activator of oestrogen-independent growth in MCF-7:2A cells.
      Consequently, the constitutive growth observed in MCF-7:2A cells is probably the
      result of other ER-mediated pathways.

PMID- 9000594
TI  - Fibroblast growth factor 2 in breast cancer: occurrence and prognostic
      significance.
AB  - This paper examines the expression of fibroblast growth factor 2 (FGF-2) in the
      malignant human breast. Semiquantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) was used to assess the level of expression of FGF-2 in a series
      of 51 patients clinically followed up for a median of 84 months (Luqmani et al,
      1992). Immunohistochemistry and Western blotting were used to show that the level
      of FGF-2 in breast tissues correlated with the amount of FGF-2 mRNA. FGF-2 was
      present in both malignant and non-malignant breast, although less was expressed
      in malignant tissues as determined by all three methods. Immunohistochemistry on
      frozen sections of breast tissue showed expression of FGF-2 in myoepithelial and
      epithelial cells in non-malignant samples and generally lower or undetectable
      levels of staining in malignant epithelial cells. The results obtained by
      immunohistochemistry correlated well with RT-PCR data showing similar levels of
      FGF-2 and FGF-2 mRNA expression in samples. No correlation was found between FGF
      2 mRNA expression and T stage, nodal status or oestrogen receptor status.
      However, Kaplan-Meier survival plots show that higher levels of FGF-2 are
      associated with improved overall and disease-free survival. We suggest that FGF-2
      expression may have value as a prognostic indicator in breast cancer.

PMID- 9000595
TI  - Extracellular nucleotides stimulate proliferation in MCF-7 breast cancer cells
      via P2-purinoceptors.
AB  - Nucleotides such as ATP can act as extracellular effector molecules by
      interaction with specific cellular receptors known as P2-purinoceptors. Recently,
      we cloned the human P2U purinoceptor from osteoclastoma and demonstrated its
      expression in skeletal tissues. In the current study we have investigated the
      expression of P2U purinoceptors in human breast tumour cell lines and examined
      functional effects of extracellular nucleotides on these cells. By reverse
      transcription-linked polymerase chain reaction (RT-PCR) the expression of mRNA
      for P2U purinoceptors was demonstrated in four human breast cancer cell lines,
      Hs578T, MCF-7, SK-Br3 and T47-D. In MCF-7 cells, extracellular ATP (1-100 microM)
      elevated intracellular free calcium concentration [Ca2+]i, indicating that these
      cells express functional P2-purinoceptors. UTP elevated [Ca2+]i in an identical
      manner to ATP, whereas 2-methylthioATP was completely ineffective, and ADP only
      partially effective. This pharmacological profile suggests that the P2U subtype
      may be the only P2-purinoceptor expressed by these cells. The functional
      significance of P2U purinoceptor expression by MCF-7 cells was investigated by
      analysing the effects of extracellular ATP on cell proliferation. The slowly
      hydrolysed analogue of ATP, ATPgammaS (which was also shown to elevate [Ca2+]i),
      induced proliferation of MCF-7 cells when added daily to serum-free cultures over
      a period of 3 days. ATPgammaS-induced proliferation was demonstrated by three
      separate methods, detection by scintillation counting of [3H]thymidine
      incorporation, immunocytochemical detection of 5-bromo-2-deoxyuridine
      incorporation and direct counting of cell numbers. These data suggest that ATP,
      possibly released at sites of tissue injury or inflammation, may be capable of
      growth factor action in promotion of tumour proliferation or progression.

PMID- 9000596
TI  - Transplantable rat thyroid cancer cell line FRTC transformed with muramyl
      dipeptide.
AB  - A rat thyroid cancer cell line, FRTC, was established from the normal rat thyroid
      cell line, FRTL-5. FRTL-5 cells were cultured in vitro with N-acetylmuramyl-L
      alanyl-D-isoglutamine (MDP) for 4 days and were transplanted intraperitoneally
      into Fisher rats. Disseminated tumour formation in the peritoneum was found in
      ten out of ten rats in which MDP-treated FRTL-5 cells were transplanted. Colloid
      like structures stained with anti-thyroglobulin (Tg) antibodies were observed in
      the tumours. On the other hand, no tumour was found in any of the rats in which
      untreated FRTL-5 cells were transplanted. No morphological changes were observed
      in FRTL-5 cells after long-term in vitro culture in the presence of MDP. MDP had
      no effect on thymidine incorporation, the production of cAMP or the expression of
      c-myc in FRTL-5 cells in vitro. Cells from the tumour (FRTC) secreted Tg in vitro
      and expressed Tg, thyroid peroxidase (TPO) and thyrotropin (TSH) receptor mRNA.
      The expression of TSH receptor mRNA increased in FRTC cells after TSH
      stimulation. FRTC cells produced cAMP in response to TSH stimulation in a dose
      dependent manner. However, the growth of FRTC cells was TSH independent.
      Expression of c-myc and c-fos was observed in FRTC cells in vivo as well as in
      vitro. FRTC cells formed tumours in Fisher rats when transplanted subcutaneously.
      FRTC cells have several characteristics of differentiated thyroid cancer cells
      and may provide a good model for the study of human differentiated thyroid
      cancers.

PMID- 9000598
TI  - Photodynamic targeting of human retinoblastoma cells using covalent low-density
      lipoprotein conjugates.
AB  - Combination of photosensitizers with carrier molecules has been shown to enhance
      the efficiency of photodynamic therapy (PDT). Owing to an increased expression of
      their receptors on some malignant and proliferating cells, low-density
      lipoproteins (LDLs) are potential endogenous carriers. A photosensitizer, chlorin
      e6 (Ce6), was covalently bound to LDL via carbodiimide activation. The Ce6-LDL
      conjugate was evaluated on a fibroblast cell line with defined LDL receptor
      expression and a retinoblastoma cell line (Y79). Uptake of free Ce6 and Ce6
      either covalently bound to or complexed with LDL was measured by
      spectrofluorimetry. Phototoxicity after irradiation at 660 nm was determined by a
      mitochondrial activity assay (MTT). Covalent binding to LDL significantly
      increased the uptake of Ce6 for both cell lines by a factor of 4-5. A Ce6: LDL
      binding ratio of 50:1 was optimal. A receptor-mediated uptake was demonstrated by
      saturability and competitive inhibition by free LDL. Binding also occurred at 2
      degrees C and was attributed to non-specific associations. Irradiation with 10 J
      cm-2 of 660 nm light after treatment of cells with Ce6-LDL conjugate reduced the
      MTT activity by 80%, while free or mixed Ce6 induced a maximum of 10% reduction
      in the MTT activity following identical treatment conditions. These data suggest
      that targeting of LDL receptor-bearing cells using covalently bound carriers,
      such as LDL, might increase the efficiency and selectivity of PDT. Intraocular
      tumours such as retinoblastomas could be appropriate targets for such an approach
      owing to the ease of access of light sources and the need for non-invasive
      approaches in sensitive ocular sites.

PMID- 9000599
TI  - In vivo detection of ifosfamide by 31P-MRS in rat tumours: increased uptake and
      cytotoxicity induced by carbogen breathing in GH3 prolactinomas.
AB  - The direct detection and monitoring of anti-cancer drugs in vivo by magnetic
      resonance spectroscopy (MRS) may lead to improved anti-cancer strategies. 31P-MRS
      has been used to detect and quantify ifosfamide (IF) in vivo in GH3 prolactinomas
      and N-methyl-N-nitrosourea (MNU)-induced mammary tumours in rats. The average
      concentration of IF in the GH3 prolactinoma over the first 2 h following a dose
      of 250 mg kg-1 i.v. was calculated to be 0.42 micromol g-1 wet weight, with a
      half-life of elimination (t1/2) of 2-4 h. Carbogen (95% oxygen/5% carbon dioxide)
      breathing increased the amount of IF taken up by the GH3 prolactinoma by 50%
      (P<0.01) to 0.68 micromol g-1 wet weight, although t1/2 elimination rates were
      unchanged. IF was also detected in the liver in vivo, with a t1/2 of about 1 h.
      Carbogen breathing did not affect the maximum peak area (Cmax) or the t1/2 in the
      liver. Most importantly, the carbogen-induced increase in IF uptake by the tumour
      caused significant growth delay at all time points in the GH3 tumour growth
      between day 5 and day 12 (P< 0.01) compared with IF alone. These findings show
      that carbogen breathing has potential for increasing the efficacy of anti-cancer
      drugs. Isolated GH3 cells were sensitive to the parent drug (IF) in vitro (IC50 =
      1.3 +/- 0.2 mM) suggesting that the GH3 cells may be either expressing P450
      enzymes or are sensitive to the parent drug per se.

PMID- 9000597
TI  - Involvement of hepatocyte growth factor in increased integrin expression on HepG2
      cells triggered by adhesion to endothelial cells.
AB  - Adhesion of cancer cells to vascular endothelium is an important step in
      haematogenous metastasis of cancer. A human hepatocellular carcinoma cell line,
      HepG2, strongly adheres to human umbilical vein endothelial cells (HUVECs)
      through the interaction of E-selectin and its carbohydrate ligand sialyl Lewis X.
      In this study, we investigated alteration in integrin expression on HepG2 cells,
      which follows the selectin-mediated initial adhesion of HepG2 cells to HUVECs.
      Expression of alpha2beta1 integrin was markedly increased when the HepG2 cells
      adhered to HUVECs. Among the tested cytokines that are known to be produced by
      endothelial cells, recombinant hepatocyte growth factor (rHGF) could replace the
      effect of HUVECs, and a similar increase in integrin expression was observed by
      the addition of 20 ng ml-1 rHGF to HepG2. The increment of alpha2beta1 integrin
      expression was significantly inhibited by anti-HGF neutralizing antibody
      treatment. HepG2 cells expressed alpha2, alpha6, beta1, and beta4 integrin
      subunits, but expression of integrins other than alpha2beta1 was not affected by
      the rHGF treatment. The rHGF treatment of HepG2 cells resulted in augmented
      adhesion to immobilized collagen. This augmentation in adhesion to collagen was
      completely blocked by the addition of anti-alpha2- or anti-beta1-integrin
      antibody. In double-chamber chemoinvasion experiments, transmigration of the
      HepG2 cells through extracellular matrix (ECM) gel was significantly accelerated
      by co-cultivation with HUVECs. A similar level of enhancement in transmigration
      activity of the cancer cells was observed by the addition of rHGF. Our
      interpretation of the results described above is that the cancer cells received
      stimulation from cytokines, such as HGF, presented by vascular endothelial cells,
      following the initial adhesion of cancer cells via selectins. This resulted in
      the secondary increment in the expression of cell adhesion molecules, such as the
      alpha2beta1 integrin, and led to the augmented adhesive activities of cancer
      cells towards extracellular matrices at vascular walls. We suggest that this
      sequence of events is involved in the facilitated migration of some cancer cells
      to extravascular tissues.

PMID- 9000600
TI  - Characterization of a polymorphism in NAD(P)H: quinone oxidoreductase (DT
      diaphorase).
AB  - NAD(P)H:quinone oxidoreductase (NQO1, EC 1.6.99.2) is an obligate two-electron
      reductase that can either bioactivate or detoxify quinones and has been proposed
      to play an important role in chemoprevention. We have previously characterized a
      homozygous point mutation in the BE human colon carcinoma cell line that leads to
      a loss of NQO1 activity. Sequence analysis showed that this mutation was at
      position 609 of the NQO1 cDNA, conferring a proline to serine substitution at
      position 187 of the NQO1 enzyme. Using polymerase chain reaction (PCR) analysis,
      we have found that the H596 human non-small-cell lung cancer (NSCLC) cell line
      has elevated NQO1 mRNA, but no detectable enzyme activity. Sequencing of the
      coding region of NQO1 from the H596 cells showed the presence of the identical
      homozygous point mutation present in the BE cell line. Expression and
      purification of recombinant wild-type and mutant protein from E. coli showed that
      mutant protein could be detected using immunoblot analysis and had 2% of the
      enzymatic activity of the wild-type protein. PCR and Northern blot analysis
      showed moderate to low levels of expression of the correctly sized transcript in
      the mutant cells. Immunoblot analysis also revealed that recombinant mutant
      protein was immunoreactive; however, the mutant protein was not detected in the
      cytosol of either BE or H596 cells, suggesting that the mutant proteins were
      either not translated or were rapidly degraded. The absence of any detectable,
      active protein, therefore, appears to be responsible for the lack of NQO1
      activity in cells homozygous for the mutation. A polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis for the mutation at
      position 609 conducted on 90 human lung tissue samples (45 matched sets of tumour
      and uninvolved tissue) revealed a 7% incidence of individuals homozygous for the
      mutation, and 42% heterozygous for the mutation. These data suggest that the
      mutation at position 609 represents a polymorphism in an important xenobiotic
      metabolizing enzyme, which has implications for cancer therapy, chemoprevention
      and chemoprotection.

PMID- 9000601
TI  - Ca125 and neuron-specific enolase (NSE) as tumour markers for intra-abdominal
      desmoplastic small round-cell tumours.
AB  - Seven consecutive patients with intra-abdominal desmoplastic small round-cell
      tumours were screened at presentation for carcinoembryonic antigen (CEA), Ca19-9,
      Ca15-3, Ca125, alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and
      neuron-specific enolase (NSE). Initially elevated tumour markers were used to
      monitor therapy and follow-up. Tumour marker assays were all in the normal range,
      with the exception of Ca125 and NSE. The Ca125 level was initially high in six of
      the seven patients (86%) with a median value of 200 U ml-1 and a range of 22-735
      U ml-1. The NSE value was elevated before therapy in three of the five patients
      (60%) for whom assay results were available, with a median of 19 ng ml-1 and a
      range of 6.8-37.5 ng ml-1 . Ca1 25 normalized in five out of six cases and NSE
      always normalized during chemotherapy, but neither of these two tumour markers
      correlated specifically with response, as only one patient experienced a partial
      response, five tumour stabilization and the remaining patient tumour progression.
      At progression, Ca125 was again elevated in two out of four cases several weeks
      before clinical relapse and NSE in only one out of three cases. Ca125 and NSE are
      frequently raised in the serum of patients with intra-abdominal desmoplastic
      small round-cell tumours before therapy, but are not reliable monitors of the
      course of the disease. However, normalization is frequently associated with an
      improvement of symptoms or a moderate clinical response.

PMID- 9000603
TI  - p53 and Rb1 protein expression: are they prognostically useful in colorectal
      cancer?
AB  - The expression of the p53 and Rb1 proteins was examined in an unselected
      consecutive series of 250 primary operable colorectal carcinomas with a mean
      follow-up of 4.3 years (range 43-77 months). The overall cancer-specific
      mortality was 34.8%, with 87 cancer deaths and 35 deaths as the result of other
      causes. Expression of p53 protein was identified in 152 of 250 (60.8%) cases,
      with expression of Rb1 protein in 207 of 250 (82.8%) cases. There was no
      association of p53 or Rb protein expression with patient age, sex, tumour site,
      tumour size, tumour type, tumour grade, peritumoral fibrosis, tumour lymphocytic
      infiltrate, nature of the tumour margin, extramural vascular invasion, number of
      lymph nodes or high apical lymph node involved or local peritoneal infiltration
      by tumour, Dukes' stage or Jass group. There was no difference in overall
      survival or recurrence-free survival for those cases that showed p53 expression
      or Rb1 protein expression compared with those cases showing absence of p53 or Rb1
      protein expression, although patients with tumours showing aberrant (reduced) Rb1
      protein expression demonstrated shorter recurrence-free survival and overall
      survival. The effect of 'aberrant' Rb1 protein expression and shorter recurrence
      free and overall survival did not, however, achieve independent statistical
      significance. The results from this study would suggest that expression of p53
      and Rb1 proteins does not appear be useful in determining the prognosis of
      operable colorectal cancer.

PMID- 9000602
TI  - Small-cell lung cancer is characterized by a high incidence of deletions on
      chromosomes 3p, 4q, 5q, 10q, 13q and 17p.
AB  - The genetic mechanisms that define the malignant behaviour of small-cell lung
      cancer (SCLC) are poorly understood. We performed comparative genomic
      hybridization (CGH) on 22 autoptic SCLCs to screen the tumour genome for genomic
      imbalances. DNA loss of chromosome 3p was a basic alteration that occurred in all
      tumours. Additionally, deletions were observed on chromosome 10q in 94% of
      tumours and on chromosomes 4q, 5q, 13q and 17p in 86% of tumours. DNA loss was
      confirmed by loss of heterozygosity (LOH) analysis for chromosomes 3p, 5q and
      10q. Simultaneous mutations of these six most abundant genetic changes were found
      in 12 cases. One single tumour carried at least five deletions. DNA under
      representations were observed less frequently on chromosome 15q (55%) and
      chromosome 16q (45%). The prevalent imbalances were clearly indicated by the
      superposition of the 22 tumours to a CGH superkaryogram. In our view, the high
      incidence of chromosomal loss is an indication that SCLC is defined by a pattern
      of deletions and that the inactivation of multiple growth-inhibitory pathways
      contributes in particular to the aggressive phenotype of that type of tumour.

PMID- 9000604
TI  - Flow cytometric S-phase fraction in soft-tissue sarcoma: prognostic importance
      analysed in 160 patients.
AB  - We could determine the S-phase fraction (SPF) by flow cytometric DNA analysis of
      paraffin archival material in 160 of 260 patients with soft-tissue sarcoma of
      extremity and trunk wall. The prognostic value of SPF was compared with other
      clinicopathological factors. The median follow-up time was 16 (6-31) years. In a
      univariate analysis, deep tumour location, increasing tumour size and
      histological malignancy grade, microscopic tumour necrosis, vascular invasion,
      DNA non-diploidy and high SPF (>3.0%) were associated with poor metastasis-free
      survival. In a multivariate analysis, microscopic tumour necrosis and high SPF
      were independently prognostic for metastasis. Used in combination with tumour
      size, microscopic tumour necrosis and vascular invasion, SPF could identify a
      group of patients with a 5-year metastasis-free survival rate of 0.97. This group
      constituted one-quarter of all patients. Patients with low SPF who did recur had
      a prolonged clinical course both as regards metastases and local recurrence. We
      conclude that SPF is a valuable adjunct in prognostication in soft-tissue
      sarcoma.

PMID- 9000605
TI  - A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in
      patients with carcinoma of unknown primary site or advanced
      oesophagogastric/pancreatic adenocarcinomas.
AB  - Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies.
      Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic
      adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2,
      minimum life expectancy of 3 months and measurable disease. The regimen consisted
      of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5
      and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was
      repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with
      escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous
      level had been assessed. The maximum tolerated dose (MTD) was defined as the
      dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and
      symptomatic responses, quality of life and survival were assessed. The MTD of 5
      FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic
      marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic
      deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at
      350 mg m-2 after four courses. The objective response rate was 25% with one
      complete response (CR) and nine partial responses (PRs). The median duration of
      response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in
      CUPS patients. Twelve patients developed progressive disease on LCF. Median
      survival for all 40 patients was 7.8 months (10 months median survival for those
      treated at 350 mg m-2). The majority of patients described a symptomatic
      improvement with LCF chemotherapy. The recommended dose of 5-FU for future
      studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5).

PMID- 9000606
TI  - Changes in nutritional status associated with unresectable pancreatic cancer.
AB  - Weight loss is common in patients with pancreatic cancer; however, the nature and
      progress of their nutritional depletion are not well documented. In this study,
      pre-illness weight and duration of weight loss were recorded in 20 patients with
      histologically confirmed unresectable cancer of the pancreas. Patients then
      underwent nutritional analysis at monthly intervals until death. The median
      period of assessment was 27 weeks (interquartile range 22.5-38.0 weeks). At the
      time of diagnosis, all patients had lost weight [median 14.2% (10.0-20.0%) of pre
      illness stable weight], and this weight loss was progressive, increasing to a
      median of 24.5% by the time of the last assessment (P =0.0004). Body mass index
      was significantly reduced from a pre-illness median value of 24.9 kg m-2 (22.4
      27.4 kg m-2) to 20.7 kg m-2 (19.5-23.6 kg m-2) at the time of diagnosis and
      further to 17.7 kg m-2 (16.6-23.1 kg m-2) just before death (P =0.0003). Further
      evidence of tissue depletion was evident from the significant reductions in lean
      body mass [43.4 kg (36.9-53.0 kg) to 40.1 kg (33.5-50.7 kg) P =0.008] and fat
      mass [12.5 kg (8.9-17.8 kg) to 9.6 kg (6.3-15.1 kg) P =0.03). This study confirms
      that the majority of patients with unresectable pancreatic cancer have already
      undergone significant weight loss by the time of diagnosis and that the natural
      history of this process is one of inexorable progression. These results highlight
      the need for selective non-toxic therapeutic intervention to attenuate cachexia
      and indicate that such interventions should be instituted early in the course of
      the disease.

PMID- 9000607
TI  - Prognostic factors for disease progression in advanced Hodgkin's disease: an
      analysis of patients aged under 60 years showing no progression in the first 6
      months after starting primary chemotherapy.
AB  - The aim of this study was to determine whether a very high-risk group based on
      presenting characteristics could be identified in patients with advanced
      Hodgkin's disease who may benefit from high-dose chemotherapy (HDCT). Between
      1975 and 1992, 453 previously untreated patients aged under 60 years who did not
      progress in the first 6 months after the start of standard chemotherapy had their
      hospital notes reviewed. The outcomes analysed were early disease progression (in
      the 6- to 18-month window following the start of chemotherapy) and disease
      progression in the whole of the follow-up period. A Cox regression analysis was
      used to investigate the combined effects of a number of presenting
      characteristics on these outcomes. Despite the presence of factors with
      significant effects on the relative rate of progression, the absolute effects in
      a group identified as having the poorest prognosis were not especially poor. No
      group could be defined with a freedom from progression rate of less than 70% over
      6-18 months, and the worst prognostic group, which included only 53 patients, had
      an overall freedom from progression rate of 57% at 5 years. Four other reported
      prognostic indices were evaluated using our data set, but none of the indices was
      more successful in identifying a very high-risk group. It has not been possible
      to define a sufficiently high-risk group of patients with Hodgkin's disease based
      on presenting characteristics for whom HDCT could be advised as part of primary
      treatment. The search for more discriminating prognostic factors identifying
      vulnerable patients with a high risk of relapse must continue before a role can
      be found for HDCT following conventional chemotherapy in patients without disease
      progression.

PMID- 9000608
TI  - Second malignancy in patients with Hodgkin's disease treated at the Royal Marsden
      Hospital.
AB  - Risk of second primary malignancy was assessed in follow-up to June 1991 of 1039
      patients first treated for Hodgkin's disease at the Royal Marsden Hospital during
      1963-91. A total of 77 second malignancies occurred. There were significantly
      raised risks of stomach [standardized incidence ratio (SIR)=4.0], lung (SIR=3.8),
      bone (SIR=26.5), soft tissue (SIR=16.9) and non-melanoma skin (SIR=3.9) cancers,
      non-Hodgkin's lymphoma (SIR=4.6), and acute and non-lymphocytic leukaemia
      (SIR=31.3), with a relative risk of 3.3 for all second cancers other than non
      melanoma skin cancer. Solid cancer risk was raised to a similar extent in
      patients treated only with radiotherapy (SIR=2.6, P<0.001), only with
      chemotherapy (SIR=2.1, P=0.08) and with both (SIR=3.1, P<0.001). Leukaemia risk
      was raised only in those receiving chemotherapy, whether alone or with
      radiotherapy. The relative risk for solid cancers was much greater in patients
      who were younger at first treatment (trend P<0.001), whereas leukaemia risk was
      greatest for those first treated at ages 25-44. For solid cancers (P<0.001) but
      not leukaemia (P=0.05) there was a strong gradient of greater relative risks at
      younger attained ages. The relative risk of second cancers overall was 27.5 at
      ages under 25 and 2.0 at ages 55 and above. Leukaemia and solid cancer risks in
      patients treated with chlorambucil, vinblastine, procarbazine and prednisone
      (ChlVPP) were not significantly greater than those in patients treated with
      mustine, vincristine, procarbazine and prednisone (MOPP). Number of cycles of
      chemotherapy was significantly related to risk of leukaemia (P<0.001), and there
      was a trend in the same direction for solid cancers (P=0.07). The study adds to
      evidence that alkylating chemotherapy may increase the risk of solid cancers, and
      that ChlVPP does not provide a less carcinogenic alternative to MOPP
      chemotherapy. The very large relative risks found for solid cancers at young
      attained ages and in patients treated when young may have important implications
      as, in the long term, the majority of second malignancies after Hodgkin's disease
      are solid cancers. The risks of solid malignancies need clarification by larger
      collaborative epidemiological studies.

PMID- 9000609
TI  - Non-progression of cervical intraepithelial neoplasia estimated from population
      screening data.
AB  - Non-progression and duration of preclinical neoplastic lesions of the cervix
      uteri were studied using screening data from a previously unscreened population,
      Maribo County, Denmark (1966-82). To estimate regression rates, the incidence of
      clinical cancer before the screening programme was related to the prevalence and
      incidence of preclinical lesions estimated from the detection rates of first
      smear and third and subsequent smears respectively. Duration was estimated from
      the time lag between the cumulative incidence of preclinical lesions and the
      combined cumulative incidence of clinical cancer and the estimated 'incidence of
      regression'. Of all preclinical lesions in women aged 25-50, 24% progressed, 39%
      regressed and 38% remained. Even if we assume no onset of preclinical lesions
      above age 50, we estimated that 48% of the preclinical lesions would not progress
      to clinical cancer in the women's lifetime. The estimated mean duration of
      preclinical lesions was 16 years. In Maribo County during the 1970s, the positive
      rate (1.6%) was low compared with current rates in several countries. We conclude
      that the detection of non-progressive lesions was outweighed by the prevention of
      clinical cancer.

PMID- 9000610
TI  - Continued inadequacies in data sources for the evaluation of cancer services.
AB  - There is a need to evaluate cancer services and provide a baseline on current
      treatment success and organization. This study shows that this process may be
      severely hindered by case note destruction or inaccessibility and incomplete
      information. This is an ongoing problem that needs to be addressed now.

PMID- 9000611
TI  - Childhood cancer and parental use of tobacco: deaths from 1953 to 1955.
AB  - Parental smoking data have been abstracted from the interview records of the case
      control study that first indicated that pregnancy radiographs are a cause of
      childhood cancer (Oxford Survey of Childhood Cancers, deaths from 1953 to 1955).
      Reported smoking habits for the parents of 1549 children who died from cancer
      were compared with similar information for the parents of 1549 healthy controls
      (matched pairs analysis). There was a statistically significant positive trend
      between paternal daily consumption of tobacco and the risk of childhood cancer
      (P< 0.001). This association could not be explained by maternal smoking, social
      class, paternal or maternal age at the birth of the survey child, sibship
      position or obstetric radiography. About 15% of all childhood cancers in this
      series could be attributable to paternal smoking.

PMID- 9000612
TI  - Oral contraceptive use at a young age and the risk of breast cancer: an
      Icelandic, population-based cohort study of the effect of birth year.
AB  - The possible association between breast cancer and oral contraceptive use before
      the age of 20 was investigated using Icelandic population-based information from
      women born after 1944. The design was a nested case-control study within a
      cohort, using data on duration of oral contraceptive use at young ages. The
      availability of oral contraceptives before the age of 20 has changed dramatically
      and is highly dependent on birth years, with 20% and 82% starting before the age
      of 20 among Icelandic users born in 1945-47 and 1963-67 respectively. The
      association between total duration of oral contraceptive use and breast cancer
      was significantly dependent on year of birth. In women born in 1951-67 (based on
      81 cases), the relative risk (RR) associated with use for more than 4 years was
      2.0 (95% CI 1.1-3.7). The association disappeared when women born in 1945-50 were
      included (RR 1.1,95% CI 0.8-1.6), adding 123 cases. A significant trend of
      increased risk with longer duration was present only in the group born after
      1950, with RR 0.9, 1.7 and 3.0 for < or = 4 years, >4-8 years and > 8 years of
      use respectively. The results of this study indicate an association between
      breast cancer and oral contraceptive use at a young age. They also stress the
      importance of distinguishing between groups with different opportunities for
      exposure at young age.

PMID- 9000613
TI  - Psychological stress, cancer incidence and mortality from non-malignant diseases.
AB  - Psychological stress has been claimed to contribute to the onset of cancer and to
      increase mortality from a number of non-malignant diseases. We investigated the
      effect of a genuine psychological stressor, i.e. cancer in a child, on the
      incidence of cancer and mortality from non-malignant diseases of 11,231 parents
      in a Danish nationwide population-based study. The children were identified from
      records in the Danish Cancer Registry for the period 1943-85; their parents were
      identified from population registers. Overall, 1665 parental malignancies were
      diagnosed from the date the cancer of the child was reported until 1992, compared
      with 1702 expected from national incidence rates, yielding standardized incidence
      ratios of 1.0 (95% confidence interval, 0.9-1.0) for all parents, 1.0 for mothers
      and 1.0 for fathers. No statistically significant deviation of the relative risk
      from unity was seen for any period of follow-up after the stressful event, and no
      excess risk was seen for any particular type of cancer. Moreover, a total of 2137
      parental deaths were observed over the period 1974-92, compared with 2333
      expected from national mortality rates, giving an overall standardized mortality
      ratio of 0.9 (range 0.9-1.0). No excess mortality was seen from causes associated
      with allergic illness, autoimmune conditions, chronic illness or changes in
      behaviour. Our data provide no support for the hypothesis of an association
      between psychological stress and the incidence of cancer or mortality from non
      malignant diseases. We conclude that the human organism is highly adaptable, even
      to extreme psychological stress.

PMID- 9000614
TI  - Vitamins C and E, retinol, beta-carotene and dietary fibre in relation to breast
      cancer risk: a prospective cohort study.
AB  - Association between breast cancer risk and the intake of vitamins C and E,
      retinol, beta (beta)-carotene, dietary fibre, vegetables, fruit and potatoes was
      examined in The Netherlands Cohort Study, for 62,573 women aged 55-69 years.
      After 4.3 years of follow-up, 650 incident breast cancer cases were identified.
      After adjusting for traditional risk factors, breast cancer risk was not
      influenced by the intake of beta-carotene, vitamin E, dietary fibre, supplements
      with vitamin C, vegetables or potatoes. Fruit consumption showed a non
      significant inverse association with breast cancer risk (RR highest/lowest
      quintile = 0.76, 95% CI 0.54-1.08). A small reduction in risk was also observed
      with increasing intake of dietary vitamin C (RR highest/lowest quintile = 0.77,
      95% CI 0.55-1.08). For retinol, a weak positive association was observed (RR
      highest/lowest quintile = 1.24, 95% CI 0.83-1.83). Among subjects with a high
      intake of polyunsaturated fatty acids (PUFAs), both beta-carotene and vitamin C
      intake showed a non-significant inverse association with breast cancer risk (P
      trend = 0.15 and 0.16 respectively). Our findings do not suggest a strong role,
      if any, for intake of vitamins C and E, beta-carotene, retinol, dietary fibre,
      vegetables, fruit and potatoes in the aetiology of breast cancer.

PMID- 9000615
TI  - Molecular cloning and subcellular localisation of the snRNP-associated protein
      69KD, a structural homologue of the proto-oncoproteins TLS and EWS with RNA and
      DNA-binding properties.
AB  - We recently isolated and characterised a 69 kDa protein (69KD) found associated
      with spliceosomal small nuclear ribonucleoproteins (snRNPs). Here, we report the
      molecular cloning of a cDNA encoding this protein, its nucleic acid binding
      properties and its subcellular localisation. Sequence analysis of the 69KD cDNA
      revealed: (1) that 69KD shares structural similarity with the human RNA binding
      proteins TLS and EWS (95% and 65% identity, respectively), the products of two
      genes frequently targeted by tumour-specific chromosomal translocations; (2) that
      69KD contains a consensus RNA binding domain (CS-RBD) and three Arg/Gly-rich RNA
      binding motifs, structural features typical of many RNA binding proteins, in
      particular of hnRNP proteins; and (3) that 69KD contains a single putative
      Cys2/Cys2 zinc finger domain, a characteristic of many DNA-binding proteins.
      Consistent with its possession of these motifs, 69KD display a general nucleic
      acid binding activity, with a strong preference for guanyl and uridyl-rich RNA
      sequences, as well as for single-stranded and double-stranded DNA. The functional
      significance of this affinity for nucleic acids remains unclear. However, based
      on the established association of 69KD with the Sm core domain of snRNPs in vivo,
      these motifs might help mediate 69KD binding to snRNPs or be involved in some, as
      yet, unknown aspect of RNA metabolism. Consistent with both possibilities, 69KD
      is detected within typical snRNP containing subnuclear structures referred to as
      speckles, and is also more widely distributed throughout the nucleoplasm, as
      observed for many hnRNP proteins.

PMID- 9000616
TI  - On the role of the multiple regulatory elements involved in the activation of the
      Escherichia coli malEp promoter.
AB  - Activation of malEp and malKp, two divergent promoters from Escherichia coli,
      depends on the synergistic action of MalT and CRP. The reaction involves a common
      regulatory region located in between and comprising multiple binding elements for
      both regulatory proteins. The binding of MalT and CRP to this region is known to
      result in the formation of a higher-order structure that is responsible for malKp
      activation. This paper presents genetic data which together with previous
      results, provide compelling evidence that this higher-order structure is also
      responsible for malEp activation. The role(s) that this structure or elements
      thereof play in the activation of malEp is analysed by monitoring both the
      occupancy of the proximal MalT sites (sites 1 and 2) and the activity of
      different malEp variants in strains containing increasing amounts of active MalT.
      A truncated malEp promoter comprising only MalT sites 1 and 2 forms a minimal
      MalT-dependent promoter whose activity is limited by the occupancy of these
      sites. One role of the higher-order structure formed by MalT and CRP when bound
      to the entire regulatory region is to ensure high occupation of MalT sites 1 and
      2, but it is not its only function. Some elements of this structure, namely the
      CRP site 1, located at -76.5, and the distal MalT sites, seem to play a direct
      role in malEp activation besides their participation in the assembly of the
      higher-order structure.

PMID- 9000617
TI  - Structural change in Rev responsive element RNA of HIV-1 on binding Rev peptide.
AB  - The HIV-1 Rev responsive element (RRE) high-affinity binding site was studied by
      homonuclear and heteronuclear NMR. Two Rev binding element (RBE) RNA
      oligonucleotides were used as model systems in this study: RBE3, which contains
      the wild-type Rev high-affinity binding site, and RBE3-A which is identical
      except for the deletion of a bulged A. The temperature dependence of the two
      dimensional spectra of the free RNAs indicates that at lower temperatures more
      than one conformation is present. However, at higher temperatures a single
      conformation predominates. Model structures of RBE3 and RBE3-A as well as the
      RBE3-A complexed with a peptide derived from the RNA binding domain of HIV-1 Rev,
      were calculated using NMR-derived restraints. The Rev high-affinity binding site
      of the HIV-1 RRE contains a structured internal loop with two purine-purine base
      pairs and an extrahelical U. Comparison of the free and bound RNA structures
      reveals that upon peptide binding there is a distinct change in the backbone at
      G24, which is involved in a G-G base-pair. In the free RNA, G24 is in the syn
      conformation, and the backbone is in a relatively normal configuration,
      antiparallel to the other strand. In the bound RNA, the backbone at G24 has
      flipped over so that it is parallel to the other strand. G24 in the bound RNA
      still forms a base-pair with G6, but is now in the anti conformation.

PMID- 9000618
TI  - Interactions between RuvA and RuvC at Holliday junctions: inhibition of junction
      cleavage and formation of a RuvA-RuvC-DNA complex.
AB  - The RuvAB and RuvC enzymes of Escherichia coli define a molecular pathway for the
      resolution of Holliday intermediates in recombination and DNA repair. They bind
      specifically to Holliday junctions, and catalyse their branch migration and
      cleavage, respectively. In a RuvA(B)-junction complex, the Holliday structure is
      held in an open (square planar) configuration on the concave surface of a 4-fold
      symmetrical tetramer of RuvA, whereas in a RuvC-junction complex it is folded in
      an alternative arrangement as part of the cleavage reaction. Genetic studies have
      shown that the activity of RuvC in vivo depends on RuvAB, which suggests that the
      two enzymes act in concert, with junction cleavage by RuvC following from branch
      migration by RuvAB. We have investigated how RuvC can take over a junction from
      RuvAB to cleave the DNA. We show that RuvA inhibits junction cleavage by RuvC,
      probably by sandwiching the junction between two tetramers. The extent of
      inhibition depends on the reaction kinetics of RuvA binding relative to RuvC
      binding and cleavage. The presence of RuvB and the concentration of Mg2+ both
      have a significant effect on cleavage in the presence of RuvA. However, a novel
      protein-DNA complex can be formed when junction DNA is incubated with both RuvA
      and RuvC. Its mobility is consistent with a RuvC dimer binding to a junction held
      in an open configuration on the surface of a RuvA tetramer. We suggest that this
      arrangement provides RuvC with the means to scan the junction during the RuvAB
      mediated branch migration reaction for DNA sequences that it can cleave. We
      further suggest that recognition of the target may provide a trigger for
      dissociating RuvA, allowing the junction to be folded and cleaved by RuvC.

PMID- 9000619
TI  - Regulation of the activity of the type IC EcoR124I restriction enzyme.
AB  - Restriction-modification (R-M) systems must regulate the expression of their
      genes so that the chromosomal genome is modified at all times by the
      methyltransferase to protect the host cell from the potential lethal action of
      the cognate restriction endonuclease. Since type I R-M systems can be transferred
      to non-modified Escherichia coli cells by conjugation or transformation without
      killing the recipient, they must have some means to regulate their restriction
      activity upon entering a new host cell to avoid restriction of unprotected host
      DNA and cell death. This is especially true for EcoR124I, a type IC family
      member, which is coded for by a conjugative plasmid. Control of EcoR124I
      restriction activity is most likely at the post-translational level as the
      transfer of the EcoR124I system into a recipient cell that already expressed the
      HsdR subunit of this system was not a lethal event. Additionally, the kinetics of
      restriction activity upon transfer of the genes coding for the EcoR124I RM system
      to a recipient cell are the same, irrespective of the modification state of the
      recipient cell or the presence or absence of the EcoR124I HsdR subunit in the new
      host cells. The mechanism controlling the restriction activity of a type IC R-M
      system upon transfer to a new host cell is different from that controlling the
      chromosomally coded type IA and IB R-M systems. The previously discovered hsdC
      mutant, which affects the establishment of the type IA system EcoKI, was shown to
      affect the establishment of the type IB system EcoAI, but to have no influence on
      EcoR124I.

PMID- 9000620
TI  - Surface topographies at subnanometer-resolution reveal asymmetry and sidedness of
      aquaporin-1.
AB  - Aquaporin-1 (AQP1) is an abundant protein in human erythrocyte membranes which
      functions as a specific and constitutively active water conducting pore.
      Solubilized and isolated as tetramer, it forms well-ordered two-dimensional (2D)
      crystals when reconstituted in the presence of lipids. Several high resolution
      projection maps of AQP1 have been determined, but information on its three
      dimensional (3D) mass distribution is sparse. Here, we present surface reliefs at
      0.9 nm resolution that were calculated from freeze-dried unidirectionally metal
      shadowed AQP1 crystals as well as surface topographs recorded with the atomic
      force microscope of native crystals in buffer solution. Our results confirm the
      3D map of negatively stained AQP1 crystals, which exhibited tetramers with four
      major protrusions on one side and a large central cavity on the other side of the
      membrane. Digestion of AQP1 crystals with carboxypeptidase Y, which cleaves off a
      5 kDa intracellular C-terminal fragment, led to a reduction of the major
      protrusions, suggesting that the central cavity of the tetramer faces the outside
      of the cell. To interpret the results, sequence based structure predictions
      served as a guide.

PMID- 9000621
TI  - Scanning force microscopy of DNA deposited onto mica: equilibration versus
      kinetic trapping studied by statistical polymer chain analysis.
AB  - This paper reports a study of the deposition process of DNA molecules onto a mica
      surface for imaging under the scanning force microscope (SFM). Kinetic
      experiments indicate that the transport of DNA molecules from the solution drop
      onto the surface is governed solely by diffusion, and that the molecules are
      irreversibly adsorbed onto the substrate. A statistical polymer chain analysis
      has been applied to DNA molecules to determine the deposition conditions that
      lead to equilibrium and those that result in trapped configurations. Using the
      appropriate conditions, DNA molecules deposited onto freshly cleaved mica, are
      able to equilibrate on the surface as in an ideal two-dimensional solution. A
      persistence length of 53 nm was determined from those molecules. DNA fragments
      that were labeled on both ends with a horseradish peroxidase streptavidin fusion
      protein were still able to equilibrate on the surface, despite the additional
      protein-surface interaction. In contrast, DNA molecules deposited onto glow
      discharged mica or H+-exchanged mica do not equilibrate on the surface. These
      molecules adopt conformations similar to those expected for a simple projection
      onto the surface plane, suggesting a process of kinetic trapping. These results
      validate recent SFM application to quantitatively analyze the conformation of
      complex macromolecular assemblies deposited on mica. Under equilibration
      conditions, the present study indicates that the SFM can be used to determine the
      persistence length of DNA molecules to a high degree of precision.

PMID- 9000622
TI  - Structure and assembly properties of the intermediate filament protein vimentin:
      the role of its head, rod and tail domains.
AB  - We have investigated the functional role of the non-helical end domains of
      vimentin on its assembly properties using truncated Xenopus and human recombinant
      proteins. Removal of the amino-terminal "head" domain yielded a molecule that did
      not assemble into 10 nm filaments but remained in a soluble oligomeric particle
      form with a sedimentation coefficient considerably smaller than that of wild-type
      vimentin (Vim(wt)). In contrast, removal of the carboxy-terminal "tail" domain
      had no obvious effect on the sedimentation characteristics. In particular,
      sedimentation equilibrium analysis under low ionic strength conditions yielded
      oligomeric particle species of Mr 135,000 to 360,000, indistinguishable from
      those obtained with Vim(wt). When induced to form filaments from this state by
      rapid dilution into filament forming buffer, Vim(wt) and Vim(deltaT) protein
      generated similar viscosity profiles. However, as determined by scanning
      transmission electron microscopy, under these conditions Vim(deltaT) formed
      filaments of heterogeneous diameter, corresponding to various distinct mass-per
      length (MPL) values: whereas Vim(wt) yielded MPL values peaking between 40 and 45
      kDa/nm, Vim(deltaT) filaments produced histograms which could be fitted by three
      Gaussian curves peaking between 37 and 131 kDa/nm. In contrast, when dialyzed
      against, instead of being rapidly diluted into, filament forming buffer,
      Vim(deltaT) gave histograms with one major peak at about 54 kDa/nm. The MPL
      heterogeneity observed for Vim(deltaT) was already evident at the earliest stages
      of assembly. For example, ten seconds after initiation, "unit-length" filament
      segments (58 to 63 nm) were formed with both wt and deltaT proteins, but the
      diameters were considerably larger for Vim(deltaT) compared to Vim(wt) (20(+/- 3)
      nm versus 16(+/- 3)nm), indicating a distinct role of the carboxy-terminal tail
      domain in the width control during unit-length filament formation. Despite this
      difference both Vim(deltaT) and Vim(wt) filaments appeared to grow stepwise in a
      modular fashion from such unit-length filament segments. This suggests that
      assembly occurred by a principally similar mechanism involving the end-on-fusion
      or annealing of unit-length filaments.

PMID- 9000623
TI  - Sequential headful packaging and fate of the cleaved DNA ends in bacteriophage
      SPP1.
AB  - The virulent Bacillus subtilis bacteriophage SPP1 packages its DNA from a
      precursor concatemer by a headful mechanism. Following disruption of mature
      virions with chelating agents the chromosome end produced by the headful cut
      remains stably bound to the phage tail. Cleavage of this tail-chromosome complex
      with restriction endonucleases that recognize single asymmetric positions within
      the SPP1 genome yields several distinct classes of DNA molecules whose size
      reflects the packaging cycle they were generated from. A continuous decrease in
      the number of molecules within each class derived from successive encapsidation
      rounds indicates that there are several packaging series which end after each
      headful packaging cycle. The frequency of molecules in each packaging class
      follows the distribution expected for a sequential mechanism initiated
      unidirectionally at a defined position in the genome (pac). The heterogeneity of
      the DNA fragment sizes within each class reveals an imprecision in headful
      cleavage of approximately 2.5 kb (5.6% of the genome size). The number of
      encapsidation events in a packaging series (processivity) was observed to
      increase with time during the infection process. DNA ejection through the tail
      can be induced in vitro by a variety of mild denaturing conditions. The first DNA
      extremity to exit the virion is invariably the same that was observed to be bound
      to the tail, implying that the viral chromosome is ejected with a specific
      polarity to penetrate the host. In mature virions a short segment of this
      chromosome end (55 to 67 bp equivalent to 187 to 288 A) is fixed to the tail area
      proximal to the head (connector). Upon ejection this extremity is the first to
      move along the tail tube to exit from the virion through the region where the
      tail spike was attached.

PMID- 9000624
TI  - A network of heterogeneous hydrogen bonds in GNRA tetraloops.
AB  - RNA hairpin loops containing a GNRA consensus sequence are the most frequently
      occurring hairpins in a variety of prokaryotic and eukaryotic RNAs. These
      tetraloops play important functional roles in RNA folding, in RNA-RNA tertiary
      interactions and as protein binding sites. Homo and heteronuclear NMR
      spectroscopy have been used to determine the structures of the most abundant
      members of the GNRA tetraloop family: the GAGA, GCAA and GAAA loops closed by a C
      G base pair. Analysis of the structures of these three hairpin loops reveals a
      network of heterogeneous hydrogen bonds. The loops contain a G-A base pair, a G
      base-phosphate hydrogen bond and several 2' OH-base hydrogen bonds. These
      intramolecular interactions and the extensive base stacking in the loop help
      explain the high thermodynamic stability and give insight into the diverse
      biological roles of the GNRA RNA hairpins.

PMID- 9000625
TI  - Hairpin loops consisting of single adenine residues closed by sheared A.A and G.G
      pairs formed by the DNA triplets AAA and GAG: solution structure of the
      d(GTACAAAGTAC) hairpin.
AB  - The DNA undecamers GTACAAAGTAC (AAA 11-mer) and GTACGAGGTAC (GAG 11-mer) have
      been studied in solution by high-resolution NMR spectroscopy. Both duplexes form
      stable hairpins containing single deoxyadenosine loops and stems containing five
      base-pairs that are closed at the loop end by sheared AxA and GxC pairs,
      respectively. These molecules thus contain new AAA and GAG loop turn motifs. All
      protons, including the chiral H5'/H5" protons of the loop residues, were assigned
      using NOESY, DQF-COSY and heteronuclear 1H-31P COSY experiments. The backbone
      torsion angles were constrained using experimental data from NOE crosspeaks,
      three-bond 1H-1H coupling constants and four-bond 1H-31P coupling constants and
      four-bond 1H-31P coupling constants. The AAA and GAG 11-mers form similar
      structures in solution. The detailed structure of the AAA 11-mer was determined
      by the combined use of NMR, distance geometry and energy minimization methods.
      This structure exhibits good stacking of the loop adenosine base on the closing
      5Ax7A sheared pair, with the 6A base stacking on the 5A base and the 6A
      deoxyribose stacking with the 7A base. All sugars in the AAA 11-mer hairpin adopt
      the typical DNA C2'-endo conformation and a sharp backbone turn occurs between
      residues 6A and 7A. This loop turn is brought about mainly by a change in the
      backbone phosphate torsion angles from zeta(g-) alpha(g-) to zeta(g+) alphat(g+)
      at the turn. The gamma torsion angle of residue 7A in the closing sheared pair
      also changes from gauche+ to trans. In Pu1NPu2 loop turns of the GCA, AAA and GAG
      types, the chemical shift of the H4' proton of the loop deoxyribose depends on
      the nature of Pu2; this reflects the stacking of the loop sugar on the Pu2 base
      and the different ring current effects of A or G in this position.

PMID- 9000626
TI  - Structural role of a buried salt bridge in the 434 repressor DNA-binding domain.
AB  - The independently folding 63-residue N-terminal DNA-binding domain of the 434
      repressor, 434(1-63), contains a buried Arg10-Glu35 salt bridge. A corresponding
      salt bridge is found in a variety of prokaryotic and eukaryotic DNA-binding
      proteins with helix-turn-helix motifs. Here, the NMR solution structures of 434(1
      63) and the mutant protein 434[R10M](1-63) were determined to investigate the
      structural role of this salt bridge. Both proteins contain the same type of
      global fold, with five alpha-helices and a helix-turn-helix motif formed by the
      helices II and III. The primary structural difference caused by the Arg10 --> Met
      mutation is a translation of helix I along its axis relative to the helix II-turn
      helix III motif. This limited conformational change is paralleled by a 9 kJ M(-1)
      decrease of the stability of the folded mutant protein in aqueous solution at pH
      4.8. It affects the pKa value of Glu19 as well as the population of a hydrogen
      bond between the backbone amide proton of Asn16 and the side-chain carboxylate
      group of Glu19. Using the crystal structure of the 434 repressor dimer complexed
      with the operator DNA as a basis, model building of the DNA complex with the NMR
      structure of 434[R10M](1-63) shows that Asn16, which is located on the protein
      surface, makes direct contact with the DNA and indicates that the point mutation
      Arg10 --> Met should also lead to modifications of the protein-protein contacts
      in the complex.

PMID- 9000627
TI  - Crystal structures of adenylosuccinate synthetase from Escherichia coli complexed
      with GDP, IMP hadacidin, NO3-, and Mg2+.
AB  - Crystal structures of adenylosuccinate synthetase from Esherichia coli complexed
      with Mg2+, IMP, GDP, NO3- and hadacidin at 298 and 100 K have been refined to R
      factors of 0.188 and 0.206 against data to 2.8 A and 2.5 A resolution,
      respectively. Conformational changes of up to 9 A relative to the unligated
      enzyme occur in loops that bind to Mg2+, GDP, IMP and hadacidin. Mg2+ binds
      directly to GDP, NO3-, hadacidin and the protein, but is only five-coordinated.
      Asp13, which approaches, but does not occupy the sixth coordination site of Mg2+,
      hydrogen bonds to N1 of IMP. The nitrogen atom of NO3- is approximately 2.7 A
      from O6 of IMP, reflecting a strong electrostatic interaction between the
      electron-deficient nitrogen atom and the electron-rich O6. The spatial
      relationships between GDP, NO3- and Mg2+ suggest an interaction between the
      beta,gamma-bridging oxygen atom of GTP and Mg2+ in the enzyme-substrate complex.
      His41 hydrogen bonds to the beta-phosphate group of GDP and approaches bound NO3
      . The aldehyde group of hadacidin coordinates to the Mg2+, while its carboxyl
      group interacts with backbone amide groups 299 to 303 and the side-chain of
      Arg303. The 5'-phosphate group of IMP interacts with Asn38, Thr129, Thr239 and
      Arg143 (from a monomer related by 2-fold symmetry). A mechanism is proposed for
      the two-step reaction governed by the synthetase, in which His41 and Asp13 are
      essential catalytic side-chains.

PMID- 9000628
TI  - Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on
      the crystal structure of its complex with ribonuclease A.
AB  - We describe the mechanism of ribonuclease inhibition by ribonuclease inhibitor, a
      protein built of leucine-rich repeats, based on the crystal structure of the
      complex between the inhibitor and ribonuclease A. The structure was determined by
      molecular replacement and refined to an Rcryst of 19.4% at 2.5 A resolution.
      Ribonuclease A binds to the concave region of the inhibitor protein comprising
      its parallel beta-sheet and loops. The inhibitor covers the ribonuclease active
      site and directly contacts several active-site residues. The inhibitor only
      partially mimics the RNase-nucleotide interaction and does not utilize the p1
      phosphate-binding pocket of ribonuclease A, where a sulfate ion remains bound.
      The 2550 A2 of accessible surface area buried upon complex formation may be one
      of the major contributors to the extremely tight association (Ki = 5.9 x 10(-14)
      M). The interaction is predominantly electrostatic; there is a high chemical
      complementarity with 18 putative hydrogen bonds and salt links, but the shape
      complementarity is lower than in most other protein-protein complexes.
      Ribonuclease inhibitor changes its conformation upon complex formation; the
      conformational change is unusual in that it is a plastic reorganization of the
      entire structure without any obvious hinge and reflects the conformational
      flexibility of the structure of the inhibitor. There is a good agreement between
      the crystal structure and other biochemical studies of the interaction. The
      structure suggests that the conformational flexibility of RI and an unusually
      large contact area that compensates for a lower degree of complementarity may be
      the principal reasons for the ability of RI to potently inhibit diverse
      ribonucleases. However, the inhibition is lost with amphibian ribonucleases that
      have substituted most residues corresponding to inhibitor-binding residues in
      RNase A, and with bovine seminal ribonuclease that prevents inhibitor binding by
      forming a dimer.

PMID- 9000629
TI  - Crystal structure of Arabidopsis thaliana NADPH dependent thioredoxin reductase
      at 2.5 A resolution.
AB  - Thioredoxin exists in all organisms and is responsible for the hydrogen transfer
      to important enzymes for ribonucleotide reduction and the reduction of methionine
      sulphoxide and sulphate. Thioredoxins have also been shown to regulate enzyme
      activity in plants and are also involved in the regulation of transcription
      factors and several other regulatory activities. Thioredoxin is reduced by the
      flavoenzyme thioredoxin reductase using NADPH. We have now determined the first
      structure of a eukaryotic thioredoxin reductase, from the plant Arabidopsis
      thaliana, at 2.5 A resolution. The dimeric A. thaliana thioredoxin reductase is
      structurally similar to that of the Escherichia coli enzyme, and most differences
      occur in the loops. Because the plant and E. coli enzymes have the same
      architecture, with the same dimeric structure and the same position of the redox
      active disulphide bond, a similar mechanism that involves very large domain
      rotations is likely for the two enzymes. The subunit is divided into two domains,
      one that binds FAD and one that binds NADPH. The relative positions of the
      domains in A. thaliana thioredoxin reductase differ from those of the E. coli
      reductase. When the FAD domains are superimposed, the NADPH domain of A. thaliana
      thioredoxin reductase must be rotated by 8 degrees to superimpose on the
      corresponding domain of the E. coli enzyme. The domain rotation we now observe is
      much smaller than necessary for the thioredoxin reduction cycle.

PMID- 9000630
TI  - Ribosomal protein L9: a structure determination by the combined use of X-ray
      crystallography and NMR spectroscopy.
AB  - The structure of protein L9 from the Bacillus stearothernophilus ribosome has
      been determined at 2.5 A resolution by refinement against single crystal X-ray
      diffraction data with additional constraints provided by NMR data. This highly
      elongated protein consists of two domains separated by a nine-turn connecting
      helix. Conserved aromatic and positively charged amino acid residues on the
      surface of each domain are likely to be directly involved in binding 23 S
      ribosomal RNA. The shape of the protein, with its two widely spaced RNA-binding
      sites, suggests that it may serve as a "molecular strut", most likely playing a
      role in ribosome assembly and/or maintaining the catalytically active
      conformation of the ribosomal RNA. The combined use of X-ray and NMR data in the
      refinement procedure was essential in defining the N-terminal domain of the
      protein, which was relatively poorly determined by the X-ray data alone. In
      addition to resolving the ambiguities in defining the hydrophobic core and side
      chain conformations with the N-terminal domain, this combined NMR-X-ray analysis
      provides the first detailed and accurate view of the N-terminal RNA-binding site.
      NMR data also showed that the N-terminal domain is stable in solution, indicated
      by amide protons that are protected from solvent exchange. The lack of definition
      of the N-terminal domain in the X-ray structure is therefore likely due to
      packing disorder within the crystal rather than structural instability. This
      combined NMR-X-ray analysis provides a useful model as to how X-ray and NMR data
      can be practically and logically combined in the determination of the structure
      of a single protein molecule.

PMID- 9000631
TI  - The crystal structure of a hyperthermophilic archaeal TATA-box binding protein.
AB  - This study analyzes the three-dimensional structure of the TATA-box binding
      protein (TBP) from the hyperthermophilic archaea Pyrococcus woesei. The crystal
      structure of P. woesei TBP (PwTBP) was solved at 2.2 A by X-ray diffraction and
      as expected from sequence homology (36% to 41% identical to eukaryotic TBPs) its
      overall structure is very similar to eukaryotic TBPs. The thermal unfolding
      transition temperature of this protein was measured by differential scanning
      calorimetry to be 101 degrees C, which is more than 40 degrees C higher than that
      of yeast TBP. Preliminary titration calorimetry data show that the affinity of
      PwTBP for its DNA target, unlike its eukaryotic counterparts, is enhanced by
      increasing the temperature and salt concentration. The structure reveals possible
      explanations for this thermostability and these unusual DNA binding properties.
      The crystal structure of this hyperthermostable protein was compared to its
      mesophilic homologs and analyzed for differences in the native structure that may
      contribute to thermostability. Differences found were: (1) a disulfide bond not
      found in mesophilic counterparts; (2) an increased number of surface
      electrostatic interactions; (3) more compact protein packing. The presumed DNA
      binding surface of PwTBP, like its eukaryotic counterparts, is hydrophobic but
      the electrostatic profile surrounding the protein is relatively neutral compared
      to the asymmetric positive potential that surrounds eukaryotic TBPs. The total
      reliance on a hydrophobic interface with DNA may explain the enhanced affinity of
      PwTBP for its DNA promoter at higher temperatures and increased salt
      concentration.

PMID- 9000632
TI  - Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8
      Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is an
      important target for chemotherapeutic agents used in the treatment of AIDS; the
      TIBO compounds are potent non-nucleoside inhibitors of HIV-1 RT (NNRTIs). Crystal
      structures of HIV-1 RT complexed with 8-Cl TIBO (R86183, IC50 = 4.6 nM) and 9-Cl
      TIBO (R82913, IC50 = 33 nM) have been determined at 3.0 A resolution. Mutant HIV
      1 RT, containing Cys in place of Tyr at position 181 (Tyrl81Cys), is highly
      resistant to many NNRTIs and HIV-1 variants containing this mutation have been
      selected in both cell culture and clinical trials. We also report the crystal
      structure of Tyrl81Cys HIV-1 RT in complex with 8-Cl TIBO (IC50 = 130 nM)
      determined at 3.2 A resolution. Averaging of the electron density maps computed
      for different HIV-1 RT/NNRTI complexes and from diffraction datasets obtained
      using a synchrotron source from frozen (-165 degrees C) and cooled (-10 degrees
      C) crystals of the same complex was employed to improve the quality of electron
      density maps and to reduce model bias. The overall locations and conformations of
      the bound inhibitors in the complexes containing wild-type HIV-1 RT and the two
      TIBO inhibitors are very similar, as are the overall shapes and volumes of the
      non-nucleoside inhibitor-binding pocket (NNIBP). The major differences between
      the two wild-type HIV-1 RT/TIBO complexes occur in the vicinity of the TIBO
      chlorine substituents and involve the polypeptide segments around the beta5-beta6
      connecting loop (residues 95 to 105) and the beta13-beta14 hairpin (residues 235
      and 236). In all known structures of HIV-1 RT/NNRTI complexes, including these
      two, the position of the beta12-beta13 hairpin or the "primer grip" is
      significantly displaced relative to the position in the structure of HIV-1 RT
      complexed with a double-stranded DNA and in unliganded HIV-1 RT structures. Since
      the primer grip helps to position the template-primer, this displacement suggests
      that binding of NNRTIs would affect the relative positions of the primer terminus
      and the polymerase active site. This could explain biochemical data showing that
      NNRTI binding to HIV-1 RT reduces efficiency of the chemical step of DNA
      polymerization, but does not prevent binding of either dNTPs or DNA. When the
      structure of the Tyr181Cys mutant HIV-1 RT in complex with 8-Cl TIBO is compared
      with the corresponding structure containing wild-type HIV-1 RT, the overall
      conformations of Tyr181Cys and wild-type HIV-1 RT and of the 8-Cl TIBO inhibitors
      are very similar. Some positional changes in the polypeptide backbone of the
      beta6-beta10-beta9 sheet containing residue 181 are observed when the Tyr181Cys
      and wild-type complexes are compared, particularlty near residue Val179 of beta9.
      In the p51 subunit, the Cys181 side-chain is oriented in a similar direction to
      the Tyr181 side-chain in the wild-type complex. However, the electron density
      corresponding to the sulfur of the Cys181 side-chain in the p66 subunit is very
      weak, indicating that the thiol group is disordered, presumably because there is
      no significant interaction with either 8-Cl TIBO or nearby amino acid residues.
      In the mutant complex, there are slight rearrangements of the side-chains of
      other amino acid residues in the NNIBP and of the flexible dimethylallyl group of
      8-Cl TIBO; these conformational changes could potentially compensate for the
      interactions that were lost when the relatively large tyrosine at position 181
      was replaced by a less bulky cysteine residue. In the corresponding wild-type
      complex, Tyr181 iin the p66 subunit has significant interactions with the bound
      inhibitor and the position of the Tyr181 side-chain is well defined in both
      subunits. Apparently the Tyr181 --> Cys mutation eliminates favorable contacts of
      the aromatic ring of the tyrosine and the bou

PMID- 9000633
TI  - Characterizing the use of perdeuteration in NMR studies of large proteins: 13C,
      15N and 1H assignments of human carbonic anhydrase II.
AB  - Perdeuteration of all non-exchangeable proton sites can significantly increase
      the size of proteins and protein complexes for which NMR resonance assignments
      and structural studies are possible. Backbone 1H, 15N, 13CO, 13C alpha and 13C
      beta chemical shifts and aliphatic side-chain 13C and 1H(N)/15N chemical shifts
      for human carbonic anhydrase II (HCA II), a 259 residue 29 kDa metalloenzyme,
      have been determined using a strategy based on 2D, 3D and 4D heteronuclear NMR
      experiments, and on perdeuterated 13C/15N-labeled protein. To date, HCA II is one
      of the largest monomeric proteins studied in detail by high-resolution NMR. Of
      the backbone resonances, 85% have been assigned using fully protonated 15N and
      3C/15N-labeled protein in conjunction with established procedures based on now
      standard 2D and 3D NMR experiments. HCA II has been perdeuterated both to
      complete the backbone resonance assignment and to assign the aliphatic side-chain
      13C and 1H(N)/15N resonances. The incorporation of 2H into HCA II dramatically
      decreases the rate of 13C and 1H(N)T2 relaxation. This, in turn, increases the
      sensitivity of several key 1H/13C/15N triple-resonance correlation experiments.
      Many otherwise marginal heteronuclear 3D and 4D correlation experiments, which
      are important to the assignment strategy detailed herein, can now be executed
      successfully on HCA II. Further analysis suggests that, from the perspective of
      sensitivity, perdeuteration should allow other proteins with rotational
      correlation times significantly longer than HCA II (tau c = 11.4 ns) to be
      studied successfully with these experiments. Two different protocols have been
      used to characterize the secondary structure of HCA II from backbone chemical
      shift data. Secondary structural elements determined in this manner compare
      favorably with those elements determined from a consensus analysis of the HCA II
      crystal structure. Finally, having outlined a general strategy for assigning
      backbone and side-chain resonances in a perdeuterated large protein, we propose a
      strategy whereby this information can be used to glean more detailed structural
      information from the partially or fully protonated protein equivalent.

PMID- 9000635
TI  - Thermal unfolding of the DNA-binding protein Sso7d from the hyperthermophile
      Sulfolobus solfataricus.
AB  - Thermal unfolding of the small hyperthermophilic DNA-binding protein Sso7d was
      studied by circular dichroism spectroscopy and differential scanning calorimetry.
      The unfolding transition can be described by a reversible two state process.
      Maximum stability was observed in the region between pH 4.5 and 7.0 where Sso7d
      unfolds with a melting temperature between 370.8 to 371.9 K and an unfolding
      enthalpy between 62.9 and 65.4 kcal/mol. The heat capacity differences between
      the native and the heat denatured states obtained by differential scanning
      calorimetry (620 cal/(molK)) and circular dichroism spectroscopy (580 cal/(mol
      K)) resulted in comparable values. The thermodynamic reason for the high melting
      temperature of Sso7d is the shallow stability curve with a broad free energy
      maximum, corresponding to the relatively small heat capacity change which was
      obtained. The calculated stability curve shows that Sso7d has, despite of its
      high melting temperature, an only moderate intrinsic stability, which reaches its
      maximum (approximately 7 kcal/mol) at 282 K. Sso7d is particularly poorly
      stabilized (approximately 1 kcal/mol) at the maximum physiological growth
      temperature of Sulfolobus solfataricus. Sso7d has furthermore untypically low
      specific enthalpy (0.99 kcal/(mol residue)) and entropy (2.99 cal/(mol K)) values
      at convergence temperatures. No significant differences in thermal stability of
      the partially methylated Sso7d from Sulfolobus solfataricus and the cloned non
      methylated form of the protein expressed in Escherichia coli were observed.

PMID- 9000634
TI  - Three-dimensional structure of the HTLV-II matrix protein and comparative
      analysis of matrix proteins from the different classes of pathogenic human
      retroviruses.
AB  - The matrix protein performs similar roles in all retroviruses, initially
      directing membrane localization of the assembling viral particle and subsequently
      forming a stable structural shell associated with the inner surface of the mature
      viral membrane. Although conserved structural elements are likely to perform
      these functions in all retroviral matrix proteins, invariant motifs are not
      evident at the primary sequence level and three-dimensional structures have been
      available for only the primate lentiviral matrix proteins. We have therefore used
      NMR spectroscopy to determine the structure of the matrix protein from human T
      cell leukemia virus type II (HTLV-II), a member of the human oncovirus subclass
      of retroviruses. A total of 577 distance restraints were used to build 20 refined
      models that superimpose with an rmsd of 0.71 A for the backbone atoms of the
      structured regions. The globular HTLV-II matrix structure is composed of four
      alpha-helices and a 3(10) helix. Exposed basic residues near the C terminus of
      helix II form a putative membrane binding surface which could act in concert with
      the N-terminal myristoyl group to anchor the protein on the viral membrane
      surface. Clear structural similarities between the HTLV-II and HIV-1 matrix
      proteins suggest that the topology and exposed cationic membrane binding surface
      are likely to be conserved features of retroviral matrix proteins.

PMID- 9000636
TI  - Phenylalanine 353 is a primary determinant for the positional specificity of
      mammalian 15-lipoxygenases.
AB  - Mammalian lipoxygenases are implicated in the biosynthesis of inflammatory
      mediators, in the pathogenesis of atherosclerosis and in the process of blood
      cell differentiation and maturation. With respect to their reaction specificity,
      three major types of mammalian lipoxygenases (15-lipoxygenases, 12-lipoxygenases
      and 5-lipoxygenases) may be classified. Although this nomenclature is commonly
      used, the mechanistic reasons for the positional specificity of lipoxygenases are
      not well understood. We investigated the structural reasons for lipoxygenase
      specificity by a combination of chimera formation and site-directed mutagenesis,
      and identified phenylalanine 353 as primary determinant for the positional
      specificity of rabbit reticulocyte 15-lipoxygenase. Modeling of the enzyme
      substrate interaction suggested that the alignment of arachidonic acid at the
      active site appears to be influenced by this residue. According to the substrate
      orientation, the 15-lipoxygenase may be differentiated from two types of
      mammalian 12-lipoxygenases.

PMID- 9000637
TI  - Site-directed mutagenesis of the catalytic residues of bovine pancreatic
      deoxyribonuclease I.
AB  - Bovine pancreatic deoxyribonuclease I (DNase I) is a well characterised
      endonuclease which cleaves double-stranded DNA to yield 5' phosphorylated
      polynucleotides. Co-crystal structures of DNase I with two different
      oligonucleotides have revealed the presence of several residues (R9, E78, H134,
      D168, D212 and H252) close to the scissile phosphate. The roles that these amino
      acids play in the catalytic mechanism have been investigated using site-directed
      mutagenesis. The following variants were used: R9A, E78T, H134Q, D168S, D212S and
      H252Q. The kinetics of all six mutants with both DNA and a small chromophoric
      substrate, thymidine-3',5'-di(p-nitrophenyl)-phosphate, were studied. Only R9A
      and E78T showed any significant turnover of the two substrates. D168S, H134Q,
      D212S and H252Q showed vanishingly low activities towards DNA and no detectable
      activity with thymidine-3',5'-di(p-nitrophenyl)-phosphate. These results
      demonstrate that H134, D168, D212 and H252 play a critical role in the catalytic
      mechanism. It is suggested that H134 and H252 (which are hydrogen-bonded to E78
      and D212, respectively) provided general acid and general base catalysis. DNase I
      also requires Mg2+ and E39 has been identified as a ligand for this metal ion. We
      propose that D168 serves as a ligand for a second Mg2+, and thus DNase I, uses a
      two metal-ion hydrolytic mechanism. Both magnesium ions are used to supply
      electrophilic catalysis. Role assignment is based on the mutagenesis results,
      structural information, homologies between DNase I from different species and a
      comparison with exonuclease III. However, it is still not feasible to
      unequivocally assign a particular catalytic role to each amino acid/metal ion.

PMID- 9000638
TI  - How to derive a protein folding potential? A new approach to an old problem.
AB  - In this paper we introduce a novel method of deriving a pairwise potential for
      protein folding. The potential is obtained by an optimization procedure that
      simultaneously maximizes thermodynamic stability for all proteins in the
      database. When applied to the representative dataset of proteins and with the
      energy function taken in pairwise contact approximation, our potential scored
      somewhat better than existing ones. However, the discrimination of the native
      structure from decoys is still not strong enough to make the potential useful for
      ab initio folding. Our results suggest that the problem lies with pairwise amino
      acid contact approximation and/or simplified presentation of proteins rather than
      with the derivation of potential. We argue that more detail of protein structure
      and energetics should be taken into account to achieve energy gaps. The suggested
      method is general enough to allow us to systematically derive parameters for more
      sophisticated energy functions. The internal control of validity for the
      potential derived by our method is convergence to a unique solution upon addition
      of new proteins to the database. The method is tested on simple model systems
      where sequences are designed, using the preset "true" potential, to have low
      energy in a dataset of structures. Our procedure is able to recover the potential
      with correlation r approximately 91% with the true one and we were able to fold
      all model structures using the recovered potential. Other statistical knowledge
      based approaches were tested using this model and the results indicate that they
      also can recover the true potential with high degree of accuracy.

PMID- 9000639
TI  - Deviations from planarity of the peptide bond in peptides and proteins.
AB  - The work described here is the result of a survey of the peptide omega angles in
      the Cambridge Structural Database of small molecules, which was carried out to
      establish "ideal" or "target" values for their distribution. We have shown that
      substantial deviations from planarity can be tolerated with a standard deviation
      in the angle of up to 6 degrees about a mean value for the trans peptide that is
      less than 180 degrees . The distortion can arise from pyramidalization at the
      amino nitrogen atom as well as simple twist about the peptide bond. We include an
      analysis of omega angles in the existing database of protein structure (PDB) and
      show that their distributions can depend on the refinement method used, but no
      correlation with resolution is evident. A surprising finding was a systematic
      variation of omega in phi,psi space in proteins as well as in the linear and
      cyclic peptides. This is particularly manifest as a consistent difference between
      the mean omega values in chains of left and right-hand chirality. This dichotomy
      is observed for all the standard amino acids and is especially striking in the
      absence of secondary structure. The phenomenon is discussed in the context of
      theoretical work on peptide analogues, and the implications for protein
      conformation and structure are briefly considered.

PMID- 9000640
TI  - DNA vaccines.
AB  - Immunization with plasmid DNA encoding antigenic proteins elicits both antibody
      and cell-mediated immune responses. This method of producing the protein antigens
      of interest directly in host cells can provide appropriate tertiary structure for
      the induction of conformationally specific antibodies, and also facilitates the
      induction of cellular immune responses. DNA immunization has provided effective
      protective immunity in various animal models. The immune responses induced by DNA
      vaccines may in some instances be preferable to those produced by immunization
      using conventional methods. DNA vaccination appears to be applicable to a variety
      of pathogens and is a useful method of raising immune responses. Thus this
      approach to vaccination has the potential to be a successful method of rapidly
      screening for antigens capable of inducing protective immunity, and of inducing
      protective immunity against pathogens of clinical importance.

PMID- 9000641
TI  - Decrease in oral bioavailability of cyclosporin A by coadministration of probucol
      in rats.
AB  - To assess the pharmacokinetic interaction of cyclosporin A with probucol, we
      administered cyclosporin A (10 mg/kg body weight) to rats orally or intravenously
      with or without pretreatment of probucol (10 mg/animal, daily for 8 days). The
      whole blood cyclosporin A concentration-time curves after oral administration
      showed a 34% reduction in peak concentration and a 30% decrease in area under the
      blood concentration-time curve (AUC) by administration of probucol. No apparent
      change in elimination half-life or volume of the central compartment was observed
      with the treatment of probucol. After intravenous administration of cyclosporin
      A, the blood levels could be described by a two-compartment open model. No
      differences were observed in the AUC, elimination half-life or total clearance of
      cyclosporin A by the pretreatment of probucol. Calculated bioavailability
      following oral administration of cyclosporin A decreased by 33% with the
      treatment of probucol. These results suggest that probucol may not profoundly
      influence the disposition of cyclosporin A. Coadministration of probucol could
      decrease the fraction of absorbed cyclosporin A after oral administration.

PMID- 9000642
TI  - Smooth muscle energetic in the pig coronary artery during a calcium-dependent and
      a calcium-independent isometric contraction.
AB  - Heat production by resting smooth muscle, was measured with a heat-flux micro
      calorimeter on cut-open segments of pig coronary artery superfused at 30 degrees
      C, was 0.93+/-0.06 (n=16) mW/g wet weight. Time courses of the increases in
      isometric tension and heat production with respect to basal during sustained
      supra maximal acetylcholine stimulation were qualitatively similar: initial peak
      tapering down to a supra basal plateau. Mean tension-associated heat production
      over 1 h was 0.16 J/g. During sustained exposure to phorbol 12,13-dibutyrate,
      supra basal tension and--with a 5-10 min initial delay--supra basal heat
      progressively increased to a plateau in about 40 min. Mean tension-associated
      heat production over 1 h was only 0.02 J/g with normal extracellular and
      intracellular mobilizable Ca2+ pools, and it was further reduced to 0.01 J/g with
      depleted Ca2+ pools. These results show that the maintenance--if not necessarily
      the building up--of tension under phorbol 12,13-dibutyrate does not entail any
      large dissipation of energy and is not dependent on the presence of normal Ca2+
      pools.

PMID- 9000644
TI  - Enhancement of oocyte growth in the cockroach Blaberus craniifer by a scorpion
      toxin, charybdotoxin.
AB  - We investigated the ovarian response of Blaberus craniifer to charybdotoxin in
      both imaginal molt headless females and isolated fed females, at three criteria.
      1--Vitellogenesis onset, detected by immunocytochemical localisation of sites
      binding anti-eggs antibodies in the basal oocyte in headless females: 60% of
      treated females present a positive response. 2--Oocyte length at D4 during
      vitellogenesis of isolated fed females which was enhanced by 0.1 - 0.2 microg
      toxin; doses higher than 0.5 microg/female decrease ovarian growth. 3--Time of
      oviposition of paired females which was shortened by 24 hrs by the toxin. These
      results suggest that low doses charybdotoxin enhance vitellogenesis, possibly via
      the nervous system by means of a substance conditioning both protein synthesis by
      the fat body and ovarian uptake.

PMID- 9000643
TI  - Lack of cystic fibrosis transmembrane regulator-type chloride current in
      pediatric human atrial myocytes.
AB  - Mature cardiomyocytes have been shown to possess a cyclic AMP-mediated chloride
      channel (I(Cl)) which is the product of the cystic fibrosis transmembrane
      regulator (CFTR) gene. Species variability has been demonstrated for other ion
      channels. This study was designed to evaluate human I(Cl) regulation using the
      whole-cell patch-clamp bioassay. Atrial tissue obtained from children undergoing
      congenital heart surgery was enzymatically dispersed into isolated myocytes. The
      patients ranged in age from 1 day to 11 years (mean 2 years). Isoproterenol was
      used to activate the cAMP second-messenger system in a potassium-free
      environment. Membrane calcium and sodium channels were pharmacologically blocked.
      Of 20 human atrial myocytes obtained from 13 pediatric patients, 80% had a small
      basal chloride current. The current could be inhibited by the anion transport
      blocker, 9-anthracene carboxylic acid. In 4 of 20 otherwise viable myocytes, no
      I(Cl) could be elicited, either at baseline or with beta-adrenergic stimulation.
      Of the 16 myocytes with a basal I(Cl), the current was unaffected by cAMP
      stimulation in 15 (94%) cells. There were no significant differences in age,
      gender or clinical status of patients whose cells conducted Cl- current compared
      with patients whose myocytes had no measurable I(Cl). Ten mature guinea pig
      ventricular myocytes were evaluated using the same whole-cell patch-clamp
      technique. Seven of 10 cells showed a reversible increase in I(Cl) with
      isoproterenol exposure. Despite presence of the CFTR gene in human
      cardiomyocytes, functional expression of the cAMP-activated I(Cl) does not appear
      evident in isolated pediatric atrial myocytes. Whether the pathophysiology of
      congenital heart disease may influence chloride current modulation via
      alterations in adrenergic tone, intracellular Ca2+ regulation, and cellular
      osmotic conditions remains to be established.

PMID- 9000645
TI  - Effects of licorice derivatives on vascular smooth muscle function.
AB  - Vascular smooth muscle contains a bidirectional form of the enzyme 11beta
      hydroxysteroid dehydrogenase (11beta-HSD) which can inactivate (dehydrogenase)
      endogenous circulating glucocorticoids (GCs) or activate (oxo-reductase) 11
      dehydro-metabolites by their conversion back to the parent steroid. Enzyme
      direction in vascular smooth muscle (VSM) has potential physiological
      consequences since GCs may enhance the response to known vasoconstrictors. We
      determined that carbenoxolone is a competitive inhibitor of 11beta-HSD contained
      in VSM cells with a lower Ki for forward dehydrogenase reaction (0.02 microM)
      compared to the oxo-reductase reaction (0.41 microM). To test whether changes in
      enzyme directional activity can affect the contractile response, aortae from
      adrenally intact Sprague Dawley rats were removed and sectioned into 2.5 mm
      rings. Rings were incubated with corticosterone 10 nM plus carbenoxolone (CBX) 10
      microM (a concentration well above the Ki for both the dehydrogenase and oxo
      reductase reaction) for 24 hrs. These rings showed an enhanced dose dependent
      contractile response to phenylephrine (PE) 0.01 microM(-1) microM and to
      angiotensin II 1 microM compared to rings incubated with corticosterone alone,
      CBX alone, or controls: [e.g. response to PE 1 microM in mg of contractile force,
      mean +/- SE: corticosterone plus CBX 1495 +/- 162 (n=10) vs corticosterone 1039
      +/- 64 (n=9), p<0.05]. Aortic rings preincubated with 11-dehydrocorticosterone
      10(-7)M and CBX 10 microM displayed a decreased contractile response compared to
      11-dehydrocorticosterone alone. Thus in situ glucocorticoid metabolism is
      important in mediating the constrictor responses of vascular tissue.

PMID- 9000646
TI  - Zymosan-activated plasma induces paw oedema by nitric oxide and prostaglandin
      production.
AB  - Injection of zymosan-activated plasma into the rat paw induced oedema formation.
      Subplantar injection of the non isoform- selective inhibitors of nitric oxide
      (NO) synthase, N(G)-nitro-L-Arginine methyl ester and N(G)-methyl-L-Arginine, and
      of a scavenger of NO, haemoglobin, inhibited the early phase of oedema
      development. Inhibition of cyclooxygenase activity by indomethacin reduced the
      late increase in paw volume after the injection of zymosan-activated plasma.
      Methylene blue, an inhibitor of the soluble guanylate cyclase, had no effect. Our
      results suggest that in paw oedema induced by zymosan-activated plasma, the
      inflammatory response is dependent on NO (for the early phase) and prostaglandins
      (for the late phase). The effect of NO is likely to be mediated by a pathway
      which does not involve cyclic GMP.

PMID- 9000648
TI  - A rapid and sensitive quantitation method of endogenous morphine in human plasma.
AB  - Endogenous morphine is found at very low levels (pg/ml) in human plasma. Without
      technical modification, the usual techniques, i.e., RIA or HPLC, can not directly
      detect its presence. As a result the initial purification process is very
      crucial. In this report we demonstrate this opiate alkaloids determination in 2
      ml of human plasma. Following an acidified precipitation of proteins in plasma, a
      solid-phase extraction, Sep-pak collection, was employed to concentrate the
      endogenous morphine. The extract was dissolved in a pH 8.9 phosphate buffer and
      then extracted into an organic solvent (chloroform and isopropyl alcohol). The
      initially purified sample was separated by HPLC and detected with an
      electrochemical detector of 500 mV and 0.02 Hz. The results showed that the
      recovery of morphine by this technique was 86+5.7%, and the sensitivity was 50
      pg/ml. Compared to the detection sensitivity of the HPLC (2 ng/ml), this method
      increased the detection limit by 40-fold. With this method the concentration of
      endogenous morphine in plasma was determined as 80 pg/ml.

PMID- 9000647
TI  - Effect of acute magnesium deficiency (MgD) on aortic endothelial cell (EC)
      oxidant production.
AB  - Magnesium deficiency (MgD) has been associated with production of reactive oxygen
      species, cytokines, and eicosanoids, as well as vascular compromise in vivo.
      Although MgD-induced inflammatory change occurs during "chronic" MgD in vivo,
      acute MgD may also affect the vasculature and consequently, predispose
      endothelial cells (EC) to perturbations associated with chronic MgD. As
      oxyradical production is a significant component of chronic MgD, we examined the
      effect of acute MgD on EC oxidant production in vitro. In addition we determined
      EC; pH, mitochondrial function, lysosomal integrity and general cellular
      antioxidant capacity. Decreasing Mg2+ (< or = 250microM) significantlyincreased
      EC oxidant production relative to control Mg2+ (1000microM). MgD-induced oxidant
      production, occurring within 30min, was attenuated by EC treatment with
      oxyradical scavengers and inhibitors of eicosanoid biosynthesis. Coincident with
      increased oxidant production were reductions in intracellular glutathione (GSH)
      and corresponding EC alkalinization. These data suggest that acute MgD is
      sufficient for induction of EC oxidant production, the extent of which may
      determine, at least in part, the extent of EC dysfunction/injury associated with
      chronic MgD.

PMID- 9000649
TI  - Memory enhancement mediated by the steroid sulfatase inhibitor (p-O-sulfamoyl)-N
      tetradecanoyl tyramine.
AB  - The intent of this study was to determine whether altering the metabolism of
      neurosteroids via blockade of the enzyme, steroid sulfatase, could enhance memory
      retention in rats. The steroid sulfatase inhibitor p-O-(sulfamoyl)-N
      tetradecanoyl tyramine (DU-14) was administered alone and in combination with the
      neurosteroid dehydroepiandrosterone sulfate (DHEAS) to rats which were then
      tested for the reversal of scopolamine-induced amnesia. A single 30 mg/kg IP dose
      of DU-14 produced a significant inhibition of steroid sulfatase activity in both
      brain (14.8%), and liver (85.2%) tissues, 24 hours following administration. In a
      passive avoidance test, DU-14 enhanced the reversal of amnesia by DHEAS. These
      results suggest that steroid sulfatase inhibition can potentiate the memory
      enhancing properties of DHEAS.

PMID- 9000650
TI  - Restoration of nitric oxide production by aldose reductase inhibitor in human
      endothelial cells cultured in high-glucose medium.
AB  - The effects of elevated glucose and aldose reductase inhibitor (ARI:ONO-2235) on
      nitric oxide (NO) production in cultured human umbilical endothelial cells
      (HUVEC) were evaluated. Aldose reductase and nitric oxide synthase(NOS) share
      NADPH as an obligate cofactor, therefore it is suggested that the enhanced of
      glucose flux (27.5 mM) by aldose reductase inhibited NO production by blunting
      NOS activity. However, the addition of ONO-2235 (100 microM) prevented the
      inhibition of [NO2-] production. Since ARI decreases glucose-mediated inhibition
      of NO production in HUVEC. this agent might ameliorate endothelial function
      associated with diabetes.

PMID- 9000651
TI  - Lysophosphatidylcholine induces Ca2+-independent cellular injury attenuated by d
      propranolol in rat cardiomyocytes.
AB  - In isolated rat cardiomyocytes, exogenous lysophosphatidylcholine (LPC) (15
      microM) increased the intracellular Ca2+ concentration (Ca2+]i) from 72 +/- 5 to
      3042 +/- 431 nM accompanied by cell injury as indicated by the hypercontracture
      of the cells and the increase in creatine phosphokinase (CPK) release. In order
      to understand whether the cell injury induced by LPC was a consequence of the
      elevation of [Ca2+]i, the effect of LPC was examined in the Ca2+-free solution
      containing EGTA. Under the Ca2+ -free conditions, LPC did not increase [Ca2+]i,
      whereas it still inflicted injury on the cells in terms of cell-shape change and
      CPK release to the same degree as that under the Ca2+-present condition. Addition
      of ryanodine (10 microM) failed to prevent the changes in cell-shape and CPK
      release induced by LPC under both Ca2+-free and Ca2+-present conditions.
      Preincubation of the myocytes with d-propranolol (50 microM) inhibited the LPC
      induced changes in cell-shape and CPK release under both Ca2+ -free and Ca2+ 
      present conditions (p < 0.05). Our study provides clear evidence that the
      cellular injury induced by LPC could be independent of the increase in [Ca2+]i,
      and the Ca2+-independent cellular injury induced by LPC could be attenuated by d
      propranolol, although the mechanism remains unknown.

PMID- 9000652
TI  - FN18-CRM9 immunotoxin promotes tolerance in primate renal allografts.
AB  - BACKGROUND: Transplant tolerance, rather than immunity, may be favored in the
      setting of a lower mature lymphoid mass in the recipient induced by anti-T cell
      agents. A novel immunosuppressive agent, FN18-CRM9, known to specifically kill T
      cells with great potency, was evaluated in a transplant model. METHODS: In order
      to ablate recipient T cells, the immunotoxin FN18-CRM9 was administered to rhesus
      monkey recipients of MHC-mismatched renal allografts. Donor lymphocytes were
      injected intrathymically into some animals. RESULTS: All monkeys with T-cell
      depletion by immunotoxin had prolonged allograft survival, and tolerance
      confirmed by skin grafting has been confirmed in five of six long-surviving
      recipients. CONCLUSIONS: In this clinically relevant model, profound but
      transient T-cell depletion by a single agent substantially promotes tolerance.

PMID- 9000653
TI  - High-dose donor bone marrow infusions to enhance allograft survival: the effect
      of timing.
AB  - BACKGROUND: The development of strategies to enhance survival of transplanted
      organs and to potentially lower or even discontinue immunosuppressive therapy
      would represent a significant advance in posttransplant patient care. The aim of
      this clinical trial was to determine the effect of timing and dose of peripheral
      donor bone marrow cell (DBMC) infusion on graft and patient survival after liver
      transplantation. METHODS: DBMC, obtained from vertebral bodies, were administered
      in 101 recipients of liver allografts (OLTX). There were 107 patients for whom
      DBMC could not be obtained; they received OLTX alone (controls). A total of 5 x
      10(8)/kg DBMC were infused at day 0 (group 1; n=9); at days 0 and 11 (group 2;
      n=26); or at days 5 and 11 (group 3; n=26). In group 4 (n=40), patients received
      up to five infusions of 2 x 10(8)/kg DBMC at days 5, 14, 21, 28, and 90 after
      OLTX. RESULTS: When the results from patients receiving two or more DBMC
      infusions (groups 2, 3, and 4) are considered, both patient and graft survival
      were significantly improved compared with the control group (P=0.02 and P=0.01,
      respectively). In groups 3 and 4, 88.5% and 95% of patients were alive with mean
      follow-up of 536 and 265 days, respectively, compared with 77.6% of patients in
      the control group (average follow-up of 452 days) (P=0.02). Graft survival was
      also significantly improved in groups 3 (88.5%) and 4 (92.5%), compared with the
      controls (72%) (P=0.007). CONCLUSIONS: The results suggest that dose and timing
      of DBMC infusions may be important variables affecting allograft survival. A
      randomized prospective trial is now in progress to compare group 3 DBMC infusion
      protocol with controls receiving OLTX alone.

PMID- 9000654
TI  - Recipient preconditioning and donor-specific bone marrow infusion in a pig model
      of total bowel transplantation.
AB  - BACKGROUND: In an outbred pig model of total bowel transplantation, we previously
      showed that simultaneous donor-specific bone marrow infusion (DSBMI), rather than
      promoting engraftment, sensitizes recipients and causes rejection; it also
      aggravates the risk of generalized graft-versus-host disease (GVHD) and
      infection, and tends to reduce recipient and graft survival. Small and large
      animal models of bone marrow-induced transplant tolerance suggest that some form
      of recipient preconditioning (RPC) may facilitate engraftment of co-transplanted
      bone marrow cells and fully expose their tolerogenic potential. METHODS: In a
      preclinical model, we prospectively studied the effect of RPC on simultaneous
      DSBMI and total (i.e., small and large) bowel transplantation. RPC consisted of
      whole body irradiation with 400 R (day 0); some recipients additionally received
      horse anti-pig antithymocyte globulin (days -2, -1, and 0). We studied six groups
      of outbred pigs, all of which underwent at least a total bowel transplant: group
      1, nonimmunosuppressed control pigs (n=5); group 2, nonimmunosuppressed DSBMI
      pigs (n=13); group 3, tacrolimus pigs (n=7); group 4, DSBMI+tacrolimus pigs
      (n=15); group 5, RPC+nonimmunosuppressed DSBMI pigs (n=11); and group 6,
      RPC+DSBMI+tacrolimus pigs (n=14). RESULTS: RPC did not prolong overall survival
      at 7, 14, 21, and 28 days after transplant. Survival rates were 100%, 100%, 86%,
      and 71% in group 3; 71%, 43%, 29%, and 29% in group 6; 55%, 9%, 0%, and 0% in
      group 5; and 60%, 0%, 0%, and 0% in Group 1. Moreover, RPC (groups 5 and 6)
      increased the incidence of death from rejection, GVHD, and infection when
      compared with group 3. Survival was significantly higher for RPC+DSBMI+tacrolimus
      pigs (group 6), compared with RPC+nonimmunosuppressed DSBMI pigs (group 5).
      Survival greater than 28 days was noted only in pigs that received tacrolimus
      after transplant: 71% in group 3 versus 29% in group 6. With both RPC and DSBMI
      (groups 5 and 6), rejection, GVHD, and infection were not mutually exclusive
      events. In groups 5 and 6, at autopsy, the incidence of rejection and GVHD was
      17%; rejection and infection, 17%; and GVHD and infection, 45%. A combination of
      all three immunologic events was noted in 14%. CONCLUSIONS: RPC, combined with
      DSBMI, and with or without posttransplant immunosuppression, does not prolong
      survival after total bowel transplantation. Rather, it increases the incidence of
      death from rejection, GVHD, infection, or a combination of these three
      immunologic events. According to this preclinical study, RPC and unmodified DSBMI
      do not improve patient and graft outcome after total bowel transplantation and
      need to be refined before being applied clinically.

PMID- 9000655
TI  - Sequential isologous organ transplantation in inbred rats: pancreaticoduodenal
      transplants.
AB  - A total of 847 inbred Lewis rats of mixed sex were used in this
      pancreaticoduodenal (Pd) donor aging study. Pd grafts were taken from 9- to 12
      month-old donors and transplanted into 3-month-old recipients (thus, the first
      generation Pd graft, or 1 Pd). After 9 to 12 months, the same Pd grafts were
      again harvested and transplanted into 3-month-old rats (thus the 2 Pd
      generation). This cycle was repeated to obtain the 3, 4, and 5 Pd series.
      Sequential transplantation was able to extend the Pd grafts' mean survival time
      to 32 months for fourteen 4 Pd grafts, and to 39.2 months for four 5 Pd grafts
      (the longest lived graft survived for 42 months). The pancreas and duodenal
      sections of the grafts remained normal throughout the entire study. However, the
      aortic sections of the grafts (which were harvested to include the superior
      mesenteric and celiac arteries) all exhibited moderate to massive atherosclerotic
      changes by the 5 Pd mean survival age of 39.2 months. Such histological changes
      commenced even before 21 months of Pd graft age in some animals, gradually
      progressing to dilation of the aorta (and subsequent narrowing of aortic
      tributaries), as well as formation of an eggshell-like inner membrane shielding
      the aortic intima, by 42 months. Such atherosclerotic changes precluded
      transplantations beyond the 5 Pd series.

PMID- 9000656
TI  - Molecular and cellular events implicated in local tolerance to kidney allografts
      in miniature swine.
AB  - Long-term tolerance to class I-mismatched renal allografts can be induced in
      miniature swine by treatment with a short course of cyclosporine (CsA). Kidney
      recipients treated with CsA and untreated control kidney recipients both
      demonstrated infiltration of the transplanted kidney by mononuclear cells, which
      reached a maximum between postoperative days 8 and 11. Recipients that did not
      receive the tolerizing regimen rejected their grafts between postoperative days 8
      and 12 in this model. The kinetics of cytokine gene expression, including
      interleukin (IL)-1alpha, IL-1beta, IL-2, IL-6, IL-10, tumor necrosis factor, and
      interferon-gamma (IFN-gamma), within the grafted kidney of rejector and acceptor
      animals, were determined using Northern blot hybridization. A strong correlation
      between rejection and up-regulation of the IFN-gamma gene was observed, whereas
      animals with long-term tolerance showed low levels of IFN-gamma, but high levels
      of IL-10 gene transcription. None of the other cytokine genes demonstrated a
      reproducible pattern of expression that correlated with acceptance/rejection of
      allografts. Analysis of transcription patterns of cytokine genes in mononuclear
      cells purified from renal grafts confirmed the initial observations made on
      biopsies. The phenotype of graft-infiltrating cells (GIC) showed a dominance of
      CD8+ cells, with an average of 66% single-positive cells and 19% CD4/CD8 double
      positive cells, compared with 30% and 14%, respectively, for peripheral cells.
      Predominance of CD8+ GIC was dictated neither by the MHC antigen disparity nor
      the rejector/acceptor status. These results, therefore, suggest that GIC
      represent a regulated combination of mononuclear cells producing local immune
      mediators that, in part, control the fate of allografts in this large animal
      model.

PMID- 9000657
TI  - A phase I trial of humanized anti-interleukin 2 receptor antibody in renal
      transplantation.
AB  - The efficacy of murine monoclonal anti-interleukin 2 alpha chain receptor (Tac)
      antibodies is limited by a short half-life and the development of antibodies to
      the heterologous protein. The safety, pharmacokinetics-dynamics, and
      immunosuppressive effect of a humanized anti-Tac antibody (HAT) was evaluated in
      12 renal transplant recipients. Ten patients received living related transplants
      (three HLA-identical matches and seven one-haplotype or zero-haplotype matches)
      and two patients received cadaver organs. The patients were divided into four HAT
      treatment arms: 0.5 mg/kg/week (n=4), 1 mg/kg/week (n=2), 0.5 mg/kg every other
      week (n=3), and 1 mg/kg every other week (n=3). The first dose of HAT was given
      within 12 hr before transplantation, and four additional doses were given after
      transplantation. Patients were also placed on cyclosporine, steroids, and
      azathioprine. Only one patient, a recipient of a cadaver kidney in the lowest HAT
      treatment arm, had a reversible rejection episode. The 10 recipients of living
      related transplants were compared with 17 historical controls treated with an
      identical immunosuppressive regimen except for HAT. Whereas none of the HAT
      treated living related donor recipients had a rejection episode, 6 of 17 (41%) of
      the historical controls had a rejection episode in the first year after
      transplantation. There were no first-dose reactions after HAT therapy or other
      subsequent side effects. None of the patients experienced opportunistic
      infections or malignancies. One patient developed low-titer anti-HAT antibodies,
      although the patient maintained high serum HAT concentrations throughout the
      study. Immune monitoring showed that there were no changes in the percentage or
      absolute counts of CD3 cells or T-cell subsets after HAT therapy. However, there
      was a significant decrease in the number of circulating lymphocytes that
      expressed free Tac. The overall harmonic mean half-life of HAT was 273 hr. The
      results of this study indicate that HAT given at 1 mg/kg every other week for a
      total of five doses may provide therapeutic HAT concentration levels and result
      in good saturation of Tac receptors for at least 12 weeks after transplantation.
      In summary, HAT is safe and is well tolerated by patients. Its long half-life and
      lack of immunization could make it a very useful immunosuppressive drug.

PMID- 9000659
TI  - Antibody screening by enzyme-linked immunosorbent assay using pooled soluble HLA
      in renal transplant candidates.
AB  - The enzyme-linked immunosorbent assay (ELISA) using HLA class I molecules
      purified from pooled platelets has the potential to detect HLA antibodies with
      increased efficiency without sacrificing sensitivity or specificity. This test,
      which was originally developed in our institution, has been independently
      validated by recent studies and is now commercially available. We now present
      evidence of its usefulness as a routine HLA antibody screening test for renal
      transplant patients. A total of 515 patients were tested monthly by ELISA (13.9
      tests/patient) and by antiglobulin-enhanced panel reactivity (6.3 tests/patient).
      In patients found to be unsensitized, the incidence of false-positive results was
      less for ELISA than for the panel studies. In patients who were highly
      sensitized, both tests performed equally well, whereas discordant results were
      registered mainly in cases of mild sensitization. Because 66% of our patients
      were not sensitized, the ELISA was effective in reducing the number of more
      involved tests aimed at characterizing the antibodies. These results provide a
      foundation to use the pooled platelet HLA ELISA on a routine basis for HLA
      antibody screening.

PMID- 9000658
TI  - Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis
      of three randomized, double-blind, clinical studies in prevention of rejection.
      The International Mycophenolate Mofetil Renal Transplant Study Groups.
AB  - BACKGROUND: The search for more effective and less toxic immunosuppressive agents
      to control transplant rejection has led to the extensive testing of mycophenolate
      mofetil (MMF) in clinical renal transplantation. METHODS: A pooled analysis of
      three phase III, randomized, double-blind, multicenter clinical trials conducted
      in the United States, Canada, Europe, and Australia was performed to further
      characterize the efficacy of MMF in renal allograft recipients. The three studies
      enrolled a total of 1493 patients. Triple- and quadruple-therapy regimens of
      cyclosporine, corticosteroids, and standardized MMF dosages with and without
      antilymphocyte induction were used: MMF in twice-daily doses of 1.0 g or 1.5 g
      (MMF 2 g or 3 g) was compared with placebo (PLA) or azathioprine (AZA). The
      primary efficacy endpoint in the individual trials was biopsy-proven rejection or
      treatment failure at 6 months. This pooled analysis focused on graft loss,
      patient death, incidence and treatment of rejection episodes, and graft function
      (serum creatinine) at 1 year. RESULTS: At 1 year, the graft survival rate was
      90.4% and 89.2% in the MMF 2 g and 3 g groups, respectively, compared with 87.6%
      in the PLA/AZA group. This difference was not statistically significant. MMF
      significantly reduced the incidence of rejection episodes: 40.8% for PLA/AZA
      patients versus 19.8% and 16.5% for the MMF 2 g and MMF 3 g groups, respectively.
      Renal function was consistently better for both MMF treatment groups at 3, 6, and
      12 months. CONCLUSIONS: MMF proved superior to AZA as a posttransplant
      immunosuppressant in conjunction with cyclosporine and corticosteroids. MMF
      treated groups showed reduced incidence and severity of rejection episodes,
      similar graft survival, and better graft function over 12 months.

PMID- 9000660
TI  - Endogenous interleukin 1 receptor antagonist during human bone marrow
      transplantation: increased levels during graft-versus-host disease, during
      infectious complications, and after immunoglobulin therapy.
AB  - In order to understand in more detail the role of endogenous interleukin 1
      receptor antagonist (IL-1ra) during bone marrow transplantation, IL-1ra serum
      levels of 28 patients undergoing allogeneic (n=25) or autologous (n=3) bone
      marrow transplantation were measured with a commercially available ELISA. In
      addition, the impact of intravenous immunoglobulin (IVIG) was evaluated by
      analyzing IL-1ra serum levels before and 2, 5, and 24 hr after IVIG infusion. IL
      1ra measurements revealed a nadir of circulating IL-1ra levels 3-5 days after
      bone marrow transplantation, with an increase during conditioning and
      hematological reconstitution. Circulating IL-1ra levels were significantly
      increased in patients with cytomegalovirus (CMV) disease, CMV reactivation, graft
      versus-host disease (GVHD), or fever of unknown origin, when compared with time
      matched controls without complications. Highest levels were observed in patients
      with CMV disease (1922+/-388 pg/ml), followed by patients with CMV reactivation
      (1575+/-435 pg/ml) and GVHD (1178+/-317 pg/ml). The magnitude of IL-1ra increase
      in GVHD was related to disease severity. Patients with grade III-IV GVHD
      developed higher IL-1ra levels than did patients with grade I-II GVHD. Lower but
      still significantly elevated IL-1ra levels were observed during fever of unknown
      origin (384+/-87 pg/ml). An increase of IL-1ra serum levels followed the
      administration of IVIG before transplantation and after hematopoietic
      reconstitution, but not during aplasia, pointing to the important role of
      hematopoietic cells in the production of IL-1ra. In conclusion, we show that IL
      1ra release is related to conditioning regimen, hematopoietic reconstitution,
      complications of infectious and alloimmune etiology after bone marrow
      transplantation, and exogenously administered IVIG.

PMID- 9000661
TI  - Analysis of HLA-DR split-specificity matching in cadaver kidney transplantation:
      a report of the Collaborative Transplant Study.
AB  - The influence of mismatches for HLA-DR "split" specificities was investigated in
      more than 8000 cadaver kidney transplants. HLA-DR typing was performed using DNA
      methodology. Among first transplants, mismatches defined by HLA-DR split
      specificities did not have a deleterious influence. Among retransplants, however,
      graft survival was significantly decreased if a mismatch was defined, considering
      split specificities in patients with no mismatch according to the "broad"
      definition (P=0.04) and also in grafts with two split mismatches, which showed
      only one mismatch according to the broad definition (P=0.03). Moreover,
      consideration of further "subsplit" specificities resulted in clinically relevant
      mismatches only among retransplants. These data indicate that the recognition of
      HLA-DR split specificity mismatches is fundamentally different in primary and
      regraft recipients. The results imply that recipients and donors of kidney
      retransplants should be typed for HLA-DR split specificities and that these
      specificities should be considered for organ allocation.

PMID- 9000662
TI  - Gastrointestinal bleeding after liver transplantation.
AB  - To investigate the causes of gastrointestinal bleeding (GIB) and its impact on
      patient and graft survival after orthotopic liver transplantation (OLTx), the
      first 1000 consecutive OLTx using tacrolimus were studied. Our patient population
      consisted of 834 adults. The bleeding episodes of patients with GIB (n=74) were
      analyzed, and patients without GIB (n=760) were used as controls. The mean age,
      gender, and United Network for Organ Sharing status were similar in both groups.
      Endoscopy was done in 73 patients with GIB and yielded a diagnosis in 60 patients
      (82.2%): 39 with a single, and 21 with multiple GIB episodes. In the remaining 13
      patients (17.8%), the bleeding source was not identified. Of 92 GIB episodes with
      endoscopic diagnoses, ulcers (n=25) were the most common cause of bleeding,
      followed by enteritis (n=24), portal hypertensive lesions (n=15), Roux-en-Y
      bleeds, and other miscellaneous events (n=28). The majority (73%) of the GIB
      episodes occurred during the first postoperative trimester. The patient and graft
      survival rates were statistically lower in the GIB group compared with the
      control group. The adjusted relative risk of mortality and graft failure was
      increased by bleeding. In summary, the cumulative incidence of GIB was 8.9%.
      Endoscopy identified the source of GIB in most cases. Ulcers were the most common
      cause of GIB after OLTx. The onset of GIB after OLTx was an indicator of
      decreased patient and graft survival.

PMID- 9000663
TI  - Patterns of viremia in liver transplant recipients with symptomatic
      cytomegalovirus infection.
AB  - Cytomegalovirus (CMV) titer in blood seems to be the principal determinant of
      clinical symptoms in immunosuppressed patients. We have developed an assay for
      quantitation of CMV DNA in serum. The assay requires the coamplification by
      polymerase chain reaction (PCR) of extracted serum DNA with 1000 molecules of
      mutated internal standard DNA, and then an ELISA detection system. We examined
      133 paired buffy coats and sera from 15 patients with symptomatic infection. Sera
      were examined by quantitative PCR, and buffy coats were examined by qualitative
      PCR (with a detection threshold of approximately 40 copies per 150,000 cells).
      Serum viral titers peaked during the seventh week after transplant (median day
      40, range 26-58) at about the time of symptom onset. Mean viral titer measured
      during the seventh week was 1.2 x 10(5) copies per milliliter of serum (standard
      error 6.5 x 10(4). Buffy-coat PCR results were generally concordant with results
      of serum PCR (overall concordance 103/133=77.4%). Serum CMV titer fell, as
      symptoms resolved with reduction of immunosuppression and specific antiviral
      therapy. High titers and poor response to antiviral therapy were observed in the
      context of excessive immunosuppression and bacterial sepsis. Measurement of serum
      CMV titer may be useful for the management of immunosuppressed transplant
      recipients, and provides a tool for the better understanding of factors that
      enhance or inhibit viral replication.

PMID- 9000664
TI  - Secretion and composition of bile after human liver transplantation: studies on
      the effects of cyclosporine and tacrolimus.
AB  - Cyclosporine (CsA) and tacrolimus (FK506) have recently been reported to inhibit
      canalicular transport of bile acids in vitro and thereby possibly induce
      cholestasis. A relative reduction of chenodeoxycholic acid (CDCA) has been
      observed after liver transplantation when CsA is used as immunosuppressant. We
      tested the hypothesis that CsA induces cholestasis and reduces CDCA secretion as
      compared with treatment with monoclonal antibodies (OKT3), and that CsA differs
      from FK506 with regard to its effects on biliary lipid secretion. Bile flow,
      biliary lipid secretion rates, and biliary bile acid composition were determined
      during the first 10 days after transplantation in 29 liver transplant recipients.
      Two prospective randomized studies were performed that compared CsA and OKT3 and
      compared CsA- and FK506-based regimens. In study 1, bile acid output averaged
      0.75+/-0.15 micromol/min in the CsA I group and 0.54+/-0.11 micromol/min in the
      OKT3 group on postoperative day 1. Bile flow and bile acid output then increased,
      and there was no significant difference between the two groups. The relative
      proportion of CDCA decreased to the same extent in both groups. In study 2, mean
      bile acid outputs on postoperative day 1 were 0.57+/-0.26 micromol/min and 0.55+/
      0.15 micromol/min in the CsA 2 and FK506 groups, respectively. The following
      increase in bile acid secretion was significantly larger in the FK506 group.
      After transplantation, the relative proportion of CDCA decreased with time in
      both groups, but the reduction was more rapid in the FK506 group. In conclusion,
      CsA did not inhibit bile secretion during short-term treatment after liver
      transplantation. Compared with patients given CsA-based treatment, patients with
      FK506-based treatment recovered bile secretion more rapidly.

PMID- 9000665
TI  - Donor origin of a posttransplant liver allograft malignancy identified by
      fluorescence in situ hybridization for the Y chromosome and DNA genotyping.
AB  - Posttransplantation malignancy in the allograft is a rare complication of
      orthotopic liver transplantation. In the described case, an abnormal T-tube
      cholangiogram, performed 6 months after orthotopic liver transplantation between
      a male donor and a female recipient, prompted needle liver biopsy. A moderately
      differentiated adenocarcinoma was found. Fluorescence in situ hybridization for
      the Y chromosome indicated male origin of malignancy. Donor-related disease was
      confirmed by comparative DNA analysis of genomic sequences from the donor liver,
      associated tumor, and recipient peripheral blood. Results of these investigations
      qualified the recipient for a second liver transplant.

PMID- 9000666
TI  - Significance of preformed anti-donor antibodies in liver transplantation.
AB  - The significance of a positive cross-match in liver transplantation remains
      controversial, as documented by a number of recent conflicting reports. In this
      study, we evaluated 195 consecutive orthotopic liver transplant recipients in
      whom the cross-match was either negative or positive for T or B cells. Special
      emphasis was placed on the outcome of patients with high levels of preformed IgG
      antibodies directed against donor T cells. IgG anti-donor antibodies were
      confirmed by flow cytometry in all cases. Of 10 patients with strong T-cell
      antibodies, there was one early death due to nonimmunological causes.
      Transplantation was successful in 9/10 patients followed for 3 months to 3 years.
      Graft survival, incidence of acute rejection, and number of liver biopsies in
      patients with a positive cross-match (strong T, weak T, or B cell) were not
      significantly different from those of patients with a negative cross-match. In
      the strong T cell antibody group, one patient had early graft dysfunction, with
      extensive hepatic necrosis and histological signs of antibody-induced damage. Two
      other patients also showed some evidence of possible antibody-mediated events,
      such as neutrophil infiltration and hepatocyte swelling. These lesions were
      reversible, and the patients had uneventful recoveries. Thus, in our experience,
      preformed antibodies did not preclude good graft survival.

PMID- 9000667
TI  - Glutathione S-transferase as predictor of functional outcome in transplantation
      of machine-preserved non-heart-beating donor kidneys.
AB  - Non-heart-beating (NHB) donors are a valuable source of kidneys for
      transplantation. The organs, however, sustain substantial warm ischemic damage
      that may jeopardize the transplantability and result in nonfunction of the
      grafts. Quantification of warm ischemic time (WIT) and prediction of transplant
      outcome are essential for the use of NHB donor organs. During machine
      preservation (MP) the viability of NHB donor kidneys was evaluated through
      calculating intrarenal vascular resistance and determining lactate dehydrogenase
      and alpha-glutathione S-transferase (alphaGST) in the perfusate. Thirty-seven
      functioning (F) and nine nonfunctioning kidneys (NF) were compared. WIT was
      longer in NF; serum creatinine, donor age, and preservation time were not
      different. WIT correlated well with alphaGST after 4 and 8 hr of MP (r=0.353,
      P=0.009, and r=0.346, P=0.011, respectively). When compared with F, intrarenal
      vascular resistance was increased in NF after 4 and 8 hr of perfusion (P<0.05);
      at all time points, alphaGST levels were elevated in NF (P<0.05). Lactate
      dehydrogenase activity was not different between the groups, but could identify
      immediate functioning grafts within the F group. In conclusion, alphaGST levels
      correlated strongly with WIT and were also able to distinguish NF from F grafts.
      alphaGST can adequately predict the functional outcome of NHB donor grafts before
      transplantation; levels of alphaGST can be used to define reliable safety margins
      for viability. Therefore, MP is useful in evaluating the viability of NHB donor
      kidneys, and the parameters discussed will help to select nonviable grafts from
      this valuable pool of kidneys for transplantation.

PMID- 9000668
TI  - Attenuation of lethal graft-versus-host disease by inhibition of nitric oxide
      synthase.
AB  - We have previously demonstrated that administration of the nitric oxide (NO)
      synthesis inhibitor aminoguanidine (AG) to mice undergoing nonlethal graft-versus
      host disease (GVHD) results in less destruction of host tissue and enhanced
      proliferative responses of splenic lymphocytes. Subsequently, we have determined
      whether the amelioration of GVHD pathology associated with inhibition of NO
      synthesis affects survival in a lethal GVHD model. Utilizing a C57BL/6 to
      C57BL/6xDBA2JF1 model, administration of parental lymph node lymphocytes instead
      of splenocytes results in 80-90% lethality by week 4 after GVHD induction.
      Administration of AG resulted in significantly decreased lethality coincident
      with decreased serum NO2- + NO3- levels. AG therapy had no effect on donor anti
      host cytolytic T cell activity, which indicates that destruction of host tissue
      via this pathway was unaffected by the therapy. Histological evaluation of
      spleen, small intestine, bone, and mesenteric lymph node did not reveal any
      difference in the histological correlates of disease in the treated mice. AG
      increased various hematopoietic indices, including red blood cell count, white
      blood cell count, and hemoglobin, which indicates that the disruption of
      hematopoiesis during acute GVHD is mediated in part by NO. In addition, the
      number of GVHD mice with endogenous bacterial infections in the spleen and liver
      was significantly decreased in mice receiving AG therapy. These data indicate
      that NO plays a detrimental role during GVHD that appears to result in decreased
      hematopoietic indices and concomitant susceptibility to bacterial infection.

PMID- 9000669
TI  - Apoptotic cell death in human chronic renal allograft rejection.
AB  - Chronic renal allograft rejection is characterized by gradual progression
      suggesting persistent low-grade injury. Apoptotic cell death may be initiated by
      low-grade injury secondary to external factors, making apoptosis a potential
      pathway of chronic rejection. In the present investigation, protocol kidney
      biopsies of 20 pediatric renal allograft recipients (12 with chronic rejection
      and 8 with normal histology), 9 pediatric liver allograft recipients, and 7
      children with minimal change nephrotic syndrome were evaluated. The presence of
      apoptotic cell death was studied by determining apoptosis-induced
      oligonucleosomal DNA fragmentation in the biopsy specimens using 3' end labeling
      with terminal transferase, gel fractionation, and Southern blotting. The specific
      cell types with increased DNA fragmentation were determined by in situ 3' end
      labeling performed on sections of the biopsies. Significant DNA fragmentation was
      found only in the specimens from patients with chronic rejection. In situ
      investigation revealed increased apoptosis of both proximal and distal tubular
      epithelial cells, but not in the glomeruli or interstitium. The mean number of
      apoptotic tubular epithelial cells per 400x magnified field was higher in the
      renal allografts than in kidneys of liver transplant recipients or patients with
      minimal change nephrotic syndrome (2.3 vs. 0.8, P<0.05, in both cases). Our data
      provide biochemical evidence of increased apoptotic cell death of renal tubular
      epithelial cells in patients undergoing chronic renal allograft rejection.

PMID- 9000670
TI  - Role of polymorphic Fc receptor Fc gammaRIIa in cytokine release and adverse
      effects of murine IgG1 anti-CD3/T cell receptor antibody (WT31).
AB  - Anti-CD3 monoclonal antibody (mAb) OKT3 is immunosuppressive, but causes severe
      adverse effects during the first administration ("first-dose reaction"). These
      adverse effects are presumably caused by cytokine release that results from T
      cell activation. In vitro, T-cell activation by anti-CD3 mAb requires interaction
      with monocyte Fc receptors. The Fc receptor for murine IgG1, Fc gammaRIIa, is
      polymorphic. In some individuals, murine IgG1 anti-CD3 mAb causes T-cell
      proliferation and cytokine release in vitro (high responders [HR]), whereas in
      individuals with the low-responder (LR) phenotype it does not. We have now
      investigated the role of this Fc gammaRIIa polymorphism in the release of
      cytokines in vivo and the occurrence of adverse effects after the administration
      of WT31, a murine IgG1 anti-CD3/T cell receptor mAb. WT31 caused an increase of
      plasma tumor necrosis factor-alpha in all four HR patients and none of the five
      LR patients. In all HR patients except one, plasma gamma-interferon and
      interleukin 6 also increased, and a first-dose response was observed, whereas no
      cytokine release or adverse effects occurred in any of the LR patients. WT31
      caused lymphopenia in all HR and none of the LR patients. FACS analysis
      demonstrated that in HR patients, after the initial disappearance of CD3+ cells
      from peripheral blood, modulation of CD3 occurred, whereas in LR patients a high
      degree of coating of the lymphocytes was observed. Surprisingly, WT31 also
      induced a marked granulocytopenia, as well as a decrease of thrombocytes, in
      three of the four HR patients (and in none of the LR patients). These data
      provide direct clinical evidence that Fc receptor interaction determines the
      release of cytokines and the occurrence of adverse effects after administration
      of anti-CD3/T cell receptor mAb. Furthermore, these data suggest that tumor
      necrosis factor-alpha by itself is not sufficient to induce the first-dose
      reaction.

PMID- 9000671
TI  - Lack of cognate help by CD4+ T cells and anergy of CD8+ T cells are the principal
      mechanisms for anti-leukocyte function-associated antigen-1/intercellular
      adhesion molecule-1-induced cardiac allograft tolerance.
AB  - Combined treatment with anti-leukocyte function-associated antigen-1 (LFA-1) and
      anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibodies leads to
      allograft tolerance in murine cardiac transplantation. In the present study, we
      analyzed the mechanisms for this tolerance induction. In the tolerant mice,
      proliferative response of splenic T cells against donor-type cardiac myocytes and
      of CD8+ T cells against donor-type alloantigens was impaired as compared with
      responses in naive or rejected mice, but was completely restored with exogenous
      interleukin 2. This suggests that class I-restricted CD8+ T cells of tolerant
      mice were rendered anergic against donor-type alloantigens in the periphery. In
      contrast, proliferative response of CD4+ T cells against donor-type alloantigens
      in vitro was comparable between tolerant and naive mice. When heart and skin
      grafts from the same donor (BALB/c [H2d]) were simultaneously transplanted to C3H
      mice (H2k), both were rejected within 29 days, even though the mice were
      similarly treated with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies. In
      contrast, when heart graft from BALB/c and skin graft from third-party donor
      (C57BL/6 [H2b]) were simultaneously transplanted to C3H mice under the same
      condition, the heart graft was accepted indefinitely and the skin graft was
      rejected. These findings suggest that the peripheral tolerance against cardiac
      allografts could be induced by selective inactivation of alloreactive CD8+ T
      cells resulting from the lack of cognate help by CD4+ T cells.

PMID- 9000672
TI  - Major histocompatibility complex class I-independent killing of xenogeneic
      targets by rat allospecific natural killer cells.
AB  - Major histocompatibility complex class I molecules can inhibit mouse as well as
      human natural killer (NK) cell cytotoxicity. In contrast, antigens encoded in the
      RT1.C region of the rat MHC gene complex have been suggested to trigger, rather
      than inhibit, rat NK cells. In an attempt to analyze rat NK cell specificity,
      with respect to the cross-species difference that may exist in NK cell-mediated
      cytotoxicity, we investigated the ability of interleukin 2-activated,
      allospecific rat NK cells to recognize MHC class I-positive and -deficient target
      cells of mouse and human origins. Recognition of xenogeneic target cells by rat
      allospecific NK cells was found to be MHC class I independent; target cell MHC
      class I was not required for killing, and expression of different sets of mouse
      and human MHC class I molecules did not influence the cytotoxic response. These
      results indicate that rat NK cells can recognize xenogeneic nontransformed cells
      by mechanisms not related to target cell MHC class I expression, and that mouse
      and human MHC class I molecules, at least among those tested in this study, are
      unable to confer inhibition of rat NK cells.

PMID- 9000673
TI  - Discordant xenogeneic neonatal thymic transplantation can induce donor-specific
      tolerance.
AB  - The limited supply of human organs for transplantation necessitates the
      development of methods leading to acceptance of xenografts. To avoid the hazards
      of the high-dose chronic immunosuppressive pharmacotherapy which would otherwise
      be required for successful xenografting, it would be desirable to induce
      permanent tolerance to xenogeneic donors. We have recently demonstrated that
      xenogeneic donor-specific tolerance can be induced by transplanting fetal pig
      thymic and hematopoietic tissue into thymectomized, T cell-depleted, and natural
      killer-cell-depleted mice, or into natural killer cell-depleted nude mice. We
      have now extended these studies by replacing fetal tissue with neonatal pig
      thymic and hematopoietic tissue, and by examining the in vivo responses of
      reconstituted mice to pig skin grafts. Neonatal tissue was studied because it
      might be more practicable than fetal tissue for the purpose of transplantation to
      primates. BALB/c nu/nu mice transplanted with neonatal (<24-hr-old) pig thymus
      and spleen fragments developed circulating mouse CD4+ cells. The pig thymus
      grafts were necessary for mouse T-cell development, as CD4 recovery did not occur
      in recipients of neonatal pig splenic tissue alone. The CD4+ cells that developed
      included Vbeta8.1/2+ T cells in similar proportions as in BALB/c mice, and
      Vbeta11+ and Vbeta5+ CD4 T cells were deleted almost as completely as in normal
      BALB/c mice. This deletion was detected among CD4 single-positive graft
      thymocytes. In 9 of 12 evaluable animals, mixed lymphocyte responses demonstrated
      tolerance to donor-type pig SLA antigens, with responsiveness to alloantigens
      and/or third-party pig xenoantigens. Furthermore, grafting of neonatal pig thymus
      conferred the ability to reject allogeneic mouse skin in 7 of 10 animals. In
      addition, 7 of 10 animals accepted paternal (donor SLA-matched) skin (median
      survival time [MST] > 100 days), whereas 4 of 4 animals rejected third-party SLA
      mismatched pig skin (MST=40.5 days). We conclude that neonatal pig thymi
      transplanted to BALB/c nu/nu mice can support the development of mouse CD4+ cells
      that are functional and specifically tolerant to donor-type pig antigens.

PMID- 9000674
TI  - Enhancement of proliferation of intrasplenically transplanted hepatocytes in
      cirrhotic rats by hepatic stimulatory substance.
AB  - This study aimed at investigating the efficacy of hepatic stimulatory substance
      (HSS) on the proliferation of transplanted hepatocytes in the spleen of rats with
      carbon tetrachloride (CCl4)-induced liver cirrhosis. After hepatocyte
      transplantation (HTx; 1x10(7) cells/rat), the recipients received intravenous
      administration of HSS (3ml) of 2, 4, or 7 times/week to investigate the effect of
      the frequency of HSS treatment on the proliferation of intrasplenically
      transplanted hepatocytes. Next, to investigate the effect of the severity of
      liver cirrhosis on HSS-stimulated proliferation of transplanted hepatocytes,
      different doses (0.00, 0.08, 0.12, and 0.16 ml/week) of CCl4 were given to rats
      after HTx. The recipients were killed and the spleens were removed at 2 and 4
      weeks after HTx and stained with bromodeoxyuridine (BrdU) and hematoxylin and
      eosin for determining the BrdU labeling index (L.I.) and the hepatocyte-occupied
      area ratio in the longitudinal cut surface of the spleen (H:S ratio),
      respectively. The H:S ratio was measured in the hematoxylin and eosin-stained
      splenic sections under a light microscope connected to an image processor. HSS
      treated rats showed significantly higher BrdU L.I. and H:S ratios than the
      untreated control rats at 2 and 4 weeks after HTx. However, the difference in the
      BrdU L.I. and H:S ratio was not statistically significant among the HSS-treated
      rats. Without HSS treatment, the severity of liver cirrhosis did not affect the
      proliferation of intrasplenically transplanted hepatocytes. On the other hand,
      HSS-induced proliferation of transplanted hepatocytes was further enhanced in
      proportion to the severity of liver cirrhosis. The H:S ratio of the rats treated
      with 0.04, 0.08, and 0.16 ml/week of CCl4 after HTx was 1.27+/-0.5%, 4.32+/
      0.65%, and 6.25+/-0.70%, respectively, at week 4. During the long-term
      observation of up to 12 weeks, a marked decrease in the H:S ratio was observed in
      HSS-untreated control rats at weeks 4-12 compared with week 2. While HSS-treated
      rats revealed gradual proliferation of intrasplenically transplanted hepatocytes,
      the difference in the H:S ratio between HSS-treated and -untreated rats became
      larger. These results indicate that HSS treatment of recipient rats stimulated
      the proliferation of intrasplenically transplanted hepatocytes in cirrhotic rats
      and that the severity of liver cirrhosis enhanced the stimulative effect of HSS
      on the proliferation of transplanted hepatocytes.

PMID- 9000675
TI  - Respiratory defect as an early event in preservation-reoxygenation injury of
      endothelial cells.
AB  - Characterization of preservation injury in endothelial cells has been primarily
      accomplished by measurement of cell viability. To analyze early events and
      cellular mechanisms of preservation-reoxygenation injury, we developed high
      resolution respirometry for the study of mitochondrial function in endothelial
      cells, to provide a quantitative marker for sublethal stress. Cultured human
      umbilical vein endothelial cells were stored for 4 and 8 hr at 4 degrees C under
      an atmosphere of 95% N2 and 5% CO2 in University of Wisconsin (UW) and histidine
      tryptophan-ketoglutarate (HTK) solutions. Respiration of suspended cells,
      measured after reoxygenation in growth medium at 37 degrees C, was significantly
      reduced in all treatments in comparison to controls not subjected to cold
      preservation. In contrast, trypan blue staining was unchanged after 4 hr of
      preservation and was significant only after 8 hr. After 8 hr of cold storage in
      UW and HTK solutions, respiration was 64+/-5% and 49+/-6%, respectively, of
      controls (46.5+/-3.3 pmol O2 x s(-1 x 10(-6) cells), indicating significantly
      better protection by UW solution than HTK solution. A titration regimen with
      substrate (succinate), uncoupler (carbonyl cyanide p
      trifluoromethoxyphenylhydrazone), and inhibitors of complexes I and III (rotenone
      and antimycin A) resulted in identical respiratory response patterns in all
      treatments. The plasma membrane remained impermeable to succinate. Inner
      mitochondrial membrane function was preserved as indicated by a constant relative
      increase of respiration after uncoupling. These results demonstrate that loss of
      catalytic capacity for respiration constitutes an early event in preservation
      reoxygenation injury, whereas membrane damage is not a primary defect.
      Respirometric evaluation of sublethal cell injury and localization of cell damage
      may provide selective guidelines for further optimization of strategies in organ
      preservation.

PMID- 9000676
TI  - Interleukin 1 receptor blockade reduces tumor necrosis factor production, tissue
      injury, and mortality after hepatic ischemia-reperfusion in the rat.
AB  - The inflammatory cytokines interleukin (IL) 1 and tumor necrosis factor (TNF) may
      play an important role in hepatic ischemia-reperfusion (I/R) injury. To study the
      role of IL-1 in hepatic I-R injury, we investigated the effect of pretreatment
      with IL-1 receptor antagonist (IL-1ra) on the production of IL-1, TNF,
      histological findings in the liver, and the survival rate for 7 days. Rats were
      subjected to 90 min of partial liver warm ischemia by clamping the vessels of the
      left and middle lobes. In the IL-1ra-treated group, IL-1ra was given 5 min before
      liver ischemia was induced. IL-1alpha and TNF levels were determined in blood and
      liver at 0, 30, 90, and 180 min after reperfusion. In a second experiment to
      determine the effect of IL-1ra pretreatment on survival rate, after 90 min of
      partial liver ischemia, the right lateral and caudate lobes were excised, leaving
      only the ischemic lobes. In both groups, IL-1alpha was undetectable in blood, but
      increased in liver tissue. TNF increased in both blood and liver tissue as
      reperfusion time increased. Histological evidence of tissue injury was minimal in
      the IL-1ra-treated group. Furthermore, in the IL-1ra-treated group, the
      production of TNF decreased in both blood and liver tissue compared with the
      nontreated group. Survival rates in the IL-1ra-treated and nontreated group were
      80% and 30%, respectively. The data demonstrated that the production of IL-1 and
      TNF increases in hepatic I-R injury and that pretreatment with IL-1ra protects
      the liver from ischemic insult, indicating an important role for IL-1 in I-R
      injury.

PMID- 9000677
TI  - Transgenic pigs expressing human CD59 and decay-accelerating factor produce an
      intrinsic barrier to complement-mediated damage.
AB  - We characterize a line of transgenic pigs that express the human complement
      regulatory proteins human CD59 and human decay-accelerating factor. These genes,
      under the control of heterologous promoters, are expressed in a variety of
      organs, including the vasculature of the heart, kidney, and liver. We demonstrate
      that moderate levels of these gene products are sufficient to protect peripheral
      blood cells from human or baboon complement. Using pig to baboon heterotopic
      heart transplants, we show that expression of these proteins is sufficient to
      block the complement-mediated damage that is the hallmark of such xenografts,
      when nontransgenic organs are used. These results indicate that there is
      significant species specificity of intrinsic complement regulatory protein
      function. This specificity is evident in transgenic organs in which low levels of
      human CD59 and human decay-accelerating factor expression significantly effect
      the humoral immune response that causes xenograft rejection. This result suggests
      that transgenic organs with high levels of human complement-regulatory protein
      expression will be sufficient to alleviate the humoral immunological barriers
      that currently block the use of xenogeneic organs for human transplantation.

PMID- 9000678
TI  - alpha-smooth muscle actin and collagen deposition in dysfunctional renal
      transplants.
AB  - In normal kidneys, alpha-smooth muscle actin and collagen type III expression is
      restricted to vascular smooth muscle cells and perivascular fibrous tissues,
      respectively, but in pathological conditions their expression or deposition is
      more extensive. Using immunohistochemistry, we examined the expression of alpha
      smooth muscle actin and type III collagen in 31 human renal transplant biopsy
      specimens obtained from patients with graft dysfunction. We found that
      dysfunctional renal transplants have increased alpha-smooth muscle actin and
      collagen III expression in the glomerulus and interstitium, but only glomerular
      alpha-smooth muscle actin expression correlates with graft function and
      prognosis.

PMID- 9000679
TI  - Hepatitis C virus-related fibrosing cholestatic hepatitis after renal
      transplantation.
AB  - Fibrosing cholestatic hepatitis is a well-described syndrome in patients with
      immunodeficiency and chronic hepatitis B. It is clinically, biologically, and
      histologically characterized by rapidly progressive hepatic failure, a mildly
      elevated serum aminotransferase level, an extensive periportal fibrosis
      associated with intense cholestasis, mild inflammatory cellular infiltrate, no
      cirrhosis, and a high hepatocellular level expression of B viral antigens. This
      syndrome reflected a direct hepatocytopathic injury linked to high intrahepatic
      viral antigen expression. Because the syndrome of fibrosing cholestatic hepatitis
      has not been described in chronic hepatitis C, we report the first well
      characterized case in a renal transplant patient with chronic hepatitis C and
      discuss the clinical and pathogenic implications of such a syndrome in this
      setting.

PMID- 9000681
TI  - Lower extremity paralysis after use of the supraceliac aorta for hepatic arterial
      reconstruction of the transplanted liver.
AB  - Use of the supraceliac aorta for hepatic arterial reconstruction of the
      transplanted liver in the setting of inadequate recipient celiac and hepatic
      arterial inflow has been advocated and has resulted in a decreased hepatic artery
      thrombosis rate in both the adult and pediatric populations. Over the past 6
      years, we have utilized the supraceliac aorta in more than 200 patients without
      complication. However, in this communication, we report a major neurologic
      complication that resulted in anterior spinal artery syndrome.

PMID- 9000680
TI  - Multiple Cladosporium brain abscesses in a renal transplant patient: aggressive
      management improves outcome.
AB  - Infection remains one of the major complications of nonspecific immunosuppression
      in renal transplant patients and accounts for significant morbidity and
      mortality. The incidence of infectious complications has been shown to be related
      to the degree of immunosuppression and correlated with the total steroid dosage,
      use of antilymphocyte serum, and number of rejection episodes. We present the
      case of a patient who received a large cumulative immunosuppressive load as
      treatment for her original disease and for numerous rejection episodes following
      renal transplantation, and who later developed multiple brain abscesses. These
      were shown to be due to the saprophytic black fungus Cladosporium bantianum. This
      case emphasizes the importance of aggressively pursuing the diagnosis in
      immunosuppressed individuals--appropriate treatment may be instituted early and
      may save lives. There have been no previous cases of patients surviving this
      condition without neurosurgical resection of the lesions.

PMID- 9000682
TI  - Cyclosporine and pregnancy in the rat.
AB  - Female Wistar rats mated with male Wistar rats were given 15 mg/kg cyclosporine
      (CsA) per day during pregnancy (to 21 days after coitus). Other rats were mated
      and were used as controls. The pups born from treated mothers were fed by control
      mothers and those born from control mothers were fed by treated mothers. The
      newborn rats showed temporary defects in the development of some hemopoietic
      organs (the thymus, spleen, liver, and bone marrow). There was no difference in
      the structure of the organs studied between the litters fed by control mothers
      and those fed by treated mothers. The structure of the hemopoietic organs
      resembled those of the controls 30 days after birth. Our findings show that the
      delay in the development of the organs studied is due to the transplacental
      passage of CsA and suggest that it could be due to CsA interference in the
      maternal immune response to specific embryonic antigens.

PMID- 9000684
TI  - The synergistic effects of cyclosporine and sirolimus.

PMID- 9000683
TI  - The presence of posttransplant HLA-specific IgG antibodies detected by enzyme
      linked immunosorbent assay correlates with specific rejection pathologies.
AB  - Posttransplant monitoring of anti-HLA antibodies with routine techniques gives
      unsatisfactory results due to a variety of technical limitations. We investigated
      how a new alternative technique correlates with posttransplant clinical events. A
      total of 313 nonselected serum samples from 136 patients were screened by an
      ELISA utilizing captured soluble HLA class I antigens. We observed the absence of
      anti-HLA antibody production in acute rejection cases responding to standard
      antirejection therapy. On the other hand, we showed a clear presence of these
      antibodies in acute rejection episodes not responding to standard therapy
      (P<0.0001) and in chronic rejection (P<0.001). We conclude that routine
      posttransplant monitoring by ELISA offers early risk assessment that is crucial
      for proper immunosuppression and for antirejection therapy choice.

PMID- 9000685
TI  - OKT3 and hepatitis C: defining the risks.

PMID- 9000686
TI  - Ciprofloxacin does not block the antiproliferative effect of tacrolimus.

PMID- 9000687
TI  - Mycophenolate Mofetil Study.

PMID- 9000688
TI  - Acute graft rejection after treatment with human growth hormone.

PMID- 9000689
TI  - Gradients for rat islet separation.

PMID- 9000690
TI  - The role of enteroviral infections in the development of IDDM: limitations of
      current approaches.
AB  - Enteroviruses have been examined for their possible role in the etiology of IDDM
      for nearly 40 years, yet the evidence remains inconclusive. The mechanism of
      acute cytolytic infection of beta-cells, proposed by earlier studies, appears to
      be incompatible with the long preclinical period of autoimmunity preceding IDDM.
      Advances in molecular biology have improved our understanding of enteroviral
      biology and of potential alternative pathogenic mechanisms through which
      enteroviruses may cause diabetes. The focus of future human studies will likely
      shift from people with IDDM to those with prediabetic autoimmunity to determine
      whether acute enteroviral infections can promote progression from autoimmunity to
      overt diabetes. We propose that such studies use assays to detect enteroviral
      RNA, in addition to IgM serology. RNA assays can overcome sensitivity and type
      specificity limitations of IgM assays as well as identify diabetogenic strains of
      enteroviruses, if such exist. Evaluation of the role of enteroviruses in
      triggering beta-cell autoimmunity in humans will require large prospective
      studies of young children. The Diabetes Autoimmunity Study in the Young--one of
      very few such studies currently underway--is focusing on potential interactions
      between HLA class II genes and enteroviral infections. Future studies will likely
      examine interactions between viral infections and non-HLA IDDM candidate genes,
      including those that may determine beta-cell tropism of candidate viruses.

PMID- 9000691
TI  - Alterations in the expression and cellular localization of protein kinase C
      isozymes epsilon and theta are associated with insulin resistance in skeletal
      muscle of the high-fat-fed rat.
AB  - We have tested the hypothesis that changes in the levels and cellular location of
      protein kinase C (PKC) isozymes might be associated with the development of
      insulin resistance in skeletal muscles from the high-fat-fed rat. Lipid
      measurements showed that triglyceride and diacylglycerol, an activator of PKC,
      were elevated four- and twofold, respectively. PKC activity assays indicated that
      the proportion of membrane-associated calcium-independent PKC was also increased.
      As determined by immunoblotting, total (particulate plus cytosolic) PKC alpha,
      epsilon, and zeta levels were not different between control and fat-fed rats.
      However, the ratio of particulate to cytosolic PKC epsilon in red muscles from
      fat-fed rats was increased nearly sixfold, suggesting chronic activation. In
      contrast, the amount of cytosolic PKC theta was downregulated to 45% of control,
      while the ratio of particulate to cytosolic levels increased, suggesting a
      combination of chronic activation and downregulation. Interestingly, while
      insulin infusion in glucose-clamped rats increased the proportion of PKC theta in
      the particulate fraction of red muscle, this was potentiated by fat-feeding,
      suggesting that the translocation is a consequence of altered lipid flux rather
      than a proximal event in insulin signaling. PKC epsilon and theta measurements
      from individual rats correlated with triglyceride content of red gastrocnemius
      muscle; they did not correlate with plasma glucose, which was not elevated in fat
      fed rats, suggesting that they were not simply a consequence of hyperglycemia.
      Our results suggest that these specific alterations in PKC epsilon and PKC theta
      might contribute to the link between increased lipid availability and muscle
      insulin resistance previously described using high-fat-fed rats.

PMID- 9000692
TI  - Glucokinase regulatory protein may interact with glucokinase in the hepatocyte
      nucleus.
AB  - Glucokinase (GK) plays a central role in the sensing of glucose in pancreatic
      beta-cells and parenchymal cells of the liver. Glucokinase regulatory protein is
      a physiological inhibitor of GK in the liver. To understand the role of the
      interaction of these two proteins in glucose sensing, we carried out a series of
      experiments to localize the protein in the liver cell. The regulatory protein was
      found to be present mainly in the nucleus of the cell under a variety of
      conditions that mimicked the glucose status of the fed and fasted state. GK was
      localized in the nucleus when the cells were exposed to low glucose
      concentrations. At higher glucose concentrations or in the presence of low
      concentrations of fructose, GK translocated to the cytoplasm. The effect of
      fructose was more robust and rapid than the effect of high glucose
      concentrations. Furthermore, the effect of fructose and high glucose on the
      translocation of GK from the nucleus could be partially reversed by glucagon.
      This unusual localization and behavior suggests a role for GK and its regulatory
      protein in hepatic energy metabolism that may be broader than glucose
      phosphorylation.

PMID- 9000693
TI  - The role of fatty acids in mediating the effects of peripheral insulin on hepatic
      glucose production in the conscious dog.
AB  - We investigated the mechanism by which a selective increase in arterial insulin
      can suppress hepatic glucose production in vivo. Isotopic (3-3H-glucose) and
      arteriovenous difference methods were used in overnight-fasted, conscious dogs. A
      pancreatic clamp (somatostatin, basal portal insulin, and glucagon infusions) was
      used to control the endocrine pancreas. Equilibration (100 min) and basal (40
      min) periods were followed by a 180-min test period. In control dogs (n = 5),
      basal insulin delivery was continued throughout the study. In the other two
      groups, peripheral insulin was selectively increased at the beginning of the test
      period by stopping the portal insulin infusion and infusing insulin peripherally
      at twice the basal portal rate. One group (INS + FAT; n = 6) received an infusion
      of 20% intralipid + heparin (0.5 U x kg(-1) x min(-1)) to clamp the nonesterified
      fatty acid (NEFA) levels during hyperinsulinemia; the other group (INS; n = 7)
      received only saline during the experimental period. In the INS group, a
      selective increase in peripheral insulin of 84 pmol/l was achieved (36 +/- 6 to
      120 +/- 24 pmol/l, last 30 min) while portal insulin was unaltered (84 +/- 18
      pmol/l). In the INS + FAT group, a similar increase in peripheral insulin was
      achieved (36 +/- 6 to 114 +/- 6 pmol/l, last 30 min); again, portal insulin was
      unaltered (96 +/- 12 pmol/l). In the control group, basal insulin did not change.
      Glucagon and glucose remained near basal values in all protocols. In the INS
      group, NEFA levels dropped from 700 +/- 90 (basal) to 230 +/- 65 micromol/l (last
      30 min; P > 0.05), but in the INS + FAT group changed minimally (723 +/- 115
      [basal] to 782 +/- 125 micromol/l [last 30 min]). In the INS group, net hepatic
      glucose output dropped by 6.7 micromol x kg(-1) x min(-1) (P < 0.05), whereas in
      the INS + FAT group it dropped by 3.9 micromol x kg(-1) x min(-1) (P < 0.05).
      When insulin levels were not increased (i.e., in the control group), net hepatic
      glucose output dropped 1.7 micromol x kg(-1) x min(-1) (P < 0.05). In all groups,
      the net hepatic glucose output data were confirmed by the tracer-determined
      glucose production data. In the INS group, net hepatic gluconeogenic substrate
      uptake (alanine, glutamine, glutamate, glycerol, glycine, lactate, threonine, and
      serine) fell slightly (10.4 +/- 1.3 [basal] to 7.2 +/- 1.3 micromol x kg(-1) x
      min(-1) [last 30 min]), whereas in the INS + FAT group it did not change (7.3 +/-
      1.5 [basal] to 7.4 +/- 0.6 micromol x kg(-1) x min(-1) [last 30 min]), and in the
      control group it increased slightly (9.6 +/- 1.3 [basal] to 10.3 +/- 1.4 micromol
      x kg(-1) x min(-1) [last 30 min). These results indicate that peripheral
      insulin's ability to regulate hepatic glucose production is partially linked to
      its inhibition of lipolysis. When plasma NEFA levels were prevented from falling
      during a selective arterial hyperinsulinemia, approximately 55% of insulin's
      inhibition of net hepatic glucose output (NHGO) was eliminated. The fall in NEFA
      levels brings about a redirection of glycogenolytically derived carbon within the
      hepatocyte such that there is an increase in lactate efflux and a corresponding
      decrease in NHGO.

PMID- 9000694
TI  - Characterization of the insulin inhibition of the peptidolytic activities of the
      insulin-degrading enzyme-proteasome complex.
AB  - Insulin-degrading enzyme (IDE) is a component of a cytosolic complex that
      includes multicatalytic proteinase (MCP), the major cytoplasmic proteolytic
      activity. Insulin, the primary substrate for IDE, inhibits the proteolytic
      activity of the IDE-MCP complex but not of purified MCP. This provides a
      regulatory role for IDE in cellular proteolysis and a potential mechanism for
      intracellular insulin action. To examine the specificity and to explore the
      mechanisms for the IDE-MCP interaction, we studied the functional interaction of
      a variety of peptides with the complex. Atrial natriuretic peptide (ANP),
      relaxin, glucagon, proinsulin, and insulin-like growth factor II (IGF-II) bind to
      and are degraded by IDE. These peptides have significant inhibitory effects on
      the chymotrypsin-like and trypsin-like MCP catalytic activities but not the
      peptidyl-glutamyl hydrolyzing activity. A panel of peptides that are not ligands
      of IDE had no effect. To explore the potential mechanism for the IDE control of
      MCP activity, dose response curves for insulin-like growth factor I (IGF-I) and
      IGF-II effects on MCP chymotrypsin-like activity were determined. IGF-II, which
      (similar to insulin) is a good substrate for IDE, had a substantial inhibitory
      effect, whereas IGF-I, which is bound but poorly degraded, had little inhibitory
      activity on MCP. Proinsulin, another ligand of IDE that is tightly bound but
      poorly degraded, had a partial effect on MCP activity, but inhibited the full
      insulin effect. These data suggest a requirement for both the binding and
      degradation of IDE ligands for the full inhibition of MCP. Insulin-sized
      degradation products, substrates of IDE, also inhibited MCP activity. Further
      examination of the insulin effect on MCP included kinetic studies. Insulin
      produced a noncompetitive inhibition of both the chymotrypsin-like and trypsin
      like activities of MCP. These data suggest that the insulin-IDE effect on MCP is
      due to conformational changes in the IDE-MCP complex and provide an intracellular
      mechanism of action for insulin.

PMID- 9000695
TI  - Abnormal regulation of hepatic glucose output in maturity-onset diabetes of the
      young caused by a specific mutation of the glucokinase gene.
AB  - A subtype of maturity-onset diabetes of the young (MODY) is caused by mutations
      of the glucokinase gene, an enzyme expressed in pancreatic beta-cells and the
      liver. To assess the consequences of a functional alteration of glucokinase at
      the level of the liver, endogenous (hepatic) glucose production and glucose
      cycling (an indirect assessment of hepatic glucokinase activity) were measured
      with 2-2H glucose and 6,6-2H glucose in patients who developed MODY because of
      the V203A mutation of glucokinase, and in control subjects at similar levels of
      glycemia. Measurements were performed in the postabsorptive state and after
      ingestion of 13C-labeled glucose. In the postabsorptive state, MODY patients had
      normal glucose production (10.9 +/- 1.3 vs. 11.3 +/- 0.6 micromol x kg(-1) x min(
      1)) but decreased glucose cycling (0.6 +/- 0.3 vs. 1.5 +/- 0.3 micromol x kg(-1)
      x min(-1); P < 0.05) when compared with control subjects. However, at plasma
      glucose and insulin levels similar to those observed in MODY patients, control
      subjects' glucose production was markedly lower (3.2 +/- 1.5 micromol x kg(-1) x
      min(-1). After glucose ingestion, endogenous glucose production was reduced by
      only 29% in MODY patients compared with 80% in control subjects at a similar
      level of hyperglycemia (P < 0.05). This suggests that the V203A mutation of
      glucokinase results in decreased activity of glucokinase in liver cells. Thus
      endogenous glucose production is inadequately inhibited by hyperglycemia in MODY
      patients, possibly as a result of impaired hepatic glucokinase activity. These
      alterations contribute to the pathogenesis of hyperglycemia.

PMID- 9000696
TI  - Adrenalectomy prevents the obesity syndrome produced by chronic central
      neuropeptide Y infusion in normal rats.
AB  - Neuropeptide Y (NPY) in the hypothalamus plays an important role in the
      regulation of food intake and body weight and seems to be implicated in the
      etiology of obesity. When intracerebroventricularly (ICV) infused for 6 days in
      normal rats, NPY resulted in hyperphagia, increased body weight gain,
      hyperinsulinemia, hypercorticosteronemia, and hypertriglyceridemia compared with
      vehicle-infused control rats. NPY infusion also resulted in an insulin-resistant
      state in muscles and in a state of insulin hyperresponsiveness in white adipose
      tissue, as assessed by the measurement of the in vivo glucose utilization index
      of these tissues during euglycemic-hyperinsulinemic clamps. All of these hormono
      metabolic effects produced by chronic central NPY infusion were completely
      prevented when rats were adrenalectomized before NPY administration.
      Adrenalectomy per se had no effect on any of the parameters mentioned above. The
      levels of mRNA for the obese gene were increased in white adipose tissue after 6
      days of ICV NPY infusion in normal rats, and white adipose tissue weight was also
      increased. These effects of ICV NPY infusion were markedly decreased by prior
      adrenalectomy, although NPY infusion was able to somewhat enhance the low white
      adipose tissue obese mRNA levels and tissue weight of adrenalectomized rats. In
      conclusion, intact adrenal glands, and probably circulating corticosterone in
      particular, are necessary for the establishment of most of the hormonal and
      metabolic effects induced by chronic ICV infusion of NPY in normal rats.

PMID- 9000697
TI  - High-fat feeding impairs insulin-stimulated GLUT4 recruitment via an early
      insulin-signaling defect.
AB  - Glucose transport in skeletal muscle can be mediated by two separate pathways,
      one stimulated by insulin and the other by muscle contraction. High-fat feeding
      impairs glucose transport in muscle, but the mechanism remains unclear. FVB mice
      (3 weeks old) were fed a high-fat diet (55% fat, 24% carbohydrate, 21% protein)
      or standard chow for 3-4 weeks or 8 weeks. Insulin-stimulated glucose transport,
      assessed with either 2-deoxyglucose or 3-O-methylglucose was decreased 35-45% (P
      < 0.001) in isolated soleus muscle, regardless of diet duration. Similarly,
      glucose transport stimulated by okadaic acid, a serine/threonine phosphatase
      inhibitor, was also 45% lower with high-fat feeding, but the glucose transport
      response to hypoxia or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7)
      (which are stimulators of the "contraction pathway") was intact. Hexokinase I,
      II, and total activity were normal in soleus muscle from high-fat-fed mice. GLUT4
      expression in soleus muscle from the high-fat-fed mice was also normal, but the
      insulin-stimulated cell surface recruitment of GLUT4 assessed by exofacial
      photolabeling with [3H]-ATB bis-mannose was reduced by 50% (P < 0.001). Insulin
      receptor substrate 1 (IRS-1) associated phosphatidylinositol (PI) 3-kinase
      activity stimulated by insulin was also reduced by 36% (P < 0.001), and
      expression of p85 and p110b subunits of PI 3-kinase was normal. In conclusion,
      high-fat feeding selectively impairs insulin-stimulated, but not contraction
      pathway-mediated, glucose transport by reducing GLUT4 translocation to the plasma
      membrane. This appears to result from an acquired defect in insulin activation of
      PI 3-kinase. Since effects of okadaic acid on glucose transport are independent
      of PI 3-kinase, a second signaling defect may also be induced.

PMID- 9000698
TI  - The effect of pioglitazone on hepatic glucose uptake measured with indirect and
      direct methods in alloxan-induced diabetic dogs.
AB  - Pioglitazone, a thiazolidinedione derivative, ameliorates hyperglycemia by
      augmenting peripheral glucose disposal and suppressing hepatic glucose production
      in diabetic animals. However, the effect of this agent on hepatic glucose uptake
      has not been explored. To determine this, experiments were conducted in alloxan
      induced diabetic dogs with (pioglitazone group, n = 7) or without (control group,
      n = 5) a 10-day oral treatment with pioglitazone (1 mg x kg(-1) x day(-1)). A
      euglycemic-hyperinsulinemic (insulin infusion rate 25.2 pmol x kg(-1) x min(-1))
      clamp was maintained by adjusting the peripheral glucose infusion rate (GIR).
      After a 60-min basal period (period I), portal glucose infusion (Pinf, 33.3
      micromol x kg(-1) x min(-1)) was administered for 120 min (period II). This was
      followed by a 60-min recovery period (period III). Arterial insulin levels were
      kept stable in the supraphysiological range throughout the experiment (1,623 +/-
      52, pioglitazone group; 1,712 +/- 52 pmol/l, C group). There was no significant
      difference in whole-body glucose utilization determined by [3-3H]glucose between
      the pioglitazone and C groups in period I (68.4 +/- 2.8 vs. 70.1 +/- 2.8 micromol
      x kg(-1) x min(-1), respectively) and period III (81.2 +/- 5.0 vs. 74.5 +/- 3.3
      micromol x kg(-1) x min(-1), respectively). Net hepatic glucose uptake (NHGU)
      determined by arteriovenous difference method was approximately zero in the basal
      period (-0.7 +/- 1.1, pioglitazone group; 0.1 +/- 1.2 micromol x kg(-1) x min(
      1), C group). In period II, hepatic glucose uptake, determined by the changes in
      GIR, was significantly higher in the pioglitazone group (6.5 +/- 0.6 micromol x
      kg(-1) x min(-1)) than in the C group (-0.4 +/- 0.6 micromol x kg(-1) x min(-1),
      P < 0.001). This observation was also confirmed by NHGU during portal glucose
      infusion (6.9 +/- 1.4 vs. 2.1 +/- 1.8 micromol x kg(-1) x min(-1), pioglitazone
      vs. C, respectively; P < 0.025). We conclude that pioglitazone treatment enhances
      hepatic glucose uptake during portal glucose loading in alloxan-induced diabetic
      dogs. However, in hyperinsulinemic conditions, pioglitazone does not enhance the
      already high peripheral glucose uptake.

PMID- 9000699
TI  - Low stress response enhances vulnerability of islet cells in diabetes-prone BB
      rats.
AB  - In islet cells isolated from normal outbred Wistar rats, the known high
      vulnerability of islet cells toward oxygen radicals or nitric oxide can be
      abolished by inducing a stress response, such as by heat shock. We show here that
      islet cells from diabetes-prone BB rats are unable to mount such a protective
      response. Islet cells from diabetes-prone BB rats without recognizable insulitis
      were heat stressed. Subsequently, cells were exposed to nitric oxide, to oxygen
      radicals, or to the beta-cell toxin streptozotocin. While prior heat shock
      substantially increased the survival of toxin-treated Wistar rat islet cells, no
      protective stress response was noted for islet cells from diabetes-prone BB rats.
      Islet cells from diabetes-resistant BB rats were protected by heat stress to the
      same extent as Wistar rats. A survey of four additional major histocompatibility
      complex (MHC)-disparate rat strains confirmed the existence of a low and high
      responder type to stress. Parallel analysis of heat shock protein (hsp)70
      induction by Western blot showed a low and high hsp70 response phenotype. A high
      hsp70 response coincided with a protective stress response. The presence (or
      absence) of a protective stress response correlated with the preservation (or
      loss) of intracellular NAD+ in toxin-treated islet cells. The lack of a
      protective stress response in islet cells from diabetes-prone BB rats, but not in
      diabetes-resistant BB rats, may promote beta-cell lysis and autoantigen release,
      and hence could be important for initiation or propagation of the disease
      process.

PMID- 9000700
TI  - Systemic bias of cytokine production toward cell-mediated immune regulation in
      IDDM and toward humoral immunity in Graves' disease.
AB  - Disturbed immune regulation has been postulated to be crucial in the pathogenesis
      of IDDM and other autoimmune or allergic diseases. We therefore tested the
      hypothesis of a general bias in the peripheral immune system in patients with
      recent-onset IDDM or Graves' disease in comparison to healthy control subjects by
      studying whole blood cultures stimulated with phytohemagglutinin. Cells from IDDM
      patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma
      interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P
      = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels
      (interleukin [IL]-4, IL-10) were similar. Low levels of islet cell antibodies
      (ICAs) in IDDM patients were associated with high levels of Th1 and Th2
      cytokines. Antibodies to GAD, ICA512, or insulin did not correlate with
      individual cytokine profiles. Also, HLA-DQ types did not significantly correlate
      with either Th1 or Th2 cytokine production. Conversely, whole blood cultures from
      patients with Graves' disease (n = 18) produced significantly less TNF-alpha and
      IL-4 than normal subjects (P = 0.001-0.006). However, when the balance between
      Th1 and Th2 cytokine production was analyzed in individuals, the ratio between
      IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity
      in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production
      was seen in Graves' disease (P = 0.0001). The ratio of counterregulatory
      cytokines appeared to be the most reliable marker of the individual disease
      process. This study provides first evidence of a systemic bias in the immune
      regulation of humans, which might be either toward cell-mediated immunity (Th1)
      in IDDM or humoral immunity (Th2) in Graves' disease.

PMID- 9000701
TI  - Functional beta-cell mass after transplantation of human fetal pancreatic cells:
      differentiation or proliferation?
AB  - The scarcity of human adult islets available for transplantation in IDDM makes
      the use of human fetal pancreatic cells desirable. Human fetal pancreatic cells
      grow and differentiate after transplantation in nude mice. It is unclear whether
      proliferation of preexisting endocrine cells or differentiation of precursor
      cells is mainly responsible for the increased islet mass and if beta-cell
      enrichment before transplantation enhances the functional outcome of the graft.
      To answer these questions, we transplanted purified human fetal islets, islet
      like cell clusters (ICCs), and fresh tissue under the kidney capsule of nude
      mice. Insulin content was highest in the fresh tissue but fell rapidly during
      culture as either fetal islets or ICCs. Although fetal islets contained fourfold
      more insulin than ICCs before transplantation, the insulin content of the
      resulting grafts was the same after 3 months in vivo. The degree of stimulation
      after glucose challenge was comparable; however, more tissue was needed to
      generate the fetal islets. Grafts of fresh tissue also had similar total insulin
      contents, but when normalized to DNA, insulin concentration was significantly
      higher in the grafts from cultured tissue. Moreover, there were distinct
      morphological differences; the grafts from fresh tissue were more fibrous, with
      prominent ductal and cystic elements. Grafts from cultured tissue were two- to
      threefold enriched in endocrine tissue when compared with grafts originating from
      fresh tissue. These results suggest that islet cells identified in the grafted
      ICCs are mainly derived through differentiation of endocrine precursors and that
      cultured ICCs are more preferable than either fetal islets or uncultured tissue
      for transplantation.

PMID- 9000702
TI  - Pancreas transplantation restores epinephrine response and symptom recognition
      during hypoglycemia in patients with long-standing type I diabetes and autonomic
      neuropathy.
AB  - Impaired epinephrine secretion and symptom unawareness are characteristic of
      severe hypoglycemia in individuals with long-standing type I diabetes. Recently,
      the avoidance of clinical hypoglycemia has been reported to improve epinephrine
      and symptom responses to hypoglycemia in type I patients. However, the extent to
      which these defects can be restored in individuals with long-standing type I
      diabetes and autonomic neuropathy has not been assessed, nor has it been
      determined whether pancreas transplantation, which not only obviates hypoglycemia
      but also prevents hyperglycemia, results in the complete recovery of either
      epinephrine response or symptom awareness during insulin-induced hypoglycemia. We
      performed stepped hypoglycemic clamp studies in successful pancreas
      transplantation recipients to assess epinephrine and other counterregulatory
      hormone responses during hypoglycemia and to determine the degree to which
      hypoglycemic symptom recognition could be restored. Thirteen pancreas transplant
      recipients and matched control subjects were studied utilizing stepped
      hypoglycemic clamp protocol to achieve target glucose levels of 3.9, 3.3, 2.8,
      and 2.2 mmol/l (70, 60, 50, and 40 mg/dl, respectively). Plasma epinephrine
      response was significantly greater in healthy control subjects and pancreas
      transplant patients compared with type I subjects at the glucose plateaus of 3.9,
      3.3, and 2.8 mmol/l. However, epinephrine response in pancreas transplant
      recipients was significantly less than that seen in either healthy control
      subjects or nondiabetic kidney transplant recipients at each of these glucose
      plateaus. The magnitude of the epinephrine response in pancreas transplant type I
      patients did not correlate with either the duration of diabetes, the duration of
      transplantation, or the measures of autonomic nerve function. Hypoglycemic
      symptom recognition was significantly greater in pancreas transplant subjects
      than type I patients and did not differ between pancreas transplant and control
      groups. No improvement in norepinephrine response was observed after pancreas
      transplantation, while glucagon responses to hypoglycemia were normalized in
      pancreas transplant patients. In conclusion, these studies uniquely demonstrate
      that successful pancreas transplantation improves epinephrine response and
      normalizes hypoglycemia symptom recognition in patients with long-standing
      diabetes and established autonomic neuropathy. No correlation was observed
      between the severity of autonomic neuropathy or the duration of diabetes and the
      recovery of either the epinephrine or symptom responses to hypoglycemia.

PMID- 9000703
TI  - Reduced insulin, GLUT2, and IDX-1 in beta-cells after partial pancreatectomy.
AB  - Reduction of GLUT2 is associated with loss of glucose-induced insulin secretion
      in genetic and chemical diabetes and in transplanted islets exposed to chronic
      hyperglycemia. To examine the mechanisms for this loss of GLUT2 in normal islets
      exposed to hyperglycemia, we performed studies on Sprague Dawley rats 4 weeks
      after a 90% partial pancreatectomy (Px), a well-characterized model of
      hyperglycemia. GLUT2 immunofluorescence in the beta-cell of Px rats was greatly
      reduced. Western blot analysis of homogenates of isolated Px islets also showed a
      reduction in GLUT2 protein; densitometry measurements were 36 +/- 3% of values
      from islets of sham-operated controls. Insulin protein levels were decreased to a
      similar extent. Islet GLUT2 and insulin mRNA were measured with quantitative
      reverse transcriptase-polymerase chain reaction. The level of GLUT2 mRNA from Px
      islets was 24 +/- 4% of that of islets from sham-operated controls; similar
      results were obtained for insulin. Because both these beta-cell-specific messages
      were reduced, we analyzed the Px islets for the pancreas-duodenum-specific
      transcription factor IDX-1(IPF-1, STF-1, PDX-1) protein. It was markedly reduced
      (approximately 80%) in islets from the Px rats. These data suggest that 1) the
      loss of GLUT2 protein associated with hyperglycemia is at least partially
      explained by reduced levels of the GLUT2 gene transcripts; 2) the reduction of
      beta-cell insulin content during chronic hyperglycemia may not be completely due
      to degranulation (reduced levels of gene transcripts may play a role); and 3) the
      reduction in the transcription factor IDX-1 raises the possibility that
      dysregulation of transcription factors may contribute to the abnormal beta-cell
      function found in states of chronic hyperglycemia.

PMID- 9000704
TI  - Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM
      patients on insulin-analog treatment. Multicenter Insulin Lispro Study Group.
AB  - Insulin lispro, an insulin analog recently developed particularly for mealtime
      therapy, has a fast absorption rate and a short duration of action. We compared
      insulin lispro and regular human insulin in the mealtime treatment of 1,008
      patients with IDDM. The study was a 6-month randomized multinational (17
      countries) and multicenter (102 investigators) clinical trial performed with an
      open-label crossover design. Insulin lispro was injected immediately before the
      meal, and regular human insulin was injected 30-45 min before the meal.
      Throughout the study, the postprandial rise in serum glucose was significantly
      lower during insulin lispro therapy. At the endpoint, the postprandial rise in
      serum glucose was reduced at 1 h by 1.3 mmol/l and at 2 h by 2.0 mmol/l in
      patients treated with insulin lispro (P < 0.001). The rate of hypoglycemia was
      12% less with insulin lispro (6.4 +/- 0.2 vs. 7.2 +/- 0.3 episodes/30 days, P <
      0.001), independent of basal insulin regimen or HbA1c level. The reduction was
      observed equally in episodes with and without symptoms. When the total number of
      episodes for each patient was analyzed according to the time of occurrence, the
      number of hypoglycemic episodes was less with insulin lispro than with regular
      human insulin therapy during three of four quarters of the day (P < 0.001). The
      largest relative improvement was observed at night. In conclusion, insulin lispro
      improves postprandial control, reduces hypoglycemic episodes, and improves
      patient convenience, compared with regular human insulin, in IDDM patients.

PMID- 9000705
TI  - Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes
      Control and Complications Trial Research Group.
AB  - A total of 1,441 patients with IDDM were randomly assigned to receive either
      intensive (n = 711) or conventional (n = 730) diabetes therapy in the Diabetes
      Control and Complications Trial (DCCT). The patients were followed for an average
      of 6.5 years. Subjects were instructed to report all episodes of suspected severe
      hypoglycemia to their health care team. In addition, at quarterly follow-up
      visits, each subject was asked about the occurrence of severe hypoglycemia. There
      were 3,788 episodes of severe hypoglycemia (requiring assistance); 1,027 of these
      episodes were associated with coma and/or seizure. A total of 65% percent of
      patients in the intensive group vs. 35% of patients in the conventional group had
      at least one episode of severe hypoglycemia by the study end; the overall rates
      of severe hypoglycemia were 61.2 per 100 patient-years vs. 18.7 per 100 patient
      years in the intensive and conventional treatment groups, respectively, with a
      relative risk (RR) of 3.28. The relative risk for coma and/or seizure was 3.02
      for intensive therapy. The increased risk with intensive treatment persisted over
      each of the 9 years of follow-up in the DCCT and over the calendar years 1984
      1993 during which the study was conducted. When baseline patient characteristics
      were examined for effects on the risk of severe hypoglycemia, the relative risk
      of hypoglycemia for intensive versus conventional treatment was > or = 2 for all
      subgroups. Several subgroups defined by baseline characteristics, including
      males, adolescents, and subjects with no residual C-peptide or with a prior
      history of hypoglycemia, had a particularly high risk of severe hypoglycemia in
      both treatment groups. Analyses of the cumulative incidence of successive
      episodes indicated that intensive treatment was also associated with an increased
      risk of multiple episodes within the same patient (e.g., 22% experienced five or
      more episodes of severe hypoglycemia within the first 5 years of follow-up vs. 4%
      in the conventional group). Within both treatment groups, patients who
      experienced severe hypoglycemia were at increased risk of subsequent episodes.
      Approximately 30% of patients in each group experienced a second episode within
      the 4 months following the first episode of severe hypoglycemia. Within each
      treatment group, the number of prior episodes of hypoglycemia was the strongest
      predictor of the risk of future episodes, followed closely by the current HbA1c
      value. After adjustment for the current quarterly HbA1c level, intensive
      treatment was still associated with a significantly increased risk of
      hypoglycemia, indicating that the increased risk with intensive treatment is not
      completely explained by differences in HbA1c values.

PMID- 9000706
TI  - Polymorphism in the 5'-end of the aldose reductase gene is strongly associated
      with the development of diabetic nephropathy in type I diabetes.
AB  - Recent studies suggest that the gene encoding aldose reductase (ALR2), the enzyme
      that converts glucose to sorbitol, may confer susceptibility to microvascular
      disease. DNA from 275 British Caucasian patients with type I diabetes and 102
      normal healthy control patients were typed for a (CA)n dinucleotide repeat
      polymorphic marker in the 5'-region of the ALR2 gene using polymorase chain
      reaction (PCR). A highly significant decrease in the frequency of the Z+2 allele
      was found in patients with nephropathy (nephropathy group) compared with those
      with no complications after a 20-year duration of diabetes (uncomplicated group)
      (12.7 vs. 38.2%, respectively, chi2 = 18.6, P < 0.00001); this was accompanied by
      an increase in the Z-2 allele in the nephropathy group (32.0 vs. 12.7% in the
      uncomplicated group). The nephropathy group also had a significant decrease in
      the Z/Z+2 genotype compared with the uncomplicated patients (10.7 vs. 44.7%, chi2
      = 16.0, P < 0.0001) and an increased frequency of the Z/Z-2 genotype. There was
      no significant association with diabetic retinopathy. These results demonstrate
      that the ALR2 gene may play a role in susceptibility to diabetic nephropathy;
      individuals with the Z+2 allele are more than seven times less likely to develop
      diabetic renal disease than those without this marker. This marker may prove
      valuable in screening for patients with diabetic nephropathy at diagnosis of
      diabetes.

PMID- 9000707
TI  - Aldose reductase inhibition protects diabetic and nondiabetic rat hearts from
      ischemic injury.
AB  - Diabetes increases the incidence of cardiovascular disease as well as the
      complications of myocardial infarction. Studies using animal models of diabetes
      have demonstrated that the metabolic alterations occurring at the myocyte level
      may contribute to the severity of ischemic injury in diabetic hearts. Of the
      several mechanisms being investigated to understand the pathogenesis of diabetic
      complications, the increased metabolism of glucose via the polyol pathway has
      received considerable attention. Deviant metabolic regulation due to increased
      flux through aldose reductase in diabetic hearts may influence the ability of the
      myocardium to withstand ischemia insult. To determine if aldose reductase
      inhibition improves tolerance to ischemia, hearts from acute type I diabetic and
      nondiabetic control rats were isolated and retrograde perfused. Each group was
      exposed to 1 micromol/l zopolrestat, a specific inhibitor of aldose reductase,
      for 10 min, followed by 20 min of global ischemia and 60 min of reperfusion in
      the absence of zopolrestat. Zopolrestat reduced sorbitol levels before ischemia
      in diabetic hearts. The cytosolic redox state (NADH/NAD+), as measured by lactate
      to-pyruvate ratios, was significantly lowered under baseline, ischemic, and
      reperfusion conditions in diabetic hearts perfused with zopolrestat. In these
      diabetic hearts, ATP was significantly higher in zopolrestat hearts during
      ischemia, as were phosphocreatine and left ventricular-developed pressure on
      reperfusion. Zopolrestat provided similar metabolic and functional benefits in
      nondiabetic hearts. Creatine kinase release was reduced by approximately 50% in
      both nondiabetic and diabetic hearts treated with zopolrestat. These data
      indicate that inhibition of aldose reductase activity preserves high-energy
      phosphates, maintains a lower cytosolic NADH/NAD+ ratio, and markedly protects
      both diabetic and nondiabetic hearts during ischemia and reperfusion.

PMID- 9000708
TI  - Supplemental myo-inositol prevents L-fucose-induced diabetic neuropathy.
AB  - Nerve myo-inositol depletion, which has been implicated in the pathogenesis of
      acute experimental diabetic neuropathy, can be reproduced in normal rats by
      feeding diets enriched in L-fucose, a competitive inhibitor of sodium-dependent
      myo-inositol transport. Previously, we reported that L-fucose feeding for 6 weeks
      reproduces the effect of experimental diabetes on nerve Na+-K+-ATPase activity
      and conduction velocity, which can be prevented by simultaneous dietary myo
      inositol supplementation. To further validate this model of myo-inositol
      depletion, we examined the effects of long-term (24-week) L-fucose feeding and
      dietary myo-inositol supplementation on nerve Na+-K+-ATPase, nerve conduction
      velocity, and myelinated nerve fiber pathology. After 24 weeks of L-fucose
      enriched (10 or 20%) diets, nerve myo-inositol levels and Na+-K+-ATPase activity
      decreased significantly (P < 0.05) and were associated with a 25-30% reduction in
      nerve conduction velocity, all of which were completely prevented by 1% dietary
      myo-inositol. Twenty percent L-fucose diet resulted in significant axonal
      atrophy, paranodal swelling (P < 0.001), and paranodal demyelination (P < 0.005),
      without increasing Wallerian degeneration or nerve fiber loss, a pattern
      qualitatively similar to that seen in early murine diabetic neuropathy. Dietary
      myo-inositol supplementation prevented these structural changes and increased
      nodal remyelination, supporting a role of myo-inositol depletion in the genesis
      of early diabetic neuropathy. The L-fucose model system may therefore serve as an
      experimental tool to elucidate the pathophysiological role of isolated myo
      inositol depletion and its consequences in the multifactorial pathogenesis of
      diabetic neuropathy.

PMID- 9000709
TI  - No independent associations of LMP2 and LMP7 polymorphisms with susceptibility to
      develop IDDM.
AB  - Results from a recent study suggested that polymorphisms within the HLA class II
      genes LMP2 and LMP7 were associated with the susceptibility for developing IDDM,
      and that this association could not be explained by linkage disequilibrium to HLA
      DR or -DQ genes. We typed 285 IDDM patients and 337 HLA-DRB1-DQA1-DQB1
      genotypically matched control subjects from an ethnically homogeneous population
      for both the G/T polymorphism in intron 6 of the LMP7 gene and the Arg-His
      polymorphism in the LMP2 gene. In addition, we typed IDDM families in which at
      least one parent was homozygous for a DRB1-DQA1-DQB1 haplotype and performed a
      transmission/disequilibrium test of these LMP polymorphisms. Our data suggest
      that none of these LMP2 or LMP7 polymorphisms are independently associated with
      IDDM susceptibility, in contrast to what has been previously reported by others.
      Further, our results suggest that one partial explanation for the previously
      reported independent association between IDDM and these LMP polymorphisms may
      have been that patients and control subjects were not matched for DRB1*04
      subtypes. Our results emphasize the need for a complete matching for DRB1, DQA1,
      and DQB1 alleles between patients and control subjects when attempting to detect
      independent effects of other polymorphisms in the HLA complex on IDDM
      susceptibility or protection.

PMID- 9000710
TI  - Expression of the functional leptin receptor mRNA in pancreatic islets and direct
      inhibitory action of leptin on insulin secretion.
AB  - Leptin, encoded for by the mouse ob gene, regulates feeding behavior and energy
      metabolism. Its receptor (Ob-R) is encoded by the mouse diabetic (db) gene and is
      mutated in the db/db mouse so that it lacks the cytoplasmic domain. We show that
      the full-length leptin receptor (Ob-Rb), which is believed to transmit the leptin
      signal, is expressed in pancreatic islets of ob/ob and wild-type mice, as well as
      in hypothalamus, liver, kidney, spleen, and heart. Recombinant leptin inhibited
      basal insulin release in the perfused pancreas preparation from ob/ob mice but
      not in that from Zucker fa/fa rats. Leptin (1-100 nmol/l) also produced a dose
      dependent inhibition of glucose-stimulated insulin secretion by isolated islets
      from ob/ob mice. In contrast, leptin at maximum effective concentration (100
      nmol/l) did not inhibit glucose-stimulated insulin secretion by islets from db/db
      mice. These results provide evidence that a functional leptin receptor is present
      in pancreatic islets and suggest that leptin overproduction, particularly from
      abdominal adipose tissue, may modify directly both basal and glucose-stimulated
      insulin secretion.

PMID- 9000711
TI  - Cotransplantation of allogeneic islets with allogeneic testicular cell aggregates
      allows long-term graft survival without systemic immunosuppression.
AB  - We prepared single-cell suspensions of Lewis rat ?RT1(1/l)? testicular cells and
      cultured these in vitro for 48 h under conditions that promoted the formation of
      cellular aggregates. In the absence of systemic immunosuppression, the
      transplantation of a sufficient quantity of these aggregates (containing 11 x
      10(6) cells, (75% Sertoli cells), together with 2,000 purified Lewis rat islets,
      reversed the diabetic state for >95 days in 100% (5/5) of the chemically diabetic
      Wistar-Furth ?RT1(u/u)? recipients. Similar grafts consisting of islets alone or
      islets plus 50% fewer testicular cell aggregates survived for only 10 days.
      Functioning composite allografts harvested from normoglycemic animals at
      approximately 100 days showed healthy beta-cells in close association with Fas
      ligand-expressing Sertoli cells. Because no gene therapy protocol is required,
      the transplantation of composite grafts consisting of purified human allogeneic
      islets plus human allogeneic testicular cell aggregates can be applied in
      clinical islet transplantation as soon as it has been proven in a large animal
      model.

PMID- 9000712
TI  - From acute to chronic pain: mechanisms and hypotheses.

PMID- 9000713
TI  - Quantitative experimental assessment of pain and hyperalgesia in animals and
      underlying neural mechanisms.

PMID- 9000714
TI  - Nociceptive, environmental and neuroendocrine factors determining pain behaviour
      in animals.

PMID- 9000715
TI  - Functional imaging studies of the pain system in man and animals.

PMID- 9000716
TI  - Limbic processes and the affective dimension of pain.

PMID- 9000717
TI  - Neurogenic mechanisms and neuropeptides in chronic pain.

PMID- 9000718
TI  - Peripheral opioid analgesia--facts and mechanisms.

PMID- 9000719
TI  - Alterations in the functional properties of dorsal root ganglion cells with
      unmyelinated axons after a chronic nerve constriction in the rat.

PMID- 9000720
TI  - Plasticity of messenger function in primary afferents following nerve injury-
      implications for neuropathic pain.

PMID- 9000721
TI  - The possible role of substance P in eliciting and modulating deep somatic pain.

PMID- 9000722
TI  - Studies of the release of immunoreactive galanin and dynorphin A(1-8) in the
      spinal cord of the rat.

PMID- 9000724
TI  - Neurophysiology of chronic inflammatory pain: electrophysiological recordings
      from spinal cord neurons in rats with prolonged acute and chronic unilateral
      inflammation at the ankle.

PMID- 9000723
TI  - Cooperative mechanisms of neurotransmitter action in central nervous
      sensitization.

PMID- 9000725
TI  - Acute mechanical hyperalgesia in the rat can be produced by coactivation of
      spinal ionotropic AMPA and metabotropic glutamate receptors, activation of
      phospholipase A2 and generation of cyclooxygenase products.

PMID- 9000726
TI  - Involvement of glutamatergic neurotransmission and protein kinase C in spinal
      plasticity and the development of chronic pain.

PMID- 9000727
TI  - Neurobiology of spinal nociception: new concepts.

PMID- 9000728
TI  - Balances between excitatory and inhibitory events in the spinal cord and chronic
      pain.

PMID- 9000729
TI  - Plasticity of the nervous system at the systematic, cellular and molecular
      levels: a mechanism of chronic pain and hyperalgesia.

PMID- 9000730
TI  - The detection of breast microcalcifications with medical ultrasound.
AB  - Microcalcifications are small crystals of calcium apatites which form in human
      tissue through a number of mechanisms. The size, morphology, and distribution of
      microcalcifications are important indicators in the mammographic screening for
      and diagnosis of various carcinomas in the breast. Although x-ray mammography is
      currently the only accepted method for detecting microcalcifications, its
      efficacy in this regard can be reduced in the presence of dense parenchyma.
      Current ultrasound scanners do not reliably detect microcalcifications in the
      size range of clinical interest. The results of theoretical, simulation, and
      experimental studies focused on the improvement of the ultrasonic visualization
      of microcalcifications are presented. Methods for estimating the changes in
      microcalcification detection performance which result from changes in aperture
      geometry or the presence of an aberrator are presented. An analysis of the
      relative efficacy of spatial compounding and synthetic receive aperture
      geometries in the detection of microcalcifications is described. The impact of
      log compression of the detected image on visualization is discussed. Registered
      high resolution ultrasound and digital spot mammography images of
      microcalcifications in excised breast carcinoma tissue and results from the
      imaging of suspected microcalcifications in vivo are presented.

PMID- 9000731
TI  - Nonlinear propagation applied to the improvement of resolution in diagnostic
      medical ultrasound.
AB  - Medical B-mode scanners operating under conditions typically encountered during
      clinical work produce ultrasonic wave fields that undergo nonlinear distortion.
      In general, the resulting harmonic beams are narrower and have lower sidelobe
      levels than the fundamental beam, making them ideal for imaging purposes. This
      work demonstrates the feasibility of nonlinear harmonic imaging in medical
      scanners using a simple broadband imaging arrangement in water. The ultrasonic
      system comprises a 2.25-MHz circular transducer with a diameter of 38 mm, a
      membrane hydrophone, also with a diameter of 38 mm, and a polymer lens with a
      focal length of 262 mm. These components are arranged coaxially giving an imaging
      geometry similar to that used in many commercial B-scanners, but with a receiver
      bandwidth sufficient to record the first four harmonics. A series of continuous
      wave and pulse-echo measurements are performed on a wire phantom to give 1-D
      transverse pressure profiles and 2-D B-mode images, respectively. The reflected
      beamwidths wn decrease as wn/W1 = 1/n0.78, where n is the harmonic number, and
      the reflected sidelobe levels fall off quickly with increasing n. In imaging
      terms, these effects correspond to a large improvement in lateral resolution and
      signal-to-clutter ratio for the higher harmonics.

PMID- 9000732
TI  - Development of distortion product emissions in the gerbil: "filter" response and
      signal delay.
AB  - Amplitude and phase responses of distortion product otoacoustic emissions as a
      function of stimulus frequency ratio were measured for frequencies between 2 and
      48 kHz, in Mongolian gerbils (Meriones unguiculates) aged 15 to 30 days after
      birth. After baseline measurements, furosemide was administered to distinguish
      active from passive emissions. At all ages, structure in the form of multiple
      peaks was observed in the amplitude responses of specific odd-order emissions.
      This structure depended on the emission frequency, not the stimulus frequency
      ratio, and did not generally depend on the stimulus amplitude. Nor was it
      dependent on the functioning of the cochlear amplifier: At moderate stimulus
      levels, the observed emission distribution simply shifted to lower amplitudes
      when the cochlear amplifier was made temporarily dysfunctional by furosemide
      injection. The center frequencies and widths of the peaks in the amplitude
      response did not generally change with age, except that the relative amplitudes
      of the higher-frequency peaks were increased in younger animals. At 2 kHz,
      however, the distribution showed other evidence of maturation, with the frequency
      of maximum emission moving downward with age. The phase responses yielded
      estimates of the round trip signal (group or traveling wave) delay. At a given
      frequency, the active signal delay typically decreased substantially with
      increasing stimulus level. However, there was a rapid variation in delay as the
      stimulus level passed the normal active-passive crossover level. At stimulus
      levels measured relative to the active-passive crossover level, i.e., either 20
      or 30 dB lower, the active signal delay decreased only slightly with age.
      Overall, both filter response and signal delay characteristics were found to be
      essentially mature near the onset of hearing.

PMID- 9000733
TI  - Detectability of simultaneously masked signals as a function of masker bandwidth
      and configuration for different signal delays.
AB  - Signal detectability was measured in three temporal conditions as a function of
      the bandwidth and configuration of simultaneous maskers that either did or did
      not spectrally overlap the signal. The 20-ms signal was 250 Hz wide and was
      centered at 2500 Hz (fs). Although there were marked individual differences,
      performance was typically poorer when signal onset came 1 ms rather than 250 ms
      after the onset of a 420-ms masker, and poorest when signal onset came 1 ms after
      the onset of a 23-ms masker. The results support the idea that two separate
      across-channel processes contribute to temporal changes in signal detectability.
      One process contributes to the improvement observed as signal onset is delayed
      from masker onset, and its influence is reduced by the presence of masking
      components at fs only when the masker extends exclusively below fs. The other
      process is associated with the improvement observed as masker offset is delayed
      from signal offset, and its influence is reduced by the presence of masking
      components at fs when the masker extends exclusively above, or both below and
      above fs. Both of these processes are primarily activated by frequencies ranging
      from 0.6 to 0.8fs and 1.2 to 1.4fs. The data also demonstrate that the measured
      critical bandwidth narrows as signal onset is delayed from masker onset.

PMID- 9000734
TI  - A comparison of detection and discrimination of temporal asymmetry in amplitude
      modulation.
AB  - Two compound experiments were performed to compare the detection of amplitude
      modulation with the discrimination of modulator shape when the modulators have
      strong temporal asymmetry. In experiment 1, an adaptive procedure was used to
      measure detection and discrimination as a function of modulation frequency from 4
      to 400 Hz. In experiment 2, the method of constant stimuli was used to measure
      psychometric functions for detection and discrimination at one modulation
      frequency, 8 Hz. The asymmetric modulators were time-reversed pairs. Thus their
      envelope spectra are identical and models based on the envelope spectrum would
      predict no effect of asymmetry on detection or discrimination at any modulation
      depth. The detection results show, as predicted, that the direction of asymmetry
      does not affect the detectability of modulation in either experiment. In
      contrast, the discrimination results show that direction of asymmetry is readily
      discriminable for modulation frequencies less than about 50 Hz, indicating that
      envelope-spectrum models will require modification if they are to be extended to
      include discrimination of temporal asymmetry.

PMID- 9000735
TI  - Comparison of electrode discrimination, pitch ranking, and pitch scaling data in
      postlingually deafened adult cochlear implant subjects.
AB  - The goal of this study was to investigate the relationship between variation in
      electrode site of stimulation and the perceptual dimensions along which such
      stimuli vary. This information may allow more effective use of electrode place
      when encoding speech information. To achieve this goal, two procedures which
      measure pitch in subjects implanted with the Nucleus/Cochlear Corporation
      multichannel device were performed. Estimates of electrode discriminability that
      can be obtained from these procedures were compared to a more direct measure of
      electrode discriminability that was obtained in a previous study [Collins et al.,
      Assoc. Res. Otolaryng. Abstracts, No. 642 (1994)]. In the first task, subjects
      performed a pitch ranking procedure similar to that used in previous studies
      [Townshend et al., J. Acoust. Soc. Am. 82, 106-115 (1987); Nelson et al., J.
      Acoust. Soc. Am. 98, 1987-1999 (1995)]. Estimates of the pitch percept elicited
      by stimulation of each electrode as well as the discriminability of the
      electrodes were generated from the data using two different statistical analyses.
      In the second task, subjects performed a pitch scaling procedure similar to one
      used in a previous study [Busby et al., J. Acoust. Soc. Am. 95, 2658-2669
      (1994)]. Again, two different statistical analyses were performed to generate
      estimates of the pitch percept corresponding to stimulation of each electrode and
      to generate estimates of electrode discriminability. In general, the estimates of
      the relationships between the pitch percepts obtained from the two procedures
      were not identical. In addition, the estimates of electrode discriminability were
      not equivalent to the electrode discrimination measures obtained from the same
      subjects during the previous study. Signal detection theory has been used to
      model the decision processes required by each of the procedures described above
      [e.g., Jesteadt and Bilger, J. Acoust. Soc. Am. 55, 1266-1276 (1974)]. However,
      these models do not predict the differences that were observed between the data
      sets obtained during this study. An alternate model is proposed which may explain
      the data obtained from these subjects. This model is based on the assumption that
      the percept that is elicited by electrical stimulation of an electrode is
      multidimensional, as opposed to unidimensional in nature. Therefore, the
      perceived signal is more appropriately modeled using a multidimensional random
      vector, where each element of the vector represents the perceived value of one of
      the dimensions of the signal.

PMID- 9000736
TI  - Acoustic characteristics of the piriform fossa in models and humans.
AB  - The piriform fossa forms the bottom part of the pharynx and acts as a pair of
      side branches of the vocal tract. Because of its obscure form and function, the
      piriform fossa has usually been neglected in the current speech production
      models. This study examines the geometric and acoustic characteristics of the
      piriform fossa by means of MRI-based mechanical modeling, in-vivo experiments and
      numerical computations. Volumetric MRI data showed that the piriform fossa is 2.1
      to 2.9 cm3 in volume and 1.6 to 2.0 cm in depth for four Japanese subjects (three
      males and one female). The results obtained from mechanical models showed that
      the piriform fossa contributes strong troughs, i.e., spectral minima, to speech
      spectra in a region of 4 to 5 kHz. The antiresonances were identified with
      increasing frequency when water was injected into the piriform fossa of human
      subjects in in-vivo experiments. Antiresonances obtained from the experiments and
      simulations were confirmed to be consistent with those in natural speech within
      5%. Acoustic measurements and simulations showed that the influence of the
      piriform fossa extends to the lower vowel formants in addition to the local
      troughs. This global effect can be explained by the location of the fossa near
      the glottal end of the vocal tract.

PMID- 9000737
TI  - Glottal characteristics of female speakers: acoustic correlates.
AB  - The aim of the research reported in this paper is to formulate a set of acoustic
      parameters of the voicing source that reflect individual differences in the voice
      qualities of female speakers. Theoretical analysis and observations of
      experimental data suggest that a more open glottal configuration results in a
      glottal volume-velocity waveform with relatively greater low-frequency and weaker
      high-frequency components, compared to a waveform produced with a more adducted
      glottal configuration. The more open glottal configuration also leads to a
      greater source of aspiration noise and larger bandwidths of the natural
      frequencies of the vocal tract, particularly the first formant. These different
      attributes of the glottal waveform can be measured directly from the speech
      spectrum or waveform. A set of acoustic parameters that are likely to indicate
      glottal characteristics is described. These parameters are measured in the speech
      of a group of female speakers, and the glottal configurations of the speakers are
      hypothesized. This research contributes to the description of normal variations
      of voicing characteristics across speakers and to a continuing effort to improve
      the analysis and synthesis of female speech. It may also have applications in
      clinical settings.

PMID- 9000738
TI  - Automatic integrated analysis of jaw and lip movement in speech production.
AB  - A noninvasive methodology for studying the kinematics of speech production is
      presented. It is based on the tracking of very small and light passive markers
      attached to the subjects' face. Using a pair of TV cameras, the 3-D markers'
      positions are computed in real time, at a subpixel accuracy, by a dedicated
      hardware. From these data, the time course of a set of parameters which describe
      lip and jaw movement is computed; in addition, a semiautomatic procedure that
      identifies the exact onset and offset of the investigated sequences has been
      developed. To compare the results over different productions, a time
      normalization procedure based on a continuous inverse Fourier transform has been
      implemented.

PMID- 9000739
TI  - Perception of nonlinear and linear formant trajectories.
AB  - Perception of F2 trajectories in synthetic vowels was investigated. Perceptual
      boundaries (50% response points of identification functions) of 20-step/U
      I/continua with various shapes of F2 trajectories were determined and compared
      with the boundary for vowels with steady-state F2. In experiment 1, the vowels
      were synthesized in either/j-j/or/w-w/context resulting in parabolic
      trajectories, then the stimuli were split into halves resulting in quadratic F2
      trajectories. All stimuli were 200 ms long. For the/wVw/, and/wV/stimuli, the
      boundaries were at lower stimulus numbers than for the stimuli with steady-state
      F2, indicating that the nonlinear F2 trajectories were perceived as having
      frequencies beyond the extreme values actually synthesized in the stimuli. This
      type of signal processing has been termed "perceptual compensation." For the
      /jVj/ stimuli, there was only a trend for perceptual compensation of F2
      trajectories. For the/Vw/,/Vj/, and/jV/stimuli, the boundaries were at stimulus
      numbers corresponding to frequencies of the relatively steady-state vowel-like
      segments. In experiment 2, the quadratic F2 trajectories of the/wV/stimuli were
      changed to linear trajectories and F1 and F3 trajectories were either quadratic,
      linear, or steady state. The results indicated that the shape of F1 and F3
      trajectories had no effect on the boundaries. For the linear F2 trajectories, as
      for the quadratic F2 trajectories in the/wV/ stimuli, the boundaries were at
      lower stimulus numbers than for the stimulus with steady-state F2, indicating
      presence of perceptual compensation. In the experiment 3, the F1 and F3 were
      steady state and the linear F2 trajectories had three different values of
      frequency difference, delta F, between the initial and final frequencies. The
      perceptual compensation was found for the 200-ms stimuli with large delta F up to
      500 Hz over 200-ms stimulus duration, and perceptual enhancement of final
      frequencies was found for the stimuli with delta F = 280 Hz.

PMID- 9000740
TI  - Effect of reducing temporal intensity modulations on sentence intelligibility.
AB  - Modulations in the temporal intensity envelope of 24 1/4-octave bands were
      reduced by proportionally raising the troughs and lowering the peaks relative to
      the mean intensity in each band. The effect on intelligibility of various degrees
      of modulation reduction was investigated by measuring the speech-reception
      threshold (SRT) in noise. For conditions of severe modulation reduction, the
      number of correctly received sentences in quiet was scored. The effect of this
      deterministic modulation reduction was compared to the effect of stochastic
      modulation reduction obtained with addition of noise. Results for 12 normal
      hearing subjects show that in the case of deterministic modulation reduction,
      intelligibility is reduced to 50% when the modulation-transfer factor equals
      0.10, whereas in the case of modulation reduction by addition of noise, this
      intelligibility is reached already at a modulation-transfer factor of 0.27. This
      confirms that the effect of additive noise on intelligibility cannot be
      understood completely as a result of only modulation reduction. As suggested by
      Drullman [J. Acoust. Soc. Am. 97, 585-592 (1995)] two other factors associated
      with the addition of noise have to be taken into account: (1) the introduction of
      nonrelevant modulations, and (2) the corruption of the fine structure.

PMID- 9000741
TI  - Spectral balance as a cue in the perception of linguistic stress.
AB  - In this study, the claim that intensity, as an acoustic operationalization of
      loudness, is a weak cue in the perception of linguistic stress is reconsidered.
      This claim is based on perception experiments in which loudness was varied in a
      naive way: All parts of the spectrum were amplified uniformly, i.e., loudness was
      implemented as intensity or gain. In an earlier study it was found that if a
      speaker produces stressed syllables in natural speech, higher frequencies
      increase more than lower frequencies. Varying loudness in this way would
      therefore be more realistic, and should bring its true cue value to the surface.
      Results of a perception experiment bear out that realistic intensity level
      manipulations (i.e., concentrated in the higher frequency bands) provide stronger
      stress cues than uniformly distributed intensity differences, and are close in
      strength to duration differences.

PMID- 9000742
TI  - Prosodic features at discourse boundaries of different strength.
AB  - This paper presents the design and the evaluation of a method to study prosodic
      features of discourse structure in unrestricted spontaneous speech. Past work has
      indicated that one of the major difficulties that discourse prosody analysts have
      to overcome is finding an independent specification of hierarchical discourse
      structure as to avoid circularity. Previous studies have tried to solve this
      problem by constraining the discourse or by basing segmentations on a specific
      discourse theory. The current investigation first explores the possibility of
      experimentally determining discourse boundaries in unrestricted speech. In a next
      stage, it is investigated to what extent boundaries obtained in this way
      correlate with specific prosodic variables: the features pause, pitch range, and
      type of boundary tone are studied as a function of discourse structure.

PMID- 9000743
TI  - Ultrasonic wave propagation in bovine cancellous bone.
AB  - The acoustic properties of bovine cancellous (spongy) bone have been
      experimentally studied in vitro by the pulse transmission technique. Fast and
      slow longitudinal waves have been clearly identified when the acoustic wave
      propagates parallel to the direction of the trabeculae. Propagation speeds and
      attenuation of the fast and slow waves were observed in the frequency range of
      0.5-5 MHz. Theoretical discussion is given to Biot's theory and the propagation
      of sound waves in fluid-saturated porous media.

PMID- 9000745
TI  - In vitro and in vivo enhancement of sonodynamically active cavitation by second
      harmonic superimposition.
AB  - Acoustic cavitation, the primary mechanism of sonochemical effects, is known to
      be induced more easily by standing waves than by progressive waves. It has been
      found that acoustic cavitation can be an order of magnitude enhanced by
      superimposing the second harmonic on the fundamental. Significant synergistic
      effects between the fundamental and the second harmonic were observed in both in
      vitro and in vivo experiments employing a progressive wave field. Second-harmonic
      superimposition induces in vitro sonochemical reaction as well as fractional
      harmonic emission at a relatively low ultrasonic intensity even in a progressive
      wave field. The effect of second-harmonic superimposition was also investigated
      using exteriorized mouse livers suspended in degassed saline. The intensity
      threshold for the production of focal tissue damage, paired with fractional
      harmonic emission was significantly lowered by second-harmonic superimposition
      especially when a sonodynamically active agent had been administered to the
      mouse. Insonation with second-harmonic superimposition in combination with such
      administration may have potential use for selective tumor treatment.

PMID- 9000744
TI  - Anisotropy of the apparent frequency dependence of backscatter in formalin fixed
      human myocardium.
AB  - Measurements of the frequency dependence of ultrasonic backscatter are presented
      for specific angles of insonification for regions of infarcted and noninfarcted
      human myocardium. A 5-MHz transducer was used to insonify cylindrical cores taken
      from 7 noninfarcted regions and 12 infarcted regions of the left ventricular free
      wall of 6 formalin-fixed human hearts explanted because of ischemic
      cardiomyopathy. The dependence of apparent (uncompensated for diffraction effects
      and attenuation) backscatter on frequency was approximated by a power-law
      dependence, magnitude of B(f)2 = afn. Under ideal conditions in a lossless
      medium, the effect of not compensating for the effects of diffraction and
      attenuation leads to the value of n to be 2.0 for Rayleigh scatterers while the
      frequency dependence of the fully compensated backscatter coefficient would be
      f4. The value of n was determined over the frequency range, 3-7 MHz. Both
      nonifarcted and infarcted myocardium exhibited anisotropy of the frequency
      dependence of backscatter, with maxima occurring at angles that were
      perpendicular to the predominant myofiber direction and minima when parallel to
      the fibers. Perpendicular insonification yielded results for n of 1.8 +/- 0.1 for
      noninfarcted myocardium and 1.2 +/- 0.1 for infarcted myocardium while parallel
      insonification yielded results of 0.4 +/- 0.1 for noninfarcted and 0.0 +/- 0.1
      for infarcted myocardium. The functional form of the angle-dependent backscatter
      is similar for both noninfarcted and infarcted myocardium, although the frequency
      dependence is clearly different for both tissue states for all angles of
      insonification. The results of this study indicate that the anisotropy of the
      frequency dependence of backscatter may play a significant role in ultrasonic
      imaging and is an important consideration for ultrasonic tissue characterization
      in myocardium.

PMID- 9000746
TI  - Mechanisms of vocal production in budgerigars (Melopsittacus undulatus).
AB  - Songbirds vocalizing in helium show a change in the spectral quality of their
      vocalizations. This effect is due to an increase in the speed of sound in helium
      that in turn alters the resonance properties of the vocal tract. Here, this
      approach is extended to a psittacine, the budgerigar (Melopsittacus undulatus),
      whose syringeal anatomy and innervation differ from that of a songbird. Contact
      calls from birds vocalizing in heliox (70/30 helium/oxygen environment) showed an
      overall increase in the amount of energy at frequencies above the fundamental,
      slight changes in the frequency of the fundamental and harmonics, and some change
      in the level of harmonics. Calls produced by a syringeally denervated bird showed
      more dramatic changes. Recordings from live birds were compared with sounds
      produced by various simple "artificial" tracheal and syringeal models. Results
      suggest that budgerigars produce contact calls using the syringeal membranes as a
      unitary sound source which produces acoustic energy in a narrow frequency band
      whose fundamental frequency is matched to the resonant frequency of the trachea.
      The syrinx is not normally coupled to the tracheal resonator, and resonances
      probably play only a minor role in shaping the spectrum of contact calls.

PMID- 9000747
TI  - Hearing deficits measured in some Tursiops truncatus, and discovery of a
      deaf/mute dolphin.
AB  - Eight bottlenose dolphins Tursiops truncatus (four male, four female) were
      trained to respond to 100-ms tones. Three male dolphins (ages 23, 26, and 34)
      exhibited hearing disability at four higher frequencies-70, 80, 100, and 120 kHz
      even at 111-135 dB re: 1 microPa. Two females (ages 32 and 35) responded to all
      frequencies as did a male (age 7) and a female (age 11). One female (age 33)
      responded to all tones at 80 kHz and below; however, she failed to respond at 100
      or 120 kHz. One young female dolphin (age 9) exhibited no perception of sound to
      behavioral or electrophysiological tests. This young female was not only deaf,
      but mute. The dolphin was monitored periodically by hydrophone and daily by
      trainers (by ear in air) for 7 years until she was age 16. The animal never
      whistled or made echolocation pulses or made burst pulse sounds as other dolphins
      do.

PMID- 9000748
TI  - Rapid evolution of immunoglobulin superfamily C2 domains expressed in immune
      system cells.
AB  - To test the hypothesis that proteins expressed in cells of the vertebrate immune
      system evolve unusually rapidly, 107 orthologous immunoglobulin C2 domains were
      compared between human and murine rodent. The analysis showed that the rate of
      nonsynonymous (amino-acid-altering) nucleotide substitution in these domains was
      correlated with factors associated with protein structure and with breadth of
      tissue expression, as well as with the rate of synonymous substitution. However,
      when such factors were controlled for statistically, there remained a strong
      positive association between expression in the immune system and nonsynonymous
      rate, with the highest rates being seen in genes expressed in the immune system
      only. Certain immune system genes are known to be subject to positive selection
      favoring diversity at the amino acid level; most of these genes encode receptors
      that interact directly with foreign antigens. The observed acceleration of the
      rate of nonsynonymous evolution in C2 domains of immune system proteins may be
      explained by either (1) reduced constraint at the amino acid level on molecules
      interacting with immune system receptors that are themselves evolving rapidly due
      to positive diversifying selection or (2) positive selection favoring amino acid
      changes correlated with changes in the immune system receptors.

PMID- 9000749
TI  - Phylogenetic analysis of slippage-like sequence variation in the V4 rRNA
      expansion segment in tiger beetles (Cicindelidae).
AB  - Sequence variation in the middle part of the small-subunit rRNA was studied for
      representatives of the major groups in the family Cicindelidae (Coleoptera). All
      taxa exhibited a much expanded segment in variable region V4 compared to D.
      melanogaster. This expanded segment was not found in other groups of beetles,
      including three taxa in the closely related Carabidae. Secondary structure
      predictions indicate that the expanded segment folds into a single stem-loop
      structure in all taxa. Despite its structural conservation, the fragment differs
      strongly in primary sequence, even between closely related sister taxa. Several
      features of these sequences are consistent with slippage replication as the
      mechanism that has generated this sequence variation: the level of internal
      sequence repetition as measured by the relative simplicity factor (RSF), its
      variation in length between close relatives, and the strong nucleotide bias
      compared to the remainder of the gene. With few exceptions, there was also a
      correlation between sequence length and the level of sequence repetition,
      frequently interpreted as the result of slippage. Phylogenies inferred from the
      expansion segment were not consistent with existing hypotheses from other
      molecular data for the group. This indicates that DNA sequences in this region
      are not homologous throughout the entire Cicindelidae, but it leaves open the
      possibility that this expansion segment can be used for phylogeny reconstruction
      within subgroups. The implications of a phylogenetic approach to the
      understanding of slippage-like evolution are discussed.

PMID- 9000750
TI  - Molecular phylogeny of the springhare, Pedetes capensis, based on mitochondrial
      DNA sequences.
AB  - The phylogenetic position of the Pedetidae, represented by a single species
      Pedetes capensis, is controversial, reflecting in part the retention of both
      Hystricomorphous and Sciurognathous characteristics in this rodent. In an attempt
      to clarify the species evolutionary relationships, mtDNA gene sequences from 10
      rodent species (representing seven families) were analyzed using phenetic,
      parsimony, and maximum-likelihood methods of phylogenetic inference; the rabbit,
      Oryctolagus cuniculus (Order Lagomorpha), and cow, Bos taurus (Order
      Artiodactyla), were used as outgroups. Investigation of 714 base pairs of the
      protein-coding cytochrome b gene indicate strong base bias at the third codon
      position with significant rate heterogeneity evident between the three structural
      domains of this gene. Similar analyses conducted on 816 base pairs of the 12S
      rRNA gene revealed a transversion bias in the loop sections of all taxa. The
      cytochrome b gene sequences proved useful in resolving associations between
      closely related species but failed to produce consistent tree topologies at the
      family level. In contrast, phylogenetic analysis of the 12S rRNA gene resulted in
      strong support for the clustering of Pedetidae/Heteromyidae/Geomyidae and Muridae
      in one clade to the exclusion of the Hystricidae/Thryonomyidae and Sciuridae, a
      finding which is concordant with studies of rodent fetal membranes as well as
      reproductive and other anatomical features.

PMID- 9000752
TI  - Evolution of the AT-rich mitochondrial DNA of the root knot nematode, Meloidogyne
      hapla.
AB  - Mitochondrial DNA of the root knot nematode Meloidogyne hapla was investigated
      for intraspecific diversity and divergence from other parthenogenetic root knot
      nematodes. A 1,900-bp fragment containing COII, tRNAHis, 16S rRNA, ND3 and Cyt b
      genes has been cloned and sequenced from one individual and an 1,188-bp region
      within this region was sequenced from four other Australian isolates. M. hapla
      mtDNA is more than 80% AT-rich, like other Meloidogyne spp. Nucleotide diversity
      within M. hapla is some 10-fold higher than across three other parthenogenetic
      species of root-knot nematode (M. arenaria, M. javanica, and M. incognita),
      implying an earlier origin for M. hapla. Nucleotide divergence between M. hapla
      and its congener M. javanica is as great as that between Ascaris suum and
      Caenorhabditis elegans, members of different nematode subclasses, while amino
      acid sequence difference between Meloidogyne is more than twice as great. This is
      interpreted as an AT-bias-induced acceleration of the amino acid substitution
      rate, over and above saturation of nucleotide divergence in the strongly AT
      biased DNA, on three lines of evidence: (1) in conserved blocks in 16S rDNA
      congeneric Meloidogyne have no more differences than between A. suum and C.
      elegans; (2) the Meloidogyne lineage has more amino acid changes relative to the
      Ascaris/Caenorhabditis lineage with respect to four of five outgroups, the
      exceptional outgroup being the only species (Apis) as AT-rich as Meloidogyne; and
      (3) between the two Meloidogyne there are more first and second but fewer third
      codon position changes than between the other nematode species. M. hapla is also
      found to contain a 102-bp tandem repeat of at least 40 copies; a size,
      arrangement, and position the same as in M. javanica, but sequence comparisons
      did not demonstrate homology between the two repeats.

PMID- 9000751
TI  - Replication slippage may cause parallel evolution in the secondary structures of
      mitochondrial transfer RNAs.
AB  - Presence of the dihydrouridine (D) stem in the mitochondrial cysteine tRNA is
      unusually variable among lepidosaurian reptiles. Phylogenetic and comparative
      analyses of cysteine tRNA gene sequences identify eight parallel losses of the D
      stem, resulting in D-arm replacement loops. Sampling within the monophyletic
      Acrodonta provides no evidence for reversal. Slipped-strand mispairing of
      noncontiguous repeated sequences during replication or direct replication
      slippage can explain repeats observed within cysteine tRNAs that contain a D-arm
      replacement loop. These two mechanisms involving replication slippage can account
      for the loss of the cysteine tRNA D-stem in several lepidosaurian lineages, and
      may represent general mechanisms by which the secondary structures of
      mitochondrial tRNAs are altered.

PMID- 9000753
TI  - Evolution of the Sry genes.
AB  - Existing DNA sequence data on the Sry gene, the mammalian sex-determining locus
      in the Y chromosome, were analyzed for primates, rodents, and bovids. In all
      three taxonomic groups, the terminal sequences evolved faster than the HMG (high
      mobility group) boxes, and this applies both to synonymous (Ks) and nonsynonymous
      (Ka) nucleotide substitutions. Similar intragenic correlation between synonymous
      and nonsynonymous substitution rates was not found either in other mammalian
      genes that contain a conservative box (Sox, Msx) or in the MADS-box genes of
      plants. The rate of nonsynonymous substitutions exceeds significantly that of
      synonymous substitutions in the terminal Sry sequences of apes. We did not find
      good support for the hypothesis that the high evolutionary rate of Sry would be
      associated with a promiscuous mating system.

PMID- 9000754
TI  - Molecular phylogeny of extant gymnosperms and seed plant evolution: analysis of
      nuclear 18S rRNA sequences.
AB  - To study the evolutionary relationships among the four living gymnosperm orders
      and the interfamilial relationships in each order, a set of 65 nuclear 18S rRNA
      sequences from ferns, gymnosperms, and angiosperms was analyzed using the
      neighbor-joining and maximum-parsimony methods. With Selaginella as the outgroup,
      the analysis strongly indicates that the seed plants form a monophyletic group
      with the ferns as a sister group. Within the seed plants the angiosperms are
      clearly a monophyletic group. Although the bootstrap support for the monophyly of
      the gymnosperm clade is moderate, the monophyly is further supported by its lack
      of angiosperm-specific indels. Within the gymnosperms there appear to be three
      monophyletic clades: Cycadales-Ginkgoales, Gnetales, and Coniferales. The cycad
      ginkgo clade is the earliest gymnosperm lineage. Given the strong support for the
      sister group relationship between Gnetales and Coniferales, it is unlikely that
      Gnetales is a sister group of the angiosperms, contrary to the view of many plant
      taxonomists. Within Coniferales, Pinaceae is monophyletic and basal to the
      remaining conifer families, among which there are three monophyletic clades:
      Phyllocladaceae-Podocarpaceae, Araucariaceae, and Sciadopityaceae-Taxaceae
      Cephalotaxaceae-Taxodiacea e-Cupressaceae. Within the latter clade,
      Sciadopityaceae may be an outgroup to the other four families. Among the
      angiosperms, no significant cluster at the level of subclass was found, but there
      was evidence that Nymphaeaceae branched off first. Within the remaining
      angiosperms, the monocots included in this study are nested and form a
      monophyletic group. This study attests to the utility of nuclear 18S rRNA
      sequences in addressing relationships among living gymnosperms. Considerable
      variation in substitution rates was observed among the ferns and seed plants.

PMID- 9000755
TI  - Phylogenetic analysis of a retrotransposon with implications for strong
      evolutionary constraints on reverse transcriptase.
AB  - This study examines the evolutionary dynamics of a retrotransposon in a group of
      parasitoid wasps. A region containing the reverse transcriptase (RT) domain was
      sequenced for 43 elements from the genomes of nine different wasp species.
      Phylogenetic analysis of the elements revealed concordance with taxonomic
      classification of the host species, and the pattern was consistent with that
      expected for vertical transmission of a multicopy element during differentiation
      of the species. Twenty-three of the 43 elements had comparable intact open
      reading frames in the amplified region, and these were used in an analysis of
      evolutionary constraint on the amino acid sequence. As previously documented for
      retroelements, closely related elements exhibited nearly equal substitution rates
      at nonsynonymous and synonymous sites, but relative nonsynonymous substitution
      rates decreased as increasingly divergent elements were compared. A statistical
      test indicated that the decrease was not due to saturation of weakly selected
      sites. The pattern is most likely caused by a "pseudogene effect." Individual
      elements are not subject to purifying selection, and therefore, synonymous and
      nonsynonymous substitutions accumulate at equal rates. Comparisons among closely
      related elements are influenced strongly by this pseudogene evolution, whereas
      comparisons among distantly related elements reveal selection on the actively
      replicating lineages connecting the elements. These distant comparisons more
      accurately reflect the constraints on the amino acid sequence, and the
      comparisons among elements in this study indicated strong constraints on RT.

PMID- 9000758
TI  - How often do wrong models produce better phylogenies?

PMID- 9000756
TI  - Persistent nuclear ribosomal DNA sequence polymorphism in the Amelanchier agamic
      complex (Rosaceae).
AB  - Individual plants of several Amelanchier taxa contain many polymorphic nucleotide
      sites in the internal transcribed spacers (ITS) of nuclear ribosomal DNA (nrDNA).
      This polymorphism is unusual because it is not recent in origin and thus has
      resisted homogenization by concerted evolution. Amelanchier ITS sequence
      polymorphism is hypothesized to be the result of gene flow between two major
      North American clades resolved by phylogenetic analysis of ITS sequences. Western
      North American species plus A. humilis and A. sanguinea of eastern North America
      form one clade (A), and the remaining eastern North American Amelanchier make up
      clade B. Five eastern North American taxa are polymorphic at many of the
      nucleotide sites where clades A and B have diverged and are thought to be of
      hybrid origin, with A. humilis or A. sanguinea as one parent and various members
      of clade B as the other parent. Morphological evidence suggests that A. humilis
      is one of the parents of one of the polymorphic taxa, a microspecies that we
      refer to informally as A. "erecta." Sequences of 21 cloned copies of the ITS1
      5.8S gene-ITS2 region from one A. "erecta" individual are identical to A. humilis
      sequence or to the clade B consensus sequence, or they are apparent recombinants
      of A. humilis and clade B ITS repeats. Amelanchier "erecta" and another
      polymorphic taxon are suspected to be relatively old because both grow several
      hundred kilometers beyond the range of one of their parents. ITS sequence
      polymorphisms have apparently persisted in these two taxa perhaps because of
      polyploidy and/or agamospermy (asexual seed production), which are prevalent in
      the genus.

PMID- 9000757
TI  - Two novel gene orders and the role of light-strand replication in rearrangement
      of the vertebrate mitochondrial genome.
AB  - Two novel mitochondrial gene arrangements are identified in an agamid lizard and
      a ranid frog. Statistical tests incorporating phylogeny indicate a link between
      novel vertebrate mitochondrial gene orders and movement of the origin of light
      strand replication. A mechanism involving errors in light-strand replication and
      tandem duplication of genes is proposed for rearrangement of vertebrate
      mitochondrial genes. A second mechanism involving small direct repeats also is
      identified. These mechanisms implicate gene order as a reliable phylogenetic
      character. Shifts in gene order define major lineages without evidence of
      parallelism or reversal. The loss of the origin of light-strand replication from
      its typical vertebrate position evolves in parallel and, therefore, is a less
      reliable phylogenetic character. Gene junctions also evolve in parallel.
      Sequencing across multigenic regions, in particular transfer RNA genes, should be
      a major focus of future systematic studies to locate novel gene orders and to
      provide a better understanding of the evolution of the vertebrate mitochondrial
      genome.

PMID- 9000759
TI  - The evolution of strand-specific compositional bias. A case study in the
      Hymenopteran mitochondrial 16S rRNA gene.

PMID- 9000761
TI  - Beating bacteria. New ways to fend off antibiotic-resistant pathogens.

PMID- 9000760
TI  - Parallel molecular evolution of deletions and nonsense mutations in bacteriophage
      T7.

PMID- 9000762
TI  - Immunotherapy for cocaine addiction.

PMID- 9000763
TI  - Why and how bacteria communicate.

PMID- 9000764
TI  - The benefits and ethics of animal research.

PMID- 9000765
TI  - Animal research is wasteful and misleading.

PMID- 9000766
TI  - Animal research is vital to medicine.

PMID- 9000767
TI  - Trends in animal research.

PMID- 9000768
TI  - Working knowledge. Arthroscopoic surgery.

PMID- 9000770
TI  - Therapeutic play.

PMID- 9000771
TI  - Therapeutic play.

PMID- 9000769
TI  - Combined drug therapy debate (continued)

PMID- 9000773
TI  - Case puzzles and research designs.

PMID- 9000774
TI  - Naltrexone for alcohol abuse.

PMID- 9000775
TI  - Sertraline in PDD.

PMID- 9000776
TI  - Pediatric sleep disorders: a review of the past 10 years.
AB  - OBJECTIVE: To provide a 10-year review of pediatric sleep disorders medicine.
      METHOD: DSM-IV is used to organize the presentation from a developmental
      perspective. RESULTS: Pediatric sleep disorders can be subdivided into four broad
      categories: Primary Sleep Disorders that include two subcategories, Dyssomnias
      and Parasomnias; Sleep Disorder Related to Another Mental Disorder; Sleep
      Disorder Due to a General Medical Condition; and Substance-Induced Sleep
      Disorder. Behavioral and supportive methods of treatment remain the most useful
      methods for treating primary sleep disorders in childhood.

PMID- 9000777
TI  - Is ADHD a risk factor for psychoactive substance use disorders? Findings from a
      four-year prospective follow-up study.
AB  - OBJECTIVE: To evaluate whether attention-deficit hyperactivity disorder (ADHD) is
      a risk factor for psychoactive substance use disorders (PSUD), attending to
      issues of psychiatric comorbidity, family history, and adversity. METHOD: Using
      assessments from multiple domains, the authors examined 140 ADHD and 120 normal
      control subjects at baseline and 4 years later. Drug and alcohol abuse and
      dependence were operationally defined. RESULTS: No differences were detected in
      the rates of alcohol or drug abuse or dependence or in the rates of abuse of
      individual substances between the groups; both ADHD and control probands had a
      15% rate of PSUD. Conduct and bipolar disorders predicted PSUD, independently of
      ADHD status. Family history of substance dependence and antisocial disorders was
      associated with PSUD in controls but less clearly so in ADHD probands. Family
      history of ADHD was not associated with risk for PSUD. ADHD probands had a
      significantly shorter time period between the onsets of abuse and dependence
      compared with controls (1.2 years versus 3 years, p < .01). CONCLUSIONS:
      Adolescents with and without ADHD had a similar risk for PSUD that was mediated
      by conduct and bipolar disorder. Since the risk for PSUD has been shown to be
      elevated in adults with ADHD when compared with controls, a sharp increase in
      PSUD is to be expected in grown-up ADHD children during the transition from
      adolescence to adulthood.

PMID- 9000778
TI  - Prevalence and implications of attention-deficit hyperactivity disorder among
      adolescents in treatment for substance abuse.
AB  - OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is overrepresented
      among adults and adolescents in treatment for substance abuse. This study was
      designed to assess the prevalence of ADHD and to elucidate differences among
      adolescent substance abusers relative to ADHD symptomatology. METHOD: The Wender
      Utah Rating Scale and the Self-Evaluation (Teenager's) Self-Report were used to
      evaluate childhood history of ADHD and current symptoms, respectively, and the
      Child Attention Problems Scale was completed by treatment program clinicians. A
      quantitative substance use history and a subjective substance use interview were
      also administered. RESULTS: A total of 50% of 14 females and 16 males, ranging in
      age from 14 to 19, met study criteria for ADHD. ADHD subjects began drug use at
      an earlier age, had more severe substance abuse, and had a more negative self
      image prior to drug use and improved self-image with drug use. They experienced
      more negative affective responses related to substance use and more drug craving
      and attentional difficulties in treatment than control subjects. CONCLUSIONS: The
      results support a substantial comorbidity of ADHD among adolescent substance
      abusers, with indications of drug use for self-medication. Counseling for ADHD
      and medication may be indicated to improve treatment outcome and future
      functioning.

PMID- 9000779
TI  - ADHD is associated with early initiation of cigarette smoking in children and
      adolescents.
AB  - OBJECTIVE: The association between attention-deficit hyperactivity disorder
      (ADHD) and cigarette smoking in children and adolescents was evaluated. METHOD:
      Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n = 128) and non-ADHD
      comparison boys (n = 109) followed prospectively for 4 years into mid
      adolescence. Information on cigarette smoking was obtained in a standardized
      manner blind to the proband's clinical status. Cox proportional hazard models
      were used to predict cigarette smoking at follow-up using baseline
      characteristics as predictors. RESULTS: ADHD was a significant predictor of
      cigarette smoking at follow-up into mid-adolescence. Our findings also revealed
      that ADHD was associated with an early initiation of cigarette smoking. This was
      the case even after controlling for socioeconomic status, IQ, and psychiatric
      comorbidity. In addition, among children with ADHD, there was a significant
      positive association between cigarette smoking and conduct, major depressive, and
      anxiety disorders. CONCLUSIONS: ADHD, particularly the comorbid subtype, is a
      significant risk factor for early initiation of cigarette smoking in children and
      adolescents. Considering the prevalence and early childhood onset of ADHD, these
      findings highlight the importance of smoking prevention and cessation programs
      for children and adolescents with ADHD.

PMID- 9000781
TI  - Does PTSD transcend cultural barriers? A study from the Khmer Adolescent Refugee
      Project.
AB  - OBJECTIVE: To determine whether the factor structure of the posttraumatic stress
      disorder (PTSD) syndrome in Cambodian refugee youth resembles earlier reported
      factor studies in Caucasian samples. METHOD: 194 Khmer adolescent refugees who
      reported prior significant trauma (most of it massive war trauma as children)
      were administered the PTSD module of the Diagnostic interview for Children and
      Adolescents, as part of an epidemiological study on the effects of war on this
      group of refugees. RESULTS: The following four factors were found: arousal,
      avoidance, intrusion, and numbing. A confirmatory factor analysis using data from
      the parents of this sample yielded a good fit for the four-factor solution based
      on the youth data. CONCLUSIONS: The four-factor solution from this sample
      resembled earlier studies on traumatized Caucasian and African-American adults.
      These results lend further credibility to the veracity of this diagnosis with
      refugee samples. PTSD as a result of prior war trauma appears to surmount the
      barriers of culture and language in this sample.

PMID- 9000780
TI  - Case study: adverse effects of smoking marijuana while receiving tricyclic
      antidepressants.
AB  - Increasingly, children and adolescents are being treated for underlying
      psychopathology commonly associated with the psychoactive substance use
      disorders. Despite this apparent increase in using medication, little is known
      about the interaction of drugs of abuse with the psychotropic medications. The
      authors describe four cases of male adolescents aged 15 to 18 years being treated
      with a tricyclic antidepressant for attention-deficit hyperactivity disorder who
      manifested transient cognitive changes, delirium, and tachycardia after smoking
      marijuana.

PMID- 9000782
TI  - Acceptability of the Conners Parent Rating Scale and Child Behavior Checklist to
      Dakotan/Lakotan parents.
AB  - OBJECTIVE: The objective of this pilot study was to determine how Dakotan/Lakotan
      parents view the Conners Parent Rating Scale (CPRS) and Child Behavior Checklist
      (CBCL). METHOD: Using a focus group methodology, four discussion groups were held
      in different sites across South Dakota where the CPRS and CBCL were in clinical
      use. RESULTS: Only two questions on each form were incomprehensible to these
      Dakotan/Lakotan parents. Other questions were hard to answer because certain
      questions contained implicit dominant cultural values that did not take into
      account Dakotan/Lakotan cultural values or traditions, or the questions were hard
      to answer because Dakotan/Lakotan believed their responses could or would be
      misunderstood by members of the dominant culture who did not understand
      Dakotan/Lakotan style or customs. CONCLUSIONS: The CPRS and CBCL were generally
      acceptable to Dakotan/Lakotan parents. Clinicians could make several statements
      to Native parents that would improve cultural acceptability.

PMID- 9000783
TI  - Child survivors of suicide: psychosocial characteristics.
AB  - OBJECTIVE: To describe psychosocial characteristics of children and young
      adolescents who experienced the recent suicidal death of a parent or sibling.
      METHOD: Sixteen families with children aged 5 years to 14 years and who
      experienced the suicidal death of a relative on average within the year of
      research assessment were recruited from the community and evaluated with standard
      research instruments for levels of children's psychiatric symptoms and social
      adjustment. RESULTS: Child survivors of suicide had a higher rate of
      internalizing symptoms and poorer school adjustments than a standard community
      sample. Twenty-five percent of the families had children who reported clinically
      significant symptoms of depression. Approximately 40% of the families included
      children who reported at least moderate symptoms of posttraumatic stress.
      Approximately 31% of families had at least one child who reported suicidal
      ideation, but no child reported a suicide attempt. Significant associations were
      identified between psychosocial features of the children and parental psychiatric
      symptoms and stressful life events. CONCLUSION: Child survivors of suicide are at
      risk for psychiatric symptoms and social maladjustment which require early
      identification and preventive intervention to minimize risk for more extensive
      psychosocial morbidity.

PMID- 9000784
TI  - Adolescent suicidality in urban minorities and its relationship to conduct
      disorders, depression, and separation anxiety.
AB  - OBJECTIVE: This research investigates personality variables--aggression and
      disorders of conduct, depression, and separation anxiety--mediating suicidal
      behavior in psychiatrically hospitalized urban minority adolescents. METHOD: Four
      matched groups of 26 subjects (N = 104) participated: suicidal adolescents with,
      and suicidal adolescents without, a conduct disorder diagnosis, nonsuicidal
      adolescents with a conduct disorder diagnosis, and a nonpsychiatric control
      group. Subjects were assessed with three dimensions from the Epigenetic
      Assessment Rating System (EARS), the Children's Depression Inventory (CDI), and
      the Separation Anxiety Test (SAT). RESULTS: A conduct disorder diagnosis was
      related to lower modal EARS scores. The EARS and the CDI each identified a
      different subset of suicidal adolescents. Adolescents with lower modal EARS
      scores exhibited greater reactivity to separation experiences on the SAT.
      CONCLUSION: Relying on depressive symptomatology to identify suicidality
      overlooks a majority of at-risk adolescents. Structural personality variables as
      measured by the EARS identify and distinguish subsets of suicidal adolescents.

PMID- 9000785
TI  - Suicidal adolescents after hospitalization: parent and family impacts on
      treatment follow-through.
AB  - OBJECTIVE: To help determine optimal strategies for treating suicidal
      adolescents, the authors studied family predictors of compliance with recommended
      psychotropic medication monitoring, individual therapy, and parent
      guidance/family therapy sessions. METHOD: Sixty-six hospitalized, suicidal
      adolescents participated in a comprehensive diagnostic evaluation and
      depression/suicidality assessment. Family/parental assessment measures were the
      Family Assessment Device, Social Adjustment Inventory for Children and
      Adolescents (parent-adolescent subscales), Symptom Checklist-90-Revised, and
      Social Adjustment Scale-Self Report. Follow-up evaluation, 6 months
      posthospitalization, consisted of structured telephone interviews assessing
      treatment follow-through. RESULTS: Compliance with recommended medication follow
      up (66.7%) and individual therapy (50.8%) was better than compliance with parent
      guidance/family therapy (33.3%) sessions. The most dysfunctional families and
      those with the least involved/affectionate father-adolescent relationships had
      the poorest follow-through with parent guidance/family therapy. Mothers'
      depressive and paranoid symptoms were linked with less adolescent individual
      therapy and family therapy follow-through. Mothers' hostility was associated with
      less medication follow-up. CONCLUSIONS: Follow-through was best for medication
      and individual therapy. Multiple family/parental predictors of poor follow
      through suggest the need for alternative or supplemental treatment strategies.

PMID- 9000786
TI  - Traumatic brain injury in children and adolescents: psychiatric disorders in the
      first three months.
AB  - OBJECTIVE: To assess predictive factors of psychiatric outcome in the first 3
      months after traumatic brain injury (TBI) in children and adolescents. METHOD:
      Subjects were children aged 6 to 14 years at the time they were hospitalized
      after TBI. The study used a prospective follow-up design. Assessments of
      preinjury psychiatric, behavioral, adaptive functioning, family functioning, and
      family psychiatric history status were conducted. Severity of injury was assessed
      by standard clinical scales and neuroimaging was analyzed. The outcome measure
      was the development of a psychiatric disorder, never before present ("novel") in
      a subject during the first 3 months after the TBI. RESULTS: Fifty subjects
      enrolled, and the analyses focused on 37 subjects followed up at 3 months.
      Increasing severity of injury, presence of a lifetime psychiatric disorder,
      family psychiatric history, family dysfunction, and lower socioeconomic
      class/preinjury intellectual function predicted the development of a "novel"
      psychiatric disorder in the first 3 months of follow-up. CONCLUSIONS: These data
      suggest that there are children, identifiable through clinical assessment, at
      increased risk for development of psychiatric disorders in the first 3 months
      after TBI.

PMID- 9000787
TI  - Utility of thyroid function screening in adolescent psychiatric inpatients.
AB  - OBJECTIVE: Thyroid function abnormalities have been associated with psychiatric
      symptoms. This study examines the utility of thyroid screening among adolescent
      psychiatric inpatients. METHOD: A retrospective chart review of 196 first-time
      admissions to an adolescent psychiatric unit was conducted. Charts were screened
      for demographics, presence/absence of thyroid function testing, history of
      thyroid disease, medication/illicit substance use, and other factors of influence
      on thyroid testing. Thyroid test results were reviewed for abnormalities.
      RESULTS: Thyroid function testing was conducted in 150 of the 196 admissions.
      Fifty-two patients had abnormalities, most of which were isolated abnormalities
      of thyroxine (T4) or triiodothyronine uptake (T3U). Laboratory diagnosis of
      hyperthyroidism and mild hypothyroidism was met by two and eight patients,
      respectively; five had profiles that were normal upon subsequent testing 1 week
      later. None of the patients was symptomatic, and none required thyroid
      supplementation or antithyroid medications. Gender differences in T4 and T3U were
      noted, and age was positively correlated with T3U. CONCLUSIONS: Thyroid function
      tests may be spuriously abnormal in routine screening of newly admitted
      psychiatric patients. Routine thyroid screening among adolescent psychiatric
      inpatients is unwarranted except in patients who display physical signs or
      symptoms suggestive of thyroid disease.

PMID- 9000788
TI  - Case study: Ganser syndrome in children and adolescents.
AB  - Six cases of the Ganser syndrome have been previously described in the literature
      and are reviewed here. They are imperfect representations of the originally
      described syndrome. This article describes a case of the Ganser syndrome in a 12
      year-old boy who, after a mild head injury, presented with three of four of the
      core symptoms. The nature of the Ganser syndrome remains unclear, but this case
      study highlights dissociation and abnormal illness behavior as being important in
      the production of the symptoms. Classically the course is short-lived, although
      this report raises the possibilities of a much more chronic course.

PMID- 9000789
TI  - Domestic violence and children: prevalence and risk in five major U.S. cities.
AB  - OBJECTIVE: Children witnessing domestic violence is a major national concern. The
      present study provided data on the prevalence of children's exposure to
      substantiated cases of adult female assaults in five U.S. cities. METHOD: Data
      for this study were drawn from the Spouse Assault Replication Program (SARP)
      database, collected from police officers and female victims of misdemeanor
      domestic violence. In addition, household demographic data and data on
      involvement of children in the violent incidents were collected. Data from the
      SARP households were compared with census data from each city. RESULTS: Results
      indicated that children were disproportionately present in households with
      domestic violence and that young children were disproportionately represented
      among these children. Moreover, these children were exposed to excessive levels
      of additional developmental risk factors and they were involved in the incidents
      to varying degrees. CONCLUSIONS: These findings underscore the importance of
      establishing a more rigorous interdisciplinary, scientific research agenda to
      inform assessment and treatment efforts for a very vulnerable group of children
      who witness domestic violence, children aged 0 through 5 years.

PMID- 9000790
TI  - Psychosocial characteristics of physically abused children and adolescents.
AB  - OBJECTIVE: To examine the association between physical abuse and selected
      psychosocial measures in a community-based probability sample of children and
      adolescents. METHOD: A sample of 9- through 17-year-olds (N = 665) and their
      caretakers in New York State and Puerto Rico were interviewed in the Methods for
      the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study.
      Assessments included the Columbia Impairment Scale, the Instrumental and Social
      Competence Scale, the Diagnostic Interview Schedule for Children, the Peabody
      Picture Vocabulary Test, and questions regarding physical abuse. Regression
      analyses were conducted controlling for family income, family psychiatric
      history, perinatal problems, physical health, and sexual abuse. RESULTS: A
      history of physical abuse was reported in 172 (25.9%) of the sample. It was
      significantly associated with global impairment, poor social competence, major
      depression, conduct disorder, oppositional defiant disorder, agoraphobia,
      overanxious disorder, and generalized anxiety disorder but not with suicidality,
      school grades, or receptive language ability. CONCLUSION: A community probability
      sample of children and adolescents demonstrated significant associations between
      physical abuse and psychopathology, after controlling for potential confounders.
      This supports comprehensive screening for psychopathology among physically abused
      children and for physical abuse among those with psychopathology. Interventions
      aimed at improving social competence may be indicated.

PMID- 9000792
TI  - Future gazing and leadership.

PMID- 9000794
TI  - Dental managed care in the context of ethics. The officers and regents of the
      American College of Dentists.

PMID- 9000791
TI  - AACAP official action. Practice parameters for the assessment and treatment of
      children and adolescents with bipolar disorder.
AB  - These practice parameters describe the assessment and treatment of early-onset
      bipolar disorder based on scientific evidence regarding diagnosis and effective
      treatment and on the current state of clinical practice. Given the paucity of
      research on bipolar disorder in children and adolescents, many of the treatment
      recommendations are drawn from the adult literature. Although the same diagnostic
      criteria are used as for adults, youth may differ with regard to the
      developmental presentation of symptoms and comorbid psychiatric disorders.
      Treatment involves the combination of pharmacotherapy and adjunctive psychosocial
      interventions. Antimanic agents (primarily lithium or valproic acid) are the
      mainstays of pharmacotherapy. The treatment focuses on (1) amelioration of acute
      symptoms; (2) the prevention of relapse; (3) the reduction of long-term
      morbidity; and (4) the promotion of long-term growth and development. These
      parameters were approved by Council of the American Academy of Child and
      Adolescent Psychiatry on June 5, 1996.

PMID- 9000793
TI  - The most respected voice in dentistry. ACD president-elect's address. September
      27, 1996. Orlando, Florida.

PMID- 9000796
TI  - Virtue theory and a dental managed care case.

PMID- 9000795
TI  - Principles of dental ethics and the ethics of managed care.

PMID- 9000797
TI  - Casuistry in dental ethics: a case for cases.

PMID- 9000798
TI  - Ethical analysis from the perspective of rational self-interest.

PMID- 9000799
TI  - Looking for virtue in a virtuous society--discursive ethics and dental managed
      care.

PMID- 9000800
TI  - Moral problem-solving in managed care.

PMID- 9000801
TI  - A moral development perspective applied to a case on dental managed care.

PMID- 9000802
TI  - Professional Ethics in Dentistry Network (PEDNET).

PMID- 9000803
TI  - The first P--product.

PMID- 9000804
TI  - Molecular basis of cis-diamminedichloroplatinum(II) resistance: a review.
AB  - Cisplatin is one of the most widely used chemotherapeutic agents. However, at
      sublethal concentrations, resistance of cells to the drug occasionally arise,
      which greatly limits its effectiveness in cancer therapy. In this review, the
      mechanisms of acquired resistance to cisplatin are elucidated. Numerous
      mechanisms potentially contributing to clinical cisplatin resistance have been
      identified, including changes in membrane permeability, detoxification pathways
      and the ability to remove cytotoxic lesions from DNA. Changes triggered by
      cisplatin selection in the resistant phenotype involve a secondary layer of
      complexity that may include alterations in: 1) oncogene and protein kinase signal
      transduction pathways: 2) growth factor and hormone responsiveness; 3) chromosome
      structure and gene expression; 4) ion transport; 5) thymidilate metabolism; and
      6) nutrient transport and utilization. It is likely that all of these changes are
      part of an interconnected, multifarious response to cisplatin selection. Which of
      these biochemical changes come to predominate may depend on the type of cell and,
      particularly, on the selection procedure. In general, chronic, long-term exposure
      to increasing concentrations of cisplatin seems to lead to permanent elevations
      in the levels of the nucleophiles glutathione and metallothionein. Pulsed
      administration of cisplatin once a week leads to changes in folate metabolism and
      oncogene expression, while acute administration of cisplatin once a month leads
      to defects in drug accumulation. However, the environment of a tumor is
      remarkably different from the environment of tumor cells in culture (nutrient,
      growth factor and hormone availability; pH; intercellular communication; and
      oxygenation state). In addition, the various oncogene and protein kinase signal
      transduction pathways are likely to be featured differently in these two
      environments. In contrast to the sublethal concentrations of cisplatin used in
      the selection of resistance phenotype a lethal concentration of cisplatin may
      generate DNA adducts in cells, which cause G2 arrest of the cell cycle and
      subsequently lead to apoptosis. Recently, excitement in this field arose from the
      findings that cisplatin-DNA adducts bind several cellular proteins, termed
      cisplatin-damaged-DNA recognition proteins, including some that enhance survival
      of the cells by mediating DNA repair and others that hasten their death by
      conferring sensitivity to the drug.

PMID- 9000805
TI  - Emergency use of extracorporeal membrane oxygenation in a patient with post
      cardiotomy myocardial stunning.
AB  - Myocardial stunning refers to reversible postischemic myocardial dysfunction
      persisting after reperfusion. We report a patient who presented with
      biventricular failure, but exhibited neither definite electrocardiographic change
      nor elevation of serum cardiac enzyme levels in the post-cardiotomy period. The
      presentation was indicative of myocardial stunning. The patient's hemodynamics
      could not be maintained even with infusion of high doses of catecholamines.
      Extracorporeal membrane oxygenation successfully restored myocardial function. In
      conclusion, when the hemodynamic status of a patient with myocardial stunning
      cannot be maintained with inotropic agents, extracorporeal membrane oxygenation
      should be considered.

PMID- 9000806
TI  - SS-A/Ro antibodies in Chinese patients with systemic lupus erythematosus and
      Sjogren's syndrome.
AB  - Serum from 53 patients with systemic lupus erythematosus (SLE) and 23 patients
      with primary Sjogren's syndrome (SS) were studied for anti-52-kDa SS-A/Ro, anti
      60-kDa SS-A/Ro, and anti-SS-B/La antibodies by immunoblotting and enzyme-linked
      immunosorbent assay (ELISA). By immunoblotting, anti-SS-A/Ro was detected in 16
      (30%) patients with SLE and 17 (74%) patients with SS. Anti-SS-B/La was detected
      in 22 (41%) patients with SLE and 15 (65%) patients with SS. Serum from 14 of the
      16 SLE patients with anti-SS-A/Ro reacted with the 60-kDa protein and 15 serum
      samples from these patients recognized the 52-kDa protein. Serum with anti-60-kDa
      SS-A/Ro alone was not found. Serum from all of the 17 SS patients with anti-SS
      A/Ro reacted with the 52-kDa protein, whereas serum from only two of these
      patients recognized the 60-kDa protein. By ELISA, the frequency of anti-SS-A/Ro
      (antibodies to the 60-kDa and/or 52-kDa of SS-A/Ro proteins) in patients with SLE
      and SS was 43/53 (81%) and 15/23 (65%), respectively. Anti-48-kDa SS-B/La was
      found in 28% and 48% of SLE and SS patients, respectively. Serum from 77% of SLE
      patients and 48% of SS patients reacted with the 60-kDa SS-A/Ro protein. Serum
      from 45% of SLE patients and 52% of SS patients reacted with the 52-kDa SS-A/Ro
      protein. Patients with SLE had significantly higher titers of antibodies to 60
      kDa SS-A/Ro compared with patients with SS. Anti-SS-A/Ro and anti-SS-B/La are
      common in both SLE and SS. The different reactivities of anti-52-kDa and anti-60
      kDa antibodies in serum from patients with SLE and SS may represent differences
      in conformation-dependent epitopes of SS-A/Ro autoantigens.

PMID- 9000807
TI  - Frequency and distribution of chromosomal integration sites of the Epstein-Barr
      virus genome.
AB  - Human lymphocytes can be transformed in vitro by integration of the Epstein-Barr
      virus (EBV) into the host genome. To study whether integration sites are stable
      or changeable in the course of long-term cultivation, three EBV-transformed
      lymphoblastoid cell lines, along with positive control (Namalwa cell line) and
      negative control (noninfected lymphocytes) cells were studied. A biotinylated Bam
      H1WEBV-DNA fragment was used as the probe for fluorescence in situ hybridization
      to count the numbers and to localize the sites of integrated EBV-DNA. Among these
      cell lines, the percentage of cells with integrated signals varied from 58% to
      91%, with a mean of 1.43 to 2.66 signals per cell. No consistent tendency of
      increasing or decreasing number of signals was observed for the three cell lines
      harvested at four different cultivation intervals (86-204 days after infection).
      Although the integration was not site-specific, high frequencies of integration
      did occur in all three cell lines at the following chromosomal sites: 1p31, 1q31,
      2q32, 3q13, 6q24 and 7q31. Because there were multiple integration sites present,
      it was difficult to draw any conclusion on integration site stability.

PMID- 9000808
TI  - Clinical manifestations, microbiology and prognosis of 42 patients with
      necrotizing fasciitis.
AB  - Forty-two cases of necrotizing fasciitis (NF) surgically confirmed between
      January 1991 and October 1995 were retrospectively reviewed. This was done in
      order to describe the underlying diseases, clinical presentations, etiology and
      outcome of NF and to assess the prognostic value of a simplified severity scoring
      system. The system scores changes in consciousness status, body temperature,
      blood pressure and ventilation to determine the likely outcome of NF. Twenty-five
      men and 17 women with a median age of 51 years (range, 17-87 yr) were included.
      Diabetes mellitus (57.1%) was the most common underlying disease. The mean
      duration of symptoms before admission was 8 days (median, 7 d; range, 1-30 d).
      The extremities (66.7%) were most commonly involved. Initial clinical
      presentations within 48 hours of admission included skin erythema and swelling at
      the affected site (97.6%), pyrexia (61.9%), hypotension (33.3%), altered
      consciousness (28.6%), bullous lesions (26.2%) and crepitus (9.5%). The mean
      number of isolated pathogens was 1.8 (range, 0-6). Eight patients had mixed
      aerobic and anaerobic infections. The attributable case fatality rate was 23.8%.
      Higher severity score (> or = 4 points), hypotension, altered consciousness,
      respiratory failure requiring ventilator support, elevation of alanine
      aminotransferase levels > twofold, serum creatinine > 177 mumol/L,
      thrombocytopenia (< 100 x 10(9)/L), and worsening symptoms and signs within 48
      hours of admission were associated with higher fatality rates (p < 0.05).

PMID- 9000809
TI  - Clinical features of tuberculosis associated with HIV infection in Taiwan.
AB  - To understand the clinical characteristics and outcome of tuberculosis (TB) in
      patients with acquired immunodeficiency syndrome (AIDS) in Taiwan, we reviewed
      the medical records of 118 adult AIDS patients who were hospitalized at National
      Taiwan University Hospital between January 1988 and September 1995. Among them,
      29 (24.6%) had TB. The mean age of the AIDS patients with TB was 37 years (range,
      25-66 yr). Most patients were in the advanced stages of AIDS when human
      immunodeficiency virus (HIV) infection and/or TB were first diagnosed. The mean
      CD4+ lymphocyte count was 0.037 x 10(9)/L (range, 0-0.152 x 10(9)/L) at the time
      TB was diagnosed. There was no statistically significant difference in the mean
      CD4+ lymphocyte count between patients with isolated pulmonary TB and those with
      extrapulmonary involvement. Twenty-two patients (75.8%) had extrapulmonary TB
      with the most common site being the lymph nodes (72.7%). Clinical symptoms were
      nonspecific, and the chest physical examination was not helpful in the diagnosis.
      Acid-fast bacilli were detected in sputum smears from eight patients (36.4%). A
      primary tuberculosis pattern (hilar adenopathy, pleural effusion, middle or lower
      lobe infiltrates) in the chest radiographs was the most common radiologic finding
      (36.4%) in patients with pulmonary TB. The reactivation pattern (predominant
      upper-lobe infiltrates with or without cavitation) could only be found in cases
      of pulmonary TB without extrapulmonary involvement. Atypical patterns (diffuse
      interstitial infiltrates mimicking Pneumocystis carinii pneumonia or other
      patterns) and normal chest radiographs were noted in nearly one-third of the
      patients with pulmonary TB. A good response to antituberculosis drugs and a
      favorable outcome were demonstrated in the patients, except for two with drug
      resistant Mycobacterium tuberculosis infection. Early identification of TB in HIV
      infected patients requires clinical awareness of the unusual clinical
      presentations, especially among patients in the advanced stages of AIDS.

PMID- 9000810
TI  - Posterior bow and vanishing line signs in diagnosis of burst fractures of the
      spine on plain radiographs.
AB  - It is not uncommon to misdiagnose a burst fracture as a wedge compression
      fracture initially on plain film, resulting in a late progressive deformity and
      neurologic damage. The purpose of this study was to analyze the sensitivity,
      specificity and positive predictive value of plain radiographs in the diagnosis
      of thoracic and lumbar burst fractures using the posterior bow (PB) and vanishing
      line (VL) signs. Seven independent examiners, comprising three chief orthopedic
      residents, two radiologic third-year residents and two emergency attending
      physicians (orthopedists), randomly reviewed 26 sets of admission anteroposterior
      and lateral thoracolumbar spine radiographs taken in association with back
      injuries. They were asked to decide whether patients had a burst or a wedge
      compression fracture. All patients had computed tomography (CT) scans for
      diagnostic confirmation. The overall initial sensitivity using discriminant
      analysis in the diagnosis of burst fractures was 80%. This increased to 90% after
      the examiners were requested to use the PB and VL signs. The specificity
      decreased slightly from 75% to 71%, while the positive predictive value remained
      at 88%. Overdiagnosis of wedge compression fractures as burst fractures occurred,
      especially when the quality of the films was not ideal. We conclude that, with
      careful reading, the PB and VL signs help in identifying burst fractures on the
      initial plain film evaluation.

PMID- 9000811
TI  - Idiopathic hypereosinophilic syndrome with eosinophilic myositis, peripheral
      neuropathy and central nervous system involvement.
AB  - Idiopathic hypereosinophilic syndrome (HES) is a rare disorder marked by a
      sustained overproduction of eosinophils and a predilection for damage to multiple
      organ systems. Its neurologic involvement ranges from the central to the
      peripheral nervous system, and can be associated with eosinophilic myositis. We
      report a 68-year-old woman who had eosinophilia, eosinophilic dermatitis and
      eosinophilic pneumonia. She also suffered from numbness and weakness of the lower
      limbs. Because of long-lasting (> 6 mo) eosinophilia (> 1.5 x 10(9)/L) in the
      peripheral blood and the fact that no other underlying causes of eosinophilia and
      neurologic involvement could be identified, a diagnosis of idiopathic
      hypereosinophilic syndrome was made. The muscle biopsy showed infiltration of
      inflammatory cells, including a few eosinophils (Liu's stain). Magnetic resonance
      images, motor evoked potentials, somatosensory evoked potentials and nerve
      conduction velocities also showed abnormalities in the central and peripheral
      nervous systems. The pathogenesis and treatments of HES are discussed in this
      report.

PMID- 9000812
TI  - Rigid bronchoscopy and jet ventilation in an extremely low birthweight infant.
AB  - Until recently, rigid bronchoscopy was considered too risky for premature
      infants. We report a 658 g infant with life-threatening mediastinal shift due to
      right pulmonary atelectasis. Rigid bronchoscopy revealed tenacious mucous plugs
      in the right main bronchus. The collapsed lung was successfully reinflated after
      bronchial lavage with a rigid bronchoscope, with the help of intermittent high
      frequency jet ventilation (HFJV). The infant's mediastinal shift was reversed and
      the vital signs became stable. In our experience, rigid bronchoscopy combined
      with HFJV is a valuable diagnostic and therapeutic procedure for very small
      premature infants.

PMID- 9000813
TI  - Partial anomalous pulmonary venous drainage associated with intact atrial septum
      and pulmonary valve stenosis.
AB  - Partial anomalous pulmonary venous drainage (PAPVD) with an intact atrial septum
      is a very rare cardiovascular anomaly. Most PAPVD cases can be detected by
      echocardiographic scanning of the anomalous pulmonary venous connection. This
      paper describes an asymptomatic 6-year-old boy who was referred because of a
      heart murmur. An electrocardiogram and two-dimensional echocardiography revealed
      right heart volume overload. Mild pulmonary valve stenosis and an intact atrial
      septum were noted. In addition, color flow mapping demonstrated the right upper
      pulmonary vein connecting to the superior vena cava. This paper emphasizes that
      two-dimensional echocardiography in conjunction with color flow mapping is a
      valuable modality in the detection of anomalous pulmonary venous drainage.

PMID- 9000814
TI  - Ventrolateral thalamotomy for dyskinesia following levodopa therapy of
      Parkinson's disease.
AB  - We report a 65-year-old male parkinsonian patient who developed dominantly
      unilateral choreic movements over his right-side extremities after a daily dosage
      of up to 1,000 mg of carbidopa-levodopa (carbidopa 200 mg, levodopa 800 mg) for
      12 years. The disabling choreic movement appeared as a pattern of peak-dose
      dyskinesia and was so severe that he was unable to sit or stand still to suppress
      the involuntary movements. It started about 20 minutes after each dose of
      levodopa and lasted for about 2 hours. Although the dyskinesia could be reduced
      by decreasing the levodopa dosage, he could not tolerate the severe parkinsonian
      disabilities. The dyskinesia did not respond to baclofen, diazepam or clozapine.
      The chorea was successfully treated surgically using stereotactic left
      ventrolateral thalamotomy. This is an important treatment for patients with
      intractable dyskinesia after prolonged levodopa therapy.

PMID- 9000815
TI  - Clinical isolation of vancomycin-resistant Enterococcus faecalis in Taiwan.
AB  - We report the isolation of a vancomycin-resistant strain of Enterococcus
      faecalis, designated AH803, from a 76-year-old Taiwanese woman with pneumonia and
      bacteremia. This is the first documented clinical isolation of a vancomycin
      resistant enterococcus in Taiwan. AH803 was repeatedly isolated from sputum
      specimens of the patient. AH803 had a high level of vancomycin (minimal
      inhibitory concentration, MIC = 512 micrograms/mL) and gentamicin (MIC > 2,000
      micrograms/mL) resistance, but was susceptible to teicoplanin (MIC = 8
      micrograms/mL) and ampicillin (MIC = 2 micrograms/mL). AH803 was shown by
      polymerase chain reaction to have the vanA gene, but not the vanB gene. Despite
      treatment efforts, the patient's condition continued to deteriorate. She
      requested to be discharged, against medical advice. The patient died at home the
      following day after discharge.

PMID- 9000816
TI  - Laparoscopic surgery in urology.

PMID- 9000817
TI  - Gestational diabetes mellitus--screening in a developing country.
AB  - All gravid women attending the antenatal clinic of the department of Gynaecology
      Unit-II, Civil Hospital Karachi and unbooked cases presenting in labour from
      October, 1986 to December, 1993, were included in the study. On the basis of risk
      factors for diabetes mellitus (DM), they were divided into 3 groups. Women in
      Group-I had family history of DM, bad obstetric history, congenitally malformed
      babies, polyhydramnios, obesity and macrosomia. Group-II included women with
      pregnancy induced hypertension (PIH) abruptio placentae, age > 30 years and
      multiple pregnancy. Group-III comprised of the pregnant women with no risk
      factors for DM. Screening of 4497 subjects from the antenatal clinic was
      performed and DM was diagnosed in 211 (12%) in Group-I, 11 (3%) in Group-II and
      13 (0.6%) in Group III. Chi-square analysis demonstrated that frequency of DM was
      significantly higher (P < 0.001) in Group I and Group II as compared to Group
      III. Non-booked admissions numbered 7600, of these, DM was detected in 166 (20%)
      belonging to Groups-I and II, whereas, 38 (0.6%) were from Group-III. Screening
      was done by the O'Sullivan criteria. It was concluded that all pregnant women
      should be screened for DM. However, if financial constraints prevail, then women
      with high risk factors only should be subjected to screening.

PMID- 9000818
TI  - Serum proteins electrophoresis in infants and children.
AB  - Total serum proteins and its fractions were estimated in 468 infants and children
      from birth to 4 years in relation to age, sex and dietary pattern. The mean
      values of total serum proteins and its fractions showed some changes with age,
      especially in gamma globulins, which was high at birth and showed a decrease at
      the age of 3 months, after which it increased and attained an adult level at the
      age of 18 months. No difference was noted between the two sexes. Completely
      breast fed infants had a significantly higher protein and albumin levels at 3
      months than completely weaned infants but no such difference was observed in
      other protein fractions in the same age groups.

PMID- 9000819
TI  - Sero-prevalence of HIV: six years' experience at Shaikh Zayed Hospital, Lahore.
AB  - Sero-prevalence of HIV was tested among 16,170 individuals. They included 215
      patients with sexually transmitted diseases (STD), 77 I/V drug users, 21
      commercial sex workers, 987 patients on haemodialysis, 119 subjects referred for
      HIV testing, 12,482 voluntary blood donors, 360 ante-natal attenders, 73
      tuberculosis patients, 674 Pakistanis travelling abroad and 1162 persons who had
      received multiple blood transfusions. Ten persons were seropositive (0.06%). All
      of them came from the 119 subjects, suspected to be suffering from AIDS. The
      predominant mode of transmission was heterosexual (50%), blood transfusion (30%),
      homosexual (10%) and vertical (10%). All cases acquired infection outside the
      country. Comparisons have been made with other national studies.

PMID- 9000821
TI  - Percutaneous needle biopsy in exudative ascites.
AB  - Seventy-two patients with exudative ascites were subjected to percutaneous needle
      biopsy of peritoneum. The overall diagnostic yield was 64%, with the commonest
      finding being caseous granuloma (39%), followed by metastatic carcinoma (25%).
      The procedure was safe and easy to perform on the bed side. Peritoneal tissue was
      obtained in all cases, without any major complications.

PMID- 9000820
TI  - Open label trial of the efficacy and tolerability of Lamisil (Terbinafine) 500 mg
      once daily in the treatment of onychomycosis due to candida.
AB  - An open label trial of Lamisil (Terbinafine) 500 mg daily for 16 weeks was
      conducted on 20 patients with Onychomycosis due to candida. Of these, 15 patients
      could complete the trial. Total number of target nails infected was 21. The
      follow-up period was from 16 to 52 weeks. At 16 weeks, 71% cases showed clinical
      improvement and 67% had mycological cure. Thirty-three percent had complete cure
      at 52 weeks. The results show that Terbinafine is effective against candida but
      requires a longer duration of treatment. The drug was well tolerated.

PMID- 9000822
TI  - Parotid gland lipoma--a rare entity.

PMID- 9000823
TI  - Chorea--a presenting feature of giant cell arteritis.

PMID- 9000824
TI  - Antihistamines and their role in dermatology.

PMID- 9000825
TI  - Euthanasia: changing trends.

PMID- 9000826
TI  - Comparative study of diclofenac sodium and flurbiprofen in osteoarthritis.
AB  - A comparative study was conducted to evaluate the therapeutic efficacy of
      diclofenac sodium and flurbiprofen both non-steroidal anti-inflammatory drugs
      (NSAIDS) in osteoarthritis. Forty patients of either sex between the ages of 35
      60 years suffering from osteoarthritis of at least one knee joint minimum of
      eight weeks duration were included in the study. Diclofenac sodium exhibited
      better results by improving the signs and symptoms of osteoarthritis in both high
      and low doses compared to flurbiprofen. The adverse effects observed were similar
      in both groups.

PMID- 9000827
TI  - Blood lead levels in preschool children in Rawalpindi.
AB  - Blood lead levels were determined in preschool children residing in Urban areas
      of Rawalpindi city. Of 92 (50 males and 42 females) children aged one to 5 years
      were included in the study. Blood lead levels ranged from 7 micrograms/dl to 34
      micrograms/dl (mean 18.8 micrograms/dl). The mean lead levels were slightly
      higher in males (20.3 micrograms/dl) than in females (17.2 micrograms/dl) and
      over 90% children had lead levels above the acceptable limit of 10 micrograms/dl.
      Use of leaded petrol, contaminated surma, leaded paints and pica in children are
      common in our country and may lead to increased lead levels and appropriate
      measures should be taken to control this trend.

PMID- 9000828
TI  - Laryngeal involvement in pulmonary tuberculosis.
AB  - Fifty-one patients with established pulmonary tuberculosis underwent clinical
      evaluation and endoscopic examination of the larynx to determine the
      manifestations of laryngeal involvement. There were 46 males and 5 females (mean
      age 38 years). Fever, cough and haemoptysis were the prime pulmonary complaints
      while hoarseness, weak voice and episodic dyspnoea were the main laryngeal
      symptoms. Sites of laryngeal lesions included true vocal cords, arytenoids and
      false vocal cords. Oedema, pallor, ulcers, vocal cord immobility and thickening
      were the main laryngeal lesions observed. Twenty-four (47%) cases showed
      morphological changes in the larynx. The presentation pattern was consistent with
      the classical description and predilection for laryngeal involvement was not
      demonstrated.

PMID- 9000829
TI  - Experience with larangeal mask airway in Pakistani patients.
AB  - One hundred and thirty seven adult patients undergoing peripheral surgery were
      studied regarding ease of larangeal mask airway (LMA) insertion, airway
      maintenance during surgery and complication encountered during insertion,
      maintenance and in the postoperative period. In a majority (84%) of patients, the
      airway was positioned correctly at the first attempt, 3% patients had mild
      laryngospasm at insertion and in 85% a good airway was obtained. No airway
      related problems were encountered intraoperatively. Two percent patients had
      laryngospasm on removal of LMA. Postoperatively, the complaint of sore throat and
      uvular trauma was seen in 4% cases.

PMID- 9000830
TI  - Incidence of postdural puncture headache following spinal anaesthesia for lower
      segment caesarean section with the 25 gauge polymedic spinal needle.
AB  - The incidence of postdural puncture headache (PDPH) was studied in in-patients
      after spinal anaesthesia with 25 gauge Polymedic needle (Sprotte-like), for lower
      segment caesarean section (LSCS). A total of 281 women who underwent LSCS were
      studied, at the maternity unit of St. Peter's Hospital, Chertsey, Surrey, U.K. Of
      these, 125 women had a spinal, 93 general and 63 epidural anaesthesia. All the
      women were questioned about the presence of headache between the second and
      fourth post-operative day. Its severity was assessed with a visual analogue
      scale. Women who had an epidural or a general anaesthesia were used as controls.
      Out of 281 women studied, none complained of PDPH. Four women in the spinal
      anaesthetic group, complained of headache which did not have the characteristics
      of PDPH. The 25 gauge Polymedic spinal needle appears to be safe and satisfactory
      for performing spinal anaesthesia for LSCS.

PMID- 9000831
TI  - Simple intratesticular cyst: a case report.

PMID- 9000832
TI  - Epidermodysplasia verruciformis.

PMID- 9000833
TI  - Teenagers' smoking--a great public health problem, renewing the pool of smokers.

PMID- 9000836
TI  - The Warsaw Poison Control Centre, member of the World Network.

PMID- 9000835
TI  - Clinical pharmacology in the 1990s: a personal perspective.

PMID- 9000837
TI  - Comparative pharmacokinetics and bioavailability of flavonoid glycosides of
      Ginkgo biloba after a single oral administration of three formulations to healthy
      volunteers.
AB  - Eighteen healthy volunteers received three different formulations of Ginkgo
      biloba: capsules (A) and drops (B) (delivered by Agon Pharma), and tablets (C)
      (Tebonin-Dr. W. Schwabe) in equal an quantity, orally as a single dose, at an
      interval of at least five days. The pharmacokinetic parameters of the most
      important flavonoid glycosides: quercetin, kaempferol and isorhamnetin were
      established. The bioavailability was estimated using capsules as a standard
      formulation. Only the time to reach the peak concentration (tmax) of quercetin,
      kaempforol and isorhamnetin administered in the form of capsules, was
      significantly prolonged as compared with drops and tablets. Area under the curve
      (AUC) was the largest for formulation B for all the evaluated flavonoid
      glycosides, however the differences were not statistically significant. It is
      concluded that the three formulations of Ginkgo biloba extract are bioequivalent.

PMID- 9000839
TI  - A comparative study of: long-term alpha-1-blocker, Doxazosin therapy versus
      surgery in the treatment of benign prostatic hyperplasia.
AB  - Results of surgically treated BPH patients 6 mo. after surgery (Group I) were
      compared with those obtained in patients treated with Doxazosin for 3 yrs. (Group
      II). Surgery provided better improvement in uroflowmetry parameters, residual
      volume values and obstructive symptom scores (complete relief). Nevertheless,
      urinary flow rates normalized upon Doxazosin therapy. Higher prostate specific
      antigen (PSA) levels in Group II may be explained by the greater size of the
      adenoma. Postoperative adverse events were reported by some patients in contrast
      with those treated with Doxazosin. Doxazosin, due to its symptomatic and
      uroflowmetric efficacy, favourable safety profile and simple dosing schedule has
      a place in the management of symptomatic BPH patients.

PMID- 9000838
TI  - The acetylation and oxidation phenotypes in insulin-dependent diabetes mellitus.
AB  - Polymorphism of the acetylation and oxidation phenotypes in patients with IDDM
      was evaluated. A greater statistically significant number of fast acetylators in
      IDDM was found.

PMID- 9000840
TI  - A questionnaire for the assessment of quality of life in cancer patients in
      Turkey.
AB  - In this study, we developed a reliable scale to measure the quality of life
      (QOL), which would reflect the cultural characteristics of cancer patients in
      Turkey. We used the Rolls-Royce model and determined a form with 49 items in
      eight dimensions such as general well-being, physical symptoms and activity,
      sleep dysfunctions, appetite, sexual dysfunction, cognitive functions, medical
      interaction, social participation and work performance. The forms were used for
      assembling data from 100 subjects (10 physicians, 19 healthy volunteers, 18
      patients relatives, 28 patients on chemotherapy, 25 patients off chemotherapy).
      Half-split reliability and the signal effect were used to demonstrate reliability
      and responsiveness. After demonstrating the validity of the test, the final form
      was constructed. When these eight dimensions were factor analysed, it was found
      that the general well-being and sexual dysfunction were the most important
      determinants of QOL.

PMID- 9000841
TI  - Synthesis of novel, aminoalkanolic derivatives of 5,7-dihydroxy-2
      phenylbenzopyran-4-on as the potential cytostatic agents.
AB  - The 7-(2,3-epoxypropoxy)-2-phenyl-5-hydroxy-4H-benzopyran-4-on and its
      aminoalkanolic derivatives were prepared as the potential cytostatic
      (antileukemic) compounds. They were tested in vivo on mice leukemia L1210.

PMID- 9000843
TI  - The issue of privacy.

PMID- 9000842
TI  - Evaluating commercial computing systems.

PMID- 9000845
TI  - Clinical informatics: a new paradigm. First Consulting Group.

PMID- 9000844
TI  - Support groups in cyberspace.

PMID- 9000846
TI  - Using automated continual performance assessment to improve health care.
AB  - Inefficiency in the work of health care providers is evident and contributes to
      health care costs. In the early 20th century, industrial engineers developed
      scientific methods for studying work to improve performance (efficiency) by
      measuring results--i.e., quality, cost, and productivity. In the mid-20th
      century, business managers developed ways to apply these methods to improve the
      work process. These scientific methods and management approaches can be applied
      to improving medical work. Fee-for-service practice has had incentives to
      maximize productivity, and prepaid practice has had incentives to minimize costs,
      but no sector of the health care system has systematically pursued the
      optimization of all performance variables: quality, cost, and productivity. We
      have reviewed evolving methods for the automation of continual assessment of
      performance in health care using touch screen and computer telephone, logging and
      scheduling software, appropriate combinations of generic or disease-specific
      health status questionnaires, physiologic measurements or laboratory assays from
      computerized records, and cost and productivity data from computerized
      registration logs. We propose that the results of outcome assessment be rapidly
      and continually transmitted to providers, patients, and managers so that health
      care processes can be progressively improved. The evolving systems we have
      described are the practical tools that can help us achieve our performance goals.

PMID- 9000847
TI  - Using Java to design an automated patient record for the Web.

PMID- 9000848
TI  - Implementation of a comprehensive computer-based patient record system in Kaiser
      Permanente's Northwest Region.
AB  - Kaiser Permanente, Northwest Region, has implemented a comprehensive outpatient
      computer-based patient record. Clinicians use this system to document encounters,
      code diagnoses and procedures, maintain problem lists, order laboratory and
      radiology tests, and send prescriptions electronically. Clinicians also use it to
      send patient-specific messages and referrals between medical providers. More than
      300 primary care clinicians in 10 separate clinics are now using the system in
      the delivery of care. This article describes our strategy and experience in the
      implementation of a comprehensive computer-based patient record.

PMID- 9000849
TI  - The sixth level of electronic health records: a look beyond the screen.
AB  - A recent publication details five levels of electronic health records as defined
      by the Medical Records Institute and notes that no computer-based patient record
      system from any company meets the criteria set by the Institute of Medicine. The
      present article calls to the attention of potential purchasers of medical record
      software our observation that even if a package appears to meet the abstract
      criteria for all five levels of electronic health records, its performance may
      not be satisfactory. A look beyond the user interface screen is highly
      recommended. Examples from our recent experience are given.

PMID- 9000850
TI  - Outcome analysis: considerations for an electronic health record.
AB  - The concept of analyzing large observational databases, including fully
      electronic health records, to determine optimal patterns of care and ideal
      treatment strategies has blossomed now that large organizations and government
      agencies are recognizing the potential value of computer-stored patient
      information. However, computer-based patient records may not offer the detail and
      uniformity in presentation of clinical data that are needed for accurate analysis
      of their contents. In addition, pooling data from multiple electronic sources to
      perform outcome studies is impeded by the absence of widely used standards for
      data interchange and data representation. This report examines the requirements
      for outcome analysis and the features that a computerized clinical database
      should possess in order to minimize data ambiguity and ensure that the results of
      outcome-studies are meaningful.

PMID- 9000851
TI  - An automated nursing assessment for a teaching hospital.
AB  - An automated nursing assessment has been developed by the Department of Nursing
      and the Center for Clinical Computing at Beth Israel Hospital and Harvard Medical
      School. Designed to collect standardized data using structured and free-text
      entry of patient-specific data, the program has been in use on all medical and
      surgical inpatient units since July 1994. Before it was implemented, each nursing
      unit had used its own format to document the nursing assessment and there was no
      standardization of information. The automated system has decreased repetitive
      entry of data items, improved the legibility and availability of baseline
      information, increased patient-related communication between nursing units, and
      reduced the average time spent documenting the admission assessment from 60 to 30
      minutes.

PMID- 9000852
TI  - [Severe congenital thoracic-lumbar scoliosis in pregnancy. A case report and
      review of the literature].
AB  - The authors describe a case report of a patient affected by congenital thoraco
      lumbar scoliosis of a severe degree, aged 32, para 0, gravida 1. She was
      submitted to orthopedic surgery in childhood. Cesarean section was performed at
      the 37th week of amenorrhoea. Pregnancy in severe defects of the spine, though
      becoming more and more uncommon, can still be encountered. Severe congenital
      scoliosis is a clinical problem; it affects not only the size and shape of the
      pelvis, but also sometimes results in significant maternal cardiovascular and
      respiratory complication. The authors, reviewing the literature, evaluate the
      anatomical and functional (from a biomechanical point of view) derangement of the
      pelvis, the problem of vaginal delivery and the clinical and radiological
      assessment of the problem, especially evaluating the cardio-pulmonary function.
      In conclusion, pregnancy in patients with severe scoliosis can be managed
      successfully by close monitoring especially of the respiratory function. The
      decision of the route of delivery is related to clinical assessment and obstetric
      indications.

PMID- 9000853
TI  - Needs assessment in general practice.

PMID- 9000855
TI  - Avoiding medication mixups. Identifiable imprint codes.
AB  - This study was done to determine if current imprinting of solid medication forms
      permits health care professionals to identify the manufacturers involved so as to
      be able to activate the hierarchic identification system mandated by the Food and
      Drug Administration. We tested 15 representatives of 6 groups of health
      professionals for their ability to identify the manufacturer after having
      examined 30 solid-dosage forms drawn from a pseudo-random sample of stock
      hospital formulary products. The correct identification of the manufacturer was
      the sole criterion. Of the 2,700 opportunities, the manufacturer was able to be
      identified for only 43%. Nurses and medical students had a 35% success rate,
      pharmacists and poison center specialists a 55% success rate, and residents and
      attending physicians a 40% rate. None approached 95% accuracy. Currently employed
      imprints fail in their objective to permit health care professionals--or the
      general public--to rapidly identify prescription drugs. The manufacturers'
      logotypes need to be modified if this identification system is to be implemented.
      We propose a simple voluntary collaborative effort by the pharmaceutical industry
      to solve the problem.

PMID- 9000854
TI  - Onychomycosis. New therapies for an old disease.
AB  - The newer generation of antifungal agents such as itraconazole and terbinafine
      are more effective than the older therapies, griseofulvin and ketoconazole, in
      the treatment of dermatophyte pedal onychomycosis. Itraconazole can be
      administered as continuous dosing, 200 mg per day for 3 months, or in the form of
      pulse therapy, 200 mg twice a day for 1 week per month for 3 consecutive months.
      Terbinafine is given as continuous dosing, 250 mg per day for 3 months.

PMID- 9000856
TI  - Lung transplantation. Part I. Indications and operative management.
AB  - In the past 8 years, lung transplantation has become a standard therapy for
      benign end-stage pulmonary disease. Rapid advances have occurred involving
      indications and operative management that have allowed pulmonary transplantation
      to be a viable option for an increasingly diverse patient population. In part I,
      we review the current indications and operative techniques, and in part II we
      will cover the postoperative management and results.

PMID- 9000858
TI  - Prematurity--steroids for all.

PMID- 9000859
TI  - Intracytoplasmic sperm injection.

PMID- 9000857
TI  - Myocardial viability.
AB  - Left ventricular function is a major predictor of outcome in patients with
      coronary artery disease. Acute ischemia, postischemic dysfunction (stunning),
      myocardial hibernation, or a combination of these 3 are among the reversible
      forms of myocardial dysfunction. In myocardial stunning, dysfunction occurs
      despite normal myocardial perfusion, and function recovers spontaneously over
      time. In acute ischemia and hibernation, there is regional hypoperfusion.
      Function improves only after revascularization. Evidence of myocardial viability
      usually relies on the demonstration of uptake of various metabolic tracers, such
      as thallium (thallous chloride TI 201) or fludeoxyglucose F 18, by dysfunctional
      myocardium or by the demonstration of contractile reserve in a dysfunctional
      region. This can be shown as an augmentation of function during the infusion of
      various sympathomimetic agents. The response of ventricular segments to
      increasing doses of dobutamine may indicate the underlying mechanism of
      dysfunction. Stunned segments that have normal perfusion show dose-dependent
      augmentation of function. If perfusion is reduced as in hibernating myocardium,
      however, a biphasic response usually occurs: function improves at low doses of
      dobutamine, whereas higher doses may induce ischemia and, hence, dysfunction. But
      in patients with severely impaired perfusion, even low doses may cause ischemia.
      Myocardial regions with subendocardial infarction or diffuse scarring may also
      have augmented contractility during catecholamine infusion due to stimulation of
      the subepicardial layers. In these cases, augmentation of function after
      revascularization is not expected. Because the underlying mechanism, prognosis,
      and therapy may differ among these conditions, it is crucial to differentiate
      among dysfunctional myocardial segments that are nonviable and have no potential
      to regain function, hibernating or ischemic segments in which recovery of
      function occurs only after revascularization, and myocardial stunning in which
      function is expected to recover spontaneously. Because combinations of all of
      these disorders may occur, even in the same segments, caution should be used in
      interpreting the imaging results.

PMID- 9000860
TI  - Androgen replacement in postmenopausal women.

PMID- 9000862
TI  - Managing viral exposure during pregnancy.

PMID- 9000861
TI  - Adolescent contraception.

PMID- 9000863
TI  - Assisted reproductive technologies.

PMID- 9000864
TI  - Ruptured sinus of Valsalva aneurysm in a patient with autosomal dominant
      polycystic kidney disease.

PMID- 9000865
TI  - Diabetic neuropathic cachexia.

PMID- 9000866
TI  - Approach to patients with hirsutism.
AB  - Hirsutism is a common medical condition that in most women is due to the
      polycystic ovary syndrome or is idiopathic. For a few women, hirsutism signals a
      serious underlying disorder such as an ovarian or adrenal tumor, congenital
      adrenal hyperplasia, or Cushing's syndrome. A detailed medical history and
      examination can identify women in whom a serious disease is suspected and for
      whom laboratory evaluation is warranted. Measurements of serum testosterone,
      dehydroepiandrosterone, and 17 alpha-hydroxyprogesterone levels, and 24-hour
      urinary cortisol concentrations are important screening tests. Therapy is
      directed at suppressing ovarian or adrenal androgen production, inhibiting the
      conversion of testosterone to dihydrotestosterone, or antagonizing the effects of
      androgens at the receptor level.

PMID- 9000867
TI  - What we see most, we understand least.

PMID- 9000868
TI  - The search for viable myocardium.

PMID- 9000869
TI  - Violence in America.

PMID- 9000870
TI  - Do premedical students fear being sued?

PMID- 9000871
TI  - Differentiation between dyspnea and its affective components.
AB  - This study investigated whether people with chronic obstructive pulmonary disease
      (COPD) can differentiate distress and anxiety associated with dyspnea from the
      intensity of dyspnea and the perceived effort of breathing. Fifty-two subjects
      with COPD rated their perception of the individual components of dyspnea on a 200
      mm visual analog scale at rest, after a 6-min walk (6MD), and every 2 min during
      an incremental treadmill test (ET). Subjects differentiated among the four
      dyspnea components at the end of the 6MD (p < .0001) and during ET (at rest, p <
      0.001; at 75% VO2 max, p < 0.0001; and at end exercise, p < 0.0001). Intensity
      was significantly related to perceived effort of breathing (p < .0001), as
      distress was to anxiety (p < .0001), suggesting that each pair measures similar
      components. Subjects were able to differentiate their affective response to
      dyspnea from the intensity of the symptom. Measurement of a patient's affective
      response to dyspnea may improve the selection of specific treatments and validity
      of outcomes.

PMID- 9000872
TI  - Self-reported food reactions and their associations with asthma.
AB  - The role of food reactions in asthma has not been well described. The objectives
      of this study were to evaluate the types of self-reported reactions to foods in
      asthmatic patients, and to determine the association between self-reported food
      reactions and self-reported severity of asthma and asthma health care
      utilization. We characterized 914 patients, aged 3-55 years, in a large health
      maintenance organization. We characterized the patients according to demographic
      data (age, sex, occupation, SES, marital status) and their asthma according to
      duration, triggers, severity (symptoms, FEV1 percentage predicted) and presence
      of atopy. Overall, 414 (45.3%) participants, primarily women, reported adverse
      reactions to food, particularly milk, red wine, eggs, chocolate, and peanuts.
      Those with food reactions were more likely to report having ever been
      hospitalized for breathing problems than those without food reactions (31% vs.
      22%, two-tailed p = 0.004) although their asthma was not worse. Self-reported
      food reactions, particularly in females, may be associated with increased asthma
      health care utilization, and such patients may require closer health care
      management.

PMID- 9000873
TI  - Family stress and support among former Soviet immigrants.
AB  - The purpose of this qualitative descriptive study was to investigate types of
      family support and stress among former Soviet immigrants. Forty-two immigrants
      (14 males and 28 females) were interviewed about their immigration experiences,
      including description of current relationships with family in the resettlement
      country. Content analysis of interview data documented that immigrant families
      can be a valuable source of emotional and/or instrumental support. Immigrant
      families, however, can also be too overwhelmed by their own immigration demands
      to provide support or can generate additional stress for its members. Types of
      family stress included conflict from differing values and opinions, increased
      responsibility for family members who could not manage resettlement on their own,
      family members' emotional distress over immigration experiences, unmet
      expectations for family members' adjustment, and changes in household composition
      and living arrangements upon arrival in the United States.

PMID- 9000874
TI  - Older couples' decision making on health issues.
AB  - The purpose of this qualitative study was to determine the process of spousal
      influence as it relates to health-promotion behaviors and the concept desire to
      change spousal health behaviors. Fifty-nine elderly couples in long-term
      marriages were recruited through three senior centers; participants were asked to
      respond to five open-ended questions. The majority of couples said that they made
      health decisions jointly; wives tended to be the primary deciders in the even
      that a health decision had to be made. Most people, but particularly wives,
      desired to change something about their spouses' health behavior; a variety of
      strategies were used in the attempt to change spousal behavior. Aging or illness
      in the self or spouse were identified as precipitants of increased desire to
      change the spouses' health behavior over time.

PMID- 9000875
TI  - Critical care nurses' lived experience of unsuccessful resuscitation.
AB  - Although approximately 58% of patients in critical care units die despite
      resuscitation efforts, the experience of nurses who participate in unsuccessful
      patient resuscitation has been largely unexamined. The article is a description
      of a phenomenological research study designed to investigate this experience.
      Nine nurses employed in cardiac or intensive care units of a tertiary care
      hospital participated in the study by contributing paradigm narratives concerning
      unsuccessful patient resuscitation. The lived experience of unsuccessful
      resuscitation was described by the participants as one in which they fortified
      themselves for the emotional consequences and sense of loss associated with this
      experience while establishing a connectedness with the patient and his/her
      significant others.

PMID- 9000876
TI  - Response to editorial "Overcoming national and cultural differences within
      collaborative international nursing research".

PMID- 9000877
TI  - Response to "Assuring quality in narrative analysis".

PMID- 9000878
TI  - Protective effect of Oenanthe javanica on the hepatic lipid peroxidation in
      bromobenzene-treated rats and its bioactive component.
AB  - To investigate the detoxification of bromobenzene-induced hepatic lipid
      peroxidation by Oenanthe javanica DC, the hepatic lipid peroxide level and the
      activities of enzymes responsible for production and removal of epoxide were
      studied. The level of lipid peroxide elevated by bromobenzene was significantly
      reduced by the methanol extract (250 mg/kg) and persicarin (5 mg/kg). The
      methanol extract and persicarin administered daily over 4 weeks before
      intoxication with bromobenzene did not affect the activities of aminopyrine N
      demethylase, aniline hydroxylase, and glutathione S-transferase. Epoxide
      hydrolase activity was decreased significantly by bromobenzene, which was
      restored to the control level by pretreatment with persicarin. However, the
      identical pretreatment with isorhamnetin and hyperoside did not change the enzyme
      activity or lipid peroxide level. The results suggest that the reduction of
      bromobenzene-induced hepatic lipid peroxidation by O. javanica under our
      experimental conditions is effected through enhancing the activity of epoxide
      hydrolase, an enzyme removing bromobenzene epoxide. In addition, the bioactive
      component of this plant responsible for the detoxification of bromobenzene, at
      least in part, is thought to be persicarin.

PMID- 9000879
TI  - Benzophenanthridine alkaloids of Chelidonium majus; II. Potent inhibitory action
      against the growth of human keratinocytes.
AB  - The benzophenanthridine alkaloids sanguinarine and chelerythrine of Chelidonium
      majus, L. (Papaveraceae), were tested for their action against the growth of
      human keratinocytes. Cell proliferation was independently determined by directly
      counting the cells and in the colorimetric MTT assay. Sanguinarine potently
      inhibited cell growth with an IC50 of 0.2 microM. Chelidonine, the main alkaloid
      of Ch. majus, was much less efficient. The extract of the herb of Ch. majus was
      also effective with an IC50 of 1.9 microM, calculated on the basis of its
      alkaloid content in terms of chelidonine. Keratinocytes were further tested for
      their susceptibility for the action of sanguinarine and chelerythrine on plasma
      membrane integrity, which resulted in a twofold increase in lactate dehydrogenase
      (LDH) activity as compared to controls. On the other hand, the activity of the
      extract of the herb of Ch. majus was due to cytostatic rather than cytotoxic
      effects, as LDH release was unchanged as compared to controls.

PMID- 9000880
TI  - Procyanidines from Vitis vinifera seeds protect rabbit heart from
      ischemia/reperfusion injury: antioxidant intervention and/or iron and copper
      sequestering ability.
AB  - An isolated rabbit heart Langendorff preparation paced electrically was used to
      evaluate the effects of a highly purified, high molecular weight fraction of
      oligomeric procyanidines isolated from Vitis vinifera seeds on myocardial
      reperfusion injury after 40 minutes of low flow (1 ml/min) ischemia. Infusion of
      the heart with 100 or 200 micrograms/ml procyanidines dose-dependently reduced
      ventricular contracture during ischemia (LVEDP values decreased by 28% and 51%),
      decreased coronary perfusion pressure (CPP), improved cardiac mechanical
      performance upon reperfusion, increased the release of 6-keto-PGF1 alpha into the
      perfusate in both the pre-ischemic and the reperfusion periods (by 68% at 200
      micrograms/ml), and suppressed rhythm irregularity. This antiarrhythmogenic
      action was confirmed in a more severe model of ischemia (flow rate 0.2 ml/ min).
      The cardioprotective agent allopurinol infused at 20 micrograms/ml had effects on
      the contractility and on the release of 6-keto-PGF1 alpha comparable to those of
      200 micrograms/ml procyanidines. The results of the second part of this study
      show that procyanidines are potent scavengers of several reactive oxygen species
      involved in the ischemia/reperfusion damage: the superoxide anion (IC50 = 5.64
      microM: rate constant K = 7.55 x 10(5) M-1 s-1, determined by the phenazine
      methosulfate/NADH method); the hydroxyl radical (IC50 = 28 microM; rate constant
      K = 1.2 x 10(12) M-1 s-1, determined by the electron spin resonance
      spectroscopy); peroxyl radicals (IC50 = 0.025 microM and 0.35 microM, determined
      using two different lipid substrates, phosphatidylcholine liposomes and methyl
      linoleate micelles by UV spectroscopy at 233 nm). Finally, procyanidines interact
      with Fe2+ and Cu2+ ions (the catalysts of HO. radicals production) giving rise to
      strong complexes, with stability constants (log K) ranging from 9.35 to
      approximately 9.

PMID- 9000881
TI  - Myocardial protective effect of honokiol: an active component in Magnolia
      officinalis.
AB  - Honokiol is an active component of Magnolia officinalis. It was reported to be
      1000 times more potent than alpha-tocopherol in inhibiting lipid peroxidation in
      rat heart mitochondria. In this study, we investigated the in vivo antiarrhythmic
      and antiischemic effects of honokiol in coronary ligated rats. Male Sprague
      Dawley rats were anesthetized with urethane. Honokiol, at dosages of 10(-7) g/kg,
      10(-8) g/kg, and 10(-9) g/kg, was administered intravenously 15 min before
      ligation of the coronary artery. Incidence and duration of ventricular
      tachycardia and ventricular fibrillation during 30 min coronary ligation were
      significantly reduced by 10(-7) g/kg honokiol. Ventricular arrhythmia during 10
      min reperfusion after the relief of coronary ligation was also reduced. In rats
      subjected to 4 hours coronary ligation, 10(-7) g/kg, 10(-8) g/kg, and 10(-9) g/kg
      honokiol significantly reduced the infarct zone. We concluded that honokiol may
      protect the myocardium against ischemic injury and suppress ventricular
      arrhythmia during ischemia and reperfusion.

PMID- 9000882
TI  - Spasmolytic activity of a lipidic extract from Sabal serrulata fruits: further
      study of the mechanisms underlying this activity.
AB  - The mechanisms involved in the spasmolytic effect of a lipidic extract from Sabal
      serrulata fruits were investigated. The extract relaxed vanadate-induced
      contractions on rat uterus incubated in a calcium free solution (EC50 = 11.41 +/-
      1.38 micrograms/ml). The modification of the effect by a cyclooxygenase inhibitor
      (indomethacin), a protein kinase A inhibitor (TPCK), calcium modifying drugs, and
      drugs interfering with transcription and protein synthesis has been assayed. The
      effect was unmodified by a 3 microM concentration of indomethacin, (EC50 = 8.77
      +/- 1.28 vs 11.41 +/- 1.38 micrograms/ml) and a 5 micrograms/ml concentration of
      the transcription inhibitor, actinomycin D, (EC50 = 8.23 +/- 2.19 vs 11.41 +/-
      1.38 micrograms/ml). The inhibitor of intracellular calcium mobilization TMB-8
      (0.1 mM), the Na+/Ca+2 exchanger inhibitor amiloride (0.1 mM), the calcium
      chelator BAPTA-AM (50 microM), the PKA inhibitor TPCK (10 microM), and the
      protein synthesis inhibitor cycloheximide (10 micrograms/ml) significantly
      shifted to the right the dose-response curve of the extract (EC50 = 17.83 +/-
      1.87 micrograms/ml, 18.61 +/- 2.50 micrograms/ml, 35.28 +/- 9.13 micrograms/ml,
      33.99 +/- 3.07 micrograms/ml, and 27.31 +/- 4.93 micrograms/ml, respectively, vs
      11.41 +/- 1.38 micrograms/ml). These results suggest that the effect of the
      lipidic extract from S. serrulata fruits could be partially due to Na+/Ca+2
      exchanger activation and interference with intracellular calcium mobilization,
      and point to cAMP as a possible mediator. Moreover, protein synthesis seems to be
      involved in the spasmolytic activity.

PMID- 9000883
TI  - Tonkinelin: a novel annonaceous acetogenin from Uvaria tonkinensis.
AB  - Further studies on the root bark of Uvaria tonkinensis Finet et Gagnep.
      (Annonacease) led to the isolation of a new Annonaceous acetogenin, tonkinelin
      (1). The structure of 1 was elucidated on the basis of spectral data and chemical
      evidence. This compound represents an unusual type of C37 Annonaceous acetogenin,
      having neither tetrahydrofuran (THF) nor epoxide rings and possessing only a
      vicinal diol in the hydrocarbon chain. Preliminary pharmacological tests showed
      that tonkinelin (1) inhibits human leukemia (HL-60) and human colon
      adenocarcinoma (HCT-8) cell lines in vitro.

PMID- 9000884
TI  - A new triterpenoid saponin, bredemeyeroside B. from the roots of Bredemeyera
      floribunda.
AB  - A new triterpenoid saponin named bredemeyeroside B has been isolated from the
      roots of Bredemeyera floribunda and its structure elucidated as 3-O-beta-D
      glucopyranosyl-2 beta, 3 beta, 27-trihydroxyolean-12-en-23,28-dioic acid 28-O
      beta-D-xylopyranosyl-(1-->4)-[beta-D-apiofuranosyl-(1-->3)]-a lpha -L
      rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->3] -beta-D-fucopyranoside
      by means of MS, NMR and chemical evidence. In addition rutin was also isolated.
      In laboratory tests bredemeyeroside B showed snake venom antidote activity.

PMID- 9000885
TI  - New dimeric aporphine alkaloids and cytotoxic constituents of Hernandia
      nymphaeifolia.
AB  - Three minor new dimeric aporphine alkaloids, oviisocorydine (1), ovihernangerine
      (2), and oxohernandaline (3), along with four known alkaloids, (+)-hernandaline,
      (+)-thallcarpine, (+)-N-methylovigerine, and N-methylcorydaldine, and five known
      lignans, (+)-epimagnolin, (+)-epiaschantin, (+)-epiyangambin, (-)
      deoxypodophyllotoxin, and (-)-yatein, have been additionally isolated from the
      trunk bark of Hernandia nymphaeifolia. The structures of these compounds were
      elucidated by spectroscopic methods. Among forty-four isolates obtained till now,
      nine compounds, hernandonine (4), hernanymphine (5), demethylsonodione (6), (+)
      ovigerine (7), (+)-N-methylovigerine (8), N-formyldehydroovigerine (9), 4
      methoxyoxohernandaline (10), (-)-deoxypodophyllotoxin (11), and (-)-yatein (12)
      showed significant cytotoxic activities (ED50 values < 1 microgram/ml) against P
      388, KB16, A549, and HT-29 cell lines.

PMID- 9000887
TI  - Gas chromatographic/mass spectrometric detection of narcotine, papaverine, and
      thebaine in seeds of Papaver somniferum.
AB  - In addition to codeine and morphine, three more compounds: narcotine (noscapine),
      papaverine, and thebaine were found in Indian and Netherlands poppy seeds
      (Papaver somniferum L). The compounds were detected by a GC/MS technique and the
      identities were confirmed by comparing retention times and ion ratios with the
      known references. The concentrations of codeine, morphine, thebaine, papaverine,
      and narcotine were 44, 167, 41, 67, and 230 micrograms/g in Indian poppy seeds,
      and were 1.8, 39, 1.0, 0.17, 0.84 micrograms/g in Netherlands poppy seeds,
      respectively. Because these compounds may be urinary products after poppy seed
      consumption, the lowest detectable concentrations of codeine, morphine, thebaine,
      papaverine, and narcotine in urine are of interest and were found to be 4, 4, 5,
      0.4, and 4 ng/ml, respectively. The detection of urinary narcotine, papaverine,
      or thebaine may be utilized to differentiate poppy seed consumption from illicit
      codeine, morphine, or heroin use.

PMID- 9000886
TI  - Constituents of Veltheimia viridifolia; I. Homoisoflavanones of the bulbs.
AB  - The new homoisoflavanone R(-)-3-(4-hydroxybenzyl)-5-hydroxy-6, 7,8
      trimethoxychroman-4-one (1) was isolated from the petroleum ether and the diethyl
      ether extracts of the bulbs of Veltheimia viridifolia (Hyacinthaceae) together
      with the known homoisoflavanone muscomin (2). The structures of the compounds
      were elucidated by means of 1H-NMR, 2D 1H-1H-COSY, 13C-NMR, HMQC, HMBC, mass, and
      CD spectra. Pharmacological testings of the new homoisoflavanone are reported.

PMID- 9000888
TI  - Polymethoxylated xanthones from the herb of Centaurium erythraea with strong
      antimutagenic properties in Salmonella typhimurium.
AB  - Two methoxylated xanthone derivatives, eustomin and demethyleustomin, were
      isolated from the aerial parts of Centaurium erythraea Rafn. Both compounds were
      identified by spectral analysis. They showed strong antimutagenic properties in
      Salmonella typhimurium strains TA98, TA100, and TA102, when tested against 2
      nitrofluorene, 2-aminoanthracene, ethyl methanesulfonate, and nalidixic acid. The
      bioantimutagenic character of the compounds was supported by the strong effects
      shown in post-treatment experiments as well as by results obtained with rec A-
      mutants of E. coli and Bacillus subtilis. From this it follows that the xanthone
      derivatives probably interfere mainly with the process of post-replication
      repair.

PMID- 9000889
TI  - Antineoplastic agents; I. Three spirostanol glycosides from rhizomes of Dioscorea
      collettii var. hypoglauca.
AB  - By activity-guided fractionation, three known steroidal saponins, prosapogenin A
      of dioscin, dioscin and gracillin, were isolated from the total saponin fraction
      of Dioscorea coiletti var. hypoglauca as active compounds causing morphological
      abnormality of Pyricularia oryzae mycelia. The compounds also exhibited cytotoxic
      activity against the cancer cell line K562 in vitro. The structures of the
      compounds were elucidated on the basis of chemical evidence and IR, FAB-MS, 1H
      NMR, 13C-NMR, and two-dimensional NMR (2D-NMR) analysis.

PMID- 9000890
TI  - Shaping perceptions to motivate healthy behavior: the role of message framing.
AB  - Health-relevant communications can be framed in terms of the benefits (gains) or
      costs (losses) associated with a particular behavior, and the framing of such
      persuasive messages influences health decision making. Although to ask people to
      consider a health issue in terms of associated costs is considered an effective
      way to motivate behavior, empirical findings are inconsistent. In evaluating the
      effectiveness of framed health messages, investigators must appreciate the
      context in which health-related decisions are made. The influence of framed
      information on decision making is contingent on people, first, internalizing the
      advocated frame and, then, on the degree to which performing a health behavior is
      perceived as risky. The relative effectiveness of gain-framed or loss-framed
      appeals depends, in part, on whether a behavior serves an illness-detecting or a
      health-affirming function. Finally, the authors discuss the cognitive and
      affective processes that may mediate the influence of framed information on
      judgment and behavior.

PMID- 9000891
TI  - The emerging conceptualization of groups as information processors.
AB  - A selective review of research highlights the emerging view of groups as
      information processors. In this review, the authors include research on
      processing objectives, attention, encoding, storage, retrieval, processing,
      response, feedback, and learning in small interacting task groups. The groups as
      information processors perspective underscores several characteristic dimensions
      of variability in group performance of cognitive tasks, namely, commonality
      uniqueness of information, convergence-diversity of ideas, accentuation
      attenuation of cognitive processes, and belongingness-distinctiveness of members.
      A combination of contributions framework provides an additional conceptualization
      of information processing in groups. The authors also address implications,
      caveats, and questions for future research and theory regarding groups as
      information processors.

PMID- 9000892
TI  - Behavioral inhibition, sustained attention, and executive functions: constructing
      a unifying theory of ADHD.
AB  - Attention deficit hyperactivity disorder (ADHD) comprises a deficit in behavioral
      inhibition. A theoretical model is constructed that links inhibition to 4
      executive neuropsychological functions that appear to depend on it for their
      effective execution: (a) working memory, (b) self-regulation of affect-motivation
      arousal, (c) internalization of speech, and (d) reconstitution (behavioral
      analysis and synthesis). Extended to ADHD, the model predicts that ADHD should be
      associated with secondary impairments in these 4 executive abilities and the
      motor control they afford. The author reviews evidence for each of these domains
      of functioning and finds it to be strongest for deficits in behavioral
      inhibition, working memory, regulation of motivation, and motor control in those
      with ADHD. Although the model is promising as a potential theory of self-control
      and ADHD, far more research is required to evaluate its merits and the many
      predictions it makes about ADHD.

PMID- 9000893
TI  - Developmental and social influences on young girls' early problem behavior.
AB  - A developing body of research suggests that there are few sex differences in the
      rate and severity of problem behavior in early childhood, but clear sex
      differences emerge at about 4 years of age. The authors explore 2 hypotheses to
      further the understanding of emerging sex differences in problem behavior across
      the first 5 years of life. The first posits that the change in girls' problem
      behavior from infancy to school entry represents a channeling of early problem
      behavior into predominantly internalizing problems as a result of socialization.
      The second hypothesis is that the change in girls' early problem behavior during
      the preschool period results from the more rapid biological, cognitive, and
      social-emotional development of girls relative to boys. The authors review
      research on the influence of parents, teachers, and peers on girls' behavior from
      infancy to preschool regarding the first hypothesis, whereas they review studies
      of sex differences in developmental processes to test the second. They find
      moderate support for both hypotheses and present a comprehensive theory of girls'
      developmental psychopathology that integrates social and developmental
      influences.

PMID- 9000894
TI  - Social cognition in schizophrenia.
AB  - The study of social cognition in schizophrenia may augment the understanding of
      clinical and behavioral manifestations of the disorder. In this article, the
      authors describe social cognition and differentiate it from nonsocial cognition.
      They garner evidence to support the role of social cognition in schizophrenia:
      Nonsocial information-processing models are limited to explain social dysfunction
      in schizophrenia, measures of social cognition may contribute greater variance to
      social functioning than measures of nonsocial cognition, task performance on
      nonsocial-cognitive measures may not parallel performance on social-cognitive
      tasks, and symptomatology may be best understood within a social-cognitive
      framework. They describe the potential implications of a social-cognitive model
      of schizophrenia for the etiology and development of the disorder.

PMID- 9000895
TI  - Counterfactual thinking.
AB  - Counterfactuals are mental representations of alternatives to the past and
      produce consequences that are both beneficial and aversive to the individual.
      These apparently contradictory effects are integrated in a functionalist model of
      counterfactual thinking. The author reviews research in support of the assertions
      that (a) counterfactual thinking is activated automatically in response to
      negative affect, (b) the content of counterfactuals targets particularly likely
      causes of misfortune, (c) counterfactuals produce negative affective consequences
      through a contrast-effect mechanism and positive inferential consequences through
      a causal-inference mechanism, and (d) the net effect of counterfactual thinking
      is beneficial.

PMID- 9000897
TI  - The future of the NHS belongs to the patient.

PMID- 9000896
TI  - The future of the NHS.

PMID- 9000898
TI  - Learning the lessons.

PMID- 9000899
TI  - Stress busters.

PMID- 9000901
TI  - Rebuilding work.

PMID- 9000900
TI  - Taxing patients.

PMID- 9000902
TI  - Nurse prescribing's time has come.

PMID- 9000903
TI  - Failure of trust.

PMID- 9000904
TI  - From home to home. Interview by Lynn Walsh.

PMID- 9000905
TI  - Memories for a lifetime.

PMID- 9000906
TI  - Root or branch reform?

PMID- 9000907
TI  - Nursing research on the King's Fund database.
AB  - Health workers are being urged to base their care and services on research. There
      are many sources of research available including the King's Fund Nursing
      Development Network database. The database currently mentions 104 research
      projects reported by network members. They vary in subject and depth and this
      article presents a selection of short descriptions from the database.

PMID- 9000908
TI  - Observing and describing nursing interactions.
AB  - This article describes the development of a programme to collect qualitative data
      on components of nursing care behaviour to supplement quantitative methods. Using
      hand-held computer technology, data were collected in forensic and mainstream
      psychiatric care settings. The study was able to show positive improvements in
      direct care to patients and health outcomes as well as provide the qualifying
      data necessary to initiate and implement change on management, administrative and
      nursing care levels. The author recommends that such data be fed into quality
      initiatives to allow effective and efficient use to be made of increasingly
      scarce nursing resources.

PMID- 9000909
TI  - A study of the factors in hip replacement dislocation. Part 2.
AB  - Dislocation is a dramatic and distressing common complication following total hip
      replacement. The first article describing this study, published last week,
      considered some of the factors thought to predispose to dislocation. The authors
      emphasised the multifactorial nature of hip replacement dislocation and in this
      second article they examine the factors relating to acetabular position and
      orientation, and femoral component placement.

PMID- 9000910
TI  - Nurse practitioners in general practice: an expanding role.
AB  - At a time when the government is proposing to allow nurses to become equal
      partners with GPs and a consultative report commissioned by the NHSE found that
      nurse practitioners provide cheaper and better services for patients (NHSE 1996),
      this article describes the role of a nurse practitioner working in a GP
      fundholding practice in the UK. The author considers issues of autonomy and
      accountability surrounding the development of the role. Its relationship to the
      development of nursing and caring is examined in the light of some doctors' and
      nurses' scepticism and ambivalence. The benefits to patients are presented to
      highlight the value of a properly structured nurse practitioner role integrated
      into primary care provision.

PMID- 9000912
TI  - Student nurse accommodation shortage.

PMID- 9000911
TI  - Colostomies and their management.
AB  - This article describes the common types of colostomy and outlines the basic
      principles of management. It relates to UKCC professional development category:
      Care enhancement.

PMID- 9000913
TI  - Administration of drugs--are nurses breaking the law?

PMID- 9000914
TI  - Wish you were here?

PMID- 9000915
TI  - Frontline challenge.

PMID- 9000916
TI  - Mixed blessing.

PMID- 9000917
TI  - Fellow travellers.

PMID- 9000918
TI  - Making a comeback.

PMID- 9000919
TI  - Professional education. Interview by Daniel Allen.

PMID- 9000920
TI  - Through the looking glass.

PMID- 9000921
TI  - Time for change.

PMID- 9000922
TI  - X-ray update.

PMID- 9000923
TI  - Patient satisfaction survey in a special hospital.

PMID- 9000924
TI  - Chlamydia trachomatis: symptoms and consequences.
AB  - In the second of two articles on sexually transmitted diseases, the author
      discusses chlamydia trachomatis. The article reviews the symptoms and
      consequences of chlamydia infection, and recommends an education strategy to
      increase public and professional awareness of the condition.

PMID- 9000926
TI  - Peripheral blood stem cell transplantation. Part 1.
AB  - This is the first of a two-part article examining the increasing use of
      peripheral blood stem cell transplant as a treatment for certain types of
      malignancy. In this article the author reviews the history of the treatment and
      discusses how the cells are collected. The second article considers the nursing
      care of patients undergoing transplant and looks at the future implications of
      the treatment.

PMID- 9000925
TI  - Methods of wound assessment documentation: a study.
AB  - This study investigated whether relevant parameters of wound assessment are
      documented more frequently if a wound assessment chart is used. Wound assessment
      documents from three clinical areas were analysed. Content analysis was carried
      out on all of the wound assessment documents. Criteria against which to analyse
      the documents were formulated from a literature review. The hypothesis that
      relevant parameters of wound assessment were documented more frequently when a
      wound assessment chart was used was supported. Some criticisms and potential
      improvements of the wound assessment chart also emerged.

PMID- 9000927
TI  - Access and activism.

PMID- 9000928
TI  - Why did students fail?

PMID- 9000929
TI  - Easy targets.

PMID- 9000930
TI  - Nurse prescribing.

PMID- 9000931
TI  - Quality costs.

PMID- 9000932
TI  - Putting health centre stage.

PMID- 9000933
TI  - Shop till we drop.

PMID- 9000934
TI  - Bad days and sad days.

PMID- 9000935
TI  - Left holding the baby.

PMID- 9000936
TI  - Influencing the influential.

PMID- 9000937
TI  - Nurses await directive.

PMID- 9000938
TI  - On with the new.

PMID- 9000939
TI  - New government must mean new deal for nursing.

PMID- 9000940
TI  - Worldly Woman.

PMID- 9000942
TI  - Clinical review of 1996.

PMID- 9000941
TI  - Challenge ahead.

PMID- 9000943
TI  - The dynamics of rumours in the clinical setting.
AB  - In this article the social and psychological aspects of rumours are considered.
      The authors place rumours in a wider social context using definitions of
      different types of rumour before focusing on the nature of rumours in the
      healthcare environment. Some of the positive and negative consequences of rumours
      are examined and strategies which can help to minimise the spread of the
      misinformation characteristically contained in hospital rumours are highlighted.

PMID- 9000944
TI  - Witnessing violence to staff: a study of nurses' experiences.
AB  - This article highlights a study into the effects of witnessing violence in a
      psychiatric hospital setting. The results show that the majority of respondents
      who had witnessed violence to a colleague experienced similar emotional distress
      as the victims. The authors suggest measures that may help staff in these and
      other clinical areas. They conclude that violence to staff should not be an
      accepted part of the working environment.

PMID- 9000945
TI  - A validation approach to severely demented clients.

PMID- 9000946
TI  - Using aromatherapy in the management of psoriasis.
AB  - Psoriasis is an uncomfortable, inflammatory skin disease for which there is no
      cure but which can be managed at an acceptable level for the individual. This
      article explores the use of aromatherapy as an alternative management approach.
      The author describes a range of treatment outcomes, which show both physiological
      and psychological benefits.

PMID- 9000947
TI  - No value for nurses' labours.

PMID- 9000948
TI  - Top of the class.

PMID- 9000949
TI  - Secrets safe with school nurses.

PMID- 9000950
TI  - Poor start on the Finnish line.

PMID- 9000951
TI  - A team approach to the treatment of dysphagia.
AB  - This paper looks at dysphagia and the difficulties it causes for patients and
      those caring for them. It describes an initiative developed to ensure a
      consistent multidisciplinary approach to management of patients with dysphagia.

PMID- 9000953
TI  - Skin 2.

PMID- 9000952
TI  - Eating, ethics and Alzheimer's.
AB  - This article describes a situation in practice where the patient's difficulties
      in swallowing became an ethical dilemma for her family and the author. The
      incident caused the author to reflect on practice and look for ways to improve,
      by reviewing the relevant literature.

PMID- 9000954
TI  - The role of steering groups and project workers in NDUs.
AB  - In light of the challenges that many nursing development units (NDUs) have faced
      during the past four years, this paper assesses the usefulness, as perceived by
      their clinical leaders, of support structures that had to be in place to secure
      NDU status. The structures assessed were a steering group and the allocation of a
      project worker by the King's Fund. Well organised steering groups offer unique
      opportunities to the NDUs to gain access to the knowledge and expertise of key
      figures, marketing the NDU and ensuring the project progresses to plan.
      Influential project workers were found to support the clinical leader and NDU
      staff, act as an external advocate and provide a global knowledge of nursing
      developments. This is the second of two papers reporting on a Department of
      Health-funded review of NDUs. The first appeared in Nursing Times on November 20.

PMID- 9000955
TI  - Economies of scales.

PMID- 9000956
TI  - Left hanging on.

PMID- 9000957
TI  - The right track.

PMID- 9000958
TI  - Advantageous liaisons.

PMID- 9000959
TI  - Wound cleansing.

PMID- 9000960
TI  - Unhealthy relations.

PMID- 9000963
TI  - Depression in primary care. Professional issues.

PMID- 9000962
TI  - Learning curve.

PMID- 9000961
TI  - Nurses take the lead.

PMID- 9000964
TI  - Backlash. A minority quibble.

PMID- 9000965
TI  - Drip by drip...

PMID- 9000966
TI  - Hidden face of harassment.

PMID- 9000967
TI  - Bug busters.

PMID- 9000968
TI  - Just go with the flow.

PMID- 9000969
TI  - Let's go surfing now ... everybody's surfing now.

PMID- 9000970
TI  - Patient power in the net. Interview by Alison Whyte.

PMID- 9000971
TI  - Home intravenous therapy for bronchiectasis patients.
AB  - Home intravenous therapy is the fastest growing area of health care in the USA
      and the Netherlands. This article examines the introduction of this form of
      treatment for a specific client group by the respiratory unit at the Glenfield
      Hospital.

PMID- 9000973
TI  - Making sense of bowel preparation.
AB  - Investigation and surgery of the gastrointestinal tract requires careful
      preparation to ensure success of the procedure and a recovery that is free from
      complications. Different parts of the tract require different preparation. This
      article outlines the principles of bowel preparation and examines some of the
      approaches and agents used.

PMID- 9000974
TI  - A chance for community nurses to shape the health agenda.
AB  - Low morale among community nurses has been well documented. Such demoralisation
      may be caused by a climate of continuous organisational change and financial
      stringency. The author argues, however, that there are many opportunities for
      community nurses to influence local and national health care agendas. She urges
      nurses to diversify in response to current demands.

PMID- 9000972
TI  - Examine your motivation to help and care for others ... (continuing education
      credit).
AB  - Health care professionals are influenced by a number of factors. The way they see
      their roles with respect to the people they help influences the way they behave.
      Patients too have expectations of those who help them which in turn affects the
      way professionals behave. This article invites the reader to examine his or her
      own motivation and attitudes and to consider the experience of people who need
      the help of health care professionals.

PMID- 9000975
TI  - Cloaked in a tattered illusion.

PMID- 9000976
TI  - Last among equals.

PMID- 9000977
TI  - Too slap happy.

PMID- 9000978
TI  - All work and no play....

PMID- 9000980
TI  - Infection control. Revealing answers.

PMID- 9000979
TI  - Infection control. Watching brief.

PMID- 9000981
TI  - Professional development. Cardiopulmonary resuscitation: knowledge for practice
      (continuing education credit).

PMID- 9000982
TI  - Availability of HIV testing for pregnant women.

PMID- 9000983
TI  - Mind games.

PMID- 9000985
TI  - Without a shadow of a doubt. Interview by Lynn Eaton.

PMID- 9000984
TI  - Fault on the line of command.

PMID- 9000986
TI  - Coaching for life.

PMID- 9000988
TI  - Improving the management of children's pain in A&E.
AB  - This paper describes a project that sought to improve the management of
      children's pain in an A&E department. Pain management is not always seen as a
      priority in A&E departments. The problems are highlighted through two case
      studies, and guidelines to improve practice were developed in collaboration with
      a specialist multidisciplinary team.

PMID- 9000987
TI  - Hear my plea.

PMID- 9000989
TI  - Systems of life. Skin 1.

PMID- 9000990
TI  - Principles and practice of blood gas measurement.
AB  - Homeostasis in the human body is maintained by a sophisticated process of
      chemical balance. The disorder of this balance results in ill health. The body
      has its own compensatory mechanisms but intervention may also be required. Blood
      gas analysis is the primary means of assessing acid base balance and is
      frequently required in both acute and chronic illness to assess and determine
      treatment. This article outlines the principles involved in blood gas analysis
      and acid base balance.

PMID- 9000991
TI  - Breast cancer: family under stress.

PMID- 9000992
TI  - A new vision of professionalism.

PMID- 9000993
TI  - Time to get serious.

PMID- 9000995
TI  - Know how: wound management in neonates.

PMID- 9000994
TI  - Wound care. All you need to know about ... maggots.

PMID- 9000996
TI  - Wound care. Larvae help debridement.

PMID- 9000997
TI  - Wound care. Complex conditions.

PMID- 9000998
TI  - Professional deveploment. Cardiopulmonary resuscitation: the role of the nurse
      (continuing education credit).

PMID- 9000999
TI  - [Understanding and trust in our professional group...].

PMID- 9001000
TI  - [Public relations in nursing].

PMID- 9001001
TI  - [Nurses between orders from outside and self determination].

PMID- 9001002
TI  - [Public relations--solid quality of care as a basis for convincing public
      relations in the hospital].

PMID- 9001003
TI  - [My experiences with patient care planning and its conversion into practice].

PMID- 9001004
TI  - [A study tour to The Netherlands].

PMID- 9001005
TI  - [In the nursing profession the general belief is that patients are in the center
      of nursing care. Is that correct? Human relations under nursing conditions].

PMID- 9001006
TI  - [The relationship between nursing and medicine].

PMID- 9001007
TI  - [Humor in the helping relationship].

PMID- 9001008
TI  - [Time out, night work and shift work and overtime. Basic structures of
      legislation on working time. II].

PMID- 9001009
TI  - [Stoma therapy].

PMID- 9001010
TI  - [Barrier-free living allows for a life without exclusion even in old age].

PMID- 9001011
TI  - [Encouraging stoma-bearers to continue living].

PMID- 9001012
TI  - [Patient's requirement as to modern materials for ostomy care].

PMID- 9001013
TI  - [Fighting backache with mobility].

PMID- 9001014
TI  - [Series Self-Care for Nurses. 8. This way you can reinforce your prevention of
      infection].

PMID- 9001015
TI  - [Organ transplantation--pro and contra: ignorance and diffuse fears are defining
      the discussion].

PMID- 9001016
TI  - [Organ removal from cadavers. Brain death is disputed as a safe sigh of death].

PMID- 9001018
TI  - [Study of conventional education? The training of nursing teachers must not
      depend on differing interests].

PMID- 9001017
TI  - [Germans from other countries and Vietnamese are studying geriatric care in the
      IFAG, Berlin: "For some Germans the teachers are pigs"].

PMID- 9001019
TI  - [Nursing performance--supply and demand should be balanced].

PMID- 9001020
TI  - [Project management in the hospital. Lean management puts the coworker in the
      center].

PMID- 9001021
TI  - [Nursing education at St. Mary's Hospital in Muhlheim on the Ruhr. Acting instead
      of waiting is the motto of the reorganization].

PMID- 9001022
TI  - [Day time rehabilitation. Nurses are important members of the team].

PMID- 9001023
TI  - [Nursing courses in Germany: Berlin offers academic training for teachers in the
      health professions].

PMID- 9001024
TI  - [Ethics and the intensive care unit].

PMID- 9001025
TI  - [Let actions speak].

PMID- 9001026
TI  - [Preventive health in childhood].
AB  - A study evaluating use, compliance and activities of a child health care program
      at a health center in Granada. The data, taken over a period of five years,
      showed that 75.2% of one month old infants and 94% of three month old infants
      used the program. The three month old group showed the highest rate of
      compliance, where as the group of two year old infants had the lowest. Clinical
      visits demonstrated a high level of use, between 84-100%. Data about lactating
      mothers and vaccinations showed a low number of patients recorded, which is
      similar to the data published in other journals.

PMID- 9001027
TI  - [Disuse syndrome].

PMID- 9001028
TI  - [Backache in nurses. Prevention].

PMID- 9001029
TI  - [Secondary pneumonia. It can be prevented by care].
AB  - An oncology nursing team at the Freiburg University Hospital have developed a
      detection and prevention plan for respiratory complications. The plan was
      originally applied only to oncology patients, but due to its positive results it
      has since been put in practice in other parts of the hospital. Each patient that
      enters the hospital fills out a medical survey that is used as a baseline to
      decide what level of risk the patient presents in acquiring a respiratory
      infection during their hospitalization. A point system obtained from the survey
      is evaluated on a scale that allows the nursing care to be adjusted accordingly.

PMID- 9001030
TI  - [Bibliometric study of articles published in 3 Spanish reviews from 1991 to
      1993].

PMID- 9001031
TI  - [Educational project 1996-1997].

PMID- 9001032
TI  - [Ergonomics and occupational health (III). The case of hospital staff].

PMID- 9001033
TI  - [The left nasal cavity, superior, inferior and lateral walls].

PMID- 9001034
TI  - [Systems of nasal lavage].

PMID- 9001035
TI  - [Continuing education. Acute myocardial infarction].

PMID- 9001036
TI  - [A functional dressing (taping)].

PMID- 9001037
TI  - [Today's concept and design of hospital space].

PMID- 9001038
TI  - [Iron in childhood].
AB  - The role and function of iron in food is reviewed. The distribution of this
      element in the human body is studied along with: age requirements, the dietetic
      sources of iron, mechanism of absorption and the problems of iron deficiencies.
      Methods that can be taken, in accordance with the College of Nursing, are given
      that may prevent situations of nutritional deficiency and anemia.

PMID- 9001040
TI  - [Nursing care in Down syndrome].

PMID- 9001039
TI  - [Quality control in non-insulin dependent diabetes mellitus. Comparative study in
      2 primary care centers].
AB  - Diabetes Mellitus is a health problem of grave importance. It is of fundamental
      concern that the patient assumes the principle responsibility for his treatment
      under the direction of a health care team, particularly nursing personnel.
      Presented here is a comparative study of recorded clinical histories from two
      primary care centers (Ambulatory/Health Care Center) of patients with diagnoses
      of NIDDM. The histories were chosen by simple random sample. The calculations of
      the sample were performed by the EPIINFO computer program with the following
      results: AMBULATORY: Population size: 683; 95% Level of Confidence; SAMPLE SIZE:
      246 histories. HEALTH CARE CENTER: Population size: 224; 95% Level of Confidence;
      Calculated SAMPLE SIZE: 141 histories. The design is based on R. Heather Palmer's
      cycle of guaranteed quality, as well as the classification of Donabedian and the
      consensus of the nursing teams from the two centers regarding criteria of
      quality. Thus, a comparison was made between what was recorded and what should
      have been done. The obtained results point out a significant difference between
      the Ambulatory Clinic and the Health Care Center. Of major interest is the
      difference in the HbA1 levels (19.1 Health Care Center/0.4 Ambulatory) as well as
      the self evaluation notebooks (33% Health Care Center/0.8% Ambulatory).

PMID- 9001041
TI  - [Professional satisfaction of nurses. A study in area 10 of the Madrid INSALUD].

PMID- 9001042
TI  - [Continuing nursing education at the Virgen de Rocio University Hospital].

PMID- 9001043
TI  - [Hemodialysis and the quality of life. Function of the length of treatment].

PMID- 9001045
TI  - [Naso-gastro-jejunal intubation (stay-put)].

PMID- 9001044
TI  - [Care of the woman and her partner before birth].

PMID- 9001046
TI  - [The lateral wall of the nasal cavity (without the median cartilage to show the
      median meatus)].

PMID- 9001047
TI  - [Atheroma].

PMID- 9001048
TI  - [Decubitus ulcers ... again and always].
AB  - This article is the result of a comparative study during 1994 and 95 concerning
      escar prevalence in our Nephrology intensive care unit. Combined paramedical and
      medical activities concerning preventive and curative care, structured assessment
      (...), made it possible to decrease escar' prevalence from 19% (1994) to 12%
      (1995).

PMID- 9001049
TI  - [Nursing diagnosis].

PMID- 9001051
TI  - [Veronique, nurse and "medical technical counselor". Interview by Odile Burrus].

PMID- 9001050
TI  - [Current stakes in occupational medicine].

PMID- 9001053
TI  - [Anne, Elisabeth, nurses in an inter-enterprise service].

PMID- 9001052
TI  - [Dominique, a nurse responsible to the SNCF].

PMID- 9001054
TI  - [Dorothee and Marie-Danielle, nurses within enterprises].

PMID- 9001055
TI  - [Activity in place plus education: an increasing challenge].

PMID- 9001057
TI  - [A known nuisance, recognized again ... asbestos].

PMID- 9001056
TI  - [Biological agents? A new professional risk].

PMID- 9001058
TI  - [How to reconcile heart disease with work?].

PMID- 9001059
TI  - [Influenza and vaccine: think about it all year long...].

PMID- 9001060
TI  - [Alternative medicine: healing or illusion?].

PMID- 9001061
TI  - [The role of measures of personal hygiene in the prevention of infections in
      autologous bone marrow transplantation. Results of a randomized prospective
      study].
AB  - The paper reports on the results of a prospective, randomized trial in which two
      different regimens of personal hygiene procedures have been compared in 30
      patients undergoing autologous bone marrow transplantation. The main aim of the
      study was to evaluate the incidence of infectious episodes in patients enrolled
      in the trial arm with the simplified hygiene protocol as compared to the standard
      one, used in our Unit for patients undergoing allogenic transplant. No
      significant differences between the two study groups in the incidence of
      infectious episodes or of positive skin cultures were found. Therefore, we
      suggest that a simplified hygiene protocol is as effective as the standard one in
      preventing infectious complications in patients undergoing autologous bone marrow
      transplantation.

PMID- 9001062
TI  - [Psychological and social support for patients with mastectomies].
AB  - Cancer patients need general emotional support but doctors and nurses often fail
      to recognise patients needs. This literature review aims at demonstrating the
      effect of social and psychosocial support on breast cancer women. All the article
      published from 1980 were reviewed. Psychotherapeutic counselling and psychosocial
      interventions were given by a range of people, including nurses, psychologists,
      psychiatrists and volunteers. Unfortunately the poor quality of the studies,
      which are often small and poorly controlled, does not allow to make a definitive
      statement on the impact of psychosocial interventions. The multiplicity of types
      of intervention and outcomes used make comparisons between studies difficult.
      However, when considered in conjunction with the evidence that informal social
      support from partners, friends and relatives is associated with better outcomes,
      this research highlights the importance of psychosocial factors for breast cancer
      patients.

PMID- 9001064
TI  - [Methods and instruments of research. Analysis of various articles].
AB  - Research papers published on some of the most well known medical and nursing
      journals are presented and discussed. The main aim of the contribution, which
      opens an arena for discussion on the Rivista dell'Infermiere is to critically
      appraise published research works focusing both on strengths and novelty as well
      as weaknesses in the hypothesis formulation, methods and instruments used,
      discussion of results. A critical analysis should enable nurses to start learn to
      read and eventually write a research protocol, possibly avoiding some common
      mistakes.

PMID- 9001063
TI  - [Experimenting curing-caring experimenting. Notes to prevent confusion].
AB  - Children, as well as adults, can be subjects of clinical trials. An overview of
      the history and development of clinical experimentation through the main
      scientific publications is briefly outlined. A chart of children rights is also
      presented and discussed. Children's rights range from the right of being included
      in clinical trials to the right of being participants in a research that
      complies, without being overwhelmed, with formal rules. The maximum respect for
      the child is assumed if innovative questions are asked and independence and
      autonomy of judgement of researches are observed.

PMID- 9001065
TI  - [Case report: when the clinic interferes with life].

PMID- 9001066
TI  - [Indicators for the quality of care].

PMID- 9001067
TI  - [A propos of support ... of drugs and ... not only...].

PMID- 9001068
TI  - [Children in search for "women with big eyes"].

PMID- 9001069
TI  - Considering a new product? Put it to a test.

PMID- 9001070
TI  - Ventilation therapy. Flashback!

PMID- 9001071
TI  - I'm a born-again diabetic.

PMID- 9001072
TI  - When this rare cancer strikes.

PMID- 9001073
TI  - New pins in the RN collection.

PMID- 9001075
TI  - How homeopathy works.

PMID- 9001074
TI  - What's wrong with this patient? Psittacosis.

PMID- 9001076
TI  - Safeguard your license: avoid these pitfalls.

PMID- 9001077
TI  - The FDA warns of the dangers of ephedrine.

PMID- 9001078
TI  - If therapeutic touch works, prove it!

PMID- 9001079
TI  - [Suffering and the appreciation of life].

PMID- 9001080
TI  - [It is difficult to talk about drugs. Information and orientation from community
      resources].

PMID- 9001081
TI  - [Education for the primary prevention of substance dependence].

PMID- 9001082
TI  - [Substance dependence--repercussions for maternal-child health. Newborn children
      of substance-dependent mothers].

PMID- 9001083
TI  - [Substance dependence. Evaluation of risk and planning of care].

PMID- 9001084
TI  - [Peer education: adolescent to adolescent progRam].

PMID- 9001085
TI  - [The 4 stages of substance dependence].

PMID- 9001086
TI  - [Health care teams in the prevention and reintegration of substance dependent
      adolescents].

PMID- 9001087
TI  - [Portuguese women and their role in the prevention of substance dependence].

PMID- 9001088
TI  - [Heroin substitutes. Daily dose].

PMID- 9001089
TI  - [Progress in the fight against alcohol and drugs].

PMID- 9001090
TI  - [Nursing regulations about the exercise of the profession].

PMID- 9001091
TI  - [Standardized geriatric evaluation. An efficient method for the prevention of
      dependency].

PMID- 9001093
TI  - [Drugs for the elderly. How to administer them?].

PMID- 9001092
TI  - [From a subjective evaluation to a multidimensional one].

PMID- 9001094
TI  - [Severe fall with head injury].

PMID- 9001095
TI  - [Dental prosthesis. Dental hygiene is important].

PMID- 9001096
TI  - [Nutritional evaluation of the elderly patient. A much used test: the mini
      nutritional assessment (MNA)].

PMID- 9001097
TI  - [Dementia and/or depression].

PMID- 9001098
TI  - [Meals in geriatric institutions. Reflections on a different scene].

PMID- 9001100
TI  - [Chart of rights and freedoms].

PMID- 9001099
TI  - [The daily diet].

PMID- 9001101
TI  - [What to do about Alzheimer's disease after the diagnosis].

PMID- 9001102
TI  - [Correctly placing a bedridden patient].

PMID- 9001103
TI  - [Technical aids].

PMID- 9001104
TI  - [Home care services].

PMID- 9001105
TI  - [Ergotherapy in geriatrics].

PMID- 9001106
TI  - [Lighting and the reduction of visual capacity].

PMID- 9001107
TI  - Median nerve suture in the distal part of the forearm. MRI evaluation.
AB  - The aim of the study was to assess MR images of median nerve suture in the distal
      part of the forearm on fresh cadavers and injured patients. The median nerve was
      dissected in the distal one-third of the forearm in four fresh cadaveric
      specimens, divided and repaired in three of them in two cases with 3/0 nylon (one
      with well-apposed edges and the other with a lateral gap) and, in the third
      specimen, with 9/0 nylon with well apposed edges. The course of the median nerve
      was then studied on MR imaging in different planes and the quality of the nerve
      repair was evaluated. A good correlation was found between the MR images and the
      type of nerve suture. These findings were applied in management of two clinical
      cases in whom reexploration and revision of the median nerve repair was carried
      out.

PMID- 9001108
TI  - Incidence and distribution of scaphotrapezotrapezoidal arthritis in 73 fresh
      cadaveric wrists.
AB  - The STT joint was examined in 73 fresh cadaveric specimens (25 male and 48 female
      with an average age of 84 years) with a view to study the incidence and
      characteristics of degenerative changes in this joint. The articular degeneration
      was graded from 0 to 3 according to increasing loss of cartilage and the location
      of the changes was noted. At the same time, the presence and extent of
      concomitant trapezio-metacarpal arthritis was noted. 61 of the 73 hands (83.3%)
      were found to present STT arthritis. Degeneration of the trapezoid articular
      surface was:- more frequent: 53 hands (72.6%) as compared to 48 (65.7%),-of
      greater severity: 40 cases (55%) of grades 2/3 as compared to 25 (34%), than that
      of the trapezium. Concomitant or isolated arthritis in the trapezometacarpal
      joint (90.4%) was present in 66 of the 73 hands (79%) examined with grade 3
      changes in 13 cases. The apparent predominance of degeneration in the scapho
      trapezoidal articulation could, perhaps, lead us to assume that this might be the
      site of origin of STT arthritis. It could also explain the persistence of
      symptoms following prosthetic replacement of the trapezium.

PMID- 9001109
TI  - Ulnar neuropathy caused by a thrombosed ulnar vein. Case report and literature
      review.
AB  - A previously unreported finding of ulnar nerve compression at the wrist caused by
      a thrombosed ulnar artery vena comitans is described. The value of magnetic
      resonance imaging (MRI) in evaluating wrist masses is reviewed.

PMID- 9001110
TI  - Surgical treatment of Madelung disease by the Sauve-Kapandji technique.
AB  - The Madelung deformity, a congenital alteration of growth in the distal radial
      epiphysis, becomes evident during adolescence, producing serious esthetic and
      functional disturbances. From 1982 to 1991, 15 patients ranging from 16 to 23
      years old, suffering from Madelung deformity were operated by the Sauve-Kapandji
      surgical technique (a pseudarthrosis is created on the ulna and an arthrodesis on
      the distal radio ulnar joint). The esthetic appearance and grip strength were
      improved. Pain was eliminated and the incidence of complications was very low.

PMID- 9001111
TI  - The influence of a biological therapy on physicians' narratives and
      interrogations: the case of general paralysis of the insane and malaria fever
      therapy, 1910-1950.

PMID- 9001112
TI  - Two models for human genetics: blood grouping and psychiatry in Germany between
      the World Wars.

PMID- 9001113
TI  - Sigerist in Saskatchewan: the quest for balance in social and technical medicine.

PMID- 9001114
TI  - Professions in process.

PMID- 9001115
TI  - Fatal Falciparum malaria in Canadian travellers.

PMID- 9001116
TI  - Malaria--boundary health unit, British Columbia, 1995.

PMID- 9001117
TI  - Request for research proposals. Division of STD Prevention and Control, bureau of
      HIV/AIDS and STD, Laboratory Centre for Disease Control.

PMID- 9001118
TI  - Obesity update 1996 fails to convince.

PMID- 9001119
TI  - The sun should not rise or set on a patient with mechanical obstruction.

PMID- 9001120
TI  - Capitation: a moral issue in the managed care paradigm.

PMID- 9001121
TI  - Colitis induced by non-steroidal anti-inflammatory drugs.

PMID- 9001122
TI  - Neurodevelopmental outcome of extremely low birth weight infants in Maryland.
AB  - The survival rate of extremely low birth weight (ELBW; i.e. < 1001 grams) infants
      has significantly improved in the past 10 years secondary to the numerous
      advances in neonatology. There have been many favorable reports of the
      neurodevelopmental outcomes of survivors, but the studies often span several
      years to collect sufficient number of subjects. This study assesses the outcome
      of 100 ELBW infants born in Maryland in 1990 and analyzes factors that may have
      contributed to their outcomes at one year corrected age. Of this group, 72% had
      no evidence of severe disability (e.g., cerebral palsy (CP) or mental retardation
      (MR); however, 51% of the children had abnormal or suspect neurological
      examinations, and 24% had CP. Eighteen percent of the children were more than one
      standard deviation below the mean cognitively; 30% were below normal for motor
      abilities, and 33% were below normal for language abilities. Prior to this study,
      many of these children were not recognized by their primary physician as having
      any developmental problems. Many of these children were not followed in neonatal
      intensive care unit (NICU) follow-up programs, and most were not receiving
      appropriate early intervention services (EIS). Previous studies have associated
      different neonatal events with the risk of developmental delay. Bronchopulmonary
      dysplasia (BPD) and periventricular leukomalacia (PVL) accounted for most of the
      variance of this sample's developmental outcome. Of these 100 ELBW infants, 56
      received surfactant. Analysis demonstrated no significant differences in
      developmental outcomes between those who received surfactant and those who did
      not. However, those who received rescue surfactant were more likely to acquire a
      diagnosis of BPD. As demonstrated by this study, ELBW infants are at risk for
      significant developmental problems. This supports the need for targeted outreach,
      developmental monitoring, early intervention services, and parent support and
      education.

PMID- 9001123
TI  - Improving the use of advance directives.
AB  - Advance directives are a valuable form of medical planning and well-accepted by
      patients. They are part of preventive health care and should be included as
      routine care. Completion of these documents is a process requiring
      patient/physician communication and can be effectively completed over several
      visits. Periodic reassessment of patient attitudes is important. Finally,
      including these documents in the patient record and communication of this
      information is important, as it helps shepherd the patient through the medical
      system. Physician investment in the use of advance directives is minimal, while
      the rewards are prodigious.

PMID- 9001124
TI  - Cardiovascular surgery. The Maryland State Medical Journal 1956.

PMID- 9001125
TI  - Outpatient detoxification of a drug abuser: the case of Dr. A.

PMID- 9001126
TI  - Phronesis in clinical ethics.
AB  - This essay argues that while we have examined clinical ethics quite extensively
      in the literature, too little attention has been paid to the complex question of
      how clinical ethics is learned. Competing approaches to ethics pedagogy have
      relied on outmoded understandings of the way moral learning takes place in
      ethics. It is argued that the better approach, framed in the work of Aristotle,
      is the idea of phronesis, which depends on a long-term mentorship in clinical
      medicine for either medical students or clinical ethics students. Such an
      approach is articulated and defended.

PMID- 9001127
TI  - Discretionary power, lies, and broken trust: justification and discomfort.
AB  - This paper explores the relationship between the bonds of practitioner/patient
      trust and the notion of a justified lie. The intersection of moral theories on
      lying which prioritize right action with institutional discretionary power allows
      practitioners to dismiss, or at least not take seriously enough, the harm done
      when a patient's trust is betrayed. Even when a lie can be shown to be justified,
      the trustworthiness of the practitioner may be called into question in ways that
      neither theories of right action nor contemporary discourse in health care
      attends to adequately. I set out features of full trustworthiness along
      Aristotelian lines.

PMID- 9001128
TI  - The social concept of disease.
AB  - In the discussion of such social questions as "how should alcoholics be treated
      by society?" and "what kind of people are responsible in the face of the law?",
      is "disease" a value-free or value-laden notion, a natural or a normative one? It
      seems, for example, that by the utterance "alcoholism should be classified as a
      disease' we mean something like the following: the condition called alcoholism is
      similar in morally relevant respects to conditions that we uncontroversially
      label diseases, and therefore we have a moral obligation to consider alcoholism a
      disease. So there are grounds to think that, in the discussion of social
      questions, our concept of disease is strongly value-laden. However, it does not
      follow that the medical concept of disease is likewise value-laden. In this paper
      I distinguish between the medical and social concepts of disease, arguing that
      the naturalist-normativist debate is concerned with the former, but not the
      latter. Therefore, we need not settle the naturalist-normativist debate in order
      to conclude that the social concept of disease is value-laden.

PMID- 9001129
TI  - About signs and symptoms: can semiotics expand the view of clinical medicine?
AB  - Semiotics, the theory of sign and meaning, may help physicians complement the
      project of interpreting signs and symptoms into diagnoses. A sign stands for
      something. We communicate indirectly through signs, and make sense of our world
      by interpreting signs into meaning. Thus, through association and inference, we
      transform flowers into love, Othello into jealousy, and chest pain into heart
      attack. Medical semiotics is part of general semiotics, which means the study of
      life of signs within society. With special reference to a case story, elements
      from general semiotics, together with two theoreticians of equal importance, the
      Swiss linguist Ferdinand de Saussure and the American logician Charles Sanders
      Peirce, are presented. Two different modes of understanding clinical medicine are
      contrasted to illustrate the external link between what we believe or suggest, on
      the one hand, and the external reality on the other hand.

PMID- 9001130
TI  - The gastroenterologist and his endoscope: the embodiment of technology and the
      necessity for a medical ethics.
AB  - The purpose of this essay is to argue for the necessity of an ethics of the
      practice of the specialist-technologist in medicine. In the first part I sketch
      three stages of medical ethics, each with a particular viewpoint regarding the
      technology of medicine. I focus on Brody's consideration of the "physician's
      power" as a example of contemporary medical ethics which explicitly excludes the
      specialist-technologist as a locus of development of medical ethics. Next, the
      philosophy of Heidegger is examined to suggest an approach to the problem, and,
      finally, some of Levinas' contributions regarding the "other" are introduced to
      suggest a preliminary approach to a medical ethics of the specialist
      technologist.

PMID- 9001131
TI  - Freedom and democracy in health care ethics: is the cart before the horse?

PMID- 9001133
TI  - Morphological findings after intracoronary application of endothelin-1 in dog.
AB  - BACKGROUND: Endothelin-1 is a strong vasoconstrictor, high doses of which can
      cause prolonged vasoconstriction. MAIN PURPOSE: The aim of our study was to
      investigate as to whether the endothelin-induced vasoconstriction causes
      irreversible morphological changes in the myocardium in experimental animals and
      to verify the applicability of this experimental model in the study of the impact
      of endothelin. METHODS: Fourteen anaesthetized dogs were administered with 400
      pmol of endothelin. The substance was applied into the left anterior descending
      coronary artery. The serum activities of AST, CK and LD enzymes, and changes in
      electric activity of the myocardium were monitored. The heart of one of the dogs
      was analyzed morphologically. RESULTS: Following the application of endothelin,
      vasoconstriction supervened, lasting from 25 to 27 minutes. Five dogs developed
      fibrillation of ventricles and died. The dogs which survived yielded changes in
      the activities of the investigated enzymes and changes in electric activity which
      were typical of focal impairment of the myocardium in sense of necrosis.
      Morphologically the changes represented disseminated fibrosis or minor scars in
      the myocardium. CONCLUSIONS: Application of endothelin into the coronary artery
      can cause irreversible structural changes in the myocardium. (Fig. 1, Ref. 18.).

PMID- 9001132
TI  - [The cytoprotective effect of magnesium in global myocardial ischemia].
AB  - BACKGROUND: Administration of magnesium in the therapy of ischaemic heart
      diseases does not belong to the standard procedures. The results of clinical
      trials with application of this cation are mutually contradictive, mechanisms of
      its effect are not solved yet. Many physicians consider magnesium to represent a
      classical placebo, or an uncertain light sedative. MAIN PURPOSE AND OBJECTIVES:
      The study is aimed at proving the direct effect of magnesium on the heart muscle
      under ischaemic conditions which exclude the placebo effects. These conditions
      are mostly fulfilled by the model of isolated heart. MATERIAL AND METHODS: The
      authors used isolated rabbit hearts according to Langedorff with Krebs-Henseleit
      (KH) perfusion solution, the only variable of which is represented by
      concentration of magnesium. The following groups of patients were formed: 1.
      Control group-30-minute perfusion with normal Mg concentration (0.5 mmol/l) in KH
      solution. 2. Hypomagnesemia-30-minute perfusion with KH solution Mg-free. 3.
      Normomagnesemia+ischaemia-30-minute perfusion with normal concentration succeeded
      by a 60-minute global ischaemia. 4. Hypomagnesiaemia+ischaemia-30-minute
      perfusion with KH solution magnesium-free succeeded by a 60-minute global
      ischaemia. 5. Hypermagnesiemia +ischaemia-30-minute perfusion with increased Mg
      concentration in KH solution to 2.0 mmol/l succeeded by a 60-minute global
      ischaemia. The investigated parameters: after completion of perfusion the authors
      isolated mitochondria and evaluated individual parameters of oxidative
      phosphorylation by means of oxygraph/Gilson/with Clark's oxygen electrode. The
      calcium uptake by mitochondria was observed by means of calcium-sensitive
      electrode Orion (oxygraph Gilson). The formation of free oxygen radicals was
      observed indirectly by spectrophotometric assessment of malondialdehyde
      production. Concentration of mitochondrial nucleotides (AMP, ADP, ATP) was
      assessed by using HPLC. RESULTS: Hypomagnesemia lasting 30 minutes had a negative
      effect on the index of oxidative phosphorylation (ADP:O p < 0.005) the uptake of
      calcium (p < 0.002), ATP concentration in mitochondrial ATP (p < 0.05) and the
      production of free radicals significantly increased (p < 0.001). Normomagnesemia
      indicated practically no cytoprotective effect before global ischaemia of
      myocardium lasting for 60 minutes. Hypermagnesemia indicated a direct
      cytoprotective effect before global ischaemia affecting respiration of isolated
      heart mitochondria in state of S3 (p < 0.001), respiration control index RCI (p <
      0.001), the rate of oxidative phosphorylation OPR (p < 0.001) and on the index of
      oxidative phosphorylation ADP:O (p < 0.05) on the uptake of calcium by
      mitochondria (p < 0.002) and on concentration of mitochondrial nucleotides ATP (p
      < 0.002). It was remarkable that also under conditions of moderate hypomagnesemia
      the production of malondialdehyde increased. CONCLUSIONS: Under our experimental
      conditions it was confirmed that magnesium yields direct cytoprotective effect on
      the subcellular level of the myocardium prior to global ischaemia, providing the
      process takes place under the condition of hypermagnesemia. (Tab. 1, Fig. 12,
      Ref. 45.) Key words: hypomagnesemia, normomagnesemia, hypermagnesemia,
      Langendorff's global ischaemia, mitochondrial metabolism, cytoprotective effect.

PMID- 9001134
TI  - Morphological changes in the ewe uterine tube (oviduct) epithelium during
      puerperium.
AB  - The aim of our investigations was to describe the morphological changes in the
      epithelium of the ampulla region of the ewe uterine tube ampulla on days 2, 7,
      17, 25 and 34 post partum. Shortly after the parturition the epithelium was low.
      Ciliated cells were dark with few kinocilia and secretory cells were light in
      colour and contained no secretory granules. On days 17 and 25 post partum the
      ciliated cells were high. They had well-developed granular endoplasmic reticulum,
      ribosomes, and developing basal corpuscles and kinocilia. Secretory cells
      contained a well-developed Golgi complex, granular endoplasmic reticulum and
      numerous secretory granules of varied size, shape, and density. On day 34 post
      partum, the ciliated cells had numerous kinocilia on their apical surface.
      Secretory cells released their product into the oviduct lumen through pores or
      high protrusions of cells detached, decomposed, and became the part of the
      secretion.

PMID- 9001135
TI  - Mutagenicity of feeds and bovine milk in districts with different levels of
      environmental pollution.
AB  - Mutagenic activities of feedstuffs and bovine milk were investigated by the Ames
      test in two districts of the Czech Republic (Teplice and Prachatice), differing
      in the levels of industrial pollution. Salmonella typhimurium strains TA 98 and
      TA 100 with or without metabolic activation were used in the tests. Samples of
      currently fed feedstuffs and milk were collected in both districts in the spring
      1992, autumn 1992, spring 1993, and autumn 1993. The Teplice and Prachatice sets
      included 12 and 11 representative samples, respectively. The samples were rinsed
      and extracted with acetone and methanol. Thus each sample was divided into four
      separate samples. The total number of revertants obtained in the industrial
      district Teplice was significantly higher than the corresponding value for the
      Prachatice district. Some between-the-seasons differences were also found within
      each of the two districts. The strain TA 98 proved to be more sensitive in the
      mutagenicity tests than the strain TA 100. Thirty-eight and thirty-one milk
      samples were collected in the districts Teplice and Prachatice, respectively. The
      overall evaluation demonstrated a significant between-the-districts difference in
      the total number of revertants induced by the milk samples in the strains TA 98
      and TA 100.

PMID- 9001136
TI  - Rapid method for isolation of high molecular weight plasmids suitable for
      digestion with restriction endonucleases.
AB  - The described method is a modification of the hot alkaline method (Kado and Liu,
      1981). The modification lies in replacement of SDS with Triton X- 100. The DNA
      purified by this method was readily digested with restriction endonucleases for a
      variety of applications, e. g. restriction analysis of plasmid DNA in
      epidemiological studies, restriction mapping and cloning of high molecular weight
      plasmids, and for identification of transpozon mutants.

PMID- 9001137
TI  - Peak assignment in localized 1H MR spectra of human muscle based on oral creatine
      supplementation.
AB  - 1H-MR spectra of human skeletal muscle feature peak splittings due to dipolar
      coupling. Quantitative difference spectroscopy in a double-blind cross-over trial
      testing oral creatine supplementation revealed that most of the resonances
      affected by dipolar coupling can be assigned to creatine and/or phosphocreatine.
      The assignment was performed in two different skeletal muscles and confirmed by
      measurements at the magic angle where dipolar splittings vanish. Numerical
      spectral simulations revealed that the observed spectra are consistent with
      partly-averaged dipolar coupling among methylene and methyl protons of
      (phospho)creatine. The possible nature of the molecular dynamics leading to
      incomplete dipolar averaging is discussed.

PMID- 9001138
TI  - Simultaneous 3D NMR spectroscopy of proton-decoupled fluorine and phosphorus in
      human liver during 5-fluorouracil chemotherapy.
AB  - Simultaneous acquisition of 1H-decoupled 31P and 19F 3D CSI is demonstrated in
      the liver of a patient undergoing 5-fluorouracil chemotherapy. Both 31P and 19F
      shared the same voxel size (64 or 27 ml), bi-level 1H-decoupling and 0.35 s TR.
      The measurements were done in a 1.5 Tesla clinical imager with three radio
      frequency (RF) channels and a triple-tuned surface-coil. The overall MRI and MRS
      examination time was under 90 min. Simultaneous acquisition of 31P and 19F
      permits localized study of the influence of hepatic metabolism on the uptake and
      catabolism of fluoropyrimidine drugs without extra measurement time or higher
      SAR.

PMID- 9001139
TI  - Neuronal nitric oxide synthase mutant mice show smaller infarcts and attenuated
      apparent diffusion coefficient changes in the peri-infarct zone during focal
      cerebral ischemia.
AB  - Diffusion-weighted MRI at 2 T was used to monitor and assess tissue damage after
      permanent middle cerebral artery occlusion (MCAO) in wild-type (WT) and mice
      deficient in nitric oxide synthase gene expression (nNOS-). The ischemic lesion
      was evaluated 3 h after occlusion and subdivided into the lesion core and peri
      infarct zone based on the magnitude of the apparent diffusion coefficient (ADC)
      change. Infarct volume, measured by using histochemical staining 24 h after MCA
      occlusion, correlated best with MRI infarct volume as assessed by an ADC
      threshold of 25% decrease from baseline at 3 h. For ADC thresholds of greater
      than 25% decrease, lesion size was not significantly different in nNOS- and WT
      mice. However, brain tissue showing ADC decreases of 10-25% was significantly
      smaller in the ipsilateral hemisphere of mutants (27 +/- 2% and 21 +/- 2% in WT
      and nNOS-, respectively; P < 0.05). These findings occurred independently of
      infarct volume and are consistent with a smaller peri-infarct zone in nNOS- mice.
      We postulate that the smaller peri-infarct zone is a reflection of less severe
      metabolic disturbance after ischemia in nNOS- mice, possibly related to
      diminished production of nitric oxide (NO) or a related product. We conclude that
      magnetic resonance techniques previously used to assess ischemic damage in larger
      animals can be extended to the mouse, raising the possibility that the molecular
      mechanisms leading to ischemic damage can be examined by using genetically
      engineered mice.

PMID- 9001140
TI  - The sensitivity of low flip angle RARE imaging.
AB  - It is demonstrated that the stability of the Carr-Purcell-Meiboom-Gill (CPMG)
      sequence reflects the existence of a steady state solution to the Bloch equations
      in the absence of T2 and T1 decay. The steady state theory is then used to
      evaluate the performance of low flip angle RARE imaging sequences with both
      constant and optimally varied refocusing flip angles. The theory is
      experimentally verified in phantoms and then optimized, single shot, low flip
      angle RARE is used to obtain artifact-free images from the brain of a normal
      volunteer.

PMID- 9001141
TI  - In vivo MR microscopy of the human skin.
AB  - The requirements for imaging the skin are dictated by the organ's layered
      structure, which extends only a few millimeters from the surface and thus demands
      extremely high resolution in this direction. While less critical, resolution in
      the remaining two dimensions determines whether the skin's accessory structures
      can be resolved. The problem is compounded by short transverse relaxation times,
      in particular of the dermis, the structure of most clinical interest. In this
      work images of the normal human skin were obtained in vivo at voxel sizes as
      small as 19 x 78 x 800 microm3, by means of customized 3D gradient and partial
      flip-angle spin-echo pulse sequences and very small transmit/receive coils on a
      1.5T clinical imager equipped with high-power whole-body gradients. Structures
      resolved include hair follicles and the sublayers of the dermis. The very short
      time constant for the major component (91%) for transverse relaxation in the
      dermis (T2* approximately 10 ms) suggests the potential of substantial gains in
      achievable signal-to-noise ratio by shortening the echo time.

PMID- 9001142
TI  - In vivo 23Na NMR studies of myotonic dystrophy.
AB  - Myotonic dystrophy is an inherited multi-system disease. Its pathophysiology
      leading to muscle malfunction and damage is not well understood. 23Na NMR
      spectroscopy was applied here for an in vivo comparative study of the calf
      muscles of 7 myotonic dystrophy patients at various stages of the disease and 11
      healthy volunteers. Both the total sodium content, expressed as the ratio of the
      23Na and 1H water signals, and the fast transverse relaxation time, T2f,
      determined from the triple quantum-filtered spectra, increased in correlation
      with the severity of the disease. The results demonstrate that 23Na NMR enables
      the quantitation of myotonic dystrophy progression.

PMID- 9001143
TI  - In vivo observation of anisotropic motion of brain water using 2H double quantum
      filtered NMR spectroscopy.
AB  - The 2H DQF NMR spectra of deuterated water molecules were measured for the first
      time in in vivo rat brain. The observation of the DQF signal indicates that there
      is a water population that exhibits anisotropic motion. The characteristics of
      the DQF spectra premortem and postmortem are very similar (lineshape and
      relaxation times). In the 1st h there is a 10-15% decrease in the signal
      intensity of the DQF spectra followed by a gradual but a much slower decrease in
      the DQF signal intensity that reaches 65-70% of its initial value after only 12
      h. When the brains were kept at 4 degrees C, a 40% decrease in the DQ signal
      intensity was observed only after 7 days. Mechanical chopping of the brain
      tissues causes an immediate loss of more that 97% of the DQ signals. The slow,
      temperature-sensitive decay of the signal, and its sensitivity to mechanical
      treatment point out that these signals originate from water molecules that
      interact with structural components in the brain. The characteristics of the DQF
      spectra depend on the amount of bulk water as exemplified by increased residual
      quadrupolar interaction and relaxation rates obtained when dehydrating the brain
      tissue.

PMID- 9001144
TI  - Proton MR spectroscopy of the normal human prostate with an endorectal coil and a
      double spin-echo pulse sequence.
AB  - This report describes the use of an endorectal coil and a double spin-echo pulse
      sequence for localized 1H MR spectroscopy of the normal prostate in volunteers.
      The spectra showed well-resolved signals for citrate, (phospho)choline, and
      creatine protons. Additional signals were assigned to taurine and myoinositol
      protons. J modulation of the main and outer peaks of citrate could be monitored
      in vivo. Apparent relaxation times T1 and T2 have been estimated for the methyl
      protons of cholines and creatine. An effective T1 relaxation time was estimated
      for the main peaks of the citrate multiplet. Ratios of the integrals of these
      resonances have been evaluated, and tissue contents of choline and creatine were
      estimated using the H2O signal as an internal reference. Spectroscopic imaging
      experiments revealed a lower relative citrate signal in central parts of the
      prostate than in peripheral parts.

PMID- 9001145
TI  - Quantitation of T2' anisotropic effects on magnetic resonance bone mineral
      density measurement.
AB  - In this paper, the authors quantitate the anisotropy of susceptibility effects in
      an uniaxial trabecular bone model and show its relevance to clinical MR bone
      mineral density measurements. A physical model is described that quantitates the
      anisotropic MR behavior of uniaxial trabecular bone. To test the model; a phantom
      of parallel polyethylene filaments was scanned every 15 degrees between 0 degrees
      and 90 degrees with respect to the system's main magnetic field (B0). The distal
      radial metaphysis of a healthy female volunteer was scanned in orthogonal
      projections. The signal from each phantom image and each radial image was
      separated in a pixel-wise fashion into R2 and R2' maps. As predicted, R2'
      relaxation showed anisotropic behavior and changed according to sin2 (theta),
      confirming that columnar structures parallel with B0 will cause no MR
      susceptibility effects. Scans of the distal radius showed that R2' relaxation was
      twice as great with the forearm perpendicular to B0 as when it was parallel to
      it, demonstrating different contributions from struts and columns. For both
      phantom and radial bone scans, R2 relaxation was isotropic and did not change
      with object orientation.

PMID- 9001146
TI  - 1H chemical shift imaging reveals loss of brain tumor choline signal after
      administration of Gd-contrast.
AB  - 1H MR spectra obtained by chemical shift imaging (CSI) of contrast-enhancing
      brain tumors before and after the administration of Gd-contrast agent were
      quantitated and compared with the results in normal brain tissue included in the
      volume of interest. Twenty-seven combined magnetic resonance imaging and
      spectroscopy (MRI, MRS) examinations of brain tumor lesions included T1-weighted
      MRI and CSI (TR/TE 1500/135 ms double-spin echo) repeated 5-10 min after the
      administration of Gd-contrast agent (0.1-0.2 mM). In 1H MR spectra of contrast
      enhancing tumor Gd-contrast induced a mean loss of 15% of the peak area of
      choline-containing compounds (Cho, P < 0.001) that was correlated with
      precontrast Cho linewidth (r = -0.72, P < 0.00001). This phenomenon limits the
      diagnostic use of brain tumor MRS examinations performed immediately after
      contrast-enhanced MRI.

PMID- 9001147
TI  - Correction for vascular artifacts in cerebral blood flow values measured by using
      arterial spin tagging techniques.
AB  - "Vascular" artifacts can have substantial effects on human cerebral blood flow
      values calculated by using arterial spin tagging approaches. One vascular
      artifact arises from the contribution of "tagged" arterial water spins to the
      observed change in brain water MR signal. This artifact can be reduced if large
      bipolar gradients are used to "crush" the MR signal from moving arterial water
      spins. A second vascular artifact arises from relaxation of "tagged" arterial
      blood during transit from the tagging plane to the capillary exchange site in the
      imaging slice. This artifact can be corrected if the arterial transit times are
      measured by using "dynamic" spin tagging approaches. The mean transit time from
      the tagging plane to capillary exchange sites in a gray matter region of interest
      was calculated to be approximately 0.94 s. Cerebral blood flow values calculated
      for seven normal volunteers agree reasonably well with values calculated by using
      radioactive tracer approaches.

PMID- 9001148
TI  - A MRI spatial mapping technique for microvascular permeability and tissue blood
      volume based on macromolecular contrast agent distribution.
AB  - A rapid and automated method for two-dimensional spatial depiction (mapping) of
      quantitative physiological tissue characteristics derived from contrast enhanced
      MR imaging was developed and tested in disease models of cancer, inflammation,
      and myocardial reperfusion injury. Specifically, an established two-compartment
      kinetic model of unidirectional mass transport was implemented on a pixel-by
      pixel basis to generate maps of tissue permeability surface area product (PS) and
      fractional blood volume (BV) based on dynamic MRI intensity data after
      administration of albumin-(Gd-DTPA)30, a prototype macromolecular contrast medium
      (MMCM) designed for blood pool enhancement. Maps of PS and BV in disease models
      of adenocarcinoma, intramuscular abscess inflammation, and myocardial reperfusion
      injury clearly depicted zones of increased permeability (up to approximately 500
      microl/cc/h--compared to <25 microl/cc/h in normal tissues). As revealed on PS
      maps, the rank ordering of studied permeability abnormalities was reperfusion
      injury > inflammation > tumors. A rapid, automated mapping technique derived from
      dynamic contrast-enhanced MRI data can be used to facilitate the identification
      and characterization of pathophysiologic abnormalities, specifically relative
      increases in blood volume and/or microvascular permeability.

PMID- 9001149
TI  - Multiple tuning of birdcage resonators.
AB  - A theoretical framework is presented for designing birdcage resonators for MRI
      and MR spectroscopy. The analogy between the birdcage problem and the phonon
      problem in solid-state physics is used to achieve multiple tuning. Allowing that
      the capacitances in the columns of the cage assume unequal values, it is possible
      to achieve multiple tuning and simultaneously preserve the sinusoidal current
      distribution necessary to set a homogeneous magnetic field. Given the physical
      dimensions of the columns and branches of the cage as well as the desired
      resonant frequencies, the corresponding values of the capacitances can be
      calculated exactly. Closed-form expressions for the capacitances are given in
      terms of the mutual inductances and the desired resonant frequencies. A detailed
      analysis for a symmetrical low-pass birdcage is presented. The expressions for
      the resonant frequencies reduce to those given by other authors when only nearest
      neighbor mutual inductances are included.

PMID- 9001150
TI  - Three-dimensional magnetization-prepared time-of-flight MR angiography of the
      carotid and vertebral arteries.
AB  - Three-dimensional magnetization-prepared (MP) MR angiography (MRA) was applied to
      the carotid and vertebral arteries by using ECG triggering, a slab selective RF
      inversion pulse, centric phase encoding and acquisition during diastole. Both
      theoretically and experimentally, the MP MRA sequence was shown to perform well
      in cases where there was substantial blood replenishment during the inversion
      time TI (>330 ms). In comparison with standard, ungated, steady-state 3D time-of
      flight MRA in 13 consecutive volunteers, the MP MRA images demonstrated better
      background suppression with less artifact and generally had more uniform vessel
      depiction. The MP MRA sequence was generally superior for portraying vessels
      exhibiting high pulsatility such as the carotid siphon. However, in distal
      vessels with slow flow and incomplete blood replenishment, the MP MRA technique
      was inferior due to increased loss of vessel signal. The reasons for this
      increased signal loss are identified and improvements to the MP MRA sequence are
      suggested.

PMID- 9001153
TI  - Characterization of and correction for artifacts in linogram MRI.
AB  - Chemical shift differences, field inhomogeneity, and gradient nonlinearity result
      in artifacts in magnetic resonance imaging. Three artifacts are characterized for
      linogram imaging and it is shown that, based on computer simulations and theory,
      linogram MRI behaves similarly to 2DFT. A correction technique similar to a
      scheme for 2DFT imaging based on the Dixon technique and coordinate transform
      methods is proposed. The algorithm is applied to correct for field inhomogeneity
      and gradient nonlinearity-induced artifacts in both simulations and images of a
      clinical phantom. The results show good correlation with the theory. It is
      concluded that linogram imaging offers certain attractive features of both 2DFT
      and PR imaging techniques, and is a potentially viable alternative to PR imaging
      in the presence of field inhomogeneity.

PMID- 9001152
TI  - Improvement of brain lesion detection at 0.1 T by simultaneous use of Gd-DTPA and
      magnetization transfer imaging.
AB  - Imaging parameters were optimized at 0.1 T to improve contrast-to-noise ratios
      (CNR) when combining magnetization transfer (MT) imaging and the use of
      paramagnetic contrast medium. This was accomplished by imaging a phantom
      containing serial concentrations of Gd-DTPA in cross-linked bovine serum albumin.
      With the use of simulations, the dependence of CNR on imaging parameters was
      studied. Conventional and MT images were obtained from 10 brain tumor patients
      with single and triple doses of Gd-DTPA. Simulations demonstrated the importance
      of TR in postcontrast sequences. The CNR in MT images is less sensitive to TR
      than in conventional images. A significant CNR improvement caused by MT remains
      at longer TR when there is no contrast enhancement without MT. The clinical
      results indicate that a single dose of Gd-DTPA combined with MT cannot replace
      imaging with a triple dose. However, MT significantly improved the CNR after
      single and triple Gd-DTPA-doses on T1-weighted and proton-density images.

PMID- 9001155
TI  - The b matrix in diffusion tensor echo-planar imaging.
AB  - In diffusion tensor imaging (DTI) an effective diffusion tensor in each voxel is
      measured by using a set of diffusion-weighted images (DWIs) in which diffusion
      gradients are applied in a multiplicity of oblique directions. However, to
      estimate the diffusion tensor accurately, one must account for the effects of all
      imaging and diffusion gradient pulses on each signal echo, which are embodied in
      the b matrix. For DTI to be practical clinically, one must also acquire DWIs
      rapidly and free of motion artifacts, which is now possible with diffusion
      weighted echo-planar imaging (DW-EPI). An analytical expression for the b matrix
      of a general DW-EPI pulse sequence is presented and then validated experimentally
      by measuring the diffusion tensor in an isotropic phantom whose diffusivity is
      already known. The b matrix is written in a convenient tabular form as a sum of
      individual pair-wise contributions arising from gradient pulses applied along
      parallel and perpendicular directions. While the contributions from readout and
      phase-encode gradient pulse trains are predicted to have a negligible effect on
      the echo, the contributions from other imaging and diffusion gradient pulses
      applied in both parallel and orthogonal directions are shown to be significant in
      our sequence. In general, one must understand and account for the multiplicity of
      interactions between gradient pulses and the echo signal to ensure that diffusion
      tensor imaging is quantitative.

PMID- 9001154
TI  - Improved 2D time-of-flight angiography using a radial-line k-space acquisition.
AB  - For flow imaging applications, radial-line k-space acquisition methods offer
      advantages over conventional 2DFT methods. Specifically, radial-line acquisition
      methods mitigate artifacts resulting from pulsatile flow while offering a
      potential reduction in scan times. In this paper, radial-line and 2DFT
      acquisitions are compared in a two-dimensional time-of-flight angiography
      sequence. The twisting radial-line (TwiRL) trajectory, a variant of 2D projection
      reconstruction, is used to represent the family of radial-line trajectories. In
      both phantom and in vivo studies, the TwiRL images demonstrate improved vessel
      depiction including a more uniform signal intensity and better delineation of the
      vasculature in comparison with images obtained via the 2DFT method.

PMID- 9001151
TI  - Angiographic imaging with 2D RF pulses.
AB  - Magnetic resonance angiography (MRA) was performed by using RF pulses designed to
      excite a limited spatial extent in two orthogonal directions. The restriction in
      the second spatial dimension can be used to increase inflow enhancement and to
      improve small field-of-view imaging. A rectangular excitation was produced with
      an "echo-planar" k-space trajectory and a sinc-modulated RF waveform. In vivo
      images have demonstrated that vessels are more clearly delineated with the two
      dimensional excitation. Aliasing artifacts in small field-of-view imaging are
      significantly reduced, although in some cases complete elimination is not
      possible due to the nature of the gradient trajectory.

PMID- 9001156
TI  - In vivo phosphorus polarization transfer and decoupling from protons in three
      dimensional localized nuclear magnetic resonance spectroscopy of human brain.
AB  - Refocused insensitive nucleus enhancement by polarization transfer (RINEPT) from
      protons (1H) to a J-coupled phosphorus (31P) has been incorporated into three
      dimensional (3D) chemical-shift-imaging (CSI) sequence on a clinical imager. The
      technique is demonstrated on a phantom and in in vivo human brain. The
      polarization-transfer efficiency (approximately 1.2) is lower than the
      theoretical maximum of gamma1H/gamma31P approximately 2.4 resulting from 1H-1H
      homonuclear J couplings of similar magnitude competing with the 1H --> 31P
      transfer. Nevertheless, compared with direct 31P Ernst-angle excitation, signal
      gains of up to x1.8 were obtained mainly as a result of T1 differences between
      31P and the 1H. Spectral interpretation is simplified by editing out all non
      proton-coupled 31P signals. The duration, approximately 50 min, and power
      deposition, approximately 1 W x kg(-1), make the application suitable for human
      studies.

PMID- 9001157
TI  - Application of a 3D volume 19F MR imaging protocol for mapping oxygen tension
      (pO2) in perfluorocarbons at low field.
AB  - A limited flip angle gradient-echo 3D volume acquisition imaging protocol for
      mapping partial pressure of oxygen (pO2) in perfluorocarbon compounds (PFCs) at
      low field (0.14 T) is presented. The PO2 measurement method is based on the
      paramagnetic effect of dissolved molecular oxygen (O2) which reduces the PFC 19F
      T1. Specific objectives related to imaging of PFCs through use of the protocol
      include improved image signal-to-noise characteristics and elimination of 19F
      chemical shift artifacts. A parametric Wiener deconvolution filtering algorithm
      is used for suppression of 19F chemical shift artifacts. Application of the
      protocol is illustrated in a series of calculated PO2 maps of a gas equilibrated,
      multi-chamber phantom containing perfluorotributylamine (FC-43). The utility of
      the protocol is demonstrated in vivo through images of a commercially available
      perfluorocarbon based blood substitute emulsion containing FC-43 sequestered in
      the liver and spleen of a rat.

PMID- 9001158
TI  - Polyvinyl alcohol cryogel: an ideal phantom material for MR studies of arterial
      flow and elasticity.
AB  - The authors present a unique application of polyvinyl alcohol (PVA) cryogel as an
      anthropomorphic, elastic, vascular phantom material that can be used in MR
      imaging. The composition consists of two nontoxic ingredients: water and PVA. The
      biomechanical and MR properties can be adjusted to be similar to those of excised
      porcine aortas by varying the number of freeze-thaw cycles to which the PVA
      solution is exposed. The authors present the T1, T2, shrinkage, and tensile
      properties of PVA cryogel tubes as a function of freeze-thaw cycles. MR images of
      a dual elastic aortic phantom undergoing pulsatile motion are shown.

PMID- 9001159
TI  - Introduction: management of osteoporosis, 1997.

PMID- 9001160
TI  - Estrogen therapy and osteoporosis: principles & practice.
AB  - Postmenopausal osteoporosis is linked clearly to estrogen deprivation. Recent
      research has identified estrogen receptors in bone cells and in other organ
      systems that help to regulate bone remodeling and calcium homeostasis. Long-term
      use of estrogen in appropriate doses reduces the risk of hip fractures by 50% to
      60% and the risk of vertebral deformation by 90%. This protective effect is
      maintained as long as estrogen is taken and adequate levels of biologically
      active estrogen are achieved. Thus, the type, dose, and route of administration
      of estrogen need to be individualized and the efficacy of treatment monitored by
      annual bone density testing and selective ultilization of biochemical bone
      markers. The ability of estrogen therapy to increase bone mass is enhanced by
      added androgens and progestin therapy, calcium supplementation, and exercise.

PMID- 9001161
TI  - Calcitonin.
AB  - Nasal calcitonin is a newly approved treatment for established osteoporosis.
      Nasal calcitonin is safe, preventative, and may increase bone mass in the lumbar
      spine. Fracture efficacy data are not yet available, although preliminary results
      are promising. The dose of nasal calcitonin for the treatment of established
      osteoporosis is 200 IU daily. The dose for prevention of postmenopausal
      osteoporosis has not yet been established. Nasal calcitonin may be analgesic to
      bone and of benefit in glucocorticoid-induced osteoporosis.

PMID- 9001162
TI  - Bisphosphonate therapy.
AB  - The bisphosphonates are long-lived synthetic analogs of pyrophosphate, a natural,
      short-lived inhibitor of bone. Oral doses share similar qualities (ie, they
      inhibit bone resorption, poor absorption, and potential gastrointestinal
      irritants), but each one has a unique spectrum of potency and a probable
      mechanism of action. The parent compound, etidronate, was first used in
      multicentered trials for the treatment of primary osteoporosis and showed some
      success in increasing bone density and perhaps controlling fracture rates. The
      recently approved drug alendronate is a more potent agent than etidronate,
      produces a greater increase in bone density, and decreases fractures. Oral and
      intravenous pamidronate have similar positive effects on bone density. Studies
      with tiludronate, risedronate, and clodronate show similar promise as therapeutic
      agents.

PMID- 9001163
TI  - Sustained-release sodium fluoride in the management of established postmenopausal
      osteoporosis.

PMID- 9001164
TI  - Miscellaneous and experimental agents.
AB  - Current therapeutic approaches to postmenopausal bone loss or established
      osteoporosis vary widely among the different regions of the world. Because no
      treatment of osteoporosis has unequivocally demonstrated full prevention of the
      appearance or the recurrence of axial or peripheral fractures so far, many
      investigational compounds are being developed. Anabolic steroids act mainly as
      inhibitors of bone resorption with very few, if any, effects on bone formation.
      Because of the high occurrence of signs of virilization and the weak effects on
      bone structure, the risk/benefit ratio in osteoporosis should be considered at
      least problematic. If ongoing large-scale trials confirm the expected benefits of
      estrogen antagonist/agonists on the skeleton and confirm no cardiovascular risk
      to postmenopausal women with optimal uterine safety, these substances are likely
      to become the most prominent alternative to hormonal replacement therapy after
      the menopause. Additional studies are requested to evaluate the potential benefit
      of growth hormone or insulin-like growth factors in treatment of osteoporosis.
      Ipriflavone acts predominantly as an inhibitor of bone resorption. To confirm the
      efficacy of ipriflavone on the prevention of vertebral fractures and its effects
      on bone mineral density in women with postmenopausal established osteoporosis, a
      large multicentric European study is being conducted. Treatment with parathyroid
      peptides induces a significant gain in bone mass, mainly in the axial skeleton.
      Long-term studies that compare peptides, doses, and regimes are needed to better
      understand the exact position of parathyroid peptides as treatment of
      osteoporosis. Prolonged administration of strontium to postmenopausal
      osteoporotic women resulted in a decoupling between bone resorption and formation
      that yielded a significant increase in the lumbar spine bone mineral density of
      treated subjects. In the view of these promising results and of the excellent
      tolerance of strontium during preliminary trials, additional investigations of
      this compound in prevention and treatment of osteoporosis should be promptly
      initiated. Several other compounds have been punctually suggested for treatment
      of osteoporosis or are at very early stages of development. Finally, besides
      pharmacologic approaches to the treatment of osteoporosis, hip fractures may also
      be reduced by the use of hip protectors.

PMID- 9001165
TI  - Corticosteroid-induced osteoporosis.
AB  - The pathophysiology of corticosteroid-induced osteoporosis is outlined in this
      article. Treatment options, based upon our understanding of the pathophysiology,
      and a review of the available literature are offered.

PMID- 9001166
TI  - Bacteremia in young urban women admitted with pyelonephritis.
AB  - The objective of this study was to determine the rate of bacteremia in young
      women admitted to the hospital with presumed pyelonephritis and compare it with
      other published rates. The study design was a retrospective, structured chart
      review and a review of published reports of bacteremic pyelonephritis. An urban
      county teaching hospital provided the setting for the study. The patients were
      nonpregnant women (n = 98) 44 years of age or younger who were without bladder
      dysfunction and who had not been admitted to an intensive care unit. Further
      criteria for participation included discharge with the diagnosis of acute
      pyelonephritis. Blood cultures were ordered for 69 women; the results of 64 were
      noted in the chart. Twenty-three women (35.9% of those cultured; 23.4% of all
      patients) were diagnosed with bacteremia. In patients for whom blood culture
      results were obtained, trends developed between those patients with bacteremia
      and those with complicated pyelonephritis, defined as a known or newly discovered
      genitourinary abnormality or a risk factor (P = 0.044), those who were black (P =
      .044), those with higher pulses on admission (P = .050), those with more white
      blood cells per high-powered field after urinalysis (P = 0.007), and those whose
      fever lasted longer (P = 0.033). Blood culture results were positive in two
      patients whose urine cultures were negative. This comparatively high bacteremia
      rate supports routine ordering of blood cultures for urban women suspected of
      having pyelonephritis.

PMID- 9001167
TI  - Case records of the Medical College of Virginia, Virginia Commonwealth University
      Clinicopathologic Conference. A 27-year-old man with hematuria.

PMID- 9001168
TI  - Insulin-dependent diabetes mellitus associated with autoimmune thyroiditis and
      rheumatoid arthritis.
AB  - A case associated with insulin-dependent diabetes mellitus (IDDM), rheumatoid
      arthritis (RA), and autoimmune thyroid disease (AITD) was reported. A high titer
      of anti-glutamic acid decarboxylase antibody (GAD) and a positive islet cell
      antigen were observed. The patient's human leukocyte antibody (HLA) haplotype was
      a homozygote of DQA1*0301, DQB1*0401, and DRB1*0405. Because this haplotype was
      in linkage disequilibrium with DPB1*0501, an allele associated with AITD in
      Japanese patients, the patient was homozygous for alleles susceptible to IDDM,
      RA, and AITD. A specific HLA haplotype susceptible to several autoimmune disease
      may result in the development of IDDM, RA, and AITD.

PMID- 9001169
TI  - Alopecia universalis with remission during pregnancy and prednisolone therapy.
AB  - In a 32-year-old woman, alopecia universalis went into unequivocal remission
      during pregnancy and prednisolone therapy. A skin biopsy specimen showed intense
      infiltration of the lymphocyte around the hair follicle without immunoglobulin
      and complement deposition. Autoantibody test results were negative except for the
      antithyroid and anti-nuclear antibodies. Human leukocyte antigen haplotypes
      common in Japanese patients with insulin-dependent diabetes were found in this
      patient. However, thyroid function and glucose tolerance were normal, and other
      clinical evidence of collagen vascular disorders was not found. In this patient,
      alopecia was considered to have been caused by autoimmune abnormalities. This is
      the first documentation of remission of autoimmune alopecia universalis during
      pregnancy.

PMID- 9001170
TI  - Gastrointestinal involvement in neurologic disorders: Stiff-man and Charcot-Marie
      Tooth syndromes.
AB  - Many neurologic conditions can affect the striated muscle of the gastrointestinal
      tract, resulting in dysphagia. In this article, two patients with rare neurologic
      disorders are reported (Stiff-man syndrome and Charcot-Marie-Tooth syndrome).
      Both patients had pharyngeal dysphagia. In addition, there was evidence of smooth
      muscle involvement in other areas of the gastrointestinal tract, specifically
      abnormal esophageal motility and delayed gastric emptying. In the English
      literature, there are only two reports of Stiff-man syndrome and dysphagia, and
      there are no reports of Charcot-Marie-Tooth syndrome. These represent the first
      accounts of smooth muscle dysfunction in those uncommon neurologic disorders.

PMID- 9001171
TI  - Mousepox outbreak in a laboratory mouse colony.
AB  - Mousepox was diagnosed in and eradicated from a laboratory mouse colony at the
      Naval Medical Research Institute. The outbreak began with increased mortality in
      a single room; subsequently, small numbers of animals in separate cages in other
      rooms were involved. Signs of disease were often mild, and overall mortality was
      low; BALB/cByJ mice were more severely affected, and many of them died
      spontaneously. Conjunctivitis was the most common clinical sign of disease in
      addition to occasional small, crusty scabs on sparsely haired or hairless areas
      of skin. Necropsy findings included conjunctivitis, enlarged spleen, and pale
      liver. Hemorrhage into the pyloric region of the stomach and proximal portion of
      the small intestine was observed in experimentally infected animals. In immune
      competent and immune deficient mice, the most common histologic finding was
      multifocal to coalescing splenic necrosis; necrosis was seen less frequently in
      liver, lymph nodes, and Peyer's patches. Necrosis was rarely observed in ovary,
      vagina, uterus, colon, or lung. Splenic necrosis often involved over 50% of the
      examined tissue, including white and red pulp. Hepatic necrosis was evident as
      either large, well-demarcated areas of coagulative necrosis or as multiple,
      random, interlacing bands of necrosis. Intracytoplasmic eosinophilic inclusion
      bodies were seen in conjunctival mucosae and haired palpebra. Ectromelia virus
      was confirmed as the causative agent of the epizootic by electron microscopy,
      immunohistochemistry, animal inoculations, serologic testing, virus isolation,
      and polymerase chain reaction. Serologic testing was of little value in the
      initial stages of the outbreak, although 6 weeks later, orthopoxvirus-specific
      antibody was detected in colony mice by indirect fluorescent antibody and enzyme
      linked immunosorbent assay procedures. The outbreak originated from injection of
      mice with a contaminated, commercially produced, pooled mouse serum. The most
      relevant concern may be the unknown location of the source of the virus and the
      presence of a reservoir for this virus within the United States.

PMID- 9001172
TI  - Increased survival of CFTR knockout mice with an oral osmotic laxative.
AB  - Mouse models of cystic fibrosis that are generated by targeted disruption
      (knockout) of the cystic fibrosis transmembrane conductance regulator gene, cftr(
      /-), typically die shortly after weaning, from intestinal obstruction/rupture
      caused by an inability to secrete fluid into the bowel lumen. We investigated the
      use of a commercial osmotic laxative, Colyte, provided continuously in the
      drinking water, to increase the survival of cftr(-/-) mice. Genotype analysis of
      623 offspring surviving at 10 days of age yielded 28.1% cftr(+/+), 59.6% cftr(+/
      ), and 12.4% cftr(-/-) mice (25% predicted), suggesting that cftr(-/-) mice have
      a significant perinatal mortality rate. However, of the 77 cftr(-/-) mice alive
      at 10 days of age, >98% survived weaning and were maintained in apparent health
      to a minimum of 56 days of age (arbitrary age for experimentation). In intestinal
      bioelectric studies Colyte-treated drinking water, compared with tap water, had
      no significant effect on basal short-circuit current, cyclic AMP-stimulated Cl-
      secretion, Na+-coupled glucose absorption, or electrogenic Na+ absorption across
      intestinal sections from cftr(+/+ or +/-) mice. Other than a mild dilatation of
      the distal portion of the colon in the Colyte-treated animals, examination of
      jejunal and colonic sections revealed no histologic differences between the two
      treatments. These findings indicate that the chronic use of Colyte osmotic
      laxative in drinking water is an economical means of greatly increasing the
      survival of CFTR knockout mice without altering the major electrolyte transport
      processes or histomorphologic integrity of the intestine.

PMID- 9001174
TI  - Proliferative enteropathy of rabbits: the intracellular Campylobacter-like
      organism is closely related to Lawsonia intracellularis.
AB  - The intracellular Campylobacter-like organism associated with proliferative
      enteropathy of rabbits is closely related to Lawsonia intracellularis, the
      primary pathogen in porcine intestinal adenomatosis. Polymerase chain reaction
      primers based on the 16S rRNA gene of L. intracellularis were used to amplify DNA
      harvested from intestinal tissues of rabbits with severe proliferative intestinal
      lesions containing curved argentophilic intracellular bacteria. Sequencing of a
      180-nucleotide DNA fragment of the 550-base pair-amplified polymerase chain
      reaction product revealed >98% similarity between the organism associated with
      the rabbit disease and the homologous sequence found in L.intracellularis.

PMID- 9001173
TI  - Increased enzyme-linked immunosorbent assay specificity with solubilized simian
      retrovirus 2-infected cell membranes.
AB  - Simian type-D retrovirus (SRV) infection is a health problem in captive and wild
      caught macaques; it interferes with acquired immune deficiency syndrome-related
      research. Because the enzyme-linked immunosorbent assay (ELISA) with gradient
      purified SRV-2 virus yields a high percentage of false-positive results, the
      assay was modified with membrane antigens from SRV-2-infected and uninfected A549
      cells. The SRV-2 membrane antigen contains the major proteins detected in
      positive sera by Western blotting: env proteins gp70 and gp20 and gag proteins
      p27, p14, p12, and p10. The original purified virus ELISA had a specificity of
      74% compared with Western immunoblot. The modified ELISA using the difference in
      optical density between infected and control cell membrane antigens resulted in a
      specificity of 100% when the same samples were tested.

PMID- 9001176
TI  - High prevalence of gastric trichobezoars (hair balls) in Wistar-Kyoto rats fed a
      semi-purified diet.
AB  - Gastric trichobezoars (hair balls) are frequently found in rabbits but are rarely
      reported in rats. Several Wistar-Kyoto rats fed a semi-purified diet developed
      anorexia and abdominal tenderness. Proteolysis therapy with fresh papaya and
      commercially prepared enzyme was attempted in these rats but was not successful.
      The prevalence of trichobezoars at necropsy was 100%. We conclude that semi
      purified diets contribute to trichobezoar formation in rats, but proteolysis
      therapy is not effective in dissolving the trichobezoars.

PMID- 9001175
TI  - Detection of Pneumocystis carinii in rats by polymerase chain reaction:
      comparison of lung tissue and bronchoalveolar lavage specimens.
AB  - The purpose of this study was to determine and compare the efficiency of
      detection of Pneumocystis carinii in rats by polymerase chain reaction (PCR) of
      DNA extracted from two sampling locations: lung tissue and bronchoalveolar
      lavage. The study involved naturally infected F344 rats that were allotted to
      groups to intercollate the investigation of several variables, including
      nonimmunosuppressed rats, rats subjected to a timed induction sequence of 1 to 4
      weeks of immunosuppression, and two immunosuppressants: a corticosteroid and
      cyclophosphamide. The PCR amplified a 357-base pair region contained within the
      gene encoding the large ribosomal RNA subunit of P. carinii mitochondrial DNA.
      The identity of the PCR product was confirmed by Southern blot analysis with an
      oligonucleotide probe. In a comparison of lung bronchoalveolar lavage specimens
      after immunosuppression, P. carinii was detected by PCR in 100% of lung tissue
      but in only 87.5% of the lavage specimens. Lung tissue of three animals was test
      positive when the corresponding lavage specimen was negative by PCR analysis. The
      PCR detected P. carinii in both types of specimens from the same two of three
      nonimmunosuppressed rats. In all there was 88% agreement of PCR results between
      the two sampling techniques. The difference in diagnostic outcome for the two
      specimen types was not statistically significant (Fisher's exact test). It was
      concluded that both specimen types were adequate for PCR detection of P. carinii
      in rats.

PMID- 9001177
TI  - Beagle model used in a tissue tolerance study of the response of normal and
      surgically manipulated liver to single high-dose intraoperative radiotherapy.
AB  - To investigate the feasibility of delivering a single large dose of
      intraoperative electron beam radiotherapy (IORT) to the liver of clinically
      normal and partially hepatectomized beagles, an experimental study was designed.
      The purpose of the study was to obtain dose guidelines for the delivery of IORT
      to the liver of human patients with colorectal cancer metastases to the liver.
      After partial resection of the liver, IORT in doses up to 30 Gy was applied to
      the resection plane as well as to a nonsurgically manipulated part of the liver
      of 25 beagles. The temporal sequence of histologic changes of these irradiated
      parts of the liver tissue was investigated. There were no postoperative
      complications and no morbidity or mortality associated with a minimal follow-up
      of 3 years. Necropsy performed 3 months after IORT revealed only mild
      histopathologic changes. One year after IORT, more distinct histopathologic
      changes consisting of capsular thickening, diffuse parenchymal fibrosis, and
      subcapsular hepatocellular atrophy were found. Three years after IORT, the
      parenchymal architecture seemed to be restored, although loss of liver tissue was
      definitive at the irradiation site; liver function remained intact. These results
      indicate that IORT to part of the liver in the canine model can be safely applied
      and that, although doses up to 30 Gy can result in severe local tissue damage,
      wound healing and liver function are not disturbed.

PMID- 9001178
TI  - A model for the extended studies of hepatic hemodynamics and metabolism in swine.
AB  - To our knowledge postoperative hepatic hemodynamics and hepatic metabolism have
      not been fully studied on a long-term basis. Our goal was to develop a large
      animal model that would permit the measurement of hepatic blood flow (BF),
      perihepatic pressures (P), and hepatic metabolism in a long-term setting.
      Catheters were inserted into the jugular vein, carotid artery, pulmonary artery,
      hepatic vein, and portal vein (PV) of 27 commercially bred pigs; ultrasonic
      transit time flowmeter probes were placed around the hepatic artery and PV. Daily
      postoperative measurements of jugular vein P, carotid artery P, pulmonary artery
      P, hepatic vein P, and PVP, as well as hepatic artery BF and PVBF, were recorded
      for 20 days. Hepatic carbohydrate metabolism was assessed by arteriovenous
      difference techniques. Jugular vein P, pulmonary artery P, hepatic vein P, PVP,
      and heart rate reached steady-state values during the first week, with a mean +/-
      SEM of 1.0 +/- 0.3 mm Hg for jugular vein P, 21.4 +/- 2.1 mm Hg for pulmonary
      artery P, 4.3 +/- 0.4 mm Hg for HVP, 7.8 +/- 0.5 mm Hg for PVP, and 116 +/- 4
      beats per minute for heart rate. Mean carotid artery P increased from 65 +/- 3 mm
      Hg during surgery to 94 +/- 2 mm Hg on postoperative day 1 (P < 0.001) and to a
      mean 101 +/- 2 mm Hg thereafter. Total hepatic BF reached a steady-state value of
      1,132 +/- 187 ml/min by postoperative day 7 (P = 0.19). Over week 1 hepatic
      artery BF measured as a percentage of total hepatic BF decreased from 35.0 +/-
      3.0% to 15.5 +/- 2.7%, and PVBF increased from 65.0 +/- 3.0% to 84.5 +/- 2.7% (P
      < 0.005); both variables were steady thereafter. In the hemodynamic steady state
      the net hepatic balances of glucose, lactate, glycerol, and alanine in 5 pigs
      were 9.9 +/- 4.0, -4.2 +/- 0.4, -2.3 +/- 1.1, and -0.68 +/- 0.22 micromol/kg per
      min respectively. The net gut (portal-drained viscera) balances of glucose,
      lactate, alanine, and glycerol were -2.0 +/- 2.5, 1.1 +/- 0.5, 0.73 +/- 0.18, and
      -0.69 +/- 0.19 micromol/kg per min respectively. Thus, a reliable large animal
      model was developed to study acute and chronic hepatic hemodynamics and
      metabolism.

PMID- 9001179
TI  - Microbiologic, radiographic, and anatomic study of the nasolacrimal duct
      apparatus in the rabbit (Oryctolagus cuniculus).
AB  - This study was motivated by the sporadic observation of epiphora in two male
      rabbits. The epiphora was unilateral and not associated with conjunctivitis or
      Pasteurella infection. To characterize the cause of epiphora, we studied 15
      specific-pathogen-free New Zealand White rabbits. This study group was composed
      of the two affected males, four unaffected males, and nine unaffected females.
      Clinical evaluation consisted of bacterial culture of conjunctival specimens,
      examination of conjunctival scrapings for chlamydial inclusions, culture and
      cytologic examination of specimens from the nasolacrimal duct, plain and contrast
      radiography, latex casting, histologic examination, and the Schirmer tear test.
      Important differences found in the rabbits with epiphora included an opalescent,
      gritty, nasolacrimal duct flush fluid and marked unilateral dilatation of the
      duct proximal to a dorsal flexure at the caudal limit of the incisor tooth root.
      The flush solution from one affected rabbit cleared with ether, suggesting the
      presence of triglycerides or cholesterol. The organisms most commonly isolated
      from the conjunctiva were Moraxella sp., Oligella urethralis, Staphylococcus
      aureus, coagulase-negative Staphylococcus sp., and Streptococcus viridans. The
      organisms most commonly isolated from the nasolacrimal duct flush fluid were
      Moraxella sp., S. viridans, and Neisseria sp. Culture of the nasolacrimal duct
      flush fluid yielded microorganisms more consistently than did culture of the
      conjunctival specimens. All microorganisms isolated from affected rabbits also
      were isolated from unaffected rabbits. There was no apparent contribution of
      microorganisms to the development of epiphora, and Schirmer tear test results for
      affected animals were within the range seen in unaffected animals. Occlusion of
      the nasolacrimal duct was presumed to be attributable to fat droplets. This study
      augments the existing literature and represents the first report of anomalous
      nasolacrimal duct anatomic features in the rabbit.

PMID- 9001180
TI  - Timing of induced ovulation in C.B-17/Icr-scid/scid and B6SJLF1 mice.
AB  - The time of induced ovulation after superovulation was evaluated in 3- to 8-week
      old C.B-17/Icr-scid/scid and B6SJLF1 mice. Mice received intraperitoneal
      injections of 5 IU of equine chorionic gonadotropin (CG) followed by 5 IU of
      human (h) CG 48 h apart. Hormones were administered at 1700. Mice were kept on a
      14-h light cycle, with lights off at 1900. Nine mice of each strain were
      sacrificed (3 mice x 3 replicates) at 8, 10, 12, 14, and 16 h after hCG
      injection. Ovaries and oviducts from each mouse were removed and placed in M-2
      collection medium in one well of a 9-well Pyrex culture plate. The oviducts were
      flushed with M-2 medium, and the number of oocytes from each mouse was counted
      under a binocular Nikon dissecting microscope. Both mouse strains began ovulating
      at 8 h after hCG administration. Ovum counts peaked at 12 h in B6SJLF1 mice and
      at 16 h in C.B-17/Icr-scid/scid mice. A statistically significant strain
      difference between mean oocytes collected was detected at 10 and 12 h. For both
      time points, differences were at the 1% level of significance. There was no
      difference in the mean number of oocytes collected at 14 and 16 h. The mean
      number of ovulated oocytes increased markedly between 10 to 12 h after hCG in
      B6SJLF1 mice. The number of ovulated oocytes also increased in C.B-17/Icr
      scid/scid mice, although more gradually. These results suggest that the timing of
      ovulation may be more tightly controlled in superovulated B6SJLF1 than in C.B
      17/Icr-scid/scid mice. Superovulated C.B-17/Icr-scid/scid mice finish ovulation 2
      to 4 h later than do B6SJLF1 mice. Therefore the best time to harvest pronuclear
      embryos should be 14 to 16 h after hCG administration in C.B-17/Icr-scid/scid
      mice and 12 h after hCG in B6SJLF1 mice. To optimize fertilization, mating should
      occur within 3 h of ovulation and should be planned from 11 to 17 h after hCG for
      C.B-17/Icr-scid/scid mice and 9 to 15 h after hCG in B6SJLF1 mice. Because male
      and female pronuclei form 4 to 7 and 6 to 9 h respectively after insemination,
      the most pronuclear stage embryos should be obtained by collecting them 20 to 21
      h after hCG in C.B-17/Icr-scid/scid mice and 18 to 19 h in B6SJLF1 mice.

PMID- 9001181
TI  - Collection of seasonally spermatozoa-rich semen by electroejaculation of
      laboratory woodchucks (Marmota monax), with and without removal of bulbourethral
      glands.
AB  - Male woodchucks were subjected to electroejaculation during the early- or mid
      breeding season by a commercial stimulator and rectal probe (1.3 x 13 cm, with
      longitudinal electrode strips on one side) with electrodes oriented ventrally. A
      study of the voltage and stimulation parameters at a probe depth of 4 to 9 cm
      suggested that a series of 15 to 75 3-sec pulses of 3 to 6 V each could result in
      ejaculation and collection of semen. Pulses of only 1 to 2 V frequently caused
      erection but not ejaculation. Trials conducted on 12 bulbourethral (Cowper's)
      gland-intact males (n = 18 trials) versus six males from which Cowper's glands
      had been surgically removed (n = 18 trials) identified these glands as the source
      of urethral plugs in 77% of ejaculates from the gland-intact males and presumably
      the source of copulation plugs obtained from the vagina of female woodchucks. The
      fluid portion of ejaculates from both groups contained few or no spermatozoa. An
      additional 32 trials were conducted on 12 gland-intact males and eight males
      without Cowper's glands. These trials included 16 shallow (5 to 8 cm) versus 16
      deep (10 to 13 cm) placements of the tip of the rectal probe in each group of
      males. In gland-intact males the stimulation of sacral (shallow) elements
      routinely resulted in the emission of large (200 to 300 microl) urethral plugs
      and fluid volume of 40 to 400 microl, containing few or no spermatozoa. In males
      without Cowper's glands the sacral stimulation typically produced volumes of 60
      to 350 microl of noncoagulating liquid without urethral plugs, containing few or
      no spermatozoa. Lumbar (deep) stimulation in both groups of males usually
      resulted in fluid ejaculates, with 60% containing numerous spermatozoa
      (typically, 0.5 to 3 x 10(6)/ejaculate). Lumbar stimulation usually produced
      urethral plugs of little (50 to 100 microl) or no volume in gland-intact males
      and no urethral plugs in males without Cowper's glands. Ejaculates did not
      coagulate during handling or storage for 4 to 24 h. Serial lumbar stimulation of
      six males at 2- to 3-week intervals resulted in few spermatozoa, except for a 4-
      to 8-week period during which > or =0.25 x 10(6) spermatozoa/ejaculate and peaks
      of 5.3 +/- 2.4 x 10(6) spermatozoa/ejaculate were obtained. The results suggest
      that electroejaculation can be used to obtain spermatozoa-containing liquid that
      might be useful for semen evaluation or artificial insemination in laboratory
      woodchucks, that Cowper's glands are the source of urethral plugs in the
      ejaculates of this species, and that the fertile period of the male breeding
      season is limited to 4 to 8 weeks.

PMID- 9001182
TI  - Diagnostic exercise: parasitic organisms found in a South African clawed toad.

PMID- 9001183
TI  - Limited diversity in the major histocompatibility complex class II loci of Syrian
      hamster DNA.

PMID- 9001184
TI  - Zucker rat (fa/fa), a model for the study of immune function in type-II diabetes
      mellitus: effect of exercise and caloric restriction on the phagocytic activity
      of macrophages.

PMID- 9001185
TI  - Cryptosporidiosis in mice in Argentina.

PMID- 9001186
TI  - Transport of wild mice genetic material by in vitro fertilization,
      cryopreservation, and embryo transfer.

PMID- 9001187
TI  - Sustained estrogenization is insufficient to support long-term experimentally
      induced genital Trichomonas vaginalis infection in BALB/c mice.

PMID- 9001188
TI  - T-cell recognition of residue 158-176 in thyrotropin receptor confers risk for
      development of thyroid autoimmunity in siblings in a family with Graves' disease.
AB  - Twenty-two subjects in a family with Graves' Disease and 20 normal subjects
      unrelated to the family were examined for T-cell responses to rec h TSHR-ECD and
      its synthetic peptides. Seven of the family members and none of the controls
      responded positively to rec h TSHR-ECD. Peptide 158-176 was the only residue that
      showed a high percentage of response among family members, no responses in
      spouses, and a significant difference compared to unrelated controls. Family
      members under age of 6 did not differ from spouses in response to rec h TSHR-ECD
      or any individual peptide. Family members ages 6-12 years were significantly
      different from spouses in response to peptides 30-49, 158-176, and 172-186. The
      reactivity of adult family members including 3 Graves' patients was significantly
      different from spouses in response to peptides 44-62, 132-150, 158-176, and 248
      263. The responses of female members of the family were higher than that of the
      male members and significantly different for peptide 272-291. These data suggest
      that recognition of peptide 158-176 may be an early event in the pathogenesis of
      the disease and that recognition of both 158-176 and 248-263 residues may be the
      cornerstone for establishment of the disease.

PMID- 9001189
TI  - Localization and clinical significance of thyrotropin receptor mRNA expression in
      orbital fat and eye muscle tissues from patients with thyroid-associated
      ophthalmopathy.
AB  - We have studied the cellular localization of thyrotropin receptor (TSH-R) mRNA in
      orbital fat and extraocular muscle tissues from patients with thyroid-associated
      ophthalmopathy (TAO) using Northern blot, reverse transcriptase polymerase chain
      reaction (RT-PCR), and in situ hybridization, and we correlated the findings with
      clinical estimates of ophthalmopathy. Although we failed to detect TSH-R mRNA in
      orbital tissues by Northern blot, TSH-R cDNA was amplified in orbital fat tissue
      from 13 of 25 patients with TAO and from 2 of 4 control subjects, in eye muscle
      tissue from 2 out of 7 patients with TAO, and in cultured orbital fibroblasts and
      subcutaneous fibroblasts from TAO patients. In situ hybridization showed that TSH
      R mRNA was detected in cultured orbital fibroblasts as well as skin fibroblasts
      obtained from the patient. Furthermore, the expression of TSH-R mRNA in orbital
      fat tissue from patients with TAO significantly correlated with the orbital fat
      volume and the severity of ophthalmopathy, especially the extent of eye muscle
      dysfunction. These results suggest that the expression of TSH-R in the orbit,
      especially fibroblasts, may play a role in the pathogenesis and clinical
      manifestations of the ophthalmopathy in patients with TAO, although a secondary
      effect, involving fibroblasts in TAO is also possible.

PMID- 9001190
TI  - Differences in response of thyrotropin to 3,5,3'-triiodothyronine and 3,5,3'
      triiodothyroacetic acid in patients with resistance to thyroid hormone.
AB  - This study investigated the response of TSH secretion to 3,5,3'-triiodothyronine
      (T3) and 3,5,3'-triiodothyroacetic acid (Triac) in patients with resistance to
      thyroid hormone, and compared the responses with those in patients with TSH
      secreting pituitary adenoma and normal subjects. A short-term administration of
      75 microg of T3 daily for 7 days suppressed serum TSH concentrations almost
      completely in normal subjects, but suppressed TSH only partially in patients with
      resistance to thyroid hormone and TSH-secreting pituitary adenoma. A single-dose
      administration of 75 microg of T3 gave similar results in regard to TSH
      suppressibility in these three subjects groups. In contrast, a single-dose
      administration of 1.4 mg of Triac remarkably suppressed serum TSH concentrations
      after 2 hours in not only normal subjects (-34 +/- 11% [mean +/- SD] from the
      basal value) but also in patients with resistance to thyroid hormone (-31 +/-
      9%), and this TSH suppression continued for 4 hours. After 24 hours, this TSH
      suppression persisted in normal subjects (-62 +/- 12%) but was relieved in
      patients with resistance to thyroid hormone (-23 +/- 14%). After the Triac
      administration, molar ratios of alpha-subunit to TSH in serum were decreased in
      patients with TSH-secreting pituitary adenoma but increased in patients with
      resistance to thyroid hormone. Because the Triac therapy for patients with
      resistance to thyroid hormone suppressed pituitary-TSH secretion during the early
      phase of drug ingestion, this drug should be given several times within a day to
      obtain continuous TSH-suppressive effects.

PMID- 9001191
TI  - Mutation in the thyroid hormone receptor (TR) beta gene (M313T) not previously
      reported in two unrelated families with resistance to thyroid hormone (RTH).
AB  - Two families expressing the RTH phenotype and harboring the same mutation in the
      TRbeta gene are described. Five and four affected members in each family were
      investigated as well as a total of 12 unaffected relatives. The mutation, a T to
      C transition of nucleotide 1223 in one allele of affected individuals, results in
      the replacement of the normal Met for a Thr. Haplotyping revealed that the same
      mutation developed in each family independently. Whereas attention deficit
      hyperactivity disorder was associated with RTH in 7 of the 9 affected
      individuals, it was also present in 2 family members without RTH.

PMID- 9001192
TI  - TSH-receptor expression and human thyroid disease: relation to clinical,
      endocrine, and molecular thyroid parameters.
AB  - Thyrotropin receptor (TSH-R) gene expression can be positively or negatively
      regulated by TSH and stimulating TSH-R antibodies (TSAbs) in immortalized thyroid
      cell lines such as rat FRTL-5 cells. However, regulation is less clear in other
      mammalian cells including cultures of human thyroid cells. Additionally, it has
      been suggested, based on FRTL-5 cell data, that TSH-R gene negative regulation by
      TSH or TSAbs might be lost in Graves' disease. The present study evaluated TSH-R
      gene transcript levels in thyroids from patients with Graves' disease to
      correlate in vivo data with in vitro observations or hypotheses. TSH-R mRNA
      levels were characterized in a total of 66 human thyroid glands with particular
      concern to levels in Graves' patients. Results were related to clinical
      parameters, transcript levels of thyroglobulin (TG), and thyroid peroxidase
      (TPO), as well as transcript levels of thyroid transcription factor 1 (TTF-1)
      which regulates the expression of all three genes and paired box-gene 8 (Pax-8)
      which regulates TG and TPO gene expression. Northern blot analyses showed that
      TSH-R expression was significantly increased, 2.2-fold, in Graves' thyroids (p =
      0.0098, n = 35) by comparison to normals (n = 6). TSH-R mRNA levels were
      decreased to 30% and 7% of normal levels in Hashimoto's thyroids (p = 0.0281, n =
      5) and anaplastic carcinomas (p = 0.0033, n = 6), respectively. No significant
      changes were seen in endemic goiters (n = 8) and in thyroid autonomy (n = 6). TSH
      R RNA levels were higher, 3.6-fold, in thyroids of a subgroup of Graves' patients
      that had not been pretreated with iodide before surgery (n = 10) by comparison to
      thyroids from those that had been treated before surgery, 1.7-fold (n = 25). TSH
      R antibodies exhibited a nonsignificant tendency toward a negative correlation.
      All other clinical or endocrine parameters showed no clear relation to TSH-R mRNA
      levels. Pax-8 and TTF-1 transcripts were detectable in normal thyroids; however,
      Pax-8 expression was increased in Graves' thyroids (3.8-fold), whereas TTF-1
      expression was only minimally changed in all thyroids investigated. Changes of
      the two did not correlate. Pax-8 expression correlated with TG and TPO expression
      (in all cases, p = 0.0001); TTF-1, despite its minimal change, still correlated
      with TG (p = 0.0471) but not with TPO expression (p = 0.0984). TTF-1, again
      despite its minimal changes, correlated positively with TSH-R gene expression (p
      = 0.0251); however, surprisingly, Pax-8, which does not regulate TSH-R gene
      expression, correlated even better with TSH-R transcript levels (p = 0.0001). We
      conclude that augmentation of TSH-R expression levels, and thus potential ligand
      binding sites, may indicate an important regulatory principle in the pathogenesis
      of autoimmune hyperthyroidism in vivo: the responsiveness of the TSH-R to TSH and
      TSAb induced negative regulation is lost. This increase of TSH-R expression
      levels is not due to an ongoing transcriptional activation of the TTF-1 gene. Pax
      8, though positively correlated with TSH-R RNA levels, cannot be the factor
      either, because Pax-8 does not upregulate TSH-R expression. This predicts that
      other factors involved in TSH-R induced negative regulation are abnormal and must
      be searched for and evaluated.

PMID- 9001193
TI  - Evaluation of pituitary and peripheral tissue markers of thyroid hormone action
      in an Iranian family with resistance to thyroid hormone.
AB  - Resistance to thyroid hormone (RTH), an inherited syndrome of reduced sensitivity
      to thyroid hormone, is being detected with increased frequency. We report the
      first family with RTH identified in Iran. Goiter prompted thyroid evaluation, and
      nonsuppressed TSH associated with high free T4, suggested RTH as the etiology.
      The mother and all four of her children expressed the RTH phenotype associated
      with attention deficit and hyperactivity. Detailed clinical and laboratory
      studies before and following the administration of graded doses of L-T3
      demonstrated relatively severe resistance to the hormone at the level of the
      thyrotrophs and peripheral tissues. Our data underscore the importance of
      evaluating the changes of various parameters of thyroid hormone action in
      response to thyroid hormone rather than their measurement at baseline or
      assessment of absolute levels.

PMID- 9001194
TI  - Altered thyroid hormone binding to plasma lipoproteins in hypothyroidism.
AB  - Iodothyronine binding to plasma lipoproteins (Lp) and gel filtration elution
      patterns of cholesterol and triglycerides were evaluated in the total lipoprotein
      fractions (TLF) obtained from 10 healthy blood donors and 7 patients with
      hypothyroidism of brief duration. TLF (d < 1.210 kg/L) shown to be free of plasma
      T4 transport proteins (TBG, TTR, HSA) was equilibrated with 0.3 nM 125I-labeled
      T4, T3 or reverse T3 (rT3) and chromatographed on Sepharose CL-6B. Percent
      distribution of rT3 among the Lp subtypes was similar in the two groups (in
      normals: VLDL = 4.2 +/- 2.4, LDL = 15.6 +/- 4.2, HDL = 79.9 +/- 5.2) but HDL in
      hypothyroid subjects bound significantly more T4 (98.7 +/- 0.4 vs. 91.2 +/- 0.3%)
      and T3 (95.5 +/- 2.6 vs. 78.3 +/- 11.3%). Correspondingly less T4 and T3 was
      bound to VLDL and LDL. Whereas rT3 elution coincided with the major HDL
      cholesterol peak (202 +/- 17 kDa) and was the same in the two groups, both T4 and
      T3 eluted with smaller HDL particles and differed between hypothyroid and normal
      subjects. T4 eluted with somewhat larger HDL particles in hypothyroid subjects
      (176 +/- 24 kDa vs. 111 +/- 34 kDa) and T3 eluted with smaller HDL (94 +/- 30 kDa
      vs. 148 +/- 31 kDa). The major HDL-cholesterol peak in hypothyroid subjects had a
      slightly but significantly greater mass than in normals (241 +/- 28 kDa vs. 218
      +/- 14 kDa). The HDL elution patterns also differed: in normals there were from 3
      to 6 minor peaks on either side of the major peak, whereas in hypothyroid
      subjects there were only 0 to 2 minor peaks. In conclusion, iodothyronines bind
      to relatively small size HDL subfractions and these are different for T4, T3, and
      rT3; hypothyroidism of brief duration induces both quantitative and qualitative
      changes in iodothyronine distribution among lipoproteins and alters the
      microheterogeneity of HDL-cholesterol.

PMID- 9001195
TI  - Elevated serum interleukin-6 and decreased thyroid hormone levels in
      postoperative patients and effects of IL-6 on thyroid cell function in vitro.
AB  - We studied a wide variety of surgical patients to determine whether serum levels
      of interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) correlate with
      the changes in serum thyroid hormone levels of the postoperative period. Surgical
      procedures were divided into minor surgery (cholecystectomy, n = 12), moderate
      surgery (colorectal cancer and stomach cancer, n = 54), and extensive surgery
      (esophageal cancer or pancreatic cancer, n = 6). One day after surgery, serum
      free T3 levels decreased in all 3 groups when compared to the preoperative
      values; serum free T4 levels did not change regardless of surgical procedure.
      Serum TSH levels decreased significantly 1 day after surgery in the groups of
      moderate and extensive surgery. Serum levels of IL-6 increased 12 h after surgery
      and began to decrease gradually thereafter. There was no change in serum levels
      of TNF-alpha before and after surgery. The increment of serum IL-6 was dependent
      on the surgical procedures: the more extensive the surgery, the greater the
      increase in serum IL-6. Serum free T3 and free T4 levels were inversely
      correlated with the serum levels of IL-6. To further examine whether IL-6 is
      responsible for alteration of thyroid hormone production, cultured porcine
      thyroid follicles were exposed to 0 to 20 ng/ml of recombinant human IL-6 for 24
      to 48 h. Then, type 1 5'-deiodinase activity (T4 to T3 converting enzyme), iodide
      uptake, and thyroid peroxidase (TPO) activity were measured. Our in vitro
      experiments showed no effect of IL-6 on these parameters. In summary, surgical
      procedure can cause elevation of serum IL-6 and decrease in serum free T3 levels.
      However, IL-6 alone does not appear to be a strong candidate for alteration of
      thyroid hormone production including T3 generation from T4.

PMID- 9001196
TI  - Metastasis to the liver in well-differentiated carcinoma of the thyroid.
AB  - Eleven patients (6 women; 5 men) of a series of 1,916 developed liver metastasis
      from differentiated thyroid cancer within 3 months to 202 months after the
      initial diagnosis. Liver metastasis generally appeared after the onset of
      metastases at other sites. The metastasis to the liver was clinically suspected
      in 8 patients whereas it was accidentally diagnosed on ultrasound examination of
      abdomen for a complaint of back pain in 1 patient, on a whole body diagnostic
      radioiodine scan in 1 case, and on radionuclide liver scan in 1 patient. Three
      patients had noniodide concentrating hepatic metastasis which were treated with
      chemotherapy but with poor response. The remaining 8 patients were treated with
      radioiodine. The survival rate was poor but could not be attributed to liver
      metastasis per se because of the extensive metastatic disease at other sites.

PMID- 9001197
TI  - Prognostic impact of thyroid lymphocytic infiltration in patients with medullary
      thyroid carcinoma.
AB  - A retrospective search for lymphocytic infiltration of the thyroid was performed
      on archival paraffin specimens from 95 cases of thyroid medullary carcinoma
      observed at a single institution during a 30-year period. A mild lymphocytic
      infiltration of the nonneoplastic thyroid tissue, mainly concentrated at the edge
      of the tumor mass, was observed in 33 cases, while in a further 24 cases a
      moderate to marked lymphocytic infiltration, resembling that seen in chronic
      lymphocytic thyroiditis, was homogeneously distributed all over the gland, with
      no apparent relationship to the site of the primary tumor. Virtually no
      lymphocytic infiltration was detected inside of any of the tumors. The presence
      of chronic lymphocytic thyroiditis seemed to be a characteristic of the host
      rather than a tumor-induced event. Statistical univariate analysis of relapse
      free survival and overall survival showed that lack of chronic lymphocytic
      thyroiditis marked those patients with an increased risk of disease recurrence
      and death. However, the observed risk for survival was statistically
      nonsignificant, whereas that for disease recurrence was significant and remained
      in a multivariate model of statistical analysis.

PMID- 9001198
TI  - Difficulty in differentiating thyrotropin secreting pituitary microadenoma from
      pituitary-selective thyroid hormone resistance accompanied by pituitary
      incidentaloma.
AB  - A 33-year-old woman with inappropriate secretion of TSH and a 2-mm pituitary
      microadenoma is described. She had a high serum free T4 concentration (31 pmol/L)
      with an inappropriately nonsuppressible serum TSH concentration (0.93 mU/L). The
      alpha/TSH molar ratio was 2.3 and magnetic resonance imaging with gadolinium
      enhancement identified an area of low signal intensity in the left lateral
      pituitary gland. However, TSH secretion was not completely autonomous. There was
      a significant response to exogenous TRH stimulation and suppression by T3
      administration. Therefore, it was difficult to rule out a nonfunctioning
      pituitary adenoma with concomitant pituitary selective thyroid hormone resistance
      syndrome. A 2-mm microadenoma was excised via transsphenoidal surgery. The tumor
      cells were immunoreactive to antisera to alpha-subunit and minimally
      immunoreactive to antisera to TSHbeta. The patient's thyroid function normalized
      after surgery without medication. Because the adenoma could become large and
      intractable if the patient was treated inadequately, early diagnosis and
      treatment are important in patients with TSH secreting adenomas.

PMID- 9001199
TI  - Expression and regulation of G protein-coupled receptor kinase 5 and beta
      arrestin-1 in rat thyroid FRTL5 cells.
AB  - G protein-coupled receptor kinases (GRKs) and arrestins are implicated in
      homologous desensitization of G protein-coupled receptors. We have recently
      demonstrated that among six GRKs so far identified, GRK5 is the isoform
      predominantly expressed in the thyroid and appears to be mainly involved in
      homologous desensitization of thyrotropin receptor (TSHR) in FRTL5 cells. To
      further understand the molecular mechanisms of the TSHR desensitization, the
      expression and regulation of GRKs and arrestins together with those of the TSHR
      were examined in FRTL5 cells. Northern blot analysis of total RNA from FRTL5
      cells with the available rat GRK cDNAs (GRK4, 5, and 6) as probes showed that
      only GRK5 mRNAs of approximately 3, 8, and 10 kilo bases (kb) in length were
      detectable. When probed with rat beta-arrestin-1 and beta-arrestin-2 cDNAs, beta
      arrestin-1 mRNAs of approximately 7.5 and 2.5 kb long, but no (or possibly faint)
      approximately 2.4 kb beta-arrestin-2 mRNA, were observed, suggesting that in the
      thyroid, beta-arrestins appear to be predominantly of beta-arrestin-1 isoform. In
      studies on TSH-regulation of GRK5, beta-arrestin-1 and TSHR mRNAs, steady-state
      levels of GRK5 and TSHR mRNAs were 3- to 4-fold lower in the cells grown in the
      medium with TSH than in those without TSH, while betaarrestin-1 mRNA levels were
      unchanged. Downregulation of GRK5 and TSHR mRNAs by TSH was further confirmed by
      dose- and time-dependent experiments. Incubation with 1mM 8BrcAMP, a cAMP analog,
      for 24h fully reproduced this TSH inhibitory effect. A decrease in GRK5 protein
      by TSH was also confirmed with Western blot analysis. In summary, these data
      together with our previous data suggested that GRK5 and beta-arrestin-1 seem to
      be the isoforms predominantly expressed in the thyroid, and they appear to play a
      pivotal role in TSHR homologous desensitization. We also demonstrated TSH
      downregulation of GRKS, but not beta-arrestin-1, expression. Further studies will
      be necessary to elucidate how these phenomena are linked to thyroid
      pathophysiology.

PMID- 9001200
TI  - mRNA encoding human thyroglobulin's C-terminus is heterogeneous.
AB  - Thyroglobulin (Tg) provides the peptide backbone for synthesis for thyroid
      hormones. Because previous studies by various techniques have raised the
      possibility of heterogeneity in Tg's message and translated protein, we have
      applied a highly sensitive ribonuclease protection assay (RPA) to examine the
      mRNA species translating part of Tg's C-terminal region, an area containing three
      of Tg's hormonogenic sites. Tissue samples were obtained from 18 normal and
      diseased human thyroids at surgery. Three probes spanning part or all of the
      nucleotide segment containing bases 7808-8086 in the cDNA sequence, detected full
      length mRNAs as the dominant transcripts but also showed the consistent presence
      of at least seven discrete smaller mRNA species in the thyroid samples. The
      amounts of these smaller mRNAs varied among tissue samples without a discernible
      relationship to the underlying clinical thyroid condition. We conclude that the
      mRNA for this region of Tg is quite heterogeneous and offers potential
      opportunities for translation of different peptide sequences that might affect
      hormonogenesis in the C-terminal region of the protein.

PMID- 9001201
TI  - Thyroid hormones as neurotransmitters.
AB  - During brain development, before the apparatus of neurotransmission has been set
      into place, many neurotransmitters act as growth regulators. In adult brain,
      their role in neurotransmission comes to the fore but neuronal plasticity and
      other growth-related processes are their continuing responsibility. This has been
      clearly demonstrated for catecholamines. Previous as well as recent evidence now
      indicates that thyroid hormones may participate in the developing and adult brain
      through similar mechanisms. Immunohistochemical mapping of brain triiodothyronine
      (antibody specificity established by numerous appropriate tests) demonstrated
      that the hormone was concentrated in both noradrenergic centers and noradrenergic
      projection sites. In the centers (locus coeruleus and lateral tegmental system)
      triiodothyronine staining, like that of tyrosine hydroxylase, was heavily
      concentrated in cytosol and cell processes. By contrast, in noradrenergic
      targets, label was most prominent in cell nuclei. Combined biochemical and
      morphologic data allows a construct of thyroid hormone circuitry to unfold: The
      locus coeruleus is conveniently located just beneath the ependyma of the 4th
      ventricle. Thyroxine, entering the brain via the choroid plexus, is
      preferentially delivered to subependymal brain structures. High concentrations of
      locus coeruleus norepinephrine promote active conversion of thyroxine to
      triiodothyronine, leading to the preeminence of the locus coeruleus as a site of
      triiodothyronine concentration. Results of treatment with the locus coeruleus
      neurotoxin DSP-4 established that axonal transport accounts for delivery of both
      triiodothyronine and norepinephrine from locus coeruleus to noradrenergic
      terminal fields. The apparatus for transduction of thyronergic and noradrenergic
      signals at both membrane and nuclear sites resides in the postsynaptic target
      cells. Upon internalization of hormone in post-synaptic target cells, genomic
      effects of triiodothyronine, norepinephrine, and/or their second messengers are
      possible and expected. The evidence establishes a direct morphologic connection
      between central thyronergic and noradrenergic systems, supporting earlier
      proposals that triiodothyronine or its proximate metabolites may serve as
      cotransmitters with norepinephrine in the adrenergic nervous system.

PMID- 9001202
TI  - Plasma thyroid hormone profiles immediately following out-of-hospital cardiac
      arrest.
AB  - Previous studies have shown abnormal thyroid hormone profiles during cardiac
      arrest. We explored this association further by characterizing plasma thyroid
      hormone profiles in 473 patients with out-of-hospital cardiac arrest and
      correlating them with clinical outcomes. Paramedics collected blood at the end of
      attempted resuscitation regardless of success. Bloods were collected and
      processed in a similar manner from 18 control subjects randomly selected from the
      community. Total thyroxine and total triiodothyronine were lower and reverse
      triiodothyronine and thyrotropin were higher in cardiac arrest patients than
      control subjects (all p < 0.001). Except for reverse triiodothyronine, findings
      were similar for a subgroup of cardiac arrest patients considered to be
      previously healthy (n = 30). Being discharged alive was associated with total
      thyroxine, total triiodothyronine and reverse triiodothyronine concentrations
      closer to the control range and thyrotropin concentrations farther from it,
      namely higher. In a multivariate stepwise model, only total triiodothyronine and
      thyrotropin were significantly associated with outcome. Whether these profoundly
      abnormal profiles represent a pre-existing state or a sudden change of thyroid
      hormone concentrations cannot be answered with this retrospective study. These
      observations suggest that thyroid hormones may play a role in the etiology of
      cardiac arrest, its prognosis, or both.

PMID- 9001203
TI  - Graves' dermopathy.

PMID- 9001204
TI  - Benzodiazepine and remission of Graves' disease.

PMID- 9001205
TI  - Transcription-dependent induction of G1 phase during the zebra fish midblastula
      transition.
AB  - The early development of the zebra fish (Danio rerio) embryo is characterized by
      a series of rapid and synchronous cell cycles with no detectable transcription.
      This period is followed by the midblastula transition (MBT), during which the
      cell cycle gradually lengthens, cell synchrony is lost, and zygotic transcription
      is initially detected. In this work, we examined the changes in the pattern of
      the cell cycle during MBT in zebra fish and whether these changes are dependent
      on the initiation of zygotic transcription. To characterize the pattern of the
      early zebra fish cell cycles, the embryonic DNA content was determined by flow
      cytometric analysis. We found that G1 phase is below detection levels during the
      first 10 cleavages and can be initially detected at the onset of MBT. Inhibition
      of zygotic transcription, by microinjection of actinomycin D, abolished the
      appearance of G1 phase at MBT. Premature activation of zygotic transcription, by
      microinjection of nonspecific DNA, induced G1 phase before the onset of MBT,
      while coinjection of actinomycin D and nonspecific DNA abolished this early
      appearance of G1 phase. We therefore suggest that during the early development of
      the zebra fish embryo, G1 phase appears at the onset of MBT and that the
      activation of transcription at MBT is essential and sufficient for the G1-phase
      induction.

PMID- 9001206
TI  - A novel, transformation-relevant activation domain in Fos proteins.
AB  - We have previously demonstrated that transformation by Fos is critically
      dependent on an intact DNA-binding domain (bZip) and a functional N-terminal
      transactivation motif (N-TM). We now show that a novel motif (C-terminal
      transactivation motif [C-TM]) near the C terminus also plays an important role in
      both transformation and the activation of AP1-dependent transcription and that
      the hydrophobic amino acids in the C-TM are functionally essential. The C-TM is
      the most crucial element in the C-terminal transactivation domain in Fos, as
      indicated by its relative strength and context-independent function. The C-TM is
      clearly different from the previously identified HOB2 domain, located N
      terminally to the C-TM, and the C-terminally positioned TATA-binding protein
      binding domain. We also show that the C-terminal transactivation domain strongly
      synergizes with the HOB1-like N-TM, even when both domains are present on
      different proteins within a dimeric complex, and that the C-TM plays a crucial
      role in this cooperation. These observations can be corroborated in a model in
      which multiple contacts with the basal machinery are established either to
      stabilize the transcription complex or to facilitate its sequential assembly.

PMID- 9001207
TI  - Hir1p and Hir2p function as transcriptional corepressors to regulate histone gene
      transcription in the Saccharomyces cerevisiae cell cycle.
AB  - The HIR/HPC (histone regulation/histone periodic control) negative regulators
      play important roles in the transcription of six of the eight core histone genes
      during the Saccharomyces cerevisiae cell cycle. The phenotypes of hir1 and hir2
      mutants suggested that the wild-type HIR1 and HIR2 genes encode transcriptional
      repressors that function in the absence of direct DNA binding. When Hir1p and
      Hir2p were artificially tethered to yeast promoters, each protein repressed
      transcription, suggesting that they represent a new class of transcriptional
      corepressors. The two proteins might function as a complex in vivo: Hir2p
      required both Hir1p and another Hir protein, Hir3p, to repress transcription when
      it was tethered to an HTA1-lacZ reporter gene, and Hir1p and Hir2p could be
      coimmunoprecipitated from yeast cell extracts. Tethered Hir1p also directed the
      periodic transcription of the HTA1 gene and repressed HTA1 transcription in
      response to two cell cycle regulatory signals. Thus, it represents the first
      example of a transcriptional corepressor with a direct role in cell cycle
      regulated transcription.

PMID- 9001208
TI  - CDC45, a novel yeast gene that functions with the origin recognition complex and
      Mcm proteins in initiation of DNA replication.
AB  - The CDC45 gene of Saccharomyces cerevisiae was isolated by complementation of the
      cold-sensitive cdc45-1 mutant and shown to be essential for cell viability.
      Although CDC45 genetically interacts with a group of MCM genes (CDC46, CDC47, and
      CDC54), the predicted sequence of its protein product reveals no significant
      sequence similarity to any known Mcm family member. Further genetic
      characterization of the cdc45-1 mutant demonstrated that it is synthetically
      lethal with orc2-1, mcm2-1, and mcm3-1. These results not only reveal a
      functional connection between the origin recognition complex (ORC) and Cdc45p but
      also extend the CDC45-MCM genetic interaction to all known MCM family members
      that were shown to be involved in replication initiation. Initiation of DNA
      replication in cdc45-1 cells was defective, causing a delayed entry into S phase
      at the nonpermissive temperature, as well as a high plasmid loss rate which could
      be suppressed by tandem copies of replication origins. Furthermore, two
      dimensional gels directly showed that chromosomal origins fired less frequently
      in cdc45-1 cells at the nonpermissive temperature. These findings suggest that
      Cdc45p, ORC, and Mcm proteins act in concert for replication initiation
      throughout the genome.

PMID- 9001209
TI  - Functional nucleotide excision repair is required for the preferential removal of
      N-ethylpurines from the transcribed strand of the dihydrofolate reductase gene of
      Chinese hamster ovary cells.
AB  - Transcription-coupled repair of DNA adducts is an essential factor that must be
      considered when one is elucidating biological endpoints resulting from exposure
      to genotoxic agents. Alkylating agents comprise one group of chemical compounds
      which modify DNA by reacting with oxygen and nitrogen atoms in the bases of the
      double helix. To discern the role of transcription-coupled DNA repair of N
      ethylpurines present in discrete genetic domains, Chinese hamster ovary cells
      were exposed to N-ethyl-N-nitrosourea, and the clearance of the damage from the
      dihydrofolate reductase gene was investigated. The results indicate that N
      ethylpurines were removed from the dihydrofolate reductase gene of nucleotide
      excision repair-proficient Chinese hamster ovary cells; furthermore, when repair
      rates in the individual strands were determined, a statistically significant bias
      in the removal of ethyl-induced, alkali-labile sites was observed, with clearance
      occurring 30% faster from the transcribed strand than from its nontranscribed
      counterpart at early times after exposure. In contrast, removal of N-ethylpurines
      was observed in the dihydrofolate reductase locus in cells that lacked nucleotide
      excision repair, but both strands were repaired at the same rate, indicating that
      transcription-coupled clearance of these lesions requires the presence of active
      nucleotide excision repair.

PMID- 9001210
TI  - The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and
      localizes to the endoplasmic reticulum and Golgi complex.
AB  - Entry into mitosis requires the activity of the Cdc2 kinase. Cdc2 associates with
      the B-type cyclins, and the Cdc2-cyclin B heterodimer is in turn regulated by
      phosphorylation. Phosphorylation of threonine 161 is required for the Cdc2-cyclin
      B complex to be catalytically active, whereas phosphorylation of threonine 14 and
      tyrosine 15 is inhibitory. Human kinases that catalyze the phosphorylation of
      threonine 161 and tyrosine 15 have been identified. Here we report the isolation
      of a novel human cDNA encoding a dual-specificity protein kinase (designated
      Myt1Hu) that preferentially phosphorylates Cdc2 on threonine 14 in a cyclin
      dependent manner. Myt1Hu is 46% identical to Myt1Xe, a kinase recently
      characterized from Xenopus laevis. Myt1Hu localizes to the endoplasmic reticulum
      and Golgi complex in HeLa cells. A stretch of hydrophobic and uncharged amino
      acids located outside the catalytic domain of Myt1Hu is the likely membrane
      targeting domain, as its deletion results in the localization of Myt1Hu primarily
      to the nucleus.

PMID- 9001211
TI  - Mos activates myogenic differentiation by promoting heterodimerization of MyoD
      and E12 proteins.
AB  - The activities of myogenic basic helix-loop-helix (bHLH) factors are regulated by
      a number of different positive and negative signals. Extensive information has
      been published about the molecular mechanisms that interfere with the process of
      myogenic differentiation, but little is known about the positive signals. We
      previously showed that overexpression of rat Mos in C2C12 myoblasts increased the
      expression of myogenic markers whereas repression of Mos products by antisense
      RNAs inhibited myogenic differentiation. In the present work, our results show
      that the rat mos proto-oncogene activates transcriptional activity of MyoD
      protein. In transient transfection assays, Mos promotes transcriptional
      transactivation by MyoD of the muscle creatine kinase enhancer and/or a reporter
      gene linked to MyoD-DNA binding sites. Physical interaction between Mos and MyoD,
      but not with E12, is demonstrated in vivo by using the two-hybrid approach with
      C3H10T1/2 cells and in vitro by using the glutathione S-transferase (GST) pull
      down assays. Unphosphorylated MyoD from myogenic cell lysates and/or bacterially
      expressed MyoD physically interacts with Mos. This interaction occurs via the
      helix 2 region of MyoD and a highly conserved region in Mos proteins with 40%
      similarity to the helix 2 domain of the E-protein class of bHLH factors.
      Phosphorylation of MyoD by activated GST-Mos protein inhibits the DNA-binding
      activity of MyoD homodimers and promotes MyoD-E12 heterodimer formation. These
      data support a novel function for Mos as a mediator (coregulator) of muscle
      specific gene(s) expression.

PMID- 9001212
TI  - Molecular cloning of human FKBP51 and comparisons of immunophilin interactions
      with Hsp90 and progesterone receptor.
AB  - A cDNA for human FKBP51 has been cloned and sequenced, and protein products have
      been expressed in both in vitro and bacterial systems. The deduced amino acid
      sequence for human FKBP51 is 90% identical to sequences of recently described
      murine proteins and is 55% identical to the sequence of human FKBP52. Human
      FKBP51 mRNA is expressed in a wide range of tissues, and the protein has
      peptidylprolyl isomerase activity that is inhibited by FK506 but not
      cyclosporine. FKBP51 is the same as a previously described progesterone receptor
      associated immunophilin that, similar to FKBP52 and cyclophilin 40, is an Hsp90
      binding protein and appears in functionally mature steroid receptor complexes
      along with Hsp90 and p23. Each of the three receptor-associated immunophilins
      displays interactions with progesterone receptor that are more dynamic than Hsp90
      receptor interactions. Whereas FKBP52 and FKBP51 compete about equally well for
      binding to Hsp90 in a purified system, FKBP51 accumulates preferentially in
      progesterone receptor complexes assembled in a cell-free system. This observation
      provides a precedent for differential interactions between Hsp90-associated
      immunophilins and target proteins such as steroid receptors.

PMID- 9001213
TI  - Expressed var genes are found in Plasmodium falciparum subtelomeric regions.
AB  - The antigenic variation and cytoadherence of Plasmodium falciparum-infected
      erythrocytes are modulated by a family of variant surface proteins encoded by the
      var multigene family. The var genes occur on multiple chromosomes, often in
      clusters, and 50 to 150 genes are estimated to be present in the haploid parasite
      genome. Transcripts from var genes have been previously mapped to internal
      chromosome positions, but the generality of such assignments and the expression
      sites and mechanisms that control switches of var gene expression are still in
      early stages of investigation. Here we describe investigations of closely related
      var genes that occur in association with repetitive elements near the telomeres
      of P. falciparum chromosomes. DNA sequence analysis of one of these genes (FCR3
      varT11-1) shows the characteristic two-exon structure encoding expected var
      features, including three variable Duffy binding-like (DBL) domains, a
      transmembrane sequence, and a carboxy-terminal segment thought to anchor the
      protein product in knobs at the surface of the parasitized erythrocyte. FCR3
      varT11-1 cross-hybridizes with var genes located close to the telomeres of many
      other P. falciparum chromosomes, including a transcribed gene (FCR3-varT3-1) in
      chromosome 3 of the P. falciparum FCR3 line. The relatively high level
      transcription from this gene shows that the polymorphic chromosome ends of P.
      falciparum, which have been proposed to be transcriptionally silent, can be
      active expression sites for var genes. The pattern of the FCR3-varT11-1 and FCR3
      varT3-1 genes are variable between different P. falciparum lines, presumably due
      to DNA rearrangements. Thus, recombination events in subtelomeric DNA may have a
      role in the expression of novel var forms.

PMID- 9001214
TI  - Regulation of Pdha-2 expression is mediated by proximal promoter sequences and
      CpG methylation.
AB  - Spermatogenesis is a complex process requiring the coordinate expression of a
      number of testis-specific genes. One of these, Pdha-2, codes for the murine
      spermatogenesis-specific isoform of the E1a subunit of the pyruvate dehydrogenase
      complex. To begin to delineate the mechanisms regulating its expression in vivo,
      we have generated transgenic mice lines carrying Pdha-2 promoter deletion
      constructs. Here we report that transgenic mice harboring a construct containing
      only 187 bp of promoter and upstream sequences (core promoter) is sufficient for
      directing the testis-specific expression of a chloramphenicol acetyltransferase
      (CAT) reporter gene. Like the endogenous Pdha-2, the CAT gene is expressed in
      testis in a stage-specific manner. Our studies also show a correlation between
      CpG methylation within the core promoter and its capacity to regulate
      transcription. In NIH 3T3 cell lines stably transfected with the Pdha-2 core
      promoter-CAT construct, high levels of CAT reporter expression are observed,
      whereas the endogenous Pdha-2 gene is repressed. In these cells, the CpG
      dinucleotides residing within the transfected promoter are hypomethylated whereas
      those residing in the endogenous promoter are methylated. Furthermore, promoter
      activity can be abated by the in vitro methylation of its CpG dinucleotides.
      DNase I footprint analysis indicates that at least one site for the methylation
      mediated repression may occur through the ATF/cyclic AMP response element binding
      element located within the core promoter. Mutations within this element reduces
      activity to approximately 50% of the wild-type promoter activity. These results
      suggest that tissue-specific gene expression may be modulated by other mechanisms
      in addition to specific transcription factor availability and cooperativity. We
      propose that methylation may be a mechanism by which repression of the testis
      specific Pdha-2 gene is established in somatic tissue.

PMID- 9001215
TI  - Cdc55p, the B-type regulatory subunit of protein phosphatase 2A, has multiple
      functions in mitosis and is required for the kinetochore/spindle checkpoint in
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae, like most eucaryotic cells, can prevent the onset of
      anaphase until chromosomes are properly aligned on the mitotic spindle. We
      determined that Cdc55p (regulatory B subunit of protein phosphatase 2A [PP2A]) is
      required for the kinetochore/spindle checkpoint regulatory pathway in yeast.
      ctf13 cdc55 double mutants could not maintain a ctf13-induced mitotic delay, as
      determined by antitubulin staining and levels of histone H1 kinase activity. In
      addition, cdc55::LEU2 mutants and tpd3::LEU2 mutants (regulatory A subunit of
      PP2A) were nocodazole sensitive and exhibited the phenotypes of previously
      identified kinetochore/spindle checkpoint mutants. Inactivating CDC55 did not
      simply bypass the arrest that results from inhibiting ubiquitin-dependent
      proteolysis because cdc16-1 cdc55::LEU2 and cdc23-1 cdc55::LEU2 double mutants
      arrested normally at elevated temperatures. CDC55 is specific for the
      kinetochore/spindle checkpoint because cdc55 mutants showed normal sensitivity to
      gamma radiation and hydroxyurea. The conditional lethality and the abnormal
      cellular morphogenesis of cdc55::LEU2 were suppressed by cdc28F19, suggesting
      that the cdc55 phenotypes are dependent on the phosphorylation state of Cdc28p.
      In contrast, the nocodazole sensitivity of cdc55::LEU2 was not suppressed by
      cdc28F19. Therefore, the mitotic checkpoint activity of CDC55 (and TPD3) is
      independent of regulated phosphorylation of Cdc28p. Finally, cdc55::LEU2
      suppresses the temperature sensitivity of cdc20-1, suggesting additional roles
      for CDC55 in mitosis.

PMID- 9001216
TI  - Efficient gap repair in Drosophila melanogaster requires a maximum of 31
      nucleotides of homologous sequence at the searching ends.
AB  - Double-strand breaks (DSB) were generated in the Drosophila melanogaster white
      gene by excision of the P-w(hd) element. An ectopic P-element vector carrying a
      modified white gene was used as a template for DSB repair. All template-dependent
      repair events were examined, and four different classes of events were recovered.
      The two most common products observed were gene conversions external to the P
      w(hd) element and gene conversions (targeted transpositions) internal to the P
      w(hd) element. These two events were equally frequent. Similar numbers for both
      orientations of internal conversion events were recovered. The results suggest
      that P-element excision occurs by a staggered cut that leaves behind at least 33
      nucleotides of single-stranded sequence. Our results further demonstrate that an
      efficient homology search is conducted by the broken end with less than 31
      nucleotides.

PMID- 9001217
TI  - The RAD7, RAD16, and RAD23 genes of Saccharomyces cerevisiae: requirement for
      transcription-independent nucleotide excision repair in vitro and interactions
      between the gene products.
AB  - Nucleotide excision repair (NER) is a biochemical process required for the repair
      of many different types of DNA lesions. In the yeast Saccharomyces cerevisiae,
      the RAD7, RAD16, and RAD23 genes have been specifically implicated in NER of
      certain transcriptionally repressed loci and in the nontranscribed strand of
      transcriptionally active genes. We have used a cell-free system to study the
      roles of the Rad7, Rad16, and Rad23 proteins in NER. Transcription-independent
      NER of a plasmid substrate was defective in rad7, rad16, and rad23 mutant
      extracts. Complementation studies with a previously purified NER protein complex
      (nucleotide excision repairosome) indicate that Rad23 is a component of the
      repairosome, whereas Rad7 and Rad16 proteins were not found in this complex.
      Complementation studies with rad4, rad7, rad16, and rad23 mutant extracts suggest
      physical interactions among these proteins. This conclusion was confirmed by
      experiments using the yeast two-hybrid assay, which demonstrated the following
      pairwise interactions: Rad4 with Rad23, Rad4 with Rad7, and Rad7 with Rad16.
      Additionally, interaction between the Rad7 and Rad16 proteins was demonstrated in
      vitro. Our results show that Rad7, Rad16, and Rad23 are required for
      transcription-independent NER in vitro. This process may involve a unique protein
      complex which is distinct from the repairosome and which contains at least the
      Rad4, Rad7, and Rad16 proteins.

PMID- 9001219
TI  - A combination of MEF3 and NFI proteins activates transcription in a subset of
      fast-twitch muscles.
AB  - The human aldolase A pM promoter is active in fast-twitch muscles. To understand
      the role of the different transcription factors which bind to this promoter and
      determine which ones are responsible for its restricted pattern of expression, we
      analyzed several transgenic lines harboring different combinations of pM
      regulatory elements. We show that muscle-specific expression can be achieved
      without any binding sites for the myogenic factors MyoD and MEF2 and that a 64-bp
      fragment comprising a MEF3 motif and an NFI binding site is sufficient to drive
      reporter gene expression in some but, interestingly, not all fast-twitch muscles.
      A result related to this pattern of expression is that some isoforms of NFI
      proteins accumulate differentially in fast- and slow-twitch muscles and in
      distinct fast-twitch muscles. We propose that these isoforms of NFI proteins
      might provide a molecular basis for skeletal muscle diversity.

PMID- 9001218
TI  - Retinoid X receptor (RXR) within the RXR-retinoic acid receptor heterodimer binds
      its ligand and enhances retinoid-dependent gene expression.
AB  - Retinoic acid receptor (RAR) and retinoid X receptor (RXR) form heterodimers and
      regulate retinoid-mediated gene expression. We studied binding of RXR- and RAR
      selective ligands to the RXR-RAR heterodimer and subsequent transcription. In
      limited proteolysis analyses, both RXR and RAR in the heterodimer bound their
      respective ligands and underwent a conformational change in the presence of a
      retinoic acid-responsive element. In reporter analyses, the RAR ligand (but not
      the RXR ligand), when added singly, activated transcription, but coaddition of
      the two ligands led to synergistic activation of transcription. This activation
      required the AF-2 domain of both RXR and RAR. Genomic footprinting analysis was
      performed with P19 embryonal carcinoma cells, in which transcription of the
      RARbeta gene is induced upon retinoid addition. Paralleling the reporter
      activation data, only the RAR ligand induced in vivo occupancy of the RARbeta2
      promoter when added singly. However, at suboptimal concentrations of RAR ligand,
      coaddition of the RXR ligand increased the stability of promoter occupancy. Thus,
      liganded RXR and RAR both participate in transcription. Finally, when these
      ligands were tested for teratogenic effects on zebra fish and Xenopus embryos, we
      found that coadministration of the RXR and RAR ligands caused more severe
      abnormalities in these embryos than either ligand alone, providing biological
      support for the synergistic action of the two ligands.

PMID- 9001221
TI  - The intracisternal A-particle proximal enhancer-binding protein activates
      transcription and is identical to the RNA- and DNA-binding protein p54nrb/NonO.
AB  - The long terminal repeats of murine intracisternal A particles (IAPs) contain an
      IAP proximal enhancer (IPE) element that is inactive in murine F9 embryonal
      carcinoma cells and active in the parietal endoderm cell line PYS-2. The element
      binds efficiently to a 60-kDa IPE-binding protein (IPEB) present in PYS-2 cells
      but poorly to F9 proteins, suggesting a role for IPEB in regulating IAP
      expression. We have purified calf thymus IPEB, which binds to the IPE and
      transactivates a reporter gene in HeLa cell extracts. Based on the peptide
      sequence of the purified calf IPEB, we have cloned a 420-bp cDNA and showed that
      the encoded protein is the homolog of human p54nrb and mouse NonO, which are
      characterized by the presence of two RNA recognition motifs. We show that p54nrb
      is an IPE-binding transcription activator with its DNA-binding and activation
      domains in the N- and C-terminal halves, respectively. The activation domain of
      p54nrb is active in HeLa, PYS-2, and F9 cells, whereas p54nrb as a whole molecule
      is active in HeLa and PYS-2 cells but not in F9 cells. Thus, the lack of activity
      of p54nrb in F9 cells is due to an ineffective DNA-binding domain. We demonstrate
      that p54nrb also binds to a pre-mRNA. Based on the close sequence relatedness of
      this protein to PSF, which is required for pre-mRNA splicing in vitro, we discuss
      the possibility that p54nrb has dual roles in transcription and splicing.

PMID- 9001220
TI  - Characterization of reaper- and FADD-induced apoptosis in a lepidopteran cell
      line.
AB  - Expression of the reaper gene (rpr) correlates with the initiation of apoptosis
      in Drosophila melanogaster. Transient expression of rpr in the lepidopteran SF-21
      cell line induced apoptosis displaying nuclear condensation and fragmentation,
      oligonucleosomal ladder formation, cell surface blebbing, and apoptotic body
      formation. Inhibitors of ICE-family proteases p35 and crmA, as well as members of
      the iap class of genes, Op-iap and D-iap2, but not bcl-2 family members, blocked
      rpr-induced apoptosis. Mutational analysis of rpr provided no support for the
      proposed sequence similarity of Reaper and death domain proteins. Mutations in
      the N-terminal region of Reaper, which displays sequence similarity to Hid and
      Grim, other Drosophila gene products correlated with the initiation of apoptosis,
      suggested that these residues might be functionally important. The mammalian cDNA
      encoding FADD (Fas-associating protein with a death domain) also induced cell
      death in SF-21 cells, but death progressed more slowly and with features which
      distinguished it from rpr-induced apoptosis. Several bcl-2 family members delayed
      or blocked FADD-induced cellular death. Thus, apoptosis initiated by Reaper
      progressed by a faster path which appeared to differ from that of FADD-induced
      apoptosis.

PMID- 9001222
TI  - HNF4beta, a new gene of the HNF4 family with distinct activation and expression
      profiles in oogenesis and embryogenesis of Xenopus laevis.
AB  - The transcription factor hepatocyte nuclear factor 4 (HNF4) is an orphan member
      of the nuclear receptor superfamily expressed in mammals in liver, kidney, and
      the digestive tract. Recently, we isolated the Xenopus homolog of mammalian HNF4
      and revealed that it is not only a tissue-specific transcription factor but also
      a maternal component of the Xenopus egg and distributed within an animal-to
      vegetal gradient. We speculate that this gradient cooperates with the vegetally
      localized embryonic induction factor activin A to activate expression of
      HNF1alpha, a tissue-specific transcription factor with an expression pattern
      overlapping that of HNF4. We have now identified a second Xenopus HNF4 gene,
      which is more distantly related to mammalian HNF4 than the previously isolated
      gene. This new gene was named HNF4beta to distinguish it from the known HNF4
      gene, which is now called HNF4alpha. By reverse transcription-PCR, we detected
      within the 5' untranslated region of HNF4beta two splice variants (HNF4beta2 and
      HNF4beta3) with additional exons, which seem to affect RNA stability. HNF4beta is
      a functional transcription factor acting sequence specifically on HNF4 binding
      sites known for HNF4alpha, but it seems to have a lower DNA binding activity and
      is a weaker transactivator than the alpha isoform. Furthermore, the two factors
      differ with respect to tissue distribution in adult frogs: whereas HNF4alpha is
      expressed in liver and kidney, HNF4beta is expressed in addition in stomach,
      intestine, lung, ovary, and testis. Both factors are maternal proteins and
      present at constant levels throughout embryogenesis. However, using reverse
      transcription-PCR, we found the RNA levels to change substantially: whereas
      HNF4alpha is expressed early during oogenesis and is absent in the egg, HNF4beta
      is first detected in the latest stage of oogenesis, and transcripts are present
      in the egg and early cleavage stages. Furthermore, zygotic HNF4alpha transcripts
      appear in early gastrula and accumulate during further embryogenesis, whereas
      HNF4beta mRNA transiently appears during gastrulation before it accumulates again
      at the tail bud stage. All of these distinct characteristics of the newly
      identified HNF4 protein imply that the alpha and beta isoform have different
      functions in development and in adult tissues.

PMID- 9001224
TI  - A unique downregulation of h2-calponin gene expression in Down syndrome: a
      possible attenuation mechanism for fetal survival by methylation at the CpG
      island in the trisomic chromosome 21.
AB  - To understand the effect of trisomic chromosome 21 on the cause of Down syndrome
      (DS), DNA methylation in the CpG island, which regulates the expression of
      adjacent genes, was investigated with the DNAs of chromosome 21 isolated from DS
      patients and their parents. A methylation-sensitive enzyme, BssHII, was used to
      digest DNAs of chromosome 21, and the resulting DNA fragments were subjected to
      RLGS (restriction landmark genomic scanning). Surprisingly, the CpG island of the
      h2-calponin gene was shown to be specifically methylated by comparative studies
      with RLGS and Southern blot analysis. In association with this methylation, h2
      calponin gene expression was attenuated to the normal level, although other genes
      in the DS region of chromosome 21 were expressed dose dependently at 1.5 times
      the normal level. These results and the high miscarriage rate associated with
      trisomy 21 embryos imply that the altered in vivo methylation that attenuates
      downstream gene expression, which is otherwise lethal, permits the generation of
      DS neonates. The h2-calponin gene detected by the RLGS procedure may be one such
      gene that is attenuated.

PMID- 9001223
TI  - A JAK1/JAK2 chimera can sustain alpha and gamma interferon responses.
AB  - Cell lines that are mutated in interferon (IFN) responses have been critical in
      establishing an essential role for the JAK family of nonreceptor tyrosine kinases
      in interferon signalling. Mutant gamma1A cells have previously been shown to be
      complemented by overexpression of JAK2. Here, it is shown that these cells carry
      a defect in, and can also be complemented by, the beta-subunit of the IFN-gamma
      receptor, consistent with the hypothesis that the mutation in these cells affects
      JAK2-receptor association. In contrast, mutant gamma2A cells lack detectable JAK2
      mRNA and protein. By using gamma2A cells, the role of various domains and
      conserved tyrosine residues of JAK2 in IFN-gamma signalling was examined.
      Individual mutation of six conserved tyrosine residues, mutation of a potential
      phosphatase binding site, or mutation of the arginine residue in the proposed SH2
      like domain had no apparent effect on signalling in response to IFN-gamma.
      Results with deletion mutants, however, indicated that association of JAK2 with
      the IFN-gammaR2 subunit requires the amino-terminal region but not the
      pseudokinase domain. Consistent with this, in chimeras with JAK1, the JAK2 amino
      terminal region was required for receptor association and STAT1 activation.
      Conversely, a JAK1-JAK2 chimera with the amino-terminal domains of JAK1 linked to
      the pseudokinase and kinase domains of JAK2 is capable of reconstituting JAK-STAT
      signalling in response to IFN-alpha and -gamma in mutant U4C cells lacking JAK1.
      The specificity of the JAKs may therefore lie mainly in their structural
      interaction with different receptor and signalling proteins rather than in the
      substrate specificity of their kinase domains.

PMID- 9001225
TI  - The murine C'-terminally alternatively spliced form of p53 induces attenuated
      apoptosis in myeloid cells.
AB  - The onset of p53-dependent apoptosis results from the accumulation of damaged
      DNA. Recently, it was shown that the C' terminus of the p53 protein plays a
      central role in sensing damaged DNA. In our present study, we examined the role
      of the C' terminus in the induction of apoptosis. A temperature-sensitive (ts)
      mutant of the alternatively spliced form of p53 (p53AS-ts) and the ts mutant of
      the regularly spliced form (p53RS-ts) were used to generate series of stable
      clones with increasing amounts of p53 protein. Apoptotic patterns induced by
      either the regularly spliced p53 product (p53RS) or a C'-terminally alternatively
      spliced p53 product (p53AS) were compared. We found that although both forms of
      p53 induced apoptosis following expression of the wild-type protein conformation,
      the kinetics were different. Apoptosis induced by the p53AS protein was
      attenuated compared to that induced by p53RS. The delay in the manifestation of
      the apoptotic features following p53AS expression was in agreement with a delay
      in the regulation of the expression of apoptosis-related genes. The observation
      that p53 with an altered C' terminus is still capable of inducing apoptosis
      suggests that the actual onset of the apoptotic process most probably involves
      structural domains other than the C' terminus of the p53 molecule. However, the
      fact that the apoptotic activity mediated by the p53AS product was slower than
      that mediated by the p53RS product suggests that the C' terminus indeed exerts a
      certain control on the apoptotic activity of the p53 molecule.

PMID- 9001226
TI  - Increased tumor proliferation and genomic instability without decreased apoptosis
      in MMTV-ras mice deficient in p53.
AB  - We have used an in vivo tumor model to evaluate the consequences of p53 tumor
      suppressor protein deficiency in a tissue-specific context. By breeding MMTV-ras
      transgenic mice, which are highly susceptible to the development of mammary and
      salivary tumors, with p53(-/-) mice, we generated three classes of animals which
      contained the MMTV-ras transgene but differed in their p53 functional status
      (ras/p53(+/+), ras/p53(+/-), or ras/p53(-/-)). ras/p53(-/-) mice developed tumors
      more rapidly than animals of the other two genotypes; however, the distribution
      of tumors was unexpectedly altered. Whereas the most frequently observed tumors
      in ras/p53(+/+) and ras/p53(+/-) mice were of mammary origin, ras/p53(-/-) mice
      developed primarily salivary tumors. In addition, the mammary and salivary tumors
      from ras/p53(-/-) mice consistently exhibited a number of unfavorable
      characteristics, including higher histologic grades, increased growth rates, and
      extensive genomic instability and heterogeneity, relative to tumors from
      ras/p53(+/+) mice. Interestingly, the increased growth rates of ras/p53(-/-)
      tumors appear to be due to impaired cell cycle regulation rather than decreased
      apoptosis, suggesting that p53-mediated tumor suppression can occur independent
      of its role in apoptosis.

PMID- 9001227
TI  - Role of diacylglycerol-regulated protein kinase C isotypes in growth factor
      activation of the Raf-1 protein kinase.
AB  - The Raf protein kinases function downstream of Ras guanine nucleotide-binding
      proteins to transduce intracellular signals from growth factor receptors.
      Interaction with Ras recruits Raf to the plasma membrane, but the subsequent
      mechanism of Raf activation has not been established. Previous studies implicated
      hydrolysis of phosphatidylcholine (PC) in Raf activation; therefore, we
      investigated the role of the epsilon isotype of protein kinase C (PKC), which is
      stimulated by PC-derived diacylglycerol, as a Raf activator. A dominant negative
      mutant of PKC epsilon inhibited both proliferation of NIH 3T3 cells and
      activation of Raf in COS cells. Conversely, overexpression of active PKC epsilon
      stimulated Raf kinase activity in COS cells and overcame the inhibitory effects
      of dominant negative Ras in NIH 3T3 cells. PKC epsilon also stimulated Raf kinase
      in baculovirus-infected Spodoptera frugiperda Sf9 cells and was able to directly
      activate Raf in vitro. Consistent with its previously reported activity as a Raf
      activator in vitro, PKC alpha functioned similarly to PKC epsilon in both NIH 3T3
      and COS cell assays. In addition, constitutively active mutants of both PKC alpha
      and PKC epsilon overcame the inhibitory effects of dominant negative mutants of
      the other PKC isotype, indicating that these diacylglycerol-regulated PKCs
      function as redundant activators of Raf-1 in vivo.

PMID- 9001228
TI  - A fission yeast homolog of CDC20/p55CDC/Fizzy is required for recovery from DNA
      damage and genetically interacts with p34cdc2.
AB  - Successful recovery from DNA damage requires coordination of several biological
      processes. Eukaryotic cell cycle progression is delayed when the cells encounter
      DNA-damaging agents. This cell cycle delay allows the cells to cope with DNA
      damage by utilizing DNA repair enzymes. Thus, at least two processes, induction
      of the cell cycle delay and repair of damaged DNA, are coordinately required for
      recovery. In this study, a fission yeast rad mutant (slp1-362) was genetically
      investigated. In response to radiation, slp1 stops cell division; however, it
      does not restart it. This defect is suppressed when slp1-362 is combined with
      wee1-50 or cdc2-3w; in these mutants, the onset of mitosis is advanced due to the
      premature activation of p34cdc2. In contrast, slp1 is synthetically lethal with
      cdc25, nim1/cdr1, or cdr2, all of which are unable to activate the p34cdc2 kinase
      correctly. These genetic interactions of slp1 with cdc2 and its modulators imply
      that slp1 is not defective in either "induction of cell cycle delay" or "DNA
      repair." slp1+ may be involved in a critical process which restarts cell cycle
      progression after the completion of DNA repair. Molecular cloning of slp1+
      revealed that slp1+ encodes a putative 488-amino-acid polypeptide exhibiting
      significant homology to WD-domain proteins, namely, CDC20 (budding yeast), p55CDC
      (human), and Fizzy (fly). A possible role of slp1+ is proposed.

PMID- 9001229
TI  - Role of alpha2 protein in donor locus selection during mating type
      interconversion.
AB  - The homeodomain protein alpha2p plays a role both in transcriptional repression
      in the process of cell type determination and in donor selection during mating
      interconversion. We have explored the mechanism of alpha2p-directed donor
      selection by examining the effects on donor preference of mutants deficient in
      alpha2p-mediated transcriptional repression. As a transcriptional regulator,
      alpha2p interacts with Mcm1p, Tup1p, and Ssn6p to repress a-specific genes and
      with a1p, Tup1p, and Ssn6p to repress haploid-specific genes. We have found that
      mutant alleles of MATalpha2 that specifically diminish the interaction of alpha2p
      with Mcm1p or Tup1p behave as null alleles with regard to donor preference, while
      mutations of MATalpha2 that specifically diminish interaction of alpha2p with a1p
      behave as wild-type MATalpha2 in this capacity. Tup1p plays an essential role in
      alpha2p-mediated transcriptional repression, while Ssn6p has only a modest effect
      in repression. In a similar vein, we find that TUP1, but not SSN6, is required
      for proper donor selection. These results suggest that, in addition to regulating
      a-specific gene expression to establish the mating type of the cell, alpha2p
      Mcm1p-Tup1p complex may indirectly regulate donor preference through
      transcriptional control of an a-specific gene. Alternatively, this complex may
      play a direct role in establishing donor preference via its DNA binding and
      chromatin organization capacity.

PMID- 9001231
TI  - Identification of a protein that binds to the Ho endonuclease recognition
      sequence at the yeast mating type locus.
AB  - Mating type switching in Saccharomyces cerevisiae initiates when Ho endonuclease
      makes a site-specific double-stranded break at MAT, the yeast mating type locus.
      To identify other proteins involved in this process, we examined whether extracts
      prepared from ho- mutants contain additional factors that bind near the
      recognition sequence for Ho. Using an electrophoretic mobility shift assay, we
      isolated a chromatographic fraction that contains an activity, named YZbp, which
      binds to two sequences flanking the recognition sequence at MATalpha and to one
      sequence overlapping it at MATa. MAT plasmids carrying mutations in the YZbp
      recognition sequence are cleaved by purified Ho at wild-type efficiencies in an
      in vitro assay. These same plasmids, however, are not cleaved by Ho inside cells,
      demonstrating that YZbp acts as a positive activator of in vivo cleavage. YZbp is
      present in all cell types, even those not undergoing mating type switching,
      suggesting that it has additional cellular functions.

PMID- 9001230
TI  - Recognition and repair of compound DNA lesions (base damage and mismatch) by
      human mismatch repair and excision repair systems.
AB  - Nucleotide excision repair and the long-patch mismatch repair systems correct
      abnormal DNA structures arising from DNA damage and replication errors,
      respectively. DNA synthesis past a damaged base (translesion replication) often
      causes misincorporation at the lesion site. In addition, mismatches are hot spots
      for DNA damage because of increased susceptibility of unpaired bases to chemical
      modification. We call such a DNA lesion, that is, a base damage superimposed on a
      mismatch, a compound lesion. To learn about the processing of compound lesions by
      human cells, synthetic compound lesions containing UV photoproducts or cisplatin
      1,2-d(GpG) intrastrand cross-link and mismatch were tested for binding to the
      human mismatch recognition complex hMutS alpha and for excision by the human
      excision nuclease. No functional overlap between excision repair and mismatch
      repair was observed. The presence of a thymine dimer or a cisplatin diadduct in
      the context of a G-T mismatch reduced the affinity of hMutS alpha for the
      mismatch. In contrast, the damaged bases in these compound lesions were excised
      three- to fourfold faster than simple lesions by the human excision nuclease,
      regardless of the presence of hMutS alpha in the reaction. These results provide
      a new perspective on how excision repair, a cellular defense system for
      maintaining genomic integrity, can fix mutations under certain circumstances.

PMID- 9001232
TI  - Evidence for the involvement of mouse heat shock factor 1 in the atypical
      expression of the HSP70.1 heat shock gene during mouse zygotic genome activation.
AB  - The mouse HSP70.1 gene, which codes for a heat shock protein (hsp70), is highly
      transcribed at the onset of zygotic genome activation (ZGA). This expression,
      which occurs in the absence of stress, is then repressed. It has been claimed
      that this gene does not exhibit a stress response until the blastocyst stage. The
      promoter of HSP70.1 contains four heat shock element (HSE) boxes which are the
      binding sites of heat shock transcription factors (HSF). We have been studying
      the presence and localization of the mouse HSFs, mHSF1 and mHSF2, at different
      stages of embryo development. We show that mHSF1 is already present at the one
      cell stage and concentrated in the nucleus. Moreover, by mutagenizing HSE
      sequences and performing competition experiments (in transgenic embryos with the
      HSP70.1 promoter inserted before a reporter gene), we show that, in contrast with
      previous findings, HSE boxes are involved in this spontaneous activation.
      Therefore, we suggest that HSF1 and HSE are important in this transient
      expression at the two-cell stage and that the absence of typical inducibility at
      this early stage of development results mainly from the high level of spontaneous
      transcription of this gene during the ZGA.

PMID- 9001233
TI  - Mouse U2af1-rs1 is a neomorphic imprinted gene.
AB  - The mouse U2af1-rs1 gene is an endogenous imprinted gene on the proximal region
      of chromosome 11. This gene is transcribed exclusively from the unmethylated
      paternal allele, while the methylated maternal allele is silent. An analysis of
      genome structure of this gene revealed that the whole gene is located in an
      intron of the Murr1 gene. Although none of the three human U2af1-related genes
      have been mapped to chromosome 2, the human homolog of Murr1 is assigned to
      chromosome 2. The mouse Murr1 gene is transcribed biallelically, and therefore it
      is not imprinted in neonatal mice. Allele-specific methylation is limited to a
      region around U2af1-rs1 in an intron of Murr1. These results suggest that in
      chromosomal homology and genomic imprinting, the U2af1-rs1 gene is distinct from
      the genome region surrounding it. We have proposed the neomorphic origin of the
      U2af1-rs1 gene by retrotransposition and the particular mechanism of genomic
      imprinting of ectopic genes.

PMID- 9001235
TI  - Severe growth defect in a Schizosaccharomyces pombe mutant defective in intron
      lariat degradation.
AB  - The cDNAs and genes encoding the intron lariat-debranching enzyme were isolated
      from the nematode Caenorhabditis elegans and the fission yeast
      Schizosaccharomyces pombe based on their homology with the Saccharomyces
      cerevisiae gene. The cDNAs were shown to be functional in an interspecific
      complementation experiment; they can complement an S. cerevisiae dbr1 null
      mutant. About 2.5% of budding yeast S. cerevisiae genes have introns, and the
      accumulation of excised introns in a dbr1 null mutant has little effect on cell
      growth. In contrast, many S. pombe genes contain introns, and often multiple
      introns per gene, so that S. pombe is estimated to contain approximately 40 times
      as many introns as S. cerevisiae. The S. pombe dbr1 gene was disrupted and shown
      to be nonessential. Like the S. cerevisiae mutant, the S. pombe null mutant
      accumulated introns to high levels, indicating that intron lariat debranching
      represents a rate-limiting step in intron degradation in both species. Unlike the
      S. cerevisiae mutant, the S. pombe dbr1::leu1+ mutant had a severe growth defect
      and exhibited an aberrant elongated cell shape in addition to an intron
      accumulation phenotype. The growth defect of the S. pombe dbr1::leu1+ strain
      suggests that debranching activity is critical for efficient intron RNA
      degradation and that blocking this pathway interferes with cell growth.

PMID- 9001234
TI  - Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome
      pathway.
AB  - The Met tyrosine kinase receptor is a widely expressed molecule which mediates
      pleiotropic cellular responses following activation by its ligand, hepatocyte
      growth factor/scatter factor (HGF/SF). In this communication we demonstrate that
      significant Met degradation is induced by HGF/SF and that this degradation can be
      blocked by lactacystin, an inhibitor of proteasome activity. We also show that
      Met is rapidly polyubiquitinated in response to ligand and that polyubiquitinated
      Met molecules, which are normally unstable, are stabilized by lactacystin. Both
      HGF/SF-induced degradation and polyubiquitination of Met were shown to be
      dependent on the receptor possessing intact tyrosine kinase activity. Finally, we
      found that a normally highly labile 55-kDa fragment of the Met receptor is
      stabilized by lactacystin and demonstrate that it represents a cell-associated
      remnant that is generated following the ligand-independent proteolytic cleavage
      of the Met receptor in its extracellular domain. This truncated Met molecule
      encompasses the kinase domain of the receptor and is itself tyrosine
      phosphorylated. We conclude that the ubiquitin-proteasome pathway plays a
      significant role in the degradation of the Met tyrosine kinase receptor as
      directed by ligand-dependent and -independent signals. We propose that this
      proteolytic pathway may be important for averting cellular transformation by
      desensitizing Met signaling following ligand stimulation and by eliminating
      potentially oncogenic fragments generated via extracellular cleavage of the Met
      receptor.

PMID- 9001237
TI  - Gene conversions mediating antigenic variation in Trypanosoma brucei can occur in
      variant surface glycoprotein expression sites lacking 70-base-pair repeat
      sequences.
AB  - African trypanosomes undergo antigenic variation of their variant surface
      glycoprotein (VSG) coat to avoid immune system-mediated killing by their
      mammalian host. An important mechanism for switching the expressed VSG gene is
      the duplicative transposition of a silent VSG gene into one of the telomeric VSG
      expression sites of the trypanosome, resulting in the replacement of the
      previously expressed VSG gene. This process appears to be a gene conversion
      reaction, and it has been postulated that sequences within the expression site
      may act to initiate and direct the reaction. All bloodstream form expression
      sites contain huge arrays (many kilobase pairs) of 70-bp repeat sequences that
      act as the 5' boundary of gene conversion reactions involving most silent VSG
      genes. For this reason, the 70-bp repeats seemed a likely candidate to be
      involved in the initiation of switching. Here, we show that deletion of the 70-bp
      repeats from the active expression site does not affect duplicative transposition
      of VSG genes from silent expression sites. We conclude that the 70-bp repeats do
      not appear to function as indispensable initiation sites for duplicative
      transposition and are unlikely to be the recognition sequence for a sequence
      specific enzyme which initiates recombination-based VSG switching.

PMID- 9001236
TI  - Multiple phosphorylated forms of the Saccharomyces cerevisiae Mcm1 protein
      include an isoform induced in response to high salt concentrations.
AB  - The Saccharomyces cerevisiae Mcm1 protein is an essential multifunctional
      transcription factor which is highly homologous to human serum response factor.
      Mcm1 protein acts on a large number of distinctly regulated genes: haploid cell
      type-specific genes, G2-cell-cycle-regulated genes, pheromone-induced genes,
      arginine metabolic genes, and genes important for cell wall and cell membrane
      function. We show here that Mcm1 protein is phosphorylated in vivo. Several (more
      than eight) isoforms of Mcm1 protein, resolved by isoelectric focusing, are
      present in vivo; two major phosphorylation sites lie in the N-terminal 17 amino
      acids immediately adjacent to the conserved MADS box DNA-binding domain. The
      implications of multiple species of Mcm1, particularly the notion that a unique
      Mcm1 isoform could be required for regulation of a specific set of Mcm1's target
      genes, are discussed. We also show here that Mcm1 plays an important role in the
      response to stress caused by NaCl. G. Yu, R. J. Deschenes, and J. S. Fassler (J.
      Biol. Chem. 270:8739-8743, 1995) showed that Mcm1 function is affected by
      mutations in the SLN1 gene, a signal transduction component implicated in the
      response to osmotic stress. We find that mcm1 mutations can confer either reduced
      or enhanced survival on high-salt medium; deletion of the N terminus or mutation
      in the primary phosphorylation site results in impaired growth on high-salt
      medium. Furthermore, Mcm1 protein is a target of a signal transduction system
      responsive to osmotic stress: a new isoform of Mcm1 is induced by NaCl or KCl;
      this result establishes that Mcm1 itself is regulated.

PMID- 9001238
TI  - Regulation of the pro-B-cell-specific enhancer of the Id1 gene involves the C/EBP
      family of proteins.
AB  - The Id1 protein acts as a negative regulator in early-B-cell differentiation by
      antagonizing the function of the basic helix-loop-helix transcription factors.
      Expression of the Id1 gene during B-cell development is governed at the
      transcriptional level primarily by a pro-B-cell-specific enhancer (PBE) located 3
      kb downstream of the gene. We report here the identification of CAAT/enhancer
      binding protein beta (C/EBPbeta) as a component of the two major PBE-binding
      complexes (PBEC1 and PBEC2) found in pro-B cells by gel mobility shift assays.
      Formation of the PBECs is abolished when a classic C/EBP binding site is used as
      a competitor, and binding complexes similar to the PBECs are formed when the
      classic C/EBP site is used as a probe. We show that CHOP, a negative regulator of
      C/EBPs, specifically inhibits PBE binding in vitro and its enhancer activity in
      vivo. In pro-B cells, C/EBPbeta binds to the PBE site not as apparent homodimers
      but possibly in association with at least one other polypeptide, which might
      determine the pro-B-cell-specific expression of the Id1 gene. Although isoforms
      of C/EBPbeta are expressed in various B cells, they bind to DNA only in LyD9 and
      Ba/F3 pro-B cells. We show that CHOP is expressed in 70Z/3 and WEHI-231 cells. We
      also demonstrate that CHOP is associated with C/EBPbeta in WEHI-231 cells, which
      may provide an additional mechanism to control the function of C/EBPbeta and the
      expression of the Id1 gene.

PMID- 9001240
TI  - Positive selection of FLP-mediated unequal sister chromatid exchange products in
      mammalian cells.
AB  - Site-specific recombination provides a powerful tool for studying gene function
      at predetermined chromosomal sites. Here we describe the use of a blasticidin
      resistance system to select for recombination in mammalian cells using the yeast
      enzyme FLP. The vector is designed so that site-specific recombination
      reconstructs the antibiotic resistance marker within the sequences flanked by the
      FLP target sites. This approach allows the detection of DNA excised by FLP
      mediated recombination and facilitates the recovery of recombination products
      that would not be detected by available screening strategies. We used this system
      to show that the molecules excised by intrachromosomal recombination between
      tandem FLP recombinase target sites do not reintegrate into the host genome at
      detectable frequencies. We further applied the direct selection approach to
      recover a rare FLP-mediated recombination event displaying the characteristics of
      an unequal sister chromatid exchange between FLP target sites. Implications of
      this approach for the generation of duplications to assess their effect on gene
      dosage and chromosome stability are discussed.

PMID- 9001239
TI  - In vivo analysis of DNA-protein interactions on the human erythropoietin
      enhancer.
AB  - The erythropoietin (EPO) gene is one of the best examples of a mammalian gene
      controlled by oxygen tension. The DNA elements responsible for hypoxia-induced
      transcription consist of a short region of the proximal promoter and a <50-bp 3'
      enhancer. The elements act cooperatively to increase the transcriptional
      initiation rate approximately 100-fold in response to low oxygen tension in Hep3B
      cells. Two distinct types of transactivating proteins have been demonstrated to
      bind the response elements in the human EPO enhancer in vitro: one shows hypoxia
      inducible DNA binding activity, while the other activity binds DNA under normoxic
      and hypoxic conditions. We have investigated the DNA-protein interactions on the
      human EPO enhancer in living tissue culture cells that produce EPO in a regulated
      fashion (Hep3B) and in cells that do not express EPO under any conditions tested
      (HeLa). We have identified in vivo DNA-protein interactions on the control
      elements in the human EPO enhancer by ligation-mediated PCR technology. We show
      that the putative protein binding sites in the EPO enhancer are occupied in vivo
      under conditions of normoxia, hypoxia, and cobalt exposure in EPO-producing
      cells. These sites are not occupied in cells that do not produce EPO. We also
      provide evidence for a conformational change in the topography of the EPO
      enhancer in response to hypoxia and cobalt exposure.

PMID- 9001243
TI  - Assessing the pathogenic potential of the V(D)J recombinase by interlocus
      immunoglobulin light-chain gene rearrangement.
AB  - Chromosomal translocations involving antigen receptor genes and oncogenes have
      been observed in several forms of lymphoid malignancy. Observations of their
      lymphocyte-restricted occurrence and a molecular analysis of some translocation
      breakpoints have suggested that some of these rearrangements are generated by
      V(D)J recombinase activity. However, a direct correlation between this activity
      and the generation of such rearrangements has never been established. In
      addition, because these aberrant rearrangements are usually detected only after a
      tumor has been formed, the frequency with which the recombinase machinery
      generates translocations has never been assessed directly. To approach these
      issues, immunoglobulin light-chain gene rearrangements were induced in pre-B
      cells transformed by temperature-sensitive mutants of Abelson murine leukemia
      virus and PCR was used to identify interlocus recombinants. Vlambda Jkappa and
      Vkappa Jlambda rearrangements as well as signal joints resulting from the
      recombination of Vlambda and Jkappa coding elements were recovered and were found
      to be similar in structure to conventional intrachromosomal joints. Because these
      products were detected only when the cells were undergoing active intralocus
      rearrangement, they provide direct evidence that translocations can be generated
      by the V(D)J recombinase machinery. Dilution analyses revealed that interlocus
      rearrangements occur about 1,000 times less frequently than conventional
      intralocus rearrangements. Considering the large numbers of lymphocytes generated
      throughout life, aberrant rearrangements generated by the V(D)J recombinase may
      be relatively common.

PMID- 9001242
TI  - Constitutive activation of Epstein-Barr virus (EBV) nuclear antigen 1 gene
      transcription by IRF1 and IRF2 during restricted EBV latency.
AB  - The Epstein-Barr virus (EBV) EBNA1 gene promoter active in the type I program of
      restricted viral latency was recently identified and shown to reside in the viral
      BamHI Q fragment. This promoter, Qp, is active in a wide variety of cell lines
      and has an architecture reminiscent of eukaryotic housekeeping gene promoters (B.
      C. Schaefer, J. L. Strominger, and S. H. Speck, Proc. Natl. Acad. Sci. USA
      92:10565-10569, 1995; B. C. Schaefer, J. L. Strominger, and S. H. Speck, Mol.
      Cell. Biol. 17:364-377, 1997). Here we demonstrate by deletion analysis that the
      important cis-acting elements regulating Qp are clustered in a relatively small
      region (ca. 80 bp) surrounding the site of transcription initiation. Immediately
      upstream of the site of initiation is a region which is protected from DNase I
      digestion by crude nuclear extracts. Electrophoretic mobility shift analyses
      (EMSA) employing probes spanning this region demonstrated the presence of two
      major protein complexes. Deletion analysis of Qp demonstrated that at least one
      of these complexes plays an important role in Qp activity. Evidence that
      interferon response factor 2 (IRF2) is a major constituent of the most prominent
      EMSA complex and that IRF1 may be a minor component of this complex is presented.
      Transfections into IRF1-/-, IRF2-/-, and IRF1,2-/- fibroblasts demonstrated that
      absence of both IRF1 and IRF2 reduced Qp activity to approximately the same
      extent as mutation of the IRF-binding site in Qp, strongly implicating IRF2, and
      perhaps IRF1, in the regulation of Qp activity. Notably, transcription from Qp
      was not inducible by either alpha or gamma interferon in EBV-negative B cells but
      rather was shown to be constitutively activated by IRF1 and IRF2. This
      observation suggests that IRF1 and IRF2 have a previously unrecognized role as
      constitutive activators of specific genes. Additionally, data presented indicate
      that a protein complex containing the nonhistone architectural protein HMG-I(Y)
      binds to the region identified as the major transcription initiation site for Qp.
      This observation raises the possibility that HMG-I(Y)-induced DNA bending plays a
      role in the initiation of transcription from Qp.

PMID- 9001241
TI  - Nf1-deficient mouse Schwann cells are angiogenic and invasive and can be induced
      to hyperproliferate: reversion of some phenotypes by an inhibitor of farnesyl
      protein transferase.
AB  - We have developed a potential model of Schwann cell tumor formation in
      neurofibromatosis type 1 (NF1). We show that mouse Schwann cells heterozygous or
      null at Nf1 display angiogenic and invasive properties, mimicking the behavior of
      Schwann cells from human neurofibromas. Mutations at Nf1 are insufficient to
      promote Schwann cell hyperplasia. Here we show that Schwann cell hyperplasia can
      be induced by protein kinase A activation in mutant cells. Removal of serum from
      the culture medium also stimulates hyperplasia, but only in some mutant cells.
      After serum removal, clones of hyperproliferating Schwann cells lose contact with
      axons in vitro, develop growth factor-independent proliferation, and exhibit
      decreased expression of the cell differentiation marker P0 protein;
      hyperproliferating cells develop after a 1-week lag in Schwann cells heterozygous
      at Nf1. The experiments suggest that events subsequent to Nf1 mutations are
      required for development of Schwann cell hyperplasia. Finally, an anti-Ras
      farnesyl protein transferase inhibitor greatly diminished both clone formation
      and hyperproliferation of null mutant cells, but not invasion; farnesyl
      transferase inhibitors could be useful in treating benign manifestations of NF1.

PMID- 9001244
TI  - Glucocorticoid receptor-glucocorticoid response element binding stimulates
      nucleosome disruption by the SWI/SNF complex.
AB  - The organization of DNA in chromatin is involved in repressing basal
      transcription of a number of inducible genes. Biochemically defined multiprotein
      complexes such as SWI/SNF (J. Cote, J. Quinn, J. L. Workman, and C. L. Peterson,
      Science 265:53-60, 1994) and nucleosome remodeling factor (T. Tsukiyama and C.
      Wu, Cell 83:1011-1020, 1995) disrupt nucleosomes in vitro and are thus candidates
      for complexes which cause chromatin decondensation during gene induction. In this
      study we show that the glucocorticoid receptor (GR), a hormone-inducible
      transcription factor, stimulates the nucleosome-disrupting activity of the
      SWI/SNF complex partially purified either from HeLa cells or from rat liver
      tissue. This GR-mediated stimulation of SWI/SNF nucleosome disruption depended on
      the presence of a glucocorticoid response element. The in vitro-reconstituted
      nucleosome probes used in these experiments harbored 95 bp of synthetic DNA
      bending sequence in order to rotationally position the DNA. The GR-dependent
      stimulation of SWI/SNF-mediated nucleosome disruption, as evaluated by DNase I
      footprinting, was 2.7- to 3.8-fold for the human SWI/SNF complex and 2.5- to 3.2
      fold for the rat SWI/SNF complex. When nuclear factor 1 (NF1) was used instead of
      GR, there was no stimulation of SWI/SNF activity in the presence of a
      mononucleosome containing an NF1 binding site. On the other hand, the SWI/SNF
      nucleosome disruption activity increased the access of NF1 for its nucleosomal
      binding site. No such effect was seen on binding of GR to its response element.
      Our results suggest that GR, but not NF1, is able to target the nucleosome
      disrupting activity of the SWI/SNF complex.

PMID- 9001245
TI  - C-terminal truncations of the yeast nucleoporin Nup145p produce a rapid
      temperature-conditional mRNA export defect and alterations to nuclear structure.
AB  - A screen for temperature-sensitive mutants of Saccharomyces cerevisiae defective
      in nucleocytoplasmic trafficking of poly(A)+ RNA has identified an allele of the
      NUP145 gene, which encodes an essential nucleoporin. NUP145 was previously
      identified by using a genetic synthetic lethal screen (E. Fabre, W. C. Boelens,
      C. Wimmer, I. W. Mattaj, and E. C. Hurt, Cell 78:275-289, 1994) and by using a
      monoclonal antibody which recognizes the GLFG family of vertebrate and yeast
      nucleoporins (S. R. Wente and G. Blobel, J. Cell Biol. 125:955-969, 1994). Cells
      carrying the new allele, nup145-10, grew at 23 and 30 degrees C but were unable
      to grow at 37 degrees C. Many cells displayed a modest accumulation of poly(A)+
      RNA under permissive growth conditions, and all cells showed dramatic and rapid
      nuclear accumulation of poly(A)+ RNA following a shift to 37 degrees C. The
      mutant allele contains a nonsense codon which truncates the 1,317-amino-acid
      protein to 698 amino acids. This prompted us to examine the role of the carboxyl
      half of Nup145p. Several additional alleles that encode C-terminally truncated
      proteins or proteins containing internal deletions of portions of the carboxyl
      half of Nup145p were constructed. Analysis of these mutants indicates that some
      sequences between amino acids 698 and 1095 are essential for RNA export and for
      growth at 37 degrees C. In these strains, nuclear accumulation of poly(A)+ RNA
      and fragmentation of the nucleolus occurred rapidly following a shift to 37
      degrees C. Constitutive defects in nuclear pore complex distribution and nuclear
      structure were also seen in these strains. Although cells lacking Nup145p grew
      extremely slowly at 23 degrees C and did not grow at 30 degrees C, efficient
      growth at 23 or 30 degrees C occurred as long as cells produced either the amino
      58% or the carboxyl 53% of Nup145p. Strains carrying alleles of NUP145 lacking up
      to 200 amino acids from the carboxy terminus were viable at 37 degrees C but
      displayed nucleolar fragmentation and some nuclear accumulation of poly(A)+ RNA
      following a shift to 37 degrees C. Surprisingly, these strains grew efficiently
      at 37 degrees C in spite of a reduction in the level of synthesis of rRNAs to
      approximately 25% of the wild-type level.

PMID- 9001246
TI  - Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and
      protein kinase A-dependent signals.
AB  - Rheb is a recently described member of the Ras family that was originally
      identified as an immediate-early gene in brain but is also widely expressed in
      other tissues. Here we demonstrate that Rheb interacts with and appears to
      regulate Raf-1 kinase, an essential component of the H-Ras signaling pathway. In
      direct contrast to H-Ras, however, the interaction of Rheb with Raf-1 is
      potentiated by growth factors in combination with agents that increase cyclic AMP
      (cAMP) levels. Protein kinase A-dependent phosphorylation of serine 43 within the
      regulatory domain of Raf-1 reciprocally potentiates its interaction with Rheb and
      decreases its interaction with H-Ras. A single amino acid in the G2 effector
      domain is critical for the differential properties of Rheb. Since Rheb is an
      immediate-early gene, our studies suggest that Rheb functions in concert with H
      Ras to dynamically integrate cAMP and growth factor signaling.

PMID- 9001247
TI  - Role of hydrophobic amino acid clusters in the transactivation activity of the
      human glucocorticoid receptor.
AB  - We have performed a mutagenesis analysis of the 58-amino-acid tau1-core peptide,
      which represents the core transactivation activity of the tau1 transactivation
      domain from the glucocorticoid receptor. Mutants with altered activity were
      identified by phenotypic screening in the yeast Saccharomyces cerevisiae. Most
      mutants with reduced activity had substitutions of hydrophobic amino acids. Most
      single-substitution mutants with reduced activity were localized near the N
      terminus of the tau1-core within a segment that has been shown previously to have
      a propensity for alpha-helix conformation, suggesting that this helical region is
      of predominant importance. The particular importance of hydrophobic residues
      within this region was confirmed by comparing the activities of alanine
      substitutions of the hydrophobic residues in this and two other helical regions.
      The hydrophobic residues were shown to be important for the transactivation
      activity of both the isolated tau1-core and the intact glucocorticoid receptor in
      mammalian cells. Rare mutations in helical regions I and II gave rise to
      increased transcriptional activation activity. These mutations increase the
      hydrophobicity of hydrophobic patches on each of these helices, suggesting a
      relationship between the hydrophobicity of the patches and transactivation
      activity. However, certain nonhydrophobic residues are also important for
      activity. Interestingly, helical region I partially matches a consensus motif
      found in the retinoic acid receptor, VP16, and several other activator proteins.

PMID- 9001248
TI  - Cloning of Caenorhabditis U2AF65: an alternatively spliced RNA containing a novel
      exon.
AB  - The U2 small nuclear ribonucleoprotein particle (snRNP) auxiliary factor, U2AF,
      is an essential splicing factor required for recognition of the polypyrimidine
      tract and subsequent U2 snRNP assembly at the branch point. Because
      Caenorhabditis elegans introns lack both polypyrimidine tract and branch point
      consensus sequences but have a very highly conserved UUUUCAG/R consensus at their
      3' splice sites, we hypothesized that U2AF might serve to recognize this sequence
      and thus promote intron recognition in C. elegans. Here we report the cloning of
      the gene for the large subunit of U2AF, uaf-1. Three classes of cDNA were
      identified. In the most abundant class the open reading frame is similar to that
      for the U2AF65 from mammals and flies. The remaining two classes result from an
      alternative splicing event in which an exon containing an in-frame stop codon is
      inserted near the beginning of the second RNA recognition motif. However, this
      alternative mRNA is apparently not translated. Interestingly, the inserted exon
      contains 10 matches to the 3' splice site consensus. To determine whether this
      feature is conserved, we sequenced uaf-1 from the related nematode Caenorhabditis
      briggsae. It is composed of six exons, including an alternatively spliced third
      exon interrupting the gene at the same location as in C. elegans. uaf-1 is
      contained in an operon with the rab-18 gene in both species. Although the
      alternative exons from the two species are not highly conserved and would not
      encode related polypeptides, the C. briggsae alternative exon has 18 matches to
      the 3' splice site consensus. We hypothesize that the array of 3' splice site
      like sequences in the pre-mRNA and alternatively spliced exon may have a
      regulatory role. The alternatively spliced RNA accumulates at high levels
      following starvation, suggesting that this RNA may represent an adaption for
      reducing U2AF65 levels when pre-mRNA levels are low.

PMID- 9001249
TI  - Ectopic expression of Hel-N1, an RNA-binding protein, increases glucose
      transporter (GLUT1) expression in 3T3-L1 adipocytes.
AB  - 3T3-L1 preadipocytes ectopically expressing the mammalian RNA-binding protein Hel
      N1 expressed up to 10-fold more glucose transporter (GLUT1) protein and exhibited
      elevated rates of basal glucose uptake. Hel-N1 is a member of the ELAV-like
      family of proteins associated with the induction and maintenance of
      differentiation in various species. ELAV proteins are known to bind in vitro to
      short stretches of uridylates in the 3' untranslated regions (3'UTRs) of unstable
      mRNAs encoding growth-regulatory proteins involved in transcription and signal
      transduction. GLUT1 mRNA also contains a large 3'UTR with a U-rich region that
      binds specifically to Hel-N1 in vitro. Analysis of the altered GLUT1 expression
      at the translational and posttranscriptional levels suggested a mechanism
      involving both mRNA stabilization and accelerated formation of translation
      initiation complexes. These findings are consistent with the hypothesis that the
      Hel-N1 family of proteins modulate gene expression at the level of mRNA in the
      cytoplasm.

PMID- 9001250
TI  - AP-1-mediated invasion requires increased expression of the hyaluronan receptor
      CD44.
AB  - Fibroblasts transformed by Fos oncogenes display increased expression of a number
      of genes implicated in tumor cell invasion and metastasis. In contrast to normal
      208F rat fibroblasts, Fos-transformed 208F fibroblasts are growth factor
      independent for invasion. We demonstrate that invasion of v-Fos- or epidermal
      growth factor (EGF)-transformed cells requires AP-1 activity. v-Fos-transformed
      cell invasion is inhibited by c-jun antisense oligonucleotides and by expression
      of a c-jun dominant negative mutant, TAM-67. EGF-induced invasion is inhibited by
      both c-fos and c-jun antisense oligonucleotides. CD44s, the standard form of a
      transmembrane receptor for hyaluronan, is implicated in tumor cell invasion and
      metastasis. We demonstrate that increased expression of CD44 in Fos- and EGF
      transformed cells is dependent upon AP-1. CD44 antisense oligonucleotides reduce
      expression of CD44 in v-Fos- or EGF-transformed cells and inhibit invasion but
      not migration. Expression of a fusion protein between human CD44s and Aequorea
      victoria green fluorescent protein (GFP) in 208F cells complements the inhibition
      of invasion by the rat-specific CD44 antisense oligonucleotide. We further show
      that both v-Fos and EGF transformations result in a concentration of endogenous
      CD44 or exogenous CD44-GFP at the ends of pseudopodial cell extensions. These
      results support the hypothesis that one role of AP-1 in transformation is to
      activate a multigenic invasion program.

PMID- 9001251
TI  - Cleavage of membrane-associated pref-1 generates a soluble inhibitor of adipocyte
      differentiation.
AB  - pref-1 is an epidermal growth factor-like repeat protein present on the surface
      of preadipocytes that functions in the maintenance of the preadipose state. pref
      1 expression is completely abolished during 3T3-L1 adipocyte differentiation.
      Bypassing this downregulation by constitutive expression of full-length
      transmembrane pref-1 in preadipocytes drastically inhibits differentiation. For
      the first time, we show processing of cell-associated pref-1 to generate both a
      soluble pref-1 protein of approximately 50 kDa that corresponds to the ectodomain
      and also smaller products of 24 to 25 kDa and 31 kDa. Furthermore, while all four
      of the alternately spliced forms of pref-1 produce cell-associated protein, only
      the two largest of the four alternately spliced isoforms undergo cleavage in the
      juxtamembrane region to release the soluble 50-kDa ectodomain. We demonstrate
      that addition of Escherichia coli-expressed pref-1 ectodomain to 3T3-L1
      preadipocytes blocks differentiation, thus overriding the adipogenic actions of
      dexamethasone and methylisobutylxanthine. The inhibitory effects of the pref-1
      ectodomain are blocked by preincubation of the protein with pref-1 antibody. That
      the ectodomain alone is sufficient for inhibition demonstrates that transmembrane
      pref-1 can be processed to generate an inhibitory soluble form, thereby greatly
      extending its range of action. Furthermore, we present evidence that alternate
      splicing is the mechanism that governs the production of transmembrane versus
      soluble pref-1, thereby determining the mode of action, juxtacrine or paracrine,
      of the pref-1 protein.

PMID- 9001252
TI  - An alternative splicing event which occurs in mouse pachytene spermatocytes
      generates a form of DNA ligase III with distinct biochemical properties that may
      function in meiotic recombination.
AB  - Three mammalian genes encoding DNA ligases have been identified. However, the
      role of each of these enzymes in mammalian DNA metabolism has not been
      established. In this study, we show that two forms of mammalian DNA ligase III,
      alpha and beta, are produced by a conserved tissue-specific alternative splicing
      mechanism involving exons encoding the C termini of the polypeptides. DNA ligase
      III-alpha cDNA, which encodes a 103-kDa polypeptide, is expressed in all tissues
      and cells, whereas DNA ligase III-beta cDNA, which encodes a 96-kDa polypeptide,
      is expressed only in the testis. During male germ cell differentiation, elevated
      expression of DNA ligase III-beta mRNA is restricted, beginning only in the
      latter stages of meiotic prophase and ending in the round spermatid stage. In 96
      kDa DNA ligase III-beta, the C-terminal 77 amino acids of DNA ligase III-alpha
      are replaced by a different 17- to 18-amino acid sequence. As reported
      previously, the 103-kDa DNA ligase III-alpha interacts with the DNA strand break
      repair protein encoded by the human XRCC1 gene. In contrast, the 96-kDa DNA
      ligase III-beta does not interact with XRCC1, indicating that DNA ligase III-beta
      may play a role in cellular functions distinct from the DNA repair pathways
      involving the DNA ligase III-alpha x XRCC1 complex. The distinct biochemical
      properties of DNA ligase III-beta, in combination with the tissue- and cell-type
      specific expression of DNA ligase III-beta mRNA, suggest that this form of DNA
      ligase III is specifically involved in the completion of homologous recombination
      events that occur during meiotic prophase.

PMID- 9001256
TI  - Sinus surgery: a century of controversy.

PMID- 9001253
TI  - The scs' boundary element: characterization of boundary element-associated
      factors.
AB  - Boundary elements are thought to define the peripheries of chromatin domains and
      to restrict enhancer-promoter interactions to their target genes within their
      domains. We previously characterized a cDNA encoding the BEAF-32A protein (32A),
      which binds with high affinity to the scs' boundary element from the Drosophila
      melanogaster 87A7 hsp70 locus. Here, we report a second protein, BEAF-32B, that
      differs from 32A only in its amino terminus. Unlike 32A, it has the same DNA
      binding specificity as the complete BEAF activity affinity purified from
      Drosophila. We characterize three domains in these proteins. Heterocomplex
      formation is mediated by their identical carboxy-terminal domains, and DNA
      binding is mediated by their unique amino-terminal domains. The identical middle
      domains of 32A and 32B are dispensable for the functions described here, although
      they may be important for boundary element function. 32A and 32B apparently form
      trimers, and the ratio of 32A to 32B varies at different loci on polytene
      chromosomes as judged by immunofluorescence. The scs' element contains a high-
      and low-affinity binding site for BEAF. We observed that interaction with the low
      affinity site is facilitated by binding to the high-affinity site some 200 bp
      distant.

PMID- 9001257
TI  - Ogura and Powers: "Functional restitution of traumatic stenosis of the larynx and
      pharynx." (Laryngoscope 1964;74: 1081-1110).

PMID- 9001258
TI  - Nasal septal surgery 1896-1899: transition and controversy.

PMID- 9001254
TI  - Molecular mechanisms of myogenic coactivation by p300: direct interaction with
      the activation domain of MyoD and with the MADS box of MEF2C.
AB  - By searching for molecules that assist MyoD in converting fibroblasts to muscle
      cells, we have found that p300 and CBP, two related molecules that act as
      transcriptional adapters, coactivate the myogenic basic-helix-loop-helix (bHLH)
      proteins. Coactivation by p300 involves novel physical interactions between p300
      and the amino-terminal activation domain of MyoD. In particular, disruption of
      the FYD domain, a group of three amino acids conserved in the activation domains
      of other myogenic bHLH proteins, drastically diminishes the transactivation
      potential of MyoD and abolishes both p300-mediated coactivation and the physical
      interaction between MyoD and p300. Two domains of p300, at its amino and carboxy
      terminals, independently function to both mediate coactivation and physically
      interact with MyoD. A truncated segment of p300, unable to bind MyoD, acts as a
      dominant negative mutation and abrogates both myogenic conversion and
      transactivation by MyoD, suggesting that endogenous p300 is a required
      coactivator for MyoD function. The p300 dominant negative peptide forms multimers
      with intact p300. p300 and CBP serve as coactivators of another class of
      transcriptional activators critical for myogenesis, myocyte enhancer factor 2
      (MEF2). In fact, transactivation mediated by the MEF2C protein is potentiated by
      the two coactivators, and this phenomenon is associated with the ability of p300
      to interact with the MADS domain of MEF2C. Our results suggest that p300 and CBP
      may positively influence myogenesis by reinforcing the transcriptional
      autoregulatory loop established between the myogenic bHLH and the MEF2 factors.

PMID- 9001255
TI  - Altered replication and inverted repeats induce mismatch repair-independent
      recombination between highly diverged DNAs in yeast.
AB  - Replication, DNA organization, and mismatch repair (MMR) can influence
      recombination. We examined the effects of altered replication due to a mutation
      in the polymerase delta gene, long inverted repeats (LIRs) in motifs similar to
      those in higher eukaryotes, and MMR on intrachromosomal recombination between
      highly diverged (28%) truncated genes in Saccharomyces cerevisiae. A combination
      of altered replication and an LIR increased recombination up to 700-fold, while
      each alone led to a 3- to 20-fold increase. Homeologous recombination was not
      altered by pms1, msh2, and msh3 mismatch repair mutations. Similar to our
      previous observations for replication slippage-mediated deletions, there were >
      or = 5-bp identical runs at the recombination breakpoints. We propose that the
      dramatic increase in recombination results from enhancement of the effects of
      altered replication by the LIR, leading to recombinationally active initiating
      structures. Such interactions predict replication-related, MMR-independent genome
      changes.

PMID- 9001259
TI  - Pediatric aerodigestive foreign body injuries are complications related to
      timeliness of diagnosis.
AB  - Foreign body (FB) injury from aspiration or ingestion is a common pediatric
      health problem. Diagnosis relies on clinical judgment plus medical history,
      physical examination, and radiographic evaluation. A multi-institutional review
      of 1269 FB events revealed that 85% were correctly diagnosed following a single
      physician encounter. However, 15% of the children had an elusive diagnosis (>1
      week), despite previous evaluation. Delays in diagnosis were seven times more
      likely to occur in aspirations than in ingestions. Secondary injuries (e.g.,
      pneumonia and atelectasis) occurred in 13% of airway FBs but in only 1.7% of
      esophageal FBs. Plain radiographs were used in 82% of children, and special
      studies (e.g., fluoroscopy) in only 7%. We conclude that diagnosis of FB injury
      in children is frequently achieved at the initial evaluation but that continued
      surveillance by follow-up visits to health care facilities from parents and other
      caretakers is important, to reduce pulmonary injuries.

PMID- 9001260
TI  - Effectiveness of surgical management of epistaxis at a tertiary care center.
AB  - A retrospective review is presented of 44 consecutive patients requiring
      hospitalization for epistaxis at a tertiary care center. The study had the
      following objectives: 1. to identify predictors of surgical treatment, and 2. to
      compare the effectiveness of different surgical treatments. Length of stay,
      complications, and cost analysis are also presented. Eighteen patients were
      successfully treated nonsurgically, whereas 26 patients received surgical
      treatment. Posterior epistaxis (P<0.05) and an admission hematocrit less than 38%
      (P<0.05) were significant predictors of surgical treatment. The rebleed rate
      after first surgical therapy was 33% for embolization, 33% for endoscopic
      cautery, and 20% for ligation. Since embolization, ligation, and endoscopic
      cautery may have nearly equivalent failure rates, other factors, such as cost and
      institutional expertise, should guide the selection of surgical treatment.

PMID- 9001261
TI  - Virtual endoscopy of the paranasal sinuses using perspective volume rendered
      helical sinus computed tomography.
AB  - Our goal was to use three-dimensional information obtained from helical computed
      tomographic (CT) data to explore and evaluate the nasal cavity, nasopharynx, and
      paranasal sinuses by simulated virtual endoscopy (VE). This was done by utilizing
      a new image reconstruction method known as perspective volume rendering (PVR).
      Thin-section helical CT of the nasal cavity, nasopharynx, and paranasal sinuses
      was performed on a conventional CT scanner. The data were transferred to a
      workstation to create views similar to those seen with endoscopy. Additional
      views not normally accessible by conventional endoscopy were generated. Key
      perspectives were selected, and a video "flight" model was choreographed and
      synthesized through the nasal cavity and sinuses based on the CT data. VE allows
      evaluation of the nasal cavity, nasopharynx, and paranasal sinuses with
      appreciation of the relationships of these spatially complex structures. In
      addition, this technique allows structural visualization with unconventional
      angles, perspectives, and locations not conventionally accessible. Although
      biopsies, cultures, and lavages routinely done with endoscopy cannot be performed
      with VE, this technique holds promise for improving the diagnostic evaluation of
      the nasal cavity, the nasopharynx, and the paranasal sinuses. The unconventional
      visual perspectives and very low morbidity may complement many applications of
      simple diagnostic endoscopy.

PMID- 9001262
TI  - Rehabilitation of patients with extended facial and craniofacial resection.
AB  - Surgery of benign and malignant disease of the nose and sinuses can result in
      disfigurement and disability. Many patients have speech, mastication, and
      swallowing problems, anosmia, and pain. If the orbit is retained, visual loss,
      dystopia, diplopia, and epiphora can occur. This study reviews the senior
      author's experience with 34 patients over the last 18 years. Group and case
      analyses demonstrate that in patients with cancer, the eye can be preserved if
      one anatomical boundary is retained beyond a negative frozen section margin.
      Dystopia can be prevented by reconstruction of the floor with skin and fascial
      grafts or flaps. Epiphora can be reduced by repair of the medial canthus and
      dacryocystorhinostomy. Evidence is presented for prosthetic management of speech
      and swallowing and restoration of cheek contour. Case examples are used to
      illustrate the surgical techniques.

PMID- 9001263
TI  - Extended use of topical nasal decongestants.
AB  - Use of sympathomimetic topical nasal decongestants to treat nasal obstruction is
      usually restricted to 3 to 5 days to avoid potential rebound swelling (rhinitis
      medicamentosa). In this study, 10 healthy volunteers used oxymetazoline (long
      acting topical nasal decongestant) nightly for 4 weeks. Subjects who used
      antihistamines, oral or topical decongestants, or systemic steroids or who had
      active sinusitis were excluded from the study. Weekly history, physical
      examination, and anterior rhinomanometry revealed no adverse effects. Eight (80%)
      subjects developed nightly nasal obstruction a few hours before the evening dose;
      the obstruction resolved within 48 hours if no more decongestant was used. All
      subjects remained responsive to oxymetazoline 4 weeks and 8 weeks after the study
      began. This finding suggests that long-acting decongestants may be safely used
      for longer than the recommended 3 to 5 days without adverse effects if used once
      nightly.

PMID- 9001264
TI  - The effects of 13-cis retinoic acid on squamous cell carcinoma proliferation and
      adhesion to extracellular matrix proteins.
AB  - To understand the role of retinoids in chemoprevention, the authors examined the
      effects of 13-cis retinoic acid (cRA) on squamous cell carcinoma proliferation
      and adhesion to extracellular matrix proteins. The antiproliferative effects of
      cRA were first seen on day 11 (66% inhibition) and progressed through day 19 (96%
      inhibition). Using an adhesion assay, the authors then investigated the effects
      of cRA and transforming growth factor-beta1 (TGF-beta1) on cellular adhesion to
      purified type IV collagen, fibronectin, and laminin matrices. Cells treated for 4
      days with TGF-beta1 increased adhesion by 15% to 29%, and cells treated with cRA
      increased adhesion by 19% to 39%. However, the use of cRA alone resulted in a
      decrease in adhesion when tumor cells were treated for 7 days (20% to 32%) and 15
      days (25% to 40%). The authors also discuss how cRA acts as a differentiating
      agent on squamous cell carcinoma.

PMID- 9001265
TI  - Intratympanic gentamicin for treatment of intractable Meniere's disease: a
      preliminary report.
AB  - Topical administration of aminoglycoside antibiotics in the middle ear can
      achieve "chemical labyrinthectomy" in patients with intractable Meniere's
      disease. Herein we report our results of intratympanic gentamicin therapy in 21
      patients using two different dosing protocols, twice weekly and twice daily
      (b.i.d.). Both hearing and vertigo outcome were evaluated. Complete control of
      episodic vertigo was achieved initially in 20 of 21 patients (95.2%). However, 6
      of 20 responders (30%) developed relapsing symptoms within 12 months. Retreatment
      was successful in 75% of these patients. Overall, hearing was preserved or
      improved in 62% of cases, worse in 24%, and not yet tested in 14%. When the
      cumulative dose of gentamicin was < or = 4 injections in the first week, only 1
      of 14 (7.1%) lost hearing. Intratympanic gentamicin offers better risk/benefit
      outcome than other invasive therapies for intractable Meniere's disease.

PMID- 9001266
TI  - Osteosarcoma of the head and neck: meta-analysis of nonrandomized studies.
AB  - To assess the role of adjuvant therapy in the treatment of osteogenic sarcoma of
      the head and neck, treatment and survival information from 173 patients with
      osteosarcoma of the head and neck was entered into a database. A meta-analysis of
      the data was attempted with primary emphasis on the effect of adjuvant therapy on
      disease outcome. The overall 5-year survival was 37%. Patients with mandibular
      and maxillary tumors had similar survival rates; both groups fared significantly
      better than patients with extragnathic tumors (P<0.001). Treatment with surgery
      alone was associated with significantly longer survival rates (P<0.03) than
      surgery with adjuvant therapy. In the majority of patients reported, information
      about surgical margins was not available. For this reason, the differences may
      not adequately represent the effect of adjuvant therapy. While there have been
      encouraging results with adjuvant treatment protocols for long bone osteosarcoma,
      the ultimate role of radiation and chemotherapy in the management of osteosarcoma
      of the head and neck remains unproven. Nevertheless, we recommend that adjuvant
      therapy be considered due to the poor prognosis in osteosarcoma of the head and
      neck.

PMID- 9001267
TI  - Influence of age on the 'nasal cycle'.
AB  - The nasal cycle is classicially defined as a side-to-side fluctuation in nasal
      engorgement and airflow, with period lengths ranging from approximately 1 to 5
      hours. This cycle, as well as its variants (e.g., cyclic changes on one side of
      the nose only), is produced by alterations in autonomic tone of the nasal
      vasculature and reportedly correlates with a number of ultradian rhythms,
      including asymmetries in left:right cerebral electroencephalographic (EEG)
      activity and differential performance on visual/spatial psychological tasks.
      Since the pacemaker for the nasal cycle is believed to lie within the
      suprachiasmatic nucleus of the hypothalamus, and this nucleus evidences
      degeneration in later life, we sought to determine whether the nasal cycle or its
      variants changes with age. To achieve this end, we used a liquid crystal
      thermography exhalation monitor to measure relative airflow of the two nasal
      chambers at 15-minute intervals for 6 hours in 60 people representing four age
      categories: 18 to 29 years (n=12); 30 to 49 years (n=15); 50 to 69 years (n=13);
      and 70 to 85 years (n=20). Overall, the proportion of subjects exhibiting the
      alternating rhythmicity associated with the classic nasal cycle decreased with
      age. No association was present between nasal cycle parameters and scores on the
      Mini-Mental State Examination (MMSE). The results suggest that the classic nasal
      cycle may be a marker for age-related central nervous system changes.

PMID- 9001269
TI  - Uvulopalatopharyngoplasty versus laser-assisted uvulopalatoplasty for the
      treatment of obstructive sleep apnea.
AB  - Uvulopalatopharyngoplasty (UPPP) was the first surgical procedure specifically
      designed to address the palatal abnormalities seen in many patients with
      obstructive sleep apnea syndrome (OSAS). For adult apneic patients, UPPP remains
      the most commonly performed operation. Beginning in 1993, laser-assisted
      uvulopalatoplasty (LAUP) was introduced for the treatment of snoring and sleep
      apnea. LAUP differs from UPPP because it is performed in the office using only
      local anesthesia, thus being very cost-effective. Seventy-nine patients with OSAS
      underwent surgical treatment: 38 treated with LAUP and 41 with UPPP. The overall
      surgical response rate, defined as a >50% reduction in the postoperative
      respiratory disturbance index (RDI), was achieved in 21 (51.2%) of UPPP-treated
      and 18 (47.4%) of LAUP-treated patients. The RDI decreased from 30.3 +/- 3.7 to
      22.2 +/- 4.4 events/h in the LAUP patients and from 52.1 +/- 5.0 to 25.5 +/- 2.7
      events/h in the UPPP patients. The lowest oxyhemoglobin saturation (LS(aO2))
      increased from 72.8 +/- 2.1 to 80.9 +/- 1.3% in the UPPP patients; there was no
      change in the LAUP patients. Postoperative complications in this series included
      minor bleeding, oral candidiasis, and temporary velopalatal insufficiency in both
      groups. In the carefully selected OSAS patient, LAUP should be considered a
      surgical alternative to UPPP. LAUP may actually be preferable to UPPP in certain
      cases because LAUP is cost-effective, does not require a general anesthetic or
      hospitalization, has very few associated complications, and time lost at work is
      minimal.

PMID- 9001268
TI  - Otolaryngologic manifestations of sarcoidosis: presentation and diagnosis.
AB  - Neuro-otologic manifestations of sarcoidosis are rare. Dizziness in particular is
      a rare presenting complaint of the patient afflicted with this systemic
      granulomatous disorder. Head and neck and sinonasal presentations of this disease
      are more common. We reviewed our experience with six such patients who presented
      for management of their otolaryngologic (ORL) manifestations in order to
      delineate the involvement of the otolaryngologist in the treatment and diagnosis
      of these patients, with a focus upon the relevant tests and procedures in the
      otolaryngologist's de novo diagnosis of sarcoidosis. Studies ordered in the
      course of otolaryngologic evaluation and their utility in the diagnosis of
      sarcoidosis by the otolaryngologist are reviewed and classified into useful,
      supportive, and ancillary. The otolaryngologist played an important role in
      diagnosis, with four of six patients diagnosed to have sarcoidosis on the basis
      of their otolaryngologic presentations. Biopsy was performed by the
      otolaryngologist for diagnosis of sarcoidosis in all four of these cases.
      Steroids were central to treatment. Oral steroid therapy was the principal
      treatment: both patients with neuro-otologic sarcoid were successfully managed
      with oral steroids. Intralesional steroids were necessary to treat the skin
      lesion. One of six patients patients experienced complications related to steroid
      use.

PMID- 9001270
TI  - Low-dose intratympanic gentamicin and the treatment of Meniere's disease:
      preliminary results.
AB  - The most disabling symptom for most patients with unilateral Meniere's disease is
      vertigo. Eradication of the diseased end organ is effective in eliminating the
      vertigo. Labyrinthectomy remains the "gold standard"; unfortunately, residual
      hearing is sacrificed to obtain this end. The purpose of this study is to
      evaluate low-dose intratympanic gentamicin for the control of vertigo and for the
      preservation of hearing. A single dose of gentamicin (10-80 mg) was injected into
      the middle ear space of 23 patients with unilateral Meniere's disease as an
      office procedure. Eighty-four percent of the patients had no episodes of vertigo
      during the last 6 months of follow-up. Pure tone average and word discrimination
      scores were unchanged as a group. Ninety-five percent of patients had a hearing
      loss at 6 and 8 kHz that averaged 7.5 dB. Caloric function was reduced in 93%.
      Low-dose intratympanic gentamicin is a safe, simple, office procedure that is
      effective in controlling the definitive vertiginous episodes in most patients
      with unilateral Meniere's disease. Control of vertigo can be obtained with
      preservation of hearing.

PMID- 9001271
TI  - Particulate matter in the posterior semicircular canal.
AB  - The pathoetiology of benign paroxysmal positional vertigo (BPPV) is
      controversial. Particulate matter within the posterior semicircular canal has
      been identified intraoperatively in patients with BPPV but has also been reported
      in non-BPPV patients at the time of translabyrinthine surgery (Parnes LS, McClure
      JA. Free-floating endolymphatic particles: a new operative finding during
      posterior semicircular canal occlusion. Laryngoscope 1992;102:988-92; Schuknecht
      HF, Ruby RRF. Cupulolithiasis. Adv Otorhinolaryngol 1973;20: 434-43; Kveton JF,
      Kashgarian M. Particulate matter within the membranous labyrinth: pathologic or
      normal? Am J Otol 1994;15:173-6). The nature of the particulate matter remains
      unknown. The purpose of this study was to prospectively examine the posterior
      semicircular canal of patients with and without a clinical history of BPPV for
      the presence of particulate matter. Seventy-three patients without BPPV symptoms
      undergoing labyrinthine surgery (vestibular schwannoma excision or
      labyrinthectomy) and 26 patients with BPPV undergoing the posterior semicircular
      canal occlusion procedure were compared. Additionally, 70 archived temporal bones
      without a history of BPPV were examined microscopically for the presence of
      particulate matter within the lumen of the membranous labyrinth. No particles
      were observed intraoperatively in any of the 73 patients without a history of
      BPPV. Particulate matter was observed in 8 of 26 patients at the time of the
      posterior semicircular canal occlusion procedure for intractable BPPV. Of the 70
      temporal bones examined, 31 did not show significant postmortem changes and also
      did not demonstrate cupulolithiasis or canalithiasis. Particulate matter from
      within the membranous posterior semicircular canal was removed from one patient
      at the time of posterior semicircular canal occlusion for intractable BPPV
      symptoms and was examined by scanning electron microscopy. The particulate matter
      appeared morphologically consistent with degenerating otoconia. These data show a
      statistically significant association between the presence of particles within
      the posterior semicircular canal in this study and the symptom complex of BPPV.

PMID- 9001273
TI  - Restoration of function in the paralyzed rabbit orbicularis oculi muscle by
      direct functional electrical stimulation.
AB  - Restoration of the ability to blink and protect the eye in the patient with
      facial paralysis remains a challenge. Although many treatments exist, no one
      approach corrects all the deficits associated with the loss of orbicularis oculi
      function. In this study, the author investigated the feasibility of restoring
      function by direct electrical stimulation of the paralyzed orbicularis oculi
      muscle in the rabbit model. Using a pacing device developed by the author,
      functional restoration of a normal-appearing blink was produced throughout 30
      days of continuous pacing in six rabbits with transected facial nerves.
      Histologic evaluations of the paced tissues demonstrated no evidence of
      detrimental effects attributable to the electrical stimulation. The findings of
      this study support the feasibility of employing direct electrical stimulation to
      restore the function of paralyzed orbicularis oculi muscles. Potential
      applications may also exist in other areas in which peripheral denervation
      creates functional impairment.

PMID- 9001272
TI  - Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in
      Hashimoto's thyroiditis.
AB  - Hashimoto's thyroiditis is an inflammatory disease of the thyroid gland with
      autoimmune etiology. Patients afflicted with Hashimoto's have a higher risk of
      thyroid malignancies such as papillary thyroid carcinoma. In the present study,
      we investigated the frequency of papillary thyroid carcinoma specific genes in
      patients diagnosed with Hashimoto's disease. The newly identified oncogenes
      RET/PTC1 and RET/PTC3 provide useful and specific markers of the early stages of
      papillary carcinoma as they are highly specific for malignant cells. Using a
      sensitive and specific reverse transcriptase-polymerase chain reaction (RT-PCR)
      assay, we found messenger RNA (mRNA) expression for the RET/PTC1 and RET/PTC3
      oncogenes in 95% of the Hashimoto's patients studied. All Hashimoto's patients
      presenting without histopathologic evidence of papillary thyroid cancer showed
      molecular genetic evidence of cancer. These data suggest that multiple,
      independent occult tumors exist in these patients at high frequency.

PMID- 9001274
TI  - Functional endoscopic sinus surgery and 109 mycetomas of paranasal sinuses.
AB  - Mycetomas of paranasal sinuses are more frequently diagnosed with the widespread
      use of nasal endoscopy and computed tomography (CT). We present a series of 109
      cases treated by functional endoscopic sinus surgery (FESS) with a mean follow-up
      of 29 months. All localizations were seen, and contrary to what was initially
      thought, seven cases presented in multiple sites. Several clinical presentations
      were found, from a pansinusal involvement to a simple mycetoma hanging in a
      superior meatus. A heterogeneous sinus opacity with microcalcifications on CT
      scan is very suggestive of the diagnosis, but a homogeneous opacity may be
      encountered even with bone lysis. FESS was performed in all cases to obtain a
      wide opening of the affected sinuses, permitting a careful extraction of all
      fungal material. In the postoperative period, no medical treatment is prescribed.
      With a mean follow-up of 29 months, only four recurrences were seen. This study
      reinforces the interest in FESS for cases of mycetoma of the paranasal sinuses.

PMID- 9001275
TI  - Use of the KTP-532 laser in acoustic neuroma surgery.
AB  - The potassium titanyl phosphate (KTP-532) laser has been applied to otologic
      surgery with a proven record of both safety and efficacy. The aim of this study
      was to demonstrate the use, safety, and advantages of laser dissection in the
      surgical treatment of acoustic neuromas. The authors' experience with 111
      patients in whom laser surgery was used in acoustic neuroma is presented, with
      emphasis on surgical technique employed and facial nerve functional outcome. The
      method of laser dissection did not result in deleterious neurologic sequelae or
      laser-specific complications. In addition, laser dissection afforded certain
      advantages to traditional techniques, especially in larger tumors. The facial
      nerve functional outcome as assessed by the House-Brackmann grading system
      revealed that 90.2% of small tumors, 72.2% of medium tumors, and 75.0% of large
      tumors achieved satisfactory (grades I and II) functional results. These results
      compare favorably with the literature describing nonlaser dissection techniques.
      The observations and results reported in this article demonstrate the safety of
      the KTP-532 laser in the posterior cranial fossa, and specific advantages that
      this technology may offer to the surgical armamentarium of the neuro-otologist
      are outlined.

PMID- 9001276
TI  - Liquid household bleach ingestion in children: a retrospective review.
AB  - Current literature and some standard reference textbooks fail to adequately
      delineate the management of liquid household bleach (sodium hypochlorite) as
      different from other caustic agents. A literature review and retrospective study
      were conducted to focus attention on the clinical course and the low potential
      for development of long-term sequelae secondary to liquid household bleach
      ingestion in children. The records of 19 patients were reviewed. The mean age of
      children ingesting bleach was 24 months. Most children obtained the liquid from
      an open container such as a cup. There were no short- or long-term sequelae. We
      introduce an algorithm for the management of accidental ingestion of liquid
      household bleach in children. We conclude that in the United States accidental
      bleach ingestion in children is usually associated with a benign clinical course
      and usually does not require hospitalization, corticosteroids, or antibiotics
      unless there is severe dysphagia or signs of significant injury. Esophagoscopy
      may not be necessary, but fiberoptic examination of the pharynx and larynx should
      be included in the assessment of these children.

PMID- 9001277
TI  - Major patterns of laryngeal electromyography and their clinical application.
AB  - Laryngeal electromyography (LEMG) is clinically valuable in the evaluation of
      laryngeal dysfunction and vocal fold immobility. To facilitate clinical
      application of this electrophysiologic test, a detailed description of modified
      LEMG techniques is presented. The techniques were applied for simultaneous
      bilateral recordings of the thyroarytenoid, cricothyroid, and posterior
      cricoarytenoid muscles. The basic patterns of LEMG are classified into three
      different types: normal, neuropathy, and myopathy. In an attempt to characterize
      these patterns, we have reported eight LEMG-documented cases: unilateral
      laryngeal paralysis, bilateral laryngeal paralysis, cricoarytenoid joint
      dislocation, cricoarytenoid joint ankylosis, laryngeal myopathy, pharyngeal
      paralysis (soft palate paralysis), spasmodic dysphonia, and unilateral laryngeal
      paralysis with anastomosis. The significance of the major LEMG patterns is
      discussed.

PMID- 9001278
TI  - Intraotic administration of gentamicin: a new method to study ototoxicity in the
      crista ampullaris of the bullfrog.
AB  - A new method of local gentamicin administration was tested in the bullfrog inner
      ear to achieve ototoxic-induced hair cell destruction. Gelfoam pledgets soaked
      with known amounts of gentamicin were inserted into the perilymphatic cisterna of
      the bullfrog through a ventral surgical approach. A dose of 1.20 mg gentamicin,
      consistent with a perilymphatic concentration of 65 microg/ml, resulted in the
      desired ototoxic-induced hair cell damage, that is, complete hair cell
      destruction with minimal disruption of other components of the sensory
      epithelium. This study demonstrates that this is a useful and simple method to
      investigate the process of vestibular ototoxicity and hair cell regeneration,
      including aspects of hair cell destruction and repair.

PMID- 9001279
TI  - Managing death and dying in the intensive care unit.

PMID- 9001280
TI  - Ethical considerations in pulmonary genetic testing and gene therapy.

PMID- 9001281
TI  - Population and occupational screening for obstructive sleep apnea: are we there
      yet?
AB  - Several features of obstructive sleep apnea (OSA) suggest that it may be an
      appropriate disease for screening programs for general populations and more
      specific high-risk groups. Preliminary data suggest that OSA represents an
      important health problem in terms of high prevalence, increased levels of
      morbidity and mortality, and increased public safety risk. Furthermore, the
      chronicity of the disease and the relatively low levels of recognition of the
      disorder in the medical community suggest a potential for lead-time gains for
      screening programs. Specific groups that might be considered for screening
      programs include commercial vehicle operators, hazardous duty personnel, and
      certain groups of medical patients. The purpose of this clinical commentary is to
      consider the issues of population and specific group screening for OSA by
      reviewing the general principles of screening for chronic disease and then
      applying these principles specifically in the case of OSA. More extensive
      outcomes data relating levels of severity of the disorder to its potential
      adverse outcomes are needed and will assist in tailoring appropriate screening
      programs and determining the cost-effectiveness of screening various populations.

PMID- 9001282
TI  - Increasing incidence of withholding and withdrawal of life support from the
      critically ill.
AB  - To determine whether limits to life-sustaining care are becoming more common, we
      attempted to quantify the incidence of recommendations to withhold or withdraw
      life support from critically ill patients, to describe how patients respond to
      these recommendations, and to examine how conflicts over these recommendations
      are resolved. In 1992 and 1993 we prospectively enrolled 179 consecutive patients
      from two intensive care units (ICUs) for whom a recommendation was made to
      withhold or withdraw life support. Where possible, we compared results with data
      collected in the same units over a similar time period in 1987 and 1988.
      Recommendations to withhold or withdraw life support preceded 179 of 200 deaths
      (90%) in 1992 and 1993, compared with 114 of 224 deaths (51%) in 1987 and 1988
      (chi2 = 73.76, p < 0.001]. Cardiopulmonary resuscitation was initiated in 10% of
      deaths in 1992 and 1993 as compared with 49% in 1987 and 1988. Ninety percent of
      patients agreed within less than 5 d, and only eight patients (4%) refused
      physicians' recommendations to limit life support. In cases of conflict,
      physicians in 1992 and 1993 deferred to patients with one exception: physicians
      were willing to refuse surrogate requests for resuscitation of patients they
      considered hopelessly ill. We conclude that 90% of patients who die in these ICUs
      now do so following a decision to limit therapy, that this represents a major
      change in practice in these institutions over a period of 5 yr, that most
      patients and surrogates accept an appropriate recommendation to withhold or
      withdraw life support, and that physicians will refuse surrogate requests in
      certain circumstances.

PMID- 9001283
TI  - Serum ferritin as a predictor of the acute respiratory distress syndrome.
AB  - We investigated serum ferritin levels as a predictor of the acute respiratory
      distress syndrome (ARDS) because: (1) proinflammatory cytokines, which are
      implicated in ARDS, increase ferritin synthesis; and (2) oxidative stress in
      patients at risk for ARDS might liberate iron from ferritin, accelerating toxic
      hydroxyl radical (.OH) formation. Serum ferritin levels measured by
      radioimmunoassay (RIA) were greater in 75 patients at risk for ARDS (women, p <
      0.0001; men, p < 0.0001) and 8 patients with ARDS (women, p = 0.001; men, p =
      0.0009) than in healthy control subjects. Serum ferritin levels were also greater
      in female (p = 0.003) and male (p = 0.003) at-risk patients who developed ARDS
      than in patients who did not develop ARDS. In women, a value exceeding 270 ng/ml
      predicted ARDS with an 83% sensitivity, 71% specificity, 67% positive, and 86%
      negative predictive value. In men, a value exceeding 680 ng/ml predicted ARDS
      with a 60% sensitivity, 90% specificity, 75% positive, and 82% negative
      predictive value. Serum ferritin levels did not correlate with C-reactive protein
      levels, were not different in medical or surgical at-risk patients, and were not
      accounted for by liver disease. Evaluating serum ferritin levels in at-risk
      patients may help predict the development of ARDS and thereby improve study and
      treatment of ARDS. Elevated serum ferritin levels may also regulate the
      participation of iron in the oxidative responses that contribute to ARDS.

PMID- 9001284
TI  - Noninvasive monitoring of cardiac output in critically ill patients with
      thoracocardiography.
AB  - Thoracocardiography noninvasively estimates changes in cardiac output by
      recording ventricular volume curves from an inductive plethysmographic transducer
      placed around the chest near the xiphoid process. We evaluated performance of
      thoracocardiography for estimation of cardiac output in 21 critically ill
      patients in comparison to thermodilution. A total of 201 paired cardiac output
      measurements were obtained over periods of 35 to 254 min. Since
      thoracocardiography tracks relative changes in cardiac output but does not
      provide absolute values, the first cardiac output by thermodilution in each
      patient was used to calibrate thoracocardiography for comparisons of subsequent
      cardiac output estimates to thermodilution. The mean difference (bias) of cardiac
      output (thoracocardiography - thermodilution) was 0.0 L/min, the limits of
      agreement (bias +/- 2 SD) included a range from -1.5 to +1.6 L/min. For
      estimations of relative changes in cardiac output by thoracocardiography and
      thermodilution the bias was 0%, and the limits of agreement -21 and +22%. We
      conclude that thoracocardiography is a promising noninvasive technique for
      monitoring cardiac output in critically ill patients.

PMID- 9001285
TI  - Systemic, pulmonary and mesenteric perfusion and oxygenation effects of dopamine
      and epinephrine.
AB  - The response of the systemic, pulmonary, hepatic and portal circulations to
      infusion of dopamine and epinephrine was studied in newborn piglets 1 to 3 d of
      age. Anesthetized animals were instrumented to measure cardiac index (CI),
      hepatic arterial flow, and portal venous blood flow. Catheters were inserted for
      measurement of systemic arterial pressure (SAP), pulmonary arterial pressure
      (PAP), and for sampling of arterial, portal venous, and mixed venous oxygen
      saturations and plasma lactate levels. Systemic, pulmonary and mesenteric
      vascular resistance indices (SVRI, PVRI, MVRI), and systemic and mesenteric
      oxygen extraction were calculated. Dopamine and epinephrine were infused in doses
      of 2, 10, 32 microg/kg/min and 0.2, 1.0, 3.2 microg/kg/min respectively, given in
      random order. Significant increases in SAP, PAP, and CI were demonstrated with 32
      microg/kg/min of dopamine and the two higher doses (1.0 and 3.2 microg/kg/min) of
      epinephrine. There were no significant changes in SVRI and PVRI with dopamine
      infusions. Epinephrine at 3.2 microg/kg/min significantly elevated SVRI and PVRI.
      The SAP/PAP ratio was decreased with 32 microg/kg/min of dopamine whereas
      epinephrine did not affect the ratio. Dopamine had no significant effect on
      hepatic arterial flow, portal venous flow, or mesenteric vascular resistance.
      Epinephrine infusion at 3.2 microg/kg/min decreased portal venous blood flow,
      total hepatic blood flow, and hepatic oxygen delivery with an increase in
      calculated mesenteric vascular resistance. Systemic and mesenteric oxygen
      extraction were not affected by dopamine or epinephrine infusions. Plasma lactate
      levels were significantly elevated with epinephrine infusion 3.2 microg/kg/min.
      The differential responses of dopamine and epinephrine on pulmonary and
      mesenteric circulations may be significant in the pathophysiology and management
      of persistent fetal circulation and necrotizing enterocolitis.

PMID- 9001286
TI  - Neutrophil rheologic changes in septic shock.
AB  - Decreases in effective capillary blood flow during septic shock may be related to
      changes in neutrophil rheology which contribute to microvascular occlusion. The
      purpose of this study was to examine neutrophil deformability, adherence, and
      aggregation in patients with severe sepsis and septic shock. Neutrophils were
      isolated from six patients with septic shock (SS), 12 patients with severe sepsis
      (S), six noninfected critically ill patients (CINS), and nine normal volunteers
      (N). Neutrophil deformability was determined by examining filtration through 5
      microm filters. Neutrophil aggregation was measured by aggregometry and leukergy.
      Neutrophil adherence was examined by assessing the binding of latex beads to
      neutrophils. Patients with S and SS demonstrated decreased neutrophil
      filterability of 27 +/- 2% and 16 +/- 5%, respectively (p < 0.01), in comparison
      with N subjects, 55 +/- 4% and CINS patients, 58 +/- 2%. Preincubation of
      neutrophils from S and SS patients with cytochalasin D significantly increased
      the percent filtration of neutrophils. Neutrophil aggregation, measured by
      aggregometry, was increased in SS patients, 16 +/- 4% (p < 0.01) compared with N
      subjects, 1 +/- 0.2% and CINS patients, 1 +/- 0.2%. Incubation of neutrophils of
      SS patients with anti-CD11/CD18 significantly increased the filtration of
      isolated neutrophils to 46 +/- 3% (p < 0.01) and decreased aggregation to 7 +/-
      2%. Neutrophil adherence was not increased in S or SS patients. These
      observations suggest that neutrophil deformability is decreased in patients with
      S and SS. Increased leukoaggregation may also contribute to decreased
      filterability of neutrophils in SS patients. These mechanisms may play a role in
      impaired microvascular flow in septic shock.

PMID- 9001287
TI  - Higher concentrations of matrix metalloproteinases in bronchoalveolar lavage
      fluid of patients with adult respiratory distress syndrome.
AB  - This study was designed to investigate possible involvement of type IV
      collagenolytic matrix metalloproteinases (MMPs; 72-kDa type IV collagenase [MMP
      2], 92-kDa type IV collagenase [MMP-9]), and the respective specific tissue
      inhibitors of these MMPs (TIMP-2 and TIMP-1) in the development of adult
      respiratory distress syndrome (ARDS). We determined the concentrations of these
      enzymes in the bronchoalveolar lavage fluid (BALF) from patients with ARDS using
      newly developed sensitive one-step sandwich enzyme immunoassay methods. BALF
      obtained from the 17 patients and eight healthy volunteer control subjects were
      also used for the analysis of the number of the cellular component.
      Concentrations of the 7S portion of type IV collagen and laminin in the BALF were
      measured as markers of basement membrane disruption. In the BALF from the ARDS
      patients, the concentrations of MMP-2 (66.7 +/- 57.0 ng/ml versus < 7.0 ng/ml for
      controls, p < 0.01) and MMP-9 (118.0 +/- 309.3 ng/ml versus 9.0 +/- 9.5 ng/ml for
      controls, p < 0.05), and the specific inhibitor of MMP-9 (TIMP-1) (161.0 +/-
      145.0 ng/ml versus < 50 ng/ml for controls, p < 0.01) were significantly higher
      compared with those for healthy control subjects. In the ARDS patients, the
      concentrations of MMP-2 correlated both with those of 7S collagen and laminin;
      MMP-9 with the concentration of 7S collagen and the number of neutrophils. These
      findings suggest that the increased concentration of collagenolytic MMPs in lung
      plays a role in the pathogenesis of ARDS.

PMID- 9001288
TI  - Modulation of human endothelial thrombomodulin by neutrophils and their release
      products.
AB  - Pulmonary microvascular injury, one of the earliest events in adult respiratory
      distress syndrome (ARDS), is caused by the release of injurious products from
      stimulated neutrophils and other inflammatory cells in the lung microvessels. An
      increased level of the endothelial cell-surface anticoagulant protein
      thrombomodulin (TM) in plasma from patients with ARDS as shown in this study may
      be one consequence of this, and our objective in this investigation was to define
      the mechanisms by which TM is modulated by neutrophils, using an endothelial
      tissue culture system. Human neutrophils in contact with endothelium caused a
      fourfold reduction in cell-surface TM activity, but only after prior neutrophil
      priming and activation. Neutrophil release products elastase and cathepsin G
      caused rapid dose-related reductions in endothelial cell-surface TM activity,
      with complete abolition at 5 microg/ml in the absence of endothelial detachment.
      H2O2 also reduced TM activity. TM antigen accumulated in culture supernatant
      after treatment of endothelium with cathepsin G, indicating proteolytic release
      of cell-surface TM. We conclude that primed activated neutrophils are potent
      modulators of endothelial TM in vitro.

PMID- 9001290
TI  - Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary
      Complications of HIV Infection Study Group.
AB  - The Pulmonary Complications of HIV Infection Study is a prospective, multicenter,
      observational study evaluating pulmonary disease among HIV-infected persons. For
      approximately 52 mo, 1,182 HIV-infected subjects were followed. All participants
      were evaluated for pulmonary disease on a predetermined schedule. There were 145
      episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with
      risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/microl and 95% had CD4
      counts less than 200/microl. Subtle changes in diffusing capacity for carbon
      monoxide (DLCO) were associated with PCP. Univariate analysis identified
      recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and
      unintentional weight loss to be associated with risk among persons with CD4
      counts above 200/microl. Subjects in whom CD4 counts declined to below 200/microl
      and who were not receiving preventive therapy were nine times more likely to
      develop PCP within 6 mo compared with subjects who received such therapy. A
      strong trend toward differences between the sexes was detected. Black subjects
      had less than one third the risk of developing PCP as did white subjects (p <
      0.0001). There was no significant difference in risk by HIV transmission
      category, study site, frequency of follow-up, age, education, smoking history, or
      use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte
      count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p <
      0.0001), and declining DLCO (p = 0.015) to influence risk. Constitutional signs
      and symptoms indicate increased risk for PCP among HIV-infected persons with CD4
      counts above 200/microl.

PMID- 9001289
TI  - The regional production of cytokines and lactate in sepsis-related multiple organ
      failure.
AB  - In order to explore whether an organ-specific pattern in cytokine and lactate
      concentrations exists in patients with multiple organ failure (MOF), we measured
      the cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha
      (TNF-alpha), and lactate in blood taken from the hepatic vein, pulmonary
      capillaries, and peripheral veins of 10 patients with MOF with hepatic
      involvement (MOF-HI), eight patients with MOF and adult respiratory distress
      syndrome (MOF-ARDS), and five head-injured patients (controls). Ten additional
      patients participated in a study of arteriovenous pulmonary concentration
      gradients of these substances. For statistical analysis, nonparametric tests and
      analysis of variance (ANOVA) were used. The regional concentrations of these
      substances exhibited a different pattern in the two MOF groups. In the MOF-HI
      group, mean +/- SD cytokines IL-1beta and IL-6 (pg/ml) were respectively 216 +/-
      100 and 461 +/- 343 in the hepatic sinusoidal blood; 149 +/- 52 and 293 +/- 204
      in pulmonary capillary blood; and 148 +/- 105 and 234 +/- 162 in peripheral
      venous blood. In the MOF-ARDS group the corresponding levels were 180 +/- 103 and
      235 +/- 124; 235 +/- 94 and 280 +/- 108; and 130 +/- 77 and 194 +/- 127. The TNF
      alpha levels also exhibited the same pattern. The mean +/- SD corresponding
      levels (mmol/L) for lactate in the MOF-HI group were 3.1 +/- 1.8, 1.5 +/- 0.3,
      and 1.2 +/- 0.6, and in the MOF-ARDS group were 1.1 +/- 0.9, 1.8 +/- 1.1, and 1.0
      +/- 0.2, respectively. The differences in the levels of all substances between
      the liver and lungs in the two MOF groups were statistically significant (p <
      0.003). In the study of transpulmonary gradients it was shown that the levels of
      cytokine and lactate were lower in arterial blood than in mixed venous blood in
      MOF-HI patients, whereas the opposite was true in MOF-ARDS patients. In this
      study, we found that in MOF, cytokines and lactate are secreted from the most
      severely affected organs.

PMID- 9001291
TI  - Intensive care of patients with HIV infection: utilization, critical illnesses,
      and outcomes. Pulmonary Complications of HIV Infection Study Group.
AB  - To examine intensive care unit (ICU) admission rates and diagnoses of patients
      with HIV infection, and to determine the outcomes of different critical
      illnesses, we analyzed data derived from the 63 patients who were admitted to an
      ICU from among the 1,130 adults with HIV infection who did not have AIDS at the
      time of enrollment in a multicenter prospective study. Patients were admitted and
      treated according to the judgment of their physicians. During 4,298 patient-years
      of follow-up for the entire cohort, there were 1,320 hospital admissions, of
      which 68 (5%) included admission to an ICU. Twenty-five (40%) of the patients
      admitted to the ICU died during that admission. Twenty-four patients (38%) were
      admitted with a principal diagnosis of lung disease; 11 had Pneumocystis carinii
      pneumonia (PCP), one of whom was coinfected with Aspergillus fumigatus and
      Legionella pneumophilia, and six of them (55%) died. Four had bacterial
      pneumonia, two had pulmonary edema caused by renal failure, and one each had
      pulmonary tuberculosis, pulmonary Kaposi's sarcoma, pneumothorax, adult
      respiratory distress syndrome, severe pulmonary fibrosis, cytomegalovirus
      pneumonitis, and metastatic adenocarcinoma to the lungs. Eleven of these 14
      patients (79%) died. Thirty-nine patients had 44 admissions for nonpulmonary
      diagnoses, including gastrointestinal disorders (14 admissions), cardiovascular
      disorders (nine), sepsis syndrome (six), neurologic disorders (four), monitoring
      and ICU nursing care during or after a procedure (four), metabolic disorders
      (three), trauma (two), drug overdose (one), and unknown reasons (one). Nine (23%)
      of these patients died. Twenty-eight patients underwent mechanical ventilation,
      and 16 (57%) died. Seven (25%) had PCP (five died), seven had other primary
      pulmonary diseases (six died), and 14 were placed on mechanical ventilation for
      nonpulmonary disorders (five died). Survival did not correlate with CD4 count
      determined within 6 mo of admission to the ICU. In conclusion, the range of
      indications for critical care in patients with HIV infection is diverse. PCP
      accounted for only 16% of the ICU admissions, and mechanical ventilation for PCP
      and other pulmonary disorders was associated with a high mortality rate. In
      contrast, mechanical ventilation for nonpulmonary disorders, and admission to the
      ICU for nonpulmonary diagnoses was associated with a more favorable outcome.

PMID- 9001293
TI  - Two-step tuberculin skin testing in HIV-infected persons in Uganda.
AB  - Identifying persons infected with both human immunodeficiency virus (HIV) and
      Mycobacterium tuberculosis (MTB) is often difficult because of the reduced
      sensitivity of tuberculin skin testing in HIV-infected persons. To determine the
      value of two-step tuberculin skin testing (TTST) as a method of increasing the
      sensitivity of tuberculin skin testing in HIV-infected persons, a consecutive
      sample of 58 HIV-infected persons being screened for a TB preventive therapy
      trial in Uganda with an initial purified protein derivative (PPD) response < 5 mm
      completed two-step tuberculin and candida skin testing. The mean change in PPD
      size between the two tests, placed a mean of 8 d apart, was +2.1 mm (SD 4.4 mm,
      range -4 to +16 mm). Seventeen subjects (29%) had a boosted response (PPD1 < 5
      and PPD2 > or = 5). In a multiple logistic regression model, boosted responses
      were independently associated with a CD4 count between 200 and 500 microl(-1) (p
      = 0.02) and a higher body mass index (p = 0.05). TTST may be valuable in
      identifying MTB infection and in preventing misclassification of boosted
      responses as skin test conversions in HIV-infected persons, especially persons
      with CD4 counts between 200 and 500 microl(-1) from areas with a high prevalence
      of MTB infection or from areas with a low prevalence of MTB infection who have
      other risk factors for MTB infection.

PMID- 9001292
TI  - Respiratory disease trends in the Pulmonary Complications of HIV Infection Study
      cohort. Pulmonary Complications of HIV Infection Study Group.
AB  - We examined trends in the incidence of specific respiratory disorders in a
      multicenter cohort with progressive human immunodeficiency virus (HIV) disease
      during a 5-yr period. Individuals with a wide range of HIV disease severity
      belonging to three transmission categories were evaluated at regular intervals
      and for episodic respiratory symptoms using standard diagnostic algorithms.
      Yearly incidence rates of respiratory diagnoses were assessed in the cohort as a
      whole and according to CD4 count or HIV transmission category. The most frequent
      respiratory disorders were upper respiratory tract infections, but the incidence
      of lower respiratory tract infections increased as CD4 counts declined. Specific
      lower respiratory infections followed distinctive patterns according to study
      entry CD4 count and transmission category. Acute bronchitis was the predominant
      lower respiratory infection of cohort members with entry CD4 counts > or = 200
      cells/mm3. In cohort members with entry CD4 counts of 200 to 499 cells/mm3, the
      incidence of bacterial and Pneumocystis carinii pneumonia each increased an
      average of 40% per year. In members with entry CD4 counts < 200 cells/mm3, acute
      bronchitis, bacterial pneumonia, and P. carinii pneumonia occurred at high rates
      without discernible time trends, despite chemoprophylaxis in more than 80% after
      Year 1, and the rate of other pulmonary opportunistic infections increased over
      time. Each year, injecting drug users had a higher incidence of bacterial
      pneumonia than did homosexual men. The yearly rate of tuberculosis was < 3
      episodes/100 person-yr in each entry CD4 and HIV-transmission group. We conclude
      that the time trends of HIV-associated respiratory disorders are determined by
      HIV disease stage and influenced by transmission category. Whereas acute
      bronchitis is prevalent during all stages of HIV infection, incidence rates of
      bacterial pneumonia and P. carinii pneumonia rise continuously during progression
      to advanced disease. In advanced disease, the incidence of acute bronchitis,
      bacterial pneumonia and P. carinii pneumonia is high despite widespread
      chemoprophylaxis.

PMID- 9001294
TI  - Allergen exposure decreases glucocorticoid receptor binding affinity and steroid
      responsiveness in atopic asthmatics.
AB  - Allergen exposure can confound the management of asthma. To understand the
      potential mechanisms by which allergens increase the steroid requirements in
      atopic asthmatics, we examined the effects of allergens on glucocorticoid
      receptor (GCR) binding affinity and glucocorticoid (GC) responsiveness of
      peripheral blood mononuclear cells (PBMC) from atopic asthmatics. A significant
      reduction (p < 0.001) in the GCR binding affinity (Kd) was observed in ragweed
      allergic asthmatics during ragweed pollen season compared with PBMC obtained
      before and after ragweed season. In vitro effects of allergen on PBMC GCR Kd were
      also examined by incubating PBMC from atopic asthmatics with allergen (ragweed
      and cat) versus Candida albicans. GCR binding affinity was significantly reduced
      after incubation with ragweed (p < 0.001) or cat allergen (p < 0.001) compared
      with baseline or C. albicans stimulation. This effect was limited to atopic
      asthmatics in that in vitro cat allergen incubation for 48 h failed to
      significantly alter GCR binding affinity in nonasthmatic, atopic individuals.
      These allergen-induced reductions in GCR binding affinity also rendered the PBMC
      less sensitive to the inhibitory effects of hydrocortisone and dexamethasone on
      allergen-induced proliferation (p < 0.01). To test the hypothesis that allergen
      induced alterations in GCR binding affinity were cytokine-induced, we examined
      the effects of interleukin-2 (IL-2)and IL-4 neutralization using anticytokine
      antibodies. Addition of both anti-lL-2 and anti-lL-4 antibodies resulted in a
      significant (p < 0.001) inhibition of allergen-induced alterations in GCR binding
      affinity. Furthermore incubation with cat allergen induced significantly higher
      concentrations of IL-2 (p = 0.03) and IL-4 (p = 0.02) by PBMC from atopic as
      compared with nonatopic subjects. Our current observations suggest that allergen
      exposure may contribute to poor asthma control by reducing GCR binding affinity
      in mononuclear cells. This appears to be mediated through IL-2 and IL-4. These
      findings may have important implications for novel approaches to the treatment of
      poorly controlled asthma.

PMID- 9001295
TI  - Aerodynamic properties of the major dog allergen Can f 1: distribution in homes,
      concentration, and particle size of allergen in the air.
AB  - Exposure and sensitization to dog allergen is a significant cause of asthma. In
      this study we investigated the distribution, aerodynamic characteristics, and
      particle-size distribution of the major dog allergen Can f 1. Dust samples were
      collected in 50 homes with a dog and 50 homes without dogs. Airborne Can f 1
      concentration was measured in 28 homes with dogs and 36 homes without a dog.
      Particle-size distribution was determined by using 10 separate Andersen sampler
      measurements in a dog-handling facility, and in 10 homes with dogs, and by
      repeated measurements in a home with one dog. High levels of Can f 1 (> 10
      microg/g) were found in dust in all but one home with a dog and in eight of 50
      homes without dogs. Airborne Can f 1 levels varied greatly between the homes with
      dogs (range: 0.3 to 99 ng/m3). Low levels of airborne Can f 1 (range: 0.4 to 1.1
      ng/m3) were detected in 11 of 36 homes without a dog. Can f 1 was predominantly
      associated with large particles collected on the first stage of the Andersen
      sampler (> 9 microm), which averaged 42 to 49% of the total allergen recovered in
      the dog-handling facility and in homes with dogs. Small particles (< 5 microm
      diameter) also carried Can f 1, and these particles comprised approximately 20%
      of the total airborne allergen load. There was an excellent concordance between
      the results obtained in different sampling areas, and between the total Can f 1
      recovered on the Andersen sampler and on the parallel filter. In conclusion,
      airborne Can f 1 was detectable in undisturbed conditions in all homes with dogs
      and in almost one third of the homes without dogs. In houses with dogs, a
      significant proportion (approximately 20%) of airborne Can f 1 was associated
      with small particles (< 5 microm diameter). Owing to their aerodynamic
      characteristics, these particles would be expected to remain airborne for a long
      period and, when inhaled, could penetrate into the lower airways and initiate
      asthma attacks.

PMID- 9001296
TI  - Sequential evaluation of pulmonary function and bronchial hyperresponsiveness in
      patients with nasal polyposis: a prospective study.
AB  - Nasal polyposis (NP) is commonly associated with nonspecific bronchial
      hyperresponsiveness (BHR) and/or asthma. The aim of this prospective study was to
      investigate the changes of pulmonary function and BHR in patients with nasal
      polyposis. Forty-four consecutive patients with NP were included in the study and
      were followed for 12 mo. Nonspecific BHR was assessed by a carbachol challenge
      test to determine the provocating dose (PD20) necessary to decrease FEV1 by 20%
      from baseline values; 17 of 22 patients who demonstrated BHR also exhibited
      asthma. Spirometric measurements and carbachol challenge were performed before
      initiating any treatment and 12 mo later. All patients were treated first with
      beclomethasone (600 microg/d). Intranasal ethmoidectomy was performed in 23
      patients who did not improve when treated with topical steroids alone
      (nonresponders); in contrast, 21 patients were successfully treated with
      beclomethasone alone (responders). PD20 significantly decreased in the group of
      nonresponders (p = 0.018), whereas it remained unchanged in responders (p =
      0.95). FEV1 (% pred) and FEF25-75 (% pred) significantly decreased in
      nonresponders (p < 0.001), whether BHR existed or not, whereas no significant
      change was observed in responders. Our results demonstrate that nonresponders who
      required nasal surgery exhibited an enhancement of BHR and a slight but
      significant decrease of FEV1 and FEF25-75 values. However, no change in pulmonary
      symptoms and/or asthma severity occurred. Clinical and functional follow-up of
      these patients should assess the long-term evolution of these parameters and
      their clinical relevance.

PMID- 9001298
TI  - Qualitative aspects of exertional breathlessness in chronic airflow limitation:
      pathophysiologic mechanisms.
AB  - We compared qualitative aspects of the sensory experience of exertional
      breathlessness in normal subjects and in patients with chronic airflow limitation
      (CAL) and sought a physiologic rationale for these. Twelve patients (66 +/- 2 yr
      of age, mean +/- SEM) with severe CAL (FEV1 = 37 +/- 5% predicted) and 12 age
      matched normal subjects (FEV1 = 103 +/- 5% predicted) were studied. Perceived
      inspiratory difficulty (BorgIN), inspiratory effort (esophageal pressure
      expressed as a fraction of maximal esophageal pressure at isovolume [Pes/PImax]),
      breathing pattern, and operational lung volumes (end-expiratory/inspiratory lung
      volumes [EELV/EILV]) were measured during symptom-limited incremental cycle
      exercise testing and compared at a standard VO2 of 50% predicted maximum in
      normal subjects and in patients with CAL. Qualitative descriptors of
      breathlessness were selected immediately after exercise. Breathlessness was
      qualitatively different between normal subjects and patients with CAL. Both
      normal subjects and patients with CAL chose descriptors of increased
      "work/effort" and "heaviness" of breathing; however, only patients with CAL
      consistently chose descriptors denoting "increased inspiratory difficulty" (75%),
      "unsatisfied inspiratory effort" (75%), and "shallow breathing" (50%). Stepwise
      regression analysis identified the ratio of Pes/PImax to VT/predicted VC as the
      strongest correlate of standardized BorgIN (n = 24, r = 0.86, p < 0.001). This
      latter measurement, which reflects the relationship between effort and
      ventilatory output, correlated strongly with dynamic EELV/TLC at isotime (r =
      0.78, p < 0.001). In conclusion, the qualitatively discrete respiratory
      sensations of exertional inspiratory difficulty peculiar to patients with CAL may
      have their origins in thoracic hyperinflation and the resultant disparity between
      inspiratory effort and ventilatory output.

PMID- 9001297
TI  - Inhaled salmeterol or oral theophylline in nocturnal asthma?
AB  - Nocturnal cough and wheeze are common in asthma and often treated with beta2
      agonists or theophyllines. As nocturnal asthma and these therapies may affect
      sleep and cognition, we compared 50 microg salmeterol inhaled every 12 h with
      individually dose-titrated sustained-release oral theophylline on sleep quality
      and cognitive performance in 15 patients with stable nocturnal asthma (overnight
      peak expiratory flow rate [PEFR] fall > or = 15%, > or = 1 asthmatic
      awakening/week) using a double-blind, double-dummy, crossover design with 14-d
      therapy limbs. Cognitive testing and polysomnography were performed on Nights 13
      and 14. Trough plasma theophylline concentration after Night 14 on theophylline
      was median 11.1 (interquartile range 8.3, 15.2) microg/ml. Overnight PEFR falls
      were similar [salmeterol 2.3 (0, 10.6), theophylline 3.5 (-0.3, 9.6)%, p = 0.4]
      but on salmeterol there were more nights without awakenings [median difference 1
      (0, 2), p < 0.01], fewer nocturnal arousals [difference -3 (-7, 2) h(-1), p <
      0.05] and improved quality of life (p = 0.05). Sleep architecture did not
      otherwise differ. Visual vigilance improved on salmetrol (p < 0.05), but
      otherwise daytime cognition was unaffected. There was no patient preference for
      either therapy. Hence in patients with nocturnal asthma, we demonstrate no major
      clinical advantage, but a small benefit in sleep quality, quality of life, and
      daytime cognitive function with salmeterol.

PMID- 9001299
TI  - Ozone responsiveness in smokers and nonsmokers.
AB  - Short-term exposure to ozone causes decrements in lung function, but predictors
      of responsiveness remain largely unknown. Ninety healthy volunteers (56 never
      smokers, age [mean +/- SD] 25 +/- 4 yr; 34 current smokers, 13 +/- 9 pack-yr, age
      28 +/- 1 yr) were exposed to 0.22 ppm ozone for 4 h, with exercise, in an
      environmental chamber. We measured spirometry and specific airway conductance
      before, during, and immediately after exposure, and assessed symptoms by
      questionnaire. Smokers experienced a smaller increase in respiratory symptoms
      following exposure to ozone than did nonsmokers. Decrements in FEV1 were
      significantly less than for smokers than for nonsmokers (p = 0.0013). Ozone
      responsiveness (> 15% fall in FEV1) occurred in 16 of 56 never-smokers (28.6%)
      and 4 of 34 smokers (11.8%). Multiple logistic regression analysis found pack-yr
      of smoking to be associated with decreased ozone responsiveness (odds ratio [OR]
      0.87, p = 0.017). Age, gender, and methacholine responsiveness were not
      predictive of responder status. Fourteen smokers and 25 nonsmokers were
      subsequently exposed once to air and twice to ozone; smokers as well as
      nonsmokers were consistent in their subsequent responsiveness (or lack of
      responsiveness) to ozone. Healthy smokers have smaller decrements in lung
      function and fewer symptoms in response to ozone exposure than do nonsmokers.

PMID- 9001300
TI  - Lung function and long term exposure to air pollutants in Switzerland. Study on
      Air Pollution and Lung Diseases in Adults (SAPALDIA) Team.
AB  - The effect of long-term exposure to air pollutants was studied in a cross
      sectional population-based sample of adults (aged 18 to 60 yr; n = 9,651)
      residing in eight different areas in Switzerland. Standardized medical
      examination included questionnaire data, lung function tests, skin-prick testing,
      and end-expiratory CO concentration. The impact of annual means of air pollutants
      on FVC and FEV1 was tested (controlling for age and age squared, sex, height,
      weight, educational level, nationality, and workplace exposure). Analyses were
      done separately for healthy never-smokers, ex-smokers (controlling for pack-yr),
      for current smokers (controlling for cigarettes per day and pack-yr smoked), and
      for the whole population. Significant and consistent effects on FVC and FEV1 were
      found for NO2, SO2, and particulate matter < 10 microm (PM10) in all subgroups
      and in the total population, with PM10 showing the most consistent effect of a
      3.4% change in FVC per 10 microg/m3. Results for ozone were less consistent.
      Atopy did not influence this relationship. The limited number of study areas and
      high intercorrelation between the pollutants make it difficult to assess the
      effect of one single pollutant. Our conclusion is that air pollution from fossil
      fuel combustion, which is the main source of air pollution with SO2, NO2, and
      PM10 in Switzerland, is associated with decrements in lung function parameters in
      this study.

PMID- 9001302
TI  - Relationship between loss in parenchymal elastic recoil pressure and maximal
      airway narrowing in subjects with alpha1-antitrypsin deficiency.
AB  - Airway hyperresponsiveness is characterized by an increase in sensitivity and
      excessive airway narrowing to inhaled bronchoconstrictor stimuli. There is
      experimental evidence that maximal airway narrowing is related to lung elasticity
      in normal and asthmatic subjects. We hypothesized that reduced lung elasticity by
      parenchymal destruction increases the level of maximal airway narrowing in
      subjects with alpha1-antitrypsin deficiency. To that end, we measured complete
      dose-response curves to methacholine, quasistatic pressure-volume (P-V) curves,
      diffusion capacity for carbon monoxide per unit lung volume (DLCO/VA), and mean
      lung density by spirometrically controlled computed tomography (CT) scan in eight
      non- or ex-smoking subjects with alpha1-antitrypsin deficiency. Methacholine dose
      response curves were expressed as the provocative concentration causing 20% fall
      in FEV1 (PC20). A maximal response plateau was considered if > or = 3 highest
      doses fell within a 5% response range, the maximal response (MFEV1) being the
      average value on the plateau. The P-V curves were characterized by an index of
      compliance (exponent K), and elastic recoil pressures at 90, and 100% of TLC
      (PL90 and PLmax). In all subjects a complete dose-response curve to methacholine
      could be recorded. MFEV1 was significantly correlated with logPC20 (r = -0.94, p
      < 0.001), but not with baseline FEV1 (r = -0.53, p > 0.15). There was a
      significant relationship between MFEV1 and PL90 (r = -0.79, p < 0.02), PLmax (r =
      -0.87, p < 0.005), and K (r = 0.79, p < 0.02). Furthermore MFEV1 was
      significantly correlated with DLCO/VA (r = -0.76, p < 0.03) and with lung density
      (r = 0.78, p < 0.04). We conclude that in subjects with alpha1-antitrypsin
      deficiency the level of maximal airway narrowing increases with loss in lung
      elasticity, with reduction in diffusing capacity, and with lowered mean lung
      density. This suggests that loss in elastic recoil pressure secondary to
      parenchymal destruction contributes to excessive airway narrowing in humans in
      vivo.

PMID- 9001301
TI  - Chronic, episodic, reversible airway obstruction after viral bronchiolitis in
      rats.
AB  - Viral bronchiolitis in human infants has been associated with persistent airway
      abnormalities, but not proven as a cause. Previously we observed some adult rats
      had airway obstruction and hyperresponsiveness following bronchiolitis at an
      early age. The purpose of this study was to determine, via serial measurements of
      lung mechanics, whether the postbronchiolitis airway obstruction was episodic or
      continuous, and to determine the magnitude and duration of glucocorticoid
      effects. Rats were either virus- (n = 14) or sham-inoculated (n = 8) at 3 wks of
      age. Lung mechanics were measured 6 times in each rat at postinoculation Weeks 11
      18. Half the rats in each group were treated with dexamethasone for 3 d at Week
      15. The virus group had higher lung resistance (p = 0.03) and lower dynamic
      compliance (p = 0.005) than control rats, with airway obstruction occurring in an
      episodic pattern. Dexamethasone treatment had a transient effect in
      postbronchiolitis rats; lung resistance normalized in Week 15 (p = 0.006), then
      returned to pretreatment levels by Weeks 16-18. We conclude that viral
      bronchiolitis in rats can result in a chronic syndrome of intermittent,
      reversible airway obstruction which has multiple parallels with human asthma over
      a prolonged time period.

PMID- 9001303
TI  - Heavy habitual marijuana smoking does not cause an accelerated decline in FEV1
      with age.
AB  - To assess the possible role of daily smoking of marijuana in the development of
      chronic obstructive pulmonary disease (COPD), we evaluated the effect of habitual
      use of marijuana with or without tobacco on the age-related change in lung
      function (measured as FEV1) in comparison with the effect of nonsmoking and
      regular tobacco smoking. A convenience sample of 394 healthy young Caucasian
      adults (68% men; age: 33 +/- 6 yr; mean +/- SD) including, at study entry, 131
      heavy, habitual smokers of marijuana alone, 112 smokers of marijuana plus
      tobacco, 65 regular smokers of tobacco alone, and 86 nonsmokers of either
      substance were recruited from the greater Los Angeles community. FEV1 was
      measured in all 394 participants at study entry and in 255 subjects (65 %) on up
      to six additional occasions at intervals of > or = 1 yr (1.7 +/- 1.1 yr) over a
      period of 8 yr. Random-effects models were used to estimate mean rates of decline
      in FEV1 and to compare these rates between smoking groups. Although men showed a
      significant effect of tobacco on FEV1 decline (p < 0.05), in neither men nor
      women was marijuana smoking associated with greater declines in FEV1 than was
      nonsmoking, nor was an additive effect of marijuana and tobacco noted, or a
      significant relationship found between the number of marijuana cigarettes smoked
      per day and the rate of decline in FEV1. We conclude that regular tobacco, but
      not marijuana, smoking is associated with greater annual rates of decline in lung
      function than is nonsmoking. These findings do not support an association between
      regular marijuana smoking and chronic COPD but do not exclude the possibility of
      other adverse respiratory effects.

PMID- 9001304
TI  - Pulmonary function until two years of life in infants with bronchopulmonary
      dysplasia.
AB  - To evaluate the physiologic course of pulmonary function in infants with
      bronchopulmonary dysplasia (BPD) weighing less than 1,250 g at birth, 24 infants
      with BPD underwent serial pulmonary function evaluations from birth until 2 yr of
      age. All infants were intubated at birth and the mean duration of mechanical
      ventilation was 38 +/- 4 d. Passive respiratory system compliance (Crs) and
      resistance (Rrs) were measured between 10 and 20 d of life during mechanical
      ventilation. Thereafter pulmonary mechanics and functional residual capacity
      (FRC) were evaluated at 3, 6, 9, 12, and 24 mo of postnatal age. Forced
      expiratory flow (Vmax,FRC) was measured at 2 yr of age. A severe alteration on
      Crs (50% of predicted) was found during the acute phase of BPD, associated with
      abnormal values of Rrs. A progressive improvement (ANOVA, p < 0.0001) occurred in
      the first year of life and, at 24 mo of age, Crs and Rrs reached the range of
      normalcy. FRC value was 86 +/- 7.5% of predicted at 3 mo and gradually increased
      to a mean value of 115 +/- 5% of predicted at 2 yr of age. In spite of the good
      resistance time course over the 2-yr evaluation, less favorable data of Vmax,FRC
      were found with individual values reduced more than 40% of predicted values in
      70% of the children. In conclusion, although pulmonary mechanics of BPD survivors
      improves during the first years of life, reaching the range of normal values, at
      2 yr of age they still present a substantial airway function impairment as
      revealed by the low forced expiratory flows.

PMID- 9001305
TI  - Lower respiratory illness, recurrent wheezing, and day care attendance.
AB  - We prospectively assessed the relations between various characteristics of day
      care and lower respiratory illness (LRI) in a cohort of 1,268 Minnesotan
      children, born between October 1989 and January 1991 and followed to 2 yr of age.
      Information on LRI was abstracted from medical records and data on day care use,
      respiratory symptoms, and physician diagnosis of asthma were obtained from
      questionnaires. We identified a subgroup of 60 children with recurrent wheezing
      illnesses. The LRI rate ratio for day care attendance was 2.0 (95% confidence
      interval = 1.7, 2.2). Rate ratios were similar regardless of the day care
      setting, number of other children present, or the number of hours spent in day
      care. A parental history of asthma further increased the rate ratio for day care
      attendance. Day care attendance was associated with a threefold risk of having
      recurrent wheezing illnesses. We conclude that day care attendance is an
      important risk factor for LRI in young children, and for recurrent wheezing
      illnesses.

PMID- 9001306
TI  - Nosocomial pneumonia and tracheitis in a pediatric intensive care unit: a
      prospective study.
AB  - We conducted a prospective study in the multidisciplinary pediatric intensive
      care unit (pediatric ICU) of a tertiary-care university hospital in order to
      determine the incidence, risk markers, risk factors, and complications related to
      bacterial nosocomial pneumonia (BNP) and tracheitis (BNT) in children. A cohort
      of 1,114 consecutive admissions to the pediatric ICU was enrolled over a 56-wk
      period; 154 cases were excluded mostly (75%) because they already had a
      respiratory infection at entry. The final sample included 960 admissions (831
      patients). Diagnosis of BNP or BNT was based on Centers for Disease Control of
      Atlanta criteria using a consensus method involving three experts, who also
      attributed complications to BNP and BNT. A total of 29 BNP and BNT (3.0%; 95% CI:
      1.1 to 4.1%) were diagnosed (BNP: 1.2%, 95% CI: 0.7 to 1.9%; BNT: 1.8%, 95% CI:
      0.8 to 2.6%). Three factors were retained by multivariate analysis as independent
      risk factors or markers for BNP (immunodeficiency, immunosuppression, and
      neuromuscular blockade), and two for BNT (head trauma and respiratory failure).
      Gram-negative bacteria and Staphylococcus aureus were the microorganisms most
      frequently found in the tracheal aspirates. Prescription of antibiotics was
      commonly attributable to BNP (75%) and BNT (59%). Death, as well as multiple
      organ system failure, resulted from BNP in 8% of cases, but never from BNT. In
      BNT, the reintubation rate was 24%. Nosocomial bacterial respiratory infections
      are rare in critically ill children. However, BNP causes significant
      complications, and more attention should be focused on BNT in the critically ill
      child.

PMID- 9001307
TI  - Effect of inhaled indomethacin on exercise-induced bronchoconstriction in
      children with asthma.
AB  - We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory
      drug (NSAID), on exercise-induced bronchoconstriction (EIB) in children with
      asthma. Nine asthmatic children (7 boys, 2 girls, with a mean +/- SEM age of 11.0
      +/- 0.8 yr) with a history of EIB participated in this study. These subjects were
      pretreated with inhaled indomethacin (3 mg/m2 body surface area [BSA]) or placebo
      (0.9% saline) according to a double-blind, randomized, crossover design, and
      underwent an exercise challenge test 15 min after the pretreatment. Inhaled
      indomethacin significantly attenuated EIB. The mean maximal percent decrease in
      FEV1 following exercise was 36.1 +/- 5.7% after placebo and 18.0 +/- 4.6% after
      indomethacin pretreatment (p = 0.0310). Indomethacin also significantly reduced
      the mean maximal decrease in arterial oxygen saturation after exercise (p =
      0.0378). The inhibition of local prostaglandin synthesis and/or ion transport in
      the airways may be a mechanism involved in the protective potency of inhaled
      indomethacin.

PMID- 9001308
TI  - Long-term pulmonary sequelae in children with congenital diaphragmatic hernia.
AB  - Neonates with congenital diaphragmatic hernia (CDH) often suffer from respiratory
      insufficiency due to lung hypoplasia and pulmonary hypertension. Artificial
      ventilation is frequently required, and this leads to a high incidence of
      bronchopulmonary dysplasia. Long-term follow-up studies have shown persisting
      airway obstruction. To evaluate the long-term pulmonary sequelae in CDH, we
      studied 40 CDH patients of age 7 to 18 yr (median 11.7 yr) and 65 age-matched
      controls without CDH and lung hypoplasia who underwent similar neonatal
      treatment. Mild airway obstruction was found in both groups with more peripheral
      airway obstruction in CDH patients than in control subjects. Both groups had
      normal TLC and single-breath carbon monoxide diffusion capacity (DLCO). CDH
      patients had increased residual volume (RV) and RV/TLC compared with controls.
      Increased airway responsiveness to methacholine (MCH) was common but
      bronchoconstriction to inhaled metabisulfite (MBS) was rare both in CDH and
      control subjects. We conclude that this group of CDH patients has minor residual
      lung function impairment. Mild airway obstruction and increased airway
      responsiveness to inhaled MCH but not to MBS suggest that structural changes in
      distal airways are involved and not autonomic nerve dysfunction. Both artificial
      ventilation in the neonatal period and residual lung hypoplasia seem important
      determinants of persistent lung function abnormalities in CDH patients.

PMID- 9001309
TI  - Broxaterol increases force output of fatigued canine diaphragm more than
      salbutamol.
AB  - We previously demonstrated that broxaterol enhanced recovery of fatigued canine
      diaphragm. The aim of this study was to compare the inotropic effects of
      salbutamol and broxaterol on fatigued canine diaphragm. Low-frequency fatigue was
      induced in 14 mongrel dogs by electrophrenic stimulation, which was continued
      until transdiaphragmatic pressure (Pdi) at 20 Hz was reduced by 50% or for 1 h.
      After stabilization of fatigue, the animals received a bolus (18.5 microg/kg) of
      either broxaterol or salbutamol, followed by a continuous infusion (0.43
      microg/kg/min). A second bolus of 74.0 microg/kg, followed by a continuous
      infusion of 1.72 microg/kg/min, was given after 90 min. Both drugs significantly
      increased twitch Pdi. Twitch Pdi measured 90 min after the first and second doses
      of broxaterol increased by 28 +/- 23% and 42 +/- 34%, respectively, whereas the
      salbutamol-induced increase was clearly smaller (9 +/- 10% and 17 +/- 15%,
      respectively). Broxaterol increased Pdi at 20 Hz by 25 +/- 28% with the first
      dose and by 29 +/- 21% with the second dose. In contrast, salbutamol did not
      alter Pdi at 20 Hz. Neither drug affected Pdi at 100 Hz. We conclude that
      broxaterol promoted recovery of low-frequency fatigue of the canine diaphragm in
      vivo in a dose-dependent manner, whereas salbutamol only minimally improved force
      production by the fatigued diaphragm.

PMID- 9001311
TI  - Pulmonary artery pressure response to hypoxia in sleep apnea.
AB  - The pulmonary artery pressure (Ppa) responses to short runs of acute hypoxia at
      two different levels of end-tidal CO2 were measured in nine normal subjects and
      in 20 patients with moderate to severe obstructive sleep apnea (OSA). In normal
      subjects the mean increase in Ppa in response to eucapnic hypoxia was 8 +/- 2 mm
      Hg (SEM) and was not different from the response to hypercapnic hypoxia (9 +/- 2
      mm Hg, p > 0.2). In patients with OSA, the mean increase of Ppa was 8 +/- 1 mm Hg
      to eucapnic hypoxia, and the response to hypercapnic hypoxia was higher at 10 +/-
      1 mm Hg (p = 0.01). Pulmonary pressor response to hypoxia was augmented (> 10 mm
      Hg) by hypercapnia in four of 20 patients with OSA but in none of the normal
      subjects. Normoxic hypercapnia alone was a weak stimulus, increasing Ppa by > 5
      mm Hg in only two of nine patients with OSA studied. In conclusion, Ppa increases
      in both normal subjects and patients with OSA exposed to a ramp of acute
      isocapnic hypoxia. There were clear interindividual differences in pulmonary
      artery response. Hypercapnia did not produce clinical significant changes in Ppa
      in either group.

PMID- 9001310
TI  - Racial differences in sleep-disordered breathing in African-Americans and
      Caucasians.
AB  - In this case-control family study of sleep-disordered breathing (SDB), we
      describe the distributions of SDB and SDB risk factors in African-Americans and
      Caucasians. A total of 225 African-Americans and 622 Caucasians, ages 2 to 86 yr,
      recruited as members of families with an individual with known sleep apnea (85
      index families) or as members of neighborhood control families (63 families) were
      studied with an overnight home sleep-study, questionnaires, and physical
      measurements. A subsample underwent cephalometry. Outcome measures were the
      respiratory disturbance index (RDI) and a binary variable indicating the presence
      of increased apneic activity (IAA). In both races, a strong relationship was
      demonstrated between the (log transformed) RDI and age and age2. African
      Americans with SDB were younger than Caucasians with SDB (37.2 +/- 19.5 versus
      45.6 +/- 18.7 yr, p < 0.01). In subjects < or = 25 yr, RDI level and IAA
      prevalence were higher in African-Americans (odds ratio, adjusted for obesity,
      sex, proband sampling, and familial clustering, 1.88, 1.03 to 3.52, 95% CI). In
      this age group, racial differences also were observed in the relationship between
      RDI and age (p < 0.001 for the RDI-age interaction). This suggests that young
      African-Americans may be at increased risk for sleep apnea.

PMID- 9001312
TI  - Effects of sleep posture on upper airway stability in patients with obstructive
      sleep apnea.
AB  - Changes in sleep posture have been shown to improve obstructive sleep apnea
      (OSA). To investigate the mechanisms by which this occurs we assessed upper
      airway stability in eight patients with severe OSA in three postures (supine,
      elevated to 30 degrees, and lateral). We used a specially adapted nasal
      continuous positive airway pressure (nCPAP) mask to measure upper airway closing
      pressure (UACP) and upper airway opening pressure (UAOP) during non-REM sleep.
      Statistical comparisons were made between postures using ANOVA for repeated
      measures. Elevation resulted in a less collapsible airway compared with both the
      supine and lateral positions (mean UACP: 30 degrees elevation -4.0 +/- 3.2
      compared with supine 0.3 +/- 2.4 cm H2O, p < 0.05 and; lateral -1.1 +/- 2.2 cm
      H2O, p < 0.05). Supine UACP and lateral UACP were not significantly different.
      Elevation or lateral positioning produced a 50% reduction in mean UAOP (supine
      10.4 +/- 3.5 cm H2O compared with 30 degrees elevation 5.3 +/- 2.1, p < 0.05; and
      lateral 5.5 +/- 2.1 cm H2O, p < 0.05). We conclude that in severely affected OSA
      patients upper body elevation, and to a lesser extent lateral positioning,
      significantly improve upper airway stability during sleep, and may allow
      therapeutic levels of nCPAP to be substantially reduced.

PMID- 9001313
TI  - Effects of menopause and nasal occlusion on breathing during sleep.
AB  - Prevalence of sleep-disordered breathing (SDB) is reported to increase in
      menopausal women. We examined response to a nocturnal respiratory challenge
      (nasal occlusion) during overnight polysomnography in 31 women (45 to 55 yr).
      Thirteen were premenopausal, four perimenopausal, and 14 postmenopausal by
      history and hormonal assay. Nasal occlusion increased the apnea hypopnea index
      (AHI) (occlusion mean = 6.6 +/- 8.0 versus baseline mean = 1.6 +/- 2.6, p < 0.01)
      and arousal index (occlusion mean = 35.1 +/- 20.1 versus baseline mean = 20.7 +/-
      11.6, p < 0.001), but did not change the oxygen saturation nadir in those with
      respiratory events (occlusion mean = 91.8 +/- 4.2 versus baseline mean = 92.0 +/-
      11.6). Menopausal groups did not differ on AHI, arousal index, or oxygen
      saturation nadir in either condition. Key variables were compared between
      occlusion responders (n = 11) and nonresponders (n = 20). Responders and
      nonresponders were not distinguished by age, menopausal status, nor several
      cephalometric or anthropometric variables. Body mass index (31.1 +/- 8.5 versus
      24.3 +/- 3.4, p < 0.003), neck circumference (34.0 +/- 2.5 versus 32.5 +/- 1.7
      cm, p < 0.05), and mandibular-hyoid distance (18.5 +/- 3.8 versus 14.5 +/- 5.7
      mm, p < 0.05) were greater in responders. These findings suggest hormonal factors
      may be less important than weight and facial morphology in midlife development of
      SDB in women.

PMID- 9001314
TI  - Evaluation of nasal prongs for estimating nasal flow.
AB  - Nasal prongs (NP) connected to a pressure transducer have been suggested as a
      useful alternative for measuring nasal flow in sleep apnea/hypopnea patients.
      However, flow measured with NP is expected to be nonlinear. The aim of the
      present study was to analyze and correct the nonlinearity of nasal flow
      measurements with NP (VNP). Nasal flow was simultaneously measured with a
      pneumotachograph (PNT; V) and (NP; VNP) in six healthy subjects during 60 s of
      breathing at different tidal volumes. Nonlinearity of VNP was assessed by fitting
      separately, for inspiration and expiration, a Rorher-model equation (VNP x K1 x V
      + K2 x V2). In addition, we fitted the data to a simpler nonlinear quadratic
      model (P = K x V2). The main findings were: (1) an excellent fit of the Rorher
      equation to measured data in all cases; (2) although differences in the Rorher
      equation coefficients between inspiration and expiration were observed, they were
      not statistically significant; (3) a substantial intersubject variability was
      found; and finally, (4) the square root of VNP acceptably fitted the nasal flow
      data measured by PNT (V) in most cases. We conclude that in order to
      quantitatively assess nasal flow with NP, data should be corrected for their
      nonlinear pressure-flow relationships and, that the square root of the flow
      signal measured with NP is the simplest method of correcting for the observed
      nonlinearity.

PMID- 9001315
TI  - Time course of hypoxic pulmonary vasoconstriction: a rabbit model of regional
      hypoxia.
AB  - There is disagreement in the literature about the time required for hypoxic
      constriction of pulmonary vessels to reach its full intensity. Some studies
      suggest that only minutes are required, others that several hours are needed. We
      examined the time course over 6 h of changes in pulmonary shunt (as a fraction of
      cardiac output) following induction of unilateral hypoxia by collapse or liquid
      filling of the left lung in 47 anesthetized rabbits. The time course was examined
      at four degrees of lung inflation: during collapse and at airway pressures of 0.3
      kPa, 0.6 kPa, and 0.9 kPa. The respective volumes (mean +/- SD) of the liquid
      filled lung were estimated to be 6.4 +/- 1.0, 12.8 +/- 2.5, and 15.8 +/- 1.6
      ml/kg body weight (BW). During sustained hypoxia (the period from 150 to 360 min
      after inducing hypoxia), shunt declined at a slow linear rate of 2.37 x 10(
      4)/min, which was independent of lung inflation (p = 0.65 analysis of variance
      [ANOVA]) and significantly different from zero (p < 0.001). The stability of
      cardiac output in this animal model, as measured sequentially by thermodilution,
      was confirmed in a further 20 animals. The experiments provide evidence for a
      slow intensification of blood-flow diversion at a rate that does not depend upon
      the degree of lung inflation. Whether this change is a feature of hypoxic
      constriction itself, or some modulation of it, remains unclear.

PMID- 9001316
TI  - Myocardial anaerobic metabolism occurs at a critical coronary venous PO2 in pigs.
AB  - We tested the hypothesis that the onset of myocardial anaerobic metabolism is
      fundamentally different from the whole body and other organs, where the onset of
      anaerobic metabolism occurs at a critical oxygen extraction ratio--not at a
      critical venous PO2. We measured oxygen saturation and PO2 of arterial and
      coronary venous blood at the onset of global myocardial anaerobic metabolism
      during progressive hypoxic hypoxia (n = 7) compared with carbon monoxide hypoxia
      (n = 7), which left-shifted the oxygen-hemoglobin dissociation curve. The onset
      of global myocardial anaerobic metabolism was defined by decreased myocardial
      lactate consumption and left ventricular contractility. Coronary venous PO2 was
      no different during hypoxic hypoxia and carbon monoxide hypoxia at equivalent
      arterial oxygen saturations, particularly at the onset of myocardial anaerobic
      metabolism (PO2 17.0 +/- 1.7 torr versus 15.9 +/- 2.2 torr, p = NS). However, the
      myocardial oxygen extraction ratio was significantly greater during hypoxic
      hypoxia than during carbon monoxide hypoxia at the onset of myocardial anaerobic
      metabolism (0.88 +/- 0.02 versus 0.65 +/- 0.04, p < 0.01). Thus, in contrast to
      the whole body where the onset of anaerobic metabolism occurs at a critical
      oxygen extraction ratio, the onset of myocardial anaerobic metabolism occurs at a
      critical coronary venous PO2.

PMID- 9001317
TI  - Effect of hypoxia and carbon monoxide on muscle oxygenation during exercise.
AB  - We used near-infrared spectroscopy (NIRS) to test the hypothesis that reducing
      oxygen availability during exercise would affect the rate of muscle oxyhemoglobin
      (O2Hb) desaturation when performing work above the lactic acidosis threshold
      (LAT), but not below it. Seven healthy men each performed two constant work
      intensities (60%LAT and the LAT plus 40% of the difference between the LAT and
      VO2max [40%delta]) four times under the following conditions: (1) 10 min air; (2)
      5 min 15%O2 + 5 min air; (3) 5 min air + 5 min 15%O2; (4) 5 min after carbon
      monoxide (CO) loading to increase the carboxyhemoglobin (COHb) saturation to 15%.
      During each test, cardiorespiratory parameters and muscle oxygenation measured
      with NIRS were continuously monitored. Forearm venous blood lactate was measured
      every 2 to 3 min. Hypoxia and CO accelerated muscle deoxygenation only for
      exercise above the LAT; for exercise below the LAT, neither progressive
      deoxygenation nor lactate accumulation occurred after initital, rapid muscle
      deoxygenation. The rate of decrease in muscle oxygenation between 3 to 5 min of
      exercise correlated with the increase in VO2 (r = 0.61, p < 0.01) and blood
      lactate (r = 0.70, p < 0.01) over the same period. These results support the
      hypothesis that progressive muscle deoxygenation occurs above the LAT and that
      the rate of deoxygenation is sensitive to oxygen delivery.

PMID- 9001318
TI  - Adjustment of DLCO for hemoglobin concentration.
AB  - The equation proposed by Cotes and coworkers is currently considered as the most
      acceptable to correct carbon monoxide diffusing capacity (DLCO) for hemoglobin
      concentration [Hb] by both the American Thoracic Society (ATS) and the European
      Respiratory Society (ERS) guidelines for standardization of DLCO. In a previous
      study on 24 anemic patients undergoing bone marrow transplantation (1), we found
      that DLCO is underestimated using the equation of Cotes and coworkers. To further
      explore this finding, 28 anemic patients ([Hb] = 8.2 +/- 1.0 (SD) g/dl) with
      chronic renal failure were prospectively studied during the recovery period of
      anemia (5.4 +/- 3.5 mo). In all 28 subjects, the slope deltaDLCO/delta[Hb]
      computed as ratio of overall change in DLCO to overall change in [Hb] throughout
      the study period was 1.40 +/- 0.72 ml CO/min/mm Hg/g/dl. The individual
      relationship between measured DLCO and [Hb] closely fitted a simple linear
      regression. The resulting equations for adjustment of DLCO (DLCOadj) to a
      standard [Hb] of 14.6 g/dl for men and 13.4 g/dl for women are: [equations: see
      text]. The present adjustment function for DLCO is linear and independent of the
      observed DLCO values, whereas the formulas previously proposed are curvilinear,
      DLCO correction varying with the measured DLCO values. For a measured DLCO of 15
      ml CO/min/mm Hg and [Hb] ranging from 7 to 12 g/dl, the present DLCO adjustment
      is higher (by 2.7 ml CO/min/mm Hg, on average) than that proposed by Cotes and
      coworkers. This difference appears to be relevant for a precise interpretation of
      DLCO in patients with normocytic anemia in different clinical conditions.

PMID- 9001319
TI  - Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis.
AB  - We conducted a multicenter case-control study of clinically and histologically
      diagnosed idiopathic pulmonary fibrosis (IPF), a chronic diffuse interstitial
      lung disease of unknown cause. The study included 248 cases, and 491 control
      subjects identified through random-digit dialing, matched to cases in sex, age,
      and geographic region. Telephone interviews were conducted with both cases and
      controls to collect information on potential risk factors for IPF, including
      smoking and household, occupational, and environmental exposures. Pulmonary
      function tests, X-rays, computed tomographic (CT) scans of the chest, and lung
      biopsy reports were submitted by referring centers to support the diagnoses. An a
      priori hypothesis that smoking is associated with IPF was examined with
      conditional logistic regression analyses. More cases (72%) than control subjects
      (63%) had a history of ever smoking. The odds ratio (OR) for ever smoking was 1.6
      (95% CI: 1.1 to 2.4). Risk was significantly elevated for former smokers (OR =
      1.9; 95% CI: 1.3 to 2.9) and for smokers with 21 to 40 pack-yr (OR = 2.3; 95% CI:
      1.3 to 3.8). A history of smoking is associated with an increased risk for the
      development of IPF. Although there was no clear exposure-response pattern with
      cumulative consumption of cigarettes, there was a trend for time since cessation
      of smoking, with the highest risk for those who had most recently quit.

PMID- 9001320
TI  - Lung alkaline phosphatase as a marker of fibrosis in chronic interstitial
      disorders.
AB  - Alkaline phosphatase (ALP) in lung lavage fluids is a marker of tissue damage and
      type II cell proliferation. Type II pneumocytes are extensively involved in
      fibrosis. The aim of our study was to verify whether local ALP activity can be
      held as a marker of fibrosis in chronic interstitial lung disorders. ALP was
      determined in the bronchoalveolar lavage of 140 subjects: 25 control subjects,
      and 33 patients with silicosis, 38 with idiopathic pulmonary fibrosis (IPF), and
      18 with Stage I, 16 with Stage II, and 10 with Stage III/IV sarcoidosis. We
      observed a significant augmentation of ALP activity in patients with IPF, as well
      as in those with Stages II and III/IV sarcoidosis. Albumin was higher in those
      with Stages I and II sarcoidosis, but it was normal in the other groups.
      Therefore, a significant increase in ALP:albumin ratio characterized IPF (median,
      10.3; range, 2.4 to 83.2) and Stage III/IV sarcoidosis, (8.9, 4.4 to 103.1) as
      compared with Stage I (2, 1.1 to 18) and Stage II (4.7, 0.7 to 26.6) sarcoidosis,
      silicosis (6.5, 0.5 to 42.7), and the nonsmoker (6.1, 2.9 to 12.9) and smoker
      (6.4, 2 to 15.2) control groups. We conclude that an increase of the ALP: albumin
      ratio in bronchoalveolar lavage fluids from patients with chronic interstitial
      disorders may reflect a fibrosing progression.

PMID- 9001321
TI  - The kinetics of grain dust-induced inflammation of the lower respiratory tract.
AB  - To characterize the kinetics of grain dust-induced airflow obstruction and
      inflammation in the lower respiratory tract, we performed serial spirometry and
      bronchoalveolar lavage (BAL) in human subjects and whole-lung lavage in mice
      following a single inhalation exposure to comparable dosages of corn dust extract
      (CDE). Following inhalation of CDE, our human study subjects developed
      significant airflow obstruction 10 min postexposure which persisted for 48 h.
      Human subjects and mice had similar acute and persistent changes in lavage
      cellularity after exposure to CDE. A profound increase in the concentration of
      lavage neutrophils was present in the initial postexposure lavage in both human
      subjects and mice. This increase persisted for 96 h in human subjects and 48 h in
      mice. Small but significant increases in lavage macrophage concentration were
      present 48 h postexposure in human subjects and at 96 h postexposure in mice.
      Inhalation of CDE resulted in a significant increase in the concentration of
      proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin
      6 (IL-6) in the lavage fluid of both human subjects and mice. Similarly,
      significant increases in lavage concentrations of IL-8 in humans and macrophage
      inflammatory protein-2 (MIP-2) in mice occurred after inhalation of CDE. The
      lavage concentration of all measured proinflammatory cytokines returned to
      baseline levels by 168 h in humans and 96 h in mice. These findings suggest that
      a single inhalation challenge of CDE results in airflow obstruction and lower
      respiratory tract inflammation that may last for several days. These physiologic
      and inflammatory responses appear to be self-limited with no evidence of
      persistent injury 1 wk after the inhalation challenge. Moreover, the inflammatory
      response in the lower respiratory tract after inhalation of grain dust is similar
      in human subjects and mice, suggesting that the mouse may be an appropriate model
      for further investigation of grain dust-induced inflammation.

PMID- 9001322
TI  - Marked flow-dependence of exhaled nitric oxide using a new technique to exclude
      nasal nitric oxide.
AB  - Exhaled nitric oxide (NO) may aid in monitoring pulmonary disease. The single
      breath NO profile (subjects with nose clip) was described as a NO peak followed
      by a plateau (NO(PLAT)). Published exhaled NO values vary greatly, possibly due
      to contamination with nasal NO and differing respiratory maneuvers. We developed
      a technique to measure pulmonary NO, without nasal NO, by having the subject
      maintain a positive expiratory pressure (ensuring vellum closure), and we
      examined the variation in NO(PLAT) over a range of expiratory flows (4.2 to 1,550
      ml/s). NO(PLAT) values rose almost 35-fold (3.2 +/- 1.4 ppb to 110.5 +/- 54.8
      ppb) with decreasing flow, described by NO(PLAT) = 208.6795 x (flow rate)(
      0.5995). However, NO excretion showed an almost 11-fold rise as flow increased.
      In summary, we present a simple technique for measuring exhaled NO without
      contamination by nasal NO. There is a marked flow dependence of exhaled NO
      concentration and excretion. Exhaled pulmonary NO is best measured at very low
      flow rates to amplify the signal and must be related to the expiratory flow
      employed.

PMID- 9001323
TI  - Human lung mononuclear cells induce nitric oxide synthase in murine airway
      epithelial cells in vitro: role of TNFalpha and IL-1beta.
AB  - Nitric oxide (NO) is a gas released by the airway epithelium, but the mechanism
      regulating NO release is unclear. We hypothesized that lung mononuclear cell
      release of tumor necrosis factor alpha (TNF) and interleukin-1beta (IL-1) would
      induce epithelial cells to release NO. Lung mononuclear cells were obtained from
      seven normal volunteers by bronchoalveolar lavage and cultured with Escherichia
      coli lipopolysaccharide for 24 h. The mononuclear cell culture-conditioned media
      (M-CM) were then applied to cultures of the murine lung epithelial cell line, LA
      4. Nitrite and nitrite + nitrate concentrations were 0.9 +/- 0.1 and 11.8 +/- 2.4
      microM in the M-CM. Culturing LA-4 cells line with the M-CM (1:10 dilution)
      resulted in a marked and time-dependent increase in nitrite or nitrite + nitrate
      compared with LA-4 cells cultured in media alone (2.4 +/- 0.5 versus 0.9 +/- 0.1
      microm and 16.6 +/- 0.6 versus 11.8 +/- 2.4 microM after 24 h). Antibodies to TNF
      and/or IL-1 significantly reduced the nitrite or nitrite + nitrate concentrations
      and the concentrations of TNF and IL-1 in the M-CM correlated with nitrite
      concentrations in the LA-4 culture supernatant fluids (r2 = 0.848 and 0.956).
      Inducible nitric oxide synthase (iNOS) protein and mRNA examined by
      immunohistochemistry and Northern blot analysis revealed a marked elevation in
      the cells cultured with the M-CM which was significantly reduced by TNF and IL-1
      antibodies. These data demonstrate that mononuclear cells can stimulate LA-4
      cells to express iNOS by releasing TNF and IL-1.

PMID- 9001324
TI  - Primary pulmonary hypertension, tissue plasminogen activator antibodies, and HLA
      DQ7.
AB  - Antibodies to fibrin-bound tissue plasminogen activator (tPA) have been found in
      autoimmune diseases with vascular injury, such as systemic lupus erythematosus
      and scleroderma. The purpose of this study was to determine whether patients with
      primary pulmonary hypertension (PPH) have an immunogenetically determined
      response to fibrin-bound tPA. Antibodies to fibrin-bound tPA were determined in
      three patient groups: 45 adults with PPH, 41 children with PPH, and 40 children
      with anatomically large congenital pulmonary to systemic communications
      (PHT+shunt). The frequencies of the HLA class II (DRB1,3,4,5, and -DQB1) alleles
      in these three patient groups were compared with those of 51 healthy Caucasian
      control subjects. Fibrin-bound tPA antibodies were found in four of 45 (9%)
      adults with PPH, four of 41 (10%) children with PPH, and one of 40 (2.5%)
      children with PHT-shunt. HLA class II typing, which was available for seven of
      nine Caucasians with fibrin-bound tPA antibodies, revealed that six of seven
      (86%) patients typed HLA-DQ7 (DQB1*0301) and one typed HLA-DQ6. The 86% frequency
      of HLA-DQ7 in the antibody positive patients was significant compared with the
      29% frequency in the healthy control subjects (p = 0.007, p corrected [pc] =
      0.05, OR = 14.4). Of interest, these antibody-positive patients, although lacking
      antiphospholipid antibodies, shared an amino acid epitope, common to HLA
      DQB1*06,07 and 08 subtypes, which was previously reported to be associated with
      the lupus anticoagulant. In conclusion, antibodies to fibrin-bound tPA and HLA
      DQ7, and possibly the same epitope associated with the lupus anticoagulant,
      defined a small subset of children and adults with PPH.

PMID- 9001325
TI  - Changes in breathing and ventilatory muscle recruitment patterns induced by lung
      volume reduction surgery.
AB  - Patients with chronic obstructive pulmonary disease have abnormal breathing and
      ventilatory muscle recruitment patterns at rest and during exercise, and these
      alterations may contribute to the limited exercise capacity seen in this disease.
      Lung volume reduction surgery (LVRS), a recently described treatment for
      emphysema, is reported to improve exercise performance. We studied the breathing
      and ventilatory muscle recruitment (VMR) patterns in eight patients with severe
      chronic obstructive lung disease (median FEV1 = 0.79 L, range 0.46 to 1.13 L) by
      measuring esophageal and gastric pressure measurements as well as tidal volumes
      (VT), respiratory rates (f), inspiratory (TI) and expiratory (TE) times, and
      watts at rest and during maximal exercise, before and 3 mo after lung volume
      reduction surgery. Maximal exercise capacity increased a median of 49% (median
      increase 17 watts, range 6 to 44 watts, p < 0.05) and maximal minute ventilation
      (VEmax) increased by a median of 22% (median increase 6.5 L/min, range 3 to 25
      L/min, p < 0.05). At isowatt exercise after surgery, VT increased 0.31 L (range
      0.07 to 0.69 L) and f decreased four breaths/min (range +0.5 to -15 breaths/min).
      Dyspnea scores as measured by a visual analog scale (VAS) decreased significantly
      at rest and at peak exercise after surgery. End-expiratory esophageal (Pes) and
      gastric (Pga) pressures at rest and at isowatt exercise decreased. A rightward
      shift in the slope of the Pes versus Pga plot was also observed suggesting
      increased use of the diaphragm after surgery. Our data indicate that LVRS
      improves the mechanics of breathing both at rest and during exercise.

PMID- 9001326
TI  - Spirometry values in stable lung transplant recipients.
AB  - To clarify the usefulness of spirometry to assess the function of the lung
      allograft post-transplant, we retrospectively reviewed 351 sequential spirometry
      measurements performed by 65 healthy recipients after the 80th postoperative day
      when the clinical evaluation and fiberoptic bronchoscopy with transbronchial
      biopsies and bronchoalveolar lavage excluded significant rejection or infection
      in the allograft. The mean coefficients of variation (CV) and significant values
      for change (SC) for the FVC, FEV1, and FEF25-75% were calculated according to the
      type of transplant procedure (heart-lung and double-lung [HL-DL] versus single
      lung [SL]), and to the time after transplant when the spirometry measurements
      were obtained < or = 1 yr versus > 1 yr). The SC for the FVC decreased with time
      after transplantation for both HL-DL (< or = 1 yr: 17% versus > 1 yr: 7%) and SL
      recipients (< or = 1 yr: 13% versus > 1 yr: 8%). The higher degree of variability
      within the first year was primarily due to increasing values especially in the HL
      DL recipients. The SC for the FEV1 also decreased over time for HL-DL recipients
      (< or = 1 yr: 18% versus > 1 yr: 9%) but was similar for SL recipients at both
      intervals (13%). Our results suggest that decreases of > or = 11% in FVC or 12%
      in FEV1 in HL-DL recipients and > or = 12% in FVC or 13% in FEV1 for SL
      recipients indicate a significant decrease in allograft function that may be due
      to infection or rejection.

PMID- 9001328
TI  - Acute eosinophilic pneumonia: histopathologic findings in nine patients.
AB  - Acute eosinophilic pneumonia is characterized by acute respiratory insufficiency,
      hypoxemia, fever, diffuse radiographic infiltrates, and eosinophilia in
      bronchoalveolar lavage fluid (BALF) or lung biopsies in the absence of infection,
      atopy, or asthma. A rapid response to corticosteroids is characteristic. We
      reviewed our experience with nine cases of acute lung disease with histologic
      features of acute and organizing diffuse alveolar damage and prominent
      interstitial and alveolar eosinophils in order to determine whether this
      pathology was characteristic of acute eosinophilic pneumonia. The mean age of the
      patients (four men and five women) was 53 yr (range: 33 to 71 yr). They presented
      with 2 to 21 d of dyspnea, cough, myalgias, and fever. All were hypoxic and had
      bilateral infiltrates on chest radiographs. Peripheral blood eosinophilia was
      present in four of eight patients (peripheral blood count unavailable for one
      patient). All patients were treated with high-dose corticosteroids with a mean
      time to symptomatic and radiographic improvement of 4 d. Seven of the nine
      patients enrolled in the study are alive without relapse; one patient has a mild
      deficit in diffusing capacity, and one patient died of a myocardial infarct while
      improving on therapy. The presence of eosinophils in cases of acute respiratory
      insufficiency due to diffuse alveolar damage (DAD) should suggest the diagnostic
      possibility of acute eosinophilic pneumonia. Acute eosinophilic pneumonia should
      be distinguished from other causes of DAD because of important differences in
      natural history.

PMID- 9001327
TI  - Intrapleural streptokinase versus urokinase in the treatment of complicated
      parapneumonic effusions: a prospective, double-blind study.
AB  - Intrapleural administration of fibrinolytics has been shown in small numbers of
      patients with complicated parapneumonic effusions (CPE) and pleural empyema to be
      effective and relatively safe. Although streptokinase (SK) is recommended as the
      fibrinolytic of choice, there are no comparative studies among fibrinolytics. We
      therefore compared the efficacy, safety, and the cost of treatment two of the
      most used thrombolytics, SK and urokinase (UK). Fifty consecutive patients with
      CPE or empyema were randomly allocated to receive either SK (25 patients) or UK,
      in a double-blind fashion. All patients had inadequate drainage through chest
      tube (< 70 ml/24 h). Both drugs were diluted in 100 ml normal saline and were
      infused intrapleurally through the chest tube in a daily dose of 250,000 IU of SK
      or 100,000 IU of UK. The chest tube was clamped for 3 h after instillation.
      Response was assessed by clinical outcome, fluid drainage, chest radiography,
      pleural ultrasound, and/or computed tomography. Clinical and radiologic
      improvement was noted in all but two patients in each group, who required
      surgical intervention. The mean volume drained during the first 24 h after
      instillation was significantly increased; 380 +/- 99 ml for the SK group (p <
      0.001) and 420.8 +/- 110 ml for the UK group (p < 0.001). The total volume (mean
      +/- SD) of fluid drained after treatment was 1,596 +/- 68 ml for the SK group,
      and 1,510 +/- 55 ml for the UK group (p > 0.05). The SK instillations (mean +/-
      SD) were 6 +/- 2.16 (range, 3 to 10) and those of UK 5.92 +/- 2.05 (range, 3 to
      8). High fever as adverse reaction to SK was observed in two patients. The total
      cost of the drug in the UK group was two times higher than that of SK ($180 +/-
      47 for SK and $320 +/- 123 for UK). The mean total hospital stay after beginning
      fibrinolytic therapy was 11.28 +/- 2.44 d (range, 7 to 15) for the SK group and
      10.48 +/- 2.53 d (range, 6 to 18) for the UK group (p = 0.32). We conclude that
      intrapleural SK or UK is an effective adjunct in the management of parapneumonic
      effusions and may reduce the need for surgery. UK could be the thrombolytic of
      choice given the potentially dangerous allergic reactions to SK and relatively
      little higher cost of UK.

PMID- 9001329
TI  - A dose-dependent inhibitory effect of cyclosporine A on obliterative
      bronchiolitis of rat tracheal allografts.
AB  - Inbred DA and WF rats were used as donors and recipients of heterotopic tracheal
      allografts. To investigate cellular and molecular mechanisms as well as
      inhibitory effects of differently acting immunosuppressive drugs on the
      development of obliterative bronchiolitis (OB), the recipient rats received
      either cyclosporine A (CsA; 1, 2, or 5 mg/kg/d), 15-deoxyspergualin (DSG; 1 or 2
      mg/kg/d), or mycophenolate mofetil (MMF; 20 or 40 mg/kg/d), or were left without
      immunosuppression. The grafts were removed at various time points for histology
      and immunohistochemistry. In tracheal allografts removed from nonimmunosuppressed
      animals, respiratory epithelium was replaced by cuboidal or squamous cell
      epithelium, with markedly enhanced expression of epithelial major
      histocompatibility class (MHC) Class II antigens at 3 d after transplantation.
      This was associated with a pronounced inflammatory episode and proliferation of T
      cells and macrophages, with the prominence of lymphoid activation markers, MHC
      Class II antigens and interleukin-2R (IL-2R). Later, total epithelial necrosis
      developed and intense proliferation of granulation tissue occluded the airway
      lumen producing a condition resembling OB in humans. In syngeneic tracheal
      grafts, no such changes could be observed. CsA decreased the development of OB in
      a dose-dependent fashion, in association with downregulation of epithelial MHC
      Class II antigen expression, IL-2R expression, and the infiltration of T cells.
      The new immunosuppressive drugs DSG (suppression of the monocyte/macrophage
      action and lymphocyte proliferation) and MMF (blocking of the de novo pathway of
      purine synthesis), in the dose range tested, showed no significant effect on the
      development of OB. These results suggest that an acute alloimmune response to
      airway targets, perhaps to epithelium, is the primary cause of OB, since CsA,
      with a nearly exclusive effect on the transcription of immune cytokines, entirely
      inhibited the generation of OB, and that preventive intervention for OB must
      occur early in the T-cell activation pathway.

PMID- 9001330
TI  - Surfactant dysfunction makes lungs vulnerable to repetitive collapse and
      reexpansion.
AB  - Reexpansion of collapsed lung creates intrapulmonary shear forces. In an earlier
      study we showed that application of a negative end-expiratory airway pressure
      (NEEP) to normal rabbit lungs in vivo produced tidal collapse and reexpansion
      with transient changes in compliance and gas exchange but no histologic damage.
      In the present study we examined NEEP in a model of surfactant perturbation
      produced by an inhaled aerosol of 2% and 5% dioctyl sodium sulfosuccinate (DOSS).
      DOSS increased alveolocapillary permeability without affecting compliance or
      oxygenation. Repeated collapse and reexpansion (RECOREX), caused by NEEP for 3 h
      was compared with ventilation with positive-end expiratory pressure (PEEP).
      Groups ventilated with PEEP maintained normal lung mechanics and morphology even
      if pretreated with DOSS. NEEP disturbed lung mechanics and gas exchange with
      persistent dose-related histologic damage in animals pretreated with DOSS. Lungs
      subjected to NEEP without DOSS had normal morphology. We conclude that
      perturbation of the surfactant system makes lungs vulnerable to injury by
      RECOREX. The combination of DOSS and NEEP might lead to leakage of plasma
      proteins into alveoli, causing inactivation of surfactants and increased shear
      forces with resulting lung damage. Similar mechanisms may accelerate lung damage
      in the respiratory distress syndrome.

PMID- 9001331
TI  - The incidence of false-positive cultures for Mycobacterium tuberculosis.
AB  - The frequency of false-positive cultures for Mycobacterium tuberculosis due to
      cross-contamination has been difficult to determine because of the lack of
      specific strain markers. Isolates collected prospectively over 5 yr from a
      municipal health department laboratory underwent DNA fingerprinting using the
      IS6110 and pTBN12 sequences. We reviewed the clinical and laboratory records of
      all isolates that had matching DNA fingerprints and were processed within 42 d of
      each other; 8 isolates were classified as probable or definite false-positives,
      representing 4.0% (8/199) of the culture-positive patients. A convenience sample
      of 42 isolates from three other mycobacterial laboratories also underwent DNA
      fingerprinting, and five (12%) were found to be definite or probable false
      positives. Cross-contamination during initial processing of specimens was the
      most common source of false-positive cultures. The source of cross-contamination
      for three false-positive cultures was a laboratory proficiency survey specimen
      containing strain H37Ra. Ten of the 13 patients were misdiagnosed as having
      tuberculosis, and seven received unnecessary multidrug treatment. Clinicians
      should be aware of the potential for false-positive cultures for M. tuberculosis,
      and mycobacteriology laboratories need to carefully review procedures to minimize
      this occurrence. DNA fingerprinting provides a valuable tool for the study of
      false-positive cultures.

PMID- 9001332
TI  - Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa.
AB  - We have studied the effect of salmeterol on both P. aeruginosa interactions with
      the mucosa of nasal turbinate organ cultures and on pyocyanin-induced (20
      microg/ml) and elastase-induced (100 microg/ml) damage to nasal epithelial cells.
      Organ cultures were exposed to salmeterol either by preincubation with 4 x 10(-7)
      M salmeterol for 30 min or by pipetting 20 microl of 4 x 10(-7) M salmeterol onto
      the organ culture surface immediately prior to bacterial inoculation. Infected
      organ cultures (8 h) had significantly (p < or = 0.01) increased epithelial
      damage, and P. aeruginosa was predominantly associated with damaged epithelium
      and mucus. Salmeterol significantly (p < or = 0.02) reduced epithelial damage
      caused by infection and the total number of adherent bacteria (p < or = 0.05),
      but bacterial distribution on the mucosa was unchanged. Nasal epithelial cells
      incubated with pyocyanin (20 microg/ml) or elastase (100 microg/ml) for 3 h had
      significantly (p < or = 0.05) increased cytoplasmic blebbing and mitochondrial
      damage versus control values. Elastase also significantly (p < or = 0.05)
      increased cell projection and reduced the level of ciliation. Cells preincubated
      with salmeterol (2 x 10(-7) M) showed a significant reduction in some features of
      cell damage caused by both toxins, which was inhibited by the beta2-adrenoceptor
      antagonist propranolol. Our results indicate that salmeterol reduces P.
      aeruginosa-induced damage to both organ culture and nasal epithelium.

PMID- 9001333
TI  - Effect of clarithromycin on lymphocytes in chronic respiratory Pseudomonas
      aeruginosa infection.
AB  - In a newly established murine model of chronic Pseudomonas aeruginosa respiratory
      infection mimicking diffuse panbronchiolitis (DPB), we investigated the effect of
      oral administration of clarithromycin on lymphocyte accumulation in the lung.
      Infection was produced by placement of a plastic tube precoated with P.
      aeruginosa in the bronchus. The number of bacteria on the tube was 6.25 +/- 0.22
      log10 colony-forming units (cfu)/ml. Viable bacteria were constantly isolated at
      10(5) to 10(6) cfu/specimen from the lungs for more than 1 yr. The
      histopathologic features resembled those of DPB consisting of massive
      accumulation of lymphocytes in the lung. The total number of pulmonary
      lymphocytes started to increase on Day 7, reaching a peak level within 12 d of
      intratracheal challenge. The number remained steady at that level for up to 120
      d. There was also a steady fall in the CD4+/CD8+ ratio in the lungs, commencing
      on Day 7 and persisting to Day 120. A 10-d course of oral clarithromycin (10
      mg/kg/d) from Day 7 resulted in a reduction of lymphocyte numbers to baseline
      level, although the dose did not influence the number of bacteria in the lungs.
      Treatment also increased the CD4+/CD8+ ratio to the baseline level from Day 7 to
      17. Our results were similar to those detected in bronchoalveolar lavage fluid of
      patients with DPB and suggest that the therapeutic benefits of clarithromycin are
      due to its anti-inflammatory properties rather than antimicrobial effect.

PMID- 9001334
TI  - Sensitization to Blomia tropicalis in patients with asthma and identification of
      allergen Blo t 5.
AB  - In tropical and subtropical regions of the world, allergens produced by Blomia
      tropicalis are an important cause of IgE-mediated sensitization among patients
      with asthma. We compared the relative importance of sensitization to the two mite
      species among asthma patients from Florida, Puerto Rico, and Brazil (n = 83), who
      were concurrently exposed to B. tropicalis and D. pteronyssinus, with patients
      from the United States and from the United Kingdom (n = 56) exposed to D.
      pteronyssinus. In addition, molecular cloning techniques were used to clone and
      express a major B. tropicalis allergen. There were significant differences
      between IgE antibody responses to B. tropicalis and D. pteronyssinus that were
      related to exposure: only 22% of patients exposed to both species had a high
      ratio (> 10) of IgE D. pteronyssinus:B. tropicalis, whereas 68% of patients
      exposed only to D. pteronyssinus had a ratio of > 10 (p < 0.001). A major 14-kD
      allergen (Blo t 5), cloned from a B. tropicalis cDNA library, showed 43% sequence
      homology to D. pteronyssinus Der p 5. Recombinant Blo t 5 produced in E. coli
      reacted with 45 to 69% of sera from B. tropicalis-allergic asthmatics and induced
      positive immediate skin tests at 10(-3) to 1 microg/ml. In vivo and in vitro
      comparisons of IgE responses to B. tropicalis, D. pteronyssinus, rBlo t 5, and
      rDer p 5, showed that B. tropicalis has unique allergens that cause specific IgE
      responses. The results suggest that B. tropicalis is an independent cause of
      sensitization and that use of recombinant Blo t 5 should lead to a better
      understanding of the role of B. tropicalis in causing asthma in tropical
      environments.

PMID- 9001335
TI  - Prednisone increases PGH-synthase 2 in atopic humans in vivo.
AB  - We compared the expression of prostaglandin H synthase-2 (PGHS-2, cyclooxygenase)
      message and protein in alveolar macrophages (AM) and blood monocytes (BM) from 20
      atopic subjects (AS) and nine control subjects (CS) at baseline and after 1 to 14
      d of oral administration of therapeutic doses of prednisone. At baseline, the
      amounts of PGHS-2 mRNA in AM and BM varied within a similar range among subjects
      from each group. PGHS-2 protein was present in AM and BM from most AS, but it was
      also present in CS. In AS, PGHS-2 mRNA and protein significantly increased after
      prednisone administration, whereas in CS PGHS-2 message and protein remained
      undetectable or, if present at baseline, was decreased after prednisone. Ex vivo
      both atopic and normal monocytes and macrophages exhibited the expected decrease
      in stimulated PGHS-2 mRNA with glucocorticoids. PGHS-1 expression was not altered
      by prednisone in either group. The differential regulation of the inducible PGHS
      isoform by prednisone may be mediated by effects on cytokine production in AS.

PMID- 9001336
TI  - Peripheral chemoreceptors in congenital central hypoventilation syndrome.
AB  - Congenital central hypoventilation syndrome (CCHS) is a rare disorder of unknown
      etiology, characterized by failure of the autonomic control of respiration. The
      primary defect is believed to involve central respiratory control; however, no
      specific lesion has been identified. We report two cases of CCHS (one female, 3
      mo of age and one male 2 yr of age) in which there was detailed examination of
      the neural, muscular, and chemoreceptor components of respiratory control.
      Although no specific abnormalities were identified in the central nervous system
      (CNS) or muscles of respiration, striking changes were observed in arterial
      chemoreceptors, carotid bodies (CB), and airway chemoreceptors, neuroepithelial
      bodies (NEB). In both cases, CB were small (< 50% of control), with a marked
      decrease in the number of glomus cells identified by immunostaining for tyrosine
      hydroxylase and serotonin. Ultrastructural analysis of glomus cells in Case 1
      showed a marked decrease in the frequency of dense core vesicles (< 20% of
      control), the storage site of amine and peptide neurotransmitters. Immunostaining
      for S100 protein, a marker of sustentacular or Type II cells, was increased up to
      twofold compared with controls. In the lung, the frequency and size of NEB
      immunostained for bombesin was increased twofold in both cases, suggesting
      compensatory hyperplasia of airway chemoreceptors. Since intact peripheral
      chemoreceptors are essential for respiratory control, especially the response to
      hypoxia, abnormalities in CB and NEB may contribute to the pathophysiology of
      CCHS and related conditions such as sudden infant death syndrome (SIDS).

PMID- 9001338
TI  - Pleural effusion due to herpes simplex type II infection in an immunocompromised
      host.
AB  - Pleural effusions caused by herpes simplex viruses are rare. We report a case of
      a young woman with acute lymphocytic leukemia (ALL) and prolonged neutropenia who
      developed pleural space infection with herpes simplex type II virus (HSV II), as
      confirmed by cytologic and microbiologic studies. We believe that this is the
      first report of a pleural effusion caused by HSV II, and suggest that this virus
      now be considered in the differential diagnosis of an unexplained exudative
      pleural effusion, especially in an immunocompromised host.

PMID- 9001337
TI  - Bronchial casts in children: a proposed classification based on nine cases and a
      review of the literature.
AB  - Bronchial casts are characterized by the formation of obstructive airway plugs
      that may be large enough to fill the branching pattern of an entire lung. The
      condition is rare but can occur at any age. Casts may be secondary to underlying
      diseases such as asthma and cystic fibrosis, but there are often no predisposing
      factors. There is no accepted classification system for bronchial casts; but only
      a confusion of descriptive terms such as mucoid impaction, fibrinous bronchitis,
      and pseudomembranous bronchitis. Based on a review of nine well-documented cases
      and the available literature, we have separated bronchial casts into two well
      defined groups: Type 1 (inflammatory), consisting of casts composed mainly of
      fibrin with a dense eosinophilic inflammatory infiltrate; and Type 2 (acellular),
      consisting of casts composed mainly of mucin with little or no cellular
      infiltrate and occurring only in children with congenital cyanotic heart disease.
      Acute mortality was high in both groups. Survivors of Type 1 casts seem to be
      well controlled with inhaled steroids. Optimal therapy for patients with Type 2
      casts is not clear; the prognosis probably depends on underlying cardiac status.
      We hope that this simple classification will provide a framework for further
      study of this obscure condition.

PMID- 9001339
TI  - Alveolar fluid glutathione is not reduced in asymptomatic HIV-seropositive
      subjects.
AB  - Glutathione is an important antioxidant tripeptide that is found in high
      concentrations in the epithelial lining fluid (ELF) of the lung. Previous
      investigators demonstrated a deficiency of glutathione (GSH) in the epithelial
      lining fluid of human immunodeficiency virus (HIV)-seropositive patients. The
      current investigation performed bronchoalveolar lavage (BAL) on 59 asymptomatic
      HIV-seropositive subjects (mean CD4: 365.9 +/- 31.2 cells/mm3) and 12 normal
      control subjects. The volume of ELF and the concentration of glutathione and
      oxidized glutathione were determined. The concentration of total GSH in ELF was
      not significantly different in HIV-seropositive individuals compared with normal
      subjects (628.1 +/- 63.9 microM versus 499.9 +/- 86.0 microM, p = 0.38). However,
      there was a significantly higher concentration of ELF GSH in HIV-seropositive
      cigarette smokers (n = 30) compared with nonsmokers (n = 29) (800.3 +/- 107.7
      microM versus 443.6 +/- 45.3 microM, p = 0.004). The percentage of total GSH in
      the oxidized form (GSSG) was similar in both the HIV-seropositive and the normal
      subject groups (3.4 +/- 0.3% versus 3.0 +/- 0.4%, p = 0.559). There were no
      significant correlations between ELF GSH or GSSG concentrations and age, CD4
      count, or pulmonary function. There was, however, a significant negative
      correlation between BAL lymphocyte percentage and GSH. The current study suggests
      that for those patients whose HIV infection is at a relatively early phase, the
      levels of GSH in the lung ELF are normal.

PMID- 9001340
TI  - Testing for human immunodeficiency virus infection among tuberculosis patients in
      Los Angeles.
AB  - To investigate patterns of testing for human immunodeficiency virus (HIV)
      infection in tuberculosis patients, we obtained data from the tuberculosis
      registry and from medical records of 500 tuberculosis patients in Los Angeles
      County. Sixty-three percent of tuberculosis patients were tested for HIV
      infection, and multivariate logistic regression analysis revealed that the
      likelihood of testing was significantly higher among males, persons between 20
      and 49 yr old, individuals with HIV risk factors, and patients treated by public
      health care providers. A minimum of 12% of the total sample, 2% of females, 2% of
      those outside the ages of 20 to 49, 7% of patients without recorded HIV risk
      factors, and 17% of patients treated by private practitioners were infected with
      HIV. These results suggest that health care providers, particularly private
      practitioners, do not follow national recommendations for universal HIV testing
      of tuberculosis patients. Instead, HIV testing is preferentially performed on
      patients perceived to be at high risk for HIV infection. Because HIV
      seroprevalence is at least 2 to 7% in "low-risk" groups, failure to test these
      patients may result in significant missed opportunities for diagnosis and
      treatment of HIV coinfection.

PMID- 9001341
TI  - The risk of asthma attributable to occupational exposures: a population-based
      study in Spain.

PMID- 9001342
TI  - Presence of human papillomavirus type 6f in tonsillar condyloma acuminatum and
      clinically normal tonsillar mucosa.
AB  - An attempt was made to detect human papillomavirus (HPV) in 8 cases of oral
      papilloma by Southern blot hybridization. HPV type 6 was identified in a case of
      tonsillar condyloma acuminatum, but neither HPV type 6 nor 11 was found in the 7
      other cases of squamous papilloma. The hybridization pattern of the HPV type 6
      DNA after digestion with restriction enzymes revealed that the HPV was of the 6f
      subtype. DNA samples isolated from the condyloma acuminatum, 3 peripheral
      specimens of clinically normal tonsillar mucosa, a swab sample and saliva from
      the male patient with this tonsillar condyloma acuminatum were examined further
      by polymerase chain reaction (PCR). HPV type 6 DNA was detected in the tonsillar
      condyloma acuminatum and the 3 specimens of clinically normal tonsillar mucosa,
      but no HPV type 6 DNA was detectable in the normal tonsillar mucosa by Southern
      blot hybridization using a whole HPV DNA probe. The presence of a small amount of
      HPV in clinically normal tissue detectable only by PCR suggests latent infection
      of peripheral tissues with HPV produced from the condyloma acuminatum. Although
      HPV type 6 DNA was not detectable in the swab and saliva samples of this single
      case, further study is necessary for the clinical application of preoperative
      virological diagnosis by PCR using these samples.

PMID- 9001343
TI  - Suppressed apoptotic induction in esophageal squamous cell carcinomas expressing
      extensive p53 protein.
AB  - p53 protein accumulation, thought to be caused by p53 gene mutation, is closely
      related to poor prognosis of patients with certain types of carcinomas. The
      progression of esophageal squamous cell carcinoma (SCC) is also strongly
      suspected to depend on the p53 tumor suppressor gene. Formalin-fixed, paraffin
      embedded sections were taken from 25 patients who underwent esophagectomy for
      SCC. Fourteen patients had no preoperative therapy (control group), while the
      other 11 patients received preoperative radiotherapy (radiation group). There was
      no difference in pathological TNM classification between the two groups. These
      sections were examined by immunostaining with monoclonal antibody PAb 1801 to
      determine the accumulation of p53 protein, and apoptotic frequency was determined
      by TdT mediated dUTP-biotin nick end-labeling (TUNEL). In the control group, well
      to moderately differentiated cases showed a significantly higher AI (apoptotic
      index which is the number of apoptotic cells among 1000 cancer cells. %0) (51.7+/
      83.4) than poorly differentiated cases (AI=1.3+/-1.0) (P<0.05). Similar results
      were obtained in the radiation group. The former group included 4 cases of p53
      grade 4 (p53 protein detected in over 70% of the tumor cells), and the latter
      included 2. Few apoptotic cells were observed in any of 6 tumor tissues. In each
      patient, tumor cells with accumulated p53 protein were very rare to be apoptotic.
      On the other hand, apoptosis was observed in tumor cells without p53 protein
      accumulation. Spontaneous apoptosis in esophageal SCC can be induced more easily
      in differentiated than in poorly differentiated cases. This tendency may be
      enhanced by preoperative radiotherapy. Extensive p53 protein may suppress
      apoptotic induction in esophageal squamous cell carcinomas.

PMID- 9001344
TI  - Prognostic significance of proliferating cell nuclear antigen (PCNA) in squamous
      cell carcinoma of the esophagus.
AB  - Proliferating cell nuclear antigen (PCNA) has been shown to be of prognostic
      significance in some gastrointestinal tumors. Immunohistochemical analysis was
      performed to determine whether PCNA is useful for predicting the outcome of
      patients with squamous cell carcinoma of the esophagus. Using a mouse monoclonal
      antibody, PC 10, the expression of PCNA was studied in resected squamous cell
      carcinomas of the esophagus from 59 patients who had undergone curative
      esophagectomy. None had received any preceding therapy. The proliferation rate
      was assessed in terms of the percentage of the PCNA-positive nuclear area
      relative to the total area of cancer nuclei using a cell analysis system (CAS).
      Clinicopathological variables including PCNA staining were assessed in relation
      to prognosis. Survival rate was obtained by the Kaplan-Meier method. The PCNA
      indices (percentage of the positive nuclear area) of the tumors varied from 4.4%
      to 96.2%. Among the clinicopathological variables, only tumor size (5 cm) and
      depth of invasion were correlated significantly with PCNA index (P<0.05).
      Microscopically, PCNA was stained in non-keratinized cells but not in keratinized
      cells. However the histological grade was not correlated with PCNA index. The
      survival rate was significantly worse in patients with high PCNA indices (> or =
      40%) than in those with low indices (<40%) (P<0.05). However, multivariate
      analysis revealed that PCNA index was not an independent prognostic factor.

PMID- 9001345
TI  - Immunohistochemical study of estradiol, epidermal growth factor, transforming
      growth factor alpha and epidermal growth factor receptor in endometrial
      neoplasia.
AB  - In a total of 113 cases of endometrial neoplasm, we studied the
      immunohistochemical expression of estradiol (E2), epidermal growth factor (EGF),
      transforming growth factor alpha (TGFalpha), and epidermal growth factor receptor
      (EGFR). Positive immunoreactivity of E2 was found in 61% of the neoplasms. E2
      immunoreactivity correlated well with high histologic grade and early clinical
      stage. Positive immunoreactivity for EGF or EGFR was found in 25.6% or 53.1% of
      the neoplasms, respectively. However, this was unrelated to histologic grade or
      clinical stage. On the other hand, TGFalpha immunoreactivity was found in 67% of
      endometrial neoplasias and was correlated with poor histologic grade and advanced
      stage. Contingency tables indicated a significant negative association between
      the status of E2 and that of TGFalpha. Simultaneous expression of E2, EGF and
      EGFR, or E2, TGFalpha and EGFR was found in 6.8% and 15.9% of endometrial
      carcinomas, respectively. These results suggest that a predominant number of
      endometrial carcinomas escape autocrine/paracrine growth regulation by EGF and E2
      or TGFalpha and E2, and that TGFalpha may be involved in the progression of
      endometrial carcinoma.

PMID- 9001346
TI  - Detection of K-ras point mutations in mesenteric venous blood from colorectal
      cancer patients by enriched polymerase chain reaction and single-strand
      conformation polymorphism analysis.
AB  - In order to confirm the presence of cancer cells in mesenteric venous blood and
      to examine their relationship with the occurrence of liver metastases, we
      attempted to detect K-ras codon 12 point mutations in perioperative mesenteric
      blood using enriched polymerase chain reaction and single-strand conformation
      polymorphism (PCR-SSCP) analysis in 25 patients with primary colorectal tumors
      carrying K-ras point mutations. Among these patients, three with synchronous
      liver metastases were included. The same K-ras point mutation (substitution of
      GAT for GGT) was detected in both the blood and the primary tumor in a Dukes' C
      patient. We confirmed this result by colony hybridization and estimated the tumor
      to-normal cell ratio to be 1:400. This patient has no liver metastases two years
      after surgery and her carcinoembryonic antigen (CEA) level remains normal. We
      demonstrated that considerable numbers of cancer cells can be found in mesenteric
      venous blood during colorectal cancer surgery. However, their potential role in
      the formation of liver metastases remains unclear.

PMID- 9001347
TI  - Evaluation of routine sonography for early detection of pancreatic cancer.
AB  - The diagnostic accuracy of routine abdominal sonography for the detection of
      pancreatic cancer was examined. During the one-year period of 1994, sonographic
      examination of the upper abdominal region was performed 12,761 times on a total
      of 9410 patients for the screening of abdominal disorders. In 655 cases (7%) part
      of the pancreas could not be observed. Based on the "Diagnostic criteria for
      pancreatic cancer" published by the Japanese Society of Ultrasound in Medicine,
      sonographic finding was evaluated to be positive for pancreatic tumor in a total
      of 411 cases. At the end of 1995, 51 patients were proven to have pancreatic
      cancer, and 45 of these cases were ductal adenocarcinoma. In 26 cases the tumor
      was surgically resected. Fifty cases were true sonographic positives and one was
      a false negative. The sensitivity, specificity, overall accuracy, and positive
      and negative predictive values of sonography for pancreatic cancer were 98.0%,
      95.9%, 95.9%, 12.2% and 100.0%, respectively. Among the 50 true positive cases,
      the tumor diameter was less than 1 cm in four (8%). In conclusion, the diagnostic
      accuracy of sonography for the detection of pancreatic cancer is sufficiently
      high. Therefore, a detailed study aimed at mass screening for pancreatic cancer
      using sonography as the main modality seems warranted as a countermeasure for the
      rapid increase of pancreatic cancer in Japan.

PMID- 9001348
TI  - Clinical usefulness of determining the rate of thermal clearance within heated
      tumors.
AB  - Between June 1987 and June 1988, 28 patients (28 tumors) with liver,
      retroperitoneal, intrapelvic, or superficial tumors were treated with
      hyperthermia combined with radiotherapy and/or chemotherapy. Hyperthermia was
      administered once or twice a week for 30-60 min per session, up to a total of 2
      11 sessions, with an 8-MHz RF capacitive heating device. Blood flow in the tumors
      was evaluated from the rate of thermal clearance (TCR) using the bio-heat
      transfer equation. The TCR was measured in the middle of the first heating
      session and at the end of the last heating session by turning off the output
      power of the heating device. For 9 patients, contrast-enhanced CT scans were
      taken and CT numbers at the centers of tumors were measured before and after the
      entire course of hyperthermia. Changes in TCR were closely related to average
      tumor center temperature, changes in CT number, and tumor response. When smaller
      and more superficial tumors were treated by hyperthermia combined with
      radiotherapy and/or chemotherapy that consisted of many heating sessions and
      during which a high average tumor center temperature was achieved, a better tumor
      response was obtained. The better the tumor response, the higher the local
      control rate became. The cause-specific survival rate of patients who achieved
      good tumor responses was higher than that of patients who showed poor tumor
      responses. Changes in TCR and CT number in heated tumors were useful and
      important indicators of tumor response to hyperthermia.

PMID- 9001349
TI  - Preoperative serum prostate-specific antigen, clinical stage and Gleason sum as
      basis for predicting final pathological stage in Japanese patients with prostate
      cancer.
AB  - By logistic regression analysis and log-likelihood ratio chi-square test, the
      usefulness of preoperative variables (prostate specific antigen [PSA], clinical
      stage and biopsy Gleason sum) for predicting the final pathological stage was
      assessed in 77 patients with clinically resectable prostate cancers.
      Pathologically, 32 (41.6%) had organ-confined disease. Extracapsular extension
      was found in 41 (53.2%), seminal vesicle involvement in 30 (39.0%), positive
      pelvic lymph nodes in 10 (13.0%) and a positive surgical margin in 27 (35.1%).
      Each preoperative variable was found to be significantly associated with the
      final pathological stage. Any combination of these variables was more predictive
      for extraprostatic disease, compared with each individual variable.
      Extraprostatic spread was found more frequently in patients with lower serum PSA
      in this Japanese elderly male population compared with North American males.
      These preoperative variables considered in combination may provide valuable
      information for management decisions related to prostate cancer. Serum PSA alone
      cannot reliably predict pathological stage on an individual basis except in
      patients with a PSA level of 20 ng/ml or greater. The high incidence of
      extraprostatic spread at intermediate PSA underscores the importance of selecting
      an ideal cutoff value for PSA-based screening in a Japanese male population.

PMID- 9001350
TI  - Prognostic factors and a predictive model of follicular lymphoma: a 25-year study
      at a single institution in Japan.
AB  - The incidence of follicular lymphoma in Japan is far lower than that in western
      countries, and no large-scale clinicopathologic studies on this neoplasm have
      been conducted in Japan. We reviewed histopathological specimens from 118 of 135
      patients who had been diagnosed as having follicular lymphoma between 1968 and
      1993. Prognostic factors influencing survival were analyzed using univariate and
      multivariate analyses. Factors that were independently significant upon
      multivariate analysis were incorporated into a predictive model. Ninety-three
      patients (78.8%) had a confirmed diagnosis of follicular lymphoma. Twenty-one of
      the remaining 25 patients were categorized as having other lymphoma subtypes, and
      four patients showed indefinite findings or those suggesting diseases other than
      lymphoma. Major characteristics of the 93 patients with follicular lymphoma were
      a median age of 53 years (20-85); 59 males (63%) and 34 females (37%); small
      cleaved cell type in 33 (35%), mixed cell type in 41 (44%) and large cell type in
      19 (20%); stage I/II in 41 (44%) and stage III/IV in 50 (54%). Overall survival
      was 71% at 5 years, 58% at 10 years, and 43% at 15 years with a median survival
      of 13.3 years. Multivariate analysis revealed that two variables, age (>60)
      (P=0.001) and the serum LDH level (>1 x normal value) (P=0.026), were unfavorably
      significant prognostic factors influencing survival. The predictive model using
      these two variables identified three risk groups with estimated five-year
      survival rates of 88.5%, 56.8%, and 31.5%. Age and serum LDH were significant
      predictors of survival in Japanese patients with follicular lymphoma. Our
      predictive model may provide a basis for future therapeutic trials against
      follicular lymphoma in Japan.

PMID- 9001351
TI  - Combination phase I/II study of irinotecan hydrochloride (CPT-11) and carboplatin
      in relapsed or refractory non-Hodgkin's lymphoma. CPT-11/Lymphoma Study Group.
AB  - Irinotecan hydrochloride (CPT-11) is a new derivative of camptothecin which
      inhibits topoisomerase I. Phase II studies have demonstrated that CPT-11 is
      active against a broad spectrum of neoplasms including intractable non-Hodgkin's
      lymphoma. An early phase II study in lymphoma suggested that a schedule of daily
      infusions of 40 mg/m2/day for three or five consecutive days is more effective
      than a single infusion of 200 mg/m2 every three to four weeks. Carboplatin is
      also an active agent against lymphoma, and preclinical studies have shown that
      CPT-11 and its active metabolite have a synergistic effect with platinum
      compounds. To evaluate the maximal tolerated dose (MTD) and the therapeutic
      efficacy of CPT-11 in combination with carboplatin in relapsed or refractory non
      Hodgkin's lymphoma, we conducted a combination phase I/II study. The starting
      dose of CPT-11 was 20 mg/m2/day (days 1 through 3 and 8 through 10), and dose
      escalations of 5 mg/m2/day increments were planned, with a fixed dose of
      carboplatin (300 mg/m2, day 1). Six of the eight patients receiving both agents
      at the starting dose level developed critical toxicities such as grade 4
      hematologic (neutropenia 6/8, thrombocytopenia 1/8) and grade 3 non-hematologic
      toxicities (diarrhea 2/8, transaminase elevation 1/8). Further dose escalation of
      CPT-11 was halted, and the starting doses were judged to be the MTDs. The
      response rate (25%, 2/8) to the combination of the MTDs was not superior to that
      of CPT-11 alone in a previous phase II study (38%, 26/69), and the MTD of CPT-11
      in combination with carboplatin was less than half the single-agent dose. We
      conclude that carboplatin is not recommendable for combination with CPT-11 in
      lymphoma patients. Other suitable agents for such a combination should be sought.

PMID- 9001352
TI  - Palliative therapy using polyurethane-covered self-expandable metallic stents for
      malignant esophageal strictures: experiences in six patients.
AB  - To evaluate the utility and limitations of palliative stenting with polyurethane
      covered self-expandable metallic stents, 6 patients (3 males and 3 females
      ranging in age from 58-85 [mean 72.1] years) with malignant esophageal strictures
      were treated with these stents between April 1993 and October 1995. Three had
      esophageal carcinoma, two had gastric carcinoma and one had lung carcinoma. Song
      type self-expandable metallic stents were inserted by intubation under local
      laryngeal anesthesia. A retriever was attached in 4 stents and an anti-reflux
      mechanism was attached in 2 stents placed over the esophagocardiac strictures.
      The stents were placed successfully in all patients, and no major complication
      related to intubation was encountered. All the stents fully expanded within 3
      days after insertion. The grade of dysphagia was improved in 5 (83%) of the 6
      patients. One stent was extracted using a retriever in one patient with no
      improvement. No reflux symptoms were observed in 2 patients whom received stents
      with an anti-reflux mechanism. No blockage of the stent due to food impaction or
      secondary stricture occurred in any patient during the observation period. One
      stent migrated into the stomach in one patient 27 days after insertion.
      Esophageal stenting with polyurethane-covered self-expandable metallic stents is
      a relatively safe and effective palliation for malignant esophageal strictures.

PMID- 9001353
TI  - Percutaneous transhepatic biliary drainage for the treatment of obstructive
      jaundice caused by metastases from nonbiliary and nonpancreatic cancers.
AB  - The usefulness of percutaneous transhepatic biliary drainage (PTBD) in the
      treatment of obstructive jaundice caused by metastases from nonbiliary and
      nonpancreatic cancers was evaluated. Eighteen patients underwent PTBD during a 3
      year period. The primary cancers were located in the stomach (nine cases), colon
      (four), lung (three), uterus (one), and breast (one). The causes of obstructive
      jaundice and bile duct strictures were investigated using both abdominal computed
      tomography and abdominal ultrasonography. The causes of obstructive jaundice, the
      usefulness of PTBD in terms of the relief of symptoms and laboratory data,
      survival after PTBD, and the relationship between patient characteristics and
      survival were evaluated. Obstructive jaundice was most often attributable to
      metastases to the lymph nodes (17 of 18 cases). One case was attributed to
      metastasis to the liver. PTBD decreased the jaundice and relieved the symptoms
      caused by biliary tract obstruction. Median survival after PTBD was 59 days.
      Patients whose performance status was 2 or less survived longer than those with a
      performance status of 3 or more (P=0.018). Furthermore, patients aged less than
      60 years tended to survive longer than those aged 60 or over (P=0.057). Our
      results suggest that PTBD is useful for relief of symptoms caused by obstructive
      jaundice in patients with nonbiliary and nonpancreatic cancers.

PMID- 9001354
TI  - A case of malignant pleural mesothelioma with metastasis to the orbit.
AB  - A 58-year-old woman with malignant mesothelioma metastatic to the orbit is
      reported. Malignant pleural mesothelioma was diagnosed by pleural biopsy. Marked
      reduction of pleural effusion was obtained with intrapleural interleukin-2
      therapy. Systemic chemotherapy failed to elicit a response after the first
      recurrence of the tumor. Multiple systemic metastasis, including metastasis to
      the orbit, developed and the patient died one year and 4 months after the initial
      diagnosis. Although malignant mesothelioma is known to spread hematogenously,
      sometimes producing brain metastasis, there have been few reports of orbital
      metastasis, and in fact the present report may be the first clinically documented
      account of its kind.

PMID- 9001355
TI  - A case of bone marrow recurrence from gastric carcinoma after a nine-year disease
      free interval.
AB  - We present a case of very late and unusual recurrence of gastric cancer. Nine
      years following total gastrectomy for gastric carcinoma, a 57-year-old man
      presented with disseminated intravascular coagulation associated with bone marrow
      recurrence. The primary tumor was a signet ring cell carcinoma invading the
      subserosal layer with lymph node metastasis. The patient was treated with
      sequential administration of methotrexate and 5-fluorouracil and went into
      remission. After treatment, he survived 10 months. Autopsy revealed diffuse bone
      marrow infiltration and distant lymph node metastasis with signet ring carcinoma
      cells.

PMID- 9001356
TI  - Preoperative intra-arterial infusion chemotherapy for invasive thymoma: a case
      report.
AB  - A 24-year-old man was diagnosed as having mixed-type thymoma by preoperative
      percutaneous needle biopsy. A chest computed tomogram showed a tumor measuring
      12x9 cm. Selective intra-arterial infusion chemotherapy was first selected
      because invasion to the superior vena cava was suspected. Bolus injection of 50
      mg/m2 cisplatin and 20 mg/m2 adriamycin was performed once into the right
      internal thoracic artery. The resulting decrease in tumor size was 81%. Neither
      complications due to the infusion procedure nor side effects due to the
      anticancer drugs were encountered. An extended thymectomy with partial resection
      of the mediastinal pleura was safely performed. The histological diagnosis of the
      resected tumor was thymic hyperplasia. The patient was transferred to a
      radiologist for additional radiotherapy. Selective intra-arterial infusion
      chemotherapy for invasive thymoma is an effective therapy, producing no
      significant side effects and allowing safe resection.

PMID- 9001357
TI  - Osteochondroma after total body irradiation in bone marrow transplant recipients:
      report of two cases.
AB  - We present two cases of osteochondroma after total body irradiation in bone
      marrow recipients, the first in a 6-year-old boy with juvenile chronic
      myelogenous leukemia and the second in a 13-year-old boy with acute myelogenous
      leukemia. The patients developed multiple osteochondromas three years and seven
      years, respectively, after 12 Gy of total body irradiation. Neither had a family
      history of hereditary multiple osteochondromatosis. A review of the English
      literature revealed only one report describing five cases of osteochondroma after
      12 Gy of total body irradiation in bone marrow transplant recipients.
      Osteochondroma should be considered as an additional adverse effect of total body
      irradiation.

PMID- 9001358
TI  - Successful radical surgery for an undifferentiated gallbladder carcinoma with
      lymph node metastases to the mesocolon.
AB  - We report successful radical systematic surgery for an undifferentiated
      gallbladder carcinoma with metastasis to the mesocolonic lymph nodes. The
      patient, a 70-year-old woman, was admitted with abdominal fullness and appetite
      loss. Imaging modalities revealed a 10-cm tumor originating from the gallbladder
      and infiltrating both the liver and transverse colon. As multiple mesocolonic
      lymph node metastasis was confirmed on laparotomy, right hemicolectomy with
      systematic lymph node dissection (D3 resection) was performed, in addition to
      extended cholecystectomy with partial resection of segments 4, 5 and 6 of the
      liver and distal gastrectomy. Histologically, the tumor was diagnosed as an
      undifferentiated carcinoma, and metastases were indentified in the mesocolonic
      lymph nodes (17/50 nodes) but not in the peri-gallbladder lymph nodes (0/16
      nodes). The patient has been recurrence-free for 4 years after the operation.
      This case illustrates that even if gallbladder cancer infiltrates into adjacent
      organs with regional lymph node metastasis, it is of value to perform radical
      surgery with systematic lymph node dissection for the involved organs.

PMID- 9001359
TI  - Colorectal cancer at the National Cancer Center Hospital: a prospective from the
      UK.

PMID- 9001360
TI  - Mitochondrial NADH- or NADPH-linked aquacobalamin reductase activity is low in
      human skin fibroblasts with defects in synthesis of cobalamin coenzymes.
AB  - Mammalian livers have been reported to contain NADH- and NADPH-linked
      aquacobalamin reductases, which are distributed in both mitochondria and
      microsomes. The four aquacobalamin reductase isozymes have been purified and
      characterized from rat liver. It is unclear which aquacobalamin reductase among
      the four reductase isozymes participates in the synthesis of cobalamin coenzymes.
      To clarify the physiological roles of the aquacobalamin reductase isozymes, human
      mutant fibroblasts (cblC and cblA cells) with defects in cobalamin reductases
      involved in the coenzyme synthesis were used. In the cblC cells, the activity of
      the mitochondrial NADH-linked aquacobalamin reductase was reduced significantly,
      compared with normal human fibroblasts but the mitochondrial NADPH-linked enzyme
      was not. The reduced specific activity of the NADH-linked enzyme was not due to
      reduction in levels of the enzyme, but in its affinity for NADH. Although there
      was not a significant difference in the mitochondrial NADH-linked enzyme activity
      between normal and cblA cells, the activity of the mitochondrial NADPH-linked
      enzyme was not detectable in the mutant cells. These results indicate that the
      defects in the mitochondrial NADH- and NADPH-linked aquacobalamin reductases
      underlie cblC and cblA disorders, respectively.

PMID- 9001361
TI  - Oleic acid incorporation protects cultured hamster fibroblasts from oxygen
      induced cytotoxicity.
AB  - The effects of oleic, linoleic and arachidonic acid on oxygen toxicity were
      evaluated in cultured hamster fibroblasts. Each fatty acid was incorporated
      separately using a protocol that resulted in dose-dependent increases in the
      respective cellular fatty acid content to as much as 20-fold greater than
      unsupplemented controls. Linoleic acid produced no changes in cell survival after
      48 h treatment with 95% oxygen, regardless of fatty acid content of the cells.
      Oleic acid incorporation resulted in a dose-dependent increase in cell survival
      at 48 h in 95% oxygen, whereas arachidonic acid incorporation resulted in a dose
      dependent decrease in cell survival at 48 h in 95% oxygen. No significant
      differences in amounts of linoleic or arachidonic acids were detected in control,
      oleic acid- enriched or linoleic acid-enriched cells during oxygen exposure. In
      cells enriched with arachidonic acid, exposure to oxygen significantly reduced
      the amounts of linoleic and arachidonic acid to 79 and 84%, respectively, of the
      amounts found in air-exposed cells. The results indicate that oleic acid
      incorporation into cells provides protection against 95% oxygen-induced
      cytotoxicity. In contrast, arachidonic acid incorporation led to sensitization of
      cells to 95% oxygen-induced cytotoxicity that was accompanied by a loss of
      polyunsaturated fatty acids. As a result, it would appear that in situations of
      increased oxidative stress, high monounsaturated fatty acid diets that increase
      cellular oleic acid content may provide a protective environment compared with
      high polyunsaturated fatty acid diets that increase cellular arachidonic acid
      content.

PMID- 9001363
TI  - Anthropometric, lifestyle and menstrual factors influencing size-adjusted bone
      mineral content in a multiethnic population of premenopausal women.
AB  - We report associations of anthropometric, lifestyle and menstrual characteristics
      with peak bone mass in a multiethnic population of premenopausal women, ages 25
      34 y. Four bone sites were examined: the spine, calcaneus, and distal and
      proximal radius. Body mass index (BMI) was positively associated with bone mass
      at the spine and calcaneus, the two most trabecular sites. The calcaneus, in
      addition, was positively associated with an index of calf muscle mass. The distal
      radius was associated with an arm muscle index, grip strength and the intensity
      of menstrual flow (light, moderate or heavy). Menstrual flow was also associated
      with spine bone mass in models not adjusted for BMI; light flow was an indicator
      of low distal radius or spine bone mass. We hypothesize that light flow may
      indicate a lack of regular ovulation. The cortical proximal radius was positively
      associated with milk consumption and height. The magnitude of associations varied
      by exposure and bone site. Among the strongest associations were BMI at the spine
      and calcaneus (4 and 7% differences in bone mass per standard deviation), and
      menstrual flow at the distal radius (a 7% difference between light and heavy
      menstrual flow). Ethnicity was not statistically significant in multivariable
      models at any of the four bone sites. However, the prevalence of exposures
      associated with bone mass varied substantially among the ethnic groups. Ethnic
      differences in bone mass may have derived indirectly through differences in
      exposure histories. Other influences of skeletal development may also occur
      indirectly. Sports activity during adolescence, for instance, was not an
      independent predictor of bone mass, but sports activity was associated with both
      strength and muscle mass. Our results suggest that many factors influence peak
      bone mass, and that the factors vary in importance by skeletal region, possibly
      related to bone composition and the local intensity of exposure.

PMID- 9001362
TI  - Vitamin A deficiency has different effects on immunoglobulin A production and
      transport during influenza A infection in BALB/c mice.
AB  - We examined the effect of advanced vitamin A deficiency (serum retinol < or =
      0.35 micromol/L, with weight gain significantly lower than in controls with free
      access to food) on the secretory immunoglobulin A (IgA) response to a mild, upper
      respiratory tract infection with influenza A virus in BALB/c mice. Mice fed a
      vitamin A-deficient or control diet were infected intranasally at 11 to 12 wk of
      age. The influenza-specific salivary IgA response was lower in the vitamin A
      deficient mice (0.11 +/- 0.13% of total IgA 4 wk after infection) than in
      controls with free access to food (2.73 +/- 1.86%, P < 0.0001). In a separate
      experiment, the response of vitamin A-deficient mice (0.42 +/- 1.51%) was also
      lower than that of pair-fed controls (3.43 +/- 4.76%, P < 0.0001). In addition,
      fewer influenza A-specific IgA-secreting plasma cells were found in the salivary
      glands of vitamin A-deficient mice (geometric mean 3.0%) than in controls with
      free access to food or in pair-fed controls (geometric mean 8.7%, P < 0.0001).
      Although the pathogen-specific IgA response was decreased, vitamin A-deficient
      mice had a significantly higher concentration of total salivary IgA (31.9 +/-
      15.9 mg/L) than did the pair-fed controls (14.3 +/- 8.4 mg/L, P < 0.0001).
      Northern blot analysis of salivary gland RNA revealed that these vitamin A
      deficient mice also had greater levels of mRNA of the polymeric immunoglobulin
      receptor (pIgR), which transports IgA across mucosal surfaces (plgR: beta-actin
      mRNA ratio = 7.8 +/- 0.8), than did pair-fed control mice (3.7 +/- 0.4, P =
      0.0001). These data demonstrate that vitamin A deficiency has contrasting effects
      on the secretory IgA response to influenza infection, with a principal effect
      being a decrease in the pathogen-specific response.

PMID- 9001364
TI  - Catch-up growth in children fed a macrobiotic diet in early childhood.
AB  - To study the relationship between diet and growth, a longitudinal anthropometric
      study was conducted in a Dutch population consuming a macrobiotic diet.
      Measurements (anthropometry and food habit questionnaire) were taken in 1985 (0-7
      y), 1987, and in 1993 (7-16 y, n = 209). Z-scores were calculated for
      anthropometric measures and changes expressed as the differences between 1993 and
      the mean of 1985 and 1987. Analysis indicated significant (P < 0.002) catch-up in
      height [(mean Z-score +/-sEM) +0.59 +/- 0.071 and arm circumference (+0.34 +/-
      0.09) for age (boys and girls combined). In 1993, both girls and boys were still
      significantly (P < 0.05) below the reference for height and sum of four skinfolds
      for age, and girls were below reference for weight-for-height and arm
      circumference for age. In girls, multiple regression analyses showed a
      significant positive effect of the consumption frequency of dairy products on
      catch-up growth in height, weight and arm circumference, after adjustment for
      menarche, age, and baseline height, weight and arm circumference (P < 0.05). The
      addition of moderate amounts of dairy products to a vegan type of diet improved
      growth of children, especially girls.

PMID- 9001365
TI  - Increased energy intake in pregnant smokers does not prevent human fetal growth
      retardation.
AB  - A retrospective cohort study of 729 smoking and 610 nonsmoking pregnant women
      participating in the Prince Edward Island Prenatal Nutritional Counselling
      Program (1979-1989) was undertaken to study whether lower energy intake results
      in lower maternal weight gain and/or a higher rate of small-for-gestational-age
      infants (SGA) among smokers. A second objective was to quantify, using
      etiological fractions, the independent contributions of cigarette smoking,
      maternal pregravid underweight and low pregnancy weight gain to the risk of SGA.
      Measurements of maternal pregravid weight, height, pregnancy weight gain, smoking
      status, physical activity, energy intake by a series of 3-d food records
      throughout the duration of pregnancy, and infant birth weight were collected for
      women with uncomplicated pregnancies resulting in full-term singleton infants.
      Multiple linear regression analyses were performed to predict the effect of
      smoking on maternal energy intake, weight gain and infant birth weight. The
      independent contributions of smoking, pregravid underweight and low pregnancy
      weight gain to the risk of SGA were determined using logistic regression
      analysis. Smoking was independently associated with a higher energy intake [+702
      kJ/d (+168 kcal/d)] but with lower maternal weight gain (-2.16 kg) and infant
      birth weight (-205 g). Dietary energy intake was positively associated with only
      a small increment in birth weight [5.9 g per 418 kJ (100 kcal)]. The etiologic
      fraction for SGA attributable to smoking was 30.8%, pregravid underweight 16.7%,
      and low gestational weight gain 15.3%. We conclude that the important negative
      effect of smoking on retarding fetal growth cannot be adequately mitigated by
      simply increasing energy intake.

PMID- 9001366
TI  - Body image concepts differ by age and sex in an Ojibway-Cree community in Canada.
AB  - Community-based studies of body image concepts can be useful for developing
      health interventions to prevent obesity-related diseases such as diabetes and
      cardiovascular disease in specific populations. First Nations peoples, in
      particular, face increased obesity-related health problems as a result of
      acculturative changes in diet and activity. This study examined body shape
      perception in an Ojibway-Cree community in Northern Ontario, Canada. A set of
      figure outline drawings ranging from very thin to very obese were used to examine
      perceived body shape, body shape satisfaction and ideals of healthiness across
      sex and age groups. Overall, only 16% of the population were satisfied with their
      current body shape. People with a higher body mass index (BMI) were less
      satisfied with their bodies and thought they were less healthy than people with a
      lower BMI. While females had a significantly greater BMI than males, males and
      females did not differ significantly in perception of current body shape. On the
      other hand, females desired relatively smaller body shapes than males (P < 0.05).
      Older people chose significantly larger healthy body shapes than did younger
      people (P < 0.05). Differences between our results and those reported for Anglo
      populations indicate that while both groups prefer body shapes smaller than those
      they have currently, the Ojibway-Cree tend to prefer relatively larger body
      shapes. Knowledge of age and sex-related patterns of body image concepts in
      communities can assist in the design of obesity-reducing interventions targeting
      specific groups.

PMID- 9001367
TI  - Dietary intake of fat, fiber and other nutrients is related to the use of vitamin
      and mineral supplements in the United States: the 1992 National Health Interview
      Survey.
AB  - Supplement intake is hypothesized to increase the risk of some diseases while
      decreasing the risk of others. Both diet and lifestyle behaviors, however, may be
      associated with supplement use and confound observed associations. Nutrient
      intake from a food frequency questionnaire, demographic characteristics and
      lifestyle among supplement users and nonusers were examined in 11,643 adults who
      participated in the 1992 National Health Interview Survey Epidemiology
      Supplement. Forty-six percent reported taking a supplement in the past year; 24%
      reported daily use. Daily use was highest among women, whites, those 75 y of age
      or older, those at or above the poverty level, those with more than 12 y of
      education, former smokers, and light drinkers consuming less than one alcoholic
      beverage per week. When controlled for sociodemographic factors, smoking status
      and drinking habits, there were no significant (P < 0.01) differences in dietary
      nutrient intake between daily and occasional supplement users. Compared with
      those of nonusers, diets of vitamin supplement users were lower (P < 0.001) in
      fat and higher in fiber and vitamins A and C for both men and women and higher in
      vitamin E and calcium for women only. In general, diet, demographic and lifestyle
      characteristics of supplement users are typical of patterns associated with low
      risk of chronic disease.

PMID- 9001368
TI  - Stunting is associated with overweight in children of four nations that are
      undergoing the nutrition transition.
AB  - A higher risk of obesity in stunted children has been described in Hispanic
      American, Jamaican and Andean populations, but little systematic exploration has
      been done concerning this area in nutrition. This paper examines the relationship
      between stunting and overweight status for children aged 3-6 and 7-9 y in
      nationally representative surveys in Russia, Brazil, and the Republic of South
      Africa and a large nationwide survey in China. Using identical cut-offs for body
      mass index, the prevalence of child overweight in these countries ranges from
      10.5 to 25.6% (based on the 85th percentile); recent NHANES III results indicate
      that this prevalence is around 22% in the U.S. Stunting is also common in the
      surveyed countries affecting 9.2-30.6% of all children. Our results showed a
      significant association between stunting and overweight status in children of all
      countries. The income-adjusted risk ratios of being overweight for a stunted
      child ranged from 1.7 to 7.8. Clearly, there is an important association between
      stunting and high weight-for-height in a variety of ethnic environmental and
      social backgrounds. Although the underlying mechanisms remain unexplored, this
      association has serious public health implications particularly for lower income
      countries. As these countries enter the nutrition transition experiencing large
      changes in dietary and activity patterns, they may face, among other problems,
      additional difficulties in their fight against obesity.

PMID- 9001369
TI  - Early childhood supplementation does not benefit the long-term growth of stunted
      children in Jamaica.
AB  - The long-term benefits of early childhood supplementation and the extent to which
      catch-up growth occurs following linear growth retardation remain controversial.
      Stunted children (height-for-age < -2 SD of NCHS references, n = 122) recruited
      from a survey of poor neighborhoods in Kingston, Jamaica, participated in a 2-yr
      randomized, controlled trial of supplementation beginning at ages 9-24 mo. A
      group of 32 non-stunted children from the same neighborhoods was also followed.
      Four years after the intervention ended, when children were 7 to 8 y old, there
      were no effects of supplementation on any anthropometric measure. From the end of
      the trial until follow-up, the children who had been supplemented gained 1.2 cm
      less (P < 0.05) than the non-supplemented children, approximately the same amount
      as they had gained during the trial compared with the non-supplemented children.
      After adjustment for regression to the mean, the height-for-age of stunted
      children (supplemented and non-supplemented combined) increased from enrollment
      to follow-up by 0.31 Z-score (95% CI 0.17, 0.46). The height-for-age of the non
      stunted children also increased (0.96 Z-score; 95% CI 0.70, 1.22). Our results
      suggest that some catch-up growth is possible even when children remain in poor
      environments. Long-term benefits of supplementation to growth may not be achieved
      when intervention begins after age 12 mo in children who have already become
      undernourished.

PMID- 9001370
TI  - Dietary intake pattern relates to plasma folate and homocysteine concentrations
      in the Framingham Heart Study.
AB  - We examined the relationship between intake of food group (and supplement)
      sources of folate and plasma folate and homocysteine concentrations among 885
      elderly subjects in the Framingham Heart Study. Dietary data were collected by
      food-frequency questionnaire, and blood samples analyzed for folate and
      homocysteine concentrations. Top contributors to total folate intake were ranked.
      Mean folate intake, plasma folate and homocysteine concentrations were estimated
      for users vs. non-users of supplements, and key foods--those which both
      contribute to total folate intake and are known to be good sources of folate--and
      examined statistically with adjustment for age, gender and total energy intake.
      Plasma folate and homocysteine concentrations were also determined by quintile of
      intake frequency for breakfast cereals and for fruits and vegetables. Plasma
      folate was significantly greater and homocysteine lower in women than in men.
      Despite somewhat greater plasma folate concentrations with age, homocysteine was
      significantly higher in those over 80 y of age than in younger subjects. Major
      contributors to folate intake were cold breakfast cereals (13.3%), multivitamins
      (12.8%) and orange juice (12.4%). Users of supplements, breakfast cereals, or
      green leafy vegetables had significantly greater plasma folate and lower
      homocysteine levels than non-users. Plasma folate concentration was also greater
      in those who drank orange juice. We identified clear dose-response relationships
      for both plasma folate and homocysteine with increased quintile of breakfast
      cereal and of fruit and vegetable use. Frequent consumption of these foods is
      associated with higher folate and lower homocysteine concentrations.

PMID- 9001371
TI  - Supplementation with an algae source of docosahexaenoic acid increases (n-3)
      fatty acid status and alters selected risk factors for heart disease in
      vegetarian subjects.
AB  - The purpose of this double-blind study was to investigate the influence of
      dietary supplementation with an algae source of docosahexaenoic acid [DHA; 22:6(n
      3)], devoid of any eicosapentaenoic acid [EPA; 20:5(n-3)], on serum/platelet DHA
      status, the estimated retroconversion of DHA to EPA, and risk factors for heart
      disease in vegetarian subjects. Healthy vegetarians (12 male, 12 female) consumed
      nine capsules daily of either DHA (1.62 g/d) or corn oil for 6 wk. Consumption of
      DHA capsules increased DHA levels in serum phospholipid by 246% (from 2.4 to 8.3
      g/100 g fatty acids) and in platelet phospholipid by 225% (from 1.2 to 3.9 g/100
      g fatty acids). EPA levels increased in serum phospholipid by 117% (from 0.57 to
      1.3 g/100 g fatty acids) and in platelet phospholipid by 176% (0.21 to 0.58 g/100
      g fatty acids) via metabolic retroconversion; the estimated extent of DHA
      retroconversion to EPA was 11.3 and 12.0%, based on the serum and platelet
      analyses, respectively. Arachidonic acid [AA; 20:4(n-6)] levels in serum and
      platelet phospholipids decreased moderately during the trial period (DHA group)
      as did both docosapentaenoic acids [22:5(n-6) and 22:5(n-3)]. Although no
      significant changes were found in the total and LDL-cholesterol levels with DHA
      supplementation, the total cholesterol:HDL-cholesterol ratio showed a moderate
      decrease over time as did the LDL-cholesterol:HDL-cholesterol ratio and serum
      triglyceride concentrations. DHA supplementation did not alter the various
      thrombogenic factors measured. In conclusion, DHA supplementation markedly
      enhanced the DHA status (of serum and platelets), provided for the formation of
      substantial EPA, and lowered the total and LDL-cholesterol:HDL-cholesterol
      ratios.

PMID- 9001372
TI  - Dietary essential fatty acid deficiency differentially affects tissues of rats.
AB  - Quantitative variations of polyunsaturated fatty acids (PUFA) were studied in
      various tissues: red blood cells (RBC), hepatic microsomes, kidney, skeletal
      muscle and heart of young rats fed either a control diet (n = 7) or an essential
      fatty acid (EFA)-deficient diet (n = 7). After 4 wk, the EFA-[deficient rats had
      significantly lower proportions of (n-6) and (n-3) fatty acids in RBC, hepatic
      microsomes and kidney than the control group. Paradoxically, normal proportions
      of arachidonic acid [20:4(n-6)] and 5,8,11,14,17-eicosapentaenoic acid [20:5(n
      3)] were retained in heart and skeletal muscle despite generally lower
      proportions of the precursors, 18:2(n-6) and 18:3(n-3). Moreover, absolute levels
      of 20:4(n-6) and 20:5(n-3) in skeletal muscle of the EFA deficient group were
      significantly higher than in controls and 22:5(n-3) and 22:6(n-3) levels were
      comparable. This suggests that fatty acid proportions alone, without any
      consideration of long-chain polyunsaturated fatty acid quantities, may not
      reflect the (n-6) and (n-3) PUFA status of individual tissues. This study
      indicates that diet-[induced changes in the PUFA composition of RBC, which are
      often used in clinical investigations, do not fully reflect the changes in the
      fatty acid composition of organs, and that individual tissues respond differently
      to EFA deficiency. The conservation of proportional and absolute levels of 20:5(n
      3) and 20:4(n-6), and the decrease in the more unsaturated homologues in the
      heart, suggest that this organ may avidly retain 20:5(n-3) and 20:4(n-6) in order
      to maintain eicosanoid production.

PMID- 9001373
TI  - An extract of soy flour influences serum cholesterol and thyroid hormones in rats
      and hamsters.
AB  - The effects of an ethanol-acetone extract from soy flour on serum lipids and
      thyroid hormones were studied in rats and hamsters. In Study 1, male Sprague
      Dawley rats were fed diets containing protein from ethanol-acetone extracted
      isolated soy protein (ISP-), nonextracted ISP (ISP), casein (casein-), or casein
      to which 0.36 mg ethanol-acetone extract/g protein was added (casein+). Rats fed
      either ISP-containing diet had lower serum total cholesterol concentrations
      compared with those fed either casein diet (P < 0.05). Lower serum LDL
      cholesterol concentrations were present in rats fed either ISP-containing diet
      and in those fed casein+ compared with those fed casein- (P < 0.05). Adding the
      extract to casein (casein+) produced higher serum thyroxine concentration and
      free thyroxine indices compared with all other groups (P < 0.05). In Study 2,
      male Golden Syrian hamsters were fed experimental diets containing protein from
      ISP, ISP with added ethanol-acetone extract (0.36 mg extract/g protein; ISP+),
      casein-, casein+ (0.36 mg extract/g protein), or casein with twice the level of
      extract (0.72 mg/g protein; casein++). Lower serum total cholesterol and LDL (LDL
      + VLDL + IDL) cholesterol concentrations were observed in hamsters fed ISP, ISP+
      or casein+ compared with those fed casein- (P < 0.05). Addition of the extract at
      higher levels to casein (casein++) did not lower serum lipids relative to those
      fed casein-. Serum thyroxine concentration and the free thyroxine index were
      greater in both ISP groups as well as in hamsters fed casein++ compared with
      those fed casein- or casein+ (P < 0.05). In conclusion, both studies show that
      protein from soybeans decreases serum total and LDL cholesterol while the effects
      on thyroxine are different in rats and hamsters. It is also apparent that the
      ethanol-acetone extract of soy flour produces changes in serum cholesterol,
      particularly in the LDL fraction in both species.

PMID- 9001374
TI  - Extrusion and boiling improve rat body weight gain and plasma cholesterol
      lowering ability of peas and chickpeas.
AB  - This study investigated the effect of feeding peas (Pisum sativum) and chickpeas
      (Cicer arietinum) processed by boiling or extrusion on growth performance, plasma
      cholesterol concentrations and organ weights of rats. Casein was used as the
      protein source in the control diets. Complementarity of wheat and legumes on
      protein quality was also evaluated. Boiled or extruded legumes significantly
      increased body weight gain (BWG) of rats but not protein efficiency ratio (PER)
      when compared with raw legumes. Rats fed processed chickpeas and those fed casein
      had similar BWG, and both groups had greater BWG than rats fed peas. Extruded
      wheat combined with peas or chickpeas increased sulfur amino acid (SAA) levels in
      the diets and significantly improved BWG and PER of rats compared with those fed
      sucrose as an energy source. There was a linear correlation between the SAA to
      dietary protein ratio and BWG of rats (r = 0.902, P < 0.014), indicating that SAA
      are the limiting amino acids in legumes. Plasma cholesterol concentrations were
      lower in rats fed legumes than in those fed casein. Cholesterol-lowering ability
      was affected by processing method, with extrusion being most effective for peas;
      boiling and extrusion were equally effective for chickpeas. Raw legume feeding
      resulted in greater pancreatic and small intestine weight relative to body
      weight. Chickpea fed rats had lower spleen, thymus and liver relative weights and
      higher cecum and colon relative weights than rats fed casein. There were no
      differences in growth, PER, organ relative weight or plasma cholesterol
      concentration between rats fed extruded legumes and those fed boiled legumes,
      suggesting that extrusion improves nutritional value of these legumes to the same
      extent as the traditional boiling method.

PMID- 9001375
TI  - Antihypertensive peptides are present in aorta after oral administration of sour
      milk containing these peptides to spontaneously hypertensive rats.
AB  - Absorption of inhibitory peptides to angiotensin I-converting enzyme, L-valyl-L
      prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline, was studied in spontaneously
      hypertensive rats and normotensive Wistar-Kyoto rats after an oral administration
      of Calpis sour milk, which contains these peptides. Six hours after the
      administration of Calpis sour milk or saline to spontaneously hypertensive rats
      or normotensive Wistar-Kyoto rats, the blood pressure was measured and rats were
      killed. Abdominal aorta, lung, kidney, heart and brain were excised, homogenized
      and solubilized by detergent treatments. Angiotensin I-converting enzyme activity
      in the solubilized fractions from the abdominal aorta was significantly lower in
      spontaneously hypertensive rats given the sour milk than in the rats given
      saline. L-Valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline were
      detected by HPLC in the heat-treated solubilized fraction from the abdominal
      aorta of spontaneously hypertensive rats given the sour milk. In contrast, the
      tripeptides were not detected in rats given saline, or in normotensive Wistar
      Kyoto rats given the sour milk or saline. These data suggest that L-valyl-L
      prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline in the Calpis sour milk are
      absorbed directly without being decomposed by digestive enzymes, reach the
      abdominal aorta, inhibit the angiotensin I-converting enzyme, and show
      antihypertensive effects in spontaneously hypertensive rats.

PMID- 9001376
TI  - Stable isotope model for assessing production of short chain fatty acids from
      colon-derived sugar: application in pigs.
AB  - Sugar reaching the colon because of intestinal maldigestion or malabsorption may
      be fermented to acetate and other short-chain fatty acids, resulting in
      stimulation of colonic water absorption and cell proliferation. To explore this
      phenomenon in more detail, we have developed a stable isotope model for
      estimating the fraction of colon-derived glucose or lactose that is fermented to
      acetate, propionate and butyrate. In an initial application of the model, [d3]
      acetate and either [1-(13)C]-glucose or [D-1-(13)C]-lactose were infused into the
      cecum or colon of piglets, and plateau plasma acetate enrichment was monitored in
      the carotid artery. In acutely anesthetized piglets, the fractions of glucose and
      lactose fermented to acetate were 17.0 and 20.0%, respectively. In a chronically
      catheterized piglet, fermentation was higher (34.2%). When conducted in
      chronically catheterized animals or via a colostomy or ileostomy in infants, this
      model may be used to determine how age, previous surgery or antibiotic therapy
      affects the efficiency of colonic assimilation of carbohydrate.

PMID- 9001377
TI  - Formyltetrahydrofolates associated with mitochondria have longer polyglutamate
      chains than the methyltetrahydrofolates associated with cytoplasm in rat brain.
AB  - The subcellular distribution of folate coenzymes in the brain is unknown. Brain
      folate concentrations are low and hence require a sensitive assay to determine
      the subcellular distribution. Rat brain was fractionated by differential
      centrifugation into cytoplasmic, mitochondrial and crude synaptosomal fractions.
      The compositions of the folate pools in these subcellular fractions were
      determined by differential conversion of one-carbon forms enzymatically to 5,10
      methylenetetrahydrofolate (5,10CH2H4PteGlu(n)) followed by reaction of the
      5,10CH2H4PteGlu(n) with thymidylate synthetase and [3H]fluorodeoxyuridylate to
      form ternary complexes, which were then separated as a function of polyglutamate
      chain length by isoelectric focusing, visualized by fluorography and quantified
      by densitometry. The distribution of the pteridine derivatives in brain was very
      similar to the distribution of these derivatives in liver. Cytoplasm contained
      primarily 5-methyltetrahydropteroylpolyglutamates with smaller amounts of
      unsubstituted tetrahydropteroylpolyglutamates, whereas mitochondria contained
      approximately equal concentrations of unsubstituted and formyl-substituted
      tetrahydropteroylpolyglutamates. The subcellular distribution of polyglutamate
      derivatives in brain, however, was different from that in liver. In the brain,
      the mitochondrial folates exhibited longer polyglutamate chains than did the
      cytoplasmic folates, a pattern opposite to that in the liver. Whereas the brain
      cytoplasmic pteroylpolyglutamates were primarily penta and hexa glutamates, the
      brain mitochondrial pteroylpolyglutamates were primarily hexa and hepta
      glutamates. The brain also contained small but measurable levels of oxidized
      folates, which were seen in crude synaptosomal fractions but not in cytoplasmic
      or mitochondrial fractions.

PMID- 9001378
TI  - Food intake is inversely correlated with central nervous system histamine
      receptor (H1) concentrations in male Sprague-Dawley rats fed normal, low protein,
      low energy or poor quality protein diets.
AB  - The reported studies were designed to examine relationships between whole-brain
      histamine receptors (H1) and food intake in male Sprague-Dawley rats. Three
      different experiments were conducted. In each experiment, control rats were fed
      normal protein (25 g casein/100 g food) and normal metabolizable energy (16.21
      kJ/100 g food) diets. Feeding low protein diets (1 g casein/100 g food) elevated
      central H1 receptor concentrations (P < 0.0027) and reduced voluntary food intake
      (P < 0.007) compared with normal diets. Feeding low energy diets lowered H1
      receptor concentrations (P < 0.0089) and increased voluntary food intake (P <
      0.0012). Low quality protein diets also affected the central nervous
      histaminergic system. Whole-brain H1 receptor concentrations were significantly
      higher for rats fed low quality protein (25 g gelatin/100 g food) compared with
      rats fed casein (P < 0.0001). Rats fed medium quality protein (25 g wheat
      gluten/100 g food) or low quality protein ate significantly less food (P <
      0.0001). In all experiments, dietary manipulation affected central histamine
      receptors. Elevated concentrations of H1 receptors were associated with a
      decrease in food intake whereas lowered concentrations of H1 receptors were
      associated with an increase in food intake (P < 0.001). The results of these
      experiments support the hypothesis that central histamine H1 receptor
      concentrations in male rats are inversely correlated with voluntary food intake
      and affected by dietary composition.

PMID- 9001379
TI  - Efficiency of lysine or threonine retention in growing rats fed diets limiting in
      either lysine or threonine.
AB  - Over a 21-d experiment, the efficiency of lysine and threonine retention was
      determined in 80 male Sprague-Dawley rats (65.9 +/- 0.3 g, means +/- SE) fed
      purified diets containing an amino acid mix limiting in either lysine or
      threonine. With additional increments of the first limiting amino acid, lysine
      concentration in total body protein (g/16 g N) increased (P < 0.01) in rats fed
      lysine-limiting diets but, when fed threonine-limiting diets, lysine
      concentration in body protein first increased and then decreased (P < 0.01). As
      increments of the first limiting amino acid were added, the threonine
      concentration in total body protein increased then decreased when both lysine- (P
      < 0.01) and threonine- (P < 0.06) limiting diets were fed. Lysine and threonine
      retention were calculated based on comparative slaughter. Sixteen rats were
      killed on d 0 to estimate the grams of amino acid in the body. Retention
      responses were analyzed using a logistic equation in which lysine or threonine
      intake was used to predict retention. The maximum marginal efficiency (dr/dI,
      retention/intake) was observed at <40% of maximum retention. For lysine
      retention, it was 81% when lysine was limiting and 70% when threonine was
      limiting. For threonine retention, it was 58% when threonine was limiting and 49%
      when lysine was limiting. The maximum cumulative efficiency (retention adjusted
      for maintenance relative to cumulative intake) for lysine retention was 62% when
      lysine was limiting or 58% when threonine was limiting. For threonine retention,
      it was 51% when threonine was limiting and 35% when lysine was limiting. Thus,
      amino acid concentration in body protein is not constant, and amino acids are
      used with higher efficiency when first limiting.

PMID- 9001380
TI  - Bioavailability for humans of deuterium-labeled monoglutamyl and polyglutamyl
      folates is affected by selected foods.
AB  - Dietary folate exists mainly as polyglutamyl forms that require deconjugation by
      Zn-dependent pteroylpolyglutamate hydrolase prior to intestinal absorption.
      Because deconjugation by pteroylpolyglutamate hydrolase is an essential step in
      the absorption of dietary polyglutamyl folates, factors influencing the
      deconjugation process may affect folate bioavailability. This study was conducted
      to evaluate in vivo the bioavailability of [2H4]folic acid (d4-PteGlu1) and [2H2]
      pteroylhexaglutamate (d2-PteGlu6) administered in solution in water or citrate
      buffer or added to selected foods using a single-dose, dual-label protocol. In
      each of six trials, healthy men (n = 7) were given a single oral dose of d2
      PteGlu6 and d4-PteGlu1 (677 nmol of each form) blended into orange juice,
      tomatoes, lima beans, 52 mmol/L citrate (pH 4.1), or water as the control. Urine
      was collected for 48 h and the isotopic labeling of urinary folates used as
      criteria of the relative bioavailability of administered PteGlu1 and PteGlu6.
      Urinary excretion of d4-folates and d2-folates derived from the respective oral
      doses did not differ from the control in any treatment within the statistical
      power of this protocol. High relative bioavailability of the polyglutamyl folate
      was reflected by ratios of urinary d2/d4 folates of approximately 1.0 for
      control, tomato, lima bean and citrate buffer trials, whereas the ratio of
      urinary d2/d4 folates when subjects consumed orange juice was approximately 33%
      less than the control ratio (P < 0.05). These findings suggest that the
      bioavailability of polyglutamyl folates in orange juice would be partially
      incomplete. However, this would be compensated by the high total folate
      concentration of orange juice. The relation of these findings to endogenous
      dietary folates requires further investigation.

PMID- 9001381
TI  - Fatty acid composition of erythrocyte membranes affects iron absorption in rats.
AB  - We studied the influence of the fatty acid composition of three different diets
      on iron absorption in relation to the lipid peroxidation of the erythrocyte
      membranes. After weaning, three groups of rats were fed isoenergetic semipurified
      diets for 16 wk: control diet (containing canola oil and peanut oil), tripalmitin
      diet (a saturated fatty acid diet) and a sardine oil diet rich in polyunsaturated
      fatty acids. Eight rats from each group were administered 59FeSO4 by gastric
      intubation for ferrokinetic studies, and six rats from each group were used for
      several analyses in blood, liver, spleen and erythrocytes. Results obtained from
      59Fe eliminated in feces and 59Fe present in plasma, both calculated by the area
      under the curve and from maximum concentration in plasma, indicated that the
      sardine oil diet induced higher iron absorption than the control diet. The lipid
      peroxidation of erythrocyte membranes in rats fed sardine oil was higher than
      that in control rats due to high membrane's (n-3) polyunsaturated fatty acid
      content and low alpha-tocopherol level. The 59Fe in liver and spleen of rats fed
      the sardine oil diet was higher than in rats fed the control diet, and 59Fe was
      diverted to erythrocytes to a greater extent than in rats fed the control diet
      due to their reduced life-span. The sardine oil diet, by lessening alpha
      tocopherol and raising the degree of lipid peroxidation in erythrocytes, augments
      iron absorption, whereas the tripalmitin diet, by protecting erythrocyte
      membranes from lipid peroxidation, leads to a lower rate of iron absorption.

PMID- 9001382
TI  - Ferrous iron uptake but not transfer is down-regulated in Caco-2 cells grown in
      high iron serum-free medium.
AB  - Caco-2 cells in culture provide an attractive model for the study of human iron
      absorption. Because iron status has a marked effect on human iron absorption, we
      devised serum-free growth conditions that allow manipulation of Caco-2 cell iron
      stores while maintaining growth. Caco-2 cells were cultured in serum-free media
      containing 0-20 micromol/L added iron. Intracellular ferritin, measured by
      radioimmunoassay, increased 100-fold with the addition of 20 micromol/L iron to
      the serum-free growth medium. Iron uptake and transfer across Caco-2 cell
      monolayers were measured from balanced salt solutions of ferrous and ferric forms
      of iron. Uptake from ferrous, but not ferric, iron was inversely related to cell
      ferritin concentration and culture medium iron concentration. Kinetic analysis of
      uptake data from solutions of ferrous and ferric iron revealed saturable and
      nonsaturable components for ferrous iron, but only a nonsaturable component for
      ferric iron. Uptake by the nonsaturable pathway was not affected by cell ferritin
      concentration for either form of iron. Maximal uptake from a ferrous iron
      solution via the saturable pathway was nearly 100% greater in cells cultured
      under low compared with high iron conditions. Iron transfer across Caco-2
      monolayers was not proportional to iron uptake, but was related to monolayer
      permeability. Iron uptake by Caco-2 cells was a reliable indicator of relative
      iron availability. We observed no difference in iron transfer that was related to
      the iron status of the cell monolayer. The lack of this effect suggests that this
      model may be inadequate for studies of iron transfer.

PMID- 9001383
TI  - Gender affects rats' central nervous system histaminergic responses to dietary
      manipulation.
AB  - The histaminergic system (histamine and its H1-receptor) of the central nervous
      system has been implicated in control of food intake. The reported studies were
      designed to examine the effects of food restriction and very low (1%) protein
      diets on central nervous system H1-receptors in male and female rats. In a series
      of experiments, groups of rats were freely fed a 25% protein diet, a 1% protein
      diet, or fed the 25% protein diet at 4 g/100 g body weight for 14-20 d. When
      freely fed 25% protein diets, females had higher whole-brain H1-receptor binding
      than males on d 1 (female 122.36 +/- 4.53 and male 65.78 +/- 3.82 pmol/g protein;
      P < 0.001). Changing diets affected central H1-receptor binding in both males and
      females (P < 0.003). When rats were fed both restricted levels of food and 1%
      protein diets, the receptor binding of males increased by d 5 whereas that of
      females decreased by d 5 (P < 0.001). When fed 1% protein diets, females had
      decreased H1-receptor binding (98.4 +/- 2.38 pmol/g protein) and that in males
      increased to 119.81 +/- 5.09 pmol/g protein. After 15 d, females had eaten
      significantly more food than males: females 166 +/- 4.9 g, males 124 +/- 1.9 g
      (P< 0.0007). Males had a significantly greater weight loss than females: males 
      28.8 +/- 2.6 g, females -17.08 +/- 0.97 g (P < 0.0007). When fed restricted
      diets, females had decreased H1-receptor binding (93.81 +/- 5.58 pmol/g) whereas
      binding in males increased to 111.27 +/- 8.55 pmol/g. Preliminary saturation
      binding studies indicated that restricted food intake lowered receptor density
      (females consuming 25% protein: 715 +/- 30 pmol/g protein; female restricted: 467
      +/- 28 pmol/g protein, P < 0.05), while 1% protein increased receptor
      sensitivity, i.e., lowered KD (males consuming 25% protein: 15.3 +/- 1.8 nmol;
      males fed low protein: 2.8 +/- 0.27 nmol). This study suggests that dietary
      manipulation affects central H1-receptor binding in a gender-specific manner,
      thereby modulating central histaminergic activity during food or protein deficit.

PMID- 9001384
TI  - Acute-phase protein synthesis in rats is influenced by alterations in plasma and
      muscle free amino acid pools related to lower plasma volume following trauma.

PMID- 9001385
TI  - The MHC-encoded TAP1/LMP2 bidirectional promoter is down-regulated in highly
      oncogenic adenovirus type 12 transformed cells.
AB  - Cells transformed by human adenovirus 12 (Ad12) exhibit extremely low surface
      levels of MHC class I molecules and contain reduced levels of class I heavy chain
      mRNAs. We report that levels of MHC-encoded TAP1 and LMP2 mRNAs are also down
      regulated in Ad12-transformed rat cells, and that transcription of rat TAP1 and
      LMP2 transcripts is directed from a 564 bp intergenic region which is
      significantly less active in Ad12-transformed cells compared to those transformed
      with Ad5. Our results suggest that, in common with MHC class I gene expression,
      TAP1 and LMP2 gene expression is reduced mainly at the level of transcription in
      Ad12-transformed cells.

PMID- 9001386
TI  - Inhibition of phorbol ester-stimulated phospholipase D activity by chronic
      tamoxifen treatment in breast cancer cells.
AB  - We have shown that in an estrogen receptor-negative multidrug-resistant subline
      of MCF-7 human breast carcinoma cells longer-term (24 h), but not shorter-term
      (30 min), treatments with clinically relevant (2-5 microM) concentrations of
      tamoxifen (TAM) inhibited phorbol ester-stimulated phospholipase D (PLD) activity
      by 50-80%. TAM caused these inhibitory effects without inducing membrane
      translocation or down-regulation of protein kinase C-alpha, the major mediator of
      phorbol ester effects on PLD activation. The results raise the possibility that
      prolonged inhibition of the protein kinase C-alpha-regulated PLD system may
      contribute to the cytotoxic effects of tamoxifen in estrogen receptor-negative
      breast cancer cells.

PMID- 9001387
TI  - Purification of IpaC, a protein involved in entry of Shigella flexneri into
      epithelial cells and characterization of its interaction with lipid membranes.
AB  - Entry of Shigella flexneri into epithelial cells and lysis of the phagosome
      involve the secreted IpaA-D proteins. A complex containing IpaC and IpaB is able
      to promote uptake of inert particles by epithelial cells. This suggested that Ipa
      proteins, either individually or as a complex, might interact with the cell
      membrane. We have purified IpaC and demonstrated its interaction with lipid
      vesicles. This interaction is modulated by the pH, which might be relevant to the
      dual role of Ipa proteins, in induction of membrane ruffles upon entry and lysis
      of the endosome membrane thereafter.

PMID- 9001388
TI  - Site-specific introduction of an electroactive label into a non-electroactive
      enzyme (beta-lactamase I).
AB  - A cysteine residue was introduced close to the active site of beta-lactamase I by
      site-directed mutagenesis to replace tyrosine-105 and was subsequently modified
      with an electroactive SH-specific reagent, N-(2-ferrocene-ethyl)maleimide. The
      resulting modified enzyme became electroactive, showing good quasireversible
      electrochemistry which was characteristic of the attached ferrocene moiety while
      retaining its specific enzymatic activity. In the presence of a suicide
      substrate, 6beta-iodopenicillanic acid, the redox potential shifted +20 mV
      suggesting that the label was sensitive to changes in the active site of the
      enzyme.

PMID- 9001389
TI  - Clavanins, alpha-helical antimicrobial peptides from tunicate hemocytes.
AB  - Hemocytes from the invertebrate Styela clava, a solitary tunicate, contained a
      family of four alpha-helical antimicrobial peptides that were purified, sequenced
      and named clavanins A, B, C and D. Each clavanin contained 23 amino acid residues
      and was C-terminally amidated. The tunicate peptides resembled magainins in size,
      primary sequence and antibacterial activity. Synthetic clavanin A was prepared
      and displayed comparable antimicrobial activity to magainins and cecropins. The
      presence of alpha-helical antimicrobial peptides in the hemocytes of a
      urochordate suggests that such peptides are primeval effectors of innate immunity
      in the vertebrate lineage.

PMID- 9001390
TI  - Osmosignalling in C6 glioma cells.
AB  - The influence of aniso-osmolarity on the activity of the MAP kinases Erk-1 and
      Erk-2 was studied in C6 glioma cells. Hypo-osmotic treatment (205 mosmol/l) led
      to an increased activity of Erk-1 and Erk-2 within 3 min, which became maximal at
      10 min and returned to basal level within 120 min. In contrast, Erk activity was
      reduced under hyper-osmotic conditions (405 mosmol/l), compared to the normo
      osmotic control (305 mosmol/l). Erk activation was accompanied by a mobility
      shift of Raf-1. Hypo-osmotic exposure increased the cytosolic Ca2+ concentration
      ([Ca2+]i). Absence of extracellular Ca2+ largely abolished the [Ca2+]i response
      to hypo-osmolarity, whereas Erk activation following hypo-osmotic stimulation
      remained unaffected, suggesting a Ca2+ independence of the osmosignalling pathway
      to the MAP kinases. Both the Ca2+ response as well as the Erk activation
      following hypo-osmotic exposure were maintained in the presence of the
      phospholipase C inhibitor U73122. Application of 8-CPT cAMP,
      forskolin/isobutylmethylxanthine or isoproterenol blocked Erk activation
      following hypo-osmotic treatment of the cells, suggesting a role of the Ras/Raf
      pathway upstream from Erk-1 and Erk-2. Protein kinase C (PKC) is unlikely to play
      a role in the hypo-osmolarity- induced signalling towards MAP kinases, as
      revealed by inhibition of PKC with Go6850. Inhibition of pertussis- or cholera
      toxin-sensitive G-proteins as well as inhibition of tyrosine kinases with
      genistein and of PI3 kinase by wortmannin had no effect on the Erk response to
      hypo-osmolarity. It is concluded that osmosignalling in C6 glioma cells differs
      upstream of the MAP kinases from that observed in primary rat astrocytes, H4IIE
      rat hepatoma cells and isolated rat hepatocytes.

PMID- 9001391
TI  - ESTs reveal a multigene family for plant defensins in Arabidopsis thaliana.
AB  - Plant defensins, formerly named gamma-thionins, are a group of small, cysteine
      rich, basic, and antimicrobial plant proteins. Random sequencing of expressed
      sequence tags (ESTs) in Arabidopsis thaliana has revealed several different plant
      defensin genes in this plant species which can be grouped into two subfamilies.
      We have used one EST of each subfamily to study the expression of the
      corresponding genes in A. thaliana. Pdf2.3 is constitutively expressed in
      seedlings, rosettes, flowers, and siliques and is not inducible in seedlings
      either by methyl jasmonate, salicylate, ethephon, and silver nitrate or by
      several different phytopathogenic fungi. The expression of a second gene, Pdf1.2,
      is in untreated plants only detectable in rosettes. In seedlings, it is inducible
      by methyl jasmonate, silver nitrate, and different phytopathogenic fungi, notably
      Fusarium oxysporum f. sp. matthiolae. The regulation of Pdf1.2 resembles that of
      the pathogen-inducible thionin gene Thi2.1.

PMID- 9001392
TI  - A flexible lid controls access to the active site in 1,3,8-trihydroxynaphthalene
      reductase.
AB  - The crystal structures of apo-1,3,8-trihydroxynaphthalene reductase from
      Magnaporthe grisea and a binary complex of the enzyme with NADPH have been
      determined to 2.8 A resolution. In both cases, the overall structure is preserved
      compared to the structure of the ternary complex of the enzyme with NADPH and an
      active site inhibitor. No electron density for the helix-loop-helix region
      comprising residues 214-244 is observed indicating structural disorder in this
      part of the apoenzyme and the binary complex. In the ternary complex, this region
      is in contact with NADPH and the inhibitor and closes off the active site. The
      observed increase in flexibility in the absence of the inhibitor indicates that
      this region acts as a lid which closes the active site upon binding of the
      inhibitor and, possibly the substrate, 1,3,8-trihydroxynaphthalene.

PMID- 9001393
TI  - Co-elevation of brain natriuretic peptide and proprotein-processing endoprotease
      furin after myocardial infarction in rats.
AB  - We investigated the expression of the yeast Kex2 family endoproteases furin and
      PACE4, and brain natriuretic peptide (BNP) in the atrium and ventricle after
      infarction as well as the conversion of the BNP precursor gammaBNP to BNP-45. In
      a rat heart failure model, plasma BNP rose in two phases--first at day 3, and
      again at day 14. BNP mRNA, as measured by Northern blot analysis, increased
      strongly at day 3, then at days 14 and 28 less strongly in the atrium, and in the
      ventricle it increased weakly at day 3, then strongly at days 14 and 28. Furin
      mRNA showed the same pattern of expression as that of BNP message, whereas PACE4
      message stayed unchanged after the infarction. Both furin and BNP were
      immunostained in the myocardium adjacent to the infarcted tissue. We suggest that
      after myocardial infarction, furin is co-expressed with BNP in both the atrium
      and ventricle, and that furin may be responsible for the conversion of gammaBNP
      to BNP-45.

PMID- 9001394
TI  - Structure and distribution of a broadly expressed atypical sodium channel.
AB  - A cDNA clone isolated from a rat dorsal root ganglion library encodes a 195 kDa
      voltage-gated sodium channel-like protein (SCL-11) with homology to the mouse
      (87%) and human (72%) atypical Na+ channels and rat partial clone NaG (98%). Two
      dominant mRNAs of 4.5 and 7 kb are expressed. The transcripts are present in
      lung, Schwann cells, pituitary and tissues containing smooth muscle cells. No
      functional channels could be detected on oocyte injection with cRNA, consistent
      with the absence of structural features necessary for voltage-gated sodium
      channel activity.

PMID- 9001395
TI  - Biochemical characterization of Pkn2, a protein Ser/Thr kinase from Myxococcus
      xanthus, a Gram-negative developmental bacterium.
AB  - Pkn2, a protein Ser/Thr kinase, from the developmental bacterium Myxococcus
      xanthus was expressed under a T7 promoter in Escherichia coli and purified.
      Purified Pkn2 retained the autophosphorylation activity with the Km value of 177
      microM for ATP and 73 nmol/min/mg for Vmax. The optimum pH and temperature were
      determined to be 7.5 and 35 degrees C, respectively. The autophosphorylation
      activity was inhibited by staurosporine with the IC50 value of 400 nM while H-7
      and genistein had little effect on this kinase. Pkn2 appears to be unique for its
      higher manganese dependence. This is the first biochemical characterization of
      the prokaryotic protein Ser/Thr kinase.

PMID- 9001396
TI  - Preferential condensation of SAR-DNA by histone H1 and its SPKK containing
      octapeptide repeat motif.
AB  - Linker histone H1 binds preferentially the scaffold associated region (SAR) DNA
      elements that contain characteristic oligo dA x dT tracts. In the present study,
      we have compared the condensation brought about by histone H1 of a SAR DNA
      fragment in the histone spacer region of Drosophila melanogaster with that of a
      random DNA (pBR322 EcoRI-SalI) fragment by circular dichroism spectroscopy. The
      condensation of the SAR DNA fragment by histone H1 is 3-4-fold higher than that
      of the random DNA fragment. A 16-mer peptide, ATPKKSTKKTPKKAKK, the sequence that
      is present in the C-terminus of histone Hld, which has recently been shown to
      possess DNA and chromatin condensing properties, also condenses the SAR DNA
      fragment preferentially in a highly cooperative manner. We have proposed a model
      for the dynamics of chromatin structure involving histone H1-SAR DNA interaction
      through SPKK containing peptide motifs and its competition by AT-hook peptides
      present in the nonhistone chromosomal proteins like HMG-I and HMG-Y.

PMID- 9001397
TI  - Block of ShakerB K+ channels by Pi1, a novel class of scorpion toxin.
AB  - Here we describe the basic features of the interaction of K+ channels with Pi1, a
      recently described 35 amino acid scorpion toxin, which has four disulfide bridges
      instead of the three commonly found in all the other known scorpion toxins. We
      found that: (a) Pi1 blocks ShakerB from the outside with a 1:1 stoichiometry, and
      a Kd of 32 nM in zero external [K+]; (b) extracellular K+, Rb+ and Cs+ but not
      NH4+ ions strongly impede (destabilize) the block by this toxin; interestingly
      (c) the destabilizing binding of K+, Rb+, and Cs+ is described by a Hill
      coefficient n > 1; (d) external K+ is more effective than internal K+ to reduce
      the block by Pi1.

PMID- 9001398
TI  - The potato leafroll virus 17K movement protein is phosphorylated by a membrane
      associated protein kinase from potato with biochemical features of protein kinase
      C.
AB  - The 17 kDa protein (pr17), the phloem-limited movement protein (MP) of potato
      leafroll luteovirus (PLRV), is associated with membranous structures and
      localized to plasmodesmata [Tacke et al. (1993) Virology 197, 274-282; Schmitz,
      J. (1995) Ph.D. Thesis, University of Cologne]. In planta the protein is
      predominantly present in its phosphorylated form, but it is rapidly
      dephosphorylated during isolation under native conditions. In an effort to
      examine the nature of the protein kinase(s) involved in the phosphorylation
      reaction, pr17 deletion mutants were expressed as fusion proteins in a bacterial
      expression vector system and tested for their ability to be phosphorylated by
      potato membrane preparations as well as by commercially available kinases. A
      fusion protein containing the nucleic acid-binding, basic, C-proximal domain
      (pr17C1) was identified to be phosphorylated by a Ca2+- and phospholipid
      dependent, membrane-associated protein kinase. This protein kinase activity was
      inhibited by the addition of (19-36) protein kinase C (PKC) inhibitory peptide,
      known to be a highly specific inhibitor of mammalian PKC. Moreover, also the
      mammalian PKC from rat was able to phosphorylate pr17 in vitro. The results
      suggest that phosphorylation of pr17 takes place at membranous structures,
      possibly at the deltoid plasmodesmata connecting the sieve cell-companion cell
      complex of the phloem, by the activity of PKC-related, membrane-associated
      protein kinase activity.

PMID- 9001399
TI  - Identification of Asp804 and Asp808 as Na+ and K+ coordinating residues in alpha
      subunit of renal Na,K-ATPase.
AB  - Mutations to Asp804 and Asp808 in the alpha-subunit almost abolish Na,K-ATPase
      activity, but high-affinity binding of [3H]ATP or [3H]ouabain at equilibrium and
      E1-E2 transitions are preserved. Titration of K+-ion displacement of [3H]ATP or
      [3H]ouabain shows that the mutations interfere with occlusion of K+ in the E2[2K]
      conformation. Reduced phosphorylation levels or affinities for Na+ in presence of
      oligomycin indicate that Asp804 and Asp808 also contribute to coordination of Na+
      in the E1P[3Na] form. Demonstration of alternate interactions of Na+ or K+ with
      Asp804 and Asp808 support the notion of cation binding in a ping-pong sequence in
      catalytic models of Na,K-pumping.

PMID- 9001400
TI  - Identification and expression of a variant isoform of the levocabastine-sensitive
      neurotensin receptor in the mouse central nervous system.
AB  - This work describes the molecular cloning of a variant isoform of the low
      affinity levocabastine-sensitive neurotensin receptor isolated from mouse brain.
      Although the corresponding mRNA encodes for a 282 amino acid protein unable to
      bind neurotensin after transient transfection in COS-7 cells, this non-functional
      neurotensin receptor is expressed in cerebral neocortex, cerebellum, olfactory
      bulb, striatum and hypothalamus with a level similar to that of the full-length
      low-affinity neurotensin receptor. By contrast, this receptor form is very weakly
      expressed in mesencephalon and absent in the pituitary, but is the major product
      in the spinal cord.

PMID- 9001401
TI  - Cloning, expression and CNS distribution of Kv4.3, an A-type K+ channel alpha
      subunit.
AB  - A full-length K+ channel cDNA of Kv4.3, with an open reading frame of 611 amino
      acids, was isolated from rat hippocampus. Functional expression of Kv4.3 cDNA in
      Xenopus oocytes revealed an A-type K+ channel. In the central nervous system,
      Kv4.3 is most prominently expressed in the retrosplenial cortex, medial habenula,
      anterior thalamus, hippocampus, cerebellum, as well as lateral geniculate and
      superior colliculus, which are important for vision. The abundant expression of
      Kv4.3 in many CNS neurons supports its important role as a major component of
      subthreshold A currents in the control of action potentials and thus neuronal
      excitability.

PMID- 9001402
TI  - Isolation and characterization of the bioactive circulating human parathyroid
      hormone, hPTH-1-37.
AB  - The occurrence of hPTH-1-37 as the native bioactive circulating form of PTH-1-84
      has now been obtained using a specific purification procedure for circulating
      parathyroid hormone, which involves a newly developed immunoenzymetric assay for
      N-terminally intact hPTH. In combination with two different methods of mass
      spectrometry, the molecular weight of the isolated immunoreactive peptide was
      shown to be 4401 Da, which corresponds to hPTH-1-37. Synthetic hPTH-1-37 material
      was tested in the chick bioassay and produced a clearcut increase in serum
      calcium concentration. We conclude that hPTH-1-37 is the native bioactive
      fragment of hPTH-1-84 in circulation.

PMID- 9001403
TI  - Cysteine-rich regions of protein kinase Cdelta are functionally non-equivalent.
      Differences between cysteine-rich regions of non-calcium-dependent protein kinase
      Cdelta and calcium-dependent protein kinase Cgamma.
AB  - Regulatory domain elements of the non-calcium-dependent protein kinase Cdelta
      (nPKCdelta), including either or both of the cysteine-rich regions Cys1(delta)
      and Cys2(delta), were expressed as fusion proteins with glutathione-S-transferase
      and characterized using liposomal or mixed micellar phorbol ester binding assays.
      Fusion proteins containing Cys2(delta) bound phorbol-12,13-dibutyrate (PDBu)
      efficiently in the assay employing phosphatidylserine (PS) vesicles, while no
      significant binding was seen for proteins containing only Cys1(delta). Likewise,
      in mixed micellar assays, fusion proteins with Cys2(delta) bound PDBu with high
      affinity (Kd: 14-37 nM) and to significant stoichiometric levels (0.23-0.66
      mol/mol), but no binding could be detected for proteins with Cys1(delta) only.
      The PS dependence of PDBu binding to Cys2(delta) was highly cooperative with Hill
      numbers lying in the range of 2.5-5.2. These results demonstrate the presence of
      striking functional differences between the cysteine-rich regions of nPKCdelta
      and the calcium-dependent isoform, cPKCgamma, where both cysteine-rich regions
      represent functional PDBu binding elements.

PMID- 9001404
TI  - Stabilization of cationic liposome-plasmid DNA complexes by polyamines and
      poly(ethylene glycol)-phospholipid conjugates for efficient in vivo gene
      delivery.
AB  - Stable complexes of cationic liposomes with plasmid DNA were prepared by (1)
      including a small amount of poly(ethylene glycol)-phospholipid conjugate or (2)
      condensing the DNA with polyamines prior to the formation of liposome-plasmid
      complexes. These preparations were stable for months at 4 degrees C and gave
      reproducible high transfection activity for in vivo gene delivery after
      intravenous injection in mice. Under these conditions, the expression of marker
      gene (luciferase) was primarily in the lungs (reaching values up to 3 ng
      expression per mg tissue protein), but also in other tissues to a lesser extent.
      Non-stabilized formulations lost all their transfection activity in 4 days. In
      these formulations cholesterol, not dioleoylphosphatidylethanolamine, was the
      helper lipid effective for sustaining high transfection activity in vivo. These
      new developments in formulation technology should enhance the potential for
      liposome-mediated gene therapy.

PMID- 9001405
TI  - Demonstration of dimer formation of the cytoplasmic domain of a transmembrane
      osmosensor protein, EnvZ, of Escherichia coli using Ni-histidine tag affinity
      chromatography.
AB  - EnvZ is a transmembrane osmosensor which regulates the phosphorylation of OmpR, a
      transcription factor for ompF and ompC genes which encode the major outer
      membrane porin proteins, OmpF and OmpC in Escherichia coli. Autophosphorylation
      of EnvZ occurs through a transphosphorylation reaction between two EnvZ
      molecules. To elucidate the molecular mechanism of signal transduction by EnvZ,
      we examined the dimer formation of the EnvZ cytoplasmic domain [EnvZ(C)]. For
      this purpose, we developed a method to determine the complex formation between
      the purified EnvZ(C) and the purified His6-EnvZ(C) by means of Ni-6xhistidine tag
      affinity chromatography. When the mixture of EnvZ(C) and His6-EnvZ(C) was applied
      to Ni-NTA resin, both His6-EnvZ(C) and EnvZ(C) were bound to the resin,
      indicating that EnvZ can form an oligomer without the periplasmic and
      transmembrane domains. Binding experiments using the Ni-NTA resin revealed that
      EnvZ(C) forms a dimer with the Ka value for dimerization being approximately
      10(5) M(-1) in the equilibrium state.

PMID- 9001406
TI  - Complementation of a yeast delta pkc1 mutant by the Arabidopsis proteinANT.
AB  - The Saccharomyces cerevisiae protein kinase C homologue, PKC1, is involved in
      maintenance of cell integrity during polarized growth. We have used a mutant
      complementation approach to investigate related signal transduction pathways in
      higher plants. Here we report the isolation of a cDNA from Arabidopsis thaliana
      which partially suppresses the lytic defect of a delta pkc1 yeast strain. The
      encoded protein, ANT, belongs to the AP2-related gene family and is essential for
      ovule development. Expression in yeast of a LexA-ANT fusion protein activates
      transcription of a reporter gene from promoters containing lexA operators. Our
      results support the idea that ANT acts as transcriptional activator in planta.

PMID- 9001407
TI  - Electron spin echo envelope modulation studies of the semiquinone anion radical
      of cholesterol oxidase from Brevibacterium sterolicum.
AB  - The electron spin echo envelope modulation (ESEEM) technique of pulsed EPR
      spectroscopy was applied to the anionic semiquinone of the cholesterol oxidase
      flavin cofactor, formed when the enzyme was photoreduced in the presence of 5
      deazariboflavin and EDTA. Fourier transforms of the three-pulse ESEEM spectra
      showed the presence of 14N nuclei magnetically coupled to the paramagnet. In 2H2O
      buffer the surroundings of the flavin ring were shown to be accessible to solvent
      exchange, with a deuterium population in close proximity to the paramagnetic
      centre. Upon binding of the pseudosubstrate, dehydroisoandrosterone, subtle
      changes were observed in the coupling to nitrogen nuclei, which are interpreted
      as changes in the electron density distribution of the flavin ring system. The
      results are discussed in terms of the three-dimensional structure reported for
      the protein and the flavin ring architecture.

PMID- 9001408
TI  - Characterization of the amsI gene product as a low molecular weight acid
      phosphatase controlling exopolysaccharide synthesis of Erwinia amylovora.
AB  - The ams region, responsible for amylovoran synthesis of the fireblight pathogen
      Erwinia amylovora, contains the gene amsI encoding a 144 amino acid protein with
      homology to mammalian low molecular weight acid phosphatases [Bugert and Geider
      (1995) Mol. Microbiol. 15, 917-9331. A DNA fragment with amsI was cloned under
      the control of the lac promoter on a high copy number plasmid. The gene product
      of amsl is about 17 kDa in a protein expression system and had the enzymatic
      activity of an acid phosphatase. This is the first report about a low molecular
      weight acid phosphatase activity in prokaryotes. As part of the large ams
      transcript, expression of amsI was affected by the activator proteins RcsA and
      RcsB. Overexpression of amsI in E. amylovora caused a strong increase of acid
      phosphatase activity, but additionally a strong reduction in EPS synthesis,
      phenotypically similar to a mutation in the gene. The gene product may
      participate in changes of phosphorylation required for the biosynthesis of EPS
      such as recycling the lipid carrier diphosphate to the monophosphate form.

PMID- 9001409
TI  - Continuous infusion of low-dose 5-Aza-2'-deoxycytidine in elderly patients with
      high-risk myelodysplastic syndrome.
AB  - There is no standard therapy for elderly patients with high-risk myelodysplastic
      syndrome (MDS). The treatment options of low-dose Ara-C and haematopoietic growth
      factors are disappointing in regard to response rate or response duration. We
      tested the treatment with a 72-h continuous infusion of low-dose 5-Aza-2'
      deoxycytidine (DAC) in a group of 29 elderly patients with high-risk MDS. In 15
      patients (54%) we observed a response. Eight complete responses were reached,
      even among patients with bad prognostic cytogenetic findings. The actuarial
      median survival from the start of the therapy was 46 weeks. The only (and major)
      toxicity was myelosuppression, leading to a prolonged cytopenic period and thus
      leading to five toxic deaths (17%) in this high-risk patient group. We conclude
      that DAC is an effective drug in the treatment of MDS patients and that it
      probably works via its cytotoxic activity. Myelotoxicity is its major adverse
      effect.

PMID- 9001410
TI  - The nuclear compartment of living cells is not an absolute immunologically
      sequestered site: evidence for spontaneous intranuclear entry of lupus
      autoantibodies to living cells.

PMID- 9001411
TI  - Tartrate-resistant acid phosphatase: gene structure and function.

PMID- 9001412
TI  - Howard Temin memorial lectureship. Molecular biology of HTLV-1: deregulation of
      host cell gene expression and cell cycle.

PMID- 9001413
TI  - Intensive chemotherapy with idarubicin, cytosine arabinoside, and granulocyte
      colony-stimulating factor (G-CSF) in patients with secondary and therapy-related
      acute myelogenous leukemia. Club de Reflexion en Hematologie.
AB  - Using a combination of intensive chemotherapy and G-CSF, we conducted a
      prospective trial designed to improve the complete remission (CR) rate in
      patients with AML evolving from a primary documented myelodysplastic syndrome
      (sAML) and therapy-related AML (tAML). Thirty-four patients (median age 61 years)
      with sAML (25 patients) or tAML (nine patients) entered the study. Induction
      course consisted of idarubicin (12 mg/m2 of body-surface area per day for 3 days)
      and intermediate-dose (ID) cytarabine in the 24 younger patients (1 g/m2 of body
      surface area as a 2 h infusion every 12 h for 5 days) or standard-dose (SD)
      cytarabine in the 10 older patients (100 mg/m2 of body-surface area per day as a
      continuous infusion for 7 days), followed by G-CSF until neutrophil recovery or
      treatment failure. Nineteen patients (56%, 13/24 in the ID group and 6/10 in the
      SD group) achieved a CR (14/25 sAML and 5/9 tAML). Early death occurred in four
      patients, but four additional patients died in CR from treatment-related toxicity
      (overall toxic death rate 24%). Initial cytogenetics was available in 33
      patients. The CR rate was significantly lower in patients with unfavorable
      cytogenetics compared to patients with intermediate cytogenetics (37% vs 79%).
      Median remission duration and overall survival were 3 and 9 months, respectively
      and not different between ID and SD patients. Although the treatment-related
      toxicity is high, a high CR rate can be obtained in these poor-risk AML patients
      with the use of intensive chemotherapy in combination with G-CSF, although the
      role of the latter is still to be proven. Results remain especially poor in
      patients with unfavorable cytogenetics. New approaches are needed to maintain
      remission in these high-risk AML patients.

PMID- 9001414
TI  - IL2 fused to lectin-deficient ricin is toxic to human leukemia cells expressing
      the IL2 receptor.
AB  - Interleukin-2 (IL2) fused to ricin B chain (RTB) with modifications of amino acid
      residues in each of three galactose-binding subdomains (1alpha, 1beta and 2gamma)
      was expressed in insect cells, purified by immunoaffinity chromatography and
      reassociated with ricin A chain (RTA). The fusion toxin-bound human leukemic
      cells with IL2 receptors and the binding was competed with IL2 but not
      asialofetuin. In contrast, binding was not observed with receptor negative human
      cell lines, and the fusion molecule very weakly bound asialofetuin (Kd= 10(-6)M),
      indicating lectin-deficient RTB. The IL2-lectin-deficient RTB-RTA intoxicated IL2
      receptor bearing cells as well as ricin or IL2-wild-type RTB-RTA. While ricin and
      IL2-wild-type RTB-RTA were equally toxic to receptor negative cell lines, the IL2
      lectin-deficient RTB-RTA was two-two and one half logs less cytotoxic to these
      cell lines. The sensitivity of receptor-positive cells to the lectin-deficient
      fusion protein suggests that high avidity intracellular galactose binding may not
      be required for ricin intoxication, at least in the case of IL2 receptor-targeted
      molecules. Furthermore, the potent selective cytotoxicity of the fusion protein
      suggests that the IL2-lectin-deficient RTB-RTA and similar ricin fusion molecules
      directed against other leukemic cell surface receptors provide a novel class of
      fusion toxins for therapy of human leukemias.

PMID- 9001415
TI  - Erythrocyte spermine levels: a prognostic parameter in childhood common acute
      lymphoblastic leukemia.
AB  - Polyamines have been implicated to play a role in cell proliferation and in
      cancer development. Ninety percent of the circulating spermidine (Spd) and
      spermine (Spm) are transported by red blood cells (RBC). RBC Spd and Spm levels
      were prospectively determined in 63 unselected children with common acute
      lymphoblastic leukemia. The Spm and Spd levels were not correlated with white
      blood cell (WBC) count. On the basis of the polyamine levels it was possible to
      discriminate four groups with P< 10(-3). In C1, C2, C3 and C4 group the Spm level
      was respectively 90 (39-597), 3.75 (1-7.45), 9.95 (2.9-12.6) and 17(6.3-33.8).
      The probability of relapse-free survival (RFS) of the 58 children who entered
      complete remission was 55% +/- 9. For the groups C1 (n = 6), C2 (n = 16), C3 (n =
      21) and C4 (n= 15) groups, the RFS was 25% +/- 20, 73% +/- 12, 73% +/- 13 and 32%
      +/- 13 respectively. For children with Spm levels <13/> or = 13nmol/8 x 10(9)
      RBC, event-free survival (EFS) was 54% +/- 11/33% +/- 10 and RFS was 64% +/-
      12/38% +/- 11 respectively (P < 0.03, P < 0.005). Our clinical study shows
      clearly that an RBC spermine level could be used as parameter of prognosis at the
      time of diagnosis, particularly for patients with intermediary WBC count.

PMID- 9001416
TI  - Long-term survival and development of secondary malignancies in patients with
      acute myeloid leukemia treated with aclarubicin or daunorubicin plus cytosine
      arabinoside followed by intensive consolidation chemotherapy in a Danish national
      phase III trial. Danish Society of Haematology Study Group on AML.
AB  - In 1991 we reported the results from a prospective randomised phase 3 trial
      comparing 7 days continuous infusion of cytosine arabinoside (ara-C) combined
      with either daunorubicin (DNR) or aclarubicin (ACR) as direct i.v. injection for
      3 days as induction chemotherapy (CT) for patients with de novo acute myeloid
      leukemia (AML) followed by early intensive consolidation CT with two alternating
      cycles of high-dose ara-C and two cycles of amsacrine plus etoposide, and finally
      3 days of daunomycin plus 7 days of ara-C as administered for induction of
      remission. A total of 174 patients with de novo AML in the age group 17-65 years
      were included. The patients have now been followed till death or for at least 7
      years, and an evaluation of the long-term survival and the risk of developing
      secondary neoplasms has been made. The overall survival rate 5-years after
      diagnosis was 23%, and after 10 years 19%. No difference was found between the
      two treatment regimens in overall survival or disease-free survival (DFS). For
      the subgroup of 99 patients who achieved complete remission after one or two
      induction courses, 5- and 10-year survival rates were 35% and 31% respectively,
      with the highest survival rates in the age group 17-39 years (57% at 5 years) as
      compared with 27% in patients aged 40-60 years (P= 0.007). Seven secondary
      neoplasms were diagnosed simultaneously with or after the diagnosis of AML
      indicating a standardized incidence ratio (SIR) of 3.41, (95% CI: 1.60-7.26). In
      three cases the secondary neoplasms were diagnosed simultaneously with the AML
      diagnosis and were for that reason completely unrelated to the chemotherapy
      administered for AML, as the psammomatous meningeoma diagnosed after only 8
      months. The remaining three neoplasms which developed subsequently did not
      significantly exceed the expected number, with a SIR = 1.46 (0.47-4.57). Thus, no
      increased risk of solid tumors causally related to the intensive chemotherapy for
      de novo AML was observed. However, a generally increased risk of solid tumors in
      patients diagnosed simultaneously with the AML diagnosis seems likely. Over 20%
      of the patients were alive and in complete remission 5 years after the AML
      diagnosis, and they have a high probability of surviving the next 5-year period.

PMID- 9001418
TI  - A novel energy dependent mechanism reducing daunorubicin accumulation in acute
      myeloid leukemia.
AB  - Using cyclosporin A (CsA) to inhibit P-glycoprotein (P-gp) function we showed
      previously that there was a discordance between the ability of acute myeloid
      leukemic (AML) blast cells to accumulate daunorubicin and P-gp antigen expression
      (Xie et al, Leukemia 1995; 9:1882-1887). This discordance suggests that a CsA
      sensitive drug efflux mechanism distinct from P-gp is expressed in many clinical
      samples. In the present study using the ATP depleting agents cyanide, azide, or
      dinitrophenol to inhibit energy dependent transport processes, we observed even
      larger increases in daunorubicin accumulation than were seen with CsA. Similar
      patterns were seen in a wide range of P-gp negative human cancer cell lines. Also
      the observed cyanide effect did not correlate with the expression of mRNA for
      multidrug resistance-associated protein (MRP), the only other member of the ABC
      family of membrane transporters that is known to be capable of effluxing
      daunorubicin. Thse results suggest that daunorubicin accumulation in many cases
      of AML is modulated by one or more novel energy-dependent processes that are
      distinct from P-gp or MRP. We speculate that this novel drug transport
      mechanism(s) may influence the response of AML patients to daunorubicin and other
      therapeutic agents.

PMID- 9001417
TI  - Response duration and recovery of CD4+ lymphocytes following deoxycoformycin in
      interferon-alpha-resistant hairy cell leukemia: 7-year follow-up.
AB  - The long-term outcome of patients with hairy cell leukemia resistant to
      interferon-alpha (IFN-alpha) following treatment with deoxycoformycin (DCF) was
      examined, and the kinetics of recovery of lymphocyte subsets and factors
      influencing the rate of recovery investigated. Between May 1986 and May 1989, 15
      patients with histologically confirmed hairy cell leukemia resistant to IFN-alpha
      received DCF 4 mg/m2 every 2 weeks with 12 cycles planned. All 15 patients were
      evaluable for response and have been followed for a median of 88 months (range,
      72 to 106 months) from the start of therapy. Fourteen patients responded to DCF,
      all attaining complete remission (CR) (response rate 93%; 95% confidence
      interval, 69% to 100%). Seven patients have developed recurrent disease after 45
      to 74 months. Using the method of Kaplan and Meier, the median remission duration
      is 74 months and, at 8 years, 46% (95% confidence interval, 33% to 59%) of
      patients are projected to be in ongoing CR. The seven relapsing patients have
      responded to treatment with 2-chlorodeoxyadenosine (2-CdA) and all 15 patients
      remain alive. After DCF, nadir CD4+ and CD8+ lymphocyte counts were significantly
      lower than prior to therapy (P < 0.0001 and P = 0.05, respectively), but returned
      to baseline levels during follow-up. Median times to attainment of the lower
      limit of the normal range of CD4+ and CD8+ lymphocytes were 54 and 36 months,
      respectively. Those patients who had previously undergone splenectomy (n=7) had
      higher baseline CD4+ (P= 0.073) and CD8+ (P= 0.043) lymphocyte counts and more
      rapid recovery of both CD4+ (P= 0.027) and CD8+ lymphocyte counts (P = 0.016)
      than non-splenectomized patients. One elderly patient (age, 78 years) was
      diagnosed with subsequent malignancy. No late opportunistic infections were
      observed. Resistance to IFN-alpha does not impair subsequent responsiveness of
      patients with hairy cell leukemia to treatment with DCF. Responses are durable
      and without evidence of long-term sequelae. CD4+ and CD8+ lymphocyte subsets
      recover slowly without clinical manifestations of immunodeficiency.
      Splenectomized patients appear to have higher baseline lymphocyte counts and more
      rapid lymphocyte recovery following treatment with DCF.

PMID- 9001419
TI  - Expression and regulation of G1 cell-cycle inhibitors (p16INK4A, p15INK4B,
      p18INK4C, p19INK4D) in human acute myeloid leukemia and normal myeloid cells.
AB  - In hematological malignancies, structural alterations of genes for G1-specific
      cyclin-dependent kinases inhibitors (CKIs) have been extensively investigated. G1
      CKIs might play an important role not only as tumor suppressor genes but also in
      cellular differentiation. We examined constitutive and differentiation-induced
      expression and regulation of the four members of the G1-CKI family p16INK4A,
      p15INK4B, p18INK4C and p19INK4D in acute myeloid leukemia as well as their
      expression in normal granulocytes and monocytes. p18INK4C and p19INK4D mRNA were
      expressed constitutively at high levels in seven myeloid cell lines and 16 AML
      patient samples, whereas expression of p15INK4B mRNA was very low and only
      detectable by nested RT-PCR analysis. During phorbol ester-induced monocytic
      differentiation of leukemic HL-60 cells expression of particular G1-CKIs was
      disparately regulated. This process was associated with growth arrest of the
      majority of the cells (> or = 80%) in G1/G0, and in parallel p15INK4B were
      upregulated whereas p18INK4C and p19INK4D expression was downregulated. In
      contrast, granulocytic differentiation induced by DMSO was accompanied by an
      increase of p18INK4C and p19INK4D expression only. PMA treatment of blast cells
      from two AML patients confirmed these cell line results. Disparate regulation of
      p15INK4B and p18INK4C mRNA was dependent on intermediary protein synthesis and
      occurred at the post-transcriptional level as shown by nuclear run-on analysis
      and mRNA half-life studies. In normal granulocytes and monocytes low constitutive
      p15INK4B and p18INK4C mRNA expression was detectable by RT-PCR only, but p19INK4D
      transcripts were noted by Northern blotting in both cell types. Disparate
      expression of G1-specific cell cycle inhibitors indicates complex and divergent
      roles of particular CKIs during normal and leukemic myeloid hematopoiesis.

PMID- 9001420
TI  - Potential role for concurrent abnormalities of the cyclin D1, p16CDKN2 and
      p15CDKN2B genes in certain B cell non-Hodgkin's lymphomas. Functional studies in
      a cell line (Granta 519).
AB  - Abnormalities of several cell-cycle regulatory genes including cyclin D1,
      p16CDKN2 and p15CDKN2B have been described in B cell non-Hodgkin's lymphoma (B
      NHL). We describe a new B-NHL cell line (Granta 519), with concurrent
      abnormalities of the cyclin D1, pl6CDKN2 and pl5CDKN2B genes. An independent
      clinical case of mantle cell NHL (Mc-NHL) with concomitant overexpression of
      cyclin D1, and deletion of the p16CDKN2 gene was also identified, suggesting that
      this combination of oncogenic aberration is a pathophysiologic contribution to a
      subset of NHL cases. More in-depth functional studies of this concept were
      facilitated by the availability of the cell line Granta 519 which was derived
      from a case of high-grade NHL and has a mature B cell immunophenotype.
      Cytogenetic analysis identified translocation t(11;14)(q13;q32) and complex
      rearrangements involving chromosomes 9p22, 13p21, 17pl1, and 18q21. Molecular
      analysis identified overexpression of cyclin D1 mRNA and biallelic deletion of
      the p16CDKN2 and p15CDKN2B genes. To elucidate the effect of these genetic
      abnormalities on the G1 control of Granta 519 cells, the level and function of
      the major components of the cyclinD/retinoblastoma (RB) pathway were
      investigated. Cyclin D1 was dominant among the D-type cyclins, formed abundant
      complexes with cyclin-dependent kinase (Cdk) Cdk4 rather than Cdk6, and the
      immunoprecipitated cyclin D1/Cdk4 holoenzyme was active as a pRB kinase.
      Electroporation of wild-type pl6CDKN2 arrested the Granta 519 cells in G1,
      consistent with the p16CDKN2 loss as a biologically relevant event during
      multistep evolution of the tumor, and with the expression of functional pRB.
      Direct cooperation of these distinct abnormalities to cell-cycle, deregulation in
      NHL cells was suggested by G1 acceleration upon inducible overexpression of
      cyclin D1 in a control breast cancer cell line lacking p16CDKN2, an effect which
      could be prevented by ectopic expression of p16CDKN2. Taken together, these data
      suggest that concurrent overexpression of cyclin D1 and functional elimination of
      p16CDKN2 and p15CDKN2B may characterize certain cases of mantle cell NHL, and
      that cooperation of the abnormalities is likely to provide a growth advantage of
      the tumour cells through more efficient inactivation of the RB tumor suppressor.
      Further clinicopathologic studies of this possibility are warranted.

PMID- 9001421
TI  - Cyclic AMP negatively controls c-myc transcription and G1 cell cycle progression
      in p210 BCR-ABL transformed cells: inhibitory activity exerted through cyclin D1
      and cdk4.
AB  - Raised intracellular cyclic AMP (cAMP) has been demonstrated to exert an
      antiproliferative effect in myeloid cells. How the antiproliferative activity of
      cAMP is exerted in p210 BCR-ABL transformed myeloid cells was the subject of this
      investigation. It was hypothesized that cyclin dependent kinase 4, cdk4, might be
      a critical target enzyme to affect the related events of c-myc transcription and
      progression through G1 phase of the cell cycle within cells transformed by p210
      BCR-ABL, and further, that cdk4 might be downregulated by cAMP to inhibit
      proliferation. In order to investigate the regulatory role of cdk4, synchronized
      cells were studied. In p210 BCR-ABL transformed cells transiting early G1 phase,
      treatment with a cAMP analogue led to inhibition of cyclin D1 synthesis, and
      marked reduction of cdk4 kinase activity. Within cells in which cdk4 was
      inhibited by cAMP, there was augmented interaction of E2F1 with the
      retinoblastoma protein, pRb in a nuclear matrix-associated cell fraction. As a
      result of E2F1 sequestration, raised intracellular cAMP was found to inhibit c
      myc transcription in p210 BCR-ABL transformed myeloid cells synchronously
      transiting the early G1 phase of the cell cycle. A target of this transcriptional
      suppression exerted by cAMP was the E2F site of the c-myc P2 promoter. On the
      other hand, cyclin D1 content was not reduced by cAMP in these cells when it was
      applied at a later cell cycle stage at the interface between G1 and S.
      Corresponding to lack of cyclin D1 inhibition in these later G1-to-S phase cells,
      cdk4 activity was only modestly suppressed, and c-myc mRNA expression was also
      inhibited to a lesser degree. These studies show that Rb interaction with E2F1 is
      regulated by cdk4 and cyclin D1 within p210 BCR-ABL transformed leukemia cells in
      early G1 phase of the cell cycle. In this context, both cyclin D1 and cdk4 are
      subject to the level of intracellular cAMP. This interaction between Rb and E2F1,
      which is subject to the level of cAMP, is critical to transcriptional control of
      c-myc. Further, pRb regulation of E2F activity affects cellular potential for G1
      S phase transition in p210 BCR-ABL transformed myeloid cells, in part, via its
      effect on c-myc transcription.

PMID- 9001423
TI  - Identification and functional analysis of multiple murine myeloperoxidase (MPO)
      promoters and comparison with the human MPO promoter region.
AB  - Myeloperoxidase (MPO) is an important component of the oxidative antibacterial
      defense system of granulocytes. Mammalian MPO gene expression has been most
      extensively studied in human and murine cells. Transcription of the human MPO
      gene appears to begin at a single initiation site and we have recently described
      the isolation and characterization of the corresponding human MPO promoter. On
      the other hand, MPO transcripts in murine myeloid cells show several distinct 5'
      termini, suggesting the existence of multiple murine MPO promoters. However,
      significant levels of endogenous murine MPO promoter activity have not been
      demonstrated heretofore, although several murine MPO enhancers have been
      described. We now report the identification and preliminary functional
      characterization of four distinct murine MPO promoters. Sequence comparison of
      the human and murine MPO promoter regions reveals homologues of three out of four
      of these murine promoters within the human MPO gene. However, only one of these
      sites appears to be functionally active in human myeloid cells, possibly because
      of the interposition of Alu sequences between the putative promoter sites in the
      human gene.

PMID- 9001422
TI  - Elf-2, a rhombotin-2 binding ets transcription factor: discovery and potential
      role in T cell leukemia.
AB  - Rhombotin-2 (RBTN-2) is a proto-oncogene only in the context of T lymphocytes. We
      postulated that the oncogenic effect of RBTN-2 in T cells is likely mediated by
      binding protein(s) with T cell-specific expression. By screening a T cell cDNA
      library, we identified a novel ets transcription factor that binds RBTN-2. This
      protein was named elf-2 because its DNA-binding domain is virtually identical to
      that of ets family member elf-1. Northern analyses showed similar levels of two
      elf-2 transcripts (3.5 kb and 3.8 kb) in all tissues except thymus. Thymocytes
      expressed four- to 10-fold greater amounts of the 3.5 kb transcript than other
      tissues. Sequence analyses of cDNA clones indicated that these transcripts encode
      proteins differing only at their amino termini, and likely represent
      alternatively spliced isoforms. These isoforms (elf-2a and elf-2b) contain
      identical RBTN-2 binding regions and DNA-binding domains. Elf-2b lacks a putative
      transactivation domain. The expression patterns suggest that RBTN-2 normally
      interacts equally with elf-2a and elf-2b. In contrast, when RBTN-2 is
      inappropriately expressed in T cells, RBTN-2 would interact predominantly with
      elf-2b; this interaction may lead to T cell proliferation.

PMID- 9001424
TI  - TCR gamma delta+ cells expressing Vgamma 9V delta2, which normally predominate
      the blood, are found in the spleens of patients with hairy cell leukemia.
AB  - T cell receptor gamma delta+ (TCR gamma delta+) cells are present in all lymphoid
      tissues, but at lower frequencies than TCR alpha beta+ cells. In normal spleens,
      they account for about 15-20% of CD3+ cells. In hairy cell leukemia (HCL), a B
      cell malignancy with a characteristic involvement of the spleen, splenic T cells
      of approximately 40% of the examined patients showed a remarkable increase in
      CD3+ TCR gamma delta+ cells. Therefore, we studied the TCR gamma delta phenotypes
      in blood and spleen of 12 HCL patients in comparison with normal samples. In
      normal blood (n= 6) the majority of TCR gamma delta+ cells expressed the Vgamma
      9V delta2 phenotype, while in normal spleens (n = 9) a different population was
      found expressing Vdelta1. In contrast, six of eight paired blood and spleen
      samples of individual HCL patients demonstrated the same phenotype with
      predominantly Vgamma 9V delta2 expression. This change in splenic TCR gamma delta
      usage in patients with HCL might be the result of cell-trapping, or an
      infiltration of TCR gamma delta+ cells from the blood.

PMID- 9001425
TI  - Mutation analysis of the WT1 gene in sporadic childhood leukaemia.
AB  - The 10 coding exons of the WT1 gene, from 39 bp upstream of the translation
      initiation codon to 12 bp downstream of the stop codon, were examined for point
      mutations in a panel of 48 sporadic childhood acute leukaemias using the single
      stranded conformational polymorphism (SSCP) assay. The panel included 33 cases of
      acute lymphocytic leukaemia and 15 cases of acute myeloid leukaemia. This is the
      first study in which sporadic childhood leukaemias have been examined for WT1
      point mutations across the entire coding region of the WT1 gene, however, no
      tumorigenic point mutations or small deletions or insertions could be identified
      in these patients. A previously described polymorphism in exon 7, resulting in an
      A to G transition in an arginine codon, was observed at a frequency of 21.5%,
      equivalent to that seen in the normal population. This study suggests that point
      mutations in the coding regions of the WT1 occur infrequently in leukaemias of
      childhood.

PMID- 9001426
TI  - Radiation-enhanced expression of interferon-inducible genes in the KG1a primitive
      hematopoietic cell line.
AB  - X-ray treatment induces a complex molecular response in hematopoietic cells
      leading to cell death. Using the mRNA differential display technique, we searched
      for genes whose expression was modified by ionizing radiation (IR) in the human
      p53-deficient leukemic cell line KG1a. We isolated a partial cDNA corresponding
      to the interferon (IFN)-inducible 1-8d gene. The expression of both 1-8d and 9
      27, another gene from the same IFN-inducible family, was increased 24 and 48 h
      following irradiation. We did not find enhancement of either IFNgamma mRNA or
      interferon regulatory factor-1 (IRF-1) mRNA in irradiated KG1a cells, indicating
      that 1-8d and 9-27 enhancement was not due to an IFN activation. Thus, the
      induction of IFN-inducible genes by IR may provide a link between radiation
      induced and IFN-mediated cell death.

PMID- 9001427
TI  - Mutations in the granulocyte colony-stimulating factor receptor gene in patients
      with severe congenital neutropenia.
AB  - Previously, nonsense mutations in the gene encoding the granulocyte colony
      stimulating factor receptor (G-CSF-R) have been described in three patients with
      severe congenital neutropenia (SCN) (Proc Natl Acad Sci USA 1994; 91: 4480; New
      Engl J Med 1995; 333: 487). The mutations resulted in the truncation of the
      carboxy-terminal region of G-CSF-R essential for transduction of maturation
      signals. Two of these patients developed acute myeloblastic leukemia (AML). We
      present the results of a search among 20 additional cases of congenital
      neutropenia (CN) and SCN for the presence of mutations in the cytoplasmic domain
      of G-CSF-R. This series includes patients with familial and nonfamilial forms of
      CN and SCN. Mutations in the G-CSF-R gene were found in two new SCN cases. These
      mutations were nonsense mutations, located in the same cytoplasmic region of G
      CSF-R as those found earlier, resulting in the truncation of the C-terminus. Both
      of these patients developed AML. None of the other patients showed clinical
      symptoms or cytogenetic features indicative of AML or progression to leukemia.
      The analysis in this extended series of patients thus has revealed five SCN cases
      with G-CSF-R mutations, four of whom developed AML. These results add support to
      the notion that mutations in the G-CSF-R gene, affecting the maturation signaling
      function of the receptor, define a distinct subgroup of SCN with increased
      susceptibilty to AML.

PMID- 9001428
TI  - Efficient long-term maintenance of chronic myeloid leukemic cobblestone area
      forming cells on a murine stromal cell line.
AB  - Stroma-supported long-term cultures (LTC) of chronic myeloid leukemia (CML)
      progenitor cells have previously revealed differences between normal and
      malignant stem cells with respect to their maintenance and adhesive properties.
      Using the cobblestone area forming cell (CAFC) assay and LTC, we have examined
      the frequencies of stem cell subsets, their ability for long-term progenitor cell
      production and the relative frequencies of malignant and normal progenitor cells
      before and after a 5-6 week culture period. Cells were obtained from bone marrow
      (BM) and peripheral blood (PB) samples of patients in chronic phase CML. CD34
      enriched cells were sorted by FACS on the basis of CD34 and CD38 expression and
      overlaid on confluent stromal layers of murine FBMD-1 cells. The presence of the
      bcr/abl chimeric gene was detected by fluorescent in situ hybridization (FISH)
      using differently labelled bcr and abl-specific probes. In the CD34pos/CD38pos
      subset of CML-PB, representing 64-95% of CD34pos cells, CAFC frequencies at week
      1 (wk-1) were much higher than those of CAFC wk-5 (1.10(4)/10(5) cells vs
      1.10(3)/10(5)). In contrast, in the CD34pos/CD38neg subset, representing 2-3% of
      CD34pos cells, the frequency of CAFC wk-1 was only 1.10(2)/10(5) cells, but a
      high CAFC frequency (10(3)-10(4)/10(5)) was detected after 5 weeks of culture.
      CAFC frequencies in the CD34pos subset obtained from CML-BM were 10- to 100-fold
      lower than those from CML-PB, but displayed a similar distribution over CD38pos,
      CD38dim and CD38neg cells. Analysis of the percentage of Philadelphia chromosome
      positive (Ph+) and Ph- cells by FISH on freshly sorted cells revealed that normal
      cells were not enriched in any CD34pos/CD38 subset. In addition, Ph- as well as
      Ph+ cells were maintained with similar efficiency throughout 5 week LTC. These
      results demonstrate that immature normal and malignant stem cells in CML have a
      comparable distribution on the basis of CD34 and CD38 expression. The ability to
      maintain immature normal and malignant hemopoietic cells with similar efficiency
      in LTC provides a model enabling a direct comparison of differential effects of
      cytokines or drugs on either normal or malignant immature stem cells in CML.

PMID- 9001430
TI  - Stroma-conditioned media improve expansion of human primitive hematopoietic stem
      cells and progenitor cells.
AB  - It has been reported that stroma-dependent cultures support proliferation of
      hematopoietic stem cells (HSC). In order to investigate the effect of soluble
      stromal factors, we developed short-term serum-low liquid cultures in which the
      effect of stroma-conditioned media (SCM) from the murine FBMD-1, and human L87/4
      and L88/5 cell lines was studied on the maintenance and expansion of various
      human HSC subsets in CD34-positive selected mobilized peripheral blood stem cells
      (PBSC) from autologous transplants of lymphoma and multiple myeloma patients. The
      human cobblestone area forming cell (CAFC) assay was employed to determine the
      frequencies of both the CAFC weeks 2 to 4 as tentative indicators of progenitor
      and transiently repopulating HSC, and the more primitive CAFC weeks 6 to 8 as
      indicators of long-term repopulating HSC. In 7-day liquid cultures containing
      interleukin-3 (IL-3), stem cell factor (SCF) and IL-6, we recovered 3.0-fold more
      colony-forming cells (CFC) and 1.7- to 1.9-fold more CAFC weeks 2 and 4. The
      absolute number of primitive CAFC weeks 6 and 8 were only maintained (1.1- to 1.4
      fold) in these liquid cultures. This modest expansion was significantly improved
      by the addition of SCM from the FBMD-1, L87/4 or L88/5 cell lines. Output CFC
      numbers were 6.8-, 5.8- and 9.9-fold higher, respectively, than the input values,
      while absolute CAFC week 2 to 4 numbers were 4.5-, 10.2- and 10.2-fold expanded,
      respectively. The addition of SCM also improved expansion of the more primitive
      CAFC week 6 to 8 stem cell subsets by 2.2-, 4.5- and 4.9-fold, respectively. The
      addition of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage
      CSF (GM-CSF), IL-1beta, IL-11 or macrophage inflammatory protein-1alpha to
      cultures containing IL-3, SCF and IL-6 could not explain the SCM effect and in
      all these combinations SCM addition further increased the recovery of HSC
      subsets. Similarly, addition of anti-cytokine antibodies (ie alpha-G-CSF, alpha
      GM-CSF, alpha-IL-11, alpha-leukemia inhibitory factor) to liquid cultures
      containing IL-3, SCF, IL-6 and SCM could not neutralize the SCM effect. These
      data indicate that SCM significantly enhances expansion of primitive HSC and
      progenitor cells from CD34-selected PBSC in 7-day cultures and in synergistic
      combination with multiple cytokines at optimal concentrations. As a result, SCM
      is a useful component of short-term liquid culture procedures for clinical
      expansion or manipulation of primitive HSC.

PMID- 9001429
TI  - Increased serum levels of soluble CD44 standard, but not of variant isoforms v5
      and v6, in B cell chronic lymphocytic leukemia.
AB  - The CD44 cell surface proteoglycan participates in a variety of functions
      including lymphohematopoiesis, lymphocyte homing and tumor metastasis. In
      addition to the standard form (CD44st), a large family of variant isoforms
      (CD44v) is generated by alternative splicing of a single gene. Certain CD44v (v5
      and V6) are upregulated in the course of neoplastic progression and reflect the
      metastatic potential of tumor cells. CD44 v6 is expressed in high-grade non
      Hodgkin's lymphoma cells and is released in the serum, thus providing a soluble
      marker that reflects tumor burden, disease progression and treatment response.
      Here we show that serum CD44st is elevated in approximately half of B-CLL
      patients. In contrast, CD44v5 and v6 are detected at normal levels in the large
      majority of the cases. CD44st serum levels correlate significantly with the
      number of circulating leukemic B cells and with the levels of another soluble B
      CLL marker, beta2-microglobulin. Immunoprecipitation analyses of B-CLL sera allow
      detection of several high molecular weight bands and of a 78 kDa band that
      represents a soluble form of CD44st and is 4 kDa lower than a similar band (82
      kDa) detected in B-CLL cell lysates. Elevated serum CD44st associates with a
      number of unfavorable prognostic factors such as high peripheral blood
      lymphocytosis, splenomegaly, advanced disease stage and therapy requirement. A
      follow-up study indicates that serum levels of CD44st are related to disease
      status, thus reinforcing our veiw that this molecule may represent a reliable
      tumor marker in B-CLL.

PMID- 9001431
TI  - Absence of microsatellite instability during the progression of chronic
      myelocytic leukemia.
AB  - Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed
      throughout the genome. To test the occurrence of genetic instability in the
      progression of chronic myelocytic leukemia (CML), we studied microsatellite
      instability (MSI) in 17 patients with CML. The DNAs from both chronic phase and
      blast crisis were analyzed at 10 loci. No MSI was observed in any of the 17 cases
      of blast crisis. These results indicate that MSI is rare and is not associated
      with progression to blast crisis in most cases of CML.

PMID- 9001432
TI  - The use of monoclonal gene rearrangement for detection of minimal residual
      disease in acute lymphoblastic leukemia of childhood.
AB  - Sensitive quantification of minimal residual disease (MRD) using the polymerase
      chain reaction (PCR) is strongly predictive of outcome in childhood acute
      lymphoblastic leukemia (ALL), with MRD levels at the end of induction therapy of
      >10(-3) predicting a poor outcome. Methods for sensitive quantification are,
      however, complicated and time-consuming. Detection by PCR of monoclonal
      immunoglobulin heavy chain (IgH) and T cell receptor (TCR) gene rearrangements is
      simple and can be used in routine laboratories but is non-quantitative and of
      lower but uncertain sensitivity. The aim of this study was to determine the value
      of detection of monoclonality in identification of different levels of MRD. We
      looked for monoclonality in 64 bone marrow aspirates which had been obtained from
      31 patients with B lineage ALL at various times during induction therapy and for
      which levels of MRD had been determined by limiting dilution analysis using
      patient-specific PCR primers. Detection of monoclonality identified levels of MRD
      of > or =10(-3) during induction with a sensitivity of 78% and a specificity of
      93%. The positive and negative predictive values were 0.86 and 0.88,
      respectively. The sensitivity of detection of a monoclonal IgH rearrangement was
      greater than that for the TCRgamma locus during induction as an IgH rearrangement
      was detected more often than a TCRgamma rearrangement in patients who had both
      IgH and TCRgamma rearrangement at diagnosis. Detection of monoclonality is
      therefore a simple and quick test applicable to the majority of patients with ALL
      and it may be useful in identifying high-risk patients at the end of induction
      and in identifying relapsing patients later during therapy.

PMID- 9001433
TI  - The 30/35 kDa chymotryptic fragment of fibronectin enhances retroviral-mediated
      gene transfer in purified chronic myelogenous leukemia bone marrow progenitors.
AB  - We have previously shown by reverse transcriptase-PCR (rtPCR) that CML CD34+ HLA
      DR- cells are enriched for BCR/ABL(-) hematopoietic progenitor cells (HPC) while
      leukemic HPC reside predominately within CML CD34+ HLA-DR+ cells. We investigated
      whether the 30/35 kDa fragment of fibronectin (FN) could be used to enhance
      retroviral-mediated gene transfer (RMGT) in chronic phase CML marrow HPC. CML
      CD34+ HLA-DR- and CD34+ HLA-DR+ cells were transduced with vector supernate
      containing the neomycin resistance gene on plates coated with either FN or bovine
      serum albumin (BSA) as control, then assayed for transduced HPC in progenitor
      cell assays in the presence or absence of G418. Transduction efficiency of CML
      CD34+ HLA-DR- cells over BSA ranged from 0.09 to 7.2% (mean 3.3 +/- 1.5%), while
      that over FN plates ranged from 3.8 to 23% (mean 11.0 +/- 4.5%) (n = 4).
      Transduction efficiencies of CML CD34+ HLA-DR+ cells ranged from 0.4 to 9.8%
      (mean 3.7 +/- 1.7%) and 6.0 to 26% (mean 17.3 +/- 4.5%) (n = 5) over BSA and FN,
      respectively. rtPCR analysis for BCR/ABL mRNA of individual G418-resistant HPC
      generated from CD34+ HLA-DR- cells revealed that normal BCR/ABL(-) HPC were
      successfully transduced under these experimental conditions. These results
      demonstrate the feasibility of transducing normal CML primitive HPC, and
      illustrate the potential clinical use of FN in the setting of gene therapy for
      CML, as well as other diseases.

PMID- 9001435
TI  - Myelodysplasia following treatment of chronic lymphocytic leukemia (CLL) with 2
      chlorodeoxyadenosine (2-CdA)

PMID- 9001434
TI  - Myelodysplastic syndrome following successful therapy of acute promyelocytic
      leukemia.
AB  - We describe a patient with acute promyelocytic leukemia (APL) who was
      successfully induced into remission with all-trans retinoic acid (ATRA) and
      idarubicin, but developed myelodysplastic syndrome (MDS) with monosomy 7 shortly
      after conclusion of maintenance therapy with idarubicin alternating with 6
      mercaptopurine, vincristine, methotrexate and prednisone. Patients on combination
      regimens of ATRA or other retinoids and chemotherapy, which are being
      increasingly used in recent years, should be closely monitored for the
      development of potentially new complications including MDS.

PMID- 9001436
TI  - Pure red cell aplasia caused by B19 parvovirus infection after autologous blood
      stem cell transplantation in a patient with chronic lymphocytic leukemia.

PMID- 9001437
TI  - Translocation (3;21)(q26;q22) in de novo acute myelogenous leukemia.

PMID- 9001438
TI  - Neuropeptide Y receptor subtypes.
AB  - Neuropeptide Y (NPY) is an amidated 36-amino acid peptide with a wide
      distribution in the central and peripheral nervous system. It can evoke numerous
      physiological responses by activating specific receptors. Studies using NPY
      analogs in various model systems and cell types demonstrate different orders of
      ligand potency and receptor binding affinity. These studies suggest the existence
      of multiple subtypes of NPY receptors. NPY has been described to bind to at least
      three different receptors, Y1, Y2 and Y3. NPY has also been shown to interact
      with sigma receptor in vivo and in vitro. There are indications that more
      subtypes might exist. Ligand binding studies reveal that Y1, Y2 and Y3 receptors
      are all G-protein coupled. It is not yet confirmed whether the sigma receptor
      that interacts with NPY is G-protein coupled. Some studies show that NPY
      receptors may interact with other classical receptors, including alpha- and beta
      adrenoceptors and cholinergic receptors. In the case of alpha- and beta
      adrenoceptors, the receptor-receptor interaction is possibly via a pertussis
      toxin-sensitive G-protein. NPY receptors are coupled to various signal
      transduction mechanisms including inhibition of adenylate cyclase, and
      stimulation or inhibition of increases in intracellular Ca2+. Specific links
      between individual NPY receptor subtype and a particular signal transduction
      pathway are not established.

PMID- 9001439
TI  - Aging and acute stress decrease corticotropin releasing hormone in the ovary of
      the Fischer 344/N rat.
AB  - Corticotropin-releasing hormone (CRH), originally isolated from the hypothalamus,
      is widely distributed in many extrahypothalamic central nervous system sites, and
      in the periphery. Immunoreactive (ir)-CRH has been identified in rat and human
      inflammatory sites, in rat testicular Leydig cells, and in rat thecal and stromal
      ovarian cells. In the current study, we investigated whether aging and stress are
      associated with changes in ovarian ir-CRH in the rat. Healthy young (3-4 mo) and
      old (24 mo) female Fischer 344/N rats (6 per group) were studied in the morning,
      before and after being stressed by 120 min of immobilization, and were sacrificed
      by decapitation. Young females were all in proestrous, and old females were in
      constant anestrous. Pre-immobilization corticosterone (CORT) levels were similar
      in both age groups; immobilization produced a dramatic increase in CORT in both
      groups; however, the increase was smaller in the old rats, although this did not
      reach statistical significance (P < 0.06). Immunoreactive CRH was detected in the
      ovaries of all rats, and its distribution and intensity were quantified masked to
      the age and treatment group, in the theca, granulosa, stroma, and corpus luteum.
      At baseline, ir-CRH was 50% lower in old than in young rats in the theca and
      stroma by both distribution and intensity. Stress was associated with a decrease
      of ir-CRH levels in the theca in both age groups, albeit to a significantly
      lesser extent in old rats (old 35% versus young 70%). These data suggest a
      functional and, perhaps, developmental role for ovarian CRH.

PMID- 9001441
TI  - Paracrine function of endothelium-derived nitric oxide.
AB  - We explored whether endothelium-derived nitric oxide (EDNO) acts in an autocrine
      or paracrine fashion to activate the soluble guanylate cyclase by measuring the
      elevations of cGMP levels. Comparisons were made between two culture models in
      which EDNO can stimulate cGMP synthesis within the same cells (endothelial cells)
      where it is formed, or in the neighboring cells (smooth muscle cells). The basal
      amount of EDNO showed no difference in cGMP levels when the endothelial cells
      (EC) were cultured either alone (iso-culture) or together with the smooth muscle
      cells (SMC, co-culture). However, cGMP levels were synergistically increased by
      the BK-stimulated EDNO when EC were co-cultured with SMC. The synergistical
      increase was significantly inhibited by 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI
      186), an extracellular radical scavenger. These findings suggest that the tonic
      formed basal EDNO has an autocrine effect on cGMP levels of EC themselves. In
      contrast, BK-stimulated phasic formed EDNO has not only an autocrine effect, but
      also a paracrine effect on cGMP levels of EC themselves and the adjacent SMC.

PMID- 9001440
TI  - The renin angiotensin system and nociception in spontaneously hypertensive rats.
AB  - This study investigated the effects of captopril, hydralazine and losartan on the
      locomotor activity, tailflick and hot plate latencies in spontaneously
      hypertensive rats (SHR) and their genetic controls the Wistar-Kyoto rat (WKY).
      The increased hot plate latencies normally exhibited by the spontaneously
      hypertensive rat were reduced or abolished by captopril (95 mg/kg/day p.o.) and
      losartan (18 mg/kg/day p.o.) treatment, but were unaffected by hydralazine (19
      mg/kg/day p.o.). There were no observable effects of any of the drugs on
      tailflick latencies or locomotor activity. The results highlight a potential role
      for angiotensin II in analgesia that is independent of blood pressure change.

PMID- 9001442
TI  - Biochemical alterations in guinea pig adrenal cortex following administration of
      PD 132301-2, an inhibitor of acyl-CoA:cholesterol acyltransferase.
AB  - To assess whether previously reported ultrastructural alterations of
      adrenocortical mitochondria induced by the acyl-CoA:cholesterol acyltransferase
      (ACAT) inhibitor PD 132301-2 are accompanied by functional deficits in tissue
      energy stores, phosphorylated adenine nucleotide levels in guinea pig adrenal
      cortex were quantitated. Adrenals of male guinea pigs were obtained at 1, 2, 6,
      or 24 hours after oral administration of 100 mg/kg PD 132301-2 or 0.5%
      methylcellulose vehicle. In treated animals, ATP levels and ATP/ADP ratios were
      decreased approximately 50% with concurrent increases in AMP. Calculated energy
      charge was also decreased; these decreases were maximal by 6 hours. Cholesterol
      esterification in adrenal cortex was inhibited, resulting in progressive
      accumulation of free cholesterol up to 3-fold over control by 24 hours,
      consistent with the ACAT inhibitory activity of the drug. These data suggest that
      PD 132301-2 distributes to the adrenal cortex where early alterations of tissue
      bioenergetics occur in a time frame consistent with ultrastructural alterations
      of mitochondria.

PMID- 9001443
TI  - Osteopenia in genetically diabetic DB/DB mice and effects of 1alpha
      hydroxyvitamin D3 on the osteopenia. Basic Research Group.
AB  - To explore the pathogenesis of non-insulin-dependent diabetes mellitus associated
      osteopenia, we examined age-related changes of the femur metaphyseal bone mineral
      density in genetically diabetic (db/db) mice and non-diabetic (+/+) mice of the
      same strain using single photon absorptiometry and characterized the osteopenia
      pharmacologically and biochemically. Bone mineral density increased with age in
      the +/+ mice from 5 to 16 weeks of age, but reached a plateau in the db/db mice
      at 8 weeks of age, and significant differences between the two groups were
      observed after 12 weeks of age. Ash weight (A) and dry weight (D) of the femur
      and A/D ratio were significant lower in the db/db mice than in the +/+ mice after
      8 weeks of age. Significant elevations of serum calcium and parathyroid hormone
      (PTH) were observed after 8 weeks and 12 weeks of age, respectively. Serum
      1alpha,25-dihydroxyvitamin D levels were significantly decreased in the db/db
      mice compared to the +/+ mice. Daily oral treatment with 1alpha-hydroxyvitamin D3
      (1alpha-(OH)D3) for 4 weeks starting from 8 weeks of age significantly attenuated
      the bone loss in the db/db mice. These results suggest that an impaired bone
      mineralization probably by insufficient vitamin D activity and high PTH levels
      are involved in the osteopenia in the db/db mice. 1alpha-(OH)D3 exerted
      beneficial effects on the bone loss.

PMID- 9001444
TI  - Effects of pulsatile pituitary adenylate cyclase activating polypeptide (PACAP)
      on gonadotropin secretion and subunit mRNA levels in perifused rat pituitary
      cells.
AB  - The effects of pituitary adenylate cyclase activating polypeptide (PACAP)
      administered intermittently on gonadotropin secretion and subunit mRNA levels in
      anterior pituitary cells from 7wk old intact and orchidectomized rats were
      studied. Cells were perifused for 9 h with hourly pulses of 2.5 nM GnRH or 10 nM
      PACAP, or with medium alone. Pulsatile PACAP initiated episodes of LH, FSH and
      alpha-subunit secretion, but was much less effective than GnRH. Responsiveness
      declined with repeated pulses of PACAP, although interpulse secretion increased
      gradually throughout the experiment. PACAP was a slightly more effective
      stimulator of LH release by pituitary cells from castrated than intact rats. At
      the completion of perifusion, pituitary RNA from castrated rats was extracted for
      measurement of gonadotropin subunit mRNA levels. Pulsatile PACAP stimulated alpha
      subunit and LHbeta mRNA levels but did not affect FSHbeta mRNA. By contrast,
      continuous PACAP increased alpha-subunit mRNA levels, but suppressed FSHbeta mRNA
      without affecting LHbeta mRNA. We conclude that pulsatile PACAP is a relatively
      ineffective stimulator of gonadotropin secretion when administered alone, and
      regulates gonadotopin subunit gene expression quite differently than continuous
      PACAP. We propose that the mode of PACAP secretion in vivo may be a determinant
      of the differential expression of the gonadotropin subunit genes.

PMID- 9001446
TI  - CYP2E1 genotypes and serum LAP in Japanese alcoholics.
AB  - The genotypes of the ALDH2 and CYP2E1 loci of Japanese alcoholic patients were
      determined to investigate the susceptibility to alcoholic liver injury. In
      alcoholics with a liver-function disorder, a significant association was observed
      between the genotypes of the CYP2E1 loci and the serum level of a liver-derived
      enzyme, LAP. However, there was no significant association between the ALDH2
      genotypes and liver dysfunction.

PMID- 9001445
TI  - Combined response of plasma and platelet catecholamines to different types of
      short-term stress.
AB  - Platelet catecholamines (CAs) do not seem to reflect the acute increases in
      plasma CAs observed during stress, at least over short periods of time. However,
      it is well known that stress, via the release of plasma CAs, is capable of
      affecting platelet function. To better address this issue, we studied platelet
      and plasma levels of free noradrenaline (NA), adrenaline (A), and dopamine (DA)
      in 10 healthy subjects undergoing three different stress tests: insulin tolerance
      test (ITT), cold pressor test (CPT) and handgrip test (HT). We also evaluated
      platelet count and platelet mean volume (MPV). ITT caused a considerable increase
      in plasma NA and a massive release of plasma A, while CPT and HT induced discrete
      increases only in plasma NA. ITT induced a significant decrease in platelet DA
      and a trend toward a decrease in platelet NA, along with a significant increase
      in MPV. All these changes occurred in coincidence with the peak levels of plasma
      CAs. No changes in platelet variables were observed in response to both CPT and
      HT. The modifications observed during ITT are likely to represent signs of an
      initial platelet activation in response to the acute plasma CA elevations this
      test was able to elicit. Our data show that platelet CA content does not
      represent a mere reflection of the circulating concentrations of plasma CAs, but
      it is the result of a dynamic balance between these two compartments.

PMID- 9001447
TI  - The effect of alpha 1-blocking vasodilator on fetal growth and uteroplacental
      blood flow in streptozotocin-induced diabetic rats.
AB  - For largely unknown reasons, severe diabetes mellitus in pregnant rats results in
      fetal growth retardation. In order to clarify the mechanism of this phenomenon,
      the relationship between the fetal growth and the uteroplacental blood flow, and
      the fetal serum insulin and IGF-1 concentrations were studied in streptozotocine
      induced diabetic and control pregnant rats. As compared to control rats, diabetic
      rats had significantly reduced uteroplacental blood flow, and the mean body
      weight of the fetuses was significantly lower. Treatment of diabetic rats with an
      alpha1-blocking vasodilator, urapidil, restored uteroplacental blood flow and
      fetal body weight without affecting hyperglycemia. There was no significant
      difference between diabetic and normal rats with respect to insulin and IGF-1
      concentrations in fetal plasma, although the mean value was slightly lower in the
      diabetic. We conclude that reduced uteroplacental blood flow is a major factor in
      the establishment of fetal growth retardation in diabetic pregnancies.

PMID- 9001448
TI  - Ischemia increases tissue and decreases extracellular levels of acid dopamine
      metabolites in the rat striatum: further evidence for active transport of
      metabolites.
AB  - During 30 minutes of global forebrain ischemia in rats, striatal intracellular
      levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increase
      at the same time extracellular levels, measured by microdialysis, decrease. If
      DOPAC and HVA were free to diffuse out of cells, these changes in opposite
      directions should not occur. These data support the theory that a membrane
      potential-dependent active transport system is required for DOPAC and HVA to
      leave striatal cells. During ischemia and subsequent to ATP depletion, neurons
      and glia depolarize and active transport systems fail. DOPAC and HVA, which are
      still being produced inside neurons and possibly glia, can not be transported out
      of these cells and accumulate intracellularly.

PMID- 9001449
TI  - Genetic control of biological rhythms: independent expression of each rhythm
      parameter.
AB  - Biological rhythm whose pattern approaches a sinusoidal curve can be
      characterized by four parameters: Period, Mesor, Acrophase and Amplitude.
      Inheritance patterns of these parameters were assessed by monitoring White Blood
      Cell (WBC) count rhythms of C57BL/6J mice, BALB/c mice and the F1 progeny prior
      and after injection of Cisplatinum at either 0900, 1500, 2100, or 0300. All
      untreated mice exhibited similar WBC rhythms while a variety of rhythm phenotypes
      was revealed among the injected mice. Analyses of the variety in the parental
      strains and F1 progeny suggested that each of the rhythm parameters is
      independently controlled.

PMID- 9001450
TI  - Functional role of nitric oxide in guinea pig tracheal epithelium.
AB  - Nitric oxide (NO) may play an important regulatory role in airway function. We
      have, thus, investigated in vitro whether epithelium derived NO may modulate
      cholinergic neurotransmission, via release of NO in guinea pig trachea, by using
      L-arginine (L-ARG), a precursor of NO synthesis, and L-N(G)-nitro-arginine-methyl
      ester (L-NAME), an inhibitor of NO synthase. Results show that L-ARG and L-NAME
      modify acetylcholine sensitivity in epithelium-intact smooth muscle preparations,
      suggesting a probable NO synthesis by tracheal guinea pig epithelium.

PMID- 9001451
TI  - New technologies propel nursing profession forward: nursing informatics offers
      limitless opportunities.

PMID- 9001452
TI  - Telehealth: nursing grapples with increasing care access without endangering
      quality.

PMID- 9001453
TI  - Health care in the 21st century.

PMID- 9001454
TI  - The evolution of managed care: new jobs for nurses in the 21st century. As I see
      it.

PMID- 9001455
TI  - ANA quality initiative reaches out to states.

PMID- 9001456
TI  - Nursing takes leading role in genetics education: coalition formed to increase
      provider awareness on genetics technologies.

PMID- 9001457
TI  - Mid-1900s: ANA unites profession, leads nursing into era of collective
      bargaining.

PMID- 9001459
TI  - ANA succeeds in getting Community Nursing Organization project extended one year.

PMID- 9001458
TI  - ANA pushes Congress to eliminate gag rules.

PMID- 9001460
TI  - Recalling the long road to collective bargaining.

PMID- 9001461
TI  - Nurses use entrepreneurship to meet patient needs, personal goals.

PMID- 9001462
TI  - Does the world need the BMJ?

PMID- 9001463
TI  - Hangovers.

PMID- 9001464
TI  - Monitoring blood glucose in gestational diabetes.

PMID- 9001465
TI  - Controlling chickenpox in hospitals.

PMID- 9001466
TI  - Polymerase chain reaction.

PMID- 9001467
TI  - Court to examine legality of compulsory caesarean sections.

PMID- 9001468
TI  - Gag clauses ruled illegal in United States.

PMID- 9001469
TI  - Gap between death rates of rich and poor widens.

PMID- 9001471
TI  - The scourge of the tobacco industry steps down.

PMID- 9001470
TI  - People who cause accidents should pay for victims' care.

PMID- 9001472
TI  - Tackling drugs moves up EU agenda.

PMID- 9001473
TI  - Incidence of disorders of spermatogenesis in middle aged finnish men, 1981-91:
      two necropsy series.
AB  - OBJECTIVE: To investigate if the incidence of disorders of spermatogenesis and
      testicular tissue morphology have changed in middle aged Finnish men over 10
      years. DESIGN: Two necropsy series completed in 1981 and in 1991. SETTING:
      Department of Forensic Medicine, University of Helsinki, Finland. SUBJECTS: 528
      men, aged 35 to 69 years, subjected to medicolegal necropsy. MAIN OUTCOME
      MEASURES: Scoring of spermatogenesis and morphometric analysis of testicular
      tissue components. Individual risk factors for testicular disorders obtained by
      postmortem blind interviews with acquaintances. RESULTS: Normal spermatogenesis
      was found in 41.7% of the men (mean age 53.1 years). Between 1981 and 1991, the
      ratio of normal spermatogenesis decreased significantly (odds ratio 3.5; 95%
      confidence interval 2.5 to 5.1) from 56.4% to 26.9%, with a parallel increase in
      the incidence of partial and complete spermatogenic arrest (2.1; 1.4 to 2.9 and
      2.9; 1.7 to 5.0, respectively). During this period, the size of seminiferous
      tubules decreased, the amount of fibrotic tissue increased, and the weight of
      testicles decreased significantly. Alterations in testicular characteristics over
      time could not be explained by changes in body mass index, smoking, alcohol
      drinking, or exposure to drugs. CONCLUSIONS: The incidence of normal
      spermatogenesis decreased among middle aged Finnish men from 1981 to 1991, and
      the incidence of disorders of spermatogenesis and pathological alterations in
      testicles increased. Deteriorating spermatogenesis may thus be one important
      factor in the explanation of declining sperm counts observed worldwide.

PMID- 9001474
TI  - Follow up study of moderate alcohol intake and mortality among middle aged men in
      Shanghai, China.
AB  - OBJECTIVE: To assess the risk of death associated with various patterns of
      alcohol intake. DESIGN: Prospective study of mortality in relation to alcohol
      consumption at recruitment, with active annual follow up. SETTING: Four small,
      geographically defined communities in Shanghai, China. SUBJECTS: 18,244 men aged
      45-64 years enrolled in a prospective study of diet and cancer during January
      1986 to September 1989. MAIN OUTCOME MEASURE: All cause mortality. RESULTS: By 28
      February 1995, 1198 deaths (including 498 from cancer, 269 from stroke, and 104
      from ischaemic heart disease) had been identified. Compared with lifelong non
      drinkers, those who consumed 1-14 drinks a week had a 19% reduction in overall
      mortality (relative risk 0.81; 95% confidence interval 0.70 to 0.94) after age,
      level of education, and cigarette smoking were adjusted for. This protective
      effect was not restricted to any specific type of alcoholic drink. Although light
      to moderate drinking (28 or fewer drinks per week) was associated with a 36%
      reduction in death from ischaemic heart disease (0.64; 0.41 to 0.998), it had no
      effect on death from stroke, which is the leading cause of death in this
      population. As expected, heavy drinking (29 or more drinks per week) was
      significantly associated with increased risks of death from cancer of the upper
      aerodigestive tract, hepatic cirrhosis, and stroke. CONCLUSIONS: Regular
      consumption of small amounts of alcohol is associated with lower overall
      mortality including death from ischaemic heart disease in middle aged Chinese
      men. The type of alcoholic drink does not affect this association.

PMID- 9001475
TI  - Underestimation and undertreatment of pain in HIV disease: multicentre study.
AB  - OBJECTIVE: To measure the prevalence, severity, and impact of pain on quality of
      life for HIV patients; to identify factors associated with undertreatment of
      pain. DESIGN: Multicentre cross sectional survey. SETTINGS: 34 HIV treatment
      facilities, including inpatient hospital wards, day hospitals, and ambulatory
      care clinics, in 13 cities throughout France. SUBJECTS: 315 HIV patients at
      different stages of the disease. MAIN OUTCOME MEASURES:  PATIENTS: recorded
      presence and severity of pain and rated quality of life. Doctors: reported
      disease status, estimate of pain severity, and analgesic treatment ordered.
      RESULTS: From 30% (17/56) of outpatients to 62% (73/118) of inpatients reported
      pain due to HIV disease. Pain severity significantly decreased patients' quality
      of life. Doctors underestimated pain severity in 52% (70/135) of HIV patients
      reporting pain. Underestimation of pain severity was more likely for patients who
      reported moderate (odds ratio 24) or severe pain (165) and less likely for
      patients whose pain source was identified or who were perceived as more
      depressed. Of the patients reporting moderate or severe pain, 57% (61/107) did
      not receive any analgesic treatment; only 22% (23/107) received at least weak
      opioids. Likelihood of analgesic prescription increased when doctors estimated
      pain to be more severe and regarded patients as sicker. CONCLUSIONS: Pain is a
      common and debilitating symptom of HIV disease which is gravely underestimated
      and undertreated.

PMID- 9001476
TI  - Randomised comparison of diets for maintaining obese subjects' weight after major
      weight loss: ad lib, low fat, high carbohydrate diet v fixed energy intake.
AB  - OBJECTIVES: To compare importance of rate of initial weight loss for long term
      outcome in obese patients and to compare efficacy of two different weight
      maintenance programmes. DESIGN: Subjects were randomised to either rapid or slow
      initial weight loss. Completing patients were re-randomised to one year weight
      maintenance programme of ad lib diet or fixed energy intake diet. Patients were
      followed up one year later. SETTING: University research department in
      Copenhagen, Denmark. SUBJECTS: 43 (41 women) obese adults (body mass index 27-40)
      who were otherwise healthy living in or around Copenhagen. INTERVENTIONS: 8 weeks
      of low energy diet (2 MJ/day) or 17 weeks of conventional diet (5 MJ/day), both
      supported by an anorectic compound (ephedrine 20 mg and caffeine 200 mg thrice
      daily); one year weight maintenance programme of ad lib, low fat, high
      carbohydrate diet or fixed energy intake diet (< or = 7.8 MJ/day), both with
      reinforcement sessions 2-3 times monthly. MAIN OUTCOME MEASURES: Mean initial
      weight loss and proportion of patients maintaining a weight loss of > 5 kg at
      follow up. RESULTS: Mean initial weight loss was 12.6 kg (95% confidence interval
      10.9 to 14.3 kg) in rapid weight loss group and 12.6 (9.9 to 15.3) kg in
      conventional diet group. Rate of initial weight loss had no effect on weight
      maintenance after 6 or 12 months of weight maintenance or at follow up. After
      weight maintenance programme, the ad lib group had maintained 13.2 (8.1 to 18.3)
      kg of the initial weight loss of 13.5 (11.4 to 15.5) kg, and the fixed energy
      intake group had maintained 9.7 (6.1 to 13.3) kg of the initial 13.8 (11.8 to
      15.7) kg weight loss (group difference 3.5 (-2.4 to 9.3) kg). Regained weight at
      follow up was greater in fixed energy intake group than in ad lib group (11.3
      (7.1 to 15.5) kg v 5.4 (2.3 to 8.6) kg, group difference 5.9 (0.7 to 11.1) kg, P
      < 0.03). At follow up, 65% of ad lib group and 40% of fixed energy intake group
      had maintained a weight loss of > 5 kg (P < 0.07). CONCLUSION: Ad lib, low fat,
      high carbohydrate diet was superior to fixed energy intake for maintaining weight
      after a major weight loss. The rate of the initial weight loss did not influence
      long term outcome.

PMID- 9001477
TI  - Longitudinal study of the effect of apolipoprotein e4 allele on the association
      between education and cognitive decline in elderly men.

PMID- 9001478
TI  - Coma induced by abuse of gamma-hydroxybutyrate (GBH or liquid ecstasy): a case
      report.

PMID- 9001479
TI  - Why don't cancer patients get entered into clinical trials? Experience of the
      Sheffield Lymphoma Group's collaboration in British National Lymphoma
      Investigation studies.

PMID- 9001480
TI  - Counting the cost of social disadvantage in primary care: retrospective analysis
      of patient data.
AB  - OBJECTIVE: To cost the relation between socioeconomic status and various measures
      of primary care workload and assess the adequacy of current "deprivation"
      payments in relation to actual costings for patients living in qualifying areas.
      DESIGN: Retrospective data on primary care were collected over a 4.5 year period
      from both computerised and manually filed records. Standardised data on
      socioeconomic status were obtained by postal questionnaire. SETTING: Inner city
      group practice with a socioeconomically diverse population. SUBJECTS: 382 male
      and female subjects of all ages, with a total of 1296 person years of
      observation. MAIN OUTCOME MEASURES: Primary care costs resulting from
      consultations with a general practitioner or a practice nurse and both new and
      repeat prescriptions. RESULTS: Morbidity, workload, and costs of drug treatment
      increased with decreasing socioeconomic status. The difference in cost for
      patients in social classes IV and V combined compared with those in I and II
      combined was about 150 Pounds per person year at risk (47 Pounds for workload and
      103 Pounds for drugs). Deprivation payments met only half the extra workload cost
      for patients from qualifying wards. CONCLUSIONS: The greater workload caused by
      social disadvantage has been previously underestimated by simple consultation
      rates. The absolute difference in costs for socially disadvantaged patients
      increase as more detailed measures of workload and drug treatment are included.
      Current deprivation payments only partially offset the increased expenditure on
      workload. This shortfall will have to be addressed to attract general
      practitioners to, or retain them in, deprived areas.

PMID- 9001481
TI  - Science, medicine, and the future. Prospecting for gold in the human genome.
AB  - Doctors struggling with the daily problems of clinical medicine usually have
      little time for molecular and cell biology. But genetic research is producing an
      explosion of knowledge which doctors will need to understand in order to join in
      the ethical and financial debates that will inevitably follow the new treatments
      discovered. There may, indeed, be therapeutic gold hidden in our genes, but the
      price for it could be more than we can afford. This is the first of three
      articles introducing a series which aims to convey the excitement and potential
      power of biomedical science by speculating how current research will impinge on
      clinical management of common conditions.

PMID- 9001482
TI  - The future of asthma.
AB  - Reports in the media describing the discovery of "the asthma gene" or "a new
      vaccine for asthma" may be inaccurate and often raise patients' hopes
      unjustifiably. This article is a personal view of key areas in current asthma
      research, and it examines how they may impinge on the care of asthmatic patients
      in the next decade. I have tried to explain the thinking behind some of the
      approaches under study. I discuss the potential contributions of genetic studies,
      immunological approaches, and new therapeutic approaches.

PMID- 9001483
TI  - Lesson of the week. Penetrating intra-oral trauma in children.

PMID- 9001484
TI  - Funding the NHS. Is the NHS underfunded?
AB  - Since 1948 there has been constant debate over whether the NHS is underfunded.
      The debate heats up when crises in the NHS hit the headlines as occurred last
      year. Various groups, of all shades of the political spectrum, have argued that
      the NHS is unsustainable with current funding increases because of demands from
      demographic change, new technology, and increasing expectations. The government
      is almost a lone voice in arguing that the NHS is sustainable but may not be
      doing enough to ensure that it remains so in future. This article examines seven
      broad approaches used to support the case that the NHS is underfunded and
      concludes that all have flaws. There is no satisfactory answer to the question of
      whether the NHS is underfunded because the answer requires value judgments that
      will inevitably give rise to disagreements.

PMID- 9001485
TI  - A difficult case. Childhood onset insulin dependent diabetes presenting with
      severe hyperlipidaemia.
AB  - Confronted with a child deteriorating during treatment of diabetic ketoacidosis,
      Godfrey Nyamugunduru and Helen Roper describe how the child's management was
      complicated by gross hyperlipidaemia. At the point where the child's condition
      was deteriorating despite conventional management we invited two experts-Gilbert
      R Thompson and J I Mann-to suggest a course of action. The original authors then
      describe how they did manage the case, and our experts comment again.

PMID- 9001486
TI  - Cyclists should wear helmets. Increasing the number of cyclists is more
      important.

PMID- 9001487
TI  - Cyclists should wear helmets. Motorists are the cause of the problem.

PMID- 9001488
TI  - Cyclists should wear helmets. Australian laws making helmets compulsory deterred
      people from cycling.

PMID- 9001489
TI  - Cyclists should wear helmets. Better to control the demand for fast cars.

PMID- 9001490
TI  - Cyclists should wear helmets. Health benefits of cycling greatly outweigh loss of
      life years from deaths.

PMID- 9001492
TI  - Looking after elderly sick people is core work in general practice.

PMID- 9001493
TI  - Midwives can help increase uptake of antenatal screening for HIV.

PMID- 9001494
TI  - When is referral of Heaf test positive schoolchildren worth while? More data are
      needed.

PMID- 9001495
TI  - When is referral of Heaf test positive school children worth while? Evidence is
      not sufficiently persuasive to overturn current recommendation.

PMID- 9001496
TI  - Statistical basis of public policy. Epidemiology does not need Bayesian
      inference.

PMID- 9001497
TI  - Statistical basis of public policy. Qualitative and quantitative aspects should
      not be confused.

PMID- 9001499
TI  - Statistical basis of public policy. Bayesian analysis should be used instead of
      league tables of performance.

PMID- 9001498
TI  - Statistical basis of public policy. Present remembrance of priors past is not the
      same as a true prior.

PMID- 9001500
TI  - Statistical basis of public policy. Bayesian statistics is valuable provided it
      is based on data.

PMID- 9001502
TI  - Bowel preparation at home in elderly people. Give a simultaneous infusion of
      saline in frail patients.

PMID- 9001501
TI  - Bowel preparation at home in elderly people. Patients should be warned not to
      drink too much or too little fluid.

PMID- 9001503
TI  - What is the prior probability of a proposed new treatment being superior to
      established treatments?

PMID- 9001505
TI  - Surgery for mental illness has been proved effective.

PMID- 9001504
TI  - Oral contraceptives are drug of choice for menorrhagia in the Netherlands.

PMID- 9001506
TI  - Doctors' retainer scheme. Time limit of five years may be too short for some
      doctors.

PMID- 9001507
TI  - Doctors' retainer scheme. Should be more widely available in hospital practice.

PMID- 9001508
TI  - Results of American and European studies of thrombolysis in acute stroke are not
      conflicting.

PMID- 9001510
TI  - Assuming that developing countries could not afford xenotransplantation is
      patronising.

PMID- 9001509
TI  - Charity has published information booklet about clinical trials in cancer.

PMID- 9001511
TI  - BMA asks for 53% pay increase. Morality of such claims is doubtful in light of
      growing disparity in society.

PMID- 9001512
TI  - BMA asks for 53% pay increase. General practitioners want parity with hospital
      consultants.

PMID- 9001543
TI  - Pacemakers.
AB  - Rapid advances in pacing technology will continue to affect the quality of life
      of many patients with cardiovascular disease. A truly "smart" device that seemed
      fanciful 30 years ago now seems to be a virtual certainty by early in the next
      century. The surgical contributions and expertise of individuals trained in
      cardiothoracic surgery in these bradypacing developments is highly desirable to
      minimize morbidity to the greatest possible degree, to optimize the outcome of
      the procedure for the individual patient, and to conserve health care costs as
      much as possible. To maintain this cardiothoracic presence in cardiac pacing,
      acquisition of knowledge and expertise in the basic electrophysiology and
      technology of cardiac pacing, to go along with surgical expertise, is necessary
      on the part of individuals with the interest and opportunity to do so.

PMID- 9001544
TI  - Transplantation of encapsulated cells and tissues.

PMID- 9001545
TI  - Laparoscopic ultrasonography for staging gastroesophageal cancer.
AB  - BACKGROUND: TNM staging of gastroesophageal cancer is improved by the use of
      laparoscopy for the detection of occult metastases and endoscopic ultrasonography
      for T and possibly N staging. Laparoscopic ultrasonography may combine the
      strengths of both of these techniques. The purpose of this study was to compare
      TNM staging by means of laparoscopic ultrasonography (Lap US), laparoscopy, and
      conventional computed tomography (CT). METHODS: TNM stage was determined by using
      Lap US, laparoscopy, and CT scanning in 26 surgical candidates with gastric or
      esophageal cancer in a blinded fashion. CT scans were also reviewed separately by
      an expert radiologist. Validation of findings was by means of final pathologic
      examination. RESULTS: Resectability for potential cure was determined by means of
      Lap US with a sensitivity of 100% and a specificity of 91% versus 100% and 73%
      for laparoscopy and 75% and 60% for CT, respectively. Overall TNM staging was 82%
      accurate for Lap US versus 67% for laparoscopy and 47% for CT (chi-squared, 8.64,
      p < 0.005, and 10.4, p < 0.005, respectively). Accuracies for Lap US versus
      laparoscopy versus CT for N stage were 92% versus 84% versus 70%, respectively,
      for T stage were 92% versus 42% versus 60%, respectively, and for M stage were
      89% versus 44% versus 62%, respectively. CONCLUSIONS: T and N staging by Lap US
      were comparable to published results for endoscopic ultrasonography, and overall
      TNM staging was better. Lap US may provide the optimal preoperative staging for
      gastric cancer and has the potential to complement endoscopic ultrasonography in
      staging esophageal cancer.

PMID- 9001546
TI  - Laparoscopic versus open splenectomy for immune thrombocytopenic purpura.
AB  - BACKGROUND: We sought to determine whether laparoscopic techniques can reduce the
      operative morbidity of surgery in patients undergoing splenectomy for immune
      thrombocytopenic purpura (ITP). METHODS: All patients (60) undergoing splenectomy
      for ITP at the Royal Adelaide Hospital from January 1985 to November 1995 were
      reviewed. Results of patients undergoing open operation were obtained by means of
      retrospective case note review, whereas details of all patients undergoing
      laparoscopic splenectomy were collected prospectively and maintained on a
      computerized database. RESULTS: Forty-seven patients underwent splenectomy with
      an open technique and 13 with a laparoscopic technique. Patient groups were
      demographically similar. All laparoscopic procedures were completed with the
      laparoscopic technique. An accessory spleen was also removed at laparoscopic
      operation from two (15%) patients and at open operation from three patients (6%).
      Two more accessory spleens were missed at the original procedure, one at open
      operation and one at laparoscopic operation. These required later removal by
      using open and laparoscopic techniques, respectively. Blood and platelet
      transfusion requirements were reduced by the laparoscopic approach. Although mean
      operating times were similar (87 versus 88 minutes), laparoscopic splenectomy was
      associated with a greatly reduced postoperative hospital stay (10 versus 2 days,
      median; p < 0.0001) and no major morbidity. Long-term normalization of platelet
      counts was similar for the two techniques. The laparoscopic approach resulted in
      a reduction in hospital treatment costs from $4224 to $2238 per case (cost
      savings of $1986 per case). CONCLUSIONS: Laparoscopic splenectomy results in
      improved clinical outcomes and reduced costs for patients undergoing elective
      splenectomy for ITP.

PMID- 9001548
TI  - Radical resection of tumors of the inferior vena cava with vascular
      reconstruction and kidney autotransplantation.
AB  - BACKGROUND: Tumors of the inferior vena cava (IVC) are rare tumors. Although
      often locally confined, juxtaposed vital structures usually limit the extent of
      resection. However, complete surgical resection has been shown to be the most
      important positive prognostic factor. METHODS: Four patients had resection of
      primary vena caval tumors. In two patients with locally extensive vena caval
      tumors the limits of conventional resection were extended by means of complete
      resection of the involved infrahepatic IVC, aorta, and both kidneys. The IVC and
      aorta were reconstructed with synthetic grafts, and the uninvolved kidney was
      autotransplanted for both patients. RESULTS: Of the two patients treated with
      more extensive resection, one patient had no evidence of disease 26 months after
      operation, and the second patient died of recurrent disease 23 months after
      operation. CONCLUSIONS: Primary tumors of the IVC may extend locally without
      distant metastasis. Radical surgical excision as the primary mode of treatment
      provides the best chance for prolonged survival in appropriately selected
      patients with tumors of the IVC. After surgical excision the patient with the
      leiomyosarcoma was treated with radiation therapy and the patient with
      rhabdomyosarcoma by chemotherapy. Although leiomyosarcomas of the IVC are rare
      tumors, the first patient is only the third reported case of the even rarer
      rhabdomyosarcoma of the IVC.

PMID- 9001547
TI  - Differing roles of nitric oxide in the pathogenesis of acute edematous versus
      necrotizing pancreatitis.
AB  - BACKGROUND: Microcirculatory changes and leukocyte-endothelial interaction are
      both central to the pathogenesis of acute pancreatitis. We studied the effects of
      nitric oxide (NO) donors (intravenous or inhaled) and NO inhibitors, which affect
      each of these processes, on markers of experimental mild (edematous) and severe
      (necrotizing) pancreatitis in rats. METHODS: Mild pancreatitis was induced with
      intravenous cerulein (n = 100) and severe pancreatitis with intravenous cerulein
      and intraductal glycodeoxycholic acid (n = 100). Each group was randomly divided
      into five equal treatment subgroups: control, NO-synthase substrate L-arginine,
      NO donor sodium nitroprusside, NO-synthase inhibitor N-nitro-L-arginine methyl
      ester (L-NAME), and NO-inhalation. After 6 hours edema was measured by a wet/dry
      weight ratio, and pancreatic injury was quantified by tissue levels of
      trypsinogen activation peptides (TAPs) and by histologic analysis of inflammation
      and necrosis. RESULTS: In mild pancreatitis (1) both NO donors reduced edema
      formation (p < 0.001) and also reduced intrapancreatic TAPs (p < 0.03); (2) L
      NAME significantly increased tissue TAPs (p < 0.03); and (3) inhaled NO had no
      effect. In severe pancreatitis (1) both intravenous NO donors reduced edema
      formation (p < 0.005) and both markedly reduced intrapancreatic TAPs (p < 0.001);
      (2) L-NAME did not further increase the already high tissue TAPs; and (3) inhaled
      NO decreased tissue TAPs (p = 0.01). Evaluation of inflammation and necrosis by
      histologic scoring confirmed the reduction of pancreatic injury by NO donors and
      worsening with NO-synthase inhibitor. CONCLUSIONS: NO donors have a beneficial
      effect on edema formation in acute pancreatitis but confer more important
      protection against ectopic trypsinogen activation, which correlates with
      mortality, inflammation, and necrosis. Although direct microcirculatory action is
      likely, the salutary effect of inhaled NO in severe pancreatitis may suggest
      indirect action on circulating leukocytes, which are thought to potentiate tissue
      injury.

PMID- 9001549
TI  - Selective surgical indications for iatrogenic hemobilia.
AB  - BACKGROUND: This study was undertaken to assess the place for surgery in patients
      with iatrogenic hemobilia. METHODS: Nineteen patients were treated for hemobilia
      caused by percutaneous liver biopsy (n = 11), percutaneous transhepatic
      cholangiography (PTC, n = 5), or percutaneous biliary drainage (PBD, n = 3).
      Selective embolization was attempted in all patients who bled after percutaneous
      liver biopsy or PTC but one, whereas irrigation via the external catheter was
      tried first in patients bleeding after PBD. RESULTS: Selective embolization was
      successful in 13 cases (87%) of 15. Technical impossibility of selective
      embolization (n = 2) and absence of recognizable vascular lesion (n = 1) were the
      reasons for surgery in three actively bleeding patients. Indications for delayed
      surgery included hemocholecystitis (n = 3) and inadvertent embolization of the
      gallbladder (n = 1). Biliary decompression was only required after PTC and was
      achieved by endoscopic sphincterotomy (n = 3), percutaneous transtumoral
      intubation (n = 1), or surgery (n = 1) after failure of percutaneous biliary
      dilation. After PBD, repeat irrigation and tube replacement were used to stop the
      bleeding and to decompress the biliary tract without embolization or surgery.
      None of the 19 patients died, and none experienced recurrent bleeding.
      CONCLUSION: Surgical indications for iatrogenic hemobilia are limited and include
      failure or complication of arterial embolization, hemocholecystitis, and failed
      attempt at endoscopic or percutaneous biliary decompression in case of
      obstructive jaundice.

PMID- 9001550
TI  - Analysis of K-ras oncogene mutations in chronic pancreatitis with ductal
      hyperplasia.
AB  - BACKGROUND: K-ras oncogene mutations have been identified in up to 95% of
      pancreatic cancers, implying their critical role in their molecular pathogenesis.
      However, the earliest stage in which K-ras mutations can be detected in potential
      precursor lesions of pancreatic cancer remains unclear. This study evaluates
      pancreatic ductal hyperplasia in the setting of chronic pancreatitis, which
      predisposes to pancreatic cancer development, for K-ras codon 12 and 13
      mutations. METHODS: Paraffin-embedded surgical specimens from 42 patients with
      chronic pancreatitis were examined microscopically for the presence of ductal
      hyperplasia. Both hyperplastic and nonhyperplastic ducts were microdissected from
      the specimens that contained hyperplasia (11 of 42). Four of the remaining
      specimens without hyperplasia served as controls. Genomic DNA was extracted, and
      polymerase chain reaction and amplification of the K-ras oncogene was performed.
      Polymerase chain reaction products were evaluated by means of hybridization to
      mutant specific oligonucleotide probes and by means of automated DNA sequencing.
      RESULTS: K-ras codon 12 mutations representing glycine to valine substitutions
      were present in 2 of (18%) 11 patients with ductal hyperplasia. No mutations were
      found in the controls without ductal hyperplasia. CONCLUSIONS: Our study supports
      the premise that K-ras mutations develop in a subset of chronic pancreatitis
      associated hyperplasia and provides a genetic basis for the potential progression
      of chronic pancreatitis to pancreatic cancer.

PMID- 9001551
TI  - An improved process for development and testing of vena caval filters: the
      percutaneous steel Greenfield filter.
AB  - BACKGROUND: The purpose of this study was to develop a reduced profile stainless
      steel Greenfield filter with an over-the-wire delivery system and to compare its
      performance with the existing Food and Drug Administration-approved Greenfield
      filters. In addition, we wanted to standardize a system for evaluating filter
      prototypes. METHODS: Percutaneous stainless steel filters with various hook
      configurations were evaluated for efficacy and safety in four in vitro modules
      designed to reproduce potential liabilities experimentally. Animal studies to
      assess thrombus capture and resolution, filter stability, migration, and
      hemodynamics were completed in 4 dogs and 38 sheep. RESULTS: Mathematical
      modeling suggested that hook angle was the most relevant factor in improving
      resistance to migration. Prototypes that varied with respect to hook length and
      angle were evaluated in both the in vitro testing unit and in sheep. The
      stainless steel filter with two downward directed hooks provided clot capture
      comparable with the current Greenfield filter, maintenance of flow, and
      resistance to fatigue and corrosion while providing significant resistance to
      migration and penetration (p < 0.05). CONCLUSIONS: The percutaneous stainless
      steel Greenfield filter with the alternating hook design provides a reduced
      profile device that can be placed over a wire to improve positioning. The use of
      a standardized testing system reduced both the time and cost of bringing this new
      device to the market.

PMID- 9001552
TI  - High coincidence of Mirizzi syndrome and gallbladder carcinoma.
AB  - BACKGROUND: Mirizzi syndrome is a rare complication of long-standing
      cholelithiasis. It is defined as obstructive jaundice caused by external
      compression of the common hepatic duct by an impacted stone in the gallbladder
      neck. Gallstone disease and cholelithiasis-associated chronic biliary
      inflammation may play a causative role in the pathogenesis of gallbladder
      carcinoma. The purpose of this study was to investigate the coincidence of
      gallbladder carcinoma associated with Mirizzi syndrome. Furthermore, the
      diagnostic value of elevated CA 19-9 levels as indicator for a coincidental
      gallbladder carcinoma in this syndrome was studied. METHODS: Patient
      demographics, clinical findings, laboratory data, results of diagnostic studies,
      pathologic reports, and intraoperative findings of 1579 patients undergoing
      cholecystectomy were obtained from patient records and were retrospectively
      studied. Only patients with proven Mirizzi syndrome (i.e., extrinsic mechanical
      compression of the common hepatic duct by impacted gallstones, associated chronic
      cholecystitis, and a history of jaundice) were included in this study. RESULTS:
      Eighteen cases of Mirizzi syndrome (1.0%) out of 1759 cholecystectomies performed
      between January 1986 and March 1995 were identified. The seven male patients and
      11 female patients had an average age of 74.8 years (range, 32 to 87 years). In
      five of these patients (27.8%) coincidental cases of gallbladder carcinoma were
      detected. The incidence of unsuspected malignancies in long-standing gallstone
      disease was 36 (2%) of 1759 and was statistically significantly different (p <
      0.001) from the incidence in patients with Mirizzi syndrome (27.8%, 5 of 18). No
      significant difference was noted in age, gender, duration of jaundice, and type
      of lesions between these two groups. Tumor-associated antigen CA 19-9 level was
      elevated in 12 patients with Mirizzi syndrome, but it was significantly higher (p
      < 0.0001) in all five patients with coincidental gallbladder neoplasm and peaked
      at 1000 units/ml. All patients diagnosed with gallbladder carcinoma died within
      18 months after operation. CONCLUSIONS: There is high association of gallbladder
      cancer in Mirizzi syndrome. Elevated CA 19-9 levels in this syndrome are
      indicative of a coincidental gallbladder malignancy. Because of this high
      coincidence of Mirizzi syndrome and gallbladder cancer we recommend an
      intraoperative frozen section of the gallbladder in all patients presenting with
      Mirizzi syndrome.

PMID- 9001554
TI  - Pneumoperitoneum with carbon dioxide stimulates growth of malignant colonic
      cells.
AB  - BACKGROUND: Port-site recurrences have often been reported after laparoscopic
      surgery for malignant disease, and the pathogenesis is unknown. Whether different
      gases used to establish pneumoperitoneum have an influence on tumor cell growth
      has not been investigated. METHODS: Tumor growth of colon adenocarcinoma
      DHD/K12/TRb was measured in a rat model after insufflation with either carbon
      dioxide or helium and in a control group. Tumor growth was evaluated in three
      experiments: (1) in vitro (n = 60), (2) ex vivo (n = 60), and (3) in vivo (n =
      60). After insufflation, cell kinetics were determined in the first two
      experiments. In the third experiment, tumor growth was measured subcutaneously
      and intraperitoneally 5 weeks after insufflation. RESULTS: Tumor cell growth
      increased significantly after insufflation with carbon dioxide in vitro (p <
      0.03) and ex vivo (p < 0.05) compared with the control group, whereas helium did
      not stimulate cell growth. In vivo, subcutaneous tumor growth was promoted by
      carbon dioxide (131 +/- 55 mg) (p < 0.01) compared with helium (35 +/- 34 mg) and
      the control group (36 +/- 33 mg). Total intraperitoneal tumor weight was 717 +/-
      320 mg in carbon dioxide group compared with helium (549 +/- 231 mg) and control
      group (570 +/- 321 mg). CONCLUSIONS: The insufflation of carbon dioxide promotes
      tumor growth compared with helium and control in a rat model. Further studies
      should confirm these results before alternative gases should be recommended in
      laparoscopic surgery for malignant diseases.

PMID- 9001553
TI  - Short-term preservation of autogenous vein grafts: effectiveness of University of
      Wisconsin solution.
AB  - BACKGROUND: Suboptimal preservation of autologous veins in storage solutions
      causes endothelial cell damage that can contribute to graft failure. The purpose
      of this study was to compare the effects of short-term storage of veins in
      autologous whole blood (AWB), 0.9% normal saline solution (NS), and University of
      Wisconsin solution (UWs) on vein structure and function after grafting. METHODS:
      Autogenous jugular and femoral veins were atraumatically harvested from mongrel
      dogs. One vein segment was immediately implanted to serve as a control, and the
      other segments were stored for 45 minutes in AWB, NS, or UWs. The veins were
      implanted as reversed interposition graft in the carotid or femoral arteries.
      After 6 weeks light and scanning electron microscopy and isometric tension
      studies were performed on explanted vein grafts. RESULTS: Morphologic studies
      revealed an intact endothelium that stained positively for factor VIII. Intimal
      thickness was similar between controls (48 +/- 12 microns) and veins stored in
      UWs (53 +/- 8 microns) (p = not significant), but it was significantly increased
      in veins stored in AWB (151 +/- 29 microns) and NS (149 +/- 18 microns) (p <
      0.05). Sensitivity and maximum contraction to norepinephrine were not altered in
      veins preserved in UWs (6.0 +/- 0.1 mumol/L and 0.19 +/- 0.02 gm/mm2) but were
      significantly reduced (p < 0.05) in those stored in AWB (7.2 +/- 0.1 mumol/L and
      0.08 +/- 0.02 gm/mm2) and NS (7.0 +/- 0.3 mumol/L and 0.09 +/- 0.02 gm/mm2)
      compared with controls (5.9 +/- 0.2 mumol/L and 0.20 +/- 0.02 gm/mm2). The
      sensitivity and maximum relaxation to acetylcholine and sodium nitroprusside of
      veins preserved in AWB, NS, and UWs were similar to controls (p = not
      significant). CONCLUSIONS: Vein storage in UWs preserves smooth muscle cell
      function compared with veins stored in NS or AWB. Therefore UWs is a more
      suitable medium for short-term preservation of veins in cardiovascular operation.

PMID- 9001555
TI  - Donor-specific unmodified bone marrow transfusion does not facilitate intestinal
      engraftment after bowel transplantation in a porcine model.
AB  - BACKGROUND: The immunosuppression required to prevent rejection of intestinal
      transplants causes a high rate of infection and lymphoma. It is crucial that
      immunomodulatory strategies be developed to facilitate intestinal engraftment.
      METHODS: We prospectively examined the effect of unpurified donor-specific bone
      marrow transfusions (DSBMTs) on rejection, infection, graft-versus-host disease
      (GVHD), and survival after intestinal transplantations in 44 Yorkshire Landrace
      pigs. Four groups that differed according to presence or abscence of treatment
      with FK506 and DSBMT were analyzed. RESULTS: In nonimmunosuppressed pigs, DSBMTs
      had no effect on survival (8 days versus 9 days in controls; p = 0.9). In FK506
      pigs, DSBMTs tended to reduce survival (21 days versus 37 days in FK506 controls;
      p = 0.1); no difference was seen between two bone marrow dosages 5 x 10(7) or 5 x
      10(8) bone marrow cells/kg. No difference in the incidence of death caused by
      rejection was seen between DSBMTs and controls, but there was a marked tendency
      toward more deaths caused by rejection in DSBMTs + FK506 versus FK506-only pigs
      (p = 0.09). Daily stomal assessment showed a higher rate of moderate and severe
      interstitial rejection in DSBMT + FK506 versus FK506-only pigs; DSBMT was also
      associated with increased vascular rejection. Finally, groupwise comparison
      showed an order of susceptibility to lethal GVHD and infection as follows: DSBMT
      + FK506 > FK506 > DSBMT > controls. CONCLUSIONS: Rather than promoting
      engraftment, DSBMT can sensitize recipients and cause rejection after intestinal
      transplantation. It aggravates the risks of generalized GVHD and infection and
      tends to reduce graft and recipient survival. Before being applied clinically,
      DSBMT needs to be refined to increase its tolerogenic potential without causing
      GVHD.

PMID- 9001557
TI  - Does the direction of portal blood flow determine outcome with small-diameter
      prosthetic H-graft portacaval shunt?
AB  - BACKGROUND: Partial portal decompression, as attained by small-diameter
      prosthetic H-graft portacaval shunting, continues to gain popularity because of
      favorable outcomes. This study was undertaken to determine whether the direction
      of preshunt or postshunt portal blood flow or reversal in the direction of portal
      flow occurred with shunting effect outcome after small-diameter prosthetic H
      graft portacaval shunt. METHODS: In 56 consecutive patients the direction of
      portal flow was determined before and after shunting. The direction of portal
      blood flow before and after shunting and changes in the direction of portal flow
      that occur with shunting were correlated with 30-day and 1-year survival, as well
      as with the rate of postshunt encephalopathy. RESULTS: Portal pressures
      significantly decreased in all with shunting. Whether or not stratified by
      Child's classification, neither the preshunt nor postshunt direction of portal
      flow affected 30-day or 1-year survival or incidence of encephalopathy. Eleven
      patients (significant at p < 0.001, fisher's exact test) had reversal of portal
      blood flow with shunting without an increase in 30-day or 1-year survival or
      incidence of encephalopathy. CONCLUSIONS: Small-diameter prosthetic H-graft
      portacaval shunts significantly reduce portal pressure and lead to reversal of
      portal flow in significant numbers. Significant hepatic dysfunction is uncommon
      after shunting. Neither the direction of preshunt or postshunt portal blood flow
      nor the reversal of portal blood flow with shunting has an effect on clinical
      outcome after small-diameter prosthetic H-graft portacaval shunt.

PMID- 9001556
TI  - Whole gut washout for severe sepsis: review of technique and preliminary results.
AB  - BACKGROUND: The purpose of this study was to determine the safety and feasibility
      of whole gut washout for severe sepsis in human beings. METHODS: High-volume
      polyethylene glycol-3500 was administered to patients with severe sepsis. Body
      temperature, white blood cell count, and ventilatory indexes were recorded 24
      hours before and 24 hours after whole gut washout. RESULTS: A significant
      decrease in febrile response was observed after gut washout with polyethylene
      glycol. Improvements in PaO2, positive end-expiratory pressure, and peak airway
      pressure were observed. The washout was well tolerated in all but one patient.
      CONCLUSIONS: High-volume whole gut washout for severe sepsis appears safe in
      critically ill patients and may offer some promise in reducing enterogenic
      inflammation after catabolic stress.

PMID- 9001558
TI  - Lymphatic mapping and epitrochlear lymph node dissection for melanoma.

PMID- 9001560
TI  - Second ipsilateral breast cancer after modified radical mastectomy: a case report
      and review of the literature.

PMID- 9001559
TI  - Portal vein aneurysm: a rare but important vascular condition.

PMID- 9001561
TI  - Percutaneous versus standard tracheostomy.

PMID- 9001562
TI  - Interpretability of a clinical measure.

PMID- 9001563
TI  - Extraperitoneal prosthetic mesh for repair of pelvic hernias.

PMID- 9001564
TI  - Paul W. Harrison and herniology.

PMID- 9001565
TI  - Carcinoembryonic antigen as a target for cancer vaccines.
AB  - The vaccine approach to cancer therapy is still in the early stages. Since any
      immune response has a limited capacity, immunotherapeutic manipulations to
      destroy tumor will probably be most effective against small tumor masses or
      micrometastases. Consequently, immunotherapy with these CEA cancer vaccines may
      prove most effective in the adjuvant setting, where disease has been controlled
      or stabilized with conventional therapies. The development of CEA cancer vaccines
      involves many parameters, including the appropriate form of the vaccine, i.e.,
      recombinant protein, peptides, vectors etc., the use of classical adjuvants
      and/or biological adjuvants such as cytokines, and the use of T cell
      costimulatory molecules. The integration of these parameters into the development
      of a cancer vaccine will be the challenge for the next decade [33].

PMID- 9001566
TI  - Oncogene products represent potential targets of tumor vaccines.

PMID- 9001567
TI  - Making the most of mucin: a novel target for tumor immunotherapy.
AB  - Throughout this brief review I have emphasized the unique biochemical and
      immunological properties of MUC-1 mucin that make this tumor-associated antigen a
      novel, exciting and tangible target for tumor immunotherapy. The tandemly
      repeating nature of the antigenic epitopes in the mucin polypeptide chain, the
      under-glycosylation of these epitopes, and the expression of the molecule at the
      cell surface, are all central to the immune recognition of this antigen and must
      be acknowledged in the design of MUC-1 vaccines. There are considerable
      difficulties associated with such a design. Short, immunogenic peptides that
      associate with MHC class I molecules on the cell surface to induce CTL responses
      are not useful here; MUC-1 must be expressed at the cell surface and this
      introduces the numerous problems associated with gene transfer. Furthermore,
      generating under-glycosylated mucin molecules that resemble tumor-associated
      antigen is not trivial. Competitive inhibition of glycosylation with PhGalNAc is
      often incomplete, and merely increasing inhibitor concentration results in cell
      toxicity. But treating tumors is also not trivial. MUC-1 mucin has many
      characteristics of the ideal tumor-associated antigen, and our understanding of
      the unique mechanism of mucin recognition on tumors and the appropriate vaccine
      designs to target this antigen is now advanced. Transgenic mouse and non-human
      primate models provide excellent preclinical models to test immunotherapeutic and
      vaccine strategies, and in vitro studies and early-stage clinical trials in
      humans provide considerable cause for optimism. The next few years in this field
      should certainly be productive.

PMID- 9001568
TI  - Carbohydrate antigens as targets for active specific immunotherapy.
AB  - Carbohydrate antigens such as GM2, GD2 and GD3 (gangliosides), Lewis(y) and globo
      H (neutral glycolipids and glycoproteins), and Tn, TF and sTn (glycoproteins) are
      overexpressed in a variety of cancers. Antibodies against several of these
      carbohydrate antigens have been detected in sera from patients treated with
      cancer vaccines, and have been associated with a more favorable prognosis.
      Clinical responses have been reported after treatment with monoclonal antibodies
      against some of these antigens. Hence cell-surface carbohydrate antigens have
      been identified as suitable targets for immune attack by both active and passive
      immunotherapies. Different approaches have been adopted to induce immune
      responses against these carbohydrate antigens. These includes vaccination with
      whole or lysed tumor cells, purified or synthetic carbohydrates, immunogenic
      carbohydrate derivatives, or carbohydrates conjugated with immunogenic carriers
      and administered with immunological adjuvants. In the case of gangliosides,
      immunization with either whole tumor cells or cell lysates has only occasionally
      induced responses against carbohydrate antigens, and the antibodies were
      generally IgM antibodies of low titer. Compared with other methods of
      vaccination, conjugate vaccines have consistently induced the highest titer of
      IgM and IgG antibodies against gangliosides and other carbohydrate antigens.
      Preclinical and clinical studies with conjugate carbohydrate vaccines have
      induced IgM and IgG antibody responses capable of inducing complement-mediated
      cytotoxicity of tumor cells in vitro and associated with prolonged disease-free
      and overall survival in patients.

PMID- 9001569
TI  - Dendritic cells presenting tumor antigen.
AB  - Since the first identification of dendritic cells by Steinman and Cohn in 1973,
      progress in understanding their biology has included the development of novel
      methods of cell culture, recognition of critical aspects of migration and
      maturation, and appreciation of their major role as antigen-presenting cells
      (APC), and how this activity is regulated by cytokines and expression of
      accessory molecules. Dendritic cells are the major APC involved in the initiation
      of the immune response and the development of tolerance. There is considerable
      evidence that they can acquire antigen in the peripheral tissues and process,
      transport, and present it to T cells in secondary lymphoid tissue. A number of
      studies show that, in vitro or in vivo, antigen-pulsed dendritic cells can
      directly sensitize T cells and stimulate the development of antigen-specific
      immune responses, including both protective and therapeutic antitumor responses.
      In this paper, several important aspects of dendritic cell biology are discussed
      and a number of studies confirming the role of these professional APC in
      antitumor immunity are reviewed.

PMID- 9001571
TI  - Active specific immunotherapy with hapten-modified autologous melanoma cell
      vaccine.
AB  - We have developed a novel approach to cancer immunotherapy-an autologous whole
      cell vaccine modified with the hapten dinitrophenyl (DNP). This approach elicits
      significant inflammatory responses in metastatic sites and some objective tumor
      responses. Post-surgical adjuvant immunotherapy with DNP-modified melanoma
      vaccine in a setting of micrometastatic disease produces significant survival
      prolongation in stage III melanoma patients. Histologically, the inflammatory
      responses of the tumor consist of infiltration by lymphocytes, the majority of
      which are CD8+, HLA-DR+ T cells. T cells from these lesions tend to have mRNA for
      interferon gamma. T cell receptor analysis suggests that the tumor-infiltrating T
      cells are clonally expanded. DNP-modified vaccine also induces T cells in the
      peripheral blood, which respond to DNP-modified autologous cells in a hapten
      specific, MHC-restricted manner. Moreover, a T cell line generated from these
      lymphocytes responded to only a single HPLC fraction of MHC-associated, DNP
      modified tumor peptides. Since inflammatory responses in metastases were not
      consistently associated with dramatic tumor regression, we considered the
      possibility of immunosuppression at the tumor site. We found that mRNA for the
      anti-inflammatory cytokine, interleukin-10 (IL-10) is expressed in most
      metastatic melanoma tissues and subsequently demonstrated that IL-10 protein is
      produced by melanoma cells. Thus the efficacy of DNP vaccine could be further
      enhanced by inhibition of IL-10 production or binding. Finally, we expect these
      results obtained with melanoma to be applicable to other human cancers.

PMID- 9001570
TI  - Gene-modified tumor cells as cellular vaccine.
AB  - The identification and characterization of many tumor antigens and the parallel
      explosion of knowledge of the cellular and molecular mechanisms of antigen
      recognition by the immune system have given renewed hopes that immunogenetherapy
      could be a promising modality to treat certain tumors. Many different novel
      strategies have been developed to derive genetically modified tumor cells and use
      them as cellular vaccines to induce useful antitumor immunity in a variety of
      animal tumor models. This review discusses induction of tumor immunity by
      injecting tumor cells that are genetically engineered to secrete various
      cytokines and to express major histocompatibility complex molecules and/or
      costimulatory molecules. While there has been a great success in inducing
      excellent antitumor immunity in a variety of tumor models, there are some
      difficulties and limitations in the application of these gene-modified tumor
      cells for the treatment of preexisting tumors. A number of improvements and
      modifications are already underway to overcome some of these problems.

PMID- 9001572
TI  - Treatment of malignancy by direct gene transfer of a foreign MHC class I
      molecule.

PMID- 9001573
TI  - Immunogenicity increase of autologous tumor cell vaccines by virus infection and
      attachment of bispecific antibodies.
AB  - A new type of cancer vaccine for therapeutic application in cancer patients is
      described. It consists of three components. (1) autologous tumor cells, (2)
      Newcastle Disease Virus (NDV), to be used for infection and (3) bispecific
      antibodies (bsAb) which attach to the viral hemagglutinin neuraminidase (HN)
      molecule on the infected tumor cells. A standardized procedure has been developed
      for generating virus infected human autologous tumor cell vaccines (ATV-NDV)
      which includes cell dissociation, removal of leukocytes and cell debris, gamma
      irradiation and cryopreservation. Infection with the non-virulent strain NDV
      Ulster is performed within 30 min of co-incubation. While virus infection already
      increased immunogenicity of the tumor vaccine, further augmentation of T cell
      stimulatory capacity is achieved by attachment of specially designed bi-specific
      antibodies (bs HN x CD28 or bs HN x CD3).

PMID- 9001574
TI  - Radiation induced chromosomal aberrations. Introduction.

PMID- 9001575
TI  - DNA lesions and repair.

PMID- 9001576
TI  - Insight into sites.
AB  - Spatial factors conditioning the formation of radiation-induced chromosome
      exchange aberrations are reviewed, and concepts such as 'rejoining distance' and
      'site' are re-examined in the light of the unexpectedly high frequencies of multi
      break ('Complex') exchanges being revealed by FISH painting. Given the
      anticipated densities of dsb within a nucleus, and assuming random 3-D break
      distribution, nearest-neighbour analysis indicates that the most likely break
      interaction distance is a well defined shell, several hundred nm from each break.
      The sharpness with which this shell is defined increases with break density, and
      therefore with dose. It is argued that random movement and chance meeting over
      such distances will not account for the Complex frequencies observed, and that
      other factors, or modes of formation, must be invoked.

PMID- 9001578
TI  - Mechanisms of radiation-induced chromosome aberrations.

PMID- 9001577
TI  - Nuclear architecture and the induction of chromosomal aberrations.
AB  - Progress in fluorescence in situ hybridization, three dimensional microscopy and
      image analysis has provided the means to study the three-dimensional structure
      and distribution of chromosome territories within the cell nucleus. In this
      contribution, we summarize the present state of knowledge of the territorial
      organization of interphase chromosomes and their topological relationships with
      other macromolecular domains in the human cell nucleus, and present data from
      computer simulations of chromosome territory distributions. On this basis, we
      discuss models of chromosome territory and nuclear architecture and topological
      consequences for the formation of chromosome exchanges.

PMID- 9001579
TI  - The involvement of telomeric sequences in chromosomal aberrations.
AB  - Three functional elements are required for the stable transmission of eukaryotic
      chromosomes: replication origins, centromeres and telomeres. In the yeast
      Saccharomyces cerivisiae the DNA sequences defining each of these elements are
      known. The simplest and most widely conserved of these sequences is that of the
      telomere. As the name implies, the telomere is the end of a linear eukaryotic
      chromosome. Two of the main functions of the telomere are to prevent DNA loss as
      a consequence of replication and to prevent interactions with other chromosomal
      ends. Thus, telomeres play a major role in maintaining chromosome stability and
      consequently they have been considered as likely to be involved in some aspects
      of chromosomal aberration formation. The involvement of telomeric DNA sequences
      in stabilizing normal and broken chromosome ends, in "hot spots' for aberration
      formation and in delayed chromosomal instability will be reviewed here drawing on
      material presented at the Workshop and the published literature.

PMID- 9001580
TI  - Adaptive response to ionizing radiation in human lymphocytes: the problem of
      scoring aberrations in cells irradiated during asynchronous growth.

PMID- 9001581
TI  - DNA content proportionality and persistence of radiation-induced chromosomal
      aberrations studied by FISH.
AB  - Chromosome aberrations induced by radiation have been used for the purpose of
      dosimetry for a long time. Translocations are especially useful for retrospective
      dosimetry, since they are assumed to be stable. The method of chromosome painting
      (FISH) has facilitated objective scoring of aberrations considerably.
      Translocation frequencies, obtained by FISH, for retrospective dosimetry rely on
      the main assumptions of neutral selection value and that the distribution of
      aberrations over the chromosomes is a known function of the DNA content of the
      chromosomes. Data scrutinising the two above-mentioned assumptions indicate
      deviations from both. Other factors potentially causing problems for
      retrospective dosimetry, such as inter-individual variations in background and
      induction patterns, are discussed. Finally, a brief analysis of the statistical
      power of dosimetry studies shows that establishing low doses (approximately 0.25
      Gy) with good precision requires a great effort, which is probably unrealistic
      for individual dose estimates in epidemiological studies.

PMID- 9001583
TI  - Micronuclei: a biological indicator of radiation damage.

PMID- 9001582
TI  - Nomenclature systems for FISH-painted chromosome aberrations.

PMID- 9001584
TI  - Radiation induced apoptosis.
AB  - The response to ionising radiation, in terms of level of cell killing, depends on
      a number of factors that may be grouped into those that are genetically
      controlled, radiation quality and dosage, and environmental factors. There is a
      range of genetically controlled cellular properties such as stage of
      differentiation, mutations in specific genes (such as p53 and bcl-2) and stage of
      transformation that will determine the ability of the target cell to enter
      apoptosis. The so-called normal cells, are usually more radiosensitive and the
      majority of the cell population will enter into an apoptotic death. However, in
      response to high doses of ionising radiation and complex DNA damage as produced
      by high-LET radiation, an increased fraction of these cells will die by necrosis.
      There are several examples of environmental factors with relevance for the
      combined action of radiation and xenobiotics on carcinogenesis and in tumour
      therapy. In the case of normal cells, agents such as growth factors and tumour
      promoters, may decrease radiosensitivity. For certain type of tumour cells,
      radiation sensitivity can be increased in the presence of agents such as
      hormones, and the cells may die an apoptotic death. Removal of heavily
      compromised cells is essential to prevent a potential spreading of mutated
      clones. However, if apoptosis is inhibited (e.g., by tumour promoter), an
      increased fraction of damaged cells carrying genotoxic lesions may survive. This
      would significantly increase the risk of proliferation of precancerous cells. As
      discussed above, it is probably incorrect to make predictions about relative
      radiosensitivity based solely on mode of death. Intrinsic characteristics
      deriving from the cell type of origin of a line may be more important in
      determining radiosensitivity. The rapidly increasing knowledge about the process
      of radiation induced apoptosis has opened new frontiers in radiation biology,
      genetic toxicology, and cancer therapy and strongly motivates further research in
      this field.

PMID- 9001585
TI  - Comparison of nicotinic receptor binding and biotransformation of coniine in the
      rat and chick.
AB  - Coniine, an alkaloid from Conium maculatum (poison hemlock), is a known teratogen
      in many domestic species with maternal ingestion resulting in arthrogryposis of
      the offspring. We have previously shown that rats are not susceptible and rabbits
      only weakly susceptible to coniine-induced arthrogryposis. However, the chick
      embryo does provide a reproducible laboratory animal model of coniine-induced
      teratogenesis. The reason for this cross-species variation is unknown. The
      purpose of this study was to evaluate coniine binding to nicotinic receptors and
      to measure coniine metabolism in vitro between susceptible and non-susceptible
      species. Using the chick model, neither the peripheral nicotinic receptor
      antagonist d-tubocurarine chloride nor the central nicotinic receptor antagonist
      trimethaphan camsylate blocked the teratogenesis or lethality of 1.5% coniine (50
      microliters/egg). Trimethaphan camsylate enhanced coniine-induced lethality in a
      dose-dependent manner. Neither nicotinic receptor blocker prevented nicotine
      sulfate-induced malformations but d-tubocurarine chloride did block lethality in
      a dose-dependent manner. Competition by coniine for [125I]-alpha-bungarotoxin to
      nicotinic receptors isolated from adult rat diaphragm and chick thigh muscle and
      competition by coniine for [3H]-cytisine to receptors from rat and chick brain
      were used to assess coniine binding to nicotinic receptors. The IC50 for coniine
      in rat diaphragm was 314 microM while that for chick leg muscle was 70 microM.
      For neuronal nicotinic receptors, the IC50s of coniine for maternal rat brain,
      fetal rat brain, and chick brain were 1100 microM, 820 microM, and 270 microM,
      respectively. There were no differences in coniine biotransformation in vitro by
      microsomes from rat or chick livers. Differences in apparent affinity of coniine
      for nicotinic receptors or differences in the quantity of the nicotinic receptor
      between the rat and chick may explain, in part, the differences in susceptibility
      of coniine-induced teratogenesis between these two species.

PMID- 9001586
TI  - Pre-implantation embryonic loss induced by tributyltin chloride in rats.
AB  - The effect of tributyltin chloride (TBTCl) administered during early pregnancy on
      pregnancy maintenance was evaluated in rats. Inseminated females were orally
      administered TBTCl at a dose of 0, 8.1, 12.2 or 16.3 mg/kg on day 0 through day 7
      of pregnancy. Females were sacrificed on day 20 of pregnancy and pregnancy
      outcome was determined. Pregnancy failure, which was evidenced by absence of
      implantation sites, was found in 0 of the 10, in 2 of the 11, in 10 of the 14 and
      in 10 of the 13 females at 0, 8.1, 12.2 and 16.3 mg/kg, respectively. The rate of
      pregnancy failure was significantly higher in the 12.2 and 16.3 mg/kg groups than
      that in the control group. In females with successful pregnancy, the numbers of
      corpora lutea, implantations and post-implantation loss per litter were
      comparable across all groups. No increase in the incidence of malformed fetuses
      was found in any TBTCl-treated groups. Thus it appears that TBTCl causes
      pregnancy failure after administration during very early pregnancy.

PMID- 9001587
TI  - Effects of polychlorinated biphenyls on dopamine release from PC12 cells.
AB  - In PC12 cells, Aroclor 1254 produced a concentration-dependent decrease in basal
      and K(+)-evoked dopamine (DA) release, and cellular DA levels. Aroclor 1254 did
      not alter the fraction of cellular DA released, suggesting that the decreased
      release of DA was solely due to decreased cellular levels of DA, and not to
      decreased packaging of DA or inhibition of neurotransmitter release. The coplanar
      congener 3,3',4,4',5-pentachlorobiphenyl decreased cellular DA levels and release
      of DA at levels that produced cytotoxicity. Absent of any apparent cytotoxicity,
      the ortho-substituted PCB congeners 2,2',5,5'-tetrachlorobiphenyl, 2,2',3,3',4,4'
      hexachlorobiphenyl, 2,3',4,4',5-pentachlorobiphenyl, and 2,2',4,4',5,5'
      hexachlorobiphenyl were effective in decreasing the amount of DA released from
      PC12 cells. These results suggest that ortho-chlorinated PCBs can cause decreased
      K(+)-evoked DA release through non-Ah receptor-mediated mechanisms. Furthermore,
      the PCB-mediated decrease in DA release was not due to impairment of DA packaging
      or release, but only due to decreased cellular DA levels.

PMID- 9001588
TI  - Effect of sub-chronic cocaine and lidocaine exposure on the lymphoid tissues in
      neonatal rats.
AB  - Illicit cocaine varies in purity and is often adulterated with local anesthetics
      such as lidocaine. Chronic cocaine exposure is associated with immunological
      modulation in humans and animal models. The effect of sub-chronic oral exposure
      to cocaine (COC) and lidocaine (LIDO) alone and in combination on the lymphoid
      organs was assessed in neonatal rats. Lewis rat pups were orally administered
      saline (SAL), COC, LIDO or both drugs in combination, 20 mg/kg each, from birth
      to day 21. Statistically significant (P < 0.05) decreases in lymphocyte and total
      leukocyte levels as well as decreases in spleen weight were observed in pups
      treated with COC alone. LIDO alone did not affect these parameters in comparison
      to SAL treated controls. Rats receiving COC and LIDO did not display a
      significant reduction in spleen weight or in the blood cell populations studied.
      However, rats treated with COC and LIDO in combination had significantly
      decreased serum immunoglobulin M (IgM) concentration. Quantitative plasma and
      tissue analyses ascertained the concentrations and tissue disposition of each
      drug following oral administration. The results suggest that the effect of COC on
      the lymphoid tissues and white blood cell parameters is modified in the presence
      of LIDO in the developing rat.

PMID- 9001589
TI  - Chromium induced teratogenicity in female rat.
AB  - Exposure to chromium (VI) (250, 500 and 750 ppm as potassium dichromate) via
      drinking water pregestationally in rats revealed embryo- and fetotoxic effects in
      the form of a significant reduction in the number of implantations and number of
      fetuses. An increase in the number of resorptions, pre-implantation and post
      implantation loss in chromium (VI)-treated mothers was also observed. No
      significant visceral abnormality was found. A significant increase in sub-dermal
      hemorrhagic patches on thoracic and abdominal areas was found. Skeletal
      abnormality in the form of reduced ossification in parietal, interparietal and
      caudal bones was found in the fetuses of chromium (VI)-treated mothers. Chromium
      levels in blood, placenta and fetuses were found to be significantly increased in
      the 500 ppm and 750 ppm dosed groups. The duration of estrus cycle was
      significantly altered after chromium (VI) exposure. This study suggests that
      chromium exposure in rat causes a lower degree of toxicity than in mice as
      observed in our earlier studies.

PMID- 9001590
TI  - Effects of 4-hydroxynonenal and N-acetyl-L-cysteine on Myc-induced apoptosis.
AB  - Apoptosis has been described as programmed active cell death. Overexpression of
      the c-Myc gene has been shown to induce apoptosis in Rat1A/Myc-ER cells when
      combined with a growth blocking agent. In the present study, we tested whether 4
      Hydroxynonenal (HNE) or N-acetyl-L-cysteine (LNAC) affect apoptotic death in
      serum deprived Rat1A/Myc-ER cells caused by the c-Myc protein. The incidence of
      apoptosis in growth arrested cells was confirmed photographically and by ladder
      pattern formation seen on agarose gel electrophoresis. To study the effect of HNE
      and LNAC, the cells were cultured in 0.5% serum and treated with various
      concentrations of HNE and LNAC, c-Myc was then activated by addition of 2 microM
      beta-estradiol. Two separate parameters were used to determine the rate of cell
      death. In the first, the amount of DNA isolated from dying cells was compared by
      UV absorption. As the second parameter, the cell numbers were determined by
      counting. Our results showed that 1 microM of HNE has no effect on apoptotic cell
      death. However, 10 microM HNE decreased the amount of DNA isolated while
      increasing the cell count 14% relative to cells treated only with beta-estradiol.
      In addition, we found that various concentrations of the antioxidant LNAC does
      not protect cells from c-Myc induced death. However, it supports cell survival in
      0.5% serum and causes an increase in cell number.

PMID- 9001592
TI  - Mechanism for mouse strain differences in the protective effect of Sudan III
      against the in vivo genotoxicity of 7,12-dimethylbenz[a]anthracene.
AB  - The effect of Sudan III-pretreatment on the in vivo genotoxicity of 7,12
      dimethylbenz[a]anthracene (DMBA) was investigated using C57BL/6 (B6) and DBA/2
      (D2) mice. A significant increase in the frequency of micronucleated
      reticulocytes was observed in both strains of mice treated with DMBA. The
      increase was significantly reduced in B6 but not D2 mice by Sudan III
      pretreatment. However, enhancement of metabolic activation was found in the Ames
      assay in the hepatic post-mitochondrial supernatant fraction (S9) from Sudan III
      treated animals. It was greater with S9 from B6 than S9 from the D2 group. When
      the assay was performed in the presence of glutathione, this enhancement was
      significantly reduced. Sudan III induced some drug metabolizing enzymes, mainly
      CYP1A and glutathione S-transferase was also induced. The induction of CYP1A was
      more effective in B6 than D2 mice. These results support our hypothesis that the
      simultaneous induction of Phase I and II drug metabolizing enzymes is the
      mechanism for the chemoprevention by Sudan III and suggest that strong induction
      of CYP1A might be essential for a protective effect.

PMID- 9001591
TI  - Formation of GSH-derivatives as a pathway for inactive intermediates in
      vinylidene chloride-treated rats.
AB  - The two conjugates, S-[N-(2-hydroxyethyl)carbamoylmethyl]glutathione (GSAAE), and
      its corresponding mercapturic derivative N-acetyl-S-[N-(2
      hydroxyethyl)carbamoylmethyl]cysteine (NCySAAE) were administered to fasted
      Sprague-Dawley rats as putative metabolites of vinylidene chloride (VDC).
      Methylthioacetylaminoethanol (MAAE) was identified in the urine of GSAAE- or
      NCySAAE-treated rats (0.5-2.0 mmol/kg, i.p.), as well as in the urine of VDC
      treated rats (0.5-2.0 mmol/kg, p.o.). The effects of VDC, GSAAE and NCySAAE on
      the kidney and liver were also examined using aspartate aminotransferase (ASAT).
      N-acetyl-beta-D-glucosaminidase (NAG) and beta 2-microglobulin (beta 2-m) as
      urinary parameters of nephrotoxicity, and glutamate dehydrogenase (GLDH),
      sorbitol dehydrogenase (SDH) and alanine aminotransferase (ALAT) as serum
      parameters of hepatotoxicity. Unlike treatment with VDC, treatment with both
      GSAAE and NCySAAE failed to cause kidney and liver toxicity. The results support
      the hypothesis that MAAE originates from the formation of GSAAE and further
      metabolization to NCySAAE, and that MAAE excretion does not reveal a pathway of
      reactive intermediates.

PMID- 9001593
TI  - An automatable microassay for phenyl valerate esterase activities sensitive to
      organophosphorus compounds.
AB  - An automatable microassay method developed for phenyl valerate esterase (PVase)
      activity has been applied to determine the following activities in the soluble
      fraction of hen sciatic nerve: activity A (total PVase activity), activity B
      (paraoxon-resistant PVase activity), activity C (PVase activity resistant to 40
      microM paraoxon and 250 microM mipafox) and neuropathy target esterase (NTE)
      activity (resistant to 40 microM paraoxon but sensitive to 250 microM mipafox),
      operationally defined as activity (B-C). This microassay is based on the
      technique described by Barril et al. (Toxicology. 1988. 49:107-114). The
      Automated Biomek 1000 Station was used, which guarantees both inter- and intra
      assay reproducibility of the results, and shortens the total assay time. The
      technical problems involved when processing many samples were thus resolved and
      with same regards it can also apply manually and using a microplate reader. In
      the case of activity A, the sensitivity of the method allowed the detection of
      activity in 1 microgram of protein (0.15 mg fresh sciatic nerve tissue), and the
      response was linear for different concentrations of 0.15-1.7 mg fresh tissue. For
      B, C and NTE, sensitivity corresponded to 10 micrograms of protein (1.5 mg fresh
      tissue in the microassay), with a linear response in the range of 1.5-17 mg fresh
      tissue. The response was linear versus the time of enzyme-substrate reaction (30
      150 min). As tissue concentration increased, the response became nonlinear at
      shorter time. The procedure may be used to measure other enzymatic activities
      that yield phenols and chlorophenols as reaction products.

PMID- 9001594
TI  - Effect of vitamin C supplementation on hepatic cytochrome P450 mixed-function
      oxidase activity in streptozotocin-diabetic rats.
AB  - The effect of vitamin C supplementation on hepatic cytochrome P450 expression was
      investigated in streptozotocin (STZ) diabetic male Wistar Albino rats. STZ
      treated rats displayed the usual characteristics of diabetes including;
      hyperphagia, polydipsia, decreased body weight gain and also the increased
      expression and activity of hepatic CYP1A, 2B, 2E and 4A proteins. Vitamin C
      administration in drinking water (2% w/v) was associated with significant
      decreases in the levels of hyperglycaemia (P < 0.05), glycosylated haemoglobin (P
      < 0.05), hyperlipidaemia (P < 0.001), and hyperketonaemia (P < 0.001) associated
      with STZ-diabetes. Vitamin C-treatment selectively reduced the activity and
      expression of CYP2E proteins (P < 0.001). These effects on CYP2E expression may
      be mediated by the reduced levels of circulating ketone bodies, however, a direct
      effect on CYP2E expression in diabetes cannot be discounted.

PMID- 9001596
TI  - A parallel broadband real-time system for electrical impedance tomography.
AB  - This paper deals with the design, implementation and performance of TIE-4sys, an
      electrical impedance tomograph. This instrument is a parallel broad-band real
      time system. It measures impedance using an array of 16 electrodes and
      reconstructs the images using a weighted back-projection technique. The objective
      of this development is to enable multifrequency EIT clinical studies to be
      undertaken. The system is capable of acquiring 25 frames/s and makes
      multifrequency cardiac-gated images. The frequency range is from 10 kHz to 250
      kHz and the signal to noise ratio for the real component is better than 60 dB.

PMID- 9001595
TI  - Hepatic clearance and retention of aluminium: studies in the isolated perfused
      rat liver.
AB  - Aluminium (Al) exposure can result in Al accumulation in the liver and this metal
      can be toxic to the hepatic tissue at high concentrations. In the present study
      the model of the isolated perfused rat liver was used to investigate the hepatic
      handling of Al. Livers from male Wistar rats were perfused in a recirculating
      system for 240 min. The liver function remained unchanged at perfusate
      concentrations of Al ranging from 4.9 to 1530.0 micrograms/l. At higher Al levels
      of 6535.3-16694.9 micrograms/l signs of toxicity towards isolated perfused livers
      were observed as indicated by an increased release of the enzymes AST and ALT
      into the perfusate, a pronounced reduction of bile flow rate and a 50%
      suppression of oxygen consumption. The hepatic Al clearance was low and decreased
      with increasing concentrations of Al in the perfusate from 4.3 +/- 0.6
      microliters/min per g liver at a nominal Al concentration of 9.1 micrograms/l in
      control perfusate to 0.04 +/- 0.02 microliter/min per g liver at the highest
      concentration group. There was almost a linear dose dependent retention of Al in
      the liver with 4.9-635.7 micrograms Al/l perfusate while at higher concentrations
      Al levels in this organ increased disproportionally. It is concluded that by
      using the isolated perfused rat changes of liver functions occur only at very
      high Al concentrations in the perfusate and that only negligible amounts of Al
      are eliminated by the liver.

PMID- 9001597
TI  - A multifrequency serial EIT system.
AB  - A multifrequency (1 kHz-1 MHz) serial electrical impedance tomography (EIT)
      system has been developed. It is based on 16 active electrodes and can be
      extended up to 32. Each active electrode can be programmed for current driving
      and for measuring either the injected current or the voltage difference between
      adjacent electrodes, and includes calibration facilities. Real and imaginary
      parts of the impedance are obtained by applying a parametric identification
      method (extended Prony), but other techniques are easily adaptable. Image
      reconstruction is carried out using the Sheffield filtered back-projection
      algorithm. Characteristic frequency images are under development and should be of
      great interest to distinguish between normal and tumorous tissues.

PMID- 9001598
TI  - An electrical impedance tomography microscope.
AB  - A circular array of 16 electrodes has been constructed for use as an electrical
      impedance tomography (EIT) microscope. The electrodes were made from 60 microns
      diameter gold wires anchored to a printed circuit board. The internal diameter of
      the array was 0.9 mm giving a theoretical spatial resolution of about 100
      microns. For EIT imaging, the array was connected to an imaging system operating
      at 82 kHz. Static images of conducting and insulating filaments (cooper wire and
      human hair) in saline solution were obtained as well as dynamic imaging sequences
      of glass microspheres migrating through the array. The interelectrode impedance
      was typically 5 k omega and the transimpedances ranged from 14 to 210 omega.

PMID- 9001599
TI  - Fast EIT data acquisition system with active electrodes and its application to
      cardiac imaging.
AB  - A wide-band high-speed data acquisition system for electrical impedance
      tomography (EIT) is described. 32 active electrodes are used in the system, half
      of them as receive electrodes and the other half as drive electrodes. A buffer is
      mounted on the back of each receive electrode and a current source on each drive
      electrode. A multielectrode system with active electrodes was built to make it
      convenient to attach all the electrodes on the human thorax. The system is
      suitable for both dynamic imaging and multifrequency electrical impedance
      tomography (MFEIT). Its operating frequency can be chosen between 24 kHz and 400
      kHz. Current is injected sequentially into 16 adjacent current electrode pairs
      and the 16 voltages between adjacent receive electrodes are measured for each
      current injection. ECG is collected to determine the relationship between the
      reconstructed images and cardiac activity. The collection of one frame of data is
      completed within 25 ms. The system has been successfully used for imaging the
      variation of conductivity distribution of the human thorax. The beat-by-beat
      cardiac-related change of conductivity distribution has been imaged by our
      system. The quasi-periodic variation of the impedance distribution can be seen
      from the image sequence with breath-holding.

PMID- 9001600
TI  - EIT data noise evaluation in the clinical environment.
AB  - In the clinical environment the reliable interpretation of EIT images depends on
      the quality of the data. In the electrically noisy hospital environment the
      system performance needs to be assessed for each clinical investigation. From the
      model of noise presented, a figure of merit for comparisons of system performance
      with a known standard, or with previous studies, can be generated. The method
      depends on calculating the variances of the differences in reciprocity
      measurements as a function of the distance between the current drive electrodes
      and the receive voltage electrodes. These measurements fit the noise model, with
      minimal interference from physiological variability, and permit a figure of merit
      to be calculated which is a representation of the noise at the point to the
      system. Typical figures of merit are 7.36 +/- 0.03 microV for a test card and
      10.50 +/- 16 microV for subject data.

PMID- 9001601
TI  - Broadband quasi-differential multifrequency electrical impedance imaging system.
AB  - Dynamic and multifrequency imaging methods have been demonstrated both
      theoretically and experimentally. Multifrequency methods are able to produce
      images of static structures inside the measured object. Data collection systems,
      however, are affected by errors due to their non-ideal frequency behaviour. If
      the frequencies used in the measurement were close enough, the system would
      behave in almost the same way. In this case, however, the impedance change
      displayed by biological tissues is small, so the situation is similar to dynamic
      imaging. We call this method the quasi-differential imaging method. We have
      designed and built an instrument able to apply signals from 1 kHz to 1 MHz, with
      frequency increments of 10 Hz. Patient interface circuits and demodulators were
      designed to display a flat response in the full frequency range of operation.
      Signals are digitized with 16 bit resolution and sent to the host computer using
      a high-speed serial interface. This allows a maximum measurement speed of about 8
      images/s. All the system parts were full characterized out of the system and the
      results of these measurements are given as an indication of the limits of its use
      as a quasi-static imaging or quasi-differential imaging data collection system.

PMID- 9001602
TI  - Improvement of the positional accuracy of EIT images of the head using a Lagrange
      multiplier reconstruction algorithm with diametric excitation.
AB  - A novel algorithm for the reconstruction of dynamic images using diametric
      excitation has been developed. The algorithm is specifically designed to image
      impedance changes in the brain using boundary data obtained from scalp electrodes
      by incorporating a priori information. The a priori information is obtain by
      solving the forward problem using a finite-element model (FEM) which includes the
      discontinuity of the skull resistivity. The advantages with this new approach are
      that the sensitivity and accuracy of the location of the impedance changes are
      improved compared to methods based on adjacent excitation.

PMID- 9001603
TI  - An interleaved drive electrical impedance tomography image reconstruction
      algorithm.
AB  - In this study, a reconstruction algorithm for a 16-electrode interleaved-drive
      electrical impedance tomography (EIT) system is developed, based on inversion of
      an analytically calculated sensitivity matrix. The sensitivity matrix is
      calculated using Geselowitz's lead-sensitivity theorem. Eight interleaved
      electrodes out of 16 (equally spaced) electrodes are designated as current
      injection electrodes and the remaining eight electrodes are designated as
      measurement electrodes. The sensitivity matrix is singular, therefore singular
      value decomposition (SVD) of the sensitivity matrix, followed by pseudoinversion
      with and without truncation-is used to reconstruct images. The algorithm is a
      single-pass algorithm. Data from a saline filled tank and in vivo data during
      respiration and the cardiac cycle, acquired by using a Sheffield multifrequency
      system, are used to reconstruct images. The effect of different truncation levels
      on the reconstructed images is investigated.

PMID- 9001604
TI  - Penalty methods for the inverse problem in EIT.
AB  - The conductivity profiles arising in medical applications of electrical impedance
      tomography (EIT) are often of 'blocky' structure, i.e. they are relatively
      constant inside an organ and are rapidly varying at its boundary. Standard
      regularization methods for the inverse problem tend to blur these sharply defined
      edges. A penalty method is proposed which is especially designed for a better
      reconstruction of discontinuous conductivity profiles.

PMID- 9001605
TI  - Three-dimensional image reconstruction for electrical impedance tomography.
AB  - Very little work has been conducted on three-dimensional aspects of electrical
      impedance tomography (EIT), partly due to the increased computational complexity
      over the two-dimensional aspects of EIT. Nevertheless, extending EIT to three
      dimensional data acquisition and image reconstruction may afford significant
      advantages such as an increase in the size of the independent data set and
      improved spatial resolution. However, considerable challenges are associated with
      the software aspects of three-dimensional EIT systems due to the requirement for
      accurate three-dimensional forward problem modelling and the derivation of three
      dimensional image reconstruction algorithms. This paper outlines the work
      performed to date to derive a three-dimensional image reconstruction algorithm
      for EIT based on the inversion of the sensitivity matrix approach for a finite
      right circular cylinder. A comparison in terms of the singular-value spectra and
      the singular vectors between the sensitivity matrices for a three-dimensional
      cylinder and a two-dimensional disc has been performed. This comparison shows
      that the three-dimensional image reconstruction algorithm recruits more central
      information at lower condition numbers than the two-dimensional image
      reconstruction algorithm.

PMID- 9001606
TI  - Optimal filtering of EIT data in spectral expansion analysis.
AB  - The signal-to-noise rations for some EIT measurements are very low, and for in
      vivo EIT measurements these are dependent on the electrode positioning and the
      distance from the current drive. The effect of removing noisy measurements to
      produce higher-fidelity images was investigated for the case of gastric emptying
      data. A consequence of this filtering was the reduction in the size of the
      sensitivity matrix and its subsequent singular-value decomposition. Several
      different filters were tested and for each of these spectral expansion
      regularization filter was optimized using a chi 2 test. Filtering out the
      measurement made by the spinal electrode, where the spinal bone barrier lies
      directly in the current path to the stomach, produced improved images by reducing
      the artefact content in the spinal sector of the conductivity map. For stomach
      imaging little useful information is produced by the spinal electrode, and the
      benefits of filtering dominate. However artefact images may be generated. In
      contrast consistent small improvements were produced by filtering out some of the
      weakest signals.

PMID- 9001607
TI  - Some boundary problems in electrical impedance tomography.
AB  - Accurate mathematical modelling is important in the development of iterative
      image reconstruction algorithms for electrical impedance tomography (EIT). In
      such schemes the forward problem of calculating the electric potential from
      Neumann boundary data is solved many times. One aspect of this problem which has
      received some attention is the mathematical modelling of the electrodes used in
      the technique. In this paper we describe an integral equation formulation of a
      boundary value problem associated with this tissue and we indicate some of the
      ways in which this formulation can be used to obtain numerical and analytic
      results.

PMID- 9001608
TI  - In vitro multifrequency electrical impedance measurements and modelling of the
      cervix in late pregnancy.
AB  - Idiopathic preterm labour is the greatest single perinatal problem occurring in
      an unpredictable 6-8% of all pregnancies and accounting for 75% of all perinatal
      deaths. Preterm cervical softening is used clinically as an important indicator
      of cervical dysfunction but the subjective nature of present clinical assessment
      methods prevents reliable prediction of preterm labour. This paper reports the
      finding of a pilot investigation concerned with obtaining quantitative
      measurements of the in vitro electrical impedance of the cervix using a four
      electrode multifrequency impedance measurement system. Impedance measurement
      obtained from six samples of cervical tissue taken from different subjects of
      caesarean section were fitted to the Cole equation and parameters derived to
      describe the ratio of extra- versus intracellular impedance and the
      characteristic frequency. Subjects at term display a lower extra- versus
      intracellular impedance ratio than the preterm subjects. This appears consistent
      with the expected increase in the hydration of the cervix approaching term and
      the resulting decrease in the extracellular impedance. Further studies are
      required to determine if multifrequency electrical impedance tomography could be
      used as a non-invasive screening test for preterm labour.

PMID- 9001609
TI  - Impedance spectra of tumour tissue in comparison with normal tissue; a possible
      clinical application for electrical impedance tomography.
AB  - Electrical characteristics of living tissues have been investigated for a long
      time in the search for further methods to complement the traditional
      investigations of pathology and physiology. Tumour tissue has been shown to
      exhibit a larger permittivity and conductivity than normal tissues. This might be
      associated with the fact that tumour cells have a higher water content and sodium
      concentration than normal cells, as well as different electrochemical properties
      of their cell membranes. To our knowledge only a few contributions on this
      subject have been published. This study describes an additional application on
      measurements of the complex impedance of tumour and normal tissues, in order to
      compare the impedance features of the two tissue types. The tissue sample is
      placed in a measuring cell in which the temperature is controlled. The measuring
      cell is connected to an impedance meter able to measure the complex impedance in
      terms of real and imaginary part curves for frequencies from 1.5 kHz to 700 kHz.
      The four-electrode principle is used with the current injected by the outer
      electrodes and the voltage difference measured between the inner electrodes. The
      current can be altered up to 1 mA. The instrument can be calibrated with known
      resistance and capacitance networks connected to the input of the instrument in
      order to minimize the measurement errors. The calibration routine uses a
      polynomial adaptation and can be applied interactively. Measurements performed by
      the instrument show promising results. Preliminary results show that this method
      can be extended to a new application for detection of tumour tissue by electrical
      impedance tomography (EIT).

PMID- 9001611
TI  - Electrode-skin impedance from a dielectric viewpoint.
AB  - It is well established that the frequency variation of the complex electrode-skin
      impedance (ESI) Z is given by Z = K(i omega)-n, where n has a typical value of
      about 0.8. It is not easy to find a physical reason for this behaviour. However,
      many materials exhibit Cole-Davidson (CD) behaviour, so that in the high
      frequency (hf) region their impedance has a characteristic which is almost
      indistinguishable from that of the ESI. It is therefore possible that the ESI
      exhibits a behaviour given by the CD equation or one of its variants, but that
      this has not been detected because experimental measurements have not extended to
      sufficiently low frequencies. Whatever the ESI behaviour may be at low
      frequencies, there are theoretical reasons which show that Z cannot obey the
      above equation indefinitely as the frequency is reduced. If the deviation from it
      at low frequencies were found to be consistent with CD behaviour, then a physical
      explanation in terms of protonic fluctuations, which has previously been put
      forward to explain CD behaviour, would be available as a possible explanation of
      ESI behaviour over the whole frequency range. It is shown that any such deviation
      would be more likely to be detected if the variation of complex capacitance with
      frequency, rather than of impedance with frequency, were to be plotted.

PMID- 9001610
TI  - EITS changes following oleic acid induced lung water.
AB  - We present the results of using electrical impedance tomographic spectroscopy
      (EITS) to follow the changes in lung water induced by oleic acid. Measurements
      were made on three goats before and after the injection of oleic acid. In
      addition to the EITs measurements, lung water was also measured using a double
      indicator technique. Large falls in lung electrical impedance were seen as a
      result of the increase in lung water but the size of the fall was a function of
      the frequency at which the measurements were made. These changes have been
      modelled using the Cole equation. Four-electrode measurements were also made on
      two extracted porcine lungs and Cole equation modelling carried out following the
      introduction of saline into the lungs. Results were similar in the two sets of
      animal experiments.

PMID- 9001612
TI  - Can electrical impedance tomography be used to detect gastro-oesophageal reflux?
AB  - A number of experiments have been carried out to investigate the feasibility of
      using electrical impedance tomography as an alternative method for identifying
      gastro-oesophageal reflux. Five subjects have been studied using simultaneous EIT
      and intraoesophageal pH measurements. A refluxogenic meal was given during the
      course of the recording to induce reflux in the subjects. Results show that there
      is some change in conductivity in the stomach region during some of the reflux
      episodes, but EIT is not able to detect all of the pH changes associated with the
      reflux. Other large conductivity changes, relating to gastric motility can be
      detected at times when no reflux is occurring.

PMID- 9001613
TI  - Gravity-dependent phenomena in lung ventilation determined by functional EIT.
AB  - Gravity exerts an effect on the distribution of intrapulmonary ventilation. A
      study on the detection of gravity-dependent inhomogeneity of ventilation by a
      functional EIT technique is presented. The study was performed on five human
      subjects, whose ventilation distribution was modified by changes in body
      position. The subjects were studied during spontaneous tidal breathing. The
      qualitative and quantitative analysis of the functional EIT images revealed that
      the ventilation is higher in the dependent lung regions when compared with the
      non-dependent ones. These EIT findings correspond to current knowledge of the
      physiological behaviour of the lungs as derived from the radioactive-gas methods
      and raise the possibility of applying the less complicated functional EIT in
      future studies on ventilation distribution in the lungs. This may be of major
      interest in the monitoring of intensive care patients with severe pulmonary
      disorders.

PMID- 9001614
TI  - Local mechanics of the lung tissue determined by functional EIT.
AB  - A new functional EIT (f-EIT) evaluation technique providing information on the
      local dynamic behaviour of the lung is presented. Out of a series of single EIT
      thoracic images local time courses of the impedance change are extracted. To
      detect regional differences in the dynamic behaviour of the lung tissue the local
      time courses at different locations are related to the average time course of the
      impedance change over the whole thoracic cross section. The time shifts between
      this reference signal and the signals from separate positions are calculated from
      the phase information of the complex cross spectra and evaluated in terms of the
      local phase angle. The computed phaseshifts are imaged over the cross section
      creating an 'f-EIT phase image' characterizing the local dynamic properties. To
      relate the observed differences to the proper lung location the resulting images
      are presented as a combination of the f-EIT ventilation images, which represent
      the local amplitude of ventilation and the f-EIT phase images. The new imaging
      technique was tested in spontaneously breathing humans. Alterations to pulmonary
      dynamics were induced by changing the body posture of the subjects. The f-EIT
      phase imaging procedure was shown to identify lung regions with different
      dynamics and it is expected that this technique will also distinguish
      pathologically determined alterations.

PMID- 9001615
TI  - Some practical biological phantoms for calibrating multifrequency electrical
      impedance tomography.
AB  - Three groups of materials have been assessed with a Hewlett-Packard 4284A
      impedance analyser and Sheffield Mark 1 electrical impedance tomography (EIT)
      system for suitability for calibration of multifrequency EIT systems. They were
      required to be easy to use, stable over several hours, and have complex impedance
      similar to biological tissue. The groups were: (i) inorganic materials including
      barium titanate, polystyrene microspheres and fumed silica, all in aqueous
      suspension; these had phase angles below 1 degrees and so were unsuitable. (ii)
      Cucumber in KCl solution. Cucumber cortex had a phase angle of 40 degrees at a
      centre frequency of 50 kHz. Contrast between the cucumber and bathing solution
      could be selected by varying the KCl concentration. (iii) Polyurethane sponge
      immersed in packed red cells. The phase angle of packed cells was about 25
      degrees at 1 MHz. Sponge resistivities and permittivities when immersed in packed
      cells were 5-20% higher than the bathing solution itself, for densities of 2-6.2%
      w/v. Both the biological materials appear suitable for the intended purpose;
      system (iii) is inherently more stable, and has capacitance in both bathing
      medium and test object. If an initial accuracy of greater than about +/- 15% is
      required, direct measurement with an impedance analyser is recommended prior to
      imaging studies.

PMID- 9001616
TI  - Imaging of physiologically evoked responses by electrical impedance tomography
      with cortical electrodes in the anaesthetized rabbit.
AB  - The purpose of this study was to determine if electrical impedance tomography
      (EIT) could be used to image impedance changes of several per cent over tens of
      seconds, known to occur during evoked activity of the cerebral cortex. A ring of
      16 electrodes was placed on the exposed superior surface of the brain of
      anaesthetized rabbits. EIT images were acquired every 15 s using a Sheffield Mark
      1 EIT system. During periods of 2.5-3 min of intense photic stimulation of both
      eyes or electrical stimulation of a forepaw, reproducible impedance decreases of
      4.5 +/- 2.7% and 2.7 +/- 2.4% (mean +/- SD) respectively occurred in appropriate
      cortical areas, with a time course similar to the period of stimulation. They
      were accompanied by adjacent smaller impedance increases. The decreases are
      probably due to increased blood flow and temperature; the cause of the adjacent
      increases may be a shadowing artefact of the reconstruction algorithm or due to
      physiological shrinkage of the extracellular space. This demonstrated, for the
      first time, that such small changes may be imaged under optimal conditions. These
      results are encouraging to the prospect that EIT may eventually be suitable for
      imaging evoked responses or epilepsy in human subjects.

PMID- 9001618
TI  - Subsurface electrical impedance imaging: measurement strategy, image
      reconstruction and in vivo results.
AB  - In conventional cross-sectional electrical impedance tomography, most of the
      spatial information is concentrated at the periphery of the image, close to the
      measurement electrodes. Increasing the number of electrodes tends not to increase
      the poor resolution at the centre of the cross-sectional image due to the physics
      of three-dimensional current flow. In this work an alternative approach. INSEIT
      (imaging near the surface by electrical impedance tomography), is explored in
      which the image plane lies at a selected depth in the object parallel to a
      surface electrode array. This approach has been investigated using a prototype
      data measurement system. The preliminary in vivo results include subsurface
      images of respiration, the gastro-intestinal tract and limb blood flow.

PMID- 9001617
TI  - Electrical impedance tomography of the eye: in vitro measurements of the cornea
      and the lens.
AB  - This study was designed to perform multifrequency impedance measurements on the
      pig's eye. On one hand, impedance of the ocular tissues was measured from 10 kHz
      to 10 MHz. The aqueous and vitreous humours and the cornea showed no relaxation
      in this range of frequencies, whereas the lens and its parts (the cortex and the
      nucleus) did. On the other hand, multifrequency EIT and dynamic imaging were
      performed on the lens and on the whole eye. Data and images obtained after
      thermal and chemical injuries are presented and discussed.

PMID- 9001619
TI  - Reproducibility of electrical impedance tomographic spectroscopy (EITS)
      parametric images of neonatal lungs.
AB  - The reproducibility of electrical impedance tomographic spectroscopy (EITS)
      images of neonatal lungs have been investigated in 11 clinically stable babies.
      We have used the Sheffield Mark IIIa EITS system. An average inspiration frame
      was generated from the data frames associated with maximum inspiration. Frequency
      images were reconstructed from these frames. The frequency images were analysed
      to locate the pixel with the maximum change in the right lung field. The change
      was defined as the 614 kHz measurement relative to 9.6 kHz. A 3 x 3 pixel region
      of interest was centred at this point. The changes in impedance with frequency
      for this region of interest show good overall reproducibility between electrode
      applications for eight frequencies (95% limits of agreement +/- 28%). This
      reproducibility is improved (95% limits of agreement +/- 13%) by omitting the
      highest frequency (1.2 MHz) which is most subject to system noise. The parameters
      for the Cole model derived from data with the highest frequency omitted are less
      reproducible between electrode applications (95% limits of agreement, R/S +/-
      0.83, fc +/- 81.6, RC +/- 0.52, SC +/- 0.39). We suspect that the parametric
      model used may have an effect on this. The signals recorded at the highest
      frequency (1.2 MHz) are a major source of variability. The reproducibility
      results are improved by omitting this frequency from the analysis.

PMID- 9001620
TI  - Cardiac-related changes in lung resistivity as a function of frequency and
      location obtained from EITS images.
AB  - ECG-gated electrical impedance tomographic spectroscopy (EITS) measurements of
      the lungs were taken on seven normal subjects in the frequency range 9.6 kHz to
      614.4 kHz. The results show that in late systole the resistivity p' relative to
      the R-wave (i.e. p' = 1 at the R-wave) decreases consistently within the lung. In
      addition there arises an increase in p' in early systole towards the periphery of
      the lung. Frequency behaviour of p' changes with location. At all times after the
      R-wave, in the centre of the lung p' is higher at higher frequency f whereas in
      the periphery it is lower at higher f. The principal decrease in p' can be
      explained by increasing pulmonary blood volume due to cardiac contraction. The
      early systolic increase is presumably due to venous return to the left atrium
      locally leading blood output from the right ventricle which is delayed by the
      windkessel effect. Based on a model taking extracapillary and capillary blood
      volume increase into account, the change in frequency behaviour of p' is
      explained by regional variations in extracapillary blood vessel size determining
      the relative contributions of extracapillary blood volume and capillary blood
      volume change to p' at a certain frequency.

PMID- 9001621
TI  - Modelling of cardiac-related changes in lung resistivity measured with EITS.
AB  - Resistivity data from 9.6 kHZ to 1.2 MHz were recorded from eight normal subjects
      using an electrical impedance tomographic spectroscopy (EITS) system and then
      averaged to a mean cardiac cycle using the ECG gating technique. The Cole-Cole
      model, that is, extracellular resistance R connected in parallel with
      intracellular resistance S and membrane capacitance C in series, with a
      distribution parameter a, was applied to model the frequency characteristics and
      to produce parametric images. During systole, SC and RC were found to decrease
      and FR increase. The changes in R/S were not consistent among the subjects. We
      estimated the peak changes in R, S and C to be -2.5%, -3.3% and -7.6%
      respectively. The results can be explained by considering the blood vessels as
      spheres of different sizes with blood inside them. The decrease in R during
      systole might be caused by the increased blood content in relatively large
      vessels, whereas that in S by the increased blood volume in relatively small
      vessels. The capacitance of blood is normally smaller than that of lung tissue,
      whereas FR blood is higher than that of lung tissue. Hence, as blood content
      increases, C should decrease and FR increase.

PMID- 9001622
TI  - Oral health policies. American Academy of Pediatric Dentistry.

PMID- 9001623
TI  - Guidelines. American Academy of Pediatric Dentistry.

PMID- 9001624
TI  - Quality assurance criteria. American Academy of Pediatric Dentistry.

PMID- 9001625
TI  - International Union of Crystallography XVII Congress and general assembly.
      Seattle, Washington, August 8-17, 1996. Abstracts.

PMID- 9001626
TI  - Proceedings of the joint meeting of the British Pharmacological Society and the
      Nordic Pharmacological Societies. University of Dundee. 11-13 September 1996.
      Abstracts.

PMID- 9001627
TI  - Gene Therapy of Cancer V. San Diego, California, November 14-16, 1996. Abstracts.

PMID- 9001628
TI  - XIIth Congress of the European Association of Urology. Paris, France, September 1
      4, 1996. Abstracts.

PMID- 9001629
TI  - Scientific meetings of the Italian Primatological Society, La Societe Francophone
      de Primatologie, and the Primate Society of Great Britain. 1995. Abstracts.

PMID- 9001630
TI  - 14th International Congress on Thrombosis. Montpellier, France, October 14-19,
      1996. Abstracts.

PMID- 9001631
TI  - Society for Gynecologic Investigation 43rd annual meeting. Philadelphia,
      Pennsylvania, March 20-23, 1996. Abstracts.

PMID- 9001632
TI  - Cumulative index volumes 1-19, 1978-1996.

PMID- 9001633
TI  - The 45th annual meeting of the Scandinavian Association for Thoracic Surgery and
      the 16th annual meeting of the Scandinavian Society for Extracorporeal
      Technology. Abstracts.

PMID- 9001634
TI  - Conference on Global Lung Health and the 1996 annual meeting of the International
      Union Against Tuberculosis and Lung Disease (IUATLD). Paris, France, 2-5 October
      1996. Abstracts.

PMID- 9001635
TI  - Exudative lesions of Reinke's space. An anatomopathological correlation.
AB  - Few anatomopathological criteria for distinguishing vocal nodules, polyps or
      REINKE's edema have been established in previously published studies. In order to
      study this issue, 163 samples (from 119 patients) were examined by an experienced
      anatomopathologist, without her prior knowledge of the macroscopic or microscopic
      diagnosis. In all the cases, the presence of exudative phenomena in REINKE's
      space proved to be the determining factors, with four outstanding stages of
      evolution: edema, fibrosis, deposits of fibrin and development of vascular
      ectasia. Although each of the three entities were seen to have their specific
      characteristics, a large number of lesions showed histological features which
      were not very specific, and were dominated by edema. Furthermore, the coexistence
      of different anatomopathological features makes each group heterogeneous. We
      propose a model which groups all the exudative lesions of REINKE's space by
      insisting, on the one hand, on the evolution of the anomalies and, on the other
      hand, the etiological factors (vocal misuse, tobacco, alcohol acute, vocal trauma
      ...) which determine the onset of either one or other lesion.

PMID- 9001636
TI  - The contribution of videostroboscopy in daily ENT practice.
AB  - Videostroboscopy has now left specialized voice laboratories and must be made
      available to general ENT practice. It is based on an optical illusion giving the
      impression of slow motion from a series of successive vocal cycles but it is the
      least awkward system to examine the movement of vocal folds while waiting for the
      development of very high speed video recordings which would enable to visualize a
      real single cycle. The equipment comprises a stroboscope, a CCD type of camera, a
      video recorder, a microphone, a monitor or television screen and rigid optics
      and/or a fiberscope. An examination lasts about 1/2 an hour and must follow a
      protocol for which we have developed a simplified index card based on the one
      proposed by HIRANO and B less. This simplified version has the advantage of being
      easily integrated into daily ENT practice. A visual examination of the larynx was
      carried out on 732 patients. Videostroboscopy was undertaken in 69.2% of cases
      and was found to be useful or essential in 68% of the cases where it was carried
      out. Furthermore, it enabled to correct a diagnosis in 13% of these cases. It was
      especially performed in the assessment of benign organic pathologies where
      associated pathologies have to be looked for (nodules--87.7%; REINKE's edema-
      72.2%; mucosal cysts--92.6%; sulcus and scars--83.3%), as well as for tumors
      (73.7%). Among the dysfunctional pathologies, it was principally carried in cases
      of hypokinetic dysphonia (87.7%). Videostroboscopy is a pertinent examination
      because, when it was used, it enabled to modify the initial diagnosis in 17% of
      dysfunctional dysphonias, 20% of nodules, 23% of REINKE's edemas and 17% of
      granulomas.

PMID- 9001637
TI  - The perceptual evaluation of voice disorders.
AB  - The consent about the necessity of perceptual evaluation in the assessment of
      patients with voice disorders is almost unanimous. This is not the case with
      regard to the method or scale. This article gives an outline of historical
      backgrounds and presents a survey of contemporary perceptual rating scales.
      Reliability and influencing factors are discussed and recommendations are made
      with respect to clinical use.

PMID- 9001638
TI  - Aerodynamic measurements of voice production.
AB  - This article reviews measurement techniques, normative results and clinical uses
      of the aerodynamic voice measures maximum phonation time (MPT), vital capacity
      (VC) and phonation quotient (PQ). Variations in measurement procedures have
      proven to yield different results. Simple test techniques have resulted in the
      following normative data: 22.2 sec for MPT, 4800 ml for VC, 269 ml/sec for PQ in
      adult men, and 18.4 sec for MPT, 3500 ml for VC and 233 ml/sec for PQ in adult
      women. None of the three parameters can be used to diagnose voice disorders, but
      each of them is useful for evaluating their degree and for monitoring their
      evolution. MPT appears to be the most sensitive measure of the three.

PMID- 9001639
TI  - Phonetography in voice diagnoses.
AB  - Phonetography has been defined by SCHUTTE and SEIDNER in 1983. Nevertheless
      publications on phonetography go back to the thirties. Due to publications in the
      last decade and the development of computer phonetography this testing method has
      been used for various purposes in voice evaluation. This article gives a
      historical background, with the different ways of phonetogram recording and
      describes variables who have their effect on phonetogram results and
      interpretation. Secondly the range of application with normative and reference
      phonetograms is discussed.

PMID- 9001640
TI  - An introduction to computerised speech lab.
AB  - The need for standardised objective figures exists in speech pathology. This can
      be provided by a computerised technique, the computerised speech lab (CLS), which
      performs an acoustic analysis of the voice samples and gives objective figures of
      multiple parameters.

PMID- 9001641
TI  - Research work of the Belgian Study Group on Voice Disorders 1996. Materials and
      methods.

PMID- 9001642
TI  - Research work of the Belgian Study Group on Voice Disorders 1996. Results.

PMID- 9001643
TI  - Comments to the BSGVD: results from aerodynamic measurements.

PMID- 9001644
TI  - Comment on the results of voice analysis.

PMID- 9001645
TI  - Comparison of the results of the frequency and the intensity data of the BSGVD
      with phonetogram characteristics.

PMID- 9001647
TI  - Maternal smoking and feto-infant mortality: biological pathways and public health
      significance.
AB  - Smoking during pregnancy has in many countries replaced poverty as the most
      important preventable risk factor for an unsuccessful pregnancy outcome. Maternal
      smoking induces fetal hypoxia and morphological changes in the placenta, which
      increase the risks of intrauterine growth retardation and placental abruption,
      which may cause late fetal death and possibly also neonatal mortality. Smoking
      influences post-neonatal mortality through increased risk of sudden infant death
      syndrome (SIDS), but why maternal smoking increases the risk of SIDS is
      essentially unknown. In reducing the overall smoking prevalence in society,
      general preventive measures have been successful. Such measures, which aim at
      preventing young girls from starting to smoke are in the long run the most
      effective way to reduce smoking during pregnancy.

PMID- 9001648
TI  - Taurine supplementation prevents hyperaminoacidemia in growing term infants fed
      high-protein cow's milk formula.
AB  - Blood urea nitrogen (BUN) and plasma and urine amino acid concentrations were
      compared between three cohorts of healthy growing term infants who were breast
      fed (BF) or randomly assigned to one of two formulas either taurine non
      supplemented (FF) or taurine supplemented (FF + T). The infants were studied from
      2 to 12 weeks of age. Weight gain and growth in length was normal and similar in
      all three feeding groups during the study interval. At 12 weeks BUN was
      significantly higher in the FF group than in the BF and FF + T groups, 16.5 mg/dl
      vs 7.0 and 7.3 mg/dl, respectively. Total plasma amino acids (FF group: 240.5 +/-
      110.1 mumoles/dl; BF group 180.1 +/- 28.7 mumoles/dl; FF + T group: 182.3 +/-
      89.4 mumoles/dl) and total essential amino acids (FF group: 89.8 +/- 37.3
      mumoles/dl; BF group: 56.1 +/- 16.3 mumoles/dl; FF + T group: 53.0 +/- 24.2
      mumoles/dl). The urine amino acid concentrations reflected the plasma levels in
      all groups. These results indicate that taurine supplementation to a high protein
      formula lowers BUN levels and the plasma urine amino acid concentrations by some
      yet unknown mechanism to concentrations similar to those found in breast-fed
      infants with a much lower protein intake.

PMID- 9001646
TI  - Pharmacokinetics and renal function in preterm infants.
AB  - There is an increase in the survival rate of preterm infants due to rapid
      advances in medical knowledge and technology. However, the research and attention
      paid to the proper use of pharmacotherapy in these infants is still a relatively
      underdeveloped field. Effective and safe drug therapy requires a thorough
      understanding of human developmental biology and of the dynamic ontogeny of drug
      absorption, drug disposition, drug metabolism, and drug excretion. It is apparent
      that maturation of organ system function and changes in body composition during
      gestation and during the neonatal period exert a significant effect on the
      disposition of drugs. This review focuses on the effects of maturational and drug
      induced changes in renal function on clinical pharmacokinetics in the preterm
      infant.

PMID- 9001649
TI  - Growth hormone in combination with anabolic steroids in patients with Turner
      syndrome: effect on bone maturation and final height.
AB  - Twenty patients with Turner syndrome (CA 7.3-16.4 years) were treated with growth
      hormone (GH) alone (12-18 IU/m2/week) for 0.9-2.5 years. Subsequently, all
      patients received GH 18 IU/m2/week in combination with oxandrolone (Ox) (0.0625
      mg/kg/day po) or low dose testosterone (5 mg every 2 weeks, i.m.).
      Ethinylestradiol (50 ng/kg/day po) was started with a bone age of 12.5 "years",
      and the dose was increased stepwise to 200 ng/kg/day during the next 18 months.
      Final height (FH) after 4-7.7 years of therapy was 152.9 +/- 3.5 cm (range 145.0
      158.9 cm). When compared to projected adult height (PAH) at start of therapy
      (143.7 +/- 4.0, range 137.5-151.0 cm), the estimated benefit from therapy (FH
      minus PAH) is 9.3 +/- 4.9 cm (range 1.4-21.4 cm). The wide range in individual
      responses may be due to over- or underestimation of PAH before therapy due to
      variable delay in bone age at start of therapy. FH did not differ between
      starting therapy before 11.5 years (n = 9; 152.0 +/- 3.4 cm) and after the age of
      11.5 years (n = 11; 153.7 +/- 3.6 cm), due to the fact that a better short-term
      response to therapy in the younger group of patients was compensated for by a
      faster progression in bone age. The good result in terms of final height may be
      due in part to the late start (BA 13.3 +/- 0.4 years; range 12.7-14.5 years) of
      estrogen therapy in low doses.

PMID- 9001650
TI  - Congenital permanent diabetes: a different type of diabetes?
AB  - OBJECTIVE: To investigate two related children with congenital permanent
      diabetes. SUBJECTS AND METHODS: Two related male patients of Arab origin with
      congenital permanent diabetes were studied for immunological and genetic markers,
      insulin and glucagon secretion, thiamine levels, pancreatic ultrasounds studies
      and developmental characteristics. RESULTS: Both patients developed normally. The
      immunological markers were negative, there was no ketosis at diagnosis, and both
      patients were negative for diabetes susceptibility alleles at the HLA locus.
      Insulin levels were undetectable, glucagon secretion, thiamine levels and
      pancreatic ultrasound studies were normal. CONCLUSIONS: Congenital permanent
      diabetes is an extremely rare entity that differs from type I or type II
      diabetes. Our patients have a unique disorder with isolated beta cell defect and
      no additional manifestations. Autosomal recessive inheritance is suggested.

PMID- 9001651
TI  - Dose-dependent effects of oral acyclovir in the incubation period of varicella.
AB  - Dose of acyclovir (ACV) and clinical features of varicella were evaluated in 65
      household contacts (0.8-9 y) who received oral ACV (5-80 mg/kg daily in four
      divided doses) during the latter half of the incubation period of varicella. The
      severity of the disease was compared with that of 23 children who did not receive
      ACV. Infection was confirmed by a fluorescent antibody to membrane antigen assay.
      The antibody titers and the rate of apparent infection increased as the dose of
      ACV administered decreased. The number of skin lesions in patients who received
      ACV was significantly reduced when compared to the control group. These data
      suggest dose-dependence of ACV for modification of varicella during secondary
      viremia in the incubation of the disease.

PMID- 9001652
TI  - Endotracheal suctioning causes right upper lobe collapse in intubated children.
AB  - OBJECTIVE: Right upper lobe collapse is a common radiographic finding in
      intubated children. We hypothesized that deep suctioning and uncontrolled
      negative pressures during endotracheal tube suctioning were significant
      contributory factors. METHODS: The incidence of right upper lobe (RUL) collapse
      in intubated, ventilated children on a paediatric cardiac intensive care unit was
      determined over a 3-month period (n = 102). Graduated suction catheters and
      suction vacuums of < 165 cm H2O were then introduced. Another prospective audit
      was carried out 3 months later (n = 60). RESULTS: We found that 24% developed RUL
      collapse and 4 developed an apical pneumothorax. Following the introduction of
      graduated catheters and controlled vacuums pressures; a significant reduction in
      the incidence of RUL collapse, to 7%, was observed (p < 0.05). CONCLUSIONS: We
      conclude that high negative pressure and deep-suctioning causes RUL collapse in
      children. Any lobar collapse not only prolongs the child's stay in intensive
      care, but can be associated with further morbidity which may have a serious
      implication. By improving suctioning technique this morbidity can be
      significantly reduced.

PMID- 9001653
TI  - Essential fatty acid deficiency and predisposition to lung disease in cystic
      fibrosis.
AB  - Essential fatty acid (EFA) deficiency is a predisposing factor for pulmonary
      infection with Staphylococcus aureus and Pseudomonas aeruginosa, the two major
      pathogenic microorganisms in cystic fibrosis (CF). OBJECTIVE: The goal of this
      study was to investigate the essential fatty acid status of CF patients from
      infancy to 20 years old. MATERIALS AND METHODS: Plasma fatty acid profiles for
      phospholipid (PL) were determined for cord (n = 6), 4 months (n = 40), 16 months
      (n = 25), 3 y (n = 8), 5-10 y (n = 10), and 10-20 y (n = 10) aged CF patients and
      compared to their respective control; cord (n = 22), 1-36 months (n = 38) and
      adult (n = 100). Significance was established by Student's t-test (p < 0.05).
      RESULTS: The plasma PL fatty acid profile for all CF patients, except cord,
      revealed consistent deficiency in omega 3 and omega 6 EFAs. These deficiencies
      were most marked at infancy and more pronounced for patients with meconium ileus.
      CONCLUSIONS AND RELEVANCE: EFA deficiency may contribute to the predisposition of
      CF infants to develop respiratory disease and to the excess cytotoxic activity
      found in bronchoalveolar lavage fluid at 2 months of age in the majority of
      screened infants.

PMID- 9001654
TI  - Low back pain and its relationship to back strength and physical activity in
      children.
AB  - OBJECTIVE: The objective of the study was to determine the occurrence of low back
      pain and its relationship to back strength and physical activity in children.
      METHODS AND MATERIALS: The study included 53 boys and 43 girls aged 10 to 19
      years from a group of 116 children who had undergone isometric strength testing 4
      years previously. No intervention was performed. Each child was asked five
      questions concerning low back pain. A questionnaire to quantify participation in
      athletic activities and manual labor was used as the basis for calculation of
      each child's activity level. Isometric back flexor and extensor strength were
      measured with the same method used 4 years previously. Statistical analyses were
      performed with appropriate correction for confounding factors. RESULTS: The
      frequency of low back pain and the relationship between low back pain and age,
      between low back pain and back strength, and between low back pain and physical
      activity were determined. There was a history of low back pain in 51%, and the
      frequency of low back pain in the past year was 35%. Eight percent of the
      children had been limited by low back pain, and 7% had seen a doctor for the
      pain. The first incident of low back pain occurred at a mean age of 12.3 years.
      The frequencies of a history of low back pain and of low back pain in the past
      year increased significantly with age (p = 0.02 and 0.01 respectively). Increased
      physical activity was significantly associated with a history of low back pain (p
      = 0.03), and increased back flexor strength was significantly associated with a
      history of low back pain and of low back pain in the past year (p = 0.03 and
      0.008, respectively). The rate of low back flexor or strength over 4 years had a
      significantly positive association with the occurrence of low back pain in the
      past year (p = 0.008). CONCLUSIONS AND RELEVANCE: Low back pain is common in
      children, and, in contrast to adults, low back pain in these children was more
      common with increased physical activity and stronger back flexors. We believe the
      main causes of low back pain in children are musculotendinous strains and
      ligamentous sprains.

PMID- 9001655
TI  - Long-term follow-up of indirect hyperbilirubinemia in full-term Turkish infants.
AB  - OBJECTIVE: This retrospective follow-up study was performed to evaluate the
      suitability of the recently reported exchange transfusion limits (serum indirect
      bilirubin level of 428-496 mumol/1, 25-29 mg/dl) for Turkey. MATERIAL AND
      METHODS: The study groups totalled 102 children, 8-13 years of age, who had been
      born at term with birthweights greater than 3000 g and had been treated for
      indirect hyperbilirubinemia during their newborn period; the control group
      consisted of 27 children of the same age-group without indirect
      hyperbilirubinemia. Children were grouped according to their maximum serum and
      bilirubin levels and direct Coomb's test results. Physical and neurological
      examinations, visual and brainstem auditory evoked potentials and the Wechsler
      Intelligence Scale for children--Revised for Turkish Children were performed.
      RESULTS: There was no difference between the groups with regard to mean visual
      and brainstem auditory evoked potential latencies. Children whose direct Coomb's
      tests were positive had significantly lower IQ scores and more prominent
      neurological abnormalities (p < 0.05). IQ scores and prominent neurological
      abnormalities did not differ among the other groups. Nine children had prominent
      neurological abnormalities associated with abnormal brainstem auditory evoked
      potentials. An important risk factor was the duration that the infant's serum
      indirect bilirubin level remained greater than 342 mumol/l (20 mg/dl).
      CONCLUSION: The current limit of 342 mumol/l should continue to be used for
      infants whose direct Coomb's tests are positive in our country. Until better
      criteria for exchange transfusion other than the indirect bilirubin level are
      established, the current limits should also still be followed for infants whose
      direct Coomb's tests are negative in Turkey, where regular neonatal follow-up
      examinations are not satisfactory.

PMID- 9001656
TI  - Transient dystonia in non-handicapped low-birthweight infants and later
      neurodevelopment.
AB  - The aim of the present study was to evaluate the long-term prognostic
      significance of transient increase in muscle tone during infancy (dystonia) in
      very low-birthweight (VLBW) infants without cerebral palsy. Motor (Peabody
      Developmental Motor Scales), cognitive (Wechsler Preschool and Primary scale of
      Intelligence) and behavioural (Personality Inventory for Children, Yale
      Children's Inventory) development was assessed at 5 years of age. In a population
      based sample of 50 VLBW children, transient dystonia was present in 14. In
      explorative analyses, transient dystonia was associated with low 1 min Apgar
      scores, neonatal bacterial infection, and lack of breast-milk in the neonatal
      period. Cognitive, neuromotor and behavioural development at 5 years of age was
      comparable in those with and without transient dystonia, although there was a
      statistically non-significant tendency towards more neuromotor problems in the
      dystonic children.

PMID- 9001657
TI  - Home visiting the newborn baby as a basis for developmental surveillance at child
      welfare centres.
AB  - Home visiting is a part of the Swedish child health surveillance programme. In
      the present study, part of a longitudinal prospective project, the predictive
      power of observations at home visits to 338 newborn babies was evaluated. The
      regular home visit was made by the nurse at a Child Welfare Centre also using a
      check-list developed for this project. Her check-list assessments seemed valid in
      identifying families with stressful psychosocial conditions. When the general
      home situation was judged as "poor" or "dubious", the boys showed signs of a
      delayed mental development at 4-5 years of age. Assessments of "feeding problems"
      among boys were associated with behavioural problems at 4-5 years of age. The
      results underline the importance of an early home visit as a base for the
      developmental surveillance at Child Welfare Centres. However, the results of the
      home visit observations were not followed by any extra interventions at CWC. It
      seems the nurse should feel confident in her check-list judgement and initiate
      interventions where appropriate.

PMID- 9001658
TI  - Growth hormone status in six children with fetal alcohol syndrome.
AB  - OBJECTIVE: Prenatal alcohol exposure may cause fetal alcohol syndrome (FAS),
      which is associated with pre- and postnatal retardation. MATERIALS AND METHODS:
      Spontaneous 24-h growth hormone (GH) secretion was measured in six prepubertal
      short children with FAS (two boys and four girls) aged 4-14 years. The response
      to a GH stimulation test, and levels of insulin-like growth factor-I (IGF-I) and
      IGF-binding protein-3 (IGFBP-3) were also measured. Comparisons were made between
      the children with FAS and healthy children of both normal and short stature, as
      well as children born small for gestational age (SGA). RESULTS: There were no
      differences in the mean area under the curve above the baseline or the maximum
      level of GH during a 24-h period (GHmax) between the children with FAS and the
      reference groups. However, the estimated rate of spontaneous 24-h GH secretion in
      children with FAS was similar to that of children born SGA, but lower than in
      children of normal stature (p = 0.02). The plasma concentrations of IGF-I and
      IGFBP-3 were in the lower parts of the normal range. CONCLUSION: We conclude that
      GH secretion in short children with FAS is similar to that in short children born
      SGA; that is, in the lower range of normal children.

PMID- 9001659
TI  - Paediatric and ophthalmologic observations in offspring of alcohol abusing
      mothers.
AB  - The offspring of nine women who had abused alcohol and drugs during pregnancy
      were studied. Of the 30 children, 10 had fetal alcohol syndrome (FAS) or fetal
      alcohol effects (FAE). Ophthalmological impairments associated with FAS--impaired
      vision, optic nerve hypoplasia, cataract, increased tortuosity of retinal vessels
      -were common. The severity of teratogenic lesions varied among the children and
      was often related to the level of abuse during pregnancy. Most women were unable
      to take care of their children during periods of substance abuse. All children
      with FAS/FAE had learning difficulties. Four mothers abstained from alcohol or
      drugs during some of their pregnancies and gave birth to children without birth
      defects.

PMID- 9001660
TI  - Studies on nutrition in severely neurologically disabled children in an
      institution.
AB  - Severe neurological handicaps in children are frequently accompanied by growth
      retardation. We have studied 13 severely neurologically impaired children in an
      institution to see if their poor growth was related to a low intake of energy and
      nutrients, if this was reflected in biochemical nutritional parameters, and to
      modify their diet according to the results. The investigation showed low dietary
      intakes of energy and of several of the nutrients, with corresponding low Hb
      values and serum values of ferritin, selenium and vitamins E and D in some of the
      children. All the children were initially light for age, with catch-up growth
      after intervention. We conclude that severely disabled children are at high risk
      for under- and malnutrition, and that this may partly explain the growth
      retardation in the study group. To avoid the potential detrimental effects of
      malnutrition, it is important to aim at providing an optimal diet.

PMID- 9001662
TI  - An investigation into the physical stability of a neonatal parenteral nutrition
      formulation.
AB  - The physical stability of a neonatal parenteral nutrition formulation has been
      examined using differential interference contrast (DIC) microscopy. In vitro
      studies indicated that particle size increases occur immediately after mixing the
      Intralipid emulsion with the amino acid/glucose solution, while simulation of
      clinical administration indicated that larger droplets were observed at the end
      of the catheter approximately 1 h after administration commenced. Microscopic
      observation of adjacent droplets of the two fluids showed reversible aggregation
      occurring almost immediately. It was concluded that the current method of
      administering this neonatal emulsion does not prevent droplet coalescence.

PMID- 9001661
TI  - Ethnic variation of cord plasma apolipoprotein levels in relation to coronary
      risk level: a study in three ethnic groups of Singapore.
AB  - In multiracial Singapore, the prevalence of coronary artery disease is highest in
      ethnic Indian and lowest in ethnic Chinese populations. Since susceptibility to
      coronary artery disease is closely associated with plasma lipid traits, we
      studied the cord blood lipid and apolipoprotein profiles of the three ethnic
      groups in Singapore to determine if ethnic differences in lipid profile are
      present at birth. The high-risk lipid traits of high LDL-cholesterol,
      triglycerides and apo B, low HDL-cholesterol and apo A-I were found to be highest
      in ethnic Indian and lowest in ethnic Chinese populations. This difference was
      concordant with the relative coronary mortality rates for their respective adult
      populations in Singapore.

PMID- 9001663
TI  - Catabolic effect in premature infants with early dexamethasone treatment.
AB  - To evaluate the catabolic effects of dexamethasone therapy on protein metabolism,
      amino acid concentrations and urinary 3-methylhistidine (3MH) were measured in 28
      premature infants who were included in a double-blind controlled study using
      early dexamethasone therapy in the prevention of bronchopulmonary dysplasia.
      Fifteen infants received dexamethasone (0.5 mg/kg/day i.v.) and 13 infants
      received normal saline as control. Heparinized venous blood samples for amino
      acid analysis were obtained before the study and again at day 5 after starting
      the study. Urinary 3MH was measured on days 1, 3, 5, 7, 14, 21, and 28 of
      treatment. A substantial increase in amino acid concentrations was observed in
      infants receiving dexamethasone. Alanine, glutamine, citrulline, ornithine and
      cystine concentrations increased twofold or more. The 3MH:creatinine ratio was
      increased in the treated group. These metabolic effects were most likely due to
      an increase in protein catabolism.

PMID- 9001664
TI  - Less severe retinopathy of prematurity induced by surfactant replacement therapy.
AB  - To assess the effect of surfactant replacement therapy (SRT) on the prevalence
      and severity of retinopathy of prematurity (ROP), we compared data from 160 SRT
      treated preterm infants with data from 230 historic controls. The prevalence of
      ROP was 30.6% in the treatment group and 23.4% in the control group. Severe ROP
      (stages 3-4) was seen in 6.1% of the infants with ROP in the treatment group and
      20.3% of the ROP patients in the control group. Surfactant therapy had no
      influence on the prevalence of ROP (odds ratio 1.4, 95% confidence interval 0.797
      2.459, p = 0.242). However, SRT was associated with a decreased risk for severe
      ROP, compared to mild ROP (odds ratio 0.226, 95% confidence interval 0.056-0.905,
      p = 0.036). These data suggest that SRT is associated with a decreased risk for
      severe ROP.

PMID- 9001665
TI  - Use of tolazoline to counteract vasospasm in peripheral arterial catheters in
      neonates.
AB  - Arterial access for blood sampling and continuous blood pressure monitoring is
      the cornerstone of modern neonatal intensive care. Although umbilical arterial
      catheters have traditionally been utilized for arterial access, they are
      associated with potentially devastating complications. Consequently, there has
      been an increase in the use of peripheral arterial catheters. Unfortunately,
      these catheters have a limited useful lifespan secondary to vasospasm, intimal
      damage and/or thrombus formation. In this report, we describe the use of
      tolazoline (0.02 to 0.2 mg/kg/h) to counteract local arterial vasospasm in five
      critically ill neonates, where arterial access was vital for care but difficult
      to maintain.

PMID- 9001666
TI  - Breastfeeding pattern in a population with different levels of poverty in
      Southern Brazil.
AB  - A cross-sectional study was conducted on 477 poor children aged 12-59 months in
      order to investigate their breastfeeding pattern, taking into account the poverty
      level of their families. Although the population living in extreme poverty had
      the same pattern of breastfeeding as the rest of the poor population, the former
      group should still have priority in breastfeeding promotion programs, since they
      are the population who benefit most with breastfeeding.

PMID- 9001667
TI  - Transient hepatitis B surface antigenemia after neonatal hepatitis B
      immunization.
AB  - Following immunization with hepatitis B vaccine, 39 infants were followed
      prospectively for hepatitis B surface antigen (HBsAg). A total of 69.2% of the
      infants tested positive for antigenemia at least once. Antigenemia was identified
      most often at 2-3 days (43.5%) and 5-6 days (43.5%) after immunization. The
      longest documented duration of antigenemia was 21 days. In all cases the
      antigenemia was transient and cleared by 28th day post-vaccination.

PMID- 9001668
TI  - Down syndrome and coeliac disease: usefulness of antigliadin and antiendomysium
      antibodies.
AB  - The usefulness of antigliadin (AGA) and antiendomysium antibodies (EMA) as a
      screening test for coeliac disease (CD) in 113 Down syndrome (DS) patients (61
      children) was evaluated. AGA IgA were present in 22.1%, AGA IgG in 48.6%, EMA in
      6.2%. Four symptomatic patients, AGA- and EMA-positive, were affected by CD
      (3.5%). In three AGA-positive and EMA-positive subjects, permission for
      intestinal biopsy was refused, while in two AGA-positive and EMA-negative
      children, the intestinal mucosa was normal. Our study confirms the association of
      CD and DS, and suggests the usefulness of EMA determination as a test for
      selecting DS patients for intestinal biopsy.

PMID- 9001670
TI  - Transient hypertriglyceridemia of infancy.
AB  - A premature boy who had suffered from IRDS, bronchopulmonary dysplasia and
      retinopathy of prematurity developed massive hypertriglyceridemia (48.1 mmol/L)
      together with moderate hypercholesterolemia (12.6 mmol/L) at 5 months of age.
      Lipoprotein electrophoresis revealed a marked elevation of the level of the very
      low density lipoprotein fraction. There was a moderate decrease in the activity
      of a lipolytic enzyme, lipoprotein lipase (LPL). The child had neither liver or
      renal disorder nor any inflammatory disease. The hyperlipidemia disappeared
      spontaneously at the age of 3 years. The cause of the decreased LPL activity
      could not be established. A partial genetic deficiency in lipoprotein lipase
      appears the most likely explanation, since no signs of secondary lowering of LPL
      activity could be found.

PMID- 9001669
TI  - Achondroplasia in Sweden caused by the G1138A mutation in FGFR3.
AB  - Achondroplasia, an autosomal dominant inherited disorder, is one of the most
      common forms of skeletal dysplasia resulting in disproportionate extreme
      shortness. Recently, two point mutations, both affecting nucleotide 1138 in the
      fibroblast growth factor receptor type 3 (FGFR3) gene, were found to be the cause
      of the disorder. We investigated DNA from 16 Swedish patients with achondroplasia
      for the presence of these mutations. All patients were found to be heterozygous
      for the G to A transition at nucleotide 1138. Our data thus support previous
      reports showing a striking genetic homogeneity, in that almost all achondroplasia
      patients have the FGFR3 G380R mutation at the protein level.

PMID- 9001672
TI  - Sudden infant death syndrome.

PMID- 9001671
TI  - Fatal outcome of disseminated Mycobacterium avium infection in childhood. A case
      of primary incompetent monocyte/macrophage function?
AB  - Disseminated BCG infection rarely heals, and disseminated disease caused by the
      Mycobacterium avium complex usually has a poor prognosis with a short time to
      death. The case of a boy who died after 9 years of diagnosed disseminated M.
      avium complex infection is described. He showed no signs of previously known
      immunodeficiency except an incompetent primary monocyte/macrophage function. This
      case has been commented on in Acta Paediatrica Scandinavia (1982) as "the first
      infant to survive a generalized BCG infection".

PMID- 9001673
TI  - Classification of SIDS.

PMID- 9001674
TI  - Respiratory pattern of newborn infants exposed to heat stress.

PMID- 9001675
TI  - Metabolic alkalosis.

PMID- 9001676
TI  - Central venous catheters.

PMID- 9001678
TI  - Functional results of percutaneous laser discectomy.
AB  - The purpose of the study was to evaluate laser disc decompression with the KTP
      532 laser, used in conjunction with a percutaneous technique, in contained, small
      to moderately sized lumbar disc herniation. Sixty-three patients who had a
      contained herniated nucleus pulposus (HNP) and underwent percutaneous laser disc
      decompression were prospectively studied. Sixty-one were available for follow-up.
      Access to the disc space was attained with an 18-gauge probe, followed by
      dilating cannulas guided with an image intensifier. Discography was not
      performed. The power was set at 10 W, and laser pulses were delivered for 0.2
      seconds, with an interval of 0.5 seconds. A total of 1250 J was delivered to the
      disc space. The average follow-up was 31.75 months (range, 20 to 45 months).
      Overall, 44 patients (72%) achieved relief of radicular pain, and 33 patients
      (54%) achieved relief of low back pain. Thirty-six of 61 patients (59%) returned
      to work by postoperative week 4. Fourteen patients failed treatment, experiencing
      persistent symptoms (with scores on the Andrews and Lavyne rating scale of < or =
      3). In this study group, optimal results were obtained when symptoms were treated
      within 1 year of presentation. Results from a historical control group are
      provided for comparison.

PMID- 9001677
TI  - The piriformis syndrome.
AB  - Piriformis syndrome is an often misdiagnosed cause of sciatica, leg, or buttock
      pain, and disability. The sciatic nerve may be compressed within the buttock by
      the piriformis muscle, with pain increased by muscular contraction, palpation, or
      prolonged sitting. A thorough medical history and physical examination are
      essential to proper diagnosis. Diagnostic testing may be used to differentiate
      piriformis syndrome from other causes of sciatica, lower extremity weakness, and
      pain. This article reviews the pathophysiology and management of piriformis
      syndrome.

PMID- 9001679
TI  - Initial stability of a modular uncemented, porous-coated femoral stem: a
      mechanical study.
AB  - A versatile modular hip system was used to evaluate the initial stability of a
      cementless femoral stem in anatomically consistent composite bones. Four implant
      bone configurations of varying proximal and distal fit/fill were tested. The
      implanted femurs were tested on an Instron 1331 materials testing machine in
      neutral loading and flexion loading; both translational micromotions and
      rotations of the implant relative to the bone were recorded on all three axes of
      motion, accounting for all 6 degrees of freedom of joint motion. Implants were
      then sectioned, and both endosteal canal fit and intramedullary canal fill were
      measured. Results indicate that (1) loading the implant in flexion by out-of
      plane forces significantly increases both relative translation and rotation at
      the interface, (2) increasing the proximal fit reduces implant rotation about its
      longitudinal axis in flexion loading and (3) increasing the distal canal fit and
      fill increases prosthesis rotation about its longitudinal axis in flexion
      loading. These results indicate that the femoral stem is more unstable in out-of
      plane loading, such as during stair climbing, and that increasing the proximal
      fit may enhance the initial rotational stability of an uncemented femoral stem.

PMID- 9001680
TI  - Two-level dorsal dislocation of the little finger.
AB  - The case of an elderly man who suffered simultaneous interphalangeal joint
      dislocation in one finger as a result of a hyperextension force on both the
      distal and proximal interphalangeal joints is presented. This case differs from
      the few reports of this type of injury in the literature both in its mechanism of
      injury and time to reduction. Most reports have been in athletes who are actively
      involved in a sport, whereas the present case was the result of a fall. Also,
      successful reduction was achieved almost 2 weeks postinjury, indicating that,
      even with this amount of delay, these injuries can be effectively treated with
      closed reduction.

PMID- 9001681
TI  - Synovial Osteochondromatosis of the elbow presenting with ulnar nerve neuropathy.
AB  - Synovial chondromatosis is an uncommon disorder in which cartilaginous material
      is formed within synovial tissue. The cartilaginous nodules may undergo
      enchondral ossification, described as synovial osteochondromatosis. The nodules
      may be shed from the synovium and become intra-articular loose bodies. The
      presenting symptoms are usually diffuse discomfort in the affected joint and
      decreased range of motion with an accompanying gritty or locking sensation. The
      authors present the case of a young man with elbow synovial osteochondromatosis
      associated with ulnar nerve neuropathy.

PMID- 9001682
TI  - "Neurologic manifestations of cumulative trauma disorder".

PMID- 9001683
TI  - Metastatic malignant chondroblastoma.
AB  - A case of malignant chondroblastoma with metastases is reported. The patient
      initially presented with a lytic lesion in his left pubic ramus. He was treated
      with curettage, but the lesion recurred 3 years later. After repeated curettage,
      radiation therapy, and the late development of multiple bone and soft-tissue
      metastases, he succumbed to his disease 13 years after diagnosis. The surgical
      pathology from each of his several procedures was reviewed. Although no definite
      malignant transformation was apparent, a metastatic deposit curetted 3 months
      prior to death showed some increase in mitotic activity. Flow cytometry of
      specimens from the patient's first local recurrence and a late distant metastasis
      was performed and revealed the interval development of a minor aneuploid peak
      between the two samples. This fatal chondroblastoma is the only one in our series
      of 80 patients treated over the past 25 years.

PMID- 9001684
TI  - Consumption of eggs with meals increases the susceptibility of human plasma and
      low-density lipoprotein to lipid peroxidation.
AB  - Consumption of eggs for a long period was shown to result in hypercholesterolemia
      and is generally restricted for this reason. In the present study we analyzed the
      effect of eggs consumption for 3 weeks on lipoprotein atherogenicity. Consumption
      of 2 eggs per day with the meals, for 3 weeks resulted in a minor elevation in
      plasma glucose and urea concentrations. Plasma cholesterol concentration
      increased by 11% (p < 0.05) as a result of increased plasma low-density
      lipoprotein (LDL) cholesterol levels. Plasma triglycerides decreased by 13% (p <
      0.01), but there were no significant alterations in plasma apolipoproteins A-I or
      B-100 concentrations. Plasma high-density lipoprotein (HDL) cholesterol decreased
      by 11% (p < 0.05). There was a 13% reduction, though not significant, in the
      cholesterol efflux from J-774 A.1 macrophages by HDL that was derived after eggs
      consumption in comparison to HDL that was obtained at baseline. The
      susceptibility of plasma [using 100 mM of 2,2' azobis 2-amidinopropane (AAPH)] as
      well as that of LDL (using 10 microM of copper ions) to lipid peroxidation was
      increased by 42% and 34%, respectively, as measured by the thiobarbituric acid
      reactive substance (TBARS) assay (p < 0.01). Kinetic analysis of LDL oxidation by
      copper ions revealed a 37% reduction in the lag time required for the initiation
      of LDL oxidation after 3 weeks of eggs consumption. The total plasma fatty acids
      concentration increased from 2.2 +/- 0.5 to 3.2 +/- 0.6 mg/ml. The plasma
      antioxidants, vitamin E and carotenoids were not significantly affected by eggs
      consumption. We conclude that eggs consumption, in addition to its
      hypercholesterolemic effect, increases plasma and LDL oxidizability, a phenomenon
      which was shown to enhance the progression of atherosclerosis. The atherogenic
      properties may contribute to the accelerated atherosclerosis prevalent in
      populations with high cholesterol intake.

PMID- 9001686
TI  - Effects of docosahexaenoic acid and sardine oil diets on the ultrastructure of
      jejunal absorptive cells in adult mice.
AB  - The influence of docosahexaenoic acid (DHA) and sardine oil diets on the
      ultrastructure of jejunal absorptive cells was studied. Adult male Crj:CD-1 (ICR)
      mice were fed a fat-free semisynthetic diet supplemented with 5% (by weight)
      purified DHA ethyl ester, refined sardine oil, or palm oil. The mice received the
      DHA or palm oil diets for 7 days (groups 1 and 2) and the refined sardine oil or
      palm oil diets for 30 days (groups 3 and 4). There were significant
      ultrastructural changes in the jejunal absorptive cells between the mice fed on
      the palm oil diet and those receiving the DHA and sardine oil diets. The
      endoplasmic reticulum and Golgi apparatus of some jejunal absorptive cells in the
      mice fed on the palm oil diet for 7 and 30 days developed vacuolation on the
      upper site of the nucleus. In contrast, many granules, which appeared to be lipid
      droplets, were observed in the endoplasmic reticulum and Golgi apparatus of the
      jejunal absorptive cells in the DHA and sardine oil diet groups. These results
      suggest that ultrastructural differences in the jejunal absorptive cells between
      mice in the omega-3 fatty acid and palm oil diet groups may be associated with
      the changes in lipid metabolism.

PMID- 9001685
TI  - Potential ligands for cell adhesion molecules in human milk.
AB  - In this study, glycoproteins and oligosaccharides with sialyl Lewis a, sialyl
      Lewis x, Lewis x, and Lewis y epitopes were isolated by ultracentrifugation and
      fast-protein liquid chromatography from human milk of mothers with term or
      preterm infants. The identification of these epitopes on whey proteins was
      achieved by monoclonal antibodies and lectins after Western blotting. Lactose
      derived oligosaccharides were characterized by high-performance thin-layer
      chromatography and high-pH anion-exchange chromatography with pulsed amperometric
      detection. These carbohydrate epitopes which are potential ligands for selections
      are not of cellular origin but appear in the soluble fraction of milk. Here, they
      are present as lactose-derived oligosaccharides (molecular weight < 10 kD) or
      bound to proteins with a high molecular weight (> 100 kD). Lewis antigens might
      represent another category of protective nonimmunological substances in human
      milk with the potential to influence inflammatory processes in human milk fed
      infants.

PMID- 9001688
TI  - Folate absorption in the jejunum of chronic ethanol-fed rats: in vivo studies.
AB  - This study sought to determine the intestinal in vivo absorption of folic acid
      and methyltetrahydrofolate (MTHF) by jejunum surface at different times, after 20
      weeks of 30% ethanol ingestion. The absorption results were compared with the
      data of control rats. In general after ethanol treatment jejunal folic acid
      absorption was higher than in control rats. When the folic acid concentrations in
      the perfusion medium were 0.5 microM an increase at later times in ethanol-fed
      rats was found. At 1 microM the folic acid absorption values were significantly
      higher at the earlier time. When the concentration assayed was 2.5 microM,
      significant modifications were only seen at 30 min. Results of MTHF absorption by
      jejunum of ethanol-fed rats were similar to absorption values of control rats. No
      significant differences between both groups were found. The results obtained in
      the present work suggested a different absorptive behavior of both substrates and
      a different effect of ethanol on folic acid and MTHF absorption in the jejunum.

PMID- 9001687
TI  - Dietary fat effects on brush border membrane composition and enzyme activities in
      rat intestine.
AB  - The effect of dietary fats on the chemical composition and enzyme activities has
      been studied in intestinal brush border membranes (BBM) or rats. Animals were
      given commercial rat pellet diet (RP) or semisynthetic diet rich in either
      saturated [coconut oil (CCO))] or polyunsaturated [n-6, corn oil (CO) or n-3,
      fish oil (FO)] fat at the 10% level for 5 weeks. The membrane
      cholesterol/phospholipid ratio was augmented in CO- or RP-fed rats. There was an
      increase in level of saturated fatty acids in BBM from CCO- or FO-fed animals. n
      3 polyunsaturated fatty acid content was raised in FO-fed rats, while the
      proportion of linoleic acid and arachidonic acid was enhanced in animals given a
      CO diet. Membrane fluidity was in the order of CCO < RP = CO < FO. The membrane
      hexose content was high (p < 0.05) in the CCO group. Hexosamines were elevated (p
      < 0.05) in CCO- or FO-fed rat brush borders. Membrane fucose was unaltered, while
      sialic acid content was elevated in CO- (p < 0.05) and FO- (p < 0.01) fed vs. CCO
      fed rats. Lectin binding to brush borders corroborated these findings. The
      activities of alkaline phosphatase, sucrase and lactase were augmented (p <
      0.001) in CCO-fed animals. Leucine-aminopeptidase and sucrase activities were
      depressed by FO feeding. The activities of PNP-beta-glycosidases were the highest
      in FO-fed rats. These results indicate that dietary fat quality markedly affects
      microvillus membrane lipid composition, glycosylation and enzyme functions in rat
      intestine.

PMID- 9001689
TI  - Folate absorption in the caecum of chronic ethanol-fed rats: in vivo studies.
AB  - This study was designed to determine the intestinal in vivo absorption of folic
      acid and methyltetrahydrofolate (MTHF) by the caecum surface at different times
      after 20 weeks of 30% ethanol ingestion. The absorption results were compared to
      the data of control rats. Chow and fluid consumption and body weight were
      significantly lower in ethanol-fed rats. The absorption of folic acid and MTHF by
      the caecum surface (pmol/cm2) was generally decreased in ethanol-fed rats at all
      concentrations assayed with respect to control animals (except for absorption of
      0.5 and 2.5 microM folic acid at 15-min intervals). The results obtained in the
      present work also suggest a different absorptive behaviour of folic acid and MTHF
      in the caecum under the influence of chronic alcohol ingestion.

PMID- 9001690
TI  - Influence of two dairy fats on lipid synthesis in the pig: comparative study of
      liver, muscle and the two backfat layers.
AB  - The development of pig adipose tissues is influenced by several factors such as
      localisation and dietary fat. The neck and backfat subcutaneous adipose tissues
      consist of two layers with different chemical compositions, and it is not yet
      known whether such variations are due to differences in lipogenic enzyme
      activities or to other factors. The aim of the present study was to compare the
      lipogenic activities of tissues from different sites (Longissimus dorsi muscle,
      liver, subcutaneous backfat) and between the outer and inner backfat layers. The
      effects of dietary fat from two animal sources on the lipogenic activities and
      fatty acid composition of these tissues were also compared. 28 Large White x
      Pietrain cross-bred swine, averaging 75 (initial) to 108 kg (final) live weight,
      were allocated into 2 groups. They were fed diets with the same energy and lipid
      contents but provided either by goat's milk or cow's milk. The lipid content and
      fatty acid composition of the tissues were determined and the following lipogenic
      enzymes activities measured: acetyl-CoA carboxylase (CBX); glucose-6-phosphate
      dehydrogenase (G6PDH) and malic enzyme (ME). Both groups showed similar average
      daily gain, carcass composition and tissue lipid contents. Lipogenic activities
      were highest in backfat (p < 0.001), intermediate in Longissimus dorsi muscle and
      lowest in liver. The lipogenic activities in backfat tissue were greater (p <
      0.001) in the inner than in the outer layer in both groups. Animals fed on goat's
      milk exhibited greater (p < 0.05) CBX and ME activities in the backfat, and CBX
      (p < 0.05) activity in the Longissimus dorsi muscle. In backfat tissue of animals
      fed on goat's milk, CBX, G6PDH (p < 0.01) and ME (p < 0.05) were greater in the
      inner than in the outer layer, whereas in animals fed on cow's milk the inner
      backfat layer exhibited the slightly higher (p < 0.05) lipid content. Differences
      in CBX activity between the two dairy diets tended to be greater (p < 0.001) in
      the inner backfat than in the outer layer. This suggests that the inner layer
      might be more sensitive to dietary source fat. It is concluded that the layers of
      pig subcutaneous backfat should not be considered as a single entity, but rather
      as two separate tissues.

PMID- 9001691
TI  - Dietary selenium intake and selenoproteins in rat plasma.
AB  - Selenium (Se) is vital for animals and humans, as it is an essential component of
      Se-dependent glutathione peroxidase (GPx), an enzyme that reduces peroxides and
      protects cells against the damaging effects of oxidation. Se has, however, been
      found in rat plasma even when the enzymatic activity of GPx is very low,
      supporting the hypothesis that Se is also bound to other proteic structures. The
      purpose of this work was partially to purify the selenium-containing proteins in
      plasma, without denaturation, by isoelectrofocusing. We observed two pH intervals
      in the plasma where Se-containing proteins concentrated upon focusing: the first,
      at pH 6.0 +/- 0.2 and with GPx activity, and the second, between pH 4.6 and 5.4,
      with no enzymatic activity. We can infer therefore that other Se-containing
      proteins are present at a lower pH than 6, and in particular between 4.6 and 5.4

PMID- 9001692
TI  - Plasma somatostatin and cholecystokinin levels in preterm infants during the
      first day of life.
AB  - Our knowledge about regulatory gut peptides in preterm infants is scanty. We
      therefore began a study of plasma somatostatin (SS) and cholecystokinin (CCK) in
      preterm infants at birth and during the neonatal period. Plasma SS and CCK levels
      were assessed in 77 mothers and in 91 preterm infants immediately after birth
      (umbilical cord) and during the first day of life (1F) (n = 69, median age 5 h).
      The gestational age ranged from 23 to 36 weeks and the birth weight from 460 to
      3,350 g. After Sep-Pak C18 semichromatography of plasma, SS and CCK were analyzed
      by RIA. Both plasma SS and CCK levels increased significantly during the first
      hours of life. Plasma SS levels were negatively correlated to gestational age,
      birth weight and birth length. When the SS-1F levels were adjusted for
      gestational age in a multivariate analysis there was no independent association
      with birthweight but a weak association with birth length. Plasma CCK-1F levels
      were not correlated with any of these variables. Plasma SS-1F levels were lower
      after cesarean section. Plasma SS and CCK levels during the first day were not
      correlated to multiple birth, mode of anesthesia, umbilical pH, Apgar score and
      blood glucose level before first meal.

PMID- 9001693
TI  - Platelet activation in newborns detected by flow-cytometry.
AB  - Platelet function was investigated in full-term infants on the first, the fourth
      and tenth days of life and compared to normal adult controls. Platelet function
      was analyzed through a new cytofluorimetric technique with two murine monoclonal
      antibodies, PAC-1 and anti-GMP-140, directed against two membrane proteins
      expressed on the activated platelets' surface. The percentage of activated
      platelets detected with PAC-1 and anti-GMP-140 was evaluated at basal condition
      and after in vitro stimulation with a weak agonist (ADP) and a strong Txa2
      analogue inducer (U 46619). At day 1 platelet activation at basal condition was
      negligible and similar to adult controls both with PAC-1 (1.2 vs 1.1%) and anti
      GMP-140 (2.6 vs. 3.3%). On the contrary, after ADP stimulation the percentage of
      PAC-1-positive activated platelets was significantly reduced in neonates compared
      to adults (22 vs. 66%; p < 0.001) and even more after U 46619 (11 vs. 72%; p <
      0.001). The percentage of anti-GMP-140-positive activated platelets behaved
      similarly after adding both ADP (26 vs. 46%; p < 0.01) and U 46619 (37 vs. 67%; p
      < 0.001). The reduced platelet activation after ADP and U 46619 persisted at day
      4 both with PAC-1 and with anti-GMP-140. On the contrary, at day 10 newborn
      platelets analyzed with anti-GMP-140 behaved similarly to the adult ones both at
      basal condition and after stimulation with ADP or U 46619 (6 vs. 3% at basal
      state, 42 vs. 46% after ADP addition, and 55 vs. 67% after U 46619). These data
      demonstrate that the reduced platelet activation present in newborns is restored
      by the tenth day after birth.

PMID- 9001694
TI  - Mid- and long-term outcome of 89 premature infants weighing less than 1,000 g at
      birth, all appropriate for gestational age.
AB  - OBJECTIVE: Advances in obstetrical and neonatal care have achieved dramatic
      reductions in the mortality of extremely low birth weight infants, but concerns
      regarding the long-term neurodevelopmental prognosis have increased. The study
      was performed to assess the physical and developmental status of premature
      infants weighing < 1,000 g at birth who were appropriate for gestational age
      (AGA). METHODS: A follow-up study including school level, physical and
      developmental examination and/or interviews of parents, pediatricians, teachers
      and social workers was carried out from January 1, 1981 to December 31, 1991, on
      176 subjects who had been AGA premature neonates weighing < 1,000 g and were
      admitted to the Port Royal Neonatal Intensive Care Unit. Eighty-nine survived (50
      girls, 39 boys). Five children were lost to follow-up after 3 years of age.
      Neurological sequelae, developmental and/or intellectual quotients, school level
      and results, vision, hearing, language, weight, height, and behavior were
      evaluated. RESULTS: At the last evaluation, 37% of children were completely
      normal (24% had always been normal); 52% were normal in the 4th year of life,
      decreasing to 31% in the 8th year. Minor disabilities increased from 31% in the
      4th year to 53% in the 8th year. Moderate disabilities ranged yearly between 8
      and 14%. Five children had major handicaps diagnosed before 3 years of age (4
      cerebral palsies following severe neonatal brain lesions and 1 severe retardation
      with renal dwarfism). No difference was found between children with or without
      bronchopulmonary dysplasia. Twelve children (14%) had hearing loss (3 deafness)
      and 27 (32%) had visual deficits (no blindness). Nursery school begins at 3 for
      French children: 86% of the followed survivors were at nursery school at 3 years
      of age, 74% of 6-year-olds were in the first grade, primary school, and 50% of 7
      year-olds were in second grade. Half the children with high
      socioeconomic/cultural risks had some school difficulties. Similar results were
      collected from various cross-sectional studies in the recent literature.
      CONCLUSIONS: While 20% of the children had moderate to severe disabilities, an
      increasing number of minor deficiencies appeared with age. Socio
      economic/cultural factors had a deleterious effect even in structurally normal
      children, but they had an even worse effect in children with minor deficiencies,
      owing largely to the frequent lack of proper management at home.

PMID- 9001695
TI  - Effects of colostrum feeding on intestinal development in newborn pigs.
AB  - To investigate what factors lead to rapid postnatal tissue growth and functional
      maturation in the newborn intestine, we compared intestinal tissue mass and
      digestive enzyme activities between newborn unsuckled piglets and piglets bottle
      fed for 3 days with either 5% lactose solution, intact porcine colostrum or
      trypsinized porcine colostrum. Bottle feeding of colostrum or trypsinized
      colostrum, but not lactose solution, led to a significant increase in the weight
      and length of the small intestine (p < 0.01) and a significant increase in the
      mucosal weight of the large intestine (p < 0.05). The mucosal protein content in
      the small and large intestine and the mucosal DNA content in the large intestine
      increased significantly following 3 days of bottle feeding of porcine colostrum
      or trypsinized colostrum. The total mucosal DNA contents in the small intestine
      of piglets fed colostrum or trypsinized colostrum were, respectively, 39 and 64%
      greater than that in the newborn unsuckled piglets. Intestinal digestive enzymes
      showed a differential response to the dietary treatment. Bottle feeding of intact
      porcine colostrum, but not trypsinized porcine colostrum led to a significant
      increase in lactase- and alkaline phosphatase-specific activities in the small
      intestine, while bottle feeding of lactose solution led to a significant decrease
      in the specific activity of lactase. In contrast, the specific activity of
      maltase in the small intestine increased significantly with age irrespective of
      dietary treatment. These results indicate that genetic and dietary factors are
      involved in regulating postnatal intestinal development, and porcine colostrum
      contains a trypsin-labile component which can increase lactase and alkaline
      phosphatase activities in the newborn intestine.

PMID- 9001696
TI  - Microvascular pressures in isolated perfused immature lamb lungs: effects of flow
      rate, left atrial pressure and surfactant therapy.
AB  - To determine the effect of some physical factors on microvascular pressures in
      immature lungs, we studied the lungs of 125-day gestation immature lambs (term
      150 days). Lambs were delivered and ventilated for 30 min prior to isolation of
      the lungs. Nine had surfactant (Survanta, 100 mg/kg) instilled into the lungs
      prior to delivery, and 7 did not (control group). Lungs were kept distended with
      airway pressure at 20 cm H2O and perfused with autologous blood, using a steady
      flow pump. Papaverine was added to the blood to eliminate vasomotion. We measured
      pulmonary artery and arterial, double and venous occlusion pressures, with flow
      at 100, 200 and 260 ml.kg-1.min-1 and left atrial pressure (Pla) at 0, 10 and 15
      mm Hg. We found that the vascular pressure profile was similar in control and
      surfactant-treated lungs under similar conditions of flow and Pla. Our data show
      that elevation of Pla results in significant increases in capillary (double
      occlusion) pressure; however, the preterm lung accommodates increases in flow
      with little change in capillary pressure. An increase in flow rate in the
      presence of elevated Pla had the greatest effect on capillary pressure. All lungs
      became hemorrhagic when capillary pressure exceeded 30 mm Hg. We speculate that
      in preterm infants, stress failure of pulmonary capillaries and hemorrhage will
      occur when there is marked elevation of capillary pressures resulting from
      increased blood flow in the presence of pulmonary venous construction or left
      ventricular dysfunction.

PMID- 9001697
TI  - Improved recovery from laryngeal-stimulation-induced apnea by alpha-adrenergic
      blockade in adult rabbits.
AB  - The apnea triggered by laryngeal stimulation (LS) is associated with a
      redistribution of blood flow towards the heart and the brain that depends upon
      peripheral vasoconstriction. The circulatory component of the response to LS has
      been shown to be reduced following injection of large dose of beta-adrenergic
      agonist that more intriguingly blunted the ventilatory response as well. To test
      whether the reduction of LS-induced apnea could be related to the decreased
      magnitude of the peripheral vasoconstruction, the effects of the alpha-adrenergic
      antagonist urapidil on the ventilatory and blood pressure responses to LS were
      studied in 6 adult rabbits. alpha-Adrenergic blockade reduced both the rise in
      blood pressure and the magnitude of hypopnea induced by LS. These results suggest
      that the circulatory component of the laryngeal chemoreflex, i.e. the peripheral
      vasoconstruction, contributes to the magnitude of the ventilatory depression.

PMID- 9001699
TI  - Opioid antagonists in the periaqueductal gray inhibit morphine and beta-endorphin
      analgesia elicited from the amygdala of rats.
AB  - In addition to brainstem sites of action, analgesia can be elicited following
      amygdala microinjections of morphine and mu-selective opioid agonists. The
      present study examined whether opioid analgesia elicited by either morphine or
      beta-endorphin in the amygdala could be altered by either the general opioid
      antagonist, naltrexone, the mu-selective antagonist, beta-funaltrexamine (BFNA)
      or the delta 2 antagonist, naltrindole isothiocyanate (Ntii) in the
      periaqueductal gray (PAG). Both morphine (2.5-5 micrograms) and beta-endorphin
      (2.5-5 micrograms) microinjected into either the baso-lateral or central nuclei
      of the amygdala significantly increased tail-flick latencies and jump thresholds
      in rats. The increases were far more pronounced on the jump test than on the tail
      flick test. Placements dorsal and medial to the amygdala were ineffective.
      Naltrexone (1-5 micrograms) in the PAG significantly reduced both morphine (tail
      flick: 70-75%; jump: 60-81%) and beta-endorphin (tail-flick: 100%; jump: 93%)
      analgesia elicited from the amygdala, indicating that an opioid synapse in the
      PAG was integral for the full expression of analgesia elicited from the amygdala
      by both agonists. Both BFNA (68%) and Ntii (100%) in the PAG significantly
      reduced morphine, but not beta-endorphin analgesia in the amygdala on the tail
      flick test. Ntii in the PAG was more effective in reducing morphine (60%) and
      beta-endorphin (79%) analgesia in the amygdala on the jump test than BFNA (15
      24%). Opioid agonist-induced analgesia in the amygdala was unaffected by opioid
      antagonists administered into control misplacements in the lateral mesencephalon,
      and the small hyperalgesia elicited by opioid antagonists in the PAG could not
      account for the reductions in opioid agonist effects in the amygdala. These data
      indicate that PAG delta 2, and to a lesser degree, mu opioid receptors are
      necessary for the full expression of morphine and beta-endorphin analgesia
      elicited from the amygdala.

PMID- 9001698
TI  - A TTX-sensitive conductance underlying burst firing in isolated pyramidal neurons
      from rat neocortex.
AB  - Pyramidal neurons were acutely isolated from neocortex slices of 14- to 20-day
      old rats and patch-clamped under physiological conditions. Current-clamp
      recordings revealed firing patterns corresponding to those previously reported in
      slices as regular spiking (RS) and intrinsically bursting (IB), i.e., single
      action potentials (AP), trains of regular spikes and bursts with depolarizing
      after-potentials (DAP). In IB neurons, intracellular perfusion with KF blocked
      the high-voltage-activated Ca2+ and the Ca(2+)-dependent K+ currents, revealing
      APs with a 10-30 ms shoulder at -35 mV (shoulder AP), which was the supporting
      plateau of the intraburst spikes. The use of the A channel blocker, 4
      aminopyridine, caused a three-fold reduction in the AP repolarizing rate. A study
      of the de- and repolarizing rates modulating the spike shape (shoulder AP, burst
      or single APs) suggested that the percentage of available A channels could play a
      crucial role in burst formation. Blockade of the residual T-type Ca2+ current by
      Ni2+ did not inhibit the AP shoulder, whereas it was completely and reversibly
      inhibited by 30 nM TTX, which did not affect AP amplitude. The AP rising rate was
      only halved by 100 nM TTX. The data concerning the A channel-mediated burst
      formation and the role of the TTX-sensitive conductance have been successfully
      simulated in a model cell. We suggest that bursting is an intrinsic property of
      the membrane of neocortex neurons, and is sustained by TTX-sensitive slowly
      inactivating and/or persistent Na+ conductances.

PMID- 9001700
TI  - Rapid conversion of myelin-associated glycoprotein to a soluble derivative in
      primates.
AB  - Myelin-associated glycoprotein (MAG) is susceptible to proteolysis by a calcium
      activated neutral protease which is located in myelin. The conversion of MAG
      (M(r) 100,000) to its soluble derivative dMAG (M(r) 90,000) occurs much more
      rapidly in myelin from human white matter than in myelin from rat brain, and the
      rate of formation of dMAG is increased even more in myelin from white matter of
      patients with multiple sclerosis (MS). The MAG to dMAG conversion was studied in
      several species, ranging from mice to non-human primates and humans to determine
      what animal model would be the most appropriate for investigating the MAG to dMAG
      reaction in demyelinating disorders. Myelin fractions from brains of these
      species were prepared and incubated at 37 degrees C in 0.2 M NH4HCO3, pH 7.4 for
      time periods ranging from 5 min to 24 h. Western blot analysis of the samples,
      taken at the end points of the different incubation periods, showed that the time
      required for a 50% conversion of MAG to dMAG was 18-24 h in myelin from rodents
      to bovine. The non-human primate studies revealed a 50% conversion at 2 h for
      marmoset samples and rhesus monkey samples, 20 min for gorilla samples and 10 min
      for chimpanzee samples. Human myelin samples needed only 5 min for a 50%
      conversion of MAG to dMAG. The reason for the significantly faster formation of
      dMAG in primate myelin is unknown and currently is being investigated.

PMID- 9001701
TI  - Centrally infused galanin-(1-15) but not galanin-(1-29) reduces the baroreceptor
      reflex sensitivity in the rat.
AB  - It has been demonstrated previously that central administration of the N-terminal
      galanin fragment (1-15) elicits hypertension and tachycardia and antagonizes the
      hypotensive effect of the parent molecule galanin-(1-29). In order to further
      clarify the role of galanin in central cardiovascular control, the possible
      modulation of the baroreceptor reflex by both galanin molecules has been studied.
      Different groups of rats were injected in the lateral ventricle with subthreshold
      doses of galanin-(1-15) (0.1 nmol/rat, or 0.3 nmol/rat), with subthreshold doses
      of galanin-(1-29) (0.1 nmol/rat, and 0.3 nmol/rat) or with an effective dose of
      galanin-(1-29) (3.0 nmol/rat). The baroreceptor reflex was elicited by
      intravenous injections of different doses of L-phenylephrine before and after the
      intraventricular administration of galanin peptides. The changes of the
      bradycardic responses after galanin peptide injections as well as the
      modifications of the baroreceptor reflex sensitivity were evaluated.
      Intraventricular injections of galanin-(1-15) significantly inhibited the reflex
      bradycardia elicited by intravenous L-phenylephrine and thus decreased the
      baroreceptor sensitivity. However, neither subthreshold doses of galanin-(1-29)
      nor its effective dose were able to modulate these cardiovascular responses. From
      these data it may be suggested that the galanin fragment (1-15) plays a more
      important role in central cardiovascular regulation than galanin-(1-29), possibly
      acting on a specific receptor subtype which exclusively recognizes N-terminal
      fragments of galanin, and exists on cardiovascular areas of the central nervous
      system.

PMID- 9001702
TI  - Dendritic shrinkage and dye-coupling between rat hippocampal CA1 pyramidal cells
      in the tetanus toxin model of epilepsy.
AB  - A small dose of tetanus toxin injected into the rat hippocampus produces a
      chronic model of temporal lobe epilepsy. We have examined whether morphological
      changes occur in hippocampal CA1 pyramidal cells in this model by using
      intracellular injections of biocytin. Eight weeks after the injection of tetanus
      toxin, significantly more "dye-coupled' cells were found in this group than in
      the buffer (control) injected group (63% compared with 7%). Half of these coupled
      cells appeared to be linked at the soma, and the other half by dendrodendritic
      contacts. Analysis of the dendritic trees revealed that the tetanus toxin group
      showed a decrease in complexity around the proximal to mid-apical dendritic
      regions and around the mid- to distal basal dendritic regions. The dye-coupling
      indicates that electrotonic interaction is induced or strengthened between
      hippocampal neurones, possibly as a result of the epilepsy-induced dendritic
      damage.

PMID- 9001703
TI  - Characterization of epileptiform field potentials recorded in the in vitro
      perirhinal cortex of amygdala-kindled epileptogenesis.
AB  - The perirhinal cortex (PRC) has recently been reported that the excitatory role
      of this area is important for the generation and the propagation of kindled
      seizures. In the present study, we investigated the extracellular
      electrophysiological properties of the circuitry which contribute to the
      propagation of seizures in the PRC, and examined the hypothesis that amygdala
      kindling changes the electrophysiological nature of the rat PRC slice in vitro.
      Field potentials elicited in the PRC had extended duration (> 200 ms, most
      approximately equal to 1 s) with overlying spike components. The potentials
      showed strong synchronizing effect governed by an all-or-none rule. Although
      spontaneous epileptiform discharges that were equivalent in appearance to
      synaptically-activated field potentials were observed in the PRC of both amygdala
      kindled and control rats, the number of slices showing spontaneous activity was
      significantly larger in the kindled group than in the control group (chi 2-test,
      P < 0.01). The occurrence of tetanus-induced afterdischarges in kindled rats was
      significantly higher than in control rats (chi 2-test, P < 0.01). The
      afterdischarge durations of control slices were generally short and the
      afterdischarges did not consist of the typical "tonic-clonic' phases. However,
      the occurrence of the electrographical seizure in the high K+ ACSF were not
      affected by amygdala-kindling operation. These results indicate that amygdala
      kindling lowers the threshold for transsynaptic excitability and enhances the
      synchronized activity of the PRC induced by episodic proconvulsive manipulations
      such as tetanus stimulation.

PMID- 9001704
TI  - Comparison of the developmental effects of two mercury compounds on glial cells
      and neurons in aggregate cultures of rat telencephalon.
AB  - A three-dimensional cell culture system was used as a model to study the
      influence of low levels of mercury in the developing brain. Aggregating cell
      cultures of fetal rat telencephalon were treated for 10 days either during an
      early developmental period (i.e., between days 5 and 15 in vitro) or during a
      phase of advanced maturation (i.e., between days 25 and 35) with mercury. An
      inorganic (HgCl2) and an organic mercury compound (monomethylmercury chloride,
      MeHgCl) were examined. By monitoring changes in cell type-specific enzymes
      activities, the concentration-dependent toxicity of the compounds was determined.
      In immature cultures, a general cytotoxicity was observed at 10(-6) M for both
      mercury compounds. In these cultures, HgCl2 appeared somewhat more toxic than
      MeHgCl. However, no appreciable demethylation of MeHgCl could be detected,
      indicating similar toxic potencies for both mercury compounds. In highly
      differentiated cultures, by contrast, MeHgCl exhibited a higher toxic potency
      than HgCl2. In addition, at 10(-6) M, MeHgCl showed pronounced neuron-specific
      toxicity. Below the cytotoxic concentrations, distinct glia-specific reactions
      could be observed with both mercury compounds. An increase in the
      immunoreactivity for glial fibrillary acidic protein, typical for gliosis, could
      be observed at concentrations between 10(-9) M and 10(-7) M in immature cultures,
      and between 10(-8) M and 3 x 10(-5) M in highly differentiated cultures. A
      conspicuous increase in the number and clustering of GSI-B4 lectin-binding cells,
      indicating a microglial response, was found at concentrations between 10(-10) M
      and 10(-7) M. These development-dependent and cell type-specific effects may
      reflect the pathogenic potential of long-term exposure to subclinical doses of
      mercury.

PMID- 9001705
TI  - Effects of nitric oxide on stimulated release of norepinephrine from female rat
      hypothalamic slices.
AB  - Norepinephrine (NE) is an important neurotransmitter involved in ovarian steroid
      hormone regulation of female reproductive function in rats. Nitric oxide (NO) has
      also been suggested to be an essential mediator of gonadotropin-releasing hormone
      release and of lordosis behavior of female rats. These studies used a superfusion
      system to investigate the hypothesis that NO regulates [3H]NE release in the
      preoptic area (POA) and hypothalamus (HYP), brain regions that mediate ovarian
      steroid effects on reproductive function. The NO synthase inhibitors N-nitro-L
      arginine and NG-nitro-L-arginine methyl ester did not modify either basal or N
      methyl-D-aspartate (NMDA)-stimulated NE release in either brain region of
      ovariectomized, hormone-treated or control animals. The NO precursor L-arginine
      (L-Arg) reduced NMDA-stimulated NE release in POA but had no effect on KCl- or
      electrically-stimulated release. L-Arg did not influence basal or evoked release
      of [3H]NE from HYP slices. Sodium nitroprusside (SNP), a NO-generating compound,
      blocked the release of NE in response to NMDA stimulation but not in response to
      KCl or electrical stimulation. Thus, SNP is probably reducing NE release by
      acting as an NMDA antagonist rather than via NO production. There was a tendency
      for administration of both estrogen and progesterone to ovariectomized females to
      facilitate NMDA-stimulated NE release, particularly in the POA. Our data suggest
      that NO does not mediate basal or NMDA-stimulated NE release in rat POA and HYP.
      Therefore, NO regulation of lordosis behavior and gonadotropin release in female
      rats is probably not exerted at the level of NE release.

PMID- 9001706
TI  - L-deprenyl fails to protect mesencephalic dopamine neurons and PC12 cells from
      the neurotoxic effect of 1-methyl-4-phenylpyridinium ion.
AB  - L-Deprenyl, a monoamine oxidase (MAO)-B inhibitor, appears to slow down the
      progression of Parkinson's disease. While inhibition of MAO-B activity can
      account for some of the effects of this substance, the basis by which L-deprenyl
      slows the progression of the disease remains controversial. In recent years, a
      new mechanism of action has emerged that may explain the ability of L-deprenyl to
      increase neuronal survival. L-deprenyl has been reported to modify gene
      expression and protein synthesis in astrocytes and PC12 cells. In this study, we
      tested the ability of L-deprenyl to protect mouse mesencephalic cells from the
      toxicity of the 1-methyl-4-phenyl pyridinium ion (MPP+). We exposed mouse
      mesencephalic cell cultures to L-deprenyl (10 microM) and, 24 h later, to MPP+
      (2.5 microM). On the fifth day after L-deprenyl and MPP+ exposition, cells were
      washed free of drugs, and the following day they were tested for dopamine uptake,
      intracellular dopamine content and tyrosine hydroxylase immunoreactivity. The
      experiments were performed either in the presence or in the absence of glia. It
      was found that L-deprenyl pretreatment failed to achieve any protection against
      MPP+ toxicity. The fall in dopamine uptake and intracellular dopamine content,
      and the diminution of tyrosine hydroxylase immunoreactivity observed in cells
      pretreated with L-deprenyl and then given MPP+ were not significantly different
      from the values observed in cells treated with MPP+ alone. Additional experiments
      performed in PC12 cells, confirmed the failure of L-deprenyl to abolish the
      toxicity of MPP+. Our data seem to be at variance with previous reports
      demonstrating that the MAO-B inhibitor L-deprenyl protects dopaminergic neurons
      against MPP+ toxicity [12,20]; furthermore they do not support alternative
      mechanisms of action of L-deprenyl against MPP+ toxicity.

PMID- 9001707
TI  - Cellular localisation of metabotropic glutamate receptors in the mammalian optic
      nerve: a mechanism for axon-glia communication.
AB  - It has been proposed that neurotransmitter signalling can occur between axons and
      glia in the mammalian optic nerve in the absence of synaptic specialisations, and
      that this may be glutamate mediated. Here, the cellular distribution of five
      metabotropic glutamate receptors (mGluR's 1a, 1b, 1c, 2/3 and 5) have been
      assessed in the rat optic pathway using specific antibodies. Positive
      immunoreactivity is found for mGluR2/3 and 5. Both are found in axons, although
      only mGluR5 is present in the majority of these. Strong immunoreactivity for
      mGluR2/3 is found in cells in the optic pathway and thalamus. The cellular
      morphology and distribution is consistent with their being astrocytes.
      Examination of brain sections stained for mGluR2/3 is consistent with this
      notion, with many cells having end-feet processes terminating on blood vessels or
      the pial surface. The axonal immunoreactivity could represent the presence of
      these receptors on axons, but it is more probable that the receptor protein
      synthesised in the ganglion cell soma is being transported to the cell terminal
      in sufficient concentration to be revealed by immunohistochemistry. The reason
      for the axon-astrocyte signalling is unclear, and may be associated with
      metabolic coupling. In development, communication between axons and glia mediates
      a range of functions including pathway selection and myelination. It is probable
      that in the adult this form of signalling underpins a range of functions that
      have yet to be described.

PMID- 9001708
TI  - Pituitary adenylate cyclase-activating polypeptide protects rat-cultured cortical
      neurons from glutamate-induced cytotoxicity.
AB  - We have investigated the effects of pituitary adenylate cyclase-activating
      polypeptide with 38 residues (PACAP38) on glutamate-induced neuronal cell death
      in rat-cultured cortical neurons. The rat-cultured neurons were obtained from E17
      day-old embryos and cultured in a chemically defined medium without serum for 10
      days, after which more than 95% of the cells were stained by a specific antibody
      against MAP-2, a specific marker for neurons. The number of viable neurons was
      identified by the mitochondrial conversion of 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) to formazan, which was detected by the
      associated change in optical density at 570 nm. Glutamate-induced neuronal cell
      death was suppressed by PACAP38 at concentrations as low as 10(-13) M, and at 10(
      11) M maximally suppressed half of the amount of glutamate-induced cell death
      seen in a control situation (no PACAP38). The dose-response curve was bell
      shaped. Dibutyryl cAMP (dbcAMP) also increased the number of neurons that were
      protected from damage with a bell-shaped dose-response curve suggesting that
      PACAP exerts its neuroprotective effect through the activation of a cAMP signal
      transduction system. However, cAMP accumulation in the media of neurons was
      stimulated by PACAP38 at concentrations as low as 10(-11) M, a much higher
      concentration than the minimal effective dose of PACAP38 required for protection
      against glutamate-induced neuronal cell death. Among the three neuropeptides of
      PACAP38, arginine vasopressin (AVP) and C-type natriuretic peptide (CNP), only
      PACAP38 exhibited a neurotrophic effect in the glutamate-induced neuronal cell
      death at the indicated concentrations. These data indicate that PACAP38 is one of
      the more important neuroprotective factors. The kind of intracellular signal
      transduction system involved in the neuroprotective effect of PACAP38 still
      remains to be established.

PMID- 9001709
TI  - Chronic amitriptyline exposure reduces 5-HT3 receptor-mediated cyclic GMP
      formation in NG 108-15 cells.
AB  - In the present study, we investigated the effects of chronic in vitro
      administration of amitriptyline, a tricyclic antidepressant, on cyclic GMP
      formation stimulated by 5-hydroxytryptamine (5-HT) in the neuroblastoma x glioma
      hybrid cell line, NG 108-15, 5-HT (0.01-100 microM)-stimulated cyclic GMP
      formation was concentration-dependent and was sensitive to ICS 205-930, a 5-HT3
      receptor antagonist. Exposure of NG 108-15 cells to 5 microM amitriptyline for 3
      days significantly reduced 5-HT-stimulated cyclic GMP formation. Acute treatment
      with amitriptyline had no effect on 5-HT-stimulated cyclic GMP formation. The
      reduction by chronic amitriptyline exposure of 10 microM 5-HT-stimulated cyclic
      GMP formation was concentration-dependent over the concentration range examined
      (0.5 to 10 microM). The IC50 of amitriptyline was 1.9 microM. In contrast,
      amitriptyline exposure, even at a concentration of 8 microM, failed to modify
      cyclic GMP formation stimulated by bradykinin, sodium nitroprusside, or atrial
      natriuretic peptide. Increases in intracellular Ca2+ concentration ([Ca2+]i)
      evoked by 10 microM 5-HT were attenuated in amitriptyline-exposed cells, while
      100 nM bradykinin-induced [Ca2+]i increases were not affected. In addition,
      chronic exposure to 5 microM amitriptyline caused a decrease in affinity (Kd) of
      [3H]zacopride specific binding to 5-HT3 recognition sites. The Bmax for the
      labelled ligand remained unchanged. These results suggest that chronic
      amitriptyline exposure reduces 5-HT-stimulated cyclic GMP formation and [Ca2+]i
      increases, and this may reflect the functional changes of 5-HT3 receptors.

PMID- 9001710
TI  - Inhibition of protein phosphatase-2B (calcineurin) activity towards Alzheimer
      abnormally phosphorylated tau by neuroleptics.
AB  - Abnormally hyperphosphorylated tau is the major protein component of
      neurofibrillary tangles, the characteristic lesion of Alzheimer's disease (AD).
      Protein phosphatases (PP) type 1 (PP-1), type 2A (PP-2A) and type 2B (PP-2B)
      appear to be involved in the regulation of tau phosphorylation. The incidence of
      neurofibrillary tangles is higher in brains of schizophrenic patients treated
      with neuroleptics than in those without this treatment. We have found that the
      commonly used neuroleptics chlorpromazine, trifluoperazine and clozapine inhibit
      PP-2B but not PP-1 or PP-2A activity towards [32P]phosphorylase kinase as a
      substrate. When AD abnormally hyperphosphorylated tau is used as a substrate, PP
      2B activity is inhibited by trifluoperazine > chlorpromazine > clozapine. Using
      phosphorylation-dependent monoclonal antibodies, tau-1, AT8 and PHF-1, we have
      found that the dephosphorylation of the abnormal tau by PP-2B is inhibited at all
      the sites recognized by these antibodies. The IC50 of the inhibition of
      dephosphorylation at tau-1 site is approximately 20 microM for trifluoperazine
      and approximately 120 microM for chlorpromazine. These two neuroleptics inhibit
      tau dephosphorylation by PP-2B through antagonizing calmodulin as well as
      directly interacting with PP-2B. The inhibition of the dephosphorylation of
      abnormally hyperphosphorylated tau by neuroleptics raises an intriguing
      possibility that the chronic use of these drugs might contribute to
      neurofibrillary degeneration in schizophrenic and AD patients.

PMID- 9001711
TI  - Complete recovery by nerve growth factor of neuropeptide content and function in
      capsaicin-impaired sensory neurons.
AB  - In the present study the ability of nerve growth factor (NGF) to facilitate the
      recovery of peptidergic primary sensory C-fibers after an acute capsaicin
      treatment (50 mg/kg s.c.) was investigated in adult rats. NGF (4 micrograms 1/day
      for 3 days) was injected into the plantar of one hind paw starting 24 h after the
      capsaicin treatment. Without NGF, there was a significant reduction of calcitonin
      gene-related peptide (CGRP) and substance P content of the paw skin and the
      sciatic nerve. CGRP and substance P levels were completely replenished in the NGF
      treated paw skin and in the innervating sciatic nerve they even increased over
      control levels as determined 40 h after the last injection of NGF. CGRP levels
      also recovered in the contralateral paw and sciatic nerve, but no recovery was
      observed in other tissues such as the front paw, the auricle, or the urinary
      bladder. Mustard oil-induced neurogenic plasma extravasation, taken as a
      functional parameter for peptidergic primary sensory C-fibers, was significantly
      decreased after the capsaicin treatment and showed a complete recovery by NGF in
      the injected paw as well as in the contralateral paw skin. These results show
      that NGF not only was able to reverse the decrease of transmitter content caused
      by capsaicin but also restored the peripheral function of primary afferent
      neurons.

PMID- 9001712
TI  - Forebrain contribution to the induction of a brainstem correlate of conditioned
      taste aversion: I. The amygdala.
AB  - The induction of c-Fos-like immunoreactivity (c-FLI) in the intermediate division
      of the nucleus of the solitary tract (iNTS) has been shown to be a reliable
      cellular correlate of the acquisition and/or behavioral expression of a
      conditioned taste aversion (CTA). To begin to define neuroanatomical structures
      and pathways that contribute to this cellular response and to CTA learning in
      general, electrolytic lesions of the amygdala were combined with immunostaining
      for c-FLI. Rats were given either unilateral or bilateral electrolytic lesions of
      the amygdala or "sham' operations. Following surgery "paired' animals were given
      a single conditioning trial consisting of intraoral infusion of 5 ml 0.15% sodium
      saccharin followed by injection with LiCl (0.15 M, 20 ml/kg, i.p.) while
      "unpaired' controls received a non-contingent saccharin-LiCl presentation. When
      tested, unilateral-lesioned rats displayed a CTA by rejecting the saccharin, but
      increases in c-FLI were evident only on the side of the iNTS contralateral to the
      lesion. Rats with bilateral lesions showed no evidence of having acquired a CTA
      and no increase in c-FLI in iNTS relative to unpaired controls. These findings
      support involvement of amygdala in CTA learning and suggest that a lateralized
      connection between amygdala and iNTS is necessary for the conditioned c-FLI which
      is induced by exposure to a conditioned aversive taste.

PMID- 9001713
TI  - Inhibition of sexual behaviour and the luteinizing hormone surge by intracerebral
      progesterone implants in the female sheep.
AB  - In female sheep, progesterone blocks the induction by oestradiol of both sexual
      behaviour and the pre-ovulatory surges of gonadotrophin releasing hormone (GnRH)
      and luteinising hormone (LH). However, the central sites of action of
      progesterone remain poorly defined, so we attempted to locate them by implanting
      progesterone intracerebrally in ovariectomised ewes treated with exogenous
      steroids to induce oestrous behaviour and the LH surge. Single bilateral implants
      or a double bilateral implants filled with progesterone or cholesterol were
      placed in the ventromedial hypothalamus (VMH) or the preoptic area (POA). Control
      ewes were not implanted. To determine the inhibitory capacity of the central
      progesterone implants, ewes received an injection (i.m.) of 8 micrograms or 16
      micrograms of oestradiol. The single bilateral implants of progesterone failed to
      block oestrous behaviour and the LH surge induced by 8 micrograms of oestradiol.
      Double bilateral progesterone implants in the VMH blocked the sexual behaviour (P
      < 0.05) and the LH surge (P < 0.05), but implants in the POA blocked only sexual
      receptivity (P < 0.05). No changes were observed after central implantation of
      cholesterol. Our results support the hypothesis that progesterone acts centrally
      in the VMH and the POA to inhibit the induction of LH surge and sexual behaviour
      by oestradiol.

PMID- 9001714
TI  - Calretinin mRNA and immunoreactivity in the medullary reticular formation of the
      rat: colocalization with glutamate receptors.
AB  - Calretinin-positive cells were identified in the medullary reticular formation of
      the rat by both immunohistochemistry and in situ hybridization histochemistry. In
      addition, double immunocytochemical labeling was used to examine the degree of
      colocalization of calretinin with GluR2/R3, GluR4 and GluR5-7 glutamate receptor
      subtypes. Results indicated regional variation in calretinin expression across
      reticular formation regions with the exception of the largest cells which were
      mostly calretinin-positive. Calretinin mRNA was particularly abundant in the
      parvocellular reticular nucleus. Most calretinin-immunoreactive cells also
      expressed at least one of the glutamate receptor subtypes examined with the
      exception of the smallest calretinin-positive cells of the parvocellular
      reticular formation which were generally not immunoreactive for any of the
      glutamate receptors examined. Calretinin immunoreactivity was colocalized with
      immunoreactivity for all three glutamate receptor subtypes examined in most of
      the large cells of the reticular formation. Immunoreactivity for the GluR4
      antibody was least abundant in the reticular formation and GluR4 immunoreactive
      cells were least likely to co-express calretinin. These results suggest that
      calretinin and glutamate receptor antibodies may be used to identify specific
      subsets of reticular formation neurons.

PMID- 9001715
TI  - Neuronal cytotoxicity of inositol hexakisphosphate (phytate) in the rat
      hippocampus.
AB  - D-myo-Inositol hexakisphosphate (InsP6, phytate), a normal cellular constituent,
      was found to be toxic to neuronal perikarya when injected into the rat
      hippocampus. However, the extrinsic cholinergic innervation of the hippocampus
      (as estimated by staining for acetylcholinesterase) was unaffected. Its potency
      as a toxin was approximately equal to that of the excitotoxin quinolinate. Other
      highly charged derivatives of inositol (inositol hexakissulphate, inositol
      monophosphate) were not toxic. The cytotoxicity of InsP6 was not due to a high
      osmolality, or to seizure-induced lesions, but was reduced by calcium.
      Nevertheless, the toxicity was not due to chelation of brain calcium by InsP6, as
      another calcium chelator with a higher affinity for calcium, 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), produced only a very mild
      lesion. Thus, abnormal metabolism of InsP6 might possibly contribute to neuronal
      death in neurodegenerative diseases.

PMID- 9001717
TI  - Dextromethorphan reduces functional deficits and neuronal damage after global
      ischemia in rats.
AB  - Glutamate antagonists have been shown to be neuroprotective in animal models of
      cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal
      damage in the hippocampus and striatum. Following ischemia a transient locomotor
      hyperactivity and a deficit in spatial learning and memory occurs. The aim of the
      present study was to investigate the potential neuroprotective effect of
      dextromethorphan, an antagonist at the N-methyl-D-aspartate receptor, with
      behavioural and histological measures of global ischemia in rats. Global ischemia
      was induced by four-vessel occlusion (4VO) for 20 min in rats. Dextromethorphan
      was administered 20 min before induction of ischemia at a dose of 10 or 50 mg/kg.
      Before and on day 1, 3 and 5 after operation the spontaneous locomotor activity
      was measured. One week after surgery spatial learning was tested in the Morris
      water maze. After behavioural testing the animals were sacrificed and the
      neuronal damage was assessed. Treatment with 50 mg/kg of dextromethorphan reduced
      the increase in locomotor activity observed on day 1 and 3 after ischemia. In the
      water maze dextromethorphan reduced the increase in escape latency and in swim
      distance induced by 4VO. Furthermore, the ischemia-induced reduction in time
      spent in the quadrant of the former platform position during the probe trial was
      increased by treatment with dextromethorphan. Neuronal damage in the CA1 sector
      of the hippocampus and in the dorsolateral striatum produced by 4VO was
      significantly attenuated by dextromethorphan. The present results demonstrate
      that protective effects on neuronal damage may be related to an attenuation of
      deficits in spatial leaning and memory following global ischemia.

PMID- 9001716
TI  - A post mortem study on neurochemical markers of dopaminergic, GABA-ergic and
      glutamatergic neurons in basal ganglia-thalamocortical circuits in Parkinson
      syndrome.
AB  - Functional models of the circuitry of the basal ganglia have recently been
      proposed to account for the vast spectrum of motor disorders associated with the
      loss of anatomical or neurochemical integrity within the basal ganglia. On the
      basis of these hypothetical models, hypokinetic disorders such as Parkinson's
      disease, are thought to be associated with excessive tonic and phasic inhibition
      of the output from the basal ganglia to the thalamus. In the present study we
      have attempted to determine the validity of the proposed model by measuring
      neurochemical markers of inhibitory and excitatory neurotransmission in post
      mortem human brain tissue. We have determined the concentrations of the
      excitatory neurotransmitters aspartate/glutamate and of the inhibitory
      neurotransmitter GABA in 18 relevant regions of the thalamocortical circuits of
      the basal ganglia of patients who had manifested Parkinsonian symptoms, and
      compared them with controls of individuals who had died without any history of
      neurological or psychiatric disorders and had no neuropathological abnormalities.
      Additionally, the receptor subtype for the excitatory amino acid N-methyl-D
      aspartate (NMDA) was studied in the same brain tissue in which neurotransmitter
      concentrations had been analysed as neurochemical markers of post-synaptic
      excitatory neurotransmission. In patients who had manifested Parkinsonian
      symptoms, glutamate and aspartate levels were found to be unchanged in all
      examined brain regions. In contrast, the binding of [3H]MK-801, which identifies
      the NMDA receptor, was reduced in the head (-42%) and body (-38%) of the caudate
      nucleus. In parkinsonian patients, GABA levels were diminished by 36% in the
      centromedial thalamus, compared to control values. These results do not confirm
      the changes in neurotransmitter concentrations predicted according to the model,
      although we cannot rule out that the predicted changes might have been observed
      if the Parkinsonian group had been further subdivided into groups diagnosed on
      the basis of the patients' clinical picture (akinetic-rigid, tremor-dominant,
      equivalent type) and compared with the control group.

PMID- 9001718
TI  - The effects of induced apneic episodes on cerebral cortical oxygenation in
      newborn piglets.
AB  - The effect of different inspiratory oxygen levels (FiO2) on cortical oxygenation
      (pO2) during and after recovery from apnea, was investigated in 18 anesthetized,
      paralyzed, and mechanically ventilated newborn piglets. Heart rate (HR) and mean
      arterial blood pressure (MABP) were continuously monitored as the piglets were
      subjected to repeated episodes of apnea initiated by disconnecting the ventilator
      and terminated when HR decreased to less than 80 beats/min by reconnecting the
      ventilator. A closed cranial window was placed over the parietal cortex of the
      animals and cortical pO2 was measured optically by phosphorescence quenching.
      Apneic episodes induced in animals ventilated with 15%, 22% and 40% oxygen had
      mean duration's of apnea (time before HR decreased to less than 80 beats/min) of
      80, 128 and 134 s, respectively. By the end of the apnea the MABP decreased to
      82%, 64%, and 54% of control, respectively. The cortical pO2 decreased from
      control values of 24.1, 32.3 and 38.3 Torr at 15%, 22% and 40% oxygen,
      respectively, to 1.7 to 3.2 Torr at the end of the apneic episode. The duration
      of apnea necessary for the cortical pO2 to drop below 20.3 Torr was 18, 44 and 81
      s at 15%, 22% and 40% oxygen, respectively. There was an inverse correlation
      between the rate of decline of cortical pO2 and baseline FiO2 levels. With
      reventilation, the cortical pO2 reached maximal values of 42.8, 51.9 and 57.2
      Torr at 15%, 22%, and 40% oxygen, respectively, before returning to the pre-apnea
      values. The present results show that apnea of less than 30 s duration at an FiO2
      of 22% do not result in significant cortical hypoxia in hemodynamically stable
      piglets. Increasing the FiO2 to above 22% may possibly increase the rate of
      recovery of tissue oxygenation but it also may facilitate post-hypoxic cortical
      hyperoxia, a factor that may predispose the immature brain to free radical
      injury.

PMID- 9001719
TI  - Characterization of L-alpha-aminoadipic acid transport in cultured rat
      astrocytes.
AB  - The mechanism of the selective gliotoxicity of L-alpha-aminoadipate (L-alpha AA)
      is thought to involve its entry into glia as a substrate for glutamate
      transporters or, alternatively, its ability to inhibit glial glutamate transport.
      To clarify the properties of L-alpha AA as a transport substrate, we explored the
      ionic dependence, kinetics and pharmacology of L-[3H] alpha AA uptake in rat
      cortical astrocytes. We observed two components of saturable L-alpha AA uptake,
      one Na(+)-dependent and the other Na(+)-independent. These components exhibited
      the characteristics of system X-AG, the widespread family of Na(+)-cotransporters
      of aspartate and glutamate, and system x-c, a Cl(-)-dependent glutamate/cystine
      exchanger, respectively. The K(m) value of Na(+)-dependent L-alpha AA uptake was
      629 +/- 42 microM, and Vmax was 62 +/- 4 nmol.min-1.mg-1 protein, which was more
      than twice the capacity of Na(+)-dependent glutamate uptake. The kinetic
      parameters of Na(+)-dependent L-alpha AA uptake (K(m) of 20 +/- 2 microM, Vmax of
      1.7 +/- 0.4 nmol.min-1.mg-1 protein did not differ from the values for Na(+)
      independent glutamate uptake, indicating that L-alpha AA and glutamate are
      equally good substrates for system x-c.

PMID- 9001720
TI  - Anoxic terminal negative DC-shift in human neocortical slices in vitro.
AB  - In animal models, the hallmark of a hypoxic condition is a strong negative shift
      of the DC potential (anoxic terminal negativity, ATN). This DC-shift is
      interpreted to be primarily due to a breakdown of the membrane potential of
      neurons. Such massive neuronal depolarizations have not been reported for all
      human neocortical neurons in vitro even during prolonged hypoxic periods. This
      poses the question whether ATN develop also in human neocortical slices made
      hypoxic. ATN could be observed when human brain slice preparations (n = 15, 13
      patients) were subjected to periods of hypoxia (10 to 120 min). These ATN were
      usually monophasic and appeared with a latency of 16 +/- 4 min (mean +/- S.E.M.).
      Separating the ATN according to their slopes of rise, steep (> 10 mV/min) and
      flat (< 10 mV/min) ATN could be distinguished. Steep and flat ATN may be regarded
      as two different entities of reactions since steep ATN had also greater
      amplitudes and slopes of decay as compared a flat ATN. With repetitive hypoxias,
      the latency of both the steep and flat ATN was reduced for the following hypoxic
      episodes. During hypoxic DC-shifts, evoked potentials were suppressed. With the
      1st through 4th hypoxia, they recovered fully within 30 min after reoxygenation
      when hypoxia was terminated at the plateau of ATN; with extension of hypoxia,
      recovery was only partial. From the 5th hypoxia onwards, recovery usually did not
      take place or was not complete.

PMID- 9001721
TI  - Distribution of phosphoneuroprotein 14 (PNP 14) in vertebrates: its levels as
      determined by enzyme immunoassay.
AB  - We have established an enzyme immunoassay for phosphoneuroprotein 14 (PNP 14)
      which is mainly localized in the cytoplasmic matrix in presynaptic axon terminals
      and which is phosphorylated in vivo, as well as in vitro. Fab' prepared from
      rabbit IgG antibodies against bovine PNP 14 was conjugated with maleimide
      horseradish peroxidase. The enzyme-conjugated Fab' was used as a second antibody
      in a sandwich enzyme immunoassay. This assay was able accurately to quantify 0.5
      100 ng of rat PNP 14, as well as bovine PNP 14, and it was used for the
      determination of concentrations of PNP 14 in various rat tissues, neuroblastoma
      cells, and brains of other vertebrates. The concentrations of PNP 14 in the rat
      cerebrum, cerebellum, and testis were 1.1, 1.0, and 0.28 micrograms/mg of
      protein, respectively, and those in other tissues examined were less than 0.1
      microgram/mg of protein. PNP 14 was also found in cultured cells, such as rat
      pheochromocytoma PC12 cells, NG108-15 cells, which are a hybrid between a mouse
      neuroblastoma and a rat glioma, mouse neuroblastoma Neuro-2a cells, and human
      neuroblastoma IMR32 cells. Furthermore, PNP 14-specific immunoreactivity was
      evaluated in the brains of various vertebrates, such as fish, frog, snake and
      chicken by immunoblot and enzyme immunoassay. The results revealed the
      immunoreactivity in the brains of all vertebrates examined and the levels were
      determined to be 0.6-2.1 micrograms bovine PNP 14 equivalents per mg of protein,
      suggesting that PNP 14 might be an essential component of the central nervous
      systems of vertebrates.

PMID- 9001722
TI  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in non-human
      primates is antagonized by pretreatment with nimodipine at the nigral, but not at
      the striatal level.
AB  - The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown
      to induce parkinsonism in man and non-human primates. Hypotheses concerning the
      mechanism of action of MPTP have been related to the pathogenesis of nigral cell
      death in Parkinson's disease. For instance, alterations of calcium influxes have
      been reported to be implicated in both MPTP-induced parkinsonism and Parkinson's
      disease. Recently, we reported that nimodipine, a blocker of L-type calcium
      channels, prevents dopaminergic MPTP-induced neurotoxicity in C57B1/6 black mice.
      The present study extended these rodent findings to the non-human primate model
      of Parkinson's disease and assessed the effects of nimodipine, continuously
      applied by pellet for 18 days, on behavioural, biochemical and histological
      parameters, following systemic application of MPTP in common marmosets
      (Callithrix jacchus). The experimental design involved five groups of common
      marmosets and a total of 24 animals. Monkeys assigned to group I (n = 4) received
      subcutaneously implanted vehicle pellets 7 days prior to subcutaneous saline
      injections (control). Monkeys of group II (n = 4) were treated with nimodipine
      pellets (80 mg) and saline injections. Marmosets in group III (n = 8) were
      treated with vehicle pellets and received 4 times MPTP (MPTP-HCl, 2 mg/kg body
      weight subcutaneously, separated by an interval of 24 h for a total of 4 days).
      Monkeys in group IV (n = 4) and V (n = 4) were treated as group-III animals
      except for the implantation of nimodipine pellets (80 mg and 120 mg,
      respectively) 7 days prior to toxin exposure. In common marmosets MPTP induced
      severe parkinsonian symptoms, a pronounced dopamine depletion in the caudate
      putamen (more than 99% of control) and a loss of tyrosine hydroxylase
      immunoreactive cells in the substantia nigra (50% percent of control) 7 days
      after MPTP-administration. Pretreatment with nimodipine (120 mg pellets) did
      neither attenuate the behavioural impairments in MPTP-treated animals nor
      antagonize the striatal neurotoxin-induced dopamine depletion, but almost
      completely prevented (in a dose-dependent manner) the MPTP-induced decrease of
      nigral tyrosine hydroxylase immunoreactive cells. These data suggest that
      application of nimodipine, during the observation period of 7 days, protects
      against MPTP-induced neurotoxicity in common marmosets at the cellular nigral
      level, but not at the synaptic striatal level, implicating differential
      mechanisms of actions of MPTP-induced neurotoxicity at the nigral versus the
      striatal level.

PMID- 9001723
TI  - Immunoreactivity of growth inhibitory factor in normal rat brain and after stab
      wounds--an immunocytochemical study using confocal laser scan microscope.
AB  - The growth inhibitor factor (GIF) is a new member of the metallothionein family
      that is downregulated in Alzheimer's disease brain. Using a confocal laser scan
      microscope with polyclonal and monoclonal antibodies to GIF, and monoclonal
      antibodies to glial fibrillary acidic protein (GFAP) and MAP-2, we demonstrated
      that GIF immunoreactivity was expressed primarily in astrocytes and much less in
      neurons. In astrocytes of normal rat brain GIF immunoreactivity was detected
      mainly in the cell bodies, while GFAP immunoreactivity was detected mainly in the
      processes. GIF immunoreactivity was more strongly expressed in reactive
      astrocytes. These findings were confirmed with both polyclonal and monoclonal
      antibodies. Following stab wounds, a number of GIF-positive reactive astrocytes
      were detected around the wounds at 3 days postoperation. After 7 days GIF
      immunoreactivity was detected in cell bodies and processes of reactive
      astrocytes. The number of GIF-positive astrocytes and the intensity of the
      immunoreactivity remained elevated over the control levels at least through 28
      days. These immunocytochemical findings correlated well with changes in GIF
      protein and mRNA levels. Not only changes in GIF protein and mRNA levels but also
      intracellular localization of GIF in normal rat brain and after stab wounds in
      rat brain were different from those of GFAP. These results support the concept
      that GIF plays an important role in the processing of reconstruction after brain
      damage.

PMID- 9001724
TI  - Persistence of nonphotic phase shifts in hamsters after serotonin depletion in
      the suprachiasmatic nucleus.
AB  - Serotonin-containing fibres (5-HT) project from the raphe complex to the
      suprachiasmatic nucleus (SCN). Previous studies have suggested that this pathway
      may be involved in nonphotic resetting of the circadian clock. For example, 5-HT
      agonists are capable of phase shifting the biological clock both in vivo and in
      vitro, producing phase response curves (PRCs) similar in shape to those of other
      nonphotic stimuli. Therefore we studied the role of the serotonergic projection
      to the SCN in nonphotic phase shifts by bilateral injection of the selective 5-HT
      neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) onto the SCN of hamsters. About 50
      days after the administration of the neurotoxin, the 5-HT and 5-HIAA (5
      hydroxyindole acetic acid) levels were severely depleted in the SCN, as revealed
      by high performance liquid chromatography (HPLC), and immunocytochemistry (ICC).
      The average level of 5-HT depletion was 88% in Experiment 1 and 95% in Experiment
      2. This treatment had no effect on the magnitude of phase shifts produced by 3 h
      of novelty-induced wheel-running starting at circadian time (CT) 4, the peak of
      the advance region of the PRC to this stimulus. The effect of 5-HT depletion on
      shifts produced by running at CT 22 were inconclusive because of changes in the
      behavior of control animals. No changes in the phase angle of entrainment of
      animals in a 14:10 light:dark (LD) cycle were detected in depleted animals. The
      results suggest that the 5-HT projection from the raphe to the SCN is not
      essential for activity-induced phase shifts in hamsters.

PMID- 9001726
TI  - Role of catecholamines in the frontal cortex in the modulation of basal and
      stress-induced autonomic output in rats.
AB  - Exposure of animals to noxious or stressful stimuli increases heart rate (HR) and
      blood pressure through activation of the autonomic nervous system (ANS) and
      elicits the release of the catecholamines noradrenaline (NA) and dopamine (DA) in
      the frontal cortex. Subregions of the frontal cortex, such as the medial frontal
      cortex (MFC) and agranular insular cortex (AIC) project directly to brainstem
      nuclei involved in autonomic control. It may be hypothesized that catecholamines
      in the frontal cortex could influence autonomic output through actions on these
      descending pathways. To evaluate this hypothesis, the effects of intracortical
      microinjections of drugs acting at NAergic and DAergic receptors were assessed on
      an autonomically mediated response, the increase in HR induced by tail pinch, in
      rats anesthetized with urethane. Intra-MFC or AIC injections of an antagonist of
      beta-adrenoceptors reduced the magnitude of the HR response to pinch. Injections
      of an agonist of beta-adrenoceptors into these regions increased basal HR but did
      not affect the pinch response. Injections of drugs acting at alpha-adrenoceptors
      were without effect. When injected alone, drugs acting at DAergic receptors did
      not effect basal HR or the response to pinch, but intra-AIC injections of a
      combination of a D2 antagonist and an agonist of beta-adrenoceptors increased the
      magnitude of the pinch response. These results suggest that catecholamines,
      especially NA, released in the frontal cortex are important modulators of the
      basal and stress-induced output of the ANS.

PMID- 9001725
TI  - The effects of intranasal infusion of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) upon catecholamine concentrations within olfactory
      bulbs and corpus striatum of male mice.
AB  - Male C57/B1 mice received bilateral intranasal infusions of saline, MPTP or an
      intraperitoneal injection of MPTP. Infusions were performed using a peristaltic
      pump at a setting of 100 microliters/min. The MPTP, diluted in saline at
      concentrations of 2 mg/ml, was infused over 15 (0.1 mg) or 30 (0.2 mg) s, while
      the saline (control) infusions were of 30 s duration. In a separate group of
      mice, MPTP was injected via the intraperitoneal route at a dose equivalent to
      that of the 30-s intranasal concentration (0.2 mg). At 7 days post-treatment,
      catecholamine concentrations were determined from the olfactory bulbs and corpus
      striatum. Concentrations of norepinephrine within both the olfactory bulbs and
      corpus striatum of mice receiving the intranasal infusion of MPTP were
      significantly lower than those of the intranasal saline and intraperitoneal MPTP
      treated mice. No significant differences in olfactory bulb or corpus striatal
      dopamine concentrations were obtained as a function of these treatments. These
      results demonstrate that intranasal infusion of MPTP at low concentrations
      (approximately 7.0 mg/kg) can significantly reduce noradrenergic, but not
      dopaminergic, concentrations within the olfactory bulbs and corpus striatum. By
      contrast, equivalent concentrations of MPTP administered through intraperitoneal
      injection were without effect. It appears that the olfactory system may represent
      a particularly sensitive route for the receipt and transport of the neurotoxin
      MPTP into the brain.

PMID- 9001727
TI  - Identification of a saturable uptake system for deoxyribonucleosides at the blood
      brain and blood-cerebrospinal fluid barriers.
AB  - Substances can enter the brain either directly across the blood-brain barrier or
      indirectly across the choroid plexuses and arachnoid membrane (blood-CSF barrier)
      into the CSF and then by diffusion into the brain. Earlier studies have
      demonstrated a saturable thymidine uptake across the blood-CSF barrier, but not
      across the blood-brain barrier. In this study transport of [3H]thymidine across
      both barriers was measured in vivo by means of a bilateral vascular brain
      perfusion technique in the anaesthetised guinea-pig. This method allows
      simultaneous and quantitative measurement of slowly penetrating solutes into both
      brain and CSF, under controlled conditions of arterial inflow. The results of the
      present study carried out over perfusion periods of up to 30 min indicated a
      progressive uptake of [3H]thymidine into brain and CSF, which was found to be
      significantly greater than the transport of D-[14C]mannitol (a plasma space
      marker). Furthermore, the addition of 1 mM unlabelled thymidine in the perfusate
      caused saturation of [3H]thymidine uptake into both brain and CSF. In conclusion,
      these findings suggest that thymidine can cross both the blood-brain and blood
      CSF barriers in the guinea-pig by carrier-mediated transport systems.

PMID- 9001728
TI  - Involvement of GABAB receptor systems in experimental depression: baclofen but
      not bicuculline exacerbates helplessness in rats.
AB  - There are two gamma-aminobutyric acid (GABA) hypotheses of the antidepressants
      action: an increase in GABAA neurotransmission or a decrease in GABAB
      neurotransmission may contribute to action of antidepressants. In this study,
      involvement of GABAA and GABAB receptor systems was examined in the learned
      helplessness paradigm in rats. Rats were injected with bicuculline or baclofen
      for 14 days. On day 14, the rats were subjected to 15 inescapable shocks. On day
      15, they underwent the 40-trial escape test. Baclofen exacerbated the escape
      failures in the rats subjected to the inescapable shocks, although baclofen had
      no effects in the animals without shock pre-treatment. Bicuculline failed to
      influence the escape failures in the rats with the 15-shock pre-treatment. These
      results suggest that the long-term increase in GABAB neurotransmission but not
      the long-term attenuation of GABAA neurotransmission may be related to
      helplessness in rats.

PMID- 9001729
TI  - Chronic, post-injury administration of D-cycloserine, an NMDA partial agonist,
      enhances cognitive performance following experimental brain injury.
AB  - The purpose of this study was to determine the effect of augmenting NMDA receptor
      activation on cognitive deficits produced by traumatic brain injury (TBI).
      Specifically, D-cycloserine (DCS), a partial agonist of the NMDA-associated
      glycine site, was tested as a potential cognitive enhancer. Rats were injured
      using lateral fluid percussion TBI (2.8 +/- .10 atm). On days 1-15 post-injury,
      animals were injected (i.p.) with vehicle (n = 8), 10 mg/kg (n = 9), or 30 mg/kg
      (n = 8) of DCS. Sham-injured animals treated with either vehicle (n = 8) or 30
      mg/kg of DCS (n = 8) were used for comparison. On days 11-15 post-injury,
      cognitive function was assessed using the Morris water maze (MWM). Results
      indicate that the 30 mg/kg dose of DCS significantly attenuated memory deficits
      as compared to injured vehicle-treated animals (P < 0.01). Analysis also revealed
      that performance of the injured-DCS (30 mg/kg) group was not significantly
      different from sham-injured animals treated with vehicle (P > 0.10). In contrast,
      the 10 mg/kg dose of DCS was ineffective in reducing injury-induced memory
      deficits. DCS (30 mg/kg) also significantly improved the spatial memory of sham
      injured animals when compared with sham-injured animals treated with vehicle (P <
      0.05). In conclusion, chronic, post-injury enhancement of the NMDA receptor is an
      effective strategy for ameliorating TBI-associated cognitive deficits.

PMID- 9001730
TI  - Preconditioning of primary rat neuronal cultures against ischemic injury:
      characterization of the "time window of protection'.
AB  - Primary rat neuronal cultures can be preconditioned against ischemic damage by
      several mechanisms. In the present study we established a new model system in
      order to characterize the "time window of protection' obtained by preconditioning
      of neurons with adenosine. Ischemia was simulated by exposure of the cultures to
      iodoacetate (100 microM) for 150 min, with a post-ischemic reperfusion period of
      60 min. Ischemic injury was assessed by the release of lactic dehydrogenase (LDH)
      to the medium during the ischemic period and ischemia-reperfusion damage by the
      Trypan blue exclusion test. Exposure of the neuronal cultures to the ischemic or
      ischemia-reperfusion insult resulted in severe damage to the neurons, manifested
      for the former insult in a 5.4-fold increase in the release of LDH and for the
      latter insult in an 8.5-fold increase in the proportion of stained cells by the
      Trypan blue exclusion test. Preconditioning by short exposure (5 min) of the
      cultures to iodoacetic acid (simulating sublethal ischemia), or to adenosine (1
      mM) and the A1 adenosine receptor agonist N6-(R)-phenylisopropyladenosine (R-PIA;
      1 and 100 microM), prior to the insult, partially protected the neurons against
      the damage. The time-course of the development and waning of the resistance
      against the two insults following preconditioning exhibited different patterns.
      The resistance obtained against the ischemic insult developed rapidly, being
      maximal for all substances at 10 min (the shortest time window studied), and
      lasted up to 1 h for iodoacetate, 3 h for R-PIA and 24 h for adenosine. In
      contrast, the protection induced by adenosine and R-PIA against ischemia
      reperfusion injury developed relatively slowly, being maximal at 3 h, but lasted
      longer, up to 48 h. At this time the time-response curve exhibited a second peak
      of protection. The waning of protection against the two insults was found to
      continue into a period of increased sensitivity to the insults. This phenomenon
      was more intense for preconditioning with iodoacetate, and especially against the
      ischemic injury. The results suggest that in the neurons, different mechanisms
      may mediate the adenosine-induced preconditioning against the ischemic or
      ischemia-reperfusion injury. In addition, the results support the possibility
      that the relatively long "time window of protection', induced by adenosine and R
      PIA against ischemia-reperfusion insult, reflects a combination of two different
      preconditioning mechanisms.

PMID- 9001731
TI  - Modulation of morphine-induced antinociception by ibogaine and noribogaine.
AB  - The potential modulation of morphine antinociception by the putative anti
      addictive agent ibogaine and its active metabolite (noribogaine) was investigated
      in rats with the radiant heat tail-flick test. Ibogaine pretreatment (40 mg/kg,
      i.p., 19 h) significantly decreased morphine (4 mg/kg, s.c.) antinociception,
      with no effects in the absence of morphine. However, co-administration of
      ibogaine (1-40 mg/kg, i.p.) and morphine (4 mg/kg, s.c.) exhibited a dose
      dependent enhancement of morphine antinociception. Co-administration of
      noribogaine (40 mg/kg, i.p.) and morphine also resulted in an increase in
      morphine antinociception, while noribogaine pretreatment (19 h) had no effect on
      morphine antinociception. The results show that ibogaine acutely potentiates
      morphine antinociception and that noribogaine could be the active metabolite
      responsible for this effect. However, the inhibitory effects of a 19 h ibogaine
      pretreatment, which resemble ibogaine-induced inhibition of morphine's stimulant
      properties, cannot be accounted for by noribogaine.

PMID- 9001732
TI  - Distribution of alpha 2-adrenoceptors in the human locus coeruleus.
AB  - Recent reports of specific topographic patterns of cell loss in the locus
      coeruleus (LC) in psychiatric and neurologic disorders underscores the need for
      detailed neurochemical analyses of this cell group. In this study, the anatomical
      distribution of alpha 2-adrenoceptors and its relationship to the distribution of
      noradrenergic neurons in the human LC was studied. Quantitative autoradiography
      was used to assess the binding of [125I]p-iodoclonidine ([125I]PIC) to alpha 2
      adrenoceptors coordinately with counts of neuromelanin-containing cells in tissue
      sections cryocut at 10-13 levels along the rostrocaudal axis of the LC. Pontine
      brain tissue was obtained postmortem from 7 subjects dying of natural or
      accidental causes, ranging in age from 26 to 78 years. Both the binding of
      [125I]PIC and number of neuromelanin-containing cells were differentially
      distributed along the LC axis (P < 0.01) with almost identical topographical
      patterns. The highest concentration of binding and the greatest number of
      neuromelanin-containing cells per section occurred near the middle portion of the
      nucleus. There was a significant correlation between the number of neuromelanin
      containing cells per section and the specific binding of [125I]PIC at any
      particular level of the LC (r2 = 0.56; P < 0.0001). The highest and lowest
      amounts of [125I]PIC binding in the LC were observed in the youngest and oldest
      subjects, respectively, and this trend was parallelled by a significant negative
      correlation between the number of neuromelanin-containing cells at a given level
      and age (r2 = 0.85; P < 0.003). The uneven distribution of alpha 2-adrenoceptors
      in the LC demonstrates the importance of anatomical specificity when performing
      quantitative studies of LC protein chemistry in psychiatric and neurologic
      disorders.

PMID- 9001733
TI  - Etorphine elicits anomalous excitatory opioid effects on sensory neurons treated
      with GM1 ganglioside or pertussis toxin in contrast to its potent inhibitory
      effects on naive or chronic morphine-treated cells.
AB  - The ultra-potent opioid analgesic, etorphine, elicits naloxone-reversible, dose
      dependent inhibitory effects, i.e., shortening of the action potential duration
      (APD) of naive and chronic morphine-treated sensory dorsal root ganglion (DRG)
      neurons, even at low (pM-nM) concentrations. In contrast, morphine and most other
      opioid agonists elicit excitatory effects, i.e., APD prolongation, at these low
      opioid concentrations, require much higher (ca. 0.1-1 microM) concentrations to
      shorten the APD of naive neurons, and evoke only excitatory effects on chronic
      morphine-treated cells even at high > 1-10 microM concentrations. In addition to
      the potent agonist action of etorphine at mu-, delta- and kappa-inhibitory opioid
      receptors in vivo and on DRG neurons in culture, this opioid has also been shown
      to be a potent antagonist of excitatory mu-, delta- and kappa-receptor functions
      in naive and chronic morphine-treated DRG neurons. The present study demonstrates
      that the potent inhibitory APD-shortening effects of etorphine still occur in DRG
      neurons tested in the presence of a mixture of selective antagonists that blocks
      all mu-, delta- and kappa-opioid receptor-mediated functions, whereas addition of
      the epsilon (epsilon)-opioid-receptor antagonist, beta-endorphin(1-27) prevents
      these effects of etorphine. Furthermore, after markedly enhancing excitatory
      opioid receptor functions in DRG neurons by treatment with GM1 ganglioside or
      pertussis toxin, etorphine shows excitatory agonist action on non-mu-/delta
      /kappa-opioid receptor functions in these sensory neurons, in contrast to its
      usual potent antagonist action on mu-, delta- and kappa-excitatory receptor
      functions in naive and even in chronic morphine-treated cells which become
      supersensitive to the excitatory effects of mu-, delta- and kappa-opioid
      agonists. This weak excitatory agonist action of etorphine on non-mu-/delta
      /kappa-opioid receptor functions may account for the tolerance and dependence
      observed after chronic treatment with extremely high doses of etorphine in vivo.

PMID- 9001734
TI  - Constructional apraxia in Alzheimer's disease correlates with neuritic
      neuropathology in occipital cortex.
AB  - A variety of measures of neuropathology in Alzheimer's disease (AD) correlate
      with dementia severity. However, the role of beta-amyloid protein and abnormally
      phosphorylated tau protein in the decline of specific cognitive abilities is
      unknown. "Constructional praxis' (e.g., copying, constructing) is believed to
      require integrity of the parietal-occipital lobes. Unlike most other cognitive
      tasks, some AD patients are able to perform some constructional tasks even late
      in the disease course. Thus, it may be an ideal task to evaluate the relationship
      between various measures of AD neuropathology and cognitive performance. Fixed
      brain tissue was obtained from 16 AD patients who were cognitively assessed
      shortly before death. Parietal, frontal, entorhinal, and occipital cortices were
      examined by immunocytochemistry for beta-amyloid protein and abnormally
      phosphorylated tau protein at both early and later stages of neuropil thread and
      tangle formation. Constructional praxis in AD was strongly related to early-stage
      tau hyperphosphorylation in occipital cortex. Praxis ability was specific in that
      it was not significantly related to pathology in other areas and non-constructive
      tasks were not associated with occipital cortex pathology. In contrast, global
      dementia severity was related to beta-amyloid deposition in entorhinal, parietal,
      and frontal regions. These findings suggest that occipital cortex is critical for
      some constructional praxis tasks and that some regionally localizable tasks may
      be good indices of underlying pathology in corresponding brain regions.

PMID- 9001735
TI  - Fructose-1,6-bisphosphate after hypoxic ischemic injury is protective to the
      neonatal rat brain.
AB  - Fructose-1,6-bisphosphate (FBP) has been shown to attenuate central nervous
      system injury in adult animals. We evaluated whether FBP given after an ischemic
      hypoxic insult is protective to the developing brain in a neonatal rat model of
      hypoxia-ischemia. Postnatal day 7 rat pups were subjected to focal ischemia
      followed by global hypoxia and then administered either FBP or saline
      intraperitoneally. A dose of 500 mg/kg or greater of FBP significantly reduced
      the amount of injury such that 55% of FBP- vs. 17% of saline-treated rats had no
      injury; 6% of FBP- and 47% of saline-treated rats had severe damage (P = 0.004).
      There was less infarcted brain in FBP-treated rats (12 +/- 11% vs. 37 +/- 32%; P
      = 0.005); and fewer FBP-treated rats had > 30% ipsilateral cortical injury (12%
      of FBP- vs. 50% of saline-treated rats; P = 0.002). FBP lowered serum calcium
      levels during the first 24 h after the insult without significant changes in
      ionized calcium or osmolarity. These results indicate that FBP treatment
      administered systemically after hypoxia-ischemia reduces CNS injury in neonatal
      rats.

PMID- 9001736
TI  - Different central opioid receptor subtype antagonists modify maltose dextrin and
      deprivation-induced water intake in sham feeding and sham drinking rats.
AB  - Different central opioid receptor subtypes participate in the mediation of
      intakes of simple (sucrose: mu, kappa 1) and complex (maltose dextrin: mu)
      carbohydrates as well as deprivation-induced water intake (mu) under real-feeding
      and real-drinking conditions. An identical pattern of mu and kappa 1 mediation of
      sucrose intake was observed in sham-feeding rats as well, suggesting their
      actions on orosensory mechanisms supporting sucose intake. The present study
      examined whether centrally administered general (naltrexone: 1-50 micrograms), mu
      (beta-funaltrexamine: 1-20 micrograms), mu 1 (naloxonazine: 50 micrograms), kappa
      1 (nor-binaltorphamine: 1-20 micrograms), delta 1 ([D-Ala2, Leu5, Cys6]
      enkephalin: 10-40 micrograms) or delta 2 (naltrindole isothiocyanate: 20
      micrograms) opioid subtype antagonists altered either maltose dextrin (10%)
      intake during sham feeding or deprivation (24 h)-induced water intake during sham
      drinking in rats with gastric fistulas. Sham feeding significantly increased
      maltose dextrin intake (180%) and sham drinking significantly increased
      deprivation-induced water intake (256%) over a 60 min time course. Naltrexone
      significantly and dose-dependently reduced maltose dextrin intake (78%) in sham
      feeding rats, and deprivation-induced water intake (51%) in sham drinking rats.
      Maltose dextrin intake in sham feeding rats was significantly reduced by either
      kappa 1 (69%) or delta 1 (59%) opioid antagonism, was significantly increased by
      mu 1 antagonism (43%), and was not significantly affected by either mu or delta 2
      opioid antagonism. Deprivation-induced water intake in sham drinking rats was
      significantly reduced by either mu (41%), mu 1 (28%), delta 1 (48%) or delta 2
      (28%) opioid antagonism, but was not significantly affected by kappa 1 opioid
      antagonism. The difference in opioid receptor subtype mediation of maltose
      dextrin intake in real feeding and sham feeding conditions suggest that kappa 1
      and delta 1 receptors are involved in the orosensory mechanisms supporting
      maltose dextrin intake, while mu receptors are involved in the ingestive and post
      ingestive mechanisms supporting maltose dextrin intake. The different patterns of
      opioid involvement in sucrose and maltose dextrin intake in sham feeding and real
      feeding conditions provide further support for the hypothesis that at least two
      different carbohydrate taste systems exist. The difference in opioid receptor
      subtype mediation of deprivation-induced water intake in real drinking and sham
      drinking conditions may reflect the removal in the sham drinking condition of a
      mu-mediated prerestorative satiety mechanism, and the unmasking of other opioid
      mediated signalling mechanisms.

PMID- 9001737
TI  - Neuronal expression of Fos-like protein along the afferent pathway of the milk
      ejection reflex in the sheep.
AB  - This study was designed to reveal the relay stations of the afferent branch of
      the milk-ejection reflex in the sheep, by examining the effect of nipple
      stimulation on the expression of Fos protein along the spino-hypothalamic axis.
      Immunocytochemical detection of Fos protein after manual nipple stimulation in
      nonlactating ewes revealed immunolabeled neurons located exclusively
      ipsilaterally in the 3rd and 4th lumbar spinal ganglia, the medial part of
      laminae I-III of the 3rd and 4th lumbar spinal segments, the lateral cervical
      nucleus, the dorsal column nuclei, and bilaterally in the hypothalamic
      paraventricular nucleus. These findings selectively demonstrate for the first
      time those cell groups mediating the neuroendocrine effects of nipple
      stimulation.

PMID- 9001738
TI  - Differential induction of Fos in the female rat brain following different amounts
      of vaginocervical stimulation: modulation by steroid hormones.
AB  - Vaginocervical stimulation (VCS), produced either by copulation with intromission
      or by manual stimulation of vagina and cervix with a glass rod, induces
      neuroendocrine and behavioral responses that are critical for female reproduction
      in many species. We and others have shown that Fos mRNA and protein are induced
      within different estrogen-concentrating and -non-concentrating regions of the
      female rat brain following copulation with intromission and manual VCS. In the
      present study, we investigated the amount of distributed VCS required to induce
      Fos immunoreactivity within estrogen-concentrating regions of the medial preoptic
      area, lateral septum, bed nucleus of the stria terminalis, ventromedial
      hypothalamus, medial amygdala, and mesencephalic central gray, and whether
      estrogen and progesterone could alter the threshold or pattern of induction.
      Ovariectomized rats were administered estradiol benzoate (10 micrograms) 48 h and
      progesterone (500 micrograms) 4 h before receiving either 0, 1, 5, 10, 20, 30,
      40, or 50 manual VCSs with a lubricated glass rod. Ovariectomized hormone control
      rats received injections of the sesame oil vehicle 48 and 4 h before VCS. All
      rats were sacrificed 75 min after the first VCS. Fos immunoreactivity was induced
      differentially by VCS within the different regions, and the hormones either
      augmented, inhibited, or had no effect on the induction. These data demonstrate
      that cells within different estrogen-concentrating regions of the female rat
      brain are differentially sensitive to VCS, and that steroid hormones can either
      increase or decrease the amount of Fos induced by different amounts of VCS.
      Different brain regions may participate in gating the sensory information of VCS
      into different behavioral and neuroendocrine events.

PMID- 9001739
TI  - Localization of nitric oxide synthase in the brain of the frog, Xenopus laevis.
AB  - Nitric oxide synthase was localized in the brain of the South african clawed frog
      by NADPH diaphorase histochemistry and immunohistochemistry. All structures
      stained by the antiserum also displayed NADPH diaphorase activity. The fiber
      bundles of the terminal nerve, however, were positive for NADPH diaphorase but
      were not immunoreactive. In the forebrain, neurons expressing nitric oxide
      synthase were concentrated to the pallium, striatum, nucleus accumbens and
      anterior entopeduncular nucleus. Strongly stained neurons in the diencephalon
      were detected in the lateral thalamus, the tuberculum posterior and in the
      ventral hypothalamus. In the mesencephalon, the tectum and the magnocellular
      nucleus of the torus semicircularis contained many positive cells. Farther
      caudally, intensely stained neurons were abundant in an area corresponding to the
      anuran locus coeruleus, in the descending nucleus of the trigeminus and the
      inferior reticular nucleus. In the cerebellum, Purkinje cells were weakly
      stained. In summary, the expression pattern of nitric oxide synthase in the
      anuran brain reveals similarities to that of other vertebrates. The strongly
      positive cell group in the locus coeruleus may correspond to cholinergic cell
      groups in the mesopontine area in mammals.

PMID- 9001740
TI  - Sociosexual stimuli affect ER- and PR-mRNA abundance in the hypothalamus of all
      female whiptail lizards.
AB  - Hormone-dependent sociosexual behaviors of the displaying individual regulate the
      abundance of estrogen receptor- and progesterone receptor-mRNA in sex steroid
      hormone-concentrating brain areas of the partner. This effect of behavior on gene
      expression in the brain is independent of the gonads.

PMID- 9001741
TI  - Analysis of the retinohypothalamic tract in congenic albino and pigmented rats.
AB  - To determine whether differences in the retinohypothalamic tract (RHT) were
      related specifically to albinism, we analyzed the distribution and trajectory of
      this pathway in congenic F344-c/+ albino and pigmented rats using the inactive
      subunit of cholera toxin conjugated to horseradish peroxidase as an anterograde
      tracer. We found that the overall volume of the tract in the albino rats was
      greater than in the pigmented rats (P < 0.05). We also noted shape differences.

PMID- 9001742
TI  - Circadian rhythm in light response in suprachiasmatic nucleus neurons of freely
      moving rats.
AB  - Long-term recordings of single SCN units were performed in freely moving rats
      simultaneously with multiunit recordings and evidence is presented for a daily
      change in light-responsiveness. SCN light response is high during the night and
      low during the day. We conclude that this difference is caused by a change in
      sensitivity, with higher sensitivities at night. Moreover, we demonstrate that
      the circadian rhythm in SCN light response is the result of the integrated
      behaviour of similarly behaving single SCN units.

PMID- 9001743
TI  - Prearraignment forensic evaluations: toward a new policy.
AB  - Prearraignment forensic evaluations are forensic psychiatric evaluations
      performed on a suspect soon after his or her arrest. In the guise of ethics, the
      committee members who originated this code have imposed apparently personal and
      political views on all members of respective professional organizations in order
      to circumvent rulings of the judiciary, including the U.S. Supreme Court. The
      prohibition against prearraignment evaluations represents a misapplication of
      physician-as-healer-based medical ethics--in which the core principle is the
      physician's beneficence to the patient--to the forensic arena, where no physician
      patient relationship exists and healing is not the purpose. The ethical code
      prohibiting prearraignment evaluations reflects misguided paternalism and
      political bias, as well as being in direct conflict with current law. Whether or
      not prearraignment evaluations should be permitted is primarily a Fifth and Sixth
      Constitutional Amendment issue more than a traditional medical-ethical one.
      Ethics and the law, when both are examined carefully, suggest prearraignment
      evaluations are proper when performed responsibly.

PMID- 9001745
TI  - When Munchausen becomes malingering: factitious disorders that penetrate the
      legal system.
AB  - Psychiatrists and other physicians are usually familiar with factitious
      disorders, but attorneys and judges usually are not. Cases involving factitious
      disorders may enter the civil legal system in a number of ways and cause
      incorrect judgements, financial costs, and inappropriate medical care if these
      disorders are not identified. Psychiatric consultants may play a key role in
      identifying these cases and educating legal personnel about factitious disorders.
      This article describes three cases in which persons with factitious disorders
      entered the civil litigation system. The role of the psychiatrist in these cases
      is discussed. Clues to the identification of factitious disorders are described.
      The article also discusses the differentiation of factitious disorders from
      malingering and other forms of abnormal illness behavior, such as conversion,
      hypochondriasis, and somatization disorders. The concepts of primary and
      secondary gain in relationship to illness behaviors are elaborated.

PMID- 9001744
TI  - Capacity to consent to voluntary hospitalization: searching for a satisfactory
      Zinermon screen.
AB  - Half a decade ago, the Zinermon court announced the need for clinicians to
      evaluate the competence of people with mental illness to consent to voluntary
      hospital admission, but the court did not specify the test of capacity that
      mental health professionals should use. As has occurred in other areas dealing
      with legal competence, there is a need for the field to develop standardized
      assessment procedures for evaluating capacity to consent to voluntary
      hospitalization. Both theoretical and practical considerations suggest that these
      procedures should be modeled after what S. K. Hoge has termed a "weak" model of
      consent. This and other studies of the ability of mentally ill persons to
      understand disclosed information suggest that their level of understanding may be
      assessed optimally with measures that utilize recognition rather than recall
      response elicitation formats.

PMID- 9001746
TI  - Tales of the crypt for psychiatrists: mourning, melancholia, and mortuary
      malpractice.
AB  - Death awaits all, leaving in its wake relatives and friends affected by the loss
      of a loved one. Immediately following death, the funeral process begins,
      resulting in permanent burial in a cemetery. This report investigates the
      dysfunctional interactions between grief-stricken relatives and mortuaries that
      are associated with civil litigation for negligence. Psychiatric evaluations of
      25 bereaved plaintiffs from nine separate lawsuits were performed. In addition,
      medical records and legal pleadings were reviewed as sources of additional
      information. General themes from the clinical material are identified and
      illustrated by two cases. Surviving relatives are in an acute state of emotional
      turmoil, rendering them exquisitely sensitive to lapses in expected routine and
      perceived disrespect toward the decreased. These issues are intensified when the
      circumstances of the death were traumatic, when the relationship with the
      deceased was ambivalent, when specific cultural and religious factors are
      present, and when the influence of litigation is felt. If the burial process is
      disrupted, civil suits for negligence may be filed that exacerbate grief and
      challenge the psychiatrist's efforts to resolve diagnostic ambiguity in the face
      of emotionally charged cultural and religious practices.

PMID- 9001747
TI  - Postconcussional disorder and loss of consciousness.
AB  - Postconcussional disorder (PCD) has been described in the psychiatric,
      neurological, neuropsychological, and rehabilitation medicine literature for many
      years. PCD has recently been introduced into DSM-IV, appearing in an appendix
      that contains a number of proposals for new categories and axes that were
      suggested for possible inclusion in DSM-IV. There are some major difficulties
      with the proposed criteria for PCD. This article explores some of these
      difficulties, particularly focusing on the criteria of loss of consciousness
      (LOC). A review of the literature demonstrates that LOC is not necessary for PCD
      to occur. The major difficulty with the DSM-IV criteria is the definition of
      concussion. The article suggests that, instead, the criteria for mild traumatic
      brain injury, as defined by the American Congress of Rehabilitation Medicine, may
      be more appropriate.

PMID- 9001748
TI  - A clinical study of competency in psychiatric inpatients.
AB  - A 15-item questionnaire used to evaluate competency to consent to psychiatric
      hospitalization was validated using a blind forensic psychiatric interview. The
      statistical correlation was excellent with p < .001. The questionnaire also
      correlated highly with the Mini-Mental State exam (p < .05), the Brief
      Psychiatric Rating Scale (p < .05), and the Weschler Adult Intelligence Scale
      Revised vocabulary subtest (p < .01). This questionnaire may be a useful
      instrument for preliminary screening of psychiatric patients for competency to
      consent to hospitalization and general psychiatric treatment.

PMID- 9001749
TI  - Patients' attitudes toward having been forcibly medicated.
AB  - Forced antipsychotic medication procedures are generally perceived to be
      clinically necessary options, albelt violations of individuals' bodies and
      autonomy. Previous studies have explored forcibly medicated patients' attitudes
      concerning these procedures, but as patients were interviewed while still in the
      hospital, this may have affected their responses. We interviewed consecutively
      forcibly medicated English-speaking acute-care inpatients after their discharge
      to the community. The interviews were conducted by telephone by a clinician not
      involved with their treatment. Of 65 such patients, 7 had already been
      rehospitalized, 3 could not recall the procedure, and 25 others refused the
      interview or were not locatable. Of the 30 who were successfully interviewed,
      only 47 percent had received any forced injections; the remainder had accepted
      oral medication under duress. Recollecting their experiences, 57 percent
      professed fear of side effects, 17 percent feared "addiction," and 17 percent
      objected to others' controlling them. Forty percent recalled feeling angry, 33
      percent helpless, 23 percent fearful, 13 percent embarrassed, but 23 percent were
      relieved. Surprisingly, 60 percent retrospectively agreed with having been
      coerced, 53 percent stating they were more likely to take medication voluntarily
      in the future. Other forcibly medicated patients had poorer outcomes, such as
      rapid readmission or discharge to a state hospital: those patients may have
      harbored more negative feelings. However, a substantial fraction of the patients
      who were reached in the community appeared to support having received medication
      forcibly as inpatients.

PMID- 9001751
TI  - Trading forensic and family commitments.
AB  - This pilot study explores the balancing of conflicting family and forensic
      commitments among forensic experts. Drawing upon consumer preference theory and
      behavioral economics, the authors devised an instrument to elicit choices between
      upholding family commitments and professional commitments. The instrument was
      administered to 15 forensic experts, and the data were used to construct trading
      functions for each individual. These functions were examined to reveal the
      decision-making process behind balancing conflicting sets of commitments. The
      study also examined the relationship between the trading functions and each
      participant's attitude toward the role of the expert witness, as well as some
      personal characteristics.

PMID- 9001750
TI  - A comparison of treatment of paraphilias with three serotonin reuptake
      inhibitors: a retrospective study.
AB  - Treatment of the paraphilic disorders using behavioral, cognitive,
      pharmacological, and social interventions has been shown to have limited success
      with poorly motivated or noncompliant patients. Researchers have speculated on
      the role of the serotonergic system in the paraphilic disorders. Recent anecdotal
      studies have reported successful results with the selective serotonin reuptake
      inhibitors (SSRIs) in the treatment of the paraphilic disorders. This
      retrospective study evaluates and compares the effectiveness of three SSRIs in a
      group of paraphilics (N = 58). The individual effectiveness of fluvoxamine,
      fluoxetine, and sertraline were examined and compared. Results found that the
      severity of fantasies decreased and that there were no significant differences in
      the reported efficacy between fluvoxamine, fluoxetine, and sertraline. Although
      double blind placebo crossover studies are still needed to assess the efficacy of
      these agents, this study further supports the growing body of literature on the
      potential use of these drugs in the treatment of the paraphilias.

PMID- 9001752
TI  - Posttraumatic stress disorder, pulp fiction, and the press.

PMID- 9001753
TI  - Basic science of small cell lung cancer.
AB  - The unique phenotype expressed by small cell lung cancer (SCLC) cells is
      responsible for the distinct clinical behavior of SCLC. Basic research of SCLC is
      aimed at identifying and characterizing the unique attributes of SCLC cells that
      distinguish SCLC from other forms of lung cancer and contribute to the malignant
      behavior of SCLC. This article summarizes recent scientific advances in this
      area. Specific issues which are addressed include our current understanding of
      how SCLC arises, the origin and consequences of the neuroendocrine phenotype
      expressed by SCLC cells, and the role of SCLC adhesion molecules in SCLC
      metastasis.

PMID- 9001754
TI  - Neuroendocrine tumors of the lung. Pathology and molecular biology.
AB  - Our understanding of the molecular genetic changes in lung cancer pathogenesis is
      advancing rapidly with several specific genes and chromosomal regions having been
      identified. As the biochemical functions of the proteins encoded by these genes
      are discovered, they appear to fall into several growth regulatory pathways. The
      large number of genetic lesions in clinically evident lung cancer has prompted
      searching for mutations in preneoplastic lung tissue before the pathologic
      evidence of cancer as a tool for early molecular diagnosis. In addition, these
      markers need to be rigorously assessed for their prognostic importance. Finally,
      understanding the molecular basis of lung cancer should allow "translation" of
      these findings from the bench to the bedside. These include very early molecular
      diagnosis, identification of persons at highest risk of developing lung cancer to
      allow for more effective smoking cessation strategies, chemoprevention, and very
      early treatment studies (clinical studies beginning); rational development of
      novel therapies such as immunization against tumor-specific mutant peptides
      (clinical studies ongoing); blocking the expression of activated oncogenes (such
      as with antisense or triple helix agents); and replacing defective tumor
      suppressor genes (clinical studies ongoing).

PMID- 9001755
TI  - Differential diagnosis of small cell neuroendocrine carcinoma of the lung.
AB  - The clinical significance of a tumor classification rests in its usefulness to
      predict the natural history and response to therapeutic intervention of given
      tumor types. In this context, the importance of distinguishing between SCNC and
      neoplasms with which it has been confused is evident. In 1990, we re-evaluated a
      series of 50 patients who underwent a complete resection for tumors in which the
      diagnosis of small cell carcinoma was thought to have been established. Adjuvant
      therapy was given to nearly all patients, either pre- or postoperatively. We re
      evaluated the histology of these tumors in light of the differential diagnosis
      described previously and correlated the diagnosis with the survival curves. We
      found that WDNC of any subtype has a much better prognosis than SCNC. Even
      locally advanced WDNC has a better prognosis than stage I completely resected
      SCNC (Fig. 9). Others have reported similar observations based on their own
      retrospective studies. Preliminary observations on completely resected chest wall
      PNETs suggest that these tumors also have a more favorable prognosis than SCNC.
      Given the difficulty in distinguishing SCNC from other tumors described
      previously, and the fact that most SCNC are treated without resection, the
      clinician should be familiar with certain features that are unusual for SCNC,
      and, therefore, suggest reconsideration of the diagnosis. In our patient
      population, SCNC is rarely seen in a lifetime nonsmoker and is distinctly unusual
      in an ex-smoker of 15 years of longer. T with chest wall invasion is a very
      unusual clinical stage for true SCNC. Small cell neuroendocrine carcinoma can
      invade the chest wall, but this is almost always in the presence of extensive
      mediastinal or distant metastases. Clinicians should also be wary of accepting
      the diagnosis of SCNC when serial radiographs suggest that the lesion is not
      growing or growing very slowly. Untreated SCNC usually demonstrates some growth
      over a 3-month period of observation. Finally, SCNC tends to be a chemosensitive
      neoplasm, at least initially. The occasional tumors that do not respond tend to
      enlarge and disseminate rapidly. If a tumor neither decreases nor increases in
      diameter over a 3-month period of presumably appropriate chemo- or radiotherapy,
      the diagnosis of SCNC should be questioned. Over the last 15 years, several
      reports have suggested a role for resection in the management of SCNC, especially
      for tumors diagnosed at an early stage. Other reports may have unwittingly
      exaggerated the long-term survival of SCNC treated by currently available chemo-
      and radiotherapy protocols. A careful re-evaluation of the diagnostic material in
      such cases may lead to more consistent results and the development of more
      rational therapeutic protocols.

PMID- 9001756
TI  - Paraneoplastic syndromes associated with small cell lung cancer.
AB  - The term paraneoplastic syndrome refers to the ability of some tumors to produce
      signs and symptoms at a distance from the site of the primary tumor or its
      metastases. Paraneoplastic syndromes may develop before the diagnosis of
      carcinoma is made. Paraneoplastic syndromes associated with small cell lung
      cancer (SCLC) include endocrinologic abnormalities secondary to peptide hormone
      production, and neurologic sequelae due to autoantibody production. This article
      reviews the common paraneoplastic syndromes that may occur in patients with SCLC.

PMID- 9001757
TI  - Staging of the patient with small cell lung cancer.
AB  - Patients with SCLC should have a complete history and physical examination with
      particular attention paid to symptoms and signs of extensive disease and
      paraneoplastic syndromes. Hematology and biochemistry should be obtained at the
      initial assessment. A chest radiograph will usually have been performed prior to
      diagnosis. Further imaging should then be done to determine if the patient has
      limited or extensive disease. In the nonprotocol setting, extensive radiologic
      investigations are not required once a site of metastatic disease has been
      identified. If symptoms or signs are present to indicate a site of extensive
      disease, then this should direct the next test. In the absence of any specific
      findings then either bone scan or abdominal imaging with either US or CT scanning
      may be done based on the roughly equal likelihood of metastatic disease in liver
      or bone. Because a bone scan is less expensive, it is often the next test
      selected. If the bone scan is negative, abdominal imaging should then be
      performed, followed by brain CT scan. If these investigations are negative, the
      next study should be a thoracic CT scan. Bone marrow examination is probably
      unnecessary in the nonprotocol setting unless serum LDH levels are elevated. In
      the setting of a clinical trial, complete staging should be done and even more
      precise staging using the TNM system should be considered based on the improved
      survival of patients with proven stage I disease. Using more precise staging will
      allow accurate comparisons of clinical trials and eliminate or minimize the
      question of patient selection. Surgical staging with mediastinoscopy may come to
      have a role in accurately determining stage I or II disease.

PMID- 9001758
TI  - Surgical treatment of peripheral small cell lung cancer.
AB  - Approximately 5% of small cell lung cancer (SCLC) patients present with an
      asymptomatic peripheral tumor (solitary pulmonary nodule) on "routine" chest
      radiography. In this setting, the diagnosis of SCLC is often made at thoracotomy.
      Complete resection, mediastinal lymph node sampling, and postoperative
      chemotherapy are indicated. If the diagnosis is made preoperatively, multiorgan
      scanning and mediastinoscopy are required prior to thoracotomy. Survival for
      pathologic stage I SCLC treated by surgery and postoperative chemotherapy is
      comparable to survival for surgically treated stage I non-SCLC.

PMID- 9001759
TI  - Is there a place for surgery in central small cell lung cancer?
AB  - Despite radiographic complete remission after standard induction therapy, 75% of
      SCLC patients will have tumor in the resected specimen. This and the high rate of
      local recurrence indicates that surgery may assume a greater role in the future
      if better control can be obtained for distant disease and local relapse thus
      becomes the mode of death.

PMID- 9001760
TI  - The role of chemotherapy in the treatment of small cell lung cancer.
AB  - Because small cell lung cancer (SCLC) is a systemic malignancy, chemotherapy is
      the mainstay treatment for patients with all stages of this tumor. Many
      chemotherapeutic agents have activity against SCLC, and when combined in three-
      or four-drug regimens, they produce a response in 75% to 90% of patients. Median
      survival times for patients with limited disease range from 14 to 16 months, and
      a small proportion may be cured. For extensive stage patients, median survival is
      usually less than 1 year; 2 year disease-free survival is uncommon. Current
      research is focusing on ways to increase the dose intensity of chemotherapy
      delivery.

PMID- 9001761
TI  - Role of radiotherapy in the treatment of small cell lung carcinoma.
AB  - Radiotherapy is an important component in the treatment of limited stage small
      cell carcinoma of the lung. It improves both local control and survival. This
      article reviews the scientific and clinical data that have led to combined
      therapy being considered the current standard for care of limited stage disease.
      Questions of radiation dose, treatment volume, fractionation, and integration
      with chemotherapy are discussed. New avenues of investigation to reduce toxicity
      and optimize treatment efficacy are also discussed.

PMID- 9001762
TI  - Prophylactic cranial irradiation for patients with small cell lung cancer. An
      enduring controversy.
AB  - Small cell lung cancer (SCLC) is a systemic disease that usually presents with
      locally bulky disease in the lung and mediastinal nodes, with either subclinical
      (limited stage) or detectable (extensive stage) extrathoracic metastases.
      Treatment with local modalities alone leads almost invariably to systemic
      relapse, and treatment with only systemic therapy usually results in recurrence
      at sites of initially demonstrated disease. Although prophylactic cranial
      radiation is far from an ideal solution to the problem of CNS metastases in
      patients with SCLC, it presently seems preferable to the alternative of
      observation and generally ineffective palliative treatment at time of relapse in
      the CNS.

PMID- 9001763
TI  - Practical issues in the management of the patient with small cell lung cancer.
AB  - Small cell lung cancer (SCLC) accounts for 20% of all lung cancers. More than two
      thirds of patients with SCLC present with clinically evident distant metastases.
      Patients with limited stage disease are treated with a combination of
      chemotherapy and chest radiation. Patients with extensive stage disease and good
      performance status are candidates for combination chemotherapy. Almost all
      patients relapse after an initial response. This article focuses on the common
      sense approach to the management of SCLC.

PMID- 9001764
TI  - Future directions in the therapy of small cell lung cancer.
AB  - Current therapy for small cell lung cancer seems to have reached a plateau. To
      rise off this plateau it will be necessary to improve local control through
      radiation therapy, and control of distant metastases with new chemotherapy
      strategies. It will also be necessary to treat pharmacologic sanctuaries, reduce
      treatment-related toxicities, and prevent second malignancies.

PMID- 9001766
TI  - Disposable contact lenses: where we have been--what we have learned.

PMID- 9001765
TI  - Corneal ulcers and contact lenses: where are we now?

PMID- 9001767
TI  - Alignment effects in videokeratography of keratoconus.
AB  - PURPOSE: To determine the effects of corneal apex decentration on
      videokeratography in subjects with keratoconus. We controlled corneal apex
      decentration by first locating the cone apex position and then shifting the
      fixation position by known amounts relative to the videokeratograph axis.
      METHODS: We evaluated the effect of keratoconus apex position on
      videokeratography by measuring 28 eyes (17 subjects) at 4 corneal positions: the
      vertex normal, apex, and 1 mm or 2 mm above the apex. RESULTS: When compared to
      the apex alignment values, the radius of 1 mm (mean difference: 0.27 mm; SD +/-
      0.20 mm) and 2 mm (mean difference: 0.82 mm; SD +/- 0.50 mm). The corneal
      toricity was greater at apex alignment than at the 1 mm (mean: -0.35 D; SD +/-
      1.76 D) and 2 mm (mean: 0.62 D; SD +/- 3.23 D) decentrations. CONCLUSIONS:
      Decentration of the corneal apex in keratoconus produces significant errors in
      videokeratography when using the standard alignment rather than alignment with
      the apex. When there is a decentered cone apex, videokeratograph power errors are
      greater with the standard (sagittal) power map than with the instantaneous
      (tangential) power map. The standard power map produces values for the apex
      position that are about 50% too high and values for the apex power that are from
      10 to 40% too low. Most cone shapes have significant toricity that is often not
      detected with standard videokeratograph alignment.

PMID- 9001768
TI  - A double-masked, placebo-controlled evaluation of the efficacy and safety of
      loteprednol etabonate in the treatment of giant papillary conjunctivitis.
AB  - PURPOSE: To evaluate the safety and effectiveness of loteprednol etabonate 0.5%
      ophthalmic suspension (LE) for reducing the ocular signs and symptoms
      accompanying contact lens associated giant papillary conjunctivitis (GPC). We
      conducted a randomized, double-masked, placebo-controlled, parallel study at 11
      U.S. academic or private practice clinics. METHODS: Two hundred and twenty adults
      with contact lens associated GPC were enrolled in this study. Patient were
      treated with either LE or the loteprednol etabonate vehicle (placebo), q.i.d. for
      6 weeks. Papillae, itching, lens intolerance, as well as other signs and symptoms
      of GPC (0 to 3 or 0 to 4 point severity scales), and intraocular pressure were
      measured. RESULTS: The proportion of patients treated with LE demonstrating an
      improvement in papillae of at least one grade (75%) was significantly greater
      than the proportion of those treated with placebo (50%, P < 0.001). A treatment
      difference favoring LE was also seen with improvement in itching (92% vs. 76%, P
      = 0.001) and lens intolerance (84% vs. 66%, P = 0.002). Three patients (all on
      LE) had an intraocular pressure (IOP) elevation of 10 mm Hg or higher from
      baseline on at least one on-treatment visit. Cessation of therapy was required in
      one of these patients. CONCLUSIONS: Both treatments were well tolerated and no
      serious, unexpected, treatment-related medical events were reported. The rapid
      therapeutic response, combined with the low incidence, late development, and
      transient nature of any IOP elevation suggests that LE may be helpful in treating
      GPC.

PMID- 9001769
TI  - The effects of disposable daily wear contact lenses on goblet cell count.
AB  - PURPOSE: The number of goblet cells on the inferior bulbar conjunctiva increases
      in response to daily wear contact lens use. We conducted a study to examine
      whether daily wear soft contact lenses worn on a 2-week disposable schedule would
      also induce the same goblet cell response. METHODS: Twenty-eight subjects who had
      never worn contact lenses were fit with 38% water polymacon lenses. The lenses
      were worn on a daily wear basis and replaced every two weeks over a 6-month
      period. Goblet cell count was determined by impression cytology of the inferior
      bulbar conjunctiva. RESULTS: No significant increase in goblet cell count was
      observed in the subjects during the 6 months period; the 3.23% baseline goblet
      cell count was never exceeded. In our previous study, after 6 months of
      conventional daily wear lens use, the goblet cell count increased from a baseline
      of 4.19% to 8.0%. CONCLUSIONS: It appears that wearing daily wear soft contact
      lenses on a disposable basis may be less irritating to the ocular surface than
      wearing soft contact lenses on a conventional daily wear basis.

PMID- 9001770
TI  - The use of disposable contact lenses as therapeutic lenses.
AB  - PURPOSE: To evaluate the efficacy of Acuvue contact lenses as a therapeutic
      contact lens in 33 patients with noninfectious corneal disorders. METHODS: We fit
      33 patients (21 female, 12 male) with Acuvue contact lenses. Patients were seen
      in follow-up at 24 hours, 4 days, 15 days, and then monthly. Contact lenses were
      replaced weekly. Ocular signs and symptoms related to lens tolerance were
      recorded at each follow-up visit. RESULTS: Twenty-six patients (79%) improved or
      remained asymptomatic. Seven patients (21%) were discontinued due to
      complications, intolerance, or poor fit. In the majority of patients (79%), the
      Acuvue lens was tolerated and was beneficial in the treatment of corneal disease.
      CONCLUSIONS: The Acuvue contact lens can be effectively utilized as a therapeutic
      contact lens.

PMID- 9001771
TI  - Clinical performance of the Optima toric contact lens versus the CSI toric
      contact lens.
AB  - PURPOSE: To compare the clinical performance of the Optima soft toric contact
      lens versus the CSI soft toric contact lens. METHODS: Twenty-one patients (five
      affected by allergies) were followed at 2-week intervals for 4 months in a
      prospective, randomized, double-masked study comparing the Optima soft toric
      contact lens to the CSI soft toric contact lens. RESULTS: The patients preference
      evaluation revealed a statistically significant preference for the CIS toric lens
      in 14 of 16 variables including overall lens preference (P = 0.0001). The two
      remaining variables, lens awareness (P = 0.07) and foreign body sensation (P =
      0.06), showed a trend toward a preference for the CSI toric lens. The less
      sensitive symptom ranking questionnaire revealed a significance for, or a trend
      toward, a significant difference in three of 10 variables, all in favor of the
      CSI toric lens. The mean degrees of axis rotation were 3.5* for the CSI lens and
      7.6* for the Optima lens (P = 0.0001). Factor analysis identified a clustering of
      variables around specific ranked factors. Factors related to 1) allergy status
      (.93); 2) visual function (.87); 3) ocular surface (.82); and 4) refractive
      characteristics (.71) were most significant in determining the overall clinical
      performance of these toric lenses. Allergic patients significantly preferred the
      CSI toric lens for 15 of 16 variables, whereas non-allergic patients preferred
      the CSI lens for seven of 16 variables. CONCLUSIONS: The patient preference,
      symptom ranking, and axis rotation analysis of this study revealed a superior
      performance by the CSI toric contact lens when compared to the Optima toric
      contact lens. Allergic patients revealed an even stronger and statistically
      significant preference for the CSI lens when compared to non-allergic patients.

PMID- 9001772
TI  - Comparative study of some physiologically important properties of six brands of
      disposable hydrogel contact lenses.
AB  - PURPOSE: This study examines the water content, refractive index, oxygen
      permeability (Dk), oxygen transmissibility (Dk/L), and lens thickness profile for
      six brands of disposable hydrogel contact lenses. METHODS: Refractive index was
      measured with a Bausch & Lomb Abbe Model 3L laboratory refractometer. Water
      content was read from the scale in the refractometer eyepiece. Oxygen
      permeability and transmissibility were measured by a Rehder polarographic unit
      using the procedure described in International Standards Organization (ISO)
      Standard 9913-1.2. Lens thickness profiles were measured on a Rehder Electronic
      Thickness Gauge equipped with a rotating ball anvil. RESULTS: Water content
      ranged from 38% to 62%. Lower water content lens materials had an oxygen
      permeability of about 7 x 10(-11) (cm2/sec)(mL O2/mL x mm Hg), whereas the
      permeability for the higher water content materials ranged from 20 x 10(-11) to
      30 x 10(-11). CONCLUSIONS: In theory, it is possible to design contact lenses of
      approximately the same transmissibility-when starting with materials of different
      permeabilities-by adjusting lens thickness. This was not the case with the six
      brands studied here. Some brands of contact lenses had significantly higher
      transmissibilities than others, but all had FDA approval. The clinical
      significance of different contact lens transmissibilities based on different
      definitions of thickness is discussed.

PMID- 9001773
TI  - Acanthamoeba keratitis: is water exposure a true risk factor?
AB  - PURPOSE: Water exposure has been commonly cited in the literature as a
      significant risk factor for the development of Acanthamoeba keratitis. The
      purpose of this study was to test the hypothesis that the incidence of tap and
      contaminated water exposure in Acanthamoeba keratitis patients is no higher than
      in the normal contact lens population. METHODS: We retrospectively reviewed all
      patients all patients diagnosed with Acanthamoeba keratitis at Massachusetts Eye
      & Ear Infirmary from 1990-1994, and compared this group to a control population
      of healthy contact lens wearers assessed by a self-report questionnaire. RESULTS:
      A history of water exposure was reported by 64% (seven patients) diagnosed with
      Acanthamoeba keratitis. In comparison, 100% of the control population of healthy
      contact lens wearers (100 patients) reported comparable water exposure, and 87%
      of controls reported multiple sources of water exposure. CONCLUSIONS: The finding
      that the incidence of water exposure is actually lower in patients with
      Acanthamoeba keratitis than in the general contact lens population suggests that
      water exposure may be less important, and other factors more important in the
      development of this disease than previously assumed.

PMID- 9001774
TI  - Loss of bactericidal activity from contact lens storage solutions.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of lens storage on
      the bactericidal activities of disinfecting solutions. METHODS: HYDROCURVEII (55%
      water content) soft contact lenses were soaked in OPTI-FREE Rinsing,
      Disinfecting, and Storage Solution (preserved with polyquaternium-1 [PQ-1]) or
      ReNu Multi-Purpose Solution (polyaminopropyl biguanide [PHMB]). After the lenses
      were removed, solutions were challenged with Pseudomonas aeruginosa and
      Staphylococcus aureus. Uptake of the antimicrobial agents by the lenses was
      evaluated by placing the lenses on plates seeded with S. aureus and observing for
      zones of growth inhibition. RESULTS: The bactericidal activity of the PHMB
      preserved solution decreased after 4 hours of storage time and showed no activity
      after storage for 3 days. Lenses soaked in the PHMB preserved solution produced
      zones of inhibition. The results suggest that the PHMB in the solution
      accumulates in the lens. This decreases the levels of preservative in the
      solution that is no longer available during lens storage. Neither decrease in
      bactericidal activity nor accumulation of the PQ-1 preservative in the lens
      occurred during storage with the PQ-1 solution. CONCLUSION: These results
      demonstrate that PQ-1 preserved solutions maintain bactericidal activity
      overnight and during prolonged storage without detectable uptake by lenses.

PMID- 9001775
TI  - Adherence of Pseudomonas aeruginosa to shed rabbit corneal epithelial cells after
      overnight wear of contact lenses.
AB  - PURPOSE: Previous studies have shown that contact lens oxygen transmissibility
      correlates with binding of Pseudomonas aeruginosa to the rabbit cornea after
      overnight lens wear. Studies of human lens wear stratified by oxygen
      transmissibility will be required to validate these animal results. In humans,
      bacterial binding to shed cells obtained through corneal irrigation cytology may
      provide an indirect measure of in vitro binding. The purpose of this study was to
      establish the relationship between binding to shed cells and to the residual
      corneal surface in an animal model of lens wear prior to initiation of human
      studies. METHODS: The test contact lenses used were: rigid lens A (Dk/L = 10 x
      10(-9) [cm/ sec][mL O2/mL mmHg]); rigid lens B (Dk/L = 97); soft lens A (Dk/L =
      9); soft lens B (Dk/L = 20); and, soft lens C (Dk/L = 39). There were six rabbits
      in each group, except for the soft lens C group, which had seven rabbits. After
      overnight lens wear, the corneal surface was irrigated with a corneal irrigation
      chamber to collect surface cells before exposure to a bacterial suspension (1 x
      10(7) CFU/mL) for 30 minutes. The number of bacteria adherent to the residual
      corneal surface was then assessed by CFU determination. Cells collected from the
      corneal surface (9 mL) were incubated with 1 mL bacterial suspension containing
      10(8) (CFU/mL) for 30 minutes. The number of bacteria adherent to shed cells was
      assessed by staining with acridine orange and direct counting by epifluorescence
      microscopy. RESULTS: The differences in the number of bacteria adhering to shed
      epithelial cells between the treated and the control eyes were 2.90 +/- 1.20 and
      0.23 +/- 0.41 for rigid lenses A and B, respectively, and 5.97 +/- 1.54, 3.67 +/-
      2.32, and 0.90 +/- 1.45 (bacterial/cell) for soft lenses A, B, and C,
      respectively. Overnight contact lens wear induced a significant increase in
      bacterial binding to shed corneal epithelial cells for rigid lens A and for soft
      lenses A and B. There were significant differences among lens groups (P =
      0.00017, ANOVA), with significant differences between rigid lenses A and B, soft
      lenses A and C, and soft lenses B and C. The binding of bacteria to shed cells
      was significantly correlated with the binding of bacteria to the residual corneal
      surface, both confirming and extending previous results (R = 0.78, P < 0.001).
      CONCLUSION: These results demonstrate a positive correlation between P.
      aeruginosa adherence to shed corneal cells and to the residual corneal surface in
      the rabbit eye following contact lens wear. In light of the results from prior
      animal studies, examination of the behavior of P. aeruginosa binding to
      exfoliated cells appears to be a promising and valid method for future assessment
      of similar lens-induced increases in bacterial binding in prospective human
      clinical studies.

PMID- 9001776
TI  - Rigid lens dynamics: lid effects.
AB  - PURPOSE: Lid architecture, lid tension, blink action, and blink rate may all
      influence rigid lens centration and stability. The aims of this study were to
      assess the nature of the relationship between lid geometry and lens position and
      to examine the influence of lens-lid interactions on the association between lens
      position and lens center of gravity and mass. METHODS: Eight subjects (four with
      high riding lenses and four with low riding lenses) participated in the study.
      Each subject was fit with 12 lenses-six designs in each of two materials. Lens
      center of gravity was calculated and lens mass was measured in every case. For
      each lens, the following four lens dynamics variables were assessed over a five
      blink cycle for both the vertical and horizontal meridians: 1) initial lens
      position; 2) settled lens position; 3) amount of lens movement; and 4) rate of
      lens movement. Lower lid position and palpebral aperture height were measured for
      each subject. RESULTS: Graphical analysis showed that a low upper lid position
      and small palpebral aperture promoted superior lens decentration, while a high
      upper lid position and wide palpebral aperature predisposed an individual to
      inferior lens decentration. Significant lid-lens overlap was a common finding
      with high riding lenses in both the initial and settled lens positions. The
      results also suggested that while a rigid lens tended to become more stable as
      the lens center of gravity shifted further behind the corneal apex, this
      gravitational effect was reduced for lenses that interacted with the upper lid.
      CONCLUSIONS: Lid geometry can influence rigid lens centration and stability by
      modifying the effects of lens design and lens mass. We recommend that
      consideration be given to the nature of potential lens-lid interactions prior to
      lens fitting.

PMID- 9001778
TI  - Transvaginal ultrasonographic diagnosis of adenomyosis in female patients
      suffering from uterine fibromatosis.
AB  - Adenomyosis is an underestimated pathology frequently responsible of unknown
      origin pelvic pain and uterine enlargement. It is hyperestrinic condition with
      poor specific symptomatology and preoperative diagnostic tools are very few. The
      most important of them, ultrasound, has improved its diagnostic capacity with the
      introduction of transvaginal way of examination. However, for the ultrasound
      resemblance, the common etiopathogenetic origin and the symptomatologic likeness
      between adenomyosis and uterine leiomyomatosis, a problem still open is the
      differential diagnosis between these two pathologies especially when both are
      present in the same subject. In our study where the preoperative ultrasound was
      followed by surgical finding, we try to give some ultrasonographical guidelines
      to discern among these two pathologic conditions.

PMID- 9001777
TI  - Bausch & Lomb CW 79 aphakic extended wear contact lens: long-term follow-up.
AB  - PURPOSE: The purpose of our study was to assess the long-term tolerance of
      aphakic contact lenses in an elderly male population. METHODS: We conducted a
      follow-up study of Bausch & Lomb CW 79 aphakic extended wear contact lenses fit
      since 1982. A total of 109 patients (115 eyes) were identified. Records of 37
      patients (43 eyes) were available to determine the course of contact lens wear.
      RESULTS: Thirty-six eyes were contact lens dropouts. The average time to failure
      was 22 months. Seventeen eyes from the failure group elected to receive secondary
      intraocular lenses (IOLs). Seven eyes were still wearing CW 79 contact lenses at
      the conclusion of the study. The average length of wear in these seven eyes was
      91 months. CONCLUSIONS: We concluded that the CW 79 aphakic extended wear contact
      lenses were successful in selected cases. However, a high failure rate was found
      on long-term follow-up, and approximately half of the failure were converted to
      secondary IOLs.

PMID- 9001779
TI  - Long-term follow-up of endometriosis after two different therapies (Gestrinone
      and Buserelin).
AB  - OBJECTIVE: To compare the efficacy, tolerance and recurrence rate of
      endometriosis after 5-year follow-up of treatment with Gestrinone and Buserelin,
      respectively. STUDY DESIGN: A prospective study with randomized follow-up of 5
      years duration (minimum) for each patient was done. We included 43 cases of
      endometriosis diagnosed by laparoscopy or laparotomy and treated them with
      Gestrinone (Group G, n = 25 cases) or Buserelin intranasal spray (Group B, n =
      18) for 6 months. RESULTS: General data: Age, height, weight of patients and AFS
      score of endometriosis were without significant differences in either group.
      Specific data: A) Global clinical efficacy was good or excellent in 74% (16/25)
      of group G and in 78% (14/18) of group B without significant differences. B)
      Global clinical tolerance was good in 50% of the patients in group G and in 0% in
      group B (p < 0.001). C) Global evaluation after 5-year follow-up showed "success"
      only for 36% of patients in group G and in 33% in group B (no significant
      differences), with "failure" in 40% and 33%, respectively (no significant
      differences). CONCLUSIONS: 1) Gestrinone and Buserelin intranasal spray are valid
      treatments for the remission of endometriosis, with "success", "failure" and
      "clinical recurrence" rates similar after a follow-up of 5 years of initial
      treatment. 2) The most significant androgenic effect of Gestrinone was the
      presence of acne. Vascular effects were also considered as very undesirable
      effects according to the comments of patients. On the contrary, the effects of
      analogs are generally better tolerated.

PMID- 9001780
TI  - Heterotopic pregnancies in an in-vitro fertilization program.
AB  - During a four-year period in vitro fertilization (IVF) was carried out in 2,356
      cycles. The pregnancy rate per transfer was 24% while the incidence of ectopic
      pregnancies was 7.5% per pregnancy. There were seven cases of heterotopic
      pregnancies-simultaneous intra- and extrauterine pregnancies (1.5% among all IVF
      pregnancies). Two of them were diagnosed after tubal rupture of the ectopic
      pregnancy and five cases were diagnosed by ultrasound at the 7th or 8th week of
      gestation. Laparotomy and subsequent salpingectomy was carried out in six cases
      while in one case the ectopic pregnancy was removed by laparoscopy. Three out of
      the seven heterotopic pregnancies (43%) were successfully continued with normal
      intrauterine embryo development and delivery.

PMID- 9001781
TI  - The influence of obesity in the sexual life of women in menopause. A case control
      study.
AB  - It seemed important to us to investigate sexuality during the post-menopausal and
      senile period to evaluate whether changes in sexual behaviour are related with
      endocrine-functional alterations brought on by menopause, or whether social
      economic and environmental factors represent the principal cause. Thus 1,500
      questionnaires were distributed to women aged from 50 to 87. Of the 1,500
      questionnaires distributed, only 713 (47.53%) were returned completely filled-in.
      All women had been classified for age, civil status and life environment. Our
      statistic analysis does not seem to have singled out those factors that influence
      sexual activity in women of advanced age but shows only how age, indifferently
      from civil status and life environment, represents the most important factor. At
      the same age other factors, probably attached to psychological features and way
      of life and thus difficult to define and even less qualifiable, may be of
      influence, explaining a further percentage of control of those answers not
      explainable by age.

PMID- 9001782
TI  - GnRH analogs in treating uterine leiomyomata and endometriosis.
AB  - The results of hormonal examinations, measurements of dimensions of the uterus
      and leiomyomas, body weight, and also frequency of incurred climacteric signs in
      patients treated with Decapeptyl Depot 3.75 mg for three months are reported.
      Subjects consisted of 12 women, among whom nine were treated for leiomyomas and
      four for endometriosis (one patient also had leiomyomas). Based on examinations
      carried out, the biggest decrease of the uterus and leiomyomas was 13-17%
      observed just after two doses of analog, though after the end of treatment the
      dimensions of the uterus slowly increased. Therefore, 2-month therapy could be
      used successfully as preparation for further conservative surgical treatment.
      Significant increase of body weight in treated patients was not observed. In
      women with endometriosis pain symptoms in the hypogastric area and dyspareunia
      regressed during treatment and at the end were not observed. The disadvantages of
      therapy with Decapeptyl Depot 3.75 was the rapid occurrence of symptoms-
      climacteric signs, especially hot flashes--which were badly tolerated by
      patients. All these symptoms almost totally regressed one month after ending
      therapy.

PMID- 9001783
TI  - EGF/EGF-R system and benign breast disease during and following the treatment of
      gynaecological pathologies with an analogue of LH-RH.
AB  - Clinical and pathological changes of the mammary gland have been studied in 64
      women affected by symptomatic Benign Breast Disease (BBD) coexisting with
      endometriosis or uterine leiomyomata. These patients were rendered hypoestrogenic
      by subcutaneous administration of the LH-RH analogue Goserelin depot [D-ser
      (tBu)6 Aza-Gly10-GnRH (ICI118630)] performed every 28 days, for six months. They
      were evaluated clinically and ultrasonographically before and after treatment to
      find possible changes of BBD as well as of endometriosis or uterine leiomyomata.
      Mammary biopsies were performed before and after treatment in all the patients to
      study the changes of EGF-R expression. Results showed that clinical improvement
      is accompanied with a reduction of EGF-R expression.

PMID- 9001784
TI  - Power Doppler ultrasound: a potentially useful alternative in diagnosing pelvic
      pathologic conditions.
AB  - INTRODUCTION: To evaluate the efficacy of power Doppler sonography in depicting
      soft-tissue hyperemia in endometriosis and other pelvic inflammatory conditions
      thirty-one patients with predominantly pelvic inflammatory symptoms were
      evaluated. MATERIALS AND METHODS: Power Doppler sonography at 5 MHz and a pulse
      repetition frequency of 800 Hz was used. All the women underwent laparoscopy
      after 10 days. RESULTS: Soft-tissue hyperemia was seen on power Doppler sonograms
      in 22 of the symptomatic patients. In these women Doppler demonstrated a diffused
      "blush" of almost or the entire symptomatic sites. Specificity was 52.4%,
      sensitivity 47.1% and the positive predictive value was 53.2%. CONCLUSION: Power
      Doppler sonography showed hyperperfusion in many cases associated with pelvic
      inflammatory pathology. It is a potentially useful adjunct to standard color
      Doppler imaging in depiction of vascular flow.

PMID- 9001785
TI  - NPY and VIP neuropeptides endogenous factors in the induction of preterm delivery
      labour.
AB  - The Authors wanted to verify whether neuropeptides like VIP and NPY have a role
      in regulating the production of PGE2 by the amniotic membrane, by the use of a
      continuous cell line of amniotic derivation as a model of study. The study was
      carried out in the laboratories of the 4th Division of the 2nd Institute of the
      Maternity Home of the Umberto I General Hospital in Rome.

PMID- 9001786
TI  - Histopathological findings of the endometrium in patients with dysfunctional
      uterine bleeding.
AB  - The histopathological examination of the endometrium in cases of abnormal
      functional uterine bleeding frequently reveals the type of functional disturbance
      and assists correct treatment. On this basis, 7,000 endometrial curettages from
      patients with abnormal uterine bleeding were studied. The 1,282 cases with no
      endometrium in phase, organic changes, or systemic disorders were defined as
      dysfunctional uterine bleeding; the endometrial lesions were then classified and
      the histological findings correlated with the patients' ages. The endometrial
      curettages revealed an anovulatory cycle in 984 (77%) of the patients, and an
      ovulatory cycle in 298 (23%). Of the cases with an anovulatory cycle, 446
      patients (47.5%) showed endometrial hyperplasia, 412 (41.86%) showed abnormal
      endometrial proliferation due to prolonged persistence of a follicle, while 106
      (10.77%) showed deficient endometrial proliferation. Three hundred and thirty
      four cases (71.67%) of endometrial hyperplasia were (simple) cystic hyperplasias,
      124 (26.60%) were (complex) adenomatous hyperplasia, and 8 (1.71%) were atypical
      hyperplasia. Of the cases with an ovulatory cycle, 252 (84.56%) showed deficient
      endometrial secretion due to a prolonged proliferative phase, while the other 46
      (15.43%) showed deficient secretion due to luteal phase defect. Seven hundred and
      thirty six patients with an anovulatory cycle and 212 with an ovulatory cycle
      i.e. 948 (74%) of the 1282 patients studied-were at the climacteric. The
      conclusions may be summarised as follows. i) Dysfunctional abnormal uterine
      bleeding was found more often at the climacteric and chiefly in the form of an
      anovulatory endometrium; ii) 88.14% of cases (1130 patients) presented
      histological signs of oestrogen influence in the form of either an anovulatory
      endometrium or an ovulatory endometrium; iii) Cystic (simple) hyperplasia was the
      most common form of endometrial hyperplasia.

PMID- 9001788
TI  - Amniotic fluid embolism (it can present without respiratory manifestations). Case
      report.

PMID- 9001787
TI  - Cirrhosis and pregnancy. A case report and review of the literature.
AB  - A clinical case of a pregnant suffering from hepatic cirrhosis with ascites,
      splenomegaly and portal hypertension is described. The pregnancy carried on till
      the 31st week, even though with the repeated use of tocholytic agents. Cesarean
      section was performed because of the onset of serious jaundice and the decline of
      general maternal conditions. The infant, who had an Apgar score of 8 at the 1st
      and 5th minute, died on the 10th day because of accuse haemorrhagic interstitial
      pneumonitis in premature lungs and hepatopathy associated with widespread
      jaundice. The mother was discharged on the 25th day of the postpartum period, in
      light of the net improvement of her general metabolic condition, the sudden
      regression of the jaundice and the decrease of the cholestasis indices. A review
      of the literature discussing maternal complications fetal risks, management of
      pregnancy and delivery and outcome of the newborn are presented.

PMID- 9001789
TI  - Erythropoietin in the treatment of anaemia in a nephropathic pregnant woman. Case
      report.

PMID- 9001790
TI  - Cervical cerclage in the treatment of cervical incompetence in Zambian women.
AB  - Over a period of 5 years from January 1989 to October 1994, 207 patients with
      cervical incompetence were managed with Mac Donald's cervical cerclage at
      Nkana/Wusikili Mine Hospitals, Kitwe, Zambia. The incidence rate of cervical
      incompetence in our population was 1.47%. Our results confirmed a success rate of
      90.8% as compared to 52.5% in previous pregnancies. This represents 159 (76.8%)
      full term pregnancies, 29 (14%) premature deliveries and 19 (9.2%) abortions.
      Post operation total survival rate was 87.4% with fetal salvage ratio of 1.68. We
      confirmed that optimum time to insert cerclage was 18 weeks and below. The
      possibility of having a mature baby in the group of low number previous abortions
      was significantly higher as compared to the group with a higher number of
      habitual abortions. Better pregnancy outcome was seen in low parity group (less
      than 2 previous deliveries) as compared to higher parity group. Our study
      confirms that cervical cerclage is a successful way in the treatment of cervical
      incompetence.

PMID- 9001791
TI  - Management of patients with intrauterine fetal death.
AB  - Fetal death incidence is 5-10 per 1,000 births. About 25% of the women who carry
      a dead fetus for more than 4 weeks will show significant alterations in their
      coagulation system. The treatment for a patient with endouterine fetal death
      depends on when the pregnancy is terminated, based on the ecographic fetus age.
      There were 15,070 births from January 1983 to December 1994 in Department B of
      the Institute of Obstetrics and Gynecology, University of Torino. We took into
      consideration the cases ofintrauterine fetal death between the 26th and 40th week
      before labour. This study is based on a cohort of 57 cases of intrauterine fetal
      demise from the 24th to the 40th week of pregnancy before spontaneous labour.

PMID- 9001792
TI  - Teratoma of the placenta. A case report.

PMID- 9001793
TI  - Pregnancy and neoplasm are two outstanding examples of natural tolerance to
      homograft.

PMID- 9001794
TI  - DNA testing in familial hypertrophic cardiomyopathy: clinical and laboratory
      implications.
AB  - Counselling and clinical assessment in familial hypertrophic cardiomyopathy (FHC)
      is difficult, particularly in the young, since echocardiographic and ECG changes
      may not be diagnostic and clinical severity can vary. From 1990, when the beta
      cardiac myosin heavy chain gene was implicated in the aetiology of FHC,
      considerable information about the molecular genetics of this disorder has
      emerged. However, an important question facing health professionals is the
      practical significance of DNA testing in FHC. The present study describes a DNA
      based approach to screening for five commonly reported mutations involving the
      beta-cardiac myosin heavy chain gene. Approximately 11% of randomly selected
      families had an abnormality detected.

PMID- 9001795
TI  - Nonsyndromic X-linked mental retardation: review and mapping of MRX29 to Xp21.
AB  - The gene responsible for nonsyndromic mental retardation in a family with 7
      affected males has been localized to Xp21. The maximal two-point lod score was
      3.31 for tight linkage to marker DXS1202 in Xp21.3-p22.3 with crossovers between
      the 3' portion of the DMD gene (DXS1234) proximally and locus DXS989 distally.
      The XLMR gene in this family has been assigned the designation MRX29. The
      localization overlaps with at least six other MRX entities linked to the distal
      short arm of the X chromosome.

PMID- 9001796
TI  - Association of genetic variation at the beta-fibrinogen gene locus and plasma
      fibrinogen levels; interaction between allele frequency of the G/A-455
      polymorphism, age and smoking.
AB  - The beta-fibrinogen G/A-455 polymorphism genotype along with plasma fibrinogen
      levels was determined in 482 healthy middle-aged men, of whom 231 were smokers.
      Smokers had the highest plasma fibrinogen levels (2.92 g/l), ex-smokers the next
      (2.73 g/l), and never-smokers the lowest levels (2.66 g/l, P < 0.001). Those with
      one or two A-455 alleles had significantly higher plasma fibrinogen levels in
      never-smokers and ex-smokers (8.2% and 9.0%, respectively, P < 0.05), and the
      effect was larger in younger men (45 < 55 years, 11.6%, P = 0.002) than older men
      (> 65 years, 4.5%, NS), and was not significant in smokers (2.4%, P > 0.05).
      Allele frequencies were calculated and compared across age groups and between
      smokers and non-smokers. The difference in frequency of the A-455 allele between
      smokers and non-smokers varied significantly with age (P < 0.01), with the
      frequency of the A-455 allele being significantly lower in smokers than in non
      smokers in subjects aged > 65 years (P < 0.05), but not in younger men. This
      demonstrates an interaction between age, smoking and allele frequency of the G/A
      455 polymorphism in this population-based sample.

PMID- 9001797
TI  - DNA polymorphisms in linkage disequilibrium at the 3' end of the human APO AII
      gene: relationships with lipids, apolipoproteins and coronary heart disease.
AB  - Two investigations were undertaken to analyze the 3' region of the apolipoprotein
      AII (Apo AII) gene in patients with myocardial infarction (MI) and controls.
      Previous studies have suggested that a MspI polymorphism in this gene may be
      associated with hypertriglyceridaemia, high levels of HDL cholesterol and Apo
      AII. To verify this hypothesis, the distribution of MspI genotypes and their
      possible associations with several plasma lipid variables were studied in 882
      subjects (411 cases with MI and 471 controls) from the ECTIM study. There were no
      differences in genotype and allele frequencies between cases and controls, and no
      differences in lipid variable levels in controls carrying the less frequent MspI
      allele vs other controls. Using single-strand conformation polymorphism (SSCP)
      analysis, we detected a new polymorphism which caused by a C-to-T transition
      located in the third intron near the splice junction site (acceptor). This
      polymorphism modifies a Bst N1 restriction site. The ECTIM population was
      screened for this new marker, and no significant associations with MI and plasma
      lipid levels were found. Our results suggest that these two variants located in
      the coding region of the Apo AII gene are unlikely to contribute significantly to
      the level of plasma lipid variables and the risk of coronary heart disease (CHD)
      in the European population.

PMID- 9001799
TI  - Rapid detection of a mutation hot-spot in the human androgen receptor.
AB  - Mutations of the human androgen receptor gene may disturb sexual development in
      males, and are inherited as an X-linked recessive trait. The vast majority of the
      mutations are familial. We have identified a large kindred with complete androgen
      insensitivity syndrome (CAIS) without detectable androgen-binding in genital skin
      fibroblasts. A single nucleotide substitution (C-to-T transition) was identified,
      resulting in an Arg855 to Cys in the androgen binding domain. To date, four
      independent CAIS families have been reported with this specific mutation that
      coincides with the propensity of cytosines at CpG dinucleotides to methylate. An
      allele-specific oligo-nucleotide assay was developed that allowed for the rapid
      and specific identification of this mutation hot-spot in individuals with
      androgen receptor insensitivity syndromes.

PMID- 9001798
TI  - Reduction of CAG expansions in cerebellar cortex and spinal cord of DRPLA.
AB  - Recent studies have identified an unstable expansion of a CAG repeat in a gene
      located on chromosome 12 as a cause of dentatorubropallidoluysian atrophy
      (DRPLA). To investigate whether the somatic heterogeneity may relate to the
      selective neuronal damage caused by the disease, genomic DNA from various tissues
      of an autopsied patient with DRPLA was examined to compare possible variations of
      expanded CAG repeats for the disease. Although the size of the expanded CAG
      repeat from many organs was almost the same as that from peripheral lymphocytes,
      those from cerebellar cortex and spinal cord were unexpectedly reduced and
      numbers of peaks within an expanded allele were relatively strict. These results
      suggest that the CAG repeat is not simply expanded in the genome of the tissues
      that are most involved in DRPLA, but that another mechanism might be responsible
      for the specific neuronal death.

PMID- 9001800
TI  - Genetic analysis of the glucose-6-phosphatase mutation of type 1a glycogen
      storage disease in a Chinese family.
AB  - Type 1a glycogen storage disease (GSD) is an autosomal recessive metabolic
      disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Polymerase
      chain reaction (PCR) and nucleotide sequence analysis were used to identify the
      location and nature of mutations at the G6Pase locus in two siblings affected
      with type 1a GSD. Both patients are compound heterozygotes with two different
      single nucleotide substitutions in the two G6Pase alleles. A guanine to adenine
      transition was identified at base position 327 in the exon 2, converting an
      arginine to a histidine at codon 83. The second substitution was a thymine to
      adenine transversion at base position 1101 in the exon 5, converting an
      isoleucine to an asparagine at codon 341. Family study reveals that both parents
      are heterozygous carriers: the father with a mutant G6Pase allele at exon 2, the
      mother with another mutant G6Pase allele at exon 5. This is the first family
      study in Taiwan on type 1a GSD identified by molecular analysis. The mutations
      identified herein are novel substitutions in the G6Pase gene. In addition, an
      adenine to guanine substitution was observed at base position 653 in the exon 5
      of G6Pase gene in both sibling patients and their parents, as well as in 15
      normal Chinese subjects and three normal Caucasian subjects.

PMID- 9001801
TI  - Distinct facial appearance with nasal hypoplasia, constipation, severe mental
      retardation and hypotonia in two unrelated young males.
AB  - In this report we describe two unrelated young males with severe mental
      retardation, persisting hypotonia, and constipation. A maternal uncle of one of
      these two boys died at the age of 18 months and presented the same clinical
      symptoms. The triad mental retardation, hypotonia, constipation is a
      characteristic finding in the FG syndrome, an X-linked mental retardation
      syndrome. At the present time, there is increasing evidence that the FG syndrome
      phenotype may be present in different XLMR conditions, e.g. the fragile X
      syndrome. In addition to the triad severe mental retardation, hypotonia,
      constipation, the present two male index patients had a characteristic facial
      appearance with nasal hypoplasia, relative microcephaly and pre- and postnatal
      overgrowth. The question is raised whether the present two males are examples of
      a specific entity within the FG-syndrome-like phenotype.

PMID- 9001802
TI  - The Floating-Harbor syndrome: two affected siblings in a family.
AB  - In this report we describe two siblings with pre- and postnatal growth
      retardation and clinical signs and symptoms most compatible with the diagnosis of
      Floating-Harbor syndrome. The oldest sibling, a girl, died in the first year of
      life from recurrent infections. The younger sibling, a male, is now 16.5 years
      old and mildly mentally retarded.

PMID- 9001803
TI  - Partial monosomy 10q and partial trisomy 9q with anal atresia due to maternal
      translocation: t(9;10)(q32;q26).
AB  - We report a case of a boy with a partial deletion of the long arm of chromosome
      10 and partial duplication of the long arm of chromosome 9 due to maternal
      balanced translocation. The karyotype was 46,XY,-10, +der(10)t(9;10)(q32;q26)mat.
      Our patient had imperforate anus and as this finding is usually not observed in
      association with trisomy 9q, it suggests that partial monosomy of the long arm of
      chromosome 10 might be associated with anogenital anomalies.

PMID- 9001804
TI  - Keipert syndrome in two brothers from Turkey.
AB  - Two brothers, 17 and 21 years of age, with depressed nasal bridge, prominent
      frontal bones, hypoplastic maxilla, mild sensorineural hearing loss, broad
      terminal phalanges and mild pulmonary stenosis are presented. These findings are
      similar to those of the syndrome described by Keipert et al. in 1973. To the best
      of our knowledge, this is only the second report of this syndrome.

PMID- 9001806
TI  - Down syndrome associated with a retroperitoneal teratoma and Morgagni hernia.
AB  - Down syndrome may be associated with many complications. Among the malignancies
      associated with Down syndrome, leukaemia is the most common. This is a case
      report of a patient with Down syndrome associated with both a retroperitoneal
      teratoma and a Morgagni hernia.

PMID- 9001805
TI  - Three familial cases presenting with an immobile spine. Rigid spine or Emery
      Dreifuss syndrome?
AB  - A father and his two sons presented with slowly progressive muscular weakness,
      contractures of the spine, elbows and ankles, and cardiac conduction disturbances
      in the father. Clinical and histological findings are discussed in relation to
      the hitherto reported cases of autosomal dominant variant of the Emery-Dreifuss
      syndrome and the distinction from the rigid spine syndrome.

PMID- 9001807
TI  - Siblings with congenital renal tubular acidosis and nerve deafness.
AB  - Two siblings (a boy and a girl) had congenital renal tubular acidosis (RTA) with
      nephrocalcinosis. Hearing loss due to nerve deafness was diagnosed at 13 1/2 and
      9 years of age, respectively. The parents, who are second cousins, are healthy.
      They have another boy who is unaffected. This is in accordance with an autosomal
      recessive gene. The association of RTA and deafness was first noted by Royer in
      1967, and so far some 50 cases have been described. The literature is reviewed.

PMID- 9001808
TI  - COFS syndrome with familial 1;16 translocation.
AB  - We report on an Egyptian girl with phenotypic abnormalities of cerebro-oculofacio
      skeletal syndrome. She had microcephaly, bilateral congenital cataract,
      nystagmus, long ear pinnae, camptodactyly, prominent heels, coxa valga, kyphosis
      and flexure contracture of the elbows and knees. CT scan showed bilateral
      symmetrical intracranial calcifications. In addition, she had an apparently
      balanced translocation: 46,XX,t(1;16)(q23;q13) in all cells transmitted from a
      phenotypically normal mother with a similar balanced translocation mosaicism. We
      suggest that genes for COFS syndrome could be located on chromosome 1q23 or
      16q13. We recommend chromosomal analysis and DNA studies in cases with COFS
      manifestations.

PMID- 9001809
TI  - Life-threatening cardiac involvement throughout life in a case of Costello
      syndrome.
AB  - Costello syndrome is characterized by poor postnatal growth, mental retardation,
      curly hair, coarse face, loose skin of the hands and feet, and nasal papillomata.
      Patients with Costello syndrome have a high incidence of cardiac involvement,
      such as arrhythmias, hypertrophic cardiomyopathy, or congenital anomalies. The
      importance of cardiac involvement in Costello syndrome has not been strongly
      emphasized thus far, although arrhythmia and hypertrophic cardiomyopathy are both
      serious forms of cardiac involvement. We report the case of a Japanese girl with
      Costello syndrome, who experienced life-threatening cardiac involvement
      throughout her life.

PMID- 9001810
TI  - A case report of 46,XX,del(21)(q22) de novo deletion associated with Imerslund
      Grasbeck syndrome.
AB  - We describe a 2-year-old female patient who had megaloblastic anaemia caused by
      selective vitamin B12 malabsorption (Imerslund-Grasbeck syndrome) and
      del(21)(q22). To our knowledge, this is the first observation of Imerslund
      Grasbeck syndrome associated with del(21)(q22) in the literature.

PMID- 9001811
TI  - Nosology of fetal hypokinesia sequence based on CNS abnormalities: is there an
      Aase-Smith syndrome?
AB  - Aase-Smith syndrome (ASS) is usually defined as a dominantly inherited
      combination of arthrogryposis, Dandy-Walker malformation and cleft palate. We
      describe a sporadic case of foetal akinesia with abnormal fossa posterior,
      fitting the diagnosis of ASS, and discuss the nosology of this entity among
      syndromes with distal arthrogryposis. ASS shows a "hybrid" phenotype: adults with
      mild ASS could be classified as distal arthrogryposis, whereas severely affected
      newborns overlap with the Marden-Walker phenotype, which is recessively
      inherited. The specificity of the disorder comes from the coexistence of both
      forms in the same pedigree, so that ASS appears impossible to diagnose with
      certitude in sporadic cases. We suggest that the severe expression of ASS is only
      the extreme but aspecific expression of a dominantly inherited form of distal
      arthrogryposis. Implications for genetic counselling in distal arthrogryposis are
      outlined.

PMID- 9001812
TI  - Desbuquois syndrome in an Arab Bedouin family.
AB  - We report a consanguineous Arab Bedouin family with Desbuquois syndrome, an AR
      syndrome of a midface hypoplasia and joint laxity. We believe this is the first
      report of this syndrome in Arab Bedouins.

PMID- 9001813
TI  - Further evidence for a syndrome of "apple peel" intestinal atresia, ocular
      anomalies and microcephaly.
AB  - We report on a male child with "apple peel" atresia, associated with
      microcephaly, with subsequent hydrocephalus, short stature, moderate global
      developmental delay and ocular abnormalities. A similar phenotype was previously
      reported by Stromme et al. in 1993 in female siblings, and this description of
      another affected individual provides further evidence for this being a distinct
      syndromic entity.

PMID- 9001814
TI  - Mild form of beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA thiolase
      deficiency) in two Japanese siblings: identification of detectable residual
      activity and cross-reactive material in EB-transformed lymphocytes.
AB  - Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is an inherited metabolic
      disorder of isoleucine and ketone body catabolism. We report the cases of two
      siblings who showed clinically mild forms of this disorder. They did not excrete
      tiglylglycine in urine. Their EB-transformed lymphocytes contained residual T2
      activity, which was confirmed by immunotitration analysis. In immunoblot
      analysis, the bands corresponding to T2 in the samples of the cell lines from two
      patients were the most intensely detected among those from 19 T2-deficient cell
      lines tested.

PMID- 9001815
TI  - FISH characterization of the Xq21 breakpoint in a translocation carrier with
      premature ovarian failure.
AB  - A panel of ordered YAC clones, isolated using STSs in the Xq13-Xq23 region, was
      used to characterize by Fluorescent In Situ Hybridization (FISH) the Xq21
      breakpoint in a t(X;1)(q21;p34) translocation female with premature ovarian
      failure. The YAC 949E11 was found to span the breakpoint, but also to join the
      two non-overlapping YACs 36CB1 and 40AB3, proximal and distal, respectively, to
      the patient's Xq21 breakpoint.

PMID- 9001816
TI  - Familial translocation (X;3)(p22.3;p23): chromosomal in situ suppression (CISS)
      hybridization and inactivation pattern study.

PMID- 9001817
TI  - Clinical features in the Wiedemann-Beckwith syndrome.

PMID- 9001818
TI  - Predictive and preimplantation genetic testing for Huntington's disease and other
      late onset dominant disorders: not in conflict but complementary.

PMID- 9001819
TI  - Antley-Bixler syndrome.

PMID- 9001820
TI  - Congenital heart defect and conductive hypoacusia in a patient with the KBG
      syndrome.

PMID- 9001821
TI  - A review of long-term studies evaluating the efficacy of weight loss in
      ameliorating disorders associated with obesity.
AB  - Obesity leads to and exacerbates many serious disorders, including hypertension,
      dyslipidemia, cardiovascular disease, non-insulin-dependent diabetes mellitus,
      gallbladder disease, respiratory dysfunction, gout, and osteoarthritis. Many
      short-term studies have shown that weight loss can ameliorate or, in some cases,
      reverse such disorders. Fewer long-term studies-defined as those whose combined
      acute intervention and follow-up phases extend for at least 1 year-of the
      therapeutic benefits of weight loss on specific disorders have been undertaken.
      Those long-term studies that have been performed tend to confirm the results of
      briefer studies. Even when weight loss has been comparatively modest or some
      degree of weight regain has occurred, weight loss is generally associated with a
      decrease in risk factors and the alleviation of clinical symptoms.

PMID- 9001822
TI  - Treatment regimens for patients with toxoplasmic encephalitis.
AB  - Toxoplasma gondii is an obligate intracellular parasitic protozoan that infects a
      variety of warm-blooded animals, including humans. Infection is usually
      asymptomatic in immunocompetent individuals but may be devastating in
      immunocompromised individuals such as those with acquired immunodeficiency
      syndrome (AIDS). Clinical manifestations of infection in immunocompromised
      patients include the development of encephalitis. It has been estimated that
      approximately 30% of patients with AIDS who are latently infected will eventually
      develop toxoplasmic encephalitis. The most common regimen used to treat
      toxoplasmic encephalitis is a combination of pyrimethamine 50 to 100 mg/d and
      sulfadiazine 4 to 8 g/d, with or without folinic acid 10 mg/d. This regimen,
      however, commonly leads to adverse effects or relapses. Other pharmacologic
      approaches include the use of clindamycin rather than sulfadiazine, the macrolide
      antibiotics, atovaquone, 5-fluorouracil, trimethoprim/sulfamethoxazole,
      minocycline or doxycycline, trimetrexate with folinic acid, dapsone, rifabutin,
      pentamidine, and diclazuril. None of these alternative regimens has been proven
      to be more effective than the standard pharmacologic therapy. An evolving
      approach is the use of immunotherapy, such as interleukin-2, -6, and -12;
      interferon-gamma; and alpha-tumor necrosis factor. Restoring a competent immune
      system may be the only cure for toxoplasmosis and other opportunistic infections.

PMID- 9001823
TI  - The angiotensin II type 1 receptor blocker losartan in clinical practice: a
      review.
AB  - Blockade of angiotensin II receptors was first achieved in the 1970s using a
      peptide, saralasin acetate. Although it was effective in lowering blood pressure,
      it required parenteral administration and had a short duration of action and
      partial agonist activity. These disadvantages are absent with losartan, a
      selective, orally administered, nonpeptide blocker of the angiotensin II type 1
      receptor that recently became available for clinical use. Losartan has a
      sustained duration of action, permitting once-daily dosing in many patients, and
      lacks partial agonist activity. More than 3300 hypertensive patients have
      received losartan in Phase III, controlled clinical trials. Losartan given
      concomitantly with a low dose (12.5 mg) of hydrochlorothiazide further reduces
      blood pressure. Its overall incidence of adverse experiences is similar to that
      of placebo. Because of its efficacy, specificity, duration of action, and safety
      profile, losartan should be considered as first-line therapy for the treatment of
      patients with hypertension.

PMID- 9001824
TI  - Use of Broncho-Vaxom in private practice: phase IV trial in 587 children.
AB  - We conducted a Phase IV, open-label clinical trial to test the efficacy and
      safety of the immunomodulating agent Broncho-Vaxom in private practice. The trial
      comprised 587 children younger than 12 years of age who had an acute respiratory
      tract infection at entry and a history of recurrent respiratory tract infections.
      The patients were given one capsule daily, 10 days per month, for 3 consecutive
      months. During the acute phase of the disease the patients also received
      antibiotic therapy. Comparing the infection present at entry with previous
      infections, the time to improvement (mean +/- SD) decreased from 6.77 +/- 4.42
      days to 3.76 +/- 2.18 days, while the time to cure decreased from 11.86 +/- 8.41
      days to 7.36 +/- 4.93 days. During the 3 months of therapy, the number of
      infections decreased from 1.79 +/- 0.96 1 month before treatment to 0.24 +/- 0.46
      in the third month of treatment; absenteeism decreased from 3.17 +/- 3.07 days to
      0.16 +/- 0.63 days; and the number of antibiotic treatments decreased from 1.71
      +/- 1.06 to 0.16 +/- 0.51. In the patients who experienced a recurrent
      respiratory tract infection during the study, the time to improvement decreased
      from 5.46 +/- 3.28 days before treatment to 2.79 +/- 1.36 days after treatment,
      and the time to cure decreased from 8.71 +/- 3.96 days to 4.54 +/- 2.26 days.
      Adverse events included asthenia and adynamia in 3 patients, diarrhea in 3, rash
      in 2, fever in 2, exacerbation of symptoms in 2, adenitis in 1, and flulike
      syndrome in 1. We conclude that Broncho-Vaxom is effective and safe for the
      treatment of acute episodes of respiratory tract infections and for preventing
      recurrences.

PMID- 9001826
TI  - Double-masked, multicenter study of an estradiol matrix transdermal delivery
      system (Alora) versus placebo in postmenopausal women experiencing menopausal
      symptoms. Alora Study Group.
AB  - This 12-week, double-masked, double-dummy, randomized, parallel-group study
      compared the efficacy and safety of an estradiol matrix transdermal delivery
      system (Alora) in two strengths (50-microgram/d estradiol and 100-microgram/d
      estradiol) with placebo in postmenopausal women who were experiencing at least 60
      moderate-to-severe hot flushes per week. In 273 postmenopausal women, the
      reduction in the frequency of moderate-to-severe hot flushes was significantly
      better than placebo within 2 weeks of initiating therapy in the 100-microgram/d
      group and within 3 weeks of initiating therapy in the 50-microgram/d group. The
      reduction in hot flushes for both active treatment groups remained significantly
      different from placebo throughout the 12-week trial. Improvement in vaginal
      cytology profile (maturation index) was observed in both active treatment groups.
      Serum estradiol concentrations were elevated to early-to mid-follicular levels,
      in proportion to dose, and the estradiol/estrone ratio remained within the
      expected premenopausal range. The incidence of estrogen-related side effects was
      modest but greater in the active treatment groups than in the placebo group:
      Breast pain was reported in 4.5% of the patients in the 50-microgram/d group,
      5.3% of patients in the 100-microgram/d group, and none of the patients in the
      placebo group. Breakthrough bleeding occurred in 3.4% of women in the 50
      microgram/d group, 20.2% of women in the 100-microgram/d group, and 4.4% of women
      in the placebo group. Only 3 (1.1%) patients terminated treatment because of skin
      reactions. This study demonstrates that this estradiol matrix transdermal
      delivery system is effective in the treatment of menopausal symptoms, while
      providing the skin tolerability desired by patients.

PMID- 9001825
TI  - Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of action and
      comparison with zidovudine.
AB  - We have previously described the inhibition of human immunodeficiency virus
      serotype 1 (HIV-1) using the antimalarial hydroxychloroquine (HCQ), a weak base
      that inhibits the posttranslational modification of glycoprotein 120 (gp 120) in
      T cells and monocytes. The mechanism of inhibition of gp 120 production was
      presumed to be the ability of HCQ to increase endosomal pH and therefore alter
      enzymes required for gp120 production. To further clarify this action, we have
      determined the effect of HCQ and its enantiomers on endosomal pH. Pretreatment of
      cells with HCQ and the levo- and dextro-enantiomers at concentrations
      demonstrated to suppress anti-HIV-1 activity increased endosomal pH to levels
      similar to increases seen with chloroquine and ammonium chloride, two other weak
      bases, and decreased gp 120 production. The dextro- and levo-enantiomers
      suppressed HIV-1 replication to a similar extent and were no more toxic than
      racemic HCQ. We next compared the anti-HIV-1 effect of HCQ with zidovudine (ZDV)
      in both newly and chronically HIV-1-infected T-cell and monocytic cell lines (63
      and 63HIV). HCQ suppressed HIV-1 replication in a dose-dependent manner in both
      recently and chronically infected T-cell and monocytic cell lines. In contrast,
      ZDV pretreatment had potent anti-HIV-1 activity in the newly infected T and
      monocytic cells but not in chronically infected cells. An additive effect of HCQ
      with ZDV was observed in the newly infected T and monocytic cells but not in the
      chronically infected cells. Although the anti-HIV-1 effect of HCQ was less than
      that of ZDV, HCQ may still be potentially useful either as an alternative HIV-1
      treatment or in combination with other anti-HIV-1 agents, especially in patients
      who have rheumatic manifestations of HIV-1 infection.

PMID- 9001827
TI  - The efficacy of fluticasone propionate aqueous nasal spray for allergic rhinitis
      and its relationship to topical effects.
AB  - Fluticasone propionate aqueous nasal spray is an intranasal corticosteroid for
      the treatment of patients with allergic rhinitis. This double-masked, double
      dummy, parallel-group study was conducted to confirm that the efficacy of
      fluticasone propionate nasal spray is attributable to topical rather than
      systemic effects. A total of 304 patients with documented seasonal allergic
      rhinitis were randomly assigned to receive fluticasone propionate nasal spray 200
      micrograms once daily (n = 77), oral fluticasone propionate 5 mg once daily (n =
      73), oral fluticasone propionate 10 mg once daily (n = 77), or placebo (n = 77)
      for 14 days. Plasma fluticasone propionate concentrations were determined at
      baseline and after 14 days of treatment (day 15). Nasal symptoms were recorded
      daily by patients and assessed weekly by clinicians. On day 15, more patients in
      the oral fluticasone propionate 5-mg or 10-mg groups, compared with patients in
      the fluticasone propionate nasal spray group or the placebo group, had detectable
      plasma fluticasone propionate concentrations, and mean concentrations were higher
      in the oral fluticasone propionate groups. Both clinician- and patient-rated
      total and individual nasal symptom scores for obstruction, rhinorrhea, sneezing,
      and itching were significantly lower in the fluticasone propionate nasal spray
      group compared with either of the oral fluticasone propionate groups or the
      placebo group. With few exceptions, oral fluticasone propionate (5 mg or 10 mg)
      was not significantly different from placebo on any measures of efficacy. These
      findings indicate that the efficacy of fluticasone propionate nasal spray (200
      micrograms once daily) in the treatment of allergic rhinitis results from direct
      topical effects rather than from indirect effects after systemic absorption.

PMID- 9001829
TI  - Clinical efficacy of dirithromycin in patients with bacteremic pneumonia.
AB  - Dirithromycin is a new macrolide antimicrobial drug with a long half-life (44
      hours) that reaches high tissue concentrations, thus permitting once-daily oral
      dosing and shorter courses of therapy. Soon after absorption, dirithromycin
      enters the tissue so rapidly that serum concentrations are comparatively low. It
      could be hypothesized that these low serum levels could endanger the outcome in
      patients with bacteremic pneumonia. We reviewed the database on dirithromycin
      pneumonia (consisting of 1108 patients randomized to receive dirithromycin or
      erythromycin in two double-masked trials) to ascertain its efficacy in patients
      with community-acquired pneumonia and concomitant bacteremia. Fourteen (2.5%) of
      555 dirithromycin-treated patients and 10 (1.8%) of 553 erythromycin-treated
      patients had bacteremia. A favorable clinical response posttherapy was observed
      in 92.3% and 88.9% of these patients with a response assigned, respectively.
      Overall, favorable response rates were comparable between the two groups in the
      bacteremic subsets: patients with pneumococcal bacteremia, patients with
      nonbacteremic pneumococcal pneumonia, and all patients enrolled with acute
      pneumonia who had a posttherapy clinical response. In the treatment of patients
      with mild or moderate community-acquired pneumonia, including those with
      unsuspected and incidental bacteremia, dirithromycin is an effective macrolide
      antimicrobial drug.

PMID- 9001828
TI  - The impact of different therapies on symptoms of benign prostatic hyperplasia: a
      prospective study.
AB  - We conducted an observational study to evaluate prospectively the effectiveness
      of four modes of treatment for benign prostatic hyperplasia (BPH)-watchful
      waiting, alpha-blocker therapy, finasteride therapy, and surgery (transurethral
      prostatectomy). A total of 1459 men aged 48 to 84 years, who were diagnosed for
      the first time by physicians as having BPH in 1994 and who had not received
      treatment, participated in the study. During 1 year of follow-up, 1064 (72.9%)
      men remained on no treatment (watchful waiting), 156 (10.7%) were treated with
      finasteride, 198 (13.6%) were treated with an alpha-blocker, and 41 (2.8%)
      underwent prostatectomy. The American Urological Association (AUA) Symptom Index
      was administered to the cohort before the initiation of treatment in 1994, as
      well as 1 year later. Improvements in lower urinary tract symptoms, as measured
      by the AUA Symptom Index, were assessed using linear and logistic regression,
      adjusting for age and baseline. Men who underwent prostatectomy reported the
      biggest improvements in lower urinary tract symptoms, whether assessed by mean
      changes in symptom scores relative to no treatment (-5.44; 95% confidence
      interval [CI]-6.91 to -3.97) or by the odds of improving by 5 or more points on
      the AUA Symptom Index (odds ratio, 12.66; 95% CI, 5.93 to 27.0). Irrespective of
      the initial degree of symptom severity, prostate surgery resulted in larger
      improvements than those reported for either finasteride or alpha-blocker therapy.
      In this prospective, observational study, prostatic surgery was associated with
      statistically and clinically significant improvements in BPH symptoms.

PMID- 9001830
TI  - Comparative bioavailability of ceftibuten in capsule and suspension forms.
AB  - The comparative bioavailability of ceftibuten, a new third-generation
      cephalosporin antibiotic given orally once daily, in capsule and suspension
      dosage forms, was assessed in healthy male subjects. In three separate studies,
      subjects received either a 400-mg dose as a suspension or one laboratory-batch,
      400-mg capsule; one laboratory-batch, 400-mg capsule or two laboratory-batch, 200
      mg capsules; or one production-batch, 400-mg capsule or two laboratory-batch, 200
      mg capsules. Plasma samples were assayed for ceftibuten using high-performance
      liquid chromatography, and the data were assessed using pharmacokinetic and
      statistical methods. Confidence intervals for the maximum plasma concentration
      and the area under the plasma concentration-time curve extrapolated to infinity
      were within 80% to 125% of guidelines, demonstrating the bioequivalence of the
      two treatments within each of the three studies. One 400-mg capsule (laboratory
      or production batch) was bioequivalent to two 200-mg capsules used in a clinical
      efficacy trial; the 400-mg suspension was bioequivalent to a 400-mg capsule
      (laboratory batch). Thus we concluded that the capsule and the suspension dosage
      forms were bioequivalent.

PMID- 9001831
TI  - Ranitidine versus cimetidine in the healing of erosive esophagitis.
AB  - Ranitidine 150 mg twice daily (BID) is an approved therapeutic approach for
      relieving the symptoms of gastroesophageal reflux disease. Ranitidine 150 mg four
      times daily (QID) and cimetidine 800 mg BID are indicated for endoscopically
      diagnosed erosive esophagitis. This 12-week, randomized, multicenter trial
      involving 696 patients compared ranitidine 150 mg BID and ranitidine 150 mg QID
      with cimetidine 800 mg BID in healing erosive esophagitis. Healing rates, as
      determined by endoscopy, at 4, 8, and 12 weeks were comparable with ranitidine
      150 mg BID (38%, 56%, and 71%, respectively) and cimetidine 800 mg BID (37%, 52%,
      and 68%, respectively), as were reductions in heartburn frequency and antacid
      consumption. However, ranitidine 150 mg QID produced significantly higher healing
      rates (49%, 67%, and 77%, respectively) and greater reductions in heartburn
      frequency and antacid consumption than cimetidine 800 mg BID. All treatment
      regimens were well tolerated. Thus ranitidine 150 mg BID is as effective as
      cimetidine 800 mg BID, and ranitidine 150 mg QID is more effective than
      cimetidine 800 mg BID in healing erosive esophagitis and reducing heartburn
      frequency and antacid consumption.

PMID- 9001832
TI  - An open-label, noncomparative, multicenter study of ramipril in the treatment of
      patients with mild-to-moderate hypertension.
AB  - Ramipril, a once-a-day angiotensin-converting enzyme inhibitor, was studied in
      the treatment of mild-to-moderate hypertension in 240 patients. A total of 194
      patients (111 women and 83 men; mean +/- SD age, 46.0 +/- 11.5 years) were
      considered assessable for study. After a 2-week placebo washout phase, all
      patients received ramipril 2.5 mg once daily for 4 weeks. At 4 weeks, blood
      pressure was evaluated for response to therapy. Responders to 2.5 mg were
      continued on the same dose; nonresponders received 5 mg once daily for another 4
      weeks. Results showed that 91% of patients responded after 8 weeks of therapy,
      60% to 2.5 mg and 31% to 5 mg. Ramipril was well tolerated and, because of its
      long half-life, can be considered a true once-a-day angiotensin-converting enzyme
      inhibitor for the treatment of patients with mild-to-moderate hypertension.

PMID- 9001833
TI  - Comparison of electromotive drug administration with ketorolac or with placebo in
      patients with pain from rheumatic disease: a double-masked study.
AB  - This study was undertaken to assess the efficacy of ketorolac compared with
      placebo when delivered by electromotive drug administration (EMDA) in patients
      with pain from rheumatic disease. In EMDA, or iontophoresis, a low-intensity
      electric current is applied over the skin to deliver medication into body
      tissues. Although EMDA has been used to treat patients with various diseases,
      controlled studies are lacking in patients with rheumatic disease. This double
      masked study included 60 patients (43 women and 17 men) aged 31 to 80 years with
      the following conditions: 12, epicondylitis; 30, scapulohumeral periarthritis;
      10, gonalgia; and 8, metatarsalgia. They were divided randomly by a physician
      into 2 groups of 30 patients each for 5 sessions of active treatment (30 mg of
      ketorolac) or placebo (5 mL of normal saline). Treatment took place every other
      day for 20 minutes. Immediately before and after the five treatment sessions and
      7 days after treatment ended, both patient and physician measured the degree of
      pain using a categoric scale (no pain, slight pain, intermediate pain, strong
      pain, and very strong pain) and evaluated pain intensity using the Scott and
      Huskisson Visual Analogue Scale (VAS). Seven days after treatment ended, both
      physician and patient judged the result of treatment using a second categoric
      scale (no improvement or intermediate, good, or very good result). Both ketorolac
      and placebo provided immediate, significant pain relief when delivered by EMDA,
      but only those patients receiving ketorolac experienced a further reduction in
      pain 7 days after treatment; those receiving placebo experienced a slight
      increase in pain. VAS values differed significantly between the two groups. Poor
      results (no improvement) were significantly higher in the placebo-treated group,
      while good results were significantly higher in the ketorolac-treated group. No
      patient reported any adverse effects during treatment. This study demonstrates
      that ketorolac relieves pain when delivered by EMDA and offers longer-lasting
      pain relief than does placebo.

PMID- 9001834
TI  - Effectiveness of ranitidine 150 mg at bedtime as maintenance therapy for healed
      gastric ulcers.
AB  - As many as 89% of gastric ulcer patients experience ulcer recurrences within 1
      year of successful healing with conventional antiulcer therapies. Because
      ranitidine is effective in the healing of gastric and duodenal ulcers and the
      maintenance of healed duodenal ulcers, we hypothesized that ranitidine would also
      be effective in the maintenance of healed gastric ulcers. A 48-week, placebo
      controlled, randomized, double-blind, multicenter trial was conducted to compare
      ranitidine 150 mg administered at bedtime with placebo for the maintenance of
      healed gastric ulcers. Endoscopies were performed at baseline and repeated after
      12, 24, 36, and 48 weeks of treatment. Gastric ulcer recurrence rates at each
      scheduled endoscopy were significantly lower in patients receiving ranitidine
      (5%, 13%, 16%, and 19%, respectively) compared with those receiving placebo (20%,
      30%, 40%, and 50%, respectively). Compared with placebo, ranitidine was more
      effective in maintaining healed gastric ulcers regardless of previous gastric
      ulcer history, smoking status, age (< 65 vs > or = 65 years), or sex. There were
      no significant differences between the two treatment groups in the number of
      patients experiencing adverse events or laboratory abnormalities. Ranitidine 150
      mg administered at bedtime provides safe and effective treatment for the
      maintenance of healed gastric ulcers.

PMID- 9001835
TI  - Pilot study of oral polymeric N-acetyl-D-glucosamine as a potential treatment for
      patients with osteoarthritis.
AB  - Glucosamine and its derivatives, such as glucosamine sulfate and N-acetyl-D
      glucosamine (NAG), have been shown to be effective in the treatment of patients
      with osteoarthritis. Unfortunately, the half-life of glucosamine in the blood is
      relatively short; therefore, a sustained-release form of the compound would be
      highly desirable. The purpose of this pilot study was to determine whether the
      polymeric form of NAG (POLY-Nag) could provide a longer-lasting oral source of
      NAG. Ten healthy subjects each ingested 1 g/d of either NAG or POLY-Nag for 3
      days. After a 4-day washout period, each subject was crossed over to receive the
      other compound for 3 days. Serum samples were collected and analyzed using high
      performance liquid chromatography. Results show that orally ingested NAG and POLY
      Nag are absorbed, resulting in increased serum levels of NAG, and POLY-Nag
      appears to be at least as effective as NAG. Serum levels of NAG had decreased by
      48 hours after cessation of ingestion of NAG or POLY-Nag but were still above
      baseline levels. Increases in serum glucosamine levels indicate that NAG and POLY
      Nag are converted to glucosamine in vivo. In conclusion, POLY-Nag may provide a
      source of serum glucosamine for treatment of patients with osteoarthritis. Longer
      and more rigorous pharmaco-kinetic and clinical studies need to be done.

PMID- 9001836
TI  - Evaluating the safety of mibefradil, a selective T-type calcium antagonist, in
      patients with chronic congestive heart failure.
AB  - Mibefradil is a novel calcium antagonist belonging to a new chemical class of
      benzimidazolyl-substituted tetraline derivatives. The safety of mibefradil in
      patients with mild-to-moderate chronic congestive heart failure (CHF) due to
      coronary heart disease was assessed in a randomized, double-masked, placebo
      controlled, multiple-ascending-dose trial in 45 patients. Patients were assigned
      to receive one of five dose levels (6.25, 12.5, 25, 50, or 100 mg/d) of
      mibefradil or placebo according to a randomization list. If safety variables
      remained stable, the subsequent group of patients was randomized to the next
      higher dose. The safety variables assessed included New York Heart Association
      class, vital signs, and ejection fraction. Patients were evaluated at baseline
      and day 8 of the dosing period. Mibefradil did not worsen clinical or cardiac
      variables. Approximately 23.3% (7 of 30) of the mibefradil-treated patients
      reported one or more adverse events compared with 13.3% (2 of 15) of the placebo
      group. The incidence of adverse events was not dose dependent. In summary, short
      term oral dosing of mibefradil did not worsen measures of cardiac function in 30
      patients with mild-to-moderate CHF.

PMID- 9001837
TI  - Roxatidine versus ranitidine in the treatment of patients with duodenal ulcer: a
      randomized, double-masked, multicenter study.
AB  - The comparative efficacy of roxatidine and ranitidine in the treatment of
      patients with acute duodenal ulcer was assessed at 4 and 6 weeks in this
      multicenter study. Ninety-four of 192 patients were given roxatidine in a single
      nightly dose of 150 mg, and 98 patients were given ranitidine in a single nightly
      dose of 300 mg. All the patients had endoscopically proven duodenal ulcer. Of the
      171 assessable patients, ulcers were healed in 88% of the roxatidine group (73 of
      83) and in 84% of the ranitidine group (74 of 88). No serious adverse events were
      reported in either group. We conclude that roxatidine 150 mg once daily is as
      effective and safe for the treatment of acute duodenal ulcer as ranitidine 300 mg
      once daily.

PMID- 9001838
TI  - Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20
      mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo.
AB  - This multicenter, double-masked, randomized, parallel-group study compared the
      efficacy, tolerability, and safety of amlodipine 5 mg/benazepril 20 mg,
      amlodipine 5 mg, benazepril 20 mg, and placebo in patients with essential
      hypertension. After a placebo run-in period, 308 patients (all white) were
      randomized to treatment groups and took medication once daily for 8 weeks. Blood
      pressure was measured after 4 and 8 weeks of treatment in the 23- to 26-hour
      period after dosing. Patients wore a noninvasive blood pressure monitor for 24
      hours before randomization and before the final visit. Investigators recorded
      adverse experiences at randomization and at study weeks 4 and 8, and obtained
      specimens for laboratory testing at randomization and at study week 8. Three
      hundred seven patients were evaluated for efficacy, and 308 for tolerability and
      safety. At end point (the last postrandomization measurement for each patient),
      the reduction in mean sitting diastolic blood pressure with the amlodipine 5
      mg/benazepril 20 mg treatment was statistically significantly greater than with
      any comparative therapy. The results of 24-hour monitoring showed that the
      amlodipine/benazepril treatment, unlike monotherapy, maintained the hourly mean
      diastolic blood pressure at < or = 90 mm Hg. A responder rate of 87.0% was
      observed with amlodipine 5 mg/benazepril 20 mg versus 67.5%, 53.3%, and 15.8%
      with amlodipine, benazepril, and placebo, respectively. This difference between
      the amlodipine/benazepril treatment group and each comparative single-agent
      treatment group was statistically significant. Drug-related adverse events
      occurred in 15.6% of patients in the amlodipine/benazepril group and in 24.7%,
      6.5%, and 11.7% of patients in the amlodipine, benazepril, and placebo groups,
      respectively. Edema occurred less often in the amlodipine/benazepril group than
      in the amlodipine group. Overall, once-daily therapy with amlodipine 5
      mg/benazepril 20 mg provided an antihypertensive effect that was statistically
      and clinically superior to amlodipine 5 mg alone, benazepril 20 mg alone, and
      placebo, was well tolerated, and was associated with less edema than the
      amlodipine treatment.

PMID- 9001839
TI  - The economics of benign prostatic hyperplasia treatment: a literature review.
AB  - Benign prostatic hyperplasia (BPH) is one of the most common benign neoplasms in
      elderly men in the United States; it has been estimated that the annual costs of
      caring for these men exceed $4 billion. This condition is rarely life
      threatening, but often affects the individual's quality of life in varying
      degrees. There are several treatments for this condition, including surgery, with
      the most common procedure being transurethral resection of the prostate. Other
      treatment options include medication (such as finasteride and terazosin), balloon
      dilation, and watchful waiting. The cost associated with BPH depends on the
      severity of the disease and the appropriate course of treatment. The objective of
      this paper is to identify and evaluate the economic research papers that have
      considered either the economic burden or costs associated with alternative BPH
      therapy options and to identify key areas for future economic research. This
      review indicates that the economic studies of BPH are diverse in nature and
      greater attention needs to be placed on the societal appraisal of competing BPH
      therapies. Other research areas include the economic analysis of both short- and
      long-run BPH treatment options, increased cost-utility analysis, and the use of
      retrospective claims database analysis using regression techniques.

PMID- 9001840
TI  - Pharmaceutical products declared by US residents on returning to the United
      States from Mexico.
AB  - The overall objective of this research project was to measure the types and
      amounts of Mexican drug products being purchased and declared to US Customs by US
      residents crossing the border in Laredo, Texas. Data for this study were obtained
      from the US Customs Declaration Form, which each person completes as he or she
      reenters the United States. Data included demographic information as well as the
      types and quantities of medications purchased. Data were collected from a
      randomly selected sample of 84 days between July 1994 and June 1995. A total of
      5624 declaration forms were analyzed. The average age of people who declared
      medications was 34.5 years. Only 9.3% of the people were 50 years of age or
      older. Fourteen of the top 15 drug products declared are classified in the United
      States as "controlled" substances. In examining the quantities of medications
      being declared, on average 11,057 diazepam tablets were declared each day, which
      is equivalent to 4,035,842 diazepam tablets per year. On average 4033 tablets of
      flunitrazepam were declared each day, which is equivalent to 1,472,045 tablets a
      year declared at one US port of entry. On average, there were 2.48 drug products
      listed on each declaration form. The majority of the drug products were
      controlled substances and, based on the types and quantities of products being
      declared, many questions can be raised with regard to US policies on the control
      and safety of Mexican drugs coming into the United States.

PMID- 9001841
TI  - Risk factors for antihypertensive medication refill failure by patients under
      Medicaid managed care.
AB  - Antihypertensive medication noncompliance is common and leads to substantial
      morbidity for patients and increased health care costs for managed-care
      organizations. A retrospective cohort study using pharmacy prescription profiles
      to estimate noncompliance was conducted to determine important risk factors for
      patient noncompliance with antihypertensive therapy for Medicaid enrollees
      participating in a managed-care plan. The pharmacy and claims data for 1395
      patients with uncomplicated hypertension who were enrollees of Tennessee's
      Medicaid managed-care program were analyzed to determine the frequency of the
      enrollees' failure to obtain timely antihypertensive medication refills
      (hereafter referred to as refill failure) and to identify the predictors of
      refill failure. Overall, refill failure occurred in 33% of 7413 refill
      opportunities studied, whereas refill failure occurred in 32% of the cases in
      which medication was dosed once daily and in 35% of the cases in which medication
      was dosed more than once daily. For patients taking alpha-blockers, there was a
      significantly lower rate of refill failure (11.0%) than for patients taking
      angiotensin-converting enzyme inhibitors, direct vasodilators, and thiazide
      diuretics. Patients taking calcium channel blockers, had a significantly lower
      rate of refill failure (38.5%) than for patients taking thiazide diuretics
      (45.5%). Younger age, medication class, multiple-daily dosing regimen, and fewer
      provider visits were all found to be significant independent predictors of refill
      failure, whereas gender and regimen complexity were not significant predictors in
      this population. Health care systems planning pharmacy-based interventions to
      improve patient compliance with antihypertensive medication for patients in a
      Medicaid managed-care program can expect to encounter high levels of refill
      failure and may want to target enrollee subgroups by age, medication class, or
      dosing regimen for intensive intervention efforts.

PMID- 9001842
TI  - Sumatriptan and lost productivity time: a time series analysis of diary data.
AB  - Two previously conducted clinical studies assessed lost nonworkplace activity
      time and lost workplace productivity time due to migraine symptoms in subjects
      using sumatriptan for 6 months to treat their migraines after a 12- to 18-week
      period of using their usual therapy without sumatriptan. Although statistically
      significant differences in lost nonworkplace activity time and lost workplace
      productivity time between the usual therapy and sumatriptan treatment periods
      were detected using the Wilcoxon signed-rank test, this test could not determine
      whether differences were attributable to inherent trends in the data. This
      current study employed time series analysis, which detects and controls for
      preexisting trends in data, to further explore the possibility that the observed
      reductions in lost time in the two clinical studies were related to management of
      the subjects with sumatriptan. The intercepts and slopes of the computed linear
      models suggest that the initiation of sumatriptan therapy produced savings of 0.8
      hours of nonworkplace activity time and 0.5 hours of workplace productivity time
      per patient per week. These savings were sustained throughout the sumatriptan
      treatment period. Preexisting trends in the data were not detected in the models.
      Thus the productivity gains are not associated with either time effects or the
      statistical phenomenon of regression to the mean, but variables that are extreme
      in initial measurements will tend to be closer to the center of the distribution
      in subsequent measurements. This strengthens the hypothesis that management of
      migraine with sumatriptan is associated with reductions in lost productivity
      time.

PMID- 9001843
TI  - Quality-of-life measures in the evaluation of antihypertensive drug therapy:
      reliability, validity, and quality-of-life domains.
AB  - Health care policy decision makers and clinicians have come to realize that drug
      therapy should offer more than just efficacy and safety, which are determined in
      controlled clinical trials. During the last decade, quality of life (QOL) has
      become one of the most important variables in selecting which drug therapy should
      be used in a particular patient population. This is especially the case with
      antihypertensive drug therapy in which clinicians and patients have to make trade
      offs between the increased health risk of hypertension and the common side
      effects of antihypertensive therapy. Maintenance therapy is the key to successful
      control of high blood pressure; however, the side effects of drug therapy may
      lead to a decrease in patient compliance, a decrease in treatment success, and a
      reduction in a patient's QOL. In the assessment of QOL, the use of reliable and
      valid instruments to measure the appropriate domains is crucial. We reviewed 76
      clinical trials involving antihypertensive drugs in which the QOL of patients as
      one of the outcome measures was evaluated. The problem of inadequate information
      on the psychometric properties of the instruments used to measure QOL was found
      to be most serious when the instruments were created specifically for individual
      studies. Of the clinical trials involving the use of these self-created
      instruments, only 4% provided any kind of reliability, and only 13% provided any
      kind of validity information. The most commonly measured QOL domains in these
      clinical trials were symptomatic well-being/side-effect profile, psychological
      well-being, sleep, sexual function, and positive well-being and social
      participation. The reliability and validity data were generally available for the
      instruments measuring psychological well-being. More work is needed to establish
      the validity of the instruments measuring positive well-being and social
      participation, sleep, and sexual function. Clinical studies on the QOL of
      patients receiving antihypertensive therapy should use instruments with
      established reliability and validity data, which measure the QOL domains relevant
      to the patient and to the intervention being evaluated.

PMID- 9001844
TI  - Practical issues in conducting pharmacoeconomic studies.
AB  - Many difficulties are inherent to pharmacoeconomic studies. Because these studies
      are observational, there are many factors that cannot be controlled; for example,
      there are many variations across the country in the practice of any particular
      therapy. Therefore, designing a case report form that will match the source
      documents from various investigator sites is not easy. Issues arise in every
      activity such as choice of investigator site, data collection, data analysis, and
      interpretation of the results. These issues will be discussed, and an example of
      a pharmacoeconomic study conducted to evaluate the cost-effectiveness of patch
      testing in patients diagnosed with allergic contact dermatitis will be presented.

PMID- 9001845
TI  - Impact of fears on quality of life in patients with a silent disease:
      osteoporosis.
AB  - Fears and apprehensions are often cited as contributing to decreased quality of
      life; however, questions relating to worry over the future are rarely included in
      generic quality-of-life questionnaires. We report an effort to quantify the
      effect of fear on quality-of-life domains as measured by using the Short-Form 36
      (SF-36) Health Survey. In the course of developing an osteoporosis-targeted
      quality-of-life (OPTQoL) questionnaire, we asked participants to complete the SF
      36 Health Survey and another questionnaire containing items that women with
      osteoporosis could be expected to find difficult or worrisome. Two hundred twenty
      two women with established osteoporosis (loss of height, kyphosis, history of
      fractures); 101 women with known low bone mineral density (BMD) but without
      established osteoporosis; and 142 women with no known osteoporosis completed both
      the osteoporosis questionnaire and the SF-36 Health Survey. This test version of
      the OPTQoL contained two domains for fears of osteoporosis and the consequent
      fractures and deformities; these domains were termed fears now and fears future.
      After adjusting for age and selected comorbidities, we estimated the additional
      contribution of the two fears domains on the domain scores of the SF-36 Health
      Survey. For women with established osteoporosis, the fears now domain explained
      4% to 8% of the variance within each domain of the survey. For women with low BMD
      only, fears now had a significant effect only on the physical functioning domain
      of the survey and explained 4% of the variance of that domain. Fears future had a
      significant role in explaining the SF-36 Health Survey score on all domains
      except physical functioning among women with established osteoporosis; however,
      the fears future domain explained less of the variance (2% to 5%) among these
      women than did the fears now domain. For women with low BMD only, fears future
      had a significant impact only on the mental health and the general health domains
      (4% and 5% of the variance, respectively). Osteoporosis-related fears appear to
      explain a small but significant percentage of the variation in quality of life
      for women in midlife.

PMID- 9001846
TI  - Disease management--separating fact from fantasy.

PMID- 9001848
TI  - Monitoring and evaluating disease management: information requirements.
AB  - This paper addresses information essential to the creation, monitoring, and
      evaluation of disease management programs within managed-care organizations.
      Sound procedures for the collection and analysis of data are vital components of
      any effective disease management program. This presentation argues for a
      systemwide, rather than an atomistic, approach to data collection and analysis.
      Because every health system serves different populations, reliable demographic
      and health resource use data must be collected. Similarly, baseline data on
      physician prescribing behavior, patient compliance, and treatment costs are
      necessary to identify areas in need of improvement. Particular care must be taken
      to ensure that valid statistical models are developed to reflect the realities of
      the health system. The strengths and weaknesses of various internal and external
      data sources are discussed, with an emphasis on correlating and integrating
      information to provide comprehensive analyses of treatments and outcomes. The
      effects of different financial arrangements on data issues are also discussed,
      particularly in terms of contracting issues at successive stages in the
      development of a disease management program. This paper examines, in detail, data
      issues relating to monitoring prescribing behavior, modeling therapy
      interventions, classifying outcomes, and utilization of resources and treatments.
      Finally, this presentation makes specific recommendations for designing valid
      procedures for data collection and analysis.

PMID- 9001847
TI  - Disease management: definitions and exploration of issues.
AB  - Disease management (DM) appears to be sweeping the health care industry. Its
      supporters claim that it can produce optimal health care outcomes through
      enhancements in the quality of care provided to patients and effective control of
      costs. This paper examines the primary reasons for the recent popularity of DM,
      discusses several thematic components common to various definitions of DM, and
      compares the often overly optimistic claims made for DM with the realities of how
      such programs are actually implemented. Finally, it examines critical issues and
      controversies that participants in DM must consider as this approach to managing
      patient care evolves.

PMID- 9001849
TI  - Assessing the input costs of disease management programs.
AB  - This paper presents a practical blueprint for modeling and evaluating the costs
      of disease interventions. Retrospective estimates of therapy costs and analyses
      of various treatment pathways are critical to projecting the likely cost impacts
      of disease management programs. This presentation outlines the information
      requirements necessary to identify baseline costs, to set cost outcomes targets,
      and to monitor costs over the life of an agreement. The chief components of this
      process are: (1) developing a framework for input cost analysis; (2) identifying
      costing requirements for various types of disease management interventions; (3)
      identifying key classifications in such a cost framework; and (4) identifying
      principal obstacles to cost assessment.

PMID- 9001850
TI  - Measuring and monitoring outcomes of disease management programs.
AB  - After a brief analysis of the financial and health care motives that have led to
      the current boom in disease management (DM) programs, this paper discusses the
      pragmatic realities of a particular DM program for treating asthma. A model of
      the institutional structures necessary for DM to work is presented, emphasizing a
      process of continuous quality improvement in technical, clinical, and managerial
      processes. Significant differences between the conventions of controlled clinical
      trials and the realities of actual patient care may lead to unrealistic
      expectations about DM, making sound managerial practices and effective
      communication even more important. A "data warehouse" can help health care
      systems master the intricacies of programwide data collection and analysis,
      making possible sound decisions regarding treatment regimens and changes in
      physician and patient behavior. This paper concludes with a discussion of how the
      Prudential Health Care DM program for asthma makes use of the practices and
      systems discussed above.

PMID- 9001851
TI  - Disease management contracting: key elements.
AB  - Although the data at the outset of a contractual agreement can often be
      incomplete or inaccurate, and the analytical tools necessary to interpret these
      data are still being developed, partners about to enter a disease management (DM)
      arrangement can nonetheless take steps to ensure that the relationship will be
      sound and successful. Pharmaceutical firms (and other service providers) wishing
      to enter into DM relationships with managed-care organizations must consider
      several important factors of the contracting process to protect their financial
      interests and benefit from the partnership, particularly in the first 1 to 2
      years of the arrangement. This paper provides recommendations for both general
      strategies and financial elements of DM contracting, and defines several
      contractual elements that can help to secure a harmonious and profitable
      partnership. These suggestions address concerns for various types of
      partnerships, including risk-sharing and fee-for-service plans. Early and careful
      consideration of the legal aspects of the DM business can protect companies from
      incurring significant, unanticipated losses.

PMID- 9001852
TI  - Disease management contracting: legal issues.
AB  - The legal issues surrounding disease management (DM) agreements can be complex
      and confusing to participants whose primary expertise is in the management or
      providing of health care. Because DM is such a rapidly evolving field, attorneys
      can provide invaluable guidance in avoiding legal pitfalls that can arise from
      the partners' sometimes-differing goals and expectations. Although managed-care
      organizations (MCOs) are generally already familiar with the legal issues in DM,
      the independent partners in DM agreements, often drug companies, may be less
      familiar with the various state and federal licensing and regulatory requirements
      that may apply to their DM activities. For this reason, it is important that,
      unless they are prepared to take on the responsibilities involved with licensing
      and regulation, independent partners of MCOs should contractually state that they
      are not "health care providers" and should not engage in activities that would
      make them subject to regulation. In addition, partnership contracts must be
      carefully defined to avoid running afoul of federal and state anti-kickback laws,
      which prohibit certain impermissible inducements to purchase health care products
      or services covered by Medicare/Medicaid.

PMID- 9001853
TI  - A disease management case study in infectious disease.
AB  - One of the earliest attempts at risk sharing between a managed-care organization
      and a pharmaceutical company is the infectious disease management program
      developed since late 1993 by Intergroup of Arizona and Eli Lilly and Company
      (Indianapolis, Indiana) in conjunction with the Center for Pharmaceutical
      Economics at The University of Arizona (Tucson, Arizona) and other entities. In
      the first phase of the program, protocols were built around eight infectious
      disease states, and it was recognized that second-line antibiotics were often
      prescribed when more economical first-line antibiotics would be equally
      effective. The second phase of the program emphasized developing treatment
      algorithms focused on patient outcomes, using merged medical and pharmacy claims
      databases to determine the effects of the antibiotic changes. To implement the
      program successfully, some significant shifts in corporate, medical, and patient
      mind-sets had to be addressed. A primary goal was to encourage a movement from a
      rebate, volume-driven, cost structure to a shared-risk, appropriate-use,
      reimbursement method in which both managed-care and the pharmaceutical company
      incentives could mesh as far as possible. Over the long term, it is hoped that
      this project will lay the groundwork for other disease management programs for
      high-impact, frequently occurring diseases.

PMID- 9001854
TI  - A disease management case study on asthma.
AB  - This paper provides an overview of how one pharmacy benefits manager, MedImpact
      Pharmaceutical Management, Inc. (San Diego, California), approaches its disease
      management (DM) program for asthma. This group's experience with DM counters the
      common but fallacious belief that reduction of component costs leads to reduction
      of total expenditures. In fact, greater expenditures on certain components (in
      particular, drug therapies and preventive and follow-up visits to physicians) can
      result in greatly reduced overall expenditures by reducing hospitalizations and
      emergency department treatments for asthmatic patients. The program addresses
      four essential components of DM: physician intervention, patient empowerment,
      health risk management, and pharmaceutical care. For each of these areas, careful
      statistical analysis, effective education, and integrated management can help
      improve patient care while reducing overall costs.

PMID- 9001855
TI  - What is new in cutaneous laser research.
AB  - Laser surgery is a dynamic, growing field in dermatology. Recent advances in
      cutaneous laser applications include the treatment of scars, wrinkles, warts, and
      stretch marks. Current investigation focuses on permanent hair removal and leg
      vein treatment as well as improvement of current treatment of vascular and
      pigmented lesions. This article provides an overview of laser applications and
      focuses on novel research.

PMID- 9001856
TI  - Advances in dermatologic surgery.
AB  - The major advances in dermatologic surgery for this period reside in the areas of
      diagnosis and management of cutaneous melanoma, laser surgery, tumescent
      liposuction, and tumorigenesis. A closer look at these advances is presented.

PMID- 9001857
TI  - Advances in chemical peeling.
AB  - Chemical peeling is traditionally discussed in terms of the depth of injury:
      superficial, medium, or deep. There have been a number of important advances in
      both superficial and medium-depth chemical peeling over the last several years.
      This article reviews the state of the art of these techniques and the increasing
      understanding of their effects on skin.

PMID- 9001859
TI  - Clinical updates in hair.
AB  - It is now known that there are major differences in the systemic and cellular
      mechanisms that mediate hair loss in women versus men. The severity or degree of
      hair loss in women with androgenetic alopecia is usually much less than in men.
      It is usually assumed that the hormonal basis for androgenetic alopecia in women
      is the same as in men; that is, the same target tissue-active androgens,
      testosterone and dihydrotestosterone, are being produced systemically to
      aggravate scalp hair follicles, resulting in hair loss. This article reviews some
      of the latest findings in androgenetic alopecia for both men and women, along
      with new and old treatments and drugs, doses, and effectiveness. Research
      findings indicate that levels of androgen-metabolizing enzymes and receptors
      differ in the scalps of women versus men, which may be important in formulating
      more effective hair growth treatments in the future.

PMID- 9001860
TI  - What is new in clinical research in wound healing.
AB  - Treating the underlying pathophysiology of the wound remains of utmost
      importance. Several new treatment modalities may soon be available as adjunctive
      treatments. The efficacy of some remains to be established in well-controlled
      clinical studies.

PMID- 9001858
TI  - Cutaneous gene therapy.
AB  - Gene therapy efforts in a variety of tissues have foundered on fundamental
      technologic barriers, such as difficulties in achieving high-efficiency gene
      transfer to diseased tissues and in sustaining delivered transgene production.
      The skin offers an attractive tissue for development of approaches to therapeutic
      gene delivery by virtue of its accessibility for regulation by topical agents,
      the ease of gene transfer into cutaneous tissues, and the ready ability to
      monitor the impact of somatic gene transfer. With the ability of the skin to
      deliver therapeutic polypeptides to the systemic circulation and the recent
      molecular characterization of monogenic skin diseases, efforts to target genes to
      the skin are expected to accelerate. The current status of gene therapy efforts
      is reviewed, with a special focus on the skin.

PMID- 9001861
TI  - Recent advances in the treatment of psoriasis.
AB  - We have seen great progress in the past decade in our understanding of the
      pathogenesis of psoriasis. The fruits of this knowledge are being realized in
      many of the exciting immunologic therapies currently in development. The
      potential for astute clinical observation to produce effective therapies and to
      change the direction of research has been proven in the past and still remains as
      an avenue for the future. Although individual treatments were discussed in this
      article, combination therapy is likely to continue to play a major role.
      Additionally, because future therapeutic developments are not likely to be free
      of toxicity, rotational therapy may still be necessary. Many questions remain
      unanswered. Substantial progress is just beginning into the.

PMID- 9001863
TI  - Dermoscopy (epiluminescence microscopy) of pigmented skin lesions. Current status
      and evolving trends.
AB  - Dermoscopy (epiluminescence microscopy) is a noninvasive technique that is
      designed for in vivo microscopic examination of pigmented skin lesions,
      particularly for the early recognition of malignant melanoma. Since its
      introduction, dermoscopy technique has undergone extensive improvements; the
      instruments have become more readily available; and the diagnostic indications,
      benefits, and limitations have been better delineated. This article offers a
      concise review of the technique of dermoscopy, assesses the current status, and
      makes some predictions for future applications.

PMID- 9001862
TI  - Recent investigations on vitiligo vulgaris.
AB  - Vitiligo is a depigmenting disorder of the skin caused by destruction of
      melanocytes. The depigmented skin has several abnormal functions, including some
      autonomic nervous functions. The inflammatory response in the depigmented skin is
      muted. Recent genetic and epidemiologic studies indicate that vitiligo affects
      men and women equally. The prevalence in the population is about one in 200.
      Vitiligo seems to be transmitted as a polygenic trait. New data suggest that it
      is not associated with autoimmune endocrine disorders, but more comprehensive
      studies are required.

PMID- 9001864
TI  - Acne. An overview of clinical research findings.
AB  - Although acne represents the most common chronic skin condition seen by
      dermatologists, there are still many unanswered questions regarding its
      pathophysiology, and patients are still in need of more effective therapies,
      particularly those aimed at the hormonal aspects of acne. Recent clinical
      research has led to advances in our understanding of factors such as cytokines in
      follicular hyperkeratinization and the role of androgens in acne, the emergence
      and significance of antibiotic resistance of P. acnes, the long-term safety and
      efficacy of isotretinoin, and the safety and efficacy of new topical retinoids,
      such as tazarotene and adapalene. Fruitful interactions between basic scientists
      and clinical researchers within medicine and the pharmaceutical industry will, it
      is hoped, provide for future advances in this area.

PMID- 9001865
TI  - Pediatric dermatology.
AB  - The latest studies regarding the controversial and concerning subjects of
      pigmented nevi and melanoma in children are reviewed. Additional topics covered
      include dermatologic conditions that feature genetic mosaicism, theories of
      pathogenesis of Langerhans cell histiocytosis, new clinical information regarding
      juvenile xanthogranulomas, and the unique features of pyoderma gangrenosum in
      infants and children.

PMID- 9001866
TI  - Current management of onychomycosis. An overview.
AB  - Until recently pedal onychomycosis, particularly when it affected several nails
      or involved a large nail plate area, was often regarded as untreatable. The
      advent of new therapies such as itraconazole, terbinafine, and fluconazole has
      been a significant and welcome addition to the armamentarium of therapies at the
      disposal of the physician. These drugs appear in the nail plate within days of
      starting oral therapy, being taken up by both the nail matrix and the nail bed.
      The duration required for effective therapy has been reduced, while the efficacy
      rates and cost-effectiveness have increased compared with the older treatments,
      such as griseofulvin. Some of the newer agents appear to have a wider spectrum of
      activity. Thus far, the newer agent have exhibited a low risk to benefit ratio. I
      may be possible to combine oral therapies with topical and surgical treatments,
      thereby further increasing efficacy rates and the cost-effectiveness while
      decreasing adverse effects and duration of oral therapy.

PMID- 9001867
TI  - What is new in clinical research in contact dermatitis.
AB  - The field of cutaneous allergy has enjoyed dynamic research advances in
      epidemiology and clinical contact dermatitis. Studies regarding outcomes
      analysis, validity, predictive value, and sensitivity have allowed clinicians to
      better understand the importance of patch test results. In the clinical arena,
      new and clinically relevant allergens are being discovered, such as
      corticosteroids, metals, preservatives, surfactants, and glues. Continued
      epidemiologic surveillance of new allergens will enable manufacturers to develop
      safer products for patients to use.

PMID- 9001869
TI  - Dermatopathologic advances in clinical research. The expression of antibody to
      CD34 in mucocutaneous lesions. off.
AB  - The human progenitor cell antigen, CD34, is selectively expressed in most
      hematopoietic colony-forming cells from normal human bone marrow, and in a
      significant proportion of acute leukemias. Within the dermis, CD34 is normally
      expressed by endothelial cells, dendritic cells, and the spindle-shaped cells
      around adnexal structures. Benign and malignant vascular lesions, adnexal tumors
      differentiating toward the external root sheath (trichilemmomas and pilar
      tumors), specific benign soft tissue tumors (spindle cell lipoma and solitary
      fibrous tumors), and many of the gastrointestinal stromal tumors uniformly
      express CD34 antigen. CD34 expression is also often present in benign tumors of
      neural origin; however, it is less consistently present in malignant peripheral
      nerve sheath tumors.

PMID- 9001868
TI  - The dynamic interplay of malignant and benign T cells in cutaneous T-cell
      lymphoma.
AB  - Cutaneous T-cell lymphoma is a malignancy of functional, tissue-specific T cells.
      Many characteristics of the disease can be explained by virtue of the ability of
      the malignant cell population to actively participate in the host's immunologic
      network. Various aspects of this dynamic interplay between malignant and benign T
      cells are discussed, including impact on diagnosis, staging, and therapy.

PMID- 9001870
TI  - Advances in Kaposi's sarcoma.
AB  - KS remains a challenge to clinicians and investigators more than a century after
      its initial description. Debate continues as to the cell of origin, as well as
      whether or not it is a true cancer. KS appears to be an opportunistic neoplasm,
      which in its earliest phase retains some features of a benign hyperproliferative
      process, but in its late stages behaves like an aggressive malignancy.
      Pathogenesis seems to involve a predisposed individual (genetically susceptible
      or immunologically compromised) who comes into contact with an infectious agent,
      most likely a virus. Cytokines appear to play a major role in the growth of the
      tumor. The exact role of the KSHV in this process will likely be the subject of
      much investigation in the future.

PMID- 9001871
TI  - What is new in clinical research of viral diseases of the skin.
AB  - Viral diseases of the skin have become a much more serious problem with the
      increasing number of patients immunosuppressed by either AIDS or cancer
      chemotherapy. The emphasis in research on the diagnosis and treatment of these
      diseases is similar to that on the bacterial diseases several decades ago.

PMID- 9001872
TI  - Dermatologic drug use during pregnancy and lactation.
AB  - Physicians are often asked to prescribe medication for women during the
      childbearing years. This article reviews which dermatologic drugs have been
      reported to interfere with contraceptive efficacy, which should be avoided, and
      which have the fewest contraindications for use during pregnancy and lactation.
      Corticosteroids and tretinoin are discussed in detail. Sources and guidelines for
      choices of dermatologic drugs for women of childbearing age are presented.

PMID- 9001873
TI  - Evaluation of the quality of life of patients with insulin-dependent diabetes
      mellitus before and after organ transplantation with the SF 36 health survey.
AB  - OBJECTIVE: To find out if patients with insulin-dependent diabetes mellitus who
      had undergone successful pancreas and kidney transplantation thought that their
      quality of life was better than that of patients before transplantation or
      patients who had rejected the grafts. DESIGN: Cross-sectional study. SETTING:
      Teaching hospital, Germany. SUBJECTS: 110 of 143 patients to whom questionnaires
      had been sent. Patients were divided into those awaiting transplantation who did
      not require dialysis (n = 9), those awaiting transplantation who were receiving
      dialysis (n = 27), those with functioning grafts after transplantation (n = 34),
      those with functioning kidneys taking insulin (n = 34); and those who had
      rejected both grafts and were being treated with both dialysis and insulin (n =
      6). INTERVENTIONS: Short Form (SF) 36 health survey and two visual analogue
      scales. MAIN OUTCOME MEASURES: Comparison of quality of life scores. RESULTS: The
      duration of dialysis before transplantation was the only feature that differed
      significantly between the responders (median 24 (range 0-133) months) compared
      with the non-responders (16 (0-70) months), p < 0.01. The psychometric quality of
      the SF 36 yielded good variance and reliability in the subscales, and excellent
      "scale fit" values (between 90% and 100%). Patients who had undergone successful
      transplantation scored significantly higher than those who had rejected their
      pancreatic graft in the subscales "vitality" (mean (SD) transformed score 64.4
      (15.2) compared with 55.5 (18.9), p < 0.05), and "general health perception"
      (60.8(18.2) compared with 50.2 (22.5), p < 0.05). The worst ratings of quality of
      life were given by patients awaiting transplantation (whether or not they were
      being dialysed) and those who had rejected both grafts. CONCLUSIONS: The SF 36
      health survey is a valid instrument for testing patients' perceptions of outcome
      after transplantation. Those patients who had undergone successful pancreas and
      kidney transplantation gave the highest scores.

PMID- 9001874
TI  - Efficacy of double gloving with a coloured inner pair for immediate detection of
      operative glove perforations.
AB  - OBJECTIVE: To compare the efficacy of double gloving with an inner coloured pair
      of gloves and double gloving with classic gloves, for prompt detection of
      perforation during a single standard operation. DESIGN: Prospective, randomised
      study. SETTING: Teaching hospital, France. SUBJECTS: 100 Consecutive patients
      with haematological malignancy or AIDS, who were referred for implantation of a
      vascular access port. INTERVENTIONS: Insertion of a central line with an
      implantable chamber under local anaesthesia. The use of double gloving with an
      inner coloured pair or with classic gloves was decided preoperatively by random
      allocation. MAIN OUTCOME MEASURES: Visual detection of one or more perforations
      on one or more gloves during operation, localisation of the perforation(s), and
      post-operative evaluation of the water tightness of the gloves. RESULTS: There
      were a total of 14 perforations of the outer gloves, 9 were detected during
      operation in the coloured inner pair group compared with none in the standard
      gloves group. Postoperative testing showed that there were no undetected
      perforations in the coloured inner pair group compared with 5 in the standard
      gloves group. CONCLUSIONS: Double gloving with a coloured inner pair is effective
      in the peroperative detection of accidental perforations in surgical gloves.

PMID- 9001875
TI  - Antibiotic prophylaxis in umbilical and incisional hernia repair: a prospective
      randomised study.
AB  - OBJECTIVE: To find out if preoperative prophylaxis would reduce infection rates
      after umbilical and incisional hernia repair. DESIGN: Randomised controlled
      trial. SETTING: Teaching hospital, Israel. SUBJECTS: 35 Patients who presented
      with umbilical (n = 19) or incisional (n = 16) hernias during a period of 8
      months. INTERVENTIONS: Cefonicid 1 g was given by intravenous infusion to
      alternate patients 30 minutes before the operation. MAIN OUTCOME MEASURES: Wound
      infection. RESULTS: The groups were comparable for age, body mass index, grade of
      surgeon, operating time, and size of hernial ring. The wound infection rates were
      0/8 compared with 4/8 for incisional hernia repairs (p = 0.08) and 1/9 compared
      with 4/10 for umbilical hernia repairs (p = 0.3). The overall rate was 1/17
      compared with 8/18 (p = 0.02). CONCLUSIONS: Single dose antibiotic puphylaxis
      seems to exert a beneficial effect on the wound infection rate after umbilical
      and incisional hernia repair.

PMID- 9001876
TI  - Early operation for severe corrosive injury of the upper gastrointestinal tract.
AB  - OBJECTIVE: To describe our experience of treating severe corrosive burns of the
      upper gastrointestinal (GI) tract. DESIGN: Open study. SETTING: Teaching
      hospital, France. SUBJECTS: 18 patients who had swallowed an alkaline substance
      (caustic soda in 10 cases) and 4 who had swallowed either hydrochloric or
      sulphuric acid. INTERVENTIONS: Endoscopy was done a mean of 4 hours after the
      substance had been swallowed. 10 patients underwent oesophagogastrectomy without
      thoracotomy. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: 4 of the 10
      patients died and 3 developed postoperative complications. Of the 12 patients
      treated by feeding jejunostomy 7 developed stenosis that required operation and 3
      developed stenosis that responded to dilatation. None of the 12 died.
      CONCLUSIONS: Early oesophagoscopy allowed optimal management. Patients died if
      they swallowed more than 60 ml of a strong alkaline substance. When patients are
      treated conservatively about half will develop stenoses that require operation.

PMID- 9001877
TI  - Endoscopic treatment of oesophagoairway fistula with oesophageal balloon
      prosthesis.
AB  - OBJECTIVE: To describe our experience with a cuffed oesophageal prosthesis in the
      management of malignant oesophagoairway fistulas. DESIGN: Retrospective study.
      SETTING: Teaching hospital, Denmark. SUBJECTS: Nine patients treated with a
      balloon cuffed oesophageal prosthesis during the period 1987-93. MAIN OUTCOME
      MEASURES: Endoscopic assessment of the fistula compared with the results and
      complications of treatment. RESULTS: The prosthesis were inserted without
      complications. Eight patients had total relief of aspiration and were able to eat
      a semisolid diet. Three patients needed reintervention. Patients with little or
      no stenosis of the tumour seemed to be at considerable risk of dislodgement of
      the tube and those with large fistulas developed protrusion of the balloon into
      the tracheal lumen. CONCLUSION: Intubation with the cuffed oesophageal prosthesis
      is safe and relatively inexpensive. Other treatments should be considered in
      patients with minor stenosis of the tumour or a large fistula.

PMID- 9001878
TI  - Transduodenal excision of tumours of the ampulla of Vater.
AB  - OBJECTIVE: To evaluate the symptoms, diagnostic procedures, and treatment by
      transduodenal excision, of tumours in the ampulla of Vater. DESIGN: Open study of
      consecutive patients. SETTING: University hospital, Denmark. SUBJECTS: Six
      patients with tumours in the ampulla of Vater. INTERVENTIONS: Ultrasonography,
      duodenoscopy, and endoscopic retrograde cholangiopancreatography (ERCP).
      Endoscopic biopsy if tumour was visible at the papilla. Transduodenal excision of
      the ampulla and anastomoses of the common duct and pancreatic duct to the
      duodenum. MAIN OUTCOME MEASURES: Postoperative complications and survival.
      RESULTS: None of the tumours could be seen on ultrasonography. All the tumours
      were diagnosed on duodenoscopy with ERCP. The histopathological diagnoses of the
      endoscopic biopsy specimens were adenoma (n = 3), suspicion of adenocarcinoma (n
      = 2), and adenocarcinoma (n = 1). Curative resection by transduodenal excision of
      the ampulla of Vater was possible in all cases. Pathological examination of the
      surgical specimens showed three adenomas and three adenocarcinomas. One patient
      had a recurrence after 2.5 years and had a further resection. Three patients died
      after one, three, and nine years, respectively; two had no recurrence and one was
      suspected of having one. The other three patients were alive 8-20 months after
      the operation. CONCLUSION: The procedure is recommended for small and probably
      benign tumours and, when technically possible, in malignant tumours in patients
      at high operative risk. Close postoperative follow-up with duodenoscopy and ERCP
      is recommended.

PMID- 9001879
TI  - Topical clobetasol propionate compared with placebo in the treatment of
      unretractable foreskin.
AB  - OBJECTIVE: To assess whether it is the steroid alone or the gentle physical
      retraction combined with ointment that is responsible for the excellent results
      observed with topical steroid treatment of unretractable foreskin. DESIGN:
      Prospective, randomised, double-blind study. SETTING: University hospital,
      Sweden. SUBJECTS: 30 Boys randomised to be treated with clobetasol propionate (n
      = 15) or placebo (n = 15). INTERVENTIONS: The boys were examined 1, 2 and 6
      months, respectively, after treatment. MAIN OUTCOME MEASURES: Comparison between
      the effects of clobetasol propionate and placebo. RESULTS: Two patients in the
      steroid group and one in the placebo group withdrew from the study. 10 Boys in
      the steroid group showed an improvement within 2 months. The remaining 3 boys had
      no effect and were circumcised. Histopathological examination showed lichen
      sclerosus et atrophicus. Seven boys in the placebo group improved. The 7 non
      responders were prescribed clobetasol propionate ointment, and all 7 improved.
      CONCLUSION: 17 of 27 boys referred with "phimosis" were successfully treated with
      an ointment and gentle traction. When clobetasol propionate was given the non
      responders success rate was increased to 24/27 (89%).

PMID- 9001881
TI  - Survival after necrotising streptococcal myositis: a matter of hours.

PMID- 9001882
TI  - Undiagnosed phaeochromocytomas in the perioperative period.

PMID- 9001883
TI  - Ruptured aneurysm of the renal artery in a woman with a solitary kidney.

PMID- 9001880
TI  - Failure of dobutamine to improve liver oxygenation during resuscitation with a
      crystalloid solution after experimental haemorrhagic shock.
AB  - OBJECTIVE: To evaluate the effects of dobutamine on peripheral and hepatic tissue
      oxygen tensions during the treatment of haemorrhagic shock. DESIGN: Randomised,
      controlled trial. SETTING: University hospital, Finland. SUBJECTS: 12 Piglets,
      weight 20 kg. INTERVENTIONS: Haemorrhagic shock (40% of blood volume removed) and
      resuscitation with crystalloid solution. Dobutamine infused (6.5
      micrograms/kg/min) during resuscitation in 6 animals and 6 served as controls.
      MAIN OUTCOME MEASURES: Haemodynamic and systemic oxygen transport variables.
      Hepatic, subcutaneous, transcutaneous, and conjunctival oxygen tensions measured
      continuously with polarographic electrodes. RESULTS: All values decreased
      significantly during bleeding. Resuscitation restored the mean arterial pressure
      in both groups, and cardiac output exceeded the baseline by 24% in the dobutamine
      group (p < 0.05 compared with control). There was no difference in oxygen
      delivery and consequently tissue oxygen tensions remained at the control level in
      the dobutamine group. CONCLUSIONS: Dobutamine infusion did not improve tissue
      oxygenation when used in addition to crystalloids to treat hypovolaemic shock.

PMID- 9001884
TI  - Pelvic giant lymph node hyperplasia (Castleman's disease): a surgical and
      radiological approach.

PMID- 9001885
TI  - The erythropoietin-producing cells.

PMID- 9001886
TI  - Role of nitric oxide in cell adhesion and locomotion.

PMID- 9001887
TI  - Zonal expression of angiotensin II-AT1-receptor genes in rat kidneys.
AB  - This study aimed to examine the relative distribution of ANGII-AT1-receptor gene
      expression in different zones of the rat kidney, namely the glomeruli, cortex
      (CO), outer and inner stripes of outer medulla (OSOM and ISOM, respectively) and
      inner medulla (IM). By RNAse protection we found a ratio for the overall
      abundance of AT1 mRNA of 1, 0.68, 0.52, 0.86 and 0.46 for glomeruli, CO, OSOM,
      ISOM and IM, respectively. The intrazonal proportion of AT1a and AT1b mRNA was
      determined by RT-PCR, which yielded values for the ratio AT1a/AT1b of 1.1, 4.7,
      4.4, 3.7 and 1.9 for glomeruli, CO, OSOM, ISOM, and IM, respectively. These
      findings suggest a zonal heterogeneity in the expression of AT1-receptor genes
      such that the highest expression is found in glomeruli and ISOM, whilst the
      papilla shows the lowest level of expression. Moreover, there appears to exist a
      corticopapillary gradient for the relative expression of AT1a and AT1b-receptor
      genes such that the preponderance of AT1a-receptor gene expression decreases into
      a papillary direction. Within the CO glomeruli appear as an isle of AT1b
      receptors of relatively high expression.

PMID- 9001888
TI  - Upregulation of epidermal growth factor and its receptor in the kidneys of rats
      with streptozotocin-induced diabetes.
AB  - We have studied the acute changes (up to 30 days) in the expression of epidermal
      growth factor (EGF) and its receptor (EGFr) in the kidneys of adult male Wistar
      rats made diabetic by a single intravenous injection of streptozotocin (55 mg/kg)
      using a combination of immunocytochemical staining and in situ hybridization
      histochemistry. In the absence of insulin treatment, diabetic rats displayed
      renal growth (hypertrophy and hyperplasia). It was accompanied by an increase in
      immunostainable EGF within the thick ascending limb (TAL) of the loops of Henle
      which was apparent within 24 h of the onset of diabetes, reached a peak by day 7
      and persisted to the end of the experimental period (day 30). In situ
      hybridization histochemistry revealed that these changes were preceded by a rapid
      rise in EGF mRNA in the cells of the TAL, which was highest after 1 day but
      declined to control levels by day 7. Increased immunostainable EGFr was evident
      in both the proximal and TAL and in the cortical collecting ducts from day 1.
      Staining of the proximal tubules declined rapidly after day 1 but that of the TAL
      and collecting ducts persisted until day 7 and declined thereafter. These results
      are discussed in light of the role of EGF in the hypertrophy and repair of the
      diabetic kidney.

PMID- 9001890
TI  - A specific Thy-1 molecular epitope expressed on rat mesangial cells.
AB  - An experimental model of proliferative glomerulonephritis induced by antibodies
      against the Thy-1 antigen has been established and used to study the pathological
      sequence from mesangiolysis to mesangial proliferation. However, the functional
      role of the Thy-1 molecule distributed on rat glomerular mesangial cells remains
      unknown, so the present study was undertaken to determine the precise subcellular
      localization of Thy-1 molecules in vitro using two anti-Thy-1 monoclonal
      antibodies, 1-22-3 and OX-7. Immunofluorescence and immunoelectron microscopic
      studies in combination with laser scanning analysis showed that the localization
      of 1-22-3 and OX-7 bound to cultured rat mesangial cells differed, particularly
      when cocultured with vascular endothelial cells. An epitope recognized by 1-22-3
      was concentrated specifically on the mesangial cell surfaces facing the
      neighboring endothelial cells. In contrast, OX-7 bound to mesangial cell surfaces
      and extracellular parts in a diffuse pattern independent of contact with
      endothelial cells. This finding is consistent with our previous ultrastructural
      study in which the reactivity of 1-22-3 with normal kidney tissue was limited to
      mesangial cell surfaces facing endothelial cells. These results led us to
      conclude that the specific Thy-1 molecular epitope recognized by 1-22-3 is
      associated with points anchoring mesangial and endothelial cells, where this anti
      Thy-1 antibody binds after injection in vivo, resulting in mesangial cell
      detachment from the vascular capillary wall, mesangiolysis and mesangial cell
      dysfunction. We believe that the critical epitope detected by 1-22-3 in this
      study plays an important role in mesangial cell function and injury.

PMID- 9001889
TI  - Mechanism of induction of prostaglandin E2 production by endothelin 1 in cultured
      rat mesangial cells.
AB  - The phospholipase A2 inhibitors mepacrine, ONO-RS-082, and AACOCF3 completely
      inhibited prostaglandin E2 production induced by endothelin 1 in cultured rat
      mesangial cells, suggesting that phospholipase A2 is a critical enzyme in this
      process. TMB-8, an inhibitor of calcium mobilization from intracellular stores,
      abolished its production, while neither nicardipine nor chelation of
      extracellular calcium by EGTA did. The protein kinase C inhibitors, H-7 and
      staurosporine, and downregulation of protein kinase C could not inhibit
      prostaglandin E2 production, while W-7, a calmodulin inhibitor, abolished it.
      Pertussis toxin never influenced its production. Thus, endothelin 1 evokes
      prostaglandin E2 production in mesangial cells mainly through the activation of
      phospholipase A2, dependent on intracellular calcium and calmodulin and
      independent of extracellular calcium, protein kinase C, and pertussis toxin
      sensitive guanosine 5'-triphosphate binding proteins.

PMID- 9001891
TI  - The intrarenal renin-angiotensin system: a paracrine system for the local control
      of renal function separate from the systemic axis.
AB  - The kidney serves an integral role in the systemic renin-angiotensin system (RAS)
      both as an effector and as a target organ. Increasing evidence also accumulates
      that local intrarenal RAS serve as important regulators of renal function.
      Evidence is reviewed concerning the expression and potential role of components
      of the RAS in glomeruli, proximal tubule and renal interstitium. In addition to
      regulating normal renal function, local renal RAS may be triggered in response to
      renal injury and may contribute to structural and functional abnormalities,
      including increased glomerulosclerosis and tubulointerstitial fibrosis.

PMID- 9001892
TI  - From converting enzyme inhibition to angiotensin II receptor blockade: new
      insight on angiotensin II receptor subtypes in the kidney.
AB  - Since the discovery of renin, almost 100 years ago, all the components of the
      renin-angiotensin system have been characterized on a molecular level.
      Angiotensin II (Ang II) receptors can be grouped in two classes: AT1 and AT2
      receptors. In addition to these receptor subtypes, several other Ang-II-binding
      sites with different properties have been identified. The majority of Ang II
      receptors in the kidney comprises the AT1 type, whereas AT2 receptors are only
      expressed by distinct structures such as the renal capsule and the
      juxtaglomerular apparatus. The vast majority of physiological functions of
      angiotensin II in the kidney are mediated through AT1 receptors. Important
      exceptions may be the pressure-induced natriuresis and chemotaxis for
      macrophages/ monocytes, as well as growth-suppressive effects which may be
      mediated by AT2 receptors.

PMID- 9001893
TI  - The renin-angiotensin system and renal function in transgenic (mRen2)27 rats.
AB  - The transgenic rat (TGR)(mRen2)27 was the first hypertensive transgenic rat model
      developed. The model is unique in that it allows studying the effects of a single
      gene, namely the mouse salivary gland renin gene (mRen2), in the rat. The
      transgene is expressed in various rat tissues, including the central nervous
      system, adrenal gland, and the kidney. TGR exhibit a rightward shifted pressure
      natriuresis curve that is overwhelmingly angiotensin II (Ang II) dependent. The
      mRen2 transgene, the rat's own renin gene, angiotensinogen, and the type 1 Ang II
      receptor, AT1, are all expressed in the kidneys of TGR. The rat's own renin gene
      is regulated normally in renal tissue, while the mRen2 transgene operates
      independently of blood pressure. These results, coupled with findings that the
      mRen2 transgene product converts rat angiotensinogen more effectively than
      endogenous rat renin, that the TGR may have high circulating mouse renin levels
      which increase with age, and the fact that high circulating prorenin
      concentrations are present in these TGR, shed light on the kidney's role in the
      blood-pressure-elevating mechanisms of TGR. The viewpoint that the kidneys are
      not mechanistically important in this TGR model must be revised.

PMID- 9001894
TI  - Impact of renin-angiotensin system blockade on structure and function of
      glomerular membrane components in animal models of kidney disease.
AB  - The most promising therapeutic intervention to slow the progression of renal
      diseases is the inhibition of the renin-angiotensin system, either using
      angiotensin-converting enzyme inhibitors or angiotensin II (Ang II) receptor
      antagonists. In this article, we review the experimental evidences that are
      available on the effects of these treatments on glomerular capillary wall (GCW)
      function. Besides the well-known hemodynamic effects, Ang II antagonism exert
      specific actions on glomerular permeability to water and macromolecules,
      consisting in the elevation of hydraulic permeability and amelioration of
      membrane-sieving function. Experimental investigations of functional and
      structural properties of the glomerular membrane have been performed to discover
      the mechanisms responsible for the protective effects of these treatments. On the
      basis of these observations, we illustrate how Ang II antagonism interfere with
      the complex nature of the glomerular capillary affecting its hemodynamics,
      modulate its cellular components and result in the preservation of GCW function.

PMID- 9001895
TI  - Mechanisms of injury in progressive renal disease.
AB  - Recognition that loss of renal function is progressive has led to extensive
      investigation into risk factors and mechanisms of injury. Persistent activity of
      the underlying disease contributes, though progression may proceed in its
      absence. Nephrotoxic insults which pose little threat to the normal kidney may
      enhance progression in the diseased kidney. Functional adaptations, including
      glomerular hypertension and proteinuria, in themselves contribute to ongoing
      destruction. Structural and cellular adaptations, including tubulointerstitial
      fibrosis, also play a role. A large number of mediators of injury have been
      identified, as well as dietary and metabolic factors which act through these
      mediators and mechanisms. This brief overview will summarize the various
      mechanisms which have been proposed and which are likely to alter clinical
      strategies to slow the progression of renal disease.

PMID- 9001896
TI  - Renal effects of angiotensin II receptor blockade and angiotensin-converting
      enzyme inhibition in healthy subjects.
AB  - The evaluation of a new drug in normotensive volunteers can provide important
      information, as long as the compound has a specific mechanism of action which can
      be evaluated in healthy subjects as well as in patients. The purpose of the
      present paper is to review the renal effects of new specific angiotensin II
      receptor antagonists observed in normotensive subjects and to compare them to
      those of angiotensin-converting enzyme (ACE) inhibitors. Blockade of the renin
      angiotensin system with ACE inhibitors and angiotensin II antagonists induces an
      expected increase in plasma renin activity and plasma angiotensin I levels.
      Plasma angiotensin II levels decrease with ACE inhibitors, whereas they increase
      with angiotensin II receptor blockade. So far, the expected decrease in plasma
      aldosterone levels has been difficult to demonstrate with most angiotensin II
      antagonists. In normotensive subjects, ACE inhibitors, as well as angiotensin II
      antagonists, cause no change in glomerular filtration rate and either no
      modification or an increase in renal blood flow. Both approaches to block the
      renin-angiotensin system are natriuretic, and the natriuresis is more pronounced
      in salt-depleted subjects. Finally, in contrast to ACE inhibitors and other
      angiotensin II receptor antagonist, losartan markedly increases uric acid
      excretion and lowers plasma uric acid levels. This unique property of losartan is
      due to a direct interference of losartan with the uric acid transport system in
      the proximal tubule. The data obtained in normal subjects therefore suggest that
      ACE inhibitors and angiotensin II receptor antagonists have comparable renal
      properties. Whether this is also true in hypertensive patients and in patients
      with proteinuria and chronic renal failure remains to be demonstrated.

PMID- 9001897
TI  - Prognostic value of the short-term antiproteinuric response to ACE inhibition for
      prediction of GFR decline in patients with nondiabetic renal disease.
AB  - In chronic renal disease, the severity of proteinuria is associated with the rate
      of renal function loss. Proteinuria, therefore, was postulated to play a role in
      the final common pathway of chronic renal function loss. If so, reduction of
      proteinuria would improve long-term renal outcome. Improvement of long-term renal
      function outcome has been obtained in several intervention trials; in these
      studies; regimens providing better renoprotection were associated with more
      effective reduction of poteinuria than control regimens. As the reduction of
      proteinuria is mostly associated with a fall in blood pressure, however, it is
      difficult to delineate the respective roles of the lowering of blood pressure and
      of proteinuria. Interestingly, the initial reduction of proteinuria (but not of
      blood pressure) by antihypertensive treatment appears to predict long-term renal
      outcome in man as well as in experimental renal disease. This suggests that an
      intervention strategy aimed not only at the normalization of blood pressure, but
      also specifically at elimination of proteinuria, might be able to improve long
      term renal outcome in proteinuric patients. If so, this would provide further
      evidence in support of the hypothesis that proteinuria is causally involved in
      the progression of long-term renal function loss.

PMID- 9001898
TI  - The renoprotective action of angiotensin-converting enzyme inhibitors in
      diabetes.
AB  - Chronic renal diseases evolve to terminal renal failure by a process leading to
      progressive parenchymal damage which appears relatively independent of the
      initial insult. When glomerular permselectivity is lost, proteins filtered
      through the glomerular capillary, via proximal tubular cell activation and
      upregulation of genes of inflammatory and vasoactive mediators, may give rise to
      an inflammatory reaction that in the long-term can contribute to renal scarring.
      If this interpretation is correct, the best approach to try to retard the
      progression of several renal diseases would be to limit the excessive traffic of
      macromolecules throughout the glomerular capillary by molecules such as the
      angiotensin-converting-enzyme (ACE) inhibitors, which may help restore
      permselective properties to normal. Thus, the present review addresses the
      mechanism(s) of the renal protective effect of ACE inhibitors and analyzes the
      evidence so far available of their salutary effect in human nephropathies, with
      particular focus on diabetic nephropathy.

PMID- 9001899
TI  - Sensitization and reactogenicity of two doses of candidate antileprosy vaccine
      Mycobacterium w.
AB  - M.w vaccine is one of the antileprosy vaccines under test in an ongoing
      comparative vaccine trial in South India. The objective of the present study was
      to examine the sensitizing ability, as measured by skin test reactions to Rees'
      MLSA and lepromin, and reactogenicity of M.w vaccine in the local population. Two
      doses of M.w, 1 x 10(9) bacilli and 5 x 10(9) bacilli, were used, in two separate
      studies of 395 and 400 "healthy" individuals aged 1-65 years. In each study, the
      study subjects received either M.w vaccine or normal saline (control), by random
      allocation. The results showed that healing of vaccination lesions was uneventful
      although the healing process was somewhat prolonged with the higher dose. The
      mean size of lesions was 7.0 mm and 9.5 mm with the low and high doses of the
      vaccine, respectively. The results also showed that M.w vaccine in a dose of 1 x
      10(9) bacilli, failed to induce post-vaccination sensitization as measured by
      reactions to Rees' MLSA and by Fernandez and Mitsuda reactions to lepromin-A.
      However, when the dose of the vaccine was increased to 5 x 10(9) bacilli the mean
      sizes of post-vaccination reactions to Rees' MLSA and lepromin-A (both early and
      late) were significantly larger in the vaccine group compared to that in the
      control group. The sensitizing effect attributable to the vaccine was of the
      order of 1.5 mm to 1.8 mm.

PMID- 9001901
TI  - Leprosy disabilities: magnitude of the problem.

PMID- 9001900
TI  - Serum zinc, copper, magnesium, proteins and superoxide dismutase in leprosy
      patients on multidrug therapy--a follow-up study.
AB  - Serum zinc, copper, magnesium, total proteins and albumin-globulin fractions and
      superoxide dismutase (SOD) were estimated in 80 untreated patients with
      TT/BT/BL/LL type of leprosy and in 40 controls. The investigations were repeated
      on day 30, 60 and 120 after starting multidrug therapy (MDT-WHO) on the patients.
      Serum zinc was significantly lowered in all types of leprosy on days 0 and 30.
      Serum copper was significantly raised in all types of leprosy. This was not
      significant in BT/TT cases on 60, 120 days. There was a correlation between serum
      zinc and copper levels and the severity and type of leprosy. The lowering of
      serum magnesium values were not significant. With therapy, there was a shift of
      all the three elements towards normal values. Serum total proteins reduction was
      not significant. Serum albumin was significantly lowered in all types of leprosy.
      Serum globulin was significantly raised in all types of leprosy. This rise in
      TT/BT was not significant on day 60 and 120 after starting treatment. Serum SOD
      was significantly reduced in all the untreated cases. It gradually increased with
      the clinical improvement under MDT.

PMID- 9001902
TI  - On the criteria for basic elimination of leprosy.

PMID- 9001903
TI  - Immunotherapy of leprosy.
AB  - Immunotherapy aims to modify the defective cell-mediated immune response in a
      section of leprosy cases. This presentation reviews the various immunomodulators
      developed/ investigated for this purpose. Among the various mycobacterial agents,
      BCG, BCG + M.leprae, Mycobacterium w, ICRC bacillus and M.vaccae have been tried
      in leprosy patients and varying degree of beneficial effects on bacterial killing
      and clearance have been observed. Studies carried out at CJIL, Agra and elsewhere
      suggest an important role for these mycobacteria as immunotherapeutic agents.
      Other mycobacteria-M.habana, M.phlei, M.gordonae-have also been reported to be
      promising experimentally. In addition, various drugs such as levamisole, zinc and
      RACA 854 have been observed to have immunomodulatory role in leprosy cases. Other
      promising immunomudlators include transfer factor, interferon gamma, interleukin
      2 and acetoacetylated M.leprae. The progress achieved shows that immunotherapy
      may be considered as adjunct to chemotherapy to enhance bacterial killing as well
      as bacterial clearance and thus may be recommended to shorten the treatment
      period, specially in bacilliferous leprosy cases.

PMID- 9001905
TI  - Involvement of lips and gums in a borderline tuberculoid leprosy patient.

PMID- 9001904
TI  - Leprosy among circus workers.
AB  - Seven (2.31%) circus workers of two circus companies visiting Amritsar were
      detected to be suffering from leprosy. Whether or not they acquired the disease
      during their stay in circus is not so important, but it is necessary to detect
      and treat these itinerant persons. Our experience clearly underlines the
      necessity for undertaking surveys of various workers living in crowded conditions
      (like circus), because of their occupation.

PMID- 9001907
TI  - Hereditary sensory autonomic neuropathy--type II in siblings.

PMID- 9001906
TI  - Thrombocytopenic purpura with blood blisters on once a month rifampicin.

PMID- 9001908
TI  - Wax therapy for dry feet in leprosy.

PMID- 9001910
TI  - Repeat leprosy survey after 7 years in night high schools in greater Bombay.

PMID- 9001909
TI  - Ecological factors in transmission of leprosy.

PMID- 9001911
TI  - The clinical examination of peripheral nerves in leprosy.

PMID- 9001912
TI  - Occupational and environmental medicine in Czech Republic.

PMID- 9001913
TI  - Changes in psychophysiological functions during night shift in nurses. Influence
      of changing from a full-day to a half-day work shift before night duty.
AB  - The effects of changing from a full-day to a half-day shift work before a night
      duty shift on physiological and psychological functions during the night shift
      were investigated in 12 healthy unmarried nurses working on the same ward of a
      university hospital. Three shift patterns, i.e., a day shift following a day
      shift, a night shift following a day shift, and a night shift following a half
      day shift, were studied in terms of physical activity level, sympathetic and
      parasympathetic activity levels, cortisol, prolactin, NK cell activity, and
      changes in mood states. The change to the half-day shift increased the duration
      of sleep before night duty by about 86 min and brought wake-up times forward by
      about 1 h, resulting in increases in rest and time before work. In addition, the
      change was revealed to reduce the influence of reversed-phase circadian rhythms
      on autonomic nervous activity during the night shift. The score for sleepiness
      was significantly lower at 0500 hours following a half-day shift. There were some
      marginal but not significant differences in the scores reflecting the degree of
      vigor, tiredness and irritation during the night shift. Although the prolactin
      concentration was significantly decreased at the start of the night shift after
      the half-day shift, there was no difference in cortisol concentration or NK cell
      activity between the usual night shift after a day shift and the night shift
      after the half-day shift. The half-day shift was not observed to cause any marked
      change in the fixed biorhythms of these nurses. The cortisol and NK cell activity
      levels were low during the night shift, suggesting that the night shift itself is
      a high stress level, which is prejudicial to biodefense.

PMID- 9001915
TI  - In vivo measurements of lead in fingerbone in active and retired lead smelters.
AB  - OBJECT: The aim of this study was to determine the bone lead concentration in
      lead smelters and reference subjects, relate them to the lead concentration in
      blood (B-Pb) and urine (U-Pb), and to use the measured bone lead to calculate a
      biological half-life for lead in bone. METHOD AND DESIGN: The lead concentration
      in the second phalanx of the left index finger (bone-Pb) was determined in vivo
      using an X-ray fluorescence technique. The study population comprised 89 smelters
      with a history of long-term exposure to lead (71 active and 18 retired) and 35
      reference subjects (27 active and 8 retired) with no known occupational exposure
      to lead. Bone-Pb was related to the previous lead exposure, estimated as a time
      integrated B-Pb (CBLI). RESULTS: The retired smelters had the highest bone-Pb
      (median value 55 micrograms/g wet weight, as against 23 micrograms/g in active
      smelters) and 3 micrograms/g in the reference subjects. A strong positive
      correlation was observed between the bone-Pb and the CBLI among both active (rs =
      0.73; P < 0.001) and retired (rs = 0.71; P = 0.001) smelters. The corresponding
      correlations between the bone-Pb and the period of employment were of the same
      magnitude. For retired workers, there were positive correlations between the bone
      Pb and the B-Pb (rs = 0.58; P = 0.011) and U-Pb. (rs = 0.56; P = 0.02). Multiple
      regression analyses showed that bone-Pb was best described by the CBLI, which
      explained 29% of the observed variance (multiple r2) in bone-Pb in active workers
      and about 39% in retired workers. The estimated biological half-life of bone-Pb
      among active lead workers was 5.2 years (95% confidence interval 3.3-13.0 years).
      CONCLUSIONS: The high bone-Pb seen in retired workers can be explained by the
      long exposure periods, the higher exposure levels in earlier decades, and the
      slow excretion of lead accumulated in bone. The importance of the skeletal lead
      pool as an endogenous source of lead exposure in retired smelters was indicated
      by the associations between the B-Pb or U-Pb, on the one hand, and the bone-Pb,
      on the other. In active workers, the ongoing occupational exposure was dominant.
      The in vivo X-ray fluorescence technique is still mainly a research tool, and
      more work has to be done before it can be used more widely in clinical practice.
      However, over the next decade we can anticipate retrospective, prospective and
      cross-sectional epidemiological studies in which bone lead determinations
      reflecting the previous lead exposure in both occupationally and
      nonoccupationally lead exposed populations are related to various types of
      adverse health outcomes. Such studies will improve our knowledge of dose-response
      patterns and provide data that will have an impact on hygienic threshold limit
      values and prevention of lead-induced diseases.

PMID- 9001914
TI  - Occupational chronic exposure to organic solvents. XVI. Ambient and biological
      monitoring of workers exposed to toluene.
AB  - OBJECT: Ambient air and biological monitoring of an occupational toluene exposure
      was carried out on a group of 33 workers. METHOD: The biological monitoring of
      the workers was based on determination of the concentration of toluene in blood
      and on quantification of the urinary metabolites o-cresol and hippuric acid. All
      blood and urine samples were collected post-shift. RESULTS: The average toluene
      concentration in the workplace air was 65 ppm, ranging from 13 to 151 ppm. AN
      average concentration of toluene in the blood of 911 microns/1 was found,
      corresponding to an average urinary concentration of 2.9 mg/1 (2.3 mg/g
      creatinine) o-cresol and 2.4 g/l (1.9 g/g creatinine) hippuric acid. Both urinary
      metabolites can be correlated with the concentration of toluene in ambient air
      and blood, respectively. CONCLUSIONS: The results of our study indicate that the
      determination of the urinary o-cresol excretion represents a diagnostically
      specific and sensitive parameter for the estimation of an individual toluene
      uptake. In contrast, monitoring of the concentration of hippuric acid in urine
      cannot be recommended for assessment of individual exposure. To set up a
      biological tolerance value (BAT) for o-cresol, a urinary concentration of 3 mg/l
      o-cresol should be in accordance with the current MAK value of 50 ppm toluene.

PMID- 9001916
TI  - Potential impact of altitude on lung function.
AB  - OBJECT: The effect of altitude on lung function was evaluated in 21 healthy
      volunteers at 171 m and at 1580 m above sea level. METHOD: Results were obtained
      using an open spirometry system. DESIGN: The parameters analyzed were forced
      vital capacity (FVC), forced expiration volume after 1 s (FEV1), relative 1-s
      capacity (FEV1/FVC), mean expiratory flows at 75%, 50% and 25% of FVC (MEF75,
      MEF50, MEF25), and maximal expiratory flow (peak flow, PEF). RESULTS: MEF75 and
      MEF50 revealed a positive correlation with altitude, with mean rises of 15% and
      11%, respectively. The difference was statistically significant for MEF75 (P =
      0.0009) and MEF50 (P = 0.0001), whereas the other parameters revealed no
      significant difference. CONCLUSION: Altitude could be a variable influencing
      spirometric measurements.

PMID- 9001917
TI  - Chemical degradation of wastes of antineoplastic agents: cyclophosphamide,
      ifosfamide and melphalan.
AB  - Handling genotoxic compounds commonly used in cancer chemotherapy generates
      contaminated wastes that require decontamination before disposal. Chemical
      methods are an alternative and/or a complement to incineration for the treatment
      of wastes and spills. As part of a program initiated by the International Agency
      for Research on Cancer (IARC), three chemical methods readily available in the
      hospital environment, viz sodium hypochlorite (NaOCl, 5.25%), hydrogen peroxide
      (H2O2, < or = 30%) and Fenton reagent (FeCl2, 2H2O; 0.3 g in 10 ml H2O2, 30%),
      were tested for the degradation of three alkylating agents (cyclophosphamide, CP;
      ifosfamide, IF, and melphalan). Pharmaceutical preparations corresponding to the
      most highly concentrated administration solutions in either NaCl (0.9%) or
      dextrose (5%) were inactivated by oxidation volume/volume with each of the
      methods for at least 1 h. The efficiency of degradation was monitored by high
      pressure liquid chromatography. The mutagenicity of the degradation residues was
      tested by means of the Ames test using tester strains of Salmonella typhimurium
      TA 97a, TA 98, TA 100 and TA 102 with and without an exogenous metabolic
      activation system. Complete disappearance of CP was observed after 1 h with all
      degradation methods. However, direct mutagens were generated by the Fenton
      oxidation technique in the presence of dextrose (5%). IF was completely degraded
      by the Fenton reagent and NaOCl methods. No mutagenic residues were detected
      after 1 h of treatment with the Fenton technique, and after 3 h with the NaOCl
      method. Direct-acting mutagens remained after the H2O2 treatment in the presence
      of dextrose (5%). Complete degradation of melphalan was achieved in 1 h by each
      of the three methods, and no mutagenic residues were produced by any of the
      treatments. The use of NaOCl (5.25%) proved the most efficient system for
      degradation of the three alkylating agents.

PMID- 9001918
TI  - Asthma and the indoor environment: the significance of emission of formaldehyde
      and volatile organic compounds from newly painted indoor surfaces.
AB  - As a part of the worldwide European Community Respiratory Health Survey, possible
      relations between asthma and emissions from newly painted indoor surfaces were
      studied. The participants (n = 562) answered a self-administered questionnaire,
      with questions on symptoms and indoor exposures, including indoor painting,
      during the last 12 months. The participants also underwent a structured
      interview, spirometry, peak flow measurements at home (PEF), methacholine
      provocation test for bronchial hyper-responsiveness (BHR), and skin prick tests.
      In addition, serum concentration of eosinophilic cationic protein (S-ECP), blood
      eosinophil count (B-EOS), and total immunoglobulin E (S-IgE) were measured.
      Current asthma was defined as a combination of BHR and at least one asthma
      related symptom (wheezing and attacks of breathlessness). The information
      gathered on indoor painting was compared with exposure measurements of
      formaldehyde and volatile organic compounds (VOC) performed in a selected sample
      of the dwellings (n = 62). Relations between exposures, asthma and clinical signs
      were calculated by multiple linear or logistic regression, adjusting for possible
      influence of age, gender and tobacco smoking. The prevalence of asthma was
      increased among subjects with domestic exposure to newly painted surfaces (OR =
      1.5; 95% CI 1.0-2.4), particularly newly painted wood details (OR = 2.3; 95% CI
      1.2-4.5) and kitchen painting (OR = 2.2; 95% CI 1.1-4.5). Moreover, blood
      eosinophil concentrations were significantly elevated among subjects living in
      newly painted dwellings. A significantly increased prevalence of symptoms related
      to asthma, but not BHR, was observed in relation to workplace exposure to newly
      painted surfaces. The indoor concentration of aliphatic compounds (C8-C11),
      butanols, and 2,2,4-trimethyl 1,3-pentanediol diisobutyrate (TXIB) was
      significantly elevated in newly painted dwellings. The total indoor VOC was about
      100 micrograms/m3 higher in dwellings painted in the last year. A significant
      increase in formaldehyde concentration was observed in dwellings with newly
      painted wood details. Our results indicate that exposure to chemical emissions
      from indoor paint is related to asthma, and that some VOCs may cause inflammatory
      reactions in the airways. To improve asthma management, and to counteract the
      increasing frequency of asthma, the significance of the indoor environment should
      not be neglected. Our study suggests that the contribution of emissions from
      paint to indoor concentrations of formaldehyde and VOCs should be as low as
      possible.

PMID- 9001919
TI  - Effect of 3 hours' passive smoke exposure in the evening on airway tone and
      responsiveness until next morning.
AB  - To study the effect of environmental tobacco smoke (ETS) exposure in the evening
      on nocturnal changes in airway tone and responsiveness, 17 subjects with mild
      asthma (mean +/- SD age, 26 +/- 5 years, FEV1% pred., 89 +/- 14%) were exposed to
      either ambient air (sham) or ETS (20 ppm CO) for 3 h (7:00 to 10:00 p.m.). Seven
      subjects had a history of ETS-induced respiratory symptoms. Spirometry was
      performed 2 h before exposure (5:00 p.m.), every 30 min during exposure, and at
      11:00 p.m., 3:00 a.m., and 7:00 a.m. The provocative concentrations of
      methacholine necessary to decrease FEV1 by 20%, PC20FEV1, were assessed at 5:00
      p.m., 11:00 p.m., 3:00 a.m., and 7:00 a.m. Compared with pre-exposure
      measurements, mean FEV1 values during and after ETS exposure were significantly
      lower than with sham exposure = 0.013 and 0.026). This effect, however, was due
      to a significant response in single individuals. The higher bronchial
      responsiveness after ETS than after sham exceeded one doubling concentration in
      4, 5, and 4 patients at 11:00 p.m., 3:00 a.m., and 7:00 a.m., respectively. The
      opposite effect was observed in 2, 2, and 2 patients, respectively. There was no
      statistically significant mean effect of ETS on airway responsiveness during
      night; however, there was significant heterogeneity in individual responses (P =
      0.0002). Patients with and without a history of ETS-induced symptoms did not show
      different responses to experimental ETS exposure. In conclusion, our data suggest
      that in single adult subjects with mild asthma, acute exposure to ETS in the
      evening can produce a deterioration of airway tone and responsiveness during the
      night, with wide interindividual variability in the response.

PMID- 9001920
TI  - Occupational exposure to sevoflurane and nitrous oxide in operating room
      personnel.
AB  - OBJECT: To quantify the exposure of operating room personnel to sevoflurane and
      nitrous oxide. DESIGN: Prospective study at a university hospital. METHODS: In 25
      patients undergoing elective surgical procedures, anaesthesia was induced with
      thiopentone/etomidate, vecuronium and fentanyl and maintained with fentanyl,
      sevoflurance in 35% oxygen and 65% nitrous oxide (N2O). Occupational exposure to
      sevoflurane and N2O was measured in the breathing zone of one representative of
      each of three personnel groups (anaesthetist, surgeon, auxiliary nurse) by means
      of a direct reading instrument using photoacoustic infrared spectrometry.
      RESULTS: The mean trace concentrations of sevoflurane for the single anaesthetic
      procedures exceeded the 0.5 ppm level in more than 50% of the measurements. The 2
      ppm level was not exceeded in the case of the anaesthetist and the surgeon, but
      was exceeded in 16% of the measurements for the auxiliary nurse. The level of 25
      ppm N2O were exceeded in 28% of the measurements for the anaesthetist and in 16%
      of these for the surgeon and for the auxiliary nurse. CONCLUSIONS: To keep
      exposure low, sevoflurane and N2O were used in a modern working environment: a
      low-leakage anaesthesia machine, high room ventilation rates, scavenging system,
      no intermittent mask ventilation, low to medium concentrations of sevoflurane,
      and strict control of the cuff pressure. Nevertheless, exposure could not be kept
      under NIOSH threshold values in all cases.

PMID- 9001921
TI  - Blood benzene concentrations in workers exposed to oxygenated fuel in Fairbanks,
      Alaska.
AB  - OBJECTIVE: In November 1992 residents of Fairbanks, Alaska became concerned about
      the potential health effects of an oxygenated fuel program during which 15% (by
      volume) methyl tertiary butyl ether (MTBE) was added to gasoline. To address
      those concerns, we earlier completed a survey of occupational exposure to MTBE.
      We conducted a follow-up survey of workers' exposure to benzene from gasoline in
      Fairbanks. DESIGN: Cross-sectional exposure survey. METHODS: We examined blood
      concentrations of benzene from a convenience sample of workers taken in December
      1992 during the oxygenated fuel program and from another convenience sample of
      workers taken in February 1993 after the program was suspended. RESULTS: In
      December, the median blood benzene concentration of samples taken from four
      mechanics after their workshift (postshift) was 1.32 micrograms/l (range, 0.84
      2.61 micrograms/l), and seven nonmechanics (drivers and other garage workers) had
      a median postshift blood benzene concentration of 0.27 microgram/l (range, 0.09
      0.45 microgram/l). In February, nine mechanics had a median postshift blood
      benzene concentration of 1.99 micrograms/l (range, 0.92-3.23 micrograms/l), and
      nine nonmechanics had a median postshift blood benzene concentration of 0.26
      microgram/l (range, 0.2-0.46 microgram/l). CONCLUSION: Mechanics had higher blood
      benzene concentrations than did nonmechanics, but further study is needed to
      determine the impact of the oxygenated fuel program on exposure to benzene.

PMID- 9001922
TI  - Aplastic anemia in a young coke plant worker.
AB  - The objective of this study was to make a contribution to the debate on the cause
      effect relationship between low-dose exposure to benzene and onset of
      hemopathies. We report the case of a coke plant worker suffering from aplastic
      anemia. Before being hired at the coke plant, he underwent a medical examination
      including a blood cell count: no disease or abnormalities of the blood crasis
      were found. For 3 years the patient was then exposed to gas containing-as
      measured in environmental investigation carried out at the coke plant
      concentrations of benzene lower than TLV-TWA ACGIH (measured values 21-109
      micrograms/m3). In the absence from the patient's history of any exposure to
      other myelotoxic agents and of any earlier pathology causing aplastic anemia, we
      assume there is a relationship between exposure to low levels of benzene and
      onset of the disease. However, it is very important to consider that exposure to
      low levels of benzene could promote myelotoxic reactions when the working
      environment contains other substances that may act synergistically or compete for
      the same metabolism sites, or when carcinogenic substances are present in the
      working environment.

PMID- 9001923
TI  - Determination of dimethylhippuric acid isomers in urine by high-performance
      liquid chromatography.
AB  - In order to analyse metabolites in urine after trimethylbenzene (TMB) exposure a
      method based on high-performance liquid chromatography (HPLC) for determination
      of the six dimethylhippuric acids (2,3-DMHA, 2,6-DMHA, 2,5-DMHA, 2,4-DMHA, 3,4
      DMHA and 3,5-DMHA) in urine has been developed. In contrast to earlier published
      methods, the present method allows detection of all possible isomers of DMHA in a
      single analysis. The DMHAs were extracted from urine with dichloromethane. After
      evaporation, the residue was dissolved in mobile phase and analysed by a stepwise
      gradient HPLC system with ultraviolet (UV) detection at 225 nm. Mobile phase A
      (1.25% acetonitrile and 0.3% acetic acid in water) was used up to a retention
      time of 59.5 min and mobile phase B (5% acetonitrile in water containing 0.3%
      acetic acid) was used for completion of the analysis at approximately 90 min. The
      DMHA isomers were chromatographed on a reversed phase Radial-Pak C18 column (4
      microns; 100 mm x 5 mm inner diameter). The detection limit for the six isomers
      was 1.5 micrograms/ml (range 0.5-3.4, 100 microliters injection volume). The
      precision of the method was 4.2% relative standard deviation (range 3.8-4.4; 100
      micrograms/ml). Standard curves of the DMHAs were linear over the interval 10-500
      micrograms/ml in human urine. Individual DMHAs or the sum of DMHA isomers may be
      used as biological indicators of occupational exposure to TMBs.

PMID- 9001925
TI  - Gemcitabine: safety profile unaffected by starting dose.
AB  - Gemcitabine, a novel anticancer agent, has been shown to be active in several
      human solid tumours, including non-small cell lung cancer and pancreatic cancer.
      In addition, gemcitabine has been noted to have a particularly mild safety
      profile for such an active agent and is lacking some of the classical toxicities
      of oncolytics, i.e. alopecia, severe nausea and vomiting, and mucositis.
      Therefore, the safety data from 790 patients in 18 completed clinical studies
      were integrated to study its toxicity profile in more detail. In all of these
      studies gemcitabine was administered as a 30-minute intravenous infusion every
      week for three weeks followed by a week of rest (one cycle). This integrated
      database confirmed that gemcitabine is well tolerated. Its haematological
      toxicity was mild and short lasting. The low incidence of infection was
      correspondingly low. Transaminase elevations occurred frequently, but they were
      usually mild and rarely dose-limiting. Mild proteinuria and haematuria were seen
      but were rarely clinically significant. There was no evidence of cumulative
      hepatic or renal toxicity. Nausea and vomiting were mild, rarely dose-limiting
      and generally well controlled with standard antiemetics. Flu-like symptoms were
      experienced in a proportion of patients but were short-lasting. Where oedema or
      peripheral oedema were experienced, there was no evidence of any association with
      cardiac, hepatic or renal failure. Hair loss was rare. The integrated database
      was also analysed according to starting dose (800, 1000 or 1250 mg/m2) in a
      subset of 665 chemonaive patients to see whether an increased dose resulted in
      increased toxicity. In general, only small, clinically insignificant differences
      in toxicity were seen between the three dose groups. Although segmented
      neutrophil count appeared to increase as starting dose increased (grade 3 or 4,
      19.4%, 23.2%, 28.3% respectively), this was not associated with an increased
      incidence of infection. In some cases, toxicity decreased with increasing dose
      but this may have been because of imbalances between the patient groups. These
      findings indicate that not only is gemcitabine well tolerated, but it also has a
      broad therapeutic index and the use of higher doses may be possible.

PMID- 9001924
TI  - Biochemical activity, pharmacokinetics and tolerability of tepoxalin, a
      cyclooxygenase/5-lipoxygenase inhibitor, in man.
AB  - Tepoxalin, a novel inhibitor of cyclooxygenase (CO) and 5-lipoxygenase (5-LO),
      was investigated for biochemical activity and pharmacokinetics in two studies.
      Study I was a 4-period, double-blind, randomized, single rising dose using 2
      alternating panels (A, B) with interspersed placebo design (A: 25, 100, 400 mg,
      B: 50, 200, 800 mg p.o.). Study II was a 3-panel, randomized, placebo-controlled,
      double-blind, multiple dose study (A: 100 mg, B: 200 mg, C: 400 mg). In both
      studies, CO inhibition was assessed by generation of serum thromboxane (TxB2), 5
      LO activity by LTB4 production ex vivo in Caionophore-stimulated blood. Plasma
      drug concentrations were assayed by HPLC for tepoxalin and its identified acid
      metabolite. It was found in both studies that at all dose levels the TxB2
      generation was markedly suppressed (> 95% 2 h postdose). In study I, at 2 h
      postdose, % inhibition of LTB4 biosynthesis was marginal for the 3 lower doses
      but significant at 200 (14%), 400 (25%) and 800 mg (43%). In study II, the only
      significant inhibition occurred at the 400 mg dose at 6 h postdose on day 1 (17%)
      and on day 8 at 4, 6 and 8 h postdose (32, 42 and 32% respectively). In both
      studies and at all doses, plasma concentrations of tepoxalin varied widely
      between subjects. Linearity between plasma concentrations and dose could not be
      ascertained, and correlation between drug plasma levels and effect on LTB4
      synthesis was poor. Single doses up to 800 mg and multiple doses up to 400 mg of
      tepoxalin were generally well tolerated.

PMID- 9001926
TI  - Equivalence of pharmacokinetic characteristics and bronchodilating effect between
      two combined formulations of nedocromil sodium and salbutamol: MDI and nebulizer
      solution.
AB  - The aim of this study was to determine the equivalence of single doses of two
      nedocromil sodium/salbutamol combined formulations, namely (a) metered dose
      inhaler (MDI) (nedocromil sodium 4 mg + salbutamol 0.2 mg) and (b) nebulizer
      solution (nedocromil sodium 10 mg + salbutamol 1.5 mg), in a group of healthy
      volunteers. The plasma pharmacokinetic profiles of nedocromil sodium and the
      pharmacodynamic effect (bronchodilation) of salbutamol were evaluated. Twelve
      healthy volunteers entered this randomized, cross-over study. All subjects
      completed the pharmacokinetic section of the study. Nine of them completed also
      the pharmacodynamic part of the study. After preliminary controls, treatments
      were administered on separate days and in random order. Blood samples were
      collected 5, 10, 20, 30, 45 min, 1, 1.5, 2, 3 and 4h after test medication.
      Specific airways resistance (sRaw) was measured 5, 10, 20, 30, 40, 50 and 60 min
      following test treatment administration. The pharmacokinetic profiles of
      nedocromil sodium were evaluated using the maximum plasma concentration (Cmax),
      the time to peak plasma concentration (tmax) and the area under the curve from 0
      to infinity (AUCzero-->infinity), derived from the plasma concentration/time
      curves. The bronchodilating effect of the two test treatments were evaluated as
      sRaw percentage change at each time point, maximum sRaw percentage change
      (sRawMAX) and area under the curve (AUC) of sRaw percentage change plotted
      against the time of recording. The mean pharmacokinetic results for MDI and
      nebulizer solution were, respectively: Cmax = 7.59 ng.ml-1 +/- 4.99 and 9.64
      ng.ml-1 +/- 5.22 (p = 0.36), tmax = 0.21 hour +/- 0.08 and 0.28 hour +/- 0.14 (p
      = 0.19), AUCzero-->infinity = 6.28 ng.ml-1.h +/- 2.91 and 12.91 ng.ml-1.h +/-
      4.12 (p = 0.008), while the mean pharmacodynamic results were: sRawMAX = -37.91%
      +/- 13.77 and -39.69% +/- 9.69 (p = 0.69), AUC = -1465.5 delta %.h +/- 799.3 and 
      1683.4 delta %.h +/- 496.3 (p = 0.45). No statistically significant differences
      between treatments were found also for sRaw percentage change at each time point.
      The absorption of nedocromil sodium was proportional to the two administered
      nominal doses and similar to values obtained after administration of nedocromil
      sodium alone. The two combined formulations of nedocromil sodium and salbutamol
      produce an equivalent bronchodilating effect. These results confirm the
      pharmacological equivalence of the two products, whichever may be used according
      to specific therapeutic needs.

PMID- 9001927
TI  - Mechanisms of failure in glaucoma filtering surgery: a consequence of
      antiglaucomatous drugs?
AB  - An increasing number of studies, both experimental and epidemiologic, have
      provided evidence that filtering glaucoma surgery may be less effective than
      initially described. Of a number of risk factors for failure, duration and number
      of antiglaucoma drugs prior to surgery seem to play a critical role and highly
      accumulated antiglaucoma topical treatments significantly reduce success rates.
      Histopathological studies have confirmed that topically applied drugs may exert
      toxic effects to the corneoconjunctival surface, and induce chronic infraclinical
      inflammation, as shown by the presence of immune and inflammatory infiltrates in
      multitreated eyes. The origin of topical inflammation has not yet been clearly
      determined, but a common component of ophthalmic drugs, the benzalkonium chloride
      used as preservative in almost all antiglaucoma preparations, has shown strong
      evidence of toxicity. A number of questions remain to be investigated, but
      suppression of preservatives from chronically applied drugs should be a critical
      issue in the near future.

PMID- 9001928
TI  - Effect of anionic surfactant on the reaction of 2,2(1)-dithiobispyridine with
      bovine oxyhemoglobin as a function of temperature.
AB  - The reaction of bovine oxyhemoglobin with 2,2(1)-dithiobispyridine in the absence
      and presence of sodium n-dodecyl sulphate has been studied as a function of pH
      and temperature. The quantitative analysis of the pH dependence of the apparent
      second order rate constants shows that two ionizable groups are linked to the
      reaction in the native form. These are His HC3 (146) beta and Cys F9 (93) beta.
      Their pKa values are 6.5 and 8.5. In the denatured form, only one ionizable group
      is the modulating factor. This group is Cys F9 (93) beta. Its pKa is 8.35. The
      activation parameters for the reaction of the denatured form of bovine
      oxyhemoglobin with 2,2(1)-dithiobispyridine are lower than those of the native
      form. The reason is that the sulphydryl group is more exposed in the denatured
      form that in the native form. In addition, there is an increase in the rupturing
      of salt bridges and hydrogen bonds between the CO and NH peptide backbone. There
      is also a decrease in van der Waals interactions in the denatured form compared
      to the native form.

PMID- 9001929
TI  - The upper extremity attenuates intermediate frequency vibrations.
AB  - Vibration is related to reports of low back pain; however the biomechanics of
      vibration transmission through the hand-arm system has not been previously
      studied. Vibration was recorded on an accelerometer mounted to a pin
      percutaneously imbedded in the spinous process of L4 of five human subjects. The
      energy was applied through an impact via a pendulum. The subjects adopted an
      erect, relaxed or bent knee posture. The first resonance was 4-6 Hz and the
      second at 9-14 Hz. With the knee bent, the signal was almost completely
      attenuated. If the impact was applied through a handle and the hand-arm system
      there was complete attenuation.

PMID- 9001930
TI  - Residual strength of equine bone is not reduced by intense fatigue loading:
      implications for stress fracture.
AB  - Fatigue or stress fractures are an important clinical problem in humans as well
      as racehorses. An important question in this context is, when a bone experiences
      fatigue damage during extreme use, how much is it weakened compared to its
      original state? Since there are very limited data on this question and stress
      fractures are common in racehorses, we sought to determine the effect of fatigue
      loading on the monotonic strength of equine cortical bone. Beams were machined
      from the dorsal, medial and lateral cortices of the third metacarpal bones of six
      thoroughbred racehorses. Beams from left and right bones were assigned to control
      and fatigue groups, respectively (N = 18 each). The fatigue group was cyclically
      loaded in three-point bending at 2 Hz for 100,000 cycles at 0-5000 microstrain
      while submerged in saline at 37 degrees C. These beams, as well as those in the
      control group, were then monotonically loaded to failure in three-point bending.
      The monotonic load-deflection curves were analyzed for differences using three
      factor (fatigue loading, anatomic region, and horse) analysis of variance. The
      mean failure load was 3% less in the fatigue group, but this reduction was only
      marginally significant. Neither elastic modulus nor yield strength was
      significantly affected by the fatigue loading. The principal effects of fatigue
      loading were on post-yield behavior (yield being based on a 0.02% offset
      criterion). The work done and the load increase between yield and failure were
      both significantly reduced. All the variables except post-yield deflection were
      significantly affected by anatomic region. In summary, loading equivalent to a
      lifetime of racing does not significantly weaken equine cortical bone ex vivo.
      The clinical implication of this may be that the biological repair of fatigue
      damage can actually contribute to stress fracture if pressed too far.

PMID- 9001931
TI  - Minimum energy trajectories of the swing ankle when stepping over obstacles of
      different heights.
AB  - This study was performed to test the hypothesis that the motion of the lower
      extremities when stepping over obstacles is governed by the criterion of minimum
      mechanical energy. The trajectories of the swing ankle during level walking and
      when stepping over obstacles of 51, 102, 153, and 204 mm heights were predicted
      and measured for eight healthy young adults. The predictions were made with a
      planar, seven-link linkage model based on the criterion of minimum mechanical
      energy using the method of dynamic programming. When stepping over obstacles, the
      predicted trajectories of the swing ankle were just high enough for the swing toe
      to clear the obstacles. The clearances measured between the obstacle and toe were
      significantly larger than those predicted. When stepping over obstacles the
      levels of work required to generate the measured trajectories were significantly
      larger (p < or = 0.002) than those required to produce the predicted
      trajectories. The amount of work necessary to generate the measured or predicted
      trajectories increased linearly (significant at p < or = 0.022) with obstacle
      height and, except when predicting the trajectory for the lowest obstacle, was
      significantly greater than that required when walking on level ground (p < 0.02).
      Thus, conservation of energy was found to become a less dominant criterion for
      governing the motion of the body when crossing obstacles than when walking on
      level ground.

PMID- 9001932
TI  - Analysis of cementless implants using interface nonlinear friction--experimental
      and finite element studies.
AB  - Measured interface nonlinear friction properties are used to develop models to
      study the short-term fixation response of smooth- and porous-surfaced posts, bone
      screws, and plates fixed with and without posts/screws. Experimental studies are
      carried out to validate the model predictions and identify the relative role of
      posts and screws in fixation of a plate on a polyurethane block under
      symmetric/eccentric axial compression loads. The idealized Coulomb's friction is
      also used for the sake of comparison. The incorporation of measured nonlinear,
      rather than the idealized Coulomb, friction is essential to compute realistic
      results. For plate fixation, the experimental and finite element results show
      that the screw fixation yields the stiffest response followed by the smooth- and
      then porous-coated post fixation. For example, under 1000 N eccentric axial
      compression, the edge of the plate opposite the loaded edge is measured to lift
      by 1147 +/- 72, 244 +/- 38, or 112 +/- 28 microns, respectively, for the cases
      with no fixation, with smooth-surfaced posts, or with screws. The corresponding
      models predict, respectively, values of 1538, 347, or 259 microns and also 556
      microns for the plate fixed with porous coated posts. The satisfactory agreement
      between numerical and experimental results confirms the importance of proper
      interface modelling for the analysis of posts, screws, and complex fixation
      systems. This becomes further evident when considering cementless implants in
      which the bone-implant interface exhibits relatively large displacements as the
      maximum resistance force is reached. The developed models can be used to
      investigate the post-operative short-term stability of various cementless implant
      designs.

PMID- 9001933
TI  - Tractive forces during rolling motion of the knee: implications for wear in total
      knee replacement.
AB  - Wear at the polyethylene tibial plateau in total knee arthroplasty (TKR) is one
      of the primary concerns with these devices. The artificial bearing of a TKR has
      to sustain large forces while allowing the mobility for normal motion, typically,
      rolling, gliding and rotation. The tractive forces during the rolling motion at
      the knee joint were analyzed to determine which factors cause these forces to
      increase in TKR. The implications of these tractive forces to polyethylene wear
      were considered. Traction forces were calculated using a model of the knee to
      evaluate the effect of variations in the coefficient of friction, gait
      characteristics, antagonistic muscle contraction and patellofemoral mechanics.
      The model was limited to the sagittal plane motion of the femur on the tibia. The
      input for the model was the shape of the articulating surface, coefficient of
      friction, contact path, muscle anatomy and gait kinetics common to patients with
      a total knee replacement. The generation of tractive forces on the tibial
      polyethylene plateau was highly dependent on the static and dynamic coefficient
      of friction between the femur and the tibia. A peak tractive force of
      approximately 0.4 body weight was calculated with a peak normal force of 3.3 body
      weight. Tractive rolling occurred during most of stance phase when the static
      coefficient was 0.2. Alterations in gait patterns had a substantial effect on the
      generation of tractive forces at the knee joint. When an abnormal gait pattern
      (often seen following TKR) was input to the model the posteriorly directed
      tractive force on the tibial surface was reduced. It was also found that
      variations in muscle contractions associated with antagonistic muscle activity as
      well as the angle of pull of the patellar tendon affected the magnitude of
      tractive forces. The results of the study suggest that there are feasible
      conditions following total knee replacement which can lead to tractive forces
      during rolling motion at the tibiofemoral articulation that should be considered
      in the analysis of factors leading to polyethylene damage in total knee
      replacement.

PMID- 9001934
TI  - An inverse dynamics modeling approach to determine the restraining function of
      human knee ligament bundles.
AB  - During knee motion, the fiber bundles of ligaments are nonuniformly loaded in a
      recruitment pattern which is different for successive knee-joint positions. As a
      result, the restraining functions of these ligaments are variable. To analyze the
      relative restraint contributions of the fiber bundles in different knee-joint
      positions, a new method was developed. Its application was illustrated for the
      cruciate ligaments of one knee-joint specimen. The methods developed to estimate
      bundle forces comprise five steps. First, the three-dimensional motions of a knee
      specimen are measured for anterior-posterior forces, using Rontgen
      Stereophotogrammetric Analysis. Second, bone-ligament-bone tensile tests are
      performed to evaluate the mechanical properties of these structures in several
      relative orientations of the bones. Third, multiple fiber bundles are identified
      in each ligament, based on the main fiber orientations. Fourth, the nonlinear
      force-length relationship of each functional bundle, as defined by a stiffness
      and a recruitment parameter, is determined by combining the multidirectional
      tensile tests with a multiline-element ligament model. Finally, the information
      obtained is combined in a whole-joint computer model of the knee, to determine
      the internal forces in the initial kinematic experiment, using an inverse
      dynamics approach. The technique appeared to be extremely time consuming and
      technologically involved. However, it was demonstrated to be useful and
      effective. The preliminary results reveal that the fiber bundle restraints are
      extremely sensitive to the knee flexion angle and the restraining forces are
      highly variable within the ligaments. For both cruciate ligaments, a gradual
      transition was demonstrated in load transfer from the posterior bundles to the
      more anteriorly positioned ones during knee flexion. Furthermore, it appeared
      that relatively high forces were carried by only a few fiber bundles at each
      flexion angle. Based on these preliminary results, it is concluded that the
      determination of forces in multiple ligament bundles is important for the
      understanding of failure mechanisms of ligaments. In particular, alternate
      loading of different fiber bundles suggests that successful operative
      reconstruction of the cruciate ligaments may not be achieved simply by a one
      bundle preparation.

PMID- 9001935
TI  - Trabecular bone adaptation to variations in porous-coated implant topology.
AB  - Trabecular bone adaptation adjacent to porous-coated platen implants embedded
      within canine distal femoral metaphyses was evaluated following 24 weeks of daily
      compressive loading. The in vivo experimental model delivered controlled loads to
      five different platen implant topologies with variations in platen shape and
      porous coating distribution. Adaptive changes were evaluated based on three
      dimensional stereological analyses of trabecular bone architecture underneath
      each platen and non-destructive mechanical tests of platen construct stiffness.
      Fully coated cylindrical platen designs possessed the highest construct stiffness
      in both tension and compression. Changes in local trabecular bone morphology were
      also found to be significantly influenced by platen implant topology. Cylindrical
      platens with fully coated bottom surfaces were associated with greater decreases
      in trabecular bone volume and connectivity than cylindrical platens with smooth
      bottom surfaces or fully coated conical platens. Comparisons to site-matched
      contralateral control bone volumes across all platen designs indicated
      significant decreases in the average bone volume fraction, trabecular plate
      number, and connectivity within experimental samples, but no change in trabecular
      plate thickness. In addition, analyses of microstructural anisotropy revealed a
      20 degrees or 20.2 degrees trabecular reorientation towards the axis of loading
      in experimental tissue. This study demonstrates that trabecular bone adaptation
      near porous-coated surfaces is influenced by variations in local implant topology
      and provides insight into specific mechanisms of implant-mediated microstructural
      adaptation.

PMID- 9001936
TI  - Scanning electron microscopy of human cortical bone failure surfaces.
AB  - Undecalcified samples extracted from human femoral shafts are fractured by
      bending and the fracture surfaces are examined with a scanning electron
      microscope (SEM). The investigation is performed on both dry and wet (hydrated
      with a saline solution) specimens. SEM micrographs show patterns in many respects
      similar to those observed in fractography studies of laminated fiber-reinforced
      synthetic composites. In particular, dry and wet samples behave like brittle and
      ductile matrix laminates, respectively. An analysis carried out on the basis of
      the mechanisms that dominate the fracture process of laminates shows that a
      reasonable cortical bone model is that of a laminated composite material whose
      matrix is composed of extracellular noncollagenous calcified proteins, and the
      reinforcement is constituted by the calcified collagen fiber system.

PMID- 9001937
TI  - A musculoskeletal model of the knee for evaluating ligament forces during
      isometric contractions.
AB  - A model of the knee in the sagittal plane was developed to study the forces in
      the ligaments induced by isometric contractions of the extensor and flexor
      muscles. The geometry of the distal femur was obtained from cadaver data. The
      tibial plateau and patellar facet were modeled as flat surfaces. Eleven elastic
      elements were used to describe the mechanical behavior of the anterior and
      posterior cruciate ligaments (ACL and PCL), the medial and lateral collateral
      ligaments (MCL and LCL), and the posterior capsule. The model knee was actuated
      by 11 musculotendinous units, each muscle represented by a Hill-type contractile
      element, a series-elastic element, and a parallel-elastic element. Tendon was
      assumed to be elastic. The response of the model to anterior-posterior drawer
      suggests that the geometrical and mechanical properties of the model ligaments
      approximate the behavior of real ligaments in the intact knee. Calculations for a
      simulated quadriceps leg raise indicate further that the two-dimensional model
      reproduces the response of the three-dimensional knee under similar conditions of
      loading and constraint. During maximum isometric contractions of the quadriceps,
      the model ACL is loaded from full extension to 80 degrees C of flexion; the model
      PCL is loaded at 70 degrees of flexion and greater. For maximum isometric
      extension, ACL forces in the range 0-20 degrees of flexion depend most heavily
      upon the force-length properties of the quadriceps. At flexion angles greater
      than 20 degrees, cruciate ligament forces are determined by the geometry of the
      articulating surfaces of the bones. During isolated contractions of the
      hamstrings and gastrocnemius muscles, the model ACL is loaded from full extension
      to 10 degrees of flexion; the model PCL is loaded at all flexion angles greater
      than 10 degrees. Isolated contractions of the flexor muscles cannot unload the
      ACL near full extension, as the behavior of the ACL in this region is governed by
      the shapes of the bones. At 10 degrees of flexion or greater, the overall pattern
      of PCL force is explained by the force length properties of the hamstrings and by
      the geometrical arrangement of the flexor muscles about the knee.

PMID- 9001938
TI  - A computer model with surface friction for the prediction of total knee
      kinematics.
AB  - A computer model was generated which modelled the bearing surfaces of total
      knees, and predicted the kinematics for a set of input forces and moments. The
      model included friction at the bearing surfaces and soft tissue restraint forces,
      including the effect of cruciate resection. Predictions from the model were
      compared with data from a Knee Simulating Machine. There was close agreement in
      the shapes of the curves and in the magnitudes of the displacements and rotations
      under most conditions. The model predicted major differences in kinematics when
      friction between metal and polyethylene was included, the differences being even
      greater at the friction levels associated with small embedded acrylic particles.
      Soft tissue restraint was shown to reduce the displacements and rotations for
      tibial surfaces of low constraint but for moderate to high constraint, the soft
      tissues affected the kinematics only slightly. When the model was used to predict
      the motions for different condylar geometries, widely different contact paths on
      the tibial surface were determined. This suggested that condylar geometries which
      appeared to be generally similar, could have important differences in kinematics,
      function and wear.

PMID- 9001939
TI  - Artifactual nonlinearity due to wear grooves and friction in four-point bending
      experiments of cortical bone.
AB  - Experiments and analyses were performed to determine the cause of a nonlinear
      force-deflection response observed in four-point flexural fatigue of beams of
      cortical bone machined from the mid-diaphysis of the equine third metacarpus.
      Observable grooves which formed on the beam surface at supports and load noses
      were found to be the primary cause of the nonlinearity. An additional geometric
      nonlinearity at large deflections revealed by finite element modeling may be
      minimized by using the smallest diameter supports and load noses recommended in
      ASTM 790. However, frictional constraint of the beams at the load noses and
      supports can occur at low load levels and should be avoided by using roller
      bearing supports and load noses, or some equivalent method.

PMID- 9001940
TI  - Measurements of active myocardial tension under a wide range of physiological
      loading conditions.
AB  - Active tension developed while cardiac muscle shortens has been studied
      extensively under afterloaded isotonic or isovelocity conditions. However, these
      are not true in vivo loading conditions. To obtain more physiological loading, we
      controlled sarcomere length to follow the time courses that we observed
      previously in a beating canine left ventricle. Sarcomere length was measured by
      laser diffraction in 12 rat cardiac trabeculae, superfused with Krebs-Henseleit
      solution (25 degrees C; [Ca] = 1.5 mM). Force was measured by a silicon strain
      gauge. Sarcomere length time courses were scaled slightly in time to account for
      temperature and species differences. We examined the relationships between active
      tension and sarcomere length under loading observed over a wide range of left
      ventricular preloads and afterloads, and at two sites. Under all loading
      conditions, active tension was not isotonic but declined steadily throughout the
      ejection period. While there were major differences in peak tension dependent on
      loading conditions and the incidence of 'pre-ejection' sarcomere shortening,
      these factors did not influence the relationship between sarcomere length and
      peak active tension. This study provides excellent illustrations of the potential
      differences in stress (1) within a ventricular wall, and (2) under different
      operating conditions. Moreover, it provides data for developing models of fiber
      contraction to be synthesized into a whole heart for predicting potential
      differences in stress at all sites and under all loading conditions.

PMID- 9001941
TI  - Statically equivalent load and support conditions produce different hip joint
      contact pressures and periacetabular strains.
AB  - The hip is a common site of orthopaedic trauma and disease, and considerable
      research has been directed toward understanding the development of contact
      pressures within the joint. Virtually all experimental studies to date have
      employed proximal femurs compressed along the joint reaction force vector into
      acetabulae explanted from cadaver pelves. This approach presumes that
      deformations of the acetabulum are highly localized, and that the pelvis is
      functionally a rigid body. We have developed a methodology that uses intact
      pelves loaded through simulation of the abductor mechanism. A direct comparison
      of the two techniques revealed significantly different joint contact
      characteristics and periacetabular strains. Fuji film measurements of contact
      area and pressure were more widely distributed across the acetabulum for the
      intact pelvis, with significant pressure development in anterior and posterior
      regions. Contact patterns in the explanted acetabulae were concentrated in the
      superior portion of the joint. Principal strains from three rosette gages placed
      near the acetabular rim were also significantly different for the two testing
      techniques, but were not substantially altered by the presence of Fuji film
      within the joint. The results indicate that deformation of the entire pelvis and
      the manner in which loads are applied significantly affect development of contact
      pressures within the hip joint, and that Fuji film is a suitable technique for
      recording those patterns.

PMID- 9001942
TI  - Numerical conversion of transient to harmonic response functions for linear
      viscoelastic materials.
AB  - Viscoelastic material behavior is often characterized using one of the three
      measurements: creep, stress-relaxation or dynamic sinusoidal tests. A two-stage
      numerical method was developed to allow representation of data from creep and
      stress-relaxation tests on the Fourier axis in the Laplace domain. The method
      assumes linear behavior and is theoretically applicable to any transient test
      which attains an equilibrium state. The first stage numerically resolves the
      Laplace integral to convert temporal stress and strain data, from creep or stress
      relaxation, to the stiffness function, G(s), evaluated on the positive real axis
      in the Laplace domain. This numerical integration alone allows the direct
      comparison of data from transient experiments which attain a final equilibrium
      state, such as creep and stress relaxation, and allows such data to be fitted to
      models expressed in the Laplace domain. The second stage of this numerical
      procedure maps the stiffness function, G(s), from the positive real axis to the
      positive imaginary axis to reveal the harmonic response function, or dynamic
      stiffness, G(j omega). The mapping for each angular frequency, s, is accomplished
      by fitting a polynomial to a subset of G(s) centered around a particular value of
      s, substituting js for s and thereby evaluating G(j omega). This two-stage
      transformation circumvents previous numerical difficulties associated with
      obtaining Fourier transforms of the stress and strain time domain signals. The
      accuracy of these transforms is verified using model functions from
      poroelasticity, corresponding to uniaxial confined compression of an isotropic
      material and uniaxial unconfined compression of a transversely isotropic
      material. The addition of noise to the model data does not significantly
      deteriorate the transformed results and data points need not be equally spaced in
      time. To exemplify its potential utility, this two-stage transform is applied to
      experimental stress relaxation data to obtain the dynamic stiffness which is then
      compared to direct measurements of dynamic stiffness using steady-state
      sinusoidal tests of the same cartilage disk in confined compression. In addition
      to allowing calculation of the dynamic stiffness from transient tests and the
      direct comparison of experimental data from different tests, these numerical
      methods should aid in the experimental analysis of linear and nonlinear material
      behavior, and increase the speed of curve-fitting routines by fitting creep or
      stress relaxation data to models expressed in the Laplace domain.

PMID- 9001943
TI  - A controlled-release ergometer for the human ankle.
AB  - A hydraulic ergometer for the human foot is described that can apply ankle
      rotations up to 1 rad at a constant high speed of 10-20 rad/s against moments up
      to 200 N m. The initial acceleration is damped, so as not to exceed a preset
      value. With the presented set-up the series elasticity of the intact human m.
      triceps surae can be measured.

PMID- 9001944
TI  - Ischemic disruption of glutamate homeostasis in brain: quantitative
      immunocytochemical analyses.
AB  - More than 10 years ago, it was shown by microdialysis that the excitatory
      transmitter glutamate accumulates in the interstitial space of brain subjected to
      ischemic insult. This was one of the key observations leading to the formulation
      of the "glutamate hypothesis' of ischemic cell death. It is now assumed that even
      a transient glutamate overflow may set in motion a number of events that
      ultimately cause cell loss in vulnerable neuronal populations. The aim of the
      present review is to discuss the intracellular changes that underlie the
      dysregulation of extracellular glutamate during and after ischemia, with emphasis
      on data obtained by postembedding, electron microscopic immunogold cytochemistry.
      While the time resolution of this approach is necessarily limited, it can reveal,
      quantitatively and at a high level of spatial resolution, how the intracellular
      pools of glutamate and metabolically related amino acids are perturbed during and
      after an ischemic insult. Moreover, this can be done in animals whose
      extracellular amino acid levels are monitored by microdialysis, allowing a direct
      correlation of extra- and intracellular changes. Immunogold analyses of brains
      subjected to ischemia have identified dendrites and neuronal somata as likely
      sources of glutamate efflux, probably mediated by reversal of glutamate uptake.
      The vesicular glutamate pool has been found to be largely unchanged after 20 min
      of ischemia. Ischemia causes an increased glutamate content and an increased
      glutamate/glutamine ratio in glial cells, as revealed by double immunogold
      labelling. This argues against the idea that glial cells contribute to the
      extracellular overflow of glutamate in the ischemic brain.

PMID- 9001945
TI  - NGF prevents further atrophy of cholinergic cells of the nucleus basalis due to
      cortical infarction in adult post-hypothyroid rats but does not restore cell size
      compared to euthyroid [correction of euthroid] rats.
AB  - We have tested the hypotheses that nerve growth factor treatment in adult post
      hypothyroid rats can: (1) restore cross-sectional area of cholinergic cells of
      the nucleus basalis and (2) prevent further atrophy of these neurons following
      cortical infarction. In addition, we assessed the expression of p75NGFR and
      p140trkA mRNAs in the nucleus basalis cells of post-hypothyroid rats. Rats were
      rendered hypothyroid by the addition of propylthiouracil to their diet beginning
      on embryonic day 19 until the age of 1 month. At this time both the pups and
      their dams continued to receive 0.05% propylthiouracil in their diet and the pups
      were thyroidectomized. At 60 days, propylthiouracil treatment was interrupted and
      thyroxine levels were restored to normal by daily subcutaneous administration of
      physiological levels of thyroxine. Morphometric analysis identified atrophied
      nucleus basalis magnocellularis cholinergic cells at two ages, days 75 and 105,
      identified by in situ hybridization for p75NGFR and p140trkA mRNAs in methylene
      blue stained cells (day 75) and choline acetyltransferase immunostaining (day
      105). The mean number of silver grains (pixels) per microns2 (mean +/- S.E.M.) of
      cell body cross-sectional area for p75NGFR mRNA in the nucleus basalis
      magnocellularis of euthyroid rats was 3.43 +/- 0.89, which was not statistically
      different from post-hypothyroid animals (4.02 +/- 1.07). A similar finding was
      noted for p140trkA mRNA: mean number of grains in the euthyroid group was 5.54 +/
      0.96 and was not statistically different from the post-hypothyroid group (6.32
      +/- 1.45). Nerve growth factor treatment in adulthood (between days 75 and 82)
      did not restore cross-sectional area from early thyroid deprivation. However, it
      prevented further atrophy of nucleus basalis magnocellularis neurons following
      cortical devascularization inflicted in adulthood (day 75).

PMID- 9001946
TI  - Estrogen regulation of preproenkephalin messenger RNA in the forebrain of female
      mice.
AB  - We studied the effects of 10 micrograms of 17-beta-estradiol-3-benzoate treatment
      on preproenkephalin (PPE) mRNA expression in female ovariectomized (OVX) Swiss
      Webster mice after 0, 1, 6, 12, 24, or 48 h, using the in situ hybridization
      technique. The VMH showed a 1.6- and 3.3-fold increase in PPE mRNA levels after
      24 and 48 h of estrogen treatment (respectively) when compared to OVX females. No
      differences at 1, 6 or 12 h of estrogen treatment groups were observed compared
      to control groups. PPE mRNA levels were also increased at 24 and 48 h after
      estrogen treatment in the posterior medial nucleus of the amygdala (MeAmyg) by
      3.3- and 2.5-fold, respectively, and in the arcuate nucleus (ARC) by 2- and 1.9
      fold, respectively. No effects of estrogen were observed on PPE mRNA levels in
      the caudate-putamen (CPu) or the posterior lateral cortical nucleus of the
      amygdala (plCoAmyg). Furthermore, basal levels of PPE mRNA expression in the VMH
      and MeAmyg of female mice were lower than those observed in rats, although levels
      in the CPu, plCoAmyg, and ARC were similar between females of the two species. In
      conclusion, we have found two differences between the species. First, Swiss mice
      demonstrated a slower time course of estrogen induction of PPE mRNA in the VMH,
      ARC. and MeAmyg compared to female rats. Second, there are differences in basal
      levels of PPE in the MeAmyg and VMH.

PMID- 9001947
TI  - Dopaminergic transmission in the rat retina: evidence for volume transmission.
AB  - The study was designed to determine whether dopaminergic neurotransmission in the
      retina can operate via volume transmission. In double immunolabelling
      experiments, a mismatch as well as a match was demonstrated in the rat retina
      between tyrosine hydroxylase (TH) and dopamine (DA) immunoreactive (ir) terminals
      and cell bodies and dopamine D2 receptor-like ir cell bodies and processes. The
      match regions were located in the inner nuclear and plexiform layers (D2 ir cell
      bodies plus processes). The mismatch regions were located in the ganglion cell
      layer, the outer plexiform layer, and the outer segment of the photoreceptor
      layer, where very few TH ir terminals can be found in relation to the D2 like ir
      processes. In similar experiments analyzing D1 receptor like ir processes versus
      TH ir nerve terminals, mainly a mismatch in their distribution could be
      demonstrated, with the D1 like ir processes present in the outer plexiform layer
      and the outer segment where a mismatch in D2 like receptors also exists. The
      demonstration of a mismatch between the localization of the TH terminal plexus
      and the dopamine D2 and D1 receptor subtypes in the outer plexiform layer, the
      outer segment and the ganglion cell layer (only D2 immunoreactivity (IR))
      suggests that dopamine, mainly from the inner plexiform layer, may reach the D2
      and D1 mismatch receptors via diffusion in the extracellular space. After
      injecting dopamine into the corpus vitreum, dopamine diffuses through the retina,
      and strong catecholamine (CA) fluorescence appears in the entire inner plexiform
      layer and the entire outer plexiform layer, representing the match and mismatch
      DA receptor areas, respectively. The DA is probably bound to D1 and D2 receptors
      in both plexiform layers, since the DA receptor antagonist chlorpromazine fully
      blocks the appearance of the DA fluorescence, while only a partial blockade is
      found after haloperidol treatment which mainly blocks D2 receptors. These results
      indicate that the amacrine and/or interplexiform DA cells, with sparse branches
      in the outer plexiform layer, can operate via volume transmission in the rat
      retina to influence the outer plexiform layer and the outer segment, as well as
      other layers of the rat retina such as the ganglion cell layer.

PMID- 9001948
TI  - Retinal and non-retinal inputs upon retinopetal RMA neurons in the lamprey: a
      light and electron microscopic study combining HRP axonal tracing and GABA
      immunocytochemistry.
AB  - A light and electron microscopic study, combining HRP axonal tracing or
      degeneration and GABA immunocytochemistry, was performed in the lamprey Lampetra
      fluviatilis in order to analyze retinal and non-retinal inputs upon the
      retinopetal neurons localized in the reticular mesencephalic area (RMA). The
      iontophoretic deposit of HRP onto the central stump of the cut optic nerve
      produced a dense anterograde labeling in the retino-recipient strata marginale
      and cellular externum of the optic tectum as well as the retrograde labeling of
      retinopetal neurons in the mesencephalic tegmentum. The large ascending proximal
      dendrites of the retinopetal neurons constituted a distinct bundle coursing first
      dorso-laterally in the dorsal mesencephalic tegmentum, and then dorso-medially in
      the strata fibrosum centrale and cellulare et fibrosum internum of the optic
      tectum before their distal portions penetrated the retino-recipient tectal
      layers. The distribution of GABA immunoreactivity was also investigated in the
      tectal layers and dorsal mesencephalic tegmentum with both pre- and post
      embedding methods. The retinal terminals, identified either following HRP
      iontophoresis in the optic nerve or in early phases of degeneration after short
      term survivals following retinal lesion, contained rounded-shaped synaptic
      vesicles and were always GABA immunonegative. They established asymmetrical
      synaptic contacts on the distal dendrites of RMA neurons and represented 11.4% of
      all terminals contacting such neurons (15% of these neurons were GABA
      immunopositive). The dense extra-retinal input upon the retinopetal RMA neurons
      was composed of five types of axon terminal profiles, either GABA-immunopositive
      or -immunonegative. Considering the different cytochemical types of axon
      terminals contacting RMA neurons, as well as the characteristics of the retinal
      targets of these neurons, we suggest that, globally, the effects of RMA neurons
      upon the retina are mainly inhibitory.

PMID- 9001950
TI  - Bioanalysis of beta 2-agonists by hyphenated chromatographic and mass
      spectrometric techniques.
AB  - Recent reports on the misuse of beta 2-agonists, both as stimulants and as
      "anabolic agents" in sports, highlight the importance of screening and
      confirmation methods for these compounds in anti-doping control procedures.
      Although only a few analytical methods have been developed for this purpose, the
      large experience gained, both in pharmacokinetic studies and above all in the
      control of the residues of beta 2-agonists in animal fluids and tissues, can be
      of great help in the anti-doping field. This paper reviews single-residue (SR)
      and multi-residue (MR) methods developed for the analysis of beta 2-agonists in
      urine, plasma and hair samples, based on hyphenated chromatographic and mass
      spectrometric techniques, published in the last ten-year period. The evolution
      from GC-MS analysis after derivatization, with particular attention to the
      features of different proposed derivatives, to the most recent applications of
      coupled-column liquid chromatography (LC-LC) combined with tandem mass
      spectrometric detection (MS-MS) via a thermospray (TSP) interface is illustrated,
      and future perspectives in the field are outlined.

PMID- 9001949
TI  - Testing for natural and synthetic anabolic agents in human urine.
AB  - This paper describes a comprehensive method for the detection of natural and
      synthetic anabolic agents, including some veterinary preparations such as
      trenbolone, zeranol (a non-steroidal agent) and clenbuterol (a beta 2-agonist).
      For the natural steroids such as testosterone, the precise determination of
      urinary androgens during routine procedures allowed the description of
      statistical distribution of relevant parameters of the endogenous steroid profile
      amongst male athletes. The validity of the results is discussed, taking into
      account some factors that may cause the degradation of the specimen.

PMID- 9001952
TI  - Increased urinary testosterone/epitestosterone ratios found in Swedish athletes
      in connection with a national control program. Evaluation of 28 cases.
AB  - In connection with a national anti-doping control program, including analysis of
      8946 urine samples, 28 athletes were found to have delivered samples free from
      xenobiotic anabolic steroids but with an increased testosterone/epitestosterone
      (T/E) ratio (> 6). Unannounced testing of the above athletes produced 2-4
      additional urine samples during the next 2-3 months. A low degree of variation of
      the T/E ratio, with a C.V. below 30% was found in 17 of the subjects whereas 10
      had a C.V. varying from 31% to 43%. One subject with a high urinary T/E ratio
      (10.5) had a C.V. of this ratio of 126% and also an extremely high ratio between
      testosterone and LH in urine. It has been reported that non-users of testosterone
      have T/E ratios fluctuating around a mean with a C.V. that will not exceed 30%.
      We found that administration of testosterone to seven healthy volunteers resulted
      in urinary T/E ratios that varied with a C.V. ranging from 67% to 130% during the
      following 4 weeks. It is concluded that among the above 28 cases, only one can be
      regarded as a clear case of testosterone doping. Although the vast majority of
      Swedish athletes have urinary T/E ratios below six, there is a subfraction with a
      constant higher ratio, possibly due to genetic factors.

PMID- 9001953
TI  - Direct measurement of steroid sulfate and glucuronide conjugates with high
      performance liquid chromatography-mass spectrometry.
AB  - Direct detection of several steroid glucuronide and sulfate conjugates was
      achieved with electrospray reversed-phase HPLC-mass spectrometry. Separation of
      steroid 17-OH or 5-H epimers conjugated with glucuronide or sulfate could be
      achieved using gradient elution. Testosterone glucuronide, testosterone sulfate,
      epitestosterone sulfate and epitestosterone glucuronide were chromatographically
      resolved, although significant variation in solvent strength was observed between
      methanol and acetonitrile. Positive ionization mode MS and MS-MS spectra were
      employed to obtain both quantitative and structural information. Some differences
      were noted with respect to steroid structure and adduct formation, including
      significant differences in the stability of epimers in the declustering region of
      the interface. Negative ionization mode, although having lower limits of
      detection, did not provide useful structural information in either the MS or MS
      MS mode. Using a packed capillary column (300 microns I.D.), a detection limit of
      25 pg was achieved for epitestosterone glucuronide.

PMID- 9001954
TI  - Separation and confirmation of anabolic steroids with quadrupole ion trap tandem
      mass spectrometry.
AB  - Gas chromatography-mass spectrometry (GC-MS) is the method of choice for
      separation and detection of anabolic steroids in urine. Recently, there have been
      advances in the areas of gas chromatography columns, tandem mass spectrometry
      using ion traps, and large volume sample injection that have promise for lowering
      detection limits and extending the utility of GC-MS for steroid analysis. In this
      work, a Varian Saturn III GC-MS system has been used in its tandem mass
      spectrometry mode to detect low picogram levels of model steroids in standard
      solution and the urine matrix. Application of MS-MS-MS provided structurally
      informative spectra for 3'-hydroxystanozolol at concentrations of 1 ng/ml. In
      addition, four polysilphenylene-polydimethylsiloxane capillary columns were
      examined for background and selectivity. The columns had bleed several-fold lower
      than conventional polysiloxane columns. The columns also exhibited significant
      differences in selectivity for structurally similar steroids. Finally, a new
      temperature-programmed split-splitless injector was used to inject as much as 25
      microliters on column. The resulting limits of detection were 5 pg/ml for
      norandrosterone.

PMID- 9001951
TI  - Detection of testosterone misuse: comparison of two chromatographic sample
      preparation methods for gas chromatographic-combustion/isotope ratio mass
      spectrometric analysis.
AB  - Two chromatographic methods, reversed-phase liquid chromatography (LC) and
      immunoaffinity chromatography (IAC), were compared in the preparation of purified
      testosterone extracts suitable for gas chromatography-combustion/isotope ratio
      mass spectrometry (GC-C-IRMS) analysis. We have shown previously that GC-C-IRMS
      is a promising means of detection of testosterone misuse in sport. The two clean
      up procedures afford sufficient recovery and adequate purity of testosterone. LC
      presents several advantages over IAC: access to other urinary steroids, longer
      column life, no need for special equipment and no antibody preparation. For IAC,
      the antibodies to testosterone must be selected with care for high affinity and
      low cross-reactivity. Nevertheless, IAC is of some interest in our experiments,
      the recovery is slightly better for low concentrations of urinary testosterone
      and IAC does not induce isotopic discrimination even in overloading experiments.
      This is the first report on sample preparation by IAC prior to GC-C-IRMS and
      carbon isotope ratio values for urinary epitestosterone. The carbon isotope ratio
      test can identify users' urines missed by the testosterone to epitestosterone
      ratio (T/E > 6) test.

PMID- 9001955
TI  - Excretion study of furazabol, an anabolic steroid, in human urine.
AB  - Furazabol and 16-hydroxyfurazabol represented the most abundant peaks in urinary
      metabolic profiles for two men obtained by gas chromatography-mass spectrometry
      (GC-MS) after oral administration of 5 mg furazabol. The excreted amounts of
      unchanged furazabol were determined and its response in GC-MS was compared with
      that of the 16-hydroxy metabolite. The maximum excretion rates of these compounds
      were reached 2-3 h after oral administration. The half-lives of unchanged
      furazabol for two human subjects, were 1.87 and 1.29 h respectively and the
      recovered amount in 48 h was 24% (33% for one, 15% for the other). Also the
      spectrum of an unidentified metabolite is reported.

PMID- 9001956
TI  - Combined profile of androgen glucuro- and sulfoconjugates in post-competition
      urine of sportsmen: a simple screening procedure using gas chromatography-mass
      spectrometry.
AB  - An analytical screening procedure has been developed for the estimation of total
      androgen conjugates in post-competition urine, using gas chromatography-mass
      spectrometry with computerized data acquisition and concentration calculation.
      Rapid acid-catalyzed methanolysis is a key feature of the method, which allows
      simultaneous cleavage of glucuronides and sulfates. Analytical data generated by
      this method for testosterone and epitestosterone are in accordance with our
      previous results obtained by more accurate isotope dilution mass spectrometry.
      The usefulness of the ratio of testosterone glucuronide-total epitestosterone as
      an aid for a better discrimination between physiologically high and
      pharmacologically high ratios of testosterone glucuronide-epitestosterone
      glucuronide, which was demonstrated previously, has been confirmed here.

PMID- 9001957
TI  - Long-term detection and identification of metandienone and stanozolol abuse in
      athletes by gas chromatography-high-resolution mass spectrometry.
AB  - The misuse of anabolic androgenic steroids (AAS) in human sports is controlled by
      gas chromatography-mass spectrometric analysis of urine specimens obtained from
      athletes. The analysis is improved with modern high-resolution mass spectrometry
      (HRMS). The detection and identification of metabolites of stanozolol (I) [3'
      hydroxystanozolol (II) and 4 beta-hydroxystanozolol (III)] and metandienone (IV)
      I17 beta-methyl-5 beta-androst-1-ene-3 alpha,17 alpha-diol (V) and 18-nor-17,17
      dimethyl-5 beta-androsta-1,13-dien-3 alpha-ol (VI)] with GC-HRMS at 3000
      resolution yielded a large increase in the number of positive specimens. A total
      of 116 anabolic steroid positives were found in this laboratory in 1995 via GC-MS
      and GC-HRMS screening of 6700 human urine specimens collected at national and
      international sporting events and at out-of-competition testing. Of the 116
      positive cases, 41 were detected using conventional (quadrupole) GC-MS screening.
      The other 75 positives were identified via GC-HRMS screening. To confirm the HRMS
      screening result, the urine sample was reanalyzed using a specific sample workup
      procedure to selectively isolate the metabolites of the identified substance. II
      and III were selectively isolated via immunoaffinity chromatography (IAC) using
      an antibody which was prepared for methyltestosterone and shows high cross
      reactivity to II and III. V and VI were isolated using high-performance liquid
      chromatography (HPLC) fractionation.

PMID- 9001958
TI  - High doses of alcohol increase urinary testosterone-to-epitestosterone ratio in
      females.
AB  - The effect of alcohol (1.2 and 2.0 g/kg) on the urinary testosterone-to
      epitestosterone (T/E) ratio was studied by two experiments each conducted with
      four healthy females and males. The intake of 2.0 g/kg of ethanol within 5 h in
      the evening significantly increased plasma testosterone concentration and ratio
      of T/E in urine collected next morning in females. The results suggest that
      alcohol increases the T/E ratio more in females than in males. The effect of high
      doses of alcohol on urinary T/E ratio must be kept in mind when doping tests are
      performed during training periods.

PMID- 9001959
TI  - Profiling of urinary testosterone and luteinizing hormone in exercise-stressed
      male athletes, using gas chromatography-mass spectrometry and enzyme immunoassay
      techniques.
AB  - Knowledge of the effects of episodic or short-term exercise-stress on endogenous
      testosterone and luteinizing hormone levels still remains fragmentary and
      inconclusive. In this study, an approach based on the absolute concentrations of
      urinary total testosterone (T), luteinizing hormone (LH) and the T/LH
      concentration ratios, was used to profile short-term exercise-stress responses in
      healthy drug-free male athletes. Testosterone and luteinizing hormone
      concentrations were measured using gas chromatography-mass spectrometry (GC-MS)
      and microparticle enzyme immunoassay (MEIA) techniques, respectively. Stress
      profiles derived from exercise-stress at VO2max, 68.1% VO2max and 51.6% VO2max
      were plotted using the concentrations of T, LH and the ratios of T/LH found under
      non-stressed and stressed conditions. Significant changes in LH concentrations (p
      < 0.005) and T/LH ratios (p < 0.005) levels were observed between the pre-stress
      and post-exercise conditions during acute exercise-stress at VO2max but the T
      concentration did not show any marked change relative to the non-stressed
      condition. Whilst exercise-stress appeared to reduce the change in T
      concentrations between the pre- and post-exercise states compared to that in the
      non-stressed control condition, the change in LH concentrations showed a moderate
      increase at submaximal oxygen uptake values. The stress profiles derived from
      this study facilitated an assessment of the relationship between the endogenous
      T, LH and T/LH ratio stress-responses over a short period of applied exercise
      stress.

PMID- 9001960
TI  - Detection of diuretic agents in doping control.
AB  - Since the inclusion of diuretics in the list of banned substances in sports in
      1988, a large number of screening and confirmation procedures to detect the
      presence of these substances in urine samples have been developed. In this paper,
      a review of the analytical methodology described to analyze diuretics is
      presented. The paper has been focused on the needs of doping control and mainly
      screening procedures including sample preparation and liquid or gas
      chromatographic separation have been considered. More relevant papers using
      capillary zone electrophoresis have been also considered. Mass spectrometry is
      mandatory in doping control for confirmation purposes, and finally, mass
      spectrometric techniques described for diuretics have been reviewed.

PMID- 9001961
TI  - Direct determination of diuretic drugs in urine by capillary zone electrophoresis
      using fluorescence detection.
AB  - Four diuretic drugs banned in sport (amiloride, triamterene, bendroflumethiazide
      and bumetanide) have been separated by capillary zone electrophoresis (CZE) and
      detected using conventional fluorescence spectrometry. The effect of pH on
      electrophoretic parameters such as migration time, peak efficiency and peak
      height is discussed. Complete separation of the four drugs is achieved in less
      than 8 min at pH 8. No interference due to endogenous urine components is
      observed and thus direct urine analysis is feasible. Analytical figures of merit
      including precision and limits of detection are presented. Limits of detection
      range between 0.5 fmol for triamterene and 21.6 fmol for bumetanide.

PMID- 9001962
TI  - Quantitative structure-retention relationships in doping control.
AB  - Regression equation modelling was used for the correlation of gas chromatographic
      relative retention times tRR of anabolic steroids, stimulants and narcotics with
      their molecular characteristics in order to create a model for the prediction of
      tRR values of unanalyzed molecules. Predicting chromatographic retention
      parameters is one of the main goals of the quantitative structure-retention
      relationships (QSRR) methodology. To be performed, QSRR studies require two
      tools; a methodology for the extraction of the structural characteristics and a
      statistical program for the correlation of these characteristics with the
      chromatographic data.

PMID- 9001963
TI  - Transmission of the results of tests for International Olympic Committee-defined
      drugs of abuse.
AB  - The hardware and software facilities for electronic storage, transfer and
      handling of data is such that multipurpose databases can be made accessible
      without geographic restriction at low cost. The versatile and flexible underlying
      structures allow for ease of access and retrieval of data and gives presentation
      formats fully comparable to printed counterparts. Because of the apparent ease of
      use and because of the wider distribution of the information, misinterpretation
      is more likely to occur than in oral or written presentation for more restricted
      and more culturally homogeneous audiences. This necessitates some degree of
      harmonisation/standardisation of data on transfer, while allowing local
      expression forms at sender and receiver ends (Fig. 1). This document is part of
      an ongoing international effort to agree on some sort of "standardisation" of the
      transmission and presentation of "laboratory results". It centers on the domain
      of drugs of abuse as defined by the International Olympic Committee.

PMID- 9001964
TI  - Automated analysis of drugs in urine.
AB  - A totally automated procedure has been developed for the preparation and analysis
      of 34 basic and neutral drugs in urine samples using an integrated HP 7686
      PrepStation-HP 6890 gas chromatographic system. The automated preparation of the
      sample consisted of a liquid-liquid extraction of 250 microliters urine at
      alkaline pH with 100 microliters of methyl tert.-butyl ether. After phase
      separation the organic solvent was automatically placed in the injector of the
      gas chromatograph and analysed. High recoveries of extraction were obtained. The
      limits of detection of most of the drugs were less than 0.5 microgram/ml. The
      method, which allows the preparation and analysis of the samples to be completely
      synchronised, showed good accuracy and precision.

PMID- 9001965
TI  - Erythropoietin: physico- and biochemical analysis.
AB  - A hormone, erythropoietin, mainly produced in adult kidneys and fetal livers,
      acts on bone marrow erythroid progenitor cells to regulate the production of
      erythrocyte in mammals. As a result, the oxygen carrying capacity of blood
      increases and the increased oxygen supply raises the cardiac function and
      physiological working capacity. Erythropoietin is possibly misused by athletes in
      sports for the purpose of improving performance. Presently there is no
      discernible and specific method to identify erythropoietin administration for
      doping control. To address this practical problem, this paper presents a summary
      of the applications of analytical biotechnology, especially the structural
      characterization of erythropoietin.

PMID- 9001966
TI  - Detection of human growth hormone doping in urine: out of competition tests are
      necessary.
AB  - The misuse of human growth hormone (hGH) in sport is deemed to be unethical and
      dangerous because of various adverse effects. Thus, it has been added to the
      International Olympic Committee list of banned substances. Until now, the very
      low concentration of hGH in the urine made its measurement difficult using
      classical methodology. Indeed, for routine diagnosis, only plasma measurements
      were available. However, unlike blood samples, urine is generally provided in
      abundant quantities and is, at present, the only body fluid allowed to be
      analysed in sport doping controls. A recently developed enzyme-linked
      immunosorbent assay (Norditest) makes it now possible, without any extraction, to
      measure urinary hGH (u-hGH) in a dynamic range of 2-50 ng hGH/l. In our protocol,
      untreated and treated non-athlete volunteers were followed. Some of them received
      therapeutical doses of recombinant hGH (Norditropin) for one week either
      intramuscularly (three increasing doses) or subcutaneously (12 i.u. every day).
      The u-hGH excretion after treatment showed dramatic increases of 50-100 times the
      basal values and returned to almost the mean normal level after 24 h. u-hGH was
      also measured in samples provided by the anti-doping controls at major and minor
      competitions. Depending on the type of efforts made during the competition, the
      hGH concentration in urine was dramatically increased. Insulin-like growth factor
      binding proteins and beta 2-microglobulins in urine and/or in blood could be
      necessary for the correct investigation of any hGH doping test procedure.

PMID- 9001967
TI  - Immunoaffinity trapping of urinary human chorionic gonadotropin and its high
      performance liquid chromatographic-mass spectrometric confirmation.
AB  - A method has been developed for confirmation of the glycopeptide human chorionic
      gonadotropin (hCG) in urine. A solid-phase immunoaffinity trapping technique
      utilizing a monoclonal antibody recognizing both intact hCG and free hCG beta
      subunits was developed for the extraction of hCG from urine. Recovery of hCG from
      a urine matrix was essentially quantitative. The hCG was quantitatively eluted
      with 6 M guanidine hydrochloride, reductively alkylated with vinylpyridine, and
      subjected to tryptic digestion. The tryptic digest was analyzed by HPLC-MS. Ions
      from three tryptic fragments were monitored with selected ion monitoring to
      provide specific detection of hCG. The signal observed for a concentration of 25
      mIU/ml of hCG could be clearly distinguished from background with a signal-to
      noise ratio of 12:1.

PMID- 9001968
TI  - Stimulants, narcotics and beta-blockers: 25 years of development in analytical
      techniques for doping control.
AB  - More than 25 years of developing doping control methods have led to comprehensive
      screening and confirmation procedures for stimulants, narcotics and beta
      blockers. Much of this work has been initiated and/or improved by the late Prof.
      Dr. Manfred Donike. The methodological approach covered in this overview was
      applied to doping control procedures during the XXV Summer Olympics in Barcelona,
      Spain, in 1992 and the XVII Winter Olympics in Lillehammer, Norway, in 1994.
      Urine samples are screened through a combination of two analytical methods that
      are complementary: (a) gas chromatographic analysis of the parent compound and
      unconjugated metabolites, following single-step sample extraction and detection
      by a nitrogen-specific detector based on a retention index identification system
      and (b) gas chromatographic analysis including also conjugated drugs and
      metabolites after hydrolysis, solid-phase extraction, derivatisation and mass
      spectrometric detection. Confirmation and identification is always performed by
      gas chromatographic separation and full scan mass spectrometric detection. These
      methods facilitate the rapid screening and confirmation of more than 100
      stimulants, narcotic analgesics and beta-blockers in urine for at least 24 h
      after the intake of a pharmaceutical dose. Application of the methods ensures
      high quality standards for the unequivocal identification of doping agents as
      well as a rapid turnaround time for sample analyses.

PMID- 9001969
TI  - Amphetamine and methamphetamine determination in urine by reversed-phase high
      performance liquid chromatography with simultaneous sample clean-up and
      derivatization with 1,2-naphthoquinone 4-sulphonate on solid-phase cartridges.
AB  - A liquid-solid procedure is proposed for sample clean-up and derivatization of
      amphetamine and methamphetamine in urine samples. The reagent was 1,2
      naphthoquinone 4-sulphonate, and a commercial C18 packing cartridge was used. The
      samples derivatized at room temperature were chromatographed on a 5-microns
      Hypersil ODS (250 x 4 mm I.D.) with an elution gradient of acetonitrile-water
      containing propylamine. Under these conditions, the amines were eluted with short
      retention times. The procedure was used to determine amphetamine, or
      methamphetamine with its metabolite amphetamine, in spiked urine samples. The
      detection limit (at a signal-to-noise ratio of 3) for amphetamine (0.1
      microgram/ml) was similar to that obtained with liquid-liquid derivatization and
      to those obtained with immobilized reagents on a polymeric solid support. The
      detection limit for methamphetamine (0.4 microgram/ml) was higher than with the
      liquid-liquid procedure because of the lower reactivity on the cartridge. The
      precision and accuracy of the method were also studied.

PMID- 9001970
TI  - Threshold level for theophylline in doping analysis.
AB  - HPLC in the reversed-phase mode is used to assay methylxanthines including
      theobromine, paraxanthine, theophylline and caffeine in urine. The calibration
      graphs show good linearity in the concentration range 0-10 micrograms/ml. The
      limit for accurate quantitation of theophylline was 0.25 microgram/ml. Between 6
      and 20% of the parent drug is recovered in urine (0-12 h) after the oral
      administration of sustained release preparations containing 150 and 250 mg
      theophylline to four volunteers. Theophylline levels above 0.25 microgram/ml were
      found in 1539 out of 3885 urine samples collected from athletes during
      unannounced doping control in Flanders. Statistical evaluation of the results
      gives a far outside value [75th percentile+(3 x interquartile range)] of 2.25
      micrograms/ml. The ratio theophylline paraxanthine (TP/PX) as an indicator for
      the non-dietary intake of theophylline seems to be more reliable. The far outside
      ratio was 0.20. To ensure with the greatest possible degree of certainty that no
      false-positive result is reported, decision limits of 5 micrograms/ml and 0.50,
      for theophylline and the ratio TP/PX respectively, are proposed.

PMID- 9001971
TI  - Identification of a pyrovalerone metabolite in the rat by gas chromatography-mass
      spectrometry and determination of pyrovalerone by gas chromatography-nitrogen
      phosphorus detection.
AB  - Pyrovalerone and its hydroxylated metabolite have been identified by gas
      chromatography-mass spectrometry in rat urine and plasma. A sensitive gas
      chromatographic method for the quantitative analysis of pyrovalerone in rat urine
      and plasma is described. The method also permits the quantitative monitoring of
      the urinary excretion of the drug and its metabolite. Pyrovalerone and its
      hydroxylated metabolite are detected up to 18 h after a single oral
      administration to the rat at a dose of 20 mg/kg.

PMID- 9001972
TI  - Analysis of mesocarb analogues in urine and plasma of rats by high-performance
      liquid chromatography and thermospray liquid chromatography-mass spectrometry.
AB  - The pharmacokinetics and metabolism of synthetic 2-hydroxymesocarb and 4-methyl-2
      hydroxymesocarb analyzed by HPLC-DAD and thermospray LC-MS were studied in rats.
      Multistep liquid-liquid extraction (LLE) was used with diethyl ether at pH 7.0.
      The major metabolites of 2-hydroxymesocarb in both urine and plasma of the rat
      were the p-hydroxylated derivative of the phenylcarbamoyl group of the parent
      drug. The metabolites of 4-methyl-2-hydroxymesocarb in urine of rats may be the
      oxidized forms at the phenylcarbamoyl group of the parent drug. Absorption (ka)
      and elimination (ke) rate constants in plasma of 2-hydroxy-mesocarb were 0.0300
      and 0.00485 min-1, respectively; those of 4-methyl-2-hydroxymesocarb were 0.0546
      and 0.00797 min-1, respectively. The half-lives (t1/2) of 2-hydroxymesocarb and 4
      methyl-2-hydroxymesocarb in plasma were 144 and 86 min, respectively.

PMID- 9001973
TI  - Point process models of single-neuron discharges.
AB  - In most neural systems, neurons communicate via sequences of action potentials.
      Contemporary models assume that the action potentials' times of occurrence rather
      than their waveforms convey information. The mathematical tool for describing
      sequences of events occurring in time and/or space is the theory of point
      processes. Using this theory, we show that neural discharge patterns convey time
      varying information intermingled with the neuron's response characteristics. We
      review the basic techniques for analyzing single-neuron discharge patterns and
      describe what they reveal about the underlying point process model. By applying
      information theory and estimation theory to point processes, we describe the
      fundamental limits on how well information can be represented by and extracted
      from neural discharges. We illustrate applying these results by considering
      recordings from the lower auditory pathway.

PMID- 9001974
TI  - On the analytic solution of electrotonic spread in branched passive dendritic
      trees.
AB  - From the classical work of Rall it is known that the spread of electric potential
      in a passive dendritic tree may be obtained by expressing the initial conditions
      as a linear combination of a set of trigonometric eigenfunctions, each decaying
      with the associated time constant. It is shown here that in order to evaluate the
      permissible parameters in these eigenfunctions one may formulate the boundary
      conditions at all the junctions and endings of the dendritic tree as a set of
      homogeneous linear equations in which the parameters in the eigenfunctions are
      the unknowns. These equations have a nontrivial solution if the relevant
      determinant vanishes, a condition that permits the evaluation of the various
      parameters, thus providing an analytic approach to the expression of the
      eigenfunctions as well as the decay time constants. The above approach is
      illustrated by application to a dendritic tree that has a parent segments and two
      generations of offspring segments, without any restrictions as to the relative
      diameters or lengths of the various segments in the tree. General properties of
      the tree may be readily derived, like the variation of the eigenvalues on scaling
      of the lengths or diameters of all the segments. A few special cases with
      specified dimensions of the various segments are derived from the general case.
      In the case of a dendritic tree that fulfills the "equivalent cylinder"
      conditions, all of the eigenvalues and eigenfunctions of the tree may be
      determined by the proposed method, including those that do not apply to the
      equivalent cylinder. The orthogonality properties of the eigenfunctions are
      discussed.

PMID- 9001976
TI  - Modeling of the H-reflex facilitation during ramp and hold contractions.
AB  - Healthy subjects were asked to make a voluntary ramp and hold contraction. The
      duration of the ramp stage was 500 ms, and the torque increment in this period
      was set to 15 Nm. The contraction was made from a relaxed and from a 5 Nm
      background torque situation. Hoffmann (H-) reflexes were elicited during the
      voluntary contraction, mostly with 100 ms intervals. These experiments showed an
      increase (facilitation) in the H-reflex before the torque or the EMG started to
      increase. This facilitation of the H-reflex remained during all the stages of the
      voluntary movement and declined to normal levels again only at the very end of
      the hold phase, which lasted for one second. This specific pattern of
      facilitation during a voluntary contraction was modeled using a modeling
      language, that is specifically designed to calculate neuronal systems with a high
      degree of reality (Ekeberg et al., 1991). Our model consisted of a motoneuron
      pool with 200 neurons connected to an EMG-model of the human soleus muscle and an
      extra group of higher-level neurons for controlling the amount of decrease of
      presynaptic inhibition. The model was used to simulate the observed modulation of
      the H-reflex with both a presynaptic and a postsynaptic mechanism. Simulations
      showed that a continuous change in the descending control signals is needed to
      make the model based on postsynaptic mechanism fit with the experimental data,
      whereas no extra control from the CNS over the excitatory drive to the motoneuron
      pool is needed when the decrease of presynaptic inhibition mechanism is applied.

PMID- 9001975
TI  - The intrinsic electrophysiological characteristics of fly lobula plate tangential
      cells: I. Passive membrane properties.
AB  - The passive membrane properties of the tangential cells in the fly lobula plate
      (CH, HS, and VS cells, Fig. 1) were determined by combining compartmental
      modeling and current injection experiments. As a prerequisite, we built a digital
      base of the cells by 3D-reconstructing individual tangential cells from cobalt
      stained material including both CH cells (VCH and DCH cells), all three HS cells
      (HSN, HSE, and HSS cells) and most members of the VS cell family (Figs. 2, 3). In
      a first series of experiments, hyperpolarizing and depolarizing currents were
      injected to determine steady-state I-V curves (Fig. 4). At potentials more
      negative than resting, a linear relationship holds, whereas at potentials more
      positive than resting, an outward rectification is observed. Therefore, in all
      subsequent experiments, when a sinusoidal current of variable frequency was
      injected, a negative DC current was superimposed to keep the neurons in a
      hyperpolarized state. The resulting amplitude and phase spectra revealed an
      average steady-state input resistance of 4 to 5 M omega and a cut-off frequency
      between 40 and 80 Hz (Fig. 5). To determine the passive membrane parameters Rm
      (specific membrane resistance), Ri (specific internal resistivity), and Cm
      (specific membrane capacitance), the experiments were repeated in computer
      simulations on compartmental models of the cells (Fig. 6). Good fits between
      experimental and simulation data were obtained for the following values: Rm = 2.5
      k omega cm2, Ri = 60 omega cm, and Cm = 1.5 microF/cm2 for CH cells; Rm = 2.0 k
      omega cm2, Ri = 40 omega cm, and Cm = 0.9 microF/cm2 for HS cells; Rm = 2.0 k
      omega cm2, Ri = 40 omega cm, and Cm = 0.8 microF/cm2 for VS cells. An error
      analysis of the fitting procedure revealed an area of confidence in the Rm-Ri
      plane within which the Rm-Ri value pairs are still compatible with the
      experimental data given the statistical fluctuations inherent in the experiments
      (Figs. 7, 8). We also investigated whether there exist characteristic differences
      between different members of the same cell class and how much the exact placement
      of the electrode (within +/-100 microns along the axon) influences the result of
      the simulation (Fig. 9). The membrane parameters were further examined by
      injection of a hyperpolarizing current pulse (Fig. 10). The resulting
      compartmental models (Fig. 11) based on the passive membrane parameters
      determined in this way form the basis of forthcoming studies on dendritic
      integration and signal propagation in the fly tangential cells (Haag et al.,
      1997; Haag and Borst, 1997).

PMID- 9001978
TI  - Prognostic evaluation of specific cutaneous infiltrates in B-chronic lymphocytic
      leukemia.
AB  - The relationship between numerous histologic variables and survival was
      investigated in 54 consecutive lesions of specific skin infiltrates of B-cell
      chronic lymphocytic leukemia (B-CLL) from 27 patients (16 males and 11 females,
      mean age 65 years, range 42-83 years). All patients were followed for up to 204
      months or until death. Histopathologically, the infiltrates showed a patchy
      perivascular (35%), diffuse (31.5%), nodular (31.5%) or bandlike (1.9%) pattern.
      In 28% of the cases, an admixture of reactive cells within the infiltrate
      including eosinophils, histiocytes, neutrophils and plasma cells was observed.
      Cytomorphologically, small B-lymphocytes with condensed chromatin predominated in
      most infiltrates. However, some biopsies showed a small but significant number of
      medium- or large-sized neoplastic cells of the B-lymphocyte lineage with variable
      cytomorphological features. In a multivariate analysis, several histologic
      parameters within the infiltrates were found to show a significant association
      with long survival, namely, an infiltrate of moderate density, a nodular pattern,
      involvement of the lower dermis only, and presence of predominantly small B
      lymphocytes (more than 95%) with condensed chromatin. Histologic variables that
      independently correlated with relatively short survival included an infiltrate of
      severe intensity, a diffuse pattern, epidermal changes (especially acanthosis and
      ulceration), medium-sized and large B-lymphocyte (more than 5%), and reactive
      cells within the infiltrate (neutrophils, eosinophils, and plasma cells). Overall
      analysis of our results showed two histologic patterns with a significant
      prognostic impact (p < 0.01; z = 5.4). Pattern I (33 biopsies) correlated with
      relatively long survival (2-year survival rate; 97%) and consisted of infiltrates
      showing predominantly small B-lymphocytes (more than 95%) without reactive cells
      or epidermal changes. Pattern II (21 biopsies) indicated short survival (2-year
      survival rate; 49%) and included all the rest of the biopsies i.e., infiltrates
      with medium- and large-sized B-lymphocytes (more than 5%), admixture of reactive
      cells, and epidermal changes. Results from our study suggest that histologic
      features in specific skin infiltrates of B-chronic lymphocytic leukemia may be
      helpful in identifying prognostically different subgroups of patients and
      planning therapeutic schedules.

PMID- 9001977
TI  - The use of system identification techniques in the analysis of oculomotor burst
      neuron spike train dynamics.
AB  - The objective of system identification methods is to construct a mathematical
      model of a dynamical system in order to describe adequately the input-output
      relationship observed in that system. Over the past several decades, mathematical
      models have been employed frequently in the oculomotor field, and their use has
      contributed greatly to our understanding of how information flows through the
      implicated brain regions. However, the existing analyses of oculomotor neural
      discharges have not taken advantage of the power of optimization algorithms that
      have been developed for system identification purposes. In this article, we
      employ these techniques to specifically investigate the "burst generator" in the
      brainstem that drives saccadic eye movements. The discharge characteristics of a
      specific class of neurons, inhibitory burst neurons (IBNs) that project
      monosynaptically to ocular motoneurons, are examined. The discharges of IBNs are
      analyzed using different linear and nonlinear equations that express a neuron's
      firing frequency and history (i.e., the derivative of frequency), in terms of
      quantities that describe a saccade trajectory, such as eye position, velocity,
      and acceleration. The variance accounted for by each equation can be compared to
      choose the optimal model. The methods we present allow optimization across
      multiple saccade trajectories simultaneously. We are able to investigate
      objectively how well a specific equation predicts a neuron's discharge pattern as
      well as whether increasing the complexity of a model is justifiable. In addition,
      we demonstrate that these techniques can be used both to provide an objective
      estimate of a neuron's dynamic latency and to test whether a neuron's initial
      firing rate (expressed as an initial condition) is a function of a quantity
      describing a saccade trajectory (such as initial eye position).

PMID- 9001979
TI  - Expression of the mast cell growth factor interleukin-3 in melanocytic lesions
      correlates with an increased number of mast cells in the perilesional stroma:
      implications for melanoma progression.
AB  - The molecular events responsible for tumor progression in human cutaneous
      malignant melanoma remain unclear; however, critical to the process is the
      dysregulated proliferation of tumor cells and the development of new vascular
      channels which allow further growth and dissemination. Connective tissue mast
      cells (MC) have been implicated in tumor progression because they concentrate
      around tumors (including melanomas) prior to the formation of new blood vessels,
      and because they contain many chemical mediators, including basic fibroblast
      growth factor (bFGF), known to have mitogenic and angiogenic effects. Several MC
      chemotactic and mitogenic factors have been described including interleukin-3 (IL
      3). In order to determine whether there is a differential expression of this MC
      chemotactic/mitogenic factor with tumor progression in vivo, we evaluated by
      immunohistochemistry 85 melanocytic lesions including primary invasive malignant
      melanoma (PIMM), melanoma in situ (MMIS), and ordinary intradermal benign
      melanocytic nevi (BMN) for expression of IL-3. Nucleic acid in situ hybridization
      also was used to evaluate the melanocytic lesions for IL-3-specific mRNA
      transcripts. Intracellular IL-3 protein was detected in 29/33 (88%) PIMM and
      15/25 (60%) MMIS, but was not detected in any (0/27; 0%) BMN (p < 0.0001). IL-3
      specific mRNA transcripts were present in 3/4 PIMM and 2/10 MMIS in which IL-3
      protein was not identified, but were not detected in any BMN. IL-3 mRNA or
      protein was not detected in normal melanocytes present in the perilesional
      epidermis of any of the specimens studied. Immunohistochemistry also was used to
      confirm the presence of IL-3 alpha-specific receptors on human cutaneous MC. As
      demonstrated by others, a significantly increased number of MC was present in the
      perilesional stroma of PIMM and MMIS vis a vis BMN (p < 0.0001). The results
      suggest that melanoma cells may attract MC in vivo by producing MC
      chemotactic/mitogenic factors such as IL-3. The recruitment of MC and the
      subsequent release of their potent mitogenic and angiogenic factors such as bFGF
      may thus represent a tumor-host interaction which favors tumor progression. Reed
      JA, McNutt NS, Bogdany JK, Albino AP. Expression of the mast cell growth factor
      interleukin-3 in melanocytic lesions correlates with an increased number of mast
      cells in the perilesional stroma: implications for melanoma progression.

PMID- 9001980
TI  - The prognostic significance of basic fibroblast growth factor in cutaneous
      malignant melanoma.
AB  - Basic fibroblast growth factor (bFGF) is a growth factor and an angiogenesis
      factor which may play a role in the evolution of cutaneous malignant melanoma
      (CMM). In this study, we evaluated the distribution of bFGF in CMM using
      immunochemical methods and correlated the pattern of bFGF expression with the
      clinical course. Formalin-fixed, paraffin-embedded sections of 46 CMMs were
      immunostained with a high-affinity purified antibody raised against human bFGF.
      CMM were categorized into lesions that exhibited subsequent recurrence (local,
      regional and/or systemic) or recurrence-free lesions. The minimum follow-up time
      was 5 years. Expression of bFGF within the tumors and in peritumoral and
      intratumoral blood vessels was similar in the two groups. Comparable results were
      attained when 8 recurring vs 8 non-recurring CMM, selected from the above tumors,
      were matched for age, gender, anatomic site and tumor thickness. These results
      suggest that the biologic behavior of CMM may not be predicted by
      immunoreactivity to bFGF in CMM cells or in the local tumor vasculature.

PMID- 9001981
TI  - Curvicircular intracytoplasmic membranous structures in keratinocytes of
      pemphigus foliaceus.
AB  - We noticed intracytoplasmic membranous, annular, or circular structures in the
      lesion of pemphigus foliaceus and studied these by regular transmission electron
      microscopy and immunoelectron microscopy. These curvicircular bodies were
      observed in the preacantholytic keratinocytes of the blister wall as well as in
      acantholytic cells in 6 out of 6 patients with pemphigus foliaceus. They were
      absent in samples from 3 patients with pemphigus vulgaris. These structures were
      about 60-70 nm wide and consisted of 4 electron-dense layers. They were
      continuous with intact desmosomal structures and gap junctions in the periphery
      of the keratinocytes. These curvicircular membranous bodies were well labeled
      with immunogold particles for desmoglein, plakoglobin, connexin 43, and IgG. In
      contrast to pemphigus vulgaris, splitting of desmosomes through dissolution of
      intercellular desmoglea was seldom observed in all 6 specimens of pemphigus
      foliaceus. These findings suggest that in pemphigus foliaceus 1) curvicircular
      bodies are derived from internalized desmosomes and gap junctions, and 2) cell-to
      cell adhesions are weakened by this internalization and acantholysis is
      initiated, while in pemphigus vulgaris the dissolution of desmoglea is the
      initial event. It is suggested that in pemphigus foliaceus the binding of
      autoantibody induces internalization of many intact desmosomes and gap junctions
      rather than splitting them.

PMID- 9001982
TI  - Ultrastructural localization of carcinoembryonic antigen (CEA) glycoproteins and
      epithelial membrane antigen (EMA) in normal and neoplastic sweat glands.
AB  - Glycoproteins of the carcinoembryonic antigen family (CEA) and epithelial
      membrane antigen (EMA) are established markers for glandular and mucosal tissues.
      However, their precise ultrastructural distribution in sweat glands has not been
      determined as yet. Therefore, normal human skin, 19 cases of various sweat gland
      neoplasms, Paget's disease, and cutaneous metastases of visceral carcinomas were
      stained with well-defined antibodies using a postembedding immunogold technique.
      In some cases, a new method of re-embedding paraffin material for immunoelectron
      microscopy was applied. In normal sweat glands, immunoreactivity of the
      endoplasmic reticulum and vesicles indicated biosynthesis and processing of CEA
      and EMA. Along the luminal surfaces both CEA and EMA represented an integral part
      of microvilli. However, a differential expression of CEA and EMA was demonstrated
      in apocrine epithelia, mucous cells of eccrine glands, and sweat ducts. In fetal
      glands, CEA was associated with formation of secretory and ductal lumina. The
      overall cellular distribution of CEA and EMA was highly preserved in benign sweat
      gland neoplasms whereas malignant neoplasms were characterized by loss of protein
      targeting and cellular polarity. In conclusion, these immunoelectron
      microscopical findings suggest a role of CEA and EMA for cell differentiation and
      secretory mechanisms of sweat gland epithelia.

PMID- 9001983
TI  - Chondroid syringoma: an immunohistochemical study using antibodies to Ca 15-3, KA
      93, Ca 19-9, CD44 and BM-1.
AB  - The expression of Ca 15-3, KA-93, Ca 19-9, CD44 and BM-1 in normal skin and
      chondroid syringoma was investigated immunohistochemically using antibodies to
      these antigens. In the normal skin, the eccrine ducts and/or secretory elements
      were positive for all these antigens. On the other hand, the apocrine ducts
      and/or secretory elements were positive for the antibodies to Ca 15-3, KA-93 and
      CD44. In chondroid syringoma, the luminal cells of tubuloglandular structures
      were positive for the antibodies to Ca 15-3 and BM-1, and partly positive for
      those to KA-93 and Ca 19-9. The basal cells of the tubular structures and solid
      nests were positive only for the antibody to CD44. Stromal cells in the myxoid
      area were positive for the antibodies to KA-93 and CD44, and the chondroid matrix
      was positive for the antibody to BM-1. It is suggested that chondroid syringoma
      might originate from, or differentiate into the ducts and/or secretory elements
      of the eccrine sweat glands. In addition, the significance of the expression of
      BM-1 in the chondroid matrix is discussed.

PMID- 9001984
TI  - Mitotic granuloma annulare: a clinicopathologic study of 20 cases.
AB  - The finding of mitotic figures in granuloma annulare (GA) has not been emphasized
      in the literature. We describe 20 cases of a cellular, mitotically active variant
      of GA; we defined this group as cases having > or = 1 mitosis per 10 hpf.
      Clinically, the lesions could not be distinguished from typical, localized GA:
      there were 9 males and 11 females with a mean patient age of 49 +/- 15 years
      (mean +/- SD), compared to 45 +/- 20 years in a randomly selected control group
      of 60 patients with GA, and no unusual sites of predilection were noted.
      Histologically, a classic, palisading granuloma pattern predominated (18/20
      cases). Lesions were located in the mid-dermis and tended to be more cellular
      than typical GA. The histiocytes comprising the lesion often had enlarged nuclei
      and prominent nucleoli. The number of mitoses per 10 hpf was 3.0 +/- 1.5 (range
      1.0-7.2), control group 0.3 +/- 0.5; occasional atypical mitotic figures were
      observed. The proliferative nature of these lesions was confirmed using MIB-1
      staining; the percentage of MIB-1 positive cells ranged from 5%-29% (mean 15 +/-
      6%). Mitotic GA must be distinguished histologically from neoplastic processes,
      in particular epithelioid sarcoma. We conclude that histiocytes in clinically
      typical GA can exhibit an increased mitotic rate. Recognition of this variant is
      important in order to avoid overdiagnosis of a malignant condition.

PMID- 9001985
TI  - Spindle cell lipoma is strongly CD34 positive. An immunohistochemical study.
AB  - Spindle cell lipoma (SCL) is an uncommon soft tissue neoplasm that may provide
      diagnostic difficulty to the histopathologist. Four retrospectively identified
      SCLs were evaluated immunohistochemically with a broad panel of antibodies (CD34,
      factor XIIIa, S-100, actin and factor VIII). All four SCLs were strongly CD34
      positive (95 to 100% of cells) and focally factor XIIIa positive (average 16% of
      cells). Tumor cells were S-100, actin and factor VIII negative.
      Dermatofibrosarcoma protuberans, neurofibroma, schwannoma and angiolipoma are
      CD34 positive tumors that have some similar histologic features to SCL and may be
      considered in the differential diagnosis. Differentiation is possible using a
      broad panel of immunostains and routine diagnostic criteria.

PMID- 9001986
TI  - Myxoid dermatofibrohistiocytoma: an indolent post-traumatic tumor composed of
      CD34+ epithelioid and dendritic cells and factor XIIIa+ dendrophages.
AB  - Factor XIIIa+ dendrophages and CD34+ "deep dermal dendrocytes" are distinct
      subsets of embryonic dermal dendritic stem cells that persist in interstitial and
      adventitial sites in adult dermis. We encountered a unique myxoid dermal tumor
      composed of these two cell types. It arose after trauma to the thumb of a 49-year
      old man and was locally excised. The patient is without recurrence at 18 months.
      The disc-shaped tumor was lobulated, yellow, and mucoid and involved the margins.
      A fibrillar myxoid stroma contained mast cells, wispy collagen with medium-to
      small vessels, and loosely deployed small eosinophilic tumor cells. The tumor
      cells were amitotic and had oval or bean-shaped, bland nuclei; some cells were
      binucleated. The cells were epithelioid or dendritic with bipolar, stellate, and
      racquet-shaped cytosomes whose tapering cell processes blended with fibrillar
      collagen. Vacuolated epithelioid cells focally formed vessel-like luminal
      structure. All cells strongly expressed vimentin. Thirty percent of the tumor
      cells were elongated, dendritic factor XIIIa+ cells whose dendritic processes
      enshrouded mast cells or FXIIIa-negative tumor cells. A subset of the FXIIIa+
      cells also expressed MAC387 and lysozyme. The other 70% of the cells were CD34+.
      Many CD34+ cells were epithelioid with strong membrane and vacuolar decoration.
      Some CD34+ epithelioid cells had globular cytoplasmic inclusions. Other CD34+
      cells were dendritic with multipolar fibrobroblast-like cytosomes and weaker
      CD34+ membrane decoration. Actin and S-100 were negative. Ki 67 was expressed in
      1% of the tumor cells. Double stains for CD34 and Ki 67 showed that both CD34+
      cells and FXIIIa+ dendrophages were Ki 67+, as were many papillary dermal vessel
      endothelial cells. The composition of the tumor by mast cells, FXIIIa+
      dendrophages, and CD34+ primitive cells recapitulates the dermal microvascular
      unit. We propose the descriptive term myxoid dermatofibrohistiocytoma (MD) for
      this novel tumor. It appears to be an unusual response by dermal dendritic cells,
      perhaps due to continued stimulation by post-traumatic cytokines. Clarification
      of its biology and nosology awaits identification and study of more cases.

PMID- 9001987
TI  - Ossifying epithelioid hemangioendothelioma.
AB  - A case of small epithelioid hemangioendothelioma encapsulated by an egg-shaped
      bony shell composed of newly formed mature lamellar bone is presented. A nodule
      measuring 10 x 5 x 5 mm was excised from inside of the right cheek muscle of a 46
      year-old man. Histopathologically, the nodule consisted mainly of round-to-short
      spindled epithelioid cells with round nuclei and occasional cytoplasmic vacuoles
      associated with some foci of osseous metaplasia. Characteristically, egg shell
      like lamellar bone enclosed this lesion showing well-circumscribed appearance.
      The main component cells were immunohistochemically stained positive for factor
      VIII-related antigen, CD 34, UEA-1, and vimentin, and proved to be vascular
      endothelial cells. The term ossifying epithelioid hemangioendothelioma is
      proposed for this unique lesion. This type of epithelioid hemangioendothelioma
      has not been previously reported to our knowledge, and differentiation from
      ossifying fibromyxoid tumor of soft parts is considered to be important.

PMID- 9001988
TI  - Dermatofibroma with granular cells.
AB  - A new histologic variant of dermatofibroma, only briefly alluded to in
      dermatological literature is reported. This tumor was located in the back of a 24
      year-old man. It was present for about 2 years and had a history of trauma 2
      months before excision. The lesion showed similar characteristics to those of
      conventional dermatofibroma as well as the presence of groups of granular cells
      identical to those seen in granular cell tumors. It is important to recognize
      dermatofibroma with granular cells because it may be confused with a variety of
      benign or malignant soft tissue tumors containing similar granular cells that
      entail different significance or prognosis. The immunohistochemical study
      supports a granular cell change in a dermatofibroma instead of a granular cell
      tumor that has been traumatized, with secondary formation of a dermatofibroma
      reaction.

PMID- 9001989
TI  - Malignant eccrine poroma with multiple visceral metastases: report of a case with
      autopsy findings.
AB  - An autopsy case of malignant eccrine poroma (MEP) with multiple visceral
      metastases is reported. A flat, dark tumor of 1 cm in diameter developed on a pre
      existing pigmented spot at the left side of the waist of a 58-year-old male. The
      histopathology suggested the tumor to be malignant melanoma. Nine years later, a
      painless swelling occurred in the left lower leg, resulting from the obstruction
      of lymphatics at the left inguinal region. The swelling continued and spread with
      pain, reaching the inguinal region. Two years later, several papules appeared
      around the left knee, from which an extensive lymphorrhea occurred. The
      histopathology of the resected papules suggested epidermoid carcinoma or
      trichilemmal carcinoma, mainly localized within the lymphatics of the upper
      dermis. Re-examination of the first skin tumor and electron microscopy of the
      tumor obtained at autopsy revealed that both tumors were MEP. Although the
      metastases to the local cutaneous regions and lymph nodes via the lymphatics
      occur in 20% of MEP, cases with multiple visceral metastases are very few.

PMID- 9001991
TI  - Dermatomal lichenoid chronic graft-vs-host disease following varicella-zoster
      infection despite absence of viral genome.
AB  - Localized cutaneous graft-versus-host disease (GVHD) following a dermatomal
      distribution or in a pattern of Blaschko's lines. Some authors have postulated
      that dermatomal GVHD is triggered by a varicella-zoster virus infection, although
      in reported cases, there was no history of a preceding herpes zoster. We describe
      a case of GVHD localized to the exact dermatome of a culture-proven varicella
      zoster virus infection. PCR analysis failed to detect persistence of viral genome
      in the affected skin.

PMID- 9001990
TI  - Cornified cell envelope proteins and keratins are normally distributed in
      harlequin ichthyosis.
AB  - Long-term survivors of harlequin ichthyosis (HI) have raised a controversy over
      the differences between HI and lamellar ichthyosis (LI). Abnormal lamellar
      granules and the failure of conversion from profilaggrin to filaggrin have been
      reported in HI. On the other hand, malformation of the cornified cell envelope as
      a result of mutation of keratinocyte transglutaminase has been found in LI. In
      the present study, we analyzed the distribution of keratins,
      filaggrin/profilaggrin and cornified cell envelope proteins in the epidermis in
      HI. We studied a newborn Japanese male with typical clinical features of HI.
      Electron microscopic observation of a skin biopsy specimen taken from the trunk
      revealed the presence of lipid inclusions within the cornified cells, the absence
      of lamellar granules in the granular layer keratinocytes, and a lack of
      extracellular lamellar structures between the first cornified cell and the
      granular cell. Immunohistochemical labeling showed a normal distribution of
      keratins (keratins 1, 5, 10, and 14), filaggrin/profilaggrin and cornified cell
      envelope proteins (involucrin, small proline-rich proteins, and loricrin) in the
      epidermis of lesional skin. The present observations of the patient's skin
      verified that keratins and cornified cell envelope proteins are normally
      expressed in HI, thus demonstrating a different pathogenesis between HI and LI.

PMID- 9001992
TI  - Health outcomes research on Hispanics/Latinos.
AB  - Outcomes research studies the impact of the health and medical interventions on
      the health status and quality of life of the population. This paper discusses
      some of the issues and challenges involved in conducting health and medical
      outcomes research on the Latino population in the U. S., and also provides some
      solutions or strategies to overcome some of the most common problems in studying
      this population.

PMID- 9001993
TI  - Practice variations in treating urban minority asthmatics in Chicago.
AB  - This study explores provider adherence to national guidelines in treating Latino
      and African-American asthmatics. We hypothesized that there would be more
      variations in asthma treatment existing for minorities as a result of variation
      in physician's adherent to the guidelines. A 96-item survey was administered to
      138 Latino and African-American asthmatics attending a hospital emergency
      department. Data were obtained on demography, severity, access, patient
      satisfaction, and patient's assessment of physician asthma management. Results
      were analyzed by ethnicity, gender, practice site of regular provider, and
      severity. Variation in physician practice was found in these variables. Asthma
      treatment received by Latino and African-American respondents was deficient
      compared to guidelines. Regression analyses showed that Latinos fared more poorly
      on the number of prednisone bursts taken, use of written crisis plans and
      dispensation of peak flow meters controlling for gender, practice site and
      severity. African-Americans expressed less dissatisfaction in obtaining services,
      while both groups expressed high degrees of satisfaction with their providers.

PMID- 9001994
TI  - Factors affecting diabetes treatment and patient education among Latinos: results
      of a preliminary study in Chicago.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem among
      Latinos, yet the quality of diabetes treatment among them has not been fully
      examined. GOALS: A pilot study was conducted with adult diabetic patients for the
      purposes of describing their diabetes-related knowledge and behaviors and
      evaluating whether these patients were receiving effective outpatient care.
      METHODS: Demographic data, health knowledge, and behavioral information was
      collected using face-to-face interviews with 101 patients diagnosed for at least
      1 year at three primary care clinics. The medical record of each interviewee was
      abstracted for evidence that medical follow-up was being conducted with the
      recommended frequency. RESULTS: Most respondents spoke only or mostly Spanish,
      yet 14% of these patients reported that they had received instruction about
      diabetes in English alone. A majority of patients exhibited a basic understanding
      of their disease, and more than half reported positive health behaviors within
      the past year. Nonetheless, 54% of Puerto Rican Americans and 26% of Mexican
      Americans had been admitted to the hospital or had used the emergency room for
      diabetes-related conditions. Recommended medical procedures were infrequently
      documented in clinic records. CONCLUSIONS: Diabetes education was available in
      Spanish, and patients appeared to have a basic knowledge of the disease process.
      However, recommended clinical follow-up was not uniformly provided. The large
      number of diabetes-related hospitalizations may be related to sub-optimal
      management among at least some of these patients.

PMID- 9001996
TI  - Indicators of oral health in diverse ethnic and age groups: findings from the
      International Collaborative Study of Oral Health Outcomes (ICS-II) USA research
      locations.
AB  - Racial-ethnic group differences are assessed using a standardized set of oral
      health indicators, as well as various predisposing, enabling and need
      characteristics collected in the International Collaborative Study of Oral Health
      Outcomes (ICS-II) USA research locations. The unique data set contains comparable
      data on African-American, Native American, Hispanic, primarily Mexican-American,
      and White adults. Age group differences in oral health indicators are also
      compared in two adult age cohorts (35-44 and 65-74 years). Since data were
      collected from geographically diverse regions of the United States, differences
      in oral health indicators are considered within the context of different dental
      care delivery systems and external environments. Results indicate that the gap in
      oral health between Whites and ethnic minority groups is pervasive across
      research locations and age cohorts. Variation in regional dental care delivery
      systems and the varying effects of race-ethnicity and age cohort suggest that
      alternative health promotion strategies will be needed for improving oral health
      in diverse populations.

PMID- 9001997
TI  - The role of Latino/Hispanic communities in health services research: strategies
      for a meaningful partnership.
AB  - This paper critically assesses the important elements of the Latino/Hispanic
      community's participation in health services research and the known barriers to
      effective collaboration, and provides suggestions that may contribute toward a
      meaningful partnership among health care providers, researchers and the
      community. The discussion focuses on central strategies for community
      participation to help improve existing health care services' effectiveness,
      specifically for low-income Latino/Hispanic groups. It reviews current approaches
      for including communities in health care delivery and health services research
      and draws examples from the author's experiences of working with Latino/Hispanic
      communities for almost 20 years. The data implies that mutual benefits can be
      derived from forging alliances and meaningful partnerships between the health
      services research community and the Latino/Hispanic community.

PMID- 9001995
TI  - Risk factors for invasive cervical cancer in Latino women.
AB  - Most invasive cervical cancer research in the United States has been conducted on
      non-Latino-White (NLW) and African-American women. Incidence, mortality, stage at
      diagnosis and survival indicators for invasive cervical cancer in Latino women in
      California are compared to NLW and African-American women. A model is presented
      which depicts structural, behavioral, genetic and biological risk factors for
      invasive cervical cancer. A literature review of risk factors and their
      association with invasive cervical cancer was conducted using MEDLINE and
      PsychINFO databases to determine if ethnic differences in risk factors explain
      observed differences in morbidity and mortality. Latino women experience a
      significantly higher incidence and mortality associated with invasive cervical
      cancer than NLW women. The review of risk factors found that rate differences of
      cervical cancer screening, early detection and human papilloma virus (HPV) type
      specific infection explain much of the disparity in disease burden. Further
      research must clarify if ethnic differences exist in risk factors associated with
      ethnic variation in HPV-type prevalence in both cases and their sexual partners,
      in host immune responses, and multiparity.

PMID- 9001998
TI  - Prenatal care experiences and birth weight among Mexican immigrant women.
AB  - National studies indicate that Mexican immigrant women tend to have more positive
      birth outcomes than other groups, despite receiving relatively low levels of
      medical prenatal care. Our study-based on in-depth interviews with immigrant
      women who had recently given birth in Chicago-examines women's experiences
      seeking prenatal care. Qualitative findings contribute to understanding why many
      of these women received less than optimal care during pregnancy. The study also
      offers modest evidence that, despite overall positive birth outcomes and low
      levels of prenatal care, adequate prenatal care may make a difference in birth
      outcomes in this group. Suggestions are made concerning ways to improve access to
      adequate care, paying particular attention to the impact of migration and
      communication in prenatal care.

PMID- 9001999
TI  - Challenges and opportunities in establishing a Latino health research center in a
      majority academic institution.
AB  - This article provides a practical perspective of the issues, challenges and the
      opportunities involved in establishing a Latino Health Research Center in an
      academic institution. This article will use as an illustration the experiences
      related to the establishment of a Center on Latino Medical Treatment
      Effectiveness Program at a large public academic institution in Chicago. Some of
      the sociopolitical processes of establishing the Center's structure, and the
      recruitment and training of a multi-disciplinary core research staff are
      summarized, while simultaneously pursuing an ambitious research and training
      agenda. The article ends by suggesting a series of strategies in meeting the
      multiple and, at times, conflicting demands of the academic institution, the
      funding sources and the community, as well as the lessons learned.

PMID- 9002000
TI  - Hispanic/Latino health outcomes research. Introduction to special issue.

PMID- 9002001
TI  - The hospital course in total hip and knee arthroplasty: which length of stay is
      right?

PMID- 9002002
TI  - Costs of illness and the burden of disease.

PMID- 9002003
TI  - The continuing challenge of predictive factors in rheumatoid arthritis:
      prediction or association?

PMID- 9002004
TI  - The acute phase and function in early rheumatoid arthritis. C-reactive protein
      levels correlate with functional outcome.
AB  - OBJECTIVE: To discover whether normalization of C-reactive protein (CRP) in
      patients with rheumatoid arthritis (RA) results in stabilization of their
      functional state, and whether a measure of disease activity can be used as a
      predictor of functional outcome. To examine the relationship between change of
      CRP and Health Assessment Questionnaire (HAQ) over a 24 mo period to define the
      sensitivity of HAQ to change. METHODS: A prospective study of 109 consecutive
      patients who fulfilled the American College of Rheumatology criteria for RA and
      had elevated CRP before steroid or 2nd line therapy. A full clinical assessment
      including HAQ was performed at presentation and at 3, 6, 12, and 24 mo. On the
      basis of the change in CRP at 6 mo, patients were divided into 3 groups: (1) CRP
      suppression to normal, (2) 50% reduction in CRP, and (3) less than 50% CRP
      change. RESULTS: The 3 groups were clinically and immunologically similar at
      onset. At 6 mo the median HAQ fell to 5 (lower to upper quartiles 7.5 to 19) in
      Group 1 (CRP normalized, n = 34), 6 (3.75 to 10) in Group 2 (CRP reduced by 50%,
      n = 30), and 12 (6 to 18) in Group 3 (less than 50% CRP change, n = 44), p <
      0.005 for Groups 1 and 2 versus Group 3. At 12 and 24 mo HAQ remained
      significantly lower in Groups 1 and 2 compared with Group 3. In Group 1, patients
      either maintained a normal CRP (n = 28) or their CRP became elevated (n = 6).
      Only in those patients in whom a re-elevation of the CRP occurred was
      deterioration in HAQ subsequently seen. CONCLUSION: Suppression of elevated CRP
      in patients with active RA is associated with improvement in functional score,
      whereas persistent elevation of CRP is associated with functional deterioration.
      Once abnormal CRP is suppressed, no functional deterioration is likely to occur
      without re-elevation in CRP. Therefore, elevated CRP provides a convenient short
      term correlation with functional outcome and can be used as a guide for therapy.
      A HAQ score is a sensitive indicator of change in early disease.

PMID- 9002005
TI  - Rheumatoid arthritis exhibits reduced acute phase and enhanced constitutive serum
      amyloid A protein in synovial fluid relative to serum. A comparison with C
      reactive protein.
AB  - OBJECTIVE: There are 2 classes of serum amyloid A (SAA) protein, acute phase (A
      SAA) and constitutive (C-SAA). Hepatic synthesis of A-SAA is dramatically
      upregulated by inflammatory cytokines, while C-SAA is constitutively produced in
      the absence of inflammation. A-SAA has been shown to attract monocytes,
      neutrophils, and T lymphocytes, but the function of C-SAA remains to be
      determined. SAA proteins have been found in both serum and synovial fluid (SF) of
      patients with rheumatoid arthritis (RA), but have not been characterized with
      respect to isoform distribution. We determined the relative distribution of A-SAA
      and C-SAA in serum and SF of patients with RA and compared their abundance to the
      classic acute phase response protein, C-reactive protein (CRP). METHODS: A-SAA
      (isoforms SAA1, SAA2) and CRP were measured by commercially available ELISA kits.
      ELISA were developed for C-SAA (SAA4) and apolipoprotein AI (apo AI) in paired
      serum and SF from 56 patients with RA. RESULTS: Concentrations (mean +/- SD) of A
      SAA (SAA1,2) in serum and SF are 124 +/- 247, 20 +/- 32 micrograms/ml; CRP 75 +/-
      70, 33 +/- 37 micrograms/ml; C-SAA (SAA4) 106 +/-49, 91 +/- 39 micrograms/ml; and
      apo AI 1.19 +/- 0.32, 0.37 +/- 0.12 mg/ml, respectively. CRP correlated
      positively with A-SAA in serum or SF and negatively with apo AI in serum. There
      was no correlation with apo AI in SF. In contrast, there was no correlation
      between C-SAA and CRP, A-SAA, or apo AI in serum or in SF. Median concentrations
      of A-SAA in serum and SF (44, 10 micrograms/ml) and CRP (46, 20 micrograms/ml),
      respectively, markedly differed from the mean values, whereas median
      concentrations of C-SAA (104, 85 micrograms/ml) and apo AI (1.17, 0.37 mg/ml),
      respectively, did not. CONCLUSION: C-SAA concentrations vary in serum and SF
      independently of A-SAA and CRP levels. The lower concentration of A-SAA relative
      to C-SAA and CRP in SF suggests that A-SAA could be selectively catabolized in SF
      or alternatively not well transported into the synovial space.

PMID- 9002006
TI  - Individual relationship between progression of radiological damage and the acute
      phase response in early rheumatoid arthritis. Towards development of a decision
      support system.
AB  - OBJECTIVE: Evaluation of the individual relationship between C-reactive protein
      (CRP) production or erythrocyte sedimentation rate (ESR) and progression of
      radiologic damage in early rheumatoid arthritis (RA), to improve the predictive
      value of monitoring the acute phase response. METHODS: The relationship was
      modeled mathematically using adjustments for discontinuity in the radiographic
      scoring system and for clustering in the occurrence of score points in the
      initial phase. The model was evaluated in a prospective study of 149 patients
      with early RA, monthly CRP assays, and 6-monthly Sharp scores of radiographs of
      the hands and feet. RESULTS: Time integrated CRP values correlated closely with
      radiologic progression in each patient, but there was considerable variation
      between individuals with similar radiographic scores. The theoretical model
      accommodated these results, and based on CRP measurements and radiographic scores
      over 6 months, it provided a k value for each patient that reflected the
      individual relationship between CRP and radiologic damage. Using this k value
      combined with actual CRP levels over 3 and 6 years, the model accurately
      predicted the extent of radiologic progression that was actually observed at
      these times. Best results were obtained using estimation of the k value from 6 or
      12 month observational data. The model has been incorporated into a software
      program for routine clinical use that indicates the levels to which CRP should
      fall to prevent further joint damage. Similar results were obtained for ESR.
      CONCLUSION: A model has been established defining the individual relationship
      between time integrated CRP and ESR values, reflecting rheumatoid disease
      activity, and progression of radiologic damage. It accurately prediets outcome
      from 6 months after presentation and can be used as a practical decision support
      system.

PMID- 9002007
TI  - Prediction of articular destruction in rheumatoid arthritis: disease activity
      markers revisited.
AB  - OBJECTIVE: To assess the predictive value for joint damage progression of
      commonly used disease activity or process measures in rheumatoid arthritis (RA).
      METHODS: Seventy-two patients fulfilling the American Rheumatism Association
      criteria for RA were assessed twice yearly for 2 years. Primary outcome variables
      were progression of articular destruction, evaluated by Sharp's method, for 6,
      12, 18, and 24 month periods. RESULTS: Regression analysis, using random effects
      linear models, showed that only C-reactive protein, alpha 1-acid glycoprotein,
      iron, and erythrocyte sedimentation rate were significantly, but not
      independently, associated with 6 month radiographic progression. Traditional
      clinical measures were not predictive. No assessed marker was able to predict
      longer term outcome (12 or 18 month joint damage progression). Recent onset
      disease and older age were also associated with more severe radiographic
      progression. CONCLUSION: The lack of association between clinical measures and
      laboratory markers as predictors of the progression of articular destruction is
      further evidence of the need to reconsider processes and outcomes in RA. This
      study also suggests that clinical measures and laboratory markers probably do not
      reflect the same underlying process, arguing against gathering these measures
      under the same heading of "disease activity measures".

PMID- 9002008
TI  - Rheumatology visit frequency and changes in functional disability and pain in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine if the frequency of visits to rheumatologists by patients
      with rheumatoid arthritis (RA) is associated with either short term (6 month) or
      longterm (10 year) changes in functional disability or pain. METHODS: Information
      on health care utilization and health status was obtained for up to 10 years by
      biannual mailed Health Assessment Questionnaires (HAQ) in a community based
      cohort of patients with RA. We studied the relationship between the frequency of
      visits to rheumatologists and changes in functional disability and pain among 127
      patients who were treated by a rheumatologist at least once each year. RESULTS:
      The median visit frequency was 7.2 visits/year (range 2-17.5 visits/year). The
      number of rheumatology visits was significantly associated with short term
      changes in both functional disability and pain: each additional visit in a 6
      month study interval was associated with a decrease in the pain score in the
      current interval by an average of 0.02 points (on a 3 point scale), and each
      additional visit was associated with a decrease in the HAQ Disability Index in
      the subsequent 6 month interval by an average of 0.007 points (on a 3 point
      scale). In analyses of longterm changes in health status, there was a U-shaped
      relationship between the frequency of rheumatology visits and the rate of
      progression of functional disability over time, with the lowest rates associated
      with average visit frequencies of between 7 and 11 visits/year. Average pain
      scores over time were positively correlated with the average annual frequency of
      rheumatology visits (r = 0.25). CONCLUSION: More frequent visits to
      rheumatologists were associated with greater improvements in pain and functional
      disability over periods of 6 and 12 months, respectively. Rates of progression of
      functional disability over time were also higher among patients with less than 7
      visits/year than among those with 7-11 visits/year, suggesting that the outcomes
      of these patients might have been improved with more frequent visits.

PMID- 9002009
TI  - Indirect and nonmedical costs among people with rheumatoid arthritis and
      osteoarthritis compared with nonarthritic controls.
AB  - OBJECTIVE: Compared to rheumatoid arthritis (RA), osteoarthritis (OA) is
      considered much more benign and much less costly. We sought to describe the
      economic effects of RA and OA, in terms of the indirect and nonmedical
      expenditures, compared to nonarthritic controls. METHODS: Using our unique
      population based data resources, we developed a model for estimating and
      comparing disease specific costs among 2 randomly selected, community based
      samples of 200 patients each with RA and OA and a control group of 200
      individuals from the same community who do not have arthritis. Data were
      collected using a pretested postal survey. Age and sex adjusted comparisons were
      conducted across the 3 groups, and predictors of cost and utilization were
      identified using logistic regression modeling. RESULTS: There were 123, 116, and
      94 respondents among the RA, OA, and nonarthritis groups, respectively. The
      average age and the female-to-male ratios were higher in the OA and RA groups
      compared to the nonarthritis group. Patients with RA and OA required 3 times more
      days of care for their conditions compared to nonarthritics (p < 0.0001) and
      incurred significantly more expenditures for home or child care (p = 0.01) and
      other services (p = 0.001) (i.e., medical equipment, assistive devices, or home
      remodeling) compared to nonarthritics. In addition, patients with RA were
      significantly more likely to have lost their job or to have retired early due to
      their illness (p = 0.001); were the most likely to have reduced their work hours
      or stopped working entirely due to their illness (p = 0.003); and were 3 times
      more likely to have had a reduction in household family income than either
      individuals with OA or those without arthritis (p = 0.0001). Fifteen percent of
      respondents with RA were unable to get a job because of their illness, while 3%
      of respondents with OA and only 1% of nonarthritic respondents reported this
      experience (p = 0.001). Logistic regression analysis revealed that functional
      status and pain score, as well as the presence of either RA or OA, were
      significant predictors of cost and health services utilization. CONCLUSION:
      Disease specific indirect and nonmedical costs for OA are substantial and
      approach those for RA. This has important societal implications, given the high
      prevalence of OA.

PMID- 9002010
TI  - Dosing implications of a clinical interaction between grapefruit juice and
      cyclosporine and metabolite concentrations in patients with autoimmune diseases.
AB  - OBJECTIVE: To determine the effect of chronic grapefruit juice administration on
      steady state blood concentrations of cyclosporine and metabolites in patients
      with autoimmune diseases. METHODS: 9 patients stabilized on administration of
      cyclosporine (range 0.7-6.7 mg/kg/day) were given either grapefruit juice or
      water using randomized crossover design. Whole blood samples were collected
      before the morning cyclosporine dose and during the 12 h interdose interval.
      Cyclosporine concentrations were measured using a relatively specific assay
      (Emit) and total metabolite concentrations were estimated using a nonspecific
      assay (polyclonal Abbott-TDx). RESULTS: Exposure to grapefruit juice produced
      significant increases in predose cyclosporine concentrations (p < 0.01) and total
      metabolite concentrations (p = 0.03) and the area under the cyclosporine and
      metabolite blood concentration-time curves (p = 0.005, p = 0.001, respectively).
      One patient developed significant neurological side effects associated with a
      68.9 and 214% increase in predose cyclosporine and metabolite concentrations,
      respectively, during grapefruit juice co-administration. CONCLUSION: Grapefruit
      juice causes an increase in both parent and metabolite profiles, indicating an
      alteration in the disposition of cyclosporine and metabolites. This interaction
      is of potential clinical importance in terms of mechanism, side effects, and
      dosing.

PMID- 9002011
TI  - Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha,
      interleukin 6, and interferon-gamma production by peripheral blood mononuclear
      cells.
AB  - OBJECTIVE: The efficacy of both chloroquine and hydroxychloroquine in rheumatoid
      arthritis (RA) has been proved in controlled clinical trials. Despite similar
      chemical characteristics, it is believed the clinical efficacy of chloroquine is
      superior to that of hydroxychloroquine in patients with RA. Excessive production
      of proinflammatory cytokines was shown to contribute to the pathogenesis of RA.
      From different studies testing either chloroquine or hydroxychloroquine, it could
      be concluded that both drugs differentially inhibit cytokine production. METHODS:
      We compared the effects of both chloroquine and hydroxychloroquine on stimulated
      peripheral blood mononuclear cells (PBMC) with respect to cytokine production.
      Therefore, PBMC were tested for tumor necrosis factor-alpha (TNF-alpha),
      interleukin 6 (IL-6), and interferon-gamma (IFN-gamma) by specific ELISA, after
      stimulation with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) in the
      presence or absence of different concentrations of chloroquine or
      hydroxychloroquine. RESULTS: We observed that chloroquine and hydroxychloroquine
      equally inhibit PHA induced TNF-alpha and IFN-gamma production, and LPS induced
      TNF-alpha and IL-6 production, while PHA induced IL-6 production was not
      affected. CONCLUSION: Chloroquine and hydroxychloroquine display similar effects
      on PHA and LPS induced cytokine production by PBMC under identical in vitro
      conditions. These findings may help in understanding the mechanism of action of
      these drugs on RA.

PMID- 9002012
TI  - Ongoing immunologic activity after short courses of pulse cyclophosphamide in the
      NZB/W murine model of systemic lupus erythematosus.
AB  - OBJECTIVE: Short courses of intermittent pulse cyclophosphamide (CY) have
      mitigated ovarian toxicity but have also led to incomplete or unsustained
      remissions of active systemic lupus erythematosus (SLE) in many patients,
      prompting an evaluation of the immunologic effects of this regimen in the NZB/W
      female mouse (B/W) model of human SLE. METHODS: Phenotypic and functional
      characteristics of spleen lymphocytes from B/W mice treated with short courses of
      intraperitoneal (i.p.) CY were compared to those from untreated control B/W mice.
      RESULTS: After a single dose (250 mg/kg) of i.p. CY, spleen lymphocyte
      subpopulations fell abruptly but recovered within 4 weeks. Four monthly doses of
      i.p. CY (starting at 5 months of age) led to a sustained reduction in spleen
      lymphocyte subpopulations and a parallel decrease in the number of spleen cells
      spontaneously secreting immunoglobulin and anti-DNA antibody to about 30% of the
      number seen in untreated control B/W mice. Lipopolysaccharide induced secretion
      of total IgG and IgG anti-DNA by cultured spleen cells was not diminished one
      month after the 4 month course of i.p. CY. CONCLUSION: The 4 month course of i.p.
      CY produced a marked reduction in the number of activated B cells producing
      autoantibody, but did not achieve sustained immunomodulation judged by the
      unaltered proportion of spleen B cells spontaneously secreting immunoglobulin and
      anti-DNA, as well as the response to polyclonal activators of B cells. These
      results suggest a continued susceptibility to flares of SLE activity after brief
      courses of intensive immunosuppressive therapy.

PMID- 9002013
TI  - Antiphospholipid antibodies in patients with eosinophilia myalgia and toxic oil
      syndrome.
AB  - OBJECTIVE: To explore whether antiphospholipid antibodies (aPL) are markers of
      vascular related damage or merely evidence of toxic related autoimmunity, we
      investigated the presence of different aPL in patients with toxic oil syndrome
      (TOS) and compared the profile with patients with eosinophilia myalgia syndrome
      (EMS). METHODS: Reactivity against cardiolipin, P-serine, P-inositol, and P
      choline was investigated by ELISA in the blood of 266 patients with acute and
      chronic TOS, 25 healthy relatives of TOS patients, and 48 patients with EMS.
      RESULTS: 32% of TOS and 13% of EMS patients had IgG antibodies against
      cardiolipin and other polyanions. 20% of both TOS and EMS patients presented IgM
      antibodies against anionic and zwitterionic phospholipids. 36% of TOS healthy
      relatives had IgM antibodies against differently charged phospholipids. Among 200
      patients with chronic TOS, there was no significant association between
      antibodies and clinical manifestations. CONCLUSION: aPL with different
      specificity are present in a high percentage of patients with TOS and EMS. The
      significance of these antibodies remains unclear.

PMID- 9002014
TI  - The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993.
AB  - OBJECTIVE: To determine the incidence, prevalence, survival rates, clinical
      manifestations, and longterm outcome of patients with morphea (localized
      scleroderma) and its subtypes over a 33 year period in Olmsted County, Minnesota.
      METHODS: We used the unique data resources of the Rochester Epidemiology Project
      to review all Olmsted County medical records with any potential diagnosis
      consistent with morphea (including plaque, generalized, bullous, linear, and deep
      entities) from 1960 through 1993. RESULTS: We screened 1030 medical records and
      identified 82 (59 female; 23 male) cases of morphea first diagnosed between 1960
      and 1993. All cases were followed until death or migration from Olmsted County, a
      total of 754 person-years of observation. The annual age and sex adjusted
      incidence rate per 100,000 population was 2.7 (95% confidence interval 2.1, 3.3).
      The incidence rate increased significantly over the 33 years (p = 0.0037) on an
      average of 3.6% per year. The prevalence (estimated using cumulative incidence)
      at 80 years of age was about 2/1000. 50% of the patients had a cutaneous
      softening or evidence of disease resolution by 3.8 years' duration. The shortest
      active disease duration was found in the plaque group (50% resolution or skin
      softening by 2.7 years) compared to 5.5 years in the deep group. Arthralgias,
      synovitis, uveitis, and joint contractures were more frequent in the linear and
      deep categories. Although 9 patients (11%) developed some disease related
      disability over the followup period, this was common (44%) in the deep group. No
      case of morphea developed severe internal organ involvement and none progressed
      to systemic sclerosis. The survival rate was not significantly different from the
      general population (p = 0.409). CONCLUSION: Morphea, and its subtypes, are more
      common than previously recognized, and can lead to important disability.

PMID- 9002015
TI  - Relationship between cutaneous and pulmonary involvement in systemic sclerosis.
AB  - OBJECTIVE: Pulmonary disease may shorten survival in patients affected by
      systemic sclerosis (SSc). However, pulmonary involvement may commonly be silent,
      whereas skin fibrosis is usually the clinical feature drawing most attention. We
      investigated the relationship between cutaneous and pulmonary involvement during
      SSc. METHODS: We studied 52 patients (mean age 50.2 +/- 13.7 years) affected by
      SSc (mean duration of disease 13.8 +/- 9.5 years). Twenty-eight had the diffuse
      form of the disease (dSSc) and 24 the limited form (lSSc). All patients underwent
      pulmonary function studies, high resolution computed tomography (HRCT) of the
      lungs, and complete echocardiographic examination. Pulmonary artery systolic
      pressure was measured by Doppler echocardiography. Pulmonary interstitial
      fibrosis and skin fibrosis were evaluated using a point system. RESULTS: Mean
      percentages of predicted values of forced vital capacity and total lung capacity
      were significantly reduced in patients with dSSc compared to lSSc (80.0 +/- 18.9
      vs 98.4 +/- 16.8%, p < 0.001; and 81.3 +/- 13.9 vs 92.1 +/- 14.2%, p < 0.01,
      respectively). The overall HRCT score was 6.1 +/- 4.9, with no significant
      differences between disease subgroups. However, a HRCT score of 10 or more was
      present in 10 patients with dSSc vs 2 patients with lSSc (p = 0.02). Pulmonary
      hypertension was present in 27 patients, 15 with lSSC and 12 with dSSc (p = NS).
      No significant correlation was observed between skin score and lung volumes,
      carbon monoxide diffusing capacity, HRCT score, or pulmonary artery systolic
      pressure for all patients and subgroups. CONCLUSION: Extent and severity of
      cutaneous and pulmonary involvement in SSc are not directly correlated.
      Nevertheless, different patterns of pulmonary involvement between SSc subgroups
      were observed. Restrictive lung disease was more frequent in patients with dSSc,
      while a trend to higher prevalence of pulmonary hypertension was observed in
      patients with lSSc.

PMID- 9002016
TI  - Autoantibodies to myeloperoxidase in systemic sclerosis.
AB  - OBJECTIVE: Although antimyeloperoxidase (MPO) antibodies provide a sensitive
      serological test for vasculitis, their significance in sera from a small
      proportion (about 10%) of patients with autoimmune rheumatic disease is
      controversial. Our aim was to determine the incidence of anti-MPO antibodies in
      sera from patients with systemic sclerosis (SSc) and their relation to renal
      disease. METHODS: Thirty-eight patients had limited cutaneous SSc (lSSc) and 43
      diffuse cutaneous SSc, and within each group, 24 and 27 patients, respectively,
      had renal impairment (defined as stable creatinine clearance less than 60
      ml/min). Six patients previously had had a scleroderma renal crisis. After
      screening for antineutrophil cytoplasmic antibodies (ANCA) by indirect
      immunofluorescence, the levels of IgM and IgG anti-MPO antibodies in 8 patients
      with SSc was determined by ELISA, with human MPO as antigen. RESULTS: Sera from 2
      patients, both with lSSc and renal impairment, were perinuclear p-ANCA positive
      and had significant levels of circulating IgM and IgG anti-MPO antibodies. In one
      patient, anti-MPO antibodies appeared in the serum only after D-penicillamine was
      introduced, continued to rise after withdrawal of the drug, and fell only after
      immunosuppressive therapy. Renal biopsy confirmed vasculitis. The 2nd patient
      died of unrelated disease before further investigations could be performed.
      CONCLUSION: We suggest that circulating anti-MPO antibodies are not a feature of
      SSc per se and, if found, may indicate the presence of an unrelated pathology,
      such as idiopathic or drug induced vasculitis.

PMID- 9002017
TI  - Basic fibroblast growth factor inhibits basal and transforming growth factor-beta
      induced collagen alpha 2(I) gene expression in scleroderma and normal
      fibroblasts.
AB  - OBJECTIVE: Studies have shown that scleroderma (systemic sclerosis, SSc) and
      normal fibroblasts respond differently to basic fibroblast growth factor (bFGF),
      SSc fibroblasts being less responsive than normal fibroblasts in mitogenic assays
      in vitro, bFGF also stimulates the expression of platelet derived growth factor
      alpha (PDGF-alpha) receptors in normal fibroblasts, but not in SSc fibroblasts.
      Conversely, transforming growth factor-beta (TGF-beta) stimulates PDGF-alpha
      receptor expression in SSc fibroblasts, but not in normal fibroblasts. Since bFGF
      has been shown to inhibit collagen gene expression in several cell types, we
      examined responses of SSc and normal fibroblasts to bFGF alone and in combination
      with TGF-beta with regard to collagen alpha 2(I) (COL1A2) expression. METHODS:
      Fibroblasts were obtained by skin biopsy from affected areas of patients with
      diffuse cutaneous SSc and from healthy donors and propagated in vitro. The
      effects of bFGF and TGF-beta on the COL1A2 mRNA expression levels in SSc and
      healthy fibroblasts were analyzed by Northern blot. The effects of bFGF on the
      COL1A2 promoter activities in both cell types were analyzed by transient
      transfection assays. The effects of bFGF and TGF-beta on collagen protein
      synthesis were analyzed by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis and fluorography. RESULTS: While bFGF diminished COL1A2 mRNA in
      both SSc and normal cells, COL1A2 mRNA quantities in the SSc fibroblasts were not
      depressed to the levels expressed by normal controls. As anticipated, TGF-beta
      strongly induced COL1A2 mRNA levels in normal fibroblasts, and to a lesser degree
      in SSc fibroblasts. When cells were incubated with both TGF-beta and bFGF, the
      stimulatory effect of TGF-beta was completely suppressed in both cell types. bFGF
      decreased COL1A2 promoter activity in both cell types, suggesting that COL1A2
      inhibition by bFGF occurs at least partially at the transcriptional level. The
      effects of bFGF and TGF-beta on the collagen protein synthesis correlated well
      with mRNA data, in that TGF-beta stimulated, while bFGF strongly inhibited,
      collagen synthesis. CONCLUSION: bFGF is a potent inhibitor of basal and TGF-beta
      stimulated collagen expression in human fibroblasts, and this effect is not
      different between SSc and healthy fibroblasts.

PMID- 9002018
TI  - Relapsing polychondritis: clinical and immunogenetic analysis of 62 patients.
AB  - OBJECTIVE: In this study we describe clinical and immunogenetic findings in 62
      unselected patients with relapsing polychondritis. METHODS: In a multicenter
      study, clinical data of 26 (41.9%) female and 36 (58.1%) male patients were
      collected. HLA-DR specificities were identified in 60, and the frequencies were
      compared with those in healthy controls. RESULTS: The median age at the time of
      diagnosis was 46.6 years (range 17 to 86). 58 (93.5%) patients had auricular
      chondritis, 31 (50.0%) ocular symptoms, 35 (56.5%) nasal involvement. Involvement
      of joints (53.2%), respiratory system (30.6%), skin (24.2%), cardiovascular
      system (22.6%), central nervous system (9.7%), and kidneys (6.5%) was found as
      well. 22 (35.5%) patients had associated diseases such as systemic lupus
      erythematosus or rheumatoid arthritis. Susceptibility to relapsing polychondritis
      was significantly associated with HLA-DR4 (p < 0.001). There was no difference in
      the frequency or distribution of DRB1*04 subtype alleles between patients and
      healthy controls. The extent of organ involvement was negatively associated with
      HLA-DR6 (p < 0.011). CONCLUSION: Immunogenetic findings as well as similarities
      and overlapping clinical symptoms with other autoimmune or rheumatic diseases
      suggest that immunological mechanisms play a major role in the pathogenesis of
      relapsing polychondritis.

PMID- 9002019
TI  - Immunogenetic and microbial factors in acute anterior uveitis.
AB  - OBJECTIVE: To characterize the rheumatic diseases associated with acute anterior
      uveitis and examine the potential role of Yersinia enterocolitica in the
      pathogenesis of acute anterior uveitis. METHODS: 44 patients with acute anterior
      uveitis were assessed for evidence of an underlying rheumatic syndrome by history
      and examination. HLA profiles were identified by serologic and molecular
      techniques. Serological analysis of patients' sera for the presence of antibodies
      to Y. enterocolitica was by Western blot. RESULTS: 30 of the 44 patients had
      musculoskeletal symptoms. Of these, 8 had ankylosing spondylitis, 4 reactive
      arthritis, 2 undifferentiated spondyloarthropathy (SpA), 2 inflammatory bowel
      disease, one seronegative polyarthritis, and 13 mechanical back pain. Of 42
      patients typed, 29 (69%) were HLA B27 positive and an additional 7 patients
      expressed a crossreactive group antigen (86% of total group B27 or CREG
      positive). Western blot analysis of the sera revealed increased frequency of
      antibodies to Yersinia compared with a control population. Antibodies directed
      against the 36 and 27 kDa Yersinia antigens were recognized with greater
      frequency (p < 0.05) in patients with acute anterior uveitis than in controls.
      IgG reactivity was more pronounced than IgA reactivity. Adsorption studies showed
      significant cross reactivity of anti-Yersinia antibodies with Salmonella
      typhimurium. Among the patients with acute anterior uveitis anti-Yersinia
      reactivity did not correlate with the HLA profile, nor with the presence of an
      underlying rheumatic disease. CONCLUSION: SpA represent the commonest underlying
      rheumatic disorders associated with acute anterior uveitis. The majority of
      patients with acute anterior uveitis possess HLA-B27 regardless of whether there
      is underlying SpA. Patients with acute anterior uveitis show increased frequency
      of anti-Yersinia antibodies compared with controls. Many of these antibodies
      appear to be directed against antigenic determinants shared among gram negative
      bacteria and thus cannot constitute definitive evidence for a causal role
      specifically for Yersinia in acute anterior uveitis. Acute anterior uveitis
      represents an interplay of host susceptibility and microbial triggers, as is the
      case for the SpA in general.

PMID- 9002020
TI  - Antibodies to Klebsiella, Proteus, and HLA-B27 peptides in Japanese patients with
      ankylosing spondylitis and rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether patients with ankylosing spondylitis (AS) and
      patients with rheumatoid arthritis (RA) from Japan have antibodies to Klebsiella
      pneumoniae and Proteus mirabilis and to assess whether such antibodies are
      activated against peptides sharing sequences with HLA-B27. METHODS: Serum samples
      from 152 Japanese patients, 52 with AS, 50 with RA, and 50 healthy controls, were
      tested against 3 bacteria (K. pneumoniae, P. mirabilis, and Escherichia coli) and
      3 synthetic peptides (HLA-B27, pullulanase-D, and scrambled pullulanase-D control
      peptide) by ELISA under coded conditions. Samples were tested for elevations in
      IgG, IgA, and IgM antibody classes in patients with active AS or RA, in patients
      with RA with probable disease, and in patients with inactive AS. Disease activity
      was determined by an elevated serum C-reactive protein (> 10 mg/l) level and
      elevated erythrocyte sedimentation rate (> 20 mm/h). RESULTS: Patients with
      active AS showed specific elevations in serum IgA antibody levels against K.
      pneumoniae compared to patients with RA and controls (p < 0.001). No such
      elevation was seen in the IgG and IgM antibody classes. Patients with inactive AS
      showed no elevation in any class of antibody against K. pneumoniae compared to
      controls or patients with RA. Patients with active or probably active RA showed
      significant elevations in IgG antibody levels against P. mirabilis compared to AS
      and controls (p < 0.001). Patients with AS (active or inactive), RA (active or
      probably active), and controls showed no elevations in any antibody class to E.
      coli. Both active and inactive AS patients had specific autoantibodies against
      HLA-B27 peptide compared to patients with RA and controls (active AS: IgG, IgA,
      IgM, p < 0.001; inactive AS: IgG and IgA, p < 0.001). Patients with active AS had
      IgG and IgA antibodies against pullulanase-D peptide, which contains a sequence
      that cross reacts with HLA-B27 compared to controls (p < 0.001). CONCLUSION:
      These results provide the first evidence of AS and RA patients in Japan having
      specific elevations of antibody to K. pneumoniae and P. mirabilis, respectively.
      This suggests that K. pneumoniae in AS and P. mirabilis in RA may play a role in
      triggering and/or exacerbating these diseases.

PMID- 9002021
TI  - Murine progressive ankylosis is not immunologically mediated.
AB  - OBJECTIVE: Murine progressive ankylosis is an autosomal recessive disorder in
      mice similar to the human spondyloarthropathies. The gene responsible for
      progressive ankylosis, ank, has not been identified and its product is unknown.
      We investigated whether the immune system plays a role in the pathogenesis of
      progressive ankylosis. METHODS: Reciprocal transfers of spleen or bone marrow
      cells or serum between ank/ank and normal mice were performed. CD4 T cells were
      depleted in vivo by injection with monoclonal antibody. Ank/ank; nu/nu mice were
      bred from double heterozygote offspring of homozygote parents. RESULTS: Disease
      was neither ameliorated nor induced by these immune system manipulations.
      CONCLUSION: We conclude that progressive ankylosis is not immune mediated. The
      similarities between ankylosing spondylitis and murine progressive ankylosis may
      be due to mechanisms producing osteogenesis in nonosseous tissues.

PMID- 9002022
TI  - Magnetic resonance changes in the temporomandibular joint in ankylosing
      spondylitis.
AB  - OBJECTIVE: To evaluate temporomandibular joint (TMJ) involvement of patients with
      severe ankylosing spondylitis (AS) using magnetic resonance imaging (MRI).
      METHODS: All patients with severe cervical involvement, defined as occiput-wall
      distance > or = 3 cm and/or < 10 degrees of cervical flexion, from a consecutive
      cohort of 103 patients with AS were included in the study. Patients completed a
      questionnaire designed to evaluate symptoms of temporomandibular disorder (TMD).
      Open and closed mouth sagittal T1 weighted MRI sequences of the right TMJ was
      performed in all patients. MR images were specifically reviewed for condylar
      position and morphology, as well as articular disc position and morphology.
      RESULTS: Eleven patients were identified and included in the study.
      Temporomandibular symptoms were absent in 4 (37%), a single symptom was present
      in one (9%), 2 symptoms in one (9%), 3 symptoms in 3 (27%), and 4 symptoms in 2
      (18%). Ten of the 11 patients had abnormalities on MR, including condylar
      alterations such as abnormal shape, erosions, and reduction in translation. Disc
      alterations were present in 8 patients and osteophytes in 7. Two patients were
      graded as having mild abnormalities, another 2 as moderate, and the remaining 6
      were considered grossly abnormal. In 2 patients there were changes compatible
      with ankylosis of the right TMJ. CONCLUSION: Although it is uncommon for patients
      to complain spontaneously about TMD symptoms, involvement of the TMJ in patients
      with severe AS appears to be frequent and, in some, severe. The effect of TMJ
      involvement on the overall well being and nutritional status in patients with AS
      remains to be determined.

PMID- 9002023
TI  - Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Bechcet's
      disease; soluble TNFR-75 as a biological marker of disease activity.
AB  - OBJECTIVE: To analyze the levels of the T cell regulatory cytokines interleukin
      10 (IL-10) and IL-12 in plasma of patients with Behcet's disease (BD), and to
      assess the value of cytokines and cytokine antagonists as biological markers of
      disease activity. METHODS: Sera/plasma of 66 consecutive outpatients with
      established diagnosis of BD were analyzed for the presence of IL-2R, IL-6, tumor
      necrosis factor-alpha (TNF-alpha), soluble (s) TNF receptor (R)-55, sTNFR-75, IL
      10, and IL-12 using immunological methods. Additional laboratory measurements
      included erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Data
      from the history and clinical examination were recorded to correlate cytokine
      levels with clinical markers of disease activity. RESULTS: 18 patients had
      inactive (Group I), 36 had mildly active (Group II), and 12 patients had active
      BD (Group III). IL-10 was elevated in 42 plasma samples (64%). The percentage of
      samples containing IL-10 and the median levels of IL-10 of the 3 patient groups
      did not differ significantly. IL-12 was detectable in plasma of 9 patients: One
      from Group I (5%), 3 from Group II (8%), and 5 from Group III (41%). IL-12
      correlated with disease activity (difference between Groups I and III, p = 0.02,
      between Groups II and III, p = 0.008). ESR in patients with active disease and
      mildly active disease was significantly higher than values in patients with
      inactive disease (p = 0.03, p = 0.02, respectively), while median CRP levels were
      significantly different between Group I and Group III only (p = 0.006). sTNFR-75
      levels were significantly different between Groups II and III (p = 0.003) and
      between Groups I and III (p = 0.008). CONCLUSION: The elevation of plasma IL-10
      in the majority of patients and the correlation of IL-12 plasma levels with
      disease activity suggest a pathogenic role of a TH1-type immune response in
      active disease. In addition, the correlation of sTNFR-75 levels with disease
      activity indicates that sTNFR-75 may serve as a biological marker of disease
      activity in BD.

PMID- 9002024
TI  - In vitro magnetic resonance microimaging of experimental osteoarthritis in the
      rat knee joint.
AB  - OBJECTIVE: To visualize articular changes during iodoacetate induced
      osteoarthritis (OA) of the rat knee using high resolution magnetic resonance
      imaging (MRI). METHODS: All images were acquired on a 8.5T microimager on ex vivo
      rat knees. After optimization studies, 3D spin echo sequences were used with TR
      1200 ms and TE 15 ms; 40 sagittal images were obtained with a resolution of 400 x
      60 x 60 microns. OA lesions were achieved by injecting 3 mg iodoacetate in the
      right knee joint (Day 0). Progression of OA changes was studied at Days 5, 10,
      15, 20, 30, 90 and corresponding radiographs and histological sections were
      obtained. RESULTS: Spin echo images of the normal rat knee clearly visualized
      cortical bone, calcified menisci, patella, and cruciate ligaments as dark
      regions. Cartilage and muscles appeared as intermediate signal. In some cases a
      trilaminar appearance of cartilage and growth plate was depicted. This appearance
      persisted at Day 5, although cartilage presented a marked loss of proteoglycans.
      After Day 10 the menisci appeared irregular and inhomogeneous. After Day 15, MRI
      showed important alterations of articular cartilage, predominant on weight
      bearing areas of femoral condyles. Osteophytic remodeling was also seen around
      the patella. From Day 20 to Day 90 anatomical changes progressively affected
      epiphyseal bone, leading to subchondral cysts and loss of its regular trabecular
      structure. CONCLUSION: High field MRI provides a sensitive method for
      investigating ex vivo focal erosions of cartilage and established osteochondral
      remodeling in experimental OA in the rat. In this model, microimaging provides
      more information about early modifications of cartilage and soft tissue than
      radiographic exploration, in good correlation with histological data.

PMID- 9002025
TI  - Bone scintigraphy in the canine cruciate deficiency model of osteoarthritis.
      Comparison of the unstable and contralateral knee.
AB  - OBJECTIVE: To examine the effects on 99mTc medronate (MDP) bone scintigraphy of
      unilateral anterior cruciate ligament (ACL) transection in the unstable and
      contralateral knee of dogs. METHODS: Bone scintigraphy was performed in 5 dogs at
      baseline and 6 and 12 weeks after ligament transection, with images of both knees
      obtained 3-4 h after intravenous injection of the radionuclide. An image of the
      T4-T5 vertebral region was also acquired as an internal standard. In 3 additional
      dogs, scintigraphy was performed at baseline and 5 1/2 weeks after sham ACL
      transection. RESULTS: A marked increase in uptake of 99mTc MDP was seen in the
      unstable knee. In contrast, in all but one case uptake in the contralateral knee
      did not increase significantly. Sham ligament transection had no effect on uptake
      of the radionuclide. CONCLUSION: Changes occur in subchondral bone as well as in
      articular cartilage in the unstable knee in this model. The bony changes, which
      could be either primary or secondary to early changes in the biomechanical
      properties of the cartilage, may contribute to the pathogenesis of cartilage
      damage. No appreciable effects on bone turnover in the contralateral knee could
      be proved in this study.

PMID- 9002026
TI  - Predicting length of stay after hip or knee replacement for rheumatoid arthritis.
AB  - OBJECTIVE: To identify predictors of the postoperative length of stay (LOS) after
      hip or knee replacement for rheumatoid arthritis (RA). METHODS: Demographic and
      clinical characteristics, medications, and postoperative course were abstracted
      from medical records of patients with RA who underwent total arthroplasties of
      the knee (TKA) or hip (THA) at our institution between 1987 and 1991. The
      relationship between these variables and the postoperative LOS was examined using
      life tables, linear regression, and multiple regression analyses. RESULTS: During
      the 5 years of the study, 137 patients with RA underwent 119 TKA and 105 THA. The
      average LOS was 16.9 +/- 8.7 days after THA and 19.5 +/- 11.4 days after TKA (p =
      0.08). Significantly longer LOS was associated with age > or = 55 years, female
      sex, non-white ethnicity, poor functional status, known positive rheumatoid
      factor, use of bone cement, and operating room (OR) time longer than 6 hours. In
      a multivariate regression model, a preoperative Steinbrocker functional class 3
      or 4 was associated with an increase in LOS of 3.98 days (95% confidence interval
      0.78, 7.18) and 7.14 days (2.59, 11.69), respectively, while a known positive
      rheumatoid factor predicted an increase in LOS of 2.76 days (0.17, 5.35). Among
      operative factors, the use of bone cement was associated with a LOS that was
      longer by 3.50 days (0.80, 6.20), and each hour increase in OR time with a delay
      in discharge of 1.75 days (1.18, 2.33). Major postoperative wound complications
      increased LOS by 16.46 days (11.40, 21.52). CONCLUSION: Preoperative functional
      status is an important determinant of the rate of recovery of functional
      independence after surgery. Strategies for decreasing LOS after hip or knee
      replacements include optimization of preoperative functional status, early
      surgical intervention, and prevention of wound complications.

PMID- 9002027
TI  - Dupuytren's disease: association with chronic diabetic complications.
AB  - OBJECTIVE: To evaluate the prevalence of Dupuytren's disease and its association
      with the clinical characteristics in subjects with type I (insulin dependent) and
      II (non-insulin dependent) diabetes. To examine the association between
      Dupuytren's disease and chronic diabetic complications. METHODS: We studied 297
      patients with type I [age (mean +/- SD) 33.2 +/- 10.0 yrs] and 139 with type II
      diabetes [age 61.3 +/- 12.3 yrs]. We investigated the presence of Dupuytren's
      disease, limited joint mobility, and the following complications: retinopathy,
      micro- and macroalbuminuria, and somatic peripheral symmetrical polyneuropathy
      (neuropathy). RESULTS: The prevalence of Dupuytren's disease was 14% in type II
      patients; prevalence was the same in both sexes. Dupuytren's was associated with
      age and duration of diabetes in type I patients (p < 0.001). Its presence was
      significantly related to retinopathy, neuropathy, limited joint mobility, and
      shoulder capsulitis in type I and to macroalbuminuria in type II patients, by chi
      squared test. However, all these associations, except to macroalbuminuria in type
      II subjects, disappeared when the confounding effect of age and duration of
      diabetes was controlled by logistic regression analysis. CONCLUSION: The
      prevalence of Dupuytren's was the same in type I and II subjects although type I
      subjects were younger. No sex difference of the prevalence of Dupuytren's was
      seen in patients with diabetes. The disease was associated with macroalbuminuria
      in type II subjects independent of time related variables. Other associations
      between Dupuytren's disease and diabetic complications were explained by time
      related variables in type I and in type II subjects.

PMID- 9002028
TI  - Community screening for rheumatic disorder: cross cultural adaptation and
      screening characteristics of the COPCORD Core Questionnaire in Brazil, Chile, and
      Mexico. The PANLAR-COPCORD Working Group. Pan American League of Associations for
      Rheumatology. Community Oriented Programme for the Control of Rheumatic Disease.
AB  - OBJECTIVE: (1) To adapt the Community Oriented Programme for the Control of
      Rheumatic Disease (COPCORD) Core Questionnaire (CCQ) for use as a rheumatic
      disease screening instrument in Spanish and Portuguese communities in Brazil,
      Chile, and Mexico, including translation and back translation, and assessment of
      cross cultural equivalence and reliability. (2) To determine the screening
      characteristics of the CCQ, specifically the sensitivity and specificity of
      Spanish and Portuguese versions for detecting cases of rheumatic disorder
      compared with a full clinical examination by a rheumatologist. (3) To determine
      the number of clinical examinations that could be avoided in population studies
      by applying the CCQ followed by a clinical examination in positive CCQ screenees.
      METHODS: Translation and assessment of cross cultural equivalence were conducted
      by practising rheumatologists in Brazil, Chile, and Mexico using standardized
      methods. Back translation was done by an independent rheumatologist (Brazil), a
      radiologist (Chile), and a general physician (Mexico). Interviewer agreement was
      assessed in all sites in a convenience sample. Sensitivity and specificity were
      assessed by independently administering the CCQ and a full clinical examination
      to a sample of 200 persons aged 15 years or older, randomly selected from
      communities in Sao Paulo, Brazil (n = 200), Temuco, Chile (n = 200), and Mexico
      City, Mexico (n = 200). RESULTS: (1) Cross cultural equivalence and back
      translation of the modified questionnaire were satisfactory. Interviewer
      agreement was acceptable. (2) In groups from Brazil, Chile, and Mexico,
      respectively, the overall prevalence of rheumatic disease based on clinical
      examination was 33.3, 45.1, and 46.3%. The sensitivity and specificity of 2
      definitions of a positive CCQ screening for the presence of rheumatic disorder
      were: Definition 1 (no trauma, present pain, tenderness, swelling or stiffness in
      bones, joints or muscles): sensitivity, 91.8, 96.0, 84.0; specificity, 70.0,
      35.5, 61.0; Definition 2 (Definition 1 plus pain intensity > or = 4 and 11 point
      category rating scale): sensitivity, 66.2, 86.3, 42.7; specificity, 82.3, 41.9,
      80.0. (3) In groups from Brazil, Chile, and Mexico, respectively, positive
      screening by Definition 1 followed by a clinical examination avoids 499, 213, and
      403 clinical examination per 1000 respondents screened and yields an overall
      prevalence of rheumatic disorder of 30, 43, and 40%. The addition of pain
      intensity (Definition 2) increased the total number of examinations avoided, but
      reduced the prevalence estimate compared to Definition 1 (22.0, 39.0, and 20.0%).
      CONCLUSION: The CCQ appears promising as a screening tool to detect rheumatic
      disorder in Spanish and Portuguese speaking communities in a developing country.
      The findings suggest that the CCQ followed by a full clinical examination in
      positive respondents can provide an acceptable estimate of prevalence of
      rheumatic disorder. The total number of clinical examinations that must be
      administered in population based prevalence surveys can be reduced by using the
      CCQ, while maintaining satisfactory accuracy. Our findings need to be confirmed
      in further applications of the CCQ.

PMID- 9002029
TI  - Characteristics of persons with self-reported arthritis and other rheumatic
      conditions who do not see a doctor.
AB  - OBJECTIVE: To characterize persons with self-reported arthritis and other
      rheumatic conditions who never saw a doctor for their condition. METHODS:
      Comparison of 2 groups (persons who did and did not see a doctor for arthritis)
      identified from cross sectional data from the 1989 National Health Interview
      Survey (NHIS), a stratified random probability sample representative of the US
      civilian noninstitutionalized population. Survey respondents aged 18 years and
      older who answered questions on musculoskeletal conditions and self-reported
      arthritis (n = 2944 unweighted; 36 million weighted) were asked when they last
      saw a doctor for this condition. RESULTS: Of adult Americans who reported
      arthritis, 16.4% reported never seeing a doctor for this problem. This group was
      more often male and younger than those who saw a doctor for arthritis. Persons
      were less likely to see a doctor for arthritis if they had better self-perceived
      health, fewer activity or work limitations due to arthritis, no health insurance,
      and if they were not overweight. Of those who reported never visiting a doctor
      for arthritis, 72.8% reported one or more doctor visits within the preceding 12
      months. Weighted estimates indicate that nearly 6 million Americans with self
      reported arthritis never see a doctor for their condition, including 191,000 with
      activity limitations due to arthritis. About 4.3 million of the 6 million people
      with arthritis reported at least one doctor visit within the previous 12 months.
      CONCLUSION: A "better" health profile and lack of health insurance may explain
      why some people do not see a doctor for arthritis. A substantial number, however,
      have both severe disease as well as health insurance that covers doctor visits
      for other medical problems. These visits represent missed opportunities for early
      diagnosis and effective medical and behavioral intervention.

PMID- 9002030
TI  - Early onset sarcoidosis: not a benign disease.
AB  - There are 2 distinct forms of sarcoidosis in childhood. We describe the clinical
      picture of 6 patients with sarcoidosis of the early onset type. All patients had
      their disease onset during the first 4 years of life. In contrast to the black
      predominance reported in adult patients, our series comprised 5 whites and one
      Latin-American. The triad of rash, arthritis, and uveitis seems to be
      characteristic for this form. The symptoms in our patients were comparable to
      those in the literature. However, a long followup (9-23 yrs) allowed us to
      recognize severe complications of the disease, previously not well known, such as
      blindness (4 patients), growth retardation (3 patients), heart involvement (2
      patients), renal failure (1 patient), and even death in one patient. Pulmonary
      involvement was present only in one patient late in the disease course. This
      condition may be overlooked, and is sometimes misdiagnosed, due to its rarity and
      to its similarities with juvenile arthritis. However, the clinical
      characteristics of the 2 diseases are different. Early and correct diagnosis is
      important in light of the severe disease prognosis, and the possible therapeutic
      options.

PMID- 9002031
TI  - Systemic juvenile rheumatoid arthritis and associated Isaacs' syndrome.
AB  - We describe a patient with systemic onset juvenile chronic arthritis who
      developed clinical and electromyographic features of acquired Isaacs' syndrome.
      This association has not been reported before and possible links between the 2
      diseases are discussed.

PMID- 9002032
TI  - Thrombolysis for acute ischemic stroke in the primary antiphospholipid syndrome.
AB  - Successful intravenous thrombolytic treatment for acute major ischemic stroke was
      given to a 24-year-old woman with primary antiphospholipid syndrome. Our patient
      was a smoker and used oral contraceptives containing estrogen at the time of the
      stroke. We discuss risk factors for stroke and the treatment of arterial
      thrombosis in patients with antiphospholipid antibodies.

PMID- 9002033
TI  - Concurrent gout and Mycobacterium tuberculosis arthritis.
AB  - Concurrent joint infection with Mycobacterium tuberculosis (TB) and demonstration
      of intraarticular monosodium urate (MSU) crystals has not previously been
      reported. We describe a patient with chronic tophaceous gout from whose joints
      both TB and MSU crystals were isolated. We propose a mechanism to explain this
      condition.

PMID- 9002034
TI  - Psoriatic and seronegative inflammatory arthropathy associated with a traumatic
      onset: 4 cases and a review of the literature.
AB  - Although a relationship between psoriatic arthritis or other
      spondyloarthropathies and trauma is discussed in the literature and rheumatology
      textbooks, there are few well documented case reports that substantiate this
      association. We describe 3 patients who developed psoriatic arthritis and a 4th
      who developed unilateral spondyloarthropathy rapidly after trauma. The argument
      that the arthritis in these cases was precipitated by trauma rests upon the
      contiguous sequential temporal relationship between the 2 events and the onset of
      arthritis (and psoriasis) at the sites of trauma.

PMID- 9002035
TI  - Proceedings of the 5th International Workshop on Rheumatoid Arthritis Genetics.
      Manchester, United Kingdom, March 13-15, 1996.

PMID- 9002036
TI  - Problems complicating the genetic epidemiology of rheumatoid arthritis.
AB  - I review problems inherent in considering the genetic epidemiology of rheumatoid
      arthritis (RA). The major area of concern is in case definition, both in
      assigning criteria and in establishing time of onset of disease, since
      presentation fluctuates throughout life. Other problem areas include selection of
      case and controls and the appropriate approach to analysis. Awareness of the
      problems in study design and conduct is fundamental to undertaking valid studies
      in this area.

PMID- 9002037
TI  - Genetic mapping of susceptibility loci in the genes involved in rheumatoid
      arthritis.
AB  - Eighty-nine multicase rheumatoid arthritis families, each containing at least one
      affected sib pair, have been studied for evidence of genetic linkage to a panel
      of 315 microsatellite DNA markers. The families were located through the UK
      national data repository of the Arthritis and Rheumatism Council. Microsatellites
      were genotyped by semiautomated technology using Applied Biosystems sequencers
      (ABI 373). Using the SIBPAIR statistical package, linkage to HLA was confirmed (p
      < 0.0003). Several possible linkages outside HLA were noted, including at least
      one (p < 0.004) that merits further investigation.

PMID- 9002038
TI  - Investigation of candidate disease susceptibility genes in rheumatoid arthritis:
      principles and strategies.
AB  - It has been estimated that a number of non-HLA susceptibility loci exist in
      rheumatoid arthritis (RA), each making relatively small contributions (lambda s <
      2). Previous approaches for whole genome screening are unlikely to be
      sufficiently sensitive to detect such loci. As the pathology of RA already
      indicates several molecules that may be of potential importance in disease
      susceptibility, we propose an alternative approach, targeting candidate genes
      directly. Highly polymorphic dinucleotide markers within a candidate gene
      sequence or close to the gene can be used as markers, and the selection of the
      most appropriate markers is discussed. RA sibling pair families from the
      Arthritis and Rheumatism Council National Repository (n = 200) are used in
      linkage analysis studies. The data generated are analyzed using sib pair analysis
      methods to examine evidence of linkage. The interpretation of such results is
      also discussed, in particular, minimizing the possibility of type I errors, and
      the interpretation of negative results.

PMID- 9002039
TI  - Identification of polygenic disease genes.
AB  - I discuss the identification and cloning of genes involved in determining
      susceptibility to diseases under polygenic control. The process of cloning a
      susceptibility gene is as follows: identification of new genetic markers in the
      region by database analysis, isolation of DNA clones in the region and the
      generation of new genetic markers, refinement of the map position using these
      markers for linkage disequilibrium analysis, construction of a physical and
      disequilibrium map, construction of a clone contig across the critical region in
      yeast artificial chromosomes, PAC, bacterial artificial chromosomes and cosmids,
      and finally gene identification and etiological mutation detection.

PMID- 9002040
TI  - Nonparametric simulation based linkage statistics for general pedigrees.
AB  - A common strategy for testing for linkage without posing a disease model is to
      test for increased marker similarity among the affected pedigree members. We
      developed a simulation based statistic, SimIBD, which measures marker similarity
      in terms of identity-by-descent (IBD) when it can be determined whether or not
      the alleles are IBD, and in terms of the probability of the alleles being IBD
      when it cannot be determined. The SimIBD statistic is not only more powerful than
      its precursor, the affected-pedigree-member (APM) method, but it is also less
      sensitive to the misspecification of marker allele frequencies.

PMID- 9002041
TI  - The sensitivity of different analytical methods to detect disease susceptibility
      genes in rheumatoid arthritis sibling pair families.
AB  - Our aim was to compare the sensitivity of 4 analytical methods to detect linkage
      to a known disease susceptibility locus, HLA-DRB1, in 100 rheumatoid arthritis
      sibling pair families with incomplete parental genotype information. Genotypes
      for the HLA-DRB1 and HLA-A loci were analyzed using (1) identity-by-descent
      (IBD), considering inheritance of maternal and paternal alleles separately; (2)
      maximum likelihood score-IBD (MLS-IBD), which infers missing parental genotypes;
      (3) identity-by-state (IBS), which does not require parental genotypes; and (4)
      transmission disequilibrium test (TDT), which uses affected offspring with a
      heterozygous parent. Due to the small number of informative meoisis for HLA-DRB1,
      the IBD analysis was not significant for linkage (p = 0.014). HLA-A was more
      informative (p = 0.0002). The MLS-IBD method for HLA-DRB1 (p = 0.00004) and HLA-A
      (p < or = 0.00001) was significant. Using IBS both loci gave highly significant
      evidence of linkage, (p < < 0.00001). The TDT detected HLA-DRB1*0401 as the
      allele associated with RA; no HLA-A allele was associated. Thus, sib pair
      families with limited parental genotypes can be used to detect disease
      susceptibility loci, but when selecting the method of analysis the
      informativeness of the markers should be taken into account.

PMID- 9002042
TI  - Analysis of the candidate gene NRAMP1 in the first 61 ARC National Repository
      families for rheumatoid arthritis.
AB  - Maximum likelihood identity-by-descent (IBD) sib pair analysis using a 3 locus
      haplotype NRAMP1-IL8RB-VIL1, or NRAMP1 alone, provided preliminary evidence
      (maximum LOD score = 1.01, p = 0.024) for a gene in this region of human
      chromosome 2q35 contributing to susceptibility to rheumatoid arthritis (RA).
      Candidacy for NRAMP1 as the disease susceptibility gene was supported by a
      significant bias (p < 0.048) toward transmission of the NRAMP1 promoter region
      allele 3 in affected offspring.

PMID- 9002043
TI  - Corticotropin releasing hormone promoter region polymorphisms in rheumatoid
      arthritis.
AB  - The regulation of the human corticotropin releasing hormone (CRH) gene is of
      interest since it mediates the interaction of stress events and inflammatory
      signals on the hypothalamo-pituitary-adrenal axis. Patients with rheumatoid
      arthritis (RA) have impaired CRH response to stress so that polymorphisms in the
      5' regulatory region of the CRH gene could be responsible for decreased CRH
      responsiveness. To examine whether patients with RA have polymorphisms of the
      regulatory region of CRH, we amplified fragments of the 3.7 kb genomic DNA from 5
      unrelated patients with RA and 2 controls. DNA sequencing revealed 3 nucleotide
      variants. These variants have been characterized as a T-->C base substitution
      located at position 1273 (alleles A1 and A2) and at position 2942 (alleles B1 and
      B2), and a C-->G base substitution located at position 95 (alleles C1 and C2),
      respectively, of the Genbank entry x67661. These substitutions lead to the
      destruction of the recognition site for AflIII (position 1273) and CviJI
      (position 95), and an introduction of a recognition site for BsmAI (position
      2942) restriction enzymes, respectively. Three of 5 patients with RA were
      heterozygous for all 3 polymorphisms observed, while the 2 polymorphisms at
      positions 1273 and 2942 were represented in one control only. Post polymerase
      chain reaction (PCR) restriction fragment length polymorphism was performed to
      investigate the frequency of the polymorphisms in 99 healthy unrelated Caucasians
      and 28 members of CEPH (Centre d'Etudes du Polymorphisme Humaine) families. The
      AflIII, BsmAI, and CviJI polymorphisms cosegregate absolutely in both the
      controls and the CEPH families. The frequency for allele 1 was 0.869, while that
      for allele 2 was 0.131, with the following observed genotype frequencies: A1/A1
      0.75; A1/A2 0.23; A2/A2 0.02. The T-->C base substitution at position 2942 leads
      to destruction of a consensus sequence for transcription factor GH-CSE2. These
      novel polymorphisms should therefore be considered in studies of CRH gene
      expression and may play a role in the pathogenesis of RA.

PMID- 9002044
TI  - Tumor necrosis factor microsatellite haplotypes are different in male and female
      patients with RA.
AB  - We investigated whether tumor necrosis factor (TNF) microsatellite polymorphisms
      are associated with sex and age at disease onset in rheumatoid arthritis (RA). A
      case-control study was used to compare the frequencies of TNF microsatellite
      alleles in 181 Caucasian RA cases and 251 controls. TNF microsatellite genotyping
      was performed using fluorescent based polymerase chain reaction (PCR) techniques
      and HLA-DR typing using PCR based sequence specific oligonucleotide probing. The
      association of TNF microsatellite alleles a6, b5, and d4 with RA was confirmed.
      These polymorphisms were more frequent in female patients. Male patients with RA
      with young age at onset had a different TNF microsatellite profile, TNFa2, b1,
      and c2 being the most frequent. TNF microsatellite polymorphisms are different in
      male and female patients with RA. This difference was more obvious in patients
      stratified according to age at onset. Sex and age at onset should be considered
      in studies of genetic factors in RA.

PMID- 9002045
TI  - Mapping of 10 novel microsatellites in the MHC class III region: application to
      the study of autoimmune disease.
AB  - The MHC class III region contains many genes that are good candidates for
      involvement in autoimmune disease. We report the mapping and characterization of
      10 novel (CA)n microsatellites spanning the region, which are highly informative
      and suitable for linkage and association studies. We used these markers to
      identify haplotypes of MHC class III microsatellite alleles in DNA from cell
      lines homozygous for MHC class II and class I alleles.

PMID- 9002046
TI  - Interaction between genes in the T cell receptor-alpha locus and HLA-DR4 in
      rheumatoid arthritis susceptibility.

PMID- 9002047
TI  - Qualitative and quantitative analysis of HLA-DRB gene expression.
AB  - Determination of the molecular mechanisms influencing HLA-DRB gene expression
      would allow better understanding of the regulation of the immune response in
      normal as well as in pathological conditions. We started an extensive sequencing
      analysis of the proximal promoter regions of the DRB genes and observed a
      nucleotide polymorphism involving the classical regulatory regions of the DRB
      promoters. These nucleotide substitutions were observed to induce variations of
      the promoter activities as assessed by chloramphenicol acetyl transferase assays
      and the quantification of DRB transcripts. Similar analysis performed in patients
      with rheumatoid arthritis strongly suggests dysregulation of HLA-DRB gene
      expression.

PMID- 9002048
TI  - Influence of the QKRAA/QRRAA/RRRAA motifs of the third hypervariable region of
      HLA-DRB1 in the development of rheumatoid arthritis.
AB  - Most patients with rheumatoid arthritis (RA) express HLA-DR4, HLA-DR1, or HLA
      DR10. The DRB1 chains of these alleles have highly homologous 3rd hypervariable
      regions, with the motifs QKRAA, QRRAA, or RRRAA. The role played by the QKRAA,
      QRRAA, and RRRAA motifs in the development of RA is unknown. It may involve
      interaction with a T cell, an antigenic peptide, or an unknown ligand. We
      investigated the role played by the QKRAA motif and observed that it was
      expressed on numerous proteins from bacteria and viruses. However, we detected no
      anti-QKRAA autoimmunization in patients with RA. We found that QKRAA is a binding
      motif for bacterial and human 70 kDa heat shock proteins, and suggest that this
      may explain both its being expressed on so many proteins and its role in the
      development of RA.

PMID- 9002049
TI  - Fibromyalgia and disability.

PMID- 9002050
TI  - Fibromyalgia and disability.

PMID- 9002051
TI  - Fibromyalgia and disability.

PMID- 9002052
TI  - Low serum creatine kinase activity in rheumatoid arthritis.

PMID- 9002054
TI  - Effective splenectomy in agranulocytosis associated with systemic lupus
      erythematosus.

PMID- 9002053
TI  - Association of DPB1 genes with systemic lupus erythematosus.

PMID- 9002055
TI  - Resolution of calcium deposits after therapeutic ultrasound of the shoulder.

PMID- 9002056
TI  - Hypopituitarism with empty sella after steroid pulse therapy.

PMID- 9002057
TI  - What is the risk of Achilles tendon rupture with ciprofloxacin?

PMID- 9002059
TI  - The whiplash (hyperextension-flexion) syndrome: a disorder of dorsal root
      ganglion neurons?

PMID- 9002058
TI  - Periarticular ankle sarcoidosis: a variant of Lofgren's syndrome.

PMID- 9002060
TI  - New assessment techniques for evaluation of posttraumatic spinal cord function in
      the rat.
AB  - To evaluate new pharmacologic agents with potentially beneficial effects on
      posttraumatic spinal cord function, we used a modified weight drop (WD) technique
      to induce spinal cord injuries. These contusive spinal cord injuries in the rat
      closely mimic the human clinicopathologic situation. Especially for drug
      screening purposes, the moderate and mild injuries are of interest, as both the
      beneficial and potentially harmful effects of experimental treatment can be
      detected. In this study, we describe two new functional tests that were
      particularly designed to detect small differences in spinal cord function after
      moderate and mild injuries. First, for examination of locomotion, a computer
      analysis of the thoracolumbar height (TLH) was designed. Second, for
      investigation of the conduction properties of the injured rat spinal cord, we
      measured rubrospinal motor evoked potentials (MEP). The efficacy of the new
      assessment techniques to monitor spinal cord function was compared to Tarlov
      scores and to morphometric analysis of preserved white matter at the injury site.
      The results of this study indicated that for behavioral analysis, TLH
      measurements as compared with Tarlov rating appeared to be more sensitive for
      exact and objective discrimination between small differences in motor function.
      Amplitudes of the rubrospinal MEP, but not latencies or the number of peaks,
      proved to be most sensitive to determine subtle differences in posttraumatic
      spinal cord function. A significant linear correlation was found between TLH and
      amplitude of the rubrospinal MEP. We conclude that for objective assessment of
      the spinal cord after moderate and mild contusive injury, TLH and rubrospinal MEP
      amplitudes are very valuable measures to demonstrate small functional
      differences.

PMID- 9002061
TI  - Operant conditioning of H-reflex in spinal cord-injured rats.
AB  - Operant conditioning of the spinal stretch reflex or its electrical analog, the H
      reflex, is a new model for exploring the mechanisms of supraspinal control over
      spinal cord function. Both rats and primates can gradually increase (HRup
      conditioning mode) or decrease (HRdown conditioning mode) soleus H-reflex
      magnitude when exposed to an operant conditioning task. This study used H-reflex
      operant conditioning to assess and modify spinal cord function after injury.
      Soleus H-reflexes were elicited and recorded with chronically implanted
      electrodes from rats that had been subjected to calibrated contusion injuries to
      the spinal cord at T8. From 18 to 140 days after injury, background EMG, M
      response amplitude, and initial H-reflex amplitude were not significantly
      different from those of normal rats. HRdown conditioning was successful in some,
      but not all, spinal cord-injured rats. The H-reflex decrease achieved by
      conditioning was inversely correlated with the severity of the injury as assessed
      histologically or by time to return of bladder function. It was not correlated
      with the length of time between injury and the beginning of conditioning. The
      results confirm the importance of descending control from supraspinal structures
      in mediating operantly conditioned change in H-reflex amplitude. In conjunction
      with recent human studies, they suggest that H-reflex conditioning could provide
      a sensitive new means for assessing spinal cord function after injury, and might
      also provide a method for initiating and guiding functional rehabilitation.

PMID- 9002062
TI  - Riluzole, a novel neuroprotective agent, attenuates both neurologic motor and
      cognitive dysfunction following experimental brain injury in the rat.
AB  - Several potential mechanisms are involved in mediating the pathophysiology of
      traumatic brain injury (TBI), including inflammatory processes and
      excitotoxicity. In the present study, we evaluated the ability of the use
      dependent sodium channel inhibitor Riluzole to attenuate cognitive and neurologic
      motor deficits and reduce regional cerebral edema and histologic cell damage
      following lateral fluid-percussion (FP) brain injury in rats (n = 109). In study
      1, 58 anesthetized male Sprague-Dawley rats (350-400 g) were subjected to FP
      brain injury of moderate severity (2.3-2.5 atm). Fifteen minutes following brain
      injury, animals randomly received an i.v. bolus of either Riluzole (4 mg/kg, n =
      11), Riluzole (8 mg/kg, n = 11), or glycol vehicle (n = 20), followed by 6 h and
      24 h s.c. injections (identical dose). Surgically prepared but uninjured animals
      received vehicle (n = 16) and served as controls. Animals were evaluated for
      cognitive deficits at 48 h postinjury and killed for assessment of regional brain
      edema. Administration of vehicle or Riluzole (4 mg/kg x 3) had no significant
      effect on memory or edema, whereas Riluzole (8 mg/kg x 3) significantly
      attenuated post-traumatic cognitive dysfunction (p < 0.05). In study 2, a second
      group of animals (n = 25) was injured, treated with Riluzole (8 mg/kg x 3 doses,
      n = 13) or vehicle (n = 12), and evaluated for neurologic motor function over 2
      weeks. Animals treated with Riluzole demonstrated significantly improved motor
      scores beginning 1 week postinjury (p < 0.05). In study 3, brain-injured animals
      were treated with Riluzole (8 mg/kg x 3 doses, n = 10) or vehicle (n = 10), and
      posttraumatic lesion volume was assessed at 48 h postinjury using 2,3,5
      triphenyltetrazolium chloride (TTC) staining. Treatment with Riluzole had no
      significant effect on posttraumatic lesion volume. The present study demonstrates
      that use-dependent sodium channel inhibitors, such as Riluzole, can attenuate
      both cognitive and neuromotor dysfunction associated with brain trauma.

PMID- 9002063
TI  - Regional generation of leukotriene C4 after experimental brain injury in
      anesthetized rats.
AB  - Regional concentrations of leukotriene C4 and extravasation of Evans blue were
      measured after lateral fluid-percussion brain injury in rats. Tissue levels of
      LTC4 were elevated in the injured cortex at 10 min, 30 min, and 1 h after injury;
      these levels returned to normal by 2 h after injury. Increases in the levels of
      LTC4 were also observed in the ipsilateral hippocampus after brain injury, and
      these elevations persisted for 2 h after injury. No significant increase in
      levels of LTC4 was observed in the contralateral cortex at any time after injury.
      A substantial extravasation of Evans blue was observed only in the ipsilateral
      cortex and hippocampus at 3 h and 6 h after brain injury. Although a temporal
      association between LTC4 and blood-brain barrier (BBB) breakdown is suggested by
      these data, no cause-and-effect relationship has been addressed in this study.
      However, it is possible that, as is true for cerebral ischemia, LTC4 may play a
      role as a mediator in the BBB breakdown associated with fluid-percussion brain
      injury in rats.

PMID- 9002064
TI  - MK-801 reduces retinal ganglion cell survival but improves visual performance
      after controlled optic nerve crush.
AB  - Excitotoxicity is implicated in secondary cell death after ischemic or traumatic
      brain injury. We therefore evaluated the role of excitotoxicity mediated by the
      NMDA glutamate receptor subtype on retinal ganglion cell (RGC) survival and
      visual performance after optic nerve injury in adult rats. To monitor visual
      deficits after mild optic nerve crush, rats were trained in a two-choice pattern
      discrimination task. Immediately after the crush and on postoperative day 1, MK
      801 (1 nmol), a noncompetitive open channel blocker of the NMDA-receptor, was
      injected intraocularly. Within the first few days after crush, all rats showed a
      loss of their discrimination ability that was followed by a significant recovery
      within a 3-week testing period. Although animals treated with MK-801 had a
      significantly smaller initial deficit compared with PBS-injected controls,
      anatomic investigations using retrograde HRP tracing revealed a significant
      retrograde loss of RGC in lesioned rats that was significantly exacerbated by MK
      801. These results confirm our earlier studies suggesting that neuronal damage
      does not uniformly match behavioral defects in CNS injury paradigms and that near
      normal visual performance occurs in rats with only about 10% of RGC being
      connected to their target. The observation that after traumatic injury MK-801 is
      neuroprotective functionally while being neurotoxic anatomically is a structural
      functional paradox that needs to be explored further.

PMID- 9002065
TI  - Intercellular adhesion molecule-1 expression on glia following brain injury:
      participation of interleukin-1 beta.
AB  - Interleukin-1 (IL-1), one of the most important inflammatory cytokines, promotes
      glia to express intercellular adhesion molecule-1 (ICAM-1) in vitro. IL-1 is
      known to be produced in situ immediately after brain insults and recently we have
      found that glia, including astrocytes, express ICAM-1 in vivo following cortical
      stab wounds. To evaluate the participation of IL-1 beta in posttraumatic ICAM-1
      expression on glia in vivo, we performed the following experiments. A cortical
      stab wound was made in the brain of a mouse. ICAM-1-immunopositive glia began to
      emerge around the wound from 6 h postlesioning. The number of cells reached a
      maximum at 48 h and persisted until 7 days postlesioning. Next, a neutralizing
      monoclonal antibody against IL-1 beta was infused into the wound immediately
      following the injury. This treatment resulted in a significant reduction of ICAM
      1-positive glia at 24 and 48 h postlesioning. We conclude, therefore, that IL-1
      beta affects ICAM-1 expression on glia in vivo after experimental brain injury
      and presumably plays an important role in brain wound repair.

PMID- 9002066
TI  - The role of excitatory amino acids in hypothermic injury to mammalian spinal cord
      neurons.
AB  - Hypothermia has been reported to be beneficial in CNS physical injury and
      ischemia. We previously reported that posttraumatic cooling to 17 degrees C for 2
      h increased survival of mouse spinal cord (SC) neurons subjected to physical
      injury (dendrite transection) but that cooling below 17 degrees C caused a lethal
      NMDA receptor-linked stress to both lesioned and uninjured neurons. The present
      study tested whether cooling below 17 degrees C increases extracellular levels of
      excitatory amino acids (EAA). SC cultures were placed at 10 degrees C or 37
      degrees C. Glutamate (Glu) and aspartate (Asp) levels were higher in the medium
      of the cooled cultures after 0.5 h (23 +/- 4 nM/microgram vs. 4 +/- 1
      nM/microgram and 4 +/- 1 nM/microgram vs. 1 +/- 0 nM/microgram, respectively).
      The concentration of each EAA then declined and reached a plateau at 2-4 h that
      was still significantly higher than control levels (p < 0.0001, two-factor ANOVA,
      three cultures per group). Other amino acids (glycine, asparagine, glutamine,
      serine) showed an opposite pattern, with higher levels in the 37 degrees C group.
      Both NMDA and non-NMDA antagonists prevented the lethal cold injury. Survival of
      SC neurons cooled at 10 degrees C for 2 h and rewarmed for 22 h was 58% +/- 25%
      in the control group, 94% +/- 5% in the CNQX-treated group, 97% +/- 5% in the
      DAPV-treated group, and 99% +/- 2% in the group treated with both antagonists [p
      < 0.0006, one factor ANOVA, five cultures (> 120 neurons) per group]. These
      results show that death of neurons cooled to 10 degrees C is caused by elevated
      extracellular Glu and Asp and requires activation of both the NMDA and non-NMDA
      receptor subtypes.

PMID- 9002067
TI  - Differentiation between vaccine-related and wild-type polioviruses using a
      heteroduplex mobility assay.
AB  - A heteroduplex mobility assay (HMA) was developed for intratypic differentiation
      between poliovirus isolates. The assay is based on polymerase chain reaction
      (PCR) amplification of a 480 base pair fragment which encodes a variable segment
      of VP1, followed by denaturation and reannealing of the resulting single strands
      with those from reference Sabin targets. Mismatches between wild-type and Sabin
      vaccine templates result in the formation of detectable heteroduplexes of reduced
      electrophoretic mobility. Poliovirus strains confirmed previously as wild-type or
      vaccine-like by PCR and sequencing were all correctly identified using the HMA.
      Mixtures of both wild-type and vaccine-like strains in a single isolate could
      also be detected using this technique. The results of this study demonstrate that
      heteroduplex analysis is a simple, rapid, and sensitive means for differentiating
      between vaccine-like and wild-type poliovirus isolates.

PMID- 9002069
TI  - Analytical and laboratory evaluation of a new fully-automated third generation
      enzyme immunoassay for the detection of antibodies to the hepatitis C virus.
AB  - An analytical and laboratory evaluation of a newly-developed fully-automated
      third generation ELISA for the detection of anti-HCV (Cobas Core Anti-HCV EIA,
      Roche) was undertaken. Coefficients of variation (CVs) calculated on positive
      control and serum samples ranged from 5.9 to 9.8% in the intra-assay precision
      test and from 3.9 to 11.3% in the inter-assay evaluation. With regard to the
      study of clinical laboratory performance, five groups of sera pre-screened with
      two third generation ELISA (Ortho HCV 3.0 ELISA; Innotest HCV Ab III) were
      assayed: anti-HCV negative samples (n = 932); anti-HCV positive samples (n =
      449); difficult sera of different origin (n = 113); sera with discrepant results
      in the two ELISAs (n = 50); sera with an indeterminate result in one or more
      confirmatory test (n = 34). The overall concordance between the Roche anti-HCV
      EIA and the two reference assays was 97.5 and 97.8% for the Ortho and for the
      Innogenetics assays, respectively. Although it is not possible to provide
      absolute figures for clinical sensitivity and specificity, the results of the
      study on discrepant samples show that the Cobas Core Anti-HCV gives a number of
      negative results with positive or indeterminate confirmatory anti-HCV tests,
      which is intermediate between the Ortho and the Innogenetics assay. In contrast,
      only 5% Cobas Core Anti-HCV reactive sera are not positive or clear-cut single
      band reactive by supplemental assays. The results show that the new fully
      automated third generation anti-HCV test is a valid alternative to other
      commercially available assays for screening of antibodies to the hepatitis C
      virus.

PMID- 9002068
TI  - Evaluation and comparison of PCR and hybridization methods for rapid detection of
      cytomegalovirus in clinical samples.
AB  - Rapid diagnosis of cytomegalovirus (CMV) infection may be obtained by molecular
      techniques, such as the polymerase chain reaction (PCR) and hybridization assays.
      The optimal technique to detect CMV in clinical samples was assessed. Two
      different PCR assays were used, targeting either the major immediate early 1 (MIE
      1) or the HXLF 4 gene. The PCR products were detected by gel electrophoresis, dot
      blotting and an easy to use, rapid, solid phase hybridization assay, DNA enzyme
      immunoassay (DEIA). Standard tissue culture was also used. Cerebrospinal fluids
      (18), liver biopsies (9) from hepatic transplant recipients, amniotic fluids (7)
      from mothers with suspected peripartum infection, and samples (6) of
      miscellaneous origin (brain and fundus biopsy, pericardial and pleural fluid)
      were tested. Among the 40 samples, CMV was detected in 19 cases. Three were
      positive by both molecular techniques and tissue culture, 14 by molecular methods
      and 2 by culture. 16/19 or 9/19 CMV-positive samples were detected by PCR
      amplification of the HXLF 4 or MIE 1 gene, respectively and 14/16 HXLF 4-positive
      samples were detected using either dot-blot or DEIA, compared to 9/16 using gel
      electrophoresis. Thus, the most sensitive assays for the detection of CMV in
      clinical samples using the methods compared in the current study were PCR
      amplification of the HXLF 4 gene followed by dot-blot or DEIA hybridization.

PMID- 9002070
TI  - Comparison of three different hybridization assays in the quantitative
      measurement of serum hepatitis B virus DNA.
AB  - The measurement of hepatitis B virus (HBV) DNA, is important for monitoring and
      evaluating the efficacy of anti-viral agents in the treatment of patients with
      chronic hepatitis B. Three different hybridization assays for quantitative
      measurement of HBV DNA: direct membrane (dot-blot) hybridization, liquid
      hybridization (Abbott HBV DNA assay) and branched DNA signal amplification assay
      (Quantiplex, Chiron), were applied to 114 serial serum samples obtained from 13
      patients with chronic active hepatitis B who had received ribavirin 600 mg daily
      for four weeks. Among the three assays, the correlation was found to be highest
      between Quantiplex and Abbott HBV DNA assay (r = 0.71, p < 0.01), moderate
      between Quantiplex and dot-blot hybridization (r = 0.58, p < 0.01) and lowest
      between dot-blot hybridization and Abbott HBV DNA assay (r = 0.27, p < 0.01).
      Quantiplex detected 107 (94%) of 114 specimens and was the most sensitive assay.
      All specimens positive by dot-blot hybridization and Abbott HBV DNA assays were
      detected positive by Quantiplex. The Dot-blot hybridization assay detected all 89
      (100%) specimens with a high HBV DNA level (> or = 10 million genome equivalent
      (Meq)/ml by Quantiplex), but detected only 7 (50%) of 14 specimens with a low HBV
      DNA level (< 10 Meq/ml). The Abbott HBV DNA assay detected 85 (95%) of 89
      specimens with a high HBV DNA level, but detected only 3 (17%) of 18 specimens
      with a low HBV DNA level. Among 7 negative specimens in the Quantiplex assay, 2
      were detected positive by polymerase chain reaction. In conclusion, Quantiplex
      assay was more sensitive than Abbott HBV DNA assay and dot-blot hybridization
      assay for quantitative measurement of serum HBV DNA and can be used in the
      evaluation of the therapeutic drug effect on chronic hepatitis B patients.

PMID- 9002071
TI  - Nested PCR assays with novel primers yield greater sensitivity to Tanzanian HIV-1
      samples than a commercial PCR detection kit.
AB  - To investigate the efficacy of the SK431/SK145 primer pair and two nested primer
      assays in amplifying African HIV-1 samples, a total of 35 Tanzanian PBMC samples
      were examined. These were assayed by two HIV-1 specific nested in-house PCR
      assays and a commercial HIV-1 PCR kit (GeneAmp) using SK431/SK145 as the primer
      pair. One of the nested PCR assays has been evaluated previously (old assay),
      whereas the modified assay was constructed from the HIV-1 sequence alignment
      released in August 1993. The modified nested primer assay showed increased
      sensitivity in the gag and env regions compared to the old nested primer assay.
      However, both the old and the modified nested primer assays displayed higher
      sensitivity for the detection of Tanzanian HIV-1 proviruses than the GeneAmp
      assay. When two regions were used (gag and env) as targets for the amplification,
      the modified nested primer assay detected 97.1% (34/35) of the proteinase K lysed
      samples, compared to 68.6% (24/35) using the SK431/SK145 primer pair (P <
      0.01**). The results indicate that the SK431/SK145 primer pair may be less
      suitable when HIV-1 samples from Africa are analysed. The results also show that
      continuous modification of primer sequences can improve and maintain high
      sensitivity for the detection of highly divergent HIV-1 strains.

PMID- 9002073
TI  - Improved method for counting virus and virus like particles.
AB  - An improved method for counting virus and virus like particles by electron
      microscopy (EM) was developed. The procedure involves the determination of the
      absolute concentration of pure or semi-pure particles once deposited evenly on EM
      grids using either centrifugation or antibody capture techniques. The counting of
      particles was done with a Microfiche unit which enlarged approximately 50 x the
      image of particles on a developed negative film which had been taken at a
      relatively low magnification (2500 x) by EM. Initially, latex particles of a
      known concentration were counted using this approach, to prove the accuracy of
      the technique. The latex particles were deposited evenly on an EM grid using
      centrifugation (Modified Beckmen EM-90 Airfuge technique). Subsequently,
      recombinant Bluetongue virus (BTV) core-like particles (CLPs) captured by a
      Monoclonal antibody using a novel sample loading method were counted by the
      Microfiche unit method and by a direct EM method. Comparison of the simplified
      counting method developed with a conventional method, showed good agreement. The
      method is simple, accurate, rapid, and reproducible when used with either pure
      particles or with particles from crude cell culture extracts.

PMID- 9002072
TI  - Evaluation of monoclonal antibodies for generic detection of flaviviruses by
      ELISA.
AB  - Three monoclonal antibodies (Mabs) specific for the envelope (E) protein of
      flaviviruses were evaluated for use in an antigen capture ELISA. Three
      combinations of Mabs and a combination of polyclonal antibodies (Pabs) were
      evaluated in antigen capture ELISAs for their ability to detect 18 flaviviruses.
      The Mab ELISAs detected 50% of flavivirus antigens with a sensitivity between 1
      and 9 x 10(4)/ng viral protein/ml, however, none of the ELISAs evaluated proved
      to be useful for generic detection of flaviviruses, being unable to detect tick
      borne flaviviruses and some mosquito-borne flaviviruses. The inability of the
      ELISAs to detect tick-borne flaviviruses is thought to be due to the conformation
      of surface epitopes, which the Mabs were unable to recognise. This was again
      observed using recombinant TBE virus prM/E protein as antigen in direct and
      antigen capture ELISAs. The Mabs reacted with the prM/E protein when it was
      denatured by binding directly onto the solid phase, but the antibodies were
      unable to detect the native protein in antigen capture ELISAs. The antigen
      capture ELISAs evaluated in this study were considered to be unsuitable for the
      generic detection of flaviviruses, but may provide a sensitive diagnostic assay
      for specific flavivirus infection.

PMID- 9002074
TI  - Competitive reverse transcription-polymerase chain reaction for quantifying
      murine AIDS virus.
AB  - The causative agent of murine AIDS (MAIDS) is the defective murine leukemia virus
      BM5d, that requires the replication-competent ecotropic MuLV (BM5e) helper virus.
      We developed a competitive quantitative PCR method including specific internal
      standards to quantify the expression of BM5d in the spleen of infected mice and
      to characterize BM5d expression kinetics following experimental infection.
      Specimen RNA was reverse-transcribed and co-amplified with a competitive template
      containing a gag sequence specific for BM5d that can be discriminated from that
      corresponding to wild-type cDNA by the presence of a unique restriction site,
      Bg/II. PCR products were quantified by means of densitometric analysis after
      ethidium bromide staining of gels. To standardise the RNA extraction and reverse
      transcription steps, the amount of defective-virus mRNA was compared to a
      constant copy number of murine beta actin mRNA. LP-BM5 production was measured in
      the spleen of infected mice. Defective gag mRNA production was compared to that
      of the ecotropic virus. The mRNA level of the defective virus and the titre of
      replicative virus increased with the duration of infection, and the amount of
      defective virus mRNA correlated with the titre of replicating virus.

PMID- 9002076
TI  - Method for concentrating and purifying recombinant autonomous parvovirus vectors
      designed for tumour-cell-targeted gene therapy.
AB  - Recent work has highlighted the use of parvoviruses as potential vectors for
      tumour-cell-targeted gene therapy. The oncotropic properties of the prototype
      strain of minute virus of mice (MVMp) suggest that this virus might be a useful
      vehicle for introducing selectively therapeutic genes, e.g. lymphokine or suicide
      genes, into tumour cells and preferentially expressing them. But the low titre of
      recombinant virus stocks (10(5)-10(6) infectious units per ml) and their high
      level of contamination by cell proteins make it practically impossible to
      evaluate their efficacy in in vivo systems. A technique is described for
      producing cellular contaminant-free stocks of recombinant virus particles, with
      titres up to 5 x 10(8) IU/ml.

PMID- 9002075
TI  - Isolation of viruses from clinical specimens in microtitre plates with cells
      inoculated in suspension.
AB  - Virus isolation is essential for the provision of a full diagnostic virology
      service. Present methods are time consuming, expensive and relatively inflexible
      for routine use. Our objective was to audit our existing virus isolation system
      and to develop a sensitive, flexible virus isolation system which could be
      adapted for use in a busy routine laboratory which is required to provide a
      service for a wide range of clinical situations. We carried out a pilot study
      which compared conventional roller tube monolayer cultures to a microplate system
      using cells inoculated in suspension and showed that the microplate method using
      extra cell lines could provide a more sensitive system for virus isolation. This
      system was adapted for routine use using six cell lines inoculated in suspension
      and the results are presented for 2610 specimens for virus isolation and 972 for
      Clostridium difficile toxin (CDT) detection. There were 516 viruses isolated and
      229 specimens positive for CDT using this system. Polioviruses (92), echoviruses
      (35), coxsackieviruses (15) and untyped enteroviruses (13) were isolated in RMK,
      E6-vero and RD cells. Adenoviruses (137) were isolated in HEp2 and E6-vero cells.
      Herpes simplex virus (HSV) was isolated from 149 specimens in E6-vero, FCL and
      HFF9 cells. Myxoviruses (38) and paramyxoviruses were isolated in RMK cells. HEp2
      was the only cell line necessary to isolate the 33 respiratory syncytial viruses
      (RSV). Cytomegaloviruses (CMV) (2) and varicella zoster (1) virus (VZV) were
      isolated only in the human fibroblast cell line HFF9. Rubella virus was isolated
      from a baby with congenital rubella in RMK, E6-vero and additionally in BGM
      cells. In conclusion, the use of cells inoculated in suspension in microtitre
      plates for virus isolation was sensitive and convenient. It allowed the use of
      six cell lines for routine virus isolation without using additional laboratory
      staff time. It improved turnaround times. It was also safer microbiologically
      than conventional isolation in tube monolayers. The precise identification of
      virus isolates was simplified.

PMID- 9002077
TI  - Clinical practice guidelines in nutrition support: can they be based on
      randomized clinical trials?
AB  - As rationing of health care services becomes an increasing reality, the pressure
      to justify interventions such as nutrition support will intensify. The
      establishment of clinical practice guidelines is one means of providing
      practitioners with such justification, but clinical practice guidelines for
      nutrition support cannot be based primarily on prospective randomized trials.
      This situation arises as the result of limitations specific to nutrition support
      whereby the most malnourished patients-those who appear most likely to show a
      benefit from the treatment-cannot be randomized to a no feeding group and are
      therefore excluded from participation in the study. As the result of this
      limitation, marginal candidates for nutrition support have been included in some
      trials, potentially masking the benefits of this treatment. An additional problem
      limiting present interpretation of published reports of randomized trials in
      nutrition support is the fact that ongoing research continues to yield
      improvements in the clinical practice of nutrition support. Thus the nutrition
      support group in such trials may not have received this treatment according to
      current practice. The A.S.P.E.N. Guidelines, based on both randomized prospective
      trials and other types of evidence, represent an important contribution to the
      practice of nutrition support. Testing of the performance of these and other
      guidelines in clinical practice and further outcomes research will be important
      steps toward revision and improvement of nutrition support, but may be difficult
      to achieve in the near future.

PMID- 9002078
TI  - Gastrointestinal, hepatic, and metabolic effects of enteral and parenteral
      nutrition in rats infused with tumor necrosis factor.
AB  - BACKGROUND: We previously showed that continuous infusion of tumor necrosis
      factor-alpha (TNF-alpha) in orally fed rats caused weight and muscle wasting
      mainly because of anorexia. However, when we tried to prevent weight loss by
      giving total parenteral nutrition (TPN), TNF-infused rats developed
      hyperglycemia, azotemia, and hepatic abnormalities. The present study was
      designed to determine whether the enteral (ENT) feeding resulted in fewer
      complications than parenteral (TPN) feeding in TNF-infused rats (100
      micrograms/kg/d). METHODS: Forty-two rats were randomly allocated to four groups
      as follows: controls: TPN and ENT, and TNF-infused: TPN + TNF and ENT + TNF. All
      groups received the same liquid defined formula diet either enterally or
      parenterally (isocaloric and isonitrogenous). Twenty-six rats were used for
      studies of body composition and metabolism and 16 for vascular permeability.
      RESULTS: TPN + TNF and ENT + TNF rats showed significantly increased liver
      weights and significantly reduced carcass weights compared with controls. A
      significant reduction in the muscle weights and total protein, as well as
      hyperglycemia, azotemia, and abnormal liver enzymes was also seen in ENT + TNF
      rats compared with ENT rats. The gastric and small intestinal mucosa was inflamed
      in the ENT + TNF but not in the ENT, TPN + TNF, and TPN rats. The plasma TNF
      levels determined by bioassay were significantly increased in the TPN + TNF and
      ENT + TNF rats compared with controls. There was increased vascular permeability
      in the stomach and small and large intestine in the ENT + TNF rats compared with
      ENT rats. No significant changes in vascular permeability were seen in TPN and
      TPN + TNF rats. CONCLUSIONS: ENT, but not TPN, resulted in prominent changes in
      the body composition and marked metabolic effects in the TNF-infused rats.

PMID- 9002080
TI  - Efficacy of different triglycerides in total parenteral nutrition for preventing
      atrophy of the gut in traumatized rats.
AB  - BACKGROUND: The efficacy of different fat emulsions as components of a total
      parenteral nutrition (TPN) regimen on the integrity of the gut was assessed in
      traumatized rats. With the release of the short-chain fatty acids butyric or
      propionic acid during the hydrolysis of a structured triglyceride containing
      butyric acid (C4-L-C4-TG) or the beta-oxidation of nonanoic acid from trinonanoin
      (C9TG), respectively, the infusion of these two triglycerides was supposed to
      reveal positive effects against the TPN-induced atrophy of the intestine.
      METHODS: After 3 days of fiber-free liquid diet, rats were traumatized
      (laparotomy) and catheterized. Afterwards they received equicaloric TPN that
      delivered 1008 kJ (241 kcal)/kg of body weight per day and 30% nonprotein
      calories as fat emulsion. The four fat emulsions tested in four groups of six
      animals contained either long-chain triglycerides (LCT), medium-chain
      triglycerides (MCT)-LCT (1:1), C9TG/LCT (1:1) or C4-L-C4-TG. Animals of a control
      group were infused with isovolemic 0.9% NaCl solution and were offered oral
      standard chow. RESULTS: After 7 days of MCT/LCT administration, the mass-to
      length ratio of the total small bowel as well as the masses of mucosa/submucosa
      and muscularis/serosa in 10-cm segments of the distal half of the small bowel
      were significantly higher than that found in the other TPN groups or not
      different from controls. Histometric measurement of the villus height in the
      ileum revealed no statistically significant differences from controls for the
      rats of the MCT/LCT and C4-L-C4-TG groups. In the colon, no statistically
      significant differences between TPN groups were found for either parameter.
      CONCLUSIONS: Within the tested fatty substrates the MCT/LCT fat emulsion revealed
      less structural impairments in the distal half of the small bowel regarding
      mucosa/submucosa (mass and villus height), but also muscularis/ serosa (mass).

PMID- 9002079
TI  - Comparison of the safety of early enteral vs parenteral nutrition in mild acute
      pancreatitis.
AB  - BACKGROUND: This prospective study was designed to compare the safety, efficacy,
      cost, and impact on patient outcome of early total enteral nutrition (TEN) vs
      total parenteral nutrition (TPN) in acute pancreatitis. METHODS: Patients
      admitted with acute pancreatitis or an acute flare of chronic pancreatitis,
      characterized by abdominal pain and elevated serum amylase and lipase, were
      randomized to receive either isocaloric and isonitrogenous TEN (via a nasojejunal
      feeding tube placed endoscopically) or TPN (via a central or peripheral line)
      started within 48 hours of admission. RESULTS: Thirty patients were studied over
      32 admissions (TEN given on 16 and TPN on 16) for acute pancreatitis. There were
      no differences on admission in mean age, Ranson criteria, multiple organ failure
      score (MOF), or APACHE III score between TEN and TPN groups. Although slower to
      approach goal feeding over the first 72 hours of admission, TEN patients received
      71.3% goal calories by day 4 vs 85.2% for TPN patients (not significant). There
      were no deaths and no differences between groups in serial pain scores, days to
      normalization of amylase, days to diet by mouth, serum albumin levels, or percent
      nosocomial infection. However, the mean cost of TPN per patient was over four
      times greater than that for TEN ($3294 vs $761, respectively, p < .001). Mean
      serial Ranson criteria, APACHE III, and MOF scores recorded every 2 to 3 days
      decreased in the TEN group, whereas those in the TPN group increased. Only the
      difference in the third Ranson criteria (mean 6.3 days after admission) for the
      TEN and TPN groups (0.5 vs 2.8, respectively) reached statistical significance (p
      = .002). Stress-induced hyperglycemia was worse in the TPN group, as serum
      glucose levels increased significantly over the first 5 days of hospitalization
      (p < .02), whereas those in the TEN group showed no significant change. An
      exacerbation of pancreatitis, occurring in one TEN patient when the nasojejunal
      tube was dislodged into the stomach, resolved after placement back in the
      jejunum. Three patients who became asymptomatic and normalized amylase on TEN
      flared upon advancing to diet by mouth. CONCLUSIONS: TEN for acute pancreatitis
      is as safe and effective, but is significantly less costly than TPN. Compared
      with TPN, TEN may promote more rapid resolution of the toxicity and stress
      response to pancreatitis. TEN via jejunal feeding should be used preferentially
      in this disease setting.

PMID- 9002081
TI  - Plasma amino acid concentrations in term-born infants fed a whey predominant or a
      whey hydrolysate formula.
AB  - BACKGROUND: Hydrolysates are used in the treatment and prevention of cows milk
      protein allergy. Hydrolysis might alter the plasma level of amino acids. METHODS:
      Forty-five infants were included in a double-blind prospective study and were
      randomized in two groups: one receiving a whey predominant formula (n = 20) and
      the second group receiving a whey hydrolysate formula (n = 25). Weight and length
      gain was evaluated up to the age of 13 weeks, when blood was sampled for
      determination of fasting plasma amino acids. RESULTS: Four infants of the
      hydrolysate group dropped out because refusal to ingest the formula. Weight and
      length gain at 13 weeks of age were extremely comparable. Significant differences
      in plasma concentrations were observed for a number of nonessential and essential
      amino acids (p = .035 to .0001). Threonine and lysine were both higher in the
      hydrolysate group, and aspartic acid, cystine, methionine, tyrosine,
      phenylalanine, histidine, and arginine were lower in the hydrolysate group.
      CONCLUSIONS: These differences in plasma amino acid levels have to be regarded
      with care because all concentrations were within normal ranges, with the
      exception of threonine. Weight and length gain of the hydrolysate and the whey
      predominant formula were identical.

PMID- 9002082
TI  - Total parenteral nutrition increases uptake of latex beads by Peyer's patches.
AB  - BACKGROUND: Dysfunction of the intestinal barrier, as evidenced by increased
      intestinal permeability and bacterial translocation, has been reported under
      total parenteral nutrition (TPN). However, the role of Peyer's patches on the
      intestinal barrier in TPN is not well understood. We investigated whether TPN
      alters the uptake of microparticles by the follicle-associated epithelium of
      Peyer's patches. METHODS: Twenty rats were divided into two groups, a control
      group and a TPN group. Fluorescent polystyrene latex beads, 3.2 +/- 0.2 microns
      in diameter, were used as a probe for measuring the uptake by Peyer's patches.
      After 1 week of consuming either the control or TPN diet, rats were killed. On
      the day of killing, 0.1 mL of latex beads solution was injected into a 1-cm
      length of ileal loop, within 10 cm of the ileocecal valve. Samples were taken
      after 30 minutes of injection, sectioned by cryostat, and then viewed under a
      fluorescent microscope. Follicle-associated epithelial length and particles were
      counted using a confocal laser scanning microscope. The number of particles
      within each compartment was standardized per unit length of epithelium of Peyer's
      patches. RESULTS: Particle numbers within Peyer's patch dome of the TPN group
      were significantly increased compared with those of the control group (p < .01).
      CONCLUSIONS: These data suggest that dysfunction of the intestinal barrier in TPN
      might be associated with a change of uptake by Peyer's patches.

PMID- 9002083
TI  - Adverse metabolic and microbiological effects of tube feeding in experimental
      canine obstructive jaundice.
AB  - BACKGROUND: Inadequate oral intake and poor absorption result in malnutrition in
      obstructive jaundice. Both malnutrition and obstructive jaundice promote
      bacterial translocation from the gut. This study was designed to test the
      efficacy of tube feeding in preventing malnutrition and in decreasing the
      metabolic and microbiological adverse effects in obstructive jaundice. METHODS:
      Forty adult mongrel dogs were studied and were allocated into one of four groups:
      group I (PO-control) underwent sham ligation of the common bile duct (CBDL) and
      was fed ad libitum on Portagen (Mead Johnson, Evansville, IN); group II (PO-CBDL)
      underwent CBDL and was ad libitum fed on the same formula; group III (FEG
      control) underwent sham CBDL and received forced esophagogastric feeding (FEG)
      with Portagen; and group IV (FEG-CBDL) underwent CBDL and received FEG. All the
      animals underwent insertion of a F-12 feeding tube to the stomach from an
      esophagotomy wound on day 1 and the tube was used for continuous enteral feeding
      with Portagen over 4 h/d from day 2 until day 13 in groups III and IV. Fourteen
      days later, blood samplings were done and a laparotomy was performed to obtain
      liver, mesenteric lymph nodes (MLN), and terminal ileum for quantitative
      bacterial culture. Bacterial translocation to MLN and liver was represented by
      log10 CFU/g of tissue in this study. RESULTS: Both group II and IV animals with
      CBDL significantly lost body weight (p = .0001) and had a lower level of
      prealbumin (p = .0054). A significant increase in bacterial translocation to MLN
      and to liver occurred in groups II and IV (p = .0017 and .0268, respectively).
      Intestinal bacterial population was also higher in these two groups than in the
      other two controls (p = 0.0028). An increase in plasma ammonia level was found in
      dogs with CBDL (p = .0002) and in dogs with FEG (p = .003), compared with their
      respective controls. Three among 13 dogs in group IV died and no mortality
      occurred in the other groups (p = .223). CONCLUSIONS: Tube feeding fails to
      improve malnutrition in obstructive jaundice and is associated with intestinal
      bacterial overgrowth, promoting bacterial translocation to MLN and liver,
      precipitating liver dysfunction and consequently a higher mortality.

PMID- 9002084
TI  - Neurologic disorders due to brain manganese deposition in a jaundiced patient
      receiving long-term parenteral nutrition.
AB  - BACKGROUND: Neurologic and radiologic disorders have been reported in patients
      receiving long-term parenteral nutrition (PN). On the basis of elevated serum
      manganese levels, some of these abnormalities have been attributed to manganese
      intoxication. Alterations of the basal ganglia signal intensity on T1-weighted
      magnetic resonance images (MRIs) have been previously reported, but the precise
      nature of these alterations remains controversial although the deposition of
      manganese has been suggested in patients with chronic hepatic encephalopathy due
      to liver failure. METHODS: We report the case of a patient who was receiving PN
      and exhibited a chronic cholestasis. Neurologic disorders appeared after several
      months of PN, when a hypersignal in the basal ganglia and white matter was found
      on T1-weighted MRIs of the brain in association with elevated serum and manganese
      levels. RESULTS: Elevated autopsic concentrations of manganese were found in the
      radiologic abnormal cerebral areas. CONCLUSIONS: Our observation is the first
      demonstration of a relationship between high intracerebral manganese levels,
      radiologic abnormalities, and neurologic disorders during long-term PN. Moreover,
      serum manganese levels are not a good indicator of cerebral levels. In fact, in
      our patient, serum manganese levels returned to normal, whereas those of cerebral
      manganese remained increased.

PMID- 9002085
TI  - Skeletal muscle weakness and dysphagia caused by acid maltase deficiency:
      nutritional consequences of coincident celiac sprue.
AB  - BACKGROUND: A 30-year-old woman with celiac sprue had progressive weight loss,
      myalgia, limb-girdle weakness, and dysphagia. METHODS AND RESULTS: Barium swallow
      showed an atonic esophagus, and scintigraphic study confirmed esophageal
      dysmotility. Skeletal muscle biopsy showed characteristic appearances of acid
      maltase deficiency, which was confirmed by a reduction of leukocyte acid alpha
      glucosidase activity. CONCLUSIONS: Nutritional factors may have accelerated the
      presentation of the lysosomal storage disorder. This is the first reported case
      of dysphagia caused by esophageal motor weakness in acid maltase deficiency.

PMID- 9002086
TI  - Skin necrosis: an unusual complication of hyperphosphatemia during total
      parenteral nutrition therapy.
AB  - BACKGROUND: Hyperphosphatemia complicated by calcification of subcutaneous
      arteries and skin infarcts are very rarely reported in the absence of chronic
      renal failure (CRF). We describe identical lesions in an obese woman with sepsis.
      Hyperphosphatemia resulted from an unintended excess of phosphate in her total
      parenteral nutrition (TPN) formulations. She did not have CRF or
      hyperparathyroidism. METHODS: The patient's records during 37 weeks of
      hospitalization 12 years ago and, subsequently, her outpatient records were
      reviewed. RESULTS: During a 7-week period, the total elemental phosphorus infused
      daily, as divalent phosphate, ranged from 1.8 to 4.2 g, median 3.1, over triple
      the normal daily requirement. This excess was unintended. This occurred before
      the current practice of pharmacist-monitoring of TPN formulations, and possibly
      resulted from misinterpretation of a revised formulation sheet, newly introduced
      to the nursing units at the start of that period. Serum phosphorus increased to
      3.02 mmol/L (normal 0.76 to 1.46 mmol/L). She developed calcification of
      subcutaneous arteries, which was complicated by widespread infarcts of the
      anatomically related skin and subcutis, apparently the result of hypoperfusion of
      these vessels during an episode of septic shock. The infarcts were heralded by
      unusual, blotchy skin discolorations. CONCLUSIONS: This report, illustrating a
      startling cutaneous complication associated with apparent misinterpretation of
      TPN formulations, demonstrates a pathogenetic relationship between
      hyperphosphatemia, calcification of subcutaneous arteries, and necrosis of the
      skin and subcutis in the absence of CRF and hyperparathyroidism and introduces a
      new differential diagnosis for unusual skin lesions appearing during TPN therapy.

PMID- 9002087
TI  - Keratoconus detection based on videokeratoscopic height data.
AB  - PURPOSE: To develop a videokeratoscopic-based keratoconus detection scheme that
      avoids the ambiguity of dioptric power definitions and videokeratoscope design.
      METHODS: Corneal height data obtained with a commercial videokeratoscope are
      decomposed into the set of orthogonal Zernike polynomials. Expansion coefficients
      of a "normal" group and a keratoconus group are compared to find significant
      differences. Elevated Zernike terms are used to detect the disease in these
      populations. The performance of this detection scheme is compared to other
      videokeratoscopic keratoconus Indices. RESULTS: Two low-order Zernike polynomial
      terms are identified as being elevated in keratoconus patients and combined to
      form a new detection index. This index performed at least as well as keratoconus
      detection schemes based on the inferior-superior (I-S) value, the steepest radial
      axes (SRAX), and the Surface Asymmetry Index (SAI) for the samples studied.
      CONCLUSION: The proposed Zernike scheme offers a potentially viable algorithm for
      detecting keratoconus that avoids the ambiguities of dioptric power definitions
      and is independent of videokeratoscope design.

PMID- 9002088
TI  - Feasibility of fitting contact lenses with apical clearance in keratoconus.
AB  - Despite the wide variety of rigid contact lens fitting philosophies for the
      visual correction of keratoconus, questions remain, including which approach
      flat, divided support, or steep-contributes the most toward the preservation of a
      clear cornea. One goal of the Collaborative Longitudinal Evaluation of
      Keratoconus (CLEK) Pilot Study was to determine the feasibility of managing early
      keratoconus patients with apical clearance rigid contact lenses. Of 30
      keratoconus patients identified with at least 1 nonscarred cornea, 17 patients
      (30 eyes) were randomly assigned to a steep lens fitting protocol. After trial
      fitting with a standardized lens design demonstrating minimum apical clearance,
      lenses were dispensed whose base curve was 0.2 mm steeper than the minimum apical
      clearance lens. Patients were re-evaluated on a quarterly schedule concluding at
      12 months. Changes in keratometry between baseline and 12 months identified
      unequal steepening of the flat and steep corneal curvatures, suggestive of
      corneal molding. Best corrected rigid lens visual acuity measures illustrated no
      significant changes over the course of the study. Clinically significant corneal
      compromise was transiently observed in some patients. Only 1 of 22 eyes
      completing the pilot study and fitted with apical clearance developed mild
      corneal scarring.

PMID- 9002089
TI  - Infrared pupillometry in presbyopes fitted with soft contact lenses.
AB  - The influence of pupil size, lens centration, and translation on multifocal
      contact lens performance suggests that these parameters should be accounted for
      in the optical design of presbyopic contact lenses. The purpose of the present
      article is to complete the existing experimental data with clinical measurements
      of pupil diameter and lens position relative to the pupil in a group of
      presbyopes, with controlled target luminance, stimulus distance, gaze angle, and
      convergence. The experiments involve an infrared video-pupillometer and ring
      marked contact lenses. Results on pupil aperture show that the effect of changing
      target distance is comparable in magnitude to that of varying luminance within
      the photopic range. The measured data on lens position confirm that soft contact
      lenses are generally decentered from the pupillary axis, usually in inferior
      temporal direction, and that their average translation between primary and
      downward gaze is very small. It is also found that the average relative position
      between lens and pupil centers is slightly modified by changes of luminance in
      far vision. All these results provide characteristic values which are helpful for
      the optical modelling of presbyopic contact lenses.

PMID- 9002090
TI  - Pilocarpine gel for the treatment of demodicosis--a case series.
AB  - BACKGROUND: Excessive numbers of the mite, Demodax folliculorum, in the eyelash
      follicies cause itching and is referred to as demodicosis. We evaluated 4%
      pilocarpine gel as a treatment for this condition. METHODS: An advertisement was
      placed in a retirement home newsletter, requesting persons with ocular
      discomfort. Respondents were examined for Demodex and persons with abundant mites
      were invited to participate. One eye was treated with pilocarpine gel; the other
      eye was untreated. The relative abundance of mites was evaluated at baseline,
      after 1 and 2 weeks of treatment. Subjects kept a daily log of symptoms. RESULTS:
      Eleven of 22 persons with ocular itching had abundant Demodax. Mites were reduced
      significantly by the treatment (p = 0.017). The amount of mite reduction was
      closely correlated with the extent to which itching was alleviated (r = 0.811, p
      = 0.008). CONCLUSION: Abundant Demodex is an important cause of ocular itching in
      older persons. Mites can be reduced with pilocarpine gel and itching alleviated.

PMID- 9002091
TI  - The pH of multi-purpose soft contact lens solutions.
AB  - Contact lens patient discomfort has been linked to the pH of lens care solutions
      differing from that of tears. To determine if this is a potential problem with
      multi-purpose soft contact lens solutions, we used a Fisher Scientific Accumet
      950 pH/ion meter (accuracy +/- 0.05 pH units) to measure the pH of 3 multi
      purpose solutions-Alcon's Opti-One, Allergan's Complete, and Bausch & Lomb's
      ReNu. The resulting pH values were compared to the threshold for ocular
      awareness, which is outside the zone of 6.6 to 7.8, and the pH value of tears of
      7.45. Each solution was dispensed and measured daily over a 23- to 36-day period
      using 15-ml increments to simulate the amount used on a daily basis. The average
      pH of solutions tested were 7.18 +/- 0.02 for ReNu, 6.97 +/- 0.02 for Opti-One,
      and 7.55 +/- 0.02 for Complete. The highest and lowest pH values of all three
      multi-purpose solutions were found to be within the zone of ocular comfort and
      remained within a narrow value range throughout the testing period. Therefore, pH
      induced discomfort is unlikely to occur when using these solutions on a daily
      basis. Nonetheless, practitioners should select lens care products carefully to
      ensure that the prescribed regimen meets the patient's needs.

PMID- 9002092
TI  - Fitting characteristics of 1-day and 14-day Acuvue disposable contact lenses.
AB  - The fitting characteristics of 1-day Acuvue disposable soft contact lenses (SCLs)
      [base curve (BC) 9.0 mm, diameter 14.2 mm] and 14-day Acuvue disposable SCLa (BC
      8.8 mm, diameter 14.0 mm) were evaluated and compared with respect to lens
      centration and post-blink movement in primary gaze and in upgaze. In this double
      blind study 25 successful daily wearers of either the 1-day lens or the 14-day
      lens with the same parameters were randomly fit with three 1-day lenses and three
      14-day lenses for a total of 6 lenses per eye. The lene fit was evaluated 5 min
      after insertion. Lens centration was assessed by measuring temporal, nasal,
      superior and inferior limbal coverage, and then comparing the net horizontal
      centration (temporal minus nasal coverage) and the net vertical centration
      (superior minus inferior coverage) of the 1-day and 14-day lenses. There was no
      significant difference between the two lenses in terms of temporal, superior, and
      inferior limbal coverage (p > 0.05). However, the 1-day lens showed statistically
      more nasal coverage (p < 0.05). No statistically significant difference in
      movement or in horizontal and vertical differences in centration were found (p >
      0.05). Although our findings indicate a subtle statistical difference in fitting
      characteristics, clinically the two lenses should provide similar fits.

PMID- 9002093
TI  - The expanding spectrum of Bartonella infections: I. Bartonellosis and trench
      fever.

PMID- 9002094
TI  - Urinary tract infections in young febrile children.
AB  - UTI is a common and important clinical problem in infants and young children,
      with a prevalence of 5.3% among febrile infants seen in our Emergency Department.
      White females with rectal temperature > or = 39 degrees C are at particularly
      high risk (prevalence, 17%). Several studies have highlighted the limitations of
      the standard urinalysis for identifying UTI in infants and young children and
      have recommended performance of both urinalysis and urine culture. Alternative
      methods such as dipstick urinalysis, although attractive because of ease of
      performance, are inadequate as a screen for UTI. Hemocytometer WBC counts of an
      uncentrifuged urine specimen can be performed in an office or hospital-based
      laboratory with minimal training. Performance of Gram-stained smears, however, is
      most appropriate for the hospital-based laboratory. In the hospital setting where
      both tests can readily be performed, the positive predictive value of the
      combination of pyuria and bacteriuria (85%) allows prompt institution of
      antimicrobial therapy before culture results are available, whereas the lower
      positive predictive value of the single finding of either pyuria or bacteriuria
      (40%) justifies delaying treatment decisions until culture results are available.
      In the office setting where hemocytometer counts can easily be performed,
      culturing only specimens with pyuria and those of children presumptively treated
      with antimicrobials will result in the identification of almost all patients with
      true UTI, sparing large health care expenditures. Although the urine culture is
      traditionally regarded as the gold standard of UTI, positive urine cultures may
      occur secondary to contamination or in cases of ABU, leading to a false diagnosis
      of UTI. In contrast we found pyuria to be a reliable marker to discriminate
      infection from colonization of the urinary tract. The sustained absence of an
      inflammatory response, on repeat UA within 24 h, constitutes strong evidence that
      infection is absent. Management of ABU is controversial; many experts recommend
      withholding antibiotics because eradication of low virulence organisms may be
      followed by colonization with more virulent species that cause pyelonephritis.
      Preliminary results of our ongoing treatment trial suggest that management of
      young febrile children with UTI as outpatients receiving oral cefixime is as
      efficacious as inpatient management with intravenous cefotaxime. Results of renal
      ultrasound and DMSA scan at the time of infection have not modified management in
      any patient. Accordingly selective rather than routine performance of ultrasound
      is recommended. A voiding cystourethrogram at 1 month and a DMSA scan 6 months
      later have been valuable in identifying patients with vesicoureteral reflux and
      renal scarring, respectively. Among patients initially identified as having acute
      pyelonephritis, the incidence of renal scarring at 6 months has been
      substantially more frequent (approximately 40%) than we had expected. However,
      the long term implications of small scars identified with renal scintigraphy
      remain to be determined.

PMID- 9002095
TI  - Neonatal airway colonization with gram-negative bacilli: association with
      severity of bronchopulmonary dysplasia.
AB  - BACKGROUND: Airway colonization with Gram-negative bacilli (GNB) and Gram
      positive cocci (GPC) is common in mechanically ventilated neonates. Whether GNB
      are related to nosocomial bloodstream infection (BSI) and/or to the severity of
      bronchopulmonary dysplasia (BPD) is unknown. METHODS: We prospectively examine
      this relationship using a cohort design. Data from 260 < or = 1250-g birth weight
      inborn infants (1991 to 1995) intubated > or = 2 weeks included 917 serial
      tracheal cultures and 583 blood cultures. The severity of BPD was assessed by
      duration of mechanical ventilation, oxygen dependency at 36 weeks of
      postconceptional age and the use of home oxygen supplementation. RESULTS: After 2
      weeks of ventilation, 80% of the infants were colonized with GPC (Staphylococus
      epidermidis and Staphylococcus haemolyticus in 90% of the cases). Superimposed on
      36% of these infants was GNB airway colonization with Klebsiella pneumoniae
      (25%), Enterobacter cloacae (25%), Escherichia coli (25%), Pseudomonas aeruginosa
      (10%), Serratia marcescen (10%), Acinetobacter baumannii and Haemophilus
      influenzae (5%). Comparison between 174 GPC- and 86 GNB-colonized infants showed
      that demographics, birth weight, gestational age, perinatal risk factors and
      mortality were similar. Fifteen percent of GNB-colonized infants developed BSI
      caused by GNB and 14% developed BSI caused by GPC. No significant temporal
      relationship between airway colonization and BSI was noted. GNB infants were
      ventilated longer and required oxygen at 36 weeks of postconceptional age and
      home oxygen supplementation twice as often as infants colonized only with GPC.
      GNB colonization was a predictor of severe BPD after controlling for ventilation.
      Ureaplasma colonization occurred in 28% of GNB-colonized and 33% of noncolonized
      infants and was not a predictor of BPD severity. CONCLUSION: GNB airway
      colonization creates a moderate risk for BSI. Antibiotic treatment does not
      regularly eradicate GNB. GNB airway colonization is associated with severe BPD,
      but further studies will be necessary before therapeutic efforts to eradicate GNB
      from the airways should be undertaken.

PMID- 9002096
TI  - Monocyte phagolysosomal fusion in children born to human immunodeficiency virus
      infected mothers.
AB  - BACKGROUND: Previously we demonstrated that monocyte phagolysosomal fusion is
      impaired in chronic HIV infection in adult patients. METHODS: We studied the
      phagolysosomal fusion of peripheral blood monocytes from 45 children vertically
      infected with HIV, 38 noninfected infants born to HIV-positive mothers and 14
      children born to HIV-seronegative women, by a cytomorphologic method in which
      acridine orange is used as a fusion marker. RESULTS: The mean percentages of
      phagolysosomal fusion +/-SD were 42 +/- 16.1 for HIV-positive children, 55.3 +/-
      15.5 for HIV-negative infants born to HIV-infected mothers and 58.2 +/- 12.7 for
      normal controls. Monocyte phagolysosomal fusion of HIV-infected children was
      significantly decreased in comparison to noninfected and normal infants (P <
      0.001), while there was no difference between the two latter groups.
      Phagolysosomal fusion impairment in HIV-infected infants inversely correlated
      with age (r = -0.4527; P < 0.002) and directly correlated with CD4+ T cell counts
      (r = 0.393; P = 0.03). Moreover, phagolysosomal fusion strongly correlated with
      clinical manifestations; this function was significantly impaired in moderately
      and severely symptomatic HIV-infected children with respect to those who remained
      asymptomatic or mildly symptomatic (P < 0.05). CONCLUSIONS: Our results suggest
      that monocyte function in HIV-infected children progressively deteriorates,
      closely related to the severity of the clinical symptoms.

PMID- 9002097
TI  - Computer-generated recall letters for underimmunized children: how cost
      effective?
AB  - OBJECTIVE: To evaluate the effectiveness and cost effectiveness of computer
      generated recall letters to parents of children overdue for immunizations.
      METHODS: This randomized controlled trial included children of two facilities in
      a regional health maintenance organization. Parents of 20-month-olds who had not
      yet received a measles-mumps-rubella (MMR) immunization were identified via a
      computerized immunization tracking system. One half were mailed personalized
      letters that included the recommended immunization schedule and a request to call
      for an appointment; the other half served as a control group. Receipt of the MMR
      between 20 and 24 months of age was evaluated with the computerized tracking
      system. A telephone survey was conducted with parents whose children had not
      received the MMR by 24 months. Decision analysis was used to project the
      theoretical outcomes and costs of a recall letter policy for other populations.
      RESULTS: Among 20-month-old children 10% had not received the MMR; 289 families
      were included in the analysis. Of families who were mailed letters, 54% (82 of
      153) received the MMR by 24 months of age, compared with 35% (47 of 136) of those
      in the control group (P = 0.001). The telephone survey was completed with 110
      parents of children who still did not appear on the health plan computer as
      having received the MMR by 24 months. Fifteen percent said the child had received
      an immunization at an outside provider, and of the rest 62% said they had not
      been aware that an immunization was due. In the cost effectiveness analysis it
      was projected that recall letters would increase the immunization rate for the
      regional population of approximately 30000 children from 86% to 90% at a total
      cost of $5031 annually. The cost per additional child appropriately immunized was
      $4.04. In sensitivity analyses this cost effectiveness ratio varied depending on
      the baseline population coverage rate as well as the estimated effectiveness of
      recall letters. CONCLUSIONS: Computer-generated letters to recall children
      overdue for immunizations resulted in a higher proportion of children
      appropriately immunized in this setting. However, the strategy was not as cost
      effective as intuition might suggest. Further studies in health maintenance
      organization (HMO) settings should compare the cost effectiveness of letters with
      other low cost strategies including automated telephone reminders.

PMID- 9002098
TI  - Parainfluenza virus type 4 infections in pediatric patients.
AB  - BACKGROUND: The purpose of this study was to describe the clinical
      characteristics and epidemiology of parainfluenza virus type 4 infections in
      pediatric patients. METHODS: Hospital records of 13 patients from whom
      parainfluenza virus type 4 was isolated were retrospectively reviewed. RESULTS:
      Parainfluenza virus type 4 infection was associated with upper respiratory tract
      disease, severe lower respiratory tract disease requiring hospitalization in 10
      of 13 patients and aseptic meningitis. Nine of the 10 hospitalized patients were
      < 24 months old (mean age, 8.3 months) and required hospitalization for 4 to 25
      days (mean, 5.5 days). CONCLUSIONS: Serious illnesses associated with
      parainfluenza virus type 4 infections are more common than previously recognized.

PMID- 9002099
TI  - Penetration of clarithromycin into middle ear fluid of children with acute otitis
      media.
AB  - OBJECTIVE: To determine the steady state plasma and middle ear fluid
      concentrations of clarithromycin and its metabolite, 14(R)-hydroxyclarithromycin
      in 32 pediatric patients with acute otitis media. METHODS: After the sixth dose
      of a 7.5-mg/kg every-12-h regimen of clarithromycin suspension, tympanocentesis
      was performed at 2, 4, 8 or 12 hours postdose. Plasma and middle ear fluid
      samples were assayed for concentrations of clarithromycin and its 14-hydroxy
      metabolite. RESULTS: Mean middle ear fluid concentrations ranged from 3.0 to 8.3
      micrograms/g during the dosing interval for clarithromycin and from 1.5 to 3.8
      micrograms/g for 14(R)-hydroxyclarithromycin. The mean middle ear fluid
      concentrations were consistently greater than corresponding mean plasma
      concentrations, which ranged from 0.7 to 3.4 micrograms/ml for clarithromycin and
      from 0.8 to 1.8 micrograms/ml for 14(R)-hydroxyclarithromycin. The ratios of
      middle ear fluid to plasma concentration appeared to increase during the dosing
      interval and were 8.8 and 3.8 for clarithromycin and 14(R)-hydroxyclarithromycin,
      respectively, 12 h after dosing. CONCLUSIONS: Multiple oral doses of
      clarithromycin suspension produced sustained middle ear fluid concentrations of
      clarithromycin and 14(R)-hydroxyclarithromycin which exceed the minimum
      inhibitory concentrations of most otic pathogens.

PMID- 9002100
TI  - Rhinovirus infection associated with serious lower respiratory illness in
      patients with bronchopulmonary dysplasia.
AB  - OBJECTIVE: To determine the characteristics of rhinovirus infection in patients
      with bronchopulmonary dysplasia. SUBJECTS AND METHODS: Between July 1, 1993, and
      July 1, 1995, 40 patients with bronchopulmonary dysplasia were identified. Viral
      cultures were obtained in ambulatory patients presenting with an acute
      respiratory illness requiring hospitalization or in hospitalized patients with a
      respiratory deterioration. When rhinovirus was isolated epidemiologic data were
      collected, and the characteristics of the illness, its severity and outcome were
      noted. Key features of rhinovirus and respiratory syncytial virus (RSV)
      bronchiolitis were compared. RESULTS: There were 8 cases of lower respiratory
      tract illness associated with rhinovirus infection in 6 infants (mean age, 7.1 +/
      4.1 months) and 1 child (age, 40 months), an incidence of 0.15 infection/patient
      year. The mean gestational age and birth weight of these patients were 27.3 (+/-
      2.75) weeks and 853 (+/-341) g, respectively. There were 5 males. Four patients
      needed intensive care unit admission and 1 required mechanical ventilation. By
      comparison there were 13 cases of RSV bronchiolitis, an incidence of 0.25
      infection/patient year. The 2 groups were similar epidemiologically and an equal
      proportion of patients with rhinovirus and RSV needed intensive care unit
      admission. A greater percentage of patients with RSV required mechanical
      ventilation (50% vs. 14%), but this difference was not statistically significant.
      Three cases of rhinovirus were nosocomial, and 1 infant had a second infection.
      Four patients required 5 hospitalizations caused by rhinovirus infection, and the
      mean duration of hospital stay was 11 days. All children had sustained worsening
      in their respiratory status after rhinoviral illness requiring additional
      therapy. CONCLUSIONS: Rhinovirus is a common and potentially serious lower
      respiratory pathogen in bronchopulmonary dysplasia patients. Rhinovirus infection
      has lasting pulmonary sequelae in these children.

PMID- 9002101
TI  - Factors associated with unnecessary immunization given to children.
AB  - OBJECTIVE: To determine the factors associated with unnecessary immunization
      during the pre-school years. METHODS: Children were selected from birth
      certificates and their parents were interviewed to identify all immunizations to
      72 months of age. The immunizations were verified. RESULTS: Of 187 children
      studied 34 (18%) received unnecessary immunization. Unnecessary immunization was
      strongly associated with ever receiving immunization in a large system of public
      clinics (designated "Public A") (33%) compared with other providers (5%) (P <
      0.00001). Among children immunized in Public A, unnecessary immunization was
      associated with the parent having an incomplete or no copy of the child's
      immunization record (P = 0.007) and with not being up to date for immunizations
      at 24 months of age (P = 0.04). Complete documentation of immunizations either in
      the Public. A record or in the parent's copy of the record was associated with a
      4% rate of unnecessary immunization; incomplete or no documentation in both the
      Public A and the parent's record was associated with a 45% rate of unnecessary
      immunization (P = 0.001). CONCLUSIONS: Access to a complete immunization record,
      be it the provider's, the parent's or ideally both, decreases substantially a
      child's risk of unnecessary immunization.

PMID- 9002102
TI  - Safety and immunogenicity of Chiron/Biocine recombinant acellular pertussis
      diphtheria-tetanus vaccine in infants and toddlers.
AB  - OBJECTIVE: To evaluate the safety and immunogenicity of the recombinant acellular
      pertussis-diphtheria-tetanus (aPDT) vaccine (C-aPDT, Chiron/Biocine). STUDY
      DESIGN: This is a randomized blinded trial evaluating the safety and
      immunogenicity of the recombinant aPDT vaccine (C-aPDT, Chiron/Biocine) in 2000
      infant recipients compared with 498 controls who received whole cell diphtheria
      pertussis-tetanus (wDPT; Connaught) vaccine at 2, 4 and 6 months of age. In
      addition the safety and immunogenicity of the same C-aPDT vaccine were evaluated
      as a booster dose in a subset of the same population when given at 15 to 18
      months of age and compared with licensed Lederle aPDT vaccine. RESULTS: The C
      aPDT vaccine was associated with very few local or systemic reactions when
      compared with wDPT. In toddlers the local and systemic side effects observed were
      similar after either acellular vaccine. When the immunogenicity of the C-aPDT
      vaccine was compared with the wDPT (Connaught) in infancy, the vaccines were
      equivalent for anti-diphtheria response, the wDPT developed higher anti-tetanus
      response and the C-aPDT vaccine was significantly more immunogenic for all other
      antigens tested. In toddlers the C-aPDT acellular vaccine exhibited equal or
      improved immunogenicity for antigens tested as compared with Lederle aPDT except
      for a higher anti-filamentous hemagglutinin response with the Lederle aPDT
      vaccine. CONCLUSION: The Chiron/Biocine aPDT vaccine offers an improved safety
      profile as well as improved immunogenicity when compared with a licensed wDPT
      product.

PMID- 9002103
TI  - Identification of febrile neonates unlikely to have bacterial infections.
AB  - OBJECTIVE: A prospective study was undertaken to evaluate the usefulness of low
      risk criteria for identifying febrile neonates unlikely to have bacterial
      infections, particularly bacteremia and meningitis. Using these criteria we
      wished to check whether these low risk neonates can be safely managed as
      inpatients under close observation but without receiving empiric antibiotic
      therapy. STUDY DESIGN: We conducted a prospective study of 250 consecutive
      infants 28 days of age or less (range, 4 to 28 days) who had rectal temperatures
      of at least 38 degrees C. After a complete history, physical examination and
      sepsis workup, the 131 febrile neonates with clinical and laboratory findings
      indicating low risk for bacterial infections were hospitalized, closely observed
      and not given antibiotics. The low risk criteria used to identify these neonates
      included well appearance; absence of physical signs of an ear, eye or soft tissue
      infection; a white blood cell count of 5000 to 15,000/mm3, a neutrophil band form
      count of < 1500/mm3, a spun urine specimen that had < 10 white blood cells per
      high power field on microscopy and a C-reactive protein value of < 20 mg/l. The
      remaining 119 febrile neonates who did not meet the low risk criteria were
      hospitalized and given empiric antibiotics pending culture results. RESULTS: The
      overall incidence of bacterial infections in the 250 febrile neonates was 16.4%
      (41 neonates) with bacteremia and/or meningitis occurring in 4.4% (11 neonates).
      Of the 131 low risk neonates only one (0.8%) had a bacterial infection (urinary
      tract infection) compared with 40 (33.6%) among the 119 who did not meet the
      criteria (P < 0.05). The negative predictive value of these criteria for
      excluding bacterial infections was 99.2% (95% confidence interval, 97.7% to
      100%). For bacteremia and meningitis this figure became 100%. However, the
      positive predictive value and specificity of the criteria were too low to
      identify all febrile neonates with bacterial infections. Among the low risk group
      58 (44.3%) were reclassified on the second or third hospital day, because of
      continued fever (35), poor activity (14) and white blood cell count > 15000/mm3
      on a repeat blood test (9). They were given antibiotics, but only 1 had a urinary
      tract infection. This patient was then treated with a 7-day course of
      antibiotics. All low risk neonates recovered uneventfully with no relapses
      observed during their hospital stay or at the time of minimum 1-week outpatient
      follow-up visits. CONCLUSION: By the low risk criteria a substantial number of
      febrile neonates at low risk for bacterial infections can be identified and
      managed safely as inpatients without antibiotic therapy.

PMID- 9002104
TI  - Suppurative thrombophlebitis in children: a ten-year experience.
AB  - OBJECTIVE: To determine the clinical and diagnostic features, complications,
      management and prevention of superficial suppurative thrombophlebitis (ST) in
      children < 18 years of age. STUDY DESIGN: A retrospective review of medical
      records was performed for patients in two urban hospitals from January 1, 1985,
      through June 30, 1995, with a discharge diagnosis of phlebitis. RESULTS: We
      identified 21 patients, including 12 neonates, with ST. The majority had
      underlying medical conditions or preceding invasive procedures and administration
      of broad spectrum antibiotics or total parenteral nutrition as possible
      predisposing factors. More than two-thirds had localizing signs (swelling,
      erythema, induration or a palpable cord); one-third had purulent drainage from
      the vein. Septicemia was present in one-third of patients. Fever and tenderness
      were present in older children. Nearly one-half had involvement of an upper
      extremity. Cultures of vein (63%), blood (67%) or abscess (86%) grew pathogens in
      most. Gram-positive organisms were predominant; Staphylococcus aureus was
      isolated from 44%, Gram-negative enterics from 16.7% and Candida species from
      another 16.7% of patients. Eleven children had vein excision, whereas 10 had only
      incision and drainage. Complications, including death in one patient, occurred in
      33% but could not be correlated with age or method of surgical intervention.
      CONCLUSIONS: ST is a rare but serious nosocomial infection in infants and
      children that results in substantial morbidity. It should be suspected in any
      hospitalized child who is or was receiving intravenous fluids and who has fever,
      localizing signs or persistent bacteremia. Prompt vein excision, with adjunctive
      antimicrobial therapy, is the recommended treatment.

PMID- 9002105
TI  - Recovery from rhinocerebral mucormycosis with carotid artery occlusion: a
      pediatric case and review of the literature.

PMID- 9002106
TI  - Evaluation of a pentavalent conjugated pneumococcal vaccine in toddlers.

PMID- 9002107
TI  - The course of chickenpox in asthmatic children receiving inhaled budesonide.

PMID- 9002108
TI  - Congenital toxoplasmosis acquired from an immune woman.

PMID- 9002109
TI  - Osteitis of the calcaneus caused by Mycobacterium xenopi.

PMID- 9002110
TI  - Penetration of cefpodoxime into middle ear fluid in pediatric patients with acute
      otitis media.

PMID- 9002111
TI  - Congenital brucellosis in a premature infant.

PMID- 9002113
TI  - Low risk of congenital toxoplasmosis in children born to women infected with
      human immunodeficiency virus.

PMID- 9002114
TI  - Vitamin A therapy for respiratory syncytial virus infection.

PMID- 9002115
TI  - Usefulness of the chest radiograph in the diagnosis of lower respiratory
      infection.

PMID- 9002116
TI  - Historical perspective--use of ciprofloxacin in children.

PMID- 9002112
TI  - Outbreak of echovirus type 33 infection in Japanese school children.

PMID- 9002117
TI  - Pathogenesis of bacterial bronchitis in cystic fibrosis.
AB  - OBJECTIVE: To describe the current understanding of the pathogenesis of
      infections in cystic fibrosis (CF). SUMMARY: The key element in the pathogenesis
      of infections in CF is the abnormal mucin resulting from a defective chloride
      channel. Abnormal mucin and the lack of hydration of respiratory secretions
      entraps bacteria, permitting colonization and subsequent infection. "Normal"
      physiologic insults, such as microaspiration, and pollution evoke mucin secretion
      with bacteria-mucin aggregates causing infection of small airways. Microcolonies
      of pulmotropic bacteria (i.e. Haemophilus and Staphylococcus) in the trapped
      mucin cause mucosal injury which predisposes the patient to Pseudomonas
      aeruginosa infection. Eventually there is obstruction of medium-sized and small
      airways by inflammatory exudate and mucus. Ultimately these chronic endobronchial
      bacterial infections cause significant loss of pulmonary function with morbidity
      and a decrease in the life span of patients with CF. Although antibiotic therapy
      is beneficial for the management of bacterial respiratory tract infections in CF
      patients, gene therapy may provide the ultimate cure. CONCLUSION: New treatment
      strategies will emerge as the pathogenesis of cystic fibrosis is better
      elucidated.

PMID- 9002118
TI  - Sequential ciprofloxacin therapy in pediatric cystic fibrosis: comparative study
      vs. ceftazidime/tobramycin in the treatment of acute pulmonary exacerbations. The
      Cystic Fibrosis Study Group.
AB  - BACKGROUND: Cystic fibrosis patients have chronic bacterial infections of the
      respiratory tract, most commonly Pseudomonas aeruginosa. Although controversial,
      administration of antibiotic therapy during acute pulmonary exacerbations is
      standard practice. Fluoroquinolones are currently not indicated for use in young
      children because of the observation of arthropathy and damage to growing
      cartilage in beagle puppies. Because of its activity against P. aeruginosa and
      excellent oral bioavailability, ciprofloxacin offers a unique therapeutic
      alternative for this patient population. OBJECTIVE: This prospective, randomized,
      double blind study compared the efficacy and safety of sequential
      intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized
      pediatric cystic fibrosis patients with an acute pulmonary exacerbation
      associated with P. aeruginosa infection. METHODS: One hundred thirty patients
      (ages 5 to 17 years) were randomized to receive either i.v. ciprofloxacin 10
      mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for
      a minimum of 3 days or i.v. ceftazidime 50 mg/kg every 8 h plus i.v. tobramycin 3
      mg/kg every 8 h for a minimum of 10 days. Clinical, bacteriologic and safety
      responses were assessed throughout the study. RESULTS: All 84 patients (median
      age, 11 years; range, 5 to 17 years) valid for efficacy in both treatment groups
      demonstrated clinical improvement. Five patients experienced clinical relapses (3
      ciprofloxacin, 2 ceftazidime/tobramycin) by the 2- to 4-week follow-up. Intent-to
      treat analysis demonstrated similar clinical findings between the two treatment
      groups at both the end of therapy and follow-up. Clinical improvement correlated
      with improvement in pulmonary function studies and the acute clinical scoring
      system but not with bacteriologic eradication of Pseudomonas. DNA profiles
      demonstrated that irrespective of colony morphology, usually one clonal strain
      was associated with each patient's pulmonary exacerbation. Treatment-associated
      musculoskeletal events occurred with equal frequency (22% vs. 21%) in both study
      drug groups (n = 129), and arthralgias were within the range of rates for cystic
      fibrosis arthropathy. None of these events required study drug discontinuation.
      CONCLUSION: Sequential i.v./oral ciprofloxacin monotherapy offers a safe and
      efficacious alternative to standard parenteral therapy for acute pulmonary
      exacerbations in pediatric cystic fibrosis patients.

PMID- 9002119
TI  - Ciprofloxacin as antipseudomonal treatment in patients with cystic fibrosis.
AB  - OBJECTIVE: The efficacy and safety of oral ciprofloxacin as a maintenance
      antipseudomonal therapy were evaluated in 44 patients with cystic fibrosis who
      had completed a 14-day regimen of intensive hospital therapy with intravenous
      ceftazidime and amikacin, supplemented by amikacin inhalation therapy. METHODS:
      Twenty-one patients were randomly assigned to oral ciprofloxacin alone (Group I)
      and 23 received ciprofloxacin plus inhaled amikacin (Group II). RESULTS: Negative
      sputum cultures were achieved in 34 patients (77%) at the end of intensive
      therapy (19 Group I and 15 Group II) and were sustained after 3 months of
      maintenance therapy in 5 of the 19 responders in Group I (26%) and in 8 of the 15
      responders in Group II (53%). Resistance to ciprofloxacin was found in 7 of 31
      (23%) sputum isolates at the end of ciprofloxacin therapy. During maintenance
      therapy, continued improvement in clinical symptoms was observed in 14 patients
      in both treatment groups; 6 in each group had further improvements whereas only 4
      patients were clinical failures. There was no correlation between clinical
      outcome and either elimination of Pseudomonas aeruginosa from sputum culture or
      development of ciprofloxacin resistance. Both maintenance regimens were well
      tolerated by this population of patients which included 28 children younger than
      15 years of age. There were no severe or serious adverse events, no signs of
      quinolone-related arthropathy and no growth impairment. CONCLUSION: Ciprofloxacin
      was efficacious, safe and well-tolerated as maintenance antipseudomonal therapy
      in cystic fibrosis patients. These results suggest further evaluation of
      ciprofloxacin as an oral maintenance therapy is warranted.

PMID- 9002120
TI  - Pharmacokinetic disposition of sequential intravenous/oral ciprofloxacin in
      pediatric cystic fibrosis patients with acute pulmonary exacerbation.
AB  - OBJECTIVE: Information about the pharmacokinetics of fluoroquinolone antibiotics
      in high risk children is scant. This study examined the disposition of
      sequentially administered intravenous and oral ciprofloxacin, as well as provided
      dosing recommendations, for the treatment of acute pulmonary exacerbations in
      pediatric cystic fibrosis patients. METHODS: After enrollment in a Food and Drug
      Administration approved protocol, the pharmacokinetic profiles of ciprofloxacin
      (CIP) administered to 18 children with cystic fibrosis (ages 5 to 17 years) were
      studied at steady state after sequentially administered intravenous (10 mg/kg
      every 8 h) and oral (20 mg/kg every 12 h) doses. All children enrolled met
      published criteria for exacerbation of Pseudomonas aeruginosa lung infection and
      received CIP intravenously (given as a 1-h infusion) followed by oral
      administration, each for a minimum of 3 days. All patients were at a mild to
      moderate stage in their disease with National Institutes of Health scores between
      37 and 83. Blood samples were drawn at 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0
      (after both i.v. and oral dosing) and 12 h (oral only) after CIP administration.
      CIP serum concentrations were determined by high performance liquid
      chromatography. RESULTS: After oral CIP mean +/- SD peak serum concentrations and
      peak times were 3.7 +/- 1.4 mg/l and 2.5 +/- 1.8 h, respectively, compared with
      5.0 +/- 1.5 mg/l and 1.0 +/- 0.3 h after completion of the i.v. infusion. Maximum
      concentrations, when normalized for dose, were 0.52 +/- 0.12 and 0.19 +/- 0.07
      mg/l/kg after i.v. and oral dosing, respectively. The mean bioavailability of
      oral CIP for all patients was 76%; younger patients appeared to absorb oral CIP
      less than older subjects, 68% vs. 95%, respectively. For all patients elimination
      half-lives were 2.6 +/- 0.6 and 3.4 +/- 0.7 h after i.v. and oral administration,
      respectively, and did not differ by age. Total clearance after i.v.
      administration was 19.5 +/- 10.9 liters/h. No significant CIP-related adverse
      effects were noted. CONCLUSIONS: CIP doses of 30 mg/kg/day i.v. and 40 mg/kg/day
      orally must be administered to children with cystic fibrosis to achieve optimal
      therapeutic concentrations.

PMID- 9002121
TI  - Rheumatologic aspects of pediatric cystic fibrosis patients treated with
      fluoroquinolones.
AB  - BACKGROUND: The recommended and approved use of fluoroquinolones, including
      ciprofloxacin, is limited to adult patients because of concerns about the
      association of joint toxicity in young animals with quinolone administration and
      rare reports of joint complaints or findings in humans. Despite these warnings
      some quinolones have been used in children for many years, with seemingly minimal
      joint sequelae. OBJECTIVE: This brief review will clarify the association of
      quinolones with arthropathy, particularly ciprofloxacin because of its widespread
      use, and subsequently discuss the problem of defining that association in a
      population of children with cystic fibrosis. RESULTS: Examination of available
      clinical data to date provides no absolute evidence that ciprofloxacin induces
      significant arthropathy in children, in contrast to data reported in some animal
      species. Specifically short term ciprofloxacin-induced joint toxicity appears to
      be low in cystic fibrosis patients who have a significant background prevalence
      of arthralgias and arthritis. However, the level of detection of joint toxicity
      in these small trials may be insufficient to define rare or late adverse effects.
      CONCLUSIONS: Ciprofloxacin-associated arthropathy appears to occur infrequently,
      particularly in children with cystic fibrosis.

PMID- 9002122
TI  - Ciprofloxacin in pediatrics: worldwide clinical experience based on compassionate
      use--safety report.
AB  - BACKGROUND: Quinolone-induced cartilage toxicity has been observed in
      experimental juvenile animal studies and is species- and dose-specific.
      Accordingly these findings have led to the contraindication of fluoroquinolones
      in children. Previous data in 634 adolescents and children treated with
      compassionate use ciprofloxacin demonstrated low rates of reversible arthralgia
      and a safety profile similar to that for adult patients. OBJECTIVE: This report
      describes the safety findings in 1795 children who received 2030 treatment
      courses of intravenous or oral ciprofloxacin. RESULTS: The average doses of
      intravenous and oral ciprofloxacin in the study population were 8 and 25
      mg/kg/day, respectively. Treatment-associated events were reported in 10.9% of
      children receiving oral ciprofloxacin compared with 18.9% among intravenous
      recipients. Overall arthralgia occurred during 31 ciprofloxacin treatment courses
      (1.5%) and the majority of events were of mild to moderate severity and resolved
      without intervention. More than 60% of arthralgia episodes were in children with
      cystic fibrosis. CONCLUSION: The adverse event pattern in children receiving
      ciprofloxacin in this analysis was similar to that observed in adults. Rates of
      reversible arthralgia were low and unchanged from previously published
      surveillance data in children.

PMID- 9002123
TI  - Ciprofloxacin safety in a pediatric population.
AB  - OBJECTIVE: We conducted a retrospective study primarily to estimate the risk of
      musculoskeletal toxicities associated with ciprofloxacin administration in a
      pediatric population. In addition risks of hepatic and renal disorders associated
      with ciprofloxacin therapy were calculated. METHODS: Adverse events in this study
      were restricted to those that required physician referral or hospitalization and
      occurred within 45 days of receiving a prescription for ciprofloxacin. From 2
      resource databases, > 1700 patients < or = 17 years who received at least 1
      ciprofloxacin prescription were identified between January, 1988, and December,
      1993. RESULTS: In this population there were no cases of newly diagnosed acute
      arthritis or serious liver or kidney disease that were likely ciprofloxacin
      induced. One patient was diagnosed with hemolytic-uremic syndrome, which may have
      been exacerbated by ciprofloxacin therapy. CONCLUSIONS: Surveillance of
      ciprofloxacin usage in a pediatric population failed to demonstrate serious or
      unusually high rates of any adverse events, including joint toxicity.

PMID- 9002124
TI  - Use of fluoroquinolones as prophylactic agents in patients with neutropenia.
AB  - BACKGROUND: The use of fluorinated quinolone antibiotics to selectively
      decontaminate the gastrointestinal tract is a reasonable alternative to prevent
      infection in neutropenic patients. The fluoroquinolones represent ideal
      antibiotics with which to achieve the principles of selective decontamination by
      allowing colonization of anaerobes to inhibit the adherence, colonization and
      proliferation of potentially pathogenic aerobic flora. OBJECTIVE: This report
      describes the prophylactic use of fluoroquinolones in neutropenic patients.
      RESULTS: The majority of studies of fluoroquinolone prophylaxis in neutropenic
      patients have shown a reduction in documented Gram-negative bacterial infections.
      However, Gram-positive infections, particularly those with viridans streptococci,
      present a major impediment to the use of single agent prophylaxis with a
      quinolone. CONCLUSION: Prophylaxis with fluoroquinolones in neutropenic patients
      was found to be advantageous, but it must be balanced against the risk of Gram
      positive infections and the potential for antibiotic resistance.

PMID- 9002125
TI  - Use of fluoroquinolones for empirical management of febrile neutropenia in
      pediatric cancer patients.
AB  - BACKGROUND: Empiric antibiotic therapy has become a standard of care for the
      febrile neutropenic patient. Many clinical trials over the previous three decades
      have demonstrated that a variety of antibiotic combinations and more recently
      potent antibiotic monotherapies may preserve the patient through the critical
      time of fever and neutropenia. Recently attempts have been made to identify "low
      risk" patients who may not require traditional, intensive, hospitalized
      intravenous antimicrobial therapy. Therefore the need for new treatment
      alternatives for the febrile neutropenic pediatric cancer patient in particular
      revolves around the desire for less complex regimens, agents with minimal
      toxicity and expense and the option of an oral formulation for outpatient
      management. OBJECTIVE: Fluoroquinolones, especially ciprofloxacin and ofloxacin,
      are examined in this paper as potential oral alternatives for managing the low
      risk neutropenic pediatric cancer patient population. Attention must be paid to
      their antibacterial spectra, however, and in some cases fluoroquinolones should
      be combined with a second agent for additional Gram-positive coverage. RESULTS:
      Several studies, including one ongoing trial at the National Cancer Institute,
      have shown the potential benefits of oral fluoroquinolone therapy among low risk
      febrile neutropenic patients. Joint complaints in children after ciprofloxacin
      therapy in the National Cancer Institute trial thus far have been minimal,
      reversible and felt to be unrelated to ciprofloxacin treatment. CONCLUSION: The
      use of outpatient therapy, such as the fluoroquinolones, to manage febrile
      neutropenic episodes must be approached with caution and should be undertaken
      only in selected low risk patients.

PMID- 9002126
TI  - Risk-benefit experience of ciprofloxacin use in pediatric patients in the United
      Kingdom.
AB  - BACKGROUND: Selection of the most appropriate therapeutic regimen in the
      management of an infectious disease in a small child or infant is often
      difficult. Many antimicrobial agents have side effects, thus stressing the
      importance of risk vs. benefit assessment in the younger patient population.
      Frequent use of an antimicrobial agent provides the practitioner with critical
      data regarding the relative rate and intensity of specific adverse events. In
      addition the benefits of therapy in terms of rapidity of cure, return to normal
      life and economic outcomes may also be appreciated. Oral ciprofloxacin, although
      not currently indicated for use in children, has been available to practitioners
      for > 10 years. OBJECTIVE: Compassionate use experience with ciprofloxacin for
      the treatment of acute, serious infections (i.e. Pseudomonas species) in
      pediatrics is described. RESULTS: To date ciprofloxacin has been a very useful
      agent for the management of serious infections in children and has been
      associated with little risk of permanent joint damage. CONCLUSION: These data
      support the use of ciprofloxacin in children in selected situations where the
      efficacy outweighs any considerable risk, thereby minimizing misuse and overuse
      of this antimicrobial agent.

PMID- 9002127
TI  - Use of ciprofloxacin in developing countries.
AB  - BACKGROUND: The demographic and subsequent economic pressures in developing
      nations have contributed to the increasing levels of antibiotic resistance among
      both commensal flora and pathogenic bacteria. As empirical options are
      diminishing daily, the role of ciprofloxacin in pediatric infections is becoming
      increasingly significant. OBJECTIVE: The levels of resistance among various
      enteric pathogens are described, and the efficacy and safety of ciprofloxacin in
      treating infections such as shigellosis, cholera and Escherichia coli
      gastroenteritis are discussed. The findings of a large study of invasive
      salmonellosis in children in rural Africa are briefly presented, including the
      role of ciprofloxacin in multiresistant invasive disease. In addition the role of
      ciprofloxacin as a chemoprophylactic agent in the control of meningococcal
      disease is discussed. RESULTS: The efficacy and safety of ciprofloxacin in
      children were found to be similar to those observed in adults for
      gastrointestinal infectious diseases. Overall the data presented confirm that
      ciprofloxacin is a safe and efficacious agent for use in children in the
      developing world. CONCLUSION: Ciprofloxacin has been shown to be safe and
      efficacious in children in developing countries. Subsequently a priority for both
      the pharmaceutical industry and regulatory authorities in developing nations is
      to prevent fluoroquinolone misuse and development of antibiotic resistance.

PMID- 9002129
TI  - Thrombin in the management of full thickness macular holes.
AB  - PURPOSE: As thrombin is a known stimulator of retinal glial and pigment
      epithelial cells, we performed a pilot study to evaluate the use of thrombin as
      adjunctive mitogen therapy in vitreous surgery for full-thickness macular holes.
      METHODS: Macular hole surgery was performed on 25 eyes of 24 consecutive patients
      with stage II, III, or IV macular holes. After removal of the posterior hyaloid,
      peeling of epiretinal membranes, and fluid-air exchange, 0.05 mL or 0.1 mL of
      thrombin (100 units/ mL) was placed over the macular hole. After infusion of a
      gas tamponade, the patient's head was kept in a supine position for 1 hour, and
      then was kept in a prone position for approximately 2 weeks. RESULTS: Closure of
      the macular hole with one procedure was achieved in 80% of the eyes. Sixty-five
      percent of the eyes with a closed macular hole achieved a visual acuity of 20/40
      or better. Postoperative inflammation was present in all eyes, and a small
      hypopyon developed in 28% of the eyes. CONCLUSION: Thrombin therapy failed to
      markedly increase the success rate of macular hole surgery.

PMID- 9002128
TI  - Paraproteinemias associated with serous detachments of the retinal pigment
      epithelium and neurosensory retina.
AB  - BACKGROUND: Serous retinal and retinal pigment epithelial detachments resembling
      central serous chorioretinopathy developed in three patients who had
      paraproteinemias. METHODS: The patients in this study were examined at two
      institutions, and their charts, photographs, and fluorescein angiograms were
      reviewed by the authors. Two patients had cryoglobulinemia and one had lgA, lgM
      benign gammopathy. RESULTS: These patients had decreased central visual acuity
      and metamorphopsia at the initial examination. All three patients were women. Two
      patients were taking systemic corticosteroids in tapering doses at the time of
      the initial examination. The multiple serous retinal pigment epithelial and
      retinal detachments were unilateral in one patient and bilateral in two patients.
      Two patients were treated with laser photocoagulation because of chronic visual
      loss and foveal detachments. At the most recent examination, each patient had
      visual acuity of 20/30 or better in both eyes and complete resolution of
      subretinal fluid. CONCLUSIONS: Patients with paraproteinemia may develop multiple
      serous detachments of the retinal pigment epithelium and of the neurosensory
      retina. The chorioretinopathy in these patients may have been related to their
      paraproteinemia, type A personality, corticosteroid use, or a combination of
      these factors. The final visual acuity in these three patients was good.

PMID- 9002130
TI  - Successful treatment of progressive outer retinal necrosis syndrome.
AB  - PURPOSE: Progressive outer retinal necrosis is a destructive retinopathy found in
      patients with acquired immune deficiency syndrome. Treatment of this disorder has
      been unsuccessful in reported patient series, with the patients experiencing
      profound bilateral loss of vision. METHODS: We treated six patients with
      combination antiviral therapy, usually with intravenous foscarnet and either
      ganciclovir or acyclovir. RESULTS: These six patients retained a visual acuity of
      20/100 or better in at least one eye for the remainder of their lives (a period >
      4 months for each patient). Retinal detachments developed in four patients, for
      which vitrectomy and silicone oil tamponade were required. CONCLUSIONS: A
      combination of intravenous antiviral therapy and aggressive vitrectomy techniques
      to repair any associated detachments may allow the preservation of useful visual
      acuity in patients with progressive outer retinal necrosis. This is the first
      reported series of successful long-term treatment of patients with this disorder.

PMID- 9002131
TI  - Rhegmatogenous retinal detachment in eyes with uveal melanoma.
AB  - PURPOSE: To describe the clinical features, surgical management, and outcome of
      patients with uveal melanoma who presented with or later developed a
      rhegmatogenous retinal detachment. METHODS: We retrospectively identified four
      patients who presented with uveal melanoma and rhegmatogenous retinal detachment
      simultaneously and six patients in whom a rhegmatogenous retinal detachment
      developed 11-100 months (mean, 44.8 months) after radiotherapy for a choroidal
      melanoma. RESULTS: All four patients with simultaneous presentation of uveal
      melanoma and retinal detachment underwent successful retinal detachment repair
      (cases 1 and 4, scleral buckle; case 2, pars plana vitrectomy, and case 3,
      pneumatic retinoplexy). Rhegmatogenous retinal detachment occurring after proton
      beam or plaque radiotherapy of uveal melanoma was repaired successfully in five
      of six patients with scleral buckling alone or in combination with pars plana
      vitrectomy. In the short follow-up period of this study, we did not observe tumor
      recurrence either before or after retinal detachment repair. CONCLUSION:
      Rhegmatogenous retinal detachment associated with uveal melanoma may be treated
      successfully using conventional retinal surgical techniques. The benefits of
      retinal detachment repair must be weighed against any theoretical increased risk
      of extra-scleral extension of the melanoma. Long-term follow-up evaluation will
      be required to determine the safety of various retinal detachment repair
      techniques in these eyes.

PMID- 9002132
TI  - Remodelling of choroidal circulation in carotid cavernous sinus fistula.
AB  - BACKGROUND: Carotid cavernous sinus fistula may induce drastic changes in
      choroidal circulation secondary to elevated orbital venous pressure. CASES AND
      METHODS: Three patients affected by spontaneous carotid cavernous sinus fistula
      were studied for 3-15 months. The angioarchitecture and hemodynamics of the
      choroid were evaluated repeatedly by indocyanine green angiography using a
      montage panoramic technique. RESULTS: Choroidal vessels underwent drastic
      restructuring including patchy nonperfusion of the choriocapillaris, attenuation
      of vortex veins, preferential venous dilatations, and drainage into outflow
      channels near the optic disc or into anterior ciliary veins. CONCLUSIONS:
      Choroidal veins were very versatile in remodelling their structure and
      hemodynamics after sustained elevation of orbital venous pressure. The presence
      of numerous anastomoses between choroidal veins appeared to be a major underlying
      cause of this versatility. The observed remodelling of choroidal vessels seemed
      to be guided by the principle that the venous blood flowed toward sites of lesser
      pressure resistance.

PMID- 9002133
TI  - Long-term follow-up of chronic Lyme neuroretinitis.
AB  - PURPOSE: The authors report sequential fluorescein angiographic and color
      photographic findings of the fundi and response to treatment in a patient with
      chronic Lyme neuroretinitis. METHODS: A Lyme enzyme-linked immunosorbent assay
      with purified 41-kd flagellin as antigen was used to detect immunoglobulin G and
      immunoglobulin M antibodies to Borrelia burgdorferi in serum, cerebrospinal
      fluid, and vitreous. The changes were documented by fluorescein angiography and
      color photography tests performed during a 5 1/2 year follow-up. RESULTS: The
      diagnosis of Lyme neuroretinitis was based on the history of erythema migrans and
      positive Lyme enzyme-linked immunosorbent assay tests from cerebrospinal fluid
      and vitreous and by the exclusion of other infectious and systemic diseases and
      uveitis entities. Fluorescein angiography results disclosed bilateral chronic
      neuroretinal edema with areas of cystoid, patchy, and diffuse hyperfluorescence
      peripapillary and in the macular areas. The hyperfluorescent lesions enlarged
      despite a 9-month period of antibiotic therapy. CONCLUSION: Lyme borreliosis may
      cause neuroretinitis with unusual angiographic findings. Chronic Lyme
      neuroretinitis may be unresponsive to antibiotic therapy.

PMID- 9002134
TI  - Retinal vascular nonperfusion and retinal neovascularization as a consequence of
      cytomegalovirus retinitis and cryptococcal choroiditis.
AB  - BACKGROUND: Cytomegalovirus retinitis and cryptococcal choroiditis are
      opportunistic infections in patients with acquired immune deficiency syndrome.
      These infections are associated with a retinal vasculitis and vascular
      attenuation. METHODS: We present a case of retinal vascular nonperfusion and
      retinal neovascularization in a patient with acquired immune deficiency syndrome.
      RESULTS: Retinal vascular nonperfusion and retinal neovascularization were
      confirmed by fluorescein angiography. CONCLUSIONS: This is the first reported
      case of retinal neovascularization in a patient with acquired immune deficiency
      syndrome, ocular cytomegalovirus retinitis, and cryptococcal infection.

PMID- 9002135
TI  - Doppler ultrasonography of the central retinal artery by duplex scanning.
AB  - PURPOSE: To present duplex scanning of the central retinal artery, which the
      authors have termed duplex scanner imaging, as an alternative to color Doppler
      imaging in the evaluation of retinal blood flow velocity, and to show the
      difference in measurements obtained with the two different techniques. METHODS:
      The high-resolution ATL-Ultramark 4 duplex scanner (Advanced Technology
      Laboratories, Bothell, WA) with the variable focus access probe was used to
      measure blood flow velocity of the central retinal artery in the eyes of 48
      healthy volunteers. RESULTS: Using this technique the peak systolic flow velocity
      (+/- standard deviation [SD]) of the central retinal artery was 36.6 +/- 10.8
      cm/sec, and the end diastolic flow velocity was 12.6 +/- 3.7 cm/sec. CONCLUSION:
      The flow velocity measurements of the central retinal artery obtained with this
      technique were much higher than those obtained by other authors using color
      Doppler imaging (9.6 cm/sec for the peak systolic flow velocity, and 4.7 cm/sec
      for the end diastolic flow velocity). The authors propose duplex scanner imaging
      as an alternative to color Doppler imaging for evaluating retinal blood flow
      velocity. The duplex scanner also can be used to measure the flow velocity of
      orbital vessels.

PMID- 9002136
TI  - The use of intravitreal tissue plasminogen activator in the treatment of
      experimental subretinal hemorrhage in the pig model.
AB  - PURPOSE: To clinically and surgically evaluate clot lysis in an animal model of
      subretinal hemorrhage after intravitreal injection of tissue plasminogen
      activator. METHODS: Autologous subretinal hemorrhages were created via a
      transvitreal approach in 18 pigs. The next day (day 1) animals were randomly
      selected to receive either an intravitreal injection of 0.1 mL balanced salt
      solution or 0.1 mL tissue plasminogen activator (25 micrograms) followed by
      observation or vitrectomy a day later. On day 2, six pigs (all treated with
      tissue plasminogen activator) underwent a vitrectomy in which aspiration of the
      subretinal hemorrhage was attempted. The other eyes were evaluated for clot lysis
      by ophthalmoscopy at days 3, 10, and 30. All eyes were examined
      histopathologically. RESULTS: The eyes that had been treated with tissue
      plasminogen activator demonstrated a color change at the peripheral margin, which
      suggested that clot lysis had occurred. At the time of the vitrectomy, the clots
      were liquefied partially; removal by aspiration alone, however, was not possible.
      Photoreceptor damage was moderate to severe by day 10 in all eyes, whether they
      were treated with tissue plasminogen activator or balanced salt solution. All
      eyes that underwent vitrectomy had moderate to severe photoreceptor damage.
      CONCLUSIONS: In this animal model, intravitreal tissue plasminogen activator was
      associated with features that suggested partial clot lysis; tissue plasminogen
      activator did not produce sufficient lysis to allow surgical removal by
      aspiration alone, however.

PMID- 9002137
TI  - Sensitivity and predictability of vitreous cytology, biopsy, and membrane filter
      culture in endophthalmitis.
AB  - PURPOSE: Forty-seven consecutive patients with endophthalmitis were prospectively
      studied to: 1) compare the undiluted vitreous biopsy culture and membrane filter
      culture of vitrectomy cassette fluid; 2) determine the sensitivity and
      specificity of initial smear examinations in relation to final culture; and 3)
      characterize vitreous cytology in culture positive and negative endophthalmitis.
      METHODS: Examinations included smears (Gram stains, Diff Quik [Bacto Laboratories
      Pvt. Ltd., Liverpool, Australia] and unstained) and aerobic/anaerobic culture of
      undiluted vitreous biopsy specimens and diluted vitreous collected in the
      cassette. The cassette fluid was passed through 5-microns polycarbonate filter
      for cytology and a 0.22-microns polyvinylidene difluoride millipore filter for
      culture. RESULTS: By either method culture results were positive in 27 (57.4%)
      patients. Culture positive of the vitreous biopsy alone was 44.6% and cassette
      fluid alone was 49% (P > 0.05). In the initial smear examination the sensitivity
      and specificity of the Gram stain were 66.6% and 84.2%, respectively.
      comparatively, Diff Quik provided lower sensitivity and specificity at 40.7% and
      80.9% respectively. Examination of wet film of vitreous samples did not provide
      any useful information. Although polymorphs were seen in large numbers in all
      cultures that yielded positive results on examination, they also were seen in 80%
      of the sterile samples. There was no significant difference in the quantity of
      macrophages observed in infected and noninfected samples. CONCLUSIONS: Initial
      smear examination and cytology have limited roles in the diagnosis of infectious
      endophthalmitis. Obtaining cultures of both an undiluted vitreous biopsy sample
      and the vitrectomy cassette fluid has a significant advantage compared with
      culture of only one sample.

PMID- 9002139
TI  - Diagnostic and therapeutic challenges.

PMID- 9002140
TI  - An unusual presentation of a juxtapapillary choroidal melanoma.

PMID- 9002138
TI  - The Agar sandwich technique for retinal biopsy processing.
AB  - BACKGROUND: The authors developed an agar sandwich technique for retinal biopsy
      processing. This tissue agar embedding technique allows for a rapid and reliable
      method to handle and transport retinal biopsies from the operative field to the
      histology laboratory. METHODS: Biopsies from rabbit retinas infected with herpes
      simplex virus, epiretinal membranes from patients with macular pucker, and
      retinas from patients with acute retinal necrosis were studied. Each retinal
      biopsy was fixed, mounted on an agar disc, and covered with liquid agar. Light
      microscopy, electron microscopy, immunocytochemistry, and polymerase chain
      reaction were employed on the agar-embedded tissue. RESULTS: The tissues remained
      mounted in the agar sandwich and maintained their orientation throughout the
      processing. The morphologic integrity, histologic characteristics, antigenic
      properties, and DNA quality all were preserved using the agar sandwich technique.
      CONCLUSION: The agar sandwich technique is an efficient and simple technique for
      handling small biopsy specimens that require various analyses.

PMID- 9002141
TI  - Floating vitreous cyst.

PMID- 9002142
TI  - Injuries to the central nervous system.

PMID- 9002144
TI  - Changing patterns in organ donation in Eurotransplant, 1990-1994.
AB  - Organ transplantation has become the treatment of choice for patients with end
      stage organ failure and has led to progressive increases in the size of waiting
      lists over the past decade. Unfortunately, from 1990 to 1994, the number of organ
      donors remained stable while the number of organs transplanted from these donors
      increased by only 10%. In view of the severity of the current organ shortage,
      elderly individuals are increasingly being accepted as organ donors. The graft
      survival rate with kidneys from donors older than 55 years is 5% lower than that
      with kidneys from younger donors at 1 years and 9% lower at 3 years post
      transplantation. Graft survival is also significantly lower with organs from
      donors who die from cerebrovascular accidents than it is with organs from donors
      whose cause of death is cerebral trauma. The number of patients waiting for a
      nonrenal donor organ has increased rapidly in the past 5 years, and an increasing
      number of donor kidneys are now being provided by multiorgan donors. The
      favorable graft survival rate with multiorgan donor kidneys, which is
      significantly better than that obtained with single organ donor kidneys, confirms
      their suitability for renal transplantation.

PMID- 9002143
TI  - Magnetic fields and leukemia--risk for adults living close to power lines.
AB  - The objective of this study was to investigate the risk of leukemia from magnetic
      field exposure among Finnish adults living close to high-voltage power lines. The
      cohort study included 383700 Finnish people having lived in 1970-1989 within 500
      m of overhead power lines of 110-400 kV in a magnetic field calculated to be > or
      = 0.01 microT. The nested case-cohort study was conducted to investigate dose
      response and time-related factors in further detail. Data collection was based on
      several subsequent record linkages of nationwide registers. The subjects were
      followed for cancer in 1974-1990, providing over 2.5 million person-years. The
      outcome measures included standardized incidence ratios, incidence rate ratios,
      and odds ratios for several exposure indices. The total number of leukemia cases
      was 203. Magnetic fields were not associated with the overall occurrence of
      leukemia among adults. The risk estimates were adjusted for age, gender, and
      municipality; the other covariates had no effect on the risk estimates. However,
      an almost fivefold increase with statistical significance was observed for the
      risk of chronic lymphatic leukemia in relation to earlier, or long-lasting,
      exposure to magnetic fields of > or = 0.1 microT. This finding was based on very
      small numbers. No risk increases were observed for other types of leukemia. While
      the possibility of an increase in risk at higher magnetic field levels, or in
      relation to earlier exposures, cannot be excluded on the basis of this study, the
      results suggest that typical magnetic fields of high-voltage power lines are not
      an important cause of leukemia in adults.

PMID- 9002145
TI  - Transplantation of kidneys donated from the USA: long-term results and viability
      testing using 31P-MRS.
AB  - Since June 1983, 27 kidneys have been shipped to the Kidney Center at the Tokyo
      Women's Medical College (TWMC) from the United States. These organs were divided
      into two groups, based on the years of their donation; 13 kidneys were assigned
      to group 1 and 14 to group 2. The differences between the two groups were as
      follows: donor age 19.8 +/- 10.0 years vs 51.9 +/- 14.5 years in group 2 (P <
      0.0001); total ischemic time 42 h 12 min in group 1 vs. 65 h 42 min in group 2 (P
      = 0.0002); and Euro-Collins preservation solution in group 1 vs University of
      Wisconsin (UW) solution in group 2. One hundred percent of the kidneys in group 1
      and 85.7% of those in group 2 recovered their function. The lowest serum
      creatinine levels averaged 96 +/- 38.4 mumol/l and 185.8 +/- 101.0 mumol/l,
      respectively (P = 0.01). The viability of 9 out of 14 grafts in group 2 were
      tested using 31P magnetic resonance spectroscopy (31P-MRS). The results showed
      that all of the grafts having a monophosphate/inorganic phosphate (MP/Pi) ratio
      higher than 0.3 recovered their function and those lower than 0.2 did not. The
      problems associated with international organ sharing are discussed, along with
      the difficulties encountered at TWMC.

PMID- 9002147
TI  - Nitric oxide-related neural components in the rat small intestine after
      transplantation.
AB  - The changes in nitric oxide (NO)-related neural components in the transplanted
      small intestine are unknown. In this study, the NO neural component was examined
      using electrophysiological and NADPH-diaphorase histochemical techniques in a rat
      small bowel transplantation model. Syngeneic total small bowel transplantation
      was performed in 26 male Lewis rats using microsurgical techniques. The rats were
      divided into four groups: an untreated control group and animals at 1 (G1), 2
      (G2), and 4 (G4) weeks after transplantation. Jejunal strips were mounted in a
      superfusion apparatus for examination. In the presence of atropine and
      guanethidine, the effect of the NO synthesis inhibitor L-NG-nitro-arginine (L
      NNA, 100 microM) relaxation mediated by the nonadrenergic, noncholinergic (NANC)
      neural system was assessed following electrical stimulation at 2Hz. The
      inhibitory effect of L-NNA on relaxation was taken as an indicator of NO
      production. The percentage of inhibition in the control group, and in G1, G2, and
      G4 was 43.30% +/- 6.08% (mean +/- SE), 42.10% +/- 6.69%, 43.62 +/- 10.00%, and
      52.46% +/- 6.00%, respectively. Inhibition in G4 was significantly higher than in
      the other groups (P < 0.01). The percentage of NADPH-diaphorase-positive fibers
      in the control group, G1, G2, and G4 was 25.06% +/- 4.70% (mean +/- SE), 26.27%
      +/- 2.17%, 24.73% +/- 2.87%, and 30.76% +/- 3.19%, respectively. Again, G4 showed
      a significantly higher level than the other groups (P < 0.01). We conclude that
      increased NO production may play a significant role in maintaining the intrinsic
      nervous system of the small intestine after transplantation.

PMID- 9002146
TI  - Rescue therapy with tacrolimus (FK 506) in renal transplant recipients--a
      Scandinavian multicenter analysis.
AB  - All renal allograft recipients (n = 32) in Sweden and Norway who were converted
      from cyclosporin (CyA)-based immunosuppression to FK 506 (tacrolimus) between
      October 1992 and June 1995 were analyzed retrospectively. The reasons for
      conversion were acute refractory rejection (n = 21), chronic rejection (n = 4),
      and suspected CyA toxicity (n = 6); one patient was converted for psychological
      reasons. The mean time from transplantation to conversion was 29 (range 1-243)
      weeks and there was a mean follow-up of 46 (2-143) weeks. Overall graft survival
      was 59%, with graft survival 52% in patients converted because of acute
      rejection, 50% in patients converted because of chronic rejection, and 83% in
      patients converted because of CyA toxicity. There was no significant correlation
      between preconversion serum creatinine and outcome. Seventy-two percent of the
      patients had significant side effects during FK 506 treatment, the most frequent
      ones being neurological and gastrointestinal symptoms. These improved after dose
      reduction. Two patients became overimmunosuppressed and developed lymphoma. One
      patient died of the primary kidney disease, hemolytic uraemic syndrome. We
      conclude that FK 506 therapy is able to salvage kidneys with acute refractory
      rejection and that it is an alternative in patients with CyA toxicity. However,
      the risk of overimmunosuppression must be considered.

PMID- 9002148
TI  - Ultrastructure changes associated with brain death in the human donor heart.
AB  - Electromicroscopic examinations were carried out on 30 myocardial biopsies taken
      from 22 human donor hearts immediately after excision (prestorage) or immediately
      before transplantation (poststorage). All electron micrographs were independently
      examined by two morphologists. Eleven structures were examined in each
      micrograph, and each structure was scored according to the degree of injury. A
      good interobserver correlation was obtained in 84% of the structures scored. In
      the prestorage left ventricular biopsies (n = 11), approximately 20%-25% showed
      moderate to severe ultrastructural injury. The ultrastructural injury observed in
      the poststorage left ventricular biopsies (n = 15) was no different from that in
      the prestorage group, particularly injury to the sarcomere and mitochondria. A
      similar degree and pattern of injury was seen in the right ventricle (n = 4).
      There was no evidence that an ischemic storage period of less than 6 h increased
      the degree of injury seen. However, there was a higher incidence of moderate to
      severe injury in those hearts excised from donors initially dependent on high
      inotropic support.

PMID- 9002149
TI  - Combined heart-lung-liver, double lung-liver, and isolated liver transplantation
      for cystic fibrosis in children.
AB  - Between June 1990 and September 1995, 8 of 24 children with cystic fibrosis (CF)
      who were accepted either for combined transplantation or isolated liver
      transplantation died while waiting for a graft; 11 underwent transplantation and
      5 are currently on the waiting list. Of the 11 children who had surgery, 7 (group
      1) underwent one of the following procedures: heart-lung-liver (n = 4),
      sequential double lung-liver (n = 2), or bilateral lobar lung from a split left
      lung and reduced liver (n = 1). During the same period, the four other children
      (group 2) underwent isolated liver transplantation (three full-size livers, one
      partial liver). There was one perioperative death in each group. Pulmonary
      infection was the most common cause of morbidity in group 1. Other complications
      in group 1 included tracheobronchial stenosis (n = 2), biliary stricture (n = 2),
      and severe ascites (n = 2). All were successfully treated. Obliterative
      bronchiolitis developed in three patients. This was treated with FK 506. In group
      2, pulmonary function tests improved or remained stable after liver
      transplantation. Surgical complications in group 2 included severe ascites (n =
      1), biliary stricture (n = 1), and abscess of the liver (n = 1). Actuarial
      survival was 85.7% +/- 2% in group 1 at 1 year; it remained unchanged at 3 years
      and was 64.2% at 5 years.

PMID- 9002151
TI  - Migration of host and donor T cells in small bowel transplantation.
AB  - In this study migration of host and donor CD4+ and CD8+ T cells in a fully
      allogeneic model was described and compared with the migration pattern in a graft
      versus-host reaction (GVHR) model, where the T-cell traffic in the graft served
      as a physiological control. Heterotopic small bowel transplantations were
      performed in a rat model, with animals being sacrificed on postoperative days
      (POD) 2, 3, 4, 5, and 7. Graft and host mesenteric lymph nodes were harvested,
      homogenized, and stained with monoclonal antibodies against MHC class I, CD4+,
      and CD8+ antigens. The host and donor T cell migration patterns were studied
      using a double-staining flow cytometric technique. We found that during the
      development of rejection, the normal physiological circulation of graft and host
      T cells was disrupted. In the graft of the allogeneic model, a shift from host
      cell to graft cell dominance occurred on POD 3-4. This change in migration
      pattern coincided in the host with a 6% peak in graft cell infiltration, which
      disappeared on POD 7. These patterns of T-cell migration may be further explored
      for diagnostic purposes.

PMID- 9002150
TI  - Selective treatment of early acute rejection after liver transplantation: effects
      on liver, infection rate, and outcome.
AB  - To evaluate the results of selective treatment of biopsy-proven mild acute
      rejection episodes, we retrospectively studied 1-week liver biopsies of 103
      patients with a primary liver graft in relation to liver function tests. The
      overall incidence of rejection was 35%. In four patients the biopsy showed
      histological features consistent with rejection; in 27 patients it showed mild
      acute rejection (grade 1), and in 5 patients it showed moderate acute rejection
      (grade 2). Study group 1 consisted of 19 untreated patients with grade 1
      rejection and group 2 of 8 treated patients with grade 1 rejection. At 30 and 90
      days, no differences in liver function tests were found. The infection rate,
      histology after 1 year, and survival in the two groups did not differ. It may,
      therefore, be concluded that withholding treatment in histologically proven mild
      acute rejection is possible in selected patients based on histological,
      biochemical, and clinical criteria. This may reflect the functional diversity of
      morphologically similar lymphocytic infiltrates observed in graft biopsies
      showing features of mild acute rejection.

PMID- 9002152
TI  - Rescue therapy with tacrolimus in simultaneous pancreas/kidney transplantation.
AB  - Tacrolimus has been effective both in primary and rescue therapy following
      steroid and OKT3-resistant acute rejection in liver and kidney transplantation.
      Due to the effects of tacrolimus on glucose metabolism, there has been concern
      about its use in simultaneous pancreas/kidney transplantation. We report on the
      results of six patients (three female, three male, age 35.2 +/- 7.3 years)
      converted from cyclosporin A to tacrolimus following simultaneous pancreas/kidney
      transplantation in steroid-resistant acute rejection. Tacrolimus was induced 2.8
      +/- 1.7 months (range 1-4.8 months) after transplantation; follow-up was 3-18
      months. Following conversion, creatinine levels declined in all patients [3.5 +/-
      1.2 mg/dl before conversion, 3.0 +/- 1.9 mg/dl (n = 6) at three months, 1.4 +/-
      0.1 mg/ dl at 1 year (n = 3)]. Before conversion, fasting blood glucose levels
      averaged 154 +/- 33 mg/dl, with three patients receiving insulin. Three months
      later no patient required insulin, the mean glucose level being 107 +/- 23 mg/dl
      (n = 6); at 1 year it was 92 +/- 9 mg/dl (n = 3). One patient lost his pancreatic
      graft after 4 months due to a mycotic aneurysm. We conclude that conversion to
      tacrolimus is a safe and effective treatment in cases of steroid-resistant
      rejections following pancreas/ kidney transplantation.

PMID- 9002153
TI  - Liver transplantation for fulminant hepatic failure: importance of renal failure.
AB  - One hundred eighty-one consecutive patients with fulminant hepatic failure (FHF)
      presenting in a 2-year period were reviewed. In this cohort we examined the
      impact of pretransplant renal failure on mortality and morbidity following
      orthotopic liver transplantation (OLTx). Twenty-seven patients (18 female, 9
      male) with a median age of 43.5 years (range 19-65 years) underwent OLTx. FHF was
      due to idiosyncratic drug reaction (n = 4), paracetamol overdose (n = 3),
      seronegative hepatitis (n = 17), hepatitis B (n = 1), veno-occlusive disease (n =
      1), and Wilson's disease (n = 1). Renal failure was present in 14 patients, 7 of
      whom died (whereas there was 100% survival in patients without renal failure).
      Pretransplant renal failure was associated with prolonged mechanical ventilation
      (13 days vs 6 days, P = 0.05), prolonged intensive care stay (17 days vs 8 days,
      P = 0.01) and prolonged hospital stay (27 vs 21 days, P = NS). Pretransplant
      renal failure did not predict renal dysfunction at 1 year after OLTx. We conclude
      that the survival of patients transplanted for FHF is inferior to that of
      patients transplanted for chronic liver disease (67% vs 88% 1-year survival in
      Birmingham). For patients with FHF undergoing transplantation, pretransplant
      renal failure strongly predicts poor outcome with significantly greater
      consumption of resources.

PMID- 9002154
TI  - Disseminated angiosarcoma presenting as a hemophagocytic syndrome in a renal
      allograft recipient.
AB  - A case of angiosarcoma arising in the setting of transplantation is reported.
      This rare and malignant tumor of the endothelial system is seldom observed in
      allograft recipients, with only seven cases having been previously reported. What
      is interesting about the present observation is that the tumor is thought to have
      developed in the vicinity of a Dacron graft and that it showed prominent
      erythrophagocyte-like activity. This activity was associated with a particular
      clinical syndrome that shared some attributes with infection-associated
      hemophagocytic syndrome.

PMID- 9002155
TI  - Late ureteral obstruction after kidney transplantation. Fibrotic answer to
      previous rejection?
AB  - Today, the incidence of urological complications following renal transplantation
      is 2%-10%. Most of these complications occur within the 1st year and affect the
      distal ureter. We report on two patients who developed very late ureteral
      obstruction, 14 and 18 years after transplantation. Both patients had rejection
      episodes 1 and 10 months prior to the ureteral stenosis. Histological examination
      of one resected ureter revealed findings strongly suggestive of a rejection
      process. Open surgery with antirefluxive reimplantation into the bladder was
      successful in both patients, with a postoperative observation time of 20 and 8
      months, respectively. We conclude that a percutaneous nephrostomy may be required
      in patients with rising creatinine and incipient hydronephrosis even long after
      transplantation has been performed.

PMID- 9002156
TI  - Hyperacute renal allograft rejection from anti-HLA class 1 antibody to B cells-
      antibody detection by two color FCXM was possible only after using pronase
      digested donor lymphocytes.
AB  - We present a report of a transplant recipient who lost her renal allograft from
      hyperacute rejection. This was secondary to a weak IgG anti-HLA class I antibody
      that was only reactive to donor B lymphocytes. This antibody was not detected in
      her pretransplant serum by the conventional complement-dependent cytotoxicity
      assays using donor blood lymphocytes. Pretransplant sera were analyzed
      retrospectively by two-color flow cytometric crossmatching (FCXM). It was
      difficult to determine if the recipient's serum contained an IgG antibody
      specific for HLA on donor B cells since IgG from control AB sera and
      pretransplant sera bound equally well to CD19 B cells. However, when donor
      lymphocytes were pretreated with pronase to digest the membrane receptor for Fc
      domain of IgG (Fc gamma R) on non-T-cells, control IgG in AB serum did not bind
      to B cells and, hence, it was easy to detect binding of IgG (in pretransplant
      sera) to HLA on B cells. This case underscores the importance of identifying weak
      anti-HLA class I antibodies reactive only to B cells. Moreover, it shows that the
      currently used two-color FCXM lacks the specificity to detect such antibodies.

PMID- 9002157
TI  - Intraoperative measurement of graft blood flow--a necessity in liver
      transplantation.
AB  - Portal venous and hepatic arterial flow was measured intraoperatively in the 70
      most recent patients undergoing liver transplantation in our institution.
      Impaired graft flow due to vascular abnormalities was detected in six patients.
      One patient suffered from arterial steal due to stenosis of the recipient celiac
      trunk with blood shunting from the hepatic to the splenic artery. Ligation of the
      recipient hepatic artery restored the arterial graft flow. In two patients we
      found reduced portal venous flow due to large portosystemic collaterals. The
      collaterals accountable for the impaired portal flow were identified and ligated,
      which restored portal venous graft flow. Excessive sensitivity of the portal
      venous flow to the position of the graft was found in a 6-month-old boy. Portal
      venous flow varied considerably, depending upon the position of the graft, and
      intraoperative flow measurement allowed the best position of the graft to be
      identified. Two patients developed arterial thrombosis in the early postoperative
      course. Immediate laparatomy with thrombectomy resulted in good, palpable
      pulsation in the graft artery in both patients. Intraoperative flow measurement
      demonstrated satisfactory arterial flow in one patient, whereas there was no net
      flow in the other patient's graft artery. Pulsation in this patient was caused by
      blood oscillating in and out of the liver. In conclusion, we find that causes of
      primary graft dysfunction due to technically flawed reperfusion of the graft can
      be identified and alleviated by intraoperative measurement of the flow in the
      graft vessels.

PMID- 9002158
TI  - A trial of high-dose ursodeoxycholic acid therapy in a liver transplant
      recipient.

PMID- 9002160
TI  - Malignancy transplantation with graft: do patients with primary central nervous
      system tumors have to be excluded from the donor pool?

PMID- 9002159
TI  - HHV-8 is associated with recurrent Kaposi's sarcoma in a renal transplant
      recipient.

PMID- 9002161
TI  - Esthesioneuroblastoma developing in a kidney transplant recipient.

PMID- 9002162
TI  - History of veterinary radiation oncology.
AB  - The history of veterinary radiation oncology is reviewed from 1895 to the
      present. The field was very slow to develop from the early 1900s to the 1980s.
      Rapid progress is now being made with much greater interest on the part of the
      companion animal-owning public for more advanced treatment of various diseases.
      The number of veterinary radiation oncologists and the number of well-equipped
      radiation therapy centers are increasing.

PMID- 9002163
TI  - A selected review of the physics of radiation therapy.
AB  - This article covers some of the basic physics needed to understand and plan
      radiation therapy. Special attention is given to those issues that are more
      common in veterinary radiation oncology. Far greater depth of discussion and
      explanation may be found in many standard texts and should be used for specific
      information and situations.

PMID- 9002164
TI  - Biologic basis of radiation therapy.
AB  - The biologic effects of ionizing radiation are well understood. The limitations
      of radiation therapy time-dose schemes typically used in veterinary medicine are
      also well understood. Before expensive and potentially toxic combinations of
      treatment, such as radiation combined with chemotherapy or radiation combined
      with hyperthermia, can be fully understood, the effect of optimizing the manner
      in which radiation itself is administered must first be defined. This will only
      occur after a sufficient period of observation after improvement of the radiation
      time-dose schemes in use today. Also, when evaluating historic data regarding the
      response of canine and feline tumors to irradiation, the time-dose scheme used
      must be considered. Many papers were published based on coarsely fractionated
      schemes using large doses per fraction and relatively low total doses. Thus, the
      response rates published must be tempered by the fact that it may be possible to
      obtain better tumor control rates using smaller doses per fraction and a larger
      total dose.

PMID- 9002165
TI  - Radiation therapy toxicities.
AB  - Since the infancy of radiology and radiation therapy, reactions to radiation have
      been noted and followed, and attempts have been made to minimize these reactions.
      We have turned to radiobiologists to explain these reactions and to radiation
      oncologists to prevent or decrease the normal tissue effects of radiation
      therapy. Radiation toxicities are divided into early (acute) and late (chronic)
      reactions; however, it is important to note that severe toxicities are rare and
      occur typically in less than 5% of veterinary radiation therapy patients.

PMID- 9002166
TI  - Radioresistance, chemoresistance, and apoptosis resistance. The past, present,
      and future.
AB  - A wide variety of cancer therapy resistance mechanisms are available, with
      perhaps surprising overlap between causes of chemotherapy and radiation
      resistance. As previously discussed, most of the widely used chemotherapeutic
      agents and gamma-radiation utilize apoptosis as the common death pathway, thereby
      making apoptosis and the ability to manipulate apoptosis of integral importance
      to the future of cancer therapy. This is evidenced by the information explosion
      on this topic in the last 5 years. Obviously much remains to be learned. However,
      with the aforementioned cooperation of the oncology team and a greater
      understanding of the molecular mechanisms behind cancer and cancer therapy
      resistance, response rates, survival times, the quality of life of patients
      enduring antineoplastic therapies, and the importance of comparative oncology can
      only increase. We look forward to the findings in the coming years on this
      incredibly clinically relevant topic with great fondness and uncertainty.

PMID- 9002167
TI  - Interstitial implant brachytherapy in small animals.
AB  - This article presents highlights of the physics, implantation technique, and
      clinical application of iridium-192 interstitial implant brachytherapy. Some of
      the physical differences between iridium-192 brachytherapy and cobalt-60
      teletherapy are compared.

PMID- 9002168
TI  - Tumors of the skin and associated structures.
AB  - Because of the location of skin tumors, afflicted dogs and cats are frequently
      presented to veterinarians for examination. The location also facilitates the use
      of radiation therapy for patients with skin tumors. Few animals treated with
      radiation therapy for skin tumors experience significant toxicity. Animals with a
      variety of skin tumors can benefit from treatment with radiation therapy. These
      tumors include mast cell tumors, squamous cell carcinoma, tumors of the digit,
      tumors of the ear canal, tumors of the cutaneous adnexa, mammary gland tumors,
      plasma cell tumors, cutaneous melanoma, cutaneous hemangiosarcoma, and
      transmissible venereal tumors. The prognosis for individual patients varies with
      the tumor type and, in some cases, with the stage of the disease.

PMID- 9002169
TI  - Neuroradiation oncology.
AB  - Neuroradiation oncology is a subdiscipline that is rapidly developing in
      veterinary practice. This article reviews the literature and emphasizes the
      positive results that are being achieved with better techniques and higher doses.

PMID- 9002170
TI  - Radiation oncology of head and neck tumors.
AB  - Malignant tumors of the head and neck region occur commonly in veterinary
      medicine. Unfortunately, tumors in the head and neck can cause treatment dilemmas
      because many neoplastic entities at this site are locally aggressive. Additional
      local therapies such as radiation therapy are becoming commonplace as
      standardized therapies for many head and neck tumors in veterinary medicine.

PMID- 9002171
TI  - The role of radiotherapy in the treatment of lymphoma and thymoma.
AB  - Chemotherapy is the mainstay of therapy for the treatment of lymphoma in dogs and
      cats. Radiation therapy can be utilized in the management of patients with
      solitary lymphoma and to induce a rapid local response in selected patients with
      multicentric lymphoma. A combination of surgery and radiation therapy can offer
      an excellent prognosis for cats with thymoma. Radiation therapy can also play a
      role in the management of dogs with thymoma.

PMID- 9002172
TI  - Radiation therapy in the management of bone tumors.
AB  - Radiation therapy is used in the management of both primary and metastatic bone
      tumors. The most common primary bone tumor in dogs and cats is osteosarcoma of
      the appendicular skeleton. A number of other primary bone tumors occur at a much
      lower rate in both species and include chondrosarcoma, fibrosarcoma,
      hemangiosarcoma, multiple myeloma, and lymphoma. This article reviews the results
      of published reports on the utility of radiation therapy in the treatment of
      primary and metastatic bone tumors of companion animals.

PMID- 9002173
TI  - Soft tissue sarcomas.
AB  - The soft tissue sarcomas (STS) constitute approximately 15% of all canine and 7%
      of all feline skin and subcutaneous tumors. STS are tumors that arise from a
      variety of mesenchymal tissues. The aggressive nature of STS in cats, especially
      those tumors occurring after vaccination, suggests that novel therapies should be
      investigated.

PMID- 9002174
TI  - Palliative radiotherapy.
AB  - Palliative radiation therapy can be useful in controlling the pain associated
      with tumors for which definitive therapy is not an option. The patient's quality
      of life is improved while side effects, hospitalization, and cost of treatment
      are minimized. Palliative radiation therapy should be considered as part of the
      oncologist's armamentarium; however, further investigations are warranted to
      develop appropriate protocols based on patient response.

PMID- 9002175
TI  - Future of veterinary radiation oncology.
AB  - Rapid developments in technology will have a profound effect on veterinary
      radiation oncology. These developments include computer-enhanced, three
      dimensional treatment planning and smaller, more compact, more reliable radiation
      equipment, primarily linear accelerators. For treatment of all veterinary
      patients, the linear accelerators need electron capability. Although fractionated
      therapy will remain the standard from of treatment, new modalities, including a
      highly precise single-dose treatment called radiosurgery, and a precise
      fractionated therapy called conformal therapy, will be utilized more in the
      future.

PMID- 9002176
TI  - Biogenic amines in Spanish beers: differences among breweries.
AB  - Ten biogenic amines in Spanish beers were studied using HPLC, Agmatine, tyramine
      and putrescine were the prevailing amines, while histamine, beta
      phenylethylamine, tryptamine, cadaverine, spermine and spermidine were detected
      at relatively low levels (in general < 2 mg/l). On the basis of the wide range of
      levels observed for tyramine (from 1.90 to 31.55 mg/l), the consumption of beer
      requires restriction in patients receiving monoamine oxidase inhibitor drugs.
      Biogenic amine levels in beers of the same type from the same company and from
      different companies were monitored every month over 1 year. Agmatine and
      putrescine levels showed minimal fluctuations in beers from the same company as
      well as from different breweries. Raw materials and brewing conditions would not
      affect the levels of those amines. However, tyramine levels were subject to wide
      fluctuations in beers produced by particular breweries irrespective of whether
      they were produced by the same company. Relatively high levels of tyramine were
      specific to some breweries.

PMID- 9002177
TI  - Quantity of K, Ca, Na, Mg, Fe, Cu, Pb, Zn and ashes in DOC Tacoronte-Acentejo
      (Canary Islands, Spain) musts and wines.
AB  - This study determines ash, K, Ca, Na, Mg, Fe, Cu, Pb, and Zn content in musts and
      wines of the DOC Tacoronte-Acentejo (Tenerife, Canary Islands) from two
      consecutive harvests. Samples were treated with HNO3 and H2O2. Na and K were
      determined by flame photometry and the remaining metals by air/acetilene flame
      atomic absorption spectrophotometry. Significant differences were observed in Na,
      Ca and Mg contents between both harvests, possibly due to climate conditions.

PMID- 9002178
TI  - Proferrorosamines and phytopathogenicity in Erwinia spp.
AB  - Proferrorosamine A (pFR A) of the plant pathogenic bacterium Erwinia rhapontici
      was shown to inhibit growth of wheat and cress seedlings at the > or = 10 ppm
      level. When the seeds were continuously exposed to 100 ppm pFR A, the germination
      of cress and wheat seeds was inhibited up to 90% and 80%, respectively. The
      inhibition could be reversed through addition of equimolar amounts of ferrous
      iron, which indicates that the strong iron chelating capability of pFR A is
      responsible for the observed effect. The Fe(II) in the corresponding iron
      complex, ferrorosamine A, was found to be remarkably resistant towards oxidation
      by hydrogen peroxide and therefore redox-cycling in the Haber-Weiss cycle. It is
      thus conceivable that pFR A may also attenuate the generation of reactive
      hydroxyl radicals during the resistant and would reaction. The apparent
      correlation between proferrorosamine production and virulence in erwiniae was
      further corroborated through the analysis of Erwinia persicinus, a newly
      described species. Using electrospray ionization mass spectrometry, E. persicinus
      was shown to produce pFR A and pFR B, and preliminary evidence for the
      phytopathogenicity of E. persicinus was found in cress. Inhibition of wheat
      seedlings by E. persicinus could not be demonstrated, but this may be due to
      technical difficulties or different host specificities. Taken together, our
      results indicate that the phytopathogenicity of E. rhapontici and E. persicinus
      may, as least in part, be due to the release of proferrorosamines.

PMID- 9002179
TI  - Effects of selenium and serum on selenoprotein W in cultured L8 muscle cells.
AB  - When rat L8 muscle cells were cultured to examine the effects of serum and
      selenium concentration on selenoprotein W levels and glutathione peroxidase (GPX)
      activities, no significant differences (P > 0.05) were found in selenoprotein W
      levels and GPX activities during differentiation. With three different forms of
      selenium, selenoprotein W levels and GPX activities were shown to increase in L8
      myotubes cultured in media with these selenocompounds. Selenite was utilized more
      efficiently than selenocysteine for both selenoprotein W and GPX activity, but
      selenium as selenomethionine was less available. Both the protein content and
      mRNA levels for selenoprotein W were affected by the selenium content of the
      media. Northern blot data indicated that the expression of selenoprotein W mRNA
      increased significantly when L8 myotubes were cultured with selenium (P > 0.05).
      L8 myotubes cultured in 10% calf serum (CS) versus 2% CS with or without addition
      of 10(-8) M selenium indicated that the increase of selenoprotein W level in L8
      myotubes cultured with higher serum concentration (10% CS) is due to the higher
      selenium concentration in media rather than serum itself.

PMID- 9002180
TI  - Zinc protection against cadmium-induced infertility in female rats. Effect of
      zinc and cadmium on the progesterone production of cultured granulosa cells.
AB  - Adult female rats were treated subcutaneously (s.c.) with zinc chloride (ZnCl2,
      10 or 20 mg kg-1 body weight, bw) four times during two ovarian cycles. The third
      injection was accompanied by cadmium chloride (CdCl2) administration sc (2.5, 5
      and 10 mg kg-1 bw). The fourth zinc (Zn) treatment was followed by mating. ZnCl2
      (20 mg kg-1) itself impaired fertility by 20%, while CdCl2 dose-dependently
      blocked the receptivity of female rats. In combination with 2.5 and 5 mg kg-1
      CdCl2 the metal salts decreased fertility in an additive fashion, whereas at the
      highest CdCl2 dose (10 mg kg-1) a marked ameliorating effect of ZnCl2 (10 and 20
      mg kg-1) on cadmium (Cd)-caused sterility was observed. In the pregnant animals
      apart from the higher Cd-induced blood progesterone levels and reduced body
      weight gain of dams, no significant treatment-related maternal and fetal effects
      could be observed. ZnCl2 (10 to 80 microM) and CdCl2 (10 to 80 microM) were added
      to the culture medium of ovarian granulosa cells. CdCl2 suppressed follicle
      stimulating-hormone- (FSH-) and cAMP-stimulated progesterone accumulation. No
      protective effect of Zn against Cd-induced drop in progesterone production could
      be seen, while Zn by itself induced a significant increase in FSH-supported
      progesterone synthesis. In conclusion, while Zn protected against Cd-induced
      sterility in vivo, it failed to counteract the direct effect of Cd on steroid
      biosynthesis. The data indicate that Zn protection does not take place at the
      level of ovary. Moreover, Zn and Cd seem to affect FSH-stimulated progesterone
      production by different mechanisms.

PMID- 9002181
TI  - The chirality selectivity in the uptake of platinum (II) complexes with 1,2
      cyclohexanediamine isomers as carrier ligand by human erythrocytes.
AB  - The uptake kinetics of cisplatin analogs of 1,2-cyclohexanediamine(dach) isomers
      with various leaving groups, by human erythrocytes in plasma isotonic buffer,
      were studied. The experimental results showed that the uptake rate constants (k
      values) decrease with the change of leaving group in the sequence: chloride (Cl)
      > squaric acid (SA) > oxalate (OX) > demethylcantharic acid (DA), with the same
      dach isomer as carrier group. It is noteworthy that for the platinum (II)
      complexes with the same leaving group, the k values always reduce as: 1R, 2R-dach
      > 1R, 2S-dach > 1S, 2S-dach. This result reflects the chirality selectivity. No
      differences in reactivity to protein thiols and effects on membrane permeability
      were found for the R,R-, R,S-, S,S-isomeric complexes. It is proposed that the
      chirality selectivity in uptake is due to the recognition of the chirality of the
      platinum complexes by the erythrocyte membrane. The interactions between the
      chiral platinum complexes and the head groups of the membrane phospholipid
      molecules are probably involved.

PMID- 9002182
TI  - Synthesis of octyl O- and S-glycosides related to the GPI anchor of Trypanosoma
      brucei and their in vitro galactosylation by trypanosomal alpha
      galactosyltransferases.
AB  - Octyl O- and S-glycosides of mono- to tri-saccharides related to the core
      structure alpha-D-Manp-(1-->2)-alpha-D-Manp-(1-->6)-alpha-D-Manp of the GPI
      anchor of Trypanosoma brucei have been prepared via regioselective
      protodesilylation and glycodesilylation of octyl O- and S-glycosides of 2-O
      benzoyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1, 3-diyl)-alpha-D
      mannopyranoside. The synthetic saccharides have been used as substrates for
      enzymatic alpha-galactosylation with membrane fractions of bloodstream forms of
      T. brucei strain 427 variants MITat 1.4, MITat 1.2, and MITat 1.5, respectively.

PMID- 9002184
TI  - Conversion of p-methoxyphenyl glycosides into the corresponding glycosyl
      chlorides and bromides, and into thiophenyl glycosides.
AB  - p-Methoxyphenyl (pMP) beta-D-glycopyranosides (Glc, Gal, GlcNPhth, GalNPhth,
      GlcNTroc, Gal beta 4Glc, Gal alpha 4Gal) were prepared from the corresponding 1-O
      acetyl sugars in 79-90% yield, using boron trifluoride etherate as promoter.
      Treatment of the pMP glycosides with acyl chlorides or bromides in the presence
      of various Lewis acids gave the corresponding glycosyl chlorides and bromides in
      81-98% yield. Treatment of the acyl-protected pMP glycosides with thiophenol and
      boron trifluoride etherate gave the corresponding thioglycosides in 80-100% yield
      and high (> 20:1) beta/alpha selectivity. The stability of pMP glycosides was
      investigated against a series of reagents.

PMID- 9002183
TI  - Stereocontrolled syntheses of O-glycans of core class 2 with a linear tetrameric
      lactosamine chain and with three lactosamine branches.
AB  - Synthetic routes to O-glycans of core class 2 with a linearly extended
      tetralactosamine moiety and with three lactosamine branches are discussed. By a
      glycosyl fluoride-method, the mono- and the di-lactosaminyl units were attached
      to the core disaccharide (Gal beta 1-->3GalN3) derivatives in high
      stereoselectivity.

PMID- 9002185
TI  - Synthesis of O-glycopyranosyl heterocyclic ketene aminals and their use as
      glycosyl donors.
AB  - The synthesis and reactions of glycopyranosyl heterocyclic ketene aminals were
      investigated. Under mild conditions, the benzoyl-substituted heterocyclic ketene
      aminals 3 or 4 underwent O-glycosylation with tetra-O-acetyl-alpha-D
      glucopyranosyl bromide (1) using mercuric cyanide or silver
      trifluoromethanesulfonate as catalyst in acetonitrile to give O-glycopyranosyl
      heterocyclic ketene aminals 5-7 and 8-11, respectively. The beta-anomers were the
      sole products. By the O-glycosylation of heterocyclic ketene aminals with 1, the
      O-attack of heterocyclic ketene aminals was carried out for the first time. Some
      of 5-11 in the synthesis of oligosaccharides 14 and 15 can provide a valuable
      leaving group at the anomeric position of the glycopyranosyl ring. Compounds 6c
      or 10c may be potentially useful as glycosyl donors in the synthesis of
      oligosaccharides.

PMID- 9002186
TI  - Structure of the cyclic glucan produced from amylopectin by Bacillus
      stearothermophilus branching enzyme.
AB  - The thermostable branching enzyme (BE, EC 2.4.1.18) from Bacillus
      stearothermophilus TRBE14 produces large cyclic glucans from waxy rice
      amylopectin similar to those obtained from amylose as described elsewhere [H.
      Takata, T. Takaha, S. Okada. M. Takagi, and T. Imanaka, J. Bacteriol., 178 (1996)
      1600-1606]. The structure of the product (P-1) from the late-stage reaction was
      analyzed in detail. The weight-average degree of polymerization (dpw) of P-1 was
      900. Its chain-length distribution was not significantly changed compared with
      that of amylopectin, although the amount of long chains (dp > 38) was slightly
      decreased. The cyclic component of P-1, which was isolated by the extensive
      action of glucoamylase, had dpw of 49. Three point five alpha-1,6 linkages were
      directly involved in the formation of the ring structure with several non-cyclic
      side chains linked to the ring. Based on these results, the action and new roles
      of BE are discussed.

PMID- 9002188
TI  - Structure of the O-specific polysaccharide of Hafnia alvei PCM 1222 containing 2
      aminoethyl phosphate.
AB  - The O-specific polysaccharide of H. alvei strain PCM 1222 has a branched
      hexasaccharide repeating unit containing D-galactose, L-rhamnose, D-ribose, D
      galacturonic acid, and 2-acetamido-2-deoxy-D-glucose in the ratios 1:2:1:1:1, as
      well as 2-aminoethyl phosphate (EtNP) and O-acetyl groups in nonstoichiometric
      amounts. The polysaccharide was modified by carboxyl reduction, O-deacetylation,
      and dephosphorylation with 48% hydrofluoric acid, the last reaction being
      accompanied by removal of the lateral residue of beta-galactofuranose. The
      modified polysaccharides were studied by methylation analysis and 1H and 13C NMR
      spectroscopy, including 2D correlation spectroscopy (COSY), H-detected 1H,13C and
      1H,31P heteronuclear multiple-quantum coherence (HMQC), 1D NOE, 2D rotating-frame
      NOE spectroscopy (ROESY), and 2D combined total correlation spectroscopy (TOCSY)
      and ROESY (TORO). The following structure of the O-deacetylated polysaccharide
      was established: [formula: see text] In different batches of the polysaccharide,
      the content of EtNP varied from 0.35 to 0.55 and that of the O-acetyl groups from
      0.05 to 0.4 per repeating unit. It was tentatively suggested that the O-acetyl
      group is located at position 4 of a rhamnosyl residue.

PMID- 9002187
TI  - Purification and characterization of a (1-->3)-beta-D-glucan-binding protein from
      horseshoe crab (Tachypleus tridentatus) amoebocytes.
AB  - A novel (1-->3)-beta-D-glucan-binding protein (T-GBP) has been purified from the
      amoebocyte lysate of the Japanese horseshoe crab, Tachypleus tridentatus. It is a
      basic protein (pI 9.2) which appears to be a homotetramer composed of subunits
      with an apparent mol wt of 168000 and with an amino-terminal sequence (20
      residues) KSGFILTAPKSLTLGRNNRL. T-GBP exerted an inhibitory effect on the (1-->3)
      beta-D-glucan-initiated coagulation cascade reconstituted with purified
      preparations of factor G and the proclotting enzyme from the lysate. The binding
      of (1-->3)-beta-D-glucans to T-GBP was evaluated by measuring the residual
      amidolytic activity of the clotting enzyme, the product of the coagulation
      cascade, using Boc-Leu-Gly-Arg-4-nitroanilide as the chromogenic substrate. The
      binding specificity of a wide range of (1-->3)-beta-D-glucans and other
      polysaccharides towards T-GBP was expressed by the relative inhibition (%) of the
      activation of factor G, the first protease zymogen in the pathway, which is
      activated by binding to (1-->3)-beta-D-glucans. T-GBP was found to have a high
      affinity for linear (1-->3)-beta-D-glucans, e.g. pachyman, curdlan, and
      paramylon. It was able to bind to (1-->3)-beta-D-glucans with side-chain branches
      and mixed linkage such as schizophyllan, lentinan, laminarins, yeast beta-D
      glucan, and (1-->3),(1-->4)-beta-D-glucans such as lichenin and barley beta-D
      glucan. Binding of pachyman to T-GBP was demonstrated by an enzyme-linked
      immunosorbent assay using a specific antibody (rabbit IgG) raised against T-GBP.

PMID- 9002189
TI  - The structures of oligosaccharides isolated from the lipopolysaccharide of
      Moraxella catarrhalis serotype B, strain CCUG 3292.
AB  - The oligosaccharides from the lipopolysaccharides of Moraxella catarrhalis
      serotype B, strain CCUG 3292, were isolated after mild acid hydrolysis and
      separated by high-performance anion-exchange chromatography. The structures of
      the oligosaccharides were established by fast atom bombardment mass spectrometry
      and nuclear magnetic resonance spectroscopy. It is concluded that the
      oligosaccharides comprise a mixture of mainly a nona- and a deca-saccharide.
      [formula: see text] Smaller amounts of undeca-saccharides and of truncated forms,
      namely, hexa-, hepta-, and octa-saccharides, were also detected.

PMID- 9002191
TI  - Disulfated oligosaccharides derived from tracheobronchial mucous glycoproteins of
      a patient suffering from cystic fibrosis.
AB  - Twenty novel disulfated oligosaccharides were purified in nanomolar quantities
      from tracheo-bronchial mucous glycoproteins from a patient with cystic fibrosis
      via cleavage by alkaline borohydride treatment, followed by anion-exchange
      chromatography, size-exclusion chromatography, and high-performance liquid
      chromatography (HPLC). In addition to positive ion fast-atombombardment mass
      spectrometry (FABMS), proposed structures for the resulting purified disulfated
      oligosaccharides were also based on carbohydrate permethylation analyses,
      periodate oxidation, complete sequential exoglycosidase digestion, and parallel
      analysis of desulfated products. Sulfate esters were found to reside on C-3 or C
      6 of terminal D-galactose and on C-6 of internal D-galactose or 2-acetamido-2
      deoxy-D-glucose residues. For this group of oligosaccharides, ranging in size
      from tri- to undeca-saccharides and possessing linear, di- and tri-antennary
      forms, it was also observed that sulfate esters could be located on the same or
      on different branches and that branched oligosaccharides can possess sulfate
      esters on C-3 and C-6 of different terminal galactose residues within the same
      structure.

PMID- 9002190
TI  - The structure of the exopolysaccharide produced by the halophilic Archaeon
      Haloferax mediterranei strain R4 (ATCC 33500).
AB  - The halophilic Archaeon Haloferax mediterranei exudes into the growth medium a
      high molecular weight sulfated polysaccharide. The structure of the repeating
      unit of this polymer was determined by a combination of glycose, methylation, and
      sulfate analysis, periodate oxidation, and 1D and 2D NMR spectroscopic analysis
      of the native and periodate-oxidised/reduced polysaccharides. The location of the
      sulfate group was established from the 1H and 13C NMR data. The structure of the
      repeating unit of the polysaccharide may be written as [formula: see text]

PMID- 9002192
TI  - Structure of the O-specific polysaccharide from Burkholderia vietnamiensis strain
      LMG 6998.
AB  - The putative O-specific polymer containing D-mannose and L-rhamnose was isolated
      from the lipopolysaccharide obtained from cells walls of Burkholderia
      vietnamiensis strain LMG 6998. NMR and degradative studies showed that the
      polymer has a linear trisaccharide repeating-unit of the structure shown. The
      same polymer carrying an O-acetyl group at position 3 of the 4-substituted
      mannose residue has previously been found as the O antigen in the related species
      Burkholderia cepacia serogroup J. [formula: see text]

PMID- 9002193
TI  - Synthesis and NMR assignment of two repeating units (decasaccharide) of the type
      III group B Streptococcus capsular polysaccharide and its 13C-labeled and N
      propionyl substituted sialic acid analogues.
AB  - For the purpose of carrying out a comprehensive investigation into the nature of
      the conformational epitope of the type III group B Streptococcus polysaccharide,
      combined chemical and enzymatic methods were applied to the synthesis of three
      decasaccharide probes, namely beta-D-Glc-(1-->6)[alpha-NeuR-(2-->3)-beta-D-Gal-(1
      ->4)] -beta-D-GlcNAc-(1-->3)-beta-D-Gal-(1-->4)-beta-D- Glc-(1-->6)[alpha-NeuR-(2
      ->3)-beta-D-Gal-(1-->4)]-beta-D-GlcNAc-( 1-->3) -beta-D-Gal-OMe (22 NeuR = NeuAc;
      23 NeuR = NeuAc with 8% 13C-labeling; 24 NeuR = NeuPr). The precursor core
      octasaccharide 21 was chemically synthesized from trisaccharide donor 11 and
      pentasaccharide acceptor 19 by block condensation. Sialylation of 21 with alpha
      (2-->3)-sialyltransferase and CMP-NeuAc afforded 22. In the presence of CMP
      sialic acid synthetase and alpha-(2-->3)-sialyltransferase, 21 was sialylated
      with sialic acid derivatives (8% 13C-labeled, or N-propionyl substituted) to give
      23 and 24, respectively. Complete assignments of the 1H and 13C NMR spectra of
      compounds 21, 22 (23), and 24 are also presented.

PMID- 9002194
TI  - Isolation and characterization of an amino sugar-rich glycopeptide from the
      surface layer glycoprotein of Thermoanaerobacterium thermosaccharolyticum E207
      71.

PMID- 9002195
TI  - Immunosensors for clinical diagnostics.

PMID- 9002196
TI  - Biosensors based on flow-through systems.
AB  - When combined with biosensors as the sensing element microdialysis and flow
      injection analysis (FIA) systems become sophisticated tools for handling
      analytical processes. In particular a FIA system offers a high degree of
      automation together with high reproducibility and small sample volumes, whereas
      the biosensor, allows selective and sensitive measurements of the various
      analytes. Here we describe first a miniaturised microdialysis flow-through system
      developed for glucose determination, then we focus on amperometric immunosensors
      and on microbial sensors. In the former, antibodies against low molecular weight
      environmental contaminants or against high molecular weight proteins are
      responsible for analyte detection, whereas the latter use immobilised
      microorganisms as the recognising element for monitoring water pollutants.

PMID- 9002197
TI  - Enzymatic substrate recycling electrodes.
AB  - A weak chemical signal might result in a large response when biochemically
      amplified. Enzymatic recycling of the analyte is one of the biochemical ways of
      providing an effective increase in biosensor sensitivity by several orders of
      magnitude. The enhancement of sensitivity is provided by consecutive consumption
      and generation of the analyte on the sensor surface. The principle of enzymatic
      substrate regeneration using bioelectrocatalysis and coupled enzymes is shortly
      reviewed and illustrated with some recent developments of biosensors for
      catecholamines, and its potential for electrochemical immunoassays is outlined.

PMID- 9002198
TI  - Thermistor-based biosensing.
AB  - In this review a universal thermistor-based biosensor system is described with
      examples from clinical chemistry, bioprocess monitoring and environmental
      control. The technique is based on the measurement of the small temperature
      changes associated with enzymatic reactions occurring in a microreactor with
      immobilized enzyme. The system has good operational stability and a sensitivity
      that permits measurements down to 1 microM concentrations. Current developments
      include devices constructed by micromachining for multisensing purposes and
      miniaturised instrumentation intended for use in portable monitoring. With use of
      special supports for enzyme immobilisation even untreated whole blood samples can
      be applied. Another current line of investigation involves hybrid biosensors,
      such as combinations of electrochemistry and calorimetry into
      bioelectrocalorimetric devices with interesting new properties.

PMID- 9002199
TI  - New biosensors for environmental analysis.
AB  - Environmental analysis requires fast and reliable measurement results.
      Biosensors, which facilitate integral monitoring as well as single substance
      analysis, achieve high sensitivities in a minimum of measuring time. Four new on
      line biosensors, which cover a wide range of environmentally relevant substances,
      are introduced: A water-quality monitoring bacteria electrode, whose gradual
      development is described as an example, a heavy-metal screening urease inhibition
      sensor, a genotoxic potential as well as a immunotoxic potential indicating
      sensor. Future prospects are given.

PMID- 9002200
TI  - Biosensors for food analysis.
AB  - Concerning speed, cost and on-line capabilities, biosensors offer attractive
      alternatives to existing methods for food analysis. They make monitoring and
      control of manufacturing processes possible. Furthermore, portable biosensors
      could be used for monitoring in manufacturing, retail and distribution of foods.
      An overview is given about existing biosensors for foodstuffs that could find
      applications in food industry.

PMID- 9002201
TI  - Challenges in the development of (bio)chemical sensors for whole blood medical
      diagnostic applications.
AB  - The following article is based on experience in research and development of
      (bio)chemical sensors for medical diagnostic applications. It is not known to the
      author if the ideas presented below are applicable in other areas of sensor R &
      D.

PMID- 9002202
TI  - Commercial biosensors for medical application.
AB  - Biosensors today are represented on the market worldwide by an increasing number
      of enzyme electrodes working in various areas of medical diagnostics, and by a
      few opto-immunosensor-based analytical systems suited for protein research in
      pharmaceutical chemistry. Enzyme electrodes for metabolites and enzyme activities
      have been commercially available for about 20 years. Such sensors are
      successfully applied in laboratory autoanalyzers, point-of-care-systems, patient
      self-monitoring disposable probes, intensive care analyzers, and for on-line
      monitoring of diabetics.

PMID- 9002203
TI  - Biosensors with modified electrodes for in vivo and ex vivo applications.
AB  - Integrated and miniaturized biosensor arrays were developed exhibiting
      outstanding performance. Biosensors with negligible sensitivity to interferences
      and high long-term stability were produced by modifying electrochemical
      transducers and utilizing photopatternable enzyme membranes. The use of
      appropriate miniaturization technology leads to mass producible devices for in
      vivo and ex vivo applications.

PMID- 9002204
TI  - Present state and frontiers in biosensorics.

PMID- 9002205
TI  - Imprinting techniques in synthetic polymers--new options for chemosensors.
AB  - Highly selective molecular recognition in synthetic polymers may be the basis for
      a new type of chemosensor. For the preparation of such polymers, a molecular
      imprinting procedure during crosslinking is used to generate, with the aid of
      template molecules, microcavities of specific shape and with a defined
      arrangement of functional groups. In this review the role of the polymer matrix
      and the type of binding site interaction is discussed in more detail. Recent
      attempts to use these polymers as the basis for chemosensors are highlighted.

PMID- 9002206
TI  - Screening and characterization of new enzymes for biosensing and analytics.
AB  - The development of new or improved analytical methods requires new enzymes.
      Screening techniques utilizing enrichment cultures and rapid assay methods
      supported by automated or miniaturized methods are useful tools to detect new
      enzyme producers. Notably, oxidoreductases are well suited for analytical
      purposes. The NAD(P)- and oxygen-independent quinoprotein dehydrogenases with a
      covalently bound redox cofactor can be used advantageously for the development of
      biosensors. Examples are given of selective enrichment methods used in screening
      for useful enzyme-producing microorganisms. Enrichment under chemostatic
      conditions proved to be successful because enzymes with a remarkably high
      affinity against the analyte could be obtained. This is demonstrated by the
      screening of a trimethylamine-converting enzyme. The frequently observed high
      selectivity of these enzymes against the substrate is demonstrated in a few
      examples. In exploitation of these new oxidoreductases, new analytical methods
      were developed which are useful for the detection and during monitoring of
      phenylketonuria (PKU) or maple syrup urine disease (MSUD).

PMID- 9002208
TI  - Enzymes and antibodies in organic media: analytical applications.
AB  - This chapter outlines the influence of organic solvents on antibodies, enzymes,
      and their reactions, the different kinds of enzyme-solvent systems and the
      various advantages of organic solvents compared with water, with respect to
      analytical purposes. Examples for electrochemical, optical and thermometric
      assays in organic solvents are given. The potential of organic solvents for the
      modification of immunoassays is exemplified, opening up new applications.

PMID- 9002207
TI  - Phenol-oxidizing enzymes: mechanisms and applications in biosensors.
AB  - Phenolic compounds are widely distributed in nature. Enzymes which catalyze their
      oxidation are monophenol monooxygenases, such as tyrosinases and laccases, and
      peroxidases. Their metabolic role includes the decomposition of natural complex
      aromatic polymers as well as polymerization of the oxidation products and the
      degradation of xenobiotics. Their catalytic properties and broad availability
      gained impact on the development of biosenors for both environmentally important
      pollutants and clinically relevant metabolites. Mechanisms for the phenol
      oxidizine enzymes tyrosinases, laccases, and peroxidases are reviewed and some
      examples for their use in the construction of phenol selective biosenors are
      given.

PMID- 9002209
TI  - Nucleic acid based sensors.
AB  - Nucleic acids may be analyte or molecular recognition elements in biosensors.
      Both aspects merge in the genosensor approach, where detection of special
      sequences is facilitated by hybridization of a target nucleic acid to a
      complementary immobilized template. All three roles of nucleic acids in
      biosensors are discussed and the state of sensor development reviewed. With the
      invention of evolutionary synthesis strategies applied to nucleic acids new types
      of biomolecular receptors are accessible. The impact of aptamers and ribozymes on
      biosensor development is discussed.

PMID- 9002210
TI  - Receptor based chemical sensing.
AB  - This mini-review describes our recent approach of mimicking transmembrane and
      intracellular signalings displayed by various receptors in biomembranes for the
      development of new sensing membranes. Several important modes of receptor
      signaling have been utilized exploiting bio and synthetic receptors; (i) Ca2+
      signaling by calmodulin, (ii) active transport of target and relevant compounds
      displayed by Na+/D-glucose cotransporter and Na+,K(+)-ATPase, (iii) membrane
      permeability changes induced by glutamate receptor ion channel proteins and (iv)
      membrane potential changes induced by synthetic receptors. The newly designed
      sensing systems are demonstrated and discussed in terms of their novel mode of
      signal transduction, sensitivity and selectivity.

PMID- 9002211
TI  - Genetically modified Escherichia coli for colorimetric detection of inorganic and
      organic Hg compounds.
AB  - A sensitive colorimetric bacterial system was developed for the detection of
      Hg(II) and organomercury compounds. The bioactive species, a recombinant
      Escherichia coli, produces proportionally elevated levels of the enzyme beta
      galactosidase with increasing amounts of Hg. This is due to a reporter plasmid
      which carriers a Hg(II)-inducible promoter (mer promoter) from the Hg resistance
      transposon Tn501 regulating the transcription of a promoterless lacZ gene.
      Additionally, a pMB1 origin of replication without the natural RNA polymerase
      start site is fused downstream of the mer promoter leading to a Hg(II)-inducible
      plasmid replication, which results in an improved signal-to-noise ratio. To
      enhance the sensitivity of this cellular biosensor, the transport proteins for
      Hg(II) uptake are constitutively produced by a helper plasmid. To enable the
      detection of organically bound Hg, the Streptomyces lividans organomercurical
      lyase, an enzyme which catalyses the cleavage of C-Hg-bonds of organomercurial
      compounds, is also provided by the helper plasmid. Hg(II) and phenylmercuric
      acetate (PMA) concentrations as low as 5 x 10(-10) M (0.1 ppb) may be detected
      within a few minutes.

PMID- 9002212
TI  - Studies on pyroelectric response of polymers modified with azobenzene moieties.
AB  - In this review we present investigations on new materials and arrangements for
      new pyroelectric sensor devices. We applied pyroelectrical measurements on thin
      films based upon poly(vinyl alcohol)s and poly(siloxane)s with azobenzene side
      chains and discuss the relaxation behaviour and stability of poled pyroelectric
      polymers. Results on special poly(vinyl alcohol)s with side chains consisting of
      azobenzene unit and aliphatic head group are comparable with those achieved by
      poly(vinylidene fluoride) (PVDF). The new radiation-sensitive material seemed to
      be suitable as a detector system for the in situ determination of glucose in
      blood. Further developments of a complex detector system are now under
      investigation.

PMID- 9002214
TI  - Coupling of enzyme reactions to the charge transfer at the interface of two
      immiscible solvents.
AB  - Electrochemical principle of ion-selective electrodes (ISEs) based on the ion
      transfer reactions across a polarizable organic or oil/aqueous or water interface
      is described; the amperometric ISE and the potentiometric ISE are addressed.
      Electrochemical sensors and biosensors based on amperometric ISEs are discussed
      in some details. Amperometric sensors for monitoring ammonia (and other volatile
      amines) can be constructed on the basis of amperometric ammonium-ISE, where the
      pulse amperometric technique can successfully be employed. Urea and creatinine
      biosensors can also be fabricated by immobilizing urease or creatinine deiminase,
      respectively, on the surface of the amperometric ammonia sensor. Some favored
      characteristics of amperometric ISE-based sensors and biosensors are discussed
      with reference to the sensors and biosensors described.

PMID- 9002213
TI  - Forster energy transfer in ultrathin polymer layers as a basis for biosensors.
AB  - A method of detecting the binding of analyte molecules to biospecific receptors,
      like antibodies, is described. Forster energy transfer is used in connection with
      monomolecular organic films. The films are built up from pre-polymerized
      materials using the Langmuir-Blodgett or self-assembly techniques. Fluorescent
      dyes (as energy transfer donors) as well as reactive groups for covalent
      immobilization of protein receptors are integrated into the polymers. Several
      different methods for immobilizing biomolecules are described, including the use
      of protein A and the biotin/streptavidin couple. The studies suggest that the
      combination of Forster transfer and ultrathin organic films can be used for the
      construction of biosensors working either by displacement or by competitive
      assays. The mannose/concanavalin A, digoxin/antibody, and mouse immunoglobulin
      G/antibody systems are investigated. Further, a simplified meter optimized for
      measuring the fluorescence ratio at two wavelengths is described.

PMID- 9002215
TI  - Electron transfer via redox hydrogels between electrodes and enzymes.
AB  - The molecular "wiring" of redox enzymes provides the basis for amperometric
      enzyme and affinity sensors. The key features of the useful redox polymers are
      hydrophilicity and flexibility.

PMID- 9002216
TI  - Microbiosensors using electrodes made in Si-technology.
AB  - The combination of electrochemical transducers made in silicon technology with
      chemical and biochemical components has been used to manufacture miniaturized
      sensor structures. Three different types of sensors have been developed and
      optimized for practical use; (i) an ion-selective sensor, (ii) a glucose enzyme
      sensor, (iii) a redox-amplifying sensor for immunosensing. The immunodetection
      based on the redox recycling of mediator molecules is shown for low and high
      molecular weight analytes. The sensors have been integrated with miniaturized
      fluidic components and combined with sensor-related electronics and a common
      microcontroller.

PMID- 9002217
TI  - Angiogenesis and angiogenesis inhibition: an overview.

PMID- 9002218
TI  - Role of the macrophage in angiogenesis-dependent diseases.

PMID- 9002219
TI  - Angiogenesis in human gliomas: prognostic and therapeutic implications.

PMID- 9002220
TI  - Regulation of angiogenesis in malignant gliomas.
AB  - Gliomas are highly resistant to conventional therapeutic measures, requiring the
      development of novel treatments. Since gliomas are particularly vascular tumors,
      one approach involves treatments directed at inhibiting angiogenic mechanisms.
      Although multiple factors contribute to the ultimate vascularization of any
      tumor, some are especially relevant to gliomas. Early experimental work directed
      at inhibiting angiogenic pathways has shown promise toward achieving control of
      tumor growth. This article focuses on the evidence that angiogenesis and related
      vascular cell responses play important roles in glioma biology, and reviews those
      biochemical pathways known through experimentation to be involved in the vascular
      response to gliomas. Finally, contemporary vessel-targeted approaches that have
      been used to inhibit glioma growth are discussed.

PMID- 9002221
TI  - Lymphangiogenesis: mechanisms, significance and clinical implications.

PMID- 9002223
TI  - Angiostatin: an endogenous inhibitor of angiogenesis and of tumor growth.
AB  - Angiostatin, an internal fragment of plasminogen, is a potent inhibitor of
      angiogenesis, which selectively inhibits endothelial cell proliferation. When
      given systemically, angiostatin potently inhibits tumor growth and can maintain
      metastatic and primary tumors in a dormant state defined by a balance of
      proliferation and apoptosis of the tumor cells. We identified angiostatin while
      studying the phenomenon of inhibition of tumor growth by tumor mass and have
      elucidated one mechanism for this phenomenon. In our animal model, a primary
      tumor almost completely suppresses the growth of its remote metastases. However,
      after tumor removal, the previously dormant metastases neovascularize and grow.
      When the primary tumor is present, metastatic growth is suppressed by a
      circulating angiogenesis inhibitor. Serum and urine from tumor-bearing mice, but
      not from controls, specifically inhibit endothelial cell proliferation. The
      activity copurifies with a 38 kD plasminogen fragment which we have sequenced and
      named angiostatin. Human angiostatin, obtained from a limited proteolytic digest
      of human plasminogen, has similar activities. Systemic administration of
      angiostatin, but not intact plasminogen, potently blocks neovascularization and
      growth of metastases and primary tumors. We here show that the inhibition of
      metastases by a primary mouse tumor is mediated, at least in part, by the
      angiogenesis inhibitor angiostatin.

PMID- 9002222
TI  - Vascular permeability factor/vascular endothelial growth factor: a
      multifunctional angiogenic cytokine.
AB  - VPF/VEGF is a multifunctional cytokine that contributes to angiogenesis by both
      direct and indirect mechanisms. On the one hand, VPF/VEGF stimulates the
      endothelial cells lining nearby microvessels to proliferate, to migrate and to
      alter their pattern of gene expression. On the other hand, VPF/VEGF renders these
      same microvascular endothelial cells hyperpermeable so that they spill plasma
      proteins into the extravascular space, leading to profound alterations in the
      extracellular matrix that favor angiogenesis. These same principles apply in
      tumors, in several examples of non-neoplastic pathology, and in physiological
      processes that involve angiogenesis and new stroma generation. In all of these
      examples, microvascular hyperpermeability and the introduction of a provisional,
      plasma-derived matrix precede and accompany the onset of endothelial cell
      division and new blood vessel formation. It would seem, therefore, that tumors
      have made use of fundamental pathways that developed in multicellular organisms
      for purposes of tissue defense, renewal and repair. VPF/VEGF, therefore, has
      taught us something new about angiogenesis; namely, that vascular
      hyperpermeability and consequent plasma protein extravasation are important-
      perhaps essential--elements in its generation. However, this finding raises a
      paradox. While VPF/VEGF induces vascular hyperpermeability, other potent
      angiogenic factors apparently do not, at least in sub-toxic concentrations that
      are more than sufficient to induce angiogenesis (Connolly et al., 1989a).
      Nonetheless, wherever angiogenesis has been studied, the newly generated vessels
      have been found to be hyperpermeable. How, therefore, do angiogenic factors other
      than VPF/VEGF lead to the formation of new and leaky blood vessels? We do not as
      yet have a complete answer to this question. One possibility is that at least
      some angiogenic factors mediate their effect by inducing or stimulating VPF/VEGF
      expression. In fact, there are already clear example of this. A number of
      putative angiogenic factors including small molecules (e.g. prostaglandins,
      adenosine) as well as many cytokines (e.g. TGF-alpha, bFGF, TGF-beta, TNF-alpha,
      KGF, PDGF) have all been shown to upregulate VPF/VEGF expression. Further studies
      that elucidate the crosstalk among various angiogenic factors are likely to
      contribute significantly to a better understanding of the mechanisms by which new
      blood vessels are formed in health and in disease.

PMID- 9002224
TI  - Thrombospondin as a regulator of angiogenesis.

PMID- 9002225
TI  - Regulation of capillary formation by laminin and other components of the
      extracellular matrix.
AB  - The process of angiogenesis (vessel formation) and the resulting stabilization of
      the mature vessel are complex events that are highly regulated and require
      signals from both serum and the extracellular matrix. Endothelial cells rest on a
      specialized thin extracellular matrix known as the basement membrane. Endothelial
      cells lining normal blood vessels are usually quiescent. When a proper stimulus
      is present, angiogenesis beings when endothelial cells degrade their basement
      membrane and invade the surrounding extravascular matrix. Formation of new
      vessels involves the migration and proliferation of cells. To assist the cells in
      their migration, the extravascular matrix provides an environment rich in stromal
      collagen fibers, fibrin, hyaluoronic acid, vitronectin and fibronectin. Once the
      endothelial cells assemble to form a new vessel, the cells secrete a basement
      membrane that helps to stabilize and maintain the vessel wall. The basement
      membrane adheres tightly to cells comprising the vessel wall, provides inductive
      signals, and plays a important role in the homeostasis of new vessels. We have
      demonstrated that two major components of the basement membrane, laminin and
      collagen IV, possess endothelial cell binding sites which regulate vessel
      stability. In this chapter, we will define the role of these molecules in
      endothelial cell behavior.

PMID- 9002226
TI  - Hypoxia and angiogenesis in experimental tumor models: therapeutic implications.

PMID- 9002227
TI  - The role of vascular cell integrins alpha v beta 3 and alpha v beta 5 in
      angiogenesis.

PMID- 9002228
TI  - Role of fibrin and plasminogen activators in repair-associated angiogenesis: in
      vitro studies with human endothelial cells.
AB  - Angiogenesis, the formation of new blood vessels from existing ones, plays a
      central role in development and in a number of pathological conditions. Tissue
      repair-associated angiogenesis usually involves cell invasion into a fibrin
      structure and the presence of inflammatory cells. In this chapter the role of
      plasminogen activators in the dissolution of fibrin and the invasion of
      endothelial cells into a fibrin matrix is described. Tissue-type plasminogen
      activator is stored in endothelial cells and can be released acutely into the
      vessel lumen upon stimulation of the endothelium to activate fibrinolysis and to
      prevent fibrin deposition. At the basolateral side of the cell, urokinase-type
      plasminogen activator (uPA) bound to a specific cellular receptor is involved in
      the proteolytic modulation of matrix proteins and cell-matrix interaction. The
      cytokine tumor necrosis factor-alpha (TNF-alpha) cooperates with the angiogenic
      factors basic fibroblast growth factor (bFGF) and vascular endothelial growth
      factor (VEGF) in inducing human microvascular endothelial cells in vitro to
      invade a three dimensional fibrin matrix and to form capillary-like tubular
      structures. The formation of these capillary-like tubules requires cell-bound uPA
      activity.

PMID- 9002229
TI  - Tumor angiogenesis: functional similarities with tumor invasion.
AB  - In this review the functional relationship between tumor cell invasion and tumor
      induced angiogenesis is discussed. Emphasis is placed on the similarities of the
      invasive phenotype in both processes and the common themes of alpha v beta 3
      expression and gelatinase A activity.

PMID- 9002230
TI  - Control of angiogenesis by the pericyte: molecular mechanisms and significance.
AB  - The microvasculature consists of endothelial cells (EC) with albuminally located
      pericytes. A number of clinical and experimental observations suggest that
      pericytes contribute to the regulation of microvascular growth and function. EC
      and pericytes appear to have a variety of means whereby they may influence one
      another, including soluble growth factors, gap junctions and adhesion molecules,
      to name a few. Co-culture systems have provided a good deal of evidence to
      support the concept that these two cells interact and that these communications
      are central to vessel assembly, growth control and normal function.

PMID- 9002231
TI  - Angiogenesis as a biologic and prognostic indicator in human breast carcinoma.
AB  - In this review we describe angiogenesis pathways involved in the development of
      breast carcinoma. Different assessment techniques for angiogenesis and their
      optimisation are discussed. Angiogenesis is an important factor for prognosis and
      will be increasingly important in therapeutic decisions.

PMID- 9002232
TI  - Fibroblast growth factors as angiogenesis factors: new insights into their
      mechanism of action.

PMID- 9002233
TI  - Regulation of angiogenesis by scatter factor.
AB  - Scatter factor (SF, hepatocyte growth factor) is a cytokine that stimulates
      motility, proliferation, and morphogenesis of epithelia. These responses are
      transduced through a tyrosine kinase receptor that is encoded by a proto-oncogene
      (c-met). SF is a potent angiogenic molecule, and its angiogenic activity is
      mediated, in part, through direct actions on endothelial cells. These include
      stimulation of cell motility, proliferation, protease production, invasion, and
      organization into capillary-like tubes. SF also stimulates the proliferation of
      smooth muscle cells and pericytes, cell types that also participate in the
      formation of capillaries and other microvessels. SF is chronically overexpressed
      in tumors, and it is postulated SF may function as a tumor angiogenesis factor.
      SF production in tumors may be due, in part, to an abnormal tumor: stroma
      interaction in which tumor cells secrete soluble proteins (SF-inducing factors)
      that stimulate stromal cell SF production and in part to autocrine production by
      the tumor cells themselves. Recent studies suggest a linkage between tumor
      suppressors (anti-oncogenes) and inhibition of angiogenesis. We hypothesize that
      tumor suppressor gene mutations may contribute to activation of an SF-->c-met
      signalling pathway, leading to an invasive and angiogenic tumor phenotype.
      Modulation of this pathway may provide clinically useful methods of enhancing or
      inhibiting angiogenesis.

PMID- 9002234
TI  - Vascular endothelial growth factor: basic biology and clinical implications.

PMID- 9002235
TI  - Tropomyosin isoforms in nonmuscle cells.
AB  - Vertebrate nonmuscle cells, such as human and rat fibroblasts, express multiple
      isoforms of tropomyosin, which are generated from four different genes and a
      combination of alternative promoter activities and alternative splicing. The
      amino acid variability among these isoforms is primarily restricted to three
      alternatively spliced exon regions; an amino-terminal region, an internal exon,
      and a carboxyl-terminal exon. Recent evidence reveals that these variable exon
      regions encode amino acid sequences that may dictate isoform-specific functions.
      The differential expression of tropomyosin isoforms found in cell transformation
      and cell differentiation, as well as the differential localization of tropomyosin
      isoforms in some types of culture cells and developing neurons suggest a
      differential isoform function in vivo. Tropomyosin in striated muscle works
      together with the troponin complex to regulate muscle contraction in a Ca(2+)
      dependent fashion. Both in vitro and in vivo evidence suggest that multiple
      isoforms of tropomyosin in nonmuscle cells may be required for regulating actin
      filament stability, intracellular granule movement, cell shape determination, and
      cytokinesis. Tropomyosin-binding proteins such as caldesmon, tropomodulin, and
      other unidentified proteins may be required for some of these functions. Strong
      evidence for the distinct functions carried out by different tropomyosin isoforms
      has been generated from genetic analysis of yeast and Drosophila tropomyosin
      mutants.

PMID- 9002236
TI  - Pro-opiomelanocortin-derived peptides, cytokines, and nitric oxide in immune
      responses and stress: an evolutionary approach.
AB  - In vertebrates, including man, the study of stress has contributed substantially
      to unravelling the complex relationship between immune-neuroendocrine
      interactions and the systems involved. On the basis of data on the presence and
      distribution of the main actors (POMC products, cytokines, biogenic amines, and
      steroid hormones) in different species and taxa from invertebrates to
      vertebrates, we argue that these responses have been deeply connected and
      interrelated since the beginning of life. Moreover, the study of nitric oxide
      suggests that the inflammatory reaction is located precisely between the immune
      and stress responses, sharing the same fundamental evolutionary roots. The major
      argument in favor of this hypothesis is that the immune, stress, and inflammation
      responses appear to be mediated by a common pool of molecules that have been
      conserved throughout evolution and that from a network of adaptive mechanisms.
      One cell type, the macrophage, appears to emerge as that most capable of
      supporting this network critical for survival; it was probably a major target of
      selective pressure. All these data fit the unitarian hypothesis we propose, by
      which evolution favors what has been conserved, rather than what has changed, as
      far as both molecules and functions are concerned.

PMID- 9002237
TI  - Mammalian skeletal muscle fiber type transitions.
AB  - Mammalian skeletal muscle is an extremely heterogeneous tissue, composed of a
      large variety of fiber types. These fibers, however, are not fixed units but
      represent highly versatile entities capable of responding to altered functional
      demands and a variety of signals by changing their phenotypic profiles. This
      adaptive responsiveness is the basis of fiber type transitions. The fiber
      population of a given muscle is in a dynamic state, constantly adjusting to the
      current conditions. The full range of adaptive ability spans fast to slow
      characteristics. However, it is now clear that fiber type transitions do not
      proceed in immediate jumps from one extreme to the other, but occur in a graded
      and orderly sequential manner. At the molecular level, the best examples of these
      stepwise transitions are myofibrillar protein isoform exchanges. For the myosin
      heavy chain, this entails a sequence going from the fastest (MHCIIb) to the
      slowest (MHCI) isoform, and vice-versa. Depending on the basal protein isoform
      profile and hence the position within the fast-slow spectrum, the adaptive ranges
      of different fibers vary. A simple transition scheme has emerged from the
      multitude of data collected on fiber type conversions under a variety of
      conditions.

PMID- 9002238
TI  - Acute phase proteins and transformed cells.
AB  - Acute phase proteins (APP) are plasma proteins whose concentration and
      glycosylation alters in response to tissue injury, inflammation, or tumor growth.
      Significant interspecies and sex differences in APP response exist. APP are
      produced mainly by hepatocytes, and their synthesis and glycosylation are
      controlled by a network consisting of cytokines, their soluble receptors, and
      glucocorticoids. The major cytokines involved in these processes belong to a
      group of interleukin-6-type cytokines that act through the hematopoietin receptor
      complex on hepatocytes and JAK-STAT signal transduction pathway. Transformed
      cells (hepatoma) display significant differences in synthesis of APP, cytokine
      responsiveness, expression of cytokine-receptor subunits and signal-transduction
      machinery. The most striking variability relates to the glycosylation alterations
      induced by cytokines. However, transformed cells (hepatoma) form a basic model
      for studying and understanding mechanisms controlling the synthesis and
      glycosylation of APP. Furthermore, APP may be secreted by transformed (tumor)
      cells of various origins and may display a growth factor-like function in certain
      cancer types.

PMID- 9002239
TI  - A mathematical model for drug administration by using the phagocytosis of red
      blood cells.
AB  - A mathematical model for the delivery of drug directly to the macrophages by
      using the phagocytosis of senescent red blood cells is proposed. The model is
      based on the following assumption: At time t = 0 a preassigned red blood cell
      population n(0,a) = phi (a), a > 0, loaded by the drug, is injected in the blood
      circulation. Among the cells of that population only those with an age a > or = a
      (a = 120 days) will be phagocytosed by macrophages. Of course, the lifetime of
      the drug must be higher than a. Within the red blood cells it cannot be
      metabolized, neither can it diffuse through their membranes. The emphasis of the
      paper is on the mathematical properties and on the formulation of the control
      problem.

PMID- 9002240
TI  - Multiparametric bifurcations for a model in epidemiology.
AB  - In the present paper we make a bifurcation analysis of an SIRS epidemiological
      model depending on all parameters. In particular we are interested in codimension
      2 bifurcations.

PMID- 9002241
TI  - Strategy for control of complex low-dimensional dynamics in cardiac tissue.
AB  - Heart rate-dependent alterations in the duration of the electrically active state
      of cardiac cells, the action potential, are an important determinant of lethal
      heart rhythm disorders. The relationship between action potential duration and
      heart rate can be modelled as a nonlinear one-dimensional map. Iteration of the
      map over a range of physiologically relevant heart rates produces complex changes
      in action potential duration, including period doubling bifurcations, chaos and
      period doubling reversals. We present a computer algorithm that ensures, over the
      same range of heart rates, uniform state variable values (action potential
      durations) by application of small perturbing stimuli at appropriate intervals.
      The algorithm succeeds, even though the only parameter in the system (the heart
      rate) is immutable. Control of the dynamics is achieved by exploiting the
      inexcitability of the cardiac cells immediately after stimulation. This algorithm
      may have applications for the prevention of cardiac rhythm disturbances.

PMID- 9002243
TI  - Parabolic bursting revisited.
AB  - Many excitable membrane systems display bursting oscillations, in which the
      membrane potential switches periodically between an active phase of rapid spiking
      and a silent phase of slow, quasi steady-state behavior. A burster is called
      parabolic when the spike frequency is lower both at the beginning and end of the
      active phase. We show that classes of voltage-gated conductance equations can be
      reduced to the mathematical mechanism previously analyzed by Ermentrout and
      Kopell in [7]. The reduction uses a series of coordinate changes and shows that
      the mechanism in [7] applies more generally than previously believed. The key
      hypothesis for the more general theory is that a certain slow periodic orbit must
      stay close to a curve of degenerate homoclinic points for the fast system, at
      least during the active phase. We do not require that the slow system have a
      periodic orbit when the voltage is held constant.

PMID- 9002242
TI  - Modeling tendon morphogenesis in vivo based on cell density signaling in cell
      culture.
AB  - A mathematical model of tendon morphogenesis is presented that is consistent with
      the dramatic transitions seen in this tissue as it progresses from rapid growth
      early in development to no growth in the adult. To accomplish this change, the
      embryonic chick tendon is hypercellular with each cell dedicating half of its
      protein production to procollagen but over time, as growth subsides, the tissue
      gradually becomes hypocellular with each cell producing only about 1%
      procollagen. Making this transition from the embryonic to the adult state,
      forming a roughly cylindrical tissue composed of approximately 90% collagen, and
      linking the correct muscle to the right bone, is a complex task. The proposed
      solution requires only two factors: an activator of growth and an inhibitor
      complex, composed of the activator and another molecule that modifies the
      activity of the activator. From a diverse set of cell culture observations, these
      two factors were deduced as the primary components of the mechanism that allows
      cells to signal their presence to their neighbors. Since cell density signaling
      is the principal regulator of both collagen synthesis and cell proliferation, its
      components should play the key role in tendon development. A mathematical model
      based on the changes in the concentrations of these factors with cell density
      correlates well with the transitions observed in vivo. Furthermore, the model
      predicts that in the maturing chicken there should be a high cell density region
      at the muscle tendon interface. Experimental observations of frozen sections of
      tendon from a 4 month old chicken confirm this prediction.

PMID- 9002244
TI  - Tumour photosensitizers: approaches to enhance the selectivity and efficiency of
      photodynamic therapy.
AB  - While Photofrin, the photosensitizer currently in clinical use for photodynamic
      therapy (PDT) of tumours, has been shown to be both efficacious and safe in the
      treatment of a variety of human cancers, its chemical heterogeneity and low
      absorbance in the phototherapeutically useful wavelength range (600-850 nm) make
      the development of new photosensitizers with improved characteristics desirable.
      A suitable manipulation of the molecular structure of porphyrins offers several
      interesting possibilities for controlling the optical and photophysical
      properties of the photosensitizer, as well as its biodistribution between tumour
      and peritumoural tissues or at the subtissular and subcellular level. The
      achievement of these goals may also be facilitated by the association of the
      photosensitizer with selected delivery systems, opening the way to a qualitative
      and quantitative improvement of PDT.

PMID- 9002245
TI  - Natural products derived from plants as potential drugs for the photodynamic
      destruction of tumor cells.
AB  - Chlorophyll and some of its synthetically produced derivatives are important
      sensitizers in photodynamic cancer therapy. Other natural products from plants
      with light dependent activity include quinones like hypericin and fagopyrin.
      These compounds have extended pi-electron systems which upon photoexcitation with
      visible light are responsible for singlet oxygen production. Other plant
      constituents which show UV light induced photosensitizing activity are
      furanocumarins like psoralen and angelicin, aflatoxins and alkaloids, as well as
      thiophene derivatives, terthienyl and several polyacetylenes. The photodynamic
      properties of a chelidonium alkaloid derivative and data for its potential
      clinical applicability are given.

PMID- 9002246
TI  - Wavelength-dependent photoresponse of biological and aqueous model systems using
      the photodynamic plant pigment hypericin.
AB  - Photodynamic eradication of tumour cells in vivo depends on the presence of a
      photosensitizer, light delivery to the cells, and an oxygen supply. Hypericin, a
      polycyclic quinone with absorption maxima in the ultraviolet and visible ranges,
      was prepared for clinical use as a photosensitizer. Due to antitumoral and
      antineoplastic activities as well as the generation of singlet oxygen after
      photoexcitation, hypericin was applied in clinical oncology and photodynamic
      therapy. Hypericin was administered subcutaneously (20 micrograms hypericin in
      200 microliters Nacl/pyridine solution) into the ante brachium (forearm) of two
      volunteers. After the diffusion and equilibration of 120 min phototesting was
      carried out using outdoor light exposure, halogen lamp, laser 514 nm (argon),
      laser 632 nm (argon dye) and laser 670 nm (diode laser), from 60 to 120 J cm-2.
      Positive phototests to outdoor light exposure, halogen lamp and laser 514 nm were
      characterized by rubescence, oozing, vesiculation and darting pain. Phototests
      with laser 632 nm and 670 nm showed no effects after irradiation. When hypericin
      was administered topically on skin, erythema and flaring could not be induced by
      any irradiation. These results suggest that hypericin is a potent photosensitizer
      only within the UV and green light ranges. This characteristic photoresponse
      could also be obtained in guinea pig papillary muscle (GPPM) bioassay, which may
      be established as a model for photosensitizer testing. Irradiation of hypericin
      incubated GPPM with 514 nm (20 J cm-2) led to a decrease of the contractile force
      of about 31%. However, excitation with 632 nm and 670 nm did not cause inotropic
      effects on GPPM. In addition, hypericin and Photosan 3 were shown to be capable
      of sensitizing the photo-oxidation of sodium linoleate. This assay should be
      established for testing interactions between photosensitizers and light sources
      in vitro.

PMID- 9002247
TI  - Hypericin in phototherapy.
AB  - We describe the first local use of hypericin as photosensitizer for photodynamic
      therapy in a patient with recurrent malignant mesothelioma. Hypericin is a
      polycyclic quinone, which has been shown to possess in vivo and in vitro
      antiretroviral and photosensitizing activity; moreover, it is used in depressive
      disorders. The semiquinone radical, singlet oxygen, and superoxide anion radical
      are reported to be the toxic agents in hypericin phototherapy. Our first
      experience with locally applied hypericin in a superficial tumor-plate was
      performed 8 weeks after the systemic administration of hematoporphyrin
      derivatives. For tumor light illumination we used an argon pumped dye laser tuned
      to 632 nm. Owing to satisfactory results, we repeated the same therapy 4 weeks
      later- and no therapeutic effect was noted. Following this, we proved the
      interstitial application of HPD and the combination of interstitial HDP and
      superficially applied hypericin. The subsequent light illumination 6 hours later
      had no efficacy in the HDP-photosensitized area but there was tumor destruction
      in the field with both administered photosensitizers. Our first experience
      suggests a potentiation of two photosensitizers: hematoporphyrin derivatives and
      hypericin.

PMID- 9002248
TI  - In-vitro investigation of ALA-induced protoporphyrin IX.
AB  - Protoporphyrin IX (PpIX) induced endogenously by delta-aminolevulinic acid (ALA),
      can be used to destroy photodynamically tumor cells. The influence of several
      parameters on the PpIX formation of human skin fibroblasts was investigated by
      fluorescence spectrophotometry. The PpIX formation increases (1) with the pH
      value of ALA (2) with the ALA incubation time in a moderate sigmoidal manner, and
      (3) with the ALA concentration up to 700 micrograms ml-1. Other parameters, such
      as cell washing procedures, have no influence on the PpIX production. ALA has to
      be applied in a concentration 30 times higher than external protoporphyrin IX and
      Photosan 3 in order to produce the same cytotoxic damage. Protoporphyrin
      bleaching and photoproduct generation at 646 nm was observed. Additional
      information about intracellular PpIX formation kinetics and its topographically
      correlation to cell structures was gained by a CCD camera mounted on a
      fluorescence microscope. A few minutes after the onset of incubation with ALA,
      PpIX generation is observed in the mitochondria, followed by relocalization in
      the cytoplasm and the nuclear membrane.

PMID- 9002249
TI  - Dynamic fluorescence changes during photodynamic therapy in vivo and in vitro of
      hydrophilic A1(III) phthalocyanine tetrasulphonate and lipophilic Zn(II)
      phthalocyanine administered in liposomes.
AB  - The fluorescence emission of hydrophilic tetrasulphonated aluminium
      phthalocyanine (AlPcS4) and hydrophobic zinc phthalocyanine (ZnPc), bound to the
      membrane of liposomes, was investigated in vivo in an appropriate tumour model of
      the rat bladder and in RR 1022 epithelial cells of the rat. The sensitizers were
      administered systemically to the rats and photodynamic therapy (PDT) was
      performed 24 h later. During PDT treatment, the fluorescence was measured every
      30 s. The fluorescence was excited with 633 nm light from an HeNe laser and the
      fluorescence spectra were detected with an optical multichannel analyser system.
      PDT was performed for both sensitizers using 672 nm light from an Ar+ dye laser.
      The fluorescence changes during PDT were significantly different for the two
      phthalocyanines. For AlPcS4, an initial fluorescence intensity increase, followed
      by subsequent photobleaching, was observed. In contrast, ZnPc fluorescence showed
      an exponential decrease and no increase at the start of treatment. Tumour
      necrosis 24 h after PDT was significant only for ZnPc. RR 1022 cells incubated
      for 24 h with AlPcS4 revealed a granular fluorescence pattern, whereas ZnPc was
      localized diffusely in the cytoplasm of the cells. In agreement with the in vivo
      measurements, subcellular relocalization and a fluorescence intensity increase
      were detected exclusively in the case of AlPcS4. Morphological changes at this
      time were significant only for ZnPc. The subcellular localization and
      fluorescence kinetics were obtained using a confocal laser scanning microscope.

PMID- 9002250
TI  - Determination of Photosan III in human plasma.
AB  - In order to develop an accurate and quick method for the determination of
      Photosan III in human plasma, we used statistically planned experiments with an
      aim to identify the factors that can influence the analysis. Through a series of
      20 experiments based on acid extraction of the porphyrin from the plasma and
      subsequent fluorescence analysis a calibration was obtained between 0 and 3.3 x
      10(-5) M. The deviation of the parameters around the regression line is 3.02%,
      the coefficient of variation 3.55%.

PMID- 9002251
TI  - Measurements by fluorescence microscopy of the time-dependent distribution of
      meso-tetra-hydroxyphenylchlorin in healthy tissues and chemically induced "early"
      squamous cell carcinoma of the Syrian hamster cheek pouch.
AB  - The influence of the time interval between dye administration and detection by
      fluorescence microscopy was assessed in "early" squamous cell carcinomas of the
      cheek pouch mucosa and different healthy tissues of the Syrian hamster. Following
      intracardiac injection of 0.15 mg (kg bodyweight)-1 of meso-tetra
      hydroxyphenylchlorin (m-THPC), groups of three animals were sacrificed at
      different time intervals up to 30 days. A group of three non-injected animals was
      used to detect the endogene fluorescence of the corresponding normal tissues for
      autofluorescence subtraction. The following excised organs (oesophagus, trachea,
      liver, spleen, kidney, skin, striated muscle, healthy and tumoral cheek pouch
      mucosae) were fast frozen in liquid nitrogen and stored at -70 degrees C for
      fluorescence microscopy. The results show significant differences in the
      detectable m-THPC levels in different tissue layers (for instance, the epithelia
      and muscle of the oesophagus, trachea and cheek pouch) at different time
      intervals. These data indicate that pharmacokinetic studies may be useful for
      selecting the optimal time for the photodetection and phototherapy of cancer.

PMID- 9002252
TI  - Systems for light application and dosimetry in photodynamic therapy.
AB  - Successful photodynamic therapy requires homogeneous irradiation and light
      detection for dosimetry. Light delivery devices and detectors for treatment of
      spherical and cylindrical hollow organs have been developed. For photodynamic
      therapy of multifocal superficial bladder tumours a catheter with an isotropic
      emitter is centred by a balloon. Light which is backscattered from the tissue
      surface is used for on-line dosimetry. The irradiation and dosimetry concept has
      been proven by computer simulations for a non-spherical bladder shape. Larynx,
      bronchi, oesophagus and cervix have been irradiated by devices adapted to the
      shape of the organ. The light distribution is homogenized by multiple
      backscattering from a nearly white layer in contact with tissue, a promising
      method also for hollow organs with irregular geometry. The homogeneity of the
      light distribution as well as the dosimetry have been improved by the devices to
      be presented.

PMID- 9002253
TI  - Photodynamic therapy in neurosurgery: a review.
AB  - Photodynamic therapy (PDT) has been investigated extensively, both experimentally
      and clinically, as an adjunctive treatment in the neuro-oncological field. It is
      based on the more selective accumulation of a photosensitizer in malignant than
      normal tissue with low systemic toxicity. Subsequent light activation induces
      photo-oxidation, followed by selective tumour destruction via vascular and direct
      cellular mechanisms. Malignant brain tumours carry a lethal prognosis with a
      median survival of 15 months despite surgery, radiotherapy and chemotherapy. PDT
      is therefore a logical therapeutic concept for brain tumours infiltrating into
      normal brain. In this review, all the available data on patients treated with
      haematoporphyrin derivative-mediated PDT are critically analysed. Over 310
      patients have been reported in the literature suffering from primary or recurrent
      malignant brain tumours which were treated with PDT following tumour resection in
      open clinical phase I/II trials. This number includes 58 patients treated at our
      own institution. Variations in the treatment protocols make evaluation
      scientifically difficult; however, there is a clear trend of increased median
      survival after surgical resection and one single photodynamic treatment. PDT is
      generally well tolerated and side effects consist of moderate increased
      intracranial pressure and prolonged skin sensitivity to direct sunlight. The
      current available data indicate that PDT is a safe treatment, which is well
      tolerated by the patients and yields an improvement in survival of those with
      malignant brain tumours. Conclusive information can be expected from controlled
      clinical trials which are currently being designed. The results raise the hope
      that PDT will be a valuable addition to the armamentarium for the treatment of
      cerebral malignancies.

PMID- 9002254
TI  - Inhalation of 5-aminolevulinic acid: a new technique for fluorescence detection
      of early stage lung cancer.
AB  - Topical application of 5-aminolevulinic acid (5-ALA), with subsequent synthesis
      of protoporphyrin IX (PPIX), is a novel outstanding procedure for photodynamic
      treatment. So far, clinical experience has been reported with creams containing 5
      ALA for the therapy of skin cancer, oral application for the treatment of
      gastrointestinal disease and intravesical instillation of 5-ALA solutions for
      fluorescence detection of superficial bladder cancer. Inhalation of 5-ALA for the
      staining of bronchial malignancies is a preferred method in clinical pulmonology.
      Since no adverse reaction was observed in lung function in a canine following
      inhalation of 5-ALA in increasing concentrations, clinical applications were
      performed. Seven patients with positive or suspicious sputum cytology, but
      negative white light bronchoscopy, received 5-10 wt.% 5-ALA in NaCl solution by
      means of a medical nebulizer. No side effects were observed during and after 5
      ALA inhalation. After a period of 3 h, patients underwent fluorescence
      bronchoscopy using violet light for fluorescence excitation and an optical
      multichannel analyzer for fluorescence detection in situ. The results showed
      fluorescence spectra which could be related to PPIX induced by 5-ALA in the
      bronchial mucosa. The fluorescence intensity was sufficiently high for video
      imaging using a target integrating color CCD camera adapted to the flexible
      bronchoscope. Carcinoma in situ, as well as dysplasias, showed a clear positive
      fluorescence. A correlation of fluorescence contrast with histology on 30
      biopsies revealed a high sensitivity, but a specificity below 50%. Improvements
      in light and drug dosimetry will form the basis for further clinical trials.

PMID- 9002255
TI  - Photodynamic treatment for cancers of the head and neck.
AB  - A clinical study using photodynamic therapy (PDT) for the treatment of head and
      neck cancer was conducted between 1988 and 1994. 83 patients with Tis-2 tumors of
      the face, oropharynx and larynx were included into the study protocol. The study
      was designed in accordance with the GCP-guidelines as a prospective controlled
      protocol. At 48 h after an intravenous injection of 2 mg kgbw-1 Photosan-3 the
      laser illumination (630 nm) of the tumor and tumor-surrounding tissue was
      performed at 100 mW cm-2 and 100 J cm-2. A control biopsy from the former tumor
      area was taken 2 months after PDT to evaluate the histological response of the
      treated tumors. 51 out of 57 patients with basal cell carcinoma, 6 out of 7
      patients with squamaous cell carcinoma of the skin, 6 out of 7 patients with
      oropharynx carcinoma and 11 out of 12 patients with larynx carcinoma showed a
      complete histologically confirmed response to the tumor following a single course
      of PDT over a follow up time of 13-71 months.

PMID- 9002256
TI  - Photodynamic therapy within edematous brain tissue: considerations on sensitizer
      dose and time point of laser irradiation.
AB  - Photosensitizer is known to spread with vasogenic edema fluid arising from a
      cerebral lesion (Neurosurg 33:1075-1082, 1993), which may be essential for
      sensitizing malignant cells outside the main tumor mass. The present experiments
      seek to elucidate whether resultant necrosis of perifocal brain tissue after
      laser irradiation follows a corresponding time pattern and whether damage depends
      on the photosensitizer dose. Male Wistar rats were anaesthetized with
      chloralhydrate for venous cannulation, craniotomy and focal cold lesion in order
      to induce vasogenic edema. Simultaneously, Photofrin II (PF II) was administered
      at a dose of 5 mg kg-1. The animals were re-anaesthetized after either 4, 12 or
      24 h for the irradiation of lesion and perifocal tissue with 200 J cm-2 of laser
      light (630 nm). The brains of other animals were irradiated 4 h after cold lesion
      with 200 J cm-2 after receiving either 0, 2.5 or 5 mg kg-1 PF II (all groups: n =
      6). Resultant necrosis was assessed planimetrically in serial coronal
      cryosections of brains perfusion fixed 24 h after irradiation. Necrosis was
      significantly enhanced with irradiation 4 h after cold lesion and photosensitizer
      (avg. area +/- SD: 4.3 +/- 0.7 mm2) compared with lesion only (0.84 +/- 0.2 mm2).
      Maximal necrosis (6.3 +/- 1.6 mm2) occurred with irradiation 12 h after lesion,
      whereas necrosis was only slightly increased with irradiation at 24 h (2.8 +/-
      0.4 mm2). Furthermore, the area of necrosis was dependent on the sensitizer dose
      (0 mg kg-1: 0.7 +/- 0.3 mm2, 2.5 mg kg-1: 2.09 +/- 0.2 mm2, 5 mg kg-1: 4.3 +/-
      0.7 mm2; all differences p < 0.05). Therefore, to prevent unwanted side-effects
      such as necrosis of edematous but otherwise healthy, peritumoral tissue in the
      treatment of malignant cerebral tumors by PDT, tribute should be paid to the
      possibility of time and dose dependent sensitization of the perifocal tissue
      after i.v. administration of photosensitizer.

PMID- 9002257
TI  - Unusual adverse reaction in a patient sensitized with Photosan 3.
AB  - Serious side effects of photodynamic therapy (PDT) are rare (A.L. Abramson, M.J.
      Shikowitz, V.M. Mullooly, Clinical effects of photodynamic therapy on recurrent
      laryngeal papillomas, Arch. Otolaryngology Head Neck Surg., 118 (1992) 25-29;
      A.L. Abramson, M.J. Shikowitz, Clinical exacerbation of systemic lupus
      erythematosus after photodynamic therapy of laryngotracheal papillomatosis, Laser
      Surg. Med., 13 (1993) 677-679). The most frequent side effects of PDT are
      hypersensitive skin reactions, local edema, nausea, a metallic taste and liver
      toxicity (J. Feyh, E. Kastenbauer, Treatment of laryngeal papillomatosis with
      photodynamic laser therapy, Laryngorhinootologie, 71 (1992) 190-192; J. Feyh, R.
      Gutmann, A. Leunig, Die Photodynamische Therapie im Bereich der Hals-, Nasen-,
      Ohrenheilkunde Laryngorhinootologie, 72(6) (1993) 273-78; M.S. Kavuru, A.C.
      Mekta, Treatment of recurrent respiratory papillomatosis, N. Engl. J. Med., 326
      (1992) 204-205; B.L. Wenig, D.M. Kurtzmann, Photodynamic therapy in the treatment
      of squamous cell carcinomas of the head and neck, Arch. Otolaryngol Head Neck
      Surg., 116 (1990) 1267-1270). In this case a patient (aged 57 years) suffering
      from a recurrent larynx papillomatosis was treated with PDT. He was sensitized
      with Photosan 3 (DHE) 2.5 mg kg-1 body weight, 24 h prior to photoradiation. As a
      light source, an argon dye laser, operating at a wavelength of 630 nm was used,
      coupled with a cylindrical light applicator. After treatment the patient was
      admitted to an intensive care unit for 24 h. 3 h after photoradiation, general
      urticarial wheals arose, as well as tachycardia and a decrease in blood pressure
      followed by all the signs of serious anaphylaxis. 1.5 h after treatment with
      adrenaline and cortisone and stabilization of the cardiac and circulatory
      situation no more skin lesions were visible.

PMID- 9002258
TI  - Photodynamic therapy in selected cases at the ENT Clinic, Innsbruck: case
      reports.
AB  - Although photodynamic therapy (PDT) for the treatment of head and neck cancer has
      proved useful in other departments (J. Feyh, A. Goetz and W. Muller, Photodynamic
      therapy in head and neck surgery, J. Photochem. Photobiol. B: Biol., 7 (1990) 353
      358; V.G. Schweitzer, Photodynamic therapy for treatment of head and neck cancer,
      Arch. Otolaryngol. Head Neck Surg., 102 (1990) 225-232; B.L. Wenig, D.M.
      Kurtzmann and L.I. Grossweiner, Photodynamic therapy in the treatment of squamous
      cell carcinomas of the head and neck, Arch. Otolaryngol. Head Neck Surg., 116
      (1990) 1267-1270), it is not a standard therapy at the ENT Department of the
      University Clinic Innsbruck. PDT has only been applied in a few selected cases.
      Photosan 3 (dihaematoporphyrin either, DHE) was used as photosensitizer at a dose
      of 2.5 mg (kg body weight)-1 administered intravenously 24-48 h prior to
      photoirradiation. In one case, Photosan 3 was applied topically in a solution
      with 40% dimethylsulphoxide (DMSO). The light source was an argon dye laser with
      a wavelength of 630 nm and a power of 100 mW cm-2, coupled with a cylindrical or
      spherical applicator and a lens fibre tip. Patients suffering from cancer of the
      palatine arch, tonsil, nasal septum and glottis are reported. These selected
      cases had previous treatment (e.g. chemotherapy, percutaneous irradiation and
      surgery), and PDT was either performed as a palliative treatment for recurrence
      or in elderly patients to avoid inappropriate extensive and mutilating surgery.

PMID- 9002259
TI  - Photodynamic therapy in gynaecologic cancer.
AB  - We started photodynamic therapy in gynaecologic tumors in 1988. Seven patients
      with endometrial carcinomas stage FIGO 1a (restricted to the endometrium) were
      treated primarily and also 4 patients with recurrences of vaginal and vault
      cervix carcinoma, carcinoma of the corpus uteri and the vulva. Residual tumors
      after conventional therapy of cervix and vulvar carcinoma were treated in 2
      patients. Tumor illumination was performed by an Argon dye laser 24-72 h
      following the intravenous administration of haematoporphyrin derivatives (HPD)
      (Photosan III, 2 mg kg-1 body weight). The intracavitary tumor irradiation by
      means of a glass fibre was controlled by ultrasound. Superficial and small
      lesions of vaginal and vulvar carcinomas were subjected to superficial light
      irradiation; whereas tumors exceeding 1 cm in depth were treated interstitially.
      Tumor response was estimated 1 month after therapy. Complete remission was
      achieved in 8 patients, partial remission in 2, and no remission in 3 cases.
      Subsequent radiotherapy was performed in 3 patients with bleeding endometrial
      cancer with consecutive complete response.

PMID- 9002260
TI  - Photodynamic therapy in gynaecological neoplastic diseases.
AB  - Since 1982, our department has used photodynamic therapy (PDT) in the treatment
      of loco-regional recurrences of gynaecological cancers. We have treated 26
      patients in this time. In the majority of cases the site of vaginal recurrences
      was the vaginal vault. The light sources were an Argon-dye laser (Meditec) and,
      in some cases, a CO2 laser. The light dose ranged between 60 and 500 J cm-2. The
      photosensitizing drug used was Hematoporphyrin (HP) (Monico Farmaceutici) at the
      dose of 5 mg kg-1 body weight. Patients were evaluated 45 days after the
      treatment with a gynaecological examination and after 75-90 days with a vaginal
      smear. The results were divided into 2 groups: objective and symptomatic. The
      symptomatic response concerned only the patients treated with a palliative aim
      and, in this case, a complete response (CR) was a complete absence of symptoms at
      least for 60 days. In this group the complete response rate was 66%. In the
      curative group, the complete response was a cytological and/or histological
      absence of lesions. In this group we had 12 CR (70.58%). The survival rate was
      also evaluated. A significant review of the photodynamic therapy in
      gynaecological neoplasms has also been done.

PMID- 9002261
TI  - Photodynamic therapy in lung cancer. A review.
AB  - Photodynamic therapy (PDT) in lung cancer was introduced in 1980 to treat tumours
      located in the major airways. After systemic injection of photosensitizers,
      tumour illumination is performed using a laser fibre to transmit light of a
      specific wavelength. PDT can be performed under local anaesthesia using the
      flexible fibreoptic bronchoscope. Skin photosensitivity is the most important
      treatment morbidity caused by the prolonged cutaneous retention of
      photosensitizer molecules. Ample data have shown that PDT is effective in
      obtaining tumour necrosis, but the skin photosensitivity issue limits its
      palliative potential. Moreover, competing bronchoscopic techniques, such as
      electrosurgery, Nd-YAG laser and brachytherapy, are available and seem to be
      equally palliative for the debulking of intraluminal obstructive lung tumours.
      The curative potential of PDT in patients with roentgenologically occult lung
      cancer is the most interesting aspect of this treatment modality. A significant
      number of patients with lung cancer have limited pulmonary function. A normal
      tissue sparing treatment such as PDT may provide an alternative, as patients may
      also have subsequent multiple lung cancer primaries. Since early lung cancer
      detection is now becoming feasible, PDT may be applied to treat
      roentgenologically occult tumours with curative intent. This may optimize
      treatment efficacy in the near future.

PMID- 9002262
TI  - Photodynamic therapy of cutaneous metastases of breast cancer after local
      application of meso-tetra-(para-sulphophenyl)-porphin (TPPS4).
AB  - Nine patients with cutaneous metastases of breast cancer were treated using
      photodynamic therapy. Meso-tetra-(para-sulphophenyl)-porphin (TPPS4) was applied
      locally at a dose of 0.15-0.3 mg directly to the lesion. The light source was an
      argon dye laser emitting light of 630 nm at a fluence rate of 312-680 mW cm-2 and
      a fluence of 150 J cm-2. No signs of local or systemic side effects or toxicity
      of the photosensitizer were observed. Treatments were well tolerated with no
      photosensitivity of the skin. Complete destruction of the tumour was observed in
      three patients, reduction of the tumour size by more than 50% in two patients,
      reduction-of the tumour size by less than 50% in two patients and no regression
      in two patients. The advantages of this method include the high concentration of
      the photosensitizer in the tumour, the extremely low total dose and the lack of
      side effects. The disadvantages include the less homogeneous distribution of the
      photosensitizer in the tumour tissue compared with that obtained by intravenous
      application.

PMID- 9002263
TI  - Perspectives in cutaneous photodynamic sensitization.
AB  - The photodynamic therapy of cutaneous disease is developing more rapidly than
      that of other organs due to the accessibility of the skin to photosensitizers and
      light. The use of hematoporphyrin derivative, with its prolonged photosensitivity
      of normal skin, is gradually being replaced by a new generation of tetrapyrrolic
      photosensitizers. These are designed to absorb at longer wavelengths for deeper
      tissue penetration. Many also feature a greatly reduced photosensitizing
      potential of uninvolved skin. Another major development is the topical and
      systemic use of aminolevulinic acid for inducing the formation of endogenous
      porphyrins in cells which result in photosensitivity. This regimen is currently
      used quite extensively due to the easy availability of both drug and suitable
      light sources. However, continued investigation of the underlying mechanisms and
      their regulation will help to improve this specific photodynamic regimen.
      Currently, researchers use a whole array of therapeutic regimens and schedules
      for the evaluation of treatment efficacy. A certain uniformity of both treatment
      parameters and evaluation criteria will help to improve more rapidly our
      understanding of photodynamic sensitization in skin disease. This will also help
      us to define the right place and targeting strategies for photodynamic therapy in
      dermatology.

PMID- 9002265
TI  - Experiences of photodynamic therapy in dermatology.
AB  - From March 1988 to May 1994, 15 patients underwent the treatment protocol of
      superficial photodynamic therapy (PDT) in dermatological localized malignancies.
      Two tumours (one M. Queyrat of the penis, one basalioma) were treated primarily;
      the other 13 patients experienced relapses of underlying disease after treatment
      by surgery, radiotherapy or chemotherapy. Most of the patients (10/15) received
      doses of 2 mg Photosan III kg-1 body weight (BW), four received a lower dose of 1
      1.5 mg kg-1 BW and one patient received 3 mg kg-1 BW. Only one remarkable side
      effect (tachyarrhythmia) during Photosan III infusion occurred. All patients were
      treated by an argon dye laser system. The light dose was 200 J cm-2 (11 patients)
      and 150 J cm-2 (four patients). Complete response occurred in six lesions,
      including one M. Queyrat and five basaliomas. Two patients had significant
      partial response with distinct regression of tumour (one pretreated basalioma of
      the upper lip and one superficially spreading mesothelioma of the scrotum). Five
      patients (all basaliomas) demonstrated only local response and two patients gave
      no response (one basalioma, one melanoma metastasis). The results obtained from
      this small sample suggest the necessity of an optical dosimetric system. At
      present, PDT should be restricted for selected or pretreated cases.

PMID- 9002264
TI  - Topical photodynamic therapy in dermatology.
AB  - Although photodynamic therapy (PDT) was first used in the treatment of skin
      diseases, phase-III-clinical trials were primarily conducted for the treatment of
      bladder cancer, endobronchial and oesophageal carcinoma. In dermatology PDT has
      most extensively been used for the treatment of malignant cutaneous lesions. Up
      to now those patients have been treated systemically with first-generation
      photosensitizers. However, prolonged skin photosensitivity is a major
      disadvantage of this form of therapy. Topical PDT utilizing a variety of
      sensitizers bypass this unwanted effect. Of strong interest is 5-aminolevulinic
      acid (ALA), first introduced in the topical PDT of skin disorders in 1990 by
      Kennedy and co-workers. ALA serves as a pro-drug, i.e. the active
      photosensitizing compound is protoporphyrin IX which is synthesized in vivo after
      exogenous application of ALA. In several oncologic and non-oncologic skin
      conditions including non-melanoma skin cancer, premalignant conditions like
      actinic keratoses and in psoriasis, topical ALA-PDT showed it's effectiveness.
      Besides ALA, new sensitizers like benzoporphyrines and porphycenes may play a
      role in topical PDT. However, at the moment, there is still a need for
      comparative studies and standardized therapeutic protocols to define the place of
      topical PDT in Dermatology.

PMID- 9002266
TI  - Photodynamic therapy with systemic administration of photosensitizers in
      dermatology.
AB  - We have reviewed the results of clinical investigations into the use of
      photodynamic therapy (PDT) with intravenous injection of hematoporphyrin
      derivative (HpD), Photofrin (PF) and Sn-protoporphyrin (Sn-Pp) or oral
      administration of delta-aminolevulinic acid in the treatment of skin cancers
      and/or psoriasis. Bowen's disease was highly responsive, provided that adequate
      light and HpD or PF doses were delivered. In contrast, poor results were shown
      for squamous cell carcinoma, and the rates of complete response of basal cell
      carcinoma ranged between 0% and 100%. Treatment failures could be related to the
      delivery of low drug and/or light doses, but differences in the thickness and
      pigmentation of the treated lesions may play a relevant role. Good palliation was
      almost always achieved in patients affected by primary and secondary breast
      carcinomas, although complete eradication of tumors was very rare. PDT is a very
      promising treatment modality for both Mediterranean and HIV-related Kaposi's
      sarcoma, because it appears to be effective, can be repeated and is not
      associated with immunosuppressive activity or significant systemic toxicity. PDT
      of psoriasis with low doses of Sn-Pp, HpD or PF plus UVA light and PF plus 630 nm
      light proved to be effective and was associated with mild, dose-related and
      reversible photosensitivity.

PMID- 9002267
TI  - Electromotive diffusion (EMD) and photodynamic therapy with delta-aminolaevulinic
      acid (delta-ALA) for superficial bladder cancer.
AB  - Recent reports have shown that topical application of delta-aminolaevulinic acid
      (delta-ALA) can be used for the photodynamic diagnosis and therapy of superficial
      bladder tumours. Electromotive diffusion (EMD) increases the cellular uptake of
      polar substances. In six patients with biopsy-proven recurrent carcinoma in situ
      of the bladder after Bacillus Calmette-Guerin (BCG) treatment, 100 cm3 of a 0.5%
      delta-ALA solution at pH approximately 6 was instilled into the bladder. With a
      special Foley catheter containing a stainless steel electrode, EMD, with a 15 mA,
      pulsed current, positive polarity at the catheter, was created for 20 min in the
      sedated patient. Thereafter a laser fibre with a spheric diffuser was inserted
      into the bladder over a cystoscope. The bladder surface was irradiated at a
      wavelength of 632 nm with 350 mW s-1 (total dose, 30-50 J cm-2). Follow-up
      consisted of a cystoscopy and biopsy after 6 weeks and cystoscopy and cytology
      every 3 months thereafter. The whole procedure was well tolerated. Currently,
      five patients are tumour free after a follow-up of 10-16 months. One patient has
      recurred after 10 months with a Ta G3 superficial tumour at the bladder neck
      which was resected. In a transwell cell culture model, we investigated the effect
      of delta-ALA treatment with and without application of EMD. In this in vitro
      system, application of an electric field showed only a small increase in delta
      ALA uptake compared with uptake by passive diffusion.

PMID- 9002268
TI  - A gene encoding a protein elicitor of Phytophthora infestans is down-regulated
      during infection of potato.
AB  - Most species of the genus Phytophthora produce 10-kDa extracellular protein
      elicitors, collectively termed elicitins. Elicitins induce hypersensitive
      response in a restricted number of plants, particularly in the genus Nicotiana
      within the Solanaceae family. A cDNA encoding INF1, the major secreted elicitin
      of Phytophthora infestans, a pathogen of solanaceous plants, was isolated and
      characterized. The expression of the corresponding inf1 gene during the disease
      cycle of P. infestans was analyzed. inf1 was shown to be expressed in mycelium
      grown in various culture media, whereas it was not expressed in sporangiospores,
      zoospores, cysts, and germinating cysts. In planta, during infection of potato,
      particularly during the biotrophic stage, expression of inf1 was down-regulated
      compared to in vitro. The highest levels of expression of inf1 were observed in
      in vitro grown mycelium and in late stages of infection when profuse sporulation
      and leaf necrosis occur. The potential role of INF1 as an elicitor in
      interactions between P. infestans and Solanum species was investigated. Nineteen
      lines, representing nine solanaceous species with various levels of resistance to
      P. infestans, were tested for response to an Escherichia coli expressed INF1.
      Within the genus Solanum, resistance to P. infestans did not appear to be
      mediated by a defense response elicited by INF1. However, INF1 recognition could
      be a component of nonhost resistance of tobacco to P. infestans.

PMID- 9002269
TI  - Cloning and expression of the cutinase A gene of Botrytis cinerea.
AB  - Cutinase of Botrytis cinerea has been suggested to play an important role in
      penetration of host tissues. A protein fraction with cutin hydrolyzing activity
      was purified from culture filtrates of B. cinerea induced for cutinase activity.
      An 18-kDa protein in this fraction was identified as cutinase and the
      corresponding gene cutA was cloned. The gene is present in a single copy in the
      genome of B. cinerea strain SAS56 and its predicted amino acid sequence shows
      significant homology (31 to 35% identity) to other fungal cutinases. RNA blot
      analysis showed that cutA mRNA is induced in vitro by the cutin monomer 16
      hydroxyhexadecanoic acid and repressed by glucose. The expression of cutA during
      infection of tomato leaves is low during early phases of infection, but high when
      the fungus has colonized the leaf and starts to sporulate.

PMID- 9002270
TI  - Cutinase A of Botrytis cinerea is expressed, but not essential, during
      penetration of gerbera and tomato.
AB  - The plant pathogen Botrytis cinerea can infect undamaged plant tissue directly by
      penetration of the cuticle. This penetration has been suggested to be enzyme
      mediated, and an important role for cutinase in the infection process has been
      proposed. In this study the expression of the cutinase encoding gene cutA of B.
      cinerea was analyzed using a cutA promoter-GUS reporter gene fusion.
      Transformants containing the fusion construct were examined for GUS expression on
      gerbera flowers and tomato fruits. High GUS activity was detected from the onset
      of conidial germination and during penetration into epidermal cells, indicating
      that cutA is expressed during the early stages of infection. To determine the
      biological relevance of cutinase A for successful penetration, cutinase A
      deficient mutants were constructed by gene disruption. Pathogenicity of two
      transformants lacking a functional cutA gene was studied on gerbera flowers and
      tomato fruits. Their ability to penetrate and cause symptoms was unaltered
      compared to the wild-type strain. These results exclude an important role for
      cutinase A during direct penetration of host tissue by B. cinerea.

PMID- 9002271
TI  - Classical and molecular genetics of the model legume Lotus japonicus.
AB  - The model legume Lotus japonicus was demonstrated to be amenable to classical and
      molecular genetic analysis, providing the basis for the genetic dissection of the
      plant processes underlying nodulation and nitrogen fixation. We have developed an
      efficient method for the sexual hybridization of L. japonicus and obtained F1
      progeny derived from a cross of L. japonicus B-129-S9 Gifu x B-581 Funakura. Over
      half of the cross-pollinations resulted in fertile hybrid seed, which were
      confirmed morphologically and by single arbitrary primer DNA amplification
      polymorphisms using the DAF technique. Molecular and morphological markers
      segregated in true Mendelian fashion in a F2 population of 100 plants. Several
      DAF loci were linked using the MAPMAKER software to create the first molecular
      linkage groups of this model legume. The mapping population was advanced to
      generate a set of immortal recombinant inbred lines (F6; RILs), useful for
      sharing plant material fixed genetically at most genomic regions. Morphological
      loci for waved stem shape (Ssh), dark leaf color (Lco), and short flowering
      period (Fpe) were inherited as single dominant Mendelian loci. DAF markers were
      dominant and were detected between Gifu and Funakura at about one per primer,
      suggesting that the parents are closely related. One polymorphism (270G generated
      by single octomer primer 8.6m) was linked to a morphological locus controlling
      leaf coloration. The results demonstrate that (i) Lotus japonicus is amenable to
      diploid genetic analysis, (ii) morphological and molecular markers segregate in
      true diploid fashion, (iii) molecular polymorphisms can be obtained at a
      reasonable frequency between the related Gifu and Funakura lines, and iv) the
      possibility exists for map-based cloning, marker assisted selection and mapping
      of symbiotic mutations through a genetic and molecular map.

PMID- 9002272
TI  - Characterization of a salicylic acid-insensitive mutant (sai1) of Arabidopsis
      thaliana, identified in a selective screen utilizing the SA-inducible expression
      of the tms2 gene.
AB  - Salicylic acid (SA) plays an important signaling role in the resistance of many
      plants to pathogen invasion. Increases in endogenous SA levels have been
      associated with the hypersensitive response as well as systemic acquired
      resistance (SAR). SA also induces the expression of a subset of the pathogenesis
      related (PR) genes. However, relatively little is known about the events
      occurring subsequent to SA accumulation during a resistance response. In order to
      identify mutations in components of the SA signal transduction pathway, we have
      developed a genetic screen in Arabidopsis thaliana that utilizes the
      Agrobacterium tumefaciens tms2 gene as a counter-selectable marker. SA-inducible
      expression of the tms2 gene from the tobacco PR-1a promoter confers sensitivity
      to alpha-naphthalene acetamide (alpha-NAM), resulting in inhibition of root
      growth in germinating transgenic Arabidopsis seedlings. Mutants in which root
      growth is insensitive to alpha-NAM have been selected from this PR-1a:tms2
      transgenic line with the expectation that a subset will lack a regulatory
      component downstream of SA. The sail mutant so identified expressed neither the
      PR-1a:tms2 transgene nor the endogenous Arabidopsis PR-1, PR-2, and PR-5 genes in
      response to SA. These genes also were not induced in sai1 by 2,6
      dichloroisonicotinic acid (INA) or benzothiadiazole (BTH), two chemical inducers
      of SAR. As expected of a mutation acting downstream of SA, sai1 plants accumulate
      SA and its glucoside in response to infection with an avirulent pathogen and are
      more susceptible to this avirulent pathogen than the wild-type parent. sai1 is
      allelic to npr1, a previously identified SA-noninducible mutation. The recessive
      nature of the noninducible sai1 mutation suggests that the wild-type SAI1 gene
      acts as a positive regulator in the SA signal transduction pathway.

PMID- 9002273
TI  - Rhizobia modulate root-hair-specific expression of extensin genes.
AB  - Three cDNAs (ext3, ext127, and ext26), originally isolated by differential
      screening from a root-hair cDNA library of Vigna unguiculata, were found to
      encode extensin-like cell wall proteins. Transcripts homologous to these cDNAs
      were only detected in root hairs where mRNA levels decreased 1 day after
      inoculation with rhizobia. This coincided with the onset of root-hair
      deformation, the first morphological step in the Rhizobium-legume interaction.
      Decreases in transcript levels following inoculation with wild-type Rhizobium sp.
      NGR234 were more pronounced than with NGR delta nodABC, a mutant deficient in Nod
      factor production. Inoculation with a rhizobial strain carrying a mutation in a
      gene encoding a transcriptional activator for nod genes (NGR delta nodD1) did not
      repress mRNA levels, indicating that a second nodulation signal may be present
      that is nodD dependent. Application of purified NodNGR factors only affected
      transcript levels of ext3. The genomic locus of the gene homologous to ext26
      (Ext26G) was cloned. In the 5' flanking region, several potential TATA boxes and
      CAP signals were identified. Part of the promoter region shares homology with the
      Pisum sativum seed lectin promoter and the Nicotiana tabacum nitrate reductase
      promoter region. Nonetheless, the function of these homologous regions in gene
      regulation is unknown.

PMID- 9002274
TI  - The coat protein is required for the elicitation of the Capsicum L2 gene-mediated
      resistance against the tobamoviruses.
AB  - In Capsicum, the resistance against tobamoviruses conferred by the L2 gene is
      effective against all but one of the known tobamoviruses. Pepper mild mottle
      virus (PMMoV) is the only virus which escapes its action. To identify the viral
      factors affecting induction of the hypersensitive reaction (HR) mediated by the
      Capsicum spp. L2 resistance gene, we have constructed chimeric viral genomes
      between paprika mild mottle virus (PaMMV) (a virus able to induce the HR) and
      PMMoV. A hybrid virus with the PaMMV coat protein gene substituted in the PMMoV-S
      sequences was able to elicit the HR in Capsicum frutescens (L2L2) plants. These
      data indicate that the sequences that affect induction of the HR mediated by the
      L2 resistance gene reside in the coat protein gene. Furthermore, a mutant that
      codes for a truncated coat protein was able to systemically spread in these
      plants. Thus, the elicitation of the host response requires the coat protein and
      not the RNA.

PMID- 9002275
TI  - The Vicia faba leghemoglobin gene VfLb29 is induced in root nodules and in roots
      colonized by the arbuscular mycorrhizal fungus Glomus fasciculatum.
AB  - To investigate similarities between symbiotic interactions of broad bean (Vicia
      faba) with rhizobia and mycorrhizal fungi, plant gene expression induced by both
      microsymbionts was compared. We demonstrated the exclusive expression of 19 broad
      bean genes, including VfENOD2, VfENOD5, VfENOD12 and three different
      leghemoglobin genes, in root nodules. In contrast, the leghemoglobin gene VfLb29
      was found to be induced not only in root nodules, but also in broad bean roots
      colonized by the mycorrhizal fungus Glomus fasciculatum. In uninfected roots,
      none of the 20 nodulin transcripts investigated was detectable. VfLb29 has an
      unusually low sequence homology with all other broad bean leghemoglobins as well
      as with leghemoglobins from other legumes. It can be regarded as a novel kind of
      leghemoglobin gene not described until now and the induction of which is common
      to symbiotic interactions of broad bean with both Rhizobium and a mycorrhizal
      fungus.

PMID- 9002277
TI  - Irish Neurological Association meeting proceedings. 13-14 May 1994. Abstracts.

PMID- 9002276
TI  - Defense response in slash pine: chitosan treatment alters the abundance of
      specific mRNAs.
AB  - We used differential display to identify chitosan responsive cDNAs in slash pine
      cell cultures. Two clones that showed increased mRNA abundance had sequence
      similarity to genes with roles in major plant defense responses, clone 18 to
      cinnamic acid 4-hydroxylase, and clone 30 to chitinase.

PMID- 9002278
TI  - Sylvester O'Halloran Surgical scientific meeting. March 8-9, 1996. Abstracts.

PMID- 9002279
TI  - [International Congress of Family and Community Medicine. Granada, 13-16 November
      1996, Abstracts].

PMID- 9002280
TI  - XLIX National Congress of the Italian Society of Anatomy. Bari, 2-5 October 1995.
      Abstracts.

PMID- 9002281
TI  - L National Congress of the Italian Society of Anatomy. Catania, 24-27 September
      1996. Abstracts.

PMID- 9002282
TI  - Index, volumes 1-38, 1957-1994.

PMID- 9002284
TI  - The XXIVth National Immunology Conference. Bucharest, 25 September 1995.
      Abstracts.

PMID- 9002283
TI  - [National meeting of the Mexican Association of Gastroenterology. Monterrey,
      Mexico, 30 November-5 December 1996. Abstracts].

PMID- 9002285
TI  - Anniversary scientific session. Bucharest, September 17-19, 1996. Abstracts.

PMID- 9002286
TI  - Developmental pharmacology: past, present and future.

PMID- 9002287
TI  - Hospital facilities available to patients with Kawasaki disease: results of a
      national survey of Kawasaki disease in Japan.
AB  - Since 1970, thirteen nationwide epidemiologic surveys of Kawasaki disease have
      been conducted, and questions on the current situation of hospitals and their
      facilities have been included in the survey form to assess the care available to
      patients with Kawasaki disease. To clarify the characteristics of medical care
      for Kawasaki disease, this paper summarizes the present condition of hospital
      facilities available to patients with Kawasaki disease. A questionnaire form
      including questions about the situation of hospital facilities was sent to all
      pediatric departments of hospitals with 100 or more beds throughout Japan. The
      proportion of hospitals in which successive observations with echocardiography
      (UCG) is available (UCG available hospital) was significantly increased compared
      with the ninth survey (1985-86), whereas that of the hospitals in which coronary
      angiography (CAG) is available (CAG available hospital) was significantly
      decreased. Almost all (96.2%) of the patients were reported from the UCG
      available hospitals. The proportion of patients reported from hospitals with a
      set policy for intravenous gamma globulin (IVGG) therapy was 74.5%. The
      proportion of UCG available and CAG available hospitals and that of hospitals
      with a set policy for IVGG therapy correlated with the increase in the number of
      patients. In conclusion, hospital facilities available to patients with Kawasaki
      disease in Japan have satisfactory capability for diagnosis and management of
      Kawasaki disease.

PMID- 9002288
TI  - Clinico-epidemiological features of infantile hydrocephalus in Japan.
AB  - In 1988, a nationwide survey was conducted in Japan, in order to examine the
      prevalence and clinico-epidemiological features of hydrocephalus that developed
      before 1 year of age. The study was based on questionnaires that were sent to all
      hospitals in Japan with more than 200 beds. There were 1435 patients who were
      eligible for the analysis. They were born before 1987 and diagnosed as having
      infantile hydrocephalus. Approximately two-thirds of the patients had primary
      hydrocephalus. Neural tube defects were the most frequent cause of the primary
      hydrocephalus and common among full-term infants. On the other hand, secondary
      hydrocephalus occurred more often in preterm infants, mainly following
      intracranial hemorrhage. Intracranial hemorrhage as a cause of hydrocephalus
      increased over the year, while the incidence of hydrocephalus secondary to
      intracranial infection decreased during the same period.

PMID- 9002289
TI  - Motor nerve conduction studies on children with spinal muscular atrophy.
AB  - Median and posterior tibial motor nerve conduction studies were performed on 10
      children with spinal muscular atrophy (SMA). Three patients with SMA type I, in
      whom rapid deterioration occurred, showed reduced motor nerve conduction velocity
      and a remarkably low M-wave amplitude in both nerves. In type II and III
      patients, the motor nerve conduction velocity was normal in the median nerve,
      although the M-wave amplitude was small in the tibial nerve. In four patients, a
      reduction of the M-wave amplitude was observed as clinical symptoms advanced.
      These findings may suggest that motor conduction studies in spinal muscular
      atrophy provide complementary information for understanding the pathogenesis and
      are also useful to clarify the heterogeneity of this disease.

PMID- 9002290
TI  - Developmental changes in electroencephalogram for term and preterm infants using
      an autoregressive model.
AB  - The purpose of the present study was to clarify the developmental changes of
      electroencephalogram (EEG) background activity in term and preterm infants that
      take place with increasing conceptional age (CA) through an autoregressive (AR)
      model. Polygraphical EEG recordings were obtained from 76 healthy term and
      preterm infants with a CA ranging between 31 and 40 weeks. Decreases in total
      power and component power of delta were noted with CA during burst activity (BA)
      in quiet sleep (QS) and during active sleep (AS). Increases in total power and
      component power of delta were noted with CA during interburst interval activity
      (IBIA) of QS. Regression analysis (RA) of the information amount (IA) indicated a
      negative correlation with increasing CA in AS and in the monopolar EEG tracings
      Fp1, C3, O1 and O2 in BA, and a positive correlation in O1 in IBIA. Regression
      analysis of the IA of delta indicated a negative correlation with increasing CA
      in AS and in Fp1, C3, O1 and O2 in BA, and a positive correlation in O1 in IBIA.
      Regression analysis of the IA of delta indicated a negative correlation with
      increasing CA in BA and AS. These results showed that the high voltage slow wave
      component changed to a low voltage slow one with development in AS and that BA
      was longer in duration and lower in power with increasing CA, while IBIA was
      shorter in duration and higher in power. In conclusion, significant developmental
      changes occur in all derivatives of AS. Even though the EEG of BA and IBIA change
      separately, they are followed by EEG of QS in a continuous pattern.

PMID- 9002291
TI  - Distribution of human herpesvirus 6 and varicella-zoster virus in organs of a
      fatal case with exanthem subitum and varicella.
AB  - The distribution of human herpesvirus 6 (HHV-6) and varicella-zoster virus (VZV)
      was examined in autopsy samples from a fatal case with both virus infections. A 9
      month-old boy developed convulsive seizures followed by macular skin rashes,
      rapidly progressed to brain death, and died 15 days after the onset, when signs
      of varicella were noted. An isolation of HHV-6 from blood and evaluation of
      antibody activities to various viral agents including HHV-6 were performed before
      his death. Postmortem examinations included: (i) isolation of HHV-6 and VZV from
      tissues or organs; (ii) detection of both virus antigens in tissues or organs by
      an indirect immunofluorescent assay using monoclonal antibodies to both viruses;
      (iii) amplification of both viruses and human herpesvirus 7 DNA sequences by a
      nested polymerase chain reaction assay; and (iv) endonuclease digestion of
      amplified products of HHV-6 DNA for differentation of variants A and B. Human
      herpesvirus 6 DNA was detected in peripheral blood mononuclear cells (PBMC) and
      plasma obtained at the eruptive stage but present only in PBMC 15 days after,
      indicating the primary infection with HHV-6, although the virus was not isolated
      from the same blood sample and a significant rise in the antibody titers to HHV-6
      was not observed. Both virus antigens and DNA were detected in various tissues or
      organs obtained at autopsy, but only VZV was isolated from these samples,
      suggesting disseminated infection with both viruses in an infant. All the
      amplified products of HHV-6 DNA were variant B. Among the findings for the
      distribution of virus antigens, it was noteworthy that HHV-6 antigen was
      demonstrated in the endothelial cells of small vessels in the frontal lobe of the
      brain. There was no evidence of HHV-7 infection. These data indicate that the
      primary HHV-6 infection closely followed by the primary VZV infection had the
      potential hazard of an unexpected and apparently life-threatening event, in which
      disseminated infections with both viruses were noted in multiple tissues or
      organs including the brain.

PMID- 9002292
TI  - White blood cell count, C-reactive protein and erythrocyte sedimentation rate in
      respiratory syncytial virus infection of the lower respiratory tract.
AB  - Laboratory findings such as white blood cell (WBC) count, C-reactive protein
      (CRP) concentration and erythrocyte sedimentation rate (ESR) level in patients
      with bronchiolitis, bronchopneumonia and lobar pneumonia caused by respiratory
      syncytial virus (RSV) were studied. The diagnosis of having RSV infection of the
      lower respiratory tract was made on the presence of RSV antigen in nasopharyngeal
      specimens by means of enzyme immunoassay, on chest X-ray appearances and clinical
      manifestations. The WBC counts in the lobar pneumonia cases (n = 25, 12,288 +/-
      6296/mm3) were significantly greater than those for the bronchiolitis (n = 52,
      9562 +/- 2720/mm3) and bronchopneumonia (n = 43, 8369 +/- 3714/mm3) cases. The
      concentrations of CRP in lobar pneumonia cases (n = 25, 6.5 +/- 7.3 mg/dL) were
      significantly greater than those in the bronchiolitis (n = 52, 1.9 +/- 2.0 mg/dL)
      and bronchopneumonia (n = 43, 2.1 +/- 2.4 mg/dL) cases. The ESR levels in the
      lobar pneumonia cases (n = 24, 43.8 +/- 29. mm/h) were also significantly higher
      than those in the bronchiolitis (n = 34, 20.1 +/- 12.3 mm/h) and bronchopneumonia
      (n = 40, 24.7 +/- 15.9 mm/h) cases. There were no significant differences in the
      WBC counts, the CRP concentrations and ESR levels between the bronchiolitis and
      bronchopneumonia cases. These results suggest that the RSV lobar pneumonia cases
      are coinfected with some bacterial organisms more heavily than in the RSV
      bronchiolitis and bronchopneumonia cases.

PMID- 9002293
TI  - Survey of family history on allergy in 1-year-old and 6-year-old children.
AB  - A retrospective survey of a family history of allergy employing a special
      questionnaire for children was performed. The survey included 1-year-old (n =
      267) and 6-year-old children (n = 410) with allergies as well as 1-year-old (n =
      313) and 6-year-old children (n = 329) without allergies. An 'Allergy Risk Score'
      (ARS) for each subject was calculated according to the history of allergy in
      three family members: father, mother and a sibling. Each family member was scored
      as 2.0 (overt history of allergies), 1.0 (provable), 0.5 (possible) or 0
      (absent), and the ARS of the subjects was calculated as the total of the family
      members' scores. The ARS of children in the allergy groups was statistically
      higher than that of the control groups in both age groups. The ARS increased with
      an increase in the odds ratio (an approximate value of the risk), especially in 6
      year-old children. An ARS calculated on the basis of family history could be a
      useful and practical index for estimating the risk of allergy development in
      children, and may be helpful in predicting and preventing allergies in infants
      and children.

PMID- 9002294
TI  - Childhood asthma and atmospheric conditions.
AB  - Bronchial asthma is the most common chronic respiratory illness in childhood. It
      is characterized by paroxysmal bronchospastic periods. There are many studies
      giving reasons to explain the bronchospasm periods. One of the reasons,
      atmospheric conditions, is effective in creating a clinical picture of asthmatic
      patients. In the present study, the correlation between atmospheric conditions
      and asthmatic symptoms in children was investigated using peak expiratory flow
      rate (PEFR) as the respiratory function test. Twenty-one children with bronchial
      asthma were monitored in the study. They were followed as outpatients of the Ege
      University Medical Faculty, Department of Pediatric Allergy and Pneumotology,
      between November 1993 and June 1994. Atmospheric conditions were recorded from
      the local meteorology center. Complaints and the PEFR of children were compared
      with the meteorological data. Asthmatic symptoms were increased by low
      temperatures in all asthmatic children. An increase was detected in the extrinsic
      group by relative humidity and ratio of cloud, but in the intrinsic group only by
      relative humidity.

PMID- 9002295
TI  - Autonomic nervous system functions in childhood essential hypertension.
AB  - The etiopathology of essential hypertension (EH) is still controversial,
      different pathologic mechanisms have been estimated as a cause of EH. One of
      these mechanisms is autonomic nervous system dysfunction (ANSD). Although there
      are different studies showing ANSD in adult EH, limited studies on ANSD in
      childhood EH are present. The present study was planned to investigate the role
      of ANSD in childhood EH. The study group (SG) consisted of 24 children with EH
      and the control group (CG) was 24 healthy children. Non-invasive autonomic
      nervous system function tests: the orthostatic test, Valsalva ratio, 30/15 ratio
      and heart rate responses to deep breathing were performed on members of both
      groups. The mean differences in systolic blood pressure between supine resting
      and standing positions in the study and control groups were significant (z = 
      2.577, P = 0.0051). The mean differences in diastolic blood pressure between
      supine resting and standing positions in SG and CG were found to be statistically
      meaningful (z = -2.722, P = 0.0033). The mean differences in heart rate variation
      during hyperventilation in SG and CG were significant (z = -2.54, P = 0.0055).
      The mean differences in the Valsalva ratio between SG and CG were not
      statistically meaningful (z = 1.52, P = 0.0643). The mean differences in the
      30/15 ratio in SG and CG were not found to be significant (z = -1.455, P =
      0.0735). In the light of these results, both sympathetic and parasympathetic
      autonomic nervous system dysfunction in childhood essential hypertension were
      found.

PMID- 9002296
TI  - Renal functional measurements in young rats with chronic inhibition of nitric
      oxide synthase.
AB  - The purpose of the present study was to examine renal functional changes caused
      by chronic blockade of nitric oxide (NO) synthesis in young rats. Two types of NO
      synthase inhibitor were used: NG-nitro-L-arginine methyl ester (L-NAME) as a non
      selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the
      inducible isoform. Oral administration of L-NAME (20-80 mg/dL of drinking water),
      not AG (400 mg/dL), for 4 weeks induced systemic hypertension in the treated
      rats. Both inhibitors caused a significant reduction in urinary excretion of NO2
      /NO3-. Rats treated with L-NAME developed proteinuria and tubular enzymuria (high
      excretion of N-acetyl-beta-D-glucosaminidase) in a dose-dependent fashion, with
      normal serum levels of creatinine, albumin and cholesterol. Chronic AG
      administration did not alter the urinary levels of protein and N-acetyl-beta-D
      glucosaminidase or serum laboratory values. Overall, these observations highlight
      the importance of the continuous generation of NO by the constitutive isoform in
      the control of vascular tone and the maintenance of renal glomerular and tubular
      function. Oral administration of L-NAME may serve as a model of chronic NO
      deficient hypertension with renal injury in young rats.

PMID- 9002297
TI  - Change of renal function during vancomycin therapy in extremely low birthweight
      infants.
AB  - Twenty extremely low birthweight infants were treated with vancomycin (VCM).
      Their gestational age was 26.3 +/- 1.4 weeks (range 24.0-28.7 weeks) and their
      birthweight was 829 +/- 133 g (range 562-900 g). At the time of initial
      administration of VCM, postnatal age was 29.5 +/- 15.8 days (range 5-54 days).
      Vancomycin was administered in a dose between 9.3 and 11.0 mg/kg every 12 h for a
      period of 6.3 +/- 2.4 days (range 4-13 days). Serum and urinary specimens were
      obtained before and after (within 24 h following the last dose) VCM therapy.
      Serum creatinine and sodium, and urinary N-acetyl-beta-D-glucosaminidase (NAG)
      activity, creatinine, sodium, and beta-2-microglobulin (BMG) concentrations were
      measured. Fractional excretion of sodium (FENa) and NAG index (NAG:creatinine
      ratio) were calculated. There were no significant differences between the before
      and after VCM treatment in serum creatinine, urinary BMG concentration, FENa and
      NAG index. No infant showed any symptoms of renal insufficiency. However, the NAG
      index and FENa increased after treatment in 1 of 20 infants. Vancomycin is
      effective and safe in the treatment of serious infections in extremely low
      birthweight infants.

PMID- 9002298
TI  - Pathological improvement of IgA nephropathy and Henoch-Schonlein purpura
      nephritis with urokinase therapy.
AB  - The pathological findings of 13 patients with immunoglobulin A (IgA) nephropathy
      or Henoch-Schonlein purpura nephritis before and after urokinase (UK)
      administration were investigated retrospectively. The mean activity index value
      decreased significantly at the time of the second biopsy compared with that of
      the biopsy before UK treatment. The mean chronicity index value, which was
      considered to reflect the renal outcome, before and after UK treatment did not
      change significantly, although it improved significantly in six patients.
      Immunofluorescence microscopy showed that the immune deposition of C3 decreased,
      but that of IgA and fibrin-related antigen were unchanged, by UK therapy. These
      results suggest that UK may prevent the mesangial proliferation associated with
      IgA nephropathy and Henoch-Schonlein purpura nephritis not only by its
      fibrinolytic action, but also by other mechanisms, such as digestion of the
      mesangial matrices.

PMID- 9002299
TI  - Comparison of two fetal growth curves in screening for high-risk neonates.
AB  - The International Statistical Classification of Diseases and Related Health
      Problems (ICD-10) defines the 10th percentiles on the fetal growth curve as the
      cutoff point for light- and small-for-gestational-age infants, instead of the
      mean bodyweight -1.5 standard deviation (SD) on the fetal growth curve, which has
      been used in Japan since 1983. Data on a 5260 sample of term neonates who were
      born during the 30-month period between January 1993 and June 1995 were obtained.
      The clinical usefulness of the 10th percentiles and mean bodyweight -1.5 SD
      cutoff on the fetal growth curve as screening criteria for high-risk neonates of
      light- and small-for-gestational-age infants was evaluated. There was a
      statistically significant higher morbidity rate among the neonates whose
      birthweight was below mean bodyweight -1.5 SD than for those whose birthweight
      was below the 10th percentile cut off. But there was no significant difference
      between the morbidity rate of neonates whose birthweight was between mean
      bodyweight -1.5 SD and the 10th percentile cutoff and the morbidity rate of
      neonates whose birthweight was above the 10th percentile cutoff. Therefore, mean
      bodyweight -1.5 SD on the fetal growth curve is a more effective means of
      screening for high-risk light- and small-for-gestational-age infants than the
      10th percentile cutoff on the fetal growth curve.

PMID- 9002300
TI  - The usefulness of measuring body fat deposition for detecting obesity and
      atherogenesity in Japanese school children.
AB  - Body fat deposition was measured in overweight and non-overweight children using
      a bioelectrical impedance method, and its relationship with serum lipids and
      apolipoproteins was investigated in 90 overweight children (over 120% of their
      ideal weight) and 241 non-overweight children aged 10-15 years in Niigata
      Prefecture. The results were as follows. Overweight boys had significantly higher
      levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C),
      atherogenic index (AI), RLP-cholesterol (RLP-C), apoA1, apoA2, apoB, apoC2,
      apoC3, apoE and the ratio of apoB to apoA1 than non-overweight boys. Overweight
      girls had significantly higher levels of TC, LDL-C, AI, remnant-like lopoprotein
      cholesterol (RLP-C), apoA2, apoB, apoC2, apoC3, apoE and the ratio of apoB to
      apoA1 than non-overweight girls. It has been reported that of all children
      studied 2.1% had higher levels of RLP-C than its upper limit known for adults (12
      mg/dL). Of the overweight children in the present study, 4.4% had a high level of
      RLP-C whereas only 1.2% of non-overweight children had a high RLP-C level. No
      difference in the lipoprotein levels was found between overweight and non
      overweight children. In both boys and girls, relative weight, body fat, skinfold
      thickness and body mass index (BMI) were correlated with the lipoprotein levels.
      Non-overweight boys whose body fat was over 20% had significantly higher levels
      of TC, LDL-C, apoA2, apoB, apoC2, apoE and apoB/A1 than those whose body fat was
      less than 20%. It was concluded that the measurement of body fat deposition,
      together with relative weight, was useful for detecting obesity and
      atherogenesity in Japanese school children.

PMID- 9002301
TI  - Testicular morphological changes in children with acute lymphoblastic leukemia
      following chemotherapy.
AB  - Morphological changes in the testis induced by chemotherapy given according to
      the Tokyo Children's Cancer Study Group (TCCSG) regimens were studied in children
      with acute lymphoblastic leukemia (ALL). After informed consent, testicular
      biopsies were performed 14 times in 12 patients at the end of treatment. The
      testicular morphology in all cases had sustained a degree of damage. The tubular
      fertility index (TFI), calculated as the percentage of seminiferous tubules
      containing identifiable spermatogonia, was from 0 to 42.8% (mean 33.4%) below the
      normal value. Infiltration of leukemic cells was the most significant factor
      contributing to the decrease in TFI. There were no differences in the TFI among
      the TCCSG protocols. Formation of sperm was recognized in six cases, whose ages
      were 7, 8, 9, 10, 15 and 19 years. In two children, testicular biopsy was
      performed twice. In the second biopsy, TFI was elevated and sperm formation with
      the maturation of Leydig cells was observed. A number of other pathological
      changes were observed: modification of spermatogonia, Sertoli cells and inclusion
      bodies in spermatogonia, abnormal maturation of Leydig cells, evidence of
      interstitial fibrosis and thickening of the basement membrane. These results
      suggest that recent strong chemotherapy for the treatment of ALL might cause
      severe but not fatal damage to children's testicular tissue. As chemotherapy
      escalates, more investigation of testicular function will be necessary.

PMID- 9002302
TI  - Treatment of aplastic anemia with antithymocyte globulin, cyclosporin A,
      methylprednisolone, danazol and recombinant human granulocyte-colony stimulating
      factor.
AB  - The main purpose of the present study was to determine the response rate to
      immunosuppressive therapy combined with recombinant human granulocyte-colony
      stimulating factor (rhG-CSF) and its efficacy for preventing infections in
      patients with severe aplastic anemia. The treatments included one course of
      antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF.
      Three patients had very severe aplastic anemia and two had moderate aplastic
      anemia. One patient relapsed 13 months following the first course of therapy and
      received a second course. Five patients received six courses of treatment and the
      response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil
      count of greater than 1.0 x 10(9)/L within 40 days. All patients with a complete
      response are transfusion-free and doing well. All five patients are currently
      alive and have not had any episode of infection for 17-53 months. The results of
      the study indicate that this therapy may improve the poor prognosis of young
      patients with severe aplastic anemia. It has a good response rate and induces a
      rather rapid increase in the neutrophil count, which protects against life
      threatening bacterial and fungal infections.

PMID- 9002303
TI  - Listener and context dependency in the perception of emotional aspects of infant
      voice.
AB  - Developmental aspects of an infant's ability to express emotions through
      vocalizations were studied based on perceptual rating experiments against 12
      vocalization- and emotion-related reference words. Three groups of listeners,
      students, mothers with infants, and nursery governesses, rated 28 voice samples
      recorded from a male infant at 6, 9, 12 and 17 months of age, under a positive or
      negative context. Among three factors extracted by a factor analysis, one
      representing the emotional contrast of frightened/angry versus happy was found to
      be independent of listener group, infant age and context. The other two, one
      representing contrast between pleased/happy versus demanding/sad and the other
      seeking affection and rejecting/angry were dependent on infant age and context.
      These results may indicate that infants even at 6 months of age can express the
      emotional contrast of 'pleasure' versus 'discomfort' through vocalization, which
      listeners perceive independently in context.

PMID- 9002304
TI  - Left and right ventricular volume characteristics in tetralogy of Fallot and
      their relationship to arterial oxygen saturation and age.
AB  - Left (LV) and right ventricular (RV) volume characteristics in 43 patients with
      tetralogy of Fallot (TOF) undergoing no prior surgical intervention, aged 3-50
      months, were evaluated. The control group consisted of 45 patients with Kawasaki
      disease without cardiac lesions, aged 12-82 months. The TOF patients were divided
      into four groups: those having arterial oxygen saturation < 80% with an age at
      the time of study < 18 months (group 1a) or with that > or = 18 months (group
      1b), and those with arterial oxygen saturation > or = 80% with an age < 18 months
      (group 2a) or with that > or = 18 months (group 2b). The results were compared
      with those in control subjects. In group 1a, each of LV end-diastolic volume
      (EDV), LV ejection fraction (EF), RVEDV and RVEF was reduced. In group 1b, LVEDV,
      LVEF and RVEF were decreased. In groups 2a and 2b, RVEF alone was depressed. From
      these results, the severity of hypoxemia was an important risk factor for
      ventricular dysfunctions. No influence of age on the volume characteristics was
      found. The investigations suggested that patients with TOF having an arterial
      oxygen saturation < 80% are probably candidates for early surgical intervention.

PMID- 9002305
TI  - Gas chromatographic-mass spectrometric metabolic profiling of patients with fatal
      infantile mitochondrial myopathy with de Toni-Fanconi-Debre syndrome.
AB  - The metabolic profiles of three patients with fatal infantile mitochondrial
      myopathy with de Toni-Fanconi-Debre syndrome were studied by simultaneous
      analysis, after urease treatment of urinary organic acids, carbohydrates, polyols
      and amino acids using gas chromatography/mass spectrometry (GC/MS). All three
      patients persistently showed lactic aciduria, phosphaturia, glucosuria and
      generalized amino aciduria. This abnormal urinary metabolic profile was observed
      before the onset of any clinical symptoms, indicating that chemical diagnosis may
      be done presymptomatically. In one patient, the concentration of lactate
      increased in parallel with the severity of the clinical condition, whereas the
      urinary levels of 3-hydroxybutyrate, amino acids and glucose fluctuated and
      showed only a general tendency to increase with the clinical course. The above
      results suggest that simultaneous GC/MS analyses, without fractionation, of
      urinary metabolites facilitate not only the early chemical diagnosis either
      before or after the first onset, but also follow-up studies, providing an
      important index for the evaluation of the severity and clinical course in
      patients with this disorder.

PMID- 9002306
TI  - Epidemiology of poliomyelitis in Karachi, Pakistan: prospective studies during
      1990-93.
AB  - Between October 1989 and September 1993, 245 cases of poliomyelitis visited the
      Department of Pediatrics, Civil Hospital Karachi, Pakistan. The majority of them
      were between 6 months and 2 years of age and the epidemic occurred during the hot
      season. The dominant serotype was polio type 1. All of the polioviruses isolated
      from the patients were wild type. Virological studies also disclosed that
      enteroviruses other than polioviruses were prevalent among healthy children as
      well as diarrheal and polio patients. Serodiagnosis by poliovirus-specific
      immunoglobulin M antibody tests using the capture enzyme-linked immunosorbent
      assay method were in good agreement with the results of virus isolation. The
      present study demonstrated that Pakistan is a region endemic for wild poliovirus
      and more aggressive preventive measures are needed to eradicate poliomyelitis
      from the region.

PMID- 9002307
TI  - Enteric pathogens in severe forms of acute gastroenteritis in Ghanaian children.
AB  - Diarrheal disease is the major cause of childhood morbidity in developing
      countries. Although malnutrition is known as a risk factor for severe
      gastroenteritis, the role of enteric pathogens in the clinical severity is
      unclear. The present study was conducted in well nourished Ghanaian preschool
      children during a 3 month period of the rainy season to assess the relationship
      between enteric pathogens and severe gastroenteritis. Two hundred and twenty-five
      children with acute gastroenteritis and 64 age-matched control children were
      prospectively examined for the severity of dehydration and enteric pathogens in
      their stools. Of the 225 children with gastroenteritis, 69.8% (157/225) had mild
      dehydration and 30.2% (68/225) had severe dehydration. Bacteria were similarly
      isolated in stool samples from children with mild and severe dehydration and
      controls. Rotavirus accounted for 20.6% of children with severe dehydration and
      was more often isolated in stools from patients with severe dehydration than
      those from controls. Furthermore, the mixed infections associated with rotavirus
      and bacteria were more often found in patients with severe dehydration than those
      with mild dehydration or controls. Parasites were similarly found at low
      incidences among the three groups. The present study implied that rotavirus was
      more responsible for severe gastroenteritis than bacteria or parasites. However,
      factors other than enteric pathogens must be sought in a considerable number of
      severe cases. A large scale study throughout a year is recommended to obtain more
      precise information that would reflect the seasonal variation of rotavirus
      infections.

PMID- 9002308
TI  - Chronic respiratory failure after acquired cytomegalovirus infection in a very
      low birthweight infant.
AB  - The case of a female infant who developed chronic respiratory failure after an
      acquired cytomegalovirus (CMV) infection is presented here. She was a very low
      birthweight (VLBW) infant and was free from oxygen supplement until 2 months
      after birth. Interstitial pneumonia occurred at 2 months of age, and her
      respiratory condition gradually deteriorated. A chest roentgenogram at 4 months
      revealed hyperinflation and reticular shadow, similar to that of severe chronic
      lung disease (CLD) in preterm infants. She was mechanically ventilated because of
      progressive respiratory deterioration, and oxygen dependency continued for 5
      months after extubation. There are several previous reports of CMV pneumonia in
      term neonates or infants. However, there appears to be no published report on the
      pulmonary sequelae of CMV pneumonia in VLBW infants. The present case seems to
      indicate that acquired CMV pneumonia in VLBW infants causes chronic respiratory
      failure even when mechanical ventilation is not administered, and this
      respiratory failure is very similar to CLD in clinical symptoms and chest
      roentgenogram.

PMID- 9002309
TI  - Systemic air embolism in an extremely low birthweight infant treated with high
      frequency oscillatory ventilation.
AB  - An extremely low birthweight infant in whom systemic air embolism occurred during
      high-frequency oscillatory ventilation is reported. He was delivered at 25 weeks
      and 6 days gestation weighing 600 g. He was diagnosed as having respiratory
      distress syndrome and had intermittent mandatory ventilation. At 2 days of age,
      there was pulmonary hemorrhage and high-frequency oscillatory ventilation was 22
      cmH2O. At 9 days of age, X-ray film revealed air in the intracardiac cavity and
      major systemic vessels. Systemic air embolism can occur in an extremely low
      birthweight infant having high-frequency oscillatory ventilation with a mean
      airway pressure of 22 cmH2O or higher.

PMID- 9002310
TI  - Giant cerebral arterial aneurysm in an infant: report of a case and review of 42
      previous cases in infants with cerebral arterial aneurysm.
AB  - A giant cerebral aneurysm with subarachnoidal hemorrhage in a 4-month-old female
      infant is reported. The clinical course was complicated by an electrolyte
      imbalance and unexpected intoxication by phenobarbital. She died as a result of
      the third episode of rerupture of the aneurysm on the 16th day after onset.
      Histological findings showed that the aneurysm was of the saccular type, 35 x 20
      x 22 mm in size, arising from the basilar artery. The aneurysmal wall consisted
      microscopically of fibrous tissue with partial absence or fragmentation of the
      internal elastic lamina and muscular lamina. Forty-three cases of cerebral
      aneurysms during the first year of life including the present case were
      summarized and it was found that they could be characterized as follows: (i) a
      high incidence of onset in early infancy; (ii) larger than 10 mm; (iii) a large
      number arose from the posterior circulation of the circle of Willis; and (iv) a
      poor prognosis of non-operated groups, especially in the posterior circulation.

PMID- 9002311
TI  - Congenital chylothorax in a patient with 21 trisomy syndrome.
AB  - A female infant with 21 trisomy syndrome associated with congenital chylothorax
      was reported. She was born at a gestational age of 34 weeks by Cesarean section
      because of fetal hydrothorax and hydrops fetus, confirmed by ultrasonography at
      32 weeks. Emergent resuscitation and immediate thoracentesis were performed soon
      after birth. After beginning breast feeding, the serous pleural fluid became
      opalescent and a diagnosis of congenital chylothorax was made. Feeding was
      changed to medium-chain triglyceride (MCT) feeding and the production of pleural
      effusion disappeared after thoracentesis was performed several times.
      Accumulating evidence suggested that MCT feeding and intermittent thoracentesis
      under echo guide were effective. Some reports on patients, including this one,
      suggest that there may be more patients with 21 trisomy associated with
      congenital hydrothorax. Therefore, congenital hydrothorax might be listed as a
      complication of 21 trisomy.

PMID- 9002312
TI  - Comparison of specific immunities to varicella-zoster virus following post
      exposure prophylaxis of varicella by oral acyclovir observed in a family.
AB  - An otherwise healthy 3-year-old girl developed severe varicella complicated by
      aseptic meningitis and received intravenous acyclovir (ACV) therapy. Her two
      siblings who were susceptible to varicella-zoster virus (VZV) and closely exposed
      to VZV in the family received oral ACV (45 or 54 mg/kg per day in four divided
      doses for 7 days) starting 8 days after onset of the index case for post-exposure
      prophylaxis of varicella. They showed only five or seven papules over the body
      without fever 12 days after onset of the index case, while they had one-third or
      half the level of antibody titer and equal sized skin reactions to VZV antigen of
      the index case 2.5 months later.

PMID- 9002313
TI  - Neurally mediated syncope complicated with paroxysmal atrial fibrillation.
AB  - Recently, it has come to be accepted that the result of the tilt test is specific
      to neurally mediated syncope (vasovagal syncope). Only rarely is a case of
      paroxysmal atrial fibrillation without any organic diseases in childhood
      reported. A case reported here of a 14-year-old boy with neurally mediated
      syncope; which was complicated by paroxysmal atrial fibrillation, and which was
      diagnosed by performing the tilt test. Atrial fibrillation can be induced by the
      extraordinary stimulation of the vagal nerve during syncope. In a child, neurally
      mediated syncope complicated with paroxysmal atrial fibrillation has not been
      previously reported.

PMID- 9002314
TI  - Apparently increased trough levels of tacrolimus caused by acute infantile
      diarrhea in two infants with biliary atresia after liver transplantation.
AB  - Two infants with biliary atresia who exhibited three-fold increased trough levels
      of tacrolimus and required reduced doses during episodes of acute infantile
      diarrhea within 5 months of liver transplantation are described. The cause of the
      increase was not explained simply by hemoconcentration as a result of significant
      loss of extracellular fluid during these episodes. It does highlight an important
      issue: that of the continuing need to carefully monitor the trough levels of
      tacrolimus in such infants.

PMID- 9002315
TI  - Treatment of atopic dermatitis in children: the importance of skin care and
      environmental control.
AB  - A 5-year-old female with severe atopic dermatitis with secondary bacterial
      infection is presented. The patient had been managed with topical steroids and
      anti-allergic drugs for several months prior to admission to the National
      Children's Hospital, Tokyo. This case is reported to emphasize that drugs alone
      are not sufficient in treating severe atopic dermatitis. Skin care and
      environmental control are equally important and should form a part in the
      management of the disease.

PMID- 9002316
TI  - Epidermal growth factor in tracheal aspirates of ventilated premature infants.

PMID- 9002317
TI  - Deaf adults' attitudes toward career choices for deaf and hearing people in
      India.
AB  - This study investigated the expressed attitudes of deaf people in India toward
      career choices for deaf and hearing people. Deaf adults from Pune, India rated
      the suitability of 12 professions for deaf and hearing people and gave written
      comments on the suitability of any other professions they could list. The
      results, in general, were consistent with those of other studies in the United
      States, England, Italy, South Africa, and India with hearing teachers and parents
      of deaf children, which indicated that the hearing status of imagined deaf and
      hearing advisees selectively influenced attitudes toward the suitability of
      certain professions. Some differences in profession preferences also emerged
      indicating that the deaf respondents' criteria for career choice appeared to be
      primarily based on the use of hearing, speech, and visual skills required for a
      particular career. There was some suggestion that culturally specific factors
      played a role in shaping attitudes. These findings underscore the importance of
      understanding the attitudes of deaf people.

PMID- 9002318
TI  - Deaf students' recall of Spanish vocabulary under three testing conditions.
AB  - This investigation examined the effects of three training conditions on deaf
      students' recall of Spanish word meaning as measured by performance on a Spanish
      vocabulary test. The conditions were; a) repeated written productions, b)
      repeated fingerspelling, and c) repeated silent reading of selected Spanish words
      and their English equivalents. Subjects were 30 deaf undergraduate students
      enrolled in introductory Spanish courses at Gallaudet University in Washington,
      DC. Researchers assigned 10 subjects to each of the 3 training groups. A 30 item
      pretest was administered to verify that the vocabulary was not known to the
      subjects. A posttest containing 25 items from the pretest was administered twice
      to the subjects. For short-term memory there were no statistically significant
      differences across the 3 conditions. For long-term memory scores under the
      repeated written condition were significantly higher than scores under
      fingerspelling and silent reading conditions. The use of a study strategy
      incorporating writing may enhance the learning of Spanish vocabulary by deaf
      college students. The strategy could also be applied to other foreign languages
      and a range of academic subjects for deaf students.

PMID- 9002319
TI  - Classroom assessment of the use of compact language drills: a technique borrowed
      from foreign language teaching.
AB  - Many deaf children have great difficulty learning how to use irregular English
      verbs. This research study seeks to exemplify how a single-case, ABA design can
      be used by classroom teachers in making a determination about the usefulness of
      classroom teaching strategies, and in the case of this study, to explore the use
      of compact language drills (CLDs) as a technique for helping a deaf child improve
      his ability to use 4 irregular verbs. The CLDs were conducted 5-10 minutes each
      day for five weeks at the close of school. The drills engaged the child in
      immediate recall of simple sentences loaded with semantic/syntactic clues which
      signalled the need for a past, present or future irregular verb within the target
      sentence. The results suggest that CLDs, when used systematically, can
      significantly improve a child's ability to use irregular verbs correctly, both
      immediately following treatment, and across time.

PMID- 9002320
TI  - Breaking the silence about sexual abuse of deaf youth.
AB  - Sexual abuse of deaf youth is a serious problem that needs to have attention
      given to it in a way that will lead to real changes in the lives of the boys and
      girls affected. Through the use of an emancipatory approach to research, this
      study investigated the various theories that people hold as to why sexual abuse
      occurs in this population and what can be done to prevent it. Data were collected
      at one residential school through document review, observation, interviews, and a
      survey of staff. The results revealed that some participants held theories that
      blame the victim or the culture and that such theories would not lead to
      positive, meaningful change. Other theories that recognize the power inequities
      inherent in a sexual abuse situation are discussed as leading to potentially
      fruitful political and social actions.

PMID- 9002321
TI  - Some characteristics of mainstreamed hard of hearing students in Swedish
      Universities.
AB  - A group of 26 hard of hearing university students answered a questionnaire about
      their socioeconomic status, health, social support, well-being, and educational
      experiences. Results indicated that hard of hearing university students in Sweden
      are from families of higher socioeconomic status than their hearing peers, have a
      greater number of minor medical complaints, report more frequent feelings of
      loneliness and mild depression, are more pessimistic about the future, experience
      greater anxiety, and have slightly weaker social networks and support systems.
      However, variables related to their educational settings indicated stronger
      commitment, greater academic and classroom integration, and a less stressful
      academic experience than their hearing peers.

PMID- 9002322
TI  - Strategic planning: purpose and process in transforming state supported special
      schools for the sensory disabled in the United States.
AB  - Since the enactment of PL 94-142 the national enrollment in state special schools
      for the deaf has been reduced by more than one half; and in almost every state
      policy-makers are seriously questioning the costs of special education. These
      powerful social, political, and economic forces have impacted the special schools
      for the sensory disabled; virtually demanding that the schools examine their
      institutional future and plan accordingly. This article offers a suggested
      approach for special schools to study their purpose and the means or process by
      which they conduct their work in the education of the deaf, the blind, and the
      sensory multi-disabled. In conducting a strategic plan for a special school it
      sets a future course for the school that can transform the school from what is to
      what must be.

PMID- 9002323
TI  - The Interactive Video-Questionnaire: a new technology for interviewing deaf
      persons.
AB  - This paper traces the development of a new technology, the Interactive Video
      Questionnaire, for interviewing Deaf persons by using manually signed
      questionnaires. After encountering numerous obstacles to conducting surveys with
      Deaf persons about substance abuse using the same methods typically used with
      hearing persons, the researchers, with a Small Business Innovative Research grant
      from the National Institute on Drug Abuse, piloted a survey method that uses
      videodisc and bar code readers to present survey questions signed on screen in
      American Sign Language and Signed English. Following consultations with Deaf
      participants, deficiencies of this method were identified and corrected. An
      interactive multimedia program was created in Phase II of this research effort
      that offered questions visually in American Sign Language, Signed English, or
      Speechreading. All questions were subtitled in written English, with Touchscreen
      entry and automatic data capture and storage. The potential exists for many
      important uses of the Interactive Video-Questionnaire.

PMID- 9002324
TI  - Stereotyped behaviors in deaf and hard of hearing children.
AB  - Stereotyped behaviors frequently cause anxiety to parents and educators, and
      behaviors that appear stereotyped may prompt negative reactions. There has been
      little research on whether deaf or hard of hearing children display such
      behaviors. This study surveyed 390 students aged 3-24 years attending 3
      residential schools for the deaf and hard of hearing in the United Kingdom. At
      least 1 additional disability was reported in 79% of the students. The main
      findings were that: deaf and hard of hearing children without additional
      disabilities did not show apparently stereotyped behaviors; approximately 35% of
      children with additional disabilities did show such behaviors; some disabilities,
      in addition to hearing loss, were more likely than others to be associated with
      stereotyped behaviors. Implications of these findings for further research are
      considered with a view toward making recommendations for educational practice.

PMID- 9002325
TI  - Public health issues and clinical and neurological characteristics of the new
      variant of Creutzfeldt-Jakob disease and other human and animal transmissible
      spongiform encephalopathies: memorandum from two WHO meetings.
AB  - The transmissible spongiform encephalopathies (TSEs) include bovine spongiform
      encephalopathy (BSE), which was first described in 1986 in cattle in the United
      Kingdom, but has occurred subsequently also in other countries, and Creutzfeldt
      Jakob disease (CJD) in humans, which is rare but with a worldwide distribution.
      Recently a new variant form of CJD, with a characteristic clinical and
      pathological phenotype, has been identified in the United Kingdom in a series of
      11 young patients. This Memorandum reports the findings of two WHO Consultations.
      The first, held on 2-3 April 1996, issued conclusions and recommendations on
      certain animal products in order to protect the health of consumers. The second,
      held on 14-16 May 1996, examined, inter alia, the findings associated with the
      new variant of CJD, compared these findings with those for other TSEs, and
      proposed a protocol for the diagnosis and surveillance of CJD and related
      diseases.

PMID- 9002326
TI  - Anthrax: memorandum from a WHO meeting.
AB  - The risk of anthrax can be reduced through international collaboration in health
      education and training, promotion of research, and provision of scientific and
      technical advice. These issues were discussed by a WHO Working Group on Anthrax
      in September 1995, and this Memorandum presents their priority concerns and
      recommendations in several areas: surveillance, epidemiology, diagnosis in humans
      and in animals, prevention and control, and international cooperation.

PMID- 9002328
TI  - Evaluation of an algorithm for the treatment of persistent diarrhoea: a
      multicentre study. International Working Group on Persistent Diarrhoea.
AB  - Described are the findings of a multicentre cohort study to test an algorithm for
      the treatment of persistent diarrhoea relying on the use of locally available,
      inexpensive foods, vitamin and mineral supplementation, and the selective use of
      antibiotics to treat associated infections. The initial diet (A) contained
      cereals, vegetable oil, and animal milk or yoghurt. The diet (B) offered when the
      patient did not improve with the initial regimen was lactose free, and the energy
      from cereals was partially replaced by simple sugars. A total of 460 children
      with persistent diarrhoea, aged 4-36 months, were enrolled at study centres in
      Bangladesh, India, Mexico, Pakistan, Peru, and Viet Nam. The study population was
      young (11.5 +/- 5.7 months) and malnourished (mean weight-for-age Z-score, -3.03
      +/- 0.86), and severe associated conditions were common (45% required rehydration
      or treatment of severe infections on admission). The overall success rate of the
      treatment algorithm was 80% (95% CI, 76-84%). The recovery rate among all
      children with only diet A was 65% (95% CI, 61-70%), and was 71% (95% CI, 62-81%)
      for those evaluated after receiving diet B. The children at the greatest risk for
      treatment failure were those who had acute associated illnesses (including
      cholera, septicaemia, and urinary tract infections), required intravenous
      antibiotics, and had the highest initial purging rates. Our results indicate that
      the short-term treatment of persistent diarrhoea can be accomplished safely and
      effectively, in the majority of patients, using an algorithm relying primarily on
      locally available foods and simple clinical guidelines. This study should help
      establish rational and effective treatment for persistent diarrhoea.

PMID- 9002327
TI  - Efficacy of standard glucose-based and reduced-osmolarity maltodextrin-based oral
      rehydration solutions: effect of sugar malabsorption.
AB  - Previously we reported that standard oral rehydration salts (ORS) solution is not
      as effective as a reduced-osmolarity glucose-based ORS for the treatment of
      children with acute noncholera diarrhoea: with standard ORS the diarrhoea lasts
      longer, stool output is greater, serum sodium is higher, and there is more need
      for supplemental intravenous infusion. We studied a reduced-osmolarity
      maltodextrin (MD)-based ORS to determine whether it had similar benefits, and
      also the effect of sugar malabsorption on the efficacy of standard and MD-based
      ORS. A total of 90 boys aged 3-24 months with acute noncholera diarrhoea and
      moderate dehydration were randomly assigned to either standard ORS (glucose 20
      g/l, osmolarity 311 mmol/l) or MD-ORS (MD 50 g/l, osmolarity 227 mmol/l). There
      were no differences in treatment results. Some 46% of subjects had a high total
      stool output (> 300 g/kg), which was unrelated to the type of ORS given. High
      stool output was significantly associated with a longer duration of diarrhoea (33
      vs. 15 hours; P < 0.001), a persistently elevated serum sodium (149 vs. 144
      mmol/l at 24 h; P < 0.02), the need for intravenous infusion (11/41 vs. 0/48; P <
      0.002), and an increase in faecal reducing substances (10.8 vs. 3.4 g/l at 24 h;
      P < 0.001). We conclude that some children given standard ORS develop osmotic
      diarrhoea owing to the combined effect of transient sugar malabsorption and
      slight hypertonicity of the ORS. Earlier studies show that this adverse outcome
      can largely be avoided when extra water is given in reduced-osmolarity glucose
      based ORS. Reduced osmolarity has no benefit, however, when glucose is replaced
      by maltodextrin, probably because the sugars released by hydrolysis of MD, when
      malabsorbed, raise the intraluminal osmolarity to equal or exceed that of
      standard ORS. Thus, reduced-osmolarity glucose-based ORS is superior to both
      standard ORS and reduced-osmolarity solutions based on maltodextrin and probably
      other complex carbohydrates. Studies are in progress to define the optimal
      formulation of reduced-osmolarity glucose-based ORS.

PMID- 9002329
TI  - Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant
      rotavirus vaccine in Belem, Brazil.
AB  - A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 10(4)
      plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy
      in a prospective, randomized, double-blind, placebo-controlled trial involving
      540 Brazilian infants. Doses of vaccine or placebo were given at ages 1, 3 and 5
      months. No significant differences were noted in the occurrence of diarrhoea or
      vomiting in vaccine and placebo recipients following each dose. Low-grade fever
      occurred on days 3-5 in 2-3% of vaccinees after the first dose, but not after the
      second or third doses of vaccine. An IgA antibody response to rhesus rotavirus
      (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing
      antibody responses to individual serotypes did not exceed 20% when measured by
      fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction
      neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose
      (vaccine or placebo) recipients during two years of follow-up, 36 of them among
      children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against
      any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection
      during the first year of follow-up, when G serotype 1 rotavirus predominated, was
      57% (P = 0.008), but fell to 12% in the second year. Similar results were
      obtained when analysis was restricted to episodes in which rotavirus was the only
      identified pathogen. There was a tendency for enhanced protection by vaccine
      against illness associated with an average of 6 or more stools per day. These
      results are sufficiently encouraging to warrant further studies of this vaccine
      in developing countries using a higher dosage in an attempt to improve its
      immunogenicity and efficacy.

PMID- 9002330
TI  - Standard management of acute respiratory infections in a children's hospital in
      Pakistan: impact on antibiotic use and case fatality.
AB  - Acute respiratory infections (ARI) are a leading cause of childhood morbidity and
      mortality in Pakistan. The National ARI Control Programme was launched in 1989 in
      order to reduce the mortality attributed to pneumonia, and rationalize the use of
      drugs in the management of patients with ARI. WHO's standard ARI case management
      guidelines were adopted to achieve these objectives. The medical staff at the
      Children's Hospital, Islamabad, were trained in such management in early 1990;
      further training sessions were conducted when new staff arrived. Data on
      outpatients were obtained from special ARI abstract registers, which have been
      maintained in the outpatient department since January 1990. Details on inpatients
      who were admitted with ARI were obtained from hospital registers. During the
      period 1989-92, the use of antibiotics in the outpatient department decreased
      from 54.6% to 22.9% (P < 0.0001). The case fatality rate (CFR) in children
      admitted with ARI fell from 9.9% to 4.9% (P < 0.0001), while the overall case
      fatality rate fell from 8.7% to 6.2%. Our results from a tertiary health care
      facility show that standard ARI case management reduced both antibiotic use and
      expenditure on drugs. Although the ARI case management criteria, which are more
      sensitive than the conventional diagnostic criteria of auscultation and
      radiography, led to more admissions, we believe that this strategy contributed to
      a significant reduction in the ARI case fatality rate.

PMID- 9002331
TI  - Baseline for the evaluation of an AIDS programme using prevention indicators: a
      case study in Ethiopia.
AB  - Strategies for preventing transmission of human immunodeficiency virus (HIV)
      include ensuring that individuals have adequate knowledge of how HIV infection
      can be prevented and encouraging behaviours that decrease risk of HIV infection.
      In addition, there is evidence that early and appropriate management of other
      sexually transmitted disease is effective in reducing HIV transmission.
      Programmes and projects promoting prevention of HIV transmission should be
      evaluated periodically for their effectiveness. Between March and September 1995,
      ten prevention indicators developed by the WHO Global Programme on AIDS were used
      to establish a baseline measure for evaluating the effectiveness of the Ethiopian
      AIDS control programme. The indicators were measured using a structured
      population survey, through record review and key informants, structured
      observation and interview in health care facilities, and through a serosurvey
      among antenatal clinic attenders. The following results were found: promoting
      knowledge of preventive practices was successful; a relatively high proportion of
      young male adults had sexual risk behaviour; poor condom availability outside
      Addis Ababa, the capital; and very weak STD case management. The prevalence of
      syphilis and HIV were 8.8% and 13.6%, respectively, among pregnant women aged 15
      49 years. These results should serve as a baseline for repeat surveys to assess
      the effectiveness of HIV prevention programmes in Ethiopia.

PMID- 9002332
TI  - Maximizing immunization coverage through home visits: a controlled trial in an
      urban area of Ghana.
AB  - A strategy of home visits to maximize children's immunization coverage was
      implemented in three towns in Ghana. The strategy was tested in town 1 in a
      controlled trial where clusters of children were allocated to the intervention
      and control groups. A total of 200 mothers in the intervention group were visited
      at home by non-health workers and their children were referred to a routine under
      fives' clinic. Subsequent home visits targeted at those who failed to complete
      immunization schedules were made by nurses. After 6 months, coverage had risen
      from 60% to 85%, which was 20% higher than in the town 1 control group of 219 age
      matched children (P < 0.005). A similar home-visiting strategy in a neighbouring
      town resulted in a rise in coverage from 38% to 91% (n = 55), mainly through home
      immunizations. Children were more likely to complete the schedule if their
      fathers were interviewed and participated in the decision to send them to the
      clinic. Countries with national service programmes can use a home-visiting
      strategy to supplement and strengthen their routine immunization programmes. A
      wide range of other community-based primary health care interventions could also
      be tested and implemented using this methodology.

PMID- 9002333
TI  - A simplified screening test for identifying people with low vision in developing
      countries.
AB  - Simple but effective tests have been produced for screening subjects with low
      vision in developing countries. These tests of distance and near vision, based on
      the E test, were evaluated and validated in trials with people aged 4-90 years,
      and have been field tested in the health, education and rehabilitation services
      in 32 developing countries. Their sensitivity and specificity as screening tools
      for low vision have been calculated; sensitivity of 85% and specificity of 96%
      for the distance vision test, and sensitivity of 100% and specificity of 84% for
      the near vision test. The content and format of the tests have been demonstrated
      to be appropriate for developing countries, and their effectiveness for screening
      for low vision has been confirmed.

PMID- 9002336
TI  - A dissemination research agenda to strengthen health promotion and disease
      prevention.
AB  - The question of how to enhance the dissemination of knowledge and the use of
      innovations related to disease prevention and health promotion was posed to an
      international group of experts at an invitational research conference held in
      Vancouver, British Columbia in March 1995. The Canadian Conference on
      Dissemination Research Strengthening Health Promotion and Disease Prevention was
      co-sponsored by 15 voluntary organizations, government agencies and industries.
      It examined advances and gaps in the study of diffusion and adoption of
      preventive knowledge and practices among health professionals and the public. It
      was the first national conference of its kind devoted to dissemination research
      and dissemination of research specifically in health promotion and disease
      prevention. This paper summarizes the major issues raised in the papers presented
      at this conference. Policies and strategies for strengthening dissemination
      research and the dissemination of health promotion knowledge and practices are
      suggested.

PMID- 9002334
TI  - Impact of nutrition education and mega-dose vitamin A supplementation on the
      health of children in Nepal.
AB  - The impact on vitamin A deficiency (VAD), wasting malnutrition, and excessive
      childhood mortality of two alternative approaches-nutrition education and mega
      dose capsule distribution (6-12-month-olds: 100,000 IU; 1-5-year-olds: 200,000
      IU)-in communities in Nepal are compared. Approximately 40,000 children from 75
      locations in seven districts in two ecological settings (lowland and hills) took
      part in the study and were randomly allocated to intervention cohorts or a
      control group. At 24 months after the implementation of the project the reduction
      of risk for xerophthalmia was greater among children whose mothers were able to
      identify vitamin-A-rich foods (relative risk (RR) = 0.25; 95% confidence interval
      (CI) = 0.10-0.62) than among the children who received mega-dose capsules (RR =
      0.59; 95% CI = 0.41-0.84). The risk of mortality at 2 years was reduced for both
      the nutrition education (RR = 0.64; 95% Cl = 0.48-0.86) and capsule distribution
      (RR = 0.57; 95% CI = 0.42-0.77) cohorts. The nutrition education programme was,
      however, more expensive to deliver than the capsule distribution programme. High
      rates of participation for children in the supplementation programme were
      achieved quickly. The nutrition education messages also spread rapidly throughout
      the study population (regardless of intervention cohort assignment). Practices,
      however, were slower to change. In communities where maternal literacy was low
      and channels of communication were limited the capsule distribution programme
      appeared to be more economical. However, there are economies of scale for
      nationwide education programmes that do not exist for capsule distribution
      programmes. Although nutrition education provides economies of scale and the
      promise of long-term sustainability, a comprehensive national programme requires
      both dietary supplementation and nutrition education components.

PMID- 9002335
TI  - Child mortality in a collapsing African society.
AB  - A cohort study of mortality among under-5-year-olds was carried out in two Somali
      villages in 1987-89, a period of economic and political collapse in the rural
      parts of the country. Analysed was the relative importance of the social
      characteristics for under-5-year-old mortality against a background of
      deteriorating political and economic conditions. Mortality increased among under
      5-year-olds from 1987 (211 per 1000) to 1988 (323 per 1000) to 1989 (414 per
      1000). The mortality risk was more pronounced for boys than girls and was more so
      for infants than children aged 1-4 years. The major signs prior to death were
      respiratory infections, diarrhoeal diseases, fever/malaria and tetanus in the
      neonatal period. Over the 3-year study period mortality rates for diarrhoeal
      diseases increased significantly, while those for respiratory infections and
      diseases preventable by immunization increased more slowly. The increasing trend
      in under-5-year-old mortality was more pronounced in instances when the mother
      derived her major income from sources other than farming and in larger
      households.

PMID- 9002337
TI  - Dissemination and utilization of health promotion and disease prevention
      knowledge: theory, research and experience.
AB  - We review the theoretical and research foundations of knowledge dissemination and
      utilization. We examine first the features that describe the typical pattern of
      the spread and adoption of ideas in populations. A second level of theory
      examines the forces that explain and predict the diffusion of health promotion
      and disease prevention knowledge and innovations in two spheres, the public
      sphere and te professional sphere. A third level of theory produces models to
      guide the planning and evaluation of dissemination efforts and advocacy for
      policies to support the application of knowledge. We trace major research
      traditions through the literature of various disciplines of professions that have
      studied diffusion. We then outline some key issues related to knowledge
      dissemination and utilization in the fields of health promotion and disease
      prevention.

PMID- 9002338
TI  - Improving the fit between research and practice in health promotion: overcoming
      structural barriers.
AB  - This paper is based on the proposition that transfer of knowledge between
      researchers and practitioners concerning effective health promotion interventions
      in less than optimal. It considers how evidence concerning effectiveness in
      health promotion is established through a sequence of research studies, and how
      such evidence is applied by health promotion practitioners and policy markers in
      deciding what to do and what to found when addressing public health problems.
      There are too few rewards for researchers to pursue research with potential for
      widespread application, and to systematically develop promising interventions to
      a stage of field dissemination. Practitioners often find themselves in the
      position of tackling a public health problem where evidence of efficacy is either
      lacking, or has to be considered alongside a desire to respond to expressed
      community needs, or the need to respond to political imperative. Some of the
      major structural barriers which prevent the flow of research into practice are
      considered, and different approaches to improving the fit between research and
      practice are proposed.

PMID- 9002339
TI  - Using diffusion theory in health promotion: the case of tobacco.
AB  - Diffusion theory can profitably be applied to a range of health problems and
      interventions. This paper uses the case of tobacco to illustrate this process.
      The diffusion of innovations model refers to the spread of new ideas, techniques
      and behaviours or products throughout populations. Those who adopt at different
      phases of the process tend to differ in predictable ways, such as age, sex,
      residence, socioeconomic status and level of access to communications, each of
      which can be employed to affect the overall rate of adoption. A series of
      perspectives are employed to examine aspects of the diffusion process for tobacco
      use. Examples from the tobacco areas are used to illustrate ways in which the
      diffusion model can be applied in the field. Applications of the model for
      prevention are presented and discussed.

PMID- 9002340
TI  - Health promotion technology transfer: organizational perspectives.
AB  - This paper explores the relationship between organizational dynamics and program
      dissemination. Specifically, it is an analysis of factors affecting the directed
      diffusion of health promotion innovations which target schools and worksites as
      delivery channels. Technology transfer is the construct which is used to capture
      this notion of directed diffusion. The term is defined for the purposes of the
      paper as all strategically planned efforts to promote, influence, or accelerate
      the natural diffusion or dissemination processes. The paper has three main
      objectives: first to identify the theoretical perspectives which have influenced
      my thinking in the area of health promotion technology transfer; second, to
      describe an organizing framework for the study of health promotion technology
      transfer; and third, to recommend directions for health promotion planning
      efforts in the future and the role that research might play in that process.

PMID- 9002341
TI  - Technology-based dissemination.
AB  - Health care reform and restructuring, changes in the scope and definitions of
      'health', 'health care' and 'health research', along with a continued emphasis on
      multidisciplinary health promotion and prevention, all indicate the need for
      information dissemination, exchange and management. Technology can be a tool to
      help meet this need, as it can help us disseminate, as well as understand the
      process of dissemination. Rapid advances in, and reduced costs of technology,
      permit the integration of this tool. This paper provides a definition for
      dissemination, along with a background and rationale as to why now is the time
      and place to harness technology to assist with the dissemination process. In
      addition, it presents well-designed studies on the effective use of technology as
      an aid to dissemination. Concrete examples of innovative technology that are
      being tested are also examined. Finally, the challenge and strategies for
      technology integration are addressed.

PMID- 9002342
TI  - Positioning dissemination in public health policy.
AB  - Research should play an important role in the implementation of health policy.
      The application of research methodologies to dissemination of knowledge and
      practice is being recognized more and more as a legitimate and important
      component of the health policy agenda. The issues and priorities concerning
      health are changing rapidly in many parts of the world. In Canada, the health
      reform process is suggesting that health policy shift from a concentration on the
      current mainly curative system to one which is more balanced, with an emphasis on
      health promotion and disease prevention, targeted not only to the individual but
      to whole populations. The reform process creates significant opportunities for
      research and emphasizes the need for dissemination of research findings. We have
      much to learn about how to disseminate to the appropriate people our current
      knowledge and the knowledge which will come from new research. A key challenges
      for dissemination is to narrow the gap between what is known and what is put into
      practice. Clearly we need to develop a much greater understanding of the dynamic
      of dissemination and the barriers to it.

PMID- 9002344
TI  - The dissemination of chronic disease prevention programs: linking science and
      practice.
AB  - A strong partnership between researchers and providers is crucial to advance the
      science of dissemination and to support dissemination of effective chronic
      disease prevention programs. We reflect on our experience in three recent
      studies, (a) COMMIT, (b) a National Survey of School Smoking Prevention Programs,
      and (c) an ongoing study of Training of Providers of Smoking Prevention Programs
      to identify specific ways in which research and provider communities might
      collaborate. We propose that a national working group of researchers and
      providers be established to support (a) dissemination of programs by creating and
      continuously updating an inventory of 'tested' methods and protocols for use in
      key community intervention channels (health care offices, worksites, etc.) and
      (b) dissemination research by establishing a shared set of research priorities
      and mechanisms to stimulate researcher-provider partnership during the research
      process.

PMID- 9002345
TI  - Promoting heart health promotion.
AB  - Prevention of ischaemic heart disease is a priority for public health. Revised
      Mandatory Guidelines have resulted in substantial investment in individual
      healthy lifestyles programs and local health units have been encouraged to
      develop comprehensive heart health promotion programs. Initiatives to support
      this direction include the Heart Health Action Program, the Canadian Heart Health
      Initiative, the Ontario Heart Health Network, the Report of the Chief Medical
      Officer of Health and the Teaching Health Unit program. In spite of this, local
      health units have been slow to adopt comprehensive heart health approaches. The
      Canadian Heart Health Initiative-Ontario Project (CHHIOP) is studying the
      dissemination of community heart health programming, particularly factors
      influencing adoption by local public health departments. CHHIOP's observational
      component uses province-wide health unit and community "scans" and in-depth
      studies using qualitative methodology. CHHIOP's interventional component is
      developing a provincial linkage system.

PMID- 9002343
TI  - The case for dissemination research in health promotion and disease prevention.
AB  - The case for dissemination research stems from the major imbalance in research
      funds available for preventive medicine, relative to needs. For examples, in the
      United States in 1992 prevention research was only 0.32% of the health care
      budget and dissemination research was a small proportion of prevention research.
      The Canadian Heart Health Initiative is an excellent example of successful
      dissemination research, based on needs assessment and evaluation of widespread
      demonstration projects. Other examples include the California Tobacco Tax
      Initiative, community projects and practitioner training. Continued professional
      and public education are needed to counter the prevalent philosophy favouring
      curative medicine; such policy documents as the Victoria Declaration for Heart
      Health and the Catalonia Declaration Investing in Heart Health are steps in this
      direction. The dissemination research agenda is broad, including replication of
      success in different geographic and cultural setting. The final goal is to hasten
      technology transfer of useful health promotion methods throughout the world.

PMID- 9002346
TI  - The Canadian Heart Health Initiative: dissemination perspectives.
AB  - The Canadian Heart Health Initiative is a country-wide strategy for the
      prevention of cardiovascular disease. Initiated with a 15-year horizon, it has
      resulted in extensive networks and coalitions involving Health Canada, the 10
      provincial departments of health and over 1,000 organizations. There are five
      phases: policy development through country-wide consultations (1986-88);
      provincial heart health surveys (1986-91); research demonstration programs (1989
      97); and evaluation (1994-97). The dissemination research phase studies the
      adoption of interventions by communities and health systems. As a paradigm for
      dissemination of health policy, some key features of the Initiative are
      translation of the science base in prevention into community programs; consensual
      policy development; federal and provincial co-funding arrangements; key role
      played by the public health system; capacity building; organization and
      management model linking activities at the national, provincial and community
      levels. The methodologies and capacities developed are applicable to other health
      promotion and disease prevention areas.

PMID- 9002347
TI  - Breast cancer screening in Canada: climbing the diffusion curve.
AB  - Results of breast cancer screening studies, which point to the efficacy of
      screening mammography in the 50 to 69 year age group, have been available for
      several years. A number of initiatives are underway in Canada in an attempt to
      assure that the diffusion for this technology occurs consistently and rapidly.
      This paper outlines the initiative of the Canadian Workshop Group of Breast
      Cancer Screening, which convened in 1988, as well as other national initiatives
      in this area. In addition, it describes the experience of one screening program
      in assessing and acting upon shortcomings in screening diffusion in its own
      province. Specifically, the use of letters of invitation, community mobilization,
      and mobile service delivery are briefly outlined. This illustrates the use of
      outcome-based research and programmatic service delivery in assisting the
      diffusion effort.

PMID- 9002348
TI  - Cognition and technology in health education research.
AB  - There is an explicit relationship between knowledge generation, transmission
      (dissemination and diffusion), knowledge acquisition, and utilization. In order
      to disseminate and diffuse information for health promotion and disease
      prevention, there is an assumption that we just need to change the behaviours of
      people. This paper challenges this notion and suggests that the thinking behind
      the behaviours (cognition) also needs to be addressed for successful acquisition
      and utilization of information. Studies focusing on cognition or thought
      processes and how sociocultural factors influence or interact with cognitive
      factors is a high priority area of research. This area of research becomes more
      important if we include technology in the health care delivery system.

PMID- 9002349
TI  - Searching for the knowledge to heal: improving the links between medical research
      and the consumer.
AB  - Canadian women are increasingly interested in taking more responsibility for
      their health. Women with breast cancer find great gaps in the information and
      treatment available to them, and request more research on treatment methods,
      including more scientific analysis of alternative treatments and avenues of
      healing, as well as research aimed at prevention. These women also experience a
      clinical practices gap, in that too many practitioners are not up-to-date on
      diagnostic practices. This must be addressed in the training of new doctors and
      through the provision of more continuing education. A third gap is the
      communications gap. Doctor-patient communication must be improved, and
      practitioners should encourage greater consumer participation. However, consumers
      would have to be trained on how the medical system works and on how to
      participate actively in their own care. Improved dissemination of health care
      research and practices can help to bridge--and eventually to close--these gaps.

PMID- 9002351
TI  - Enhancing prevention in the practice of health professionals.
AB  - The National Enhancing Prevention Steering Committee is a partnership of eleven
      national health professional associations and Health Canada. Their joint mission
      reflects the view that "to ensure the health of Canadians and to ensure an
      effective health care system, all health professionals have a key role in
      assisting individuals and communities to increase control over and improve their
      health." This paper describes the development of the National Strategy for
      Enhancing Prevention in the Practice of Health Professionals and the learning
      from that five-year process.

PMID- 9002350
TI  - Dissemination research in primary care: impacting the real world of the
      practitioner.
AB  - Dissemination research in primary care should focus on getting information our
      and changing practice. Family physicians have a strong orientation toward
      prevention and are a trusted source of advice for patients but often lack an
      infrastructure to assist in prevention. Physicians provide such preventive care
      as: health enhancement, risk avoidance, risk reduction, early identification, and
      complication reduction. Within this framework important research questions are
      raised within five areas: the system of care, office organization, the
      professional, the patient, and education. Increasing the capacity for research
      should focus on the need for multi-disciplinary teams; longitudinal community
      based cohort studies; inter-provincial studies; funded multiple-partner research
      programs; practitioners organized with a regional focus; and support for
      fellowships and investigators. The success of dissemination depends on its
      respect for the context and priorities of both practitioners and the public.

PMID- 9002352
TI  - Methodological challenges in evaluation of dissemination programs.
AB  - Several authors have suggested that the purpose of evaluating programs in their
      dissemination phase is to show that the conditions necessary to produce the
      expected outcomes are implemented. The need for outcome evaluation should thus
      decrease when a program goes from the demonstration to the dissemination phase.
      Disputing such a proposition, this paper argues that: 1) the evaluation agenda
      should be broad and open in all phases of program development; 2) the need for
      outcome assessment should be present during the entire cycle of any program's
      life, and 3) there is a need to develop creative methodological approaches to
      address issues relevent to the evaluation of dissemination programs. Finally,
      eight research strategies are presented for addressing two such issues: the
      relationship between the researcher and the program and the equivocality of the
      causal inference present during the dissemination phase.

PMID- 9002353
TI  - Health communication research and health promotion.
AB  - This paper examines the relationship between health communication research and
      health promotion. In doing so, it identifies a number of research questions,
      priorities and capacity requirements pertaining to the intersection of the two
      fields. It concludes by suggesting that there is a great need in Canada to find
      support for the development of training and research programs in health
      communication research in general, and with an emphasis on health promotion in
      particular.

PMID- 9002354
TI  - Comparative analysis of clinical manifestations of autosomal dominant polycystic
      kidney disease depending on linkage to chromosome 16.
AB  - The present study concerns 63 patients with autosomal polycystic kidney disease.
      In 35 patients the disease was linked to chromosome 16, and in the remaining 28
      it was not linked to this chromosome. A comparative clinical analysis of the
      clinical manifestations of each of the forms was carried out using the objective
      criteria of age at onset of the initial clinical manifestations of ADPKD, age at
      onset of the hypertension syndrome, age at onset of the initial chronic renal
      failure and beginning of haemodialysis. The results show that the clinical
      manifestations of ADPKD in the patients with the unlinked from are milder and
      with a better prognosis.

PMID- 9002355
TI  - In vivo noninvasive study of the mechanical properties of the human skin after
      single application of topical corticosteroids.
AB  - A noninvasive in vivo suction device for measuring skin elasticity was used to
      determine the changes in skin mechanical properties 60 min. after application of
      5 commercially available topical corticosteroids as ointments and creams. 25
      healthy volunteers (20 females and 5 males, aged 16-55 years, mean age 36 years)
      were studied. The following relative parameters, independent of skin thickness,
      were calculated and compared: R2-gross, R5-net, R7-biologic elasticity and R6
      viscoelastic/elastic ratio. Corticosteroid ointments increased the purely elastic
      parameters R2, R5 (P < 0.05) and R7 as well as the parameter of viscoelasticity,
      R6 (P < 0.001). Corticosteroid creams changed the elastic parameters slightly
      increasing significantly at the same time the viscoelastic parameter, R6 (P <
      0.05). These effects of topical corticosteroid formulations are probably due to
      the stratum corneum hydration and softening of keratin which improves the
      epidermal mechanical properties. Moreover, as a result of the dermal oedema and a
      probable biochemical effect on the basic substance, the friction between the
      fibres is reduced and interstitial fluid movement through the fibrous network is
      facilitated. The noninvasive method applied can be useful for an evaluation and
      comparison of the effects of different topical preparations on the elastic and
      viscoelastic properties of human skin.

PMID- 9002356
TI  - Retrospective long-term follow-up of the triple procedure (combined keratoplasty
      and cataract surgery).
AB  - PURPOSE: Combined keratoplasty and cataract surgery has been performed at the
      University Eye Clinic in Tubingen since the nineteen-seventies. The present study
      was carried out to evaluate the long-term efficacy of this procedure. MATERIAL
      AND METHODS: Only grafts that had been followed for at least 4 years (6.5 +/-
      2.3) were included. We studied the clinical outcome and final visual acuity of 19
      patients (mean age 70 +/- 8.4 years) who had undergone "triple procedure surgery"
      on 23 eyes at the University Eye Clinic in Tubingen between 1983 and 1991.
      RESULTS: The keratoplasty was the first for 20 eyes and a regraft procedure in
      three. The mean diameter of the donor buttons was 7.31 +/- 0.4 mm, that of the
      host transplants 7.17 +/- 0.4 mm. Intra-operative complications included four vis
      a tergo reactions and one instance of bleeding in the anterior chamber. The most
      frequent postoperative complications were astigmatism (61%) and secondary
      glaucoma (4.3%). Postoperatively, six of the affected eyes required additional
      surgery. Preoperative visual acuity (0.06 +/- 0.08) improved postoperatively to
      0.4 +/- 0.26, which was statistically significant. The postoperative retinal
      vision was 0.5 +/- 0.2. CONCLUSION: The results demonstrate the long-term success
      of the triple procedure. It can be especially recommended for patients in reduced
      general health who require rapid visual rehabilitation.

PMID- 9002357
TI  - Possibilities of interventional ultrasound in diagnosing diffuse hepatic lesions-
      our modification of the classical method.
AB  - 48 ultrasound-guided biopsies of diffuse hepatic lesions were performed using a
      modification of the Chiba-22G and 23G needle and a new technique of quantified
      automatic aspiration. The modifications and the new technique increased the
      technical success and improved the diagnostic parameters of the method.

PMID- 9002358
TI  - The role of ultrasound tomography in diagnosing adrenal pathology.
AB  - The present study included 97 patients (52 female and 45 male) aged 16-52 years.
      Conventional ultrasound examination of adrenal glands was made in all cases using
      a Sonoline SL-2 ultrasound tomograph. The diagnostic results from the examination
      were compared to the results from the hormonal studies, scintigraphy, computer
      tomography, angiography, surgery and the histological diagnosis. The diagnostic
      parameters of the sonographic method were assessed on the basis of the results
      obtained. The role of the ultrasound tomography in the diagnostics of different
      adrenal diseases was determined.

PMID- 9002359
TI  - Pathogenic in vitro studies of pemphigus vulgaris. I. Experimental model of
      pemphigus vulgaris in cultures in diffusion chambers.
AB  - Normal human skin, cultivated in diffusion chambers with biological membranes in
      the presence of serum from pemphigus vulgaris patient in the culture, developed
      all microscopic signs of an acantholytic process. An experimental model of
      pemphigus was thus created for the first time in our country and proposed by the
      authors as suitable basis for further studies on the disease pathogenesis and
      treatment.

PMID- 9002360
TI  - Clinical electron microscopic correlations in patients with glomerulonephritis.
AB  - The purpose of the present study was to perform an electron microscopic
      investigation of patients with chronic glomerulonephritis and to find
      correlations between the type of glomerular disorder and the features of the
      clinical course of the disease. 26 patients--16 female and 10 male aged 17-62
      years (mean age, 34.5 years) were investigated. All patients were clinically
      diagnosed as having chronic glomerulonephritis with a disease duration ranging
      from 3 months to 2 years. The main clinical and laboratory parameters studied
      were presence of edemas, hypertension, proteinuria, hyperlipidemia, haematuria
      and renal failure confirmed by the creatinine clearance. A puncture renal biopsy
      was performed by classical methods under ultrasound guidance using a Vim
      Silverman needle. An electron microscope Philips CM-12 was used in the study. We
      found in all patients a significant correlation between the degree of proteinuria
      and the marked deformation and edema of the podocyte pedicles. In making the
      integral histological diagnosis of chronic glomerulonephritis it is necessary to
      determine more precisely the mesangial involvement and the changes in the
      membrane by means of an electron microscopic study. This will be conducive to a
      reduction in the number of mistakes in diagnosing some primary chronic
      glomerulonephrites.

PMID- 9002361
TI  - Effect of butyric short-chain fatty acids on the bioelectric and contractile
      activity of gastrointestinal smooth muscle tissues.
AB  - The present study was undertaken to investigate the effect of butyric (C4) short
      chain fatty acids on the bioelectric and contractile activity of smooth muscle
      (SM) tissues from rat and guinea-pig gastrointestinal tracts. The study was
      conducted in vitro on isolated SM preparations of rat gastric corpus and guinea
      pig taenia coli. The following methods were used: 1. Recording of bioelectric
      activity using the single sucrose gap method. 2. Isometric recording of smooth
      muscle contractility. The results showed that there was potentiation of the
      spontaneous bioelectric and contractile activities of SM preparations in the
      presence of butyrate (a salt of the butyrate short-chain fatty acid). This effect
      was accompanied by an increase of Ca(2+)-influx in the SM cells. The immediate
      cause for this process was elevation of prostaglandin F2-alpha level in the SM
      tissues. The present study suggested the following conclusions: 1. Butyric short
      chain fatty acid increases the contractility of gastrointestinal SM preparations
      of experimental animals. 2. This effect is produced by the immediate action of
      PGF2-alpha on smooth muscles where they are found to have elevated levels in the
      presence of butyrate.

PMID- 9002362
TI  - Acute renal failure in patients with multiple myeloma.
AB  - Nitrogen retention of various intensity was found in 61 patients with multiple
      myeloma. In seven (11%) of them the disturbances of the depurative renal function
      manifested as acute renal failure (ARF). The syndrome was characterised in
      etiologic, pathogenetic, clinical, therapeutic and prognostic aspects. ARF in the
      study developed on the background of a light chain proteinuria in patients with
      hypercalcemia, dehydration, radiocontrast studies, blood loss, surgical
      interventions, and severe infections. Following conservative treatment, the renal
      function normalized in one patient, a gradual transition to chronic renal failure
      was observed in five patients, and lethal outcome in one patient. The average
      survival rate after ARF was 8 months (1-13 months).

PMID- 9002363
TI  - Spontaneous rupture of an internal carotid artery aneurysm diagnosed as a
      peritonsillar abscess, a tonsillar and epipharyngeal carcinoma with metastasis.
AB  - The author observed a spontaneous rupture of an internal carotid artery aneurysm
      with initial manifestations of throat pain and subfebrillity. The condition was
      diagnosed as peritonsillar abscess. Two days later, a swelling appeared on the
      same side of the neck, which necessitated a revision of the primary diagnosis and
      acceptance of another one--a carcinoma of the palatine tonsil with metastasis. A
      third diagnosis was made on hospitalization--epipharyngeal carcinoma with
      metastasis. Physical examination disclosed an intact skin of the neck with a
      right-side tumefaction of a walnut size. The right tonsil was displaced
      anteriorly and medially. The epi- and hypopharynx were restricted. Simultaneous
      palpation of the displaced tonsil and the neck tumefaction showed that the lesion
      was single and pulsated. The pulsations were synchronous with the pulse. Contrast
      angiography showed an internal carotid artery aneurysm reaching the cranial base.
      The manifestation of the aneurysm by pains at the throat, subfebrillity, the
      displacement of the palatine tonsil and the appearance of a neck tumefaction were
      related to a spontaneous rupture. The absence of a skin lividity was most
      probably due to the barrier function of the neck fasciae concerning the
      haematoma.

PMID- 9002364
TI  - On a rare form of epilepsy in infants--Ohtahara syndrome.
AB  - We report 15 children with clinical and electroencephalographic evidence of
      Ohtahara syndrome. The onset of seizures in most of them was within the first
      week of life. The seizures were predominantly polymorphic and refractory to
      treatment with ACTH and anticonvulsants. Suppression-burst patterns were recorded
      on the EEG in all cases. The outcome in all children was grave--four died in the
      neonatal period, and three-in the infancy period. Five of the survivors evolved
      into the West syndrome and three-into the Lennox-Gastaut syndrome. It is
      concluded that early detection of Ohtahara syndrome is of essential importance
      for the prognosis of newborns and little infants with seizures.

PMID- 9002365
TI  - Studies on the frequency and clinical manifestations of epilepsy in infancy and
      early childhood.
AB  - The frequency, clinical manifestations and prognosis of epileptic seizures were
      analysed in 149 epileptic children aged up to three years. The frequency of
      epileptic seizures was found to have increased four-fold for the period of study.
      The generalised forms of epilepsy was found to have the greatest occurrence rate
      (65.8%). In infants the infantile spasms prevailed, and in children over the age
      of one year-the generalised tonic-clonic seizures. Partial seizures were observed
      in 24.1%, and mixed forms of epilepsies-in 10.1% of the cases. The prognosis of
      the children was comparatively good. Remission was achieved in 80.5% of the cases
      with primary generalised seizure, in 65% for those with partial seizures and in
      40% of the children with mixed forms of seizures. The secondary generalised forms
      had the poorest prognosis--remission was achieved here only in 13.3% of the
      cases.

PMID- 9002366
TI  - A controversial episode in the history of artificial cornea: the first use of
      poly(methyl methacrylate).
AB  - The introduction of the synthetic plastic poly(methyl methacrylate) as a material
      for artificial cornea (keratoprosthesis) is usually credited to William Stone,
      Jr. who allegedly performed the first experiments in 1947 and reported the
      results in 1953. As this plastic marked a revival in the development of
      artificial cornea, it is important to establish who was the first to use it and
      actually deserves the credit. This study demonstrates that at least three other
      ophthalmic surgeons (Wunsche in Germany, Franceschetti in Switzerland, and
      Gyorffy in Hungary) performed trials with keratoprostheses made from poly(methyl
      methacrylate) and published their results prior to Stone, Jr.

PMID- 9002367
TI  - Malaria Indian scenario.

PMID- 9002368
TI  - Pathology of malaria with special references to haematological changes in
      malaria.

PMID- 9002369
TI  - Pathogenesis of cerebral malaria.

PMID- 9002370
TI  - Immunity in malaria.

PMID- 9002372
TI  - Laboratory diagnosis of malaria.

PMID- 9002371
TI  - Malaria vaccine.
AB  - Recently it has become evident that he same candidate antigen can be shared by
      several of the parasite stages, and thus the concept of a multistage vaccine is
      becoming more and more attractive. A TDR Task Force evaluated the promise and
      stage of development of some 20 existing asexual blood stage candidate antigens
      and prepared a strategy for their development leading to clinical testing and
      field trials, Amongst these are merozoite surface protein 1 (MSP-1), Serine Rich
      Antigen (SERA), Apical Membrane Antigen (AMA-1), and Erythrocyte Binding Antigen
      (EBA). A field study conducted in Tanzanian children showed that the SPf66
      Colombian vaccine was safe, induced antibodies, and reduced the risk of
      developing clinical malaria by around 30%. This study, confirmed the potential of
      the vaccine to confer partial protection in areas of high as well as low
      intensity of transmission. Pfs25 is a leading candidate antigen for a
      transmission blocking vaccine. It is found in the ookinete stage of the parasite
      in the mosquito midgut. Gramme amounts of GMP-grade material have been produced
      and a vaccine based on the Pfs25 antigen formulated with alum should have gone
      into phase I and II clinical trials in the USA and Africa during 1995. Because
      the first malaria prototype vaccine to be tried out in people on a large scale
      has been the polymerized synthetic peptide developed by patarroye on the basis of
      the SPf66 antigen of P. faliciparum, the results are with much interest. It is
      still premature to predict the effectiveness of this vaccine globally, but its
      development will encourage further progress in a fields that has repeatedly been
      characterized by raised and then dashed drops. These various vaccines are based
      on the classical approach to vaccination, which is to raise host immunity against
      the parasite so as to reduce parasite densities or to sterilize an infection. A
      newer approach is development of antidisease vaccines which aim to alleviate
      morbidity by suppressing immunopathology in the host. Antidisease vaccines are
      based on neutralizing parasite components that induce host pathology, leaving the
      parasite itself directly unaffected. These effects would occur when each type of
      the disease is considered by it self; however, synergistic effects may be
      expected when they are used in combination. The rational for vaccines based on
      any of these stages was that immunization of various hosts with whole parasites
      of each of these stages has been able to induce protection or total transmission
      blocking immunity. Less significant but not to be discounted is the fact that
      natural malaria infections in humans have been shown to induce immunity against
      every one of these parasite stages against which vaccines are being developed, an
      exception to this are those stages that are present only in the mosquito vector
      with component molecules not presented to the human host, such as exclusively
      ookinete antigens. For several very apparent reasons a vaccine today is conceived
      of as subnit as opposed to show1 parasite vaccines, either in the form of a
      recombinant product or as synthetic peptide constructs. Genes coding for several
      antigens of P. falciparum and some of P. vivax have been seems to be common to
      many Plasmodium antigens; this is that they contain tandem repeats of
      oligopeptide sequences which often code for immunodominant epitopes. Following
      several decades of research on malaria vaccine development, the field at a glace
      may present a conflicting picture, with several achievements, and some
      disappointments and controversies. Issues facing the development of a malaria
      vaccine are complex. It is not clear how far we may yet be from achieving this
      goal. The work of the past decades has laid an extensive foundation of ralevant
      knowledge and technologies, and the goal it self remains as important as ever,
      will scientists remain committed to this objective?

PMID- 9002373
TI  - Clinical manifestations, complications and control of malaria.

PMID- 9002374
TI  - Cerebral malaria--a review of Indian scenario.

PMID- 9002375
TI  - Protean manifestations of malaria--(multi organ dysfunction syndrome).
AB  - Malaria may present with Multi System Organ Failure (MSOF) or Single System Organ
      Failure (SSOF). Thirteen cases of malaria are presented for their protean
      manifestations. Five patients presented for chronic urticaria with or without
      polyarticular arthritis, another mimicking acute rheumatic arthritis. A case of
      reactivation of pulmonary tuberculosis and the other to with apparent chloroquin
      resistant malaria who responded to combination of verapamil and chloroquin. A
      case developing Guillain Barre syndrome and another complicating into dilated
      cardiomyopathy are the rarities. All the cases are described and the pathogenesis
      is discussed in detail.

PMID- 9002376
TI  - Plasmodium falciparum malaria--a diagnostic dilemma.
AB  - A retrospective analysis of fifty cases where falciparum malaria was detected at
      autopsy, was done. Histopathological sections from all organs were taken.
      Cerebral malaria was seen in 44 cases on histology. Plugging of cerebral
      vasculature by parasitised erythrocytes (pRBC) was seen in all cases while Durck
      granulomas were seen in 5 cases. Multiple organ involvement was seen in form of
      sequestration of pRBC in all the cases. Positive peripheral smear was obtained in
      only 20 cases (antemortem). Twenty-nine patients had jaundice of which 18 had
      altered sensorium. They were clinically diagnosed as hepatic failure with or
      without hepatic encephalopathy. Fever as a symptom was seen in 19 patients. Age
      varied from 14 years to 80 years. Twenty-three patients died within 12 hours of
      admission, 12 other patients expired within a day. Only two cases survived more
      than a week. Specific antimalarial therapy was administered to 29 patients of
      which only 11 cases received quinine.

PMID- 9002377
TI  - Principles of management of drug sensitive, resistive & prophylaxis of malaria.

PMID- 9002378
TI  - Transfusion malaria.

PMID- 9002379
TI  - "Ayush -64"--a new anti malarial herbal compound.

PMID- 9002380
TI  - Milestones in the history of malaria.

PMID- 9002381
TI  - Long term survey of hepatitis C virus infection in hemodialysis units in Fukuoka,
      Japan.
AB  - To examine prevalence of hepatitis C virus (HCV) infection and liver dysfunction
      in hemodialysis units, we surveyed markers for HCV infection and serum alanine
      aminotransferase (ALT) in hemodialysis patients. 204 hemodialysis patients (111
      men and 93 women; mean age, 53 +/- 12 years) in four hemodialysis units in
      Fukuoka, Japan were investigated. All serum samples were tested for antibody to
      HCV (anti-HCV) by second-generation enzyme-linked immunosorbant assay (ELISA).
      HCV RNA was detected to identify present HCV infection in the anti-HCV-positive
      patients by polymerase chain reaction (PCR) using primers deduced from the 5'
      noncoding region. Liver dysfunction was defined as an elevated concentration of
      serum ALT (above 36 IU/liter) tested by a multiple autoanalyser. 105 patients
      (51.5 percent) were initially positive for anti-HCV, 95 (90.5 percent) of whom
      were also positive for HCV RNA. Ten became positive for anti-HCV in hemodialysis
      units during the observation, eight (80 percent) of whom had sustained HCV
      viremia. The route of transmission of HCV was not clear, but two of these
      patients had received blood transfusions. Of 95 patients with HCV viremia, 43
      (45.3 percent) had had liver dysfunction at least once. In conclusion, HCV
      infection continues to occur in hemodialysis units not through blood transfusion
      and many of them become HCV carriers. Liver dysfunction was found in about a half
      of HCV-infected hemodialysis patients during the observation.

PMID- 9002382
TI  - Hypercholesterolemia and the progression of the renal dysfunction in chronic
      renal failure patients.
AB  - The effect of hyperlipidemia on the progression of chronic renal failure was
      investigated in 104 chronic renal failure patients, aged 39.3 +/- 2.9 years. The
      follow up period was 4.1 +/- 2.9 years. The serum creatinine level was 2.1 +/-
      1.1 (mean +/- SD) mg/dl at the beginning of study and increased to 8.7 +/- 4.4
      mg/dl at the end of the study. The reciprocal serum creatinine concentration
      (1/Cr) was plotted against the observation time, and the slope was calculated.
      The absolute value of the slope was used as the progression rate of renal
      impairment. The progression rate was positively related to total cholesterol
      level or urinary protein score, while it was negatively related to total protein
      level. Without the influence of urinary protein score, the progression rate
      correlated with total cholesterol level. The result suggests that
      hypercholesterolemia may be an independent aggravating factor in the progression
      of renal dysfunction in chronic renal failure patients.

PMID- 9002383
TI  - Longitudinal change in serum cholesterol levels among isolated
      hypertriglyceridemic cases.
AB  - The present study investigated longitudinal change in serum cholesterols of
      isolated hypertriglyceridemic cases (54 males, 34 females) and age-matched
      controls (115 males, 98 females) based on a 4-year longitudinal observation. At
      the baseline, the level of triglyceride was significantly higher in
      hypertriglyceridemic cases (329 +/- 133mg/dl in males, 274 +/- 76mg/dl in
      females) than in the controls (81 +/- 18 mg/dl in males, 73 +/- 16mg/dl in
      females). Further, body mass index (BMI) was also significantly higher than that
      of the controls. There were no statistical differences in total cholesterol(TC)
      between the cases (197 +/- 23mg/dl males, 211 +/- 30mg/dl females) and the
      controls (189 +/- 19mg/dl males, 202 +/- 18mg/dl females). In
      hypertriglyceridemic cases, both TC and low density lipoprotein plus very low
      density lipoprotein cholesterols significantly increased between the baseline and
      the four years later (TC: 197 +/- 23mg/dl to 205 +/- 26mg/dl in males, p < 0.05.
      211 +/- 30mg/dl to 227 +/- 44mg/dl in females, p < 0.01), whereas no change was
      observed in the controls. The BMI of the cases and the controls were unchanged
      throughout the study period. The present study shows that isolated
      hypertriglyceridemia with normocholesterolemia proceeds to hypercholesterolemia,
      which is compatible with endogenous lipoprotein metabolism.

PMID- 9002384
TI  - Relationship between fluoride concentration in drinking water and mortality rate
      from uterine cancer in Okinawa prefecture, Japan.
AB  - The Okinawa Islands located in the southern-most part of Japan were under U.S.
      administration from 1945 to 1972. During that time, fluoride was added to the
      drinking water supplies in most regions. The relationship between fluoride
      concentration in drinking water and uterine cancer mortality rate was studied in
      20 municipalities of Okinawa and the data were analyzed using correlation and
      multivariate statistics. The main findings were as follows. (1) A significant
      positive correlation was found between fluoride concentration in drinking water
      and uterine cancer mortality in 20 municipalities (r = 0.626, p < 0.005). (2)
      Even after adjusting for the potential confounding variables, such as tap water
      diffusion rate, primary industry population ratio, income gap, stillbirth rate,
      divorce rate, this association was considerably significant. (3) Furthermore, the
      time trends in the uterine cancer mortality rate appear to be related to changes
      in water fluoridation practices.

PMID- 9002385
TI  - Choice of response scale for health measurement: comparison of 4, 5, and 7-point
      scales and visual analog scale.
AB  - To compare the feasibility of response scales with different numbers of steps for
      measuring health status, we assessed the ease of completing 4, 5, and 7-point
      scales and a visual analog scale. Four forms of the questionnaire, each of which
      consisted of the same ten questions about health status, but with a different
      type of scale among the four above mentioned, were given to 48 patients with a
      variety of conditions and diagnoses. The forms were attached together and the
      order in which they were presented was systematically varied considering
      permutations of forms. Respondents were asked to complete the forms following the
      order of the sheets. The 5-point scale form was most commonly chosen as the
      easiest to complete, and item omission was least frequent with this form. Similar
      high- reliability results in terms of Cronbach's alpha were achieved for each of
      the four forms. An additional survey among 153 patients confirmed the results of
      the first survey. The selection of the easiest scale to complete varied by sex
      (men preferred the 7-point scale), but was not affected by the conditions or
      diagnoses of the patients. The study suggests that the 5-point scale is most
      useful for measuring health status.

PMID- 9002387
TI  - An epidemiological study on diabetes mellitus in the population living in a
      methyl mercury polluted area.
AB  - The aim of this study was to determine the actual prevalence of diabetes mellitus
      and to investigate the contribution of various risk factors to the diabetes
      mellitus among the population in a methyl mercury polluted area. The study was a
      population based cross sectional mass screening survey. A case-control study was
      designed to estimate the role of various risk factors including methyl mercury
      exposure for diabetes mellitus. The study was confined to a small rural town 10
      km north of Minamata City; 1,087 persons older than 40 years were examined.
      Measurement of glucose metabolism was made on the basis of urine and
      haematological examinations. Data on risk factors were collected by
      questionnaire, and by measurement of body height and weight (obesity). The
      prevalence rate of the diabetes mellitus was 8.4% in males and 5.3% in females.
      The odds ratio of family history was significantly higher, 4.63. The odds ratio
      of residential history in a methyl mercury high polluted area was 0.58. The
      prevalence of the diabetes mellitus in this methyl mercury polluted area was not
      increased, contrary to what was expected based on the pathological findings.

PMID- 9002386
TI  - Very low incidence rates of community-acquired hepatitis C virus infection in
      company employees, long-term inpatients, and blood donors in Japan.
AB  - To assess the contemporary rate of hepatitis C virus (HCV) propagation in
      Japanese community, we conducted a sentinel study on three groups of people:
      company employees, long-term inpatients, and blood donors. A total of 3079
      company employees negative for anti-HCV were followed thereafter, and
      seroconversion to anti-HCV was found in 5 per 5786 person-years. None of them was
      positive for HCV RNA. In the group of 703 long-term inpatients (25 of whom were
      initially positive for anti-HCV) none showed seroconversion to anti-HCV per 2712
      person-years. As for 114,266 repeated blood donors who were initially antibody
      negative, 227 became anti-HCV positive later. Of these seroconverted donors, 83
      were found to have anti-HCV with titers of 2(6) or greater. HCV RNA was positive
      in only 3 of them. Thus, the incidence rates of acquired HCV viremia in these
      three groups were 0 for both company employees and long-term inpatients, and 1.78
      (95% C.I.: 0.37-5.19) per 100,000 person-years in blood donors. These results
      suggest that community-acquired HCV infection is now rare in Japan, and that even
      if it occurred it hardly leads to persistent viremia.

PMID- 9002388
TI  - Challenges to pediatric psychopharmacology.

PMID- 9002389
TI  - Effects of light therapy on neuropsychological function and mood in seasonal
      affective disorder.
AB  - To date, little attention has been paid to changes in neuropsychological function
      in seasonal affective disorders (SAD). In this study, we investigated the
      performance of 30 patients with SAD on a wide range of cognitive variables before
      and after 2 weeks of light treatment with either white or placebo red light, as
      well as later in the summertime. Performance of subjects with SAD on
      neuropsychological tests was compared with a group of 29 age- and education
      matched healthy control subjects. The most consistent deficits associated with
      SAD were on tests of cognitive failures, visual memory, and visual-construction
      skills. In contrast to specific bright light effects on psychiatric measures,
      reports of cognitive failures did not change with either light treatment. Visual
      memory and constructional deficits responded nonspecifically to treatment with
      either white or the presumed placebo red light. Surprisingly, visual memory
      deficits were seen again in the summer, at a time when mood, cognitive failures,
      and other cognitive functions appeared at normal levels. These data suggest that
      cognitive functioning is affected by SAD. In addition, light treatment may have
      differential effects on mood and cognition.

PMID- 9002390
TI  - Response-inhibition deficits in obsessive-compulsive disorder: an indicator of
      dysfunction in frontostriatal circuits.
AB  - Abnormalities in the orbital prefrontal cortex and its ventral striatal target
      fields are believed to be involved in causing obsessive and compulsive symptoms.
      Lesions to this brain circuitry result in a selective disturbance in suppressing
      responses to irrelevant stimuli. This disturbance might underlie the apparent
      inhibitory deficit suggested by the symptomatology of obsessive-compulsive
      disorder (OCD). Oculomotor tests were administered to 12 medication-free,
      nondepressed patients with OCD aged 18 to 44 y and 12 matched healthy controls to
      assess the ability to suppress responses and to execute delayed responses
      volitionally. Patients with OCD had more response-suppression failures than
      controls when peripheral visual targets were presented close to central fixation.
      No significant case-control differences were observed on the delayed-response
      task. A basic disturbance of neurobehavioral inhibition in OCD may underlie the
      repetitive behavior that characterizes the illness and be related to
      abnormalities in orbital prefrontal ventral striatal circuits.

PMID- 9002391
TI  - A single photon emission computed tomography scan study of striatal dopamine D2
      receptor binding with 123I-epidepride in patients with schizophrenia and
      controls.
AB  - The usefulness of 123I-epidepride as a single photon emission computed tomography
      (SPECT) scan D2 receptor ligand was examined in vivo in 13 medicated patients
      with schizophrenia and age- and sex-matched normal controls. To establish the
      effect of endogenous dopamine on 123I-epidepride binding, 4 of the 13 controls
      also received 20 mg D-amphetamine. The results showed that 123I-epidepride had
      high specific binding to the striatum in both patients with schizophrenia and
      normal controls. There was a trend for the total striatal binding of medicated
      patients with schizophrenia, as measured by total basal ganglia: frontal cortex
      (TBG:FC) ratios, to be less than the binding of controls (P = 0.053). This trend
      confirms previous work showing that antipsychotic medication decreases the number
      of D2 receptors available for binding to the radioligand. Interestingly, there
      was also a significant relationship between 123I-epidepride binding ratios and
      global functioning scales (Global Assessment of Functioning scale [GAF]) for
      schizophrenia (r = 0.56, P = 0.045), although there was no such relationship with
      the Brief Psychiatric Rating Scale (BPRS). In addition, our results showed that
      amphetamine-induced dopamine release did not alter 123I-epidepride binding,
      confirming the high specific binding of 123I-epidepride to the D2 receptor. We
      conclude that 123I-epidepride appears to be a very useful SPECT ligand for
      imaging the D2 receptor.

PMID- 9002392
TI  - Experimental neurotrophic factor therapy leads to cortical synaptic remodeling
      and compensates for behavioral deficits.
AB  - This brief review discusses experimental therapy with neurotrophic factors in a
      model of central nervous system (CNS) neural atrophy and synaptic loss resulting
      from unilateral cortical infarctions. It discusses the trophic factor protection
      of the cholinergic phenotype of neurons belonging to the forebrain-to-neocortex
      projection, as well as the capacity of trophic therapy to elicit synaptogenesis
      in the cerebral cortex of adult animals. Finally, it addresses the behavioral
      consequences of trophic factor-induced synaptic remodeling of the neocortex in
      this model.

PMID- 9002394
TI  - Nitric oxide synthesis inhibition attenuates haloperidol-induced
      supersensitivity.
AB  - Increased responsiveness to psychomotor stimulants can be produced by either
      chronic stimulant administration or by chronic dopamine receptor blockade. This
      study examined the role of nitric oxide in the development of neuroleptic-induced
      supersensitivity. N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME)
      administered during chronic intraperitoneal (i.p.) haloperidol treatment (0.2
      mg/kg/d for 14 d) was used to inhibit nitric oxide synthesis. Locomotor activity
      following a cocaine(i.p.) challenge injection (10 mg/kg) administered at 3 and 10
      d after cessation of haloperidol treatment demonstrated the development of
      supersensitivity. Haloperidol animals pretreated with L-NAME i.p. (30 mg/kg)
      showed significantly less cocaine-stimulated locomotor activity on both tests
      than saline-pretreated animals. This finding suggests that nitric oxide is
      involved in haloperidol-induced supersensitivity and that a common neural
      mechanism may underlie the development of supersensitivity and stimulant-induced
      sensitization. This study also suggests that treatment with a nitric oxide
      synthesis inhibitor may decrease the side effects accompanying long-term
      treatment with antipsychotic medications.

PMID- 9002393
TI  - Clinical features of schizophrenia in a woman with hyperandrogenism.
AB  - Ample evidence supports sex differences in the clinical features of
      schizophrenia. In this regard, estrogen may contribute to later onset and less
      severe course of illness in women. Direct investigation of hormonal status in
      schizophrenia is extremely difficult. The present report documents the clinical
      features of schizophrenia in a young woman with long-standing hyperandrogenism
      related to polycystic ovarian disease. We postulate that hyperandrogenism
      contributed to a relatively early onset, olfactory dysfunction, and other
      clinical features of schizophrenia more commonly associated with men.
      Additionally, acute estrogen depletion following cessation of oral contraceptives
      may have precipitated psychosis, while recommencement of oral contraceptives
      could have contributed to subsequent improvement in symptoms.

PMID- 9002396
TI  - Privacy at risk. Whose? Yours!

PMID- 9002395
TI  - Pemoline augmentation for resistant depression.

PMID- 9002397
TI  - Some general observations.

PMID- 9002398
TI  - Treating halitosis.

PMID- 9002399
TI  - Gold restorations.

PMID- 9002400
TI  - An evaluation of casting alloys used for restorative procedures.
AB  - Dental casting alloys have played a major role in the restorative process for
      three-quarters of a century. Gold-based compositions were used almost exclusively
      for most of that time-but because of their relatively high cost, they began to be
      replaced by a number of base metal alloys. This article discusses some of the
      most recent findings about the composition of alloy systems and the possible
      tissue responses to those systems.

PMID- 9002401
TI  - Grinding precision and accuracy of fit of CEREC 2 CAD-CIM inlays.
AB  - The authors conducted research to determine the grinding precision and accuracy
      of fit of ceramic inlays generated with the completely redesigned CEREC 2
      computer-assisted design/computer-integrated manufacturing, or CAD-CIM, unit.
      They found that the grinding precision of the CEREC 2 unit was 2.4 times greater
      than that of CEREC 1. With CEREC 2, the mean (+/-standard deviation) luting
      interfaces were 56 +/- 27 micrometers, which is a 30 percent improvement in the
      accuracy of fit compared with that of CEREC 1.

PMID- 9002402
TI  - Reducing the risk of needlesticks: methods used to reload syringes.
AB  - To achieve local anesthesia, dentists may need to administer a second injection.
      One widely used textbook advocates removing the needle before replacing the used
      cartridge. To determine the extent to which practicing dentists follow this
      recommendation, the author surveyed 144 practicing dentists in an upstate New
      York community and found that only 3 percent use this method. The rest leave the
      needle on to minimize their risk of a needlestick.

PMID- 9002403
TI  - Medical considerations for dental care of patients with alcohol-related liver
      disease.
AB  - More than 7 percent of all adults in the United States have met diagnostic
      criteria for alcohol abuse and alcohol dependence. Many of these people and even
      occasional users of alcohol may exhibit medical complexities, particularly liver
      disease, that can adversely affect provision of routine dental care. This article
      highlights some of the important clinical topics associated with alcoholic liver
      disease as it relates to dental care and provides guidelines on treatment of
      affected people.

PMID- 9002404
TI  - Evidence-based care of musculoskeletal facial pain: implications for the clinical
      science of dentistry.
AB  - The authors assert that advancement of dentistry as a clinical science has been
      hampered by a failure to practice evidence-based care, which incorporates
      principles derived from clinical epidemiology. The schism between the cultures of
      researcher and practitioner was most evident at a recent National Institutes of
      Health Technology Assessment Conference on the Management of Temporomandibular
      Disorders.

PMID- 9002405
TI  - The diagnosis and treatment of central giant cell granuloma.
AB  - This report reviews the literature involving the central giant cell granuloma.
      Diagnosis and treatment is presented. The article reports the case of a child who
      was initially seen in her general dentist's office, then referred to an oral and
      maxillofacial surgeon. Differential diagnoses of both benign and malignant
      lesions related to the central giant cell tumor are discussed.

PMID- 9002406
TI  - Dental surgery and the general practitioner.

PMID- 9002407
TI  - Computer use by dentists and dental team members.
AB  - Since 1984, the ADA Survey Center has collected data on the use of computers in
      dental offices. This article presents some of these data, which indicate that the
      computerized dental practice has become an industry standard.

PMID- 9002408
TI  - Effective orthodontics: achieving objectives, avoiding misadventures.
AB  - The authors outline four principles that should be considered when planning
      orthodontic tooth movement. They suggest that dentists have clear treatment
      objectives, know the force requirements to achieve those objectives, choose the
      best equipment to provide the needed forces and prevent unwanted tooth movement
      during treatment. To illustrate use of these principles, the authors refer to a
      sample treatment scenario. They also provide a mnemonic device to help dentists
      recall these principles.

PMID- 9002409
TI  - Emerging and re-emerging infectious diseases: a biological evolutionary drama.

PMID- 9002410
TI  - Power of attorney.

PMID- 9002412
TI  - HIV/AIDS in African Americans: role of the National Medical Association in
      diagnosis, treatment, and eradication.

PMID- 9002411
TI  - Decision making in colorectal cancer screening.

PMID- 9002413
TI  - Cancer risk assessment.
AB  - Increasing efforts to reduce the burden of cancer have brought into sharp relief
      the relevance of cancer risk assessment in preventing the occurrence and, when
      that is not possible, preventing the progression of the disease. Methods for
      estimating human cancer risk have evolved steadily over the past few decades as
      more has been learned about molecular, genetic, and biological aspects of cancer.
      These methods have been applied with increasing frequency in community-based
      approaches to reduce the risk of environmentally provoked cancers. At the same
      time, patients are showing increased interest in estimates of their likelihood of
      developing cancer during the next 10, 20, or 30 years. This interest is involving
      more physicians in human cancer risk assessment in clinical counseling settings.

PMID- 9002414
TI  - Early life experiences linked to diabetes mellitus: a study of African-American
      migration.
AB  - African Americans experienced massive internal migrations that shifted more than
      6 million Southern-born blacks to other sections of the United States over the
      past century, a trend that only recently has been reversed. Whenever mass
      migration takes place, there is an opportunity to examine the role of the native
      and relocated environments in the development of disease. This article examines
      those relationships for diabetes mellitus, a group of diseases that
      disproportionately affect African-Americans relative to other racial and ethnic
      groups in the United States. Age-specific and age-adjusted rates with 95%
      confidence intervals were calculated for males and females for combinations of
      five regions of birth and four regions of residence at time of death. Southern
      born males had statistically significantly higher death rates from diabetes than
      did their counterparts who died in the same regions in 9 of 16 comparisons. For
      females, those born in the South had statistically significantly higher rates in
      15 of 16 comparisons. The results of this study indicate that place of birth and
      early life experiences are statistically associated with diabetes mortality among
      African Americans regardless of place of residence at time of death.

PMID- 9002416
TI  - Growth of trypanosomes in vivo, host body weight gains, and food consumption in
      zinc-deficient mice.
AB  - This study examined the effect of zinc deficiency on food consumption and the
      growth of mice infected with Trypanosoma musculi or immunized with parasite
      products. In addition, the effects of zinc deficiency on the growth and
      development of parasites in vivo was studied. Infected mice consumed more food
      than noninfected mice, and the level of food consumption in the zinc-deficient
      mice was much less and showed general decline during the observation period.
      Also, infected mice on both full-complement and zinc-deficient diets gained more
      body weight than control mice. Throughout the observational period, trypanosomes
      from zinc-deficient mice showed considerably higher variability in size as
      determined by coefficient of variation. In both dietary groups, the average
      length of trypanosomes was not significantly different.

PMID- 9002418
TI  - Black African neurosurgeons practicing on the African continent.

PMID- 9002417
TI  - Correlation between self-reported cocaine use and urine toxicology in an inner
      city prenatal population.
AB  - To determine the prevalence of recent cocaine use and the accuracy of self
      reported use, the results of a urine assay for the major cocaine metabolite
      benzoylecgonine were compared with self-reported cocaine use in an inner-city
      prenatal population offered routine voluntary urine toxicology screening at the
      time of registration for prenatal care. During a 1-year period, 6866 women
      registered for prenatal care and 5200 (76%) consented to urine assays for cocaine
      metabolites. Of the women consenting to urine assays, 253 (5%) had positive
      assays for benzoylecgonine. Women with positive assays were significantly more
      likely than those with negative assays to be older (mean [SD] 27 [5] versus 23
      [6] years), black, single, and unemployed. In addition, women with positive
      assays were significantly more likely to be multiparous, report > two sexual
      partners in the previous year, and acknowledge a history of a sexually
      transmitted disease (STD). Forty-seven percent of women with positive assays
      acknowledged cocaine use in the 6 months prior to sampling. Women with positive
      assays who denied cocaine use were significantly more likely than those who
      admitted use to be younger (mean [SD] 26 [5] versus 28 [4] years), to report > or
      = two sexual partners in the past year, and acknowledge a history of an STD. This
      analysis revealed a poor correlation between self-reported cocaine use and the
      results of urine assays for cocaine metabolites among women seeking prenatal care
      in an inner-city institution.

PMID- 9002415
TI  - Coronary heart disease risk factors and cigarette smoking among rural African
      Americans.
AB  - Cigarette smoking has been reported to worsen high-density lipoprotein (HDL)
      cholesterol and other cardiac risk factors, yet no studies have examined this
      issue among rural African Americans. This study examines the association between
      cigarette smoking and cardiac risk factors among rural African Americans. A
      population-based sample of 403 African-American adults from two rural Virginia
      counties underwent total cholesterol (TC), HDL, systolic and diastolic blood
      pressure (SBP and DBP), body mass index (BMI), serum glucose, and glycosylated
      hemoglobin (GlyHb) measurements. Cross-sectional multivariate analyses were used
      to compare risk factors across categories of cigarette use. Age, BMI, alcohol
      consumption, and the use of antihypertensive medications were covariates in the
      analysis. Results indicated that female light smokers had significantly lower SBP
      and DBP, and lower HDL. Female heavy smokers had significantly lower HDL and BMI
      and significantly higher TC/HDL ratios. Male heavy smokers had significantly
      higher SBP. More than 33% of males and more than 50% of females were overweight,
      and increasing BMI was associated with significantly or nearly significantly
      worsening of all other risk factor levels. Both cigarette smoking and obesity
      adversely affect other cardiac risk factors. Novel approaches are needed to
      decrease both smoking and obesity in this difficult to reach population.

PMID- 9002419
TI  - Bilateral rudimentary first ribs as a cause of thoracic outlet syndrome.
AB  - First rib abnormalities are an uncommon cause of thoracic outlet syndrome.
      Cervical ribs are a much more frequent source of thoracic outlet syndrome, and in
      more than 95% of these patients, the symptoms are neurologic, not vascular.
      Rudimentary first ribs, however, uncommonly produce exclusively neurologic
      symptoms and usually manifest with vascular pathology. This article reviews a
      case of a patient with bilateral extensively neurologic thoracic outlet syndrome
      symptoms arising from bilateral rudimentary first ribs. The symptoms, pathologic
      features, and treatment, as well as an algorithm for working up patients with
      thoracic outlet syndrome, are discussed. Bilateral transaxillary first rib
      resection was curative in this patient and is the treatment of choice for either
      neurologic or vascular manifestations of thoracic outlet syndrome associated with
      rudimentary first ribs.

PMID- 9002420
TI  - Transmitter modulation of neuronal calcium channels.

PMID- 9002422
TI  - Ion channel phenotype of melanoma cell lines.
AB  - Melanoma cells are transformed melanocytes of neural crest origin. K+ channel
      blockers have been reported to inhibit melanoma cell proliferation. We used whole
      cell recording to characterize ion channels in four different human melanoma cell
      lines (C8161, C832C, C8146, and SK28). Protocols were used to identify voltage
      gated (KV), Ca2+-activated (KCa), and inwardly rectifying (KIR) K+ channels;
      swelling-sensitive Cl- channels (Clswell); voltage-gated Ca2+ channels (CaV) and
      Ca2+ channels activated by depletion of intracellular Ca2+ stores (CRAC); and
      voltage-gated Na+ channels (NaV). The presence of Ca2+ channels activated by
      intracellular store depletion was further tested using thapsigargin to elicit a
      rise in [Ca2+]i. The expression of K+ channels varied widely between different
      cell lines and was also influenced by culture conditions. KIR channels were found
      in all cell lines, but with varying abundance. Whole-cell conductance levels for
      KIR differed between C8161 (100 pS/pF) and SK28 (360 pS/pF). KCa channels in
      C8161 cells were blocked by 10 nm apamin, but were unaffected by charybdotoxin
      (CTX). KCa channels in C8146 and SK28 cells were sensitive to CTX (Kd = 4 nm),
      but were unaffected by apamin. KV channels, found only in C8146 cells, activated
      at approximately -20 mV and showed use dependence. All melanoma lines tested
      expressed CRAC channels and a novel Clswell channel. Clswell current developed at
      30 pS/sec when the cells were bathed in 80% Ringer solution, and was strongly
      outwardly rectifying (4:1 in symmetrical Cl-). We conclude that different
      melanoma cell lines express a diversity of ion channel types.

PMID- 9002421
TI  - Cysteine mapping in the ion selectivity and toxin binding region of the cardiac
      Na+ channel pore.
AB  - Aqueous exposure of critical residues in the selectivity region of voltage gated
      Na+ channels was studied by cysteine-scanning mutagenesis at three positions in
      each of the SS2 segments of domains III (D3) and IV (D4) of the human heart Na+
      channel. Ionic currents were modified by charged cysteine-specific
      methanethiosulfonate (MTS) reagents, (2-aminoethyl)methanethiosulfonate (MTSEA+)
      and (2-sulfonatoethyl)methanethiosulfonate (MTSES-) in all six of the Cys
      substituted channels, including Trp --> Cys substitutions at homologous positions
      in D3 and D4 that were predicted in secondary structure models to have buried
      side chains. Furthermore, in the absence of MTS modification, each of the Cys
      mutants showed a reduction in tetrodotoxin (TTX) block by a factor >10(2).
      Cysteine substitution without MTS modification abolished the alkali metal ion
      selectivity in K1418C (D3), but not in A1720C (the corresponding position in D4)
      suggesting that the lysine but not the alanine side chains contribute to
      selectivity even though both were exposed. Neither position responded to MTSES-
      suggesting that these residues occupy either a size- or charge-restricted region
      of the pore. By contrast, MTSES- markedly increased, and MTSEA+ markedly
      decreased conductance of D1713C (D4) suggesting that the acidic side chain of
      Asp1713 acts electrostatically in an unrestricted region. These results suggest
      that Lys1418 lies in a restricted region favorable to cations, whereas Asp1713 is
      at a more peripheral location in the Na+ channel pore.

PMID- 9002423
TI  - Hyperpolarization-activated Ca2+-permeable channels in the plasma membrane of
      tomato cells.
AB  - The hyperpolarization of the electrical plasma membrane potential difference has
      been identified as an early response of plant cells to various signals including
      fungal elicitors. The hyperpolarization-activated influx of Ca2+ into tomato
      cells was examined by the application of conventional patch clamp techniques. In
      both whole cell and single-channel recordings, clamped membrane voltages more
      negative than -120 mV resulted in time- and voltage-dependent current activation.
      Single-channel currents saturated with increasing activities of Ca2+ and Ba2+
      from 3 to 26 mm and the single channel conductance increased from 4 pS to 11 pS
      in the presence of 20 mm Ca2+ or Ba2+, respectively. These channels were 20-25
      and 10-13 times more permeable to Ca2+ than to K+ and to Cl-, respectively.
      Channel currents were strongly inhibited by 10 microM lanthanum and 50% inhibited
      by 100 microM nifedipine. This evidence suggests that hyperpolarization-activated
      Ca2+-permeable channels provide a mechanism for the influx of Ca2+ into tomato
      cells.

PMID- 9002424
TI  - Evidence that calcium release-activated current mediates the biphasic electrical
      activity of mouse pancreatic beta-cells.
AB  - The electrical response of pancreatic beta-cells to step increases in glucose
      concentration is biphasic, consisting of a prolonged depolarization with action
      potentials (Phase 1) followed by membrane potential oscillations known as bursts.
      We have proposed that the Phase 1 response results from the combined depolarizing
      influences of potassium channel closure and an inward, nonselective cation
      current (ICRAN) that activates as intracellular calcium stores empty during
      exposure to basal glucose (Bertram et al., 1995). The stores refill during Phase
      1, deactivating ICRAN and allowing steady-state bursting to commence. We support
      this hypothesis with additional simulations and experimental results indicating
      that Phase 1 duration is sensitive to the filling state of intracellular calcium
      stores. First, the duration of the Phase 1 transient increases with duration of
      prior exposure to basal (2.8 mM) glucose, reflecting the increased time required
      to fill calcium stores that have been emptying for longer periods. Second, Phase
      1 duration is reduced when islets are exposed to elevated K+ to refill calcium
      stores in the presence of basal glucose. Third, when extracellular calcium is
      removed during the basal glucose exposure to reduce calcium influx into the
      stores, Phase 1 duration increases. Finally, no Phase 1 is observed following
      hyperpolarization of the beta-cell membrane with diazoxide in the continued
      presence of 11 mm glucose, a condition in which intracellular calcium stores
      remain full. Application of carbachol to empty calcium stores during basal
      glucose exposure did not increase Phase 1 duration as the model predicts. Despite
      this discrepancy, the good agreement between most of the experimental results and
      the model predictions provides evidence that a calcium release-activated current
      mediates the Phase 1 electrical response of the pancreatic beta-cell.

PMID- 9002425
TI  - Leukotriene D4-induced Ca2+ mobilization in Ehrlich ascites tumor cells.
AB  - Stimulation of Ehrlich ascites tumor cells with leukotriene D4 (LTD4) within the
      concentration range 1-100 nm leads to a concentration-dependent, transient
      increase in the intracellular, free Ca2+ concentration, [Ca2+]i. The Ca2+ peak
      time, i.e., the time between addition of LTD4 and the highest measured [Ca2+]i
      value, is in the range 0.20 to 0.21 min in ten out of fourteen independent
      experiments. After addition of a saturating concentration of LTD4 (100 nm), the
      highest measured increase in [Ca2+]i in Ehrlich cells suspended in Ca2+
      containing medium is 260 +/- 14 nm and the EC50 value for LTD4-induced Ca2+
      mobilization is estimated at 10 nM. Neither the peptido-leukotrienes LTC4 and
      LTE4 nor LTB4 are able to mimic or block the LTD4-induced Ca2+ mobilization,
      hence the receptor is specific for LTD4. Removal of Ca2+ from the experimental
      buffer significantly reduces the size of the LTD4-induced increase in [Ca2+]i.
      Furthermore, depletion of the intracellular Ins(1,4,5)P3-sensitive Ca2+ stores by
      addition of the ER-Ca2+-ATPase inhibitor thapsigargin also reduces the size of
      the LTD4-induced increase in [Ca2+]i in Ehrlich cells suspended in Ca2+
      containing medium, and completely abolishes the LTD4-induced increase in [Ca2+]i
      in Ehrlich cells suspended in Ca2+-free medium containing EGTA. Thus, the LTD4
      induced increase in [Ca2+]i in Ehrlich cells involves an influx of Ca2+ from the
      extracellular compartment as well as a release of Ca2+ from intracellular
      Ins(1,4,5)P3-sensitive stores. The Ca2+ peak times for the LTD4-induced Ca2+
      influx and for the LTD4-induced Ca2+ release are recorded in the time range 0.20
      to 0.21 min in four out of five experiments and in the time range 0.34 to 0.35
      min in six out of eight experiments, respectively. Stimulation with LTD4 also
      induces a transient increase in Ins(1,4, 5)P3 generation in the Ehrlich cells,
      and the Ins(1,4,5)P3 peak time is recorded in the time range 0.27 to 0.30 min.
      Thus, the Ins(1,4, 5)P3 content seems to increase before the LTD4-induced Ca2+
      release from the intracellular stores but after the LTD4-induced Ca2+ influx.
      Inhibition of phospholipase C by preincubation with U73122 abolishes the LTD4
      induced increase in Ins(1,4,5)P3 as well as the LTD4-induced increase in [Ca2+]i,
      indicating that a U73122-sensitivity phospholipase C is involved in the LTD4
      induced Ca2+ mobilization in Ehrlich cells. The LTD4-induced Ca2+ influx is
      insensitive to verapamil, gadolinium and SK&F 96365, suggesting that the LTD4
      activated Ca2+ channel in Ehrlich cells is neither voltage gated nor stretch
      activated and most probably not receptor operated. In conclusion, LTD4 acts in
      the Ehrlich cells via a specific receptor for LTD4, which upon stimulation
      initiates an influx of Ca2+, through yet unidentified Ca2+ channels, and an
      activation of a U73122-sensitive phospholipase C, Ins(1,4,5)P3 formation and
      finally release of Ca2+ from the intracellular Ins(1,4,5)P3-sensitive stores.

PMID- 9002426
TI  - Dual role of prostaglandins (PGE2) in regulation of channel density and open
      probability of epithelial Na+ channels in frog skin (R. pipiens).
AB  - Prostaglandins are important in signaling pathways involved in modulating the
      rates of Na+ transport in a diverse group of tissues possessing apical membrane
      epithelial channels. PGE2 is known to cause either stimulation, inhibition or
      transient stimulatory changes of Na+ transport. We have continued our studies of
      frog skins that are known to respond to forskolin and PGE2 with large steady
      state increases of transport and have used noninvasive methods of blocker-induced
      noise analysis of Na+ channels to determine their channel densities (NT) and open
      probabilities (Po). In the absence of exogenous hormones, baseline rates of Na+
      transport are especially high in scraped skins (R. pipiens pipiens) studied in
      the fall of the year. Na+ transport was inhibited by indomethacin and by removal
      of the unstirred layers of the corium (isolated epithelia) alone suggesting that
      PGE2 is responsible for the sustained and elevated rates of transport in scraped
      skins. Changes of transport caused by indomethacin, forskolin or PGE2 were
      unquestionably mediated by considerably larger changes of NT than compensatory
      changes of Po. Since cAMP caused no change of Po in tissues pretreated with
      indomethacin, PGE2 appears in this tissue to serve a dual role, increasing the
      steady state NT by way of cAMP and decreasing Po by unknown mechanisms. Despite
      appreciable PGE2-related decreases of Po, the net stimulation of transport occurs
      by a considerably greater cAMP-mediated increase of NT.

PMID- 9002427
TI  - Fusion of human sperm to prostasomes at acidic pH.
AB  - Prostasomes are membranous vesicles (150-200 nm diameter) present in human semen.
      They are secreted by the prostate and contain large amounts of cholesterol,
      sphingomyelin and Ca2+. In addition, some of their proteins are enzymes.
      Prostasomes enhance the motility of ejaculated spermatozoa and are involved in a
      number of additional biological functions. The possibility that they may fuse to
      sperm has never been proved. In this work, we studied the fusion of sperm to
      prostasomes by using various methods (relief of octadecyl Rhodamine B
      fluorescence self-quenching, fluorescence microscopy and flow cytometry) and we
      found that it occurs at acidic pH (4-5), but not at pH 7.5 pH-dependent fusion
      relies on the integrity of one or more proteins and is different from the Ca2+
      stimulated fusion between rat liver liposomes and spermatozoa that does not
      require any protein and occurs at neutral pH. We think that the H+-dependent
      fusion of prostasomes to sperm may have physiological importance by modifying the
      lipid and protein pattern of sperm membranes.

PMID- 9002428
TI  - The Ca2+-inactivated Cl- channel at work: selectivity, blocker kinetics and
      transport visualization.
AB  - Removal of extracellular divalent cations activated a Cl- channel in the plasma
      membrane of Xenopus laevis oocytes. This so-called Ca2+-inactivated Cl- channel
      (CaIC) was present in every oocyte and was investigated using two-electrode whole
      cell voltage clamp and single-channel patch-clamp techniques. Beside other Cl-
      channel inhibitors, anthracene-9-carboxylic acid (9-AC) and 3' azido
      3'deoxythymidine (AZT), a nucleoside analog we used as an antiviral drug, blocked
      at least partly the CalC-mediated currents. Using the Cl--sensitive dye 6-methoxy
      N-(sulfopropyl)quinolinium (SPQ) we could visualize the transport of Cl- from the
      oocyte cytoplasm to the surrounding medium after activation of the CaIC by Ca2+
      removal. In the absence of external Cl- and Ca2+, the emission intensity of SPQ
      declined continuously, indicating a quenching of fluorescence by the efflux of Cl
      in the millimolar range. In the presence of external Ca2+, no emission changes
      could be observed during the same time period. Chelating external Ca2+ in absence
      of Cl- immediately activated Ca2+-inactivated Cl- channels leading to subsequent
      emission decrease of SPQ. Investigations on the selectivity of the CaIC revealed
      only poor discrimination between different anions. With single-channel
      measurements, we found an anion selectivity sequence I- > Br- > Cl- >> gluconate
      as it is also typical for maxi Cl- channels. Contrary to the majority of all
      other transport systems of the Xenopus oocyte, which show reduced activity due to
      membrane depolarization or endocytotic removal of the transport protein from the
      plasma membrane during oocyte maturation, the CaIC remained active in maturated
      oocytes. Single-channel measurements on maturated oocytes, also known as eggs,
      showed the presence of Ca2+-inactivated Cl- channels. However, this egg CaIC
      revealed an altered sensitivity to external Ca2+ concentrations. All these data
      confirm and extend our previous observations on the CaIC and give clear evidence
      that this channel is peculiar among all Cl- channels described up to now.

PMID- 9002429
TI  - Ecotoxicology for risk assessment in arid zones: some key issues.
AB  - In the hot arid zones of the world, ecotoxicological research is in statu
      nascendi. In these zones, the major sources of contamination by toxicants are:
      (1) plant protection and vector control in wet zones; (2) large-scale crop
      protection campaigns in dry and ephemeral wet zones; (3) refuse and obsolete
      pesticides in dry zones; and (4) mining. Economic development in many of these
      zones requires an adequate knowledge of certain basic principles, i.e., where
      extrapolating existing knowledge does not apply. The vulnerability of ecosystems
      to contaminants is closely related to water flow. In dry areas, species are
      susceptible to factors that interfere with the ecophysiological properties
      regulating water loss. Most hot arid areas are found at low latitudes where
      temperatures show striking extremes both in time and space. Living organisms are
      physiologically resistant and/or show adaptive behavior to these temperature
      extremes. Very little is known about the effects of toxicants on these key
      resistant and adaptive functions, although by extrapolation a few assumptions can
      be made. The effects of hyperthermia, for instance, can be aggravated by GSH
      depleting substances, and the temporary disabling effects characteristic of many
      pesticides may prove fatal under these circumstances. Most wet areas show a
      spatial concentration of both human activity and wildlife. In mesic zones, the
      contamination of water represents a health risk to both humans and other living
      organisms. The vast majority of aquatic communities are those inhabiting
      temporary pools and streams. Their populations are characterized by short
      reproductive cycles and/or long dormant stages. Toxicants affecting growth in
      these areas have been shown to have a deleterious effect. In a synthesis of
      existing knowledge the most prominent gaps are identified and priorities for
      further research are made.

PMID- 9002430
TI  - Community structure and dynamics in desert ecosystems: potential implications for
      insecticide risk assessment.
AB  - Insecticides are increasingly being used in hot arid ecosystems. The evaluation
      of the ecological risk these insecticides may pose, however, is based largely on
      data derived from temperate organisms and ecosystems. The major differences in
      the composition, structure, and functioning of desert animal communities when
      compared to temperate terrestrial ecosystems are discussed. Desert communities
      are characterized by a high fraction of ectotherms (both vertebrates and
      invertebrates);rodents and insectivores appear to dominate the mammalian fauna;
      and detritivores make up a very large part of the arthropod fauna. Presently
      available toxicity data cover these groups only to a very limited extent. It is
      not known if the ranges of insecticide susceptibility observed in temperate
      species are representative of those in arid organisms. Thus, it is not certain
      that ecotoxicological assessments based on such data sets adequately protect
      desert animal communities. It is shown that food web connectance is higher in
      desert ecosystems than in temperate grasslands or forests. This may to a large
      extent be due to the high degree of omnivory among desert organisms. Population
      regulation between predators and prey appears to be weaker in deserts. The same
      is often, though not always, the case for competition among desert organisms. It
      is argued that such characteristics will reduce the chance that strong indirect
      effects of insecticide perturbations will occur. In spite of the fact that many
      desert organisms are well adapted to cope with high temporal and spatial
      environmental variability, there is no reason to believe that they will always
      recover more rapidly from population perturbations caused by insecticides. The
      relatively large physiological and life-history plasticity encountered in many
      desert animals may increase tolerance to insecticide stress. Food chains are
      longer in deserts than in temperate grasslands and forests. The implications of
      this observation for the risk of biomagnification of contaminants are discussed.

PMID- 9002431
TI  - The calibration of an artificial stream system used to investigate the tolerances
      of South African riverine invertebrates to selected water quality variables.
AB  - Water quality management in South Africa aims at the maintenance of water in a
      state that is "fit for use." This includes use for agriculture, industry,
      domestic supply, and recreation,together with the maintenance of the natural,
      functioning resource base:aquatic ecosystems. The water quality requirements of
      riverine ecosystems need to be established to fulfil this last aim. A first step
      is the investigation of the tolerances of a range of riverine organisms to key
      water quality variables or pollutants. However, riverine organisms require
      flowing water, and in order to provide a flowing water experimental facility, an
      artificial stream laboratory has been developed. The objective of calibrating
      this system was to establish the physical and chemical conditions in the streams
      before test organisms were introduced; then to monitor behavior of organisms in
      the streams before water quality conditions were experimentally altered. This
      paper introduces the concept of system calibration and reports on hydraulic and
      water quality calibration, and the effects of handling on test organisms.

PMID- 9002432
TI  - Salinity tolerances of selected macroinvertebrates of the Sabie River, Kruger
      National Park, South Africa.
AB  - Salinization has been identified as the most important problem facing the
      managers of South African freshwaters. Laboratory-based toxicity tests were
      conducted to assess the tolerance of selected macroinvertebrates to elevated salt
      concentrations. Since the Kruger National Park is the focus of river research in
      South Africa, and the Sabie River is the least mineralized river in the park, 96
      h acute toxicity tests were conducted using Sabie River water and an
      ephemeropteran mayfly Tricorythus sp. found in the river. Experiments were
      conducted inflowing water systems known as raceways. The tolerance of the mayfly
      to two sodium salts, sodium chloride and sodium sulphate, was assessed at a range
      of selected conductivity levels/concentrations. The results indicated that
      mortality cannot be linked only to conductivity or total dissolved solid(TDS)
      concentrations, but also to the nature of the salt. Sodium sulphate was
      considerably more toxic to Tricorythus sp. than sodium chloride. Causes of
      mortality and implications for the development of water quality guidelines for
      the natural aquatic environment are discussed.

PMID- 9002433
TI  - Risk assessment as a management tool used to assess the effect of pesticide use
      in an irrigation system, situated in a semi-desert region.
AB  - A preliminary study undertaken by the CSIR in July 1993 on the health effects of
      aerial crop spraying of pesticides in the Vaalharts irrigation area in South
      Africa indicated that potential health risks could exist for the inhabitants of
      this area. An extensive scientific health risk assessment and epidemiological
      study to determine the actual health risks, is very expensive and requires
      medical and financial justification. The aim of this study was to develop a
      theoretical health risk model, which could be used as a predictive tool to
      determine as accurately as possible from the data available if a complete
      scientific health risk assessment study is justified. The actual amounts of
      pesticides sold in the Vaalharts area by two major pesticide manufacturers were
      used to perform a theoretical health risk assessment. The risks were assessed by
      making use of RISK*ASSISTANT, a computer modeling system and chemical database.
      The United States Environmental Protection Agency's (EPA) health risk model was
      applied to the data to identify the hazards, assess the exposures and dose
      response, and characterize the risks. Three exposure scenarios, namely, the
      ingestion of food and water and the inhalation of air were evaluated. The method
      used to calculate the risks varied according to the type of health hazard and the
      results were characterized accordingly. The acute health effects due to exposure
      to pesticides are well known and the risks are easy to determine. However, the
      risks associated with chronic health hazards were more difficult to calculate.
      For this reason a ranking model was developed which made use ofa point scoring
      system. This model highlights those pesticides which have the greatest
      possibility of causing chronic health effects. From the results it can be
      concluded that very large amounts of pesticides are used in the Vaalharts area
      and that the community might be at risk to chronic health effects. Although the
      theoretical health risk assessment model was successfully used in this study, its
      effectiveness as a predictive tool still has to be proven by a complete
      scientific study.

PMID- 9002434
TI  - Ecotoxicology of organisms adapted to life in temporary freshwater ponds in arid
      and semi-arid regions.
AB  - Hot arid and semi-arid zones are characterized by an abundance of temporary
      ponds. Most of these depend on rain for their existence. These habitats are
      distinguished by fluctuating and unpredictable changes in their hydrological
      regime and of physical and chemical conditions.They contain a uniquely-adapted
      fauna that copes in different ways with changing and often extreme temperatures,
      oxygen levels, pH, salinity and turbidity. A classification is presented of the
      most distinctive adaptations,the various tactics that organisms apply to survive
      dry periods. The main strategies are dormancy (escape in time) and dispersal
      (escape in space). These adaptations may affect the impact of toxicants on
      individuals, populations and communities of temporary ponds. The physiological
      adaptations of species found in temporary ponds are likely to alter the
      sensitivity to pollutants of characteristic species. Results from laboratory
      experiments,for example, suggest that fairy shrimp (Branchiopoda, Anostraca) may
      react differently to heavy metals and pesticides as the standard test species
      Daphnia. Life history strategies influence recovery rates of populations after
      exposure to acutely toxic substances such as pesticides. It is also suggested
      that slow growth and decreased reproductive capacity of organisms caused by
      toxicants may, in ephemeral ponds, result in the failure of annual recruitment.
      Whether assemblages of organisms in temporary ponds are generally more vulnerable
      or more resilient than those in permanent waters or temperate regions could not
      be determined conclusively with the limited data available. Ecological concepts
      for studying the habitat and the development of risk assessment methods for
      temporary ponds are briefly discussed.

PMID- 9002435
TI  - Impacts on nontarget insects of a new insecticide compound used against the
      desert locust [Schistocerca gregaria (Forskal 1775)].
AB  - In 1994, the effects of fipronil, a new insecticide compound of the phenyl
      pyrazol chemical group, was tested against desert locusts during a field
      experiment in Mauritania. The impacts of these spray treatments on nontarget
      Coleoptera and Hymenoptera were also studied. In relation to organophosphorous
      insecticides usually used against grasshoppers and locusts, fipronil appeared
      more effective and persistent. Similar results were obtained for nontarget
      Carabidae and Tenebrionidae which were almost totally eliminated from the treated
      plot. The effects on Hymenoptera varied according the family; Scelionidae and
      Sphecidae seemed to be more affected than Apoidea. Positive and negative aspects
      of fipronil treatments are discussed. Appearing as one of the most convenient
      insecticides to successfully prevent locust outbreaks, at a very early stage of
      invasion under Saharan conditions, fipronil simultaneously induces heavy
      mortality in some nontarget insect groups.

PMID- 9002436
TI  - The impact of insecticides on beneficial arthropods in cotton agro-ecosystems in
      South Africa.
AB  - The unique diversity of beneficial arthropods in South Africa can be regarded as
      an important natural resource in agro-ecosystems as it plays an important role in
      the natural control of insect pests. Insecticide applications reduce the ability
      of these beneficials to regulate cotton pests. In the absence of insecticides,
      average daily predation rates of 37% and 30% of bollworm eggs and larvae
      respectively were found in exclusion experiments. By minimizing the number of
      pesticide applications the combination of the direct negative effect of pesticide
      application on predator populations and secondary pesticide effects such as the
      stimulation of red spider mite populations as a result of predator suppression,
      can be avoided. This would open the option to fully utilize the full pest control
      potential of the natural enemy complex.

PMID- 9002437
TI  - Virulence of the entomopathogenic fungus Metarhizium flavoviride Gams and
      Rozsypal and toxicity of diflubenzuron, fenitrothion-esfenvalerate and profenofos
      cypermethrin to nontarget arthropods in Mauritania.
AB  - Within the framework of the GTZ project, Biological and Integrated Control of
      Locusts and Grasshoppers, a laboratory screening fo rMetarhizium flavoviride
      (strain Mfl 5) blastospore pathogenicity to the nontarget arthropods Pharoscymnus
      anchorago F. (Coleoptera:Coccinellidae), Trachyderma hispida (Forskal)
      (Coleoptera:Tenebrionidae), Palpares cf. tesselatus Rambur
      (Neuroptera:Myrmeleontidae) and Thanatus sp. (Araneae: Philodromidae) was
      conducted in Akjoujt research station, Mauritania. Various larval stages of
      desert locust, Schistocerca gregaria Forskal (Orthoptera:Acrididae), were tested
      as positive controls. The insect growth regulator diflubenzuron was used as a
      reference in the bioassay with P.anchorago. In addition, two organophosphate
      pyrethroid insecticide swidely used in locust control, fenitrothion-esfenvalerate
      (P.anchorago, T. hispida) and profenofos-cypermethrin (Thanatussp.) were tested
      as toxic standards. M. flavoviride was not pathogenic to nontargets, but very
      virulent to S. gregaria. The results provided further evidence that the host
      range of M.flavoviride (Mfl5), a strain isolated from migratory locust in
      Madagascar, is very narrow. Diflubenzuron was toxic to P. anchorago and to S.
      gregaria. The LD50s of both chemical insecticides tested were considerably lower
      than the expected initial environmental concentration. The beneficial P.
      anchorago, a natural enemy of scale insects in date palms, was considered most at
      risk in the course of chemical locust control. The use of mycopesticides to
      control desert locust in date palm plantations offers an environmentally safe and
      economically viable alternative to chemical control.

PMID- 9002438
TI  - Environmental effects of heavy spillage from a destroyed pesticide store near
      Hargeisa (Somaliland) assessed during the dry season, using reptiles and
      amphibians as bioindicators.
AB  - A pesticide store near Hargeisa (Somaliland) was damaged by bombing in May 1988,
      and subsequently looted by local people, who removed and drained drums of
      chemicals. Assessment of the effects of resultant spillage during the dry season,
      March/April 1993, established that pesticides, mainly organochlorines (dieldrin
      and products and BHC isomers)and organophosphates (fenitrothion and malathion)
      had contaminated 3700 sq mof soil at up to 3728.0 (geometric mean 149.0) ppm
      (5180.0 g/m3)total insecticides. Reptiles avoided contamination above 1 ppm, and
      were absent above 10 ppm. Experimental contact with highly contaminated soil
      caused death in lizards-Hemidactylus parkeri and Mabuyas. striata-after 26.5 and
      33. 5 h, respectively (residue levels elevated over 2000-and 149-fold), and 100%
      mortality within 65 min in frogs Tomopterna cryptotis (geometric mean residue
      level elevated 168-fold). Sediment 350 m downstream of the spill contained
      dieldrin at 0.50 ppm (0.03-0.05 ppm after 1.6, to 9.0, km). Whole body residues
      of spillage vicinity lizards were up to 1.52 ppm wet weight (193.6 ppm lipid)
      total insecticides. Geometric mean of 0.36 ppm was elevated fivefold above mean
      background level of Hargeisa lizards in the valley below. Dieldrin and products
      was highest; the level of BHC isomers was also significantly higher than DDT.
      Geometric mean total insecticide level in Chalcides ragazzii and H. parkeri was
      four times higher than in surface-dwelling Pseuderemias smithi. Reptile species
      richness was habitat-influenced. Frogs without abnormalities present in mud of
      river-bed wells indicated uncontaminated ground water (organochlorine residues
      undetected). Low levels in frogs, and of M. s. striata in thevicinity of wells
      [geometric means 0.09 and 0.07 (ranges 0-0.48 and 0.01-0.31) ppm, respectively],
      implied that by 2.7 km downstream of the spill few residues were entering food
      chains.

PMID- 9002439
TI  - Optimization of environmental factors for the biological treatment of
      trinitrotoluene-contaminated soil.
AB  - In earlier studies (Boopathy et al. 1994a, 1994b), soil bacteria present in a TNT
      contaminated site removed 2,4,6-trinitrotoluene (TNT). In this study the optimum
      conditions for the most efficient removal of TNT is discussed. The results
      suggest that the soil bacterial consortium has an optimal pH range of 6-7.
      Maximum growth was observed at pH 7. However, the TNT removal rate was higher at
      pH 6. Studies of the effects of temperature showed that the bacterial consortium
      had maximum metabolic activity at 20 to 22 degrees C (ambient temperature). At a
      higher temperature (37 degrees C) the TNT removal rate dropped significantly. The
      consortium could not use TNT as a nitrogen source but required the addition of
      ammonium. Optimal growth occurred with 0.25 g/L of ammonium chloride. Growing
      cells removed TNT significantly faster rates than resting cells or cell-free
      extract. The operation of soil slurry reactors with the optimal conditions
      suggested that TNT can be removed effectively from the contaminated sites. These
      environmental conditions established as optimal can be used to improve the
      efficiency of large-scale soil slurry reactors for the treatment of soil
      contaminated with TNT.

PMID- 9002440
TI  - Persistence of polycyclic aromatic hydrocarbon components of creosote under
      anaerobic enrichment conditions.
AB  - Anaerobic biodegradation of an artificial mixture of polycyclic aromatic
      hydrocarbons (PAHs), which simulates the PAH component of creosote, was examined
      under methanogenic, sulfidogenic, and nitrate-reducing conditions using creosote
      contaminated sediment as the source of inoculum. PAH degradation, CH4 formation
      and ion reduction were monitored for up to one year. Despite demonstrating active
      methanogenic and nitrate-reducing anaerobic bacterial communities, only limited
      degradation of a few PAHs was observed. Under methanogenic conditions limited
      degradation of all bicyclic (naphthalene, 1-and 2-methylnaphthalene, biphenyl,
      and 2,6-dimethylnaphthalene) and one tricyclic PAH, anthraquinone, was detected.
      2-Methylanthracene was apparently degraded under nitrate-reducing conditions.
      Anthraquinone declined in sulfate enrichments, but this decline was not dependent
      upon sulfate reduction. None of the 4- or 5-ring PAHs were degraded under any of
      the enrichment conditions. These data indicate that under the anaerobic
      conditions tested there is only a limited potential to degrade PAHs which must be
      considered when proposing bioremediation technologies for PAH-contaminated sites,
      especially if high-molecular-weight PAHs are present.

PMID- 9002442
TI  - Tolerance of the nematode Caenorhabditis elegans to pH, salinity, and hardness in
      aquatic media.
AB  - The toxicity of many chemicals depends on the physical conditions of the test
      environment, and any change or adjustment made to the tests can alter the
      results. Therefore it is important to establish the sensitivity of the test
      organism over a range of test conditions to determine when it is necessary to
      make adjustment and to what extent. In this study, we established the tolerance
      range of the nematode Caenorhabditis elegans for pH, salinity and hardness using
      24- (without food source) and 96-h (with food source) aquatic toxicity tests. The
      tests were performed in two media: K-medium and moderately hard reconstituted
      water (MHRW). C.elegans has high tolerance under these test conditions. In K
      medium worms survived a pH range of 3.1 to 11.9 for 24 h and 3.2 to 11.8 for 96 h
      without significant (p > 0.05) lethality. In MHRW the pH range was 3. 4 to 11.9
      for 24 h and 3.4 to 11.7 for 96 h. Salinity tolerance tests were approximated
      with NaCl and KCl individually. Up to 15.46 g/L NaCl and 11.51 g/L KCl were
      tolerated by C. elegans in K-medium without significant lethality (p> 0.05). In
      MHRW higher salt concentrations were tolerated; about 20.5 g/L NaCl and 18.85 g/L
      KCl did not show any adverse effect compared to control. Hardness tolerance was
      tested by adding NaHCO3. The nematode could tolerate 0. 236 to 0.246 g/L of
      NaHCO3. The high tolerance of C. elegans to these test conditions (pH, salinity,
      and hardness) allows more versatility than other organisms commonly used in
      aquatic toxicity tests. It also allows the monitoring of effluents and receiving
      waters from freshwater or estuarine sources without dilution or adjustment.

PMID- 9002441
TI  - Effect of subsurface drains on runoff losses of metolachlor and trifluralin from
      Mississippi River alluvial soil.
AB  - Subsurface drains reduced runoff losses of metolachlor and trifluralin from plots
      on Mississippi River alluvial soil planted with soybean. The drains reduced
      metolachlor runoff losses by 90% and trifluralin losses by 57%. Concomitantly,
      runoff volume was reduced 24% and soil erosional losses by 75%. The large
      reduction of metolachlor losses in runoff was due to a first event from the
      nondrained plot that was characterized by high chemical concentration, a
      characteristic that was not duplicated in the corresponding events from the
      drained plots. Due to low sediment concentrations in runoff and to low water
      solubility,trifluralin loss in runoff, even from the nondrained treatment, was
      less than 0.2% of the application.

PMID- 9002444
TI  - Functional characterization of a chicken major histocompatibility complex class
      II B gene promoter.
AB  - A 0.7 kilobase (kb) DNA fragment from the 5' flanking region of a chicken major
      histocompatibility complex (MHC) class II B gene was cloned into chloramphenicol
      acetyltransferase (CAT) reporter vectors and was transfected into a chicken
      macrophage cell line that expresses a low level of MHC class II antigens.
      Positive orientation-dependent promoter activity of the chicken DNA was evident
      in a reporter construct containing an SV40 enhancer. Deletion analysis of this
      0.7 kb DNA fragment revealed a short fragment in the 3' end that was crucial for
      the promoter function and negative regulatory elements (NRE) located further
      upstream. The conserved MHC class II X and Y boxes did not have a significant
      effect on promoter activity. Sequence analysis of the 0.7 kb class II B gene
      upstream region suggests possible involvement of interferon (IFN), E twenty-six
      specific (ETS)-related proteins, and other factors in regulating this promoter. A
      chicken T-cell line culture supernatant increased surface expression of MHC class
      II antigens, as well as class II promoter activity, in this macrophage cell line.
      This first functional characterization of a chicken MHC class II B gene promoter
      will aid in understanding the regulatory mechanisms that control the expression
      of these genes.

PMID- 9002445
TI  - Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding
      modes.
AB  - Previous studies have defined two different peptide binding motifs specific for
      HLA-A*0101. These motifs are characterized by the presence of tyrosine (Y) at the
      C-termini of 9-mer and 10-mer peptides, and either a small polar or hydrophobic
      (S, T, M) residue in position 2, or a negatively charged (D or E) residue in
      position 3. In this study, the structural requirements for peptide binding to
      A*0101 have been further analyzed by examining the binding capacity of large sets
      of peptides corresponding to naturally occurring sequences which bore one or the
      other of these two A*0101-specific motifs. By correlating the presence of
      specific residue types at each position along the peptide sequence with increased
      (or decreased) binding affinity, the prominent influence of secondary anchor
      residues was revealed. In most cases, the two anchors in positions 2 and 3 appear
      to act synergistically. With the exception of the DE3 submotif in 9-mer peptides,
      a positive role for aromatic residues in position 1 and the center of the peptide
      (positions 4 or 5 of 9- or 10-mer peptides, respectively), and proline at C-3,
      were also consistently detected. However, secondary anchor residues also appear
      to differ significantly between the two different submotifs, demonstrating that
      A*0101 can utilize alternative modes in binding its peptide ligands. According to
      these analyses, specific refined submotifs were also established, and their merit
      verified by independent sets of potential A*0101 binding peptides. Besides
      providing useful insight into the nature of the interaction of the A*0101 allele
      with its peptide ligands, such refined motifs should also facilitate accurate
      prediction of potential A*0101-restricted peptide epitopes.

PMID- 9002443
TI  - Structure and diversity of the T-cell receptor alpha chain in the Mexican
      axolotl.
AB  - Polymerase chain reaction was used to isolate cDNA clones encoding putative T
      cell receptor (TCR) alpha chains in an amphibian, the Mexican axolotl (Ambystoma
      mexicanum). Five TCRalpha-V chain-encoding segments were identified, each
      belonging to a separate family. The best identity scores for these axolotl
      TCRalpha-V segments were all provided by sequences belonging to the human
      TCRalpha-V1 family and the mouse TCRalpha-V3 and TCRalpha-V8 families. A total of
      14 different TCRA-J segments were identified from 44 TCRA-V/TCRA-J regions
      sequenced, suggesting that a large repertoire of TCRA-J segments is a
      characteristic of most vertebrates. The structure of the axolotl CDR3 alpha chain
      loop is in good agreement with that of mammals, including a majority of small
      hydrophobic residues at position 92 and of charged, hydrophilic, or polar
      residues at positions 93 and 94, which are highly variable and correspond to the
      TCRA-V/J junction. This suggests that some positions of the axolotl CDR3 alpha
      chain loop are positively selected during T-cell differentiation, particularly
      around residue 93 that could be selected for its ability to makes contacts with
      major histocompatibility complex-associated antigenic peptides, as in mammals.
      The axolotl Calpha domain had the typical structure of mammalian and avian Calpha
      domains, including the charged residues in the TM segment that are thought to
      interact with other proteins in the membrane, as well as most of the residues
      forming the conserved antigen receptor transmembrane motif.

PMID- 9002446
TI  - Binding of 8-mer to 11-mer peptides carrying the anchor residues to slow
      assembling HLA class I molecules (HLA-B*5101).
AB  - The binding of 303 8-mer to 11-mer peptides carrying the anchor residues at P2
      and the C-terminus to HLA-B*5101 molecules was examined by a stabilization assay
      in which peptides were incubated with RMA-S-B*5101 cells at 26 degrees C for 3 h.
      Analysis of the binding of these peptides to HLA-B*5101 molecules showed that Pro
      and Ala at P2, and Ile, Val, and Leu at the C-terminus functioned as anchor
      residues, while Gly at P2 and Met at the C-terminus were weak anchors. Pro was a
      stronger anchor residue than Ala at P2, while Ile was the strongest anchor at the
      C-terminus. Among 8-mer to 11-mer peptides, the 9-mer peptides showed the
      strongest binding to HLA-B*5101 molecules. This is in contrast to our recent
      findings that 10-mer and 11-mer peptides bind to HLA-B*3501 molecules as
      effectively as 9-mer peptides. Since both HLA class I molecules have the same B
      pocket and the binding peptides carry the same anchor residues, it is assumed
      that the structure of the F-pocket may restrict the length of binding peptides.
      The ability of HLA-B*5101 binding peptides to stabilize the HLA-B*5101 molecules
      was markedly lower than that of HLA-B*3501 binding peptides to stabilize the HLA
      B*3501 molecules. It is known that HLA-B*5101 is a slow assembling molecule,
      while HLA-B*3501 assembles rapidly. The results imply that the slow assembling of
      HLA-B*5101 molecules results from the low affinity of peptides to HLA-B*5101
      molecules.

PMID- 9002447
TI  - Isolation of a B-cell-specific promoter for the human class II transactivator.
AB  - The class II transactivator (CIITA) is essential for the expression of major
      histocompatibility complex (MHC) class II antigens. The tissular patterns of
      CIITA and MHC class II gene expression are tightly correlated: CIITA mRNA is
      highly expressed in B cells, and is induced by interferon gamma (IFN-gamma) in
      macrophage and epithelial cell lines. We first isolated two overlapping cosmids
      encoding human CIITA which, when co-transfected, are able to restore MHC class II
      expression in a B-lymphoblastoid cell line (B-LCL) defective for CIITA.
      Subsequently, a 1.8 kilobase (kb) fragment of the CIITA promoter was isolated and
      sequenced. A motif presenting a strong similarity to an initiator was detected,
      as well as putative binding sites for Sp1, GATA-2, LyF-1, ets-1, AP1, and MZF1
      transcription factors, and two GAS motifs. When introduced in front of a
      luciferase reporter gene, this promoter is able to direct a high luciferase
      activity in a human B-LCL. In contrast, luciferase expression was not stimulated
      after IFN-gamma treatment when the construct was transfected in macrophage or in
      epithelial cell lines. However, an induction of the human CIITA gene was observed
      in mouse macrophage and fibrosarcoma cell lines, when the cells were transfected
      with a cosmid containing the human CIITA gene, but lacking the 1.8 kb promoter
      described above. Taken together, these data suggest the existence of an
      intragenic promoter driving an IFN-gamma-inducible expression of CIITA.

PMID- 9002448
TI  - Fine mapping of 12 microsatellites and two new recombinants in the distal H2
      complex on mouse chromosome 17.

PMID- 9002449
TI  - Peptide binding motifs of the MHC class I molecules (RT1.Al) of the Lewis rat.

PMID- 9002450
TI  - A new human transporter associated with antigen processing alleles encodes a
      large C-terminal protein domain.

PMID- 9002451
TI  - Transposon-induced splicing defect in the rat nude gene.

PMID- 9002452
TI  - Characteristics and significance of the amorphous state in pharmaceutical
      systems.
AB  - The amorphous state is critical in determining the solid-state physical and
      chemical properties of many pharmaceutical dosage forms. This review describes
      the characteristics of the amorphous state and some of the most common methods
      that can be used to measure them. Examples of pharmaceutical situations where the
      presence of the amorphous state plays an important role are presented. The
      application of our current knowledge to pharmaceutical formulation problems is
      illustrated, and some strategies for working with amorphous character in
      pharmaceutical systems are provided.

PMID- 9002453
TI  - Evaluation of the hairless rat as a model for in vivo percutaneous absorption.
AB  - Percutaneous absorption of topically applied mannitol and progesterone was
      compared in vivo with the hairless and hairy rat. Urinary excretion and skin
      concentration profiles after topical application of mannitol demonstrated that
      hairless rat skin was a "leakier" barrier to percutaneous absorption of polar
      compounds than was hairy rat skin, independent of formulation. Liposomal, but not
      aqueous mannitol was retained in hairy rat skin (> 0.5% after 12 h), whereas only
      negligible amounts were retained in hairless rat skin, regardless of formulation.
      Progesterone absorption from hydroalcohol and liposomal formulations into
      hairless rat skin was about five times greater than that in hairy rat skin. Skin
      delipidization by acetone resulted in a dramatic reduction in the cutaneous
      barrier to systemic mannitol absorption, which was much more pronounced in hairy
      than in hairless rat skin. Histological findings of patulous cysts and enlarged,
      highly vascularized sebaceous glands in the hairless rat suggested that these
      structures may enhance polar pathways and provide a lipophilic reservoir relative
      to the fully developed hair follicles of the hairy rat. Collectively, the results
      document percutaneous absorption differences as a function of animal model, and
      also suggest that follicular structures make a major contribution to passive
      percutaneous absorption.

PMID- 9002454
TI  - Determination of diffusion coefficients of sodium p-aminosalicylate in sheep
      nasal mucosae and dialysis membranes by Fourier transform infrared horizontal
      attenuated total reflectance spectroscopy.
AB  - Fourier transform infrared horizontal attentuated total reflectance (FT-IR-H-ATR)
      spectroscopy was employed to determine the diffusion coefficients of sodium p
      aminosalicylate (PAS) in sheep nasal mucosae and dialysis membranes. The system
      configuration, which comprises a closed system with an aqueous layer and a
      membrane layer, represents diffusion from a solution of limited volume. Data
      analysis involved fitting a truncated (seven term) Fourier series to the total
      mass transport into the membrane as a function of time. Comparison of diffusion
      coefficients of PAS in dialysis membranes obtained by this technique to those
      obtained by a standard steady-state permeation method showed excellent agreement.
      Apparent diffusion coefficients were approximately 4.33 (+/- 0.38) x 10(-7) and
      approximately 9.62 (+/- 5.30) x 10(-7) cm2/s for dialysis membranes and sheep
      nasal mucosae, respectively. These values are substantially smaller than the
      diffusion coefficient of PAS in aqueous solution, indicating that the rate
      limiting step was diffusion in the membrane. The effect of purified gastric mucin
      solution (concentration up to approximately 6% w/v) on the apparent diffusion
      coefficient of PAS in the membranes was also investigated. The results showed no
      statistically significant change in the apparent diffusion coefficient in the
      presence of mucin for either sheep nasal mucosae or dialysis membranes. Although
      it was reported that mucin in solution retards the diffusion of PAS as compared
      to buffer alone, the mass transport within the membrane was the rate-limiting
      step for this hydrophilic compound.

PMID- 9002455
TI  - Nondestructive viscoelastic analysis of anisotropy in compressed tablets.
AB  - A nondestructive procedure for determining anisotropy levels in compressed
      tablets was developed based on dynamic stress/strain measurements of
      viscoelasticity in the axial and radial directions. An instrument was designed
      and built capable of 10 nm resolution of strain and operating over the frequency
      range 1-64 Hz. Tablets of 11 pharmaceutical excipients and drugs, representing
      both plastic and brittle materials, were found to behave as three-parameter
      viscoelastic solids in both the axial and radial directions. Elastic and viscous
      parameters were computed, based on frequency dependence over the range studied,
      and were found to differ greatly in the axial and radial directions. Degrees of
      anisotropy, defined as the ratio of the uncoupled spring parameters in the radial
      vs the axial direction, were found to range from 2- to 12-fold over the materials
      studied. These levels of anisotropy are thought to be typical of tablets
      manufactured in a rotary press under normal conditions. Measurements of this type
      can be easily made routinely as a further means of quality control and reflect an
      important feature of the internal structure of compressed tablets.

PMID- 9002456
TI  - Evidence for a passive diffusion mechanism for sparfloxacin uptake at the brush
      border membrane of the human intestinal cell-line Caco-2.
AB  - The oral uptake of the new fluoroquinolone sparfloxacin was evaluated in the
      human epithelial cell line Caco-2 that possesses intestinal enterocyte-like
      properties when cultured in vitro. The uptake of [14C]-sparfloxacin across the
      apical membrane of Caco-2 cell monolayers was rapid and similar at 25 and 37
      degrees C. The initial rate of sparfloxacin uptake was not saturable in the 1-200
      microM range and was unaffected by metabolic inhibitors (depletion of ATP store
      or ouabain), indicating that uptake was energy-independent. The absence of
      competition with other fluoroquinolones or aminocephalosporins showed that the
      absorption of sparfloxacin did not involved the H+-coupled dipeptide transport
      system. Our findings suggest that the apical uptake of sparfloxacin by Caco-2
      cells mainly involves diffusion, a finding that is in agreement with the high
      lipophilicity of sparfloxacin. The intracellular-to-extracellular concentration
      ratio of approximately 14 after 60 min of incubation suggests the existence of
      important binding of sparfloxacin to cell components.

PMID- 9002457
TI  - Concentration-EEG effect relationship of propofol in rats.
AB  - Propofol is a unique highly lipid-soluble anesthetic that is formulated in a fat
      emulsion (Diprivan) for intravenous (i.v.) use. It has the desirable properties
      of rapid onset and offset of effect following rapid i.v. administration and
      minimal accumulation on long-term administration. Based on physicochemical
      properties and preliminary brain solubility data, propofol should have an
      extended effect-site turnover and a resulting prolonged effect. However, a
      preliminary study in humans has reported a rapid blood-brain equilibration half
      time (T1/2 kE0) of only 2.9 min. We used a chronically instrumented rat model to
      examine the unique disposition and electroencephalographic (EEG) pharmacodynamics
      of propofol. Although the pharmacokinetics were variable, there was low
      interindividual variability in the concentration-EEG effect relationship. The
      duration of EEG sleep was 26 (+/- 44% CV) min following 11-15 mg/kg doses of
      propofol. The T1/2 kE0 was 1.7 (+/- 32%) min. Apparent effect-site concentrations
      of 0.5-1 microg/mL were required to maintain sleep in rats. Like other general
      anesthetics, the concentration-EEG effect relationship of propofol is biphasic.
      At a propofol concentration of 0.6 (+/- 35%) microg/mL, the number of EEG waves/s
      was maximal at 175% of baseline awake state. Further increases in the
      concentration of propofol depressed EEG activity until complete suppression
      occurred at 7 (+/- 22%) microg/mL.

PMID- 9002458
TI  - Parameter estimability of biphasic response models.
AB  - Pharmacodynamics of general anesthetic agents generally exhibit biphasic
      concentration-effect relationships (i.e., an activation phase at low
      concentrations and inhibition at higher concentrations). These relationships are
      usually characterized with biphasic models constructed from various combinations
      and modifications of the nonlinear sigmoid E(MAX) model. We tested and quantified
      the parameter estimability of the simplest additive biphasic pharmacodynamic
      models by a Monte Carlo method. The estimated model parameters were used to
      calculate descriptors of the concentration-effect data. Parameters and
      descriptors were compared with their true values. When the IC50/EC50 ratio was
      low (<10), E(MAX), EC50, and IC50 were poorly estimated (high coefficient of
      variation and pronounced bias). However, the fit to the data was excellent, and
      the data descriptors calculated from the estimated model parameters demonstrated
      high precision and accuracy. Baseline effect (E0) was estimated with good
      precision and accuracy. As the IC50/EC50 ratio was increased, the estimability of
      model parameters and data descriptors improved, with the data descriptors
      continuing to be more estimable than model parameters. Thus, model parameters
      become estimable when there is sufficient separation between EC50 and IC50 to
      produce a plateauing of peak effect (activation), which can be observed directly
      from the data signature. Data descriptors are not subject to this limitation and
      thus may serve as better metrics for summarizing concentration-effect
      relationships.

PMID- 9002459
TI  - Comparison of plasma and free tissue levels of ceftriaxone in rats by
      microdialysis.
AB  - Ceftriaxone has a very high plasma protein binding (up to 98%) that is saturable
      and decreases with higher concentrations. This high protein binding results in
      high concentrations in plasma that are frequently related to the anti-infective
      activity. However, because only the free fraction of the drug is
      pharmacologically active and most of the infections are located in the tissues,
      it is more relevant to evaluate unbound concentrations in the interstitial space.
      Plasma and tissue pharmacokinetics of ceftriaxone in rats after single
      intravenous administration were investigated at two different concentrations (50
      and 100 mg/kg). Both plasma and tissue samples were taken simultaneously from the
      same animal and analyzed by reversed-phase high-performance liquid
      chromatography. Free tissue levels in the thigh muscle were measured by
      microdialysis. The concentration in plasma is much higher than the free
      concentration in tissue. After determination of nonlinear protein binding by
      microdialysis and including these parameters in the pharmacokinetic model, it is
      possible to predict free concentrations in the interstitial space from plasma
      levels for any given dose.

PMID- 9002460
TI  - Introduction of solvent-accessible surface area in the calculation of the
      hydrophobicity parameter log P from an atomistic approach.
AB  - A conventional atomistic approach of estimating molecular hydrophobicity (log P)
      was improved by taking into account the proximity effect of substituent groups as
      well as the importance of solute-solvent interaction in the partition phenomena.
      The new method reassigns atomic parameters when the molecule is fully exposed to
      surrounding solvent. Each atom in a molecule contributes to the log P by an
      amount of its atomic parameter multiplied by the degree of exposure to the
      surrounding solvent. This degree of exposure is calculated from the solvent
      accessible surface area (SASA). In carrying out actual calculations, the
      necessary parameters were determined with the log P values of 500 compounds that
      were used as training data. This method, which may be called SASA-scaled
      atomistic method, gave satisfactory results when compared with the original
      method of estimating log P from atomic parameters. The ability of the new method
      to predict log P for compounds other than those used as the training data was
      also tested. The newly proposed SASA-scaled atomistic method was also compared
      with other methods available for the calculation of log P. The SASA-scaled
      atomistic method gave better estimations from fewer training data. Finally, the
      ability of the proposed method to predict differences in log P for steric isomers
      was tested. The new method was superior to other methods, including CLOGP, a
      widely accepted method of estimating log P for a variety of compounds.

PMID- 9002461
TI  - Solid state stability studies of model dipeptides: aspartame and
      aspartylphenylalanine.
AB  - Some solid-state pharmaceutical properties and the solid-state thermal stability
      of the model dipeptides aspartame (APM) and aspartylphenylalanine (AP), have been
      investigated. Studies by differential scanning calorimetry (DSC), thermal
      gravimetric analysis (TGA), high-performance liquid chromatography, powder X-ray
      diffraction, and optical microscopy have shown that the dipeptides undergo solid
      state intramolecular aminolysis of the type, solid --> solid + gas. This reaction
      was observed for APM at 167-180 degrees C with the liberation of methanol and for
      AP at 186-202 degrees C with the liberation of water. The exclusive solid product
      of the degradation reaction of both dipeptides is the cyclic compound 3
      (carboxymethyl)-6-benzyl-2,5-dioxopiperazine. The rates of the degradation
      reactions were monitored by isothermal TGA and by temperature-ramp DSC and were
      found to follow kinetics based on nucleation control with activation energies of
      about 266 kJ mol(-1) for APM and 234 kJ mol(-1) for AP.

PMID- 9002462
TI  - Nuclear magnetic resonance investigations of the inclusion complexation of
      gliclazide with beta-cyclodextrin.
AB  - The formation of the gliclazide-beta-cyclodextrin (GL-beta-CD) inclusion compound
      has been studied in the liquid state by phase solubility techniques and by 1H and
      13C NMR spectroscopy. From the initial straight portion of the solubility curve
      (Bs type), the value of the apparent stability constant (Kc) was calculated as
      1094 M(-1). The nuclear magnetic resonance studies confirm that GL yields a
      complex with beta-CD in aqueous medium, which is mainly due to the penetration of
      the azabicyclooctyl group of GL into the cavity of beta-CD. The study of the
      monodimensional nuclear Overhauser effect (NOE) of the H3 proton of CD has shown
      that the tolyl group also interacts with CD, but to a lesser extent than the
      azabicyclooctyl moiety. Finally, the application of the continous variation
      technique confirmed the 1:2 drug:CD stoichiometry of the complex.

PMID- 9002463
TI  - SK&F 97426-A: a novel bile acid sequestrant with higher affinities and slower
      dissociation rates for bile acids in vitro than cholestyramine.
AB  - SK&F 97426-A is a novel bile acid sequestrant that is threefold more potent than
      cholestyramine at increasing bile acid excretion in the hamster. SK&F 97426-A is
      a quaternary alkylammonium polymethacrylate that was selected for comparison with
      cholestyramine in vivo because of its superior in vitro bile acid binding
      properties. Association, dissociation, affinity, and capacity experiments were
      performed under physiologically relevant conditions with the most abundant bile
      acids found in human bile. The bile acids came to equilibrium with SK&F 97426-A
      and cholestyramine within approximately 30 min and 6 min, respectively. SK&F
      97426-A and cholestyramine had similar capacities for all the bile acids (between
      2.5 and 4 mmol/g) and both had similar, very high affinities and slow
      dissociation rates for the dihydroxy bile acids. However, SK&F 97426-A had much
      higher affinities for the trihydroxy bile acids glycocholic acid and taurocholic
      acid than did cholestyramine. Dissociation of glycocholic acid and taurocholic
      acid from SK&F 97426-A was also much slower (27 and 25%, respectively,
      dissociated after 60 min) than from cholestyramine (89 and 84%, respectively,
      dissociated after 60 min). The higher affinities and slower dissociation rates of
      the trihydroxy bile acids for and from SK&F 97426-A probably account for the
      increased potency of SK&F 97426-A over cholestyramine in vivo.

PMID- 9002464
TI  - Continuous flow mucosal cells for measuring the in-vitro permeability of small
      tissue samples.
AB  - Continuous-flow chambers are described for the measurement of permeability of
      small tissue samples. The design incorporates a large-capacity donor chamber to
      permit adequate loading of the applied compound and a low-volume (0.3 mL)
      receiving chamber that ensures rapid removal of penetrant at relatively low (1.5
      mL/h or less) pumping rates. Different sized support disks allow tissue biopsies
      as small as 4 mm in diameter to be utilized. Comparisons of flux and permeability
      constants (Kp) for water across oral mucosa indicate that there was no
      significant difference between values obtained for 10- and 4-mm biopsies.
      Comparisons of flux and Kp values for porcine oral mucosa and a synthetic
      membrane between continuous flow and conventional, side-by-side chambers
      indicated that the latter values were significantly lower, suggesting stasis and
      inefficient removal of perfusate in the side-by-side design. The Kp values for
      water obtained in the continuous-flow chambers with pig skin were similar to
      those published elsewhere for human skin.

PMID- 9002465
TI  - Influences of 1-dodecylazacycloheptan-2-one on permeation of membranes by weak
      electrolytes. 1. Theoretical analysis of weak electrolyte diffusion through
      membranes and studies involving silicone rubber membranes.
AB  - The pH dependency of permeation of weak electrolytes allows inferences to be made
      about the barrier characteristics of membranes. The influences of enhancers on pH
      permeation profiles promise further mechanistic enlightenment. To explore issues
      of weak electrolyte mass transfer, a steady-state mathematical model for a
      hydrophobic membrane with aqueous pores existing in series with aqueous phases,
      presently a popular depiction of the skin and other biological barriers, has been
      developed. The case in which there are no pores is then considered theoretically
      and in studies involving the mass transfer of benzoic acid across silicone rubber
      membranes. Specifically, the flux of [14C]benzoic acid across Silastic sheeting
      as a function of pH was investigated. This isotropic membrane's behavior
      conformed to expectations drawn from the model in that the un-ionized species
      penetrated in proportion to benzoic acid's prevailing state of ionization, the
      membrane being all but impenetrable to the benzoate anion. The enhancer, 1
      dodecylazacyclo-heptan-2-one (Azone), was then applied to the membrane in
      emulsions of increasing concentration. There were two important consequences of
      such application. First, the un-ionized species of benzoic acid partitioned into
      the emulsion droplets, lowering the activity of the permeant in the emulsion's
      continuous phase. Second, Azone was imbibed to a degree into the polymeric
      membrane, significantly altering the permeability of the silicone rubber of which
      it is composed. The former influence had to be carefully factored out in order to
      delineate Azone's intrinsic enhancing effects on the membrane. The silicone
      rubber membrane system served well as a model for study of the enhancing effects
      of Azone on a wholly hydrophobic barrier, establishing a basis for the analysis
      of the actions of enhancers such as Azone on more complex, multiphasic biological
      barriers.

PMID- 9002466
TI  - Slow release from a coated sphere with slight deformations of coating film and
      drug matrix.
AB  - This paper, a continuation of our previous work, is a presentation of the effects
      of slight deformations of both the coating film and the drug matrix on the
      concentration distributions and the slow release characteristics of a coated drug
      particle. The coated particle shape, in practice, is not perfectly spherical.
      With restriction of the deformation shape functions considered, it is noted that
      if the deformation is slight or if only the average release rate is of interest,
      the effects of shape deformation are secondary. Otherwise, the shape deformation
      can have a significant effect on the concentration profiles and/or the release
      rate from different parts of the particle surface. The deformations of both
      coating film and the drug matrix could introduce a greater deviation from the
      spherical case than those considering only coating film or drug matrix shape
      deformation.

PMID- 9002467
TI  - Residual solvents in biodegradable microparticles. Influence of process
      parameters on the residual solvent in microparticles produced by the aerosol
      solvent extraction system (ASES) process.
AB  - Different batches of microparticles were produced by the aerosol solvent
      extraction system (ASES) utilizing the extraction properties of supercritical
      carbon dioxide. Using a central composite design, the influence of production
      conditions such as spraying rate of the polymer solution and pump rate of the
      circulating carbon dioxide phase, on the characteristics of microparticles was
      studied. The experiments were carried out with regard to the residual solvent in
      the particles, the residual methylene chloride in the carbon dioxide flow of the
      ASES, the particle size, the morphology, and the yield. The results showed an
      influence of the pump rate of carbon dioxide on the yield, on the residual
      solvent in the microparticles, and on the circulating carbon dioxide. There was
      no major influence of the production conditions on the size and morphology of the
      microparticles, indicating that the ASES process seems to be a precipitation
      process.

PMID- 9002468
TI  - Partition coefficients of indoles and betacarbolines.
AB  - Partition coefficients for substituted indoles and betacarbolines were determined
      in octan-1-ol/water and cyclohexane/water. A comparative study of the results in
      both systems allows us to discuss the effects played by the different molecular
      structures, substituents, and aromaticity on the distribution properties of these
      compounds. In particular, the hydrogen-bond donor (HBD) and hydrogen-bond
      acceptor (HBA) properties of these solutes were characterized and compared with
      those of structurally related compounds. The Abraham solute descriptors were
      estimated and partition coefficients (log P) calculated and compared with the
      experimental values. The results show that the HBD properties are similar for
      indoles and betacarbolines, and the HBA capacity, as expected, is significantly
      enhanced by the contribution of the extra pyridinic or piperidinic ring in
      betacarbolines. The effects of the substituent groups are presented in relation
      to their contribution to the distribution properties of the compounds studied.

PMID- 9002469
TI  - Modeling of drug release from erodible tablets.
AB  - A general mathematical model was developed to describe drug release from erodible
      tablets undergoing surface erosion. The model (which is based on the Hopfenberg
      equation) takes into account the three dimensions of a tablet dosage form. The
      model enables the characterization of the release kinetics by one or two erosion
      rate constants depending on the hydrodynamic conditions of the system. The model
      can be used to compare the release rates of the drug within different batches
      produced under different conditions. The model was utilized to evaluate some
      factors affecting the release rate from erodible tablets consisting of
      hydroxypropyl methylcellulose and amoxicillin. The release data of amoxicillin
      measured from the whole tablet followed the equation developed. Amoxicillin
      release data measured from the planar surface of the tablet appeared to follow
      zero-order kinetics as predicted by theory for drug release from an erodible
      device maintaining constant surface area with time.

PMID- 9002470
TI  - Immunohistochemical localization of insulin-degrading enzyme along the rat
      intestine, in the human colon adenocarcinoma cell line (Caco-2), and in human
      ileum.
AB  - Insulin-degrading enzyme (IDE) has been implicated in the intracellular
      degradation of insulin in insulin target cells. Knowledge of the existence of
      this enzyme in the intestine will be beneficial to the achievement of clinical
      oral efficacy of insulin. A comparative study was conducted with rat intestine,
      human colon adenocarcinoma (Caco-2) cells, and human ileum. Confocal microscopy
      analysis using the anti-IDE antibody showed that IDE was localized in the mucosal
      cells of rat and human intestines, as well as in Caco-2 cells. Immunostaining of
      this enzyme was homogeneous throughout the cell excluding nucleus, indicating a
      typical cytosolic distribution in rat and human enterocytes and in Caco-2 cells.

PMID- 9002471
TI  - Protein-binding high-performance frontal analysis of (R)- and (S)-warfarin on HSA
      with and without phenylbutazone.
AB  - Applicability of high-performance frontal analysis (HPFA) to the stereoselective
      study of drug-drug interaction upon plasma protein binding has been investigated.
      Racemic warfarin and phenylbutazone were used as model drugs. An on-line
      HPFA/HPLC system consisting of a HPFA column (diol-silica column), an extraction
      column, and a chiral separation column was developed, and human serum albumin
      solution containing racemic warfarin and/or phenylbutazone was injected directly
      to the HPFA column. When the injection volume was large enough, the binding
      equilibrium in the sample solution was reproduced in the column, and consequently
      a plateau region appeared on the chromatogram. This plateau region contains
      unbound drug(s). A given volume of eluent in the plateau part was transferred
      into the extraction column by column-switching. The concentrated drug(s) was then
      transferred to the chiral separation column to determine the unbound
      concentrations of the enantiomers and/or the competitor. The results agreed with
      those obtained by a conventional ultrafiltration-HPLC method. The influence of
      phenylbutazone upon the protein binding of warfarin is enantioselective. In
      warfarin and human serum albumin mixed solution, the unbound concentration of (R)
      warfarin was 1.22 times higher than that of the S-isomer. By addition of
      phenylbutazone, the unbound concentration of (S)-warfarin increased more than
      that of (R)-warfarin, resulting in the reversed enantioselectivity, i.e., the
      unbound concentration of (S)-warfarin became 1.19 times larger than that of (R)
      warfarin. The present method was also applicable to human plasma samples.

PMID- 9002474
TI  - Percutaneous absorption of vanilloids: in vivo and in vitro studies.
AB  - The percutaneous absorption of three highly lipophilic analogs of capsaicin-
      vanillylnonanamide (VN), olvanil, and NE-21610--was measured in vivo in the
      CD:VAF rat, and in vitro through excised CD: VAF and SkH:Fz rat skin and human
      cadaver skin. Absorption and skin metabolism were monitored by radiolabel
      techniques. The rank order of penetration in all species was VN > olvanil > NE
      21610, in accordance with that expected from their physical properties. Rat skin
      was more permeable than human skin by factors ranging from 4 to 8 for VN, 10 to
      20 for olvanil, and approximately 10 to 100 for NE-21610. All three compounds
      were extensively metabolized during passage through fresh SkH:Fz rat skin, with
      the primary route of degradation for at least two of the compounds involving
      hydrolysis of the amide bond (the metabolites of NE-21610 were not identified).
      For the in vitro studies a range of receptor solutions was employed to determine
      a set of conditions that best mimicked in vivo absorption. The results with
      phosphate-buffered saline containing a preservative and 1-6% polyoxyethylene-20
      oleyl ether (Oleth-20) were in good agreement with in vivo results for all three
      compounds for periods up to 24 h post-dose; after this time, in vivo absorption
      rates declined but in vitro rates remained relatively constant. Buffered saline
      or saline containing 0.5% bovine serum albumin led to marked underestimates of in
      vivo penetration for olvanil and NE-21610, whereas a 1:1 ethanol: water solution
      led to gross overestimates of the in vivo absorption rates for all three
      compounds.

PMID- 9002472
TI  - Noninvasive in vivo monitoring of drug release and polymer erosion from
      biodegradable polymers by EPR spectroscopy and NMR imaging.
AB  - Biodegradable polymers have attracted much attention as implantable drug delivery
      systems. Uncertainty in extrapolating in vitro results to in vivo systems due to
      the difficulties of appropriate characterization in vivo, however, is a
      significant issue in the development of these systems. To circumvent this
      limitation, noninvasive magnetic resonance techniques, electron paramagnetic
      resonance (EPR) and magnetic resonance imaging (MRI), were applied to
      characterize drug release and polymer degradation in vitro and in vivo. MRI makes
      it possible to monitor water content, tablet shape, and response of the
      biological system such as edema and encapsulation. The results of the MRI
      experiments give the first direct proof in vivo of postulated mechanisms of
      polymer erosion. Using nitroxide radicals as model drug releasing compounds,
      information on the mechanism of drug release and microviscosity inside the
      implant can be obtained by means of 1.2 GHz EPR spectroscopy. To be able to
      attribute nitroxide mobility to a particular layer of the implant, sandwich-like
      tablets were manufactured, taking advantage of the distinct spectral features of
      nitroxides containing different isotopes of nitrogen (15N vs 14N). The use of
      both noninvasive methods to monitor processes in vivo leads to new insights in
      understanding the mechanisms of drug release and polymer degradation.

PMID- 9002473
TI  - Modeling the crystal morphology of alpha-lactose monohydrate.
AB  - Molecular modeling techniques using attachment energy calculations have been
      applied, for the first time to our knowledge, to simulate the morphology of an
      organic hydrate: alpha-lactose monohydrate. Calculation of the strong
      intermolecular forces using the atom-atom approximation and the potential
      parameters of Nemethy et al. (Nemethy, G.; Pottle, M. S.; Scheraga, H. A. J.
      Phys. Chem. 1983, 87, 1883-1887) reveals the crystallization to be dominated by
      intermolecular interactions between lactose molecules rather than lactose-water
      interactions, suggesting that water of hydration plays a space-filling role in
      the growth process. The simulated crystal shows a tomahawk-like morphology with
      the polar effect of the monoclinic space group P21 correctly reproduced by the
      occurrence of only one of the [010] forms. Confrontation of these results with
      experimental work of our own, involving crystals precipitated from aqueous
      solutions at various degrees of undercooling examined by scanning electron
      microscopy, and that of Visser and Bennema (Visser, R. A.; Bennema, P. Neth. Milk
      Dairy J. 1983, 37,109-137), who assigned faces to a crystal, gives good
      agreement, suggesting the suitability of the force field and atom-atom approaches
      to model the crystallization of organic hydrates.

PMID- 9002475
TI  - Cardiologists broaden use of stents.

PMID- 9002477
TI  - Dog bites recognized as public health problem.

PMID- 9002476
TI  - Biological response modifiers may yield a new class of drugs to treat arthritis.

PMID- 9002478
TI  - From the Centers for Disease Control and Prevention. Update: raccoon rabies
      epizootic--United States, 1996.

PMID- 9002479
TI  - From the Centers for Disease Control and Prevention. Hypothermia-related deaths-
      Vermont, October 1994-February 1996.

PMID- 9002480
TI  - From the Centers for Disease Control and Prevention. Abortion surveillance:
      preliminary data--United States, 1994.

PMID- 9002482
TI  - Genocide and the plight of children in Rwanda.

PMID- 9002483
TI  - Inactivated poliovirus vaccine and vaccine-associated paralytic poliomyelitis.

PMID- 9002484
TI  - Lupuslike reaction associated with minocycline.

PMID- 9002486
TI  - The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS)

PMID- 9002487
TI  - The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS)

PMID- 9002485
TI  - Myositis and rhabdomyolysis associated with concurrent use of simvastatin and
      nefazodone.

PMID- 9002488
TI  - The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS)

PMID- 9002489
TI  - Influence of ethnicity on advance directives and end-of-life decisions.

PMID- 9002490
TI  - Hospital variation in intrapartum use of zidovudine.

PMID- 9002491
TI  - Prostate cancer screening.

PMID- 9002492
TI  - Adverse drug events in hospitalized patients. Excess length of stay, extra costs,
      and attributable mortality.
AB  - OBJECTIVE: To determine the excess length of stay, extra costs, and mortality
      attributable to adverse drug events (ADEs) in hospitalized patients. DESIGN:
      Matched case-control study. SETTING: The LDS Hospital, a tertiary care health
      care institution. PATIENTS: All patients admitted to LDS Hospital from January 1,
      1990, to December 31, 1993, were eligible. Cases were defined as patients with
      ADEs that occurred during hospitalization; controls were selected according to
      matching variables in a stepwise fashion. METHODS: Controls were matched to cases
      on primary discharge diagnosis related group (DRG), age, sex, acuity, and year of
      admission; varying numbers of controls were matched to each case. Matching was
      successful for 71% of the cases, leading to 1580 cases and 20,197 controls. MAIN
      OUTCOME MEASURES: Crude and attributable mortality, crude and attributable length
      of stay, and cost of hospitalization. RESULTS: ADEs complicated 2.43 per 100
      admissions to the LDS Hospital during the study period. The crude mortality rates
      for the cases and matched controls were 3.5% and 1.05%, respectively (P<.001).
      The mean length of hospital stay significantly differed between the cases and
      matched controls (7.69 vs 4.46 days; P<.001) as did the mean cost of
      hospitalization ($10,010 vs $5355; P<.001). The extra length of hospital stay
      attributable to an ADE was 1.74 days (P<.001). The excess cost of hospitalization
      attributable to an ADE was $2013 (P<.001). A linear regression analysis for
      length of stay and cost controlling for all matching variables revealed that the
      occurrence of an ADE was associated with increased length of stay of 1.91 days
      and an increased cost of $2262 (P<.001). In a similar logistic regression
      analysis for mortality, the increased risk of death among patients experiencing
      an ADE was 1.88 (95% confidence interval, 1.54-2.22; P<.001). CONCLUSION: The
      attributable lengths of stay and costs of hospitalization for ADEs are
      substantial. An ADE is associated with a significantly prolonged length of stay,
      increased economic burden, and an almost 2-fold increased risk of death.

PMID- 9002493
TI  - The costs of adverse drug events in hospitalized patients. Adverse Drug Events
      Prevention Study Group.
AB  - OBJECTIVE: To assess the additional resource utilization associated with an
      adverse drug event (ADE). DESIGN: Nested case-control study within a prospective
      cohort study. PARTICIPANTS: The cohort included 4108 admissions to a stratified
      random sample of 11 medical and surgical units in 2 tertiary-care hospitals over
      a 6-month period. Cases were patients with an ADE, and the control for each case
      was the patient on the same unit as the case with the most similar pre-event
      length of stay. MAIN OUTCOME MEASURES: Postevent length of stay and total costs.
      METHODS: Incidents were detected by self-report stimulated by nurses and
      pharmacists and by daily chart review, and were classified as to whether they
      represented ADEs. Information on length of stay and charges was obtained from
      billing data, and costs were estimated by multiplying components of charges times
      hospital-specific ratios of costs to charges. RESULTS: During the study period,
      there were 247 ADEs among 207 admissions. After outliers and multiple episodes
      were excluded, there were 190 ADEs, of which 60 were preventable. In paired
      regression analyses adjusting for multiple factors, including severity,
      comorbidity, and case mix, the additional length of stay associated with an ADE
      was 2.2 days (P=.04), and the increase in cost associated with an ADE was $3244
      (P=.04). For preventable ADEs, the increases were 4.6 days in length of stay
      (P=.03) and $5857 in total cost (P=.07). After adjusting for our sampling
      strategy, the estimated postevent costs attributable to an ADE were $2595 for all
      ADEs and $4685 for preventable ADEs. Based on these costs and data about the
      incidence of ADEs, we estimate that the annual costs attributable to all ADEs and
      preventable ADEs for a 700-bed teaching hospital are $5.6 million and $2.8
      million, respectively. CONCLUSIONS: The substantial costs of ADEs to hospitals
      justify investment in efforts to prevent these events. Moreover, these estimates
      are conservative because they do not include the costs of injuries to patients or
      malpractice costs.

PMID- 9002494
TI  - Factors related to errors in medication prescribing.
AB  - OBJECTIVE: To quantify the type and frequency of identifiable factors associated
      with medication prescribing errors. DESIGN AND SETTING: Systematic evaluation of
      every third prescribing error detected and averted by pharmacists in a 631-bed
      tertiary care teaching hospital between July 1, 1994, and June 30, 1995. Each
      error was concurrently evaluated for the potential to result in adverse patient
      consequences. Each error was retrospectively evaluated by a physician and 2
      pharmacists and a factor likely related to the error was identified.
      PARTICIPANTS: All physicians prescribing medications during the study period and
      all staff pharmacists involved in the routine review of medication orders. MAIN
      OUTCOME MEASURES: Frequency of association of factors likely related to
      medication errors in general and specific to medication classes and prescribing
      services (needed for medical, pediatric, obstetric-gynecologic, surgical, or
      emergency department patients); and potential consequences of errors for negative
      patient outcomes. RESULTS: A total of 2103 errors thought to have potential
      clinical importance were detected during the 1-year study period. The overall
      rate of errors was 3.99 errors per 1000 medication orders, and the error rate
      varied among medication classes and prescribing services. A total of 696 errors
      met study criteria (ie, errors with the potential for adverse patient effects)
      and were evaluated for a likely related factor. The most common specific factors
      associated with errors were decline in renal or hepatic function requiring
      alteration of drug therapy (97 errors, 13.9%), patient history of allergy to the
      same medication class (84 errors, 12.1%), using the wrong drug name, dosage form,
      or abbreviation (total of 79 errors, 11.4%, for both brand name and generic name
      orders), incorrect dosage calculations (77 errors, 11.1%), and atypical or
      unusual and critical dosage frequency considerations (75 errors, 10.8%). The most
      common groups of factors associated with errors were those related to knowledge
      and the application of knowledge regarding drug therapy (209 errors, 30%);
      knowledge and use of knowledge regarding patient factors that affect drug therapy
      (203 errors, 29.2%); use of calculations, decimal points, or unit and rate
      expression factors (122 errors, 17.5%); and nomenclature factors (incorrect drug
      name, dosage form, or abbreviation) (93 errors, 13.4%). CONCLUSIONS: Several
      easily identified factors are associated with a large proportion of medication
      prescribing errors. By improving the focus of organizational, technological, and
      risk management educational and training efforts using the factors commonly
      associated with prescribing errors, risk to patients from adverse drug events
      should be reduced.

PMID- 9002495
TI  - Ischemia during ambulatory monitoring as a prognostic indicator in patients with
      stable coronary artery disease.
AB  - OBJECTIVE: To assess long-term prognostic significance of transient ischemia in
      patients with documented coronary artery disease and stable symptoms and to
      examine the relation between transient ischemia and the site of angiographic
      disease progression following acute cardiac events. DESIGN: Cohort study with a
      mean+/-SD follow-up of 51.5+/-23.8 months. SETTING: Ambulatory patients with
      stable coronary artery disease, assigned to medical therapy. PATIENTS: A total
      221 patients (173 men; mean age, 60.8 years) were recruited. Of the 221 patients,
      101 (45.7%) had single-vessel, 86 (38.9%) had 2-vessel, and 34 (15.4%) had 3
      vessel disease. A total of 135 had a positive exercise test for ischemia, and
      mean+/-SD resting left ventricular ejection fraction (LVEF) was 49.8%+/-11.4%.
      Using conventional criteria, patients were prospectively stratified as low risk
      for continued medical therapy (single-vessel disease, 2-vessel disease with
      negative exercise test, or LVEF> or =40%; n=189 [85.5%]) or high risk for
      continued medical therapy (multivessel disease with ischemia and/or left
      ventricular dysfunction; n=32 [14.5%]). INTERVENTIONS: Ambulatory ST-segment
      monitoring, treadmill exercise testing, radionuclide ventriculography, and
      coronary angiography. MAIN OUTCOME MEASURES: Demographic, clinical, ambulatory
      monitoring, treadmill exercise, and left ventricular function variables as
      independent predictors of acute (cardiac death, myocardial infarction, or
      unstable angina) or all (including revascularization) cardiac events in the
      overall and the low-risk population. RESULTS: None of the clinical or noninvasive
      measures of ischemia were of prognostic significance in the overall or the low
      risk group. The only significant independent predictor of outcome in all patients
      for all events, including revascularization, was the number of diseased vessels
      (X2=13.5 [df=1]; P<.001). Exclusion of vessel disease resulted in conventional
      risk stratification as the most significant predictor of outcome from all events
      in all patients (X2= 10.3 [df= 1]; P=.001). In the low-risk group, the number of
      diseased vessels was the only predictor for all events (X2=4.6; P=.03). For acute
      cardiac events, none of the variables tested were of prognostic significance.
      Based on the frequency of events in the low-risk patients, a 2-fold increase in
      the rate of cardiac events in patients with transient ischemia compared with
      those without transient ischemia during ambulatory monitoring could be excluded
      with greater than 85% power and alpha of .05. Of 30 patients suffering acute
      nonfatal cardiac events during follow-up, angiography was performed in 27,
      revealing significant progression of coronary disease in 24 (88.8%) and the
      development of new significant lesions at sites remote from previously
      significant lesions in 20 (74%) cases. These new lesions were equally likely to
      occur in those with or without transient ischemia at initial assessment.
      CONCLUSIONS: Acute cardiac events in predominantly low-risk stable angina
      patients with confirmed coronary disease are unpredictable, and those more likely
      to suffer such an event cannot be identified by the detection of ambulatory
      ischemia. Acute nonfatal cardiac events result predominantly from the development
      of significant new coronary lesions, not initially severe enough to cause
      ischemia. Patients categorized as high risk for long-term medical therapy have an
      increased rate of cardiac events (mainly revascularization) when compared with
      low-risk patients.

PMID- 9002496
TI  - Effects of acadesine on myocardial infarction, stroke, and death following
      surgery. A meta-analysis of the 5 international randomized trials. The
      Multicenter Study of Perioperative Ischemia (McSPI) Research Group.
AB  - OBJECTIVE: To determine the effects of a purine nucleoside, acadesine, on the
      incidence of fatal and nonfatal cardiovascular and cerebrovascular complications
      following coronary artery bypass graft (CABG) surgery. DATA SOURCES: Individual
      patient data from 5 randomized, placebo-controlled, double-blind clinical trials,
      including 81 international medical centers of the United States, Canada, and
      Europe. STUDY SELECTION: All patients from all clinical trials were included: a
      total of 4043 patients undergoing CABG surgery, evaluable for efficacy, and
      randomized to receive either placebo (n= 2031) or acadesine (0.1 mg x kg(-1) x
      min(-1); n=2012) by intravenous infusion for 7 continuous hours and via the
      cardioplegia solution. DATA EXTRACTION: Individual patient data were collected
      prospectively using standardized forms and methods and double-data entry. A
      general parametric approach and analysis-by-patient meta-analysis were used,
      including both fixed effects and random effects models. Inclusion and exclusion
      criteria, general methodology, and outcome assessment techniques were similar for
      all trials. DATA SYNTHESIS: Acadesine decreased the incidence of the primary
      outcome, perioperative myocardial infarction (MI) by 27% (odds ratio [OR], 0.69;
      95% confidence interval [CI], 0.51-0.95; P=.02), decreased the incidence of
      cardiac death through postoperative day 4 by 50% (OR, 0.52; 95% Cl, 0.27-0.98;
      P=.04), and decreased the incidence of combined outcome (MI, stroke, or cardiac
      death) by 26% (OR, 0.73; 95% Cl, 0.57-0.93; P=.01). The random effects models for
      these outcomes also yielded significant results. The incidence of cerebrovascular
      accident was not significantly reduced by acadesine (OR, 0.69; 95% Cl, 0.44-1.08;
      P=.10). A secondary analysis of cardiac death following MI through postoperative
      day 4 demonstrated that acadesine decreased by 89% the number of deaths from
      13.3% (13 deaths/98 MIs) in the placebo group to 1.4% (1 death/71 MIs) in
      acadesine-treated patients (P=.003). Acadesine also reduced the use of
      ventricular-assistance devices for severe postoperative heart failure by
      approximately one third (P=.05). Finally, regarding safety, the incidence of
      adverse events was similar in the acadesine vs placebo groups, with the exception
      of a transient increase in serum uric acid in the acadesine group. CONCLUSIONS:
      The results of this meta-analysis indicate that in patients undergoing CABG
      surgery, treatment with acadesine before and during surgery can reduce early
      cardiac death, MI, and combined adverse cardiovascular outcomes.

PMID- 9002497
TI  - The National Depressive and Manic-Depressive Association consensus statement on
      the undertreatment of depression.
AB  - OBJECTIVE: A consensus conference on the reasons for the undertreatment of
      depression was organized by the National Depressive and Manic Depressive
      Association (NDMDA) on January 17-18, 1996. The target audience included health
      policymakers, clinicians, patients and their families, and the public at large.
      Six key questions were addressed: (1) Is depression undertreated in the community
      and in the clinic? (2) What is the economic cost to society of depression? (3)
      What have been the efforts in the past to redress undertreatment and how
      successful have they been? (4) What are the reasons for the gap between our
      knowledge of the diagnosis and treatment of depression and actual treatment
      received in this country? (5) What can we do to narrow this gap? (6) What can we
      do immediately to narrow this gap? PARTICIPANTS: Consensus panel members were
      drawn from psychiatry, psychology, family practice, internal medicine, managed
      care and public health, consumers, and the general public. The panelists listened
      to a set of presentations with background papers from experts on diagnosis,
      epidemiology, treatment, and cost of treatment. EVIDENCE: Experts summarized
      relevant data from the world scientific literature on the 6 questions posed for
      the conference. CONSENSUS PROCESS: Panel members discussed openly all material
      presented to them in executive session. Selected panelists prepared first drafts
      of the consensus statements for each question. All of these drafts were read by
      all panelists and were edited and reedited until consensus was achieved.
      CONCLUSIONS: There is overwhelming evidence that individuals with depression are
      being seriously undertreated. Safe, effective, and economical treatments are
      available. The cost to individuals and society of this undertreatment is
      substantial. Long suffering, suicide, occupational impairment, and impairment in
      interpersonal and family relationships exist. Efforts to redress this gap have
      included provider educational programs and public educational programs. Reasons
      for the continuing gap include patient, provider, and health care system factors.
      Patient-based reasons include failure to recognize the symptoms, underestimating
      the severity, limited access, reluctance to see a mental health care specialist
      due to stigma, noncompliance with treatment, and lack of health insurance.
      Provider factors include poor professional school education about depression,
      limited training in interpersonal skills, stigma, inadequate time to evaluate and
      treat depression, failure to consider psychotherapeutic approaches, and
      prescription of inadequate doses of antidepressant medication for inadequate
      durations. Mental health care systems create barriers to receiving optimal
      treatment. Strategies to narrow the gap include enhancing the role of patients
      and families as participants in care and advocates; developing performance
      standards for behavioral health care systems, including incentives for positive
      identification, assessment, and treatment of depression; enhancing educational
      programs for providers and the public; enhancing collaboration among provider
      subtypes (eg, primary care providers and mental health professionals); and
      conducting research on development and testing of new treatments for depression.

PMID- 9002498
TI  - Putting adverse drug events into perspective.

PMID- 9002499
TI  - Can we predict future acute coronary events in patients with stable coronary
      artery disease?

PMID- 9002501
TI  - Xenotransplantation: the heart of the matter.

PMID- 9002502
TI  - Icy complexion of Jupiter's frozen moon.

PMID- 9002500
TI  - Communication patterns of primary care physicians.
AB  - OBJECTIVES: To use audiotape analysis to describe communication patterns in
      primary care, to relate these to ideal relationship types as described in the
      literature, and to explore the patterns' relationships with physician and patient
      characteristics and satisfaction. DESIGN: Description of routine communication in
      primary care based on audiotape analysis and patient and physician exit
      questionnaires. SETTING: A total of 11 ambulatory clinics and private practices.
      PARTICIPANTS: The participants were 127 physicians and 537 patients coping with
      ongoing problems related to disease. MAIN OUTCOMES MEASURES: Roter Interactional
      Analysis System (RIAS) and patient and physician exit satisfaction
      questionnaires. RESULTS: Cluster analysis revealed 5 distinct communication
      patterns: (1) "narrowly biomedical," characterized by closed-ended medical
      questions and biomedical talk occurring in 32% of visits; (2) "expanded
      biomedical," like the restricted pattern but with moderate levels of psychosocial
      discussion occurring in 33% of the visits; (3) "biopsychosocial," reflecting a
      balance of psychosocial and biomedical topics (20% of the visits); (4)
      "psychosocial," characterized by psychosocial exchange (8% of visits); and (5)
      "consumerist," characterized primarily by patient questions and physician
      information giving (8% of visits). Biomedically focused visits were used more
      often with more sick, older, and lower income patients by younger, male
      physicians. Physician satisfaction was lowest in the narrowly biomedical pattern
      and highest in the consumerist pattern, while patient satisfaction was highest in
      the psychosocial pattern. CONCLUSIONS: Primary care communication patterns range
      from narrowly biomedical to consumerist patterns and parallel the ideal forms of
      patient-physician relationships described in the literature.

PMID- 9002503
TI  - Human genome centre receives a leg-up.

PMID- 9002504
TI  - Change for Europe's science committees.

PMID- 9002505
TI  - Britain plays it cautious on animal-human transplants.

PMID- 9002506
TI  - Pros and cons of foreign genes in crops.

PMID- 9002507
TI  - Pros and cons of foreign genes in crops.

PMID- 9002508
TI  - Too quiet to hear a whisper.

PMID- 9002509
TI  - Palaeoanthropology. The oldest whodunnit in the world.

PMID- 9002510
TI  - Pirated genes in Kaposi's sarcoma.

PMID- 9002511
TI  - Thalidomide's chirality.

PMID- 9002512
TI  - Fugu genome is not a good mammalian model.

PMID- 9002513
TI  - Sound alters visual motion perception.

PMID- 9002514
TI  - A tension-based theory of morphogenesis and compact wiring in the central nervous
      system.
AB  - Many structural features of the mammalian central nervous system can be explained
      by a morphogenetic mechanism that involves mechanical tension along axons,
      dendrites and glial processes. In the cerebral cortex, for example, tension along
      axons in the white matter can explain how and why the cortex folds in a
      characteristic species-specific pattern. In the cerebellum, tension along
      parallel fibres can explain why the cortex is highly elongated but folded like an
      accordion. By keeping the aggregate length of axonal and dendritic wiring low,
      tension should contribute to the compactness of neural circuitry throughout the
      adult brain.

PMID- 9002515
TI  - Stochastic resonance in non-dynamical systems without response thresholds.
AB  - The addition of noise to a system can sometimes improve its ability to transfer
      information reliably. This phenomenon--known as stochastic resonance--was
      originally proposed to account for periodicity in the Earth's ice ages, but has
      now been shown to occur in many systems in physics and biology. Recent
      experimental and theoretical work has shown that the simplest system exhibiting
      'stochastic resonance' consists of nothing more than signal and noise with a
      threshold-triggered device (when the signal plus noise exceeds the threshold, the
      system responds momentarily, then relaxes to equilibrium to await the next
      triggering event). Here we introduce a class of non-dynamical and threshold-free
      systems that also exhibit stochastic resonance. We present and analyse a general
      mathematical model for such systems, in which a sequence of pulses is generated
      randomly with a probability (per unit time) that depends exponentially on an
      input. When this input is a sine-wave masked by additive noise, we observe an
      increase in the output signal-to-noise ratio as the level of noise increases.
      This result shows that stochastic resonance can occur in a broad class of
      thermally driven physico-chemical systems, such as semiconductor p-n junctions,
      mesoscopic electronic devices and voltage-dependent ion channels, in which
      reaction rates are controlled by activation barriers.

PMID- 9002516
TI  - 2.5-million-year-old stone tools from Gona, Ethiopia.
AB  - The Oldowan Stone tool industry was named for 1.8-million-year-old (Myr)
      artefacts found near the bottom of Olduvai Gorge, Tanzania. Subsequent
      archaeological research in the Omo (Ethiopia) and Turkana (Kenya) also yielded
      stone tools dated to 2.3 Myr. Palaeoanthropological investigations in the Hadar
      region of the Awash Valley of Ethiopia, revealed Oldowan assemblages in the
      adjacent Gona River drainage. We conducted field work in the Gona study area of
      Ethiopia between 1992 and 1994 which resulted in additional archaeological
      discoveries as well as radioisotopic age control and a magnetic polarity
      stratigraphy of the Gona sequence. These occurrences are now securely dated
      between 2.6-2.5 Myr. The stone tools are thus the oldest known artefacts from
      anywhere in the world. The artefacts show surprisingly sophisticated control of
      stone fracture mechanics, equivalent to much younger Oldowan assemblages of Early
      Pleistocene age. This indicates an unexpectedly long period of technological
      stasis in the Oldowan.

PMID- 9002517
TI  - Circumsporozoite protein is required for development of malaria sporozoites in
      mosquitoes.
AB  - Malaria parasites undergo a sporogonic cycle in the mosquito vector. Sporozoites,
      the form of the parasite injected into the host during a bloodmeal, develop
      inside oocysts in the insect midgut, then migrate to and eventually invade the
      salivary glands. The circumsporozoite protein (CS), one of the major proteins
      synthesized by salivary gland sporozoites, is a surface-associated molecule which
      is important in sporozoite infectivity to the host. Here, by gene targeting, we
      created Plasmodium berghei lines in which the single-copy CS gene was disrupted.
      The CS(-) and wild-type parasites produced similar numbers of oocysts of
      comparable size in the mosquito midgut. In the CS(-) oocysts, however, sporozoite
      formation was profoundly inhibited. CS therefore appears to have a pleiotropic
      role and to be vital for malaria parasites in both the vector and the host: in
      mosquitoes, CS is essential for sporozoite development within oocysts, and in the
      vertebrate host it promotes sporozoite attachment to hepatocytes.

PMID- 9002518
TI  - Cleavage of syntaxin prevents G-protein regulation of presynaptic calcium
      channels.
AB  - Neurotransmitter release into the synapse is stimulated by calcium influx through
      ion channels that are closely associated with the transmitter release sites. This
      link may involve the membrane protein syntaxin, which is known to be associated
      with the release sites and to bind to the calcium channels. There is evidence
      that presynaptic calcium channels are downregulated by second messenger pathways
      involving G proteins. Here we use the patch-clamp technique to test whether
      calcium current is regulated by G proteins in a vertebrate presynaptic nerve
      terminal, and whether this regulation is affected by the linkage to syntaxin. The
      calcium current in the nerve terminal showed typical G-protein-mediated changes
      in amplitude and activation kinetics which were reversed by a preceding
      depolarization. These effects of the G protein were virtually eliminated if
      syntaxin was first cleaved with botulinum toxin C1. Our findings indicate that
      this sensitivity of the current to modulation by G proteins requires the
      association of the presynaptic calcium channel with elements of the transmitter
      release site, which may ensure that channels tethered at release sites are
      preferentially regulated by the G-protein second messenger pathway.

PMID- 9002519
TI  - Regulation by insulin of a unique neuronal Ca2+ pool and of neuropeptide
      secretion.
AB  - The insulin receptor is a tyrosine kinase receptor that is found in mammalian
      brain and at high concentrations in the bag cell neurons of Aplysia. We show here
      that insulin causes an acute rise in intracellular Ca2+ concentration ([Ca2+]i)
      in these neurons and triggers release of neuropeptide. The insulin-sensitive
      intracellular Ca2+ pool differs pharmacologically from previously described Ca2+
      stores that are sensitive to inositol trisphosphate and from mitochondrial Ca2+
      stores. Insulin, but not thapsigargin, stimulates Ca2+ release at the distal tips
      of neurites, the presumed site of neuropeptide secretion. The effects of insulin
      on intracellular Ca2+ release and neuropeptide secretion occur without triggering
      spontaneous action potentials. The insulin-sensitive rise in [Ca2+]i moves into
      the distal tips of neurites after exposure to a cyclic AMP analogue, a treatment
      that causes a similar translocation of neuronal vesicles. Our data indicate that
      Ca2+ release from a distinct intracellular pool associated with secretory
      vesicles may contribute to secretion of neuropeptide in the absence of neuronal
      discharge.

PMID- 9002520
TI  - Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor
      linked to cell proliferation.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV, also known as human herpesvirus 8,
      or HHV 8) is a virus that is consistently present in Kaposi's sarcoma and in
      primary-effusion (body-cavity-based) lymphomas, malignancies that occur
      frequently, but not exclusively, in AIDS patients. KSHV is a gamma herpesvirus
      with homology to herpesvirus Saimiri and Epstein-Barr virus, both of which can
      transform lymphocytes. Cloning of a KSHV genome fragment revealed the presence of
      an open reading frame encoding a putative G-protein-coupled receptor that is
      homologous to a G-protein-coupled receptor encoded by herpesvirus Saimiri and to
      human interleukin-8 receptors. Here we show that the KSHV G-protein-coupled
      receptor is a bona fide signalling receptor which has constitutive (agonist
      independent) activity in the phosphoinositide-inositoltrisphosphate-protein
      kinase C pathway. Furthermore, the KSHV G-protein-coupled receptor stimulates
      cellular proliferation, making it a candidate viral oncogene.

PMID- 9002521
TI  - Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95
      and CD3.
AB  - Distinct and evolutionarily conserved signal transduction cascades mediate
      survival or death in response to developmental and environmental cues. The stress
      activated protein kinases, or Jun N-terminal kinases (SAPKs/JNKs), are activated
      in response to a variety of cellular stresses such as changes in osmolarity and
      metabolism, DNA damage, heat shock, ischaemia, or inflammatory cytokines. Sek1
      (JNKK/MKK4) is a direct activator of SAPKs/JNKs in response to environmental
      stresses or mitogenic factors. Here we investigate the role of Sek1 in
      development and apoptosis by deleting sek1 in embryonic stem (ES) cells by
      homologous recombination. We provide genetic evidence that different stresses
      utilize distinct signalling pathways for SAPK/JNK activation. sek1(-/-) rag2(-/-)
      chimaeric mice have normal numbers of mature T cells but fewer immature CD4+CD8+
      thymocytes. The sek1 mutation did not affect the induction of apoptosis in
      response to environmental stresses in ES and T cells: instead, sek1 protected
      thymocytes from CD95 (Fas)- and CD3-mediated apoptosis. These data indicate that
      SEK1 mediates survival signals in T-cell development.

PMID- 9002522
TI  - Bcl-x(L) forms an ion channel in synthetic lipid membranes.
AB  - Bcl-2-related proteins are critical regulators of cell survival that are
      localized to the outer mitochondrial, outer nuclear and endoplasmic reticulum
      membranes. Despite their physiological importance, the biochemical function of
      Bcl-2-related proteins has remained elusive. The three-dimensional structure of
      Bcl-xL, an inhibitor of apoptosis, was recently shown to be similar to the
      structures of the pore-forming domains of bacterial toxins. A key feature of
      these pore-forming domains is the ability to form ion channels in biological
      membranes. Here we demonstrate that Bcl-xL shares this functional feature. Like
      the bacterial toxins, Bcl-xL can insert into either synthetic lipid vesicles or
      planar lipid bilayers and form an ion-conducting channel. This channel is pH
      sensitive and becomes cation-selective at physiological pH. The ion-conducting
      channel(s) formed by Bcl-xL display multiple conductance states that have
      identical ion selectivity. Together, these data suggest that Bcl-xL may maintain
      cell survival by regulating the permeability of the intracellular membranes to
      which it is distributed.

PMID- 9002523
TI  - The C-terminal domain of RNA polymerase II couples mRNA processing to
      transcription.
AB  - Messenger RNA is produced by RNA polymerase II (pol II) transcription, followed
      by processing of the primary transcript. Transcription, splicing and cleavage
      polyadenylation can occur independently in vitro, but we demonstrate here that
      these processes are intimately linked in vivo. We show that the carboxy-terminal
      domain (CTD) of the pol II large subunit is required for efficient RNA
      processing. Splicing, processing of the 3' end and termination of transcription
      downstream of the poly(A) site, are all inhibited by truncation of the CTD. We
      found that the cleavage-polyadenylation factors CPSF and CstF specifically bound
      to CTD affinity columns and copurified with pol II in a high-molecular-mass
      complex. Our demonstration of an association between the CTD and 3'-processing
      factors, considered together with reports of a similar interaction with splicing
      factors, suggests that an mRNA 'factory' exists which carries out coupled
      transcription, splicing and cleavage-polyadenylation of mRNA precursors.

PMID- 9002524
TI  - Structure of the conserved GTPase domain of the signal recognition particle.
AB  - The signal-recognition particle (SRP) and its receptor (SR) function in the co
      translational targeting of nascent protein-ribosome complexes to the membrane
      translocation apparatus. The SRP protein subunit (termed Ffh in bacteria) that
      recognizes the signal sequence of nascent polypeptides is a GTPase, as is the SR
      alpha subunit (termed FtsY). Ffh and FtsY interact directly, each stimulating the
      GTP hydrolysis activity of the other. The sequence of Ffh suggests three domains:
      an amino-terminal N domain of unknown function, a central GTPase G domain, and a
      methionine-rich M domain that binds both SRP RNA and signal peptides. Sequence
      conservation suggests that structurally similar N and G domains are present in
      FtsY. Here we report the structure of the nucleotide-free form of the NG fragment
      of Ffh. Consistent with a role for apo Ffh in protein targeting, the side chains
      of the empty active-site pocket form a tight network of interactions which may
      stabilize the nucleotide-free protein. The structural relationship between the
      two domains suggests that the N domain senses or controls the nucleotide
      occupancy of the GTPase domain. A structural subdomain unique to these
      evolutionarily conserved GTPases constitutes them as a distinct subfamily in the
      GTPase superfamily.

PMID- 9002525
TI  - Crystal structure of the NG domain from the signal-recognition particle receptor
      FtsY.
AB  - Newly synthesized proteins destined either for secretion or incorporation into
      membranes are targeted to the membrane translocation machinery by a ubiquitous
      system consisting of a signal-recognition particle (SRP) and its receptor. Both
      the SRP receptor and the protein within the SRP that binds the signal sequence
      contain GTPases. These two proteins, together with the RNA component of the SRP,
      form a complex and thereby regulate each other's GTPase activity. Here we report
      the structure of the GTPase-containing portion of FtsY, the functional homologue
      of the SRP receptor of Escherichia coli, at 2.2 A resolution without bound
      nucleotide. This so-called NG domain displays similarities to the Ras-related
      GTPases, as well as features unique to the SRP-type GTPases, such as a separate
      amino-terminal domain, an insertion within the p21ras (Ras) effector domain, and
      a wide-open GTP-binding region. The structure explains the low affinity of FtsY
      for GTP, and suggests rearrangements that may occur on nucleotide binding. It
      also identifies regions potentially involved in the transmission of signals
      between domains and in interactions with regulatory proteins.

PMID- 9002526
TI  - Endothelins in the normal and diseased kidney.
AB  - Endothelin-1 (ET-1) is a 21-amino acid peptide that potently modulates renal
      function. ET-1 is produced by, and binds to, most renal cell types. ET-1 exerts a
      wide range of biologic effects in the kidney, including constriction of most
      renal vessels, mesangial cell contraction, inhibition of sodium and water
      reabsorption by the nephron, enhancement of glomerular cell proliferation, and
      stimulation of extracellular matrix accumulation. ET-1 functions primarily as an
      autocrine or paracrine factor; its renal effects must be viewed in the context of
      its local production and actions. This is particularly important when comparing
      ET-1 biology in the nephron, where it promotes relative hypotension through
      increased salt and water excretion, with ET-1 effects in the vasculature, where
      it promotes relative hypertension through vasoconstriction. Numerous studies
      indicate that ET-1 is involved in the pathogenesis of a broad spectrum of renal
      diseases. These include those characterized by excessive renal vascular
      resistance, such as ischemic renal failure, cyclosporine (CyA) nephrotoxicity,
      radiocontrast nephropathy, endotoxemia, rhabdomyolysis, acute liver rejection,
      and others. ET-1 appears to play a role in cell proliferation in the setting of
      inflammatory glomerulonephritides. The peptide also may mediate, at least in
      part, excessive extracellular matrix accumulation and fibrosis occurring in
      chronic renal failure, diabetes mellitus, and other disorders. Deranged ET-1
      production in the nephron may cause inappropriate sodium and water retention,
      thereby contributing to the development and/or maintenance of hypertension.
      Finally, impaired renal clearance of ET-1 may cause hypertension in patients with
      end-stage renal disease. Many ET-1 antagonists have been developed; however,
      their clinical usefulness has not yet been determined. Despite this, these agents
      hold great promise for the treatment of renal diseases; it is hoped that the next
      decade will witness their introduction into clinical practice.

PMID- 9002527
TI  - Characterization of proteinuria in primary glomerulonephritides. SDS-PAGE
      patterns: clinical significance and prognostic value of low molecular weight
      ("tubular") proteins.
AB  - In 145 patients with focal segmental glomerulosclerosis (43), membranous
      glomerulonephritis (72), and membranoproliferative glomerulonephritis (30), 71%
      with normal renal function (NRF) and 63% with nephrotic syndrome (NS), the
      proteinuria was evaluated by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and classified into four main patterns: physiological
      (termed 70 kd), pure glomerular (150 kd), mixed with low molecular weight (LMW)
      proteins as low as 23 kd (23 kd), and mixed with very LMW proteins (20 to 10 kd;
      termed 10 kd). The relative frequencies were 70 kd, 0.7%; 150 kd, 1.4%; 23 kd,
      61%; and 10 kd, 37%. Therefore, only the two patterns characterized by LMW
      ("tubular") proteins were compared to determine whether they have different
      clinical and prognostic significance. The serum creatinine (sCr) values (P <
      0.0001), the degrees of proteinuria (P = 0.007), and the tubulointerstitial
      damage (P = 0.015) were significantly different in the two subgroups of patients
      with 23-kd and 10-kd LMW proteinuria; the difference for tubulointerstitial
      damage was at the limit of statistical significance after Bonferroni correction.
      In 82 patients with NRF at entry (sCr, 1.00 +/- 0.22 mg/dL; range, 0.6 to 1.4
      mg/dL) and a follow-up of 46 +/- 22 months (range, 12 to 84 months), the
      predictive value of the 23-kd and 10-kd SDS-PAGE patterns on functional outcome
      (chronic renal failure [CRF] or clinical remission) was evaluated. A total of
      12.5% of 64 patients with mixed 23-kd proteinuria and 50% of 18 patients with
      mixed 10-kd proteinuria developed CRF. At this time, the difference between the
      survival curves was highly significant (P = 0.0001), as it also was after
      correction for NS (P = 0.0002). When the statistical analysis was limited to 69
      patients with sCr < or = 1.2 mg/dL, the difference was still highly significant
      (P = 0.0016), as after correction for NS (P = 0.0064). Clinical remission
      developed in 30% of 64 patients with 23-kd proteinuria and in 33% of 18 patients
      with 10-kd proteinuria; this difference was not significant. In a retrospective
      analysis of 20 patients (13 focal segmental glomerulosclerosis and seven
      membranous glomerulonephritis; 10 with the 23-kd pattern and 10 with the 10-kd
      pattern) treated with steroids alone or with steroids and cyclophosphamide, 80%
      of the patients with the 23-kd pattern and 30% of the patients with the 10-kd
      pattern were responsive to treatment (P = 0.025). The SDS-PAGE patterns of 54
      patients with NRF at entry were again evaluated after 48 +/- 22 months: 11
      patients who developed clinical remission had changed from a prevalent (91%) 23
      kd pattern to a prevalent physiological (55%) or glomerular (36%) pattern; eight
      patients who had developed CRF showed an increase from 37% to 100% of the 10-kd
      pattern. In 35 patients with normal and stable renal function (sCr from 1.08 +/-
      0.20 mg/dL to 1.06 +/- 0.19 mg/dL) who had persistent proteinuria (20 patients)
      or NS (15 patients), the rate of the 10-kd pattern increased from 6% to 46% (72%
      in persistent NS), suggesting an impairment of tubular protein reabsorptive
      function even without a concomitant impairment of glomerular filtration rate, a
      phenomenon that can be hypothetically attributed to tubular toxicity of
      persistent proteinuria. The characterization of proteinuria by SDS-PAGE in
      primary progressive glomerulonephritis is a useful clinical tool: it can be used
      to identify the main pathophysiologic determinants of excretion of LMW proteins
      and it has a predictive value on CRF outcome in patients with NRF, reducing the
      unpredictability of clinical evolution. In focal segmental glomerulosclerosis and
      membranous glomerulonephritis, it seems to be of predictive value on
      responsiveness to therapy; monitoring the SDS-PAGE patterns over time may give
      some insights into the relationship between the persistent protein loss and the
      progression of the disease.

PMID- 9002528
TI  - A vertical (pseudodominant) pattern of inheritance in the autosomal recessive
      disease primary hyperoxaluria type 1: lack of relationship between genotype,
      enzymic phenotype, and disease severity.
AB  - Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused
      by a deficiency of alanine:glyoxylate aminotransferase (encoded by the AGXT
      gene). Primary hyperoxaluria type 1 is characterized by the elevated urinary
      excretion of oxalate and glycolate, and the deposition of insoluble calcium
      oxalate in the renal parenchyma and urinary tract. In the present study, we
      investigated an unusual family containing four affected individuals in two
      different generations. Based on our genetic, enzymic, metabolic, and clinical
      analyses, we have come to the following conclusions. First, although the pattern
      of inheritance of PH1 is usually horizontal (ie, all patients in the same
      generation), as expected for an autosomal recessive disease, it can sometimes
      show a vertical (pseudodominant) pattern of inheritance (ie, patients in more
      than one generation) due to the segregation within a family of three, rather than
      two, mutant AGXT alleles. Second, affected members of such a family can manifest
      very different clinical phenotypes both within and between generations. Although
      the clinical differences between generations might be at least partly due to
      differences in AGXT genotype, differences can equally occur within the same
      generation in individuals who possess the same AGXT genotype. Finally,
      individuals with PH1 at the level of the AGXT genotype might remain asymptomatic
      and undiagnosed for many years. The consequences of these findings for the
      clinical management and genetic counseling of families with PH1 are profound and
      wide-ranging.

PMID- 9002529
TI  - Sodium-lithium countertransport is associated with insulin resistance and urinary
      albumin excretion in young African-Americans.
AB  - Increased activity of the sodium transporter, sodium-lithium countertransport
      (SLC), is reported in hypertensive white patients with evidence of cardiac and
      renal injury. The purpose of this study was to determine whether increased SLC
      activity detects risk for nephropathy or vascular disease in nondiabetic, young
      adult African-Americans. We examined 85 African-Americans aged 25 to 33 years
      with measurement of blood pressure, an oral glucose tolerance test to measure
      insulin response to glucose challenge, and an insulin clamp for insulin
      sensitivity (M). Fasting plasma lipids were measured, and the Vmax and Km for Na+
      were assayed on red blood cells. Urinary albumin excretion (UAE) was measured on
      timed collections. There was a statistically significant correlation of the Vmax
      for SLC with M (r = -0.26, P = 0.02) and with UAE (r = 0.25, P = 0.02). The Km
      for Na+ to activate SLC was also elevated in the subgroup of subjects with
      elevated Vmax of SLC. There was no significant correlation of SLC with blood
      pressure in bivariate analysis. Step-wise multiple linear regression analysis of
      all variables on the Vmax SLC demonstrated that plasma triglyceride, UAE, body
      mass index, systolic blood pressure, M, and fasting insulin were step-wise
      selected into the linear regression model (F-ratio = 3.2, df = 77, R = 0.46, P <
      0.009). In this young adult African-American population, elevated SLC activity is
      detected in association with metabolic and lipid alterations typical of insulin
      resistance. Elevated SLC activity is also associated with higher rates of UAE,
      suggesting possible evidence of early renal injury.

PMID- 9002530
TI  - The role of abdominal adiposity and insulin resistance in dyslipidemia of chronic
      renal failure.
AB  - The atherogenic profile of high triglyceride, reduced high-density lipoprotein
      (HDL) cholesterol, and small low-density lipoprotein particle size found in
      patients on chronic hemodialysis is known to be associated with insulin
      resistance and abdominal obesity in the general population. To assess the
      influence of insulin resistance and abdominal adiposity on the lipid profile in
      subjects on hemodialysis, intravenous glucose tolerance test and dual-energy x
      ray absorptiometry were performed in 26 nondiabetic subjects on hemodialysis and
      compared with 22 nondiabetic control subjects matched for age, sex, and body mass
      index. Subjects on hemodialysis were found to have higher triglyceride (133 mg/dL
      [95% confidence interval, 115 to 159 mg/dL] v 97 mg/dL [95% confidence interval,
      80 to 124 mg/dL]; P < 0.05), lower HDL cholesterol (36 +/- 3 mg/dL v 51 +/- 4
      mg/dL [mean +/- SEM]; P < 0.01), enhanced insulin response to glucose (2.72 +/-
      0.28 mUL(-1) min per mg dL(-1) v 1.67 +/- 0.22 mUL(-1) min per mg dL(-1); P <
      0.01), and reduced sensitivity to the action of insulin (2.24 min(-1) per mUL(-1)
      min [95% confidence interval, 1.86 to 2.75 min(-1) per mUL(-1) min] v 4.17 min(
      1) mUL(-1) min [95% confidence interval, 2.95 to 5.9 min(-1) per mUL(-1) min]; P
      < 0.01) than the control subjects. Abdominal adiposity measured by dual-energy x
      ray absorptiometry (2,004 +/- 210 g v 2,163 +/- 198 g [mean +/- SEM]; P = NS) and
      percentage of body fat distributed to the abdomen (10.5% +/- 0.3% v 9.7% +/- 0.5%
      [mean +/- SEM]; P = NS) did not differ between the two groups. Subjects on
      hemodialysis were insulin resistant, but unlike control subjects, their lipid
      profile was not predicted by their insulin sensitivity. Abdominal adiposity was
      associated with a deteriorating lipid profile and insulin resistance in subjects
      on hemodialysis, as it was in control subjects. The presence of renal failure
      resulted in additional insulin resistance and a higher triglyceride level in the
      leaner subjects on hemodialysis compared with control subjects with similar
      levels of abdominal fat. In the more obese subjects, insulin sensitivity and
      triglyceride level did not differ between the two groups of subjects, although
      HDL cholesterol level remained low in subjects on hemodialysis. In conclusion,
      insulin resistance in subjects on hemodialysis did not directly account for their
      abnormal lipid profile. The negative impact of abdominal adiposity on the
      metabolic profile was preserved in subjects on hemodialysis, but the presence of
      renal failure itself resulted in insulin resistance in the leaner subjects and
      dyslipidemia in all subjects on hemodialysis compared with control subjects of
      comparable abdominal adiposity.

PMID- 9002532
TI  - Induction of creatininase activity in chronic renal failure: timing of creatinine
      degradation and effect of antibiotics.
AB  - Creatinine degradation was prospectively studied in four healthy subjects and 35
      patients with varying degrees of chronic renal failure by measuring creatininase
      activity in stool isolates. Patients were subdivided into those with serum
      creatinine above and below 6 mg/dL. Creatinine degradation in the former group of
      patients who had not taken antibiotics in the previous 3 months was significantly
      greater than the latter (64% v 26%; P < 0.001), which was similar to healthy
      controls. This degradation was abolished when antibiotics were added directly to
      the patient's stool during incubation (P < 0.002). In a subset of five patients,
      duodenal intubation demonstrated small bowel bacterial overgrowth associated with
      high concentrations of toxic methylamines generated there from and increased
      stool creatinine consumption. We conclude that retained creatinine in advanced
      chronic renal failure induces bacterial creatininase activity throughout the
      bowel, causing creatinine degradation and subsequent potential loss of creatinine
      to the creatinine pool. The modifying effects of antibiotics on creatinine
      degradation has important clinical implications for the interpretation of serum
      creatinine measurements in renal failure.

PMID- 9002533
TI  - Dialysis-induced serum factors inhibit adherence of monocytes and granulocytes to
      adult human endothelial cells.
AB  - In patients on hemodialysis, the sequences of events required for adhesion
      molecule-mediated adherence of monocytes and granulocytes to endothelial cells
      are pathophysiologically disrupted because activation of the cells with
      subsequent alterations in adhesion molecule phenotypes takes place in the
      extracorporeal circuit far away from the respective endothelial cell ligand. As a
      consequence, the host defense to infections may be affected. We analyzed the
      expression of CD62L and CD11b/CD18 on monocytes and granulocytes and the
      adherence of these cells, collected before, during, and after cuprophan
      hemodialysis, to resting and interleukin-1 beta (IL-1 beta)-stimulated adult
      human saphenous vein endothelial cells (HSVECs). Monocytes collected before
      dialysis adhered more avidly to HSVECs than did granulocytes. Adherence of both
      cell types increased to IL-1 beta-stimulated HSVECs (P < 0.05). Granulocytes
      obtained at 180 minutes adhered less to resting HSVECs than granulocytes
      harvested before hemodialysis (P < 0.05), despite an increase in CD11b/CD18
      expression. To study if serum factors inhibiting adherence accumulate during
      hemodialysis, we incubated leukocytes harvested before hemodialysis in the same
      patients' serum collected before, during, and after dialysis. Serum collected at
      180 minutes of cuprophan hemodialysis exerted inhibitory effects on both monocyte
      and granulocyte adhesion to HSVECs (P < 0.05). By contrast, serum collected
      during polysulfone hemodialysis of the same patients did not have any significant
      impact on the adherence of inflammatory cells to HSVECs. These findings
      contribute to an increased understanding of the factors involved in the impaired
      immune response observed in dialysis patients.

PMID- 9002531
TI  - Poly[allylamine hydrochloride] (RenaGel): a noncalcemic phosphate binder for the
      treatment of hyperphosphatemia in chronic renal failure.
AB  - Dietary phosphate restriction and the oral administration of calcium and aluminum
      salts have been the principal means of controlling hyperphosphatemia in
      individuals with end-stage renal disease over the past decade. Although
      relatively well-tolerated, a large fraction of patients treated with calcium
      develop hypercalcemia, particularly when administered concurrently with
      calcitriol, despite a lowering of the dialysate calcium concentration. We
      evaluated the efficacy of cross-linked poly[allylamine hydrochloride] (RenaGel;
      Geltex Pharmaceuticals, Waltham, MA), a nonabsorbable calcium- and aluminum-free
      phosphate binder, in a randomized, placebo-controlled, double-blind trial of 36
      maintenance hemodialysis patients followed over an 8-week period. RenaGel was
      found to be as effective as calcium carbonate or acetate as a phosphate binder.
      The reduction in serum phosphorus was significantly greater after 2 weeks of
      treatment with RenaGel (6.6 +/- 2.1 mg/dL to 5.4 +/- 1.5 mg/dL) compared with
      placebo (7.0 +/- 2.1 mg/dL to 7.2 +/- 2.4 mg/dL; P = 0.037). There was no
      significant change in serum calcium concentration in either treatment group. The
      total serum cholesterol and low-density lipoprotein cholesterol fraction were
      significantly reduced in RenaGel-treated patients compared with placebo-treated
      patients (P = 0.013 and P = 0.003, respectively) without a concomitant reduction
      in high-density lipoprotein cholesterol (P = 0.93). There was no difference among
      recipients of RenaGel and placebo in terms of adverse events. RenaGel is a safe
      and effective alternative to oral calcium for the management of hyperphosphatemia
      in end-stage renal disease.

PMID- 9002534
TI  - Eradication of Helicobacter pylori in patients with end-stage renal disease under
      dialysis treatment.
AB  - The efficacy and safety of combination therapy with amoxicillin, lansoprazole,
      and plaunotol for the eradication of Helicobacter pylori in patients on dialysis
      were evaluated. The study subjects comprised 15 dialysis patients in whom H
      pylori had been found in the gastric mucosa. The patients were given 500 mg
      amoxicillin once a day for 3 weeks, 30 mg lansoprazole once a day for 8 weeks,
      and 80 mg plaunotol three times a day for 24 weeks. Endoscopy was performed on
      entry and at 4 and 24 weeks after cessation of amoxicillin. The concentrations of
      serum gastrin and gastric juice ammonia also were measured. Fourteen patients
      completed the treatment protocol, one having dropped out because of nausea and
      diarrhea. H pylori was eradicated in 11 of the 14 patients 4 weeks after the end
      of amoxicillin therapy (eradication rate, 78.6%). All but one patient was free of
      H pylori 24 weeks after the amoxicillin was discontinued. Patients who became
      negative for H pylori had significantly decreased serum gastrin and gastric juice
      ammonia concentrations. Our findings indicate that a combination of amoxicillin,
      lansoprazole, and plaunotol can be used to eradicate H pylori in patients on
      dialysis.

PMID- 9002535
TI  - Xanthomonas maltophilia peritonitis in uremic patients receiving continuous
      ambulatory peritoneal dialysis.
AB  - Xanthomonas maltophilia peritonitis has been only occasionally reported in
      patients receiving continuous ambulatory peritoneal dialysis. We present a series
      of six cases of peritonitis caused by such bacteria, accounting for 1.5% of all
      peritonitis episodes encountered in our renal unit over the past 5 years. Recent
      bacterial peritonitis treated with broad-spectrum antibiotics was the major risk
      factor, and the outcome was poor with medical treatment alone. Secondary
      peritonitis, especially fungal, was common and probably related to the prolonged
      course of antibiotics. All patients eventually required removal of the catheter,
      either because the effluent failed to clear up or because of secondary
      peritonitis. We suggest that X maltophilia peritonitis be treated with double
      antibiotics as soon as it is diagnosed. To prevent the development of
      superimposed infection after prolonged administration of antibiotics, the
      Tenckhoff catheter should be removed if the peritonitis fails to respond to a
      short course of antibiotics.

PMID- 9002536
TI  - Outcome of patients with antineutrophil cytoplasmic autoantibody-associated
      vasculitis following cadaveric kidney transplantation.
AB  - In this retrospective study, we report on the progress of eight patients with
      biopsy-proven systemic vasculitis following cadaveric renal transplantation.
      Extrarenal manifestations associated with antineutrophil cytoplasmic
      autoantibodies (ANCAs) were present in all but one case. All the patients were on
      cyclosporine A-based immunosuppression, and none of them had active disease at
      transplantation. The mean time from the last episode of vasculitis to
      transplantation was 46 months (range, 10 to 132 months). On the day of
      transplantation, all but one patient had detectable ANCAs, which ranged from
      1:100 to 1:2,000 (perinuclear ANCAs [P-ANCAs], four patients; cytoplasmic ANCAs
      [C-ANCAs], three patients). There were three patients with Wegener's
      granulomatosis, none of whom relapsed. Of those patients with microscopic
      polyangiitis (P-ANCAs, three patients; C-ANCAs, two patients), only one presented
      with relapse episodes after transplantation; the episodes involved the lungs and
      the kidney graft, and were successfully treated by methylprednisolone pulses.
      This patient had the highest ANCA titer before (1:2,000) and after (up to
      1:10,000) grafting, and received no immunosuppression prior to transplantation
      since vasculitis was diagnosed after she had developed end-stage renal failure.
      This study shows that a relapse of ANCA-associated vasculitis following
      successful cadaveric renal transplantation occurs infrequently in the
      cyclosporine A era (ie, 12%), despite the persistence of circulating ANCAs in
      these patients at the time of transplantation, and even afterward in some cases.

PMID- 9002537
TI  - Severe hyperphosphatemia following phosphate administration for bowel preparation
      in patients with renal failure: two cases and a review of the literature.
AB  - Two cases of severe hyperphosphatemia following phosphate bowel preparation are
      described and a review of the literature is presented. Impairment of renal
      function appears to be a risk factor in those patients without primary bowel
      pathology. One of our patients died, and the mortality rate combining our cases
      with all other reported cases is 33%. Repeated doses of phosphate bowel
      preparations/purgatives can be dangerous in patients with renal impairment.

PMID- 9002540
TI  - Membranous lupus nephritis with antineutrophil cytoplasmic antibody-associated
      segmental necrotizing and crescentic glomerulonephritis.
AB  - Focal segmental necrotizing and crescentic lupus nephritis accompanied by
      perinuclear antineutrophil cytoplasmic antibody (P-ANCA) seropositivity is an
      unusual occurrence. We report the first biopsy-documented cases of membranous
      lupus nephritis class V with associated "pauci-immune" segmental necrotizing
      glomerulonephritis and P-ANCA seropositivity. The absence of subendothelial
      electron-dense deposits favored a manifestation of superimposed ANCA-associated
      glomerulonephritis rather than class III lupus nephritis. The pathogenetic
      implications of this association are explored.

PMID- 9002538
TI  - Hypokalemic metabolic alkalosis with hypomagnesuric hypermagnesemia and severe
      hypocalciuria: a new syndrome?
AB  - Bartter's and Gitelman's syndromes are characterized by hypokalemia, urinary
      potassium wasting, elevated plasma renin activity and aldosterone levels,
      normotension, and prostaglandinuria. They differ in that hypomagnesemia and
      hypocalciuria are universal in Gitelman's syndrome; 20% of cases of Bartter's
      syndrome have hypomagnesemia and hypercalciuria. We present a 44-year-old white
      man referred for hypokalemia. Clinical evaluation was unremarkable. He had
      hypokalemia (P(K), 2.8 to 3.0 mEq/L), hypochloremic metabolic alkalosis, mild
      azotemia (serum creatinine, 1.4 to 1.8 mg/dL; creatinine clearance, 59 mL/min),
      normocalcemia, marked persistent hypocalciuria (FE(Ca), 0.08% to 0.09%), and
      normal intact parathyroid hormone levels (51 pg/mL) and glucosuria. He had
      persistent hypermagnesemia (P(Mg), 2.1 to 2.8 mEq/L) with relative hypomagnesuria
      (FE(Mg), 3.2% to 5.2%) given the level of renal impairment and hypermagnesemia.
      Supine plasma renin activity and aldosterone levels were high (11 ng/mL/hr and 43
      ng/dL, respectively). An excessive dietary intake of magnesium, including
      medications, was excluded. Studies were performed after withdrawing all
      medications for 8 days. A maximum water diuresis was established (an oral load of
      20 mL/kg; stable Uosm, 120 mOsm/kg), and free water and solute clearances were
      studied at baseline and after sequential intravenous injections of 125 mg
      chlorothiazide and 40 mg furosemide. The patient had moderate renal impairment
      (technetium diethylene triamine pentacetic acid [DTPA] clearance, 35.4
      mL/min/1.73 m2) and, in contradistinction to Bartter's and Gitelman's syndromes,
      sodium and water handling in the thick ascending limb of the loop of Henle and
      the distal tubule (fractional distal solute reabsorption) was normal, but there
      was evidence of a defect in the proximal tubule reabsorption (glucosuria,
      supranormal C(H2O) and high distal delivery). Hypomagnesuria and hypocalciuria
      appeared to be secondary to an increase in their absorption in the loop of Henle
      (increased excretion following furosemide). In conclusion, this combination of
      metabolic abnormalities has never been described. We postulate a proximal tubular
      defect in the absorption of NaCl leading to hypocalciuria, hypomagnesuria, and
      potassium wasting. Whether the tubular defect is primary or secondary to a renal
      parenchymal disease is, however, unclear.

PMID- 9002539
TI  - Idiopathic membranous nephropathy in identical twins.
AB  - Familial idiopathic membranous nephropathy is rarely reported, despite the
      striking immunogenetic association of the disease with certain HLA antigens. This
      report describes a pair of identical male twins who contemporaneously developed
      idiopathic membranous nephropathy. HLA typing was carried out in the twins and in
      almost all members of their family. Interestingly, HLA antigens that have been
      reported to be associated with idiopathic membranous nephropathy, especially DR3,
      were found not only in the twins, but in the other family members as well. Due to
      similarities between Heymann nephritis and human membranous nephropathy, we
      performed a search for anti-brush border and antipodocyte antibodies. The
      inability to detect these antibodies suggests that they were probably not
      involved in the pathogenesis of these cases.

PMID- 9002541
TI  - Recurrence of immunoglobulin A nephropathy with immunoglobulin A antineutrophil
      cytoplasmic antibodies following renal transplantation.
AB  - We previously reported the presence of immunoglobulin A (IgA) antineutrophil
      cytoplasmic antibodies (ANCAs) in patients presenting IgA nephropathy (IgAN),
      particularly when associated with Henoch-Schonlein purpura. Most of the patients
      exhibited IgA ANCAs directed at an unknown 50-kd neutrophil protein but no IgG
      ANCAs. A subgroup of patients presented IgG as well as IgA ANCAs, suggesting an
      overlap syndrome between Henoch-Schonlein purpura and microscopic polyangiitis.
      We aimed at confirming the correlation of IgA ANCA titer with disease activity in
      a patient presenting IgAN relapse following kidney transplantation. The ANCAs
      were searched for by isotype- and antigen-specific enzyme-linked immunosorbent
      assay. Specificity was confirmed by antigen-specific enzyme-linked immunosorbent
      assay and Western blot analysis. At the onset of the disease in 1989, the patient
      presented with ANCAs of IgA and IgG class with specificity for myeloperoxidase
      and no rheumatoid factor. End-stage renal failure developed 1 year afterward. In
      1991, he received a cadaveric renal allograft, and 9 months later developed acute
      nephrotic syndrome with rapidly progressive renal failure and recurrence of IgAN
      on the kidney transplant. An increase in IgA but not IgG ANCAs was found on
      clinical relapse after kidney transplantation. We conclude that rare patients may
      present an overlap syndrome between IgG ANCA-positive systemic vasculitis and
      IgAN, characterized by the presence of IgG and IgA anti-myeloperoxidase
      antibodies.

PMID- 9002542
TI  - Fibrillary glomerulonephritis associated with hepatitis C viral infection.

PMID- 9002543
TI  - A new classification for renal defects in net acid excretion.
AB  - The traditional classification of the group of disorders called renal tubular
      acidosis (RTA) into proximal and distal subclasses is based on which nephron
      segment is thought to have an abnormal function. Nevertheless, such a distinction
      may not be correct and also does not characterize the pathophysiology of the
      renal acidosis in each patient. In this article, we propose an alternative
      classification, one that is based on the component of net acid excretion that is
      abnormal. We also suggest expanding the definition of net acid excretion to
      include a term that describes the renal handling of metabolizable organic anions
      because their loss in the urine represents the loss of "potential bicarbonate."
      Because a low rate of excretion of ammonium (NH4+) is present in patients with
      both distal and isolated proximal RTA, our initial clinical step in patients with
      hyperchloremic metabolic acidosis (HCMA) is to evaluate the rate of excretion of
      NH4+. The basis for a low rate of excretion of NH4+ is shown by examining the
      urine pH. If the urine pH is low, further studies are performed to determine why
      the availability of NH3 is low; if the urine pH is high, further investigations
      are initiated to examine if the defect in H+ secretion involves the proximal or
      the distal nephron. Conversely, if the rate of excretion of NH4+ is high in a
      patient with HCMA, a component of the degree of acidosis could be attributable to
      a high rate of excretion of metabolizable organic anions. Case examples are
      provided to illustrate the approach and its implications for future molecular
      studies.

PMID- 9002544
TI  - Have we ignored the role of oncotic pressure in the pathogenesis of
      glomerulosclerosis?
AB  - Focal and segmental glomerulosclerosis (FSGS) develops in a number of renal
      conditions, especially those associated with severe nephrotic syndrome or a
      reduction in renal mass. Strong evidence suggests that in diseases associated
      with reduced renal mass that FSGS develops as a consequence of elevated
      glomerular hydrostatic pressure (P(GC)) resulting from single nephron
      hyperfiltration. In nephrotic syndrome, the contribution of an elevated P(GC) is
      less certain. We hypothesize that in both conditions there is an elevation in net
      ultrafiltration pressure (P(UF)), which in nephrotic syndrome is secondary to a
      reduction in glomerular plasma oncotic pressure (piGC) and in conditions with
      reduced renal mass is secondary to an elevated P(GC). The elevated P(UF) would
      result in increased convective forces with trafficking and deposition of
      macromolecules in the mesangium, a process that could trigger local cytokine
      release with the stimulation of cell proliferation and matrix synthesis. In
      addition to explaining why FSGS develops in both nephrotic syndrome and with
      reduced renal mass, the hypothesis explains why the lesion in FSGS is segmental
      and preferentially involves the hilar area. This is because P(UF) varies along
      the glomerular capillary, being highest at the proximal (afferent arteriolar)
      end. In contrast, an elevated P(GC) alone does not readily explain the segmental
      nature of FSGS, because P(GC) remains relatively constant within the glomerulus.
      Thus, the hypothesis suggests an important role for the plasma oncotic pressure
      in the pathogenesis of FSGS. Future studies examining the role of P(UF) and piGC
      in FSGS would be of interest.

PMID- 9002547
TI  - Peer review at NIH in the 21st Century.

PMID- 9002546
TI  - Atrial myxoma in a woman with autosomal dominant polycystic kidney disease type
      2.

PMID- 9002545
TI  - The role of angiotensin II in diabetic nephropathy: emphasis on nonhemodynamic
      mechanisms.
AB  - Several systemic or intrarenal networks of cytokines and growth factors can be
      modulated by the diabetic state. We summarize the status of the renin-angiotensin
      system in diabetes mellitus and review the evidence of its involvement in the
      pathogenesis of diabetic nephropathy. Particular emphasis is placed on the
      nonhemodynamic properties of this vasoactive agent as both a renal growth factor
      and a profibrogenic peptide. Antagonizing the effects of angiotensin II with
      converting enzyme inhibitors is an established protective strategy in the
      management of diabetic nephropathy even in the absence of systemic hypertension.
      This and other indirect evidence from experimental animal studies suggest that
      the intrarenal concentration of angiotensin II may be increased as a result of
      increased synthesis and despite enhanced breakdown, that this peptide
      participates in the progression of diabetic nephropathy. However, down-regulation
      of angiotensin type 1 (AT1)-receptors is one of the abnormalities of both tubules
      and glomeruli in diabetic renal disease. A heightened bioactivation of the
      intrarenal angiotensin II system is therefore likely but not certain. Studies in
      cultured proximal tubular and glomerular mesangial cells have disclosed striking
      similarities between the effects of high glucose-containing medium and of
      treatment with angiotensin II on the growth properties and the induction of
      cytokines in these cells. There may also exist additive effects of angiotensin II
      and high glucose on signal-transduction pathways, such as activation of protein
      kinase C, although the contractile response to angiotensin II may be blunted by
      high glucose in mesangial cells. An important downstream mediator of the effects
      of both angiotensin II and high glucose is the activation of transforming growth
      factor-beta that can mediate at least some of the hypertrophic and profibrotic
      effects of either angiotensin II or high glucose in the diabetic kidney.

PMID- 9002548
TI  - Ad4BP/SF-1, a transcription factor essential for the transcription of
      steroidogenic cytochrome P450 genes and for the establishment of the reproductive
      function.
AB  - Ad4BP/SF-1 was identified as the steroidogenic tissue-specific transcription
      factor regulating the expression of the steroidogenic cytochrome P450 genes. In
      addition to the steroidogenic endocrine tissues such as adrenal cortex, testis,
      and ovary, the factor was found to be expressed in the pituitary gonadotroph and
      the ventromedial hypothalamic nucleus. Considering the roles of the hypothalamus
      pituitary-gonadal axis, it is reasonable to assume that Ad4BP/SF-1 is closely
      associated with the reproductive function of adult animals. Another fundamental
      role of Ad4BP/SF-1 in the fetal development was discovered by gene disruption
      studies. Serious structural and functional defects were observed in the Ad4BP/SF
      1-positive tissues of the gene-disrupted mice. Based on the sexually dimorphic
      expression of Ad4BP/SF-1 in the fetal gonads, the factor is also likely to be
      involved in the gonadal sex differentiation. Because of this functional
      significance during the tissue differentiation, the regulatory mechanism of the
      Ad4BP/SF-1 gene, the mammalian Ftz-F1 gene, has been investigated. The gene is
      controlled by an autoregulatory mechanism in which Ad4BP/SF-1 functions as the
      dominant transcription factor.-Morohashi, K.-I., and Omura, T. Ad4BP/SF-1, a
      transcription factor essential for the transcription of steroidogenic cytochrome
      P450 genes and for the establishment of the reproductive function.

PMID- 9002549
TI  - Regulation of STAT-dependent pathways by growth factors and cytokines.
AB  - Polypeptide growth factors and cytokines elicit their effects by activating
      specific cell-surface receptors, thereby initiating signaling cascades that
      culminate in the induction of specific subsets of genes. Initially identified as
      the primary mediators of interferon-dependent signaling, JAKs and STATs are now
      known to be utilized by many different extracellular signaling proteins. In this
      report we describe how JAK-STAT pathways transduce signals initiated by both
      cytokines and growth factors, focusing on how specificity is achieved through
      STAT-receptor interactions and on how receptor-associated kinases function in
      STAT activation. We also summarize current information on interactions between
      signaling pathways, particularly STAT-Ras cross-talk and the relative importance
      of these two pathways in regulating the transcription of target genes.

PMID- 9002550
TI  - Trinucleotide repeat disorders in humans: discussions of mechanisms and medical
      issues.
AB  - Several human disorders are now known to be caused by expansion of unstable
      trinucleotide repeat sequences, including fragile X syndrome (FRAX), myotonic
      dystrophy (DM), spinal and bulbar muscular atrophy (SBMA, also known as Kennedy
      disease), Huntington disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA),
      spinocerebellar ataxia type 1 (SCA1), Machado-Joseph disease (MJD), and
      Friedreich ataxia. As these diseases are studied in more detail, important
      differences have emerged in the nature of the unstable repeats and the mechanism
      by which the repeat expansions cause disease symptoms. There are already animal
      models of some of these disorders, and these are important resources for studying
      pathology and therapeutic strategies. Diagnostic procedures for these disorders
      are only beginning to be standardized, and effective therapy will have to wait
      for further information on disease mechanisms. Much has been learned since
      discovery of the fragile X syndrome gene in 1991, but much remains to be done.

PMID- 9002551
TI  - Osmotic regulation of gene expression.
AB  - Cells react to increased osmolality with numerous changes in gene expression. The
      specific genes affected differ between species, but the known osmoprotective
      effects of the gene products are remarkably similar, particularly with regard to
      cellular accumulation of compatible organic osmolytes. Here we concentrate on the
      molecular basis for osmotic regulation of gene expression, emphasizing certain
      genes expressed in bacteria, yeast, and the mammalian renal medulla because their
      expression is best understood. Thus, we emphasize 1) bacterial and yeast two
      component histidine kinase systems, each consisting of a membrane osmolality
      sensor and a separate cytoplasmic response regulator that, when phosphorylated,
      alters transcription, 2) volume regulatory increases in cellular K+ salts that
      can prompt increased gene transcription in bacteria through direct effects on DNA
      and that in mammalian renal cells increase transcription, seemingly via trans
      activating proteins, 3) a yeast kinase cascade that transmits an osmotic signal
      to the gene regulating the level of glycerol, and 4) in mammalian cells, several
      homologous cascades that are activated by hypertonicity, but whose osmoregulatory
      targets are not yet known.

PMID- 9002552
TI  - MIF rediscovered: cytokine, pituitary hormone, and glucocorticoid-induced
      regulator of the immune response.
AB  - The protein that has been historically called macrophage migration inhibitory
      factor (MIF) was one of the first cytokine activities to be discovered and was
      originally described to be a T lymphocyte product that inhibited the random
      migration of macrophages. Over the years, additional molecules with MIF
      "activity" have been described and the precise role of the original MIF "protein"
      remained enigmatic. Recent studies have led to the discovery of a pituitary
      mediator that appears to act as the counterregulatory hormone for glucocorticoid
      action within the immune system. Isolated as a product of murine anterior
      pituitary cells, this peptide was sequenced and found to be the mouse homolog of
      MIF. MIF has the unique property of being released from macrophages and T cells
      in response to physiological concentrations of glucocorticoids. The secretion of
      MIF is tightly regulated and decreases at high, anti-inflammatory steroid
      concentrations. Once released, MIF "overrides" or counterregulates the
      immunosuppressive effects of steroids on immune cell activation and cytokine
      production. These observations suggest that MIF fills an important gap in our
      understanding of how the host initiates and controls immunity. Because
      glucocorticoids are an integral part of the host's global response to infection
      or tissue invasion, the physiological role of MIF is to act at an inflammatory
      site or lymph node to counterbalance the profound inhibitory effects of steroids
      on the immune response.

PMID- 9002554
TI  - Selective monitoring of peptidase activities with synthetic polypeptide
      substrates and polyion-sensitive membrane electrode detection.
AB  - A novel method to monitor specific peptidase activities in biological samples as
      complex as undiluted plasma/blood is described. The approach is based on the
      design of synthetic polypeptide substrates in which di- or triarginine sequences
      are linked to each other via one or more other amino acids recognized
      specifically by the peptidase to be determined. Detection of chymotrypsin and
      renin activities using synthetic substrates P4 (F-R-R-R-F-V-R-R-F-NH2) and P5 (R
      R-R-L-L-R-R-L-L-R-R-R), respectively, serves to demonstrate the principles of
      this new assay system. A polyion-sensitive membrane electrode, prepared by doping
      polymer films with dinonylnaphthalene-sulfonate (DNNS), is shown to exhibit
      significant nonequilibrium electromotive force (EMF) responses toward these and
      other polycationic substrates at microgram/milliliter levels under physiological
      conditions. The same electrode, however, exhibits much smaller total EMF response
      toward the shorter fragments of the synthetic peptides generated by peptidase
      activity; hence, the addition of peptidase to a solution containing the synthetic
      substrate yields a change in electrode EMF response, the rate of which is
      proportional to the activity of peptidase present. Other synthetic polycationic
      peptides as well as natural polycationic peptides (e.g., protamine) that lack
      specific cleavage sites for chymotrypsin and renin, yet are detected by the DNNS
      based membrane electrode, do not elicit any significant change in EMF response in
      the presence of the peptidases, confirming the feasibility and utility of the
      proposed bioanalytical method.

PMID- 9002553
TI  - Inducible NO synthase II and neuronal NO synthase I are constitutively expressed
      in different structures of guinea pig skeletal muscle: implications for
      contractile function.
AB  - The expression of NOS isoforms was studied in guinea pig skeletal muscle at the
      mRNA and protein level, and the effect of NO on contractile response was
      examined. Ribonuclease protection analyses demonstrated NOS I and NOS II mRNAs in
      diaphragm and gastrocnemius muscle. In Western blots, NOS I and NOS II
      immunoreactivities were found in the particulate but not the soluble fraction of
      skeletal muscle. NOS activity was found almost exclusively in the particulate
      fraction. About 50% of this activity was Ca2+ independent. In
      immunohistochemistry, the anti-NOS I antibody stained distinct membrane regions
      of muscle fibers. The most intense staining was seen in neuromuscular endplates
      identified by labeling with alpha-bungarotoxin. The anti-NOS II antibody labeled
      muscle fibers that contained alkali-labile myosin ATPase (type I fibers). NOS II
      was located to intracellular structures and was also seen in "specific pathogen
      free" animals. Pretreatment of guinea pigs with bacterial lipopolysaccharide
      (LPS) markedly intensified NOS II staining. Significant NOS III immunoreactivity
      was detected only in vascular endothelium. In functional experiments, tetanic
      muscle contractions were induced in diaphragm and gastrocnemius muscle by
      electrical stimulation of the innervating nerves. Pretreatment of guinea pigs
      with LPS or addition of S-nitroso-N-acetyl-D,L-penicillamine to the organ bath
      markedly decreased tetanic contractions. N(G)-nitro-L-arginine, on the other
      hand, increased contractile force and reversed the effect of LPS. Our data
      indicate that NOS II and NOS I are expressed in different structures of skeletal
      muscle and are involved in the regulation of contractile response.

PMID- 9002555
TI  - The distribution of protein kinase C in human leukocytes is altered in
      microgravity.
AB  - Protein kinase C (PKC) is an ubiquitous enzyme that mediates intracellular signal
      transduction in eukaryotes. Jurkat and U937 cells were exposed to microgravity
      during a Space Shuttle flight and stimulated with a radiolabeled phorbol ester
      (3H-PDBu) that specifically activates and labels several PKC isoforms. Both the
      total amount of 3H-PDBu labeling per cell and the relative distribution of
      labeling between subcellular compartments were altered in microgravity compared
      to onboard and ground 1 g control samples. The amount of total phorbol ester
      labeling per cell was increased approximately twofold in microgravity samples
      when compared with onboard 1 g samples for both cell lines. The subcellular
      distribution of PKC in the cytosol and nuclear fractions appeared to be
      correlated with the applied acceleration. In both cell types the relative amount
      of phorbol ester labeling in the nuclear fraction decreased with applied
      acceleration, whereas the labeling in cytosolic fraction increased with g level.
      No significant differences were observed between labeling levels in the membrane
      fraction in both cell types. Interleukin-1beta synthesis by U937 cells was
      markedly decreased in microgravity when compared to the onboard 1 g control,
      suggesting that the observed alterations in PKC distribution may have functional
      consequences. The results may have important implications for the effect of
      gravity on cellular signal transduction.

PMID- 9002556
TI  - Myelin protein Po as a potential autoantigen in autoimmune inner ear disease.
AB  - We have previously shown that a 30,000 Mr protein extracted from guinea pig inner
      ear tissue is recognized by autoantibodies present in the serum of patients
      suffering from autoimmune inner ear disease. This protein was localized in the
      modiolus and in the organ of Corti. We have now identified this protein by a
      combination of microsequencing and matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry of its tryptic peptides. A partial sequence of
      the protein was thereby determined. These data and 2-dimensional gel
      electrophoresis followed by immunoblotting experiments showed that the 30,000 Mr
      inner ear antigen is the major peripheral myelin protein Po. This suggests that
      protein Po may be an important autoantigen in autoimmune inner ear disease.

PMID- 9002557
TI  - Transgenic mice for the establishment of histidinol-resistant embryonic
      fibroblast feeder layers.
AB  - Gene targeting in mouse embryonic stem cells generates mutations by replacing an
      endogenous chromosomal region with a copy disrupted by a selectable genetic
      marker. The most commonly used selectable marker is the bacterial neo(r) gene,
      which confers resistance in mammalian cells to the antibiotic G418. Use of an
      alternative selectable marker, the Salmonella typhimurium gene hisD, should
      provide expanded applications for gene targeting. The hisD gene encodes the
      protein histidinol dehydrogenase, which catalyzes the conversion of histidinol to
      the amino acid histidine. Histidinol is toxic to mammalian cells, while histidine
      is an essential mammalian amino acid. Consequently, growth selection in cultures
      with media containing histidinol in place of histidine occurs by both histidine
      starvation and histidinol poisoning. The hisD selection is being tested for
      potential use in gene targeting experiments with mouse embryonic stem (ES) cells.
      Currently, most successful gene targeting experiments use primary embryonic
      fibroblast feeder layers, which assist in the maintenance of the pluripotential
      state of the embryonic stem cells. To support ES cell stability under histidinol
      selection, mice transgenic for the S. typhimurium hisD gene have been produced
      and used to generate embryonic fibroblast feeder cells. The transgenic embryonic
      fibroblasts survive under a wide range of histidinol-containing growth conditions
      and support growth of ES cell cultures.

PMID- 9002558
TI  - The effects of calcium channel blockade on agouti-induced obesity.
AB  - We have previously observed that obese viable yellow (Avy/a) mice exhibit
      increased intracellular Ca2+ ([Ca2+]i) and fatty acid synthase (FAS) gene
      expression; further, recombinant agouti protein increases in cultured adipocytes
      and these effects are inhibited by Ca2+ channel blockade. Accordingly, we
      determined the effect of Ca2+ channel blockade (nifedipine for 4 wk) on FAS and
      obesity in transgenic mice expressing the agouti gene in a ubiquitous manner. The
      transgenic mice initially were significantly heavier (30.5+/-0.6 vs. 27.3+/-0.3
      g; P<0.001) and exhibited a 0.81 degrees C lower initial core temperature
      (P<0.0005), an approximately twofold increase in fat pad weights (P=0.002), a
      sevenfold increase in adipose FAS activity (P=0.009), and a twofold increase in
      plasma insulin level (P<0.05) compared to control mice. Nifedipine treatment
      resulted in an 18% decrease in fat pad weights (P<0.007) and a 74% decrease in
      adipose FAS activity (P=0.03), normalized circulating insulin levels and insulin
      sensitivity (P<0.05), and transiently elevated core temperature in the transgenic
      mice, but was without effect in the control mice. These data suggest that agouti
      regulates FAS, fat storage, and possibly thermogenesis, at least partially, via a
      [Ca2+]i-dependent mechanism, and that Ca2+ channel blockade may partially
      attenuate agouti-induced obesity.

PMID- 9002559
TI  - Dietary choline supplementation in pregnant rats increases hippocampal
      phospholipase D activity of the offspring.
AB  - Supplementation with choline during pregnancy in rats causes a long-lasting
      improvement of visuospatial memory of the offspring. The biochemical mechanism of
      this effect may be related to the function of choline as a precursor of
      phosphatidylcholine (PC), the substrate of a receptor-stimulated enzyme,
      phospholipase D (PLD). PLD activation initiates the sequential formation of two
      intracellular messengers, phosphatidic acid and 1,2-sn-diacylglycerol. We
      hypothesized that prenatal choline status may cause long-term modulation of PLD
      catalyzed PC hydrolysis in the hippocampus, a brain region implicated in
      visuospatial memory functions. PLD activity was determined in hippocampal slices
      prelabeled with [3H]glycerol or [3H]oleic acid by measuring the PLD-catalyzed
      formation of [3H]phosphatidylpropanol in the presence of 1-propanol. Slices were
      obtained from male pups born to mothers consuming a control diet, a choline
      supplemented diet, or a choline-free diet from days 11 to 17 of pregnancy. The
      radiolabeling of phospholipid classes was unaffected by the treatments. Prenatal
      choline supplementation significantly increased basal PLD activity in
      [3H]glycerol-labeled slices [by 46% of controls on postnatal day (P) 7 and by 36%
      on P21], and [3H]oleate-labeled slices (by 91% on P7), as well as glutamate
      stimulated PLD activity in [3H]oleate-labeled slices (by 60% on P7). Prenatal
      choline deficiency failed to alter PLD activity. The actions of choline
      apparently required intact cells because in vitro assays of PLD activity in
      hippocampal homogenates, using fluorescent NBD-PC as substrate, revealed no
      differences between groups. The results show that prenatal choline
      supplementation up-regulates basal and receptor-stimulated PLD activity in the
      hippocampus during postnatal development.

PMID- 9002560
TI  - Improvement of ED prediction of cardiac mortality among patients with symptoms
      suggestive of acute myocardial infarction.
AB  - A study was undertaken to evaluate the 1-year risk of cardiac death for patients
      with chest pain/suspected acute myocardial infarction in the emergency department
      (ED) and express the prognosis in a statistical model. Clinical variables and
      electrocardiogram were correlated to cardiac death during 1 year. Cox regression
      model was used to estimate the risk of death as a continuous function of a risk
      score and the time interval. From these, the prognosis for each patient can be
      calculated. There were 6,794 visits by 5,303 patients followed for 1 year, during
      which 604 patients died. The absolute risk of cardiac death can be calculated
      from the independent predictors for cardiac death: age; sex; histories of
      diabetes mellitus, hypertension, and congestive heart failure; and symptoms,
      electrocardiographic pattern, and degree of suspicion of acute myocardial
      infarction on admission. This model allows estimation of the prognosis for every
      patient with chest pain/suspected acute myocardial infarction from data easily
      available in the ED.

PMID- 9002561
TI  - A new index for early prediction of hospitalization in patients with acute
      asthma.
AB  - Data from studies using the factor analysis technique have shown that asthma
      appears to be multidimensional and that most of the subjective and objective
      measures utilized in the assessment of asthma patients represent a much smaller
      number of underlying dimensions. Additionally, several investigators have
      emphasized that evaluation of acute asthma is an ongoing process, as the degree
      and time course of the response to therapy vary considerably between patients.
      The aim of this study was to examine the usefulness of the most common clinical
      and objective measures in the evaluation of acute asthma in the emergency
      department (ED) for predicting the outcome of acute episodes in adults. In an
      effort to identify variables that can predict the outcome of patients with acute
      asthma, 184 adults (age 32.4 +/- 11.6 [mean +/- SD]) (analysis sample) who
      presented to an ED were studied. The inclusion criteria were: (1) age between 18
      and 50 years; (2) a peak expiratory flow rate (PEFR) or forced expiratory volume
      in the first second (FEV1) below 50% of predicted; and (3) no history of chronic
      cough or cardiac, hepatic, renal, or other medical disease. All patients were
      treated with salbutamol delivered with metered-dose inhaler (MDI) into a spacer
      device in 4 puffs actuated at 10-minute intervals and 500 mg of intravenous
      hydrocortisone. The multivariate statistical technique of discriminant analysis
      was utilized to develop the index, and after this, a new sample (n = 91), the
      validation sample, was studied to validate the index. In the analysis sample 163
      patients (89%) were discharged (relapse rate within 7 days = 10%) and 21 (11%)
      were hospitalized (mean duration of hospital stay = 5.75 +/- 2.81 days). The
      discriminant analysis identified three independent variables that make the
      greatest contribution in discriminating between the two groups studied: PEFR
      variation over baseline, PEFR as percent of predicted, and accessory muscle use,
      all measured at 30 minutes after the beginning of treatment. A multifactorial
      index using these three variables presented a sensitivity of 0.86, a specificity
      of 0.96, a positive predictive value of 0.75, and a negative predictive value of
      0.98. The validation sample index sensitivity, specificity, and positive and
      negative predictive values were 0.83, 0.97, 0.83, and 0.97, respectively. In
      conclusion, a predictive index has been developed for evaluating patients with
      asthma who present to an ED. This simple and brief three-item index can
      facilitate an early decision (30 minutes of treatment) to hospitalize patients
      with severe asthma.

PMID- 9002562
TI  - Use of the combination of myoglobin and CK-MB mass for the rapid diagnosis of
      acute myocardial infarction.
AB  - Early identification of patients presenting with myocardial infarction (MI) is
      necessary for rapid initiation of treatment. Currently, MI has been diagnosed
      using the combination of the history, electrocardiogram (ECG), and biochemical
      markers of myocardial necrosis. Unfortunately, all lack sufficient sensitivity
      and specificity to confidently identify most patients with MI in a timely enough
      fashion to influence early intervention. Development of newer immunochemical
      assays for CK-MB mass and myoglobin have allowed for earlier, more rapid
      diagnosis; however, each has important limitations. The diagnostic sensitivity of
      CK-MB mass, myoglobin, and the combination of both were analyzed at the time of
      presentation (0 hours) and again 4 hours later in 101 patients admitted from the
      emergency department (ED) with possible MI. Twenty patients were subsequently
      diagnosed as having MI. The sensitivity of the initial ECG was 60%, compared with
      the sensitivities of the initial myoglobin and CK-MB mass of 70% and 30%,
      respectively. By 4 hours the sensitivity of myoglobin had increased to 85% and CK
      MB mass to 90%. The combination of the initial myoglobin and CK-MB mass had a
      sensitivity of 85%. Combining these two markers, using both the initial and 4
      hour samples, raised the sensitivity to 100%, with a specificity of 100% and
      negative predictive value of 100%. When patients with diagnostic ECGs were
      excluded, the sensitivity of the combination at 0 hours was 80% with a
      specificity of 84%, while the use of the 0- and 4-hour markers had a sensitivity
      and specificity of 100% and 100%, respectively. We conclude that the combination
      of CK-MB mass and myoglobin can rapidly diagnose or exclude MI in as short as 4
      hours after ED presentation, and accuracy is not different in patients without
      diagnostic ECGs. Application of this strategy could potentially lead to more
      rapid intervention in patients with MI, while also allowing early identification
      of lower risk patients.

PMID- 9002563
TI  - A new stable pluronic F68 gel carrier for antibiotics in contaminated wound
      treatment.
AB  - Pluronic F68 was selected as the gel carrier for antimicrobial agents because of
      its extensive use as a wound cleanser in humans without discernable side effects.
      When the concentration of this surfactant is increased to 46%, it forms a water
      soluble gel that can serve as a carrier for antimicrobial agents. The stability
      of this gel can be enhanced by immediately cooling (-15 degrees C) the gel for 24
      hours before storage and subsequent application. Immediate cooling of the gel
      causes hydration of the surfactant that is associated with gel strengthening and
      prolonged shelf life stability. In experimental animals, this stable gel carrier
      containing 0.2% nitrofurazone significantly reduces the bacterial concentration
      of Staphylococcus aureus in wounds to a greater degree than silver sulfadiazine.
      This antimicrobial gel has the same antimicrobial activity as polyethylene glycol
      carriers containing 0.2% nitrofurazone, but does not carry the potential risk of
      polyethylene glycol intoxication.

PMID- 9002564
TI  - Comparison of wound infection rates using plain versus buffered lidocaine for
      anesthesia of traumatic wounds.
AB  - Buffered lidocaine has been shown to be less painful than plain lidocaine for
      anesthetizing wounds. However, the effect of a buffering agent on the local host
      defenses has not been evaluated. The infection rates of wounds anesthetized with
      plain lidocaine versus buffered lidocaine were compared in an observational
      cohort study. Consecutive emergency department patients with traumatic wounds
      that required sutures had a closed-question wound registry sheet prospectively
      completed. Follow-up data were obtained at the time of the return visit. Patients
      failing to return were contacted by telephone. Data were analyzed for wound
      infection rates comparing plain lidocaine with buffered lidocaine. Chi-squared or
      Fisher exact tests were used for statistical analysis. Of 2,711 patients
      analyzed, 2,279 had received plain and 432 had received buffered lidocaine. The
      infection rate for patients treated with plain lidocaine was 3.5%, versus that
      for patients treated with buffered lidocaine, 3.9% (P = .63). After adjustment
      for confounding variables, the infection rate did not differ between plain and
      buffered lidocaine. The infection rates of wounds repaired after anesthesia with
      either plain or buffered lidocaine are similar.

PMID- 9002565
TI  - Does a physician visual assessment change triage?
AB  - A prospective comparative trial was conducted to determine the effect of a
      physician's visual assessment of emergency patients on triage categorization and
      ability at triage to predict admission. The setting was a university, county,
      referral center and residency training site. Participants were a consecutive
      sample of emergency department patients presenting between the times of 0700 and
      2300 hours for 5 weeks. All patients were assigned a triage category by an
      emergency nurse (RN) who saw the patient and by an emergency physician (EP) who
      had the option of performing a visual assessment. Triage categorization was
      compared for interobserver agreement (Kappa [kappa] statistic) and by ability to
      predict admission (MacNemar's test). A total of 3,949 patients was entered. The
      patients that physicians visually assessed were triaged by nurses as more ill (P
      < .001). For triage categories visualized by the EP compared with RN
      categorization, interobserver agreement was 59.8%, kappa = .21. For triage
      categories not visualized by EP compared with RN categorization, interobserver
      agreement was 67.9%, kappa = .45 (P < .001). Sensitivity of EPs to predict
      admission is as follows: all RN triage, 41.3; not seen by EP, 54.9; seen by EP,
      69.3. Specificity is as follows: all RN triage, 93.7; not seen by EP, 88.5, seen
      by EP, 83.9. When physician visual assessment was done, agreement between
      physicians and nurses decreased by more than half. Physicians who included visual
      assessment in patient triage were less likely to agree with RN categorization. A
      visual assessment by the physician improved the sensitivity for predicting
      admission with an only small cost in specificity.

PMID- 9002566
TI  - Barrier precautions in trauma resuscitation: real-time analysis utilizing
      videotape review.
AB  - Blood-borne pathogens threaten all individuals involved in emergency health care.
      Despite recommendations by the Centers for Disease Control and the American
      College of Emergency Physicians, documented compliance with universal precautions
      in trauma resuscitation has been poor. The purpose of this study was to determine
      the factors that predispose to noncompliance with barrier precautions at a level
      I trauma center. Videotapes of trauma resuscitations performed during 1 month (n
      = 66) were reviewed. Full compliance with barrier precautions was documented in
      89.1% of health care workers. Of the noncompliant health care workers, 50.7% were
      emergency department personnel and 47.8% were first responders to the trauma
      resuscitation area. Barrier precaution compliance improved from 62.5% to 91.8%
      with prenotification of patient arrival. Immediate access to barrier equipment is
      essential for all potential in-hospital first responders. Prehospital
      communication systems should be optimized to ensure prenotification.

PMID- 9002567
TI  - Public perception of safety and metal detectors in an urban emergency department.
AB  - Violence within the emergency department (ED) is an area of concern for both the
      staff and public. Emergency physicians and nurses express a great deal of concern
      for their personal safety. The use of weapons in events occurring in the ED has
      prompted a call for the widespread use of metal detectors. The use of these
      devices can meet with resistance regarding concerns over the creation of a bad
      image. This study examined the opinion of the public as to personal safety in an
      urban ED and sought public opinion regarding the use of a metal detector.
      Although the majority of the 303 persons surveyed felt safe (75%) in the ED and
      were satisfied with the level of security (68%), two thirds reported they would
      feel better if a metal detector was in use. Women were more likely than men to
      prefer the use of a metal detector. A small percentage (11%) of the public
      reported a fear of being physically harmed in the ED. Concerns about the
      potential for a negative image caused by use of a metal detector do not appear
      warranted in this urban ED.

PMID- 9002568
TI  - Utility of a software assistant in critical care case review.
AB  - A computer program (the Audit Assistant) was developed to help physicians review
      the care of critically ill emergency department (ED) patients. The program is an
      example of a new class of decision aids that serves to remind physicians to
      consider possibilities, not an artificial intelligence program that actually
      attempts to simulate clinical reasoning. The goal of such programs is to enable
      physicians to reduce errors--in this case to enable reviewers to notice more of
      the errors in care in the cases they are reviewing. The objective of this study
      was to demonstrate on a small set of complex cases that the tested computer
      program enables the physician to perform a better quality review. The issue of
      what constitutes improved case review is addressed. In the first part of the
      study, reviewers reviewed two mock charts without using the Audit Assistant and
      then immediately reviewed the charts again with the assistance of the program.
      The reviews were compared. In the second part of the study, a second reviewer
      also compared the utility of the review of the first reviewer alone and the Audit
      Assistant output as an aid to review, using an additional mock chart. Six
      emergency physicians participated; each was a quality assurance director for the
      ED of one Cleveland area hospital. For the physicians reviewing without the Audit
      Assistant, 41% of critical actions were listed by three or four reviewers. For
      those using the Audit Assistant, 83% of critical actions were listed by three or
      four reviewers. All reviewers preferred the Audit Assistant-suggested list to the
      critical action list generated by a previous reviewer not using the Audit
      Assistant (P < .02). Use of the Audit Assistant improved the completeness and the
      consistency of physician review of mock charts of critically ill ED patients in a
      small series of cases. The critical actions added for review were important, as
      demonstrated by the preferential addition of critical actions chosen by other
      reviewers who were not using the computer program.

PMID- 9002569
TI  - Incarceration of the uterus in pregnancy.
AB  - Uterine incarceration is a rare complication of pregnancy, usually presenting
      between 12 and 20 weeks' gestation, when the gravid uterus normally ascends
      through the pelvic brim. Conditions such as pelvic inflammatory disease,
      endometriosis, postoperative adhesions, posterior wall leiomyomas, and pelvic
      contraction may lead to fixed retroflexion of the uterus, predisposing to this
      condition. A case of incarceration is presented. Clinical features, diagnosis,
      treatment, and potential complications are discussed.

PMID- 9002570
TI  - Obstructive ileus caused by a swallowed foreign body (a "press-through" package)
      and preexisting adhesions.
AB  - A "press-through" package (PTP), because it is large and square-shaped, tends to
      be caught in the esophagus when swallowed. A rare case of obstructive ileus
      induced by a PTP that was swallowed by 54-year-old man with a history of diabetes
      mellitus and acute appendectomy is reported. The PTP was 19 mm x 18 mm and was
      lodged in the cecum, which was stenosed because of preexisting intestinal
      adhesions; consequently, the PTP obstructed the ileus. The PTP was surgically
      removed.

PMID- 9002571
TI  - Removal of nasal foreign bodies in the pediatric population.
AB  - Nasal foreign bodies requiring removal occur commonly in young children.
      Different techniques of removal are needed depending on the type of nasal foreign
      body. A retrospective chart review of a 19-month period identified 60 pediatric
      patients with nasal foreign bodies evaluated in a pediatric emergency department.
      Twenty-four different types of foreign bodies were removed; beads, rocks and
      plastic toys were the most common. Numerous removal techniques were used; forceps
      and Foley catheter techniques were the most common. Most foreign bodies can be
      managed with simple equipment and without requiring otolaryngology consultation.
      Because of the many different nasal foreign bodies found, the physician should be
      skilled in numerous techniques of removal. Each one of these useful techniques is
      reviewed.

PMID- 9002572
TI  - Transnasal butorphanol in the emergency department management of migraine
      headache.
AB  - Transnasal butorphanol (TNB) is a mixed agonist-antagonist opioid that has
      recently been released for the treatment of painful conditions. Patients with a
      history of migraine diagnosed in either of two emergency departments (EDs) with a
      moderate or severe migraine were eligible for this prospective study. Patients
      received 1 mg of TNB at time zero and again in 45 minutes if needed. Twenty-five
      patients were studied. Pain intensity was measured on a 10-cm visual analog
      scale. Mean pain intensity was significantly decreased at 15 minutes and declined
      from 7.9 +/- 1 cm initially to 2.5 +/- 3.3 cm at 90 minutes. Sixty percent of the
      patients required no further treatment. Thirty-six percent experienced side
      effects, with all but 1 being mild or moderate. Seventy-five percent rated the
      treatment as good, very good, or excellent, and 71% would prefer to receive TNB
      for future migraines over other treatment options. TNB offers rapid, effective
      pain relief to the majority of ED migraine patients.

PMID- 9002573
TI  - On-site availability of selected antidotes: results of a survey of Massachusetts
      hospitals.
AB  - Hospital pharmacies in Massachusetts were surveyed to determine their patterns of
      stocking antidotes. Mailed questionnaires were completed by hospital pharmacy
      directors at 82 of 93 acute care institutions (87% response rate). Results
      confirmed great variability in on-site accessibility of antidotes. Only 8 of the
      82 hospitals (9.8%) stocked all of 14 common antidotes inventoried by the survey.
      Even fewer hospital pharmacies stocked specific antidotes (eg, Crotalid anti
      venin, digoxin-specific Fab antibodies, pyridoxine) in an adequate quantity to
      treat one poisoned adult. Larger hospitals and those with a 24-hour pharmacy were
      more likely to have certain antidotes than smaller institutions. We conclude that
      Massachusetts hospitals do not carry complete inventories of 14 common antidotes.
      It is important that poisoned patients be referred to medical centers with
      adequate toxicological care. Improved guidelines for the accessibility of
      antidotes need to be developed and made available to hospital pharmacies and
      emergency departments.

PMID- 9002574
TI  - Traumatic thrombophlebitis of the superficial dorsal vein of the penis: an
      occupational hazard.
AB  - Several cases of thrombophlebitis of the superficial dorsal vein of the penis
      (TSDVP) have been reported in the literature. Etiologies may include any of the
      following: trauma associated with vigorous sexual intercourse; penile
      strangulation caused by a multitude of entities; penile injection; infection;
      neoplasm; or surgery. We report a rare case of traumatic TSDVP in a cab driver
      following repeated injury to the penis by a coin-filled pouch. We review the
      etiologies, mechanism, and treatment of traumatic TSDVP, and attempt to identify
      men who may be at similar occupational risk.

PMID- 9002575
TI  - Multiple impalement with survival.
AB  - An unusual case of multiple impalement by chain-link fence posts is presented in
      which facial, thoracic, and abdominal injuries were sustained following a
      rollover motor vehicle crash. Torso impalement injuries are briefly reviewed and
      guidelines for the management of such injuries are described.

PMID- 9002576
TI  - Spontaneous cervicothoracic epidural hematoma following prolonged valsalva
      secondary to trumpet playing.
AB  - Spontaneous spinal epidural hematoma is an uncommon clinical entity. Patients
      with this disease may present with devastating neurological deficits that can
      mimic other diseases. Emergency physicians should be familiar with this condition
      to assure appropriate therapy in a timely manner. A typical case of spontaneous
      spinal epidural hematoma is presented with review of appropriate differential
      diagnosis and management.

PMID- 9002577
TI  - Delayed presentation of an epidural hematoma.

PMID- 9002579
TI  - Psoas abscess: making an early diagnosis in the ED.
AB  - The variable and nonspecific presentations of psoas abscess, as well as its
      infrequent incidence in the emergency department (ED), can result in delayed
      diagnosis or misdiagnosis. Previous reports have not discussed the diagnostic
      difficulties of psoas abscess from the viewpoint of emergency physicians (EPs),
      especially in light of the widespread use of ED ultrasonography. This report
      describes a 1-year experience between November 1993 and October 1994, during
      which 10 ED patients were diagnosed to have psoas abscess; in 7 cases, diagnoses
      were established in the ED. Patients' mean age was 64.6 years (range, 46 to 76).
      Pain was the most frequently encountered symptom (80%), with 5 patients (50%)
      complaining of flank pain. The triad of fever, flank pain, and limitation of hip
      movement, which is specific for psoas abscess, was present only in 3 patients
      (30%). The mean duration of symptoms was 10.6 days (range, 1 to 30 days). The
      mean time spent to establish the diagnosis was 1.7 days (range, 0 to 7 days). The
      diagnosis of psoas abscess was established by ultrasound in 6 patients, by
      computed tomography (CT) in 3 patients, and by surgery in 1 patient. Four
      patients who presented with either sepsis and nonspecific abdominal/flank pain or
      sepsis and thigh swelling were diagnosed to have psoas abscess by ultrasound
      performed by EPs. Only 3 patients were admitted to the ED with an initial
      diagnosis of psoas abscess. The remaining 7 had the following initial ED
      diagnoses: 2, fever of unknown origin; 2, septic shock; 1, shock; 1, sepsis; and
      1, peritonitis. All but one had manifestations of sepsis. Two patients died of
      septic shock; these two patients had failed to be drained well. This report also
      includes a discussion of the role of EPs and ultrasonography in the diagnosis of
      psoas abscess. With their alertness and their expertise in ultrasonographic
      techniques, EPs can make an immediate diagnosis and arrange an early drainage
      procedure. For patients with sepsis of unknown origin, prolonged fever of unknown
      origin, and some specific manifestations suggestive of psoas abscess, the
      screening ultrasound should scan not only abdominal solid organs but also
      peritoneal cavity and retroperitoneal space. In addition, a flow chart is
      presented for facilitating the diagnosis of psoas abscess in the ED.

PMID- 9002580
TI  - Standard 12-lead ECG versus special chest leads in the diagnosis of right
      ventricular myocardial infarction.
AB  - The case of a 60-year-old woman with an acute inferior transmural myocardial
      infarction associated with a right ventricular myocardial infarction provided an
      opportunity to compare the performance of the 12-lead electrocardiogram (ECG) and
      the right chest leads in the diagnosis of infarction of the right ventricle.
      While the right chest leads revealed unequivocal evidence of ischemic injury
      emanating from the right ventricle, the standard leads II and III showed changes
      compatible with inferior myocardial infarction; familiarity with vectorial
      interpretive concepts of ST segment deviations could provide a hint of an
      associated right ventricular involvement. This report is presented at a time of
      renewed controversy regarding the necessity of special ECG leads in the diagnosis
      of acute right ventricular infarction in the routine emergency department
      environment.

PMID- 9002578
TI  - Real-time ultrasound guided internal jugular vein catheterization in the
      emergency department.
AB  - Establishing central intravenous access in the emergency department (ED) is often
      both crucial and difficult. In patients with nonexistant or ambiguous external
      anatomic landmarks, a real-time ultrasound guided approach to internal jugular
      vein cannulation is useful. In addition, the use of ultrasound guidance in
      internal jugular vein cannulation is supported by reports that have documented
      reductions in number of cannulation attempts, time required to establish central
      access, and rate of complications. The use of ultrasound for establishing central
      venous access has never been described in an ED setting. Two such cases in which
      ultrasound was extremely helpful for establishing central access in an ED are
      reported, the techniques employed for real-time ultrasound guidance of internal
      jugular vein catheterization are described, and the literature that supports the
      use of this technique is reviewed.

PMID- 9002581
TI  - Prehospital cricothyroidotomy by physicians.
AB  - To evaluate cricothyroidotomy in the field and the influence of physicians'
      medical specialty or previous experience on the success rate of this procedure, a
      retrospective study was conducted. Between October 1991 and April 1995, 29
      cricothyroidotomies were performed in the prehospital setting in Israel. Twenty
      six (89.6%) cricothyroidotomies were successfully performed. There was no
      evidence of higher success rate when the performers were surgeons,
      anesthesiologists, or intensive care specialists (100% success), compared to that
      of all other specialties (83.33%). All physicians had successfully completed the
      Advanced Trauma Life Support (ATLS) course, but only three had previously
      performed cricothyroidotomy. Acute complications included failure to establish an
      airway in 3 cases, minor bleeding in 2 cases, and an air leak around the cannula
      in 1 patient. These results show that following brief training (eg, the ATLS
      course) physicians are capable of performing emergency cricothyroidotomy in the
      field with a high success rate and minimal complications, regardless of medical
      specialty.

PMID- 9002582
TI  - An alternate limb lead system for electrocardiograms in emergency patients.

PMID- 9002584
TI  - Pretreatment testing in the emergency department.

PMID- 9002583
TI  - Diagnosis and treatment of sulfonylurea-induced hyperinsulinemic hypoglycemia.

PMID- 9002585
TI  - An unusual cause of small bowel obstruction: strangulated obturator hernia.

PMID- 9002586
TI  - Human body surfing: a new way to incur injury at spectator events.

PMID- 9002588
TI  - A 3-week-old with stridor.

PMID- 9002587
TI  - Etomidate use during emergency intubation of trauma patients.

PMID- 9002589
TI  - A prospective comparison of transnasal butorphanol and acetaminophen with codeine
      for the relief of acute musculoskeletal pain.

PMID- 9002590
TI  - Foreign body airway obstruction: when the Heimlich maneuver fails.

PMID- 9002591
TI  - The worst headache of my life: an unusual presentation of gunshot wound to the
      head.

PMID- 9002592
TI  - Should epinephrine be administered exclusively by the endotracheal route in
      respiratory arrest secondary to asthma?

PMID- 9002593
TI  - Spontaneous pneumothorax following cocaine use in pregnancy.

PMID- 9002594
TI  - Metformin overdose.

PMID- 9002595
TI  - "Flaming Dr. Pepper"--another cause of recreational burn injury.

PMID- 9002596
TI  - Acute appendicitis: the myths of migratory pain and gradual onset of symptoms.

PMID- 9002598
TI  - Sequence composition and organization in the Sh2/A1-homologous region of rice.

PMID- 9002599
TI  - Plant cyclins: a unified nomenclature for plant A-, B- and D-type cyclins based
      on sequence organization.
AB  - The comparative analysis of a large number of plant cyclins of the A/B family has
      recently revealed that plants possess two distinct B-type groups and three
      distinct A-type groups of cyclins. Despite earlier uncertainties, this large
      scale comparative analysis has allowed an unequivocal definition of plant cyclins
      into either A or B classes. We present here the most important results obtained
      in this study, and extend them to the case of plant D-type cyclins, in which
      three groups are identified. For each of the plant cyclin groups, consensus
      sequences have been established and a new, rational, plant-wide naming system is
      proposed in accordance with the guidelines of the Commission on Plant Gene
      Nomenclature. This nomenclature is based on the animal system indicating cyclin
      classes by an upper-case roman letter, and distinct groups within these classes
      by an arabic numeral suffix. The naming of plant cyclin classes is chosen to
      indicate homology to their closest animal class. The revised nomenclature of all
      described plant cyclins is presented, with their classification into groups
      CycA1, CycA2, CycA3, CycB1, CycB2, CycD1, CycD2 and CycD3.

PMID- 9002600
TI  - Functional dissection of a napin gene promoter: identification of promoter
      elements required for embryo and endosperm-specific transcription.
AB  - The promoter region (-309 to +44) of the Brassica napus storage protein gene napA
      was studied in transgenic tobacco by successive 5' as well as internal deletions
      fused to the reporter gene GUS (beta-glucuronidase). The expression in the two
      main tissues of the seed, the endosperm and the embryo, was shown to be
      differentially regulated. This tissue-specific regulation within the seed was
      found to affect the developmental expression during seed development. The region
      between -309 to -152, which has a large effect on quantitative expression, was
      shown to harbour four elements regulating embryo and one regulating endosperm
      expression. This region also displayed enhancer activity. Deletion of eight bp
      from position -152 to position -144 totally abolished the activity of the napA
      promoter. This deletion disrupted a cis element with similarity to an ABA
      responsive element (ABRE) overlapping with an E-box, demonstrating its crucial
      importance for quantitative expression. An internal deletion of the region -133
      to -120, resulted in increased activity in both leaves and endosperm and a
      decreased activity in the embryo. Within this region, a cis element similar to
      the (CA)n element, found in other storage protein promoters, was identified. This
      suggest that the (CA)n element is important for conferring seed specificity by
      serving both as an activator and a repressor element.

PMID- 9002601
TI  - Analysis of kafirin promoter activity in transgenic tobacco seeds.
AB  - Sequences corresponding to 855 bp of 5' promoter region and the transit peptide
      from lambdaGK.1,a genomic clone encoding a 22 kDa alpha-kafirin seed protein from
      sorghum, were translationally fused to a cloned beta-glucuronidase (GUS) coding
      sequence from uidA and transferred to tobacco via Agrobacterium tumefaciens
      mediated transformation. No GUS expression was detectable at any stage of growth
      in stems or leaves of these plants. However, GUS expression was detected in both
      embryo and endosperm tissues of resulting tobacco seeds 10-15 days after
      flowering. Dissected tissues indicate endosperm expression was localized within
      the bulk endosperm and not within the parenchyma cell layer underlying the
      integument. These studies also demonstrate that within dissected tobacco embryos,
      expression from the kafirin promoter was restricted to the mesocotyl region.

PMID- 9002602
TI  - PO149, a new member of pollen pectate lyase-like gene family from alfalfa.
AB  - PO149 is a low-copy-number gene expressed in the late stages of pollen
      development. The promoter region contains no similarities in DNA sequence to
      those of other pollen-specific genes, except for a tobacco sequence (AAATGA),
      which occurs four times in this alfalfa gene and much further upstream than in
      tobacco. Four distinct TATA boxes were detected in the promoter with the distal
      and proximal TATA boxes being separated by a spacer of 269 nucleotides. Hairpin
      loop structures were found in the 5'- and 3'-untranslated regions of PO149 mRNA.
      The coding region of PO149 is interrupted by two introns and encodes a putative
      prepeptide of 450 amino acids with homology to pollen pectate lyase-like proteins
      and pollen allergens. The coding region also contains sequences characteristic of
      both a signal peptide and a nuclear localization signal.

PMID- 9002603
TI  - Localization of plasma membrane H+-ATPase in nodules of Phaseolus vulgaris L.
AB  - Legume nodules have specialized transport functions for the exchange of carbon
      and nitrogen compounds between bacteroids and root cells. Plasma membrane-type
      (vanadate-sensitive) H+-ATPase energizes secondary active transporters in plant
      cells and it could drive exchanges across peribacteroidal and plasmatic
      membranes. A nodule cDNA corresponding to a major isoform of Phaseolus vulgaris
      H+-ATPase (designated BHA1) has been cloned. BHA1 is a functional proton pump
      because after removal of its inhibitory domain and can complement a yeast mutant
      unable to synthesize a H+-ATPase. BHA1 is not nodule-specific, since it is also
      expressed in roots of uninfected plants. It belongs to the subfamily of plasma
      membrane H+-ATPases defined by the Arabidopsis AHA1, AHA2 and AHA3 genes and the
      tobacco PMA4 and corn MHA2 genes. In situ hybridization in nodule sections
      indicates high expression of BHA1 limited to uninfected cells. These results were
      confirmed by immunocytochemistry. The relatively low expression of plasma
      membrane-type H+-ATPase in Rhizobium-infected cells put a note of caution on the
      origin of the vanadate-sensitive ATPase described in preparations of
      peribacteroidal membranes. Also, our results indicate that active transport in
      symbiotic nodules is most intense at the plasma membrane of uninfected cells and
      support a specialized role of uninfected tissue for nitrogen transport.

PMID- 9002604
TI  - Promoter elements controlling developmental and environmental regulation of a
      tobacco ribosomal protein gene L34.
AB  - The rpL34 gene, which encodes a cytoplasmic ribosomal protein with a high
      homology to the rat 60S r-protein L34, was isolated from a genomic library of
      tobacco (Nicotiana tabacum L. cv. Xanthi-nc). A 1500 bp upstream promoter
      fragment was fused to the chloramphenicol acetyltransferase (CAT) reporter gene
      or beta-glucuronidase (GUS) reporter gene and transferred into tobacco plants by
      the Agrobhacterium-mediated leaf disk transformation method. Analysis of CAT
      activity in leaf tissues showed that mechanical wounding increased the rpL34
      promoter activity about 5 times as compared to untreated controls and that the
      promoter activity was further enhanced by plant growth regulators, 2,4
      dichlorophenoxyacetic acid and benzyladenine. Histochemical GUS staining patterns
      of the transgenic plants showed that the rpL34 promoter activity is high in
      actively growing tissues, including various meristems, floral organs, and
      developing fruits. A series of 5' deletion analyses of the rpL34 promoter
      indicated that a 50 bp region located between -179 and -129 is essential for
      wound, auxin and cytokinin responses. Deletion of this region reduced the
      promoter activity to an undetectable level. Insertion of the 50 nucleotide
      sequence into a minimal promoter restored the promoter activity and the promoter
      strength was proportional to the copy number of the upstream sequence. The role
      of TATA and CAAT box regions was studied by a series of 3' deletion analyses. A
      3' deletion up to -28 did not significantly affect the promoter strength. However
      deletion of the promoter up to 70 bp, which deleted the TATA box region,
      significantly reduced promoter activity. Further deletion of the promoter up to -
      104. eliminating the CAAT box region, abolished the promoter activity. These
      results suggest that the TATA box and CAAT box regions are also important for the
      rpL34 promoter activity in addition to the 50 bp upstream region.

PMID- 9002605
TI  - The petunia homologue of tomato gast1: transcript accumulation coincides with
      gibberellin-induced corolla cell elongation.
AB  - Gibberellins (GAs) regulate petunia corolla pigmentation and elongation. To study
      this hormone's effect at the molecular level, we used the tomato gast1 gene as a
      probe to isolate a gibberellin-induced gene (gip) from petunia corollas. The
      deduced sequence of gip exhibited 82% identity with GAST1 protein and contained a
      short, highly hydrophobic N-terminal region. High levels of gip expression were
      detected in elongating corollas and young stem intemodes. When detached corollas
      were grown in vitro in sucrose medium, gip expression was strongly induced by
      gibberellic acid (GA3). GA3-induced gip expression in corollas was inhibited by
      abscisic acid (ABA). The expression of the gene was also induced by GA3 in
      detached young stem segments. Sucrose was not essential for GA-induced gip
      expression in corollas but enhanced its effect. In stems, on the other hand,
      sucrose inhibited the effect of the hormone. The results of the present work
      support the possible role of gip in GA-induced corolla and stem elongation.

PMID- 9002606
TI  - Sequence homology requirements for transcriptional silencing of 35S transgenes
      and post-transcriptional silencing of nitrite reductase (trans)genes by the
      tobacco 271 locus.
AB  - The transgene locus of the tobacco plant 271 (271 locus) is located on a telomere
      and consists of multiple copies of a plasmid carrying an NptII marker gene driven
      by the cauliflower mosaic virus (CaMV) 19S promoter and the leaf-specific nitrite
      reductase Nii1 cDNA cloned in the antisense orientation under the control of the
      CaMV 35S promoter. Previous analysis of gene expression in leaves has shown that
      this locus triggers both post-transcriptional silencing of the host leaf-specific
      Nii genes and transcriptional silencing of transgenes driven by the 19S or 35S
      promoter irrespective of their coding sequence and of their location in the
      genome. In this paper we show that silencing of transgenes carrying Nii1
      sequences occurs irrespective of the promoter driving their expression and of
      their location within the genome. This phenomenon occurs in roots as well as in
      leaves although root Nii genes share only 84% identity with leaf-specific Nii1
      sequences carried by the 271 locus. Conversely, transgenes carrying the bean Nii
      gene (which shares 76% identity with the tobacco Nii1 gene) escape silencing by
      the 271 locus. We also show that transgenes driven by the figwort mosaic virus
      34S promoter (which shares 63% identity with the 35S promoter) also escape
      silencing by the 271 locus. Taken together, these results indicate that a high
      degree of sequence similarity is required between the sequences of the silencing
      locus and of the target (trans)genes for both transcriptional and post
      transcriptional silencing.

PMID- 9002607
TI  - Comparative gene expression in sexual and apomictic ovaries of Pennisetum ciliare
      (L.) Link.
AB  - Limited emphasis has been given to the molecular study of apomixis, an asexual
      method of reproduction where seeds are produced without fertilization. Most
      buffelgrass (Pennisetum ciliare (L.) Link syn = Cenchrus ciliaris L.) genotypes
      reproduce by obligate apomixis (apospory); however, rare sexual plants have been
      recovered. A modified differential display procedure was used to compare gene
      expression in unpollinated ovaries containing ovules with either sexual or
      apomictic female gametophytes. The modification incorporated end-labeled poly(A)+
      anchored primers as the only isotopic source, and was a reliable and consistent
      approach for detecting differentially displayed transcripts. Using 20 different
      decamers and two anchor primers, 2268 cDNA fragments between 200 and 600 bp were
      displayed. From these, eight reproducible differentially displayed cDNAs were
      identified and cloned. Based on northern analysis, one cDNA was detected in only
      the sexual ovaries, two cDNAs in only apomictic ovaries and one cDNA was present
      in both types of ovaries. Three fragments could not be detected and one fragment
      was detected in ovaries, stems, and leaves. Comparison of gene expression during
      sexual and apomictic development in buffelgrass represents a new model system and
      a strategy for investigating female reproductive development in the angiosperms.

PMID- 9002608
TI  - G2-and early-M-specific expression of the NTCYC1 cyclin gene in Nicotiana tabacum
      cells.
AB  - We have previously reported the isolation of a cDNA encoding a mitotic cyclin,
      NTCYC1, from a tobacco cell suspension library. Here we describe the expression
      patterns of NTCYC1 and of Ntsuc1, a suc 1 plant homologue, in synchronized
      tobacco cell suspensions. Furthermore, the expression pattern of this cyclin is
      compared to that of Ntcdc2-1, a Nicotiana tabacum homologue of cdc2. While no
      NTCYC1 transcript was detected in cells synchronized in the G1 and S phases,
      NTCYC1 expression was observed in late G2 and early M phases, disappearing in the
      G1' of a new cell cycle. On the other hand, Ntsuc1 and Ntcdc2-1 exhibited a
      constitutive expression during the cell cycle. A functional analysis performed by
      microinjecting NTCYC1 mRNA into immature Xenopus oocytes, indicates that NTCYC1
      could participate in the control of the G2/M transition in plant cells.
      Subsequently NTCYC1 expression was used to assess the status of mesophyll cells
      in expanded leaves of N. tabacum. Depending on leaf position along the shoot
      axis, a large population of mesophyll cells appeared with a 4C DNA content,
      suggesting a G2 arrest. It was found that leaves with such a population also
      contained high levels of NTCYC1 transcripts. With respect to these results
      concerning a naturally occurring G2-arrested cell population, the regulation of
      NTCYC1 expression in planta is discussed.

PMID- 9002609
TI  - Regulation, unique gene organization, and unusual primary structure of carbon
      fixation genes from a marine phycoerythrin-containing cyanobacterium.
AB  - Marine phycoerythrin-containing cyanobacteria are major contributors to the
      overall productivity of the oceans. The present study indicates that the
      structural genes of the carbon assimilatory system are unusually arranged and
      possess a unique primary structure compared to previously studied cyanobacteria.
      Southern blot analyses of Synechococcus sp. strain WH7803 chromosomal DNA
      digests, using the ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco)
      large subunit gene from Synechococcus sp. strain PCC6301 as a heterologous probe,
      revealed the presence of a 6.4 kb HindIII fragment that was detectable at only
      low stringency. Three complete open reading frames (ORFs) were detected within
      this fragment. Two of these ORFs potentially encode the Synechococcus sp. strain
      WH7803 rbcL and rbcS genes. The third ORF, situated immediately upstream from
      rbcL, potentially encodes a homologue of the ccmK gene from Synechococcus sp.
      strain PCC7942. The deduced amino acid sequences of each of these ORFs are more
      similar to homologues among the beta/gamma purple bacteria than to existing
      cyanobacterial homologues and phylogenetic analysis of the Rubisco large and
      small subunit sequences confirmed an unexpected relationship to sequences from
      among the beta/gamma purple bacteria. This is the first instance in which the
      possibility has been considered that an operon encoding three genes involved in
      carbon fixation may have been laterally transferred from a purple bacterium.
      Analysis of mRNA extracted from cells grown under diel conditions indicated that
      rbcL, rbcS and ccmK were regulated at the transcriptional level; specifically
      Rubisco transcripts were highest during the midday period, decreased at later
      times during the light period and eventually reached a level where they were all
      but undetectable during the dark period. Primer extension analysis indicated that
      the ccmK, rbcL and rbcS genes were co-transcribed.

PMID- 9002610
TI  - Cloning and analysis of the gene for cystathionine gamma-synthase from
      Arabidopsis thaliana.
AB  - A cDNA clone, CGS1, encoding cystathionine gamma-synthase (CGS) from Arabidopsis
      thaliana was selected by complementation of CGS mutant strain of Escherichia coli
      (metB). Cells expressing CGS1 can grow on medium lacking Met and contain CGS
      enzyme activity. Genomic DNA blot analysis of A. thaliana revealed that there is
      a single gene homologous with CGS1. A genomic fragment carrying CGS1 was cloned
      and sequenced. Through combined analysis of the cDNA and genomic clone it was
      determined that the CGS1 coding sequence is 1692 bp, encodes a 563 amino acid, 60
      kDa protein, and is interrupted by ten introns. A transcriptional initiation site
      was detected 260 bp 5' of the initiator codon. The predicted amino acid sequence
      of CGS1 contains a consensus pyridoxal phosphate-binding site and is similar to
      MetB of E. coli, with which it is 35 percent identical. The CGS1 product has a
      sequence at the amino terminus that resembles a transit peptide for localization
      to plastids. At least 160 amino acids from the amino terminus of the CGS1 enzyme
      are not essential for enzymatic activity.

PMID- 9002611
TI  - Apoptosis in barley aleurone during germination and its inhibition by abscisic
      acid.
AB  - During germination of barley grains, DNA fragmentation was observed in the
      aleurone. The appearance of DNA fragmentation in the aleurone layer, observed by
      TUNEL staining in aleurone sections, started near the embryo and extended to the
      aleurone cells far from the embryo in a time dependent manner. The same spatial
      temporal activities of hydrolytic enzymes such as alpha-amylase were observed in
      aleurone. DNA fragmentation could also be seen in vitro under osmotic stress, in
      isolated aleurone. During aleurone protoplast isolation, a very enhanced and
      strong DNA fragmentation occurred which was not seen in protoplast preparations
      of tobacco leaves. ABA was found to inhibit DNA fragmentation occurring in barley
      aleurone under osmotic stress condition and during protoplast isolation, while
      the plant growth regulator gibberellic acid counteracted the effect of ABA.
      Addition of auxin or cytokinin had no significant effect on DNA fragmentation in
      these cells. To study the role of phosphorylation in ABA signal transduction
      leading to control of DNA fragmentation (apoptosis), the effects of the
      phosphatase inhibitor okadaic acid and of phenylarisine oxide on apoptosis were
      studied. We hypothesize that the regulation of DNA fragmentation in aleurone
      plays a very important role in spatial and temporal control of aleurone
      activities during germination. The possible signal transduction pathway of ABA
      leading to the regulation of DNA fragmentation is discussed.

PMID- 9002612
TI  - T-DNA integration into genomic DNA of rice following Agrobacterium inoculation of
      isolated shoot apices.
AB  - This paper establishes that the isolated shoot meristem of monocotyledons can be
      infected and transformed using Agrobacterium. Since this explant from nearly any
      cereal cultivar can rapidly regenerate into a plant, using this explant
      effectively eliminates the genotype regeneration restrictions to cereal crop
      transformation allowing direct transformation of elite germplasm. Shoot apices of
      Oryza sativa L. Tropical Japonica, cv. Maybelle were explants used for
      cocultivation, and gene transfer was accomplished using Agrobacterium containing
      plasmids for the bar gene expression driven by the CaMV 35S promoter or by the
      rice actin 1 promoter. Experiments to determine the survival rates of isolated
      shoot apices on media containing the herbicide, glufosinate-ammonium (PPT),
      established that no shoot apices survived on 0.5 or 1.0 mg/l PPT. After shoot
      apices were cocultivated with Agrobacterium, 2.8% (overall 20 out of 721 shoot
      apices) survived on 0.5 mg/l PPT. Results demonstrated that the use of the actin
      1 promoter-based expression vector and an extra-wounding treatment of the
      meristematic cells appeared to be most effective in promoting transformation.
      Integration, expression and transmission of the transferred foreign genes in
      primary, R1 and R2 generation plants were confirmed by molecular analyses and
      herbicide application tests. A germination test of R2 progeny from one of the
      transgenic plants (R1) established a phenotype segregation ratio showing a non
      Mendelian inheritance pattern. Inactivation of the transferred foreign gene in R2
      progeny appeared to result from transgene methylation.

PMID- 9002614
TI  - Flavonols are not essential for fertilization in Arabidopsis thaliana.
AB  - Flavonols are plant metabolites suggested to serve a vital role in fertilization
      of higher plants. Petunia and maize plants mutated in their flavonol biosynthesis
      are not able to set seed after self-pollination. We have investigated the role of
      these compounds in Arabidopsis thaliana. Like in all other plant species, high
      levels of flavonols could be detected in pollen of wild-type A. thaliana. No
      flavonols were detected in reproductive organs of the A. thaliana tt4 mutant in
      which the chs gene is mutated. Surprisingly, this mutant did set seed after self
      fertilization and no pollen tube growth aberrations were observed in vivo. The
      role of flavonols during fertilization of Arabidopsis is discussed.

PMID- 9002613
TI  - Cloning and expression of a plant homologue of the small subunit of the Golgi
      associated clathrin assembly protein AP19 from Camptotheca acuminata.
AB  - Clathrin-coated vesicles (CCVs) are involved in selective protein transport in
      eukaryotes. AP-1 and AP-2 are protein complexes found in the CCVs of the Golgi
      apparatus and the plasma membrane respectively. AP19 is the smallest polypeptide
      chain components of AP-1. We have identified a cDNA clone (CAP19) encoding a
      putative homologue for the assembly protein AP19 from the Chinese medicinal tree,
      Camptotheca acuminata. The deduced polypeptide contains 161 amino acids and has a
      predicted Mr of 18820. DNA blot analysis suggests that the AP19S of C. acuminata
      are encoded by a small gene family. CAP19 was expressed ubiquitously throughout
      the plant suggesting that it may be involved in general Golgi-mediated secretion.

PMID- 9002615
TI  - Characterization of the molecular defect in a null allele of the opaque-2 locus
      of maize.
AB  - The molecular defect in an opaque-2 (o2) mutant, previously characterized as a
      null allele, has been identified as containing an insertion of the transposable
      element of the Bergamo (Bg) family. Restriction mapping and partial sequence
      analysis of the Bg in the o2 null allele indicates that this element is distinct
      from the previously described Bg as well as the defective Bg (rbg) of the o2m(r)
      allele. It is, however, inserted at the same site in O2 as the rbg of o2m(r) and
      can transpose when Bg is present. This study shows that, depending on genetic
      background, this allele may not behave as a stable null which could dramatically
      influence the conclusions drawn from experiments based on this particular mutant.

PMID- 9002616
TI  - cDNA cloning and characterization of a 3'/5'-O-methyltransferase for partially
      methylated flavonols from Chrysosplenium americanum.
AB  - Enzymatic O-methylation of plant secondary metabolites is an important mechanism
      for the inactivation of reactive hydroxyl groups and for the modification of
      their solubility. A cDNA clone (pFOMT3') encoding the gene for the 3'/5'-O
      methylation of partially methylated flavonols was isolated from Chrysosplenium
      americanum (Saxifragaceae). We used a PCR fragment obtained with degenerate
      oligonucleotides designed from conserved regions of various O-methyltransferases
      (OMTs). The pFOMT3' cDNA sequence shows about 67-85% similarity to other plant
      OMT sequences. The recombinant protein expresses strict specificity for positions
      3'/5' (meta) of partially methylated flavonols, but does not accept quercetin or
      caffeic acid for further methylation. Southern blot analysis of the genomic DNA
      probed with an OMT sequence suggests the presence of a number of related genes in
      this species, consistent with the multiple enzymatic methylations involved in the
      biosynthesis of polymethylated flavonols in this plant.

PMID- 9002617
TI  - Bacterial expression of an active class Ib chitinase from Castanea sativa
      cotyledons.
AB  - Ch3, an endochitinase of 32 kDa present in Castanea sativa cotyledons, showed in
      vitro antifungal properties when assayed against Trichoderma viride. The
      characterization of a cDNA clone corresponding to this protein indicated that Ch3
      is a class Ib endochitinase that is synthesized as a preprotein with a signal
      sequence preceding the mature polypeptide. Bacterial expression of mature Ch3
      fused to the leader peptide of the periplasmic protein ompT resulted in active
      Ch3 enzyme. A plate assay was adapted for semi-quantitative determination of
      chitinase activity secreted from cultured bacteria, which should facilitate the
      identification of mutants with altered capacity to hydrolyse chitin.

PMID- 9002619
TI  - Developmental expression and regulation by light of two closely related beta
      tubulin genes in Lupinus albus.
AB  - We present here the characterization of a Lupinus albus beta-tubulin gene, TubB2,
      which is closely related to TubB1. Both TubB1 and TubB2 transcripts are present
      in the embryonic axis of lupin dry seeds. The patterns of developmental
      expression of TubB1 and TubB2 beta-tubulin genes are strongly correlated. Both
      genes are expressed at higher levels in hypocotyls of 7-day-old etiolated plants
      compared to hypocotyls from plants grown under light/dark cycles. When etiolated
      plants are exposed to continuous white light, differential changes in the steady
      state levels of the TubB1 and TubB2 mRNAs from hypocotyls are observed. These
      changes are accompanied by an inhibition of hypocotyl extension.

PMID- 9002618
TI  - Nitrogen metabolism in actinorhizal nodules of Alnus glutinosa: expression of
      glutamine synthetase and acetylornithine transaminase.
AB  - Two nodule cDNA clones representing genes involved in Alnus glutinosa nitrogen
      metabolism were analysed. ag11 encoded glutamine synthetase (GS), the enzyme
      responsible for ammonium assimilation, while ag118 encoded acetylornithine
      transaminase (AOTA), an enzyme involved in the biosynthesis of citrulline, the
      nitrogen transport form in Alnus. GS mRNA was found at highest levels in root
      nodules, where it was present in the infected cells as well as in the cells of
      the pericycle of the vascular system. AOTA transcripts were found at high levels
      in nodules, confined to the infected cells, suggesting that in nodules of A.
      glutinosa, citrulline biosynthesis takes place mainly in the infected cells.

PMID- 9002620
TI  - Site-directed mutagenesis of the CP 47 protein of photosystem II: alteration of
      conserved charged residues which lie within lethal deletions of the large
      extrinsic loop E.
AB  - The intrinsic chlorophyll-protein CP 47 is a component of photosystem II which
      functions in both light-harvesting and oxygen evolution. The large extrinsic loop
      E of this protein has been shown to interact with the oxygen-evolving site.
      Previously, Vermaas and coworkers have produced a number of deletions within loop
      E which yielded mutants which were unable to grow photoautotrophically and which
      could not evolve oxygen at normal rates. During the course of our site-directed
      mutagenesis program in Synechocystis 6803, we have altered all of the conserved
      charged residues which were present within six of these deletions. All ten of
      these mutants were photoautotrophic and evolved oxygen at normal rates. We
      speculate that the severe phenotypes of the deletion mutants observed by Vermaas
      and coworkers is due to large structural perturbations in the extrinsic loop E of
      CP 47.

PMID- 9002621
TI  - Details of T-DNA structural organization from a transgenic Petunia population
      exhibiting co-suppression.
AB  - Analysis of Agrobacterium-transferred DNA (T-DNA) revealed strong correlations
      between transgene structures and floral pigmentation patterns from chalcone
      synthase (chs) co-suppression among 47 Petunia transformants. Presented here are
      the full details of T-DNA structural organization in that population. Sixteen
      transformants (34%) carried one T-DNA copy while 31 (66%) carried 106 complete
      and partial T-DNA elements in 54 linkage groups. Thirty linkage groups contained
      multiple T-DNA copies; 15 of these contained only contiguously repeated copies, 8
      contained only dispersed copies and 7 contained both. Right-border inverted
      repeats were three times more frequent than left-border inverted or direct
      repeats. Large fragments of binary-vector sequences were linked to the T-DNA in
      seven plants.

PMID- 9002623
TI  - A gene encoding a major Kunitz proteinase inhibitor of storage organs of winged
      bean is also expressed in the phloem of stems.
AB  - Winged bean Kunitz chymotrypsin inhibitor (WCI) accumulates abundantly in seeds
      and tuberous roots, and small amounts of the WCI protein and mRNA can also be
      detected in stems. In this study, we analyzed the localization of the WCI protein
      in stems of winged bean. The results demonstrated that the WCI protein was
      localized in sieve tubes. Furthermore, we showed that the 5' region of the WCI-3b
      gene, which exhibited strong transcriptional activity in developing seeds, also
      promoted transcription of a reporter gene in the phloem of stems of transgenic
      tobacco.

PMID- 9002622
TI  - Cloning and characterization of PO22, a pollen-expressed gene in alfalfa.
AB  - Genomic and cDNA clones have been isolated for a new gene (PO22) expressed in
      mature pollen of alfalfa. PO22 represents a single- or low-copy gene containing 4
      introns, 2 transcriptional start sites, and coding for a predicted protein of 340
      amino acids with no signal peptide and a coiled coil structure of 39 amino acids
      near the carboxyl end. The amino acid sequence of PO22 is 38% identical to that
      of an early nodule-specific gene (ENOD8), also from alfalfa.

PMID- 9002624
TI  - Nucleotide sequence analysis of a novel globulin1 null allele from the Illinois
      high protein strain of maize.
AB  - The highly polymorphic maize globulin1 (glb1) gene encodes an abundant embryo
      storage protein. The present study extends the analysis of glb1 variants to
      further explore the nature of polymorphism at this locus. The null allele Glb1
      N1Hb, derived from the Illinois High Protein (IHP) strain of maize was
      characterized at the molecular level by nucleotide sequence analysis. Among other
      differences, a single-base insertion leading to a premature termination codon in
      the carboxyl-terminal half of the otherwise normal protein was observed. The
      likely reasons for the absence of GLB1 protein accumulation in the IHP strain of
      maize are discussed.

PMID- 9002625
TI  - Mrs, a new subfamily of Tourist transposable elements.
AB  - We have characterised a new family of repetitive sequences that we have named Mrs
      (maize repetitive sequences). Mrs elements are associated with different maize
      genes and seem to be specific for the genome of Zea species. Mrs elements are
      short, AT-rich and contain terminal inverted repeats (TIRs). The sequence of
      their TIRs, as well as the fact that they are flanked by short repetitions that
      tend to be TAA, allows us to propose Mrs as a new subfamily of Tourist
      transposable elements.

PMID- 9002627
TI  - Uptake and salvage of hypoxanthine mediates developmental arrest in
      preimplantation mouse embryos.
AB  - Preimplantation mouse embryos become arrested after first or second cleavage when
      cultured in hypoxanthine-supplemented Whitten's medium. We present evidence that
      the hypoxanthine-induced arrest is dependent on uptake and salvage of
      hypoxanthine and depletion of phosphoribosylpyrophosphate (PRPP) levels.
      Hypoxanthine uptake increased during the 2-cell stage and was augmented by
      glucose. HPLC analysis of [14C]hypoxanthine metabolism revealed that hypoxanthine
      was salvaged and converted to ATP and guanosine triphosphate (GTP), with a shift
      to more guanyl nucleotide production at the 3- to 4-cell stage. In embryos from
      mice with a null mutation for the salvage enzyme hypoxanthine-guanine
      phosphoribosyltransferase, hypoxanthine did not block development nor was it
      taken up by the embryos. Glucose, which is required for the hypoxanthine-induced
      arrest, produced a 5.3-fold increase in PRPP levels at the 2-cell stage, which
      was eliminated by hypoxanthine. We conclude that metabolism of hypoxanthine to
      nucleotides mediates its inhibitory action on preimplantation mouse embryos via
      negative feedback on PRPP synthetase, ultimately resulting in decreased PRPP
      availability and arrest of other PRPP-dependent pathways. Finally, reversal of
      the block by EDTA and cAMP-elevating agents may be mediated by alterations in
      hypoxanthine or glucose uptake, or by changes in the relative metabolism of
      hypoxanthine.

PMID- 9002626
TI  - Isolation and analysis of the soybean SGA2 gene (cDNA), encoding a new member of
      the plant G-protein family of signal transducers.
AB  - We have isolated a cDNA clone from Glycine max, named SGA2, coding for a G alpha
      subunit protein. The encoded polypeptide, SG alpha2, shows a molecular mass of 45
      kDa and contains most of the conserved regions involved in guanine nucleotide
      binding and hydrolysis. Comparison at the nucleotide and amino acid sequence
      levels with the other plant G alpha's shows a high degree of conservation (>85%
      similarity). Phylogenetic analysis of these plant genes with the other G alpha's
      from different species clearly indicate that those proteins represent a new
      member of the heterotrimeric G-protein family, named Gp. Tissue localization of
      SGA2 transcripts in root, stem and leaf organs shows that this gene is widely
      expressed throughout the plant although it is most abundant in the vascular
      tissues of all these organs. Furthermore, the transcript is more abundant in
      young tissues and organ primordia than mature tissues. The high degree of
      sequence conservation among the plant G alpha's and the differences to other
      species of other kingdoms, suggest that plant G proteins may function in
      specialized signalling processes.

PMID- 9002628
TI  - Expression and distribution of androgen-binding protein/sex hormone-binding
      globulin in the female rodent reproductive system.
AB  - Androgen-binding protein (ABP)/sex hormone-binding globulin gene expression has
      been described in the rat testicular Sertoli cell and brain. The extracellular
      protein is thought to regulate the bioavailability of sex steroids, but may have
      a more complex function as a hormone or growth factor. Transgenic mice were
      developed with a 5.5-kilobase (kb) rat DNA fragment containing the ABP gene with
      all 8 exon sequences and 1.5 kb upstream of the transcription start site.
      Expression of the gene was observed in the testis and brain, but not in other
      examined tissues of the transgenic mice. In this paper we describe ABP gene
      expression in ovaries of transgenic mice that contain the rat gene; a lower level
      of ABP mRNA was also detected in the transgenic uterus. Northern blot analysis
      also detected ABP mRNA in rat ovary. The hybridizing species in the rat and
      transgenic mouse ovaries and uteri were the size of testicular ABP mRNA (1.7 kb).
      Except in the transgenic mouse brain, there was no detectable hybridizing RNA in
      the other transgenic tissues examined. The plasma, ovary, and uterus of the
      transgenic mice all contained elevated ABP (dihydrotestosterone [DHT]-binding)
      activities as compared to those of wild-type littermates; other wild-type and
      transgenic tissues were negative for DHT binding. Immunohistochemistry revealed
      increased immunoreactivity in the transgenic oviduct and uterus, but not the
      ovary. In the oviduct, the intense immunoreactivity was associated with the
      epithelium, whereas in the uterus it was primarily associated with the luminal
      epithelium and glands. Phenotypic abnormalities of the homozygous transgenic mice
      included reduced fecundity resulting in small litters. We conclude that ABP may
      function in the female reproductive system to increase the local concentrations
      of sex steroids or to sequester them in key target organs. Studies in the female
      will aid in elucidating the functions of ABP in male and female reproduction.

PMID- 9002629
TI  - Overexpression of androgen-binding protein/sex hormone-binding globulin in male
      transgenic mice: tissue distribution and phenotypic disorders.
AB  - The rat androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) gene in
      transgenic mice was previously shown to be specifically expressed in the testes.
      This study verifies a Sertoli cell location of ABP and translation of testicular
      ABP mRNA in the transgenic mice by dihydrotestosterone (DHT)-binding assays and
      immunohistochemistry. DHT-binding activities in the testis and epididymis of the
      hemizygous transgenic mice were elevated 20-fold as compared to activity in the
      wild-type tissues. DHT-binding activities were also elevated in blood plasma at
      least 25- to 50-fold in the transgenic mice; binding was undetectable in the
      plasma from control mice. Immunohistochemical analysis revealed that the
      transgenic testicular ABP was primarily in the cytoplasm of Sertoli cells and
      lumen of the seminiferous tubules. In some tubules, intense staining also was
      associated with spermatids. After transport to the epididymis, there were large
      amounts of immunoreactive ABP internalized in the epithelium of the initial
      segment and proximal caput. The increased levels of plasma and testicular ABP had
      no effect on levels of testosterone; there was a 30-fold range of plasma and
      testicular testosterone levels in the wild-type and transgenic mice. Increased
      ABP levels in the transgenic mice were associated with structural and functional
      abnormalities in the testis. Abnormal spermatogenesis resulted in extensive
      structural changes in the transgenic testis; the degree of the defect varied from
      near normality to the loss of most germ cells. In the affected mice, seminiferous
      tubules had smaller diameters and decreased numbers of germ cells, particularly
      in the spermatid stages of differentiation. Pyknotic nuclei and multinucleated
      cells were associated with the spermatids in the defective tubules, but not in
      the wild-type tubules. Consequently, mice with the spermatogenic disorder had
      reduced epididymal sperm numbers. The variable spermatogenic disorder was
      associated with variable male fertility. The homozygous transgenic male and
      female mice also had a serious motor dysfunction affecting their hind limbs. This
      study demonstrates how the transgenic mouse model can be used to study ABP's
      function, and the data support several hypotheses on its function in the testis
      and epididymis.

PMID- 9002630
TI  - Antibody responses and infertility in mice following oral immunization with
      attenuated Salmonella typhimurium expressing recombinant murine ZP3.
AB  - Ovarian ZP3, the primary sperm receptor, is a major glycoprotein of mouse zona
      pellucida (ZP). Because antibodies raised against ZP3 block sperm-egg
      interaction, ZP3 has been considered a candidate immunogen in the development of
      a contraceptive vaccine. This study explored the possibility of using an
      attenuated Salmonella typhimurium vaccine strain expressing recombinant ZP3 to
      elicit an antibody response and infertility in mice. A cDNA sequence generated by
      the polymerase chain reaction encoding 342 amino acid residues (23-364) of the
      mouse (m)ZP3 was cloned into an Asd+ vector. An avirulent Salmonella vaccine
      strain stably expressed the ZP3 polypeptide and colonized the internal organs of
      mice after oral inoculation. Oral immunization of female BALB/c mice with the
      recombinant Salmonella vaccine strain expressing mZP3 induced significant levels
      of anti-native ZP IgG antibodies in serum and IgA antibodies in vaginal
      secretions. The IgG antibodies thus induced also bound to ZP in vivo. When mated
      with males, 3 of 6 females immunized with the recombinant Salmonella were
      infertile. In contrast, none of the mice that received Salmonella containing the
      vector plasmid produced antibodies to ZP and all were fertile. No ovarian
      inflammation was observed in the immunized mice at autopsy. The results suggest a
      potential oral contraceptive vaccine to control populations of rodent vectors of
      disease and to induce reversible infertility in humans.

PMID- 9002631
TI  - Atomic force microscope analysis of chromatin volumes in human sperm with head
      shape abnormalities.
AB  - We used the atomic force microscope to perform volume measurements on individual
      human sperm nuclei under ambient conditions. Data obtained for normal sperm and
      for sperm from seven of the nine classes of head-shape abnormality revealed that
      the nuclear volumes were essentially identical for sperm in each headshape class,
      even though the projected areas and shapes of the nuclei have were shown to vary
      widely. These results indicate that the abnormal sperm head morphologies found at
      a rate of 25-40% in fertile males are not caused by factors that affect the
      volume of sperm chromatin, such as the DNA content of the sperm nucleus,
      differences in chromatin organization, or the extent of DNA compaction.

PMID- 9002632
TI  - Monoclonal antibody against phosphatidylserine inhibits in vitro human
      trophoblastic hormone production and invasion.
AB  - Naturally occurring antiphospholipid (aPL) antibodies against cardiolipin (CL)-
      and phosphatidylserine (PS)-dependent antigens are associated with placental
      dysfunction and unsuccessful pregnancy. Murine monoclonal aPL antibodies react
      with placental trophoblast and may interfere with normal trophoblastic function.
      In this study, we evaluated the expression of phospholipid-dependent antigens
      during trophoblast differentiation and measured the effects of monoclonal aPL
      antibodies on two in vitro aspects of trophoblast differentiation: hormone
      production and invasion into filters coated with extracellular matrix. Murine
      monoclonal IgM aPL antibodies that differentiated between PS and CL were used:
      3SB9b reacted only with PS (CL-/PS+), D11A4 reacted only with CL (CL+/PS-), and
      BA3B5C4 reacted with both CL and PS (CL+/PS+). Isolated trophoblasts were
      cultured for 4 days, and reactivity with monoclonal aPL antibodies was evaluated
      daily. BA3B5C4 (CL+/PS+) reacted strongly with most trophoblasts that were
      freshly isolated (Day 0) and through 2 days of culture, after which time the
      percentage of cells reactive with BA3B5C4 decreased steadily. 3SB9b (CL-/PS+)
      reactivity increased during incubation; about 8% of cells reacted initially, but
      after 1 day of incubation 100% reacted, and this percentage remained stable
      throughout the 4-day incubation. D11A4 (CL+/PS-) reacted only minimally and at
      the level of the negative control monoclonal antibody (mAb) with 1- and 2-day
      cultures. Both mAbs that reacted with PS-dependent antigens completely prevented
      invasion of matrigel-coated filters by isolated trophoblasts. These mAbs also
      inhibited trophoblastic hCG and human PL production by more than 45%. Thus, as
      trophoblasts undergo differentiation, they are reactive with mAbs against PS.
      These antibodies are inhibitory in vitro to trophoblastic hormone production and
      invasion.

PMID- 9002634
TI  - Expression of luteinizing hormone/human chorionic gonadotropin receptor gene in
      benign prostatic hyperplasia and in prostate carcinoma in humans.
AB  - The findings that normal rat prostates express functional LH/hCG receptors led us
      to test the hypothesis that benign prostatic hyperplasia (BPH) and prostate
      carcinomas may also express this receptor gene. The data revealed the presence of
      LH/hCG receptor transcripts and receptor protein in normal and hyperplastic but
      not in atrophic glands present in BPH tissue. Smooth muscle and blood vessels in
      stroma of BPH tissue also contained receptors. Prostate carcinomas contain lower
      and more heterogeneous receptor levels than BPH tissue. Two human prostate cancer
      cell lines (LNCaP and DU 145) that were investigated showed the presence of a
      major 4.5-kilobase transcript and several minor transcripts and also the protein
      of LH/hCG receptors. However, androgen-sensitive LNCaP cells contained more
      receptors than androgen-insensitive DU 145 cells. In summary, we demonstrate for
      the first time that BPH and prostate cancer tissues and cell lines express LH/hCG
      receptor gene. These findings suggest that higher LH levels in aged men may play
      a role in BPH and/or prostate carcinomas.

PMID- 9002633
TI  - C-type natriuretic peptide and the guanylyl cyclase receptors in the rat ovary
      are modulated by the estrous cycle.
AB  - We have previously shown that rat ovaries synthesize atrial natriuretic peptide
      (ANP) and express the cognate guanylyl cyclase (GC-A and GC-B) receptors for ANP.
      Since another natriuretic peptide, termed the C-type natriuretic peptide (CNP),
      can also interact with these receptors, we have investigated whether rat ovaries
      express CNP and if so, whether the concentration of this natriuretic peptide and
      the guanylyl-cyclase receptors are influenced by the estrous cycle. CNP mRNA was
      detected in rat ovaries using a reverse transcription (RT) polymerase chain
      reaction (PCR) strategy. RIA of ovarian extracts, obtained at the individual days
      of the estrous cycle, revealed the presence of immunoreactive CNP. The highest
      levels of CNP were detected at proestrus and were approximately 4-fold higher
      than the levels seen at any other stage of the cycle. GC-A and GC-B receptors
      were detected using quantitative autoradiography after application of either
      [125I]ANP or [125I]-tyr0CNP to sections of frozen ovaries. The highest specific
      binding of each radiolabeled ligand was seen in ovaries from proestrous animals.
      The GC-B receptors were localized to the membrana granulosa of developing ovarian
      follicles. Using quantitative PCR, we determined that levels of GC-A and GC-B
      mRNAs were highest in the ovaries of proestrous animals and were approximately 2-
      to 3-fold higher than the levels seen at diestrus. These findings demonstrate
      that a natriuretic peptide system, consisting of ligands and receptors, is
      present in the rat ovary. Since CNP and the GC receptors show coordinate estrous
      cycle-dependent variation with maximal expression at proestrus, we speculate that
      the natriuretic peptides may play an important role in either the development of
      ovulatory follicles or in the ovulatory process.

PMID- 9002635
TI  - Characterization of the promoter region of the rat testis-specific histone H1t
      gene.
AB  - Histone H1t is synthesized only in male germ cells during the late pachytene
      stage of meiosis and is retained in spermatids until the nucleus elongates.
      Transgenic experiments suggest that spermatocyte-directing sequences lie within
      140 base pairs of the cap site. To study the mechanism of this specificity we
      compared the DNase I footprints made on the immediate promoter regions of H1t and
      H1d (a typical somatic H1) by testis and liver extracts and observed both common
      and differentially protected regions. The common footprints of H1t included an
      Sp1 consensus (GC box 1) and a CCAAT motif. Electrophoretic mobility shift assays
      (EMSA) identified ubiquitous binding factors for GC box 1 and a binding factor
      for the CCAAT element that we identified immunologically as H1TF2. H1t-specific
      footprints occurred over the palindrome CCTAGG and a GC-rich sequence downstream
      of the TATA box (GC box 2). EMSA analysis of the palindrome identified testis
      specific as well as ubiquitous binding factors. UV irradiation of a palindrome
      binding reaction generated a cross-linked doublet of about 50 kDa from both
      testis and liver. Protein factors that bound to the GC box 2 sequence were
      similar from testis and liver, and GC box 1 and an Sp1 consensus competed for
      them. In vitro transcription directed by H1t occurred at comparable levels in
      testis and liver extracts. The importance of both GC box 1 and CCAAT elements was
      demonstrated by deletion analysis and by oligonucleotide competition. No
      dependence on the H1t palindrome was observed for in vitro transcription.

PMID- 9002636
TI  - Role of direct contact between spermatozoa and oviductal epithelial cells in
      maintaining rabbit sperm viability.
AB  - In many species, including the rabbit, spermatozoa attach to the apical plasma
      membrane of oviductal epithelial cells. Attachment to oviductal epithelial cells
      has a beneficial effect on the maintenance of sperm viability during storage in
      the oviduct, but the mechanism by which this occurs is unknown. The present study
      was conducted to determine the role of direct contact between spermatozoa and the
      apical plasma membrane of oviductal cells in maintaining sperm viability. To
      accomplish this, an apical plasma membrane fraction was isolated from homogenized
      rabbit oviducts and kidney (control) by differential precipitation. When viewed
      by electron microscopy, this fraction was composed of closed, roughly spherical
      apical membrane vesicles (AMV) 50-300 nm in diameter. Analysis of anovulatory,
      preovulatory, and periovulatory oviductal AMV by one-dimensional PAGE revealed 19
      major bands. Densitometry revealed quantitative changes in these bands in
      relation to reproductive stage. Rabbit spermatozoa were incubated for 48 h in the
      presence of anovulatory, preovulatory, and periovulatory oviductal AMV. As
      controls, spermatozoa were incubated with rabbit kidney AMV or in defined medium
      (DM) alone. There was no significant (p < 0.05) decline in viability for
      spermatozoa incubated with periovulatory oviductal AMV during the 48-h incubation
      period. In contrast, viability dropped significantly by 12 h for spermatozoa
      incubated with preovulatory and anovulatory oviductal AMV, kidney AMV, or DM
      alone. Periovulatory oviductal AMV were significantly more effective at
      maintaining sperm viability than preovulatory or anovulatory oviductal AMV. Sperm
      viability in the presence of kidney AMV was not significantly different from that
      in DM alone. From these data it can be concluded that direct membrane contact
      between spermatozoa and oviductal epithelial cells plays a role in maintaining
      sperm viability. Furthermore, this effect appears to be tissue specific and
      related to reproductive stage.

PMID- 9002637
TI  - Immunolocalization of receptors for androgen and estrogen in male caprine
      reproductive tissues: unique distribution of estrogen receptors in efferent
      ductule epithelium.
AB  - Androgens and estrogens affect physiological processes in the testis and male
      excurrent duct system. This study was designed to identify and characterize
      distribution of androgen receptors (AR) and estrogen receptors (ER) in the
      reproductive organs of the male goat. Tissues, including testis, efferent
      ductules, epididymis (regions I-V), and ductus deferens, were obtained from five
      mature Nubian goats, fixed in 4% paraformaldehyde, and embedded in paraplast.
      Antigenic sites for AR were unmasked by microwave treatment (four times, 5 min
      each) of tissue sections immersed in 10 mM citrate (pH 6) and were detected using
      the PG-21 rabbit anti-rat/human antibody. Antigenic sites for ER were identified
      using the H-222 rat anti-human monoclonal antibody after tissue sections were
      treated with pronase (0.5 mg/ml, 37 degrees C, 8 min). Avidin-biotin horseradish
      peroxidase procedures were used to identify positive immunoreactivity. Irrelevant
      IgG was substituted for primary antibody in negative controls. Positive nuclear
      immunostaining for AR was observed in all types of epithelial cells, peritubular
      smooth muscle cells, and intertubular fibroblasts of the intratesticular rete,
      efferent ductules, epididymis (regions I-V), and ductus deferens, as well as in
      Sertoli, Leydig, and peritubular myoid cells and intertubular fibroblasts of the
      testis. In contrast, nuclear immunostaining for ER was confined to nonciliated
      cells of the efferent ductules. Thus, AR-positive cells are ubiquitously
      distributed in caprine testicular and excurrent ductular tissues, and ER-positive
      cells are unique to the efferent ductules. The caprine model should be useful in
      studies designed to determine mechanisms through which androgens and estrogens
      regulate development and function of the testes and excurrent ducts.

PMID- 9002638
TI  - Localization of class I and class IV alcohol dehydrogenases in mouse testis and
      epididymis: potential retinol dehydrogenases for endogenous retinoic acid
      synthesis.
AB  - The vitamin A metabolite retinoic acid plays an essential signaling role in
      spermatogenesis by acting as a ligand for nuclear retinoic acid receptors.
      However, little is known about the regulation of retinoic acid synthesis from
      vitamin A (retinol). Here we have examined mouse testis and epididymis for the
      presence of endogenous retinoic acid and for the expression of genes encoding
      class I and class IV alcohol dehydrogenases (ADH), both of which catalyze retinol
      oxidation, the rate-limiting step in the conversion of retinol to retinoic acid.
      Using a bioassay we found that mouse testis and epididymis both have significant
      levels of retinoic acid ranging from 7 to 8 pmol/g, an amount known to be
      sufficient to optimally activate retinoic acid receptors. In situ hybridization
      analysis of mouse testis revealed that class I ADH mRNA was localized in Sertoli
      cells and Leydig cells, while class IV ADH mRNA was confined to late spermatids.
      In the epididymis, class I ADH mRNA was detected in both principal and basal
      cells, whereas class IV ADH mRNA was limited to basal cells. Immunohistochemical
      analyses of testis indicated that class I ADH protein was localized in Sertoli
      and Leydig cells, whereas class IV ADH protein was observed only in late
      spermatids. Class I ADH protein was localized in principal and basal cells of the
      cauda epididymidis but only in basal cells of the caput epididymidis. Class IV
      ADH protein was limited to basal cells along the entire length of the epididymis.
      These results support a role for ADHs during spermatogenesis, potentially as
      retinol dehydrogenases catalyzing local retinoic acid synthesis in the testis and
      epididymis.

PMID- 9002639
TI  - Absence of colony stimulating factor-1 in osteopetrotic (csfmop/csfmop) mice
      disrupts estrous cycles and ovulation.
AB  - Colony stimulating factor-1 (CSF-1) is a hematopoietic growth factor required for
      the recruitment, proliferation, and differentiation of mononuclear phagocytes. In
      addition, CSF-1 is expressed in the female reproductive tract coincident with CSF
      1 receptor localization on preovulatory oocytes, ovarian and uterine macrophages,
      decidual cells, and trophoblast. A role for CSF-1 in female reproduction was
      confirmed by studies on CSF-1-deficient, osteopetrotic (csfmop/csfmop) mice,
      which suffer from low pregnancy rates and smaller litter sizes compared to wild
      type mice. The present study was designed to determine the exact causes of the
      preimplantation fertility defects in these mutant mice. Female csfmop/csfmop mice
      have extended estrous cycles compared to wild-type females, and s.c.
      administration of CSF-1 from birth restores estrous cyclicity. These mice fail to
      display the characteristic proestrous surge in circulating estradiol-17beta.
      However, concentrations of this hormone are normal during the remainder of the
      cycle. Furthermore, csfmop/csfmop females have significantly lower ovulation
      rates than wild-type mice, but the implantation rates of fertilized oocytes are
      normal. Serum pregnancy concentrations of progesterone are also normal in
      csfmop/csfmop females, in line with the relatively normal progression of
      pregnancy in these mice. Thus, the major effect of CSF-1 on female reproductive
      function is on the frequency and rate of ovulation, indicating a major role for
      this growth factor in regulating follicular development and ovulation.

PMID- 9002640
TI  - Adenovirus-mediated gene transfer by perivitelline microinjection of mouse, rat,
      and cow embryos.
AB  - To determine the fate of an episomally expressed transgene, mouse, rat, and cow
      zygotes were injected into the perivitelline space with approximately 100 pl of
      buffer containing the replication-defective human adenovirus, AdCMVLacZ/sub360.
      Viral concentrations ranged from 2.5 to 2.5 x 10(5) plaque-forming units
      (pfu)/100 pl. As viral titer increased, fewer embryos were able to develop to
      blastocysts. In the mouse, the percentage of blastocysts formed ranged from 82%
      in controls to 16% after injection at the highest titer. In the rat and cow, a
      similar decrease in blastocyst formation was noted (62% to 6% and 26% to 4%,
      respectively). Reporter gene (galactosidase, LacZ) activity could be detected in
      mouse embryos after injection at a concentration of only 25 pfu/100 pl, whereas a
      tenfold higher titer was required in the other two species to observe the blue
      LacZ reaction product. When examined after 5 (mouse), 6 (rat), or 9 (cow) days of
      in vitro culture, the proportion of LacZ-positive embryos ranged from 15% to 96%,
      6% to 76%, and 18% to 58% in mouse, rat, and cow embryos, respectively, depending
      upon viral concentration. However, a large percentage of positive embryos proved
      to be expression mosaics, the degree of which was likewise dependent on titer.
      While none of the embryos showed LacZ activity at 30 h after injection, 70% of
      mouse, 8% of rat, and 20% of cow embryos expressed the reporter gene at 42 h.
      Delaying the timing of injection revealed that the efficiency with which mouse
      and rat embryos could be infected decreased with increasing degree of
      differentiation. Only 35% and 18% of mouse embryos expressed the reporter gene
      after injection at the morula or blastocyst stage, respectively. A similar drop
      in efficiency was noted in rat embryos when injections took place at the 8-cell,
      morula, or blastocyst stage, with 70%, 33%, and 9% of embryos, respectively,
      subsequently showing LacZ activity. Likewise, advanced development resulted in a
      decrease in the efficiency of viral-mediated gene transfer in cow embryos, with
      100%, 78%, and 68% of embryos being positive after injection at the 8-cell,
      morula, or blastocyst stage, respectively. These results demonstrate that a human
      adenovirus can be used to express a reporter gene transiently in nonhuman
      embryos.

PMID- 9002641
TI  - Variable expression of cellular retinol- and cellular retinoic acid-binding
      proteins in the rat uterus and ovary during the estrous cycle.
AB  - Ovaries and uteri from normal adult female rats at known stages of the estrous
      cycle were analyzed for the presence of cellular retinol-binding protein (CRBP)
      and both types of cellular retinoic acid-binding protein (CRABP and CRABP II).
      Northern and Western blot analysis of the uteri revealed a peak of CRBP during
      diestrus and a peak of CRABP during proestrus, whereas CRABP II peaked sharply
      during estrus. Immunohistochemical studies showed CRABP II localized to the
      luminal epithelium, while both CRBP and CRABP were observed only in the smooth
      muscle layers of the uterus. In the ovary, CRABP was not detected, while CRBP
      levels remained relatively constant throughout the cycle and CRABP II peaked
      slightly during metestrus. CRBP in the ovary was localized to the oocytes, nearby
      granulosa cells, and some regions of stroma. CRABP II was found predominantly in
      the granulosa cells of mature follicles and early corpora lutea, as well as some
      regions of the stroma. These results suggest a need for further studies to assess
      the role of retinol and its metabolites in normal uterine function and ovarian
      follicular development.

PMID- 9002642
TI  - Energy balance and ovarian follicle development prior to the first ovulation
      postpartum in dairy cows receiving three levels of dietary fat.
AB  - The objectives of this study were to characterize early postpartum (PP)
      follicular development in dairy cows and to evaluate the influence of energy
      balance (EB) and the level of dietary fat on dominant follicle development and
      function. Forty-five multiparous Holstein cows were fed either low (LF, 3.3%),
      moderate (MF, 5.2%), or high (HF, 7.1%) total dietary fat beginning at
      parturition, and daily EB was determined for all cows. Follicular development was
      monitored by ultrasonography, and blood plasma was analyzed for metabolites,
      metabolic hormones, progesterone, estradiol, and FSH. After an increase (p <
      0.01) in mean plasma FSH during Days 1-5, all cows experienced a wave of
      follicular development during the second week PP regardless of diet or EB.
      Feeding the MF (p < 0.05) or HF (p < 0.06) diet resulted in a greater number of
      class IV (> 15 mm) follicles on Day 14 PP as compared to the LF diet. Cows fed
      the MF diet had higher (p < 0.05) peak plasma estradiol during the first
      follicular wave and a shorter (p < 0.05) interval to first ovulation than both LF
      and HF cows. Follicular development prior to first ovulation was characterized by
      either ovulation of the first dominant follicle (OV, n = 19), one or more waves
      of nonovulatory dominant follicles (NOV, n = 18), or the formation of a
      follicular cyst (CYST, n = 8). Ovulation failure during the first follicular wave
      PP was accompanied by lower (p < 0.001) peak plasma estradiol (0.96 +/- 0.36 vs.
      5.0 +/- 0.35 pg/ml), a smaller (p < 0.01) maximum follicle diameter (16.0 +/- 0.9
      vs. 20.0 +/- 1.0 mm), lower (p < 0.09) levels of plasma insulin-like growth
      factor-I (IGF-I; 73.5 +/- 10.1 vs. 102.9 +/- 9.9 ng/ml), and a longer (p < 0.02)
      interval to the EB nadir (14.6 +/- 1.9 vs. 6.4 +/- 1.9 days). The number of days
      to first ovulation was positively correlated with days to the EB nadir (r =
      0.55), with dominant follicles that emerged after the EB nadir exhibiting
      enhanced (p < 0.01) production of estradiol and greater (p < 0.01) ovulatory
      success. The development of large (> 10 mm) dominant follicles was not a limiting
      factor in PP reproductive recovery, and moderate dietary fat shortened the
      interval to first ovulation. Follicular competence early PP was associated with
      higher plasma IGF-I and a shorter interval to the EB nadir.

PMID- 9002643
TI  - Birth of live mice resulting from oocytes fertilized in vitro with cryopreserved
      spermatozoa.
AB  - The objective of this study was to develop a reliable method to cryopreserve
      mouse spermatozoa, using in vitro fertilization (IVF) of oocytes, development of
      resultant zygotes into blastocysts, and the birth of live young after embryo
      transfer as criteria of sperm survival. Epididymal sperm were frozen in a
      raffinose-glycerol solution containing either egg yolk (EY) or BSA. Sperm frozen
      in the presence of EY yielded higher survivals than those frozen in the presence
      of BSA; when used for IVF, the former resulted in more blastocysts (26% vs. 5%).
      Comparison between one-step and stepwise dilution of the cryoprotectant revealed
      no differences in sperm viability as assayed by a vital stain. Nevertheless, IVF
      using frozen sperm recovered by one-step or stepwise dilution resulted in 33% and
      17% blastocyst formation, respectively. When embryos produced with cryopreserved
      sperm were transferred into recipients, pregnancies (12 of 15 recipients) and the
      birth of live young (57 pups from 167 embryos transferred) resulted. These
      results were comparable to those obtained from transferral of embryos produced by
      IVF with fresh sperm (17 pregnancies from 19 recipients, 87 live young from 197
      embryos). Thus, this study has resulted in the development of a simple and
      efficient cryopreservation procedure for mouse sperm.

PMID- 9002644
TI  - Contraceptive effect of sperm-agglutinating monoclonal antibodies in rabbits.
AB  - Immune infertility in humans correlates clinically with the presence of anti
      sperm antibodies that trap (agglutinate) sperm in semen and cervical mucus. To
      test whether sperm-agglutinating antibodies can be effective contraceptive
      agents, several mouse anti-rabbit sperm (MARS) sperm-agglutinating monoclonal
      antibodies (mAbs) were developed that rapidly and completely agglutinate sperm:
      MARS-M3 (IgM), MARS-G16 (IgG3), and MARS-G17 (IgG3). Contraceptive efficacy of
      these mAbs was tested by mixing the mAb with 0.1 ml semen (approximately 1/5 of a
      whole ejaculate) immediately before artificially inseminating rabbits
      paracervically. This paracervical dose of semen provided a rigorous test since it
      delivered several thousand times more fertilizing doses than does a human
      ejaculate. All of the mAbs were contraceptively effective, and MARS-G16 reduced
      the number of fetuses per animal by 88% and 95% with doses of 150 microg and 2
      mg, respectively. The contraceptive efficacy of the MARS mAbs in the rabbit
      suggests that human sperm-agglutinating mAbs may be effective agents for vaginal
      contraception in humans.

PMID- 9002645
TI  - A binding site for steroidogenic factor-1 is part of a complex enhancer that
      mediates expression of the murine gonadotropin-releasing hormone receptor gene.
AB  - Expression of the GnRH receptor (GnRH-R) gene in the anterior pituitary gland, as
      with the genes encoding the gonadotropin subunits, is restricted to gonadotrophs.
      Thus, it is conceivable that a common mechanism is involved in activating cell
      specific expression of these genes. In fact, expression of the alpha- and LHbeta
      subunit genes appears to require binding of the nuclear orphan receptor,
      steroidogenic factor-1 (SF-1). Here we have used DNA protein-binding assays to
      identify a high-affinity binding site for SF-1 in the proximal promoter of the
      murine GnRH-R gene. Southwestern blot analysis using this site as a radiolabeled
      probe revealed binding to a 53-kDa protein in alphaT3-1 cell extracts.
      Furthermore, mutation of this site led to a 58% reduction in promoter activity in
      the gonadotroph-derived alphaT3-1 cell line. Thus, SF-1 may represent at least
      one common pathway for gonadotroph-specific gene expression. In addition, we used
      block-replacement mutagenesis to functionally scan approximately 100 base pairs
      (bp) in a region that we had previously identified as critical for cell-specific
      promoter activity. Mutation of a partial palindrome located at -393 bp relative
      to the start of translation led to a 63% loss of promoter activity. Finally, a
      region containing both the SF-1 binding site and the -393 site was sufficient to
      stimulate cell-specific expression from a heterologous, minimal promoter. Thus,
      we suggest that a complex enhancer that includes a binding site for SF-1 mediates
      cell-specific expression of the GnRH-R gene.

PMID- 9002646
TI  - Absence of natural killer cells during murine pregnancy is associated with
      reproductive compromise in TgE26 mice.
AB  - Strategies of cell depletion were pursued to extend understanding of the
      functions of natural killer (NK) cell-like large granulated lymphocytes found in
      the rodent uterus during pregnancy. Repeated infusions of antibody to Ly-49G2, a
      surface marker thought to be expressed by the progenitor forms of these cells,
      removed Ly-49G2+ cells from the virgin but not the pregnant uterus. Large
      granulated uterine lymphocytes also differentiated during pregnancy in transgenic
      mice that carried a deletion in the IL-2 gene. This cell population was absent in
      two strains of mice, p56lck-/lck-.IL-2Rbeta-/IL-2Rbeta- and TgE26. Implantation
      sites in both of these strains had histopathological anomalies in the zone of
      decidualization. In TgE26 mice, a sudden onset of fetal loss began at Day 10 of
      gestation. Fetal death was associated with progressive changes in the maternal
      uterine arterioles, suggestive of localized arteriosclerosis associated with
      hypertension. TgE26 females carried immune-competent fetuses to term, apparently
      through preventive or compensatory mechanisms that may modify the uterine
      vasculature after the onset of vascular pathology. These studies are the first to
      suggest a vital role for large granulated lymphocytes in the promotion of fetal
      survival and pregnancy success.

PMID- 9002647
TI  - Stage-dependent development of rat 1-cell embryos in a chemically defined medium
      after fertilization in vivo and in vitro.
AB  - The present study was conducted to examine the development of rat 1-cell embryos
      cultured in a chemically defined medium (mR1ECM) soon after penetration of eggs
      in vivo or in vitro. When eggs were recovered from naturally mated females at
      0600-0900 h on the following day, no penetrated eggs with male pronuclei were
      observed. However, the percentage of pronuclear eggs had increased significantly
      at 1000-1100 h (17%) and 1200-1300 h (65%). When penetrated eggs recovered at
      0600-0900 h were cultured in mR1ECM, blastocyst formation (22-46%) was
      significantly less frequent than in those (79-93%) recovered at 1000-1300 h.
      After collection at 0600-0800 h, preculture of penetrated eggs in modified Krebs
      Ringer bicarbonate solution (mKRB) for up to 1200-1300 h improved their
      development to the blastocyst stage from 42% to 78%. Pronuclei were formed in
      almost all (98-100%) of the penetrated eggs examined after 6-20 h of insemination
      in mKRB. When penetrated eggs were transferred from mKRB into mR1ECM after 4-30 h
      of insemination, the percentages (47-64%) of blastocyst formation were
      significantly higher than those (1-20%) for eggs transferred after 1-3 h or after
      40 h of insemination. When a total of 70 morulae or early blastocysts that had
      been produced by in vitro fertilization and developed in vitro were transferred
      to 7 pseudopregnant rats, 5 recipients into which 48 embryos had been transferred
      maintained their pregnancies and 25% of the embryos developed into late fetuses
      or pups. The results of the present study indicate that rat 1-cell embryos
      recovered from oviducts before pronuclear formation, or produced by in vitro
      fertilization, can develop to the blastocyst stage in vitro and that one or more
      factors in mKRB are necessary to maintain their development in mR1ECM.

PMID- 9002648
TI  - Increased bax and interleukin-1beta-converting enzyme messenger ribonucleic acid
      levels coincide with apoptosis in the bovine corpus luteum during structural
      regression.
AB  - Recent reports have demonstrated that prostaglandin F2alpha-induced generation of
      reactive oxygen species or their intermediates inhibits progesterone synthesis
      and may also serve as a trigger for apoptosis in the corpus luteum (CL). BCL-2,
      an inhibitor of apoptosis in a wide variety of cell types, has been reported to
      prevent oxidative stress-induced cell death. Thus, the present studies were
      conducted to determine whether levels of mRNA encoding BCL-2 and related members
      of this gene family (BAX and BCL-Xshort, which induce apoptosis; BCL-Xlong, a BCL
      2 homologue that prevents apoptosis) differed in functional (Day 21 of pregnancy)
      versus regressed (Day 21 of the estrous cycle) CL in the bovine ovary. Levels of
      mRNAs encoding p53, a transcriptional regulator of the bcl-2 and bax genes, and
      interleukin-1beta-converting enzyme (ICE), a protein recently implicated in the
      induction of apoptosis whose expression may be enhanced by oxidative stress, were
      also assessed. Partial cDNA clones encoding bovine bax, bcl-x, p53, and Ice were
      isolated using the reverse transcriptase-polymerase chain reaction (RT-PCR)
      technique with total RNA prepared from functional or regressed CL. A bovine bcl-2
      cDNA could not be isolated from luteal tissue RNA despite the use of several
      primer pairs for amplification. Total RNA was then extracted from functional or
      regressed CL and analyzed by Northern blot analysis. The occurrence of apoptosis
      in regressed CL, as evidenced by the presence of internucleosomal DNA cleavage,
      was associated with a significant increase in both bax and Ice mRNA levels as
      compared with levels of bax and Ice expression in functional CL (p < 0.05, n =
      3). There were no significant differences in bcl-x or p53 mRNA levels in
      functional versus regressed CL. Analysis of bcl-x mRNA by RT-PCR revealed that
      the long form was the primary, if not only, mRNA expressed in functional and
      regressed bovine luteal tissue. On the basis of data that increased expression of
      bax is associated with, and may be required for, apoptosis in ovarian granulosa
      cells and germ cells, we propose that BAX may play a similar role in apoptosis
      induction during luteal regression. Moreover, the increased Ice mRNA levels in
      regressed CL provides the first evidence that the ICE family of death proteases
      may be involved in luteolysis.

PMID- 9002649
TI  - Development of bovine nuclear transfer embryos made with oogonia.
AB  - The pluripotency of embryonic germ cells in the mouse suggests that mitotic
      bovine fetal germ cells might also be a source of pluripotent cells. To
      investigate the pluripotency of bovine oogonia, the development in vitro of
      bovine embryos reconstructed by fusing oogonia with enucleated oocytes was
      compared with that of embryos made similarly with either blastomeres or granulosa
      cells. The donor cells (fresh oogonia, cryopreserved oogonia, 16- to 32-cell
      stage blastomeres, or granulosa cells) were fused to the enucleated oocytes
      electrically. The proportions of reconstructed embryos that had cleaved at 40 h
      after fusion using these types of donor cells were not significantly different
      (37%, 33%, 56%, and 31%, respectively; p > 0.05). However, the proportions of
      cleaved reconstructed embryos that developed to the blastocyst stage were 9%,
      13%, 36%, and 3%, respectively, significantly higher (p < or = 0.05) with
      blastomeres than with the other three types of donor cells. After transfer of 3
      morulae and 4 blastocysts made with oogonia into three recipient heifers,
      embryonic and extra-embryonic tissues developed in one animal. On recovery after
      43 days gestation, this conceptus was shown to be genetically identical, at 11
      microsatellite loci, to the fetus that had provided the oogonia. Cytological
      analysis of the embryos made with oogonia at 40-44 h after fusion and at the
      morula and blastocyst stages revealed that aberrant cytokinesis and nucleokinesis
      had given rise to multinucleated, anucleate, and polyploid cells in the
      reconstructed embryos. It is concluded that limited pluripotency of bovine
      oogonia has been demonstrated, warranting further study in this area.

PMID- 9002650
TI  - Evidence for a local fetal influence on myometrial oxytocin receptors during
      pregnancy in the tammar wallaby (Macropus eugenii).
AB  - Mesotocin (MT), the oxytocin-like peptide of the tammar wallaby (Macropus
      eugenii) is important for delivery of live young. The tammar mesotocin receptor
      (MTR) was first characterized using the iodinated oxytocin receptor antagonist
      [125I]d(CH2)5 [Tyr(Me)2, Tyr4, Orn8, Tyr-NH(2)9]-vasotocin. MTR concentrations
      were then measured in matched samples of gravid and nongravid myometrium and
      median vagina at different stages of the 26-day pregnancy. MTR concentrations in
      both the gravid and nongravid myometrium changed significantly (ANOVA, p < 0.01)
      during pregnancy. There was no difference in MTR concentrations between uteri on
      Days 8-22. From Day 23 of pregnancy, MTR concentrations in the gravid myometrium
      increased (615.8 +/- 144.0 fmol/mg protein), whereas in the nongravid myometrium,
      they remained unchanged (248.6 +/- 65.5 fmol/mg protein). Receptor concentrations
      were high in the gravid myometrium during the last 3 days of pregnancy but
      decreased significantly in the nongravid myometrium. In the median vagina, MTR
      concentrations were low compared with myometrial tissues and did not increase at
      term. Changes in MTR concentrations paralleled changes in uterine responsiveness
      to exogenous MT in vitro. Our data show that MTR concentrations and the
      responsiveness to MT differ between the gravid and nongravid myometrium during
      pregnancy. The increase in MTRs in the gravid myometrium and the decrease in the
      nongravid suggest that different factors influence these receptors in the
      separate uteri, independent of systemic influence.

PMID- 9002652
TI  - Effect of variants of interferon-tau with mutations near the carboxyl terminus on
      luteal life span in sheep.
AB  - Mutant forms of recombinant ovine interferon-tau (oIFN-tau) have been previously
      prepared by site-directed mutagenesis of an ovine gene with the purpose of
      establishing relationships between structure and function of the molecule. These
      mutant forms have altered antiviral and antiproliferative activities, and
      receptor-binding affinities, and their ability to extend estrous cycle length
      after being injected i.m. into nonpregnant ewes has been established. In
      experiment 1, i.m. injection of either PBS (vehicle) alone or with 0.1 mg (n =
      4), 0.5 mg (n = 4), or 2.0 mg (n = 3) of recombinant olFN-tau (S4, identified
      below) was performed twice daily on Days 11-18 postestrus (Day 0 = estrus).
      Luteal life span was extended (p < 0.05) by 4.8 days after injection of 0.5 mg or
      2.0 mg oIFN-tau; injection of 0.1 mg had no effect (p > 0.05) on luteal life span
      relative to the group that received vehicle alone. In subsequent experiments, the
      dosage of oIFN-tau was 1.0 mg per injection twice daily. The objective of
      experiment 2 was to determine the effect of mutated forms of oIFN-tau on luteal
      life span in sheep. Fifty-seven ewes received twice-daily injections (i.m.) from
      Day 10 to Day 20 postestrus of PBS (vehicle) either alone (n = 9), with 0.3
      mg/injection of bacterial contaminating proteins (BP; n = 10), or with 1
      mg/injection of one of the following forms of recombinant oIFN-tau: 1) a fully
      active, 172-amino acid (aa) oIFN-tau (S4, n = 10); 2) a form lacking 11 aa at the
      carboxyl terminus and with an I143-->T mutation (S1), which had very low
      antiviral and antiproliferative activities and receptor-binding affinities (n =
      9); 3) a truncated form identical to S1 but with I143 restored (TRN11), which had
      low antiviral and antiproliferative activities but only slightly reduced receptor
      binding affinities (n = 10); and 4) a form similar to wild type S4 (S4-K) with
      low antiviral and antiproliferative activities but only slightly reduced receptor
      binding affinities (n = 9). Luteal life span was slightly longer (p < 0.05) in
      the TRN11 and S4-K groups (19.6 and 20.6 days, respectively) than in the PBS, BP,
      and S1 groups (16.2, 16.8, and 17.5 days, respectively). In the S4 group, mean
      luteal life span was 33.6 +/- 5.9 days (range 15.5-64 days). A third experiment
      entailing twice-daily injections of either 0.3 mg BP (n = 6), 1 mg TRN11 (n = 5),
      1 mg S4-K (n = 5), or 1 mg S4 (n = 5) was conducted in which the pyrogenic effect
      of the oIFN-tau was also examined. Luteal life span was longer (p < 0.05) in the
      S4-K and S4 groups (18.9 and 28 days, respectively) than in the BP and TRN11
      groups (16.6 and 17.6 days, respectively). Intramuscular injection of all forms
      of IFN-tau caused hyperthermia in ewes initially, but ewes appeared to become
      refractory to treatment after several days. In summary, extension of luteal life
      span was more closely associated with biological activity as assessed in vitro
      than with receptor binding affinities.

PMID- 9002651
TI  - Endocrine activity of induced persistent follicles in sheep.
AB  - This experiment was designed to examine gonadotropin requirements for the
      induction and maintenance of persistent ovarian follicles in sheep. At the time
      of prostaglandin (PG) treatment on the tenth day of an induced estrous cycle, 8
      ewes (with one ovary autotransplanted to the neck) received an injection of a
      GnRH antagonist ([Ac-d-Nal1, d-4-C-1-Phe2, d-Trp3, d-Arg6, d-Ala10] GnRH.HOAc; 50
      microg/kg s.c.), and continuous hourly injections of exogenous ovine LH
      (equivalent to 1.25 microg NIH-oLH-S26) began simultaneously with this first
      antagonist injection (time zero). Antagonist was given three times at 3-day
      intervals. On Day 6, LH injections were stopped in 4 ewes (group 2) but continued
      in 4 other ewes (group 1) until the end of the 10-day experiment. Ovarian vein
      blood was sampled daily every 15 min for a 2-h period around two injections of
      exogenous LH (this sampling included group 2 after Day 6). Additional jugular and
      ovarian vein blood samples were collected every 8 h throughout the experiment.
      Daily ultrasound examination revealed the presence of at least one large follicle
      (range 4- to 7.5-mm diameter) from Day 3 to Day 10 in all ewes, but no new
      growing follicles (> 2 mm) were detected for at least 6 days. After Day 2,
      secretion of estradiol was positively correlated with that of inhibin (r = 0.83,
      p < 0.001), whereas FSH concentrations were inversely related to inhibin (r = 
      0.71, p < 0.001) and estradiol (r = -0.81, p < 0.001). In the absence of an LH
      surge, estradiol and androstenedione secretion (range 5-20 ng steroid/min) was
      maintained from Day 1 to Day 8 in group 1; but in group 2, secretion decreased
      abruptly when the LH injections stopped. Thus, continued low-amplitude, high
      frequency LH pulses were required to maintain estradiol secretion when
      concentrations of FSH were < 0.5 ng/ml. However, estradiol and androstenedione
      secretion decreased (and FSH concentrations increased) between Days 8 and 10 in
      the ewes that received continued LH injections (group 1), showing that atresia in
      estrogenic follicles was not due to a lack of gonadotropin availability but to
      changes within the follicle. For the first 3 days after administration of PG,
      androstenedione secretion was greater than that of estradiol (p < 0.05), but from
      Day 4 to 6 the secretion rates were similar (p < 0.1), suggesting that aromatase
      may be limiting in the first 3 days whereas provision of androstenedione
      precursors was altered as the follicle persisted. In group 2 on Days 7 and 8 when
      hourly LH injections had stopped, neither androstenedione nor estradiol secretion
      increased after one test injection of LH; in contrast, androstenedione but not
      estradiol secretion increased after a second LH test injection 1 h later,
      suggesting that secretion of androstenedione is controlled by repeated exposure
      to LH. In conclusion, persistent estrogenic follicles were produced in the
      follicular phase in sheep by treatment with a combination of GnRH antagonist and
      hourly pulses of LH. Secretion of estradiol was dependent on continued hourly LH
      pulses of approximately 1 ng/ml and the follicles remained estrogenic for 8 days,
      after which time the ability to secrete estradiol and androstenedione declined
      even with continued LH injections.

PMID- 9002653
TI  - Expression and function of a scavenger lipoprotein pathway in porcine luteal
      cells.
AB  - A pathway(s) for uptake of modified (e.g., acetylated, oxidized) low-density
      lipoprotein (LDL) moieties has been recently discovered on luteal cells of
      certain species. The expression and function of this pathway during the life span
      of the corpus luteum (CL) have not been investigated. Aims of the present study
      were the following: 1) to determine whether porcine small and large luteal cells
      take up modified LDL; if so, 2) to compare uptake of native and modified LDL by
      luteal cell subpopulations during the luteal life span and 3) to compare effects
      of native and modified LDL on luteal steroidogenesis during the estrous cycle.
      Collagenase-dispersed luteal cells were prepared from porcine ovaries at various
      stages of the estrous cycle: early (E, Days 4-6), mid (M, Days 8-10), mid-late
      (ML, Day 13-14), or late (L, Day 16-17) (estrus = Day 0). Cells were incubated
      with fluorescent-tagged LDL (Dil-LDL; 0-10 microg/ml) or acetylated LDL (Dil-AC
      LDL; 0-10 microg/ml). Fluorescence was analyzed by multiparameter flow cytometry
      in each of three subpopulations of cells: small (SLC) and large (LLC) luteal
      cells and nonsteroidogenic cells. The percentage of LLC taking up Dil-LDL
      remained relatively constant (65-75%) from E to ML cycle and then declined (13.3
      +/- 4.1%; p < 0.05); these findings were consistent with previous data. In
      contrast, the percentage of LLC taking up Dil-AC-LDL gradually increased from E
      (29.8 +/- 8.5%) to ML (68.3 +/- 5.9%) stage and then declined (17.1 +/- 2.3%; p <
      0.05). Similarly, Dil-LDL uptake by SLC was relatively constant (15-20%) from E
      to M cycle, declining to 2.9 +/- 0.5% at L cycle. Dil-AC-LDL uptake by SLC
      progressively increased from E (5.4 +/- 2.6%) to ML (24.3 +/- 6.9%) and then fell
      somewhat (12.9 +/- 6.7%) in L cycle. Few (< 2%) nonsteroidogenic cells labeled
      for Dil-LDL at all stages, whereas Dil-AC-LDL uptake by nonsteroidogenic cells
      was similar to that by SLC. Dual-uptake experiments revealed subtypes of LLC that
      took up either native LDL only or both native and modified LDL. Progesterone (P4)
      production by E and M luteal cell cultures was dose-dependently increased (p <
      0.05) by both native and modified LDL. In contrast, modified LDL suppressed (up
      to 40-50%, p < 0.05) steroidogenesis by ML and L cultures, whereas LDL had no
      significant effect. Only native LDL stimulated P4 production by isolated SLC,
      although both native and modified LDL similarly increased P4 production by LLC.
      In conclusion, expression of one or more scavenger LDL pathways on porcine luteal
      cell subtypes is dynamic. Moreover, modified LDL can exert both stimulatory and
      inhibitory effects on luteal steroidogenesis in vitro. Differential expression
      and function of a scavenger LDL pathway by subpopulations of cells within the CL
      may play a novel role in luteal development, function, and/or regression.

PMID- 9002654
TI  - Evidence for the requirement of autocrine growth factors for development of mouse
      preimplantation embryos in vitro.
AB  - The mitotic stimuli in the early mammalian embryo have not been unequivocally
      identified. One hypothesis is that the embryo releases autocrine growth factors
      (GFs) that have a role in such growth. To determine whether such putative GFs
      were limited by dilution, and hence secreted, development was observed at various
      embryo concentrations in culture. Embryos were collected at the zygote or 2-cell
      stage. Zygotes were produced by fertilization in situ (ISF) or in vitro (IVF).
      Two-cell-stage embryos had a high rate of development to the blastocyst stage
      across an embryo concentration range of 1/microl-0.001/microl. By contrast,
      zygotes produced by either ISF or IVF were adversely affected by reducing the
      embryo concentration over this range (p < 0.001), with approximately 80% of ISF
      zygotes developing to blastocysts at the highest concentration but only 26% at
      the lowest. For IVF zygotes the corresponding results were 64% and 6%. For all
      three embryo types, the number of cells in each blastocyst was significantly
      lower with reduced embryo concentration. The major determinant of zygote
      development was the concentration of embryos in culture rather than the absolute
      volume of culture medium or the actual number of embryos present. A concentration
      of 1 embryo/microl (in the form of 10 embryos/10microl) gave the best development
      rates and highest cell numbers per blastocyst. Varying the albumin concentration
      influenced development rates; a 10-fold reduction in BSA concentration (to 0.3
      mg/ml) resulted in significantly more IVF zygotes developing to the blastocyst
      stage. Platelet-activating factor (PAF) is released by embryos, and albumin can
      act as a competitive inhibitor of PAF's action on cells. ISF embryos released
      more PAF (p < 0.05) into media than did similarly treated IVF embryos. There was
      no difference in the amount of PAF remaining associated with the resulting 2-cell
      embryos. The amount of PAF released by both these groups was markedly less (p <
      0.001) than the amount released by 2-cell embryos collected fresh from the
      reproductive tract and cultured for 24 h. PAF supplementation of media caused a
      significant increase in the rate of blastocyst development of IVF zygotes at
      embryo concentrations of 0.1/microl (1 ng/ml) and 0.01/microl (100 ng/ml).
      Insulin-like growth factor (IGF)-I (30 ng/ml) and IGF-II (1 ng/ml) also
      stimulated development of IVF zygotes when cultured at an embryo concentration of
      1/10 microl. Epidermal growth factor was without effect over the range 0.2-2000
      ng/ml. Supplementation of media with both PAF and IGF-II gave no additional
      benefit over that caused by IGF-II alone, but this treatment was marginally
      better (p < 0.05) than PAF treatment alone. The results show that factors
      necessary for normal embryo development are diluted to suboptimal levels during
      culture at low embryo concentration. The ability of PAF, IGF-I, and IGF-II to
      partially compensate for the adverse effects of low embryo concentration during
      culture is consistent with their having roles as autocrine embryotrophic factors.
      The use of IVF and low embryo concentrations in culture may provide a functional
      multiple ablation model that will help to define the range of GFs required for
      normal embryo development.

PMID- 9002655
TI  - Maturation, fertilization, and development of marmoset monkey oocytes in vitro.
AB  - This study was conducted to investigate 1) the capacity of in vitro-matured (IVM)
      marmoset oocytes to be fertilized and to support embryonic development in vitro
      and 2) oocyte meiotic maturation in relation to in vivo FSH administration,
      follicle size, and oocyte-cumulus cell status. Pairs of ovaries were collected on
      Day 4 of the follicular phase from adult females receiving either 1) human FSH (3
      IU; n = 5) or 2) control (saline; n = 5) daily for 4 days. Antral follicles were
      excised from ovaries and separated into classes according to size: class 1 (660
      840 microm), class 2 (> 840-1000 microm), class 3 (> 1000-1400 microm), and class
      4 (> 1400 microm). A total of 823 partially naked and cumulus-enclosed oocytes
      (CEOs) were released from follicles and cultured in vitro. Cumulus cells
      remaining after 22 h were removed, metaphase II (MII) oocytes were inseminated
      with epididymal sperm, and resulting embryos were cultured until developmental
      arrest. Fluorescence microscopy was used to assess oocyte meiotic and embryo
      developmental progression. Oocyte germinal vesicle breakdown (GVB)- and MII
      competencies increased significantly with follicular size (p < 0.01 and p <
      0.0001, respectively), although they were independent of oocyte-cumulus cell
      associations. After 24 and 32 h in vitro, 69% and 93%, respectively, of CEOs with
      MII competence had completed meiotic maturation, and the rate of nuclear
      maturation increased progressively with follicle size (p < 0.01) and with the
      association of cumulus cells (p < 0.01). In vivo FSH priming slightly improved
      oocyte GVB- and MII-competencies (p < 0.01 and p < 0.05, respectively) and
      decreased the time required to achieve MII (p < 0.01). IVM oocytes from all
      follicle sizes fertilized (78-92%) in vitro, with 27% developing to morula- and
      4% to blastocyst-stage embryos. This study demonstrates for the first time that
      IVM New World primate oocytes are able to support advanced preimplantation
      embryonic development in vitro. Oocyte meiotic competence and the time course of
      nuclear maturation are profoundly influenced by their follicular origin, and
      marginally by FSH treatment.

PMID- 9002656
TI  - Relationship between androstenedione-induced myometrial contractions and platelet
      activating factor acetylhydrolase in late gestation in pregnant rhesus monkeys.
AB  - An association between platelet-activating factor (PAF) and myometrial
      contractions has been established. Estrogens regulate PAF activity via reduction
      in the activity of plasma PAF acetylhydrolase (PAF-AH), the enzyme that catalyzes
      PAF inactivation. Administration of androstenedione to pregnant monkeys leads to
      sustained increases in maternal plasma estradiol (E2), with persistent nocturnal
      myometrial contractions. The present study tested the hypothesis that
      androstenedione-induced contractions are associated with a fall in maternal
      plasma PAF-AH activity in monkeys. Eight monkeys (132-136 days gestation, dGA)
      were instrumented under halothane anesthesia with maternal vascular catheters and
      uterine electromyogram electrodes. At 138-142 dGA, two baseline maternal arterial
      samples were taken for E2 and PAF-AH measurements. The following day a continuous
      i.v. androstenedione infusion was started in 4 monkeys while 4 control monkeys
      received i.v. infusions of vehicle alone. Arterial blood sampling was repeated 1
      and 3 days after the start of either infusion. Despite an increase in maternal E2
      to term levels and established myometrial contractions, no change in maternal
      plasma PAF-AH activity occurred after androstenedione treatment. Maternal plasma
      E2, PAF-AH activity, and contractions remained unchanged from baseline in control
      monkeys. In conclusion, androstenedione-induced increases in maternal plasma E2
      and myometrial contractions are not associated with a fall in maternal plasma PAF
      AH specific activity.

PMID- 9002657
TI  - Dynamics of maturation-promoting factor and its constituent proteins during in
      vitro maturation of bovine oocytes.
AB  - Maturation-promoting factor (MPF) is known to be a key regulator of both mitotic
      and meiotic cell cycles. MPF is a complex of a B cyclin and the cyclin-dependent
      kinase cdkl (p34cdc2). Oocyte maturation and its arrest at metaphase of meiosis
      II (MII) are regulated by changes in MPF activity. In this study, experiments
      were conducted to examine the dynamics of MPF activity and its constituent
      proteins during in vitro maturation of bovine oocytes. Bovine oocytes displayed
      relatively low levels of MPF (histone H1 kinase) activity at the germinal vesicle
      stage during the first 8 h of maturation. MPF activity increased gradually
      thereafter, and its first peak of activity occurred at 12-14 h of maturation
      (presumptive metaphase I), which was followed by an abrupt reduction in activity
      at 16-18 h, during presumptive anaphase and telophase. MPF activity then
      increased, reaching a plateau at 20-24 h of maturation (MII stage). This high
      level of MPF activity was maintained for several hours but decreased gradually
      after 30 h of maturation and became barely detectable by 48 h of in vitro
      maturation (IVM) culture. At each time point, there was a significant variation
      among individual oocytes in histone H1 kinase activity, which was probably due to
      asynchronous maturation. Abundance of cdk1 increased gradually during the first 8
      h and then remained relatively constant except for an apparent reduction at 18-22
      h of IVM. The level of cyclin B2 increased quickly during the initial 2 h of
      culture, and this high level was maintained until 16 h, after which a significant
      reduction was observed between 18 and 22 h of IVM. The de novo synthesis of
      cyclin B2, however, exhibited a biphasic oscillation during maturation, with
      peaks before the onset of MI and of MII. These results have defined the profiles
      of MPF activity and its individual components during bovine oocyte maturation in
      vitro. We conclude that active MPF regulates bovine oocyte maturation and that de
      novo synthesis of cyclin B2 occurs during the process of maturation.

PMID- 9002658
TI  - Expression of Mos proto-oncoprotein in bovine oocytes during maturation in vitro.
AB  - The c-mos proto-oncogene product Mos is believed to be an active component of the
      cytostatic factor that stabilizes and sustains the activity of maturation
      promoting factor. Mos has been found to be responsible for the metaphase arrest
      of oocytes at the second meiotic division in both Xenopus and the mouse. In this
      study, we have demonstrated, by Western blot and immunoprecipitation analysis,
      that an approximately 39-kDa protein, identified as Mos, was present in in vitro
      matured (metaphase II stage) bovine oocytes but disappeared in
      parthenogenetically activated oocytes. The oocytes actively synthesized p39mos at
      the metaphase II stage (between 22 and 26 h of in vitro maturation [IVM]),
      whereas little p39mos synthesis was detected during the first 4 h of IVM and it
      was nondetectable during aging at 44-48 h of IVM, when oocytes lose the
      capability of normal development after fertilization. Ethanol activation of
      mature oocytes led to the disappearance of p39mos. beta-Tubulin, but not p34cdc2,
      was co-precipitated with Mos when extracts of metaphase II-stage bovine oocytes
      were incubated with Mos antiserum. These results demonstrated that Mos is present
      and actively synthesized in mature bovine oocytes and that oocytes aged beyond
      the optimal time for fertilization seem to lose the ability to synthesize the Mos
      protein. beta-Tubulin was found to be associated with Mos, which suggests a
      possible role for the cytoskeletal protein in maintaining the meiotic arrest in
      mature bovine oocytes.

PMID- 9002660
TI  - Estrogen stimulation of P450 cholesterol side-chain cleavage activity in cultures
      of human placental syncytiotrophoblasts.
AB  - The present study determined whether estrogen has a role in regulating the P450
      cholesterol side-chain cleavage enzyme (P450scc) and/or de novo/deesterification
      cholesterol pathways involved in progesterone biosynthesis within human
      syncytiotrophoblasts. Human placental syncytiotrophoblasts were cultured for 48 h
      with estradiol, and P450scc activity was determined by the formation of
      progesterone from 25-hydroxycholesterol. Estradiol at 10(-7) or 10(-6) M and 25
      hydroxycholesterol increased mean (+/- SE) progesterone production by
      syncytiotrophoblasts (ng/0.5 x 10(6) cells) to a value (19.2 +/- 1.1) that was
      104% (p < 0.001) higher than that of the untreated controls (9.4 +/- 0.8) and 52%
      higher (p < 0.001) than with 25-hydroxycholesterol alone (12.6 +/- 0.9). The
      stimulation of progesterone secretion apparently was not the result of a change
      in progesterone metabolism to its principal metabolite, because 20alpha
      hydroxypregn-4-en-3-one represented a minor secretory component (0.7-1.7 ng/0.5 x
      10(6) cells) under these conditions, and levels were not substantially altered by
      estrogen. In contrast to the stimulatory effect of estradiol on P450scc activity,
      estrogen did not alter either the P450scc mRNA levels or the activities of 3
      hydroxy-3-methylglutaryl coenzyme-A reductase and cholesterol ester hydrolase
      rate-limiting enzymes for the de novo and deesterification pathways,
      respectively, for cholesterol formation in syncytiotrophoblasts in culture.
      Collectively, these results indicate that estrogen regulates the P450scc
      component of the progesterone biosynthetic pathway, which we suggest signals
      functional/biochemical differentiation of syncytiotrophoblasts during primate
      pregnancy.

PMID- 9002659
TI  - A receptor for the oocyte maturation-inducing hormone 17alpha,20beta,21
      trihydroxy-4-pregnen-3-one on ovarian membranes of striped bass.
AB  - Previous studies have shown that blood plasma levels of 17alpha, 20beta-dihydroxy
      4-pregnen-3-one (DHP) and 17alpha, 20beta, 21-trihydroxy-4-pregnen-3-one (20beta
      S) increase in striped bass (Morone saxatilis) undergoing final oocyte maturation
      (FOM). Both hormones are produced by ovarian fragments undergoing hCG-induced
      germinal vesicle breakdown (GVBD) in vitro. In the present study, we investigated
      binding of DHP and 20beta-S to ovarian membranes from striped bass undergoing
      FOM. Saturable binding sites for DHP were not detected. Saturation of 20beta-S
      binding sites with 5 nM [3H]20beta-S occurred within 40 min at 0 degrees C (at 3
      min, half of the maximum specific binding of steroid was calculated to have
      occurred), and the binding was pH-dependent. Scatchard analyses revealed the
      presence of a single class of high-affinity (dissociation constant [Kd] = 1.4 +/-
      0.2 nM), limited-capacity (estimated concentration [Bmax] = 2.7 +/- 0.3 pmol/g
      ovary) 20beta-S binding sites on membranes from striped bass ovaries undergoing
      FOM. In contrast, only low levels of specific binding (Bmax < 0.04 pmol/g tissue)
      were detected on membranes from testes, liver, brain, and muscle. Ovarian
      membranes prepared from vitellogenic females also had low levels (Bmax < 0.1
      pmol/g ovary) of specific 20beta-S binding, less than 5% of that found during
      FOM. Results of competition assays showed that DHP was approximately 250 times
      less effective than 20beta-S for displacing 20beta-S from ovarian membranes. In
      contrast, 20beta, 21-dihydroxy-4-pregnen-3-one was a very effective competitor,
      although it is only a weak inducer of oocyte GVBD in vitro. Of several other
      steroids tested, only progesterone showed affinity for the 20beta-S binding site
      within a physiological range of concentrations. Taken together with previous
      studies of striped bass FOM, these findings indicate that 20beta-S is the oocyte
      maturation-inducing steroid hormone in striped bass.

PMID- 9002661
TI  - Intraoviductal administration of ribonucleic acid from estrogen-treated rats
      mimics the effect of estrogen on ovum transport.
AB  - In order to determine whether or not ovum transport acceleration induced by
      estradiol (E2) requires RNA and protein synthesis in the oviduct, inhibitors of
      RNA and protein synthesis were injected locally in rats treated with E2. We also
      tested whether administration of oviductal RNA from E2-treated rats could mimic
      the effect of E2 on ovum transport. Rats on Day 2 of pregnancy were given a
      single s.c. injection of 10 microg E2 and an intraoviductal (i.o.) injection of
      actinomycin D, alpha-amanitin, or cycloheximide (Chx). In control groups, either
      the steroid or the inhibitor or both were replaced by the respective vehicle. RNA
      obtained from oviduct or ileum of E2-treated rats or from the oviduct of
      propylene glycol-treated rats was injected into the oviducts of recipient rats on
      Day 1 of pregnancy. Animals were autopsied 24 h later to determine the number and
      distribution of eggs in the genital tract. All three inhibitors partially blocked
      the E2-induced ovum transport acceleration, whereas administration of inhibitors
      alone did not affect oviductal egg recovery. Only oviductal RNA obtained from E2
      treated rats decreased the number of oviductal eggs (active extract). To
      interpret this finding, the active extract was preincubated with RNase or DNase
      before i.o. administration. Other groups of recipient rats also treated with
      active extract were injected s.c. with Chx, or their uterine horns were ligated
      to disclose the fate of the missing oviductal eggs. Active extract treated with
      RNase did not decrease the number of oviductal eggs; Chx blocked the effect of
      the active extract; and eggs missing from the oviduct were partially recovered in
      the uteri of ligated recipient rats. It is concluded that protein synthesis in
      the oviduct is required for the full effect of E2 on ovum transport and that one
      or more RNA species induced by E2 in the oviduct are by themselves able to mimic,
      and therefore mediate, the effect of E2 on ovum transport.

PMID- 9002662
TI  - Reduced fecundity in insulin-like growth factor-binding protein-1 transgenic
      mice.
AB  - Transgenic mice that overexpress insulin-like growth factor-binding protein-1
      (IGFBP-1) demonstrate a reduced litter size compared to nontransgenic, wild-type
      mice derived from the same genetic background. To determine the mechanism
      underlying this phenomenon, we examined the number of ovulatory follicles per
      cycle in naturally mated transgenic and wild-type mice by counting the corpora
      lutea and the blastocysts harvested by uterine flushing. In addition, we
      investigated the effects of insulin-like growth factor-I (IGF-I) on blastocyst
      DNA synthesis and examined the effects of a transgenic maternal environment on
      fetal outcome by cross transfer of blastocysts. Significantly fewer corpora lutea
      were observed in ovaries from transgenic vs. wild-type mice (7.6 +/- 1.8 vs. 11.8
      +/- 1.5), and fewer blastocysts were harvested from transgenic mice compared to
      wild-type mice (7.6 +/- 2.3 vs. 10.1 +/- 2.0). DNA content and basal DNA
      synthesis were similar in blastocysts from nontransgenic and transgenic mice.
      However, unlike wild-type blastocysts, transgenic blastocysts did not respond to
      IGF-I with an increase in DNA synthesis. To determine the effects of maternal
      environment on fetal outcome, a mixture of equal numbers of transgenic and
      nontransgenic blastocysts was transferred into foster mothers. The ratio of
      transgenic to nontransgenic pups was not significantly different from the
      theoretically predicted value of 1. However, the litter size was significantly
      reduced in wild-type compared to transgenic foster mothers. These data suggest
      that the reduced fecundity is due to reduced ovulation and blastocyst number.
      Furthermore, expression of the transgene in neither the blastocyst nor the
      maternal tissues had any significant negative effect on implantation or fetal
      wastage.

PMID- 9002663
TI  - The IL-9 receptor gene, located in the Xq/Yq pseudoautosomal region, has an
      autosomal origin, escapes X inactivation and is expressed from the Y.
AB  - All human X-linked genes known so far, except for the Xp/Yp pseudoautosomal
      genes, are conserved as a single linkage group on the murine X chromosome. We
      show that the interleukin-9 (IL-9) receptor gene (IL9R), which is located within
      the human Xq/Yq homology region, maps to the murine chromosome 11. The Xq/Yq
      pseudoautosomal region (Xq PAR) thus represents a second region on the human X
      chromosome which is not X linked in mice. Furthermore, we show that IL9R is
      absent on the Y of great apes. IL9R is thus exceptional among X/Y genes in that
      it is X linked in some mammals, but autosomal or pseudoautosomal in others. Genes
      located on the X and the Y generally escape X inactivation. An exception to this
      rule is SYBL1, a gene located in Xq PAR. SYBL1 is X inactivated and is inactive
      on the Y chromosome. In contrast, we show that IL9R expression does occur from
      the Y, the active and the inactive X chromosomes. This finding raises the
      question of how the transcriptional regulation of genes within Xq PAR occurs and
      how the X inactivation status of IL9R has evolved following the autosome to X and
      the X to X/Y translocation. The evolutionary analysis of the IL9R gene, which is
      located at 10 kb from the telomere, and its pseudogenes at several telomeres,
      also provides insight into the evolution of these loci and of subtelomeric
      regions in general.

PMID- 9002664
TI  - Emergence and scattering of multiple neurofibromatosis (NF1)-related sequences
      during hominoid evolution suggest a process of pericentromeric interchromosomal
      transposition.
AB  - Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase activating
      protein family and is considered to be a tumor suppressor gene. Its very high
      rate of de novo mutation in humans led us to study a specific feature of this
      gene: the presence of numerous NF1-related sequences. According to our results,
      the human genome contains at least 11 NF1-related sequences, nine of which are
      scattered near centromeric sequences of seven different chromosomes. These NF1
      related sequences, whose extent is quite varied according to loci, are
      unprocessed copies of the NF1 gene, and bear numerous mutations. A phylogenetic
      analysis of the six largest sequences indicates that they are all derived from a
      common ancestor, which would have appeared 22-33 million years ago, and was
      subsequently duplicated several times during hominoid evolution. The most recent
      duplication and interchromosomal transposition occurred in the last million years
      suggesting that the process could still be ongoing. Intriguing similarities
      between the evolution of alpha-satellite DNA and NF1-related sequences suggest
      the involvement of a common genetic mechanism for the generation and pericentric
      spreading of these NF1 partial copies.

PMID- 9002665
TI  - Mutations in the gene encoding the inwardly-rectifying renal potassium channel,
      ROMK, cause the antenatal variant of Bartter syndrome: evidence for genetic
      heterogeneity. International Collaborative Study Group for Bartter-like
      Syndromes.
AB  - Inherited renal tubular disorders associated with hypokalemic alkalosis (Bartter
      like syndromes) can be subdivided into at least three clinical phenotypes: (i)
      the hypocalciuric-hypomagnesemic Gitelman variant; (ii) the classic variant; and
      (iii) the antenatal hypercalciuric variant (also termed hyperprostaglandin E
      syndrome). Mutations in the Na-Cl cotransporter (NCCT) underlie the pathogenesis
      of the Gitelman variant and mutations in the Na-K-2Cl cotransporter (NKCC2) have
      recently been identified in the antenatal hypercalciuric variant. We now describe
      mutations in the gene encoding the inwardly-rectifying potassium channel, ROMK,
      in eight kindreds with the antenatal variant of Bartter syndrome. These findings
      indicate that antenatal Bartter syndrome is genetically heterogeneous and provide
      new insights into the molecular pathogenesis of Bartter-like syndromes.

PMID- 9002666
TI  - A newly identified locus for Usher syndrome type I, USH1E, maps to chromosome
      21q21.
AB  - Usher syndrome (USH) is a clinically and genetically heterogeneous disorder
      characterized by congenital hearing loss combined with retinitis pigmentosa. This
      dual sensorineural deficiency is transmitted in an autosomal recessive mode.
      Usher syndrome type I (USH1) is the most severe form. Four loci responsible for
      USH1 (USH1A, 1B, 1C and 1D) have previously been mapped, among which only the
      USH1B gene has been cloned. Using homozygosity mapping in a consanguineous family
      from Morocco, we identified a novel locus for USH1, USH1E, mapping to chromosome
      band 21q21. The delimited 15 cM interval is flanked by the loci D21S1905 and
      D21S1913. Subsequent segregation analysis of two families affected by USH1, in
      which the A, B, C and D loci had been excluded, also excluded the involvement of
      the USH1E locus, therefore indicating the existence of at least one more locus
      for USH1.

PMID- 9002667
TI  - Translation initiation factor eIF-4gamma is encoded by an amplified gene and
      induces an immune response in squamous cell lung carcinoma.
AB  - Amplification of cellular oncogenes is an important mechanism of altered gene
      expression in human cancers. Using comparative genomic hybridization we recently
      identified an amplification at 3q26.1-q26.3 in 30% of squamous cell carcinomas of
      the lung. A variety of methods including microdissection-mediated procedures
      permit cloning of genes encoded within amplified domains but do not directly lead
      to the identification of biologically relevant genes. In this study, we have
      circumvented this problem by combining an immunological and molecular genetic
      approach to analyze squamous cell lung carcinoma. To identify both amplified and
      tumor relevant genes, we generated a cDNA expression library from a tumor with
      the 3q amplification and hybridized the expressed recombinant polypeptides with
      the autologous serum. Of 400000 cDNA clones we identified 17 antigens which
      induce an immune response in a patient with squamous cell lung carcinoma. While
      most clones represent individual genes sequence analysis revealed that four of
      the 17 cDNAs are nearly identical with the eukaryotic translation initiation
      factor (eIF)-4gamma recently assigned on 3q. We demonstrated that the gene for
      eIF-4gamma was amplified within 3q26-q27 in independent squamous cell lung
      carcinomas. In this study, we report the identification of several antigens which
      elicit an immune response in a squamous cell lung carcinoma patient including eIF
      4gamma. eIF-4gamma is encoded by an amplified gene and possibly plays a crucial
      part in the development of squamous cell lung carcinoma.

PMID- 9002668
TI  - Lack of founding Amerindian mitochondrial DNA lineages in extinct aborigines from
      Tierra del Fuego-Patagonia.
AB  - Ancient DNA from bones and teeth of 60 individuals from four extinct human
      populations from Tierra del Fuego-Patagonia (Selknam, Yamana, Kaweskar and
      Aonikenk) has been extracted and the mitochondrial DNA (mtDNA) amplified by using
      the polymerase chain reaction. High-resolution analysis of endonuclease
      restriction site variation in the mtDNA and sequencing of its hypervariable non
      coding control region, revealed complete absence of two of the four primary
      mitochondrial haplotype groups present in contemporary Amerinds, namely A and B.
      In contrast, haplogroups C and D were found in all but one sample with
      frequencies of approximately 38% and 60%. These results, together with the
      decreasing incidence of group A in more southerly latitudes in the American
      continent and the absence of cluster B above 55 degrees North in America and
      Asia, argue that the first settlers entering America 21000-14000 years ago
      already lacked both mtDNA lineages.

PMID- 9002669
TI  - A locus for autosomal dominant posterior polar cataract on chromosome 1p.
AB  - Autosomal dominant congenital cataract is a clinically and genetically
      heterogeneous lens disease. Here we report the linkage of a locus for autosomal
      dominant posterior polar cataract (CPP) to the distal short arm of chromosome 1.
      To map the CPP locus we performed molecular genetic linkage analysis using
      microsatellite markers in a three-generation pedigree. After exclusion of 13
      known loci and candidate lens genes for autosomal dominant cataract, we obtained
      significantly positive LOD scores for markers D1S508 (Z = 3.14, theta = 0) and
      D1S468 (Z = 2.71, theta = 0). Multipoint analysis gave a maximum LOD score of
      3.48 (theta = 0.07) between markers D1S508 and D1S468. From haplotype data,
      however, CPP probably lies in the telomeric interval D1S2845-1pter, which
      includes the locus for the clinically distinct Volkman congenital cataract (CCV).
      This study provides the first evidence for genetic heterogeneity of autosomal
      dominant posterior polar cataract for which a locus had been linked previously to
      chromosome 16q.

PMID- 9002670
TI  - The BRC repeats are conserved in mammalian BRCA2 proteins.
AB  - The breast cancer susceptibility gene BRCA2 encodes a protein of 3418 amino acids
      which does not exhibit substantial sequence similarity to any other protein in
      the public databases. A dot matrix comparison of BRCA2 with itself revealed an
      eight times repeated motif in the segment of the protein encoded by exon 11. As a
      preliminary test of the hypothesis that these motifs are functionally
      significant, we have sequenced exon 11 of BRCA2 in six mammals. An alignment of
      the predicted protein sequences shows that, overall, the motifs have been
      conserved while much of the intervening sequences has diverged. These data
      support the notion that the BRC motifs are important in BRCA2 function. There is,
      however, considerable interspecies variation within certain motif units, raising
      the possibility of redundancy and that not all of the repeats are required for
      the normal function of BRCA2.

PMID- 9002671
TI  - Functional human CFTR produced by stable Chinese hamster ovary cell lines derived
      using yeast artificial chromosomes.
AB  - The cystic fibrosis transmembrane conductance regulator gene (CFTR) encodes a
      transmembrane protein (CFTR) which functions in part as a cyclic adenosine
      monophosphate (cAMP)-regulated chloride channel. CFTR expression is controlled
      temporally and cell specifically by mechanisms that are poorly understood.
      Insight into CFTR regulation could be facilitated by the successful introduction
      of the entire 230 kb human CFTR and adjacent sequences into mammalian cells. To
      this end, we have introduced two different CFTR-containing yeast artificial
      chromosomes (YACs) (320 and 620 kb) into Chinese hamster ovary-K1 (CHO) cells.
      Clonal cell lines containing human CFTR were identified by PCR, and the genetic
      and functional analyses of one clone containing each YAC are described.
      Integration of the human CFTR-containing YACs into the CHO genome at a unique
      site in each cell line was demonstrated by fluorescence in situ hybridization
      (FISH). Southern blot analysis suggested that on the order of one copy of human
      CFTR was integrated per CHO cell genome. Fiber-FISH and restriction analysis
      suggested that CFTR remained grossly intact. Northern analysis showed full
      length, human CFTR mRNA. Immunoprecipitation followed by phosphorylation with
      protein kinase demonstrated mature, glycosylated CFTR. Finally, chloride
      secretion in response to cAMP indicated the functional nature of the human CFTR.
      This study provides several novel results including: (i) functional human CFTR
      can be expressed from these YACs; (ii) CHO cells are a permissive environment for
      expression of human CFTR; (iii) the level of human CFTR expression in CHO cells
      is unexpectedly high given the lack of endogenous CFTR production; and (iv) the
      suggestion by Fiber-FISH of CFTR integrity correlates with functional gene
      expression. These YACs and the cell lines derived from them should be useful
      tools for the study of CFTR expression.

PMID- 9002672
TI  - Comparison of the human and mouse genes encoding the telomeric protein, TRF1:
      chromosomal localization, expression and conserved protein domains.
AB  - Mammalian chromosome ends contain long arrays of TTAGGG repeats that are
      complexed to a telomere specific protein, the TTAGGG repeat binding factor, TRF1.
      Here we describe the characterization of genes encoding the human and mouse TRF1
      proteins, hTRF1 and mTRF1. The mTRF1 cDNA was isolated based on sequence
      similarity to the hTRF1 cDNA and the mTRF1 mRNA was shown to be ubiquitously
      expressed as a single 1.9 kb polyadenylated transcript in mouse somatic tissues.
      High levels of a 2.1 kb transcript were found in testes. In vitro translation of
      the mTRF1 cDNA resulted in a 56 kDa protein that binds to TTAGGG repeat arrays.
      mTRF1 displayed the same sequence specificity as hTRF1, preferring arrays of
      TTAGGG repeats as a binding substrate over TTAGGC and TTGGGG repeats. Expression
      of an epitope-tagged version of mTRF1 showed that the protein is located at the
      ends of murine metaphase chromosomes. In agreement, conceptual translation
      indicated that mTRF1 and hTRF1 are similarly-sized proteins with nearly identical
      C-terminal Myb-related DNA binding motifs. In addition, comparison of the
      predicted mTRF1 and hTRF1 amino acid sequences showed that the acidic nature of
      the N-terminus of TRF1 is conserved and revealed a highly conserved novel domain
      of approximately 200 amino acids in the middle of the proteins. However, other
      regions of the proteins are poorly conserved (<35% identity) and the overall
      level of identity of the mTRF1 and hTRF1 amino acid sequences is only 67%. The
      TRF1 genes are not syntenic; the hTRF1 gene localized to human chromosome 8 band
      q13 while the mTRF1 gene localized to mouse chromosome 17 band E3. The data
      indicate that the genes for mammalian telomeric proteins evolve rapidly.

PMID- 9002673
TI  - Trinucleotide repeats in the human genome: size distributions for all possible
      triplets and detection of expanded disease alleles in a group of Huntington
      disease individuals by the repeat expansion detection method.
AB  - Using a modified Repeat Expansion Detection (RED) assay, that was optimized for
      individual oligonucleotides, unrelated individuals were systematically screened
      for maximal repeat sizes of each of the ten possible trinucleotide repeats.
      Cloned trinucleotide repeats were generated and used as standards for the
      detectability of single copy trinucleotide repeat fragments. When the size
      distributions of trinucleotide repeats were compared to previously reported data,
      significant differences were found for the CTT repeat, which corresponds to the
      expanded GAA repeat in Friedreich ataxia, as well as for ATT, CCT and GTT
      repeats. Since 30-35% of normal individuals have CTG/CAG trinucleotide repeat
      sizes of 180 bp or more, we investigated the question whether small-scale CTG/CAG
      repeat expansions are detectable on a population basis by using the RED
      technique. We blindly screened 20 HD probands with CAG expansions of the HD gene,
      ranging in size between 120 and 174 bp, and found that a shift to larger CAG size
      ranges is clearly detectable when comparing the distribution of maximal repeat
      sizes in the disease group to a control group. Our study, therefore, demonstrates
      that the application of the RED assay to a population of probands and a
      population of controls allows the detection of small-scale CTG/CAG repeat
      expansions in the size range of the expanded HD gene and present in a single
      allele. We also provide standards and control data for the detection of other
      trinucleotide repeat expansions.

PMID- 9002674
TI  - Increased proportion of exon 9 alternatively spliced CFTR transcripts in vas
      deferens compared with nasal epithelial cells.
AB  - CFTR transcripts have been qualitatively and quantitatively analysed in nasal
      epithelial and vas deferens cells by means of reverse transcription PCR.
      Alternative splicing of exon 9, which is known to occur in nasal epithelial
      cells, also occurred in vas deferens cells. The extent of this alternative
      splicing was determined by the allele present at the Tn locus at the end of
      intron 8 of the CFTR gene. However, the proportion of transcripts lacking exon 9
      sequences was increased in vas deferens cells compared with nasal epithelial
      cells, independent of the Tn genotype. We postulate that this tissue specific
      difference in the proportion of CFTR transcripts lacking exon 9 sequences could
      contribute to the tissue specific disease phenotype observed in individuals with
      congenital bilateral absence of the vas deferens.

PMID- 9002675
TI  - Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex
      reversal: lack of genotype/phenotype correlations.
AB  - It has previously been shown that, in the heterozygous state, mutations in the
      SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY
      sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation
      were characterized in one SOX9 allele each, and in one case, no mutation was
      found. Four missense mutations are all located within the high mobility group
      (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant
      SOX9 proteins. Among the five nonsense and three frameshift mutations identified,
      two leave the C-terminal transactivation (TA) domain encompassing residues 402
      509 of SOX9 partly or almost completely intact. When tested in cell transfection
      experiments, the recurrent nonsense mutation Y440X, found in two patients who
      survived for four and more than 9 years, respectively, exhibits some residual
      transactivation ability. In contrast, a frameshift mutation extending the protein
      by 70 residues at codon 507, found in a patient who died shortly after birth,
      showed no transactivation. This is apparently due to instability of the mutant
      SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and
      nonsense mutations are found in patients with and without XY sex reversal,
      indicating that sex reversal in CD is subject to variable penetrance. Finally,
      none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an
      altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9
      mutations do not usually result in XY sex reversal without skeletal
      malformations.

PMID- 9002676
TI  - Quantification, by solid-phase minisequencing, of the telomeric and centromeric
      copies of the survival motor neuron gene in families with spinal muscular
      atrophy.
AB  - In an analysis of 30 families affected by spinal muscular atrophy (SMA) we have
      used the solid-phase minisequencing method to determine the ratio between the
      number of telomeric and centromeric copies of the survival motor neuron gene (SMN
      and cBCD541 respectively) on normal and SMA chromosomes. This has enabled us to
      establish haplotypes with regard to SMN and cBCD541, and estimate their
      frequencies, on both types of chromosomes. Six predominant haplotypes were
      identified, three for normal chromosomes and three for SMA chromosomes,
      characterized by having 0, 1, or 2 copies, respectively, of cBCD541. We found
      evidence for the presence of patients homozygous for a deletion of SMN and with
      only one copy of cBCD541, but found none deleted for all copies of this gene.
      Several asymptomatic carriers of SMA with only a single copy of SMN and no copy
      of cBCD541 were identified. We could not confirm the hypothesis that the presence
      of more copies of cBCD541 is correlated to a less severe course of the disease.
      The frequencies of haplotypes characterized by having 0, 1, or 2 copies,
      respectively, of cBCD541 were found to differ significantly between normal and
      SMA chromosomes. This distribution can be explained by an underrepresentation of
      the haplotype completely lacking SMN genes, which is expected to cause early
      embryonic death in homozygotes. This first report of a direct haplotype analysis
      of SMN and cBCD541 should help clarify the role of cBCD541 in the pathogenesis of
      SMA.

PMID- 9002677
TI  - Cancer risk associated with germline DNA mismatch repair gene mutations.
AB  - The autosomal dominant syndrome of Hereditary Nonpolyposis Colorectal Cancer
      (HNPCC) is due to germline DNA mismatch repair gene mutations in most cases.
      However, the penetrance of such mutations outwith classical HNPCC kindreds is
      unknown because families studied to date have been specifically selected for
      research purposes. Using a population-based strategy, we have calculated the
      lifetime cancer risk associated with germline DNA mismatch repair gene mutations,
      irrespective of their family history. We identified 67 gene carriers whose risk
      to age 70 for all cancers was 91% for males and 69% for females. The risk of
      developing colorectal cancer was significantly greater for males than for females
      (74% versus 30%, P= 0.006). The risk of uterine cancer (42%) exceeded that for
      colorectal cancer in females, emphasising the need for uterine screening. Our
      findings give further insight into the biological effect of defective DNA
      mismatch repair. We have demonstrated a systematic approach to identifying
      individuals at high risk of cancer but who may not be part of classical HNPCC
      families. The risk estimates derived from these analyses provide a rational basis
      on which to guide genetic counselling and to tailor clinical surveillance.

PMID- 9002678
TI  - Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome
      type IB.
AB  - Usher syndrome is recognized as the most frequent cause of hereditary deaf
      blindness. Usher syndrome type I (USH1), the most severe form of the disease, is
      characterized by profound congenital sensorineural deafness, constant vestibular
      dysfunction, and retinitis pigmentosa of prepubertal onset. This form is
      genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar.
      However, only the gene responsible for USH1 B (which accounts for approximately
      75% of USH1 cases) has been characterized. It encodes a long-tailed
      unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence.
      Primers covering the complete myosin VIIA coding sequence as well as the 3' non
      coding sequence were designed, allowing direct sequence analysis of each of the
      48 coding exons and flanking splice sites in seven patients affected by USH1.
      Four novel mutations were thereby identified. The possibility should now be
      considered of a sequence-based prenatal diagnosis in some of the families
      affected by this very severe form of Usher syndrome.

PMID- 9002679
TI  - Identification of a complex congenital heart defect susceptibility locus by using
      DNA pooling and shared segment analysis.
AB  - The identification of genetic loci involved in most forms of congenital heart
      disease has been hampered by the complex inheritance patterns of these disorders.
      Atrioventricular canal defects (AVCDs) are most commonly associated with Down
      syndrome, although non-syndromic cases also occur. Non-syndromic AVCDs have been
      attributed to multifactorial inheritance. However, the occurrence of a few
      kindreds with multiple affected individuals has suggested that a major genetic
      locus can account for the disorder in some families. We have used a combination
      of DNA pooling and shared segment analysis to perform a high density screen of
      the entire autosomal human genome in an extended kindred. In so doing, we have
      identified a genetic locus on chromosome 1 shared by all affected individuals.
      Our data demonstrate the existence of a congenital heart defect susceptibility
      gene, inherited as an autosomal dominant with incomplete penetrance, involved in
      AVCD. Furthermore, our data demonstrate the power of using key isolated kindreds
      in combination with high density genomic screens to identify loci involved in
      complex disorders such as congenital heart defects.

PMID- 9002680
TI  - Localization of a gene for oculodentodigital syndrome to human chromosome 6q22
      q24.
AB  - Oculodentodigital syndrome (ODD) is a congenital, autosomal dominant disorder
      which affects the development of the face, eyes, limbs and dentition. Spastic
      paraparesis is thought to be an occasional manifestation of the disorder. Type
      III syndactyly, which occurs as part of ODD, has also been reported to occur as
      an isolated entity. In the current investigation, a total genome search for the
      location of the ODD locus was instigated and linkage to polymorphic markers
      located on chromosome 6q established (pairwise Zmax = 9.37; theta = 0.001).
      Analysis of a large family with type III syndactyly, but atypical facial
      features, further suggested that isolated type III syndactyly is also located in
      this same region of the genome.

PMID- 9002681
TI  - Somatic mutation processes at a human minisatellite.
AB  - Germline instability at human minisatellites frequently involves complex inter
      allelic transfers of repeat units usually restricted to one end of the repeat
      array and apparently regulated by flanking DNA. In contrast, nothing is known
      about the structural basis of somatic instability at minisatellites. An
      electrophoretic size-enrichment strategy was therefore developed at minisatellite
      MS32 (D1S8) to enable rare abnormal-length mutants to be detected, validated and
      quantitated in blood DNA by single molecule PCR. Structural analysis of rare
      mutant alleles in blood revealed simple deletions/duplications of repeat unit
      blocks located at random along the tandem repeat array, a mode of mutation
      completely different from that seen in sperm. Furthermore, allele-specific
      suppression of sperm instability at MS32 did not affect somatic instability.
      These data suggest that conversion-based minisatellite mutation in sperm is
      completely germline-specific and most likely meiotic in origin. Somatic
      instability appears to occur by a separate pathway involving replication slippage
      or, more likely, intra-allelic unequal crossing over.

PMID- 9002682
TI  - Genotype-phenotype correlation for nucleotide substitutions in the IgII-IgIII
      linker of FGFR2.
AB  - Dominantly acting, allelic mutations of the fibroblast growth factor receptor 2
      (FGFR2) gene have been described in five craniosynostosis syndromes. In Apert
      syndrome, characterised by syndactyly of the hands and feet, recurrent mutations
      of a serine-proline dipeptide (either Ser252Trp or Pro253Arg) in the linker
      between the IgII and IgIII extracellular immunoglobulin-like domains, have been
      documented in more than 160 unrelated individuals. We have identified three novel
      mutations of this dipeptide, associated with distinct phenotypes. A C-->T
      mutation that predicts a Ser252Leu substitution, ascertained in a boy with mild
      Crouzon syndrome (craniosynostosis with normal limbs) is also present in three
      clinically normal members of his family. A CG-->TT mutation that predicts a
      Ser252Phe substitution results in a phenotype consistent with Apert syndrome.
      Finally, a CGC-->TCT mutation that predicts a double amino acid substitution
      (Ser252Phe and Pro253Ser) causes a Pfeiffer syndrome variant with mild
      craniosynostosis, broad thumbs and big toes, fixed extension of several digits,
      and only minimal cutaneous syndactyly. The observation that the Ser252Phe
      mutation causes Apert syndrome, whereas the other single or double substitutions
      are associated with milder or normal phenotypes, highlights the exquisitely
      specific molecular pathogenesis of the limb and craniofacial abnormalities
      associated with Apert syndrome. Ser252Phe is the first noncanonical mutation to
      be identified in this disorder, its rarity being explained by the requirement for
      two residues of the serine codon to be mutated. The description of independent,
      complex nucleotide substitutions involving identical nucleotides is
      unprecedented, and we speculate that this may result from functional selection of
      FGFR mutations in sperm.

PMID- 9002683
TI  - The Human Genome Project: issues and ethics.

PMID- 9002684
TI  - The REST regimen: an individualized nursing intervention for infant irritability.

PMID- 9002685
TI  - Current treatment options for ectopic pregnancy.

PMID- 9002686
TI  - When a syncopal event is more than a faint, Part I.

PMID- 9002687
TI  - Assisted suicide or the right to die, Part I.

PMID- 9002688
TI  - An educational program for cuddlers.

PMID- 9002690
TI  - Methods for assessing the accuracy of measuring instruments, Part II.

PMID- 9002689
TI  - Stick to life: a sticker competition for smoking prevention.

PMID- 9002691
TI  - Ketorolac: an alternative for the management of acute pain.

PMID- 9002692
TI  - New tools for combat casualty care.

PMID- 9002693
TI  - Management training, the sooner the better.

PMID- 9002694
TI  - Doxycycline vs. mefloquine.

PMID- 9002695
TI  - Al Eskan disease: Persian Gulf syndrome.
AB  - This article examines the potential relationship between Al Eskan disease and the
      Persian Gulf syndrome. Al Eskan disease, reported in Military Medicine in 1992,
      is a novel and previously unreported condition triggered by the exceptionally
      fine sand dust of the Central and Eastern Saudi Arabian peninsula. We repeat our
      study of the pathogenesis of Al Eskan disease to include the ultrastructural and
      microanalytical study of the sand, aerobiological studies of the Kingdom of Saudi
      Arabia, and the etiology, symptoms, and prevalence of the disease. We conclude
      that immunodepression resulting from the continued presence of sand particles
      less than 1 micron in diameter in the lungs and bodies of Persian Gulf veterans
      explains not only the symptoms of the hyperegic lung condition of phase I and the
      symptoms of phase II of Al Eskan disease, but also provides an important clue to
      a common factor in most cases of Persian Gulf illnesses. We include a discussion
      of most of the commonly suspected agents in the Persian Gulf syndrome. In this
      case, we conclude that each of these factors, such as oil well fires, old-world
      diseases, or depleted uranium, are probably adjuvant or contributing causes. The
      only common exposure that would lead to recognition of the Persian Gulf syndrome
      as a single medical condition, rather than a catch-all phrase for unrelated
      conditions, appears to be exposure to the ubiquitous, fine sand of the area, and
      a resulting immunosuppression that is aggravated by opportunistic infections and
      other nonmicrobial ailments.

PMID- 9002696
TI  - Suicide among military conscripts in Finland: a psychological autopsy study.
AB  - This study describes suicides during compulsory military service and compares
      them with other young male suicides as part of a nationwide psychological autopsy
      study of all suicides in Finland during a single year. The victims' relatives and
      attending health care personnel were interviewed, and data from records were
      collected. Five of the seven conscript suicides had a depressive syndrome, often
      of short duration. Two victims previously had suicidal thoughts or attempted
      suicide. The most common suicide method was with firearms. Compared with other
      young male suicides, physical illness in conjunction with a psychiatric diagnosis
      was less common in the conscript victims. Civilian male suicides tended to have
      more substance abuse and more severe psychological impairment. They also
      committed suicide under the influence of alcohol more often than conscripts.
      Interpersonal separation was more often the precipitating event of the suicide
      among the conscripts than among the other suicides. Conscripts should be
      encouraged to utilize health and social services when they have psychosocial
      problems or even minor psychiatric symptoms.

PMID- 9002697
TI  - Clinical assessment and arteriography for patients with penetrating extremity
      injuries: a review of 500 cases with the Veterans Affairs West Side Medical
      Center.
AB  - For patients suspected of having arterial injuries form penetrating trauma to the
      extremities, the decision to perform arteriography should be based on clinical
      criteria rather than "proximity" alone. In order to demonstrate the increased
      yield of arteriography resulting from appropriate patient selection, we reviewed
      the results of 500 arteriograms performed at the West Side Veterans Affairs
      Medical Center to exclude arterial injuries in symptomatic patients following
      penetrating trauma to their extremities. According to their clinical
      presentation, the patients were grouped into three different screening categories
      A, B, and C, which correspond respectively to "mild," "soft," and "hard" clinical
      signs and symptoms suggestive of arterial injury. All symptomatic patients
      injured by shotgun were included in category C due to the weapon's destructive
      power. The majority (318/500, 63.6%) of the 500 arteriograms were positive, and
      102 of the positive studies identified major injuries that required surgical
      intervention. The remaining 216 identified injuries were minor or self-limiting.
      Increasing incidence of major injuries was found when comparing patients with
      mild (1.22%), soft (27.8%), and hard (60.0%) clinical signs and symptoms of
      arterial injury. These result suggest that arteriography, when combined with
      appropriate patient selection based on clinical examination, would be most
      effective in finding significant arterial injuries.

PMID- 9002699
TI  - Review of the transmucosal drug delivery.
AB  - The epithelial barriers limits the quantity of drug that can be delivered by a
      topical route for either local or systemic treatment. Any chemical that can help
      to reversibly minimize the epithelial barriers would improve drug uptake.
      Permeabilizers are such chemicals, and their mode of action generally involves
      fluidization of the intracellular lipid in the epithelial barrier. The vehicle in
      which the permeabilizers is delivered is equally important and needs to be
      specifically tailored to the solubility properties of the drug. Therefore, the
      selection of the appropriate permeabilizer and vehicle can make the delivery of
      medication across the oral mucosa a feasible option.

PMID- 9002698
TI  - The trimodal death distribution of trauma victims: military experience from the
      Lebanon War.
AB  - INTRODUCTION: Mortality in war is traditionally divided into two categories:
      killed in action and died of wounds. Mortality in civilian trauma is generally
      divided into three categories: immediate death (50%), early death (30%), and late
      death (20%). Can we identify a trimodal death distribution among war victims?
      METHODS: We analyzed data for casualties in the Lebanon War from June 6 to
      September 20, 1982. During this period a total of 1,950 soldiers were injured;
      351 (18%) of them died. Time of injury and time of death of the victims was
      determined from real-time recordings during the battle and from hospital files.
      RESULTS: Analyzing the time of death revealed that 329 of the soldiers (93.7%)
      died within the first hour after injury, 7 soldiers died 1 to 4 hours after
      injury (2%), and 15 soldiers died 24 hours to 75 days after injury (4.3%). The
      most common causes of death during the first hour after injury were central
      nervous system (CNS) injuries 31%, exsanguination 30%, incineration 21%, and
      combined CNS injury and exsanguination 10.9%. Exsanguination was the leading
      cause of death 1 to 4 hours after injury (86%). CNS injury was the most common
      cause of late death (60%). Only 1.1% of the soldiers who reached the hospital
      alive died of their wounds. CONCLUSIONS: A trimodal mortality distribution with
      different causes of death in each peak can be identified in the mortality pattern
      of Israeli soldiers during the Lebanon War. The relative height of the different
      peaks and the causes of death in the third peak are different from those found in
      civilian trauma. We believe that prompt medical treatment and expeditious
      evacuation from the battle zone led to a very low death rate among the wounded
      soldiers who had reached the hospital alive. The same factors may have increased
      the relative portion of CNS injuries as a cause of late death.

PMID- 9002700
TI  - The establishment of the Croatian Dental Crops: the front-line experience of a
      dentist volunteer.
AB  - The establishment of the first dental office of the Croatian Dental Corps (CDC)
      in the city of Zadar represented at the same time the beginning of the CDC. This
      article describes the front-line experience of a dentist who volunteered to
      provide basic medical help, which eventually laid the groundwork for providing
      general dental care and establishing the first CDC dental office. The office was
      opened on December 16, 1991, and provided general dental care except prosthetics.
      Although faced with numerous problems and extremely difficult conditions, the
      office staff completed 1,913 initial and 1,157 control checkups and performed
      4,002 services by treating 12 to 16 patients per day. The main causes for
      emergencies were caries (59%) and endodontic complications (28%). This variety of
      services in the proximity of the front line is considered extensive even for
      advanced medical corps of modern armies.

PMID- 9002702
TI  - Preventive mental health interventions in peacekeeping missions to Somalia and
      Haiti.
AB  - Mental health interventions of the 528th Combat Stress Control unit to limit the
      numbers of psychiatric casualties on recent peacekeeping missions are discussed.
      Similarities and differences in the mental health support of Operation Restore
      Hope (Somalia) and Operation Uphold Democracy (Haiti) are reviewed. The mission
      to Somalia was marked by unexpected combat casualties. The mission to Haiti was
      marked by unexpected self-inflected casualties. Lessons learned by mental health
      officers serving on these missions are discussed. Recommendations for prevention
      of psychiatric casualties on future missions are presented.

PMID- 9002701
TI  - Medical support to a nonprofessional brigade during the Croatian Operation Storm.
AB  - A review and description is presented of medical support in the nonprofessional
      Croatian Home Guard brigade (2,200 soldiers) during the Croatian Operation Storm.
      Medical support was organized according to a straightforward and easily
      changeable model that enabled quick adaptations from defense to attack positions.
      It was provided initially on the front line by company reception units. Further
      support included battalion aid stations, brigade clearing stations, and the
      clinical Hospital (fourth echelon) in the nearby city. The brigade medical corps
      was all volunteers; 9 medical doctors (two women) and 20 medical technicians and
      nurses. Medical corps assets included a mobile surgical team, eight ambulance
      vehicles, two spare vehicles, and one helicopter. After one 3-day action, brigade
      losses were 3 dead, 31 wounded (14 with firearms), and 2 diseased. According to
      the available data, enemy losses were 25 dead, 4 wounded, 2 sick soldiers, and 48
      captured. Transportation time from the battlefield to the hospital was between 60
      and 75 minutes. There were no deceased (including enemy soldiers) because of
      insufficient medical support and/or transportation problems. The applied model of
      medical corps organization, elaborate preparations, good training, and excellent
      motivation had a major role in successful treatment of war casualties.

PMID- 9002703
TI  - Case management in psychiatric inpatient recapture.
AB  - A 2-year reduction of $5.25 million in inpatient costs, representing a decrease
      of 74%, resulted from implementation of a Psychiatric Management Initiative at
      Munson Army Community Hospital. Case management was a major component. Management
      in the military Civilian Health and Medical Program of the Uniformed Services
      (CHAMPUS) system has major differences from the civilian sector. The military
      case manager functions as a "guest" in the civilian psychiatric hospitals with no
      authority to direct care. The practice involves trend analysis, team work,
      innovative treatment alternatives, and active discharge planning with follow-up.
      This program was successful in the recapture of CHAMPUS costs despite constraints
      by CHAMPUS regulations. Costs went from $3,555,285 in fiscal year 1993 down to
      $600,743 in fiscal year 1995.

PMID- 9002704
TI  - Serum creatine kinase kinetics after endomyocardial biopsy in cardiac transplant
      patients.
AB  - The objective of this study was to define the changes in serum creatine kinase
      (CK) and creatine kinase-MB isoenzyme (CK-MB) activities following endomyocardial
      biopsy. Ten cardiac transplant recipients underwent routine surveillance
      endomyocardial biopsy via the right internal jugular vein with single-use
      disposable bioptomes. Serum CK and CK-MB levels were measured at baseline and
      post-biopsy at 15, 30, and 45 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16, 20, and 24
      hours. There was no significant increase in serum total CK after biopsy. No
      measurable change in CK-MB was observed in 40% of patients. CK-MB increased
      significantly in the remaining patients (N = 6) at 30 minutes (p < 0.05), and
      continued to rise to a peak at 4 hours post-biopsy, after which CK-MB gradually
      decreased to baseline. However, the increase in CK-MB did not meet criteria for
      the diagnosis of myocardial necrosis, hence should not be confused with the
      change in CK-MB occurring with myocardial infarction. These findings suggest that
      serum CK-MB activity is useful in the differential diagnosis of chest pain in
      cardiac transplant patients in the setting of recent biopsy.

PMID- 9002705
TI  - Preventing heat injury: military versus civilian perspective.
AB  - Guidelines for preventing heat injury (HI) among military personnel are not
      directly applicable to civilian personnel. Military guidelines call for
      relatively large volumes of prophylactic water consumption and physical activity
      limitations depending on the wet bulb globe temperature. However, in civilian
      populations, there is an increased prevalence of HI risk factors: older age,
      medication use, especially anticholinergic and psychotropic medications, obesity,
      previous HI, and skin disorders. Although dehydration is a major contributor to
      HI in military situations, it is unlikely in classical heat stroke among
      civilians. Civilian guidelines are based on the heat index. Activity levels must
      be restricted more for civilians, and prophylactic water consumption (beyond
      replacing loss from sweat) is not necessary. This review discusses the
      pathophysiology of heat injury, contrasts the military and civilian approach to
      prevention of HI, and describes appropriate field intervention for HI.

PMID- 9002706
TI  - Periodontal indices of patients taking isoniazid and rifampin: a pilot study.
AB  - A significant reduction in the incidence of tuberculosis (TB) has resulted from
      the use of medications such as isoniazid (INH) and rifampin. Unfortunately, there
      has been a resurgence of TB since the mid 1980s. The purpose of this pilot study
      was to evaluate the effects of INH and rifampin on periodontal indices of
      patients with positive tuberculin skin tests (PPD). The gingival index, plaque
      index, and periodontal scoring and recording were recorded in PPD-positive
      patients at baseline and 1 month. Control patients received no medications during
      the study and were evaluated at baseline and 1 month. Mean values for each
      patient were obtained and analyzed using unpaired t tests (N = 8). Statistically,
      within the limits of this study, it was found that patients taking INH and/or
      rifampin had a significant decreased (p < 0.05) in gingival inflammation from
      baseline.

PMID- 9002708
TI  - Initial success and substantial government savings may mandate prime vendor
      contracts for Table of Organization and Equipment units and development support.
AB  - In November 1994, the Department of Pharmacy at Madigan Army Medical Center and
      the 62nd Medical Group Logistics (Fort Lewis, Washington) examined the
      feasibility of prime vendor support for the 18th Mobile Army Surgical Hospital in
      a Table of Organization and Equipment (TOE) unit rapid deployment. The TOE
      medication list was deemed to be out of date and a state-of-the-art formulary was
      developed. By identifying three National Drug Code bioequivalent substitutes for
      each National Stock Number, a 94% prime vendor match was achieved for
      pharmaceuticals form the new formulary serving as our template. The 6% of
      medications that were not able to be matched consisted of items deemed as
      military-unique or items not covered by the prime vendor government contracts
      with wholesalers. On August 7, 1995, a trial was conducted to determine whether
      the local prime vendor had the capacity to support a deployment under its present
      contract with Madigan Army Medical Center. Two hundred eighty-six line items were
      ordered, mocking the deployment of two medical units. More than 95% of the line
      items were filled within 5 days from the local prime vendor. Under the local
      contract, the prime vendor was under no obligation to have out-of-stock
      medications provided by overnight shipment from other national distribution
      sites. This advantage, which is standard in national pharmaceutical prime vendor
      contracts negotiated by large civilian group purchasing organizations, would have
      substantially decreased the period of time to attain a > 95% fill. The results of
      this trial have provided strong support for prime vendor utilization in future
      deployments.

PMID- 9002707
TI  - Soldier performance and strenuous road marching: influence of load mass and load
      distribution.
AB  - Fifteen male soldiers performed six maximal-effort, 20-km road marchers. They
      carried load masses of 34, 48, and 61 kg, using a standard military backpack with
      frame or an experimental doublepack. March times decreased as mass increased and
      were faster with the standard pack than with the double-pack. The doublepack
      resulted in less low back discomfort and a lower incidence of blisters at the
      highest load, but also resulted in more discomfort in the neck and hips. Neither
      load mass nor pack type affected soldiers' marksmanship ability, grenade throw
      accuracy, or cognitive ability. The maximal-effort march itself affected the
      marksmanship tasks by increasing the post-march vertical shot group dispersion.
      The concept of distributing the load mass more evenly around the center of mass
      of the body has both positive and negative aspects and warrants further
      investigation.

PMID- 9002709
TI  - Implementing a formal cytotoxic agent program at an overseas medical treatment
      facility.
AB  - United States Naval Hospital (USNH), Okinawa, Japan, is the Navy's largest
      outside continental U.S. hospital, with 104 inpatient beds. An historical vision
      for the hospital has been to become the military's medical referral center for
      the Western Pacific. In keeping with this version the hospital has sought to
      expand, upgrade, or initiate certain health care services. One service that has
      been pursued over the last decade has been implementation of a formal cytotoxic
      agent program. This was finally accomplished in August 1995 with the signing by
      the Commanding Officer of USNH Okinawa Instruction 6570.1. The purpose of this
      paper is to explain how the program was implemented; described the services of
      the program sought to provide; discuss the key players involved with the
      implementation process; describe hindrances to program implementation; and,
      finally, to describe USNH Okinawa's experience with the program.

PMID- 9002710
TI  - [Candidiasis of the oropharyngeal mucosa. The clinical and epidemiological
      aspects in a group of HIV-positive and AIDS patients].
AB  - Immune system deficiencies, particularly cell-mediated immunity are the main
      events of HIV infection. The resulting syndrome is removies: AIDS. This immune
      deficiency encourages neoplasms such as the Kaposi sarcoma and non Hodgkin
      lymphoma, above all, it explains the reason why infections supported by
      opportunist germs, normally not pathogenic for immuno-competent people, are the
      main reason for morbidity and mortality in this kind of patients. Since among
      mycotic infections, the main one in these patients is candidiasis, particularly
      oro-pharyngeal candidiasis, we have carried out a research with the aim of
      evaluating the main mucosae oris pathologies in HIV and AIDS patients and, among
      them, the most directly correlated to HIV infection with reference to oro
      pharyngeal candidiasis. We have based our research on the analysis of 237
      patients case-histories. From January 1993 to December 1994 these patients have
      been examined at the Odontological Surgery by the "Centro San Luigi" for HIV
      correlated pathologies researches and treatments (Istituto Scientifico Ospedale
      San Raffaele-Milano.

PMID- 9002711
TI  - Zygomatic leiomyoma. Case report.
AB  - Leiomyoma is a benign tumor that originates from the smooth muscle. If often
      develops in the uterus and in organs rich of smooth muscle like bowel and
      subcutaneous tissue. It is infrequently observed in the oral nasal cavities or in
      paranasal sinuses. The authors, after an accurate revision of the literature,
      present their first case of zygomatic leiomyoma. They underline the diagnostic
      aspects in relationship to histologic and immunohistochemical examinations, for
      surgical therapy.

PMID- 9002712
TI  - Arteriovenous malformations of the corpus callosum--radioanatomic study and
      effectiveness of intranidus embolization.
AB  - Forty-three patients with arteriovenous malformations (AVMs) of the corpus
      callosum treated by embolization were reviewed. The following clinical and
      radioanatomic characteristics were found: 84% (36 patients) presented with
      intracranial hemorrhage, 43% (20 nidi) of the lesions were located in the
      posterior half of the corpus callosum, multiple nidi were more frequent (21%)
      than expected, 27 nidi (59%) were fed by branches of both the anterior and
      posterior cerebral arteries, AVMs mainly drained into the internal cerebral vein
      and/or interhemispheric superficial veins, and 19 (41%) had both draining
      pathways, 10 patients (23%) had impaired drainage through the straight sinus due
      to dysplasia. Staged embolization was performed in 245 feeders. Curative
      occlusion (more than 95%) was obtained in 17 patients (40%) and considerable
      occlusion (more than 75%) in 33 patients (77%). Large and giant, diffuse-type,
      and multifocal AVMs were difficult to completely embolize. Complications
      associated with embolization occurred in six patients, mostly during the first 5
      years. Only two patients had a permanent deficit related to a complication.
      Overall morbidity and mortality were 7% and 2%, respectively. Nine patients were
      referred for stereotactic radiosurgery, three of whom were completely cured and
      five patients have not been assessed. Most AVMs in the corpus callosum are
      supplied by multi-axial feeders, so multi-target intranidus embolization is very
      important to prevent the development of other feeders secondary to the
      hemodynamic shift. Combined therapy using maximum embolization and subsequent
      radiosurgery may be the most effective method to treat AVMs in the corpus
      callosum.

PMID- 9002713
TI  - Intracranial aneurysms associated with moyamoya disease.
AB  - The authors examined 31 patients with moyamoya disease in Yugoslavia. Among them
      four intracranial aneurysms were disclosed, two in males and two others in
      females. The aneurysms, which were present in adult patients only, were diagnosed
      angiographically. Three of four patients died several days or weeks after onset
      of hemorrhage. The aneurysms were located within the basal abnormal vascular
      network, on a distal branch of the posterior cerebral artery, on the top of the
      basilar artery, and on the posterior branch of the middle meningeal artery. The
      moyamoya disease on the side of the individual aneurysms was most often stage III
      or IV.

PMID- 9002714
TI  - Elevated plasma basic fibroblast growth factor in brain tumor patients.
AB  - We attempted to determine whether the plasma concentration of basic fibroblast
      growth factor (bFGF) was elevated in brain tumor patients. The plasma
      concentration of bFGF was measured in 55 brain tumor patients and 17 normal
      subjects by enzyme immunoassay. Upper limit of plasma bFGF in the normal subjects
      was 1.6 pg/ml. Elevated plasma bFGF levels were observed in 28 patients including
      13 of 17 glioma patients, eight of 19 benign tumor patients, and seven of 19
      malignant tumor patients. Twelve of 14 malignant glioma patients had elevated
      plasma bFGF levels. There was a good correlation (r = 0.42, p < 0.05) between the
      elevated plasma bFGF level and the tumor volume. Further studies are needed to
      determine whether the plasma bFGF level is a clinically useful diagnostic and
      prognostic marker for patients with brain tumors.

PMID- 9002715
TI  - Long-term evaluation of radiation-induced brain damage by serial magnetic
      resonance imaging.
AB  - The long-term changes during late delayed radiation-induced brain damage were
      investigated by serial magnetic resonance (MR) imaging of eight patients over a
      mean follow-up period of 45 months after irradiation. The radiation damage
      appeared as an enhanced lesion on T1-weighted MR images with gadolinium
      diethylenetriaminepenta-acetic acid (Gd-DTPA) at 3 to 30 months after
      radiotherapy (mean 12.8 months). In all patients, an abnormal high signal
      intensity area on T2-weighted imaging preceded the enhanced lesion. The volume
      and number of enhanced lesions continued to increase for 3 to 23 months (mean
      10.3 months). The high signal intensity area on T2-weighted imaging
      simultaneously expanded. The lesions were subsequently stabilized, and in four
      long-term survivors, the Gd-DTPA-enhanced lesions then decreased in size, the
      intervals from onset to regression were 12, 13, 17, and 35 months (mean 19.3
      months), respectively. However, two patients showed a relapse of the enhanced
      lesion with latent periods of 8 and 9 months, respectively. Finally, the
      radiation-damaged brain became atrophic including the high signal intensity area
      on T2-weighted images. Late delayed radiation-induced brain damage continues to
      progress for over a year and then regresses, but thereafter a relapse may occur.

PMID- 9002716
TI  - Cerebrospinal fluid rhinorrhea secondary to small tumor invasion into the
      superior sagittal sinus--case report.
AB  - A 53-year-old male presented with non-traumatic cerebrospinal fluid rhinorrhea
      due to obstructive extension of a small parasagittal meningioma. Radical excision
      of the tumor was curative. The rhinorrhea apparently developed due to increased
      intracranial pressure associated with primary empty sella.

PMID- 9002718
TI  - Hemifacial spasm due to compression of the facial nerve by vertebral artery
      posterior inferior cerebellar artery aneurysm and elongated vertebral artery-
      case report.
AB  - A 62-year-old female presented with rapid aggravation of long-standing facial
      spasm occurring within a few months. Neuroimaging and angiography demonstrated
      compression of the root exit zone (REZ) of the facial nerve by an ipsilateral
      saccular aneurysm at the left vertebral artery (VA)-posterior inferior cerebellar
      artery bifurcation, in addition to the elongated VA. Neck clipping of the
      aneurysm and decompression of the REZ from the elongated VA and clipped aneurysm
      resulted in complete disappearance of the facial spasm. The aneurysm had very
      thin walls and was apparently about to rupture. Aggravation of long-standing
      hemifacial spasm may be a warning sign for rapid growth and rupture of a
      causative aneurysm.

PMID- 9002717
TI  - Brainstem schwannoma--case report.
AB  - A 68-year-old female presented with rare brainstem schwannoma manifesting as
      right hemiparesis, diplopia, and dysphagia. Neuroimaging revealed a lesion in the
      pons and cerebral peduncle, which was supposed to be a highly malignant glioma.
      The mass was approached via a single-flap orbitozygomatic craniotomy through an
      anteromedial pericavernous approach. Intraoperative frozen-section specimens
      indicated glioma, but the tumor was distinct from the surrounding parenchyma, and
      could be removed successfully. A tumor capsule was found and also removed.
      Postoperative histological, immunohistochemical, and ultrastructural examinations
      confirmed the diagnosis of benign schwannoma. Most schwannomas, even in the
      brainstem, are benign and complete removal may be curative.

PMID- 9002719
TI  - Intramedullary spinal cord meningioma--a case report.
AB  - A 54-year-old female presented with a spinal intramedullary meningioma
      manifesting as extremely slow development of dysesthesia in the extremities.
      Sagittal T1-weighted resonance imaging showed fusiform enlargement of the
      cervical spinal cord with an area of low-signal intensity suggestive of
      syringomyelia extending bidirectionally up to the medulla oblongata and downward
      from the homogeneously enhanced intramedullary space-occupying lesion. The tumor
      was confirmed to be intramedullary mass with no dural attachment, and was totally
      removed en bloc. Histological examination showed transitional type of meningioma.
      The tumor specimen was positive for epithelial membrane antigen, and included
      glial fibrillary acidic protein-positive fibers, which were thought to be
      surrounding neural tissues trapped by the nodularity of the tumor in the growing
      process.

PMID- 9002720
TI  - Vein of Galen aneurysmal malformation in a neonate treated by endovascular
      surgery--case report.
AB  - A male neonate with vein of Galen aneurysmal malformation developed fetal heart
      failure after a gestation period of 37 weeks. Labor was induced, but a cesarean
      section had to be performed because of fetal distress. His Apgar scores were 2/8
      at birth. The boy required controlled ventilation due to generalized seizure and
      cyanosis. Neuroimaging revealed vein of Galen aneurysmal malformation with
      enormous arteriovenous shunt flows. Transarterial embolization was performed on
      days 4 and 6 to reduce the progressive high-output congestive heart failure.
      Three large feeders were occluded with interlocking detachable coils, markedly
      reducing the shunt flow. Although heart failure improved markedly, he died of
      pulmonary hemorrhage on day 12. Endovascular surgery can improve the prognosis of
      heart failure in the neonatal period less invasively than other treatment
      modalities, and may help to minimize ischemic brain damage and thus increase the
      possibility of normal brain maturation.

PMID- 9002722
TI  - New Year's resolutions for Washington.

PMID- 9002721
TI  - Arachnoid-trabeculae tenting as a self-retaining retractor in resecting ventrally
      located spinal meningioma--technical note.
AB  - Tenting of the arachnoid with intact trabeculae to facilitate and maintain
      rotation of the cord during the resection of ventrally or ventrolaterally located
      spinal meningiomas is proposed. The arachnoid-trabeculae tenting acts as a self
      retaining retractor, and prevents overlapping of the cord onto the tumor due to
      gravity.

PMID- 9002723
TI  - Interview with Karen Hasby. Interview by Bill Berlin.

PMID- 9002724
TI  - The debate over cardiac catheterization.
AB  - At first glance, there would seem to be little controversy over cardiac
      catheterization, a diagnostic procedure used to evaluate problems with heart
      function and blood supply. In a typical cardiac catheterization, a long thin tube
      is inserted through blood vessels into the heart to evaluate blood pressure,
      inject dye, and take x-rays.

PMID- 9002725
TI  - Drug-resistant Streptococcus pneumoniae in New Jersey.

PMID- 9002726
TI  - Physician assistants come of age in New Jersey.
AB  - Until recently, New Jerseyans' exposure to physician assistants (PAs) was through
      television programs such as "E.R." But with the 1992 legislation enabling PAs to
      work in New Jersey and a growing acceptance among physicians, patients are seeing
      more of these health care providers in the examining room.

PMID- 9002727
TI  - Assisted living and alternative family care options.

PMID- 9002728
TI  - How can we provide subacute care?

PMID- 9002729
TI  - Reflections from 1996 and a look at 1997.

PMID- 9002730
TI  - Pre-trial phase of dental malpractice case: the summons and complaint.
AB  - Dental malpractice litigation in not that easy to commence. It is filled with
      procedural obstacles and rules that must be met by a plaintiff. Sometimes this
      can seem bewildering to a dentist, and while it is supposed to be designed to
      weed out frivolous lawsuits, it often causes more stress for the dentist rather
      than less.

PMID- 9002731
TI  - Heading in the wrong direction.

PMID- 9002732
TI  - Times change.

PMID- 9002733
TI  - Alternative protocol.

PMID- 9002734
TI  - Getting the word out on dental benefits.

PMID- 9002735
TI  - A survey of faculty practices in U.S. dental schools.
AB  - In addition to providing a mechanism for maintenance and enhancement of the
      clinical skills of the faculty, intramural faculty practices are seen as an
      increasingly important source of revenue for dental schools. In this paper, we
      report on a survey conducted during academic year 1993/94 of United States dental
      schools as to the existence, organization, physical structure, finances and
      governance of their faculty practices. Results showed that all dental schools
      surveyed had some form of faculty practice or plan to establish a faculty
      practice in the future. The mean gross income of schools with established faculty
      practices in the 1993/94 academic year was 1.55 million dollars. Almost all sub
      disciplines were represented in these faculty practices. More than 90 percent of
      the practices are housed within the dental school. The major cost to the faculty
      practice was staff salaries, with approximately 40 percent of the gross going to
      faculty reimbursement. Although 60 percent of the faculty practices surveyed were
      under the direct control of the dental school administration, a significant
      number of faculty practices were either corporations or partnerships. The results
      of the survey indicate a continuing trend towards the establishment of dental
      school-based intramural practices as a means of supporting the dental school
      budget.

PMID- 9002736
TI  - Halitosis. A common oral problem.
AB  - Halitosis is caused primarily by bacterial putrefaction and the generation of
      volatile sulfur compounds. Ninety percent of patients suffering from halitosis
      have oral causes, such as poor oral hygiene, periodontal disease, tongue coat,
      food impaction, unclean dentures, faulty restorations, oral carcinomas, and
      throat infections. The remaining 10 percent of halitosis sufferers have systemic
      causes that include renal or hepatic failure, carcinomas, diabetes or
      trimethylaminuria. Modern analytical and microbiological techniques permit
      diagnosis of bad breath. Management of halitosis involves maintaining proper oral
      hygiene, and periodontal treatment, including tongue brushing.

PMID- 9002737
TI  - Nursing home dentistry.
AB  - A recent review of international literature on dentistry in geriatric nursing
      homes reveals an epidemic of undertreated caries, periodontal disease and
      edentulousness. Obstacles to a remedy are the complex medical condition of the
      elderly, confusion over protocol and inadequate funding.

PMID- 9002738
TI  - Guided tissue regeneration in dentistry.
AB  - Guided tissue regeneration (GTR) is a technique currently used in dentistry for
      periodontal surgery, oral surgery, implant dentistry and reconstruction of
      maxillomandibular defects. The basic premise for this technique is to allow for
      osseous regeneration prior to soft tissue migration into the area of interest.
      This is accomplished with the use of membranes that prevent the migration of the
      soft tissue element into the bony defect. This paper discusses current uses for
      GTR techniques and reviews some of the materials now available for this purpose.

PMID- 9002739
TI  - Ten years of experience with MIBG applications and the potential of new
      radiolabeled peptides. Proceedings of an international workshop. Rome, Italy,
      June 3, 1994.

PMID- 9002740
TI  - The current status of meta-iodobenzylguanidine and related agents for the
      diagnosis of neuro-endocrine tumors.
AB  - Metaiodobenzylguanidine (MIBG) has been in clinical use for 15 years and has been
      shown to have high sensitivity (about 85%) and specificity (> 95%) for the
      location of all types of pheochromocytomas. Similar results have been achieved
      with neuroblastomas. A wide range of other neuroendocrine lesions including
      carcinoids, medullary thyroid cancer and nonsecretory paragangliomas may also be
      imaged, but the lower sensitivity. The newly developed radiolabeled somatostatin
      analogs may have greater utility for these lesions. MIBG scintigraphy may also
      provide a unique in vivo probe for study of the sympathetic autonomic nervous
      system, particularly in the heart. Various radiolabels for MIBG and its analogs
      permit planar scintigraphy, SPECT, PET, intraoperative probe localization and
      radiopharmaceutical therapy.

PMID- 9002741
TI  - Meta-[123I]iodobenzylguanidine single photon emission computed tomography in
      chemodectomas.
AB  - Chemodectoma is a rare, slow growing neoplasm with local aggressiveness and a
      high rate of residuals after surgery, arising from paraganglionic tissue (neural
      crest) and therefore able to take up Metaiodobenzylguanidine (MIBG). The aim of
      this study was to evaluate the diagnostic accuracy of 123I-MIBG Single Photon
      Emission Computed Tomography (SPECT) in comparison to Selective Digital
      Angiography (SDA), Computed Tomography (CT) and Magnetic Resonance Imaging (MRI).
      We studied 50 patients (41 women, 9 men) mean age 56 years (range 14-79), with
      diagnostic suspicion of chemodectoma (CH). There were 2 groups of patients: Group
      A (26 patients) examined before Surgery and Group B (24 patients) examined after
      surgery. SPECT of the head and neck region was performed 4 hours after i.v.
      administration of 185 MBq of 123I-MIBG. All patients were pre-treated with iodine
      solution. We performed a qualitative evaluation of the reconstructed slices. In
      Group A, all patients with CH (24) showed accumulation of MIBG in agreement with
      SDA, CT and MRI: 2 patients (histologically one had a cordoma, the other
      metastasis of papillary thyroid carcinoma), did not show any accumulation of 123I
      MIBG. In Group B, 6 patients showed accumulation of 123I-MIBG in local residuals,
      and 9 were negative. Six patients with a lesion smaller than 1.5 cm were
      negative. Three patients had a positive scan but no lesion on SDA, CT and MRI.
      123I-MIBG SPECT proved to be useful procedure in the diagnosis of untreated CH.
      During follow-up after surgery this procedure may assume a role in the
      perspective of radiometabolic therapy with 131I-MIBG.

PMID- 9002742
TI  - Meta-[131I]iodobenzylguanidine in the scintigraphic evaluation of neural crest
      tumors.
AB  - Since February 1990, 74 patients (116 studies) underwent scintigraphy with meta
      [131I]iodobenzylguanidine ([131I]MIBG). Eighteen patients had pheochromocytomas,
      2 paragangliomas, 2 malignant insulinomas, 1 carcinoid, 2 medullary thyroid
      carcinoma and 49 children had neuroblastomas. Scintigraphy was performed
      following a thyroid blockade, at 24 and 48 hours after i.v. injection of 0.5
      mCi/1.7 m2 [131I]MIBG. Grade of heart intensity (GHI) uptake and the intensity of
      salivary gland visualization (SGI) were estimated semiquantitatively, according
      to the method of Nakajo et al. Sensitivity in the primary pheochromocytomas was
      93.9%; sensitivity and specificity in the primary neuroblastomas were 93.7% and
      100% respectively; in the secondary neuroblastomas they were 100%, and 100%.
      Metastases in 2 malignant insulinomas and in 1 case of medullary thyroid
      carcinoma were also demonstrated. Only one false negative (in pheochromocytoma)
      and one false positive (Conn's syndrome) result was obtained. Mean values and
      range of MIBG uptake measured according to Shulkin's procedure were: for
      pheochromocytoma 3.95% (0.1-15), primary neuroblastoma 0.7% (0.05-1.92%), and
      neuroblastoma metastases 0.12% (0.002-0.83%). Assessment of [131I]MIBG uptake
      seems to be helpful in the follow-up of some neural crest tumors and is essential
      as a prelude to [131I]MIBG therapy.

PMID- 9002743
TI  - Upper clavicular and cardiac meta-[123I]iodobenzylguanidine uptake in children.
AB  - In order to clarify some of the particularities and pitfalls of the MIBG thoracic
      scan, we report our experience with 5 children with Stage III or IV neuroblastoma
      who presented equivocal scans. The physiological thoracic distribution of MIBG in
      children differs from that in adults and has to be taken in account in the
      accurate interpretation of the scans.

PMID- 9002744
TI  - Radioiodinated meta-iodobenzylguanidine in the diagnosis of childhood
      neuroblastoma.
AB  - In a group of 97 patients aged from 6 months to 12 years, all with suspected or
      proven neural crest tumours, metaiodobenzylguanidine (MIBG) scintigraphy was
      performed at the time of diagnosis and, in some instances, after induction
      chemotherapy. All the patients underwent a tumour biopsy with cytological and
      histological analysis, in addition to imaging examinations such as X-rays,
      ultrasound, computed tomography and magnetic resonance, within a short period
      before or after scintigraphy. In 82 of 97 cases MIBG was effective in detecting
      the primary tumour, hence the technique's sensitivity was 84%. A significant
      different of sensitivity between [131I]MIBG and [123I]MIBG was not demonstrated.
      As regards metastatic locations, MIBG scans revealed one or more bone metastases
      in 12 cases, bone marrow involvement (assumed to be present when diffuse and
      symmetric uptake in the spine, pelvis and possibly other skeletal sites were
      visualized) in 9 cases, and focal liver metastases or hepatomegaly in 4 cases.
      Probably owing to the restrictive diagnostic criterion adopted or to the early
      phase of the bone marrow involvement, the last was found by biopsy but missed by
      MIBG in 25 cases. The overall sensitivity in detecting metastases was low (48%),
      but it was much higher if only bone metastases were considered (81%). Twenty-nine
      patients who had positive scans at diagnosis were checked following 1-2 courses
      of induction chemotherapy (IC). MIBG scans remained positive in 22 primary
      tumours, while 7 primary masses were no longer detected. Out of 12 cases showing
      metastases at diagnosis, two cases with liver lesions became normal and in one
      case some, but not all, of the bone lesions were not detectable; 4 cases remained
      abnormal, while in 5 cases bone marrow involvement was not confirmed. Three cases
      were confirmed to be true negatives; in 4 other cases bone marrow involved not
      showing at diagnosis was revealed and confirmed by biopsy; 3 cases in which bone
      marrow involvement was not revealed by MIBG at diagnosis, had normal MIBG and
      biopsy results after IC; finally, 2 false negative bone marrow cases and 5 true
      negative cases at diagnosis remained unchanged, but were not checked by biopsy.
      Performing total body MIBG scintigraphy in childhood neuroblastoma at diagnosis
      is useful: 1) to predict the nature of the masses detected by other imaging
      techniques, when biopsy has not yet been performed; 2) for more accurate tumour
      staging, in addition to standard imaging investigations, MDP scintigraphy and
      bone marrow aspiration biopsy, thanks to its ability to detect metastatic
      lesions; 3) to anticipate the decrease in sensitivity of the technique in
      detecting both the primary mass and the metastases following induction
      chemotherapy.

PMID- 9002745
TI  - [123I]MIBG scintigraphy in neuroblastoma: a comparison between planar and SPECT
      imaging.
AB  - The aim of the present study was to assess the utility of SPECT imaging with
      [123I]MIBG in patients with neuroblastoma (NB). Twenty-two children were studied
      (11 males and 11 females: age range: newborn to 11 years). A total of 39 studies
      were performed in different clinical phases. Both planar (at 24 and occasionally
      48 hours) and SPECT (at 24 hours) imaging were performed in all cases. Planar
      studies gave a sensitivity of 87.5% (evidence of the disease in 21 of 24 studies
      performed in children with known NB lesions) and a specificity of 93.3% (true
      negative results in 14 of 15 studies performed in disease-free patients). In the
      same patients SPECT gave a sensitivity of 95.8% (23 of 24 positive studies and a
      specificity equal to that of planar scanning. In 5 of 21 studies positive at
      planar scanning SPECT showed 9 additional lesions. In conclusion, [123I]MIBG
      SPECT imaging compared to planar scanning can demonstrate a greater number of
      lesions. Its use seems to be indicated mainly in cases in which diagnostic
      assessment is difficult, such as small residual tumors or in the follow up of
      children no longer in therapy, in whom it can lead to an early diagnosis of
      relapse.

PMID- 9002746
TI  - Clinical use of metaiodobenzylguanidine imaging in cardiology.
AB  - Cardiac function is predominantly regulated by autonomic innervation. Many heart
      diseases involve alterations of cardiac adrenergic neurotransmission. In patients
      with cardiomyopathies, numerous therapeutic agents act directly or indirectly on
      cardiac adrenergic disorders. Metaiodobenzylguanidine (MIBG) imaging can provide
      in vivo information on one of the main components of adrenergic nerve function,
      i.e. the norepinephrine reuptake and storage system. Diminished MIBG uptake has
      been reported in patients with congestive heart failure, indicating an impaired
      norepinephrine reuptake and storage system. In patients with dilated
      cardiomyopathy (either idiopathic or ischemic), this alteration has been linked
      to the severity of the disease, evaluated on the basis of clinical or hemodynamic
      parameters. Moreover, MIBG imaging has been reported in such patients to be a
      potent prognostic marker in comparison with other recognized indices. After
      myocardial infarction, the decrease in MIBG uptake was transient in some patients
      and was suggested to be a viability indicator. Diminished MIBG uptake in ischemic
      patients was linked to the occurrence of ventricular arrhythmias. In patients
      with primary hypertrophic cardiomyopathy, decreased cardiac MIBG uptake has also
      been related to the clinical indices of severity. In patients suffering from
      various arrhythmias such as idiopathic ventricular arrhythmias, arrhythmogenic
      right ventricular cardiomyopathy or a long-QT syndrome, MIBG imaging has
      evidenced regional abnormalities of adrenergic nerve function and has provided
      new insights into the pathophysiological mechanisms of such disorders. Finally,
      MIBG scintigraphy may permit the evaluation of anthracyclin cardiotoxicity. Thus,
      MIBG imaging appears to be a promising tool for the cardiologist.

PMID- 9002747
TI  - Regional sympathetic denervation after myocardial infarction: a follow-up study
      using [123I]MIBG.
AB  - Previous studies in dogs have shown that experimental infarction produces
      myocardial sympathetic denervation not only in the infarcted area, but also in a
      region apical to the infarction. In these dogs MIBG myocardial scintigraphy
      detected denervation but returned to normal in a few months at which time
      reinnervation was shown to have occurred. Myocardial sympathetic denervation was
      studied with MIBG scintigraphy in ten patients after their first acute transmural
      myocardial infarction; scans were repeated at 4 months, one year and 30 months to
      follow the time course of possible reinnervation. Except during the first 48
      hours following the infarction, no therapy except for antiaggregants was
      administered to the patients; during this follow-up period no cardiac events were
      seen. One week after infarction, comparison of MIBG images with perfusion scans
      revealed that the denervated area was larger than the infarcted area; no
      difference in MIBG uptake by the infarcted myocardium was found during the 30
      months follow-up.

PMID- 9002748
TI  - Use of [123I]MIBG to assess cardiac adrenergic innervation: experience in
      hypertensive cardiopathy and left ventricular aneurysms.
AB  - [123I]MIBG has been proposed as a suitable tracer of the adrenergic system of the
      heart. The aims of this study was to investigate the adrenergic functional status
      of the heart in hypertensive patients with left ventricular hypertrophy (LVH),
      and to evaluate the distribution of neuroadrenergic terminals in patients with
      left ventricular aneurysms (LVA) presenting complex arrhythmias. We studied 21
      patients (4 normals, 11 with LVH and hypertension, and 6 with previous myocardial
      infarction, LVA and complex arrhythmias) who underwent series of [123I]MIBG
      planar scans (from 0.5 to 24 hours p.i.) and SPECT scans using both [123I]MIBG
      and 201Tl. Data quantification was performed by calculating the heart/mediastinum
      ratio (planar scan) and the percent uptake in 5 myocardial regions (SPECT scan).
      No significant differences between normals and hypertensive patients were found
      either in the heart/mediastinum ratio or in the regional distribution of
      [123I]MIBG and 201Tl. In hypertensive patients the uptake of [123I]MIBG was
      significantly higher than that of 201Tl in the septal wall while in the lateral
      and inferior walls it was significantly lower. In patients with anteroapical
      myocardial infarction (MI), the size of the [123I]MIBG defect was slightly
      smaller than the 201Tl defect; moreover a constant, severe [123I]MIBG defect was
      observed in the inferior walls whereas 201Tl uptake was normal. We conclude that
      while in hypertensive patients adrenergic innervation seems to be slightly
      impaired as compared to myocardial perfusion, in patients with MI a large area of
      functional or anatomical denervation may be detected despite the preserved
      perfusion and viability; this mismatch may be the trigger of complex arrhythmias.

PMID- 9002749
TI  - Use of metaiodobenzylguanidine (MIBG) in pneumology.
AB  - Norepinephrine (NE) is one of the many biologically active substances that are
      metabolized by the lung. The norepinephrine uptake in the lung has been widely
      investigated in animal studies in order to detect abnormalities of the
      endothelial cells. 131I- or 123I-labelled metaiodobenzylguanidine (MIBG) is a
      radioactive tracer that shares several metabolic pathways with NE; it has been
      used instead NE or both in animal and in human studies for the same purposes. It
      has been definitely demonstrated that MIBG lung uptake following intravenous
      administration is a reliable marker of minimal endothelial cell lesions and it
      allows one to investigate several conditions involving damage to the lung
      vasculature such as adult respiratory distress syndrome, post-actinic lung
      fibrosis or chemotherapic lung toxicity. MIBG could also potentially be used as a
      tracer of the neuroadrenergic system of the airways, once it has been deposited
      in the whole branches of the bronchial tree. With this in mind we evaluated the
      feasibility of the administration of MIBG in radioaerosol form. We first
      performed a chromatographic study on [123I]MIBG aliquots aerosolized for variable
      lengths of time (2-30 minutes). Radiochemical purity was always over 96%, thus
      demonstrating that aerosolization does not significantly modify the stability of
      the tracer. We then compared both the lung clearance curves and the scintigraphic
      images in two groups of normal subjects who respectively underwent [123I]MIBG and
      99mTc-DTPA radioaerosol dynamic scintigraphy. We found that MIBG clearance to be
      significantly lower than that of DTPA (135 +/- 32 minutes versus 69 +/- 27
      minutes, p < 0.01), probably due to its being trapped in the adrenergic nerve
      endings of the airways. The pulmonary distribution of both tracers was
      homogeneous, as demonstrated by the correspondence of the values for the aerosol
      penetration index in both groups of subjects. Such results warrant further
      research and pharmacologic tests.

PMID- 9002750
TI  - The current status of radioiodinated metaiodobenzylguanidine therapy of neuro
      endocrine tumors.
AB  - The avidity of many metastatic pheochromocytomas and neuroblastomas for
      metaiodobenzylguanidine (MIBG) observed at diagnostic scintigraphy has led to
      attempts to treat these lesions with large doses of MIBG. We and others have
      achieved therapeutic responses with 131I-MIBG (usually partial) in about a third
      of malignant pheochromocytomas. A small but important subgroup of advanced, poor
      prognosis neuroblastomas which have been resistant to all other therapies have
      also shown responses including occasional long-term survival (> 5 years) and
      apparent complete responses to 131I-MIBG. Because the physical properties of 131I
      are suboptimal for the delivery of therapeutic radiation to bone marrow
      micrometastases, a frequent problem in neuroblastoma, we have performed
      preliminary studies in poor prognosis Stage III and VI neuroblastoma using 125I
      MIBG which has more satisfactory emissions. This has led to prolonged tumor
      stabilization and survival (> 19 to > 52 months) in 5 of 10 patients. MIBG
      radiopharmaceutical treatment of neuroendocrine tumor patients must still be
      considered an experimental but nevertheless promising treatment modality.

PMID- 9002752
TI  - [131I]MIBG as a first line treatment in advanced neuroblastoma.
AB  - The observed response to [131I]MIBG therapy in advanced neuroblastoma after
      conventional therapy, the noninvasiveness of the procedure, and the high
      metabolic activity which is frequently observed in untreated tumors led to the
      concept of substituting [131I]MIBG therapy for combination chemotherapy at
      diagnosis prior to surgery in patients with advanced disease/high risk
      neuroblastoma. The objective of this approach is to reduce the tumor volume,
      enabling adequate surgical resection of the tumor, and to avoid toxicity and the
      induction of early drug resistance. Chemotherapy is reserved to treat minimal
      residual disease postoperatively. Thirty-one children who presented with
      inoperable neuroblastoma were treated according to this protocol. After an
      objective response to [131I]MIBG therapy at diagnosis, 19 of 27 evaluable
      patients (70%) had complete or > 95% resection of the primary tumor or did not
      require surgery at all. Only mild hematological toxicity was observed. It is
      concluded that [131I]MIBG therapy of neuroblastoma at diagnosis is feasible; its
      effectiveness in attaining operability of the primary tumor is at least equal to
      that of combination chemotherapy, but its toxicity is considerably less.

PMID- 9002751
TI  - Place of meta-[131I]iodobenzylguanidine in the treatment of neuroblastoma: the
      Genoa experience.
AB  - The aim of this paper is to focus on our previous experience with the treatment
      of Group 3 and 4 neuroblastoma patients and on the therapeutic use of [131I]MIBG,
      to better define the role of this radioactive drug in the treatment of
      neuroblastoma (NB). Analysis of the studies on Group 3 patients treated with
      chemotherapy and surgery showed that the progression-free survival (PFS)
      increased from 45% for patients treated before 1985 to 63% for patients treated
      in the period of 1985-1989 and to 78% for patients treated after 1989. [131I]MIBG
      administered in 17 Group 3 patients who did not achieve a radical excision of the
      primary resulted in 7 partial response (PR) and 5 minor response (MR), with 10
      cases of long term survival. Results in Group 4 patients confirmed the good
      prognosis in the subset of children aged 6-12 months at diagnosis (PFS 86% at 5
      years). In patients aged > 12 months at diagnosis intensive induction
      chemotherapy induced a higher response rate of 69% and PFS was 26% at 5 years.
      [131I]MIBG administered in advanced stage 4 patients induced a response in 50% of
      the cases (2 complete response [CR], 13 PR and 2 MR out of 34 children) and 8
      children treated for residual primary (4 cases) or residual bone metastases (4
      cases) are long term survivors. We conclude that [131I]MIBG is the treatment of
      choice in Group 3 patient with a residual primary tumor and could contribute to
      consolidate the response obtained in Group 4 patients.

PMID- 9002753
TI  - The treatment of neuroblastoma with [131I]MIBG at diagnosis.
AB  - The potential role [131I]MIBG therapy in untreated, inoperable cases of
      neuroblastoma (NB) in children was evaluated. Six children, aged 10 months-5
      years, were treated at diagnosis. Five (4 stage III and 1 stage IV NB) underwent
      [131I]MIBG treatment alone (single doses ranging from 2.9 to 6.1 GBq of high
      specific activity [131I]MIBG. In one case (stage IV NB) [131I]MIBG was preceded
      by Cisplatin administration (20 mg/m2/day) given over a 5 day period. The results
      obtained in the first 5 cases were as follows: 1 complete response still lasting
      after 5 years; 1 partial and 1 minor response allowing further surgery and
      chemotherapy; 2 stabilization of the disease. The treatment was well tolerated
      with minimal toxicity. However, apart from the first case all these children
      relapsed and subsequently died. Therefore [131I]MIBG therapy (9.1 GBq given in 2
      courses) combined with Cisplatin as a "radiosensitizer" was used in the sixth
      case, a patient with widespread bone metastases and massive bone marrow
      involvement. A very good partial response was obtained in this case. Further
      surgery (of the primary NB) and multidrug chemotherapy was then possible. In
      conclusion, [131I]MIBG therapy at diagnosis appears to be effective, low toxic
      treatment of NB; when integrated with Cisplatin its efficacy seems to improve
      even more.

PMID- 9002754
TI  - Treatment with meta-[131I]iodobenzylguanidine and cisplatin in stage IV
      neuroblastoma.
AB  - Metastatic neuroblastoma (NB) continues to have a dismal prognosis. NB is a
      radiosensitive tumor. Owing to its high concentration in the NB lesions,
      Metaiodobenzylguanidine (MIBG) has the potential for specifically delivering very
      large radiation doses to the malignant cells. Encouraging results have been
      reported with [131I]MIBG used alone in patients resistant to conventional therapy
      and at diagnosis. We report the first attempts to explore the integration of this
      new treatment modality with chemotherapy. Among the drugs effective in NB,
      cisplatin was chosen because of its high degree of activity against NB, its mild
      hematologic toxicity and the known synergism between cisplatin and radiation.
      Four patients, 3 with relapsed, heavily pre-treated, progressive stage IV NB, and
      1 with stage IV NB at diagnosis, all with a good [131I]MIBG uptake, were
      investigated with the combined therapy. Two complete remissions and one partial
      remission were observed in the relapsed patients 4-6 weeks following only one
      single course of both cisplatin and [131I]MIBG at the "standard" dosage. The only
      toxicity was hematologic, which was significant and relatively long-lasting, but
      was not associated with any serious infections or bleeding tendency. The general
      condition of these patients during the entire study period was excellent. The 4th
      patient, investigated at diagnosis with a modified less intensive treatment,
      obtained a partial remission with a mild hematologic toxicity. The provisional
      conclusion of this preliminary study is that this new form of combined therapy
      appears very effective in heavily pretreated relapsed patients with progressive
      disease, and could also be investigated in refractory patients and in patients at
      diagnosis.

PMID- 9002757
TI  - Receptor ligands.

PMID- 9002756
TI  - Membrane receptors and hormones.
AB  - The regulation of metabolic processes, cell growth and differentiation is
      achieved by an interaction between hormones and specific cellular binding sites
      termed "receptors". These may be located on the cellular surface, in the
      cytoplasm or in the nucleus. Recently the structure of several membrane receptors
      in mammalian cells have been elucidated. These consist of peptide chains
      possessing multiple functional "domains". We describe in details the
      extracellular, transmembrane and intracellular "domains". In recent years
      antibodies to many receptors and analogues of some peptide hormones have become
      available; these can be used in clinical practice to study receptors, their
      localization and, in some cases, to block their function.

PMID- 9002755
TI  - In vitro and in vivo studies with no-carrier added radioiodinated MIBG.
AB  - An important drawback of radioiodinated MIBG prepared by isotopic exchange
      (maximum specific activity: 100 Ci/mmol) is that a considerable amount of carrier
      is present in the "ready to use" radiopharmaceutical, thus affecting MIBG uptake
      in the target cells. To improve the therapeutic utility of MIBG an interesting
      method was developed for the no-carrier-added (n.c.a.) radioiodination of MIBG
      via a halodesilylation reaction using 3-trimethylsilybenzylguanidine (TMSBG) as
      precursor. In order to investigate its possible clinical usefulness, n.c.a.
      [125I]- and [131I]MIBG was prepared according this procedure. HPLC analysis of
      the labeling mixture showed that the labeling yield reached values greater than
      98% within 20 minutes at 70 degrees C. HPLC fraction containing [131I]MIBG was
      then recovered and tetrahydrofurane was removed under nitrogen stream.
      Biodistribution studies were performed in BALB/c normal mice and compared with
      those obtained using [131I]MIBG prepared by isotopic exchange. Preliminary
      results showed that at 4 hours myocardial uptake was significantly higher than
      that of c.a. MIBG (20.3 +/- 0.4 %ID/g). Adrenal uptake gradually increased over
      time; at 24 hours adrenal uptake was almost twofold that a 1 hour. MIBG uptake
      was also studied in the human neuroblastoma cell line SH-SY5Y which has a
      specific uptake system for MIBG. The kinetic parameters for MIBG in this line
      are: km = 0.27 +/- 0.03 microM, Vmax = 39.5 + 1.8 pmol/10(6) cell/10 min.
      Preliminary data from in vitro binding studies showed that significantly higher
      levels of specifically incorporated radioactivity can be achieved using n.c.a.
      [125I]MIBG instead of c.a. [125I]MIBG.

PMID- 9002758
TI  - Description of a multicompartmental model of the biodistribution of 111In-DTPA-D
      Phe-1-octreotide in human.
AB  - The aim of this study was to use compartmental analysis as a theoretical tool to
      provide quantitative and unitary data for a more precise determination of 111In
      OCT concentrations in a tumour site and various body organs. Five subjects (3
      male and 2 female) with neoplasias were studied. Structural and parametric
      identification of the model was based on the plasma, urine, total body and ROI
      (soft tissue, spleen, kidney and tumour) activity values. The model was of the
      mammillary type with 5 compartments (blood, soft tissue, spleen, kidneys and
      urine) for the 4 patients with a negative scintiscan and 6 (blood, soft tissue,
      spleen, kidneys, urine and tumour) for the adenocarcinoma patient. Numerical
      constants were determined by running a best-fit procedure with the MINUIT
      minimisation program (CERN library) using a microVAX 3800 computer. The
      reliability of the models was also tested. 111In-OCT accumulates in the kidneys
      and spleen, from which it is slowly released into the blood. Elimination is via
      the urine at first rapidly, then more slowly. The maximum concentration in the
      tumour compartment is reached at 12-14 hours and remains almost constant.

PMID- 9002759
TI  - [111In-DTPA-D-Phe]-octreotide scintigraphy in functioning and non-functioning
      pituitary adenomas.
AB  - Scintigraphy with [111In-DTPA-D-Phe]-octreotide is a recently developed technique
      for imaging somatostatin receptors in many neuroendocrine tumors. A good
      correlation between high [111In-DTPA-D-Phe]-octreotide uptake and the response to
      octreotide therapy has been proved in TSH- and GH-secreting pituitary adenomas,
      while few and conflicting scintigraphic data on somatostatin receptors in non
      functioning tumors have been reported in the literature. The present study
      presents the results obtained with [111In-DTPA-D-Phe]-octreotide scintigraphy in
      thirteen patients with GH-secreting pituitary adenoma, four patients with
      inappropriate TSH-secretion and twelve patients with non-functioning pituitary
      adenoma. Twelve out of the 13 patients with GH-secreting pituitary adenomas had a
      positive scan; moreover, in 5/6 patients with a GH-secreting microadenoma (tumor
      size range 5-8 mm) a positive scan was found. Two TSH-secreting macroadenomas had
      a positive scan while a negative scan was obtained for a TSH-secreting pituitary
      microadenoma and in a patient with non-neoplastic, inappropriate secretion of
      TSH. Finally, only 2/12 patients with non-functioning pituitary adenoma showed a
      positive scan. In conclusion, [111In-DTPA-D-Phe]-octreotide scintigraphy is a
      useful tool to confirm the presence of somatostatin receptors in selected
      patients with GH- and TSH-secreting pituitary adenoma. The role of [111In-DTPA-D
      Phe]-octreotide scintigraphy in non-functioning pituitary tumors remains to be
      established, but it could be useful for octreotide treatment in patients who
      refuse surgery or who are poor surgical candidates.

PMID- 9002760
TI  - 111In-octreotide scintigraphy in pituitary adenomas.
AB  - This study reports on 111In-octreotide scintigraphy in 20 patients affected with
      pituitary adenomas, including tracer uptake ratios and in vitro
      immunohistochemical characterization of the matostatin receptor state. 111In
      octreotide uptake was already observed at 4 hours in 7/8 GH-secreting adenomas,
      in 5/7 non-secreting adenomas and in 1/5 prolactinomas. Concordance between the
      scan and the histochemical results was observed in all cases. The uptake ratios
      evaluated at 24 hours ranged from 2.3 to 4.2. The following conclusions were
      drawn: 1) 111In-octreotide is a suitable tracer to evaluate the somatostatin
      receptor state of pituitary adenomas; 2) Semi-quantitative measures of tracer
      uptake can be easily obtained with static planar scanning, but more refined
      techniques are needed for receptor kinetics evaluation; 3) This nuclear technique
      is a promising non-invasive tool to identify patients with somatostatin receptor
      positive pituitary adenomas who might potentially benefit from pre- and/or post
      surgery cold octreotide medical treatment.

PMID- 9002761
TI  - Scintigraphic assessment of pituitary adenomas and several diseases by indium-111
      pentetreotide.
AB  - The aim of this study was to identify the specific somatostatin receptors
      expressed by several tumors, utilizing 111In-octreotide, a long acting
      somatostatin analogue. We studied two different groups of patients: the first
      group was composed of 21 patients suffering from different pituitary adenomas,
      while the second group consisted of 12 patients affected by several different
      neoplasms. In vivo scintigraphy showed pentetreotide receptors only in large GH
      secreting adenomas and several macroadenomas. Concerning the endocrine activity
      of the adenomas, 111In-octreotide showed a good sensibility in detecting GH
      secreting tumors. In the second group, 111In-octeotride proved to be a good
      diagnostic tool to show carcinoid lesions which were missed by other
      complementary methodologies.

PMID- 9002762
TI  - Clinical relevance of 111In-octreotide scans in CNS tumors.
AB  - Sixty-six patients with a clinical and neuroradiological diagnosis of CNS tumors
      were evaluated by 111In-octreotide scintigraphy. Planar images were acquired at 2
      4 and 24 hours after the injection of 111-185 MBq of 111In-octreotide
      (Octreoscan, Byk-Gulden). In the positive scans the tumor/non-tumor ratio was
      evaluated using a standard ROI method, and an uptake index (U.I.) of the lesion
      was determined. In vitro binding assays were performed on frozen sections from
      surgical specimens from 17 patients. All 32 meningiomas demonstrated a positive
      111In-octreotide scan with a high U.I. Only 13 of 21 gliomas showed a positive
      scan, but the U.I. was significantly lower (p < 0.001 by "t"-test); one lymphoma
      showed a faint tracer uptake. All the other histotypes evaluated yielded negative
      scans. In all cases the receptorial pattern shown by the immunohistochemical
      staining technique was concordant with the scintigraphic results. 111In
      octreotide scintigraphy allowed a differential diagnosis of meningioma versus
      other CNS tumors in 6 patients (4 neurinomas, 1 brain metastasis of melanoma, 1
      lymphoma). In conclusion, 111In-octreotide scintigraphy is a promising tool to
      evaluate the SS receptorial pattern of CNS tumors and to increase the diagnostic
      specificity of conventional imaging providing useful information in selected
      cases for the therapeutic strategy.

PMID- 9002763
TI  - 111In-DTPA-D-Phe-1-octreotide scintigraphy of small cell lung cancer.
AB  - Twenty-one patients with small cell lung cancer (SCLC) were investigated with
      111in-octreotide (111-In-OCT) scintigraphs, 5 hours after the i.v. injection of
      111 MBq of the radiotracer. Whole-body and planar scintigraphy as well as SPECT
      of the thorax were required. The scintigraphic results were compared to those of
      other conventional diagnostic procedures used for the staging and follow-up of
      SCLC patients. 111In-OCT detected 86% (48/56) of the lesions already known at the
      time of scintigraphy, being positive for all 20 SCLC lesions and negative for one
      lung adenocarcinoma. 111In-OCT showed a high sensitivity for mediastinal
      metastases (94%) and good sensitivity for bone (75%) and abdominal lymph node
      metastases (71%). It did not detect 2 liver metastases but revealed 5 unknown
      lesions which were then confirmed by other diagnostic examinations. 111In-OCT was
      also effective in patients with low levels of NSE. Three patients received cold
      octreotide for seven days to investigate whether this treatment might affect SCLC
      imaging. Scans were performed before and after treatment. The 111In-OCT uptake
      increased in the cancer lesions while the fixation in normal tissues decreased,
      demonstrating enhancement of SCLC imaging following cold octreotide
      administration.

PMID- 9002764
TI  - 111In-octreotide scintigraphy in small cell lung cancer.
AB  - Somatostatin receptors have been identified on the cellular surface of a subset
      of patients with small cell lung cancer (SCLC) and may be associated with a less
      aggressive evolution of the tumor. Moreover, medical therapy with somatostatin
      analogues holds promise for neoplastic growth control. We performed planar
      imaging in 22 patients with histologically proven SCLC at 2-4 and 24 hours after
      the injection of 111-185 MBq of 111In-DTPA-octreotide (Octreoscan, Byk-Gulden).
      Tumor uptake was observed in 19 patients in both early and late scans, while 2
      patients previously treated with chemotherapy showed negative early and late
      scans. One patient had a positive early scan and a negative late scan. All the
      scintigraphic studies showed more extensive disease than expected by CT. No
      significant modification in tumor uptake of radiooctreotide was observed in three
      patients studied before and after chemotherapy. In conclusion, 111In-octreotide
      is a suitable radiopharmaceutical for the in vivo evaluation of the somatostatin
      receptors of small lung cancer. The prognostic and therapeutical implications of
      this nuclear technique must be further investigated, however.

PMID- 9002766
TI  - The role of 111In-octreotide scintigraphy in the detection of APUD tumours: our
      experience in eighteen patients.
AB  - 111In-Octreotide scintigraphy has been recently proposed as a sensitive technique
      for the detection of neuroendocrine tumours, based on the high radiotracer
      affinity towards the somatostatin receptors expressed by the APUD-system cells.
      In the present study, a group of 18 patients with carcinoid tumours and
      gastrointestinal (GI) apudomas was investigated to assess the accuracy of
      Octreotide scintigraphy in localizing primitive, recurrent or metastatic lesions.
      Both planar and SPECT studies were obtained 4 hours after the i.v. injection of
      111In-Octreotide (111 MBq); planar images were also carried out 24 hours later.
      In accordance with other authors, the sensitivity of the method was found to be
      very high (94%) in our group of patients; only in one case of nesidioblastosis
      was the scintigraphy negative. No differences in sensitivity were observed
      between the planar and SPECT studies, but the latter provided a better
      topographic localization of the neoplastic foci. It should be pointed out that in
      7 cases (3 primitive, 1 recurrent and 3 metastatic lesions) scintigraphy
      correctly localized the tumour, when the other morphological techniques, such as
      echography, computed tomography or magnetic resonance, failed. On the basis of
      our data, we believe that Octreotide scintigraphy should be the first study
      performed in the evaluation of patients affected by APUD tumours.

PMID- 9002765
TI  - SPECT imaging with 111In-octreotide for the localization of pancreatic
      insulinoma.
AB  - We evaluated the sensitivity of 111In-Octreotide scintigraphy in the diagnosis of
      pancreatic insulinoma in a selected number of patients. In addition, we compared
      the results of scintigraphy with those of other conventional diagnostic
      techniques. Seven patients with surgically confirmed insulinoma (< 1.5 cm in
      diameter) of the pancreas were studied. Before surgery, patients underwent
      arteriography with Ca-gluconate, CT scan, and 111In-Octreotide scintigraphy.
      111In-Octreotide scintigraphy showed a higher diagnostic specificity (85%) than
      selective arteriography (83%) or CT scan (57%). We conclude that 111In-Octreotide
      scintigraphy should always be performed before surgery in cases of pancreatic
      insulinoma and that a SPECT acquisition should be performed both 6 and 24 hours
      post-injection in order to increase the diagnostic sensitivity of the test.

PMID- 9002769
TI  - Whole body and tomographic scan with 111In-pentetreotide: preliminary data.
AB  - Since December 1993, in the 1st Nuclear Medicine Service of the University of
      Padua, eleven somatostatin-receptor scintigraphic studies with 111In-labelled
      pentetreotide have been performed. The patients (6 men and 5 women, age 28-68,
      mean 45 years) were affected by a variety of tumors which supposedly express
      somatostatin receptors: 2 meningotheliomatous meningiomas post-surgery; 2
      glucagonomas with liver metastases observed on CT; 2 patients with suspicion of
      insulinoma; 2 carcinoids, one after surgery; 1 ectopic-ACTH Cushing's syndrome; 1
      intracranial germinoma, post-surgery, in whom the study was requested to evaluate
      a doubtful finding of pulmonary metastatic lesion on CT; and 1 acromegaly
      showing, on MRI, and empty sella turcica occupied by and extraflexion of the
      lower portion of the chiasmatic cisterna without signs of adenoma and the
      sphenoidal sinus occupied by tissue wit inflammmatory characteristics.
      Somatostatin-receptor whole body scintigraphy was performed 4 and 24 hours after
      intravenous injection of 110 MBq 111In-pentetreotide (Octreoscan 111); spot
      images were acquired when judged necessary. In one case of glucagonoma, a
      tomographic scan (SPECT) was also performed to better evaluate the spatial
      relationship between the primitive pancreatic tumor and surrounding tissues.
      Focal accumulation of 111In-pentetreotide was scintigraphically detected in 5 of
      the 11 cases. Intense uptake of the radiopharmaceutical was observed in the
      meningiomas, in the glucagonomas with liver metastases, and in the case of
      acromegaly, corresponding to a GH-secreting adenoma. The negative scans seem to
      be true negative scans with the possible exception of one patient with a still
      unconfirmed suspicion of insulinoma, still not confirmed.

PMID- 9002767
TI  - 111In-octreotide scintigraphy in endocrine tumors. Preliminary data.
AB  - A large number of endocrine tumors express somatostatin receptors, and the use of
      radiolabeled somatostatin analogs has been recently introduced for their
      localization. Using in vivo scintigraphy with 111In-pentetreotide, primary tumor
      localizations were demonstrated in 3/3 carcinoids (2 intestinal carcinoids and 1
      lung ACTH-secreting carcinoid; in 2 patients liver metastases larger than 1 cm
      were visualized), in 1/1 GH-secreting pituitary macroadenoma, and in 1/1 thyroid
      localization of MTC. Bone and/or lymph node metastases were imaged in 2/4
      patients previously treated for MTC, with persistently high CT and CEA levels; in
      the other 2 patients the other scintigraphic techniques were also negative.
      Octreotide scintigraphy was negative in 2/2 insulinomas and in 2/2 ACT-producing
      pituitary adenomas. In 2 patients with carcinoid syndrome and 1 patient with
      Cushing syndrome due to ectopic ACTH, octreotide therapy induced a significant
      decrease in tumoral markers. Our preliminary data are in agreement with the
      results of larger series reported in literature: octreotide scintigraphy is a
      useful noninvasive tool to detect endocrine tumors expressing somatostatin
      receptors, particularly for carcinoids. It is of great use in the differential
      diagnosis of Cushing syndrome due to ectopic ACTH. Moreover, 111In-pentetreotide
      scintigraphy may be useful in selecting patients who may benefit from octreotide
      therapy to control hormonal hypersecretion effects.

PMID- 9002770
TI  - 111In-octreotide in the evaluation of autoimmune thyroid diseases.
AB  - Aim of our study was to evaluate the uptake of Indium-111 Octreotide (OCT) at the
      level of thyroid and orbits in autoimmune thyroid diseases. Nine patients with
      Graves' disease (GD) who were also affected with thyroid associated
      ophthalmopathy (TAO) and four patients with Hashimoto's thyroiditis (HT) were
      evaluated. A patient with lung cancer, presenting ophthalmopathy did not related
      to autoimmune dysthyroidism, was also studied. All patients with ophthalmopathy
      were evaluated by a Clinical Activity Score and an A-scan standardized
      echography. Multiple planar images were acquired over a 24-hour period after i.v.
      injection of 111 MBq of 111In-OCT. A SPECT study was also obtained in 7 patients
      five hours after the injection. A qualitative analysis was performed.
      Semiquantitative ratios comparing the counts on the thyroid with respect to
      background (T/BK) and on the orbits and brain with respect to the blood-pool were
      also obtained. Thyroid uptake of OCT was higher in GD with respect to HT, and was
      not related to the functional state of the gland. The highest T/BK ratio was
      observed at the 24 hour control. Intense orbital uptake was observed only in case
      where a clinically active ophthalmopathy was present.

PMID- 9002768
TI  - Somatostatin receptor imaging: a preliminary experience in forty-nine patients.
AB  - We report our experience with the 111In-pentetreotide scanning of 47 adult
      patients presenting with neuroendocrine tumors (n = 38) or malignant
      pheochromocytomas or related tumors (n = 9), and 2 children with metastatic
      neuroblastomas. A dynamic study was performed after i.v. administration of 50-190
      MBq of 111In-pentetreotide followed by a whole body scan at 1.5-4 hours and at 24
      hours. Where indicated, tomoscintigraphy or a dual isotope bone, liver or kidney
      scan was performed in order to improve the anatomical definition. Lesions were
      visualized in the earliest phases of the examination but contrast was enhanced on
      delayed images due to an improved signal to background ratio. In 9/49 patients,
      octreotide scan (OS) detected unknown tumors sites. On the other hand, the lesion
      uptake of 111In-pentetreotide varied, and not all the sites shown by other
      imaging modalities were visualised, probably due to differences in membrane
      receptor expression. In conclusion, OS can be useful in the diagnosis, follow-up
      and therapeutic management of neuro-endocrine tumors. Further investigations are
      required to assess the role of OS in other pathologies. Short title: Somatostatin
      receptor imaging.

PMID- 9002771
TI  - 111In-pentetreotide scintigraphy in the post-thyroidectomy follow-up of patients
      with medullary thyroid carcinoma.
AB  - Local and lymphnodal recurrences of medullary thyroid carcinoma (MTC) in
      thyroidectomy patients with elevated plasma levels of calcitonin and/or CEA can
      be detected using 111In-pentetreotide (Octreoscan: OCT) scintigraphy, although
      the sensitivity of this technique in localizing an intrathyroid recurrence of
      tumor is affected by the low target/non-target uptake ratio. The survival rate of
      patients with MTC, who have undergone thyroidectomy and who show evidence of a
      rise in plasma levels of calcitonin and/or CEA is closely linked to the number
      and localization of the metastases. However the role of conventional imaging
      techniques (X-rays, US, CT, and MR) in the follow-up after thyroidectomy is
      controversial. Numerous radiocompounds are currently being used to detect local
      and distant recurrences of MTC. The present study evaluated OCT and pentavalent
      99mTc-dimercapto-succinic-acid (99mTc-DMSA-V) scintigraphy performed in 13
      patients with a histologic diagnosis of MTC and in one with MEN 2A, all of whom
      had undergone thyroidectomy between 3 months and 15 years before. The patients
      also underwent 123I (NaCI) scintigraphy to evaluate the sites and extension of
      thyroidal remnants. 111In-pentetreotide scintigraphy was positive in 9/14
      patients (64%); the 99mTc-DMSA-V was positive in 5/14 patients (35%). 111In
      pentetreotide scintigraphy recognized 18 sites of abnormal uptake (12 in the
      neck); 9mmTc-DMSA-V detected 9 MTC recurrences in the same patients. In
      conclusion, 111In-OCT scintigraphy represents, in the authors' experience, a
      useful method, more sensitive than 9mmTc-DMSA-V, to detect MTC recurrences in
      patient follow-up post-thyroidectomy.

PMID- 9002772
TI  - 111In-octreotide scintigraphy in metastatic medullary thyroid carcinoma before
      and after octreotide therapy: in vivo evidence of the possible down-regulation of
      somatostatin receptors.
AB  - We have investigated the presence of somatostatin receptors on the cell surface
      of metastatic medullary thyroid carcinoma in vivo using 111In-Octreotide
      scintigraphy. Five patients were studied before and three months after therapy
      with octreotide (300-600 micrograms/day). After each 111In-Octreotide
      scintigraphy the target/background (T/B) radioactivity ratio was calculated for
      each detectable metastases. A total of 14/18 metastases showed a reduction in the
      T/B ratio after therapy, suggesting saturation or down-regulation of the
      somatostatin receptors on metastases induced by octreotide therapy. Patients also
      showed a reduction in serum calcitonin levels after therapy. We conclude that
      111In-Octreotide scintigraphy may be useful in medullary thyroid carcinoma to
      evaluate the rationale for somatostatin therapy and to monitor the effect of
      treatment.

PMID- 9002773
TI  - MIBG and radiolabeled octreotide in neuroendocrine tumors.
AB  - Two newly developed radiopharmaceuticals, [131I]metaiodobenzylguanidine (MIBG)
      and 111In-pentetreotide, are currently used for the diagnosis and therapy of
      neural crest tumors. They interact with characteristic features of these tumors,
      such as the active uptake-1 mechanism at the cell membrane and vesicles or
      neurosecretory granules in the cytoplasm, as well as the presence of specific
      receptors at the cell membrane. The role of MIBG and Somatostatin analogues in
      the management of neural crest tumors is reviewed. Other uses of these
      radiopharmaceuticals are mentioned. It is concluded that both 111In-pentetreotide
      and 123I/[131]MIBG are sensitive indicators of neural crest tumors, which have a
      complementary role. Unlike MIBG, 111In-pentetreotide is not specific for neural
      crest tumors, as scintigraphy is also positive in many other tumors, granulomas
      and autoimmune diseases. [131I]MIBG is effectively used for the therapy of
      several neural crest tumors; the biodistribution of 111In-pentetreotide at
      present does not allow radionuclide therapy using a beta emitting label. However,
      as an indicator of somatostatin receptors, 111In-pentetreotide scintigraphy may
      be a predictor of the response to palliative treatment with unlabelled
      octreotide. Recommendations for the use of these procedures are given.

PMID- 9002774
TI  - Radiolabeled somatostatin analog scintigraphy in medullary thyroid carcinoma and
      carcinoid tumor.
AB  - The aim of this study was to evaluate the effectiveness of a recently developed
      radiolabelled somatostatin analog (111In-pentetreotide) for the detection and
      localization of both medullary thyroid carcinoma (MTC) and carcinoid tumors, and
      to compare the results obtained with the results of 99mTc(V)-DMSA, and
      radioiodinated MIBG imaging. 111In-pentetreotide scintigraphy was performed in 9
      patients with MTC and in 9 patients with carcinoid tumor. Whole body and SPECT
      studies were performed at 4 and 24 hours post-injection. SMS scintigraphy gave a
      positive result in 5 out of 7 patients with proven MTC lesions, and in 7 out of 9
      patients with known lesions of carcinoid tumor. It gave a negative result in 2
      MTC patients with high levels of calcitonin but with no evidence of disease at
      conventional diagnostic modalities. The scintigraphic results were comparable
      with those obtained with 99mTc(V)-DMSA in MTC and were superior to those of
      radioiodinated MIBG in both MTC and carcinoid tumors. When compared with the
      modifications of calcitonin levels brought about by the acute administration of
      octreotide ("Octeotride test"), these correlated well in 8 out of 9 patients
      studied.

PMID- 9002775
TI  - Comparison of labeled MIBG and somatostatin analogs in imaging neuroendocrine
      tumors.
AB  - In 10 patients with histologically proven neuroendocrine tumors (4 carcinoids, 4
      pheochromocytomas, 1 medullary thyroid cancer and 1 Merkel tumor) the results of
      radiolabeled metaiodobenzylguanidine (MIBG) and somatostatin analogs were
      compared. A total of 24 tumor lesions was detected on standard imaging studies.
      MIBG scintigraphy correctly localized 12 (50%) of these lesions which were
      observed in 5 patients (4 with pheochromocytoma and 1 with carcinoid tumor).
      Scintigraphy using labeled somatostatin analogs correctly localized 21 (87%)
      lesions which occurred in 8 patients (4 with carcinoid, 2 with pheochromocytoma,
      1 with medullary thyroid cancer and 1 with Merkel tumor). Concordant
      scintigraphic results were obtained in 1 patient with carcinoid and 2 with
      pheochromocytoma. In conclusion, although this series was limited, our results
      suggest that MIBG is more accurate than somatostatin analogs in imaging
      pheochromocytoma. Conversely, somatostatin analogs are more accurate than MIBG in
      detecting other neuroendocrine tumors such as carcinoids.

PMID- 9002776
TI  - Ten years of experience with MIBG applications and the potential of new
      radiolabeled peptides: a personal overview and concluding remarks.
AB  - The international workshop on metaiodobenzylguanidine (MIBG) and radiolabeled
      somatostatin analogs held in Rome in June, 1994 addressed a wide range of topics
      which might be classified into five broad general themes: Theme 1. The role of
      MIBG for the location of neuroendocrine tumors. A) The range of tumors in which
      MIBG scintigraphy is effective (pheochromocytomas, neuroblastoma, chemodectoma
      and other APUDomas). B) The increasing popularity of 123I as a radiolabel for
      MIBG (potential advantages in planar and SPECT imaging). C) MIBG as the prototype
      of a family of radiopharmaceuticals exploiting the biogenic amine uptake and
      storage mechanisms. (Other radiohalides 124I, 125I, 87Br, 211At, 18F; other PET
      radiopharmaceuticals such as 11C-epinephrine, 11C-hydroxyephedrine). Theme 2. The
      role of MIBG as an in vivo scintigraphic probe of the sympathetic nervous system.
      A) Cardiac sympathetic innervation (in cardiomyopathy, myocardial infarction, and
      as a prognostic index for cardiac transplantation). B) Pulmonary MIBG uptake as
      index of pulmonary endothelial/sympathetic function (MIBG by both the intravenous
      and inhaled routes of administration). Theme 3. MIBG for the radiopharmaceutical
      therapy of neuroendocrine tumors. A) Treatment of neuroblastoma early in the
      natural history of the disease (MIBG therapy as initial management, MIBG therapy
      combined with other modalities--e.g., chemotherapy and bone marrow
      transplantation). Theme 4. The role of radiolabeled somatostatin analogs for the
      location of neuroendocrine and other tumors. A) The range of tumors in which
      somatostatin receptor radiopharmaceutical scintigraphy is effective (pituitary
      tumors, central nervous system tumors, carcinoids, islet cell tumors, medullary
      thyroid carcinoma, small cell lung cancer, APUDomas). B) The superiority of 111In
      over 123I as a radiolabel (the future of potential 99mTc and other labels). C)
      Somatostatin receptor scintigraphy in autoimmune and other disorders. D)
      Pentetreotide as the prototype of a wide range of radiolabeled peptides as
      radiopharmaceuticals for the in vivo depiction of the receptors for peptide
      hormones, lymphokines, paracrine and other information transmitting molecules
      (the general concepts include the use of long-acting, slowly degraded analogs and
      the development of generally applicable labeling techniques. Examples include
      123I-ANF, labeled interleukins and other lymphokines). Theme 5. Comparisons of
      MIBG and pentetreotide scintigraphy for the location of neuroendocrine tumors. A)
      The range of neuroendocrine and other tumors (e.g., pheochromocytomas,
      neuroblastomas, carcinoids, islet cell tumors and other APUDomas).

PMID- 9002779
TI  - Ebola haemorrhagic fever. A summary of the outbreak in Gabon.

PMID- 9002777
TI  - Chagas disease. Interruption of transmission.

PMID- 9002778
TI  - Influenza.

PMID- 9002780
TI  - Health and selected socioeconomic characteristics of the family: United States,
      1988-90.
AB  - National estimates of average annual health indexes for the civilian
      noninstitutionalized population of the United States are presented in this report
      according to selected socioeconomic characteristics of the family. These
      estimates are based on data from the National Health Interview Survey (NHIS) in
      1988, 1989, and 1990. Health indexes presented include percent limited in
      activity; percent with fair or poor respondent-assessed health status, restricted
      activity days, bed disability days, work-loss days, and school-loss days; percent
      with a physician contact in past year; numbers of annual physician contacts per
      person per year; percent with a hospital episode in the past year; days per short
      term hospital stay; and incidence of acute conditions. This report includes the
      findings that persons living by themselves reported a higher percent of
      limitations in activity, high rates of disability days, more physician contacts
      per year, and a higher incidence rate from acute conditions than all persons 45
      64 years of age. Persons in all four age groups reported higher percents with
      limitations of activity and higher percents with fair or poor health status in
      families in which the educational level of the responsible family adult member
      was less the 12 years than in families where the responsible adult was better
      educated. Both males and females, and white persons and black persons, in each of
      the age groups 18 years and over who were living with a spouse reported lower
      percents of limitations in activity than did persons living in other family
      relationships.

PMID- 9002781
TI  - The role of the electric toothbrush in the control of plaque and gingivitis: a
      review of 5 years clinical experience with the Braun Oral-B Plaque Remover [D7].
AB  - The Braun Oral-B Plaque Remover (D7) (previously known as D5) is a well
      established electric toothbrush available worldwide. It has a round brush head
      with a diameter of 13 mm, with bristle tufts arranged in three circular rings,
      and an oscillating/rotating action. Since its introduction in 1991, a significant
      number of well designed clinical investigations have been published comparing the
      D7 with manual toothbrushes, as well as with other electric devices. A review of
      the findings from these various studies indicates that while both the D7 and
      manual toothbrushes effectively remove plaque and improve gingival condition, the
      efficacy of the D7 is clearly greater than that of the manual toothbrush. It is
      suggested that this advantage is related in particular to greater efficiency in
      interproximal, vestibular and lingual sites. Compared to other electric
      toothbrushes, there is evidence that the D7 also offers greater efficacy, but
      this requires clarification in further clinical investigations. It is concluded
      that the greater efficacy of the D7 over that of a manual toothbrush, together
      with the motivational effect that has been shown to be associated with electric
      toothbrush use, should offer potential for improved oral hygiene control.

PMID- 9002782
TI  - The development of the Braun Oral-B Ultra Plaque Remover: an in vitro robot
      study.
AB  - PURPOSE: To assess the efficacy of a new brush head design and brushing action
      using a novel robot system which simulates normal clinical toothbrush use. The
      system allows developments in toothbrush design to be assessed prior to embarking
      on expensive and time consuming clinical trials. MATERIALS AND METHODS: Using
      this system, the efficacy of a new brush head design combined with a modified
      brushing speed, was compared with the clinically established Braun Oral-B Plaque
      Remover (D7 handle and EB5 brush head). RESULTS: A combination of a new brush
      head (EB9) with longer tufts of bristles designed to improve interdental
      penetration, and an increased frequency of bristle movement (63Hz, 3,800 strokes
      per minute - D9 handle) was associated with significantly greater removal of
      artificial plaque. Visual observation of typodonts suggested that this increased
      efficacy is related to greater removal of plaque from interdental surfaces and
      occlusal fissures. These results suggest that the D9/EB9 prototype electric
      toothbrush is suitable for further investigation and clinical evaluation.

PMID- 9002783
TI  - The dentin abrasivity potential of a new electric toothbrush.
AB  - PURPOSE: To evaluate the safety of the new Braun Oral-B Ultra Plaque Remover (D9)
      electric toothbrush, by measuring its abrasivity to dentin and comparing it with
      the abrasivity of a standard ADA reference toothbrush. MATERIALS AND METHODS:
      Dentin abrasion was measured by a radiotracer technique, using a modification of
      the ADA recommended methodology. A V-8 cross-brushing machine, set to make 1,500
      strokes, was used for the standard reference ADA toothbrush. Because the electric
      toothbrush would not fit on the V-8 machine, the brushing procedure was modified
      so the D9 was suspended from a ring stand in a shaker bath set to give 44
      strokes/minute. Both toothbrushes were tested with a slurry of 25 g of Crest
      dentifrice in 40 ml of water. After both toothbrushes had been tested for 8.5
      minutes, samples of the slurry were put in a scintillation counter and mean net
      counts per minute (cpm) per gram of slurry were calculated. RESULTS: The mean
      relative dentin abrasion (RDA) of the Braun Oral-B Ultra Plaque Remover (D9)
      brush was found to be low (16) and was markedly less than that of the ADA
      reference brush (100).

PMID- 9002784
TI  - A laboratory investigation of stain removal from enamel surface: comparative
      efficacy of three electric toothbrushes.
AB  - PURPOSE: To evaluate in a controlled laboratory investigation the efficacy of
      three electric toothbrushes with respect to removal of extrinsic dental stain
      from labial enamel surfaces of bovine permanent central incisors. MATERIALS AND
      METHODS: Enamel specimens were treated to produce a uniformly stained pellicle
      film. Staining was assessed photometrically, before and after brushing 16
      specimens per group for 4.5 minutes with either the Braun Oral-B Plaque Remover
      (D7), the Braun Oral-B Ultra Plaque Remover (D9) or a high frequency electric
      toothbrush. A manual brush with the ADA reference abrasive was used as a positive
      control, and this was compared with the three electric toothbrushes, using a
      dentifrice slurry prepared from Crest toothpaste. Tension on the enamel specimens
      was set at 150 g, except for the high frequency toothbrush which was set at the
      manufacturer's recommended tension of 50 g. Stain removal was expressed as a
      cleaning ratio (CR), where larger values represented greater removal of stained
      pellicle. RESULTS: Compared with the ADA control (CR = 100), the D9 was the most
      effective (CR = 98) removing significantly more stain (P < 0.05) than the D7 (CR
      = 74). The high frequency toothbrush was found to be the least effective (CR =
      48), removing significantly less stain than any of the other toothbrushes (P <
      0.05).

PMID- 9002785
TI  - A comparative clinical study of extrinsic tooth stain removal with two electric
      toothbrushes [Braun D7 and D9] and a manual brush.
AB  - PURPOSE: To evaluate the efficacy and safety of two oscillating/rotating
      toothbrushes, (Braun Oral-B Plaque Remover-D7 and Braun Oral-B Ultra Plaque
      Remover-D9) and a manual toothbrush with respect to removing extrinsic dental
      stain. MATERIALS AND METHODS: This randomized, three-way cross-over study
      investigated 24 subjects entering the trial, which was divided into three, 5-day
      periods. Over the first 4 days of the study, an intense chlorhexidine/tea rinsing
      regimen was employed to induce extrinsic tooth staining. On day 5, each subject
      was assessed for tooth stain; they then brushed for a total of 2 minutes with one
      of the three randomly allocated toothbrushes. Stain evaluations were repeated
      after 30 seconds, 1 and 2 minutes brushing, with the intensity of stain, area of
      stain and number of sites with < 10% stained tooth area, being recorded at each
      assessment. RESULTS: Analysis of the results showed that the two electric
      toothbrushes were significantly better at removing stain than the manual
      toothbrush. In addition, the D9 was consistently more effective than the D7, with
      the difference with respect to stain area achieving statistical significance (P <
      0.05) after 2 minute's brushing. All three brushes were found to be safe, and
      there was no evidence of any soft or hard tissue abrasion. It was concluded that
      the oscillating/rotating electric toothbrushes were more effective in removing
      extrinsic dental stain than a manual brush, and that compared with the D7, the
      newly designed Braun Oral-B Ultra Plaque Remover has an increased potential for
      stain removal.

PMID- 9002786
TI  - Toothbrushing duration and plaque removing efficacy of electric toothbrushes.
AB  - PURPOSE: To test the plaque removing efficacy of three different toothbrushes in
      relation to duration of toothbrushing. MATERIALS AND METHODS: The brushes studied
      were the Sonicare, the Braun Plak Remover (D7), and a modified Plak Control with
      increased speed (D9). Part 1 of the study was divided into four experiments which
      differed only in respect to the brushing time. The available times were 15, 30,
      45, 60 seconds per quadrant. After 48 hours plaque accumulation, all subjects (n
      = 22) were brushed professionally using at random a brush in one quadrant
      (without toothpaste). Part 2 was a 3-way cross-over design in which the same
      three brushes were tested. In total 49, subjects participated. They were given a
      brief instruction on the use of each toothbrush and were allowed to get
      familiarized with each brush during a 2-week period. After 48 hours plaque
      accumulation, they brushed in a random order the four quadrants, each with a
      different brushing time (15, 30, 45, 60 seconds). The amount of dental plaque was
      evaluated pre- and post-brushing by means of the Silness & Loe plaque index at
      six sites around each tooth investigated. RESULTS: The results of Part 1 and 2
      showed an increase in efficacy for all brushes varying from 1 minute per quadrant
      to 4 minutes per quadrant. In Part 1, the D7 was more effective than the Sonicare
      brush at 15, 20, 45 seconds whereas the D9 was more effective at all four
      brushing times. In Part 2, both the D7 and D9 were more effective than the
      Sonicare at the 2-minute brushing time. These differences were mainly caused by a
      greater plaque removal from the approximal areas.

PMID- 9002787
TI  - Quantitative contribution of the collagen network in dentin hybridization.
AB  - PURPOSE: To determine the quantitative contribution of dentin hybridization to
      bonded assembly strength and demonstrate the micromorphology of the interface
      with and without collagen present. MATERIALS AND METHODS: Four groups of 10 molar
      teeth were finished to a 320 grit dentin smear layer. Two groups served as
      controls and two experimental groups were subjected to collagenase digestion of
      the collagen exposed by acid conditioning. All-Bond 2 and Amalgambond were used
      to bond Bisfil and Epic resin composite, respectively. Stored in water at 37
      degrees C for 24 hours the assemblies were tested in a shear mode at a crosshead
      speed of 5 mm/minute. Means and standard deviations were subjected to analysis
      for statistical significance. Twenty four teeth in four groups were examined by
      scanning (SEM) and transmission electron microscopy (TEM) for the relationship
      between resin and conditioned dentin with and without the collagen network.
      RESULTS: All-Bond 2 and Amalgambond controls were 28.41 +/- 3.9 and 19.04 +/-
      5.96 MPa, collagenase-treated groups scored 26.43 +/- 2.90 and 19.70 +/- 4.25 MPa
      respectively. No significant difference existed between the control and
      experimental groups. SEM showed an intertubular collagen network with patent
      tubules and a pronounced porous, irregular dentin topography following collagen
      digestion. A distinct hybrid zone and tubular penetration was observed but the
      collagenase-treated specimens showed only resin in the tubules and their lateral
      extensions. TEM confirmed the absence of a distinct hybrid zone in the
      collagenase groups with a tight, gap-free junction between the resin and the
      undemineralized dentin. An electron dense zone (< 50 nm) at the leading edge of
      conditioning was observed for All-Bond 2 and Amalgambond groups. It was concluded
      that the resin-reinforced or hybridized, collagenous network does not detract
      from, nor contribute any significant quantitative value per se to dentin bonding
      with the systems tested.

PMID- 9002788
TI  - Sealing performance of Scotchbond Multi-Purpose-Z100 in Class II restorations.
AB  - PURPOSE: To evaluate the sealing ability of Class II Scotchbond Multi
      Purpose/Z100 composite restorations placed under in vivo and in vitro conditions.
      MATERIALS AND METHODS: For the in vivo part, Class II preparations were cut in
      posterior teeth which were scheduled for extraction for periodontal reasons. The
      cervical margins ended in dentin-cementum, 1 mm below the CEJ. The teeth were
      extracted after 2-3 months of clinical service. The in vitro part was performed
      in extracted posterior teeth, free from restorations and caries, following the
      same in vivo protocol. The in vivo and in vitro samples were processed and
      evaluated for marginal leakage. RESULTS: Leakage by dye penetration was observed
      at the cervical margins in 70% of the in vivo and in 50% of the in vitro
      specimens. All in vivo samples with no leakage at the cervical margin were
      restored where the adjacent interproximal tooth was missing. In more than 40% of
      the restorations placed in vivo, leakage was also found at the occlusal margins.
      Statistically significant differences were found at the cervical margins between
      in vivo and in vitro groups (P < 0.05). The in vitro samples can be of only
      limited value in predicting clinical performances of an enamel-dentin bonding
      system in Class II restorations.

PMID- 9002790
TI  - Dimensional stability of two visible light-cured indirect inlay/onlay resin
      composite materials.
AB  - PURPOSE: To evaluate the dimensional stability over time of two visible light
      cured indirect inlay/onlay resin composites. MATERIALS AND METHODS: Twenty
      working dies of a Class II preparation were constructed in type IV die stone from
      impressions of a master metal die. Working dies were randomly divided into two
      groups of 10 with Class II resin composite inlays fabricated using Brilliant
      Dentin (n = 10) and Triad inlay material (n = 10). Inlays were seated on the
      master metal die 1, 3 and 10 days after fabrication and resin replicas were made
      of the proximal gingival margin surface which were gold-sputtered and used for
      the measurement of gingival margin gap distances at four locations using an SEM
      micron measurement system. RESULTS: Triad inlays mean gingival margin gap
      measurement was significantly (P < 0.05) greater at 10 days versus 1 day.
      Brilliant Dentin inlays had no significant mean gingival margin gap measurement
      differences between any time periods. As a material, Triad inlays had
      significantly less gingival margin gap distances than the Brilliant Dentin inlays
      at all three time intervals.

PMID- 9002791
TI  - Bond strength of an adhesive polymerized under nitrogen.
AB  - PURPOSE: To evaluate the use of nitrogen, in conjunction with visible light
      polymerization, for improving composite-to-dentin bond strengths. MATERIALS AND
      METHODS: Composite cylinders were bonded to dentin with Scotchbond Multi-Purpose.
      Immediate (Groups 1-4) and 24-hour (Groups 5-8) strengths were determined for the
      following two adhesive application and two polymerization techniques: Groups 1 &
      5: gentle air thinning of adhesive and polymerization with conventional visible
      light curing (VLC) unit; Groups 2 and 6: aggressive air thinning of adhesive and
      conventional VLC; Groups 3 and 7: gentle air thinning of adhesive and
      polymerization in nitrogen environment with modified VLC unit; and Groups 4 and
      8: aggressive air thinning of adhesive and polymerization in nitrogen environment
      with modified VLC unit. RESULTS: The immediate bond strengths (MPa) were: Group
      1: 15.1 +/- 1.8, Group 2: 6.1 +/- 2.1, Group 3: 17.8 +/- 3.1, Group 4: 15.8 +/-
      2.0. The 24-hour strengths were: Group 5: 26.7 +/- 4.4, Group 6: 13.5 +/- 7.5,
      Group 7: 24.1 +/- 5.7, Group 8: 26.4 +/- 4.3. Visible light polymerization of a
      thinned layer of adhesive resin in a nitrogen environment produced significantly
      higher immediate and 24-hour bond strengths than when compared to visible light
      polymerization in ambient air.

PMID- 9002789
TI  - 2-year clinical evaluation of Class I posterior composites.
AB  - PURPOSE: To clinically evaluate different brands of resin composites in Class I
      restorations. MATERIALS AND METHODS: A total of 120 Class I cavities were
      prepared in permanent molars and restored with four posterior resin composites:
      Clearfil Photo Posterior, Z100, Herculite XR, and Heliomolar RO. The restorations
      were evaluated at baseline, 1 and 2 years using the USPHS criteria. RESULTS:
      After 1 year, Z100 restorations were rated Alfa in all tested criteria. Clearfil
      PP, Herculite XR and Heliomolar RO showed slight changes in color match, anatomic
      form, and marginal adaptation. After 2 years, no significant difference was found
      in the evaluation of cavosurface discoloration for all tested materials. Z100 and
      Herculite XR were significantly more color stable than Clearfil PP and Heliomolar
      RO. The anatomic form evaluation showed Z100 with a significantly higher value
      than other groups. Heliomolar RO revealed the lowest percentage of marginal
      adaptation.

PMID- 9002793
TI  - The interaction of adhesive systems with human dentin.
AB  - PURPOSE: To investigate the interaction of six experimental and commercial
      bonding systems with dentin in vivo. MATERIALS AND METHODS: One-Step, Clearfil
      Liner Bond 2, OptiBond, Permagen with 10% phosphoric acid, Permagen with 35%
      phosphoric acid, and Prime & Bond were applied in standard Class I occlusal
      cavities in premolars scheduled for extraction for orthodontic reasons, combined
      either with a self-cured or with a light-cured resin composite. The teeth were
      carefully extracted 5 minutes after resin polymerization and fixed in 2.5%
      glutaraldehyde. After fixation, the specimens were dehydrated, sectioned, and
      processed for field-emission SEM. RESULTS: Although some systems produced gap
      free intact interfaces in specific specimens, all of them showed detachment at
      the transition between the resin-dentin interdiffusion zone and the fluid resin
      placed over it. It was apparent that the presence of air-bubbles and/or thick
      layers of polymerized-filled fluid resin resulted in less frequent separation
      areas at the resin-dentin interface, providing support for the concept of the
      elastic cavity wall. It was also confirmed that some dentin adhesive systems do
      not form a thick layer over the dentin, otherwise the resin composite would not
      have penetrated the dentin tubules.

PMID- 9002792
TI  - The overwet phenomenon: a transmission electron microscopic study of surface
      moisture in the acid-conditioned, resin-dentin interface.
AB  - PURPOSE: To identify ultrastructural features resulting from possible primer
      water interaction when a two-bottle, acetone- and alcohol-based dentin adhesive
      (All-Bond 2) was applied to acid-conditioned dentin in the presence of excess
      water. MATERIALS AND METHODS: Three groups (3-second dry, visibly moist,
      overwet), each comprising eight dentin discs prepared from human third molars,
      were established and bonded with All-Bond 2 under different degrees of surface
      moisture. Variations in the ultrastructural appearance of the resin-dentin
      interface from laboratory demineralized and epoxy resin embedded disc pairs were
      examined either with en bloc ruthenium red pre-staining alone or further stained
      with uranyl acetate and lead citrate. RESULTS: Displacement of water by the
      volatile primer solvents resulted in the formation of a layer of resin
      impregnated dentin in the three groups. Interaction of the primer with water
      following the evaporation of the volatile primer solvents resulted in phase
      separation of the primer components. Ultrastructural features observed within the
      previously water-filled blister-like spaces on the dentin surface in the visibly
      moist and overwet groups recapitulated what was observed within partially water
      filled dentin tubules in the 3-second dry group. The overwet phenomenon appeared
      to be a result of emulsion polymerization, involving irreversible interaction of
      water-soluble bifunctional primer components with those that are water
      immiscible, through the formation of micelles, resulting in the absence of total
      interfacial integrity.

PMID- 9002794
TI  - Microleakage of amalgam restorations using dentin bonding system primers.
AB  - PURPOSE: To evaluate and compare in vitro microleakage of etched and non-etched
      Class I amalgam restorations lined with various dentin bonding system primers to
      amalgam restorations with or without a Copalite liner. MATERIALS AND METHODS:
      Class I amalgam preparations were made in 140 extracted molars and divided into
      14 groups of 10 teeth each. Permite C dispersed phase alloy restorations were
      placed after the following treatments: Group 1: No liner; Group 2: Lined with two
      coats of Copalite; Group 3(A): Lined with Amalgambond AA and 3(B): Etched with
      35% Ultra-etch and lined with Amalgambond AA; Group 4(A): Lined with Scotchbond
      Multi-Purpose Primer and 4(B): Etched and lined with the primer; Group 5(A):
      Lined with ProBond and 5(B): Etched and lined with the primer; Group 6(A): Lined
      with All-Bond 2 Primer A & B and 6(B): Etched and lined with the primer; Group
      7(A): Lined with OptiBond and 7(B): Etched and lined with the primer; Group 8(A):
      Lined with Permagen Primer and 8(B): Etched and lined with the primer. All
      primers were applied per manufacturers' specifications. After storage in water
      for 24 hours, all restorations were polished and then aged in water at 37 degrees
      C for 90 days. The specimens were then thermocycled for 300 cycles at 5 degrees C
      and 55 degrees C in basic fuchsin dye with a 30-second dwell time, mounted in
      epoxy rings, sectioned longitudinally, mesiodistally and buccolingually into four
      sections, then evaluated at x100 and the extent of dye penetration at the
      tooth/amalgam interface scored (two scores for each section, eight for each
      specimen). RESULTS: The unlined and Copalite-lined groups and all non-etched
      groups showed considerable marginal leakage. All the etched restorations were
      significantly more effective in reducing microleakage than the non-etched, no
      liner and Copalite-lined groups. Etching prior to application of the primers is
      significantly more effective than nonetching, however the effectiveness of the
      primer alone to seal the dentin needs to be evaluated. Overall, Amalgam-bond AA
      had the least microleakage of all the groups.

PMID- 9002795
TI  - Fabrication of an anterior resin composite bridge with polyethylene fiber
      reinforcement.

PMID- 9002796
TI  - Effect of an antiseptic mouthrinse on salivary microbiota.
AB  - PURPOSE: To evaluate the effect of rinsing with original formulation Listerine
      Antiseptic (LA) on the level of viable salivary bacteria for periods up to 1
      hour. MATERIALS AND METHODS: In this double-blind, controlled, cross-over study,
      unstimulated saliva was collected from 25 subjects, serially diluted, and
      cultured on selective and non-selective media under aerobic and anaerobic
      conditions. Streptococci, Veillonella sp., and total aerobic and anaerobic flora
      were enumerated just prior to and 2, 15, 30, and 60 minutes after rinsing for 30
      seconds with either 20 ml of LA or a 5% hydroalcohol control rinse. RESULTS:
      After the control rinse, total flora cultivated on MM10 agar exhibited a non
      significant (P > 0.05) 10%-20% decrease relative to baseline. In contrast,
      rinsing with LA resulted in a significant (P < 0.05) 60%-65% decrease from
      baseline in all four microbial groups at 2 minutes; except in the case of
      Veillonella, the significant decreases were sustained up to 60 minutes. Total
      Listerine group aerobic, anaerobic and streptococcal counts were significantly
      lower than placebo (P < 0.05). The significant reduction in salivary bacterial
      levels seen in the Listerine group for up to 60 minutes suggests that this
      antiseptic mouthrinse may have use clinically as a pre-procedural rinse to
      decrease the level of viable microorganisms in aerosols generated during dental
      procedures.

PMID- 9002797
TI  - Microleakage of Class V composite, resin sandwich, and resin-modified glass
      ionomers.
AB  - PURPOSE: To evaluate in vitro the extent of microleakage of Class V cavities
      restored with composite, and resin-modified glass ionomers. MATERIALS AND
      METHODS: Class V cavities were prepared in 35 extracted teeth and randomly
      divided into seven groups of five teeth each (10 restorations in each group).
      Group 1: Scotchbond Multi-Purpose Adhesive (SMP) and restored with Z100 resin
      placed with an incremental technique, Group 2: Lined with GC Fuji lining LC and
      restored with SMP and Z100. Group 3: Based with Fuji II light-cured glass ionomer
      restorative and restored with SMP and Z100. Group 4: Lined with Vitrebond and
      restored with SMP and Z100. Group 5: Based with Vitremer and restored with SMP
      and Z100. Group 6: Restored with Fuji II LC. Group 7: Restored with Vitremer. The
      teeth were subjected to thermocycling, stained with silver nitrate, then
      longitudinally sectioned. Dye penetration at the tissue/restoration interface was
      scored based upon the extent and location of the precipitated silver. RESULTS:
      All groups demonstrated minimal or no microleakage at both the enamel and
      gingival sites.

PMID- 9002798
TI  - Effect of low-viscosity resins on the performance of dental adhesives.
AB  - PURPOSE: To determine whether the use of low-viscosity intermediate resins (LVR)
      reduces microleakage of dental adhesive systems. MATERIALS AND METHODS: Wedge
      shaped Class V cavities were prepared in sound extracted molars. Occlusal margins
      were in enamel and gingival margins were in dentin/cementum. Five adhesive
      systems (All-Bond 2, Clearfil Liner Bond 2, OptiBond, Prime & Bond and Scotchbond
      Multi-Purpose) were applied to the preparations strictly according to
      manufacturers' directions on one side of the tooth and with the addition of LVR
      (OptiBond FL Adhesive or Protect Liner F) on the other. All cavities were
      restored with Z100 resin composite. Specimens were then stored in water at 37
      degrees C for 24 hours, thermocycled 800x, stained with silver nitrate,
      sectioned, and evaluated for leakage. Marginal penetration of silver nitrate was
      scored on 0-3 scale. RESULTS: Statistical analysis (Kruskal-Wallis non-parametric
      ANOVA) revealed a significant difference (P < 0.0001) in leakage at dentin
      margins. Multiple pairwise comparisons of control groups revealed considerable
      overlapping between groups, but with a trend toward less leakage by OptiBond and
      Clearfil Liner Bond 2. Leakage of Scotchbond Multi-Purpose was significantly
      reduced when Protect Liner F was used.

PMID- 9002799
TI  - Bond strengths to enamel and dentin with indirect and direct resin composites.
AB  - PURPOSE: To investigate the differences in shear bond strengths between indirect
      and direct resin composites attached to enamel and dentin. MATERIALS AND METHODS:
      Sixty human molar teeth stored in distilled water since extraction were used in
      this study. Thirty of the teeth were prepared to form a flat enamel surface
      ground to 600 grit and 30 of the teeth were prepared to form a flat dentin
      surface ground to 600 grit. Cylinders constructed from Triad indirect resin
      composite were bonded to 15 enamel and 15 dentin surfaces and additional
      cylinders constructed from TPH direct resin were bonded to the remaining 15
      enamel and 15 dentin substrates. Bond strengths were determined by shearing the
      specimens with an Instron testing machine. RESULTS: Mean shear bond strengths
      observed in this study were: Triad to enamel, 27.64 +/- 7.35 MPa; TPH to enamel,
      27.43 +/- 3.37 MPa; Triad to dentin, 21.83 +/- 3.10 MPa; and TPH to dentin, 21.27
      +/- 4.85 MPa. Two-way ANOVA demonstrated that significant differences existed
      between the four test groups and that this difference was primarily related to
      the surface to which the cylinders were attached (P = 0.000). No significant
      differences were discovered in shear bond strengths between restorative materials
      (P = 0.767) or between restorative materials bonded to a specific, common surface
      (P = 0.891). Turkey's post hoc test demonstrated that the shear bond strength of
      Triad to enamel was significantly greater than the shear bond strength of either
      Triad to dentin (P = 0.012) or TPH to dentin (P = 0.005). This test also pointed
      out that the shear bond strength of TPH to enamel was significantly greater than
      the shear bond strength of either TPH to dentin (P = 0.007) or Triad to dentin (P
      = 0.016). Finally, it was noted that the shear bond strength of Triad to enamel
      was essentially the same as TPH to enamel (P = 1.000) and that the bond strength
      of Triad to dentin was essentially the same as TPH to dentin (P = 0.990).

PMID- 9002800
TI  - The overwet phenomenon: a scanning electron microscopic study of surface moisture
      in the acid-conditioned, resin-dentin interface.
AB  - PURPOSE: To study with the scanning electron microscope the interfacial
      phenomenon that occurred in the presence of excessive surface moisture following
      the application of an acetone-based adhesive to acid-conditioned dentin.
      MATERIALS AND METHODS: Specimens consisted of flat dentin discs that were divided
      into three groups based upon the status of remaining surface moisture: (1) 3
      second dry group, (2) blot-dry group, with the conditioned dentin surface
      remaining shiny as opposed to matte, and (3) overwet group: an additional 40 mL
      of distilled water spread thin on the dentin surface after blot-drying. Polished
      resin-dentin interfaces were brought into relief using plasma-etching and
      examined without further embedding. RESULTS: Although a hybrid layer was observed
      in all three groups, there was (1) a sequential deterioration of the bonded
      assembly along the hybrid layer-resin interface, and (2) loss of complete tubular
      seal as the quantity of surface moisture increased. Intratubular resin globules
      were observed beneath short resin plugs in the 3-second dry group. Small,
      isolated blister-like spaces, trapped within the resin layer, were observed along
      the surface of the hybrid layer in the blot-dry group, while similar, but larger
      spaces were found in the overwet group. The blister-like spaces, which were often
      continuous with incompletely sealed tubular orifices, were partially filled with
      extraneous resin globules dispersed within an amorphous matrix.

PMID- 9002801
TI  - Dual application of dentin bonding agents: effect on bond strength.
AB  - PURPOSE: To evaluate the effect of a dual application of dentin bonding agents
      (DBA) on their shear bond strength on dentin with intermediate application of a
      provisional cement. MATERIALS AND METHODS: Freshly prepared flat dentin surfaces
      of human teeth were coated with a first layer of one of various dentin bonding
      agents (All-Bond 2, ART Bond, Syntac or an experimental DBA called P-Bond). After
      curing the DBA, a provisional cement (Temp Bond, Freegenol or Fermit, a soft
      provisional diacrylate) was applied to the bonded dentin surface. After 24 hours,
      the provisional cement was removed and the dentin surface scrubbed with pumice. A
      second application of the same DBA together with a composite cylinder followed.
      After curing and 1,500 thermal cycles with constant imitation of intrapulpal
      pressure, shear bond strengths were measured. RESULTS: Compared to a single
      application of dentin bonding agents following Temp Bond treatment (SBS in MPa:
      Syntac: 0.86 +/- 1.75, ART Bond: 0.26 +/- 0.47, P-Bond: 14.90 +/- 4.51)
      application of DBAs prior to use of Temp Bond as well as after its removal seems
      to be very beneficial to shear bond strength values (SBS in MPa: Syntac:13.36 +/-
      4.70, ART Bond: 16.34 +/- 5.02, P-Bond: 19.04 +/- 2.01). Independent from the
      provisional cement, the values after serial application of P-Bond provided
      consistently high bond values which were not statistically different (Kruskal
      Wallis, P > 0.05) from values of P-Bond on fresh dentin (18.19 +/- 2.29 MPa). The
      only exception from these findings in the present study was All-Bond 2.
      Regardless of the provisional materials used, the bond strength values of All
      Bond 2 remained low (maximum SBS with Fermit as intermediate provisional cement:
      4.63 +/- 2.91 MPa).

PMID- 9002802
TI  - Shear bond strength, microleakage and antimicrobial properties of AElitebond.
AB  - PURPOSE: To evaluate the shear bond strength (SBS) and microleakage (ML) to
      dentin as well as the antimicrobial action against five strains of oral bacteria
      of AElitebond single primer restorative system. MATERIALS AND METHODS: Fifteen
      molars were tested to failure for each of the four time periods: 15 minutes, 24
      hours, 7 days and 30 days, after final cure. The test specimens were prepared on
      the dentin surfaces of the extracted molars ground on 600 grit SiC paper. The
      bonded cylinders were removed from the assembly apparatus after cure, stored in
      physiological saline at 37 degrees C for the four different time periods and
      subjected to a shear bond load at 0.5 mm/minute until fractured. For the
      microleakage determination, Class V cavity preparations were done on the facial
      surfaces of the roots of 15 canines below the cemento-enamel junction and the
      specimens thermocycled (500x) between 8 degrees C and 15 degrees C in 2%
      methylene blue. The teeth were cut into 6 mm thick sections and the sections
      which included the restorations were separately dissolved in acid. The color
      intensities of the dissolved sections were measured at a wavelength of 590 nm
      against a standard curve which was constructed from the dye. The modified model
      cavity method of Meryon & Johnson (1989) was used to assess the antimicrobial
      properties of the restorative system. RESULTS: The mean SBS values (in MPa) were
      found to be 10.3, 9.8, 11.47 and 9.9 after 15 minutes, 24 hours, 7 days, and 30
      days, respectively. There was no significant increase (P < 5%) in the SBS after
      15 minutes. The ML of 0.76 micrograms dye/ restoration was relatively low in
      comparison to the SBS values. The restorative system significantly (P < 5%)
      inhibited the growth of Actinomyces naeslundii with 88%, Streptococcus mutans
      with 42%, Streptococcus sanguis with 39% and Streptococcus oralis with 9%.
      However, the growth of Veillonella parvula was stimulated with 49%.

PMID- 9002803
TI  - Pulpal response to dentin etched with 10% phosphoric acid.
AB  - PURPOSE: To histopathologically evaluate the effect of etching sound dentin with
      10% phosphoric acid, in cavities prepared just within the DEJ on young patients.
      MATERIALS AND METHODS: Twenty-four orthodontic patients who required premolar
      extractions were selected for the study. Each of the patients had facial Class V
      resin composite restorations placed in two maxillary premolars selected for
      extraction. Each preparation was cut circular, 2 mm in circumference and 0.5 mm
      into dentin. The dentin of one maxillary premolar preparation, randomly selected,
      was etched with 10% phosphoric acid (Bisco) for 20 seconds. This was followed by
      the placement of a dentin bonding agent (All-Bond 2) and a microfilled composite
      restoration (Silux). The contralateral maxillary premolar, received a similar
      preparation, but the dentin surface was lined with a light-cured glass ionomer
      liner before etching of the enamel, followed by placement of a dentin bonding
      agent and a microfilled resin composite restoration. One of the mandibular
      premolars was randomly selected as a negative control, having no treatment.
      Fourteen days after the placement of the restorations, the teeth were extracted,
      and histologically examined for insult to the pulpal tissues. Injury to the pulp
      was evaluated by quantitative measures of histopathology, including necrosis,
      infiltration by inflammatory cells, and other indicators of tissue injury.
      RESULTS: Using a Kruskal-Wallis analysis, there was no statistically significant
      difference in pulpal histopathology of the teeth with etched dentin versus teeth
      with dentin protected by a liner or the negative control teeth (P < 0.05).

PMID- 9002804
TI  - Dentastic bond strength to dentin.
AB  - PURPOSE: To evaluate the shear bond strength to the dentin of permanent teeth and
      failure site of Dentastic hydrophilic dentin bonding agent. MATERIALS AND
      METHODS: Forty permanent noncarious molar teeth stored in distilled water were
      obtained. The teeth were cleaned with pumice and a rubber cup. The mesio-buccal
      surface of the teeth was ground flat with hand pressure with a series of SiC
      paper ending with the 600 grit to provide a uniform surface on dentin to which
      the resin composite could be applied. After preparing the tooth surface, the
      teeth were stored in distilled water for 48 hours. They were then divided at
      random into four groups of 10 specimens each: Group 1: Dentastic, five coats of
      primer; Group 2: Dentastic, three coats of primer; Group 3: Dentastic, five coats
      of primer, light-cured adhesive before resin bonding; Group 4: Dentastic, three
      coats of primer, light-cured adhesive before resin bonding. All specimens were
      thermocycled (500x) and sheared in a testing machine. After shear testing, the
      debonded sites of all samples were examined with a stereomicroscope and a
      scanning electron microscope. RESULTS: The results in MPa were: Group 1: 22.63 +/
      6.24; Group 2: 23.35 +/- 5.14; Group 3: 23.58 +/- 5.66; Group 4: 27.26 +/- 8.22.
      ANOVA and Student-Newman-Keuls showed no statistically significant difference
      between the groups. In all groups, all specimens failed at the dentin (dentin
      cohesive failure = dentin fracture) or at the resin (resin cohesive failure =
      resin fracture). This means that the bond strength of the product is stronger
      than the cohesive strengths of the dentin and the resin.

PMID- 9002805
TI  - Effect of a surface sealant on microleakage of Class V restorations.
AB  - PURPOSE: To evaluate the effect of a low-viscosity surface-penetrating sealant on
      microleakage around Class V restorations. MATERIALS AND METHODS: Box-shaped Class
      V preparations were made in the facial and lingual surfaces of 50 extracted human
      teeth. Occlusal margins were in enamel and gingival margins were in
      dentin/cementum. Preparations were restored with the following systems (n = 20):
      Dentin Conditioner + Fuji II LC; ProBond primer + VariGlass VLC; OptiBond + XRV
      Herculite; Scotchbond Multi-Purpose + Silux Plus; and Scotchbond Multi-Purpose +
      Restorative Z100. Half of the restorations in each group were randomly selected
      and sealed with Fortify resin immediately after finishing and polishing.
      Specimens were thermocycled 500x between 5 degrees and 55 degrees C and subjected
      to a silver nitrate microleakage test. Penetration of the silver nitrate tracer
      was evaluated and recorded using a 0-4 ordinal scale. Data were analyzed using
      non-parametric statistical tests. RESULTS: All of the restorative systems had
      very little leakage at enamel margins, regardless of whether the resin sealant
      was used. Each of the systems except VariGlass had minimal leakage at unsealed
      dentin margins also. Application of the resin sealant significantly reduced
      leakage at the interface between VariGlass and dentin or cementum, but had no
      effect on the other restorative systems.

PMID- 9002806
TI  - Pain elicited during intraoral infiltration with buffered lidocaine.
AB  - PURPOSE: To evaluate the effect of buffered lidocaine with self reporting of pain
      elicited during maxillary labial and palatal infiltrations of permanent canines.
      MATERIALS AND METHODS: A standardized, prospective clinical trial of adult
      volunteers using a cross-over design of 20 paired injections using conventional
      2% lidocaine with 1:100,000 epinephrine as the control. RESULTS: Failed to
      establish a significant reduction in pain scores for either injection site when
      buffered lidocaine was injected intraorally.

PMID- 9002807
TI  - Effect of disinfectants on the bond strength of composite to dentin.
AB  - PURPOSE: To investigate the effect of two cavity disinfectants, a 2%
      chlorhexidine (Bisco) and a 0.11% iodine/potassium-iodide/copper sulfate solution
      (ORA-5), on the shear bond strength of composite to dentin mediated by the dentin
      bonding agents (DBA), Syntac and Tenure. MATERIALS AND METHODS: The occlusal
      surfaces of 72 noncarious extracted human molar teeth were flattened to dentin
      using 500 grit sandpaper. They were randomly assigned (n = 12) to three groups
      within each DBA system: Bisco/Tenure, ORA-5/Tenure, Tenure, Bisco/Syntac, ORA
      5/Syntac and Syntac. Dentin disinfectants were applied for 20 seconds and dried.
      DBA was applied following manufacturer's instructions. A hybrid resin composite
      (Tetric) was then bonded to all treated samples. The samples were thermocycled
      and tested in shear until failure. Fracture analysis was performed on dentin
      surfaces with both light and scanning electron microscopy. Shear bond strength
      data was analyzed using ANOVA, Student-Neuman-Keuls and Dunnett tests at P <
      0.05. RESULTS: Shear bond values (Mean +/- SD, MPa) were: Syntac control 14.3 +/-
      2.0, Bisco/Syntac 8.1 +/- 4.9 and ORA-5/Syntac 5.7 +/- 5.1; Tenure control 15.0
      +/- 1.9, Bisco/Tenure 14.2 +/- 3.0 and ORA-5/Tenure 13.9 +/- 3.7. The only
      significant difference found between disinfectant treatment groups and the
      control groups was with Syntac. Fracture surface analysis revealed that with
      Tenure most failures were cohesive in resin but with Syntac, the disinfected
      samples displayed adhesive failures.

PMID- 9002808
TI  - Clinical evaluation of tooth-colored materials in cervical lesions.
AB  - PURPOSE: To determine the 18-month clinical performance of four tooth-colored
      restoratives in non-carious cervical lesions. MATERIALS AND METHODS: Buccal
      abrasion lesions in 83 teeth were restored with each of the following materials:
      Fuji Cap II, Fuji II LC, APH/Universal Bond 3, Lite Fil II A/Imperva Bond.
      Baseline and an 18-month recall was carried out using the Ryge (USPHS) method for
      retention, color match, marginal adaptation, cavosurface marginal discoloration,
      anatomic form and secondary caries. RESULTS: The USPHS results (% alfa) for the
      four products were, respectively: color match (9%, 48%, 57%, 55%), marginal
      discoloration (71%, 76%, 52%, 50%), marginal adaptation (24%, 24%, 33%, 15%),
      anatomic form (67%, 86%, 95%, 45%) and retention (100%, 95%, 100%, 65%). Results
      indicated that (1) Fuji Cap II exhibited a poor color match at baseline (2) Color
      matching of Fuji II LC was comparable to the resin composites and (3) seven Lite
      Fil II/Imperva Bond restorations (35%) were dislodged after 1 1/2 years.

PMID- 9002809
TI  - Effect of thermocycling on the microleakage of conventional and resin-modified
      glass ionomers.
AB  - PURPOSE: To compare the effect of thermocycling on the microleakage of
      conventional and resin modified glass ionomer restorative materials. MATERIALS
      AND METHODS: Class V preparations, centered on the CEJ, were prepared on the
      lingual and facial surfaces of 30 extracted human third molar teeth. Preparations
      were conditioned and restored randomly on one surface with Ketac-Fil and on the
      other surface with Photac-Fil. Restorations were protected during curing,
      finishing, and storage with Ketac-Glaze. Specimens were aged in room temperature
      distilled water for 7 days. Half of the specimens were thermocycled for 2,500
      cycles in 5 degrees-55 degrees water baths with 5-second dwell times. All
      specimen apices were sealed with red compound, occlusal fissures sealed with
      pit/fissure sealant, and surfaces painted to within 1.5 mm of restoration margins
      with red nail polish. Specimens were stained with 5% methylene blue, invested in
      orthodontic resin, and sectioned faciolingually. The percentage of dye
      penetration along the tooth restoration interface was measured with a digital
      imaging system. RESULTS: Statistical analysis showed that neither thermocycling
      or type of material had a significant effect on dye penetration (P > 0.5).

PMID- 9002811
TI  - Bond strength of Gluma CPS using the moist dentin bonding technique.
AB  - PURPOSE: To investigate the effects of acetone or water based Gluma primers on
      bonding efficacy when applied to acid-etched wet, dry or rewetted dentin.
      MATERIALS AND METHODS: Shear bond strength (SBS, 24 hours) was measured on human
      dentin etched with 20% phosphoric acid gel and rinsed with water in the wet (blot
      dried), the conventional (2 seconds air blast), the dry (10 seconds air drying),
      and the rewetted stage (10 seconds air drying, remoistening and blot drying). The
      priming solution was either the original water based or an acetone based
      experimental Gluma primer. Cavity sealing performance and depth of resin
      impregnation were determined by solvent and by technique along the margins of 4.5
      mm wide cylindrical dentin cavities with 90 degree cavosurface angle. RESULTS:
      The SBSs of the wet technique groups were approximately 18 MPa, irrespective of
      the primer solvent. Conventional drying gave an SBS almost as high (16.5 MPa).
      Rewetting was highly effective with acetone as the primer solvent. The dry
      techniques resulted in moderate (water) and poor (acetone) bond strengths. The
      cavity margins of acetone based primer treated specimens were consistently gap
      free with the wet technique. The other seven groups showed between two and six
      gaps in each group of six specimens. The resin impregnated layer (RIL)
      thicknesses were 12.5 microns approximately in the wet groups, and thus identical
      with the total depth of demineralization resulting from the 30-second etching.
      The alternative techniques showed significantly thinner RILs particularly in the
      dry groups (7.5 microns).

PMID- 9002810
TI  - 3-year clinical evaluation of modified Gluma adhesive systems in cervical
      abrasion/erosion lesions.
AB  - PURPOSE: To study the clinical performance of two candidates for improvement of
      the original Gluma bonding system. MATERIALS AND METHODS: Eight teeth with
      cervical buccal abrasion/erosion lesions were identified in 40 patients. The
      lesions were conditioned with an oxalic acid solution followed by either a HEMA
      glutaraldehyde bonding agent or a formamide-containing bonding agent. The lesions
      were restored with a hybrid composite. Each patient received the same number of
      restorations with the two different bonding formulations. All restorations were
      made by the same operator (JK). Evaluations were based on the USPHS system.
      RESULTS: No difference between the two groups as to retention, marginal
      adaptation and discoloration was observed after 3 years. Eight restorations were
      lost and a slight increase in marginal discoloration was seen during the
      observation period.

PMID- 9002812
TI  - Bond strength of composite to sound and artificial carious dentin.
AB  - PURPOSE: To determine the in vitro bond strength of a composite (Herculite XRV)
      to sound dentin and artificial carious lesions in dentin. MATERIALS AND METHODS:
      Buccal and lingual surfaces from extracted human molar teeth were ground to
      expose sound dentin surfaces. The buccal surface was maintained as sound dentin,
      while an artificial carious lesion was created in the lingual surface using an
      acidified gelatin gel. A bonding agent (Optibond) was applied to both buccal and
      lingual surfaces with and without prior etching with 37.5% phosphoric acid. The
      composite was applied and debonded under tension after 24 hours in water at 37
      degrees C. RESULTS: Both sound dentin (23.1 MPa) and etched sound dentin (22.2
      MPa) had similar bond strengths, whereas artificial carious lesions in dentin
      that had been etched (11.8 MPa) and non-etched dentin lesions (8.8 MPa) had
      significantly lower bond strengths. Adhesive failures were greatest for dentin
      lesions (60-95%) and least for sound dentin(40-50%). Etching with phosphoric acid
      did not improve the bond strength of composite to sound dentin or artificial
      carious lesions in dentin.

PMID- 9002814
TI  - Microleakage of CAD-CAM porcelain restorations.
AB  - PURPOSE: To evaluate the microleakage of CAD-CAM porcelain inlay restorations
      cemented with four different dual cure resin cements. MATERIALS AND METHODS:
      Thirty human extracted caries-free molar teeth were prepared with a Class II MOD
      cavity design. One proximal box ended on enamel and the other on root surface
      dentin. The teeth were divided into six groups of five samples each. Two groups
      were restored with a direct placement composite resin to serve as a control. The
      other four groups were restored with CAD/CAM-generated ceramic inlays that were
      cemented with four dual cure resin cements. All specimens were thermocycled.
      Microleakage of the restorations was assessed by dye penetration. RESULTS:
      Compared to direct placement resin composite which demonstrated an excellent
      enamel marginal seal, CAD/CAM-generated porcelain inlays produced excellent
      marginal seals at both the enamel and dentin interfaces.

PMID- 9002813
TI  - Microleakage of bonding agents with wet and dry bonding techniques.
AB  - PURPOSE: To assess the microleakage of Class V preparations restored with three
      bonding agents using wet and dry bonding. MATERIALS AND METHODS: Cavities were
      prepared in the buccal and lingual surfaces of extracted human premolar teeth and
      restored with resin composite after application of the dentin bonding agents,
      using a wet or dry bonding technique. The teeth were stored for 2 weeks at 37
      degrees C, thermocycled, and the restorations examined for leakage using buffered
      methylene blue as the marker. The teeth were sectioned bucco-lingually through
      the restorations and the degree of microleakage assessed microscopically.
      RESULTS: All groups showed leakage at both the dentin and enamel margins. There
      was no significant difference in leakage at the enamel margins between groups (p
      > 0.05) and no significant differences in leakage between the wet bonding (P >
      0.05) or dry bonding (P > 0.05) procedures. However, when comparing the effects
      of wet and dry bonding, there was less leakage at the gingival margin in the
      groups where the bonding agent was acetone-based and wet bonding was used (P <
      0.03). There was no significant difference in leakage for Scotchbond Multi
      Purpose Plus when either maleic acid or phosphoric acid was used as the etchant
      (P > 0.05).

PMID- 9002816
TI  - The overwet phenomenon: an optical, micromorphological study of surface moisture
      in the acid-conditioned, resin-dentin interface.
AB  - PURPOSE: To evaluate the morphological effect of different degrees of surface
      wetness on "wet bonding" upon the acid-conditioned, resin-dentin interface using
      an acetone-containing adhesive system (All-Bond 2). MATERIALS AND METHODS: Dentin
      surfaces were conditioned with 10% phosphoric acid (20 seconds), washed and air
      dried (3 seconds) or blot dried. RESULTS: The surfaces were characterized by the
      formation of an intact layer of resin impregnated dentin. Dentin tubules were
      sealed with solid cores of primers commonly below which were intratubular primer
      globules. Excess moisture on the dentin surface resulted in the creation of
      blister-like spaces at the primer-dentin interface. A layer of resin-impregnated
      intertubular dentin was present and below such spaces were incompletely sealed
      tubules. Primer globules were also observed on the dentin surface. The presence
      of microscopic voids at the primer-dentin interface may offer a morphological
      explanation for the published decrease in bond strength when this system was
      applied in the presence of excessive surface moisture.

PMID- 9002815
TI  - Glove contamination of etched porcelain surfaces and bond strength to enamel.
AB  - PURPOSE: To investigate whether contamination of etched porcelain surfaces by
      operating gloves of different types alters the shear bond strength of the
      porcelain to a resin-composite luting material. MATERIALS AND METHODS: Fifty
      porcelain specimens of 7 mm diameter and 2 mm thick were manufactured in
      feldspathic porcelain. After randomly dividing the specimens into five groups of
      10 specimens, the porcelain surface of each specimen was etched with hydrofluoric
      acid. Samples of glove material, taken from the outer surface of gloves typically
      used in clinical dentistry, were held against the etched porcelain surface for 10
      seconds. Four different glove types were used, Group 1: Biogel D; Group 2:
      Featherlite; Group 3: Microtouch; and Group 4: Tru-Touch; Group 5: Control/not
      treated with glove material. A resin composite-based luting material of standard
      shade was placed against the treated porcelain surface in a PTFE mold of 2 mm
      diameter and 2 mm depth, and light-cured from a direction of 90 degrees to the
      porcelain surface for 60 seconds. Each specimen was tested in shear, the results
      noted and subjected to statistical analysis. RESULTS: The mean shear bond
      strengths (MPa) for Groups 1, 2, 3 and 4 were 22, 21, 16 and 23 and for the
      control group, 26. Statistical analysis of the results indicated that there was
      no significant difference between the groups.

PMID- 9002817
TI  - Histological characteristics of peri-implant mucosa around Branemark and single
      crystal sapphire implants.
AB  - Soft tissues surrounding Branemark titanium implants and single crystal sapphire
      implants were studied by conventional light- and transmission electron microscopy
      and by immunohistochemical markers for cytokeratin, protein S-100, Factor VIII
      and KP1. Histological sections of biopsies obtained from clinically healthy peri
      implant mucosa were separated into a keratinized outer implant epithelium and an
      inner, non-keratinized epithelium, both immunoreactive towards cytokeratin. The
      inner implant epithelium terminated in a junctional epithelium, apically not a
      few cell layers thick. The cells adjacent to the implant showed a condensed
      cytoplasm, resembling hemidesmosomes. In the underlying connective tissue, rich
      in fibroblasts and factor VIII immunoreactive blood vessels, the bundles of
      collagen ran in different directions. S-100 immunoreactive nerve structures were
      more frequently found beneath the outer than the inner implant epithelium.
      Inflammatory cell infiltrates, some KP1 positive, were observed in the apical
      parts of the inner implant epithelium. S-100 positive Langerhans' cells were
      present mainly within the the outer implant epithelium. For the two implant
      systems, the techniques disclosed no qualitative structural differences in the
      adjacent soft tissues.

PMID- 9002818
TI  - Comparison of healed tissues adjacent to submerged and non-submerged unloaded
      titanium dental implants. A histometric study in beagle dogs.
AB  - This study involved histometry of the healed tissues around submerged and
      nonsubmerged dental implants in beagle dogs. In a split-mouth design, 19
      submerged and 19 nonsubmerged commercially pure titanium implants, titanium
      plasma-sprayed in the bone anchoring part and smooth in the transmucosal portion,
      were placed in the mandibles of 6 dogs. Oral hygiene was performed 3 times
      weekly. After 3 months of healing, transmucosal abutments were inserted in the
      submerged implants. Six weeks after second stage surgery, the dogs were
      sacrificed and specimens obtained and processed for histology and histometry.
      Using a light microscope and a digitizing pad, the distance from implant top to
      mucosa border (DIM), the extent of epithelial downgrowth (ED), the attachment
      level, (AL), the length of connective tissue contact (CTC) and the distance of
      the first coronal alveolar bone contact from the implant top (DIB) were measured
      at the mesial and distal aspects. Means +/- standard deviations for submerged and
      nonsubmerged implants were calculated, with the dog being the unit of measure. No
      statistically significant differences between submerged and nonsubmerged implants
      were found for DIM, CTC and DIB. However, significant differences were observed
      for ED and AL. This study in beagle dogs indicates that the apical extension of
      the peri-implant epithelium is significantly greater and the attachment level
      significantly lower adjacent to submerged implants with second-stage transmucosal
      abutments than in nonsubmerged, one-stage implants.

PMID- 9002819
TI  - Radiographical and histological characteristics of submerged and nonsubmerged
      titanium implants. An experimental study in the Labrador dog.
AB  - Using 5 Labrador dogs, certain characteristics of the peri-implant tissues were
      analyzed after a 1-step surgical procedure for installation of Branemark
      implants. Six titanium implants, in each mandibular quadrant, were installed in
      the regions of the right and left first molars and the fourth and third
      premolars. In the right mandibular quadrant, a traditional 2-step procedure was
      employed, whilst in the left quadrant, a 1-step procedure was carried out. The
      animals were monitored during a 6-month period. Biopsies of the healed peri
      implant mucosa showed signs of superficial inflammation. The histological
      analysis revealed that i) the connective tissue lateral to the junctional
      epithelium showed limited accumulations of inflammatory cells (PICT), and ii)
      that at implant sites that had been exposed to the oral cavity for 6 months (1
      step implants), an inflammatory cell infiltrate (abutment ICT) consistently was
      present in the tissues facing the abutment-fixture junction (AFJ). This
      infiltrate was separated from the bone crest by a 0.8-mm-wide zone of normal
      connective tissue. Irrespective of the surgical procedure applied, the
      radiographic and histometric measurements disclosed that i) the crestal bone loss
      was about 2.4 mm, ii) the height of the peri-implant mucosa varied from 3.5 mm to
      3.9 mm, iii) the bone crest was located 1.1-1.5 mm apical of AFJ as well as of
      the apical termination of the junctional epithelium (aJE), and iv) a junctional
      epithelium of 2.1-2.4 mm faced the implant surface. In conclusion, this study
      demonstrates that, using a dog model, titanium dental implants ad modum Branemark
      installed according to a 1-step or to a 2-step surgical procedure will obtain
      similar soft tissue adaptation and proper bone anchorage (osseointegration).
      Further studies are, however, required to ascertain the long-term clinical
      feasibility of the 1-step approach.

PMID- 9002820
TI  - Proliferation, differentiation, and protein synthesis of human osteoblast-like
      cells (MG63) cultured on previously used titanium surfaces.
AB  - This study compared osteoblasts proliferation, differentiation, and protein
      synthesis on new and used titanium (Ti) disks to test the hypothesis that
      cleaning and resterilization of previously used Ti disks does not alter cell
      response to a particular surface. Ti disks of varying roughness were prepared by
      one of five different treatment regimens. Standard tissue culture plastic was
      used as a control. Human osteoblast-like cells (MG63) were cultured on the Ti
      disks and cell proliferation, cell differentiation, RNA synthesis and matrix
      production (collagen and noncollagen protein; proteoglycans) measured. After
      their first use, the disks were cleaned, resterilized by autoclaving, and MG63
      cells cultured on them as before. At confluence, the same parameters were
      measured and cell behavior on new and used disks compared. When confluent
      cultures of cells on plastic were compared to those cultured on new Ti surfaces,
      cell number was reduced on the roughest surfaces and equivalent to plastic on the
      other surfaces. Cell number was further reduced when disks with the roughest
      surfaces were re-used; no differences in cell number could be discerned after
      cleaning and resterilization. Cell proliferation was inversely related to surface
      roughness and was less than seen on tissue culture plastic. Re-use of the Ti
      disks resulted in no change in cell proliferation rate. Alkaline phosphatase
      specific activity in isolated cells was lowest on the rougher surfaces; no
      differences between new and used disks were observed. Similarly, enzyme activity
      in the cell layer was decreased in cultures grown on rougher surfaces, with no
      effect of prior disk use being noted. RNA synthesis was decreased with respect to
      plastic in cultures on smoother surfaces and increased on rougher surfaces; prior
      disk use did not alter RNA synthesis. Collagen production by the cells was
      decreased on smoother surfaces, but was comparable to tissue culture plastic when
      grown on rougher surfaces. Non-collagen protein production was unaffected by
      culture surface and whether or not the disk had been previously used.
      Proteoglycan synthesis by cells was decreased on all surfaces studied and
      comparable on both new and used disks. The results of this study indicate that Ti
      implant surfaces are unaffected by cleaning and resterilization, although rougher
      surfaces may require more extensive cleaning than smoother ones. This suggests
      the possibility that implants, in the same patient, could be safely reused. In
      vivo studies in animals, however, need to be performed before clinical
      application can be considered.

PMID- 9002821
TI  - A novel model system for the study of experimental guided bone formation in
      humans.
AB  - The aim of the present experiment was to test a novel model system, designed to
      obtain human specimens of regenerated and also newly regenerated jaw bone, for
      the study of the biological events under a variety of conditions. Following
      information and disclosure of possible risks associated with a minor oral
      surgical procedure, 9 systemically healthy subjects (5 men, 4 women, mean age
      31.7 years) signed consent forms and volunteered to participate in this study.
      Hollow test cylinders with an outer diameter of 3.5 mm, an inner diameter of 2.5
      mm, and 4 mm in height were used. They were manufactured from commercially pure
      titanium and exhibited a highly polished inner surface and a titanium plasma
      sprayed outer rough surface. A mucoperiosteal flap was raised in the retromolar
      area of the mandible corresponding to standard retrained third molar surgery.
      Following flap reflection a standardized hole was drilled through the cortical
      bone into the bone marrow using round burs. The congruent test cylinders were
      firmly placed into the prepared bony bed yielding primary stability. One-and-a
      half to 2 mm of the test device were submerged below the level of the surrounding
      bone, while the remainder surpassed the level of the bone surface. The bone
      facing end of the cylinder was left open, while the coronal soft tissue facing
      end was closed by an ePTFE-membrane. The flap was sutured to obtain primary wound
      closure. In order to prevent infection, penicillin was prescribed systemically
      and oral rinses of chlorhexidine were administered. After 2, 7, and 12 weeks one
      test device including the regenerated tissue was surgically harvested, while
      after 16, 24 and 36 weeks respectively, 2 devices were harvested and processed
      for soft or hard tissue histology or histochemistry. The two surgical procedures
      and the presence of the test cylinders during the time of healing were well
      tolerated by the volunteers. In all 9 subjects generated tissue could
      successfully be harvested. The tissue generated after 2 and 7 weeks presented
      with a cylindrical shape, whereas the specimens harvested at 12 weeks and
      thereafter resembled the form of an hourglass. Specimens of 12 weeks and less
      regeneration time were almost entirely comprised of soft tissue, while specimens
      with regeneration time of 4 months and more were composed of both soft and
      increasing amounts of mineralized tissue. It is concluded that the presented
      model system is suitable to study temporal dynamics and tissue physiology of bone
      regeneration in humans with minimal risk for complications or adverse effects to
      the volunteers.

PMID- 9002822
TI  - Thresholds for tactile sensitivity perceived with dental implants remain
      unchanged during a healing phase of 3 months.
AB  - The aim of the present study was to determine the tactile pressure thresholds
      perceived with dental implants during a three-month healing phase following
      implant placement (osseointegration phase). The absolute threshold of tactile
      perception was measured in a group of patients 1 week, 1, 2 and 3 months
      following implant placement (ITI Dental Implant System, Straumann AG, Waldenburg,
      Switzerland). Contralateral and neighbouring teeth were measured at the same
      time. For determination of the axial forces exerted on the implants and teeth,
      and electronic device with semi-conductor strain gauges was used (Hammerle et al.
      1995). The results demonstrated mean thresholds of tactile perception for the
      implants of 160.2 g (SD 61.7 g, range 77 approximately 283 g) at 1 week, 133.4 g
      (SD 51.9 g, range 32 approximately 239 g) at 1 month, 147.9 g (SD 53.5 g, range
      70 approximately 257 g) at 2 months, and 146.9 g (SD 57.4 g, range 77
      approximately 248 g) at 3 months. Statistical analysis using Student's paired t
      test revealed no significant differences between the values over time. The
      control teeth exhibited mean values for tactile perception of 13.1 g (SD 9.6 g,
      range 5 approximately 47 g) at 1 week, 10.2 g (SD 6.4 g, range 4 approximately 29
      g) at 1 month, 14.8 g (SD 15.9 g, range 2 approximately 58 g) at 2 months, and
      15.4 g (SD 12.2 g, range 3 approximately 36 g) at 3 months. Again, these values
      did not differ significantly from each other and indicated the absence of
      systemic alterations in perceived pressure threshold over the observation period.
      The mean perceived pressure threshold was more than 10 times higher for implants
      than for natural teeth (P < 0.001) at all observation times. It is concluded that
      the absolute threshold of tactile perception with dental implants during the
      phase of osseointegration is not affected by bone and soft tissue healing taking
      place during the time period.

PMID- 9002823
TI  - On the influence of superstructure connection on implant preload: a
      methodological and clinical study.
AB  - In a combined in vitro and in vivo study strain gauges were used to register the
      deformation in two terminal implant abutment cylinders, when connecting three
      different prosthetic appliances. The prosthetic constructions were placed on the
      abutments and fastened in vitro and in vivo by using different torque sequences.
      Furthermore, in the in vitro situation the three medial abutments were replaced
      by abutments which were 100 microns shorter. The results show that even if the
      prosthetic constructions were judged to have a good clinical fit, relatively
      large External Preloads were registered both in vitro and in vivo. No significant
      differences in axial force or in bending movement were found between the torque
      sequences in vivo. There were, however, significant differences in axial force as
      well as in bending moment in the in vitro experiment. When the shorter medial
      abutments were used in vitro, a change in the axial force of approximately 200 N
      was registered. The results confirm that the methodological approach used in this
      study is valid when evaluating preloads.

PMID- 9002824
TI  - Maintenance of implants: an in vitro study of titanium implant surface
      modifications subsequent to the application of different prophylaxis procedures.
AB  - The aim of the present study was to evaluate surface alterations on titanium
      implant necks subsequent to different prophylaxis procedures. Fifty ITI implants
      were utilized. Forty implants were treated with 10 different prophylaxis
      procedures (ultrasonic scaler, plastic tip ultrasonic scaler, stainless steel
      curette, titanium curette, teflon curette, air powered system, abrasive rubber
      cups, polishing rubber cup and brush), and 10 implants were left as untreated
      controls. Surface alterations were studied on an area of 1 mm x 0.9 mm and
      quantified using optical microscopic, SEM and laser prophylometer analysis. The
      use of laser prophylometer provided an objective criterion for evaluation,
      expressing implant neck surface alterations in numeric values in terms of two
      roughness indexes, Ra and Rz. The results showed that, in comparison with the
      controls (Ra = 0.50; Rz = 3.98) the procedures investigated could be divided into
      3 main groups: 1) Methods which altered the implant neck surface producing
      increased roughness (Ra = 0.68-2.08; Rz = 4.68-11.92); 2) Methods which left the
      implant neck surface unaltered (Ra = 0.44-0.57; Rz = 0.42-3.46); 3) Methods
      resulting in a smoothening of the implant neck surface (Ra = 0.36; Rz = 2.15).
      Group 1 included procedures that should be avoided. However, it appeared safe to
      apply the procedures of groups 2 and 3. To confirm these results, it will be
      necessary to evaluate the plaque- and calculus-removing efficacy from titanium
      neck implant surfaces in vivo.

PMID- 9002825
TI  - Retrospective multicenter analysis of 3i endosseous dental implants placed over a
      five-year period.
AB  - Osseointegrated dental implants have now become an accepted form of treatment for
      patients with a fully or partially missing dentition. The purpose of this study
      was to evaluate the performance of 3i threaded and cylindrical implants. During a
      5-year period, a total of 1969 3i endosseous implants were placed at 6 centers in
      the United States and 2 elsewhere in the edentulous and partially edentulous jaws
      of 653 consecutive patients ranging in age from 18 to 82 years. Of the total
      number of implants placed, 1341 were commercially pure titanium threaded implants
      and 628 were titanium plasma-sprayed implants with a cylindrical configuration. A
      total of 28 patients with 110 implants were lost to follow-up. Implants in these
      patients were considered neither a success nor a failure. Success was predicated
      on the osseointegration of each and every implant followed in this analysis
      rather than the persistence of prosthetic function. Confirmed bone anchorage was
      considered essential for success. A total of 625 patients with 1871 implants
      remain in the study with a follow-up period ranging from 6 to 60 months. A total
      of 93 implants (5.0% of the total implants followed) were considered as failures.
      A mean implant survival rate was 95.0% for both the threaded and the cylindrical
      implant was calculated. The success rate of threaded implants was 97.0% in the
      mandible and 93.8% in the maxilla. The success rate for the 3.3-mm cylindrical
      implants was 96.0% in the mandible and 95.5% in the maxilla, and the success rate
      of 4.0-mm-diameter cylindrical implants was 95% in the mandible and 92.0% in the
      maxilla. Causes of failure consisted of loss of osseointegration (2.3%), crestal
      bone loss requiring periodontal therapy after the first year of function (1.7%)
      had mechanical problems associated with the prosthesis (0.9%). This retrospective
      analysis of the 3i endosseous implant system is comparable to previous reports on
      other implant systems in terms of implant survival and prosthesis stability. It
      is demonstrated that 3i implants are predictable and can provide lasting
      osseointegration leading to improvement of oral function if the recommended
      surgical and restorative protocol is followed.

PMID- 9002826
TI  - Bacterial colonization on internal surfaces of Branemark system implant
      components.
AB  - The aim of the present study was to examine the microbiota on the internal
      surface of the components of 28 Branemark implants in 10 partially edentulous
      patients who had been treated with 1 fixed partial prostheses each. The
      prostheses had been in function for 1 to 8 years. The fixed prostheses were
      checked for mobility and removed. The abutment screws were loosened and
      classified as stable, easily removed or loose. Then, bacterial samples were
      obtained from the various internal surfaces of the implant system. Estimation and
      identification of the most predominant species was performed on the blood agar
      plates. Identification was based on Gram reaction, oxygen sensitivity and
      biochemical tests. Internal surfaces of different components of the Branemark
      implants, after varying periods of function in the oral cavity, consistently
      harboured a heterogeneous and primarily anaerobic microbiota. The individual
      samples showed a great variation. No relation could be seen between type and
      length of abutment, abutment stability, bone loss and type and number of
      microorganisms found in the samples. The flora consisted mainly of facultative
      and anaerobic streptococci, Gram-positive anaerobic rods such as
      Propionibacterium, Eubacterium and Actinomyces species and Gram-negative
      anaerobic rods including Fusobacterium, Prevotella and Porphyromonas species.
      There are reasons to suggest that this presence of bacteria is the result of (i)
      a contamination of the fixture and abutment components during the 1st and/or 2nd
      stage of implant installation and/or (ii) a transmission of microorganisms from
      the oral environment during function subsequent to bridge installation.

PMID- 9002827
TI  - The biocompatibility (cell culture and histologic study) of hydroxy-apatite
      coated implants created by ion beam dynamic mixing.
AB  - Titanium implants were coated with hydroxyapatite by using a method of ion beam
      dynamic mixing. Coated and noncoated plates of titanium were placed in a growth
      medium with fibroblast cells. Implant screws, coated and noncoated, were inserted
      in rabbit bones and the animals were euthanized after 7, 27, and 122 days,
      respectively. The results from the cell culture test showed no visible difference
      between the specimens. Histologic examination of implant specimens indicated more
      new bone activity against coated screws at 27 days, and that was more pronounced
      at 127 days. Although the amount of new bone formation was not significantly
      different, certain signs of favourable new bone formation could be seen in
      contact with coated implants compared to the noncoated controls.

PMID- 9002828
TI  - Initial healing in the dog of submerged versus non-submerged porous-coated
      endosseous dental implants.
AB  - It has previously been reported that porous-coated root form endosseous dental
      implants, became well integrated when used in the traditional 2-stage surgical
      approach. In this study, the placement of the implant in a 1-stage (non
      submerged) technique was to be explored. Implants were placed in the mandibles of
      dogs, and 2 designs were used differing only in that one (experimental) had a 3
      mm transgingival extension, permitting it to be exposed to the oral cavity from
      the outset. 12 (3 per animal) non-submerged implants were placed on 1 side of 4
      beagle dogs and 12 control (submerged) implants were placed contralaterally. All
      implants were allowed to heal for 6 weeks, after which histological preparations
      were made. 2 of 12 non-submerged implants were lost due to post-operative
      complications; otherwise, all implants healed uneventfully. Histomorphometric
      analysis revealed bone-implant contact, as assessed by absolute bone contact
      (ABC) and contact length fraction (CLF), to be greater for the submerged design,
      suggesting that bone healing may be delayed with the non-submerged approach. As
      well, at this early stage of healing, for both implant designs, ABC and CLF were
      significantly greater on proximal than on buccal and lingual aspects.

PMID- 9002829
TI  - The effect of subcrestal placement of the polished surface of ITI implants on
      marginal soft and hard tissues.
AB  - In order to achieve esthetically more satisfying results, it has been proposed to
      place ITI implants with their border between the rough and smooth surfaces below
      the level of the alveolar crest, thereby obtaining a submucosally located implant
      shoulder following healing. The aim of the present experimental study was to
      clinically and radiographically evaluate the tissue response to the placement of
      one-stage transmucosal implants with the border between the rough and the smooth
      surfaces sunk by 1 mm into a subcrestal location. 11 patients underwent
      comprehensive dental care including the placement of 2 implants of the ITI Dental
      Implant System in the same quadrant (test and control). Randomly assigned control
      implants were placed according to the manufacturer's instructions, i.e. the
      border between the rough titanium plasma-sprayed and the smooth polished surfaces
      precisely at the alveolar crest. At the test implant the apical border of the
      polished surface was placed approximately 1 mm below the alveolar crest. Probing
      bone levels were assessed at implant placement (baseline), 4 and 12 months later.
      Modified plaque and modified gingival indices were recorded at 1, 2, 3, 4 and 12
      months. Clinical probing depth and "attachment" levels were measured at 4 and 12
      months. All parameters were assessed at 6 sites around each implant. The mean for
      each implant was calculated and used for analysis. The Wilcoxon matched pairs
      signed rank test and the Student t-test were applied to detect differences over
      time and between the test and control implants. At baseline, a mean difference in
      probing bone level of -0.86 mm (SD 0.43 mm, p < 0.05) was found between test and
      control implants with the test implants being placed more deeply. Both test and
      control implants lost a significant amount of clinical bone height during the
      first 4 months (test 1.16 mm, p < 0.05; control 0.58 mm, p < 0.05). However, only
      the test implants significantly lost clinical bone height from 4-12 months (test
      1.04 mm, p < 0.05; control 0.45 mm, p = 0.08). Overall, the test implants lost
      2.26 mm and the control implants 1.02 mm of bone height during the first year of
      service. On the average, the test implants demonstrated a bone level of 0.38 mm
      lower than the controls at 12 months. Except for the modified gingival index at 4
      months (mean difference 0.21, SD 0.19, p < 0.05), no clinical parameters yielded
      significant differences between test and control implants at any time. It is
      concluded that in addition to the crestal bone resorption occurring at implants
      placed under standard conditions, the bone adjacent to the polished surface of
      more deeply placed ITI implants is also lost over time. From a biological point
      of view, the placement of the border between the rough and the smooth surfaces
      into a subcrestal location should not be recommended.

PMID- 9002830
TI  - Influence of initial implant mobility on the integration of titanium implants. An
      experimental study in rabbits.
AB  - In the present study, the influence of initial instability on the healing of
      titanium implants was studied in 9 lop-eared rabbits. Titanium implants
      (Branemark System) were inserted in the tibiae, a location with cortical bone
      only, in such a way that they were either stable (control), rotation-mobile, or
      totally mobile. Implants were also inserted in the distal femoral condyles,
      representing an implantation bed with mainly cancellous bone, so they either
      showed no initial mobility (control) or were rotation-mobile. After 12 weeks of
      healing, the implants were retrieved, together with surrounding bone, fixed,
      dehydrated, and embedded in plastic resin. About 10 micron thick ground sections
      were prepared for light microscopic morphometry. The mineralized bone to titanium
      contact, and the amount of bone occupying the threads, were calculated,
      whereafter the outcome of the different locations were compared. All retrieved
      implants were clinically stable at the of the experiment. For the tibia sites, a
      statistically significant less bone to titanium contact, and a less amount of
      bone in the threads, were found for the totally mobile implants, as compared to
      the corresponding initially stable controls. Moreover, a statistically
      significant higher amount of bone was found in the threads of the rotation-mobile
      implants inserted in the femoral condyle as compared to their initially stable
      controls. The study indicated that initial rotation-mobility, independent if it
      occurs in cortical or trabecular bone, does not necessarily lead to an inferior
      integration of unloaded implants. However, initial total implant mobility within
      the cortical layer results in a statistically significant less amount of bone
      around the implants, as compared to stable controls.

PMID- 9002831
TI  - Influence of soft tissue contamination on the integration of titanium implants.
      An experimental study in rabbits.
AB  - In the present study, the influence of peroperative soft tissue contamination on
      the healing of titanium implants was studied in 9 lop-eared rabbits. Titanium
      implants (Branemark System) were inserted in the tibiae, a location with cortical
      bone only, in such a way that one group was inserted the standard way (control),
      and another group was contaminated for 30 s in the adjacent soft tissues, prior
      to insertion. The implants were allowed to heal for 12 weeks and were then
      retrieved together with surrounding bone, fixed, dehydrated and embedded in
      plastic resin. About 10 micron thick ground sections were prepared for light
      microscopic morphometry. The mineralized bone-to-titanium contact, and the amount
      of bone occupying the threads, were calculated for each implant, and the results
      of the two groups were compared. All retrieved implants were clinically stable at
      the end of the experiment. Regarding bone-to-titanium contact and bone area
      within the threads, a statistically nonsignificant difference was observed
      between the 2 groups. This study indicated that peroperative soft tissue
      contamination of c.p. titanium implants does not prevent osseointegration from
      occurring, when studied in the rabbit tibia.

PMID- 9002832
TI  - Progressive peri-implantitis. Incidence and prediction of peri-implant attachment
      loss.
AB  - The aim of this prospective study was to characterize an implant patient
      population exhibiting clinical signs of peri-implantitis and to determine
      subsequently the incidence of progressive attachment loss. The predictive values
      of diagnostic parameters were evaluated. 25 patients with 54 endosseous implants
      that had been loaded for 41 +/- 15 months were included in the study. Clinical
      parameters included the assessment of plaque, bleeding on probing, probing depth,
      attachment levels, and Periotest values. Probing measurements were performed in
      duplicate by means of a controlled force electronic probe (Periprobe). Peri
      implant crevicular fluid samples were collected and assayed for neutral
      proteolytic enzyme (NPE) activity (Periocheck). Analysis of duplicate baseline
      probing data revealed a high degree of reproducibility (mean difference: 0.1 +/-
      0.3 mm). A minimum threshold of 1.0 mm (> 3 x S.D.) loss of probing attachment
      was chosen to classify a site as positive for breakdown. Alternatively, the
      tolerance method was employed to identify sites with progressive attachment loss.
      After 6 months, irrespective of the analytical method, 6 percent of all sites (in
      19% of the implants) and 28% of the patients had experienced further peri-implant
      attachment loss. There were significant differences (p < 0.05) in mean plaque
      (73% vs. 45%) and NPE (36% vs. 12%) scores between patients with progressive peri
      implantitis and those with stable peri-implant conditions. Both bleeding on
      probing and the NPE-test were characterized by high negative predictive values,
      and thus negative scores can serve as indicators for stable peri-implant
      conditions. For monitoring peri-implant health during recall visits, attachment
      level recordings with a controlled force electronic probe in conjunction with
      enzymatic diagnostic tests of the host response can be recommended.

PMID- 9002833
TI  - Loss of osseointegration caused by occlusal load of oral implants. A clinical and
      radiographic study in monkeys.
AB  - The breakdown of bone around oral implants following excessive occlusal load or
      plaque accumulation was evaluated in monkeys. 5 screw type implants of pure
      titanium (Astra) were inserted in the mandible of 4 monkeys (Macaca
      Fascicularis). 2 implants were placed in each of the lateral segments and 1 in
      the frontal area. Each monkey was provided with 2 cemented splints covering the
      premolars and molars in the right and left side of the maxilla, respectively. 6
      months after insertion of the fixtures, a fixed partial prosthesis was mounted on
      the 2 implants in one of the lateral segments. The prosthesis was in supra
      occlusal contact with the antagonizing splint. Each prosthesis was replaced
      during the course of the experiment. The renewed prosthesis caused a lateral
      displacement of the mandible during occlusion, and therefore resulted in a
      lateral rather than axial excessive occlusal load. Implants retaining the
      prosthesis were brushed 1 x a week and subgingival cleaning was performed 1 x a
      month. The remaining implants were never cleaned and, additionally, a cotton cord
      was placed passively around each of these to promote plaque accumulation. 5 out
      of 8 implants with excessive occlusal load lost osseointegration (mobility and
      peri-implant radiolucency). The loss of osseointegration was observed 4.5 months
      to 15.5 months after the occlusal overload was commenced. None of the implants
      with plaque accumulation lost osseointegration, although an average loss of 1.8
      mm in the radiographic bone level was assessed after 18 months.

PMID- 9002834
TI  - In vivo measurements of some functional aspects with mandibular fixed prostheses
      supported by implants.
AB  - Maximal occlusal force and oral tactile sensibility were recorded in 21
      edentulous patients wearing maxillary complete dentures and mandibular fixed
      prostheses supported by Branemark implants. Bite force was measured with a
      miniature force transducer between antagonistic molars and premolars, and the
      passive tactile sensibility of the fixtures was recorded in the horizontal and
      vertical directions with spring balances. The active tactile sensibility was
      tested using steel foils (100 to 10 microns). The range of maximal occlusal force
      recorded was from 35 to 330N with highest values observed on the second premolars
      (mean 143N). Significantly lower forces were found on molars and first premolars
      (p < 0.01). The detection threshold of minimal pressure was about 330 g in the
      horizontal, and 388 g in the vertical direction. This difference was not
      statistically significant. The average number of incorrect assessments when
      testing steel foils was 16.6 errors, out of 100 recordings. Similar results when
      using these 3 test modalities had been found on overdentures supported by two
      mandibular implants and occluding with maxillary complete dentures. The results
      of this study suggest that mandibular implants supporting fixed prostheses are
      not likely to improve oral tactile sensibility and maximal occlusal force in the
      presence of maxillary complete dentures.

PMID- 9002835
TI  - Marginal bone levels at Branemark system implants used for single tooth
      restoration. The influence of implant design and anatomical region.
AB  - In this retrospective study of Branemark system oral implants, 75 consecutive
      patients were treated with 84 implants for single-tooth replacement from 1988 to
      1993. Two implants were lost and not replaced: the first one before the abutment
      connection, the latter during the first year in function. The cumulative failure
      rate reached 2.4% during the 5-year period. Seventy-one percent of the implants
      were located in the incisor/canine region of both jaws. Twenty-six per cent of
      the implants were inserted in special presurgical or surgical conditions. The
      mean annual bone loss as scored on radiograph, was 0.8 mm during the first year
      and 0.1 mm the following years. Different implant designs were used, a more
      pronounced bone loss was observed for the conical implant. The present data shows
      that the cumulative failure rate for single Branemark implants and radiographic
      bone loss is similar to that found around implants used for the treatment of
      complete and partial edentulism.

PMID- 9002836
TI  - Non-submerged osseointegrated dental implants with ball attachments supporting
      overdentures in patients with mandibular alveolar ridge atrophy. A short-term
      follow-up.
AB  - Non-submerged, hollow screw ITI-Bonefit dental implants with ball attachments
      supporting overdentures were used as alternative treatment to combined vestibulo
      lingual-plasty with free split-thickness skin graft and removable dentures in 40
      consecutive patients with mandibular alveolar ridge atrophy. One hundred and
      fifty-six non-sub-merged fixtures were installed. Ball attachments were mounted
      on the fixtures and implant-supported overdentures inserted 3-4 months after
      fixture installation. The observation period after implant activation and
      prosthesis insertion varied from 1 to 3 years with a median observation period of
      2 years. The overall success rate of individual implants was 99%(155/156). The
      prosthesis function rate was 100%(40/40). The 1-year success rate of individual
      implants was 99%(155/156) with a prosthesis function rate of 100%(40/40). No
      persistent surgical, periodontic or prosthodontic complications were observed.
      The results indicate that non-submerged osseointegrated ITI-Bonefit dental
      implants with ball attachments supporting overdentures can be a successful
      alternative to combined vestibulo-lingual-plasty with free split-thickness skin
      graft and removable dentures, and as successful as the use of submerged dental
      implants.

PMID- 9002837
TI  - Long-term stability of osseointegrated implants in bone regenerated with the
      membrane technique. 5-year results of a prospective study with 12 implants.
AB  - The purpose of the present clinical study was to evaluate the 5-year results of
      the first 12 implants inserted at the University of Berne in regenerated bone
      following successful ridge augmentation with the membrane technique. The patients
      were recalled and examined with clinical and radiographic parameters routinely
      utilized in prospective studies with standard implants in non-regenerated bone.
      Based on clinical and radiographic findings, all 12 implants were considered
      successfully integrated according to strict criteria of success. The detailed
      analysis of clinical parameters revealed no differences to results of prospective
      studies on standard implants in non-regenerated bone. All implants demonstrated
      ankylotic stability which was confirmed by a mean Periotest value of -2.08. The
      radiographic analysis showed stable bone crest levels with a mean bone loss
      between the 1- and 5-year examination of 0.30 mm. However, 2 implants exhibited a
      bone loss of more than 1 mm between the 1- and 5-year examination. Therefore, the
      prognosis of these 2 implants seems questionable at the present time. It can be
      concluded that bone regenerated with the membrane technique reacts to implant
      placement like non-regenerated bone, since all 12 implants achieved successful
      tissue integration with functional ankylosis. Furthermore, this bone is also load
      bearing, since all 12 implants maintained osseointegration over a 5-year period.

PMID- 9002838
TI  - Evaluation of composite wear with a new multi-mode oral wear simulator.
AB  - OBJECTIVES: The goals of this study were to develop a machine which
      simultaneously produces wear through the two main oral wear mechanisms of
      abrasion and attrition by the action of an enamel antagonist and to compare the
      results obtained for dental composites using this machine to those obtained from
      clinical studies and other in vitro studies. METHODS: The accuracy of this new
      wear tester was determined by examining 11 commercial composite filling materials
      and 1 amalgam. Specimens were subjected to three-body abrasion and attrition wear
      for 50,000 cycles. Profilometry was used to quantitate wear of the composites.
      Linear regression analysis was used to correlate the results to those obtained
      from clinical studies, as well as from other in vitro wear testers. The area of
      enamel wear was also determined by image analysis. The SEM was used to evaluate
      the wear surfaces. RESULTS: The lowest abrasion wear was recorded for the amalgam
      and for the microfill and smaller-particle composites. Attrition wear was
      enhanced for the microfill composites and one small-particle hybrid. There was a
      strong correlation between the results obtained with the new wear tester and
      those obtained in the clinical trials cited in the literature. Wear of the enamel
      antagonist was the greatest for the composites with the largest particle sizes.
      The wear tester showed a reasonable correlation with other wear-producing
      machines. SIGNIFICANCE: A new wear tester developed to evaluate and discriminate
      abrasion and attrition wear provided results similar to those reported in the
      literature for a variety of commercial composites. The new machine is capable of
      characterizing the behavior of a material in multiple wear modes simultaneously
      with one simple, realistic test.

PMID- 9002839
TI  - Antibacterial activity of silver ions implanted in SiO2 filler on oral
      streptococci.
AB  - OBJECTIVE: To evaluate the role of silver ions in composite resin dental
      materials, an in vivo investigation was conducted into the antibacterial effect
      of SiO2 filler implanted with silver ions on oral streptococci. METHODS. SiO2
      filler samples (0.1g) were implanted with silver ions. The effect of the filler
      with silver ions (Ag+ filler) was tested on oral streptococci bacteria. These
      bacterial strains had been isolated predominantly from composite resin surfaces.
      The organisms tested were anaerobically cultured in 5 mL Trypticase Soy Broth
      containing 0.5 per cent yeast extract at 37 degrees C for 10-12 h. Each bacterial
      strain was adjusted to a concentration of 1 x 10(6) cells per mL with reduced
      transport fluid (RTF). Ag+ filler was immersed in 1 mL of RTF and anaerobically
      incubated 2, 6 and 12 h to study the antibacterial effect. The survival of
      bacteria was then estimated by culturing on TSBY agar plates. A plate with
      approximately 100 discrete colonies was chosen from the serial agar cultures, and
      the number of colonies was counted at each sampling time. RESULTS: The Ag+ filler
      showed significantly more antibacterial activity than the control filler without
      silver ions. SIGNIFICANCE: These results indicate that the antibacterial effect
      found in this study was due to the silver ions released by the Ag+ filler and
      that it may be useful to add this filler to composite resin dental materials for
      secondary caries protection.

PMID- 9002840
TI  - Cavity wall adaptation and voids in adhesive Class I resin composite
      restorations.
AB  - OBJECTIVES: Handling characteristics and adaptation modes of resin composites are
      important factors to achieve proper placement of the restorative materials. The
      present study was undertaken to assess the influence of the consistency of
      composite materials and the mode of application on voids and porosities in Class
      I adhesive restorations. METHODS: One hundred medium-sized Class I preparations
      with an adhesive design were restored with three composites of various
      consistencies using three different application modes. The restorations were
      sectioned, and each section of a restoration was inspected for the presence of
      voids. The total surface and the percentage of the cavity wall occupied by voids
      as well as the total number of voids in the sections were recorded. A Krusal
      Wallis analysis of variance was carried out on the data. Differences between
      individual composite materials for each mode of application and between
      individual application modes for each composite material were analyzed using a
      Mann-Whitney U-test at p < 0.05. RESULTS: The injection technique with a Hawe
      Neos Centrix tip was the best mode of application. Both smearing and the
      condensation of composites appeared to produce unreliable results. Furthermore,
      there were more problems with voids and wall adaptation for the thicker
      consistency composite than for the medium- and thin-consistency material.
      SIGNIFICANCE: The thick-consistency composite had more problems related to voids
      and wall adaptation than the medium- and thin-consistency composites.

PMID- 9002841
TI  - Micromorphological spectrum from overdrying to overwetting acid-conditioned
      dentin in water-free acetone-based, single-bottle primer/adhesives.
AB  - OBJECTIVES: The goal of this study was to illustrate and define the
      micromorphological spectrum which exists at the resin-dentin interface when two
      water-free, acetone-based, single-bottle primer/adhesive systems (One-Step,
      Bisco, and Prime & Bond, Dentsply/L.D. Caulk) were applied to acid-conditioned
      dentin under different dry and wet bonding conditions. METHODS: Forty-eight 1 mm
      dentin discs were each conditioned with 10% phosphoric acid and rinsed for 20 s.
      They were randomly divided into 4 groups based upon the status of the remaining
      surface moisture; Group I (30 s dry); Group II (3 s dry); Group III (blot dry)
      and Group IV (overwet). Bonded dentin disc pairs were then demineralized in EDTA
      and embedded in epoxy resin for transmission electron microscopic examination.
      RESULTS: The micromorphological spectra of the two bonding systems were
      essentially similar. Both were effected by even mild desiccation (3 s), resulting
      in incomplete intertubular resin infiltration. Optimal intertubular resin
      infiltration was achieved when the collagen network was kept moist and appeared
      relatively unaffected by the presence of excess surface moisture. On the other
      hand, intratubular resin infiltration was severely compromised in the presence of
      excess water within the dentinal tubules and at their openings in the dentin
      surface. The continuity of the resin layer deteriorated; blister-like spaces
      formed on the dentin surface and resin globules were found around the tubular
      orifices and on the surface of the hybrid layer. In addition, a complex phase
      separation pattern was observed in Prime & Bond that was characterized by phase
      inversion in the presence of surface moisture. SIGNIFICANCE: The "window of
      opportunity" for optimal interfacial integrity for both water-free systems
      appeared to depend upon keeping the demineralized collagen network moist, coupled
      with the complete evaporation of excess and "displaced" water from tissues prior
      to light-curing the prime/adhesives.

PMID- 9002842
TI  - Influence of film thickness on joint bend strength of a ceramic/resin composite
      joint.
AB  - OBJECTIVES: The purpose of this study was to evaluate the influence of different
      film thicknesses of resin composite luting agents on the joint bend strength of a
      ceramic/resin interface. METHODS: Mirage FLC (Chamelon Dental Products) and Vita
      Cerec (Coltene AG) duo cement were used in combination with the ceramic
      materials, Mirage and Vita Cerec blocks. Cement layers with thicknesses of 20
      microns, 50 microns, 100 microns and 200 microns were light-cured with a high
      intensity curing light. Ten specimens of each ceramic/cement combination and
      thickness provided a total of 80 complete test specimens. Each specimen was
      placed in a four-point bending jig mounted in a universal tensile testing machine
      and underwent loading. A paired two-tailed Student's 1-test was used to evaluate
      differences between different series of film thicknesses and resin cement
      combinations. RESULTS: Within each ceramic/cement combination, the bond strength
      values were significantly lower for the 20 micron film then the thicker films.
      SIGNIFICANCE: Taking into account the physical and clinical properties of resin
      based luting agents, available knowledge indicates that a marginal gap on the
      order of 50-100 microns seems to optimize performance.

PMID- 9002844
TI  - Monomers with low oxygen inhibition as enamel/dentin adhesives.
AB  - OBJECTIVES: This study was conducted to investigate the depths of polymerization
      inhibition by oxygen, the shear bond strengths to enamel and dentin, and the
      marginal adaptation in dentin cavities of experimental adhesives containing
      BisGMA/HEMA of mixtures of low-inhibition BisGMA-dicarbonate with HEMA or with
      HEMA-carbonate at ratios of 100/0, 80/20, 60/40, 50/50, and 40/60 by weight.
      METHODS: The inhibition layer thickness was determined microscopically as non
      polymerized surface film thickness on three samples each. For bond strength
      testing, composite cylinders were bonded to enamel and dentin following H3PO4
      conditioning with the adhesives dissolved in acetone; marginal adaptation was
      evaluated in cylindrical dentin cavities. Five specimens each were stored in
      water for 24 h prior to testing. Shear bond strength results were compared by
      ANOVA and Duncan's test (p < 0.05), the maximum gap widths by Kruskal-Wallis,
      ANOVA and Wilcoxon's two-sample test (p < 0.01). RESULTS: Inhibition layer
      thickness was significantly smaller for modified than for conventional
      BisGMA/HEMA monomers and increased significantly with HEMA content. In the BisGMA
      dicarbonate/HEMA-carbonate group, the inhibited layer was thinner than 1 micron.
      Apart from the 40 and 50% BisGMA-dicarbonate/HEMA-carbonate mixtures, enamel bond
      strengths were not significantly different. The highest bond strengths to dentin
      were 15 and 12 MPa at 50 BisGMA and 50 BisGMA-dicarbonates/HEMA, respectively.
      The average bond strength for the BisGMA-dicarbonate/HEMA-carbonate group was 5
      MPa. Adhesives with 40 and 60% HEMA in the conventional and 40 to 60% HEMA in the
      dicarbonate/HEMA group showed significantly better marginal adaptation than all
      others (p < 0.05). SIGNIFICANCE: Carbonate-modified low-inhibition monomers have
      no advantage as enamel/dentin adhesives compared with conventional BisGMA/HEMA
      based resins.

PMID- 9002843
TI  - Effect of phosphoric acid concentration on wet-bonding to etched dentin.
AB  - OBJECTIVE: This study was conducted to investigate the influence of phosphoric
      acid (H3PO44) demineralization of dentin during smear layer removal prior to
      dentin bonding. METHODS: Bovine dentin was pre-treated with either 10 wt% or 35
      wt% phosphoric acid for 30 s. Substrates were then rinsed and either kept moist
      or air-dried before a light-cured bonding system was applied. The adhesive system
      consisted of a 5 wt% 4-methacryloyloxyethyl trimellitate anhydride (4-META) in
      acetone primer, and a photocured bonding agent, 4-META/triethylene glycol
      dimethacrylate-camphorquinone/N-phenylglycine (4-META/TEGDMA-CQ/NPG). Tensile
      bond strengths of bonded specimens were measured, and specimens were examined
      with a scanning electron microscope (SEM). Data obtained were subjected to two
      way ANOVA and Duncan's New Multiple Range test to examine statistically
      significant differences (p < 0.05). RESULTS: Improved tensile bond strengths were
      measured when the 4-META/acetone primer was applied to wet dentin that had been
      etched with 10 wt% H3PO4 compared with similarly etched but dry dentin samples.
      However, when the dentin was etched with 35 wt% H3PO4, there was no significant
      difference in tensile bond strength between wet and dry specimens. SEM
      examination of the fractured surfaces revealed a number of cohesive failures in
      the demineralized dentin. Microscopic examination of cross sections of these
      surfaces indicated that resin impregnation was inadequate and that the hybrid
      layers in the cohesively fractured specimens were defective. SIGNIFICANCE:
      Phenomena observed in this investigation suggest that the channels between the
      H3PO4-denatured collagen fibers were difficult to preserve, so adhesive monomer
      impregnation of these substrates was impaired in a considerable number of test
      specimens.

PMID- 9002845
TI  - Morphological field emission-SEM study of the effect of six phosphoric acid
      etching agents on human dentin.
AB  - OBJECTIVES: This study evaluated the effects of six phosphoric acid-etching
      agents on dentin, the independent variables being two acid concentrations (10%
      and 32%-37%) and three thickener conditions (no thickener, silica, and polymer).
      The tested hypothesis was that the use of different etchants with similar
      concentrations of phosphoric acid would result in similar depths of dentin
      demineralization. METHODS: Thirty dentin disks were obtained from extracted human
      teeth by microtome sectioning. The dentin surfaces were etched with one of the
      etching agents, fixed, dehydrated and dried. The specimens were observed using a
      FE-SEM. The mean deepest demineralization of intertubular dentin was measured
      from fracture surfaces of the disks. These values were analyzed by ANOVA and
      Duncan's Test. The morphological appearance of the dentin surfaces was compared
      using the following observation criteria: 1) Presence of a cuff of peritubular
      dentin; 2) Relative thickness of the layer containing residual collagen or smear
      layer particles; and 3) Formation of a submicron hiatus at the bottom of the
      exposed collagen network. The pH of each of the etching agents was measured. A
      correlation analysis was made of the pH vs. the depth of dentin demineralization.
      RESULTS: Silica-thickened etchants did not demineralize dentin as deeply as did
      polymer-thickened etchants and unthickened etchants. High magnifications revealed
      three distinct zones within the demineralized dentin layer; an upper porous zone
      of residual smear layer or denatured collagen and residual silica particles (in
      groups etched with silica-thickened etchants), an intermediate area with randomly
      oriented collagen fibers, and a lower zone with submicron hiatus, few collagen
      fibers, and scattered hydroxyapatite inclusions. This hiatus was observable in
      all the specimens etched with the polymer-thickened etchants, in 90% of the
      specimens etched with the unthickened phosphoric acid liquids, and in 60% of the
      specimens etched with the silica-thickened gels. SIGNIFICANCE: The results
      obtained suggest that similar concentrations of phosphoric acid etchants
      containing distinct thickeners result in different demineralization depths as
      well as different morphology of etched dentin.

PMID- 9002846
TI  - Dental materials citations: Part A, January to June 1996.
AB  - OBJECTIVE: A search was conducted to identify the dental materials publications
      that appeared in biomedical journals from January 1996 to June 1996 and to
      compare the frequency of citations among the different categories. METHODS: The
      tables of contents of 16 primary journals and 48 secondary journals were examined
      to identify dental materials articles that were published from January to June
      1996. These citations were divided into 17 categories and the numbers of
      citations in each category were compared. To assess the usefulness of the
      citation listing, a survey of Academy of Dental Materials subscribers was
      conducted (n = 153 of 382 or 40.1% have responded to date). RESULTS: As in
      previous years, the greatest number of citations were found in categories of
      bonding (n = 83) and resin-based restorative materials such as composites and
      resin-reinforced glass ionomers (n = 80). Results of the reader survey indicated
      that 84.3% of the respondents have used the citations lists, and 95.4% feel that
      its publication should be continued. SIGNIFICANCE: The literature compiled in
      this list serves to supplement the electronic indexing mechanisms so that
      academicians and researchers can have ready access to the current literature in
      the field of dental materials.

PMID- 9002848
TI  - Short-term contamination of luting cements by water and saliva.
AB  - OBJECTIVES: The aim of this study was to determine the effect of water,
      artificial saliva and natural saliva on the hardening process of three dental
      luting cements. METHODS: Cement samples, 1 mm thick and 5 mm in diameter, were
      subjected to various storage conditions in an oven maintained at 37 degrees C.
      Some samples were aged in 100% humidity or water for up to 1 wk. The other
      samples were covered with water, artificial saliva or natural saliva at various
      times after mixing. The Knoop hardness values of the cement surfaces were
      measured. Differences between groups were evaluated with an ANOVA followed by a
      Tukey multiple comparison at the 5% level of significance. The hardness ratio of
      the contaminated samples was calculated using the 30 min mean KHN of the samples
      aged in 100% humidity as the divisor. RESULTS: The glass ionomer samples were
      significantly harder (48.3 +/- 3.8) than the zinc phosphate (38.9 +/- 7.5) or
      composite cements (35.4 +/- 10.2) after 1 wk in 100% humidity storage condition.
      When immersed in water, the hardness of both the glass ionomer and the zinc
      phosphate decreased to almost half that of the specimens stored in 100% humidity
      (26.2 +/- 2.7 and 16.9 +/- 2.5, respectively). Contamination decreased the
      hardness of zinc phosphate and glass ionomer (hardness ratio, water contamination
      at 5 min: 0.39 +/- 0.10 and 0.52 +/- 0.12, respectively) but had very little
      effect on the composite. Overall, water had a greater softening effect than
      artificial or natural saliva on the cements. SIGNIFICANCE: In light of these
      results, glass ionomer cement should be protected from water and saliva for the
      first 15 min after mixing.

PMID- 9002847
TI  - Irreversible hydrocolloids for crown and bridge impressions: effect of different
      treatments on compatibility of irreversible hydrocolloid impression material with
      type IV gypsums.
AB  - OBJECTIVES: The aims of this research were: 1) to determine if the compatibility
      between irreversible hydrocolloids (alginates) and type IV gypsums (die stones)
      is affected by different treatments of the impressions before pouring, and 2) to
      present a rating system based on Ryge's system for clinical evaluation in order
      to classify the quality of gypsum casts using detail reproduction and surface
      structure as criteria. METHODS: Impressions were taken on a Plexiglas staircase
      (heights of the steps 15-82 microns) with six irreversible hydrocolloids designed
      for crown and bridge and ten type I and II irreversible hydrocolloids.
      Impressions of each brand were divided into four groups. One group was treated
      with 2% potassium sulfate, the second with water, the third with an alginate
      stabilizer, Sorbanat (Guilini Chemie), and as a control, a fourth group which was
      not allowed to come into contact with any liquid, i.e., the impressions were
      poured dry. The differently treated impressions were poured with ten type IV
      gypsums. The quality of all gypsum casts was then judged according to the rating
      system. RESULTS: All the irreversible hydrocolloids, if correctly treated before
      pouring with a compatible gypsum, could reproduce details of 20 microns. Detail
      reproduction did not improve with the use of 2% potassium sulfate solution
      compared to water or if the impressions were poured "dry". In general, the
      alginate stabilizer produced casts with significantly better detail reproduction
      and surface structure. SIGNIFICANCE: The results show that dentists and dental
      technicians need to know how each specific irreversible hydrocolloid should be
      treated and also with which type IV gypsum it is compatible. This research also
      indicates that an irreversible hydrocolloid impression should not come into
      contact with any liquid within the first 15 min.

PMID- 9002849
TI  - Fluoride release profiles of restorative glass ionomer formulations.
AB  - OBJECTIVES: The amounts of fluoride released by different glass ionomer
      formulations were compared on the basis of individual fluoride release profiles
      in order to derive the effect of the physical and chemical formulation on the
      fluoride release process. METHODS: The fluoride release profiles of each of five
      specimens of ten glass ionomer cements setting by an acid-base reaction were
      investigated. The profiles were obtained by determining the amount of fluoride
      released [F] after equilibrating the samples at 37 degrees C in distilled water
      for 140 d. The [[F],t]-profiles were compared with a Multivariate Data Analysis
      on the basis of a Principal Component Analysis. RESULTS: The Multivariate Data
      Analysis reveals that eight of the ten glass ionomers can be classified into four
      distinct groups. When the cumulative amount of fluoride released by each sample,
      [F]c, is calculated and fitted as a function of time, a regression analysis (r >
      0.99) reveals that [F]c for all samples is most adequately represented by [F]c =
      ([F]l x t)/(t + t1/2) + beta x square root of t, indicating that two kinetic
      processes are responsible for the fluoride release profiles. SIGNIFICANCE: A
      comparison of the parameters of this equation shows that the physicochemical
      rationale for the classification of the glass ionomers conforms to differences in
      the kinetics of these processes which are determined by the qualitative and
      quantitative chemical composition as well as by the presentation (hand-mixed vs.
      capsules) of the glass ionomer. From the classification, it becomes apparent that
      different formulations can result in the same fluoride release profiles.

PMID- 9002850
TI  - Penetration of etching agents and its influence on sealer penetration into
      fissures in vitro.
AB  - OBJECTIVES: This study was designed to assess: 1) the ability of several
      commercially available and laboratory-made acid etchants to penetrate occlusal
      fissures when used for pit and fissure sealing, and 2) the influence of adding a
      surfactant to the etchant on penetration of the sealer. Viscosity, surface
      tension and contact angle to enamel of the etchants were determined for each
      treatment, and these properties were related to the etchant's ability to
      penetrate fissures. METHODS: Penetration was assessed in an acrylic fissure model
      having a deep-narrow fissure using a microscope and a chronometer. Penetration
      depth was expressed as percentage of total fissure depth and was measured in
      intervals up to 90 s. Commercially available etching agents with different
      viscosities and two solutions of phosphoric acid (37%), one with and one without
      a surfactant, were tested. The etch pattern obtained on the fissure wall enamel
      of extracted teeth with some of these products was evaluated using scanning
      electron microscopy. Eventually, the penetration depths of a composite sealer in
      fissures treated with a conventional etchant were compared to those after
      application of a surfactant-containing etchant on sections of extracted teeth.
      RESULTS: None of the commercially available etchants studied were able to
      penetrate farther than 17% of the total fissure depth in the fissure model. The
      surfactant-containing etchant showed complete penetration within about 1 min and
      had a significantly lower surface tension and contact angle than the other
      products tested. Only the surfactant-containing etchant could produce a retentive
      pattern on the entire wall enamel of the fissure with the exception of locations
      blocked by debris and plaque. Fissures treated with this product prior to sealing
      showed a significantly deeper penetration of the sealer in deep-marrow fissures.
      SIGNIFICANCE: Surfactant-containing etchants with a low viscosity can penetrate
      completely into fissures and can produce an increased retentive and wettable
      surface which significantly increased sealant penetration into deep fissures.

PMID- 9002851
TI  - In vitro wear, hardness, and conversion of diacetyl-containing and propanal
      containing resin materials.
AB  - OBJECTIVES: This study was conducted to determine the effect of diacetyl or
      propanal activities: 1) on the in vitro wear of 22 experimental resin composites;
      and 2) on the Wallace indentation hardness of the unfilled resins. The objective
      was to examine the correlation between wear, hardness, and quantity of remaining
      double bonds (determined previously). METHODS: Diacetyl or propanal agents were
      added in varying concentrations to monomer mixtures. The resins were made light
      curing and those used for measurement of wear were loaded with filter. The
      results were analyzed by ANOVA and Newman-Keuls' multiple range tests. RESULTS:
      In the composite systems, adding diacetyl or propanal resulted in decreased in
      vitro wear. The quantity of remaining double bonds in the dental polymers with
      these additives was also reduced. Their effect on Wallace indentation depth was
      less clear-cut. Low concentrations of additives decreased indentation depth of
      the unfilled materials, whereas high concentrations increased indentation depth.
      If it assumed that differences in the polymer have a major influence on the wear
      when the filter content and particle matrix interface are kept constant, then the
      hardness data on the unfilled resin can be used to correlate property changes of
      the polymer in the composite. A three-dimensional regression analysis found that
      in vitro wear decreased with decreasing Wallace indentation depth and decreasing
      quantity of remaining double bonds. SIGNIFICANCE: Addition of diketone or
      monoaldehyde to resin monomers may provide a means of increasing wear resistance
      of composites and allow their use in stress-bearing areas.

PMID- 9002852
TI  - Dentin shear strength: effects of tubule orientation and intratooth location.
AB  - OBJECTIVES: Dentin has a highly oriented tubule structure, and the tubule number
      density and area fraction of intertubular dentin vary with distance from the
      pulp. This investigation sought to determine the influence of tubule orientation
      on shear strength of dentin from samples derived at various intratooth locations.
      METHODS: Third molars were sectioned and prepared to provide samples from two
      locations (center and cusp) and with one of three specific tubule orientations.
      In series 1, matched pairs of midcoronal samples were tested using two tubule
      orientations. A paired t-test was used for statistical analysis. In series 2,
      three samples from central and cuspal areas were tested using three different
      tubule orientations. A two-day ANOVA was used for statistical analysis. Each
      sample had dimensions of approximately 1 x 1 x 5 mm and was tested in a hydrated
      state by a single plane lap shear method. RESULTS: The paired dentin samples of
      the midcoronal dentin in the two orientations had shear strengths of 72.4 +/-
      15.6 MPa and 78.4 +/- 13.2 MPa, and were not significantly different (p > 0.05;
      paired t-test). In the second series, samples from the center location with
      tubules parallel to the shear plane with applied force in directions rotated by
      90 degrees did not exhibit a significant difference (p > 0.05), with an average
      value of 53.5 +/- 9.5 MPa. Samples oriented with tubules along the long axis of
      the specimen and tested with shear force applied perpendicular to the tubule
      direction had significantly higher (p < 0.05; two-way ANOVA) shear strength (78.0
      +/- 8.5 MPa). The specimens from the cusp area did not exhibit a statistically
      significant difference (p > 0.05; two-way ANOVA) with respect to the three
      orientations (83.6 +/- 8.4; +/- 13.8; 91.8 +/- 12.7 MPa). Cuspal areas were
      stronger than central areas in two of the three orientations tested.
      SIGNIFICANCE: Results indicated that the shear strength differs in central and
      cusp areas and is dependent on dentin tubule orientation in the central area.
      Shear strengths were much larger than values reported in shear bond strength
      tests. This suggests that dentin shear strength is far in excess of dentin bond
      strengths using shear tests, and that fractures through dentin in such result
      from flaws or stress concentration in the dentin.

PMID- 9002854
TI  - Influence of tooth cryopreservation and storage time on microleakage.
AB  - OBJECTIVES: This study was conducted to compare microleakage of two new dentin
      bonding agents on freshly extracted teeth, cryopreserved teeth, or teeth stored
      in water containing 0.5% chloramine at 4 degrees C. METHODS: Rectangular Class V
      cavity preparations were made on the buccal and the lingual surface of wisdom
      teeth. They were filled with either Scotchbond Multi-Purpose and Z100 (3M Dental
      Products) or with Gluma 2000 and Pekafill (Bayer Dental). After thermocycling,
      silver staining penetration was evaluated under a light microscope. SEM
      examination and EDX analysis were performed to evaluate the microleakage pattern.
      The results were analyzed by the use of a two-way analysis of variance. RESULTS:
      Cryopreservation for 13 wk or 12 d refrigeration did not produce changes in the
      amount of microleakage. However, 48 d or longer of refrigeration increased
      microleakage. There was no correlation between changes in microleakage and
      storage time. Specimens prepared with both dentin bonding agents exhibited the
      same microleakage values and the same microleakage pattern. SIGNIFICANCE:
      Refrigeration at 4 degrees C in 0.5% chloramine for 48 d or longer may cause an
      increase in microleakage. Cryopreservation for 13 wk or short-term refrigeration
      did not affect the microleakage.

PMID- 9002853
TI  - The influence of simulated clinical handling on the flexural and compressive
      strength of posterior composite restorative materials.
AB  - OBJECTIVES: The aim of this study was to investigate the influence of clinical
      handling on the flexural and compressive strengths of two commercially available
      posterior composites. METHODS: Since the manufacturing of test specimens in a
      truly clinical situation presents many problems, an in vitro model was developed,
      consisting of a phantom-head set-up in a clinical operatory. Two composite
      materials, recommended for use in posterior teeth, were used: P50 APC (3M Dental
      Products) and Herculite XRV (Kerr, Dental Manufacturing). Beam specimens for 3
      point bending tests of both materials and cylindrical specimens for compression
      test of P50 were made both under ideal laboratory circumstances and under
      simulated clinical circumstances. RESULTS: The difference in mean flexural
      strength between laboratory prepared and the quasi-clinically prepared specimens
      was highly significant for both the specimens handled in a clinical manner was
      15% of the flexural strength of the P50 specimens made under laboratory
      conditions, and the difference for Herculite XRV was 29%. No difference in
      compressive strength could be shown between the laboratory-fabricated and the
      quasi-clinically made specimens of P50. SIGNIFICANCE: The relative flexural
      strength of composite materials in a clinical situation may differ significantly
      from that predicted from mechanical properties measured in vitro.

PMID- 9002855
TI  - Review of dental materials citations: Part B, July to December 1995.
AB  - OBJECTIVE: A lag of many months occurs between journal issue publication and
      updates to electronic databases. The objective of this literature analysis was to
      identify and categorize all of the dental materials citations in biomedical
      journals that were published from July 1995 through December 1995. METHODS:
      Seventeen primary and 51 secondary journals were searched using their tables of
      contents to detect and record dental materials publications from July to December
      of 1995. Those journals that were typically rich in dental materials articles
      were classified as primary ones. Citations were categorized into 17 topics and
      divided into subsections. The review excluded case reports, most literature
      related primarily to dental implants, and most articles on biomedical materials
      used outside of the field of general dentistry. RESULTS: The greatest number of
      citations was related to topics of dentin bonding and resin-based restorative
      filling materials (composites and glass ionomers). There was no major change in
      the number of dental materials publications per year reported from 1993 (n = 786)
      to 1995 (n = 751). SIGNIFICANCE: This citation list provides a comprehensive
      resource for use by academicians and researchers to bridge the gap between
      initial publication and access to electronic searching methods for major
      databases.

PMID- 9002856
TI  - Corrosion of amalgams under sliding wear.
AB  - OBJECTIVES: During mastication, dental amalgams are simultaneously subjected to
      corrosion by the oral environment and to a sliding-wear process by biting forces.
      In the present study, the effect of sliding wear on the corrosion behavior of two
      high-copper dental amalgams was investigated. METHODS: An experimental apparatus
      was utilized that allows electrochemical testing under sliding-wear conditions.
      Corrosion potential measurements and anodic polarization scans were conducted in
      0.1 M NaCl solution under sliding wear to characterize the behavior of two
      commercial, high-copper, single composition dental amalgams. In addition, long
      duration tests were conducted to assess possible corrosion and wear synergistic
      effects. RESULTS: The results showed that sliding wear caused a sharp reduction
      in the corrosion potential, a significant increase in the corrosion rate and a
      decrease in the repassivation rate of both amalgams. These effects are due to the
      mechanical removal by the wear process of the surface protective film formed on
      dental amalgams. The simultaneous action of sliding wear and corrosion can also
      induce embrittlement that leads to cracking. SIGNIFICANCE: The present evidence
      suggests that this cracking may be one of the major contributors to marginal
      failures of dental amalgam restorations.

PMID- 9002857
TI  - Cyclic voltammetry of dental amalgams.
AB  - OBJECTIVES: This study used cyclic voltammetry to examine the effect of the
      composition of dental amalgams on their electrochemical behavior, including
      reactions occurring outside of oral conditions. METHODS: Amalgams (residual
      mercury 47.5%) were prepared using two low-copper (3 wt% Cu) powders and five
      high-copper powders (40-80 wt% Ag, 12-30 wt% Cu) with and without zinc (1.5 wt%).
      Cyclic voltammograms were obtained at 37 degrees C in 1.0% NaCl scanning at 2
      mV/s in the potential range from -1.5 V to +0.8 V vs. Ag/AgCl. RESULTS: During
      the anodic scans, AgCl and Hg2Cl2 films were formed on all amalgams except the
      one with only 40 wt% Ag. In all high-copper amalgams, a prominent Cu (oxidation)
      peak was found at -0.1 V, indicating the release of copper during corrosion. Zinc
      affected the oxidation process for both low- and high-copper amalgams. When zinc
      was absent, a peak for Sn2+ oxidation appeared at -0.4 V. When zinc was present,
      a Sn4+ oxidation peak was revealed at -0.6 V. In some amalgams, there was
      evidence of the selective corrosion (pitting corrosion) of tin and copper. In the
      lowest silver-content amalgam, no protective films were formed, which is
      indicative of its poor corrosion resistance. As expected, in all the low-copper
      amalgams, an extreme increase in current density was recorded immediately at 0 V,
      due to the release of tin from gamma 2. SIGNIFICANCE: Cyclic voltammetry is
      useful for the rapid examination (less than an hour) of the electrochemical
      behavior of amalgams, specifically to obtain information on the formation of
      compounds and the sequences of electrochemical reactions.

PMID- 9002858
TI  - Resin-modified glass ionomer cements: bonding to enamel and dentin.
AB  - OBJECTIVES: This study was designed to investigate the effect of storage in water
      on bonding efficacy to enamel and dentin of four resin-modified (Dyract, De Trey
      Dentsply; Fuji II LC, GC Dental Corp.; Photac Fil, ESPE; Vitremer, 3M Dental
      Products), one conventional glass ionomer filling material (Ketac Fil, ESPE) and
      a resin composite system (Pekafill/Gluma bonding system, Bayer). The hypothesis
      was that water storage would lead to an adverse effect on bond strength of resin
      modified glass ionomer cements to enamel and dentin. METHODS: The shear bond
      strength of each material was determined after storage periods of 24 h, 1 wk, 1
      mon, 3 mon and 6 mon. The data were subjected to one-way ANOVA. Significant
      differences were determined by multiple comparison testing (significance level
      5%). The failure modes of the debonded specimens were analyzed with a dissecting
      microscope. RESULTS: Shear bond strengths to enamel for Dyract, Photac Fil and
      Pekafill were 5.2 +/- 1.3, 9.9 +/- 1.6 and 17.0 +/- 2.3 MPa, irrespective of
      storage time (p > 0.05). For Ketac Fil, the average shear bond strength between 1
      wk and 6 mon was 4.5 +/- 1.7 MPa, the mean value for Fuji II LC between 24 h and
      3 mon was 10.3 +/- 3.9 MPa and after 6 mon was 19.8 +/- 4.4 MPa, while Vitremer
      showed increasing shear bond strengths between 24 h (2.4 +/- 0.8 MPa) and 1,3 and
      6 mon (13.8 +/- 4.3 MPa). Shear bond strengths to dentin were not adversely
      affected by storage throughout the 6 mon for Dyract (13.0 +/- 2.6 MPa), Fuji II
      LC (12.7 +/- 1.7 MPa) and Pekafill (14.6 +/- 3.1 MPa), when tested by ANOVA (p >
      0.05). Ketac Fil showed 4.9 +/- 1.2 MPa between 1 wk and 6 mon and lower shear
      bond strength after 24 h. The average shear bond strengths up to 1 mon for
      Vitremer were 5.4 +/- 2.5 MPa (p > 0.05). However, at 3 and 6 mon immersion in
      water, three specimens had loosened spontaneously. With Photac Fil, no adhesion
      to dentin was registered. Most samples showed cohesive failure patterns in the
      restorative materials. Adhesive or mixed failures were registered only for
      Vitremer on dentin and enamel up to 1 wk and for Dyract on enamel. SIGNIFICANCE:
      Long-term water storage generally had no adverse effect on bonding efficacy of
      resin-modified glass ionomer cements to dentin and enamel.

PMID- 9002859
TI  - Effect of corrosion on the strength of soldered titanium and Ti-6Al-4V alloy.
AB  - OBJECTIVE: Finding an optimal soldering system for a titanium prosthesis has
      become increasingly important with the successful introduction of titanium and
      titanium alloys to dentistry. This study examined the effect of corrosion on the
      strength of the soldered joints of pure titanium and Ti-6Al-4V alloys joined
      using various solders. METHODS: Commercially pure titanium and Ti-6Al-4V alloy
      rods (2 mm in diameter; 25 mm long) were soldered in an argon atmosphere using
      four solders: two kinds of titanium-based solder, a gold-based solder, and a
      silver-based solder. Tensile strengths were examined before or after immersion
      treatments. Specimens were immersed in either a 0.9% NaCl or 1.0% lactic acid
      solution held at 35 degrees C for 3 and 8 wk. The amounts of various metal
      elements released were determined by atomic absorption photospectroscopy. The
      natural potentials and potentiodynamic polarization behavior of the soldered
      specimens in 0.9% NaCl or 1.0% lactic acid were determined by a computer-assisted
      corrosion measurement system. The results were analyzed by ANOVA and Student's t
      test. RESULTS: The cp-titanium and Ti-6Al-4V samples soldered with titanium-based
      solders exhibited tensile strengths of 300-400 MPa and were not significantly
      affected by immersion in either solution (no significant difference at p < 0.05).
      The strengths of both the cp-titanium and titanium alloy specimens soldered with
      gold-based solder were significantly lower than for any of the other specimens
      and were affected by immersion in the 0.9% NaCl solution (p < 0.01). The cp
      titanium and Ti-6Al-4V specimens that were soldered with titanium-based solders
      did not show any transpassive regions or breakdown in the natural electrode
      potential range. On the contrary, the specimens soldered with gold-based and
      silver-based solders showed transpassive regions or breakdown potentials at less
      than 0 mV in 0.9% NaCl solution. SIGNIFICANCE: It is recommended that titanium
      based solder be employed for titanium and titanium alloys.

PMID- 9002860
TI  - An FTIR study on the setting mechanism of resin-modified glass ionomer
      restoratives.
AB  - OBJECTIVES: An experimental method was used to assess the glass ionomer and
      resinous character in three "dual-cure" (Fuji II LC, Photac-Fil, Variglass) and a
      "triple-cure" (Vitremer) resin-modified glass ionomer restoratives to evaluate
      their acid-base and free-radical setting mechanisms. METHODS: Four groups (A-D)
      of three specimens (5 x 4 x 1 mm) were prepared from each material and subjected
      to the following treatments: A: mixing; B,C: mixing, 60 s irradiation, 20 min
      dark/dry storage; and D: mixing, 20 min dark/dry storage and then 60 s
      irradiation. Micro-multiple internal reflectance FTIR spectroscopy was used to
      determine: 1) the curing efficiency of the products immediately after
      irradiation; 2) the effect of irradiation 20 min after dark/dry storage on the
      curing efficiency; and 3) the extent of the acid-base reaction on irradiated and
      non-irradiated specimens after 20 min dark/dry storage. RESULTS: The curing
      efficiency immediately after irradiation was determined from the percentage of
      residual double bonds which ranged from 33-50% for these materials. Irradiation
      after 20 min dark/dry storage significantly reduced curing efficiency in all the
      products, except Variglass. The latter showed no acid-base reaction under the
      conditions of this study. Non-irradiated specimens after the dark storage period
      demonstrated higher carboxylate yields compared to their irradiated analogues.
      Non-irradiated specimens from Vitremer had the highest carboxylate yield and a
      curing efficiency of approximately 50% residual double bonds. SIGNIFICANCE:
      Photopolymerization seemed to greatly reduce the acid-base reaction during the
      early setting stages of resin-modified glass ionomer restoratives. The free
      radical formation rates are slower than those achieved by chemically initiated
      polymerization, but they produce adequate conversion and high carboxylate salt
      yields. This study demonstrated an experimental model for identification and
      characterization of the acid-base reaction in water-containing resinmodified
      glass ionomer restoratives.

PMID- 9002861
TI  - Equilibrium vapor pressure of mercury from dental amalgam in vitro.
AB  - OBJECTIVES: The purpose of this study was to acquire reliable quantitative data
      on mercury vapor pressure above the surface of dental amalgam samples in both the
      as-formed and the abraded state. METHODS: The equilibrium vapor pressure of
      mercury from dental amalgam was obtained using residual gas analysis in
      conjunction with a quartz crystal microbalance. The measurements were performed
      under ultrahigh-vacuum conditions. RESULTS: Using the residual gas analyzer, the
      average mercury vapor pressures measured from the as-formed and abraded dental
      amalgam surfaces were 8 x 10(-7) and 1.7 x 10(-4) Pa, respectively. The
      corresponding vapor densities are: 6 x 10(-2) micrograms/m3 and 14 micrograms/m3.
      The average mercury vapor pressures measured from the as-formed and abraded
      dental amalgam surfaces using the quartz crystal microbalance were: 2.4 x 10(-6)
      and 1.0 x 10(-4) Pa, respectively. The corresponding vapor densities are: 0.2
      microgram/m3 and 8 micrograms/m3. SIGNIFICANCE: This project provides a
      measurement of the equilibrium vapor pressure of mercury from as-formed and
      abraded amalgam surfaces. By definition, the equilibrium vapor pressure provides
      the maximum density of mercury which can be present in the environment above the
      amalgam. The vapor density of mercury within the oral cavity must be less than
      this value due to the dynamic nature of the system.

PMID- 9002862
TI  - In vitro models of biocompatibility: a review.
AB  - The objectives of this paper were to define in vitro biocompatibility of
      materials, to discuss some of the issues concerning why conclusions from tissue
      culture are sometimes different from in vivo biocompatibility, to give highlights
      of the sequence of the development of these in vitro assays from the early 1950s
      to their present state of development, and to discuss possible future trends for
      in vitro testing. In vitro biocompatibility tests were developed to simulate and
      predict biological reactions to materials when placed into or on tissues in the
      body. Traditional assays have measured cytotoxicity by means of either an end
      stage event, (i.e., permeability of cytoplasmic membranes of dead and dying
      cells, or some metabolic parameter such as cell division or an enzymatic
      reaction). In vitro assays for initiation of inflammatory and immune reactions to
      materials have also begun to appear in the literature. More recently, the concept
      of dentin barrier tests has been introduced for dental restorative materials.
      Four models which measure both permeability and biological effects of materials
      are compared and discussed. Future efforts may be directed toward development of
      materials which will allow or promote function and differentiation of tissues
      associated with materials. New analytical procedures and understanding of optimal
      characteristics of materials should improve our ability to develop more
      biocompatible materials. Both molecular biology techniques, and altered design of
      material surfaces may make the materials either more or less reactive to the
      biological milieu. These trends suggest a greater future role of the biological
      sciences in the development of biomaterials.

PMID- 9002863
TI  - Modeling the caries-inhibitory effects of dental materials.
AB  - The objectives of this review are to compare the models that are used to simulate
      the caries process in cardiology research and to suggest how these models might
      be used to assess caries-inhibitory properties of dental materials. Available
      caries-simulation models fall into the following classifications: 1) in vitro
      demineralization using acid buffers, 2) in vitro demineralization using
      bacterially generated acids, 3) in vitro demineralization/remineralization using
      a pH-cycling system, 4) an artificial mouth where a bacterially generated acid
      challenge is interspersed with a "saliva" treatment, 5) in vivo animal model
      (generally with rats), 6) in situ demineralization and/or remineralization using
      enamel or dentin blocks or slices in the human mouth, and 7) in vivo studies
      using teeth scheduled for extraction in the human mouth. Most dental materials
      studies have used simple in vitro demineralization models or component release
      experiments, each of which is inadequate to answer the questions that are being
      asked about the caries-inhibitory properties of the material being tested.
      Experimental methods must be chosen with care to ensure that the material to be
      tested is examined in an appropriate mode. The ultimate goal is to correctly
      predict clinical outcomes. The design or redesign of a model must eventually be
      tied to documented clinical outcomes to improve the model and allow for future
      successful development of new materials.

PMID- 9002864
TI  - Bioengineering seeds of contemplation: a private practitioner's perspective.
AB  - In a precise semantic sense, the most significant biomaterial in dentistry is the
      human tooth. How it reacts, changes and is affected during the dynamics of
      occlusal loading should be reexamined in light of modern technology. Much is
      known about the embryology, histology, biochemistry, anatomy, and the
      microbiology affecting teeth; however, there are areas of biomechanics,
      biochemistry, and bioelectricity which also affect dental hard tissues that
      remain largely unexplored. Technological advances enable us to use more
      sophisticated instrumentation to measure and quantify changes that occur during
      the dynamics of occlusal activity. Armed with this information, dentistry can
      better understand how teeth interact with restorative materials in order to
      increase the longevity of both.

PMID- 9002865
TI  - Considerations for modeling.
AB  - There has been a great growth in the biophysical knowledge base of the human
      masticatory system, which increases the chances of success in numerical and
      experimental modeling of the oral environment. The chief advances in
      understanding are in the areas of the dentino-enamel complex, the force-movement
      cycle of the mandible, mastication, comminution and salivary lubrication. These
      areas are reviewed, and suggested average clinical conditions are offered as a
      starting point for experiments in laboratory clinical simulation as it relates to
      the studies in biomaterials and biomechanics in dental research.

PMID- 9002866
TI  - Biochemical and physiological considerations for modeling biofilms in the oral
      cavity: a review.
AB  - This review describes some of the biochemical and physiological factors that
      should be considered in designing in vitro models of the oral cavity. The
      significance of the non-Newtonian properties and internal structures of saliva
      are reported as well as the ability of saliva to form biological films on all
      types of solid surfaces. The presence of compositional biochemical variations
      between absorbed salivary films is discussed for solid surfaces having different
      surface chemistries. The significance of the presence of small amounts of organic
      material in enamel and dentin is also stressed. Finally, by selecting other, more
      easily available secretional products than saliva, more relevant model systems
      for materials testing in vitro may be established than if only simple aqueous
      salt solutions are used.

PMID- 9002867
TI  - Effect of desiccation on microleakage of five Class 5 restorative materials.
AB  - Resin-modified glass ionomers, combinations of resin and glass-ionomer chemistry,
      have resulted in materials with longer working times and command set by visible
      light activation. These materials are easier to use and more resistant to early
      moisture contamination and fracture. A glass-ionomer or resin-modified glass
      ionomer restoration may be inadvertently desiccated by isolation of the same
      quadrant for subsequent restorative procedures. The present study is an
      assessment of the effects of desiccation on microleakage of three resin-modified
      glass-ionomers: Vitremer, Photac-Fil, Fuji II LC; a glass-ionomer, Ketac-Fil; and
      a microfill resin, Silux Plus. Fifty extracted molars were prepared with class 5
      preparations buccal and lingual and randomly assigned to 10 groups (n = 10).
      Restorations were placed according to the manufacturers' specifications and
      finished wet after the manufacturers' specified setting interval. All samples
      were thermocycled 300 cycles between 50 and 500 degrees C. Samples were stored in
      water at all times until the five groups to be desiccated were air dried and
      stored dry for 45 minutes. Desiccated groups were then rehydrated for 24 hours
      prior to AgNO3 staining. Teeth were sectioned mesiodistally and four buccolingual
      sections (0.6 mm thick) through each class 5 restoration were obtained with a
      Silverstone-Taylor hard tissue microtome. Each section was scored on a scale of 0
      4 for microleakage, and the highest score for dye penetration was used as the
      score for that restoration. An increase in microleakage was observed in all
      desiccated groups. Three materials showed a statistically significant increase in
      microleakage (P < 0.05) following desiccation. Microleakage increases following a
      brief period of desiccation corresponding to typical treatment times indicate
      that clinicians need to protect previously placed restorations from undue drying
      during subsequent dental treatment.

PMID- 9002868
TI  - Effect of triturator speed variation on physical properties of encapsulated glass
      ionomer luting cements.
AB  - This in vitro study evaluated the effect of variation of triturator mixing speed
      on the physical properties of two encapsulated glass-ionomer luting cements.
      Physical properties evaluated were working time, setting time, film thickness,
      and 24-hour and 7-day compressive strengths. Encapsulated glass-ionomer luting
      cements were mixed at 3000, 3500, 4000 (control), and 4500 cycles per minute
      (cpm). An oscillating rheometer was used to determine working and setting times.
      Film thickness and compressive strength were determined using methods described
      in ANSI/ADA Specification No 66 for dental glass-ionomer cements. Results of the
      study indicated that decreased mixing speed may prolong working and setting times
      for Ketac-Cem Maxicap and Fuji Cap I. Within the range of 3500 to 4500 cpm,
      variations in mixing speed do not significantly affect compressive strength or
      film thickness values for either cement. Excessively slow mixing speed (3000 cpm)
      often resulted in the presence of unmixed powder expressed from the capsule
      nozzle prior to the expression of mixed cement. The presence of this unmixed
      powder results in a decreased powder/liquid ratio, which may have an adverse
      effect on the physical properties of the set cement.

PMID- 9002869
TI  - Surface roughness of light-activated glass-ionomer cement restorative materials
      after finishing.
AB  - The purpose of this study was to compare the effect of various finishing
      sequences on the surface roughness of four new light-activated (LAGIC)
      restorative materials. Restorative materials included a polyacid-modified
      composite resin (Variglass VLC) and three resin-modified glass-ionomer cements
      (Vitremer, Photac-fil, and Fuji II LC). Thirty specimens of each material were
      prepared in Macor dies and randomly divided into six finishing sequence groups (n
      = 5): (1) Mylar strip (control), (2) carbide bur/Sof-Lex XT disks, (3) ET
      finishing diamonds, (4) carbide bur/Enhance polishing system, (5) carbide
      bur/Politip rubber finishers, and (6) carbide bur alone. Average surface
      roughness (Ra) in micrometers was measured with a Mitutoyo Surftest 401 Surface
      Roughness Tester and the data compared using ANOVA, Student-Newman-Keuls Multiple
      Comparison tests, and Dunnett's test at P < or = 0.05. Surface topography was
      also assessed using the scanning electron microscope (SEM) on epoxy replicas from
      samples of each group. The Mylar strip produced the smoothest surface and
      finishing sequences; (2) and (3) were significantly smoother than (4), (5), and
      (6). There were no significant differences between restorative materials when all
      finishing sequences were combined. SEM analysis was consistent with the
      profilometer results. Materials with higher (Ra) values appeared to have rougher
      surfaces. Rubber abrasives and polishing pastes seem to preferentially remove the
      polysalt and resin matrix of these materials.

PMID- 9002870
TI  - Influence of bonded amalgam restorations on the fracture strength of teeth.
AB  - This study evaluated the effect of bonded amalgam on the fracture strength of
      teeth using five adhesive systems: Panavia 21, Amalgambond Plus, Imperva Dual
      Bond, All-Bond 2 Primer/Bonding Resin, and All-Bond 2 Primer/Liner F. Intact
      teeth and amalgam lined with Copalite were used as control groups. Large MOD
      preparations were made in 20 extracted maxillary premolars for each group. The
      teeth were restored with Tytin. All groups were stored in water at 37 degrees C
      for 15 days and thermocycled 2500 times, over 8-48 degrees C. The specimens were
      preloaded five times in compression to 10 kg using a 5 mm-in-diameter,
      cylindrical steel indenter that contacted the teeth only on the cuspal inclines.
      Then the teeth were loaded to failure at 5.0 mm/min. The failure mode was
      recorded (amalgam failure, cusp fracture, or failure at the tooth/amalgam
      interface). The mean fracture strengths were analyzed using ANOVA and Newman
      Keuls multiple comparisons. The Imperva Dual Bond group showed the highest mean
      forces followed by All-Bond 2 Primer/Bonding Resin. The All-Bond 2 Primer/Liner F
      and Amalgambond Plus groups demonstrated lower means and were not significantly
      different from the Copalite group. The Panavia 21 group was in between these two
      groups and was not statistically different from either group. The mean strength
      of intact teeth was the highest, but its very large coefficient of variation
      (60%) prevented effective use of these data for statistical comparison. Analysis
      of the mode of fracture showed that Panavia 21, All-Bond 2 Primer/Bonding Resin,
      and Amalgambond Plus failed cohesively in the amalgam in 35%, 25%, and 15% of the
      specimens respectively. This fracture type is a good indication of effective
      bonding between tooth and amalgam. The most common type of fracture for all the
      restored groups was the one that occurred at the tooth/restoration interface.
      This would suggest that current bonding procedures could be improved.

PMID- 9002871
TI  - Effect of dentin primer on the shear bond strength between composite resin and
      enamel.
AB  - The purpose of this investigation was to determine the effect of dentin primers
      from Scotchbond Multi-Purpose, ProBond, All-Bond 2, and Syntac on the shear bond
      strength of composite resin to etched enamel. Two groups of extracted human molar
      teeth with flattened enamel surfaces (n = 12) were randomly assigned to each
      enamel/dentin bonding system. Following manufacturers' instructions enamel
      surfaces were etched, rinsed, and dried. Composite bonding procedures were
      conducted similarly in both groups for each enamel/dentin bonding system, except
      that in one of the two groups, dentin primer was applied prior to adhesive resin
      and composite placement. Samples were thermocycled and tested in shear until
      failure. Fracture analysis was performed on enamel surfaces with both light and
      scanning electron microscopy. Shear bond values (Mean +/- SD, MPa) were:
      Scotchbond Multi-Purpose unprimed 22.4 +/- 3.2, primed 17.9 +/- 5.9; ProBond
      unprimed 19.4 +/- 6.2, primed 18.3 +/- 3.3; All-Bond 2 unprimed 19.0 +/- 3.6,
      primed 17.3 +/- 3.0; and Syntac unprimed 26.2 +/- 9.0, primed 22.0 +/- 5.4. The
      only significant difference found between primed and unprimed groups was with
      Scotchbond Multi-Purpose, though there was a trend for primer application to
      decrease enamel bond strengths. Fracture surface analysis revealed that most
      failures were cohesive within the composite resin. These data suggest that the
      effect of primer on bonded composite resin to etched enamel is material specific.

PMID- 9002873
TI  - Immunogenicity of Actinobacillus actinomycetemcomitans serotype b-specific
      polysaccharide-protein conjugate.
AB  - To enhance the immunogenicity of capsular-like serotype b-specific polysaccharide
      antigen (SPA) of Actinobacillus actinomycetemcomitans, the purified antigen was
      coupled with bovine serum albumin via an adipic acid hydrazide functional group.
      The conjugate (SPA-bovine serum albumin) or the native SPA was administered
      subcutaneously or intranasally to BALB/c mice. Neither subcutaneous immunization
      with SPA emulsified in Freund adjuvant nor intranasal immunization with SPA and
      cholera toxin B subunit elicited any antibody responses to the polysaccharide
      antigen. High serum immunoglobulin M (IgM) and IgG responses to SPA were induced
      by subcutaneous immunization with SPA-bovine serum albumin in Freund adjuvant.
      Serum and salivary IgA responses to SPA in addition to IgM and IgG responses were
      induced by intranasal immunization with the conjugate and cholera toxin B
      subunit. To investigate the functional activity of SPA-specific antibodies, the
      opsonic activity of sera from BALB/c mice immunized with the conjugate was
      assessed by chemiluminescence assay using human polymorphonuclear leukocytes.
      Murine antisera efficiently opsonized A. actinomycetemcomitans serotype b in the
      assay, suggesting that antibodies to SPA of the organism might serve as a
      protective role.

PMID- 9002872
TI  - Differentiation of the serotype b and species-specific antigens of Actinobacillus
      actinobacillus actinomycetemcomitans recognized by monoclonal antibodies.
AB  - The serotype b antigens have been reported to be associated with
      lipopolysaccharide. Using murine monoclonal antibodies specific for either a
      serotype b antigen or the Actinobacillus actinomycetemcomitans species, the
      relationship of the two epitopes to lipopolysaccharide was determined. Both the
      species-specific and serotype b-specific monoclonal antibodies bound to whole
      cells, vesicles and conventionally isolated lipopolysaccharide and polysaccharide
      material derived from A. actinomycetemcomitans culture supernatants. Serotype b
      specific monoclonal antibodies bound to the polysaccharide of acid-hydrolyzed
      lipopolysaccharide. Species-specific monoclonal antibodies bound to both the
      polysaccharide and the lipid A fraction of lipopolysaccharide after acid
      hydrolysis. Polymyxin b partially inhibited the binding of the species-specific
      monoclonal antibodies to lipopolysaccharide and had no effect on the binding of
      the serotype b-specific monoclonal antibodies to lipopolysaccharide.
      Lipopolysaccharide from whole bacteria and polysaccharide material isolated from
      culture supernatants were separated by gel filtration chromatography in
      deoxycholate into fractions that contained serotype b antigen, both serotype b
      and species-specific antigens, or species-specific antigen. SDS-polyacrylamide
      gel electrophoresis and Western blotting analysis of the fractions revealed that
      the serotype b antigen was on a high-molecular-weight polysaccharide material.
      The species-specific antigen was on a ladder of lower-molecular-weight
      polysaccharides identical to the blot pattern of lipopolysaccharide molecules
      separated by polyacrylamide gel electrophoresis and stained with silver stain.
      Chemical analysis of the polysaccharide containing serotype b antigen revealed
      85% ribose, 11% glucose, and no lipid. Chemical content of the species-specific
      antigenic material revealed a composition typical of lipopolysaccharide.
      Immunoelectron microscopy using the species- or serotype b-specific monoclonal
      antibodies confirmed the biochemical and immunological characterization of the
      two antigens, showing that the species-specific epitopes were on the surface of
      the A. actinomycetemcomitans cell membrane and the serotype b-specific epitopes
      on the amorphous material extending from the cell surface. The data indicated
      that the serotype b antigen, detected by the antibody, was separable from
      lipopolysaccharide and was an A. actinomycetemcomitans capsular material. The
      species-specific antigen, being more conserved than the serotype antigen, was on
      all the lipopolysaccharide molecular species.

PMID- 9002875
TI  - Characterization of the immunodominant antigens of Porphyromonas gingivalis 381
      in high-responder patients.
AB  - The immunodominant antigens of Porphyromonas gingivalis 381 whole cells that
      reacted with sera from high-responder patients were examined in this study. Whole
      cells, phenol-water extracted lipopolysaccharide, and fimbriae from P. gingivalis
      381 were analyzed using sera from 14 patients with adult periodontitis, rapidly
      progressive periodontitis or juvenile periodontitis as well as from two healthy
      subjects. Western blot analysis and enzyme-linked immunosorbent assay (ELISA)
      were performed. On Western blots, among many prominent protein bands, a smear was
      observed which was removed after adsorption of the sera with P. gingivalis phenol
      water extracted lipopolysaccharide. Two major protein bands of 43 kDa and 41 kDa
      were found to be prominent even at very high dilutions of sera, the latter of
      which showed the same molecular weight as the fimbrilin band. These two bands
      were resistant to treatment by papain and trypsin. ELISA titers remained high
      after adsorption of the sera with P. gingivalis phenol-water extracted
      lipopolysaccharide. The results of this study suggest that the 43-kDa and the
      fimbrilin (41 kDa) proteins may play an important role as immunodominant antigens
      of P. gingivalis 381.

PMID- 9002874
TI  - Shared antigens of Porphyromonas gingivalis and Bacteroides forsythus.
AB  - Periodontitis in humans is caused by a group of predominantly gram-negative,
      anaerobic bacteria among which Porphyromonas gingivalis and Bacteroides forsythus
      are prominent. A similar group is present and presumably plays a similar role in
      experimental periodontitis in the primate Macaca fascicularis. Nevertheless,
      immunization using a vaccine containing only killed P. gingivalis suppresses the
      progress of experimental periodontitis in M. fascicularis. We investigated the
      hypothesis that gram-negative periodontopathic bacterial may share antigens, and
      immunization with one species may induce antibodies reactive with other gram
      negative species. Using enzyme-linked immunosorbent assay (ELISA), Western and
      dot immunoblots with nonabsorbed and absorbed and immune and preimmune sera we
      show that monkeys immunized with P. gingivalis produce antibodies reactive not
      only with antigens of P. gingivalis but also with those of B. forsythus.
      Similarly, rabbits immunized with P. gingivalis or with B. forsythus produce
      antibodies that react with antigens of both bacteria. Cross-reactive antibodies
      bind to epitopes in lipid A and possibly in core carbohydrate of
      lipopolysaccharide. Using complexes of lipopolysaccharide with polymyxin B,
      bovine serum albumin and apolipoprotein A1 specificity of binding was documented.
      Using sera from monkeys immunized with P. gingivalis, cross-reactivity with
      Actinobacillus actinomycetemcomitans could not be demonstrated by ELI-SA,
      although binding to lipopolysaccharide but not to lipid A was demonstrated by
      Western and dot immunoblots. Antibodies to shared lipopolysaccharide epitopes of
      periodontopathic bacteria may account, at least in part, for the immune
      protection observed in immunized monkeys, and shared epitopes may have potential
      as a vaccine for periodontitis in humans.

PMID- 9002876
TI  - Fc gamma-binding bacteria in periodontal lesions.
AB  - The proportion of bacteria exhibiting surface Fc gamma-binding proteins was
      determined in periodontal pockets of 20 patients diagnosed with periodontal
      disease and in subgingival areas of 20 patients without periodontal lesions.
      Bacterial smears were examined by fluorescence microscopy based on DNA staining
      (Hoechst 33256) and staining of Fc gamma-binding proteins by human biotin
      labelled Fc gamma and Texas red-conjugated streptavidin. Fc gamma-binding
      proteins were observed in all smears from the patients diagnosed with
      periodontitis, and in a majority of the smears high proportions of the bacteria
      were positive for Fc gamma-binding proteins. In contrast, most smears from
      patients without periodontal lesions included low or undetectable proportions of
      bacteria with Fc gamma-binding proteins.

PMID- 9002878
TI  - Effect of antibodies on chemiluminescence and on killing of Streptococcus
      sobrinus by polymorphonuclear leukocytes.
AB  - The effect of a polyclonal antiserum and OMVU10, a monoclonal antibody reactive
      with Antigen B of Streptococcus sobrinus, on the interaction of polymorphonuclear
      leukocytes with S. sobrinus was studied, using chemiluminescence and bacterial
      killing assays. Increased stimulation of neutrophils as measured in the
      chemiluminescence assays was established when S. sobrinus was preincubated with
      polyclonal antiserum or when polyclonal antiserum was added to the reaction
      mixture. Higher counts were measured in comparison to preimmune serum. After 90
      min, 52% of S. sobrinus preincubated with polyclonal antiserum was killed.
      Killing was also increased when polyclonal antiserum was added to the reaction
      mixture in comparison to the controls. No killing was found when bacteria were
      preincubated with OMVU10 or when OMVU10 was added to the reaction mixture in
      comparison to Clone 24, a control antibody.

PMID- 9002877
TI  - Phenotypic profiles of lymphocyte populations isolated from rat major salivary
      glands.
AB  - Marker expression was studied in rat lymphocyte populations isolated from
      parotid, submandibular and sublingual salivary glands. Comparative data were also
      obtained for lacrimal gland and spleen populations. Increased percentages of Thy
      1+ cells were found in salivary gland populations when compared to spleen with
      the highest percentage noted for parotid gland. Thy-1 percentages in parotid
      gland were comparable to those obtained with lacrimal gland. Salivary gland sIg,
      CD5 and CD8 cell percentages were lower than those obtained for lacrimal gland
      and splenic populations. The percentages of CD4-bearing cells in submandibular
      and sublingual gland were lower than those found in parotid gland, lacrimal gland
      and spleen, and the CD4:CD8 ratios in parotid gland most closely approximated
      those in spleen. Increased percentages of Thy-1+ lymphocytes coexpressing sIg and
      CD5 were obtained for all salivary gland cell populations when compared to
      spleen; however, percentages of salivary gland cells bearing these 3 markers were
      lower than noted for lacrimal gland, which contained the highest percentage. With
      respect to adhesion molecules, lymph node homing receptor (LNHR) and Peyer's
      patch homing receptor (PPHR) bearing cells were found in all glandular
      populations with the percentages of LNHR+ exceeding PPHR+ lymphocytes. Homing
      receptor bearing populations were highest in spleen and were present in equal
      proportions. LFA-1 was expressed by all salivary gland cell populations in
      greater percentages than lacrimal gland, but lower than those in spleen. VLA-4
      and CD44 expression was higher in parotid gland and spleen than in submandibular
      and lacrimal gland. These data show that the phenotypes of resident lymphocytes
      in salivary gland tissues differ from lacrimal gland and spleen, as well as each
      other, and indicate that Thy-1+ cells in glandular tissues bear both B and T cell
      markers. The adhesion molecule expression data suggest that these molecules may
      be utilized differently in various glandular tissues, potentially contributing to
      the variation in phenotypic profiles of resident glandular lymphocytes.

PMID- 9002879
TI  - Fimbrial-mediated colonization of murine teeth by Actinomyces naeslundii.
AB  - Groups of mice fed diets high in sucrose or glucose were orally inoculated with
      10(10), 10(9) or 10(8) colony-forming units of one of the following Actinomyces
      naeslundii strains possessing the type 1 (T1+) and/or the type 2 (T2+) fimbriae:
      T14VJ1 (T1+, T2+), 5519 (T1+), 5951 (T2+), and 147 (non-fimbriated). Ninety-six
      hours after inoculation their upper jaws were cultured to look at the
      implantation of each of these strains on the teeth. In mice fed a sucrose diet,
      regardless of the presence or absence of fimbriae, each bacterial strain
      colonized 100% of the mice at the highest inoculation doses of the infecting
      organism. But at a dose of 10(8), T14V-J1 was the only strain which colonized
      100% (12/12) of the mice, 5519 colonized 10/11, 5951 colonized 9/11 and 147
      colonized 7/11. These differences were not statistically significant. When mice
      were fed a high-glucose diet, 100% infection was achieved with strains T14V-J1,
      5519 and 5951 only at the highest dose of 10(10) colony-forming units. Strain 147
      colonized in 8/9 of the mice at that dosage. At lower dosages, no bacterial
      strain implanted in 100% of the mice. In the glucose experiment at a dose of
      10(8), strains expressing the T1 fimbriae implanted significantly better than
      strains without the T1 fimbriae. At a dose of 10(9) colony-forming units, the
      parent strain T14V-J1 implanted significantly better than strains without the T1
      fimbriae. Similarly, strain 5519 (T1+) implanted significantly better than 5951
      and implanted better than 147, although the difference was not significant. These
      results suggest that while the presence of the T1 and T2 fimbriae may confer some
      advantage in the establishment of these organisms in vivo, even the strains
      without fimbriae were able to colonize. Strains T14VJ1 and 5519 were found to
      bind well to hydroxyapatite treated with mouse saliva, while strains 5951 and 147
      did not. Only T2 fimbriated strains T14V-J1 and 5951 exhibited a lactose
      reversible coaggreation with indigenous strains of enterococci that may
      contribute to the elevated levels of colonization of strain 5951 in vivo.

PMID- 9002880
TI  - Polymerase chain reaction detection of 8 putative periodontal pathogens in
      subgingival plaque of gingivitis and advanced periodontitis lesions.
AB  - A 16S rRNA-based polymerase chain reaction (PCR) detection method was used to
      determine the prevalence of Actinobacillus actinomycetemcomitans, Bacteroides
      forsythus, Campylobacter rectus, Eikenella corrodens, Porphyromonas gingivalis,
      Prevotella intermedia. Prevotella nigrescens and Treponema denticola in
      subgingival specimens of 50 advanced periodontitis, 50 adult gingivitis and 50
      pediatric gingivitis subjects. The optimal PCR conditions were determined for
      each study species. Agarose gel electrophoresis of PCR products from each study
      species revealed a single band of the predicted size. Restriction enzyme
      digestion of amplicons confirmed the specificity of the amplification. PCR
      detection limits were in the range of 25-100 cells. No cross-reactivity with
      other oral micro-organisms or nonspecific amplification was observed. The
      prevalence by PCR in advanced periodontitis, adult gingivitis and pediatric
      gingivitis subjects was 30%, 14% and 14% for A. actinomycetemcomitans, 86%, 18%
      and 8% for B. forsythus, 74%, 52% and 78% for C. rectus, 80%, 70% and 66% for E.
      corrodens, 70%, 10% and 14% for P. gingivalis, 58%, 12% and 18% for P.
      intermedia, 52%, 20% and 22% for P. nigrescens, and 54%, 16% and 16% for T.
      denticola, respectively. The prevalence was higher in the advanced periodontitis
      group than in both adult gingivitis and pediatric gingivitis for A.
      actinomycetemcomitans, B. forsythus, P. gingivalis, P. intermedia, P. nigrescens
      and T. denticola at P < 0.01, and for E. corrodens at P < 0.05. The prevalence of
      C. rectus was significantly higher in the advanced periodontitis group than in
      the adult gingivitis group at P < 0.01. Matching results between PCR and culture
      occurred in 28% (B. forsythus) to 71% (A. actinomycetemcomitans) of the samples;
      the major discrepancy occurred in the PCR-positive/culture-negative category.
      Matching results between PCR and DNA probe methods were found in 84% of the
      subjects (B. forsythus) and 70% (P. gingivalis). Odds ratio analysis revealed
      statistically significant positive associations between 17 of the 28 possible
      combinations (P < 0.01). This study demonstrated the utility of a 16S rRNA-based
      PCR detection method for identifying important subgingival microorganisms. The
      results indicated a strong association between the study species and
      periodontitis. Several previously unreported symbiotic relationships were found
      between the 8 species tested.

PMID- 9002881
TI  - Host responses induced by co-infection with Porphyromonas gingivalis and
      Actinobacillus actinomycetemcomitans in a murine model.
AB  - In this study, evidence is presented that mixed infection with the periodontal
      pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans
      results in a synergistic effect in their pathogenicity and in their ability to
      induce humoral and cellular host responses. BALB/c mice were injected
      subcutaneously on the back with P. gingivalis ATCC 53977, A.
      actinomycetemocomitans 75 or a mixture of both bacteria. Samples of blood and
      fluid from abscesses formed at the site of injection (first degree) or distant
      from the injection site were collected for microbiologic analysis. Serum and
      spleens were obtained for evaluation of humoral and cellular responses to P.
      gingivalis and A actinomycetemocomitans. Mice injected with A.
      actinomycetemcomitans had first-degree lesions only, whereas mice injected with
      P. gingivalis and A. actinomycetemcomitans had lesions at first- and second
      degree sites from which both bacterial species were isolated. A serum anti-P.
      gingivalis response was induced in P. gingivalis-injected mice, which was higher
      in mice injected with P. gingivalis and A. actinomycetemcomitans. This pattern
      was not seen in the anti-A, actinomycetemcomitans response. Lymphoproliferative
      responses to phytohemagglutinin, Escherichia coli lipopolysaccharide and P.
      gingivalis of spleen cells from infected mice were decreased, especially
      following co-infection. Furthermore, co-infection of mice resulted in the
      greatest decrease in the number of CD5+, especially CD4+ lymphocytes.

PMID- 9002883
TI  - Controlled-release periodontal chemotherapy: the evolution of antimicrobial
      delivery systems.
AB  - Bacterial plaque contributes to the development and progression of periodontal
      diseases. Therefore, therapeutics designed to stop or slow periodontal
      destruction must limit or eliminate the deleterious effects of plaque. Despite
      the recognized beneficial effects of in-office surgical and nonsurgical
      periodontal therapies and home mechanical plaque control, antimicrobials have
      been used locally, systematically, or in combination to limit plaque activity.
      This article discusses a new, localized antimicrobial delivery method. The
      technique discussed employs an ethylene/vinyl acetate copolymer, containing
      tetracycline hydrochloride. Description of this polymeric fiber, indications for
      its use, placement technique, patient education, the role of auxiliaries, and
      practice management aspects are reviewed. The future potential of sustained
      release local pharmaceutical devices is addressed.

PMID- 9002882
TI  - Detection and prevalence of the tetracycline resistance determinant Tet Q in the
      microbiota associated with adult periodontitis.
AB  - Subgingival plaque samples were collected from 68 patients with a history of
      moderate to severe adult periodontitis and enumerated on Trypticase-soy blood
      agar plates, with and without tetracycline at 4 micrograms/ml. Each different
      colony morphotype was enumerated, and a representative colony was subcultured for
      identification and examined for the tetracycline resistance gene tet(Q) by
      polymerase chain reaction (PCR) amplification and DNA hybridization, using a
      fragment of tetA(Q)2 from Bacteroides fragilis 1126. PCR primers (5'
      GGCTTCTACGACATCTATTA-3' and 5'-CATCAACATTTATCTCTCTG-3') were chosen to amplify a
      755 bp region of tet(Q). The subgingival plaque samples were also tested by PCR.
      Approximately 12% of the total cultivable flora was resistant to tetracycline,
      and the percentage of the tetracycline-resistant cultivable flora with the tet(Q)
      gene varied greatly from one patient to another with a range from 0.0 to 67%.
      Half of the 68 subgingival plaque samples were positive or weakly positive for
      tet(Q) by PCR. Approximately 15% of the 210 isolates subcultured with resistance
      to tetracycline, (> or = 4 micrograms/ml) contained tet(Q), and 60% contained
      tet(M). All of the tet(Q)-resistant isolates were gram-negative anaerobic bacilli
      and included all of the Prevotella and Bacteroides isolates.

PMID- 9002884
TI  - Donor selection, testing, and inactivation of the HIV virus in freeze-dried bone
      allografts.
AB  - This article is a comprehensive review of the safety of currently used freeze
      dried bone allografts. The development of exclusionary criteria for donor
      procurement is discussed along with the steps taken in processing. The processing
      includes harvesting in a sterile manner, repeated washings, immersion in ethanol,
      freezing in liquid nitrogen, freeze-drying, demineralization, and vacuum sealing.
      The statistical data of laboratory testing for the HIV virus is presented, and
      the advantages and disadvantages of the ELISA and the PCR tests are outlined.
      There are four known cases of HIV transmission from bone allograft donors, and
      the circumstances of these four transmissions are discussed. An overview of
      hepatitis and other infectious diseases in bone allografts completes the review.
      The learning objective of this article is to update reader knowledge of measures
      taken to ensure safety in the utilization of DFDB allografts.

PMID- 9002885
TI  - Taking risks.

PMID- 9002887
TI  - Intraoral giant cell lesions: the peripheral and central forms of these entities.
AB  - Giant cell lesions have long been of interest as to their origins and
      pathogenesis. These lesions range from the unusual and rare heritable case of
      Cherubism to the more often encountered peripheral giant cell lesion (granuloma).
      While some giant-cell-containing entities appear as innocuous lesions, others
      form tumorous masses and are locally destructive in nature. Early diagnosis and
      treatment are important to overall patient health and prevention of local tissue
      destruction. The learning objective of this article is to familiarize the
      clinician with the most common of these entities-the peripheral and the central
      giant cell lesions.

PMID- 9002886
TI  - Clinical issues in the prevention of dental-induced endocarditis and prosthetic
      joint infection.
AB  - No issue in medicine or dentistry is the subject of more misunderstanding than
      the prevention of infective endocarditis and late prosthetic joint infections. To
      resolve some of the confusion, national medical groups have published guidelines
      for the prevention of these infections, including the use of antibiotic
      prophylaxis for certain dental procedures and certain at-risk patients. While
      these guidelines are helpful, there still are clinicians who either do not
      recommend antibiotics when indicated or recommend antibiotics without indication.
      An understanding of these issues helps to prevent not only the infections but
      also the adverse antibiotic effects and associated legal problems. The learning
      objective of this article is to educate clinicians on the prevention of dental
      induced endocarditis and prosthetic joint infections.

PMID- 9002888
TI  - Erythroplakia: the dangerous red mucosa.
AB  - Erythroplakia is an uncommon and subtly innocuous change of the oral mucosa, but
      it has very specific and identifiable clinical characteristics, therapies, and
      prognostic features. It is the most dangerous of all the oral cancer precursor
      lesions, and a search for erythroplakia should be a part of every oral soft
      tissue examination in persons aged 35 years and older. No erythroplakia lesions
      should ever be left untreated. Much has been written about the malignant
      potential of oral leukoplakia, but too often the dental profession has ignored
      the more dangerous discoloration, erythroplakia, which carries a much greater
      cancer risk than the white lesions. A clear understanding of this lesion may save
      lives by identifying oral cancers prior to invasion or at an early stage, thereby
      avoiding extensive surgery and spread of the disease to other parts of the body.
      The learning objective of this article is to review and familiarize the reader
      with the terminology, diagnosis, etiology, treatment, and the prognosis of this
      disease.

PMID- 9002889
TI  - Holiday reading.

PMID- 9002890
TI  - Screw-retained versus cement-retained implant-supported prostheses.

PMID- 9002891
TI  - Surgical reconstruction--a prerequisite for long-term implant success: a
      philosophic approach.
AB  - Loss of teeth results in the loss of other tissues. Without adjunctive
      reconstruction of the hard and soft tissues, this loss can impair the
      reconstruction of the dentition using osseointegrated implants. Inadequate
      treatment planning-based on rules derived from anterior implant use in older
      edentulous patients or poor execution of the surgical plan, leading to errors in
      the number, angulation, distribution, and position of implants-can be the
      foundation for future failure. The learning objective of this article is to
      review specific reconstructive measures that may be appropriate in patients with
      special functional, aesthetic, or phonetic demands. The authors suggest that the
      present definition of failure be expanded to include long-term functional,
      aesthetic, and phonetic outcomes.

PMID- 9002892
TI  - Say goodbye to lab bills.

PMID- 9002894
TI  - Single tooth replacement using a one-piece screw-retained restoration.
AB  - This article reviews and illustrates several options available with single tooth
      implant prostheses. For use with internal hex implants, the authors prefer one
      piece screw-retained restorations due to their easy retrievability, absence of
      cement, and remarkable aesthetics. The treatment procedure is outlined from
      presurgical prosthetic planning and surgery to the placement of the final
      prosthesis. The advantages and disadvantages of the technique are reviewed. The
      use of wide or narrow screw access channels is discussed. Selection of torque
      instruments and the proper levels of torque when tightening the screws are
      evaluated. Three clinical cases are presented to illustrate the principles
      reviewed in the text. The learning objective of this article is to provide up-to
      date information on an implant system for screw-retained single tooth
      restorations.

PMID- 9002893
TI  - Guided bone regeneration around exposed implants: a new bioresorbable device and
      bioresorbable membrane pins.
AB  - This article presents the principles and the clinical procedure of utilizing a
      new bioresorbable collagen barrier device, bioresorbable membrane pins, and a new
      bone substitute for bone regeneration around exposed implants. Three cases are
      used to illustrate the clinical procedure. In all three cases, the regeneration
      of bone around the implants was successful, and upon clinical examination the
      newly regenerated material resembled natural bone. Histologic data regarding the
      new bioresorbable collagen barrier itself and the time range in which the
      collagen device functioned as a barrier are still lacking, and the studies are
      currently being conducted. The learning objective of this article is to introduce
      a combination of options available for successful regeneration of bone around the
      implants and avoiding the second-stage surgery.

PMID- 9002896
TI  - The other side.

PMID- 9002895
TI  - Improving aesthetics of implant-supported restorations.
AB  - Osseointegration and adhesion have dramatically improved the treatment
      modalities, and reinstatement of function is now achieved routinely. Aesthetics
      has emerged as a prerequisite to the acceptance of the final result, demanded by
      the patient, and the standards of excellence in prosthetic restorations. This
      article discusses the treatment planning criteria, including tissue augmentation,
      implant selection, and healing abutments; it also suggests a modification in the
      sequence of treatment planning by placing the provisional restoration at second
      stage surgery. This "custom-guided" tissue healing serves to achieve natural
      aesthetics in soft tissues. The learning objective of this article is to
      familiarize the reader with the principles of custom-guided tissue healing and to
      address the aesthetic challenge.

PMID- 9002897
TI  - Protocol for predictable restoration of anterior teeth with composite resins.
AB  - The composite resins have reached a high degree of excellence and are now
      utilized with predictable results in restoring the anterior dentition. This
      article discusses the development of these resins and the histologic and optical
      considerations (polychromatic characteristics, hue, translucency and opacity,
      chroma, value, strength, and polishability). In restorative materials, the use of
      universal or all-purpose restorative resins is considered, ie, materials that
      combine the functional strength necessary for the posterior regions and the high
      gloss polishability necessary to emulate enamel in the anterior. The restorative
      sequence of cervical, middle, and incisal thirds describes the materials best
      suited for each third, along with aids to create the intricate refinement of hue,
      chroma, and value. The learning objective of this article is to review the
      principles involved in these restorations and to provide a protocol for their
      clinical implementation.

PMID- 9002898
TI  - Restoration of primary molars using a new "compomer" material.
AB  - The primary advantages of glass ionomer restorative materials are adhesion to
      tooth structure and release of fluoride. A new material has been recently
      introduced for the restoration of cervical lesions and Class I defects in primary
      teeth. The material combines the properties of glass ionomers with the advantages
      of a single-component, light-activated composite resin and is known as a
      "compomer". This new material contains two resins, instead of the acidic polymers
      found in conventional glass ionomers. The restorative material releases fluoride
      and can be infected directly into the cavity. With its own bonding agent, the
      compomer offers a simple and relatively rapid technique. The learning objective
      of this paper is to describe the utilization of the new restorative material in
      conjunction with a bonding agent to restore conservative cavity preparations in
      primary molars. Two clinical cases are used to illustrate the presentation.

PMID- 9002899
TI  - Balancing your personal and dental life.

PMID- 9002900
TI  - High velocity air microabrasion for conservative tooth preparation: the principle
      and the clinical procedure.
AB  - Various technologies within the dental armamentarium are applied to achieve the
      precise tooth preparations required for the different types of restorations. This
      article reintroduces the air microabrasion technique, which was first presented
      in 1945. The popular use of this technique had been postponed, pending the
      decrease in cost and development of compatible restorative materials to repair
      the tooth structure. With increased patient demand for less invasive preparation
      techniques and the decrease of the equipment cost, the use of air microbrasion
      for tooth preparation has been recognized. The history of the technology, its
      function, indications, advantages, and limitations are discussed, and a step-by
      step clinical procedure is presented. The learning objective of this article is
      to familiarize the readers with this preparation procedure, enhancing the
      knowledge of preparation options.

PMID- 9002901
TI  - Localized prepubertal periodontitis--nonsurgical treatment of an adolescent
      patient: a case report.
AB  - The treatment of localized juvenile periodontitis has been previously described
      in the literature, utilizing primarily a long-term (2 to 6 week) antibiotic
      regimen, notably tetracycline. This case report of juvenile periodontitis with
      extensive bone loss describes a short-term treatment (8 days), using a
      combination of two antibiotics and mechanical debridement. Clinical treatment
      included instruction of proper oral hygiene techniques. Initial scaling and root
      planing were performed to remove supragingival and subgingival accretions,
      followed by 2-month maintenance recalls. Pre- and postoperative radiographs,
      taken one year after the treatment, are used to document the evidence of natural
      bone regeneration. The learning objective of this article is to present an
      effective method of treatment-a debridement/antibiotic combination, followed by
      bone regeneration.

PMID- 9002902
TI  - Vital bleaching for aesthetic improvement.
AB  - Vital bleaching is one of the least invasive, most conservative, and most cost
      effective procedures to dramatically improve the aesthetic appearance of a
      patient's smile and self-confidence. Bleaching began as an in-office procedure
      and required multiple visits. With the arrival of dentist-monitored at-home
      procedures, bleaching has become widely known and used. This presentation
      evaluates the advantages of the higher viscosity adhesive formulation bleaching
      materials, which prevent dehydration and reduce the subsequent color change upon
      rehydration.

PMID- 9002904
TI  - Solving posterior composite sensitivity.

PMID- 9002903
TI  - Free-hand composite resin restorations: a key to anterior aesthetics.
AB  - The success of free-hand bonding in anterior teeth depends on a harmonious
      integration of various elements, including a thorough understanding of natural
      function, aesthetics, characteristics of current materials, and restorative
      techniques. The selection of composite brands which offer a variety of shades and
      provide several opacities is mandatory. By utilizing an anatomic stratification
      with successive layers of dentin, enamel, and incisal composite, a natural
      appearing aesthetic result can be achieved in a relatively simple and predictable
      manner. Attentive use of finishing methods is still necessary for surface quality
      and natural appearance of the final restoration. Direct composite bonding remains
      an adequate therapeutic modality in traditional Class III to Class V and
      localized cosmetic restorations. It can satisfy most aesthetic demands, and it
      offers an affordable alternative to more invasive procedures, such as veneers and
      crowns. The learning objective of this article is to review anterior free-hand
      bonding utilizing composite restorative materials.

PMID- 9002905
TI  - Modified porcelain-fused-to-metal restorations and porcelain laminates for
      anterior aesthetics.
AB  - Since the late 1950s, porcelain-fused-to-metal (PFM) restorations have remained a
      standard modality for rehabilitation of anterior dentition. This article
      discusses recent modifications to improve aesthetics, using clinical cases to
      present the multifaceted potential of this type of restoration. Color and contour
      are discussed. The use of a combination of laminate veneers and PFM restorations
      is presented in cases where the crown restorations of the adjacent teeth are not
      necessary, but color and contour require enhancement to achieve an aesthetic
      result. The learning objective of this article is to review the utilization of
      the improved porcelain laminates and the modified PFM crowns.

PMID- 9002906
TI  - Neutralizing negative notoriety.

PMID- 9002907
TI  - Anterior maxillary aesthetics utilizing all-ceramic restorations.
AB  - The use of all-ceramic systems has increased significantly during recent years,
      due to the improved strength and the introduction of a new generation of dental
      adhesive agents and resin cements. Both factors permit reliable and predictable
      results in single jacket crown restorations in the maxillary anterior region. Due
      to their natural appearance, the all-ceramic materials, especially the glass
      ceramics, blend harmoniously with the oral environment and are particularly
      appreciated where aesthetics is a priority. The learning objective of this
      article is to demonstrate a routine utilization of all-ceramic systems in the
      maxillary anterior region, preceded by a proper case selection. Two clinical
      cases are used to illustrate the preparation procedure, the importance of well
      integrated provisional restorations, and the accuracy in transferring provisional
      information onto the final jacket crowns.

PMID- 9002908
TI  - Aesthetic treatment of discoloration of nonvital teeth.
AB  - Attempts to treat discoloration in nonvital teeth were first reported a century
      ago. This article discusses two potential causes of nonvital tooth discoloration
      trauma and endodontic treatment-along with a step-by-step clinical procedure for
      treatment of the discoloration. In trauma, hemoglobin is released into the
      tissues; iron oxides, formed by oxygen and iron in hemoglobin, cause
      discoloration and swelling that infringes on pulp space, forcing the pulp to
      recede with a potential loss of tooth vitality. After endodontic treatment,
      either hemorrhaging, materials used, or incomplete removal and breakdown of
      necrotic tissue may cause staining. The learning objective of this article is to
      review the causes and the prevention/treatment of discoloration in nonvital
      teeth.

PMID- 9002909
TI  - Surgical reinstatement of aesthetics in the maxillary anterior region: a case
      report.
AB  - The maxillary anterior region is frequently treated for aesthetic enhancement.
      This article presents the case of a patient who had undergone surgery for
      treatment of a tumor of the hypophysis involving intraoral access to the sella
      turcica. The treatment had caused the formation of severe gingival recession on
      the buccal surface of the maxillary anterior teeth. A variety of surgical
      techniques were considered for covering the exposed root surfaces. The surgical
      site was analyzed, and the response of the periodontal tissue to the treatment
      was anticipated. The bilaminar method, utilizing a subpedicle connective tissue
      graft (SCTG), was selected. The learning objective of this case presentation is
      to demonstrate that when the appropriate treatment procedure is selected,
      restoration of function and aesthetics can be achieved even in the most advanced
      cases.

PMID- 9002910
TI  - The randomized clinical trial as a powerful means for understanding treatment
      efficacy.
AB  - The comparison of technologies, ie, alternative ways to accomplish the same aim,
      is inherently difficult. In orthodontics, technology covers a wide spectrum of
      areas: variations in treatment approach, appliances, wires, diagnostic
      procedures, and patient management techniques. Clinical trial methodology has
      been developed to minimize the effect of bias and to provide more objective
      answers to questions of comparative efficacy and benefits of particular
      treatments or procedures. The randomized controlled clinical trial (RCT) is now
      generally considered the strongest research design for the comparison of
      treatments. This report reviews four issues that should be addressed in planning
      an RCT: defining the study cohort, selecting the treatment allocation technique,
      estimating sample size, and performing the trial.

PMID- 9002911
TI  - Decision analysis to optimize the outcomes for Class II Division 1 orthodontic
      treatment.
AB  - Selection of the treatment method of choice in orthodontics is usually a question
      of the clinician's personal preference and is generally based on subjective
      criteria. Orthodontic treatment of malocclusions is unlike treatment of a disease
      and hence terms such as success and failure are relative and undefined. Ideally,
      both patients and providers should be able to arrive at treatment decisions that
      have the greatest potential for optimum outcomes at minimal cost and risks. This
      article applies the method of decision analysis to demonstrate how policy choices
      between "one-stage" or "two-stage" treatment of Class II Division 1 malocclusions
      for children between 11 and 14 years old can be based on objective criteria. A
      decision tree was designed to yield the value of payoffs, or outcomes, at each of
      the possible terminal nodes, and the probability of each payoff. Both positive
      (ie, improvement in malocclusion) and negative (ie, extraction of teeth and long
      treatment duration) attributes of outcomes were considered, and numerical values,
      or "utilities," were assigned to each outcome. For this model, one-stage
      nonextraction treatment yields the highest probability of maximum benefit.
      Further applications of decision analysis to resolve clinical uncertainties in
      orthodontics are discussed.

PMID- 9002912
TI  - Temporomandibular disorders after early Class II treatment with bionators and
      headgears: results from a randomized controlled trial.
AB  - Symptoms and signs of temporomandibular disorders were assessed in children
      enrolled in a randomized controlled trial of early treatment for Class II
      malocclusion. Children (mean age of 9.8 years) were assigned to a treatment
      protocol (bionator, n = 60; observation, n = 60; headgear/bite plane, n = 71)
      using randomized block stratification. Temporomandibular joint (TMJ) sounds,
      joint capsule pain to palpation, and muscle pain to palpation were scored as
      binary responses (present/absent in a subject). Determinations were made by
      blinded, calibrated examiners initially (DC1) and after a Class I molar
      correction was achieved or 2 years had elapsed (DC3). Univariate relationships
      among explanatory factors (group assignment, gender, age, time interval between
      DC1 and DC3, Class II severity, mandibular plane angle, preparatory treatment,
      whether Class I molar relation was achieved) and binary responses were explored
      using Chi square tables and ANOVA methods. Logistic regression modeled the
      relationship between binary responses and the explanatory variables. At DC1, the
      3 groups were equivalent in the explanatory variables (P > .05). Subjects with a
      TMJ sound, joint pain, and/or muscle pain at follow-up were more likely those who
      had the sign at baseline (P < .01). Early treatment with bionators and
      headgear/bite planes did not place healthy children without these signs at risk
      for developing these signs. Only increasing age (for the development of sounds, P
      < .04) and failure to achieve a Class I molar relation (for development of muscle
      pain, P < .04) placed sign-free children at greater risk. Subjects with TMJ pain
      at baseline were 7 times more likely to have pain at follow-up if they had been
      treated with a headgear/bite plane or observed than if they had been treated with
      a bionator (P = .007). We conclude that an immediate benefit or risk for children
      receiving early Class II treatment with bionators and headgear/bite planes with
      respect to temporomandibular joint function does not exist with the prospect that
      Class II children with TMJ capsule pain may benefit from bionator therapy.

PMID- 9002914
TI  - Maxillary adaptation to expansion in the mixed dentition.
AB  - This study presents the findings of 162 patients who underwent rapid maxillary
      expansion during the early mixed dentition. Maxillary changes were evaluated
      through the analysis of serial dental casts. Arch dimensions were measured pre
      expansion, immediately post-expansion, and at yearly intervals until the eruption
      of the first premolars. The expansion was effected with an acrylic rapid
      maxillary expansion appliance bonded to the posterior teeth for 5 to 6 months. A
      simple retention protocol was used post-expansion. The average increase in
      transpalatal width was 5 to 6 mm. During the post-expansion period, most of the
      arch width increases were maintained. For example, 90.5% of the original
      expansion at the first permanent molars remained after the first year, with
      slightly less overall expansion (80.4%) evident at the end of the observation
      period (2.4 years postexpansion). Maxillary dental arches that initially were
      narrow tended to retain a greater percentage of the achieved expansion than those
      with initially wider arch dimensions. In addition, maxillae with initially more
      lingually-inclined molars tended to retain more expansion than maxillae with
      initially more facially-inclined molars. Palatal vault height decreased very
      slightly during treatment, but returned to pretreatment values one year after
      expansion and increased slightly during subsequent time intervals. The results of
      this study indicate that the majority of increased arch dimensions in patients
      produced by early orthopedic expansion of the maxilla are maintained at the end
      of the transitional dentition.

PMID- 9002913
TI  - Monitoring growth during orthodontic treatment.
AB  - The relationship between somatic growth and orthodontic treatment has been
      limited to the evaluation of body height and skeletal age relative to
      craniofacial development. The aim of this study was to evaluate the correlation
      of anthropometric and biochemical measures of general growth with facial and
      occlusal changes during the early treatment of Class II Division 1 malocclusion.
      Findings are reported from 46 children, ages 7.20 to 12.85 years (skeletal ages,
      5.75 to 12.75 years), who are enrolled in a prospective clinical trial. Body and
      knee heights were measured monthly, with a Holtain stadiometer and a Knee Height
      Measuring Device, respectively. Every three months, serum levels were measured of
      the hormone dehydroepiandrosterone sulfate (DHEAS), an androgen associated with
      growth in midchildhood, and osteocalcin, an indicator of bone turnover.
      Significant correlations existed between knee height and various occlusal
      measurements, but mandibular length was not significantly correlated with knee
      height and DHEAS levels. Knee height correlated significantly (P < .05) with
      DHEAS and osteocalcin only in 46% and 37% of the children, respectively. The
      results indicate that the evaluated biochemical measures, at the time intervals
      considered, may not increase the accuracy of growth depiction by physical
      measures alone (height and skeletal maturation).

PMID- 9002915
TI  - Leeway space and the resolution of crowding in the mixed dentition.
AB  - The leeway space provides adequate space to resolve crowding that is present in
      the mixed dentition in the majority of individuals. This space can be maintained
      by preserving arch length with a lingual arch as the primary teeth begin to
      exfoliate, unless conditions such as the premature loss of a primary canine
      require earlier intervention. A lip bumper can also be inserted after the
      eruption of the first premolars to preserve arch length.

PMID- 9002916
TI  - Odor identification in young and elderly African-Americans and Caucasians.
AB  - Olfactory function is affected by age and gender. However, there are few data on
      smell function in various racial/cultural groups, in particular, in different
      aged African-Americans. Therefore, this study sought to determine if there is a
      relationship among age, gender, and race for smell identification. Sixty healthy
      African-Americans and 60 Caucasians between the ages of 20-40 and 60-80 years
      were administered the University of Pennsylvania Smell Identification Test
      (UPSIT). Older persons, regardless of race, had lower UPSIT scores, were more
      likely to be microsmic and anosmic, and had increased chemosensory complaints.
      Smell performance among females was better compared with males. Overall, African
      Americans had lower UPSIT scores and age- and gender-adjusted percentile rank
      scores compared with Caucasians, but these differences were significant only
      among younger subjects. In addition, both young and old African-Americans had no
      smell complaints. The results from this study suggest that age, gender, and race
      have an influence on smell identification.

PMID- 9002917
TI  - Oral epidermolysis bullosa in adults.
AB  - A rare case of epidermolysis bullosa in an adult is reported and the English
      language dental literature of the last 20 years is reviewed. Special dental
      management is suggested. Early detection because of potential malignant
      transformation is discussed.

PMID- 9002918
TI  - Treatment of a patient with hereditary gingival fibromatosis: a case report.
AB  - A case of hereditary gingival fibromatosis is presented. Treatment consisted of
      apically positioned flap surgery and CO2 laser evaporation. Diagnostic and
      treatment issues are discussed.

PMID- 9002919
TI  - A pilot study comparing three salivary collection methods in an adult population
      with salivary gland hypofunction.
AB  - The purpose of this pilot study was to compare the reliability of three
      collection methods (draining, chewing of gum base, and the Saxon test) for whole
      saliva using a sample of middle-aged and older ambulatory adults (n = 18) with
      proven salivary gland hypofunction. The results demonstrated high reliability (r
      values ranging from 0.91 to 0.80, p < 0.001) for all three methods. MANOVA
      analysis revealed significant (p < 0.001) differences in flow rates among the
      draining, chewing-stimulated, and Saxon methods.

PMID- 9002920
TI  - Chlorhexidine swabbing applications under various conditions of use in preventive
      oral care for persons with disabilities.
AB  - A sample of 44 adults with severe disabilities completed a randomized single
      blind cross-over study testing chlorhexidine swabbing under various conditions:
      with/without prior dental prophylaxis, reduced frequency of application (2 vs. 5
      times per week), and prolonged use (42 weeks). All subjects received therapeutic
      doses of 10 mL 0.12% chlorhexidine gluconate (Peridex, Procter & Gamble) and 10
      mL 0.05% NaF applied with a Toothette (Sage Products). Clinical effectiveness of
      chlorhexidine swabbing compared with placebo was previously reported. In the
      present study, while initial benefits were observed to be independent of dental
      prophylaxis, significant reductions in periodontal scores were sustained by a
      combination of dental prophylaxis and swabbing protocol, at reduced frequency of
      application and over prolonged time. High levels of acceptance and compliance by
      subjects/caregivers were maintained. Subjects/caregivers reported improvements in
      dental health as well as in attitude, quality of life, and smile. Chlorhexidine
      swabbing at maintenance frequency, combined with periodic dental prophylaxis, may
      offer an effective and pragmatic long-term preventive regimen for persons with
      disabilities.

PMID- 9002921
TI  - Protection of patient's rights, or supervised neglect?

PMID- 9002922
TI  - Compliance with fluoride gel use in irradiated patients.
AB  - Patients who undergo radiation therapy that includes the salivary glands
      frequently experience severe xerostomia. The standard of care for these patients
      who have natural teeth has become daily application of fluoride by means of
      custom-fabricated carriers. The purpose of this study was to determine patient
      compliance with fluoride gel application using carriers. Using a structured
      verbal questionnaire, we interviewed 76 patients who had completed radiation
      therapy for head and neck cancer. Thirty of these patients were seen regularly in
      the dental clinic of the Cancer Agency (group 1); the remaining 46 were not seen
      on a regular basis (group 2). Overall, 43% of patients reported using fluoride
      gel regularly (once a day). In group 1, 67% of patients used fluoride regularly,
      as did 28% of patients in group 2 (p = 0.001). There were no significant
      differences between the groups in frequency of toothbrushing and use of dental
      floss. Compliance with the use of fluoride in carriers was not associated with
      differences in other oral care measures in the two groups, which suggests that
      fluoride application in carriers achieves limited compliance in relation to daily
      oral health care measures. Regular follow-up of patients after radiation therapy
      is needed to assess their need for, and compliance with, daily fluoride
      application.

PMID- 9002923
TI  - Panoramic radiography: the differential diagnosis of carotid artery atheromas.
AB  - Cervical carotid artery atherosclerosis, a major cause of stroke (cerebrovascular
      accident, CVA), commonly occurs in older individuals with a history of
      hypertension and smoking. These atheromatous plaques, when calcified, may be
      imaged on conventional panoramic dental radiographs. Dentists caring for "at-risk
      patients" must be able to identify these lesions and to differentiate them from
      anatomical and other pathological radiopacities frequently observed in the
      carotid artery territory. Prompt referral of these individuals to a physician may
      preclude a stroke.

PMID- 9002925
TI  - Dental health of children with cerebral palsy following sialodochoplasty.
AB  - Drooling occurs commonly in children with cerebral palsy (CP). Surgical
      procedures, known as slalodochoplasties, are often performed for the control of
      drooling. These include major salivary gland excision, parasympathetic nerve
      section, duct ligation, and duct re-routing. Alterations in saliva amount, flow,
      and consistency occur following sialodochoplasty, and the resultant effect on
      dental homeostasis requires further investigation. This controlled study
      investigated 19 children with CP following sialodochoplasty (surgery group) and
      75 children with CP treated nonsurgically (control group) who attended our
      hospital. Dental caries experience-including dmft, DMFT, and partial DMFS scores
      of mandibular incisors and canines only-plaque index, and enamel developmental
      defects index were recorded. Saliva buffering capacity and bacterial counts were
      assessed. The surgical group (median DMFT = 5.00) had significantly more dental
      caries when compared with the control group (median DMFT = 0.00), Wilcoxon Signed
      rank Test, P < 0.0001. This study has shown that children with CP following
      sialodochoplasty have increased risk of dental caries when compared with those
      treated nonsurgically for drooling. Although no caries predictors were
      identified, alterations to the caries-protective role of saliva are considered
      the likely cause. Children who undergo this procedure should receive intensive
      pre- and postsurgical preventive dental therapy.

PMID- 9002924
TI  - An efficacious oral health care protocol for immunocompromised patients.
AB  - A twice-weekly oral and perioral examination was provided to 120 patients
      receiving antineoplastic therapy. Sixty patients were monitored while following
      the traditional hospital oral care protocol (chlorhexidine, hydrogen peroxide,
      sodium bicarbonate, thymol glycol, benzocaine mouthrinse, and nystatin). The
      mouth care protocol was then changed (experimental protocol = chlorhexidine,
      benzocaine lozenges, amphotericin B lozenges), and patients were monitored until
      the sample size matched that of the hospital mouth care regime. There was a
      statistically significant reduction in oral complications upon introduction and
      maintenance of the experimental protocol.

PMID- 9002926
TI  - Outpatient dental services for individuals with mental illness: a program
      description.
AB  - This paper describes a state-funded program providing dental services for
      community-based mentally ill clients. Contrasts between outpatient services for
      persons with mental illness and similar programs serving the mentally retarded
      population are emphasized. Implications of client eligibility, communication, and
      compliance issues relative to limitations of care are discussed. Suggestions for
      improving similar programs are provided.

PMID- 9002927
TI  - Medically necessary oral care, Medicare, Medicaid, managed care, and mayhem.

PMID- 9002928
TI  - Early diagnosis of oral cancer.

PMID- 9002929
TI  - The costs and consequences of neglected medically necessary oral care.
AB  - Oral diseases and conditions may adversely affect general health, and certain
      medical conditions may have a negative effect on oral health. However, little
      attention has been given to assessing the economic costs and consequences
      associated with care that is a direct result of, or has a direct impact on, an
      underlying medical condition and/or its resulting therapy. The costs can be
      significant for patients; their families; third-party payers such as insurance
      companies, Medicare, and Medicaid; and society. The health consequences of such
      conditions may dramatically affect function, morbidity, quality of life, and
      survival. This paper reviews one possible approach for identifying and measuring
      the costs and consequences associated with medically necessary oral health care
      and presents a framework for evaluating medically necessary oral health care. The
      paper also describes the cost components of care and the dimensions of health
      consequences. Finally, an example illustrates this approach. The summary
      information presented here is meant to offer concepts and ideas important in
      assessing the costs and health consequences associated with medically necessary
      oral health care. Individuals interested in a more detailed discussion of
      economic evaluation of health care programs and outcomes assessment are referred
      elsewhere. 10-23

PMID- 9002930
TI  - What is currently available in terms of medically necessary oral care?

PMID- 9002931
TI  - National Alliance for Oral Health Consensus Conference on Medically Necessary
      Oral Health Care: Legal issues.
AB  - This paper examines medical malpractice law as it applies to medically necessary
      oral health care. The basic legal concepts and reported cases involving medically
      necessary oral health care are reviewed. It is concluded that dental
      professionals and consumer advocates must advance their educational and
      legislative advocacy efforts so that health professional colleagues and the
      public will become aware of the importance of these services and insurers will
      routinely include coverage of medically necessary oral health care in their
      medical and dental policies. While failure to provide medically necessary oral
      health care can be violative of patient rights and legally actionable, medical
      malpractice litigation should always be the behavior modifier of last resort.

PMID- 9002933
TI  - Microwave processing of acrylic resin.

PMID- 9002932
TI  - Consensus conference on medically necessary oral health care. National Alliance
      for Oral Health, Chicago, Illinois April 29-30, 1995. Final recommendations.

PMID- 9002934
TI  - New technique for surface flattening in facial reconstruction.

PMID- 9002935
TI  - Defined benefit plans still can benefit your business.

PMID- 9002936
TI  - Activating mutations in cytokine receptors: implications for receptor function
      and role in disease.

PMID- 9002937
TI  - Fc gamma RIIA H/R 131 polymorphism, subclass-specific IgG anti-heparin/platelet
      factor 4 antibodies and clinical course in patients with heparin-induced
      thrombocytopenia and thrombosis.
AB  - The explanation why only a subset of patients with heparin-induced
      thrombocytopenia (HIT) develop clinically apparent thromboses (HITT) remains
      uncertain. It has been proposed that platelet activation induced by cross-linking
      of Fc gamma RIIA by anti-heparin/platelet factor 4 (PF4) antibodies is central to
      the pathogenesis of thrombosis. The observation that a common functional
      polymorphism of Fc gamma RIIA, involving either an arginine (R) or histidine (H)
      at amino acid 131, may underlie disease susceptibility prompted us to investigate
      the prevalence of receptor isoforms in patients with HIT and HITT. Furthermore,
      because these isoforms reportedly differ in their avidity for immune complexes
      containing human IgG2, we also analyzed sera from patients with HIT and HITT for
      the prevalence of various subclass-specific IgG anti-heparin/PF4 antibodies. No
      difference in the allele frequency of Fc gamma RIIA-H131 or R131 was identified
      among 13 patients with HIT or 23 with HITT compared with 102 controls (chi 2 =
      1.21, P = .8). Furthermore, although most patients had IgG2 antibodies (62%),
      IgG, was the predominant subclass in 30 of the 34 patients with IgG anti
      heparin/PF4 antibodies and in 12 was the exclusive subclass found. Also, there
      was no association between the concordance of IgG2 anti-heparin/ PF4 antibodies
      and the expression of Fc gamma RIIA-H131 in patients with HITT compared with
      patients with thrombocytopenia alone. These results make it unlikely that the Fc
      gamma RIIA-H131 isoform or IgG2 anti-heparin/PF4 antibodies are required to
      develop HITT, suggesting that factors in addition to cross-linking of Fc gamma
      RIIA receptors contribute to the pathogenesis of thrombosis in patients with
      heparin-dependent antiplatelet: antibodies.

PMID- 9002938
TI  - Altered myeloid development and acute leukemia in transgenic mice expressing PML
      RAR alpha under control of cathepsin G regulatory sequences.
AB  - Acute promyelocytic leukemia (APML) is characterized by abnormal myeloid
      development, resulting an accumulation of leukemic promyelocytes that are often
      highly sensitive to retinoic acid. A balanced t(15;17) (q22;q21) reciprocal
      chromosomal translocation is found in approximately 90% of APML patients; this
      translocation fuses the PML gene on chromosome 15 to the retinoic acid receptor
      alpha (RAR alpha) gene on chromosome 17, creating two novel fusion genes, PML-RAR
      alpha and RAR alpha-PML. The PML-RAR alpha fusion gene product, which is
      expressed in virtually all patients with t(15;17), is thought to play a direct
      role in the pathogenesis of APML. To determine whether PML-RAR alpha is
      sufficient to cause APML in an animal model, we used the promyelocyte-specific
      targeting sequences of the human cathepsin G (hCG) gene to direct the expression
      of a PML-RAR alpha cDNA to the early myeloid cells of transgenic mice. Mice
      expressing the hCG-PML-RAR alpha transgene were found to have altered myeloid
      development that was characterized by increased percentages of immature and
      mature myeloid cells in the peripheral blood, bone marrow, and spleen. In
      addition, approximately 30% of transgene-expressing mice eventually developed
      acute myeloid leukemia after a long latent period. The splenic promyelocytes of
      mice with both the nonleukemic and leukemic phenotypes responded to all-trans
      retinoic acid (ATRA) treatment, which caused apoptosis of myeloid precursors.
      Although low-level expression of the hCG-PML-RAR alpha transgene is not
      sufficient to directly cause acute myeloid leukemia in mice, its expression
      alters myeloid development, resulting in an accumulation of myeloid precursors
      that may be susceptible to cooperative transforming events.

PMID- 9002939
TI  - Differential activation of the tyrosine kinases ZAP-70 and Syk after Fc gamma RI
      stimulation.
AB  - Engagement of the high-affinity IgG Fc receptor (Fc gamma RI) activates a signal
      transduction pathway involving tyrosine phosphorylation of associated kinases. We
      compared the activation of the related protein tyrosine kinases (PTKs), Syk and
      ZAP-70, in Fc gamma RI-mediated signaling. Cross-linking of the Fc gamma RI
      multimeric receptor in monocytic cells results in tyrosine phosphorylation of the
      Fc epsilon RI gamma subunit and association of Syk with this complex. We stably
      introduced ZAP-70 via a retroviral vector into two monocytic cell lines, U937 and
      THP-1, which normally do not express ZAP-70. Neither Syk nor MAP kinase
      activation was affected by the presence of ZAP-70. Although transduced ZAP-70 had
      in vitro kinase activity and associated with Fc epsilon RI gamma after receptor
      aggregation, it was not tyrosine phosphorylated. In contrast, both ZAP-70 and Syk
      were phosphorylated in a T-cell line in which their respective levels of
      expression were similar to those detected in U937/ZAP-70 cells. Therefore, these
      results suggest that requirements for Syk and ZAP-70 phosphorylation are distinct
      in a monocytic cell context.

PMID- 9002940
TI  - A single genetic origin for a common Caucasian risk factor for venous thrombosis.
AB  - A common genetic risk factor for venous thrombosis among Caucasoid subpopulations
      is a polymorphism, nt G1691A, in blood coagulation factor V that replaces Arg506
      with Gln and imparts resistance of factor Va to the anticoagulant, activated
      protein C. Haplotype analyses using six dimorphic sites in the factor V gene for
      117 Caucasian subjects of Jewish, Arab, Austrian, and French origin who were
      homozygous for nt A1691 compared with 167 controls (nt G1691) support a single
      origin for this polymorphism. The nt G1691A mutation is estimated to have arisen
      circa 21,000 to 34,000 years ago, ie, after the evolutionary divergence of
      Africans from non-Africans and of Caucasoid from Mongoloid subpopulations.

PMID- 9002941
TI  - A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in
      patients with refractory Hodgkin's lymphoma.
AB  - The anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, was used in a phase I dose
      escalation trial in patients with refractory Hodgkin's lymphoma. The IT was
      constructed by linking the monoclonal antibody RFT5 via a sterically hindered
      disulfide linker to deglycosylated ricin-A. All patients in this trial were
      heavily pretreated with a mean of 5 (range, 2 to 8) different prior therapies,
      including autologous bone marrow transplantation in 8 of 15. The mean age was 29
      years (range, 19 to 34 years). Thirteen of 15 patients had advanced disease
      (stage IV) with massive tumor burdens and 6 of 15 had B symptoms. The IT was
      administered intravenously over 4 hours on days 1, 3, 5, and 7 for total doses
      per cycle of 5, 10, 15, or 20 mg/m2. Patients received one to four cycles of
      treatment. The peak serum concentration of intact IT varied from 0.2 to 9.7
      micrograms/mL. The serum half life (T1/2) of the IT ranged from 4.0 to 10.5 hours
      (mean, 6.1 hours). Side effects were related to vascular leak syndrome (VLS), ie,
      decreases in serum albumin, edema, weight gain, hypotension, tachycardia,
      myalgia, and weakness. Two patients had a National Cancer Institute (NCI) grade 2
      allergic reaction with generalized urticaria and mild bronchospasm. At 15 mg/m2,
      1 patient experienced a grade 3 myalgia. All 3 patients receiving 20 mg/m2
      experienced NCI grade 3 toxicities (edema, nausea, dyspnea or tachycardia) and 1
      patient had NCI grade 4 myalgia. Thus, the maximal tolerated dose was 15 mg/m2.
      Seven of 15 patients made human antiricin antibodies (> or = 1.0 microgram/mL)
      and 6 of 15 developed human antimouse antibodies (> or = 1.0 microgram/mL).
      Clinical response included 2 partial remissions, 1 minor response, 3 stable
      diseases, and 9 progressive diseases. As has been predicted from the preclinical
      tests, these data seem to indicate clinical efficacy of this new IT in heavily
      pretreated Hodgkin's patients, thus warranting further clinical investigation.

PMID- 9002942
TI  - Avoidance of allogeneic blood transfusions by treatment with epoetin beta
      (recombinant human erythropoietin) in patients undergoing open-heart surgery.
AB  - In a double-blind, randomized, placebo-controlled trial, we evaluated the ability
      of epoetin beta (recombinant human erythropoietin) to avoid allogeneic blood
      transfusions (ABT) and the associated risks in patients undergoing primary
      elective open-heart surgery and in whom autologous blood donation (ABD) was
      contraindicated. Seventy-six patients overall were enrolled onto the trial and
      were randomly assigned to the two treatment groups, 5 x 500 U/kg body weight (BW)
      epoetin beta or placebo intravenously over 14 days preoperatively. All patients
      received 300 mg Fe2+ orally per day during the treatment period. Preoperatively,
      the mean hemoglobin increase was 1.50 g/dL greater in epoetin beta patients than
      in placebo patients (95% confidence interval, 1.10 to 1.90 g/dL), allowing a
      rapid return to the baseline value by the seventh postoperative day in most
      epoetin beta patients. The mean volume of blood collected by intraoperative
      isovolemic hemodilution was 562 mL (red blood cell mass, 274 mL) in the epoetin
      beta group and 218 mL (red blood cell mass, 94 mL) in the placebo group,
      respectively. Only four patients (11%) in the epoetin beta group received an ABT,
      compared with 19 (53%) in the placebo group (P = .0003). Epoetin beta was most
      useful in patients with a perioperative blood loss greater than 750 mL, in those
      with a baseline hematocrit value less than 0.42, and in those aged > or = 60
      years. The iron supplementation proved adequate despite the fact that a
      significant decrease in ferritin (median, 48.1%) and transferrin saturation
      (median, 40.5%) was observed in epoetin beta patients preoperatively. No
      influence of epoetin beta therapy on blood pressure, laboratory safety variables,
      or the frequency of specific adverse events was observed. Intravenous epoetin
      beta treatment of 5 x 500 U/kg BW in combination with 300 mg Fe2+ orally per day
      administered over 14 days preoperatively is an adequate therapy for increasing
      mean hemoglobin levels by approximately 1.50 g/dL and reducing the allogeneic
      blood requirement in patients undergoing elective open-heart surgery and in whom
      ABD is contraindicated.

PMID- 9002943
TI  - 3'-Azido 3'-deoxythymidine + methotrexate as a novel antineoplastic combination
      in the treatment of human immunodeficiency virus-related non-Hodgkin's lymphomas.
AB  - We have previously reported that 3'-azido 3'-deoxythymidine (AZT) can possess a
      significant antineoplastic activity when combined with drugs that disrupt de novo
      thymidylate synthesis, such as 5-fluorouracil and methotrexate (MTX). The aim of
      the present study was to evaluate the efficacy and the tolerance of the
      combination AZT + MTX in human immunodeficiency virus (HIV)-related non-Hodgkin's
      lymphoma (NHL). Twenty-nine patients (22 men and 7 women), either newly diagnosed
      or pretreated, have been enrolled in the trial; the median age was 34 years, 45%
      had acquired immunodeficiency syndrome before lymphoma and 19 patients had less
      than 100 CD4 lymphocytes/microL. Histologic diagnoses were mainly Burkitt (27%)
      and diffuse large B-cell lymphoma (45%); extranodal involvement was present in 20
      patients. The treatment plan included three weekly courses of MTX at 1 g/m2 (days
      1, 8, and 15) plus oral AZT at 2 g/m2 (days 1, 2, and 3), 4 g/m2 (days 8, 9, and
      10), and 6 g/m2 (days 15, 16, and 17), plus leucovorin rescue. From the eleventh
      patient on, in case of complete or partial remission, the treatment was continued
      with three additional courses, using AZT at the maximum dose. In 26 evaluable
      patients, the total (complete + partial) response rate was 77% (95% confidence
      interval, 58% to 89%), with complete remission (CR) in 46% of the patients (95%
      confidence interval, 29% to 65%). The median CR duration was 12.8 months. Grade
      III-IV neutropenia and anemia were observed in 52% and 31% of the courses,
      respectively. There was one therapy-related death due to bacteremia followed by
      septic shock; the only other recorded infection was a herpes vaginalis. In
      conclusion, we suggest that AZT + MTX is an effective and well-tolerated regimen
      in HIV-related NHL.

PMID- 9002944
TI  - The development of human megakaryocytes: III. Development of mature
      megakaryocytes from highly purified committed progenitors in synthetic culture
      media and inhibition of thrombopoietin-induced polyploidization by interleukin-3.
AB  - Megakaryocyte (MK) progenitors, CD34+CD41+ cells, were isolated from human bone
      marrow with a purity greater than 98% and a viability of 95%, using affinity
      techniques with magnetic beads followed by fluorescence-activated cell sorting.
      These cells were incubated in synthetic media containing the cytokines
      thrombopoietin (TPO), interleukin-3 (IL-3), stem cell factor (SCF), and IL-6,
      obviating the confounding effects of serum growth factors or cytokine secretions
      of non-MK cells on MK maturation. MK number, MK colony-forming units (CFU-MK),
      and MK ploidy and phenotype were examined during 7 days in culture. TPO in serum
      free cultures without any other exogenously added cytokine supported MK growth
      and maturation. SCF synergized with TPO to augment MK production and maturation
      and could partially replace it under some conditions. Both TPO and IL-3 alone
      increased MK number (12- and 5-fold, respectively) and CFU-MK (approximately 15
      fold each). SCF alone had no effect on MK proliferation in the absence of TPO,
      but increased both MK number and CFU-MK by 1.5- to 2.0-fold in the presence of
      TPO. When combined with IL-3, SCF increased both MK number and CFU-MK by 15- to
      20-fold in the absence of TPO. In the presence of TPO, the combination of IL-3
      and SCF produced only modest increases (1.5- to 2.0-fold) in both MK number and
      CFU-MK. The proportion of polyploid MK increased greater than fivefold in the
      presence of TPO. SCF had little effect on MK ploidy in the presence of TPO, but
      enhanced ploidy twofold to threefold in the absence of TPO. IL-3 alone never
      increased the level of polyploidization. Rather, it consistently inhibited TPO-
      and SCF-induced polyploidization of MK. This inhibition was observed in cultures
      with or without SCF or IL-6. Although IL-3 also supported the proliferation of
      CD41+ cells and CFU-MK production, the cells that developed under the influence
      of IL-3 were phenotypically unusual (CD41dim, CD42dim) and of relatively low
      ploidy. Mature MK were not produced. When added with TPO, IL-3 suppressed
      polyploidization. Therefore, TPO stimulates MK growth and maturation, whereas IL
      3 stimulates growth without maturation and may serve to conserve the immature MK
      compartment.

PMID- 9002945
TI  - Ectopic expression of the erythropoietin receptor in a murine interleukin-6
      dependent plasmacytoma cell line (TEPC-2027) confers proliferative responsiveness
      to erythropoietin.
AB  - To compare the signal transduction pathways used by erythropoietin (Epo) and
      interleukin-6 (IL-6), the cDNA for the murine Epo receptor (Epo-R) was introduced
      into an IL-6-responsive plasmacytoma cell line (TEPC-2027) by retrovirally
      mediated gene transfer. G418-resistant clones were amplified in IL-6 and studied
      for their ability to grow and differentiate in response to Epo. Epo-R synthesized
      from the viral gene showed the same affinity for Epo as did the receptor on
      erythroid cells; however, the numbers of Epo receptors expressed on the cell
      membrane varied among clones. After a delay of 3 to 5 days in the presence of
      Epo, all the clones studied proliferated as well in response to Epo as in
      response to IL-6. In response to IL-6, Stat3 was activated and JunB mRNA was
      accumulated, whereas in response to Epo, Jak2 and Stat5 were activated and JunB
      mRNA was not accumulated in Epo-R-expressing TEPC (Epo-R/TEPC) cells. These
      results suggest that Epo and IL-6 transduced their proliferative signals through
      different pathways. Further studies showed that, in Epo-R/TEPC cells, Epo neither
      induces the synthesis of erythroid-specific mRNA nor modifies the synthesis of
      gamma 1 lg heavy chain, suggesting that ectopic expression of the Epo-R in
      plasmacytoma cells does not modify their differentiative potential. The data show
      that Epo induces a proliferative response without differentiation providing a new
      cellular model for evaluating molecular events specific for proliferation.

PMID- 9002946
TI  - FLT3 ligand preserves the ability of human CD34+ progenitors to sustain long-term
      hematopoiesis in immune-deficient mice after ex vivo retroviral-mediated
      transduction.
AB  - Stromal support is required during retroviral-mediated transduction of human bone
      marrow-derived CD34+ cells to maintain the clonogenicity of the primitive
      progenitors. We hypothesized that the cytokine FLT3 ligand (FL) might be able to
      replace the maintenance role provided by the stroma. CD34+ progenitors from human
      bone marrow were transduced by the retroviral vector LN with the cytokines
      interleukin-3 (IL-3), IL-6, and stem cell factor (SCF) present in all cultures.
      Transductions were performed with or without stromal support and with or without
      the inclusion of 100 U/mL FL. No significant increase in gene transfer into
      colony-forming cells was obtained by the addition of FL to the cultures.
      Transduction and survival of more primitive human hematopoietic cells was
      determined by growth in immune-deficient mice for 7 to 8 months. Human myeloid
      cells, T lymphocytes, and colony-forming progenitors were recovered from the
      marrow of mice that had received human cells transduced on stroma or in
      suspension culture with IL-3, IL-6, SCF, and FL, but not with IL-3, IL-6, and SCF
      alone. LN provirus was detected by polymerase chain reaction in the marrow
      recovered from 9 of 10 mice transplanted with human CD34+ cells transduced with
      stromal support, 5 of 11 mice that received human cells transduced in suspension
      culture with FL, but none of the 10 mice that received human cells transduced in
      suspension culture without FL We conclude that FLT3 ligand, in conjunction with
      IL-3, IL-6, and SCF, preserves the generative capacity of primitive human
      hematopoietic cells during in vitro transductions in suspension culture.

PMID- 9002947
TI  - Upregulation of cortactin expression during the maturation of megakaryocytes.
AB  - Cortactin is a potent filamentous actin-binding protein acting as a prominent
      substrate of Src tyrosine kinases. We have evaluated cortactin expression in a
      series of murine tissues and shown an abundant expression of cortactin in
      megakaryocytes and platelets. Cortactin, but not its related protein HS1, is
      upregulated during the phorbol 12-myristate 13-acetate (PMA)-mediated maturation
      of a human megakaryoblastic cell line CMK. Although the expression of Src-related
      kinases is also upregulated more rapidly than cortactin in PMA-treated CMK cells,
      tyrosine phosphorylation of cortactin appears to be only transiently elevated 4
      days after PMA stimulation. In addition, cortactin expression is induced by
      thrombopoietin and interleukin-3 in megakaryocytes derived from murine bone
      marrow cells. Thus, cortactin represents a megakaryocyte-specific gene in bone
      marrow and the interaction of Src kinases with cortactin may be involved in the
      maturation of megakaryocytes.

PMID- 9002948
TI  - The unexpected G0/G1 cell cycle status of mobilized hematopoietic stem cells from
      peripheral blood.
AB  - Treatment with a combination of cytokines and chemotherapy can effectively
      stimulate the release of hematopoietic stem cells (HSC) into the peripheral blood
      (PB), which can then be harvested for transplantation. The cell cycle status of
      the harvested HSC from mobilized PB (MPB) is of interest because of the impact
      that cell cycling may have on optimizing the conditions for ex vivo expansion,
      retrovirus-mediated gene transfer, and the engraftment of transplanted tissues.
      Therefore, we characterized the cell cycling status of mobilized HSC from mice
      and humans. The murine HSC, which express the phenotype c-kit+ Thy-1.1lo Lin-/lo
      Sca-1+, were purified from PB, bone marrow (BM), and spleen after the mice were
      treated with the mobilizing regimen of granulocyte colony-stimulating factor (G
      CSF) or a combination of cyclophosphamide (CTX) and G-CSF. Human HSC (CD34+ Thy
      1+ Lin-) and progenitor cells (CD34+ Thy-1-Lin-) were isolated from the BM of
      untreated healthy volunteers and from MPB of healthy volunteers and patients
      treated with G-CSF or a combination of CTX and GM-CSF. Cell cycle status was
      determined by quantitating the amount of DNA in the purified cells after staining
      with the dye Hoechst 33342. Fluorescence-activated cell sorting analysis of the
      progenitor cells from the murine and human samples showed an unexpected finding,
      ie, virtually none of the cells from the MPB was cycling. The G0/G1 status of HSC
      from MPB was surprising, because a significant proportion of HSC from BM are
      actively proliferating and, after mobilization, the HSC in the spleen and BM were
      also actively cycling.

PMID- 9002949
TI  - Homodimerization of erythropoietin receptor by a bivalent monoclonal antibody
      triggers cell proliferation and differentiation of erythroid precursors.
AB  - Erythropoietin (EPO) stimulates proliferation and differentiation of erythroid
      progenitor cells. Several lines of evidence indicate that the most likely
      mechanism of EPO receptor (EPO-R) activation by EPO is homodimerization of the
      receptor on the surface of erythrocyte precursors. Therefore, we argued that it
      should be possible to raise EPO-R monoclonal antibodies (MoAbs) that would
      activate the receptor by dimerization and thus mimic EPO action. We have
      identified such an agonist MoAb (MoAb34) directed against the extracellular EPO
      binding domain of the EPO-R. This bivalent IgG antibody triggers the
      proliferation of EPO-dependent cell lines and induces differentiation of
      erythroid precursors in vitro. In contrast, the monovalent Fab fragment, which
      cannot dimerize the receptor, is completely inactive. The mechanism of receptor
      activation by homodimerization implies that at high ligand concentrations the
      formation of 1:1 receptor/ligand complexes is favored over 2:1 complexes, thereby
      turning the ligand agonist into an antagonist. Thus, EPO and MoAb34 should self
      antagonize at high concentrations in both cell proliferation and differentiation
      assays. Our data indeed demonstrate that EPO and MoAb34 antagonize ligand
      dependent cell proliferation with IC50 values of approximately 20 and 2 mumol/L,
      respectively. Erythroid colony formation (BFUe) is inhibited at MoAb34
      concentrations above 1 mumol/L. Furthermore, we analyzed the MoAb34:EPO-R
      interaction using a mathematic model describing antibody-mediated receptor
      dimerization. The data for proliferation and differentiation activity were
      consistent with the receptor dimer formation on the cell surface predicted by the
      model.

PMID- 9002950
TI  - Thrombopoietin signal transduction in purified murine megakaryocytes.
AB  - Thrombopoietin (TPO) is a recently cloned cytokine that binds to its receptor,
      Mpl, and promotes hematopoietic expansion and maturation, primarily of the
      megakaryocyte lineage. The signaling pathways responsible for these events are
      thought to involve the Janus family of nonreceptor tyrosine kinases (JAKs) and
      the signal transducers and activators of transcription (STATs), which are
      activated by tyrosine phosphorylation. Previous investigators have studied these
      molecules in engineered and naturally occurring cell lines. To investigate the
      molecular basis for TPO signal transduction in a more physiologic target, we
      determined the pattern of JAK and STAT activation in purified, normal urine
      megakaryocytes. These results are compared with those of established cell lines
      that only proliferate (Ba/F3- mMPL and DA-1-TPO) or only differentiate (L8057) in
      response to TPO. From these findings, a model is proposed to explain the
      physiologic roles of JAK2, TYK2, STAT3, and STAT5 in TPO signaling. Furthermore,
      previous studies of the physical interaction between Mpl and the JAKs are
      extended, showing a difference in the association of JAK2 and TYK2 with the TPO
      receptor. Finally, we show that, in the cell line Ba/F3-mMPL, the closely related
      proteins STAT5A and STAT5B are both activated by TPO stimulation and are capable
      of heterodimerization. Together, these results further our understanding of the
      early stages of megakaryocyte and platelet development.

PMID- 9002951
TI  - Mapping of the active site of recombinant human erythropoietin.
AB  - Recombinant human erythropoietin (rHuEPO) variants have been constructed to
      identify amino acid residues important for biological activity. Immunoassays were
      used to determine the effect of each mutation on rHuEPO folding. With this
      strategy, we could distinguish between mutations that affected bioactivity
      directly and those that affected bioactivity because the mutation altered rHuEPO
      conformation. Four regions were found to be important for bioactivity: amino
      acids 11 to 15, 44 to 51, 100 to 108, and 147 to 151. EPO variants could be
      divided into two groups according to the differential effects on EPO receptor
      binding activity and in vitro biologic activity. This suggests that rHuEPO has
      two separate receptor binding sites. Mutations in basic residues reduced the
      biologic activity, whereas mutations in acidic residues did not. This suggests
      that electrostatic interactions between rHuEPO and the human EPO receptor may
      involve positive charges on rHuEPO.

PMID- 9002952
TI  - Induction of hypoxia-inducible factor-1, erythropoietin, vascular endothelial
      growth factor, and glucose transporter-1 by hypoxia: evidence against a
      regulatory role for Src kinase.
AB  - The induction by hypoxia of genes such as erythropoietin, vascular endothelial
      growth factor (VEGF), and glucose transporter-1 (Glut-1) is mediated in part by a
      transcriptional complex termed hypoxia-inducible factor-1 (HIF-1). Several lines
      of evidence have implicated protein phosphorylation in the mechanism of
      activation of HIF-1 by hypoxia. Recent reports have described the activation of
      the tyrosine kinase src by severe hypoxia, and a role in the induction of VEGF by
      severe hypoxia has been proposed. This led us to examine whether src and related
      kinases operated more widely in the hypoxic induction of HIF-1 and HIF-1
      dependent genes regulated by hypoxia. Measurements of src kinase activity in
      cells exposed to varying severities of hypoxia showed activation by severe
      hypoxia (0.1% oxygen or catalyst induced anoxia), but not 1% oxygen. This
      contrasted with the marked induction of HIF-1 by exposure to 1% oxygen.
      Manipulations of src activity were produced by transient and stable transfection
      of Hep3B cells. Despite substantial changes in src activity, no alteration was
      seen in the normoxic or hypoxic expression of erythropoietin, VEGF, or Glut-1, or
      in the regulation of HIF-1-dependent reporter genes inducible by hypoxia.
      Similarly, we found that the expression of these genes in src- or c-src kinase
      deficient cells did not differ from wild-type cells at either 1% oxygen or more
      severe hypoxia. These results indicate that src is not critical for the hypoxic
      induction of HIF-1, erythropoietin, VEGF, or Glut-1.

PMID- 9002953
TI  - Exocytotic competence and intergranular fusion in cord blood-derived eosinophils
      during differentiation.
AB  - We studied degranulation of single cord blood-derived mononuclear cells
      differentiating to eosinophils in cultures containing recombinant human
      interleukin-5 (rhIL-5) and rhIL-3 by whole-cell patch-clamp capacitance
      measurements. As in mature cells, degranulation can be stimulated by
      intracellular application of guanosine-5'-O-(3-thiotriphosphate) (GTP) gamma S
      after 10 days in culture, simultaneously with the first morphological appearance
      of granules. These results demonstrate that the fusion machineries for exocytotic
      fusion are present and functional as soon as the granules are formed, presumably
      at the myeloblast stage. In the third week, the total amount of granules
      exocytosed upon stimulation is similar to that in mature eosinophils from
      peripheral blood. The capacitance step size distributions in promyelocytes and
      myelocytes confirm that mature large specific granules are formed by homotypic
      fusion of unit granules with similar size. Homotypic fusion is facilitated during
      early stages of differentiation associated with granulogenesis. Between day 10
      and day 35 in culture the plasma membrane area of resting cells decreases from
      approximately 700 microns2 to approximately 400 microns2, approaching the value
      of mature cells from peripheral blood. The most prominent decrease occurs between
      day 25 and day 35 and is accompanied by the appearance of an exocytotic component
      due to small vesicles. This suggests that a class of small secretory vesicles is
      formed by endocytosis during a late phase in maturation.

PMID- 9002954
TI  - Interactions between c-kit and stem cell factor are not required for B-cell
      development in vivo.
AB  - The receptor-type tyrosine kinase, c-kit is expressed in hematopoietic stem cells
      (HSC), myeloid, and lymphoid precursors. In c-kit ligand-deficient mice, absolute
      numbers of HSC are mildly reduced suggesting that c-kit is not essential for HSC
      development. However, c-kit- HSC cannot form spleen colonies or reconstitute
      hematopoietic functions in lethally irradiated recipient mice. Based on in in
      vitro experiments, a critical role of c-kit in B-cell development was suggested.
      Here we have investigated the B-cell development of c-kit-null mutant (W/W) mice
      in vivo. Furthermore, day 13 fetal liver cells from wild type or W/W mice were
      transferred into immunodeficient RAG-2-/- mice. Surprisingly, transferred c-kit-
      cells gave rise to all stages of immature B cells in the bone marrow and
      subsequently to mature conventional B2, as well as B1, type B cells in the
      recipients to the same extent as transferred wild type cells. Hence, in contrast
      to important roles of c-kit in the expansion of HSC and the generation of
      erythroid and myeloid lineages and T-cell precursors, c-kit- HSC can colonize the
      recipient bone marrow and differentiate into B cells in the absence of c-kit.

PMID- 9002955
TI  - Tumor necrosis factor-alpha- and interleukin-6-triggered mast cell development
      from mouse spleen cells.
AB  - We previously showed that interleukin-3 (IL-3) alone is not sufficient, although
      it is essential for murine mucosal-type mast cell development and that
      prostaglandin E (PGE) and interferon-gamma (IFN-gamma) are critical for survival
      or differentiation of mast cell precursors. We also confirmed that IL-4 is a key
      inhibitor for mast cell precursors despite being a growth factor of mast cells.
      In the present work, mouse spleen cells were cultured with recombinant (r) IL-1
      beta, rIL-5, rIL-6, rIL-9, granulocyte-macrophage colony-stimulating factor (GM
      CSF), stem cell factor (SCF), tumor transforming growth factor-beta (TGF-beta),
      or tumor necrosis factor-alpha (TNF-alpha) in the presence of endogenous IL-3.
      After 12 days of culture, mast cell development was induced by rIL-6 and rTNF
      alpha, rIL-1 beta, rIL-5, rGM-CSF, rTGF-beta and even the mast cell growth
      factors, rIL-9 and rSCF, failed to induce mast cell development. However, unlike
      IL-9 and SCF, IL-6 and TNF-alpha did not promote the growth of mast cells already
      developed. Macrophage may be one of the responsive cells of IL-6 and TNF-alpha in
      the cultures, because removal of macrophages greatly reduced the mast cell
      development induced by the cytokines. The actions of TNF-alpha and IL-6 were
      inhibited by indomethacin, an inhibitor for prostaglandin synthesis, and by
      neutralizing anti-IFN-gamma and anti-IL-3 antibodies. rIL-4, when added at the
      start of the culture, also inhibited mast cell development induced by rIL-6 and
      rTNF-alpha. Nevertheless, neutralizing anti-IL-6 and anti-TNF-alpha antibodies
      did not suppress mast cell development induced by PGE and IFN-gamma. TNF-alpha
      and IL-6 enhanced IFN-gamma production, but suppressed IL-4 production in the
      cultures. Mast cell numbers induced were inversely and directly proportional to
      IL-4 and IFN-gamma levels, respectively. These results indicate that inflammatory
      mediators as triggers are important for mast cell development although they are
      not the mast cell growth factors.

PMID- 9002956
TI  - Antithrombotic efficacy in the guinea pig of a derivative of human protein C with
      enhanced activation by thrombin.
AB  - Conversion by alpha-thrombin of the zymogen human protein C (HPC) to activated
      protein C (aPC) is an important physiologic feedback control mechanism for the
      coagulation cascade. Although activation of HPC by thrombomodulin-bound thrombin
      is relatively rapid, activation by free thrombin occurs at a significantly slower
      rate. Previously, we generated a "hyper-activatable" derivative of HPC (FLIN-Q3)
      with an increased activation rate by free alpha-thrombin in vitro. In this study,
      the antithrombotic efficacy of FLIN-Q3 was compared with both native zymogen and
      aPC in an arteriovenous shunt model of thrombosis in the guinea pig. Recombinant
      proteins were infused 15 minutes before and throughout a 15-minute period while
      blood was circulated from carotid to jugular through tubing that enclosed a
      thread on which fibrin was deposited. Parallel dose-dependent antithrombotic
      responses were observed. Under these non-steady-state conditions, the calculated
      infusion doses associated with a 50% reduction of thrombus mass were 2.7, 24, and
      250 mg/kg/h for aPC, FLIN-Q3, and HPC, respectively. Thrombus weight correlated
      inversely with plasma concentration of aPC, measured amidolytically, from either
      direct infusion of aPC or that generated from the zymogens in the animal, and
      similarly correlated inversely with anticoagulant activity measured by whole
      blood aPTT. Neither zymogen form showed significant aPC activity before shunt
      circulation, suggesting a requirement for exposure to thrombin. After the
      infusion was discontinued for 15 minutes, a second period of thrombus formation
      in the shunt demonstrated the ability of zymogen forms of PC, unlike aPC, to
      provide "on-demand" anticoagulant responses to repeated thrombotic stimuli. Thus,
      a "hyper-activatable" PC molecule such as FLIN-Q3 may represent a superior form
      of anticoagulant therapy than either the native zymogen or aPC.

PMID- 9002957
TI  - Monocytes upregulate endothelial cell expression of tissue factor: a role for
      cell-cell contact and cross-talk.
AB  - Monocytes and endothelial cells interact at sites of vascular injury during
      inflammatory response, thrombosis, and development of atherosclerotic lesions.
      Such interactions result in modulation of several biological functions of the two
      cell types. Because both cells, on appropriate stimulation, synthesize tissue
      factor (TF), we examined the effect of human umbilical vein endothelial cell
      (HUVEC)/monocyte coculture on the expression of TF. We found that the
      coincubation resulted in TF generation, which was maximal at 4 hours, increased
      with increasing numbers of monocytes, and required mRNA and protein synthesis.
      Supernatant from HUVEC/monocyte coculture induced TF activity in HUVECs, but not
      in monocytes, indicating that HUVEC were the cells responsible for the activity,
      and that soluble mediators were involved. Interleukin-1 beta (IL-1 beta) and
      tumor necrosis factor-alpha (TNF-alpha), well-known inducers of TF in HUVECs,
      were found in the supernatant from the coculture, and specific antibodies
      directed against either cytokine inhibited TF generation. The need of IL-1 beta
      and TNF-alpha synthesis in order to elicit TF expression was also suggested by
      the delay observed in TF mRNA formation and TF activity generation when monocytes
      were incubated with HUVECs. IL-1 beta and TNF-alpha antigen levels in the
      coculture supernatant, and, consequently, HUVEC TF expression, were inhibited in
      the presence of anti-CD18 monoclonal antibody. These findings emphasize the role
      of cell-cell contact and cross-talk in the procoagulant activity, which could be
      responsible for the thromboembolic complications observed in those vascular
      disorders in which monocyte infiltration is a common feature.

PMID- 9002958
TI  - A cysteine protease inhibitor prevents activation-induced T-cell apoptosis and
      death of peripheral blood cells from human immunodeficiency virus-infected
      individuals by inhibiting upregulation of Fas ligand.
AB  - Activation of T-cell hybridomas, preactivated normal T cells, and peripheral
      blood lymphocytes (PBL) from human immunodeficiency virus (HIV)-infected
      individuals results in apoptosis. In the first two cases, apoptosis is caused by
      the upregulation of Fas ligand (FasL) and its subsequent interaction with Fas;
      the mechanism for the spontaneous and activation-induced death of lymph node
      cells and PBL from HIV+ blood is not known. A number of protease inhibitors have
      been shown to prevent T-cell apoptosis under all of these circumstances, but the
      mechanism of action has not been determined. Here we show that the cysteine
      protease inhibitor E64d prevent activation-induced T hybridoma cell death by
      inhibiting the upregulation of FasL. Quantitative polymerase chain reaction (PCR)
      demonstrated that mRNA for FasL is expressed at low levels in fresh PBL from HIV
      infected blood, but increases in cultured PBL from both uninfected and HIV
      infected donors. The ex vivo apoptosis of PBL from HIV+ donors was prevented by
      adding the soluble extracellular domain of Fas, demonstrating a requisite role
      for Fas/ FasL interactions in this form of cell death. Furthermore, while having
      no effect on the death of PBL from HIV-infected blood stimulated directly via
      Fas, E64d inhibited FasL upregulation. Thus, aberrant apoptosis of cultured PBL
      from HIV-infected individuals is mediated by FasL and Fas, and E64d blocks this
      apoptosis by inhibiting the upregulation of FasL. These results are consistent
      with the hypothesis that the abnormal expression of Fas and the inducible
      expression of FasL, contributes to the immunodeficiency of patients with acquired
      immune deficiency syndrome and suggest that modulation of FasL expression could
      be an effective target for therapeutic intervention.

PMID- 9002959
TI  - Differential susceptibility to HIV-GP120-sensitized apoptosis in CD4+ T-cell
      clones with different T-helper phenotypes: role of CD95/CD95L interactions.
AB  - The susceptibility of Th1 and Th2 cell clones to apoptosis following HIV
      gp120/CD4 cross-linking and TCR activation was investigated. We show that only
      Th1 clones are susceptible to HIV-gp120-sensitized apoptosis, although both types
      of clones express similar levels of CD4 and bind similar amounts of recombinant
      gp120. Both types of clones, however, undergo apoptosis induced by CD95 cross
      linking with agonistic monoclonal antibody (MoAb). Apoptosis induced by gp120 in
      the Th1 clones is inhibited by either an anti-CD95 neutralizing MoAb or an anti
      CD95L neutralizing MoAb as well as by a specific interleukin-1 beta converting
      enzyme (ICE) inhibitor. When triggered to apoptosis by gp120, Th1 but not Th2
      clones express both cell-associated and soluble CD95L. The CD95L produced by Th1
      clones induces cell death, inhibitable by anti-CD95 neutralizing MoAb, of CD95
      positive Jurkat cells. These data suggest that, like activation-induced
      apoptosis, HIV-gp120 sensitized apoptosis in Th1 clones occurs via CD95/CD95L
      interaction and that lack or insufficient production of CD95L is responsible, at
      least in part, for the resistance of Th2 clones to such apoptosis.

PMID- 9002960
TI  - Interleukin-12 (IL-12) production in whole blood cultures from human
      immunodeficiency virus-infected individuals studied in relation to IL-10 and
      prostaglandin E2 production.
AB  - The role of interleukin-12 (IL-12) in Th1 cell differentiation is well
      established. The heterodimer p70, composed of a p40 and a p35 chain, is the
      biologically active form. IL-12 production by human monocytes is enhanced by
      interferon-gamma (IFN-gamma) and inhibited by IL-10 and prostaglandin E2 (PGE2).
      Peripheral blood mononuclear cells from human immunodeficiency virus (HIV)
      infected individuals reportedly have impaired IL-12 p40 and p70 production on
      stimulation with Staphylococcus aureus Cowan I (SAC) in vitro. Both PGE2 and IL
      10 previously were proposed to be instrumental in this defect in IL-12
      production. Here, we studied IL-12 p40 and p70 production in relation to IL-10
      and PGE2 production in whole blood cultures from HIV-infected individuals. On
      stimulation with lipopolysaccharide, IL-12 production was normal. However, on
      stimulation with SAC, IL-12 p40 and p70 production was decreased in HIV-infected
      individuals and correlated significantly with decreased peripheral blood CD4+ T
      cell number and T-cell reactivity to CD3 monoclonal antibody in vitro. However,
      IL-10 and PGE2 production in cultures from HIV-infected individuals was normal
      and did not relate to IL-12 production. In conclusion, IL-12 production by cells
      from HIV-infected individuals is impaired under certain conditions in vitro and
      this decrease is independent of IL-10 or PGE2 production.

PMID- 9002961
TI  - The role of hyperuricemia in the increased cytokine production after
      lipopolysaccharide challenge in neutropenic mice.
AB  - Patients with severe granulocytopenia are more susceptible to severe infections
      and sepsis. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF),
      interleukin-1 alpha (IL-1 alpha), and IL-1 beta play an important role in the
      pathophysiology of sepsis. The profile of these proinflammatory cytokines after
      lipopolysaccharide (LPS) challenge in cyclophosphamide-induced neutropenic mice
      was assessed, and possible mechanisms responsible for the modified cytokine
      production were studied. After LPS, both circulating concentrations of TNF and IL
      1 alpha in neutropenic mice were 50% to 200% higher than those of controls,
      whereas IL-1 beta concentrations were not modified. The kinetics of cytokine
      production were similar in neutropenic and control animals. The susceptibility of
      neutropenic mice to an LPS challenge was increased. The observed overproduction
      of TNF and IL-1 alpha was not due to a direct effect of cyclophosphamide
      treatment. Because circulating concentrations of uric acid were increased in the
      neutropenic mice, the effect of hypouricemic treatment with allopurinol and
      sodium bicarbonate was investigated; such treatment in neutropenic mice
      challenged with LPS was followed by an improved survival and a reduced
      proinflammatory cytokine production towards the concentrations in control mice.
      Hyperuricemia induced by repeated administrations of uric acid in normal mice led
      to an increased TNF production after LPS. In conclusion, neutropenic mice respond
      with enhanced cytokine production and increased susceptibility to an LPS
      challenge, and hyperuricemia probably plays an important role in this phenomenon.

PMID- 9002962
TI  - Bone marrow and thymus expression of interferon-gamma results in severe B-cell
      lineage reduction, T-cell lineage alterations, and hematopoietic progenitor
      deficiencies.
AB  - Interferon-gamma (IFN-gamma) is an immunoregulatory lymphokine that is primarily
      produced by T cells and natural killer cells. It has effects on T-cell, B-cell,
      and macrophage differentiation and maturation. We have developed transgenic mice
      that express elevated levels of IFN-gamma mRNA and protein by inserting multiple
      copies of murine IFN-gamma genomic DNA containing an Ig lambda-chain enhancer in
      the first intron. The founder line carrying eight copies of this transgene has
      eightfold to 15-fold more IFN-gamma-producing cells in the bone marrow and spleen
      than do nontransgenic littermates. Transgenic mice show a pronounced reduction in
      B-lineage cells in the bone marrow, spleen, and lymph nodes. In addition, single
      positive (CD4+,CD8- and CD4-,CD8+) thymocyte numbers are increased twofold, yet
      the number of splenic T cells is reduced by 50%. There is also a twofold to
      threefold decrease in the frequency and total number of myeloid progenitors in
      the bone marrow. Granulomatous lesions and residual degenerating cartilaginous
      masses are also present in the bones of these mice. Overall, our data show that
      the abnormal expression of IFN-gamma in these transgenic mice results in multiple
      alterations in the immune system. These animals provide an important model to
      examine the role of IFN-gamma expression on lymphoid and myeloid differentiation
      and function.

PMID- 9002963
TI  - Frequent jumping translocations of chromosomal segments involving the ABL
      oncogene alone or in combination with CD3-MLL genes in secondary leukemias.
AB  - Seven secondary leukemia patients were treated for solid tumors or malignant
      lymphoma with anticancer drugs or radiation. We studied bone marrow samples from
      these patients by fluorescence in situ hybridization (FISH). Of the seven
      patients, three had increased signals for the ABL oncogene (9q34) on interphase
      nuclei and at metaphase. One of the three patients also had four signals for the
      CD3 (MLL) region (11q23). Whole painting probes revealed that these chromosomal
      regions were translocated onto structurally abnormal chromosomes, resulting in
      partial tri-, tetra- or penta-somy of these regions. We called this type of
      translocation "segmental jumping translocation (SJT)." SJT of the ABL oncogene
      was not detected in samples from 15 patients with de novo acute myelocytic
      leukemia (AML), 12 with myelodysplastic syndrome (MDS), or 20 with chronic
      myelocytic leukemia (CML) at the chronic phase. Furthermore, monosomy 7 was also
      found in the patients with the gene amplification. These results indicate that
      SJT of ABL and/or CD3 (MLL) genes is associated with the leukemogenesis of
      secondary leukemia. The SJT may be one mechanism of gene amplification.

PMID- 9002964
TI  - Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance
      in non-Hodgkin's lymphomas.
AB  - Although the cause(s) of clinical drug resistance in non-Hodgkin's lymphomas
      (NHL) is unknown, in vitro studies suggest that abnormalities of the p53 gene,
      bcl-2 overexpression, and low tumor proliferation rates may increase chemotherapy
      resistance. We analyzed tumor tissue from 75 patients with relapsed/refractory
      NHL (Working Formulation A through H) for p53 mutation/overexpression
      (abnormality), bcl-2 expression, and tumor proliferation and correlated them with
      multiple clinical characteristics, response to therapy, disease-free survival,
      and overall survival (OS). All tumor biopsy specimens were obtained within 6
      weeks of treatment with EPOCH (infusional etoposide, vincristine, and doxorubicin
      and bolus prednisone and cyclophosphamide) chemotherapy. Overall, 16 (21%) tumors
      had a p53 abnormality. Of 13 tumors with overexpression, mutations were confirmed
      by sequence analysis in 11, and, in 44 tumors without overexpression, 3 showed
      mutations. A multivariate analysis showed that tumors with a p53 abnormality were
      more likely to be drug resistant than tumors with normal p53 (56% v 17%; P2 =
      .008) and to have a shorter median progression-free survival (PFS; 2.1 v 8.2
      months; P2 = .008) and OS (11.7 v 21.5 months; P2 = .038), respectively. The
      presence of a p53 abnormality did not correlate with any clinical characteristic,
      bcl-2 expression, or tumor proliferation. A significant correlation was found
      between low tumor proliferation and drug resistance in a univariate (P2 < .006)
      but not multivariate analysis. Patients with tumor proliferation of less than 80%
      were significantly more likely to have no response to therapy (31% v 6%) or to
      fail to achieve a complete response (16% v 44%) and tended to have shorter PFS
      and OS than did patients with higher proliferation. No significant association
      was found between bcl-2 expression and drug resistance, PFS or OS, although
      patients with intermediate-grade histologies and high bcl-2 expression tended to
      be drug resistant as compared with low level expressors (P2 < .065). Of interest
      was the finding of a significant association between high bcl-2 and low tumor
      proliferation (P2 = .0045). In studies that have found an association between
      high bcl-2 expression and short PFS, bcl-2 may have been a surrogate for low
      tumor proliferation. Further studies are warranted to examine this question.
      These results suggest that p53 mutation and low tumor proliferation, but not bcl
      2, may be important causes of clinical drug resistance in NHL.

PMID- 9002965
TI  - Evidence for the participation of interleukin-2 (IL-2) and IL-4 in the regulation
      of autonomous growth and tumorigenesis of transformed cells of lymphoid origin.
AB  - In the current study, we investigated the role of interleukin-2 (IL-2) and IL-4
      as autocrine growth factors responsible for autonomous growth of four murine
      tumor cell lines: LSA, a radiation leukemia virus-induced T-cell lymphoma; EL-4,
      a chemically triggered T-cell lymphoma; PE-3T, a T-cell line that underwent
      spontaneous transformation ex vivo; and P815, a mastocytoma. All tumor cell lines
      screened constitutively expressed IL-2 receptor (IL-2R) and IL-4R genes. However,
      only LSA and PE-3T cells expressed IL-2 and IL-4 genes constitutively, whereas EL
      4 and P815 tumor cells expressed only IL-4 but not IL-2. Monoclonal antibodies
      (MoAbs) against IL-2, IL-4, or a combination of these, as well as MoAbs against
      IL-2R significantly inhibited the proliferation of LSA but not that of other
      tumor cell lines ex vivo. To exclude the possibility that, in other tumor cell
      lines, the autocrine growth factor may interact with its receptor within the
      cell, the ability of antisense phosphorothioate oligonucleotides to inhibit the
      growth of the tumor cells was tested. The antisense phosphorothioate
      oligonucleotides specific for IL-2, IL-4, IL-2R beta, or IL-2R gamma chains,
      added in culture, could markedly inhibit the growth of LSA but not that of the
      other tumor cell lines screened. Inasmuch as IL-2R beta and IL-2R gamma subunits
      also serve as a component of the receptors for IL-4, IL-7, IL-9, and IL-15, the
      above data suggested that such cytokine redundancy was not responsible for
      autonomous growth of the other tumor cell lines. Addition of exogenous IL-2 or IL
      4 to the tumor cell cultures caused significant enhancement in the proliferation
      of PE-3T cells, whereas other cell lines were either not significantly affected
      or slightly inhibited from growing. Interestingly, the LSA tumor growth in nude
      mice was significantly inhibited after treatment of these mice with a combination
      of MoAbs against IL-2 and IL-4. Together, our studies show for the first time
      that IL-2 and IL-4 may serve as autocrine growth factors in the autonomous
      proliferation of tumor cells, particularly those that are retrovirally induced.
      Second, some tumor cell lines, despite expressing certain cytokines and their
      receptors constitutively, may not depend exclusively on such factors for
      autocrine growth.

PMID- 9002967
TI  - Mcl-1, a Bcl-2 family member, delays the death of hematopoietic cells under a
      variety of apoptosis-inducing conditions.
AB  - Mcl-1 is a member of the Bcl-2 family that was identified based on increased
      expression in myeloblastic leukemia cells undergoing differentiation. Mcl-1 was
      previously found to be similar to Bcl-2 in causing a delay in apoptotic cell
      death in Chinese hamster ovary cells. The work described here was aimed at
      determining whether Mcl-1 could also exert such an effect in hematopoietic cells,
      because endogenous Mcl-1 expression is prominent in the hematopoietic system. A
      further aim was to assess the effects of Mcl-1 in cells exposed to a variety of
      cytotoxic stimuli, because Bcl-2 is known to have a broad spectrum of activity.
      To approach these aims, FDC-P1 murine myeloid progenitor cells were transfected
      with vectors driving either constitutive or inducible expression of Mcl-1. The
      introduced Mcl-1 gene was found to cause a prolongation of viability under
      various conditions that cause apoptotic cell death, including exposure to
      cytotoxic agents (the chemotherapeutic drug etoposide, calcium ionophore, or UV
      irradiation) and the withdrawal of required growth factors. In addition, Mcl-1
      was found to interact with Bax, a member of the Bcl-2 family that promotes cell
      death as a homodimer but that can heterodimerize with Bcl-2 to promote cell
      viability. Although Mcl-1 prolonged cell viability, it did not prevent eventual
      cell death upon continuous exposure to a cytotoxic agent. Prolongation of
      viability was maximal when expression of Mcl-1 was induced before the application
      of the apoptotic stimulus, although some increase occurred if Mcl-1 was induced
      shortly thereafter and before overt apoptosis. Taken as a whole, these findings
      provide further parallels between Mcl-1 and Bcl-2, showing that Mcl-1 can
      interact with Bax in hematopoietic FDC-P1 cells and can prolong cell viability
      under a variety of cytotoxic conditions.

PMID- 9002966
TI  - Minimally differentiated acute myeloid leukemia (AML-M0): comparison of 25 cases
      with other French-American-British subtypes.
AB  - We compared the immunophenotypic and karyotypic features of 25 cases of minimally
      differentiated acute myeloid leukemia (AML-M0) with those of 247 cases comprising
      all AML French-American-British (FAB) classification. Myeloperoxidase (MPO) was
      detectable with a specific monoclonal antibody in all cases of AML-M0, whereas
      CD13 and CD33 were both negative in 4 of the 25 cases. Thus, anti-MPO reliably
      detects minimal myeloid differentiation in AML-M0. CD34 and terminal
      deoxynucleotidyl transferase (TdT) were more frequently expressed in AML-M0 (96%
      and 68% of the cases, respectively) than in the other FAB subsets (P < .001 for
      both). By contrast, GP-170 and CD7 were less frequently expressed in AML-M0 than
      in FAB classes such as M1, M4, and M5 (P = .02 and .003, respectively). A total
      of 80% of AML-M0 cases carried lymphoid markers (including TdT), and 48% showed a
      coordinate positivity for two or more of them. CD2, CD5, CD10, and CD19 were
      expressed in a similar fashion among the different FAB groups, whereas CD4
      expression was significantly more frequent in AML-M0, AML-M4, and AML-M5 (P =
      .014). AML-M0 was characterized by a more frequent occurrence of complex
      karyotypes. In addition, approximately 20% of cases had TdT positivity, complex
      karyotypes, and anomalies of chromosome 5 and/or 7, a pattern not observed in the
      other FAB subsets. Finally, 80% of anomalies of chromosome 5 and/or 7 in AML-M0
      were comprised within complex karyotypes, whereas only 13% of the remaining FAB
      cases carried this feature. In summary, AML-M0 frequently expresses
      immunophenotypic and karyotypic aspects that are likely to identify a "stem cell"
      pattern.

PMID- 9002968
TI  - Primary non-Hodgkin's lymphoma of the intestine: high prevalence of Epstein-Barr
      virus in Mexican lymphomas as compared with European cases.
AB  - Recent studies in Western European populations have shown that peripheral T-cell
      non-Hodgkin's lymphomas (T-NHLs) are associated with Epstein-Barr virus (EBV) in
      a higher percentage than sporadic B-cell NHL (B-NHLs), and that the frequency of
      EBV-positivity might be influenced by the primary site of the tumor. Because of
      the geographic differences in EBV expression in Burkitt's lymphoma (BL) and
      Hodgkin's disease (HD), and the lack of studies of sporadic NHL from developing
      countries, we decided to survey the presence of EBV in a series of primary
      intestinal lymphomas from patients in Mexico and in Western Europe, and to
      analyze whether EBV status is influenced by tumor phenotype, and geographic or
      ethnic determinants. Paraffin-embedded tissue from 43 primary intestinal NHLs (19
      cases from Mexico and 24 from Western Europe) were examined, including 17 high
      grade B-NHLs, 9 low grade B-NHLs, and 17 T-NHLs; 6 of which were enteropathy
      associated T-cell lymphomas. The distribution of histologic subtypes was similar
      in both groups. The presence of EBV was investigated with a combined approach
      using a nested polymerase chain reaction technique as well as
      immunohistochemistry for latent membrane protein-1 and in situ hybridization for
      EBV early RNA transcripts (EBER 1/2) RNAs. The median age of the Mexican patients
      was significantly lower than the median age of the European patients (32 v 62
      years). This difference was most pronounced in patients with T-cell lymphoma (24
      v 63 years). EBER-positive tumor cells were detected in 13 of the 43 (30%) cases
      of primary intestinal lymphoma, including 5 of 26 sporadic B-NHL (3 high grade
      and 2 low grade), and 8 of 17 T-NHL, all of which were classified as pleomorphic,
      medium and large cell. The rates of EBV-positivity were markedly different for
      European and Mexican cases. Whereas 7 of 7 (100%) T-NHL and 5 of 12 (42%)
      sporadic B-NHL of Mexican origin were EBER-positive, only 1 of 10 T-NHL and 0 of
      14 sporadic B-NHL from Europe showed EBER expression in tumor cells. Latent
      membrane protein was positive in only 2 of 43 cases, 1 of which was an EBER
      negative high grade B-NHL from Mexico that showed intact total mRNA in control
      hybridization. CD30 expression was found in 4 of 8 EBV-positive T-NHL and in none
      of the EBV-positive B-NHL. In contrast to European cases, intestinal NHLs from
      Mexico show a very high frequency of EBV-positivity, which is not limited to T
      NHL, but includes a significant proportion of B-NHL. This study strongly suggests
      that similar to HD and probably BL, there are important epidemiologic differences
      in EBV association in intestinal T-cell NHL between European and Mexican
      populations. These differences might be the result of environmental factors, for
      example, earlier contact with childhood viruses on intestinal lymphomagenesis.

PMID- 9002969
TI  - The amino terminal lectin-like domain of thrombomodulin is required for
      constitutive endocytosis.
AB  - Thrombomodulin (TM) is a multidomain protein that serves as a cofactor in a major
      natural anticoagulant system. To further characterize the structure-function of
      TM, we have transfected COS cells with different truncated forms of TM. In the
      first form, COS cells expressing TM that lacks the putative signal peptide (17
      residues); the lectin-like, hydrophobic N-terminal domain (226 residues); and 12
      residues of the first epidermal growth factor (EGF)-like repeat (COSdel.238
      cells) were found to function normally with respect to TM transport to the cell
      surface and thrombin-dependent protein C activation. However, in contrast to wild
      type TM, as visually studied by immunofluorescence and immunogold electron
      microscopy, the COSdel.238 cells did not constitutively internalize anti-TM-TM or
      thrombin-TM complexes. To identify the region responsible for mediating the
      endocytic process, deletant forms of TM lacking either the lectin-like region
      (residues 2-155) or the hydrophobic region of the N-terminal domain (residues 161
      202) were expressed in COS cells (COSdel.2-155 and COSdel.161-202, respectively).
      Protein C cofactor activity was maintained in both cells. Although the COSdel.161
      202 cells behaved similarly to wild-type TM-transfected cells, visual studies
      showed a lack of constitutive internalization of thrombin-TM or anti-TM-TM
      complexes in the COSdel.2-155 cells. We conclude that the lectin-like domain of
      human TM serves to regulate cell surface expression of TM via the endocytic route
      and therefore may also play a major physiologic role in controlling intracellular
      and extracellular accumulation of thrombin in a variety of biologic systems.

PMID- 9002970
TI  - Formation of multinucleated giant cells in vitro is dependent on the stage of
      monocyte to macrophage maturation.
AB  - Multinucleated giant cells (MGC) are a common feature of granulomas that develop
      during various inflammatory reactions. MGC originate from fusion of monocytes or
      macrophages, but the exact mechanism of their generation is still unclear. In the
      present study, we investigated the influence of monocyte to macrophage maturation
      on the ability of human monocytes/macrophages to fuse with each other. MGC were
      generated in vitro by stimulation of human peripheral blood monocytes with
      cytokine containing supernatants. With freshly isolated monocytes, fusion rates
      of up to 90% were obtained. When monocyte to macrophage maturation was induced by
      culturing the cells in human serum, fusion rates gradually decreased with
      advancing time of the preceding culture (corresponding to the stage of
      differentiation) and almost no MGC formation could be obtained with 8-day-old
      macrophages. In contrast, fusion rates did not decrease when monocytes had been
      cultured under serum free conditions before stimulation. When freshly isolated
      monocytes were added to 1-week cultured macrophages, which had been membrane
      labeled with a fluorochrome, fusion between the two populations could be induced.
      Because the ability for intracellular killing of certain pathogens is reduced in
      macrophages, fusion with monocytes (newly arriving at the site of inflammation)
      may represent an attempt to restore this capacity.

PMID- 9002971
TI  - p15s (15-kD antimicrobial proteins) are stored in the secondary granules of
      Rabbit granulocytes: implications for antibacterial synergy with the
      bactericidal/permeability-increasing protein in inflammatory fluids.
AB  - The bactericidal potency toward complement-resistant Escherichia coli of
      bactericidal/permeability-increasing protein (BPI) released from
      polymorphonuclear leukocytes (PMNs) in glycogen-induced inflammatory peritoneal
      exudates of rabbits is dependent on synergy with extracellular p15s. This synergy
      depends on the high molar ratio of p15s to BPI in the extracellular fluid
      (approximately 50:1), which greatly exceeds the intracellular ratio
      (approximately 5:1). To explore the possible basis of the greater accumulation of
      p15s in inflammatory fluid, we examined the subcellular localization of BPI and
      p15 in PMNs. Immunogold electron microscopy confirmed the storage of BPI in
      primary granules and showed that p15s are stored in secondary granules. Reverse
      transcription polymerase chain reaction of density-fractionated rabbit bone
      marrow cells verified that p15s are expressed later than BPI during myeloid
      differentiation. As the inflammatory response evolves, p15 mRNA appears earlier
      in blood and exudate cells than mRNA for BPI, consistent with release of
      progressively less mature precursors from bone marrow. Finally, Ca(2+)-ionophore
      mediated exocytosis of p15s occurs more readily than release of BPI. We therefore
      propose that localization of a synergistic partner of BPI (p15s) in more readily
      released secondary granules allows the neutrophil to mobilize potent BPI
      dependent antibacterial activity extracellularly without significant depletion of
      intracellular BPI stores.

PMID- 9002972
TI  - Regulation of cellular iron metabolism by erythropoietin: activation of iron
      regulatory protein and upregulation of transferrin receptor expression in
      erythroid cells.
AB  - Erythropoietin (Epo) is the central regulator of red blood cell production and
      acts primarily by inducing proliferation and differentiation of erythroid
      progenitor cells. Because a sufficient supply of iron is a prerequisite for
      erythroid proliferation and hemoglobin synthesis, we have investigated whether
      Epo can regulate cellular iron metabolism. We present here a novel biologic
      function of Epo, namely as a potential modulator of cellular iron homeostasis. We
      show that, in human (K562) and murine erythroleukemic cells (MEL), Epo enhances
      the binding affinity of iron-regulatory protein (IRP)-1, the central regulator of
      cellular iron metabolism, to specific RNA stem-loop structures, known as iron
      responsive elements (IREs). Activation of IRP-1 by Epo is associated with a
      marked increase in transferrin receptor (trf-rec) mRNA levels in K562 and MEL,
      enhanced cell surface expression of trf-recs, and increased uptake of iron into
      cells. These findings are in agreement with the well-established mechanism
      whereby high-affinity binding of IRPs to IREs stabilizes trf-rec mRNA by
      protecting it from degradation by a specific RNase. The effects of Epo on IRE
      binding of IRPs were not observed in human myelomonocytic cells (THP-1), which
      indicates that this response to Epo is not a general mechanism observed in all
      cells but is likely to be erythroid-specific. Our results provide evidence for a
      direct functional connection between Epo biology and iron metabolism by which Epo
      increases iron uptake into erythroid progenitor cells via posttranscriptional
      induction of trf-rec expression. Our data suggest that sequential administration
      of Epo and iron might improve the response to Epo therapy in some anemias.

PMID- 9002973
TI  - Characterization of adult alpha- and beta-globin genes in the zebrafish.
AB  - Developmental switching of hemoglobins (Hbs) occurs in most vertebrates, yet the
      cellular and molecular basis for this process remains elusive. The zebrafish is a
      new genetic and developmental system that can be used to study embryogenesis, and
      mutants with a variety of defects in hematopoiesis have recently been derived. To
      initiate our studies on Hb switching in this organism, we have characterized the
      globins expressed in the adult. Reversed-phase high performance liquid
      chromatography and mass spectrometric analyses of adult peripheral blood
      hemolysates showed that there are three major alpha globins and two beta globins
      in circulating erythroid cells. In addition, we have isolated and characterized
      zebrafish adult alpha- and beta-globin cDNA clones that encode some of these
      globins. High levels of alpha- and beta-globin gene expression were detected in
      adult erythroid cells, whereas embryonic erythroid cells expressed little, if
      any, of these RNAs. We have also shown that the alpha- and beta-globin genes are
      tightly linked on the same chromosome and are arrayed in a 3'-5' to 5'-3'
      configuration, respectively. The characterization of these genes and regulatory
      elements in this globin locus will provide insight into the process of globin
      gene transcription. With these reagents, future studies of Hb switching in
      zebrafish mutants with defective hematopoiesis will be possible.

PMID- 9002974
TI  - Detection of Duffy antigen in the plasma membranes and caveolae of vascular
      endothelial and epithelial cells of nonerythroid organs.
AB  - The nonerythroid expression of the Duffy blood group protein (gp-Fy) was confined
      to certain cell types. Immunocytochemistry studies of the kidney showed gp-Fy in
      the endothelium of glomeruli, peritubular capillaries, vasa recta, and the
      principal cells (epithelial) of collecting ducts. Gp-Fy was also produced in the
      endothelial cells of large venules and epithelial cells (type-I) of pulmonary
      alveoli. In the thyroid, only the endothelial cells of capillaries produced gp
      Fy. In the spleen, the endothelial cells of capillaries, high endothelial venule,
      and sinusoids produced abundant gp-Fy. Ultrastructural studies showed that apical
      and basolateral plasma membrane domains, including caveolae, had gp-Fy.
      Immunoblot analysis showed substantially less gp-Fy in nonerythroid cells than in
      erythrocytes. Moreover, the analyzed nonerythroid organs of Duffy-negative
      individuals did not produce more gp-Fy to compensate for the lack of this protein
      in their erythrocytes. The nucleotide sequence and the size of kidney mRNA from a
      Duffy-positive individual were the same as that of bone marrow. It is assumed,
      therefore, that nonerythroid Duffy protein is the product of the same gene as
      that of bone marrow. This notion is reinforced by the fact that nonerythroid and
      erythroid gp-Fy have the same antigenic domains.

PMID- 9002975
TI  - Globin gene switching in transgenic mice carrying HS2-globin gene constructs.
AB  - We have examined the pattern of human globin gene switching in transgenic mice
      containing three different gamma and beta gene constructs (HS2G gamma A gamma
      delta beta, HS2A gamma beta neo, and HS2A gamma en beta) and compared the results
      with previously described transgenics (HS2A gamma beta, HS2G gamma A gamma-117
      delta beta, and LCR epsilon G gamma A gamma delta beta). Developmental regulation
      was observed in all cases with identical patterns in lines bearing the same
      construct. Three different patterns of switching were observed: LCR epsilon G
      gamma A gamma delta beta and HS2A gamma beta neo mice switched rapidly, HS2G
      gamma A gamma delta beta and HS2G gamma A gamma-117 delta beta at an intermediate
      rate, and HS2A gamma beta and HS2A gamma en beta mice showed delayed switching,
      with a plateau in late fetal-early neonatal life and readily detectable levels of
      gamma mRNA in adults. No difference was observed in the time of switching of the
      HS2G gamma A gamma delta beta mice compared with those with the A gamma-117
      hereditary persistence of fetal hemoglobin mutation, but adult levels of gamma
      mRNA were significantly higher (approximately 5%) in lines carrying the mutation
      than in those without (approximately 1%). Reversion to the rapid switch of the
      LCR epsilon G gamma A gamma delta beta mice was observed in three lines with the
      HS2A gamma beta neo construct in which expression of the tk-neo gene was
      approximately equal to that of the globin genes. The inclusion of the A gamma
      enhancer in HS2A gamma beta mice did not alter the pattern of switching, or
      reduce the relatively high levels of gamma mRNA in these lines. However, unlike
      other HS2 mice, the combination of HS2 and the A gamma enhancer resulted in copy
      number-dependent expression in HS2A gamma en beta lines, with intrauterine death
      at approximately 12.5 days gestation at high copy numbers. These results
      demonstrate that numerous elements throughout the beta globin gene cluster
      interact to produce the correct pattern of developmental regulation of these
      genes. Furthermore, extinction of gamma gene expression in adult life is not
      completely autonomous and is incomplete when HS2 is the only LCR element present.

PMID- 9002977
TI  - Milder clinical course of sickle cell disease in patients with alpha thalassemia
      in the Indian subcontinent.

PMID- 9002976
TI  - Molecular monitoring of minimal residual disease in follicular and mantle cell
      non-Hodgkin's lymphomas treated with high-dose chemotherapy and peripheral blood
      progenitor cell autografting.
AB  - Minimal residual disease (MRD) was evaluated in 30 patients with follicular or
      mantle cell non-Hodgkin's lymphoma (NHL) undergoing an intensive treatment with
      high-dose sequential (HDS) chemotherapy and peripheral blood progenitor cell
      (PBPC) autografting. To minimize the potential tumor cell contamination, PBPC
      harvests were scheduled at the end of HDS pretransplant phase. All patients had
      advanced-stage disease and most of them presented with bone marrow (BM)
      involvement. A tumor marker could be generated in 90% of patients using bcl-2 or
      lg heavy-chain genes. MRD was analyzed on PBPC, BM harvests, and after
      autografting by polymerase chain reaction (PCR). All evaluable follicular and 6
      of 9 mantle cell patients achieved clinical complete remission. PCR negativity of
      PBPC and/or BM harvests was documented in 68% of follicular and 12% of mantle
      cell lymphomas. Molecular remission of PBPC and/or BM harvests was achieved in 9
      of 15 patients with overt marrow involvement and in all patients with only
      molecular marrow infiltration at onset. Molecular follow-up was conducted on 14
      patients: all 7 evaluable patients who received at least one PCR-negative graft
      maintained the negative status at a median follow-up of 24 months and none of
      them relapsed so far. Thus, the results show that (1) a molecular marker to
      monitor MRD can be obtained in most follicular and mantle cell NHL patients, (2)
      the HDS regimen may provide PCR-negative PBPC and/or BM harvests even from
      patients with BM disease, and (3) autograft with at least one PCR-negative
      harvest is associated with a durable clinical and molecular remission.

PMID- 9002978
TI  - Developmental outcome of unrelated donor bone marrow transplantation in children
      with Hurler syndrome.

PMID- 9002979
TI  - Deletion of 13q14.3 and not 13q12 is the most common genetic abnormality detected
      in chronic lymphocytic leukemia cells.

PMID- 9002980
TI  - There's something fishy and perhaps even fowl about the mammalian calcitonin
      receptor and its ligand.

PMID- 9002981
TI  - Regulation by calcitonin and glucocorticoids of calcitonin receptor gene
      expression in mouse osteoclasts.
AB  - We previously studied regulation of the calcitonin (CT) receptor (CTR) by
      glucocorticoid (GC) and CT in cultures of mature mouse osteoclast-like cells
      (OCLs). The present studies were designed to examine the interaction of CT and GC
      in regulation of the CTR in osteoclasts and the molecular mechanisms involved.
      Treatment of OCLs with 10(-7) M dexamethasone (Dex) increased the CTR number in a
      time-dependent manner, whereas treatment with 10(-9) M salmon CT (sCT) reduced
      CTR number; neither treatment changed receptor affinity. Dex pretreatment
      somewhat antagonized the CT-induced reduction in [125I]sCT specific binding. Dex
      increased, and sCT pretreatment decreased, the sCT-responsive adenylate cyclase
      activity in parallel with the change in receptor binding. Dex treatment resulted
      in an increase in CTR messenger RNA (mRNA) levels, as assessed by reverse
      transcription-PCR, indicating that the increased CTR number was mediated by de
      novo CTR synthesis. This effect was specific to GCs and was not reproduced by
      mineralocorticoids or sex steroids. Treatment with sCT resulted in a rapid and
      profound reduction in CTR mRNA expression, and this reductions was somewhat
      delayed by Dex pretreatment. OCLs were treated with 5,6-dichloro-1 beta-D
      ribofuranosyl benzimidazole to enable estimation of the mRNA decay rates in the
      absence of ongoing transcription. The stability of CTR mRNA was similar to the
      control value in Dex-treated OCLs, suggesting that the effect of Dex may be due
      to changes in transcriptional activity. Interestingly, transcriptional inhibition
      by 5,6-dichloro-1 beta-D-ribofuranosyl benzimidazole abolished the ability of CT
      to reduce CTR mRNA levels, suggesting that CT may act by increasing the rate of
      CTR mRNA decay, and that this effect requires ongoing transcription. The 3'
      untranslated region of the mouse CTR mRNA contains four copies of the AUUUA
      motif, as well as other A/U-rich sequences, which have been shown to determine
      the stability of other mRNA transcripts. The stability results were consistent
      with the results of the nuclear transcript run-on assay, which indicated that
      treatment with Dex enhanced the rate of transcription, whereas CT had no effect.
      These results show that GC and CT influence CTR expression by distinct mechanisms
      and provide the basis for identification of the cellular factors involved.

PMID- 9002982
TI  - Electrophoretic mobility and glycosylation characteristics of heterogeneously
      expressed calcitonin receptors.
AB  - The translated calcitonin receptor (CTR) complementary DNA sequences contain
      potential N-linked glycosylation sites within the extracellular N-terminus. We
      investigated the relative molecular mass (M(r)) and degree of N-linked
      glycosylation of five cloned CTRs (pig, rat C1a, rat C1b, human I1-ve, and human
      I1+ve), together with the pig hypothalamic CTR, to analyze the potential
      contribution of carbohydrate moieties to the molecular identity of these
      receptors. Receptors were cross-linked to 125I-salmon CT with the
      homobifunctional reagent bis(sulfosuccinimidyl) suberate. Autoradiographic
      analysis of the cross-linked receptors, following SDS-PAGE, revealed apparent
      M(r)S, ranging between 70,000 and 80,000 for the rat, human, and pig hypothalamic
      receptors. However, the cloned, expressed pig CTR was much smaller (approximately
      58,000). The lower M(r) of the cloned pig CTR appeared to be due to absence of N
      terminal residues, but this did not impact on ligand-receptor specificity when
      compared with the hypothalamic pig CTR. Cleavage under nondenaturing conditions
      of N-linked sugars from the CTRs using endoglycosidase F (Endo F), increased the
      electrophoretic mobility of all receptors, except the pig CTRs, by approximately
      10 kDa. Under denaturing conditions, electrophoretic mobilities increased by
      approximately 30 kDa for the rat C1a, rat C1b, and humanI1-ve (expressed in human
      embryonic kidney-293 cells) CTRs and by approximately 20 kDa for the cloned pig,
      pig hypothalamic, and human CTR isoforms (expressed in baby hamster kidney
      cells). Competition binding studies using glycosylated and partially
      deglycosylated (nondenaturing conditions) receptor preparations demonstrated no
      significant differences in binding affinity or specificity. Thus the CTRs are N
      linked glycoproteins whose degree of glycosylation is both cell-type and species
      dependent.

PMID- 9002983
TI  - Immunohistochemical and molecular characterization of the rat 11 beta
      hydroxysteroid dehydrogenase type II enzyme.
AB  - Mineralocorticoid action is facilitated by 11 beta-hydroxysteroid dehydrogenase
      type II (11 beta HSD2), which metabolizes glucocorticoids and allows aldosterone
      to bind to the nonselective mineralocorticoid receptor. We have recently
      demonstrated the presence of the 11 beta HSD2 protein in a wide range of human
      epithelia, suggesting that it is the sole isoform endowing specificity in man. In
      the present study we have used an immunopurified polyclonal antibody (RAH23)
      raised against a C-terminal peptide derived from the cloned rat 11 beta HSD2
      protein to perform immunohistochemical and molecular analysis in rat tissues. In
      frozen sections of rat kidney, strong staining was seen with the RAH23 antibody
      in the distal tubule; weaker staining was observed in the thick ascending loop of
      Henle and the medullary and papillary collecting ducts. Punctate cortical
      staining was observed in the fetus at 20 days gestation and in 8-day-old rats,
      with a noticeable increase in the staining pattern at 16 days of age. The kidney
      did not attain the adult pattern of staining until 28 days of age. Epithelia of
      ileum and colon also stained with RAH23, as did excretory ducts of the
      submandibular gland. Intrahepatic and excretory bile ducts displayed strong
      immunoreactivity in the epithelial lining. Rat adrenal glands showed evidence of
      the 11 beta HSD2 antigen in the zona fasciculata and zona reticularis, but not in
      the zona glomerulosa or medulla. Western blot analysis with the RAH23 antibody
      revealed strong bands in the kidney, colon, adrenal gland, and submandibular
      gland at 40 kDa, colinear with the migration of the cloned 11 beta HSD2 enzyme. A
      band of medium intensity was also seen at this size in the pancreas, whereas a
      band of moderate intensity was seen in the bile duct, and weaker bands were
      noticed in the stomach, small intestine, and liver, with a diffuse band at 36-42
      kDa in the prostate. Strong bands were seen in the pancreas and prostate at 78
      kDa, with weaker signals in the colon, adrenal, stomach, and bile duct. A number
      of tissues also displayed multiple bands at about 30 kDa. Enzymatic assays on
      tissue homogenates showed extensive conversion of corticosterone to its 11
      dehydro product in an NAD-dependent manner in the submandibular gland, adrenal
      gland, and kidney, but not in the pancreas or prostate. This study confirms the
      ubiquitous presence of 11 beta HSD2 in sodium-transporting epithelia,
      demonstrates the high level of 11 beta HSD2 protein and enzyme activity in the
      rat adrenal, and suggests a possible role for the enzyme in the biliary system.
      Further studies are required to determine the relevance of the various molecular
      species to the activity, latency, and processing of the enzyme.

PMID- 9002984
TI  - Effects of beta-adrenoceptor subtype stimulation on obese gene messenger
      ribonucleic acid and on leptin secretion in mouse brown adipocytes differentiated
      in culture.
AB  - The ob gene product is known to control food intake and energy expenditure. To
      determine whether thermogenic agents directly control ob gene expression, the
      effects of beta-adrenoceptor agonists on the level of the ob gene messenger RNA
      (mRNA) and on leptin secretion have been studied in mouse brown adipocytes
      differentiated in culture. These cells highly expressed the beta 3-adrenoceptor,
      the uncoupling protein, and the ob gene mRNAs. The ob gene was expressed in mouse
      brown adipocytes earlier than in mouse white adipocytes under the same culture
      conditions and to a similar level. The beta 3-, beta L-, and beta 2-adrenoceptor
      agonists BRL 37344, dobutamine, and terbutaline inhibited ob gene expression in
      mouse brown adipocytes differentiated in culture with EC50 values of 0.3, 1.0,
      and 85 nM, respectively. Leptin secretion by the cells under basal conditions was
      78 +/- 10 pg/microgram DNA-4 h and was decreased by exposure to the beta
      adrenoceptor agonists. The ob gene mRNA half-life was 9.4 h and was decreased to
      2.4 h by 1 nM BRL 37344, indicating that the inhibitory effect of the beta 3
      agonist might be due to destabilization of ob gene mRNA. (Bu)2cAMP (10-100
      microM) and forskolin (20 microM) mimicked the effect of the beta-adrenoceptor
      agonists. FFA (150-800 microM) had only a small inhibitory effect on ob gene mRNA
      expression. The results suggest the existence in brown adipose tissue of a
      retroregulatory pathway by which leptin production in inhibited when the
      sympathetic nervous system is stimulated.

PMID- 9002985
TI  - Androgen modulation of the messenger ribonucleic acid of retinoic acid receptors
      in the prostate, seminal vesicles, and kidney in the rat.
AB  - Previously, we reported that the steady state level of messenger RNA (mRNA)
      transcripts of retinoic acid receptors (RAR) alpha and gamma in the testes of 20
      day-old rats can be modulated by exogenous testosterone. These results suggest
      that androgen regulation of Sertoli cell functions may involve biochemical events
      mediated by RAR genes. In this study, we examined the effects of castration and
      testosterone replacement on the steady state level of mRNA transcripts for RAR
      alpha and gamma in the prostate, seminal vesicles, and kidney of the rat.
      Northern blot analysis revealed that in intact adult rats, the relative steady
      state levels of the 3.4- and 2.7-kilobase (kb) mRNA transcripts for RAR alpha and
      the 3.4-kb transcript for RAR gamma in the prostate were at least 20-fold higher
      than those in the seminal vesicles and kidney. The relatively high abundance of
      RAR mRNA transcripts in the prostate suggests the physiological importance of RAR
      mediated processes in this organ. Castration resulted in an increase in the level
      of RAR mRNA transcripts in the prostate and seminal vesicles, reaching a maximum
      of 2- to 4-fold in the prostate and 15- to 23-fold in the seminal vesicles within
      6 days. On the other hand, the levels of mRNA transcripts of RAR alpha and -gamma
      in the kidney were reduced by 40-50% 1 day after castration. The effects of
      castration on RAR mRNA levels in all three organs were prevented by implantation
      of 3-cm testosterone capsules at the time of castration, a regimen that provides
      physiological levels of serum testosterone. In a subsequent experiment, adult
      male rats were given a single sc injection of 2 mg testosterone 3 days after
      castration. This treatment resulted in an acute suppression of the level of RAR
      mRNA transcripts in all three organs within 30 min. Thereafter, the levels of RAR
      alpha and -gamma mRNA transcripts in the prostate continued to decrease, whereas
      those in the seminal vesicles returned to the castrated levels within 6 h. On the
      other hand, RAR mRNA levels in the kidney rebounded by 1 h and remained at the
      level found in the untreated castrated rats. These results demonstrate that the
      steady state level of mRNA transcripts for RAR alpha and -gamma in the prostate,
      seminal vesicles, and kidney can be modulated by testosterone in organ-specific
      manners, thus suggesting that the RAR-mediated processes may be involved in the
      effects of androgen in these organs. Furthermore, the relatively low increment in
      prostatic RAR mRNA levels after castration compared to that in the seminal
      vesicles demonstrates a difference in androgen responses between these two
      organs. This difference could dictate the efficacy of the effects of androgen on
      cellular function and may contribute to the disparate vulnerabilities to androgen
      related uncontrolled cell proliferation and/or malignancy in the prostate and
      seminal vesicles.

PMID- 9002986
TI  - Evidence that endogenous relaxin promotes growth of the vagina and uterus during
      pregnancy in gilts.
AB  - Recently, it was demonstrated that endogenous relaxin promotes growth of the
      vagina during the second half of pregnancy in rats and that administration of
      porcine relaxin promotes growth of the uterus in nonpregnant or early pregnant
      gilts. This study examined the effects of circulating relaxin on growth of both
      the vagina and uterus during the last two thirds of the 114-day gestation period
      in gilts. Furthermore, this study employed an in vitro immunohistochemical
      localization technique to determine whether the vagina and uterus in pigs have
      specific relaxin-binding sites. Three groups of pregnant gilts were used: sham
      ovariectomized controls (group C; n = 8), ovariectomized progesterone-treated
      (group OP; n = 6), and ovariectomized progesterone- plus relaxin-treated (group
      OPR; n = 7). Gilts were either sham ovariectomized or ovariectomized on day 40 of
      gestation. Hormone replacement therapy with progesterone (group OP), progesterone
      plus relaxin (group OPR), or hormone vehicles (group C) began on day 38
      (progesterone) or day 40 (relaxin) and continued until day 110. On day 110, the
      vagina and uterus were collected, and wet weight, dry weight, and percent
      hydration were determined. Small pieces (2-3 cm3) of the vagina and uterus from
      groups C and OP were frozen and cryosectioned for the immunohistochemical
      localization of relaxin-binding sites. Relaxin promoted growth of both the vagina
      and uterus. The wet weights of both the vagina and uterus in relaxin-deficient
      gilts (group OP) were lower (P < 0.05) than those in controls (group C), and
      relaxin replacement therapy (group OPR) restored the wet weights of both tissues
      to values that did not differ from those in controls. The mean dry weights and
      percent hydrations in the vagina and uterus did not differ among treatments.
      Immunohistochemical localization studies in the vagina and uterus demonstrated
      that specific and saturable binding of relaxin was localized in the same cell
      types of both tissues, namely epithelial cells (luminal in vagina, and both
      luminal and glandular in uterus), smooth muscle cells (both circular and
      longitudinal in vagina, and myometrial in uterus), and cells associated with
      blood vessels. In conclusion, this study provides evidence that circulating
      relaxin promotes growth of both the vagina and uterus during pregnancy in the
      pig. Furthermore, this study provides evidence that both the vagina and uterus
      contain specific and saturable relaxin-binding sites in epithelial cells, smooth
      muscle cells, and cells associated with blood vessels. We conclude that these
      cells probably initiate relaxin's effects on the vagina and uterus of the
      pregnant pig.

PMID- 9002987
TI  - Comparative effect of pituitary adenylate cyclase-activating polypeptide on
      aldosterone secretion in normal bovine and human tumorous adrenal cells.
AB  - The purpose of this study was to investigate the mechanisms of action of
      pituitary adenylate cyclase-activating polypeptide (PACAP) in stimulating
      aldosterone production in two different models: bovine adrenal zona glomerulosa
      (ZG) cells in primary culture and the human adrenocortical carcinoma cell line
      H295R. PACAP binds to two major groups of receptors: type I, which prefers
      PACAP38 and PACAP27 over vasoactive intestinal peptide (VIP); and type II, which
      has approximately equal affinity for PACAP38, PACAP27, and VIP. The type I
      subclass comprises multiple splice variants that can be distinguished by their
      specificity to PACAP38 and PACAP27 in their activation of adenylate cyclase and
      phospholipase C. Type II PACAP/ VIP receptors couple only to AC. In bovine ZG
      cells, PACAP38 and PACAP27 stimulated aldosterone production in a dose-dependent
      manner, whereas VIP was ineffective. In H295R cells, PACAP38, PACAP27, and VIP
      dose-dependently stimulated aldosterone production with roughly the same ED50. In
      bovine ZG cells, PACAP38 and PACAP27 stimulated cAMP production with similar
      efficacy, whereas VIP had no effect. In H295R cells, all three peptides
      stimulated cAMP accumulation. PACAP38 and PACAP27 also activated PLC in bovine ZG
      cells as they induced an increase in Ins(1,4,5)Ps production. In H295R cells,
      neither of these peptides was able to stimulate IP turnover. These results
      indicate that PACAP stimulation of aldosterone production is mediated by the
      PVR1s or the PVR1hop splice variants of the type I PACAP-specific receptor
      subtype in bovine ZG cells, whereas only type II PACAP/VIP receptors seemed to
      occur in the human H295R cell line. In addition, PACAP-stimulated aldosterone
      production was inhibited by atrial natriuretic peptide in bovine and human
      adrenocortical cells, however not by the same mechanism. This further supports
      species-specific and/or cell type-specific signaling pathways for PACAP in the
      regulation of aldosterone production.

PMID- 9002988
TI  - Cryptic gonadotropin-releasing hormone receptors of rat pituitary cells in
      culture are unmasked by epidermal growth factor.
AB  - Protein kinase activators as well as several neuropeptides are able to increase
      the GnRH-binding capacity of cultured adenohypophyseal cells. To determine
      whether such up-regulation of GnRH-binding sites can be achieved by a
      substance(s) endogenous to the pituitary, binding experiments were performed
      after exposure of cells to increasing amounts of medium conditioned by incubation
      with primary cultures of adenohypophyseal cells for 4 days. Addition of the
      conditioned medium elicited a 50% increase in GnRH binding. Characterization of
      the agent(s) responsible for the effect was attempted by submitting the
      conditioned medium to molecular sieve filtration, adding or immunoprecipitating
      endogenous substances, and comparing the susceptibilities of the responses to
      various inhibitors of transduction processes. Fractionation of the medium
      indicated that active molecules were of a proteic nature, with M(r) ranging from
      5,000-10,000. Among major endogenous moieties corresponding to these criteria
      [epidermal] growth factor (EGF), transforming growth factor-alpha, and insulin
      like growth factors I and II), only the first two exhibited properties similar to
      those of the conditioned medium. EGF stimulated binding with an EC50 of 3.6 +/-
      0.8 pM. Immunoprecipitation of EGF, but not transforming growth factor-alpha,
      inactivated the conditioned medium. The effects of both conditioned medium and
      EGF were inhibited by herbimycin, a tyrosine kinase inhibitor; U73122, a
      phospholipase C inhibitor; and prior desensitization of protein kinase C. In
      contrast, both were insensitive to pertussis toxin pretreatment. In parallel, EGF
      did not increase LH secretion by itself, but potentiated its response to GnRH in
      a concentration range of 1 pM to 1 nM, resulting in a shift of the curve toward
      lower values of GnRH. It is concluded that EGF is able to control the
      accessibility of binding sites to GnRH and to potentiate the responsiveness of
      gonadotropes to the decapeptide.

PMID- 9002989
TI  - Effects of growth hormone secretagogues in the transgenic growth-retarded (Tgr)
      rat.
AB  - Exogenous GH inhibits endogenous GH release by hypothalamic feedback. We have
      recently exploited this to generate transgenic growth-retarded (Tgr) rats, in
      which human GH is expressed in the hypothalamus, under the control of the rat GRF
      gene promoter. These rats show reduced pituitary size, GH deficiency, and
      dominant dwarfism, but are large enough for serial blood sampling studies to
      examine their spontaneous GH secretion and responses to GRF, somatostatin, and GH
      releasing peptide-6 (GHRP-6). Like their normal wild-type littermates, Tgr rats
      show a sexually dimorphic pattern of GH secretion; males secrete GH in 3-h
      episodes, whereas females exhibit a more continuous irregular output, with higher
      baseline GH levels. In anesthetized male Tgr rats, the GH responses to GRF or
      GHRP-6 were markedly reduced compared with those of their nontransgenic
      littermates, but the differences were smaller in females. Despite the reduction
      in pituitary GH, peak plasma GH responses to serial GRF injections in conscious
      Tgr males or intermittent somatostatin infusions in conscious Tgr females were
      indistinguishable from the responses in their wild-type littermates. Furthermore,
      7-day iv infusions of GRF (12.5-100 micrograms/day), given either continuously or
      as a pulsatile infusion stimulated growth in Tgr rats, as did pulsatile infusions
      of GHRP-6. Thus, despite their pituitary GH deficiency and dwarfism, Tgr rats
      maintain a sexually dimorphic pattern of GH release and can produce large GH
      secretory responses to exogenous secretagogues. They represent the first genetic
      model of GH deficiency in the rat in which dwarfism can be corrected by treatment
      with exogenous GH secretagogues.

PMID- 9002990
TI  - Characterization of soluble, disulfide bond-stabilized, prokaryotically expressed
      human thyrotropin receptor ectodomain.
AB  - To study the interaction of TSH receptor (TSHR) autoantibodies with receptor
      protein; it is necessary first to express the receptor in the proper conformation
      including the formation of correct disulfide bridges. However, the reducing
      environment of the Escherichia coli (E. coli) cytoplasm prevents the generation
      of protein disulfide bonds and limits the solubility and immunoreactivity of
      recombinant human TSHR (hTSHR) products. To circumvent these limitations, hTSHR
      complementary DNA encoding the extracellular domain (hTSHR-ecd; amino acids 21
      415) was inserted into the vector pGEX-2TK by directional cloning and used to
      transform the thioredoxin reductase mutant strain of E. coli (Ad494), which
      allowed formation of disulfide bonds in the cytoplasm. After induction, the
      expressed soluble hTSHR-ecd fusion protein was detected by Western blot analysis
      using a monoclonal antibody directed against hTSHR amino acids 21-35. This showed
      that over 50% of the expressed hTSHR-ecd was soluble in contrast to expression in
      a wild-type E. coli (strain alpha F'), where the majority of the recombinant
      receptor was insoluble. The soluble recombinant receptor was affinity purified
      and characterized. Under nonreducing SDS-PAGE conditions, the soluble hTSHR-ecd
      migrated as refolded, disulfide bond-stabilized, multimeric species, whose
      formation was independent of fusion partner protein. This product was found to be
      biologically active as evidenced by the inhibition of the binding of 125I-TSH to
      the full-length hTSHR expressed in transfected CHO cells and was used to develop
      a competitive capture enzyme-linked immunosorbent assay for mapping of hTSHR
      antibody epitopes. Hence, hTSHR-ecd produced in bacteria with a thioredoxin
      reductase mutation was found to be highly soluble and biologically relevant.

PMID- 9002991
TI  - Effect of gonadotropin-releasing hormone (GnRH) pulse frequency on serum and
      pituitary concentrations of luteinizing hormone and follicle-stimulating hormone,
      GnRH receptors, and messenger ribonucleic acid for gonadotropin subunits in cows.
AB  - Thirty-two nutritionally anestrous cows were used to determine the effect of the
      frequency of exogenous GnRH pulses on ovarian follicular growth, serum
      concentrations of LH and FSH, and concentrations of LH, FSH, GnRH receptors (GnRH
      R), messenger RNA (mRNA) for GnRH-R, and mRNA for gonadotropin subunits in the
      pituitary. Cows were randomly assigned to one of four treatments: 2 micrograms
      GnRH infused (i.v.) continuously during 1 h, 2 micrograms GnRH infused during 5
      min once every hour, 2 micrograms GnRH infused during 5 min once every fourth
      hour, or saline (control) for 13 days. Infusion of GnRH every hour increased LH
      concentrations in serum (P < 0.05), but FSH concentrations were not affected by
      GnRH infusion. Luteal activity (LA) was assessed by the presence of corpora lutea
      and/or serum progesterone greater than 1 ng/ml. Six of eight cows infused with
      GnRH every hour had LA by day 13, whereas only 25% of cows infused either
      continuously or with a pulse every fourth hour had LA by day 13. None of the
      control cows had LA during the experiment (P < 0.01). Concentrations of LH and
      FSH in the pituitary were significantly reduced when GnRH was infused hourly or
      continuously. Concentrations of common alpha and FSH beta mRNA were not
      influenced by treatment. However, continuous infusion of GnRH decreased (P <
      0.05) LH beta mRNA subunit. Concentrations of GnRH-R (P < 0.1) and GnRH-R mRNA (P
      < 0.05) were reduced when GnRH was infused continuously. We concluded that
      pulsatile secretion of LH is necessary for follicular growth and LA in beef
      cattle, and GnRH treatment differentially regulates LH and FSH gene transcription
      and serum concentrations of LH and FSH in cattle.

PMID- 9002992
TI  - Thyroid-stimulating hormone-induced down-regulation of thyroid transcription
      factor 1 in rat thyroid FRTL-5 cells.
AB  - Thyroid transcription factor 1 (TTF-1) is thought to play an important role in
      the expression of genes that encode thyroid-specific proteins such as
      thyroglobulin, thyroid peroxidase, and TSH-receptor. The role of TSH in the
      regulation of TTF-1 messenger RNA (mRNA) and protein abundance was investigated
      in rat thyroid FRTL-5 cells. Northern blot analysis revealed that TSH reduced TTF
      1 mRNA abundance in a dose- and time-dependent manner. Immunoblot analysis with
      rabbit antibodies prepared against a recombinant fragment of TTF-1 expressed in
      bacteria showed that TSH also reduced the amount of TTF-1 protein in FRTL-5
      cells. Whereas the effect of TSH on TTF-1 mRNA was apparent after 3 h, the effect
      on TTF-1 protein was not apparent until 12 h after TSH addition to the cells.
      Both TTF-1 mRNA and protein were significantly decreased after the addition of
      (Bu)2 cAMP or forskolin for 24 h, whereas they were not decreased by 12-O
      tetradecanoyl-phorbol-13-acetate. These results indicate that TSH down-regulates
      TTF-1 expression in FRTL-5 cells via the cAMP pathway.

PMID- 9002993
TI  - Insulin promotes and cyclic adenosine 3',5'-monophosphate impairs functional
      insertion of insulin receptors in the plasma membrane of rat adipocytes: evidence
      for opposing effects of tyrosine and serine/threonine phosphorylation.
AB  - The aim of the present study was to elucidate events in the plasma membrane (PM)
      associated with the previously described effect of insulin to rapidly enhance the
      number of cell surface insulin binding sites in rat adipocytes. [125I]insulin was
      cross-linked to cell surface insulin receptors of intact cells that had been
      preincubated with or without insulin. Subsequently prepared PM displayed a
      approximately 3-fold increase in bound [125I]insulin when cells had been
      pretreated with 6 nM insulin for 20 min compared to membranes from control cells,
      and SDS-PAGE with autoradiography showed that this occurred at the insulin
      receptor alpha-subunit. The magnitude of the effect was similar to that found for
      insulin binding to intact cells that had been preincubated with insulin. In
      contrast, the insulin binding capacity in the PM was not affected by prior
      treatment of cells with insulin when assessed with the addition of [125I]insulin
      directly to solubilized PM; this suggests an unchanged total number of PM
      receptors. Thus, the enhancement of cell surface insulin binding capacity
      produced by insulin is not due to the translocation of receptors, but instead
      appears to be confined to receptors already present in the PM. The addition of
      phospholipase C (from Clostridium perfringens), which cleaves PM phospholipids,
      mimicked the effect of insulin to enhance cell surface binding in adipocytes, and
      this suggests a pool of cryptic PM receptors. Both the nonmetabolizable cAMP
      analog N6-monobutyryl cAMP (N6-mbcAMP) and the serine/threonine phosphatase
      inhibitor okadaic acid abolished the effect of concomitant insulin treatment to
      increase binding capacity. In contrast, the tyrosine phosphatase inhibitor
      vanadate increased insulin binding even in the presence of okadaic acid or N6
      mbcAMP. The effect of N6-mbcAMP to impair cell surface insulin binding was also
      evident in the presence of a peptide derived from the major histocompatibility
      complex type I that effectively impairs receptor internalization, but the amount
      of PM receptors assessed by immunoblot was unaltered. Taken together, the data
      suggest that insulin exposure leads to the uncovering of cryptic receptors
      associated with the PM. It is also suggested that tyrosine phosphorylation
      promotes this process, whereas enhanced serine phosphorylation, e.g. produced by
      cAMP, impairs the functional insertion of the receptors, rendering them unable to
      bind insulin.

PMID- 9002994
TI  - Adrenomedullin inhibits salt appetite.
AB  - Adrenomedullin (AM) exerts profound natriuretic and vasodilatory effects in
      conscious animals. This newly discovered hormone also acts in the central nervous
      system to inhibit water drinking and in the pituitary gland to reduce basal and
      stimulated ACTH release. We investigated whether the natriuretic action of AM in
      kidney was matched by a central nervous system action to decrease salt intake.
      Isotonic hypovolemia induced in male rats by pretreatment with polyethylene
      glycol potently stimulates both water and salt water (0.3 mol/liter NaCl)
      drinking. Saline drinking was significantly inhibited when AM was administered
      into the lateral cerebroventricle before the drinking interval. The effect was
      dose related (dose range, 44-88 pmol), long lasting (> 5 h), and reversible
      (resolved at 24 h). When hypovolemic rats were administered antiserum to AM
      (intracerebroventricular administration) before the drinking interval, a
      significant 2-fold augmentation of saline drinking was observed. These data
      suggest that in addition to peripheral actions on cardiovascular and renal
      function and pituitary actions to inhibit ACTH release, AM may act within the
      central nervous system to determine fluid and electrolyte balance and,
      ultimately, blood pressure.

PMID- 9002995
TI  - Identification of the peptides that inhibit the stimulation of thyrotropin
      receptor by Graves' immunoglobulin G from peptide libraries.
AB  - Graves' disease is characterized by the overproduction of thyroid hormones due to
      the persistent stimulation of TSH receptor by autoantibodies. To determine the
      epitopes recognized by the autoantibodies, an enzyme-linked immunosorbent assay
      was developed that uses the human TSH receptor extracellular domain attached to
      plastic wells. The total IgG from some of the Graves' patients interacted with
      the bound TSH receptor (TSHR) at a significantly higher level than that in normal
      individuals. The IgG preparation that showed the highest binding activity was
      used for the identification of peptide sequences that prevent binding of Graves'
      IgG to TSHR from positional scanning synthetic peptide combinatorial libraries. A
      hexapeptide mixture, X1X2FDDA (X1 is a mixture of E, M, and Y; X2 is a mixture of
      E, H, and T), was found to be effective for inhibiting the binding of Graves' IgG
      to the TSHR. Further fractionation of X1X2FDDA showed that the following three
      sequences were highly effective: EEFDDA, ETFDDA, and EHFDDA. The second position
      of the three peptides did not appear to be important. The peptides also inhibited
      the cAMP synthesis induced by IgG of four of eight patients with Graves' disease
      tested. The synthesis of cAMP by TSH was also inhibited by the peptides to some
      extent. The peptide sequences most likely mimic a part of the conformational
      epitopes recognized by at least one class of Graves' IgG.

PMID- 9002996
TI  - Melatonin action and signal transduction in the rat suprachiasmatic circadian
      clock: activation of protein kinase C at dusk and dawn.
AB  - Nocturnal synthesis of the pineal hormone melatonin (MEL) is regulated by the
      circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. We
      examined the hypothesis that MEL can feed back to regulate the SCN using a brain
      slice preparation from rat. We monitored the SCN ensemble firing rate and found
      that MEL advanced the time of peak firing rate by more than 3 h at restricted
      circadian times (CTs) near subjective dusk [CT 10-14 (10-14 h after lights on)]
      and dawn (CT 23-0) on days 2 and 3 after treatment. The effect of MEL at CT 10
      was blocked by pertussis toxin. The protein kinase C (PKC) activator, 12-O
      tetradecanoylphorbol 13-acetate, reset the SCN firing rate rhythm with a profile
      of temporal sensitivity congruent with that of MEL. Two specific PKC inhibitors,
      calphostin C and chelerythrine chloride, independently blocked MEL-induced phase
      advances at each sensitive period. Furthermore, MEL administration increased PKC
      phosphotransferase activity transiently to 200% at CT 10 and CT 23, but not at CT
      6. These data demonstrate that 1) MEL can directly modulate the circadian timing
      of the SCN within two windows of sensitivity corresponding to dusk and dawn; and
      2) MEL alters SCN cellular function via a pertussis toxin-sensitive G protein
      pathway that activates PKC.

PMID- 9002998
TI  - Cloning and expression of a 5'-iodothyronine deiodinase from the liver of
      Fundulus heteroclitus.
AB  - Recent molecular cloning studies in mammals and amphibians have demonstrated that
      the types I, II, and III deiodinases constitute a family of selenoproteins of
      critical importance in metabolizing T4 to active (i.e. T3) and inactive (i.e.
      rT3) metabolites. In several tissues of teleost fish, various deiodinase
      processes have been described, but the structural and functional characteristics
      of these enzymes and their relationship to the deiodinases present in higher
      vertebrates remains uncertain. Using a complementary DNA library derived from the
      liver of the teleost Fundulus heteroclitus, we have identified a complementary
      DNA that codes for a deiodinase with functional characteristics virtually
      identical to those of the mammalian and amphibian type II deiodinase. Sequence
      analysis demonstrates a high degree of homology at both the nucleotide and
      predicted amino acid levels between the Fundulus clone and these previously
      characterized type II enzymes, including the presence of an in-frame TGA codon
      that codes for selenocysteine. These findings demonstrate that the deiodinase
      family of selenoproteins has been highly conserved during vertebrate evolution
      and underscores their importance in the regulation of thyroid hormone action.

PMID- 9002997
TI  - Transient stimulation of myelin basic protein gene expression in differentiating
      cultured oligodendrocytes: a model for 3,5,3'-triiodothyronine-induced brain
      development.
AB  - We compared the regulation of myelin basic protein (MBP) gene expression by T3 in
      differentiating oligodendrocytes in culture with that previously observed by us
      in the neonatal rat brain. As in intact brain, expression of the T3R alpha gene
      preceded that of the T3R beta gene. Although the absence of T3 retarded the rate
      of accumulation of MBP messenger RNA, the level ultimately attained was similar
      to that reached in the presence of T3. This relationship mirrored the pattern
      observed in the neonatal brain. Transient transfection experiments showed that T3
      regulates MBP expression at the transcriptional level, but only for a limited
      period during differentiation. These observations imply that the early rise of
      MBP messenger RNA is T3 dependent, whereas the terminal levels are maintained
      independently of T3. Both the T3-dependent and, surprisingly, the T3-independent
      expression of MBP require the presence of an intact T3 response element. T3
      receptor may regulate MBP expression in a ligand-independent manner, or a nuclear
      factor other than T3 receptor may bind to the T3 response element of MBP to
      regulate terminal gene expression. These findings support the use of
      differentiating oligodendrocytes as a model of T3-induced brain development.

PMID- 9002999
TI  - The interaction between beta-endorphin and gonadal steroids in regulation of
      luteinizing hormone (LH) secretion and sex steroid regulation of LH and
      proopiomelanocortin peptide secretion by individual pituitary cells.
AB  - Reported studies using the conventional pituitary cell culture technique suggest
      that beta-endorphin (B-EP) produced locally in the pituitary or reaching it from
      the hypothalamus acts in conjunction with estradiol (E2) to initiate and in
      conjunction with progesterone (P4) to terminate the midcycle surge of LH. In
      addition, the reverse hemolytic plaque assay (RHPA) was used to investigate the
      effects of E2 and P4 on the secretory activity of individual pituitary cells. The
      results of these experiments indicate that 1) E2 enhances the secretion of LH,
      ACTH, and B-EP by individual pituitary cells; 2) E2 increases the number of
      secreting cells for each of the three hormones; 3) the rise in B-EP and ACTH
      secretion antecede that of LH; 4) P4 augments ACTH and B-EP secretion by
      individual pituitary cells; and 5) P4 has dual effects, acutely (1 h)
      potentiating LH secretion from already active cells and subsequently (8 h)
      recruiting cells that formerly had little or no secretory activities.
      Collectively, the above studies support a role for steroid hormones in regulation
      of midcycle LH secretion at the pituitary level. The results also suggest that
      intrapituitary (paracrine/autocrine) and extrapituitary (endocrine) B-EP
      modulates gonadal steroid effects on LH secretion by pituitary gonadotrophs.

PMID- 9003001
TI  - Role of basic-helix-loop-helix transcription factors in Sertoli cell
      differentiation: identification of an E-box response element in the transferrin
      promoter.
AB  - Sertoli cells are critical for testicular function and maintenance of the
      spermatogenic process. The induction of Sertoli cell differentiation in the
      embryo promotes testicular development and male sex determination. The
      progression of Sertoli cell differentiation during puberty promotes the onset of
      spermatogenesis. The maintenance of optimal Sertoli cell differentiation in the
      adult is required for spermatogenesis to proceed. The current study was designed
      to investigate the transcriptional regulation of Sertoli cell differentiation
      through the analysis of a previously identified marker of differentiation,
      transferrin gene expression. Sertoli cells produce transferrin to transport iron
      to developing spermatogenic cells sequestered within the blood-testis barrier.
      The transferrin promoter was characterized and found to contain two critical
      response elements, designated Sertoli element 1 (SE1) and Sertoli element 2
      (SE2). Through sequence analysis, SE2 was found to contain an E-box response
      element, which has been shown to respond to basic-helix-loop-helix (bHLH)
      transcription factors. The bHLH proteins are a class of transcription factors
      associated with the induction and progression of cell differentiation. bHLH
      proteins dimerize through the conserved helix-loop-helix region and bind DNA
      through the basic region. Nuclear extracts from Sertoli cells were found to cause
      an E-box gel shift when the cells were stimulated to differentiate in culture,
      but not under basal conditions. The SE2 gel shift of Sertoli nuclear extracts was
      competed with excess unlabeled SE2 or E-box DNA fragments. Several Sertoli
      nuclear proteins associate with the SE2 gel shifts, including 70-, 42-, and 25
      kDa proteins. Therefore, the critical SE2 element in the transferrin promoter is
      an E-box element capable of binding bHLH transcription factors. The ubiquitously
      expressed E12 bHLH protein dimerizes with numerous cell-specific bHLH factors. A
      Western blot analysis demonstrated that E12 was present in Sertoli cell nuclear
      extracts and associated with the SE2 gel shift. A ligand blot of Sertoli cell
      nuclear extracts with radiolabeled E12 had apparent bHLH proteins when the cells
      were stimulated to differentiate. The E-box sequence in the SE2 fragment of the
      transferrin promoter was CATCTG and was similar in gel shifts to the consensus E
      box elements (CANNTG) previously characterized. A bHLH inhibitory factor (Id)
      competed and inhibited formation of the Sertoli cell nuclear extract E-box gel
      shift. To extend this observation, Id protein was overexpressed in cultured
      Sertoli cells. A transferrin promoter chloramphenicol acetyltransferase construct
      was used to monitor Sertoli cell function. The presence of Id suppressed the
      activation of the promoter induced by Sertoli differentiation factors. Therefore,
      the inhibition of Sertoli bHLH factors by Id suppressed Sertoli cell
      differentiated function, as measured by transferrin expression. An E-box
      chloramphenicol acetyltransferase construct was also found to be active in
      Sertoli cells when cells were induced to differentiate. Screening the
      computerized nucleotide data bases demonstrated that putative E-box response
      elements are present in the promoters of a large number of Sertoli cell
      differentiated genes. In summary, a critical E-box response element has been
      identified in the transferrin promoter that can be activated by bHLH factors
      (e.g. E12) present in Sertoli cells. Inhibition of Sertoli bHLH factors by Id
      suppresses Sertoli cell differentiated function (i.e. transferrin expression),
      suggesting that bHLH transcription factors may be important in regulating Sertoli
      cell differentiated functions.

PMID- 9003000
TI  - Effects of retinol on activation of latent transforming growth factor-beta by
      isolated osteoclasts.
AB  - The multifunctional cytokine, transforming growth factor-beta (TGF beta), is
      found in many tissues in a latent or inactive form. The nature and composition of
      the latent complex can vary depending on tissue type. The release of active TGF
      beta from its latent complex is a potentially important mechanism for regulation
      of TGF beta activity. We have shown previously that osteoclasts activate latent
      TGF beta produced by bone and that bone cells produce a 100-kDa latent complex
      that lacks the latent TGF beta-binding protein. Here we investigated the effects
      of retinol on osteoclast activation of various forms of latent TGF beta. Two
      sources of osteoclasts were used that provide either mature avian osteoclasts or
      avian osteoclast precursors. Whereas both cell populations activate latent TGF
      beta, only mature osteoclasts respond to retinol with an increase in activation
      of latent TGF beta over basal levels. Activation could not be ascribed to pH
      changes in conditioned medium. Nonacid-dissociable 100-kDa latent complex, which
      is also produced by bone cells, was added to mature osteoclasts and to osteoclast
      precursors, but no activation was observed. Platelet latent TGF beta, which
      contains the 130-kDa latent TGF beta-binding protein, was activated by both
      osteoclast populations. Conditioned medium from the precursor population
      activated latent complex, whereas conditioned medium from mature cells did not.
      Activation of latent TGF beta by retinol-treated mature cells was not blocked by
      inhibitors of plasmin, nor was activation by conditioned medium from precursor
      cells. These data suggest that retinol-induced activation of latent TGF beta by
      osteoclasts is dependent on the stage of differentiation of these cells and the
      presence of other cell types, and that unlike other cell systems, the plasmin
      plasminogen activator mechanism is not involved.

PMID- 9003002
TI  - Inducible nitric oxide synthase in rat brown adipocytes: implications for blood
      flow to brown adipose tissue.
AB  - Exposure of rat brown adipocytes differentiated in culture to norepinephrine (NE)
      results in the production of nitrites (NO2-), the breakdown product of nitric
      oxide (NO). This production, which is blocked by actinomycin D1 is directly
      related to the duration of exposure to and dose of NE. Cytosol from NE-treated
      brown fat cells, but not from untreated cultures, catalyzed the Ca(2+)
      independent conversion of L-arginine to L-citrulline, which could be
      significantly blocked by the specific nitric oxide synthase (NOS) inhibitor NG
      nitro-L-arginine methyl ester. Reverse transcriptase-PCR demonstrates that the
      addition of NE; selective beta 1-, beta 2-, or beta 3-adrenergic receptor
      agonists; or agents increasing cAMP production, such as forskolin, to brown
      adipocytes stimulates inducible NOS (iNOS) messenger RNA, which is present within
      4 h after exposure. That iNOS is synthesized in brown fat cells is confirmed by
      immunoblotting using an antibody to the iNOS of mouse macrophages, Finally, in
      both brown adipose tissue (BAT) and brown adipocyte preparations from animals
      exposed to low temperature, iNOS messenger RNA and protein were expressed, and
      NOS activity was detectable; these findings were unlikely for room temperature
      acclimated rats. We conclude that brown fat cells can express an inducible form
      of NOS similar to the iNOS of macrophages, and that its production is directly
      dependent on sympathetic activity in physiological conditions. NO generated by
      stimulation of iNOS in brown adipocytes may represent an important mechanism to
      modulate different BAT functions, among which is vasodilation of the BAT
      microcirculation.

PMID- 9003004
TI  - Comparative study between normal rat chromaffin and PC12 rat pheochromocytoma
      cells: production and effects of corticotropin-releasing hormone.
AB  - The adrenal medulla of several species and some human pheochromocytomas contain
      CRH. The first aim of the present work was to find out whether normal rat adrenal
      chromaffin cells and the PC12 rat pheochromocytoma cell line produce CRH in vitro
      and what regulates its production. CRH was measured and characterized in the
      media of both types of chromaffin cells under basal conditions and after exposure
      to K+, nicotine, interleukin-1 beta, and nerve growth factor (NGF). The second
      aim was to examine the biological effect of exogenous CRH (and of its antagonist)
      on the production of catecholamines from these two types of cells. Our results
      are as follows: 1) Both types of chromaffin cells contained and secreted
      comparable amounts of immunoreactive-CRH under basal conditions and after K(+)
      induced depolarization, nicotine, and interleukin-1 beta; 2) the physicochemical
      characteristics of the immunoreactive-CRH in the cells and the media were
      identical to the putative CRH peptide on both sieve chromatography and RP-HPLC;
      3) synthetic CRH induced the production of catecholamines from both cell types in
      a dose- and time-dependent manner; this effect was abolished by the antagonist,
      alpha helical CRH; 4) exposure of PC12 cells to NGF (for 1 week) resulted in
      their neuronal differentiation and the stimulation of their production of CRH by
      30 times and of dopamine by 10 times, compared with parallel controls; this
      effect of NGF was abolished by alpha helical CRH. In conclusion, our data suggest
      that the production of CRH by PC12 cells represents the preservation of a normal
      chromaffin cell characteristic rather than a tumor-induced ectopic phenomenon.

PMID- 9003003
TI  - Role of insulin-like growth factor binding protein-2 and its limited proteolysis
      in neuroblastoma cell proliferation: modulation by transforming growth factor
      beta and retinoic acid.
AB  - Insulin-like growth factor (IGF) binding proteins (IGFBPs) modulate IGF action at
      cellular level through inhibition or, alternatively, potentiation, where their
      limited proteolysis is a contributory mechanism. Under basal conditions,
      neuroblastoma cells secrete IGFs (essentially IGF-II), IGFBPs (IGFBP-4 and
      predominantly IGFBP-2 that is partially proteolysed), and proteases, including
      tissue-type plasminogen (PLG) activator, whose activity is inhibited by PLG
      activator inhibitor-1. Neuroblastoma cells were used to investigate the influence
      of the plasmin system, transforming growth factor-beta retinoic acid on cell
      growth and the IGF system. In cells treated with 5 micrograms/ml PLG,
      proliferation was stimulated, an effect that was inhibited in the presence of
      either alpha IR-3 (which blocks the type 1 IGF receptor) or anti-IGF-II
      antibodies. There was a parallel increase in IGFBP-2 proteolysis, which resulted
      in a 5-fold loss of affinity for IGF-II. In the presence of 1 ng/ml transforming
      growth factor-beta, PLG-induced mitogenesis and IGFBP-2 proteolysis were reduced,
      and Northern blot analysis revealed increased PLG activator inhibitor-1 mRNA.
      Conversely, with 2 microM retinoic acid, the mitogenic effect of PLG, IGFBP-2
      proteolysis, and tissue-type PLG activator mRNAs were increased. Therefore, IGF
      II mediates autocrine proliferation in neuroblastoma cells under the control of
      IGFBPs secreted by the cells, its bioavailability being enhanced as a result of
      plasmin-induced IGFBP-2 proteolysis.

PMID- 9003005
TI  - Developmental and tissue-specific sulfonylurea receptor gene expression.
AB  - We have studied the developmental regulation of mouse sulfonylurea receptor (SUR)
      gene expression throughout several embryonic stages as well as in the adult
      mouse. To this end we used a 229-bp mouse complementary DNA corresponding to the
      3'-end of the SUR gene for in situ hybridization and solution
      hybridization/ribonuclease protection assays. We found that the SUR gene was
      expressed as early as embryonic day 12 in the developing pancreas, heart, and
      central nervous system. These tissues maintained significant levels of SUR
      messenger RNA (mRNA) throughout development. In addition, SUR mRNA was detected
      in the submandibular gland, anterior duodenum, dorsal root ganglia, lens, retina,
      and vibrissae by late developmental stages. SUR mRNA is widely distributed in
      adult mouse tissues, with the exception of the liver. In the adult pancreas, the
      SUR gene was expressed exclusively in endocrine tissue. Although significant
      levels of SUR mRNA were broadly seen throughout the brain, neurons of the
      cerebellum, hippocampus, and thalamus had especially high levels of SUR mRNA.
      These findings support the idea that the SUR has important functions in many
      other tissues in addition to the islets of the pancreas.

PMID- 9003006
TI  - Breed differences in expression of inhibin/activin subunits in porcine anterior
      pituitary glands.
AB  - Chinese Meishan (MS) boars have greater plasma FSH concentrations than European
      White Composite boars, but this difference does not occur in females of these
      breeds. To understand this disparity, we studied expression of the follistatin
      gene and of genes for the inhibin/activin alpha-, beta A-, and beta B-subunits in
      porcine anterior pituitary glands using quantitative reverse transcription-PCR
      and ribonuclease protection techniques. We found that 1) the inhibin/activin beta
      A- and beta B-subunits and follistatin were expressed in porcine pituitary, 2)
      the alpha-subunit was not detected in the porcine pituitary, but was highly
      expressed in porcine follicles; and 3) the beta B-subunit gene is more abundantly
      expressed (2-fold greater) in MS boar pituitaries than in pituitaries of White
      Composite boars. We conclude that this is not due to a breed difference, because
      the expression levels of this gene were similar in pituitaries of females of
      these breeds. No breed differences were detected for other genes screened in this
      study. From these observations, we propose that activin B, a dimer of beta B
      subunits and a stimulator of FSH secretion, may be partially responsible for the
      elevated plasma FSH concentrations in MS boars, and intrapituitary inhibin plays
      no or a very minimal role.

PMID- 9003007
TI  - Thyroid hormone-induced expression of specific somatostatin receptor subtypes
      correlates with involution of the TtT-97 murine thyrotrope tumor.
AB  - Following the protracted hypothyroid state, treatment with thyroid hormone will
      induce a decline in TSH and reduce thyrotrope hyperplasia. Somatostatin is a
      hypothalamic peptide that has been implicated in the negative regulation of TSH
      secretion in the thyrotrope. Moreover, analogs of native somatostatin have potent
      TSH-reducing and growth-retarding effects on human thyrotropinomas. The TtT-97
      tumor is an in vivo murine thyrotropic model that has retained its physiological
      response to thyroid hormone. This study investigates the regulation of
      somatostatin receptor subtypes in this tumor. TtT-97 tumors, actively growing in
      hypothyroid mice, did not express any significant somatostatin receptor messenger
      RNA (mRNA) or protein. T4 administration resulted in a reduction in TSH beta mRNA
      expression and a marked degree of tumor involution. Analysis of residual tumors
      from thyroid hormone-treated mice showed the specific up-regulation of SSTR1 and
      SSTR5 mRNA subtypes and the appearance of abundant, high affinity SSTR receptor
      binding sites within the tumor. Thus, the TtT-97 tumor provides a thyrotrope
      specific model in which to study the regulation of somatostatin receptor subtypes
      by thyroid hormone and correlate this expression with both antisecretory and
      antiproliferative effects.

PMID- 9003008
TI  - Angiotensin II receptor subtypes AT1 and AT2 are down-regulated by angiotensin II
      through AT1 receptor by different mechanisms.
AB  - The regulatory effects of angiotensin II (AngII) on its receptor subtypes, AT1
      and AT2, were studied using cultured bovine adrenal cells (BAC), which express
      both receptor subtypes, and PC12W and R3T3 cells, which express only AT2
      receptors. In BAC, AngII caused a decrease in AT1- and AT2-binding sites and
      their corresponding messenger RNAs (mRNAs), but with different kinetics. AT1
      binding sites decreased by more than 50% within the first 3 h, whereas AT1 mRNA
      started to decline after a lag period of 3 h. Both AT2-binding sites and mRNA
      remained stable within the first 6 h of AngII treatment. Then, AT2 mRNA decreased
      rapidly with an apparent half-life of 2-3 h, whereas AT2-binding sites declined
      with an apparent half-life of about 16 h. Measurement of transcription rate and
      mRNA half-life by the [3H]uridine-thiouridine method revealed that AngII reduced
      by 90% the rate of AT1 transcription, but had no effect on AT1 mRNA half-life,
      whereas it slightly reduced AT2 transcription, but markedly reduced AT2 mRNA
      stability. All of the effects of AngII on both AT1 and AT2 receptors were blocked
      by losartan, indicating that they were mediated exclusively through the AT1
      receptor. In PC12W cells, AngII was unable to modify AT2-binding sites or mRNA.
      Moreover, in BAC, [125I]AngII was internalized through the AT1 receptor, whereas
      occupancy of AT2 receptors in either BAC or PC12W did not produce internalization
      of the hormone. These results indicate that AngII, through the AT1 receptor, down
      regulates both AT1 and AT2, but by different mechanisms; AT1 receptor is
      regulated through internalization-degradation of the occupied receptor and
      inhibition of transcription, whereas AT2 receptor is regulated mainly by
      decreasing the stability of its mRNA. Moreover, the phorbol ester phorbol 12
      myristate 13-acetate mimicked most of the effects of AngII in BAC and decreased
      both AT2-binding sites and mRNA on PC12W cells, indicating that the hormonal
      regulation of both AT1 and AT2 receptors is mediated through protein kinase C
      activation.

PMID- 9003009
TI  - Fasting prevents experimental murine colitis produced by dextran sulfate sodium
      and decreases interleukin-1 beta and insulin-like growth factor I messenger
      ribonucleic acid.
AB  - Cytokines and insulin-like growth factors (IGFs) are involved in the induction
      and/or perpetuation of inflammatory bowel disease. The effect of fasting on
      inflammatory bowel disease was studied in a mouse experimental model of acute
      colitis caused by adding dextran sulfate sodium (DSS) to drinking water. Animals
      were either fed ad libitum or fasted (water only) for 2 days before death.
      Inflammation and tissue damage, measured as a colitis activity score, were
      markedly reduced in fasted (2.4 +/- 0.1) compared to fed (5.3 +/- 0.1) DSS
      animals (P < 0.0001). Colon interleukin-1 beta (IL-1 beta), IGF-I, and tumor
      necrosis factor-alpha messenger RNAs (mRNAs) were quantified by Northern blot
      hybridization and expressed as a percentage of mRNA abundance in fed controls. In
      DSS mice, IL-1 beta mRNA was elevated in the fed group (954 +/- 155%; P < 0.001),
      but was suppressed in fasted animals (71.1 +/- 11%). IGF-I mRNA also was elevated
      in fed DSS mice (421 +/- 71%; P < 0.01). This increase was attenuated in fasted
      DSS mice (202 +/- 17%; P < 0.01 compared to fed DSS mice). Tumor necrosis factor
      alpha mRNA was increased in fed DSS mice (162 +/- 15%; P < 0.01), but was not
      significantly lower in fasted animals. By in situ hybridization, IL-1 beta mRNA
      was localized to the lamina propria of colonic mucosa in fed DSS animals, but was
      not detectable in other groups. We conclude that fasting has a protective effect
      on the progression of acute DSS, induced colitis. This is associated with
      decreased expression of IL-1 beta and IGF-I mRNAs in the colon.

PMID- 9003010
TI  - Roles of insulin receptor substrate-1 and Shc on insulin-like growth factor I
      receptor signaling in early passages of cultured human fibroblasts.
AB  - Insulin-like growth factor-I (IGF-I) improves glucose metabolism and growth in
      patients with leprechaunism. We investigated signal transduction through IGF-I
      receptor in comparison with epidermal growth factor (EGF) receptor in early
      passages of cultured skin fibroblasts from a normal subject and a patient with
      leprechaunism whose insulin receptor tyrosine kinase was almost nonexistent.
      Insulin receptor substrate-1 (IRS-1) became tyrosine-phosphorylated and bound
      growth factor receptor-bound protein 2 (GRB2) quickly by IGF-I. The association
      of Shc with GRB2 by IGF-I was detected by immunoblot with anti-Shc antibody but
      was hardly visible with antiphosphotyrosine antibody, which was in marked
      contrast to efficient tyrosine phosphorylation of Shc by EGF. However, the
      potency of IGF-I for DNA synthesis was far stronger than EGF, which was not
      parallel with the potency of these growth factors to activate Shc or MAP kinase.
      Rather, phosphatidylinositol (PI) 3-kinase activity, which was activated by IGF-I
      about 5- to 10-fold more strongly than EGF, appeared to correlate with
      mitogenesis. Signal transduction pathways following IGF-I receptor or EGF
      receptor activation were indistinguishable between the normal subject and the
      patient. Our results strongly suggest that in human skin fibroblasts, which
      represent a more physiological cell culture: 1) IRS-1, rather than Shc, is the
      major tyrosine-phosphorylated protein binding GRB2 in initial phase of IGF-I
      signaling; 2) mitogenic potency of receptor tyrosine kinases such as IGF-I
      receptor and EGF receptor may not be determined solely by the amount of Shc-GRB2
      complex or the activity of MAP kinase; and 3) in contrast to previous reports,
      IGF-I and EGF receptor signalings are not defective in leprechaunism.

PMID- 9003011
TI  - Two signaling pathways, from the upper glycolytic flux and from the mitochondria,
      converge to potentiate insulin release.
AB  - In the rat pancreatic beta cell, low concentrations of glucose potentiate D
      glyceraldehyde (GA)-induced insulin release without any potentiation of the
      triose-induced elevation of cytosolic free Ca2+ concentration. Namely, 2-3 mM
      glucose strongly potentiates 5 mM GA-induced insulin release, and the combination
      of stimulatory concentration of glucose (10 mM) and 5 mM GA elicits far more than
      additive insulin release: this glucose action is independent of ATP-sensitive K+
      channel closure because it can be seen in the presence of diazoxide, an opener of
      the K+ channel. The triose-induced elevation of cytosolic free Ca2+ concentration
      was not potentiated by the presence of 3 mM glucose, and oxidation of labeled GA
      by the islet cells was not enhanced by the presence of glucose. The glucose
      action can be mimicked by mannose, but not by galactose, and was suppressed by
      inhibition of glucose phosphorylation with mannoheptulose or 2-deoxyglucose.
      Glucose also potentiates 2-ketoisocaproate-induced insulin release. In contrast,
      a combination of GA and 2-ketoisocaproate elicits only additive insulin release.
      Strikingly, 3 mM glucose does not potentiate insulin release in response to a
      depolarizing concentration of K+. Therefore, at least two signal pathways, one
      from upper glycolytic flux and one from mitochondrial metabolism, must converge
      to provide the potentiation of insulin release. We conclude that the upper
      glycolytic flux, acting at a site unrelated to the elevation of cytosolic free
      Ca2+, potentiates insulin release triggered by triose and mitochondrial fuels.

PMID- 9003012
TI  - Central lactogenic regulation of maternal behavior in rats: steroid dependence,
      hormone specificity, and behavioral potencies of rat prolactin and rat placental
      lactogen I.
AB  - Adult virgin female rats display maternal behavior when continuously exposed to
      foster young for 5-6 days. Central infusions of PRL or placental lactogens (PLs)
      together with systemic treatment of progesterone (P) and estradiol (E2) stimulate
      maternal behavior in 1-2 days. In the present set of studies, it was asked
      whether the actions of lactogenic hormones are dependent upon both E2 and P and
      specific to lactogenic molecules. Moreover, we wanted to know whether central
      infusions of rat (r) PRL and PLs were equally effective in inducing maternal
      behavior. In the first study, adult virgin rats were ovariectomized (ovx) and
      stereotaxically fitted with bilateral cannulas directed at the medial preoptic
      area (MPOA). Rats were then assigned to one of four groups: P plus E2, blank (B)
      plus E2, P plus B, and B plus B. P-filled or B capsules were implanted sc on
      treatment day 1 and removed on day 11, whereas E2 or B capsules were implanted on
      day 11. All groups were infused with rPRL (40 ng/side) five times from days 11-13
      and injected with bromocriptine (CB-154) sc (days 11-17) to suppress endogenous
      PRL release. Behavioral testing was conducted daily from days 12-17. It was found
      that exposure to both P and E2 was necessary to induce a fast onset of maternal
      behavior in PRL-infused females; priming with P or E2 alone in PRL-treated rats
      failed to stimulate a fast onset of behavior relative to that in nonsteroid
      treated controls. In the second experiment to determine the biochemical
      specificity of PRL's action, adult nulliparous rats were ovx, implanted with
      bilateral cannulas directed at the MPOA, treated with both P and E2, injected
      with CB-154, and infused centrally (five times) with 40 ng (per side) of bovine
      GH, ovine LH, or vehicle. Central infusions of either bovine GH or ovine LH
      failed to stimulate maternal behavior, suggesting that the stimulatory actions of
      PRL are related to its lactogenic properties. In the final study, rats were ovx,
      fitted with bilateral cannulas directed at the MPOA; treated with P, E2, and CB
      154; and given a single set of bilateral infusions of rPL-I or rPRL (40
      ng/side.infusion) on day 11, three sets of infusions of rPL-I or rPRL (days 11
      and 12), or vehicle infusions. Rats given three infusions of rPL-I and rPRL
      responded faster than controls, although the effect was not as robust as that in
      animals given five infusions in the initial study. rPL-I and rPRL groups did not
      differ from one another. Together these studies indicate that 1) both P and E2
      are required for lactogenic stimulation of maternal behavior; 2) the stimulatory
      actions of PRL and rPLs on maternal behavior are related to their lactogenic
      properties; 3) extended treatment of females with lactogenic hormones is more
      effective in stimulating the onset of maternal behavior; and 4) the neural
      potencies of rPRL and rPL-I are similar. These findings provide support for the
      idea that the induction of maternal behavior is stimulated by the central actions
      of lactogenic hormones.

PMID- 9003013
TI  - Thyroid hormones regulate the onset of osmotic activity of rat liver mitochondria
      after birth.
AB  - The effect of thyroid hormone deprivation on the osmotic activity of liver
      mitochondria from early newborn rats was studied. Experimentally induced
      hypothyroidism prevented the increase in the osmotic activity of mitochondria
      observed immediately after birth. Osmotic activity was restored by T4 and T3
      treatment to hypothyroid newborns but not when this treatment was supplemented
      with cycloheximide. Under the same circumstances, streptomycin had no effect.
      Hypothyroidism abolished the change in the slope of the osmotic curve (plot of
      inverse absorbance of mitochondrial suspensions incubated in sucrose solutions
      vs. inverse sucrose concentration) observed in mitochondria from euthyroid
      newborns at 110-120 mOsm sucrose, suggesting that hypothyroidism prevents the
      formation of tight physical connections between mitochondrial outer and inner
      membranes. Thyroid hormone deprivation increased the passive permeability of the
      mitochondrial inner membrane to protons, resulting in a decreased respiratory
      control ratio. Hypothyroidism prevented the sharp decrease in the affinity of
      mitochondria for ATP observed in euthyroid newborns immediately after birth.
      These results corroborate our previous suggestion (Endocrinology, 1995, 136:4448)
      that, during the early neonatal period, thyroid hormones control the synthesis of
      some nucleus-coded protein(s) involved in the assembly of F0,F1-ATPase.

PMID- 9003014
TI  - Induction of c-fos messenger ribonucleic acid in neuropeptide Y and growth
      hormone (GH)-releasing factor neurons in the rat arcuate nucleus following
      systemic injection of the GH secretagogue, GH-releasing peptide-6.
AB  - In this study we investigated the neurochemical identity of the arcuate cells
      activated following GH-releasing peptide-6 (GHRP-6) injection by comparing, on
      consecutive sections, the distribution c-fos messenger RNA (mRNA) with that of
      mRNAs for peptides synthesized in arcuate cells, including neuropeptide Y (NPY),
      GH-releasing factor (GRF), tyrosine hydroxylase, POMC, and somatostatin. Rats
      bearing chronically implanted jugular catheters were injected with either 50
      micrograms GHRP-6 or vehicle. Thirty minutes later they were terminally
      anesthetized and perfused with fixative. Paraffin-embedded sections of 7 microns
      thickness were processed using in situ hybridization for either c-fos mRNA or
      mRNAs for the neurochemical markers. In GHRP-6-treated rats the mean (+/-SEM)
      number of cells expressing c-fos mRNA in the arcuate nucleus (23 +/- 2
      cells/section per rat; n = 5) was significantly higher than for vehicle-treated
      controls (2 +/- 1 cells/section per rat; n = 5; P < 0.001, Mann-Whitney U test).
      Superimposed camera lucida maps indicated that, in GHRP-6-injected rats,
      neurochemically identifiable cells expressing c-fos mRNA also express NPY mRNA
      (51 +/- 4%), GRF mRNA (23 +/- 1%) tyrosine hydroxylase mRNA (11 +/- 3%), POMC
      mRNA (11 +/- 2%), or somatostatin mRNA (4 +/- 1%). Thus, the majority of cells
      expressing c-fos mRNA following GHRP-6 injection are NPY and GRF-containing
      cells.

PMID- 9003015
TI  - Gonadal steroids target AMPA glutamate receptor-containing neurons in the rat
      hypothalamus, septum and amygdala: a morphological and biochemical study.
AB  - Interactions between glutamate and gonadal steroids are involved in the
      regulation of limbic and hypothalamic functions. We hypothesized that hormonal
      signals affect excitatory neurotransmission by regulating the expression of
      glutamate receptors (GluR) in limbic and hypothalamic regions. To test this
      hypothesis, first, the coexpression of dl-alpha-amino-3-hydroxy-5-methyl-4
      isoxazone-propionate (AMPA) GluR1, GluR2/3, and androgen receptors or estrogen
      receptors was revealed in the same cells of septal, amygdaloid, and hypothalamic
      areas by double immunocytochemistry. The highest incidence of co-localization was
      detected in hypothalamic regions. To demonstrate a regulatory role of
      testosterone or estradiol on AMPA receptor expression, the hormonal milieu of
      male and female rats was manipulated by gonadectomy and hormonal treatment. GluR1
      and GluR2/3 expression was assessed by Western blots. Statistical analysis
      demonstrated that testosterone and estradiol have a stimulatory influence on the
      expression of AMPA receptors in the hypothalamus. The regulatory effect of
      estradiol on AMPA receptors was found to be site and gender specific: after
      estradiol treatment, samples taken from the hypothalamus contained increased
      levels of GluR1 and GluR2/3, whereas in the septum, bed nucleus and amygdala, no
      changes could be detected. Furthermore, the increase in hypothalamic GluR 2/3
      levels was two times higher in females, compared with males, whereas the changes
      in hypothalamic GluR 1 levels showed no sex differences. Our results support the
      hypothesis that the interaction between gonadal steroids and glutamate involves
      hormone regulation of GluR. This mechanism seems to be gender and site specific,
      suggesting that excitatory neurotransmission and related physiological mechanisms
      also may be distinctly different in males and females.

PMID- 9003016
TI  - Mullerian inhibiting substance inhibits branching morphogenesis and induces
      apoptosis in fetal rat lung.
AB  - Mullerian inhibiting substance (MIS) is a glycoprotein hormone required for
      normal male reproductive tract development; it is presumed to signal through a
      heteromeric complex of type I and type II receptors. MIS exposure produces a
      paracrine-mediated regression of the embryonic Mullerian duct with histological
      changes consistent with apoptosis. MIS has also been shown to inhibit fetal lung
      development in vitro and in vivo, although the mechanism of this inhibition is
      unknown. The primordial lung and gonad are anatomically proximate on embryonic
      day 13.5, raising the possibility of a paracrine-mediated influence of MIS in
      male embryos on lung as well as MIS effecting dissolution of the Mullerian duct.
      We hypothesized that a negative regulatory event(s) might occur in the lung, as
      occurs in the duct, at the onset of MIS protein expression; thus, apoptosis and
      branching morphogenesis were studied in explanted fetal rat lungs incubated with
      proteolytically activated MIS. MIS exposure resulted in reduced total lung bud
      number as well as lung perimeter length. Explanted lungs exposed to MIS also
      exhibited numerous apoptotic bodies. To assess whether this MIS-induced
      phenomenon in lung might be mediated by the MIS type II receptor (MIS RII),
      reverse transcriptase-PCR performed on multiple fetal rat lung RNA samples using
      oligonucleotide primers designed from the 3'-untranslated region of rat MIS RII
      complementary DNA showed a product of the expected size that when sequenced was
      nearly identical to rat MIS RII. Northern blot analysis using polyadenylated
      fetal rat lung RNA and a 3'-MIS RII probe revealed a 2-kilobase transcript that
      was also seen in testicular messenger RNA. These studies show that the putative
      ligand binding receptor for MIS is expressed in embryonic lung, where MIS
      negatively modulates branching and activates apoptosis. We speculate that the
      mechanism of MIS-induced inhibition of lung development in the male fetus begins
      with MIS binding to the MIS RII, followed by a signaling cascade resulting in
      delayed airway branching temporally associated with enhanced apoptosis.

PMID- 9003017
TI  - Immunohistochemical localization of leptin and uncoupling protein in white and
      brown adipose tissue.
AB  - Leptin is synthesized exclusively by adipocytes and acts on the hypothalamus to
      regulate energy balance. Previous messenger RNA expression studies demonstrated
      that leptin is expressed in white adipocytes and also in brown adipose tissue,
      however expression in brown fat is markedly lower than in white fat. This
      suggests the possibility that leptin expression in brown adipose tissue is due to
      the presence of white adipocytes that reside within brown adipose tissue, and
      that brown adipocytes actually do not express leptin. To address this point, we
      performed immunohistochemistry on paraffin sections and studied leptin protein
      expression in different depots of white and brown fat of lean and obese (db/db)
      mice. To establish the cell type expressing leptin, we also assessed the size and
      organization of lipid droplets, the ultrastructural features of mitochondria, and
      the presence or absence of uncoupling protein, a brown fat-specific marker. In
      white adipose tissue of lean and obese (db/db) mice, leptin protein was expressed
      in adipocytes of various sizes (range examined: 19.67-200 microns), including
      adipocytes at the multilocular stage of differentiation. Leptin staining was more
      intense in some depots (retroperitoneal), and appeared to decrease with fasting.
      In brown adipose tissue of lean animals, multilocular uncoupling protein (UCP)
      positive brown adipocytes had typical brown mitochondria and were leptin
      negative, both in fed and fasted conditions. At the periphery of the
      interscapular brown adipose tissue depot, unilocular, UCP-negative adipocytes
      (mean diameter: 41.55 microns) with white-type mitochondria were observed, and
      these cells were leptin-positive. In obese (db/db) animals, brown fat was
      composed mainly of small unilocular, UCP-positive. adipocytes (mean diameter:
      40.08 microns), which were also leptin-positive. At the periphery of the organ,
      numerous large, unilocular, UCP-negative adipocytes (mean diameter: 73.65
      microns) with white-like mitochondria were present. As expected, these cells were
      also leptin-positive. In summary, classical brown adipocytes differ from white
      adipocytes, not only by their morphology and UCP expression, but also by their
      apparent lack of detectable leptin expression. db/db brown adipocytes, however,
      were unilocular and leptin-positive. The molecular mechanisms mediating
      expression of leptin in white but not brown adipocytes of lean animals, and the
      significant expression of leptin in brown adipocytes of db/db mice will be the
      focus of future studies.

PMID- 9003018
TI  - 3,5,3'-Triiodo-L-thyronine potentiates all-trans-retinoic acid-induced apoptosis
      during differentiation of the promyeloleukemic cell HL-60.
AB  - Although the programmed cell death mediated by thyroid hormone is not well
      evaluated in mammalian cells, thyroid hormone plays a crucial role in
      differentiation of the cells during the metamorphosis of Xenopus, suggesting that
      thyroid hormone has the potential ability to induce the apoptosis. To investigate
      the thyroid hormone-inducible apoptosis, we cultured HL-60 cells with various
      amounts of all-transretinoic acid (RA) and L-T3. T3 alone did not induce the
      apoptosis of the cells. T3, however, suppressed the proliferation of cells in the
      presence of RA. DNA ladder and microscopical examination showed that the
      reduction of cell number was due to the apoptosis induced by RA. These findings
      suggested that T3 affects the apoptotic process during the differentiation of HL
      60 cells by RA. T3-inducible apoptosis may require the factors augmented by RA in
      HL-60 cells.

PMID- 9003019
TI  - In vivo resistance to glucocorticoid-induced apoptosis in rat thymocytes with
      normal steroid receptor function in vitro.
AB  - Previous studies have shown that although the majority of rat thymic lymphocytes
      are sensitive to glucocorticoid-induced apoptosis in vivo, a small population of
      mature thymic lymphocytes remains even after high dose steroid administration.
      Here, we describe experiments that were performed to understand the molecular
      basis of the resistance of these cells to glucocorticoid-induced apoptosis.
      Adrenalectomized rats were treated for 72 h with a bolus dose (5 mg/kg body
      weight) of dexamethasone to produce a population of thymocytes that survived
      glucocorticoid administration. Reinjection of these animals with equivalent doses
      of dexamethasone failed to induce further thymic regression or apoptosis in these
      cells. Glucocorticoid receptor number and receptor binding affinity for
      dexamethasone were similar in control and resistant thymocytes. Western blot
      analysis using epitope-purified antiglucocorticoid receptor antibodies confirmed
      this observation. To delineate the mechanism of resistance, we evaluated whether
      cells resistant to dexamethasone in vivo showed any response to this
      glucocorticoid in vitro. The ability of glucocorticoid to inhibit [3H]lysine
      incorporation into protein in cells treated with dexamethasone in vitro was
      equivalent to control cells, indicating that glucocorticoid receptor function was
      normal in both populations. To evaluate whether in vivo glucocorticoid-resistant
      thymocytes retain any capacity to undergo apoptosis, in vitro studies were
      performed on these cells using the calcium ionophore A23187 to induce programmed
      cell death. Cleavage of chromatin into 30- to 50-kilobase fragments or
      oligonucleosomal fragments characteristic of apoptosis was observed in both
      sensitive and resistant thymocytes treated in vitro with A23187. Cells resistant
      to glucocorticoid in vivo unexpectedly exhibited internucleosomal cleavage of
      chromatin and apoptosis in response to dexamethasone in vitro. We examined the
      levels of the apoptosis suppressor Bcl-2 in thymocytes isolated from control and
      72 h dexamethasone-treated rats to determine whether increased expression of this
      protein could explain the resistance to glucocorticoid-induced apoptosis that we
      observed. Both glucocorticoid-sensitive and -resistant thymocytes expressed
      similar levels of Bcl-2. Together, these data indicate that resistance to
      glucocorticoid in vivo is not due to alteration of the glucocorticoid receptor or
      to expression of Bcl-2, but rather to some endogenous thymic factor and/or cell
      to-cell contact that probably alters glucocorticoid receptor signaling.

PMID- 9003020
TI  - Regulation of glycosylphosphatidylinositol-specific phospholipase D secretion
      from beta TC3 cells.
AB  - Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is abundant in
      mammalian serum, but the source of the circulating enzyme is unknown. Pancreatic
      islets have been reported to contain and secrete GPI-PLD. In this report we
      examined the regulation of GPI-PLD secretion from beta TC3 cells, a mouse
      insulinoma cell line. In the absence of glucose, phorbol myristic acid (0.1
      microM) stimulated insulin secretion by 2.5-fold and GPI-PLD secretion by 2-fold.
      Carbachol (5 microM), glucagon-like peptide I-(7-36) amide (0.1 microM), and
      isobutylmethylxanthine (0.1 mM) had no significant effect on insulin or GPI-PLD
      secretion in the absence of glucose. Glucose (16.7 mM) stimulated both GPI-PLD
      and insulin secretion from beta TC3 cells by 55% and 235%, respectively. In
      addition, glucose potentiated the secretagogue effect of isobutylmethylxanthine,
      phorbol myristic acid, and glucagon-like peptide I on both insulin and GPI-PLD
      secretion. By immunohistochemistry and confocal microscopy, beta TC3 cells
      contain both insulin and GPI-PLD, which generally colocalized intracellularly.
      However, GPI-PLD secretion differed from insulin secretion by a higher rate of
      basal release (2.8% vs. 0.23%/h), a lower magnitude of response to secretagogues,
      and a more prolonged period of increased secretion. These results demonstrate
      that beta TC3 cells secrete GPI-PLD in response to insulin secretagogues and
      suggest that GPI-PLD may be secreted via the regulated pathway in these cells.

PMID- 9003021
TI  - Expression of thyrotropin-releasing hormone (TRH) receptor mRNA in somatotrophs
      in the rat anterior pituitary.
AB  - A response of growth hormone (GH) to thyrotropin-releasing hormone (TRH) is
      observed in lower mammals and patients with diseases such as a cromegaly, but not
      in normal subjects. We have previously demonstrated the existence of intact TRH
      receptor mRNA in GH-secreting adenoma. To examine whether intact somatotrophs in
      the anterior pituitary also express TRH receptor, we attempted to localize both
      TRHR mRNA and GH immunoreactivity simultaneously. In situ hybridization analysis
      revealed TRHR mRNAs specifically in the anterior pituitary, and 61.1% of the
      anterior pituitary cells expressed this transcript. Staining for GH and PRL on
      the same samples showed that the somatotrophs apparently expressed TRHR mRNA and
      approximately 62.3% and 30.9% of hybridization-positive cells were somatotorophs
      and mammotrophs, respectively. Moreover, TRHR mRNA level in the somatotrophs
      expressed as the number of silver grains per cell was equivalent to that in the
      mammotrophs. These findings demonstrated expression of the TRHR mRNA in
      somatotrophs in the rat anterior pituitary, and also showed that more than 50% of
      the TRHR mRNA detected in the anterior pituitary was derived from these cells.

PMID- 9003022
TI  - Evidence for a parathyroid hormone-2 receptor selective ligand in the
      hypothalamus.
AB  - The PTH2 receptor is expressed in several brain nuclei but we have been unable to
      detect mRNA encoding PTH, which is the only known ligand for the PTH2 receptor,
      in the brain. We now have evidence for a PTH2 receptor selective ligand in an
      acid-acetone extract made from bovine hypothalamus. The partially purified
      extract activates the PTH2 receptor more effectively than it activates the
      PTH/PTHrP receptor, while PTH activates these two receptors at similar
      concentration. The activity appears immunologically distinct from PTH and its
      effect is potently antagonized by [D-Trp12]bPTH(7-34). These data provide
      evidence for a biologically active peptide, which may be related to PTH, and
      which is a potential new neurotransmitter or hormone.

PMID- 9003023
TI  - Ca(2+)-regulated expression of aldosterone synthase is mediated by calmodulin and
      calmodulin-dependent protein kinases.
AB  - The chronic maintenance of aldosterone production in the adrenal zona glomerulosa
      is associated with increased expression of aldosterone synthase (P450aldo), the
      enzyme responsible for the conversion of 11-deoxycorticosterone to aldosterone.
      The major physiologic regulators of aldosterone production are angiotensin II
      (ANG II) and (K+) which act in part through increasing intracellular calcium
      ([Ca2+]i). Recently we demonstrated that increased [Ca2+]i is associated with K+
      induction of P450aldo expression. To determine whether Ca2+ regulation of
      P450aldo is mediated through calmodulin or calmodulin-dependent kinases (CaMK),
      we investigated the actions of calmidazolium (a calmodulin inhibitor) and KN93
      (an inhibitor of CaMK) on expression of P450aldo in human adrenocortical H295R
      cell line. Treatment with either calmidazolium or KN93 completely inhibited K(+)
      stimulated expression of P450aldo mRNA with little effect on ANG II or dibutyryl
      cyclic AMP-stimulated induction of this transcript. Cellular calcium levels were
      also increased using the calcium ionophore ionomycin and calcium channel agonist
      Bay K 8644. These compounds increased P450aldo mRNA and this calcium induction
      was inhibited by calmidazolium and KN93. These data show that K(+)-stimulated
      expression of P450aldo mRNA is regulated in a Ca2+ sensitive manner through
      mechanisms involving calmodulin and CaMK.

PMID- 9003024
TI  - Leptin activates neurons in ventrobasal hypothalamus and brainstem.
AB  - Leptin is a circulating protein secreted by adipocytes which has profound
      feeding, metabolic, and neuroendocrine effects. Leptin receptors have been
      localized to the hypothalamus, but the anatomic sites responsible for mediating
      the effects of circulating leptin have not been demonstrated. We report that
      systemic administration of leptin activates nuclear groups in the ventrobasal
      hypothalamus, including the ventromedial, dorsomedial, and ventral premammillary
      hypothalamic nuclei. Leptin also activated the parvicellular subdivisions of the
      paraventricular hypothalamic nucleus that project to parasympathetic and
      sympathetic preganglionic neurons. Finally, leptin administration activated the
      superior lateral parabrachial subnucleus, a nuclear group containing
      cholecystokinin neurons that project to the ventrobasal hypothalamus. These
      findings indicate that circulating leptin activates specific nuclear groups in
      the hypothalamus and brainstem known to regulate complex physiological responses
      during times of substrate availability.

PMID- 9003025
TI  - Potential role for a regulator of G protein signaling (RGS3) in gonadotropin
      releasing hormone (GnRH) stimulated desensitization.
AB  - The cellular and molecular mechanisms of gonadotrope desensitization are unknown
      but transduction of the GnRH signal is known to involve sequentially the GnRH
      receptor, Gq alpha protein, phospholipase C beta-1, inositol-1,4,5-trisphosphate
      (IP3), and intracellular Ca+2 release. Here, we report the results of studies of
      a new family of proteins known as regulators of G protein signaling (RGS) that
      recently have been implicated in desensitization of several ligand induced
      processes. Using DNA-mediated transfection, we co-expressed the GnRH receptor and
      RGS1,2,3, or 4 in COS-1 cells. Control cells and those expressing RGS1,2, and 4
      produced five fold increases in IP3 levels during the 30 sec after treatment with
      GnRH. In contrast, RGS3 expression suppressed by 75% the GnRH-induced IP3
      responses. RGS3 was shown to bind Gq alpha protein in a model in vitro system:
      recombinant RGS3-glutathione-S-transferase (GST) fusion protein bound five-fold
      more 35S-met labeled Gq alpha protein than did with GST alone, suggesting that
      the mechanism of RGS3 action is attenuation of Gq alpha protein activation of
      phospholipase C. RGS3 mRNA and protein were observed to be expressed endogenously
      in the gonadotropic alpha T3-1 cell line. These results suggest a potential role
      for RGS3 in modulating the LH secretory responsiveness of the pituitary
      gonadotrope to GnRH.

PMID- 9003026
TI  - Direct intraovarian effects of leptin: impairment of the synergistic action of
      insulin-like growth factor-I on follicle-stimulating hormone-dependent estradiol
      17 beta production by rat ovarian granulosa cells.
AB  - The Ob gene product, leptin, is secreted by adipocytes and is required for
      fertility in the mouse. Leptin-deficient mice are obese and infertile, symptoms
      reminiscent of polycystic ovary syndrome (PCOS). Prior studies have shown that
      serum leptin levels are elevated in a significant sub-population of anovulatory
      women with PCOS, suggesting that elevated leptin levels may adversely affect
      ovarian function. Since leptin receptor mRNA has been detected in the ovary, this
      study was designed to test the hypothesis that leptin may impair granulosa cell
      (GC) estradiol-17 beta (E2) production by a direct mechanism. GC were isolated
      from the ovaries of 26-day-old Sprague-Dawley rats, and were cultured (60,000
      GC/well) in 96-well plates in the presence and absence of ovine FSH (0.001-100
      ng/ml) and androstenedione (0.1 microM), with and without recombinant murine
      leptin (0.1-100 ng/ml) for 48 h. Leptin alone had no effect on E2 production. FSH
      caused a dose-related increase in E2 production by GC (ED50 = 1.9 +/- 0.4 ng/ml).
      Addition of leptin did not alter FSH-stimulated B2 levels. Concomitant treatment
      with FSH and IGF-I (30 ng/ml) augmented maximal FSH-dependent E2 production five
      fold. Leptin caused a dose-dependent (IC50 = 2.7 +/- 0.6 ng/ml) inhibition (30
      50%) of the IGF-I increase in FSH-stimulated E2 production. The inhibitory effect
      of leptin was specific for E2 production since there was no effect on basal, FSH
      , or FSH+ IGF-I-dependent progesterone levels. The results of this study
      demonstrate that leptin can directly impair the IGF-I-mediated augmentation of
      FSH-stimulated E2 synthesis by GC. These data raise the possibility that high
      leptin levels may contribute to infertility in some women with PCOS by
      counteracting the sensitizing effects of IGF-I in dominant follicles.

PMID- 9003027
TI  - Co-expression of bovine growth hormone (GH) and human GH antagonist genes in
      transgenic mice.
AB  - Bovine growth hormone (bGH) transgenic (Tg) mice have been shown to possess
      enhanced growth phenotypes and exhibit severe glomerulosclerosis. One amino acid
      substitution in GH, i.e. G119R in bGH or G120R in human (h) GH, results in GH
      antagonists (GHAs). GHA-Tg mice exhibit dwarf phenotypes and normal kidneys. In
      order to investigate the possibility of GHAs as pharmaceutical agents for the
      treatment of human diseases with excessive GH levels, we cross bred mice that
      express bGH with those that express hGHA. Double positive Tg mice were identified
      that express both genes although at different levels. Kidney histological studies
      revealed that the double positive Tg mice with high GHA/GH expression ratios
      possessed normal or near normal kidneys, whereas those with low GHA/GH ratios
      exhibited glomerulosclerosis similar to GH-Tg mice. Thus, co-expression of GH and
      GHA genes in vivo results in animal phenotypes and kidney histopathologies which
      are a reflection of the relative expression levels of each gene.

PMID- 9003029
TI  - Cyclic GMP-dependent protein kinase and cellular signaling in the nervous system.
AB  - Nitric oxide (NO) and natriuretic peptide hormones play key roles in a surprising
      number of neuronal functions, including learning and memory. Most data suggest
      that they exert converging actions by elevation of intracellular cyclic GMP
      (cGMP) levels through activation of soluble and particulate guanylyl cyclases.
      However, cGMP is only the starting point for multiple signaling cascades, which
      are now beginning to be defined. A primary action of elevated cGMP levels is the
      stimulation of cGMP-dependent protein kinase (PKG), the major intracellular
      receptor protein for cGMP, which phosphorylates substrate proteins to exert its
      actions. It has become increasingly clear that PKG mediates some of the neuronal
      effects of cGMP, but how is not yet clear. One clear illustration of this pathway
      has been reported in striatonigral nerve terminals, where NO mediates
      phosphorylation of the protein phosphatase regulator dopamine- and cyclic AMP
      regulated phosphoprotein having a molecular mass of 32,000 (DARPP-32) by PKG.
      There are remarkably few PKG substrates in brain whose identities are known. A
      survey of these proteins and those known from other tissues that might also be
      found in the nervous system reveals the key molecular sites where cGMP and PKG
      signaling is likely to be regulating neural function. These potential substrates
      are critically placed to have profound effects on the protein phosphorylation
      network through regulation of protein phosphatases, intracellular calcium levels,
      and the function of many ion channels and neurotransmitter receptors. The brain
      also contains a rich diversity of specific PKG substrates whose identities are
      not yet known. Their future identification will provide exciting new leads that
      will permit better understanding of the role of PKG signaling in both basic and
      higher orders of brain function.

PMID- 9003028
TI  - Leptin is a metabolic gate for the onset of puberty in the female rat.
AB  - The timing of puberty onset in mammals is tightly coupled to the animal's
      nutritional and metabolic state. We conducted two experiments to test the
      hypothesis that leptin acts as a metabolic signal for the onset of puberty. In
      the first experiment, we administered leptin (6.3 micrograms/g twice daily) to a
      group of normal prepubertal female rats and compared their rate of sexual
      maturation to that of two control groups. The group of leptin-treated animals and
      one group of control animals were allowed to eat ad lib, while the other group of
      control animals was pair-fed to the leptin-treated group. Food intake in the
      leptin-treated group was reduced to approximately 80% of the ad lib-fed control
      group, resulting in retarded growth in both leptin-treated and pair-fed animals.
      All measured indices of pubertal maturation-age at vaginal opening, age at first
      estrus, ovarian weight, ovulatory index (corpora lutea/ovarian section), uterine
      weight, and uterine cross-sectional area-were significantly delayed in the pair
      fed group but not different between the leptin-treated group and ad lib-fed
      controls. The second experiment was similar to the first, except that both the
      leptin-treated group and the pair-fed group were fed at 70% of the ad lib-fed
      controls. Under these conditions, leptin only partially reversed the delay in
      sexual maturation, as reflected by the age at vaginal opening and first estrus.
      These results suggest that leptin is not the primary signal that initiates the
      onset of puberty but that instead, it acts in a permissive fashion, as a
      metabolic gate, to allow pubertal maturation to proceed-if and when metabolic
      resources are deemed adequate; moreover, these observations suggest that other
      metabolic factors, besides leptin, influence the timing of puberty onset under
      conditions of more severe dietary stress.

PMID- 9003030
TI  - Rearrangement and reactivation of the myelin basic protein locus in myelin
      deficient (mld) mouse brain.
AB  - Myelin-deficient (mld) is a complex mutation affecting the myelin basic protein
      (MBP) locus of the mouse. It consists of duplication and partial inversion of the
      MBP gene and results in a dysfunctional MBP locus. The mutant phenotype is
      reversed, both in vivo and in vitro, in approximately 5% of mld oligodendrocytes.
      One possible mechanism for the somatic reversion is recombination between
      homologous sequences of the duplicated gene copies to reconstitute a functional
      MBP locus. There are several possible recombination events that could
      reconstitute a functional MBP locus by DNA rearrangement. Two of these would
      result in reinversion and circularization of specific MBP gene sequences,
      respectively. In this work polymerase chain reaction analysis was used to detect
      both reinverted and circularized MBP gene sequences in mld mouse tissues,
      indicating that DNA rearrangement at the MBP locus does occur. Analysis of
      individually harvested cells showed that in revertant MBP-positive mld
      oligodendrocytes DNA rearrangement at the MBP locus was correlated with
      reactivation of the MBP gene. Fluctuation analysis showed that reactivation of
      the MBP locus is a stochastic event occurring with a frequency of approximately
      1.4 x 10(-6) per cell per cell cycle during oligodendrocyte development. The
      frequency of rearrangement and reactivation of the MBP locus was comparable in
      double mutant (mld/mld, scid/scid) and single mutant (mld/mld, +scld/+scld) mice,
      indicating that the scid factor is not required for MBP gene reactivation in mld.
      The significance of DNA rearrangement in mammalian development is discussed.

PMID- 9003031
TI  - NMDA receptor heterogeneity during postnatal development of the rat brain:
      differential expression of the NR2A, NR2B, and NR2C subunit proteins.
AB  - Changes in the expression of the NMDA receptor subunits (NRs) NR2A, 2B, and 2C
      were investigated in histo blots of the developing rat brain with subunit
      specific antisera. At birth, the NR2B subunit was detected almost ubiquitously,
      the NR2A subunit staining was faint and restricted to the hippocampus, cerebral
      cortex, and striatum, and no NR2C subunit immunoreactivity was detected. During
      the first 3 postnatal weeks, the NR2B subunit became confined to forebrain
      structures, whereas the NR2A immunoreactivity became abundantly expressed
      throughout the brain. The NR2C immunoreactivity emerged 5 days after birth in the
      olfactory bulb, thalamus, and vestibular nuclei and became very intense after 10
      days in cerebellar granule cells, its primary site of expression in adulthood.
      After 3 weeks, NR2A and NR2B immunoreactivity decreased to adult levels, whereas
      NR2C immunoreactivity remained unchanged. The patterns of distribution of the
      subunit proteins were in agreement with those of their corresponding mRNAs, as
      monitored by in situ hybridization histochemistry, although the mRNA translation
      appeared to be delayed by several days in certain areas. Our results reveal a
      progressive increase in the heterogeneity of NMDA receptors due to the comparably
      late onset of NR2A and NR2C subunit expression and by the area-specific
      rearrangement of NR2B subunit expression following birth.

PMID- 9003032
TI  - A globular, not asymmetric, form of acetylcholinesterase is expressed in chick
      motor neurons: down-regulation toward maturity and after denervation.
AB  - In vertebrate neuromuscular junctions, the postsynaptic specializations include
      the accumulation of acetylcholinesterase (AChE) at the synaptic basal lamina and
      the muscle fiber. Several lines of evidence indicate that the presynaptic motor
      neuron is able to synthesize and secrete AChE at the neuromuscular junctions. By
      using anti-AChE catalytic subunit, anti-butyrylcholinesterase (BuChE) catalytic
      subunit, and anti-AChE collagenous tail monoclonal antibodies, we demonstrated
      that the motor neurons of chick spinal cord expressed AChE in vivo and the
      predominant AChE was the globular form of the enzyme. Neither asymmetric AChE nor
      BuChE was detected in the motor neurons. The molecular mass of AChE catalytic
      subunit in the motor neuron was approximately 105 kDa, which was similar to that
      of the globular enzyme from low-salt extracts of muscle; both of them were
      approximately 5 kDa smaller than the asymmetric AChE from high-salt extracts of
      muscle. The level of AChE expression in the motor neurons decreased, as found by
      immunochemical and enzymatic analysis, during the different stages of the chick's
      development and after nerve lesion. Thus, the AChE activity at the neuromuscular
      junctions that is contributed by the presynaptic motor neurons is primarily the
      globular, not the asymmetric, form of the enzyme, and these contributions
      decreased toward maturity and after denervation.

PMID- 9003033
TI  - Neuronal nicotinic acetylcholine receptors on bovine chromaffin cells: cloning,
      expression, and genomic organization of receptor subunits.
AB  - Neuronal nicotinic acetylcholine receptors from bovine adrenomedullary chromaffin
      cells play a primary role in triggering catecholamine secretion. In the present
      study, their constituent subunits were characterized. In addition to the alpha 3
      subunit, which we have previously cloned, the presence of alpha 5 and beta 4 but
      not of beta 2 subunits was detected by reverse transcription-PCR analysis of mRNA
      from adrenal medulla. In situ hybridization indicated that alpha 3, alpha 5, and
      beta 4 subunits are coexpressed in all chromaffin cells. The primary structure of
      alpha 5 and beta 4 subunits was determined and functional receptors were obtained
      upon coinjection of subunit cRNAs into Xenopus oocytes. In contrast to other beta
      4-containing nicotinic receptors, the ones formed by the bovine beta 4 subunit
      are insensitive to the agonist cytisine. Finally, we characterized the intergenic
      region of alpha 3 and alpha 5 subunits, which together with the beta 4 subunit,
      form a gene cluster in rats and chickens. RNase assays and the existence of
      overlapping cDNAs indicate that, in the bovine genome, the alpha 3 and alpha 5
      genes overlap at their 3' ends. This fact is probably due to inefficient
      transcription termination, as a result of weak polyadenylation signals.

PMID- 9003034
TI  - Differential expression of type I, II, and V adenylyl cyclase gene in the
      postnatal developing rat brain.
AB  - The developmental changes in the expression of mRNA encoding three major brain
      adenylyl cyclase (AC; EC 4.6.1.1) subtypes, type I (AC1), II (AC2), and V (AC5),
      were examined by in situ hybridization in rat brain from neonate to adult. During
      the early postnatal stage, levels of AC1 transcripts were very high in the
      cerebral cortex, striatum, thalamus, brainstem, and inferior colliculus. Then,
      AC1 mRNA levels rapidly decreased to the levels observed in the adult brain. In
      contrast, AC1 transcripts were very low at the early postnatal stage in the
      cerebellum and hippocampus and markedly increased during the second postnatal
      week. AC2 mRNA was widely distributed in rat brain throughout the development,
      and levels did not vary with different ages of the animal. AC5 mRNA was expressed
      to a limited extent in the neonatal brain, but levels dramatically increased
      during the second postnatal week in restricted regions, including the striatum,
      nucleus accumbens, and olfactory tubercle. The developing profiles of three AC
      gene transcripts were confirmed by northern blot analyses with mRNA isolated from
      different brain regions at different postnatal stages. In addition, the basal and
      forskolin-, GTP gamma S-, or Ca2+/calmodulin-stimulated AC activity in plasma
      membrane preparations obtained from different brain regions at different ages
      were correlated with the age-dependent changes in the region-specific AC mRNA
      levels. These results demonstrate that different AC subtypes are expressed in the
      developing rat brain in a region- and age-specific manner, suggesting specific
      roles not only in the synaptic transmission but also in the differentiation and
      maturation of neuronal cells in the developing brain.

PMID- 9003035
TI  - Biochemical evidence for the existence of a pool of unassembled C2 exon
      containing NR1 subunits of the mammalian forebrain NMDA receptor.
AB  - Optimum conditions were determined for the solubilisation of native NMDA
      receptors of adult mammalian brain with the retention of [3H]MK-801 radioligand
      binding activity. The most efficient conditions were 1% Triton X-100/1 M NaCl.
      The efficiency of solubilisation was as follows: cloned NMDA receptors expressed
      in mammalian cells > forebrain receptors > cerebellar receptors. Triton X-100/1 M
      NaCl-solubilised forebrain NMDA receptors had a molecular size of 710,000
      daltons, but significant NR1 immunoreactivity (41%) migrated as a monomer of
      125,000 daltons. Immunoaffinity purification of NMDA receptors from forebrain by
      anti-NR1 911-920 antibody affinity chromatography from 1% Triton X-100/1 M NaCl
      solubilised extracts yielded purification of the NR1 Mr 120,000 immunoreactive
      species, but no detectable NR2A or NR2B immunoreactivity. Immunoprecipitation of
      NMDA receptors from Triton X-100/1 M NaCl extracts with anti-NR1 911-920
      antibodies also resulted in precipitation of NR1 subunits, but with no detectable
      NR2A or NR2B subunits. In contrast, by immunoprecipitation with anti-NR1 17-35
      antibodies, which recognise all forms of NR1, NR1, NR2A, and NR2B
      immunoreactivities were detected in the immune pellets. Similarly, a co
      association of NR1, NR2A, and NR2B subunits was demonstrated following extraction
      of forebrain membranes with 1% sodium deoxycholate (pH 9) and purification by
      anti-NR1 911-920 antibody affinity chromatography. These results are consistent
      with the identification of a pool of unassembled C2 exon-containing NR1 subunits,
      i.e., NR1-1a, NR1-1b, NR1-2a, and NR1-2b, selectively solubilised by 1% Triton X
      100/1 M NaCl.

PMID- 9003036
TI  - Opioid effects on 45Ca2+ uptake and glutamate release in rat cerebral cortex in
      primary culture.
AB  - Primary cultures of rat cortex, conveniently prepared from newborn animals, were
      used to study opioid effects on 45Ca2+ uptake and glutamate release. 45Ca2+
      uptake, induced by treatment with glutamate or NMDA, was largely blocked by the
      NMDA antagonist MK-801. K+ depolarization-induced 45Ca2+ uptake was also reduced
      by MK-801, indicating that the effect was mediated by glutamate release. Direct
      analysis verified that glutamate, and aspartate, were indeed released. Opioid
      peptides of the prodynorphin system were also released and these, or other
      peptides, were functionally active, because naloxone treatment increased
      glutamate release, as well as the 45Ca2+ uptake induced by depolarization. Opioid
      agonists, selective for mu-, kappa-, and delta-receptors, inhibited the 45Ca2+
      uptake induced by K+ depolarization. The combination of low concentrations of MK
      801 and opioid agonists resulted in additive inhibition of K(+)-induced 45Ca2+
      uptake. The results indicate that this system may be useful as an in vitro CNS
      model for studying modulation by opioids of glutamate release and Ca2+ uptake
      under acute, and perhaps also chronic, opiate treatment.

PMID- 9003037
TI  - Interactions of muscarinic receptors with the heterotrimeric G proteins Gq and
      G12: transduction of proliferative signals.
AB  - The proliferative and transforming properties of m2 and m5 muscarinic
      acetylcholine receptors and a series of wild-type, chimeric, and mutant G
      proteins were measured alone or in combination in NIH 3T3 cells to determine
      which G proteins mediate these signals and to what extent these signals can be
      influenced by changing the stoichiometry of receptors and G proteins. Responses
      were measured using the focus-forming assay and a novel assay called R-SAT
      (Receptor Selection and Amplification Technology) in which proliferative
      responses are monitored using a reporter gene. Individually, GTPase-deficient
      mutants (*) of G alpha q and G alpha 12, wild-type G alpha q, and m5 were active
      in R-SAT. G alpha 12* and m5 also induced focus formation. m2 was inactive in
      both assays. The ability of m5 to induce foci was significantly reduced by
      coexpression of G alpha q*. Synergistic effects of receptor/ G protein
      combinations were not observed in focus-forming assays but were readily detected
      by R-SAT. Coexpression of G alpha q with m5 induced constitutive activity in R
      SAT and increased the potency of agonists at m5 by 90-fold. G alpha q also evoked
      agonist-dependent responses from m2 but not constitutive activity. Agonist
      potency was increased 10-fold at m2 and decreased 15-fold at m5 when these
      receptors were coexpressed with G alpha qi5, a chimeric G protein containing the
      five C-terminal residues of G alpha i2, compared with coexpression with G alpha
      q. Both G alpha q and G alpha qi5 had biphasic effects on the proliferative
      responses to m5 and m2, respectively, inhibiting responses at high agonist
      concentrations. Coexpression of G alpha 12 or G alpha 12i5 had no effect on the
      concentration-response relationships of m5, but both elicited weak responses from
      m2. We conclude that although G alpha 12 is a more potent oncogene, G alpha q
      transduces m5-driven cellular responses. The demonstrations that proliferative
      responses can be elicited from a nonmitogenic receptor by altering the type and
      concentration of available G proteins and that constitutive responses can be
      induced by G proteins imply that both the magnitude and type of receptor
      initiated signal can be regulated at the level of G proteins in vivo.

PMID- 9003038
TI  - Identification of Ser-Pro and Thr-Pro phosphorylation sites in chicken
      neurofilament-M tail domain.
AB  - The tail domain of the midsize chicken neurofilament polypeptide (NF-M) contains
      several different types of Ser-Pro and Thr-Pro putative phosphorylation sites. We
      determined which of these sites are actually phosphorylated in vivo. Chick
      sensory neuron cultures were incubated in [32P]phosphate, and the cytoskeletal
      fraction was mixed with a neurofilament fraction prepared from adult chicken
      brain. NF-M was purified by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and digested with chymotrypsin, and two large fragments were
      isolated. These were individually cleaved with trypsin, endoprotease Lys-C, or
      endoprotease Glu-C, and peptides separated by two-dimensional high-voltage
      electrophoresis and thin-layer chromatography. 32P-labeled phosphopeptides were
      eluted from the cellulose plates and subjected to microsequencing and mass
      spectometry. We found that of 21 potential Ser-Pro and Thr-Pro phosphoacceptor
      sites, at least 20 are phosphorylated in vivo: all four Lys-Ser-Pro sites and at
      least 16 of the 17 Lys-Xaa-Xaa-Ser/Thr-Pro repeats. In addition, a novel Ser-Pro
      site in the extreme carboxy terminus is phosphorylated. This site, which has no
      proximal Lys residue, is also found in mammalian NF-M, but has not been reported
      to be phosphorylated. Together with three casein kinase I sites we have found
      recently in the acidic amino-terminal segment of the tail, a total of 24 or 25
      Ser and Thr phosphoacceptor sites have now been located in the chicken NF-M tail.

PMID- 9003039
TI  - L1/HNK-1 carbohydrate- and beta 1 integrin-dependent neural cell adhesion to
      laminin-1.
AB  - We have shown recently that mouse small cerebellar neurons adhere to a short
      amino acid sequence of the G2 domain of the laminin alpha 1 chain via the cell
      surface-expressed HNK-1 carbohydrate. Therefore, we were interested in
      identifying glycoproteins carrying the HNK-1 carbohydrate at the cell surface of
      these neurons. Adhesion of small cerebellar neurons to laminin is partially
      dependent on Ca2+, Mn2+, and Mg2+, indicating the involvement of integrins, which
      were identified as beta 1, alpha 3, and alpha 6. They could be shown to bind to
      laminin by a beta 1-dependent adhesion mechanism. None of these subunits was
      found to carry the HNK-1 carbohydrate. HNK-1-immunoreactive glycoproteins were
      immunoprecipitated and shown to consist of predominantly one molecular species,
      which was identified as the neural cell recognition molecule L1. L1 was
      demonstrated to bind in a concentration-dependent and saturating manner to
      laminin. The binding could be partially inhibited by Fab fragments of monoclonal
      antibodies against the HNK-1 carbohydrate and against the Ig-like domains of L1.
      Furthermore, antibodies to the Ig-like domains of L1 and beta 1 integrin
      inhibited partially cell adhesion to laminin. Determination of the association of
      L1, beta 1 integrin, and the HNK-1 carbohydrate on the cell surface of live
      cerebellar neurons by antibody-induced patching and copatching revealed HNK-1 to
      be linked to L1, but less so to beta 1 integrin. However, only negligible
      association was found between L1 and beta 1 integrin. Furthermore, it could be
      shown that adhesion to laminin is mediated by L1/HNK-1- and beta 1 integrin
      dependent mechanisms that act at least partially independent of each other.

PMID- 9003040
TI  - Synthesis and cytotoxic profile of a diphtheria toxin-neurotrophin-4 chimera.
AB  - A diphtheria toxin-neurotrophin-4/5 (NT-4/5) chimera (DAB389-NT4), in which the
      native receptor binding domain of diphtheria toxin was replaced with a synthetic
      gene encoding rat NT-4/5, was expressed, refolded, and purified. This fusion
      toxin has a deduced molecular mass of 60,163 and is formed by joining the first
      389 amino acids of diptheria toxin to amino acids 1-130 of mature rat NT-4/5,
      using an NH2-terminal bridge of 33 additional amino acids including six
      consecutive histidines. Neural cell types expressing only p75LNGFR or p75LNGFR
      and full-length or truncated TrkB were used to evaluate the cytotoxic efficacy of
      DAB389-NT4. The fusion toxin produced a concentration-dependent killing of all
      cell populations, with LC50 values that largely reflected the known NT-4/5
      binding affinities for these receptor proteins. Mean LC50 values ranged from
      2,960 pM in p75LNGFR-expressing neuro-2a neuroblastoma cells to 1,075 and 70 pM,
      respectively, in hippocampal astrocytes (p75LNGFR+/truncated TrkB+) and
      cerebellar granule cells (p75LNGFR+/TrkB+). The LC50 for DAB389-NT4 in receptor
      negative 3T3 fibroblasts was 20 nM. NT-4/5 and brain-derived neurotrophic factor
      but not ciliary neurotrophic factor added in excess neutralized DAB389-NT4
      cytotoxicity. NT-4/5, however, did not reduce the cytotoxicity of intact
      diphtheria toxin.

PMID- 9003041
TI  - Protein kinase C activators work in synergy with specific growth factors to
      initiate tyrosine hydroxylase expression in striatal neurons in culture.
AB  - Our previous studies indicate that, in the noncatecholamine (non-CA) neurons of
      the striatum, expression of the gene for the CA biosynthetic enzyme tyrosine
      hydroxylase (TH) can be initiated by the synergistic interaction of acidic
      fibroblast growth factor (aFGF) and a second partner molecule. In this study, we
      sought to determine whether the activators of protein kinase C (PKC) signaling
      pathways, either alone or in conjunction with various growth factors, is
      sufficient to induce TH in striatal neurons. We found that when the active beta
      from of 4 beta-12-O-tetradecanoylphorbol 13-acetate (TPA), but not the inactive
      alpha analogue, was incubated in the presence of aFGF, basic FGF, or brain
      derived neurotrophic factor, TH expression was initiated. Activation of the PKC
      pathways alone (in the absence of growth factors) did not mimic these effects,
      suggesting that multiple pathway activation is required for novel TH expression.
      Although other specific activators of PKC were effective growth factor partners,
      TPA was the most potent with an ED50 of 0.008 muM. Conversely, inhibitors of
      protein kinases, such as H7, H8, or H89, prevented the expression of TH by aFGF
      and TPA. Because pretreatment with protein (cycloheximide) or RNA synthesis
      (amanitin and actinomycin D) inhibitors eliminated the inductive effect of aFGF
      and TPA, we conclude that de novo transcription and translation are necessary for
      the expression of TH after convergence of both PKC and growth factor pathways.

PMID- 9003042
TI  - Expression of endothelin-converting enzyme in both neuroblastoma and glial cell
      lines and its localization in rat hippocampus.
AB  - Endothelin-converting enzyme is a phosphoramidon-sensitive metalloprotease that
      cleaves big endothelin to the potent vasoconstrictor peptide, endothelin. The
      converting enzyme is expressed in endothelial cells in a variety of tissues and
      in some secretory cells. In the present study, phosphoramidon-sensitive
      endothelin-converting enzyme activity has been demonstrated by radioimmunoassay
      in the neuroblastoma cell line, SH-SY5Y, and in Bu17 and C6 glioma lines. The
      identity of the activity was confirmed by immunoblotting, revealing a polypeptide
      of approximately 120 kDa in each of these lines, in D384 glioma cells, and in
      primary astrocytes. Immunofluorescence revealed the cell-surface location of
      endothelin-converting enzyme in the neuronal and glial cell lines and in primary
      astrocytes. Pretreatment of SH-SY5Y and Bu17 cells with phosphoramidon resulted
      in an apparent concentration of the enzyme protein in an intracellular
      compartment. Immunoperoxidase-staining of rat brain sections located this
      metalloprotease to the pyramidal cells of the hippocampus. Endothelin-converting
      enzyme-1 was revealed by in situ hybridisation in the neuronal and glial cell
      lines.

PMID- 9003043
TI  - Ethanol promotes apoptosis in cerebellar granule cells by inhibiting the trophic
      effect of NMDA.
AB  - When primary cultures of cerebellar granule neurons are grown in a physiological
      concentration of KCl (5 mM) they undergo apoptosis, which can be prevented by
      growing the cells in the presence of N-methyl-D-aspartate (NMDA). We now show
      that ethanol inhibits this trophic effect of NMDA, i.e., promotes apoptosis, and
      also inhibits the NMDA-induced increase in intracellular Ca2+ concentration in
      cells grown in 5 mM KCl. Both effects of ethanol show a similar concentration
      dependence and are reversed by a high concentration of glycine, the co-agonist at
      the NMDA receptor. The data suggest that the effect of ethanol on apoptosis is
      mediated, at least in part, by inhibition of NMDA receptor function. This effect
      of ethanol to increase apoptosis could contribute to the previously described in
      vivo sensitivity of the developing cerebellum to ethanol-induced damage.

PMID- 9003045
TI  - Nonmuscle myosin heavy chain B is recognized by a monoclonal antibody that
      inhibits GM1-enhanced neuritogenesis.
AB  - Addition of gangliosides to neuroblastoma cells maintained in vitro has been
      shown to enhance neuritogenesis. Although the mechanism by which they exert this
      effect is unknown, it has been postulated that they may act by adhering to cell
      surface proteins. In this article, we describe the isolation and identification
      of an S20Y murine neuroblastoma cell protein recognized by a monoclonal antibody
      that was prepared against putative GM1-binding proteins and shown to inhibit GM1
      enhanced neuritogenesis. The protein identified was nonmuscle myosin heavy chain
      B, which appears to function in neurite formation but may not adhere to
      gangliosides.

PMID- 9003044
TI  - The low-density lipoprotein receptor-related protein, a multifunctional
      apolipoprotein E receptor, modulates hippocampal neurite development.
AB  - The epsilon 4 allele of apolipoprotein E (apoE) is an important risk factor for
      Alzheimer's disease. A major neuronal receptor for apoE within the brain is the
      low-density lipoprotein receptor-related protein (LRP). Using primary cultured
      hippocampal neurons, we examined the role of LRP in early neuronal development.
      LRP, as well as a 39-kDa protein that regulates its activity, is localized
      abundantly in developing neurons. Both the 39-kDa protein and an anti-LRP
      antibody inhibited neurite outgrowth of primary hippocampal neurons cultured in
      either serum-containing medium or on cortical astrocyte monolayers in serum-free
      medium. It is noteworthy that microtubule-associated protein-2 immunoreactive
      process outgrowth was decreased significantly in hippocampal neurons cultured on
      cortical astrocytes derived from apoE-deficient mice and was not diminished
      further following incubation with LRP inhibitors. Thus, these results suggest
      that LRP can influence aspects of neuronal process development and that apoE
      containing lipoproteins may be one of the major LRP ligands that can contribute
      to this process.

PMID- 9003046
TI  - Residues specifically involved in down-regulation but not internalization of the
      m1 muscarinic acetylcholine receptor.
AB  - Human m1 muscarinic acetylcholine receptor mutants were screened to determine
      receptor domains and cellular pathways relevant to down-regulation. Mutations in
      the second intracellular loop and the junctions of the third intracellular loop
      of the receptor, where a role for receptor activation or internalization had been
      previously demonstrated in HEK293 cells, were selected for this study. To assess
      receptor down-regulation, the m1 receptor mutants were transfected into Chinese
      hamster ovary cells. Because receptor internalization is expected to precede down
      regulation, mutants displaying intact internalization were selected to permit
      interpretation of mutational effects on down-regulation alone. Four mutations
      were identified that specifically impaired down-regulation without altering
      receptor internalization: V127A, I211A, E360A, and K362A. The results define new
      receptor domains in the second intracellular loop and the junctions of the third
      intracellular loop that are involved in down-regulation. These same four mutants
      were also defective in signaling via the phospholipase C and the adenylyl cyclase
      pathways and in G protein activation, as measured by [35S]GTP gamma S binding.
      However, the level of second messenger stimulation correlated poorly with the
      extent of down-regulation. In summary, several mutations of the m1 receptor
      selectively affect down-regulation, demonstrating that internalization and down
      regulation represent distinct events driven by different cellular mechanisms.

PMID- 9003048
TI  - Amygdala kindling modifies extracellular opioid peptide content in rat
      hippocampus measured by microdialysis.
AB  - Opioid peptide release in the hippocampus was shown to be increased immediately
      following amygdala kindling stimulation in freely moving rats using microdialysis
      combined with a universal opioid peptide radioimmunoassay (RIA). Extracellular
      opioid peptide levels were elevated (55% above basal levels) within the first 10
      min after electrical stimulation-induced partial seizures in previously
      nonkindled animals. Fully kindled rats showed lower extracellular opioid peptide
      levels (40% reduction) during the interictal period [16 +/- 2.1 days (mean +/-
      SEM) after the last stage V seizure], in comparison with values obtained from the
      sham-kindled group under basal conditions. However, opioid peptide release in
      fully kindled rats increased above 152% of interictal levels within the first 20
      min after onset of fully kindled seizures, attaining peak levels equal to that of
      the partial kindled group and returning to prestimulation conditions 40-60 min
      following the ictal events. The majority of the immunoreactive material recovered
      from the hippocampus within the first 20 min following partial and generalized
      kindled seizures coeluted with dynorphin-A (1-6), dynorphin-A (1-8), and Leu
      enkephalin by HPLC/RIA analysis. It is proposed that the enhanced opioid peptide
      release in hippocampus induced by amygdala kindling stimulation might be
      associated with either enhanced excitability or seizure suppression as seizure
      susceptibility fluctuates. The reduced interictal opioid peptide levels may also
      underlie some interictal behavioral disturbances.

PMID- 9003047
TI  - Regulation of delta-opioid receptor mRNA levels by receptor-mediated and direct
      activation of the adenylyl cyclase-protein kinase A pathway.
AB  - The effects of activation of the adenylyl cyclase-protein kinase A pathway on the
      expression of delta-opioid receptor mRNA in the NG108-15 neuroblastoma x glioma
      cell line has been investigated. Activation of prostaglandin E1 (PGE1) receptors,
      which are positively coupled to adenylyl cyclase, resulted in a reduction in
      delta-receptor messenger RNA levels. Direct stimulation of adenylyl cyclase by
      forskolin or treatment of cells with the cyclic AMP analogue dibutyryl cyclic AMP
      (db-cAMP) mimicked the effect of PGE1. Down-regulation in receptor protein
      levels, as measured by loss of radioligand binding sites, was also observed and
      its extent correlated well with the decrease in the amount of delta-opioid
      receptor transcripts. D-Ser2-Leu-enkephalin-Thr6 (DSLET) inhibition of adenylyl
      cyclase activity was also diminished after db-cAMP treatment. Inhibitors of
      protein kinase A (PKA) partially reversed the PGE1- and db-cAMP-mediated
      repression of the delta-opioid receptor mRNA levels. The rate of degradation of
      delta-opioid receptor mRNA in the presence of actinomycin D was not altered in
      response to db-cAMP, suggesting that mRNA stability is not reduced by PKA action.
      The regulation of delta-opioid receptor mRNA levels by db-cAMP was not sensitive
      to the protein synthesis inhibitor cycloheximide, suggesting that de novo protein
      synthesis is not required in this process.

PMID- 9003049
TI  - Surface expression of the AMPA receptor subunits GluR1, GluR2, and GluR4 in
      stably transfected baby hamster kidney cells.
AB  - The surface expression of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA)-type glutamate receptor (GluR) subunits GluR1, GluR2, and GluR4 was
      studied in cultures of stably transfected baby hamster kidney (BHK)-570 cells.
      Two methods were used to quantify surface expression: cross-linking with the
      membrane-impermeant reagent bis (sulfosuccinimidyl) suberate (BS3) and labeling
      of surface receptors with the membrane-impermeant biotinylating reagent
      sulfosuccinimidyl 2-(biotinamido)ethyl-1,3-dithiopropionate (NHS-ss-biotin)
      followed by precipitation with neutravidin beads. Western blot analyses of
      control versus treated cultures revealed that, for all three GluR subunits
      examined, 25-40% of the total GluR population is located in the plasma membrane
      of the BHK-570 cells. This finding was corroborated by analyses of the surface
      expression of [3H]AMPA binding sites in the GluR-expressing BHK-570 cells
      performed via the biotinylation/precipitation method; these studies revealed that
      30-40% of the total binding site population is found in the plasma membrane.
      Analyses of combinations of the subunits, both GluR1 + GluR2 and GluR2 + GluR4,
      revealed that heteromeric combinations of the subunits are not trafficked to the
      surface more efficiently than homomeric receptors. For each of the three
      subunits, western blots revealed two distinct bands; removal of surface receptors
      reduced immunoreactivity for the upper band of each subunit by > 90%, whereas
      immunoreactivity for the lower band was reduced by only 10-20%. Treatment of
      extracts from the various cell lines with glycopeptidase F resulted in the
      collapse of the two bands into a single band of lower molecular weight,
      suggesting that the two original bands represent differentially glycosylated
      forms of the same polypeptides. These data indicate that the majority of the
      stably expressed GluR subunits in these cell lines are incompletely glycosylated
      and that complete glycosylation is associated with trafficking of the GluR
      subunits to the cell surface.

PMID- 9003050
TI  - Evidence that GABAA receptor subunit mRNA expression during development is
      regulated by GABAA receptor stimulation.
AB  - The expression of six mRNA species (alpha 2, alpha 3, alpha 5, beta 2, beta 3,
      and gamma 2) encoding for GABAA receptor subunits was followed in cultured early
      postnatal cortical neurons by in situ hybridization histochemistry. In untreated
      control cultures it was found that these subunit mRNA expression profiles closely
      follow those seen during development in vivo. alpha 3, alpha 5, and beta 3
      subunit expression declined, alpha 2 expression increased, whereas beta 2 and
      gamma 2 subunit mRNA expression remained relatively constant. To test the
      hypothesis that GABAA receptor stimulation regulates these expression profiles,
      we tested the effect of a GABAA receptor positive modulator, allopregnanolone,
      and a GABAA receptor noncompetitive antagonist, tert
      butylbicyclophosphorothionate (TBPS). It was found that allopregnanolone
      augmented the rate at which the alpha 3, alpha 5, or beta 3 subunit mRNA
      expression declined and prevented the increase in alpha 2 subunit mRNA
      expression. As well, allopregnanolone down-regulated beta 2 subunit mRNA
      expression. TBPS, on the other hand, up-regulated alpha 3, alpha 5, beta 2, and
      beta 3 subunit mRNA expression. It also down-regulated the expression of alpha 2
      subunit mRNA. Both allopregnanolone and TBPS had no effect on gamma 2 subunit
      mRNA expression. These results imply that the developmental switchover of GABA
      receptor subunit mRNA expression is regulated by GABAA receptor activity.

PMID- 9003051
TI  - Expression of the nicotinic receptor alpha 7 gene in tendon and periosteum during
      early development.
AB  - One of the most abundant nicotinic acetylcholine receptors expressed in the
      central and peripheral nervous systems is a species that contains the alpha 7
      gene product, binds alpha-bungarotoxin with high affinity, and has a high
      relative permeability to calcium. The alpha 7 gene is also expressed at low
      levels in embryonic muscle tissue. We show here that the alpha 7 gene is
      expressed in tendon fibroblasts and periosteal cells during development. In situ
      hybridizations identify alpha 7 transcripts in tissue sections containing
      embryonic tendon and periosteum. RNase protection experiments demonstrate alpha 7
      mRNA in primary tendon cells grown in culture. Immunofluorescence with subunit
      specific monoclonal antibodies reveals alpha 7 protein in embryonic tendon.
      Immunoprecipitation assays with the antibodies indicate that the alpha 7
      containing species in tendon is capable of binding alpha-bungarotoxin and that a
      similar species can be identified at low levels on the surface of fibroblasts in
      culture. The results show that the alpha 7 gene product is expressed in a range
      of tissues, including cells thought to be nonexcitable. The distribution of alpha
      7 expression early in development and the ability of alpha 7-containing receptors
      to elevate intracellular calcium suggest that the gene may influence a variety of
      calcium-dependent events during embryogenesis.

PMID- 9003052
TI  - Microtubules and microfilaments participate in the inhibition of synaptosomal
      noradrenaline release by tetanus toxin.
AB  - Tetanus toxin (TeTX) has been demonstrated to inhibit transmitter release by two
      mechanisms: Zn(2+)-dependent proteolytic cleavage of synaptobrevin and activation
      of a neuronal transglutaminase. Herein, attenuation of TeTX-induced blockade of
      noradrenaline release from synaptosomes was achieved by prior disassembly of
      microfilaments with cytochalasin D or breakdown of microtubules by colchicine or
      nocodazole. These drugs and monodansylcadaverine, a transglutaminase inhibitor,
      displayed some additivity in antagonizing the inhibitory effect of the toxin on
      synaptosomal transmitter release; as none of them reduced synaptobrevin cleavage,
      all appear to work independently of the toxin's proteolytic action. Prior
      stabilization of microtubules with taxol prevented the antagonism seen with
      colchicine, highlighting that this cytoskeletal component is the locus of the
      effect of colchicine. Replacement of Ca2+ with Ba2+ caused disappearance of the
      fraction of evoked secretion whose inhibition by TeTX is reliant on polymerized
      actin but did not alter the blockade by toxin that is dependent on microtubules.
      Two temporally distinguished phases of release were reduced by TeTX, and
      colchicine lessened its effects on both. Blockade of the fast phase (< or = 10 s)
      of secretion by TeTX was unaffected by cytochalasin D, but it clearly antagonized
      the toxin-induced inhibition of the slow (10-s to > or = 5-min) component; it is
      notable that such antagonism was accentuated during a second bout of evoked
      release. These findings are consistent with sustained release requiring
      dissociation of synaptic vesicles from the microfilaments, a step that seems to
      be perturbed by TeTX.

PMID- 9003053
TI  - Dopamine agonist-induced inhibition of neurotransmitter release from the awake
      squirrel monkey putamen as measured by microdialysis.
AB  - Male squirrel monkeys (Saimiri sciureus) were surgically prepared with cranial
      guide cannulae for acute microdialysis sampling of the putamen nucleus, a
      dopamine (DA)-rich brain region. On the day of an experiment an animal was placed
      in a Plexiglas restraining chair and a microdialysis probe was inserted through
      the guide into the putamen. Perfusates of artificial cerebrospinal fluid were
      collected every 20 min over several hours and analyzed via HPLC with
      electrochemical detection. DA D2/ D3 agonist drugs were administered either
      orally (p.o.) or subcutaneously (s.c.), and changes in levels of DA in the
      dialysates were measured. All of the drugs tested, i.e., quinpirole (0.5 mg/kg
      p.o.), talipexole (0.75 mg/kg p.o. or s.c.), and PD 135222 (7 mg/kg p.o.),
      decreased spontaneous DA overflow by approximately 40-50% during the first 2 h
      following dosing. In animals that routinely underwent the microdialysis procedure
      up to 23 times over a 2-year period, there was neither an appreciable change in
      basal DA overflow nor a significant change in the magnitude of drug response.
      These data suggest that DA D2/D3 agonists attenuate DA neuronal overflow in the
      primate brain, similar to effects seen in rodents. Furthermore, these results
      also demonstrate the utility of repeated intracerebral microdialysis as a tool to
      monitor dynamic changes in neurochemical activity in monkeys over a prolonged
      period of time.

PMID- 9003054
TI  - Norepinephrine microinjections in the hypothalamic paraventricular nucleus
      increase extracellular dopamine and decrease acetylcholine in the nucleus
      accumbens: relevance to feeding reinforcement.
AB  - Norepinephrine (NE) was microinjected into the paraventricular nucleus (PVN),
      while microdialysis was used to monitor extracellular dopamine (DA) and
      acetylcholine (ACh) in the nucleus accumbens (NAc). The PVN is a site where
      exogenously administered NE can act through alpha 2 receptors to elicit eating
      behavior and preference for carbohydrates. It was hypothesized that NE in the PVN
      acts on a behavior reinforcement system by altering the DA/ACh balance in the
      NAc. NE microinjections (80 nmol in 0.3 microliter), which effectively elicited
      feeding in satiated rats in a separate test, caused a significant increase in
      extracellular DA (109%) and decrease in ACh (-27%) when the same animals were
      tested in the absence of food. In contrast when the food was available and
      ingested, ACh increased (51%) instead of decreasing. These results support the
      hypothesis that a functional link exists between the PVN and the NAc in which DA
      helps initiate and ACh helps stop appetitive behavior involved in the
      reinforcement of eating.

PMID- 9003055
TI  - Transient elevation of interstitial N-acetylaspartate in reversible global brain
      ischemia.
AB  - We evaluated the changes of interstitial N-acetylaspartate (NAA) concentration
      ([NAA]e) in rat striatum by microdialysis following transient global ischemia and
      depolarization. The dialysate NAA concentration ([NAA]d) values were corrected
      for the in vivo recovery to obtain [NAA]e, by the use of [3H]mannitol in the
      perfusion fluid. During global ischemia the relative loss (RL) of [3H]mannitol
      decreased to 40% of preischemic values, reflecting the decrease in extracellular
      volume fraction. During reperfusion RL of [3H]mannitol quickly normalized. The
      [NAA]d doubled during transient ischemia, which, after correction for in vivo
      recovery, corresponds to a fivefold increase in [NAA]e (p < 0.05). Reperfusion
      induced a > 10-fold increase of [NAA]e (p < 0.01) with subsequent normalization
      after 45 min. KCl at 100 microM caused a reversible 50% reduction in RL of
      [3H]mannitol and a three times increase in [NAA]e (p < 0.05) but no further
      increase when normal perfusate was reintroduced. The mechanisms of NAA release
      from neurons are unknown but may involve the activation of unknown
      channels/carriers-possibly in relation to a volume regulatory response. The
      present study shows that the distribution of NAA in brain is dynamically
      regulated in acute ischemia and suggests that changes of NAA levels could be
      caused by other means than neuronal loss.

PMID- 9003057
TI  - Dopaminergic and serotonergic neurotransmission systems are differentially
      involved in auditory cortex learning: a long-term microdialysis study of
      metabolites.
AB  - Auditory cortex has been shown to be a site of widespread neuronal learning
      processes even in the context of simple auditory conditioning behavior. In view
      of their presumed role in determining behavioral and motivational relevance of
      incoming information we investigated whether the dopaminergic and serotonergic
      systems are involved in auditory cortex learning. Using a chronic brain
      microdialysis technique over 4 days, samples from auditory cortex were obtained
      before, during, and after daily footshock avoidance training simultaneously from
      trained gerbils and passive control animals or pseudotrained animals. Because of
      detection limits of dopamine and serotonin in auditory cortex, the response
      profiles of extracellular homovanillic acid as the metabolite of the dopaminergic
      system and of 5-hydroxyindoleacetic acid as the metabolite of the serotonergic
      system were determined from consecutive dialysis samples each day. The response
      of the dopaminergic system appeared to reflect the initial formation of the
      behaviorally relevant association exclusively during the first training day,
      whereas the serotonergic response appeared to correlate with the stress level of
      animals.

PMID- 9003056
TI  - Monoamine metabolism in the locus coeruleus measured concurrently with behavior
      during opiate withdrawal: an in vivo microdialysis study in freely moving rats.
AB  - Using microdialysis, changes in monoamine metabolism were monitored in the locus
      coeruleus of freely moving rats during opiate withdrawal concomitantly with
      behavioral symptoms. Rats were infused with morphine (2 mg/kg/h, s.c.) or saline
      for 5 days and challenged with naltrexone (100 mg/kg, s.c.) on day 6. Following
      naltrexone challenge, the classic behavioral symptoms of morphine withdrawal were
      observed in rats treated with morphine but not in saline-infused rats. In
      morphine-dependent rats, naltrexone induced a marked increase (280%) in dialysate
      concentrations of 3,4-dihydroxyphenylacetic acid, an index of the functional
      activity of the noradrenergic neurons in the locus coeruleus. The local
      concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were also
      increased (70%) during morphine withdrawal. Taken together, these results (a)
      confirm in unanesthetized rats the hypothesis of an activation by opiate
      withdrawal of noradrenergic neurons in the locus coeruleus and (b) suggest an
      increase in serotonergic transmission in the same nucleus during morphine
      withdrawal.

PMID- 9003058
TI  - Proteasome contributes to the alpha-secretase pathway of amyloid precursor
      protein in human cells.
AB  - A major histopathological hallmark in Alzheimer's disease consists of the
      extracellular deposition of the amyloid beta-peptide (A beta) that is
      proteolytically derived from the beta-amyloid precursor protein (beta APP). An
      alternative, nonamyloidogenic cleavage, elicited by a protease called alpha
      secretase, occurs inside the A beta sequence and gives rise to APP alpha, a major
      secreted C-terminal-truncated form of beta APP. Here, we demonstrate that human
      embryonic kidney 293 (HK293) cells contain a chymotryptic-like activity that can
      be ascribed to the proteasome and that selective inhibitors of this enzyme reduce
      the phorbol 12,13-dibutyrate-sensitive APP alpha secretion by these cells.
      Furthermore, we establish that a specific proteasome blocker, lactacystin, also
      induces increased secretion of A beta peptide in stably transfected HK293 cells
      overexpressing wild-type beta APP751. Altogether, this study represents the first
      identification of a proteolytic activity, namely, the proteasome, contributing
      likely through yet unknown intracellular relays, to the alpha-secretase pathway
      in human cells.

PMID- 9003060
TI  - Neuroprotection of lubeluzole is mediated through the signal transduction
      pathways of nitric oxide.
AB  - Neuronal survival after ischemic injury is determined through the induction of
      several biological pathways. We examined whether lubeluzole, an agent efficacious
      in both clinical and experimental models of cerebral ischemia, modulated the
      signal transduction mechanisms of nitric oxide (NO), a downstream mediator of
      anoxic neurodegeneration. Both pretreatment [NO survival = 23 +/- 3%,
      NO/lubeluzole (750 nM) survival = 63 +/- 2%, p < 0.001] and coadministration [NO
      survival = 25 +/- 3%, NO/lubeluzole (750 nM) survival = 59 +/- 3%, p < 0.001] of
      lubeluzole with NO generators equally protected cultured hippocampal neurons in a
      dose-dependent manner against the toxic effects of NO, suggesting that the agent
      protects by acutely modifying toxic cellular pathways rather than preconditioning
      the neuron before injury. The protection observed with lubeluzole was
      stereospecific but was not limited to pre- or coadministration. Lubeluzole also
      was found to significantly protect against the toxicity of NO for a period of 4-6
      h after NO exposure [NO survival = 31 +/- 2%, NO/lubeluzole (750 nM) survival at
      6 h = 56 +/- 3%, p < 0.001]. We conclude that the neuroprotective ability of
      lubeluzole is unique and involves the direct modulation of the NO pathway. In
      addition, the mechanisms of NO toxicity are dynamic and reversible processes
      that, if left unaltered, will lead to neuronal injury. Further investigation of
      the downstream signal transduction mechanisms below the level of NO generation
      may elucidate the specific cellular events responsible for neurodegeneration.

PMID- 9003059
TI  - Prostaglandin E2 induces interleukin-6 synthesis in human astrocytoma cells.
AB  - Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin
      6 (IL-6), have been implicated in the etiopathology of various inflammatory and
      degenerative disorders, including Alzheimer's disease (AD) and prion diseases.
      Nonsteroidal antiinflammatory drugs (NSAIDs), potent inhibitors of PG synthesis,
      appear to be beneficial in the treatment of AD. To assess whether PGs are able to
      induce IL-6 synthesis in cells of the CNS, IL-6 mRNA and protein syntheses were
      measured in a human astrocytoma cell line after stimulation with different PGs.
      PGE1 and PGE2, but not PGD2 and PGF2 alpha, led to a rapid and transient
      induction of IL-6 mRNA, followed by IL-6 protein synthesis. Furthermore, PGE2
      potentiated IL-1 beta-induced IL-6 mRNA synthesis. These results are discussed
      with respect to the participation of PGs in neurodegenerative diseases (and its
      inhibition by NSAIDs) by affecting cytokine expression.

PMID- 9003061
TI  - Prion protein fragment 106-126 differentially induces heme oxygenase-1 mRNA in
      cultured neurons and astroglial cells.
AB  - Heme oxygenase (HO), which catalyzes the degradation of heme, has two isozymes
      (HO-1 and HO-2). In brain the noninducible HO-2 isoform is predominant, whereas
      the inducible HO-1 is a marker of oxidative stress. Because brain oxidative
      stress might be present in prion-related encephalopathies (PREs), as in other
      neurodegenerative diseases, we investigated whether HO-1 mRNA was induced in
      neuronal and astroglial cell cultures by a peptide corresponding to residue 106
      126 of human prion protein (PrP). This peptide is amyloidogenic, and when added
      in vitro to cultured cells it reproduces the neuronal death and astroglial
      proliferation and hypertrophy occurring in PREs. HO-1 mRNA did not accumulate in
      rat cultured neurons from hippocampus or cortex exposed to PrP 106-126 (50 microM
      for 5 days). PrP 106-126 induced HO-1 mRNA accumulation in rat astroglial
      cultures depending on the exposure time and concentration, being maximal (33
      fold) after 7 days of exposure at 50 microM. The nonamyloidogenic amidated or
      amidated-acetylated PrP 106-126 was ineffective, as was a scrambled peptide used
      as control. N-Acetylcysteine reduced (50%) the accumulation of HO-1 mRNA in
      astroglial cells after PrP 106-126 (25 microM) given for 5 days. Thus, oxidative
      stress is apparently a feature of the toxicity of PrP 106-126, and it might also
      occur in PREs; induction of HO-1 could contribute to the greater resistance of
      astrocytes compared with neurons to PrP 106-126 toxicity.

PMID- 9003062
TI  - Characterization of the binding of amyloid-beta peptide to cell culture-derived
      native apolipoprotein E2, E3, and E4 isoforms and to isoforms from human plasma.
AB  - The epsilon 4 allele of apolipoprotein E (apoE, protein; APOE, gene) is a major
      risk factor for Alzheimer's disease (AD). Genetically, the frequency of the
      epsilon 4 allele is enriched in early-onset sporadic, late-onset familial, and
      common late-onset sporadic AD. ApoE is found in the extracellular amyloid-beta (A
      beta) deposits that are characteristic features of AD. In this study, we examined
      the interaction between A beta and apoE isoforms. The apoE isoforms used in this
      study were either produced by stably transfected Chinese hamster ovary cells
      (CHO) or were from human plasma. We report that when similar concentrations of
      the apoE isoforms were used, native nonpurified apoE3 from recombinant CHO
      derived sources bound A beta, but apoE4 did not. In fact, in our system, binding
      of recombinant apoE4 to A beta was never detectable, even after incubation for 4
      days. Furthermore, using the same assay conditions, native apoE2, like apoE3,
      binds A beta avidly. Furthermore, when human plasma apoE isoforms are tested in A
      beta binding experiments, apoE3 bound A beta more avidly than apoE4, and a major
      apoE/A beta complex (the 40-kDa form) was observed with plasma apoE3 but not
      apoE4. These data extend our understanding of apoE isoform-dependent binding of A
      beta by associating apoE2 with efficient apoE/A beta complex formation and
      demonstrate that native apoE3 (whether recombinant or derived from human plasma)
      forms sodium dodecyl sulfate-stable apoE/A beta complexes more readily than
      native apoE4. The different A beta-binding properties of native apoE4 versus
      native apoE3 provide insight into the molecular mechanisms by which the APOE
      epsilon 4 allele exerts its risk factor effects in AD.

PMID- 9003063
TI  - Production and secretion of adrenomedullin by cultured choroid plexus carcinoma
      cells.
AB  - Adrenomedullin is a potent vasodilator peptide that was originally isolated from
      pheochromocytoma. The production and secretion of adrenomedullin by cultured
      choroid plexus carcinoma cells were studied by radioimmunoassay and northern blot
      hybridization. Choroid plexus carcinoma is a rare malignant tumor derived from
      the epithelium of the choroid plexus. Immunoreactive adrenomedullin was detected
      in the conditioned medium of choroid plexus carcinoma cells (40.8 +/- 7.5
      fmol/10(5) cells/24 h; mean +/- SEM, n = 5). Reverse-phase HPLC of the
      conditioned medium showed one major peak of the immunoreactive peptide eluting in
      the position of synthetic human adrenomedullin and two smaller peaks eluting
      earlier. Addition of interleukin-1 beta (10 ng/ml) alone or in combination with
      three cytokines, interferon-gamma (100 U/ml), tumor necrosis factor-alpha (20
      ng/ml), and interleukin-1 beta (10 ng/ml), caused significant increases in the
      immunoreactive adrenomedullin concentrations in the medium (approximately 175 and
      293% of the control level, respectively). Northern blot analysis showed the
      expression of 1.6-kb adrenomedullin mRNA in the total RNA sample prepared from
      cultured choroid plexus carcinoma cells. Treatment with either interleukin-1 beta
      or the combination of three cytokines caused significant increases in levels of
      adrenomedullin mRNA in parallel with those in immunoreactive adrenomedullin
      concentrations in the conditioned medium. These findings raise a possibility that
      adrenomedullin is secreted from the choroid plexus and has physiological roles in
      the CNS via the CSF. In addition, adrenomedullin secreted from choroid plexus
      carcinoma may be related to the pathophysiology of the tumor.

PMID- 9003064
TI  - Neuroprotective effect of the iron chelator desferrioxamine against MPP+ toxicity
      on striatal dopaminergic terminals.
AB  - Microdialysis was used to evaluate the effect of desferrioxamine (DES) against 1
      methyl-4-phenylpyridinium (MPP+) toxicity. The presence of DES (40 fmol-40
      nmol/15 min for a total of 90 min) in the Ringer solution, coperfused with MPP+
      (40 nmol/15 min) on day 1, produced on day 2 a higher extracellular dopamine
      output after perfusion of MPP+ than in control MPP+ perfusion experiments, in
      which no DES was administered on day 1. Both Ringer perfusion alone (control
      Ringer) and coperfusion of 40 nmol DES with 40 nmol MPP+ on day 1 produced on day
      2 similar increases in extracellular dopamine output after a second MPP+
      perfusion. In the control Ringer experiment, note that the MPP+ on day 2 is the
      first MPP+ perfusion. Perfusion of 800 fmol FeCl3/15 min along with 40 nmol MPP+
      and 400 fmol DES on day 1 completely abolished on day 2 the neuroprotective
      effect found with 40 nmol MPP+ and 400 fmol DES; 800 fmol FeCl3 did not increase
      the neurotoxic effect of 40 nmol MPP+ perfusion. The ability of DES to protect
      against MPP+ toxicity may indicate a therapeutic strategy in the treatment of
      diseases when iron is implicated.

PMID- 9003065
TI  - Increased expression of cathepsins E and D in neurons of the aged rat brain and
      their colocalization with lipofuscin and carboxy-terminal fragments of Alzheimer
      amyloid precursor protein.
AB  - Age-related changes in the expression and localization of two distinct
      intracellular aspartic proteinases, cathepsin E (CE) and cathepsin D (CD), were
      investigated in the rat cerebral cortex and the brainstem by immunocytochemical
      and quantitative methods using discriminative antibodies specific for each
      enzyme. Nonlysosomal CE was barely detectable in these two brain tissues in the
      embryonic stages, whereas relatively high expression of lysosomal CD was observed
      in embryonic tissues. After birth, CE was increasingly expressed in these tissues
      with aging to attain maximal levels at 30 months of age. Western blot analyses
      revealed that CE existed predominantly as the mature enzyme at 2 and 17 months of
      age, whereas it was present as not only the mature enzyme but also the proenzyme
      at 30 months of age. On the other hand, CD was mainly present in the mature form
      throughout development, although its level in these tissues was also
      significantly increased with aging. The CE-positive cortical and brainstem
      neurons of the aged rat corresponded well with cells emitting autofluorescence
      for lipopigments. By the double-staining technique, most of the CE-positive
      cortical and brainstem neurons of the aged rat were also positive for antibody to
      the carboxyl-terminal fragments of amyloid precursor protein (APP634-695),
      intracellular accumulation of which is thought to be associated with age-related
      changes in the endosome/lysosome system. It is important that electron microscopy
      revealed that CE in brainstem neurons of the aged rat colocalized with CD in the
      lipofuscin-containing lysosomes. These results indicate that aging results in the
      increased expression and lysosomal localization of CE in cortical and brainstem
      neurons and changes in the endosomal/lysosomal proteolytic system, which may be
      related to lipofuscinogenesis and altered intracellular APP metabolism.

PMID- 9003066
TI  - Biochemical and temporal analysis of events associated with apoptosis induced by
      lowering the extracellular potassium concentration in mouse cerebellar granule
      neurons.
AB  - We analyzed biochemically and temporally the molecular events that occur in the
      programmed cell death of mouse cerebellar granule neurons deprived of high
      potassium levels. An hour after switching the neurons to a low extracellular K+
      concentration ([K+]o), a significant part of the genomic DNA was already cleaved
      to high-molecular-weight fragments. This phenomenon was intensified with the
      progression of the death process. Addition of cycloheximide to the neurons 4 h
      after high [K+]o deprivation resulted in no cell loss and complete recovery of
      the damaged DNA. DNA margination and nuclear fragmentation as assessed by 4,6
      diaminodiphenyl-2-phenylindole staining were observable in a few cells beginning
      approximately 4 h after the removal of high [K+]o and developed to nuclear
      condensation 4 h later. Six hours after high [K+]o deprivation, the DNA was
      fragmented into oligonucleosome-sized fragments. Within 6 h after removal of the
      extracellular K+, 50% of the neurons were committed to die and lost their ability
      to be rescued by readministration of 25 mM [K+]o. Similar to high [K+]o
      deprivation, inhibition of RNA or protein synthesis failed to halt neuronal
      degeneration of a similar percentage of cells 6 h after the onset of the death
      process. Mitochondrial function steadily decreased after [K+]o removal. An
      approximately 40% decrease in RNA and protein synthesis was detected by 6 h of
      [K+]o removal during the period of cell death commitment; rates continued to
      decline gradually thereafter. The temporal characteristics of the DNA damage and
      recovery, DNA cleavage to oligonucleosome-sized fragments, and the reduction in
      mitochondrial activity-events that occurred within the critical time-may indicate
      that these processes have an important part in the mechanism that committed the
      neurons to die.

PMID- 9003067
TI  - Effect of apolipoprotein E on neurite outgrowth and beta-amyloid-induced toxicity
      in developing rat primary hippocampal cultures.
AB  - The correlation between the epsilon 4 allele of apolipoprotein E (apoE) and
      Alzheimer's disease is well established. However, the role of apoE in normal as
      well as pathological brain processes remains unclear. We evaluated the effect of
      apoE treatment on development and beta-amyloid (A beta)-induced toxicity using
      primary cultures of developing rat hippocampal neurons. The source of apoE was
      conditioned media from HEK cells stably transfected with human apoE3 or apoE4
      cDNA, a preparation where apoE is lipid-associated. Morphological and biochemical
      changes in the cultures were assessed at 1 and 3 days following low- and high
      density plating with either apoE3 or E4 with or without A beta. Both apoE
      isoforms were neurotrophic, as measured by increased neurite length. Aged A
      beta(1-42), a peptide preparation exhibiting extensive fibril and aggregate
      formation, is toxic to these cultures. Addition of apoE3 and E4 significantly and
      comparably attenuated the A beta-induced reduction in both neurite length and
      cell viability. The level of protection against this toxicity was proportional to
      the neurotrophic actions of the two apoE isoforms. Thus, apoE acts as a potent
      growth factor in both the absence and the presence of A beta, supporting a
      potentially important role for apoE in neurobiology.

PMID- 9003068
TI  - Melatonin synthesis in the bovine pineal gland is regulated by type II cyclic AMP
      dependent protein kinase.
AB  - We investigated the expression of regulatory (R) and catalytic (C) subunits of
      cyclic AMP-dependent protein kinase (cAK; ATP:protein phosphotransferase; EC
      2.7.1.37) in the bovine pineal gland. In total RNA extracts of bovine pineal
      glands moderate levels of RI alpha/RII beta and high levels of C alpha and C beta
      mRNA were found. We were able to detect a strong signal for RII and C subunit at
      the protein level, whereas RI was apparently absent. Probing sections of the
      intact bovine pineal gland with RI and RII antibodies stained only RII in
      pinealocytes. Pairs of cyclic AMP analogues complementing each other in
      activation of type II cAK, but not cAKI-directed analogue pairs, showed
      synergistic stimulation of melatonin synthesis. Moreover, melatonin synthesis
      stimulated by the physiological activator norepinephrine in pineal cell cultures
      was inhibited by cAK antagonists. Taken together these results show the presence
      of RII regulatory and both C alpha and C beta catalytic subunits and thus cAKII
      holoenzyme in the bovine pineal gland. The almost complete inhibition of
      norepinephrine-mediated melatonin synthesis by the cAK antagonists emphasizes the
      dominant role of cyclic AMP as the second messenger and cAK as the transducer in
      bovine pineal signal transduction.

PMID- 9003069
TI  - Acetylcholine release in the rat prefrontal cortex in vivo: modulation by alpha 2
      adrenoceptor agonists and antagonists.
AB  - We have previously shown that the release of acetylcholine (ACh) in the medial
      prefrontal cortex of the conscious rat, as measured by microdialysis, is
      increased following intraperitoneal injection of the selective alpha 2
      adrenoceptor antagonist (+)-efaroxan. To characterize further the receptor
      pharmacology of this response, the effects of other selective alpha 2
      adrenoceptor ligands were examined. The alpha 2-adrenoceptor antagonists idazoxan
      (2.5 and 20 mg/kg), atipamezole (2.5 mg/kg), and fluparoxan (10 mg/kg) increased
      ACh outflow by up to 250-325% of basal levels over a 3-h period following
      intraperitoneal injection. The alpha 2-adrenoceptor agonists UK-14304 (2.5 mg/kg)
      and guanabenz (2.5 mg/kg) reduced ACh outflow by 80 and 60%, respectively.
      Clonidine (0.00063-0.16 mg/kg) had no significant depressant effect and at 2.5
      mg/kg increased ACh outflow to 233% of basal levels. These results indicate a
      modulatory role for alpha 2-adrenoceptors on the release of ACh in the rat
      prefrontal cortex in vivo. Based on the facilitatory effects produced by the
      antagonists alone, this alpha 2-adrenoceptor modulation appears to be tonic and
      inhibitory. The ability of alpha 2-adrenoceptor antagonists to enhance ACh
      outflow suggests a therapeutic usefulness in disorders where cortical ACh release
      deficits have been implicated.

PMID- 9003070
TI  - Stimulation of [3H] GABA and beta-[3H] alanine release from rat brain slices by
      cis-4-aminocrotonic acid.
AB  - cis-4-Aminocrotonic acid (CACA; 100 microM), an analogue of GABA in a folded
      conformation, stimulated the passive release of [3H] GABA from slices of rat
      cerebellum, cerebral cortex, retina, and spinal cord and of beta-[3H]alanine from
      slices of cerebellum and spinal cord without influencing potassium-evoked
      release. In contrast, CACA (100 microM) did not stimulate the passive release of
      [3H]taurine from slices of cerebellum and spinal cord or of D-[3H]aspartate from
      slices of cerebellum and did not influence potassium-evoked release of [3H]
      taurine from the cerebellum and spinal cord and D-[3H]-aspartate from the
      cerebellum. These results suggest that the effects of CACA on GABA and beta
      alanine release are due to CACA acting as a substrate for a beta-alanine
      sensitive GABA transport system, consistent with CACA inhibiting the uptake of
      beta-[3H]alanine into slices of rat cerebellum and cerebral cortex. The observed
      Ki for CACA against beta-[3H]alanine uptake in the cerebellum was 750 +/- 60
      microM. CACA appears to be 10-fold weaker as a substrate for the transporter
      system than as an agonist for the GABAc receptor. The effects of CACA on GABA and
      beta-alanine release provide indirect evidence for a GABA transporter in
      cerebellum, cerebral cortex, retina, and spinal cord that transports GABA, beta
      alanine, CACA, and nipecotic acid that has a similar pharmacological profile to
      that of the GABA transporter, GAT-3, cloned from rat CNS. The structural
      similarities of GABA, beta-alanine, CACA, and nipecotic acid are demonstrated by
      computer-aided molecular modeling, providing information on the possible
      conformations of these substances being transported by a common carrier protein.

PMID- 9003071
TI  - Evidence for circadian variations of thyroid hormone concentrations and type II
      5'-iodothyronine deiodinase activity in the rat central nervous system.
AB  - The 24-h patterns of tissue thyroid hormone concentrations and type II 5'- and
      type III 5-iodothyronine deiodinase (5'D-II and 5D-III, respectively) activities
      were determined at 4-h intervals in different brain regions of male euthyroid
      rats entrained to a regular 12-h light/12-h dark cycle (lights on at 6:00 a.m.).
      Activity of 5'D-II, which catalyzes the intracellular conversion of thyroxine
      (T4) to 3,3',5-triiodo-L-thyronine (T3) in the CNS, and the tissue concentrations
      of both T4 and T3 exhibited significant daily variations in all brain regions
      examined. Periodic regression analysis revealed significant circadian rhythms
      with amplitudes ranging from 9 to 23% (for T3) and from 15 to 40% (for T4 and 5'D
      II) of the daily mean value. 5'D-II activity showed a marked nocturnal increase
      (1.3-2.1-fold vs. daytime basal value), with a maximum at the end of the dark
      period and a minimum between noon and 4:00 p.m. 5D-III did not exhibit circadian
      patterns of variation in any of the brain tissues investigated. Our results
      disclose circadian rhythms of 5'D-II activity and thyroid hormone concentrations
      in discrete brain regions of rats entrained to a regular 12:12-h light-dark cycle
      and reveal that, in the rat CNS, T3 biosynthesis is activated during the dark
      phase of the photoperiod. For all parameters under investigation, the patterns of
      variation observed were in part regionally specific, indicating that different
      regulatory mechanisms may be involved in generating the observed rhythms.

PMID- 9003072
TI  - Epinephrine and norepinephrine act as potent agonists at the recombinant human
      dopamine D4 receptor.
AB  - The catecholamines dopamine (DA), epinephrine (EP), and norepinephrine (NE) play
      important roles in learning and memory, emotional states, and control of
      voluntary movement, as well as cardiovascular and kidney function. They activate
      distinct but overlapping neuronal pathways through five distinct DA receptors
      (D1R-D5R) and at least 10 different adrenergic receptors (alpha 1a/b/c, alpha
      2a/b/c-1/c-2, and beta 1/beta 2/beta 3). The D4R, which is localized to
      mesolimbic areas of the brain implicated in affective and emotional behavior, has
      a deduced amino acid sequence with homology to both adrenergic and dopaminergic
      receptor subtypes. We report here that DA, EP, and NE all show binding in the
      nanomolar range to three isoforms of the recombinant human D4R (hD4R): D4.2,
      D4.4, and D4.7. Submicromolar concentrations of DA, EP, and NE were sufficient to
      activate hD4R isoforms in two different functional assays: agonist-induced
      guanosine 5'-O-(3-[35S]thiotriphosphate) binding and modulation of adenylyl
      cyclase activity. DA was approximately fivefold more potent than EP and NE at the
      D4R, whereas activation of the human D2R required at least 100-fold higher
      catecholamine concentrations. Functional activation of the D4R by multiple
      neurotransmitters may provide a novel mechanism for integration of catecholamine
      signaling in the brain and periphery.

PMID- 9003073
TI  - Preparation and binding properties of radioiodinated analogues of dermorphin and
      deltorphin with high specificity for the mu- and delta-opioid receptors.
AB  - The synthesis, purification, chemical characterization, and binding properties of
      two 125I-labeled analogues of dermorphin and deltorphin-I are described. Native
      deltorphin-I and [Lys7] dermorphin sequences were elongated by an aminopentyl
      chain on their C-terminal amide function and alkylated with the 125I-labeled
      monoiodinated derivative of Bolton-Hunter reagent (BH*). The resulting
      radiolabeled peptides, epsilon-BH* [Lys7] dermorphin 5-aminopentylamide and omega
      BH* deltorphin-I 5-aminopentylamide, have kept most of the original properties of
      the parent peptides. They bind with high selectivity and specificity to the mu-
      (dermorphin analogue) or delta- (deltorphin-I analogue) opioid receptors from rat
      brain or from cells transfected with cDNAs encoding the mu and delta receptors.
      The autoradiographic distribution of specific binding sites for the 125I-labeled
      dermorphin and deltorphin-I analogues in rat brain is in complete agreement with
      previously reported localizations of mu- and delta-opioid receptors. The two
      radiolabeled peptides are the best ligands of mu- and delta-opioid receptors
      currently available in terms of sensitivity, specificity, and selectivity.

PMID- 9003074
TI  - Differential localization of the gamma 3 and gamma 12 subunits of G proteins in
      the mammalian brain.
AB  - The localization of two forms of the gamma subunit of G proteins, gamma 3 and
      gamma 12, was examined in the mammalian brain. Concentrations of these two gamma
      subunits increased markedly, as did those of glial fibrillary acidic protein,
      during postnatal development in the rat cerebral cortex. In aged human brains, by
      contrast, the concentration of gamma 3 tended to decrease with age, whereas that
      of gamma 12 in the temporal cortex increased slightly. An immunohistochemical
      study of human brains revealed that gamma 3 was abundant in the neuropil, whereas
      gamma 12 was localized in glial cells. In the hippocampal formation of aged human
      brains, levels of gamma 12-positive cells, as well as levels of glial fibrillary
      acidic protein- and vimentin-positive astrocytes, increased, in particular in the
      CA1 subfield and the prosubiculum, in which there was a decrease in the number of
      pyramidal cells. The appearance of gamma 12-positive cells associated with the
      loss of pyramidal cells was also observed in the hippocampus of rats that had
      been treated with kainic acid. These results indicate that gamma 12 is strongly
      expressed in reactive astrocytes. In a study of cultured neural cells, we found
      that gamma 12 was predominant in glioma cells, such as C6 and GA-1 cells, in
      contrast with the specific localization of gamma 3 in PC12 pheochromocytoma
      cells, which are neuron-like cells. Taken together, the results indicate that
      gamma 3 and gamma 12 are selectively expressed in neuronal and glial cells,
      respectively, and that concentrations of gamma 3 and gamma 12 in the brain are
      related to the numbers and/or extent of maturation of these cells.

PMID- 9003075
TI  - Posttranslational maturation of the prohormone convertase SPC3 in vitro.
AB  - The subtilisin-like prohormone convertase SPC3 is likely to play a role in the
      biosynthesis of a variety of biologically active peptides. SPC3 undergoes a
      series of posttranslational processing events during its biosynthesis. Multiple
      forms have been identified that show varying degrees of truncation at the
      carboxyl terminus. In this study we show that the 86-kDa form of recombinant SPC3
      with an intact carboxyl terminus can undergo rapid carboxyl-terminus truncation
      to produce a 64-kDa form. We have defined the optimal conditions for carboxyl
      terminus truncation in vitro. The carboxyl-terminus truncation reaction was less
      calcium sensitive, active over a broader pH range, and showed differences in
      inhibitor sensitivity compared with the enzymatic activities of full-length and
      truncated forms of SPC3 toward a fluorescent peptide substrate. Increases in
      enzymatic activity of 86-kDa SPC3 were also measured over a time frame consistent
      with conversion to the 64-kDa form. However, similar specific activities for both
      forms of the enzyme suggest such activity increases may not be due to carboxyl
      terminus truncation. The different enzymatic properties of the major molecular
      forms of SPC3 highlight the importance of understanding the molecular events
      regulating carboxyl-terminal processing of this endoprotease.

PMID- 9003076
TI  - Stably transfected human cells overexpressing rat brain endopeptidase 3.4.24.16:
      biochemical characterization of the activity and expression of soluble and
      membrane-associated counterparts.
AB  - We recently cloned endopeptidase-24.16 (neurolysin; EC 3.4.24.16), a neurotensin
      degrading peptidase likely involved in the physiological termination of the
      neurotensinergic signal in the central nervous system and in the gastrointestinal
      tract. We stably transfected human kidney cells with the pcDNA3-lambda 7aB1
      construction bearing the whole open reading frame encoding the rat brain
      peptidase. Transfectants displayed endopeptidase-24.16 immunoreactivity and
      exhibited QFS- and neurotensin-hydrolyzing activities, the biochemical and
      specificity properties of which fully matched those observed with the purified
      murine enzyme. Cryoprotection experiments and substrate degradation by intact
      plated cells indicated that transfectants exhibited a membrane-associated form of
      endopeptidase-24.16, the catalytic site of which clearly faced the extracellular
      domain. Transfected cells were unable to secrete the enzyme. Overall, our
      experiments indicate that we have obtained stably transfectant cells that
      overexpress an enzymatic activity displaying biochemical properties identical to
      those of purified endopeptidase-24.16. The membrane-associated counterpart and
      lack of secretion of the enzyme were clearly reminiscent of what was observed
      with pure cultured neurons, but not with astrocytes. Therefore, the transfected
      cell model described here could prove useful for establishing, by a mutagenesis
      approach, the structural elements responsible for the "neuronal" phenotype
      exhibited by the enzyme in transfected cells.

PMID- 9003077
TI  - Inhibition of bradykinin-induced calcium increase by phosphatase inhibitors in
      neuroblastoma x glioma hybrid NG108-15 cells.
AB  - Prior treatment of NG108-15 cells with phosphatase inhibitors including okadaic
      acid and calyculin A inhibited the elevation of cytosolic Ca2+ concentration
      ([Ca2+]i) induced by bradykinin by approximately 63%. This inhibition was
      dependent on the concentration of okadaic acid with an IC50 of 0.15 nM. Okadaic
      acid treatment only lowered the maximal response of [Ca2+]i increase and had no
      effect on the EC50 value for bradykinin regardless of the presence of
      extracellular Ca2+. Neither the capacity of 45Ca2+ accumulation within
      intracellular nonmitochondrial Ca2+ stores nor the magnitude of [Ca2+]i increase
      induced by thapsigargin was reduced by the treatment of okadaic acid. In
      contrast, the same phosphatase inhibitor treatment inhibited the bradykinin
      evoked inositol 1,4,5-trisphosphate (IP3) generation, the Mn2+ influx, and the
      capacity of mitochondrial Ca2+ accumulation. Furthermore, the sensitivity of IP3
      in the Ca2+ release was suppressed by okadaic acid pretreatment. Our results
      suggest that the reduction of bradykinin-induced [Ca2+]i rise by the promotion of
      protein phosphorylation was attributed to the reduced activity of phospholipase
      C, the decreased sensitivity to IP3, and the slowed rate of Ca2+ influx. Thus,
      phosphorylation plays a role in bradykinin-sensitive Ca2+ signaling cascade in
      NG108-15 cells.

PMID- 9003078
TI  - Localization and characterization of nitric oxide synthase in the rat
      suprachiasmatic nucleus: evidence for a nitrergic plexus in the biological clock.
AB  - Behavioral and electrophysiological evidence indicates that the biological clock
      in the hypothalamic suprachiasmatic nuclei (SCN) can be reset at night through
      release of glutamate from the retinohypothalamic tract and subsequent activation
      of nitric oxide synthase (NOS). However, previous studies using NADPH-diaphorase
      staining or immunocytochemistry to localize NOS found either no or only a few
      positive cells in the SCN. By monitoring conversion of L-[3H]arginine to L-[3H]
      citrulline, this study demonstrates that extracts of SCN tissue exhibit NOS
      specific activity comparable to that of rat cerebellum. The enzymatic reaction
      requires the presence of NADPH and is Ca2+/calmodulin-dependent. To distinguish
      the neuronal isoform (nNOS; type I) from the endothelial isoform (type III), the
      enzyme activity was assayed over a range of pH values. The optimal pH for the
      reaction was 6.7, a characteristic value for nNOS. No difference in nNOS levels
      was seen between SCN collected in day versus night, either by western blot or by
      enzyme activity measurement. Confocal microscopy revealed for the first time a
      dense plexus of cell processes stained for nNOS. These data demonstrate that
      neuronal fibers within the rat SCN express abundant nNOS and that the level of
      the enzyme does not vary temporally. The distribution and quantity of nNOS
      support a prominent regulatory role for this nitrergic component in the SCN.

PMID- 9003079
TI  - Distribution and subcellular localization of high-molecular-weight microtubule
      associated protein-2 expressing exon 8 in brain and spinal cord.
AB  - The expression of high-molecular-weight (HMW) microtubule-associated protein-2
      (MAP-2) expressing exon 8 (MAP-2 + 8) was examined by immunoblotting during rat
      brain development and in sections of human CNS. In rat brain, HMW MAP-2 + 8
      expression was detected at embryonic day 21 and increased during postnatal
      development. In adult rats, HMW MAP-2 + 8 comigrated with MAP-2a. In human adult
      brain, HMW MAP-2 + 8 was expressed in select neuronal populations, including
      pyramidal neurons of layers III and V of the neocortex and parahippocampal
      cortex, pyramidal neurons in the endplate, CA2 and subiculum of the hippocampus,
      and the medium-sized neurons of the basal ganglia. In the cerebellum, a
      subpopulation of Golgi neurons in the internal granular cell layer and most
      Purkinje cells were also stained. In the spinal cord staining was observed in
      large neurons of the anterior horn. Staining was present in cell bodies and
      dendrites but not in axons. At the ultrastructural level, HMW MAP-2 + 8
      immunoreactivity was observed on mitochondrial membranes and in postsynaptic
      densities (PSDs) of some asymmetric synapses in the midfrontal cortex and spinal
      cord. Immunoblots of proteins isolated from enriched mitochondrial and PSD
      fractions from adult human frontal lobe and rat brains confirmed the presence of
      HMW MAP-2 + 8. The presence of HMW MAP-2 + 8 in dendrites and in close proximity
      to PSDs supports a role in structural and functional attributes of select
      excitatory CNS synapses.

PMID- 9003080
TI  - Hypoxia dramatically increases the nonspecific transport of blood-borne proteins
      to the brain.
AB  - Increased cerebrovascular permeability is an important factor for the development
      of cerebral edema. To investigate the effect of hypoxia on the transport of blood
      borne proteins to the brain, we used a cell culture model of the blood-brain
      barrier (BBB) consisting of a coculture of brain capillary endothelial cells and
      astrocytes that closely mimics the in vivo situation. The permeability of
      albumin, a marker of the nonspecific transcellular route, is extremely low in
      this in vitro model of the BBB. After hypoxia, a huge increase in the
      permeability of albumin is detected. Despite the opening of the tight junctions
      already demonstrated after hypoxia, the increase in the permeability of albumin
      is mainly attributed to an increase of the non-specific vesicular transport in
      the cell, attested by the temperature dependence of the phenomenon and the
      visualization of labeled apotransferrin in the cytoplasm. The increase of this
      pathway could participate in the development of brain edema during hypoxia.

PMID- 9003081
TI  - Expression of sulfated gangliosides in the central nervous system.
AB  - Several sulfated lipids were detected in the ganglioside fraction isolated from a
      cell line of oligodendrocyte progenitors that had been metabolically labeled with
      [35S] sulfate. Separation of the ganglioside fraction by two-dimensional TLC
      showed that, except for galactosylceramide-sulfate, none of the sulfate-labeled
      lipids comigrated with those glycosphingolipids visualized by orcinol staining,
      indicating that these sulfolipids were quantitatively minor components. At least
      eight sulfate-labeled lipid bands were susceptible to desialylation by
      Arthrobacter ureafaciens neuraminidase, which resulted in the formation of three
      new bands that retained the labeled sulfate. Six of the sulfate-labeled lipid
      bands containing sialic acid were also susceptible to Vibrio cholerae
      neuraminidase, which generated two labeled bands that appeared identical to the
      two major products formed after treatment with A. ureafaciens neuraminidase. In
      vivo labeling of lipids from 14-day-old rat brain with [35S]-sulfate demonstrated
      that the synthesis of sulfated lipids containing sialic acid also occurred in
      intact brain tissue. These results show that sulfated gangliosides are
      synthesized in the CNS and that oligodendrocytes are one cell type that
      contributes to this synthesis.

PMID- 9003082
TI  - Glucosylceramide synthesis is required for basic fibroblast growth factor and
      laminin to stimulate axonal growth.
AB  - To test the hypothesis that neuronal growth requires the synthesis and supply of
      new membrane components to the growing neurite, we have examined the relationship
      between the synthesis of sphingolipids and the ability of two growth factors,
      basic fibroblast growth factor (bFGF) and laminin, to stimulate axonal growth in
      cultured hippocampal neurons. Both bFGF and laminin stimulate axonal growth by
      approximately fourfold; but the stimulatory effects of both factors can be
      abolished completely by two inhibitors of sphingolipid synthesis, fumonisin B1
      and D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol. By using these
      inhibitors, together with two stereoisomers of short acyl chain derivatives of
      ceramide, only one of which is metabolized to glucosylceramide, we demonstrate
      that ongoing synthesis of glucosylceramide, the simplest glycosphingolipid, is a
      prerequisite for both bFGF and laminin to stimulate axon growth. These data imply
      that the ability of a growth factor to stimulate neuronal growth is dependent on
      the synthesis of an essential membrane lipid.

PMID- 9003083
TI  - A wrong against humanity.

PMID- 9003084
TI  - Health registries. Ethics and security.

PMID- 9003086
TI  - DNA ploidy of ectopic pregnancy and first trimester spontaneous abortion
      investigated by flow cytometry.
AB  - BACKGROUND: To compare the success rate of DNA flow cytometry in determining the
      DNA ploidy status in ectopic pregnancy and first trimester spontaneous abortion.
      METHODS: Thirteen women with ectopic pregnancy (Group I) and 17 women with first
      trimester spontaneous abortion (Group II) were included into this study. DNA flow
      cytometric analysis was performed on all specimens. Aneuploidy was classified
      according to DNA index. The first trimester spontaneous abortions were also
      karyotyped after long-term culture of chronic villi. Student-t test and Fisher's
      exact test were used in statistical comparisons. RESULTS: DNA aneuploidy was
      found in five women with ectopic pregnancy (38.5%) versus in 12 women with first
      trimester spontaneous abortion (70.6%), and it was comparable. A triploidy and a
      tetraploidy were detected in group I. Six tubal ectopic pregnancies were
      unruptured at laparatomy and four of them had aneuploid DNA content. CONCLUSIONS:
      We believed that DNA flow cytometry was successful in determining the ploidy
      status of ectopic pregnancy and first trimester spontaneous abortion. In
      addition, it was interesting that ectopic pregnancies with aneuploid DNA content
      tended to be unruptured. However, this suggestion needs to be confirmed by
      further studies with larger numbers of cases.

PMID- 9003085
TI  - Serum from endometriosis patients impairs the development of mouse embryos in
      vitro--comparison with serum from tubal obstruction patient and plasmanate.
AB  - BACKGROUND: The aim of this study was to evaluate the inhibitory effect of serum
      from endometriosis. To determine the effects of serum obtained from patients with
      endometriosis on mouse embryo development, we compared the fertilization and
      cleavage rates of mouse embryo in a standard mouse embryo culture system.
      METHODS: Sera were collected from 13 individuals who were diagnosed endometriosis
      and ten individuals who were diagnosed as having tubal obstruction. Mouse embryos
      were fertilized and cultured in vitro with serum supplement obtained from
      patients with endometriosis (n = 13) and tubal obstruction (n = 10), and
      plasmanate (n = 10). RESULTS: The fertilization rate was 26.6 +/- 14.9% in
      patients serum with endometriosis, and the cleavage rate was 21.2 +/- 9.1%,
      respectively. However, the fertilization rates were 60.9 +/- 12.5% (tubal
      obstruction group), and 77.3 +/- 14.7% (plasmanate group), the cleavage rates
      were 32.2 +/- 16.4% and 36.2 +/- 9.9%, respectively. CONCLUSIONS: Serum from
      patients with endometriosis revealed toxic effects on mouse embryos in vitro. The
      use of plasmanate instead of whole serum from patients with endometriosis will
      hopefully bring a better understanding of embryo development.

PMID- 9003087
TI  - Inhibition of contractile responses of human myometrium and intramyometrial
      arteries by potassium channel openers.
AB  - OBJECTIVES: The effects of cromakalim and pinacidil on the contractile activity
      of the isolated human myometrium and intramyometrial arteries were studied.
      MATERIAL AND METHOD: Myometrial strips and pieces of uterine arteries were
      obtained from women undergoing hysterectomy. Contractions were recorded under
      isometric conditions. RESULTS: Both compounds (10(-9) M-5 x 10(-6) M) inhibited
      the spontaneous activity of the myometrium and vasopressin induced contractions
      of myometrium and intramyometrial arteries. There was no statistically
      significant difference in the responses of both tissues to cromakalim or
      pinacidil. Both compounds reduced responses of myometrium and intramyometrial
      arteries to low concentration of K+ (< 40 mM) but did not decrease contractions
      induced by 40 mM and 80 mM. CONCLUSION: The combined effect on the uterus and
      intrauterine vasculature would suggest a potential in the use of cromakalim or
      pinacidil for the treatment of dysmenorrhea.

PMID- 9003088
TI  - Immunohistochemical assessment of steroid hormone receptors in tissues of the
      anal canal. Implications for anal incontinence?
AB  - BACKGROUND: A prerequisite for a hormonal influence on anal continence in women
      is the presence of hormone receptors in the tissues of the anal canal. Using
      immunohistochemical techniques, we demonstrated and localized estrogen and
      progesterone receptors (ER, PR) in tissue sections of the anal canal. METHODS:
      Thirty-five specimens of the anorectal region from 21 patients (14 women, seven
      men) were examined histologically for smooth muscle (present in specimens from
      ten females and in seven males), striated muscle (present in three females and
      five males), and perimuscular connective tissue (present in 12 females and seven
      males). Immunostaining for ER and PR was then performed by incubating with
      primary anti-ER and anti-PR antibody and visualization of specific antibody
      binding by the ABC technique with DAB as chromogen. RESULTS: Positive staining
      for ER and PR was seen exclusively over cell nuclei. Estrogen receptors were
      found in the smooth muscle cells of the internal sphincter of all females (10/10)
      and in four of the seven males. Staining for ER was detected in the perimuscular
      connective tissue of all females (12/12) and in four of the seven males. No
      specific staining for ER or PR was found in the nuclei of striated muscle cells
      of the external sphincter in males or females (n = 8). In females, about 50% of
      the ER-positive tissues were also found to be positive for PR. Amongst the male
      patients, only one exhibited staining for PR, and this was confined to the smooth
      muscle. CONCLUSIONS: Expression of ER is a constitutional feature of the
      connective tissue and smooth muscle cells of the anal continence organ. Estrogen
      receptors and PR are not detectable in the striated muscle fibers of the external
      anal sphincter in either sex. The presence of ER in the stroma and smooth muscles
      of the anal canal suggests that these tissues are targets for estrogen. This
      constitutes a theoretical basis for the beneficial effects of estrogen and
      progestin replacement on anal continence in postmenopausal women.

PMID- 9003089
TI  - Variation in lipid levels during pregnancy in women with different types of
      hypertension.
AB  - OBJECTIVES: To evaluate the levels of serum lipids (cholesterol and
      triglycerides) in pregnant women with different types of hypertension, at the
      first, second and third trimesters of pregnancy. METHODS: Cholesterol and
      triglyceride levels at the first, second and third trimesters of gestation were
      recorded for 115 women with hypertension during pregnancy, and 115 healthy
      pregnant women matched for age and body mass index. Cases were classified as
      having mild gestational hypertension (25), severe gestational hypertension (15),
      mild preeclampsia (20), severe preeclampsia (20), chronic hypertension (20), and
      superimposed preeclampsia (15). RESULTS: Cholesterol levels were not
      statistically different between cases and controls in any form of hypertension.
      At 20 and 34 weeks' gestation, triglyceride levels were significantly higher than
      controls in women with severe gestational hypertension, mild and severe
      preeclampsia, and superimposed preeclampsia, but not in mild gestational
      hypertension or chronic hypertension. The significant elevation in triglycerides
      was already present at 10 weeks in mild and severe preeclampsia. CONCLUSIONS: The
      data suggest that the alterations in lipid metabolism observed in preeclampsia
      are already present at the first trimester of pregnancy. Women with severe
      gestational hypertension presented a pattern of triglycerides similar to that of
      preeclamptic women, but mild gestational hypertension resembled chronic
      hypertension in this respect. This supports the concept that, although in many
      cases gestational hypertension represents latent essential hypertension, some of
      these women, probably the most severe cases, present with true pregnancy-induced
      hypertension, or nonproteinuric preeclampsia.

PMID- 9003090
TI  - Fetal exposure to tobacco smoke products: a comparison between self-reported
      maternal smoking and concentrations of cotinine and thiocyanate in cord serum.
AB  - BACKGROUND: The objective of the study was to assess the relationship between
      maternal smoking habits and biomarkers of tobacco smoke measured in cord serum.
      METHODS: The study population comprised 202 mothers, 42 daily smokers, 24
      occasional smokers and 136 nonsmokers. Information on maternal smoking habits was
      collected in a self-administered questionnaire at birth and compared with
      cotinine and thiocyanate concentrations in cord serum. RESULTS: In linear
      regression analysis, a unit increase in daily cigarette smoking corresponded to a
      4.4 ng/ml (95% CI: 1.1-7.6) increase in cotinine concentration and 2.3
      mumol/l(0.8-3.8) in thiocyanate. A cut-off point of 14 ng/ml cotinine separated
      well between daily smokers (88% above) and nonsmokers (96% below), but revealed a
      classification problem in occasional smokers (46% above). CONCLUSION: Cord serum
      cotinine and thiocyanate concentrations are related to daily smoking rate during
      pregnancy, but these concentrations vary considerably among occasional smokers.
      Detailed information on smoking habits is the key issue in understanding the
      adverse fetal effects of occasional smoking during pregnancy.

PMID- 9003092
TI  - Breech infants: vaginal or cesarean delivery?
AB  - BACKGROUND: This study was undertaken to determine whether planned vaginal or
      elective cesarean delivery is better for singleton term breech infants and their
      mothers. METHODS: We studied deliveries of 388 singleton term breech infants that
      were born in our teaching hospital in Vienna. We follow well defined criteria for
      vaginal delivery versus cesarean section of term breech fetuses. We thus compared
      280 (72%) cases scheduled for vaginal delivery with 108 (28%) scheduled cesarean
      sections with regard to neonatal mortality and morbidity, including Apgar score,
      umbilical artery pH, and postpartum maternal morbidity. RESULTS: Vaginally
      delivered fetuses of primiparas had lower five-minute Apgar scores (5% < Apgar 7)
      and a lower umbilical artery pH (39% below 7.2). This is significantly different
      from the abdominally delivered primiparas (no Apgar below 7, only 11% with an
      artery pH below 7.2). Multiparas did not show significantly different results
      with regard to Apgar scores and umbilical artery pH between the different modes
      of delivery. Postpartum maternal morbidity was not different between the two
      groups. CONCLUSION: The results suggest that planned vaginal delivery of
      singleton breech infants of primiparas result in newborns with lower Apgar
      scores, a lower umbilical artery pH and a poorer fetal outcome. On the other
      hand, it seems that singleton term infants of multiparas do not profit from
      cesarean delivery.

PMID- 9003093
TI  - The number of follicles and ovarian volume in the assessment of response to
      clomiphene citrate treatment in polycystic ovarian syndrome.
AB  - OBJECTIVE: To evaluate whether the number of follicles and ovarian volume have
      any significance in evaluating the response to clomiphene citrate treatment in
      polycystic ovarian syndrome (PCOS). DESIGN: A prospective study of 70 infertile
      women, 44 of which were diagnosed with polycystic ovarian syndrome. MAIN OUTCOME
      MEASURES: Follicle numbers and volumes in both ovaries, hormonal profile,
      response to Clomiphene Citrate(CC). RESULTS: Ovarian volume was significantly
      greater in cases with polycystic ovarian syndrome than controls. However, ovarian
      volume in the Clomiphene Citrate nonresponders was significantly greater than in
      Clomiphene Citrate responders in the polycystic ovarian syndrome group. The
      number of small follicles was significantly higher in cases with polycystic
      ovarian syndrome than controls, and in the Clomiphene Citrate nonresponder group
      this number was also significantly higher than in Clomiphene Citrate responders.
      Endocrine features of patients with polycystic ovarian syndrome revealed that
      Dehydroepiandrostenedione sulfate, Androstenedione, follicle stimulating and
      luteinizing hormone do not discriminate between patients who respond to
      Clomiphene Citrate and those who do not respond. However, Testosterone and
      luteinizing hormone levels differ significantly in responders and nonresponders.
      CONCLUSIONS: Small multiple follicles (> 9) and enlarged ovarian volume (> 6.8
      ml) were the most prominent transvaginal ultrasonographic features of ovaries in
      Clomiphene Citrate nonresponsive patients with polycystic ovarian syndrome.
      Higher levels of Testosterone, luteinizing hormone and significantly higher
      number of small follicles were associated with lack of Clomiphene Citrate
      response. These ultrasonographic features and laboratory assays could be
      clinically useful for distinguishing better the Clomiphene Citrate nonresponders
      from responders.

PMID- 9003091
TI  - Induced abortions and childbirths: trends in Estonia, Latvia, Lithuania, Russia,
      Belarussia and the Ukraine during 1970 to 1994.
AB  - BACKGROUND: To analyse trends in childbirth, induced abortions and maternal
      morbidity from 1970 to 1994 in Estonia, Latvia, Lithuania, Russia, Belarussia and
      the Ukraine. METHODS: Official health statistics from the six countries were
      compiled and analysed. RESULTS: High abortion rates (up to 142 per 1000 women of
      fertile ages and years) were seen in all countries analysed, but since 1980 a
      continuing decrease is noted for Estonia, Latvia and Kalimingrad with a lowest
      rate of 50 abortions/1000 women/year in Latvia in 1994. Teenage abortions and
      childbirths are increasing. Maternal mortality, including complications of
      abortions, is still a reality in all the countries studied. CONCLUSION: The high
      abortion frequencies in all countries studied here indicate that national
      abortion prevention programs are needed. Such programs should focus on education,
      both of medical professionals, teenagers, fertile women and males. Concomitantly,
      the availability of cheap and modern contraceptives must increase, especially to
      defined risk groups.

PMID- 9003094
TI  - Recurrent first trimester spontaneous abortion associated with antiphospholipid
      antibodies: a pilot study of treatment with intravenous immunoglobulin.
AB  - BACKGROUND: Antiphospholipid antibodies, unassociated with an underlying
      connective tissue disease, have repeatedly been detected in women suffering from
      recurrent spontaneous abortions. Several therapeutic regimens have been advocated
      for pregnant women with recurrent fetal loss and antiphospholipid antibodies.
      However, most of these approaches were empirical, using several drugs
      simultaneously, and most reports describe single cases or limited series.
      PATIENTS AND INTERVENTIONS: In a pilot study, thirty-eight women with a history
      of three or more consecutive first trimester spontaneous abortions and
      antiphospholipid antibodies were treated with intravenous immunoglobulin. As soon
      as pregnancy had been confirmed, intravenous immunoglobulin was administered at a
      dose of 300 mg/kg bodyweight, and infusions were repeated at three-weekly
      intervals until the 16th-17th week of pregnancy. RESULTS: Pregnancy proceeded
      beyond the first trimester in 34 of the patients (89.4%), and 31 patients (81.4%)
      gave birth to healthy infants at 37 to 42 weeks' gestation. CONCLUSIONS: Although
      the results are promising, randomized placebo-controlled trials are necessary to
      exclude the influence of other factors (e.g. intense obstetric supervision and
      psychological factors) on pregnancy outcome and confirm the effectiveness of
      intravenous immunoglobulin in patients with recurrent spontaneous abortions and
      antiphospholipid antibodies.

PMID- 9003095
TI  - Serum endometrial IgG antibodies and soluble CD23 concentrations in patients with
      endometriosis.
AB  - OBJECTIVE: Serum endometrial antibodies have been found inconsistently in
      patients with endometriosis. Soluble CD23 is elevated in diseases associated with
      B cell activation. We evaluated serum levels of soluble CD23 and endometrial IgG
      antibodies in patients with endometriosis to determine whether there is B cell
      activation in this condition. DESIGN: Fifty-seven patients with pelvic pain
      diagnosed as endometriosis and 40 patients without pelvic pain or endometriosis
      who had laparoscopic sterilisation were sequentially recruited into the study.
      Blood was collected and the sera assayed by ELISA for endometrial IgG antibodies
      and soluble CD23. RESULTS: There was a significant difference between
      endometriosis and control group in both the serum IgG endometrial antibodies (p <
      0.05) and soluble CD23 (p < 0.05). There was significant but weak correlation
      between endometrial antibodies and soluble CD23 (r = 0.3, p = 0.039),
      particularly in mild but not severe endometriosis. CONCLUSIONS: These data
      suggest the existence of B cell activation in patients with endometriosis with a
      significant correlation between endometrial antibodies and soluble CD23. Mild
      endometriosis appears to be immunologically more active than the severe form. The
      value of soluble CD23 in the management of endometriosis needs further
      evaluation.

PMID- 9003097
TI  - Validity of a scored urological history in detecting detrusor instability in
      female urinary incontinence.
AB  - BACKGROUND: Kauppila and co-workers published in 1982 a detrusor instability
      score (DIS) for women with urinary incontinence. The aim of this study was to
      determine the validity of the DIS in an outpatient clinic for urogynecology.
      METHODS: The DIS questionnaire was incorporated as part of an independent history
      at the first consultation. The DIS was compared with clinical diagnosis in 250
      patients consecutively referred for evaluation. Sensitivity, specificity.
      positive predictive value (PPV), negative predictive value (NPV) and overall
      accuracy of the DIS in diagnosing genuine stress incontinence (GSI) were
      calculated using the gynecologist's clinical diagnosis based on urodynamic
      findings as the gold standard. An ROC-curve was constructed for determining the
      optimum cut-off point for the DIS for women with GSI. RESULTS: A cut-off point at
      7 for the DIS, yielded sensitivity = 0.77, specificity = 0.52, PPV = 0.74, NPV =
      0.52 and an overall accuracy = 0.68. Optimum cut-off point for GSI according to
      the ROC-curve was at a DIS-value of 5, yielding sensitivity = 0.60, specificity =
      0.77, PPV = 0.82, NPV = 0.52 and overall accuracy = 0.66. CONCLUSIONS: A cut-off
      point at 7 diagnosed 159 women (64%) as having GSI, 41 of them (16% of 250)
      having a false positive DIS. Similarly, a cut-off point at 5 diagnosed 112 women
      (45%) as having GSI, 20 of them (8% of 250) having a false positive DIS. These
      women, if otherwise feasible and indicated, might perhaps undergo continence
      surgery without preoperative urodynamics. A lower cut-off point than originally
      proposed ought therefore to be used if the DIS is to become a useful preoperative
      tool for this kind of surgery.

PMID- 9003096
TI  - Contraceptive practice and attitudes in Sweden 1994.
AB  - OBJECTIVE: To investigate current contraceptive practice in Sweden and Swedish
      women's attitudes towards various contraceptive methods. METHODS: In 1994, a
      random sample of Swedish women (n = 2330), aged 15-45 years (stratified according
      to age and geographic distribution), were invited by telephone to participate in
      the study. Women (n = 1788) who accepted the invitation to participate were sent
      a postal questionnaire. RESULTS: Completed questionnaires were returned by 1422
      women (overall response rate: 61.0%). The sample was somewhat skewed towards
      higher educational level, but in other demographic respects no great deviations
      from the parent population were observed. The distribution of contraceptive
      methods in fertile, sexually active women who wished to avoid pregnancy was as
      follows: oral contraceptives (OCs) 33%, OC plus barrier method 5%, intrauterine
      device 21%, barrier methods 23%, sterilization 5% (female 3%; male 2%) and
      injectable steroids 2%. The overall pattern of contraceptive use in women aged 15
      45 years had changed very little compared to results of a similar survey
      performed in 1987. However, the use of less effective methods (periodic
      abstinence, coitus interruptus and no method grouped together) was considerably
      lower among teenagers in 1994 (3%) than in 1987 (18%). The use of these
      traditional methods was still high in women aged over 35 years (15-17%). A large
      number of women considered medical methods of contraception to be reliable and
      easy to use but many were concerned about the safety for health of medical
      methods. CONCLUSIONS: Contraceptive practice changed towards more frequent use of
      medical, effective methods among young Swedish women, but not in the total female
      population. The latter was among others related to the relatively high use rates
      of less effective methods among women aged over 35. Women were concerned about
      the health safety of medical methods and relatively low percentages of women
      reported having received advice from health care professionals to use effective
      methods.

PMID- 9003098
TI  - Paget's disease of the vulva: report of five cases.

PMID- 9003099
TI  - Bilateral pyogenic sacroiliitis following uncomplicated pregnancy and labor.

PMID- 9003101
TI  - Negotiating effectively in academic medicine.

PMID- 9003100
TI  - Sexually transmitted diseases in Swedish women with experience of casual sex with
      men of foreign nationalities within Sweden.

PMID- 9003102
TI  - Hughes syndrome: perspectives on thrombosis and antiphospholipid antibody.

PMID- 9003103
TI  - The prevalence and clinical associations of anticardiolipin antibodies in a large
      inception cohort of patients with connective tissue diseases.
AB  - PURPOSE: To determine the prevalence and clinical associations of anticardiolipin
      antibodies (aCL) in a blinded, controlled study of patients with a variety of
      connective tissue diseases (CTD) using a standardized aCL testing system.
      PATIENTS AND METHODS: Anticardiolipin antibodies (IgG, IgM, and IgA) were
      measured by direct enzyme-linked immunosorbent assay (ELISA) in the baseline
      serum samples of patients enrolled in a Cooperative Study of Systematic Rheumatic
      Diseases (CSSRD), National Institutes of Health (NIH) supported, 5-year inception
      cohort, prospective study of early rheumatic diseases: rheumatoid arthritis (RA,
      n = 70), systemic lupus erythematosus (SLE, n = 70), scleroderma (PSS, n = 45),
      myositis (PM/DM, n = 36), and early undifferentiated connective tissue disease
      (EUCTD, n = 165). Diagnosis was based on standardized criteria and determined at
      the last study visit. A nested group of patients with Sjogren's syndrome (SJ, n =
      44) was also defined. Serum from 200 blood donors (BB) served as controls.
      Additional patients with known antiphospholipid syndrome (APS, n = 33) and ANCA
      related renal vasculitis (ANCA, n = 52) were also studied. Laboratory personnel
      were blinded to sample diagnostic group. RESULTS: The prevalence of either IgG or
      IgM aCL among each diagnostic group was RA 15.7%, SLE 15.76%, PSS 6.7%, PM/DM
      8.3%, EUCTD 9.1%, SJ 6.8%, ANCA 3.8%, and BB controls 4.0%. Prevalence of aCL was
      significantly different for both the RA and SLE groups versus BB controls (P <
      0.01) but not among other diagnostic groups. Only 2 study patients had positive
      tests for IgA aCL (1 with PM/DM and 1 with EUCTD) versus 15% of APS with positive
      IgA aCL. Study patients positive for IgG or IgM aCL were significantly more
      likely to have hemolytic anemia or a positive serologic test for syphilis and
      less likely to have Raynaud's phenomenon. However, no associations were found
      between aCL positivity and thrombocytopenia, seizures, renal insufficiency,
      presence of a positive antinuclear antibody or rheumatoid factor, subcutaneous
      nodules or digital ulcers. CONCLUSIONS: Based on results from this large CSSRD
      inception cohort, anticardiolipin antibodies are present in approximately 16% of
      patients with RA or SLE but are less common in patients with PSS, PM/DM, EUCTD,
      SJ, and ANCA vasculitis, where their prevalence approaches that in the normal
      population. Few consistent clinical association can be found among patients with
      CTD who are aCL positive. The complete diagnostic and prognostic importance and
      specificity of these antibodies remains to be fully determined.

PMID- 9003104
TI  - Utilization of echocardiography by internists and cardiologists: a comparative
      study.
AB  - OBJECTIVE: To compare the utilization of echocardiography as a diagnostic tool by
      internists and cardiologists. DESIGN: Retrospective study. SETTING: Tertiary care
      university hospital. METHODS: Indications and clinical utility of
      echocardiographic studies ordered by cardiologists (group A, n = 301) and
      internists (group B, n = 297) were compared by chart review. The two groups of
      patients were analyzed to determine if the studies detected new cardiac pathology
      and/or altered patient management. RESULTS: The proportion of studies with
      abnormal results were similar in both groups (19% versus 14%, P > 0.05). The
      results of echocardiography, however, led to a change in management more often
      when the study was ordered by cardiologists (16% versus 10%, P < 0.05). A
      significantly greater proportion of studies were ordered for evaluation of
      valvular function by internists (44% versus 33%, P < 0.05). Echocardiography
      detected valvular abnormalities in a similar proportion of cases in groups A and
      B (14% versus 10%, P > 0.05). However, diagnostic yield was very poor when the
      study was performed in patients with suspected mitral valve prolapse in both
      groups. Cardiologists utilized echocardiography more often for evaluation of left
      ventricular function (35% versus 18%, P < 0.01) and in the setting of
      atherosclerotic heart disease for detecting wall motion abnormalities (14% versus
      5%, P < 0.01). CONCLUSION: Diagnostic yield of echocardiography is similar when
      ordered by internists and cardiologists. With the information obtained,
      management is altered in a slightly greater proportion of cases involving a
      cardiologist. This may be due to utilization of echocardiography more often for
      estimating left ventricular function and for detecting wall motion abnormalities
      by cardiologists.

PMID- 9003105
TI  - Usefulness of a quantitative analysis of the recovery phase patterns of the ST
      segment depression in the diagnosis of coronary artery disease.
AB  - PURPOSE: To assess the diagnostic value of the recovery phase patterns of the ST
      segment depression in patients referred for chest pain. PATIENTS AND METHODS:
      Continuous plots of ST-segment depression against heart rate during exercise and
      recovery were constructed within a population of 160 consecutive symptomatic
      patients who all had undergone catheterization (80 with > or = 1 stenosis > or =
      50%). We used a new quantitative method of measurement allowing all kinds of rate
      recovery loops (even the so-called "intermediate" loops) to be considered for
      analysis. The measurements of the heart rate (HR)-adjusted ST-segment depression
      were performed at 20 and 60 ms from the J point, providing two different values
      of a quantified recovery loop index (RLI): RLI 20 and RLI 60. RESULTS: Both RLI
      showed a higher specificity (0.81 +/- 0.04 and 0.74 +/- 0.05, respectively) than
      did the standard criterion (0.65 +/- 0.10), but the difference was significant
      regarding RLI 20 only (P = 0.011). As to the sensitivity, no significant
      differences were found among all of the criteria (0.74 +/- 0.05, 0.80 +/- 0.04,
      0.76 +/- 0.05, respectively). The timing of measurements of the RLI within the
      repolarization phase did not affect their overall accuracy (0.77 +/- 0.03 for
      both RLI). The values of the receiver-operating characteristic (ROC) curve areas
      were significantly greater for both RLI (0.83 +/- 0.06 and 0.84 +/- 0.06
      respectively) than for the standard criterion (0.75 +/- 0.07; P < 0.02). Finally,
      both RLI allowed to differentiate accurately the study subjects according to the
      number of diseased vessels, whereas the standard criterion could only distinguish
      between CAD patients and subjects with normal angiograms. CONCLUSION: The
      quantitative analysis of the rate recovery phase patterns appears to be useful
      for the diagnosis of coronary heart disease and the assessment of its severity in
      symptomatic patients.

PMID- 9003106
TI  - Etiology of esophageal disease in human immunodeficiency virus-infected patients
      who fail antifungal therapy.
AB  - PURPOSE: To determine the etiologies of esophageal symptoms in human
      immunodeficiency virus (HIV)-infected patients failing antifungal treatment.
      METHODS: Between August 1, 1990 and December 31, 1994, all HIV-infected patients
      seen at a large inner-city hospital who had esophageal complaints despite being
      on antifungal therapy were prospectively evaluated for the cause of symptoms.
      Thus, the population studied included patients given empiric antifungal therapy
      for esophageal symptoms and patients who developed symptoms while on long-term
      antifungal therapy. Endoscopy was performed in all patients. The cause of
      symptoms was determined by the clinical, endoscopic, and pathologic findings, and
      follow-up after treatment. RESULTS: Over the 53-month study period, 74 patients
      failing empiric antifungal therapy were identified. The majority (77%) of these
      patients had esophageal ulcers; 25 patients had idiopathic ulcers and 24 had
      cytomegalovirus. In 2 patients, Candida was present with other causes of
      ulcerative esophagitis. Candida esophagitis alone was diagnosed in only 3
      patients. No endoscopic abnormalities were observed in 14 patients (19%). An
      additional 24 patients developed esophageal symptoms while receiving antifungal
      therapy; endoscopic findings in these patients included ulceration in 16 (67%),
      Candida esophagitis alone in 2, and normal in 6. Empirically treated patients in
      whom odynophagia was not the only symptom, those with dysphagia alone, and those
      with a CD4 count > 100/mm3 were less likely to have an endoscopic diagnosis.
      CONCLUSIONS: Esophageal ulceration is the most common cause of esophageal
      symptoms in HIV-infected patients failing empiric antifungal therapy and those
      developing symptoms while receiving antifungal agents. Given these findings,
      endoscopy should be the test of choice for these nonresponders, rather than
      escalating the dose of antifungal agent, adding other empiric treatments, or
      performing barium esophagography.

PMID- 9003107
TI  - The importance of comorbidity in HIV-infected patients over 55: a retrospective
      case-control study.
AB  - PURPOSE: To study the impact of comorbidity on the course of HIV disease in older
      patients as compared to a matched cohort of younger patients. METHODS: In a
      retrospective case-control study, we compared 43 HIV-infected patients > 55 years
      old to a randomly selected cohort of 86 patients < 45 years old, matched by date
      of HIV diagnosis. We collected data on non-HIV-related morbidity (as assessed by
      the Charlson comorbidity index), initiator of HIV testing, HIV stage at time of
      HIV diagnosis (TOHD), AIDS defining diagnoses, AIDS-related illnesses (ARI),
      observed AIDS-free interval, survival, and frequency of HIV-related and unrelated
      hospitalizations. RESULTS: The older cohort was more likely to have had HIV
      testing initiated by a health care provider (36 of 36 versus 50 of 66, P =
      0.003), and to have acquired HIV from a transfusion (5 of 43 versus 0 of 86, P =
      0.001), had lower CD4 cell counts at TOHD (205 versus 429, P = 0.02), a shorter
      observed AIDS-free interval (24.0 versus 52.8 months, P = 0.0002) and a shorter
      survival (28.2 versus 58.9 months, P = 0.0002). The older cohort had more HIV
      related (13.4 versus 9.2 per 100 patient-months, P = 0.024) and non-HIV-related
      hospitalizations (12.9 versus 8.1 per 100 patient-months, P = 0.0001). The
      comorbidity index was significantly higher in the older cohort (0.907 versus
      0.198, P = 0.0001) and was a strong predictor of mortality, independent of age
      group (risk ratio = 1.38 per comorbidity point, P = 0.0003). CONCLUSIONS: Older
      HIV-infected patients presented with more advanced disease, which may have been
      due to lack of HIV awareness in this population. Older patients had a shorter
      observed AIDS-free interval and shorter survival. In addition, they had more HIV-
      and non-HIV-related comorbidity. The more rapid course and decreased survival in
      the elderly may be related to the increase in comorbidity.

PMID- 9003108
TI  - Increasing influenza immunization among high-risk patients: education or
      financial incentive?
AB  - PURPOSE: To determine whether an educational brochure or a lottery-type incentive
      increases influenza immunization rates. PATIENTS AND METHODS: In a prospective,
      single-blind factorial design randomized trial at an urban community health
      center, all high-risk patients (n = 797) seen in the preceding 18 months were
      randomly assigned to one of four groups: a control group; a group mailed a large
      print, illustrated educational brochure emphasizing factors important to patients
      in making a decision about influenza immunization; a group mailed a lottery-type
      incentive announcing that all patients receiving influenza immunization would be
      eligible for grocery gift certificates; and a group mailed both educational
      brochure and incentive. Immunization was free, available without an appointment,
      and recorded by a computerized tracking system. RESULTS: The group mailed the
      brochure was more likely to be immunized than control (odds ratio [OR] = 2.29,
      95% confidence interval [CI] 1.45 to 3.61), as was the group mailed the incentive
      (OR = 1.68, 95% CI 1.05 to 2.68), but there was no difference between the group
      mailed both interventions and the control group. The effectiveness of the
      brochure was more striking for individuals who had not accepted immunization in
      the prior year (OR = 4.21, 95% CI 2.48 to 7.14), suggesting a true educational
      effect rather than simply a reminder. CONCLUSION: In this community health center
      setting, an illustrated educational brochure increased influenza immunization
      among high-risk patients, a lottery-type incentive was much less effective, and
      both together was not effective.

PMID- 9003109
TI  - Predictors of prognosis and risk of acute renal failure in patients with Rocky
      Mountain spotted fever.
AB  - BACKGROUND: Acute renal failure has long been associated with severe Rocky
      Mountain spotted fever (RMSF). Despite many descriptions of the protean
      manifestations of this disease, relatively little is known concerning the risk
      factors for acute renal failure. Only a few studies have examined the outcome of
      patients infected with Rickettsia rickettsii who develop renal insufficiency, and
      these studies had methodological problems. OBJECTIVE: To study the incidence,
      risk factors, and outcomes of acute renal failure in a large group of
      hospitalized patients with definite or probable RMSF. METHODS: The clinical
      records of 114 patients with definite or probable RMSF were retrospectively
      reviewed to identify clinical and biochemical abnormalities at the time of
      admission that were associated with the development of acute renal failure and
      subsequent mortality. Renal failure was defined as a serum creatinine (Cr) above
      2 mg/dL. Logistic regression was used to study the association between these
      variables and the outcomes during hospitalization: death and the development of
      acute renal failure. RESULTS: The mortality rate in this series was 14%; 19% of
      the patients developed acute renal failure. The development of acute renal
      failure increased the odds ratio (OR) of dying by a factor of 17 (P = 0.001).
      Factors at the time of hospitalization that were associated at a univariate level
      with subsequent mortality included elevated serum Cr, increased age, increased
      level of AST, increased level of bilirubin, decreased serum sodium and platelet
      count, the presence of neurological involvement, and being male. Both the
      presence of neurological involvement and an elevated serum Cr at presentation
      were independently associated with increased mortality by multivariate analysis.
      Three patients developed acute renal failure that required hemodialysis, and only
      1 of these 3 patients survived; he was ultimately discharged with a normal serum
      Cr. Factors at presentation that were associated with the development of acute
      renal failure included increased bilirubin, increasing age, thrombocytopenia, and
      the presence of neurological involvement. Both age and decreased platelet count
      at presentation were independently associated with the development of acute renal
      failure by multivariate analysis. CONCLUSION: Acute renal failure was a frequent
      complication of RMSF in this series of patients from a tertiary referral medical
      center. The presence of acute renal failure was strongly associated with death.
      Clinical and biochemical variables are useful in predicting which patients will
      develop acute renal failure.

PMID- 9003110
TI  - Pravastatin reduces carotid intima-media thickness progression in an asymptomatic
      hypercholesterolemic mediterranean population: the Carotid Atherosclerosis
      Italian Ultrasound Study.
AB  - PURPOSE: The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was
      performed to test the effects of lipid lowering on the progression of carotid
      intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean
      country. PATIENTS AND METHODS: Eligibility included hypercholesterolemia
      (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density
      lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the
      carotid arteries. Patients (mean age 55 years, 53% male) were assigned to
      pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound
      imaging was used to quantify IMT at baseline, and semiannually thereafter for up
      to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each
      patient visit, and used to determine each patient's longitudinal progression
      slope. The intention-to-treat group difference in the MMaxIMT progression was
      chosen a priori as the primary end point. RESULTS: Five serious cardiovascular
      events (1 fatal myocardial infarction), and 7 drop-outs for cancer were
      registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus 
      0.01 in the placebo group, and remained substantially unchanged afterward (-0.23
      versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/
      0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the
      placebo and pravastatin groups, respectively. IMT progression slopes diverged
      after 6 months of treatment. CONCLUSIONS: Pravastatin stops the progression of
      carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This
      finding extends the beneficial effects of cholesterol lowering to the primary
      prevention of atherosclerosis in a population with relatively low cardiovascular
      event rates, and suggests that this benefit is mediated by specific morphological
      effects on early stages of plaque development.

PMID- 9003111
TI  - Familial medullary thyroid carcinoma: not a distinct entity? Genotype-phenotype
      correlation in a large family.
AB  - BACKGROUND: Multiple endocrine neoplasia type 2A (MEN 2A) is a hereditary
      syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma,
      and hyperparathyroidism. Familial MTC (FMTC) is characterized by MTC only. Both
      MEN 2A and FMTC are caused by germline mutations of the RET proto-oncogene.
      PURPOSE: To assess genotype/phenotype correlations, large families have to be
      examined periodically over a long period using an extensive screening program.
      PATIENTS AND METHODS: Since 1973, we screened a large family with hereditary C
      cell carcinoma for MTC, pheochromocytoma, and parathyroid disease by clinical
      tests and imaging methods. A germline codon Cys618 to Ser mutation in the RET
      proto-oncogene was recently identified in this family. The disease phenotype
      associated with this mutation was compared with that of Cys634 mutations in some
      other large MEN 2A families. RESULTS: The distinct course of disease in the
      family described here is similar to that in other FMTC families and MEN 2A
      families with a Cys618 mutation of the RET gene, but clearly different from that
      in families with a Cys634 mutation. The frequency of pheochromocytomas and
      parathyroid disease is clearly lower, whereas cure rates and life expectancy are
      higher. However, in families with a Cys618 mutation, pheochromocytoma and
      parathyroid disease do occur. CONCLUSION: In FMTC families with cysteine codon
      mutations of the RET proto-oncogene, screening for other endocrinopathies is
      mandatory, since these may not be MTC-only families. Therefore, we suggest that
      MEN 2A families should not be subclassified into MEN 2A and FMTC, but rather
      according to their specific mutation in the RET protein (i.e., for this family
      MEN 2A RET C618S).

PMID- 9003112
TI  - Arthritis of systemic disease.

PMID- 9003114
TI  - Problems of professionalism: physician impairment.

PMID- 9003113
TI  - General internists influence students to choose primary care careers: the power
      of role modeling.
AB  - PURPOSE: To determine whether medical students supervised by general internist
      attendings during the third-year medicine clerkship are more likely to choose
      primary care careers than students supervised by subspecialist attendings.
      METHODS: One hundred forty-four consecutive medical students rotating on the
      general medicine inpatient service during the 1993-1994 academic year were
      surveyed about their career choice and professional expectations, both at the
      beginning and end of the clerkship; an additional 50 students completed a post
      clerkship survey only. The cohort of students was surveyed at graduation to
      determine stability of their career preferences. RESULTS: Both pre- and post
      clerkship surveys were completed by 138 of 144 students (96%); post-clerkship
      surveys were completed by 181/194 (93%); and graduation surveys were completed by
      137/188 (73%). Fifty-eight students (32%) designated primary care (general
      internal medicine, general pediatrics, or family practice) as their career choice
      post-clerkship; of these, 45 students (78%) also indicated a primary care career
      choice at graduation. Characteristics associated with choosing primary care post
      clerkship were: low income expectation, desire to interact closely with patients,
      desire to contribute to society, low class rank, female gender, and high
      educational debt. Having a physician parent was negatively associated with
      choosing primary care. After controlling for important demographic, academic and
      attitudinal characteristics, increasing exposure to a general internist attending
      was associated with choosing primary care (OR = 5.1, comparing highest to lowest
      amount). Among students choosing primary care, exposure to a general internist
      attending was associated with choosing general internal medicine in a dose
      dependent fashion (OR = 4.2, comparing highest to lowest amount). CONCLUSIONS:
      Although career choice is clearly related to personal characteristics such as
      socioeconomic background and humanistic qualities, a high degree of exposure to
      general internists during the medicine clerkship is associated with choosing
      primary care. Exposure of students interested in primary care to general
      internist attendings may also influence them to consider general internal
      medicine over family practice and pediatrics.

PMID- 9003115
TI  - Detection of HHV-8 in Sjogren's syndrome.

PMID- 9003117
TI  - Near end-of-life care preferences.

PMID- 9003118
TI  - Intensity of murmur and severity of regurgitation.

PMID- 9003116
TI  - Adynamic ileus in a patient with non-small-cell lung cancer after treatment with
      vinorelbine.

PMID- 9003119
TI  - New directions for community intervention studies.

PMID- 9003120
TI  - Drug use and behavior change.

PMID- 9003121
TI  - Annotation: patients on the auction block.

PMID- 9003122
TI  - Annotation: preventive screening for health risks among adolescents.

PMID- 9003123
TI  - Comment: genetics and public health.

PMID- 9003124
TI  - CDC's first 50 years: lessons learned and relearned.

PMID- 9003125
TI  - The cost-effectiveness of HIV prevention targeting: how much more bang for the
      buck?
AB  - BACKGROUND: Although the targeting of human immunodeficiency virus (HIV)
      prevention to high-risk populations has been widely discussed, its benefits have
      not been quantified. METHODS: This analysis of cost-effectiveness combines an HIV
      epidemic model, target population scenarios, and data on the cost and impact of
      prevention. RESULTS: The number of HIV infections averted in 5 years with $1
      million in annual prevention spending ranges from 164 in high-risk populations to
      0.4 in very-low-risk populations. Fortyfold to two-hundredfold differences in
      prevention costs could equalize HIV infections averted. CONCLUSIONS: Targeting
      appears to provide substantial benefit and should be considered in allocation
      decisions about prevention.

PMID- 9003126
TI  - Some principles in study design for preventing HIV transmission: rigor or
      reality.

PMID- 9003128
TI  - Estimating the indirect cost of illness: an assessment of the forgone earnings
      approach.
AB  - OBJECTIVES: This study attempted to assess (1) the accuracy of estimates of the
      indirect cost of illness and death computed with the human capital (forgone
      earnings) method and (2) the sensitivity of these estimates to key assumptions
      and parameters. METHODS: The study used data from the annual Current Population
      Surveys of 1964 through 1988 to compare the earnings experience of cohorts of
      White men aged 18 through 65 with predictions made with the human capital method.
      The study then assessed the sources and magnitude of the observed differences.
      RESULTS: Predictions of forgone earnings can be as much as 18% greater or 20%
      smaller than actual earnings, under identical assumptions, depending on the data
      used. While in most cases errors are quite small, alternative, equally plausible
      estimates of forgone earnings may differ by as much as 50%. Estimates differed
      mainly because of (1) the cross section chosen to make the predictions and (2)
      assumptions about future earnings growth. However, other factors, such as cohort
      size, also contributed to variation. CONCLUSIONS: Researchers and policymakers
      should be very careful in making and interpreting estimates of the indirect cost
      of illness and death.

PMID- 9003127
TI  - From genes to public health: the applications of genetic technology in disease
      prevention. Genetics Working Group.
AB  - OBJECTIVES: With advances in the Human Genome Project, the implications of
      genetic technology in disease prevention should be assessed. METHODS: The
      paradigm suggested in The Future of Public Health--assessment, policy
      development, and assurance--was used to examine the continuum from genetic
      technology to public health practice. RESULTS: First, important public health
      functions are to (1) assess the impact of genes and their interactions with
      modifiable disease risk factors on the health status of the population and (2)
      assess the impact and safety of genetic testing on the population. Second, given
      the many implications of genetic testing, the public health community should
      participate in policy development related to the timing and use of genetic
      testing in disease prevention. Third, whenever appropriate, the public health
      community needs to ensure the development of public health genetics programs
      (e.g. newborn screening) and evaluate the quality and effectiveness of the use of
      genetic testing in disease prevention. CONCLUSIONS: Although most current genetic
      tests are not ready for disease prevention, there is an important role for the
      public health community in translating genetic technology into disease
      prevention.

PMID- 9003129
TI  - Trends in overweight among US adults from 1987 to 1993: a multistate telephone
      survey.
AB  - OBJECTIVES: Using data from the Behavioral Risk Factor Surveillance System, this
      study describes trends in the prevalence of overweight between 1987 and 1993.
      METHODS: Data were examined from 33 states participating in an ongoing telephone
      survey of health behaviors of adults (n = 387,704). Self-reported weights and
      heights were used to calculate sex-specific prevalence estimates of overweight
      for each year from 1987 to 1993. Time trends were evaluated with the use of
      linear regression. RESULTS: Between 1987 and 1993, the age-adjusted prevalence of
      overweight increased by 0.9% per year for both sexes (from 21.9% to 26.7% among
      men and from 20.6% to 25.4% among women). The increasing linear trend was
      observed in all subgroups of the population but was most notable for Black men
      (1.5% per year) and men living in the Northeast (1.4% per year). Secular changes
      in smoking and leisure-time physical activity did not entirely account for the
      increase in overweight. CONCLUSIONS: The prevalence of overweight among American
      adults increased by 5% between 1987 and 1993. Efforts are needed to explore the
      causes of this adverse trend and to find effective strategies to prevent obesity.

PMID- 9003130
TI  - Cocaine use and characteristics of young adult users from 1987 to 1992: the
      CARDIA Study. Coronary Artery Risk Development in Young Adults.
AB  - OBJECTIVES: This study examined the relationship of sociodemographic factors and
      use of substances other than cocaine to cocaine use from 1987 to 1992 in a cohort
      of Black and White men and women 20 to 32 years of age. METHODS: Data were
      collected as part of the Coronary Artery Risk Development in Young Adults study.
      Self-reported cocaine use was analyzed through chi-square tests and repeated
      measures analyses of variance to determine the bivariate and multivariate
      relationships of sociodemographics and substance use behaviors to cocaine use
      over the 5-year period. RESULTS: Cocaine use declined in Whites but remained
      stable in Blacks from 1987 to 1992. Cross-sectional results showed that use was
      related to being Black, male and in the older half of the cohort, single, and
      unemployed; it was also related to higher levels of other substance use in 1987
      and 1992. Over time, the magnitude and strength of the relationship were
      consistent for each variable except for increased odds of cocaine use among the
      unemployed and Blacks in 1992. CONCLUSIONS: Sociodemographic characteristics and
      substance use behavior consistently identify individuals at risk for cocaine use.
      As a result, intervention programs should be targeted at these high-risk groups.

PMID- 9003131
TI  - Faithful patients: the effect of long-term physician-patient relationships on the
      costs and use of health care by older Americans.
AB  - OBJECTIVES: This study examined the impact of duration of physician-patient ties
      on the processes and costs of medical care. METHODS: The analyses used a
      nationally representative sample of Americans 65 years old or older who
      participated in the Medicare Current Beneficiary Survey in 1991 and had a usual
      source of care. RESULTS: Older Americans have long-standing ties with their
      physicians; among those with a usual source of care, 35.8% had ties enduring 10
      years or more. Longer ties were associated with a decreased likelihood of
      hospitalization and lower costs. Compared with patients with a tie of 1 year or
      less, patients with ties of 10 years or more incurred $316.78 less in Part B
      Medicare costs, after adjustment for key demographic and health characteristics.
      However, substantial impacts on the use of selected preventive care services and
      the adoption of certain healthy behaviors were not observed. CONCLUSIONS: This
      preliminary study suggests that long-standing physician-patient ties foster less
      expensive, less intensive medical care. Further studies are needed to confirm
      these findings and to understand how duration of tie influences the processes and
      outcomes of care.

PMID- 9003132
TI  - The timing of preventive services for women and children: the effect of having a
      usual source of care.
AB  - OBJECTIVES: This study investigated the causal effect of having a usual source of
      medical care on the timing of preventive services by women and children. METHODS:
      Data on 17,110 children and 23,488 women from the 1988 and 1990 National Health
      Interview Surveys were used to estimate ordered probit models of the effect of
      having a usual source of medical care on the time since the last receipt of each
      preventive service (routine checkups for children; blood pressure checks, Pap
      smears, and breast exams for adult women; mammograms for older women). Two-stage
      instrumental variables methods were used to eliminate simultaneity bias. RESULTS:
      The existence of a usual source of medical care was strongly correlated with the
      earlier receipt of preventive services, and the relationship appears to be causal
      for Pap smears, breast exams, and mammograms. However, there was little evidence
      that having a regular provider caused an increased rate of routine checkups for
      children or blood pressure checks for adult women. CONCLUSIONS: Delivery systems
      that encourage the development of long-term relationships with medical providers
      may increase cancer screening rates among women.

PMID- 9003133
TI  - Healthy behaviors among women in the United States and Ontario: the effect on use
      of preventive care.
AB  - OBJECTIVES: This study examined how several healthy behaviors among women in
      Ontario and the United States explained (1) the use of preventive health
      services, (2) differences in use between socioeconomic groups, and (3)
      differences in use between the two health systems. METHODS: 1990 data on women
      from the Ontario Health Survey (n = 22,985) and the US National Health Interview
      Survey (n = 19,092) were analyzed. A woman who avoided smoking and obesity, used
      seatbelts, and regularly engaged in aerobic exercise was defined as having a
      healthy lifestyle. Women were considered screened if they reported a mammogram or
      a breast exam within the previous year or a Pap smear within 2 years. RESULTS: A
      healthy lifestyle was more common in the United States than Canada among more
      highly educated groups (odds ratio [OR] = 1.40; 95% confidence interval [CI] =
      1.22, 1.60 for college educated) but less common in the United States for those
      with less than a high school education (OR = 0.52; 95% CI = 0.40, 0.67). Each
      additional unhealthy behavior decreased the odds of having undergone a mammogram
      in the previous year by 20%. However, adjusting for the number of unhealthy
      behaviors did not substantially change the relationship between socioeconomic
      status and use of preventive services. CONCLUSIONS: The number of healthy
      behaviors is an important measure of demand for preventive health services. This
      measure varies across country and socioeconomic group.

PMID- 9003135
TI  - Don't ask, they won't tell: the quality of adolescent health screening in five
      practice settings.
AB  - OBJECTIVES: This study examined the extent to which comprehensive, age
      appropriate adolescent health screening is undertaken in the clinical setting and
      whether the extent of such screening varies by setting. METHODS: Charts of
      adolescents 13 to 17 years old (n = 788) were randomly selected from five
      practice settings in Minneapolis, Minn. Each was assessed for the number of
      biomedical and sociobehavioral health risks screened. RESULTS: In no practice
      setting was there screening to the level recommended. The two teen clinics
      screened more extensively for behavioral, psychosocial, substance use and sexual
      behavior risks than the community family practice setting, which, in turn,
      screened more extensively than either the private family practice or private
      pediatric practice settings, which did not differ from each other. Age
      differences and gender accounted for only small amounts of variance in total
      number of health risks screened, whereas differences among practice settings
      accounted for a larger amount. CONCLUSIONS: Results suggest substantive
      deficiencies in private practice settings' implementation of preventive care
      screening protocols for adolescents.

PMID- 9003134
TI  - An adolescent tobacco-use prevention trial in orthodontic offices.
AB  - OBJECTIVES: This study examined the effect of an orthodontist-delivered tobacco
      use prevention program for adolescents. METHODS: Southern California orthodontic
      offices were randomly assigned to experimental (n = 77) and control (n = 77)
      groups. Randomly selected adolescents were interviewed at baseline and 2 years
      later (n = 15,644). Experimental offices received tobacco prevention training,
      anti-tobacco materials, and 50 cents for each anti-tobacco "prescription"
      written. RESULTS: The 30-day tobacco use 2-year incidence rates for the control
      and experimental groups were 12.6% and 12.0%, respectively; incidence rates for
      using tobacco more than 100 times were 7.6% and 6.8%. Differences between the
      groups did not reach significance. Mean prescription compliance was 64.4%. A
      multivariate logistic model, showed a significant dose response: patients who
      received more prescriptions had lower incidence rates than those who received few
      or none (10% vs 14%). CONCLUSIONS: Training, payment, and support did not ensure
      clinician compliance with prevention services. The dose effect suggests that
      replication under conditions that would ensure clinician compliance and
      statistical power would more thoroughly test clinicians' ability to prevent
      tobacco use.

PMID- 9003136
TI  - The long-term effects of a cardiovascular disease prevention trial: the Stanford
      Five-City Project.
AB  - OBJECTIVES: This study examined long-term effects of a health-education
      intervention trial to reduce the risk of cardiovascular disease. METHODS: Surveys
      were conducted in California in two treatment and two control cities at baseline
      (1979/1980), after the 6-year intervention (1985/1986), and 3 years later at
      follow-up (1989/1990). Net treatment/control differences in risk-factor change
      were assessed for women and men 25 to 74 years of age. RESULTS: Blood pressure
      improvements observed in all cities from baseline to the end of the intervention
      were maintained during the follow-up in treatment but not control cities.
      Cholesterol levels continued to decline in all cities during follow-up. Smoking
      rates leveled out or increased slightly in treatment cities and continued to
      decline in control cities but did not yield significant net differences. Both
      coronary heart disease and all-cause mortality risk scores were maintained or
      continued to improve in treatment cities while leveling out or rebounding in
      control cities. CONCLUSIONS: These findings suggest that community-based
      cardiovascular disease prevention trials can have sustained effects. However, the
      modest net differences in risk factors suggest the need for new designs and
      interventions that will accelerate positive risk-factor change.

PMID- 9003138
TI  - Promoting abstinence among relapsed chronic smokers: the effect of telephone
      support.
AB  - OBJECTIVES: The present study used telephone support both to sustain abstinence
      and to encourage renewed quit attempts in smokers who had completed an intensive
      smoking cessation clinic. METHODS: Subjects were hard-core smokers (n = 1083) who
      had attended a multisession cessation clinic. They were then assigned randomly to
      receive telephone support (intervention calls 3, 9, and 21 months after the
      targeted cessation clinic quit date) or no further intervention. RESULTS: In the
      intervention condition, subjects who relapsed were significantly more likely to
      resume abstinence (that is, to recycle) than those in the comparison condition at
      follow-up (6 months: 17.8% vs 11.3%; 24 months: 25.7% vs 18.2%). Telephone
      support was not effective in preventing relapse, and overall differences in
      abstinence outcome were not significant. CONCLUSIONS: The major hypothesis of the
      current study--that telephone support would enhance the resumption of abstinence-
      received partial support. However, there was no evidence either of an overall
      treatment effect or of an effect in preventing relapse. Telephone outreach may be
      more effective in the context of self-help or other less intensive interventions.

PMID- 9003137
TI  - The protective effect of AIDS-related behavioral change among injection drug
      users: a cross-national study. WHO Multi-Centre Study of AIDS and Injecting Drug
      Use.
AB  - OBJECTIVE: This study assessed the relationship between self-reported acquired
      immunodeficiency syndrome (AIDS) behavioral change and human immunodeficiency
      virus (HIV) serostatus among injection drug users. METHODS: The study sample
      involved 4419 injection drug users recruited from drug abuse treatment and
      nontreatment settings in 11 cities in North America, South America, Europe, Asia,
      and Australia. The World Health Organization multisite risk behavior
      questionnaire was used, and either blood or saliva samples for HIV testing were
      obtained. Subjects were asked, "Since you first heard about AIDS, have you done
      anything to avoid getting AIDS?" RESULTS: The protective odds ratio for
      behavioral change against being infected with HIV was 0.50 (95% confidence
      interval = 0.42, 0.59). While there was important variation across sites, the
      relationship remained consistent across both demographic and drug use history
      subgroups. CONCLUSIONS: Injection drug users are capable of modifying their HIV
      risk behaviors and reporting accurately on behavioral changes. These behavioral
      changes are associated with their avoidance of HIV infection.

PMID- 9003139
TI  - The School Enrollment-Based Health Insurance program: socioeconomic factors in
      enrollees' use of health services.
AB  - OBJECTIVES: The School Enrollment-Based Health Insurance program is designed to
      reduce financial barriers to children's health care use. This study sought to
      determine if any socioeconomic measures differed between enrollees with at least
      one health care encounter and those with no encounters. METHODS: Logistic
      regression was used to assess the impact of various predictors on the odds that a
      child would use health care services. RESULTS: Children receiving free insurance
      premiums were less likely to use health care than those receiving partial
      subsidy. African-American and Hispanic children were less likely than Whites to
      use health care. Age, sex, and months enrolled also influenced the likelihood of
      health care use. CONCLUSIONS: Financial and non-financial factors must be
      considered when developing children's health care programs.

PMID- 9003140
TI  - The late-stage diagnosis of colorectal cancer: demographic and socioeconomic
      factors.
AB  - OBJECTIVES: This study described factors related to colorectal cancer stage at
      diagnosis. METHODS: Logistic regression analyses were used on data from the New
      York State Tumor Registry and US Census area-level social class indicators.
      RESULTS: After the effects of other predictors were controlled for, the odds of
      late-stage cancer increased as age decreased; women and African Americans were
      significantly more likely to have late stage than men and Whites; and individuals
      living in areas of low socioeconomic status (SES) were significantly more likely
      to be diagnosed at late stage than those living in higher SES areas. Stratified
      analyses showed that living in a low SES area was the most important determinant
      of stage for all age, race, gender and source-of-care groups. CONCLUSIONS: While
      all populations would benefit from the systematic use of screening
      socioeconomically disadvantaged groups may also benefit from targeted screening.

PMID- 9003141
TI  - Self-rated health among Hispanic vs non-Hispanic white adults: the San Luis
      Valley Health and Aging Study.
AB  - OBJECTIVES: This study investigated whether objective health indicators explained
      lower self-rated health among Hispanics compared with non-Hispanic Whites. It
      also considered socioeconomic and cultural explanations. METHODS: Health ratings
      of 429 Hispanics and 583 non-Hispanic Whites aged 20 through 74 were analyzed
      with logistic regression. RESULTS: Illness indicators were found to be strongly
      correlated with self-rated health in both ethnic groups, but after such markers
      were controlled for, Hispanics remained 3.6 times more likely to report fair or
      poor health (95% confidence interval = 2.4, 5.3). Adjustment for socioeconomic
      factors accounted for a portion of Hispanics' lower health rating, but the
      strongest explanatory factor was acculturation. CONCLUSIONS: Because of cultural
      and economic influences on definitions of health, ethnic differences in self
      assessed health may not accurately reflected patterns resulting from objective
      health measurements.

PMID- 9003142
TI  - Assessing children's ultraviolet radiation exposure: the potential usefulness of
      a colorimeter.
AB  - OBJECTIVES: This study evaluated the colorimeter as an objective measure of
      children's ultraviolet (UV) radiation exposure. METHODS: Fifty-eight children,
      ages 6 to 9 years, attended two summer measurement sessions, with 46 attending a
      subsequent winter session. RESULTS: Comparisons between summer sessions for the
      L* scale showed that only the upper arm significantly changed in the tanner
      direction, while b* scale values indicated significant tanning for all body
      sites. All exposed body sites changed significantly in the less tan direction
      between summer and winter measurements. CONCLUSIONS: Using colorimeters to
      objectively measure children's UV exposure has potential applications for skin
      cancer prevention programs.

PMID- 9003143
TI  - Compliance with antihypertensive therapy among elderly Medicaid enrollees: the
      roles of age, gender, and race.
AB  - OBJECTIVES: This study measured compliance and related demographic factors in a
      retrospective cohort of 4068 elderly outpatients newly starting antihypertensive
      therapy from 1982 through 1988. METHODS: Logistic regression modeling of data
      from the New Jersey Medicaid program was used. RESULTS: These patients filled
      antihypertensive prescriptions covering an average of only 179 days in the 365
      day follow-up period (49%) Good compliance (> or = 80%) was associated with
      advanced age (odds ratio [OR] = 2.12, for patients 85 or older) and White race
      (OR = 0.55 for Blacks). There was no relationship between compliance and gender.
      CONCLUSIONS: Despite the efficacy of antihypertensive therapy in preventing
      cardiovascular morbidity, such high rates of noncompliance may contribute to
      suboptimal patient outcomes.

PMID- 9003145
TI  - Inappropriately timed immunizations: types, causes, and their relationship to
      record keeping.
AB  - OBJECTIVES: This study examined inappropriately timed immunizations and their
      relationship to record keeping practices in Los Angeles public health centers.
      METHODS: Records of children's visits were reviewed at four public health centers
      maintaining separate records. RESULTS: One third of all children seen at both
      immunization-only and well child clinics were given inappropriately timed
      immunizations. Almost half of the immunizations were not transferred between sets
      of records. Children seen in both clinics were more than twice as likely to
      receive at least one inappropriately timed immunization as those seen only at the
      well child clinic. CONCLUSIONS: Keeping separate immunization records at separate
      clinics leads to inappropriately timed immunizations.

PMID- 9003144
TI  - Assessing mothers' attitudes about the physician's role in child health
      promotion.
AB  - OBJECTIVE: This study assessed maternal attitudes about the physician's role in
      child health promotion. METHODS: Home interviews were conducted with 200
      Massachusetts mothers (with one child age 2 to 3 years) enrolled in a health
      maintenance organization. RESULTS: Mothers chose growth and nutrition, physical
      development, and illness as the most important topics and felt that providers
      have the ability to prevent problems and to help. Psychosocial and safety issues
      were less important, although mothers felt susceptible to these issues and
      believed they greatly affected children's health. CONCLUSIONS: On all issues,
      mothers believed physicians were more effective in helping families after, not
      before, problems arose. The Health Belief Model provided insight into attitudes
      and possible interventions.

PMID- 9003146
TI  - Using social gatherings to encourage HIV risk reduction among drug users.

PMID- 9003147
TI  - An intervention with high-risk mothers who abuse alcohol and drugs: the Seattle
      Advocacy Model.

PMID- 9003148
TI  - Establishing an indigent health care clinic in an Indiana "healthy city".

PMID- 9003149
TI  - Montana County creates local solution to health care crisis.

PMID- 9003150
TI  - Peace in the Middle East: the implications for public health.

PMID- 9003151
TI  - Maine students' musculoskeletal injuries attributed to harvesting blueberries.

PMID- 9003152
TI  - Sexual identity vs sexual behavior.

PMID- 9003153
TI  - Lowering infant mortality in western Europe: national health service vs social
      security systems.

PMID- 9003154
TI  - Intensive chemotherapy for adult acute lymphoblastic leukaemia given with or
      without granulocyte-macrophage colony stimulating factor.
AB  - Twenty-six patients with newly diagnosed ALL (age range 15-49 years, median 32
      years) received treatment comprising: cycles 1 and 2: adriamycin 30 mg/m2 days 1
      3, vincristine: 2 mg days 1, 8, and 15, with prednisolone 40 mg daily, given
      until complete remission (CR). L-asparaginase 10000 units/m2, days 1-14, was
      given only with the first cycle. Cycle 3 consisted of 100 mg/m2 etoposide orally,
      days 1-5, and 1 gm/m2 bd cytosine arabinoside (ara-C) days 1-5. Cycles 1-3 were
      then repeated. Intrathecal methotrexate (MTX) 12.5 mg was given on day 1 of each
      treatment cycle. The first 12 consecutive patients received this chemotherapy
      alone, the subsequent 14 received, in addition, 3 micrograms/kg GM-CSF
      subcutaneously, from day 4 of cycles 1,2,4 and 5 (and from day 6 of cycles 3 and
      6) until the absolute neutrophil count had reached 0.5 x 10(9)/1. All patients in
      whom CR was achieved then received prophylactic cranial irradiation. With the
      exception of those with T-ALL, this was followed by oral maintenance therapy
      consisting of 6-mercaptopurine, MTX, and cyclophosphamide for 3 years. Patients
      receiving GM-CSF did not have shorter intercycle times or a lower incidence of
      documented infections than those who did not receive it. The CR rate was 89%
      overall-uninfluenced by GM-CSF, but higher than that achieved previously at St
      Bartholomew's Hospital in an equivalent age-group.

PMID- 9003156
TI  - High-dose therapy followed by bone marrow transplantation for relapsed follicular
      non-Hodgkin's lymphoma. Dutch HOVON Group.
AB  - PURPOSE: To analyze whether, in addition to survival, and disease-free survival
      progression-free interval after transplantation would be longer than the last
      progression-free interval before transplantation, supporting the argument that
      high-dose therapy may change the biologic behavior of the disease. PATIENTS AND
      METHODS: Patients with a poor-risk relapsed follicular NHL were treated with
      three cycles of doxorubicin 50 mg/m2 and teniposide 60 mg/m2, followed by
      etoposide 350 mg/m2, cyclophosphamide 60 mg/kg, and TBI and unpurged BMT.
      RESULTS: Twelve patients were entered in the study. Ten patients fulfilled the
      criteria for response and underwent transplantation, two of them with an
      allograft. Nine of ten patients with transplants achieved a complete remission
      after BMT. One patient died on day 41 due to veno-occlusive disease. The nine
      patients with transplants who were evaluable for follow-up had a conversion of
      remission or response duration after transplantation, their progression-free
      interval after BMT being superior to the last one before BMT with a median of
      1044 + days. Overall survival and disease-free survival in the transplant
      patients after a median follow-up of 1160 days from BMT is 90%. CONCLUSION: High
      dose chemotherapy followed by stem cell rescue may change the clinical course in
      follicular non-Hodgkin's lymphoma patients.

PMID- 9003155
TI  - FLAG (fludarabine, cytosine arabinoside, G-CSF) for refractory and relapsed acute
      myeloid leukemia.
AB  - Twenty-two patients with refractory or relapsed AML were treated with FLAG [25
      mg/m2 fludarabine daily (days 1-5), 2 g/m2 daily Ara-C (days 1-5) and 400
      micrograms/m2 daily G-CSF (day -1 till the absolute neutrophil count was >
      500/microliter)]. Median age was 46 years (range 24-63). Eight patients had
      leukemia which was primarily refractory to conventional regimens, six were in
      first, seven were in second, and one was in third relapse. Overall, 11 of 22
      (50%) patients achieved complete remission (CR), three had a partial response
      (PR), and seven did not respond (NR). One patient died of an early cerebral
      hemorrhage. The median remission duration from achievement of CR after FLAG was
      9.9 months and median survival was 13.0 months. One patient is alive in CR at
      31.9 months. Hematological toxicity of the regimen was severe. The median time to
      neutrophil recovery (ANC > 500/microliter) was 21 days (range 18-33). A median of
      seven red cell units (range 0-22) and of six platelet concentrate units (range 3
      28) had to be given. Median duration of febrile neutropenia was 2 days (range 0
      20 days) and patients were on i.v. antibiotics for a median of 16 days (range 0
      51). There was no death from infection. Nonhematological toxicity was remarkably
      low, with almost no neurotoxicity and no major hepatotoxicity. In conclusion,
      FLAG seems to be an efficient and well tolerated regimen. It may be particularly
      useful for patients who have a sibling or unrelated donor for subsequent
      allogeneic bone marrow transplantation.

PMID- 9003157
TI  - Continuous low-dose subcutaneous desferrioxamine (DFO) to prevent allergic
      manifestations in patients with iron overload.
AB  - In some patients compliance to subcutaneous desferrioxamine therapy is reduced
      because of allergic symptoms. Effective drug desensitization consists of bringing
      patients to tolerate the same mode of administration. We evaluated three
      thalassemic patients with severe allergies to desferrioxamine. Each patient
      received weekly three prefilled infusors with desferrioxamine 4 g/48 m1/48 h for
      s.c. therapy. Follow-up was performed for 12 consecutive weeks. During follow-up
      no allergic events were noted. The s-ferritin levels decreased from 2583
      micrograms/l +/- 485 to 1916 micrograms/l +/- 275 (mean decrease 25.8%, p =
      0.038). Compliance to the infusional system was excellent. Our results show that
      continuous infusion of desferrioxamine using a new infusional delivery system is
      effective in preventing allergic reactions and in reducing iron overload.

PMID- 9003158
TI  - Thrombophilia in ethnic Arabs in Kuwait.
AB  - One hundred and thirty unrelated patients with recurrent deep venous thrombosis
      were studied over a period of 4 years (1986-1990) in order to determine the
      possible etiology. Protein C levels were estimated in plasma both by chromogenic
      substrate assay and by immunoassay. Protein S levels in plasma was determined by
      immunoassay using antisera to human protein S. Antithrombin III (AT-III) was
      assayed using monospecific rabbit antiserum to human AT-III. Fifteen patients
      were found to have hereditary protein C deficiency (11.52%). Family studies
      revealed autosomal recessive inheritance in one patient and a dominant pattern in
      the remaining 14 patients. Protein S deficiency was found in eight cases (6.1%),
      AT-III deficiency was established in five cases (3.8%) and a fibrinolytic defect
      in 33 cases (25.4%). Thrombosis of visceral and cerebral vessels and a positive
      family history were more frequently found among patients who had hereditary
      deficiency of one or the other antithrombotic factor. Thrombophlebitis of
      superficial veins was found to be very common in patients with protein C and
      protein S deficiency and virtually absent in AT-III deficiency. The high
      frequency of protein C and protein S deficiency in this ethnic group is
      attributed to the high frequency of consanguinity.

PMID- 9003159
TI  - Philadelphia chromosome-positive secondary acute myeloid leukemia following high
      dose chemotherapy with peripheral blood progenitor cell support for relapsed low
      grade non-Hodgkin's lymphoma.
AB  - We report the case of a 47-year-old patient who developed acute myelogenous
      leukemia (AML) 18 months after receiving high-dose chemotherapy with peripheral
      blood progenitor cell support (PBPCT) for relapsed low-grade follicular non
      Hodgkin's lymphoma (NHL). Cytogenetic analysis of the leukemic cells showed the
      translocation (9;22)(q34;q11). In three mitoses, an additional Philadelphia
      chromosome (Ph1) was present. In the literature, Philadelphia chromosome-positive
      secondary AML has been described only once before in a patient with multiple
      myeloma.

PMID- 9003160
TI  - Treatment of angioimmunoblastic lymphadenopathy with dysproteinemia using 2
      chlorodeoxyadenosine.
AB  - Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is an atypical
      lympho-proliferative disorder with borderline features that often constitute a
      diagnostic challenge for the hematopathologist and a therapeutic dilemma for the
      treating clinician. Morphologically, the involved lymph nodes in this disorder
      are characterized by abnormal infilitration by immunoblasts and plasma cells,
      often in clusters or sheets. Regressed follicles may be seen; these are referred
      to as "burned out." Neovascularization is prominent, and a background of
      inflammatory cells is usually present. AILD was originally thought to represent
      an exaggerated autoimmune response. Because of the short median survival of the
      patients and the demonstration of T-cell clonality, AILD now is considered an
      aggressive lymphoma and is recognized as a subset of peripheral T-cell lymphoma
      by the REAL classification. In this article we present a patient with AILD who
      achieved durable partial remission after treatment with one cycle of 2
      chlorodeoxyadenosine.

PMID- 9003161
TI  - Pathologic rupture of the spleen in hematologic malignancies: two additional
      cases.
AB  - Pathologic rupture of the spleen in hematologic malignancies is rare. We present
      two cases of splenic rupture which occurred in a man with a secondary high-grade
      non-Hodgkin's lymphoma and a woman with chronic lymphocytic leukemia (CLL). In a
      review of the literature, we have been able to identify 136 cases of pathologic
      splenic rupture since 1861; 34% have occurred in acute leukemias, 34% in non
      Hodgkin's lymphomas, and 18% in chronic myelogenous leukemia (CML). We find a
      male-to-female ratio of 3:1, with considerable differences for the specific
      diseases encountered. Pathologic rupture of the spleen has happened almost
      exclusively in adults and the ruptured spleens are generally moderately to
      severely enlarged. It seems that, apart from splenic infiltration by a
      hematologic disease, splenic infarcts and coagulation disorders (which have
      previously been advanced as the most important pathophysiologic factors leading
      to rupture), male sex, adulthood, severe splenomegaly, and cytoreductive
      chemotherapy may increase the risk for pathologic splenic rupture. We briefly
      discuss symptoms preceding the event, diagnostic possibilities, and the outcome
      with operative and conservative approaches.

PMID- 9003162
TI  - Daniel's fees.

PMID- 9003163
TI  - Association of vaginal ultrasound and urinary tract infection.

PMID- 9003164
TI  - Running and its effect on family life: a follow-up of spouses' perceptions.

PMID- 9003165
TI  - Asthma and panic disorder.
AB  - OBJECTIVE: To compare asthma attacks with panic attacks and identify
      discriminating symptoms. DESIGN: Survey, case-control study. SETTING: Tertiary
      care centers. PATIENTS: Convenience sample of 71 patients with panic disorder,
      with or without agoraphobia, and without medical illnesses; and 71 patients with
      asthma, cohort-matched from 407 patients to be demographically similar to the
      panic disorder sample. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Asthma Symptom
      Checklist. RESULTS: Clusters of symptoms reflecting panic-fear and
      hyperventilation-hypocapnia were more strongly endorsed by subjects with panic
      disorder, whereas airway obstruction symptom clusters were more strongly
      descriptive of asthma attacks (all P < .05). Three symptoms differentiated the
      groups with sensitivity greater than 0.90 and specificity greater than 0.70:
      wheezing, mucous congestion, and coughing, all being present significantly more
      among asthma attacks than panic attacks. CONCLUSION: Knowledge of what symptoms
      discriminate asthma attacks from panic attacks may help physicians identify each
      type of attack in individuals who experience both.

PMID- 9003166
TI  - Community preceptors' views of a required third-year family medicine clerkship.
AB  - BACKGROUND: Previous studies documented the importance of family medicine
      clerkships to medical student education and to the potential costs of precepting
      students borne by community physicians. But what are the physicians' views of
      their experience, their perceived needs for teaching, and sources of satisfaction
      from the preceptor role? OBJECTIVES: To explore preceptors' views of a required,
      third-year family medicine clerkship, focusing on satisfaction with the teaching
      experience, effect of having students in the practice, and concerns about
      continuing as a preceptor. METHODS: Preceptors from 38 private practices were
      asked to participate in a 15-minute telephone survey, using a semistructured
      interview format. RESULTS: Thirty-five physicians (92%) agreed to participate and
      33 of the 35 primary preceptors were interviewed. Of those interviewed, 29 (88%)
      indicated a positive teaching experience, and 31 (94%) desired to continue
      precepting. Intangible rewards (eg, love of teaching or "giving back" to the
      specialty of family medicine) far out-weighed tangible rewards (eg, dinners or
      letters of appreciation) with regard to their desire to precept. Continued
      satisfaction with precepting seemed to be affected by loss of revenue to the
      practice, longer work hours, ability to effectively manage time and patient load,
      and need for additional educational resources and equipment. CONCLUSIONS:
      Intrinsic rewards seem to be a key factor in the physicians' decision to precept.
      Moreover, to reinforce the preceptor's continued desire to precept, faculty
      development, provision of educational tools and resources, and remuneration may
      be necessary. Preceptors should be asked routinely about their needs, and special
      programs of support should be offered.

PMID- 9003167
TI  - Primary care physicians' practice patterns and diabetic retinopathy. Current
      levels of care.
AB  - BACKGROUND: Diabetic retinopathy is a costly and prevalent complication of
      diabetes mellitus. OBJECTIVE: To assess primary care physicians' self-reported
      practice patterns for the screening and detection of diabetic retinopathy
      relative to published guidelines. PARTICIPANTS AND METHODS: All primary care
      physicians (defined as general internists, family practitioners, and general
      practitioners) in Indiana were identified and surveyed using a mailed
      questionnaire. Of 2390 physicians, 1508 (63%) responded and were determined to be
      eligible. Of these 1508 physicians, 1058 (70%) completed all or some of the eye
      care-related questions. For each eye care practice, physicians were asked to
      specify the proportion of patients to which the practice was applied and the
      frequency (eg, every 3 months) with which the behavior was performed, if
      appropriate. Physicians were also asked to distinguish between patients with type
      I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus for
      each practice behavior. RESULTS: Physicians' responses were classified as "high,"
      "moderate," or "low" based on the American Diabetes Association guidelines. Forty
      five percent of the physicians' responses were classified as high for referring
      all of their patients with type I diabetes mellitus to an eye care specialist
      annually as were 35% of the physicians' responses for referring their patients
      with type II diabetes mellitus. Fewer physicians reported high levels of routine
      in-office funduscopic examination. No relationship was found between the extent
      to which physicians performed an in-office funduscopic examination and patterns
      of referral to eye care specialists. Logistic regression analysis suggested that
      recent graduates and general internists are most likely to report behavior that
      is considered high (P < .05). CONCLUSION: The diabetic retinopathy-related
      practice patterns of primary care physicians in Indiana differ significantly from
      published guidelines.

PMID- 9003168
TI  - Preventive health care for diabetics. A realistic vision.

PMID- 9003169
TI  - Are symptoms of anxiety and depression risk factors for hypertension?
      Longitudinal evidence from the National Health and Nutrition Examination Survey I
      Epidemiologic Follow-up Study.
AB  - OBJECTIVE: To test the hypothesis that symptoms of anxiety and depression
      increase the risk of experiencing hypertension, using the National Health and
      Nutrition Examination I Epidemiologic Follow-up Study. DESIGN: A cohort of men
      and women without evidence of hypertension at baseline were followed up for 7 to
      16 years. The association between 2 outcome measures (hypertension and treated
      hypertension) and baseline anxiety and depression was analyzed using Cox
      proportional hazards regression adjusting for hypertension risk factors (age;
      sex; education; cigarette smoking; body mass index; alcohol use; history of
      diabetes, stroke, or coronary heart disease; and baseline systolic blood
      pressure). Analyses were stratified by race and age (white persons aged 25-44
      years and 45-64 years and black persons aged 25-64 years). SETTING: General
      community. PARTICIPANTS: A population-based sample of 2992 initially normotensive
      persons. MAIN OUTCOME MEASURES: Incident hypertension was defined as blood
      pressure of 160/95 mm Hg or more, or prescription of antihypertensive
      medications. Treated hypertension was defined as prescription of antihypertensive
      medications. RESULTS: In the multivariate models for whites aged 45 to 64 years,
      high anxiety (relative risk [RR], 1.82; 95% confidence interval [CI], 1.30-2.53)
      and high depression (RR, 1.80; 95% CI, 1.16-2.78) remained independent predictors
      of incident hypertension. The risks associated with treated hypertension were
      also increased for high anxiety (RR, 2.36; 95% CI, 1.73-3.23) and high depression
      (RR, 1.89; 95% CI, 1.25-2.85). For blacks aged 25 to 64 years, high anxiety (RR,
      2.74; 95% CI, 1.35-5.53) and high depression (RR, 2.99; 95% CI, 1.41-6.33)
      remained independent predictors of incident hypertension. The risks associated
      with treated hypertension were also increased for high anxiety (RR, 3.24; 95% CI,
      1.59-6.61) and high depression (RR, 2.92; 95% CI, 1.37-6.22). For whites aged 25
      to 44 years, intermediate anxiety (RR, 1.62; 95% CI, 1.18-2.22) and intermediate
      depression (RR, 1.60; 95% CI, 1.17-2.17) remained independent predictors of
      treated hypertension only. CONCLUSION: Anxiety and depression are predictive of
      later incidence of hypertension and prescription treatment for hypertension.

PMID- 9003170
TI  - The tension in hypertension.

PMID- 9003171
TI  - Performance of gastrointestinal tract endoscopy by primary care physicians.
      Lessons from the US Medicare database.
AB  - Primary care physicians, including family physicians, often perform flexible
      sigmoidoscopy in their clinical practices. It is unknown how many of these and
      other endoscopic procedures, such as esophagogastroduodenoscopy and colonoscopy,
      are performed by these physicians. Therefore, physician reimbursement by the
      Medicare program was documented for selected endoscopic procedures during the
      calendar year 1993. Family physicians and general practitioners in the United
      States were reimbursed for 125,821 flexible sigmoidoscopies, 21,070 upper
      gastrointestinal tract endoscopic procedures, and 23,841 colonoscopies. General
      internists performed considerably more endoscopic procedures than did family
      physicians. Primary care physicians performed 44% of the reimbursable flexible
      sigmoidoscopies, 17% of upper gastrointestinal tract endoscopies, and 15% of
      colonoscopies in this patient group. In 1993, primary care physicians generated a
      total of $175 million in allowed charges by the Medicare program for
      gastrointestinal tract endoscopic procedures, of which $22.6 million was to
      general practitioners and family physicians. Family physicians, on average,
      charged less for gastrointestinal tract endoscopic procedures than did other
      physician specialists. Primary care physicians, especially general internists,
      are providing substantial numbers of gastrointestinal tract endoscopic services
      to their patients. As Medicare does not generally reimburse physicians to perform
      flexible sigmoidoscopy for colorectal cancer screening, it is likely that primary
      care physicians performed considerably more procedures than were documented in
      this study.

PMID- 9003172
TI  - Family medicine in Japan.
AB  - Two networks of medical care have grown up in Japan: 1 network based in hospitals
      and 1 based in private clinics. Most physicians in clinics practice general
      medicine, although only a small proportion of them are trained in primary care.
      Postgraduate medical education is oriented toward the training of specialists.
      Owing to the impending retirement of the cohort of clinic-based physicians who
      have dominated medical politics in Japan, the system is expected to change
      substantially in the next decade. Among the reformers is a small group of
      physicians who are attempting to introduce family practice.

PMID- 9003173
TI  - How to submit a specimen for cutaneous pathology analysis. Using the '5 D's' to
      get the most from biopsies.
AB  - Evaluation of cutaneous biopsy specimens is greatly assisted by appropriate
      clinical information from the submitting physician. Without such data, it is
      difficult if not impossible to accurately interpret some histologic findings. As
      such, the more dermatopathologists know about the patient from whom a biopsy
      specimen is being obtained the more accurate their interpretation of the
      histologic findings may be. We have listed 5 categories of information all
      beginning with the letter D, which should be available to dermatopathologists as
      they evaluate a cutaneous biopsy specimen-description, demographics, duration,
      diameter, and diagnosis. Inclusion of this information with skin biopsy specimens
      will assist in their accurate and timely interpretation.

PMID- 9003174
TI  - The relationship of self-esteem to the health-related behaviors of the patients
      of a primary care clinic.
AB  - To clarify the relationship of self-esteem and health-related behaviors of
      primary care clinic patients, 500 family practice residency patients were invited
      to complete self-esteem and health-risk appraisal instruments. Of the final
      subject pool (N = 469), 154 responded to the single-mailing solicitation, thereby
      yielding a 32.8% response rate. Correlational analysis found self-esteem to be
      associated with predicted longevity, life satisfaction, social ties, overall
      health, personal loss, seatbelt use, age, physical activity, smoking, exposure to
      violence, and substance use. Multiple regression analysis of male subjects' data
      found self-esteem most closely related to the frequency of exposure to danger,
      self-perceptions of health, and tobacco use. Similar analysis of the women's data
      most closely associated self-esteem to perceived social support, self-perception
      of health, diastolic blood pressure, and seatbelt use. The data clearly link
      individuals' self-esteem to predicted longevity. Those with greater self-regard
      were predicted to live longer, while those with poorer self-esteem achieved
      shorter predicted longevity. Contributing factors may have included greater
      emphasis on self-care.

PMID- 9003175
TI  - Self-esteem and health. Is the relationship real?

PMID- 9003176
TI  - Preferences of husbands and wives for prostate cancer screening.
AB  - The benefits of screening for prostate cancer are uncertain. Outcomes of
      treatment are particularly important to couples because they challenge the most
      intimate aspects of a couple's relationship. This study used clinical decision
      analysis to explore the preferences of 10 couples for prostate cancer screening.
      The decision-analytic model found that 7 of 10 husbands preferred the no
      screening strategy, while 9 of 10 wives preferred screening for their husbands.
      Wives associated little burden with complications of treatment, preferring to
      maximize their husbands' quantity of life regardless of complications. The issue
      of who is the decision maker is paramount in the case of prostate cancer
      screening. Optimal screening strategies may differ for husbands and wives.
      Guidelines for prostate cancer screening and management should consider assessing
      preferences on an individual couple basis.

PMID- 9003177
TI  - Whose life is it anyway?

PMID- 9003178
TI  - Reduction of firearm-related violence through firearm safety counseling. The role
      of family physicians.
AB  - The United States has a greater percentage of households with guns and more acts
      of violence than any other country in the western world. Suicide is the nation's
      eighth leading cause of deaths in the United States, of which 60% are caused by
      firearms. Homicide is the 11th leading cause of deaths among Americans, of which
      70% are caused by firearms. Another 1400 deaths each year are caused by
      unintentional firearm-related injuries. Most of these deaths can, in part, be
      attributed to inappropriate behaviors (eg, keeping a loaded and inadequately
      secured firearm in the home). As respected professionals in the community, family
      physicians have a unique opportunity to promote behaviors in patients that reduce
      the risk of firearm-related injuries in patients and their families.

PMID- 9003179
TI  - Femtosecond transient absorption study of carotenoid to chlorophyll energy
      transfer in the light-harvesting complex II of photosystem II.
AB  - Singlet energy transfer between the carotenoids (Cars) and chlorophylls (Chls) in
      the light-harvesting complex II (LHC II) from higher plants has been studied
      using ultrafast transient absorption spectroscopy by exciting the Cars directly
      in the 475-515 nm wavelength range. LHC II trimers from Arabidopsis thaliana with
      well-defined Car compositions have been used. From HPLC, the wild type (WT)
      monomer contains two luteins (Ls), one neoxanthin (N), and a trace of
      violaxanthin (V) per 12 Chls. The ABA-3 mutant contains 1.4 Ls and 0.6 zeaxanthin
      (Z) per monomer. Though exploitation of the difference in Car constitution and
      exciting the WT at 475 and 490 nm, and the ABA-3 mutant at 490 and 515 nm, the
      different Car contributions to energy transfer have been probed. Evidence for
      energy transfer mainly from the Car to Chl b is observed in the WT. In the
      mutant, additional transfer from Car to Chl a correlates with the presence of Z.
      The results imply predominant energy transfer from the central Ls to Chl b which
      requires a modification of the currently accepted arrangement of Chl pigments in
      LHC II.

PMID- 9003180
TI  - Truncation of the amino terminus of human apolipoprotein A-I substantially alters
      only the lipid-free conformation.
AB  - An amino-terminal deletion mutant (residues 1-43) of human apolipoprotein A-I
      (apo hA-I) has been produced from a bacterial expression system to explore the
      structural and functional role of these amino acids, encoded by exon 3, in apo hA
      I. Lipid binding of apo delta (1-43)A-I and lipid binding of apo hA-I are very
      similar as assessed by surface activity, lipid association with
      palmitoyloleoylphosphatidylcholine (POPC) vesicles, and lipid association with
      plasma lipoproteins. Preliminary kinetic measurements appear to show that the
      reactivity of lecithin:cholesterol acyltransferase (LCAT) with the mutant is
      slightly decreased compared to wild-type apo hA-I. Collectively, these results
      indicate that the N-terminal region is not necessary for lipid binding or
      activation of LCAT. In contrast, there are significant structural differences
      between lipid-free apo delta (1-43)A-I and apo hA-I, as judged by denaturant
      induced unfolding, binding of the fluorescent probe 1-anilinonaphthalene-8
      sulfonate, surface balance measurements, and far- and near-ultraviolet circular
      dichroic spectroscopy. All spectral and physical measurements indicate apo delta
      (1-43)A-I has a folded, tertiary structure, although it is significantly less
      stable than that of apo hA-I. It is concluded that the N-terminal 43 residues are
      an important structural element of the lipid-free conformational state of apo hA
      I, the absence of which induces a fundamentally different fold for the remaining
      carboxy-terminal residues, compared to those in native apo hA-I.

PMID- 9003181
TI  - Hepatocyte nuclear factor 4 inhibits the activity of site A from the rat
      apolipoprotein AI gene.
AB  - The pivotal role of apolipoprotein AI (Apo AI) in mediating reverse cholesterol
      transport has lead us to the study of transcription factors that influence the
      expression of this gene. Previous studies show that rat HNF-4 enhances the
      activity of a cis-acting site C in the rat Apo AI promoter. Since sites C and A
      share 80% homology, we have examined whether HNF-4 binds to and modulates the
      transcriptional activity of the A-motif. Results show that HNF-4 binds to site A.
      The transcriptional activity of site A in a human hepatoma cell line, HuH-7,
      increases 2-2.5-fold in the presence of antisense HNF-4, but the sense construct
      has no effect on the activity of the reporter template. The lack of an effect of
      HNF-4 on site A activity may be due to high endogenous levels of the factor in
      HuH-7 cells. However, in BHK cells HNF-4 clearly inhibits the transcriptional
      activity of site A. Together these findings suggest that in contrast to the
      enhancing effects of HNF-4 on site C, the same factor inhibits site A activity.
      Since hepatocytes normally contain the T3 receptor and this nuclear factor
      increases site A action, cotransfection of T3 receptor along with antisense HNF-4
      further augments the activity of p5'A.CAT. In summary, rat HNF-4 binds to site A
      from rat Apo AI DNA, and this factor suppresses site A activity. HNF-4 interferes
      with the enhancer role of the T3 receptor and thus contributes negatively to the
      net expression of the Apo AI gene.

PMID- 9003182
TI  - Conformation of T4 lysozyme in solution. Hinge-bending motion and the substrate
      induced conformational transition studied by site-directed spin labeling.
AB  - T4 lysozyme and mutants thereof crystallize in different conformations that are
      related to each other by a bend about a hinge in the molecule. This observation
      suggests that the wild type protein may undergo a hinge-bending motion in
      solution to allow substrate access to an otherwise closed active site cleft
      [Faber, H.R., & Matthews, B.W. (1990) Nature 348, 263-266]. To test this
      hypothesis, either single or pairs of nitroxide side chains were introduced into
      the protein to monitor tertiary contact interactions and inter-residue distances,
      respectively, in solution. A set of constraints for these structural parameters
      was derived from a reference state, a covalent enzyme-substrate adduct where the
      enzyme is locked in the closed state. In the absence of substrate, differences in
      both inter-residue distances and tertiary contact interactions relative to this
      reference state are consistent with a hinge-bending motion that opens the active
      site cleft. Quantitative analysis of spin-spin interactions between nitroxide
      pairs reveals an 8 A relative domain movement upon substrate binding. In
      addition, it is demonstrated that the I3P mutation, which produces a large hinge
      bending angle in the crystal, has no effect on the solution conformation. Thus,
      the hinge motion is not the result of the mutation but is an integral part of T4
      lysozyme catalysis in solution, as suggested recently [Zhang, X.J., Wozniak,
      J.A., & Matthews, B.W. (1995) J. Mol. Biol. 250, 527-552]. The strategy employed
      here, based on site-directed spin labeling, should be generally applicable to the
      study of protein conformation and conformational changes in solution.

PMID- 9003183
TI  - Dictyostelium discoideum myosin II: characterization of functional myosin motor
      fragments.
AB  - The transient kinetic properties of the recombinant myosin head fragments M761
      and M781, which both lack the light chain binding domain (LCBD) and correspond to
      the first 761 and 781 residues of Dictyostelium discoideum myosin II, were
      compared with those of the subfragment 1-like fragment M864 and a shorter
      catalytic domain fragment M754. The properties of M761, M781, and M864 are almost
      identical in regard to nucleotide binding, nucleotide hydrolysis, actin binding,
      and the interactions between actin and nucleotide binding sites. Only the rate of
      the hydrolysis step was significantly faster for M761 and the affinity of M781
      for actin significantly weaker than for M864. This indicates that the LCBD plays
      no major role in the biochemical behavior of the myosin head. In contrast, loss
      of the peptide between 754 and 761 produced several major changes in the property
      of M754 as documented previously [Woodward, S. K. A., Geeves, M. A., & Manstein,
      D. J. (1995) Biochemistry 34, 16056-16064]. We further show that C-terminal
      extension of M761 with one or two alpha-actinin repeats has very little effect on
      the behavior of the protein. The recombinant nature of M761 and the fact that it
      can be produced and purified in large amounts make it an ideal construct for
      systematic studies of the structure, kinetics, and function of the myosin motor.

PMID- 9003184
TI  - Effects of the intramolecular disulfide bond on ligand binding dynamics in
      myoglobin.
AB  - In order to investigate the effects of an intramolecular disulfide bond on
      protein structure and ligand binding dynamics in myoglobin, we prepared a mutant
      myoglobin having a disulfide bond at the EF corner by introducing two cysteine at
      the position of Ile 75 and Glu 85. On the basis of the spectral features of the
      mutant, the formation of the disulfide bond only affected minor structural
      deviations of the heme environmental structure in the carbonmonoxy form, whereas
      more substantial structural alterations were induced in the deoxygenated form.
      Laser photolysis experiments for carbon monoxide rebinding clearly showed that
      the artificial S-S bond accelerates the bimolecular rebinding rate from 1.0 to
      1.8 microM-1 s-1 and increases the geminate yield from 0.072 to 0.092. The ligand
      migration rate from the solvent to the heme pocket and the bond formation rate
      from the heme pocket to the heme iron also increased. The free energy diagram for
      the mutants indicates that the energy barrier for the bond formation was raised
      as well as that for the ligand migration by introduction of the disulfide bond.
      However, the effects of the disulfide linkage at the EF corner on the kinetic
      parameter is much smaller than those of the amino acid substitutions located in
      the heme cavity. We can conclude that the perturbation of the protein
      fluctuations by formation of the disulfide bond would be localized at the
      mutation site or the contributions from other regions and motions might be more
      important for the ligand binding dynamics.

PMID- 9003185
TI  - Is the structure of the N-domain of phosphoglycerate kinase affected by isolation
      from the intact molecule?
AB  - The structural integrity of the isolated N-domain (residues 1-174) of Bacillus
      stearothermophilus 3-phosphoglycerate kinase (PGK) has been investigated using
      heteronuclear NMR spectroscopy. Analysis of 13C chemical shifts, amide
      protection, and comparison of observed and expected sequential NOE intensities
      calculated from the crystal structure of the domain in the intact protein
      indicate that the secondary structure of the isolated domain is unchanged from
      that found in the intact molecule. Markedly shifted 1H resonances, amide
      protection, and long-range NOEs indicate that the tertiary structure is similarly
      unaffected. These results are confirmed by an excellent agreement (standard
      deviation 0.28 ppm) between observed H alpha chemical shifts and those calculated
      from the high-resolution (1.6 A) crystal structure of intact PGK [Davies et al.
      (1994) Acta Crystallogr. D50, 202-209]. The only region perturbed by loss of
      interactions with the C-domain is a small portion of the substrate-binding site
      (residues 148-152) whose amide protons are poorly protected from solvent. These
      results provide a structural basis for the analysis of the folding of the domains
      of PGK as isolated units and within the intact molecule [Parker et al. (1996)
      Biochemistry (in press)] and contrast with the notion that the native tertiary
      fold of the N-domain of PGK requires the whole polypeptide chain, including the
      entire C-domain [Mas et al. (1995) Biochemistry 34, 7931-7940]. Assignments of
      backbone 13C, 15N, HN, and H alpha resonances are provided.

PMID- 9003186
TI  - Mutagenesis of the histidine ligand in human lactoferrin: iron binding properties
      and crystal structure of the histidine-253-->methionine mutant.
AB  - The contribution of the conserved His ligand to iron binding in transferrins has
      been addressed by site-directed mutagenesis and X-ray crystallographic analysis.
      His 253 in the N-terminal half-molecule of human lactoferrin, LfN (residues 1
      333), has been changed to Gly, Ala, Pro, Thr, Leu, Phe, Met, Tyr, Glu, Gln, and
      Cys by oligonucleotide-directed mutagenesis. The proteins have been expressed in
      baby hamster kidney cells, at high levels, and purified. The results show that
      the His ligand is essential for the stability of the iron binding site. All of
      the substitutions destabilized iron binding irrespective of whether the
      replacements were potential iron ligands or not. Iron was lost below pH
      approximately 6 for the Cys, Glu, and Tyr mutants and below pH 7 or higher for
      the others, compared with pH 5.0 for LfN. The destabilization is attributed to
      both steric and electronic effects. The importance of electronic effects has been
      shown by the crystal structure of the H253M mutant, which has been determined at
      an effective resolution of 2.5 A and refined to a final R factor of 0.173. The
      iron atom is changed from six-coordinate to five-coordinate; the Met 253 side
      chain is not bound to iron even though there appears to be no steric barrier.
      This is attributed to the poorer affinity of the thioether ligand for Fe(III)
      compared with imidazole nitrogen. The decreased stability of the iron binding is
      attributed solely to the loss of the His ligand as the protein conformation and
      interdomain interactions are unchanged.

PMID- 9003187
TI  - Activation of phosphatidylinositol-specific phospholipase C toward inositol 1,2
      (cyclic)-phosphate.
AB  - Phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus
      thuringiensis catalyzes the hydrolysis of phosphatidylinositol (PI) in discrete
      steps: (i) an intramolecular phosphotransferase reaction to form inositol 1,2
      (cyclic)-phosphate (cIP), followed by (ii) a cyclic phosphodiesterase activity
      that converts cIP to inositol 1-phosphate. Water-soluble cIP was used as the
      substrate to study the cyclic phosphodiesterase activity and interfacial behavior
      of PI-PLC. Different detergent micelles and phospholipid vesicles were used to
      examine if "interfacial activation" of the enzyme could occur toward a soluble
      substrate. Almost all detergents examined activated the enzyme at least 2-fold,
      with PC species yielding the largest increases in PI-PLC specific activity.
      Kinetic parameters were measured in the absence and presence of several
      representative detergents (e.g., Triton X-100 and diheptanoylphosphatidylcholine
      (diC7PC)). Gel filtration experiments showed that, under these conditions, the
      cIP did not partition to any measurable extent with these detergent micelles. The
      concentration at which half the maximum activation was observed occurred near the
      detergent CMC. Both Km and Vmax were altered by the presence of a surface: Km
      decreased to different degrees depending on the detergent, while Vmax increased
      substantially. The Km for cIP was 90 mM without detergent and decreased to 29 mM
      with diC7PC micelles added; Vmax increased almost 7-fold in the presence of
      diC7PC micelles. The enzyme efficiency (Vmax/Km) in the presence of diC7PC
      increased more than 21-fold, but it was still 20-fold lower than initial
      phosphotransferase activity for monomeric dihexanoylphosphatidylinositol. The
      poor efficiency of the cyclic phosphodiesterase activity is largely due to
      substrate binding affinity. The dependence of rate on substrate concentration
      exhibits cooperative behavior, especially without detergent. This cooperativity
      is discussed in terms of protein aggregation and ligand binding sites on the
      enzyme.

PMID- 9003188
TI  - Stereocontrolled syntheses of water-soluble inhibitors of phosphatidylinositol
      specific phospholipase C: inhibition enhanced by an interface.
AB  - Three inositol 1,2-(cyclic)-phosphate analogs, inositol cyclic phosphonates with
      different stereochemistry at the C-2 position of the inositol ring, have been
      synthesized as water-soluble inhibitors of phosphatidylinositol-specific
      phospholipase C (PI-PLC). Their inhibition of both phosphotransferase and cyclic
      phosphodiesterase activities has been studied in the absence and presence of an
      interface. Key results include the following. (i) Only the analog with the same
      stereochemistry at the C-2 position of the inositol ring as the natural
      substrate, myo-inositol 1,2-(cyclic)-phosphate (cIP), exhibits effective
      inhibition of PI-PLC. (ii) The inhibition of the PI-PLC cyclic phosphodiesterase
      activity by this cIP analog is enhanced by the presence of an interface (Triton X
      100 or diC7PC micelles). This is the first observation of detergent enhancing the
      effectiveness of a water-soluble inhibitor competing with a water-soluble
      substrate. (iii) For the cyclic phosphodiesterase activity measured in the
      presence of 8 mM of the best (e.g., most activating) interface, diC7PC, myo
      inositol 1,2-(cyclic)-2-methylenephosphonate (cICH2P) was shown to be a
      competitive inhibitor with a Ki of 12.3 mM. (iv) The IC50 obtained for the same
      compound inhibiting the PI-PLC hydrolysis of PI dispersed in DiC7PC micelles was
      consistent with a Ki approximately 10 mM for the phosphotransferase activity. The
      similarity of Ki for both PI and cIP processing by PI-PLC suggests both reactions
      occur at the same site on the enzyme.

PMID- 9003189
TI  - Tryptophan residues in caldesmon are major determinants for calmodulin binding.
AB  - Calmodulin has been shown to interact with the COOH-terminal domain of gizzard h
      caldesmon at three sites, A (residues 658-666), B (residues 687-695), and B'
      (residues 717-725), each of which contains a Trp residue [Zhan et al. (1991) J.
      Biol. Chem. 266, 21810-21814; Marston et al. (1994) J. Biol. Chem. 296, 8134
      8139; Mezgueldi et al. (1994) J. Biol. Chem. 269, 12824-12832]. To determine the
      contribution of each of the three Trp residues in the calmodulin-caldesmon
      interaction, we have mutated the Trp residues to Ala in the COOH-terminal domain
      of fibroblast caldesmon (CaD39) and studied the effects on calmodulin binding by
      fluorescence measurements and using immobilized calmodulin. Wild-type CaD39 binds
      with a Kd of 0.13 x 10(-6) M and a stoichiometry of 1 mol of calmodulin per mol
      of caldesmon. Replacing Trp 659 at site A or Trp 692 at site B to Ala reduces
      binding by 22- and 31-fold (Kd = 2.9 x 10(-6) and 4.0 x 10(-6) M), respectively,
      and destabilizes the CaD39-calmodulin complex by 1.75 and 1.94 kcal mol-1,
      respectively. Mutation of both Trp 659 and Trp 692 to Ala further reduces binding
      with a Kd of 6.1 x 10(-6) M and destabilizes the complex by 2.17 kcal mol-1. On
      the other hand, mutation of Trp 722 at site B' to Ala causes a much smaller
      decrease in affinity (Kd = 0.6 x 10(-6) M) and results in a destabilization
      energy of 0.87 kcal mol-1. To investigate the relative importance of the amino
      acid residues near each Trp residue in the caldesmon-calmodulin interaction,
      deletion mutants were constructed lacking site A, site B, and site A + B.
      Although deletion of site A decreases binding of CaD39 to calmodulin by 13-fold
      (Kd = 1.7 x 10(-6) M), it results in tighter binding than mutation of Trp 659 to
      Ala at this site, suggesting that the residues neighboring Trp 659 may contribute
      negatively to the interaction. Deletion of site B causes a similar reduction in
      binding (Kd = 4.1 x 10(-6) M) as observed for replacing Trp 692 to Ala at this
      site, indicating that Trp 692 is the major, if not the only, binding determinant
      at site B. Deletion of both site A and site B drastically reduces binding by 62
      fold. Taken together, these results suggest that Trp 659 and Trp 692 are the
      major determinants in the caldesmon-calmodulin interaction and that Trp 722 in
      site B' plays a minor role.

PMID- 9003190
TI  - Cooperativity in oxidations catalyzed by cytochrome P450 3A4.
AB  - Cytochrome P450 (P450) 3A4 is the most abundant human P450 and oxidizes a
      diversity of substrates, including various drugs, steroids, carcinogens, and
      macrolide natural products. In some reactions, positive cooperativity has been
      reported in microsomal studies. Flavonoids, e.g., 7,8-benzoflavone (alpha
      naphthoflavone, alpha NF), have been shown to stimulate some reactions but not
      others. In systems containing purified recombinant bacterial P450 3A4, positive
      cooperativity was seen in oxidations of several substrates, including
      testosterone, 17 beta-estradiol, amitriptyline, and most notably aflatoxin (AF)
      B1. With these and other reactions, alpha NF typically reduced cooperativity
      (i.e., the n value in a Hill plot) while either stimulating or inhibiting
      reactions. With the substrate AFB1, alpha NF both stimulated 8,9-epoxidation and
      inhibited 3 alpha-hydroxylation. The same patterns were seen with AFB1 in a fused
      P450 3A4-NADPH-P450 reductase protein. alpha NF did not alter patterns of
      activity plotted as a function of NADPH-P450 reductase concentration in systems
      containing the individual proteins. The patterns of AFB1 oxidation to the two
      products were modified considerably in systems in which NADPH-P450 reductase was
      replaced with a flavodoxin or ferredoxin system, iodosylbenzene, or cumene
      hydroperoxide. AFB2, which differs from AFB1 only in the presence of a saturated
      8,9-bond, was not oxidized by P450 3A4 but could inhibit AFB1 oxidation. These
      and other results are considered in the context of several possible models. The
      results support a model in which an allosteric site is involved, although the
      proximity of this putative site to the catalytic site cannot be ascertained as of
      yet. In order to explain the differential effects of alpha NF and reduction
      systems on the two oxidations of AFB1, a model is presented in which binding of
      substrate in a particular conformation can facilitate oxygen activation to
      enhance catalysis.

PMID- 9003192
TI  - Binding affinity and specificity of Escherichia coli RNase H1: impact on the
      kinetics of catalysis of antisense oligonucleotide-RNA hybrids.
AB  - In this study we report for the first time the binding affinity of RNase H1 for
      oligonucleotide duplexes. We used a previously described 17-mer antisense
      sequence [Monia, B. P., Johnston, J. F., Ecker, D. J., Zounes, M. A., Lima, W.
      F., & Freier, S. M. (1992) J. Biol. Chem. 267, 19954-19962] hybridized to a
      complementary oligoribonucleotide to evaluate both the binding affinity and the
      catalytic rate of RNase H1. The dissociation constants (Kd) of RNase H1 for the
      various substrates tested were determined by inhibition analysis using chemically
      modified noncleavable oligonucleotide heteroduplexes. Catalytic rates were
      determined using heteroduplex substrates containing chimeric antisense
      oligonucleotides composed of a five-base deoxynucleotide sequence flanked on
      either side by chemically modified nucleotides. We find that the enzyme
      preferentially binds A-form duplexes: RNase H bound A-form duplexes (RNA:RNA and
      DNA:RNA) approximately 60-fold tighter than B-form duplexes (DNA:DNA) and
      approximately 300-fold tighter than single-strand oligonucleotides. The enzyme
      exhibited equal affinity for both the wild type (RNA:DNA) oligonucleotide
      substrate and heteroduplexes containing various 2'-sugar modifications, while the
      cleavage rates for these chemically modified substrates were without exception
      slower than for the wild type substrate. The introduction of a single positively
      charged 2'-propoxyamine modification into the chimeric antisense oligonucleotide
      portion of the heteroduplex substrate resulted in both decreased binding affinity
      and a slower rate of catalysis by RNase H. The cleavage rates for heteroduplexes
      containing single-base mismatch sequences within the chimeric oligonucleotide
      portion varied depending on the position of the mismatch but had no effect on the
      binding affinity of the enzyme. These results offer further insights into the
      physical binding properties of the RNase H-substrate interaction as well as the
      design of effective antisense oligonucleotides.

PMID- 9003191
TI  - Flexibility of liver alcohol dehydrogenase in stereoselective binding of 3
      butylthiolane 1-oxides.
AB  - Thiolane 1-oxides are analogs of the carbonyl substrates that bind to the alcohol
      dehydrogenase-NADH complex and are potent uncompetitive inhibitors against
      alcohol [Chadha, V. K., et al. (1985) J. Med. Chem. 28, 36-40]. The four
      stereoisomers of 3-butylthiolane 1-oxide (BTO) were separated by chiral phase
      chromatography. CD and 1H-NMR spectra identified the enantiomeric pairs. 1H-NMR
      chemical shifts were assigned on the basis of COSY spectra of both
      diastereoisomers and confirmed by HMQC spectra. Coupling constants were
      determined through one-dimensional decoupling experiments. NMR with chiral shift
      reagents, Eu(hfc)3 [europium tris [3-[(heptafluoropropyl)hydroxymethylene]-(+)
      camphorate]] or (R)-(-)-N-(3,5-dinitrobenzoyl)-alpha-methylbenzylamine,
      determined that the most inhibitory isomer is either 1S,3R or 1R,3S. The chemical
      shifts of protons in the thiolane 1-oxide ring were influenced by the whole
      structure and were not correlated with the computed Mulliken charges. X-ray
      crystallography at 2.1 and 1.66 A resolution of the ternary enzyme complexes with
      NADH demonstrated that the absolute configuration of the most inhibitory (Kii =
      0.31 microM) stereoisomer is 1S,3R and the next best inhibitor (Kii = 0.73
      microM) is 1S,3S. The thiolane 1-oxide rings bind in the same position, in the
      substrate binding site, but the geometry of the complexes suggests that the
      sulfoxides are not transition state analogs. Significantly, the butyl groups of
      the two isomers are accommodated differently by flexible amino acid side chains
      adopting alternative rotameric conformations.

PMID- 9003193
TI  - Conformation of formacetal and 3'-thioformacetal nucleotide linkers and stability
      of their antisense RNA.DNA hybrid duplexes.
AB  - This study focuses on the characterization of the stability and conformation of
      the antisense oligodeoxyribonucleotides, d[CGCGTT x TTGCGC] [x = phosphodiester (
      O-P(O)2-O-), formacetal (FMA, -O-CH2-O-), or 3'-thioformacetal linkage (TFMA, -S
      CH2-O-)], in DNA.DNA and RNA.DNA duplexes (designated DI-III and RI-III,
      respectively). NMR analysis of two RNA.DNA hybrid duplexes containing a single
      FMA (the RII duplex) or 3'-TFMA (the RIII duplex) modification has been carried
      out. The conformations of these duplexes are compared with that of the unmodified
      hybrid duplex RI and with those of the DI-III duplexes. These analyses and
      comparisons indicate that the residue containing a 3'-FMA linker has a preference
      for the C2'-endo sugar pucker and adopts a canonical backbone conformation. In
      contrast, the residue containing a 3'-TFMA linker has a much increased preference
      for the C3'-endo sugar pucker and adopts different backbone conformations in the
      DNA.DNA and RNA.DNA duplexes. UV and NMR melting studies of the six duplexes
      demonstrate that the DNA.DNA duplexes are more stable than the corresponding
      RNA.DNA hybrid duplexes and that both FMA and 3'-TFMA destabilize the duplex. The
      3'-TFMA modified duplex is less stable than the FMA duplex in the context of
      DNA.DNA recognition and is slightly more stable than the FMA hybrid duplex in the
      context of RNA.DNA recognition. These results suggest a correlation between the
      conformational preference of backbone modifications and the stability of
      antisense duplexes. The implications of these studies for optimized incorporation
      of FMA and 3'-TFMA linkers into oligonucleotides and for better design of
      antisense oligonucleotide analogs are discussed.

PMID- 9003194
TI  - Progress curve analysis of the kinetics with which blood coagulation factor XIa
      is inhibited by protease nexin-2.
AB  - Protease nexin-2 (PN-2), a soluble form of amyloid beta-protein precursor (APP)
      containing a Kunin protease inhibitor domain, has been shown to be a potent,
      reversible and competitive inhibitor of blood coagulation factor XIa (FXIa). We
      have analyzed progress curves of the hydrolysis of a sensitive fluorogenic
      substrate by FXIa in the presence of PN-2 to ascertain the kinetic rate constants
      governing the inhibition of FXIa by PN-2. The mechanism of this inhibition is
      best described as a slow equilibration between the free enzyme and inhibitor
      directly, without prior formation of a loosely-associated complex. The
      association rate constant (kon) and the dissociation rate constant (koff) were
      found to be 2.1 +/- 0.2 x 10(6) M-1 s-1 and 8.5 +/- 0.8 x 10(-4) s-1,
      respectively (n = 23). The inhibition constant calculated from these parameters
      (Ki) is 400 pM, in good agreement with previous reports. High molecular weight
      kininogen (HK) and Zn2+ ions exert opposite effects on the inhibition of FXIa by
      PN-2. HK protects FXIa from inactivation in a dose dependent and saturable manner
      (EC50 = 61 nM) whereas Zn2+ augments the ability of PN-2 to inhibit FXIa. When
      both Zn2+ ions and HK are present, only the accessory effect of Zn2+ is observed.
      PN-2 is known to be an abundant platelet alpha-granule protein (Van Nostrand et
      al., 1990a; Smith & Broze, 1992). We conducted sensitive measurements of FXIa
      activity in the presence of human platelets before and after their being
      activated with the thrombin receptor agonist peptide, SFLLRN-amide. We found that
      platelet activation, and ostensibly the release of PN-2, limits the lifetime of
      FXIa activity within the locus of activated platelets. As in the purified system,
      HK protects FXIa from inactivation and Zn2+ increases the inactivation of FXIa.
      However, when HK and Zn2+ are both present, it is the protective effect of HK
      which predominates and prolongs the lifetime of FXIa after platelet activation.

PMID- 9003195
TI  - Outer leaflet-packing defects promote poly(ethylene glycol)-mediated fusion of
      large unilamellar vesicles.
AB  - Poly(ethylene glycol)-induced fusion of two different vesicle systems has been
      examined: dipalmitoylphosphatidylcholine (DPPC) large unilamellar vesicles (LUV)
      and cardiolipin (CL)/dioleoylphosphatidylcholine (DOPC) (1:10) LUVs. A slight
      perturbation was established in the outer leaflets of DPPC LUVs by hydrolyzing
      0.8% of the outer leaflet lipid with phospholipase A2 to produce
      lysophosphatidylcholine and palmitate which were then removed by bovine serum
      albumin. Similarly, 5 mM Ca2+ was added to the external compartment of CL/DOPC
      LUVs to alter the shape of the CL molecule and thereby create a perturbation in
      the outer leaflet packing of these vesicles. Contents mixing assays showed that
      both vesicle systems fused only when the outer leaflets of both contacting
      vesicles were perturbed as described. Two fluorescent probes (C6-NBD-PC and TMA
      DPH) were used to detect changes in outer leaflet molecular packing between
      nonfusing and fusing systems. The steady-state fluorescence intensity of C6-NBD
      PC added externally to either fusing system was enhanced relative to that of
      nonfusing vesicles. Phase-resolved measurements of probe lifetime showed that
      this was due mainly to enhanced partitioning of probe from a micellar state into
      fusing versus nonfusing membranes. Similarly, TMA-DPH was found to undergo more
      rapid motion when incorporated into fusing as opposed to nonfusing vesicles. The
      effects of deuterium exchange on probe lifetime also indicated that C6-NBD-PC and
      TMA-DPH penetrated more deeply into fusing than into nonfusing membranes. These
      results suggest that the fusogenic perturbations produced in these two very
      different lipid systems took the form of altered outer leaflet packing. We
      conclude that, for the two model lipid bilayers examined, small perturbations in
      lipid packing within contacting bilayer leaflets are necessary and probably
      sufficient to promote membrane fusion.

PMID- 9003196
TI  - Dinuclear center of ferritin: studies of iron binding and oxidation show
      differences in the two iron sites.
AB  - The ferroxidase activity of human ferritin has previously been associated with a
      diiron site situated centrally within the four-helix bundle of H-type chains
      (HuHF). However, direct information about the site of Fe(II) binding has been
      lacking, and events between Fe(II) binding and its oxidation have not previously
      been studied. A sequential stopped-flow assay has now been developed to enable
      the dissection of binding and oxidation. It depends on the ability of 1,10
      phenanthroline to complex protein-bound Fe(II) and to distinguish it from the
      more immediately available free Fe(II). This approach, aided by the use of site
      directed variants, indicates that in HuHF and the non-heme ferritin of
      Escherichia coli the first 48 Fe(II) atoms/molecule added are bound and oxidized
      at the dinuclear centers. At a constant iron concentration, the rate of Fe(II)
      oxidation was maximal for additions of 2 Fe(II) atoms/subunit, consistent with a
      two-electron oxidation of the Fe(II) pair. Although, at low Fe(II)/protein
      ratios, no cooperativity in Fe(II) binding was observed; a preferred order of
      binding was deduced [Fe(II) binding first at site A and then at site B]. Binding
      of Fe(II) at both sites was essential for fast oxidation. Modification of site A
      ligands resulted in slow iron binding and slow oxidation. Modification of site B
      did not prevent Fe(II) binding at site A but greatly reduced its oxidation rate.
      These differences may mean that dioxygen is initially bound to Fe(II) at site B.

PMID- 9003197
TI  - Carboxy-terminal regions of the sarcoplasmic/endoplasmic reticulum Ca(2+)- and
      the Na+/K(+)-ATPases control their K+ sensitivity.
AB  - The Na+,K(+)-ATPase and the sarcoplasmic/endoplasmic reticulum Ca(2+)-(SERCA-)
      ATPase belong to a family of P-type ATPases that undergo a cycle of
      conformational changes between the phosphorylated and dephosphorylated stages in
      an ion-specific manner. The ouabain-inhibitable Na+,K(+)-ATPase activity requires
      Na+ and K+. On the other hand, the Ca(2+)-dependent and thapsigargin-inhibitable
      activity of the SERCA-ATPase does not depend upon Na+ and K+ for its basal
      activity. However, the SERCA-ATPase and Ca(2+)-transport activities can be
      further activated either by K+ in a two-step fashion with high (ED50
      approximately 20 mM) and low affinity (ED50 approximately 70 mM) or by Na+ in a
      one-step fashion with an ED50 value of approximately 50 mM. A chimera, in which
      the carboxy-terminal region (Leu861-COOH) of the Na+,K(+)-ATPase alpha 1 subunit
      replaced the corresponding region (Ser830-COOH) of the SERCA1-ATPase, lacked the
      low-affinity K+ activation of the SERCA-ATPase but displayed a higher-affinity
      (ED50 < 10 mM) activation by K+, similar to that of the Na+,K(+)-ATPase, whereas
      activation by Na+ was not affected. The replacement of the large cytosolic loop
      (Gly354-Lys712) and the amino-terminal regions (Met1-Asp162) of the SERCA1-ATPase
      with the corresponding portions of the Na+,K(+)-ATPase alpha 1 subunit did not
      affect the sensitivity of the SERCA-ATPase activity to K+. Thus, the carboxy
      terminal regions of both the SERCA1 and the Na+,K(+)-ATPase alpha 1 subunit are
      critical for K+ sensitivity. Analysis of additional (Ca2+/Na+,K+)-ATPase chimeras
      demonstrated that the carboxy-terminal 102 amino acids (Phe920-Tyr1021) of the
      Na+/K(+)-ATPase alpha 1 subunit are sufficient to shift the K+ affinity for
      activation of the SERCA-ATPase without the beta subunit. No change in the two
      step activation of SERCA-ATPase by K+ was seen when residues Thr871-Thr898 of the
      SERCA1-ATPase were replaced with residues Asn894-Ala919 of the Na+,K(+)-ATPase
      alpha 1 subunit, a region known to bind the Na+,K(+)-ATPase beta subunit [Lemas,
      M. V., et al. (1994) J. Biol. Chem. 269, 8255-8259]. Thus, the Na+,K(+)-ATPase
      subunit-assembly domain and the K(+)-sensitive region are distinct within the
      carboxy-terminal 161 amino acids of the Na+,K(+)-ATPase.

PMID- 9003199
TI  - Privacy in the electronic age.

PMID- 9003198
TI  - Identification of the histidyl residue obligatory for the catalytic activity of
      the human H+/peptide cotransporters PEPT1 and PEPT2.
AB  - Histidyl residues are known to be essential for the catalytic function of the
      H(+)-coupled peptide transporters expressed in the intestine and the kidney, most
      likely participating in the binding and translocation of H+. Three histidyl
      residues are conserved among the intestinal and renal peptide transporters (PEPT1
      and PEPT2, respectively) from different animal species. In hPEPT1, these residues
      are His-57, His-121, and His-260. The corresponding residues in hPEPT2 are His
      87, His-142, and His-278. We have individually mutated each of these histidyl
      residues in hPEPT1 and in hPEPT2 and compared the catalytic function of the
      mutants with that of their respective wild type transporters by expressing the
      transporters in Xenopus laevis oocytes and also in HeLa cells. His-57 in hPEPT1
      and His-87 in hPEPT2 were found to be absolutely essential for catalytic activity
      because the corresponding mutants had no detectable peptide transport activity.
      His-121 in hPEPT1 is not essential since mutation of this residue did not impair
      transport function. His-142 in hPEPT2 was found to play a significant role in the
      maintenance of transport function but was not found to be obligatory because the
      mutant had appreciable transport activity. The obligatory histidyl residue (His
      57 in hPEPT1 and His-87 in hPEPT2) is located in an almost identical topological
      position in both transporters, near the extracellular surface of the second
      putative transmembrane domain. The second conserved histidyl residue is located
      in the fourth putative transmembrane domain in hPEPT1 as well as in hPEPT2. The
      third conserved histidyl residue is present in the cytoplasmic loop between the
      transmembrane domains 6 and 7 and is unlikely to play any significant role in the
      binding and translocation of H+ and this was supported by the findings that
      mutation of this histidyl residue in hPEPT1 did not interfere with transport
      function. The loss of transport function of hPEPT1 and hPEPT2, when His-57 in
      hPEPT1 and His-87 in hPEPT2 were mutated, was not due to alterations in protein
      expression because the expression levels of these mutants were similar to those
      of the respective wild type transporters in HeLa cells as assessed by immunoblot
      analysis. Confocal analysis of immunofluorescence in X. laevis oocytes expressing
      the wild type and the three histidine mutants of hPEPT1 showed that the
      transporter protein is expressed exclusively in the plasma membrane and that the
      level of expression is comparable among the wild type and the three mutants.
      These site-directed mutagenesis studies clearly show that His-57 in hPEPT1 and
      His-87 in hPEPT2 are the most critical histidyl residues necessary for the
      catalytic function of these transporters.

PMID- 9003200
TI  - Confetti-like spots on the legs and arms.

PMID- 9003202
TI  - Preventive maintenance for the midlife patient.

PMID- 9003201
TI  - Sleep problems in older adults: putting myths to bed.
AB  - Many people believe that older adults need less sleep. However, it is not the
      need for sleep but the ability to sleep that diminishes with age. Older adults
      are objectively sleepier in the day, indicating they are not getting enough sleep
      at night. Their sleep is disrupted by circadian rhythm changes, disorders such as
      sleep disordered breathing (apnea) and periodic limb movements in sleep (PLMS),
      medical illness, psychiatric illness, medication use, and poor sleep habits. The
      physician can address each of these causes, thereby improving the night-time
      sleep and daytime functioning of the older adult.

PMID- 9003203
TI  - Weight control and nutrition: knowing when to intervene.
AB  - The average weight of American adults is increasing, despite vast sums being
      spent on attempts at weight loss. Above-average weight in midlife is associated
      with increased morbidity and mortality as patients age. Nonetheless, there is
      confusion about what are "desirable" weight levels. Commonly-used actuarial
      tables do not account for the modest, normal weight gains seen at midlife;
      therefore, age-adjusted tables are recommended. Treatment of obesity, one of the
      most common malnutrition disorders, is difficult, requires a "chronic disease"
      approach, and should be considered in the context of other risks to health.

PMID- 9003204
TI  - Interleukin-4 and its receptor: essential mediators of the allergic response.

PMID- 9003205
TI  - Childhood antecedents of allergic sensitization in young British adults.
AB  - OBJECTIVE: This study was designed to investigate whether associations of self
      reported hay fever with sibship size, birth order, infant feeding, and childhood
      socioeconomic status reflect variations in sensitization to common aeroallergens.
      METHODS: One thousand three hundred sixty-nine persons born throughout Britain in
      1958 were followed up to age 34 to 35 years. The cohort included 1050 subjects
      with a history of asthma, wheezy bronchitis, wheezing, or pneumonia and 319 with
      no history of wheezing illness at ages 7, 11, 16, 23, or 33 years. Skin prick
      tests with extracts of mixed grass pollen, house dust mite (Der p 1), and cat fur
      were performed; and wheal diameters were measured. RESULTS: The prevalence of
      positive skin test results (> or = 3 mm wheal) was independently related (p <
      0.01) to male sex, reduced numbers of older siblings (but not younger siblings),
      and higher socioeconomic status in childhood. Current cigarette smoking and
      maternal smoking during pregnancy were independently associated (p < 0.01) with a
      reduced prevalence of skin prick test positivity. No significant independent
      effects (p > 0.10) were found for adult social class, maternal age, birth weight,
      gestation, breast feeding, preschool nursery attendance, urban birthplace, or gas
      stove exposure. CONCLUSION: Factors related to small families and relative
      affluence in childhood promote atopic sensitization to a variety of aeroallergens
      in later life. These observations are consistent with the suggestion that early
      infection may protect against subsequent allergic disease.

PMID- 9003206
TI  - A twelve-week comparison of salmeterol and salbutamol in the treatment of mild-to
      moderate asthma: a Canadian multicenter study.
AB  - BACKGROUND: A long-acting inhaled bronchodilator that is both well tolerated and
      effective could allow for improved control of both daytime and nighttime symptoms
      in patients with asthma who use frequent as-needed short-acting bronchodilators
      despite antiinflammatory treatment. OBJECTIVE AND METHODS: We compared the
      efficacy and safety of inhaled salmeterol, 50 micrograms twice daily, with
      inhaled salbutamol, 200 micrograms four times daily, delivered through a metered
      dose inhaler for 3 months in a multicenter, randomized, double-blind, parallel
      group study of 228 patients (aged 12 to 76 years) with mild-to-moderate asthma.
      RESULTS: A single morning dose of salmeterol produced improvement in FEV1 that
      was significantly greater (p < or = 0.012) than that produced by two doses of
      salbutamol (taken 6 hours apart) when patients were assessed 3 to 6 hours and 10
      to 12 hours after the dose. This greater bronchodilation was present on day 1 of
      the study and after 4, 8, and 12 weeks of regular treatment. Over the 12 weeks,
      compared with salbutamol, salmeterol treatment was associated with a greater mean
      improvement in morning peak expiratory flow (35 L/min vs -3 L/min, p < 0.001), a
      higher percentage of days with no symptoms (29% vs 15%; p = 0.012), and a higher
      percentage of nights with no awakenings (14% vs -1%; p < 0.001). Adverse events
      were similar for both treatments. CONCLUSIONS: In this study salmeterol, 50
      micrograms twice daily, was well tolerated and more effective than salbutamol,
      200 micrograms four times daily, in improving symptoms and lung function in
      patients with mild-to-moderate asthma.

PMID- 9003207
TI  - A cost of illness study of allergic rhinitis in the United States.
AB  - BACKGROUND: Allergic rhinitis is a common condition, but the burden of this
      condition on the national economy is not well understood. OBJECTIVE: The purpose
      of this study was to estimate the national direct and indirect costs of allergic
      rhinitis. METHODS: Data from the National Medical Expenditure Survey were used to
      provide estimates of resource utilization, medical expenditures, and lost
      productivity. With the complex survey design, variance estimates were used to
      construct confidence intervals for cost estimates of resource utilization and
      lost productivity. RESULTS: It is estimated that approximately 39 million persons
      in the United States experienced allergic rhinitis in 1987. However, only 12.3%
      (4.8 million) sought medical treatment for allergic rhinitis. The total estimated
      cost of the condition, in 1994 dollars, was $1.23 billion (95% confidence
      interval, $846 million to $1.62 billion). Direct medical expenses accounted for
      94% of total costs. Allergic rhinitis results in approximately 811,000 missed
      workdays, 824,000 missed school days, and 4,230,000 reduced activity days.
      CONCLUSION: Allergic rhinitis clearly creates a burden in terms of the number of
      persons affected, total expenditures, and lost productivity. It also appears that
      a relatively large proportion of persons with allergic rhinitis were not seeking
      medical treatment.

PMID- 9003208
TI  - Differential efficacy of lymphocyte- and monocyte-selective pretreatment with a
      type 4 phosphodiesterase inhibitor on antigen-driven proliferation and cytokine
      gene expression.
AB  - Elevations of intracellular cyclic AMP, achieved with the use of
      phosphodiesterase (PDE) inhibitors, cause functional downregulation of most
      inflammatory cells. Rolipram, an inhibitor selective for the PDE4 isozyme, can
      markedly downregulate antigen-driven proliferation and cytokine gene expression
      of unfractionated human peripheral blood mononuclear cells. However, it is
      unclear whether PDE4 inhibitors in a mixed-cell system exert their
      immunosuppressive effect on the lymphocyte or on the monocyte fraction. We have
      used an adherence-based protocol for separating peripheral blood mononuclear
      cells, isolated from atopic individuals, into lymphocyte and monocyte fractions
      and have selectively treated these populations with rolipram prior to
      reconstituting the cell cultures to their original lymphocyte/monocyte
      proportions. Cellular responses to both ragweed and tetanus toxoid were analyzed
      for both proliferation and gene expression of proinflammatory cytokines. A dose
      dependent downregulation of ragweed- and tetanus toxoid-driven proliferative
      responses was achieved by pretreatment of lymphocytes from peripheral blood with
      rolipram. This downregulation was significantly greater than that achieved with
      pretreatment of monocytes. Pretreatment of both populations failed to show
      synergistic downregulation of proliferation. Lymphocyte pretreatment with
      rolipram also resulted in marked downregulation of gene expression for IL-4, IL
      5, and interferon-gamma compared to monocyte pretreatment in both ragweed- and
      tetanus toxoid-driven systems. Interestingly, monocyte pretreatment in these
      systems resulted in significant downregulation of IL-2 gene expression compared
      to lymphocyte pretreatment. Flow cytometric analysis failed to show alterations
      in any of a panel of surface activation and signal transducing molecules by
      rolipram treatment with or without antigen stimulation. We conclude that, in a
      mixed cell system, PDE4 inhibitors downregulate antigen-driven proliferation and
      gene expression of proinflammatory cytokines predominantly through their effects
      on lymphocytes rather than monocytes.

PMID- 9003209
TI  - Failure of aged rats to accumulate eosinophils in allergic inflammation of the
      airway.
AB  - To investigate the effect of aging on the allergic airway response, we examined
      the bronchoconstrictive responses and cellular inflammatory changes in a rat
      model of bronchial asthma by evaluating young and old animals. Two different age
      groups of Brown-Norway rats, actively sensitized by injection of ovalbumin into
      the foot pads, were used: 7 to 8 weeks old (young group) and 100 to 120 weeks old
      (aged group). Both the aged and young rats produced on ovalbumin-specific IgE
      antibody and exhibited an immediate asthmatic response after exposure to
      ovalbumin, but the degree of specific IgE antibody was significantly higher in
      young rats. The young group showed a marked increase in the number of eosinophils
      and neutrophils in bronchoalveolar lavage fluid 2 days after exposure to
      ovalbumin, whereas no eosinophilia was seen in the aged group. To evaluate the
      mechanism of the decreased accumulation of eosinophils in aged rats, cells from
      popliteal lymph nodes from ovalbumin-sensitized rats were incubated with
      ovalbumin for 48 hours. Although eosinophil chemotactic activity, determined by a
      modified Boyden chamber method, was present in the supernatant of cultured lymph
      node cells from young rats, it was absent from those of aged rats. In vivo
      administration of anti-IL-5 monoclonal antibody revealed that one of the factors
      of eosinophil chemotactic activity was IL-5. Lymph node cells from aged rats
      tended to produce greater amounts of interferon-gamma than did those from young
      animals. Findings indicate that aged rats have a defect in eosinophil
      accumulation in sites exposed to antigen, probably because of an age-dependent
      alteration in T cells.

PMID- 9003210
TI  - Restoration of the mucociliary clearance of the maxillary sinus after endoscopic
      sinus surgery.
AB  - BACKGROUND: Whether endoscopic sinus surgery (ESS) restores the mucociliary
      clearance of the maxillary sinus needs further evaluation. METHODS: We evaluated
      the mucociliary clearance of the maxillary sinus by using a radionuclide
      technique in 12 patients with chronic sinusitis (sinusitis group) and in six
      patients who had undergone ESS 6 to 14 months after the surgery (post-ESS group).
      The mucosal cilia taken from the maxillary sinus in 12 patients with sinusitis
      before and after ESS (paired experiments) were examined by light and electron
      microscopy. RESULTS: The radionuclide placed endoscopically in the maxillary
      sinus in eight patients immediately after ESS maintained 81.2 +/- 16.3% of its
      radioactivity after 30 minutes. This result was consistent with results in four
      patients with untreated chronic sinusitis in whom the radionuclide had been
      instilled by antral puncture (86.9% +/- 3.5%). On the other hand, in six patients
      in the post-ESS group the radionucleotide maintained only 25.9% +/- 11.6% of its
      radioactivity, demonstrating statistically significant differences from those of
      both the sinusitis group without ESS (p < 0.005) and the group 4 days after ESS
      (p < 0.005). The absence of the cilia in the sinusitis condition was recognized
      in 35.5% +/- 12.1% (n = 12) of the epithelial cells. On the other hand, the
      absence of cilia was significantly (p < 0.01) reduced to 5.3% +/- 3.7% of the
      epithelial cells in the post-ESS condition. Electron microscopic observation also
      revealed abnormal cilia in the sinusitis condition, whereas the mucosal cilia
      were regularly arranged in the post-ESS condition. CONCLUSIONS: The mucociliary
      clearance of the maxillary sinus disturbed by chronic inflammation was restored
      by ESS, indicating the clinical effectiveness of ESS for the treatment of chronic
      sinusitis.

PMID- 9003211
TI  - High frequency of a deletion polymorphism of the angiotensin-converting enzyme
      gene in asthma.
AB  - BACKGROUND: An insertion-deletion polymorphism of the angiotensin-converting
      enzyme (ACE) gene has been shown to be associated with levels of ACE. Because ACE
      is heavily expressed in the lungs and plays a key role in the metabolism of
      angiotensin II and bradykinin, which are potentially involved in the pathogenesis
      of asthma, we tested the hypothesis of an association between the polymorphism of
      the ACE gene and asthma. METHODS: Seventy-nine patients with asthma, 54 healthy
      subjects, and 33 patients with nonasthmatic lung disease were studied. Pulmonary
      function tests were performed in patients with asthma, and the ACE genotypes were
      determined in all subjects by the polymerase chain reaction. RESULTS: The ACE
      genotype distribution was similar in healthy subjects and in patients without
      asthma. By contrast, the population of patients with asthma was characterized by
      a higher prevalence of the DD genotype of ACE (odds ratio, 2.09; 95% confidence
      interval, 1.05 to 4.16; p = 0.023). No difference in pulmonary function test
      results was detected in asthmatic patients according to the distribution of ACE
      genotypes. CONCLUSION: This study reports an association between the DD genotype
      of ACE and asthma, which is not related to the degree of airway obstruction.
      These results need to be confirmed by a larger case-control study.

PMID- 9003212
TI  - Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and
      may be modulated by nasal glucocorticoids.
AB  - Nitric oxide (NO) is produced in large amounts in the noses of normal
      individuals. We have measured NO by chemiluminescence in the noses and exhaled
      air of subjects with symptomatic allergic rhinitis, some of whom had concomitant
      asthma, during the pollen season and compared this with values measured in normal
      subjects and in patients treated with nasal and/or inhaled glucocorticoids. We
      found that nasal levels of NO were significantly (p < 0.001) elevated in patients
      with untreated rhinitis (1527 +/- 87 ppb, n = 12) compared with normal
      individuals (996 +/- 39 ppb, n = 46) or subjects treated with nasal steroids (681
      +/- 34 ppb, n = 10), whereas exhaled NO in patients with untreated rhinitis was
      similar to that in normal subjects (10 +/- 2 ppb vs 7 +/- 0.6 ppb, respectively).
      In five subjects who were nasally challenged with allergen, there was a
      significant decrease in nasal NO 1 hour after challenge, and this was
      significantly correlated with increased rhinitis symptoms. In patients with
      rhinitis and concomitant asthma, nasal NO was also significantly elevated (1441
      +/- 76 ppb, n = 16) but not when they were treated with nasal or inhaled
      steroids; whereas exhaled NO was elevated in untreated patients and in patients
      treated with nasal, but not inhaled, steroids. Our data suggest that the increase
      in exhaled NO in patients with allergic rhinitis is likely to be due to increased
      local production, caused by long-term exposure to allergen, which is suppressed
      by locally administered steroids. Measurement of nasal NO may be useful to study
      the inflammatory response in rhinitis and its response to antiinflammatory
      treatments.

PMID- 9003213
TI  - A comparison of cytokine release from epithelial cells cultured from nasal biopsy
      specimens of atopic patients with and without rhinitis and nonatopic subjects
      without rhinitis.
AB  - BACKGROUND: Recent studies have suggested that airway epithelial cells of atopic
      and nonatopic individuals may differ in their ability to produce proinflammatory
      cytokines. METHODS: We have cultured human nasal epithelial cells (NECs) as
      confluent explant cultures from nasal biopsy specimens of well-characterized
      nonatopic normal volunteers without rhinitis (n = 8), atopic volunteers without
      rhinitis (n = 9), and atopic patient volunteers with rhinitis (n = 10) and
      measured the amounts of IL-1 beta, IL-8, granulocyte-macrophage colony
      stimulating factor, tumor necrosis factor-alpha, and RANTES released
      spontaneously into the culture medium by these cells in vitro. NECs from patients
      with allergic rhinitis were cultured from biopsy specimens obtained on two
      different occasions, during and after the pollen season. RESULTS: In general,
      NECs from atopic individuals released significantly greater amounts of IL-1 beta,
      IL-8, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor
      alpha, and RANTES than NECs from nonatopic individuals. IL-8 was released in
      greatest quantity and IL-1 beta in lowest quantity, regardless of whether the
      NECs were derived from atopic or nonatopic volunteers. Of the atopic individuals,
      NECs of atopic patients with rhinitis naturally exposed to pollen released
      greater quantities of all these cytokines, compared with NECs of atopic patients
      with rhinitis and atopic patients without rhinitis who were not exposed to
      allergen. CONCLUSIONS: These results suggest that NECs of atopic individuals, who
      are genetically predisposed to upper airway disease, release increased amounts of
      proinflammatory cytokines and that natural exposure to allergen enhances the
      release of these cytokines, exacerbating the symptoms of allergic disease.

PMID- 9003214
TI  - Treatment with hot, humid air reduces the nasal response to allergen challenge.
AB  - Ten subjects with asymptomatic seasonal allergy, outside of their allergy season,
      underwent allergen provocation following 1 hour of exposure to air at either 20
      degrees C and 30% relative humidity (RH) or air at 37 degrees C and 90% RH. The
      ipsilateral changes following antigen challenge were compared under the two
      conditions. Conditioning of the nose to 37 degrees C, 90% RH reduced total
      histamine release (7.9 +/- 1.8 ng vs 4.2 +/- 1.3 ng; p < or = 0.05), sneezes (6
      +/- 2 vs 3 +/- 1; p < or = 0.05), pruritus (score of 17.4 +/- 6.0 vs score of 2.0
      +/- 1.8 out of a total score of 100, p < or = 0.01), nasal airway resistance (1.4
      +/- 0.8 kPa/L/sec vs 0.2 +/- 0.1 kPa/L/sec; p < or = 0.05), human serum albumin
      levels (389.6 +/- 53.4 micrograms vs 242.2 +/- 37.9 micrograms; p < or = 0.05),
      and congestion (score of 23.8 +/- 4.8 vs score of 10.6 +/- 5.4 out of a total
      score of 100, p < or = 0.01). It had no effect on the volume of secretions (p =
      0.8), lactoferrin levels (p = 0.3), or rhinorrhea (p = 1.0). Thus air at 37
      degrees C and 90% RH partially reduces the early response to antigen. Its effects
      are greatest on histamine release, the vascular response, and neural responses,
      with no effect on the glandular response. The mechanisms underlying these effects
      are unknown.

PMID- 9003215
TI  - Late allergic airway response to segmental bronchopulmonary provocation in
      allergic subjects is related to peripheral blood basophil histamine release.
AB  - BACKGROUND: Basophil histamine release has been found to correlate with the
      presence and severity of allergic disease. However, it remains to be established
      whether airway response to antigen is related to basophil involvement and its
      release of histamine. OBJECTIVE: The purpose of this study was to investigate
      whether the intensity of airway response to an inhaled antigen challenge in
      allergic subjects is related to IgE-dependent peripheral blood basophil histamine
      release. METHODS: The response to segmental bronchoprovocation with antigen was
      examined in 34 subjects with allergic rhinitis. Bronchoalveolar lavage samples
      were obtained 5 minutes (immediate response) and 48 hours (late response) after
      allergen challenge. Peripheral blood maximal basophil histamine release (MBHR) in
      response to in vitro antigen stimulation was determined in each subject before
      segmental bronchoprovocation. RESULTS: Bronchoalveolar lavage samples obtained
      during immediate response showed an increase in histamine, whereas the late
      response was noted for a marked enhancement in airway cells, particularly
      eosinophils. Interestingly, a significant correlation (r = 0.73, p < 0.0001,
      Spearman Rank test) was noted between MBHR and intensity of bronchoalveolar
      lavage eosinophilia at 48 hours. Furthermore, subjects with high (> or = 20%)
      MBHR had significantly higher total cells and eosinophils in bronchoalveolar
      lavage fluid 48 hours after antigen segmental bronchoprovocation when compared
      with subjects with low (< 20%) MBHR. CONCLUSION: Our data suggest that the
      intensity of airway eosinophilia in response to antigen challenge is correlated
      with the magnitude of basophil mediator release in allergic subjects.

PMID- 9003216
TI  - IgE and mast cell response on intestinal allergen exposure: a murine model to
      study the onset of food allergy.
AB  - OBJECTIVE: Allergic reactions to food are characterized by enhanced allergen
      specific IgE serum levels and the activation of intestinal mast cells. Here we
      describe a murine model for the onset of food allergy and the role of cytokines
      in the regulation of food-induced IgE responses. METHODS: Mice were primed
      systemically with low doses of alum-precipitated ovalbumin. Subsequent
      intragastric challenge led to enhanced sensitization. RESULTS: Compared with
      baseline ovalbumin-specific IgE levels before challenge (0.23 +/- 0.06 optical
      density [OD] units), ovalbumin-challenged mice showed significantly elevated IgE
      levels (0.86 +/- 0.23 OD units) after intragastric challenge, which were not
      observed in control animals (0.29 +/- 0.06 OD units). IgE levels mirrored
      intestinal mast cell activation, measured by decreased histamine levels in
      duodenal specimens, in ovalbumin-challenged mice (92.6 +/- 7.9 ng/0.1 gm tissue
      weight) but not in saline-challenged mice (135.4 +/- 18.3 ng/0.1 gm tissue
      weight), compared with baseline levels (141.1 +/- 4.1 ng/0.1 gm tissue weight).
      Changes in IgE and histamine levels after intragastric challenge could be blocked
      by treating the animals with neutralizing antibodies against IL-4 or IL-10.
      Although it is generally accepted that ingestion of food allergens leads to a
      state of immunologic unresponsiveness (i.e., oral tolerance), it is shown here
      that low-dose systemic priming followed by intragastric challenge leads to
      sensitization instead of unresponsiveness. CONCLUSIONS: Our murine model shows an
      important correlation between TH2 cytokines, IgE production, and histamine
      release. Hence, this in vivo model provides a useful tool with which the complex
      mechanism underlying sensitization to food allergens can be studied.

PMID- 9003217
TI  - Major cat and dog allergens share IgE epitopes.
AB  - BACKGROUND: Patients allergic to cats and dogs frequently display IgE reactivity
      against allergens from different animals, suggesting a cross-sensitization to
      common allergenic determinants. Although albumins have been recognized as
      relevant cross-reactive allergens, little is known regarding cross-reactive
      epitopes of the major cat and dog allergens. OBJECTIVE: In this study, sera from
      patients allergic to cats and/or dogs were used to investigate the presence of
      common IgE epitopes among the major cat and dog allergens. METHODS: The IgE
      reactivity profile of 109 patients who were allergic to allergens from several
      species of animals was determined with nitrocellulose-blotted cat and dog
      allergens. Sera from patients who were strongly allergic to the major cat and dog
      allergens were tested for the presence of cross-reactive IgE antibodies by one
      dimensional and two-dimensional immunoblot inhibition experiments and by
      quantitative measurements obtained with the CAP-FEIA system (Pharmacia). RESULTS:
      Sixty-eight of 109 patients with animal allergy showed IgE reactivity to cat
      allergens and dog allergens. Sera from patients with both cat and dog allergy
      detected allergens of similar molecular weight in nitrocellulose-blotted cat and
      dog hair/dander extracts. Common, as well as species-restricted, IgE epitopes of
      the major cat and dog allergens could be demonstrated by IgE inhibition studies.
      CONCLUSION: Shared IgE epitopes of the major cat and dog allergens may provide an
      explanation for the clinical observation that allergies to cats and dogs are
      frequently associated.

PMID- 9003218
TI  - Dust and airborne exposure to allergens derived from cockroach (Blattella
      germanica) in low-cost public housing in Strasbourg (France).
AB  - BACKGROUND: Although a strong association between allergy to cockroach (CR) and
      asthma has been observed in the United States and Asia, there are little data
      about the extent of exposure to CR allergen in Europe. OBJECTIVE: To determine
      the levels of CR allergens in dust samples from apartments in Strasbourg and to
      determine the concentration and size of CR allergens in the air. METHODS: Nine
      apartments in a public housing complex were chosen on the basis of visual
      evidence of CR infestation. Levels of CR allergens (Bla g 1 and Bla g 2) in
      kitchen and mattress dust samples were measured by immunoassay with the use of
      monoclonal antibodies. Air was sampled for 3 to 8 hours in the kitchen under
      undisturbed conditions, during artificial disturbance, and during normal domestic
      activity by using an impinger and a parallel glass fiber filter and at flow rates
      of 2 to 20 L/min. Airborne CR and mite allergens were measured concurrently in
      the bedroom of one apartment before, during, and after artificial disturbance.
      RESULTS: High levels of Bla g 1 and Bla g 2 were found in kitchen dust from the
      nine apartments (geometric means of 3919 U/gm [range 530 to 14306 U/gm] and 497
      U/gm [range 73 to 1946 U/gm], respectively). Under undisturbed conditions,
      airborne CR allergens were not detectable in any of the apartments. During
      vigorous artificial disturbance, Bla g 1 and Bla g 2 were detectable in air
      samples from seven apartments (geometric means of 4.5 U/m3 [range 0.7 to 17.2
      U/m3] and 1.0 U/m3 [range 0.4 to 3.4 U/m3], respectively). Both allergens were
      predominantly collected on the first stage of the impinger, and 76% to 80% of the
      airborne allergen was associated with particles greater than 10 microns in
      diameter. The levels were significantly higher than those collected on the second
      or third stages of the impinger (p < 0.001). A comparison of the levels of mite
      and CR allergens showed that the airborne properties of these allergens were
      similar, that is, measurable only during disturbance and not detectable 30
      minutes after disturbance. CONCLUSION: Levels of CR allergen in low-cost public
      housing in Strasbourg can be as high as or higher than the levels measured in
      towns in the United States. CR allergens become airborne during disturbance and
      are primarily associated with particles greater than 10 microns in diameter.
      Patients with asthma living in urban areas of Europe in housing prone to CR
      infestation should be evaluated for sensitization and exposure to CR allergens.

PMID- 9003219
TI  - Promotion of mouse fibroblast proliferation by IgE-dependent activation of mouse
      mast cells: role for mast cell tumor necrosis factor-alpha and transforming
      growth factor-beta 1.
AB  - Pathologic fibroblast proliferation or tissue fibrosis develops in certain
      chronic allergic diseases and in a wide array of other inflammatory disorders in
      which mast cell activation is also a prominent feature. In this study we
      investigated a number of potential mechanisms by which IgE-dependent activation
      of mouse mast cells might influence the proliferation of mouse fibroblasts in
      vitro. We found that supernatants from in vitro-derived mast cells that had been
      activated by IgE and specific antigen (but not those from quiescent mast cells)
      promoted the proliferation of mouse embryonic skin or 3T3 fibroblasts, and we
      showed that this effect was detectable in the absence of fetal calf serum. We
      analyzed the kinetics with which the fibroblast-proliferative activity was
      secreted from bone marrow-derived cultured mast cells and found that it was
      released both rapidly (i.e., in 30 minutes or less) and for a more prolonged
      period (i.e., for more than 2 hours) after IgE-dependent mast cell activation. We
      then measured the levels at which the mast cells produce a number of cytokines
      that are known to affect fibroblasts (IL-1, IL-6, transforming growth factor-beta
      1 [TGF-beta 1], and tumor necrosis factor-alpha [TNF-alpha]) and assessed their
      relative effects, as recombinant cytokines, on fibroblast proliferation. Our mast
      cells secreted high levels of TGF-beta 1 and TNF-alpha, intermediate amounts of
      IL-6, and low levels of IL-1. We titrated the fibroproliferative effects of each
      of these cytokines and determined that at a dose of 50 pg/ml their rank order of
      activity was TGF-beta 1 > TNF-alpha > IL-1 > IL-6, with all but IL-6 having
      significant effects. The ability of supernatants from activated bone marrow
      derived cultured mast cells to promote fibroblast proliferation was partially
      diminished by absorption with neutralizing antibodies against either TNF-alpha or
      TGF-beta 1, and absorption of the supernatants with a combination of antibodies
      against TNF-alpha and TGF-beta 1 reduced their ability to induce fibroblast
      proliferation by approximately 50% (p < or = 0.001, n = 5). These findings show
      that IgE-dependent activation of mouse mast cells can result in the release of
      mediators that promote fibroblast proliferation in the absence of any other cell
      type and suggest that mast cell-derived TNF-alpha and TGF-beta 1 contribute
      substantially to this effect. They also suggest that these cytokines exert their
      effects through synergistic interactions with other mast cell mediators.

PMID- 9003220
TI  - Milk-responsive atopic dermatitis is associated with a casein-specific lymphocyte
      response in adolescent and adult patients.
AB  - BACKGROUND: Specific T-cell responses to food antigens have been described in
      children with atopic dermatitis (AD). However, a subgroup of adolescent and adult
      patients still experiences food-responsive AD. OBJECTIVE: This study was designed
      to evaluate lymphocyte responses to bovine casein in adult patients with AD.
      METHODS: The stimulatory capacity of lipopolysaccharide-depleted bovine casein
      was tested in proliferation assays and in limiting dilution assays. Casein
      specific T-cell clones (TCCs) were generated and characterized. RESULTS: Higher
      proliferative responses to casein and modulation of cytokine receptors were
      observed in patients with milk-responsive AD compared with individuals without
      clinical reactions on milk ingestion. The results did not correlate with the
      amount of casein-specific IgE in the serum. The frequencies of T cells that grew
      in the presence of casein or house dust mite antigens were similar. Only 27% of
      CD4+ casein-specific TCCs from these patients, but the majority of house dust
      mite-specific TCCs, produced IL-4 on mitogen stimulation. Interferon-gamma, on
      the other hand, was produced by the majority of TCCs with both specificities.
      CONCLUSION: A specific T-cell-mediated immune response to casein can be found in
      the blood of adolescent and adult patients with milk-related exacerbation of AD.
      In contrast to house dust mite-specific T cells, casein-specific T cells of adult
      patients who respond to cow's milk with worsening of AD produce little or no IL
      4.

PMID- 9003221
TI  - Analysis of an exon 1 polymorphism of the B2 bradykinin receptor gene and its
      transcript in normal subjects and patients with C1 inhibitor deficiency.
AB  - The B2 bradykinin receptor (B2BKR) mediates most of the inflammatory actions of
      bradykinin. To evaluate its potential role in allergic diseases, we assessed the
      structure of the human B2BKR gene. Screening a human placenta genomic DNA library
      identified only clones containing exons 2 and 3. Human placenta and colon tissues
      were used for 5' rapid amplification of complementary DNA ends to identify nine
      exon 1 clones, each containing one 9 bp and two 1 bp deletions compared with
      published sequences. Exon 1 genomic polymerase chain reaction of human leukocyte
      DNA revealed two distinct products, which were shown to differ by the presence or
      absence of the 9 bp deletion. Alleles with the 9 bp deletion were designated as (
      )21-29, whereas alleles without the deletion were designated as (+)21-29. Genomic
      polymerase chain reaction in 39 Caucasian, 31 African-American, and 32 Asian
      normal subjects revealed a highly significant difference in the allelic frequency
      of the two genotypes, primarily because of an absence of the (+)21-29 allele in
      Asian subjects. Analysis of steady-state B2BKR messenger RNA levels by reverse
      transcription polymerase chain reaction in heterozygous normal subjects revealed
      consistently higher expression of (-)21-29 transcripts. To investigate the
      potential clinical significance of the exon 1 polymorphism, 21 patients with
      angioedema and C1 inhibitor deficiency were genotyped. None were homozygous for
      the (+)21-29 allele (p = 0.0088 compared with normal subjects). In contrast, two
      patients with immunochemical evidence of hereditary angioedema without history of
      clinical angioedema were (+)21-29 homozygous. These results suggest that the
      B2BKR genotype may influence clinical status in diseases characterized by
      involvement of bradykinin.

PMID- 9003222
TI  - Asthma caused by Dermestidae (black carpet beetle): a new allergen in house dust.

PMID- 9003223
TI  - Evaluation of Duotip-Test.

PMID- 9003224
TI  - Acetaminophen-induced urticaria and tolerance of ibuprofen in an eight-year-old
      child.

PMID- 9003225
TI  - Fatal anaphylaxis after a yellow jacket sting, despite venom immunotherapy, in
      two patients with mastocytosis.

PMID- 9003226
TI  - Dental materials developments in the UK: a personal view.

PMID- 9003227
TI  - Differential expression of human high-molecular-weight salivary mucin (MG1) and
      low-molecular-weight salivary mucin (MG2).
AB  - Two distinct mucin components of saliva, MG1 and MG2, have been identified based
      on chemical composition and molecular weights (high and low, respectively) in
      saliva. With the aim of characterizing the expression pattern of salivary mucins,
      we have prepared monoclonal antibodies (MAbs) directed against the peptide core
      of MG1 and against a synthetic peptide derived from the MG2 (MUC7) sequence. MAb
      PANH2 raised against partially deglycosylated MG1 stained a high-molecular-weight
      smear in Western blots of partially purified MG1. PANH2 binding was increased by
      deglycosylation with trifluoromethanesulfonic acid as well as with subsequent
      periodate treatment, and was eliminated by pronase treatment, strongly suggesting
      that MAb PANH2 was directed to a peptide epitope of MG1. MAb PANH3 raised against
      a synthetic peptide derived from the MG2 (MUC7) sequence reacted with the native
      molecule and stained a narrow smear of ca. 200,000 to 210,000 in Western blots of
      concentrated saliva and a lower-molecular-weight smear of
      trifluoromethanesulfonic-acid-treated MG2. Immunohistology on frozen sections of
      human salivary glands showed that MAb PANH2 selectively labeled mucous cells,
      whereas MAb PANH3 labeled subpopulations of serous cells. Double-direct
      immunofluorescence staining with PANH2 and PANH3 demonstrated that the staining
      patterns were non-overlapping. The development of these antibody probes will
      facilitate studies of mucin expression in diseases of salivary glands.

PMID- 9003229
TI  - A morphometric investigation of myotube formation in rabbit embryo medial
      pterygoid muscle.
AB  - To determine the times of the appearance of myoblasts, early myotubes, late
      myotubes, and myofibers, we studied a region between two aponeuroses of the
      medial pterygoid masticatory muscle in embryos of two strains of rabbits, without
      disturbing the normal innervation. The objectives of this study were to define
      the quantitative relations among these cells and to determine their kinetics
      statistically. We used Fauve de Bourgogne and New Zealand rabbit embryos on day
      17, day 17 plus 12 hours, day 18, day 18 plus 12 hours, and days 20, 22, and 28
      of gestation. Cell proliferation was studied with a light microscope, by means of
      counting methods. Similar development was observed in the two strains of rabbits.
      The numbers of myoblasts decreased as follows: (i) a marked decrease; (ii) a
      sudden cessation of the decrease, marked by a rebound at 18 days, and lasting
      less than 24 hours; and (iii) a plateau between embryonic days 22 and 28. The
      onset of reduction in the number of early myotubes coincided with the rebound of
      myoblasts. The number of late myotubes increased at the time of maximal early
      myotube density and during rebound of the myoblasts. Myofiber densities were
      similar to late myotube densities on day 22. We suggest that early myotubes are
      formed very gradually by fusion of myoblasts, and that the significant increase
      in the numbers of myoblasts corresponds to the second generation of myoblasts
      necessary for differentiation of late myotubes.

PMID- 9003228
TI  - Chemokine expression in human oral keratinocyte cell lines and keratinized
      mucosa.
AB  - Chemoattractant cytokines regulate the immune response within the tissue by
      recruiting neutrophils and macrophages. These so-called chemokines include a
      large family of peptide molecules encoded by distinct genes. Their expression is
      controlled by a variety of microbial and host factors. Among host factors,
      interleukin-1 (IL-1) is thought to be a key regulator of tissue destruction and
      mediator of the local immune response. To study its influence on chemokine
      expression, we used a highly sensitive, semi-quantitative method to assess gene
      expression at the level of mRNA. RNA was extracted from human oral keratinocyte
      cell lines after treatment with recombinant human IL-1. To test the method
      further and possibly establish a chemokine mRNA expression pattern, we also
      extracted RNA from healthy oral keratinized mucosa. Purified RNA was reverse
      transcribed and subsequently amplified in a polymerase chain reaction (RT-PCR) by
      means of specific primer pairs. Amplified sequences were analyzed by agarose gel
      electrophoresis, visualized by ethidium bromide staining, transferred to nylon
      membranes, and hybridized to biotinylated oligonucleotide probes. Detection was
      achieved by streptavidin-conjugated alkaline phosphatase, a chemiluminescent
      substrate, and autoradiography. Autoradiographs were analyzed by densitometric
      measurements. IL-1 stimulation resulted in an increase of the chemokine mRNAs
      encoding interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and
      GRO gamma. Macrophage inflammatory protein-1 alpha (MIP-1 alpha) mRNA was not
      detectable in keratinocytes. In healthy oral mucosa, we found considerable
      variation between the subjects. Detection of chemokine mRNAs by RT-PCR proved to
      be sensitive, specific, and fast. It allows for the study of not only cell-line
      derived RNA, but also of RNA isolated directly from biopsy material. The latter
      feature makes this method well-suited for diagnostic purposes.

PMID- 9003230
TI  - Anatomic and directional variation in the mechanical properties of the mandibular
      condyle in pigs.
AB  - Stereologic studies of trabecular architecture suggest that the pig mandibular
      condyle is strongest when loaded supero-inferiorly, and that stress is
      concentrated in the antero-inferior region (Teng and Herring, 1995). To test
      these hypotheses, we investigated the uni-axial mechanical properties of 22 pig
      mandibular condyles in three loading directions at a mean strain rate of 0.14 (+/
      0.12)% s-1. A total of 91 rectangular beam specimens (averaging 9.0 mm x 6.0 mm
      x 5.0 mm) was tested. For each specimen, 5 or 6 non-destructive tests were
      performed before compressive failure. Strain in both longitudinal and transverse
      directions was measured by foil strain gauges on the central part of the
      specimen. Data were normalized at a strain rate of 0.1% s-1, specimen length of 9
      mm, and cross-sectional area of 30.25 mm2. Generally, modulus of elasticity (E)
      and ultimate stress (sigma u) in the anterior regions of the condyle were greater
      than those in the posterior. E, sigma u, and Poisson's ratio (upsilon) were
      significantly different among the test directions, but ultimate strain (epsilon
      u) was not. The highest values of E (4.04 GPa), sigma u (14.97 MPa), and rho
      (0.81 g/cm3) were seen in the anterior inferior/middle region under supero
      inferior loading. The lowest values (0.94 GPa for E, 2.38 MPa for sigma u, and
      0.52 g/cm3 for rho) were found in the inferior/posterior region in medio-lateral
      loading. Although the mechanical properties of the condyle vary depending upon
      location, these results verify that the condyle is strongest and stiffest under
      compressive loads in the supero-inferior direction, and that the anterior
      inferior region is particularly strong and stiff.

PMID- 9003232
TI  - Adhesive bonding to dentin with ferrous chloride primers and tri-n-butylborane
      initiated luting agents.
AB  - A variety of surface modifications with metal chlorides has been used to enhance
      the bond of resins to dentin. This study investigated the effectiveness of
      ferrous chloride in terms of the initiation of polymerization in dentin bonding.
      The efficacy of experimental dentin primers was evaluated via the bonding of two
      luting agents to dentin. The 16 primers evaluated were ferrous chloride (FeCl2)
      aqueous solutions, eight with and eight without 35% 2-hydroxyethyl methacrylate
      (HEMA). The concentrations of FeCl2 in the primers ranged from 2.0 x 10(-6) to
      5.0 x 10(-4) mol/g. One luting agent (Super-Bond C&B) consisted of methyl
      methacrylate (MMA), 4-methacryloyloxyethyl trimellitate anhydride (4-META), and
      tri-n-butylborane (TBB) initiator. The other luting agent was prepared with MMA
      and TBB, but without 4-META. Bovine dentin surfaces were flattened, etched with
      an aqueous solution of 10% phosphoric acid, primed, and then bonded with
      stainless steel rods. Tensile strengths of the bonded specimens were measured
      after one-day immersion in water. Tensile testing revealed that the bond strength
      was influenced by the application of FeCl2 and/or HEMA. The maximum bond strength
      of 33.0 MPa was recorded with the use of primer containing FeCl2 and HEMA in MMA
      TBB resin. In the case of Super-Bond, only surface treatment of dentin with
      aqueous primers containing 5.0 x 10(-5) to 2.0 x 10(-4) mol/g ferrous chloride
      resulted in bond strength values above 22.0 MPa. This bonding technique,
      combining the use of ferrous chloride primer with Super-Bond resin, may
      potentially be applied for seating resin-bonded restorations.

PMID- 9003231
TI  - The effects of acetone, ethanol, HEMA, and air on the stiffness of human
      decalcified dentin matrix.
AB  - During resin-bonding procedures, dentin surfaces are treated with acidic
      conditioners to remove the smear layer and decalcify the surface to expose the
      collagen fibrils of the underlying matrix. These decalcified surfaces are then
      either air-dried or treated with dehydrating solvents, procedures which may
      modify the physical properties of the dentin matrix. The purpose of this study
      was to evaluate the effects of dehydration on the stiffness of the decalcified
      dentin matrix. Small (8 x 1.7 x 0.9 mm) beams of dentin were prepared from mid
      coronal dentin of extracted human molars. The ends were covered with varnish for
      protection, and the specimens were placed in 0.5 M EDTA for 5 days to decalcify.
      The stiffness was measured by both the cantilever technique and by conventional
      stress-strain testing. Specimens tested by the cantilever technique were
      sequentially exposed to water, acetone, alcohol, HEMA, and glutaraldehyde.
      Specimens tested by conventional stress-strain testing were exposed either to
      water, acetone, or HEMA, or were allowed to air-dry. The results indicate that
      the stiffness of decalcified human dentin matrix is very low (ca. 7 MPa), if the
      specimens are wet with water. As they are dehydrated, either chemically in water
      miscible organic solvents or physically in air, the stiffness increases 20- to 38
      fold at low strains or three- to six-fold at high strains. These increases in
      modulus were rapidly reversed by rehydration in water. Exposure to glutaraldehyde
      also produced an increase in stiffness that was not reversible when the specimens
      were placed back in water.

PMID- 9003233
TI  - Surface spectroscopy of apatitic materials: limitations and concerns.
AB  - The use of x-ray photoelectron spectroscopy for the study of biological materials
      has provided mixed results. The experimental difficulties associated with the
      application of this technique to the study of biological materials include the
      effects of ultra-high vacuum, x-ray exposure, surface charging, and, for
      insulating materials, the inherent lack of an intrinsic energy reference. Since
      most biological materials are insulators, the lack of an intrinsic energy
      reference complicates one's ability to draw direct comparisons between different
      studies. In this paper, the results from two different apatites are compared with
      the results obtained from the use of two conventional techniques for referencing
      binding energies. The results presented here are referenced only to the Pt Fermi
      level; no further energy modifications are performed. A comparison with the
      results of other investigators indicates a large difference in binding energies
      for all involved core levels. These results indicate that, in the study of
      insulating materials with x-ray photoelectron spectroscopy, it is essential that
      all data be acquired under exacting conditions on the same experimental system.

PMID- 9003234
TI  - Impedance spectroscopy of teeth with and without approximal caries lesions--an in
      vitro study.
AB  - Caries diagnosis by the measurement of electrical resistance is hampered by
      polarization effects when dc or single-low-frequency ac currents are used.
      Electrical impedance spectroscopy, measuring impedance over a large range of
      frequencies, will provide more detailed information about the electrical
      characteristics of teeth. It was the aim of this study (a) to characterize the
      complex impedance behavior of whole extracted teeth, measured at the approximal
      surface, and (b) to identify parameters of the complex impedance behavior of the
      teeth which would be useful in distinguishing between degrees of carious
      involvement. Thirty-nine extracted premolar teeth with 59 unrestored and
      undamaged (excepting caries) approximal surfaces were selected. The tooth
      surfaces were divided into three groups according to their macroscopic
      appearance: sound (group S, n = 16), white- or brown-spot lesion present (group
      L, n = 33), or cavitated (group C, n = 10). The teeth were inserted into a jig
      which allowed for counter-electrode contact via a conducting gel. The working
      electrode consisted of a carbonated fiber material. Electrical impedance
      measurements were performed over a maximum range of about 1 MHz to 0.1 Hz. We
      analyzed electrical impedance data by fitting equivalent circuits. Fit was
      evaluated numerically and visually. The complex impedance spectra divided
      naturally into three groups which corresponded almost perfectly with the
      classifications of S,L, and C. The groups differed most in the dc resistance
      (Rdc), as calculated from the impedance parameters. Mean Rdc for groups S, L, and
      C were 68 M omega, 5.9 M omega, and 321 k omega, respectively. These means were
      significantly different from each other (log-transformed data, ANOVA, p < 0.001;
      Tukey multiple comparisons, p < 0.001). It is concluded that the in vitro
      performance of electrical impedance spectroscopy in differentiating among sound,
      non-cavitated carious, and cavitated approximal tooth surfaces is excellent.

PMID- 9003235
TI  - Taste preference for sweetness in urban and rural populations in Iraq.
AB  - The consumption of sweetened foods is influenced by a variety of biological,
      psychological, sociological, and environmental factors. On an individual level,
      taste preference for sweetness has been shown to have an influence on food
      consumption, although this may be affected by social and environmental factors.
      The aim of this study was to assess the taste preference for sweetness in urban
      and rural populations in Iraq. The hypothesis was that sweet preference and the
      consumption of sugar increase with urbanization. The sample was composed of 4152
      individuals who were divided into urban and rural subgroups based on their place
      of residence. Sweet preference was assessed by means of a tested Sweet Preference
      Inventory. Results revealed statistically significant differences between urban
      and rural populations in preference for sweetness and in actual sugar
      consumption. Individuals from urban locations showed a much higher preference for
      sweetness than their rural counterparts and consumed more sugar. Within the urban
      population, those individuals who had lived in the city longer and who were from
      families with lower educational qualifications preferred the highest levels of
      sugar. The findings support the hypothesis that urbanization influences sweet
      preference and sugar consumption.

PMID- 9003236
TI  - Accumulation of fermentable sugars and metabolic acids in food particles that
      become entrapped on the dentition.
AB  - Earlier studies (Kashket et al., 1991) showed that particles of high-starch snack
      foods remained longer on the teeth than those of high-sucrose, low-starch foods.
      The question arose whether the prolonged presence of food particles enhances
      cariogenicity. A study was undertaken to measure sugars, starches, and metabolic
      acids in retained food particles. Subjects consumed portions of different foods,
      and particles were removed from all bicuspids and first molars at defined times
      after swallowing. Dry weights, sugars, and short-chain carboxylic acids were
      determined. High-sucrose foods were cleared rapidly from the teeth, while high
      starch foods were retained for up to 20 min. Sucrose, glucose, and fructose
      persisted in the retained particles. Particles of high-starch foods accumulated
      maltose and maltotriose, presumably from the breakdown of starch by salivary
      amylase. At maximum, maltose plus maltotriose constituted 94% of total sugars in
      particles of potato chips; corresponding values in doughnuts, peanut butter
      cookies, and salted crackers were 43, 51, and 61%, respectively. Total
      fermentable sugars in the particles of high-starch foods were similar to those
      for the high-sucrose confectionery products. Carboxylic acids accumulated within
      the particles, presumably due to the fermentation of the sugars by entrapped
      salivary micro-organisms. At maximum (5 to 7 min), acetic, formic, lactic, and
      propionic acids rose 17-, 30-, 15-, and 1.3-fold, respectively, in doughnuts, and
      to smaller degrees in potato chips, salted crackers, and chocolate-caramel-peanut
      bars. In summary, the study demonstrated the persistence of sugars, the
      progressive accumulation of starch breakdown products, and the fermentation of
      the accumulated sugars in retained food particles. The findings support the view
      that high-starch foods contribute to the development of caries lesions.

PMID- 9003237
TI  - Emergence of multiple xylitol-resistant (fructose PTS-) mutants from human
      isolates of mutans streptococci during growth on dietary sugars in the presence
      of xylitol.
AB  - The growth inhibition of mutans streptococci is one of the proposed mechanisms of
      action of xylitol, a caries-preventive natural carbohydrate sweetener. Xylitol is
      taken up and accumulated as non-metabolizable, toxic xylitol phosphate via a
      constitutive fructose PTS, and selects, during in vitro growth at the expense of
      glucose, for natural xylitol-resistant mutants that lack constitutive fructose
      PTS activity. Since long-term xylitol consumption leads to the emergence of
      xylitol-resistant mutans populations in humans in an oral environment containing
      sugars of dietary origin, we wanted to test the hypothesis that xylitol-resistant
      cells could be selected from mutans streptococci strains during in vitro growth
      on fructose, sucrose, or lactose. Three laboratory strains and three fresh mutans
      streptococcal isolates were repeatedly transferred in trypticase-yeast extract
      medium supplemented with glucose, fructose, sucrose, or lactose in the presence
      and absence of xylitol. Depending on the growth sugar, the presence of xylitol
      resulted in the selection of xylitol-resistant populations for several of the six
      strains tested, but not necessarily in the presence of all four sugars. All six
      strains rapidly became xylitol-resistant when grown on glucose in the presence of
      xylitol. All three fresh isolates became xylitol-resistant after 9 to 16
      transfers in the presence of fructose or sucrose plus xylitol, while none of the
      laboratory strains became xylitol-resistant after 16 transfers in the presence of
      these sugars. The growth rates of 12 xylitol-resistant mutants in the presence of
      eight sugars suggested the existence of various types of xylitol-resistant
      mutants. The data partially explain the occurrence of xylitol-resistant mutans
      populations in long-term xylitol consumers and suggest a mechanism consistent
      with a selection process. Since various preliminary results suggest that xylitol
      resistant natural mutants may be less virulent and less cariogenic than their
      parent strains, this selection process may alter, for the better, the mutans
      streptococci population of the plaque and play a role in the caries-preventive
      action of xylitol.

PMID- 9003238
TI  - Plaque pH and microflora of dental plaque on sound and carious root surfaces.
AB  - Given the hypothesis that root caries is the result of acid formation by
      acidogenic micro-organisms, the present study was performed to relate sucrose
      induced pH response of dental plaque on root surfaces to the microbial
      composition of the overlying plaque. Seventeen caries-active elderly Chinese with
      poor oral hygiene and with both sound and carious root surfaces were examined.
      Plaque pH was measured before and up to one hour after a controlled sucrose
      mouthrinse. Plaque samples for microbiologic analyses were collected from 2 sound
      and 2 or 3 carious pH-measurement sites in each subject. The prevalence of the
      following micro-organisms was assessed as % of total viable counts on Brucella
      agar: Prevotella intermedia, Prevotella melaninogenica, Fusobacterium nucleatum,
      Campylobacter rectus, Capnocytophaga spp., Actinomyces viscosus, Actinomyces
      naeslundi, Streptococcus spp., S. sanguis, S. mitis, S. mutans, S. sobrinus,
      Lactobacillus spp., and Candida spp. There was no difference in plaque pH
      response on sound and carious root surfaces. The plaque pH response was more
      pronounced in the maxilla than in the mandible for both sound and carious sites.
      There was no difference in microbial composition of dental plaque on sound and
      carious root surfaces. The pH response to sucrose was the same regardless of the
      presence or absence of mutans streptococci. Our results thus do not readily
      support the traditional concept of caries formation.

PMID- 9003240
TI  - Suppression of experimental autoimmune encephalomyelitis (EAE) by intraperitoneal
      administration of soluble myelin antigens in Wistar rats.
AB  - Intraperitoneal (i.p.) treatment of Wistar rats with bovine myelin (BM) or myelin
      basic protein (MBP) previously to immunization with BM-CFA showed a diminished
      incidence and severity of experimental autoimmune encephalomyelitis (EAE) (2/13
      and 0/7, respectively) when compared with rats immunized with BM-CFA (11/17) or
      i.p. treated with ovalbumin (2/4). Concomitantly, animals treated with BM or MBP
      exhibited a marked reduction of proliferative response to MBP which was highly
      positive when spleen mononuclear cells from nontreated and ovalbumin treated
      animals were assayed. Rats that were treated with MBP before immunization produce
      IgA, IgM, total IgG and subclasses of IgG, IgG2a, IgG2b, IgG2c specific for MBP
      in similar levels than those observed in nontreated immunized animals. However, a
      higher incidence and level of IgG1 was observed in MBP treated rats, meanwhile
      rats i.p. treated with total BM showed a highly reduced humoral response. The
      herein presented results show that i.p. treatment with low amounts of soluble
      forms of myelin antigens markedly reduced the clinical symptoms of the disease,
      the histological alterations, the cellular proliferative response to MBP, and
      produced changes in the autoimmune humoral response.

PMID- 9003241
TI  - beta-Interferon regulates the immunomodulatory activity of neonatal rodent
      microglia.
AB  - beta-interferon (beta-IFN) has both pro and anti-inflammatory properties, the
      balance of which leads to some suppression of disease activity in multiple
      sclerosis patients. Here, we examine the immunomodulation of neonatal rodent
      microglia, the principal CNS accessory cell, by beta-IFN and consider the
      interaction of beta-IFN and gamma-interferon (gamma-IFN). beta-IFN and gamma-IFN
      inhibit microglial proliferation. beta-IFN antagonises both gamma-IFN-induced
      upregulation of class II expression and the ability of gamma-IFN primed cells to
      mount a respiratory burst. In contrast, beta-IFN upregulates microglial Fc
      receptor expression and augments tumour necrosis factor alpha secretion from
      suboptimally stimulated microglia.

PMID- 9003242
TI  - Exon 2 containing myelin basic protein (MBP) transcripts are expressed in lesions
      of experimental allergic encephalomyelitis (EAE).
AB  - Exon 2 containing myelin basic protein (MBP) transcripts are expressed during
      developmental myelination in mice and humans, and during remyelination subsequent
      to virally induced demyelination in adult mice. Since remyelination characterizes
      CNS lesions during experimental allergic encephalomyelitis (EAE) and multiple
      sclerosis (MS), we investigated whether exon 2 containing isoforms of MBP are
      expressed in EAE lesions during relapsing disease. Exon 2 containing MBP
      transcripts were detected by in situ hybridization in 17 of 52 EAE mice and in 16
      of 30 mice at the peak of the first or second episode of paralysis. Thus exon 2
      containing MBP transcripts are expressed in lesions of the CNS during active
      phases of chronic relapsing autoimmune disease. Implications of these findings
      with respect to future therapies aimed toward enhancing remyelination in EAE and,
      possibly MS, are discussed.

PMID- 9003245
TI  - IgM anti-GM1 antibodies in the Guillain-Barre syndrome: a serological predictor
      of the clinical course.
AB  - It has been suggested that antibodies against GM1 are involved in the
      pathogenesis of the Guillain-Barre syndrome (GBS). Recently, we have developed a
      standardized ELISA assay for anti-GM1 antibodies of IgM type well-suited for
      longitudinal patient studies. The relationship between serum antibodies against
      GM1 and Campylobacter jejuni was investigated in patients with GBS and in
      patients with C. jejuni infection. Patients with a short-lasting anti-GM1
      elevation had a fast recovery, whereas patients with slow recovery had a long
      lasting anti-GM1 elevation. A linear relationship was found between significant
      clinical recovery and the time until the anti-GM1 peak was halved (R = 0.9, p <
      0.01). The absolute level of anti-GM1 did not predict the length of the recovery
      nor was the level of anti-GM1 related to the clinical disability at its nadir.
      Our data indicate that monitoring of the IgM anti-GM1 level can predict clinical
      recovery in GBS patients.

PMID- 9003246
TI  - Evolution of neuroendocrine thymus: studies on POMC-derived peptides, cytokines
      and apoptosis in lower and higher vertebrates.
AB  - In previous papers, we showed that neuroendocrine cells reactive to anti-POMC
      derived peptides and cytokines are present in the thymus of a fish and an anuran
      amphibian. Here we report that this phenomenon is general, as neuroendocrine
      cells positive to anti-POMC-derived peptides (ACTH, beta-endorphin, alpha-MSH)
      and cytokines (IL-1 alpha, IL-2, IL-6, TNF-alpha) are also present in the thymus
      of chicken and rat. However, the number and the intrathymic localization and
      distribution of these cells varies in the different species examined. An analysis
      of apoptotic cells or cells involved in apoptosis, such as interdigitating cells
      and macrophages, in fish, frog, chicken and rat thymus, using an
      immunocytochemical method and anti-DNA mAb conjugated with peroxidase (anti-DNA
      POD), showed that cells positive to anti-DNA-POD mAb are present in the same
      thymic areas in which POMC-derived peptides and cytokines were found. In
      conclusion, these data on apoptotic cells in the thymus of lower and higher
      vertebrates are compatible with the hypothesis that neuroendocrine cells might
      play a role in the selection and apoptosis of thymic lymphocytes, a phenomenon
      which could vary slightly in different species and taxa.

PMID- 9003244
TI  - Differential localization of three distinct binding sites for sigma receptor
      ligands in rat spleen.
AB  - In vitro receptor autoradiography was used to localize sigma 1 receptors, sigma 2
      receptors, and novel haloperidol/DTG-inaccessible sites for sigma and opiate
      ligands in rat spleen. Sigma-1 receptors were present throughout the spleen, but
      were most concentrated in the T cell zones. Binding under "sigma 2 receptor
      selective' conditions was 70% nonspecific, and sigma 2 receptors could not be
      detected. Haloperidol/DTG-inaccessible sites had a coarse, punctate distribution
      in the red pulp and marginal zones of the white pulp. This anatomical
      localization suggests types of cells and functions that should be examined for
      modulation by sigma receptors.

PMID- 9003243
TI  - Antigen presentation by autoreactive proteolipid protein peptide-specific T cell
      clones from chronic progressive multiple sclerosis patients: roles of co
      stimulatory B7 molecules and IL-12.
AB  - To assess the role of T cell antigen (Ag) presentation in multiple sclerosis
      (MS), proteolipid protein (PLP) peptide reactive CD4+ T cell clones (TCCs) from
      MS patients and normal subjects were studied. TCCs derived from chronic
      progressive (CP) MS patients were able to proliferate and secret cytokines in
      response to PLP peptide stimulation in the absence of professional antigen
      presenting cells (APCs), suggesting that these T cells can simultaneously present
      and respond to Ags. However, they did not respond to total PLP protein,
      suggesting that PLP-peptide TCCs were unable to process and present the whole PLP
      molecule. The ability of the different TCCs to act as APCs in response to Ag
      stimulation did not correlate with expression of HLA-class II molecules. However,
      the degree of expression of B7-1 and B7-2 co-stimulatory molecules showed a
      significant correlation with APC capacity. Furthermore, a combination of anti-B7
      1 and anti-B7-2 mAbs effectively inhibited proliferative responses as well as
      secretion of IL-10, IFN gamma and TGF beta induced by antigen presenting T cells.
      By contrast, IL-4 secretion was not affected. Finally, IL-12 significantly
      enhanced the efficiency of T cell Ag presentation by a pathway independent of Ag
      processing, suggesting that IL-12 might act as an additional co-stimulatory
      signal for T cell activation during T-T cell interactions. Together, these
      observations suggest that Ag presentation by T cells might amplify and perpetuate
      an autoimmune response previously initiated by professional APCs. These
      properties may account for progression of MS into a CP phase.

PMID- 9003248
TI  - Analysis of B7-1 and B7-2 costimulatory ligands in cultured mouse microglia:
      upregulation by interferon-gamma and lipopolysaccharide and downregulation by
      interleukin-10, prostaglandin E2 and cyclic AMP-elevating agents.
AB  - Recent evidence indicates that membrane-bound costimulatory molecules of the B7
      family are important for T-cell activation and are upregulated in IFN gamma
      stimulated human microglia and in multiple sclerosis active lesions. In this
      study we have performed a detailed analysis of B7-1 and B7-2 expression and
      regulation in cultured mouse glial cells using immunocytochemical and semi
      quantitative reverse transcriptase-polymerase chain reaction techniques. In an
      immortalized mouse microglial cell line (BV-2), expression of B7-1 and B7-2 was
      enhanced by interferon-gamma (IFN gamma). IFN gamma was a weak inducer of B7-2
      mRNA and immunoreactivity in microglia primary cultures obtained from the
      neonatal mouse brain, whereas lipopolysaccharide, tumour necrosis factor-alpha,
      colony-stimulating factors and interleukin-1 beta did not affect microglial B7-2
      expression. Combined IFN gamma and lipopolysaccharide treatment very effectively
      upregulated the B7-2 gene expression and immunoreactivity in microglia, but not
      in astrocytes. In both glial cell types, expression of B7-1 was not induced by
      any of the above agents. Among known microglia/macrophage deactivators,
      interleukin-10, prostaglandin E2 and cAMP-elevating agents, but not transforming
      growth factor-beta 1 and interleukin-4, inhibited B7-2 transcripts and
      immunoreactivity in IFN gamma/LPS-stimulated microglia, thus suggesting possible
      paracrine and autocrine mechanisms for regulating the expression of this
      important T-cell costimulatory signal in the brain.

PMID- 9003247
TI  - Modulation of the alpha 2 macroglobulin receptor/low density lipoprotein receptor
      related protein by interferon-gamma in human astroglial cells.
AB  - Alpha 2 macroglobulin receptor/low density lipoprotein receptor-related protein
      (alpha 2 Mr/LRP) is a multi-functional cell surface receptor that has been
      implicated in important processes, such as atherogenesis, cellular migration,
      immune response and degenerative diseases. Its expression increases in human
      brain during Alzheimer's disease, tissue injury and neoplastic transformation. In
      the present paper we studied the regulation of alpha 2 Mr expression by
      interferon-gamma (IFN gamma) in human astrocytoma cell lines and in fetal
      astrocytes. Western blots demonstrated an increase of the alpha 2 Mr expression
      after 24 h of IFN gamma treatment. This effect paralleled the up-regulation of
      alpha 2 Mr mRNA, as detected by PCR. By prolonging incubation with IFN gamma, we
      observed a decrement of alpha 2 Mr in IFN gamma treated cells, both by western
      blot and cytometric analysis. Since in the same cells IFN gamma also up-regulates
      alpha 2 macroglobulin, this effect may be due to an augmented degradation of the
      receptor during its recycling.

PMID- 9003249
TI  - Therapy with antibody against leukocyte integrin VLA-4 (CD49d) is effective and
      safe in virus-facilitated experimental allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is facilitated in resistant BALB/c
      mice by intraperitoneal infection with an avirulent Semliki Forest virus (SFV
      A7). Viral infection increases the incidence of EAE from 15-30% to 60-90% and
      speeds up appearance of paralysis from 24 to 14 days. In this paper, we describe
      treatment of virus-facilitated EAE with monoclonal antibodies (mAbs) against
      leukocyte and/or endothelial cell adhesion molecules. Therapy with mAb against
      ICAM-1 (intercellular adhesion molecule-1) had a modest effect, but caused
      hemorrhagic brain and spinal cord lesions. Therapy with mAb against Mac-1 (alpha
      M beta 2-integrin) was well tolerated but had no effect. Therapy with mAb against
      VLA-4 (alpha 4 beta 1-integrin) was safe, diminished both clinical and
      histopathological signs of EAE, decreased induction of VCAM-1 (vascular cell
      adhesion molecule-1) on brain vessels and diminished infiltration of VLA-4+ cells
      into the brain. The amount of viral antigen in the brain was not altered. We
      conclude that facilitation of leukocyte entry into the brain is a major mechanism
      for viral facilitation of EAE in the BALB/c mouse, and that facilitation can be
      inhibited by anti-adhesion therapy. This may have implications for treatment of
      relapses triggered by viral infections in multiple sclerosis.

PMID- 9003250
TI  - Early fracture fixation may be deleterious after head injury.
AB  - OBJECTIVE: To determine the neurologic risks associated with early fracture
      fixation (FF) in multitrauma patients with head injuries. METHODS: We reviewed 33
      blunt trauma patients with significant closed head injuries (Abbreviated Injury
      Scale (AIS) score > or = 2) requiring operative FF. Nineteen patients underwent
      early FF defined as < or = 24 hours after injury, and 14 patients underwent late
      FF defined as > 24 hours after injury. The two groups were well matched in
      regards to age, 40.3 years (range, 8-88 years) versus 36.4 years (range, 8-75
      years), admission Glasgow Coma Scale score (12 +/- 4 vs. 11 +/- 5), and Injury
      Severity Score (25 +/- 10 vs. 27 +/- 12). Additionally, the groups had similar
      neurologic and orthopedic injury scores (AIS-CNS score = 3.3 +/- 0.9 vs. 3.1 +/-
      0.9, AIS-Ortho score = 3.0 +/- 0.9 vs. 2.9 +/- 0.7). Data were collected
      concerning the volume of fluid resuscitation, neurologic complications, and
      clinical outcomes. RESULTS: The early FF group received significantly more fluids
      in the first 48 hours (14.0 +/- 10.2 vs. 8.7 +/- 3.5 liters, p < 0.05). The early
      group trended towards a higher rate of intraoperative hypotension (systolic blood
      pressure < 90 mm Hg, 16% vs. 7%) and intraoperative hypoxia (O2-Saturation < or =
      90, 11% vs. 7%). The neurologic complication rate was similar in the two groups
      (early FF = 16% vs. late FF = 21%), but the average discharge Glasgow Coma Scale
      score was lower in the early group (13.5 +/- 3.7) when compared with the late FF
      patient group (15.0 +/- 0.0). CONCLUSIONS: Early FF leads to greater fluid
      administration in patients with head injuries. Hypoxemia and hypotension, risk
      factors for secondary brain injury, may contribute to a poor neurologic outcome
      after early fixation. Prospective studies evaluating the impact of the timing of
      FF on head injury are indicated.

PMID- 9003251
TI  - Defining the limits of survivorship after very severe head injury.
AB  - BACKGROUND: Reliable prediction of outcome after head injury is a daunting task.
      Although previous reports have highlighted the difficulties of determining
      outcome in the cohort of severe head injury Glasgow Coma Scale (GCS) score < or =
      8), we wondered within the very severely injured population (GCS score 3-5) if a
      simple combination of clinical parameters may be predictive of poor outcome.
      METHODS: All patients admitted to a Level 1 trauma center with a GCS score of 3
      to 5 from 1986 to 1991 inclusive (380 patients) were retrospectively reviewed and
      outcome a minimum of 6 months after injury was determined by chart review or
      telephone. RESULTS: Follow-up was accomplished in all but five patients (1.3%).
      Functional survival (nonvegetative) was correlated to admission GCS score,
      pupillary abnormalities, and age. As anticipated, overall functional survival was
      poor (12.5%), and even worse among those evidencing pupillary abnormalities
      (6.6%). Interestingly, there was an absence of survivors in the advanced age
      decades, with the oldest functional survivor of any GCS increasing in a stepwise
      fashion with increasing coma score. This translated into the oldest survivor of a
      GCS score of 3 being in their chronologic 30s, a score of 4 in their 40s, and a
      score of 5 in their 50s. Among patients older than these age decades, that is
      beyond this simple age/GCS cut-off (32.8% of cohort), there were no functional
      survivors (95% confidence interval 0, 2.4). CONCLUSIONS: Within the population of
      very severely head injured patients (GCS score 3-5), the simple combination of
      age and admission GCS score appears to predict accurately non-functional outcome
      in almost one third of patients. If confirmed at other centers, this may have
      wide-ranging implications regarding counseling of families, utilization of
      resources, and the design of head injury studies.

PMID- 9003253
TI  - Ender nailing for ipsilateral femoral shaft fractures after Austin-Moore
      hemiarthroplasty.
AB  - BACKGROUND: The management of ipsilateral femoral shaft fractures after
      hemiarthroplasty is controversial. METHODS: Fifteen patients (average age 82.4 +/
      8 years) with ipsilateral femoral shaft fractures after uncemented
      hemiarthroplasty were treated by closed reduction and Ender nailing. Under
      radiographic control, closed reduction was attempted. If not possible, cerclage
      of the shaft fracture was accomplished through a limited lateral approach. Ender
      nails were then inserted well past the tip of the stem of the prosthesis.
      RESULTS: There were a superficial wound infection and a deep vein thrombosis. At
      6 months, five patients had died, and backing out of the nails necessitated
      removal in one patient. At 1 year, nine patients were still alive. Of these,
      seven were able to walk with aids. At 2 years, seven patients were still alive
      and were walking with aids. Two patients presented shortening of more than 1.5 cm
      of the operated femur. After an average of 5 years, 11 patients were dead, two
      were still walking, and two were bedridden. CONCLUSIONS: The technique described
      is an option in the treatment of fractures of the ipsilateral femoral shaft after
      uncemented hemiarthroplasty.

PMID- 9003252
TI  - Fracture healing in tibia fractures with an associated vascular injury.
AB  - BACKGROUND: Tibial fractures with an associated vascular injury are a challenging
      management problem for the orthopedic and vascular surgeon. The effect of a
      concomitant vascular injury on fracture healing has not been specifically
      delineated previously. METHODS: We performed a retrospective review of 29
      fractures of the tibial shaft with an associated vascular injury in 28 patients.
      RESULTS: Overall there were 44 vessels injured (38 arterial and six venous). A
      total of six patients had an amputation performed; patients requiring amputation
      were significantly older than those without amputation. Fractures with an
      associated injury to the posterior tibial artery had a significantly higher
      nonunion rate and a greater number of weeks to union than fractures without this
      vascular injury. CONCLUSION: Outcomes of tibial fractures with an associated
      vascular injury are poorest in older patients (who are at increased risk of
      amputation) and those with an injury to the posterior tibial artery (who are at
      increased risk of delayed union and nonunion).

PMID- 9003254
TI  - Adrenal insufficiency in the surgical intensive care unit patient.
AB  - BACKGROUND: Adrenocortical dysfunction is unusual in the unselected critically
      ill patient. Case reports document a state of corticosteroid responsive
      vasopressor dependence, resembling the systemic inflammatory response syndrome.
      The exact incidence of this disorder is unknown. METHODS: We prospectively
      studied the incidence of adrenal insufficiency during a 9-month period in a
      surgical intensive care unit (ICU) population. Trauma, general surgery, urology,
      and gynecologic-oncology patients were included. Patients who met criteria were
      given a cosyntropin stimulation test. RESULTS: Overall, the incidence of adrenal
      insufficiency was 0.66%. In the subgroup of patients with greater than 14 days
      stay in the ICU, 6% were found to have adrenal insufficiency. In patients aged
      more than 55 years and with ICU stays of 14 days or greater, 11% were adrenally
      insufficient. CONCLUSIONS: Screening of critically ill patients for adrenal
      insufficiency, particularly those with prolonged ICU stay and age greater than 55
      years, is warranted.

PMID- 9003255
TI  - Cellular responses to surgical trauma, hemorrhage, and resuscitation with
      diaspirin cross-linked hemoglobin in rats.
AB  - BACKGROUND: Resuscitation with acellular oxygen carrier solutions offers the
      potential advantage of improved oxygen delivery compared with crystalloid
      solutions, but the detailed consequences of improved resuscitation have not been
      fully evaluated. This study evaluated local and systemic cellular effects of
      trauma, hemorrhage, and resuscitation in a model of hemorrhage and surgical
      trauma. METHODS: Rats with a 10 cm full-thickness incisional wound and a 15 mL/kg
      hemorrhage were either not resuscitated or resuscitated with blood or diaspirin
      cross-linked hemoglobin (DCLHb). Cellular proliferative responses were evaluated
      at 1.5, 6, 24, and 48 hours after wounding by labeling in vivo with 5-bromo-2'
      deoxyuridine. Plasma levels of interleukin-6, tumor necrosis factor-alpha, and
      interferon-gamma were measured by bioassay or enzyme-linked immunosorbent assay
      (ELISA). Bacterial translocation was measured by culturing liver homogenates.
      RESULTS: Trauma inhibited keratinocyte and hepatocyte proliferation at 1.5 and 6
      hours, and stimulated subsequent proliferation of keratinocytes and liver
      nonparenchymal cells. DCLHb stimulated wound keratinocyte proliferation,
      attenuated the inhibition of hepatocyte proliferation, eliminated bacterial
      translocation to the liver, protected the intestine from ischemic damage, and
      induced a rapid increase of interleukin-6 during the early phase of injury.
      CONCLUSIONS: Surgical trauma alone, or in combination with hemorrhage, modulated
      cell proliferation both in the wound and in the remote organs of intestine and
      liver. DCLHb enhanced wound healing and cell proliferation as well as, or better
      than, freshly drawn blood, which may be beneficial for trauma care.

PMID- 9003256
TI  - Effect of chronic cocaine administration on the hemodynamic response to acute
      hemorrhage in awake and anesthetized sheep.
AB  - BACKGROUND: Although Cocaine use is common in trauma victims, little is known
      about how cocaine affects the cardiovascular response to trauma and associated
      blood loss. This study determined the effect of chronic cocaine use on the
      cardiovascular response to hemorrhage in awake and anesthetized sheep. METHODS:
      The hemodynamic and acid-base responses to graded hemorrhage were determined in
      awake and anesthetized sheep at baseline and after 15 and 18 days of chronic
      cocaine exposure. RESULTS: Chronic cocaine exposure resulted in a moderate
      paradoxical bradycardic response to hemorrhage in awake sheep, but did not
      otherwise alter the hemodynamic response to hemorrhage. In anesthetized animals,
      cocaine exposure impaired the ability to maintain mean arterial pressure and
      cardiac output during hemorrhage, and resulted in a marked paradoxical
      bradycardic response to hemorrhage. CONCLUSIONS: Chronic cocaine exposure did not
      have an important effect on the cardiovascular response to hemorrhage in awake
      sheep. However, in anesthetized sheep, chronic cocaine exposure diminished the
      compensatory cardiovascular response to graded hemorrhage.

PMID- 9003257
TI  - Pancreatic trauma in children: mechanisms of injury.
AB  - BACKGROUND: Pancreatic trauma occurs in up to 10% of all cases of blunt pediatric
      trauma. Here we attempted to identify markers of pancreatic injury in children
      and to assess our current diagnostic approach to pancreatic injury. METHOD: We
      performed a retrospective chart review of all patients with a pancreatic injury
      admitted to a Level I pediatric trauma center between January of 1980 and
      September of 1994. RESULTS: In all, 26 children were included. All pancreatic
      injuries were due to blunt trauma. Handlebar injuries were the most common
      mechanism of injury and resulted in a unique pattern of isolated pancreatic
      trauma, often complicated by the development of a pseudocyst. Computed
      tomographic scans, performed with intravenous and oral contrast and done in the
      acute setting, were 85% sensitive for diagnosing a pancreatic injury.
      CONCLUSIONS: Double contrast computed tomographic scan is a more sensitive test
      than ultrasound in diagnosing pancreatic injury. The constellation of abdominal
      pain, an elevated serum amylase and a handlebar mechanism of injury warrants
      hospitalization and a double contrast abdominal computed tomographic scan.

PMID- 9003258
TI  - Long-term prevalence of impairments and disabilities after multiple trauma.
AB  - The prevalence of impairments and disabilities in activities of daily living
      (ADL), nonwork activities, and work were registered in a consecutive series (n =
      69) of subjects with severe injuries. At follow-up 3 years after trauma, residual
      impairments prevailed in 80%. Only a few (6%) were ADL-dependent. Seventy-six
      percent had lost at least one nonwork activity, while vocational disability
      caused by the trauma occurred in 19%. Cognitive impairment was significantly
      associated with vocational disability, while physical impairment and pain were
      significantly associated with nonwork disability. Other parameters that
      influenced vocational disability negatively were age and blue-collar employment
      status. Although overall changes in social network quantity and quality were
      small, significantly more subjects with cognitive impairment or vocational
      disability experienced a decline in the quality and quantity of their social
      network after trauma. Furthermore, 25% of the subjects reported an increase in
      feelings of loneliness after trauma. We recommend the design of individualized,
      multidisciplinary rehabilitation plans before discharge from departments of
      surgery.

PMID- 9003259
TI  - A chi-square automatic interaction detection (CHAID) analysis of factors
      determining trauma outcomes.
AB  - OBJECTIVE: Analysis of variables predictive of trauma outcome by the CHAID (chi
      square automatic interaction detection) statistical program. DESIGN:
      Retrospective analysis of a prospectively maintained trauma database. METHODS:
      The study group consisted of 607 primary ambulance retrievals to Royal Prince
      Alfred Hospital, Sydney, for the period of 6 fiscal years (1990-1996) with major
      injury (Injury Severity Score > 15). MAIN RESULTS: The overall mortality fell
      from 26.6 to 16% (chi 2 test = 14.7, p = 0.01) during the study period. The
      emergency room Glasgow Coma Scale (GCS) score (preresuscitation) was the
      strongest predictor of death or survival. CHAID segmented the study group into
      three categories based on GCS scores (?3?, ?4-12?, and ?13-15?), each with
      significantly different outcome predictability. The mortality rate in those with
      a GCS score of 3 (n = 89) was 67%. Systolic blood pressure was the strongest
      predictor of outcome in this subset. The mortality in those with GCS score of 4
      12 (n = 160) was 18%. Injury Severity Score was the strongest predictor in this
      subset. The mortality rate in those with GCS score of 13-15 was 5%. Age was the
      strongest predictor in this group. CONCLUSION: The CHAID-generated flowchart has
      proved useful in this pilot study to analyze the interrelation between variables
      predictive of outcome in an Australian urban trauma population.

PMID- 9003260
TI  - Predictive model to identify trauma patients with blood alcohol concentrations >
      or = 50 mg/dl.
AB  - OBJECTIVE: To develop a simple model for identification of trauma patients who
      are likely to have a blood alcohol concentration > or = 50 mg/dL (BAC + 50).
      METHODS: Demographic, clinical, and BAC data were collected from the clinical
      trauma registry and toxicology data base at a Level I trauma center. Logistic
      regression was used to analyze data from 11,206 patients to develop a predictive
      model, which was validated using a subsequent cohort of 3,523 patients. RESULTS:
      In the model development cohort, alcohol was detected in the blood of 3,180 BAC
      tested patients (28.7%), of whom 91.2% had a BAC + 50 status. Preliminary
      analysis revealed associations between a BAC + 50 status and sex, age, race,
      injury type (intentional vs. unintentional), and time of injury (night vs. day
      and weekend vs. weekday). A predictive model using four attributes (sex and
      injury type) identified patients at low, medium, and high risk for being BAC +
      50. The model was validated using the second group of patients. CONCLUSION:
      Injured patients with a high probability of being alcohol positive can be
      identified using a simple scoring system based on readily available demographic
      and clinical information.

PMID- 9003261
TI  - Dehydroepiandrosterone protects muscle flap microcirculatory hemodynamics from
      ischemia/reperfusion injury: an experimental in vivo study.
AB  - This study evaluated the potential for dehydroepiandrosterone (DHEA) to protect
      skeletal muscle from reperfusion injury using intravital microscopic observations
      of isolated rat cremaster muscle flaps. The flaps were subjected to warm ischemia
      followed by reperfusion in three groups of rats. In group 1 (control, n = 14),
      muscle flaps were subjected to 6 hours of ischemia and then evaluated after
      either 90 minutes (n = 8) or 24 hours (n = 6) of reperfusion. Group 2 animals
      (propylene glycol pretreatment, n = 8) were pretreated with a propylene glycol
      vehicle, then underwent 6 hours of ischemia and were evaluated after 90 minutes
      reperfusion. Group 3 animals (DHEA pretreatment, n = 12) were pretreated with
      DHEA dissolved in propylene glycol, subjected to 6 hours of ischemia, and then
      evaluated after either 90 minutes (n = 6) or 24 hours (n = 6) of reperfusion. Red
      blood cell velocity in the flap's main arteriole, functional capillary density,
      venular constriction index (the ratio of internal to external diameter of
      postcapillary venules), and microemboli formation were measured. Muscle samples
      were evaluated by electron microscopy. Control animals showed a 61% reduction in
      red blood cell velocity (p < 0.05) accompanied by a 69% reduction in functional
      capillary density (p < .05) acutely and total cessation of flow by 24 hours. No
      differences between control and propylene glycol treated animals were noted. In
      DHEA-pretreated animals, reflow occurred in 100% of the flaps, there was a
      temporary 39% reduction (p < 0.05) in functional capillary density, and all flaps
      remained viable at 24 hours. In this study, DHEA pretreatment markedly improved
      muscle flap microcirculatory hemodynamics and protected flaps against
      ischemia/reperfusion injury.

PMID- 9003262
TI  - Tracheobronchial cytology in inhalation injury.
AB  - The aim of this study is to establish whether tracheobronchial cytology is useful
      in the diagnosis of inhalation injury. Twenty patients diagnosed to have
      inhalation injury by existing clinical criteria and 20 control patients were
      admitted into the study. Bronchoscopy and brush biopsies were carried out. They
      were then scored using a Total Cellular Score and Differential Cellular Score.
      These were compared with clinical and bronchoscopic scores and respiratory
      outcome. The average Total Cellular Score of the patients with inhalation injury
      was 497.4 +/- 281.9 and that of the control patients was 1004.2 +/- 88.4. There
      was a strong correlation between clinical, bronchoscopic, and total cellular
      scores. The Differential Cellular Score showed a left shift in patients with
      inhalation injury. This study shows that tracheobronchial cytology is a useful
      adjunct in diagnosing and assessing the severity of inhalation injury.
      Furthermore, our results suggest that it may be superior to current methods in
      predicting respiratory outcome.

PMID- 9003263
TI  - Hemopneumothorax missed by auscultation in penetrating chest injury.
AB  - OBJECTIVE: To determine the frequency and extent of hemothorax, pneumothorax, and
      hemopneumothorax missed by auscultation in penetrating chest injury. DESIGN: A
      retrospective chart and chest radiograph review. MATERIALS AND METHODS: One
      hundred and eighteen patients suffering penetrating chest injuries during 1993
      were studied. A missed auscultation was defined as a patient with normal breath
      sounds but shown by chest radiograph to have a hemothorax, pneumothorax, or
      hemopneumothorax. The amount of hemothorax was recorded after chest tube
      placement or at thoracotomy. The degree of pneumothorax was determined by Rhea's
      method. RESULTS: Seventy-one patients (60%) had a hemothorax, pneumothorax, or
      hemopneumothorax. Auscultation to detect hemothorax, pneumothorax, or
      hemopneumothorax had a sensitivity of 58%, a specificity of 98%, and a positive
      predictive value of 98%. Thirty of 71 patients (42%) were found to have pleural
      space blood or air missed by auscultation. Twelve patients (41%) had a
      hemopneumothorax, 11 patients (36%) had hemothorax, and seven patients (23%) had
      pneumothorax. Auscultation missed hemothorax up to 600 mL, pneumothorax up to
      28%, and hemopneumothorax up to 800 mL and 28%. CONCLUSION: Hemopneumothorax and
      hemothorax are the conditions most likely to be missed by auscultation,
      especially in patients with gunshot wounds. Auscultation has a high positive
      predictive value because it indicates injury with a fair degree of certainty;
      however, a negative auscultation does not rule out injury.

PMID- 9003265
TI  - Posttrauma thromboembolism prophylaxis.
AB  - PURPOSE: The need to study methods of thromboembolism prophylaxis in high-risk
      trauma patients is well established. The purpose of this study was to evaluate
      the feasibility of a proposed study design, including current methods of
      prophylaxis, performance of a risk assessment profile scale, and the use of
      serial color-flow duplex studies in detecting deep venous thrombosis (DVT).
      METHODS: Patients were enrolled into the study, stratified as to their ability to
      receive anticoagulation and randomized to low-dose unfractionated heparin, low
      molecular weight heparin, pneumatic compression devices, or foot pumps with or
      without vena caval filters. Serial ultrasound scans were performed at designated
      intervals for 4 weeks. Pulmonary angiograms were obtained for clinical signs or
      symptoms of pulmonary embolism. RESULTS: Fifty-three patients, 32 male and 21
      female patients with a mean age of 44 years, completed the study. The incidence
      of DVT was 43% (23 of 53 patients) and significantly higher in older patients.
      There were no pulmonary embolisms. Color-flow duplex proved to be a sensitive
      method for detecting both proximal and distal thrombi. The risk assessment
      profile for thromboembolism (RAPT) scale identified a group of patients with a
      high incidence of DVT. However, the occurrence of DVT was not correlated with the
      magnitude of the RAPT score. CONCLUSION: The ability to identify a population
      with a high incidence of thromboembolism by using the RAPT score to detect
      asymptomatic DVT, and the suggested advantage of low molecular weight heparin,
      all support the need for an appropriately powered randomized clinical trial.

PMID- 9003264
TI  - Statewide, population-based, time-series analysis of the frequency and outcome of
      pulmonary embolus in 318,554 trauma patients.
AB  - The low occurrence, nonspecific signs and symptoms, and high rate of associated
      morbidity and mortality of pulmonary embolus (PE) create major problems in the
      prevention, diagnosis, and treatment of PE. The purpose of this study was to
      analyze the frequency and outcome of PE in an entire state's trauma population
      using a large, population-based, hospital discharge data base. With the inclusion
      of an entire population, the reported incidence, high risk groups of patients,
      and specific risk factors regarding PE were assessed. A multivariate, logistic
      regression model was created from the data to determine predictive power of
      selected risk factors in patients at risk. METHODS: The data source was a
      statewide, hospital discharge data base that includes data on all hospitalized
      patients for all of the hospitals in North Carolina. Data were available from
      1988 to 1993. Using primary discharge diagnosis and nine additional ICD-9 coded
      diagnoses from the discharge abstract, patients were selected by presence of
      diagnostic codes for traumatic injury (800-959.9) and PE (415.1). Statistical
      analysis was performed using univariate and multivariate analysis to determine
      significant risk factors and to create a candidate model for the prediction of
      risk in the study population. RESULTS: Of 318,554 patients, 952 (0.30%) had a
      recorded diagnosis of PE. The mortality rate for patients with PE (26%) was 10
      times higher than the mortality rate in patients without PE (2.6%). In evaluating
      specific risk factors, age was a significant predictor of the risk of PE: 0.05%
      for patients under age 55 and 0.7% in those 55 years and over. The rate of PE,
      0.3%, was low for the entire study population, but was highest in patients with
      injuries of the extremities, 0.53%. Increasing Injury Severity Score and
      Abbreviated Injury Scale score for determined body systems were also found to
      correlate with an increasing risk of PE. Over the course of the study, the
      incidence of PE among patients discharged from non-trauma centers showed a
      significant decrease. There was also a decrease in the mortality in non-trauma
      centers for PE. This finding cannot be due to coding changes coincident with the
      advent of diagnosis related groups because it would be associated with more
      vigorous combing of charts for diagnoses? It may well be that the use of
      prophylactic measures in injured patients initially used at trauma centers was
      adopted by the physicians at non-trauma centers over this time with the resultant
      decline in PE and associated mortality. From the univariate linear regression
      models, a logistic regression model was created that confirmed age as the most
      significant risk factor, followed by Injury Severity Score and Abbreviated Injury
      Scale score for soft tissue, extremity, and chest. The calculated area under the
      receiver operator characteristic curve was 0.72. CONCLUSION: Using a large,
      population-based data base, we were able to determine the reported incidence of
      PE among trauma patients and establish specific risk factors. The reported
      incidence of PE in this population is low, 0.30%. The mortality among those with
      PE, however, is significant at 26%. In this study, age, Injury Severity Score,
      and injury to specific body regions (soft tissue, extremity, chest) were
      associated with an increased risk of PE. The investigation of prophylaxis of PE
      and the general management of injured patients may be influenced by the overall
      low reported frequency of PE and the specific high risk populations described in
      this study. In light of the low incidence of PE in patients without specific risk
      factors, prophylactic interventions cannot be routinely recommended unless their
      benefits clearly outweigh their risks.

PMID- 9003266
TI  - Deletion of the p53 gene in a patient with aggressive burn scar carcinoma.
AB  - BACKGROUND: Aggressive squamous cell carcinoma (SCC) is known to occur in scars
      that develop after a burn injury, especially in the underdeveloped areas of the
      world where care is lacking. Because most SCC are associated with abnormalities
      in tumor suppressor genes, particularly p53, we postulated that similar
      mechanisms may underlie the development of burn-associated SCC. METHODS: We
      analyzed tissue DNA from a patient who died from an aggressive SCC in a burn scar
      for evidence of p53 gene abnormalities by polymerase chain reaction and
      immunohistochemical staining for p53 protein. RESULTS: Using polymerase chain
      reaction, the p53 gene could not be detected in DNA from the patient's cancer.
      The p53 protein was also undetectable by immunohistochemical staining.
      CONCLUSION: These studies indicate that there was a homozygous deletion of the
      p53 gene in this burn-related carcinoma. Further studies of other patients may
      lead to new understanding of this cancer, explain in part the usual aggressive
      behavior, and lead to new methods of prevention and treatment.

PMID- 9003267
TI  - Combined differential lung ventilation and inhaled nitric oxide therapy in the
      management of unilateral pulmonary contusion.
AB  - Unilateral pulmonary contusion after blunt thoracic trauma can prove to be a
      devastating injury. Regional disturbances in blood flow and alveolar ventilation
      can significantly alter pulmonary function. We present a case report of
      unilateral pulmonary contusion that resulted in significant pulmonary
      dysfunction. This patient was successfully managed with multimodality therapy
      consisting of differential lung ventilation and inhaled nitric oxide. The effect
      of nitric oxide applied to the "normal" lung, the "injured" lung, and both lungs
      is described. The use of inhaled nitric oxide was associated with an increase in
      oxygenation when applied to the normal or both lungs. The use of nitric oxide in
      conjunction with differential lung ventilation appeared to offer benefit in this
      patient with severe unilateral pulmonary contusion.

PMID- 9003268
TI  - Traumatic pneumatosis cystoides intestinalis with portal venous air embolism.

PMID- 9003269
TI  - Traumatic intrapericardial diaphragmatic hernia diagnosed by echocardiography.
AB  - Emergency Department echocardiography revealed an intrapericardial hollow viscus
      in an 80-year-old auto crash victim. This proved to be stomach herniated through
      a ruptured diaphragm. Echocardiography and ultrasonography are very valuable
      diagnostic procedures currently available to the trauma surgeon to rule out
      diaphragmatic injury early in the trauma room.

PMID- 9003270
TI  - Bilateral gluteal compartment syndrome.
AB  - Gluteal compartment syndrome is uncommon but potentially devastating. Bilateral
      gluteal compartment syndrome occurs far more infrequently, with only three
      previous cases reported to date. This report reviews a case of bilateral gluteal
      compartment syndrome, the relevant anatomy of the gluteal region, and the
      etiology, pathophysiology, diagnosis, and treatment of this phenomenon.

PMID- 9003271
TI  - Gunshot wounds of the internal carotid artery at the skull base: management with
      vein bypass grafts and a review of the literature.
AB  - BACKGROUND: Penetrating trauma to the skull base and distal cervical internal
      carotid artery (ICA) can result in occlusion or pseudoaneurysm formation. The
      appropriate management strategy for these rare lesions is controversial and
      includes observation, anticoagulation, carotid ligation, balloon occlusion, or
      revascularization. METHODS: We present the management and outcomes of four
      consecutive patients, two with pseudoaneurysms and two with acute occlusions,
      after injury to the distal cervical/petrous ICA from gunshot wounds. Preoperative
      assessment determined intracranial collateral flow patterns and the patency of
      the distal portion of the petrous ICA. RESULTS: Two patients underwent cervical
      to-petrous ICA vein bypass grafts without neurologic complications. Both grafts
      remain patent without evidence of emboli at 2 years and 3 months, respectively.
      Both of the conservatively managed patients died, one from a massive cerebral
      infarction and the other from intracerebral hemorrhage. CONCLUSIONS: These cases
      underscore the need for an aggressive approach to the assessment and management
      of patients with penetrating vascular skull-base injuries. Although the optimal
      treatment of remains controversial, when the goal is exclusion of the injured
      portion of the carotid artery and revascularization, the cervical to petrous ICA
      vein bypass graft is a valuable management option that can reduce the potential
      morbidity and mortality from acute ischemic or delayed embolic or hemorrhagic
      complications, provide immediate restoration of high flow, and allow good
      surgical access with minimal risk to intracranial structures.

PMID- 9003272
TI  - Isolated common iliac artery occlusion secondary to atherosclerotic plaque
      rupture from blunt abdominal trauma: case report and review of the literature.
AB  - Traumatic isolated common iliac artery occlusion is unusual. Only rare cases of
      common iliac arterial injuries resulting from blunt abdominal trauma have been
      reported, and most of them were attributed to the seat-belt syndrome and
      associated with visceral organ perforation or pelvic fracture. We reported an
      unusual isolated common iliac artery occlusion secondary to atherosclerotic
      plaque rupture from blunt abdominal compressive trauma without other visceral
      injury. This case presented with acute limb ischemia and paralysis that was
      successfully treated by thromboendarterectomy. The symptoms and signs, surgical
      modalities, and associated injuries were reported and the literature was also
      reviewed.

PMID- 9003273
TI  - Thoracic aortic rupture during vigorous exercise.

PMID- 9003274
TI  - Blunt traumatic avulsion of the inferior vena cava: case report.

PMID- 9003275
TI  - Usefulness of color Doppler sonography in a growing skull fracture: case report.
AB  - A case of an 11-month-old infant with a growing skull fracture is described. The
      patient was admitted with disturbance of consciousness and left hemiparesis after
      a severe head injury. A pulsating protrusion appeared over the fracture line 1
      month later. Color Doppler sonography revealed cerebral herniation and cystic
      lesion via the bony defect, together with an intracranial arterial flow pattern
      detected in the extracranial space. Color Doppler sonography was very useful in
      the diagnosis of growing skull fracture and in the evaluation of the intracranial
      state, including hemodynamics in this case. Successful surgical treatment was
      performed on the basis of sonographic data and the patient was discharged 3
      months later without motor deficits.

PMID- 9003276
TI  - Locked-in syndrome resulting from cervical spine gunshot wound.
AB  - A patient sustained a cervical spine gunshot wound resulting in immediate
      quadriplegia and obstruction of both vertebral arteries. After an 8-hour delay,
      basilar artery thrombosis occurred and resulted in locked-in syndrome. Bilateral
      occlusion of the vertebral arteries after penetrating cervical trauma has not
      been reported previously. The incidence and treatment of traumatic basilar
      thrombosis and locked-in syndrome is reviewed. Rapid diagnosis of ascending
      thrombosis and prompt treatment with hyperdynamics and anticoagulation may
      improve outcome.

PMID- 9003277
TI  - Alterations in leukocyte adhesion molecule expression after burn injury.

PMID- 9003279
TI  - Radiographic cervical spine evaluation in the alert asymptomatic blunt trauma
      victim: much ado about nothing?

PMID- 9003278
TI  - Shotgun slug injuries: case report and literature review.

PMID- 9003280
TI  - Cloning of the polyketide synthase gene atX from Aspergillus terreus and its
      identification as the 6-methylsalicylic acid synthase gene by heterologous
      expression.
AB  - Southern blot analysis of genomic DNAs of several fungi that produce polyketide
      compounds with the 6-methylsalicylic acid synthase (MSAS) gene of Penicillium
      patulum as a probe indicated the presence of an MSAS-homologous gene in the (+)
      geodin-producing strain IMI 16,043 of Aspergillus terreus. The gene, designated
      atX was cloned from an A. terreus genomic DNA library and 7588 bp of the gene
      together with its flanking regions were sequenced to reveal the presence of a 5.5
      kb open reading frame coding for a protein of 1800 amino acids with 190 kDa
      molecular mass. The presence of a short (70 bp) intron near the N-terminus of the
      atX gene was predicted that contains the canonical GT and AG dinucleotides at its
      5'- and 3'-splicing junctions. The predicted ATX polypeptide showed high homology
      with P. patulum MSAS along the whole sequence. On the other hand, slight homology
      was detected only around the beta-ketoacyl synthase regions of Aspergillus
      nidulans wA, PKSST and Colletotrichum lagenarium PKS1. No transcription of atX
      was observed throughout the culture period by Northern blotting analysis. To
      identify the function of the polypeptide encoded by the atX gene, its coding
      region was introduced into the fungal expression vector pTAex3 under the control
      of the amyB promoter. The constructed expression plasmid was introduced into A.
      nidulans. The transformant produced significant amounts of 6-methylsalicylic
      acid, the structure of which was identified by physicochemical analysis. This
      result unambiguously demonstrated that the atX gene codes for MSAS of A. terreus.

PMID- 9003281
TI  - Mapping of the entomocidal fragment of Spodoptera-specific Bacillus thuringiensis
      toxin CryIC.
AB  - Insecticidal CryI protoxins of Bacillus thuringiensis are activated by
      proteolysis in the midgut of insects. A conservation of proteolytic cleavage
      sites in the CryI proteins facilitates the expression of active toxins in
      transgenic plants to obtain protection from various insects. However, the
      engineering of CryIC toxins has, thus far, failed to yield applicable resistance
      to armyworms of Spodoptera species representing common insect pests worldwide. To
      improve the production of recombinant CryIC toxins, we established a CryIC
      consensus sequence by comparative analysis of three cryIC genes and tested the
      stability and protease sensitivity of truncated CryIC toxins in Escherichia coli
      and in vitro. In contrast to previous data, the boundaries of trypsin-resistant
      CryIC core toxin were mapped to amino acid residues I28 and R627. Proteolysis of
      the truncated CryIC proteins showed that Spodoptera midgut proteases may further
      shorten the C-terminus of CryIC toxin to residue A615. However, C-terminal
      truncation of CryIC to residue L614, and a mutation causing amino acid
      replacement I610T, abolished the insecticidal activity of CryIC toxin to S.
      littoralis larvae, as well as its resistance to trypsin and Spodoptera midgut
      proteases. Because no CryIC toxin carrying a proteolytically processed N-terminus
      could be stably expressed in bacteria, our data indicate that, in contrast to
      other CryI proteins, an entomocidal fragment located between amino acid positions
      1 and 627 is required for stable production of recombinant CryIC toxins.

PMID- 9003282
TI  - Genes from the medicinal leech (Hirudo medicinalis) coding for unusual enzymes
      that specifically cleave endo-epsilon (gamma-Glu)-Lys isopeptide bonds and help
      to dissolve blood clots.
AB  - We previously detected in salivary gland secretions of the medicinal leech
      (Hirudo medicinalis) a novel enzymatic activity, endo-epsilon(gamma-Glu)-Lys
      isopeptidase, which cleaves isopeptide bonds formed by transglutaminase (Factor
      XIIIa) between glutamine gamma-carboxamide and the epsilon-amino group of lysine.
      Such isopeptide bonds, either within or between protein polypeptide chains are
      formed in many biological processes. However, before we started our work no
      enzymes were known to be capable of specifically splitting isopeptide bonds in
      proteins. The isopeptidase activity we detected was specific for isopeptide
      bonds. The enzyme was termed destabilase. Here we report the first purification
      of destabilase, part of its amino acid sequence isolation and sequencing of two
      related cDNAs derived from the gene family that encodes destabilase proteins, and
      the detection of isopeptidase activity encoded by one of these cDNAs cloned in a
      baculovirus expression vector. The deduced mature protein products of these cDNAs
      contain 115 and 116 amino acid residues, including 14 highly conserved Cys
      residues, and are formed from precursors containing specific leader peptides. No
      homologous sequences were found in public databases.

PMID- 9003284
TI  - Chromosome landing at the Arabidopsis TORNADO1 locus using an AFLP-based
      strategy.
AB  - The Arabidopsis tornado1 (trn1) mutation causes severe dwarfism combined with
      twisted growth of all organs. We present a chromosome landing strategy, using
      amplified restriction fragment length polymorphism (AFLP) marker technology, for
      the isolation of the TRN1 gene. The recessive trn1 mutation was identified in a
      C24 transgenic line and is located 5 cM from a T-DNA insertion. We mapped the
      TRN1 locus to the bottom half of chromosome 5 relative to visible and restriction
      fragment length polymorphism (RFLP) markers. Recombinant classes within a 3-cM
      region around TRN1 were used to build a high-resolution map in this region, using
      the AFLP technique. Approximately 300 primer combinations have been used to test
      about 26,000 fragments for polymorphisms. Seventeen of these AFLP markers were
      identified in the 3-cM region around TRN1. These markers were mapped within this
      region using individual recombinants. Four of these AFLP markers co-segregate
      with TRN1 whereas one maps at one recombinant below TRN1. We isolated and cloned
      three of these AFLP markers. These markers identified two yeast artificial
      chromosome (YAC) clones, containing the RFLP marker above and the AFLP marker
      below TRN1, demonstrating that these YACs span the TRN1 locus and that chromosome
      landing has been achieved, using an AFLP-based strategy.

PMID- 9003283
TI  - The gene fl(2)d is needed for the sex-specific splicing of transformer pre-mRNA
      but not for double-sex pre-mRNA in Drosophila melanogaster.
AB  - In Drosophila melanogaster, regulation of the sex determination genes throughout
      development occurs by sex-specific splicing of their products. The first gene is
      Sex-lethal(Sxl). The downstream target of Sxl is the gene transformer (tra): the
      Sxl protein controls the female-specific splicing of the Tra pre-mRNA. The
      downstream target of the gene tra is the gene double-sex (dsx): the Tra protein
      of females, controls the female-specific splicing of the Dsx pre-mRNA. We have
      identified a gene, female-lethal-2-d fl(2) d, whose function is required for the
      female-specific splicing of Sxl pre-mRNA. In this report we analyze whether the
      gene fl(2)d is also required for the sex-specific splicing of both Tra and Dsx
      pre-mRNAs. We found that the Sxl protein is not sufficient for the female
      specific splicing of Tra pre-mRNA, the fl(2)d function also being necessary. This
      gene, however, is not required for the female-specific splicing of Dsx pre-mRNA.

PMID- 9003285
TI  - The localized melting of mini-F origin by the combined action of the mini-F
      initiator protein (RepE) and HU and DnaA of Escherichia coli.
AB  - Replication of mini-F plasmids requires the initiator protein RepE, which binds
      specifically to four iterons within the origin (ori2), as well as some host
      factors that are involved in chromosomal DNA replication. To understand the role
      of host factors and RepE in the early steps of mini-F DNA replication, we
      examined the effects of RepE and the Escherichia coli proteins DnaA and HU on the
      localized melting of ori2 DNA in a purified in vitro system. We found that the
      binding of RepE to an iteron causes a 50 degrees bend at or around the site of
      binding. RepE and HU exhibited synergistic effects on the localized melting
      within the ori2 region, as detected by sensitivity to the single-strand specific
      P1 endonuclease. This opening of duplex DNA occurred around the 13mer of ori2,
      whose sequence closely resembles the set of 13mers found in the chromosomal
      origin oriC. Further addition of DnaA to the reaction mixture increased the
      efficiency of melting and appeared to extend melting to the adjacent AT-rich
      region. Moreover, DNA melting with appreciably higher efficiencies was observed
      with mutant forms of RepE that were previously shown to be hyperactive both in
      DNA binding in vitro and in initiator activity in vivo. We propose that the
      binding of RepE to four iterons of ori2 causes bending at the sites of RepE
      binding and, with the assistance of HU, induces a localized melting in the 13mer
      region. The addition of DnaA extends melting to the AT-rich region, which could
      then serve as the entry site for the DnaB-DnaA complex, much as has been
      documented for oriC dependent replication.

PMID- 9003286
TI  - The transposable element Tan1 of Aspergillus niger var. awamori, a new member of
      the Fot1 family.
AB  - Aspergillus niger var. awamori has transposable elements that we refer to as
      Vader and Tan1 (transposon A. niger). Vader was identified by screening unstable
      nitrate reductase (niaD) mutants for insertions. Four of the isolated niaD
      mutants were shown to contain a small insertion element. This 437 bp insertion
      element, Vader, is flanked by 44 bp inverted repeats (IR) and is present in
      approximately 15 copies in the genomes of two A. niger strains examined. A
      synthetic 44 bp oligomer of the inverted repeat of Vader has now been used to
      clone, via the polymerase chain reaction, a 2.3 kb Tan1 element. The Tan1 element
      has also been isolated from a partial genomic library. Tan1 is present as a
      single copy in A. niger var. awamori. The Tan1 element has a unique organization:
      IR-ORF-IR-IR-Vader-IR. The single open reading frame (ORF) (1668 bp) encodes a
      putative transposase homologous to Fusarium oxysporum Fot1 and Magnaporthe grisea
      Pot2. Immediately 3' to the second inverted repeat, which bounds the transposase,
      is a copy of the AT-rich Vader element. We hypothesize that at some stage the
      independent Vader element, although inactive by itself, arose from Tan1,
      resulting in current strains with only one copy of Tan1 providing transposase
      activity and numerous mobile copies of Vader dispersed in the genome.

PMID- 9003287
TI  - Use of competitive PCR to assay copy number of repetitive elements in banana.
AB  - Banana is one of the most important subtropical fruit crops. Genetic improvement
      by traditional breeding strategies is difficult and better knowledge of genomic
      structure is needed. Repeated sequences are powerful markers for genetic
      fingerprinting. The method proposed here to determine the copy number of nuclear
      repetitive elements is based on competitive reverse transcription-polymerase
      chain reaction and can also be used for quantifying cytosolic sequences. The
      reliability of this method was investigated on crude preparations of total DNA.
      Variations due to the heterogeneity of crude DNA extracts showed that a single
      locus reference is needed for accurate quantification. A mapped microsatellite
      locus was used to normalize copy number measurements. Copy number assay of
      repetitive elements using this method clearly distinguishes between the two
      banana subspecies investigated: Musa acuminata spp. banskii and M. acuminata spp.
      malaccensis. Two repetitive sequence families, pMaCIR1115 and pA9-26, were
      assayed that cover up to 1% of the M. acuminata genome. Their copy number varied
      up to six fold between the two subspecies. Furthermore, sequence quantification
      showed that mitochondrial genomes are present in crude leaf-extracted banana DNA
      at up to 40 copies per cell.

PMID- 9003288
TI  - Dictyostelium discoideum cobB mutants show reduced heavy metal accumulation
      associated with gene amplification.
AB  - Wild-type Dictyostelium discoideum cells growing on non-toxic levels of nickel
      chloride or cobaltous chloride accumulate 2-3.5 times as much nickel and at least
      1.5 times as much cobalt as cobB mutants. The cobB trait is dominant, confers
      unstable cobalt and nickel resistance and is correlated with the presence of up
      to 50 copies of a linear extrachromosomal DNA, approximately 100 kb in length,
      derived from linkage group III. Independent cobB mutants can be obtained by
      selection on medium containing either cobalt or nickel. The amplified DNA can be
      transferred to wild-type strains by electroporation. Strains with mutations at a
      second cobalt resistance locus, cobA, accumulate the same amount of cobalt, but
      more nickel than wild-type strains. Our results are consistent with the cobA
      mutant phenotype being due to internal sequestration of cobalt, and the cobB
      mutant phenotype being due to reduced net uptake of cobalt and nickel. Energy
      dependent nickel export was detectable in wild-type and cobB mutant strains but
      its role in heavy metal resistance has not yet been proved.

PMID- 9003289
TI  - Comparative analysis of expression of the SalI restriction-modification system in
      Escherichia coli and Streptomyces.
AB  - The salIR and salIM genes encode the endonuclease and methyltransferase
      components of the SalI restriction-modification system from Streptomyces albus G.
      Expression of the salI genes in Escherichia coli was investigated and major
      differences with Streptomyces were found. In E. coli there is no detectable
      expression of the salI R gene due to inactivity of the sal-pR promoter region. In
      the natural host of the system this region directs transcription of the salI
      genes as a bicistronic message. In contrast to salIR, salIM is transcribed in the
      heterologous host from a promoter within the salI DNA. Since sal-pR is not
      active, the gene cannot be expressed as part of the salI operon. It is probably
      transcribed from sal-pM, a promoter internal to the operon which allows
      independent expression of the modification gene in Streptomyces. Replacement of
      sal-pR by the strong pLac promoter allows expression of salIR in E. coli and
      enhances expression of salIM. The resulting strain produces about 10 times more
      endonuclease than a Streptomyces clone containing the SalI system under the
      control of sal-pR.

PMID- 9003290
TI  - Complementation of a yeast top2ts mutation by a cDNA encoding rat DNA
      topoisomerase II alpha.
AB  - A series of yeast expression plasmids which comprise segments of the cDNA
      sequences encoding rat topo II alpha have been constructed. The transcription of
      these constructs is under the control of the yeast GAL1 promoter. Galactose
      dependent expression of the cloned rat topo II alpha cDNA complemented a yeast
      top2ts mutation, as well as a deletion mutation at the yeast TOP2 locus.
      Truncation of 12 N-terminal amino acids and/or 158 C-terminal amino acids of rat
      topo II alpha had no effect on its ability functionally to substitute for top2ts.
      Moreover, a cDNA construct with mutated putative leucine zipper domain (amino
      acids 993-1013) retained the complementation activity. These observations suggest
      that transformants capable of conditional topo II alpha expression can be
      exploited as a useful model system for studies on the structure-function
      relationships of wild-type and mutated topo II alpha, as well as the interplay of
      potential antitumor drugs with the enzyme.

PMID- 9003291
TI  - Stress-induced rearrangement of Fusarium retrotransposon sequences.
AB  - Rearrangement of fusarium oxysporum retrotransposon skippy was induced by growth
      in the presence of potassium chlorate. Three fungal strains, one sensitive to
      chlorate (Co60) and two resistant to chlorate and deficient for nitrate reductase
      (Co65 and Co94), were studied by Southern analysis of their genomic DNA.
      Polymorphism was detected in their hybridization banding pattern, relative to the
      wild type grown in the absence of chlorate, using various enzymes with or without
      restriction sites within the retrotransposon. Results were consistent with the
      assumption that three different events had occurred in strain Co60: genomic
      amplification of skippy yielding tandem arrays of the element, generation of new
      skippy sequences, and deletion of skippy sequences. Amplification of Co60 genomic
      DNA using the polymerase chain reaction and divergent primers derived from the
      retrotransposon generated a new band, corresponding to one long terminal repeat
      plus flanking sequences, that was not present in the wild-type strain. Molecular
      analysis of nitrate reductase-deficient mutants showed that generation and
      deletion of skippy sequences, but not genomic amplification in tandem repeats,
      had occurred in their genomes.

PMID- 9003292
TI  - Effects of mutations in genes for proteins involved in disulphide bond formation
      in the periplasm on the activities of anaerobically induced electron transfer
      chains in Escherichia coli K12.
AB  - The assembly of anaerobically induced electron transfer chains in Escherichia
      coli strains defective in periplasmic disulphide bond formation was investigated.
      Strains deficient in DsbA, DsbB or DipZ (DsbD) were unable to catalyse formate
      dependent nitrite reduction (Nrf activity) or synthesize any of the known c-type
      cytochromes. The Nrf+ activity and cytochrome c content of mutants defective in
      DsbC, DsbE or DsbF were similar to those of the parental, wild-type strain.
      Neither DsbC expressed from a multicopy plasmid nor a second mutation in dipZ
      (dsbD) was able to compensate for a dsbA mutation by restoring nitrite reductase
      activity and cytochrome c synthesis. In contrast, only the dsbB and dipZ (dsbD)
      strains were defective in periplasmic nitrate reductase activity, suggesting that
      DsbB might fulfil an additional role in anaerobic electron transport. Mutants
      defective in dipZ (dsbD) were only slightly more sensitive to Cu++ ions at
      concentrations above 5 mM than the parental strain, but strains defective in
      DsbA, DsbB, DsbC, DsbE or DsbF were unaffected. These results are consistent with
      our earlier proposals that DsbA, DsbB and DipZ (DsbD) are part of the same
      pathway for ensuring that haem groups are attached to the correct pairs of
      cysteine residues of apocytochromes c in the E. coli periplasm. However, neither
      DsbE nor DsbF are essential for the reduction of DipZ (DsbD).

PMID- 9003293
TI  - Characterization of a promoter mutation in the CYP3 gene of Saccharomyces
      cerevisiae which cancels regulation by Cyp1p (Hap1p) without affecting its
      binding site.
AB  - Cyp1p (Hap1p) activates, among others, the two structural genes, CYC1 and CYP3
      (CYC7) which encode isocytochromes c in Saccharomyces cerevisiae. This activation
      is believed to occur through the binding of the protein to the dissimilar
      upstream activation sequences (UASs), UAS1 and UAS', present upstream of CYC1 and
      CYP3, respectively. In this paper, we describe a novel promoter mutation, CYP3-5,
      which results from a 39-bp deletion located about 160 bp upstream of the well
      characterized CYP3 UAS. This deletion includes a sequence identical to the 3'
      moiety of the CYC1 UAS1. Strikingly, a sequence identical to the 5' part of the
      CYC1 UAS1 is also present 60 bp downstream of the 3' half in the wild-type gene,
      suggesting that a spatial organization of the promoter might lead to the
      reconstitution in vivo of an active UAS1-like sequence. Interestingly, we find
      that in the presence of the CYP3-5 mutation, which disrupts this potential UAS1,
      the CYP-UAS' complex is importantly diminished and the transcription of CYP3 is
      insensitive to the wild-type CYP1-activating protein.

PMID- 9003294
TI  - Superfamily of alpha-galactosidase MEL genes of the Saccharomyces sensu stricto
      species complex.
AB  - In order to study the molecular evolution of the yeasts grouped in the
      Saccharomyces sensu stricto species complex by analysis of the MEL gene family,
      we have cloned and sequenced two new species-specific MEL genes from
      Saccharomyces yeasts: S. paradoxus (MELp) and a Japanese Saccharomyces sp.
      (MELj). The clones were identified by sequence homology to the S. cerevisiae MEL1
      gene. Both clones revealed an ORF of 1413 bp coding for a protein of 471 amino
      acids. The deduced molecular weights of the alpha-galactosidase enzymes were
      52,767 for MELp and 52,378 for MELj. The nucleotide sequences of the MELp (EMBL
      accession no. X95505) and the MELj (EMBL accession no. X95506) genes showed 74.7%
      identity. The degree of identity of MELp to the MEL1 gene was 76.8% and to the S.
      pastorianus MELx gene, 75.7%. The MELj coding sequence was 75.1% identical to the
      MEL1 gene and 80.7% to the MELx gene. The data suggest that MEL1, MELj, MELp, and
      MELx genes are species-specific MEL genes. The strains studied each have only one
      MEL locus. The MELp gene is located on the S. paradoxus equivalent of S.
      cerevisiae chromosome X; the MELj gene was on the chromosome that comigrates with
      the S. cerevisiae chromosome VII/XV doublet and hybridizes to the S. cerevisiae
      chromosome XV marker HIS3.

PMID- 9003295
TI  - Isolation of novel pre-mRNA splicing mutants of Schizosaccharomyces pombe.
AB  - New prp (pre-mRNA processing) mutants of the fission yeast Schizosaccharomyces
      pombe were isolated from a bank of 700 mutants that were either temperature
      sensitive (ts-) or cold sensitive (cs-) for growth. The bank was screened by
      Northern blot analysis with probes complementary to S. pombe U6 small nuclear RNA
      (sn RNA), the gene for which has a splicesomal (mRNA-type) intron. We identified
      12 prp mutants that accumulated the U6 snRNA precursor at the nonpermissive
      temperature. All such mutants were also found to have defects in an early step of
      TFIID pre-mRNA splicing at the nonpermissive temperature. Complementation
      analyses showed that seven of the mutants belong to six new complementation
      groups designated as prp8 and prp10-prp14, whereas the five other mutants were
      classified into the known complementation groups prp1, prp2 and prp3.
      Interestingly, some of the isolated prp mutants produced elongated cells at the
      nonpermissive temperature, which is a phenotype typical of cell division cycle
      (cdc) mutants. Based on these findings, we propose that some of the wild-type
      products from these prp+ genes play important roles in the cellular processes of
      pre-mRNA splicing and cell cycle progression.

PMID- 9003296
TI  - 5-Azacytidine treatment of the fission yeast leads to cytotoxicity and cell cycle
      arrest.
AB  - A fission yeast gene which shares considerable sequence homology with cytosine
      specific DNA methyltransferases has recently been identified. This discovery has
      led us to investigate the effects of the treatment of fission yeast with the
      nucleoside analogue 5-azacytidine (5-azaC). 5-AzaC is known to inhibit cytosine
      methylation as a result of the formation of stable covalent complexes between DNA
      (cytosine-5) methyltransferases (C5 Mtases) and 5-azaC containing DNA. Here we
      demonstrate that 5-azaC treatment of Schizosaccharomyces pombe leads to
      reversible cell cycle arrest at the G2/M transition. This reversible arrest is
      dependent on the cell cycle checkpoint mechanisms which act to prevent the onset
      of mitosis in the presence of either damaged or unreplicated DNA. Treatment of S.
      pombe cell division cycle and checkpoint mutants indicates that 5-azaC causes DNA
      damage and is likely to inhibit a late stage in DNA replication. The data show
      that viability in the presence of the drug requires both the DNA damage and the
      replication checkpoint pathways to be functional. 5-AzaC also elicits a
      transcriptional response which is associated with DNA damage and the inhibition
      of DNA replication in fission yeast, and this response is absent in cells
      carrying G2 checkpoint mutations. The implications of these observations for both
      the use of 5-azaC in cancer chemotherapy and the existence of cytosine
      methylation in fission yeast are discussed.

PMID- 9003297
TI  - Cdc20, a beta-transducin homologue, links RAD9-mediated G2/M checkpoint control
      to mitosis in Saccharomyces cerevisiae.
AB  - In the budding yeast Saccharomyces cerevisiae, the DNA damage-induced G2 arrest
      requires the checkpoint control genes RAD9, RAD17, RAD24, MEC1, MEC2 and MEC3.
      These genes also prevent entry into mitosis of a temperature-sensitive mutant,
      cdc13, that accumulates chromosome damage at 37 degrees C. Here we show that a
      cdc13 mutant overexpressing Cdc20, a beta-transducin homologue, no longer arrests
      in G2 at the restrictive temperature but instead undergoes nuclear division,
      exits mitosis and enters a subsequent division cycle, which suggests that the DNA
      damage-induced G2/M checkpoint control is not functional in these cells. This is
      consistent with our observation that overexpression of CDC20 in wild-type cells
      results in increased sensitivity to UV irradiation. Overproduction of Cdc20 does
      not influence the arrest phenotype of the cdc mutants whose cell cycle block is
      independent of RAD9-mediated checkpoint control. Therefore, we suggest that the
      DNA damage-induced checkpoint controls prevent mitosis by inhibiting the nuclear
      division pathway requiring CDC20 function.

PMID- 9003298
TI  - Genetic interaction of DED1 encoding a putative ATP-dependent RNA helicase with
      SRM1 encoding a mammalian RCC1 homolog in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae temperature-sensitive mutants srm1-1, mtr1-2 and
      prp20-1 carry alleles of a gene encoding a homolog of mammalian RCC1. In order to
      identify a protein interacting with RCC1, a series of suppressors of the srm1-1
      mutation were isolated as cold-sensitive mutants and one of the mutants,
      designated ded1-21, was found to be defective in the DED1 gene. The double
      mutant, srm1-1 ded1-21, could grow at 35 degrees C, but not at 37 degrees C. A
      revertant of srm1-1 ded1-21 that became able to grow at 37 degrees C acquired
      another mutation in the SRM1 gene, indicating the tight relationship between SRM1
      and DED1. In all the rcc1- strains examined, the amount of mutated SRM1 proteins
      was reduced or not detectable at the nonpermissive temperature. While mutated
      SRM1 protein was stabilized in all of the rcc1- strains by the ded1-21 mutation,
      the ded1-21 mutation suppressed both srm1-1 and mtr1-2, but not the prp20-1
      mutation, contrary to the previous finding that overproduction of the S.
      cerevisiae Ran homolog GSP1 suppresses prp20-1, but not srm1-1 or mtr1-2.

PMID- 9003299
TI  - Degenerative spermatocyte, a novel gene encoding a transmembrane protein required
      for the initiation of meiosis in Drosophila spermatogenesis.
AB  - We have identified a novel Drosophila gene, degenerative spermatocyte (des), that
      may be required for the initiation of meiosis in spermatogenesis. In des mutant
      testes, the primary spermatocytes become mature in size but degenerate without
      initiating meiotic chromosome condensation in their nuclei. We have mapped the
      locus of the des gene at 26A on the left arm of the second chromosome, and
      identified two related, differentially spliced transcripts (des-1, des-2) from
      the locus. The genomic DNA fragment encoding both transcripts is able to rescue
      the des phenotype when introduced into mutant flies. The expression of the des-1
      transcript is significantly suppressed in the des mutant testes, whereas
      expression of the des-2 transcript is undetectable in both wild-type and mutant
      testes, indicating that the des-1 transcript encodes the des function in
      spermatogenesis. The des-1 transcript is selectively expressed in primary
      spermatocytes during normal spermatogenesis. The nucleotide sequence of the des-1
      transcript predicts that it encodes a novel transmembrane protein. These results
      raise the possibility that the des gene product may be required for interactions
      between primary spermatocytes and surrounding somatic cells.

PMID- 9003301
TI  - Illegitimate integration of single-stranded DNA in Saccharomyces cerevisiae.
AB  - We studied illegitimate recombination by transforming yeast with a single
      stranded (ss) non-replicative plasmid. Plasmid pCW12, containing the ARG4 gene,
      was used for transformation of yeast strains deleted for the ARG4, either in
      native (circular) form or after linearization within the vector sequence by the
      restriction enzyme ScaI. Both circular and linearized ss plasmids were shown to
      be much more efficient in illegitimate integration than their double-stranded
      (ds) counterparts and more than two-thirds of the transformants analysed
      contained multiple tandem integrations of the plasmid. Pulsed-field gel
      electrophoresis of genomic DNA revealed significant changes in the karyotype of
      some transformants. Plasmid DNA was frequently detected on more than one
      chromosome and on mitotically unstable, autonomously replicating elements. Our
      results show that the introduction of nonhomologous ss DNA into yeast cells can
      lead to different types of alterations in the yeast genome.

PMID- 9003300
TI  - Characterization, sequence and mode of replication of plasmid pNB2 from the
      thermophilic bacterium Clostridium thermosaccharolyticum.
AB  - The 1882-bp nucleotide sequence of the cryptic plasmid pNB2 isolated from the
      thermophilic bacterium Clostridium thermosaccharolyticum was determined. pNB2 DNA
      has very low GC content (27%) and may serve as a model for studying the modes of
      maintenance and replication of AT-rich DNA under conditions of thermophilic
      growth. The plasmid sequence revealed three open reading frames (ORFs) which
      would encode polypeptides of 289, 68 and 59 amino acids, respectively, and these
      proteins were synthesized in E. coli extracts primed with the plasmid. We found
      that the product of ORF289 may be initiated at the non-ATG start codon, TTG, and
      has similarities with the conserved motifs of Rep proteins encoded by rolling
      circle (RC) plasmids of the pC194/pUB110 family. Southern hybridization analysis
      of lysates of C. thermosaccharolyticum cells harboring pNB2 revealed single
      stranded intermediates, suggesting that this plasmid is able to replicate in
      clostridial cells via the RC mechanism. The most significant similarities are
      found between pNB2 Rep protein and the Rep proteins of three RC plasmids of the
      pC194 family (pTB913, pBC1 and pST1) isolated from thermophilic bacteria.
      Comparative analysis of these Rep proteins showed that despite the significant
      level of divergence, these Rep proteins share a high degree of similarity in the
      regions of five well-known conserved domains of RC Rep proteins and fall into two
      groups in accordance with the similarities found in their active sites.

PMID- 9003302
TI  - Accumulation of mitochondrial DNA deletions in myotubes cultured from muscles of
      patients with mitochondrial myopathies.
AB  - Myoblast cultures were established from muscle biopsies of two patients harboring
      heteroplasmic mitochondrial (mt) DNA deletions. The accumulation kinetics of the
      deleted mtDNA was followed during myoblast to myotube differentiation. The
      percentage of deleted mtDNA was determined by quantitative PCR in myoblasts,
      myotubes, and muscle biopsies. The deleted form accounted for 65% of the mtDNA
      present in a muscle biopsy from a patient harboring a 5.6-kb deletion. The
      percentage of deleted mtDNA was 1.2% in myoblasts and increased progressively
      after differentiation, up to 12% at 21 days after the commitment time. In a
      second patient harboring a 2.8-kb deletion, the percentage of deleted mtDNA
      increased much more slowly: from 0.07% in myoblasts to 0.21% after 22 days of
      differentiation, as compared with 45% in the muscle biopsy. Thus, a three- and
      ten-fold increase, respectively, in the fraction of deleted mtDNA occurred during
      the differentiation of myoblasts to myotubes from the two patients. The faster
      accumulation of deleted mtDNA int he first patient's cells was linked to an
      earlier myoblast to myotube differentiation, suggesting that the level of deleted
      mtDNA is inversely related to the rate of cell proliferation.

PMID- 9003303
TI  - delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase is a rate limiting
      enzyme for penicillin production in Aspergillus nidulans.
AB  - The acvA gene from Aspergillus nidulans encoding delta-(L-alpha-aminoadipyl)-L
      cysteinyl-D-valine (ACV) synthetase was overexpressed by replacing the wild-type
      acvA promoter with the ethanol dehydrogenase promoter, alcAp, from A. nidulans.
      The expression level of alcAp was determined using a strain in which the reporter
      gene, lacZ, is under the control of alcAp, and was found to be up to 100 times
      greater than that from the acvA promoter when induced in fermentation conditions.
      Penicillin yields were found to increase by as much as 30-fold when the acvA gene
      was overexpressed. Glucose, which strongly represses transcription from alcAp,
      also repressed penicillin biosynthesis in the overexpression strain. These
      results prove that ACV synthetase is a rate limiting enzyme for penicillin
      production in A. nidulans.

PMID- 9003304
TI  - Down regulation of cAMP production by cAMP receptor protein in Escherichia coli:
      an assessment of the contributions of transcriptional and posttranscriptional
      control of adenylate cyclase.
AB  - Escherichia coli cells that are deficient in the cAMP receptor protein (CRP)
      overproduce cAMP. We and others have previously found that transcription of the
      adenylate cyclase gene (cya) is negatively regulated by the CRP-cAMP complex.
      Here, we have investigated the contribution of this transcriptional regulation to
      the control of cAMP levels. Several variants of the cya gene have been
      constructed and characterized with respect to their expression and their ability
      to produce cAMP. Overproduction of cAMP in a crp- background was reduced from 200
      fold to 50-fold when transcriptional regulation by CRP-cAMP was eliminated by
      replacing the cya promoter with the constitutive bla promoter. When the C
      terminal 48 amino acids of adenylate cyclase were deleted without changing the
      promoter, the degree of overproduction of cAMP was reduced to 4-fold. Finally,
      the increase in cAMP level observed in crp- cells was almost completely abolished
      when the truncated cyclase was expressed from the bla promoter. We conclude that
      transcriptional regulation of cya does indeed play a role in the down-regulation
      of cAMP production by CRP, although the major regulation is exerted at the
      posttranscriptional level. The C-terminal region comprising the last 48 amino
      acids of cyclase is responsible for the posttranscriptional regulation. A simple
      new method for the determination of cAMP is also described.

PMID- 9003305
TI  - Functional promoter elements common to ribosomal protein and ribosomal RNA genes
      in Neurospora crassa.
AB  - The promoter sequences of a cytoplasmic ribosomal protein gene (crp-2) of
      Neurospora crassa were identified using promoter deletion and substitution
      mutants. A gene-targeting strategy was used to assay the mutants in vivo. The
      promoter architecture of crp-2 is complex and is more similar to that of
      ribosomal protein genes in mouse than in Saccharomyces cerevisiae. Six regions
      were identified as important for transcription. These included two elements, a CG
      repeat and a Dde box, that are conserved in most other promoters of N. crassa
      ribosomal protein genes and have also been demonstrated as being required for
      transcription from the 40 S rRNA promoter by RNA polymerase I in vitro. The CG
      repeats located at -73 to -66 and between -189 and -154 were functionally
      redundant and increased transcription efficiency by 10- to 15- fold. The Dde
      boxes located at -153 to -147 and at -95 to -83 contributed 2-fold and 5-fold to
      transcription efficiency, respectively. An unidentified element between -254 and 
      190 contributed 2-fold, while a pyrimidine-rich region between -85 and -66
      influenced the start point of transcription.

PMID- 9003306
TI  - A general system for generating unlabelled gene replacements in bacterial
      chromosomes.
AB  - A general system is described that facilitates gene replacements such that the
      recombinant strains are not labelled with antibiotic resistance genes. The method
      is based on the conditional replication of derivatives of the lactococcal plasmid
      pWV01, which lacks the repA gene encoding the replication initiation protein.
      Replacement vectors can be constructed in and isolated from gram-positive and
      gram-negative helper strains that provide RepA in trans. Cointegrate formation of
      the integration vectors with the chromosome of the target strain is selected by
      antibiotic resistance. Resolution of the cointegrate structure is identified in
      the second step of the procedure by the loss of the lacZ reporter gene present in
      the delivery vector. The second recombination event results either in gene
      replacement or in restoration of the original copy of the gene. As no antibiotic
      resistance marker is present in the genome of the mutant the system can be used
      to introduce multiple mutations in one strain. A feasibility study was performed
      using Lactococcus lactis and Bacillus subtilis as model organisms. The results
      indicate that the method should be applicable to any non-essential gene in
      numerous bacterial species.

PMID- 9003308
TI  - Inheritance patterns of new genetic markers and occurrence of spontaneous
      mosaicism in the monogenic blowfly Chrysomya rufifacies (Diptera:Calliphoridae).
AB  - Four new genetic markers for Chrysomya rufifacies, a fly with maternal sex
      determination, were characterized. The markers include one body colour mutant,
      black body (bl), and three eye colour mutants, brown eye (br), apricot eye (ap),
      and red eye (wr). Two of the latter, br and wr, turn out to be sex linked, the
      others behave as autosomal genes belonging to different linkage groups. wr is a
      hypomorphic and w an apomorphic mutation of the white gene, w/w is epistatic to
      br/br and to ap/ap. A preliminary genetic linkage map with the sex realizer F'/f
      and the loci br and w residing in homomorphic sex chromosomes is established.
      Evidence is presented that crossing over is absent in the male sex. The possible
      causes of the spontaneous appearance of mosaics for eye colour observed among
      individuals heterozygous for recessive genes are discussed.

PMID- 9003307
TI  - The physical relationship of barley chromosome 5 (1H) to the linkage groups of
      rice chromosomes 5 and 10.
AB  - Using a recently developed polymerase chain reaction (PCR)-mediated approach for
      physical mapping of single-copy DNA sequences on microisolated chromosomes of
      barley, sequence-tagged sites of DNA probes that reveal restriction fragment
      length polymorphisms (RFLP) localized on the linkage maps of rice chromosomes 5
      and 10 were allocated to cytologically defined regions of barley chromosome 5
      (1H). The rice map of linkage group 5, of about 135 cM in size, falls into two
      separate parts, which are related to the distal portions of both the short and
      long arms of the barley chromosome. The markers on the rice map of chromosome 5
      were found to be located within regions of the barley chromosome which show high
      recombination rates. The map of rice chromosome 10, of about 75 cM in size, on
      the other hand, is related to an interstitial segment of the long arm of
      chromosome 5 (1H) which is highly suppressed in recombination activity. For
      positional cloning of genes of this homoeologous region from the barley genome,
      the small rice genome will probably prove to be a useful tool. No markers located
      on rice chromosomes were detected within the pericentric Giemsa-positive
      heterochromatin of the barley chromosome, indicating that these barley-specific
      sequences form a block which separates the linkage segments conserved in rice. By
      our estimate approximately half of the barley-specific sequences of chromosome 5
      (1H) show a dispersed distribution, while the other half separates the conserved
      linkage segments.

PMID- 9003309
TI  - Gene expression from replicating plasmids in Aspergillus nidulans.
AB  - Plasmids bearing the AMA1 replicator from Aspergillus nidulans are capable of
      extrachromosomal replication in this fungus as well as in other species.
      Synthetic plasmids bearing the moderately expressed argB gene and the highly
      expressed, inducible beta-galactosidase gene (bgaS) were introduced into fungal
      cells. Expression of both genes was monitored by Northern hybridization. It was
      demonstrated that transcription of bgaS is induced and repressed normally,
      irrespective of whether the gene is integrated into the chromosome or maintained
      on an extrachromosomal supercoiled plasmid. Transcription of the strongly
      expressed bgaS gene stimulates transcription of the argB gene located on the same
      replicating plasmid irrespective of orientation. This effect also occurs with
      chromosomally integrated vectors, but to a lesser extent. Episomal vectors are
      present in 10 copies per nucleus, and the expression level of the argB gene is
      approximately proportional to copy number. However, the amount of mRNA
      transcribed from the highly expressed bgaS gene on the multi-copy replicating
      plasmid does not exceed that from single-copy integrants. High levels of
      expression of the plasmid-borne gene do not affect plasmid mitotic stability or
      copy number.

PMID- 9003310
TI  - A novel repetitive sequence associated with the centromeric regions of
      Arabidopsis thaliana chromosomes.
AB  - The middle repetitive fraction of the Arabidopsis genome has been relatively
      poorly characterized. We describe here a novel repetitive sequence cloned in the
      plasmid mi167, and present in approximately 90 copies in the genome of
      Arabidopsis thaliana ecotype Columbia. Hybridization analysis to physically
      mapped YAC clones representing Arabidopsis chromosome 4 revealed four mi167
      hybridizing loci, all clustered near the centromere. No other loci were detected
      on YAC clones covering chromosome 4. In situ hybridisation experiments to
      Arabidopsis chromosome spreads showed that mi167-hybridizing sequences are
      clustered at the centromeric heterochromatin of all five chromosomes; on two
      chromosomes the hybridization appeared to be localised on one arm. Additional
      mi167-hybridizing loci were detected, one of which was adjacent to a non
      centromeric, heterochromatic region. This work supports the idea that the
      majority of middle repetitive DNA in the Arabidopsis genome is clustered. It also
      adds to our understanding of the organization of the centromere of Arabidopsis
      chromosome 4.

PMID- 9003311
TI  - Molecular analysis of the Rhodobacter capsulatus B10 porin (porCa) gene;
      purification and biochemical characterisation of the porin protein.
AB  - The pore-forming outer-membrane protein from Rhodobacter (R.) capsulatus (wild
      type B10 strain) was isolated and purified under non-denaturing conditions. The
      monomer unit of the isolated porin has a molecular mass of about 28 kDa, as
      judged by SDS-PAGE, whereas the native protein migrates at 75 kDa. This suggests
      that the native porin from R. capsulatus B10 exists in a trimeric form. The N
      terminal amino acid sequence was used to design an oligonucleotide which was
      utilised to screen a pBluescript library containing EcoRI fragments of R.
      capsulatus B10 DNA. A 5.3-kb DNA fragment, which included the entire structural
      porin gene (named porCa) and its flanking regions, was identified. A 945-bp open
      reading frame, coding for a mature protein of 295 amino acid residues (molecular
      mass 30,586 Da) plus a presequence of 20 amino acids, was found. The directly
      determined sequence of the amino-terminus and of four tryptic peptides of the
      purified porin matched perfectly with the deduced amino acid sequence. Northern
      blot analysis showed that the porin gene encodes an RNA transcript of 1050
      nucleotides. In addition, there is no differential response in terms of either
      the size or abundance of the mRNA under different environmental conditions.
      Primer extension experiments confirmed a putative promoter upstream of the porin
      gene; and localised the RNA transcription start site 73 bp upstream of the ATG
      start codon, which is close to the putative promoter (-10/-35). As shown using a
      plasmid-borne porin-lacZ gene fusion, [in R. capsulatus] expression of the lacZ
      gene under the control of the porCa promoter is not regulated under the two
      different environmental conditions tested. The promoter of the porin gene was
      localised within 305 bp upstream of the ATG start codon. A model of the 3-D
      structure of porin B10 was deduced by comparative modelling with the R.
      capsulatus 37b4 and Rhodopseudomonas blastica porin crystallographic structures
      using the ProMod program on the Swiss-Model protein modelling e-mail Server.
      Analysis of the B10 sequence and comparison of a model of the B10 porin structure
      with the crystallographic structure of porin from the capsuleless strain 37B4 has
      revealed some important differences at the level of the protein surface, the pore
      and the putative ligand binding site.

PMID- 9003312
TI  - PHH1, a novel gene from Arabidopsis thaliana that encodes a protein similar to
      plant blue-light photoreceptors and microbial photolyases.
AB  - A cDNA from Arabidopsis thaliana similar to microbial photolyase genes, and
      designated AT-PHH1, was isolated using a photolyase-like cDNA from Sinapsis alba
      (SA-PHR1) as a probe. Multiple isolations yielded only PHH1 cDNAs, and a few blue
      light-receptor CRY1 (HY4) cDNAs (also similar to microbial photolyase genes),
      suggesting the absence of any other highly similar Arabidopsis genes. The AT-PHH1
      and SA-PHR1 cDNA sequences predict 89% identity at the protein level, except for
      an AT-PHH1 C-terminal extension (111 amino acids), also not seen in microbial
      photolyases. AT-PHH1 and CRY1 show less similarity (54% p4erein identity),
      including respective C-terminal extensions that are themselves mostly dissimilar.
      Analysis of fifteen AT-PHH1 genomic isolates reveals a single gene, with three
      introns in the coding sequence and one in the 5'-untranslated leader. Full-length
      AT-PHH1, and both AT-PHH1 and AT-PHH1 delta C-513 (truncated to be approximately
      the size of microbial photolyase genes) cDNAs, were overexpressed, respectively,
      in yeast and Escherichia coli mutants hypersensitive to ultraviolet light. The
      absence of significant effects on resistance suggests either that any putative AT
      PHH1 DNA repair activity requires cofactors/chromophores not present in yeast or
      E. coli, or that AT-PHH1 encodes a blue-light/ultraviolet-A receptor rather than
      a DNA repair protein.

PMID- 9003313
TI  - The KEULE gene is involved in cytokinesis in Arabidopsis.
AB  - We present evidence to show that the KEULE gene of Arabidopsis is involved in
      cytokinesis. Mutant keule embryos have large multinucleate cells with gapped or
      incomplete cross walls, as well as cell wall stubs that are very similar to those
      observed upon caffeine inhibition of cytokinesis in plants. These defects are
      observed in all populations of dividing cells in the mutant, including calli, but
      less frequently in mature cells. Cell division appears to be slowed down, and the
      planes of cell division are often misoriented. In late embryos and seedlings,
      cross-wall formation usually appears complete, suggesting that the requirement
      for KEULE during cytokinesis is not absolute. Nonetheless, keule mutants die as
      seedlings with large polyploid cells. The bloated surface layer of keule
      seedlings does not uniformly behave like wild-type epidermis, and patches of this
      layer assume characteristics of the underlying ground tissue. The cytokinesis
      defect of keule mutants may influence aspects of cellular differentiation.

PMID- 9003314
TI  - A meiosis-specific protein kinase, Ime2, is required for the correct timing of
      DNA replication and for spore formation in yeast meiosis.
AB  - In this report we study the regulation of premeiotic DNA synthesis in
      Saccharomyces cerevisiae. DNA replication was monitored by fluorescence-activated
      cell sorting analysis and by analyzing the pattern of expression of the DNA
      polymerase alpha-primase complex. Wild-type cells and cells lacking one of the
      two principal regulators of meiosis, Ime1 and Ime2, were compared. We show that
      premeiotic DNA synthesis does not occur in ime1 delta diploids, but does occur in
      ime2 delta diploids with an 8-9 h delay. At late meiotic times, ime2 delta
      diploids exhibit an additional round of DNA synthesis. Furthermore, we show that
      in wild-type cells the B-subunit of DNA polymerase alpha is phosphorylated during
      premeiotic DNA synthesis, a phenomenon that has previously been reported for the
      mitotic cell cycle. Moreover, the catalytic subunit and the B-subunit of DNA
      polymerase alpha are specifically degraded during spore formation.
      Phosphorylation of the B-subunit does not occur in ime1 delta diploids, but does
      occur in ime2 delta diploids with an 8-9 h delay. In addition, we show that Ime2
      is not absolutely required for commitment to meiotic recombination, spindle
      formation and nuclear division, although it is required for spore formation.

PMID- 9003315
TI  - Entamoeba histolytica: gene linkage groups and relevant features of its
      karyotype.
AB  - We identified some gene linkage groups in Entamoeba histolytica using a 4-M urea
      improved transversal alternating field electrophoresis (TAFE) method. Complex
      rosette-structured DNA molecules were found trapped along the gel lanes,
      explaining the fuzziness of the patterns. Using several episomal probes,
      including 16 S, 5.8 S, and 25 S ribosomal (r)Dna genes, an autonomous replication
      sequence (ARS), and EhVR1, we identified a complete ribosomal episome linkage
      group (CELG) at the 1.2-Mb position. Three other incomplete groups were found:
      IELG-1, formed by EhVR1, 16 S, 5.8 S, and 25 S genes; IELG-2 formed by EhVR1, 16
      S and 25 S; and IELG-3 formed only by 5.8 S. Ehadh3, Ehpfo, and Ehredox genes
      migrated at the 1.8-Mb position, forming the non-ribosomal linkage group, NRLG
      1.8, while the Ehenl-1 gene migrated at 1.6 Mb forming the NRLG-1.6 group. Ehhk
      was located at 1.2, 0.8, and 0.17 Mb in three different groups: NRLG-1.2, IELG-3
      0.8, and NRLG-0.17. Putative lineal chromosomes were also identified using an
      heterologous telomeric probe. By in situ hybridization experiments, the rDNA and
      Ehhk genes were located in both nucleus and cytoplasm, while the Ehpfo and
      Ehredox genes were found mainly in the nucleus. We propose a model hypothezising
      that the 16 S and 25 S genes are in a linear molecule, duplicated in two inverted
      repeats, which may be looped out of the linear DNA to form an episome probably
      lacking or not the 5.8 S sequence, which could be added later by recombination.

PMID- 9003316
TI  - Increase in synthesis and stability of sigma 32 on treatment with inhibitors of
      DNA gyrase in Escherichia coli.
AB  - We report here that in Escherichia coli, the anti-bacterial agent nalidixic acid
      induces transient stabilization and increased synthesis of sigma 32, accompanied
      by the induction of heat shock proteins (Dnak and GroEL proteins). The induction
      of heat shock proteins, increased synthesis of sigma 32, and stabilization of
      sigma 32 observed on treatment of wild-type cells with nalidixic acid were not
      observed in a nalA26 mutant, a strain that is resistant to nalidixic acid as the
      result of a mutation in the gyrA gene. Not only oxolinic acid, but also
      novobiocin, whose targets are the A and B subunits of DNA gyrase, respectively,
      also induced stabilization and increased synthesis of sigma 32. Thus, inhibition
      of the activity of DNA gyrase may cause stabilization and increased synthesis of
      sigma 32, resulting in turn in induction of heat shock proteins.

PMID- 9003318
TI  - scsB, a cDNA encoding the hydrogenosomal beta subunit of succinyl-CoA synthetase
      from the anaerobic fungus Neocallimastix frontalis.
AB  - A clone containing a Neocallimastix frontalis cDNA assumed to encode the beta
      subunit of succinyl-CoA synthetase (SCSB) was identified by sequence homology
      with prokaryotic and eukaryotic counter-parts. An open reading frame of 1311 bp
      was found. The deduced 437 amino acid sequence showed a high degree of identity
      to the beta-succinyl-CoA synthetase of Escherichia coli (46%), the mitochondrial
      beta-succinyl-CoA synthetase from pig (48%) and the hydrogenosomal beta-succinyl
      CoA synthetase from Trichomonas vaginalis (49%). The G + C content of the
      succinyl-CoA synthetase coding sequence (43.8%) was considerably higher than that
      of the 5' (14.8%) and 3' (13.3%) non-translated flanking sequences, as has been
      observed for other genes from N. frontalis. The codon usage pattern was biased,
      with only 34 codons used and a strong preference for a pyrimidine (T) in the
      third positions of the codons. The coding sequence of the beta-succinyl-CoA
      synthetase cDNA was cloned in an E. coli expression vector encoding a 6(His) tag.
      The recombinant protein was purified by affinity binding and used to produce
      polyclonal antibodies. The anti-succinyl-CoA synthetase serum recognized a 45 kDa
      protein from a N. frontalis fraction enriched for hydrogenosomes and similar
      polypeptides in two related anaerobic fungi, Piromyces rhizinflata (45 kDa) and
      Caecomyces communis (47 kDa). Immunocytochemical experiments suggest that
      succinyl-CoA synthetase is located in the hydrogenosomal matrix. Staining for SCS
      activity in native electrophoretic gels revealed a band with an apparent
      molecular weight of approximately 330 kDa. The C-terminus of the succinyl-CoA
      synthetase sequence was devoid of the typical targeting signals identified so far
      in microbody proteins, indicating that N. frontalis uses a different signal for
      sorting SCSB into hydrogenosomes. Based on comparisons with other proteins we
      propose a putative N-terminal targeting signal for succinyl-CoA synthetase of N.
      frontalis that shows some of the features of mitochondrial targeting sequences.

PMID- 9003317
TI  - Functional analysis of the cellobiohydrolase I promoter of the filamentous fungus
      Trichoderma reesei.
AB  - Functional analysis of the cellulase promoter cbh1 of the filamentous fungus
      Trichoderma reesei was carried out using the Escherichia coli lacZ gene as a
      reporter. An assay based on cultivation on solid medium in microtiter plates was
      developed that allows rapid and reliable semiquantitative analysis of beta
      galactosidase expression of a large number of transformants. A series of
      deletions and specifically designed alterations were made covering 2.2 kb of the
      cbh1 promoter. Removal of sequences upstream of nucleotide -500 in relation to
      the initiator ATG abolished glucose repression. Mutation of a single
      hexanucleotide sequence 5'GTGGGG at nucleotide -720 was sufficient for
      derepression. This site is similar to the binding sites of the glucose repressors
      MIG1 of Saccharomyces cerevisiae and CREA/CREI of filamentous fungi. Removal of
      the glucose repressor site did not affect sophorose induction. Sophorose
      induction of the promoter was retained even in deletion derivatives lacking
      sequences upstream of position -161, which retained about 70 bp upstream of the
      transcription start point and only 30 bp upstream of the TATA box.

PMID- 9003319
TI  - Prt1, an unusual retrotransposon-like sequence in the fungus Phycomyces
      blakesleeanus.
AB  - This work reports the isolation and structural characterization of Prt1, a 4.7 kb
      retrotransposon-like sequence from the filamentous fungus Phycomyces
      blakesleeanus. Two open reading frames are found within Prt1. The first shows no
      similarity with known genes. The second encodes peptide stretches similar to the
      reverse transcriptase and RNaseH domains of the Ty3/gypsy family of LTR
      retrotransposons. Prt1 lacks long terminal repeats, having instead short (54 bp)
      terminal inverted repeats. No target site duplication has been found. A single
      copy of Prt1 was detected in the genome of P. blakesleeanus. Adjacent to this
      sole copy of Prt1, a cluster of various short sequence repeats, both direct and
      inverted, is found. These sequences, which are reminiscent of defective, non
      retroviral transposable elements, are also represented in other regions of the P.
      blakesleeanus genome.

PMID- 9003320
TI  - Reciprocal regulation of delta 1-pyrroline-5-carboxylate synthetase and proline
      dehydrogenase genes controls proline levels during and after osmotic stress in
      plants.
AB  - Plants generally accumulate free proline under osmotic stress conditions. Upon
      removal of the osmotic stress, the proline levels return to normal. In order to
      understand the mechanisms involved in regulating the levels of proline, we cloned
      and characterized a proline dehydrogenase (PDH) cDNA from Arabidopsis thaliana
      (AtPDH). The 1745 bp cDNA contains a major open reading frame encoding a peptide
      of 499 amino acids. The deduced amino acid sequence has high homology with both
      Saccharomyces cerevisiae and Drosophila melanogaster proline oxidases and
      contains a putative mitochondrial targeting sequence. When expressed in yeast,
      the AtPDH cDNA complemented a yeast put1 mutation and exhibited proline oxidase
      activity. We also determined the free proline contents and the delta 1-pyrroline
      5-carboxylate synthetase (P5CS) and PDH mRNA levels under different osmotic
      stress and recovery conditions. The results demonstrated that the removal of free
      proline during the recovery from salinity or dehydration stress involves an
      induction of the PDH gene while the activity of P5CS declines. The reciprocal
      regulation of P5CS and PDH genes appears to be a key mechanism in the control of
      the levels of proline during and after osmotic stress. The PDH gene was also
      significantly induced by exogenously applied proline. The induction of PDH by
      proline, however, was inhibited by salt stress.

PMID- 9003321
TI  - Isolation of a carbon source-regulated gene from Ustilago maydis.
AB  - We have isolated a carbon source-regulated gene from the phytopathogenic fungus
      Ustilago maydis by use of a promoter-probe vector. This gene, called crg1, is
      strongly induced by L-arabinose and efficiently repressed by D-glucose and D
      xylose. The predicted 36.5-kDa mature crg1 gene product lacks similarity to known
      proteins but is likely to be secreted. Sequences required for regulated
      expression of a reporter gene are contained within a 3.6-kb fragment upstream of
      the crg1 gene. The promoter of crg1 fulfils requirements for an efficient
      controllable gene expression system in U. maydis

PMID- 9003322
TI  - Characterization of tryptophan synthase alpha subunit mutants of Arabidopsis
      thaliana.
AB  - Three mutations in the Arabidopsis thaliana gene encoding the alpha subunit of
      tryptophan synthase were isolated by selection for resistance to 5
      methylanthranilate or 5-fluoroindole, toxic analogs of tryptophan pathway
      intermediates. Plants homozygous for trp3-1 and trp3-2 are light-conditional
      tryptophan auxotrophs, while trp3-100 is a more leaky mutant. Genetic
      complementation crosses demonstrated that the three mutations are allelic to each
      other, and define a new complementation group. All three mutants have decreased
      steady-state levels of tryptophan synthase alpha protein, and the trp3-100
      polypeptide exhibits altered electrophoretic mobility. All three mutations were
      shown to be in the TSA1 (tryptophan synthase alpha subunit) structural gene by
      several criteria. Firstly, the trp3-1 mutation is linked to TSA1 on the bottom of
      chromosome 3. Secondly, the trp3-1 mutation was complemented when transformed
      with the wild-type TSA1 gene. Finally, DNA sequence analysis of the TSA1 gene
      revealed a single transition mutation in each trp3 mutant.

PMID- 9003323
TI  - A second site-specific recombination event in the lambdoid bacteriophage HK022.
AB  - An in vitro site-specific recombination reaction of the lambdoid phage HK022 has
      revealed two supercoiled products that proved to be Holliday intermediates. One
      of them is the Holliday intermediate which has resulted from an attP x attB
      reaction. The other is an intermediate which has resulted from a recombination
      reaction between attP and the attL site of the product from the first reaction.
      The preferential attL x attP over attR x attP reaction was confirmed in vitro and
      in vivo by challenging attP sites with attL and attR sites. The biased attP x
      attL over attP x attR reaction in phage HK022 is discussed.

PMID- 9003324
TI  - Phenotypic reversion of the gypsy-induced mutation scD1 of Drosophila
      melanogaster by replicative transposition of a sc enhancer to the yellow gene and
      by mutations in the enhancer of yellow and zeste loci.
AB  - Both mutations of Drosophila melanogaster in the y2scD1 strain are caused by the
      insertion of gypsy, but the scD1 mutation contains, in addition, an insertion of
      the jockey mobile element at a distance of 1.8 kb from gypsy. The su(Hw)-binding
      region in the copy of gypsy in scD1 inhibits scute expression in several specific
      areas of the epithelium, and in particular, blocks the formation of anterior
      notopleural (ANP) bristles. The y2 reversions y+2MC and y2#+9 restore the
      formation of ANP bristles. Molecular analysis revealed that both revertants were
      induced by transposition into the gypsy element at the yellow locus of jockey and
      an adjacent 1.8-kb region of the scute gene which contains an enhancer
      responsible for the development of ANP bristles. The duplicated enhancer is not
      insulated by the su(Hw)-binding region and can interact with the scute promoter
      in spite of the presence of two other promoters between them. Hypomorphic
      mutation in the e(y)2 gene and zOp6 allele partially inhibit ANP bristle
      formation in flies with y+2MC and y2+9 mutations. In addition, we found that
      mutations in the e(y)1, e(y)3 and zeste genes may interfere with transcriptional
      insulation by the su(Hw)-binding region in the scD1 allele.

PMID- 9003325
TI  - The fucoxanthin-chlorophyll proteins from a chromophyte alga are part of a large
      multigene family: structural and evolutionary relationships to other light
      harvesting antennae.
AB  - A fucoxanthin-chlorophyll protein (FCP) cDNA from the raphidophyte Heterosigma
      carterae encodes a 210-amino acid polypeptide that has similarity to other FCPs
      and to the chlorophyll a/b-binding proteins (CABs) of terrestrial plants and
      green algae. The putative transit sequence has characteristics that resemble a
      signal sequence. The Heterosigma fcp genes are part of a large multigene family
      which includes members encoding at least two significantly different polypeptides
      (Fcp1, Fcp2). Comparison of the FCP sequences to the recently determined three
      dimensional structure of the pea LHC II complex indicates that many of the key
      amino acids thought to participate in the binding of chlorophyll and the
      formation of complex-stabilizing ionic interactions are well conserved.
      Phylogenetic analyses of sequences of light-harvesting proteins shows that the
      FCPs of several chromophyte phyla form a natural group separate from the
      intrinisic peridinin-chlorophyll proteins (iPCPs) of the dinoflagellates:
      Although the FCP and CAB genes shared a common ancestor, these lineages diverged
      from each other prior to the separation of the CAB LHC I and LHC II sequences in
      the green algae and terrestrial plants.

PMID- 9003327
TI  - Measuring the toxic effects of high gene dosage on yeast cells.
AB  - A novel method, which is rapid, reliable and quantitative, is presented for
      measuring the toxic effects on yeast cells of high dosage of any given gene. It
      is based on the possibility of monitoring the presence in cells of a plasmid
      carrying the ADE2 gene from Saccharomyces cerevisiae by direct observation of
      colonies, the construction of this particular plasmid being easily made by marked
      homologous recombination in yeast. Four yeast regulatory genes tested were found
      to result in various degrees of toxicity at high dosage. Possible implications of
      the measurement of gene toxicity for eukaryotic cell regulatory mechanisms and
      for the use of novel general approaches to gene selection, such as the gene-gene
      interference method, are discussed.

PMID- 9003326
TI  - The Schizosaccharomyces pombe map1 gene encodes an SRF/MCM1-related protein
      required for P-cell specific gene expression.
AB  - Cells of Schizosaccharomyces pombe undergo mating and meiosis when starved for a
      nitrogen source. In this process a P and and M cell first mate to generate a
      diploid zygote, which subsequently enters meiosis and sporulates. The P mating
      type is controlled by the mat1-Pc gene at the mating type locus, together with a
      gene called map1. We show that these two functions are required for expression of
      the P-specific gene map3. We have cloned the map1 gene and show that it encodes a
      putative MADS-box containing transcription factor related to mammalian Serum
      Response Factor (SRF) and Saccharomyces cerevisiae MCM1. The Mat1-Pc protein
      contains a motif characteristic for proteins that interact with MADS-box factors,
      suggesting that Mat-Pc and Map1 may form a heterodimer that activates the P
      specific map3 gene.

PMID- 9003328
TI  - A RecA/RAD51 homologue from a hyperthermophilic archaeon retains the major RecA
      domain only.
AB  - A gene encoding a RecA/RAD51 homologue from a hyperthermophilic archaeon,
      Pyrococcus sp. KOD1 (Pk), was cloned, sequenced and expressed in Escherichia
      coli. The deduced 210-amino acid sequence was compared to homologues from
      bacteria (RecA), eukaryotes (RAD51, DMC1) and archaea (RadA). The entire protein
      from Pk (Pk-REC) basically corresponds to the essential central domain of its
      counterparts and lacks the two smaller RecA subdomains at the N- and C-termini.
      The sequence comparison suggests that Pk-REC represents a common prototype of
      RecA, RAD51, DMC1 and RadA, with higher enzymatic activity. Recombinant Pk-REC
      was fully active and complemented the ultraviolet light sensitivity of an E. coli
      recA mutant strain.

PMID- 9003329
TI  - Interpreting the prism adaptation study.

PMID- 9003330
TI  - Excimer laser keratectomy for astigmatism after PK.

PMID- 9003331
TI  - Preferred practice patterns.

PMID- 9003332
TI  - Treatment of intraocular retinoblastoma with carboplatin and etoposide
      chemotherapy.
AB  - PURPOSE: Management of intraocular retinoblastoma was initiated with 2-drug
      chemotherapy in an effort to improve the rate of vision preservation and ocular
      salvage and to avoid or delay the use of external beam radiation treatment.
      METHODS: Six patients with intraocular retinoblastoma (five bilateral; one
      unilateral, 1 month old) received 6 to 7 monthly cycles of intravenously
      administered carboplatin and etoposide (VP-16) as primary treatment. No eyes were
      enucleated primarily. Twelve of the 33 discrete tumors in the 11 study eyes
      received prophylactic supplemental treatment with cryotherapy or laser
      hyperthermia. Response was documented with frequent eye examinations with the
      patient under general anesthesia and with repeated fundus photography. RESULTS:
      All eight larger tumors (> 10-mm diameter) underwent dramatic regression after
      treatment with chemotherapy alone, and six of these tumors ultimately became
      fully calcific. One larger tumor and two smaller tumors showed post-treatment
      growth, each within 2 months after completion of chemotherapy. Six larger tumors
      were observed without growth or further treatment for 7 to 21 months after
      completion of chemotherapy. Subretinal fluid resorbed completely in four of four
      eyes with extensive retinal detachment, and vitreous seeding diminished
      considerably in four of four eyes. In five eyes, intraocular disease recurrence
      at a distance from any initially observed tumor eventually required treatment
      with external beam radiation (three eyes) or enucleation (three eyes). Eight of
      11 involved eyes were salvaged, including 5 of 8 with larger tumors and 4 of 4
      with vitreous seeding; 4 retained eyes received no radiation exposure, including
      3 with larger tumors and 1 with vitreous seeding. Good vision was preserved in
      six eyes, two of which were markedly improved after occlusion therapy for
      amblyopia. There was no extraocular disease recurrence and no serious harm from
      treatment during observation ranging from 12 to 40 months after diagnosis.
      CONCLUSION: Chemotherapy with carboplatin and etoposide shows promise as initial
      treatment for intraocular retinoblastoma. Further study is indicated to define
      its proper role in the management of this disease.

PMID- 9003333
TI  - Congenital neoplasms of the nonpigmented ciliary epithelium (medulloepithelioma).
AB  - BACKGROUND: Most reports on intraocular medulloepithelioma have been single case
      descriptions. The authors reviewed ten patients with intraocular
      medulloepithelioma, discuss some little known clinical features of this entity,
      and make diagnostic and therapeutic recommendations. PATIENTS AND METHODS: The
      records of the authors' patients with histopathologically confirmed
      medulloepithelioma were reviewed, and the clinical features, diagnostic problems,
      management, histopathology, and prognosis were assessed. RESULTS: Of the ten
      patients, nine were children, ranging in age from 2 months to 10 years, and one
      patient was 58 years of age at the time of clinical presentation. In seven
      patients, there was a delay in diagnosis, ranging from 3 to 28 months, and four
      patients underwent surgery for cataract, glaucoma, or other secondary conditions
      while the tumor was unsuspected. All patients had a nonpigmented ciliary body
      mass and a notched or subluxated lens, and six had neovascular glaucoma and
      evident cysts in the mass. The authors' initial management was enucleation in
      four patients and local resection in six. Of the six patients managed by local
      resection, five eventually required enucleation, four because of local tumor
      recurrence and one because of ocular inflammation and discomfort. Pathologically,
      nine tumors were classified as malignant (5 teratoid, 4 nonteratoid) and one as
      benign. In one patient (the adult), metastasis to the parotid gland developed.
      CONCLUSION: Intraocular medulloepithelioma generally occurs in the first decade
      of life as a nonpigmented ciliary body mass. It has a tendency to cause secondary
      neovascular glaucoma, a characteristic lens notch and subluxation, and a
      neoplastic cyclitic membrane. Enucleation is the best treatment for advanced
      cases. For smaller circumscribed lesions, local resection may be attempted, but
      such treatment is followed frequently by local recurrence. Although most
      medulloepitheliomas are cytologically malignant, distant metastasis is uncommon.

PMID- 9003334
TI  - Acquired neoplasms of the nonpigmented ciliary epithelium (adenoma and
      adenocarcinoma).
AB  - BACKGROUND/PURPOSE: Acquired neoplasms of the nonpigmented ciliary body
      epithelium (NPCE) are rare, and most information about them has come from single
      case reports. This study was undertaken to review the authors' experience with a
      series of patients with acquired neoplasms of the NPCE, to delineate the clinical
      and histopathologic features of these tumors, and show how they differ from
      ciliary body melanoma. METHODS: A clinicopathologic review was conducted on
      acquired tumors of the NPCE that were evaluated by the authors and a review of
      the English language literature was done. The data from the authors' cases were
      compared with previously reported cases. RESULTS: The authors had personal
      experience with nine patients with acquired tumors of the NPCE and found 18 other
      patients with these tumors in the literature. Of the authors' patients, all
      tumors were predominantly nonpigmented and were white to light-tan in color.
      Associated clinical findings included signs of intraocular inflammation in all
      patients, secondary cataract in eight (89%), and subluxation of the lens in six
      (67%). Eight of the tumors were managed successfully by local resection and one
      by enucleation. Histopathologically, the tumors showed considerable variation
      from patient to patient. Seven tumors were classified as benign adenoma and two
      as low-grade adenocarcinoma. There was no local recurrence or systemic
      metastases. Although tumors of the NPCE historically have been misdiagnosed
      clinically as ciliary body melanoma, our study suggests that they have some
      characteristic features that severe to differentiate them from melanoma and other
      ciliary body lesions. In contrast to melanoma, acquired neoplasms of the NPCE are
      amelanotic and are more likely to have an irregular surface, associated
      inflammatory signs, to transmit light well during transillumination, and show
      high internal reflectivity with ultrasonography. CONCLUSION: Acquired neoplasms
      of the NPCE have characteristic clinical and histopathologic features that should
      suggest the diagnosis. Due to their anterior location in the ciliary body, local
      resection (rather than enucleation) is usually the treatment of choice. The
      visual prognosis is fair, and the systemic prognosis is excellent.

PMID- 9003335
TI  - Block excision of tumors of the anterior uvea. Report on 68 consecutive patients.
AB  - PURPOSE: This study describes the authors' surgical technique and the results in
      68 consecutive patients with tumors of the iris and ciliary body involving the
      angle removed by block excision and tectonic corneoscleral grafting between 1980
      and 1995. PATIENTS AND METHODS: There were 41 (60.3%) women and 27 (39.7%) men
      whose ages ranged from 14 to 85 years (median, 41 years). Follow-up ranged from
      0.5 to 15.2 years (median, 6.3 years). Tumors of the iris and ciliary body with
      chamber angle involvement were removed with a modified block excision consisting
      of simultaneous en bloc removal of the tumor with adjacent iris and cornea and
      sclera in full-thickness. The resulting defect of 6 to 20 mm (median, 9.0 mm)
      diameter is covered with a tectonic corneoscleral graft. RESULTS: Forty-nine
      tumors (72.1%) were classified as malignant tumors of the iris and ciliary body.
      Twenty-one (44.7%) of 47 malignant melanomas showed histologic evidence of
      scleral invasion of more than one third of scleral thickness. Extrascleral
      extension of the tumor was present in seven (14.9%) patients with malignant
      melanomas and in four (21.1%) patients with benign tumors of the iris and ciliary
      body. The 10-year survival probability of patients with malignant melanomas was
      91.4%. The main intraoperative complication was vitreous hemorrhage in 24 (35.3%)
      patients, and the main postoperative complication was complicated cataract,
      occurring in 22 (32.3%) patients. Two local tumor recurrences (2.9%) were
      observed. Four eyes (5.8%) had to be enucleated after block excision. Best
      corrected postoperative visual acuity was better than 20/60 in 36 (52.9%)
      patients. CONCLUSIONS: The authors' results indicate that block excision with
      tectonic corneoscleral grafting may be the treatment of choice for progressive
      circumscribed tumors of the iris and ciliary body involving the anterior chamber
      angle up to 150 degrees of its circumference.

PMID- 9003336
TI  - Photodynamic therapy of pigmented choroidal melanomas of greater than 3-mm
      thickness.
AB  - PURPOSE: The purpose of the study is to determine the effect of photodynamic
      therapy in the destruction of experimental pigmented choroidal melanomas > or = 3
      mm in thickness using a liposomal preparation of benzoporphyrin derivative,
      verteporfin. METHODS: Pigmented choroidal tumors were established in 32 New
      Zealand albino rabbit eyes. Animals were treated with daily injections of
      cyclosporine, and tumor growth was followed by serial fundus examinations and
      ultrasonography. When a tumor exceeded 3 mm in thickness (tumor height ranged
      from 3.1-4.6 mm), the authors administered benzoporphyrin derivative
      intravenously (1 mg/kg) and irradiated the tumor at 692-nm through an argon
      pumped dye laser at different total light doses ranging from 60 to 120 J/cm2.
      Control animals were treated with light or benzoporphyrin derivative only. Each
      animal then was followed-up for 4 to 6 weeks by fundus photography, fluorescein
      angiography, and ultrasonography. RESULTS: All animals treated with
      benzoporphyrin derivative and light at fluences of > or = 80 J/cm2 showed
      complete tumor arrest. In contrast, both control groups showed continuous tumor
      growth in all animals with tumors filling most of the vitreous cavity by 3 weeks.
      Histologic examination results of tumors treated with dye plus light immediately
      after treatment showed prominent vascular closure. No vascular changes were noted
      in the control eye treated with light or dye alone. Examination results of the
      eyes that showed tumor regression after a 4-week follow-up period showed tumor
      necrosis and extensive infiltration of mononuclear cells and pigment-laden
      macrophages at the tumor site. CONCLUSIONS: These data suggest that photodynamic
      therapy may have a role in the management of pigmented choroidal melanomas.

PMID- 9003337
TI  - Factors influencing visual acuity after photocoagulation for subfoveal choroidal
      neovascularization of exudative age-related macular degeneration.
AB  - PURPOSE: To evaluate factors influencing visual acuity after laser
      photocoagulation for subfoveal choroidal neovascularization of exudative age
      related macular degeneration. METHODS: Subfoveal choroidal neovascular membranes
      were photocoagulated. Factors favoring a visual acuity of 20/200 or better were
      analyzed using Fisher's exact probability test or chi-square test on 28 eyes in
      which visual acuity was 20/200 or better, and 23 eyes with a visual acuity below
      20/200 at the most recent follow-up examination. RESULTS: Factors predicting a
      postoperative visual acuity of 20/200 or better were (1) distance between one
      lateral margin of the neovascular membrane and the center of the foveal avascular
      zone was one-third disc diameter or less, and (2) pretreatment retinal
      sensitivity at the fixation point was 10 dB or more. CONCLUSION: Good indications
      for photocoagulation treatment of subfoveal choroidal neovascular membrane were a
      neovascular membrane margin near the center of the foveal avascular zone and
      relatively good retinal sensitivity at the fixation point adjacent to the
      scotoma. These factors predict a visual acuity of 20/200 or better after
      treatment.

PMID- 9003338
TI  - Deep retinal vascular anomalous complexes in advanced age-related macular
      degeneration.
AB  - PURPOSE: The authors describe the clinical characteristics of a group of patients
      with age-related macular degeneration (AMD), deep retinal vascular anomalous
      complexes (RVACs), advanced Bruch membrane changes, and severe visual loss. Based
      on clinical evaluation and imaging studies, the authors hypothesize the cause of
      such retinal vascular formations. PATIENTS AND METHODS: The authors quantified an
      initial case series of 6 patients and expanded it to 11 patients (14 eyes) with
      AMD and RVACs diagnosed by fluorescein angiography or slit-lamp examination.
      Associated pigment epithelial detachments (PEDs) of 13 eyes are described. In
      addition to the clinical and fluorescein angiography descriptions, infrared
      imaging and indocyanine green angiography were used to characterize more recently
      described RVACs and fellow eyes. RESULTS: Each study eye had a clearly defined
      anastomosis connecting the retinal circulation to a vascular complex in the deep
      retina. The RVACs associated with PEDs assumed a more central location than did
      typical choroidal neovascularization associated with PEDs. In seven eyes with
      RVACs, there were clinically recognizable retinovascular findings: intraretinal
      hemorrhages, telangiectasia, or microaneurysms. Legal blindness occurred in 9 of
      11 patients. CONCLUSION: These results indicate that retinovascular changes can
      be associated with nondisciform AMD. The authors speculate that neurodegenerative
      changes and hypoxia may lead to such changes, the RVAC being a more advanced
      finding. Closure of an RVAC with photocoagulation is difficult, perhaps because
      of its higher blood flow. The visual outcome is poor, not only because of the
      advanced state of the underlying AMD, but also because of the exudative nature of
      the RVAC.

PMID- 9003339
TI  - Classification of choroidal neovascularization by digital indocyanine green
      videoangiography.
AB  - PURPOSE: The majority of patients with exudative maculopathy due to age-related
      macular degeneration present with poorly defined or occult choroidal
      neovascularization (CNV) that cannot be imaged adequately by fluorescein
      angiography. Digital indocyanine green (ICG) videoangiography is a new technique
      that allows enhanced imaging of these poorly defined or occult vessels. The
      authors studied 1000 consecutive cases of occult CNV using digital ICG
      angiography to describe the various types of neovascularization observed by this
      technique and to determine the frequency and natural history of the various
      lesions. MATERIALS AND METHODS: Digital ICG videoangiography was performed as
      described previously on 1000 consecutive eyes with occult CNV by fluorescein
      angiography. RESULTS: One thousand consecutive eyes with occult CNV by
      fluorescein angiography were imaged using digital ICG videoangiography. Three
      morphologic types of CNV were noted by ICG videoangiography, which included focal
      spots, plaques (well-defined or poorly defined), and combination lesions (in
      which both focal spots and plaques are noted). Combination lesions can be
      subdivided into marginal spots (focal spots at the edge of plaques of
      neovascularization), overlying spots (hot spots overlying plaques of
      neovascularization), or remote spots (a focal spot remote from a plaque of
      neovascularization). The relative frequency of these lesions was as follows:
      there were 283 cases (29%) of focal spots; 597 cases (61%) of plaques, consisting
      of 265 cases (27%) of well-defined plaques and 332 cases (34%) of poorly defined
      plaques; and 84 cases (8%) of combination lesions, consisting of 35 cases (3%) of
      marginal spots, 37 cases (4%) of overlying spots, and 12 cases (1%) of remote
      spots. In seven additional cases (1%), a mixture of the above lesions was noted.
      In 13 additional eyes (1%), no lesions were noted on the ICG angiogram. The
      studies of 16 eyes were unreadable or unobtainable. CONCLUSIONS: There are three
      types of CNV that can be observed by digital ICG videoangiography. Plaques are
      the most common type and have a poor natural history. Focal spots or hot spots
      are the next most frequently seen lesion and can potentially be treated by ICG
      guided laser photocoagulation. Combination lesions, in which both focal spots and
      plaques are present, are rare. This study of 1000 consecutive cases of eyes with
      occult neovascularization that were imaged with digital ICG videoangiography
      serves to classify the various types of neovascularization observed by this
      technique. Digital ICG videoangiography is an important tool in better
      delineating eyes with occult CNV. Future studies are necessary to validate our
      findings.

PMID- 9003340
TI  - Subfoveal choroidal neovascularization in punctate inner choroidopathy. Surgical
      management and pathologic findings.
AB  - PURPOSES: To evaluate submacular surgery for the management of subfoveal
      choroidal neovascularization in punctate inner choroidopathy, to describe the
      histopathology and ultrastructure of the excised subretinal tissue, and to
      propose a staging system that characterizes the development of choroidal
      neovascularization with associated subretinal fibrosis. METHODS: The authors
      reviewed the records of five patients (6 eyes) with punctate inner choroidopathy
      who underwent submacular surgery for subfoveal choroidal neovascularization.
      Surgical specimens were examined using light and transmission electron
      microscopy. RESULTS: Visual improvement was noted postoperatively in all six
      eyes, with follow-up ranging from 8 to 36 months (median, 14 months). Recurrences
      (6 in 4 eyes) were common. Five of the six recurrences required additional
      procedures: three were managed surgically, two with laser photocoagulation, and
      one with observation. "Bridging" of separate foci of choroidal neovascularization
      resulted in stellate or "dumbbell-shaped" areas of subretinal fibrosis in four of
      six eyes. Histopathologic evaluation of the excised tissue showed endothelial
      lined vascular channels, retinal pigment epithelium, lymphocytes, plasma cells,
      fibrocytes, collagen fragments, and rarely, outer retinal elements. CONCLUSIONS:
      Subfoveal choroidal neovascularization in punctate inner choroidopathy may be
      managed with submacular surgery. Recurrences are common and may result in
      substantial loss of vision. Choroidal neovascular membranes with an accompanying
      fibrotic reaction are responsible for the stellate or dumbbell-shaped areas of
      subretinal fibrosis. No beneficial effect was demonstrated using corticosteroid
      treatment of the choroidal neovascularization.

PMID- 9003342
TI  - Central serous chorioretinopathy in patients with systemic lupus erythematosus.
AB  - PURPOSE: To describe three patients with systemic lupus erythematosus in whom
      ophthalmoscopic and fluorescein angiographic evidence of central serous
      chorioretinopathy developed. METHODS: The authors retrospectively reviewed the
      clinical and photographic records of three patients with systemic lupus
      erythematous in whom central serous chorioretinopathy developed. RESULTS:
      Ophthalmoscopic changes observed in these patients with systemic lupus
      erythematosus included discrete areas of clumping and mottling of the retinal
      pigment epithelium (RPE), focal RPE detachments, serous elevations of the
      neurosensory retina, and late subretinal fibrosis with scar formation.
      Fluorescein angiographic findings included transmission hypofluorescence and
      hyperfluorescence corresponding to focal RPE alterations, early punctate intense
      hyperfluorescence corresponding to RPE leaks with progressive filling of sub-RPE
      detachment spaces, and slow late filing of subretinal detachment spaces.
      CONCLUSION: Patients with systemic lupus erythematosus are at increased risk to
      have central serous chorioretinopathy develop. The pathogenetic implications for
      an association between systemic lupus erythematosus and central serous
      chorioretinopathy as well as the similarity to the chorioretinopathy seen with
      accelerated hypertension, pregnancy, hemodialysis, organ transplantation, and
      exogenous and endogenous hypercortisolism are discussed. Focal choroidal
      vasculature compromise with secondary dysfunction of overlying RPE cells is the
      proposed common mechanism.

PMID- 9003341
TI  - Central serous chorioretinopathy in younger and older adults.
AB  - PURPOSE: The purpose of the study is to investigate the demographic
      characteristics and clinical findings of central serous chorioretinopathy (CSC).
      METHODS: This study examined a consecutive series of 130 patients with CSC seen
      over an 18-month period. RESULTS: The mean age of the patients when examined was
      51 years, and the male-to-female ratio was 2.6:1.0. A total of 62 patients were
      older than 50 years of age when first examined. Although the patients shared some
      clinical and angiographic similarities, the older patients had a lower mean
      visual acuity and were more likely to have diffuse retinal pigment
      epitheliopathy, bilateral involvement, and secondary choroidal neovascularization
      than were the younger patients. With ophthalmoscopic and angiographic examination
      results, it was possible to differentiate CSC in older adults from choroidal
      neovascularization. CONCLUSION: This study expands the clinical concept of CSC.
      The male-to-female ratio was much lower, and the range of ages of the patients
      was much greater than in previous studies. Disease manifestations in older adults
      differed somewhat from those seen in younger adults. In older patients, CSC can
      be distinguished from other exudative maculopathies, particularly that of
      choroidal neovascularization secondary to age-related macular degeneration.

PMID- 9003343
TI  - Reversal of visual loss with hyperbaric oxygen treatment in a patient with Susac
      syndrome.
AB  - PURPOSE: The purpose of the study is to report on a 34-year-old woman with Susac
      syndrome who presented on two separate occasions with visual acuity loss from a
      recurrent branch retinal artery occlusion and underwent hyperbaric oxygen
      treatment with favorable outcome. METHODS: Visual acuity was 20/400 in the left
      eye and count fingers in the right eye after separate occlusive events. The
      patient underwent hyperbaric oxygen treatment on each occasion of visual acuity
      loss. The patient subsequently was diagnosed with Susac syndrome (microangiopathy
      of the retina, brain, and middle ear). The authors present visual fields,
      photographs, angiograms, and ancillary tests documenting diagnosis and course of
      treatment. RESULTS: On each occasion, visual acuity improved to 20/25 during and
      was maintained after hyperbaric oxygen treatment. Visual fields showed
      improvement immediately after treatment. CONCLUSION: This is the first report of
      hyperbaric oxygen treatment for Susac syndrome. Dramatic post-treatment visual
      field and acuity changes suggest benefit of treatment. Hyperbaric oxygen
      treatment can be considered a treatment option for visual complications of this
      syndrome. Susac syndrome should be included in the differential diagnosis of
      recurrent branch retinal artery occlusion.

PMID- 9003344
TI  - Inhibition of preretinal and optic nerve head neovascularization in pigs by
      intravitreal triamcinolone acetonide.
AB  - PURPOSE: The authors tested the antiangiogenic properties of intravitreally
      administered triamcionolone acetonide in a pig model of preretinal
      neovascularization to determine the effectiveness of this therapy in preventing
      neovascularization. METHODS: In 14 eyes of seven pigs, branch retinal vein
      occlusions were created in a standardized manner using photodynamic thrombosis
      with rose bengal dye and thermal burns from the argon green laser. Intravitreal
      injection of approximately 4 mg of triamcinolone acetonide was performed in one
      eye of each animal, and eyes were followed clinically for 12 weeks with
      ophthalmoscopy and fundus photography. A standardized grading system was
      developed to permit masked assessment of disc proliferations from fundus
      stereophotographs. After death, all neovascularization was confirmed
      histopathologically and a final grade was assigned to each eye. Statistical
      analysis employed use of a nonparametric test of the paired data. RESULTS:
      Significant inhibition of neovascularization was observed in triamcinolone
      treated eyes (P = 0.0156). Although none of the steroid-injected eyes
      demonstrated clinically evident new vessels, histopathologic and photographic
      analysis results demonstrated fine new vessels on the optic disc in four eyes. In
      all of the untreated eyes, neovascularization of a moderate (II) to high (III to
      IV) grade developed. CONCLUSIONS: Intravitreal triamcinolone acetonide
      effectively inhibited preretinal and optic nerve head neovascularization in the
      pig model. The grading system used permitted masked assessment of outcome and
      paired analysis allowed a conclusion to be drawn from a relatively small number
      of eyes. The mechanisms by which triamcinolone acetonide inhibits
      neovascularization remain to be elucidated.

PMID- 9003345
TI  - Comparative optic disc analysis in normal pressure glaucoma, primary open-angle
      glaucoma, and ocular hypertension.
AB  - PURPOSE: The authors wished to determine whether characteristics of optic disc
      and parapapillary atrophy differ between eyes with ocular hypertension, primary
      open-angle glaucoma (POAG) and those with normal-pressure glaucoma, including a
      subset of patients with normal-pressure glaucoma with evidence of serum
      abnormalities of humoral autoimmunity. METHODS: Three hundred ninety-two eyes of
      196 patients with ocular hypertension, 394 eyes of 197 patients with POAG, and
      135 eyes of 68 patients with normal-pressure glaucoma were analyzed. Nerve fiber
      layer hemorrhage in the optic disc region, retinal arteriolar narrowing, and
      morphometric parameters of optic disc and parapapillary atrophy were investigated
      in these groups. Parapapillary atrophy was differentiated in two different zones
      (alpha and beta). RESULTS: Nerve fiber layer hemorrhage and arteriolar narrowing
      were found more frequently in patients with normal-pressure glaucoma than in
      patients with POAG (P = 0.014, P = 0.004) and ocular hypertension (P < 0.0001, P
      < 0.0001). Zone beta was detected more often in patients with normal-pressure
      glaucoma than in those with ocular hypertension (P < 0.001) and POAG (P = 0.013).
      Although patients with normal-pressure glaucoma had more advanced neural rim loss
      and larger parapapillary atrophy, there were similar correlations between neural
      rim area and the area and extension of parapapillary atrophy in patients with
      normal-pressure glaucoma and POAG. Parapapillary atrophy parameters also were
      similar in different stages of neural rim damage in patients with normal-pressure
      glaucoma and POAG (P > 0.05). Optic disc characteristics were not different (P >
      0.05) between the subgroups of patients with normal-pressure glaucoma.
      CONCLUSION: The authors' findings support the idea that besides the enlargement
      of the area and extension of parapapillary atrophy that accompanies neural damage
      in glaucoma, the severity of the parapapillary atrophy also increases as assessed
      by the increase in zone beta in more damaged eyes. Furthermore, the final
      clinical appearance of optic nerve damage is similar among patients with POAG,
      normal-pressure glaucoma, and the subgroups of normal-pressure glaucoma,
      regardless of their possibly different mechanisms of neuropathy.

PMID- 9003346
TI  - Retinal nerve fiber layer thickness in normal human eyes.
AB  - PURPOSE: To measure the histologic thickness of the retinal nerve fiber layer
      (RNFL) in normal human eyes. METHODS: Human eyes were obtained at autopsy within
      6 hours postmortem. The retina was dissected into four quadrants and serially
      sectioned in historesin. The RNFL thickness was measured histologically in all
      four quadrants at the disc margin and at regular intervals from the disc margin.
      Measurements of the RNFL thickness also were obtained at the fovea and in the
      retinal periphery. RESULTS: Ten eyes of ten white individuals were studied. Age
      (mean +/- standard deviation) was 53.1 +/- 19.6 years (range, 18-76 years). For
      the eyes studied, the disc area (mean +/- standard deviation) and cup:disc ratio
      (mean +/- standard deviation) were 1.92 +/- 0.1 mm2 and 0.3 +/- 0.08,
      respectively. Mean superior, inferior, nasal, and temporal RNFL thickness at the
      disc margin was 405, 376, 372, and 316 microns, respectively. In all four
      quadrants, the RNFL thickness decreased with increasing distance from the disc
      margin. The average superior and inferior RNFL thickness was inversely related to
      age (P = 0.033, P = 0.097, respectively). The average RNFL thickness was not
      related to disc area. The average RNFL thickness just superior, inferior, nasal,
      and temporal to the foveola was 27, 34, 26, and 12 microns, respectively. The
      average RNFL thickness just posterior to the ora serrata in the superior,
      inferior, nasal, and temporal retinal periphery was 8 to 11 microns. CONCLUSION:
      The peripapillary RNFL thickness in humans is thicker than that seen in nonhuman
      primates. The thinnest peripapillary RNFL is in the region of the papillomacular
      bundle. These data can be used to determine the accuracy of NFL analyzers in
      obtaining in vivo RNFL thickness measurements.

PMID- 9003347
TI  - Optic disc in fundus coloboma.
AB  - PURPOSE: To categorize and describe the type of optic disc involvement and blood
      vessel patterns seen in patients with fundus coloboma. METHODS: This is a
      prospective study involving 67 eyes of 40 patients with choroidal coloboma. The
      evaluation included documentation of fundus details using fundus drawings or
      photographs, or both. RESULTS: Six types of disc involvement were identified: (1)
      normal disc outside fundus coloboma (27.8%); (2) disc outside the fundus coloboma
      and abnormal (10.4%); (3) disc outside the fundus coloboma and independently
      colobomatous (8.9%); (4) disc within the fundus coloboma and normal (5.0%); (5)
      disc within the fundus coloboma and colobomatous (44.3%); and (6) disc shape not
      identified but blood vessels seen emanating from the superior border of the large
      fundus coloboma (2.9%). Visual acuity was better in types I, II, and III compared
      with IV, V, and VI. Microphthalmos was more common with the more severe
      anomalies. High myopia was more common in the less severe anomalies. CONCLUSION:
      Optic disc involvement in fundus coloboma is widely variable. Of fundus
      colobomas, 67.2% are associated with either a frankly colobomatous or an altered
      disc. Of the discs located outside fundus colobomas, 41% are also abnormal.
      Visual acuity was better in types I, II, and III.

PMID- 9003348
TI  - Peripheral retinopathy in offspring of carriers of Norrie disease gene mutations.
      Possible transplacental effect of abnormal Norrin.
AB  - BACKGROUND: The Norrie disease (ND) gene (Xp11.3) (McKusick 310600) consists of
      one untranslated exon and two exons partially translated as the Norrie disease
      protein (Norrin). Norrin has sequence homology and computer-predicted tertiary
      structure of a growth factor containing a cystine knot motif, which affects
      endothelial cell migration and proliferation. Norrie disease (congenital retinal
      detachment), X-linked primary retinal dysplasia (congenital retinal fold), and X
      linked exudative vitreoretinopathy (congenital macular ectopia) are allelic
      disorders. METHODS: Blood was drawn for genetic studies from members of two
      families to test for ND gene mutations. Sixteen unaffected family members were
      examined ophthalmologically. If any retinal abnormality were identified, fundus
      photography and fluorescein angiography was performed. RESULTS: Family A had ND
      (R109stp), and family B had X-linked exudative vitreoretinopathy (R121L). The
      retinas of 11 offspring of carrier females were examined: three of seven carrier
      females, three of three otherwise healthy females, and one of one otherwise
      healthy male had peripheral inner retinal vascular abnormalities. The retinas of
      five offspring of affected males were examined: none of three carrier females and
      none of two otherwise healthy males had this peripheral retinal finding.
      CONCLUSIONS: Peripheral inner retinal vascular abnormalities similar to regressed
      retinopathy of prematurity were identified in seven offspring of carriers of ND
      gene mutations in two families. These ophthalmologic findings, especially in four
      genetically healthy offspring, strongly support the hypothesis that abnormal
      Norrin may have an adverse transplacental (environmental) effect on normal inner
      retinal vasculogenesis.

PMID- 9003349
TI  - Idiopathic granulomatous orbital inflammation.
AB  - PURPOSE: Granulomatous orbital inflammation may occur as an isolated condition of
      unknown origin. These idiopathic granulomatous lesions are believed to belong to
      the orbital pseudotumor group by some authors, whereas others consider them
      sarcoidosis limited to the orbit. The aim of this study is to define the
      clinicotherapeutic aspects of these lesions. METHODS: The records of all patients
      with diagnosis of orbital pseudotumor and orbital sarcoidosis from the Orbital
      Center Amsterdam in the period between 1976 and 1994 were reviewed to define
      those with idiopathic granulomatous orbital inflammation. The authors studied the
      clinicotherapeutic aspects and histopathology of idiopathic granulomatous orbital
      inflammation by analysis of their own series and the literature. RESULTS: Their
      study group encompassed seven patients with idiopathic granulomatous orbital
      inflammation. The mean follow-up was 9.5 years (range, 3.5-16.0 years). All had
      unilateral orbital presentation, with localization in the lacrimal gland in three
      patients. The lesions clinically presented with signs of mass effect or
      inflammation or both and were treated successfully with surgery, systemic
      corticosteroids, a combination of surgery and systemic corticosteroids, or
      systemic corticosteroids followed by irradiation. Histopathologic analysis showed
      a spectrum of granulomatous inflammation, admixed with nongranulomatous
      inflammation and fibrosis. There have been 30 similar cases described in the
      literature with comparable clinicotherapeutic characteristics. CONCLUSIONS: Based
      on this study and the literature, it appears that idiopathic granulomatous
      orbital inflammation is more related to orbital pseudotumor than to orbital
      sarcoidosis.

PMID- 9003350
TI  - Characterization of epiretinal membranes using optical coherence tomography.
AB  - OBJECTIVE: To evaluate optical coherence tomography (OCT), a novel noncontact and
      noninvasive imaging technique, for the diagnosis and quantitative
      characterization of epiretinal membranes. METHODS: Optical coherence tomography
      is similar to an ultrasound B-scan, except that light rather than sound is used,
      which enables higher resolution. Over a 2-year period, OCT was used to examine
      186 eyes of 160 patients who had a diagnosis of an epiretinal membrane. Optical
      coherence tomograms were correlated with visual acuity, slit-lamp biomicroscopy,
      fluorescein angiography, and funds photography. RESULTS: Based on OCT, the
      epiretinal membrane was clearly separated from the retina with focal points of
      attachment in 49 eyes and globally adherent (no observed separation) in 125 eyes.
      Globally adherent membranes were associated with the following features: macular
      pseudohole (32 eyes), a difference in optical reflectivity between the membrane
      and retina (65 eyes), and/or a visible membrane tuft or edge (92 eyes). The
      membrane was undetectable on OCT in 12 eyes. The membrane thickness (mean +/-
      standard deviation) was 61 +/- 28 microns in the 169 eyes in which the thickness
      could be measured with OCT. Mean central macular thickness measured with OCT
      correlated with visual acuity (R2 = 0.73). CONCLUSION: Optical coherence
      tomography was able to provide a structural assessment of the macula that was
      useful in the preoperative and postoperative evaluation of epiretinal membrane
      surgery. Quantitative measurements and the assessment of membrane adherence with
      OCT may be useful in characterizing the surgical prognosis of eyes with an
      epiretinal membrane.

PMID- 9003351
TI  - Visual field defects after macular hole surgery. A new finding.
AB  - PURPOSE: The purpose of the study is to report the problem of a temporal visual
      field defect occurring after macular hole surgery. METHODS: The authors reviewed
      the records of 13 patients found to have visual field defects after vitrectomy
      for macular holes. Fluorescein angiograms (13 patients), optic nerve photographs
      (13 patients), focal electroretinograms (3 patients), and nerve fiber analyses (8
      patients) were performed in patients with visual field defects. RESULTS: An
      absolute, temporal, usually inferior field defect was noted in 13 patients. In
      eight patients, the defect was detected because of specific reports or
      retrospective field examination results. Five patients examined in a prospective
      manner were found to have field defects. No history of abnormal intraocular
      pressure or direct trauma to the optic nerve or retinal vessels was identified.
      Four patients showed optic nerve pallor and three had an anomalous-appearing
      disc. Focal electroretinograms were of similar amplitude in the involved retina
      compared to corresponding areas in the healthy fellow eye. Nerve fiber analysis
      showed a reduction in nerve fiber layer thickness correlating to the visual field
      defect in those eight patients in which this test was used. CONCLUSION: A
      significant temporal field defect may occur in patients after otherwise
      uncomplicated surgery for macular holes. The cause is unclear; however,
      reductions in nerve fiber layer thickness from the superior and nasal
      peripapillary area suggest that acute surgical release of the posterior hyaloid
      and the use of long-acting intraocular gas may in certain patients result in
      visual field defects.

PMID- 9003353
TI  - The Cu,Zn superoxide dismutase from Escherichia coli retains monomeric structure
      at high protein concentration. Evidence for altered subunit interaction in all
      the bacteriocupreins.
AB  - Gel-filtration chromatography experiments performed at high protein
      concentrations demonstrate that the Cu,Zn superoxide dismutase from Escherichia
      coli is monomeric irrespective of the buffer and of ionic strength. The catalytic
      activity of the recombinant enzyme is comparable with that of eukaryotic
      isoenzymes, indicating that the dimeric structure commonly found in Cu,Zn
      superoxide dismutases is not necessary to ensure efficient catalysis. The
      analysis of the amino acid sequences suggests that an altered interaction between
      subunits occurs in all bacterial Cu,Zn superoxide dismutases. The substitution of
      hydrophobic residues with charged ones at positions located at the dimer
      interface of all known Cu,Zn superoxide dismutases could be specifically
      responsible for the monomeric structure of the E. coli enzyme.

PMID- 9003354
TI  - Histamine reduces ZO-1 tight-junction protein expression in cultured retinal
      microvascular endothelial cells.
AB  - We examined ZO-1 protein content in cultured retinal vascular endothelial cells
      to test the hypothesis that histamine alters tight-junction-protein expression.
      Histamine (10(-9) -10(-4) M) causes a reversible concentration-dependent
      reduction of ZO-1 protein content, mediated by both H1 and H2 receptors.
      Histamine reduces ZO-1 expression within the time associated with increased
      paracellular permeability. Tight-junction-protein alterations may be a novel
      explanation for the mechanism by which vasoactive agents increase microvascular
      permeability.

PMID- 9003352
TI  - Quinoprotein-catalysed reactions.
AB  - This review is concerned with the structure and function of the quinoprotein
      enzymes, sometimes called quinoenzymes. These have prosthetic groups containing
      quinones, the name thus being analogous to the flavoproteins containing flavin
      prosthetic groups. Pyrrolo-quinoline quinone (PQQ) is non-covalently attached,
      whereas tryptophan tryptophylquinone (TTQ), topaquinone (TPQ) and lysine
      tyrosylquinone (LTQ) are derived from amino acid residues in the backbone of the
      enzymes. The mechanisms of the quinoproteins are reviewed and related to their
      recently determined three-dimensional structures. As expected, the quinone
      structures in the prosthetic groups play important roles in the mechanisms. A
      second common feature is the presence of a catalytic base (aspartate) at the
      active site which initiates the reactions by abstracting a proton from the
      substrate, and it is likely to be involved in multiple reactions in the
      mechanism. A third common feature of these enzymes is that the first part of the
      reaction produces a reduced prosthetic group; this part of the mechanism is
      fairly well understood. This is followed by an oxidative phase involving electron
      transfer reactions which remain poorly understood. In both types of dehydrogenase
      (containing PQQ and TTQ), electrons must pass from the reduced prosthetic group
      to redox centres in a second recipient protein (or protein domain), whereas in
      amine oxidases (containing TPQ or LTQ), electrons must be transferred to
      molecular oxygen by way of a redox-active copper ion in the protein.

PMID- 9003355
TI  - Structural elucidation of XR586, a peptaibol-like antibiotic from Acremonium
      persicinum.
AB  - A novel peptide, XR586, has been isolated from fermentations of Acremonium
      persicinum (Xenova culture collection number X21488). The structure of XR586 has
      been elucidated by means of NMR spectroscopy, electrospray and fast-atom
      bombardment MS, derivatization and enzymic digestion. It has been shown to be
      helical by CD measurements. XR586 shows many structural and conformational
      features in common with peptaibols, particularly the zervamicins. Peptaibol
      antibiotics are peptides, typically of 15-20 residues, containing a large
      proportion of alpha-aminoisobutyric acid (Aib) residues. These peptides adopt a
      helical conformation in solution and display anti-bacterial and toxic properties
      due to their ability to form pores in membranes. However, while XR586 contains
      several Aib residues, it lacks a terminal phenylalaninol and terminates in the
      sequence Phe-Gly. The lack of reduction of the penultimate residue at the C
      terminus may indicate that this step is normally at the end of the biosynthetic
      pathway of peptaibols and occurs with cleavage of Gly. The 1H chemical shift
      assignments of XR586 are reported in Supplementary Publication SUP 50179 (3
      pages), which has been deposited at the British Library Document Supply Centre,
      Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be
      obtained on the terms indicated in Biochem. J. (1996) 313, 9 ("Deposition of
      data').

PMID- 9003357
TI  - Lactase phlorhizin hydrolase turnover in vivo in water-fed and colostrum-fed
      newborn pigs.
AB  - We have estimated the synthesis rates in vivo of precursor and brush-border (BB)
      polypeptides of lactase phlorhizin hydrolase (LPH) in newborn pigs fed with water
      or colostrum for 24h post partum. At the end of the feeding period, piglets were
      anaesthetized and infused intravenously for 3h with L-[4-3H]- phenylalanine.
      Blood and jejunal samples were collected at timed intervals. The precursor and BB
      forms of LPH were isolated from jejunal mucosa by immunoprecipitation followed by
      SDS/PAGE, and their specific radioactivity in Phe determined. The kinetics of
      precursor and BB LPH labelling were analysed by using a linear compartmental
      model. Immunoisolated LPH protein consisted of five polypeptides [high-mannose
      LPH precursor (proLPHh), complex glycosylated LPH precursor (proLPHe),
      intermediate complex glycosylated LPH precursor (proLPH1i) and two forms of BB
      LPH]. The fractional synthesis rate (Ks) of proLPHh and proLPHc (approx. 5%/min)
      were the same in the two groups but the absolute synthesis rate (in arbitrary
      units, min-1) of proLPHh in the colostrum-fed animals was twice that of the water
      fed animals. The Ks values of proLPHi polypeptides were significantly different
      (water-fed, 3.89%/min; colostrum-fed, 1.6%/min), but the absolute synthesis rates
      did not differ. The Ks of BB LPH was not different between experimental treatment
      groups (on average 0.037%/min). However, the proportion of newly synthesized
      proLPHh processed to BB LPH was 48% lower in colostrum-fed than in water-fed
      animals. We conclude that in neonatal pigs, the ingestion of colostrum stimulates
      the synthesis of proLPHh but, at least temporarily, disrupts the processing of
      proLPH polypeptides to the BB enzyme.

PMID- 9003356
TI  - The binding of cholesterol and bile salts to recombinant rat liver fatty acid
      binding protein.
AB  - The physiological role of liver fatty acid-binding protein (L-FABP) has yet to be
      clarified. An important feature of this member of the family of intracellular
      lipid-binding proteins is the wide range of compounds that have been identified
      as potential physiological ligands. By using recombinant L-FABP, the binding of
      cholesterol, bile salts and their derivatives has been investigated under
      conditions that allow a direct comparison of the binding affinities of these
      ligands for fatty acids. The results demonstrate an inability of L-FABP to bind
      cholesterol, although the anionic derivative, cholesteryl sulphate, will bind
      under similar assay conditions. Of the bile salts examined, lithocholate and
      taurolithocholate sulphate showed the greatest binding to L-FABP. It is proposed
      that an important function of L-FABP is to bind certain physiological amphipathic
      anions, thus preventing the "free' concentrations of these compounds from
      exceeding their critical micelle concentration, which could result in cell
      damage.

PMID- 9003359
TI  - Feedback repression of ornithine decarboxylase synthesis mediated by antizyme.
AB  - The induction of antizyme by spermidine and the resulting enhancement of
      ornithine decarboxylase (ODC) degradation have been well studied; however, little
      is known about the mechanism whereby elevated spermidine levels decrease
      synthesis of the polyamine biosynthetic enzyme. To evaluate the relative
      contribution of inhibited synthesis, as distinct from enhanced degradation of
      ODC, spermidine levels were manipulated in a variant cell line that overproduces
      a stable form of ODC. Spermidine did not selectively inhibit ODC synthesis in
      these variant cells, supporting the concept that spermidine diminishes ODC
      synthesis in normal cells owing to enhanced degradation of the protein in the
      presence of elevated antizyme levels. This model was further investigated in
      vitro by use of rabbit reticulocyte lysate, which catalyses simultaneous ODC mRNA
      translation and antizyme-stimulated degradation of ODC protein. Antizyme strongly
      repressed the incorporation of labelled amino acids into normal rat ODC.
      Unexpectedly it also diminished the apparent translation of ODC mRNA species
      coding for enzyme forms that are not destabilized by the post-translational
      addition of antizyme. The effect of antizyme on ODC translation was not observed
      in wheatgerm extract, in which there is no antizyme-induced degradation. Further,
      deletion of a short segment of antizyme necessary for the destabilization of ODC
      (amino acid residues 113-118) resulted in a form that bound ODC but did not
      diminish its apparent translation. These results suggest that the co
      translational addition of antizyme to ODC results in a complex that is different
      from, and innately less stable than, that formed when antizyme is added post
      translationally.

PMID- 9003358
TI  - Regulation of tyrosine aminotransferase gene expression by glucocorticoids in
      quiescent and regenerating liver.
AB  - Following 70% hepatectomy, the induction of tyrosine amino-transferase mRNA by
      glucocorticoids was marginal at 1.5 h, significantly impaired between 3 and 8 h
      and, at 16 h post-hepatectomy, reached a value approx. 5-fold the basal level,
      similar to the level observed in quiescent liver. The fold induction of the mRNA
      was accounted for by a similar fold activation of transcription of the gene by
      glucocorticoids in regenerating but not in quiescent liver; in the latter,
      activation of transcription was marginal in spite of glucocorticoid-induced
      hypersensitivity to cleavage by DNase I at the glucocorticoid-dependent enhancer
      of the gene. The possibility that in quiescent liver glucocorticoids act at a
      transcriptional step beyond initiation, increasing the rate of elongation or
      overcoming a blockage in elongation, was excluded. However, a similar fold
      induction was determined for total and nuclear tyrosine aminotransferase mRNA in
      the presence of glucocorticoids, suggesting that in quiescent liver
      glucocorticoids promote efficient maturation of the tyrosine aminotransferase
      primary transcript. Thus a glucocorticoid-induced nuclear post-transcriptional up
      regulation apparently compensates for impaired activation of transcription of the
      tyrosine aminotransferase gene by glucocorticoids in quiescent liver.

PMID- 9003360
TI  - Recognition of subsets of the mammalian A/B-type core heterogeneous nuclear
      ribonucleoprotein polypeptides by novel autoantibodies.
AB  - The structurally related A/B-type core heterogeneous nuclear ribonucleoprotein
      (hnRNP) polypeptides of 34-39 kDa (A1, A2, B1 and B2) belong to a family of RNA
      binding proteins that are major components of 40 S hnRNP complexes. By two
      dimensional gel electrophoresis and peptide mapping analysis we compared each
      member of the A/B-type core proteins in the human and rat liver cells. This
      comparison revealed the unique presence in rat cells of major protein species,
      referred to as mBx polypeptides, that appeared as three charge isoforms at a
      position corresponding to the minor HeLa B1b protein spot. In addition, clear
      differences in the ratios of the A1 polypeptide to the A1b isoform were observed.
      The detection, in sera of patients with rheumatic autoimmune diseases, of two
      novel autoantibody specificities, one recognizing solely B2 protein and the
      second both the B2 and mBx polypeptides, helped to identify mBx proteins as new
      A/B-type hnRNP components, immunologically related to B2 protein. A common
      immunoreactive V8 protease peptide of approx. 17 kDa has been identified in B2
      and mBx hnRNP polypeptides. mBx protein species are identified in cells of murine
      origin, and have a ubiquitous tissue distribution and developmental appearance.

PMID- 9003361
TI  - Subunit VII of ubiquinol:cytochrome-c oxidoreductase from Neurospora crassa is
      functional in yeast and has an N-terminal extension that is not essential for
      mitochondrial targeting.
AB  - cDNA clones encoding subunit VII of the Neurospora crassa bc1 complex
      (ubiquinol:cytochrome-c oxidoreductase), which is homologous with subunit VIII of
      the complex from yeast (encoded by QCR8), were identified on the basis of
      functional complementation of a yeast QCR8 deletion strain. The clones contain an
      open reading frame encoding a protein with a calculated molecular mass of 11.8
      kDa. The N-terminal eight residues of the amino acid sequence deduced from the
      cDNA clones are absent from the mature protein, as revealed by direct sequencing
      of the isolated protein. To investigate the potential role of the N-terminal
      octapeptide in mitochondrial targeting, constructs were made encoding the
      precursor and the mature form of subunit VII from Neurospora. Incubation of
      isolated mitochondria with the two proteins revealed that the N-terminal
      extension of the precursor is removed on import. However, the presequence does
      not encode information for targeting, as the proteins encoded by both constructs
      can be imported into isolated mitochondria with equal efficiency. In contrast,
      the octapeptide seems to have functional importance: the defect in the yeast qcr8
      null mutant is not complemented on transformation with the construct encoding
      mature subunit VII from N. crassa in a single-copy plasmid. We therefore
      speculate that the N-terminal extension plays a role in intramitochondrial
      sorting of N. crassa subunit VII. This is supported by the fact that the subunit
      VII precursor is processed by a protease other than the general mitochondrial
      processing peptidase. Interestingly, the presequence of N. crassa subunit VII has
      an amino acid composition similar to the octapeptides cleaved off by the
      mitochondrial intermediate peptidase.

PMID- 9003362
TI  - Modulation of neutral protease expression in human mesangial cells by
      hyperglycaemic culture.
AB  - We report on the effect of prolonged hyperglycaemic (11 and 30 mM D-glucose)
      culture conditions on human mesangial cell matrix metalloproteinases (MMPs),
      plasminogen activators and their inhibitors. The results indicate that
      hyperglycaemic conditions modulate the potential proteolytic activity of the
      enzymes secreted by confluent cultures of these cells. Gelatinase A (MMP-2)
      activity was always higher in cultures maintained under hyperglycaemic than under
      normoglycaemic conditions (4 mM D-glucose). In contrast, gelatinase B (MMP-9)
      activity was decreased under the same conditions. Matrilysin (MMP-7) activity was
      decreased by up to 100% under hyperglycaemic conditions. Reverse transcriptase
      PCR and Western-blotting analyses indicate that in all cases both the transcripts
      and the protein level were correlated with enzymic activity. One tissue inhibitor
      of metalloproteinases, TIMP-2, was barely detectable under hyperglycaemic
      conditions (30 mM D-glucose). In contrast, TIMP-1 increased during the initial 2
      weeks of culture in hyperglycaemic conditions and remained elevated to the end of
      the experiment (4 weeks). Under normoglycaemic conditions TIMP-1 decreased after
      2 weeks of culture. Hyperglycaemic conditions also decreased markedly the
      activity of tissue plasminogen activator (t-PA). This seemed to be due to
      increased synthesis of its inhibitor, plasminogen activator inhibitor 1, under
      these conditions rather than to decreased expression of the t-PA enzyme.

PMID- 9003364
TI  - Anabaena flos-aquae and other cyanobacteria possess diadenosine 5',5"'-P1,P4
      tetraphosphate (Ap4A) phosphorylase activity.
AB  - Diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) phosphorylase, previously only
      known in lower eukaryotes, has been detected in extracts of the cyanobacteria
      Anabaena flos-aquae, Anabaena variabilis and Synechococcus sp. The 32 kDa enzyme
      was partially purified from A. flos-aquae and separated from a 23 kDa hydrolytic
      activity. It had a pH optimum of 9.5 and required a bivalent cation for activity:
      Mg2+, Mn2+, Ca2+, Co2+ or Zn2+. Diadenosine tri-, tetra- and penta-phosphates
      were all effective substrates (relative rates 0.85, 1.00 and 0.27 respectively),
      while the hexaphosphate was a poor substrate and the diphosphate was inactive.
      ADP was always one of the products of phosphorolysis. Arsenate and vanadate could
      substitute for phosphate (relative rates 1.80, 2.25 and 1.00 respectively), but
      tungstate and sulphate could not. Chromate and molybdate were poor substrates. A
      search of the GenBank non-redundant database revealed a putative Ap4A
      phosphorylase gene in the cyanobacterium Synechocystis sp. The gene showed
      significant blocks of identity/similarity with yeast Ap4A phosphorylases I and
      II, particularly the latter.

PMID- 9003363
TI  - ADP-ribosylation factor 1-regulated phospholipase D activity is localized at the
      plasma membrane and intracellular organelles in HL60 cells.
AB  - ADP-ribosylation factor (ARF), a small GTPase required for vesicle formation, has
      been identified as an activator of phospholipase D (PLD), thus implying that PLD
      is localized at intracellular organelles. HL60 cells were prelabelled with
      [14C]acetate for 72 h and, after disruption, fractionated on a linear sucrose
      gradient. ARF1-regulated PLD activity in each fraction was assessed by
      measurement of phosphatidylethanol production. Two peaks of activity were
      identified, coincident with markers for Golgi/endoplasmic reticulum/granules
      (endomembranes) and plasma membrane respectively. Analysis of the fractions using
      exogenous phosphatidylcholine as substrate confirmed the presence of ARF1
      dependent PLD activity in endomembranes and plasma membrane, and also identified
      an additional activity in the cytosol. In formyl-Met-Leu-Phe-stimulated cells,
      PLD activity as assessed by phosphatidylethanol formation was also associated
      with both the plasma membrane and endomembranes. Since ARF1-regulated PLD
      activity requires phosphatidylinositol 4,5-bisphosphate (PIP2), the distributions
      of inositol lipids and the kinases responsible for lipid phosphorylation were
      examined. PIP2 was highly enriched at the plasma membrane, whereas
      phosphatidylinositol (PI) and phosphatidylinositol 4-phosphate (PI4P), the
      precursors for PIP2 synthesis, were found predominantly at endomembranes. The
      distribution of PI 4-kinase and PI4P 5-kinase activities confirmed the plasma
      membrane as the major site of PIP2 production. However, endomembranes possessed
      substantial PI 4-kinase activity and some PI4P 5-kinase activity, illustrating
      the potential for PIP2 synthesis. It is concluded that:(1) ARF1-regulated PLD
      activity is localized at endomembranes and the plasma membrane, (2) PIP2 is
      available at both membrane compartments to function as a cofactor for ARF
      regulated PLD, and (3) in intact cells, formyl-Met-Leu-Phe stimulates PLD
      activity at endomembranes as well as plasma membrane.

PMID- 9003365
TI  - Biochemical characterization and deletion analysis of recombinant human protein
      phosphatase 2C alpha.
AB  - The use of protein phosphatase inhibitors has been instrumental in defining the
      intracellular roles of protein phosphatase 1 (PP1), PP2A and PP2B. Identification
      of the role of PP2C in vivo has been hampered, in part, by the unavailability of
      specific inhibitors. In order to facilitate the identification of novel and
      specific inhibitors of PP2C by random screening of compounds, and to further
      characterize this enzyme at the molecular level by site-directed mutagenesis and
      X-ray crystallography, we have expressed active recombinant human PP2C alpha
      (rPP2C alpha) in Escherichia coli. Biochemical characterization of rPP2C alpha
      showed that it could hydrolyse p-nitrophenyl phosphate (pNPP) although, in
      contrast with native PP2C, this was not stimulated by Mg2+. As with native PP2C,
      okadaic acid failed to inhibit rPP2C alpha, whereas 50 mM NaF dramatically
      inhibited its activity. An alignment of the amino acid sequence of AMP-activated
      protein kinase (AMPK) with those of other serine/threonine protein kinases around
      the regulatory phosphorylation site (subdomains VII-VIII) revealed a high degree
      of conservation. Phosphopeptides derived from this region of AMPK and containing
      the almost invariant threonine (Thr172 in AMPK) were found to be good substrates
      for rPP2C alpha. We also showed that rPP2C alpha can inactivate AMPK, but only in
      the presence of Mg2+. To define the regions of PP2C alpha important for catalytic
      activity, we expressed a number of truncated proteins based on the sequence and
      proposed domain structure of the PP2C alpha homologue from Paramecium
      tetraurelia. Deletion of 75 residues (9 kDa) from the C-terminus appeared to have
      little effect on the catalytic activity using pNPP, phosphopeptides or AMPK as
      substrates. This suggests that the residues important in catalysis lie elsewhere
      in the protein. A further deletion of the C-terminus led to a completely inactive
      and very poorly soluble protein.

PMID- 9003366
TI  - Point mutations in bovine opsin can be classified in four groups with respect to
      their effect on the biosynthetic pathway of opsin.
AB  - Expression in vitro with the recombinant baculovirus expression system showed
      correct biosynthesis and post-translational processing of "wild-type' bovine
      opsin with regard to translocation, glycosylation, palmitoylation and targeting.
      However, several of these processes were severely affected by point mutations.
      From the overall results of 16 mutants reported here, four groups were
      distinguished. One group significantly affected neither biosynthesis nor folding
      of opsin (D83N, P291A, A299C-V300A-P303G). A second group produced a truncated
      protein (R69H, Y301F), suggesting that these positions are essential for a
      correct translational process. A third group affected membrane translocation as
      well as glycosylation, which can be interpreted as interference with the function
      of a transfer signal. Substitutions at positions Glu-113, Glu-122, Glu-134, Arg
      135 and Lys-248 belong to this category. A fourth group induced structural
      changes in the protein that led to heterogeneous distribution in the plasma
      membrane (E113Q/D, W265F, Y268S). Taking any functional consequences of these
      mutations into consideration, it seems that point mutations can have mosaic
      effects and therefore should be examined at several levels (folding, targeting,
      functional parameters).

PMID- 9003367
TI  - Studies of the membrane topology of the rat erythrocyte H+/lactate cotransporter
      (MCT1).
AB  - 1. Hydrophobicity analysis of the monocarboxylate/proton cotransporter MCT1
      (lactate transporter) suggests a structure with 12 transmembrane (TM) segments,
      presumed to be alpha-helical. 2. A series of anti-peptide antibodies have been
      raised against regions of the MCT1 sequence, which each recognize a polypeptide
      of approx. 40 kDa in rat erythrocytes. The topology of rat MCT1 was investigated
      by studying the immunoreactive fragments derived from proteolytic digestion of
      the protein in intact rat erythrocytes and leaky membranes. 3. Reactivity with an
      anti-(C-terminus) antibody was prevented on treatment of leaky membranes, but not
      intact cells, with carboxypeptidase Y, indicating that the C-terminus of the
      protein is cytoplasmically disposed. 4. Treatment of intact cells in saline
      buffer with trypsin, chymotrypsin, bromelain and protease K (up to 1 mg/ml)
      resulted in no degradation of MCT1, indicating the absence of any large exposed
      extracellular loop. In a buffer of low ionic strength (containing sucrose),
      cleavage was observed with bromelain at an extracellular site, probably TM9/10.5.
      Treatment of leaky membranes with low (less than 100 micrograms/ml)
      concentrations of several proteases resulted in fragmentation of MCT1, reflecting
      cleavage at the cytoplasmic face of the membrane. These treatments generated N
      terminal fragments of apparent molecular mass approx. 17-19 kDa that were
      resistant to further degradation. The epitopes for the TM6/7 and C-terminal
      antibodies were either lost from the membrane or destroyed under most of these
      conditions, indicating that these regions of the protein are located in the
      cytoplasm. 6. More detailed structural prediction analysis of MCT-related
      sequences was made assuming the constraints placed upon the possible arrangements
      by the experimental data outlined above. This analysis provided additional strong
      evidence for the 12-TM-segment model, with cytoplasmic N- and C-terminal ends and
      a large internal loop between TM6 and TM7. The predicted helices were assigned
      moments of hydrophobicity and residue substitution; for a number of TM segments
      this permitted the prediction of the sides of the helix that faced membrane lipid
      and the interior of the protein.

PMID- 9003368
TI  - Adenosylcobalamin-dependent glutamate mutase: properties of a fusion protein in
      which the cobalamin-binding subunit is linked to the catalytic subunit.
AB  - Adenosylcobalamin-dependent glutamate mutase (EC 5.4.99.1) from Clostridium
      tetanomorphum comprises two protein components, MutE and MutS. The formation of
      the holoenzyme is a kinetically complex process that involves the co-operative
      association of MutS, MutE and adenosylcobalamin. The MutS portion of the
      cobalamin-binding site is conserved within a group of adenosylcobalamin-dependent
      enzymes that catalyse similar isomerizations. However, in contrast with glutamate
      mutase, in these other enzymes the cobalamin-binding region represented by MutS
      is present as a C-terminal domain. We have investigated the effect on the
      structural and kinetic properties of glutamate mutase of linking MutS to the C
      terminus of MutE. Kinetic analysis of this protein, MutES, showed, unexpectedly,
      that enzyme activity was still co-operatively dependent on protein concentration.
      The Km for L-glutamate was unchanged from the wild type, whereas Vmax was
      decreased to approx. one-thirtieth and the Km for coenzyme increased approx. 10
      fold. Investigation of the quaternary structure of MutES by equilibrium ultra
      centrifugation indicated that the protein existed in equilibrium between
      monomeric and dimeric forms. Thus linking MutE and MutS together seems to
      substantially weaken the contacts that are responsible for the dimerization of
      MutE. The two domains of the MutES monomer seem unable to communicate, so that
      active enzyme is formed by the intermolecular association of two MutES subunits
      in a co-operative manner.

PMID- 9003369
TI  - Protein kinase C in cultured human placental trophoblasts: identification of
      isoforms and role in cAMP signalling.
AB  - The protein kinase C (PKC) superfamily is a family of serine/threonine kinases
      involved in the regulation of many cell functions. The objective of the present
      work was to identify the PKC isoenzymes present in human placental trophoblasts
      and to compare their relative responses to acute and chronic phorbol 12-myristate
      13-acetate (PMA) treatment. In addition, the effect of PMA treatment on ligand
      stimulated cAMP production was determined. In total extracts prepared from
      cultured or freshly purified trophoblasts, PKC isoforms alpha, epsilon and zeta
      were detected. Following acute treatment with PMA, PKC alpha and PKC epsilon were
      translocated from the cytosol to the particulate fraction. Prolonged treatment
      (up to 36 h) with PMA resulted in the temporal down-regulation of PKC alpha and
      PKC epsilon. PKC zeta did not respond to either acute or chronic treatment with
      PMA. An acute 10 min treatment of the cells with PMA (10(-10)-10(-6) M) enhanced
      isoprenaline- and adrenaline-stimulated cAMP production. An enhanced response was
      observed at all concentrations of isoprenaline tested (10(-9)-10(-4) M),
      suggesting an increased capacity to respond. The acute PMA effect was evident
      within 2 min and near maximal by 5 min. The acute response to PMA was lost in
      cells where PKC was down-regulated by prior PMA treatment. Epidermal growth
      factor, a potential ligand for the activation of PKC in trophoblasts, enhanced
      isoprenaline-stimulated cAMP production. In summary, activation of PMA-responsive
      PKCs (PKC alpha or PKC epsilon) appears to enhance ligand-stimulated cAMP
      production in trophoblasts. This may be a physiologically important example of
      'cross-talk' between various signalling pathways in human placental trophoblasts.

PMID- 9003370
TI  - The effect of chloroform on mitochondrial energy transduction.
AB  - The effect of chloroform on mitochondrial respiration with succinate was
      investigated by applying the method of Brand, Chien and Diolez [(1994) Biochem.
      J. 297, 27-29] to examine whether chloroform causes redox slip (fewer protons
      pumped per electron transferred) during mitochondrial electron transport.
      N,N,N',N'-Tetramethyl-p-phenylenediamine (TMPD), which lowers H+/O (the number of
      protons pumped to the external medium by the electron transport complexes per
      oxygen atom consumed) by altering the electron flow pathway, was investigated for
      comparison. Non-phosphorylating mitochondria that had been treated with 350
      microM TMPD or 30 mM chloroform were titrated with malonate in the presence of
      submaximal concentrations of the uncoupler carbonyl cyanide m
      chlorophenylhydrazone (CCCP). Linear relations between CCCP-induced extra
      respiration and protonmotive force were obtained. These results showed that there
      was no measurable protonmotive force-dependent or rate-dependent slip in
      mitochondria treated with either TMPD or chloroform. However, both TMPD and
      chloroform seemed to decrease H+/O in a manner independent of protonmotive force
      and rate. The relationship between non-phosphorylating respiration and
      protonmotive force was simulated in mitochondria of which 25% of the total
      population were assumed to have been broken. The simulation showed that the
      apparent decrease in H+/O on the addition of TMPD or chloroform to mitochondria
      could be in principle accounted for by breakage. Assays of mitochondrial breakage
      (ATP hydrolysis in the presence of atractyloside and oxidation of exogenous NADH)
      showed that chloroform broke mitochondria but TMPD did not. We conclude that
      chloroform changes the measured H+/O as an artifact by causing mitochondrial
      breakage and does not cause measurable redox slip, whereas TMPD genuinely lowers
      H+/O.

PMID- 9003371
TI  - Evidence for regulated dimerization of cell-cell adhesion molecule (C-CAM) in
      epithelial cells.
AB  - C-CAM is a Ca(2+)-independent cell adhesion molecule (CAM) belonging to the
      immunoglobulin superfamily. Addition of chemical cross-linkers to isolated rat
      liver plasma membranes, intact epithelial cells and purified preparations of C
      CAM stabilized one major C-CAM-containing product whose apparent molecular mass
      was approximately twice that of the C-CAM monomer. The failure to detect
      additional proteins after cleavage of the cross-linked species demonstrated that
      C-CAM exists as non-covalently linked dimers both in solution and on the cell
      surface. Dimerization occurred to the same extent in adherent monolayers and in
      single cell populations, indicating that dimer formation was the result of cis
      interactions within the membranes of individual cells. Using isoform-specific
      anti-peptide antibodies, both C-CAM1 and C-CAM2 were found to be involved in
      dimerization, forming predominantly homo-dimeric species. Both calmodulin and
      Ca2+ ionophore modulated the level of dimer formation, suggesting a role for
      regulated self-association in the functional activity of C-CAM.

PMID- 9003372
TI  - Reducing sugars trigger oxidative modification and apoptosis in pancreatic beta
      cells by provoking oxidative stress through the glycation reaction.
AB  - Several reducing sugars brought about apoptosis in isolated rat pancreatic islet
      cells and in the pancreatic beta-cell-derived cell line HIT. This apoptosis was
      characterized biochemically by inter-nucleosomal DNA cleavage and morphologically
      by nuclear shrinkage, chromatin condensation and apoptotic body formation. N
      Acetyl-L-cysteine, an antioxidant, and aminoguanidine, an inhibitor of the
      glycation reaction, inhibited this apoptosis. We also showed directly that
      proteins in beta-cells were actually glycated by using an antibody which can
      specifically recognize proteins glycated by fructose, but not by glucose.
      Furthermore, fluorescence-activated cell sorting analysis using
      dichlorofluorescein diacetate showed that reducing sugars increased intracellular
      peroxide levels prior to the induction of apoptosis. Levels of carbonyl, an index
      of oxidative modification, and of malondialdehyde, a lipid peroxidation product,
      were also increased. Taken together, these results suggest that reducing sugars
      trigger oxidative modification and apoptosis in pancreatic beta-cells by
      provoking oxidative stress mainly through the glycation reaction, which may
      explain the deterioration of beta-cells under conditions of diabetes.

PMID- 9003373
TI  - Post-translational peptide bond formation during concanavalin A processing in
      vitro.
AB  - Post-translational processing of concanavalin A (Con A) is complex, involving
      deglycosylation, proteolytic cleavage on the carboxy group side of asparagine
      residues and formation of a peptide bond de novo. This has been studied with the
      125I-labelled Con A glycoprotein precursor as a substrate for processing in
      vitro. Extracts of immature jackbean cotyledons and the commercially available
      purified preparation of asparaginylendo-peptidase were able to catalyse the above
      processes. The processing resulted in the conversion of the 33.5 kDa inactive
      glycoprotein precursor into an active lectin. Processing activity was maximal at
      approx. pH 5.5. Evidence to support processing at authentic sites was obtained by
      observation of the release of 125I at positions in the sequence where tyrosine
      residues were present.

PMID- 9003374
TI  - Insulin action in cultured human myoblasts: contribution of different signalling
      pathways to regulation of glycogen synthesis.
AB  - A key metabolic action of insulin is the stimulation of non-oxidative glucose
      utilization in skeletal muscle, by increasing both glucose uptake and glycogen
      synthesis. The molecular mechanism underlying this process has been investigated
      using a variety of experimental systems. We report here the use of cultured human
      myoblasts to study insulin control of glycogen synthesis in humans. In these
      cells insulin stimulates glycogen synthesis approx. 2.2-fold, associated with a
      similar activation of glycogen synthase (GS) which occurs within 5-10 min of the
      addition of insulin. Insulin also causes inactivation of glycogen synthase kinase
      3 (GSK-3) and activation of protein kinase B, both processes being sufficiently
      rapid to account for the effects of insulin on GS. Activation by insulin of the
      protein kinases p70s6K, p90s6K and extracellular signal-regulated kinase 2 (ERK2)
      is observed, but is significantly slower than the activation of GS. Selective
      inhibitors of the p70s6K pathway (rapamycin), the ERK2/p90s6K pathway (PD98059)
      and phosphatidylinositol 3-kinase (wortmannin) have been used to probe the
      contribution of these components to insulin signalling in human muscle.
      Wortmannin blocks activation of both glycogen synthesis and GS and inactivation
      of GSK-3. PD98059 is without effect on these events, while rapamycin is without
      effect on inactivation of GSK-3 but partially blocks activation of glycogen
      synthesis and GS. Taken together, these findings suggest that protein kinase B is
      responsible for the inactivation of GSK-3, but that an additional rapamycin
      sensitive mechanism may contribute to the activation of GS and stimulation of
      glycogen synthesis.

PMID- 9003375
TI  - Competitive inhibition of calcineurin phosphatase activity by its autoinhibitory
      domain.
AB  - Calcineurin (protein phosphatase 2B), a calmodulin- and calcium-dependent
      serine/threonine phosphatase, appears to be regulated by a C-terminal
      autoinhibitory domain. A 25 amino acid peptide derived from this domain inhibits
      calcineurin phosphatase activity in vitro. Here we show that a 97 amino acid
      fragment of the calcineurin A alpha C-terminus is approx. 8-fold more potent than
      the shorter peptide in calcineurin inhibition experiments. Mutation of an
      evolutionarily conserved Asp to Asn, previously shown to disrupt calcium
      dependent signalling and calcineurin regulation in T-lymphocytes, greatly reduced
      inhibition by the autoinhibitory domain in vitro. Kinetic analysis of wild-type
      and mutated autoinhibitory domains show that both are competitive inhibitors of
      calcineurin phosphatase activity with Ki values of 5.0 +/- 0.2 microM and 36.0 +/
      3.7 microM respectively. This suggests intrasteric regulation of calcineurin,
      with the autoinhibitory domains interacting at the active site of the enzyme. The
      competitive behaviour of the autoinhibitory domains contrasts with the mechanism
      of calcineurin inhibition by immunosuppressant-immunophilin complexes, which have
      been shown to bind to calcineurin at a region removed from the active site.

PMID- 9003376
TI  - Phorbol ester-sensitive phospholipase D is mainly localized in the endoplasmic
      reticulum of BHK cells.
AB  - The localization of phorbol ester-sensitive phospholipase D (PLD) in baby hamster
      kidney cells has been investigated by determining the subcellular distribution of
      the phosphatidylbutanol produced when the cells are incubated with phorbol 12
      myristate 13-acetate and n-butanol. Results derived by isolation of plasma
      membrane vesicles from intact cells or by subcellular fractionation on a sucrose
      density gradient suggest the PLD is specific for phosphatidylcholine and its
      primary site of action is not the plasma membrane but the endoplasmic reticulum.

PMID- 9003377
TI  - Role of the 3' untranslated region in the regulation of cytosolic glutathione
      peroxidase and phospholipid-hydroperoxide glutathione peroxidase gene expression
      by selenium supply.
AB  - Selenium is an essential nutrient and synthesis of selenoproteins is affected by
      limited selenium supply. During selenium deficiency there is a differential
      regulation of selenoprotein synthesis and gene expression; for example, there is
      a decrease in abundance of mRNA for cytosolic glutathione peroxidase (cGSH-Px)
      and a preservation of mRNA for phospholipid-hydroperoxide glutathione peroxidase
      (PHGSH-Px). This difference is not due to an alteration in the rate of
      transcription but might reflect differences in translation. The aim of the
      present work was to assess the role of cGSH-Px and PHGSH-Px 3' untranslated
      regions (UTRs) in the regulation of selenoprotein mRNA stability and translation
      by using H4-II-E-C3 cells transfected with different constructs containing a type
      I iodothyronine deiodinase-coding region linked to different selenoprotein mRNA
      3' UTRs. Translational efficiency results showed that the efficiency of the 3'
      UTRs in permitting selenocysteine incorporation is similar in selenium-replete
      conditions but, when selenium is limiting, the 3' UTR of cGSH-Px is less
      efficient than the 3' UTR of PHGSH-Px. The results suggest that the 3' UTR of
      these selenoprotein mRNA species influences their extent of translation when
      selenium levels are low. The different sensitivity of the 3' UTRs to selenium
      deficiency can explain the differential effect that selenium deficiency has on
      cGSH-Px and PHGSH-Px activity and mRNA levels, stability and translation. This
      might be partly responsible for channelling selenium for synthesis of PHGSH-Px
      rather than cGSH-Px.

PMID- 9003378
TI  - Lactoferrin regulates the activity of heparin proteoglycan-bound mast cell
      chymase: characterization of the binding of heparin to lactoferrin.
AB  - Rat mast cell protease 1 (RMCP-1) is a secretory granule serine protease
      (chymase) that is recovered in vivo in a macromolecular complex with heparin
      proteoglycan (PG). We have previously shown that heparin activates RMCP-1 and
      that RMCP-1, when bound to heparin PG, is largely resistant to inhibition by a
      variety of macromolecular protease inhibitors. In the search for alternative
      mechanisms in the regulation of RMCP-1 activity, we hypothesized that heparin
      antagonists, by interfering with the RMCP-1/heparin PG interaction, might
      influence the activity of heparin-bound mast cell chymase. In the present study,
      lactoferrin (LF), a heparin-binding protein, was assessed for RMCP-1 inhibiting
      activity. LF proved to decrease the activity of heparin PG-associated RMCP-1,
      although a portion of the enzyme activity was resistant to regulation. The
      mechanism of regulation was shown to involve the displacement of RMCP-1 from
      heparin PG, and LF caused an approx. 6-fold increase in the apparent Km of the
      RMCP-1-heparin PG complex for the chromogenic substrate S-2586. The interaction
      of LF with heparin was characterized. Pig mucosal heparin and endogenous heparin
      PG were equally effective in binding LF, whereas heparan sulphate bound with
      lower affinity. None of dermatan sulphate, chondroitin sulphate or hyaluronan
      were effective in binding LF. Further, the 6-O-, 2-O- and N-sulphate groups in
      heparin were of approximately equal importance for binding. Octasaccharides were
      the smallest heparin oligosaccharides showing significant binding to LF.

PMID- 9003379
TI  - Overexpression of phosphatidylethanolamine N-methyltransferase 2 in CHO-K1 cells
      does not attenuate the activity of the CDP-choline pathway for
      phosphatidylcholine biosynthesis.
AB  - Chinese hamster ovary (CHO) cells express only a trace amount of
      phosphatidylethanolamine N-methyltransferase (PEMT) activity. CHO cells make
      their phosphatidylcholine (PC) via the CDP-choline pathway. We investigated
      whether or not overexpression of PEMT2, an isoform of PEMT, in these cells would
      down-regulate the activity of the CDP-choline pathway. Transfection of CHO cells
      with PEMT2 cDNA behind the cytomegalovirus promoter resulted in a series of cell
      lines that overexpressed PEMT2. Phospholipid metabolism was characterized in cell
      lines that expressed a medium (281 pmol/min per mg of protein) and a high (1300
      pmol/min per mg of protein) level of PEMT activity. The expression of the
      regulated enzyme (CTP:phosphocholine cytidylyltransferase) in the CDP-choline
      pathway was increased, not decreased, in these cell lines as judged by immunoblot
      analysis and enzymic activity. Conversion of phosphatidylethanolamine to PC was
      enhanced in CHO cells that expressed PEMT2 activity. PC mass was not increased in
      the transfected compared with the control cells. The rate of PC catabolism made
      by either the CDP-choline or methylation pathways was unaffected by PEMT2
      expression. We conclude that expression of PEMT2 in CHO cells does not down
      regulate, but rather enhances, the expression of CTP:phosphocholine
      cytidylyltransferase.

PMID- 9003380
TI  - High-affinity binding of laurate to naturally occurring mutants of human serum
      albumin and proalbumin.
AB  - Binding of laurate (n-dodecanoate) to genetic variants of albumin or its
      proprotein and to normal albumin isolated from the same heterozygous carriers was
      studied by a kinetic dialysis technique at physiological pH. The first
      stoichiometric association constant for binding to proalbumin Lille (Arg-2-->His)
      and albumin (Alb) Roma (Glu321-->Lys) was increased to 126% and 136% respectively
      compared with that for binding to normal albumin, whereas the constant for Alb
      Maku (Lys541-->Glu) was decreased to 80%. In contrast, normal laurate-binding
      properties were found for as many as nine other albumin variants with single
      amino acid substitutions. Because the net charges of all these mutants were
      different from that of normal albumin, the results suggest that the examples of
      modified laurate binding are not caused by long-range electrostatic effects.
      Rather, the three positions mentioned are located close to different binding
      sites for the fatty acid anion. The most pronounced effect was observed for the
      glycosylated Alb Casebrook, the binding constant of which was decreased to 20%.
      Binding to the glycosylated Alb Redhill was also decreased, but to a smaller
      extent (68%). These decreases in binding are caused by partial or total blocking
      of the high-affinity site by the oligosaccharides, by the negative charges of the
      oligosaccharides, and/or by conformational changes induced by these bulky
      moieties. Laurate binding to two chain-termination mutants (Alb Catania and Alb
      Venezia) was normal, indicating that the C-terminus of albumin is not important
      for binding. By using different preparations of normal albumin as controls in the
      binding experiments, it was also possible to compare the effect of various
      methods for isolation and defatting on laurate binding.

PMID- 9003382
TI  - Influence of metal ions on substrate binding and catalytic activity of mammalian
      protein geranylgeranyltransferase type-I.
AB  - Protein geranylgeranyltransferase type-I (GGTase-I) transfers a geranylgeranyl
      group from the prenyl donor geranylgeranyl diphosphate (GGPP) to the cysteine
      residue of substrate proteins containing a C-terminal CaaX-motif (a sequence
      motif of proteins consisting of an invariant Cys residue fourth from the C
      terminus). The GGTase-I heterodimer contains one atom of zinc, and this metal is
      required for enzyme activity. In this regard, GGTase-I is similar to the related
      enzyme protein farnesyltransferase (FTase); the latter enzyme also requires Mg2+
      for activity. The current studies were undertaken in an attempt to explore
      further the role of bivalent metal ions in the activity of GGTase-I.
      Surprisingly, we found that GGTase-I and FTase have different metal requirements.
      Specifically, in marked contrast to FTase, GGTase-I does not require Mg2+ for
      activity. Direct binding assays, including a novel fluorescence-based technique,
      were employed to obtain quantitative information on the interaction of substrates
      with GGTase-I. Using these assays, we demonstrate that the Zn2+ in GGTase-I is
      required for peptide, but not for isoprenoid, substrate binding. Moreover,
      binding of GGPP protects GGTase-I from inactivation by zinc-chelating reagents;
      this protective effect is not seen with binding of peptide substrates. Metal
      substitution studies show that the Zn2+ in GGTase-I can be replaced by Cd2+, and
      that the Cd form of GGTase-I has altered specificity with regard to utilization
      of both peptide and isoprenoid substrates. The significance of these findings in
      relation to proposed mechanisms for the GGTase-I reaction is discussed.

PMID- 9003381
TI  - Interactions between organic anions, micelles and vesicles in model bile systems.
AB  - Biliary lipid secretion probably involves both 'micellization' and
      'vesiculization' of bile-canalicular membrane lipids. Several hydrophilic organic
      anions inhibit the secretion of lipids into the bile without altering bile salt
      secretion [Verkade, Vonk and Kuipers (1995) Hepatology 21, 1174-1189].
      Hydrophobic organic anions do not interfere with biliary lipid secretion. We
      investigated whether the organic-anion-induced inhibition of biliary lipid
      secretion in vivo could be attributed to inhibition of micellization, by the
      application of in vitro models of micellization. Carboxyfluorescein was entrapped
      in a self-quenching concentration in small unilamellar vesicles (SUV) composed of
      cholesterol/egg phosphatidylcholine (molar ratios 0, 0.2 and 0.5). Certain
      organic anions clearly affected the bile-salt-induced release of fluorescence
      from these SUV, reflecting interference with micellization. However, the effects
      of hydrophilic and hydrophobic organic anions did not correspond with their
      effects on biliary lipid secretion in vivo, irrespective of the bile salt species
      used (taurocholate, taurodeoxycholate or tauroursodeoxycholate) and of the lipid
      composition of the SUV. Ultracentrifugation and dynamic light-scattering studies
      indicated that organic anions do interact with bile salt/
      phosphatidylcholine/cholesterol mixed micelles, but that they do not inhibit
      micellization, for example by competing with phosphatidylcholine and/or
      cholesterol for incorporation into mixed micelles. In conclusion, the present in
      vitro data indicate that the in vivo mechanism of organic-anion-induced
      inhibition of biliary lipid secretion is not mediated by inhibition of
      micellization.

PMID- 9003383
TI  - The cytochrome c3 superfamily: amino acid sequence of a dimeric octahaem
      cytochrome c3 (M(r) 26,000) isolated from Desulfovibrio gigas.
AB  - Cytochrome c3 (M(r) 26000) isolated from Desulfovibrio gigas is a dimeric
      cytochrome consisting of two identical subunits of 109 amino acids, each of which
      contains four haem groups. On the basis of its amino acid sequence, this
      cytochrome clearly belongs to the cytochrome c3 superfamily, and will be
      classified in class III of the c-type cytochromes as defined by Ambler [(1980) in
      From Cyclotrons to Cytochromes (Robinson, A. B. and Kaplan, N. O., eds.), pp. 263
      279, Academic Press, London]. It contains ten cysteine and nine histidine
      residues in each subunit, and eight cysteines and eight histidines linked to the
      four haem groups were found to be invariant on alignment of all known cytochrome
      c3 sequences. Two intermolecular disulphide bridges have been determined between
      cysteine residues 5 and 46 of the two monomers. Cytochrome c3 (M(r) 26,000) from
      D gigas is clearly different from cytochrome c3 (M(r) 13,000) from the same
      strain, with which it shows only 27% sequence identity. Compared with cytochrome
      c3 (M(r) 26,000) from D. desulfuricans Norway, the three-dimensional structure of
      which has been determined, 26.95% of the residues have been conserved. In the
      enzyme from D. desulfuricans Norway, hydrophobic interactions have been described
      across the dimer interface. Residues involved in similar interactions seem to be
      well conserved in the equivalent D. gigas cytochrome. This sequence provides
      structural data to allow specification of this new subclass of polyhaem
      cytochromes. Furthermore, D. gigas cytochrome c3 (M(r) 26,000) is the first
      polyhaem cytochrome shown to contain two disulphide bridges linking two identical
      subunits, which could induce more rigid folding. The folding and the evolution of
      this family of polyhaem cytochromes are discussed.

PMID- 9003384
TI  - Trypsin stimulates proteinase-activated receptor-2-dependent and -independent
      activation of mitogen-activated protein kinases.
AB  - We have examined protease-mediated activation of the mitogen-activated protein
      (MAP) kinase cascade in rat aortic smooth-muscle cells and bovine pulmonary
      arterial fibroblasts. Exposure of smooth-muscle cells to trypsin evoked rapid and
      transient activation of c-Raf-1, MAP kinase kinase 1 and 2 and MAP kinase that
      was sensitive to inhibition by soybean trypsin inhibitor. The actions of trypsin
      were closely mimicked by the proteinase-activated receptor 2 (PAR-2)-activating
      peptide sequence SLIGRL but not LSIGRL. Peak MAP kinase activation in response to
      both trypsin and SLIGRL was also dependent on concentration, with EC50 values of
      12.1 +/- 3.4 nM and 62.5 +/- 4.5 microM respectively. Under conditions where MAP
      kinase activation by SLIGRL was completely desensitized by prior exposure of
      smooth-muscle cells to the peptide, trypsin-stimulated MAP kinase activity was
      markedly attenuated (78.9 +/- 15.1% desensitization), whereas the response to
      thrombin was only marginally affected (16.6 +/- 12.1% desensitization). Trypsin
      and SLIGRL also weakly stimulated the activation of the MAP kinase homologue p38
      in smooth-muscle cells without any detectable activation of c-Jun N-terminal
      kinase. Strong activation of the MAP kinase cascade and modest activation of p38
      by trypsin were also observed in fibroblasts, although in this cell type these
      effects were not mimicked by SLIGRL nor by the thrombin receptor-activating
      peptide SFLLRNPNDKYEPF. Reverse transcriptase-PCR analysis confirmed the presence
      of PAR-2 mRNA in smooth-muscle cells but not fibroblasts. Our results suggest
      that in vascular smooth-muscle cells, trypsin stimulates the activation of the
      MAP kinase cascade relatively selectively, in a manner consistent with an
      interaction with the recently described PAR-2. Activation of MAP kinase by
      trypsin in vascular fibroblasts, however, seems to be independent of PAR-2 and
      occurs by an undefined mechanism possibly involving novel receptor species.

PMID- 9003385
TI  - The characterization of endosomal insulin degradation intermediates and their
      sequence of production.
AB  - Insulin degradation within isolated rat liver endosomes was studied in vitro with
      the aid of three 125I-insulin isomers specifically labelled at tyrosine (A14, B16
      and B26). Chloroquine and 1,10-phenanthroline were used to minimize insulin
      proteolysis during endosome preparation, whereas the manipulation of endosomal
      processing of insulin in vitro by Co2+ ions (to activate) and 1,10-phenanthroline
      (to inhibit) permitted the study of degradation intermediates and their time
      dependent production. Structural and kinetic analysis of intermediates isolated
      from both intra- and extra-endosomal compartments allowed the determination of
      major cleavage sites and the probable sequence of proteolytic events. It was
      found that 125I-tyrosine is the ultimate labelled degradation product of all iodo
      insulin isomers, suggesting that endosomal proteases are able to degrade insulin
      to the level of its constituent amino acids. 125I-tyrosine was also the only
      radiolabelled product able to cross the endosomal membrane. Intra-endosomal
      insulin degradation proceeds via two inter-related cleavage routes after
      metalloendoprotease cleavage of the B-chain. One pathway results from an initial
      cleavage in the centre region of the B-chain (B7-19), probably at B14-15, whereas
      the major route results from a cleavage at B24-25. B24-25 cleavage removes the B
      chain C-terminal hexapeptide (B25-30), which is subsequently cleaved by an
      aminopeptidase activity to produce first the pentapeptide B26-30 and then 125I
      tyrosine. The isolation of intact radiolabelled A-chain from the degradation of
      125I-[A14]-insulin suggests that further degradation of proteolytic intermediates
      containing cleaved B-chain proceeds via interchain disulphide reduction. The A
      chain is then processed by several cleavages, one of which occurs at A13-14.

PMID- 9003386
TI  - Elevated intracellular calcium concentration increases secretory processing of
      the amyloid precursor protein by a tyrosine phosphorylation-dependent mechanism.
AB  - Secretory cleavage of the amyloid precursor protein (APP), a process that
      releases soluble APP derivatives (APPs) into the extracellular space, is
      stimulated by the activation of muscarinic receptors coupled to phosphoinositide
      hydrolysis. The signalling pathways involved in the release process exhibit both
      protein kinase C- and protein tyrosine phosphorylation-dependent components
      [Slack, Breu, Petryniak, Srivastava and Wurtman (1995) J. Biol. Chem. 270, 8337
      8344]. The possibility that elevations in intracellular Ca2+ concentration
      initiate the tyrosine phosphorylation-dependent release of APPs was examined in
      human embryonic kidney cells expressing muscarinic m3 receptors. Inhibition of
      protein kinase C with the bisindolylmaleimide GF 109203X decreased the carbachol
      evoked release of APPs by approx. 30%, as shown previously. The residual response
      was further decreased, in an additive manner, by the Ca2+ chelator EGTA, or by
      the tyrosine kinase inhibitor tyrphostin A25. The Ca2+ ionophore, ionomycin, like
      carbachol, stimulated both the release of APPs and the tyrosine phosphorylation
      of several proteins, one of which was identified as paxillin, a component of
      focal adhesions. The effects of ionomycin on APPs release and on protein tyrosine
      phosphorylation were concentration-dependent, and occurred over similar
      concentration ranges; both effects were inhibited only partly by GF 109203X, but
      were abolished by EGTA or by tyrosine kinase inhibitors. The results demonstrate
      for the first time that ionophore-induced elevations in intracellular Ca2+ levels
      elicit APPs release via increased tyrosine phosphorylation. Part of the increase
      in APPs release evoked by muscarinic receptor activation might be attributable to
      a similar mechanism.

PMID- 9003388
TI  - 2-mercaptoethanol restores the ability of nuclear factor kappa B (NF kappa B) to
      bind DNA in nuclear extracts from interleukin 1-treated cells incubated with
      pyrollidine dithiocarbamate (PDTC). Evidence for oxidation of glutathione in the
      mechanism of inhibition of NF kappa B by PDTC.
AB  - The metal chelator and anti-oxidant pyrollidine dithiocarbamate (PDTC) has been
      used extensively in studies implicating reactive oxygen intermediates in the
      activation of nuclear factor kappa B (NF kappa B). In agreement with other
      studies, we have shown that PDTC inhibits NF kappa B activation in response to
      the pro-inflammatory cytokines interleukin 1 (IL1) and tumour necrosis factor
      (TNF). However, we have found that the inhibition was reversed by treatment of
      inhibited nuclear extracts with the reducing agent 2-mercaptoethanol. This was
      observed in extracts prepared from IL1-treated EL4.NOB-1 thymoma cells and TNF
      treated Jurkat E6.1 lymphoma cells. These results suggested that the inhibition
      was caused by oxidation of NF kappa B on a sensitive thiol, possibly on the p50
      subunit (which was detected in NF kappa B complexes in both cell types), and not
      by inhibition of the activation pathway. The possibility that PDTC was acting as
      a pro-oxidant was therefore investigated. PDTC caused an increase in oxidized
      glutathione, suggesting that it acts as an oxidizing agent in the cells tested
      rather than as an anti-oxidant. Similar results were obtained with diamide, a
      compound designed to oxidize glutathione. Finally, an increase in the ratio of
      oxidized to reduced glutathione was shown to inhibit NF kappa B-DNA binding in
      vitro. On the basis of these results we suggest that, while NF kappa B activation
      is unaffected by PDTC, DNA binding is inhibited through a mechanism involving a
      shift towards oxidizing conditions, and that this is the mechanism of action of
      both PDTC and diamide in the cells tested here.

PMID- 9003387
TI  - Cross-linking of the high-affinity IgE receptor induces the expression of cyclo
      oxygenase 2 and attendant prostaglandin generation requiring interleukin 10 and
      interleukin 1 beta in mouse cultured mast cells.
AB  - When mouse bone marrow-derived mast cells (BMMC) developed in interleukin (IL)-3
      were activated with IgE and antigen (IgE/antigen) in the presence of both IL-10
      and IL-1 beta, two sequential phases of prostaglandin (PG)D2 generation were
      elicited, in which the first phase occurred by 1 h and the second phase from 2 to
      10 h. The delayed phase of PGD2 generation was accompanied by a marked induction
      of cyclo-oxygenase (COX)-2 mRNA, which reached a peak at 1-2 h, followed by that
      of its protein from 2-10 h, with a peak at 5 h. The immediate phase of PGD2
      generation was completely abrogated by the irreversible inhibition of pre
      existing COX-1 by aspirin pretreatment, whereas the delayed phase of PGD2
      generation was almost undetectable in the presence of the COX-2 inhibitor NS-398.
      A detailed analysis of the individual effects of IgE/antigen, IL-10 and IL-1 beta
      on COX-2 expression revealed that IgE/antigen and IL-10 each initiated and
      stabilized COX-2 mRNA expression, leading to an increase in the expression of its
      protein. Conversely, IL-1 beta stabilized the COX-2 protein without affecting its
      mRNA level. The induction of COX-2 by IgE/antigen with IL-10 and IL-1 beta
      preceded the induction of transcripts for endogenous cytokines such as IL-6, IL-1
      beta and IL-10. The inhibition of PGD2 generation by indomethacin did not affect
      the induction of COX-2 or these cytokines. Thus the two major delayed-phase
      responses of BMMC after IgE-dependent activation, namely COX-2-dependent PGD2
      generation and cytokine production, are regulated independently.

PMID- 9003389
TI  - Phosphorylation site specificity of the CDC2-related kinase PITALRE.
AB  - PITALRE is a human protein kinase belonging to the cell division cycle 2 (CDC2)
      kinase family, and is the catalytic subunit of a multimeric complex that contains
      several cellular proteins. PITALRE complexes from several cell lines and tissues
      phosphorylate retinoblastoma protein and myelin basic protein (MBP). In the
      present work, we have found that MBP is phosphorylated by PITALRE complexes on
      both Ser and Thr residues. Two different antibodies raised to PITALRE purified
      virtually identical kinase activities, as analysed by MBP phosphopeptide mapping
      and phosphoamino acid analysis. We have identified the proline-directed residue
      Ser-162 of MBP as a major phosphorylation site for PITALRE. In addition, our
      results suggest that one of the two MBP proline-directed threonine residues, Thr
      97, is also selectively phosphorylated by PITALRE. These data, together with
      analysis of different peptide substrates derived from sites on MBP that are
      phosphorylated by PITALRE, indicate that PITALRE is a Ser/Thr proline-directed
      kinase. In addition, our results show that PITALRE has a substrate site
      specificity distinguishable from those of the CDC2 and cyclin-dependent kinase 2
      (CDK2).

PMID- 9003390
TI  - Tamoxifen inhibits nitrobenzylthioinosine-sensitive equilibrative uridine
      transport in human MCF-7 breast cancer cells.
AB  - Tamoxifen inhibits the binding of [3H]nitrobenzylthioinosine ([3H]NBMPR) to human
      MCF-7 breast cancer cells with an IC50 of 8 microM. Tamoxifen at 30 microM
      changed the apparent Kd for [3H]NBMPR binding from 0.63 +/- 0.12 to 4.75 +/- 0.58
      nM, with little effect on the Bmax (311000 +/- 76000 and 263000 +/- 46000 sites
      per cell for untreated and tamoxifen-treated cells respectively). Corresponding
      to this decrease in binding of [3H]NBMPR in the presence of tamoxifen was an
      inhibition of NBMPR-sensitive equilibrative transport of 50 microM [3H]uridine
      (IC50 7-10 microM). In the presence of 15 microM tamoxifen, the apparent K(m) for
      [3H]uridine transport was increased from 390 +/- 30 to 1500 +/- 250 microM, with
      no change in Vmax (12.0 +/- 0.1 and 11.3 +/- 4.3 microM/s for untreated and
      tamoxifen-treated cells respectively). The inhibitory effect of tamoxifen on
      NBMPR-sensitive equilibrative uridine transport was specific, as similar results
      were also observed in HL-60 leukaemia and EL4 lymphoma cells. Furthermore a
      similar concentration of tamoxifen had no effect on the NBMPR-insensitive
      equilibrative transport of uridine in MCF-7, HL-60 and Morris 7777 hepatoma
      cells, and on the Na(+)-dependent transport of uridine in murine splenocytes. In
      this paper we demonstrate that tamoxifen by itself might have some
      antiproliferative effects through inhibition of DNA synthesis by blocking the
      nucleoside salvage pathway.

PMID- 9003391
TI  - Increase of particulate nitric oxide synthase activity and peroxynitrite
      synthesis in UVB-irradiated keratinocyte membranes.
AB  - Here we demonstrate that human keratinocytes possess a Ca2+/calmodulin-dependent
      particulate NO synthase that can be activated to release NO after exposure to UVB
      radiation. UVB irradiation (up to 20 mJ/cm2) of human keratinocyte plasma
      membranes resulted in a dose-dependent increase in NO and L-[3H]citrulline
      production that was inhibited by approx. 90% in the presence of N-monomethyl-L
      arginine (L-NMMA). In time-course experiments with UVB-irradiated plasma
      membranes the changes in NO production were followed by analogous changes in
      soluble guanylate cyclase (sGC) activity. In reconstitution experiments, when
      particulate NO synthase was added to purified sGC isolated from keratinocyte
      cytosol, a 4-fold increase in cGMP was observed; the cGMP was increased by NO
      synthesized after UVB irradiation (up to 20 mJ/cm2) of particulate NO synthase. A
      5-fold increase in superoxide (O2-) and a 7-fold increase in NO formation
      followed by an 8-fold increase in peroxynitrite (ONOO-) production by UVB (20
      mJ/cm2)-irradiated keratinocyte microsomes was observed. UVB radiation (20
      mJ/cm2) decreased plasma membrane lipid fluidity as indicated by steady-state
      fluorescence anisotropy. Membrane fluidity changes were prevented by L-NMMA.
      Changes in Arrhenius plots of particulate NO synthase in combination with changes
      in its allosteric properties induced by UVB radiation are consistent with a
      decreased fluidity of the lipid microenvironment of the enzyme. The present
      studies provide important new clues to the role of NO and ONOO- released by UVB
      irradiated human keratinocytes in skin erythema and inflammation.

PMID- 9003393
TI  - Differences in the kinetics of activation of protein kinases and extracellular
      signal-related protein kinase 1 in colony-stimulating factor 1-stimulated and
      lipopolysaccharide-stimulated macrophages.
AB  - To determine the relevance of mitogen-activated protein kinase activity to
      macrophage proliferation, we measured the stimulation of myelin basic protein
      (MBP) kinase and extracellular signal-related protein kinase (ERK) activity in a
      macrophage cell line (BAC1.2F5), bone marrow-derived macrophages (BMM) and
      resident peritoneal macrophages (RPM). By using an 'ingel' MBP kinase assay the
      activities of renaturable MBP kinases were detected, including several with
      molecular masses similar to those of ERK-1 and ERK-2. These represented a minor
      fraction of total activity and were not activated to an appreciable extent by
      colony-stimulating factor 1 (CSF-1). By using a sensitive and specific immune
      complex kinase assay, activation of ERK-1 by CSF-1 and lipopolysaccharide (LPS)
      was demonstrated. Two kinetically distinct pathways of ERK-1 activation by CSF-1
      were resolved, with peak activations occurring at 5 and 15 min. The kinetics and
      degree of activation were similar in BMM, BAC1.2F5 cells and RPM. LPS activated
      ERK-1 with a single peak at 10-15 min, corresponding to the later peak of
      activation by CSF-1. Thus there was no strict correlation between ERK activation
      and macrophage proliferation.

PMID- 9003392
TI  - Thiol regulation of endotoxin-induced release of tumour necrosis factor alpha
      from isolated rat Kupffer cells.
AB  - Proinflammatory cytokines released by hepatic macrophages (Kupffer cells) have a
      central role in the pathogenesis of liver injury and the cardiovascular
      abnormalities of sepsis. Because cytokine release is controlled primarily at the
      level of gene expression, intracellular signalling mechanisms that control the
      transcription of cytokine genes are critical links to organ injury. Oxidant
      stress up-regulates and antioxidants down-regulate the pleiotropic transcription
      factor NF-kappa B, a DNA-binding protein that induces the expression of cytokines
      and vascular adhesion molecules. Thiol-bearing molecules are also important
      inhibitors of NF-kappa B activation, but whether this inhibition represents an
      antioxidant effect is unknown. This study was undertaken to determine whether
      important endogenous and pharmacological thiols modulate the activation of NF
      kappa B and the release of tumour necrosis factor alpha (TNF-alpha) from Kupffer
      cells and to ascertain whether these effects are mediated through glutathione.
      Exposure of rat Kupffer cells to a physiologically relevant concentration of
      lipopolysaccharide (10 ng/ml) activated NF-kappa B within 1 h and induced the
      release of TNF-alpha over 5 h. Cellular glutathione content remained unchanged
      after lipopolysaccharide exposure, but both glutathione monoethyl ester and N
      acetyl-L-cysteine increased cellular glutathione levels, blocked NF-kappa B
      activation and inhibited the release of TNF-alpha. Inhibition of glutathione
      synthesis prevented the NAC-induced increase in Kupffer cell glutathione, yet it
      did not prevent the inhibition of TNF-alpha release by NAC. Thus the inhibition
      of NF-kappa B activation by pharmacological thiols such as NAC might reflect a
      more general role of the intracellular thiol redox status in NF-kappa B
      regulation rather than the antioxidant properties of these agents.

PMID- 9003394
TI  - Progesterone and the zona pellucida activate different transducing pathways in
      the sequence of events leading to diacylglycerol generation during mouse sperm
      acrosomal exocytosis.
AB  - We tested the involvement of protein tyrosine kinase and G-protein transducing
      pathways in the formation of diacylglycerol (DAG) during exocytosis in mouse
      spermatozoa. In capacitated spermatozoa, stimulation with solubilized zona
      pellucida (ZP) or progesterone led to the formation of DAG and to exocytosis of
      the acrosomal granule. Stimulation of DAG formation and exocytosis by ZP were
      inhibited in a concentration-dependent fashion by pre-exposure to tyrphostin A48,
      a protein tyrosine kinase inhibitor. These ZP-induced responses were also reduced
      in a concentration-dependent manner by prior incubation with pertussis toxin, a G
      protein (Gi class) inhibitor. On the other hand, generation of DAG and exocytosis
      triggered by progesterone were inhibited if spermatozoa were preincubated with
      different concentrations of tyrphostin A48, but were not affected by pre-exposure
      to pertussis toxin. Progesterone acts on at least two novel surface receptors,
      one being a gamma-aminobutyric acid (GABA) type A (GABAA)-like receptor.
      Transducing mechanisms coupled to this receptor were tested directly by
      stimulating spermatozoa with GABA. Treatment of capacitated spermatozoa with GABA
      resulted in DAG formation and exocytosis. These responses were not seen when
      cells were preincubated with tyrphostin A48. Pertussis toxin, however, did not
      affect the generation of DAG and exocytosis triggered by GABA, in agreement with
      results obtained using progesterone. Taken together, these results indicate that
      DAG formation during acrosomal exocytosis is differentially regulated by
      transducing pathways activated by oocyte-associated agonists.

PMID- 9003396
TI  - Arterial oxygen partial pressures reduce the insulin-dependent induction of the
      perivenously located glucokinase in rat hepatocyte cultures: mimicry of arterial
      oxygen pressures by H2O2.
AB  - Liver glucokinase (GK) is localized predominantly in the perivenous zone. GK mRNA
      was induced by insulin maximally under venous O2 partial pressure (pO2) and only
      half-maximally under arterial pO2. CoCl2 and desferrioxamine mimicked venous pO2
      and enhanced the insulin-dependent induction of GK mRNA under arterial pO2. H2O2
      mimicked arterial pO2 and reduced insulin-induced GK mRNA under venous pO2 to the
      lower arterial levels. Thus the zonal O2 gradient in liver seems to have a key
      role in the heterogenous expression of the GK gene.

PMID- 9003395
TI  - Adipocyte differentiation-related protein is secreted into milk as a constituent
      of milk lipid globule membrane.
AB  - Milk lipid globules from humans, cows and rats contained a protein identified as
      adipocyte differentiation-related protein (ADRP) associated with the globule
      surface membrane material. This protein, previously believed to be specific to
      adipocytes, was a major constituent of the globule surface and was present in a
      detergent-insoluble complex that contained stoichiometric amounts of butyrophilin
      and xanthine oxidase. Identification of ADRP was by sequence similarity of
      tryptic peptides from cow and human proteins with the sequence inferred from the
      cDNA for mouse ADRP. The putative ADRP of lipid globules from cow, human and rat
      milk was recognized specifically by antisera raised against a peptide synthesized
      to duplicate the N-terminal 26 residues of the mouse protein. In homogenates of
      lactating mammary gland, ADRP was found only in endoplasmic reticulum and in
      lipid droplet fractions. ADRP was modified, apparently post-translationally, and
      one modification apparently was acylation, primarily with C14, C16 and C18 fatty
      acids. Two isoelectric variants of ADRP were present in cow globule membrane
      material. In vitro, ADRP served as a substrate for protein kinases associated
      with milk lipid globule membrane, but this protein did not seem to become
      phosphorylated intracellularly.

PMID- 9003397
TI  - Peroxisomal multifunctional enzyme of beta-oxidation metabolizing D-3-hydroxyacyl
      CoA esters in rat liver: molecular cloning, expression and characterization.
AB  - In the present study we have cloned and characterized a novel rat peroxisomal
      multifunctional enzyme (MFE) named perMFE-II. The purified 2-enoyl-CoA hydratase
      2 with an M(r) of 31500 from rat liver [Malila, Siivari, Makela, Jalonen,
      Latipaa, Kunau and Hiltunen (1993) J. Biol. Chem. 268, 21578-21585] was subjected
      to tryptic fragmentation and the resulting peptides were isolated and sequenced.
      Surprisingly, the full-length cDNA, amplified by PCR, had an open reading frame
      of 2205 bp encoding a polypeptide with a predicted M(r) of 79,331 and contained a
      potential peroxisomal targeting signal in the C-terminus (Ala-Lys-Leu). The
      sequenced peptide fragments of hydratase 2 gave a full match in the middle
      portion of the cDNA-derived amino acid sequence. The predicted amino acid
      sequence showed a high degree of similarity with pig 17 beta-hydroxysteroid
      dehydrogenase type IV and MFE of yeast peroxisomal beta-oxidation. Recombinant
      perMFE-II (produced in Pichia pastoris) had 2-enoyl-CoA hydratase 2 and D
      specific 3-hydroxyacyl-CoA dehydrogenase activities and was catalytically active
      with several straight-chain trans-2-enoyl-CoA, 2-methyltetradecenoyl-CoA and
      pristenoyl-CoA esters. The results showed that in addition to an earlier
      described multifunctional isomerase-hydratase-dehydrogenase enzyme from rat liver
      peroxisomes (perMFE-I), another MFE exists in rat liver peroxisomes. They both
      catalyse sequential hydratase and dehydrogenase reactions of beta-oxidation but
      through reciprocal stereochemical courses.

PMID- 9003398
TI  - Roles of the signal peptide and mature domains in the secretion and maturation of
      the neutral metalloprotease from Streptomyces cacaoi.
AB  - The neutral metalloprotease (Npr) of Streptomyces cacaoi is synthesized as a
      prepro-Npr precursor form consisting of a secretory signal peptide, a propeptide
      and the mature metalloprotease. The maturation of Npr occurs extracellularly via
      an autoproteolytic processing of the secreted pro-Npr. The integrity of the
      propeptide is essential for the formation of mature active Npr but not for its
      secretion [Chang, Chang and Lee (1994) J. Biol. Chem. 269, 3548-3554]. In this
      study we investigated whether the secretion and maturation of Npr require the
      integrity of its signal peptide region and mature protease domain. Five signal
      peptide mutants were generated, including the substitution mutations at the
      positively charged region (mutant IR6LE), the central hydrophobic region (mutants
      GI19EL and G19N), the boundary of the hydrophobic core-cleavage region (mutant
      P30L) and at the residues adjacent to the signal peptidase cleavage site (mutant
      YA33SM). All these lesions delayed the export of Npr to the growth medium and
      also resulted in a 2-10-fold decrease in Npr export. The most severe effect was
      noted in mutants GI19EL and P30L. When these signal peptide mutations were fused
      separately with the propeptide lacking the Npr mature domain, the secretory
      defect on the propeptide was also observed, and this impairment was again more
      severely expressed in mutants GI19EL and P30L. Thus the Npr signal peptide seems
      to have more constraints on the hydrophobic core region and at the proline
      residue within the boundary of the hydrophobic core-cleavage site. Deletion
      mutations within the C-terminal mature protease domain that left its active site
      intact still blocked the proteolytic processing of mutant precursor forms of pro
      Npr, although their secretions were unaffected. These results, together with our
      previous findings, strongly suggest that the signal peptide of Npr plays a
      pivotal role in the secretion of both Npr and the propeptide, but not in the
      maturation of Npr. On the contrary, the integrity of mature domain and propeptide
      is not critical for secretion of the Npr derivative but is essential for the
      formation of a functional Npr. Therefore the secretion and maturation of Npr are
      dependent on the integrity of the signal peptide, propeptide and mature protease
      domains, and the roles of these domains in this regard are functionally distinct.

PMID- 9003399
TI  - Effect of genotype on the levels of surfactant protein A mRNA and on the SP-A2
      splice variants in adult humans.
AB  - Human pulmonary surfactant protein A (SP-A) is encoded by two genes, SP-A1 and SP
      A2, that exhibit coding sequence (allelic) and 5' splicing variability. In this
      report we determine the effect of the genetic variability within the SP-A1 and SP
      A2 genes on the level of SP-A mRNAs and on the SP-A2 splicing variants in
      different individuals. We analysed mRNA specimens from 23 unrelated adults using
      genotype analysis, Northern analysis and primer extension, and made the following
      observations. (1) The level of SP-A mRNA varies among individuals (coefficient of
      variation = 0.49). One SP-A genotype (6A(2)6A(2)1A(0)1A0) appears to be
      associated with a low to moderate level of SP-A mRNA. (2) The SP-A1/SP-A2 mRNA
      ratio varies among individuals, from 0.94 (lowest) to 6.80 (highest) within the
      study population. One genotype appears to be associated with a moderate to high
      SP-A1/SP-A2 mRNA ratio and another with a low to moderate ratio. (3) There is no
      correlation between the level of SP-A mRNA and the SP-A1/SP-A2 mRNA ratio. (4)
      Variability in the ratio of the major SP-A2 splice variants among individuals
      results from nucleotide differences in the splice-recognition sequence of
      specific SP-A2 alleles. The SP-A mRNA levels, the SP-A1/SP-A2 mRNA ratio, and the
      ratio of the major SP-A2 splice variants have a genetic basis in that they vary
      depending upon the specific SP-A alleles present.

PMID- 9003400
TI  - The transmembrane domain of diphtheria toxin improves molecular conjugate gene
      transfer.
AB  - Vectors based on the formation of a soluble DNA-polycation complex are being
      developed for the treatment of human diseases. These complexes are rapidly taken
      up by receptor-mediated endocytosis, but are inefficiently delivered to the
      nucleus owing to entrapment in membrane-bound vesicles. In this study we
      introduced the transmembrane domain of diphtheria toxin into a DNA-polycation
      conjugate complex in an effort to increase gene transfer by membrane
      perturbation. The transmembrane domain of diphtheria toxin was expressed in
      Escherichia coli as a maltose-binding protein fusion and chemically coupled to
      high-molecular-mass poly-L-lysine. Incorporation of this conjugate into a
      traditional complex formed with a luciferase-containing plasmid with an asialo
      orosomucoid-polycation conjugate significantly increased transfection efficiency
      in vitro in a manner proportional to the amount of diphtheria toxin incorporated.
      The delivery of luciferase RNA transcript was similarly increased when complexed
      with similar polycation conjugates. This study uses the structural biology of a
      bacterial protein to improve polycation-based gene delivery.

PMID- 9003401
TI  - EF-hand motifs of alpha, beta and gamma isoforms of diacylglycerol kinase bind
      calcium with different affinities and conformational changes.
AB  - The three diacylglycerol kinase isoenzymes (DGK alpha, DGK beta and DGK gamma)
      cloned so far contain in common a tandem repeat of EF-hand motifs. However, the
      Ca2+ dependences of the DGK activities are known to be variable between
      isoenzymes, and the Ca(2+)-binding activities of these motifs have not been
      tested except for those present in DGK alpha. We therefore attempted to define
      the intrinsic properties of EF-hands occurring in the DGK isoenzymes. For this
      purpose we bacterially expressed and purified the EF-hand motifs (termed DKE
      forms) of the three DGKs. Equilibrium dialysis with the purified DKE forms showed
      that all of the expressed proteins could bind approx. 2 mol of Ca2+ per mol.
      However, the apparent dissociation constant (Kd) for calcium binding to alpha-DKE
      (9.9 microM) was an order of magnitude greater than those estimated for beta-DKE
      (0.89 microM) and gamma-DKE (0.40 microM). Experiments with 2-p-toluidinyl
      naphthalene 6-sulphonate, a probe for hydrophobic regions of proteins, showed
      that the binding of Ca2+ to beta-DKE resulted in the exposure of hydrophobic
      amino acids, whereas hydrophobic regions of alpha-DKE and gamma-DKE were masked
      by the addition of Ca2+. Taken together, these results indicate that DGK alpha,
      DGK beta and DGK gamma possess EF-hand structures with intrinsic properties
      different from each other with respect to affinities for Ca2+ and Ca(2+)-induced
      conformational changes.

PMID- 9003402
TI  - pH-dependent processing of secretogranin II by the endopeptidase PC2 in isolated
      immature secretory granules.
AB  - We have previously characterized the processing of secretogranin II (SgII) in
      PC12 cells that were stably transfected with the endopeptidase PC2. Here we show
      that processing of SgII can be observed in isolated immature secretory granules
      (ISGs) derived from this cell line in a temperature- and ATP-dependent manner.
      The stimulatory effect of ATP on processing can be attributed to the activation
      of the vacuolar H(+)-ATPase and a concomitant decrease in intragranular pH. The
      immature secretory granule therefore provides an adequate environment for correct
      processing of SgII by PC2. The rate of SgII processing was strongly dependent on
      the intragranular pH, suggesting that processing of SgII can be used as a pH
      indicator for the granule interior. A standard curve was prepared using SgII
      processing in ISGs equilibrated at a range of pH values. The extent of processing
      in ISGs incubated in the presence of ATP at physiological pH was compared with
      the standard curve, and the intragranular pH was determined. From these
      observations, we propose an intragranular pH of 6.3 +/- 0.1 for ISGs in a
      physiological buffer in the presence of ATP. Hence, the pH of ISGs seems to be
      similar to the pH of the trans-Golgi network (TGN) and is clearly higher than the
      pH of mature secretory granules (pH 5.0-5.5). Interestingly, no processing of
      SgII could be observed in a membrane fraction that is highly enriched in TGN
      under conditions for which processing was readily obtained in isolated ISGs.

PMID- 9003403
TI  - Regulation of cell surface GLUT4 in skeletal muscle of transgenic mice.
AB  - Marked overexpression of the glucose transporter GLUT4 in skeletal muscle
      membrane fractions of GLUT4 transgenic (TG) mice is accompanied by
      disproportionately small increases in basal and insulin-stimulated glucose
      transport activity. Thus we have assessed cell surface GLUT4 by photolabelling
      with the membrane-impermeant reagent 2-N-[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]
      1, 3-bis(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA) and measured the
      corresponding glucose transport activity using 2-deoxyglucose in isolated
      extensor digitorum longus (EDL) muscles from non-transgenic (NTG) and GLUT4 TG
      mice in the absence and presence of 13.3 nM (2000 mu units/ml) insulin, without
      or with hypoxia as a model of muscle contraction. TG mice displayed elevated
      rates of glucose transport activity under basal and insulin-stimulated
      conditions, and in the presence of insulin plus hypoxia, compared with NTG mice.
      Photoaffinity labelling of cell surface GLUT4 indicated corresponding elevations
      in plasma membrane GLUT4 in the basal and insulin-stimulated states, and with
      insulin plus hypoxia, but no difference in cell surface GLUT4 during hypoxia
      stimulation. Subcellular fractionation of hindlimb muscles confirmed the
      previously observed 3-fold overexpression of GLUT4 in the TG compared with the
      NTG mice. These results suggest that: (1) alterations in glucose transport
      activity which occur with GLUT4 overexpression in EDL muscles are directly
      related to cell surface GLUT4 content, regardless of the levels observed in the
      corresponding subcellular membrane fractions, (2) while overexpression of GLUT4
      influences both basal and insulin-stimulated glucose transport activity, the
      response to hypoxia/ contraction-stimulated glucose transport is unchanged, and
      (3) subcellular fractionation provides little insight into the subcellular
      trafficking of GLUT4, and whatever relationship is demonstrated in EDL muscles
      from NTG mice is disrupted on GLUT4 overexpression.

PMID- 9003404
TI  - Protease digestion studies of an equilibrium intermediate in the unfolding of
      creatine kinase.
AB  - Protease digestion experiments have been used to characterize the structure of an
      equilibrium intermediate in the unfolding of creatine kinase (CK) by low
      concentrations (0.625 M) of guanidine hydrochloride (GdnHCl). Eighteen of the
      major products of digestion by trypsin, chymotrypsin and endoproteinase Glu-C
      have been identified by microsequencing after separation by SDS/PAGE and
      electroblotting on poly(vinylidene difluoride) membranes. The C-terminal portion
      (Gly215 to Lys380) was much more resistant to digestion than the N-terminal
      portion (Pro1 to Gly133), although the area most sensitive to proteolysis was in
      the middle of the CK sequence (Arg134 to Arg214). These experiments are
      consistent with the two-domain model for the CK monomer. The structure of the
      intermediate is proposed to consist of a folded C-terminal domain and a partly
      folded N-terminal domain separated by an unfolded central linker. Protease
      susceptibility is clustered within two N-terminal regions and one central region.
      These regions are evidently exposed as a result of the partial unfolding and/or
      separation of the N-terminal domain. Further evidence for the structure of this
      intermediate comes from gel filtration studies. Treatment of CK with 0.625 M
      GdnHCl resulted in slow aggregation at 37 degrees C, but not at 12 degrees C, a
      phenomenon previously reported for phosphoglycerate kinase. The aggregation did
      not occur at higher GdnHCl concentrations and was unaffected by a reducing agent.
      It is proposed that aggregation is a consequence of non-specific interactions
      between hydrophobic regions, possibly domain/domain interfaces, which become
      exposed in the intermediate.

PMID- 9003405
TI  - Rab 3D in rat adipose cells and its overexpression in genetic obesity (Zucker
      fatty rat).
AB  - Members of the Rab 3 subfamily of low-molecular-mass GTP-binding proteins have
      been functionally implicated in regulated exocytosis. The aim of the present
      study was to examine the subcellular distribution of a member of this family, Rab
      3D, in rat adipose cells, given the hypothesis that this protein might be
      involved in insulin-stimulated GLUT4 exocytosis. We show that Rab 3D
      immunoreactivity is associated predominantly with the high-density microsomal
      fraction, where the signal intensity is 3- and 7-fold greater than that in plasma
      membranes and low-density microsomes respectively. Rab 3D does not co-localize
      with GLUT4 on immuno-isolated intracellular vesicles and, unlike GLUT4, it is not
      redistributed in response to insulin. Thus, if Rab 3D plays a role in GLUT4
      trafficking, it relies on mechanisms independent of relocation. We observed that
      Rab 3D is overexpressed in adipose cells of obese (fa/fa) Zucker rats, in a
      tissue- and isoform-specific manner. The pathophysiological significance of this
      defect remains elusive. This could form the molecular basis for altered adipose
      secretory function in obesity.

PMID- 9003406
TI  - Evidence for a negative Pasteur effect in articular cartilage.
AB  - Uptake of external glucose and production of lactate were measured in freshly
      excised bovine articular cartilage under O2 concentrations ranging from 21% (air)
      to zero (N2-bubbled). Anoxia (O2 concentration < 1% in the gas phase) severely
      inhibited both glucose uptake and lactate production. The decrease in lactate
      formation correlated closely with the decrease in glucose uptake, in a mole ratio
      of 2:1. This reduction in the rate of glycolysis in anoxic conditions is seen as
      evidence of a negative Pasteur effect in bovine articular cartilage. Anoxia also
      suppressed glycolysis in articular cartilage from horse, pig and sheep.
      Inhibitors acting on the glycolytic pathway (2-deoxy-D-glucose, iodoacetamide or
      fluoride) strongly decreased aerobic lactate production and ATP concentration,
      consistent with the belief that articular cartilage obtains its principal supply
      of ATP from substrate-level phosphorylation in glycolysis. Azide or cyanide
      lowered the ATP concentration in aerobic cartilage to approximately the same
      extent as did anoxia but, because glycolysis (lactate production) was also
      inhibited by these treatments, the importance of any mitochondrial ATP production
      could not be assessed. A negative Pasteur effect would make chondrocytes
      particularly liable to suffer a shortage of energy under anoxic conditions.
      Incorporation of [35S]sulphate into proteoglycan was severely curtailed by
      treatments, such as anoxia, which decreased the intracellular concentration of
      ATP.

PMID- 9003407
TI  - Interleukin 6 activates heat-shock protein 90 beta gene expression.
AB  - The levels of the cytokine interleukin-6 (IL-6) and the heat-shock protein hsp90
      have both been reported to be elevated in patients with active systemic lupus
      erythematosus (SLE). We show that hsp90 protein accumulates to increased levels
      in both HuH7 hepatoma cells and peripheral blood mononuclear cells (PBMCs)
      treated with IL-6. In PBMCs this effect occurs without induction of the other
      hsps, paralleling the specific elevation of hsp90 in SLE. IL-6 is able to
      activate the hsp90 gene promoter directly; this activation can also be achieved
      by overexpressing either of the transcription factors NF-IL-6 or NF-IL-6 beta
      whose synthesis is induced by IL-6 treatment. Hence the induction of hsp90
      protein accumulation by IL-6 is likely to be dependent on the enhanced activity
      of the hsp90 beta gene promoter produced by increased levels of NF-IL-6 and/or NF
      IL-6 beta. These effects are discussed in terms of the role of hsp90 in the
      normal immune system and the mechanism of its activation in patients with SLE.

PMID- 9003408
TI  - Characterization of novel calmodulin-binding peptides with distinct inhibitory
      effects on calmodulin-dependent enzymes.
AB  - We describe the isolation and interaction with calmodulin (CaM) of two 10-amino
      acid peptides (termed peptides 1 and 2; AWDTVRISFG and AWPSLQAIRG respectively)
      derived from a phage random peptide display library. Both peptides are shorter
      than previously described CaM-binding peptides and lack certain features found in
      the sequences of CaM-binding domains present in CaM-activated enzymes. However,
      1H NMR spectroscopy and fluorimetry indicate that both peptides interact with CaM
      in the presence of Ca2+. The two peptides differentially inhibited CaM-dependent
      kinases I and II (CaM kinases I and II) but did not affect CaM-dependent
      phosphodiesterase. Peptide 1 inhibited CaM kinase I but not CaM kinase II,
      whereas peptide 2 inhibited CaM kinase II, but only partially inhibited CaM
      kinase I at a more than 10-fold higher concentration. Peptide 1 also inhibited a
      plant calcium-dependent protein kinase, whereas peptide 2 did not. The ability of
      peptides 1 and 2 to differentially inhibit CaM-dependent kinases and CaM
      dependent phosphodiesterase suggests that they may bind to distinct regions of
      CaM that are specifically responsible for activation of different CaM-dependent
      enzymes.

PMID- 9003409
TI  - Mucus glycoproteins in bovine trachea: identification of the major mucin
      populations in respiratory secretions and investigation of their tissue origins.
AB  - Bovine respiratory secretions were separated into gel and sol phases to allow the
      identification of the gel-forming mucins. Mucins were subsequently isolated from
      the surface epithelium and submucosal tissue to investigate the tissue origins of
      the species in the secretions. Density-gradient centrifugation revealed 'high
      density' and 'low-density' mucins in the gel phase of the secretions. The 'high
      density' mucins were large, composed of subunits joined by disulphide bonds and
      contained two highly glycosylated domains of apparently different lengths,
      whereas the 'low-density' mucins were smaller and monomeric. The sol also
      contained both 'high-density' and 'low-density' species. A 'high-density' mucin
      similar to that in the gel was isolated from the surface epithelium, suggesting
      that the goblet cells produce large, gel-forming mucins. A second 'high-density'
      species was released from the submucosal tissue after reduction/alkylation,
      indicating that large mucins from the submucosal glands may also be a component
      of the mucus gel. In addition, two small, 'low-density' mucins were obtained from
      the submucosal tissue. One species was associated with the gel phase but was also
      present in the sol, whereas the other was present only in the sol. Bovine
      respiratory-tract secretions thus comprise a complex mixture of large gel-forming
      mucins originating from the goblet cells and submucosal glands, and smaller
      'soluble' species from the submucosal glands which may interact with the gel.

PMID- 9003411
TI  - Metabolic control analysis of biochemical pathways based on a thermokinetic
      description of reaction rates.
AB  - Metabolic control analysis is a powerful technique for the evaluation of flux
      control within biochemical pathways. Its foundation is the elasticity
      coefficients and the flux control coefficients (FCCs). On the basis of a
      thermokinetic description of reaction rates it is here shown that the elasticity
      coefficients can be calculated directly from the pool levels of metabolites at
      steady state. The only requirement is that one thermodynamic parameter be known,
      namely the reaction affinity at the intercept of the tangent in the inflection
      point of the curve of reaction rate against reaction affinity. This parameter can
      often be determined from experiments in vitro. The methodology is applicable only
      to the analysis of simple two-step pathways, but in many cases larger pathways
      can be lumped into two overall conversions. In cases where this cannot be done it
      is necessary to apply an extension of the thermokinetic description of reaction
      rates to include the influence of effectors. Here the reaction rate is written as
      a linear function of the logarithm of the metabolite concentrations. With this
      type of rate function it is shown that the approach of Delgado and Liao [Biochem.
      J. (1992) 282, 919-927] can be much more widely applied, although it was
      originally based on linearized kinetics. The methodology of determining
      elasticity coefficients directly from pool levels is illustrated with an analysis
      of the first two steps of the biosynthetic pathway of penicillin. The results
      compare well with previous findings based on a kinetic analysis.

PMID- 9003410
TI  - The human EBNA-2 coactivator p100: multidomain organization and relationship to
      the staphylococcal nuclease fold and to the tudor protein involved in Drosophila
      melanogaster development.
AB  - The human p100 protein was recently identified as a coactivator of the Epstein
      Barr virus nuclear antigen 2. On the basis of sequence analysis with the
      hydrophobic cluster analysis method, we predict that this protein consists of a
      repeat of four similar domains. Their fold can be related to the staphylococcal
      nuclease structure whose first subdomain belongs to the large
      oligonucleotide/oligosaccharide-binding (OB)-fold superfamily. The catalytic
      amino acids present in nucleases are missing, however, suggesting that these
      repeated motifs could only serve to bind DNA without catalytic activity, as in
      many other OB-folds. A highly modified fifth domain follows the four nuclease
      like domains, conserving the second subdomain of the nuclease structure but not
      the first one (the OB-fold), which is replaced by an original domain found in
      multiple copies in the tudor protein, a Drosophila melanogaster protein required
      during oogenesis for establishment of a functional posterior organizing centre.
      We named this heretofore undescribed domain the 'tudor domain' and highlight
      within it five invariant residues which could be involved in one of the essential
      roles played by these proteins.

PMID- 9003412
TI  - Interaction between ATP, oleandomycin and the OleB ATP-binding cassette
      transporter of Streptomyces antibioticus involved in oleandomycin secretion.
AB  - The OleB protein of Streptomyces antibioticus, oleandomycin (OM) producer,
      constitutes an ATP-binding cassette transporter containing two nucleotide-binding
      domains and is involved in OM resistance and its secretion in this producer
      strain. We have characterized some properties of the first nucleotide-binding
      domain of OleB using an overexpressed fusion protein (MBP-OleB') between a
      maltose-binding protein (MBP) and the first half of OleB (OleB'). Extrinsic
      fluorescence of the base-modified fluorescent nucleotide analogue 1,N6
      ethenoadenosine 5'-triphosphate (epsilon ATP) and 2'(3')-o-(2,4,6
      trinitrophenyl)adenosine-5'-triphosphate was determined in the presence of MBP
      and the fusion protein MBP-OleB', and it was found that epsilon ATP binds to MBP
      OleB' with a stoichiometry of 0.9. Measurements of the intrinsic fluorescence of
      the MBP-OleB' fusion protein indicated that ATP induces a decrease in the
      accessibility of the MBP-OleB' tryptophans to acrylamide, an indication of a
      folding effect. This conclusion was confirmed by the fact that ATP also induces
      considerable stabilization against guanidine chloride denaturation of MBP-OleB'.
      Two effects were found to be associated with the presence of Mg2+ ions: (1) an
      increase in the quenching of MBP-OleB' intrinsic fluorescence by ATP; and (2) an
      increase in the accessibility of MBP-OleB' tryptophans to acrylamide. Significant
      changes in the intrinsic fluorescence of the fusion protein were also observed in
      the presence of OM, demonstrating the existence of interaction between the
      transporter and the antibiotic in the absence of any hydrophobic membrane
      component.

PMID- 9003413
TI  - Marked increases in concentrations of apolipoprotein in the cerebrospinal fluid
      of poliovirus-infected macaques: relations between apolipoprotein concentrations
      and severity of brain injury.
AB  - Apolipoproteins in cerebrospinal fluid (CSF) might have important functional
      roles in the pathophysiology of brain and lipid metabolism in the vascular
      component. The present study examined apolipoprotein A-I (apo-A-I) and
      apolipoprotein E (apo-E) levels in CSF and serum from poliovirus-infected
      macaques. Poliovirus-infected macaques developed motor deficits and were
      classified into three groups: (1) muscle weakness in one or both legs; (2)
      partial paralysis in one or both legs; (3) complete paralysis in one or both
      legs. No motor deficits were evident in the control or sham-treated macaques. Apo
      A-I concentrations in CSF were markedly elevated in poliovirus-infected macaques
      with weakness, partial or complete paralysis, in comparison with either control
      or sham-treated animals, and were proportional to the severity of motor
      impairment. Apo-E concentrations in CSF were also significantly elevated in
      poliovirus-infected macaques with complete paralysis. The magnitude of increase
      in CSF apo-A-I or apo-E concentrations was also closely associated with the
      degree of histologic neurological damage and inflammation (lesion scores).
      However, no changes in serum apo-A-I and apo-E concentrations were observed in
      the poliovirus-infected macaques compared with control macaques. Furthermore
      there were no significant correlations apo-A-I or apo-E concentrations between
      serum and CSF. We hypothesize that the elevation of apo-A-I and apo-E
      concentrations after poliovirus infection is caused by immune stimulation within
      the central nervous system (CNS). Measures of CSF apo-A-I and apo-E levels might
      serve as a useful marker for the severity and/or the range of CNS injury.

PMID- 9003414
TI  - Novel isoform of syntaxin 1 is expressed in mammalian cells.
AB  - Syntaxin 1A has been identified previously as a neural-cell-specific, membrane
      anchored receptor protein required for docking and fusion of synaptic vesicles
      with the presynaptic plasma membrane. Syntaxin 1A consists of 288 amino acid
      residues including a 265-residue N-terminal region exposed to the cytoplasm and a
      C-terminal hydrophobic stretch of 23 residues believed to anchor syntaxin to the
      plasma membrane. Using a human fat-cell library we have isolated a novel cDNA
      clone of syntaxin 1A containing an insert of 91 bp in codon 226. This insert and
      subsequent frame shift generated a cDNA that codes for a truncated protein of 260
      residues without the C-terminal transmembrane domain characteristic of the
      syntaxin family. Analysis of the deduced amino acid sequence of the new cDNA
      clone, termed syntaxin 1C, showed that it was identical for the first 226
      residues with the previously described neural syntaxin 1A, and diverged
      thereafter. The truncated protein lacked the botulinum neurotoxin C cleavage site
      (Lys253-Ala254), a feature of the syntaxin 1A protein, because of the novel C
      terminal domain of 34 residues. The new C-terminal region contained a single
      cysteine residue and was moderately rich in proline, with three repeats of a PXP
      motif. The insert occurred within the region encoding the coiled-coil motifs
      required for interactions with synaptobrevin, alpha-SNAP (SNAP being soluble N
      ethylmaleimide-sensitive factor attachment protein) and n-Sec1/Munc-18 (n-Sec1
      being the rat brain homologue of yeast Sec1p and Munc-18 the mammalian homologue
      of Caenorhabditis elegans unc-18, but five residues outside the domain previously
      mapped as being required for binding SNAP-25. Interaction studies in vitro
      suggested that unlike syntaxin 1A, which binds to both Munc-18a and- 18b,
      syntaxin 1C binds only to Munc-18b. The new isoform syntaxin 1C, which might be
      generated by alternative splicing of the syntaxin 1 gene, was expressed in
      several human tissues, including brain. Immuno-precipitation and immunoblotting
      with the monoclonal antibody HPC-1 and a polyclonal antibody raised against a
      peptide corresponding to the unique C-terminal 35 residues of syntaxin 1C failed
      to detect syntaxin 1C at the protein level in extracts of muscle, fat or brain.

PMID- 9003415
TI  - Receptor-mediated stimulation of lipid signalling pathways in CHO cells elicits
      the rapid transient induction of the PDE1B isoform of Ca2+/calmodulin-stimulated
      cAMP phosphodiesterase.
AB  - Chinese hamster ovary cells (CHO cells) do not exhibit any Ca2+/calmodulin
      stimulated cAMP phosphodiesterase (PDE1) activity. Challenge of CHO cells with
      agonists for endogenous P2-purinoceptors, lysophosphatidic acid receptors and
      thrombin receptors caused a similar rapid transient induction of PDE1 activity in
      each instance. This was also evident on noradrenaline challenge of a cloned CHO
      cell line transfected so as to overexpress alpha 1B-adrenoceptors. This novel
      PDE1 activity appeared within about 15 min of exposure to ligands, rose to a
      maximum value within 30 min to 1 h and then rapidly decreased. In each case, the
      expression of novel PDE1 activity was blocked by the transcriptional inhibitor
      actinomycin D. Challenge with insulin of either native CHO cells or a CHO cell
      line transfected so as to overexpress the human insulin receptor failed to induce
      PDE1 activity. Reverse transcriptase-PCR analyses, using degenerate primers able
      to detect the PDE1C isoform, did not amplify any fragment from RNA preparations
      of CHO cells expressing PDE1 activity, although they did so from the human
      thyroid carcinoma FTC133 cell line. Reverse transcriptase-PCR analyses, using
      degenerate primers able to detect the PDE1A and PDE1B isoforms, successfully
      amplified a fragment of the predicted size from RNA preparations of both CHO
      cells expressing PDE1 activity and human Jurkat T-cells. Sequencing of the PCR
      products, generated using the PDE1A/B primers, yielded a novel sequence which, by
      analogy with sequences reported for bovine and murine PDE1B forms, suggests that
      the PDE1 species induced in CHO cells through protein kinase C activation and
      that expressed in Jurkat T-cells are PDE1B forms.

PMID- 9003416
TI  - Challenge of human Jurkat T-cells with the adenylate cyclase activator forskolin
      elicits major changes in cAMP phosphodiesterase (PDE) expression by up-regulating
      PDE3 and inducing PDE4D1 and PDE4D2 splice variants as well as down-regulating a
      novel PDE4A splice variant.
AB  - The cAMP phosphodiesterase (PDE) 3 and PDE4 isoforms provide the major cAMP
      hydrolysing PDE activities in Jurkat T-cells, with additional contributions from
      the PDE1 and PDE2 isoforms. Challenge of cells with the adenylate cyclase
      activator forskolin led to a rapid, albeit transient, increase in PDE3 activity
      occurring over the first 45 min, followed by a sustained increase in PDE3
      activity which began after approximately 3 h and continued for at least 24 h.
      Only this second phase of increase in PDE3 activity was blocked by the
      transcriptional inhibitor actinomycin D. After approximately 3 h of exposure to
      forskolin, PDE4 activity had increased, via a process that could be inhibited by
      actinomycin D, and it remained elevated for at least a 24 h period. Such actions
      of forskolin were mimicked by cholera toxin and 8-bromo-cAMP. Forskolin increased
      intracellular cAMP concentrations in a time-dependent fashion and its action was
      enhanced when PDE induction was blocked with actinomycin D. Reverse transcription
      (RT)-PCR analysis, using generic primers designed to detect transcripts
      representing enzymically active products of the four PDE4 genes, identified
      transcripts for PDE4A and PDE4D but not for PDE4B or PDE4C in untreated Jurkat T
      cells. Forskolin treatment did not induce transcripts for either PDE4B or PDE4C;
      however, it reduced the RT-PCR signal for PDE4A transcripts and markedly enhanced
      that for PDE4D transcripts. Using RT-PCR primers for PDE4 splice variants, a weak
      signal for PDE4D1 was evident in control cells whereas, in forskolin-treated
      cells, clear signals for both PDE4D1 and PDE4D2 were detected. RT-PCR analysis of
      the PDE4A species indicated that it was not the PDE4A isoform PDE-46 (PDE4A4B).
      Immunoblotting of control cells for PDE4 forms identified a single PDE4A species
      of approximately 118 kDa, which migrated distinctly from the PDE4A4B isoform PDE
      46, with immunoprecipitation analyses showing that it provided all of the PDE4
      activity in control cells. Forskolin treatment led to a marked decrease of this
      novel PDE4A species and allowed the detection of a strong signal for an
      approximately 67 kDa PDE4D species, suggested to be PDE4D1, but did not induce
      PDE4B and PDE4C isoforms. Elevation of intracellular cAMP concentrations in
      Jurkat T-cells thus exerts a highly selective effect on the transcriptional
      activity of the genes encoding the various PDE4 isoforms. This leads to the down
      regulation of a novel PDE4A splice variant and the induction of PDE4D1 and PDE4D2
      splice variants, leading to a net increase in the total PDE4 activity of Jurkat T
      cells.

PMID- 9003417
TI  - Intracellular localization of the PDE4A cAMP-specific phosphodiesterase splice
      variant RD1 (RNPDE4A1A) in stably transfected human thyroid carcinoma FTC cell
      lines.
AB  - Cells of two human follicular thyroid carcinoma cell lines (FTC133, FTC236) were
      stably transfected with a cDNA encoding the PDE4A cAMP-specific phosphodiesterase
      (PDE) splice variant RD1 (RNPDE4A1A) so as to generate the cloned cell lines,
      FTC133A and FTC236A. This allowed the expression of a novel rolipram-inhibited
      cAMP-specific PDE activity in these cells. Unlike the parent cell lines in which
      Ca2+/calmodulin caused a profound activation (approx. 3-4-fold) of homogenate PDE
      activity, no such stimulation was evident in the RD1-expressing cell lines,
      indicating loss of PDE1 activity. Reverse transcriptase-PCR analysis indicated
      that this was due to the down-regulation of the PDE1C isoform. The novel PDE4
      activity in transfected cells was located exclusively in the membrane fraction,
      as was immunoreactive RD1. Low concentrations of the detergent Triton X-100, but
      not high NaCl concentrations, allowed RD1 to be solubilized. Laser scanning
      confocal immunofluorescence analyses identified RD1 immunoreactivity in a
      discrete perinuclear region of these RD1-expressing transfected cell lines. A
      similar pattern of labelling was observed using the antiserum Tex1, which
      specifically identified the Golgi apparatus. Treatment of FTC133A cells with the
      Golgi-perturbing agents monensin and brefeldin A led to a similar redistribution
      of immunoreactive species detected using both the Tex1 and anti-RD1 antisera. It
      is suggested that the PDE4A splice variant RD1 contains a membrane-association
      signal which allows the targeted expression of RD1 within the Golgi complex of
      these human follicular thyroid carcinoma cell lines.

PMID- 9003418
TI  - Isomerization of the free enzyme versus induced fit: effects of steps involving
      induced fit that bypass enzyme isomerization on flux ratios and countertransport.
AB  - In a single-substrate-single-product enzyme reaction, "counter transport', which
      indicates that the ratio of the forward to the reverse fluxes is less than that
      expected from the Independence Relationship, is regarded as strong evidence for
      the free enzyme existing in two states, one of which combines with the substrate
      and the other with the product, with a slow isomerization between the two
      conditions. To account for positive and negative co-operativity, found with some
      enzymes, additional induced-fit reactions bypassing at least part of the
      isomerization have been proposed. The effects of such additional steps have been
      examined, using two models: in one, (a), the enzyme passes through an
      intermediate state during its isomerization, and both substrate and product may
      react with this state to give rise to the binary complexes; in the other, (b),
      the substrate may react with the enzyme as soon as the product is released and
      similarly with the reverse reaction, the isomerization thereby being bypassed
      completely. In the presence of such additional steps, the following can be
      concluded. (i) The data should be analysed in terms of the flux ratios, rather
      than observation of the amount of countertransport. (ii) The additional bypassing
      steps markedly change the pattern of dependence of the flux ratio on substrate
      and product concentrations. At high substrate and product concentrations, the
      ratio remains very dependent on how far the reaction is from equilibrium, and the
      kinetics are asymmetric. (iii) The mechanism causing the flux ratio to be less
      than that given by the Independence Relationship differs from that previously
      described, in that, at least in part, it arises from a 1:1 exchange between
      substrate and product. (iv) Despite this novel mechanism, there must be two
      states of the enzyme, combining respectively with substrate and product, and
      these must not be in rapid exchange. Thus countertransport remains very strong
      evidence for the existence of two such states. It is no longer a requirement that
      the enzyme states should be linked by an isomerization step. (v) Under no
      conditions can the flux ratio exceed that given by the Independence Relationship.
      (vi) Under unusual conditions the isomerization of the enzyme in model (b) may be
      undetectable by steady-state kinetics. (vii) Measurements of the coefficients in
      the flux ratio equations enable limits to be set to certain ratios of the rate
      constants. In addition to these conclusions, methods are described for (viii)
      analysing flux ratio data for the presence of induced fit steps and (ix)
      determining flux ratios from induced transport curves. The derivation of steady
      state-velocity equations show that: (x) both models may give rise to positive and
      negative 'co-operativity' and sigmoid substrate-velocity curves, but that, under
      conditions giving rise to sigmoid curves, the deviation of the flux ratio from
      that required by the Independence Relationship may be difficult to demonstrate
      because of the asymmetry of the system. Under all conditions the fluxes at
      equilibrium should obey hyperbolic kinetics.

PMID- 9003419
TI  - Hyperprolinaemia caused by novel members of the adipokinetic hormone/red pigment
      concentrating hormone family of peptides isolated from corpora cardiaca of
      onitine beetles.
AB  - Two novel members of the adipokinetic hormone/red pigment-concentrating hormone
      family of peptides were identified in dung beetles of the genus Onitis using
      heterologous (measuring lipid and carbohydrate mobilization in locusts and
      cockroaches) and a homologous (measuring proline increase in the haemolymph)
      bioassay(s). Isolation of the peptides was achieved by single-step reverse-phase
      HPLC of corpora cardiaca extracts. The primary structure was elucidated by
      automated Edman degradation and by electrospray MS. Both peptides are blocked
      octapeptides containing three aromatic amino acids. Peptide 1, designated Ona-CC
      I, is pGlu-Tyr-Asn-Phe-Ser-Thr-Gly-Trp-NH2, and peptide 2, designated Ona-CC-II,
      is pGlu-Phe-Asn-Tyr-Ser-Pro-Asp-Trp-NH2. The synthetic peptides were
      chromatographically indistinguishable from the natural compounds. They both had a
      hyperprolinaemic effect in the dung beetle. Moreover, flight experiments
      established that proline is an important fuel to power flight metabolism in
      Onitis species. Therefore, it is concluded that these novel and unique peptides
      are involved in regulating proline-based flight metabolism.

PMID- 9003420
TI  - Identification of an essential cysteine residue in human glutathione synthase.
AB  - Glutathione is essential for a variety of cellular functions, and is synthesized
      from gamma-glutamylcysteine and glycine by the action of glutathione synthase (EC
      6.3.2.3). Human glutathione synthase is a dimer of two identical subunits, each
      composed of 474 amino acids. Little is known about the structure-function
      relationships of mammalian glutathione synthases and, in order to gain a greater
      understanding of this critical enzyme, we have probed the role of cysteine
      residues by chemical modification and site-directed mutagenesis. Preincubation
      with thiol reagents such as p-chloromercuribenzoate, N-ethylmaleimide,
      iodoacetate and 5,5'-dithiobis-(2-nitrobenzoate) resulted in significant
      inhibition of recombinant human glutathione synthase. Each subunit contains
      cysteine residues at positions 294, 409 and 422, and we have prepared four
      different mutants by replacing individual cysteine residues, or all of the
      cysteine residues, with alanine. The C294A and C409A cysteine mutants retained
      significant residual activity, indicating that these two cysteine residues are
      not essential for activity. In contrast, substantial decreases in enzymic
      activity were detected with the C422A and cysteine-free mutants. This suggests
      that Cys-422 may play a significant structural or functional role in human
      glutathione synthase.

PMID- 9003421
TI  - Involvement of Ca2+/calmodulin-dependent protein kinase II in the activation of
      carnitine palmitoyltransferase I by okadaic acid in rat hepatocytes.
AB  - The present work was undertaken to study the mechanism by which okadaic acid
      (OA), an inhibitor of protein phosphatases 1 and 2A, stimulates carnitine
      palmitoyltransferase I (CPT-I) in isolated rat hepatocytes [Guzman, Kolodziej,
      Caldwell, Costorphine and Zammit (1994) Biochem. J. 300, 693-699]. The OA-induced
      stimulation of CPT-I was abolished by the general protein kinase inhibitor K-252a
      as well as by KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein
      kinase II (Ca2+/CM-PKII). However, neither the protein kinase C-specific
      inhibitor bisindolylmaleimide nor the protein kinase A/protein kinase C inhibitor
      H-7 was able to prevent the OA-induced stimulation of CPT-I. Hepatocyte-shrinkage
      induced stimulation of CPT-I as well as OA-induced hepatocyte shrinkage was
      prevented by KN-62. KN-62 also antagonized the OA-enhanced release of lactate
      dehydrogenase from digitonin-permeabilized hepatocytes. Exposure of 32P-labelled
      hepatocytes to OA increased the degree of phosphorylation of Ca2+/CM-PKII, as
      immunoprecipitated by a monoclonal antibody raised against the alpha-subunit of
      rat brain kinase. This effect of OA was also antagonized by KN-62. The results
      thus indicate that the OA-dependent stimulation of CPT-I may be mediated (at
      least in part) by increased phosphorylation and subsequent activation of Ca2+/CM
      PKII.

PMID- 9003423
TI  - Glucose induces the translocation of glycogen synthase to the cell cortex in rat
      hepatocytes.
AB  - After incubation with glucose a dramatic change in the intracellular distribution
      of glycogen synthase was observed in rat hepatocytes. Confocal laser scanning
      microscopy showed that glycogen synthase existed diffusely in the cytosol of
      control cells, whereas in cells incubated with glucose it accumulated at the cell
      periphery. Colocalization analysis between glycogen synthase immunostaining and
      actin filaments showed that the change in glycogen synthase distribution induced
      by glucose correlated with a marked increase in the co-distribution of the two
      proteins, indicating that, in response to glucose, glycogen synthase moves to the
      actin-rich area close to the membrane. When glycogen synthase was immunostained
      with rabbit anti-(glycogen synthase) and Protein A-colloidal gold, few particles
      were observed close to the membrane in control cells. In contrast, in cells
      incubated with glucose most of the gold particles were found near the membrane,
      confirming that glycogen synthase had moved to the cell cortex. Furthermore, in
      agreement with the glycogen synthase distribution, glycogen deposition appeared
      to be more active at the periphery of the cell.

PMID- 9003422
TI  - A novel method for the study of autophagy: destruction of hepatocytic lysosomes,
      but not autophagosomes, by the photosensitizing porphyrin tetra(4
      sulphonatophenyl)porphine.
AB  - A photoactivatable porphyrin, tetra(4-sulphonatophenyl)porphine (TPPS4), was
      shown to accumulate in rat hepatocytes as a linear function of dose after
      intravenous injection, and to localize predominantly in hepatocytic lysosomes. A
      major fraction of the lysosomal enzymes acid phosphatase and N-acetyl-beta-D
      glucosaminidase was inactivated by TPPS4 after 20 h of contact with the drug in
      vivo in the absence of photoactivation. On exposure of isolated hepatocytes to
      light, photoactivated TPPS4 caused additional inactivation of the lysosomal
      enzymes as well as inactivation of intralysosomal lactate dehydrogenase (LDH), a
      cytosolic enzyme that accumulated in lysosomes as a result of autophagy during a
      2 h incubation of hepatocytes at 37 degrees C in the dark (in the presence of the
      proteinase inhibitor leupeptin to prevent degradation of intralysosomal LDH).
      Photoactivation of TPPS4 also induced lysosomal rupture, with a loss of lysosomal
      enzymes, autophagocytosed LDH, endocytosed 125I-tyramine-cellobiose-asialo
      orosomucoid and TPPS4 from the lysosomes. However, LDH-containing autophagosomes,
      accumulated in the presence of vinblastine (a microtubule inhibitor used to
      prevent the fusion of lysosomes with autophagosomes or endosomes), were not
      affected by TPPS4. TPPS4 may thus be useful as a selective lysosomal (or
      endosomal) perturbant in the study of autophagic-endocytic-lysosomal
      interactions.

PMID- 9003424
TI  - Proteolytic cleavage of cellubrevin and vesicle-associated membrane protein
      (VAMP) by tetanus toxin does not impair insulin-stimulated glucose transport or
      GLUT4 translocation in rat adipocytes.
AB  - Acute insulin stimulation of glucose transport in fat and skeletal muscle occurs
      principally as a result of the hormonal induced translocation of the GLUT4
      glucose transporter from intracellular vesicular stores to the plasma membrane.
      The precise mechanisms governing the fusion of GLUT4 vesicles with the plasma
      membrane are very poorly understood at present but may share some similarities
      with synaptic vesicle fusion, as vesicle-associated membrane protein (VAMP) and
      cellubrevin, two proteins implicated in the process of membrane fusion, are
      resident in GLUT4-containing vesicles isolated from rat and murine 3T3-L1
      adipocytes respectively. In this study we show that proteolysis of both
      cellubrevin and VAMP, induced by electroporation of isolated rat adipocytes with
      tetanus toxin, does not impair insulin-stimulated glucose transport or GLUT4
      translocation. The hormone was found to stimulate glucose uptake by approx. 16
      fold in freshly isolated rat adipocytes. After a single electroporating pulse,
      the ability of insulin to activate glucose uptake was lowered, but the observed
      stimulation was nevertheless nearly 5-fold higher than the basal rate of glucose
      uptake. Electroporation of adipocytes with 600 nM tetanus toxin resulted in a
      complete loss of both cellubrevin and VAMP expression within 60 min. However,
      toxin-mediated proteolysis of both these proteins had no effect on the ability of
      insulin to stimulate glucose transport which was elevated approx. 5-fold, an
      activation of comparable magnitude to that observed in cells electroporated
      without tetanus toxin. The lack of any significant change in insulin-stimulated
      glucose transport was consistent with the finding that toxin-mediated proteolysis
      of both cellubrevin and VAMP had no detectable effect on insulin-induced
      translocation of GLUT4 in adipocytes. Our findings indicate that, although
      cellubrevin and VAMP are resident proteins in adipocyte GLUT4-containing
      vesicles, they are not required for the acute insulin-induced delivery of GLUT4
      to the plasma membrane.

PMID- 9003425
TI  - Investigation on the mechanism by which fructose, hexitols and other compounds
      regulate the translocation of glucokinase in rat hepatocytes.
AB  - In isolated hepatocytes in suspension, the effect of sorbitol but not that of
      fructose to increase the concentration of fructose 1-phosphate and to stimulate
      glucokinase was abolished by 2-hydroxymethyl-4-(4-N,N-dimethylamino-1-piperazino)
      pyrimidine (SDI 158), an inhibitor of sorbitol dehydrogenase. In hepatocytes in
      primary culture, fructose was metabolized at approximately one-quarter of the
      rate of sorbitol, and was therefore much less potent than the polyol in
      increasing the concentration of fructose 1-phosphate and the translocation of
      glucokinase. In cultures, sorbitol, commercial mannitol, fructose, D
      glyceraldehyde or high concentrations of glucose caused fructose 1-phosphate
      formation and glucokinase translocation in parallel. Commercial mannitol was
      contaminated by approx. 1% sorbitol, which accounted for its effects. The effects
      of sorbitol, fructose and elevated concentrations of glucose were partly
      inhibited by ethanol, glycerol and glucosamine. Mannoheptulose increased
      translocation without affecting fructose 1-phosphate concentration. Kinetic
      studies performed with recombinant human beta-cell glucokinase indicated that
      this sugar, in contrast with N-acetylglucosamine, binds to glucokinase
      competitively with the regulatory protein. All these observations indicate that
      translocation is promoted by agents that favour the dissociation of the
      glucokinase-regulatory-protein complex either by binding to the regulatory
      protein (fructose I-phosphate) or to glucokinase (glucose, mannoheptulose). They
      support the hypothesis that the regulatory protein of glucokinase acts as an
      anchor for this enzyme that slows down its release from digitonin-permeabilized
      cells.

PMID- 9003427
TI  - Identification and characterization of the 2-enoyl-CoA hydratases involved in
      peroxisomal beta-oxidation in rat liver.
AB  - In this study we attempted to determine the number of 2-enoyl-CoA hydratases
      involved in peroxisomal beta-oxidation. We therefore separated peroxisomal
      proteins from rat liver on several chromatographic columns and measured hydratase
      activities on the eluates with different substrates. The results indicate that
      rat liver peroxisomes contain two hydratase activities: (1) a hydratase activity
      associated with multifunctional protein 1 (MFP-1) (2-enoyl-CoA hydratase/delta 3,
      delta 2-enoyl-CoA isomerase/L-3-hydroxyacyl-CoA dehydrogenase) and (2) a
      hydratase activity associated with MFP-2 (17 beta-hydroxysteroid dehydrogenase/D
      3-hydroxyacyl-CoA dehydrogenase/2-enoyl-CoA hydratase). MFP-1 forms and
      dehydrogenates L-3-hydroxyacyl-CoA species, whereas MFP-2 forms and
      dehydrogenates D-3-hydroxyacyl-CoA species. A portion of MFP-2 is proteolytically
      cleaved, most probably in the peroxisome, into a 34 kDa 17 beta-hydroxysteroid
      dehydrogenase/D-3-hydroxyacyl-CoA dehydrogenase and a 45 kDa D-specific 2-enoyl
      CoA hydratase. Finally, the results confirm that MFP-1 is involved in the
      degradation of straight-chain fatty acids, whereas MFP-2 and its cleavage
      products seem to be involved in the degradation of the side chain of cholesterol
      (bile acid synthesis).

PMID- 9003426
TI  - The MAL proteolipid is a component of the detergent-insoluble membrane subdomains
      of human T-lymphocytes.
AB  - The human mal gene, identified during a search for cDNAs selectively expressed
      during T-cell development, encodes a highly hydrophobic protein belonging to a
      group of proteins, termed proteolipids, characterized by their unusual property
      of being soluble in organic solvents used to extract cell lipids. To study the
      localization of the MAL protein we have prepared stable transfectants expressing
      the MAL protein tagged with a c-myc epitope (MAL/c-myc) using human epithelial A
      498 cells. Immunofluorescence analysis suggested that MAL/c-myc is localized
      mainly to cholesterol-enriched structures with a post-Golgi location and, at low
      levels, in early endosomes. Moreover, extraction of A-498 cell membranes with
      Triton X-100 (TX100) and fractionation by centrifugation to equilibrium in
      sucrose gradients demonstrated the presence of MAL/c-myc in the detergent
      insoluble buoyant fraction, known to be enriched in glycolipids and cholesterol.
      To compare the behaviour of MAL in T-cells with that in epithelial A-498 cells,
      we prepared stably transfected cells expressing MAL/c-myc using human Jurkat T
      cells. When TX100 extracts from Jurkat cells were subjected to centrifugation to
      equilibrium in sucrose gradients we found MAL exclusively in the floating
      fractions, together with molecules characteristic of the T-cell insoluble
      complexes, such as the tyrosine kinase p56lck, the glycosylphosphatidylinositol
      anchored protein CD59 and the ganglioside GM1. These results, taken together,
      indicate that the MAL proteolipid is a component of the detergent-resistant
      membrane microdomains present in T-lymphocytes, and suggest that MAL might play a
      role in modulating the function of these microdomains during T-cell
      differentiation.

PMID- 9003429
TI  - Binding of [3H]bilirubin to albumin and plasma membrane vesicles.

PMID- 9003428
TI  - The case of chicken attachment region binding protein reinforces the importance
      of pre-screening of several libraries for cDNA cloning.

PMID- 9003430
TI  - Complete amino-acid sequence of the beta-subunit of VTX from venom of the
      stonefish (Synanceia verrucosa) as identified from cDNA cloning experiments.
AB  - A cDNA encoding a subunit of the verrucotoxin (VTX) has been identified from a
      cDNA library derived from stonefish venom glands. It encodes a polypeptide of 708
      amino-acid residues, followed by a 3'-untranslated region of 895 bp long. The ORF
      contains the complete mature sequence of the beta-subunit of the VTX, as inferred
      from both the presence of an identical N-terminus sequence and 96% homology among
      the 506 amino terminus residues found in the partial sequence of the beta-subunit
      of the stonustoxin from Synanceia horrida (Ghadessy, F.J., Jeyaseelan, K., Chung,
      M.C.M., Khoo, H.E., and Yuen, R. (1994) Toxicon 32, 1684-1688). Upstream the
      mature sequence, we noticed the presence of an incomplete peptide of a 13 amino
      acids, whose unusual primary structure supports the idea of the existence of a
      propeptide and/or of a new secretion signal.

PMID- 9003431
TI  - Cloning and sequencing of cDNA encoding NG,NG-dimethylarginine
      dimethylaminohydrolase from rat kidney.
AB  - Three cDNA clones encoding NG,NG-dimethylarginine dimethylamino-hydrolase (EC
      3.5.3.18) have been isolated from a rat kidney lambda gt11 library using a probe
      prepared by PCR on the basis of partially determined amino-acid sequences of the
      enzyme. The sequence analyses of the cDNAs established that the 3008 bp cDNA
      contains 855 bp open reading frame encoding 285 amino acids (M(r) 31414), 3'
      flanking region (1722 bp) and 5'-flanking region (431 bp). The amino-acid
      sequences of all the peptides isolated from the purified enzyme were shown to be
      included in the deduced amino-acid sequence. Northern blotting analyses showed
      that the mRNA (4 kb) is ubiquitously expressed in various rat tissues.

PMID- 9003432
TI  - An electron paramagnetic resonance study on the mechanism-based inactivation of
      adenosylcobalamin-dependent diol dehydrase by glycerol and other substrates.
AB  - Adenosylcobalamin-dependent diol dehydrase undergoes mechanism-based inactivation
      by glycerol or other substrates during catalysis. X-band electron paramagnetic
      resonance spectra of holoenzyme were measured at -130 degrees C after reaction
      with such substrates. After short time of incubation, broad signals assigned to
      low-spin Co(II) of cob(II)alamin and doublet signals assigned to an organic
      radical intermediate derived from each substrate were observed with 1,2
      propanediol, 1,2-ethanediol, glycerol and meso-2,3-butanediol with the magnitude
      of their exchange interaction (J-value) decreasing in this order. A substrate
      with the smaller magnitude of exchange interaction between low-spin Co(II) and an
      organic radical intermediate seems to be an efficient mechanism-based
      inactivator. Since the magnitude of exchange interaction decreases with the
      distance between radical species in a radical pair, these results suggest that a
      stabilizing effect of holoenzyme on radical intermediates during reactions
      decreases with the distance between Co(II) and a radical.

PMID- 9003433
TI  - A contact scoring matrix for qualitative prediction of change in folding of alpha
      helices in globular proteins caused by a mutation.
AB  - The atomic pairs in contact for atoms from pairs of amino-acid residues on pairs
      of helices in a protein database consisting of 48 proteins of known tertiary
      structure from the Brookhaven Protein Data Bank are searched and counted to
      construct a primary scoring system. Each score in the primary scoring system is
      weighted further with the possibility of occurrence of each residue pair in the
      protein database to give a final scoring matrix. Scores for predicting change in
      folding of alpha-helices in a mutant protein are calculated by assuming that
      every pair of helices in the protein can closely interact with each other. It is
      shown that the change in folding of alpha-helices in several mutant proteins are
      reflected in both the change of the contact scores and the helix geometry
      calculated.

PMID- 9003434
TI  - The human ENO1 gene product (recombinant human alpha-enolase) displays
      characteristics required for a plasminogen binding protein.
AB  - Plasminogen binds with low affinity in a lysine-dependent manner to many cell
      types. Previously, a 54 kDa plasminogen receptor found on the surface of U-937
      cells was identified as an alpha-enolase-like molecule. The aims of this study
      were to determine whether recombinant alpha-enolase (r-alpha-enolase), encoded by
      ENO1, was a plasminogen binding protein and to generate polyclonal antibodies
      against this antigen. Plasminogen specifically bound r-alpha-enolase with a Kd
      1.9 microM and approached saturation at 10 microM. Lysine-dependent plasminogen
      binding to r-alpha-enolase was demonstrated by a greater than 80% inhibition of
      binding by the lysine analogues epsilon-amino caproic acid and tranexamic acid,
      whilst only 14% inhibition occurred with the arginine analogue benzamidine.
      Removal of the C-terminal lysine residue of r-alpha-enolase with carboxy
      peptidase B significantly reduced its plasminogen binding capacity, suggesting
      that binding required C-terminal lysine residue of r-alpha-enolase. Binding to r
      alpha-enolase enhanced the activation rate of plasminogen by urokinase but
      prevented alpha 2-antiplasmin from binding plasminogen. Taken together, these
      data suggest that the gene product of human ENO1 encodes an authentic plasminogen
      binding protein.

PMID- 9003435
TI  - A unique enzyme from Saccharothrix sp. catalyzing D-amino acid transfer.
AB  - A newly isolated actinomycete belonging to Saccharothrix sp. was found to produce
      a unique enzyme catalyzing D-amino acid transfer. The enzyme, which was
      tentatively named D-amino acid transferase, was purified 2600-fold to
      electrophoretic homogeneity and the molecular mass was 41 kDa. The enzyme was D
      configuration specific and recognized aromatic D-amino acid esters to form oligo
      D-amino acid esters. D-Phenylalanine ester was favored as substrate over other D
      amino acid esters. The optimum conditions for oligo D-phenylalanine ester
      formation by D-amino acid transferase were pH 7.0 and 40 degrees C. The enzyme
      was inhibited by DAN, EPNP and DFP.

PMID- 9003436
TI  - Role of the amino terminal domain in GroES oligomerization.
AB  - Digestions of the GroES oligomer with trypsin, chymotrypsin and Glu-C protease
      from Staphylococcus aureus V8 (V8) have helped to locate three regions in the
      GroES sequence that are sensitive to limited proteolysis and have provided
      information of the GroES domains involved in monomer-monomer and GroEL
      interaction. The removal of the first 20 or 27 amino acids of the N-terminal
      region of each GroES monomer by trypsin or chymotrypsin respectively, abolish the
      oligomerization of the GroES complex and its binding to GroEL. The V8-treatment
      of GroES promotes the breakage of the peptide bond between Glu18 and Thr19 but
      not the liberation of the N-terminal fragment from the GroES oligomer, which is
      capable of forming with GroEL a complex active in protein folding. It is deduced
      from these results that the N-terminal region of the GroES monomer is involved in
      monomer-monomer interaction, providing experimental evidence that relates some
      biochemical properties of GroES with its three-dimensional structure at atomic
      resolution.

PMID- 9003438
TI  - Absorption spectral studies on heme ligand interactions of P-450nor.
AB  - Heme-external ligand interactions of P-450nor were examined
      spectrophotometrically and compared with those of other P-450s. Most nitrogenous
      ligands induced type II spectral changes on binding to ferric P-450nor, as did
      other P-450s. In contrast with other P-450s, 2-methylpyridine and 1-butanol
      induced type I changes in the spectrum of P-450nor. No spectral interaction of
      ferrous P-450nor with these ligands was observed. The absorption spectra of the
      alkyl isocyanide complexes of ferrous P-450nor exhibited the Soret peak at 427 nm
      with a slight shoulder at around 455 nm at neutral pH, and this shoulder was
      intensified as the pH was increased, suggesting that the isocyanide complexes of
      P-450nor existed in two states (the 430 and 455 nm states) which were in pH
      dependent equilibrium in a similar manner to microsomal P-450s. However, the
      equilibrium was shifted mostly to the 430 nm state in the complexes of P-450nor.
      The findings suggest that P-450nor, especially its ferrous form, has some
      distinct features from P-450cam and microsomal P-450s in the distal heme
      environment.

PMID- 9003437
TI  - Purification and properties of a lipid transfer particle from Bombyx mori:
      comparison to the lipid transfer particle from Manduca sexta.
AB  - A lipid transfer particle (LTP) was purified from the hemolymph of the silkworm
      Bombyx mori. Like other insect LTPs, the B. mori LTP is a very high density
      lipoprotein containing 21% lipid and three apoproteins of mass approximately 350
      kDa, approximately 85 kDa, and approximately 60 kDa. B. mori LTP catalyzes the
      exchange of lipids between different density class lipoproteins found in adult
      hemolymph and between adult lipoproteins and vitellogenin. However, in no case
      was net lipid transfer observed. Manduca sexta LTP also catalyzed exchange of
      lipids, but not net transfer of lipids, between different density class
      lipoproteins found in adult hemolymph.

PMID- 9003439
TI  - Kinetic characterization of all steps of the interaction between
      acetylcholinesterase and eserine.
AB  - The three-step carbamylenzyme mechanism of the action of eserine on
      acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) has been known
      for a long time, but its complete kinetic characterization has never been done.
      Some of our investigations indicated that the determination of missing kinetic
      parameters should include the inspection of the enzyme-eserine interaction in a
      very wide range of eserine concentrations. Therefore, the activity of
      acetylcholinesterase as a function of time in the presence of low concentrations
      of eserine comparable to the enzyme concentration was followed. The reaction
      mechanism was analysed by fitting numerically integrated differential equations
      that describe the time dependences of all reactants and reaction intermediates to
      these data. Additionally, the progress curve measurements at higher eserine
      concentrations were carried out on a stopped-flow apparatus. The corresponding
      progress curve equations were derived and the kinetic parameters evaluated by non
      linear regression treatment. The complex analysis confirmed the three-step
      mechanism. The values of the constants showed that the very high affinity of
      eserine for binding into the active centre of the enzyme is not so much a
      consequence of the fast initial complex formation but rather a consequence of its
      slow dissociation. The subsequent covalent bonding of eserine is also slow, but
      faster than the dissociation of the initial complex. In this manner, the
      decarbamoylation is the only process responsible for the reactivation of
      acetylcholinesterase after removal of eserine.

PMID- 9003441
TI  - Biphasic nature in the autoxidation reaction of human oxyhemoglobin.
AB  - In comparison with myoglobin molecule as a reference, we have studied the
      autoxidation rate of human oxyhemoglobin (HbO2) as a function of its
      concentration in 0.1 M buffer at 35 degrees C and in the presence of 1 mM EDTA.
      At pH 6.5, HbA showed a biphasic autoxidation reaction that can be described
      completely by a first-order rate equation containing two rate constants-kf, for
      fast autoxidation of the alpha-chain, and ks, for slow autoxidation of the beta
      chain, respectively. When tetrameric HbO2 was dissociated into alpha beta-dimers
      by dilution, the value of kf increased markedly to an extent comparable with the
      autoxidation rate of horse heart oxymyoglobin (MbO2). The rate constant Ks, on
      the other hand, was found to remain at an almost constant value over the whole
      concentration range from 1.0 x 10(-3) M to 3.2 x 10(-6) M in heme. At pH 8.5 and
      pH 10.0, however, the autoxidation of HbO2 was monophasic, and no enhancement in
      the rate was observed by diluting hemoglobin solutions. Taking into consideration
      the effects of 2,3-diphosphoglyceric acid and chloride anion on the autoxidation
      rate of HbO2, we have characterized the differential susceptibility of the alpha-
      and beta-chains to the autoxidation reaction in aqueous solution.

PMID- 9003440
TI  - Purification and characterization of hepsin from rat liver microsomes.
AB  - Hepsin, a putative cell-surface serine proteinase, has been isolated from the
      microsomal membranes of rat liver and purified to homogeneity by hydroxyapatite,
      DEAE-Sepharose, and benzamidine-Sepharose chromatography. The course of
      purification was monitored using antibodies raised against a 20-mer peptide at
      the C-terminus of rat hepsin, and the identity of the purified protein was
      confirmed by partial amino-acid sequencing. A single-chain precursor of ca. 50
      kDa found in the microsomes underwent spontaneous maturation in the course of
      purification so that the last, affinity chromatography, step recovered only the
      mature form which dissociated to subunits of 31 and 19 kDa under reducing SDS
      PAGE. Proteinase digestion experiments with microsomal vesicles are consistent
      with the luminal orientation of the precursor C-terminus, which would result in
      its extracellular orientation upon transportation to the cell surface.
      [3H]diisopropylfluorophosphate covalently binds to the large subunit showing it
      to be the catalytic one. The N-terminal sequencing of this subunit demonstrates
      that the zymogen is converted to the active serine proteinase by cleavage at the
      Arg161-Ile162 site. Activity measurements with short synthetic peptides show that
      the enzyme cleaves after basic amino-acid residues, Arg being preferable to Lys.
      The inhibition pattern is typical of trypsin-like serine proteinases. The pH
      dependence of activity within the range pH 6-9 has no maximum, the activity
      increasing continuously with pH. These results are consistent with the earlier
      predictions based on hepsin amino-acid sequence and elucidate the specificity and
      other earlier unknown enzymatic and molecular properties of the enzyme.

PMID- 9003442
TI  - Purification, catalytic properties and thermostability of 3-isopropylmalate
      dehydrogenase from Escherichia coli.
AB  - 3-isopropylmalate dehydrogenase (IPMDH) from Escherichia coli was overexpressed,
      purified and crystallized. The enzyme was characterized and compared to its
      thermophilic counterpart from Thermus thermophilus strain HB8. As in the
      thermophile enzyme, the activity of E. coli IPMDH was dependent on the divalent
      cations, Mg2+ or Mn2+, with Mn2+ being the preferred cation. Activity was also
      strongly influenced by KCl: 0.3 M were necessary for the optimal activity. At 40
      degrees C the K(m) of E. coli IPMDH was 105 microM for IPM and 321 microM for
      NAD, the kcat was 69 s-1. The half denaturation temperature was 64 degrees C,
      which was 20 degrees C lower than that of the thermophile enzyme.

PMID- 9003443
TI  - A 3-hydroxy-3-methylglutaryl-CoA lyase gene in the photosynthetic bacterium
      Rhodospirillum rubrum.
AB  - A 1.2 kb long DNA segment from Rhodospirillum rubrum has been sequenced
      (EMBL/GenBank accession number: U41280). This DNA segment includes the first
      sequenced gene for a putative 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase,
      termed hmgL, from a photosynthetic organism. The sequenced segment also contains
      a ribosome-binding site and two clusters of possible-35 and -10 promotor
      sequences preceding the hmgL gene. Translation of the gene would yield a 303
      amino-acid-long protein with a calculated molecular weight of 31.1 kDa. This
      protein shows 55-60% identity and approx. 75% similarity, including conservative
      substitutions, with the three eukaryotic and the single prokaryotic HMG-CoA
      lyases which previously have been sequenced. The R. rubrum enzyme showed stronger
      homology to the chicken HMG-CoA lyase than to the other bacterial protein.
      Significant sequence similarity was also found with homocitrate synthases from
      nitrogen-fixing prokaryotes. In contrast to the other sequenced prokaryotic HMG
      CoA lyase (from Pseudomonas mevalonii), the R. rubrum hmgL does not seem to
      appear in an operon together with a HMG-CoA reductase. The hmgL gene was
      transcribed in photosynthetically grown cells as judged by amplification of cDNAs
      synthesised from DNA-free total RNA. In addition, HMG-CoA lyase activity was
      found in R. rubrum cells grown anaerobically in the light with leucine as the
      carbon source.

PMID- 9003444
TI  - Purification, characterization and activities of two hemolytic and antibacterial
      proteins from coelomic fluid of the annelid Eisenia fetida andrei.
AB  - The coelomic fluid of the earthworm Eisenia fetida andrei exhibits antibacterial,
      hemolytic and hemagglutinating activities. These activities are mainly mediated
      by two proteins, named fetidins, of apparent molecular mass 40 kDa and 45 kDa,
      respectively. For the first time, the two proteins have been purified to
      homogeneity from dialysed coelomic fluid by means of anion-exchange
      chromatography. Three peaks had hemolytic activity. The first fraction was found
      to correspond to the 40 kDa fetidin, the second to mixed 40 and 45 kDa fetidins,
      the last one to the 45 kDa fetidin. Both purified proteins still exhibited their
      hemolytic and antibacterial activities as dialysed coelomic fluid did. In this
      study, the amino-acid sequence of purified proteins is compared to the amino-acid
      sequence predicted by cDNA. This cDNA was isolated by screening an expression
      cDNA library from earthworm total tissues (unpublished data).

PMID- 9003445
TI  - Purification and characterization of D(+)-carnitine dehydrogenase from
      Agrobacterium sp.--a new enzyme of carnitine metabolism.
AB  - D(+)-Carnitine dehydrogenase from Agrobacterium sp. catalyzes the oxidation of
      D(+)-carnitine to 3-dehydrocarnitine as initial step of D(+)-carnitine
      degradation. The NAD(+)-specific, cytosolic enzyme was purified 126-fold to
      apparent electrophoretic homogeneity by 4 chromatographic steps. The molecular
      mass of the native enzyme was estimated to be 88 kDa by size-exclusion
      chromatography. It seems to be composed of 3 identical subunits with a relative
      molecular mass of 28 kDa as found by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis and laser-induced mass spectrometry. The isoelectric point was
      found to be 4.7-5.0. The optimum temperature is 37 degrees C and the optimum pH
      for the oxidation and the reduction reaction are 9.0-9.5 and 5.5-6.5,
      respectively. The purified enzyme was further characterized with respect to
      substrate specificity, kinetic parameters and amino terminal sequence. Analogues
      of D(+)-carnitine (L(-)-carnitine, crotonobetaine, gamma-butyrobetaine, carnitine
      amide, glycine betaine, choline) are competitive inhibitors of D(+)-carnitine
      oxidation. The equilibrium constant of the reaction of D(+)-carnitine
      dehydrogenase was determined to be 2.2 x 10(-12). The purified D(+)-carnitine
      dehydrogenase has similar kinetic properties to the L(-)-carnitine dehydrogenase
      from the same microorganism as well as to L(-)-carnitine dehydrogenases of other
      bacteria.

PMID- 9003446
TI  - Additional data about thermolysin specificity in buffer- and glycerol-containing
      media.
AB  - Synthesis and use of various substrates permit an improved approach to
      thermolysin-peptide recognition and elucidation of several new criteria affecting
      enzyme specificity. Nature and position of the recognized residue, role of
      adjacent amino acids, lateral chain hydrophobicity, and volume and length of
      peptides were all considered. Hydrolysis reactions were also carried out in the
      presence of glycerol; the effect of microenvironment modifications was
      quantitative, for example in inducing variations in catalytic reaction rates, and
      also qualitative, such as in influencing affinity.

PMID- 9003447
TI  - Role of the O-phosphoserine clusters in the interaction of the bovine milk alpha
      s1-, beta-, kappa-caseins and the PP3 component with immobilized iron (III) ions.
AB  - alpha s1- and beta-Caseins have a sequence cluster -Ser(P)-Ser(P)-Ser(P)-Glu-Glu-
      which is not present in kappa-casein and the whey PP3 component. The affinity of
      these phosphoproteins for the iron(III)-iminodiacetic acid (IDA) complex
      immobilized on Sepharose was studied as a function of pH, urea concentration,
      calcium ion concentration, enzymatic dephosphorylation and temperature. The
      affinity of the three polyphosphorylated proteins (alpha s1- and beta-caseins,
      PP3) was similar. The sequence cluster was not a specific recognition pattern of
      the iron(III) ion. These three proteins presented a site of high affinity and a
      site of weak affinity. kappa-Casein, which had only one Ser(P) residue, presented
      only the site of weak affinity. Their primary site which was absent after
      dephosphorylation or calcium ion addition required the presence of at least two
      Ser(P) residues close in space. Their secondary site was sensitive to the
      presence of urea. It was sensitive to pH variation for PP3 and kappa-casein. The
      study of the affinity of a few free amino acids towards iron(III)-IDA showed that
      the secondary site involved tryptophan and tyrosine residues for alpha s1- and
      beta-caseins, histidine residues for PP3 and cysteine residues for kappa-casein.

PMID- 9003448
TI  - Structure and transcription of the gene for translation elongation factor 1
      subunit alpha of zebrafish (Danio rerio).
AB  - The zebrafish gene for translation elongation factor 1 alpha (EF1 alpha) was
      isolated from a phage Lambda genomic library and sequence and structure
      determined. One gene copy of EF1 alpha per haploid set of chromosomes was found
      and no processed pseudogenes. A highly active promoter region was localized to a
      277 bp PstI/PvuII fragment beginning 240 bp upstream from the tsp, but no
      transcription enhancing, or silencing activity was observed within 1 kbp
      upstream, or downstream from the promoter. Expression of EF1 alpha appears to be
      developmentally regulated.

PMID- 9003449
TI  - Cloning and sequencing of rat cDNA for the 41-kDa phosphoribosylpyrophosphate
      synthetase-associated protein has a high homology to the catalytic subunits and
      the 39-kDa associated protein.
AB  - Rat liver phosphoribosylpyrophosphate synthetase is a complex aggregate of 34-kDa
      catalytic subunits (PRS I and II) and 39- and 41-kDa associated proteins (PAP39
      and 41). When the rat cDNA encoding PAP41 was isolated, the deduced protein
      sequence was seen to contain 369 amino acids with a calculated molecular mass of
      41130. PAP41 has a 79 and 49% identity with PAP39 and PRSs, respectively. When
      conservative substitutions are included, PAP41 and the three other components
      have a 66% homology. PAP41 shares some common features with PAP39 and the two
      proteins form the PAP subfamily. The mRNA of PAP41 is present in all rat tissues
      we examined.

PMID- 9003451
TI  - A novel genetic organization: the leuA-rpoD1 locus in the cyanobacterium
      Microcystis aeruginosa K-81.
AB  - We cloned and sequenced the region upstream of rpoD1, which encodes a principal
      sigma factor in the cyanobacterium Microcystis aeruginosa K-81. An open reading
      frame (orf1, 1599 bp) was discovered, the deduced amino-acid sequence of which
      (533 aa, 58, 016 Da) exhibits homology to another bacterial leuA gene product, 2
      isopropylmalate synthase. The leuA (orf1) gene specifically complemented an E.
      coli leuA mutant. The 5'-upstream region of leuA did not contain possible leader
      peptide or stem-loop structures for attenuation. These findings indicate that the
      genetic structure of the leuA-rpoD1 locus in M. aeruginosa K-81 significantly
      differs from those of known leuA and rpoD loci found in other bacteria.

PMID- 9003450
TI  - Molecular cloning of a novel trypsin-like serine protease (neurosin)
      preferentially expressed in brain.
AB  - A cDNA encoding a precursor for a novel serine protease (neurosin) was cloned
      from a cDNA library prepared from a human colon adenocarcinoma cell line, COLO
      201. The sequence consisted of 155 bp 5' non-coding region and a 732 bp open
      reading frame which was followed by a 551 bp 3' non-coding region. The predicted
      protein consists of 244 amino acids which is possibly processed to an active
      enzyme of 223 amino acids that shows some similarity (< 30%) to other members of
      serine protease family. As found in other trypsin-like proteases, the enzyme
      contains the catalytic triad which is characterized as the essential amino acid
      residues for the activity. Northern blot analyses of the mRNA showed the
      strongest expression in brain followed by a lower but significant one in spleen.
      A construct of cDNA encoding chimeric protein that carries pro-sequence of
      trypsin II and putative mature neurosin starting from Leu22 was transfected to
      COS-1 cells. Successful production of the active neurosin was shown after
      treating the supernatant of the culture of the transfectants with enterokinase.

PMID- 9003452
TI  - Novel beta 3 isoform of the Na,K-ATPase beta subunit from mouse retina.
AB  - We isolated a full-length cDNA encoding a novel 278 amino acid beta subunit of
      Na,K-ATPase from a mouse retinal cDNA library. The highest sequence identity was
      to known beta 3 isoforms, identifying the protein as the mouse beta 3 subunit of
      Na,K-ATPase. Two transcripts, 1.75 kb and 2.1 kb, probably arise from use of
      alternative poly(A) addition signals.

PMID- 9003453
TI  - An orphan nuclear receptor lacking a zinc-finger DNA-binding domain: interaction
      with several nuclear receptors.
AB  - The yeast two-hybrid screening was applied to cloning cDNAs of proteins that
      interact with peroxisome proliferator-activated receptor alpha (PPAR alpha). We
      obtained from a rat liver cDNA library a clone encoding a protein related to the
      ligand-binding domain of the members of nuclear hormone receptor superfamily,
      whereas apparently lacking the zinc-finger DNA-binding domain. This protein
      interacted with the activated forms of several nuclear receptors, and thus is a
      novel type of heterodimer-forming nuclear receptor.

PMID- 9003454
TI  - Isolation of chicken alpha ENaC splice variants from a cochlear cDNA library.
AB  - Three splice variants of the alpha subunit of the amiloride-sensitive epithelial
      sodium channel (alpha ENaC) have been isolated from a chicken cochlear cDNA
      library. A PCR product, generated from the cochlear library using degenerate
      primers to regions of homology between the rat alpha ENaC and the degenerin Mec
      4, was used as a probe. The three splice variant cDNAs with sizes of 2321, 3399
      and 3845 bp correspond to transcripts of 2.5, 3.5 and 3.9 kb as detected by
      Northern blot analysis. The 3399 bp clone differs from the 2321 clone solely by
      the addition of 1079 bases in the 3'-non-coding region. Both these cDNAs code for
      an identical predicted protein of 637 amino acids which has 68% similarity to the
      rat alpha ENaC, and is probably the chicken homologue of alpha ENaC. The third
      cDNA of 3845 bp is similar to the 3399 bp clone but includes two exons within the
      open reading frame. The first of these exons introduces a premature stop codon
      resulting in a truncated predicted protein of 434 amino acids. Northern blot
      analysis shows expression of the 2.5 and 3.5 kb transcripts in cochlea and colon,
      the 2.5 kb transcript in cartilage, whilst the 3.9 kb transcript is only detected
      in cochlea. No expression is detected in brain, liver, and heart nor, most
      notably, in lung or kidney.

PMID- 9003455
TI  - Nucleotide sequence of the Bacillus licheniformis ATCC 10716 dat gene and
      comparison of the predicted amino acid sequence with those of other bacterial
      species.
AB  - The gene encoding the D-aminotransferase from Bacillus licheniformis was cloned
      and the complete DNA sequence was determined. The deduced D-aminotransferase
      protein sequence, consists of 283 amino acids and shows a high degree of homology
      with other Bacillus D-aminotransferases, branched chain aminotransferase of
      Escherichia coli and the 4-amino-benzoate-4-deoxychorismate lyase of Bacillus
      subtilis and Escherichia coli.

PMID- 9003456
TI  - Cloning, sequencing and overexpression of the gene encoding malate dehydrogenase
      from the deep-sea bacterium Photobacterium species strain SS9.
AB  - The gene encoding malate dehydrogenase (mdhA) was obtained from the
      psychrophilic, barophilic, deep-sea isolate Photobacterium species strain SS9.
      The SS9 mdhA gene directed high levels of malate dehydrogenase (MDH) production
      in Escherichia coli. A comparison of SS9 MDH to three mesophile MDHs, a MDH
      sequence obtained from another deep-sea bacterium, and to other psychrophile
      proteins is presented.

PMID- 9003458
TI  - Regulation of the human long chain acyl-CoA dehydrogenase gene by nuclear hormone
      receptor transcription factors.
AB  - Mitochondrial fatty acid oxidation provides most of the energy required for
      myocardial function after birth. Long chain acyl-CoA dehydrogenase (LCAD)
      catalyzes the first step in the beta-oxidation spiral. Our objective was to
      define regulatory elements of the human LCAD gene required for high levels of
      expression in mature heart and to locate elements suppressing gene expression in
      the fetus. We characterized the human LCAD gene structure and used in vitro
      transfection into cardiomyocytes and hepatoma cells of LCAD genomic fragments
      fused to a reporter gene to examine the effects of putative regulatory elements
      on transcription. Binding of transcription factors to nuclear hormone receptor
      consensus DNA binding domains was studied by gel shift experiments. The 200 bp of
      the human LCAD gene immediately upstream of the transcription initiation site are
      sufficient to act as a minimal promoter for the gene and provide some tissue
      specific positive regulatory elements. The region from -1800 bp to -250 bp
      contains elements which markedly suppress transcription, including nuclear
      hormone receptor response elements. The dominant interaction is with the
      repressor factor, chicken ovalbumin upstream promoter transcription factor. We
      conclude that the developmental and tissue-specific regulation of the human LCAD
      gene is mediated, in part, by these nuclear hormone receptor transcription
      factors.

PMID- 9003457
TI  - Bone morphogenetic protein 2 transcripts in rapidly developing deer antler tissue
      contain an extended 5' non-coding region arising from a distal promoter.
AB  - To understand the regulation of the BMP-2 gene expression, we recently isolated
      the BMP-2 gene from a mouse genomic library and characterized the exon-intron
      structure and promoter. RNase protection assay using poly (A)+ RNA of mouse
      osteoblasts demonstrates that two regions in BMP-2 gene are protected by
      antisense mouse BMP-2 RNA probes. These results demonstrate that BMP-2 gene
      utilizes two alternative promoters, a distal and a proximal promoter. In the
      present study we demonstrate that BMP-2 mRNA from rapidly growing deer antler
      tissue has an extended 5' non-coding region compared with the human and rat BMP-2
      mRNA. The extended 5' non-coding region in the deer mRNA represents transcripts
      from the upstream distal promoter. This is the first evidence of a natural BMP-2
      mRNA from a bone-forming tissue that most likely initiated from the distal
      transcription start site.

PMID- 9003459
TI  - Structural organization and characterization of the promoter region of a human
      carboxylesterase gene.
AB  - A gene encoding a human liver carboxylesterase has been isolated and
      characterized. Analysis of three overlapping genomic lambda clones revealed that
      the gene spans about 30 kb and is made of 14 exons being 39 to 379 bp in length.
      The encoded protein is 550 amino acids long and is highly homologous to
      carboxylesterases of various mammalian species. The transcription start site was
      determined by 5'-RACE PCR. An additional 900 bp of DNA from the 5' flanking
      region of the gene was cloned and sequenced in order to elucidate the structure
      of the promoter. In this sequence several possible binding sites for
      transcription factors have been identified, but no TATA-box was present. When
      different parts of the putative promoter region were ligated in front of the
      luciferase gene and the constructs were transfected into CHO cells, the reporter
      gene was effectively transcribed, as demonstrated by the expression of enzyme
      activity.

PMID- 9003460
TI  - Compilation of ribosomal 5S ribonucleic acid nucleotide sequences: eukaryotic 5S
      rRNAs.
AB  - 5S Ribosomal RNA is the smallest RNA component of the ribosomes. Due to
      relatively simple isolation and sequencing procedures as well as a potential use
      of the sequence data in evolutionary analyses, the amount of known nucleotide
      sequences on both RNA and DNA levels was rapidly growing. In this paper we
      present the updated (March 1996) compilation of eukaryotic 5D rRNA and 5S rDNA
      sequences.

PMID- 9003462
TI  - Functional and sequence analysis of splicing defective nrdB mutants of
      bacteriophage T4 reveal new bases and a new sub-domain required for group I
      intron self-splicing.
AB  - The nrdB gene of bacteriophage T4 codes for the small subunit of ribonucleotide
      reductase and contains a 598 nuclelotide group 1 self splicing intron. In order
      to study the functional domains for self-splicing of this intron, 23 nrdB
      splicing defective intron mutants were analyzed for both sequence and functional
      changes. These mutants cluster towards the ends in regions of conserved
      structural elements of the intron. These 23 mutants have single base changes at
      14 different sites. Interestingly two of these sites that seemed to map within
      the intron are actually located on the flanking exon sequences on both sides of
      the intron. A high frequency (4/12) of the mutation sites are in bases not
      thought to be base-paired in the standard model of group I intron structure. The
      mutation sites in pairing regions P3, P7, P8, P9 and between P6[3'] and P7[5']
      are identical to changes found in the well studied td (encoding dTMP synthase)
      intron. However, five new mutation sites (S61, SL1, S29, SL11, SL196 and SL126)
      are unique to the nrdB intron and disrupt self-splicing. A mutation (S61) in the
      P7.1 pairing region is especially significant because no mutations have been
      found in this pairing, thus defining a new sub-domain essential for RNA splicing.
      Like the td intron, the mutation site in P9 of the nrdB intron is a hot spot for
      mutations, but unlike td, the nrdB intron does not show a mutational hot spot in
      the P6[5'] region. Our molecular dissection of the nrdB intron also supports the
      P9.0 and P10 pairings that have been postulated to help form a complex tertiary
      structure required to give the RNA sequence its catalytic activity: particularly
      3' splice site selection, cleavage and exon ligation.

PMID- 9003461
TI  - Analysis of carbon source-regulated gene expression by the upstream region of the
      Candida tropicalis malate synthase gene in Saccharomyces cerevisiae.
AB  - We investigated the regulation of expression of a gene encoding malate synthase
      (MS) of an n-alkane-utilizable yeast Candida tropicalis in the yeast
      Saccharomyces cerevisiae, where its expression is highly induced by acetate. By
      comparing levels of gene expression in cells grown on glucose, acetate, lactate,
      and oleic acid, we found that the increase in gene expression was due to a
      glucose repression-derepression mechanism. In order to obtain information
      concerning the regulation of the gene expression, a fusion gene which consists of
      the 5'-upstream region of MS-2 (UPR-MS-2) and the lacZ gene (encoding Escherichia
      coli beta-galactosidase), was introduced into S. cerevisiae, and beta
      galactosidase activities were measured with cells grown on glucose or acetate.
      Deletion analysis of UPR-MS-2 revealed that the region between -777 and -448
      (against the translation initiation codon) enhanced the level of gene expression
      in both glucose- and acetate-grown cells. In this region, sequences which
      resemble binding sites of Rap1p/Grf1p/Tufp, a global transcription activator,
      were found at seven locations and one was found for another pleiotropic activator
      Abf1p. The result also suggested the presence of multiple upstream repression
      sequences (URSs), which function specifically in glucose-grown cells, in the
      region between -368 and -126. In the repressing region, there were three tandem
      C(A/T)CTCCC sequences and also a putative binding site of Mig1p, a
      transcriptional repressor which mediates glucose repression of several other
      genes. When MIG1 gene of S. cerevisiae was disrupted, the expression of the UPR
      MS-2-lacZ gene in glucose-grown cells increased approx. 10-fold. Furthermore, the
      effect of deletion of a putative Mig1p binding site was abolished in the MIG1
      disrupted strain, suggesting Mig1p binds to this site and brings about glucose
      repression. When the SNF1 gene was disrupted, the high level gene expression
      observed in acetate-grown cells bearing UPR-MS-2 was abolished. This indicated
      that derepression of UPR-MS-2 -mediated gene expression was dependent on Snf1p,
      as is the case of genes encoding isocitrate lyase and gluconeogenic enzymes in S.
      cerevisiae.

PMID- 9003464
TI  - Hematopoietic augmentation by a beta-(1,4)-linked mannan.
AB  - CARN 750 (injectable acemannan) is a polydispersed beta-(1,4)-linked acetylated
      mannan isolated from the Aloe barbadensis plant. It has multiple therapeutic
      properties including activity in wound repair and as a biological agent for the
      treatment of neoplasia in animals as well as the ability to activate macrophages.
      We report herein that CARN 750 directly or indirectly has significant
      hematoaugmenting properties. We observed that the subcutaneous administration of
      CARN 750 significantly increases splenic and peripheral blood cellularity, as
      well as hematopoietic progenitors in the spleen and bone marrow as determined by
      the interleukin-3-responsive colony-forming unit culture assay and the high
      proliferative-potential colony-forming-cell (HPP-CFC) assay (a measure of
      primitive hematopoietic precursors) in myelosuppressed (7 Gy) C57BL/6 mice. The
      greatest hematopoietic effect was observed following sublethal irradiation in
      mice receiving 1 mg CARN 750/ animal, with less activity observed at higher or
      lower doses. Further, CARN 750, following daily injection, has activity equal to
      or greater than the injection of an optimal dose of granulocyte-colony
      stimulating factor (G-CSF) in myelosuppressed mice. In this comparison,
      significantly greater activity was observed in the splenic and peripheral blood
      cellularity, and in the frequency and absolute number of splenic HPP-CFC as
      compared to the mice receiving G-CSF at 3 micrograms/animal. CARN 750, when
      administered to myelosuppressed animals, decreased the frequency of lymphocytes
      with a concomitant significant increase in the frequency of polymorphonuclear
      leukocytes (PMN). However, owing to the increased cellularity, a significant
      increase in the absolute number of PMN, lymphocytes, monocytes and platelets was
      observed, suggesting activity on multiple cell lineages. The latter is the
      primary difference in activity as compared to G-CSF which has activity
      predominantly on PMN.

PMID- 9003463
TI  - Molecular cloning, upstream sequence and promoter studies of the human gene for
      the regulatory subunit RII alpha of cAMP-dependent protein kinase.
AB  - The gene for the regulatory subunit RII alpha of cAMP-dependent protein kinase is
      highly regulated during spermatogenesis and a strong signal from a distinct short
      mRNA form is observed postmeiotically during spermatid elongation. This report
      presents the isolation and characterization of the 5'-flanking region (1.2 kb)
      and exon 1 of the human RII alpha gene. S1 nuclease mapping and primer extension
      experiments revealed the presence of a major transcriptional start site located
      208 nucleotides upstream of start for translation. The 5'-flanking region of the
      RII alpha gene did not contain a TATA box and was highly G/C-rich. A basal
      promoter directing high levels of chloramphenicol acetyl transferase (CAT)
      activity was identified in the 5'-flanking sequence. Several potential binding
      sites for transcription factors were identified in this region, which may be
      responsible for the germ cell-specific regulation of this gene. We have
      previously reported that the human testis RII alpha cDNA contains a region (amino
      acids 45-75) with little or no homology to the corresponding rat skeletal muscle
      cDNA (Oyen, O., Myklebust, F., Scott, J.D., Cadd, G.G., McKnight, G.S., Hansson,
      V. and Jahnsen, T. (1990) Biol. Reprod. 43, 46-54). We examined whether this
      difference could arise due to organ-specific splice mechanisms or represented a
      species difference. We show that the low homology region of the human RII alpha
      cDNA resides entirely within exon 1, and does not originate from a tissue
      specific alternate splicing of this distinct region.

PMID- 9003465
TI  - Monocyte activation by an oral immunomodulator (bestatin) in lymphoma patients
      following autologous bone marrow transplantation.
AB  - Bestatin (ubenimex), an inhibitor of aminopeptidase, is an oral immunomodulator
      that binds to CD13 (aminopeptidase N) on macrophages/monocytes. To examine its
      immunomodulatory effect after high-dose therapy and autologous bone marrow
      transplantation (BMT), a dose-finding phase Ib trial was conducted with 30
      Hodgkin's disease and non-Hodgkin's lymphoma patients who received no drug
      (control), 10 and 30 mg (low dose), or 90 and 180 mg (high dose) of bestatin
      daily for 60 days following autologous BMT. Bestatin administration was initiated
      when the absolute neutrophil count was greater than 250/mm3 on 2 consecutive
      days. The serum neopterin levels, an indicator of monocyte/macrophage activation,
      increased in the high-dose group compared to the control group (not
      significantly) and the low-dose group (significantly). Similarly, the colony
      stimulating activity in the sera was significantly increased in the high-dose
      group compared to the control and low-dose groups. We also examined the
      expression of cell-surface markers on monocytes in these patients by fluorescent
      cytometry analysis. There was no significant difference either in the frequency
      or absolute number of monocytes (CD14+) among the three groups at any time.
      However, a significant increase in the frequency of CD16(FcgRIII)-positive
      monocytes (a marker of activation) was observed in the high-dose group compared
      to controls from day 14 to day 60 after the start of bestatin administration.
      Further, the frequency of HLA-DR+ monocytes (another marker of activation) was
      significantly increased in the high-dose group. These results indicate that
      bestatin at higher doses (90 and 180 mg daily), but not lower doses, activates
      macrophages/monocytes, as demonstrated by phenotypic marker (HLA-DR and CD16) up
      regulation, and this provides augmentation of neopterin and colony-stimulating
      activity in the serum of patients following autologous BMT.

PMID- 9003466
TI  - The expression of costimulatory molecules CD80 and CD86 in human carcinoma cell
      lines: its regulation by interferon gamma and interleukin-10.
AB  - The costimulatory signal through CD80 or CD86 to its counterreceptor CD28 or CTLA
      4 on T cells has been shown to play an important role in the induction of T-cell
      mediated immunity against tumors. In the present study, we examined the
      expression of CD80 and CD86 in the cell lines derived from human gastric,
      esophageal and colorectal carcinomas at the mRNA level, by means of a reverse
      transcriptase/polymerase chain reaction analysis and, for their surface
      expression, using a flow-cytometric analysis with monoclonal antibodies (mAb).
      The expression of mRNA for CD80 or CD86 was detected in all 18 cell lines tested,
      except for CD86 on one cell line. The cells from 13 (72%) or 12 (67%) of these
      cell lines expressed the surface CD80 or CD86 molecule, detected with the
      respective mAb. The surface expression of CD80 or CD86 was increased in four to
      five of the six cell lines tested after a culture with interferon gamma (IFN
      gamma). In addition, the up-regulation of CD80 or CD86 expression by IFN gamma
      was inhibited by interleukin-10 (IL-10). These results indicated that, in the
      cell lines derived from human gastrointestinal carcinoma, both the costimulatory
      molecules CD80 and CD86 were detectable in the majority of the cell lines
      examined at the mRNA and protein levels, and could be regulated with the cytokine
      IFN gamma or IL-10.

PMID- 9003467
TI  - Apoptosis in antibody-dependent monocyte-mediated cytotoxicity with monoclonal
      antibody 17-1A against human colorectal carcinoma cells: enhancement with
      interferon gamma.
AB  - Antibody-dependent cell-mediated cytotoxicity (ADCC) has been considered to be
      one of the main effector mechanisms by which unconjugated monoclonal antibody
      (mAb) 17-1A can exert an antitumor effect in vivo. Since the apoptotic pathway as
      well as the necrotic pathway have been shown to be utilized in various cytotoxic
      effector mechanism, we investigated the role of apoptosis in ADCC mediated by
      monocytes (ADMC) using mAb 17-1A as an antibody and the human colorectal
      carcinoma cell line, COLO205, as target cells in vitro. The implications of the
      apoptosis during ADMC was demonstrated by means of both a DNA fragmentation assay
      and a TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. Furthermore,
      interferon gamma (IFN gamma) was also found to enhance the induction of apoptosis
      significantly. The addition of superoxide dismutase did not reduce the level of
      the apoptosis, although superoxide anion (O2-) was observed to be produced.
      However, the release of tumor necrosis factor alpha (TNF alpha) was significantly
      enhanced during ADMC, while, in addition, apoptosis was significantly inhibited
      by the addition of anti-TNF alpha antibody. These findings indicated that
      apoptosis might be implicated in ADMC with mAb 17-1A, which was augmented by IFN
      gamma, while, in addition, TNF alpha may also be one of the major mediators of
      apoptosis.

PMID- 9003468
TI  - Heat-shock protein 72 cell-surface expression on human lung carcinoma cells in
      associated with an increased sensitivity to lysis mediated by adherent natural
      killer cells.
AB  - The cell-surface expression patterns of major histocompatibility complex (MHC)
      class I, class II and heat-shock protein 72 (HSP72) molecules were measured on
      human lung (LX-1) and mammary (MX-1) carcinoma cells. No major differences were
      found in the MHC cell-surface expression pattern of both cell lines. However,
      they differ significantly in their capacity to express HSP72 on their cell
      surface. Under physiological conditions LX-1 cells express HSP72 molecules on
      more than 90% of the cells, whereas MX-1 cells exhibit no significant HSP72 cell
      surface expression (less than 5%). These expression patterns remained stable in
      all further cell passages tested. The sensitivity to lysis mediated by an
      interleukin-2 (IL-2)-stimulated, adherent natural killer (NK) cell population
      could be correlated with the amount of cell-surface-expressed HSP72 molecules. By
      antibody-blocking studies, using HSP72-specific monoclonal antibody (mAb), a
      strong inhibition of lysis was only found with LX-1 cells but not with MX-1
      cells. In contrast to the cell-surface expression, the cytoplasmic amount of
      HSP72 in MX-1 cells was twice as high compared to LX-1 cells under physiological
      conditions. After nonlethal heat-shock the rate of induction and the total
      cytoplasmic amounts of HSP72 were comparable in both cell lines. The clonogenic
      cell viability of LX-1 cells after incubation at temperatures ranging from 41
      degrees C to 44 degrees C was significantly elevated compared to that of MX-1
      cells. In conclusion we state the following: (i) HSP72 cell-surface expression on
      human carcinoma cells is independent of the cytoplasmic amount of HSP72; (ii) the
      cell-surface expression of HSP72 is associated with an increased sensitivity of
      tumor cells to lysis mediated by an IL-2-stimulated, adherent NK cell population;
      (iii) thermoresistance is not related to the cytoplasmic HSP72 level but might be
      related to the amount of HSP72 expressed on the cell surface.

PMID- 9003470
TI  - Increased microvascular permeability induced by prolonged interleukin-2
      administration is attenuated by the oxygen-free-radical scavenger
      dimethylthiourea.
AB  - Effective use of interleukin (IL)-2 as an antineoplastic agent may be hindered by
      severe side-effects, in particular vascular leak syndrome, which leads to
      generalized, especially pulmonary, edema. The oxygen-free-radical scavenger
      dimethylthiourea (DMTU) was shown to attenuate IL-2-induced vascular leak
      syndrome in sheep receiving a single IL-2 injection. However, in the clinical
      setting multiple injections are necessary to gain a therapeutic effect. The
      present study tests whether DMTU attenuates IL-2-induced vascular leak syndrome
      following multiple IL-2 injections without affecting IL-2-induced cytotoxicity in
      peritoneal mononuclear cells. Mice were treated intraperitoneally with 1 x 10(5)
      units IL-2 three times daily for four consecutive days. DMTU (10 mg/0.5 ml) was
      administered to the study group once daily, prior to the first IL-2 injection.
      Comparing the wet/dry weight ratio of lungs, liver, and spleen showed that IL-2
      caused a significant (P < 0.05) wet/dry increase in all three organs. DMTU
      attenuated the wet/dry increase in the lungs (P < 0.05), in the spleen (P <
      0.05), and not at all in the liver. IL-2 induced a marked increase in peritoneal
      mononuclear cell counts, which was not attenuated by DMTU. The cytotoxic effect
      of IL-2-activated peritoneal mononuclear cells on target B16 cells was also
      unchanged in animals pretreated with DMTU. In conclusion, we have shown that DMTU
      ameliorates pulmonary permeability and vascular leak syndrome associated with
      multiple-dose IL-2 therapy, without eliciting an inhibitory effect on IL-2
      induced-cytotoxicity.

PMID- 9003469
TI  - Tumor reactivity of immune T cells in short-term culture.
AB  - The adoptive transfer of immune T cells is capable of mediating the regression of
      established neoplasms in a variety of animal tumor models. The antitumor activity
      is invariably proportional to the number of cells transferred, thus methods to
      expand immune cell number while maintaining therapeutic efficacy have been
      extensively investigated. Here we demonstrate that a short-term culture of immune
      T cells can amplify the T cell number and enhance the therapeutic reactivity
      against established pulmonary tumor, while maintaining immunological specificity.
      In contrast, the therapeutic reactivity of immune T cells against established
      subcutaneous tumor is diminished by short-term culture. While cultured immune T
      cells are not cytotoxic in a 4-h Cr-release assay, they do specifically secrete
      interferon gamma upon stimulation with tumor cells. T cells cultured after a
      single exposure to tumor are even more active against pulmonary tumor than T
      cells cultured from mice immunized repeatedly. This culture system can rapidly
      induce T cell proliferation and differentiation into mature effector cells, and
      the resulting cells demonstrate an enhanced ability to treat visceral metastases,
      but a decreased ability to treat subcutaneous tumor. Thus T cells cultured after
      a single exposure to tumor represent an ideal population of cells for use in
      human adoptive immunotherapy trials.

PMID- 9003471
TI  - Characterization of a high-affinity monoclonal antibody specific for CD44v6 as
      candidate for immunotherapy of squamous cell carcinomas.
AB  - Variant isoforms of CD44, a family of cell-surface glycoproteins generated by
      alternative splicing and post-translational modifications, are expressed in a
      variety of human tumors and play important roles in tumor progression and
      metastasis formation. The murine monoclonal IgG1 antibody VFF18, specific for an
      epitope encoded by human CD44 variant exon 6, binds with high affinity to the
      recombinant protein (Kd = 1.7 x 10(-10) M) as well as to tumor cell lines in
      vitro, and is suitable for immunohistochemical analysis of human tumors.
      Screening of more than 500 tumor samples of different histogenesis showed that
      VFF18 most strongly and uniformly reacts with squamous cell carcinomas (SCC).
      Detailed analysis of 185 SCC (head and neck, lung, skin) confirmed reactivity of
      the antibody with 99% of the samples, with intense and homogeneous staining of
      the tumor cells in the majority of cases, whereas reactivity of VFF18 with normal
      tissues is limited to certain epithelia and activated lymphocytes. When
      radiolabelled VFF18 was administered to nude mice bearing human epidermoid
      carcinoma (A-431) xenograft, fast and selective tumor uptake of the
      radioimmunoconjugate with a maximum of 18% of the injected dose per gram of
      tissue was observed. Taken together, these data suggest that mAb VFF18 is a
      promising targeting vehicle for radioimmunotherapy of squamous cell carcinomas in
      humans.

PMID- 9003472
TI  - Once more unto the breach. Inaugural meeting of the British Society for
      Immunology Tumour Immunology Affinity Group.

PMID- 9003473
TI  - Clinical implications of serum levels of soluble CD23 and tumor necrosis factor
      alpha in low-grade non-Hodgkin's lymphoma.
AB  - In the last few years the research for new biological features in low-grade non
      Hodgkin's lymphoma has provided important results. Several biological parameters
      are under evaluation and, in particular, cytokines and soluble receptors levels
      are showing their importance as prognostic parameters. In the present study,
      serum levels of tumor necrosis factor alpha (TNF-alpha) and soluble CD23 (sCD23)
      were measured at the time of diagnosis and after induction polychemotherapy in 40
      patients with newly diagnosed low-grade non-Hodgkin's lymphoma (LG-NHL). The
      treatments were CIOP (cyclophosphamide, idarubicin, vincristine, prednisone)
      regimen for 28 patients and FMP (fludarabine, mitoxantrone, prednisone) scheme
      for 12 patients. Pretreatment levels of TNF-alpha were highly elevated in patiets
      with LG-NHL compared with healthy controls (p = 0.005) and were significantly
      correlated with the Ann Arbor stage (p = 0.001). sCD23 was detected in 35
      patients at diagnosis and were markedly increased in LG-NHL patients when
      compared to healthy controls (p = 0.005); patients with advanced stage presented
      higher values than those with early stage disease (p = 0.002). All the complete
      responders (20/40, 50%) showed a decrease of TNF-alpha and sCD23 levels. By
      contrast, the combination of high levels of TNF-alpha and sCD23 correspond to a
      group of non-responders. Our results suggest that TNF-alpha and sCD23 are
      specific prognostic parameters for LG-NHL, and that they could be used as tumor
      markers within a potential biological prognostic index.

PMID- 9003474
TI  - Early diagnosis of low grade malignant lymphoma and chronic lymphocytic
      leukaemia. Verification of morphologically suspected malignancy in blood
      lymphocytes by flow cytometry.
AB  - According to international recommendations, the diagnosis of chronic lymphocytic
      leukaemia (CLL) is made on the grounds of persistent peripheral lymphocytosis or
      lymphocytic infiltration of the bone marrow. The appearance of morphologically
      atypical lymphocytes in low-grade malignant lymphoma (NHL) or CLL is easily
      overlooked, and is generally not regarded as a diagnostic criterion. We report 12
      cases of CLL/NHL who were detected only by morphological screening of routine
      peripheral blood smears (83,400 blood smears). The diagnosis of CLL/NHL was not
      suggested by the patients' history, physical or other laboratory findings, and
      had not been contemplated by the physician in charge. Monoclonality of peripheral
      lymphocytes was confirmed by immunophenotyping and Southern blotting. The
      lymphoma was classified histologically according to the International Working
      Formulation (bone marrow biopsy). A monoclonal lymphatic population was not found
      by immunophenotyping in the blood of 11 patients whose lymphocytes were
      morphologically classified as activated-abnormal. However, 3 patients suspected
      to have NHL/CLL on morphological screening of blood smears had to be classified
      as benign after immunophenotyping. We conclude that morphological screening of
      routine blood smears is an inexpensive and easy additional screening method for
      CLL and low grade malignant NHL.

PMID- 9003475
TI  - Adhesive interactions between tumour cells and bone marrow stromal elements in
      human multiple myeloma.
AB  - Long-term bone marrow cultures (LTBMC) were established from marrow samples
      obtained from 6 myeloma patients and 5 healthy donors and were examined by in
      situ immunogold-silver staining. During the culture period, the established
      stroma in myeloma LTBMC revealed a lower level of confluency compared to the
      normal LTBMC. In addition, an increasing proportion of macrophages and
      osteoclasts was observed in the myeloma stroma throughout the culture period.
      Moreover, plasma cells were detectable by wk 8, mostly organized in small
      clusters. They strongly expressed VLA-4 (6/6), H-CAM (6/6), ICAM-1 (6/6) and N
      CAM (3/6). In most cases, a weak expression of the other members of beta 1
      integrins was observed. The expression of beta 2-integrins was always absent.
      Stromal fibroblasts were found to be weakly positive for VLA-2, VLA-3 and VLA-5
      and showed strong expression of VCAM-1, H-CAM and ICAM-1. N-CAM expression could
      not be detected. By comparing the adhesion molecule profile of the stromal cells
      in myeloma cultures with normal bone marrow (BM) cultures, no particular defects
      could be observed. The stroma displayed most of the potential ligands which could
      interact with adhesion molecules detected on the myeloma cells. Among these
      ligands we could find fibronectin and VCAM-1 for VLA-4, collagen I for VLA-2 and
      VLA-3 and laminin for VLA-2, 3 and 6. Four myeloma cell lines, i.e. OPM-1, U266,
      RPMI 8226 and JJN3, with a representative phenotype, were used to study the
      adhesive interactions of myeloma cells with the BM microenvironment. All the
      myeloma cell lines bound strongly to the marrow cell layers and also showed a
      high binding to purified fibronectin (FN). However, the adhesion of the cell
      lines to intact stroma could not be significantly inhibited by anti-FN receptors
      antibodies. Nor could it be prevented when the latter were combined with anti-H
      CAM, V-CAM and ICAM-1 antibodies, as tested in the JJN3 cell line. This implies
      that other unknown mechanisms contribute to the myeloma cell binding.

PMID- 9003476
TI  - Serum erythropoietin levels in patients with sepsis and septic shock.
AB  - The role of the immune system in the control of the production of erythropoietin
      is still poorly understood. Herein, the levels of circulating immunoreactive
      erythropoietin, tumour necrosis factor alpha, interleukin-1 beta and interleukin
      6 were determined in 10 septic patients for up to 4 d following the admission to
      an internal intensive care unit. The data show that the production of
      erythropoietin was not suppressed despite an increase in the levels of
      proinflammatory cytokines. Circulating erythropoietin and interleukin-6 greatly
      increased in the 6 nonsurviving patients. The pattern of the serum erythropoietin
      level in the nonsurvivors resembled that of acute phase proteins and was
      independent of the blood haemoglobin concentration. Similar to interleukin 6,
      abnormally high serum erythropoietin levels appear to be a negative prognostic
      indicator in patients suffering from septic shock.

PMID- 9003477
TI  - Increased serum levels of macrophage colony-stimulating factor (M-CSF) in alpha-
      and beta-thalassaemia syndromes: correlation with anaemia and monocyte
      activation.
AB  - Serum levels of M-CSF were determined by an ELISA method in 29 and 34 patients
      with HbH disease (alpha 1/alpha 2 or alpha 2/HbCS) or beta zero-thal/HbE,
      respectively, in 28 haematologically normal subjects and in five patients with
      anaemia due to iron deficiency or myelodysplasia. In HbH disease and beta zero
      thal/HbE, M-CSF concentrations were significantly higher than those in the normal
      subjects [986 +/- 138 and 1385 +/- 133, respectively, vs. 500 +/- 33 pg/ml (mean
      +/- SEM); p < 0.01, and p < 0.001, respectively]. By contrast, in patients with
      anaemia due to iron deficiency, M-CSF levels were within the normal range. In HbH
      disease and in beta zero-thal/HbE, M-CSF levels correlated inversely with mean
      basal Hb values (r = -0.39, p = 0.05 and r = -0.60, p < 0.001, respectively). In
      addition, in some of the HbH and beta zero-thal/HbE patients, monocyte ADCC
      activities towards red cells were tested and found to be approximately twice as
      high as those in normal controls [38.3 +/- 5.7 and 30.7 +/- 4.6 vs. 17.8 +/- 1.8%
      specific lysis (mean +/- SEM), respectively; p < 0.01 and p < 0.02,
      respectively]. When thalassaemic patients and normal controls were considered
      together there was a significant correlation between M-CSF levels and monocyte
      ADCC activities (r = 0.51, p < 0.02). The results suggest that in HbH disease and
      in beta zero-thal/HbE, raised serum M-CSF contributes to the anaemia by enhancing
      the effector function of mononuclear phagocytes towards red cells.

PMID- 9003478
TI  - Assessment of bone involvement in patients with multiple myeloma using bone
      densitometry.
AB  - To evaluate the use of dual energy X-ray absorptiometry (DXA) in multiple myeloma
      (MM) we performed a prospective study of 34 patients with newly diagnosed MM.
      Most patients had advanced disease and all but two patients had osteolytic bone
      destructions and/or pathological fractures. Bone mineral content (BMC) and bone
      mineral density (BMD) of the lumbar spine (L1-L4) and hip were measured using a
      Hologic QDR-1000 scanner. Collapsed vertebrae were not excluded from analysis.
      Data from 289 healthy Danish volunteers aged 21-79 yr were used for calculation
      of Z-scores. Lumbar spine BMC (Z-score -0.46 +/- 0.23, p = 0.05) and lumbar spine
      BMD (Z-score -0.56 +/- 0.23, p = 0.02) were significantly reduced in MM patients,
      whereas no reduction was seen in hip BMC or BMD. Collapsed vertebrae had marked
      reduced BMD (Z-score -1.34 +/- 0.22, p < 0.001), as had non-fractured vertebrae
      in the same individuals (Z-score -1.42 +/- 0.25, p < 0.001). Lumbar spine BMD
      correlated with radiologically assessed bone morbidity (r -0.37, p = 0.03) and
      stronger with the incidence of vertebral fractures (r -0.64, p < 0.001). Thus,
      osteopenia of the back is common in multiple myeloma and correlates with an
      increased incidence of fractures. DXA may identify subjects with increased risk
      of vertebral fractures for more intensive chemotherapeutic or anti-resorptive
      treatment.

PMID- 9003479
TI  - CHOP vs. ProMACE-CytaBOM in the treatment of aggressive non-Hodgkin's lymphomas:
      long-term results of a multicenter randomized trial.(PETHEMA: Spanish Cooperative
      Group for the Study of Hematological Malignancies Treatment, Spanish Society of
      Hematology).
AB  - From May 1985 to May 1989, 175 patients with previously untreated aggressive non
      Hodgkin's lymphoma were randomized to receive CHOP or ProMACE-CytaBOM.
      Eligibility criteria included follicular large-cell diffuse small cleaved-cell,
      diffuse mixed, diffuse large-cell and immunoblastic lymphoma with an Ann Arbor
      stage II, III or IV. One hundred and forty-eight patients were evaluable. There
      were no significant differences between the 2 treatments in response rate (83.5%
      [57.5% CR] for CHOP vs. 88% [62% CR] for ProMACE-CytaBOM), time to treatment
      failure (29% vs. 31% at 5 yr), or overall survival (42% in both groups at 5 yr).
      Furthermore, there were no significant differences between the 2 regimens when
      response rates and outcome were analyzed for different prognostic subgroups.
      Toxicity was not significantly different between the 2 regimens, although only 1
      patient died as result of treatment-related toxicity in the CHOP arm compared to
      6 patient in the ProMACE-CytaBOM group (p = 0.126). In conclusion, in this study
      ProMACE-CytaBOM has not proved to be superior to CHOP in aggressive lymphomas.
      This trial gives support to the notion that CHOP still is the standard
      chemotherapy for aggressive lymphomas, and that new treatment approaches for
      these lymphomas should be compared to CHOP.

PMID- 9003480
TI  - Changes in serum erythropoietin and the reticulocyte count during chemotherapy
      for leukemias.
AB  - We serially determined serum erythropoietin (Epo) and the reticulocyte count in
      patients with various types of leukemia during chemotherapy. Serum Epo increased
      soon after the initiation of chemotherapy and decreased after the termination of
      therapy irrespective of the types of leukemia or treatment regimen. However, it
      did not stay at low level but fluctuated. The reticulocyte count, on the other
      hand, showed a transient rise while serum Epo level descended. The value of serum
      Epo when increased was higher than the value expected from hemoglobin
      concentration; this finding was similar to that in aplastic anemia. These results
      suggest that myelosuppression is a major factor for the increase in serum Epo
      level during leukemia chemotherapy.

PMID- 9003481
TI  - Molecular heterogeneity of beta-thalassaemia in a Spanish population from the
      area centre of Spain.

PMID- 9003482
TI  - Retinoic acid syndrome (RAS) in an aplasic patient with secondary acute
      promyelocytic leukemia (APL)

PMID- 9003484
TI  - An asymptomatic germline missense base substitution in the hypoxanthine
      phosphoribosyltransferase (HPRT) gene that reduces the amount of enzyme in
      humans.
AB  - A 40-year-old normouricemic (5.5 mg/dl) male showed 46% hemolysate and 37%
      lymphoblast hypoxanthine phosphoribosyltransferase (HPRT) activities but was
      otherwise completely free of symptoms. His genomic DNA and cDNA had a missense
      base substitution (CAT-to-CGT in codon 60) leading to the amino-acid substitution
      His-to-Arg. Western blot analysis revealed that the amount of HPRT protein in
      lymphoblasts from this individual was 25%-50% of normal cells, suggesting that
      the decrease in the amount of enzyme protein was responsible for the partial
      deficiency. This provides the first clear evidence that a genomic missense
      mutation at the HPRT locus leads to a decrease in the amount of the enzyme
      protein but that otherwise it has no evident adverse effects in the hemizygote
      (asymptomatic mutation).

PMID- 9003485
TI  - Refined molecular characterization of the breakpoints in small inv dup(15)
      chromosomes.
AB  - Inv dup(15) is the most common supernumerary marker chromosome in humans. To
      investigate the mechanism responsible for this frequent chromosome rearrangement,
      we characterized the breakpoints in 18 individuals with small inv dup(15)
      chromosomes [i.e., negative for the Prader-Willi (PWS)/Angelman syndrome (AS)
      critical region]. Since two proximal breakpoint regions ("hotspots") for PWS/AS
      deletions have been previously identified with the most proximal 15q markers
      D15S541/S542 and S543, we hypothesized that formation of the small inv dup(15)
      chromosomes may involve one or both of these breakpoint hotspots. By analysis
      with S542, both breakpoint regions were found to be involved in approximately
      equal frequencies. In ten cases, the inv dup(15) was negative for S542 (Class I),
      indicating the breakpoint is between the centromere and the most proximal marker
      on chromosome 15. For the other eight cases, S542 was positive by fluorescence in
      situ hybridization (5/5) and/or microsatellite analysis (7/7), but S543 was
      negative (Class II). These two breakpoint regions appear to be the same as the
      two proximal breakpoints reported in the common PWS/AS deletions. To initiate
      cloning and sequencing of the Class II breakpoint, the gap in the yeast
      artificial chromosome (YAC) contig between S541/S542 and S543 was filled by
      screening the CEPH YAC and mega-YAC libraries. YACs 705C2 and 368H3 were found to
      bridge this gap, and therefore contain the more distal breakpoint region. The
      finding of consistent breakpoints in small inv dup(15), like that found in PWS/AS
      deletions, provides strong evidence for hotspots for chromosome breakage in this
      region. In addition, our results show that two extra copies (tetrasomy) of the
      region from 15cen to the euchromatic region containing S542 are present in
      individuals with Class II breakpoints. Since most individuals carrying a small
      inv dup(15) are phenotypically normal, the euchromatin region included in the
      small inv dup(15) chromosomes does not appear to contain genes with clinically
      significant dosage effects.

PMID- 9003483
TI  - Microsatellite variation and the differentiation of modern humans.
AB  - This study presents an analysis of 20 tetranucleotide microsatellites in 16
      worldwide human populations representing the major geographic groups. Global Fst
      values for the 20 microsatellites are indicators of their relative validity as
      tools in human population genetics. Four different measures of genetic distance
      (Fst, DSW, delta mu 2 and Rst) have been tested and compared with each other.
      Neighbor-joining trees have been constructed for all the measures of genetic
      distance and populations. Measures of genetic distance such as Fst, which does
      not consider different mutational relationships among alleles and has a known
      relationship to differentiation by drift, and to some extent DSW, reflect what is
      known of human evolution, while mutation-based distances such as Rst and delta mu
      2 give very different results from those recognized from other sources (genetic
      or archaeological). When the genetic relationship between human populations is
      analyzed through allelic frequencies for microsatellites, the choice of distance
      may be a key issue in the picture obtained of genetic relationships between human
      populations. The results of the present study suggest that genetic drift played
      the main role in generating the present distributions of microsatellite alleles
      and their variation among human populations; the role of mutation must have been
      less important owing to the time constraint imposed by the small timescale in
      which most human differentiation has occurred. Moreover, the results support the
      theory of a recent origin of modern humans, although the existence of strong
      bottlenecks in the origin of the various human groups seems unlikely.

PMID- 9003486
TI  - Molecular evidence for human alpha 2-HS glycoprotein (AHSG) polymorphism.
AB  - Alpha 2-HS glycoprotein (AHSG) is a human plasma glycoprotein that exhibits
      genetic polymorphism on isoelectric focusing (IEF). To identify the origin of two
      common alleles, AHSG*1 and *2, we examined nucleotide exchanges in the gene. AHSG
      cDNA was obtained by RT-PCR from poly(A) RNA of seven liver tissue samples and
      subcloned into a plasmid vector. After sequencing, we found six single nucleotide
      differences in comparison with the originally reported sequence. In particular,
      the nucleotide substitutions of C to T at amino acid position 230 and C to G at
      position 238 were common among the samples exhibiting phenotype 2-1 or 2. Since
      these substitutions might give rise to a NlaIII site and a SacI site,
      respectively, for the potential AHSG*2, we analyzed these substitutions by PCR
      RFLP using genomic DNA of 68 individuals. The result was consistent with the IEF
      analysis of the corresponding serum, indicating that AHSG*1 was characterized by
      ACG (Thr) at position 230 in exon 6 and ACC (Thr) at position 238 in exon 7, and
      that AHSG*2 was characterized by ATG (Met) at position 230 and AGC (Ser) at
      position 238.

PMID- 9003487
TI  - Evidence for an association between markers on chromosome 19q and non-syndromic
      cleft lip with or without cleft palate in two groups of multiplex families.
AB  - It has been reported that BCL3 on chromosome 19q, or a nearby gene, may play a
      role in the etiology of non-syndromic cleft lip with or without cleft palate
      (NSCL/P) in some families. We tested 30 USA and 11 Mexican multiplex NSCL/P
      families for four markers on chromosome 19q: D19S178, APOC2/AC1, APOC2/007, and
      BCL3. While likelihood-based linkage analysis failed to show significant evidence
      of linkage, the transmission disequilibrium test indicated highly significant
      deviation from independent assortment of allele 3 at the BCL3 marker in both data
      sets (USA:P = 0.001; Mexican: P = 0.018; both combined: P < 0.001) and for allele
      13 of the D19S178 marker in the Mexican data set (P = 0.004). These results
      support an association, possibly due to linkage disequilibrium, between
      chromosome 19 markers and a putative NSCL/P locus.

PMID- 9003488
TI  - Microsatellite polymorphism of the alpha 1-antichymotrypsin gene locus associated
      with sporadic Alzheimer's disease.
AB  - A variant of the apolipoprotein E gene, APOE*4, is associated with both sporadic
      Alzheimer's disease (AD) and a subset of familial AD and this association is
      stronger with early as opposed to late onset AD. Both APOE*4 and alpha 1
      antichymotrypsin (ACT) will accelerate the rate of amyloid filament formation and
      are major constituents of the plaques associated with AD. We now show that a
      dinucleotide microsatellite allele in the 5'-flanking sequence of the ACT gene,
      designated A10, in association with APOE*4 significantly increases the risk of
      developing sporadic AD, which accounts for the majority of AD cases.

PMID- 9003489
TI  - Localization of the human HuR gene to chromosome 19p13.2.
AB  - The HuR gene encodes a specific RNA binding protein that is a member of the human
      Elav-like gene family. This family of proteins, which includes HuD, HuC and Hel
      N1, is involved in cellular differentiation. Alterations of HuD and Hel-N1
      structure are associated with small cell lung tumors and medulloblastomas. To
      investigate a possible linkage of the HuR gene to malignancy, the locus of the
      gene was mapped on human metaphase chromosomes. Analysis of the fluorescence
      signals on banded chromosomes showed that the HuR gene is localized to human
      chromosome 19p13.2 the cell cycle and proliferation (Levine et al. 1993; Gao et
      al. 1994; Liu et al. 1995; Chung et al. 1996). HuD and Hel-N1 are aberrantly
      spliced in human tumors yielding isoforms that are incapable of inducing
      differentiation (Gao et al. 1994; Antic et al. 1996). Thus it is feasible that
      rearrangements of the HuR gene may occur in other human tumors. In order to
      investigate this possibility we have mapped the HuR gene using fluorescence in
      situ hybridization (FISH).

PMID- 9003490
TI  - Amplified product length polymorphism (APLP): a novel strategy for genotyping the
      ABO blood group.
AB  - We present a simple rapid reproducible polymerase chain reaction based technique,
      termed amplified product length polymorphism (APLP), as a new strategy for primer
      design for ABO genotyping. The method involves the use of primers differing in
      length and permits the identification of the major ABO genotypes (A1, A2, B, OA,
      OG, and O2) according to the molecular size of the allele-specific amplified
      products. Ten different primers designed to analyze the variations in nucleotide
      positions 261, 297, 796, 802, and 1059-1061 of cDNA are mixed in one reaction,
      and the amplified products are resolved on a polyacrylamide gel. Of eight PCR
      fragments (132 bp, 120 bp, 108 bp, 98 bp, 88 bp, 80 bp, 72 bp, and 64 bp), two to
      five are amplified in the reaction according to ABO genotypes. The new technique
      has been successfully applied to the genotyping of 221 peripheral blood samples
      from Japanese and Germans whose ABO phenotypes had previously been determined; a
      novel A allele (AG) was found in Japanese individuals.

PMID- 9003491
TI  - Allelic variants of human calcitonin receptor in the Japanese population.
AB  - Evidence from cDNA cloning has shown that calcitonin receptors (CTRs) have seven
      potential transmembrane domains. In this study, structural analysis of CTRs from
      ten cultured human tumor cell lines and 117 human blood samples demonstrated
      allelic variants at the 1377th nucleotide in intracellular domain 4, expressing
      either proline or leucine as the 463rd amino acid. It was found that the variant
      with proline at this site was the more prevalent type of CTR among the Japanese
      population.

PMID- 9003492
TI  - Analysis of chromosomal equipment in spermatozoa of a 46,XY/47,XY/+8 male by
      means of multicolour fluorescent in situ hybridization: confirmation of a
      mosaicism and evaluation of risk for offspring.
AB  - Trisomy 8 is generally associated with chromosomal mosaicism and occurs de novo,
      with relatively well-defined clinical manifestations, ranging from minimal
      effects to severe malformations. Mosaicism is often difficult to ascertain and
      the confirmation of diagnosis requires several chromosomal investigations on a
      variety of tissues. We present a case of mosaic trisomy 8 fortuitously found in a
      healthy 30-year-old man during a cytogenetic investigation for several
      spontaneous abortions: 8% of the lymphocyte metaphases showed a 47,XY,+8
      karyotype. Fluorescent in situ hybridization (FISH) with the probes pJM.128 and
      L1.84 was performed on decondensed interphase spermatozoa. Of the 25000 analysed
      cells, 398 spermatozoa (1.59%) exhibited a hybridization pattern compatible with
      a chromosome 8 disomy; the frequency was higher than in either sperm control
      populations (0.17% and 0.21%). This result is in agreement with the existence of
      trisomy 8 mosaicism in the gonads and germ cells. FISH on decondensed interphase
      spermatozoa spreads is thus an easy non-invasive procedure that can be used to
      complement mosaicism diagnosis in tissue other than blood. Moreover, FISH
      provides interesting data for characterizing the risk for offspring.

PMID- 9003493
TI  - Latent chromosomal instability in cancer patients.
AB  - There is increasing evidence that, similar to what is found with other genetic
      disorders, genomic instability is one of the most general features of cancer.
      Different forms of manifestation including latent instability have been
      suggested. To recognize latent chromosomal instability we treated lymphocyte
      cultures of cancer patients and healthy persons with caffeine, two different
      doses of bleomycin, and a combination of bleomycin and caffeine. The preliminary
      results demonstrate that, although the rate of spontaneous chromosomal
      aberrations is similar in both investigated groups, the lymphocytes of cancer
      patients display an increased susceptibility to treatment with bleomycin and
      caffeine. In distinguishing between healthy individuals and those with
      malignancy, treatment with 30 micrograms/ml bleomycin appears to be most
      important. Values of chromosomal change above one break per cell, more than 45%
      cells with chromosomal alterations, and more that two cells with chromosomal
      rearrangements are suggestive of malignancy. These findings imply that treatment
      of lymphocyte cultures with bleomycin and caffeine could be a useful assay for
      monitoring chromosomal instability, and thus detecting a predisposition to
      malignant disease. In this respect further investigations on a greater amount of
      material should be performed.

PMID- 9003494
TI  - Possible control of dopamine beta-hydroxylase via a codominant mechanism
      associated with the polymorphic (GT)n repeat at its gene locus in healthy
      individuals.
AB  - Six allelic fragments were typed by a PCR-based process with a pair of primers
      specific for a sequence containing the polymorphic (GT)n repeat at the human
      dopamine beta-hydroxylase (DBH) locus in 125 unrelated healthy individuals. Their
      frequencies among these individuals were 0.012 (A1), 0.08 (A2), 0.344 (A3), 0.548
      (A4), 0.004 (A5) and 0.012 (A6); the two major alleles, A3 and A4, made up nearly
      90% of the alleles. These individuals were divided into four groups according to
      the genotype they possessed, i.e. A3/A3, A4/A4, A3/A4 and others (mixed group).
      Kruskal-Wallis analysis revealed a significant difference in serum DBH activity
      among these four genetic groups (H = 32.7, P < 0.0001). The homozygotic
      genotypes, A3/A3 and A4/A4, were associated with low and high DBH activity,
      respectively, and the heterozygotic genotype, A3/A4, seemed to play a role in
      keeping the DBH activity at a moderate level. The present work suggests that the
      human DBH is likely to be controlled via a codominant mechanism associated with
      the dinucleotide repeat polymorphism at its gene locus.

PMID- 9003495
TI  - Investigation of deletions at 7q11.23 in 44 patients referred for Williams-Beuren
      syndrome, using FISH and four DNA polymorphisms.
AB  - Williams syndrome (WS) is associated with a submicroscopic deletion of the
      elastin gene (ELN) at 7q11.23. The deletion encompasses closely linked DNA
      markers. We have investigated 44 patients referred for possible WS using
      fluorescence in situ hybridization (FISH) analysis with a P1 clone containing an
      insert from the ELN, as well as performing genotype analysis of patients and
      parents with four DNA polymorphisms. Twenty-four patients were found to have
      deletions, 19 of whom were found clinically to have typical WS. The facial
      features were especially characteristic. None of the patients without detectable
      deletions was reported to have typical WS features, although one had
      supravalvular aortic stenosis, hypercalcemia, and mental retardation. No evidence
      was found in this material for variability of the size of the deletion. Our study
      supports the usefulness of analysis of ELN deletion in WS patients, both for
      confirmation of diagnosis and for genetic counselling.

PMID- 9003496
TI  - PCR-based detection of mosaicism in Turner syndrome patients.
AB  - To study the possible role of cryptic mosaicism in phenotypical variations of
      45,X Turner syndrome, we analyzed low-level mosaicism by methods based on the
      polymerase chain reaction. For the detection of Y-chromosome-derived fragments,
      we used three Y-specific primer pairs representing the centromere, Yp11.3, and
      Yq12. None of the 18 patients with 45,X had Y-derived chromosomes. For the
      detection of X chromosome mosaicism, we employed a novel modified HUMARA (human
      androgen receptor) assay, which proved to be a sensitive method with a detection
      limit as low as 1 in 960 cells. Using this assay, we detected low frequency
      cryptic X chromosome mosaicism in 2 of 18 cytogenetically 45,X patients.

PMID- 9003498
TI  - Prevalence of delta F508 cystic fibrosis carriers in The Netherlands: logistic
      regression on sex, age, region of residence and number of offspring.
AB  - An average cystic fibrosis (CF) carrier frequency of 1 in 25 in Europe is cited
      in numerous reports, although a great variability in estimated prevalences has
      been found in different European populations. The estimates of these frequencies
      were based on numbers of CF patients before identification of the gene in 1989.
      Here we report the results of a study to determine the carrier frequency of the
      delta F508 mutation in The Netherlands by analyzing mouthwashes and matched blood
      samples from 11654 blood donors all over the country. We analyzed possible
      relationships between a number of theoretically explanatory variables and the
      delta F508 carrier frequency by means of univariate and multivariate logistic
      regression. These variables were: distance of the blood banks from the
      northeastern part of the country (distance); whether the blood donors knew that
      we were looking for a CF mutation; sex and age of the donor; and number of
      children of the donor (family size). We detected a delta F508 carrier frequency
      of 1 in 42 (95% CI 1/37-1/47) in The Netherlands. If we assume that the relative
      frequency of the delta F508 mutation among carriers and patients is comparable in
      The Netherlands, this gives an estimated overall CF carrier frequency of 1 in 32
      (95% CI 1/28-1/36), significantly less than 1 in 25. The univariate logistic
      regression analysis of the effects of the explanatory variables on the carrier
      frequency revealed no significant relationships, except for an increase in
      carrier frequency with increasing distance from the northeastern region. In the
      multivariate analysis with all five independent variables, distance, age and
      family size were significantly related to the carrier frequency, but sex and CF
      information were not. There was a significant interaction between age and family
      size. In our final model, distance, age and family size were positively related
      to the carrier frequency, while the interaction of age with family size showed a
      negative relation. These results confirm that there is a gradient in gene
      frequency with low frequencies in the northeastern part of the country and high
      frequencies in the southern part. They also suggest a relation of age and family
      size with carrier frequency. This relation, however, is too complex to be
      explained by heterozygote advantage.

PMID- 9003497
TI  - Genetic polymorphisms of the renin-angiotensin system and angiographic extent and
      severity of coronary artery disease: the CORGENE study.
AB  - Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated
      with coronary artery disease (CAD) but no relation between these polymorphisms
      and coronary atherosclerosis has yet been systematically evaluated. The CORGENE
      study is a cross-sectional study involving 463 Caucasians who underwent
      standardized coronary angiography for established or suspected CAD [156 patients
      with a previous myocardial infarction (MI), 307 without MI]. Four angiographic
      scores assessing the extent and severity of the coronary lesions were obtained
      from a double visual analysis of each angiogram, arbitration being achieved by a
      quantitative measurement. Three different genotypes were analyzed: the
      angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism, the
      Met to Thr change at position 235 of the angiotensinogen gene (AGT M235T) and the
      A to C transition at position 1166 of the angiotensin II type-1 receptor gene
      (AT1R A1166C). No significant association was observed between these
      polymorphisms and the clinical characteristics of MI and non-MI subjects. While
      most classical risk factors were positively correlated with the angiographic
      scores, no significant relationship could be established with the three genotypes
      (r ranging from -0.08 to 0.05). Only one significant correlation was observed:
      between the presence of the AGT 235T allele and the extent of the coronary
      lesions (r = -0.19, P = 0.04) in patients with low-risk status. These overall
      results are not in favor of a role of these RAS genetic polymorphisms in the
      development of coronary atherosclerosis.

PMID- 9003499
TI  - Refined localization of the pyruvate dehydrogenase E1 alpha gene (PDHA1) by
      linkage analysis.
AB  - Pyruvate dehydrogenase (PDH) E1 alpha is a key component in the PDH complex which
      catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA. Defects in the
      gene coding for PDH E1 alpha (PDHA1) are associated with a variety of clinical
      symptoms, often of a severe character. In the present study, the segregation of
      three polymorphic CA repeats located in PDHA1 was followed in the 40 CEPH
      reference pedigrees. Using these data, multipoint linkage analysis was carried
      out, refining the genetic location of PDHA1. The 16-point map presented locates
      PDHA1 in an approximately 3-cM interval between DXS999 and DXS365 with odds of
      more than 1000:1. From known physical localizations of the flanking marker loci,
      PDHA1 could be regionally assigned to Xp22.1-p22.2. The information provided
      should be of value in clinical settings.

PMID- 9003500
TI  - X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a
      missense mutation (N4401) in the DAX-1 gene; implication for genetic counselling
      and carrier diagnosis.
AB  - X-linked congenital adrenal hypoplasia (AHC) is a developmental disorder of the
      human adrenal gland that results in profound hormonal deficiencies, which are
      lethal if untreated. Hypogonadotropic hypogonadism (HHG) is frequently associated
      with this disorder. The gene (DAX-1) responsible for the disease has recently
      been isolated. It encodes a protein with large similarity to members of the
      nuclear hormone receptor superfamily. Several different mutations in this gene
      have been found in patients suffering from AHC. We have identified a missense
      mutation (N440I) in three patients with AHC and HHG, all belonging to a large
      Greenlandic family. A total of 42 individuals has been tested for this mutation.
      We have diagnosed 10 women as carriers, and have excluded 22 women with a 25-50%
      risk from being carriers, emphasizing the rapid impact of molecular genetic
      techniques.

PMID- 9003501
TI  - Mutational and functional analysis of the neurofibromatosis type 1 (NF1) gene.
AB  - Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant
      disorders. It is caused by mutations in the NF1 gene which comprises 60 exons and
      is located on chromosome 17q. The NF1 gene product, neurofibromin, displays
      partial homology to GTPase-activating protein (GAP). The GAP-related domain
      (GRD), encoded by exons 20-27a, is the only region of neurofibromin to which a
      biological function has been ascribed. A total of 320 unrelated NF1 patients were
      screened for mutations in the GRD-encoding region of the NF1 gene. Sixteen
      different lesions in the NF1 GRD region were identified in a total of 20
      patients. Of these lesions, 14 are novel and together comprise three missense,
      two nonsense and three splice site mutations plus six deletions of between 1 and
      4 bp. The effect of one of the missense mutations (R1391S) was studied by in
      vitro expression of a site-directed mutant and GAP activity assay. The mutant
      protein, R1391S, was found to be some 300-fold less active than wild-type NF1
      GRD. The mutations reported in this study therefore provide further material for
      the functional analysis of neurofibromin as well as an insight into the
      mutational spectrum of the NF1 GRD.

PMID- 9003502
TI  - Linkage analysis of Fanconi anaemia in Italy and mapping of the complementation
      group A gene.
AB  - Fanconi anaemia (FA) is an autosomal recessive disease characterised by genetic
      heterogeneity, with at least five complementation groups (FA-A to FA-E). The FAC
      gene has been cloned and localised to 9q22.3. The most frequent defective gene,
      FAA, was recently mapped to chromosome 16q24.3, in a region of 10 cM between
      D16S498 and the telomere. Eleven FA-A and 16 unclassified Italian families were
      analysed by microsatellite markers. To define the localisation of the FAA locus
      further, microsatellites were analysed at 16q24. All the families were consistent
      with linkage, the highest lod score being observed with D16S1320. Evidence for
      common haplotypes was obtained in two genetic isolates from the Brenta basin and
      the Naples region. Autozygosity mapping and haplotype analysis suggest that the
      FAA locus is distal to D16S305.

PMID- 9003503
TI  - Mutations in the gene encoding 21-hydroxylase detected by solid-phase
      minisequencing.
AB  - We have developed an assay based on solid-phase minisequencing to screen for the
      following seven point mutations in the gene CYP21 encoding 21-hydroxylase:
      Pro30Leu, I2-splice, Ile172Asn, Cluster-E6, Val281Leu, Gln318Stop, and Arg356Trp.
      5'-Biotinylated PCR products of CYP21 are bound to streptavidin-coated microtiter
      wells, where the minisequencing reaction takes place after denaturation of DNA.
      Depending on the sequence investigated, one specific 3H-labelled
      deoxyribonucleotide is incorporated to extend a detection primer. By using an
      appropriate set of detection primers, it is possible to screen the gene for
      several mutations within the same PCR amplificate. This fast and reliable method
      very clearly distinguishes between DNA from homozygous mutant, heterozygous, and
      normal individuals and is well suited for routine diagnosis of patients with 21
      hydroxylase deficiency and for carrier detection.

PMID- 9003504
TI  - The high mobility group I-C gene (HMGI-C): polymorphism and genetic localization.
AB  - We have identified a highly informative dinucleotide repeat in the 5'-flanking
      region of the human high mobility group I-C (HMGI-C) gene. This polymorphism
      consists of 18-37 copies of a (CT) repeat with an observed heterozygosity of 82
      83% in African Americans and Caucasians. Linkage analysis in CEPH pedigrees
      localized the HMGI-C gene to chromosome region 12q13-15 with no recombination
      observed between HMCI-C and markers D12S102 and D12S8.

PMID- 9003506
TI  - Association between common alleles of the low-density lipoprotein receptor gene
      region and interindividual variation in plasma lipid and apolipoprotein levels in
      a population-based sample from Rochester, Minnesota.
AB  - This paper presents an analysis of the relationship between variation in the low
      density lipoprotein receptor (LDLR) gene region and interindividual variation in
      plasma lipid and apolipoprotein levels in a sample representative of the adult
      population of Rochester, Minn. (217 females and 187 males aged 26 to 63). This
      relationship was analyzed by estimating the average excesses of alleles of the
      LDLR gene defined using RFLP markers both singly and simultaneously. We also used
      a cladistic approach to illustrate the consequences of incorporating evolutionary
      information into the analysis of genotype-phenotype relationships. Although
      results from both approaches supported the inference that common variation in the
      LDLR gene region associates with small effects on plasma lipid and apolipoprotein
      levels, only the cladistic approach provides direction for further work aimed at
      identifying the functional DNA sequence variations responsible for the observed
      associations.

PMID- 9003505
TI  - The T705I mutation of the low density lipoprotein receptor gene (FH Paris-9) does
      not cause familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is a genetic disease caused by mutations in
      the low-density lipoprotein receptor gene. Among the more than 200 mutations so
      far identified, the T705I substitution in exon 15, designated FH-Paris 9, has
      been previously described as an FH-causing mutation. During the course of
      denaturing gradient gel electrophoretic screening of exon 15 we have identified
      the T705I single-base substitution not only in an FH family but also in a
      control, normocholesterolemic population. Therefore, we conclude that FH-Paris 9
      is a missense mutation not associated with FH.

PMID- 9003507
TI  - Refinement of the dominant optic atrophy locus (OPA1) to a 1.4-cM interval on
      chromosome 3q28-3q29, within a 3-Mb YAC contig.
AB  - Dominant optic atrophy, type Kjer, is an autosomal dominant eye disease that is
      characterized by progressive optic atrophy with onset in early childhood,
      decrease of visual acuity, colour vision defects and centrocecal scotoma. By
      examination of 5 Danish families and the use of polymorphic markers, we have
      refined the localization of the OPA1 locus and assigned it to a 1.4-cM interval
      on chromosome 3q28-3q29, between markers D3S3669 and D3S3562. This localizes the
      gene on a 3-Mb YAC contig covering the disease locus. We have also located a
      possible candidate gene HRY to this contig.

PMID- 9003508
TI  - Characterization of more than 85% of cystic fibrosis alleles in the Greek
      population, including five novel mutations.
AB  - To completely characterize the spectrum of mutations in the cystic fibrosis
      transmembrane conductance regulator gene in Greek cystic fibrosis (CF) patients,
      we screened 500 CF chromosomes by denaturing gradient gel electrophoresis
      followed by direct sequencing. We identified 48 mutations, accounting for 85.6%
      of CF chromosomes. They included eight novel mutations, three of which we have
      described before and five (E822X, Y247X, 2752-26A-->G, 3152delT, and 2751 + T-
      >A), which are described in this report. The detection of such a high proportion
      of Greek CF mutations is important for improving prenatal and genetic diagnosis
      of CF in Greece.

PMID- 9003509
TI  - Molecular basis of variegate porphyria: a de novo insertion mutation in the
      protoporphyrinogen oxidase gene.
AB  - The porphyrias are disorders that result from the inherited or acquired
      dysregulation of one of the eight enzymes in the heme biosynthetic pathway.
      Variegate porphyria (VP) is characterized by deficiencies in protoporphyrinogen
      oxidase (PPO) and has recently been genetically linked (Z = 6.62) to the PPO gene
      on chromosome 1q21. In this study, we have identified two sequence variants in
      the PPO gene in a family with VP. The first is a neutral polymorphism at the -47
      position of intron 2; this polymorphism is present in the general population and
      is unlikely to underlie the VP phenotype. The second is a mutation in the PPO
      gene in a patient with VP; the mutation consists of an apparently de novo 2-bp
      insertion in exon 3 of PPO and results in a frameshift and downstream premature
      termination codon. These data establish that a frameshift mutation in PPO is the
      underlying mutation in this patient with VP and explain the sporadic occurrence
      of the phenotype in this family.

PMID- 9003510
TI  - Exclusion of the phosphoinositide-specific phospholipase C beta 3 (PLCB3) gene as
      a candidate for multiple endocrine neoplasia type 1.
AB  - The predisposing genetic defect in multiple endocrine neoplasia type 1 has been
      assigned to chromosomal region 11q13. Our previous attempts to identify the MEN1
      gene have resulted in the isolation of the phospholipase C beta 3 gene from the
      actual region. PLCB3 plays an important role in signal transduction and,
      moreover, shows loss of expression in some endocrine tumors, in accordance with a
      putative tumor suppressor gene function, and thus appears to be an excellent
      candidate for MEN1. We have therefore undertaken screening for constitutional
      mutations in individuals from MEN1 families. Several sequence alterations have
      been discovered, none of them however fulfilling the criteria for a disease
      related mutation. We can now exclude PLCB3 from candidacy as the MEN1 gene.

PMID- 9003511
TI  - Exclusion of the phosphatidylinositol-specific phospholipase C beta 3 (PLC beta
      3) gene as candidate for the multiple endocrine neoplasia type 1 (MEN 1) gene.
AB  - Multiple endocrine neoplasia type 1 (MEN 1) is inherited as an autosomal dominant
      disorder, characterized by hyperplasia and neoplasia in several endocrine organs.
      The MEN 1 gene, which is most probably a tumor suppressor gene, has been
      localized to a 900-kb region on chromosome 11q13. The human phosphatidylinositol
      specific phospholipase C beta 3 (PLC beta 3) gene, which is located within this
      region, was considered to be a good candidate for the MEN 1 gene. In this study,
      the structure and expression of the PLC beta 3 gene in MEN 1 patients were
      investigated in more detail, to determine its potential role in MEN 1
      tumorigenesis. Southern blot analysis, using blood and tumor DNA from affected
      persons from seven different MEN 1 families, did not reveal structural
      abnormalities in the PLC beta 3 gene. To detect possible point mutations, or
      other small structural aberrations, direct sequencing of PLC beta 3 cDNAs from
      two affected persons from two different MEN 1 families was performed, but no MEN
      1-specific abnormalities were revealed. Several common nucleotide sequence
      polymorphisms were detected in these cDNAs, proving that both alleles of the PLC
      beta 3 gene were expressed and analyzed. In conclusion, these results exclude the
      PLC beta 3 gene as a candidate gene for MEN 1.

PMID- 9003512
TI  - The IGHG3 gene shows a structural polymorphism characterized by different hinge
      lengths: sequence of a new 2-exon hinge gene.
AB  - Four of the five human IGHG genes (G1, GP, G2, and G4) display a hinge region
      consisting of a unique exon. In contrast, IGHG3 exhibits a different structure in
      which the hinge is constituted by four or, less frequently, three exons. We
      report here the nucleotide sequence of a new 2-exon hinge G3 gene found in a
      Mandenka individual from Eastern Senegal. A comparison of this sequence with that
      of 4-exon and 3-exon hinge G3 genes suggests that the 3-exon and 2-exon hinge
      forms arose independently by deletion events in a 4-exon hinge gene.

PMID- 9003513
TI  - Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of
      hepatic glucose-6-phosphate translocase.
AB  - The enzyme system glucose-6-phosphatase (EC 3.1.3.9) plays a major role in the
      homeostatic regulation of blood glucose. It is responsible for the formation of
      endogenous glucose originating from gluconeogenesis and glycogenolysis. Recently,
      chlorogenic acid was identified as a specific inhibitor of the glucose-6
      phosphate translocase component (Gl-6-P translocase) of this enzyme system in
      microsomes of rat liver. Glucose 6-phosphate hydrolysis was determined in the
      presence of chlorogenic acid or of new synthesized derivatives in intact rat
      liver microsomes in order to assess the inhibitory potency of the compounds on
      the translocase component. Variation in the 3-position of chlorogenic acid had
      only poor effects on inhibitory potency. Introduction of lipophilic side chain in
      the 1-position led to 100-fold more potent inhibitors. Functional assays on
      isolated perfused rat liver with compound 29i, a representative of the more
      potent derivatives, showed a dose-dependent inhibition of gluconeogenesis and
      glycogenolyosis, suggesting glucose-6-phosphatase as the locus of interference of
      the compound for inhibition of hepatic glucose production also in the isolated
      organ model. Gl-6-P translocase inhibitors may be useful for the reduction of
      inappropriately high rates of hepatic glucose output often found in non-insulin
      dependent diabetes.

PMID- 9003514
TI  - Structure-activity relationships of selective estrogen receptor modulators:
      modifications to the 2-arylbenzothiophene core of raloxifene.
AB  - The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor
      modulator which is currently under clinical evaluation for the prevention and
      treatment of postmenopausal osteoporosis. A series of raloxifene analogs which
      contain modifications to the 2-arylbenzothiophene core have been prepared and
      evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7
      breast cancer cell proliferation in vitro. Their ability to function as tissue
      selective estrogen agonists in vivo has been assayed in a short-term,
      ovariectomized (OVX) rat model with end points of serum cholesterol lowering,
      uterine weight gain, and uterine eosinophil peroxidase activity. These studies
      have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy
      substituents of raloxifene are important for receptor binding and in vitro
      activity, (2) small, highly electronegative 4'-substituents such as hydroxy,
      fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric
      bulk at the 4'-position leads to increased uterine stimulation in vivo, and (4)
      additional substitution of the 2-aryl moiety is tolerated while additional
      substitution at the 4-, 5-, or 7-position of the benzothiophene results in
      reduced biological activity. In addition, compounds in which the 2-aryl group is
      replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in
      vitro and in vivo biological activity qualitatively similar to that of
      raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl,
      and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in
      a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.

PMID- 9003515
TI  - Expeditious syntheses of sugar-modified nucleosides and collections thereof
      exploiting furan-, pyrrole-, and thiophene-based siloxy dienes.
AB  - A series of individual sugar-modified pyrimidine nucleosides including
      enantiomerically enriched 2',3'-dideoxynucleosides 14a-c (alpha and beta anomers
      of L- and D-series), 2',3'-dideoxy-4'-thionucleosides 21a-c (alpha and beta
      anomers of L- and D-series), and 2',3'-dideoxy-4'-azanucleosides 28a-c (beta
      anomers of L- and D-series) were synthesized, with uniform chemistry and high
      stereochemical efficiency, exploiting a triad of versatile heterocyclic siloxy
      dienes, namely, 2-(tert-butyldimethylsiloxy)furan (TBSOF), 2-(tert
      butyldimethylsiloxy)thiophene (TBSOT), and N-(tert-butoxycarbonyl)-2-(tert
      butyldimethylsiloxy)pyrrole (TBSOP). The synthetic procedure advantageously used
      both enantiomers of glyceraldehyde acetonide (D-1 and L-1) as sources of
      chirality and as synthetic equivalents of the formyl cation. The outlined
      chemistry also allowed for the rapid assemblage of a 30-member collection of
      racemic nucleosides (D,L-L) as well as one 15-member ensemble of chiral analogues
      (L-L), along with some related sublibraries.

PMID- 9003516
TI  - Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against
      both wild type and protease inhibitor resistant mutants of HIV.
AB  - Cyclic urea amides, a novel series of HIV-1 protease (HIV PR) inhibitors, have
      increased activity against drug-resistant mutants of the HIV PR. The design
      strategy for these inhibitors is based on the hypotheses that (i) the hydrogen
      bonding interactions between the inhibitor and the protease backbone will remain
      constant for wild-type and mutant enzymes and (ii) inhibitors which are capable
      of forming many nonbonded interactions, distributed throughout the active site,
      will experience a lower percent change in binding energy as a result of mutation
      in the target enzyme than those that form fewer interactions by partial
      occupation of the active site. The cyclic urea amide, SD146, forms 14 hydrogen
      bonds and 191 van der Waals contacts to HIV PR. SD146 is a very potent antiviral
      agent (IC90 = 5.1 nM) against wild-type HIV and maintains the same or improved
      level of high potency against a range of mutant strains of HIV with resistance to
      a wide variety of HIV protease inhibitors.

PMID- 9003517
TI  - Structure-activity relationships of cysteine-lacking pentapeptide derivatives
      that inhibit ras farnesyltransferase.
AB  - Mutational activation of ras has been found in many types of human cancers,
      including a greater than 50% incidence in colon and about 90% in pancreatic
      carcinomas. The activity of both native and oncogenic ras proteins requires a
      series of post-translational processing steps. The first event in this process is
      the farnesylation of a cysteine residue located in the fourth position from the
      carboxyl terminus of the ras protein, catalyzed by the enzyme farnesyltransferase
      (FTase). Inhibitors of FTase are potential candidates for development as
      antitumor agents. Through a high-volume screening program, the pentapeptide
      derivative PD083176 (1), Cbz-His-Tyr(OBn)-Ser(OBn)-Trp-DAla-NH2, was identified
      as an inhibitor of rat brain FTase, with an IC50 of 20 nM. Structure-activity
      relationships were carried out to determine the importance of the side chain and
      chirality of each residue. This investigation led to a series of potent FTase
      inhibitors which lack a cysteine residue as found in the ras peptide substrate.
      The parent compound (1) inhibited the insulin-induced maturation of Xenopus
      oocytes (concentration: 5 pmol/oocyte), a process which is dependent on the
      activation of the ras pathway.

PMID- 9003518
TI  - Synthesis and inhibition studies of sulfur-substituted squalene oxide analogues
      as mechanism-based inhibitors of 2,3-oxidosqualene-lanosterol cyclase.
AB  - The synthesis and biological evaluation of three new sulfur-substituted
      oxidosqualene (OS) analogues (1-3) are presented. In these analogues, C-11, C-15,
      or C-18 in the OS skeleton was replaced by sulfur. The sulfur position in the OS
      skeleton was chosen to disrupt one or more key processes involved in cyclization:
      (a) the folding of the B-ring into a boat conformation, (b) the anti-Markovnikov
      cyclization leading to the C-ring, or (c) the formation of the D-ring during the
      lanosterol biosynthesis. Enzyme inhibition kinetics using homogeneous mammalian
      oxidosqualene cyclases (OSC) were also examined for the previously reported S-19
      analogue 4. The four analogues were potent inhibitors of mammalian OSCs (IC50 =
      0.05-2.3 microM for pig and rat liver OSC) and fungal cell-free Candida albicans
      OSC (submicromolar IC50 values). In particular, the S-18 analogue 3 showed the
      most potent inhibition toward the rat liver enzyme (IC50 = 50 nM) and showed
      potent, selective inhibition against the fungal enzyme (IC50 = 0.22 nM, 10-fold
      more potent than the S-19 analogue 4). Thus, 3 is the most potent OSC inhibitor
      known to date. The Ki values ranged from 0.5 to 4.5 microM for pig OSC, with 3
      and 4 showing about 10-fold higher potency for rat liver OSC. Interestingly, the
      S-18 analogue 3 showed time-dependent irreversible inhibition with homogeneous
      pig liver OSC (kinact = 0.06 min-1) but not with rat OSC.

PMID- 9003519
TI  - Identification of high-potency neuropeptide Y analogues through systematic
      lactamization.
AB  - In the pursuit of potent analogues of neuropeptide Y (NPY) that are selective for
      the Y1 receptor subtype, two lactam bridge scans of a centrally truncated parent
      compound were synthesized. A single lactam bridge (gamma-carboxyl of Glu to
      epsilon-amino of Lys) extending from residues i to i + 3 or i to i + 4 of the
      proposed alpha-helical region (residues 25-31 of NPY) was introduced in des-AA7
      24[Gly6]NPY. Cyclogues (contraction of cyclic analogues), which were
      approximately one-half the size of native NPY, were initially screened for
      binding affinity at two discrete NPY receptor types using human neuroblastoma
      cell membranes, SK-N-MC and SK-N-BE2. Exploitation of the subtle differences
      present on each receptor type allowed for the identification of cyclogues which
      bound specifically to Y1 receptors with increased affinity when compared to the
      corresponding linear parent analogue, while one short Y1 specific cyclogue, des
      AA2,3,5,7-24cyclo-(26/29)[Gly6,Glu26,Lys2 9,Pro34]NPY, bound with Ki = 16 nM.
      Other cyclogues showed distinct preference for Y2 receptors and bound in the low
      nanomolar range. Functionally, the compounds inhibited the norepinephrine
      stimulated accumulation of cAMP indicating that all acted as agonists with
      varying potencies.

PMID- 9003520
TI  - Camptothecin and minor-groove binder hybrid molecules: synthesis, inhibition of
      topoisomerase I, and anticancer cytotoxicity in vitro.
AB  - The synthesis, characterization, inhibitory activity against topoisomerase I, and
      biological evaluation of a series of 14 camptothecin derivatives of
      polypyrrolecarboxamide (lexitropsin) conjugates of two structural classes: (A)
      camptothecin-NHCO-lexitropsin 44-51 and (B) camptothecin-CONH-lexitropsin 38-43
      are described. All 16 compounds tested, 14 conjugates plus two functionalized
      camptothecin controls, inhibit topoisomerase I in the concentration range 1.12
      16.6 microM that divide into three distinct categories based on activity. The
      most active enzyme inhibitors belong to structure class A with either cationic
      dimethylaminium or neutral amide end groups. Generally class B conjugates are
      less effective in inhibiting topoisomerase I. Cytotoxic potencies of the drugs
      was tested against four representative human tumor cell lines: SKOV3, SKLVB,
      HT29, and KB. All 16 drugs gave measurable IC50 values against the KB cell line
      and fell into two categories with IC50 values of 0.049-0.66 microM (largely
      structure class B) and 1.0-48 microM (largely class A). Thus the class B
      conjugates, while less potent against the enzyme, contain two of the most potent
      drugs, 38 and 39, against KB cell lines. In contrast, in the case of the cell
      lines SKOV3 and HT29 there was a general correlation between the better
      topoisomerase inhibitors and their cell cytotoxicities.

PMID- 9003521
TI  - Synthesis and protein kinase C inhibitory activities of balanol analogs with
      replacement of the perhydroazepine moiety.
AB  - Balanol is a potent protein kinase C (PKC) inhibitor that is structurally
      composed of a benzophenone diacid, a 4-hydroxybenzamide, and a perhydroazepine
      ring. A number of balanol analogs in which the perhydroazepine moiety is replaced
      have been synthesized and their biological activities evaluated against both PKC
      and cAMP-dependent kinase (PKA). The results suggested that the activity and the
      isozyme/kinase selectivity of these compounds are largely related to the
      conformation about this nonaromatic structural element of the molecules.

PMID- 9003522
TI  - Butitaxel analogues: synthesis and structure-activity relationships.
AB  - N-Acyl analogues 8, 9, and 12-26 of butitaxel (3) were prepared in one or two
      steps from amines 5 and 6 through Schotten-Baumann acylation. Seventeen novel
      analogues, consisting of aliphatic carbamates, alicyclic amides, and
      heteroaromatic amides, were synthesized. They were evaluated for their in vitro
      ability to stimulate the formation of microtubules, their cytotoxicity toward B16
      melanoma cells, and their solubility in water. The most potent analogue found in
      this study was N-debenzoyl-N-(2-thenoyl)butitaxel (20), possessing ca. 2-fold
      better tubulin assembly properties and cytotoxic activity against B16 melanoma
      cells than paclitaxel. Compound 20 was ca. 25 times more water soluble than
      paclitaxel.

PMID- 9003523
TI  - Coumarin-based inhibitors of HIV integrase.
AB  - The structures of a large number of HIV-1 integrase inhibitors have in common two
      aryl units separated by a central linker. Frequently at least one of these aryl
      moieties must contain 1,2-dihydroxy substituents in order to exhibit high
      inhibitory potency. The ability of o-dihydroxy-containing species to undergo in
      situ oxidation to reactive quinones presents a potential limitation to the
      utility of such compounds. The recent report of tetrameric 4-hydroxycoumarin
      derived inhibitor 5 provided a lead example of an inhibitor which does not
      contain the catechol moiety. Compound 5 represents a large, highly complex yet
      symmetrical molecule. It was the purpose of the present study to determine the
      critical components of 5 and if possible to simplify its structure while
      maintaining potency. In the present study, dissection of tetrameric 5 (IC50 = 1.5
      microM) into its constituent parts showed that the minimum active pharmacophore
      consisted of a coumarin dimer containing an aryl substituent on the central
      linker methylene. However, in the simplest case in which the central linker aryl
      unit consisted of a phenyl ring (compound 8, IC50 = 43 microM), a significant
      reduction in potency resulted by removing two of the original four coumarin
      units. Replacement of this central phenyl ring by more extended aromatic systems
      having higher lipophilicity improved potency, as did the addition of 7-hydroxy
      substituents to the coumarin rings. Combining these latter two modifications
      resulted in compounds such as 3,3'-(2-naphthalenomethylene)bis[4,7
      dihydroxycoumarin] (34, IC50 = 4.2 microM) which exhibited nearly the full
      potency of the parent tetramer 5 yet were structurally much simpler.

PMID- 9003525
TI  - Frequencies of X-ray induced pericentric inversions and centric rings in human
      blood lymphocytes detected by FISH using chromosome arm specific DNA libraries.
AB  - Frequencies of intra-chromosomal exchanges (pericentric inversions and centric
      rings) and inter-chromosomal exchanges (dicentrics and translocations) in X
      irradiated (2.5 Gy) human lymphocytes have been estimated. To detect these events
      we employed FISH (fluorescence in situ hybridization) technique and arm specific
      painting probes for chromosomes #1 and #3. The ratio between centric rings and
      pericentric inversions was found to be about 1. For intra-changes to inter
      changes, the ratio (F) was between 6 and 9. Based on the total number of colour
      junctions involving chromosomes #1 and #3 it was found that exchanges between the
      arms of the same chromosome occur about 8.7 times more than inter-chromosomal
      exchanges calculated on the basis of the DNA content of the chromosomes and
      random induction of aberrations in the total genome. Chromosomal organization in
      interphase nucleus appears to promote the formation of more intra-changes than
      inter-changes following X-irradiation, most probably due to close proximity of
      the two arms of a chromosome.

PMID- 9003524
TI  - 3-[[(4-Aryl-1-piperazinyl)alkyl]cyclohexyl]-1H-indoles as dopamine D2 partial
      agonists and autoreceptor agonists.
AB  - A series of arylpiperazines and tetrahydropyridines joined to indoles by
      semirigid cycloalkyl spacers were prepared. Target compounds were studied for
      their ability to bind to the DA D2 receptor in vitro and to inhibit dopamine
      synthesis and spontaneous locomotor activity in rats. Effects of tether length
      and relative stereochemistry were assessed for a series of 2-pyridylpiperazines.
      The cyclohexylethyl spacer was found to be the most active in the series. Further
      studies explored effects of changes in the arylpiperazine and indole portions of
      the molecule. From these studies trans-2-[[4-(1H-3-indolyl)cyclohexyl]ethyl]-4-
      (2-pyridinyl)piperazine (30a) was selected for further evaluation. It was
      characterized as a partial agonist of DA D2 receptors in vitro and caused
      decreases in dopamine synthesis and release as well as dopamine neuronal firing.
      Compound 30a was shown to be devoid of behavioral effects associated with
      postsynaptic DA D2 receptor activation. Furthermore, compound 30a was shown both
      to decrease DA synthesis and to inhibit Sidman avoidance responding in squirrel
      monkeys. These findings suggest that DA D2 partial agonists with the appropriate
      level of intrinsic activity can act to decrease dopamine synthesis and release
      and may have potential utility as antipsychotic agents.

PMID- 9003526
TI  - Both bovine and rabbit lymphocytes conditioned with hydrogen peroxide show an
      adaptive response to radiation damage.
AB  - We have carried out experiments to study the possible induction of an adaptive
      response in cultured bovine and rabbit lymphocytes conditioned with subtoxic
      doses of hydrogen peroxide after stimulation and subsequently challenged with 1
      Gy of X-rays. Peroxide treatment was given at different doses 48 h after the
      addition of PHA to stimulate the cells. A protective effect of pre-exposure to
      H2O2 against radiation damage detected as micronuclei in binucleated cells was
      evident for all the animals tested regardless the dose of H2O2 used, although
      this effect was in general of greater magnitude in bovine than in rabbit cells.
      These results lend further support to our previous finding in human lymphocytes
      that DNA single strand breaks induced by H2O2 (most likely due to the generation
      of hydroxyl radicals) is the most important lesion to trigger the adaptive
      response.

PMID- 9003527
TI  - The polymorphism of GSTM1, mutagen sensitivity in colon cancer and healthy
      control.
AB  - The aim of this article is to study the relationship between GSTM1 polymorphism
      and colon cancer and to compare the chromosomal breakage induced by mutagen in a
      colon cancer group and healthy controls. Using PCR to identify the GSTM1
      genotype, we found the frequency of GSTM1- in colon cancer (n = 19) and control
      group (n = 23) was 36.8% and 26.1%, respectively (p > 0.05, chi 2-test). The
      bleomycin-induced chromosomal breakage (break/cell) in the patient group was 0.75
      +/- 0.29, and in the control group 0.42 +/- (0.24) (p < 0.05, t-test). The
      percentage of mutagen sensitivity (b/c > 0.8) in the patient group (68%) was 4
      times as high as that in the control group (20%). The mutagen hypersensitivity
      (b/c > 1.0) in the patient group (47%) was 5 times as high as that in the control
      group (12%). The odds radio was 6.6.

PMID- 9003529
TI  - Chromosomal breakage correlates with delayed lethality in normal and ataxia
      telangiectasia cell lines treated with bleomycin.
AB  - Cytogenetic damage and cytotoxicity produced by a range of acute treatments with
      bleomycin (BLM) were investigated in three B-lymphoblastoid cell lines: EM-OC, PA
      AT and CP-NC; established from heterozygous, and homozygous, ataxia
      telangiectasia (AT) and normal donors, respectively. The following endpoints were
      studied: (1) the maximum (initial) yields of different classes of chromosomal
      aberrations (CA) produced in G2-phase; (2) the percentage distributions of cells
      within bins with different numbers of CA; (3) short-term (0-48 h) viability and
      proliferation; and (4) (delayed) lethality, as measured by a modified limiting
      dilution assay. While only slight losses of short-term viability and
      proliferation were detectable after standard BLM pulse-treatment at 25 or 100
      micrograms/ml (results for latter dose given in parentheses), both regimes
      subsequently led to intense lethality as follows: CP-NC, 79.3% (95.1%); EM-OC,
      90.4% (96.7%) and PA-AT, 98.4% (99.9%). Relative lethality after the respective
      BLM treatments increased 6.2 x (48.3 x) among PA-AT cells more than in controls
      resembling the corresponding ratios for chromosome breaks (csb) of 7.0 x (30.9
      x), more than those for chromatid breaks (ctb) of 3.1 x (2.7 x). EM-OC exhibited
      slightly increased relative lethality after the respective BLM treatments at 2.15
      x (1.45), and increased aberration sensitivities for csb of 3.0 x (14.0), while
      the corresponding ratios for ctb were actually lower at 0.66 x (0.50 x).
      Significant correlations were observed between lethality and both, the yields of
      most types of chromosomal aberrations (excepting unambiguous exchanges) and also,
      the percentages of cells bearing CA.

PMID- 9003528
TI  - A 3 milliTesla 60 Hz magnetic field is neither mutagenic nor co-mutagenic in the
      presence of menadione and MNU in a transgenic rat cell line.
AB  - The mechanisms by which an electromagnetic field (EMF) influences biological
      material are poorly understood. One potentially important model suggests that a
      magnetic field can stabilize free radicals in such a way as to permit their
      dispersement rather than their return to the ground state (Okazaki et al., 1988;
      Scaiano, 1995). We have tested this hypothesis by examining mutagenesis in the E.
      coli lacI gene target carried in the Big Blue rat embryo fibroblast cell line, R2
      lambda LIZ. Mutant frequencies were determined in cells exposed to a magnetic
      field, cells pretreated with the mutagens N-methylnitrosourea (MNU) or 2-methyl
      1,4-naphthoquinone (menadione), prior to being held in a 60 Hz 3 milliTesla (mT)
      magnetic field and cells concurrently exposed to the mutagens and the magnetic
      field. Menadione was selected because its mutagenic mechanism involves the
      formation of free radicals, while MNU is an alkylating agent not thought to act
      through radical formation. According to the radical stabilization hypothesis the
      application of a magnetic field to menadione treated cells would accentuate the
      mutagenic effects. Our results failed to indicate that the magnetic field affects
      mutagenesis by the oxygen-radical mediated mutagen, menadione.

PMID- 9003530
TI  - Genetic analysis of the cause of gastroschisis in the HLG mouse strain.
AB  - An inbred mouse strain HLG shows a high incidence of gastroschisis after X-ray
      exposure to the zygotes. About 11% of the fetuses display this malformation after
      irradiation with 1 Gy. The C57BL-strain does not show the increased frequency of
      gastroschisis after radiation-exposure to the zygotes. The genetic background of
      this malformation was investigated in a backcross of HLG x C57BL females to HLG
      males. The pregnant HLG x C57BL females were irradiated in a stage in which the
      (HLG x C57BL) x HLG [BC1] embryos were in the 1-cell stage. The frequency of
      gastroschisis in the BC1 generation was compared with a genetic model of a single
      recessive mutation with 11% penetrance. This frequency does not fit a single
      locus inheritance. The number of loci involved was estimated to be about two or
      three. HLG mouse strain may be a valuable animal model in the study of polygenic
      traits.

PMID- 9003531
TI  - Molecular analysis of lacI mutations in Rat2 cells exposed to 7,12
      dimethylbenz[a]anthracene: evidence for DNA sequence and DNA strand biases for
      mutation.
AB  - The Rat2 cell line carries 50-70 stably integrated copies per cell of a
      lambda/lacI shuttle vector as a target for mutagenicity testing. Rat2 cells were
      exposed to 1 and 10 micrograms/ml of 7,12-dimethylbenz[a]anthracene (DMBA) for 24
      h at 37 degrees C in the presence of primary rat hepatocytes, and grown to
      confluence. The shuttle vector was rescued from untreated and mutagen-treated
      cells and mutant frequencies were determined. The low and high doses of DMBA
      induced mutant frequencies that were 7-fold (25 +/- 4.9 x 10(-5)) and 33-fold
      (127 +/- 19.9 x 10(-5)) higher, respectively, than the spontaneous mutant
      frequency (3.8 +/- 0.7 x 10(-5)). DNA sequence analysis of the DMBA-induced lacI-
      mutants indicated that they contained mainly basepair substitution mutations at
      A:T and G:C, and that A:T-->T:A and G:C-->T:A transversions were the predominant
      types. In addition, 23 of 28 (82%) A:T basepair substitution mutations occurred
      with the mutated dA, the putatively adducted base, on the coding strand.
      Furthermore, 20 of the 28 (71%) A:T mutations had the mutated dA flanked 5' by a
      dC, and 17 of these were A:T-->T:A transversions, suggesting a sequence
      preference for this mutation. Except for a higher proportion of G:C-->A:T
      transitions in the low dose data, the mutational profiles from low and high doses
      of DMBA were similar. These results indicate that DMBA mutagenesis in the lacI
      gene of Rat2 cells displays distinct DNA sequence and DNA strand preferences.

PMID- 9003532
TI  - Mutagenic analysis of 2,3-diaminophenazine and 2-amino-3-hydroxyphenazine in
      Salmonella strains expressing different levels of O-acetyltransferase with and
      without plant and mammalian activation.
AB  - 2,3-Diaminophenazine (DAP) and 2-amino-3-hydroxyphenazine (AHP) are products
      generated from oxidative-type phenylenediamine hair dyes and are also present in
      pesticide formulations as contaminants. Earlier studies demonstrated that DAP and
      AHP were mutagenic in Salmonella typhimurium strains after mammalian microsomal
      activation. Plant systems can activate structurally similar arylamines. S.
      typhimurium strains have been developed that express elevated levels of acetyl
      CoA: N-hydroxyarylamine O-acetyltransferase (OAT). O-acetyltransferase expression
      is necessary for the generation of the ultimate arylamine promutagen after plant
      activation. A number of arylamines including 2-aminofluorene, benzidine and 4
      aminobiphenyl were activated by plant cells into mutagens in the OAT over
      expressing S. typhimurium strain, YG1024. The objectives of this research were to
      examine the mutagenicity of DAP and AHP with mammalian or plant activation in
      Salmonella strains with different acetyltransferase activities. The hypothesis
      tested was whether and to what degree a metabolite of DAP or AHP could serve as a
      substrate for bacterial O-acetyltransferase and induce mutation in Salmonella.
      DAP and AHP without activation induced both frameshift and base pair substitution
      mutations in S. typhimurium strains that exhibited elevated levels of O
      acetyltransferase activity. The mutagenicity of DAP and AHP were greatly enhanced
      with mammalian hepatic microsomal activation resulting in a preferential
      induction of frameshift mutations. With the hisD3052 allele as the gene target,
      S9-activated DAP induced frameshift mutations in YG1024 and TA98 as well as the
      OAT deficient strain TA98/1,8-DNP6. S9-activated AHP induced mutation only in the
      OAT over-expressing strain, YG1024. With the hisG46 allele, O-acetyltransferase
      activity was necessary for the metabolism of DAP and AHP to products that induce
      base pair substitution mutations. An intriguing finding of this work was the
      antimutagenic capacity of TX1MX, a plant cell-free activation mixture. TX1MX
      repressed the mutagenic activity of DAP and AHP at frameshift and base pair
      substitution mutation targets.

PMID- 9003533
TI  - Amino acids excess increase SCEs in human lymphocytes.
AB  - The effects of 21 amino acids on sister-chromatid exchanges (SCEs) in human
      lymphocytes were investigated. Addition of each of the 21 amino acids, originally
      in a composition of the culture medium RPMI 1640, at three different
      concentrations (10 micrograms/ml, 50 micrograms/ml and 100 micrograms/ml) caused
      a dose-independent increase in SCE frequency. The results indicated that amino
      acids, although indispensable for cells in vivo and in vitro, may be SCE-inducing
      agents.

PMID- 9003534
TI  - Structure-activity and mechanistic relationships: the effect of chemical overlap
      on structural overlap in data bases of varying size and composition.
AB  - Similarities between structures in SAR models derived from different data bases,
      termed 'structural overlap', can be used for determining mechanistic
      similarities, e.g., mutagenicity vs. carcinogenicity. However, the structural
      overlap may be affected by the proportion of common chemicals in the data bases,
      termed 'chemical overlap'. In order to refine our ability to determine
      mechanistic similarities, we investigated the relationship between chemical and
      structural overlap as well as the effect of the ratio of active to inactive
      chemicals and data base size on that relationship, using a data base of
      Salmonella mutagenicity. A linear relationship between chemical overlap and
      structural overlap with a slope of 0.332 was found. For data bases of 210, 300
      and 390 chemicals, this relationship was consistent. Differences in ratios of
      active to inactive chemicals, i.e., 1:2, 1:1 and 2:1, did not appear to affect
      the linear model. We can use this relationship to adjust for chemical overlap
      when examining the structural overlap of data bases developed for different
      endpoints to determine the extent of mechanistic similarities.

PMID- 9003535
TI  - MutS interaction with mismatch and alkylated base containing DNA molecules
      detected by optical biosensor.
AB  - An optical biosensor was used to monitor interactions between the Escherichia
      coli DNA mismatch repair molecule MutS and various immobilized oligonucleotides.
      While associating poorly with single-stranded DNA, MutS was capable of rapid
      association/dissociation from homoduplex DNA. The interaction of MutS with
      oligonucleotide 30-mers containing single site mismatches demonstrated that
      during the dissociation phase, MutS binding was greatest to a G-G mismatch,
      followed by G-T > A-A > C-T, A-C. Binding to A-G, T-T and C-C mispairs was
      marginally higher than that seen between MutS and homoduplex DNA. The ability of
      MutS to interact with 30-mers containing alkylated bases was also tested. While
      binding to O6-methyl-G-C, or to O4-methyl-T-A base pairs was similar to that of
      homoduplex DNA, strong binding was seen to a O6-methyl-G-T mispair. O4-methyl-T
      G, however, was poorly recognized by MutS, with relative binding affinity similar
      to homoduplex DNA, predicting poor in vivo recognition of O4-methyl-T-G by MutS.
      Interestingly, MutS demonstrated a relatively high affinity for an 1,N6-etheno-A
      T containing homoduplex. Thus, in allowing rapid evaluation of interactions
      between such molecules, the biosensor will be useful to structure-function
      analyses.

PMID- 9003537
TI  - Reduced expression of mature TGF beta 1 correlates with the suppression of rat
      hepatocyte apoptosis by the peroxisome proliferator, nafenopin.
AB  - Non-genotoxic carcinogens cause cancer without damaging the DNA. Peroxisome
      proliferators (PPs) are a class of potent rodent non-genotoxic hepatocarcinogens
      that may act by perturbing hepatocyte growth regulation. Previously, we have
      shown that although cultured rat hepatocytes degenerate rapidly in culture, their
      survival can be reversibly maintained by the PP nafenopin. This prolonged
      survival is associated with a decrease in the number of hepatocytes displaying
      the chromatin condensation characteristic of apoptosis. The addition of the
      negative growth regulator TGF beta-1 induced high levels of hepatocyte apoptosis
      but nafenopin was able to suppress this TGF beta-1 induced apoptosis. These data
      suggested that increased levels of mature TGF beta-1 may be involved in the
      signalling of the apoptosis seen in degenerating hepatocyte cultures. To test
      this hypothesis, we carried out Western blot analyses using a anti-TGF beta 1
      antibody. There was an increase (p = 0.014) in expression of mature TGF beta 1 in
      degenerating rat hepatocyte cultures compared with hepatocyte cultures surviving
      in the presence of nafenopin. However, there was a concomitant decrease (p =
      0.024) in TGF beta 1-latency activated protein (TGF beta 1-LAP), the precursor of
      the active, mature form. Immunocytochemistry confirmed that TGF beta 1/TGF beta 1
      LAP expression was predominantly in the hepatocytes displaying apoptotic
      morphology although expression was detected also in non-parenchymal liver cells.
      The immunocytochemistry data indicate that TGF beta 1 is involved during the
      onset of hepatocyte apoptosis and that the PP nafenopin can impinge on this cell
      death pathway. TGF beta 1-LAP, probably produced mainly by the non-parenchymal
      liver cells, may be processed less efficiently to the mature, active form in the
      presence of nafenopin, although more data are required to confirm this
      hypothesis.

PMID- 9003536
TI  - Towards validation of the Big Blue transgenic mouse mutagenesis assay: the
      mutational spectrum of ex vivo pinpoint mutant plaques.
AB  - To explore further the origin of spontaneous mutations recovered with the Big
      Blue transgenic mouse mutagenesis assay, the spectrum of ex vivo mutations from
      pinpoint mutant plaques was determined and compared with the spectrum of
      putatively mouse-derived mutations from circular, mutant plaques. The entire lacI
      gene and lacZ operator region from 62 pinpoint blue plaques was sequenced. The
      observed mutational spectrum of pinpoint mutants differed significantly from that
      seen in circular mutants (p < 0.0001). Only four percent of the mutations were
      transitions at CpG sites whereas this type of mutation was the most common (35%)
      in circular mutants. Microdeletions/microinsertions were seen more frequently in
      pinpoint mutants relative to circular mutants. Four base pair deletion/insertion
      events at the E. coli hotspot tandem repeats were seen in 10 of 62 (16%) pinpoint
      mutants and minor hotspots of mutation were observed at bp 141 and 1110. The
      mutational spectrum of pinpoint mutants provides further evidence that most
      circular mutants originate in mouse.

PMID- 9003538
TI  - Characterization of the adaptive response to ionizing radiation induced by low
      doses of X-rays to Vibrio cholerae cells.
AB  - Pretreatment with sublethal doses of X-rays induced an adaptive response in
      Vibrio cholerae cells as indicated by their greater resistance to the subsequent
      challenging doses of X-irradiation. The adaptive response was maximum following a
      pre-exposure dose of 1.7 Gy X-rays and an optimum incubation period of 40 min at
      37 degrees C. Pre-exposure to a sublethal dose of 1.7 Gy X-rays made the Vibrio
      cholerae cells 3.38-fold more resistant to the subsequent challenge by X-rays.
      Pretreatment with a sublethal dose of hydrogen peroxide offered a similar degree
      of protection to the bacterial cells against subsequent treatment with
      challenging doses of X-ray radiation. However, exposure of Vibrio cholerae cells
      to mild heat (42 degrees C for 10 min) before X-ray irradiation decreased their
      survival following X-irradiation.

PMID- 9003540
TI  - Anti-recombinogenic and convertible co-mutagenic effects of (E)-5-(2-bromovinyl)
      2'-deoxyuridine (BVDU) and other 5-substituted pyrimidine nucleoside analogs in
      S. cerevisiae MP1.
AB  - In experiments using yeast, without addition of an external metabolic activation
      system, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was co-mutagenic and showed
      an insignificant anti-recombinogenic effect in combination with triethylene
      melamine (TEM). In the presence of activating S9-mix, the anti-recombinogenicity
      and co-mutagenicity could clearly be seen. At higher concentrations the co
      mutagenic effect was converted into anti-mutagenicity. The other three 5
      substituted pyrimidine nucleoside analogs were tested only in the presence of
      activating S9-mix and showed similar effects. As TEM is a direct alkylating agent
      that is inactivated by liver microsomes, the higher activity in presence of S9
      mix can be interpreted as resulting from metabolic activation of the 5
      substituted pyrimidine nucleoside analogs. In previous experiments using yeast
      bacteria, Drosophila or mice, tumor promoters were co-recombinogenic/anti
      mutagenic, and co-carcinogens were co-mutagenic/anti-recombinogenic. Thus, there
      is not only an operational difference between tumor promoters and co-carcinogens
      but a real difference in respect to their genetic effectiveness. As up to now
      only co-carcinogens have shown co-mutagenic and anti-recombinogenic effects, it
      is perhaps possible that, within a certain concentration range, 5-substituted
      pyrimidine nucleoside analogs may have co-carcinogenic activity in
      carcinogenicity tests. At higher concentrations the co-carcinogenic effect may be
      converted into an anti-carcinogenic one.

PMID- 9003539
TI  - Characterization of mutations induced by 300 and 320 nm UV radiation in a rat
      fibroblast cell line.
AB  - The cytotoxic and mutagenic activities of monochromatic ultraviolet light (UV) at
      four wavelengths (254, 290, 300 and 320 nm) were determined using a rat
      fibroblast cell line CREF stably infected with a retroviral vector carrying the
      neo and HSV-tk markers. In this system, mutations can be positively detected as
      acyclovir-resistant colonies. Although the action spectra for these activities
      closely fit some of the previously reported spectra for photochemical DNA
      modifications, erythema, cell killing and mouse skin carcinogenesis, they diverge
      at 320 nm from the absorption spectrum for DNA and the action spectrum for
      bacterial inactivation and mutagenesis. Structural comparison of the HSV-tk
      mutants detected after irradiation with 300 and 320 nm UV revealed (1) CC dimers
      and C oligomers as predominant targets at both wavelengths; (2) increased
      incidence of relatively large deletions at 300 nm; and (3) greatly increased
      frequency of tandem double mutations at both wavelengths and of clustered
      multiple mutations at 320 nm. These results suggest the involvement of distinct
      mechanisms specifically operating, or becoming evident, in UV-mediated
      mutagenesis at these different wavelengths in mammalian cells.

PMID- 9003542
TI  - A role for methyl chloride in evolution?

PMID- 9003541
TI  - Comparison of the molecular characteristics of lacZ transgenic mouse mutations
      detected by visual and positive selection.
AB  - lacZ gene mutations in the transgenic Muta Mmouse can be detected by two
      different selection systems. While mutant frequencies recovered by phenyl-beta-D
      galactoside (P-gal) selection are comparable with those obtained using 5-bromo-4
      chloro-3-indolyl beta-D-galactopyranoside (X-gal) as substrate for beta
      galactosidase, there may still be differences at the molecular level in the
      mutations detected by these two methods. Accordingly, we have examined a spectrum
      of mutants recovered from the X-gal system by regrowing these mutants on the P
      gal plates. All colourless X-gal mutants grew normally on the P-gal plates.
      However, 11 out of 53 single light blue mutants, which express partial beta
      galactosidase activity, produce few or no plaques on the P-gal plates, indicating
      the possible loss of some mutations using the positive selection system. Further
      analysis of mutant phenotypes and base changes indicates that such loss is not
      mutation-type specific. Our data suggest that the positive selection method can
      detect the majority of lacZ mutations detectable by visual selection and is more
      efficient at detecting mutants within a reduced range of beta-galactosidase
      activity.

PMID- 9003543
TI  - Haematuria: intravenous urography, ultrasound or both?
AB  - PURPOSE: To compare the diagnostic value of intravenous urography (IVU),
      ultrasound (US) and their combination in detecting upper urinary tract
      malignancies in patients with haematuria. MATERIALS AND METHODS: In a prospective
      study, 360 consecutive patients who consulted the urologist for haematuria
      without renal colic were scheduled for IVU and US on the same day. The two
      procedures were performed by two different radiologists and reported
      independently. Histology or clinical follow-up of one year served as the gold
      standard. RESULTS: 63 patients dropped out. Of the remaining 297 patients, 9 (3%)
      had a malignancy in the upper urinary tract. Sensitivity and specificity with
      regard to the upper urinary tract pathology were 67% and 91% for IVU and 56% and
      94% for US, respectively. For both techniques combined this was 79% and 88%,
      respectively. CONCLUSION: An acceptable sensitivity for detecting upper urinary
      tract malignancies is obtained only by combining IVU and US.

PMID- 9003544
TI  - Chondrosarcoma of the skull base: CT, MR and pathological features.
AB  - We report on CT and MR image findings of a skull base chondrosarcoma. Chondroid
      mineralisation, a histological feature of chondrosarcoma, can be recognised on CT
      and is, together with the off-midline position of the tumour, the most
      characteristic finding. Differentiation is usually made by histological and
      immunocytochemical staining. Surgery, proton radiation therapy and stereotactic
      single high-dose irradiation have been used to treat patients with
      chondrosarcoma. It is worth mentioning that it was likely that the chondrosarcoma
      in our patient represented a malignant degeneration of an enchondroma that had
      been resected 30 years earlier.

PMID- 9003545
TI  - Repriming and activation alter the frequency of stereotyped discrete Ca2+ release
      events in frog skeletal muscle.
AB  - 1. Brief localized elevations in myoplasmic [Ca2+] (Ca2+ sparks) in individual
      sarcomeres of voltage-clamped frog skeletal muscle fibres were examined by laser
      scanning confocal microscopy. 2. Fibres held at 0 mV were briefly repolarized to 
      90 mV (repriming pulse) to restore only a small fraction of sarcoplasmic
      reticulum (SR) calcium release. Subsequent depolarization to 0 mV (test pulse)
      caused the appearance of small numbers of Ca2+ sparks at different sarcomeres
      from pulse to pulse. Increasing the repriming time resulted in an increase in the
      frequency of occurrence of the Ca2+ sparks. 3. The amplitude and spatio-temporal
      extent of the Ca2+ sparks were independent of the repriming time and test pulse
      voltage. Ca2+ sparks recorded during small depolarizations of fibres held at -90
      mV had a similar amplitude and spatio-temporal extent as those recorded after
      brief repriming of the same fibre held at 0 mV. 4. We conclude that stereotyped
      Ca2+ sparks underlie calcium release at all voltages and all extents of
      repriming. The amplitude of Ca2+ release is thus graded by the frequency but not
      by the amplitude or spatio-temporal extent of the individual SR Ca2+ release
      events.

PMID- 9003546
TI  - Spatially non-uniform Ca2+ signals induced by the reduction of transverse tubules
      in citrate-loaded guinea-pig ventricular myocytes in culture.
AB  - 1. Ratiometric confocal microscopy and the whole-cell patch clamp technique were
      used to simultaneously record intracellular Ca2+ transients and membrane currents
      from guinea-pig ventricular myocytes. Intracellular dialysis with the low
      affinity Ca2+ buffer citrate enabled us to record and analyse Ca2+ transients
      caused by Ca2+ influx alone and by additional Ca2+ release from the sarcoplasmic
      reticulum (SR) in the same cell. 2. In freshly isolated adult myocytes (used
      within 1-4 h of isolation) both types of Ca2+ transients ('Ca2+ entry' and 'Ca2+
      release' transients) were spatially uniform regardless of the Ca2+ current (ICa)
      duration. In contrast, Ca2+ transients in short-term cultured (1-2 days) myocytes
      exhibited marked spatial inhomogeneities. ICa frequently evoked Ca2+ waves that
      propagated from either or both ends of the cardiac myocyte. Reduction of the ICa
      duration caused Ca2+ release that was restricted to one of the two halves of the
      cell. 3. Analysis of the Ca2+ entry signals in freshly isolated and short-term
      cultured myocytes indicated that the spatial properties of the Ca2+ influx signal
      were responsible for the spatial properties of the triggered Ca2+ release from
      the SR. In freshly isolated ventricular myocytes Ca2+ influx was homogeneous
      while in short-term cultured cells pronounced Ca2+ gradients could be found
      during Ca2+ influx. Spatial non-uniformities in the amplitude of local Ca2+ entry
      transients were likely to cause subcellularly restricted Ca2+ release. 4. The
      changes in the spatial properties of depolarization-induced Cai2+ signals during
      short-term culture were paralleled by a decrease (to 65%) in the total cell
      capacitance. In addition, staining the sarcolemma with the membrane-selective dye
      Di-8-ANEPPS revealed that, in cultured myocytes, t-tubular membrane connected
      functionally to the surface membrane was reduced or absent. 5. These results
      demonstrate that the short-term culture of adult ventricular myocytes results in
      the concomitant loss of functionally connected t-tubular membrane. The lack of
      the t-tubular system subsequently caused spatially non-uniform SR Ca2+ release.
      Evidence is presented to show that in ventricular myocytes lacking t-tubules non
      uniform SR Ca2+ release was, most probably, the result of inhomogeneous Ca2+
      entry during ICa. These findings directly demonstrate the functional importance
      of the t-tubular network for uniform ventricular Ca2+ signalling.

PMID- 9003547
TI  - Subcellular properties of triggered Ca2+ waves in isolated citrate-loaded guinea
      pig atrial myocytes characterized by ratiometric confocal microscopy.
AB  - 1. Spatiotemporal aspects of subcellular Ca2+ signalling were studied in cultured
      adult guinea-pig atrial myocytes. A mixture of the Ca2+ indicators fluo-3 and
      Fura Red in combination with laser-scanning confocal microscopy was used for
      [Ca2+]i measurements while membrane currents were recorded simultaneously. 2. In
      citrate-loaded atrial myocytes not every Ca2+ current (ICa) could trigger Ca2+
      release from the sarcoplasmic reticulum (SR). Two types of Ca2+ signals could be
      observed: Ca2+ transients resulting from (i) Ca2+ influx alone and (ii)
      additional Ca2+ release. 3. Ca2+ release elicited by voltage steps of 100-150 ms
      duration was either apparently homogeneous or propagated as Ca2+ waves through
      the entire cell. With brief ICa (50-75 ms), Ca2+ waves with limited subcellular
      propagation were observed frequently. These waves always originated from either
      end of the myocyte. 4. The time course of changes in Na(+)-Ca2+ exchange current
      (INaCa) depended on the subcellular properties of the underlying Ca2+ transient
      and on the particular cell geometry. Apparently homogeneous Ca2+ release was
      accompanied by an inward change of INaCa the onset phase of which was fused with
      ICa. Changes in INaCa caused by a Ca2+ wave propagating through the entire cell
      showed a W shape, which could be attributed to differences of the fractional
      surface-to-volume ratio in different cell segments during propagation of the Ca2+
      wavefront. Those waves with limited spreading only activated a small component of
      INaCa. 5. The different subcellular patterns of Ca2+ release signals can be
      explained by spatial inhomogeneities in the positive feedback of the SR. This
      depends on the local SR Ca2+ loading state under the control of the local Ca2+
      influx during activation of ICa. Due to the higher surface-to-volume ratio at the
      two ends of the myocyte, SR loading and therefore the positive feedback in Ca(2+)
      induced Ca2+ release may be higher at the ends, locations where Ca2+ waves are
      preferentially triggered. 6. We conclude that the individual cell geometry may be
      an important determinant of subcellular Ca2+ signalling not only in cardiac
      muscle cells but presumably also in other types of cells that depend on Ca2+
      signalling. In addition, the cell geometry in combination with varying
      subcellular Ca2+ release patterns can greatly affect the time course of Ca(2+)
      activated membrane currents.

PMID- 9003549
TI  - Optical imaging of spatiotemporal patterns of glutamatergic excitation and
      GABAergic inhibition in the guinea-pig auditory cortex in vivo.
AB  - 1. Glutamatergic excitation and gamma-aminobutyric acid (GABA)-ergic inhibition
      in layers II and III of the auditory cortex of anaesthetized guinea-pigs were
      recorded optically using a voltage-sensitive dye RH795 and a 12 x 12 photodiode
      array. 2. After contralateral ear stimulation with pure tones, transient
      excitatory responses followed by inhibitory responses were observed in fields A
      (primary) and DC of the auditory cortex. The area of the excitatory responses was
      sandwiched or surrounded by the areas of the inhibitory responses. 3. Optically
      recorded excitatory responses to pure tones had two components: a component
      sensitive to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D
      aspartate (non-NMDA) receptor antagonist, and a component sensitive to 2-amino-5
      phosphono-valerate (APV), an NMDA receptor antagonist. Application of CNQX (5
      microM) to the auditory cortex suppressed an early, but not a late, phase of the
      excitation; application of APV (100 microM) had the opposite effect. Concomitant
      application of CNQX and bicuculline methiodide (BMI, 4 microM), a GABAA receptor
      antagonist, increased the amplitude of the late phase 4-fold. This enhanced
      response was suppressed by APV. 4. These results indicate that (i) auditory
      cortical excitatory responses are mediated by both non-NMDA and NMDA receptors,
      (ii) inhibition is mediated by GABAA receptors, (ii) the excitatory bands are
      sandwiched or surrounded by GABAA receptor-mediated inhibitory areas and (iv)
      GABAA receptors effectively inhibit the NMDA, but not the non-NMDA, receptor
      mediated excitation.

PMID- 9003548
TI  - Release of Ca2+ is the crucial step for the potentiation of IPSCs in the cultured
      cerebellar Purkinje cells of the rat.
AB  - 1. Spontaneous inhibitory postsynaptic currents (IPSCs) and evoked IPSCs were
      recorded by a whole-cell patch-recording technique from cultured Purkinje cells
      of the rat. The size of spontaneous IPSCs, after a train of depolarizing pulses
      was applied to the Purkinje cells, increased to 163 +/- 6% (mean +/- S.E.M., n =
      7 cells) of the control levels measured before the stimulus train. 2. The
      GABAergic postsynaptic currents were recorded under voltage clamp from the
      synapse formed between two Purkinje cells. These IPSCs increased to 218 +/- 31%
      (n = 4) of control levels after depolarizing stimulation was applied to the
      postsynaptic Purkinje cells. Size-increased IPSCs were observed as long as
      recording continued and the phenomena will be called potentiation in this paper.
      3. Intracellular application of Ruthenium Red (20 microM) did not block the
      potentiation of spontaneous IPSCs induced by the depolarizing stimulus (165 +/-
      9%, n =6), but heparin (2 mg ml-1) partially blocked the potentiation (123 +/-
      10%, n = 6). Heparin applied together with Ruthenium Red (20 microM) blocked
      potentiation completely (96 +/- 5%, n = 8) at concentrations higher than 1 mg ml
      1. 4. Intracellular free calcium concentrations ([Ca2+]i) was monitored as the
      ratio of fura-2 fluorescences excited at 340 and 380 nm. In control cells,
      [Ca2+]i was increased by each depolarizing pulse. When Purkinje cells were
      dialysed with heparin or heparin with Ruthenium Red, the rise in [Ca2+]i was
      suppressed. 5. Bath application of thapsigargin (1 microM) blocked the
      potentiation (99 +/- 2%, n = 4) and suppressed the rise in [Ca2+]i. 6. When 30 mM
      BAPTA was applied intracellularly, a train of depolarizing pulses failed to
      induce potentiation of IPSCs and failed to raise [Ca2+]i. The results from points
      3-6 suggest that the increase in [Ca2+]i, most probably coupled with the release
      from intracellular stores especially from the inositol trisphosphate (IP3)
      sensitive stores, is crucial for the potentiation of IPSCs. 7. Bath application
      of a metabotropic glutamate receptor activator (t-ACPD, 200 microM) increased
      both the amplitude and frequency of spontaneous IPSCs and increased the [Ca2+]i
      slightly in dendrites. The inward current induced by the puff-applied GABA (2
      microM) was increased, after t-ACPD application, to 186 +/- 36% of the control
      level (n = 3). Bath application of quisqualate (2 microM) caused a rapid increase
      in [Ca2+]i in dendrites and in the cell body and increased both the amplitude and
      frequency of spontaneous IPSCs. 8. The bath application of an inhibitor of
      phospholipase C (PLC), U73122 (1 microM), suppressed a rise in [Ca2+]i and
      blocked the potentiation (106 +/- 3%, n = 5). The inactive form, U73343 (1
      microM), did not affect the potentiation (151 +/- 11%, n = 7) or the rise in
      [Ca2+]i. These observations suggest a possible involvement of the mechanism of
      Ca2+ activation of PLC and the IP3-induced Ca2+ release in the induction of IPSC
      potentiation in Purkinje cells.

PMID- 9003550
TI  - Vesicle-associated proteins and calcium in nerve terminals of chick ciliary
      ganglia during development of facilitation.
AB  - 1. The developmental appearance of synaptic vesicle-associated proteins and nerve
      terminal calcium ([Ca2+]i) sequestering processes were determined for the chick
      ciliary ganglia in relation to the maturation of the different phase of increased
      efficacy of transmitter release following nerve impulses. The maturation phases
      studied were from stages 34-35, at the time of synapse formation, to stage 46 at
      hatching. 2. Western blots and immunohistochemical localization indicated that
      synaptotagmin 1 and synapsin IIa were detectable at stages 34-35 and were clearly
      localized at the nerve terminals by stage 37. Syntaxin was clearly localized at
      the nerve terminals at stage 34. 3. The relative size of the postganglionic
      compound action potential, used to measure the transmission efficacy through the
      ganglion, showed that the slope of the relationship between log efficacy and log
      extracellular calcium concentration ([Ca2+]o) in low [Ca2+]o was about 4 by stage
      46. 4. A mature facilitatory mechanism for transmission was not present at stage
      34 and did not emerge until stage 38. A mature augmentation was not present at
      stages 34 or 38 and was not established until stages 41-42. Post-tetanic
      potentiation (PTP) was not present at stage 34; it was evident at stages 37-38
      and only reached maturity by stages 41-42. 5. The time course of calcium changes
      in the nerve terminals following trains of impulses that give rise to
      facilitation, augmentation and PTP was determined for different stages of
      development using the indicator Calcium Green-1 in the nerve terminal. The mature
      time course of the phases of calcium decline in the nerve terminal associated
      with facilitation and augmentation was observed as early as stage 38, whereas
      that of the PTP phase did not mature until after stage 42. 6. These results are
      discussed in terms of the maturation of the vesicle-associated proteins and
      calcium influx into the terminal following trains of impulses that give rise to
      the different components of increased synaptic efficacy.

PMID- 9003551
TI  - Ryanodine-sensitive calcium stores involved in neurotransmitter release from
      sympathetic nerve terminals of the guinea-pig.
AB  - 1. Intracellular and focal extracellular recording techniques were used to study
      neurotransmitter release mechanisms in postganglionic sympathetic nerve terminals
      in the guinea-pig isolated vas deferens. 2. High concentrations of the selective
      N-type calcium channel blocker omega-conotoxin GVIA abolished the release of the
      neurotransmitter ATP evoked by trains of low-frequency stimuli. However, in the
      presence of high concentrations of the blocker, a 'residual release' persisted at
      higher frequencies. 3. Residual release was dependent on calcium entry through a
      pharmacologically distinct voltage-dependent calcium channel. 4. Residual release
      was inhibited by ryanodine in a use- and time-dependent manner and this
      inhibitory effect was potentiated by caffeine. The inhibitory effect of ryanodine
      on residual release was reversed by 4-aminopyridine. 5. These findings indicate
      that calcium-induced calcium released from intraneuronal stores plays an
      important role in action potential-evoked neurotransmitter release mechanisms in
      postganglionic sympathetic nerve terminals.

PMID- 9003552
TI  - The effects of repeated active stretches on tension generation and myoplasmic
      calcium in frog single muscle fibres.
AB  - 1. A series of contractions with stretches (eccentric contractions) beyond the
      optimal length for tension generation (optimum) were shown to induce a shift in
      that optimum in single muscle fibres of frog, as has been previously reported for
      whole muscles. Shifts averaging 0.129 micron (sarcomere)-1 or 6% were found,
      without apparent damage to the fibre. 2. The stiffness of fibres was found to
      fall during a stretch, even though tension was rising. In addition, the isometric
      stiffness fell as a result of a series of eccentric contractions. 3. Calcium
      sensitive fluorescent dyes indicated that such contractions did not reduce the
      amplitude of the intracellular calcium transient, but did increase its duration.
      A rise in resting [Ca2+] was found to accompany damage, but not necessarily the
      shift in optimum. 4. The twitch potentiator nitrate was shown to increase
      myoplasmic [Ca2+] during twitch and tetani, but not to reverse the shift in
      optimum length due to eccentric contractions. Both eccentric contractions and
      twitch potentiation reduced the maximum stimulation rate to which a fibre could
      respond with propagated action potentials. 5. These results exclude reduced
      myoplasmic [Ca2+] as the cause of the shift in optimum length in this
      preparation.

PMID- 9003553
TI  - Coupling between charge movement and pore opening in vertebrate neuronal alpha 1E
      calcium channels.
AB  - 1. Neuronal alpha 1E Ca2+ channels were expressed alone and in combination with
      the beta 2a subunit in Xenopus laevis oocytes. 2. The properties of ionic and
      gating currents of alpha 1E were investigated: ionic currents were measured in 10
      mM external Ba2+; gating currents were isolated in 2 mM external Co2+. 3. Charge
      movement preceded channel opening. The charge movement voltage curve (Q(V))
      preceded the ionic conductance voltage dependence (G(V)) by approximately 20 mV.
      4. Coexpression of alpha 1E with the beta 2a subunit did not modify the voltage
      dependence of charge movement but shifted the G(V) curve to more negative
      potentials. The voltage gap between Q(V) and G(V) curves was reduced by the beta
      2a subunit and both curves overlapped at potentials near 0 mV. 5. The coupling
      efficiency between the charge movement and pore opening was estimated by the
      ration between limiting conductance and maximum charge movement (Gmax/Qmax).
      Coexpression of the beta 2a subunit increased the Gmax/Qmax ratio from 9.2 x
      10(5) +/- 1.4 x 10(5) to 21.9 x 10(5) +/- 2.8 X 10(5) S C-1 for alpha 1E and
      alpha 1E + beta 2a, respectively. 6. We conclude that in the neuronal alpha 1E
      the charge movement is tightly coupled with the pore opening and that the beta 2a
      subunit coexpression further improves this coupling.

PMID- 9003555
TI  - A transferable, beta-naphthoflavone-inducible, hyperpolarizing factor is
      synthesized by native and cultured porcine coronary endothelial cells.
AB  - 1. The vascular endothelium releases a hyperpolarizing factor (endothelium
      derived hyperpolarizing factor, EDHF) tentatively identified as a cytochrome P450
      derived arachidonic acid metabolite. However, there is still controversy
      concerning its transferability and identity. We designed a bioassay system for
      assessing EDHF release in which the membrane potential was recorded in cultured
      vascular smooth muscle cells located downstream from donor endothelial cells. 2.
      Under combined nitric oxide (NO) synthase and cyclo-oxygenase blockade with NG
      nitro-L-arginine (100 mumol l-1) and diclofenac (10 mumol l-1), the superfusate
      from bradykinin (30 mumol l-1)-stimulated, cultured porcine coronary endothelial
      cells induced a distinct hyperpolarization followed by a depolarization. Direct
      application of bradykinin to the smooth muscle cells resulted solely in membrane
      depolarization. Similar results were obtained using bradykinin-stimulated porcine
      coronary arteries as donor. 3. Single-channel current measurements suggest that
      this EDHF-induced hyperpolarization was elicited by the activation of Ca(2+)
      dependent K+ channels. 4. Increasing the transmural pressure within the donor
      segment significantly enhanced the duration, but not the amplitude of the
      hyperpolarization induced by the effluate from bradykinin-stimulated donor
      segments. 5. Inhibition of P450 oxygenase activity with clotrimazole (3 mumol l
      1) or 17-octadecynoic acid (3 mumol l-1) abolished EDHF release from the coronary
      endothelium, while the P450-derived arachidonic acid metabolite, 5,6
      epoxyeicosatrienoic acid, induced a hyperpolarization of detector smooth muscle
      cells almost identical to that induced by EDHF. Moreover, induction of P450
      activity by beta-naphthoflavone (3 mumol l-1, 48 h), significantly increased the
      bradykinin-induced release of EDHF. 6. These findings suggest that the vascular
      endothelium releases a transferable hyperpolarizing factor, chemically distinct
      from NO and prostacyclin, in response to agonists and mechanical stimulation.
      This beta-naphthoflavone-inducible EDHF appears to be a cytochrome P450-derived
      metabolite of arachidonic acid, which elicits hyperpolarization by activation of
      Ca(2+)-dependent K+ channels.

PMID- 9003554
TI  - Calcium channels involved in synaptic transmission at the mature and regenerating
      mouse neuromuscular junction.
AB  - 1. The involvement of the different types of voltage-dependent calcium channels
      (VDCCs) in synaptic transmission at the mature and newly formed mammalian
      neuromuscular junction was studied by evaluating the effects of L-, P/Q- and N
      type VDCC antagonists on transmitter release in normal and reinnervating levator
      auris preparations of adult mice. 2. Nerve-evoked transmitter release was blocked
      by omega-agatoxin IVA (omega-AgaIVA), a P/Q-type VDCC blocker, both in normal and
      reinnervating endplates (100 nM omega-AgaIVA caused > 90% inhibition). The N-type
      VDCC antagonist omega-conotoxin GVIA (omega-CgTX; 1 and 5 microM), as occurs in
      normal preparations, did not significantly affect this type of release during
      reinnervation. Nitrendipine (1-10 microM), an L-type VDCC blocker, strongly
      antagonized release in reinnervating muscles (approximately 40-69% blockade) and
      lacked any effect in normal preparations. 3. In reinnervating muscles,
      spontaneous release was not dependent on Ca2+ entry through either P- or L-type
      VDCCs. Neither 100 nM omega-AgaIVA nor 10 microM nitrendipine affected the
      miniature endplate potential (MEPP) frequency or amplitude. 4. At the newly
      formed endplates, K(+)-evoked release was dependent on Ca2+ entry through VDCCs
      of the P-type family (100 nM omega-AgaIVA reduced approximately 70% of the K(+)
      evoked MEPP frequency). L-type VDCCs were found not to participate in this type
      of release (10 microM nitrendipine lacked any effect). 5. In reinnervating
      muscles, the L-type VDCC blocker, nitrendipine (10 microM), provoked a
      significant increase (approximately 25%) in the latency of the evoked endplate
      potential (EPP). This drug also caused an increase (approximately 0.3 ms) in the
      latency of the presynaptic currents. The P/Q- and Ny-type VDCC blockers did not
      affect the latency of the EPP. 6. These results show that at newly formed mouse
      neuromuscular junctions, as occurs in mature preparations, VDCCs of the P-type
      family play a prominent role in evoked transmitter release whereas N-type
      channels are not involved in this process. In addition, signal conduction and
      transmitter release become highly sensitive to nitrendipine during reinnervation.
      This suggests that L-type VDCCs may play a role in synaptic transmission at the
      immature mammalian neuromuscular junction.

PMID- 9003556
TI  - A slowly activating voltage-dependent K+ current in rat pituitary nerve
      terminals.
AB  - 1. A novel slowly activating voltage-dependent K+ current was observed in
      isolated nerve terminals from rat neurohypophysis using the whole-cell
      configuration of the patch-clamp technique. 2. The activation kinetics of the
      slow current could be fitted assuming Hodgkin--Huxley-type kinetics, an
      exponential, n, of 1.3 and activation time constants decreasing from 4 s at -50
      mV to 0.7s at +40 mV. 3. A positive shift of reversal potential was observed when
      [K+] was increased in the bath solution. The current is carried mainly but not
      exclusively by K+ ions. 4. When intracellular free [Mg2+] was low (approximately
      60 microM), average current density was 74 pA pF-1 at membrane potentials around
      0 mV. In 83% of nerve terminals current amplitude was > 10 pA pF-1. 5. The slow
      current was never observed when the pipette contained 4.6 mM free Mg2+. At a
      physiological level of free Mg2+ (0.5 mM) the average current density was 16 pA
      pF-1. 6. When nerve terminals were analysed after patch-clamp experiments for
      vasopressin content by immunodetection, no difference in current amplitude was
      found between the terminals containing vasopressin and all analysed terminals. 7.
      The voltage dependence of activation was fitted by a Boltzmann equation giving a
      half-activation potential of -37 mV and a slope factor of about 9 mV. 8. Tail
      current deactivation kinetics was biexponential with time constants of 0.12 and
      1.5s. Kinetics was dependent on the duration of the activating pulse. 9. Noise
      analysis of the slow current indicated a single-channel current of 0.33 pA at +6
      mV, corresponding to a single-channel conductance of 4.3 pS. 10. This is the
      first demonstration of a current similar to the slow K+ current, IKs, in a
      neurone, suggesting that a protein similar to the IKs-inducing channel protein
      IsK (minK) may be present in peptidergic nerve terminals. 11. The activation
      properties are consistent with a role of the slow current in inhibition of
      excitability, at least at the level of the nerve terminal.

PMID- 9003557
TI  - Properties and functions of Na(+)-activated K+ channels in the soma of rat
      motoneurones.
AB  - 1. Properties and functions of Na(+)-activated K+ (KNa) channels in the soma of
      motoneurones were studied in spinal cord slices of newborn rat. KNa channels had
      a conductance of 44.8 pS in 5.6 mM external K+ (Ko+)/106 mM internal K+ (Ki+)
      solutions and 139.2 pS in 155 mM Ko+/85 mM Ki+ solutions. KNa channels were
      voltage independent and needed a relatively high [Na+]i to become active (EC50 =
      39.9 mM). Li+ could not substitute for Na+ in activation of KNa channels. The
      channels were predominantly found in the vicinity of cell processes, in the
      regions of most probable accumulation of cytoplasmic Na+. 2. In current-clamp
      experiments, the shape of the single action potential (AP) recorded in Ca(2+)
      free Ringer solution was not changed after substitution of external Na+ with Li+.
      However, 0.4-0.8 s trains of APs were followed by a slow (1-2s) after
      hyperpolarization (sAHP), which reversibly disappeared when external Na+ was
      replaced by Li+. Na(+)-activated sAHP persisted after addition of ouabain and its
      amplitude was even increased in K(+)-free Ringer solution. sAHP disappeared when
      the membrane potential was equal to the K+ equilibrium potential. This indicated
      that sAHP resulted from activation of a Na(+)-dependent K+ conductance, rather
      than from activation of the electrogenic Na(+)-K+ pump. 3. In conclusion, KNa
      channels can play an important role in excitability of motoneurones. KNa channels
      do not make a contribution to the single AP, but they can be activated by a local
      accumulation of internal Na+ during trains of APs. A Na(+)-activated K+
      conductance can reduce membrane excitability and contribute to regulation of AP
      firing in motoneurones.

PMID- 9003558
TI  - Activity and expression of Na(+)-K(+)-ATPase in human placental cytotrophoblast
      cells in culture.
AB  - 1. To determine whether there is a change during differentiation, the activity
      and expression of Na(+)-K(+)-ATPase were studied in mononucleate cytotrophoblast
      cells (18 h culture) and syncytiotrophoblast-like cells (66 h culture). A
      choriocarcinoma-derived cell line (JAr) which, unlike the cytotrophoblast cells,
      divides in culture, was also studied for comparison. 2. Na(+)-K(+)-ATPase
      activity was assessed by measurement of ouabain-sensitive 86Rb+ uptake. Na(+)
      K(+)-ATPase expression was determined by (i) measurement of [3H]ouabain binding
      and (ii) Northern hybridization to measure expression of alpha-1 and beta 1
      subunit mRNA. 3. There was no significant difference in either activity or
      expression of Na(+)-K(+)-ATPase during differentiation of cytotrophoblast cells.
      However, expression of alpha 1- and beta 1-subunit mRNA was significantly lower
      in 66 vs. 18 h cultured cytotrophoblast cells. 4. Both Na(+)-K(+)-ATPase activity
      and [3H]ouabain binding was significantly greater in JAr cells than either
      cytotrophoblast cell groups, although expression of alpha 1- and beta 1-subunit
      mRNA was the same as cytotrophoblast cells cultured for 18 h. 5. It is concluded
      that N(+)-K(+)-ATPase activity and protein expression does not change during
      differentiation of cytotrophoblast cells but that there are changes in expression
      at the transcriptional or post-transcriptional level.

PMID- 9003559
TI  - The source of physiologically stimulated glutamate efflux from the striatum of
      conscious rats.
AB  - 1. Glutamate in the extracellular compartment of the striatum of freely moving
      rats was monitored at 5 min intervals using microdialysis and an enzyme-based
      assay. 2. Basal levels of dialysate glutamate were 3.6 +/- 0.5 microM. Local
      infusion through the dialysis probe of tetrodotoxin (TTX), cadmium chloride or
      magnesium chloride produced no reduction in basal levels of glutamate; with the
      latter two there was, instead, an increase. 3. Neuronal activation stimulated by
      induced grooming was accompanied by an increase in total glutamate efflux of 47.5
      +/- 25.0% above basal level; this increase was not reduced by local infusion of
      TTX. 4. We propose that the TTX-insensitive release of glutamate in response to
      physiological stimulation is derived from glial cells and is a Ca(2+)-dependent
      mechanism triggered by a receptor-mediated release of Ca2+ from internal stores
      that spreads through the network of astrocytes.

PMID- 9003560
TI  - Development of a tonic form of synaptic inhibition in rat cerebellar granule
      cells resulting from persistent activation of GABAA receptors.
AB  - 1. To investigate the origin and functional significance of a recently described
      tonic GABAA receptor-mediated conductance in cerebellar granule cells we have
      made recordings from cells in cerebellar slices from rats of different ages
      (postnatal days P4 to P28). 2. During development there was a dramatic change in
      the properties of GABA-mediated synaptic transmission. The contribution to GABAA
      receptor-mediated charge transfer from the tonic conductance (GGABA), relative to
      that resulting from discrete spontaneous postsynaptic currents (sPSCs), was
      increased from 5% at P7 to 99% at P21. GGABA was reduced by bicuculline,
      tetrodotoxin and by lowering extracellular Ca2+, and was initially present only
      in those cells which exhibited sPSCs. 3. At P7 sPSCs were depolarizing,
      occasionally triggering a single action potential. By P18 the GABA reversal
      potential was shifted close to the resting potential and GGABA produced a
      shunting inhibition. Removal of GGABA by bicuculline increased granule cell
      excitability in response to current injection. 4. This novel tonic inhibition is
      present despite the low number of Golgi cell synapses on individual granule cells
      and appears to result from 'overspill' of synaptically released GABA leading to
      activation of synaptic and extrasynaptic GABAA receptors.

PMID- 9003561
TI  - A novel mechanism of activity-dependent NMDA receptor antagonism describes the
      effect of ifenprodil in rat cultured cortical neurones.
AB  - 1. Ifenprodil is a selective, atypical non-competitive antagonist of NMDA
      receptors that contain the NR2B subunit with an undefined mechanism of action.
      Ifenprodil is neuroprotective in in vivo models of cerebral ischaemia but lacks
      many of the undesirable side-effects associated with NMDA antagonist. 2. Using
      whole-cell voltage-clamp recordings, we have studied the mechanism of inhibition
      of NMDA-evoked currents by ifenprodil in rat cultured cortical neurones in the
      presence of saturating concentrations of glycine. 3. Ifenprodil antagonized NMDA
      receptors in an activity-dependent manner, whilst also increasing the receptor
      affinity for glutamate recognition-site agonists. Ifenprodil inhibition curves
      against 10 and 100 microM NMDA-evoked currents yielded IC50 values of 0.88 and
      0.17 microM, respectively. Thus, the apparent affinity of ifenprodil for the NMDA
      receptor is increased in an NMDA concentration-dependent manner. 4. Currents
      evoked by 0.3 and 1 microM NMDA were potentiated to approximately 200% of control
      levels in the presence of 3 microM ifenprodil. Thus, with increasing
      concentration of NMDA the effect of ifenprodil on NMDA-evoked currents changed
      from one of potentiation to one of increasing inhibition. 5. These results are
      predicted by a reaction scheme in which ifenprodil exhibits a 39- and 50-fold
      higher affinity for the agonist-bound activated and desensitized states of the
      NMDA receptor, respectively, relative to the resting, agonist-unbound state.
      Furthermore, ifenprodil binding to the NMDA receptor results in a 6-fold higher
      affinity for glutamate site agonists. 6. This represents a novel mechanism of
      NMDA receptor antagonism that, together with the subunit selectivity, probably
      contributes to the attractive neuropharmacological profile of this and related
      compounds.

PMID- 9003562
TI  - Functional analysis of a chimeric mammalian peptide transporter derived from the
      intestinal and renal isoforms.
AB  - l. Recently two genes have been identified by expression cloning that encode
      mammalian epithelial peptide transporters capable of translocating di- and
      tripeptides and selected peptidomimetics by stereoselective and rheogenic
      substrate-H+ cotransport. PepT1 from rabbit or human small intestine induces a
      transport activity with high transport capacity but rather low substrate affinity
      when expressed in Xenopus oocytes. In contrast, the renal carrier PepT2 is a high
      affinity-type transporter with a lower maximal transport capacity. In addition,
      both transporters show differences in pH dependence and substrate specificity. 2.
      As a first approach to identify structural components of the transport proteins
      that determine their phenotypical characteristics, we constructed a recombinant
      chimeric peptide transporter (CH1Pep) in which the aminoterminal region (residues
      1-401) is derived from PepT2 whereas the carboxyterminal region (residues 402
      707) starting at the end of transmembrane domain 9 is derived from PepT1.
      Expression of PepT1, PepT2 and CH1Pep in Xenopus oocytes allowed the
      characteristics of the transporters to be determined by flux studies employing a
      radiolabelled dipeptide and by the two-electrode voltage clamp technique. 3. Our
      studies indicate that CH1Pep conserves the characteristics of PepT2 including the
      high affinity for dipeptides and peptidomimetics, the substrate specificity, the
      pH dependence of transport activation and the electrophysiological parameters. We
      conclude that the phenotypical characteristics of the renal peptide transporter
      are determined by its amino-terminal region.

PMID- 9003563
TI  - Mechanical efficiency and fatigue of fast and slow muscles of the mouse.
AB  - 1. In this study, the efficiency of energy conversion in skeletal muscles from
      the mouse was determined before and after a series of contractions that produced
      a moderate level of fatigue. 2. Initial mechanical efficiency was defined as the
      ratio of mechanical power output to the rate of initial enthalpy output. The rate
      of initial enthalpy output was the sum of the power output and rate of initial
      heat output. Heat output was measured using a thermopile with high temporal
      resolution. 3. Experiments were performed in vitro (25 degrees C) using bundles
      of fibres from fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus
      muscles from mice. Muscles were fatigued using a series of thirty isometric
      tetani. Initial mechanical efficiency was determined before and again immediately
      after the fatigue protocol using a series of isovelocity contractions at
      shortening velocities between 0 and the maximum shortening velocity (Vmax).
      Efficiency was determined over the second half of the shortening at each
      velocity. 4. The fatigue protocol significantly reduced maximum isometric force
      Vmax, maximum power output and flattened the force-velocity curve. The magnitude
      of these effects was greater in EDL muscle than soleus muscle. In unfatigued
      muscle, the maximum mechanical efficiency was 0.333 for EDL muscles and 0.425 for
      soleus muscles. In both muscle types, the fatiguing contractions caused maximum
      efficiency to decrease. The magnitude of the decrease was 15% of the pre-fatigue
      value in EDL and 9% in soleus. 5. In a separate series of experiments, the effect
      of the fatigue protocol on the partitioning of energy expenditure between
      crossbridge and non-crossbridge sources was determined. Data from these
      experiments enabled the efficiency of energy conversion by the crossbridges to be
      estimated. It was concluded that the decrease in initial mechanical efficiency
      reflected a decrease in the efficiency of energy conversion by the crossbridges.

PMID- 9003564
TI  - Activation of midlumbar neurones by afferents from anterior hindlimb muscles in
      the cat.
AB  - 1. It has been suggested that a group of interneurones located in the midlumbar
      segments of the spinal cord might play a role in switching from the stance to
      swing phases of the step cycle during locomotion. We have further examined the
      input to these neurones from proprioceptive afferents to test whether the
      connections to these cells are consistent with this role. 2. Electrical
      stimulation of group I and group II afferents in branches of the femoral nerve
      which supply iliopsoas, the major hip flexor muscle, excited a large majority of
      intermediate zone midlumbar interneurones which receive input from quadriceps
      group II afferents. The central latencies and properties of the EPSPs indicate
      that both group I and group II afferents from iliopsoas make monosynaptic
      connections with many midlumbar interneurones. 3. Group II afferents from both
      the ankle flexor tibialis anterior and the digit dorsiflexor extensor digitorum
      longus excited midlumbar interneurones. Similarly, they were also excited by
      group II afferents from both of the two main anatomical divisions of the
      sartorius muscle. 4. The frequent and potent excitation of midlumbar neurones
      from group I and II afferents in iliopsoas suggests that they may be excited at
      the end of the stance phase of the step when these muscles are stretched. This
      possibility is discussed in relation to recent work on the functional control of
      the step cycle.

PMID- 9003565
TI  - Effects of stimulation of phrenic afferents on cervical respiratory interneurones
      and phrenic motoneurones in cats.
AB  - 1. In ten decerebrate, paralysed and ventilated cats, we tested the hypothesis
      that cervical (C5) respiratory interneurones mediate inhibition of phrenic
      motoneurone activity resulting from single shocks to the phrenic nerve. 2.
      Stimulus intensities sufficient to activate all afferents elicited (latency, 4.0
      +/- 0.9 ms, mean +/- S.D.) a graded suppression of ipsilateral, but not
      contralateral (five of seven cats) phrenic nerve activity lasting, in six of
      seven cats, more than 70 ms and interrupted by a brief (approximately 6-18 ms
      duration) excitation at latencies between 7 and 30 ms. 3. In twenty-five
      ipsilateral motoneurones, peristimulus time average of the membrane potentials (
      61 +/- 10 mV) showed no effect in eleven; of the fourteen that responded, ten had
      initial EPSPs (latency, 17.6 +/- 3.0 ms) and four initial IPSPs (latencies, 2.25
      4.3 ms). Only one motoneurone had both. No responses with latencies > 60 ms were
      observed. 4. Peristimulus time averages of extracellular activity of thirty
      ipsilateral interneurones, twenty-five firing in inspiration (I) and five in
      expiration (E), showed diverse responses. The initial response of I interneurones
      was an excitation in eleven, a suppression of activity in nine, and no response
      in five. Latencies of excitations ranged from 2 to 36.5 ms (median, 14 ms) with
      durations ranging from 2 to 7 ms (mean, 4.4 +/- 1.6 ms). Latencies of suppression
      of activity ranged from 2 to 29 ms (median, 10 ms). Two E interneurones were
      excited (latencies, 11 and 15 ms; durations, 3.5 and 2 ms), two inhibited
      (latencies, 2 and 12 ms; durations, > 40 and 17 ms, respectively), and one did
      not respond. 5. In nine interneurones (seven I, two E), peristimulus time
      averages of the membrane potentials (mean, -62 +/- 14 mV) revealed no effect on
      three (all I). Of the six that responded, four (three I) had initial IPSPs, two
      (one I, one E) initial EPSPs. EPSPs had latencies of 11.5 (I interneurone) and 22
      ms (E interneurone); the latencies of the IPSPs were 2.75, 3.20, and 2.3 ms for
      the I interneurones and 15.9 ms for the E interneurone). No responses with
      latencies > 30 ms were observed. 6. The diverse responses of cervical respiratory
      interneurones indicates that they do not mediate the prolonged suppression of
      ipsilateral phrenic activity elicited by stimulation of phrenic afferents. The
      suppression may result from activation of normally quiescent inhibitory
      interneurones or from presynaptic inhibition.

PMID- 9003566
TI  - cGMP-mediated effects on the physiology of bovine and human retinal Muller
      (glial) cells.
AB  - 1. Whole-cell currents of freshly dissociated or cultured Muller cells from human
      and bovine retinas were studied using the perforated-patch and standard whole
      cell recording techniques. 2. We found that internal perfusion of cGMP or
      external exposure to 8-bromo-cGMP activated a calcium permeable, non-selective
      cation current in Muller cells, the principal glial cells of the retina. In
      addition, the activity of calcium-activated potassium channels increased
      markedly. These currents were minimally affected by cAMP. 3. Molecular studies
      using the reverse transcription-polymerase chain reaction demonstrated that human
      muller cells in culture contain transcripts closely related to the rod cyclic
      nucleotide-gated (CNG) channel. 4. Since guanylate cyclase is a known target for
      nitric oxide (NO), we tested the effect of NO donors on Muller cell currents.
      These agents induced currents that were qualitatively similar to those activated
      by cGMP. 5. Our experiments support the idea that the NO-cGMP pathway regulates
      the physiology of Muller cells and may play a role in integrating neuron-glia
      interactions in the retina.

PMID- 9003567
TI  - Invariance of the pattern electroretinogram evoked by psychophysically equivalent
      stimuli in human ageing.
AB  - 1. The aim of this study was to assess the contribution of retinal ganglion cells
      to the decline in contrast sensitivity during human ageing. 2. After
      determination of the appropriate refraction for each subject, younger subjects
      were arranged to be exposed to a display luminance which was suprathreshold by
      the same amount as in older subjects wearing a 4.0 mm diameter artificial pupil
      with a neutral density filter. 3. In fifty-four subjects, aged 20-99 years,
      contrast sensitivities measured in response to phase-reversed grating patterns of
      2, 5 and 8 cycles per degree declined significantly with increasing age at each
      spatial frequency studied. 4. Subjects were made psychophysically equivalent by
      setting the display contrast at x5 and x10 contrast threshold for each subject.
      The pattern electroretinogram (PERG) was recorded with a sterile silver thread
      (DLT) electrode placed in the lower canthus of one eye, with the indifferent
      electrode on the temple and the earth on the forehead. 5. For each contrast
      multiple at each spatial frequency, the PERG implicit time showed no significant
      change with age, indicating equivalence of the response across the age range. 6.
      Control experiments with two young and two elderly subjects established that the
      PERG implicit time decreased appreciably with increasing contrast, over a range
      of x2 to x20 contrast threshold. 7. Since the psychophysically equivalent
      stimulus displays had generated equivalent PERGs in terms of implicit time in
      young and elderly subjects, this was consistent with the equivalence of retinal
      ganglion cell function under these conditions. 8. Adverse changes within the
      retina were therefore inferred to play a major role in the decline in contrast
      sensitivity with age.

PMID- 9003568
TI  - Heat-evoked vasodilatation in human hairy skin: axon reflexes due to low-level
      activity of nociceptive afferents.
AB  - 1. Spreading vasodilatation of the axon reflex type was evoked by contact heat
      stimulation of the hairy skin in the human forearm (13.3 cm2 stimulus area) and
      was detected by laser Doppler flowmetry at 8, 19 and 30 mm distance. 2. From a
      base temperature of 35 degrees C, rapidly rising short heat stimuli (4 degrees C
      s-1, 2 s plateau) elicited vasodilatation at an average threshold of 39.4 degrees
      C. For slowly rising sustained heat stimuli (64 s duration) the average threshold
      was 39.6 degrees C (n.s.) Laser Doppler flowmetry revealed a rapid onset within
      about 4 s, a long duration of several minutes beyond the end of the stimulus, and
      a rapid spread of vasodilatation to remote skin areas. These characteristics are
      typical for vasodilatation by an axon reflex of nociceptive afferents. 3. Axon
      reflex thresholds matched the lower range of C fibre nociceptor heat thresholds.
      Thermal stimuli that were adjusted to elicit about half-maximal phasic responses
      in warm fibres (steps from 30 to 35 degrees C), but were below the range of C
      fibre nociceptor thresholds, did not cause any vasodilatation. 4. Pain thresholds
      were higher than axon reflex thresholds for both rapidly and slowly rising heat
      stimuli and strongly depended on the stimulus pattern (40.1 degrees C for rapidly
      rising stimuli and > 43 degrees C for slowly rising stimuli). This observation is
      consistent with recent reports that the phasic response of nociceptive afferents
      is essential to overcome the summation requirements at central synapses. 5. In
      conclusion, axon reflex vasodilatation in response to heat stimuli in the hairy
      skin of humans is elicited by activation of heat-sensitive nociceptors, even in
      the absence of a conscious perception of heat pain. The dissociation of pain and
      vasodilatation thresholds supports the concept of two operating ranges of primary
      nociceptive afferents. Warm fibres do not contribute to axon reflex
      vasodilatation in the hairy skin of the human forearm. Release of vasoactive
      peptides by nociceptive primary afferents may also contribute to local heat
      evoked vasodilatation at temperatures above 40 degrees C.

PMID- 9003570
TI  - Professional prospects in clinical pharmacology. The British experience.

PMID- 9003569
TI  - Effects of body immersion on postural adjustments to voluntary arm movements in
      humans: role of load receptor input.
AB  - 1. The effect of body immersion on postural adjustments was studied in ten
      healthy subjects. Reaction times, for pushing or pulling a rigid handle, in
      response to a visual stimulus were measured. In addition EMG recordings were
      taken from upper arm and lower leg muscles during three levels of body immersion
      while standing on a platform (immersed to spinal levels: lumbar nerve root 2
      (L2); thoracic nerve root 4 (T4); and cervical nerve root 7 (C7)), while floating
      and while standing or sitting out of water. 2. With increasing levels of body
      immersion there was a near linear reduction in the amplitude of the gastrocnemius
      (GM) EMG activity before (200 ms) the onset of a force signal from pulling, but
      immersion had a significantly weaker effect on the amplitude of the tibialis
      anterior (TA) EMG during pushing movements. There was no significant difference
      in the effect of body immersion on biceps femoris (BF) and rectus femoris (RF).
      Under free-floating conditions postural adjustments did not occur in response to
      pull or push movements. There were no adaptational changes of EMG adjustments
      during successive trials at a given immersion level. 3. Under non-immersed
      conditions reaction times were significantly shorter during sitting than during
      standing. This difference is assumed to be due to the postural adjustments
      required while standing before the onset of a voluntary arm movement. While
      standing, reaction times were significantly longer for pull compared with push
      movements. Under all conditions of body immersion the reaction times remained
      longer compared with the sitting condition, even when no leg muscle EMG
      adjustments were present. 4. It is assumed that the differential effect of body
      immersion on the antagonistic leg muscles is due to the differential neuronal
      control of antagonistic leg muscles with a strong influence from proprioceptive
      input (most probably from load receptors) on the leg extensors. The longer
      reaction times seen during body immersion, where no postural adjustments were
      evident, suggests that a supraspinal command to the leg muscles precedes the
      voluntary arm movement. However, because of the changed/decreased afferent input
      no postural adjustments are generated.

PMID- 9003571
TI  - Combination therapy in the management of HIV infection.

PMID- 9003572
TI  - Adverse drug reactions in HIV positive hospitalized patients. A one-year drug
      surveillance program: study design.

PMID- 9003573
TI  - CPMP note for guidance: clinical trials on the medicinal products in the
      treatment of cardiac failure.

PMID- 9003574
TI  - CPMP note for guidance: clinical investigation of anti-anginal drugs in stable
      angina pectoris.

PMID- 9003575
TI  - Evaluation of quality of life in coronary heart disease.

PMID- 9003576
TI  - Development of new drugs for chronic congestive heart failure and stable angina-
      a clinicians's view.

PMID- 9003577
TI  - Grounds for the integration of pharmacokinetic-pharmacodynamic data.

PMID- 9003578
TI  - Structural modeling: simultaneous pharmacokinetic-pharmacodynamic modeling.

PMID- 9003579
TI  - Alternatives to structural modeling.

PMID- 9003580
TI  - Population-based approach to the assessment of pharmacokinetic-pharmacodynamic
      data.

PMID- 9003581
TI  - Applications of pharmacokinetic/pharmacodynamic research in rational drug
      development.

PMID- 9003582
TI  - Relative expression and stability of a chromosomally integrated and plasmid-borne
      marker gene fusion in environmentally competent bacteria.
AB  - A xylE-iceC transcriptional fusion was created by ligatinga DNA fragment
      harboring the cloned xylE structural gene from the TOL plasmid of Pseudomonas
      putida mt-2 into the cloned iceC gene of Pseudomonas syringae Cit7. This fusion
      construct was integrated into the chromosome of Pseudomonas syringae Cit7 by
      homologous recombination. Both cis-merodiploid strain Cit7m17 and marker exchange
      strain Cit7h69 produced the XylE gene product, catechol2,3-dioxygenase. Strain
      Cit7m17, in which XylE was influenced by transcription initiated by the amp
      promoter on pBR322, exhibited XylE activity in stationary phase at levels about
      45 times higher than strain Cit7h69, permitting detection of 10(7) Cit7m17 cells
      in the spectrophotometric assay and 10(3) cells in HPLC measurements. The
      stability of xylE in both Cit7m17 and Cit7h69 was compared with maintenance of
      xylE in several plasmid-borne constructs in P.aeruginosa, Erwinia herbicola, and
      Escherichia coli. Only the xylE-iceC fusion in the chromosome of Cit7h69 and
      Cit7m17was stable in plate assays over the course of these studies. Even though
      strain Cit7h69 stably expressed xylE, the low level of expression precludes its
      use in direct spectrophotometric or HPLC assays as a means for detecting cells in
      environmental samples. However, expression of xylEin Cit7h69 is sufficient for
      identification of colonies harboring this marker gene which is useful in
      laboratory plate assays, and as a marker gene system for the detection of
      environmentally-competent strains chromosomally taggedwith xylE for use in
      autecological studies.

PMID- 9003583
TI  - Involvement of trihydroxyconjugated bile salts in cholesterol assimilation by
      bifidobacteria.
AB  - To determine the conditions of cholesterol assimilation,various strains of
      Bifidobacterium species were cultured in the presence of cholesterol and bile
      salts. During culturing, Bifidobacterium breve ATCC 15700 assimilates cholesterol
      in the presence of oxgall at pH values lower than 6. This strain was selected to
      study the influence of conjugated (taurocholic acid) and deconjugated (cholic
      acid) bile salts on cholesterol assimilation. B. breve ATCC 15700 assimilated
      cholesterol(up to 51%) when cultures were undertaken in the presence of
      taurocholic acid, whereas less than 13% of the initial amount ofcholesterol was
      measured in the cells in the presence of cholic acid. Cultured in the presence of
      six individual di- or trihydroxyconjugated bile salts, bifidobacteria strains
      assimilated cholesterol. This assimilation appeared to be more important in the
      presence of trihydroxyconjugated bile salts (tauro- and glycocholic acids). It is
      concluded thattrihydroxyconjugated bile salts are involved in the assimilation of
      cholesterol by bifidobacteria.

PMID- 9003584
TI  - Salt-Sensitive and Auxotrophic Mutants of Halomonas elongata and H. meridiana by
      Use of Hydroxylamine Mutagenesis
AB  - The killing action and induced mutagenicity inhydroxylamine (HA)-treated cells of
      two moderately halophilic species of thegenus Halomonas, H. elongata and H.
      meridiana, wereinvestigated. A high sensitivity of H. elongata and especially
      ofH. meridiana to HA was found. The efficiency of the mutagenicityobtained with
      the HA treatment was tested at different salinities. Optimalexperimental
      conditions for HA mutagenesis of these two moderate halophileswere determined. A
      clear, efficient mutagenicity of both H. elongataand H. meridiana after HA
      mutagenesis was achieved. The optimalprocedures yielded a number of useful
      auxotrophic mutants of H.elongata as well as different salt-sensitive mutants of
      H.elongata and H. meridiana for further studies. Some of theselatter mutants
      appeared to be affected in the synthesis of compatiblesolutes.

PMID- 9003586
TI  - Homologous Plasmids from Soil Bacteria Encoding D,L-Halidohydrolases
AB  - We isolated and characterized D,L-halidohydrolases fromfive different soil
      bacteria. Three of these bacterial strains bear plasmidswith sizes of
      approximately 60 kb. Curing and mating experiments indicatedthat these three
      plasmids pFL160, pFL170, and pFL190 encoded a dehalogenase.Owing to their
      biochemical characterization, these halidohydrolases wereclosely related among
      each other and to the DhlIV halidohydrolase, encoded byplasmid pFL40 from
      Alcaligenes xylosoxidans ssp.denitrificans ABIV. Restriction enzyme patterns as
      well asDNA-hybridization experiments with an internal fragment of dhlIVrevealed a
      high degree of homology among each of these four plasmids andtheir dehalogenase
      genes.

PMID- 9003585
TI  - The Anaerobic Fungus Neocallimastix sp. Strain L2: Growthand Production of
      (Hemi)Cellulolytic Enzymes on a Range of CarbohydrateSubstrates
AB  - The anaerobic fungus Neocallimastix sp. strain L2,isolated from the feces of a
      llama, was tested for growth on a range ofsoluble and insoluble carbohydrate
      substrates. The fungus was able to fermentglucose, cellobiose, fructose, lactose,
      maltose, sucrose, soluble starch,inulin, filter paper cellulose, and Avicel. No
      growth was observed onarabinose, galactose, mannose, ribose, xylose, sorbitol,
      pectin, xylan,glycerol, citrate, soya, and wheat bran. The fermentation products
      aftergrowth were hydrogen, formate, acetate, ethanol, and lactate.
      Thefermentation pattern was dependent on the carbon source. In general,
      higherhydrogen production resulted in decreased formation of lactate and
      ethanol.Recovery of the fermented carbon in products at the end of growth ranged
      from50% to 80%. (Hemi)cellulolytic enzyme activities were affectedby the carbon
      source. Highest activities were found in filtrates fromcultures grown on
      cellulose. Growing the fungus on inulin and lactose yieldedthe lowest
      cellulolytic activities. Highest specific activities foravicelase, endoglucanase,
      beta-glucosidase, and xylanase were obtained withAvicel as the substrate for
      growth (0.29, 5.9, 0.57, and 13IU &middot; mg-1 protein, respectively).
      Endoglucanase activitybanding patterns after SDS-PAGE were very similar for all
      substrates. Minordifferences indicated that enzyme activities may in part be the
      result ofsecretion of different sets of isoenzymes.

PMID- 9003587
TI  - Isolation and Characterization of Dehalogenases from2,2-Dichloropropionate
      Degrading Soil Bacteria
AB  - Five bacterial strains were isolated from polluted soilscapable of degrading 2,2
      dichloropropionate. In crude extracts, dehalogenaseactivity against haloacetates
      and longer-chained 2-haloalkanoic acids couldbe detected. Results from activity
      staining indicated that all bacterialstrains expressed a single dehalogenase. In
      further biochemicalcharacterization, two types of D,L-specific 2-haloalkanoic
      acid dehalogenaseswere described, which are different from each other not only in
      molecularweight and electrophoretic mobility, but also in sensitivity towards
      thiolreagents. Dehalogenases of these strains have been shown to be inducible
      andare catalyzing halide hydrolysis with inversion of product configuration.

PMID- 9003589
TI  - Cloning and expression of a Bacillus thuringiensis (L1-2) gene encoding a crystal
      protein active against Glossina morsitans morsitans and Chilo partellus.
AB  - A local isolate of Bacillus thuringiensis,designated L1-2, that is toxic to Chilo
      partellus was found to be toxic to the adult tsetse fly, Glossina morsitans
      morsitans. The delta-endotoxin crystals derived from the isolate gave a major
      protein band with a molecular weight of Mr 130,000-140,000 on denaturing
      polyacrylamide gel electrophoresis. The sequence of the cloned gene was found to
      be similar to that of the B. thuringiensis subsp. kurstaki HD-73 cryIA(c) gene,
      having one amino acid difference at position 148 and four additional DNA
      differences.

PMID- 9003590
TI  - Study of Molecular Karyotypes in Amoeboaphelidium protococcarum,the Endotrophic
      Parasite of Chlorophycean alga Scenedesmus
AB  - On the basis of the pulsed field gel electrophoresis(PFGE) technique, molecular
      karyotypes in Amoeboaphelidiumprotococcarum (the endotrophic parasite of
      chlorophycean algae, whichcombines protozoon- and fungus-type characters) were
      determined. Molecularkaryotypes in the strains X1, X5, and X31, which differ in
      the host range andoriginate from Western, Central, and Eastern Euro-Asia
      respectively,demonstrate the intrageneric polymorphism-from 7 to 13 chDNA bands
      with theestimated molecular size of 0.3-2.2 Mb were resolved, and the genome
      sizewas determined to be between 7.4 and 10.2 Mb. The molecular karyotype
      patternin A. protococcarum is different from that in Protozoa. The low
      gradedistinction in molecular karyotypes between X1 and X5, on one hand, andhigh
      grade distinction between X1/X5 and X31, on the other hand, makes itpossible to
      place X31 in a separate taxon.

PMID- 9003588
TI  - Alkaline serine protease is an exotoxin of Vibrio alginolyticus in kuruma prawn,
      Penaeus japonicus.
AB  - An extracellular lethal toxin produced by Vibrio alginolyticus strain Swy
      originally isolated from diseased kuruma prawn(Penaeus japonicus) was partially
      purified by Fast Protein Liquid Chromatography with hydrophobic interaction
      (Phenyl Sepharose Hig hPerformance) chromatography and gel filtration columns.
      The toxin is an alkaline serine protease, inhibited by phenyl-methylsulfonyl
      fluoride (PMSF),and showed maximal activity at pH 10, having a molecular weight
      of about 33kDa estimated by SDS-PAGE and gel filtration chromatography. In
      addition, the toxin was also completely inhibited by FeCl2 but partially
      inhibited by CaCl2, CuCl2, CoCl2,MnCl2, and ZnCl2, and not inhibited by
      ethylenediaminetetraacetic acid (EDTA), ethylene glycol-bis(beta-amino-ethyl
      ether)N,N,N',N'-tetraacetic acid (EGTA), iodoacetamide, pepstatin A, sodium
      dodecylsulfate (SDS), and N-tosyl-l-phenyl-alanine chloromethyl ketone (TPCK).
      Both the crude extracellular products (ECP) and the partially purified toxin are
      lethal for kuruma prawn at LD50 values of 0.30 and 0.27 microg protein/g body
      weight, respectively. The addition of PMSF completely inhibited the lethal
      toxicity of both the ECP and the partially purified toxin, indicating that this
      serine protease is a lethal factor produced by the bacterium. The 33-kDa protease
      is, therefore, suggested to be a new toxic protease produced by V. alginolyticus
      strain Swy.

PMID- 9003591
TI  - Alginate Encapsulation of the White Rot Fungus Phanerochaetechrysosporium
AB  - In the laboratory, the white rot fungus Phanerochaetechrysosporium degrades
      numerous organic pollutants. Lack of aslow-release delivery system to toxic waste
      sites, for this and other fungi,however, constitutes an important barrier to
      practical implementation. Inthis study, the use of calcium alginate as an
      encapsulant for mycelia wasinvestigated; samples were in the form of pellets 1-3
      mm in diameter. Whenrefrigerated, alginate-embedded mycelia of P. chrysosporium
      wereviable for one year, both with and without nutrient supplementation. At
      roomtemperature, in the absence of nutrient supplementation, viability
      decreasedsharply within 2 months. Addition of sawdust or corncob grits extended
      theviability of alginate-embedded mycelia; nevertheless, after 9 months onlyabout
      20% of the pellets stored at room temperature yielded fungalgrowth. Spores of P.
      chrysosporium, embedded in alginate pelletstogether with corncob grits, gave 75%
      viability after 9 months ofstorage at room temperature. Alginate-embedded mycelia
      were used in Petriplate toxicity tests with 2,4,6-trinitrotoluene (TNT) and gave
      more rapid andreproducible results than tests performed with mycelial plugs.
      Theseexperiments demonstrated the feasibility of encapsulating P.chrysosporium in
      calcium alginate pellets, thus providing a potentialmethod of delivering white
      rot fungi to toxic waste sites, as well as fordeveloping a system of standardized
      toxicity testing in plate assays.

PMID- 9003593
TI  - Antigen detection: the method of choice in comparison with virus isolation and
      serology for laboratory diagnosis of herpes zoster in human immunodeficiency
      virus-infected patients.
AB  - Ninety-two adult human immunodeficiency virus (HIV)-infected patients with
      suspected herpes zoster were included in a study. The clinical diagnosis of
      herpes zoster was verified by examination of blister cell and fluid material or
      serum samples. Antigen detection by a direct immunofluorescence assay with a
      fluorescein isothiocyanate-labelled monoclonal antibody, virus isolation, and
      serologic methods (in-house varicella-zoster virus [VZV] immunoglobulin G [IgG]
      and IgM enzyme-linked immunosorbent assays and the commercial Enzygnost assay)
      were compared. The direct immunofluorescence assay was found to be the most
      sensitive method, diagnosing 85 of 92 infections (92%), while the sensitivity of
      virus isolation was 65% (60 of 92 patients). Despite the use of two different
      serological methods, only 60 of 92 patients (65%) had significant VZV IgG titer
      rises, and only 26 of 92 patients (28%) had detectable VZV IgM. The lack of a VZV
      IgG antibody titer rise was found to correlate with low CD4 counts in peripheral
      blood and high VZV IgG titers in the acute-phase serum sample. The frequency of
      IgM-positive sera was lower than that expected from reports of studies with
      patients without AIDS. This may be related to early antiviral treatment or
      deficient antibody production due to the HIV-related immunosuppression. There was
      no significant difference in CD4 counts between VZV IgM-positive and -negative
      patients.

PMID- 9003592
TI  - Factors affecting reliability and reproducibility of amplification-based DNA
      fingerprinting of representative bacterial pathogens.

PMID- 9003594
TI  - Identification and classification of Oxalobacter formigenes strains by using
      oligonucleotide probes and primers.
AB  - Genomic DNAs of various strains of Oxalobacter formigenes were subjected to
      restriction endonuclease fragment length polymorphism- and PCR-based
      amplification analyses with DNA probes and primers complementary to sequences
      within either the oxc gene, encoding oxalyl coenzyme A (oxalyl-CoA)
      decarboxylase, or the frc gene, encoding formyl-CoA transferase. Oligonucleotide
      probes based on nonconserved sequences of oxc or frc were able to divide O.
      formigenes strains into at least two groups, consistent with the current
      separation of O. formigenes strains into groups I and II on the basis of 16S rRNA
      sequence similarities and lipid content. In contrast, an oligonucleotide probe
      based on the conserved 5' end of oxc appeared to bind all group I and the
      majority of group II strains. PCR amplification of the oxc gene showed even
      greater sensitivity in detecting O. formigenes and provided support for further
      division of the strains into subgroups. In addition, these oligonucleotides
      failed to hybridize to or amplify PCR products from whole fecal DNA isolated from
      fresh stool samples from an individual not colonized with O. formigenes,
      indicating unique specificity. Thus, these DNA analyses permit both detection as
      well as classification of O. formigenes strains.

PMID- 9003595
TI  - Detection of antibodies to respiratory syncytial virus attachment and
      nucleocapsid proteins with recombinant baculovirus-expressed antigens.
AB  - The ability to measure antibodies against individual respiratory syncytial virus
      (RSV) proteins is important in the analysis of immune responses to RSV. We
      expressed the nucleocapsid (N) protein and the group A and B RSV attachment (G)
      proteins from recombinant baculoviruses. The three recombinant RSV proteins were
      used individually in an enzyme-linked immunosorbent assay (ELISA; bac-ELISA for
      results from assays of all three proteins). The bac-ELISA results were compared
      to the results obtained by a whole-virus ELISA (RS-ELISA for results from assays
      of both group A and B viruses). Antibody samples from 113 children were tested.
      The determination of seronegative or seropositive status by the bac-ELISA was
      compared to the same determination by the RS-ELISA; the sensitivity of bac-ELISA
      was 87% (95% confidence interval [CI], 78 to 93%), the specificity was 82% (CI,
      59 to 94%), and the positive and negative predictive values were 95% (CI, 86 to
      98%) and 60% (CI, 41 to 77%), respectively. The group specificity of the G
      protein ELISA was confirmed by testing antibodies from experimentally immunized
      animals. Thus, the bac-ELISA was shown to be comparable to the whole-virus ELISA
      in detecting antibody responses to RSV, while it offered the advantage of
      measuring specific antibody responses to individual RSV proteins.

PMID- 9003596
TI  - Rapid susceptibility testing of Candida albicans by flow cytometry.
AB  - The emerging magnitude of human fungal infections has renewed interest in
      developing rapid and standardized methods for susceptibility testing. We
      demonstrated that susceptibility testing of Candida albicans can be accomplished
      rapidly by using flow cytometry. Test results were available within 8 to 24 h
      after C. albicans isolates were incubated with amphotericin B, itraconazole, and
      flucytosine. This is an improvement of 24 to 60 h in the time to availability of
      susceptibility test results compared to the time to availability of National
      Committee for Clinical Laboratory Standards-recommended broth macrodilution test
      results. In addition, the flow cytometric endpoints, mean channel fluorescence,
      and number of fluorescence-labeled C. albicans cells were easy to interpret for
      greater sensitivity and reliability. Flow cytometry provides a more accurate
      means of obtaining antifungal susceptibility test results.

PMID- 9003597
TI  - Comparison of the Mycobacteria Growth Indicator Tube (MGIT) with radiometric and
      solid culture for recovery of acid-fast bacilli.
AB  - In a multicenter study involving three reference centers for mycobacteria, the
      rate of recovery of acid-fast bacilli (AFB) and the mean time to their detection
      from clinical specimens was determined by using the Mycobacteria Growth Indicator
      Tube (MGIT). These parameters were compared to those assessed by the radiometric
      BACTEC 460 TB system and by cultivation on solid media. Clinical specimens (n =
      1,500) were pretreated with N-acetyl-L-cysteine (NALC)-NaOH. The contamination
      rates for MGITs were 2.0% (center 1), 13.8% (center 2), and 6.1% (center 3). A
      total of 180 mycobacterial isolates were detected (M. tuberculosis complex, n =
      113; nontuberculous mycobacteria [NTM], n = 67). When using a combination of
      liquid and solid media (the current "gold standard" for culture), MGIT plus solid
      media detected 156 (86.7%) of the isolates, whereas BACTEC plus solid media
      recovered 168 (93.3%) of all AFB. Between these two gold standards there was no
      statistically significant difference (P > 0.05). The combination of MGIT plus
      BACTEC detected 171 (95.0%) of all isolates (compared with MGIT plus solid media,
      P < 0.01; compared with BACTEC plus solid media, P > 0.05). Considering the
      efficacies of the different media separately, MGIT was superior to solid media
      (although not significantly; P > 0.05) in detecting AFB but was inferior to the
      BACTEC system (P < 0.01). The mean time to the detection of M. tuberculosis
      complex was 9.9 days with MGIT, 9.7 days with BACTEC, and 20.2 days with solid
      media. NTM needed, on average, 11.9, 13.0, and 22.2 days to appear by the three
      methods, respectively. In conclusion, MGIT proved to be a valuable alternative to
      the radiometric cultivation system.

PMID- 9003598
TI  - Characterization of Aeromonas spp. isolated from humans with diarrhea, from
      healthy controls, and from surface water in Bangladesh.
AB  - Aeromonas isolates from patients with diarrhea in Bangladesh (n = 69), from
      healthy controls (n = 11), and from surface water (n = 40) were analyzed with
      respect to their hybridization groups (HGs) by the aid of fatty acid methyl ester
      (FAME) characterization and DNA fingerprinting by AFLP, biochemical phenotypes
      (Phe-nePlate [PhP] types), and the production of hemolysin and cytotoxin. The aim
      of the investigation was to find out whether certain strains carrying virulence
      factors predominated among patient isolates. According to FAME and/or AFLP
      analysis, most human isolates were allocated to DNA HGs 4 (Aeromonas caviae) and
      1 (A. hydrophila). Most environmental strains were allocated to HG8 (A. veronii
      biogroup sobria) and HG4 (A. caviae), and only one was of HG1. According to PhP
      typing, the diversity among patient isolates was lower than that among other
      strains, and two dominating PhP types (types BD-1 and BD-2) were identified in 29
      and 30% of the patient isolates, respectively. PhP type BD-1 was also common
      among the environmental isolates, whereas PhP type BD-2 was only identified in
      two of the other isolates. Twenty-five of 26 isolates belonging to HG1 were of
      the same PhP type (BD-2), whereas isolates of other common HGs were more diverse
      according to their PhP types. Hemolytic and cytotoxin-producing strains occurred
      more frequently among the environmental isolates than among patient isolates.
      However, the hemolytic and cytotoxic activities among human isolates was strongly
      correlated to the HG1/BD-2 type, which, in addition, showed high cytotoxin titers
      (median values, 1/512 compared to 1/128 for cytotoxin-positive isolates belonging
      to other types). Thus, the HG1/BD-2 type may represent a pathogenic A. hydrophila
      type that is able to produce diarrhea in humans.

PMID- 9003599
TI  - Molecular epidemiology of Mycobacterium tuberculosis strains isolated from
      patients in a human immunodeficiency virus cohort in Switzerland.
AB  - From 1989 to 1995, 46 patients infected with the human immunodeficiency virus
      were diagnosed with tuberculosis at the University Hospital in Zurich. Using the
      IS6110 insertion sequence as a genetic marker, restriction fragment length
      polymorphism analyses were done for 52 Mycobacterium tuberculosis isolates. We
      have found a large degree of IS6110 polymorphism, ranging from 1 to 16 copies.
      For isolates from patients from whom multiple isolates had been available, the
      IS6110 pattern remained virtually stable over a period of up to 4 years, as well
      as during emerging drug resistance. In none of the cases was a reinfection of a
      patient with another strain detected. For isolates from 10 patients we detected
      identical patterns which could be associated with four clusters. In one of these,
      the strains exhibited a low IS6110 copy number (four bands), and the strains were
      further analyzed by hybridizing with (i) the polymorphic GC-rich repetitive
      sequence (PGRS) and (ii) the 36-bp direct-repeat (DR) cluster sequence. One of
      these isolates had a different pattern with the PGRS as well as with the DR
      sequence and could therefore be safely excluded from that cluster. These findings
      point to the importance of applying more than one genetic criterion in the
      molecular biological study of strain relatedness.

PMID- 9003600
TI  - Gordona terrae central nervous system infection in an immunocompetent patient.
AB  - The bacterial genus Gordona includes seven species of mycolic acid-containing
      actinomycetes which are cultured from environmental sources and rarely from
      clinical samples. They have been implicated in primary pulmonary diseases,
      nosocomial wound infections, and central nervous system infections in two
      immunocompromised patients. We isolated Gordona terrae from the cerebrospinal
      fluid sample of an immunocompetent patient with meningitis and multiple brain
      abscesses and detected Gordona terrae DNA in the abscesses. The outcome was good
      at the 4-year follow-up, after prolonged treatment with trimethoprim
      sulfamethoxazole. Phenotypic identification of this isolate was confirmed by
      analysis of the 16S rRNA gene sequence, which shared 100% homology with that of
      G. terrae reference strains. Physicians and clinical microbiologists must be
      aware of the occurrence of Gordona species infection not only among
      immunocompromised patients but among all patients. Accurate identification of
      Gordona species may be accomplished by molecular techniques.

PMID- 9003601
TI  - Biodiversity of Pneumocystis carinii hominis: typing with different DNA regions.
AB  - The purpose of this study was to identify the most useful gene for the detection
      of biodiversity of Pneumocystis carinii hominis isolates and to compare samples
      from French and Italian subjects. We studied 20 bronchoalveolar lavage fluid
      specimens from 20 human immunodeficiency virus-infected patients (10 French and
      10 Italian patients) with Pneumocystis carinii pneumonia by DNA sequencing of the
      thymidylate synthase (TS), 5S rRNA, large-subunit mitochondrial rRNA (mt LSU
      rRNA), and internal transcribed spacer (ITS1 and ITS2) genes. Thirteen of the 20
      sequenced samples had the prototype TS gene sequence. Fourteen of the 20 samples
      showed the prototype sequence of the 5S rRNA gene, and 6 had variant sequences of
      the 5S rRNA gene. The mt LSU rRNA gene was sequenced for 18 of the 20 samples;
      all sequences were different from the prototype sequence and were classified into
      four groups. Thirteen of the 20 ITS1 and ITS2 sequences were analyzed, and all
      the sequences were found to be different from the prototype sequence and were
      classified into 10 groups. The internal transcribed spacer regions thus appear to
      be the most discriminatory region of DNA for analysis of the biodiversity of P.
      carinii hominis isolates.

PMID- 9003602
TI  - Clonal dissemination and colony morphotype variation of vancomycin-resistant
      Enterococcus faecium isolates in metropolitan Detroit, Michigan.
AB  - Thirty-two isolates of vancomycin-resistant Enterococcus faecium (VRE) recovered
      from 25 patients hospitalized at six hospitals in the metropolitan Detroit,
      Mich., area over a 32-month period were examined for relatedness by repetitive
      sequence PCR (rep-PCR). All isolates were shown to carry the vanA gene by PCR.
      The rep-PCR patterns generated from each isolate showed that the first three VRE
      isolates obtained from hospital A between June 1992 and February 1994 were
      distinct strains. Thereafter, all VRE isolates originating from hospital A and
      those collected from five other area hospitals had identical rep-PCR patterns. On
      detailed examination, subcultures of 25 of the 32 VRE isolates produced two
      distinct colony types characterized phenotypically by a rough and a smooth
      appearance, respectively. Both colony types retained the vanA locus and the rep
      PCR pattern of the primary isolate. These data suggest that a single strain of
      VRE with the capacity to produce two colonial variants has been disseminated to
      several Detroit-area hospitals. The clinical significance of the colonial
      morphotypes is unclear.

PMID- 9003603
TI  - A novel Western blot test containing both viral and recombinant proteins for
      anticytomegalovirus immunoglobulin M detection.
AB  - We devised a novel Western blot (WB) test for anti-human cytomegalovirus (HCMV)
      immunoglobulin M (IgM) detection which contains viral structural polypeptides,
      significant portions of recombinant p150 (ppUL32), and a significant portion of
      the most immunogenic nonstructural protein p52 (ppUL44). This new test was
      evaluated in latently infected blood donors, pregnant women, and transplant
      recipients with ongoing HCMV infection and shown to be more sensitive and
      specific than traditional WB and conventional enzyme immunoassay for the
      detection of HCMV-specific IgM.

PMID- 9003604
TI  - Evaluation of a new enzyme immunoassay based on recombinant Rubella virus-like
      particles for detection of immunoglobulin M antibodies to Rubella virus.
AB  - A new enzyme immunoassay for the detection of specific antibodies to rubella
      virus was evaluated at two different sites. This assay, the Roche Cobas Core
      Rubella IgM EIA recomb, uses a recombinant rubella virus-like particle and is
      based upon the immunoglobulin M (IgM) capture principle. It was compared to the
      Abbott IMx Rubella IgM test and to the Sorin ETI-RUBEK-M reverse test. The
      relative clinical specificities were 99.30% for the Roche test, 98.26% for the
      Abbott test, and 100% for the Sorin test. The relative clinical sensitivities
      were 100, 93.87, and 82.65%, respectively. In the case of most primary
      infections, IgM antibodies could be detected immediately at the onset of the
      disease and for up to 7 weeks. In the case of vaccinations, they could be
      detected between 3 and 12 weeks after vaccination.

PMID- 9003605
TI  - Comparison of manual Amplicor PCR, Cobas Amplicor PCR, and LCx assays for
      detection of Chlamydia trachomatis infection in women by using urine specimens.
AB  - We compared the Roche Amplicor PCR, Roche Cobas Amplicor PCR, and Abbott LCx
      assays by using urine specimens for the detection of Chlamydia trachomatis
      infections in a female population. First-catch urine and endocervical swab
      specimens were collected from a total of 442 patients. Urine specimens were
      tested by the manual Roche Amplicor PCR, the automatic Roche Cobas Amplicor PCR,
      and the Abbott LCx assays as instructed by the manufacturers. For the Cobas
      Amplicor PCR, the internal control protocol was used for every specimen to reveal
      the presence of polymerase inhibitors. Cell culture of cervical specimens was
      used as a reference method. Of 442 patients, 50 (11.3%) were confirmed to have
      chlamydial infection. The diagnostic sensitivity and specificity of cell culture
      with cervical swab specimens were 88 and 100%, respectively. With urine specimens
      the sensitivity and specificity for the manual Amplicor PCR assay were 100 and
      99.7%, respectively; those for the automatic Cobas Amplicor PCR assay were 94 and
      99.2%, respectively; and those for the LCx assay were 94 and 100%, respectively.
      Thus, all amplification methods with urine specimens proved to be highly
      sensitive and specific for the detection of C. trachomatis infection in women. No
      statistically significant differences in the test performances could be
      demonstrated for specimens from this population. All three amplification
      techniques with urine specimens proved to be superior to cell culture with
      cervical swab specimens in diagnosing C. trachomatis infections in women.

PMID- 9003606
TI  - Characterization of saccharolytic Bacteroides and Prevotella isolates from
      infected dog and cat bite wounds in humans.
AB  - Saccharolytic, nonpigmented, anaerobic gram-negative rods isolated from infected
      dog and cat bite wounds in humans have been poorly characterized, and most are
      not included in the databases of kits used for anaerobic identification; thus,
      they are problematic for clinical laboratories to identify. Fifty strains
      isolated from such wounds were characterized with commercial kits for preformed
      enzyme detection, carbohydrate fermentation, and other biochemical tests. PCR
      fingerprinting was performed on these strains to further characterize subgroups
      within these species. Bacteroides tectum is a frequent isolate in bite wounds and
      resembles Prevotella bivia in colony morphology and saccharolytic activity,
      except that it grows in 20% bile and hydrolyzes esculin. Profile numbers
      generated by various kits associate B. tectum with P. bivia, Prevotella oralis
      group, or Prevotella melaninogenica. PCR fingerprinting identified at least four
      subgroups and confirmed the heterogeneous nature of this species. Prevotella
      heparinolytica was also frequently isolated from these bite wounds. It produces
      indole and generates a profile number in preformed-enzyme kits that is usually
      associated with Bacteroides uniformis. However, it is bile sensitive and quite
      distinct from the Bacteroides fragilis group of anaerobes. The PCR fingerprint
      profiles generated by strains of P. heparinolytica were very similar to that of
      the type strain and to each other. Prevotella zoogleoformans, occasionally
      isolated from dog and cat bite wounds in humans, resembles P. heparinolytica
      except for a negative indole test. Clinical laboratories should be aware of the
      characteristics of these animal species when identifying isolates from animal
      bite wounds in humans.

PMID- 9003608
TI  - Identification and serotyping of Ornithobacterium rhinotracheale.
AB  - In the present study 443 strains of Ornithobacterium rhinotracheale, a causative
      agent of respiratory disease in fowl, were investigated biochemically and
      serologically. In both ways O. rhinotracheale could be differentiated from other
      gram-negative rods and, more particularly, from the Pasteurella-like bacteria
      potentially pathogenic for fowl. For the biochemical characterization of O.
      rhinotracheale the API 2ONE identification strip proved to be useful, although O.
      rhinotracheale is not included in the API system. Serologically, by using
      monovalent antisera in agar gel precipitation (AGP) tests and enzyme-linked
      immunosorbent assays (ELISAs), seven serotypes (serotypes A to G) of O.
      rhinotracheale could be discriminated. The AGP test was chosen as the preferred
      method to be used for serotyping. Isolates of serotype A were found to be the
      most prevalent, especially in chickens. Isolates from turkeys were more
      heterogeneously divided over the serotypes. Some strains showed cross-reactivity
      between serotypes A, B, and E. Five O. rhinotracheale strains could not be
      serotyped with the available antisera. Relationships between the geographic
      origin and the serotypes were found. By the ELISA the presence of antibodies
      against O. rhinotracheale could be detected in 1-day-old birds as well as in
      birds with clinical signs, and therefore, it might be useful for diagnostic
      purposes.

PMID- 9003607
TI  - Genetic and phenotypic characterization of intestinal spirochetes colonizing
      chickens and allocation of known pathogenic isolates to three distinct genetic
      groups.
AB  - Infection with intestinal spirochetes has recently been recognized as a cause of
      lost production in the poultry industry. Little is known about these organisms,
      so a collection of 56 isolates originating from chickens in commercial flocks in
      Australia, the United States, The Netherlands, and the United Kingdom was
      examined. Strength of beta-hemolysis on blood agar, indole production, API ZYM
      enzyme profiles, and cellular morphology were determined, and multilocus enzyme
      electrophoresis was used to analyze the extent of genetic diversity among the
      isolates. The results were compared with those previously obtained for well
      characterized porcine intestinal spirochetes. The chicken isolates were
      genetically heterogeneous. They were divided into 40 electrophoretic types
      distributed among six diverse genetic groups (groups b to g), with a mean genetic
      diversity of 0.587. Strains in two groups (groups d and e) may represent new
      species of Serpulina, and the groups contained only strains isolated from
      chickens. Three genetic groups contained isolates previously shown to be
      pathogenic for chickens. These corresponded to the proposed species "Serpulina
      intermedius," to an unnamed group (group e), and to Serpulina pilosicoli. Two of
      the chicken isolates (one "S. intermedius" and one S. pilosicoli isolate) were
      strongly beta-hemolytic, two (both "S. intermedius") had an intermediate level of
      beta-hemolysis, and the rest were weakly beta-hemolytic. Fourteen isolates of "S.
      intermedius" produced indole, as did one isolate from group d. Isolates
      identified as S. pilosicoli resembled porcine isolates of this species, having
      four to six periplasmic flagella inserted subterminally in a single row at each
      end of the cell, and had tapered cell ends. All other spirochetes were
      morphologically similar, having seven or more periplasmic flagella and blunt cell
      ends. The identification of three genetic groups containing pathogenic isolates
      provides an opportunity for more detailed epidemiologic studies with these
      pathogens and for the development of improved diagnostic tests.

PMID- 9003609
TI  - Contrast of survey results between state and a cohort of nonstate
      mycobacteriology laboratories: changes in laboratory practices.
AB  - Based on the recommendations of a 1992 conference on tuberculosis, the Centers
      for Disease Control and Prevention (CDC) established programs for upgrading
      mycobacteriology laboratories by providing them with monies and focused training.
      In 1991, state public health laboratories were surveyed to determine the methods
      they were using for primary Mycobacterium tuberculosis testing and their
      turnaround times for reporting testing results. A similar survey of nonstate
      laboratories participating in the National Laboratory Training Network-sponsored,
      M. tuberculosis-focused training programs was conducted from May 1992 to June
      1993. In 1994, follow-up surveys of both the state- and nonstate-laboratory
      cohorts were conducted with the questionnaire from the initial survey plus
      additional questions that asked about interventions and changes occurring in the
      laboratory since the original survey. Although both cohorts showed increases in
      the percentages of laboratories meeting the recommended turnaround times for
      reporting M. tuberculosis testing results and using the recommended rapid methods
      for testing, generally, the increases made by the state laboratories were
      greater. By June 1994, all state laboratories were using a rapid method for M.
      tuberculosis isolate identification compared with 88% of the nonstate
      laboratories. The percentage of laboratories identifying isolates within the
      recommended 21 days also increased more in the group of state laboratories than
      in the group of nonstate laboratories (state laboratories, 22 to 73%; nonstate
      laboratories, 55 to 59%). Responses from the follow-up survey showed large
      differences in the percentages of laboratories that received CDC funding (state
      laboratories, 100%; nonstate laboratories, 6%) and participated in M.
      tuberculosis training (state laboratories, 98%; nonstate laboratories, 45%).
      These results indicate that adequate funding and focused training are critical in
      maintaining state-of-the-art mycobacteriology laboratories.

PMID- 9003610
TI  - Immunoblot assay for serodiagnosis of Helicobacter pylori infections.
AB  - An immunoblot assay for the serological diagnosis of Helicobacter pylori
      infection was evaluated. Serum samples from patients whose gastric biopsy
      specimens were known to be positive or negative for H. pylori on culture were
      used to establish interpretive criteria for the immunoblot assay. A panel of sera
      from patients with diseases other than H. pylori infection and sera from healthy
      blood donors were included to validate these criteria. All sera were initially
      assessed in an enzyme immunoassay (Ge-EIA), based on acid glycine-extracted cell
      surface proteins of H. pylori NCTC 11637. The same antigen extract was used in
      the immunoblot assay. In addition, the Ge-EIA and the immunoblot assay were
      compared with a commercially available EIA (Seradyn, Color Vue Pylori). Bands of
      110/120 kDa and/or two of five low-molecular-mass proteins (26, 29, 30, 31, and
      33 kDa, in any combination) showed a strong correlation with the H. pylori
      culture-positive patients (97.5%) compared to the correlation obtained with the
      EIA results (Ge-EIA, 87.5%; Seradyn EIA, 92.5%), and the antibody responses to
      these proteins were considered specific reactions. In 37 of 40 serum samples from
      culture-negative patients and also in sera from patients with other disorders, a
      moderate antibody reactivity to the medium-size proteins (43 to 66 kDa) was
      observed, and these were considered not valuable for a specific immunoblot assay.
      Among sera from culture-positive patients, 39 of 40 serum samples were defined to
      be immunoblot positive, and from among sera from culture-negative patients, 3 of
      40 serum samples were defined to be immunoblot positive. The use of sera from
      patients with negative cultures for H. pylori as negative controls may decrease
      the sensitivity due to sampling error and false-negative culture results.
      Immunoblot assay-positive results were detected among 10% of sera from patients
      with other diseases, whereas they were detected among 42.5% of sera by the Ge-EIA
      and 47.5% of sera by the Seradyn-EIA. The higher number of EIA-positive sera in
      this group reflects a possible cross-reactivity (false-positive EIA result). Of
      the blood donors, representing asymptomatic but possibly colonized subjects, 24%
      were immunoblot positive. In conclusion, our data indicate that immunoblotting is
      more sensitive as well as more specific than EIA. Moreover, it permits detection
      of antibody responses to specific antigens, e.g., the cytotoxin-associated CagA
      protein, which may have pathological implications.

PMID- 9003611
TI  - Invasive Nattrassia mangiferae infections: case report, literature review, and
      therapeutic and taxonomic appraisal.
AB  - We report on a case of subcutaneous infection of the arm caused by the
      coelomycetous fungus Nattrassia mangiferae (formerly Hendersonula toruloidea) in
      a steroid-dependent diabetic man with chronic obstructive lung disease. The man
      was a resident of Arizona, where the fungus is known to be endemic on Eucalyptus
      camaldulensis and on citrus trees. Diagnosis of fungal infection was made by
      observation of narrow hyphal filaments by histopathology of biopsy specimens and
      isolation of a fast-growing black mold which demonstrated hyphae and
      arthroconidia of varying widths typical of the Scytalidium synanamorph (S.
      dimidiatum). The formation of pycnidia, which at maturity expressed conidia with
      a central median dark band, allowed for the confirmation of the isolate as N.
      mangiferae. Remission of the lesions occurred following intravenous therapy with
      amphotericin B, followed by topical clotrimazole treatment. We use this patient's
      case report as an opportunity to review the literature on cases of deep infection
      caused by Scytalidium species, to evaluate the antifungal susceptibilities of a
      spectrum of Scytalidium isolates, and to review the taxonomy of Scytalidium
      species isolated from human infections.

PMID- 9003613
TI  - A new acid-fast trichrome stain for simultaneous detection of Cryptosporidium
      parvum and microsporidial species in stool specimens.
AB  - The detection in stool specimens of Cryptosporidium parvum and microsporidia, the
      most frequent parasitic pathogens causing diarrhea in AIDS patients, until now
      has depended on two different staining methods. However, since double infections
      occur and minimization of laboratory costs is mandatory, development of a method
      for simultaneous detection of these parasites appeared desirable. We report on a
      new, inexpensive, and easy-to-perform staining procedure to demonstrate both acid
      fast oocysts of C. parvum and other coccidia, as well as microsporidial spores.
      This acid-fast trichrome stain yields results comparable to those obtained by the
      Kinyoun and modified trichrome methods and considerably reduces the time
      necessary for microscopic examination.

PMID- 9003612
TI  - Clinical and molecular study of Corynebacterium diphtheriae systemic infections
      in France. Coryne Study Group.
AB  - Diphtheria is a disease with a long history that almost completely disappeared
      from developed countries. In addition, until 1987, systemic infections involving
      Corynebacterium diphtheriae were rare. However, in 1990, an epidemic occurred in
      Russia. These two circumstances have provided the stimulus to gain insight into
      the situation in France. In fact, between 1987 and 1993, a total of 59 C.
      diphtheriae strains were isolated. Epidemiological data were collected for
      patients from whom 40 strains were isolated from normally sterile sites,
      including 34 from blood cultures, and half of the bacteremic patients developed
      endocarditis. Osteoarticular involvement was noted in 11 of these 40 patients,
      including 5 bacteremic patients. The fatality rate following bacteremia was 36%,
      despite specific antibiotic treatment (beta-lactams and aminoglycosides). The
      mean age of the participants was 38 years, with half of the patients subsisting
      under low socioeconomic conditions and suffering from homelessness or alcoholism.
      Apparently, the skin turned out to be the major route of transmission in this
      reemerging disease. Eighty-eight percent of the isolates belonged to the C.
      diphtheriae biotype mitis. These were found predominantly in the Paris area, and
      most were of the same ribotype. Those isolates originating from the overseas
      territories (Guyana and New Caledonia) belonged to C. diphtheriae biotype gravis.
      No strains were positive for the tox gene by PCR. This study attests to the
      persistent circulation in France of C. diphtheriae in the form of systemic
      infections. The matter is especially significant since these strains are
      nontoxigenic and are of a unique ribotype. The strains are, however, sensitive to
      most antibiotics, although 20% are rifampin resistant.

PMID- 9003614
TI  - Human babesiosis in Taiwan: asymptomatic infection with a Babesia microti-like
      organism in a Taiwanese woman.
AB  - An asymptomatic Babesia infection was confirmed by laboratory diagnoses. The
      intraerythrocytic protozoan (designed TW1) isolated from a 51-year-old Taiwanese
      woman appeared to be morphologically consistent with small-form piroplasm, and
      measurements indicated that it had a body size of 1.5 to 2.5 microm in diameter.
      The typical features of ring, binary, and tetrad forms were observed in Giemsa
      stained thin blood smears. A persistent and low-grade parasitemia was established
      after hamster inoculation. Indirect immunofluorescent-antibody reactivities
      indicate that this strain (TW1) of Babesia was serologically related to, but not
      identical to, the Babesia species (B. microti) that infects rodents. Antibody
      titers in the patient's sera combined with the clinical symptoms suggested that
      the present case was a chronic and subclinical babesial infection. A neighborhood
      human serologic survey indicated that the infection may have been acquired
      accidentally from an infected rodent and localized within the same family.
      Indeed, rodents from areas around the neighborhood were trapped, and a high
      prevalence (83%) of babesial infection was observed. The possible vector
      responsible for the transmission remains to be identified.

PMID- 9003615
TI  - Concordance of Porphyromonas gingivalis colonization in families.
AB  - Periodontitis is a widespread disease that appears to be due to a specific
      bacterial infection. Several species of bacteria have been investigated as
      potential pathogens, and particularly strong evidence links the presence of
      Porphyromonas gingivalis with indicators of periodontitis. Information concerning
      the transmission of P. gingivalis between human contacts may be important in
      determining risk factors for disease and developing preventive strategies. A few
      small studies have provided some evidence of transmission between related
      individuals, but no large-scale study of families that would reflect the typical
      transmission of this pathogen in the population has been reported. The purpose of
      this study was to investigate the transmission of P. gingivalis within randomly
      selected, extended families. The colonization status of 564 members of
      multigeneration families was determined, and the degree of concordance observed
      among members of these families was then compared to that expected to occur based
      on the prevalence of colonization in the population studied. A PCR assay was used
      for detection of P. gingivalis. Concordance in colonization was more frequently
      observed within entire families (P = 0.0000) and for spouses (P < 0.001),
      children and their mothers (P < 0.001), children and their fathers (P < 0.01),
      adults and their mothers (P < 0.005), and siblings (P < 0.05) than would be
      expected if P. gingivalis were randomly distributed in the population studied.
      Results showed that contact with an infected family member substantially
      increased the relative risk of colonization in these intrafamilial pairs. This
      indicates that P. gingivalis is commonly transmitted by contact with an infected
      family member.

PMID- 9003616
TI  - Identification of Serpulina species associated with porcine colitis by
      biochemical analysis and PCR.
AB  - A PCR system for the detection and identification of group IV spirochetes
      (Serpulina pilosicoli) was designed to complement biochemical tests, e.g., the
      hippurate hydrolysis and beta-glucosidase tests, and to verify the accuracy of a
      previously proposed biochemical classification system. The PCR assay was based on
      amplification of a segment of the 16S rRNA gene. Both primers were constructed to
      selectively amplify the 16S rRNA gene of Serpulina pilosicoli. All analyzed
      Serpulina strains exhibiting the capacity to hydrolyze hippurate and lacking beta
      glucosidase activity, including the type strain for spirochetal diarrhea, P43,
      were amplified with the PCR system. All other tested strains, including type and
      field strains of different phenotypes of Serpulina species, as well as Salmonella
      species, Campylobacter species, and Escherichia coli strains, were negative in
      the assay. Among the tested strains were 18 Scottish field isolates originating
      from the mucosae of pigs with colitis. A simple classification scheme, suitable
      for routine classification of porcine intestinal spirochetes, is also presented.
      The scheme is based on hemolysis, indole production, and the hippurate hydrolysis
      test.

PMID- 9003617
TI  - Seroepidemiology of Helicobacter pylori infection in a cohort of children
      monitored from 6 months to 11 years of age.
AB  - A cohort of Swedish children was monitored from 6 months to 11 years of age.
      Immunoglobulin G (IgG) and IgA antibodies to Helicobacter pylori were measured in
      1,857 serum samples, drawn at the ages of 6, 8, 10, 18 months and 2, 4, and 11
      years. Of the 294 children, 40 (13.6%) were found to have been infected at some
      time. However, at 11 years of age, only 6 of 201 (3%) children were seropositive.
      The highest seroprevalence of positive results, 10%, was found at 2 years of age,
      and the highest incidence of 13.3% could be calculated for the period between 18
      months and 2 years of age. There were no confirmed additional cases for children
      between 4 and 11 years of age. Infection with H. pylori thus occurs at an early
      age in a developed country (as well as in developing countries), and spontaneous
      clearance seems to be common.

PMID- 9003618
TI  - Molecular typing of Helicobacter pylori isolates from a multicenter U.S. clinical
      trial by ureC restriction fragment length polymorphism.
AB  - The molecular typing of 81 pretreatment Helicobacter pylori isolates and the
      comparison of 18 pretreatment-posttreatment pairs is described by restriction
      fragment length polymorphism (RFLP) of the ureC gene. The results of our study
      show the extreme genomic diversity of H. pylori and indicate that infection by H.
      pylori in the United States does not appear to be limited to a small number of
      RFLP types.

PMID- 9003619
TI  - Case report: field-acquired subclinical Babesia equi infection confirmed by in
      vitro culture.
AB  - A horse with no prior clinical history of equine piroplasmosis tested negative
      for Babesia caballi and Babesia equi in the complement fixation test before
      importation into the United States from France. After 5 years in residence in the
      United States, the animal tested serologically positive for B. equi by the
      complement fixation test, the immunofluorescent antibody test, and Western blot
      analysis. The carrier status of the horse was confirmed by culture of B. equi
      parasites. In vitro culture offers an efficient and comparatively inexpensive
      method to determine the carrier status of horses suspected of harboring B. equi.

PMID- 9003620
TI  - Performance characteristics of the Gen-Probe Probe Competition Assay used as a
      supplementary test for the Gen-Probe PACE 2 and 2C assays for detection of
      Chlamydia trachomatis.
AB  - The performance characteristics of the Gen-Probe Probe Competition Assay (PCA)
      used in conjunction with the Gen-Probe PACE 2 and 2C direct detection assays for
      Chlamydia trachomatis were examined. Data collected by five public health
      laboratories by using the Gen-Probe PACE 2 were pooled and analyzed. Of 25,081
      endocervical and male urethral specimens tested by the PACE 2 assay, 773 were
      tested by PCA. Of 334 specimens initially positive by the PACE 2 assay with an
      initial PACE 2 result of greater than 2,000 relative light units (RLU), 333
      (99.7%) were positive by PCA while 242 of 339 (71.4%) specimens with an initial
      result between the cutoff and 2,000 RLU were positive by PCA, and 35 of 100 (35%)
      specimens with initial results between 200 RLU and the cutoff were positive by
      PCA. An additional 10,938 specimens were tested by the PACE 2C assay. Of these,
      positive PCA results were obtained for 187 of 188 (99.5%) specimens with initial
      results of greater than 2,000 RLU, 99 of 163 (60.7%) of specimens in the range of
      cutoff to 2,000 RLU, and 12 of 100 (12%) in the range of 200 RLU to the cutoff.
      These results indicate that specimens greater than 2,000 RLU do not require a
      supplemental test and that additional positive results can be obtained by testing
      specimens with an initial result below the cutoff.

PMID- 9003621
TI  - A Mycobacterium tuberculosis IS6110 preferential locus (ipl) for insertion into
      the genome.
AB  - A 267-nucleotide Mycobacterium tuberculosis genomic sequence (ipl, the IS6110
      preferential locus) which can harbor the insertion sequence IS6110 at six
      alternative locations has been identified in some three-quarters of the isolates
      tested. Only one IS6110 copy was observed at this locus in the ipl::IS6110(+)
      containing isolates tested, and all insertions had the same orientation. The
      implications of this finding for IS6110 fingerprint typing methods is discussed
      in this work.

PMID- 9003623
TI  - Epidemiology of group C rotavirus infection in Western New York women of
      childbearing age.
AB  - Umbilical cord serum samples (380), an average of 10 per month for 3 years (1990
      to 1992), were tested by indirect immunofluorescence assay for group C rotavirus
      immunoglobulin G. Thirty percent were positive, suggesting that approximately one
      third of women of childbearing age in western New York have experienced group C
      rotavirus infection.

PMID- 9003622
TI  - Identification and characterization of Serpulina pilosicoli isolates recovered
      from the blood of critically ill patients.
AB  - The phenotypic and genetic characteristics of spirochetes isolated from the blood
      of one U.S. and six French patients with severe clinical disease or impaired
      immunity were examined. All spirochetes were anaerobic, weakly beta-hemolytic,
      positive for hippurate hydrolysis, and negative for beta-glucosidase activity.
      Cell lengths ranged from 4 to 8 microm, and each isolate had between 8 and 12
      periplasmic flagella per cell. These features were consistent with the
      spirochetes' being Serpulina pilosicoli, the agent of intestinal spirochetosis.
      All isolates were positive in a PCR assay amplifying a portion of the S.
      pilosicoli 16S rRNA gene, and they all grouped with fecal isolates of S.
      pilosicoli in multilocus enzyme electrophoresis (MLEE). The blood isolates could
      be differentiated from each other by MLEE, although the U.S. and two French
      isolates were closely related. Apparently S. pilosicoli may translocate from the
      large intestine to establish spirochetemia. The clinical significance of this
      finding remains uncertain and requires further investigation.

PMID- 9003624
TI  - Bacteremia caused by Arcobacter cryaerophilus 1B.
AB  - Arcobacter cryaerophilus group 1B, a gram-negative, curved or helical bacillus
      primarily known as a bovine and porcine pathogen, was isolated from the blood of
      a uremic patient with hematogenous pneumonia. The patient was treated
      successfully with ceftizoxime and tobramycin.

PMID- 9003625
TI  - Mutations in the rpoB gene of Mycobacterium tuberculosis that interfere with PCR
      single-strand conformation polymorphism analysis for rifampin susceptibility
      testing.
AB  - Rifampin susceptibility of 32 rifampin-resistant and 26 rifampin-susceptible
      Mycobacterium tuberculosis strains was analyzed by PCR-single-strand conformation
      polymorphism (SSCP) and DNA sequencing within the 157-bp region of the rpoB gene
      (Ala500 to Val550). Two false-positive PCR-SSCP results were observed among the
      susceptible strains due to the silent mutation Gln513 (CAA-->CAG) and the
      deletion mutation Thr508 and Ser509. Another silent mutation [Leu511 (CTG-
      >CTA)], combined with the mutation Ser531-->Leu, was observed in a resistant
      strain. These results suggest that to rule out false-positive PCR-SSCP results,
      sequencing of the target DNA is required.

PMID- 9003626
TI  - A modified Elek test for detection of toxigenic corynebacteria in the diagnostic
      laboratory.
AB  - The detection of toxigenicity among Corynebacterium diphtheriae and
      Corynebacterium ulcerans strains is the most important test for the
      microbiological diagnosis of diphtheria. Difficulties with current methods, in
      particular the Elek test, are well documented. We therefore describe a modified
      Elek test which provides an accurate result after only 16 h of incubation, in
      contrast to 48 h for the conventional test.

PMID- 9003627
TI  - Trichoderma longibrachiatum infection in a pediatric patient with aplastic
      anemia.
AB  - Trichoderma longibrachiatum infection of the skin in an 11-year-old child with
      severe aplastic anemia and prolonged neutropenia is reported. The patient
      received systemic antifungal therapy and underwent bone marrow transplantation.
      To our knowledge, this is the first description of T. longibrachiatum infection
      in a pediatric patient. It also is the first case successfully treated with
      medical therapy. A review of the literature suggests that Trichoderma spp. are
      recognized as human pathogens with increasing frequency, particularly for
      immunocompromised patients, and should be considered in the differential
      diagnosis of fungal infections in the pediatric population.

PMID- 9003628
TI  - Fulminating bacteremia and pneumonia due to Bacillus cereus.
AB  - We present two cases of rapidly progressing, fatal pneumonia caused by Bacillus
      cereus. These cases are interesting in that B. cereus, even from blood or sputum
      specimens, may often be considered a contaminant and receive inadequate
      attention. Also of interest was the fact that the two patients resided in the
      same area of the state, were welders by trade, and became ill within a few days
      of each other, yet there was no epidemiologic link between them.

PMID- 9003629
TI  - Study of an outbreak of cefoxitin-resistant Klebsiella pneumoniae in a general
      hospital.
AB  - During a 3-month period, six Klebsiella pneumoniae isolates resistant to
      cefoxitin and penicillin-inhibitor combinations were derived from patients in the
      intensive care unit of a hospital in Athens, Greece. Enterobacterial repetitive
      intergenic consensus PCR and pulsed-field gel electrophoresis provided evidence
      of the clonal origin of the isolates. Conventional techniques and ribotyping were
      inadequate in proving that the isolates were related. Resistance was due to a
      plasmidic class C beta-lactamase.

PMID- 9003630
TI  - Use of heat release and an internal RNA standard control in reverse transcription
      PCR detection of Norwalk virus from stool samples.
AB  - Norwalk virus (NV) and the Norwalk-like viruses are important human pathogens
      that cause epidemic acute viral gastroenteritis. Current techniques used to
      recover NV from clinical samples involve multistep viral extraction and elution
      procedures with subsequent viral detection by reverse transcription-PCR (RT-PCR).
      In this study, a simple method using heat to recover viral RNA from 45 stool
      samples was compared to a conventional viral RNA extraction technique, with
      subsequent analysis by RT-PCR. In addition, we used an internal RNA standard for
      the detection of inhibitors present in processed samples. Our results indicate
      that the use of heat to recover NV RNA from stool samples has a sensitivity for
      the detection of NV RNA that is similar to the more labor-intensive, time
      consuming, conventional RNA extraction technique. The use of an RNA internal
      standard permits the detection of inhibitors present in processed samples,
      allowing the identification of false negatives. The standard we developed has the
      advantage of allowing differential detection between wild-type viral RNA and
      standard using internal oligoprobe hybridization.

PMID- 9003631
TI  - Evaluation of a new optical immunoassay for diagnosis of neonatal chlamydial
      conjunctivitis.
AB  - The BioStar OIA Chlamydia test (BioStar, Inc., Boulder, Colo.) is a novel
      immunoassay system that uses changes in reflection of light to directly detect
      chlamydial antigen in clinical specimens. We compared the optical immunoassay
      (OIA) with culture for detecting Chlamydia trachomatis in ocular specimens from
      infants with suspected chlamydial conjunctivitis. We initially performed a
      retrospective evaluation, testing 152 ocular specimens previously collected for
      culture with the OIA. The sensitivity and specificity were 94.2 and 97%,
      respectively. A subsequent prospective study evaluating 37 ocular specimens from
      infants with suspected C. trachomatis conjunctivitis revealed a sensitivity and
      specificity of 100 and 92.6%, respectively.

PMID- 9003632
TI  - Comparison of PCR and hybrid capture methods for detection of human
      papillomavirus in injection drug-using women at high risk of human
      immunodeficiency virus infection.
AB  - We compared Hybrid Capture, a new technique for detection of human
      papillomaviruses (HPV), with a PCR assay based on L1 consensus primers. By both
      methods, the HPV prevalence was higher in human immunodeficiency virus (HIV)
      positive women than in HIV-negative women. PCR had a higher sensitivity (0.89
      versus 0.48) but lower specificity (0.43 versus 0.93) for detection of Pap smear
      abnormalities, compared to Hybrid Capture. The higher intensity of hybridization
      signal by PCR was related to higher estimates of viral load by Hybrid Capture.

PMID- 9003633
TI  - Comparison of QIAamp HCV kit spin columns, silica beads, and phenol-chloroform
      for recovering human immunodeficiency virus type 1 RNA from plasma.
AB  - Human immunodeficiency virus type 1 (HIV-1) pol mutations are responsible for HIV
      1 resistance to current antiretroviral drugs. HIV-1 RNA extraction with QIAamp
      HCV kit spin columns (Qiagen, Chatsworth, Calif.) followed by reverse
      transcription-PCR successfully recovered a 1,008-bp pol fragment from the plasma
      of 31 of 34 HIV-1-infected patients that was suitable for sequencing and
      recombinant-virus studies. The minimum HIV-1 RNA concentration required for gene
      recovery was 30 to 40 copies/ml, which was similar to the minimal HIV-1 RNA
      concentration required when phenol-chloroform or silica beads are used for RNA
      extraction.

PMID- 9003634
TI  - Response of enteric gram-negative bacteria to disks containing 20 micrograms each
      of ampicillin and sulbactam.
AB  - Ampicillin-sulbactam disks containing either 10 microg of each drug or 20 microg
      of each drug were tested against 138 recently, sequentially isolated members of
      the family Enterobacteriaceae. Results obtained with the higher-content disks
      corresponded more closely to the impressions of clinicians.

PMID- 9003636
TI  - Distribution of colonization factor antigens among enterotoxigenic Escherichia
      coli strains isolated from patients with diarrhea in Nepal, Indonesia, Peru, and
      Thailand.
AB  - Samples (1,318) of enterotoxigenic Escherichia coli (ETEC) isolated in 1994-1995
      from children with diarrhea from Nepal, Indonesia, Peru, and Thailand were
      examined for colonization factor antigen (CFA) and coli surface (CS) antigens.
      Fifty-five percent of 361 heat-labile and heat-stable (LT-ST), 14% of 620 LT
      only, and 48% of 337 ST-only ETEC had CFA/CS antigens. LT-ST ETEC strains were
      predominantly in the CFA II group, and ST only strains were in the CFA IV group.
      Additional studies are needed to identify ETEC strains that do not have CFA/CS
      antigens.

PMID- 9003635
TI  - Quantitation of cytomegalovirus (CMV) DNA in leukocytes of human immunodeficiency
      virus-infected subjects with and without CMV disease by using PCR and the SHARP
      Signal Detection System.
AB  - We report the development of a simple and rapid PCR assay for quantitation of the
      cytomegalovirus (CMV) DNA load in polymorphonuclear leukocytes. Using this
      system, a very good correlation was found between a high number of CMV copies in
      the blood and the presence of CMV disease in subjects with AIDS.

PMID- 9003637
TI  - Serologic markers in early stages of African horse sickness virus infection.
AB  - Fifteen horses were experimentally infected with African horse sickness virus
      (AHSV) serotype 4. To learn more about the time course of production and
      specificity of AHSV-specific antibodies, sera were analyzed by immunoblot
      analysis. Only animals that survived for more than 9 days were able to develop a
      humoral immune response detectable by immunoblotting. The earliest serological
      markers corresponded mainly to VP5, VP6, and NS2 and to a lesser extent to VP3,
      NS1, and NS3. Neutralizing antibodies to VP2 were not detected by immunoblotting,
      suggesting that they are mostly conformation dependent. VP7-specific antibodies
      were detected later in infection. These results make NS2 and VP6 the most
      attractive candidates for the rapid diagnosis of the infection.

PMID- 9003683
TI  - Antimicrobial therapy for intraabdominal infection.
AB  - Timely and appropriate antimicrobial therapy is an essential component of the
      management of intraabdominal infection. Over the past three decades, our ability
      to treat these infections optimally has been enhanced by an increased
      understanding of the underlying microbial pathogens, by the development of new
      antimicrobial agents, and by the completion of several well-controlled clinical
      trials that guide treatment. This article provides an overview of the approach to
      antimicrobial therapy in patients with intraabdominal infection. A literature
      review was performed to collect the information used in this article. Data were
      derived from experimental and clinical studies evaluating the microbiology and
      treatment of intraabdominal infections. Evidence from both animal studies and
      clinical trials supports the initiation of empiric antimicrobial therapy directed
      against Escherichia coli and other common members of the family
      Enterobacteriaceae, as well as the anaerobe Bacteroides fragilis. Based on this
      premise, the clinician is faced with a broad selection of possible single agents,
      as well as combinations of agents that fulfill these criteria. The factors
      involved in selecting a specific regimen include consideration of the
      antimicrobial spectrum of various agents, experimental animal studies evaluating
      their efficacy, and, importantly, efficacy in well-designed clinical trials. In
      addition, consideration of safety profiles, pharmacokinetics, and cost of
      specific pharmaceutical agents should be made when selecting a regimen.
      Antimicrobial therapy is an important component of the management of
      intraabdominal infection. The results of well-designed clinical trials evaluating
      various aspects of therapy should serve to guide treatment.

PMID- 9003684
TI  - Soft tissue infections and the diabetic foot.
AB  - Soft tissue infections are classified as local or spreading. Spreading soft
      tissue infections are potentially life-threatening conditions, requiring prompt
      diagnosis and treatment. The information presented is based on a literature
      review and the authors' clinical experience. Diagnosis of soft tissue infections
      is aimed at determining the level of infection (skin, fascia, muscle) and whether
      necrosis is present. The bacteriology of these infections is varied and is of
      secondary importance. Treatment of skin infections that have no dead tissue is
      with antibiotics alone. Infections at the fascial or muscle level and those with
      necrosis at any level require surgical debridement and adjuvant antibiotics. The
      feet of diabetic patients are prone to plantar forefoot ulcers associated with
      tissue destruction and infection. The vast majority are caused by mechanical
      factors. If local immune defenses are adequate, bacterial colonization occurs
      without infection. Most diabetic foot ulcers will respond to relief of pressure,
      which may require total contact casting. Antibiotics and debridement are required
      in infected or deep ulcers, or when the ulcer does not respond to total contact
      casting.

PMID- 9003686
TI  - The importance of antibiotic pharmacokinetics in critical illness.
AB  - Antibiotics are the most commonly used drugs in the surgical patient.
      Pharmacokinetics is the study of processes that result in the delivery of drugs
      to effector sites. Drug absorption, distribution, biotransformation, and
      excretion are the critical elements of drug delivery to effector sites. The
      biologic elimination half-life (t1/2) and the volume of distribution (Vd) are
      terms used to describe the active processes of pharmacokinetics; t1/2 and Vd are
      determined for antibiotics by employing healthy volunteers or minimally ill
      patients. From these data, dosing schedules for each antibiotic are determined.
      This article reviews the literature on the impact of critical illness and sepsis
      on antibiotic pharmacokinetics. The data identify that t1/2 may be reduced in the
      hyperdynamic states of stress and sepsis and that the Vd is expanded. These
      changes mean that currently accepted dosing regimens of antibiotics in critically
      ill patients are inadequate. Subtherapeutic antibiotic concentrations in these
      patients may account for treatment failures and may be of significance in the
      emergence of bacterial resistance.

PMID- 9003687
TI  - Let us shorten antibiotic prophylaxis and therapy in surgery.
AB  - Excessive duration of antibiotics for prophylaxis and treatment of surgical
      infection appears to be the principal reason for "inappropriate" administration
      in current surgical practice. The main factors to blame are the inability of the
      clinician to distinguish between contamination, infection, and inflammation.
      Failure to distinguish between contamination and infection is the reason that
      prophylaxis is unnecessarily carried through into the postoperative phase for
      prolonged periods. Failure to distinguish between infection and inflammation
      misguides surgeons to continue antibiotics for unnecessarily long treatment
      periods. The concept for shortening courses of antibiotic administration is
      supported by a forum of experts. The majority of experts also favored a trend
      away from the use of therapeutic courses of fixed duration, by tailoring the
      duration of administration to the intraoperative findings to shorten treatment
      courses. Specific recommendations are (1) contamination: single dose prophylaxis
      (gastroduodenal peptic perforations operated within 12 hours, traumatic enteric
      perforations operated within 12 hours, peritoneal contamination with bowel
      contents during elective or emergency procedures, early or phlegmonous
      appendicitis, or phlegmonous cholecystitis); (2) resectable infection: 24-hour
      postoperative antibiotics (appendectomy for gangrenous appendicitis,
      cholecystectomy for gangrenous cholecystitis, bowel resection for ischemic or
      strangulated "dead" bowel without frank perforation); (3) advanced infection: 48
      hours to 5 days, based on operative findings and patient's condition (intra
      abdominal infection from diverse sources); (4) severe infection with the source
      not easily controllable: longer administration periods may be necessary (e.g.,
      infected pancreatic necrosis).

PMID- 9003688
TI  - Nosocomial infections and nosocomial pneumonia.
AB  - Nosocomial infections are a major source of revenue loss, morbidity, and even
      mortality to surgical patients. This review presents current issues regarding
      nosocomial infections and nosocomial pneumonias. This study is a literature
      review that presents material on nosocomial infections in general and details
      regarding Clostridium difficile and vancomycin-resistant enterococcus infections.
      Nosocomial infections, including pneumonias, are serious medical complications,
      and prevention by strict adherence to barrier precaution is the most important
      means of protecting the patient from hospital-acquired bacterial flora.

PMID- 9003685
TI  - Diagnosis and treatment of bacteremia and intravascular catheter infections.
AB  - The past decade has witnessed an explosive rise in the rate of bacteremia and
      intravascular catheter infection. Although gram-negative organisms continue to
      account for up to one third of these infections, gram-positive organisms have
      become increasingly prevalent pathogens. Virulent antibiotic-resistant bacterial
      strains have emerged and present a formidable treatment challenge.
      Simultaneously, management of catheter infection has evolved. Although patients
      who develop fungemia, gram-negative bacteremia, or sepsis syndrome are best
      treated by catheter removal in addition to antimicrobial therapy, an increasing
      body of evidence suggests that many gram-positive bacterial catheter infections
      can be treated by use of antimicrobial agents without catheter removal. Advances
      in catheter design and immunotherapy for sepsis syndrome also hold promise.
      Despite these innovations, determining the initial need for catheter placement,
      adherence to meticulous sterile surgical technique during insertion, and
      subsequent fastidious catheter maintenance remain the mainstays of preventing
      these potentially disastrous infections.

PMID- 9003689
TI  - A critical review of antibiotic prophylaxis in severe acute pancreatitis.
AB  - The close association between infection and poor outcome in severe pancreatitis
      has led many investigators to hypothesize that antibiotic prophylaxis might
      reduce infection and thereby reduce mortality. However, despite this possible
      relationship, few studies of good quality have been performed in humans.
      Comprehensive searches using Medline and reviewing relevant published
      bibliographies of English-language human and experimental literature concerning
      acute pancreatitis or pancreatic tissue and antibiotic therapy or
      pharmacokinetics were conducted. Ample experimental evidence indicates that
      aminoglycosides penetrate pancreatic tissue poorly and that penetration of
      penicillins is variable, although the relevance of this is debatable, because
      most tissue that requires debridement in severe pancreatitis is necrotic
      peripancreatic retroperitoneal fat, not the pancreas itself. Although several
      animal studies suggest that antibiotic prophylaxis would be beneficial in severe
      pancreatitis, two recent randomized studies of intravenous antibiotics in humans
      provide conflicting data. There are insufficient data to recommend the use of
      selective digestive decontamination. Some justification exists for the use of
      intravenous antibiotic prophylaxis in severe pancreatitis, but the data are
      insufficient to mandate prophylaxis or to elevate it to the standard of care. If
      chosen, prophylaxis with the combination of a fluoroquinolone plus metronidazole,
      or monotherapy with a carbapenem antibiotic, would be most appropriate. Several
      other questions-including the minimum degree of severity that will benefit, the
      validity of endpoints other than mortality, and reduction of the need for
      surgical drainage-require additional trials.

PMID- 9003691
TI  - The status of anti-infectives in surgery in 1996: a roundtable discussion.

PMID- 9003690
TI  - Timing of treatment for nonneutropenic patients colonized with Candida.
AB  - There has been a continuing evolution of the clinical spectrum of Candida
      infection in nonneutropenic patients. With better understanding of the
      predisposing factors for fungemia in critically ill patients, interest now
      centers on indications for early therapy, prior to the progression of
      colonization to fungemia. Recent prospective trials have identified persistence
      of Candida species in repetitive cultures of various sites as an essential if not
      necessary precursor for fungemia. Treatment for patients requiring prolonged
      intensive-care-unit residence and demonstrating colonization with Candida is
      suggested, based on the frequency with which such patients progress to fungemia.
      The efficacy of such treatment is undocumented, and clinical trials of various
      regimens of polyene or azole antifungals is needed.

PMID- 9003692
TI  - Yeasts: from genetics to biotechnology.
AB  - Yeasts have been known and used in food and alcoholic fermentations ever since
      the Neolithic Age. In more recent times, on the basis of their peculiar features
      and history, yeasts have become very important experimental models in both
      microbiological and genetic research, as well as the main characters in many
      fermentative production processes. In the last 40 years, advances in molecular
      biology and genetic engineering have made possible not only the genetic selection
      of organisms, but also the genetic modification of some of them, especially the
      simplest of them, such as bacteria and yeasts. These discoveries have led to the
      availability of new yeast strains fit to fulfill requests of industrial
      production and fermentation. Moreover, genetically modified and transformed
      yeasts have been constructed that are able to produce large amounts of
      biologically active proteins and enzymes. Thus, recombinant yeasts make it easier
      to produce drugs, biologically active products, diagnostics, and vaccines, by
      inexpensive and relatively simple techniques. Yeasts are going to become more and
      more important in the "biotechnological revolution" by virtue of both their
      features and their very long and safe use in human nutrition and industry.

PMID- 9003693
TI  - Apoptosis in bone marrow cells of mice with different p53 genotypes after gamma
      rays irradiation in vitro.
AB  - Apoptosis is a physiological phenomenon occurring during embryonic development, T
      and B cell maturation, and endocrine-induced atrophy. It can be initiated by
      various agents and has been considered to be related to the expression of the
      oncosuppressor p53 gene. In this review, p53 gene-targeting mice were used to
      study the effect of p53 gene status on the induction of apoptosis in bone marrow
      cells by gamma-ray irradiation. The results showed that homozygous null (p53 -/-)
      murine bone marrow cells were more resistant to the induction of apoptosis by
      radiation than other genotypes (heterozygous, p53 +/- and wild type, p53 +/+).
      The percentage of apoptotic cells in p53 +/+ mice was about three times that in
      p53 -/- mice at 4 hr after 6 Gy gamma-irradiation, and the analysis of the
      apoptosis-characteristic DNA ladder further supported these findings. We found
      that the homozygous null mice also can undergo apoptosis after irradiation. This
      suggested that there is another independent apoptotic p53 gene mechanism in
      irradiated murine bone marrow cells. Thus, in murine bone marrow cells, both p53
      gene-dependent and -independent apoptosis occurred after irradiation. In our
      previous work, an increase in survival of hemopoietic progenitor cells after
      irradiation in vitro in p53 gene deletion mice was observed. This increase is
      closely related to the inhibition of apoptosis in bone marrow cells in p53 gene
      deletion mice.

PMID- 9003695
TI  - Cigarette smoking causes biochemical changes in blood that are suggestive of
      oxidative stress: a case-control study.
AB  - Cigarette smoking has been shown to be a major risk factor for cardiovascular
      disease, lung cancer, and respiratory diseases. Due to its high content of
      oxidants, the cigarette smoke is bound to cause a prooxidant/antioxidant
      imbalance in the blood plasma and tissues of smokers. The study groups were
      selected from an apparently healthy population living in urban areas, comprising
      200 subjects aged 18 to 80 years, half of whom were smokers. In smokers aged 18
      to 45 years, the changes of the plasma prooxidant parameters (i.e., lipid
      peroxides, leukocyte activation, and the antioxidant ones [thiol concentration,
      total antioxidant capacity]) were not significantly different from those of the
      age-matched controls, whereas in the 46 to 80 age group they were. In smokers,
      both antioxidant erythrocyte enzymes, glutathione peroxidase (GSH-Px) and
      superoxide dismutase (SOD), exhibited increased activity in the 18 to 45 age
      group and decreased activity in the 46 to 80 age group. The differences in enzyme
      activity between the smoking and nonsmoking groups were highly significant for
      SOD in all ages, whereas for GSH-Px the difference in activity was significant
      only in the case of older smokers. These findings would suggest that a process of
      adaptation takes place in younger smokers, in whom the antioxidant systems are
      able to counteract the oxidant factors, while in older smokers this process is no
      longer occurring and the plasma and tissues are under permanent oxidative stress.
      Our results clearly demonstrated that a prooxidant/antioxidant imbalance exists
      in the blood of smokers, and the determination of leukocytes stimulation index
      may be a useful and simple way of assessing the oxidative stress status of these
      individuals. A hypothesis regarding a possible mechanism linking cigarette
      smoking to the development of coronary heart disease is presented.

PMID- 9003694
TI  - Somatic cell mutation in workers occupationally exposed to mercury vapors.
AB  - Somatic cell mutation in human peripheral lymphocytes is one of the tools used
      recently in the biological monitoring of the work environment. The scope of this
      review was to test whether biomonitoring methods are sensitive to the presence of
      mercury (Hg) in the body. We used the following techniques: micronucleus
      frequency (MN), sister chromatid exchanges (SCE), and hypoxanthine guanine
      phosphoribosyl transferase (HGPRT) assay in human lymphocytes. A total number of
      30 male workers exposed to Hg vapors in chloralkali industry had been selected
      and compared with 30 control subjects. The concentration of mercury in urine
      (HgU) was used as a biological index of exposure. The exposed group showed higher
      levels of MN (32.0 +/- 1.7), SCE (7.3 +/- 0.2),and HGPRT mutations (0.94 +/-
      0.01) then the nonexposed controls. We recommend the introduction of somatic cell
      mutation analysis in the periodic medical examination of workers exposed to Hg
      vapors.

PMID- 9003696
TI  - Cigarette smoke increases cholesterol oxidation and lipid peroxidation of human
      low-density lipoprotein and decreases its binding to the hepatic receptor in
      vitro.
AB  - Low-density lipoprotein (LDL) was exposed to six puffs of cigarette smoke (CS)
      filtered through a glass wool filter and then incubated for 6 or 20 h at 37
      degrees C. Control LDL was similarly treated but exposed to air. In cigarette
      smoke-treated LDL (CS-LDL), compositional changes of the lipid fraction were most
      detectable after 20 h incubation. These changes included a decrease of
      polyunsaturated fatty acids (PUFA), slight degradation of
      phosphatidylethanolamine (PE) and phosphatidylcholine (PC) to their
      lysophospholipid lysoPE and lyso-PC, elevation of oxidized cholesterol content as
      well as thiobarbituric acid reacting substance (TBARS), indicating an oxidative
      effect of CS on LDL. CS-LDL also showed higher anodic electrophoretic mobility
      and crosslinking of its apoprotein by nondisulfide bonds. The binding affinity of
      CS-LDL to liver membrane receptor was much lower than control LDL as measured by
      the calcium-dependent binding of LDL-gold conjugate to the solubilized membrane
      protein dot blotted onto nitrocellulose strips. Our results indicate that CS
      induces changes in LDL, making it more atherogenic and cytotoxic.

PMID- 9003697
TI  - Association of herpes simplex virus type-I and human papilloma virus with
      carcinoma of the oral cavity and oropharynx.
AB  - This study consists of 56 carcinoma cases of the oral cavity and oropharynx, 56
      controls matched for age, sex, and habits, and 100 other controls proportionate
      to the population of Karachi. Biopsy material of the carcinoma cases and oral
      smears of the two control groups were negative for HSVI and HPV with peroxidase
      antiperoxidase staining. The Enzyme Immunosorbent assay (EIA) of sera revealed
      significantly high levels of anti HSV-I IgG and IgM antibodies in carcinoma cases
      (96.43% and 25.00%, respectively) when compared with matched controls (73.21% and
      3.5%, respectively).

PMID- 9003698
TI  - Magnesium: its role in cellular functions--a review.
AB  - Magnesium has been identified as an important element in cellular functions, and
      its abnormalities have far-reaching effects in pathology. We reviewed its effects
      in the cell cycle, its physiological role, nutritional aspects, toxicity,
      mutagenesis, and tumorigenesis.

PMID- 9003699
TI  - Incorporation of bromodeoxyuridine (BrdU) in the bronchiolar-alveolar regions of
      the lungs following two inhalation exposures to chrysotile asbestos in strain A/J
      mice.
AB  - We have been studying early fibroproliferative events in the lungs of rodents
      exposed to aerosols of asbestos fibers. In the experiments presented here,
      incorporation of bromodeoxyuridine (BrdU) in the bronchiolar/alveolar (B/A)
      regions of the lungs in mice was assessed following two consecutive exposures to
      chrysotile asbestos. Six to 8-week-old male strain A/J mice, a strain with a high
      spontaneous incidence of B/A tumors, were exposed to inhaled asbestos fibers for
      two consecutive days (3 hours/day). A group of mice was also given an
      intraperitoneal injection of urethane, a known lung carcinogen in A/J mice, 48 h
      after initial inhalation exposure to asbestos. The groups of mice exposed to
      asbestos had significantly (p <0.05) increased incorporation of BrdU in the
      nuclei of epithelial and interstitial cells in the B/A regions of the lung at 48
      h, 72 h, and 2 weeks after initial exposure. By 1 month, the labeling indices in
      mice exposed to asbestos were not statistically significantly different from the
      controls; however, in the regions of the first alveolar duct bifurcations (ALDB),
      the primary site of initial asbestos deposition, there continued to be detectable
      labeling of the epithelial and interstitial cells. Because of considerable
      variability from duct to duct, there were no statistically significant
      differences between the asbestos-exposed mice and control groups at 3 months. We
      conclude that in A/J mice the initial proliferative response observed in the B/A
      regions of the lung after two 3-h inhalation exposures to asbestos is
      significantly prolonged through 2 weeks post-exposure. In addition, there was
      measurable labeling above control values in the epithelial and interstitial cells
      of the first alveolar duct bifurcations up to 3 months after exposure. Urethane
      had no apparent effect on the incorporation of BrdU into any cells of the B/A
      regions of the lung when administered after inhalation exposure to asbestos.
      Furthermore, although the A/J strain is highly susceptible to lung tumor
      formation, the unexposed control A/J mice showed no spontaneous increases in cell
      proliferation.

PMID- 9003700
TI  - Temporal expression and cellular distribution of pulmonary fibronectin gene
      induction following exposure to an emission source particle.
AB  - This study examines the ability of an emission source particle, residual oil fly
      ash (ROFA), to influence pulmonary fibronectin (Fn) gene expression. Fn is an
      extracellular matrix (ECM) protein involved in a variety of cellular functions,
      including inflammation, cell proliferation, and fibrosis. Temporal expression and
      spatial distribution of Fn gene induction were assessed by in situ hybridization
      in rat lung during acute phase of lung injury occurring 6 to 72 h following
      intratracheal instillation of ROFA. Fn mRNA was not detected in rat lungs treated
      with either saline or at 6 h after ROFA treatment. However, Fn mRNA was induced
      in airway epithelial cells 24 h after ROFA instillation. Histopathology showed
      peribronchial inflammation and focal edema. Diffuse inflammation in alveolar
      region with limited expression of Fn mRNA was evident 48 h after ROFA exposure,
      occurring mainly in proliferating epithelial cells. Extensive Fn mRNA expression
      was seen in proliferating fibroblasts and in hyperplastic epithelial cells within
      incipient fibrotic lesions 72 h after exposure, while the intensity of expression
      in the airway epithelial cells was decreased. Therefore, Fn mRNA induction was
      associated with inflammatory and incipient fibrotic lesions, indicating its
      possible involvement in airway hyperreactivity and initiation of fibrogenesis.

PMID- 9003701
TI  - Breast cancer in pregnant and lactating women.
AB  - Between 1988 and 1991, we treated 595 women with breast cancer in the Breast
      Disease Section of the Cancer Research Foundation of Pakistan. We report here on
      61 patients who were pregnant or lactating. Most patients presented at a late
      stage of disease because of ignorance, social taboos, or fear of hospitalization
      and operation. The largest diameter of the breast mass at presentation was 15 cm.
      Lymph nodes were involved in 70.5% of cases. Multiparity, young marriages,
      malnutrition, and unhygienic conditions are ripe in the rural environment of
      Pakistan. No oral contraceptives are used. Modern and conventional methods of
      treatment did not increase the survival rate of these cancer patients.

PMID- 9003702
TI  - Electronic mailing lists.

PMID- 9003704
TI  - Historical dose reconstruction project: estimating the population at risk.
AB  - This paper discusses methods used to estimate the size and location of the
      populations that lived around the Feed Materials Production Center near Ross,
      Ohio, from 1950 through 1990. This information will support an historical dose
      reconstruction for environmental exposures to radionuclides from this facility
      that is currently being done by the Centers for Disease Control and Prevention
      through a contract with Radiological Assessments Corporation. Available sources
      of data include (1) the U.S. Census, Ohio Township data; (2) the U.S. Census,
      Ohio Township block data; and (3) U.S. Geological Survey topographical maps that
      show structures. A distribution of age and sex is estimated that, together with
      population estimates, will provide information needed to estimate collective dose
      rates over time and to examine the feasibility of studying the relationship
      between exposure to radionuclides released from the Feed Materials Production
      Center and adverse health outcomes.

PMID- 9003703
TI  - Predicted versus measured tritium oxide concentrations at the Savannah River
      Site.
AB  - Measured tritium oxide concentrations in air at various offsite locations are
      compared with concentrations predicted by three computer codes that are utilized
      at the Savannah River Site to estimate doses to maximally exposed offsite
      individuals. Annual average concentrations calculated by the computer models were
      compared with measured average concentrations taken from monitoring data
      collected over the last 10 y. The computer programs used for the comparison are
      AXAIRQ, MAXIGASP, and CAP88. The 10-y averaged ratios of predicted-to-measured
      tritium oxide air concentrations using AXAIRQ, MAXIGASP, and CAP88 are 1.89+/
      0.56, 1.70+/-0.48, and 1.40+/-0.39, respectively. The difference in ratios is
      primarily due to different wind speed averages used within each of the models.
      These results show exceptional agreement, considering Gaussian plume models
      typically over predict annual average air concentrations by a factor of two to
      four.

PMID- 9003705
TI  - Risk ranking by perception.
AB  - The study of people's perception and acceptability of risk is important in
      understanding the public reaction to technology and its environmental and health
      impact. The perception of risk depends on several factors, including early
      experiences, education, controllability of the risk, the type of consequence, and
      the type of person(s) who makes the judgment. This paper reviews some of the main
      factors influencing people's perception and acceptability of risk. Knowledge
      about which factors influence the perception of risk may enhance the
      understanding of different points of view brought into risk controversies,
      improve risk communication, and facilitate policy making. Results from a risk
      ranking by perception survey conducted in Ghana are also presented.

PMID- 9003706
TI  - Estimated cost of person-Sv exposure.
AB  - The present paper summarizes work performed under contract to the Department of
      Energy and reported separately. This paper covers efforts to define a cost per
      person-Sv by determining a value for a societal life and coupling the result with
      the probability of death due to radiation exposure. The value of a societal life
      was estimated by examining wrongful death awards and settlements, amounts taken
      out in life insurance, amounts spent in the last year of life for the critically
      ill, lifetime earnings and investments, and other approaches and values found in
      related literature. The values of a societal life ranged from $600,000 to
      $7,000,000, with a value of $4,000,000 considered by the authors as a
      conservative average in terms of 1990 U.S. dollars. The associated costs per
      person-Sv thus determined were found to range from $18,000 per person-Sv to
      $630,000 per person-Sv ($180 per person-rem to $6,300 per person-rem), with a
      value of $200,000 per person-Sv ($2,000 per person-rem) taken as a conservative
      average.

PMID- 9003708
TI  - Induced current and SAR distributions for a worker model exposed to an RF
      dielectric heater under simulated workplace conditions.
AB  - We have used the finite-difference time-domain method to calculate the
      distributions of absorbed energy for a 1.34 x 1.34 x 1.4 cm resolution
      anatomically based model of the human body for exposure to leakage
      electromagnetic fields of a radiofrequency dielectric heater operating at 40.68
      MHz. To simulate workplace conditions, the dielectric heater is assumed to be
      placed in a screen room and different operator postures, such as standing or
      sitting on a wooden or metal stool with hands on sides or extended toward the
      radiofrequency heater, are considered. To obviate the problem of having to model
      a fairly large volume of the screen room of assumed dimensions 2.13 x 3.05 x 2.13
      m, we have used a uniform finer grid of points for the finite-difference time
      domain method for the closely coupled region consisting of the front region of
      the heater and the human model, while a newly developed expanding-grid finite
      difference time-domain formulation is used elsewhere. This results in a saving of
      both the memory and computation times by almost a factor of four. The average
      rates of energy absorption are given for the whole body, selected parts of the
      body, and various organs. As expected, the foot currents and the rates of energy
      absorption are higher with the screen room for sitting postures where the upper
      parts of the body are in higher electromagnetic fields, and for hands extended
      toward the heater.

PMID- 9003707
TI  - Circulatory kinetics of intravenously injected 238Pu(IV) citrate and 14C-CaNa3
      DTPA in mice: comparison with rat, dog, and reference man.
AB  - New ligands for in vivo chelation of Pu(IV) are being synthesized and evaluated
      in mice for efficacy and toxicity. Biokinetic studies of the new ligands, CaNa3
      DTPA, and Pu(IV) are major components of those investigations. Young adult female
      mice were injected intravenously (iv) with 3H-inulin, 14C-CaNa3-DTPA, or
      238Pu(IV) citrate to provide baseline data for plasma clearance, tissue uptake,
      and excretion rates and to determine the dilution volume (VOD) and renal
      clearance rate (RC) of filterable substances. Published plasma clearance data for
      iv-injected 14C-CaNa3-DTPA and Pu(IV) citrate in Reference Man, dog, and rat were
      collected. Based on combined data for 3H-inulin and 14C-CaNa3-DTPA, VOD = 17% of
      body weight and RC = 18 mL kg(-1) min(-1) for mice. Retention of 14C-CaNa3-DTPA
      in the four species is proportional to body weight and inversely proportional to
      RC: Integrals of the retention of 14C-CaNa3-DTPA from R(t) = 1.0 to R(t) = 0.05
      are 108, 43, 28, and 10 DF min, respectively, for Reference Man, dog, rat, and
      mouse. Clearances of iv-injected Pu(IV) citrate from plasma are in the same
      order: The plasma curve integrals from injection to 1440 min are 840, 640, 280,
      and 67 DF min, respectively, for Reference Man, dog, rat, and mouse. In mice, a
      large fraction of newly injected Pu(IV) is rapidly transferred to the
      interstitial water of bulk soft tissue (excluding liver and kidneys), from which
      it is cleared at the same rate as from the plasma. Rapid plasma clearance, escape
      into interstitial water (22%ID at 20 min), significant early urinary excretion
      (8%ID in 12 h), and prompt deposition in liver and skeleton (complete in 12 h)
      are evidence of inefficient binding to plasma protein (mainly transferrin) of
      newly injected Pu(IV) in mice. Conversely, slow plasma clearance, little early
      urinary excretion, and delayed deposition in liver and skeleton reflect more
      efficient binding by transferrin of newly injected Pu(IV) in Reference Man and
      dog. Pharmacokinetic parameters (effective dosage, effective concentration) of
      CaNa3-DTPA, alone or combined with plasma Pu(IV) integrals, yielded only
      qualitative predictions of the relative efficacies of CaNa3-DTPA therapy in four
      species. The need for improved models of Pu(IV) and ligand biokinetics and the
      suitability of the three animals for predicting chelation therapy outcomes in
      humans are discussed.

PMID- 9003709
TI  - Radiocesium contamination in a submediterranean semi-natural ecosystem following
      the Chernobyl accident: measurements and models.
AB  - Radiocesium dynamics in a Quercus conferta Kit ecosystem in Northern Greece have
      been extensively studied over the years 1993-1995. Radiocesium distribution in
      the different parts of the ecosystem was measured. A total 137Cs inventory of
      243+/-66 MBq ha(-1) due to the Chernobyl accident was measured in all parts of
      the ecosystem. Almost 90% of this inventory is still in the upper layers of the
      soil and the forest floor. In particular 13.4% is in the forest floor, 52.6% in
      the Ah horizon, and 23.4% in the upper 5 cm of the soil. Only 2.2% of this
      inventory is in the above ground biomass. The mean total 137Cs deposited on the
      forest floor from the above ground biomass is 0.18 MBq ha(-1) y(-1). Cesium
      leaching from the forest floor is negligible. The radiocesium distribution in
      soil is fixed and in equilibrium, at least since 1993. Most of radiocesium is not
      available for migration. Cesium migration in soil was modeled by a) an
      "equivalent diffusion" model with different initial conditions and b) a
      "compartment" model derived from a diffusion-advection model. A compartment model
      for the contamination of living biomass is proposed. The total absorbed dose rate
      in air as well as the contribution due to 137Cs from the Chernobyl accident was
      determined inside the forest, by in-situ gamma spectrometry.

PMID- 9003710
TI  - Fast measurements of transmission of erythema effective irradiance through
      clothing fabrics.
AB  - For efficiently measuring ultraviolet transmission through clothing materials for
      a large number of samples, an automated measuring system with a broad-band method
      has been built and calibrated against a spectroradiometer based instrument. The
      apparatus can be used to test 60 samples in 25 min. A selection of clothing
      materials of known composition, weave, color and state have been tested, using
      the broad band method and the automated measuring system together with a solar
      ultraviolet simulator. Variations of about eleven times for different weave
      structure, about two times in the ultraviolet transmittance for different colors,
      and about 20 times for some stretched samples were observed. For wet conditions,
      an increment in ultraviolet transmittance for cotton and lycra materials and a
      decrement for polyester and polyester(65%)/cotton(35%) were also observed.

PMID- 9003711
TI  - A compartmental model of water radon contamination in the human body.
AB  - A multicompartmental model is developed to simulate the biokinetics in the human
      body following the ingestion of an inert gas. It was assumed that 100% of the
      radon ingested appears in the stomach, from which it is transported through the
      body to different organs via the blood stream. Each of these organs absorbs and
      releases radon differently, and, amongst all, the fat retains radon for the
      longest time. To test the model, the information on elimination rates of 222Rn in
      expired breath was obtained from other experiments done at the University of
      Maine. The data included male and female participants with a wide range of ages
      and physical activity levels. The radiation doses in the different organs and
      tissues were computed. As was expected, the stomach sustained the maximum dose.
      In this study, the highest stomach dose to any volunteer was evaluated as 115 mSv
      y(-1).

PMID- 9003712
TI  - Residential radon and lung cancer in Sweden: risk analysis accounting for random
      error in the exposure assessment.
AB  - A large epidemiologic study on residential radon exposure and lung cancer has
      been conducted in Sweden. An attempt is now made to quantify the impact of random
      error in the exposure assessment on the risk estimate for lung cancer in this
      study. The study included 1,360 lung cancer cases, diagnosed from 1980 to 1984,
      and 2,847 population controls. Radon measurements were performed in 8,992
      dwellings occupied by the study subjects some time since 1947. Questionnaires
      provided information on smoking and other risk factors. Imprecision in the
      retrospective exposure assessment for radon was estimated from a Monte Carlo
      technique modeling Swedish conditions. Adjusted risk estimates were obtained from
      regression analyses based on expected values for true time-weighted average
      residential radon concentration (TWA), conditional on observed TWA. Without
      adjustment for random error in the TWA estimates, the linear excess relative risk
      coefficient was 0.10 per 100 Bq m(-3), but an excess relative risk of about 0.15
      to 0.20 per 100 Bq m(-3) was suggested following adjustment. The potentially
      significant consequences of errors in the retrospective radon exposure assessment
      should be taken into consideration in the risk estimation as well as in
      comparisons of results of different studies and in future pooled analyses.

PMID- 9003713
TI  - Efficient adsorption of waterborne short-lived radon decay products by glass
      fiber filters.
AB  - Glass fiber filters of a certain brand were found to be very efficient (retention
      > 95%) for adsorption of short-lived radon decay products during filtration of
      water. Carrier-free samples are obtained in a convenient geometry for efficient
      gross beta counting. Adsorption of "hot atoms" is not disturbed by the presence
      of "cold" lead ions. Approximate radioactive equilibrium between radon and its
      short-lived decay products may or may not exist in water at the source, but does
      exist after 3 h in PET bottles. These bottles are shown to be gas-tight for
      radon. Calibration of activity concentration in Bq L(-1) (radon gas concentration
      approximately equilibrium equivalent radon concentration) was performed by
      several standard procedures. Limit of detection is 2 Bq L(-1) within 10 min
      (total time) or 10 Bq L(-1) within 5 min for a net signal of 5 times standard
      deviation.

PMID- 9003714
TI  - When is a lower limit of detection low enough?
AB  - In cleanup operations and environmental surveillance efforts, a level of concern
      usually specifies a concentration limit for a particular radionuclide above which
      some action may be warranted. It is critical that the analytical method selected
      for measurements has a detection limit well below the action level. This is to
      guarantee that the technique used provides precise assessment at the level of
      concern. Sample analysis made with good precision is one of the major steps for
      obtaining quality data that allow a sound decision on whether the nuclide
      concentration is in compliance. This paper examines how the magnitude of the
      detection limit of an analysis method affects the precision of a measurement at
      the action level. With the established relationship, the detection limit that
      would achieve a pre-set precision for measurements at a level of concern can be
      quantitatively determined. The desired detection capability thus serves as a
      guide for selecting the appropriate measurement system.

PMID- 9003715
TI  - Data quality objectives for surface-soil cleanup operation using in situ gamma
      spectrometry for concentration measurements.
AB  - In situ gamma spectrometry is an efficient method for monitoring the progress of
      cleanup activities for radioactive contaminants in surface soil and for
      evaluating the attainment of cleanup standards. However, desired data precision
      and accuracy must be specified for such a detection system prior to the operation
      to ensure that the level of uncertainty associated with the concentration
      measurements is acceptable. A method for developing data quality objectives is
      described in this paper for in situ gamma spectrometry to achieve numerical goals
      for data precision and accuracy for cleanup operations. Concentration measurement
      for a radionuclide at its cleanup level must have a precision commensurate with
      the importance of cleanup decisions. The 95% lower limit of detection of the
      system is suggested to be about one tenth the expected system response at the
      cleanup level. The count time required to achieve the preferred 95% lower limit
      of detection, and hence the desired precision, can then be determined. The
      accuracy error arises from the overall calibration factor, which relates the
      detector responses (e.g., count rate) to physical quantities of interest (e.g.,
      radionuclide soil concentration). The major source of error for the calibration
      factor using in situ gamma spectrometry is the misidentification of the type of
      the depth profile of radionuclide concentration in soil. If surrogate
      radionuclides are used, such as 241Am for plutonium, the variation in the
      concentration ratio would be another significant source of error. Soil sampling
      programs performed prior to a cleanup operation will greatly reduce the accuracy
      error for an in situ detection system, and the analysis of system errors may
      determine the degree of sampling required. The planning of such a program is
      discussed in the study. Uncertainty analysis using a Latin Hypercube sampling
      technique for the calibration factor is also demonstrated. The quantitative
      result of the uncertainty analysis is useful for determining a nuclide's maximum
      peak count rate using gamma spectrum that ensures the attainment of the cleanup
      standard for that nuclide with a pre-specified confidence level (e.g., 95%). The
      cleanup operation of 239,240Pu in surface soil in the safety shot areas at the
      Nevada Test Site serves as an example to illustrate the data quality objectives
      development.

PMID- 9003717
TI  - Issues in establishing an aerosol radiological baseline for the waste isolation
      pilot plant near Carlsbad, New Mexico.
AB  - The Department of Energy has constructed a deep geologic repository for defense
      transuranic waste disposal. The Waste Isolation Pilot Plant, located in
      Southeastern New Mexico, is slated to receive transuranic waste by truck delivery
      beginning in 1998. The Environmental Evaluation Group (EEG) provides an
      independent evaluation of the impact on the health and environment in New Mexico
      of the WIPP project. Since 1985, the EEG has operated a network of air monitoring
      sites around WIPP and in nearby communities. The radionuclide concentration data
      from these air samples have been assembled into a useful baseline data base after
      resolution of a number of methodological and quality assurance issues.
      Investigation thresholds for the principal radionuclides have been calculated
      from combined data collected from several sites. These action levels will provide
      a critical quantitative basis for decisions of whether future airborne
      radionuclide measurements are attributable to accidental releases.

PMID- 9003716
TI  - Removable surface contamination at a biomedical research institution.
AB  - A rigorous, unannounced, campus-wide survey for removable surface contamination
      was performed at our institution. Wipe samples (n = 1,090) were collected from a
      variety of standardized locations in 45 large biomedical research laboratories
      that routinely use kBq-MBq (microCi-mCi) amounts of 3H, 14C, 32P, 35S, 51Cr, and
      125I. The results showed a log-normal distribution for contamination, with about
      90% of all samples below ten times background. Although working surfaces and
      equipment used in these laboratories can become contaminated with radioactive
      materials, especially by transfer from soiled gloves, the magnitude of the
      contamination is very small and typically restricted to surfaces, instruments,
      and equipment that are directly handled in the course of experimental work and
      which can be reasonably anticipated to be contaminated. These data suggest that
      contamination is not a significant problem in biomedical research laboratories at
      this institution and that the best protection from workplace contamination
      appears to continue to be the use of well-reviewed standard operating procedures
      and good work practices.

PMID- 9003718
TI  - Chest wall thickness measurements: the alternative approach extended for 241Am.
AB  - The Human Monitoring Laboratory has extended the technique of determining the
      chest wall thickness of an individual using information from the spectrum
      produced by internally deposited radionuclides. The technique has been
      investigated both theoretically and practically using germanium detectors and the
      Lawrence Livermore Torso Phantom. The phantom was used with a lung set containing
      homogeneously distributed 241Am. Chest wall thicknesses were varied by using a
      series of muscle equivalent overlay plates that gave a range of 1.6 cm to 3.9 cm
      thickness. It was found that a 3-cm chest wall thickness can be estimated to
      within 18%. Using a spectral addition technique 1 kBq was estimated to be the
      "practical" lower limit of activity for this method.

PMID- 9003720
TI  - Evaluation of aperture efficiency of a radiofrequency electric field strength
      meter antenna.
AB  - With present-day rapid increases in the applications of radiofrequency microwave
      radiation in research, medicine, defense, communications, and industry, it has
      become necessary to have simple inexpensive portable radiofrequency microwave
      field strength meters for health and safety surveys around operating equipment.
      This paper presents the results of a study conducted at Trombay calibrating grid
      to evaluate the receiving aperture efficiency of the 1-m long antenna of a simple
      narrow band electric field strength meter, with frequency response centered
      around 27.12 MHz. An aperture efficiency of 0.47 with a coefficient of variation
      of +/-3.46% is considered adequate for field use.

PMID- 9003719
TI  - Computer model generated density correction factors for gamma spectroscopy
      counting.
AB  - Using the calibration curve of a single reference source to infer activity levels
      in samples of different bulk density and/or elemental composition may yield
      inaccurate results by a gamma spectroscopy system. These inaccuracies are
      magnified when counting low energy photons, which interact primarily through the
      photoelectric effect. There have been numerous methods described to empirically
      derive density correction factors for various samples. An alternate solution is
      to theoretically derive density correction factors using a computer model. The
      computer model generated density correction factors for material such as sand,
      ilmenite, and polyester are in close agreement with published empirically derived
      density correction factors for these same materials.

PMID- 9003721
TI  - NESHAP risk assessment.

PMID- 9003722
TI  - Duration of transient hyperechoic images of white matter in very-low-birthweight
      infants: a proposed classification.
AB  - To enhance the comparability of research results, a uniform terminology is
      proposed for the description of the duration of transient hyperechoic images of
      white matter seen on cranial ultrasound scans of very-low-birthweight infants.
      The term 'flare' should be restricted to any hyperechoic image that resolves
      completely without any abnormality in its place. A flare should be termed 'brief'
      if it resolves within 6 days of its appearance, 'intermediate' if it disappears
      between 7 and 13 days after onset, and 'prolonged' if it disappears on day 14 or
      later.

PMID- 9003723
TI  - Hand function in low-risk preterm infants: its relation to muscle power
      regulation.
AB  - Some preterm infants show a discrepancy in muscle power often recognisable as
      hyperextension of trunk and shoulders. Even if there is no evident pathology
      involved, the hyperextension influences later hand function. In this study we
      assessed a group of healthy infants (N=51) at the age of 39 weeks: 32 were born
      preterm (and corrected for gestational age) and 19 were born at term. Both
      quantitative and qualitative measures of hand function were obtained. It was
      found that the preterm infants scored significantly lower scores in both
      assessments for hand function. Moreover, a significant correlation was found
      between the quality of hand function at the age of 39 weeks and hyperextension of
      the trunk at 18 weeks. Hyperextension of the trunk at 18 weeks had a high
      predictive value for poor hand function at 39 weeks and thus should hold
      implications for clinical and therapeutic management.

PMID- 9003724
TI  - Using motor milestones as a multistep process to screen preterm infants for
      cerebral palsy.
AB  - Pediatricians often informally use motor milestones to screen infant motor
      development, and one advantage is that they can be used during sequential office
      visits, as a multistep screening process. In this study we evaluated six motor
      milestones (roll prone to supine, roll supine to prone, sit with support, sit
      without support, crawl and cruise) as a multistep process in screening for
      cerebral palsy in 173 high-risk preterm infants (<33 weeks gestational age) who
      had been followed with sequential developmental assessments for at least 18
      months. At the 18 to 24 month evaluation, 31 (18%) had cerebral palsy. We found
      that using the motor milestones as serial screening tests for cerebral palsy was
      more effective in terms of positive predictive value than any individual
      milestone alone. Limited community resources can be more efficiently used if
      preterm infants with delays in more than four motor milestones are referred for
      further evaluation and early intervention services.

PMID- 9003725
TI  - Childhood traumatic brain injury: neuropsychological status at the time of
      hospital discharge.
AB  - The present study examined the status at the time of hospital discharge of 22
      children who had sustained moderate to severe closed head injuries. Despite an
      average length of stay of 46 days, on average the children performed
      significantly below normal on cognitive, memory, and motor tests. The children
      who did the worst were those who sustained their injuries riding in a vehicle, as
      opposed to being hit by a vehicle while walking or riding a bicycle. No reliable
      associations were found between neuroimaging data and cognitive measures;
      however, children whose scans showed more diffuse severe injury (e.g. white
      matter hemorrhages) performed more poorly than those who did not. Of further
      importance were detailed morphometric analyses of tissue quantity and ventricular
      volume that showed significantly increased ventricle to brain ratios (VBR) over a
      3 to 4 week period following injury.

PMID- 9003726
TI  - Clinical characteristics and long-term outcome of migraine with aura in children
      and adolescents.
AB  - A population of 45 young subjects, 16 males and 29 females, affected by migraine
      with aura were studied prospectively. The mean follow-up was 7 years 6 months.
      The clinical characteristics and modifications during migraine aura attacks were
      evaluated. The aura propagated slowly with a pattern corresponding to a cortical
      pathway in the posteroanterior direction in 71% of the series, and was visual
      alone in 40%. Analysis of the relation between the course, and therefore
      prognosis, and the aura type showed that headache has a better prognosis when
      symptoms continue to be only visual. The International Headache Society (IHS)
      classification subdivides migraine with aura into six categories based on the
      duration of symptoms and the clinical characteristics (hemiplegic, basilar). Our
      results suggest that subjects with only visual aura should be considered
      separately, possibly as a seventh category, because they may have a more
      favourable prognosis.

PMID- 9003728
TI  - Internal rotation gait: a compensatory mechanism to restore abduction capacity
      decreased by bone deformity.
AB  - Children with excessive femoral anteversion frequently walk with abnormal
      internal rotation of the hip. The authors hypothesized that excessive anteversion
      decreases the abduction moment arm of the gluteus medius and that this moment arm
      is restored with internal rotation; hence internal rotation may be a compensatory
      mechanism to preserve abduction capacity. To test this hypothesis a three
      dimensional computer model of an adult lower limb was developed to determine how
      changes in femoral anteversion angle, neck-shaft angle, and hip internal rotation
      angle affect the abduction moment arm of the gluteus medius. Analysis of the
      model revealed that anteversion and valgus deformities of the femur can decrease
      the abduction moment arm of the gluteus medius substantially. In particular,
      increasing the anteversion angle of the model by 30 to 40 degrees caused a 40 to
      50% decrease in the abduction moment arm of the gluteus medius - enough to impair
      walking. Internal rotation of the hip by 30 degrees restored the abduction moment
      arm of the gluteus medius to within 5% of the moment arm of the model in its
      normal, undeformed state. These results support the authors' hypothesis and are
      consistent with the theory that internal rotation may be a compensatory mechanism
      adopted by children with femoral deformities to achieve the abduction moment arm
      needed for walking.

PMID- 9003727
TI  - The contribution of risk factors to the effect of early otitis media with
      effusion on later language, reading, and spelling.
AB  - A cohort of 946 children who were screened for otitis media with effusion (OME)
      from the ages of 2 to 4 were studied for language, reading, and spelling at 7
      years of age. The effects of OME in combination with single risk factors and with
      increasing numbers of risk factors were investigated. An interaction with an
      additional risk factor was found only for gender and OME, with boys' spelling
      influenced negatively by a history of OME. OME in combination with preterm birth
      and low birthweight also appears to put children at risk for later language and
      educational problems. Although a negative linear relation between the number of
      risk factors and later functioning was found, it is suggested that OME, even when
      combined with a number of other risk factors, produces only minor effects on
      later language, reading, and spelling.

PMID- 9003729
TI  - Equinus deformity in cerebral palsy: recurrence after tendo Achillis lengthening.
AB  - Twenty-seven patients with cerebral palsy (CP) were recalled and studied in
      detail 2 to 9 years post tendo Achillis lengthening (TAL). The recurrence rate of
      equinus deformity was 22.2%. Multiple clinical characteristics and follow-up
      examination findings were analyzed to determine their relation to recurrence. The
      recurrence group had a significantly (P<0.05) smaller preoperative popliteal
      angle, a greater popliteal angle at follow-up, and a greater change in popliteal
      angle from preoperative to follow-up than the non-recurrence group. This
      indicated that increasing hamstring contracture was the major factor influencing
      recurrence. Spasticity of tibialis posterior and leg-length discrepancy may be
      related factors as well.

PMID- 9003730
TI  - Dopa-responsive childhood dystonia: a forme fruste with writer's cramp, triggered
      by exercise.
AB  - An 11-year-old girl was evaluated for walking difficulties and fatigue at the end
      of the day in the last 2 years. Handwriting was also difficult with 'cramps'
      after a short time of writing. Neurological examination was normal most of the
      time but in the evening and after exercise, an abnormal walking posture and rare
      dystonic movements of the foot could sometimes be seen. The mother was found to
      have mild parkinsonism and is asymptomatic on L-dopa. In the daughter, all
      symptoms and signs disappeared on L-dopa, but returned when the drug was
      withdrawn. The changes on- and off-treatment were documented with videofilms and
      computerized analysis of writing samples. The situation has been stable during a
      5-year follow-up. We draw attention to this 'forme fruste' of dopa-sensitive
      childhood dystonia which becomes manifest with exercise and which can easily go
      unrecognized. We also discuss and illustrate the methods used for the analysis of
      writing.

PMID- 9003731
TI  - Current awareness: spotlight on consciousness. The 1996 Ronnie Mac Keith lecture.

PMID- 9003732
TI  - Pyridoxine dependency: an update.

PMID- 9003733
TI  - Nutritional management of the disabled child: the role of percutaneous endoscopic
      gastrostomy.

PMID- 9003734
TI  - Antibacterial peptides and the outer membranes of gram-negative bacilli.

PMID- 9003735
TI  - Zoonoses. Introduction.

PMID- 9003736
TI  - Zoonoses: a personal perspective on the Jennerian principle of cross-protective
      immunity.

PMID- 9003738
TI  - Hantavirus infections.

PMID- 9003737
TI  - Food- and milk-borne zoonotic infections.

PMID- 9003739
TI  - Poxvirus zoonoses.

PMID- 9003740
TI  - Zoonotic protozoa.

PMID- 9003741
TI  - Hydatid disease.

PMID- 9003742
TI  - Development of antibiotic resistance: a vet's tale.

PMID- 9003743
TI  - Application of the Mast resistotyping scheme to Campylobacter jejuni and C. coli.
AB  - The Mast resistotyping scheme was assessed with 228 strains of Campylobacter
      jejuni and C. coli from enteric infections in man and from a diverse selection of
      other sources (livestock, chickens and river water). Most (153 of 158) C. jejuni
      examined were of the three most common Penner (heat stable, HS) serotypes, HS1,
      HS2 and HS4 complex. Fourteen resistotypes were identified in the 158 strains of
      C. jejuni and 16 in the 70 isolates of C. coli. The predominant codes were 00
      (44% of C. jejuni; 33% of C. coli) and 40 (21% of both species). The scheme was
      simple to use but reproducibility and interpretation of sensitivity zones-
      notably for fluorouracil, triphenyltetrazolium chloride and metronidazole--was
      occasionally problematic. Overall, resistotypes did not correlate with Penner HS
      serotypes or with three key genomic markers (ribotype, PFGE macrorestriction-type
      and fla-type). Although resistotyping offers a rapid means for distinguishing
      between some strains of C. jejuni and C. coli, discrimination for common
      resistotypes can be achieved only in combination with other typing methods.

PMID- 9003744
TI  - Media and tests to simplify the recognition and identification of members of the
      Proteeae.
AB  - Several important and diverse human pathogens are found in the tribe Proteeae. By
      identifying and concentrating on key biochemical reactions, it has been possible
      to devise six simple media that permit the identification of all the important
      members of the tribe with ease, speed and accuracy. This was confirmed by
      optional additional confirmatory media and tests.

PMID- 9003745
TI  - Rapid identification by specific PCR of coagulase-negative staphylococcal species
      important in hospital infection.
AB  - Polymerase chain reaction (PCR) identification assays were designed for eight
      major species of coagulase-negative staphylococci (CNS) on the basis of three
      variable regions found in the 16S rRNA gene. The PCR assays were tested with 41
      staphylococcal strains representing the diversity of staphylococci defined by
      classical biotyping schemes. Each PCR result was compared with species-specific
      polymorphism in and around the 16S rRNA gene (i.e., 16S ribotype) and the
      phenotypic identification of the strain in a miniaturised biochemical test
      gallery (bioMerieux ATB 32 Staph). Twenty-six of the 41 strains were identified
      by PCR as belonging to one of the eight species for which primers had been
      designed and none of the remaining strains was misidentified. For 22 of the 26
      strains there was complete agreement between the PCR identification, 16S ribotype
      and ATB identification. For the remaining four strains there was agreement
      between PCR identification and 16S ribotype. Two National Collection of Type
      Culture strains were re-assigned to different species and 10 previously
      unassigned strains were formally speciated for the first time. These PCR assays
      are suitable for rapid and definitive speciation of CNS.

PMID- 9003746
TI  - Prevalence of single and multiple infection with human papillomaviruses in
      various grades of cervical neoplasia.
AB  - Evaluation of human papillomavirus (HPV) diversity in various grades of cervical
      lesions is helpful for understanding the characteristics of HPV infection in the
      pathogenesis of cervical neoplasia. A total of 227 women with normal cervices (n
      = 72), low- and high-grade cervical squamous intraepithelial lesions (SILs) (n =
      55 and 53, respectively) and cervical carcinomas (n = 47) were screened for human
      papillomavirus (HPV) types 6, 11, 16 and 18 infection by the polymerase chain
      reaction. The prevalence of multiple HPV infections in patients with normal
      cervices, low-grade SILs, high-grade SILs and cervical carcinomas was 22.2%,
      61.8%, 41.5% and 21.3%, respectively, while the prevalence of a single-type
      infection was 36.1%, 21.8%, 30.2% and 61.7%, respectively. HPV 16/11 and 16/18
      were the most common combinations observed in multiple infections. Multiple HPV
      infections were seen most frequently in patients with low-grade SILs, and the
      prevalence decreased with increasing severity of cervical neoplasia. In contrast,
      infection with a single HPV type was most commonly observed in patients with
      cervical carcinoma, and the prevalence decreased with decreasing severity of
      cervical neoplasia. HPV 16 was the predominant single-type infection in patients
      with cervical carcinoma and this prevalence decreased steadily with decreasing
      severity of cervical neoplasia. Conversely, HPV 11 was the predominant single
      type infection in patients with normal cervices. This prevalence decreased with
      increasing severity of cervical neoplasia. Patients with low-grade SILs had a
      higher prevalence of HPVs, regardless of single or multiple infection status, and
      larger copy numbers of virus genome were seen more frequently in patients with
      more severe lesions.

PMID- 9003748
TI  - Surface properties of diarrhoeagenic Escherichia coli isolates.
AB  - The surface properties of various Escherichia coli isolates associated with
      diarrhoeal illness were compared by aqueous partitioning between polyethylene
      glycol (PEG) and Dextran phases. Two well characterised strains of
      enteropathogenic E. coli (EPEC) were found to be very hydrophobic, based on the
      critical polymer concentration. EPEC strain E2348 cured of the EPEC adherence
      factor (EAF) plasmid had much reduced surface hydrophobicity. Partitioning of a
      series of diarrhoeagenic E. coli strains demonstrated that the majority of EAF+
      EPEC strains were significantly more hydrophobic than EAF- EPEC strains. E. coli
      strains defined as enteroaggregative on the basis of hybridisation with a
      specific DNA probe showed much greater heterogeneity in their partitioning
      behaviour, possibly indicating that the AAF/I pili were not expressed in all
      strains. The E. coli K-12 strain used as a transformation host for adhesion
      studies had very low surface hydrophobicity but had a detectable negative charge.
      No alteration in these properties was observed when transformed with EPEC and
      recombinant plasmids known to specify adherence to tissue culture cells.

PMID- 9003747
TI  - Induction of IL-2 and IFN-gamma in BALB/c mice immunised with subunit influenza A
      vaccine in combination with whole cell or acellular DTP vaccine.
AB  - Splenocytes from mice immunised with two doses of subunit influenza
      A/Beijing/353/89 vaccine mixed with whole cell DTP (wDTP), acellular DTP (aDTP)
      or PBS were collected 7 and 10 days after the second immunisation, and re
      stimulated with subunit influenza vaccine or live virus in vitro. Interleukin-2
      (IL-2) and interferon-gamma (IFN-gamma) were assayed in supernates from these
      cultures by an ELISA procedure. Splenocytes from mice given subunit influenza
      vaccine in wDTP produced greater than two-fold and greater than five-fold
      responses of IL-2 and IFN-gamma, respectively, compared with splenocytes from
      mice immunised with subunit vaccine alone. In contrast, the response of
      splenocytes from mice immunised with subunit vaccine in saline or aDTP was
      similar, significantly less than for vaccine in wDTP (p < 0.01) and only slightly
      greater than for controls (p < 0.05). The production of IL-2 and IFN-gamma by
      these spleen cells was not significantly different on days 7 and 10 post
      immunisation. Previous reports have shown that wDTP and aDTP enhance the serum
      antibody response of mice to influenza vaccine, but wDTP enhanced the response
      100-fold greater than aDTP, and induced greater IgG2a and IgG2b subclass antibody
      responses; this last result indicates a cell-mediated immune response to vaccine.
      The present studies confirm these earlier findings; furthermore, as the IL-2 and
      IFN-gamma responses of splenocytes are associated with Th-1 subset T-lymphocyte
      response, the findings indicate a cytotoxic T-cell response to immunisation. The
      results indicate that influenza vaccine combined with wDTP induced a cell
      mediated response in mice, which could confer a more solid immunity to challenge
      virus infection.

PMID- 9003749
TI  - Role of Staphylococcus aureus surface adhesins in orthopaedic device infections:
      are results model-dependent?
AB  - Bacterial colonisation of prosthetic material can lead to clinical infection or
      implant failure, or both, often requiring removal of the device. Adherence of
      Staphylococcus aureus to bioprosthetic materials is mediated by adhesins
      belonging to the MSCRAMM (microbial surface components recognising adhesive
      matrix molecules) family of microbial cell surface proteins. The objective of
      this study was to compare the virulence of a mutant strain of S. aureus Newman
      that possesses all three fibrinogen-, fibronectin- and collagen-binding MSCRAMMs
      (MSCRAMM-positive strain) with that of a mutant strain that lacks all three types
      of MSCRAMMs (MSCRAMM-negative strain) in a rabbit model of orthopaedic device
      related infection. After a hole was drilled into the knee joint of each animal, a
      group of 10 rabbits was inoculated with the MSCRAMM-positive strain and another
      group of 10 rabbits received the MSCRAMM-negative strain. A stainless steel screw
      was then placed into the drilled hole. Two weeks later, the rabbits were killed
      and serum samples, bone tissue and implants were harvested for bacteriological
      and histopathological evaluation. No significant difference in infection rates
      was demonstrated between the two groups. The ability to delineate the role of S.
      aureus surface adhesins in causing orthopaedic device-related infection could be
      model-dependent.

PMID- 9003751
TI  - Mucosa-associated bacterial flora of the human colon.
AB  - Biopsy samples of mucosa were taken during colonoscopy from the proximal colon
      and rectum of 12 patients, six with ulcerative colitis (UC) and six with non
      inflammatory conditions. After anaerobic transport to the laboratory, biopsy
      specimens were examined by quantitative bacteriological culture on selective and
      non-selective media for total aerobic count, total anaerobic count, Bacteroides
      spp., lactobacilli, bifidobacteria and asaccharolytic, lactic acid producers.
      Isolates of the genus Bacteroides were identified to species level. Counts from
      proximal colonic and rectal biopsy samples in the same patient were not
      significantly different. Viable aerobic counts (aerobes and facultative
      organisms) ranged from 2.4 x 10(3) to 1.3 x 10(6) cfu/sample biopsy (5.6 mg) and
      total anaerobic counts were 10-10(2) times higher at (1.4 x 10(5))-(3 x 10(7))
      cfu/sample. Bacteroides spp. predominated at both sites (range 8.6 X 10(4) to 1.4
      x 10(7) cfu/sample), comprising 66% of total counts from proximal colon (range in
      individual patients 31-80%) and 68.5% from rectum (range 38-91%). Lactobacilli
      were isolated from eight biopsy samples from five patients, counts ranging from
      3.6 X 10(2) to 1 X 10(5) cfu/sample; bifidobacteria were isolated from both sites
      from 10 of the 12 patients, counts ranging from 50 to 1.8 x 10(6) cfu/sample.
      From the 24 biopsy samples, 235 isolates representing 11 species of Bacteroides
      were identified. For any individual patient, only a few species (2-7; mean 4.4)
      of Bacteroides were found, with just one or two species predominating. B.
      vulgatus was cultured from both samples of seven patients (where it was the major
      isolate in four) and from single samples of two others; B. fragilis was cultured
      from both sites in six patients, being the major isolate in one patient and
      second commonest in three, but was not detected in the other six; the majority of
      other isolates were B. merdae/distasonis, B. ovatus, B. thetaiotaomicron and B.
      uniformis. B. thetaiotaomicron was isolated from both biopsy samples in all three
      UC patients with active inflammation (16 of the 60 isolates from these patients)
      but from only four of the other 18 samples from non-inflamed colonic mucosa (nine
      of 175 isolates).

PMID- 9003750
TI  - Effect of lactulose on short-chain fatty acids and lactate production and on the
      growth of faecal flora, with special reference to Clostridium difficile.
AB  - Lactulose exerts a beneficial effect on hepatic encephalopathy by decreasing
      toxic short-chain (iC4-nC6) fatty acid (isobutyrate, butyrate, isovalerate,
      valerate, isocaproate and caproate) production. However, the precise mechanism by
      which lactulose exerts this effect remains uncertain. This study investigated the
      effect of lactulose on faecal flora, particularly Clostridium difficile, which
      produces mostly iC4-nC6 fatty acids. An in-vitro faecal incubation system was
      used to estimate how lactulose influences production of short-chain (C2-nC6)
      fatty acids and lactate. Faecal specimens were collected from patients with liver
      cirrhosis, who carried C. difficile in the colon. Supplementation of lactulose
      along with blood in faecal specimens decreased iC4-nC6 fatty acids production and
      increased acetate and lactate production, resulting in increased faecal acidity.
      These changes were statistically significant when compared with supplementation
      by blood alone. Quantitative faecal culture demonstrated that lactulose
      supplementation suppressed the growth of C. difficile and Bacteroides spp. (B.
      fragilis group), iC4-nC6 fatty acids-producing organisms. These results suggest
      that decreased faecal levels of iC4-nC6 fatty acids after lactulose
      supplementation may be related to suppression of iC4-nC6 fatty acids-producing
      faecal organisms, especially C. difficile.

PMID- 9003752
TI  - The effect of sample storage on polymerase chain reaction-based detection of
      Toxoplasma gondii in amniotic fluids.
AB  - The effects of sample storage, target preparation and annealing temperature on a
      nested polymerase chain reaction (PCR) test for Toxoplasma gondii DNA were
      investigated with experimentally seeded amniotic fluids to simulate congenital
      infection. Aliquots of 17 amniotic fluid samples remaining after investigation
      for conditions other than toxoplasmosis and seeded to contain small numbers of T.
      gondii tachyzoites, were tested after storage for up to 2 weeks. There was no
      deterioration in test sensitivity on samples stored for 1-2 weeks at room
      temperature; thus, samples sent by post to reference laboratories are acceptable
      for examination. There was no significant difference in the results from two
      target preparation methods or two different annealing temperatures. One-to-ten
      parasites were detectable in 13 of 17 test samples. The significant feature in
      the remaining four samples was the use of washed stored parasites to seed the
      amniotic fluids rather than any feature of the amniotic fluids used or the test.
      False positive results were found in up to 15% of unseeded amniotic fluid
      samples, which contrasts with only 1.9% for the same PCR test in other routine or
      negative control samples tested as part of the laboratory's reference diagnostic
      work. The difference illustrates the increased risk of cross-contamination in PCR
      when the majority of specimens tested are positive. The results suggest that PCR
      techniques are likely to be sensitive and effective tools for the routine
      diagnosis of congenital toxoplasma infection.

PMID- 9003753
TI  - Floral symmetry.

PMID- 9003754
TI  - Crystal structure of a coagulogen, the clotting protein from horseshoe crab: a
      structural homologue of nerve growth factor.
AB  - The clotting cascade system of the horseshoe crab (Limulus) is involved in both
      haemostasis and host defence. The cascade results in the conversion of
      coagulogen, a soluble protein, into an insoluble coagulin gel. The clotting
      enzyme excises the fragment peptide C from coagulogen, giving rise to aggregation
      of the monomers. The crystal structure of coagulogen reveals an elongated
      molecule that embraces the helical peptide C fragment. Cleavage and removal of
      the peptide C would expose an extended hydrophobic cove, which could interact
      with the hydrophobic edge of a second molecule, leading to a polymeric fibre. The
      C-terminal half of the coagulogen molecule exhibits a striking topological
      similarity to the neurotrophin nerve growth factor (NGF), providing the first
      evidence for a neurotrophin fold in invertebrates. Similarities between
      coagulogen and Spatzle, the Drosophila ligand of the receptor Toll, suggest that
      the neurotrophin fold might be considered more ancient and widespread than
      previously realized.

PMID- 9003755
TI  - Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A
      resolution.
AB  - Protein phosphatase 2C (PP2C) is a Mn2+- or Mg2+-dependent protein Ser/Thr
      phosphatase that is essential for regulating cellular stress responses in
      eukaryotes. The crystal structure of human PP2C reveals a novel protein fold with
      a catalytic domain composed of a central beta-sandwich that binds two manganese
      ions, which is surrounded by alpha-helices. Mn2+-bound water molecules at the
      binuclear metal centre coordinate the phosphate group of the substrate and
      provide a nucleophile and general acid in the dephosphorylation reaction. Our
      model presents a framework for understanding not only the classical Mn2+/Mg2+
      dependent protein phosphatases but also the sequence-related domains of
      mitochondrial pyruvate dehydrogenase phosphatase, the Bacillus subtilus
      phosphatase SpoIIE and a 300-residue domain within yeast adenyl cyclase. The
      protein architecture and deduced catalytic mechanism are strikingly similar to
      the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C
      shares no sequence similarity, suggestive of convergent evolution of protein
      Ser/Thr phosphatases.

PMID- 9003757
TI  - The 2.8 A crystal structure of Gla-domainless activated protein C.
AB  - The structure of the Gla-domainless form of the human anticoagulant enzyme
      activated protein C has been solved at 2.8 A resolution. The light chain is
      composed of two domains: an epidermal growth factor (EGF)-like domain modified by
      a large insert containing an additional disulfide, followed by a typical EGF-like
      domain. The arrangement of the long axis of these domains describes an angle of
      approximately 80 degrees. Disulfide linked to the light chain is the catalytic
      domain, which is generally trypsin-like but contains a large insertion loop at
      the edge of the active site, a third helical segment, a prominent cationic patch
      analogous to the anion binding exosite I of thrombin and a trypsin-like Ca[II]
      binding site. The arrangement of loops around the active site partially restricts
      access to the cleft. The S2 and S4 subsites are much more polar than in factor Xa
      and thrombin, and the S2 site is unrestricted. While quite open and exposed, the
      active site contains a prominent groove, the surface of which is very polar with
      evidence for binding sites on the primed side, in addition to those typical of
      the trypsin class found on the non-primed side.

PMID- 9003758
TI  - The crystal structure of staphylococcal enterotoxin type D reveals Zn2+-mediated
      homodimerization.
AB  - Bacterial superantigens, including the staphylococcal enterotoxins, are the most
      potent activators of T cells known and have been suggested as a causative factor
      in Gram-positive shock in humans. Staphylococcal enterotoxin D (SED) is dependent
      upon Zn2+ for high affinity interactions with MHC class II molecules and thus SED
      was co-crystallized with Zn2+. The crystal structure of SED has been determined
      in two different space groups, at 2.3 and 3.0 A resolution respectively. The
      three-dimensional structure of SED is similar to structures of other bacterial
      superantigens, although this study has revealed that SED has the unique
      capability of forming dimers in the presence of Zn2+. The high affinity Zn2+ site
      used in dimer formation is located on the surface of the beta-sheet in the C
      terminal domain. Two bound metal ions are coordinated by residues from both
      molecules in the dimer interface and thus contribute directly to formation of the
      dimer. A second Zn2+ site is located on the surface close to the domain interface
      of the molecule. The unique feature of SED in forming a Zn2+-dependent homodimer
      seems to facilitate novel and biologically relevant multimeric interactions with
      MHC class II molecules, as shown by the induction of cytokine mRNA in human
      monocytes when exposed to SED and SED mutants.

PMID- 9003756
TI  - Giant protein kinases: domain interactions and structural basis of
      autoregulation.
AB  - The myosin-associated giant protein kinases twitchin and titin are composed
      predominantly of fibronectin- and immunoglobulin-like modules. We report the
      crystal structures of two autoinhibited twitchin kinase fragments, one from
      Aplysia and a larger fragment from Caenorhabditis elegans containing an
      additional C-terminal immunoglobulin-like domain. The structure of the longer
      fragment shows that the immunoglobulin domain contacts the protein kinase domain
      on the opposite side from the catalytic cleft, laterally exposing potential
      myosin binding residues. Together, the structures reveal the cooperative
      interactions between the autoregulatory region and the residues from the
      catalytic domain involved in protein substrate binding, ATP binding, catalysis
      and the activation loop, and explain the differences between the observed
      autoinhibitory mechanism and the one found in the structure of calmodulin
      dependent kinase I.

PMID- 9003760
TI  - Mutagenesis of a stacking contact in the MS2 coat protein-RNA complex.
AB  - The thermodynamic contribution of a stacking interaction between Tyr85 in MS2
      coat protein and a single-stranded pyrimidine in its RNA binding site has been
      examined. Mutation of Tyr85 to Phe, His, Cys, Ser and Ala decreased the RNA
      affinity by 1-3 kcal/mol under standard binding conditions. Since the Phe, His
      and Cys 85 proteins formed UV photocrosslinks with iodouracil-containing RNA at
      the same rate as the wild-type protein, the mutant proteins interact with RNA in
      a similar manner. The pH dependence of KD for the Phe and His proteins differs
      substantially from the wild-type protein, suggesting that the titration of
      position 85 contributes substantially to the binding properties. Experiments with
      specifically substituted phosphorothioate RNAs confirm a hydrogen bond between
      the hydroxyl group of tyrosine and a phosphate predicted by the crystal
      structure.

PMID- 9003759
TI  - Adenovirus 3 penton dodecahedron exhibits structural changes of the base on fibre
      binding.
AB  - It was recently shown that co-expression of adenovirus type 3 (Ad3) penton base
      and fibre in the baculovirus system produces dodecahedral particles, as does the
      expression of the penton base alone. The structure of both of these dodecahedral
      particles, with and without fibre, has been determined by cryoelectron microscopy
      and 3-dimensional reconstruction techniques to a resolution of 25 and 20 A,
      respectively. The general form of the penton base resembles that of the base
      protein in the recent reconstruction of adenovirus type 2. There is a remarkable
      difference in the penton base structure with and without the fibre. The five
      small protuberances on the outer surface of each base move away from the 5-fold
      axis by approximately 15 A when the fibre is present. These protuberances are of
      relatively low density and most probably represent a flexible loop possibly
      containing the RGD site involved in integrin binding. The fibre is apparently
      bound to the outer surface of the penton base, rather than inserted into it. The
      fibre is flexible and the shaft contains two distinct globular regions 26 A in
      diameter. The volume of the inner cavity of the dodecahedron is 350 +/- 100 nm3.
      This small volume precludes the use of the inner cavity to house genetic
      information for gene therapy; however, the possibility remains of linking the
      gene to the dodecahedron surface in the hope that it will be internalized with
      the dodecahedron.

PMID- 9003761
TI  - Cloning, functional expression and brain localization of a novel unconventional
      outward rectifier K+ channel.
AB  - Human TWIK-1, which has been cloned recently, is a new structural type of weak
      inward rectifier K+ channel. Here we report the structural and functional
      properties of TREK-1, a mammalian TWIK-1-related K+ channel. Despite a low amino
      acid identity between TWIK-1 and TREK-1 (approximately 28%), both channel
      proteins share the same overall structural arrangement consisting of two pore
      forming domains and four transmembrane segments (TMS). This structural similarity
      does not give rise to a functional analogy. K+ currents generated by TWIK-1 are
      inwardly rectifying while K+ currents generated by TREK-1 are outwardly
      rectifying. These channels have a conductance of 14 pS. TREK-1 currents are
      insensitive to pharmacological agents that block TWIK-1 activity such as quinine
      and quinidine. Extensive inhibitions of TREK-1 activity are observed after
      activation of protein kinases A and C. TREK-1 currents are sensitive to
      extracellular K+ and Na+. TREK-1 mRNA is expressed in most tissues and is
      particularly abundant in the lung and in the brain. Its localization in this
      latter tissue has been studied by in situ hybridization. TREK-1 expression is
      high in the olfactory bulb, hippocampus and cerebellum. These results provide the
      first evidence for the existence of a K+ channel family with four TMS and two
      pore domains in the nervous system of mammals. They also show that different
      members in this structural family can have totally different functional
      properties.

PMID- 9003762
TI  - Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme.
AB  - It took at least a decade to realize that the toxic gas NO is the physiological
      activator of soluble guanylyl cyclase (sGC), thereby acting as a signaling
      molecule in the nervous and cardiovascular systems. Despite its rather poor sGC
      activating property, CO has also been implicated as a physiological stimulator of
      sGC in neurotransmission and vasorelaxation. Here, we establish YC-1 as a novel
      NO-independent sGC activator that potentiates both CO- and NO-induced sGC
      stimulation. As this potentiating effect is also observed with protoporphyrin IX
      which activates sGC independently of a gaseous ligand, we conclude that
      stabilization of the enzyme's active configuration is the underlying mechanism of
      YC-1's action. Moreover, the results obtained with YC-1 reveal that CO is capable
      of stimulating sGC to a degree similar to NO, and thus provide the molecular
      basis for CO functioning as a signaling molecule.

PMID- 9003763
TI  - Primitive lymphohematopoietic precursor cell lines generated in culture from day
      7 early-mid-primitive streak stage mouse embryo.
AB  - During mouse development, the first lymphohematopoietic precursor cells and
      myeloid or erythroid cell lineage-determined cells can be detected in the yolk
      sac at days 8-8.5 of gestation. The characteristics of the cells that give rise
      to these yolk sac primitive lymphohematopoietic cells and the molecular events
      controlling this process remain poorly defined. We show here that cell
      suspensions from day 7 early-mid-primitive streak stage embryo proper generated
      early immature PgP-1+ Joro 177+ Lin- hematopoietic cells and some Mac-1+ myeloid
      and TER 119+ erythroid cells after co-culture with the yolk sac-derived stromal
      cell line YS6 without addition of exogenous cytokines. Purified Lin-
      hematopoietic cells generated in these cultures did not express genes known to be
      transcribed at early stages of lymphoid, myeloid or erythroid cell
      differentiation and were able to give rise to T and B lymphocytes, myeloid cells
      and erythroid cells after appropriate further induction in vitro. Several cell
      lines were established in culture with a mixture of four cytokines from the PgP
      1+ Joro 177+ Lin- cell population. The cell lines shared phenotypic and genotypic
      characteristics with the PgP-1+ Joro 177+ Lin- cell population generated in
      culture from day 7 embryo proper and they were able to reconstitute the
      lymphohematopoietic system of irradiated mice. Taken together these results
      support a model of lymphohematopoiesis in which cells from day 7 early-mid
      primitive streak mouse embryo proper migrate and colonize the visceral yolk sac.
      There they generate primitive lymphohematopoietic precursor cells and the first
      erythroid and myeloid hematopoietic cells under the influence of yolk sac stromal
      cells like the YS6 cells described here.

PMID- 9003764
TI  - Effect of constant light and circadian entrainment of perS flies: evidence for
      light-mediated delay of the negative feedback loop in Drosophila.
AB  - Light is the dominant environmental cue that provides temporal information to
      circadian pacemakers. In Drosophila melanogaster some period gene mutants have
      altered free-running circadian periods but entrain to 24 h light-dark cycles. To
      address the mechanism of light entrainment in Drosophila, we examined the effects
      of constant light on the period gene (per) and timeless gene (tim) products in
      wild-type and perS flies. The results indicate that light affects three features
      of the PER-TIM program: PER and TIM phosphorylation, PER and TIM accumulation,
      and per and tim RNA cycling. A post-transcriptional effect on the PER-TIM complex
      is the likely primary clock target, which then delays the subsequent decrease in
      per and tim RNA levels. This is consistent with a negative feedback loop, in
      which the PER-TIM complex contributes to the decrease in per and tim RNA levels,
      presumably at the transcriptional level. There are enhanced constant light
      effects on the perS mutant, which further support negative feedback as well as
      support its importance to entrainment of these flies to a 24 h cycle, far from
      their intrinsic period of 19 h. The perS mutant leads to a truncated protein
      accumulation phase and a subsequent premature perS RNA increase. A standard 24 h
      light-dark cycle delays the negative feedback circuit and extends the RNA and
      protein profiles, compensating for the accelerated RNA increase and restoring the
      rhythms to wild-type-like periodicity.

PMID- 9003765
TI  - Analysis of mammalian 20S proteasome biogenesis: the maturation of beta-subunits
      is an ordered two-step mechanism involving autocatalysis.
AB  - Maturation of eukaryotic 20S proteasomes involves the processing of beta-subunits
      by limited proteolysis. To study the processing mechanism we analysed different
      point mutations of the beta-subunit LMP2 in transfected human T2 cells. Here we
      show that the presence of the intact Gly-1Thr1 consensus motif and Lys33 are
      essential for correct processing. Mutation of Thr1, the active site residue in
      mature subunits, or of Lys33, results in complete inhibition of processing at the
      consensus site. In addition, proprotein processing in vitro of wild-type LMP2,
      incorporated in immature 16S precursor complexes, can be blocked by a proteasome
      specific inhibitor. While the processing of inhibitor-treated wild-type
      proprotein was completely prevented, the site-directed mutagenesis of LMP2
      results in processing intermediates carrying an extension of 8-10 residues
      preceding Thr1, suggesting an additional cleavage event within the prosequence.
      Furthermore, exchange of mammalian prosequences interferes with processing
      efficiency and suggests subunit specificity. Based on our data we propose a model
      for self-activation of proteasomal beta-subunits in which residue Thr1 serves as
      nucleophile and Lys33 as proton donor/acceptor. We provide evidence that subunit
      processing of mammalian beta-subunits proceeds via a novel ordered two-step
      mechanism involving autocatalysis.

PMID- 9003767
TI  - Distinct antigen MHC class II complexes generated by separate processing
      pathways.
AB  - The peptide binding site of MHC class II molecules is open at both ends and,
      therefore, does not restrict the length of the bound ligand. Here we show that a
      partially folded protein antigen (*HEL) spontaneously formed SDS-unstable
      complexes with the purified MHC class II molecule I-Ak (Ak). These complexes were
      also detected on the surface of antigen-presenting cells (APCs) where they
      stimulated T cells. However, they rapidly disappeared after endocytosis.
      Intracellular processing of *HEL gave rise to SDS-stable, long-lived Ak complexes
      containing *HEL peptides and, unexpectedly, full-length *HEL. Both SDS-stable
      products were formed in low pH compartments and then transported to the plasma
      membrane. In contrast to *HEL peptides, the stable association of *HEL occurred
      in an alternative pathway that required mature class II molecules and did not
      involve HLA-DM or proteases. SDS-stable *HEL-Ak complexes were formed by a
      reaction of endosomal Ak with endocytosed *HEL, but not by direct conversion of
      SDS-unstable complexes derived from the plasma membrane. Our work establishes a
      fundamental difference between the two MHC class II loading pathways and for the
      first time demonstrates a full-length protein as a product of antigen processing.

PMID- 9003766
TI  - Identification and characterization of HsIV HsIU (ClpQ ClpY) proteins involved in
      overall proteolysis of misfolded proteins in Escherichia coli.
AB  - Heat shock response in Escherichia coli is autoregulated. Consistent with this,
      mutations in certain heat shock genes, such as dnaK, dnaJ, grpE or htrC lead to a
      higher constitutive heat shock gene expression at low temperatures. A similar
      situation occurs upon accumulation of newly synthesized peptides released
      prematurely from the ribosomes by puromycin. We looked for gene(s) which, when
      present in multicopy, prevent the constitutive heat shock response associated
      with htrC mutant bacteria or caused by the presence of puromycin. One such locus
      was identified and shown to carry the recently sequenced hslV hslU (clpQ clpY)
      operon. HslV/ClpQ shares a very high degree of homology with members of the beta
      type subunit, constituting the catalytic core of the 20S proteasome. HslU/ClpY is
      50% identical to the ClpX protein of E. coli, which is known to present large
      polypeptides to its partner, the ATP-independent proteolytic enzyme ClpP. We show
      that, in vivo, HslV and HslU interact and participate in the degradation of
      abnormal puromycylpolypeptides. Biochemical evidence suggests that HslV/ClpQ is
      an efficient peptidase whose activity is enhanced by HslU/CIpY in the presence of
      ATP.

PMID- 9003768
TI  - N-linked oligosaccharides are necessary and sufficient for association of
      glycosylated forms of bovine RNase with calnexin and calreticulin.
AB  - Calnexin and calreticulin are lectin-like molecular chaperones that promote
      folding and assembly of newly synthesized glycoproteins in the endoplasmic
      reticulum. While it is well established that they interact with substrate
      monoglucosylated N-linked oligosaccharides, it has been proposed that they also
      interact with polypeptide moieties. To test this notion, glycosylated forms of
      bovine pancreatic ribonuclease (RNase) were translated in the presence of
      microsomes and their folding and association with calnexin and calreticulin were
      monitored. When expressed with two N-linked glycans in the presence of micromolar
      concentrations of deoxynojirimycin, this small soluble protein was found to bind
      firmly to both calnexin and calreticulin. The oligosaccharides were necessary for
      association, but it made no difference whether the RNase was folded or not. This
      indicated that unlike other chaperones, calnexin and calreticulin do not select
      their substrates on the basis of folding status. Moreover, enzymatic removal of
      the oligosaccharide chains using peptide N-glycosidase F or removal of the
      glucoses by ER glucosidase II resulted in dissociation of the complexes. This
      indicated that the lectin-like interaction, and not a protein-protein
      interaction, played the central role in stabilizing RNase-calnexin/calreticulin
      complexes.

PMID- 9003770
TI  - Autocatalytic polysialylation of polysialyltransferase-1.
AB  - Polysialic acid (PSA) is a specific and highly regulated post-translational
      modification of the neural cell adhesion molecule NCAM. Synthesis of PSA depends
      on the activity of a single enzyme, the polysialyltransferase-1 (PST-1), recently
      cloned from three mammalian species. The present study was carried out to
      investigate the catalytic mechanism of PST-1. Using a newly developed in vitro
      assay system, we demonstrate autopolysialylation for PST-1. The synthesis of PSA
      chains, which involved N-glycosylation sites, occurred immediately after contact
      with the activated sugar donor CMP-Neu5Ac. In contrast to the polysialylation of
      NCAM, where terminal sialylation in either the alpha2,3 or alpha2,6 position is
      required, the autopolysialylation could be started in the asialo-PST-1 isolated
      from CHO cells of the Lec2 complementation group. Pre-formed PSA chains were not
      transferred to NCAM. Nevertheless, the autocatalytic step is likely to be a
      prerequisite for enzymatic activity, since agalacto-PST-1 isolated from Lec8
      cells was functionally inactive. Our data describe a novel route of autocatalytic
      maturation of a glycosyltransferase and thereby provide a new basis for studies
      aimed at elucidating and influencing the catalytic functions of PST-1.

PMID- 9003771
TI  - Mutational analysis of VAMP domains implicated in Ca2+-induced insulin
      exocytosis.
AB  - Vesicle-associated membrane protein-2 (VAMP-2) and cellubrevin are associated
      with the membrane of insulin-containing secretory granules and of gamma
      aminobutyric acid (GABA)-containing synaptic-like vesicles of pancreatic beta
      cells. We found that a point mutation in VAMP-2 preventing targeting to synaptic
      vesicles also impairs the localization on insulin-containing secretory granules,
      suggesting a similar requirement for vesicular targeting. Tetanus toxin (TeTx)
      treatment of permeabilized HIT-T15 cells leads to the proteolytic cleavage of
      VAMP-2 and cellubrevin and causes the inhibition of Ca2+-triggered insulin
      exocytosis. Transient transfection of HIT-T15 cells with VAMP-1, VAMP-2 or
      cellubrevin made resistant to the proteolytic action of TeTx by amino acid
      replacements in the cleavage site restored Ca2+-stimulated secretion. Wild-type
      VAMP-2, wild-type cellubrevin or a mutant of VAMP-2 resistant to TeTx but not
      targeted to secretory granules were unable to rescue Ca2+-evoked insulin release.
      The transmembrane domain and the N-terminal region of VAMP-2 were not essential
      for the recovery of stimulated exocytosis, but deletions preventing the binding
      to SNAP-25 and/or to syntaxin I rendered the protein inactive in the
      reconstitution assay. Mutations of putative phosphorylation sites or of
      negatively charged amino acids in the SNARE motif recognized by clostridial
      toxins had no effect on the ability of VAMP-2 to mediate Ca2+-triggered
      secretion. We conclude that: (i) both VAMP-2 and cellubrevin can participate in
      the exocytosis of insulin; (ii) the interaction of VAMP-2 with syntaxin and SNAP
      25 is required for docking and/or fusion of secretory granules with the plasma
      membrane; and (iii) the phosphorylation of VAMP-2 is not essential for Ca2+
      stimulated insulin exocytosis.

PMID- 9003769
TI  - A microsomal ATP-binding protein involved in efficient protein transport into the
      mammalian endoplasmic reticulum.
AB  - Protein transport into the mammalian endoplasmic reticulum depends on nucleoside
      triphosphates. Photoaffinity labelling of microsomes with azido-ATP prevents
      protein transport at the level of association of precursor proteins with the
      components of the transport machinery, Sec61alpha and TRAM proteins. The same
      phenotype of inactivation was observed after depleting a microsomal detergent
      extract of ATP-binding proteins by passage through ATP-agarose and subsequent
      reconstitution of the pass-through into proteoliposomes. Transport was restored
      by co-reconstitution of the ATP eluate. This eluate showed eight distinct bands
      in SDS gels. We identified five lumenal proteins (Grp170, Grp94, BiP/Grp78,
      calreticulin and protein disulfide isomerase), one membrane protein (ribophorin
      I) and two ribosomal proteins (L4 and L5). In addition to BiP (Grp78), Grp170 was
      most efficiently retained on ATP-agarose. Purified BiP did not stimulate
      transport activity. Sequence analysis revealed a striking similarity of Grp170
      and the yeast microsomal protein Lhs1p which was recently shown to be involved in
      protein transport into yeast microsomes. We suggest that Grp170 mediates
      efficient insertion of polypeptides into the microsomal membrane at the expense
      of nucleoside triphosphates.

PMID- 9003772
TI  - Mycobacterium-containing phagosomes are accessible to early endosomes and reflect
      a transitional state in normal phagosome biogenesis.
AB  - The success of Mycobacterium as a pathogen hinges on its ability to modulate its
      intracellular environment. Mycobacterium avium reside in vacuoles with limited
      proteolytic activity, maintain cathepsin D in an immature form and remain
      accessible to internalized transferrin. Artificial acidification of isolated
      phagosomes facilitated processing of cathepsin D, demonstrating that pH alone
      limits proteolysis in these vacuoles. Moreover, analysis of IgG-bead phagosomes
      at early time points during their formation indicates that these phagosomes also
      acquire LAMP 1 and cathepsin D prior to the accumulation of proton-ATPases, and
      are transiently accessible to sorting endosomes. This suggests that the anomolous
      distribution of endosomal proteins in M. avium-containing vacuoles results from
      their arrested differentiation in an early transitional stage through which all
      phagosomes pass.

PMID- 9003773
TI  - Specific cleavage of the retinoblastoma protein by an ICE-like protease in
      apoptosis.
AB  - Interleukin 1beta-converting enzyme-like (ICE-like) proteases are important
      mediators of apoptosis in diverse cell types and organisms. However, the role of
      these proteases in apoptosis cannot be satisfactorily explained on the basis of
      the physiological functions of their known substrates. Here we show that the C
      terminal 42 amino acid peptide of the retinoblastoma (Rb) protein, an important
      cell cycle regulator with a known anti-apoptotic function, is specifically
      cleaved off by an ICE-like protease in tumour necrosis factor (TNF)- and
      staurosporine-induced apoptosis. Cleavage of Rb induced by TNF was blocked in
      vivo and in vitro by two specific inhibitors of ICE-like proteases, and in vitro
      by a point mutation (Asp886 to Ala) within the ICE-like protease cleavage site of
      Rb, (883)DEAD(886). An antibody raised against the C-terminal 15 amino acid
      peptide of Rb recognized the full-length but not the cleaved form of Rb. The
      extent of Rb cleavage correlated directly with TNF-induced apoptosis in all
      tumour cell lines examined. Cleaved Rb bound cyclin D3 and inhibited the
      transcriptional activity of E2F-1, but failed to bind to the regulatory protein
      MDM2, which has been implicated in apoptosis. As Rb suppresses cell death and its
      C-terminus has important regulatory functions, our results suggest that Rb
      cleavage is an important event in apoptosis.

PMID- 9003774
TI  - The cell death inhibitor Bcl-2 and its homologues influence control of cell cycle
      entry.
AB  - The effect of the cell death inhibitor Bcl-2 and its homologues on cell cycle
      regulation was explored in lymphocytes and cell lines. Expression of a bcl-2
      transgene reduced proliferation of thymocytes and delayed cell cycle entry of
      mitogen-stimulated B and T lymphocytes. Overexpression of Bcl-2, Bcl-xL or
      adenovirus E1B19kD substantially delayed serum stimulation-induced S phase entry
      of quiescent NIH 3T3 fibroblasts. Bcl-2-mediated cell survival and growth
      inhibition are both antagonized by Bax. Bcl-2, Bcl-xL and E1B19kD, but not Bcl-2
      mutants that are defective in blocking apoptosis, suppress growth of colon
      carcinoma cells. This evidence that regulation of cell survival is coupled to
      control of cell growth has implications for normal cell turnover and
      tumorigenesis.

PMID- 9003775
TI  - Bax alpha perturbs T cell development and affects cell cycle entry of T cells.
AB  - Bax alpha can heterodimerize with Bcl-2 and Bcl-X(L), countering their effects,
      as well as promoting apoptosis on overexpression. We show that bax alpha
      transgenic mice have greatly reduced numbers of mature T cells, which results
      from an impaired positive selection in the thymus. This perturbation in positive
      selection is accompanied by an increase in the number of cycling thymocytes.
      Further to this, mature T cells overexpressing Bax alpha have lower levels of
      p27Kip1 and enter S phase more rapidly in response to interleukin-2 stimulation
      than do control T cells, while the converse is true of bcl-2 transgenic T cells.
      These data indicate that apoptotic regulatory proteins can modulate the level of
      cell cycle-controlling proteins and thereby directly impact on the cell cycle.

PMID- 9003776
TI  - Roles of the RAM and ANK domains in signaling by the C. elegans GLP-1 receptor.
AB  - In Caenorhabditis elegans, the GLP-1 receptor acts with a downstream
      transcriptional regulator, LAG-1, to mediate intercellular signaling. GLP-1 and
      LAG-1 are homologs of Drosophila Notch and Su(H) respectively. Here, we
      investigate the functions of two regions of the GLP-1 intracellular domain: the
      ANK repeat domain, which includes six cdc10/ankyrin repeats plus flanking amino
      acids, and the RAM domain, which spans approximately 60 amino acids just inside
      the transmembrane domain. First, we demonstrate that both ANK and RAM domains
      interact with the LAG-1 transcription factor. The interaction between the ANK
      domain and LAG-1 is only observed in nematodes by a co-localization assay and,
      therefore, may be either direct or indirect. By contrast, the interaction between
      the RAM domain and LAG-1 is likely to be direct, since it is observed by co
      precipitation of the proteins in vitro as well as by yeast two-hybrid
      experiments. Second, we demonstrate that the RAM domain, when expressed in
      nematodes without a functional ANK repeat domain, does not mimic the unregulated
      receptor in directing cell fates or interfere with signaling by endogenous
      components. Finally, we show in yeast that the ANK repeats are strong
      transcriptional activators. Furthermore, missense mutations that eliminate
      receptor activity also abolish transcriptional activation by the GLP-1 ANK
      repeats in yeast. We speculate that one possible function for the ANK repeat
      domain is to act as a transcriptional co-activator with LAG-1.

PMID- 9003777
TI  - HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway.
AB  - In mammalian cells, a specific stress-activated protein kinase (SAPK/JNK) pathway
      is activated in response to inflammatory cytokines, injury from heat,
      chemotherapeutic drugs and UV or ionizing radiation. The mechanisms that link
      these stimuli to activation of the SAPK/JNK pathway in different tissues remain
      to be identified. We have developed and applied a PCR-based subtraction strategy
      to identify novel genes that are differentially expressed at specific
      developmental points in hematopoiesis. We show that one such gene, hematopoietic
      progenitor kinase 1 (hpk1), encodes a serine/threonine kinase sharing similarity
      with the kinase domain of Ste20. HPK1 specifically activates the SAPK/JNK pathway
      after transfection into COS1 cells, but does not stimulate the p38/RK or mitogen
      activated ERK signaling pathways. Activation of SAPK requires a functional HPK1
      kinase domain and HPK1 signals via the SH3-containing mixed lineage kinase MLK-3
      and the known SAPK activator SEK1. HPK1 therefore provides an example of a cell
      type-specific input into the SAPK/JNK pathway. The developmental specificity of
      its expression suggests a potential role in hematopoietic lineage decisions and
      growth regulation.

PMID- 9003778
TI  - MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6.
AB  - Mixed lineage kinase-3 (MLK-3) is a 97 kDa serine/threonine kinase with multiple
      interaction domains, including a Cdc42 binding motif, but unknown function. Cdc42
      and the related small GTP binding protein Rac1 can activate the SAPK/JNK and
      p38/RK stress-responsive kinase cascades, suggesting that MLK-3 may have a role
      in upstream regulation of these pathways. In support of this role, we demonstrate
      that MLK-3 can specifically activate the SAPK/JNK and p38/RK pathways, but has no
      effect on the activation of ERKs. Immunoprecipitated MLK-3 catalyzed the
      phosphorylation of SEK1 in vitro, and co-transfected MLK-3 induced
      phosphorylation of SEK1 and MKK3 at sites required for activation, suggesting
      direct regulation of these protein kinases. Furthermore, interactions between MLK
      3 and SEK and MLK-3 and MKK6 were observed in co-precipitation experiments.
      Finally, kinase-dead mutants of MLK-3 blocked activation of the SAPK pathway by a
      newly identified mammalian analog of Ste20, germinal center kinase, but not by
      MEKK, suggesting that MLK-3 functions to activate the SAPK/JNK and p38/RK
      cascades in response to stimuli transduced by Ste20-like kinases.

PMID- 9003779
TI  - The transient receptor potential protein (Trp), a putative store-operated Ca2+
      channel essential for phosphoinositide-mediated photoreception, forms a signaling
      complex with NorpA, InaC and InaD.
AB  - The transient receptor potential protein (Trp) is a putative capacitative Ca2+
      entry channel present in fly photoreceptors, which use the inositol 1,4,5
      trisphosphate (InsP3) signaling pathway for phototransduction. By
      immunoprecipitation studies, we find that Trp is associated into a multiprotein
      complex with the norpA-encoded phospholipase C, an eye-specific protein kinase C
      (InaC) and with the InaD protein (InaD). InaD is a putative substrate of InaC and
      contains two PDZ repeats, putative protein-protein interaction domains. These
      proteins are present in the photoreceptor membrane at about equimolar ratios. The
      Trp homolog analyzed here is isolated together with NorpA, InaC and InaD from
      blowfly (Calliphora) photoreceptors. Compared to Drosophila Trp, the Calliphora
      Trp homolog displays 77% amino acid identity. The highest sequence conservation
      is found in the region that contains the putative transmembrane domains S1-S6
      (91% amino acid identity). As investigated by immunogold labeling with specific
      antibodies directed against Trp and InaD, the Trp signaling complex is located in
      the microvillar membranes of the photoreceptor cells. The spatial distribution of
      the signaling complex argues against a direct conformational coupling of Trp to
      an InsP3 receptor supposed to be present in the membrane of internal
      photoreceptor Ca2+ stores. It is suggested that the organization of signal
      transducing proteins into a multiprotein complex provides the structural basis
      for an efficient and fast activation and regulation of Ca2+ entry through the Trp
      channel.

PMID- 9003780
TI  - Functional analysis of the interaction between the small GTP binding protein
      Cdc42 and the Ste20 protein kinase in yeast.
AB  - STE20 encodes a protein kinase related to mammalian p65Pak which functions in
      several signal transduction pathways in yeast, including those involved in
      pseudohyphal and invasive growth, as well as mating. In addition, Ste20 plays an
      essential role in cells lacking Cla4, a kinase with significant homology to
      Ste20. It is not clear how the activity of Ste20 is regulated in response to
      these different signals in vivo, but it has been demonstrated recently that
      binding of the small GTP binding protein Cdc42 is able to activate Ste20 in
      vitro. Here we show that Ste20 functionally interacts with Cdc42 in a GTP
      dependent manner in vivo: Ste20 mutants that can no longer bind Cdc42 were unable
      to restore growth of ste20 cla4 mutant cells. They were also defective for
      pseudohyphal growth and agar invasion, and displayed reduced mating efficiency
      when mated with themselves. Surprisingly, however, the kinase activity of such
      Ste20 mutants was normal when assayed in vitro. Furthermore, these alleles were
      able to fully activate the MAP kinase pathway triggered by mating pheromones in
      vivo, suggesting that binding of Cdc42 and Ste20 was not required to activate
      Ste20. Wild-type Ste20 protein was visualized as a crescent at emerging buds
      during vegetative growth and at shmoo tips in cells arrested with alpha-factor.
      In contrast, a Ste20 mutant protein unable to bind Cdc42 was found diffusely
      throughout the cytoplasm, suggesting that Cdc42 is required to localize Ste20
      properly in vivo.

PMID- 9003781
TI  - The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that
      for phosphorylation by cyclin A/E-Cdk2.
AB  - Cyclin D-Cdk4/6 and cyclin A/E-Cdk2 are suggested to be involved in
      phosphorylation of the retinoblastoma protein (pRB) during the G1/S transition of
      the cell cycle. However, it is unclear why several Cdks are needed and how they
      are different from one another. We found that the consensus amino acid sequence
      for phosphorylation by cyclin D1-Cdk4 is different from S/T-P-X-K/R, which is the
      consensus sequence for phosphorylation by cyclin A/E-Cdk2 using various synthetic
      peptides as substrates. Cyclin D1-Cdk4 efficiently phosphorylated the G1 peptide,
      RPPTLS780PIPHIPR that contained a part of the sequence of pRB, while cyclins E
      Cdk2 and A-Cdk2 did not. To determine the phosphorylation state of pRB in vitro
      and in vivo, we raised the specific antibody against phospho-Ser780 in pRB. We
      confirmed that cyclin D1-Cdk4, but not cyclin E-Cdk2, phosphorylated Ser780 in
      recombinant pRB. The Ser780 in pRB was phosphorylated in the G1 phase in a cell
      cycle-dependent manner. Furthermore, we found that pRB phosphorylated at Ser780
      cannot bind to E2F-1 in vivo. Our data show that cyclin D1-Cdk4 and cyclin A/E
      Cdk2 phosphorylate different sites of pRB in vivo.

PMID- 9003782
TI  - Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain
      proliferation of B cells but both it and activated CD40 can prolong their
      survival.
AB  - Epstein-Barr virus (EBV) infects human primary B lymphocytes and induces and
      maintains proliferation of these cells efficiently in vitro. Mutants of Epstein
      Barr virus which express EBV nuclear antigen 2 (EBNA2) in a conditional fashion
      allow dissection of individual contributions of viral genes to B cell
      immortalization. EBNA2 is a transcriptional activator of cellular and viral
      genes, including the viral latent membrane protein 1 (LMP1), which is essential
      for B cell immortalization and has oncogenic effects in non-lymphoid cells. To
      analyze the role of this gene in B cell immortalization, LMP1 was constitutively
      expressed in B cells infected with EBV carrying a conditional EBNA2 allele. In
      the absence of functional EBNA2, LMP1 was incapable of sustaining B cell
      proliferation in two independent assays but induced a phenotype consistent with
      prolonged cell viability. Activation of CD40 displayed a comparable phenotype.
      These data indicate that both CD40 activation and LMP1 expression may use a
      common pathway for B cell activation. Proliferation of human B cells, however,
      requires one or more additional signals triggered by EBNA2.

PMID- 9003783
TI  - The transcriptional corepressor DSP1 inhibits activated transcription by
      disrupting TFIIA-TBP complex formation.
AB  - Transcriptional repression of eukaryotic genes is essential for many cellular and
      developmental processes, yet the precise mechanisms of repression remain poorly
      understood. The Dorsal Switch Protein (DSP1) was identified in a genetic screen
      for activities which convert Dorsal into a transcriptional repressor. DSP1 shares
      structural homology with the HMG-1/2 family and inhibits activation by the rel
      transcription factors Dorsal and NF-kappaB in transfection studies. Here we
      investigate the mechanism of transcriptional repression by DSP1. We found that
      DSP1 protein can act as a potent transcriptional repressor for multiple activator
      families in vitro and in transfection studies. DSP1 bound directly to the TATA
      binding protein (TBP), and formed a stable ternary complex with TBP bound to DNA.
      DSP1 preferentially disrupted the DNA binding of TBP complexes containing TFIIA
      and displaced TFIIA from binding to TBP. Consistent with the inhibition of TFIIA
      bound complexes, DSP1 was shown to inhibit activated but not basal transcription
      reactions in vitro. The ability of DSP1 to interact with TBP and to repress
      transcription was mapped to the carboxy-terminal domain which contains two HMG
      boxes. Our results support the model that DSP1 represses activated transcription
      by interfering with the binding of TFIIA, a general transcription factor
      implicated in activated transcription pathways.

PMID- 9003784
TI  - In vivo interactions of the Drosophila Hairy and Runt transcriptional repressors
      with target promoters.
AB  - The Hairy and Runt pair-rule proteins regulate Drosophila segmentation by
      repressing transcription. To explore the ability of these proteins to function as
      promoter-bound regulators in vivo, we examined the effects of Hairy and Runt
      derivatives containing heterologous transcriptional activation domains (HairyAct
      and RunAct). Using this approach, we find that Hairy and Runt efficiently target
      such activation domains to specific segmentation gene promoters, leading to rapid
      induction of transcription. Our results strongly suggest that Hairy normally acts
      as a promoter-bound repressor of fushi tarazu, runt and odd-skipped, and that
      Runt directly represses even-skipped. We also show that expressing HairyAct in
      early blastoderm embryos causes ectopic Sex-lethal expression and male-specific
      lethality, implying that the Hairy-related denominator element Deadpan represses
      Sex-lethal during sex determination by directly recognizing the early Sex-lethal
      promoter.

PMID- 9003785
TI  - The Rel subunit of NF-kappaB-like transcription factors is a positive and
      negative regulator of macrophage gene expression: distinct roles for Rel in
      different macrophage populations.
AB  - The role of Rel in the monocyte/macrophage lineage was examined in mice with an
      inactivated c-rel gene. Although the frequency of monocytic cells was normal in
      Rel-/- mice, we show that Rel serves distinct roles in regulating gene expression
      and immune effector function in different mature macrophage populations.
      Stimulated Rel-/- resident peritoneal macrophages produced higher than normal
      levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte
      colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), but tumour necrosis
      factor-alpha (TNF-alpha) production was not induced. Diminished cytotoxic
      activity exhibited by resident Rel-/- macrophages was consistent with reduced
      nitric oxide production resulting from impaired up-regulation of inducible nitric
      oxide synthase expression. While a similar altered pattern of IL-6 and TNF-alpha
      expression was observed in stimulated Rel-/- peritoneal effusion macrophages,
      cytotoxic activity, nitric oxide, GM-CSF and G-CSF production by these cells was
      normal. The alternate regulation of certain genes in the two macrophage
      populations coincided with different patterns of nuclear Rel/NF-kappaB complexes
      expressed in normal resident and elicited cells. Collectively, these results
      establish that Rel is a positive or negative regulator of transcription in
      macrophages and that Rel has distinct roles in different macrophage populations.

PMID- 9003786
TI  - The lamin B receptor (LBR) provides essential chromatin docking sites at the
      nuclear envelope.
AB  - Morphological studies have established that peripheral heterochromatin is closely
      associated with the nuclear envelope. The tight coupling of the two structures
      has been attributed to nuclear lamins and lamin-associated proteins; however, it
      remains to be determined which of these elements are essential and which play an
      auxiliary role in nuclear envelope-chromatin interactions. To address this
      question, we have used as a model system in vitro reconstituted vesicles
      assembled from octyl glucoside-solubilized nuclear envelopes. Comparing the
      chromosome binding properties of normal, immunodepleted and chemically extracted
      vesicles, we have arrived at the conclusion that the principal chromatin
      anchorage site at the nuclear envelope is the lamin B receptor (LBR), a
      ubiquitous integral protein of the inner nuclear membrane. Consistent with this
      interpretation, purified LBR binds directly to chromatin fragments and decorates
      the surface of chromosomes in a distinctive banding pattern.

PMID- 9003787
TI  - Characterization of the nuclear protein import mechanism using Ran mutants with
      altered nucleotide binding specificities.
AB  - The small nuclear GTP binding protein Ran is required for transport of nuclear
      proteins through the nuclear pore complex (NPC). Although it is known that GTP
      hydrolysis by Ran is essential for this reaction, it has been unclear whether
      additional energy-consuming steps are also required. To uncouple the energy
      requirements for Ran from other nucleoside triphosphatases, we constructed a
      mutant derivative of Ran that has an altered nucleotide specificity from GTP to
      xanthosine 5' triphosphate. Using this Ran mutant, we demonstrate that nucleotide
      hydrolysis by Ran is sufficient to promote efficient nuclear protein import in
      vitro. Under these conditions, protein import could no longer be inhibited with
      non-hydrolysable nucleotide analogues, indicating that no Ran-independent energy
      requiring steps are essential for the protein translocation reaction through the
      NPC. We further provide evidence that nuclear protein import requires Ran in the
      GDP form in the cytoplasm. This suggests that a coordinated exchange reaction
      from Ran-GDP to Ran-GTP at the pore is necessary for translocation into the
      nucleus.

PMID- 9003789
TI  - Polyadenylation accelerates degradation of chloroplast mRNA.
AB  - The expression of chloroplast genes is regulated by several mechanisms, one of
      which is the modulation of RNA stability. To understand how this regulatory step
      is controlled during chloroplast development, we have begun to define the
      mechanism of plastid mRNA degradation. We show here that the degradation petD
      mRNA involves endonucleolytic cleavage at specific sites upstream of the 3' stem
      loop structure. The endonucleolytic petD cleavage products can be polyadenylated
      in vitro, and similar polyadenylated RNA products are detectable in vivo. PCR
      analysis of the psbA and psaA-psaB-rps14 operons revealed other polyadenylated
      endonucleolytic cleavage products, indicating that poly(A) addition appears to be
      an integral modification during chloroplast mRNA degradation. Polyadenylation
      promotes efficient degradation of the cleaved petD RNAs by a 3'-5'
      exoribonuclease. Furthermore, polyadenylation also plays an important role in the
      degradation of the petD mRNA 3' end. Although the 3' end stem-loop is usually
      resistant to nucleases, adenylation renders the secondary structure susceptible
      to the 3'-5' exoribonuclease. Analysis of 3' ends confirms that polyadenylation
      occurs in vivo, and reveals that the extent of adenylation increases during the
      degradation of plastid mRNA in the dark. Based on these results, we propose a
      novel mechanism for polyadenylation in the regulation of plastid mRNA
      degradation.

PMID- 9003788
TI  - Cloning and characterization of SNAP50, a subunit of the snRNA-activating protein
      complex SNAPc.
AB  - The human RNA polymerase II and III snRNA promoters share a common basal element,
      the proximal sequence element (PSE), which is recognized by a complex we refer to
      as the snRNA-activating protein complex (SNAPc). Biochemical purifications
      suggest that SNAPc is composed of at least four polypeptides of 43, 45, 50 and
      190 kDa, as well as variable amounts of the TATA box binding protein, TBP. cDNAs
      encoding the 43 and 45 kDa subunits, SNAP43 and SNAP45, have been isolated, but
      there is no evidence that either of these subunits contacts DNA. Here we report
      the isolation of cDNAs encoding the 50 kDa subunit of SNAPc, SNAP50. The open
      reading frame predicts a 411 amino acid protein, which contains two potential
      zinc finger motifs. Depletions with anti-SNAP50 antibodies inhibit RNA polymerase
      II and III snRNA gene transcription in vitro. SNAP50 interacts with SNAP43 in co
      immunoprecipitation experiments, but not with SNAP45 or TBP. UV cross-linking
      experiments suggest that SNAP50 contacts DNA in the SNAP complex. These results
      are consistent with the same core SNAP complex recognizing the PSEs of RNA
      polymerase II and III snRNA promoters, and provide an initial view of the
      architecture of the SNAP complex.

PMID- 9003790
TI  - General RNA binding proteins render translation cap dependent.
AB  - Translation in rabbit reticulocyte lysate is relatively independent of the
      presence of the mRNA m7G cap structure and the cap binding protein, eIF-4E. In
      addition, initiation occurs frequently at spurious internal sites. Here we show
      that a critical parameter which contributes to cap-dependent translation is the
      amount of general RNA binding proteins in the extract. Addition of several
      general RNA binding proteins, such as hnRNP A1, La autoantigen, pyrimidine tract
      binding protein (hnRNP I/PTB) and the major core protein of cytoplasmic mRNP
      (p50), rendered translation in a rabbit reticulocyte lysate cap dependent. These
      proteins drastically inhibited the translation of an uncapped mRNA, but had no
      effect on translation of a capped mRNA. Based on these and other results, we
      suggest that one function of general mRNA binding proteins in the cytoplasm is to
      promote ribosome binding by a 5' end, cap-mediated mechanism, and prevent
      spurious initiations at aberrant translation start sites.

PMID- 9003792
TI  - Association of the yeast poly(A) tail binding protein with translation initiation
      factor eIF-4G.
AB  - Although the cap structure and the poly(A) tail are on opposite ends of the mRNA
      molecule, previous work has suggested that they interact to enhance translation
      and inhibit mRNA degradation. Here we present biochemical data that show that the
      proteins bound to the mRNA cap (eIF-4F) and poly(A) tail (Pab1p) are physically
      associated in extracts from the yeast Saccharomyces cerevisiae. Specifically, we
      find that Pab1p co-purifies and co-immunoprecipitates with the eIF-4G subunit of
      eIF-4F. The Pab1p binding site on the recombinant yeast eIF-4G protein Tif4632p
      was mapped to a 114-amino-acid region just proximal to its eIF-4E binding site.
      Pab1p only bound to this region when complexed to poly(A). These data support the
      model that the Pablp-poly(A) tail complex on mRNA can interact with the cap
      structure via eIF-4G.

PMID- 9003791
TI  - The catalytic subunit of protein phosphatase 2A associates with the translation
      termination factor eRF1.
AB  - By a number of criteria, we have demonstrated that the translation termination
      factor eRF1 (eukaryotic release factor 1) associates with protein phosphatase 2A
      (PP2A). Trimeric PP2A1 was purified from rabbit skeletal muscle using an affinity
      purification step. In addition to the 36 kDa catalytic subunit (PP2Ac) and
      established regulatory subunits of 65 kDa (PR65) and 55 kDa (PR55), purified
      preparations contained two proteins with apparent Mrs of 54 and 55 kDa. Protein
      microsequencing revealed that the 55 kDa component is a novel protein, whereas
      the 54 kDa protein was identified as eRF1, a protein that functions in
      translational termination as a polypeptide chain release factor. Using the yeast
      two-hybrid system, human eRF1 was shown to interact specifically with PP2Ac, but
      not with the PR65 or PR55 subunits. By deletion analysis, the binding domains
      were found to be located within the 50 N-terminal amino acids of PP2Ac, and
      between amino acid residues 338 and 381 in the C-terminal part of human eRF1.
      This association also occurs in vivo, since PP2A can be co-immunoprecipitated
      with eRF1 from mammalian cells. We observed a significant increase in the amount
      of PP2A associated with the polysomes when eRF1 was transiently expressed in COS1
      cells, and eRF1 immunoprecipitated from those fractions contained associated
      PP2A. Since we did not observe any dramatic effects of PP2A on the polypeptide
      chain release activity of eRF1 (or vice versa), we postulate that eRF1 also
      functions to recruit PP2A into polysomes, thus bringing the phosphatase into
      contact with putative targets among the components of the translational
      apparatus.

PMID- 9003793
TI  - Binding and kinetic properties of HIV-1 reverse transcriptase markedly differ
      during initiation and elongation of reverse transcription.
AB  - We recently showed that primer tRNA3Lys, human immunodeficiency virus type 1 (HIV
      1) RNA and HIV-1 reverse transcriptase (RT) form a specific complex of initiation
      of reverse transcription that can be functionally distinguished from the
      elongation complex, which can be obtained by substituting an 18mer
      oligodeoxyribonucleotide (ODN) for the natural primer (Isel et al., 1996). Here,
      we compared the binding properties and the single and multiple turnover kinetics
      of HIV-1 RT in the initiation and elongation complexes. Even though the
      equilibrium dissociation constants of HIV-1 RT are not very different for the two
      complexes, RT dissociates approximately 200-fold faster from the initiation
      complex. Furthermore, nucleotide incorporation by the pre-formed primer-template
      RT complexes is reduced by a approximately 50-fold factor during initiation of
      reverse transcription, compared with elongation. As a consequence, processivity
      of HIV-1 RT in the initiation complex is close to unity, while it increases by
      four orders of magnitude during elongation, as expected for a replication enzyme.
      This processivity change is reminiscent of the transition from initiation to
      elongation of transcription. Furthermore, our results indicate that the post
      transcriptional modifications of tRNA3Lys play a role similar to that of the
      sigma factor in transcription by the Escherichia coli RNA polymerase: they favour
      the formation of the specific initiation complex but do not affect the
      polymerization rate of the bound enzyme.

PMID- 9003794
TI  - A model for Fis N-terminus and Fis-invertase recognition.
AB  - In this modeling, we show that the elusive Fis N-terminus involved in invertase
      mediated site-specific DNA inversion is, by all indications, a hinged flapping
      loop. The prediction is based on a combined sequence and secondary structure
      alignment against known structures of protein segments, as well as a tetrapeptide
      fragment observed crystallographically. Its validity is strongly supported by the
      ability to interpret consistently the available mutagenesis data pertaining to
      this region including, especially, a series of deletion mutants which until this
      work had been a puzzle in the search for structural explanations. A model for Fis
      invertase recognition is also proposed.

PMID- 9003796
TI  - Anti-cancer drugs and glutathione stimulate vanadate-induced trapping of
      nucleotide in multidrug resistance-associated protein (MRP).
AB  - Multidrug resistance-associated protein (MRP), a member of the ABC superfamily
      transporters, functions as an ATP-dependent efflux pump that extrudes cytotoxic
      drugs from the cells. Although glutathione has been considered to play an
      important role in the function of MRP, there is no convincing evidence that
      glutathione directly interacts with MRP. Here we demonstrate that vanadate
      induced trapping of 8-azido-ATP in MRP was stimulated in the presence of
      glutathione, oxidized glutathione and the anti-cancer drugs VP-16 and
      vincristine. MRP in membrane from a human MRP cDNA transformant was specifically
      photolabeled with 8-azido-[alpha-32P]ATP by the vanadate-trapping technique.
      Vanadate and Mg2+ were required for trapping of nucleotides, and vanadate
      trapping of nucleotides was inhibited by excess ADP as well as ATP. These results
      suggest that a stable inhibitory complex MRP x MgADP x Vi, an analog of the MRP x
      MgADP x Pi transition state complex, is formed in the presence of vanadate.
      Glutathione as well as anti-cancer drugs would directly interact with MRP, and
      stimulate the formation of the transition state of the ATPase reaction of MRP.

PMID- 9003795
TI  - A novel 13 kDa cytoplasmic soluble protein is required for the nucleotide (MgATP)
      modulation of the Na/Ca exchange in squid nerve fibers.
AB  - The Na/Ca exchange is a highly regulated transport mechanism in which MgATP, a
      powerful modulatory intracellular substrate, has important implications for its
      function. As occurs with some preparations, in squid axons, nucleotide regulation
      is lost after membrane vesicle isolation. This has been a significant obstacle in
      the biochemical characterization of the MgATP effect. An important clue in
      solving this long-standing puzzle is presented in this work by showing that
      prolonged intracellular dialysis of squid axons produces a complete run down of
      the MgATP effect. Here we report that a soluble cytoplasmic factor isolated from
      fresh squid axoplasm and brain reconstitutes the MgATP stimulation of the Na
      gradient-dependent 45Ca uptake in squid optic nerve membrane vesicles. Partial
      purification of this factor uncovers the presence of a novel 13 kDa soluble
      cytoplasmic protein (SCPr) which, when microinjected in ATP de-regulated dialyzed
      squid axons, completely restores the MgATP stimulation of Na(o)-dependent Ca
      efflux. We propose that in the squid preparation this SCPr constitutes the link
      between the nucleotide and target effector: the Na/Ca exchanger itself, or other
      plasma membrane structures which may secondarily interact with the exchanger.

PMID- 9003797
TI  - Paramagnetic NMR spectroscopy of native and cobalt substituted manganese
      superoxide dismutase from Escherichia coli.
AB  - Manganese containing superoxide dismutase from E. coli has been investigated
      through paramagnetic NMR spectroscopy. The spectrum of the native form was
      rationalized using a tau(s) = 3x10(-11) s for the Mn(III) ion, consistent with
      previous estimates from NMRD measurements. Mn(III) has been replaced by a Co(II)
      ion and a tentative assignment of the NMR spectrum of the Co(II)-substituted
      derivative has been proposed, based on T1, chemical shifts and 1D-NOE data. The
      metal coordination geometry is provided by three histidines and a carboxylate
      group. The presence of a solvent molecule as a loosely bound fifth ligand is also
      proposed. The NMR data of the Co(II)-substituted derivative of E. coli MnSOD
      differs from those of Co(II)SOD from other bacterial sources. This suggests that
      Co(II) substitution is an efficient method to address the problem of metal ion
      selectivity in superoxide dismutase.

PMID- 9003798
TI  - Siroheme biosynthesis in Saccharomyces cerevisiae requires the products of both
      the MET1 and MET8 genes.
AB  - Siroheme is a uroporphyrinogen III-derivative used by sulfite reductase as a
      prosthetic group. We investigated in Saccharomyces cerevisiae the possible
      involvement in siroheme biosynthesis of three genes, MET1, MET8 and MET20. The
      MET1 gene from S. cerevisiae was cloned and shown to be the same gene as MET20.
      Sequence similitudes as well as complementation studies indicate that Met1p and
      Met8p are both involved in siroheme biosynthesis. In addition, we show formally
      that S. cerevisiae does not need vitamin B12 for growth.

PMID- 9003799
TI  - Selectivity of beta-adrenergic receptor kinase 2 for G protein betagamma
      subunits.
AB  - Phosphorylation of G protein-coupled receptors by beta-adrenergic receptor
      kinases (betaARK) requires the presence of G protein betagamma subunits. We have
      investigated the ability of the two betaARK isoforms to distinguish between
      defined recombinant betagamma subunits. betaARK2 had an about 25% lower specific
      activity than betaARK1 towards rhodopsin and the beta2-adrenergic receptor but
      the two kinases shared the selectivity for betagamma subunits: betagamma
      complexes consisting of beta1 or beta2 in combination with gamma2, gamma5, and
      gamma7 were more efficacious than those with gamma3 or beta1 gamma1. Thus, while
      betaARKs differentiate between defined betagamma subunits, betagamma complexes do
      not discriminate between betaARK isoforms.

PMID- 9003800
TI  - Induction of nuclear factor kappaB and activation protein 1 in postischemic
      myocardium.
AB  - Ischemia/reperfusion induces nuclear factor kappaB (NF-kappaB) and AP-1 in rat
      hearts after 15 min of ischemia followed by reperfusion (R) for various periods
      of time (15 and 30 min, 1, 2, 3, 6, 12, and 24 h). Low levels of NF-kappaB and no
      signal for AP-1 were detected in shams and in non-ischemic tissue distant from
      the ischemic zone. In postischemic tissue, NF-kappaB levels increased
      biphasically with peak levels at 15 min and again at 3 h R. Immunoblotting showed
      minimal NF-kappaB p50 subunit at all times, with changes in p65 similar to EMSA
      results. Northern blots showed low p50 and increased p65 expression levels at
      both 2 and 3 h R. By contrast, AP-1 increased monophasically, with peak levels at
      15 min R, which dropped steadily thereafter. These results indicate that NF
      kappaB and AP-1 are differentially regulated during reperfusion, which may be a
      control mechanism for gene expression in reperfused myocardium.

PMID- 9003801
TI  - The reaction mechanism of phosphomannomutase in plants.
AB  - The enzyme phosphomannomutase catalyzes the interconversion of mannose-1
      phosphate (Man-1-P) and mannose-6-phosphate (Man-6-P). In mammalian cells the
      enzyme has to be activated by transfer of a phosphate group from a sugar-1.6-P2
      (Guha, S.K. and Rose, Z.B. (1985) Arch. Biochem. Biophys. 243, 168). In contrast,
      in the red alga Galdieria sulphuraria the co-substrate (Man-1.6-P2 or Glc-1.6-P2)
      is converted to the corresponding sugar monophosphate while the substrate is
      converted to the sugar bisphosphate in each reaction cycle. Evidence is presented
      that the same reaction mechanism occurs in spinach and yeast.

PMID- 9003802
TI  - Cloning and initial characterization of human and mouse Spot 14 genes.
AB  - The intricate regulation of Spot 14 expression in rat lipogenic tissues has
      provided a useful tool in studying nutritional and hormonal factors involved in
      transcription. To gain insight into its function and its possible involvement in
      human lipid disorders, we cloned human and mouse Spot 14 genes that shared with
      the rat gene a strong homology concerning the deduced amino acid sequence (81 and
      94%, respectively) as well as the promoter region. The mouse promoter was
      characterized by transfection studies, while quantitative RT-PCR and in situ
      hybridization experiments showed that Spot 14 is expressed in human liver and, at
      a high level, in multiple symmetric lipomatosis nodules.

PMID- 9003803
TI  - Aggregation of PDGF-beta receptors in human skin fibroblasts: characterization by
      image correlation spectroscopy (ICS).
AB  - Receptor aggregation is believed to be an important, early step when growth
      factors such as PDGF stimulate proliferation and differentiation of cell
      populations. To investigate receptor aggregation, we utilized a novel biophysical
      technique, image correlation spectroscopy, to study the distribution and
      aggregation state of PDGF-beta receptors on the surface of human dermal
      fibroblasts under various experimental conditions. It was found that the cell
      surface receptors were pre-clustered at 4 degrees C and receptor aggregation
      increased for samples measured at 37 degrees C. Treatment with PDGF-BB had no
      measurable effect on the receptor aggregation state. The results also indicate
      that additions of 10% serum or an inhibitor of tyrosine kinase activity, may
      disperse the receptors. The results of this study are consistent with
      organization of PDGF-beta receptors in pre-existing membrane domains.

PMID- 9003804
TI  - Overlapping and distinct signals through leptin receptor (OB-R) and a closely
      related cytokine signal transducer, gp130.
AB  - The structure of leptin receptor (OB-R) is highly homologous to that of gp130,
      the common signal transducing receptor component for the interleukin-6 family of
      cytokines. Based on this structural similarity, we examined signaling processes
      initiated by OB-R in comparison with those by gp130. Stimulation of either a long
      form of OB-R or gp130 led to tyrosine phosphorylation of STAT3, whereas
      stimulation of the truncated form of OB-R that is predominantly expressed in
      dbldb mice failed to do so. Stimulation of the long form OB-R did not induce
      tyrosine phosphorylation of a Src homology domain 2 containing protein tyrosine
      phosphatase, SHP-2, while stimulation of gp130 did. In contrast, activation of
      p42ERK2 is mediated by either the long form OB-R or gp130. Two closely related
      molecules, OB-R and gp130, thus appear to mediate overlapping but distinct
      signaling procedures.

PMID- 9003805
TI  - Expression of receptors for native and chemically modified low-density
      lipoproteins in brain microvessels.
AB  - Despite the importance of cholesterol metabolism in the central nervous system,
      only relatively few studies have dealt with the cerebral uptake and transport of
      lipids into the brain compartment. These functions are mediated by the
      endothelium of brain microvessels, which forms the anatomical basis of the blood
      brain barrier. By a reverse transcriptase PCR study of messenger RNA expression
      we could show, in bovine brain microvessels, the presence of transcripts of
      native low-density lipoprotein receptor and of both type I and II scavenger
      receptors. Brain microvessels therefore appear to play an active role in the
      uptake of native and modified low-density lipoproteins.

PMID- 9003806
TI  - Overlapping distribution of K(ATP) channel-forming Kir6.2 subunit and the
      sulfonylurea receptor SUR1 in rodent brain.
AB  - ATP-sensitive K+ channels comprise a complex of at least two proteins: a member
      of the inwardly rectifying Kir6 family (e.g. Kir6.2) and a sulphonylurea receptor
      (e.g. SUR1) which belongs to the ATP-binding cassette (ABC) superfamily. Using
      specific radiolabeled antisense oligonucleotides, the cellular localization of
      both mRNAs was investigated in the rodent brain by in situ hybridization. The
      distribution of both transcripts was widespread throughout the brain and showed a
      high degree of overlap with peak expression levels in the hippocampus, neocortex,
      olfactory bulb, cerebellum, and several distinct nuclei of the midbrain and
      brainstem, indicating their important role in vital brain function.

PMID- 9003807
TI  - Binding of the N-terminal 63 kDa portion of connectin/titin to alpha-actinin as
      revealed by the yeast two-hybrid system.
AB  - Connectin/titin is a 3000 kDa protein which links the myosin filament to the Z
      line in vertebrate striated muscle sarcomeres. To search for the Z-line proteins
      to which connectin binds, the yeast two-hybrid system was applied using cDNA
      coding the N-terminal 63 kDa fragment of connectin. Two clones coding the C
      terminal half region of alpha-actinin (amino acids, 343-897 and 446-897) were
      obtained. Enzyme-linked immunosorbent assay clearly demonstrated the interactions
      of alpha-actinin and the N-terminal 63 kDa fragment of connectin in vitro. Thus
      it is concluded that the N-terminal 63 kDa portion of connectin binds to alpha
      actinin in the Z-line of myofibrillar sarcomeres.

PMID- 9003808
TI  - Effect of mevalonate availability on the association of G-protein alpha-subunits
      with the plasma membrane in GH4C1 cells.
AB  - We show that the levels and activity of the alpha-subunits of Gs and Gi proteins
      in plasma membrane of GH4C1 cells are regulated by the availability of mevalonate
      (MVA), and not by changes in cholesterol cell content. Changes in the levels of
      MVA, induced by modulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase, determine the amount of both membrane-bound G alpha-subunits, which
      correlated with the activity of their effector adenylyl cyclase. Lipoprotein
      deficient serum (LPDS) decreases cholesterol content and increases both HMG-CoA
      reductase activity and G alpha-subunits in the membrane. Cholesterol and 25
      hydroxycholesterol (25-HC) each repress HMG-CoA reductase and diminish G alpha
      subunit levels. However, while cholesterol cell content is also decreased by 25
      HC, exogenous cholesterol increases it. In addition, the decrease of both G alpha
      subunits is reversed by the presence of MVA. This regulation appears to be
      mediated by nonsterol products generated from MVA. We assume that the first is
      the prenylation of the gamma-subunits, since the attachment of G alpha-subunits
      to the membrane is dependent on this modification. However, as neither of our
      treatments completely abolished protein prenylation, we conclude that another MVA
      derivative is required in addition to prenyl residues to the presence and
      activity of alpha-subunits in the membrane.

PMID- 9003809
TI  - Expression of a lipocalin in Pichia pastoris: secretion, purification and binding
      activity of a recombinant mouse major urinary protein.
AB  - The proteins of the mouse major urinary protein complex (MUP), members of the
      lipocalin family, bind volatile pheromones and interact with the vomeronasal
      neuroepithelium of the olfactory system. We report the expression of a MUP
      protein using its native signal sequence for secretion in the methylotrophic
      yeast, Pichia pastoris. Mature recombinant MUP (rMUP) is secreted at a
      concentration of 270 mg/l in minimal medium and it is isolated from the culture
      supernatant by one step ion-exchange chromatography in a nearly pure form.
      Binding activity, tested with an odorant molecule which displays high affinity
      for native MUP, indicates that rMUP has a behavior similar to the native one.
      This finding suggests that the protein, and in particular its hydrophobic binding
      pocket, is properly folded.

PMID- 9003810
TI  - The identification of flavonoids as glycosides in human plasma.
AB  - This study describes evidence for the absorption of flavonoids and their presence
      in human plasma in the glycosylated form by HPLC analysis with photodiode array
      detection. Rutin and other quercetin glycosides, phloridzin, as well as an
      anthocyanin are detected simultaneously. In addition, a compound eluting with the
      spectral properties of the aurone family is identified. The results reveal that
      phloretin and quercetin are absorbed from the diet as glycosides. The polyphenols
      are detected in plasma from non-supplemented humans at individual levels in the
      range 0.5-1.6 microM.

PMID- 9003811
TI  - Coexistence of somatostatin receptor subtypes in the human neuroblastoma cell
      line LA-N-2.
AB  - Five distinct human somatostatin receptor subtypes have recently been cloned and
      characterized. Previous studies have suggested that these receptor subtypes might
      display coexistent localization, based on in situ hybridization or immunoblockage
      experiments. Here we provide evidence for coexistence of somatostatin receptor
      subtypes 2 and 5 in the human neuroblastoma cell line LA-N-2, using a combined
      approach with RT-PCR and receptor binding studies with somatostatin analogues.
      Somatostatin receptor subtypes simultaneously localized to a single cell might
      serve distinct functions in terms of targeting to different intraneuronal
      compartments or subtype specificity against so far unidentified somatostatin
      related peptides.

PMID- 9003812
TI  - Functional consequences of disulfide bond formation in gelsolin.
AB  - Gelsolin is an actin monomer binding and filament severing protein synthesized in
      plasma and cytoplasmic forms differing by an N-terminal amino acid extension and
      a disulfide bond between Cys-188 and Cys-201. To determine whether this bond
      altered gelsolin regulation or function, oxidized and reduced plasma gelsolins
      were assayed for severing, monomer binding and nucleation activity at a variety
      of rate-limiting calcium concentrations. The results indicate that the disulfide
      bond in domain 2 of gelsolin influences the transmission of information from C
      terminal regulatory sites to functional sites in the N-terminus.

PMID- 9003813
TI  - Engineering of cholera toxin A-subunit for carriage of epitopes at its amino end.
AB  - The cholera toxin A-subunit (CTA) was genetically engineered at its amino end and
      tested for carriage of epitopes by fusion of the STa heat-stable enterotoxin
      analogue CAELCCNPAC. Efficient holotoxin formation by complementation in trans
      with cholera toxin B-subunit (CTB) indicated no decrease in affinity for CTB but
      evidence of reduced toxicity suggests steric interference by the decapeptide with
      the active site. The holotoxin was stable, able to bind to GM1 and was recognized
      by anti-STa and anti-CTA antibodies. The use of a full-length CTA might have been
      a key step for successful genetic fusions. Based on these findings, it seems
      worthwhile pursue the development of CTA for construction of recombinant mucosal
      immunoadjuvants.

PMID- 9003814
TI  - Respiratory manifestations of tick-borne diseases in the Southeastern United
      States.
AB  - Pulmonary signs and symptoms may provide important differential clues to the
      diagnosis of tick-borne illness incurred in the southern United States.

PMID- 9003815
TI  - Intracranial hemorrhage complicating acute myocardial infarction in the era of
      thrombolytic therapy.
AB  - Cerebrovascular accidents are one of the most serious causes of morbidity in
      patients sustaining an acute myocardial infarction. In patients who do not
      receive thrombolytic therapy, the most common form of stroke is thromboembolic,
      occurring in up to 2.4% of patients, predominantly in those sustaining large
      anterior infarctions. In patients receiving thrombolytic therapy, intracranial
      hemorrhage is the most common form of stroke, occurring in 0.1% to 1.4%.
      Predisposing conditions for intracranial bleeding include low body weight, female
      sex, advanced age, use of oral anticoagulant medication before the administration
      of lytic therapy, diastolic blood pressure greater than 110 mm Hg, and the
      specific thrombolytic agent administered. Hematologic management of the patient
      sustaining a hemorrhagic cerebrovascular accident should include (1)
      discontinuance of thrombolytic therapy, anticoagulants, and antiplatelet agents
      and (2) infusion of cryoprecipitate to replenish fibrinogen. In certain cases,
      administration of fresh frozen plasma, protamine sulfate, and exogenous platelets
      may be required. Finally, evacuation of the hematoma may provide the most
      definitive form of treatment in selected cases.

PMID- 9003816
TI  - Assessing testamentary capacity in elderly people.
AB  - We discuss the assessment of testamentary capacity (ability to execute a valid
      will) in elderly people. Such assessment should include evaluation of the
      person's knowledge regarding the purpose of the will, the extent of the property
      involved, the legal heirs, and how the property is distributed according to the
      will. Some conditions may invalidate a will, including insane delusions and undue
      influence; however, the mere presence of severe mental illness, such as
      schizophrenia or dementia, does not automatically render elderly people
      incompetent to execute a valid will.

PMID- 9003817
TI  - Ceftriaxone versus cefazolin in peripheral arterial operations: a randomized,
      prospective trial.
AB  - Serious morbidity and mortality are associated with postoperative wound
      infections in peripheral vascular surgery. The use of prophylactic antibiotics is
      considered the standard of care, with attention focused on the most efficacious
      agent. A prospective, randomized study was conducted to evaluate the efficacy of
      ceftriaxone versus cefazolin in prevention of postoperative wound infections in a
      group of patients who had peripheral arterial operations between October 1991 and
      February 1993. Patient characteristics associated with an increased risk of
      postoperative wound infection were evaluated. Prophylaxis was provided for 105
      operations with cefazolin and 103 operations with ceftriaxone. The overall wound
      infection rate was 3.85%. Six operations (5.7%) in the cefazolin group were
      complicated by wound infection versus 2 operations (1.9%) in the ceftriaxone
      group. Diabetes (6 infections/64 operations; infection rate, 9%) and a personal
      history of previous aortocoronary bypass (5 infections/49 operations; infection
      rate, 10%) were characteristics associated with an increased chance for
      postoperative wound infection. Ceftriaxone is therapeutically equivalent to
      cefazolin in the prevention of postoperative wound infections in peripheral
      vascular surgery.

PMID- 9003819
TI  - Appendiceal spirochetosis.
AB  - Appendiceal spirochetosis is rarely described in the literature. We assessed the
      incidence of spirochetosis in a series of 109 appendectomies (76 adult and 33
      pediatric cases) done for either suspected acute appendicitis or as a concurrent
      procedure. Appendiceal spirochetosis was identified on hematoxylin-eosin sections
      and confirmed by Steiner and Steiner stain and ultrastructural study in two women
      and two men. One of these four patients was found to have HIV infection. The HIV
      status of the other three patients was unknown. We observed appendiceal
      spirochetosis to be an uncommon phenomenon that affects both sexes, occurring
      with or without symptoms of acute appendicitis. None of our four positive cases
      occurred in the pediatric age group.

PMID- 9003818
TI  - Inflammatory pseudotumor of the liver associated with extrahepatic infection.
AB  - We present two cases that support an infectious cause of inflammatory pseudotumor
      of the liver. Each patient had sepsis due to chronic abdominal abscesses, along
      with a liver mass. Both patients had exploratory celiotomy, and histologic
      examination of the liver mass revealed inflammatory pseudotumor of the liver.
      Evidence of a mixed bacterial/Actinomyces infection was noted in hepatic tissue
      sections in one patient, and Bacteroides caccae was cultured directly from the
      liver biopsy in the other patient. This is the first known report of bacteria
      being cultured from biopsy specimens of a hepatic pseudotumor and the only
      reported case of Actinomyces within a hepatic pseudotumor. Clinical and
      pathologic findings in these two cases indicate that an extrahepatic infectious
      source should be explored as a potential cause of inflammatory pseudotumor of the
      liver.

PMID- 9003820
TI  - Aminoglycoside levels in critically ill surgical patients: the implications of
      physiologic criteria of sepsis.
AB  - We retrospectively reviewed medical records and computerized critical care data
      for 40 consecutive critically ill surgical patients receiving "standard" doses
      (1.5 to 2.0 mg/kg loading dose and 3 to 5 mg/kg/day) of gentamicin or tobramycin
      for gram-negative infections. End points measured were serum drug levels and
      clearance of infection. Therapeutic serum aminoglycoside levels were achieved
      within 48 hours of therapy by only 7 patients (17.5%). Among the remaining 33
      patients, significantly fewer septic than nonseptic patients had clearance of
      their infection (11% vs 92%). Specific physiologic criteria of sepsis may be used
      to identify critically ill patients who will most likely benefit from aggressive
      initial aminoglycoside dosing when these drugs are used to treat gram-negative
      infections.

PMID- 9003821
TI  - Efficacy of a central venous access service.
AB  - A central venous access service (CVAS) was created in a 600-bed teaching hospital
      to do elective percutaneous central venous catheterization (PCVC) in a safe and
      expeditious manner. A vascular surgeon, physician assistants, and registered
      nurses specializing in intravenous therapy comprise the service. From November
      1990 through June 1995, the CVAS was consulted for 1,008 PCVC procedures--853
      primary insertion attempts and 155 guidewire exchanges. Various types of
      catheters were inserted for hemodialysis, fluid and medication administration,
      chemotherapy, and total parenteral nutrition. The primary insertion failure rate
      was 4% (31/853) and the major complication rate was 1% (8/853); major
      complications consisted of four pneumothoraces and four lymphocutaneous fistulae.
      Success and complication rates were superior to those previously reported for
      less experienced operators. The favorable results of this study support the
      efficacy of a CVAS.

PMID- 9003822
TI  - Modern analysis of pathologic uterine rings.
AB  - A computerized medical record search of 61,406 live births from January 1, 1990,
      through December 31, 1994, identified 14 cases of pathologic uterine rings. This
      yielded an incidence of pathologic uterine rings of 0.02% of all live births. In
      a retrospective, matched study design, three control subjects having vaginal
      delivery and three having cesarean delivery were matched with each case of
      pathologic uterine ring for age, race, parity, estimated gestational age, single
      or multiple gestation, primary or repeat cesarean section, and indication for the
      cesarean delivery. Comparison with controls who had cesarean section showed no
      significant differences in duration of labor, rupture of membranes, use of
      oxytocin, or fetal head position. Pathologic uterine rings continue to occur in
      modern obstetrics, but their reported incidence has decreased. These data suggest
      that the characteristics of parturition have no clear association with the
      formation of a pathologic uterine ring.

PMID- 9003823
TI  - Effects of cardiac rehabilitation and exercise programs on exercise capacity,
      coronary risk factors, behavior, and quality of life in patients with coronary
      artery disease.
AB  - Previous studies have indicated the benefits of cardiac rehabilitation programs
      after major coronary artery disease (CAD) events. We studied 591 consecutive
      patients from two academic institutions before and after completion of a cardiac
      rehabilitation and exercise training program to determine the effects of this
      therapy on exercise capacity, indices of obesity, plasma lipid values, behavioral
      characteristics, and quality of life parameters. After cardiac rehabilitation,
      statistically significant improvements occurred in exercise capacity (+33%),
      percent body fat (-6%), body mass index (-1%), HDL-C (+5%), triglycerides (-9%),
      LDL-C/HDL-C (-6%), anxiety score (-39%), depression score (-35%), somatization
      score (-37%), and in all parameters of quality of life studied (total +14%).
      These data further support the ability of cardiac rehabilitation and exercise
      training programs to improve exercise capacity, plasma lipid values, obesity
      indices, behavioral characteristics, and quality of life parameters in a large
      cohort of patients who have had major CAD events.

PMID- 9003824
TI  - Elective versus emergency cesarean hysterectomy on a teaching service--1981 to
      1991.
AB  - We compared the differences in morbidity of elective and emergency cesarean
      hysterectomy (CH) in a training program. Records of patients who had elective or
      emergency CH were reviewed for information reflecting perioperative morbidity and
      fetal outcome. Eighty-eight CHs were elective and 18 were emergencies. Compared
      to emergency CHs, operative time for elective CHs was 30 minutes less,
      intraoperative blood loss was 700 mL lower, less postoperative blood replacement
      was needed, and hospital stay was 3.5 days shorter. Emergency CH had nearly twice
      the frequency of postoperative febrile morbidity and a three-times-higher rate of
      morbidity due to other causes. CHs were done at a gestational age of 36 or more
      weeks in 81.6% of elective cases, compared to only 50% of emergency cases. Mean
      birth weight of newborns delivered electively was 900 g higher, and Apgar scores
      were better. These data show that CHs done by house staff in training have a
      significantly lower complication rate when the operations are elective rather
      than emergent.

PMID- 9003825
TI  - Beachfront screening for skin cancer in Texas Gulf coast surfers.
AB  - Skin cancer screening programs may attract the "worried well," while those at
      greatest risk for skin cancer are less likely to attend. Our purpose was to
      compare the results of skin cancer screening examinations between persons
      participating in the 1992 American Academy of Dermatology-sponsored free skin
      cancer screening and surfers participating in a free beachfront skin cancer
      screening held in conjunction with a regional surfing competition. The hypothesis
      was that screening an at-risk population (ie, surfers) would be more productive
      in terms of incidence of clinically diagnosed malignant skin lesions. Surfers
      were significantly younger and predominantly male. The incidence of basal cell
      carcinoma was significantly greater in the surfing population than in the self
      selected population with similar ages. This study indicates that directed skin
      cancer screening of an at-risk population was more productive in finding skin
      cancer than screening of a self-selected population. Future efforts to identify
      individuals with skin cancer should be broadened to include high-risk populations
      such as daytime outdoor athletes and high-risk occupational groups, since they
      may not be reached by current screening efforts.

PMID- 9003826
TI  - Extrarenal retroperitoneal angiomyolipoma.
AB  - We describe a case of angiomyolipoma arising in the retroperitoneum and review
      other reported cases of extrarenal angiomyolipoma. We review the histologic
      characteristics of angiomyolipoma and describe our diagnostic evaluation. This
      case is the fifth reported occurrence of extrarenal retroperitoneal
      angiomyolipoma. In our case, as in the others, the correct diagnosis was made
      only after laparotomy, despite a number of preoperative imaging studies. Careful
      exploration should, in the future, result in more renal-sparing approaches.

PMID- 9003827
TI  - Guillain-Barre syndrome and cytomegalovirus infection during pregnancy.
AB  - We report a case of Guillain-Barre syndrome and associated cytomegalovirus
      infection during pregnancy. A 15-year-old black adolescent had progressive
      ascending paralysis and vague sensory symptoms during week 10 of her first
      pregnancy. Diagnosis of Guillain-Barre syndrome was confirmed by
      electrophysiologic findings consistent with acute demyelinating
      polyradiculoneuropathy. A mild elevation of anti-GM1 antibodies was also
      detected. The patient improved with plasmapheresis treatment; however, fetal
      death occurred 10 weeks later. Cytomegalovirus placentitis was confirmed
      histologically. Acute demyelinating polyneuropathy during pregnancy warrants
      consideration of a concomitant, primary maternal and fetal cytomegalovirus
      infection.

PMID- 9003828
TI  - Myelomatous pleural effusion.
AB  - Malignant pleural effusions due to multiple myeloma are rare. Effusion in such
      patients is usually due to congestive heart failure or another process. Malignant
      myeloma cells identified in cytologic examination of the pleural fluid or by
      pleural biopsy establish the diagnosis of a myelomatous effusion. This finding
      portends a poor prognosis and death usually within 4 months.

PMID- 9003829
TI  - Pseudo-Gaucher's cells in association with common acute lymphoblastic leukemia.
AB  - Gaucher-like cells were found in the bone marrow and liver of an Omani teenager
      who had common acute lymphoblastic leukemia (cALL) confirmed on peripheral blood
      analysis by the presence of CD10 antigen. Leukocytic or fibroblastic beta
      glucocerebrosidase enzyme activity was not measured, but other biochemical data
      and features of bone marrow on electron microscopy were not indicative of genuine
      type 1 Gaucher's disease. To our knowledge, this is the first report of pseudo
      Gaucher's cells in association with cALL.

PMID- 9003830
TI  - Noninvasive positive pressure ventilation.
AB  - Noninvasive positive pressure ventilation (NPPV) has been used in treatment of a
      variety of clinical conditions, including acute respiratory failure (ARF) due to
      status asthmaticus. We present the case of a patient admitted with acute
      exacerbation of asthma who had ARF and required mechanical ventilation. After
      extubation, he had respiratory distress and was successfully treated with NPPV.
      NPPV was continued for approximately 24 hours, with clinical improvement and
      avoidance of reintubation. Despite the benefits of NPPV (ie, improved patient
      comfort, reduced need for sedation, and avoidance of complications associated
      with mechanical ventilation), it has not been widely used. Understanding the
      clinical indications for and limitations of NPPV allows successful use of this
      noninvasive method of mechanical ventilation.

PMID- 9003831
TI  - Perineal hernia repair using gracilis myocutaneous flap.
AB  - Perineal hernia formation is an infrequent but well-recognized complication of
      major pelvic surgery. Various methods of perineal reconstruction have been
      reported. This report describes one technique of perineal hernia repair using a
      unilateral gracilis myocutaneous flap. The gracilis myocutaneous flap provides
      well-vascularized tissue that is useful in many situations requiring
      reconstruction of the pelvis and perineum, especially when the area has been
      irradiated.

PMID- 9003832
TI  - Pulmonary nodules due to Toxocara canis infection in an immunocompetent adult.
AB  - Infection with Toxocara canis is well described in the pediatric literature but
      is reported less commonly in adults. We report a case of T canis infection
      manifested as abdominal pain with diarrhea, eosinophilia, and diffuse
      noncavitating nodules in an immunocompetent adult.

PMID- 9003834
TI  - An unusual complication of diabetes mellitus: the zebra that became a horse.
AB  - A 41-year-old black woman with a history of well-controlled, insulin-dependent
      diabetes mellitus was in her usual state of relatively good health when she had
      acute onset of right upper quadrant and epigastric abdominal pain, nausea, and
      vomiting. Physical examination and laboratory evaluation revealed
      gastrointestinal hemorrhage, decreased mental status, and acidemia, and emergency
      exploratory laparotomy elucidated ischemic bowel, of which 90 cm was resected.
      Postoperatively, the patient had cardiac arrest and could not be resuscitated.
      Autopsy was remarkable for mesenteric venous thrombosis and pylethrombosis, with
      ischemic necrosis of bowel and passive hyperemia. The arterial side of the
      cardiovascular system was relatively unaffected. Although arterial vascular
      complications of diabetes mellitus are well known, venous complications are less
      well described.

PMID- 9003835
TI  - Esophageal atresia in an in vitro fertilization pregnancy.
AB  - Major congenital anomalies occur in approximately 4% of the newborn population.
      Although this risk is apparently the same for in vitro fertilization (IVF)
      pregnancies, couples having assisted reproduction therapy should receive
      appropriate genetic counseling, because coincidental maloccurrences are often
      erroneously linked to the technology. We report a case of newborn esophageal
      atresia with tracheoesophageal fistula occurring in an IVF pregnancy. Physicians
      are encouraged to educate all prospective parents regarding the rate of
      congenital anomalies in the general population so that they have realistic
      expectations concerning newborn outcome.

PMID- 9003836
TI  - Elevated tumor-associated antigen CA 19-9 in a patient with an enlarged pancreas:
      does it always imply malignancy?
AB  - Carbohydrate antigen 19-9 (CA 19-9) has been used as a serum tumor marker for
      adenocarcinoma of the upper gastrointestinal tract, particularly primary
      adenocarcinoma of the pancreas. This tumor marker has also been used to
      differentiate benign from malignant diseases of the pancreas. However,
      significant elevations of CA 19-9 levels in the absence of pancreatic malignancy
      have also been reported. This case illustrates a marked elevation of CA 19-9 due
      to an infectious process in a patient with a pancreatic mass suggestive of
      malignancy.

PMID- 9003833
TI  - Idiopathic midesophageal stricture: a new cause of dysphagia in a patient with
      AIDS.
AB  - A number of disorders may result in the complaint of dysphagia in HIV-infected
      patients. These include fungal, viral, bacterial, parasitic, medication-induced,
      and idiopathic lesions in the esophagus. In the current case, a 32-year-old man
      with advanced HIV infection had recurrent bouts of esophageal stricture. No ulcer
      was associated with this stricture. No infectious causes of the stricture could
      be determined. The patient required multiple upper endoscopies and dilatations
      for treatment of this stricture and subsequently had a food impaction. This is
      the first case in the medical literature of an idiopathic stricture in the middle
      portion of the esophagus in an HIV-infected patient. We postulate that this
      lesion may have been caused by the patient's medications. Esophageal strictures
      should be considered in HIV-infected patients with severe dysphagia or food-bolus
      impactions of the esophagus.

PMID- 9003837
TI  - Rapid progression of acquired amegakaryocytic thrombocytopenia to aplastic
      anemia.
AB  - Acquired amegakaryocytic thrombocytopenia is a rare disorder characterized by
      severe thrombocytopenia and selective, marked decrease or absence of
      megakaryocytes. Although immunosuppressive therapy (prednisone and/or
      antithymocyte globulin) has been shown to induce remissions in a subset of
      patients, most patients do not respond, and progression to aplastic anemia occurs
      in some cases. We report a case of acquired amegakaryocytic thrombocytopenia
      which, despite aggressive immunosuppressive treatment, rapidly progressed to
      aplastic anemia. Clinical, laboratory, and immunologic features of our patient's
      case are described and compared to those of the previously reported six cases
      that progressed from amegakaryocytic thrombocytopenia to aplastic anemia.

PMID- 9003838
TI  - Atracurium and persistent paralysis.

PMID- 9003839
TI  - Narcan therapy.

PMID- 9003841
TI  - Methotrexate therapy for chronic sarcoidosis: is the therapeutic index
      acceptable?

PMID- 9003840
TI  - Oral dexamethasone therapy for chronic immune thrombocytopenic purpura: home run
      or base hit?

PMID- 9003842
TI  - "Awaiting an eruption": predictors of acne vulgaris.

PMID- 9003844
TI  - Assessment of inflammatory bowel disease.

PMID- 9003843
TI  - Attention deficit hyperactivity disorder: a disease or a symptom complex?

PMID- 9003845
TI  - A trial of high-dose dexamethasone therapy for chronic idiopathic
      thrombocytopenic purpura in childhood.
AB  - OBJECTIVE: To determine the efficacy of high-dose dexamethasone in chronic
      idiopathic thrombocytopenic purpura of childhood. METHODS: Seventeen patients
      entered the protocol. Dexamethasone was to be given orally in two divided doses
      at a dosage of 20 mg/m2 for 4 consecutive days every 28 days for six courses.
      RESULTS: One month after the end of the sixth course, six patients (35%) had
      platelet values within the normal range. One year later, five patients (29%)
      still have normal platelet values. Five patients discontinued treatment before
      completion because of lack of response and in one case for important side
      effects. Duration of the disease before treatment was inversely correlated with
      response to dexamethasone: 5 of 10 patients who had had thrombocytopenia for 30
      months or less went into remission, as opposed to none of the seven who had been
      sick for a longer period (p = 0.04). Side effects included fatigue or
      irritability, anxiety, abdominal pain, striae, hirsutism, acne, and weight gain.
      CONCLUSIONS: Contrary to what is observed in adults, in our patients pulsed
      dexamethasone therapy did not prove to be uniformly effective. However, in view
      of its effectiveness in a third of the patients, acceptable side effects, and low
      cost, we believe that this treatment could be considered in patients with chronic
      idiopathic thrombocytopenic purpura who do not tolerate the disease well,
      especially if no more than 3 years have elapsed since diagnosis. Larger studies
      will be necessary to define which patients will respond to this type of therapy.

PMID- 9003846
TI  - Platelet and immune responses to oral cyclic dexamethasone therapy in childhood
      chronic immune thrombocytopenic purpura.
AB  - OBJECTIVE: To examine the effectiveness of cyclic oral high-dose (HD)
      dexamethasone therapy in pediatric patients with chronic immune thrombocytopenic
      purpura (ITP), which has been reported to cause complete remission in adults with
      chronic ITP. STUDY DESIGN: Eleven children with primary chronic ITP, with a
      median disease duration of 28 months (range, 6 to 120 months), were treated with
      cycles of HD dexamethasone therapy. RESULTS: Excellent short-term responses
      (initial platelet counts < or = 50 x 10(9)/L, increasing to > 100 x 10(9)/L
      within 72 hours of completion of an HD dexamethasone cycle) were observed in 78%
      of 41 cycles. Long-term effects include one complete response (platelet count >
      or = 150 x 10(9)/L) and three partial responses (platelet count > or = 50 and <
      150 x 10(9)/L) in 11 children followed for 6 or more months after completing
      cyclic HD dexamethasone therapy. Because side effects were substantial, three
      children did not complete their sixth treatment cycle. At day 6 of treatment, B
      lymphocytes were significantly increased (p = 0.005). CONCLUSIONS: Dexamethasone,
      given orally in high doses, is an effective drug in achieving short-term platelet
      responses, but it induced long-term remissions in fewer than half of the children
      with well-established chronic ITP. Its effect on B lymphocytes requires further
      elucidation. A prospective, controlled study will be needed to establish whether
      cyclic HD dexamethasone therapy can alter the natural history of children with
      early chronic ITP and thus avoid splenectomy.

PMID- 9003847
TI  - Low-dose methotrexate therapy for childhood sarcoidosis.
AB  - OBJECTIVE: To evaluate the effectiveness of low oral doses of methotrexate as a
      steroid-sparing agent in children with sarcoidosis. STUDY DESIGN: An open-label,
      noncontrolled trial. Methotrexate was administered orally at a single weekly dose
      of 10 to 15 mg/m2. Duration of therapy was open ended, but patients received
      treatment for a minimum of 6 months to be considered as having completed the
      study. RESULTS: Seven children with biopsy-proven sarcoidosis completed the
      study. The mean dose of prednisone was successfully tapered from 49 mg/day (1.3
      mg/kg) to 18 mg/day (0.5 mg/kg) after 3 months of methotrexate therapy and to 9.9
      (0.2 mg/kg) and 7.3 mg/day (0.1 mg/kg) after 6 months and at the end of the
      follow-up period, respectively. Other clinical and laboratory parameters improved
      significantly after methotrexate therapy was started. There was significant
      clinical improvement, as confirmed by the reduction of the clinical severity
      score from 8 +/- 1.1 to 0.8 +/- 0.5 point after 3 months of methotrexate therapy,
      and to 0.7 and 0.5 +/- 0.3 point after 6 months and at the end of the follow-up,
      respectively. Laboratory measurements revealed marked improvement, as reflected
      by a significant reduction in the erythrocyte sedimentation rate and an increase
      of hemoglobin values. The mean serum angiotensin-converting enzyme activity
      dropped significantly. No adverse side effects were noted with methotrexate
      therapy. CONCLUSION: Our study demonstrated that low-dose oral methotrexate
      therapy was effective and safe and had steroid-sparing properties in seven
      children with sarcoidosis.

PMID- 9003848
TI  - Predictors of severity of acne vulgaris in young adolescent girls: results of a
      five-year longitudinal study.
AB  - OBJECTIVES: The objectives of this study were to determine which factors in early
      pubertal girls might be predictive of later, severe facial acne. STUDY DESIGN:
      The study was a 5-year longitudinal cohort study, with yearly visits from 1987
      through 1991, in a volunteer sample of 439 black and 432 white fourth- and fifth
      grade girls with consent from their legal guardians. The subjects were recruited
      from public and parochial schools in Cincinnati, Ohio. The degree of facial acne
      was classified annually as mild, moderate, or severe. Blood samples were obtained
      at the first, third, and fifth years of the study. Using the acne status during
      the fifth year of the study as the outcome variable, we determined the
      contributions from the prior acne status and the serum levels of
      dehydroepiandrosterone sulfate (DHEAS), testosterone, free testosterone (FT),
      estradiol (E2), progesterone, and testosterone-estrogen binding globulin (TEBG)
      and compared the results at various ages and at times before and after menarche.
      RESULTS: No racial differences in acne or hormone levels were found. There was a
      progressive increase in the number of acne lesions with age and maturation. The
      girls exhibited many more comedonal than inflammatory acne lesions, regardless of
      age. The girls in whom severe acne developed by the fifth year of the study had
      significantly more comedones and inflammatory lesions than girls with mild or
      moderate acne, as early as age 10 years, approximately 2 h years before menarche,
      a time when their degree of acne was mild. Girls with mild comedonal acne had
      significantly later onset of menarche (12.5 compared with 12.2 years) than girls
      with severe comedonal acne. Girls in whom severe comedonal acne developed had
      significantly higher levels of serum DHEAS and, in a longitudinal analysis,
      somewhat higher levels of testosterone and FT in comparison with girls who had
      mild or moderate comedonal acne. Serum E2, testosterone/E2, progesterone, and
      TEBG values were no different in girls with severe compared with mild or moderate
      comedonal acne. CONCLUSIONS: The early development of comedonal acne may be one
      of the best predictors of later, more severe disease. The adrenal hormone DHEAS
      appears to play an important role in the initiation of acne. DHEAS, testosterone,
      and FT are associated with the perpetuation of severe comedonal acne. Early
      recognition of young girls at risk of having severe comedonal acne may enable the
      clinician to intervene and thus prevent unwanted sequelae.

PMID- 9003849
TI  - Epilepsy and attention deficit hyperactivity disorder: is methylphenidate safe
      and effective?
AB  - OBJECTIVE: To study the safety and efficacy of methylphenidate in children with
      the dual diagnosis of epilepsy and attention deficit hyperactivity disorder
      (ADHD). STUDY DESIGN: Thirty children, aged 6.4 to 16.4 years, with epilepsy and
      ADHD were studied during a 4-month period. During the initial 2 months of the
      study, the children were treated with antiepileptic drugs (AEDs) only, and for
      the remaining 2 months, methylphenidate was added at a morning dose of 0.3 mg/kg.
      They underwent neurologic assessment, brain computed tomography, IQ testing, and
      assessment with the Childhood Behavior Checklist at baseline before
      methylphenidate therapy. Electroencephalography, AED determinations, and the
      continuous-performance task (CPT) test were done at baseline and after 2 months
      of methylphenidate therapy. A double-blind, crossover design was used to compare
      the effects of methylphenidate versus placebo on an electroencephalogram, AED
      levels, and the CPT. On the 2 days of testing, the child received AEDs and a
      capsule containing either placebo or methylphenidate. RESULTS: None of the 25
      children of this sample who were seizure free had attacks while taking
      methylphenidate. Of the 5 children with seizures, 3 had an increase in attacks,
      whereas the other 2 showed no change or a reduction. There were no significant
      changes in AED levels or electroencephalographic findings. Methylphenidate
      benefited 70% of children according to parental report; methylphenidate also
      enhanced performance on the CPT. Side effects of methylphenidate were mild and
      transient. CONCLUSION: Methylphenidate is effective in treating children with
      epilepsy and ADHD and safe in children who are seizure free. Caution is warranted
      for those still having seizures while receiving AED therapy.

PMID- 9003850
TI  - Hyperglycemia during childhood diarrhea.
AB  - OBJECTIVE: To determine the cause of hyperglycemia in childhood diarrhea.
      METHODS: During an 8-month period, patients admitted to a diarrhea treatment
      center in Bangladesh had their blood glucose concentrations determined. Sixteen
      patients aged 2 to 10 years with hyperglycemia (blood glucose concentration >10.0
      mmol/L) and 20 patients in the same age group with a normal blood glucose
      concentration (3.3 to 9.0 mmol/L) had blood samples obtained on admission and 4
      and 24 hours later for determination of glucoregulatory hormones and
      gluconeogenic substrates. RESULTS: Prevalence of hyperglycemia among patients
      aged 2 to 10 years was 9.4%. Compared with the normoglycemic patients,
      hyperglycemic patients more often had severe dehydration (100% versus 10%, p
      <0.001), infection with Vibrio cholerae 0 1 or toxigenic Escherichia coli (94% vs
      25%, p <0.001), and had similar duration of fasting (16 vs 14 hours, p = 0.677).
      Concentrations of epinephrine (7.15 vs 2.00 micromol/L), norepinephrine (10.35 vs
      3.50 micromol/L), cortisol (1.38 vs 0.82 micromol/L), glucagon (36 vs 14 pmol/L),
      and C-peptide (1.22 vs 0.35 nmol/L) were all significantly (p < or = 0.014)
      higher in patients with hyperglycemia than in normoglycemic patients.
      CONCLUSIONS: The development of hyperglycemia in diarrhea is caused by a stress
      response to hypovolemia.

PMID- 9003851
TI  - Ursodeoxycholic acid improves the hepatic metabolism of essential fatty acids and
      retinol in children with cystic fibrosis.
AB  - OBJECTIVE: Several clinical trials of ursodeoxycholic acid (UDCA) have shown
      improvement of liver-function test results in cystic fibrosis (CF) with liver
      disease; however, there is no evidence that the long-term course will be
      affected. In view of the observations that UDCA can change the lipid profile and
      that patients with CF and liver disease are more likely to have essential fatty
      acid (EFA) deficiency, we elected to examine changes in the lipid profile and in
      the status of fat-soluble vitamins in response to UDCA. METHODS: Nineteen
      children with CF and liver dysfunction were recruited for a double-blind,
      crossover study of 1 year's duration, followed by treatment of the entire group.
      UDCA was administered at a dosage of 15 mg/kg per day, which, in the absence of a
      50% decrease of alanine transaminase or aspartate transaminase or both within 2
      months, was increased to 30 mg/kg per day. RESULTS: At entry, all patients had
      biochemical evidence of EFA deficiency. The lipid profiles during an average
      period of 25 months of follow-up showed a significant decrease in triglycerides
      (p <0.002), cholesterol (p <0.02), and total fatty acids (p <0.006). In addition,
      UDCA therapy led to an improvement in EFA status, as indicated by an increase (p
      <0.05) in the n-6 fatty acid concentration and a reduction (p <0.04) in the 20:3n
      9/20:4n-6 fatty acid ratio. Although no change in vitamin E levels was observed,
      retinol metabolism was altered. There was an increase (p <0.02) in the
      unesterified retinol/retinol binding protein molar ratio in the absence of a
      difference in retinol binding protein concentration. Furthermore, retinyl esters,
      which normally account for less than 3% of circulating retinol, decreased (p
      <0.05) from 13.7% +/- 3.6% to 8.1% +/- 1.7%. CONCLUSIONS: This study confirms
      that UDCA alters lipoprotein metabolism and shows that it improves the EFA and
      retinol status of patients with CF and liver disease.

PMID- 9003852
TI  - Primary bronchomalacia in infants and children.
AB  - OBJECTIVE: To determine the natural history of primary bronchomalacia in infants
      and children. STUDY DESIGN: Retrospective chart review and follow-up telephone
      questionnaire of 17 patients with bronchoscopically confirmed primary
      bronchomalacia. RESULTS: All patients had initial symptoms within the first 6
      months of life, and all patients were thought by their primary care physicians to
      have reactive airways disease. In no patient was the diagnosis of bronchomalacia
      considered before referral to our center. All patients had a harsh, monophonic
      wheeze loudest over the central airway and intermittently present between
      illnesses. All 17 patients had bronchomalacia of the left main-stem bronchus; two
      had mild tracheomalacia associated with the bronchomalacia; and one had bilateral
      bronchomalacia. One patient had associated laryngomalacia. Twenty-five percent of
      our patients had reactive airway disease in addition to bronchomalacia. With
      growth, all patients have shown a gradual improvement and a cessation of daily
      symptoms. All three patients older than the age of 5 years report limitation of
      vigorous exercise. CONCLUSIONS: Bronchomalacia should be considered in the
      differential diagnosis of the persistently wheezing infant and should be
      evaluated appropriately. More severe forms of bronchomalacia appear to predispose
      patients to exercise limitation later in life, which suggests that the lesion
      does not completely resolve with growth.

PMID- 9003854
TI  - T-lymphocyte subsets in West African children: impact of age, sex, and season.
AB  - OBJECTIVE: There has been no reference material for T-lymphocyte subsets for
      normal children in developing countries. We therefore used T-lymphocyte subset
      determinations among children in three different studies in Guinea-Bissau to
      construct age-related reference material and to examine possible determinants of
      T-lymphocyte subset levels. METHODS: A total of 803 healthy West African children
      younger than 6 years were included in the three community studies of T-lymphocyte
      subsets among twins and singletons, after measles infection and after measles
      immunization. We used the immunoalkaline phosphatase method to determine T
      lymphocyte subsets. RESULTS: We found differences by age, sex, and season,
      whereas there were no significant differences by birth order, twinning, or ethnic
      group. The CD4+ percentage declined from birth to age 2 years, at which time it
      started to increase to higher levels at age 4 to 5 years. The CD8+ percentage
      increased gradually from early infancy to age 2 to 4 years. The leukocyte count
      peaked at age 12 to 23 months and declined thereafter, whereas the lymphocyte
      percentage peaked at age 1 to 5 months and declined gradually thereafter.
      Compared with dry-season results, the lymphocyte percentage, the absolute
      lymphocyte count, the absolute CD4+ T-lymphocyte count, and the CD4+/CD8+ ratio
      were significantly lower during the rainy season, whereas the CD8+ percentage was
      increased during the rainy season. Girls had higher CD4+/CD8+ ratios and lower
      CD8+ percentages than did boys. CONCLUSIONS: Compared with the limited data on T
      lymphocyte subsets available from healthy children in developed countries,
      Guinean children have markedly lower CD4+ percentages and CD4+/CD8+ ratios and
      higher lymphocyte percentages during the first 2 years of life, when the pressure
      of infections is particularly high in Africa.

PMID- 9003853
TI  - Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency with the G1528C
      mutation: clinical presentation of thirteen patients.
AB  - Long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase is one of three enzyme
      activities of the mitochondrial trifunctional protein. We report the clinical
      findings of 13 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase
      deficiency. At presentation the patients had had hypoglycemia, cardiomyopathy,
      muscle hypotonia, and hepatomegaly during the first 2 years of life. Seven
      patients had recurrent metabolic crises, and six patients had a steadily
      progressive course. Two patients had cholestatic liver disease, which is uncommon
      in beta-oxidation defects. One patient had peripheral neuropathy, and six
      patients had retinopathy with focal pigmentary aggregations or retinal
      hypopigmentation. All patients were homozygous for the common mutation G1528C.
      However, the enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase activities of the
      mitochondrial trifunctional protein were variably decreased in skin fibroblasts.
      Dicarboxylic aciduria was detected in 9 of 10 patients, and most patients had
      lactic acidosis, increased serum creatine kinase activities, and low serum
      carnitine concentration. Neuroradiologically there was bilateral periventricular
      or focal cortical lesions in three patients, and brain atrophy in one. Only one
      patient, who has had dietary treatment for 9 years, is alive at the age of 14
      years; all others died before they were 2 years of age. Recognition of the
      clinical features of long-chain 3-hydroxyacyl-CoA deficiency is important for the
      early institution of dietary management, which may alter the otherwise invariably
      poor prognosis.

PMID- 9003855
TI  - Evaluation of a new method of administration of the iron chelating agent
      deferoxamine.
AB  - We compared the effectiveness of deferoxamine administered by twice-daily
      subcutaneous injections with conventional administration by prolonged
      subcutaneous infusion in 20 patients with thalassemia. Urinary iron excretion was
      comparable with the two methods but decreased significantly when the total daily
      dose was administered as a single injection. Local reactions were similar with
      infusion and injection. Subcutaneous injections of deferoxamine may be considered
      as an alternative to conventional infusions.

PMID- 9003856
TI  - Treatment of apneustic respiratory disturbance with a serotonin-receptor agonist.
AB  - Apneusis is a disturbance of respiratory rhythm characterized by severely
      prolonged inspiratory effort. It may occur after damage to the respiratory
      network within the lower brain stem and pons from an overdose of central nervous
      system depressants, blockade of glutamate receptors, asphyxia, hypoxia, or
      ischemia. Experimental studies conducted on laboratory mammals, such as
      anesthetized cats and rats, suggest that apneusis results mostly from depression
      of glutamatergic synaptic processes that are necessary for activation of
      inhibitory mechanisms that terminate inspiration. The impairment of synaptic
      transmission leads to prolonged inspiratory efforts and apneustic discharges of
      brainstem respiratory neurons. Apneustic patterns can be consistently converted
      to normal by administration of serotonin type 1A (5-HT1A) receptor agonists. This
      observation encouraged a treatment of severe apneusis with buspirone, an agonist
      for 5-HT1A receptors, in a child after neurosurgery for an astrocytoma in the
      pons and medulla oblongata. Oral administration of buspirone produced a prompt
      and highly effective remission of apneusis without side effects. Treatment with 5
      HT1A agonists, therefore, might offer a novel and effective pharmacotherapy
      against apneustic disturbances of breathing.

PMID- 9003857
TI  - Effects of intrauterine growth retardation in premature infants on early
      childhood growth.
AB  - OBJECTIVE: To evaluate in preterm infants the role of intrauterine growth
      retardation and infant body proportionality on subsequent childhood growth.
      METHODS: Preterm infants (818) prospectively enrolled in the Infant Health and
      Development Program were studied from birth to 36 months of corrected age.
      Weights and lengths were recorded at eight intervals. Growth parameters were
      compared in preterm infants with differing body symmetry at birth, defined by
      length-for-age and weight-for-age. Infants with both low length-for-age and low
      weight-for-age at birth were categorized as symmetrically growth retarded, and
      infants with normal length-for-age and low weight-for-age were categorized as
      asymmetrically growth retarded. RESULTS: Infants born with low length-for-age
      demonstrated increased growth velocity until 8 months of corrected age (p
      <0.001). However, infants born with low weight-for-age demonstrated decreased
      weight-gain velocity compared with preterm infants with appropriate weight for
      gestational age (AGA) until 40 weeks of corrected age (p <0.001). Heights and
      weights of infants with either symmetric or asymmetric intrauterine growth
      retardation remained significantly retarded compared with AGA preterm patients
      and the National Child Health Survey (NCHS) reference population (p <0.001).
      Infants born short but with normal weight did not significantly differ from AGA
      preterm infants in either weight or length at 36 months of corrected age. Preterm
      infants with both symmetric and asymmetric growth retardation demonstrated
      limited catch-up growth in weight until age 4 months and then paralleled the AGA
      preterm patients and the NCHS reference population. Very low birth weight (< or =
      1250 gm), gestational age, and a broad-based day-care intervention did not
      influence growth outcome after control for the presence of intrauterine growth
      retardation. CONCLUSIONS: Preterm infants with both symmetric and asymmetric
      intrauterine growth retardation demonstrate limited catch-up growth. Intrauterine
      growth deficits persist into early childhood.

PMID- 9003858
TI  - Does vitamin C cause hemolysis in premature newborn infants? Results of a
      multicenter double-blind, randomized, controlled trial.
AB  - OBJECTIVE: We tested the hypothesis that vitamin C supplementation of premature
      neonates is associated with hemolysis. STUDY DESIGN: A double-blind, randomized,
      controlled trial of vitamin C supplementation (50 mg/day) was undertaken in
      premature neonates (birth weight, 1000 to 1500 gm). Infants were randomly
      assigned to receive vitamin C (Ce-Vi-Sol) (n = 32) or placebo (n = 24) for 14
      days. Twenty-three subjects per group were required to detect a difference of 1
      SD in corrected carboxyhemoglobin values (alpha = 0.05, beta = 0.10). RESULTS:
      Day 14 vitamin C levels were lower in control subjects than in supplemented
      neonates (62 +/- 24 vs 125 +/- 62 micromol/L, p = 0.005). There was no difference
      in corrected blood carboxyhemoglogin concentrations (0.72 +/- 0.44 vs 0.72 +/-
      0.23%; p = 0.95), other parameters of hemolysis, weight gain, blood sampled,
      presumed septic episodes, necrotizing enterocolitis, feeding intolerance, or
      transfusion. On day 14, bilirubin values were higher in control subjects than in
      the supplemented group (77 +/- 37 vs 55 +/- 33 micromol/L; p = 0.04). When a
      distant outlier in the nonsupplemented group was excluded (163 micromol/L),
      statistical significance was lost (73 +/- 32 vs 55 +/- 33 micromol/L; p = 0.09).
      CONCLUSION: Oral supplementation of premature infants with vitamin C is not
      associated with evidence of increased erythrocyte destruction,
      hyperbilirubinemia, or other morbidity.

PMID- 9003859
TI  - Milk type during mixed feeding: contribution to serum cholesterol ester fatty
      acids in late infancy.
AB  - OBJECTIVE: To evaluate the contribution of the type of milk on serum cholesterol
      ester fatty acids in infants receiving mixed feeding, we analyzed 3-day dietary
      records and serum cholesterol ester fatty acid composition of 397 seven-month-old
      infants. STUDY DESIGN: The infants received, in addition to solid food, only one
      type of milk: human milk (n = 218), a ready-to-use liquid formula (n = 139), a
      powdered formula (n = 33), or soy formula (n = 7). RESULTS: Mean fat intakes were
      low and varied from 28% to 31% of energy; the milks provided 43% to 64% of the
      fat. The mean polyunsaturated/saturated fat ratios of solid foods were from 0.52
      to 0.63 and of milks from 0.20 to 0.45. Breast-fed infants' relative serum
      linoleic acid (18:2n-6) concentration was low (51.2%), whereas infants fed liquid
      formula had low serum oleic acid (18:1n-9) in accordance with low oleic acid
      content in that formula. The breast-fed infants had markedly higher serum
      concentrations of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3)
      than the infants fed any of the formulas. CONCLUSION: The typical fatty acid
      patterns of breast- or formula-fed infants were still evident in 7-month-old
      infants who already received 60% to 70% of their energy from solid food. Marked
      differences were seen also in the relative concentrations of docosahexaenoic acid
      and arachidonic acid despite their small contribution in cholesterol esters.

PMID- 9003860
TI  - Maturation of motility and motor inhibition in rapid-eye-movement sleep.
AB  - OBJECTIVE: To describe the age-related changes in the number of movements in
      rapid eye movement (REM) sleep, and to quantify the functional maturation of
      motor inhibition. STUDY DESIGN: Gross movements, phasic mentalis muscle activity
      (PMMA), and a new index that expressed the shortness of PMMA (the proportion of
      short PMMA among all PMMA) were examined cross-sectionally in 87 healthy children
      from premature babies to preadolescents by means of a single (all-night)
      polysomnography. RESULTS: The incidence of gross movements and long PMMA
      decreased with age, whereas that of short PMMA increased with age. The new index
      exhibited an age-related increase, with the highest correlation with age among
      sleep parameters examined, and reached an adult level after 6 years of age.
      CONCLUSION: We found that the age-related reduction of PMMA duration, which was
      expressed by a new index, occurred in parallel with the maturation of the
      inhibitory system that is tonically activated during REM sleep. We named this
      index the tonic inhibition index and concluded that the neuronal system involved
      in motor inhibition during REM sleep was still maturing during early childhood.
      We propose the tonic inhibition index as a useful quantitative indicator for the
      maturity of the inhibitory system.

PMID- 9003861
TI  - Prenatal care and infant lead exposure.
AB  - OBJECTIVE: The objective of the study was to determine the relation between
      prenatal care of mothers and blood lead concentrations in their offspring in the
      first year of life. METHODS: A retrospective survey was conducted of 200
      predominantly black infants between the ages of 6 and 22 months (mean age, 13.4
      months). The infants had been screened for the first time since birth at the
      Charleston County (South Carolina) Health Department. They resided in a
      neighborhood with the highest prevalence of lead poisoning in Charleston.
      Prenatal care use data were obtained after matching birth records with lead
      screening records. RESULTS: Seventy-three infants (37%) had blood lead levels
      0.48 micromol/L (> or = 10 microg/dl) or higher. Adequacy of prenatal care,
      defined by the Modified Kessner Index, showed 11% with intensive care (26% of
      these with high lead levels), 39% with adequate care (35% high blood lead
      levels), 35% with intermediate care (40% with high blood lead levels), 13% with
      inadequate care (42% with high blood lead levels), and 2% with no prenatal care
      (25% with high blood lead levels). With the exception of the small group with no
      prenatal care (n = 4), the proportion of infants with a high blood lead level was
      inversely proportional to the level of care. The logistic regression model that
      best fit the data included age at screen for lead and birth weight. Low birth
      weight babies (<2500 gm) were more likely to have a high blood lead level at
      primary screen than babies who were heavier at birth (odds ratio, 2.60; p =
      0.04), and the older the baby at screening, the greater the likelihood of a high
      blood lead level (odds ratio, 1.23; p = 0.01). There was a trend for black
      infants to have a high blood lead level more often than white infants (odds
      ratio, 3.05; p = 0.06). CONCLUSIONS: Less than adequate use of prenatal care may
      reflect an increase in risk factors contributing to lead exposure in infancy. Low
      birth weight also was related to high blood lead levels. Further studies are
      required to differentiate among several hypotheses for this effect. Intrauterine
      lead exposure, which is known to reduce birth weight, may contribute to measured
      blood lead levels at first screen. Alternatively, low birth weight may increase
      lead absorption and retention in infancy or may increase risk of lead exposure.

PMID- 9003862
TI  - Improved precision of newborn screening for congenital adrenal hyperplasia using
      weight-adjusted criteria for 17-hydroxyprogesterone levels.
AB  - OBJECTIVE: To evaluate the efficacy and efficiency of weight-adjusted threshold
      levels for 17-hydroxyprogesterone (17-OHP) in screening newborn infants for 21
      hydroxylase deficiency-congenital adrenal hyperplasia (21-OH-D-CAH). DESIGN:
      Analysis of the number of false-positive reports and diagnoses in infants, of 21
      OH-D-CAH with the use of two strategies. Before October 1993, separate criteria
      for definite abnormal 17-OHP levels were established and implemented for 41,846
      infants on the basis of birth weight: either less than 2200 gm (17-OHP level, 90
      ng/ml) or 2200 gm or more (40 ng/ml). To reduce the burden of follow-up testing
      in low birth weight infants, criteria for definite abnormal 17-OHP results were
      statistically determined for four, rather than two, birth weight divisions: 1299
      gm or less (17-OHP level > or = 165 ng/ml), 1300 to 1600 gm (> or = 135 ng/ml),
      1700 to 2200 gm (> or = 90 ng/ml), and more than 2200 gm (> or = 40 ng/ml). These
      criteria were applied to the next 149,684 infants screened, and rates of false
      positive test results and of false-positive diagnoses of 21-OH-D-CAH were
      compared. RESULTS: Before implementation of four-tiered weight-adjusted 17-OHP
      criteria, 205 definite abnormal reports yielded four confirmed cases of 21-OH-D
      CAH (positive predictive value = 2%; incidence of 21-OH-D-CAH = 1 in 10,461).
      With the revised criteria, 61 of 149,684 infants had definite abnormal results
      and 14 cases of 21-OH-D-CAH were confirmed (positive predictive value, 20%;
      incidence of 21-OH-D-CAH, 1 in 10,692). No undetected severe cases of 21-OH-D-CAH
      have been subsequently reported. CONCLUSIONS: Weight-adjusted criteria for 17-OHP
      levels in screening for 21 -OH-D-CAH markedly reduced the number of false
      positive results requiring immediate follow-up testing, particularly among low
      birth weight infants. Increased specificity afforded by these criteria was not
      accompanied by diminished sensitivity in detecting severe cases. Long-term follow
      up of this screened cohort will determine whether the goals of newborn screening
      for 21-OH-D-CAH are adequately and efficiently fulfilled by this approach.

PMID- 9003863
TI  - Vomiting after mild head injury is related to migraine.
AB  - OBJECTIVE: To determine whether vomiting after mild head injury in children is
      related to migraine and to identify predictors of vomiting after head injury.
      METHODS: A series of consecutive children admitted to the observation unit of an
      emergency department after mild head injury was identified by chart review. A
      telephone interview with the parents or child or both was then conducted by using
      a structured questionnaire. RESULTS: Of 47 eligible children with acute head
      injury, 44 (94%) were contacted. The mean age at head injury was 7.4 years.
      Twenty-nine children (66%) vomited after the head injury. The likelihood of
      vomiting was increased if the child had a history of recurrent headache (p =
      0.05). If the headaches were migrainous, the likelihood of vomiting increased
      further (p <0.002). All 15 children with a history of motion sickness vomited
      after the head injury. Family history of migraine, particularly maternal (n =
      21), also predicted recurrent vomiting (p <0.001). If more than one of these
      predictive variables was present, the likelihood of vomiting was 100%.
      CONCLUSIONS: History of motion sickness, migraine headaches, and family history
      of migraine are highly predictive of vomiting after a mild head injury.

PMID- 9003865
TI  - Ultrasonographic assessment of inflammatory bowel disease in children: comparison
      with ileocolonoscopy.
AB  - OBJECTIVES: To determine the feasibility and value of transabdominal
      ultrasonography of the terminal ileum and colon of children with inflammatory
      bowel disease (IBD) and to compare the findings with those of ileocolonoscopy.
      STUDY DESIGN: Thirty-eight patients ranging in age from 4 to 18 years who
      underwent ileocolonoscopy for management of IBD or for diagnosis were studied
      prospectively. Twenty-one patients had Crohn disease, nine had ulcerative
      colitis, and eight served as control subjects. Transabdominal ultrasonography was
      performed on the day before ileocolonoscopy. Ultrasonographic findings were
      compared with the results of ileocolonoscopy, used as the reference method.
      RESULTS: Peristalsis was recorded in all segments of the control subjects; the
      thickness of the terminal ileum was always less than 2.5 mm, and that of the
      large bowel, 2 mm or less. In the two patient subgroups, the thickness range of
      affected ileal and colonic segments was similar, but values were significantly
      different from those of the control subjects (chi-square test, p <0.0001). The
      overall sensitivity of the method was 88%, and the specificity, 93%. CONCLUSION:
      Transabdominal ultrasonography should prove to be a useful clinical and
      investigational technique, although further studies are needed to assess its
      value in the treatment of children with IBD.

PMID- 9003864
TI  - Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency
      responsive to riboflavin.
AB  - Deficiency of complex I (reduced nicotinamide adenine dinucleotide dehydrogenase
      ubiquinone oxidoreductase) of the mitochondrial respiratory chain may be seen as
      a pure myopathy or as a neuromuscular disorder at presentation. Efficacy of long-
      term therapy for these disorders is yet to be established. We report the case of
      a female patient with complex I deficiency and skeletal myopathy, who has had a
      sustained clinical response to riboflavin during 3 years of therapy. Molecular
      studies found no mutations in the putative flavin mononucleotide binding site in
      the 51 kd subunit of complex I, but a T-to-C transition at nucleotide 3250 in the
      mitochondrial DNA tRNA(Leu(UUR)) gene was identified. This mutation has been
      reported in one other family in that five members had fatigue with or without
      muscle weakness. There were also five cases of unexplained infant deaths in that
      family and two cases in the family reported here. Riboflavin therapy should be
      attempted in all patients with complex I deficiency when the clinical
      presentation is one of isolated skeletal myopathy.

PMID- 9003866
TI  - Point-of-care glucose testing in the neonatal intensive care unit is facilitated
      by the use of the Ames Glucometer Elite electrochemical glucose meter.
AB  - OBJECTIVE: To evaluate the Ames Glucometer Elite glucose meter for use in point
      of-care glucose testing in the neonatal intensive care unit. METHODS: An
      important part of our quality control program involves a weekly comparison of
      glucose values obtained with each of the seven Elite analyzers and the Beckman
      CX7 analyzer located in the central laboratory. Each "split" sample involves
      measurement of the glucose by using the Elite analyzer in a sample of blood
      obtained from a heel stick at the bedside, followed by bleeding ("milking") 150
      to 200 microl (4 to 5 drops) of blood into a heparinized microcontainer. This
      process should take no longer than 1 to 2 minutes, whereupon the microcontainer
      is placed on ice and sent to the laboratory. The values obtained were compared by
      regression analysis. Imprecision of the Elite meter was estimated at four levels
      of blood glucose concentration and on a normal-level quality control sample used
      for a period of 4 months. RESULTS: Regression analysis between the glucose values
      obtained on the Elite meter and the CX7 meter revealed r = 0.93, p less than
      0.0001, n = 188, Sy/x = 0.59 mmol/L, intercept = 0.47 +/- 0.14 mmol/L (1 SEM),
      and slope = 0.91 +/- 0.028 (1 SEM). When we switched to on-ice delivery of split
      samples to reduce metabolic activity during transport of the specimens to the
      laboratory, scatter about the regression line was decreased and the Sy/x was
      reduced to 0.45 mmol/L. Before the on-ice delivery of split samples, 24% of the
      Elite analyzer's results differed from those of the CX7 analyzer by more than
      15%, whereas only 8% differed from those of the CX7 meter by more than 15% after
      on-ice delivery of split samples. Of 30 samples read as "Lo" by the Elite meter,
      29 were less than 2.2 mmol/L on the CX7 meter, whereas only 1 was 2.2 mmol/L. The
      coefficients of variation taken as a measure of imprecision were less than 5% for
      the normal-level aqueous control and less than 5% for four heel-stick blood
      glucose levels. CONCLUSIONS: The Ames Glucometer Elite analyzer can be used with
      confidence in measuring heel-stick blood glucose concentrations at the bedside in
      the neonatal intensive care unit. Hypoglycemic blood samples are reliably
      detected. As with adults, meticulous technique should be followed to prevent
      filling defects, and all split samples should be analyzed promptly on the CX7
      analyzer, with delivery to the laboratory on ice. Unlike previous generations of
      glucometers, the Elite meter has been well accepted by the neonatal nursing
      staff.

PMID- 9003867
TI  - Precocious puberty in two children with neurofibromatosis type I in the absence
      of optic chiasmal glioma.
AB  - A girl aged 5 years and a boy aged 8 years with neurofibromatosis type I had
      clinical and biochemical evidence of central precocious puberty. Magnetic
      resonance imaging on two occasions in each patient failed to demonstrate any
      abnormality of the optic tracts or optic chiasm.

PMID- 9003868
TI  - Urinary nitrite versus nitrate excretion in children.

PMID- 9003869
TI  - Hypouricemia and molybdenum-cofactor deficiency.

PMID- 9003870
TI  - Hyponatremia caused by a reset osmostat.

PMID- 9003871
TI  - Continuous versus intermittent feeding for low birth weight neonates.

PMID- 9003873
TI  - Cisapride-induced prolonged QT interval: too much of a good thing!

PMID- 9003872
TI  - Cisapride high dosage and long QT interval.

PMID- 9003874
TI  - Predictors of bacterial infection in neonates.

PMID- 9003875
TI  - Misdiagnosis of acute angle closure glaucoma.
AB  - When acute glaucoma presents in its classical form, the diagnosis is fairly
      simple to make. However, atypical presentations are not uncommon and the
      diagnosis can be missed. This inevitably leads to a delay in treatment which can
      permanently compromise visual function. We have studied which doctors are most
      likely to make a misdiagnosis and calculated the resulting delay in treatment.
      All patients with acute glaucoma attending Whipps Cross eye unit between 1991 and
      1994 were identified and their notes obtained. Thirty-eight patients were found
      to have a had diagnosis of acute closed angle glaucoma. In only 39.5% was the
      diagnosis correctly made by the referring practitioner and a misdiagnosis
      resulted in a mean delay of treatment of 5.8 days. General practitioners were the
      most likely group to have difficulty making the diagnosis, while casualty
      officers were most likely to make the correct diagnosis. Because acute glaucoma
      can present without its typical features, there needs to be a high index of
      suspicion for this diagnosis. This diagnosis does not require expensive equipment
      or a high level of training--all our patients had a significant reduction in
      vision. Any patient who has a red eye and a subjective reduction in vision should
      be referred to an ophthalmologist the same day.

PMID- 9003877
TI  - Effect of ageing upon warfarin dose requirements: a longitudinal study.
AB  - This longitudinal study was designed to establish the rate of age-related change
      in warfarin dose requirements. Warfarin dosage was recorded retrospectively in
      104 patients who had been stabilized on warfarin for a median period of 10 years
      (range 6-24 years) for prophylaxis of thromboembolic disease. There was a
      significant negative correlation between dosage and age at the start of therapy
      (p = 0.002, r = -0.30). Warfarin requirements fell over time, dosage difference
      being significantly correlated with age difference (p = 0.01, r = 0.25). Use of
      regression equation derived from these data suggests a 21% fall in warfarin
      requirements in this population over a 15-year period. The relationship between
      change in warfarin dose requirements and ageing established in this longitudinal
      study is in good agreement with that established by cross-sectional studies,
      suggesting that no major birth cohort effect is influencing requirements in our
      warfarin-treated population.

PMID- 9003876
TI  - Topical beta-blockade with intrinsic sympathomimetic activity offers no advantage
      for the respiratory and cardiovascular function of elderly people.
AB  - Topical therapy with beta-antagonists, such as timolol, may cause unrecognized
      impairment of respiratory and cardiovascular function in elderly people. Beta
      antagonists with intrinsic sympathomimetic or cardioselective properties, such as
      carteolol or betaxolol, may cause less impairment. In a randomized, double-masked
      study of glaucoma patients, over 60 years of age, without history of bronchospasm
      and who were using timolol (0.5%), 60 patients were allocated to betaxolol (0.5%)
      or carteolol (2%) or continued timolol (0.5%) treatment. Spirometry, pulse and
      blood pressure were measured on enrollment and after 4 weeks. In the timolol and
      carteolol groups there were no significant changes in mean spirometric values.
      Changing to betaxolol improved mean peak flow (PF) by 9.1%, from 310 to 3411/min
      (p < 0.05) and forced expiratory volume in 1 second (FEV1) by 9.4%, from 1.74 to
      1.861 (p < 0.05). Differences in the changes in PF and FEV1 between betaxolol and
      timolol as well as betaxolol and carteolol groups were statistically significant
      (p < 0.05). Twenty-one per cent of those allocated to betaxolol showed clinically
      significant improvement in FEV1. There was no change in pulse or blood pressure
      when carteolol was substituted for timolol but an increase of 10 beats per minute
      (p < 0.05) in mean resting pulse in the betaxolol group. Therapy with
      cardioselective beta-blockade may offer significant advantages in respiratory
      function for elderly people with glaucoma over non-selective drugs, even if they
      have sympathomimetic activity.

PMID- 9003878
TI  - Changes in autonomic function with age: a study of pupillary kinetics in healthy
      young and old people.
AB  - The object of the study was to compare resting pupil diameter in darkness and
      light, and the pupillary darkness and light reflexes between a group of young and
      elderly healthy subjects. Twelve young (eight men, four women; median age 19.5
      years) and 14 elderly subjects (six men, eight women; median age 69 years)
      participated. Pupil diameter was monitored with an infra-red television
      pupillometer. Resting pupil size was measured in light (16 and 32 Cd m-2) and in
      darkness. The darkness reflex was elicited by switching off the ambient
      illumination (16 Cd m-2) for 1 s. The light reflex was elicited in darkness by
      short (200 ms) pulses of green (peak wavelength 565 nm) light at four ascending
      stimulus intensities (8.5 x 10(-3), 7.0 x 10(-2), 0.43 and 1.84 mW cm-2). The
      amplitude (mm) and maximum velocity (mm s-1) of the darkness reflex and the
      latency (ms), amplitude (mm), maximum constriction velocity (mm s-1) and 75%
      recovery time (s) of the light reflex were measured. The resting pupil diameter
      was found to be smaller in the elderly group at all three illumination levels (p
      = 0.001). The amplitude and maximum dilatation velocity of the darkness reflex
      were smaller for the elderly group (p = 0.001). The amplitude of the light reflex
      at the three highest light intensities and maximum constriction velocity at all
      light intensities were smaller in the elderly group (p = 0.002). Seventy-five per
      cent recovery time was longer in the elderly group (p = 0.02). There was no
      difference in the latency of the light reflex response between the two groups.
      The reduced pupil size, diminished darkness reflex amplitude and velocity, and
      prolonged recovery time of light reflex are consistent with sympathetic deficit
      in old age. Although the reductions in light reflex amplitude and constriction
      velocity in the elderly group at first sight would indicate a parasympathetic
      deficit in old age, they are more likely to be secondary to the grossly
      diminished pupil size.

PMID- 9003880
TI  - The effect of white matter low attenuation on cognitive performance in dementia
      of the Alzheimer type.
AB  - The effect of leukoaraiosis or white matter low attenuation (WMLA) on cognitive
      function is not fully understood. We compared the neuropsychological performance
      of 37 Alzheimer's disease patients with WMLA on CT brain scans with a similar
      group of 31 Alzheimer's disease patients with no evidence of white matter
      lesions. Patients with WMLA performed significantly worse on tests of
      visuospatial function (Cube Analysis test, p = 0.004), and cognitive speed
      (Kenrick Digit Copying test, p = 0.05) compared to those with no visible white
      matter lesions. Patients with widespread WMLA performed generally worse in tests
      of cognitive function than those with frontal or a mixture of frontal and
      occipital WMLA. This was most significant in the areas of attention (forward
      digit span, p = 0.003), visual recognition (p = 0.004), and cognitive speed (p =
      0.03). There is an association between impaired cognitive performance and the
      presence of WMLA in Alzheimer's disease patients, with WMLA probably contributing
      to the cognitive impairment. This is most evident in patients with widespread
      white matter lesions.

PMID- 9003879
TI  - A mental-functional risk score for prediction of hip fracture.
AB  - We examined the apparent value of questions of functional status and mental score
      in determining the risk of hip fracture from a large retrospective case--control
      study undertaken in six countries. Of nine questions utilized in 75% of the MEDOS
      study population, four questions were found to be statistically significant and
      independently related to the risk of hip fracture. From this an additive score
      was devised with three points for not being able to wash or dress, six points for
      not knowing one's age, and ten points for not knowing the day of the week, which
      gave a gradient of risk of 5.7 when categorized into quartiles. Similar gradients
      of risk were observed in all countries. A less than perfect score was associated
      with a specificity of 79% and sensitivity of 46%, comparable to the power of bone
      mineral density measurements. The risk factor score accounted only partially for
      the increase in risk associated with dementia, cardiovascular accidents and
      parkinsonism. We conclude that the steep gradient of risk associated with this
      simple score should be evaluated prospectively.

PMID- 9003881
TI  - Low blood pressure is not an independent determinant of survival in an elderly
      population.
AB  - The object of the study was to determine whether the increased mortality
      associated with low blood pressure in elderly people arises because of the
      adverse effects of hypotension or because of confounding variables. A community
      sample of 782 people aged 70 years and older was followed for 3 years. Blood
      pressure measurements were taken on initial assessment and hypotension was
      defined separately for systolic and diastolic pressures as a pressure less than
      the tenth percentile for the sample (systolic < or = 122 mmHg, diastolic < or =
      68 mmHg). After 3 years 135 participants had died and of these 31 had low
      systolic or diastolic blood pressure at baseline. Low diastolic pressure was
      associated with an increased mortality over the 3 years (hazard ratio 1.85, 95%
      Confidence Interval 1.18-2.91). This increase in risk was explained by
      confounding variables. Low systolic pressure was not associated with increased
      mortality. The increased mortality of those with low blood pressure is explained
      by concurrent illness.

PMID- 9003882
TI  - Nutritional supplementation in elderly medical in-patients: a double-blind
      placebo-controlled trial.
AB  - The aim of this study was to assess the effect of vitamin and/or glucose energy
      supplementation in elderly medical patients on an intention-to-treat basis. One
      hundred and six elderly medical in-patients were entered into a double-bind
      placebo-controlled factorial trial of glucose energy and vitamin supplementation.
      Supplementation was given for 1 month. This trial was designed to detect a > 2 kg
      increase in weight and > 3 g/l increase in serum albumin between active and
      placebo supplementation in 100 patients with 90% power (p < 0.05). Other outcome
      measures included changes in Barthel activities of daily living, length of stay,
      and mental test score (MTS). No interaction between vitamin and glucose
      supplementation was demonstrated. Active energy supplementation with glucose
      alone was associated with a +0.6 kg change in weight and +0.7 g/l change in
      albumin [95% confidence interval (CI) -0.8, +2.0 and -1.3, +2.8, respectively].
      The respective changes for active vitamin supplementation were -0.6 kg for weight
      and +0.5 g/l for albumin (95% CI -2.1, +0.8 and -1.5, +2.6, respectively). There
      were no significant differences in mental test score, Barthel score, or length of
      stay between the two groups. Compliance with the glucose energy supplementation
      was poor with only one-third of patients consuming more than 50% of the offered
      drink. We conclude that the giving of glucose alone and/or vitamin
      supplementation in elderly patient is of no benefit on an intention-to-treat
      basis.

PMID- 9003883
TI  - Factors affecting contrasting results between self-reported and performance-based
      levels of physical limitation.
AB  - We have examined the role of socio-demographic variables, cognitive and affective
      functioning, and personality in discrepancies between performance-based and self
      report measures within three domains of physical limitations: motor functioning,
      hearing and vision. Data are drawn from a community-based sample of 624 persons
      of 57 years of age and older. The strength of the association between self
      reported and performance-based levels of physical limitations is moderate. Socio
      demographic variables and levels of cognitive functioning explained some of the
      discrepancies between self-reported and performance-based vision. Within the
      domains of motor functioning and hearing, discrepancies were substantially
      influenced by affective functioning and personality. The discrepancies may
      reflect bias in perception or true variation in the effect of limitations on
      daily functioning. Both self-report and performance-based measures seem to
      complement each other in providing useful information about physical limitations.

PMID- 9003884
TI  - A pilot study of the introduction of audit into nursing homes.
AB  - In 1993, all 37 private nursing homes in Mid-Staffordshire were invited to take
      part in this study, and 16 agreed. Over 1 year, a nurse audit facilitator visited
      these homes to teach staff, and stimulate and assist with audit projects. At the
      beginning and end of the 12-month period, the residents were assessed by
      administered questionnaires and by the short Geriatric Depression Scale. Thirteen
      of the 16 homes undertook at least one audit project during the study (ten of
      these had never previously carried out audit). Ten homes made at least one major
      procedural change during the study. Of the 570 residents of the 16 homes, 138
      answered both questionnaires. The main reasons for non-inclusion were poor mental
      and physical conditions. Satisfaction levels improved significantly in six out of
      the 11 aspects of care studied. The mean Geriatric Depression Score in these 138
      residents fell from 4.73 at the start, to 4.25 at the end of the study (p =
      0.02). The fall in the mean score was significantly greater in the ten homes that
      had made at least one major change (from 4.40 to 3.81) than in the six homes that
      had made no major change (from 5.33 to 5.17). The introduction of audit into co
      operative private nursing homes is associated with improvements in the standards
      of care, but it is uncertain whether this is a direct consequence of the audit
      carried out, or is due to the non-specific effects of an outside assessor
      visiting the homes. There is a need for methods of assessment that can be applied
      to higher proportions of nursing home residents.

PMID- 9003886
TI  - Predicting disability in stroke--a critical review of the literature.
AB  - Research articles on the prognosis of stroke patients were analysed to identify
      studies that met sound methodological principles of prognostic research as well
      as to identify variables capable of predicting functional outcome (ADL) after
      stroke. Data sources comprised a computer-aided search of published prognostic
      studies and references to literature used in prognostic studies. Seventy-eight
      studies were tested for adherence to the following key methodological criteria:
      reliability and validity of measurement instruments used to assess dependent and
      independent variables; inclusion of an inception cohort; adequate and uniform end
      point of observation; control for drop-outs during period of observation;
      statistical testing of presumed relationship between dependent and independent
      variables; sufficient sample size in relation to number of determinants; control
      for multicollinearity; specification of patient characteristics (i.e. age, type,
      recurrent stroke and localization of stroke); description of interfering
      treatment effects during the period of observation, and cross-validation of the
      prediction model in a second independent group of patients. Only three studies
      satisfied nine out 11 criteria and ten studies eight criteria for the
      determination of valid prognostic research. The results of these studies indicate
      that the following variables are valid predictors for functional recovery after
      stroke: age; previous stroke; urinary continence; consciousness at onset;
      disorientation in time and place; severity of paralysis; sitting balance;
      admission ADL score; level of social support and metabolic rate of glucose
      outside the infarct area in hypertensive patients. This study supports the
      general opinion that not only are differences in objectives and heterogeneity in
      stroke patients responsible for the lack of accuracy in predicting functional
      outcome, but also the methodological flaws in published prognostic research.

PMID- 9003885
TI  - Early T-cell activation in elderly humans.
AB  - This study characterizes the early steps of T lymphocyte activation in elderly
      subjects. The expression of CD69, the earliest inducible antigen which appears
      with T lymphocyte activation, was assessed in T cells cultured with medium, anti
      CD3 or PMA. The proliferative responses of T cells stimulated through CD69 and
      CD3 pathways were also studied. Donors included 31 healthy elderly [age mean (SD)
      80(8) years] and 33 healthy young [age 30(5) years] subjects. In elderly people,
      the expression of CD69 was lower in T cells cultured with medium [3.4% (1.65-5.9;
      25-75 percentiles) vs. 10% (6-18), p < 0.0003] and anti-CD3 activated [28.1%
      (16.5-53.8) vs. 79.5% (73-89), p < 0.0002] T cells. With PMA at 10 ng/ml, CD69
      expression was higher in both groups of T cells, though still lower in the aged
      [84.5% (70.9-94.9) vs. 99% (65.7-100), p = 0.051]. CD69 T cells expression was
      equal in both groups with 2 ng/ml of PMA, but the co-stimulatory responses to
      CD69 under these conditions and in the presence of anti-CD3 were lower in the
      aged (16914 vs. 28904 cpm, p < 0.02) and (6944 vs. 14370 cpm, p < 0.02)
      respectively. Aged T cells failed to express CD25 at the same levels of young T
      cells when stimulated with CD69. These results suggests an age-associated defect
      in the very early steps of T lymphocyte activation that might influence later
      stages of lymphocyte function. An alteration in the transmission of the
      activation signal from the cell surface to protein kinase C may play a primary
      role in this defect.

PMID- 9003887
TI  - Prescribing practice and policy for hypnotics: a model of pharmacy audit.
AB  - A problem of overprescribing of hypnotic medication ('sleeping tablets') was
      identified and quantified within a department of health care for older people in
      a district general hospital. Data on the volume of prescribing were obtained from
      computerized pharmacy records, and this information was supplemented by a
      retrospective survey of case notes of 100 patients. Sixty per cent of patients
      were prescribed a hypnotic at some stage during their hospital stay. Twelve per
      cent were prescribed a sleeping tablet on admission on an 'as required' basis but
      never took this medication, suggesting that such prescribing was becoming
      routine. As part of an ongoing pharmacy audit within the department, a policy was
      implemented to try to improve prescribing habits. Following this, hypnotic
      prescribing fell, with the average monthly number of sleeping tablets prescribed
      falling from 2392 to 734. A further survey of 100 case notes showed overall
      prescribing had fallen to 25%, although 2% were still prescribed a hypnotic on
      admission but never took it.

PMID- 9003888
TI  - Outcome in patients who require a gastrostomy after stroke.

PMID- 9003889
TI  - Absorbable polyglycolide devices in trauma and bone surgery.
AB  - Poly(glycolic acid) or polyglycolide (PGA) is a polymer of glycolic acid.
      Glycolic acid is produced during normal body metabolism and is known as
      hydroxyacetic acid. Strong implants can be manufactured from this polymer with a
      self-reinforcing (SR) technique and used in the treatment of fractures and
      osteotomies. Since 1984, SR-PGA implants have been used routinely in our hospital
      for internal fixation of bone fractures. These implants were studied extensively
      in experimental animals and proved biocompatible. In 1.7% of human cases, sinus
      formation may develop after the use of these implants, which does not disturb
      healing. Use of these absorbable implants is justified as it obviates the need
      for a second operation for implant removal and avoids the risks associated with
      biostable implants.

PMID- 9003891
TI  - Analysis of the leaching and toxicity of new amine activators for the curing of
      acrylic bone cements and composites.
AB  - The comparative reactivity of new tertiary amine activators with the basic
      chemical structure of N,N-dimethyl-4-toluidine, but reduced toxicity, is
      analysed. The leaching of the amine compounds from cured cements was studied by
      analysis of the concentration of the corresponding amine in a physiological
      saline solution after 3 months of immersion, giving lower values for the new
      amine compounds as compared to N,N-dimethyl-4-toluidine. The acute toxicity was
      determined by intravenous injection of saline solutions of the corresponding
      chlorhydrates in mice and the cytotoxicity by the evolution of specific culture
      media. The results obtained demonstrate a lower acute toxicity and cytotoxicity
      of the new activators, even with a noticeable antiseptic action, which makes
      these materials very interesting from a practical point of view as activators of
      the curing process of acrylic bone cements for orthopaedic surgery and dentistry.

PMID- 9003890
TI  - Heterogeneous iron-containing fluoridated apatites.
AB  - The iron-containing fluoridated hydroxyapatites Fe-FeFAp and FeF-FeAp were
      synthesized heterogeneously in the presence of ferrous ions at 80 degrees C and
      pH 7.4 in two different types of solution, i.e. fluoride-free solution during the
      initial half of the experimental period and fluoride-containing solution during
      the second half, in the latter of which the fluoride concentration was equivalent
      to that of fluorapatite. Another experiment was carried out under the opposite
      conditions. The total fluoride contents of both heterogeneous iron-containing
      fluoridated apatites were almost the same (0.83 +/- 0.01 and 0.89 +/- 0.02 mmol g
      1, respectively). Their X-ray diffraction patterns were not significantly
      different. However, scanning electron microscopy showed that Fe-FeFAp was
      composed of clusters of rod-like crystals and FeF-FeAp of bundles of many thin
      needle-like crystals. Energy dispersive spectroscopy coupled with scanning
      electron microscopy estimated that the fluoride intensity of Fe-FeFAp was higher
      than that of FeF-FeAp. The apparent solubility of the former (Ca = 8.83 +/- 0.20,
      P = 4.27 +/- 0.13 mmol l-1) was less than that of the latter (Ca = 10.8 +/- 0.4,
      P = 5.56 +/- 0.09 mmol l-1) at 37 degrees C and pH 4.0. These results suggest
      that two different types of heterogeneous iron-containing fluoridated apatites
      may be formed.

PMID- 9003892
TI  - Histomorphometric analysis of the response of rat tibiae to shape memory alloy
      (nitinol).
AB  - The bone reaction to nitinol (Ni-Ti), a metal with shape memory, and other
      materials inserted transcortically and extending into the medullary canal of rat
      tibiae was quantitatively assessed using an image processing system. The
      materials examined were implants, all of the same shape and size, composed of
      nitinol, pure titanium (Ti), anodic oxidized Ti (AO-Ti), a titanium alloy (Ti-6Al
      4V) and pure nickel (Ni). While the other four implant materials were
      progressively encapsulated with bone tissues, Ni was encapsulated with connective
      tissues through the 168-day experimental period, and the Ni implants showed no
      bone contact at any time during the experimental period. Histometric analysis
      revealed no significant difference among the tissue reactions to Ti, AO-Ti and Ti
      6Al-4V, but Ni-Ti implants showed significantly (P < 0.01) lower percentage bone
      contact and bone contact area than any of the other titanium or titanium alloy
      materials.

PMID- 9003894
TI  - In vivo tissue compatibility of two radio-opaque polymeric biomaterials.
AB  - Polymeric biomaterials featuring intrinsic radio-opacity continue to attract
      considerable scientific attention. This work focusses on two polymers that
      contain covalently bound iodine, rendering the materials radio-opaque. The first
      material is hard, transparent and glass-like, and consists of methyl
      methacrylate, 2-(2'-iodobenzoyl)-ethyl methacrylate (1) and 2-hydroxyethyl
      methacrylate (HEMA), in the molar ratio 65:20:15, respectively. The second
      material is a cross-linked hydrophilic network, consisting of HEMA and 1, in the
      molar ratio 80:20, respectively. Both materials were characterized by means of
      different physico-chemical techniques, including magic-angle-spinning solid state
      NMR spectroscopy, infrared spectroscopy and differential scanning calorimetry.
      Moreover, both materials were implanted subcutaneously in rats for 24 days. Upon
      explanation and histological examination, it appeared that both materials were
      well tolerated. No tissue necrosis, abscess formation or inflammation were
      observed. The samples were found to be surrounded by a vascularized capsule
      consisting of connective tissue cells. The results reveal excellent tissue
      compatibility for both materials. This is an important observation, since tissue
      compatibility is absolutely necessary for the applications which are foreseen for
      this type of radio-opaque biomaterials.

PMID- 9003893
TI  - Nanotechnology for biomaterials engineering: structural characterization of
      amphiphilic polymeric nanoparticles by 1H NMR spectroscopy.
AB  - Nanoparticles composed of diblock poly(D,L-lactide-co-glycolide)-poly(ethylene
      glycol) (PLGA-PEG) or a branched, multiblock PLA-(PEG)3 were prepared by the
      single emulsion technique. Results of previous studies of these nanoparticles
      suggested that their structure is of the core-corona type with a polyester core
      and an outer PEG coating. In the present study, 1H NMR spectroscopy was utilized
      to provide direct evidence of the structure of these nanoparticles suspended in
      an aqueous environment. The results confirm the existence of the core-corona
      structure under these conditions, and show that the PEG moieties extend out from
      the nanoparticle core into the aqueous environment, and exhibit chain mobility
      similar to that of PEG in solution.

PMID- 9003895
TI  - Application of macromolecular additives to reduce the hydrolytic degradation of
      polyurethanes by lysosomal enzymes.
AB  - Of the various polymers used in medical devices, polyurethanes have been
      relatively successful because of their acceptable mechanical and biological
      properties. However, over the past decade, increasing concerns have arisen in
      relation to long-term biostability of polyurethanes when exposed to the harsh
      environment of the human body. Lysosomal enzymes released from inflammatory cells
      have been proposed to be important mediators in the degradation of biomedical
      polyurethanes. In order to increase the biostability of polyurethanes to
      lysosomal enzymes, a series of surface-modifying macromolecules (SMMs) were
      synthesized in this work and then combined into a base polyurethane to reduce the
      material's susceptibility to hydrolysis. X-ray photoelectron spectroscopy (XPS)
      studies showed that the SMMs were enriched within the upper 10 nm of the surface.
      In vitro biodegradation test results indicated that the degradation of a
      polyester-urea-urethane could be inhibited by the new SMM surface. It was also
      found that different SMM formulations provided varying degrees of inhibition
      against the biodegradation of the polyester-urea-urethane. Certain formulations
      of the SMMs were shown to be physically incompatible with the polyurethane and
      distorted surface morphology to the extent that biodegradation was enhanced.

PMID- 9003896
TI  - Novel anti-calcification treatment of biological tissues by grafting of
      sulphonated poly(ethylene oxide).
AB  - Biological porcine tissue was modified by the direct coupling of sulphonated
      poly(ethylene oxide) (PEO-SO3) containing amino acid end groups after
      glutaraldehyde fixation. The calcification of the modified tissue [bioprosthetic
      tissue (BT)-PEO-SO3] and control (BT control) was investigated by in vivo rate
      subdermal, canine aorta-illiac shunt and right ventricle-pulmonary artery shunt
      implantation models. Less calcium deposition of BT-PEO-SP3 than of BT control was
      observed in in vivo tests. Such a reduced calcification of BT-PEO-SO3 can be
      explained by decreases of residual glutaraldehyde groups, a space filling effect
      and, therefore, improved biostability and synergistic blood-compatible effects of
      PEO and SO3 groups after the covalent binding of PEO-SO3 to tissue. This simple
      method can be a useful anti-calcification treatment for implantable tissue
      valves.

PMID- 9003897
TI  - Corrosion of the intra-oral magnets by multi-species biofilms in the presence and
      absence of sucrose.
AB  - The purpose of this study was to determine the corrosive effects of multi-species
      biofilms on intra-oral magnets in the presence and absence of sucrose. Using
      pooled human saliva as an inoculum, biofilms were grown on the surfaces of 90
      neodymium-iron-boron (Nd2Fe14B) magnets in a constant depth film fermentor under
      aerobic conditions at 37 degrees C. The fluid phase was a mucin-containing
      artificial saliva (delivered at a rate of 0.72/litres day-1), and, after 15 days,
      100 ml of 10% (w/v) sucrose was added (as three pulses of 33.3 ml) each day for a
      further 15 days. Six magnets with attached biofilms were removed periodically. On
      each sampling occasion the numbers of aerobes, anaerobes, streptococci,
      veillonellae and actinomyces in each biofilm, the pH of the fermentor effluent
      and the dry mass of the magnets were determined. Addition of sucrose to the
      fermentor resulted in a fall in pH (from a mean of 6.94 to a mean of 4.96), an
      increase in the proportion of streptococci and a decrease in the proportion of
      veillonellae comprising the biofilms. The decrease in mass of the magnets was 28
      fold greater in the presence of sucrose than in its absence. The results of this
      study have shown that the presence of sucrose affects the microbial composition
      of multi-species biofilms growing on Nd2Fe14B magnets and results in a marked
      increase in corrosion of the magnets.

PMID- 9003898
TI  - Changes in compressive strength on ageing in glass polyalkenoate (glass-ionomer)
      cements prepared from acrylic/maleic acid copolymers.
AB  - Previous studies have shown that glass-ionomers made from acrylic/maleic
      copolymers stored in water reach a maximum strength at about 1 week, and after 4
      months have become significantly weaker. This finding, which contrasts with the
      behaviour of glass-ionomers based on poly(acrylic acid), was originally
      attributed to hydrolytic instability. This interpretation has been tested in the
      current work. Specimens of glass-ionomer prepared from acrylic/maleic acid
      copolymer have been stored for up to 4 months in different media, namely
      deionized water, dry air and vegetable oil, then tested for compressive strength.
      Specimens were in the form of cylinders of dimensions 6 mm high x 4 mm diameter,
      and storage temperature was 37 degrees C. Data were analysed using two-way
      analysis of variance (ANOVA) and in all three media specimens became weaker at 4
      months than they had been at 1 week (P < 0.05). However, for the specimens stored
      in dry air and in water, the 1-week values were not the maximum. The fact that
      there was a loss of strength under all conditions led to the conclusion that it
      is not, after all, due to hydrolysis.

PMID- 9003900
TI  - Phagocytosis of chemically modified carbon materials.
AB  - An oxidizing treatment of carbon fibres in boiling nitric acid leads to
      significant changes in the chemical state of their surface. As a result of the
      chemical treatment on a hydrophobic carbon surface, hydrophilic domains are
      formed and phenolic, carbonyl and carboxyl groups appear. In this work the
      intensity of phagocytosis of carbon fibres obtained by carbonization of
      polyacrylonitrile was studied both for HNO3 etched and non-etched fibres. Part of
      the powdered material studied was placed in plasma before it was contacted with
      cells. To study the material, which was first placed in plasma and then contacted
      with cells, X-ray photoelectron spectroscopy and Fourier transform infrared
      spectroscopy were used. It was found that the powders made from the etched fibres
      are phagocytized more intensively. It was also found that the absorption of
      plasma proteins enhances the phagocytosis only for the fibres oxidized in HNO3
      and has no influence in the case of powders obtained from non-etched fibres.

PMID- 9003899
TI  - An investigation of the parameters influencing the bioadhesive properties of
      Myverol 18-99/water gels.
AB  - An in vitro assessment was undertaken of the parameters influencing the
      bioadhesive strength of lyotropic liquid crystalline gels formed by the
      monoglyceride blend Myverol 18-99 and water. The gels were found to bind more
      strongly to a dry Perspex surface than to moist mucosal tissue and were shown to
      be weaker bioadhesives than Carbopol 934P and sodium alginate. The works of
      adhesion and forces of detachment were independent of contact time, were reduced
      by the presence of surface water and increased with an increase in the
      compression force, suggesting that interpenetration was not the mechanism of
      bioadhesion. The bioadhesion of Myverol 18-99/water gels appeared to be due to
      secondary chemical bonds, such as van der Waals forces, but was limited by their
      cohesive strength. An in vivo gel retention assessment by gamma scintigraphy
      showed that the gels were retained within the vaginal cavity for a period of at
      least 6 h.

PMID- 9003901
TI  - Rat sciatic nerve regeneration through a micromachined silicon chip.
AB  - The capacity of regenerating nerve fibres to grow through a perforated silicon
      chip was tested using the silicone chamber model for nerve regeneration. The
      chips were fabricated as circular membranes, 4 mm in diameter, thickness 60
      microns, with a perforated area, 2 mm in diameter, in the centre. Three types of
      chips were fabricated utilizing anisotropic etching. The chips were glued with
      silicone adhesive between two halves of silicone rubber tubing (total length 8
      mm, inner diameter 1.8 mm, outer diameter 3.0 mm) which was used to bridge a 4 mm
      gap between the proximal and distal nerve stumps of a transected rat sciatic
      nerve. The capacity of regenerating nerve fibres to grow through the holes of the
      chip was analysed by light and scanning electron microscopy after 4 or 16 weeks
      of regeneration. Furthermore, the muscle contractility force of the gastrocnemius
      muscle was measured after 16 weeks of regeneration and compared as a percentage
      of the contralateral uninjured side. Nerves generated through chips with hole
      diameters of 10 or 50 microns were morphological and functional failures. The
      nerve structures distal to chips with hole diameters of 100 microns contained
      many myelinated nerve fibres in a minifascicular pattern after both 4 and 16
      weeks of regeneration. The muscle contractility force was 56% of that of
      contralateral control muscles.

PMID- 9003902
TI  - Application of the low vacuum scanning electron microscope to the study of
      biomaterials and mammalian cells.
AB  - The use of the scanning electron microscope (SEM) in 'low' (reduced) vacuum
      (lvac) mode permits observation of specimens which have not been coated with a
      conductive material such as gold or carbon. We have evaluated the use of this
      mode of observation to the study of biomaterials using the bone-substitute
      material Interpore as an example. On this material, rat bone cells were visible
      in lvac mode only in cells traversing pores, when they were readily identified by
      their cell nuclei. Rat calvarial bone examined uncoated in lvac mode showed the
      bone structure clearly through the overlying layer of osteoblast cells, which
      were subsequently revealed by gold coating. Immunogold labelling of alkaline
      phosphatase was imaged in lvac mode, following silver enhancement and carbon
      coating. These studies demonstrate the complementary use of the lvac and high
      vacuum (hvac) SEM to study material composition, the behaviour of mammalian cells
      on biomaterials and the potential use of lvac SEM to study mineralized tissues
      without removal of overlying soft tissue.

PMID- 9003903
TI  - Adhesion of Lactobacillus species in urine and phosphate buffer to silicone
      rubber and glass under flow.
AB  - Coating uroepithelial cells or catheter materials with lactobacilli has been
      shown to retard the development of a uropathogenic biofilm, with biosurfactant
      production and strong adhesion being two prerequisite properties of the
      Lactobacillus strains to be employed. In this paper, adhesion of six selected
      Lactobacillus strains to silicone rubber and glass in urine and in a phosphate
      buffer was studied using a parallel plate flow chamber. In addition, adhesive
      cell surface properties of the lactobacilli, i.e. the pH dependences of their
      zeta potentials and their hydrophobicities by water contact angles, were
      determined. L. acidophilus ATCC 4356 and L. fermentum B54 were the only strains
      showing significant adhesion to both hydrophobic silicone rubber and hydrophilic
      glass, possibly by virtue of their high cell surface hydrophobicities (water
      contact angles of 68 and 75 degrees, respectively) and small zeta potentials (
      10.0 and -8.1 mV in buffer, respectively). Both hydrophobic Lactobacillus strains
      adhered less well in urine than in buffer. The remaining Lactobacillus strains
      studied were hydrophilic, with water contact angles between 25 and 36 degrees,
      and had highly negative zeta potentials, reaching -37.7 mV in buffer. Adhesion of
      these highly negatively charged, hydrophilic strains in buffer was essentially
      absent, while for some of these strains minor adhesion in urine was observed.
      This study demonstrates that the adhesion of lactobacilli to substrata differs
      with strain hydrophobicity and charge, and that urinary components can affect the
      ability of hydrophilic Lactobacillus strains to adhere to substrata.

PMID- 9003904
TI  - Studies of the candidate genes TGFB2, MSX1, TGFA, and TGFB3 in the etiology of
      cleft lip and palate in the Philippines.
AB  - Population-based candidate-gene studies can be an effective strategy for
      identifying genes involved in the etiology of disorders where family-based
      linkage studies are compromised by lack of access to affected members, low
      penetrance, and/or genetic heterogeneity. We evaluated association data for four
      candidate genes using a population from the Philippines that is genetically
      separate from previously studied Caucasian populations. Case ascertainment was
      made possible by collaboration with Operation Smile, a volunteer medical
      organization, which facilitated identification of a large number of cases for
      study. A new allelic variant of transforming growth factor-beta 3 was identified
      to use in these studies. After exclusion of syndromic cases of cleft lip and
      palate, no evidence for association with previously reported allelic variants of
      transforming growth factor-beta 2 (TGFB2), homeobox 7 (MSX1), or transforming
      growth factor-alpha (TGFA), or with the new TGFB3 variant was detected. Previous
      association studies using Caucasian populations of nonsyndromic cleft lip and/or
      palate (CL/P) and cleft palate only (CPO) have strongly suggested a role for TGFA
      in the susceptibility of clefting in humans. Exclusion of significant association
      in a non-Caucasian population for TGFA suggests that TGFA plays less of a role
      than it does in Caucasians. This may be due to multiple or different genetic
      and/or environmental factors contributing to the etiology of this most common
      cranio-facial anomaly in the Philippine population.

PMID- 9003905
TI  - Clinical and epidemiologic studies of cleft lip and palate in the Philippines.
AB  - Clinical and epidemiologic studies of defined geographic populations can serve as
      a means of establishing data important for genetic counseling and as a first step
      in identifying strategies best suited for identification of causes. Under the
      sponsorship of Operation Smile International, clinical, genetic, and
      epidemiologic studies were carried out at six sites within the Philippines
      between 1989 and 1996. Patients who were being evaluated for surgical repair of
      craniofacial anomalies (primarily clefts of the lip and palate) were briefly
      examined for the presence of associated anomalies, and a family history was
      obtained to look for the frequency of cleft lip and palate in siblings. Birth
      records of 47,969 newborns over an 8-year period at one hospital in Bacolod City
      in the province of Negros Occidental were reviewed. Medical records of infants
      born with clefts of the lip and/or palate and other major anomalies were reviewed
      and birth prevalence rates calculated. Findings include a birth prevalence of
      1.94 per 1000 live births for cleft lip with/without palate in the Philippines.
      Recurrence rates in siblings for nonsyndromic clefts of the lip and palate were
      23 per 1000 for cleft lip with or without cleft palate, and 14 per 1000 for cleft
      palate only. The percentage of clefts associated with multiple anomalies was 21%
      at birth and 6% for individuals examined during the screening process, providing
      evidence for a high postnatal death rate. These data provide groundwork for
      additional etiologic studies including segregation analysis and molecular genetic
      studies involving linkage or association, as well as for studies of environmental
      contributions to clefting such as vitamin deficiencies. Preliminary molecular
      analysis using an association approach is reported in a companion paper. The
      findings suggest a high incidence of cleft lip and palate in native-born
      Filipinos.

PMID- 9003906
TI  - Maternal smoking and orofacial clefts.
AB  - To investigate a possible association between maternal smoking during pregnancy
      and oral clefts, a study was conducted using Swedish health registries. Infants
      with oral clefts (N = 1834) were selected among 1,002,742 infants born between
      1983 and 1992 with known smoking exposure in early pregnancy. Confounders such as
      maternal age and parity were controlled for by using the Mantel-Haenszel
      technique. A statistically significant association with maternal smoking was
      found. The odds ratio (OR) for any maternal smoking among cases of cleft lip with
      or without cleft palate [CL(P)] was 1.16 (95%Cl: 1.02-1.32). For cases of cleft
      palate alone (CP), the corresponding OR was 1.29 (95%Cl: 1.08-1.54). The results
      of the present study, based on the largest series of oral cleft cases published
      to date, indicate that cigarette smoking during pregnancy is associated with
      increased risks of CL(P) and CP.

PMID- 9003907
TI  - Gingivoperiosteoplasty and midfacial growth.
AB  - The objective of this study was to report the effect of gingivoperiosteoplasty on
      growth of the midfacial skeleton 6 years following primary surgical repair.
      Patients with complete unilateral cleft lip and palate who underwent primary
      cleft lip and nose repair with and without gingivoperiosteoplasty (GPP) were
      retrospectively compared by means of a lateral cephalogram. Mean age at the time
      of evaluation was 5.7 years. All patients were treated at the Institute of
      Reconstructive Plastic Surgery, New York University Medical Center. All surgery
      and presurgical orthopedics was performed by the same surgeon and the same
      orthodontist. Twenty-five consecutively treated patients who presented with
      complete unilateral clefts of the primary and secondary palate were included in
      the study. Of these, 20 patients were available for 6-year follow-up
      cephalometric documentation and review. All patients received preoperative
      orthopedics with passive molding appliances, followed by repair of the lip,
      alveolus, and nose in a single stage at the age of 3 months. The repair was
      performed using the rotation/advancement technique. The difference between the
      two groups was whether or not gingivoperiosteoplasty was performed. The reason
      for not performing gingivoperiosteoplasty was incomplete approximation of the
      alveolar segments usually due to a late start in beginning therapy. Lateral
      cephalograms (68.5 months post primary surgery) were obtained and traced. Cranial
      base (S-N), maxilla (ANS-PNS), and mandible (Go-Pg) were digitized for shape
      coordinate analysis. No significant difference in the mean position of ANS-PNS
      was found between groups (with or without gingivoperiosteoplasty). There was,
      however, a significant difference in the variance of position for the points ANS
      PNS between the groups (p < .002). We were unable to observe any difference
      (anteroposterior or supero-inferior) in the average position of the hard palate
      (ANS-PNS) between groups. We conclude that gingivoperiosteoplasty results in a
      more uniform position of the hard palate (ANS-PNS) relative to patients that did
      not receive gingivoperiosteoplasty. We were unable to demonstrate any clear
      impairment of maxillary growth in the patients treated with
      gingivoperiosteoplasty when compared to patients treated without
      gingivoperiosteoplasty.

PMID- 9003908
TI  - Maxillary and mandibular dental-arch dimensions and occlusion in bilateral cleft
      lip and palate patients form 3 to 17 years of age.
AB  - The aim of this study was to describe maxillary and mandibular dental-arch form
      and occlusion in bilateral cleft of the lip and palate (BCLP) from 3 to 17 years
      of age and to compare their characteristics with a normative sample. A sample of
      22 patients with BCLP was investigated, with a noncleft control sample used for
      comparison. Dental-arch dimensions were studied on dental casts. A comparison
      between both groups was made at fixed time intervals. From 9 years of age, the
      cleft sample showed a significantly smaller maxillary depth. Maxillary dental
      arch widths were also significantly smaller than in the control group over the
      whole age period. Mandibular dental-arch measurements were very similar in both
      groups, although smaller first-molar widths were noted in the BCLP group
      beginning at 12 years of age. A tendency for end-to-end occlusion was found,
      which became more clear with age and was most markedly in the canine region.

PMID- 9003909
TI  - Differentiation between cleft lip with or without cleft palate and isolated cleft
      palate using parental cephalometric parameters.
AB  - OBJECTIVE: The purpose of this study was to identify and compare lateral
      cephalometric measurements in noncleft parents of children with cleft palate (CP)
      and cleft lip (CL), and cleft lip and palate (CLP). The hypothesis was that
      discriminant analysis would enable identification of morphometric features that
      predispose to orofacial clefting and that differ for CP, CL, and CLP and are
      unevenly distributed within parental pairs. DESIGN: This was a prospective,
      parametric analysis. SETTING: The study was conducted by the Department of Dental
      Health, University of Dundee, and the Department of Statistics, University of
      Glasgow, Scotland. SUBJECTS: From a completely ascertained sample of 286 children
      with cleft lip and/or palate born in the West of Scotland between January 1,
      1980, and December 31, 1984, a sample of 83 parents of children with non
      syndromic clefts volunteered for lateral cephalometric examination. METHODS:
      Thirty-seven cranial and 99 facial landmarks were identified and 37 linear,
      angular, and area parameters were used to describe the craniofacial skeleton.
      Analysis of variance was used for a three-way comparison of CL/CLP/CP, and
      stepwise discriminant analysis was used to determine which variables discriminate
      best between cleft lip with or without cleft palate [CL(P)] and isolated cleft
      palate (CP) parents. RESULTS: There were no significant differences whatsoever in
      the craniofacial morphology between the parents of children with CL and CLP, but
      differences were found between the CL(P) and CP groups. The most significant of
      these were in mandibular length, ramus length, mandibular area, and cranial area.
      Mandibular ramus length alone discriminated between the two groups in 71.4% of CP
      and in 62.5% of CL(P) cases, while separate analysis of fathers and mothers
      showed that ramus length and cranial height together reliably distinguish between
      mothers in 75% of CP and 80% of CL(P) cases. CONCLUSIONS: Previous studies
      suggests that unaffected parents with non-syndromic children with cleft lip
      and/or palate have differences in their craniofacial morphology when compared to
      the general population. This study indicates that these morphologic features
      differ for CP and CL(P).

PMID- 9003910
TI  - Three-dimensional analysis techniques--Part 1: Three-dimensional soft-tissue
      analysis of 24 adult cleft palate patients following Le Fort I maxillary
      advancement: a preliminary report.
AB  - The three-dimensional, facial soft-tissue changes of 24 patients with various
      cleft types following transpalatal Le Fort I osteotomy were measured using laser
      scanning techniques, radial measurements, and a color millimetric scale. There
      was a varying degree of midface retrusion in the different cleft groups, and a
      very similar pattern of retrusion over the nasal complex. Each group of patients
      showed a varying degree of relapse postsurgically, but there was a failure in all
      the cleft groups to correct the lack of nasal projection.

PMID- 9003911
TI  - Three-dimensional analysis techniques--Part 2: Laser scanning: a quantitative
      three-dimensional soft-tissue analysis using a color-coding system.
AB  - New methods for measuring and averaging three-dimensional soft-tissue morphology
      and change from laser scans using a color millimetric scale are described. The
      techniques were employed to measure facial differences between a group of Class I
      skeletal males and females. The surgical change in one patient following
      bimaxillary surgery is also illustrated. The combination of the laser scanning
      technique and the new color coding system probed to be a simple, noninvasive,
      effective, and easily interpreted method for measuring three-dimensional soft
      tissue differences and change across the facial complex.

PMID- 9003912
TI  - Three-dimensional analysis techniques--Part 3: Color-coded system for three
      dimensional measurement of bone and ratio of soft tissue to bone: the analysis.
AB  - A new color-coded method of illustrating three-dimensional changes in the bone
      and the ratio of soft tissue to bone movement is described. The technique is
      illustrated by superimposing preoperative and 1-year postoperative CT scans of
      three patients following bimaxillary surgery. The method has proved to be a very
      simple, effective, and readily interpreted method of quantifying both bone and
      the ratio of movement of the overlying soft tissues across the face following
      surgery.

PMID- 9003913
TI  - Three-dimensional analysis techniques--Part 4: Three-dimensional analysis of bone
      and soft tissue to bone ratio of movements in 24 cleft palate patients following
      Le Fort I osteotomy: a preliminary report.
AB  - The three-dimensional changes in the bone and the ratio of soft tissue to bone
      movement were investigated in a group of 24 cleft palate patients following Le
      Fort I osteotomy. CT scans were taken for each patient preoperatively and 1 year
      postoperatively. The scans were superimposed, radial measurements calculated, and
      the changes illustrated by two separate color scales. In all of the groups, there
      was a fairly consistent pattern of movement over the mandible. The soft tissues
      moved in a 1.25:1 ratio over the chin and canine regions, and reduced to 1:1 over
      the body. In the maxilla, there was a 1:1 movement in the midline increasing to
      1.25:1 bilaterally over the alar bases for both the bilateral clefts and clefts
      of the secondary palate groups. In the unilateral cleft group, however, there was
      a greater degree of movement over the cleft than over the noncleft side.

PMID- 9003914
TI  - Rhinoplasty in the cleft lip patient.
AB  - Several important factors to consider in the surgical repair of the cleft lip
      nose are described: the importance of an adequate lip closure technique to ensure
      symmetry can prevent a more conspicuous deformity of the nose during growth, the
      consequences of secondary rhinoplasty in the growing nose in which the surgeon
      has to weigh the possible growth inhibition due to scar tissue against the
      possible functional and esthetic improvement, a systematic surgical approach in
      which the operative procedure is divided into different steps, and the use of
      autogenous graft material. In the evaluation of 52 cleft lip patients (5
      bilateral clefts, 47 complete unilateral clefts) who had undergone a secondary
      rhinoplasty, two specific postoperative problems were encountered: slight to
      moderate recurrence of the caudal septal deviation (in unilateral clefts) and
      restenosis of the nasal vestibule at the cleft side. Adjustment of the surgical
      technique and the use of a custom-made vestibulum device diminished these
      sequellae considerably.

PMID- 9003916
TI  - A peculiar malformation of the upper lip: report of six cases.
AB  - Six cases of a peculiar type of upper lip malformation have been observed by the
      author during the last 40 years. The malformations in this case series were
      remarkably similar, suggesting a single teratologic entity not been reported
      before. The six patients included 1-, 11-, 4-, and 6-month-old males, a 20 year
      old male, and an 11-year-old female. Each was characterized by a crooked folded
      philtrum, a flat thin vermilion region of the upper lip, and high-positioned
      ala(e), that was unilateral or bilateral. The upper median incisors were
      separated occasionally by the thick lip frenulum without marked distortion of the
      nasomaxillary framework. The author speculates that these cases exhibited some
      disturbed penetration of the lateral nasal eminence (process) to the median part
      of the nasolabial region in their early embryologic development.

PMID- 9003915
TI  - Craniofacial growth after iatrogenic cleft palate repair in a fetal ovine model.
AB  - Controversy exists over the impact of scar formation on craniofacial growth after
      cleft palate repair. The fetal ovine model presents an opportunity to study a
      group of animals with little or no scar using cephalometric studies of cranio
      facial growth after iatrogenic cleft palate repair. Grossly evident scar is
      formed in the palates of lambs repaired at 118 days or later in gestation, while
      those animals operated at 70 and 77 days' gestation exhibited no scar grossly and
      minimal scar histologically in the submucosa with normal nasal and oral mucosal
      surfaces. For this study, 15 lambs were studied: four were unoperated, three were
      operated at 70 days, one at 77 days, and seven had clefts produced and repaired
      at 118 to 133 days' gestation. The animals were euthanized at 1 month of age and
      the heads removed and frozen until analyzed. Computerized tomography of the heads
      was used to create voxel (volume pixel) data sets, and volume rendering and
      measurement software (Voxblast) was used to create a three-dimensional
      reconstruction of the skull. Palate measurements were obtained by selecting
      points on the upper deciduous premolars. A plane was set through the palate and
      upper deciduous premolars using standard points on the skull to maintain
      consistent visualization and point selection. The measurements were normalized to
      skull size measured by the distance between points on the right and left
      zygomatic bones. Using one-way analysis of variance, followed by a protected t
      test, no significant differences were found between the means of any measurement
      in the three treatment groups. Fetal palate repair, with or without scarring,
      resulted in normal craniofacial growth in the 1-month-old lamb.

PMID- 9003917
TI  - The cervical spine in Saethre-Chotzen syndrome.
AB  - Twenty patients with a diagnosis of Saethre-Chotzen syndrome had their cervical
      spine radiographs reviewed. Radiologic abnormalities including vertebral fusion
      were present in 9 of the 20 patients. Fusion of both the vertebral bodies and the
      posterior elements was noted, although the latter site was more common. C2-3 was
      the level most commonly involved, although other levels were recorded. Analysis
      of sequential radiographs in nine patients revealed evidence of progression in
      seven patients. In those studies in children aged under 2 years, only 1 of 18
      films showed evidence of fusion, while in those over 2 years of age, 10 of 12
      showed evidence of fusion. These results reveal that the incidence of cervical
      anomalies in Saethre-Chotzen syndrome is greater than that in the general
      population. There is both direct and indirect evidence that the vertebral fusions
      are progressive during childhood.

PMID- 9003920
TI  - X-ray contrast-enhancing agents.
AB  - The author argues that, whatever important and rapid developments may be taking
      place in imaging technologies, there will be a continuing need for X-ray
      enhancing agents for a considerable time to come. Areas in which there are
      current developments, such as non-ionic dimers and compact dimers, are surveyed
      and a look to a possible future of blood pool and targetted agents is offered.

PMID- 9003918
TI  - Congenital midline sinus of the upper lip: case report and review of literature.
AB  - A case report of a congenital midline sinus of the upper lip in a 5-year-old girl
      is presented. The patient complained of intermittent swelling around the frenulum
      of the upper lip. The sinus was located on the midline of the philtrum just below
      the base of the columella. Excision of the sinus tract via an intraoral approach
      gave a satisfactory result. Microscopic examination of the resected sinus
      revealed it to be lined by stratified squamous epithelium with sebaceous glands
      and hair follicles. Fifteen other cases have been reported in the English
      literature and are reviewed. There are two postulates that can account for the
      formation of the upper lip sinus based on two major theories of the development
      of the face: the fusion theory and the merging theory. However, the etiology of
      this rare congenital sinus remains obscure.

PMID- 9003921
TI  - Aspects of contrast media nephrotoxicity.

PMID- 9003922
TI  - Evaluation of the clinical safety and efficacy of iobitridol (Xenetix) in
      intravenous urography.
AB  - The aim of this study is to report on the clinical safety and diagnostic efficacy
      of iobitridol (Xenetix) in intravenous urography compared to iohexol (Omnipaque)
      or iopamidol (Iopamiro). A total of 120 patients underwent intravenous urography
      (i.v.u.); 60 received Xenetix and 60 either Omnipaque (30 patients) or Iopamiro
      (30 patients) according to the center where they were treated. Clinical safety
      was assessed by the reporting of adverse events and diagnostic efficacy was
      evaluated. Warmth sensation was the most commonly reported adverse event. Two
      cases of nausea and vomiting were reported. Concerning diagnostic efficacy, 72
      74% of the i.v.u. examinations were rated good or excellent by the physician.
      These studies confirm that Xenetix is a suitable contrast agent for i.v.u.

PMID- 9003923
TI  - MRI in children given gadodiamide injection: safety and efficacy in CNS and body
      indications.
AB  - The safety and efficacy of the MRI contrast medium gadodiamide injection
      (OMNISCAN) in children is summarised. Four open and three double-blind,
      multinational, multicentre comparative trials have been undertaken. Overall, 353
      patients (15 days to 18 years, plus one 21 years) received gadodiamide injection,
      and 128 (2-18 years) received gadopentetate dimeglumine (Magnevist),
      intravenously at 0.1 mmol/kg body weight, to aid the identification of CNS and
      body lesions. Adverse events were reported in 13 (4%) patients given gadodiamide
      injection and 8 (6%) given gadopentetate dimeglumine; few patients reported
      injection-associated discomfort. The post-contrast scan gave more diagnostic
      information in 223 (63%) patients given gadodiamide injection (CNS and body
      indications). In the comparative trials, the post-contrast scan gave more
      diagnostic information for 91 (65%) and 82 (64%) patients given gadodiamide
      injection and gadopentetate dimeglumine, respectively (CNS indications only).
      Gadodiamide injection (0.1 mmol/kg body weight) was safe and effective in
      infants, children and adolescents.

PMID- 9003924
TI  - Elimination of iomeprol by hemodialysis.
AB  - Iomeprol is commercially a relatively new type of contrast medium. There have
      been no reports concerning its dialysability and safety when administered to
      patients with end-stage renal failure undergoing regular therapeutic hemodialysis
      (HD). One hundred milliliters of iomeprol (350 mgl/ml) was injected intravenously
      at computed tomography in 10 patients suffering from chronic renal failure. HD
      was then performed within 30 min after the start of iomeprol injection. The
      duration of HD was 4 h and blood samples were taken at 15, 30 min, 1, 2 and 4 h
      after its start. Mean dialysance of urea was 176.0-182.9 ml/min, compared to
      131.4-133.3 ml/min for iomeprol. Elimination rate of iomeprol was 821.4 +/- 4.6%
      4 h after the start of HD. Two of the 10 patients had side effects. One of them
      complained of a heat sensation and the other of sneezing and rash. As 4-h HD
      effectively removed iomeprol from the body and there were no severe side effects,
      it is concluded that iomeprol is suitable for HD patients.

PMID- 9003925
TI  - Contrast agents in magnetic resonance imaging.
AB  - The author gives a brief overview of the basic mechanisms of action of contrast
      enhancing agents in MR imaging and discusses agents currently available, and
      agents soon to be available, under the classification: extra-cellular fluid space
      marker agents, hepatobiliary agents and oral agents. Likely future developments
      in these and other areas are briefly surveyed.

PMID- 9003926
TI  - Tolerability and utility of mangafodipir trisodium injection (MnDPDP) at the dose
      of 5 mumol/kg body weight in detecting focal liver tumors: results of a phase III
      trial using an infusion technique.
AB  - PURPOSE: To evaluate the tolerability of mangafodipir trisodium (MnDPDP) and its
      utility for enhancing the ability of magnetic resonance (MR) imaging to detect
      focal hepatic lesions compared with non-enhanced MR and contrast-enhanced
      computed tomography (CT). MATERIALS AND METHODS: 119 patients with focal hepatic
      lesions were examined by MR and by contrast-enhanced CT. MR was performed before
      and after the infusion of 5 mumol/kg MnDPDP, at a concentration of 10 mumol/ml.
      Histologic confirmation was obtained in 79 patients. RESULTS: There were no
      severe adverse events. Five patients reported mild adverse events related to the
      infusion. MnDPDP-enhanced SE T1 and GE T1 sequences revealed more focal lesions
      than the same sequences before contrast infusion in, respectively 22.6 and 36.1%
      of the cases, and fewer focal lesions in, respectively 5.9 and 1.7% of the cases.
      Contrast-enhanced MR demonstrated more focal lesions than the SE T2 sequence in
      29.4% of cases and fewer lesions in 5.9% of cases. MnDPDP-enhanced MR revealed
      more nodules than CT in 31.1% of cases and fewer nodules in 13.4% of cases. The
      additional information provided by MnDPDP enhancement led to modification of
      management for 12 patients (10.1%). CONCLUSION: MnDPDP is a well-tolerated
      contrast agent allowing better MR detection of focal hepatic lesions than non
      enhanced MR or contrast-enhanced CT.

PMID- 9003927
TI  - Diagnostic potential of pseudo-dynamic MRI (CINE mode) for evaluation of internal
      derangement of the TMJ.
AB  - In addition to the patient's history and a thorough clinical investigation,
      magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ) has been
      introduced to complete the findings for the diagnosis of internal derangement of
      the TMJ. However, 'dynamic information' is desirable to help us to understand the
      mechanism of internal derangement. This information is given for example by
      electronic axiography recording systems. The lack of any ability to assess joint
      function dynamically in MRI is a point of criticism. Using a computer-driven
      pseudodynamic MRI system (CINE mode) 'dynamic information' should be now
      available. In this investigation 21 patients with TMJ disorders were examined
      using both conventional static MRI and CINE mode. For the diagnosis of an
      anterior displaced disc with or without reduction in 18 cases (86%) it was only
      necessary to consider two static MRIs: a closed mouth position and a maximal open
      mouth position. Comparison showed there was no advantage in using CINE mode.
      Contrast and resolution of the static MRIs were shown to be better and so
      additional findings such as joint effusion and disc deformation could be
      diagnosed on static MRIs with greater certainty. Only in three (14%) cases was
      the dynamic information from CINE mode useful for the diagnosis of the
      displacement of the disc.

PMID- 9003928
TI  - Measurement of tendon excursion velocity with colour Doppler imaging: a
      preliminary study on flexor pollicis longus muscle.
AB  - PURPOSE: To study the use of colour Doppler imaging (CDI) for the measurement of
      maximum and mean tendon velocity. Recent studies showed that CDI, normally used
      for blood flow examinations, can be used for the imaging of tendons at the hand
      and wrist region. Although other modalities are available for imaging of the
      muscle-skeletal system, in vivo measurements of the velocity of tendon excursion
      are not possible. METHODS: The flexor pollicis longus (FPL) tendon of 16 healthy
      volunteers was measured bilaterally at two levels (wrist and thenar). A splint
      from the fingers along the proximal lower arm was applied. The thumb was fixed to
      the splint from the the first phalanx to allow flexion of the interphalangeal
      (IP) joint only. Pulsed CDI was used for the measurements. The maximum and mean
      velocities of the FPL tendon were measured at spectrum display mode during
      continuous voluntary contractions. At least 10 sequential Doppler peaks (cm/s)
      were recorded at every trial. The measurements were repeated three times. Paired
      t-test and correlation coefficients were calculated between levels on the same
      side and the opposite side. RESULTS: No significant differences were found
      between two levels of the same hand and of the opposite hand. As expected, the
      data revealed variations in the inter-individual tendon velocities. CONCLUSIONS:
      The velocity of the excursion of the FPL tendon can be measured with CDI with
      good reproducibility. It is expected that velocity measurements can be used in
      the future for the assessment of other tendons affected by various disorders.

PMID- 9003929
TI  - Magnetic resonance imaging in the measurement of clinical stage IB cervical
      carcinoma.
AB  - MRI can accurately define the extension of cervical carcinoma to the parametria.
      However, in patients with cervical carcinoma clinical stage IB, the definition of
      the dimensions of the tumour, prior to surgery, and may also modify the treatment
      procedure. Recently pre-operative neoadjuvant chemotherapy has been proposed for
      patients with bulky tumours. Multiple factors may influence the prognosis of
      clinical stage IB and survival varies greatly among these patients. In particular
      the maximum dimensions of the tumour seem to have a prognostic relevance. The aim
      of this paper is to evaluate the potential of MRI to measure tumour size, in
      order to discriminate between patients needing surgery alone or pre-operative
      therapy followed by surgery. In 20 patients with clinical stage IB cervical
      carcinoma we performed MRI to measure the radius of the cervix, the radius of the
      tumour and their ratios. The measurements obtained have been compared with the
      corresponding data from histopathology of the operative specimens. The close
      correspondence between these linear measurements allows us to propose MRI as a
      reliable method to define tumour size in clinical stage IB patients before
      surgery.

PMID- 9003930
TI  - CT and MRI findings after stereotactic resection of brain lesions.
AB  - OBJECTIVE: To describe postoperative CT and MRI findings and their time course in
      uncomplicated cases after stereotactic volumetric resections of brain lesions.
      MATERIALS AND METHODS: One-hundred twenty-eight imaging studies (CT, 86; MRI,
      42), performed 6 h to 2 years after 52 stereotactic operations, were
      retrospectively reviewed and analyzed in relation to time of surgery in cases
      without complications. RESULTS: The extent of resection bed did not change during
      the first week after operation; reduction of size then began and continued up to
      3-6 months. Mass effect and edema showed no changed during the first 4 days, then
      later regressed gradually. Pneumocephalus was found in 58% of cases in the first
      3 weeks, but never later. Benign, surgically-induced enhancement appeared at the
      margins of encephalotomy and retractor at the end of the first postoperative
      week, became more prominent during the following weeks, and lasted up to 3-5
      months. In the majority of cases enhancement prevented recognition of the
      residual tumor. Dural enhancement was observed at the craniotomy site very early
      after the operation and persisted up to 1 year. Meningeal enhancement over
      convexities was found in 44% of MRI studies. CONCLUSION: Extent of the resection
      bed, mass effect, edema, and pneumocephalus show, in uncomplicated cases, a
      regular regression during the postoperative period. The time course of
      enhancement is complex and can be a source of diagnostic misinterpretation.

PMID- 9003931
TI  - The value of pre-operative ultrasound mapping of the greater saphenous vein prior
      to 'closed' in situ bypass operations.
AB  - OBJECTIVE: The aim of this study was to test pre-operative ultrasound mapping for
      the detection of duplications and narrow vein segments of the greater saphenous
      vein (GSV) used as bypass for occlusive arterial disease surgery. PATIENTS AND
      METHODS: In 44 patients pre-operative ultrasound findings of duplications and
      lumen assessment of GSV were compared to the per-operative findings. RESULTS: In
      nine patients (20%) the pre-operative ultrasound examination showed a
      duplication. Pre-operative ultrasound had missed a duplication in two cases but
      had instead shown a narrow segment in both. The pre-operative ultrasound
      assessment of lumen diameter showed a narrow lumen segment in 10 of the 44
      patients. In one patient a per-operatively narrow lumen had not been seen on pre
      operative ultrasound. CONCLUSION: Pre-operative ultrasound mapping of the GSV is
      a sensitive tool for detection of duplications and narrow vein segments. Since
      these anatomical variations provide important information for the vascular
      surgeon, before performing a 'closed' in situ bypass operation, pre-operative
      vein mapping should be considered when planning such a procedure.

PMID- 9003933
TI  - CT diagnosis of granulomatous mediastinitis due to tuberculosis.

PMID- 9003934
TI  - Traumatic bowing of the forearm in a child.

PMID- 9003932
TI  - Imaging in acute renal colic: the intravenous urogram remains the gold standard.
AB  - In a prospective study of 150 consecutive patients presenting over a 1-year
      period with acute renal colic, we compared the accuracy of intravenous urogram
      (i.v.u.) and ultrasound (US) in identifying and localizing ureteric calculi and
      hydronephrosis. i.v.u. was far superior to US. It identified 141 ureteric calculi
      vs. only one by US (P < 0.00001) and 109 hydronephroses vs. 66 (P < 0.0001). It
      is concluded that i.v.u. remains the gold standard for imaging in acute renal
      colic. US +/- plain supine abdominal film should be reserved for contrast medium
      risk patients and those in whom radiation is relatively contraindicated.

PMID- 9003935
TI  - Tension pericardial collections: sign of 'flattened heart' in CT.

PMID- 9003936
TI  - A social contract for 21st century health care: three-tier health care with
      bounty hunting.

PMID- 9003937
TI  - Nonsampling measurement error in administrative data: implications for economic
      evaluations.
AB  - Administrative databases are increasingly being used to measure resource use in
      economic evaluations. Traditionally, it is assumed that any measurement error
      within the resource data source is stochastic and uncorrelated with group
      assignment. If the error is correlated with characteristics of the service
      delivery system and/or correlated by group, the estimated differences in
      consumption between groups may be reflecting errors in measurement rather than
      treatment effects. This paper is concerned with the effect of nonsampling
      measurement error on the internal and external validity of cost estimates based
      on data drawn from administrative record systems. Two service delivery
      characteristics, ownership form and financial incentives, are likely to influence
      systemically an agency's data collection effort. Using data from three community
      mental health centres located in three different states, evidence of systematic
      differences in data quality was found; private agencies with reimbursement
      property rights had higher quality data than public agencies without property
      rights. Simple tests for detecting variation in service use and costs data and
      cost-effective solutions for managing these problems are proposed.

PMID- 9003938
TI  - An economic approach to clinical trial design and research priority-setting.
AB  - Whilst significant advances have been made in persuading clinical researchers of
      the value of conducting economic evaluation alongside clinical trials, a number
      of problems remain. The most fundamental is the fact that economic principles are
      almost entirely ignored in the traditional approach to trial design. For example,
      in the selection of an optimal sample size no consideration is given to the
      marginal costs or benefits of sample information. In the traditional approach
      this can lead to either unbounded or arbitrary sample sizes. This paper presents
      a decision-analytic approach to trial design which takes explicit account of the
      costs of sampling, the benefits of sample information and the decision rules of
      cost-effectiveness analysis. It also provides a consistent framework for setting
      priorities in research funding and establishes a set of screens (or hurdles) to
      evaluate the potential cost-effectiveness of research proposals. The framework
      permits research priority setting based explicitly on the budget constraint faced
      by clinical practitioners and on the information available prior to prospective
      research. It demonstrates the link between the value of clinical research and the
      budgetary restrictions on service provision, and it provides practical tools to
      establish the optimal allocation of resources between areas of clinical research
      or between service provision and research.

PMID- 9003939
TI  - Biases in cost measurement for economic evaluation studies in health care.
AB  - This paper addresses the issue of biases in cost measures which used in economic
      evaluation studies. The basic measure of hospital costs which is used by most
      investigators is unit cost. Focusing on this measure, a set of criteria which the
      basic measures must fulfil in order to approximate the marginal cost (MC) of a
      service for the relevant product, in the representative site, was identified.
      Then four distinct biases--a scale bias, a case mix bias, a methods bias and a
      site selection bias--each of which reflects the divergence of the unit cost
      measure from the desired MC measure, were identified. Measures are proposed for
      several of these biases and it is suggested how they can be corrected.

PMID- 9003940
TI  - Valuation of health changes with the contingent valuation method: a test of scope
      and question order effects.
AB  - In recent years, there has been a growing interest in the contingent valuation
      method for measurement of monetary values of various commodities. However, the
      validity and reliability of the method need to be examined thoroughly. This paper
      reports results of a test of scope and question order effects in a contingent
      valuation experiment in the health care field. Using three binary valuation
      questions, data were collected on willingness to pay for superior treatment of
      reflux oesophagitis. To test for scope effects, different probabilities of
      successful short- and long-term treatments were evaluated using a split sample
      approach. The presence of question order effects was tested by assigning
      respondents to different question orders. The contingent valuation method proved
      sensitive to changes in scope in that the willingness to pay increased with the
      probability of being free from symptoms and with a reduced risk of having a
      relapse once recovered. Also, regression analysis indicate that people who suffer
      from severe reflux oesophagitis are more willing to pay for more effective
      treatment. No question order effects were detected in the data.

PMID- 9003941
TI  - Using willingness to pay to assess the benefits of assisted reproductive
      techniques.
AB  - Current economic evaluations of Assisted Reproductive Techniques (ARTs) are
      criticized for assuming that the only factor important to users is whether they
      leave the service with a child. Such an approach ignores, first, outcomes beyond
      some narrow medical definition of success, second, the majority of users who
      leave the service childless and, third, the actual process of treatment. The aim
      of this study was to establish the importance of factors beyond some medical
      definition of success in the provision of ARTs, using the economic instrument of
      willingness to pay (WTP). The results suggest that there is some value in going
      through the service, even if the couple leaves it childless. It is concluded that
      the WTP technique is potentially useful in evaluating ARTs but further studies
      need to be undertaken to assess its reliability and validity.

PMID- 9003942
TI  - Where to be born? A normative approach of life duration inequalities in the
      world.
AB  - The following study attempts to demonstrate that traditional classifications of
      OECD countries according to the health condition of their citizens, based on
      classifications of life expectancy and infant mortality, can lead to substantial
      normative errors if we assume that economic agents are rational. In particular,
      classifications of life expectancy and infant mortality can cause a great deal of
      information loss, and do not allow a precise idea of typical inequalities in
      certain countries. This study begins with Meyer's method of classification--which
      allows us to organise different distributions on the basis of risk aversion of
      agents. This means that countries can be classified as offering a distribution
      superior to others in regards to the life duration they offer their citizens.

PMID- 9003943
TI  - The relationship between health expenditures and the age structure of the
      population in OECD countries.
AB  - The purpose of this study was to analyse national health expenditures of OECD
      countries relative to their age structures. Using econometric techniques designed
      to analyse cross-sectional time series data, the ageing of the population was
      found to affect health spending in several countries while having no effect in
      others. In addition, the effect of income on health spending was lower than that
      generally reported in the literature. These findings suggest that unobserved
      country-specific factors play a major role in determining the amount of resources
      allocated to health services in a country. Such factors also determine if the
      ageing of the population with increased health spending.

PMID- 9003945
TI  - Influence of compression of the inferior vena cava in the late second trimester
      on uterine and umbilical artery blood flow.
AB  - OBJECTIVE: To evaluate the inferior vena cava compression and its influence on
      the uterine and umbilical artery blood flow in the late second trimester when the
      mother is supine. METHODS: The inferior vena cava diameter was measured by
      ultrasound B mode scan, and Doppler flow velocimetry of the uterine and umbilical
      artery was performed in 90 women at 24-27 weeks in the supine and complete left
      lateral position. RESULTS: The inferior vena cava diameter in the supine position
      was significantly smaller than that in the lateral position. The degree of the
      vena cava compression was associated with an elevation in the uterine artery RI
      in the supine position. The umbilical artery RI did not couple with either the
      degree of the compression or the changes in the uterine artery RI. CONCLUSION:
      The inferior vena cava is compressed in the majority of pregnant women in the
      second trimester, and the compression may affect the uterine artery blood flow
      but not the fetal circulation.

PMID- 9003944
TI  - Evaluation of chemical tests for fetal bleeding from vasa previa.
AB  - OBJECTIVES: To evaluate different alkaline denaturation tests and compare with
      hemoglobin electrophoresis and the Kleihauer test, and to identify the simplest
      and most sensitive test that may help to rapidly show the presence of fetal
      hemoglobin and establish the diagnosis of fetal bleeding from vasa previa.
      METHODS: Maternal and fetal cord blood were obtained from 20 women with
      uncomplicated deliveries and the samples were mixed in known concentrations
      ranging from 0-100% fetal blood. Further samples were prepared in which maternal
      and fetal blood mixtures were diluted with amniotic fluid so that the final
      concentration of fetal hemoglobin similarly ranged from 0-100%. Alkaline
      denaturation tests (Apt, Ogita, Loendersloot), hemoglobin electrophoresis and
      Kleihauer tests were performed on all 40 samples. RESULTS: The Apt and
      Loendersloot tests were clearly positive at 60% concentrations of fetal blood. It
      took approximately 7 and 4 min, respectively, to complete the tests. The Ogita
      test was positive from fetal blood concentrations of 20% and took approximately 5
      min. Hemoglobin electrophoresis took approximately 1 h to complete and the Hb-F
      band was present even at 0% concentration of fetal blood and the band became more
      marked with increasing fetal blood concentration. The Kleihauer test was negative
      at 0% but positive from 0.01% fetal blood concentration. The test took
      approximately 45 min to perform. CONCLUSIONS: The Ogita test is the best all
      round alkaline denaturation test that may help to rapidly identify the presence
      of fetal hemoglobin and so establish the need to expedite delivery when there is
      fetal bleeding from vasa previa. It is simple to perform, does not require
      sophisticated equipment, unlikely to give false positive results, and takes only
      5 min. The simplicity of the test makes it attractive for routine use on the
      labor ward.

PMID- 9003947
TI  - Obstetric outcome in uncomplicated prolonged pregnancy.
AB  - OBJECTIVE: To study and compare the obstetric outcome in term pregnancies and
      uncomplicated prolonged pregnancies. METHODS: The study was a retrospective
      review of 596 cases. The case notes of 286 patients with uncomplicated prolonged
      pregnancies (> or = 42 weeks) and 310 patients with normal term pregnancies (37
      to < 42 weeks) were analyzed. The Gold Stat package was used for statistical
      coding and analysis. RESULTS: There was no fetal morbidity or mortality among the
      two groups. However, the number of previous abortions were significantly higher
      in prolonged pregnancies compared with term pregnancies. Similarly, fetal and
      placental weights, labor induction and operative delivery rates were
      significantly higher in prolonged pregnancies. However, there were no significant
      differences between the patients who were induced and those who had spontaneous
      labor among the prolonged pregnancies. CONCLUSIONS: There is no doubt that
      prolonged pregnancy may be associated with certain risks factors. However, there
      is no outcome variable to justify whether or not to induce those pregnancies
      which are prolonged.

PMID- 9003946
TI  - Perinatal outcome and the type and number of maneuvers in shoulder dystocia.
AB  - OBJECTIVES: To ascertain the type and order of maneuvers that should be used for
      the treatment of shoulder dystocia, and to determine its correlation with
      perinatal outcome. METHODS: We reviewed all consecutive cases of shoulder
      dystocia from January 1986 to August 1994 in our institution to obtain the type,
      order and number of maneuvers used for delivery. Patients were stratified by the
      number of maneuvers required for delivery. Outcome parameters included cord pH,
      Apgar score, neonatal trauma (Erb's palsy and fracture), and maternal trauma.
      RESULTS: The incidence of shoulder dystocia was 0.7% (39,280 total vaginal
      deliveries). Use of only two maneuvers, McRoberts and suprapubic pressure,
      resulted in resolution in 58% of cases. The addition of the Woods screw maneuver
      and/or delivery of the posterior arm was sufficient in all remaining cases. The
      rates of neonatal palsy and fracture, and maternal four-degree laceration,
      increased with the number of maneuvers. CONCLUSIONS: The McRoberts maneuver and
      suprapubic pressure should be first-line treatment for shoulder dystocia. More
      difficult and damaging maneuvers such as Woods screw and delivery of the
      posterior arm may be reserved for refractory cases. Additional maneuvers are
      rarely necessary for delivery. The number of maneuvers may serve as a measure of
      the severity of the shoulder dystocia.

PMID- 9003948
TI  - Maternal and fetal outcomes in hyperemesis gravidarum.
AB  - OBJECTIVE: This study sought to evaluate maternal characteristics and pregnancy
      outcomes among women with hyperemesis gravidarum. METHODS: We performed a
      retrospective analysis of pregnancy records of obstetric admissions during a 6
      year period. Women treated as out-patients for hyperemesis were also identified.
      Hyperemesis was defined as excessive nausea and vomiting resulting in
      dehydration, extensive medical therapy, and/or hospital admission. Statistical
      analysis was by t-test and chi square. RESULTS: We identified 193 women (1.5%)
      who developed hyperemesis among 13,053 women. Racial status, marital status, age,
      and gravidity were similar between the hyperemesis patients and the general
      population. However, there were less women with hyperemesis who were para 3 or
      greater. Forty-six women (24%) required hospitalization for hyperemesis, mean
      hospital stay 1.8 days, range 1-10 days. One patient required parenteral
      nutrition, two had yeast esophagitis, none had HIV infection, psychiatric
      pathology or thyroid disease. Pregnancy outcomes between hyperemesis patients and
      the general population were similar for mean birth weight, mean gestational age,
      deliveries less than 37 weeks, Apgar scores, perinatal mortality or incidence of
      fetal anomalies. Our incidence of hyperemesis (1.5%) is similar to that of other
      published reports. CONCLUSION: Women with hyperemesis have similar demographic
      characteristics to the general obstetric population, and have similar obstetric
      outcomes.

PMID- 9003949
TI  - Laser miniconization procedure.
AB  - OBJECTIVE: To describe the outpatient procedure of minimal conization with free
      hand guided high power density carbon dioxide laser for simultaneous diagnosis
      and treatment of CIN producing a one-piece tissue specimen for histological
      examination. MATERIAL AND METHODS: 3100 non-pregnant patients with mild, moderate
      or severe dysplasia in pap smear, having colposcopically proved ectocervical
      lesions but without evidence of invasive carcinoma, or 85 pregnant patients with
      severe dysplasia in pap smear having extensive colposcopic signs of at least
      carcinoma in situ were admitted for this treatment. This outpatient procedure
      including cervical curettage is performed under local anesthesia to excise a one
      piece 5 mm (during pregnancy 7 mm) deep minicone. RESULTS: The degree of patient
      discomfort, bleeding complications, postoperative pain, infection or vaginal
      discharge were all minimal. The procedure was fast, causing minimal thermal
      damage of resection lines of the minicone specimen. Histopathological examination
      of the non-pregnant minicones revealed microinvasive or invasive carcinoma in
      1.2%, the primary cure rate was 96.1%. During pregnancy, 13.3% malignancy was
      found. No unexpected sudden onset of invasive carcinoma was recorded during the
      15-year follow-up and the cumulative risk of recurrence for all forms of CIN was
      3.02% CONCLUSIONS: The outpatient miniconization procedure, performed with a free
      hand guided 60-W high power density CO2 laser is a reliable method for
      simultaneous diagnosis and treatment of CIN. Because of the paucity of
      complications, this procedure may also be appropriate during pregnancy.

PMID- 9003950
TI  - Laparoscopic total abdominal hysterectomy by suturing technique, with no
      transvaginal surgical approach: a review of 276 cases.
AB  - OBJECTIVE: To determine the effectiveness and safety of the new technique of
      laparoscopic total abdominal hysterectomy with prophylactic retroperitoneal
      rectovaginal-pouch of Douglas reconstruction and vaginal vault re-suspension by
      suturing method, with no transvaginal surgical approach. METHODS: The clinical
      prospective study included 276 women, and was conducted from July 1990 through
      December 1995. All women were subjected to a laparoscopic total abdominal
      hysterectomy with prophylactic retroperitoneal rectovaginal and pouch of Douglas
      reconstruction and vaginal vault suspension. The entire operation was executed
      via laparoscope with suturing and tying of extracorporeal sliding and
      intracorporeal two-turn flat square knot technique, and no transvaginal surgery
      was performed. The criteria for postoperative early (within 5 h) discharge plan
      were designed and assessed. RESULTS: All pre-planned instances of laparoscopic
      total abdominal hysterectomy with prophylactic retroperitoneal rectovaginal-pouch
      of Douglas reconstruction and vaginal vault re-suspension were completed; no
      technique failure was encountered. The average operating time for both
      hysterectomy and prophylactic surgery was 192 min. Intraoperative complications
      were two bladder injuries (0.72%); one case of inferior epigastric vessels injury
      (0.36%); one case of autologous, cells saver processed blood transfusion (0.36%).
      The immediate postoperative complications were four cases of voiding difficulty
      (1.45%) and five patients experiencing post anesthesia inordinate nausea and
      vomiting (1.81%). One patient required postoperative blood transfusion (0.36%).
      Delayed postoperative complications included 2 patients (0.72%) with superficial
      incisional skin infection. Estimated hemoglobin loss was from 0.5 g/dl to 5.0
      g/dl, mean loss 1.5 g/dl. The extirpated uterine average weight 163 g.
      Postoperatively, within 24 h, 265 patients (96.01%) out of 276 were discharged
      home on the day of surgery, within 5 h, 110 patients (41.51%) out of 265 left the
      surgical unit. There was no single hospital post surgical re-admission.
      CONCLUSIONS: Laparoscopic total abdominal hysterectomy with prophylactic
      retroperitoneal rectovaginal-pouch of Douglas reconstruction and vaginal vault
      suspension by suturing method is a safe, well-defined operation, executed with no
      need for transvaginal surgical approach, and well accepted by patients.

PMID- 9003952
TI  - Erythropoietin, granulocyte-colony stimulating factor, interleukin-1 beta and
      interleukin-6 during the normal menstrual cycle.
AB  - OBJECTIVE: Menstruation and ovulation are the main events during the menstrual
      cycle. Menstruation may influence the complete blood count because of its blood
      loss. Since ovulation is an inflammatory-like phenomenon, white blood cell count
      may change during ovulation. For these reasons, we have investigated the complete
      blood count and peripheral serum concentrations of associated cytokines during
      the normal menstrual cycle. MATERIALS AND METHODS: Normal healthy female
      volunteers (N = 9; age, 21-33 years) with menstrual cycles of 25-33 days recorded
      basal body temperature every day and venous blood samples were collected three
      times per week. Complete blood count was performed and erythropoietin,
      granulocyte-colony, stimulating factor, interleukin-1 beta, interleukin-1 beta,
      interleukin-6 and hormones (FSH, LH, estradiol and progesterone) were measured.
      RESULTS: The red blood cell, total white blood cell, granulocyte and platelet
      counts showed no statistically significant changes during the menstrual cycle
      when using analysis of variance with the Scheffe F-test. No changes in
      erythropoietin, interleukin-1 beta and interleukin-6 were seen throughout the
      menstrual cycle. In contrast, serum granulocyte-colony stimulating factor
      concentrations increased significantly to 28.0 +/- 3.1 pg/ml (mean +/- S.E.M.)
      during the ovulatory phase, compared to 10.7 +/- 0.6 pg/ml in other phases.
      CONCLUSION: These results indicate that menstrual blood loss does not affect the
      complete blood count and suggest that granulocyte-colony stimulating factor plays
      and important role in the mechanism of ovulation.

PMID- 9003951
TI  - Topical oxatomide: an alternative approach for the treatment of vulvar lichen
      sclerosus.
AB  - OBJECTIVE: The treatment of vulvar lichen sclerosus has greatly improved in
      recent years, with the introduction of new pharmacological approaches and
      reconsideration of the traditional ones. Oxatomide is a molecule with both
      antihistamine and inhibiting activities for the inflammatory response, which may
      have potential use against this disease. METHODS: We enrolled 22 patients
      affected by vulvar lichen sclerosus in a double-blind, cross-over, controlled
      trial. They were administered a 5% oxatomide-based gel formulation and a placebo
      (petrolatum ointment) topically. At the beginning and the end of the
      investigation the severity and duration of symptoms, clinical appearance and
      tolerability were recorded. Statistical analysis of data was performed by
      Fisher's exact test and the Student-Newman-Keuls test. RESULTS: The results
      indicate that both regimens are significantly correlated with vulvar pruritus
      improvement and that 5% oxatomide gel has better anti-itching effects compared to
      the placebo. Other symptoms responded poorly to the treatment. The rate of
      complete-partial regression of pruritus was significantly higher (P < 0.05) in
      the oxatomide group than in controls, while no significant improvement was
      obtained neither with oxatomide or with placebo in terms of clinical appearance.
      CONCLUSIONS: These results, adequately confirmed, could suggest the introduction
      of oxatomide, in selected patients, as an alternative for the treatment of vulvar
      lichen sclerosus.

PMID- 9003954
TI  - Acute reversal of oligohydramnios-polyhydramnios sequence in monochorionic twins.
AB  - Two cases of monochorionic diamniotic twin gestation with severe oligohydramnios
      polyhydramnios sequence ('stuck' twin) are described. In each of these cases
      there was a marked fluctuation in amniotic fluid volume and reversal of which
      twin was 'stuck'. The definitive identification of the twins was evident due to a
      discordant fetal malformations in each twin pair.

PMID- 9003953
TI  - Serum alpha L-fucosidase enzyme activity in ovarian and other female genital
      tract tumors.
AB  - OBJECTIVES: To assess the value of serum alpha-L-fucosidase as a tumor marker in
      the diagnosis of ovarian and other female genital tract tumors. METHODS: One
      hundred fifty-one patients were studied; 101 had different genital tract tumors
      (malignant ovarian tumors (48), carcinoma of the cervix (13), endometrial
      carcinoma (6), carcinoma of the vulva (6) and benign tumors (28)). A control
      group of 50 healthy female patients was included. Serum alpha-L-fucosidase
      activity was determined in all patients and controls. Serum CA 125 level was also
      determined in patients with malignant ovarian tumors. RESULTS: patients with
      malignant ovarian tumors showed the lowest level of alpha-L-fucosidase activity
      in comparison to other malignant and benign tumors of the female genital tract
      and also in comparison to malignant ovarian tumors. RESULTS: Patients with
      malignant ovarian tumors showed the lowest level of alpha-L-fucosidase activity
      in comparison to other malignant and benign tumors of the female genital tract
      and also in comparison to control group. The majority of ovarian carcinoma
      patients (90%) had a serum level of < 275 u/ml of alpha-L-fucosidase activity,
      while more than 90% of the control group and other genital tumors had a serum
      level of > 275 u/ml. The sensitivity and specificity of serum alpha-L-fucosidase
      activity in diagnosing epithelial ovarian tumors were 88.5% and 98%, respectively
      (using a cut-off level of < 275 u/ml). The corresponding figures for CA 125 were
      96.2% and 100% (using a cut-off level of > 35 u/ml). CONCLUSIONS: Serum alpha-L
      fucosidase enzyme activity can be useful as a tumor marker in diagnosing advanced
      malignant epithelial ovarian tumors. Its sensitivity and specificity are
      comparable to CA 125. However, there is a lack of data to support its usefulness
      in the diagnosis of early stage disease (Stage 1). The cost of doing the test is
      one-third that of CA 125 and the test can be more widely applied in developing
      countries.

PMID- 9003955
TI  - The practice of female genital mutilation in upper Egypt.
AB  - OBJECTIVE: To study the prevalence of and reasons for female genital mutilation
      in an Egyptian village population. METHODS: A survey of all 819 households in an
      Upper Egyptian village near Assiut was conducted in 1992. The mothers of 1,732
      girls under 20 years of age were interviewed to obtain information about their
      daughters. When possible, fathers and grandparents were also interviewed.
      RESULTS: Respectively, 62%, 36.6% and 1.1% were girls who had undergone female
      genital mutilation (FGM), were to undergo the procedure and were not to have the
      operation. A total of 67% of the fathers of girls who had undergone FGM and 92%
      of their mothers were illiterate. FGM was performed most often when girls were 5
      9 years old. Almost all procedures (97.5%) were performed by dayas; 1.3% were
      performed by barbers. A razor was used in 80.7% of the cases, and a knife in
      18.5%; in less than 1% (0.7%) of the procedures were medical instruments used.
      The most prevalent reason for FGM was that it followed customs and traditions
      (77%). Serious bleeding (5.7%) and pain (3%) were the most commonly reported
      complications of the procedure. CONCLUSIONS: The study raises a number of
      questions about the experience of FGM by young girls, the reasons for maintaining
      this practice and the kinds of interventions which might be effective in
      eliminating it.

PMID- 9003956
TI  - Post tonsillitic erythema nodosum in pregnancy.

PMID- 9003957
TI  - The predictive value of adjunctive NST and AST in high-risk pregnancies.

PMID- 9003958
TI  - Gaseous distention of the urinary bag indicating bladder perforation during
      laparoscopic pelvic procedures.

PMID- 9003960
TI  - ACOG committee opinion. Scope of services for uncomplicated obstetric care.
      Number 175, September 1996 (replaces no. 79, January 1990). American College of
      Obstetricians and Gynecologists.

PMID- 9003959
TI  - ACOG educational bulletin. Maternal serum screening. Number 228, September 1996
      (replaces no. 154, April 1991). Committee on Educational Bulletins of the
      American College of Obstetricians and Gynecologists.
AB  - Maternal serum screening offers women the ability to increase the detection of
      open fetal defects, Down syndrome, and trisomy 18. After being informed of the
      risks and advantages of serum screening, a patient may elect to be screened.
      Counseling must emphasize that serum screening for these disorders is voluntary,
      and patients must be aware that further evaluation, if their results are
      classified as positive, may include amniocentesis. Physicians should have access
      to genetic services and reliable laboratories to assist them in the management of
      maternal serum screening and genetic procedures. Special attention must be given
      to the older gravida to help her make an appropriate personal decision regarding
      screening and genetic testing. Patients receiving positive results from a
      definitive test (karyotype or, possibly, ultrasonography) should have access to
      adequate counseling, including the availability of support groups and pediatric
      surgeons.

PMID- 9003961
TI  - Favorable effect of transcranial electrostimulation on behavior disorders in
      elderly patients with dementia: a double-blind study.
AB  - The efficacy of transcranial electrostimulation for sleep-wake and behavior
      disorders in elderly patients with dementia was tested in a double-blind study.
      The subjects were 27 inpatients with multi-infarct dementia (12 males and 15
      females, aged 58-86). They were randomly divided into two groups: active
      treatment (n = 14) and placebo treatment (n = 13). For electrostimulation, a
      device (HESS-100) was used which delivered repetitive rectangular electric pulses
      of 6-8 V at increasing frequencies from 6 to 80 Hz, each pulse lasting 0.2 ms and
      with a root mean square value of 256-530 microA. Electrostimulation was performed
      for 20 minutes from 10:00 h every morning. The active or placebo treatment was
      performed for 2 weeks in each group. The electrostimulation was significantly
      effective in behavior disorders such as wandering or nocturnal delirium, and
      decreased motivation during the daytime. It was also effective in improving night
      sleep. Electroencephalograms confirmed increased vigilance levels in the daytime
      both during and after the treatment.

PMID- 9003962
TI  - Two statistical methods for analyzing multiple neuronal data.
AB  - We applied two methods based on statistical analysis to neuronal data of multiple
      neurons. One is based on ANOVA (analysis of variance) and the other PCA
      (principal component analysis). These methods describe neuronal responses of
      multiple neurons from two different view-points; the former is that neuronal
      encoding is performed by cell by cell basis whereas the latter is that neuronal
      encoding is performed by a population of neurons. Applying these methods to data
      from single-unit recording experiments, we demonstrate that the former method
      enables us to determine whether a population of neurons significantly responds to
      a set of stimuli whereas the latter method can be used to determine whether
      collective neuronal responses have significant structure along the time axis.

PMID- 9003963
TI  - Sociodemography of borderline personality disorder (PD): a comparison with Axis
      II PDs and psychiatric symptom disorders convergent validation.
AB  - A theoretical objective of the present meta-analysis based upon data derived from
      a previously reported review (Taub, 1995), was to test two inductive hypotheses
      empirically regarding educational background and social class across different
      criteria for the DSM-III diagnosis of borderline personality disorder (PD). A
      secondary purpose was to determine whether comorbidity of borderline PD with
      other Axis II PDs would significantly delineate socioeducational variables.
      Across 7/8 pairwise contrasts which represented five studies, distribution of
      Hollingshead Redlich (H-R) social classes II-IV borderline PD (N = 326)
      significantly exceeded that in 457 diagnostic controls with Axis II PDs and
      psychiatric symptom disorders. Although average differences, as well as,
      interactions reflected by values of the H-R two-factor scale attained statistical
      significance these were were less consistent in magnitude and direction versus
      outcomes yielded by distribution of social classes. For the borderline PD
      diagnosis, the inductive hypotheses were substantiated by findings of
      significantly advanced scholastic achievement, as well as the younger age of most
      cohorts versus diagnostic controls with Axis II PDs and psychiatric symptom
      disorders; and in pairwise contrasts of outpatients with hospitalized cohorts.
      Comorbidity of the borderline PD diagnosis was associated with significantly
      lower social class, scholastic achievement and to a lesser extent, more severe
      psychopathology. Evidence for predominantly convergent validation relative to the
      socioeducational variables was substantiated by comparisons with (a) cohorts
      selected by criteria of the DSM-III-R, Gunderson's DIB and Borderline Personality
      Scale: (b) Norwegian females admitted to Gaustad Hospital and (c) patients with
      the DSM-III diagnosis of borderline PD attending an outpatient clinic in Norway.

PMID- 9003965
TI  - Treatment with weak electromagnetic fields controls drooling in Parkinson's
      disease.

PMID- 9003964
TI  - Does gamma-hydroxybutyrate inhibit or stimulate central DA release?
AB  - Gamma-hydroxybutyrate (GHB), a four-carbon fatty acid and anaesthetic, is widely
      considered to be a relatively specific inhibitor of central dopamine (DA)
      release. The inhibitory effect of GHB on the latter is thought to occur as a
      consequence of its diminution of impulse flow in central dopaminergic neurons.
      However, a number of studies have recently reported that GHB primarily stimulates
      rather than inhibits central DA release, with any inhibitory effect produced of a
      modest and transitory nature. GHB has been and continues to be widely used as an
      important research tool largely because it is one of only a few drugs available
      that acts primarily on DA release. Consequently, it is important to determine
      whether GHB inhibits DA release as previously thought, or stimulates DA release,
      as more recently suggested. Following a critical review of the literature, the
      present report suggests that GHB does inhibit rather than stimulate presynaptic
      DA release in consonance with its behavioral and pharmacological activity. Recent
      in vivo studies indicating that GHB stimulates DA release were done under
      anaesthesia or in the presence of a high concentration of calcium. Both
      conditions have been found to spuriously enhance striatal DA release in vivo,
      which may account for the failure of some studies to observe an inhibitory effect
      of GHB on DA release in vivo.

PMID- 9003966
TI  - Treatment with electromagnetic field alters the clinical course of chronic
      progressive multiple sclerosis--a case report.
AB  - It is estimated that 10-20% of patients with multiple sclerosis (MS) have a
      chronic progressive (CP) course characterized by an insidious of neurological
      deficits followed by steady progression of disability in the absence of
      symptomatic remission. No therapeutic modality has shown specific efficacy in the
      treatment of patients with CP MS and there are no data to indicate that any
      pharmacologic or other modality alters the clinical course of CP MS. Treatment
      with picotesla electromagnetic fields (EMFs) is a highly effective modality for
      the symptomatic management of MS including the chronic progressive form. In
      addition, this treatment also appears to alter the natural course of the disease
      in CP patients. A 36 year-old man experienced, at the age of 31, insidious
      weakness in the legs and several months later developed difficulties with balance
      with ataxia of gait. His gait abnormality progressed slowly over the following
      years and at the age of 35 he was severely disabled with spastic paraparesis and
      ataxia using a rolling walker for ambulation and a scooter for longer distances.
      In particular, his disability had progressed rapidly over the six months
      preceding the initiation of treatment with EMFs. He as classified have CP MS and
      his prognosis was considered extremely unfavorable due to the degree of
      cerebellar and pyramidal tract involvement and the rapid course of deterioration.
      In July 1995 the patient began experimental treatment with EMFs. While receiving
      three treatment sessions a week over 12 months he experienced improvement in
      cerebellar functions such as gait, balance and tremor as well as bowel and
      bladder functions, mood, sleep and cognitive function and resolution of diplopia,
      blurring of vision, dysarthria, paresthesias in the hands, and fatigue. Most
      remarkably, there was no further progression of the disease during the course of
      magnetic therapy. This case illustrated that treatment with EMFs, in addition to
      producing symptomatic improvement, also reverses the clinical course of CP MS.

PMID- 9003967
TI  - Sex-related engagement of the hemispheres in visuospatial processing.
AB  - Hemispheric asymmetries in visuospatial functions were investigated in women and
      men with a tachistoscopic task using lateralized presentation of "Necker" cubes.
      A lexical decision task served as control. In either of the two tasks the
      procedure involved a bilateral presentation of correct and distorted items and
      responses had to be given by means of a nonverbal decision task. The analysis of
      hits in the cube task showed a right visual field advantage for women and a left
      visual field advantage for men, but women had more false alarms in the right
      visual field, whereas men showed the reverse pattern again. The lexical decision
      task showed similar response patterns for men and women. The distinct response
      behavior supports the hypothesis that tasks allowing for various strategies to
      choose from obviously are better suited to elicit a differential engagement of
      the two hemispheres in women and men.

PMID- 9003968
TI  - Cognitive performances in newly referred patients with temporal lobe epilepsy:
      comparison with normal subjects in basal condition and after treatment with
      controlled-release carbamazepine.
AB  - In order to verify whether the performance of patients with temporal lobe
      epilepsy (TLE) were different from those of the normal controls in various
      cognitive tasks, we conducted a neuropsychological study in the two groups,
      excluding the presence of other confounding factors in the group of TLE patients
      (newly referred, previously untreated, without cerebral lesions at neuroimaging,
      with low recurrence of seizures). In basal condition, no significant difference
      was found between the nine healthy controls and the eight TLE patients. The
      second aim of the study was to investigate the effect of the first administration
      of 400 mg controlled-release carbamazepine (CBZ-CR). The drug caused a
      significant decrease in verbal memory (short and long-term) in TLE patients,
      whereas, in the control group, the first administration of CBZ-CR caused only a
      less significant impairment of long-term verbal-memory. Finally, the cognitive
      effects of CBZ-CR were assessed after one month of therapy, only in the group of
      patients. Our data suggest that: 1) differences between patients and controls in
      basal conditions are not relevant, once the influence of seizures, of treatment
      and of anatomical lesions has been ruled out. In other words, our patients did
      not perform differently from controls simply because they had become epileptic 2)
      also in the controlled-release preparation, adverse effects of CBZ on cognitive
      function are minimal and limited to the beginning of treatment.

PMID- 9003969
TI  - Visual event related potentials and reaction time in normal adults, normal
      children, and children with attention deficit hyperactivity disorder: differences
      in short-term memory processing.
AB  - Visual Event Related Potentials were recorded during a memory search paradigm in
      30 normal adults, 17 normal children, and 14 children with Attention Deficit
      Hyperactivity Disorder (ADHD). Group differences were found in P3 latency and
      amplitude, Reaction Time and number of errors. The findings indicate a different
      information processing pattern for ADHD children who possibly use a "self
      terminating" as opposed to "exhaustive" search strategy.

PMID- 9003970
TI  - Left and right hemispheric contributions to discourse coherence and cohesion.
AB  - Linguistic coherence and cohesion were examined in patients with unilateral left
      brain damage (LBD), unilateral right brain damage (RBD), and normal control (NC)
      right-handed adults. Groups were matched for age, gender, occupation, and
      education. Brain-damaged groups did not differ for months post onset or
      intrahemispheric lesion site. Contrary to previous literature, results indicated
      that LBDs, all of whom were aphasic, demonstrated impairments in coherence but
      not cohesion, relative to NCs and RBDs. Surprisingly, among RBDs, overall
      coherence and cohesion were spared. When the relationship between measures of
      coherence and cohesion was examined, there were few significant correlations and
      no systematic patterns. Results support the notion that coherence and cohesion
      represent coexisting and independent linguistic systems. Further, the findings
      suggest that descriptions of discourse integrity need to account for the
      perspective of both the speaker and listener.

PMID- 9003971
TI  - Brief communication: bilateral footedness and task complexity.
AB  - The primary intent of this investigation was to determine if stabilizing
      complexity (postural control) influenced lower limb selection while performing a
      bilateral footedness task. Right- and left-footed subjects (as determined by a
      bilateral preference inventory) were asked to stand on one foot and tap a
      telegraph key with the opposite foot repeatedly. The bilateral task was conducted
      in two conditions of stabilizing complexity, with the intent to augment focus of
      attention between stabilizing and mobilizing limb: simple (lights on) and complex
      (limitation of visual cues). Results indicated that in both simple and complex
      conditions, 50% or more of subjects switched stabilizing limbs or showed no
      preference when comparing preference inventory behavior to experimental
      conditions, suggesting, in general, that foot preference may be in part dependent
      on the context of the task and not tied predominantly to biological theory.

PMID- 9003972
TI  - Abnormal brain stem auditory evoked potentials in a girl with the central
      alveolar hypoventilation syndrome.
AB  - Brainstem auditory evoked potentials were recorded in a 3-year-old girl with the
      central alveolar hypoventilation syndrome (Ondine's syndrome). Abnormal findings
      were seen at the level of the mid to upper brain stem (wave III), which was not
      reproducibly recordable on the left side. This electrophysiologic abnormality is
      consistent with a previous finding in a patient with sleep apnea.

PMID- 9003973
TI  - Posterior fossa lesions associated with neuropsychiatric symptomatology.
AB  - We reviewed 7 cases with posterior fossa structural abnormalities (3 tumors, 2
      megacisterna magna and 2 Dandy-Walker syndrome) presenting with neuropsychiatric
      symptomatology. Derangement in the balance of dopamine, serotonin and
      noradrenergic networks has been implicated in the pathogenesis of schizophrenia,
      affective and even personality disorders. Disruption of the cerebellar output to
      mesial dopaminergic areas, locus coeruleus and raphe nuclei, or deafferentation
      of the thalamolimbic circuits by a cerebellar lesion may lead to behavioral
      changes. Seven patients (pts) (comprising 4 men and 3 women with mean age 22
      years) were diagnosed as suffering from psychosis (2 pts), major depression (1
      pt), personality disorders (2 pts) and somatoform disorders (2 pts) (DSM-IV
      criteria). Brain CT scan (7 pts) and MRI (4 pts) revealed tumors of the posterior
      fossa (2 pts), megacisterna magna (2 pts) and Dandy-Walker variant (2 pts). In
      one patient a IVth ventricle tumor was removed in childhood.

PMID- 9003974
TI  - Daytime sleepiness and REM abnormalities in Prader-Willi syndrome: evidence of
      generalized hypoarousal.
AB  - The aim of this study was to clarify the nature of the sleep abnormalities
      (excessive daytime sleepiness [EDS] and rapid eye movement [REM] sleep
      alterations) in Prader-Willi; Syndrome (PWS). Eight PWS patients, 15 normal, 16
      narcoleptic, and 16 obese subjects were recorded in the sleep laboratory, both
      during daytime and nighttime. A principal-finding was that EDS in PWS was
      associated with an increased amount and depth of sleep. In PWS patients with EDS,
      compared to those PWS patients without EDS or the narcoleptic, obese, and normal
      groups, there were significant decreases in wakefulness and increases in
      percentage of sleep time (ST) and slow-wave sleep (SWS) both during daytime and
      nighttime testing. Also, in the adult PWS subjects (n = 6), in contrast to normal
      narcoleptic subjects, intensity of EDS was correlated with increased nocturnal
      percentage of ST and SWS and % SWS was positively correlated with % ST (both
      during daytime and nighttime testing). Another principal finding was that in PWS
      there is a unique alteration of the distribution of REM sleep in relation to
      controls. PWS patients with EDS or shortened nocturnal REM latencies showed a
      significantly increased number of REM periods, and a decreased average REM
      interval between REM periods compared to PWS patients with nonshortened nocturnal
      REM latencies or to the three control groups. Our data suggest that EDS and REM
      abnormalities in PWS are not manifestations of a narcoleptic-type syndrome or
      consequences of obesity. We propose that generalized 24-hour hypoarousal is the
      primary mechanism underlying the sleep abnormalities in PWS patients.

PMID- 9003975
TI  - Essential fatty acids preparation (SR-3) improves Alzheimer's patients quality of
      life.
AB  - In a number of previous reports we showed the salutary effects on rats of SR-3, a
      compound comprising a 1:4 ratio of n-3 and n-6 fatty acids. Improvements were
      noted in learning tasks, thermoregulation, recovery from neurotoxins, and seizure
      protection. Because we were impressed that these effects are related to changes
      in membrane fluidity and neuronal functioning and because Alzheimer's Disease is
      also associated with lipid defects, we undertook a short term (4 week) double
      blind study with 100 Alzheimer patients (60 received SR-3 and 40 in a placebo
      control). The results indicated improvements in mood, cooperation, appetite,
      sleep, ability to navigate in the home, and short term memory. Overall
      improvement was reported for 49 patients, and in no case did a guardian report
      adverse effects to the compound. While not uniform or permanent, and while no
      mode of action for SR-3 can be precisely identified at this time, the promising
      results in quality of life for the patient and caregiver warrant further clinical
      trials and continued basic research into the neuropsychological substrate of the
      disease and its response to SR-3.

PMID- 9003976
TI  - Event-related desynchronization (ERD) patterns to emotion-related feedback
      stimuli.
AB  - Event-related desynchronization (ERD) of alpha components was studied in 14
      healthy right handed subjects in an effective task. In the present study positive
      and negative emotions were operationalized by winning and losing certain amounts
      of money in a gambling situation while measuring ERD to positive and negative
      feedback stimuli. All the subjects demonstrated comparable (i.e. statistically
      not separated) intensities of positive and negative affect of self-report data.
      The obtained results suggest that ERD can be used as an indicator of localized
      brain activation in affective tasks. As it was evidenced by ERD analyses, the
      left and right lobes participated in Valence discrimination. The predicted
      relative left frontal activation to the positive feedback stimuli and right
      frontal activation to the negative feedback stimuli was supported. This effect
      was restricted to the upper (i.e. 10-12 Hz) alpha band. These findings are
      evidenced in favour of specific role of frontal hemispheric asymmetries in
      valence discrimination. It is concluded that ERD seems to be able to evidence
      relatively small differences in emotion processing and appears to be a suitable
      method with which to study emotion.

PMID- 9003977
TI  - Brief communication: effects of diagnostic irradiation during pregnancy on head
      circumference at birth.
AB  - A historical cohort study was carried out to evaluate the effects in utero
      medical ionizing radiation on head circumference at birth. The nature of medical
      practice in Rochester, Minnesota, and the Mayo Clinic medical records linkage
      system enabled us to provide accurate estimates of medical radiation absorbed
      dose in 9,793 pregnancies of 2,980 women pregnant in Rochester between 1917
      through 1973. Data were controlled for sex of the fetus, duration of pregnancy
      and congenital head abnormalities. It was found that medical ionizing radiation
      in the second and third trimesters of more than 300 mrad were related to
      significantly decreased head circumference. There was no significant effect of
      radiation exposure in the first trimester or periconceptional period. Medical
      ionizing radiation in the second and third trimesters of more than 300 mrad is
      related to a significant yet minimal, decreasing head circumference at birth.
      Maximum effects were seen during the midgestational and second trimester periods.

PMID- 9003978
TI  - Clinical case report: multiple idiosyncratic adverse effects of antiepileptic
      drugs in trisomy 9p.
AB  - We report the case of a mentally retarded 30 y.o. patient with partial trisomy of
      chromosome 9, affected by epilepsy. Following treatment with antiepileptic drugs
      (AEDs), the patient developed several rare complications: after beginning therapy
      with phenytoin, the patient developed pseudolymphoma; after monotherapy with
      carbamazepine (CBZ), the patient thereafter developed myoclonic jerks of upper
      and lower limbs upon awakening; after one year of treatment with valproate (VPA)
      the patient developed clinical and immuno-haematological signs of SLE. Gradual
      withdrawal of AED, obtained clinical remission. The possibility that the
      chromosomal abnormality of the patient was responsible for the three rare
      complications observed during AED therapy is considered.

PMID- 9003979
TI  - Cross-tolerance to acute administration of mu and kappa opioid agonists at the
      spinal cord level in the rat.
AB  - Development of tolerance and cross-tolerance after acute administration of the mu
      agonist morphine and the kappa agonist U-50,488H was assessed in rats, through
      recording of a C-fiber-evoked spinal nociceptive reflex. Rats rendered tolerant
      to morphine (a single dose of 1 mg/kg i.p.) showed, after a 5-hour period,
      tolerance to morphine and cross-tolerance to the kappa-opioid receptor agonist U
      50,488H, as revealed by depressed C-reflex responsiveness. In contrast,
      pretreatment with U-50,488H (a single dose of 1 mg/kg i.p.) rendered tolerant the
      rats to U-50,488H, but the animals did not develop cross-tolerance to morphine.
      Results indicate that acute administration of mu and kappa ligands leads to
      development of unidirectional cross-tolerance in rat spinal cord. This points to
      limitations in using alternated mu and kappa opioid agonists to bypass the
      problem of development of opioid tolerance in chronic pain complaints.

PMID- 9003980
TI  - Enhanced hypnotic suggestibility following application of burst-firing magnetic
      fields over the right temporoparietal lobes: a replication.
AB  - The suggestibility of normal, young men and women as assessed by Spiegel's
      Hypnosis Induction Profile (HIP) before and after weak (1 micro Tesla), burst
      firing magnetic fields were applied for 20 min over the left or over the right
      temporoparietal lobe or both hemispheres; a fourth group received sham treatment.
      Only the group that received the stimulation over the right hemisphere exhibited
      a marked increase in suggestibility (eta = 0.58) following the treatment. These
      results replicate components of several different previous experiments and
      suggest that attribution of symptomatic changes following exposures to weak,
      extremely low frequency magnetic fields, to placebo effects may not be correct.
      Instead, fields whose signatures contain biorelevant information may directly
      affect the neurocognitive processes that are associated with hypnotizability.

PMID- 9003981
TI  - Brief communication: electromagnetic fields improve visuospatial performance and
      reverse agraphia in a parkinsonian patient.
AB  - A 73 year old right-handed man, diagnosed with Parkinson's disease (PD) in 1982,
      presented with chief complaints of disabling resting and postural tremors in the
      right hand, generalized bradykinesia and rigidity, difficulties with the
      initiation of gait, freezing of gait, and mild dementia despite being fully
      medicated. On neuropsychological testing the Bicycle Drawing Test showed
      cognitive impairment compatible with bitemporal and frontal lobe dysfunction and
      on attempts to sign his name he exhibited agraphia. After receiving two
      successive treatments, each of 20 minutes duration, with AC pulsed
      electromagnetic fields (EMFs) of 7.5 picotesla intensity and 5 Hz frequency
      sinusoidal wave, his drawing to command showed improvement in visuospatial
      performance and his signature became legible. One week later, after receiving two
      additional successive treatments with these EMFs each of 20 minutes duration with
      a 7 Hz frequency sinusoidal wave, he drew a much larger, detailed and
      visuospatially organized bicycle and his signature had normalized.
      Simultaneously, there was marked improvement in Parkinsonian motor symptoms with
      almost complete resolution of the tremors, start hesitation and freezing of gait.
      This case demonstrates the dramatic beneficial effects of AC pulsed picotesla
      EMFs on neurocognitive processes subserved by the temporal and frontal lobes in
      Parkinsonism and suggest that the dementia of Parkinsonism may be partly
      reversible.

PMID- 9003982
TI  - Melatonin supplements for aging.

PMID- 9003983
TI  - The recognition potential and word priming.
AB  - The effect of priming on the latency of the recognition potential (RP) was tested
      using rapid stream stimulation. Subjects detected five-letter words in a stream
      of nonword images. Lifting the right index finger signalled detection of a word.
      Rapid responses were rewarded and false alarms were penalized. Just before
      generating an image stream, a computer briefly displayed either the specific
      target word or or five-letter string that indicated the target was any one of ten
      previously studied words. Precise target specification was expected to produce
      more rapid detection than the provision of less definite information. Since the
      RP was thought to reflect the speed of perception, it was predicted that its
      latency would be less when the target word was beforehand than when less specific
      information was provided. The results for 10 subjects confirmed the hypothesis.

PMID- 9003984
TI  - Behavioral characteristics of two rat strains differing in sensitivity to the
      cardiotoxic effect of isoprenaline.
AB  - Behavioral pattern was studied in two inbred strains of rats which have different
      responses to stress. These strains were originally developed from a randomly bred
      Wistar rat colony, according to high or low myocardial cells sensitivity to
      cardiotoxic effect of isoprenaline. One strain is very sensitive to isoprenaline
      cardiotoxicity (IS = isoprenaline sensitive) the other strain is more resistant
      (IR = isoprenaline resistant). In the IR strain the immobilization immersion
      stress causes high incidence of gastric ulcers, while the IS strain is prone to
      heart pathology. In this communication we report the differences in behavior of
      these two rat lines in three tests: open field, intruder's test and Porsolt's
      forced swimming test. The IS animals were passive and anxious in open field test,
      submissive in intruders test and they showed more floating time in Porsolt's
      forced swimming test. The IR rats were active, aggressive and dominant.

PMID- 9003985
TI  - Age differences in hemispheric activation to sensory condition.
AB  - The effects of combinations of bright or dim light and noise levels on hand
      strength, fatigue, motor perseveration, and tapping rate were evaluated in 13
      undergraduate and 13 elderly females. Increments in the intensity of sensory
      conditions produced opposite effects on grip strength at the left, as opposed to
      the right hand. Reliable asymmetry in hand strength (right > left) was observed
      in bright but not dim lighting in the younger group. In the elderly group, the
      extent of asymmetrical hand strength was related to the combination of light and
      noise intensity. Data suggest that increments in sensory conditions may
      differentially activate the cerebral hemispheres of the elderly and younger
      groups affecting grip strength. Results are discussed in relation to the
      hemiaging hypothesis.

PMID- 9003986
TI  - Associations among familial sinistrality, allergies, and developmental language
      disorders.
AB  - Here we report the results of a study that tested what has become known as the
      Geschwind hypothesis (Geschwind & Galaburda, 1987). This study involved 526
      people who were tested by an allergist for IgE-mediated allergies and who filled
      out a 12-item handedness questionnaire that also included questions about
      eyedness, prevalence of left-handedness in the immediate family, and familial
      developmental language problems. A series of log-linear analyses revealed that if
      the definition of "anomalous" included left-handedness and having a first-order
      left-handed relative, one was indeed more likely to be allergic than were those
      not so classified. When the definition of anomalous simply included those
      classified as left-handed, the results were not significant. Parallel findings
      resulted when the criterion variable was the presence of developmental language
      disorders. No evidence was found for relations between allergies and
      developmental language problems.

PMID- 9003987
TI  - Cerebral correlates of anticipated fear: a PET study of specific phobia.
AB  - Cerebral correlates of anticipatory anxiety was studied in 14 women with specific
      snake or spider phobia, and in 6 nonphobic controls. Videofilms with neutral
      scenes were shown during positron emission tomographic measurements of regional
      cerebral blood flow (rCBF). The phobics, but not the controls, anticipated scenes
      with spiders or snakes to appear in the videofilms. This was reflected in higher
      anxiety ratings in the phobics. The primary visual cortex rCBF was lower in
      phobics than controls, while no rCBF differences were found in the other brain
      regions investigated. The results are suggested to indicate inhibition of
      corticogeniculate pathways, in turn representing a neurophysiological correlate
      of avoidant anticipatory coping.

PMID- 9004004
TI  - Virginia Avenelle Henderson RN MA FAAN FRCN: 1897-1996.

PMID- 9004005
TI  - Quality indicators in clinical nursing: a review of the literature.
AB  - The purpose of the present study was, by means of a literature review, to
      describe and analyse the characteristics of clinical indicators used to assess
      and promote quality improvement in nursing care. It was found that a generally
      accepted definition of a clinical indicator is a 'quantitative measure that can
      be used as a guide to monitor and evaluate the quality of important patient care
      and support service activities'. By the seriousness of the event and the degree
      to which it can be avoided, clinical indicators are described as sentinel event
      or rate-based indicators. They can measure structure, process or outcome of care.
      Authors have had different approaches in focus when selecting and developing
      indicators viz. specific aspects of care/nursing diagnosis, medical diagnosis,
      generic aspects of care and clinical areas. These different points of departure
      were influenced by research knowledge, theories/frameworks, or by the opinions of
      patients or staff. The threshold of an indicator is essential when measuring the
      quality of care as it describes a critical level between what is considered good
      or not. Thresholds should be dynamic, realistic, and improve over time. However,
      the literature on how to establish specific thresholds is limited. The review has
      also revealed that there is an uncertainty regarding the use of terms such as
      indicators, standards, norm, criteria and aspects of care.

PMID- 9004006
TI  - Finding your way around qualitative methods in nursing research.
AB  - The intention of this paper is to assist neophyte and traditionally educated
      nurse-researchers to navigate the qualitative research literature with
      understanding. The labelling language describing the central structures of the
      qualitative paradigm will be discussed as the key element to facilitating
      insight. The 'trustworthiness' of this research perspective will also be
      addressed within the context of the nursing research literature.

PMID- 9004007
TI  - Observations on the neglected concept of intervention in nursing research.
AB  - In this paper I will examine the concept of researcher intervention in nursing
      research. I will suggest that the concept is essentially problematic for both
      positivist and qualitative researchers, which may have some bearing upon its
      relative neglect as an area for discussion. I will examine the redundancy of the
      more popular moral frameworks in dealing with the problems raised by intervention
      and suggest that nursing research, being 'messy', requires the articulation of a
      more reflexive and contextual approach. This applies both to moral justification
      and to more pragmatic methodological issues. In the paper I suggest that
      humanistic action research, informed by recent feminist thinking, has potential
      to produce a more creative and clinically relevant future for nursing research
      than is currently so.

PMID- 9004008
TI  - Evaluation of a nurse-led acute pain service. Can clinical nurse specialists make
      a difference?
AB  - This paper attempts to identify the impact of a nurse-led in-patient acute pain
      service (APS) on three areas of concern; pre-operative information, patients self
      reported levels of pain, and analgesics prescribed. It considers the results of a
      baseline survey carried out in 1992 and its replication in 1995, in an attempt to
      assess the impact this service may have had. Results appear to indicate some
      changes in all areas of concern, with significant reductions in reported levels
      of pain and patterns of analgesic prescribing between the two surveys. It
      therefore appears within the constraints of this type of study, that the work of
      the nurse-led APS has had a significant impact on changing outcomes and improving
      quality of patient care.

PMID- 9004009
TI  - The art of nursing in a 'postmodern' context.
AB  - Notions of the 'postmodern' pervade various fields of study, but have rarely been
      applied to the practice and theory of nursing. This paper uses some conceptions
      of the 'postmodern' to remedy this. Though there are many contested usages of the
      term, here 'postmodern' will be used broadly in a periodical sense to trace
      changes in society and culture from the 'modernism' of the 18th and 19th
      centuries to current concerns about 'postmodernism'. How these changes have been
      reflected in nursing practice and nursing theory will be explored. The changing
      use of the term 'modern' to describe up-to-date practice will be addressed in the
      course of this. It is suggested that contextualizing nursing as a social/cultural
      activity in this way offers perspectives which will help us untangle the
      conflicting agendas and issues which form the fabric of the social world in which
      current nursing takes place, enabling us to act more effectively in promoting our
      own professional agendas.

PMID- 9004010
TI  - Health as an individual's way of existence.
AB  - This paper examines health from the viewpoint of Finnish individuals. The goal of
      the study was to understand and describe the human being's health as an
      individual way of existence on the basis of life descriptions. The methodology of
      the study were based on the existentialist phenomenological conception of a human
      being's existence and the essence of knowledge. The study answers the research
      question: How do Finnish adults who have been cared for in hospital experience
      health? The data were collected from 60 persons via free form thematic
      interviews. The data were analysed by applying the grounded theory method. The
      analysis led to the identification of five different ways to experience health.
      To the interviewees, health meant independent coping, drifting with the current
      of life, developing one's personal existence, avoiding threats in one's life
      situation and taking care of the components of one's life situation. The results
      provide a deeper understanding of health within daily life and of a human being
      as a nursing client.

PMID- 9004011
TI  - Parkinson's disease symptoms--patients' perceptions.
AB  - Self-assessment is significant for the accurate evaluation of patient' needs.
      This study examined the frequency and severity of symptoms reported by 39
      patients with Parkinson's disease and compared them with symptoms suggested by
      the literature and by specialists as bothering Parkinson's patients. Four
      categories of symptoms were examined: (a) motor disability or activity loss, (b)
      mental change, (c) psychosocial difficulties, and (d) nonspecific symptoms. The
      findings show that there was correspondence between expert judgements and
      subjects' reports regarding symptoms such as dyskinesia/tremor as well as
      walking, freezing gait, and changing position. Symptoms such as dressing self,
      getting in/out of bed, morning stiffness and deficit in cognitive sequencing,
      which experts described as characteristic of Parkinson's disease patients,
      bothered subjects less. In general, patients mental and psychosocial symptoms
      were higher in their frequencies and perceived severity than problems of
      performing activities of daily living.

PMID- 9004012
TI  - Getting sick and getting well: a qualitative study of aetiologic explanations of
      people with cancer.
AB  - This paper explores lay explanations of developing a cancer disease and
      'recovering' from the disease, both phenomena of importance in understanding how
      information on cancer prevention and recovery is made sense of by non
      professionals. The data derive from interviews conducted with persons diagnosed
      with a malignant disease during 1987 at one hospital in urban Sweden. Forty-six
      patients were interviewed in 1988-1989, and 20 of those surviving were
      interviewed again in 1992. Explanations most often appear to be negotiated forth
      because they are able to fulfil a positive function for the patient in the
      sickness process. Intricate combinations of explanations were found which avoid
      individual blame, provide the possibility of positive influence and allow for
      individual successes. These micro-level explanations are discussed in relation to
      general discourse about prevention of sickness in our culture.

PMID- 9004013
TI  - Survivors of acute leukaemia and highly malignant lymphoma--retrospective views
      of daily life problems during treatment and when in remission.
AB  - Fifty-four former patients, in remission after acute leukaemia or highly
      malignant lymphoma, responded to a questionnaire covering their physical
      problems, their view of the help they received, who was most helpful to them
      during the treatment phase, and the impact of the disease and treatment on their
      current life. Energy loss and nutritional problems were most troublesome during
      the treatment phase, signifying many other physical problems. Patients with acute
      leukaemia had more problems, and thought the care was worse than did patients
      with highly malignant lymphoma. Serious physical problems correlated with low
      satisfaction with practical help received, indicating that the nurses failed to
      meet the needs of those suffering the most. Reduced psychological and sexual
      energy persisted in remission, showed no correlation with the extent of physical
      problems during the treatment phase, but correlated with co-existing problems and
      sensitivity to infections, with a great need for intimate help and counselling
      and with a low sense of coherence. Family relationships were said to have
      improved, while work and finances were negatively affected. The results indicate
      that nursing care should actively focus on physical problems, especially on
      energy loss and nutritional problems. The overwhelming fatigue hinders patients
      in taking physical care of themselves, and may be overlooked by the nurse since
      their motor capability seems intact. The long-term effect of the illness means a
      reduced psychological and sexual energy and a high degree of existential problems
      and sensitivity to infections, which indicates the importance of follow-up care,
      and perhaps especially of counselling for the long-term reactions and disturbance
      of equilibrium.

PMID- 9004014
TI  - A comparison study of children with sickle cell disease and their non-diseased
      siblings on hopelessness, depression, and perceived competence.
AB  - The purpose of this comparison study was to explore the extent to which
      hopelessness and self-perceptions of competence are associated with depression in
      a community population of children with sickle cell disease compared to their non
      diseased siblings. Subjects were African-American children drawn randomly from
      the case management programme at the L.D. Barksdale Sickle Cell Anemia
      Foundation. Depression scores were higher for the non-diseased siblings. The
      children with sickle cell disease scored lower on the perceived physical
      competence scale. Recommendations for practice include increasing hope, improving
      relationships, monitoring depression in patients and their siblings, and
      monitoring perceptions of cognitive, social, physical, and general self-worth.

PMID- 9004016
TI  - Social support: a conceptual analysis.
AB  - Using the methodology of Walker and Avant, the purpose of this paper was to
      identify the most frequently used theoretical and operational definitions of
      social support. A positive relationship between social support and health is
      generally accepted in the literature. However, the set of dimensions used to
      define social support is inconsistent. In addition, few measurement tools have
      established reliability and validity. Findings from this conceptual analysis
      suggested four of the most frequently used defining attributes of social support:
      emotional, instrumental, informational, and appraisal. Social network, social
      embeddedness, and social climate were identified as antecedents of social
      support. Social support consequences were subsumed under the general rubric of
      positive health states. Examples were personal competence, health maintenance
      behaviours, effective coping behaviours, perceived control, sense of stability,
      recognition of self-worth, positive affect, psychological well-being, and
      decreased anxiety and depression. Recommendations for future research were made.

PMID- 9004015
TI  - The caring dimensions inventory (CDI): content validity, reliability and scaling.
AB  - Caring is an elusive phenomenon but this should not prevent the development and
      validation of reliable quantitative tools for studying this concept in large
      samples of nurses. The present paper reports on the content analysis of a
      questionnaire called the Caring Dimensions Inventory (CDI). The CDI was content
      validated in terms of existing conceptualizations of caring and research in this
      area and also in terms of a nursing taxonomy and its representation in popular
      United Kingdom nursing publications. The CDI was administered to a large sample
      of nurses working in Scotland and data were obtained from 1430 qualified and
      student nurses. The internal consistency of the CDI items related to perceptions
      of caring was established and the scalability of a sub-set of CDI items was
      demonstrated. The CDI scale was related to the constructs of age and sex of
      respondents. Possibilities for further analysis and development of the CDI are
      discussed.

PMID- 9004017
TI  - Liaison mental health nursing: origins, definition and prospects.
AB  - Liaison mental health nursing is an evolving specialist area of mental health
      nursing in the United Kingdom (UK). It has many similarities with 'psychiatric
      consultation liaison nursing' practised in the United States of America (USA),
      but there have been differences in its development. It is well established in
      general health settings where psychological problems are most apparent, such as
      accident and emergency services and oncology. However, it lacks clear definition.
      The author addresses this by examining the literature for evidence of how the
      role has developed, and how it is currently described. The position of liaison
      mental health practice within nursing is discussed, and also its relationship to
      liaison psychiatry. The theoretical base of this specialty may be seen as an
      integration of biological, psychological and sociological perspectives. There is
      no current programme of training for liaison mental health nurses, and this is
      likely to inhibit its recognition as a specialty in the UK. As interest grows in
      psychosocial aspects of physical health, liaison mental health nursing has the
      potential to provide a focus for research within nursing. Areas for further
      development are reviewed, and a research agenda is proposed.

PMID- 9004018
TI  - Caring for a demented elderly person--burden and burnout among caregiving
      relatives.
AB  - Fifty-two family caregivers for demented elderly people were investigated for
      burden and burnout experiences. A structured burden questionnaire and the Burnout
      Measure were used. Burnout is described in relation to the caregiver's gender,
      age, family relationship and the demented person's living place. Older wives and
      daughters were the most likely to report burnout in their lives. Some siblings
      and daughters-in-law also risked developing burnout. Regression analysis showed
      that limitation in social life, poor health and a lack of positive outlook on
      caring were the most important independent variables explaining variance in
      burnout among caregivers. There was no difference in burnout experiences between
      caregivers having their demented elderly person living at home and those having
      them in an institution.

PMID- 9004019
TI  - Snapshots of experience: vignettes from a nursing home.
AB  - The specific aim of this research project was to examine and describe the
      experience of living in a nursing home for six people of 80 years and older.
      'Visit' is presented as a means of developing nursing knowledge. This research
      method is founded on the belief that the act of nursing involves the development
      of a relationship, and was created out of the author's desire for a relational
      research method. Philosophical support for the method is provided by Maurice
      Merleau-Ponty's existentialism, Sally Gadow's existential advocacy, and Jean
      Watson's Human Caring Theory. Authenticity is proposed as an alternative to the
      concepts of reliability and validity for judging the scientific merit of the
      method. Whether the nursing role is researcher, practitioner or educator, each
      person's unique and inexhaustible story provides the basis for nursing care.
      Nurse researchers using 'Visit' as a method of inquiry can illustrate these
      unique differences through a story, through the images or pictures each
      individual creates with his or her own words.

PMID- 9004020
TI  - The trait and process of resilience.
AB  - Resilience is the ability of people to 'spring back' in the face of adversity. It
      is an important concept for nurses as we endeavour to assist individuals to meet
      the challenges of living with illness and ageing. Researchers from many
      disciplines in both the social and health sciences have investigated resilience
      of individuals throughout the life cycle in a variety of situations related to
      health as well as other life events. Some researchers have investigated
      resilience as a trait of individuals while other view resilience as a process.
      This article reviews the current literature on resilience from many disciplines
      and discusses implications for nursing practice and research.

PMID- 9004021
TI  - Advocacy in nursing--a review of the literature.
AB  - Patient/client advocacy has been claimed as a new role for the professional
      nurse. This paper presents a critical review of the literature on advocacy in
      nursing. After briefly outlining the conditions which may have instigated the
      need for patient advocacy, meanings and models of advocacy are discussed. It is
      argued that although there are many examples of the advocacy role in health care,
      models proposed for the nurse as advocate are indeterminate which leads to
      multiple interpretations and lack of clarity in operationalizing advocacy. Much
      of the literature focuses on justification arguments for claiming the advocacy
      role. Key themes are outlined and include: patient advocacy as a traditional
      role, nurses are in the best position in the health care team, nurses have the
      knowledge to advocate and finally nurses and patients can be partners in
      advocacy. However, critical examination reveals many counter-arguments to the
      above claims and finally concludes that advocacy is a potentially risky role to
      adopt. It is argued that support systems are inadequate except in low-risk
      situations and ultimately acts of advocacy remain a moral choice for the
      individual nurse. Finally the need to conduct research into the interpretation of
      the patient advocate role by nurses in the United Kingdom is highlighted.

PMID- 9004022
TI  - 'Mom, I have something to tell you'--disclosing HIV infection.
AB  - This paper explores the experience of disclosing HIV infection to family members.
      Information was obtained from secondary analysis of interviews conducted with 10
      HIV-positive men and women. Learning that one is HIV-positive is a traumatic
      event, and disclosing this to family members can be difficult. Findings from this
      study suggest that family members generally overcome their own feelings and
      provide the infected individual with love and support. However, the resultant
      stress on the family may precipitate a crisis as secrets are brought into the
      open. Implications for nursing practice are addressed.

PMID- 9004023
TI  - A critical review of the literature on sharps injuries: epidemiology, management
      of exposures and prevention.
AB  - This article reviews the literature related to the epidemiology, prevention and
      management of sharps injuries in health care workers, particularly nurses, and
      the subsequent risk of harm. The studies are reviewed chronologically, beginning
      with the efforts to reduce sharps injuries by changing behaviours, followed by
      the introduction of barriers to protect the caregiver, and finally, the
      engineering of safer products. Initial efforts to prevent sharps injuries focused
      on placing rigid, disposal containers at the site where sharps were used and
      instructing health care workers to refrain form the practice of recapping. When
      these interventions were shown to alter the type, but not the overall number, of
      sharps injuries, alternative measures were sought. This search intensified with
      the increasing evidence of the small, but measurable, risk of the transmission of
      human immunodeficiency virus from sharps injuries. The current knowledge of the
      factors related to sharps injuries has been collected primarily through
      retrospective surveillance. This surveillance has been conducted primarily in
      hospital settings and has focused on the type of sharp and the purpose for which
      it was used rather than prospective research. Research is now needed to elucidate
      the organizational and behavioural factors leading to sharps injury both within
      the hospital as well as other health care settings. The implications for nursing
      practice are discussed.

PMID- 9004024
TI  - Acting at a disaster site: experiences expressed by Swedish nurses.
AB  - In a previous study the knowledge and views of nursing students on how they
      thought nurses, both in their professional role and as private persons, should
      act at a disaster site were evaluated. In the present study the practical
      functional role and experiences of nurses (n = 16) in two major disaster
      situations (one 'load and go' and one 'stay and play' type of emergency
      situation) were assessed from personal interviews along a standardized
      questionnaire. Nurses more routinely involved in emergency care and nurses with
      no or limited previous practical experience of disaster nursing were included in
      the study. Leadership-type actions, i.e. a systematic way of attempting to survey
      and to comprehend the situation, what has happened, and how many injured there
      may be at the site of the accident, were reported by most of the experienced
      nurses, while inexperienced nurses were involved mainly in the immediate care of
      injured according to directions given by more experienced members of the
      emergency team. Readiness for action, reflected by having a feeling of being
      prepared for work at the disaster site, was experienced more often by nurses with
      considerable previous experience of disaster nursing than by nurses with limited
      experience. Negative experiences, such as feelings of being insufficient, of
      unreality, mental strain, and problems in understanding the organization, were
      commonly mentioned by the inexperienced nurses. The present study stresses the
      importance, for all types of nurses, of more systematic training in disaster
      nursing.

PMID- 9004026
TI  - Sexual health promotion and nursing.
AB  - The HIV epidemic provides continued impetus for effective sexual health
      promotion. Sexual health promotion in nursing practice has traditionally been
      equated to prevention at primary, secondary and tertiary levels. Increasing
      demands on practitioners to address the psycho-social aspects of sexual health,
      together with a greater emphasis on primary prevention, is leading to the
      adoption of theoretical paradigms from the behavioural sciences and the
      increasing use of counselling skills. The limitations of individualist
      interventions for primary prevention are explored, and the assumption that health
      care professionals are effective promoters of sexual health is questioned. The
      importance of placing sexual health and nursing practice within a wider social,
      political and cultural context is emphasized.

PMID- 9004025
TI  - Sexual harassment in nursing.
AB  - Sexual harassment is a problem faced by women in the workplace which can lead to
      adverse psychological consequences as well as impaired work performance. Sexual
      harassment is about the abuse of power and status rather then merely being about
      sex per se and has to be viewed in the context of institutionalized male power.
      Although there is a relative dearth of research, there is increasing evidence
      that sexual harassment of nurses is common and that it can have adverse effects
      on nurses physical and psychological health as well as a direct impact on patient
      care. Nursing, by its very nature of having to care for patients bodily needs,
      transgresses normal social rules regarding bodily contact. This is exploited by
      the perpetrator who relies on nurses' caring attitude to be able to harass. A
      descriptive model of the processes involved in harassment is presented which
      offers the possibility of being able to intervene at a number of points in the
      process. Interventions need to be aimed at both individual and organizational
      levels if there is to be a prospect of reducing a major occupational stressor for
      nurses.

PMID- 9004027
TI  - The practice of health education in acute care settings in Hong Kong: an
      exploratory study of the contribution of registered nurses.
AB  - A multiple case study design was used to explore the practice of health education
      in acute care settings in Hong Kong. Two case studies, a medical ward and a
      surgical ward, were selected to reflect the real setting in which nurses carry
      out health education in acute care. Data collection methods involved the use of
      non-participant observation and semi-structured interviews. Seven nurses and
      eight patients were interviewed to explore their understanding of health
      education concepts, the use made in the wards of health education and the factors
      influencing such practice in the acute settings. Individual and cross-case
      analysis showed that respondents' understanding of the concept of health
      education was limited to patient information-giving. Although the importance of
      health education in acute patient care was acknowledged, the degree to which
      health education featured in nurses' practice was minimal. Many available
      opportunities for health education were missed and factors such as nurses' busy
      ness and the associated lack of time and staff were identified as influencing
      health education practice in these acute care settings. Implications for practice
      and future studies were discussed in the light of these findings.

PMID- 9004028
TI  - Nursing culture--some viewpoints.
AB  - The concept of culture is closely interwoven with the values espoused by a
      community. Culture is a deep structure that finds expression in people's
      knowledge, beliefs, convictions, morals, and laws. A few possible ways of
      approaching the culture of nursing are provided by rituals, gender and power.

PMID- 9004029
TI  - The practice-based context of educational innovation: nurse and midwife
      preparation in Scotland.
AB  - The use of an illuminative approach to the national evaluation of the first 18
      months of Project 2000 nurse and pre-registration midwifery education in Scotland
      has facilitated the generation of data about the contexts in which the new
      programmes function. The aim of this paper is to present some of the data
      generated from programme participants about the conditions students experience in
      practice-based learning experiences. The reported issues are direct or indirect
      effects of policy initiatives and service reforms. The current climate of change
      in health care provision has fostered a limited number of developments which are
      consistent with the aspirations of the new programmes and which offer highly
      valued learning experiences to students. More often however the reforms have
      served to frustrate the intent of the programmes to offer students experiences
      which are patient-centred, holistic-care and health oriented.

PMID- 9004030
TI  - Retention of nursing students with English as a second language.
AB  - The purposes of this study were to: (a) determine nursing students' perceptions
      of the learning activities which contribute the most to their knowledge and
      skills; (b) determine students' perceptions of their learning difficulties; (c)
      compare the perceptions of English as a second language (ESL) and non-ESL
      students; (d) determine nursing faculty perceptions of ESL students' learning
      difficulties; (e) compare the perceptions of ESL students and faculty; and (f)
      identify needs for educational and/or supportive programmes for faculty and
      students. Differences in perceptions of faculty and students regarding areas of
      difficulty and students' needs may influence the services provided to students
      and therefore contribute to their lack of success and attrition. A questionnaire
      was given to students in the first and second years of the University of British
      Columbia (UBC)/Vancouver Hospital (VH) Nursing Programme to collect data
      regarding their high school and post-secondary education, date of arrival in
      Canada, first language, and their perceptions of helpfulness and difficulty of
      learning activities. A similar questionnaire was given to faculty members working
      with these students to collect data about their perceptions of areas of
      difficulty and activities that contribute the most to the learning of ESL
      students. Data analysis consisted of t-tests for statistical comparison of the
      responses of ESL and non-ESL students, and ESL students and faculty. The results
      indicated statistically significant differences between the perceptions of
      faculty and ESL students, particularly in the areas of difficulty. The need for
      educational programmes for both faculty and students was identified.

PMID- 9004031
TI  - Axonal targeting of agrin in cultured rat dorsal horn neurons.
AB  - Agrin, a synaptic basal lamina protein synthesized by motoneurons is involved in
      the aggregation of nicotinic acetylcholine receptors (nAchRs) at the
      neuromuscular junction. Agrin transcripts are broadly expressed in the central
      nervous system (CNS) including non-cholinergic regions. This wide distribution of
      agrin mRNAs raises the question of its function in these areas. To approach this
      question, we analysed the expression and cellular distribution of agrin in
      primary cultures of rat embryonic dorsal horn neurons. Polymerase chain reaction
      analysis demonstrated that the four agrin isoform (B0, B8, B11, B19) mRNAs are
      expressed as early as 4 days in vitro, before the formation of functional
      synaptic contacts. Western blots also showed that agrin-like proteins are
      secreted in conditioned medium from 7 days cultures. We analysed the subcellular
      distribution of agrin by double immunolabeling and fluorescence microscopy. We
      found that agrin is synthesized by almost all neurons and was present in the
      somata and in the axons but not in dendrites within the sensitivity of the
      detection. This intra-axonal localisation of agrin could only be seen after
      permeabilization. Furthermore, agrin immunoreactive axons were found adjacent to
      gephyrin, the postsynaptic glycine receptor-associated protein. Altogether, our
      results suggest that, as established at the neuromuscular junction, agrin may be
      involved in pre- to postsynaptic interactions in the central nervous system.

PMID- 9004032
TI  - GLUT4 in cultured skeletal myotubes is segregated from the transferrin receptor
      and stored in vesicles associated with TGN.
AB  - There is little consensus on the nature of the storage compartment of the glucose
      transporter GLUT4, in non-stimulated cells of muscle and fat. More specifically,
      it is not known whether GLUT4 is localized to unique, specialized intracellular
      storage vesicles, or to vesicles that are part of the constitutive endosomal
      lysosomal pathway. To address this question, we have investigated the
      localization of the endogenous GLUT4 in non-stimulated skeletal myotubes from the
      cell line C2, by immunofluorescence and immunoelectron microscopy. We have used a
      panel of antibodies to markers of the Golgi complex (alpha mannosidase II and
      giantin), of the trans-Golgi network (TGN38), of lysosomes (lgp110), and of early
      and late endosomes (transferrin receptor and mannose-6-phosphate receptor,
      respectively), to define the position of their subcellular compartments. By
      immunofluorescence, GLUT4 appears concentrated in the core of the myotubes. It is
      primarily found around the nuclei, in a pattern suggesting an association with
      the Golgi complex, which is further supported by colocalization with giantin and
      by immunogold electron microscopy. GLUT4 appears to be in the trans-most
      cisternae of the Golgi complex and in vesicles just beyond, i.e. in the
      structures that constitute the trans-Golgi network (TGN). In myotubes treated
      with brefeldin A, the immunofluorescence pattern of GLUT4 is modified, but it
      differs from both Golgi complex markers and TGN38. Instead, it resembles the
      pattern of the transferrin receptor, which forms long tubules. In untreated
      cells, double staining for GLUT4 and transferrin receptor by immunofluorescence
      shows similar but distinct patterns. Immunoelectron microscopy localizes
      transferrin receptor, detected by immunoperoxidase, to large vesicles, presumably
      endosomes, very close to the GLUT4-containing tubulo-vesicular elements. In
      brefeldin A-treated cells, a network of tubules of approximately 70 nm diameter,
      studded with varicosities, stains for both GLUT4 and transferrin receptor,
      suggesting that brefeldin A has caused fusion of the transferrin receptor and
      GLUT4-containing compartments. The results suggest that GLUT4 storage vesicles
      constitute a specialized compartment that is either a subset of the TGN, or is
      very closely linked to it. The link between GLUT4 vesicles and transferrin
      receptor containing endosomes, as revealed by brefeldin A, may be important for
      GLUT4 translocation in response to muscle stimulation.

PMID- 9004034
TI  - Differentiation and integrity of cardiac muscle cells are impaired in the absence
      of beta 1 integrin.
AB  - Cellular interactions with substrata of the microenvironment are one of the major
      mechanisms for differentiation and morphogenesis. Many of these interactions are
      mediated via the beta 1 integrin subfamily of cell surface receptors, which are
      believed to transduce signals upon cell adhesion. We have used beta 1 integrin
      deficient embryonic stem cells to test their ability to differentiate into
      cardiac muscle cells. We show here by several approaches that beta 1 integrin is
      important for normal cardiogenesis. First, the in vitro differentiation of beta 1
      integrin-deficient embryonic stem cells into cardiac muscle cells is retarded.
      This is demonstrated by the delayed expression of cardiac muscle-specific genes
      and action potentials. Second, the specification of cardiac precursor cells into
      pacemaker-, atrial- and ventricular-like cells is significantly impaired in beta
      1 integrin-deficient cells. The occurrence of atrial- and ventricular-like cells
      is reduced and transient. Only cells exhibiting peacemaker-like action potentials
      of high frequency and arrhythmias survive. Third, the sarcomeric architecture is
      incomplete and disarranged in the absence of beta 1 integrin. Fourth, beta 1
      deficient embryonic stem cells can contribute to the developing heart in
      chimaeric mice but many areas with beta 1-null cells contain cell debris. The
      number of beta 1-null cells decrease from prenatal to postnatal stages and is
      lost completely in 6-month-old hearts. Thus, we conclude that interactions with
      the extracellular matrix via beta 1 integrin is necessary for differentiation and
      the maintenance of a specialized phenotype of cardiac muscle cells.

PMID- 9004033
TI  - Subcellular localization of Trypanosoma cruzi glycoprotein Gp72.
AB  - We have investigated the subcellular location of the Trypanosoma cruzi surface
      glycoprotein, Gp72, by introducing epitope-tagged copies of gp72 null-mutant
      cells. A tagged Gp72, containing three tandemly repeated copies of a human
      influenza hemagglutinin nonapeptide (HA) adjacent to the mature Gp72 amino
      terminus, was able to complement the null mutant phenotype, as well as being
      recognized in Western blots by both anti-HA antibody and the carbohydrate
      specific monoclonal antibody WIC29.26. Integration of this epitope-tagged gp72
      into the chromosomal gp72 locus produced a clonal cell line, 72HAN3.1G7, which
      was used for studies of the subcellular location of the epitope-tagged Gp72.
      Indirect immunofluorescence microscopy of fixed 72HAN3.1G7 epimastigotes showed
      that GP72 was evenly distributed over the cell body and somewhat concentrated in
      the proximal region of the flagellum. No fluorescence could be detected in the
      distal tip of the flagellum. Immunoelectron microscopy of fixed 72HAN3.1G7
      epimastigotes revealed that Gp72 was predominantly membrane-associated and
      located on the cell surface. Indirect immunofluorescence microscopy of live
      72HAN3.1G7 epimastigote cells showed a similar pattern of fluorescence on the
      flagellum, but no fluorescence was detected on the cell body, which was
      attributed to masking by other cell-surface components. Indirect
      immunofluorescence microscopy of fixed 72HAN3.1G7 amastigotes revealed that Gp72,
      which has long been considered to be expressed only in epimastigotes and
      metacyclic trypomastigotes, can be expressed in amastigotes, but it no longer
      contains the WIC29.26 carbohydrate epitope.

PMID- 9004035
TI  - Deficiency of protein phosphatase 2A uncouples the nuclear and centrosome cycles
      and prevents attachment of microtubules to the kinetochore in Drosophila
      microtubule star (mts) embryos.
AB  - A Drosophila strain, carrying a P[lacW] element in the promoter of the protein
      phosphatase 2A (PP2A) catalytic subunit gene at chromosomal location 28D, has
      been identified using plasmid rescue of the P element and adjoining genomic DNA
      in Escherichia coli. Reversion mutagenesis was employed to demonstrate that the
      observed phenotype of the Drosophila strain was due to a single P[lacW] element
      insertion at 28D and to create three deficiency strains at this locus. Drosophila
      heterozygous for P[lacW]28D have reduced levels of PP2A mRNA and reduced PP2A
      catalytic activity against four different substrates compared to wild type, while
      homozygotes are deduced to have approximately 20% of wild-type PP2A activity.
      P[lacW]28D homozygotes, termed microtubule star (mts), die in embryo-genesis
      around the time of cellularisation, exhibiting over-condensed chromatin and a
      block in mitosis between prophase and the initiation of anaphase. Multiple
      centrosomes are visible in cellularised embryos, suggesting that PP2A may play a
      role in coupling the nuclear and centrosome cycles. When embryos arrest just
      prior to cellularisation, disorganised elongated arrays of microtubules radiate
      from centrosomes in all directions, but they are rarely associated with any DNA,
      suggesting that PP2A is required for the attachment of microtubules to
      chromosomal DNA at the kinetochore.

PMID- 9004036
TI  - Expression of a dominant negative cadherin mutant inhibits proliferation and
      stimulates terminal differentiation of human epidermal keratinocytes.
AB  - Cell adhesion molecules are not only required for maintenance of tissue
      integrity, but also regulate many aspects of cell behaviour, including growth and
      differentiation. While the regulatory functions of integrin extracellular matrix
      receptors in keratinocytes are well established, such functions have not been
      investigated for the primary receptors that mediate keratinocyte intercellular
      adhesion, the cadherins. To examine cadherin function in normal human epidermal
      keratinocytes we used a retroviral vector to introduce a dominant negative E
      cadherin mutant, consisting of the extracellular domain of H-2Kd and the
      transmembrane and cytoplasmic domains of E-cadherin. As a control a vector
      containing the same construct, but with the catenin binding site destroyed, was
      prepared. High levels of expression of the constructs were achieved; the dominant
      negative mutant, but not the control, formed complexes with alpha-, beta- and
      gamma-catenin. In cells expressing the dominant negative mutant there was a 5
      fold decrease in the level of endogenous cadherins and a 3-fold increase in the
      level of beta-catenin. Cell-cell adhesion and stratification were inhibited by
      the dominant negative mutant and desmosome formation was reduced. Expression of
      the mutant resulted in reduced levels of the alpha 2 beta 1 and alpha 3 beta 1
      integrins and increased cell motility, providing further evidence for cross-talk
      between cadherins and the beta 1 integrins. In view of the widely documented loss
      of E-cadherin in keratinocyte tumours it was surprising that the dominant
      negative mutant had an inhibitory effect on keratinocyte proliferation and
      stimulated terminal differentiation even under conditions in which intercellular
      adhesion was prevented. These results establish a role for cadherins in
      regulating keratinocyte growth and differentiation and raise interesting
      questions as to the relative importance of cell adhesion-dependent and 
      independent mechanisms.

PMID- 9004037
TI  - The polarity of the plasma membrane protein RET-PE2 in retinal pigment epithelium
      is developmentally regulated.
AB  - The retinal pigment epithelium (RPE) differs from other epithelia in that the
      apical surface is not free; instead, it interacts with both photoreceptors and a
      specialized extracellular material, the interphotoreceptor matrix. Biochemical
      characterization of the apical and basolateral surfaces of RPE in adult rat eye
      cups, using a novel in situ biotinylation assay, revealed very different protein
      compositions and identified a major surface antigen, RET-PE2, with a
      predominantly apical distribution (approximately 74%). The apical polarity of RET
      PE2 was confirmed by immunofluorescence and laser scanning confocal microscopy.
      In striking contrast, RET-PE2 antigen was preferentially basolateral in primary
      cultures derived from adult rat RPE and in an immortalized RPE cell line (RPE-J).
      Under all conditions, RET-PE2 was highly soluble in Triton X-100 (> 81% at 4
      degrees C), suggesting that its redistribution was not dependent on changes in
      cytoskeletal interactions. Analysis of the localization of RET-PE2 in normal rats
      at postnatal (PN) days 1, 7, and 14 indicated that RET-PE2 redistributes from
      predominantly basolateral to predominantly apical during that time. Since
      photoreceptors develop during the first two weeks after birth in the rat, our
      results suggest that the apical redistribution of RET-PE2 is dependent on the
      establishment of adult interactions between the RPE and the neural retina and/or
      the interphotoreceptor matrix, either via direct contacts or through alterations
      in the intracellular sorting patterns of RPE cells.

PMID- 9004039
TI  - Disruption of the vimentin intermediate filament system during adipose conversion
      of 3T3-L1 cells inhibits lipid droplet accumulation.
AB  - During the differentiation of 3T3-L1 pre-adipocytes, vimentin intermediate
      filaments are reorganized to form cage-like structures around the nascent lipid
      droplets. Initial studies with 3T3-L1 cells indicated that aggregation of
      vimentin filaments by nocodazole treatment during or shortly after induction of
      adipose conversion dramatically reduced the lipid droplet content of 3T3-L1 cells
      96-120 hours after induction. Specific but transient disruption of vimentin
      following anti-IFA antibody injection also resulted in a decrease in lipid
      droplet formation in differentiating cells. To specifically and stably affect
      filament organization, 3T3-L1 cells lines were established by transfection with a
      glucocorticoid-regulatable, dominant negative mutant vimentin cDNA expression
      plasmid. Treatment of these cells (83 delta C) with dexamethasone resulted in
      expression of vimentin with a carboxyl-terminal deletion, which led to the
      disruption of the endogenous filament network. Induction of adipose conversion in
      83 delta C cells lead to the formation of lipid droplets comparable to those seen
      in untransfected 3T3-L1 cells. Addition of dexamethasone during the adipose
      conversion of 83 delta C cells did not affect the induction of the marker enzyme
      glycerol-3-phosphate dehydrogenase or the incorporation of [14C]palmitate into
      triglycerides during a 10 minute pulse label. There was, however, a failure to
      form prominent lipid droplets and to accumulate [14C]palmitate-labeled
      triglycerides. Pulse-chase experiments indicated that the failure of these cells
      to accumulate triglyceride was associated with an increased rate of turnover.
      These studies indicate that vimentin filaments provide a function that influences
      lipid stability during adipose conversion of 3T3-L1 cells.

PMID- 9004038
TI  - CD24 (heat stable antigen, nectadrin), a novel keratinocyte differentiation
      marker, is preferentially expressed in areas of the hair follicle containing the
      colony-forming cells.
AB  - We have isolated, by subtractive and differential hybridization from a library
      constructed from keratinocyte colony-forming cells (K-CFCs), a cDNA coding for
      the rat CD24 (nectadrin, heat stable antigen). CD24, a glycoprotein thought to be
      involved in cell-cell adhesion and signalling, is highly expressed in
      keratinocytes located in the bulge area of the rat vibrissa which contains the
      most K-CFCs. CD24 is also expressed in the outer epithelial sheath of human hair
      follicles and in glabrous epidermis. However, its expression is not restricted to
      K-CFCs as demonstrated by cell sorting experiments, and it is thus not a specific
      marker of clonogenic keratinocytes. Rather, its preferential distribution in
      keratinocytes located in the most innervated area of the rat vibrissal follicle,
      i.e., the bulge, suggests that is function could be related to the tactile role
      of the hair follicle.

PMID- 9004040
TI  - A membrane-associated protein complex with selective binding to the clathrin coat
      adaptor AP1.
AB  - Adaptors are the membrane-binding components of clathrin-coated vesicles. The
      interaction of the trans-Golgi coat adaptor AP1 with membrane-associated proteins
      was analyzed by affinity chromatography. Proteins of 83 and 52 kDa bound
      specifically to the core domain of AP1 and showed no interaction with AP2 or
      other clathrin-coated vesicle proteins. The AP1-binding proteins were tightly
      membrane-associated, though behaved as peripheral membrane proteins. They were
      detected in membranes depleted of clathrin-coated vesicles and not in coated
      vesicles, suggesting that the interaction of these proteins with AP1 may precede
      coated vesicle budding. Co-fractionation of the AP1-binding proteins with trans
      Golgi network membrane was also observed. Upon gel filtration, both AP1-binding
      proteins eluted in a high molecular mass complex which was labile at high
      concentrations of Tris. The 83 kDa protein bound to AP1 affinity resin in the
      absence of the 52 kDa protein. In contrast, the separated 52 kDa protein did not
      bind AP1, suggesting that the 83 kDa protein is the AP1-binding component of the
      complex. Characterization of this protein complex defines a novel membrane
      associated component that specifically interacts with AP1 and may contribute to
      its function in forming clathrin-coated vesicles.

PMID- 9004041
TI  - Cadherin binding sites of plakoglobin: localization, specificity and role in
      targeting to adhering junctions.
AB  - Plakoglobin directly interacts with cadherins and plays an essential role in the
      assembly of adherens junctions and desmosomes. Recently we have reported that
      multiple cadherin binding sites are localized along the arm repeat region of
      plakoglobin. To demonstrate functionally and specificity of these sites in vivo
      we constructed a set of chimeric proteins containing a plakoglobin sequence fused
      with the transmembrane vesicular protein synaptophysin. Plakoglobin fused
      upstream or downstream from synaptophysin (PgSy and SyPg, chimeras, respectively)
      is exposed on the cytoplasmic surface of synaptic-like vesicles and is able to
      associate with E-cadherin, and with two desmosomal cadherins, desmoglein and
      desmocollin. Moreover, plakoglobin targets these vesicles to cell-cell junctions.
      Insertion of synaptophysin within plakoglobin (PSyG chimeras) can interfere with
      cadherin binding of the resulting chimeric proteins, dependent on the position of
      the insertion. Insertion of synaptophysin in the first three arm repeats
      selectively inactivates plakoglobin binding to desmoglein and desmocollin. An
      insertion of synaptophysin within the next two repeats inactivates E-cadherin and
      desmocollin binding but not desmoglein binding. This localization of the
      desmoglein and E-cadherin binding sites was further confirmed by replacement of
      plakoglobin arm repeats with the corresponding sequence derived from the
      plakoglobin homologue, beta-catenin, and by deletion mutagenesis. Insertion of
      synaptophysin in most sites within arm repeats 6-13 does not change plakoglobin
      binding to cadherins. It does, however, strongly inhibit association of the
      resulting vesicles either with desmosomes and adherens junctions or with
      desmosomes only. Using in vitro binding assays we demonstrate that arm repeats 6
      13 contain two cryptic cadherin binding sites that are masked in the intact
      protein. These observations suggest that the arm repeat region of plakoglobin is
      comprises two functionally distinct regions: the 1/5 region containing desmoglein
      and E-cadherin specific binding sites and the 6/13 region implicated in targeting
      of plakoglobin/cadherin complexes into junctional structures.

PMID- 9004042
TI  - Cellulose microfibrils, cell motility, and plasma membrane protein organization
      change in parallel during culmination in Dictyostelium discoideum.
AB  - Prestalk cells of Dictyostelium discoideum contribute cellulose to two distinct
      structures, the stalk tube and the stalk cell wall, during culmination. This
      paper demonstrates by freeze fracture electron microscopy that two distinct types
      of intramembrane particle aggregates, which can be characterized as cellulose
      microfibril terminal complexes, occur in the plasma membranes of cells
      synthesizing these different forms of cellulose. The same terminal complexes were
      observed in situ in developing culminants and in vitro in monolayer cells induced
      to synthesize the two types of cellulose. We propose that cessation of cell
      motility is associated with a change in packing and intramembrane mobility of the
      particle aggregates, which cause a change in the nature of the cellulose
      synthesized. The terminal complexes are compared to those described in other
      organisms and related to the previous hypothesis of two modes of cellulose
      synthesis in Dictyostelium.

PMID- 9004043
TI  - Most of centrin in animal cells is not centrosome-associated and centrosomal
      centrin is confined to the distal lumen of centrioles.
AB  - Centrin is a member of the calcium-binding EF-hand protein superfamily present in
      centrosomes of widely divergent species. Investigating the cellular distribution
      of human centrin by both immunofluorescence and cell fractionation, we report
      that centrin is biochemically complex in human cells, displaying as much as ten
      isoforms in 2-D electrophoresis. This suggests that centrin may be subject to
      multiple regulations. Strikingly, more than 90% of centrin is not associated with
      the centrosome fraction. The centrosome-associated centrin, however, displays a
      specific pattern in 2-D electrophoresis and is concentrated within the distal
      lumen of the centrioles, where a complex structure has been previously described.
      This precise localization allows the resolution of centrioles at the optical
      level throughout the cell cycle and provides a valuable tool for monitoring
      centriole duplication. To get insights on centrin function, we performed
      injection experiments of recombinant heterologous centrin in two-cell stage frog
      embryos in an attempt to produce dominant negative effects. We report that green
      algae and human centrin delay cleavage and promote the formation of abnormal
      blastomeres in which the distribution of microtubule asters and of nuclei is
      dramatically impaired. This suggests that centrin could be involved in the
      centrosome reproduction cycle, in the coordination of cytoplasmic and nuclear
      division or in cytokinesis.

PMID- 9004045
TI  - Expression and changing distribution of the human transferrin receptor in
      developing Drosophila oocytes and embryos.
AB  - In order to understand better the membrane systems in a developing Drosophila
      oocyte, the human transferrin receptor has been expressed there. This was
      achieved using the armadillo promoter combined with K10 or oskar trailer
      sequences; these enable the messenger RNA to be transcribed in nurse cells and
      then transported to, and translated in, oocytes. This is the first exogenous
      protein to be expressed in oocytes. At stage 8, the transferrin receptors are
      mainly concentrated towards the posterior pole of the oocyte and are associated
      with large cytoplasmic vesicles; when combined with the shibire mutation the
      transferrin receptors are transferred to the oolemma, demonstrating that they
      participate in an endocytic cycle. At stage 10, the transferrin receptors are
      localised either to the anterior margin of the oocyte or to the posterior pole,
      depending on where the mRNA is located. In newly laid eggs, all the transferrin
      receptors are found in large cytoplasmic vesicles. The results reveal remarkable
      sorting processes which occur as oocytes mature and show that ring canals, which
      separate the oolemma from nurse cell plasma membranes, act as barriers to prevent
      components in these two compartments from intermixing.

PMID- 9004044
TI  - A novel structural component of the Dictyostelium centrosome.
AB  - The microtubule-organizing center of D. discoideum is a nucleus-associated body
      (NAB) that consists of a multilayered, box-shaped core embedded in an amorphous
      corona from which the microtubules emerge. The composition of the NAB is still
      largely unresolved. Here we have examined a high molecular mass component of the
      NAB which was identified by a monoclonal antibody raised against isolated
      nucleus/NAB complexes. This antibody recognized a 350 kDa component which is
      immunologically related to the D. discoideum heavy chain of myosin II. The 350
      kDa antigen was localized only at the NAB in interphase cells, while in mitotic
      cells it may also be found in the vicinity of the NAB as well as in association
      with the mitotic spindle. Immunogold labeling experiments showed that the protein
      is part of the NAB corona. This association was not destroyed by treatment with 2
      M urea or 0.6 M KCl. The 350 kDa antigen was part of the thiabendazole-induced
      cytoplasmic microtubule-organizing centers. A direct role in the polymerization
      of tubulin could not be determined in an in vitro microtubule nucleation assay,
      whereas antibody electroporation of live cells appeared to interfere with the
      generation of a normal microtubule system in a subset of cells. Our observations
      suggest that the 350 kDa antigen is a structural component of the NAB corona
      which could be involved in its stabilization.

PMID- 9004046
TI  - Cleavage and inactivation of DNA-dependent protein kinase catalytic subunit
      during apoptosis in Xenopus egg extracts.
AB  - DNA-dependent protein kinase (DNA-PK) consists of a 460 kDa subunit that contains
      the catalytic domain (DNA-PKcs) complexed with two polypeptides of 70 kDa and 80
      kDa (Ku70 and Ku80) which comprise the Ku autoantigen. DNA-PKcs requires
      association with DNA via Ku for catalytic activation and is implicated in double
      strand break repair, V(D)J recombination and transcription. We have utilised a
      cell-free system of concentrated Xenopus laevis egg extracts to investigate the
      regulation and possible functions of DNA-PK. Recently, we have shown that this
      system can reproduce events of apoptosis, including activation of an apoptotic
      protease that cleaves poly(ADP-ribose) polymerase. Here, we report that DNA-PK is
      rapidly inactivated with the onset of apoptosis in this system. Loss of activity
      is concomitant with cleavage of the catalytic subunit, whereas the Ku subunits
      are stable. Cleavage and inactivation of DNA-PKcs is prevented by prior addition
      of the anti-apoptotic protein Bcl-2 or inhibition of an apoptotic protease that
      has characteristics of the CPP-32/Ced-3 family of cysteine proteases that cleave
      poly(ADP-ribose) polymerase. These results suggest that cleavage and inactivation
      of DNA-PKcs prevents this factor from functioning in DNA repair, recombination or
      transcriptional regulation during apoptosis.

PMID- 9004049
TI  - Newer antidepressants: hypotheses and evidence.

PMID- 9004047
TI  - A family of glycoproteins (GP55), which inhibit neurite outgrowth, are members of
      the Ig superfamily and are related to OBCAM, neurotrimin, LAMP and CEPU-1.
AB  - We have previously identified a glycosylphosphatidylinositol-linked glycoprotein
      of 55 kDa (GP55) which inhibits neurite outgrowth. We now provide evidence that
      GP55, isolated from adult chick brain, consists of at least two bands, both of
      which are active, i.e., block outgrowth of neurites from chick dorsal root
      ganglion neurons. An antiserum raised against the adult proteins reverses the
      inhibition and preliminary experiments suggest that GP55 is restricted to the
      nervous system, increases during development from very low levels at embryonic
      day 10 and is most abundant after hatching. Immunofluorescence reveals that GP55
      is expressed on neurons cultured from an embryonic day 14 chick brain but is
      barely detectable on embryonic day 10 dorsal root ganglion neurons or embryonic
      day 8 forebrain neurons; the neurons which respond to substrate-bound GP55.
      Peptide sequencing revealed considerable homology with OBCAM, a protein
      previously identified on the basis of binding opiates. Nested polymerase chain
      reaction using primers to the OBCAM sequence and internal primers to GP55
      peptides produced two different polymerase chain reaction fragments with homology
      to OBCAM. A full length clone (E19S) corresponding to one polymerase chain
      reaction product and a partial length clone (E14S) corresponding to the second
      have been isolated from an embryonic chick brain library. Both are members of the
      immunoglobulin superfamily and have (or are expected to have) three C2 domains.
      E19S has 90% homology with LAMP at the amino acid level. This sequence only
      partially matches the peptides from the adult protein and hence is probably not a
      major component of the adult proteins. E14S (GP55-A) has 83% homology to OBCAM at
      the amino acid level over the region sequenced. The sequence matches several of
      the peptides from the adult protein and is hence likely to correspond to a major
      component of the adult proteins. Thus members of the GP55 family are related to
      OBCAM, neurotrimin, LAMP and a recently discovered chick protein CEPU-1. Our
      results suggest molecules within this family are capable of acting as cell
      adhesion molecules and inhibitors of neurite outgrowth.

PMID- 9004048
TI  - Laminins promote the locomotion of skeletal myoblasts via the alpha 7 integrin
      receptor.
AB  - The alpha 7 beta 1 integrin is specifically expressed by skeletal and cardiac
      muscles, and its expression and alternative mRNA splicing at the cytoplasmic
      domain are developmentally regulated. We analyzed the role of alpha 7 integrin in
      mediating myoblast adhesion and motility on different laminin isoforms. Mouse
      C2C12 and MM14 myoblast cell lines were found by flow cytometry and
      immunoprecipitation to express high levels of the alpha 7 integrin. Overall
      expression of alpha 7 increased as the C2C12 myoblasts differentiated; myoblasts
      expressed only the alpha 7B cytoplasmic variant whereas in differentiating
      myotubes alpha 7A increased markedly. Function-perturbing monoclonal antibodies
      generated to alpha 7 integrin efficiently blocked both adhesion and migration of
      MM14 and C2C12 mouse myoblasts on laminin 1. Other studies with MM14 myoblasts
      showed that alpha 7 is also a receptor for laminin 2/4 (human placental merosins)
      but not for epithelial-cell-specific laminin 5. Blocking antibody to alpha 7 only
      partially inhibited adhesion to laminin 2/4 but almost completely blocked
      motility on this substrate. Finally, to assess the potential role of the alpha 7
      cytoplasmic domain, CHO cells were stably transfected to expressed chimeric alpha
      5 cDNA constructs containing the wild-type alpha 5 or the alpha 7A or alpha 7B
      cytoplasmic domain; all forms of the integrin showed identical activities for
      adhesion, migration, proliferation, and matrix assembly on fibronectin
      substrates. These results established that alpha 7 beta 1 receptor can promote
      myoblast adhesion and motility on a restricted number of laminin isoforms and may
      be important in myogenic precursor recruitment during regeneration and
      differentiation.

PMID- 9004050
TI  - Long-term pharmacotherapy of obsessive-compulsive disorder: a double-blind
      controlled study.
AB  - The aim of this study was to investigate whether obsessive-compulsive patients
      previously treated successfully with clomipramine or fluvoxamine could tolerate
      reduction of the daily dosage without worsening of the clinical condition. Thirty
      informed obsessive-compulsive patients, given a diagnosis according to DSM-III-R
      criteria, were recruited consecutively into the study. Patients were blindly
      assigned to one of the groups of treatment with different rates of reduction of
      the previously effective daily drug dosage: group 1 (control group, no
      reduction), group 2 (reduction of 33-40%), and group 3 (reduction of 60-66%). The
      entire study lasted 102 days. From baseline to the end of the study, the clinical
      condition was evaluated by the administration of standardized tests (Yale-Brown
      Obsessive-Compulsive Scale, Hamilton Rating Scale for Depression, Clinical Global
      Impression [CGI] scale), and blood samples were collected for plasma drug level
      determinations. The criterion for discontinuation of the study was the worsening
      of obsessive-compulsive symptoms, arbitrarily defined by an increase of > 5% from
      the baseline total Yale-Brown Obsessive-Compulsive Scale score, as measured in
      two successive assessments, and a worsening of global clinical condition as
      measured by the CGI scale. The main result of the study was borne out from the
      survival analysis. There were no significant differences in the cumulative
      proportion of patients from each group of treatment who did not worsen during the
      102 days of observation. This preliminary result, which needs to be confirmed in
      larger samples, suggests that long-term maintenance therapy for obsessive
      compulsive disorder might be provided with lower dosages of the antiobsessional
      drug, with clear advantages for tolerability and compliance.

PMID- 9004051
TI  - Correlated reductions in cerebrospinal fluid 5-HIAA and MHPG concentrations after
      treatment with selective serotonin reuptake inhibitors.
AB  - We sought to determine whether fluvoxamine and fluoxetine, two different
      antidepressants with in vitro selectivity for the serotonin uptake transporter
      also demonstrated similar selectivity in vivo. To accomplish this, we measured
      cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA),
      3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) before and
      after 6 weeks of treatment with these two drugs. Twenty-four subjects who had
      major depression according to DSM-III-R criteria gave written, informed consent
      for the collection of CSF during a double-blind comparative treatment trial of
      fluvoxamine (50-150 mg/day) and fluoxetine (20-80 mg/day). The symptoms of
      subjects were assessed clinically on a weekly basis throughout the treatment
      trial. CSF samples were obtained after a 7- to 14-day washout period before
      treatment and again at the end of treatment. CSF samples were analyzed for 5
      HIAA, HVA, and MHPG using high-pressure liquid chromatography coupled to
      electrochemical detection. Fluvoxamine- and fluoxetine-treated patients did not
      differ in clinical outcome or in the CSF concentrations of monoamine metabolite
      levels before or after treatment. Therefore, the CSF data were pooled. Drug
      treatment, overall, was associated with significant decreases in 5-HIAA and MHPG
      and a trend toward a reduction in HVA levels. Levels of 5-HIAA, MHPG, and HVA
      were reduced by 57%, 48%, and 17%, respectively. In addition, the magnitude of
      the decreases in 5-HIAA and MHPG appeared to be correlated (r = 0.83) across the
      subjects, although a Spearman rank correlation indicated that outlying values had
      an undue effect on this relationship. These results suggest that treatment with
      selective serotonin reuptake inhibitors, which are selective for serotonin uptake
      in vitro, does not show a similarly selective effect on serotonin in vivo during
      treatment of patients.

PMID- 9004052
TI  - Electrocardiographic effects of fluoxetine and doxepin in patients with major
      depressive disorder.
AB  - Cardiovascular adverse effects are amongst the most serious observed with
      antidepressant drugs and are often due to effects on cardiac conduction and
      refractoriness. However, such electrophysiologic effects may not be evident when
      using conventional electrocardiographic measures. Forty patients with major
      depressive disorder (according to DSM-III-R criteria) were enrolled in a 6-week
      double-blind parallel group study of fluoxetine (N = 20) or doxepin (N = 20).
      Cardiac conduction (QRS duration) and repolarization (corrected QT interval,
      QTc), were measured using signal-averaged electrocardiograms and 12-lead
      electrocardiogram at baseline and after 2, 4, and 6 weeks of treatment. Patients
      taking doxepin (mean daily dosage at 6 weeks 169 +/- 42 mg) were similar to those
      taking fluoxetine (37 +/- 18 mg) for demographic variables and improvement in
      depression scores but volunteered more side effects (p = 0.011), especially dry
      mouth (p < 0.001) and dizziness/lightheadedness (p = 0.005). After 6 weeks,
      doxepin increased heart rate (69 +/- 12 to 81 +/- 13 beats per minute; p =
      0.0003) and prolonged QTc (from 417 +/- 36 to 439 +/- 28 msec; p < 0.03); overall
      QRS duration was not prolonged but was correlated with serum doxepin
      concentrations (r = 0.78, p < 0.0001). Fluoxetine had no effect on QTc (428 +/-
      24 msec at baseline vs. 430 +/- 24 msec at 6 weeks) or QRS duration (97 +/- 12
      msec at baseline vs. 94 +/- 12 msec at 6 weeks). The standard 12-lead
      electrocardiogram showed no significant change in QRS or QTc for either drug.
      Using a sensitive measure of electrocardiographic effects, doxepin prolongs
      repolarization and may slow cardiac conduction. Fluoxetine has no measurable
      electrocardiographic effects, which suggests an increased safety margin for
      cardiac adverse effects. The ability of the signal-averaged electrocardiogram to
      resolve small changes in the electrocardiogram is useful in the assessment of
      drugs with subtle electrophysiologic effects.

PMID- 9004053
TI  - Gradual discontinuation of lithium augmentation in elderly patients with unipolar
      depression.
AB  - Recently, the therapeutic benefit of lithium augmentation in old age has come
      into question. These data, in light of the documented high incidence of side
      effects after lithium use in elderly patients, resulted in the design of a
      prospective, placebo-controlled lithium augmentation withdrawal study in elderly
      patients with unipolar depression. Twelve eligible geriatric patients (10 women
      and 2 men; mean [+/-SD] age, 76.2 +/- 5.7 years) with DSM-III-R unipolar
      depression receiving adjunct lithium therapy were randomized to receive continued
      lithium augmentation or matching placebo (withdrawal rate 150 mg/day/wk). At each
      clinic visit, patients were assessed for depression (Montgomery-Asberg Depression
      Rating Scale and Geriatric Depression Rating Scale) and lithium-induced
      toxicities (a 21-item side-effect checklist, renal and thyroid biochemistry).
      Over the 2-year observation period, the placebo group reported a decrease in
      composite 21-item side-effect score and specific lithium toxicities (e.g.,
      urinary urgency, hand tremor, and renal/thyroid abnormalities). Two patients in
      the lithium maintenance group had a recurrence of depression at 61 and 96 weeks,
      respectively, immediately after a stressful life event (cerebrovascular accident
      [CVA] or death of spouse), and two patients had a recurrence in the placebo group
      at 7 and 92 weeks, respectively, without any apparent changes in life stresses.
      No other prognostic risk factors for recurrence were identified. Depression that
      recurred in patients who were receiving placebo was relatively resistant to
      reinstitution of lithium augmentation therapy. In otherwise stable geriatric
      patients with unipolar depression, the documented benefits of reduced side
      effects should be weighed against the risk of recurrence and subsequent lithium
      resistance before withdrawal of lithium augmentation.

PMID- 9004054
TI  - The effect of nefazodone on the single-dose pharmacokinetics of phenytoin in
      healthy male subjects.
AB  - The effect of nefazodone on the pharmacokinetics of a single dose of phenytoin
      was evaluated in 18 healthy male subjects. The subjects received a single oral
      dose of phenytoin, 300 mg, on day 1 of the study and the pharmacokinetic profile
      of the drug was determined. After a washout period followed by oral
      administration of nefazodone, 200 mg twice daily for 7 days, subjects received a
      single dose of phenytoin, 300 mg concomitantly with the morning dose of
      nefazodone on day 12, and the pharmacokinetic profile of phenytoin was determined
      again. Minimum plasma concentrations of nefazodone and its main metabolites
      indicated that steady state had been achieved for nefazodone when phenytoin and
      nefazodone were administered concomitantly. No significant differences were
      demonstrated between mean single-dose pharmacokinetic parameters of phenytoin
      when administered alone on day 1 and concomitantly with nefazodone on day 12.
      Assessment of adverse events, clinical laboratory parameters, electrocardiograms,
      vital signs, and physical examinations indicated that concomitant administration
      of nefazodone and phenytoin was safe and well tolerated. These data demonstrate
      that nefazodone does not affect the single-dose pharmacokinetics of phenytoin,
      but do not preclude the possibility of such an interaction when phenytoin is
      administered on a long-term basis. A clinically significant interaction between
      nefazodone and phenytoin through a pharmacokinetic mechanism is unlikely.

PMID- 9004055
TI  - Methamphetamine psychosis: spontaneous recurrence of paranoid-hallucinatory
      states and monoamine neurotransmitter function.
AB  - We studied the process that triggers spontaneous recurrences of methamphetamine
      (MAP) psychosis, a phenomenon known as flashbacks, in 28 female patients who
      experienced flashbacks, by comparing them with 92 female nonflashbackers with a
      history of previous MAP psychosis. The study evaluated plasma monoamine
      neurotransmitter function in 12 of the 28 flashbackers and in 8 of the 92
      nonflashbackers. Control data were obtained from 28 normal, healthy females
      composed of 13 MAP users and 15 nonusers, none of whom became psychotic. The 28
      flashbackers had experienced significantly greater frequencies of threatening
      events and frightening paranoid-hallucinatory states during previous MAP abuse
      than the 92 nonflashbackers. The dominant triggering factor was a mild fear of
      other persons. Plasma norepinephrine (NE) levels were significantly higher in the
      12 flashbackers during flashbacks than during periods of normalcy and were
      significantly higher than those in the 13 user and 15 nonuser control subjects.
      Plasma NE levels in the 12 flashbackers during periods of normalcy were
      significantly higher than those in the 13 user control subjects. The eight
      nonflashbackers had significantly higher NE levels than the 13 user control
      subjects. This suggests that an increase in peripheral noradrenergic activity may
      be related to the occurrence of flashbacks. The present study suggests that
      repeated MAP use with frightening experiences may induce sensitivity to
      psychosocial stressors. A mild fear of other persons may have actualized the
      encoded frightening memories associated with the frightening experiences via
      increased sensitivity to psychosocial stressors. Thus, flashbacks may have been
      caused through an increase in peripheral noradrenergic activity.

PMID- 9004056
TI  - Concurrent treatment of nonresistant major depression with desipramine and
      lithium: a double-blind, placebo-controlled study.
AB  - The objective of this study was to compare the onset, rate of antidepressant (AD)
      response, and treatment outcome of depressed patients treated for 5 weeks with
      either the concomitant administration of the tricyclic AD desipramine (DMI) and
      lithium carbonate (Li) or with DMI alone. In this double-blind, placebo
      controlled study, 31 nonpsychotic, mild to moderately depressed outpatients (DSM
      III-R unipolar or bipolar major depression) were randomly assigned to 5 weeks of
      treatment with DMI plus Li (N = 16) or DMI plus placebo (N = 15). Drug dosages
      were adjusted to achieve therapeutic plasma levels. Clinical state was rated
      weekly by the Hamilton Rating Scale for Depression, the Clinical Global
      Impression Scale, a Visual Analogue Self-Report Scale, and an adverse-effect
      form. Twenty-seven patients completed the study, 12 in the DMI-Li group and 15 in
      the DMI-placebo group. Four patients dropped out due to adverse events, all from
      the DMI-Li group. Both groups responded well to treatment, without a significant
      difference between them in the rate of response of final outcome. Sixty-seven
      percent (10/15) of the patients taking DMI only and 75% (9/12) of the patients
      taking DMI plus Li met our response criteria. The combination of DMI and Li was
      associated with significantly more adverse effects than DMI alone. Concurrent
      treatment with Li did not demonstrate an enhancement of either DMI's efficacy or
      its onset of action in these patients, suggesting that this strategy may not
      confer any additional benefit compared with DMI alone in mild to moderately
      depressed patients who are not preselected for nonresponse to an AD during their
      current depressive episode.

PMID- 9004058
TI  - Doxycycline-induced lithium toxicity.

PMID- 9004057
TI  - The effects of clozapine on symptom clusters in treatment-refractory patients.
AB  - Preliminary results of a double-blind clozapine study in a population of chronic
      psychotic patients at a state psychiatric facility are reported. Thirty
      "treatment-refractory" schizophrenic patients given a diagnosis according to DSM
      III-R criteria (mean age of 44 +/- 9.1 years and a duration of illness of 24.9 +/
      8.8 years) who received 300 mg or 600 mg of clozapine and randomized in a double
      blind fashion were analyzed. Subjects were evaluated using the Brief Psychiatric
      Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale on a weekly
      basis for 16 weeks. Based on the changes in their CGI scores at week 16 of
      clozapine treatment, subjects were retrospectively categorized as "improvers" (N
      = 12) and "nonimprovers" (N = 18). The two groups were compared for changes in
      total BPRS and BPRS factor scores. In terms of total BPRS scores, we expected a
      difference between the two groups because they were categorized based on changes
      in their CGI scores. However, the total BPRS scores in improvers showed a
      significant decrease by week 6 of clozapine treatment. On analyzing the four BPRS
      factors, the improvers showed improvement in the thinking disturbance factor by
      week 1 that remained steady from week 7. On the hostility-suspiciousness factor,
      the improvers showed an improvement across time when compared with nonimprovers.
      The withdrawal-retardation factor showed improvement in both groups across time,
      whereas the anxiety-depression factor was least influenced by clozapine. These
      observations suggested that all BPRS symptom factors did not uniformly contribute
      to improvement in overall psychopathology, which was observed as a decrease in
      total BPRS scores.

PMID- 9004059
TI  - Transient aphasia associated with lithium intoxication.

PMID- 9004060
TI  - Social phobia-related nausea relieved with adjunctive cisapride.

PMID- 9004061
TI  - Induction of mania by risperidone resistant to mood stabilizers.

PMID- 9004062
TI  - A case report of risperidone-induced obsessive-compulsive symptoms.

PMID- 9004063
TI  - Gabapentin for behavioral agitation in Alzheimer's disease.

PMID- 9004064
TI  - Withdrawal hypomania associated with paroxetine.

PMID- 9004066
TI  - Fluoxetine and suicidal ideation.

PMID- 9004065
TI  - Patient prescribed sertraline charged with driving under the influence.

PMID- 9004067
TI  - Grapefruit juice and clomipramine: shifting metabolitic ratios.

PMID- 9004068
TI  - Dystonia associated with trazodone and sertraline.

PMID- 9004070
TI  - Venlafaxine, monoamine oxidase inhibitors, and the serotonin syndrome.

PMID- 9004069
TI  - A case of neuroleptic malignant syndrome and serotonin disturbance.

PMID- 9004071
TI  - Sexual dysfunction associated with serotonin specific reuptake inhibitors.

PMID- 9004073
TI  - Marked liver enzyme elevations with clozapine.

PMID- 9004072
TI  - Worsening of psychosis with clozapine and selective serotonin reuptake inhibitor
      combination: two case reports.

PMID- 9004074
TI  - Unsuccessful reexposure to clozapine.

PMID- 9004075
TI  - Expression of major histocompatibility complex class II molecules by dermal
      inflammatory cells, epidermal Langerhans cells and keratinocytes in canine
      dermatological disease.
AB  - The distribution of Major Histocompatibility Complex (MHC) Class II molecules in
      skin biopsies from 42 dogs with primary skin disease and six control dogs was
      examined by indirect immunohistochemical methods. Canine epidermal Langerhans
      cells constitutively expressed MHC Class II and the number of such cells was
      increased in the epidermis of dogs with discoid lupus erythematosus (n = 10),
      hypersensitivity dermatitis (n = 10) or deep pyoderma (n = 13) but not in eight
      cases of pemphigus foliaceus. Expression of MHC Class II by epidermal and
      follicular keratinocytes was observed in a ninth dog with pemphigus foliaceus.
      Within dermal inflammatory infiltrates, Class II was expressed by macrophages,
      dendritic cells and fibroblasts but not by neutrophils, eosinophils, mast cells
      or plasma cells. Only occasional dermal lymphocytes expressed surface MHC Class
      II, but nodular aggregates of strongly Class II-positive lymphocytes were
      observed within the dermis of two dogs with discoid lupus erythematosus.

PMID- 9004076
TI  - Subcellular changes in platelets in acute and subacute African swine fever.
AB  - The morphological changes in platelets in acute and subacute African swine fever
      (ASF) and their relationship to pathogenesis were studied. Eight pigs were
      inoculated with a highly virulent strain of African swine fever (Malawi '83) and
      14 with a moderately virulent strain (Dominican Republic '78) for ultrastructural
      study of platelets, monocyte/macrophages and vascular structures in the liver,
      spleen, lymph node, bone marrow, lung and kidney. Both viruses produced
      activation and degranulation of platelets from day 3 after inoculation onwards,
      coinciding with activation of the mononuclear phagocyte system and virus
      replication in monocyte/macrophages. Platelet aggregation and viscous
      metamorphosis of platelets were observed at 5 and 7 days after inoculation with
      the highly virulent strain, coinciding with endothelial alterations, but platelet
      aggregation was less prevalent and there was no sign of viscous metamorphosis in
      animals inoculated with the moderately virulent strain. Virions within platelets
      were observed at the final stage of acute ASF and at 5-7 days after inoculation
      in subacute ASF. This suggests that platelets assist in disseminating ASF virus
      within the body, especially in subacute infections.

PMID- 9004077
TI  - Changes in the distribution of cells expressing tumour-associated antigen in
      lymph nodes during the progression of enzootic bovine leukosis.
AB  - A monoclonal antibody (MAb), c143, that recognizes a tumour-associated antigen
      that is "upregulated" on neoplastic B cells in cattle with enzootic bovine
      leukosis (EBL), was used as a marker to study disease progression. An
      immunohistochemical examination of neoplastic tissue and superficial cervical
      lymph nodes from 14 animals with EBL revealed three morphologically definable
      stages of change in the structure of lymph nodes, associated with the
      distribution of c143-positive cells: (1) the presence of c143-positive cells at
      the marginal sinus with no apparent changes in lymph node structure; (2) the
      presence of positive cells extending into and distorting the architecture of the
      lymph node, with clear evidence of proliferation before overt changes
      (enlargement of lymph nodes) were evident; and (3) the presence of positive cells
      throughout the lymph node with total disruption of lymph node structure when
      clinical signs of lymph node enlargement were evident. The results indicated that
      the bovine leukaemia virus-transformed lymphocytes or neoplastic cells in
      peripheral blood accumulate in the marginal sinus area at the earliest stages,
      and subsequently proliferate and infiltrate into follicles, leading to the
      development of clinical signs of lymphosarcoma.

PMID- 9004078
TI  - Cycloheximide-induced apoptosis in melanoma cells derived from regressing
      cutaneous tumours of Sinclair swine.
AB  - The role of apoptosis in the spontaneous regression of Sinclair swine melanoma
      was investigated in vitro with swine melanoma cell lines. Growth characteristics
      and sensitivity to cycloheximide-induced apoptosis were determined in melanoma
      cell lines derived from tumours that were progressing or undergoing regression in
      vivo. In contrast to cell lines derived from progressing tumours, those derived
      from regressing tumours showed induction of apoptosis; this phenomenon was
      dependent on dose but independent of cell growth stage in culture. Chromatin
      condensation, cell shrinkage, and fragmentation into apoptotic bodies, as well as
      DNA fragmentation into large kilobase fragments, occurred in cell lines from
      regressing tumours but not from progressing tumours. These findings suggest that
      swine melanoma cells are inherently more sensitive to cell death during tumour
      regression. The apoptosis-sensitive and resistant cell lines will be important
      for further studies of the roles of cell signalling pathways and gene expression
      in tumour regression.

PMID- 9004079
TI  - Interferon-gamma mediates long-term persistent Chlamydia psittaci infection in
      vitro.
AB  - The long-term anti-chlamydial effects of recombinant ovine interferon gamma
      (rOvIFN-gamma) were studied in ovine ST-6 fibroblasts infected with the S26/3
      strain of Chlamydia psittaci. Chlamydial multiplication was assessed by enzyme
      linked immunosorbent assay analysis of supernate lipopolysaccharide, titration of
      inclusion-forming units in culture supernates, and enumeration of inclusion
      bodies in cultured cells at 7-day intervals. Concentrations of 250 and 1000 U/ml
      of rOvIFN-gamma resulted in a microbistatic inhibition of C. psittaci growth,
      which appeared to become microbicidal when rOvIFN-gamma was maintained in the
      cultures for 14 days or more. There were no signs of C. psittaci multiplication
      when cultures were maintained in 25 or 100 U/ml of rOvIFN-gamma. However,
      subsequent removal of rOvIFN-gamma from these cultures resulted in a re-emergence
      of viable, infectious chlamydiae, which eventually killed all the fibroblasts.
      This re-emergence was more rapid in cultures initially treated with 25 U/ml of
      rOvIFN-gamma than in those treated with 100 U/ml.

PMID- 9004080
TI  - Replication of equid herpesvirus-1 (EHV-1) in the testes and epididymides of
      ponies and venereal shedding of infectious virus.
AB  - Six Welsh Mountain pony colts were infected intranasally with the Ab4 isolate of
      EHV-1. Clinical and virological monitoring demonstrated mild upper respiratory
      tract disease, with nasal shedding of virus and establishment of a cell
      associated viraemia. Detailed pathological examination of the urogenital tract
      was performed post mortem on days 4-9 post-infection (PI). EHV-1 was isolated
      from the epididymis on day 8 and the testis on day 9 PI, with viral replication
      in endothelial cells of these organs and an associated necrotizing vasculitis and
      thrombosis. Productive viral infection of germinal epithelium was not observed.
      In a further study, three Welsh Mountain pony stallions were infected
      intranasally with Ab4, which again resulted in mild upper respiratory tract
      disease and the establishment of a cell-associated viraemia. Semen samples were
      collected up to day 60 PI. Two stallions showed a decrease in the proportion of
      morphologically normal sperm. Significant numbers of inflammatory cells were
      observed in the sperm-rich fraction of ejaculates collected from one stallion
      between days 16 and 28 PI; infectious virus was recovered from the semen of this
      animal between days 17 and 25 PI, after the cessation of viraemia. The affected
      stallion appeared clinically normal over the period of venereal EHV-1 shedding.

PMID- 9004081
TI  - Expression of stem cell factor receptor (c-kit) by the malignant mast cells from
      spontaneous canine mast cell tumours.
AB  - Stem cell factor receptor (SCFR, c-kit), normally expressed on haematopoietic and
      mast cells, plays a regulatory role in cellular growth and differentiation.
      Dysregulated expression of SCFR may contribute to neoplastic transformation. We
      investigated expression of SCFR on malignant canine mast cells obtained directly
      from spontaneous canine mast cell neoplasms, in an attempt to determine whether
      these undifferentiated cells maintained expression of this growth-promoting
      cytokine receptor. Malignant mast cells (histological grade 2) from skin tumours
      or lymph node metastases were collected from canine patients, and SCFRs were
      detected by flow cytometric analysis of these cells. All of the tumours bound
      mouse and canine recombinant stem cell factor (SCF), indicating that the cells
      not only expressed SCFRs, but that the receptors possessed the functional
      property of ligand binding. Immunoglobulin Fc receptors for canine IgE were
      identified on these cells by flow cytometry, a further indication that the cells
      analysed were mast cells and retained some differentiated features.
      Immunohistochemical analysis of formalin-fixed, paraffin wax-embedded mast cell
      tumour biopsies confirmed expression of SCFRs by malignant cells from each
      tumour. The relative binding of SCF to suspensions of tumour cells, as assessed
      by flow cytometry, correlated with the intensity of immunolabelling for SCFR in
      sections of the same tumours, suggesting variability in SCFR expression between
      tumours. Agarose gel electrophoresis of the products of SCFR reverse
      transcription-polymerase chain reaction derived from each tumour had the
      molecular weight predicted for canine SCFR cDNA on the basis of the mouse and
      human counterparts. This further confirmed SCFR expression by malignant canine
      mast cells. Taken together, these results show that a membrane receptor capable
      of triggering cell growth is expressed by malignant canine mast cells, suggesting
      a role for this receptor in the aetiology of canine mast cell cancer. This
      relatively common malignancy of the dog would seem to present an opportunity for
      the investigation of the potential role of the SCF/SCFR pathway in the
      development of spontaneous malignancies of mast cells.

PMID- 9004082
TI  - Apoptosis in lymph nodes in acute African swine fever.
AB  - This paper reports apoptosis of lymph-node lymphocytes in swine experimentally
      inoculated with a virulent African swine fever (ASF) virus isolate (Malawi '83).
      Apoptosis was observed in both compartments of cortical tissue, but was more
      intense in diffuse lymphoid tissue (T area). Lymphopenia detected in peripheral
      blood was associated with T-lymphocyte depletion. No evidence of ASF virus
      replication was observed in lymphocytes in the lymph nodes studied. This finding,
      together with the high rate of virus replication recorded in macrophages in
      diffuse lymphoid tissue as compared with the low rate recorded for lymphoid
      follicles, suggests a mechanism for the induction of apoptosis related to virus
      replication in cells of the mononuclear phagocyte system.

PMID- 9004083
TI  - Leucocyte and endothelial cell adhesion molecule expression in porcine
      histiocytic leiomyofibrosarcoma.
AB  - A histiocytic sarcoma was present at birth in a pig. On the basis of ultra
      structure and structural-protein composition (presence of alpha-smooth-muscle
      actin but not keratin), the sarcoma component was identified as a
      leiomyofibrosarcoma. Lipid-laden macrophages (histiocytes), which permeated the
      tumour in an apparently random fashion, were somewhat atypical in that they were
      negative for some macrophage markers; they gave a reaction, however, for CDw14.
      Despite its aggressive metastatic capacity, this tumour occurred almost
      exclusively in the subcutis, dermis and skeletal muscle. The tumour was
      extensively vascularized with many small capillaries which did not express E
      selectin (CD69E), MHC class II or the L-selectin (CD69L) ligand, markers
      characteristic of inflamed (activated) endothelial cells in pig skin. Significant
      numbers of the histiocytes were positive for the integrins CD18 and VLA-4
      (CD49d), indicating involvement of integrin pathways in the spread or growth, or
      both, of the leiomyofibrosarcoma. Most of the fibrous sarcoma cells also had
      extensive reactivity with an antibody to the standard variant form of CD44
      (CD44s).

PMID- 9004085
TI  - Transgenics and essential hypertension.
AB  - Primary or "essential' hypertension is generally perceived to be a multifactorial
      or complex genetic trait. An individual's susceptibility to high blood pressure
      (BP) is influenced not only by the many genetic factors, which effect control
      through biochemical and physiological mechanisms, but also by environmental
      determinants. In a small proportion of human hypertensives the cause is a single
      genetic defect, exhibiting Mendelian characteristics. The vast heterogeneous
      majority, however, result from a multitude of contributing factors, making
      identification of the underlying etiology very difficult. We will briefly review
      a number of strategies which have helped to identify genetic factors involved in
      hypertension. These include the search for genetic defects in Mendelian forms of
      hypertension, intensive study of classical animal models such as the
      spontaneously hypertensive rat, and linkage analyses in animal models and
      hypertensive patients. We will then discuss the role which transgenesis can play
      in complementing and extending such analyses.

PMID- 9004084
TI  - Development of morphological changes and ileal glucagon gene expression in the
      small intestine of lambs infected with Trichostrongylus colubriformis.
AB  - To investigate the consequences of subclinical Trichostrongylus colubriformis
      infection on the intestinal mucosa and the associated changes in entero-glucagon
      gene expression, sheep were infected with 30000 larvae and killed 5, 10, 15 or 20
      days after infection. Histological and cytological changes were examined. In the
      main site of infection, the upper duodenum, villous atrophy associated with crypt
      hyperplasia developed gradually. Cytological changes in the enterocytes appeared
      concurrently, characterized by a progressive reduction in brush border and in the
      number of ribosomes in the cytoplasm, changes in the internal structure of
      mitochondria, and enlargement of the intercellular spaces. Neither histological
      nor cytological modifications were found before day 15. At the same time, villous
      hypertrophy developed distally, beyond the main site of infection; this was
      interpreted as an adaptive response to parasitism. Enteroglucagon gene expression
      in the ileum was measured in parallel with the mucosal changes but did not reveal
      any difference between infected and control sheep. The results indicate that this
      gastrointestinal hormone does not have a major role in the response to nematode
      parasitism.

PMID- 9004086
TI  - Central role of the kidney and abnormal fluid volume control in hypertension.
AB  - In human essential hypertension, and in all forms of experimental hypertension
      studied thus far, volume regulation and the relationship between blood pressure
      (BP) and sodium excretion (pressure natriuresis) are abnormal. Considerable
      evidence indicates that resetting of pressure natriuresis plays a key role in
      causing hypertension, rather than merely occurring as a consequence of increased
      BP. In patients with essential hypertension, resetting of pressure natriuresis is
      characterized either by a parallel shift to higher BPs and salt-insensitive
      hypertension, or by a decreased slope of pressure natriuresis and salt-sensitive
      hypertension. This clearly indicates that essential hypertension cannot be
      ascribed to a single abnormality of kidney function. Multiple physiological
      studies have shown that salt-sensitive hypertension can be elicited by renal
      abnormalities that cause either loss of functional kidney mass or an inability to
      modulate the renin-angiotensin-aldosterone (RAA) system appropriately; these
      abnormalities include loss of functional nephrons, decreased glomerular capillary
      filtration coefficient, patchy renal ischemia, and increased distal and
      collecting tubular reabsorption. Renal abnormalities that cause salt-insensitive
      hypertension are characterized by normal functional kidney mass, and the ability
      to appropriately modulate the renin-angiotensin system during changes in sodium
      intake; important causes of salt-insensitive hypertension include widespread
      increases in preglomerular resistance and increased reabsorption in the proximal
      tubules and loops of Henle. By comparing the characteristics of pressure
      natriuresis in essential hypertensive subjects with those found in experimental
      hypertension of known origin, we can gain considerable insight into the etiology
      of human hypertension.

PMID- 9004087
TI  - The importance of the kidney in primary hypertension: insights from cross
      transplantation.
AB  - Experimental renal cross-transplantation studies with genetically hypertensive
      and normotensive rats have shown that hypertension travels with the kidney. The
      underlying mechanisms are currently not well understood. Genetically normotensive
      recipients of a kidney from spontaneously hypertensive rats show a decreased
      capacity to excrete sodium when challenged with a high-salt diet. Furthermore,
      they retain more sodium than recipients of a kidney from genetically normotensive
      donors immediately after transplantation and removal of the native kidneys.
      Sodium retention precedes hypertension and may contribute to its development.
      Most recently, it has been shown that bilateral nephrectomy and transplantation
      of a genetically normotensive kidney attenuates the development of hypertension
      in young transplanted spontaneously hypertensive rats. Thus, long-term blood
      pressure in renal transplanted rats is critically determined by the genetic
      background of the renal graft. Together, these data indicate that genetically
      determined renal mechanisms play a major role in primary hypertension.

PMID- 9004088
TI  - Sodium and the kidney in essential hypertension.
AB  - Several primary renal abnormalities are implicated in the pathogenesis of
      hereditary hypertension which are potentially capable of impairing sodium
      excretion. It is proposed that their diversity and number, and the particular
      combination present, are responsible for the hypertension and its heterogeneity.

PMID- 9004089
TI  - Genetic determinants and renal mechanisms in essential hypertension.
AB  - Human essential hypertension is a polygenic disease whose phenotypic expression
      is modulated by the environment. Though the kidney could play a major role in the
      initiation and maintainment of hypertension, many questions remain open. Rat
      models of primary hypertension provided the substantial information with
      experiments on kidney cross-transplantation, showing that at least a portion of
      hypertension could be transplanted with the kidney in all strains where such an
      experiment has been carried out. Data consistent with those of rats have also
      been obtained in humans. Many abnormalities in kidney function and cell membrane
      ion transport have been described in hypertensive rats and humans, but the
      logical sequence of events from a genetic-molecular abnormality to a cellular
      abnormality which causes hypertension via a modification of kidney function is
      difficult to prove. We established this sequence in Milan hypertensive rats using
      a variety of experimental techniques such as the study of isolated kidney and
      renal cell function, cell membrane ion transport, cross-immunisation with
      membrane proteins, molecular biology, genetic crosses and manipulation. Such
      study led to the identification of a polymorphism in the cytoskeletal protein
      adducin. Recently, alpha-adducin variants have been associated to both primary
      hypertension and salt sensitive hypertension. Finally, recent findings strongly
      support the hypothesis that adducin variants may affect kidney function by
      modulating the overall capacity of the tubular epithelial cells to transport ions
      through both a modification in the assembly of actin cytoskeleton, and a
      modulation of sodium pump activity.

PMID- 9004090
TI  - Microalbuminuria in essential hypertension.
AB  - The prevalence of microalbuminuria in patients with essential hypertension ranges
      between 10 and 25%. The level of albuminuria is highly correlated with arterial
      pressure and more closely ambulatory arterial pressure. The interaction between
      albuminuria and arterial pressure is clearly enhanced by overweight and smoking.
      The renal mechanisms of microalbuminuria are not well elucidated; an increase in
      filtration fraction suggestive of intraglomerular hypertension was observed in
      patients with hyperfiltration. The significance of micro-albuminuria as a marker
      of cardiovascular risk or hypertensive renal disease needs to be confirmed
      through long-term follow-up studies. Antihypertensive treatment has variable
      influence on albuminuria; angiotensin-converting enzyme inhibitors, in contrast
      to other agents, tend to partially correct this abnormality.

PMID- 9004091
TI  - Impact of antihypertensive therapy on progression of experimental renal disease.
AB  - Hypertension is common in patients with renal disease and, when uncontrolled,
      accelerates the rate of progression to end stage renal failure. There is
      considerable evidence that antihypertensive therapy can slow the rate of decline
      in kidney function in these patients. However, controversy exists regarding the
      mechanisms by which antihypertensive agents prevent kidney damage as well as the
      relative utility of different classes of drugs. This paper will focus on a series
      of studies, including several conducted in our laboratory, in which the impact of
      antihypertensive agents on kidney structure and function have been examined in
      experimental models of progressive kidney failure. Taken together, these studies
      suggest that most drugs that reduce systemic blood pressure will also lessen
      kidney damage, albeit to varying degrees and by different mechanisms.

PMID- 9004092
TI  - Titrating for antiproteinuric effect: the clue to renoprotection?
AB  - Proteinuria may be involved in the final common pathway of progressive renal
      function loss. If so, intervention treatment that reduces proteinuria might
      prevent or retard long-term renal function loss. In renal patients and in
      experimental renal disease the severity of proteinuria is associated with the
      rate of long-term renal function loss. Several large trials on the prevention of
      long-term renal function loss by antihypertensive treatment with ACE inhibitors
      (ACEi), were recently completed in diabetic and in non-diabetic renal disease. In
      those studies long-term renal function loss could indeed be retarded by ACEi;
      these ACEi regimens were associated with a more effective reduction of
      proteinuria than control regimens. In studies with a single treatment regimen
      (drug treatment or a protein restricted diet) a more effective reduction of
      proteinuria is associated with a more favourable long-term course of renal
      function as well. As reduction of proteinuria is mostly associated with a lower
      blood pressure (BP) the respective contributions of the fall in BP and in
      proteinuria are hard to dissect. Remarkably, however, the efficacy of the
      reduction of proteinuria (but not of BP) at onset of antihypertensive treatment
      is predictive of long-term renal outcome. Albeit consistent with a causal role of
      proteinuria reduction in renoprotection these data cannot distinguish between
      proteinuria as a marker or a mediator of renal damage. In view of the consistent
      association of antiproteinuric efficacy with long-term renal outcome we suggest
      that it would be worthwhile to attempt to improve long-term renoprotection by a
      strategy aimed at enhancing antiproteinuric efficacy. This approach is feasible
      as antiproteinuric efficacy of ACEi can be enhanced in several ways, ie, by
      dietary sodium and protein restriction and by adding a diuretic or indomethacin.
      Such a strategy would require that titration for adequate BP control is followed
      by titration for a maximal antiproteinuric effect. If this treatment strategy
      would improve long-term renal outcome, it would not only be a step forward in the
      clinical treatment of chronic renal failure, but it would also provide compelling
      evidence for a causal role of proteinuria in the progression of renal disease.

PMID- 9004093
TI  - The treatment of hypertension in diabetic nephropathy.

PMID- 9004094
TI  - Recent data on hypertension and progressive renal disease.
AB  - Arterial hypertension may favour the progression of non-diabetic primary renal
      disease and participate in the appearance of atheromatous renovascular disease.
      In AIPRI trial (ACE-inhibition in the progression of renal insufficiency) the ACE
      inhibitor benazepril was able to protect patients with mild-to-moderate renal
      disease against the progression of renal insufficiency. Some clinical
      observations suggest that in many aged patients with long-standing hypertension
      the appearance of renal failure may be related to atheromatous reno-vascular
      disease. This disease may be responsible for progressive renal failure through
      renal artery stenosis and/or cholesterol microembolization.

PMID- 9004095
TI  - The role of blood pressure as a risk factor for renal disease: a review of the
      epidemiologic evidence.
AB  - The aim of the paper is to examine the relationship between blood pressure (BP)
      and renal disease with an overview of observational and experimental
      investigations, with the emphasis on studies that provide data obtained in
      unselected population samples. We have found an increasing body of evidence from
      cross-sectional, case-control, prospective, and experimental studies that
      indicate BP is an important, independent predictor of both increased relative and
      attributable risk of renal insufficiency and end-stage renal disease. The
      relationship between BP and subsequent renal disease appears to be positive and
      continuous throughout the entire range of BP. Furthermore, the data indicate that
      elevations in systolic BP (SBP) are stronger predictors of risk compared to
      corresponding increases in diastolic BP (DBP). Clinical trials experience
      suggests that reduction in BP decreases the risk of subsequent renal disease.
      Ongoing trials should help to clarify issues related to choice of
      antihypertensive therapy and optimal goals for reduction of BP in order to
      prevent renal disease.

PMID- 9004096
TI  - 'Benign' essential hypertension and kidney damage: a histopathologist's view.
AB  - The kidney is damaged in people with hypertension and clinical renal disorders.
      The damage may be explained by chronic renal ischaemia, but there is no rigorous
      proof that hypertension damages a previously normal kidney. Indeed there are
      ideas that the kidney is abnormal from the start in hypertensive people.

PMID- 9004098
TI  - Tribute to Professor Antony Raine. Hypertension and the kidney: the Tony Raine
      Memorial Symposium. Glasgow, Friday 28th June 1996.

PMID- 9004097
TI  - Does non-malignant essential hypertension cause renal damage? A clinician's view.
AB  - Clinical research amongst hypertensive patients, randomised controlled trials,
      and population studies confined to white communities all show scant evidence that
      'essential' non-malignant non-proteinuric normo-creatininaemic hypertension leads
      to renal impairment. Retrospective data from dialysis and transplantation units
      also tend to confirm this point. The only convincing exception is in studies of
      African Americans where there does appear to be a relationship between blood
      pressure (BP) at screening and the subsequent development of renal impairment.
      However, it is not possible to be certain that those patients who develop renal
      impairment might not have had a low grade sub clinical glomerulonephritis when
      first seen. One must conclude, therefore, that if benign essential hypertension
      does damage the kidneys, it does so very rarely. In that respect the epidemiology
      of hypertension-induced renal damage is different from that of coronary heart
      disease and stroke. Additional and novel risk factors need to be sought.

PMID- 9004099
TI  - Riva-Rocci centenary exhibition: on the occasion of the 16th scientific meeting
      of the International Society of Hypertension in Glasgow, 23-27 June 1996.

PMID- 9004100
TI  - The sphygmomanometer of Riva-Rocci 1896-1996.

PMID- 9004101
TI  - Commentary: do angiotensin II receptor antagonists regress left ventricular
      hypertrophy?

PMID- 9004102
TI  - Long-term effects of losartan on blood pressure and left ventricular structure in
      essential hypertension.
AB  - In a 12-week, randomized, double-blind study, 24 patients with essential
      hypertension were given the angiotensin II antagonist losartan, or the beta
      adrenoceptor blocker atenolol. Both drugs reduced blood pressure (BP) well, but
      losartan tended to reduce left ventricular mass (LVM) in contrast to atenolol.
      Following the double-blind phase 19 patients entered an open treatment period
      with losartan and additional treatment if BP was uncontrolled. LV structures were
      measured by echocardiography. The mean follow-up period was 29 +/- 2.6 (range 26
      32) months. BP was reduced from 155.6 +/- 15.6/103.4 +/- 5.2 mm Hg to 131.3 +/-
      10.5/82.7 +/- 3.3 mm Hg (P < 0.001). LV internal diameter was reduced (50.7 +/-
      4.5 to 49.1 +/- 4.0 mm; P = 0.006), while there was an increase in
      interventricular septal thickness (10.2 +/- 1.1 to 11.2 +/- 1.3 mm; P = 0.001)
      and posterior wall thickness (10.0 +/- 0.9 to 10.6 +/- 1.1 mm; P = 0.023).
      Calculated LVM was not significantly altered during the follow-up period. In
      conclusion, losartan is effective in reducing BP during long-term treatment. No
      significant effect on LVM was observed, but there was an increase in LV wall
      thickness.

PMID- 9004103
TI  - Long-term blood pressure control in older Chinese patients with isolated systolic
      hypertension: a progress report on the Syst-China trial.
AB  - This report on the ongoing double-blind placebo-controlled Syst-China trial
      investigated whether antihypertensive drug treatment based mainly on a calcium
      entry blocker and a converting enzyme inhibitor, would be suitable for
      maintaining long-term blood pressure (BP) control in older Chinese patients
      (average age: 67 years) with isolated systolic hypertension (systolic pressure
      160-219 mm Hg and diastolic pressure < 95 mm Hg). Active treatment consisted of
      nitrendipine (10- 40 mg/day) with the possible addition of captopril (12.5- 50
      mg/day) and hydrochlorothiazide (12.5-50 mg/day), as necessary to reduce systolic
      pressure to a level of 150 mm Hg or lower and by at least 20 mm Hg. Matching
      placebos were used in the control group. This progress analysis was restricted to
      BP control up to 3 years of follow-up. The placebo (n = 1134) and active
      treatment n = 1245) groups had similar characteristics at enrolment. The sitting
      BP averaged 170/86 mm Hg. Systolic pressure fell (P < 0.001) on average 8 mm Hg
      more on active treatment than on placebo and diastolic pressure 3 mm Hg more.
      Fewer patients remained on monotherapy in the placebo than in the active
      treatment group (P < 0.001); on placebo the second and third line medications
      were started more frequently (P < 0.001). This progress report showed that
      significant BP reduction can be achieved and maintained in older Chinese patients
      treated with a calcium antagonist, associated with a converting-enzyme inhibitor
      and a thiazide, as necessary. Whether this BP reduction would result in a
      clinically meaningful decrease of cardiovascular complications is still under
      investigation.

PMID- 9004104
TI  - Hypertension in Haitians: results of a pilot survey of a public teaching hospital
      multispecialty clinic.
AB  - Little is known about hypertension in Haitians. We performed a pilot survey of
      ambulatory Haitian patients in a multispecialty clinic at a large public teaching
      hospital. Approximately 10% of the clinic population was of Haitian origin.
      Clinical data were collected on 88 consecutive Haitian patients. Of these 88, 77
      (87.5%) were hypertensive (SBP > or = 140 or DBP > or = 90 mm Hg or taking
      antihypertensive medication). The characteristics of the hypertensive patients
      were: age 54.1 +/- 13.0 (s.d.) years; 27 men, 50 women; 12/64 (19%) smoked; 7/63
      (11%) used alcohol. Diabetes was present in 21/77 (27%). In patients for whom
      height and weight were available, obesity was present in 52%. Using JNC V
      criteria, 18 (23%) had Stage 1, 16 (21%) Stage 2, 18 (23%) Stage 3, and 25 (33%)
      Stage 4 hypertension. Despite 63/77 (82%) being treated for hypertension, only 20
      (26%) were controlled (< 140/< 90 mm Hg). Of those under treatment, 29 were
      taking one drug; 18 (two drugs); 12 (three drugs); and four (four drugs). Target
      organ damage was evident in 37 (48%), including coronary artery disease (8), CHF
      (6), chronic renal failure (15), stroke (9), and LVH by ECG (19). There was
      evidence of severe noncompliance in 32 (42%). We conclude that in this clinic
      sample, hypertension was highly prevalent and unusually severe in terms of blood
      pressure (BP) level, refractoriness to treatment, and target organ consequences.
      Further studies are indicated.

PMID- 9004106
TI  - Low testosterone and insulin resistance in hypertension-prone men.
AB  - The aim of the study was to elucidate the relationship between peripheral insulin
      sensitivity and testosterone and sex hormone binding globulin (SHBG) in the
      development of hypertension. An euglycaemic hyperinsulinaemic clamp was performed
      to determine insulin sensitivity and sex steroid hormones and SHBG were analysed
      in 35 normotensive men with a family history of hypertension (relatives) and 27
      age and body mass index matched controls (controls). Relatives had lower
      concentrations of serum total testosterone and SHBG, and lower insulin
      sensitivity compared to controls. Free testosterone concentrations were the same
      in both groups. Relatives had lower maximal oxygen uptake compared to controls.
      Total testosterone and SHBG were correlated to basal insulin concentration and
      insulin sensitivity in relatives, but not in controls. In stepwise regression
      analysis, total testosterone explained 37% and walst circumference 6% of the
      variation of insulin sensitivity in relatives, and walst circumference explained
      29% in controls. When substituting testosterone with SHBG in this model, SHBG
      explained 48% of the variation in insulin sensitivity in relatives. The finding
      of a closer relationship between insulin sensitivity and SHBG than between
      insulin sensitivity and total testosterone suggests that the SHBG level is
      primarily influenced by insulin sensitivity in the relatives.

PMID- 9004105
TI  - Hemodynamic effects of aerobic vs resistance exercise.
AB  - Previous studies suggest that aerobic exercise lowers blood pressure (BP), while
      isometric exercise increases BP, at least transiently. The purpose of this study
      was to examine the hemodynamic effect of a 6-week training period of aerobic
      exercise or weight training. Twenty deconditioned healthy males ages 18-36, self
      selected a training regimen. The aerobic group exercised 30 min/day, 4 times each
      week to achieve 60-80% maximal heart rate. The resistance group lifted weights at
      65-80% maximal voluntary contraction; 3-4 sets of 8-12 repetitions; 3 day/week
      using large muscle groups. Hemodynamic measurements of heart rate, BP, venous
      capacitance, forearm blood flow, and vascular resistance were made at baseline
      and week 6 by plethysmography and analyzed by 2-way ANOVA. The groups showed no
      differences in baseline characteristics. A training effect was confirmed by a
      decrease in resting heart rate in the aerobic group (71.5 +/- 4.4 to 64.5 +/-
      3.7, beats per minute, P = 0.004), and an increase in total work capacity in the
      weight lifting group (6231 vs 7508, P = 0.01). Forearm blood flow increased
      similarly in both groups, averaging 17% (3.5 +/- 0.2 vs 4.2 +/- 0.2 ml 100 g/min,
      P = 0.03), while forearm vascular resistance fell 19% (28.8 +/- 1.7 vs 24.3 +/-
      1.7 mm Hg/ml/min 100 g, P = 0.08). The main differences between the groups after
      training was found in their response to isometric stress (1/3 maximal handgrip).
      The weight-lifting group had a greater increase of forearm blood flow and venous
      capacitance, less increase in systolic BP (SBP) and a greater fall of forearm
      vascular resistance, (P < 0.05) while the aerobic group had less increase in SBP
      and heart rate (P < 0.04) but no significant change of forearm hemodynamics. We
      conclude that both aerobic and repetitive weight programs have short term
      favorable effects on resting forearm BP and resistance. The exercise programs
      differ in altering the individual's physiologic response to subsequent isometric
      stress. However, exercise training of longer duration or greater intensity or
      frequency could alter these results.

PMID- 9004108
TI  - Evaluation of enalapril/diltiazem ER in hypertensive patients with coexisting
      renal dysfunction. Enalapril/Diltiazem ER in Hypertensive Renal Disease Group.
AB  - Both enalapril and long-acting diltiazem have been shown to effectively lower
      blood pressure (BP) in hypertensive patients. Furthermore, in clinical studies,
      these two agents provided beneficial renal effects in these patients when
      administered on a long-term basis. A combination of enalapril/diltiazem ER was
      evaluated in 62 patients with Stage 1-3 hypertension and coexisting renal
      disease. This trial used a multicenter, randomized, double-blind, parallel group
      design. The study consisted of a 12-week double-blind phase followed by a 6-month
      open-label extension phase. The combination of enalapril/diltiazem ER was shown
      to reduce BP following both short-term and long-term treatment phases. Patients
      in Renal Group I (creatinine clearance CrCl): 30-59 ml/min/1.73 m2) had decreases
      of -18/-16 and -25/-20 mm Hg after 12 weeks and 9 months of therapy,
      respectively. Those in Renal Group II (CrCl: 10-29 ml/min/1.73 m2) had similar
      decreases of -23/-18 and -23/-19 mm Hg at these time points. The adverse events,
      in both phases, were those associated with the respective monotherapies. A
      reduction in CrCl with a coincident decrease in proteinuria was noted for both
      renal groups. The combination of enalapril/diltiazem ER lowered BP and was
      generally well tolerated by the patients. The combination of these two agents
      should improve the management of hypertensive patients.

PMID- 9004107
TI  - Indomethacin does not attenuate the hypotensive effect of trandolapril.
AB  - This is a randomised, double-blind, placebo-controlled, four-way crossover study
      to determine if indomethacin attenuates the hypotensive effect of trandolapril.
      Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115)
      requiring NSAID were recruited. Seventeen completed the study. Three week
      treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril
      2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and
      ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5
      mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98
      mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm
      Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin;
      148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo;
      and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and
      placebo. There were no significant interactions between trandolapril and
      indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87).
      When trandolapril treatments (placebo or with indomethacin) were compared to
      treatments without trandolapril (placebo or indomethacin), trandolapril lowered
      clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean
      ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg
      (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo);
      147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and
      placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared
      with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P =
      0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered
      clinic SBP and ambulatory BP, but indomethacin did not attenuate this.
      Indomethacin had no significant effect on either clinic or ambulatory BP. The
      antihypertensive effects of trandolapril in this study were modest. Patient
      selection factors may have contributed to the observed responses, but it seems
      unlikely from these data that a clinically important drug interaction has
      occurred.

PMID- 9004109
TI  - The potentials of virtual environments in the education and training of people
      with learning disabilities.
AB  - The expansion of 'care in the community' has highlighted the need for more
      effective educational and training media for people with learning disabilities,
      and this paper suggests that virtual environments (VEs) may help to meet this
      need. Firstly, key terms (virtual environment, cyberspace and artificial reality)
      are defined. Secondly, aspects of developmental and cognitive psychological
      theories and principles of computer-assisted learning are presented that suggest
      that VEs might be an especially valuable educational media for people with
      learning disabilities. Thirdly, the existing literature in this field is
      reviewed. Fourthly, ethical issues associated with the use of VE, both generally
      and specifically by people with learning disabilities are discussed. Fifth,
      possible future developments of VEs, both in education and through their
      convergence with technologies of miniaturization, are suggested. It is concluded
      that VEs are an effective, affordable, accessible and safe training and
      educational media for people with learning disabilities, although further
      research will be required to realise their full potentials.

PMID- 9004110
TI  - The effect of buspirone on challenging behaviour in mentally retarded patients:
      an open prospective multiple-case study.
AB  - During the past few decades, suggestive evidence has been accumulated that
      abnormalities in serotonin neurotransmission are involved in the pathogenesis of
      aggressive behaviour disorders and impulsivity. Support for this idea can be
      derived from clinical studies using 5-HT1 agonistic compounds and serotonergic
      antidepressants. In the present study, the efficacy of the 5-HT1a agonist
      buspirone was investigated in eight patients with mental retardation and severe,
      long-lasting challenging behaviour, characterized by aggressive outbursts, self
      injurious behaviour and impulsivity. The findings demonstrate that buspirone, in
      a daily dosage varying between 20 and 50 mg, may be effective in reducing this
      type of behavioural disturbance and associated with an improvement in
      sociability. It is hypothesized that the responsiveness to buspirone treatment
      may be the result of a de-arousing phenomenon, mediated via corticosteroid
      dependent stress homeostatic mechanisms.

PMID- 9004111
TI  - Hypothalamic versus pituitary dysfunction in Down's syndrome as cause of growth
      retardation.
AB  - We have found that some children with Down's syndrome (DS) have growth
      retardation secondary to growth hormone (GH) deficiency. To test the hypothesis
      that hypothalamic dysfunction is the primary cause for GH deficiency and growth
      retardation, hypothalamic-pituitary responses of serum GH concentrations to
      levodopa and clonidine as well as pituitary responses in serum GH concentrations
      to growth-hormone-releasing hormone (GHRH) were analysed in 14 prepubertal
      children with DS. Levodopa and clonidine were given, and blood was drawn for
      determining serum GH levels. Seven prepubertal control children had both levodopa
      and clonidine tests done. The delta serum GH during levodopa was 5.7 +/- 6.3 ng
      ml-1 in DS and 13.1 +/- 9.8 ng ml-1 in controls. The delta serum GH during
      clonidine administration was 3.0 +/- 3.2 ng ml-1 in DS and 17.3 +/- 5.6 ng ml-1
      in controls. Children with DS had a significantly lower response to levodopa and
      clonidine, compared with controls by the Mann-Whitney U-test (P < 0.03 and P <
      0.009, respectively). Growth-hormone-releasing hormone was given at 1 microgram
      kg-1 i.v. bolus and bloods for GH were drawn at-15, 0, 15, 30, 60, 90 and 120 min
      in 14 subjects with DS and 24 normal controls, both groups prepubertal. The mean
      delta serum GH concentration in DS was 53.6 +/- 38.3 ng ml-1, and it was 35.6 +/-
      25.1 ng ml-1 in controls with P < 0.23 non-significant by the Mann-Whitney U
      test. These results indicate that levodopa and clonidine (drugs stimulating
      hypothalamic GHRH release and secondary pituitary GH release in normal
      individuals) do not stimulate GH release in DS. Furthermore, normal GH response
      to GHRH in DS indicates normal pituitary function (normal somatotroph response to
      GHRH) and supports hypothalamic dysfunction in DS.

PMID- 9004112
TI  - Severe sleep disturbance and daytime challenging behaviour in children with
      severe learning disabilities.
AB  - Sleep problems are common in children with severe learning difficulties. Children
      with sleep problems are reported to have more behaviour problems, but daytime
      challenging behaviour has not been examined specifically. The current study was
      concerned with associations between sleep problems and challenging behaviour, as
      well as describing other clinical features of the childrens' sleep, as reported
      by parents. All children in the series showed some form of sleep disturbance,
      with settling problems, night waking and early waking in 44% of the sample.
      Children with sleep problems showed significantly more types of challenging
      behaviour and challenging behaviour of a greater severity than children without
      sleep problems, resulting in management difficulties for carers throughout the 24
      h period. Reasons for this association and suggestions for intervention are
      discussed.

PMID- 9004113
TI  - Predictive value of age of walking for later motor performance in children with
      mental retardation.
AB  - The purpose of the present study was to clarify the predictive value of age of
      walking for later motor performance in children with mental retardation. While
      paying due attention to other factors, our investigation focused on the
      relationship between a subject's age of walking, and his or her subsequent beam
      walking performance. The subjects were 85 children with mental retardation with
      an average age of 13 years and 3 months. Beam-walking performance was measured by
      a procedure developed by the authors. Five low beams (5 cm) which varied in width
      (12.5, 10, 7.5, 5 and 2.5 cm) were employed. The performance of subjects was
      scored from zero to five points according to the width of the beam that they were
      able to walk without falling off. From the results of multiple regression
      analysis, three independent variables were found to be significantly related to
      beam-walking performance. The age of walking was the most basic variable: partial
      correlation coefficient (PCC) = -45; standardized partial regression coefficient
      (SPRC) = -0.41. The next variable in importance was walking duration (PCC = 0.38;
      SPRC = 0.31). The autism variable also contributed significantly (PCC = 0.28;
      SPRC = 0.22). Therefore, within the age range used in the present study, the age
      of walking in children with mental retardation was thought to have sufficient
      predictive value, even when the variables which might have possibly affected
      their subsequent performance were taken into consideration; the earlier the age
      of walking, the better the beam-walking performance.

PMID- 9004114
TI  - Care dependence and activities of daily living in relation to ageing: results of
      a longitudinal study.
AB  - From 1990 to 1993, the University of Limburg and the Pepijn Centre, the
      Netherlands, have performed a prospective cohort study on ageing and intellectual
      disability. The key questions of the study were: "To what degree do the level of
      care dependence and activities of daily living (ADL) differ between age groups,
      and to what degree do these skills change during the study period (3 years)? Are
      the changes age related?'. Looking at the changes in time, the results show that
      the level of care dependence did not change substantially in the sample of 1602
      residents of Dutch facilities for people with intellectual disability. Only the
      oldest residents (70+ years) showed a significant decline in independence. The
      results also show that the skills of young people with Down's syndrome (< 40
      years) did not change substantially, whereas older people with Down's syndrome
      (40+ years) showed a substantial decrease in ADL-skills. The ADL-skills of the
      residents with other aetiological diagnoses younger than 60 years of age did not
      change substantially, while the older residents (60-69 and 70+ years) showed a
      significant decrease in ADL-functions. The trend between changes in ADL and age
      in both aetiological groups was statistically significant. Attention is paid to
      the implications of these findings in the discussion.

PMID- 9004115
TI  - The effects of experience and sexual abuse training on the attitudes of learning
      disability staff.
AB  - Staff employed in three day centres for people with learning disabilities were
      offered training in sexual abuse. Their knowledge and attitudes about sexual
      abuse were measured immediately before and after training. Staff were asked about
      their perceptions of the risks of people with learning disabilities being
      sexually abused, and their estimations of the probability of the perpetrator
      being either a member of staff, a client, a person known to the abused person or
      a stranger. Their responses were found to be influenced by the recent training
      and their prior personal experience.

PMID- 9004116
TI  - Comparison of the types of child utterances mothers expand in children with
      language delays and with Down's syndrome.
AB  - Sixteen children with language delays and their mothers were studied to identify
      the types of child utterances mothers were most likely to expand. Eight of these
      children had Down's syndrome (DS), while the other eight were pairwise-matched
      for mean length of utterance (MLU) and did not have DS, but were language
      delayed. Twenty-minute mother-child free-play sessions were videotaped and
      transcribed. Trained observers coded utterances for child intelligibility, child
      utterance length, adult expansions and adult non-expansions. Sequential analysis
      results indicated that mothers of children with DS were more likely to expand
      partially intelligible multi-word utterances than to expand fully intelligible
      multi-word utterances. The opposite pattern occurred in the dyads without DS.
      Single-word utterances were least likely to be expanded in both groups. The
      implications of the results for language intervention and future research are
      discussed.

PMID- 9004117
TI  - Costs and recurrences of chiropractic and medical episodes of low-back care.
AB  - OBJECTIVE: To compare health insurance payments and patient outcomes for
      recurrent episodes of care for nine common lumbar and low-back conditions
      initiated with chiropractic treatment vs. episodes initiated with medical
      treatment. DATA AND METHODS: Retrospective analysis of episodes constructed using
      208 ICD-9-CM codes from 2 yr of insurance claims data for a large population of
      beneficiaries in the private fee-for-service sector. A total of 7077 patients
      were represented within 9314 episodes of care, of which 8018 episodes were
      initiated by clearly identified chiropractic or medical physicians. There were
      1215 patients with initial physician or chiropractic-initiated episodes who had
      recurrent episodes. Outcome measures included total insurance payments, total
      outpatient payments, lengths of initial and recurrent episodes, consistent use of
      initiating providers for recurrent episodes and time lapsed between episodes.
      RESULTS: Total insurance payments within and across episodes were substantially
      greater for medically initiated episodes. Analysis of recurrent episodes as
      measures of patient outcomes indicated that chiropractic providers retain more
      patients for subsequent episodes, but that there is no significant difference in
      lapse time between episodes for chiropractic vs. medical providers. Chiropractic
      and medical patients were comparable on measures of severity; however, the
      chiropractic cohort included a greater proportion of chronic cases. CONCLUSION:
      Patients who "cross over" between providers for multiple episodes are more likely
      to return to chiropractic providers, which suggests that chronic, recurrent low
      back cases may gravitate to chiropractic care over time. The findings from this
      and related studies point out the importance of appropriately operationalizing
      cost and outcome variables in analyses of care for conditions such as chronic
      and/or recurrent low-back pain.

PMID- 9004118
TI  - Establishment of total and intraservice work by chiropractic physicians in
      providing spinal manipulative therapy and evaluation and management services.
AB  - OBJECTIVE: To develop and test a self-report survey instrument that measures the
      work performed by chiropractors in the delivery of evaluation and management
      (E/M) services and spinal manipulative therapy (SMT). Work is one leg of a triad
      used to develop Resource-Based Relative Values Scales (RBRVS) for physician
      reimbursement. DESIGN: Reliability study modeled after a tool designed and tested
      by economists at Harvard University School of Public Health in the development of
      relative values scales for physician reimbursement. The survey instrument uses
      magnitude estimation as a means of obtaining reliable and valid measures of the
      subjective assessments of the dimensions of a physicians work. SAMPLE: A random
      national sample was drawn from all members of the American Chiropractic
      Association. RESULTS: Estimates of the work performed by chiropractors in
      providing E/M and SMT services were established. The reliability of work ratings
      indicated that chiropractors agree closely on their ratings for work. The
      validity of the results indicated a high degree of consistency in rating work,
      which implies that the results are realistic. A review of demographics suggested
      that the survey population was representative of the general population of
      chiropractors. CONCLUSIONS: This study generated valid and reliable estimates of
      the work performed by chiropractors in providing E/M and SMT services. Work is
      one of three components used in the development of RBRVS, the method of physician
      reimbursement that is currently the industry standard. By quantifying the work
      required in providing services, chiropractors can now develop RBRVS.
      Additionally, the evidence-based data on work collected here can be used for a
      comparison with the work of similar services provided by other specialists. This
      can facilitate the use or modification of service description codes for use by
      chiropractic physicians.

PMID- 9004119
TI  - Chronic neck pain, standing balance, and suboccipital muscle atrophy--a pilot
      study.
AB  - OBJECTIVE: To study the relationship between chronic neck pain, standing balance
      and suboccipital muscle atrophy. We hypothesize that patients with chronic neck
      pain have more somatic dysfunction in the cervical spine than control subjects
      without neck pain. We also hypothesize that patients with chronic neck pain and
      somatic dysfunction exhibit more atrophy of suboccipital muscles. Lastly, because
      suboccipital muscles have a high density of proprioceptors, we hypothesize that
      chronic pain patients exhibit a loss in standing balance. DESIGN: Randomized,
      controlled, partially blind study examining chronic neck pain patients and
      control subjects for differences in degree of upper cervical somatic dysfunction,
      standing balance and suboccipital muscle atrophy. SETTING: Subjects were
      recruited from a clinical practice at Michigan State University; controls were
      recruited from the faculty, staff and students. PARTICIPANTS: Seven chronic neck
      pain patients and seven asymptomatic control subjects. MAIN OUTCOME MEASURES:
      Palpation was used to diagnose somatic dysfunction in the upper cervical spine.
      Balance parameters were calculated using a force platform; muscle atrophy was
      judged with magnetic resonance images. RESULTS: Chronic neck pain patients had
      almost twice as many somatic dysfunctions as controls (p = .028). Force platform
      results showed a decrease in standing balance in patients compared with control
      subjects (p = .004). MRI showed that chronic neck pain subjects had marked
      atrophy of the rectus capitis posterior major and minor muscles, including fatty
      infiltration. CONCLUSIONS: This study suggests that there is a relationship
      between chronic pain, somatic dysfunction, muscle atrophy and standing balance.
      We hypothesize a cycle initiated by chronic somatic dysfunction, which may result
      in muscle atrophy, which can be further expected to reduce proprioceptive output
      from atrophied muscles. The lack of proprioceptive inhibition of nociceptors at
      the dorsal horn of the spinal cord would result in chronic pain and a loss of
      standing balance.

PMID- 9004120
TI  - Movements of vertebrae during manipulative thrusts to unembalmed human cadavers.
AB  - OBJECTIVE: The purpose of this study was to measure the relative movements of
      vertebrae during manipulative thrusts to unembalmed post-rigor mortis human
      cadavers. SETTING: The investigation was conducted in the gross anatomy
      laboratory at the University of Calgary. SUBJECTS: Two 77-yr-old, unembalmed,
      post-rigor mortis, male cadavers were used. INTERVENTIONS: The movements of
      vertebrae were investigated by using high-speed cinematography to record the
      movements of bone pins threaded into T10, T11 and T12 during spinal manipulative
      therapy to unembalmed post-rigor human cadavers. A single clinician delivered a
      series of posterior-to-anterior (p-to-a) thrusts to the right transverse process
      of either T10, T11 or T12, using a reinforced hypothenar contact. Relative p-to-a
      and lateral translations, as well as axial and sagittal rotations, in T10-T11 and
      T11-T12 were calculated. Corresponding p-to-a forces exerted by the clinician
      onto the cadaver were recorded using a pressure pad. MAIN RESULTS: Significant
      relative movements were measured primarily between the targeted and immediately
      adjacent vertebrae during the thrusts. Vertebral pairs remained slightly 'hyper
      extended' after the rapid thrusts to T11, when the p-to-a forces returned to
      preload levels. CONCLUSIONS: These findings may be useful for the understanding
      of the deformation behavior of the vertebral column during therapeutic
      manipulation. A fully three-dimensional analysis of all six degrees of freedom,
      using a larger number of unembalmed cadavers, would be useful in clarifying the
      relationship between the externally applied forces and the observed relative
      movement patterns of the vertebrae.

PMID- 9004121
TI  - Self-directed patient education in soft-tissue rehabilitation: rationale and
      analysis of a pilot project.
AB  - OBJECTIVES: To determine the compliance level and topic choice selection
      frequency of rehabilitation patients in a self-directed education program offered
      in conjunction with a rehabilitation exercise program. DESIGN: Descriptive study.
      SETTING: Soft-tissue injury rehabilitation clinic located within a chiropractic
      college. SUBJECTS: Twenty-four rehabilitation patients with injured spines who
      were enrolled in a daily in-clinic program. OUTCOME MEASURES: Data was collected
      from patient log-book pages, which recorded frequency of use, topic, medium and
      personal satisfaction for each selected resource. Clinic attendance data was
      collected by the clinical staff. RESULTS: Eighty-one percent (81%) of the patient
      group voluntarily used the learning center. Average frequency of use was
      approximately one visit per patient per week. Of the 13 subject areas included in
      the resource center collection, back injury care (30), nutrition (22) and
      fitness/exercise (14) received the most use. Patient satisfaction with the
      resources' value/interest averaged 78.4%. CONCLUSIONS: Most (81%) patients in
      this group were willing to spend some of their own time learning information that
      they thought was important. The results may allow for patient education program
      designs that put more responsibility for learning with the patient and allow for
      more efficient clinician time allocation.

PMID- 9004122
TI  - Arterial tonometry and assessment of cardiovascular alterations with chiropractic
      spinal manipulative therapy.
AB  - OBJECTIVES: To (a) introduce arterial tonometry, which may offer a greater
      opportunity to detect alterations of the cardiovascular system with spinal
      manipulative therapy, (b) discuss the limitations of standard blood pressure
      measurements and (c) discuss factors that govern the contour of arterial pressure
      pulses. DATA SOURCES: Information was obtained from peer-reviewed medical and
      chiropractic journal articles and medical textbooks written in English (mainly
      from 1980 to 1995). CONCLUSIONS: Arterial tonometry is a noninvasive method to
      continuously measure the contour of arterial pressure pulses. Pulses can be
      simultaneously measured from several arterial sites because vessel occlusion is
      not required. Arterial tonometry supplements standard blood pressure measurements
      that measure only the systolic and diastolic pressures by permitting the
      investigation of additional parameters of cardiovascular functions. Changes in
      large artery function can be inferred through alterations of pulse contour, wave
      velocity and harmonic transmission ratios. Analysis of the beat-to-beat
      fluctuations of arterial pressure and heart rate can be used to determine whether
      SMT alters the autonomic nervous system. Reductions of arterial pressure in
      central vessels may not be apparent from standard blood pressure measurements at
      peripheral vessels. The contour of a pressure pulse depends on the magnitude and
      timing between incident and reflected pressure waves from the upper and lower
      body, body shape and size, the duration and pattern of ventricular systole, and
      dispersion and attenuation. Therefore, arterial tonometry may improve the ability
      to detect alterations of the cardiovascular system in chiropractic research.

PMID- 9004123
TI  - Bone marrow edema caused by altered pedal biomechanics.
AB  - OBJECTIVE: To review the magnetic resonance imaging (MRI) appearance of bone
      marrow edema (BME) and to discuss the applications of this imaging modality in
      the diagnosis of associated disorders. A case of BME in the foot is also provided
      to acquaint the reader with how MRI may assist in establishing a differential
      diagnosis in patients with normal radiographs and clinical findings that suggest
      osseous injury. CLINICAL FEATURES: A 42-yr-old woman suffered from persistent
      pain along the dorsum of her foot that worsened with jogging. There was foot
      pronation and palpable pain and swelling at the third tarsometatarsal joint. An
      MRI was performed, but it was initially misinterpreted. A second review of the
      MRI examination established the presence of stress-induced BME adjacent to the
      articular margins of the third tarsometatarsal joint. INTERVENTION AND OUTCOME:
      Medical treatment consisted of a cortisone injection into the left third
      tarsometatarsal joint, which provided transient relief. Chiropractic treatment
      included flexible custom orthotics prescribed to specifically address her foot
      pronation. This was the only chiropractic treatment employed. CONCLUSION: In the
      presented case, the sensitivity of MRI to stress-induced BME identified the cause
      of this patient's symptoms and, more importantly, directed management. Because of
      its ability to demonstrate anatomic and physiologic information, MRI is the ideal
      imaging modality for assessing suspected injury to the osseous tissues. In
      patients who relay historical information that suggests chronic or acute osseous
      injury but demonstrate no radiographic changes to support the clinical suspicion
      of bony abnormality, an MRI may be indicated to exclude occult injury.

PMID- 9004124
TI  - Most common causes of chiropractic malpractice lawsuits.

PMID- 9004125
TI  - The validity of the extension-rotation test as a clinical screening procedure
      before neck manipulation: a secondary analysis.

PMID- 9004126
TI  - Cancer families: what risks are they given and do the risks affect management?
AB  - The numbers of referrals to genetics clinics for people with a family history of
      cancer is increasing rapidly. Although it is likely that presymptomatic testing
      will soon be available for some families, for the majority of people with a
      family history of malignancy, risk can only be assessed by examining their
      pedigrees and referring to standard texts. In order to find out if clinical
      geneticists are providing consistent risks and suggestions for management we
      surveyed consultant clinical geneticists with a questionnaire about four people
      with a family history of malignancy. The clinical geneticists replying to our
      questionnaire gave consistent advice for the person with a family history of
      colon cancer, but there was wide variation in suggested risks and management for
      those with family histories of breast and multisite cancers. This survey shows
      that deciding on appropriate management for cancer families can be difficult and
      that there is uncertainty about the most effective methods of screening young
      people at high risk of developing cancers. However, it is important to provide
      consistent advice in order to evaluate screening protocols and lack of
      consistency in advice given to different family members can cause anxiety and
      distress. Consistency may be achieved by the use of one model for risk
      calculation, and by representatives from several specialties, such as surgery,
      radiology, genetics, and public health working together in order to coordinate
      local and national screening policies.

PMID- 9004128
TI  - Williams-Beuren syndrome: phenotypic variability and deletions of chromosomes 7,
      11, and 22 in a series of 52 patients.
AB  - Fluorescence in situ hybridisation (FISH) and conventional chromosome analysis
      were performed on a series of 52 patients with classical Williams-Beuren syndrome
      (WBS), suspected WBS, or supravalvular aortic stenosis (SVAS). In the classical
      WBS group, 22/23 (96%) had a submicroscopic deletion of the elastin locus on
      chromosome 7, but the remaining patient had a unique interstitial deletion of
      chromosome 11 (del(11)(q13.5q14.2)). In the suspected WBS group 2/22 (9%)
      patients had elastin deletions but a third patient had a complex karyotype
      including a ring chromosome 22 with a deletion of the long arm (r(22)(p11-
      >q13)). In the SVAS group, 1/7 (14%) had an elastin gene deletion, despite having
      normal development and minimal signs of WBS. Overall, some patients with
      submicroscopic elastin deletions have fewer features of Williams-Beuren syndrome
      than those with other cytogenetic abnormalities. These results, therefore,
      emphasise the importance of a combined conventional and molecular cytogenetic
      approach to diagnosis and suggest that the degree to which submicroscopic
      deletions of chromosome 7 extend beyond the elastin locus may explain some of the
      phenotypic variability found in Williams-Beuren syndrome.

PMID- 9004127
TI  - Microsatellite instability in early onset and familial colorectal cancer.
AB  - Hereditary non-polyposis colorectal cancer syndrome (HNPCC) is often considered
      to be the most common form of inherited colorectal cancer, although its precise
      incidence is unknown. The clinical diagnosis of HNPCC relies on a combination of
      family history and young age of onset of colorectal cancer, but as many familial
      aggregations of colorectal cancer do not fulfil the strict diagnostic criteria,
      HNPCC might be underdiagnosed. The majority of HNPCC families have germline
      mutations in mismatch repair (MMR) genes, such as MSH2 or MLH1, so that HNPCC
      cancers characteristically exhibit DNA replication errors (RERs) at
      microsatellite loci. Although an RER positive phenotype in tumours can also
      result from somatic mutations in an MMR gene, the prevalence of RER + tumours
      should provide a maximum estimate of the incidence of germline MMR gene mutations
      in patients with early onset and familial colorectal cancer. We investigated
      colorectal cancers for RERs from (1) a population based study of 33 patients with
      colorectal cancer aged 45 years or less, (2) 65 kindreds with familial colorectal
      cancer which only partially fulfilled the criteria for the diagnosis of HNPCC,
      and (3) 18 cancers from 12 HNPCC kindreds. Seven of 33 patients (21%) with
      colorectal cancer aged 45 years or less had an RER + cancer, with only two of
      these having a clear family history of HNPCC. A greater proportion of RER +
      tumours (5/7) occurred proximal to the splenic flexure than RER - tumours (4/26;
      chi2 = 6.14, p < 0.025). RERs were detected in all 18 cancers from HNPCC patients
      but in only six of 65 non-HNPCC familial colorectal cancer kindreds (9%; chi2 =
      52.2, p < 0.0005). These findings suggest that most cancers in patients diagnosed
      at 45 years of age or less and familial aggregations of colorectal cancer which
      do not fulfil HNPCC diagnostic criteria do not have germline mutations in MSH2
      and MLH1. Hence population screening for germline mutations in these genes is
      unlikely to be an efficient strategy for identifying people at high risk of
      developing colorectal cancer.

PMID- 9004129
TI  - Fine mapping of the dyskeratosis congenita locus in Xq28.
AB  - Dyskeratosis congenita (DC) is characterised by reticulate skin pigmentation,
      mucosal leucoplakia, and nail dystrophy. Bone marrow failure occurs in 50% of
      patients and is the principal cause of early mortality. In the majority of
      families the pattern of inheritance of DC is compatible with an X linked
      recessive trait. The locus for the X linked recessive form of DC has been linked
      to Xq28. We have now extended our earlier studies by investigating five families
      with additional Xq28 polymorphic markers; analysis of recombination events in
      these families has located the DC1 locus between GABRA3 and DXS1108, an interval
      of approximately 4 Mb.

PMID- 9004130
TI  - Refined mapping of a gene for split hand-split foot malformation (SHFM3) on
      chromosome 10q25.
AB  - Split hand-split foot malformation (SHFM) is a genetically heterogeneous limb
      developmental defect characterised by the absence of digital rays and syndactyly
      of the remaining digits. Three disease loci have recently been mapped to
      chromosomes 7q21 (SHFM1), Xq26 (SHFM2), and 10q25 respectively (SHFM3). We report
      the mapping of SHFM3 to chromosome 10q25 in two large SHFM families of French
      ancestry (Zmax for the combined families = 6.62 at theta = 0 for marker AFM249wc5
      at locus D10S222). Two recombinant events reduced the critical region to a 9 cM
      interval (D10S1709-D10S1663) encompassing several candidate genes including a
      paired box gene PAX2 (Zmax = 5.35 at theta = 0). The fibroblast growth factor 8
      (FGF 8), the retinol binding protein (RBP4), the zinc finger protein (ZNF32), and
      the homeobox genes HMX2 and HOX11 are also good candidates by both their position
      and their function.

PMID- 9004131
TI  - The tRNA(Gln) 4336 mitochondrial DNA variant is not a high penetrance mutation
      which predisposes to dementia before the age of 75 years.
AB  - The genetic factors that predispose to Alzheimer's disease (AD) are
      heterogeneous. Two recent reports have suggested that a mitochondrial DNA
      mutation within the tRNAGln gene, located at position 4336, may be a risk factor
      for AD, as it was found in 10/256 (3.9%) cases with AD confirmed by necropsy.
      Although low prevalences of this mutation were detected in non-demented subjects
      in both of these studies, the controls were not carefully matched with the AD
      cases. We have investigated the frequency of this mutation in two community based
      elderly cohorts in Cambridgeshire, who have participated in longitudinal studies
      of cognitive function. The 4336 mitochondrial mutation was detected in 8/ 443
      people examined. These people were found to be non-demented at ages 74, 81, 84,
      86, 89, 90, 91, and 102 years, in contrast to the previously described cases
      whose onset of dementia occurred between 60 and 76 years (mean 68). Accordingly,
      we believe that this mitochondrial variant is not a high penetrance mutation
      which predisposes to dementia before the age of 76 years.

PMID- 9004132
TI  - Variable FMR1 gene methylation of large expansions leads to variable phenotype in
      three males from one fragile X family.
AB  - The fragile X syndrome is caused by an expanded CGG repeat (> 200 units, full
      mutation) at the 5' end of the FMR1 gene, which is associated with methylation of
      a CpG island upstream of the FMR1 gene and down regulation of the transcription.
      We describe three related males with full mutations in the FMR1 gene, as defined
      by size, but with different percentages of unmethylated alleles (+/-90%, 35%, and
      15%, respectively) as studied in leucocytes. Normal mental status was observed in
      the male who showed 90% lack of methylation, whereas his two cousins were
      retarded. The mentally normal male did show some minor facial features of the
      fragile X syndrome; the FMR protein was detectable in 75% of his leucocytes. In
      all three cases, the proportion of unmethylated FMR1 genes corresponded to the
      percentage of leucocytes showing FMR1 protein production. Our results indicated a
      direct relationship between methylation and the ability to produce FMR protein.
      These cases will be discussed in relation to the phenotypic effects of
      incompletely methylated full mutations in the FMR1 gene as observed by others.

PMID- 9004134
TI  - Unexpected HLA haplotype sharing in dizygotic twin pairs discordant for
      rheumatoid arthritis.
AB  - Dizygotic twins are generally believed to be no more genetically similar than
      sibs born from separate pregnancies. In the present study, a panel of 93
      dizygotic twin pairs discordant for rheumatoid arthritis were typed for HLA-A, 
      B, -Cw, and -DR antigens. HLA haplotype sharing identical by descent between the
      twins showed a trend towards increased sharing of both HLA haplotypes; this
      increased sharing was statistically significant when the female/female twin pairs
      were considered separately. In contrast, the pattern of HLA haplotype sharing in
      sib pairs (n = 128) was consistent with a 1:2:1 ratio of 2, 1, or 0 haplotypes
      shared. An analysis of 16 normal dizygotic twin pairs was consistent with these
      results raising the possibility that dizygotic twins in general are genetically
      more similar at the HLA complex than sibs born from separate pregnancies.

PMID- 9004133
TI  - Analysis of parent of origin specific DNA methylation at SNRPN and PW71 in
      tissues: implication for prenatal diagnosis.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct developmental
      disorders caused by absence of paternal or maternal contributions of the
      chromosome region 15q11-q13, resulting from deletions, uniparental disomy (UPD),
      or rare imprinting mutations. Molecular cytogenetic diagnosis is currently
      performed using a combination of fluorescence in situ hybridisation (FISH), DNA
      polymorphism analysis, and DNA methylation analysis. Only methylation analysis
      will detect all three categories of PWS abnormalities, but its reliability in
      tissues other than peripheral blood has not been examined extensively. Therefore,
      we examined the methylation status at the CpG island of the small nuclear
      ribonucleoprotein associated polypeptide N (SNRPN) gene and at the PW71 locus
      using normal and abnormal lymphoblast (LB) cell lines (n = 48), amniotic fluid
      (AF) cell cultures (n = 25), cultured chorionic villus samples (CVS, n = 17), and
      fetal tissues (n = 18) by Southern blot analysis with methylation sensitive
      enzymes. Of these samples, 20 LB cell lines, three AF cultures, one CVS, and 15
      fetal tissues had been previously diagnosed as having deletions or UPD by other
      molecular methods. Methylation status at SNRPN showed consistent results when
      compared with FISH or DNA polymorphism analysis using all cell types tested.
      However, the methylation pattern for PW71 was inconsistent when compared with
      other tests and should therefore not be used on tissues other than peripheral
      blood. We conclude that SNRPN, but not PW71, methylation analysis may be useful
      for diagnosis of PWS/AS on LB cell lines, cultured amniotic fluid, or chorionic
      villus samples and will allow, for the first time, prenatal diagnosis for
      families known to carry imprinting centre defects.

PMID- 9004135
TI  - Evidence for compound heterozygosity causing mild and severe forms of autosomal
      recessive spinal muscular atrophy.
AB  - Spinal muscular atrophy is an autosomal recessive disease of motor neurone
      degeneration which shows a variable phenotype. Two candidate genes show deletions
      in affected subjects but with no distinction between different forms of the
      disease. We report an unusual family in which mild and severe SMA coexists and
      patients are deleted for the SMN gene. The father is affected with late onset
      SMA; therefore this family shows pseudodominant inheritance. When typed using
      closely linked flanking markers the severely affected son does not share the same
      haplotype as his sib, who is deleted for SMN but shows no signs yet of SMA. This
      supports the hypothesis that differences in SMA phenotype can be explained by a
      multiple allele model.

PMID- 9004136
TI  - A general method for the detection of large CAG repeat expansions by fluorescent
      PCR.
AB  - The expansion of a tandemly repeated trinucleotide sequence, CAG, is the
      mutational mechanism for several human genetic diseases. We present a generally
      applicable PCR amplification method using a fluorescently labelled locus specific
      primer flanking the CAG repeat together with paired primers amplifying from
      multiple priming sites within the CAG repeat. Triplet repeat primed PCR (TP PCR)
      gives a characteristic ladder on the fluorescence trace enabling the rapid
      identification of large pathogenetic CAG repeats that cannot be amplified using
      flanking primers. We used our method to test a cohort of 183 people from myotonic
      dystrophy families including unaffected subjects and spouses. Eighty five
      clinically affected subjects with expanded alleles on Southern blot analysis were
      all correctly identified by TP PCR. This method is applicable for any human
      diseases involving CAG repeat expansions.

PMID- 9004138
TI  - Lay understanding of genetics: a test of a hypothesis.
AB  - There have been growing calls for more education in genetics for the public and
      in schools. However, studies of the public, school children, and those who have
      received genetic counselling show that understanding of scientific genetics is
      very limited. A hypothesis to explain this limited understanding is proposed and
      tested. It is argued that there is a widespread lay knowledge of inheritance
      which conflicts in a number of aspects with scientific explanations and which
      impedes the assimilation of the latter. It is suggested that this lay knowledge
      is derived from concepts of the social relationships of kinship. Concepts of
      kinship ties are sustained by everyday social activities and relationships which
      may make them resistant to change. A prediction which follows from the hypothesis
      that the lay understanding of genetics is derived from concepts of family and
      kinship relationships is that closeness in genetic terms will be determined by
      the closeness of the family ties of social relationship and social obligation.
      While the proportion of genes shared with parents, children, and sibs is, on
      average, the same, kin relationships and obligations are much stronger between
      parents and children than between sibs. The hypothesis was tested in a
      questionnaire study of two samples of adult women (n = 64 and n = 113) and one of
      social science students (n = 73). In all three groups a higher proportion of
      subjects gave the correct response for the proportion of shared genes with a
      father and child than with a sister, uncle, or grandmother. In the cases of
      sisters and uncle (and grandmother), there was a consistent tendency to
      underestimate the degree of genetic connection as predicted by the hypothesis.
      Answers to other questions are consistent with the hypothesis. The fundamental
      implications of the hypothesis for genetic education in the clinic and classroom
      are outlined.

PMID- 9004137
TI  - Identification of carriers of Duchenne/Becker muscular dystrophy by a novel
      method based on detection of junction fragments in the dystrophin gene.
AB  - We developed a Southern blotting based method that uses rare cutting restriction
      endonucleases and electrophoresis of single stranded DNA to detect junction
      fragments resulting from the rearranged dystrophin gene. By conventional Southern
      blot hybridisation, no junction fragments were detected in 27 unrelated patients
      with Duchenne (DMD) or Becker (BMD) muscular dystrophy, who had 20 deletions and
      seven duplications in the dystrophin gene. With our new method, junction
      fragments were detected in 21 of these 27 patients. When the junction fragments
      were used as markers, five carriers were unequivocally diagnosed among six
      females from two families of DMD/ BMD patients. This novel method allows simple
      and definitive identification of carriers with risk factors for DMD/BMD without
      using quantitative Southern blot hybridisation.

PMID- 9004139
TI  - Pendred syndrome.

PMID- 9004140
TI  - Rapid diagnostic test for the major mutation underlying Batten disease.
AB  - Batten disease is the most common progressive neurodegenerative disorder of
      childhood in western countries. A novel cDNA responsible for Batten disease has
      recently been identified. We have developed a rapid diagnostic solid phase
      minisequencing test to detect the major 1.02 kb deletion which is responsible for
      81% of affected chromosomes in Batten disease worldwide. In Finland, 90% of
      Batten chromosomes carry the major deletion owing to the enrichment of the CLN3
      gene in the isolated Finnish population.

PMID- 9004142
TI  - Molecular cytogenetic characterisation of the first familial case of partial 9p
      duplication (p22p24).
AB  - We report on a father and daughter with a partial 9p duplication, dup(9)(p22p24).
      Their phenotype, albeit mild, is characteristic of partial trisomy 9p.
      Fluorescence in situ hybridisation (FISH) was used to characterise further and
      confirm the G banding finding. This is the first reported instance of trisomy 9p
      occurring in two successive generations. The duplicated segment in these two
      patients is among the smallest segments reported. Comparison of our two patients
      and 144 reported patients with trisomy 9p (partial or complete trisomy) suggests
      that the 9p22 region may be responsible for the observed phenotype in 9p
      duplication cases.

PMID- 9004141
TI  - Exclusion of one pedigree affected by adult onset primary open angle glaucoma
      from linkage to the juvenile glaucoma locus on chromosome 1q21-q31.
AB  - A locus for autosomal dominant juvenile onset primary open angle glaucoma (POAG)
      was recently assigned to chromosome region 1q21-q31. In the present study, a
      large Greek family with autosomal dominant adult onset POAG was investigated
      using microsatellite markers. Exclusion of linkage of the adult onset POAG gene
      to the region D1S194-D1S191 was obtained in this pedigree. Therefore, the data
      provide evidence that juvenile and adult onset POAG are genetically distinct
      disease entities.

PMID- 9004143
TI  - Dejerine-Sottas disease with sensorineural hearing loss, nystagmus, and
      peripheral facial nerve weakness: de novo dominant point mutation of the PMP22
      gene.
AB  - A 32 year old woman with Dejerine-Sottas disease and negative family history is
      reported. Clinical onset of her condition was with congenital weakness of her
      distal four extremities, accompanied by peripheral facial nerve weakness,
      deafness, and nystagmus. She has used a wheelchair all her life. Sural nerve
      biopsy showed proliferation of Schwann cells, extensive endoneural fibrosis, axon
      loss, and demyelination. MNCVs showed marked slowing. MRI of the brain was
      normal. Molecular genetic studies indicated a de novo dominant missense point
      mutation of exon 3 of the peripheral myelin protein 22 gene at nucleotide 264
      causing replacement of serine with leucine.

PMID- 9004145
TI  - Selection for presymptomatic testing for Huntington's disease: who decides? A
      reply from the Victorian Clinical Genetics Service, Murdoch Institute, Melbourne,
      Australia.

PMID- 9004144
TI  - Marfan syndrome.

PMID- 9004146
TI  - Heterotaxia syndromes and 22q11 deletion.

PMID- 9004147
TI  - First report of three cystic fibrosis patients homozygous for the 1717-1G-->A
      mutation.

PMID- 9004148
TI  - Does preconditioning act by glycogen depletion in the isolated rat heart?
AB  - Preconditioning hastens the time to onset of ischaemic contracture and increases
      peak contracture in an isolated perfused rat heart, but improves recovery of
      function. The preconditioning ischaemic episode is also known to deplete glycogen
      stores. We tested whether a depletion in glycogen is related to the protection
      conferred by preconditioning. The isolated Langendorff perfused rat heart, with a
      left ventricular balloon to record function, was perfused with either glucose 11
      mM, acetate 5 mM, or glucose 11 mM + insulin to alter pre-ischaemic glycogen
      levels prior to 30 min total global ischaemia. In addition, hearts were
      preconditioned by an episode of 5 min ischaemia and 5 min reperfusion. Time to
      onset of contracture (TOC-min), peak contracture and recovery of developed
      pressure after 20 min reperfusion with glucose-containing perfusate (both
      expressed as percentage pre-ischaemic developed pressure) were measured (n = 9
      10). Parallel groups of hearts were clamped at various times for assessment of
      tissue metabolites. Acetate pre-perfusion reduced glycogen levels compared to
      glucose hearts, from 16.27 +/- 0.44 to 10.77 +/- 0.96 mumol/g wet wt. TOC was
      reduced and peak contracture increased, with poor functional recovery. Glucose +
      insulin pre-perfusion increased glycogen (21.39 +/- 1.08 mumol/g wet wt) with
      opposite effects on contracture, but functional recovery was still poor.
      Preconditioning hastened the time to onset of contracture, which could be
      partially attributed to glycogen depletion. Preconditioning significantly
      improved functional recovery in glucose hearts, but had little or no effect in
      the other groups. Thus the protective effect on functional recovery could not be
      linked to glycogen depletion. Pre-ischaemic glycogen appeared to play a dual
      role. When low, preconditioning was ineffective, presumably because of lack of
      production of glycolytic ATP, and severe contracture. When pre-ischaemic glycogen
      was increased, preconditioning was also relatively ineffective, presumably
      because of excess accumulation of the metabolites of glycogenolysis.

PMID- 9004149
TI  - Is stunning an important component of preconditioning?
AB  - We tested the hypothesis that stunning following a brief period of ischaemia is a
      component of cardioprotection afforded by preconditioning in an in vitro model of
      global normothermic ischaemia. Isolated Langendorff-perfused rat hearts, after
      120-150 min of aerobic perfusion, were divided into four groups. Groups 1 and 2
      constituted the aerobic and ischaemic controls. The other hearts were
      preconditioned by two 2-min ischaemia/reperfusion cycles. Two ischaemic
      preconditioning protocols were used, the only difference being prolongation of
      the reperfusion cycle from 5 (group 3) to 20 min (group 4) before the onset of
      severe ischaemic insult. Mechanical function, energetic metabolism and the rate
      of enzyme release were followed throughout. In group 3, myocardial function
      remained significantly downregulated before the onset of severe ischaemia. This
      resulted in cardiac protection as evidenced by enhanced recovery of systolic
      pressure (37.7 +/- 3.6 v 61.9 +/- 5.7 mmHg for groups 2 and 3, respectively; P <
      0.02), reduced rise in diastolic pressure (55.8 +/- 5.9 v 34.3 +/- 5.2 mmHg; P <
      0.02), reduced creatine kinase (CK) release (957.3 +/- 175.7 v 541.5 +/- 85.9
      mU/min/gww; P < 0.05) and higher contents of high-energy phosphate at the end of
      ischaemia [3.6 +/- 0.3 v 25.3 +/- 2.9 mumol/gdw for creatine phosphate (CP), P <
      0.001] as well as after reperfusion (16.8 +/- 2.4 v 31.4 +/- 1.8 for CP, P <
      0.01, and 3.9 +/- 0.5 v 6.2 +/- 0.8 mumol/gdw for ATP, P < 0.05). When severe
      ischaemia was started only after complete recovery of mechanical function (group
      4), no protection was observed. Our data suggest that a decrease in mechanical
      function or stunning occurring after the short period of ischaemia causes ATP
      sparing and constitutes an additional mechanism of preconditioning
      cardioprotection in vitro.

PMID- 9004150
TI  - Bradykinin protects against infarction but does not mediate ischemic
      preconditioning in the isolated rat heart.
AB  - The aim of the study was to test if pre-ischemic treatment with bradykinin can
      protect against infarction in an isolated rat heart model of regional ischemia
      and reperfusion, and if any such protection is dependent upon activation of
      protein kinase C (PKC) or mediated through the nitric oxide (NO) pathway. We also
      investigated if bradykinin B2 receptor activation, alone or in combination with
      activation of adenosine receptors and alpha-adrenoceptors, are involved in the
      infarct size reducing effect of ischemic preconditioning. Buffer-perfused rat
      hearts were subjected to 30 min regional ischemia and 120 min reperfusion. Risk
      zone was determined by fluorescent particles and infarct size by tetrazolium
      staining. Treatment with bradykinin (0.5 mumol/l) prior to ischemia significantly
      reduced infarct size in percentage of risk zone compared to control experiments
      (infarct size: 9.6 +/- 1.3% v 41.8 +/- 3.6%, P < 0.001). An inhibitor of NO
      synthesis, NOARG (100 mumol/l), did not interfere with the bradykinin induced
      protection (infarct size: 13.3 +/- 2.0%), while chelerythrine (2 mumol/l), an
      inhibitor of protein kinase C, reversed the effect of bradykinin (infarct size:
      30.0 +/- 2.8%). NOARG did not influence infarct size in the control group
      (infarct size: 40.1 +/- 3.2%). Ischemic preconditioning with three cycles of 5
      min global ischemia + 5 min reperfusion offered protection similar to bradykinin
      (infarct size: 8.4 +/- 2.0%). The bradykinin antagonist HOE 140 (1 mumol/l)
      reversed the effect of bradykinin (infarct size: 42.5 +/- 3.1%), but did not
      interfere with ischemic preconditioning (infarct size: 7.7 +/- 1.6%). Similarily,
      combined blockade of alpha-adrenergic, adenosine and bradykinin B2 receptors with
      p-benzamine (10 mumol/l). SPT (100 mumol/l) and HOE 140 did not interfere with
      ischemic preconditioning (infarct size: 7.8 +/- 1.1%). Thus, bradykinin can
      protect against infarction via protein kinase C, but independently of NO. A role
      for bradykinin in mediating ischemic preconditioning against infarction could not
      be demonstrated.

PMID- 9004153
TI  - Hibernating myocardium: a review.
AB  - Within a few seconds after a sudden reduction of coronary blood flow regional
      contractile dysfunction ensues. The mechanisms responsible for the rapid
      reduction in contractile function during acute myocardial ischemia remain
      unclear, but may involve a rise in inorganic phosphate. When severe ischemia,
      such as resulting from a sudden and complete coronary artery occlusion, is
      prolonged for more than 20-40 min, myocardial infarction develops, and there is
      irreversible loss of contractile function. When myocardial ischemia is less
      severe but nevertheless prolonged, the myocardium is dysfunctional but can remain
      viable. In such ischemic and dysfunctional myocardium, contractile function is
      reduced in proportion to the reduction in regional myocardial blood flow; i.e. a
      state of "perfusion-contraction matching" exists. The metabolic status of such
      myocardium improves over the first few hours, as myocardial lactate production is
      attenuated and creatine phosphate, after an initial reduction, returns towards
      control values. Ischemic myocardium, characterized by perfusion-contraction
      matching, metabolic recovery and lack of necrosis, has been termed "short-term
      hibernating myocardium". Short-term hibernating myocardium can respond to an
      inotropic stimulation with increased contractile function, however, at the
      expense of a renewed worsening of the metabolic status. This situation of an
      increased regional contractile function at the expense of metabolic recovery
      during inotropic stimulation can be used to identify short-term hibernating
      myocardium. When inotropic stimulation is prolonged, the development of short
      term hibernation is impaired and myocardial infarction develops. The mechanisms
      responsible for the development of short-term myocardial hibernation remain
      unclear at present; a significant involvement of adenosine and of activation of
      ATP-dependent potassium channels has been excluded. Whereas short-term
      hibernation is well characterized in animal experiments, the existence of
      hibernation over weeks or months (long-term hibernation) can only be inferred
      from clinical studies. Hibernation, as defined by Rahimtoola, is a state of
      chronic contractile dysfunction which is fully reversible upon reperfusion.
      Clinical syndromes consistent with the existence of myocardial hibernation
      include unstable and stable angina, acute myocardial infarction and left
      ventricular dysfunction and/or congestive heart failure. In long-term hibernating
      myocardium morphological alterations occur; the myofibrils are reduced in number
      and disorganized and myocardial glycogen content as well as the extracellular
      collagen network are increased. Thus, despite the fact that the myocardium
      remains viable during persistent ischemia and contractile dysfunction is
      reversible upon reperfusion, there are severe morphological alterations.
      Understandably, full functional recovery following reperfusion might therefore
      require weeks or even months.

PMID- 9004152
TI  - Adenovirus-mediated gene transfer of a heat shock protein 70 (hsp 70i) protects
      against simulated ischemia.
AB  - We have recently shown that the overexpression of a heat shock protein 70 (hsp
      70) in a rat myogenic cell line confers protection against simulated ischemia. We
      also developed and demonstrated that overexpression of this protein, in the
      hearts of transgenic mice, protects against ischemia/reperfusion injury. We have
      now inserted the hsp70 gene in an adenoviral vector and show that we are able to
      transfer and achieve overexpression of this protein in neonatal cardiomyocytes
      and in the rat myogenic cell line H9c2. We find that cells infected with the
      adenoviral-hsp70i construct are rendered tolerant to simulated ischemia as
      compared to cells infected with a control recombinant adenoviral construct. In
      conclusion, our results demonstrate the feasibility of using adenoviral vectors
      to overexpress the hsp70 in myogenic cells, specially in cardiomyocytes, and the
      efficiency of this approach for providing protection against myocardial ischemia.

PMID- 9004151
TI  - Differential protection of primary rat cardiocytes by transfection of specific
      heat stress proteins.
AB  - The aim of this study was to examine the individual contribution of specific heat
      stress proteins in primary rat cardiocytes to any protection observed following
      lethal heat stress or simulated lethal ischaemia. cDNAs for the inducible heat
      stress protein 70, for heat stress proteins 90 or 60, or a control plasmid were
      contransfected with a detectable marker, alkaline phosphatase, into cardiocytes.
      Survival assays were performed after the lethal stress. Transfection of the
      inducible heat stress protein 70 was found to increase survival following a
      lethal heat stress by 2.45-fold (P < 0.01) and against lethal ischaemia by 2.71
      fold (P < 0.01). Transfection of heat stress protein 90 improved survival against
      heat by 2.55-fold (P < 0.05) but failed to have any effect on survival against
      lethal ischaemia. Transfection of heat stress protein 60 offered no protection
      against either stress.

PMID- 9004154
TI  - Metabolic and functional consequences of successive no-flow and sustained low
      flow ischaemia; a 31P MRS study in rat hearts.
AB  - Recently, a model of acute hibernation, based on successive no-flow and low-flow
      ischaemia in the isolated rabbit heart has been described. In the present study
      this model was used in isolated rat hearts. 31P NMR was used to follow the time
      course of intracellular pH (pHi) and high-energy phosphates; mechanical activity
      of the heart was assessed simultaneously. Control hearts were subjected to 180
      min of low-flow ischaemia and 60 min of reperfusion (group A). In the acute
      hibernation group, low-flow was preceded by 5 min of no-flow ischaemia (group B).
      In group A contracture developed during low-flow. The time to onset of
      contracture was 51 min (range: 28 to 123 min). In group B, contracture did not
      occur during low-flow ischaemia (P < 0.01): recovery of left ventricular
      developed pressure and end-diastolic pressure was significantly better during the
      first 15 min of reperfusion (P < 0.05). In group A pHi decreased from 7.06 +/-
      0.04 to 6.64 +/- 0.14 during the first 30 min of low-flow. After contracture
      developed in this group two pHi values were measured amounting to 6.33 +/- 0.15
      and 6.86 +/- 0.05 at the end of low-flow. At the end of reperfusion pHi was 6.29
      +/- 0.05 and 7.09 +/- 0.06. In group B, pHi decreased from 7.08 +/- 0.03 to 6.55
      +/- 0.03 during no-flow ischaemia. During low-flow ischaemia, pHi increased to
      6.73 +/- 0.05 and remained constant. During reperfusion pHi recovered to 7.06 +/-
      0.03. In group A and B phosphocreatine (PCr) levels at the end of low-flow
      ischaemia amounted to 13 +/- 8% and 26 +/- 6% of pre-ischaemic levels,
      respectively. During reperfusion, PCr recovery was better in group B: 67 +/- 12%
      v 23 +/- 11% (P < 0.05). In group A and B, ATP levels at the end of low-flow
      ischaemia were 5 +/- 10% and 19 +/- 9%, respectively. The rate of ATP depletion
      during low-flow ischaemia was initially similar in both groups, but between 45
      and 90 min ATP depletion still continued in group A, while this had leveled off
      in group B (P < 0.01). During reperfusion no significant changes in ATP were
      observed. We propose that increased glucose transport and glycolytic flux are
      able to maintain ionic homeostasis and diastolic function when low-flow ischaemia
      is preceded by a short period of no-flow ischaemia.

PMID- 9004155
TI  - Heat shock protein changes in hibernation: a similarity with heart failure?
AB  - Myocardial hibernation is an adaptive phenomenon occurring during ischaemia.
      Patients with hibernating myocardium often have a history of an acute ischaemic
      insult, followed by prolonged hypoperfusion and symptoms of congestive heart
      failure (CHF), which is a complex syndrome involving several adaptational
      mechanisms. We tested the hypothesis that these two conditions evoke the
      myocardial expression of heat shock protein 72 (hsp72) as an adaptive response at
      the molecular level. Short-term acute hibernation was induced in isolated and
      perfused rat hearts subjected to 8 min total ischaemia followed by 292 min low
      flow ischaemia (coronary flow: 1.0 ml/min), followed by 60 min of reperfusion.
      Total ischaemia caused quiescience. Subsequent low-flow resulted in a temporal
      early increase of lactate release, no re-establishment of developed pressure, no
      increase in diastolic pressure. Reperfusion resulted in 85.7 +/- 7.2% recovery of
      developed pressure, a small washout of lactate and CPK, no contracture,
      confirming that viability was maintained despite prolonged hypoperfusion. This
      sequence of events was linked to an increase in hsp72 content in the right (from
      18.1 +/- 3.8% to 34.6 +/- 2.3%. P < 0.01) and left (from 19.7 +/- 2.6% to 37.6 +/
      3.3%, P < 0.01) ventricles. Three-hundred min of low-flow perfusion of the rat
      heart in absence of the short period of total ischaemia caused irreversible
      damage and failed to induced hsp72. CHF was induced in rats by intraperitoneal
      administration of monocrotaline. As a result, right ventricular weight increased
      from 171.3 +/- 7.2 to 412.3 +/- 18.7 mg. P < 0.001, peripheral and pleural
      effusion were evident and measurable, plasma arterial natriuretic peptide
      increased from 15.2 +/- 1.9 to 123.5 +/- 5.4 pg/ml, P < 0.001, confirming the
      occurrence of the syndrome of CHF. This was concomitant with significant
      expression of hsp72, more evident in the right (from 5.0 +/- 0.9% to 39.4 +/-
      1.6%, P < 0.001) than in the left (from 3.5 +/- 0.6% to 13.0 +/- 1.2%, P < 0.001)
      ventricle. These data suggest that an adaptational process occurs at myocardial
      level during either hibernation or CHF. The expression of hsp72 could be viewed
      as a stereotyped adaptational reaction of the cardiac cell to stress conditions.

PMID- 9004156
TI  - Clinical aspects of hibernating myocardium.
AB  - Hibernating myocardium is a condition that is characterized by persistently
      impaired myocardial and left ventricular function at rest resulting from reduced
      myocardial blood flow. It is a result of adaptation or from downregulation. It
      may occur in unstable and chronic stable angina, acute myocardial infarction, and
      LV dysfunction and congestive heart failure. Recovery of the hibernating
      myocardium has clearly been shown to occur by successful revascularization either
      by coronary bypass surgery or by percutaneous catheter techniques.

PMID- 9004157
TI  - The multifarious spectrum of ischemic left ventricular dysfunction: relevance of
      new ischemic syndromes.
AB  - Ischemic heart disease, once limited to a number of well defined entities such as
      angina of effort, unstable angina, and myocardial infarction, must now be
      regarded as a much more complex and elusive entity. Silent ischemia was the first
      of the new ischemic syndromes to be described. Recently, three further new
      syndromes have been added, namely stunning, hibernation and preconditioning. All
      three have one common theme--they can be related to ischemia and reperfusion. In
      stunning, there is post-reperfusion mechanical dysfunction that recovers. In
      hibernation, there is prominent contractile dysfunction, apparently out of
      proportion to the reduction in coronary flow, and the recovery upon reperfusion
      is good. In preconditioning, severe ischemia followed by reperfusion protects
      against subsequent ischemia which may modify the severity of ischemic damage in
      the other ischemic syndromes. Ischemic LV dysfunction as found in post-infarct
      patients and in the absence of any simple relation to reperfusion, can be either
      diastolic or systolic or both in nature. In ischemic LV diastolic dysfunction
      without major systolic dysfunction, calcium antagonists may be appropriate
      therapy which could point to a role for abnormalities in the regulation of
      cytosolic calcium. It is proposed that there is potentially a mixed post-infarct
      syndrome, which may comprise one or more of the new ischemic syndromes (silent
      ischemia, stunning, hibernation, and preconditioning), as well as a varying
      degree of systolic and/or diastolic dysfunction. The basis of the systolic
      dysfunction is, at least in part, post-infarct LV remodeling. Several of these
      entities could overlap in the same patient. The term "mixed post-infarct ischemic
      syndrome" is suggested to describe this condition.

PMID- 9004158
TI  - Improvement of hibernation in the clinical setting.

PMID- 9004159
TI  - Identification and characterization of G protein-regulated phospholipase C in
      human myocardium.
AB  - The generation of the second messengers inositol 1,4,5-trisphosphate (InsP3) and
      diacylglycerol (DAG) by phosphoinositide-specific phospholipases C (PLCs) is a
      key mechanism by which many cellular functions such as intracellular calcium
      handling or growth and differentiation are modulated. In the myocardium, PLC
      plays a role in the mediation of positive inotropic effects and is possibly
      involved in the pathogenesis of myocardial hypertrophy. Among the variety of PLC
      isozymes known, the PLC beta family is regulated by heterotrimeric G proteins.
      The aim of the present study was to identify and to characterize the PLC beta
      isoform present in human myocardium. PLC activity in human myocardial membranes
      was dependent on the presence of Ca2+. Interestingly, PLC was markedly stimulated
      by GTP gamma S, used as an activator of G proteins. This stimulation was
      completely abolished by GDP. However, purified alpha-subunits from retinal
      transducin (alpha 1), used as scavengers of free beta gamma-subunits, did not
      abolish this effect indicating GTP gamma S stimulation being mediated by G
      protein alpha-subunits. PLC activity was also stimulated by G protein beta gamma
      subunits purified from bovine retina (beta gamma t). This stimulation was
      completely blocked by addition of purified alpha t. Reverse transcriptions and
      polymerase chain reactions (RT-PCR) provided evidence for PLC beta 1 mRNA being
      expressed in human myocardium, whereas PCR products corresponding to PLC beta 2
      and PLC beta 3 mRNAs were not detected. It is concluded that PLC beta 1 mRNA is
      expressed in human myocardium. The functional properties of human myocardial PLC
      activity correspond well to the properties established for PLC beta 1, i.e.
      sensitivity to G protein alpha-as well as beta gamma-subunits. The presence of
      other as yet unidentified PLC isozymes is nevertheless possible. The
      identification of the PLC beta isozyme present in human myocardium and the
      understanding of its regulation by G protein subunits sets the stage for the
      investigation of possible involvement of this system in the pathophysiology of
      myocardial hypertrophy.

PMID- 9004160
TI  - Serum from patients with chronic renal insufficiency alters growth
      characteristics and ANP mRNA expression of adult rat cardiac myocytes.
AB  - Left ventricular hypertrophy is very prevalent among patients with renal
      insufficiency. Known hypertrophic factors, such as systemic hypertension, do not
      adequately account for the prevalence of left ventricular hypertrophy in these
      patients. Circulating growth factors may stimulate cardiomyocyte growth and
      contribute to the development of left ventricular hypertrophy. The effects of
      sera from patients with (n = 30) and without (n = 5) chronic renal insufficiency
      on the growth of cultured adult cardiomyocytes were compared. An adult rat
      cardiomyocyte primary culture system was established with a high purity of
      cardiomyocyte population as confirmed by immunocytochemical staining of cardiac
      contractile proteins. Myocytes responded with increased [3H]thymidine
      incorporation when treated with angiotensin II, epidermal growth factor,
      hydrocortisone and insulin, and with increased [3H]phenylalanine incorporation
      when treated with parathormone, isoproterenol, phenylephrine and insulin. Renal
      insufficiency serum stimulated [3H]thymidine incorporation was 1.5 times that of
      the control (P < 0.02) and also tended to increase incorporation of
      [3H]phenylalanine compared to the control (P = N.S.). Increased [3H]thymidine
      incorporation by renal insufficiency serum did not correlate with serum insulin,
      parathormone or glucose in the renal insufficiency patients. A quantitative
      reverse transcriptase polymerase chain reaction (RT-PCR) method was used to
      measure renal insufficiency serum-induced atrial natriuretic peptide mRNA
      expression in cultured cardiomyocytes. Atrial natriuretic peptide (ANP) mRNA was
      increased 1-3-fold in cardiomyocytes treated with renal insufficiency sera in
      comparison to control sera. These data suggest that circulating growth factor(s)
      may contribute to the development of cardiac hypertrophy in patients with renal
      insufficiency.

PMID- 9004161
TI  - Biphasic response of action potential duration to metabolic inhibition in rabbit
      and human ventricular myocytes: role of transient outward current and ATP
      regulated potassium current.
AB  - Inhibition of cell metabolism is associated with significant changes in action
      potential duration. The aim of this study was to investigate the time course of
      the changes in action potential duration during metabolic inhibition and to
      determine what changes in membrane currents are responsible. The amphotericin
      perforated patch clamp technique was used to study membrane currents and voltage
      in single rabbit and human ventricular myocytes. In all myocytes inhibition of
      cell metabolism, induced by hypoxia (PO2 < 5 mmHg) or by addition of 100 microM
      2,4-dinitrophenol (DNP), resulted in action potential shortening, which was
      accompanied by an increase in outward current, likely to be carried by ATP
      regulated potassium channels. In about 65% of the rabbit and 50% of the human
      ventricular myocytes, however, action potential shortening was preceded by an
      initial prolongation. During this action potential prolongation, the L-type
      calcium current and the steady-state outward current remained unchanged. The
      transient outward current (Ito), however, was almost completely inhibited,
      suggesting that the action potential prolongation is caused by a decreased Ito.
      This interpretation was further supported by the observations that: (1) Action
      potential prolongation was found in all subepicardial myocytes, as was Ito, but
      only in a minority of the subendocardial myocytes. (2) Addition of DNP failed to
      cause action potential prolongation in subepicardial myocytes in the presence of
      4-aminopyridine, a blocker of Ito. In conclusion, these data suggest that the
      phenomenon of action potential prolongation preceding action potential shortening
      during metabolic inhibition is mainly restricted to myocytes from subepicardial
      origin, and is due to a decrease in Ito.

PMID- 9004163
TI  - Phorbol myristate acetate-induced hypertrophy of neonatal rat cardiac myocytes is
      associated with decreased sarcoplasmic reticulum Ca2+ ATPase (SERCA2) gene
      expression and calcium reuptake.
AB  - The decreased expression of the sarcoplasmic reticulum Ca(2+)-ATPase associated
      with cardiac hypertrophy was investigated in cultured neonatal rat cardiac
      myocytes. Northern blot analysis indicated a significant 55-60% decrease in
      Ca(2+)-ATPase mRNA levels and after 12 and 24 h of treatment with the phorbol
      ester phorbol myristate acetate (PMA). Myocytes treated with the phorbol ester
      for 80 h showed a significant 34% decrease (relative to vehicle-treated control
      cells) in the levels of Ca(2+)-ATPase protein, and a significant 38% increase in
      the levels of alpha-sarcomeric actin, as assessed by Western blot analysis using
      specific antibodies. Immunocytochemistry of myocytes treated for 72 h with the
      phorbol ester revealed a hypertrophied cell morphology, and showed a marked
      decrease in Ca(2+)-ATPase staining intensity. Contractile calcium transients were
      evaluated through the use of indo-1. It was found that the t1/2 for the decline
      of calcium transient was significantly prolonged by PMA treatment (0.51 +/- 0.15)
      when compared to controls (0.38 +/- 0.17, P < 0.001). Treatment of myocytes with
      endothelin-1 also led to a 35% decrease in sarcoplasmic reticulum Ca(2+)-ATPase
      mRNA levels. It is concluded that phorbol ester treatment of neonatal rat cardiac
      myocytes induces similar changes in Ca(2+)-ATPase mRNA levels. It is concluded
      that phorbol ester treatment of neonatal rat cardiac myocytes induces similar
      changes in Ca(2+)-ATPase gene expression as observed in vivo in the hypertrophied
      and failing heart. The observed prolongation in t1/2 for [Ca2+]i decline might be
      due to the observed depressed levels for sarcoplasmic reticulum Ca(2+)-ATPase in
      PMA treated cells.

PMID- 9004162
TI  - Effects of IL-2 on the myocardium. Participation of the sympathetic system.
AB  - IL-2 is known to have various effects outside the frame of the immune system and
      it could have a role as an autocrine modulatory agent in certain cardiac
      dysfunctions associated to inflammatory cell infiltration of the heart. In this
      study, by means of binding assays on cardiac membranes or by evaluating
      contractility and cAMP levels of isolated rat atria in the presence of IL-2, we
      demonstrate that IL-2 may indirectly stimulate beta-adrenergic-mediated function
      by triggering the presynaptic release of norepinephrine (NE) on isolated rat
      atria. Thus it reacts with cardiac tissue inducing a positive inotropic response
      that can be blocked by the beta-adrenergic antagonist propranolol but not by
      phentolamine. Binding of the beta-adrenergic antagonist CGP 12177 is not affected
      by IL-2. Furthermore, chemical sympathectomy with 6-hydroxydopamine (6-OHDA)
      prevents the inotropic effect of IL-2, while cocaine treatment sensitizes atria
      to IL-2, indicating that NE secretion is required, and that the beta-adrenergic
      effect of IL-2 is presynaptic. In addition, IL-2 mimics beta-adrenergic
      stimulation increasing cAMP synthesis. Colchicine inhibited cAMP stimulation as
      well as positive inotropism, and both effects of IL-2 were additive with
      isoproterenol. However, cAMP synthesis could only be partially blocked by
      propranolol, suggesting that IL-2 stimulated cAMP synthesis both by a direct,
      beta-adrenergic independent mechanism and by a beta-adrenergic dependent pathway.
      We conclude that IL-2 induces a positive inotropic response in isolated rat atria
      through two different pathways: an indirect activation of myocardial beta
      adrenergic receptors by releasing catecholamines and a direct action by
      increasing the production of the second messenger cAMP.

PMID- 9004164
TI  - Preconditioning in globally ischemic isolated rat hearts: effect on function and
      metabolic indices of myocardial damage.
AB  - We assessed the effects of ischemic preconditioning on heart recovery and
      metabolic indices of damage following global ischemia and reperfusion, in
      relationship to post-ischemic lactate release. Three groups of Langendorff rat
      hearts were studied: (1) A control group of 40 min global ischemia and 45 min
      reperfusion; (2) preconditioning by 5 min global ischemia and 15 min reperfusion
      prior to sustained ischemia and reperfusion; (3) Preconditioning by three
      episodes of brief ischemia-reperfusion prior to sustained ischemia. Repetitive
      episodes of brief ischemia-reperfusion were associated with increased reactive
      hyperemia, decreased release of purines and prostaglandin 6-keto F1 alpha, lower
      tissue glycogen but no change in lactate washout. After 40 min ischemia, release
      of lactate was 173 +/- 17, 196 +/- 6 and 149 +/- 9 mumol/g in groups 1, 2 and 3,
      respectively (P < 0.01, group 2 v group 3). Preconditioning had no effect on
      ischemic arrest but had divergent effects on the development and the magnitude of
      ischemic contracture: delay and attenuation in group 2 but enhanced onset in
      group 3. Preconditioning provided a dose-dependent protection from the increase
      in left ventricular end-diastolic pressure, reduced the reperfusion release of
      purine metabolites and of creatine kinase, but neither improved systolic function
      nor prevented arrhythmia. 6-Keto F1 alpha production was 87 +/- 13, 132 +/- 19
      and 241 +/- 35 pmol/g in groups 1, 2, 3, respectively (P < 0.01 group 1 v group
      3). We conclude that when subjected to prolonged global ischemia, preconditioned
      isolated rat hearts develop less post-ischemic contracture, lose less purine
      nucleosides and creatine kinase activity. In addition, preconditioning leads to
      increased production of prostacyclin. Differences among preconditioning protocols
      in lactate production seem to be related to the ischemic contracture development,
      but may not play an ultimate role in attenuation of myocardial damage or
      improvement of postischemic recovery.

PMID- 9004166
TI  - Dystrophin-glycoprotein complex purified from hamster cardiac muscle. Comparison
      of the complexes from cardiac and skeletal muscles of hamster and rabbit.
AB  - The dystrophin-glycoprotein complex was isolated from hamster ventricular muscle
      by a method involving homogenization of muscle directly in the presence of 1%
      digitonin, followed by chromatography on succinylated wheat germ agglutinin
      agarose, Diethyl aminoethyl (DEAE) cellulose, and/or immunoaffinity agarose.
      Protein yield of the DEAE cellulose-purified dystrophin-glycoprotein complex was
      120 +/- 30 (n = 3) micrograms per 5 g hamster ventricular muscle. The cardiac
      dystrophin-glycoprotein complex, unlike the skeletal muscle counterpart, could
      not be solubilized from a microsomal fraction with digitonin or some other
      detergents. By sodium dodecyl sulfate gel electrophoresis, protein composition of
      the dystrophin-glycoprotein complexes from hamster cardiac muscle was found to be
      significantly different from that of rabbit skeletal muscle which has been
      extensively studied. This difference mainly arises from the species difference,
      because in hamster the cardiac and skeletal muscle complexes exhibited
      essentially the same protein composition. In rabbit, on the other hand, there are
      differences between the cardiac and skeletal complexes in the relative abundance
      of 60 and 64 kDa proteins and in the apparent M(r) of alpha-dystroglycan. We
      found that the content of the dystrophin-glycoprotein complex, estimated by
      quantitative immunoblot assay, is at least 5 times more abundant in cardiac than
      in skeletal muscle in hamster and rabbit.

PMID- 9004165
TI  - Differential modulation of cytokine production by drugs: implications for therapy
      in heart failure.
AB  - We studied the effects of various phosphodiesterase (PDE) III inhibitors:
      amrinone, pimobendan and vesnarinone: a PDE IV inhibitor (Ro 20-1724) and a PDE V
      inhibitor (E-4021) on the production of cytokines which have been shown to
      depress myocardial function. Recently developed inotropic agents which inhibit
      PDE III activity have produced short-term hemodynamic benefits in patients with
      advanced heart failure, but long-term treatment with these agents has an adverse
      effect on survival. However, vesnarinone, which has been shown to improve
      survival dramatically, has an immunomodulating effect and inhibits the production
      of cytokines. Peripheral blood mononuclear cells obtained from healthy human
      subjects were stimulated with lipopolysaccharide and each PDE inhibitor was
      added. After 24 h of incubation, tumor necrosis factor alpha (TNF-alpha),
      interleukin 1 beta (IL-1 beta) and IL-6 in the culture supernatants were measured
      by an enzyme-linked immunosorbent assay. All three PDE III inhibitors, amrinone,
      pimobendan and vesnarinone, inhibited TNF-alpha production, but vesnarinone's
      inhibitory effect was the most prominent. Amrinone and pimobendan enhanced IL-1
      beta production, whereas vesnarinone had no effect. Vesnarinone inhibited IL-6
      production and pimobendan slightly decreased IL-6 production, whereas amrinone
      had no significant effect on IL-6 production. The PDE IV inhibitor, Ro 20-1724,
      decreased the production of IL-1 beta and TNF-alpha and also tended to inhibit IL
      6 production; its modulation of cytokine production was similar to the effects of
      vesnarinone. Because 8Br-cAMP or 8Br-cGMP did not suppress cytokine production,
      the modulating effects were not considered to result from an increase in cAMP or
      cGMP. Differential modulation of cytokine production may play a role in the
      therapeutic effect in heart failure patients who are treated with drugs that have
      PDE-inhibitory actions. It may be important to study whether the use of dual
      inhibitors of PDE III and PDE IV is therapeutically more useful for the treatment
      of heart failure due to their immunomodulating properties.

PMID- 9004167
TI  - Action potential and plateau ionic currents in moderately and severely DOCA-salt
      hypertrophied rat hearts.
AB  - Ventricular hypertrophy is associated with an increase in action potential (AP)
      plateau amplitude and duration. In a model of cardiac hypertrophy by DOCA-pellet
      implantation in uninephrectomized saline-drinking rats, we have previously
      demonstrated that the influence of hypertrophy was to reduce Ito1 density, the
      process being fully reversible after elimination of DOCA pellets. In that study
      the decrease of Ito1 density appeared to vary from moderate reduction to complete
      suppression which could explain, at least in part, the AP lengthening. In the
      present study the effect of the degree of hypertrophy (moderate and severe
      hypertrophy) was investigated on rat ventricular action potential plateau
      amplitude and duration, high threshold calcium current, Ica-L, Na-Ca exchange
      current, INa-Ca, transient outward potassium current, Ito1, and sustained outward
      potassium current Isus. Ventricular action potentials of isolated perfused hearts
      were recorded by means of standard floating microelectrodes and ionic currents of
      single ventricular myocytes were measured using the whole-cell recording patch
      clamp technique. We show that: (1) AP plateau amplitude and duration increase
      more markedly in severe than in moderate hypertrophy; (2) the decrease in Ito1
      density is much larger in severe than in moderate hypertrophy whereas ICa-L, INa
      Ca and i(sus) densities remain unaltered in either state of hypertrophy. After
      suppression of Ito1 by 3 mM 4-aminopyridine, action potential plateau amplitude
      and duration remain increased in severely hypertrophied rat hearts compared to
      sham rats. Therefore, although these results designate Ito1 reduction as the main
      cause of hypertrophy-induced AP changes, those occurring in severe hypertrophy
      cannot be uniquely explained by a quasi-complete extinction of Ito1.

PMID- 9004168
TI  - Characterization of a hyperpolarization-activated inward current in cultured
      pacemaker cells from the sinoatrial node.
AB  - The perforated-patch, whole-cell voltage-clamp technique was used to characterize
      a hyperpolarization-activated inward current (if) in cultured pacemaker cells
      isolated from the rabbit sinoatrial (S-A) node. A modified Tyrode solution was
      used to block interfering currents. After correcting for uncompensated series
      resistance, leakage current and liquid-junction potentials between the pipette
      and bath, we obtained the following values for the maximum conductance and
      reversal potential of (i(f)): 16.2 +/- 2.8 nS or 0.26 +/- 0.07 nS/pF (0.37 +/-
      0.10 mS/cm2); and -27.7 +/- 1.2 mV (n = 10). In the modified Tyrode solution, the
      threshold for activation of i(f) and the half-activation potential and slope
      factor for Boltzmann fits were -66 +/- 1 mV (n = 53), -77.2 +/- 2.0 mV and 4.2 +/
      0.4 mV (n = 16), respectively. The time course of i(f) was best fit by a sum of
      two exponentials. Between -110 and -5 mV, time constants ranged from 0.06 to 0.42
      s for the rapid component and from 0.65 to 4.39 s for the slow component. Using
      these characteristics of i(f) and a short segment of spontaneous firing as the
      membrane potential, we computed the expected time course of i(f) during normal
      pacemaker activity. It reached a maximum of -3 pA during the diastolic
      depolarization and +4 pA during the action potential. We conclude that most of
      the characteristics of i(f) in cultured S-A node cells are similar to those
      measured previously in freshly isolated pacemaker cells.

PMID- 9004169
TI  - Changes in myofibrillar protein composition of human diaphragm elicited by
      congestive heart failure.
AB  - We describe the changes in proportions of myofibrillar proteins elicited by
      chronic congestive heart failure in the costal diaphragm (DIA) of humans using
      one and two-dimensional electrophoretic techniques. Three myosin heavy chain
      (MHC) isoforms were found in the DIA from control subjects: slow MHC I (43 +/-
      S.E. 2%), fast MHC IIa (41 +/- 2%) and fast MHC IIb (17 +/- 1%). In heart failure
      DIA, the percentage of MHC I was increased to 57 +/- 2%, while that of MHC IIb
      was decreased to 8 +/- 2 (P < 0.001 for both cases). Similarly, this DIA had
      higher molar ratios (%) of the slow myosin light chain isoforms (i.e. 1sa, 1sb,
      and 2s), and lower molar ratios of the fast isoforms (i.e. 1f, 2f, and 3f) than
      control DIA. Heart failure DIA also contained lower proportions of both alpha
      tropomyosin and fast isoforms of troponin-T, I and C than control DIA. These
      results indicate that heart failure elicits fast-to-slow transformations of both
      myosin and regulatory proteins of human costal DIA. These changes can be viewed
      as an increase in slow-twitch characteristics of the DIA and differ from the
      adaptations elicited by heart failure in limb muscles.

PMID- 9004170
TI  - GH-IGF axis during catch up growth in small for gestational age (SGA) infants.
AB  - The hormonal profile in 47 small for gestational age (SGA) term newborns during
      their first year of life was studied. The newborns had a mean birth weight of
      2290 +/- 230 g and a length of 45.5 +/- 2.0 cm, and they were followed up every
      month. Serum IGF-I, IGF-II, and urinary growth hormone (u-GH) concentrations were
      measured at 3 days of age and every 3 months during one year. Serum IGFBP-3
      levels were measured at 3 and 6 months of age. Catch up growth (CUG) was defined
      as an increase in length z score greater than 1 SD between birth and 6 months of
      age. According to this definition, 27 infants (57.4%) experienced CUG. We
      compared the hormonal profile of the infants who demonstrated evidence of CUG
      [CUG(+)] with those who did not [CUG(-)]. Serum IGF-II levels were significantly
      higher in CUG(+) infants compared to CUG(-) infants at 3 months of age. We did
      not find any differences in serum IGF-I, IGFBP-3 and urinary GH between CUG(+)
      and CUG(-) infants at any time during the study.

PMID- 9004172
TI  - GH secretion in Prader-Labhard-Willi syndrome: somatotrope responsiveness to GHRH
      is enhanced by arginine but not by pyridostigmine.
AB  - Low somatotrope responsiveness to secretagogues has been reported in patients
      affected by Prader-Labhard-Willi Syndrome (PLWS). In normal subjects, GH response
      to GHRH is known to be greatly potentiated to the same extent by pyridostigmine
      (PD) or arginine (ARG) which probably act via inhibition of hypothalamic
      somatostatin release. To clarify somatotrope responsiveness in 7 PLWS patients,
      we studied GH response to GHRH alone and to GHRH combined with PD or ARG. Eight
      normal short children were studied as controls (NC). GH response to GHRH in PLWS
      was lower than in NC (AUC: 615 +/- 205 micrograms/l.h, vs 1271 +/- 333
      micrograms/l.h, p < 0.02). In NC, the GHRH-induced GH rise was potentiated to the
      same extent by PD or ARG. In contrast, in PLWS PD failed to increase the GH
      response to GHRH (AUC: 615 +/- 205 micrograms/l.h vs 621 +/- 176 micrograms/l.h,
      n.s.) which was enhanced by ARG (AUC: 615 +/- 205 micrograms/l.h vs 1633 +/- 425
      micrograms/l.h, p < 0.02). However, the GH response to GHRH + ARG in PLWS was
      lower than in NC. In conclusion, our results demonstrate that in PLWS the low
      somatotrope responsiveness to GHRH is not enhanced by cholinergic potentiation
      while it is increased by arginine.

PMID- 9004171
TI  - Effect of glycemic control on the growth velocity and several metabolic
      parameters of conventionally treated children with insulin dependent diabetes
      mellitus.
AB  - To determine the effect of glycemic control on the growth velocity and several
      metabolic parameters of children with insulin-dependent diabetes mellitus (IDDM),
      79 patients with IDDM, 45 females and 34 males with a mean chronological age of
      8.4 +/- 3.0 years were followed over a 5-year period starting at the onset of
      diabetes. Glycemic control was assessed by measuring total glycosylated
      hemoglobin; children were divided into better controlled, GHb < 9%, 30 children
      (Group A) and worse controlled, GHb > or = 9%, 49 patients (Group B). Growth
      velocity was significantly lower, in the five years of follow up, in the worse
      controlled patients when compared to the better controlled subjects (4.8 +/- 1.6
      vs 6.7 +/- 2.2 cm/yr after the first year and 5.0 +/- 2.0 vs 6.5 +/- 1.8 cm/yr
      after the fifth year, in group B and group A, respectively). Higher cholesterol
      (185.3 +/- 33.7 vs 158.8 +/- 39.5 mg/dl) and triglyceride levels (85.9 +/- 43.5
      vs 71.0 +/- 37.4 mg/dl) were apparent in the worse controlled patients, when
      compared to the better controlled children. Insulin dose was not significantly
      different in the two groups (0.76 +/- 0.3 vs 0.84 +/- 0.4 U/kg/day in the 1st
      year and 0.9 +/- 0.3 vs 0.92 +/- 0.4 U/kg/day in the 5th year, in group B and A
      respectively). Although both groups received the same initial and long term
      training by our pediatric diabetes team, more frequent blood glucose monitoring,
      better record keeping and rotation of injection sites and more clinic visits were
      clearly noted in the better controlled group. Ketoacidotic episodes were more
      common in the worse controlled patients, while better controlled children had a
      higher number of hypoglycemic episodes. In conclusion, we have found poor
      glycemic control, as reflected by higher glycosylated hemoglobin levels, to
      affect the growth velocity and several metabolic parameters of children with
      diabetes followed for a five-year period. Other factors besides insulin dose and
      initial and subsequent diabetic education seem to play a role in their glycemic
      control.

PMID- 9004173
TI  - Insulin secretion decline unrelated to jejunal morphology or exocrine pancreatic
      function in children with celiac disease.
AB  - We describe a prospective 10-year study of insulin secretion and immunologic
      changes in a group of children with celiac disease (CD) on a gluten-free diet.
      Thirty CD patients aged 4-16 years and 30 matched controls were examined. They
      underwent i.v. glucose tolerance test during which glucose disappearance rate (K)
      and first phase insulin response (FPIR) were measured. Typing for HLA A, B, C,
      and DR antigens was performed and sera were analyzed for cytoplasmic islet cell
      antibodies (ICA) on several occasions. Pancreatic isoamylase (PIA) was measured
      to assess exocrine pancreatic function. In 4/21 CD children, FPIR and K rate were
      decreased. There was a significant correlation between the two parameters (p <
      0.01). The incidence of HLA B8 and DR3 was higher in CD (33% and 60%,
      respectively) than in healthy individuals (p < 0.001). All patients were found to
      be ICA negative at the time of the study and at follow-up. There was no
      correlation between parameters of endocrine (FPIR, K) and exocrine (PIA)
      pancreatic function. One out of four children with reduced FPIR developed overt
      DM during the study. In conclusion, the decline of first phase insulin secretion
      documented in CD patients is unrelated to jejunal morphology or exocrine
      pancreatic function. This decline may be an expression of a prediabetic phase as
      observed in one of the subjects who finally developed IDDM. HLA B8 and DR3, which
      are detected in celiac patients, may indicate a possible common pathogenic
      mechanism between CD and IDDM.

PMID- 9004174
TI  - Hypophosphatemia induced in mice by transplantation of a tumor-derived cell line
      from a patient with oncogenic rickets.
AB  - A cultured cell line was derived from a hemangiopericytoma obtained at surgery
      from a 9 year-old boy with hypophosphatemic rickets. Hypophosphatemia and
      metabolic bone disease were cured in the patient after tumor removal. Cells from
      passage 5 were transplanted into 8 week-old athymic female mice. Additional
      animals received innocula of cells thawed from the stored original tumor tissue,
      as well as MRC-5 fibroblasts. Serum phosphate levels 3-7 months post
      transplantation were lowest in mice which received the cultured cell line (n = 5)
      6.1 +/- 0.6 mg/dl (p < 0.05 compared to the other groups), thawed tumor cells (n
      = 8) 7.2 +/- 0.7 mg/dl, MRC fibroblasts (n = 4) 8.1 +/- 1.0 mg/dl, no transplant
      (n = 10) 8.7 +/- 1.9 mg/dl. Repeat of the experiment with cultured tumor cells
      from passage 12 no longer altered phosphate levels. A substance produced and
      release by the tumor in situ and by tumor-derived cultured cells is capable of
      producing hypophosphatemia. Experimental manipulation of functional tumor-derived
      cell lines may help elucidate the factor(s) causing hypophosphatemia in oncogenic
      osteomalacia/rickets.

PMID- 9004175
TI  - Two types of growth hormone rhythm in boys with constitutional short stature.
AB  - The relationship between temporal and quantitative changes in pulsatile growth
      hormone (GH) secretion and growth of constitutionally short children (CSS) was
      studied in 19 prepubertal boys and 4 with early adrenarche aged 7.8 to 14 years.
      Continuous plasma GH monitoring was performed at 30 minutes intervals during 24
      hours. The data were analysed by single and serial best fit (BFT) cosinor
      analysis for rhythm parameters and the Pulsar peak detection program for
      determining pulsatile properties. The pulsatile patterns were expressed in mean
      GH concentration, area under the curve, mean pulse area and maximal pulse height
      but not in the number of pulses. Thirteen out of 23 patterns exhibited
      significant 24-h compatible rhythms. The studied cohort was divided into two
      groups, those who exhibited the 24-h circadian rhythm (CIR) and those who lacked
      it (NCIR). Ultradian 2.5-4 h rhythms were observed in all patients. The NCIR
      children were significantly shorter than the CIR group (p = 0.017). The CIR boys
      secreted a significantly higher (p = 0.01) amount of GH during the 24-h span,
      most of which was during sleep. Our data indicate that the magnitude of pulses
      rather than their number is responsible for the quantitative differences observed
      between the two groups of boys with CSS. It is suggested that a lack of 24-h
      rhythmicity and the associated reduced nocturnal pulsatility play a role in the
      manifestation of short stature.

PMID- 9004176
TI  - The correlation of serum ferritin level to Ca-P metabolism and bone density study
      in thalassemic patients.
AB  - A study of Ca-P related hormones and bone densities was carried out in seven
      homozygous beta-thalassemia patients. The levels of Ca, P, and Ca-P related
      hormones were not significantly changed except for 1,25(OH)2D3 which was
      significantly lower than in the control group and was inversely related to
      patients' ferritin levels. Bone densities were markedly reduced in all the
      thalassemic patients.

PMID- 9004178
TI  - Macrotestes associated with hyperprolactinemia.
AB  - Prolactin secreting pituitary adenomas are a rare finding in prepubertal children
      /1/. As in adults, their incidence is higher in girls than in boys; however, the
      macroadenomas are predominant in boys /20-16/. Two prepubertal boys who presented
      with short stature and linear growth deceleration were diagnosed to have
      prolactin secreting pituitary macroadenoma associated with growth hormone (GH)
      deficiency. They were treated with bromocryptine and exogenous recombinant hGH.
      They achieved a normal adult stature, full sexual maturation and tumor regression
      on the therapy. In addition, both boys developed macrotestes. Further evaluation
      ruled out other etiologies for macrotestes. We presume that the elevated
      prolactin caused local testicular growth factors to induce testicular cell
      division and/or hypertrophy resulting in an increased testicular volume.

PMID- 9004177
TI  - Nodular hyperplasia in treated congenital goitrous hypothyroidism.
AB  - Two patients with congenital goitrous hypothyroidism, treated since birth, are
      described. Each developed progressive nodular thyroid enlargement in adolescence,
      possibly related to ongoing thyroid stimulation due to slight and transient
      elevations of thyroid stimulating hormone (TSH) levels. The incidence and degree
      of persistent thyroid enlargement in these patients has not been well documented.
      If present in a significant number of patients despite appropriate L-thyroxine
      replacement, our therapeutic aims in congenital goitrous hypothyroidism may need
      to be modified to achieve TSH suppression, rather than normalization.

PMID- 9004179
TI  - Development in a 46 XX boy with positive SRY gene.
AB  - We present the case of an 11 year-old boy, who asked for medical attention due to
      obesity and assumed underdeveloped external genitalia. He did not have genital
      anomalies, penile length was 5.3 cm, testicular volume 2 ml and pubic hair Tanner
      stage 1. His bone age was normal for chronological age. Endocrinological study
      showed normal results for his age. Karyotype revealed a 46 XX pattern. MRI of
      external genitalia showed bilateral scrotal testes which were normal in diameter
      for his age. The check of his historical growth chart and follow-up revealed
      normal growth with spontaneous pubertal development. However, hormonal studies
      showed progressive increase of FSH levels, indicative of failure of germinal
      epithelium. The presence of Y sequences, including SRY gene, was demonstrated by
      PCR. Our observation is in agreement with the view that 46 XX male subjects
      diagnosed at peripubertal age with the SRY gene in the genome have a good
      prognosis regarding growth and development, but the principal problem of these
      patients is infertility.

PMID- 9004181
TI  - QSAR studies of some sulphonamidobenzophenone oximes with antiviral activity.
AB  - A study of quantitative structure-activity relationships (QSAR) has been
      performed for some sulphonamidobenzophenone oximes to investigate the mechanism
      of their antiviral activity against polio and rhino viruses. It has been shown
      that viral macromolecule synthesis could be the target of their action and that
      the antiviral activity of the compounds is predominantly controlled by steric
      factors.

PMID- 9004180
TI  - Hyperglycemia and acute parotitis related to L-asparaginase therapy.
AB  - In a boy with non-Hodgkin's lymphoma (NHL), two different complications developed
      concurrently associated with L-asparaginase (L-ASP) therapy. A non-ketotic
      hyperglycemic state was observed simultaneously with bilateral acute parotitis
      after the patient was subjected to L-ASP. The hyperglycemia with normal insulin
      levels and the absence of plasma and urine ketones was controlled with insulin
      therapy and no residual impairment of glucose tolerance was demonstrated later.
      Bilateral acute parotitis, which is a rare complication associated with L-ASP,
      resolved spontaneously within a week after cessation of L-ASP. The rarely
      observed toxic effects of L-ASP, such as parotitis, should be recognized as
      promptly as the better-known complications, e.g., hyperglycemia, to avoid the
      continuation of this antineoplastic agent.

PMID- 9004182
TI  - Synthesis and inhibition of human leucocyte elastase by functionalized N-aryl
      azetidin-2-ones: effect of different substituents on the aromatic ring.
AB  - N-aryl-3,3-difluoroazetidin-2-ones featured by a latent electrophilic methylene
      quinoniminium function have been synthesized and evaluated as inhibitors of human
      leucocyte elastase. To promote hydrophobic interactions with the enzyme, to
      increase the rates of beta-lactam ring opening and of benzylic group departure,
      or to induce hydrosolubility, these compounds incorporate on their aromatic ring
      either an alkyl moiety, a methoxy substituent or a carboxylic group. Some of
      these beta-lactams proved to be good inactivators of human leucocyte elastase.

PMID- 9004183
TI  - Chemical and pharmacological studies of Phyllanthus caroliniensis in mice.
AB  - The aim of this study was to isolate and characterize the constituents of the
      hydroalcoholic extract (HE) of the leaves, stems and roots from P. caroliniensis,
      and also to evaluate the preliminary antinociceptive action of the HE and
      purified compounds in mice. Phytosterols, quercetin, gallic acid ethyl ester and
      geraniin were identified in P. caroliniensis on the basis of 1H and 13C NMR
      spectral data and by mixed co-TLC and co-HPLC injection with authentic samples.
      The HE of P. caroliniensis (10-100 mg kg-1, i.p.) inhibited, in a dose-related
      manner, acetic acid-induced abdominal constrictions in mice, with a mean ID50
      value of 23.7 mg kg-1. In the formalin test, the HE given intraperitoneally (1-30
      mg kg-1) or orally (25-600 mg kg-1) caused graded inhibitions of both the
      neurogenic (first phase) and the inflammatory response (late phase) of formalin
      induced licking. The HE was 54-fold more effective in inhibiting the late phase
      than it was in inhibiting the first phase of the formalin test, with mean ID50
      values of 3.6 and 196.4 mg kg-1, respectively. The HE failed, however, to affect
      the oedematogenic response associated with the late phase of formalin-induced
      pain. In addition, the reference drug, aspirin, given intraperitoneally (1-100 mg
      kg-1) or orally (100-600 mg kg-1), caused significant inhibition of the late but
      not the first phase of the formalin test. Pharmacological analysis also revealed
      that quercetin, gallic acid ethyl ester and a semi-purified fraction of
      flavonoids (1-100 mg kg-1, i.p.) exhibited graded and significant antinociception
      against acetic acid-induced abdominal constriction. The mean ID50 values (mg kg
      1) for these effects were: 18.8, 34.7 and 5.3, respectively. It is concluded that
      quercetin, gallic acid ethyl ester and some as yet unidentified flavonoids might
      account for the antinociceptive action reported for the HE of P. caroliniensis.

PMID- 9004184
TI  - Preservative efficacy tests in formulated nasal products: reproducibility and
      factors affecting preservative activity.
AB  - Preservative efficacy tests were performed in triplicate on each of three batches
      of three formulated nasal spray preparations to assess the inter- and intra-batch
      variation in preservative performance which typically results from these
      procedures, and to assess the relative importance of factors influencing
      preservative performance in nasal products. Tests were conducted using procedures
      conforming, as far as possible, to both the European and the US pharmacopoeias
      and the results interpreted using the performance criteria of both. Despite the
      adoption of practices designed to maximize reproducibility, a marked variation in
      the degree of microbial inactivation was observed, both within and between
      batches of product. A preservative system comprising benzalkonium chloride and
      phenylethyl alcohol was found to be far superior to combinations of either
      benzalkonium chloride plus disodium edetate or potassium sorbate plus disodium
      edetate, both of which failed to satisfy the EP performance criteria on a number
      of occasions. Proposals are made for the adoption of inactivation criteria which
      incorporate realistic error limits reflecting the inherent problems of
      reproducibility of the viable counting procedures involved.

PMID- 9004185
TI  - Immunopharmacological activity of the purified insoluble glucan, zymocel, in
      mice.
AB  - Although it has been established that soluble glucan in fungi is important to
      host defence against infection, the importance of insoluble glucans is not clear.
      We have examined the in-vivo immunopharmacological activity of the insoluble
      glucan, zymocel. Administration of zymocel increased peritoneal exudate cell
      number and spleen weight, and enhanced: phagocytic activity, hydrogen peroxide
      production, and nitric oxide production of peritoneal exudate cells; the
      extravascular release of Evans blue (which might reflect vascular permeability);
      lipopolysaccharide-triggered synthesis of tumour necrosis factor (TNF); and
      recovery of white blood cell number in cyclophosphamide-induced leukopenia.
      Zymocel also showed anti-tumour activity against sarcoma 180 in mice and also
      enhanced TNF synthesis and hydrogen peroxide production by macrophage-like cell
      line in-vitro, i.e. resulted in direct macrophage activation. These results show
      that zymocel shows varied immunopharmacological activity; it is suggested that
      the administration of insoluble glucan induces the inflammatory response, the
      subsequent activation of the immune systems via the cytokine network, and direct
      macrophage activation.

PMID- 9004186
TI  - Influence of the carrier on the intrinsic rate of dissolution of diazepam in
      interactive mixtures.
AB  - The use of interactive mixtures of drugs adhering to the surface of carriers can
      promote drug dissolution. The mechanism of dissolution of such mixtures has been
      studied using the rotating-disc method under conditions eliminating secondary
      influences such as carrier surface characteristics and drug particle aggregation.
      Levich plots were used to characterize the dissolution behaviour. Diazepam
      compactrol interactive mixtures had initial dissolution rates similar to that of
      pure diazepam owing to the deposition of a continuous layer of diazepam on the
      disc surface from the interactive mixture. Linear Levich plots were produced at
      all drug loadings and the presence of compactrol in the disc slightly enhanced
      dissolution rates. Dissolution rates for diazepam-emcompress interactive mixtures
      were lower than those of pure diazepam. The Levich plots for these systems were
      non-linear with increasing negative curvature as the diazepam loading decreased.
      The rate of dissolution of diazepam in the lactose interactive mixture was
      markedly higher than that of pure diazepam, but high diazepam loadings in the
      lactose mixtures inhibited diazepam dissolution. Rapid carrier dissolution caused
      surface retraction of the disc, enhancing the dissolution rate. The Levich plots
      showed an upward curvature due to turbulence. Linear Levich plots for diazepam
      and other benzodiazepines and for diazepam-compactrol interactive mixtures showed
      that their dissolution in pH 5 phosphate buffer was diffusion-controlled. The
      Levich plots for diazepam-emcompress interactive mixtures were indicative of some
      interfacial control during dissolution, but the hypothesis of common ion
      precipitation of dissolved carrier, calcium phosphate, onto the disc surface did
      not fully explain this effect.

PMID- 9004187
TI  - A pharmacokinetic study of sublingual aerosolized morphine in healthy volunteers.
AB  - A pharmacokinetic study was undertaken to compare the pharmacokinetics of
      morphine after an intravenous dose with the pharmacokinetics after a sublingual
      dose administered from an aerosol. Plasma levels of morphine, morphine-3
      glucuronide and morphine-6-glucuronide were measured in five normal volunteers
      after morphine administration by the intravenous route and from a novel
      sublingual pressurized aerosol formulation. The mean (+/- s.d.) bioavailability
      of the sublingual aerosol morphine was 19.7 +/- 6.7%. The morphine-3
      glucuronide/morphine and the morphine-6-glucuronide/morphine ratios were 5.1 +/-
      1.6 and 1.2 +/- 0.4, respectively, for the intravenous route and 28.3 +/- 11.3
      and 5.2 +/- 1.4, respectively, for the sublingual route. The combined total areas
      under the plots of systemic concentration against time (AUC) for the metabolites
      after the two routes was not significantly different. When compared with
      published data for oral administration the results demonstrate that the
      sublingual aerosol morphine might provide an alternative to conventional methods
      of morphine delivery, and has similar pharmacokinetics to a sublingual morphine
      tablet. It has no particular pharmacokinetic advantages over oral morphine,
      except a potential for a faster onset of analgesia. Bioavailability, maximum
      plasma concentration, Cpmax, and the time at which the maximum plasma
      concentration is reached, Tmax, are equivalent to those for orally administered
      morphine.

PMID- 9004188
TI  - Pharmacokinetic analysis of the absorption characteristics of diclofenac sodium
      in man by use of a multi-segment absorption model.
AB  - The pharmacokinetic analysis of an oral sustained-release preparation of
      diclofenac sodium has been investigated using multi-segment absorption models in
      which it has been assumed that the gastrointestinal tract can be divided into
      several segments in each of which the drug has its own lag-time and absorption
      rate constants. Plasma concentration-time data for sustained release diclofenac
      sodium in man were fitted both by a conventional pharmacokinetic method assuming
      first-order absorption and by a multi-segment absorption model. The plasma
      concentration of diclofenac sodium calculated on the basis of the multi-segment
      absorption model was found to correlate with the observed plasma concentration.
      It was concluded that diclofenac sodium data can be better described by a multi
      segment absorption model than by a conventional pharmacokinetic model. The
      results also show that multi-segment absorption models are suitable for
      pharmacokinetic analysis of plasma drug-concentration data with irregular or
      multiple peaks in the absorption profiles, and also for the pharmacokinetic
      analysis of sustained-release preparations.

PMID- 9004189
TI  - Pharmacokinetic-toxicodynamic relationships of adriamycin in rat: prediction of
      butylated hydroxyanisole-mediated reduction in anthracycline cardiotoxicity.
AB  - Adriamycin, an anthracycline antibiotic, has broad antitumour activity with
      cumulative dose-dependent cardiotoxicity as its major side effect. This study was
      designed to quantify and correlate the cardiotoxicity and pharmacokinetics of
      adriamycin in-vivo in rat. The influence of antioxidant (butylated
      hydroxyanisole, BHA) co-therapy on the cardiotoxicity and disposition of
      adriamycin was also studied. Cardiotoxicity was estimated by serially measuring
      serum creatine kinase (CK) levels after intravenous administration of adriamycin
      (4, 10, 20, and 30 mg kg-1) and adriamycin-BHA (10 and 30 mg kg-1 each). Peak
      serum CK concentrations (CKmax) and area under serum CK-time curves (AUCCK) were
      used as cardiotoxicity indices. Pharmacokinetic studies were undertaken by
      sampling plasma and urine from distinct groups of rats treated with
      [14C]adriamycin (at the above doses) and [14C]adriamycin-BHA (10 mg kg-1 each).
      Co-administration of BHA resulted in a significant reduction in CKmax and also
      resulted in a significant reduction in the renal clearance of adriamycin which
      was fully compensated by an increase in its metabolic clearance. A linear
      increase in the area under the plasma adriamycin concentration-time curves (AUC)
      with increasing adriamycin doses suggested dose-independent disposition of the
      drug. The most significant pharmacokinetic-toxicodynamic relationships included:
      CKmax = 2.25 x 10(2) exp (4 x 10(-4) AUC), r2 = 0.941, P < 0.05 and AUCCK = 1.3 x
      10(4) exp(2 x 10(-4) AUC0-tmax), r2 = 0.918, P < 0.05 where, AUC0-tmax is the
      area under the adriamycin concentration-time curve from time 0 to the time of the
      peak CK level. The results strongly indicate that the drug-induced cardiotoxicity
      is initiated shortly after dosing when drug concentrations are high and
      accumulates with continued exposure. The predicted cardiotoxic indices, obtained
      from altered adriamycin pharmacokinetic parameters as a result of BHA co-therapy,
      compared favourably with the observed values.

PMID- 9004191
TI  - Bioavailability and in-vitro/in-vivo correlation for propranolol hydrochloride
      extended-release bead products prepared using aqueous polymeric dispersions.
AB  - The influence of formulation and extrinsic factors has been investigated for the
      in-vitro release of propranolol hydrochloride from controlled-release beads
      prepared using aqueous polymeric dispersions, Aquacoat and Surelease. A single
      dose three-way crossover bioavailability study of two extended-release
      experimental formulations (80 mg), Inderal LA (80 mg) and an Inderal immediate
      release dosage form (2 x 40 mg) was also conducted and a comparative analysis of
      pharmacokinetic parameters and the in-vitro release profiles was performed to
      assess in-vitro/in-vivo correlation. Analysis showed that the in-vitro release
      data appeared to follow zero-order release kinetics. Intensity of agitation and
      dissolution method were found to have no significant effect on drug release from
      beads prepared using either of the coating dispersions studied or Inderal LA.
      Release of drug from beads coated with Aquacoat was faster in basic media than in
      acidic media; Surelease-coated beads, however, showed release characteristics
      that were less sensitive to changes in the pH of the dissolution fluid, and
      Inderal LA beads showed slower release profiles in acidic medium than in other
      dissolution media studied. Pharmacokinetic analysis of the data revealed
      sustained-release absorption characteristics without any evidence of dose-dumping
      from any of the extended-release dosage forms studied. Regression analysis of the
      fraction of drug absorbed against the percentage of the drug released in-vitro,
      at the corresponding times, yielded good in-vitro/in-vivo correlation (level A)
      for all the extended-release formulations studied. The results showed that there
      was no dose-dumping from any of extended-release formulations and that the
      relative bioavailabilities of the experimental formulations were superior to that
      of the marketed formulation.

PMID- 9004192
TI  - Effectiveness and toxicity screening of various absorption enhancers in the rat
      small intestine: effects of absorption enhancers on the intestinal absorption of
      phenol red and the release of protein and phospholipids from the intestinal
      membrane.
AB  - Sodium glycocholate, sodium taurocholate, sodium deoxycholate, EDTA, sodium
      salicylate, sodium caprate, diethyl maleate, N-lauryl-beta-D-maltopyranoside,
      linoleic acid polyoxyethylated (60 mol) mixed micelles (all 20 mM) have been
      ranked in order of their effectiveness as enhancers of the absorption of drugs in
      the rat small intestine, by use of an in-situ loop model with phenol red as a
      model drug. Local toxicity in rats was examined by assessing protein and
      phospholipid release as biological markers. Of the absorption enhancers, sodium
      deoxycholate, EDTA and N-lauryl-beta-D-maltopyranoside were the most effective;
      sodium deoxycholate and EDTA, however, caused significant release of protein and
      phospholipids. N-lauryl-beta-D-maltopyranoside, on the other hand, did not damage
      the small intestinal membrane. Sodium taurocholate enhanced phenol red absorption
      from the small intestine and resulted in little or no protein and phospholipids
      release. Sodium salicylate, diethyl maleate and the mixed micelles had no
      absorption-promoting effects on phenol red. There was good correlation between
      the area under the plasma concentration-time curve for phenol red and the amounts
      of protein and phospholipid released in the presence of absorption enhancers.
      From these results it might be concluded that N-lauryl-beta-D-maltopyranoside and
      sodium taurocholate are effective absorption enhancers which have low toxicity
      levels at a concentration of 20 mM.

PMID- 9004190
TI  - Pharmacokinetic study of zonisamide in patients undergoing brain surgery.
AB  - To test whether the concentration of the anticonvulsant zonisamide in
      erythrocytes reflects the brain concentration and the clinical response of the
      drug, its pharmacokinetics were studied in nine patients undergoing surgery for
      brain tumour. Erythrocyte, total and free serum concentrations in samples drawn
      on the day of brain surgery were compared with levels on a day after the
      operation. In three patients zonisamide and its major metabolite, 2
      sulphamoylacetylphenol, were also analysed in urine. The area under the curve of
      the free and the erythrocyte concentration did not differ between the two study
      phases whereas the area under the curve of the total serum concentration was
      significantly lower on the day of the operation, and this was associated with
      significant increases in total clearance (15.4 compared with 12.7 mL kg-1 h-1, P
      < 0.05, n = 9) and renal clearance (5.4 compared with 3.3 mL kg-1 h-1, P < 0.05,
      n = 3), and non-significant change in non-renal clearance (7.7 on the day of
      operation compared with 8.4 mL kg-1 h-1 on the post-operation day, n = 3).
      Zonisamide distribution was also altered by the operative procedure, as evidenced
      by a higher volume of distribution (1.48 compared with 0.87 L kg-1, P < 0.05, n =
      9). The binding of zonisamide was characterized on both days. Zonisamide binding
      to erythrocytes seemed to occur by two processes: a saturable process and a non
      saturable linear process. The maximum binding capacity to erythrocytes (31.6 vs
      29.7 micrograms mL-1) did not differ on the two days; however, increases in the
      dissociation binding constant (+28%) and the proportionality constant (+24%) were
      observed on the day of the operation, suggesting that the zonisamide
      concentration in erythrocytes was greater on the day of the operation. Brain
      surgery appears to be one of the possible factors altering the rate of
      elimination of zonisamide and the uptake of the drug by erythrocytes.

PMID- 9004193
TI  - CR 2249: a new putative memory enhancer. Behavioural studies on learning and
      memory in rats and mice.
AB  - The effects of S-4-amino-5-[4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid (CR
      2249), a new entity selected from a new series of glutamic acid derivatives, has
      been investigated in different paradigms for screening nootropics. CR 2249
      ameliorated the memory retention deficit produced by scopolamine in step-through
      type passive avoidance in rats and by electroconvulsive shock in step-down-type
      passive avoidance in mice. CR 2249 was also capable of improving performance in
      behavioural tests of learning and memory in the absence of cholinergic
      hypofunction or cognitive deficit. The activity was determined using different
      passive and active avoidance behavioural test procedures on rats. CR 2249 was
      active only when given 45 min before training and did not show any effect when
      administered immediately after the learning training or before the retention
      trial. No changes in the general behaviour or motor activity of the animals were
      observed, indicating that CR 2249 effects cannot be attributed to sensory-motor
      deficit. Microdialysis experiments have shown that CR 2249 significantly
      increased noradrenaline release in the hippocampus of freely moving rats and
      reduced 3,4-dihydroxyphenylglycol efflux. These effects have led us to
      hypothesize that CR 2249 memory effect might be mediated by a direct or indirect
      action on noradrenergic transmission. These behavioural results suggest that this
      new agent has clinical application in memory disorders.

PMID- 9004194
TI  - Characterization of alpha-adrenoceptor activity in term-newborn piglet mesentery.
AB  - For further characterization of neonatal mesenteric alpha 1-adrenoceptor
      populations, an extracorporeal perfusion circuit was established to control
      intestinal blood flow in 0-2 day old piglets. Activation of alpha 1-adrenoceptors
      was first documented by observing dose-dependent increases in mesenteric
      perfusion pressure after intra-mesenteric arterial injection of methoxamine and
      noradrenaline. Peripheral intravenous injections of WB 4101 (a competitive alpha
      1A-adrenoceptor antagonist), but not clorethylclonidine (CEC, an alpha 1B
      adrenoceptor antagonist), significantly (P < 0.05, analysis of variance) blunted
      mesenteric vasoconstrictor responses to those agonists. That the mesenteric
      vasoconstrictor response to mesenteric plexus stimulation was unaltered by CEC,
      but was muted by both WB 4101 and SK&F 104856 (a post-junctional alpha 1- and
      alpha 2-adrenoceptor antagonist) suggests that pre- and post-junctional alpha 1A
      adrenoceptors are present and functional at birth.

PMID- 9004195
TI  - Effects of 5-hydroxytryptamine agonists on myoelectric activity of the
      forestomach and antroduodenal area in sheep.
AB  - To increase knowledge of the role of 5-hydroxytryptamine (5-HT) receptors in the
      regulation of reticuloruminal, omasal and antroduodenal myoelectric activity in
      sheep, the effects of 5-HT agonists on forestomach and antroduodenal myoelectric
      activity have been investigated in conscious sheep. 5-Carboxamidotryptamine,
      methysergide, alpha-methyl-5-HT, 2-methyl-5-HT, cisapride, zacopride or
      metoclopramide were infused intravenously for 5 min and myoelectric recordings
      were obtained from electrodes chronically implanted in the reticulum, rumen
      (dorsal sac), omasal body, abomasal antrum and duodenal bulb. The integrated
      activity of the reticular and ruminal spike bursts was modified only by the
      highest doses of alpha-methyl-5-HT, 2-methyl-5-HT, metoclopramide and cisapride.
      A phase III-like activity pattern was recorded in the antroduodenal area with all
      5-HT-ergic agents and a dose-dependent inhibition of myoelectric activity was
      recorded in both reticulorumen and omasum at the same time as the antroduodenal
      effects. In the forestomach, methysergide alone induced inhibition of ruminal
      secondary contractions; 5-HT, alpha-methyl-5-HT, cisapride and metoclopramide,
      moreover, evoked an initial dose-dependent increase in antral activity. These
      results suggest that 5-HT1, 5-HT2, 5-HT3 and 5-HT4 receptors are involved in the
      regulation of the migrating myoelectric complex in sheep and in the genesis of
      forestomach hypomotility that is occasionally recorded concomitantly with the
      spontaneous duodenal phase III in sheep. 5-HT4 receptors also have a prokinetic
      action in the antral area.

PMID- 9004196
TI  - In-vitro bronchorelaxing effects of novel nitric oxide donors GEA 3268 and GEA
      5145 in guinea-pigs and rats.
AB  - Endogenously released nitric oxide (NO) in airways might contribute to
      physiological bronchodilation; induced production of NO might play a role in the
      pathogenesis of asthma, although it could also be a compensatory mechanism to
      other factors that cause bronchoconstriction or inflammation. To investigate the
      efficacy of NO donors on bronchial tone, the bronchorelaxing efficacies of NO
      donors, new experimental GEA compounds 3268 and 5145 (oxatriazole
      sulphonylamides) were compared with those of sodium nitroprusside and SIN-1 (3
      morpholinosydnonimine) and to the standard beta 2-adrenergic agonist, salbutamol,
      in bronchi of guinea-pigs and rats in-vitro. Their relaxing effects were also
      studied in rat mesentery arteries to compare the selectivity for airways. The
      capacity of the NO donors to produce nitrites and nitrates was assayed by the
      Griess reaction. The novel NO donors GEA 3268 and GEA 5145 were more potent
      bronchorelaxing agents than the old NO donors sodium nitroprusside and SIN-1. In
      guinea-pig bronchi, however, salbutamol was most potent. In rat bronchi the GEA
      compounds induced the strongest relaxation effect when compared with the old NO
      donors or with salbutamol. The airway selectivity of the drugs studied decreased
      in the order of salbutamol, SIN-1, GEA 5145, GEA 3268, sodium nitroprusside. The
      nitrites and nitrates produced spontaneously did not correlate with the efficacy
      of the relaxants. The results obtained suggest that NO is only partly responsible
      for the relaxation and the potency is dependent on the animal species and
      constricting agents used.

PMID- 9004199
TI  - Age-dependent alteration of the serum-unbound fraction of nicardipine, a calcium
      channel blocker, in man.
AB  - To determine whether the age-dependent increase in the pharmacological effect of
      calcium-channel blockers is a result of age-dependent alteration of the unbound
      fraction the drug in serum, the unbound fraction of the nicardipine was
      investigated in the serum of 38 adults. The unbound concentration of nicardipine
      in serum to which nicardipine (205.4 ng mL-1) had been added was determined by
      ultracentrifugation to range from 0.49 to 4.01% (mean +/- s.d., 1.55 +/- 0.78%).
      Non-glycosylated albumin was most strongly correlated with age (r = 0.901). Total
      bilirubin was weakly correlated with age whereas levels of alpha-1-acid
      glycoprotein, triglycerides and glycosylated albumin were not correlated with
      age. A significant (P < 0.01) linear correlation was obtained between the unbound
      fraction of nicardipine and parameters such as age, albumin, albumin/globulin
      ratio, albumin/glycosylated albumin ratio, non-glycosylated albumin and total
      bilirubin. To assess the relative effect of each variable on the unbound fraction
      of nicardipine, stepwise multiple linear regression was performed using age and
      biochemical parameters. The three variables (non-glycosylated albumin, total
      bilirubin and age) were entered into the regression equation. The results of this
      study showed that the major ligand of nicardipine in serum was non-glycosylated
      albumin, which decreased with age. It was, moreover, shown that the serum-unbound
      concentration of nicardipine increased with age. This finding would be one factor
      accounting for the increase in the pharmacological effect of nicardipine with
      age. In addition, our predicted model for the unbound fraction of nicardipine
      might be useful in determining the appropriate nicardipine dose for the elderly.

PMID- 9004197
TI  - Frequency distribution of Candida albicans blastospores adhered to mucosal
      epithelial cells in-vitro.
AB  - Although several methods are available for examination of microbial adherence to
      epithelial cells, these do not distinguish between adherence of viable and non
      viable micro-organisms. This study reports the use of acridine orange-stained
      blastospores of Candida albicans in conjunction with direct epifluorescence
      microscopy to determine viable (orange-fluorescing) and non-viable (green
      fluorescing) blastospore adherence to buccal epithelial cells. The method was
      also employed to examine the effects of chlorhexidine treatment at subminimum
      inhibitory concentrations on the adherence of viable and non-viable blastospores.
      There was good correlation in the assessment of blastospore viability between the
      direct epifluorescence microscopy technique and the standard serial dilution and
      plating method for viable counting, confirming the reliability of direct
      epifluorescence microscopy. Chlorhexidine treatment before acridine orange
      staining did not alter this assessment of viability. Blastospore adherence to
      buccal epithelial cells resulted in a similarly skewed distribution whether
      examined using a crystal violet stain in conjunction with light microscopy or
      using direct epifluorescence microscopy, therefore validating the direct
      epifluorescence microscopy technique for the enumeration of blastospore
      adherence. Chlorhexidine treatment (0.0005% v/v, 30 min) of either blastospores
      or buccal epithelial cells altered the distribution of adherent blastospores per
      epithelial cell by increasing the number of epithelial cells having no adherent
      blastospores. No differences in adherence were, however, observed between
      blastospore or epithelial cells after treatment with this agent. Examination of
      the adherence of viable and non-viable blastospores to buccal epithelial cells
      using direct epifluorescence microscopy revealed a greater adherence capacity of
      non-viable than viable blastospores for buccal epithelial cells. Treatment of
      blastospores with chlorhexidine altered the frequency distributions of viable and
      non-viable blastospores with lower numbers of blastospores adherent per
      epithelial cell. The larger reduction in adherent viable blastospores in
      comparison with their non-viable counterparts is, however, an important
      observation which might have clinical relevance. Microbial cells adhere to
      epithelial cells resulting in a skewed distribution; study of this distribution
      gives useful information about the adherence process. Viable and non-viable
      components of a microbial population have different adherence capabilities and
      treatment of such populations with an antimicrobial agent exerting anti-adherent
      activity at sub-minimum inhibitory concentrations reduces the amount of adherence
      of these viable/non-viable components to different extents.

PMID- 9004198
TI  - The failure of substrate pKa to influence the microsomal formation of amides from
      N-benzylamines: the microsomal metabolism of N-benzyl pyrrolidine, N-benzyl
      carbazole and N-acetyl-N-benzyl-4-methylaniline.
AB  - The in-vitro hepatic microsomal metabolism of N-benzylpyrrolidine (NBP), N
      benzylcarbazole (NBC) and N-acetyl-N-benzyl-4-methylaniline (NANBMA) has been
      studied, using hamster microsomal preparations, to establish whether the
      corresponding amide is formed. Amide formation was not observed with any of the
      substrates utilized, although several metabolic products were detected by HPLC
      with UV detection. These included the oxidative debenzylation products (for all
      substrates), ring hydroxylated products (for NBC) and a lactam metabolite (for
      NBP). The results support the concept that the metabolic conversion of benzylic
      amines to the corresponding amide involves an N-oxidative step.

PMID- 9004215
TI  - Plasmid replication and partition in Escherichia coli: is the cell membrane the
      key?
AB  - The DNA-membrane complex has been the subject of intensive investigation for over
      35 years as the possible site for DNA replication in the prokaryotic cell and the
      site through which newly synthesized chromosomes are segregated into daughter
      cells. However, the molecular mechanisms which control these phenomena are, for
      the most part, poorly understood despite genetic, biochemical, and morphologic
      evidence in favour of their existence. This is probably due to the transient
      nature and non-covalent interactions that occur between DNA and the membrane. In
      addition, there is a paucity of knowledge concerning the nature of the membrane
      receptors for DNA and whether the membrane plays simply a structural or metabolic
      role in the two processes. Plasmids can provide important insights into the role
      of the membrane in replication and partitioning because the plasmid life cycle is
      relatively simple, with replication occurring during the cell cycle and
      partitioning during cell division. The replicon model of Jacob et al. (1963, Cold
      Spring Harbor Symp Quant Biol 28: 329-348) still represents a good conceptual
      framework (with modifications) to explain how plasmid replication and
      partitioning are linked by the membrane. In its simplest form, the model focuses
      on specific membrane binding sites (possibly along the equator of the cell) for
      plasmid (or bacterial) replication, with the membrane acting as a motive force to
      separate the newly synthesized replicons and their attached sites into daughter
      cells. Indeed, proteins involved in both plasmid replication and partitioning
      have been found in membrane fractions and some plasmids require membrane binding
      for initiation and an active partitioning. We propose that several factors are
      critical for both plasmid DNA replication and partitioning. One factor is the
      extent of negative supercoiling (brought about by an interplay of various
      topoisomerases, but most importantly by DNA gyrase). Supercoiling is known to be
      critical for initiation of DNA replication but may also be important for the
      formation of a partition complex in contact with the cell membrane. Another
      factor is the presence of specific subdomains of the membrane which can interact
      specifically with origin DNA and possibly other regions involved in partitioning.
      Such domains may be induced transiently or be present at all times during the
      cell cycle.

PMID- 9004217
TI  - The Aspergillus niger GCN4 homologue, cpcA, is transcriptionally regulated and
      encodes an unusual leucine zipper.
AB  - The general control transcriptional regulator gene cpcA of Aspergillus niger was
      cloned by complementation of a Saccharomyces cerevisiae delta gcn4 mutant strain.
      The encoded protein conferred resistance to amino acid analogues when expressed
      in yeast. Disruption of cpcA in A. niger resulted in a strain which is sensitive
      towards 3-aminotriazole and fails to respond to amino acid starvation, cpcA
      encodes a transcript of approximately 2400 nucleotides in length that includes a
      5' leader region of 900 nucleotides. The 5' leader region contains two small open
      reading frames, suggesting translational control of gene expression. Steady-state
      mRNA levels of cpcA increase by a factor of three upon amino acid starvation. The
      coding region of cpcA is interrupted by a 57 bp intron and the deduced amino acid
      sequence displays an approximately 30% overall identity to yeast GCN4p and
      Neurospora crassa cpc1p. Critical amino acid residues of the transcriptional
      activation domains of GCN4p are conserved in cpcAp. The basic DNA-binding domain
      shows up to 70% amino acid sequence identity to other basic zipper (bZIP)-type
      transcriptional activators. cpcAp binds specifically to a GCN4p recognition
      element in gel retardation experiments. The C-terminal dimerization domain
      encodes a leucine zipper with only a single leucine residue.

PMID- 9004218
TI  - Vitamin B12 repression of the btuB gene in Salmonella typhimurium is mediated via
      a translational control which requires leader and coding sequences.
AB  - Expression of the Salmonella typhimurium btuB gene, which encodes an outer
      membrane protein required for vitamin B12 uptake, is repressed by the presence of
      external vitamin B12. We have, by means of a mutational analysis, investigated
      which btuB sequences are required for repression. Analysis of btuB::lacZ
      transcriptional and translational fusions of various lengths showed that the
      control was exerted mainly at the translational level and required both coding
      and leader sequences in the btuB transcript. Regulatory mutants with a B12 non
      repressible phenotype were isolated and the mutations were shown to be located at
      several sites within the btuB leader. Analysis of constructs carrying site
      directed point mutations, which either destabilized or restabilized a putative
      RNA hairpin that sequesters the btuB ribosomal binding site, demonstrated that
      this hairpin was essential for normal repression. Comparison of the S.
      typhimurium btuB gene with the previously characterized S. typhimurium cbiA and
      Escherichia coli btuB genes reveals significant similarities as well as
      differences in the cis-acting sequences required for repression.

PMID- 9004216
TI  - A mitochondrial-like targeting signal on the hydrogenosomal malic enzyme from the
      anaerobic fungus Neocallimastix frontalis: support for the hypothesis that
      hydrogenosomes are modified mitochondria.
AB  - The hydrogenosomal malic enzyme (ME) was purified from the anaerobic fungus
      Neocallimastix frontalis. Using reverse genetics, the corresponding cDNA was
      isolated and characterized. The deduced amino acid sequence of the ME showed high
      similarity to ME from metazoa, plants and protists. Putative functional domains
      for malate and NAD+/NADP+ binding were identified. Phylogenetic analysis of the
      deduced amino acid sequence of the new ME suggests that it is homologous to
      reference bacterial and eukaryotic ME. Most interestingly, the cDNA codes for a
      protein which contains a 27-amino-acid N-terminus which is not present on the
      purified mature protein. This presequence shares features with known
      mitochondrial targeting signals, including an enrichment in Ala, Leu, Ser, and
      Arg, and the presence of an Arg at position-2 relative to amino acid 1 of the
      mature protein. This is the first report of a mitochondrial-like targeting signal
      on a hydrogenosomal enzyme from an anaerobic fungus and provides support for the
      hypothesis that hydrogenosomes in Neocallimastix frontalis might be modified
      mitochondria.

PMID- 9004220
TI  - Structural relationship between a bacterial developmental protein and eukaryotic
      PP2C protein phosphatases.
AB  - Bacillus subtilis SpoIIE is a Ser protein phosphatase whose action on the
      phosphoprotein SpoIIAA triggers the cell type-specific activation of a
      sporulation transcription factor. Here we report that SpoIIE displays sequence
      similarity to the PP2C family of eukaryotic Ser/Thr protein phosphatases, and
      that residues common to these proteins are required for the function of both
      SpoIIE and TPD1, a yeast PP2C. These findings suggest that SpoIIE and the PP2C
      protein phosphatases are structurally related, and reveal a striking formal
      similarity between the SpoIIAA regulatory circuit and that of mammalian
      mitochondrial pyruvate dehydrogenase. This similarity may reflect an
      evolutionarily conserved mechanism of biological regulation based on the
      interplay of His protein kinase-like Ser kinases and PP2C-like protein
      phosphatases.

PMID- 9004219
TI  - Molecular characterization of mutants affected in the osmoprotectant-dependent
      induction of phospholipase C in Pseudomonas aeruginosa PAO1.
AB  - Production of the two phospholipases C (PLCs) in Pseudomonas aeruginosa PAO1 is
      induced under conditions of phosphate limitation, or by the osmoprotectants
      choline or glycine betaine. Tn5 mutagenesis was performed on strain PAO1 to
      isolate mutants deficient in choline-dependent induction of PLC. Two mutants,
      Tn5T1 and Tn5G19, were identified which produce decreased levels of PLC in
      phosphate-replete media supplemented with choline. A total of 136 and 496 bp of
      flanking DNA from Tn5G19 and Tn5T1 was cloned by an inverse polymerase chain
      reaction (PCR) and sequenced. The DNA flanking the Tn5T1 insertion contains an
      open reading frame predicted to encode a peptide that is approx. 60% identical to
      the N-terminus of a previously identified protein (P35) of unknown function from
      Escherichia coli. The P35 gene, which is located in the nusA-infB operon in E.
      coll, was designated orp (osmoprotectant regulator of PLC). Haemolytic titres,
      total PlcH protein and beta-galactosidase activity expressed from a chromosomally
      inserted plcH-lacZ operon fusion were reduced in strain Tn5T1 in comparison with
      the parental strain (PAO1) carrying the same fusion. However, this mutant
      expressed several-fold higher levels of plcH message than strain PAO1 in the
      presence of choline, while the phosphate-starvation-dependent transcript of plcH
      could not be detected in this mutant. The defects in Tn5T1 are complemented by a
      DNA fragment, isolated from a genomic library of PAO1, that carries the orp gene.
      The deduced amino acid sequence of the DNA fragment cloned from Tn5G19 exhibits
      84% identity with the betB gene product of E. coli that has betaine aldehyde
      dehydrogenase activity. This enzyme catalyses the conversion of betaine aldehyde
      to glycine-betaine. Unlike the parental strain, the Tn5G19 mutant could not
      utilize choline as a sole carbon, nitrogen and energy source, and it was
      deficient in betaine aldehyde dehydrogenase activity. Also, consistent with a
      disruption of betB in Tn5G19, choline inhibited growth of this strain in media
      containing 0.7 M NaCl, while glycine-betaine restores growth to wild-type levels.
      The defects in Tn5G19 are complemented by a DNA fragment from PAO1 that carries
      the betB gene. The orp gene is located between 0.6 to 6.6 min while betB is
      located between 10.5 to 12.5 min on the chromosome of PAO1.

PMID- 9004221
TI  - Molecular and chemical characterization of the lipopolysaccharide O-antigen and
      its role in the virulence of Yersinia enterocolitica serotype O:8.
AB  - The Y. enterocolitica O:8(YeO8) O-antigen repeat units consist of five sugar
      residues: N-acetyl-D-galactosamine (GalNAc), D-galactose (Gal), D-mannose (Man),
      L-fucose (Fuc), and 6-deoxy-D-gulose (6d-Gul). The nucleotide sequence of the O
      antigen gene cluster of the YeO8 strain 8081-c was determined. Altogether, 18
      open reading frames (ORFs) were identified and shown to be essential for O
      antigen biosynthesis. We previously characterized the 3'-end of the O-antigen
      gene cluster and identified four genes: two for GDP-Man biosynthesis, one for UDP
      Gal biosynthesis, and one for O-antigen polymerase. Based on sequence similarity,
      Tn5-insertion phenotypes and chemical analysis, the 14 new genes were assigned
      the following functions: four genes are involved in the biosynthesis of CDP-6d
      Gul and two in GDP-Fuc biosynthesis. Five gene products were assigned sugar
      transferase functions and one gene product was similar to Wzx, the O-antigen
      flippase. Two genes remained unassigned. By genetic complementation we also
      showed that YeO8 O-antigen biosynthesis was dependent on N-acetyl
      glucosaminyl:undecaprenylphosphate transferase (GlcNAc transferase), the WecA
      (formerly known as Rfe) protein. Data obtained from chemical-composition analysis
      suggest that in addition to being GlcNAc transferase, WecA may also function as a
      GalNAc transferase. Using a restriction-deficient derivative of Y. enterocolitica
      O:8 strain 8081, a rough mutant, designated 8081-R2, was isolated. 8081-R2 was
      complemented in trans with a cloned O-antigen gene cluster restoring surface O
      antigen expression. The virulence of the wild-type strain and that of the
      complemented strain were significantly higher (approx. 100-fold) than that of the
      rough mutant in an orally infected mouse model, showing that YeO8 O-antigen is a
      virulence factor.

PMID- 9004222
TI  - Disruption of hspR, the repressor gene of the dnaK operon in Streptomyces albus
      G.
AB  - hspR is the distal gene of the Streptomyces albus dnaK operon. It encodes a
      protein similar to GlnR, the repressor of the Bacillus subtilis glutamine
      synthetase gene. Transcriptional analysis showed that disruption of hspR led to
      constitutive high-level expression of the dnaK operon, SDS-PAGE analysis revealed
      over-production and accumulation of the chaperone DnaK at low temperature HSP94,
      a heat-inducible protein cross-reacting with anti-CipB antibodies, was also shown
      to be constitutively overexpressed at low temperature in the hspR mutant. Those
      features were lost when the mutant was complemented in trans by an intact copy of
      hspR. The hspR mutant was impaired in its growth on solid rich medium: colonies
      grow slowly at 30 degrees C. However, formation of aerial mycelium and
      sporulation was not prevented. In liquid culture growth curves of the mutant and
      the wild type were similar. The kinetics of groEL gene induction were not
      modified by the hspR null mutation, indicating that HspR was not directly
      involved in the control of groEL transcription. Thus, in contrast with B.
      subtilis and other Gram-positive bacteria, transcription of Streptomyces dnaK and
      groEL operons is not controlled by the same regulator.

PMID- 9004223
TI  - The Rhizobium meliloti putA gene: its role in the establishment of the symbiotic
      interaction with alfalfa.
AB  - Little is known about the energy sources used by rhizobia during colonization,
      invasion and root nodule formation on leguminous plants. We have recently
      reported that an impaired proline metabolism in rhizobium meliloti leads to a
      reduced nodulation efficiency and competitiveness on alfalfa roots. In the
      present study we have characterized the R. meliloti proline dehydrogenase gene
      (putA) and addressed the question of its role in symbiosis. This rhizobial gene
      encodes a 1224-amino-acid-long polypeptide which is homologous to enteric
      bacteria, Rhodobacter capsulatus and Bradyrhizobium japonicum PutA proteins. Like
      the situation in these bacteria, sequence analysis identified the proline
      dehydrogenase (PDH) and pyrroline-5-carboxylate dehydrogenase (P5CDH) domains in
      the R. meliloti putA-encoded protein. Beta-galactosidase assays performed with
      free-living cells carrying a putA-lacZ transcriptional fusion revealed that R.
      meliloti putA gene expression is induced by proline, autoregulated by its encoded
      product, and independent of the general nitrogen regulatory system (Ntr). In
      addition, analysis of putA expression during the different steps of the symbiotic
      interaction with alfalfa showed that expression of this gene is turned on by the
      root exudates (RE), during root invasion and nodule formation, but not in
      differentiated nitrogen-fixing bacteroids. Furthermore, we show that the PutA-
      phenotype leads to a significant reduction of alfalfa root colonization by R.
      meliloti.

PMID- 9004224
TI  - Replication control of plasmid pLS1: the antisense RNA II and the compact rnaII
      region are involved in translational regulation of the initiator RepB synthesis.
AB  - Replication of the streptococcal plasmid pLS1 is controlled by two plasmid
      encoded gene products: the repressor protein CopG and the antisense RNA, RNA II.
      Two different mutants in rnaII have been isolated. The 5'-end and the levels of
      RNA II synthesized by pneumococcal cells harbouring the wild-type pLS1 or mutant
      plasmids (affected in either genes copG or rnaII) were analysed. One of the rnaII
      mutants exhibited a high-copy-number phenotype, whereas an in vitro-constructed
      mutation, which affects the -10 region of the rnaII promoter, resulted in
      plasmids lacking copy-number phenotype. The latter mutation had a pleiotropic
      effect: It abolished RNA II synthesis, but it also affected the initiation of
      translation signals of the gene encoding the RepB initiator protein.
      Transcriptional and translational fusions, together with in vitro inhibition of
      RepB synthesis by specific oligonucleotides, showed translational inhibition of
      RepB synthesis by RNA II, perhaps by directly blocking the accessibility of the
      ribosomes to the repB initiation of translation signals.

PMID- 9004225
TI  - The Myxococcus xanthus pilT locus is required for social gliding motility
      although pili are still produced.
AB  - Social gliding motility in Myxococcus xanthus depends on the presence of Type IV
      pili. To begin to examine the role of pili in social motility, 17 mutants were
      identified which had lost social motility, but still expressed pili. Four of
      these mutants carry point mutations which mapped to a locus upstream of the
      recently identified pilS, pilR, and pilA genes. Sequencing of this locus revealed
      a gene with homology to pilT from Pseudomonas Aeruginosa. Sequencing of the four
      point mutations revealed that they occurred within the M. xanthus pilT locus. A
      markerless deletion within M. xanthus pilT, similar to the four point mutations,
      disrupted social gliding behaviour but did not interfere with pilus formation or
      pilus-dependent cell-cell agglutination. Using time-lapse videomicroscopy,
      residual social motility was observed in dsp- strains (known to be deficient in
      fibril but not pilus production); this was not observed in a delta pilT dep-
      double mutant. Two genes flanking pilT were also sequenced, and found to have
      homology to pilB and pilC from P. aeruginosa. Markerless deletions within these
      genes caused both pilus and social-motility defects. These results indicate that
      M. xanthus pilB and pilC are required for pilus biogenesis, while pilT is
      required for assembled pili to play their role in social motility. Thus, pilB,
      pilT, pilC, pilS, pilR and pilA form a contiguous cluster of pil genes required
      for social motility.

PMID- 9004226
TI  - Promoter strength influences phase variation of neisserial opa genes.
AB  - The opa multigene family of Neisseria gonorrhoeae encodes 11 related outer
      membrane proteins which phase vary in vitro and in vivo. Illegitimate
      recombination within direct pentameric DNA repeats, encoding the signal-peptide
      region of pre-Opas, leads to switches in expression states. Despite the conserved
      nature of the variation mechanism, specific genes are expressed at high
      frequencies in the transition from Opa- to Opa+. The genes which are expressed at
      elevated frequencies differ from the rest of the family with respect to promoter
      structure, based on sequence comparisons between the opa genes of strain MS11mk.
      We have analysed transcription of the opa gene family of N. gonorrhoeae MS11mk,
      focussing on the different promoters found among the 11 genes to determine
      whether increased levels of expression are associated with increased phase
      variation rates. Primer extension and Northern blotting was used to assess the
      levels of transcription of three representative opa genes (opaA, B and C) in 'on'
      and 'off' states. Full-length opa mRNA was detected primarily in strains
      expressing the homologous gene. Truncated opa mRNA was constitutively expressed
      from all opa genes regardless of their expression state. Quantitative comparisons
      in N. gonorrhoeae were complicated by the simultaneous expression of all 11 genes
      and the cross-reactivity of mRNA probes. Expression levels from the individual
      promoters were therefore assessed by creating transcriptional and translational
      lacZ fusions to each of the representative opa promoters which lacked the DNA
      repeats responsible for variation. The expression levels were compared to the
      phase-variation rates of translational opa::phoA fusions containing the same
      promoters in addition to the corresponding coding repeat regions. A strong
      correlation was found between expression levels from the different promoters and
      the variation rates at which 'on' variants appeared from an 'off' population
      (i.e. opaA > opaB > opaC). These results provide an explanation for the favoured
      expression of specific Opa proteins and indicate that expression of opa genes may
      be regulated at the level of transcription.

PMID- 9004227
TI  - A conserved helicase motif of the AddA subunit of the Bacillus subtilis ATP
      dependent nuclease (AddAB) is essential for DNA repair and recombination.
AB  - Various mutations were introduced in a conserved helicase domain (motif VI) of
      the AddA subunit of the Bacillus subtilis ATP-dependent nuclease (AddAB) by site
      directed mutagenesis. These mutations affected the helicase activity and the ATP
      dependent exonuclease activity on double-stranded DNA (dsDNA) as the substrate to
      various degrees, but had hardly any effect on the exonuclease activity on single
      stranded DNA (ssDNA), suggesting that exonuclease activity on dsDNA of the enzyme
      requires unwinding of the DNA. This idea was supported by the finding that,
      initially, the rate and extent of unwinding of the DNA were higher than those of
      its degradation to acid-soluble products by the exonucleolytic activity. The
      effects of the mutations on DNA repair and recombination correlated strongly with
      their effects on helicase activity. Taken together, these results suggest that
      motif VI is essential for the helicase activity, and that this activity is
      required for DNA repair and recombination.

PMID- 9004228
TI  - Characterization of a mitogen-activated protein (MAP) kinase from Plasmodium
      falciparum.
AB  - A mitogen-activated protein (MAP) kinase gene, PfMAP, from Plasmodium falciparum
      was recently identified. We expressed this gene in Escherichia coli to test
      whether it encodes a functional MAP kinase. Recombinant PfMAP kinase
      autophosphorylates on both the tyrosine and threonine residues within the TXY
      motif, and readily phosphorylates myelin basic protein as exogenous substrate.
      This identifies the PfMAP gene product as a true member of the growing family of
      MAP kinases. Wild-type PfMAP kinase expressed in COS-7 (SV40 transformed African
      green monkey kidney) cells seemed to induce apoptosis in these cells. Western
      blots and immunoprecipitations indicated that the kinase is expressed during the
      growth of the parasite in the red blood cell as three major forms: truncated
      forms with apparent molecular masses of 40 kDa and 80 kDa, and as a protein of
      approximately 150 kDa. The 40 kDa form is present throughout the
      intraerythrocytic development, whereas the two larger forms are only detected in
      mature parasites. The 40 kDa and 80 kDa forms are tyrosine phosphorylated,
      indicating that they represent the active forms of the PfMAP kinase. The total
      PfMAP kinase activity constantly increases with the maturation of the parasite.

PMID- 9004229
TI  - The leader peptide is essential for the post-translational modification of the
      DNA-gyrase inhibitor microcin B17.
AB  - Microcin B17 (MccB17) is a ribosomally encoded DNA-gyrase inhibitor. Ribosomally
      encoded antibiotics are derived from precursors containing an N-terminal leader,
      which is removed during maturation, and a C-terminal structural peptide.
      PreMccB17, the translational product of mcbA, is modified into proMccB17 by the
      action of three enzymes, McbB, McbC, and McbD. A chromosomally encoded peptidase
      then converts proMccB17 into MccB17. The role of McbB, McbC, and McbD is to
      convert glycine, cysteine, and serine residues present in preMccB17 into four
      thiazole and four oxazole rings. Using a modification-specific antibody rather
      than antimicrobial activity, we show that the 26-amino-acid N-terminal leader of
      preMccB17 is essential for the conversion of preMccB17 into proMccB17. Neither a
      preMccB17 peptide lacking the leader nor a preMccB17-beta-galactosidase fusion
      lacking the leader are post-translationally modified.

PMID- 9004230
TI  - Sigma-E is required for the production of the antibiotic actinomycin in
      Streptomyces antibioticus.
AB  - The phsA gene encodes phenoxazinone synthase (PHS), which catalyses the
      penultimate step in the pathway for actinomycin biosynthesis in Streptomyces
      antibioticus. The phsA promoter strikingly resembles a putative Streptomyces
      sigma E cognate promoter, and purified E sigma E holoenzyme transcribed the phsA
      promoter in vitro. However, the phsA promoter was still active in an S.
      antibioticus sigE null mutant and the level of PHS activity was unaffected.
      Despite this, disruption of sigE blocked actinomycin production completely. The
      loss of actinomycin production correlated with a 10-fold decrease in the activity
      of actinomycin synthetase I, the enzyme which catalyses the activation of the
      precursor of the actinomycin chromophore.

PMID- 9004231
TI  - The per regulator of enteropathogenic Escherichia coli.

PMID- 9004232
TI  - Transcription factors in early development of the central nervous system.
AB  - In studies of the central nervous system (CNS) few areas have progressed faster
      than the study of transcription factors and their role in controlling gene
      expression during development. Evidence for the pivotal roles of these factors in
      the formation of the CNS is reviewed; from neural induction to the maturation of
      neurons and the specification of cells according to their position within the
      CNS. In all of these processes, epigenetic factors affect the cells'
      developmental fate but it is transcription factors within the cells which
      function both to decode these incoming messages and then to effect changes in the
      expression of other genes. Soluble factors such as retinoic acid and the products
      of the Noggin and Sonic hedgehog genes induce changes in families of
      transcription factors such as the Hox, Sox, Pax and Pou gene products and these
      alter the expression of banks of downstream genes thereby controlling the
      developmental fate of those cells. Recent advances in understanding of the
      molecular events underlying normal neurogenesis might now lead to a clearer
      understanding of the molecular abnormalities underlying several developmental
      disorders of the CNS.

PMID- 9004233
TI  - Cellular immediate-early genes and cell death in the nervous system.

PMID- 9004234
TI  - Cell death in the normal developing brain, and following ionizing radiation,
      methyl-azoxymethanol acetate, and hypoxia-ischaemia in the rat.
AB  - Naturally occurring (programmed) cell death in the developing brain has
      morphological characteristics of apoptosis and is associated with
      internucleosomal DNA fragmentation. Apoptosis also plays a role in cell death
      following hypoxia-ischaemia in the developing rat brain. Ionizing radiation
      induced cell death in the brain of the young rat has morphological
      characteristics of apoptosis, is mediated by protein synthesis and is associated
      with internucleosomal DNA fragmentation. Methyl-azoxymethanol (MAM) acetate
      injection in the young rat produces apoptotic cell death in the external granule
      cell layer of the cerebellum. In addition, strong c-Jun immunore-activity is
      observed in apoptotic cells during normal development and following
      experimentally induced cell death. Moreover, c-Jun mRNA induction and de novo c
      Jun protein synthesis, together with activation of c-Jun/AP-1, as revealed with
      gel mobility shift assay, occurs in irradiated animals. Western blotting of total
      brain homogenates shows a c-Jun-immunoreactive band at p39, which corresponds to
      the molecular weight of c-Jun, in control rats. However, a thick c-Jun
      immunoreactive band at about p62, accompanied by a decrease of the p39 band,
      occurs in irradiated and MAM-treated rats. A thin band immediately above the
      thick p62 band, suggestive of c-Jun phosphorylation, is also observed in treated
      rats. Taken together, these observations indicate that c-Jun expression is
      associated with apoptotic cell death in the developing central nervous system.

PMID- 9004235
TI  - Apoptosis in perinatal hypoxic-ischaemic cerebral damage.
AB  - Perinatal hypoxia-ischaemia induces a biphasic cerebral injury: the depletion in
      high energy phosphates during the insult returns to normal soon after
      resuscitation. However, some 8-15 h later a second phase of impaired energy
      metabolism begins, which is related to the severity of later neurodevelopmental
      impairment. Delayed injury differs from acute hypoxia-ischaemia because
      intracellular acidosis does not occur. Apoptosis may be a mechanism of delayed
      cellular injury. Apoptotic cells and typical DNA fragmentation have been found
      after perinatal hypoxia-ischaemia. In newborn piglets, fraction of apoptotic
      cells was directly related to the degree of high energy phosphate depletion
      during hypoxia-ischaemia. Apoptosis may be interrupted: in piglets, brain cooling
      for 12 h following resuscitation reduced the fraction of apoptotic but not
      necrotic cells. These results have implications for both the understanding of
      cerebral injury and the use of hypothermia as a neural rescue strategy in the
      developing brain.

PMID- 9004236
TI  - Developmental spectrum of the excitotoxic cascade induced by ibotenate: a model
      of hypoxic insults in fetuses and neonates.
AB  - Ibotenate, a glutamatergic agonist, was used to study the spectrum of excitoxic
      disturbances at different ages of cerebral development. Cultures of whole mouse
      embryo were submitted to ibotenate at E8 for 20 h: during the phase of early
      premigratory differentiation: ibotenate did not induce any detectable
      histological lesion. During migration of supragranular neurons, newborn hamsters
      intracerebrally injected at PO with ibotenate display neuronal migration
      disorders graded from nodular heterotopias to extensive laminar heterotopias
      mimicking some aspects of lissencephalic and double-cortex syndromes. After
      completion of neuronal layer V, PO mice injected with ibotenate exhibit laminar
      neuronal depopulation of layer V-VIa mimicking human microgyria. At P5 in mouse,
      after completion of neuronal migration of the cortical plate, ibotenate induces
      neuronal loss in all cortical layers and the formation of porencephalic cysts.
      This study emphasizes the dramatic role played by glutamate in brain development,
      in the occurrence of neuronal migration disorders in the cortex, and in grey and
      white matter damage.

PMID- 9004237
TI  - Blunt head injury: prospects for improved outcome.

PMID- 9004238
TI  - The spectrum of traumatic axonal injury.

PMID- 9004239
TI  - Forensic-neuropathological aspects of brain injuries in child abuse.

PMID- 9004240
TI  - Genetics and head injury.

PMID- 9004241
TI  - Pathophysiology of spinal cord trauma: observations on vasogenic oedema and
      axonal injuries in human and experimental material.

PMID- 9004242
TI  - Amyloid deposition is associated with c-Jun expression in Alzheimer's disease and
      amyloid angiopathy.
AB  - Since the PAD gene (also called promoter of Alzheimer's disease amyloid A4
      precursor gene or amyloid beta-protein precursor promoter) has two AP-1 consensus
      sequences, and members of the Fos and Jun families are the major components of
      the transcription factor activator protein-1 (AP-1), we have investigated the
      localization of c-Fos and c-Jun immunoreactivity and its relationship to beta
      amyloid deposition in the brains of patients with Alzheimer's disease and amyloid
      angiopathy. c-Jun, but not c-Fos, immunoreactivity is observed in the muscular
      layer of meningeal and cerebral blood vessels with amyloid angiopathy, and in the
      soma of glial cells and cellular processes of unknown origin surrounding beta
      amyloid deposits in the brain. These results show that c-Jun may participate in
      the cascade of events leading to increased beta-APP (beta-amyloid precursor
      protein) production and beta-amyloid deposition in the brains of patients with
      Alzheimer's disease and amyloid angiopathy.

PMID- 9004243
TI  - Correlations between the morphology of diffuse and primitive beta-amyloid (A
      beta) deposits and the frequency of associated cells in Down's syndrome.
AB  - Correlations between the morphology of beta-amyloid (A beta) deposits and the
      frequency with which they are associated with neurons and glial cells were
      studied in Down's syndrome. The diameter of diffuse deposits was positively
      correlated with the frequency of large (> 25 microns) neuronal cell bodies in the
      isocortex and with glial cells in the hippocampus. Diameters of primitive
      deposits were positively correlated with glial cells in the hippocampus and with
      glial cells and neurons in the isocortex. Staining intensity was positively
      correlated with glial cells especially in the hippocampus. The data suggest that:
      (i) diffuse deposits develop from neurons and primitive deposits from glia; (ii)
      the size of A beta deposits depends on the numbers of neurons and glia; (iii)
      glial cells are also involved in the conversion of A beta to amyloid; and (iv)
      the increased density of primitive deposits in the hippocampus is determined by
      the high density of glial cells.

PMID- 9004244
TI  - Age-related changes in the olfactory system of dogs.
AB  - Age-related changes in the olfactory system were examined in 22 dogs ranging in
      age from 10 to 19 years old. Atrophic changes with degeneration were observed in
      the olfactory epithelium of dogs older than 14 years; the changes were prominent
      in the dogs over the age of 17 years. Immunohistochemistry using an anti
      carnosine antibody, which is a marker for the olfactory cells, demonstrated a
      decrease in the number of olfactory cells. Electron microscopy also showed a
      decrease in the number of cilia of olfactory cells and microvilli of supporting
      cells. Atrophic changes with the features of regeneration were rarely observed in
      the aged animals. Lipofuscin-like granules in the olfactory epithelium became
      prominent with age. These age-related changes were similar to those reported in
      the olfactory epithelium of man and rats. Dystrophic neurites were not detected
      by a modified Bielschowsky stain or by neurofilament, synaptophysin and tau
      immunohistochemistry in the olfactory mucosa. There was no beta-amyloid- and
      ubiquitin-immunostaining in the olfactory mucosa. Senile brain changes, including
      cerebrovascular amyloidosis, age-related astrocytic gliosis and ubiquitin
      deposits were found in the olfactory bulb, although neurofibrillary tangles and
      senile plaques were not detected either by a modified Bielschowsky stain or by
      beta-amyloid immunohistochemistry. These results indicate that dog may be a
      useful animal model to study the age-related changes in the olfactory system in
      man.

PMID- 9004245
TI  - Morphology of oligodendrocytes during demyelination in optic nerves of mice
      infected with Semliki Forest virus.
AB  - Multiple sclerosis (MS) is a demyelinating disease which affects
      oligodendrocytes, the myelinating cells of the CNS. Demyelination is known to
      occur in the optic nerves of Balb/c mice infected with the avirulent A7(74)
      strain of Semliki Forest virus (SFV), and many of the changes are similar to
      those of patients with MS. The aim of the present study was to determine how
      demyelination proceeds in individual oligodendrocytes in SFV infection, to help
      in understanding the pathology of demyelination and remyelination in MS. The
      whole-cell morphology of individual oligodendrocyte units (defined as the
      oligodendrocyte, its processes and the internodal myelin segments of the axons it
      ensheaths) was characterized using intracellular dye injection in isolated intact
      optic nerves. In untreated control mice, oligodendrocytes had a relatively
      uniform morphology and each cell on average provided 20 or so nearby axons with
      single myelin sheaths with internodal lengths of approximately equal to 150
      microns. In SFV infected mice, during the peak of demyelination at post
      inoculation days 14-21, 55% of oligodendrocytes displayed a range of
      morphological abnormalities, which most likely represented sequential changes in
      oligodendrocytes during demyelination. Thus, at the earliest stage of
      demyelination oligodendrocytes developed swellings or vacuolations along their
      internodal myelin sheaths, which became gradually attenuated and were completely
      lost in extreme cases. The results show that whole oligodendrocyte units were
      affected during SFV-induced demyelination and this is the basis of the focal
      nature of lesions in this viral model of MS. Individual oligodendrocyte units
      which had lost their full complement of myelin sheaths had the appearance of
      immature oligodendrocytes, suggesting they had undergone dedifferentiation. We
      concluded that these cells may not be destroyed during demyelination and it is
      possible they are capable of remyelination which is a feature of SFV infection in
      mice and MS in humans.

PMID- 9004246
TI  - Cryopreservation of organotypic multicellular spheroids from human gliomas.
AB  - Fresh human glioma tissue can be cultured on agarose to form organotypic
      multicellular spheroids (OMS). The major advantage of OMS is the preservation of
      the cellular heterogeneity and the tumour architecture, which is lost in
      conventional monolayer cultures. The present study was undertaken to assess the
      possibilities of storing frozen OMS from seven gliomas which were frozen to
      determine the viability after thawing. OMS were frozen slowly to -196 degrees C
      using a programmable freezing machine in culture medium containing 45% serum and
      10% of the cryopreservative agent dimethyl sulphoxide (DMSO). After 2 weeks
      storage at -196 degrees C, quick thawing, and culturing for another week, it
      appeared that the frozen-thawed OMS were viable and retained their histological
      characteristics. In addition, it is demonstrated that the cellular constituents
      of the OMS resumed metabolic and proliferative activities. It is concluded that
      it is possible to establish frozen stocks of viable glioma OMS. This will enable
      extensive studies on OMS, such as investigation of the biological behaviour of
      gliomas by using OMS obtained from primary and corresponding recurrent gliomas.
      In addition, cryopreservation of OMS makes it possible to correlate the results
      of in vitro tests on OMS with the patients' responses to similar therapeutic
      approaches.

PMID- 9004248
TI  - Role of endogenous bombesin-peptides during vagal stimulation of gastric acid
      secretion in the rat.
AB  - The stimulatory effect of exogenous bombesin and its related mammalian peptides
      on gastric acid secretion and gastrin release has been examined in detail, while
      the regulatory role of endogenously released bombesin-like peptides is largely
      unknown. Accordingly we have determined the effect of a specific bombesin
      receptor antagonist during vagal stimulation of gastric acid secretion and
      gastrin release. In anesthetized rats electrical stimulation of the vagal nerves
      (10 V, 10 Hz, 1 ms) significantly increased plasma gastrin levels by 82 +/- 11
      pg/20 min (P < 0.01) and gastric acid output by 99.4 +/- 9.9 mueq/20 min (P <
      0.01). Intravenous infusion of the specific bombesin receptor antagonist D-Phe6
      BN(6-13)OMe (400 nmol/kg/h) significantly reduced vagally induced increase of
      plasma gastrin levels by 70% to 29 +/- 8 pg/20 min (P < 0.05 vs control) and
      vagally stimulated gastric acid output by 40% to 57.4 +/- 10.6 mueq/20 min (P <
      0.05 vs control). To demonstrate that the residual gastrin and acid response is
      due to non-bombesinergic mechanisms and not to an inadequate dose of the receptor
      antagonist, the latter was tested against gastrin-releasing peptide (GRP) at the
      maximally effective concentration of 300 pmol/kg/h, which resulted in an even 50%
      higher increase of plasma gastrin levels compared to vagal stimulation. The dose
      of the antagonist employed (400 nmol/kg/h) was sufficient to abolish GRP-induced
      stimulation of gastrin and gastric acid secretion. Previously it has been
      postulated that endogenous bombesin-peptides can stimulate acid secretion via
      gastrin-independent mechanisms. To investigate this possibility further the
      effect of the antagonist was examined on vagally induced acid secretion while
      gastrin levels were restored to the range of the respective control experiments.
      In presence of the antagonist the infusion of gastrin-17 (15 pmol/kg/h) in
      addition to vagal stimulation elevated plasma gastrin to levels not different
      from those during vagal stimulation alone. With identical plasma gastrin levels
      the bombesin receptor antagonist had no effect on vagally stimulated acid
      secretion (86.3 +/- 10.7 mueq/20 min vs 99.4 +/- 9.9 mueq/20 min in the controls;
      n.s.). In conclusion, the present data demonstrate for the first time that in
      rats in vivo endogenous bombesin peptides contribute to vagal stimulation of
      gastrin release and gastric acid secretion. Furthermore, endogenous bombesin
      peptides exert their action on parietal cell function via an increase of gastrin
      release, while non-gastrinergic mechanisms are unimportant under the experimental
      conditions employed.

PMID- 9004247
TI  - NADPH-diaphorase activity and vasopressin in the paraventricular nucleus of the
      hypothalamus following adrenalectomy.
AB  - In order to investigate novel neuroendocrine functions of the nitric oxide
      synthesizing enzyme a combined histochemical and immunocytochemical study focused
      on the paraventricular nucleus of the hypothalamus was conducted to check a
      possible influence of bilateral adrenalectomy on three different neuronal
      populations, NADPH diaphorase (ND)-positive, vasopressin (VP)-immunoreactive and
      neurons expressing both markers. In the adrenalectomized animals, a slight
      increase (P > 0.05) of the number of ND magnocellular neurons was detected,
      whereas no changes were observed in the ND-parvicellular population and in the
      neurons showing coexistence (magno- and parvicellular) (P > 0.05). By contrast,
      following bilateral adrenalectomy, a significant increase (P < 0.05) in the VP
      parvicellular population (anterior, medial and periventricular subdivisions) was
      detected, which was reversed when the animals received daily doses of
      corticosterone. These results suggest that nitric oxide is not closely related to
      the hypothalamic regulation of the adenocorticotropin secretion exerted by the
      paraventricular nucleus.

PMID- 9004250
TI  - Cholecystokinin modulation of spontaneous and excitatory amino acid-induced
      activity in the opossum cerebellum.
AB  - Cholecystokinin-B (CCK-8) is an octapeptide that was initially described in the
      gastrointestinal tract. Recent studies have shown that this peptide also has an
      extensive distribution in the central nervous system, including the cerebellum of
      the opossum. In addition to the protein, binding sites for CCK-8 also have been
      described in the granule cell and molecular layer of this species. These
      anatomical data suggest that CCK-8 has a functional role in cerebellar circuitry.
      In the present study we have determined the physiological effects of CCK-8 on
      spontaneous and amino acid-induced activity. The results indicate that this
      peptide has both excitatory and inhibitory effects on spontaneous activity as
      well as the excitatory responses elicited by application of the excitatory amino
      acids aspartate, glutamate and quisqualate. The data suggest that CCK-8 may
      influence more than one population of cerebellar neurons. The findings support a
      neuromodulatory role for this peptide in cerebellar circuitry.

PMID- 9004249
TI  - Influence of nitric oxide on hypoglycemia--or angiotensin II-stimulated ACTH and
      GH secretion in normal men.
AB  - In order to establish whether nitric oxide (NO) is involved in the regulation of
      ACTH and/or GH secretion, normal male subjects were treated i.v. with the NO
      synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (40
      micrograms/kg injected plus 50 micrograms/kg infused over 60 min) in basal
      conditions and/or during stimulation with insulin (0.15 IU/kg body weight in an
      i.v. bolus) to induce hypoglycemia (ITT) or ASP 1 ILE-5 angiotensin II (ANG II)
      (increasing doses of 4, 8 and 16 ng/kg/min, each dose for 20 min). The
      administration of L-NAME neither changed the basal secretion of ACTH and GH nor
      modified the hormonal responses to ANG II stimulation. Also the GH response
      during ITT remained unchanged in the presence of L-NAME. In contrast, the ACTH
      response to hypoglycemia was significantly higher when L-NAME was administered.
      These data suggest that in normal men NO has a negative effect on ACTH secretion,
      but not GH secretion, in response to hypoglycemia. Furthermore, our results argue
      against a role of NO in the control of basal and ANG II-stimulated ACTH and GH
      secretions.

PMID- 9004251
TI  - Chronic administration of ORG 2766 for 6 months produces a subtle impairment in
      strategic learning by rats.
AB  - Rats were administered saline or 10 micrograms of the ACTH4-9 analog ORG 2766 on
      alternate days for 160 days (i.e. 80 injections total). Behavioral assessments
      began 1 week later. Locomotor competence was assessed by examining the number of
      slips and falls made by the animals on a rotating rod. The rats were also trained
      on a position task and 10 subsequent position reversals in a 'T' shaped water
      maze. Exposure to ORG 2766 failed to affect either locomotor competence or the
      overall number of errors committed while learning the original position habit and
      10 reversals. However, the response accuracy of the ORG 2766-treated animals on
      trial 2 of the reversals was equivalent to that expected by chance (58% correct
      choices), whereas saline-treated animals effectively altered their behavior after
      experiencing nonreinforcement on the initial trial of a reversal (77% correct
      choices). This result is consistent with other observations revealing that ORG
      2766 can influence attention and, therefore, some cognitive functions.

PMID- 9004252
TI  - CGRP in the trigeminal nucleus, spinal cord and hypothalamus: effect of gonadal
      steroids.
AB  - Calcitonin gene-related peptide (CGRP) contents were assayed in cervical spinal
      cord, trigeminal nucleus and hypothalamus throughout the estrous cycle and in
      male and ovariectomized rats. In the trigeminal nucleus, neither testosterone nor
      17 beta-estradiol seem to affect CGRP accumulation, but progesterone seems to
      decrease it. In the cervical spinal cord, ovarian steroids seem to decrease CGRP
      while testosterone does not seem to influence it. In the hypothalamus, CGRP was
      only detectable in the male rat suggesting a positive effect of testosterone. It
      had marked circadian rhythm. In conclusion, CGRP content appears to be affected
      by gonadal steroids in the hypothalamus, the cervical spinal cord and the
      trigeminal nucleus in the rat.

PMID- 9004253
TI  - Endothelin-1 induces GM-CSF, IL-6 and IL-8 but not G-CSF release from a human
      bronchial epithelial cell line (BEAS-2B).
AB  - Endothelin (ET) is a powerful vasoconstrictor and bronchoconstrictor peptide that
      may be involved in the pathogenesis of bronchial asthma. We have investigated the
      effect of ET on the secretion of IL-6, IL-8, GM-CSF and G-CSF in a bronchial
      epithelial cell line (BEAS-2B). Incubation of BEAS-2B cells with ET-1 (10(-13) to
      10(-7) M) for 4 h caused dose-related increases in the release of IL-8 (68%
      increase above control, P < 0.001) and IL-6 (43% increase above control, P <
      0.001), compared to untreated control cells. After 48 h incubation, ET-1 also
      increased the release of IL-8 by 35% (P < 0.001) and GM-CSF by 38% (P < 0.01). ET
      1 had no significant effect on G-CSF release. ET-1 did not induce cell
      proliferation at 24 or 48 h. Since ET-immunoreactive materials are expressed in
      epithelial cells in asthma, it is possible that ET-1 of epithelial origin may act
      in a paracrine or autocrine fashion on airway epithelial ET receptors to
      stimulate IL-8, IL-N6 and GM-CSF release. Thus, ET-1 may play a role in the
      regulation of the cytokine responses involved in inflammation of the airway
      mucosa.

PMID- 9004254
TI  - Pattern of distribution of neuropeptides in the camel lacrimal gland.
AB  - The pattern of distribution of neuropeptides, including neuropeptide-Y (NPY),
      vasoactive intestinal polypeptide (VIP), neurotensin (NT), serotonin (5-HT),
      galanin (GAL), leucine-enkephalin (LEU-ENK) and calcitoningene-related-peptide
      (CGRP), in the nerves of the camel lacrimal gland was investigated using
      immunohistochemical techniques. Fresh lacrimal gland segments, obtained from
      adult camels slaughtered in the local abattoir, were used for the
      immunohistochemical techniques. NPY and LEU-ENK immunoreactivity was observed in
      the nerve cell bodies and nerve fibers of the camel lacrimal gland. VIP, GAL and
      CGRP were demonstrated predominantly in fine varicose nerve fibers lying on the
      basolateral surfaces of the lacrimal acinar cells. NT and 5-HT were identified
      mainly in neurons situated in the periacinar regions, close to the basal surfaces
      of the acinar cells. It is concluded that the camel lacrimal nerves contain
      several neuropeptides including NPY, VIP, NT, 5-HT, GAL, LEU-ENK and CGRP which
      may modulate lacrimal fluid and protein secretion.

PMID- 9004255
TI  - Molecular cloning and functional characterization of the oxytocin receptor from a
      rat pancreatic cell line (RINm5F).
AB  - Oxytocin (OT) and vasopressin (AVP) stimulate insulin and glucagon release from
      the pancreas, and evoke insulin secretion from the rat insulinoma cell line,
      RINm5F. To determine which AVP/OT receptor subtype is expressed in RINm5F cells,
      we used PCR with degenerate primers to two transmembrane domains of the AVP (V1a,
      V1b (or V3), V2) and OT receptors (OTRs). The single PCR fragment identified was
      used to obtain a full length cDNA from a RINm5F cDNA library. Comparison of the
      deduced amino acid sequence of this clone with uterine OTR sequences from several
      species (human, sheep, bovine) and to the pig kidney epithelial cell (LLC-PK1)
      OTR reveals a very high degree of homology. After the RIN cell OTR cDNA was
      stably transfected into CHO cells (CHO-OTR), the cell membranes bound iodinated
      oxytocin antagonist with an apparent Kd comparable to that of RIN cell membranes
      and those from other OT target cells. Comparison of the ligand specificities of
      CHO-OTR and RIN cells membranes showed that the relative Ki values of a series of
      OT analogues were approximately equivalent in both preparations. The rank order
      of apparent Ki values also corresponded to published values for the rat
      myometrium, where OT elicits intracellular calcium transients, and increases
      inositol phosphate production. In uterin endometrium and amnion cells, OT
      stimulates prostaglandin release. Stimulation of CHO-OTR cells with OT caused an
      increase in cytosolic calcium concentration originating from both intracellular
      and extracellular sources, and a dose-dependent increase in inositol phosphate
      levels. Arachidonic acid release and PGE2 synthesis were also stimulated by OT.
      These findings (amino acid sequence homology, binding specificity, and signal
      transduction/second messenger production) suggest that OTRs from RINm5F cells are
      indistinguishable from OTRs that have been described in other tissues. The
      expression of OTR in pancreatic cells implies that OT plays a role in pancreatic
      function.

PMID- 9004256
TI  - Pituitary adenylate-cyclase activating polypeptide (PACAP) evokes long-lasting
      secretion and de novo biosynthesis of bovine adrenal medullary neuropeptides.
AB  - Recently, the pituitary adenylate-cyclase activating polypeptide (PACAP) has
      emerged as a potential noncholinergic neuromodulator of adrenal medullary
      function. In support of this hypothesis, we documented PACAP's effects on the
      secretion and biosynthesis of neuropeptides by cultured bovine chromaffin cells.
      Data presented in this study indicate that PACAP is a potent and efficacious
      secretagogue of leucine-enkephalin which was coreleased with catecholamines with
      identical profiles. In comparison to nicotinic activation, however, rates of
      PACAP-induced secretion were substantially slower but persisted for several hours
      causing a prolonged increase in the tonic release of both transmitters and
      peptides. Interestingly, renewal of intracellular pools of neuropeptides was also
      stimulated by PACAP but not the vasoactive intestinal peptide (VIP). Indeed, the
      higher incorporation of [35S]-labeled amino acids into atrial and brain
      natriuretic peptides (ANP, BNP) provided strong evidence that PACAP directly
      activated de novo biosynthesis. Of particular importance was PACAP's net
      preferential stimulation of the biosynthesis of BNP, similar to the differential
      regulation by protein kinase A (PK-A) and protein kinase C (PK-C) activators we
      have previously the differential regulation by protein kinase A (PK-A) and
      protein kinase C (PK-C) activators we have previously reported. PACAP-induced
      secretion and biosynthesis appeared to be mediated by the PACAP-specific type I
      receptors known to activate adenylate cyclase and phospholipase C. We verified
      that PACAP did indeed stimulate the production of cyclic AMP and inositol
      phosphates in our cell system. These findings suggest that the dual signaling
      properties of type I receptors may be important for PACAP's differential effect
      on the biosynthesis of natriuretic peptides. We conclude that PACAP might assume
      important noncholinergic trans-synaptic regulation of the adrenal medulla by
      releasing and modifying intragranular catecholamine and neuropeptide contents.

PMID- 9004258
TI  - Transient upregulation of the AT2 receptor mRNA level after global ischemia in
      the rat brain.
AB  - The present study examined changes in angiotensin receptors (AT1 and AT2) and
      angiotensinogen mRNA level after global ischemia in the rat brain. The AT2 mRNA
      level increased by three-fold in both the cortex and hippocampus, which are known
      to be sensitive to ischemic injury, 3 h after ischemia. The increase thus
      appeared only during the early reperfusion period. In the striatum, amygdala and
      cerebellum, the level increased moderately 3 h and/or 24 h after ischemia; there
      was no change in the hypothalamus. On the other hand, the AT1A and AT1B receptor
      mRNA levels were not altered in the cortex or hippocampus during the early
      reperfusion period, even 3 h and 24 h after ischemia. There was no significant
      alteration in angiotensinogen mRNA level 3 h or 24 h after ischemia. These
      results suggest that the transient upregulation of AT2 receptor mRNA occurs in
      the cortex and hippocampus after injury and these changes may be in some way
      related to the molecular events which lead to delayed neuronal cell death.

PMID- 9004257
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP38) modulates lymphocyte
      and macrophage functions: stimulation of adherence and opposite effect on
      mobility.
AB  - The effects of pituitary adenylate cyclase-activating polypeptide (PACAP38) in a
      concentration range from 10(-13) to 10(-6) M were studied, in vitro, on two
      functions of peritoneal rat lymphocytes and macrophages: adherence and mobility
      (spontaneous and chemotaxis). The results show that PACAP38 raised the adherence
      of the two cell types, increased the mobility of macrophages and decreased the
      mobility of lymphocytes. The maximal effects were observed at 10(-10) M in
      macrophages and at 10(-9) M in lymphocytes. Moreover, incubation with increasing
      concentrations of phorbol myristate acetate (PMA), a protein kinase C (PKC)
      activator, resulted in a progressive enhancement of adherence and chemotaxis of
      both macrophages and lymphocytes. In contrast, retinal, a PKC inhibitor,
      significantly decreased these capacities. Incubation of macrophages with both PMA
      and PACAP38 did not have a synergistic effect on chemotaxis and adherence
      whereas, with lymphocytes, adherence was increased and chemotaxis was partially
      decreased. On the other hand, incubation with forskolin (an enhancer of
      intracellular cyclic AMP [cAMP] levels) caused inhibition and stimulation of
      chemotaxis and adherence, respectively, in both cell types. PACAP38 prevented the
      inhibitory effect of forskolin on chemotaxis of macrophages but not of
      lymphocytes, whereas the simultaneous presence of PACAP38 and forskolin was
      synergistic for adherence of both peritoneal cells. In addition, PACAP38 was
      chemoattractant for macrophages but not for lymphocytes. Furthermore, a VIP
      receptor antagonist was able to partially reverse the modulatory effects of
      PACAP38 on lymphocytes, but not on macrophages. These data suggest that PACAP38
      exerts its action through the binding to type I PACAP receptors and PKC
      activation in macrophages and through the elevation of intracellular cAMP levels
      by binding to type II PACAP receptors in lymphocytes. The present work reveals an
      additional link between neuropeptides and the immune system and suggests that the
      peptide PACAP modulates the immunological function of macrophages and
      lymphocytes.

PMID- 9004259
TI  - The molecular biology of preprotachykinin-A gene expression.
AB  - The expression of neuropeptides is largely tissue-specific and under strictly
      regulated and complex control. In view of the diversity of neuronal phenotypes,
      with concomitant plasticity of gene expression within any phenotype, it is
      obvious that there is coordinated activation and repression of genes. One of the
      central observations from these studies is that neuropeptide gene expression is
      dependent upon the combinatorial interaction of multiple transcription factors
      with the regulatory elements which determine mRNA synthesis. These factors
      mediate both tissue specific and stimulus inducible gene expression. We will
      illustrate some of the mechanisms that regulate neuropeptide gene expression
      utilizing our own studies on the rat preprotachykinin-A gene (rPPT) and, where
      appropriate, expand on the generality of these findings to other neuropeptide
      genes.

PMID- 9004269
TI  - Nonadrenergic relaxation of the cat cervical trachea evoked by stimulation in the
      lateral hypothalamic area.
AB  - The purpose of this study was to evaluate hypothalamic contributions to control
      of tracheal tone. We found hypothalamic sites where electrical stimulation (60-90
      microA: 1 ms pulse duration: 50 Hz: 5-10 s) and microinjection of L-glutamate (5
      50 nmol) produced tracheal relaxation responses along with decreased blood
      pressure and heart rate in anesthetized, spontaneously breathing cats. Responsive
      sites were located in anterior (LHAa) and tuberal (LHAt) regions of the lateral
      hypothalamic area indicating that neuronal cells in those regions are responsible
      for development of tracheal relaxation. In a second experiment, we evaluated
      possible pathways mediating the tracheal relaxation response elicited by LHA
      stimulation. Tracheal relaxation was not attenuated by beta-adrenergic blockade
      (propranolol i.v., 0.2-0.5 mg/kg); the response is mediated by nonadrenergic
      mechanisms Muscarinic blockade (atropine i.v.) at doses of 0.05-0.1 mg/kg almost
      abolished tracheal tone during spontaneous breathing, and LHA stimulation evoked
      a small, insignificant reduction of tracheal tone. Cervical vagotomy completely
      abolished the trachea tone, and LHA stimulation no longer evoked the tracheal
      relaxation. These results indicate the existence of a nonadrenergic descending
      pathway within the vagal efferents, which is linked with behavioral control
      arising from LHA, and causes trachea relaxation.

PMID- 9004270
TI  - GABAergic characteristics of transcallosal activity of cat motor cortical
      neurons.
AB  - GABAergic characteristics of transcallosal activity of cat pyramidal tract
      neurons (PTNs) and non-PTNs (nPTNs) were studied with stressing on GABAB
      receptors. PTNs and nPTNs were further classified into group 1 (< 10 ms) and
      group 2 (> 10 ms) based on the latency upon transcallosal stimulation. However,
      mainly the results of group 1 neurons were presented here, due to the small
      number of group 2 neurons. GABA, bicuculline, CGP 35348 and phaclofen were
      iontophoretically applied. The spike number to 20 trials of transcallosal
      stimulation was 8.9 +/- 4.3 (mean +/- S.D.) for group 1 PTNs (n = 14) and 10.4 +/
      4.5 for group 1 nPTNs (n = 38) under the control conditions. CGP 35348,
      phaclofen and bicuculline significantly increased the spike numbers in both
      cases. The increase was greater for nPTNs than for PTNs. GABA decreased them. The
      transcallosal latency was 3.9 +/- 1.1 ms for PTNs under the control conditions.
      CGP 35348, phaclofen and bicuculline significantly shortened the latency, and
      GABA elongated it. The transcallosal latency for nPTNs under the control
      conditions was 2.7 +/- 1.2 ms. This was significantly shortened by application of
      CGP 35348, phaclofen or bicuculline. GABA restored it. In conclusion, CGP 35348,
      phaclofen and bicuculline increased spike discharge and shortened the latency
      upon transcallosal stimulation for both group 1 PTNs and nPTNs.

PMID- 9004272
TI  - Synaptic connections of Purkinje cell axons with nucleocortical neurones in the
      cerebellar medial nucleus of the rat.
AB  - The cerebellar nucleocortical neurones may be part of a cortico-nucleocortical
      loop. It has not yet been demonstrated, however, whether they are directly
      afferented by Purkinje cell axons. This question has been addressed by using
      electron microscopic methods. WGA-HRP injections into the cerebellar vermis
      anterogradely labelled Purkinje cell terminals and retrogradely labelled
      nucleocortical neurones of the nucleus medialis. Postembedding GABA
      immunolabelling was used to double-labelled PC terminals and identified the GABA
      immunoreactive nuclear neurones. Of the identified nucleocortical neurones, the
      majority were immunonegative, but a few were GABA-immunoreactive. Both types were
      in synaptic contact with identified Purkinje cell terminals.

PMID- 9004271
TI  - Modified N-methyl-D-aspartate receptor subunit expression emerges in reeler
      Purkinje cells after accomplishment of the adult wild-type expression.
AB  - In terms of gene expression for the N-methyl-D-aspartate (NMDA) receptor channel
      subunits, the adult reeler cerebellum contains two Purkinje cell populations, one
      expressing the zeta 1 subunit mRNA (wild-type expression) and another expressing
      the epsilon 1 and zeta 1 subunit mRNAs (modified expression). To clarify
      development of these two populations, in situ hybridization analysis was
      performed in the reeler cerebellum from birth to 1 year of age. The epsilon 1
      subunit mRNA was not detected in any Purkinje cell clusters (PCCs) until
      postnatal day 21 (P21). Additional signals for the epsilon 1 subunit mRNA first
      appeared at P56 in a subset of PCCs, and persisted until 1 year of age. The
      epsilon 2 and epsilon 4 subunit mRNAs were transiently expressed in PCCs at
      birth, and disappeared thereafter. No signals for the epsilon 3 subunit mRNA was
      detected in PCCs at any postnatal stages examined. The zeta 1 subunit mRNA was
      expressed in all PCCs from birth through 1 year. When compared with the wild-type
      Purkinje cells, reeler Purkinje cells with modified expression are thus
      differentiated from those once accomplished the adult wild-type expression (the
      zeta 1 subunit alone) by down-regulation of the epsilon subunits. The present
      results further indicate that the onset of the modified expression is subsequent
      to the establishment of synaptic connectivities in the cerebellum.

PMID- 9004273
TI  - Nerve growth factor (NGF) induces increase in multi-ubiquitin chains and
      concomitant decrease in free ubiquitin in nuclei of PC12h.
AB  - Changes in Ubiquitin-immunoreactivity after nerve growth factor (NGF) treatment
      were investigated in PC12h cells. Ubiquitin-immunoreactivity was increased in the
      nucleus of NGF-treated cells. The quantitative analysis revealed that, after 7
      days of NGF treatment, almost 20% of cells had ubiquitin-immunoreactive nuclei
      and the frequency was increased thereafter. Levels of free ubiquitin and multi
      ubiquitin chains were measured by radioimmunoassay (RIA) and enzyme-linked
      immunosorbent assay (ELISA), respectively. Measurements were carried out for four
      subcellular fractions: urea- and water-soluble extracts of nuclei and cytoplasm.
      Decrease in free ubiquitin was observed in water-soluble cytoplasmic extracts of
      NGF-treated cells, though increase in multi-ubiquitin chains in the same fraction
      was not observed. As for nuclei, increase in multi-ubiquitin chains and
      concomitant decrease in free ubiquitin were found in the water-soluble extracts
      after NGF treatment. Levels of multi-ubiquitin chains did not change in urea
      soluble cytoplasmic extracts as well as nuclear urea-soluble ones after NGF
      treatment. These results indicated that multi-ubiquitination of nuclear proteins
      is increased during NGF-induced neuronal differentiation of PC12h cells.

PMID- 9004274
TI  - Sensory response properties of cortical neurons in the anterior ectosylvian
      sulcus of cats: intracellular recording and labeling.
AB  - Visual and auditory sensory responses of cortical neurons in the caudal half of
      the anterior ectosylvian sulcus (AES) of cats were examined under alpha
      chloralose anesthesia, using intracellular recording and labeling techniques.
      Stable intracellular recordings were obtained from 155 neurons, and 141 neurons
      exhibited responses to sensory stimuli. Of 141 sensory neurons, 74 (52%) were
      bimodal neurons that responded to both visual and auditory stimuli, and 67 (48%)
      were unimodal showing sensory responses only to visual (25) or auditory
      stimulation (42). Forty-five neurons (35 pyramidal neurons, 5 non-pyramidal
      neurons, 5 not classified) responsive to sensory stimuli were labeled with
      biocytin. The percentage of bimodal neurons of the biocytin-labeled neurons was
      40% (4/10) in layer II, 50% (10/20) in layer III-IV, 70% (7/10) in layer V and
      60% (3/5) in layer VI. Thus the convergence of visual and auditory inputs on
      single neurons was most intense in layer V. Auditory response latencies were in a
      narrow range from 10 to 40 ms, whereas visual response latencies were in a wide
      range from 15 to 100 ms. Late visual responses (> 60 ms) were more commonly
      elicited in biomodal neurons than in visual unimodal neurons. Visual responses in
      layer II were all elicited over 40 ms, whereas early visual responses within 40
      ms were observed in the other cortical layers. A subgroup of neurons (22/141) had
      a propensity to exhibit a burst discharge, a train of three to seven action
      potentials on a depolarizing envelope in response to sensory stimuli. Their
      specific distribution in cortical tissue was suggested by the result that six out
      of nine biocytin-labeled neurons (seven pyramidal neurons, two non-pyramidal
      neurons) showing burst discharges to sensory stimuli were observed in layer V.
      These results are considered to signify some aspects of intracortical
      organization related to the cross-modal integration of sensory inputs.

PMID- 9004275
TI  - Lactate spares glucose as a metabolic fuel in neurons and astrocytes from primary
      culture.
AB  - The effect of lactate on glucose metabolism in neurons and astrocytes from
      primary culture has been studied. The rates of glucose metabolism through the
      pentose-phosphate shunt, the pyruvate dehydrogenase-catalyzed reaction, the
      tricarboxylic acid cycle, the total lipogenesis and the synthesis of glycerol
      borne lipids in astrocytes were 2-3 fold higher than in neurons. However, the
      rate of glucose incorporation into sterols and esterified fatty acids was similar
      in both types of cells. Total glucose utilization was inhibited by lactate to the
      same extend in both neurons and astrocytes. Lactate strongly inhibited glucose
      oxidation through the pyruvate dehydrogenase-catalyzed reaction and the
      tricarboxylic acid cycle, in both neurons (60 and 44%, respectively) and
      astrocytes (64 and 62%, respectively). Glucose incorporation into sterols and
      fatty acids was also inhibited by lactate in both neurons and astrocytes (57 and
      76%, respectively) while the oxidation of glucose in the pentose-phosphate shunt
      and the synthesis of glycerol-borne lipids was not significantly affected. These
      results suggest that in the presence of lactate both neurons and astrocytes can
      utilize lactate as the major metabolic substrate, sparing glucose for the
      synthesis of NADPH(H+), ribose-5-phosphate and/or glycerol-borne lipids. An
      interaction between glucose and lactate metabolism at the level of the pyruvate
      dehydrogenase-catalyzed reaction is suggested.

PMID- 9004278
TI  - Vibration-induced finger flexion reflex and inhibitory effect of acupuncture on
      this reflex in cervical spinal cord injury patients.
AB  - The vibration-induced finger flexion reflex (VFR) and the inhibitory effect of
      acupuncture on this reflex were studied in five cervical spinal cord injury
      patients (C-SCIs). VFR, which is a tonic finger flexion reflex induced by
      vibratory stimulation on the finger tip, was induced before and after acupuncture
      was carried out on the same hand. A stainless steel needle was inserted to the
      Hoku point. As in healthy subjects, VFR was performed and it was significantly
      inhibited by acupuncture in the C-SCIs; mean maximum VFR was 204.2 +/- S.E. 68.6
      g before and 119.8 +/- S.E. 42.2 g after acupuncture. The present results suggest
      that at least part of the reflex center for VFR is located in the spinal cord and
      that part of VFR inhibition by acupuncture may be mediated via the spinal cord.

PMID- 9004277
TI  - Functional expression of GABA rho 3 receptors in Xenopus oocytes.
AB  - Homomeric rat GABA rho 3 receptors were expressed in Xenopus oocytes, and their
      pharmacological profile was investigated electrophysiologically. GABA activated
      the rho 3 receptors with an EC50 value of 7.5 microM and a Hill coefficient of
      1.6. The GABA-induced current was not antagonized by bicuculline (100 microM),
      but was blocked by picrotoxin (IC50: 0.68 microM for 100 microM GABA). The
      current was almost insensitive to pentobarbital, diazepam and a neurosteroid, 3
      alpha-OH-DHP. Many of the pharmacological properties of the rho 3 subunit were
      similar to those of the previously reported rat rho 1 and rho 2 subunits and
      GABAC receptors.

PMID- 9004276
TI  - Effects of coculture with the septum on the expression of long-term potentiation
      in organotypic hippocampal slice cultures.
AB  - The hippocampus receives major afferent innervation from the septum. Using
      organotypic slice culture, we investigated whether coculture with the septum
      would modulate transmission and plasticity of hippocampal synapses. In septo
      hippocampal cocultures, acetylcholinesterase-positive fibers extending from
      septal tissue to hippocampal slice were observed. Septo-hippocampal cocultures
      exhibited larger magnitude of long-term potentiation (LTP) in CA3 and CA1
      synapses than hippocampal slices cultured alone, without significant changes in
      maximal synaptic responses and macroscopic hippocampal cytoarchitecture.
      Unexpectedly, the facilitatory effect on hippocampal LTP was independent of
      afferent innervation from the septum, because (1) electrical stimulation of the
      cocultured septum suppressed the induction of hippocampal LTP, (2) chronic
      application of 1 microM atropine did not block the facilitatory effect, and (3)
      septo-hippocampal cocultures without contact with each other still showed a
      larger magnitude of LTP than hippocampal slices alone. These results suggest that
      diffusible factor(s) released from the septal tissue modulate functional
      maturation of hippocampal synapses as to the ability to support synaptic
      plasticity.

PMID- 9004279
TI  - The effects of ginkgolide B (BN52021) on guinea pig vestibular nucleus neurons in
      vitro: importance of controlling for effects of dimethylsulphoxide (DMSO)
      vehicles.
AB  - The present study investigated the effects of the platelet-activating factor
      (PAF) receptor antagonist, ginkgolide B, on guinea pig medial vestibular nucleus
      (MVN) neurons in vitro and addressed the potential problem of using
      dimethylsulphoxide (DMSO) as a solvent. Using DMSO as a solvent, 10(-10), 10(-8)
      and 10(-4) M ginkgolide B had no effect on extracellularly recorded MVN neurons
      in brainstem slices in vitro. Using 10(-6) M ginkgolide B, 50% (5/10) of MVN
      neurons exhibited a decrease in firing rate and 10% (1/10) of neurons responded
      with an increase in firing rate. While attempting to control for possible DMSO
      vehicle effects, 40% (4/10) of MVN neurons displayed a decrease in firing rate
      when ginkgolide B (10(-6) M) was presented before the DMSO control solution. When
      the DMSO vehicle was presented first, only 10% (1/10) responded similarly. In
      some cases the DMSO vehicle alone also produced a decrease in MVN neuron firing
      rate. These results emphasise the importance of using adequate DMSO control
      conditions in ginkgolide research.

PMID- 9004281
TI  - Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model.
AB  - Bone-seeking radiopharmaceuticals such as ethylenediaminetetramethylene
      phosphonate (EDTMP) complexes of samarium-153 and holmium-166 are receiving
      considerable attention for therapeutic treatment of bone metastases. In this
      study, using the baboon experimental model, multicompartmental analysis revealed
      that with regard to pharmacokinetics, biodistribution, and skeletal localisation,
      166Ho-EDTMP was significantly inferior to 153Sm-EDTMP and 99mTc-MDP. A more
      suitable 166Ho-bone-seeking agent should thus be sought for closer similarity to
      153Sm-EDTMP to exploit fully the therapeutic potential of its shorter half-life
      and more energetic beta radiation.

PMID- 9004280
TI  - 99mTc-2GAM: a tracer for renal imaging.
AB  - We propose a renal imaging agent, the 99mTc complex of the bidentate-N,S chelate
      N-(mercaptoacetyl)glycine (99mTc-2GAM), with the imaging characteristics of 99mTc
      DMSA but a faster kidney uptake; chemical evidence supports the formulation of
      99mTc-2GAM as [Tc(v)(O)(GAM)2]-. After biodistribution and toxicity studies in
      animals, 99mTc-2GAM was evaluated in five normal volunteers. 99mTc-2GAM is
      rapidly cleared from the blood (t1/2 = 9 min) and 50% of the ID is excreted in
      the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases
      up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each
      kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No
      significant activity is detected in other organs. We showed no differences
      between 99mTc-2GAM and 99mTc-DMSA compared in three patients with unilateral
      kidney disease. We conclude that 99mTc-2GAM has good practical and dosimetric
      features for renal imaging.

PMID- 9004282
TI  - Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro
      evaluation for PET imaging.
AB  - Hypoxic accumulation of 2-[5,6-3H]fluoro-2-deoxy-D-glucose ([3H]FDG),L-[methyl
      3H] methionine ([3H]MET), and L-[1-3H]leucine ([3H]LEU) was evaluated in two cell
      lines (UT-SCC-5 and UT-SCC-20) obtained from patients with squamous-cell
      carcinoma of the head and neck. Both cell lines were exposed to decreasing oxygen
      atmosphere (20%, 1.5%, or 0% O2) for 6 h, after which they were incubated for a
      further 1 h with tritiated FDG, MET, or LEU. An anoxic atmosphere resulted in a
      mean increase of [3H]FDG uptake of 120% and 46% over a baseline 20% oxygen
      atmosphere for UT-SCC-5 and UT-SCC-20A, respectively. Both total and acid
      precipitable [3H]MET uptake remained unchanged at 0% versus baseline, whereas
      acid-precipitable [3H]LEU uptake decreased by 46% for UT-SCC-5 and by 34% for UT
      SCC-20A at 0% O2. Our findings demonstrate that [3H]FDG accumulation is increased
      in hypoxic UT-SCC cell lines probably through activation of the metabolic steps
      associated with the glycolytic pathway. The decrease in acid-precipitable [3H]LEU
      uptake in hypoxia may indicate a decline in protein synthesis, whereas the
      unchanged [3H]MET uptake probably reflects the unaffected amino acid transport
      and slow incorporation of radiolabeled methyl group of MET in tumor proteins and
      nucleic acids. FDG and LEU, but probably not MET, warrant additional study as
      hypoxia-avid or hypoxia-reduced tracers for assessment of treatment effects
      designed to modify hypoxia.

PMID- 9004283
TI  - Influence of technetium-99m-labeling conditions on physico-chemical and related
      biological properties of an acylated poly-galactosidic macrophage targeting agent
      for inflammation imaging.
AB  - The potential of 99m-Tc-J001 for the investigation of inflammatory lesions via
      the targeting of recruited macrophages (M phi) has already been documented in
      several experimental models and in human diseases. To achieve a functional
      imaging of inflammation via M phi targeting, minimal labeled colloid content and
      high in vivo stability of 99mTc-J001 are essential. The actual specificity of
      such scintigraphy is closely dependent upon the radiolabeling of only the J001
      molecules available for M phi targeting. To develop an appropriate
      radiopharmaceutical kit, optimization of the labeling conditions was achieved
      from a series of pilot formulations that were evaluated for radiolabeling
      efficiency and both in vitro and in vivo 99mTc-J001 stability. Colloids were
      characterized using autocorrelation spectroscopy and multiangle laser-light
      scattering, radioactive colloid content of the formulations being deduced from
      biodistribution studies. This work has made possible the definition of a
      formulation exhibiting a radiolabeling yield > 97.0%, associated with in vivo
      stability and minimal colloid formation, thus greatly enhancing the specificity
      of such macrophage scintigraphy.

PMID- 9004285
TI  - Improved synthesis of beta-CIT and [11C]beta-CIT labeled at nitrogen or oxygen
      positions.
AB  - The important radiotracer precursor 2 beta-carbomethoxy-3 beta-(4-idophenyl)
      tropane (beta-CIT, RTI-55) was made in 52% overall yield from cocaine. Key steps
      were improved conjugate Grignard addition to anhydroecgonine methyl ester with >
      3.5:1 2 beta: 2 alpha-isomer selectivity, and a mild new direct aromatic
      iodination with I2 and silver triflate in CH2Cl2. The [11C]beta-CIT was labeled
      at either the N or O positions with [11C]methyl triflate; and efficient reversed
      phase HPLC was used to preparatively separate [N-11C]beta-CIT from N-nor-beta-CIT
      for the first time, and a fast solid-phase extraction (SPE) method was applied to
      preparatively separate [O-11C]beta-CIT from beta-CIT-acid precursor.

PMID- 9004284
TI  - Copper radionuclides and radiopharmaceuticals in nuclear medicine.
AB  - The chemistry, radiochemistry, radiobiology, and radiopharmacology of
      radiopharmaceuticals containing copper radionuclides are reviewed. Copper
      radionuclides offer application in positron emission tomography, targeted
      radiotherapy, and single photon imaging. The chemistry of copper is relatively
      simple and well-suited to radiopharmaceutical application. Current
      radiopharmaceuticals include biomolecules labelled via bifunctional chelators
      primarily based on cyclic polyaminocarboxylates and polyamines, and pyruvaldehyde
      bis(N4-methylthiosemicarbazone) (PTSM) and its analogues. The chemistry of
      copper, of which only a fraction has yet been exploited, is likely to be applied
      more fully in the future.

PMID- 9004286
TI  - Influence of a 99mTcN core on the biological and physicochemical behavior of
      99mTc complexes of L,L-EC and L,L-ECD.
AB  - 99mTc-nitrido complexes of L,L-ethylene dicysteine (99mTcN-L,L-EC) and 99mTcN-L,L
      ethylene dicysteine diethylester (99mTcN-L,L-ECD) were prepared and their
      characteristics compared to those of the respective 99mTc-oxo complexes. 99mTcN
      L,L-EC and 99mTcO-L,L-EC migrate to similar extents during electrophoresis at pH
      12, but, at pH6, 99mTcN-L,L-EC migrates further than 99mTcO-L,L-EC. Renal
      excretion of 99mTcN-L,L-EC is inferior to that of 99mTcO-L,L-EC, indicating that
      the TcN-glycine sequence has lower affinity for the renal tubular system. Both
      99mTcO-L,L-ECD and 99mTcN-L,L-ECD are neutral, but 99mTcN-L,L-ECD is hydrophilic
      and shows minimal brain uptake in both mice and the baboon.

PMID- 9004287
TI  - 18F-labeling and biodistribution of the novel fluoro-quinolone antimicrobial
      agent, trovafloxacin (CP 99,219).
AB  - [18F]CP 99,219 [(1 alpha, 5 alpha, 6 alpha)-7-(6-amino-3-azabicyclo [3.1.0]hex-3
      yl)-1-(2,4-difluorophenyl)-6-fluoro-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3
      carboxylic acid] was prepared by 18F for 19F exchange followed by reverse-phase
      HPLC purification. Studies of the effects of reaction time and temperature on 18F
      incorporation demonstrated that heating 1.0 mg of CP 99,219 in 0.5 cc of DMSO
      with 4.5 mg of K2CO3 and 24 mg of Kryptofix for 15 min at 160 degrees C results
      in the optimal compromise between radiochemical yield and purity. This method
      routinely provides radiochemical yields of 15-30% [EOS] with radiochemical
      purities of > 97%. Varying the concentration of CP 99,219 in the reaction mixture
      had no effect on yield. Biodistribution studies in rats demonstrated that
      significant concentrations of drug accumulate in most tissues. The tissues with
      the highest concentrations of drug were intestine, liver, kidney, and stomach.

PMID- 9004288
TI  - Radiosynthesis of [18F] N-3-fluoropropyl-2-beta-carbomethoxy-3-beta-(4
      iodophenyl) nortropane and the first human study with positron emission
      tomography.
AB  - A procedure for the routine preparation of [18F]FP-CIT has been developed.
      Purification of the final product was achieved by preparative HPLC using
      phenethyl column without decomposition or epimerization. [18F] labeled-N
      fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl) nortropane was prepared
      and PET imaging was performed on human subjects. A high uptake into striatal
      regions was observed. HPLC plasma analysis using [18F]FP-CIT indicated the
      presence of only one metabolite. By directly comparing the behavior of these
      three radiotracers ([18F]DOPA, [123I]FP-CIT, and [18F]FP-CIT) in the same
      subjects, we can enhance our understanding of the dopaminergic system as well as
      the relative potential of these techniques in a clinical research setting.

PMID- 9004289
TI  - A high-yield and simplified procedure for the synthesis of alpha-[11C]methyl-L
      tryptophan.
AB  - Alpha-[11C]methyl-L-tryptophan (AMT) has been synthesized by stereoselective
      methylation with [11C]methyl iodide of the lithium-enolate generated by treating
      dimethyl 2(S), 3a(R), 8a(S)-(+)-hexahydro-8(phenylsulfonyl)pyrrolo [2, 3-b]indole
      1,2-dicarboxylate (2) with lithium diisopropyl amide (LDA) at -55 degrees C,
      followed by ring opening using trifluoroacetic acid and alkaline hydrolysis of
      the protecting groups. The crude product was purified by a simple reverse-phase C
      18 Sep-Pak procedure. The purified product was isolated with an average
      radiochemical yield of 53 +/- 12% (decay corrected) in 30-35 min from [11C]methyl
      iodide. At end of synthesis (EOS), 138 +/- 35 mCi (n = 24) of product was
      collected with a specific activity of ca. 1-1.3 Ci/mumol (EOS) (4-5 Ci/mumol @
      EOB) starting from 1.5 Ci (EOB) of [11C]CO2.

PMID- 9004290
TI  - [1-11C]octanoate as a potential PET tracer for studying glial functions: PET
      evaluation in rats and cats.
AB  - To evaluate the ability of [1-11C]octanoate as a PET tracer for imaging the
      brain, we examined its distribution in the brain and surrounding tissues in rats
      and cats with PET. In rats, owing to the accumulated radioactivity in the
      harderian glands, clear brain images were not obtained at rostral levels. In
      cats, the brain was imaged clearly at every level of the coronal brain slices,
      suggesting the potential of [1-11C]octanoate for imaging the brain.

PMID- 9004291
TI  - Preparation of radioactive lead complexes utilizing Chelex methodology.
AB  - The use of Chelex resin for the synthesis of radioactive lead complexes has been
      explored. The process involved immobilization of 203Pb on the resin and
      subsequent elution of complexed lead by chelating agents. 203Pb complexes derived
      from meso- and racemic dimercaptosuccinic acid (meso-DMSA, rac-DMSA) were
      prepared and assessed for stability in vitro.

PMID- 9004292
TI  - The effect of cyclosporine-A on labeling blood cells with radiopharmaceuticals.
AB  - The effect of cyclosporine-A (CsA) on the labeling efficiencies of red blood
      cells with reduced 99mTcO4-; leukocytes and platelets with 111In oxine was
      studied. Blood was used from rats treated with CsA (30 mg/kg body weight) for 28
      consecutive days and from control rats. For 99mTc labeling of RBCs, blood was
      obtained from individual rats and in vitro labeling technique was used. For
      leukocyte and platelet labeling, blood was pooled from 5 rats either treated with
      CsA or control. Leukocytes/platelets were labeled with 111In oxine using routine
      techniques. The labeling efficiency for 99mTc RBCs was 83.42 +/- 0.83% (CsA
      treated) and 84.85 +/- 0.62% (control); 111In-oxine leukocytes was 38.5 +/- 1.75%
      (CsA treated) and 42.5 +/- 3.53% (control); and for 111In-oxine platelets, it was
      74.0 +/- 2.5% (CsA treated) and 78.0 +/- 1.41% (control). Comparison of the
      results indicate that there is no difference between the percent labeling
      efficiencies of 99mTc RBCs, 111In-oxine leukocytes, and 111In-oxine platelets for
      CsA-treated and control rats. Hence, CsA does not interfere with the labeling
      process of blood cells with radiopharmaceuticals.

PMID- 9004293
TI  - Methodological reappraisal of platelet radiolabelling with 111indium.

PMID- 9004294
TI  - Resuscitation following arrhythmia in patients undergoing
      pharmacological/exercise stress for myocardial perfusion imaging.

PMID- 9004295
TI  - Intra-operative nuclear medicine in surgical practice.
AB  - The use of radionuclides for the intra-operative localization of tumours has
      increased steadily over the past 15 years. We reviewed more than 15 years
      experience of a peripatetic service using a sterilizable probe system in
      operating theatres throughout the UK for localizing bone and soft tissue lesions.
      The technique requires the positive concentration of an appropriate
      radiopharmaceutical, together with a suitably designed detector system which can
      be sterilized for use during surgery. All surgical procedures were undertaken
      following initial positive imaging studies. A well-collimated nuclear probe with
      a 5 mm diameter CdTe detector was sterilized with ethylene oxide gas and coupled
      to a digital counter and ratemeter for use in the operating theatre. A total of
      68 surgical procedures have been undertaken at 35 hospitals. Fifty-eight patients
      underwent excision of osteoid osteoma subsequently proven by histology. The other
      lesions successfully resected included osteoblastoma, hamartoma, Brodie's
      abscess, chronic bone infection, ectopic parathyroid adenoma and metastatic
      neuroblastoma. The technique can now be regarded as the method of choice for the
      surgical localization of osteoid osteoma. The successful detection of lesions at
      surgery can be assured providing that clear localization of the
      radiopharmaceutical occurs on the pre-operative images. The intra-operative use
      of conventional and new tumour-specific radiopharmaceuticals is reviewed and we
      confirm an increasing role for the surgical-probe-guided localization of primary
      and metastatic tumours.

PMID- 9004296
TI  - 99Tcm-DTPMP as a skeletal scintigraphy agent: distribution in rats in comparison
      with 99Tcm-MDP.
AB  - The distribution and elimination of 99Tcm-complexes with methylene-diphosphonate
      (MDP) and with the calcium salt of diethylene-triamine-penta(methylene
      phosphonate) (DTPMP) were compared in rats. Both compounds exhibited high bone
      uptake and long-term retention of radioactivity in the skeleton. No significant
      accumulation of the complexes in non-osseous tissues was found. The
      pharmacokinetics of both chelates were similar, small differences in their
      distribution and elimination probably being due to different binding to plasma
      proteins. Two processes, namely bone uptake and kidney elimination, contributed
      to the disappearance of the complexes from the blood. The higher protein binding
      of 99Tcm-MDP probably caused its slower rate of urine elimination and
      insignificantly higher bone uptake compared with 99Tcm-DTPMP. On the other hand,
      the more rapid reduction in blood and muscle radioactivity with 99Tcm-DTPMP
      resulted in accelerated non-osseous tissue clearance compared with 99Tcm-MDP.
      This suggests that the time between administration and imaging may be shorter for
      99Tcm-DTPMP than for 99Tcm-MDP. Furthermore, the much greater stability of 99Tcm
      DTPMP may also reduce degradation of the complex and 99Tcm liberation in the
      body. For a general evaluation of both compounds, it will be necessary to
      determine lesion-to-bone ratios.

PMID- 9004297
TI  - Cerebral blood flow imaging in paediatrics: a review.
AB  - The ability to study regional cerebral blood flow (rCBF) is available in many
      institutions, especially with the spread of multi-headed gamma cameras. The use
      of this technique in paediatrics requires special attention to detail in the
      manner of data acquisition and handling the child. The interpretation of the rCBF
      study in a child requires knowledge of normal brain maturation. The major
      clinical use in paediatrics is epilepsy because of the advances in surgery and
      the frequency of complex partial seizures. Other indications in paediatric
      neurology include brain death, acute neurological loss including stroke, language
      disorders, cerebral palsy, hypertension due to renovascular disease, traumatic
      brain injury and migraine. There are paediatric psychological conditions in which
      rCBF assessment has been undertaken, including anorexia nervosa, autism, Gilles
      de la Tourette Syndrome (GTS) and attention deficit disorder-hyperactivity
      (ADHD). This article attempts to review all aspects of rCBF studies in
      paediatrics.

PMID- 9004298
TI  - Clinical evaluation of the bone marrow imaging agent 99Tcm-phytate in the
      detection of bone metastases.
AB  - The aims of this study were to assess whether 99Tcm-phytate can detect metastatic
      skeletal lesions, and to compare it with 99Tcm-methylene diphosphonate (99Tcm
      MDP) and 99Tcm-labelled human serum albumin nanocolloids (99Tcm-NC). Twenty-four
      patients with multiple bony metastases, investigated by 99Tcm-MDP whole-body
      scintigraphy, underwent 99Tcm-phytate bone marrow imaging. A separate bone marrow
      scintigram with 99Tcm-NC was performed in 20 of the patients. All of the
      metastatic lesions detected on the 99Tcm-phytate scintigrams exhibited photon
      abundant foci only. Most of the 99Tcm-phytate scintigrams detected fewer
      metastatic lesions than the corresponding bone scintigrams. Visual comparison of
      the 99Tcm-NC images showed that 13 of 20 99Tcm-NC images were superior to the
      99Tcm-phytate images in the detection of metastatic involvement of the skeleton.
      Thus 99Tcm-phytate should not be used as a bone marrow imaging agent for the
      detection of skeletal metastases.

PMID- 9004299
TI  - The influence of two bone agents (99Tcm-pyrophosphate and 99Tcm
      methylenediphosphonate) on quantitative sacroiliac joint scintigraphy.
AB  - Bone scintigraphy is an extremely sensitive method for the detection of focal
      bone disease. In many hospitals, quantitative sacroiliac joint scintigraphy is
      still a routine procedure in detecting sacroiliitis. In previous studies, both
      99Tcm-methylenediphosphonate (99Tcm-MDP) and 99Tcm-pyrophosphate have been used
      for bone imaging. 99Tcm-pyrophosphate is eliminated more slowly than 99Tcm-MDP
      from the circulation and gives a higher background activity. We wished to
      discover the sacroiliac/sacral ratio (SI/S ratio) changes when using different
      bone agents. The aim of this study was to evaluate differences in SI/S ratios
      between the two bone agents. Forty-six control subjects, aged 31-50 years, with
      no history of back pain, scoliosis, kyphosis, joint pain, arthritis, lesions
      within the pelvis, chemotherapy or systemic diseases such as diabetes or systemic
      lupus erythematosis, were included in the study. A posterior planar image of the
      pelvis was performed to calculate the SI/S ratio 3 h after the injection of 740
      MBq 99Tcm-MDP or 99Tcm-pyrophosphate. Twenty-five subjects were studied with
      99Tcm-MDP and 21 with 99Tcm-pyrophosphate. We found the SI/S ratios using 99Tcm
      MDP to be slightly higher than those using 99Tcm-pyrophosphate, especially on the
      left side, but this difference was not statistically significant (P-values > 0.1
      on both sides using Student's t-tests for unpaired data).

PMID- 9004300
TI  - Determination of left ventricular cardiac volume by simultaneous radionuclide
      angiography and measurement of oxygen consumption at rest and during maximal
      exercise: a comparison of two non-invasive isotopic procedures.
AB  - The investigation of left ventricular contractile reserve usually requires the
      determination of left ventricular volume, but its measurement with radionuclide
      angiography is difficult. The aim of this study was to determine left ventricular
      volume directly during exercise by the simultaneous measurement of peak exercise
      left ventricular ejection fraction (LVEF) and oxygen consumption (VO2max) and to
      compare the results with another geometric method. In the absence of lung
      disease, the systemic arteriovenous oxygen difference (DAVmax) during maximal
      exercise converges to 0.13-0.14 ml O2 per ml blood. The measurement of VO2max
      allows maximal cardiac output (COmax) to be calculated as VO2max = COmax. DAVmax.
      By simultaneously determining LVEFex, exercise end-diastolic volume (EDVex) can
      then be expressed as a linear function of VO2max, maximal heart rate (HRmax),
      DAVmax and LVEFex. Then, the relationship between end-diastolic counts and true
      volume can be derived at rest. The two methods were closely correlated (r = 0.91,
      P < 0.001), despite the geometric method being less accurate when applied to low
      counting statistic acquisitions. We conclude that rest and exercise left
      ventricular volume can be determined non-invasively by the simultaneous
      measurement of VO2max and LVEFex. Furthermore, this method provides additional
      prognostic information which is clinically relevant in the staging of patients
      with heart failure.

PMID- 9004301
TI  - Vasoreactive effect of acetazolamide as a function of time with sequential PET
      15O-water measurement.
AB  - The accurate assessment of vascular flow reserve is crucial for the evaluation of
      risk among patients with cerebrovascular disease. In six patients with unilateral
      occlusion of the internal carotid artery and one patient with unilateral
      occlusion of the middle cerebral artery (mean +/- S.D. age = 68 +/- 3 years), we
      measured cerebral blood flow (CBF) after the administration of 940 MBq 15O-water
      using a remotely controlled power injector. Studies were performed at rest, after
      10 min, and then 10, 20 and 30 min after the administration of 1 mg acetazolamide
      to evaluate the vasoreactive effect, as reflected by an increase in CBF. Sixteen
      regions of interest (ROIs) were drawn over the CBF images. These ROIs were as
      follows in each hemisphere: Area I, four areas in the cortical middle cerebral
      arterial territory (superior frontal, frontal, temporal and parietal areas); Area
      II, four areas of the deep middle cerebral and vertebral arterial territory
      (occipital area, basal ganglia, thalamus and cerebellum). Taking normalized
      resting CBF to be 100%, the mean CBF measured 10, 20 and 30 min post-injection
      using sequential positron emission tomography was as follows: Area I, 141.4 +/-
      16.3, 127.7 +/- 15.3 and 128.2 +/- 17.4% for non-occluded sites and 116.3 +/-
      22.8, 112.7 +/- 16.4 and 114.9 +/- 17.1% for occluded sites; Area II, 143.4 +/-
      14.5, 126.2 +/- 10.4 and 125.0 +/- 12.9% for non-occluded sites and 141.9 +/-
      28.9, 126.0 +/- 20.5 and 124.1 +/- 17.1% for occluded sites. A significant
      difference in mean CBF was noted between the non-occluded and occluded sites in
      Area I, the most marked difference of 25.1% being observed 10 min after the
      administration of the acetazolamide. We conclude that for an accurate assessment
      of vascular reserve in patients with cerebrovascular disease, CBF should be
      measured 10 min post-administration of the acetazolamide.

PMID- 9004302
TI  - Glucose metabolism and pathological findings in uveal melanoma: preliminary
      results.
AB  - The aims of this study were to assess the sensitivity of positron emission
      tomography (PET) using [18F]fluorodeoxyglucose (18F-FDG) in the detection of
      uveal melanoma, and to establish the relationship between pre-operative 18F-FDG
      uptake and a number of pathological features of uveal melanoma. Twenty
      consecutive patients with a clinical diagnosis of uveal melanoma were enrolled in
      the study. 18F-FDG uptake was assessed in all subjects and the following
      parameters were assessed in 11 enucleated subjects: the mitotic index, the MIB-1
      proliferating cell index, number of epithelioid cells, largest tumour diameter,
      tumoral necrosis and inflammatory infiltration. Tumours with a diameter less than
      7.5 mm were not detected by PET, possibly because of limited spatial resolution,
      and only 7 of 12 tumours with a diameter greater than 7.5 mm were detected. With
      tumours greater than 7.5 mm in diameter, PET and 18F-FDG allow two subgroups to
      be distinguished: those with high and those with low glucose consumption. Apart
      from tumour size, 18F-FDG uptake was not related to the pathological features
      examined. We hypothesize that 18F-FDG uptake may be related to the ratio of
      viable to non-viable cells, or to the hypoxic cell fraction within the tumour.

PMID- 9004303
TI  - Imaging of beta-oxidation by static PET with 14(R,S)-[18F]-fluoro-6
      thiaheptadecanoic acid (FTHA) in patients with advanced coronary heart disease: a
      comparison with 18FDG-PET and 99Tcm-MIBI SPET.
AB  - 14(R,S)-[18F]-fluoro-6-thiaheptadecanoic acid (FTHA) has been proposed as a PET
      tracer of the beta-oxidation pathway. The aim of this study was to investigate
      the diagnostic value of FTHA using static PET imaging in patients with
      ischaemically reduced left ventricular function. Twenty-one patients with
      angiographically proven advanced coronary heart disease were examined. All
      patients underwent SPET with 400 MBq [99Tcm]-2-methoxy-isobutyl-isonitrile (MIBI)
      for perfusion assessment and PET with 250 MBq FTHA under fasting conditions and
      with 150 MBq 2-[18F]-fluoro-2-deoxyglucose (FDG) following an oral glucose load.
      The uptake of FTHA and FDG was analysed quantitatively in 33 regions. Regional
      uptake was normalized to the region with highest MIBI uptake and expressed as a
      percentage. FTHA uptake paralleled MIBI uptake (r = 0.80) but not FDG uptake (r =
      0.57). Mean FTHA uptake (38.1 +/- 16.3%) in 190 regions with severely reduced
      perfusion (MIBI uptake < 50%, mean uptake 36.8 +/- 9.4%) was significantly lower
      compared to FDG uptake (54.6 +/- 25.0%). FTHA uptake was preserved (> or = 70%)
      in 8 of 52 (13%) regions only with severely reduced perfusion but preserved
      glucose metabolism (FDG uptake > or = 70%). The similarity between FTHA and MIBI
      uptake suggests that static PET imaging with FTHA is of limited value when
      distinguishing between ischaemic or hibernating myocardium and scar. The
      underestimation of viability may be caused both by the dependence of uptake on
      flow and the suppression of beta-oxidation in regional chronic ischaemia under
      fasting conditions.

PMID- 9004304
TI  - Reproducibility of simplified techniques for the measurement of 51Cr-EDTA
      clearance.
AB  - The aim of this study was to assess the reproducibility of a number of simplified
      clearance methods using chromium-51 ethylenediamine tetraacetic acid (51Cr-EDTA)
      and to compare these with the multiple blood sample technique. Twenty-four
      healthy volunteers were enrolled into the study. The test was performed twice, 1
      week apart and under similar physiological conditions. After intravenous
      injection of the tracer, 13 blood samples were taken between 5 and 240 min. The
      reference clearance was calculated after adapting a bi-exponential fit on the
      whole plasma disappearance curve. Simplified methods included the slope intercept
      method using different combinations of blood samples (2 and 4 h; 2, 3 and 4 h;
      1.5, 2, 3 and 4 h; 1.5, 2 and 3 h) and several single clearance methods
      (Constable 3 h; Groth 3 h; Groth 4 h). The standard deviation of the differences
      between the first and second measurements were similar for all methods,
      confirming the comparable reproducibility of these methods.

PMID- 9004305
TI  - 99Tcm-MAG3 renal studies: effective renal plasma flow in patients with spinal
      cord injuries.
AB  - To assess whether number of years since time of injury, level or degree of
      injury, gender or age influence renal function in patients with spinal cord
      injury (SCI), single and total kidney effective renal plasma flow (ERPF) was
      measured in 66 patients using 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3). In
      approximately 50% of the SCI patients, the single kidney ERPF was less than 250
      ml min-1 and total ERPF was less than 500 ml min-1. The single kidney ERPF was
      worse in female and older SCI patients than in male and younger patients. For
      total ERPF, age only was a significant factor. Total ERPF was worse in female
      than in male SCI patients, though this did not reach significance. We conclude
      that the non-invasive measurement of renal function using 99Tcm-MAG3 is safe and
      applied easily to SCI patients.

PMID- 9004306
TI  - Inter-observer agreement in the reporting of 99Tcm-DMSA renal studies.

PMID- 9004308
TI  - Assisted suicide: an agonizing ethical exception?

PMID- 9004309
TI  - A comparative analysis of primary care nurse practitioners and physician
      assistants.

PMID- 9004310
TI  - Demographic predictors of participation in free prostate cancer screening.

PMID- 9004311
TI  - Annual update of how each state stands on legislative issues affecting advanced
      nursing practice.

PMID- 9004312
TI  - Negotiating symbolic space: strategies to increase NP status and value.
AB  - Nurse practitioners (NPs) have an unprecedented opportunity to become key primary
      health care providers, yet barriers to independent practice still exist. The
      purpose of this research was to explore and describe the practice of NPs from
      their perspective. Open-ended, interactive interviews were conducted with 23 NPs.
      Data analysis using the grounded theory method revealed that NPs attempt to
      establish their roles from a marginalized position and are often subjected to
      psychological and structural discounting. To combat discounting, the NPs in this
      research worked to negotiate the symbolic space required for their acceptance as
      valued health care providers. They used techniques of cultivating, bargaining,
      confronting, and disengaging. All of these techniques promote NP role definition
      by generating and preserving role boundaries, thereby moving NPs toward the
      symbolic space necessary for them to become part of the national consciousness.
      This research contributes to clarification of the NP role and the building of a
      formal theory of advanced nursing practice.

PMID- 9004313
TI  - Acute bronchitis in adults: commonly diagnosed but poorly defined.
AB  - This article reviews the existing literature about acute bronchitis, a condition
      commonly diagnosed but poorly defined. The little epidemiologic research that has
      been done has failed to identify a microbiologic etiology approximately 60% to
      85% of the time. The majority of cases appear to be caused by viruses, but 25% of
      adults with nonspecific lower respiratory symptoms may actually have pertussis.
      Mycoplasma pneumoniae and Chlamydia pneumoniae probably play minor roles.
      Although clinicians frequently prescribe antibiotics to patients they have
      diagnosed with acute bronchitis, there is little evidence in support. General
      treatment studies have failed to demonstrate benefit, and the natural history of
      even potentially curable pathogens is not altered by antimicrobial therapy. Some
      recent studies suggest that albuterol may be the best treatment choice for acute
      bronchitis; it can successfully ameliorate symptoms, and does not pose the same
      public health risk as inappropriate antibiotics do. Erythromycin may occasionally
      be indicated for patients in frequent contact with small infants not yet
      immunized against pertussis, but careful surveillance of the child is probably
      more effective than treating the contagious adult.

PMID- 9004315
TI  - Annual review of newly approved drugs.

PMID- 9004314
TI  - Pediatric cardiovascular assessment and referral in the primary care setting.
AB  - Pediatric cardiovascular problems, although not common, have the potential to
      have significant associated morbidity and mortality if they go unrecognized. This
      article focuses on pediatric assessment techniques required to perform a
      comprehensive cardiovascular evaluation on an infant or an older child in the
      primary care setting. Specific key physical assessment parameters to be evaluated
      and a general developmental approach to the assessment of children are suggested.
      Auscultation of the pediatric heart is a main focus, including strategies in
      approaching children, a guide for organizing the ausculatory process, and
      differences between adult and pediatric heart sounds. Assessment of peripheral
      pulses, blood pressure, skin and mucous membrane color, and capillary refill are
      emphasized as an important aspect of comprehensive evaluation of the child's
      peripheral circulation. Criteria for referral are provided in terms of which
      children should be referred, who the referral should be made to, and the time
      frame in which the referral should be made.

PMID- 9004316
TI  - Nurse practitioners coordinate clinical trials.

PMID- 9004317
TI  - APN role with migrant population.

PMID- 9004320
TI  - A scaling analysis of measles epidemics in a small population.
AB  - We present a detailed analysis of the pattern of measles outbreaks in the small
      isolated community of the Faroe Islands. Measles outbreaks in this population are
      characterized by frequent fade-out of infection resulting in long intervals when
      the disease is absent from the islands. Using an analysis of the distribution of
      epidemic sizes and epidemic durations we propose that the dynamical structure
      observed in the measles case returns reflects the existence of an underlying
      scaling mechanism. Consequently the dynamics are not as purely stochastic as is
      usually thought for epidemiological systems of this sort. We use a lattice-based
      epidemic model to provide a theoretical estimate of the scaling exponents and
      show that a conventional compartmental SEIR model is unable to reproduce this
      result. The methods discussed in this paper are general and represent a novel way
      to consider the dynamics of any other communicable disease where there is
      frequent fade-out in the case returns.

PMID- 9004318
TI  - The genetical history of an isolated population of the endangered grey wolf Canis
      lupus: a study of nuclear and mitochondrial polymorphisms.
AB  - The grey wolf was thought to have been exterminated in the Scandinavian peninsula
      when the sudden appearance of a few animals in southern Sweden was reported in
      1980. These wolves founded a new Swedish population which currently numbers at
      least 25 individuals, one of the world's smallest populations of the species. The
      sudden occurrence of the founder animals caused speculation that these had not
      appeared by 'natural' means but rather were Swedish zoo animals deliberately
      released by man. To analyse if this was the case and to elucidate the genetic
      status of this small and isolated population, we assessed nuclear and
      mitochondrial (mt) genetic variability in wild and captive grey wolves, using
      microsatellite typing and sequence analysis of the mtDNA D-loop. The new
      population was found to be monomorphic for a mtDNA haplotype which also was
      present in the Swedish zoo population. A total of four different mtDNA haplotypes
      were found among all captive and wild wolves (including two animals from an
      occasional establishment of a few wolves in northern Sweden in the late 1970s),
      with a maximum sequence divergence of 3.1%. Despite the mtDNA congruence, animals
      from the zoo population could most likely be excluded as founders for the wild
      population since the latter group of animals displayed several unique
      microsatellite alleles (i.e. alleles not found in the zoo population). Moreover,
      a phylogenetic analysis of individual wolves, using microsatellite allele sharing
      as distance measure, placed all wild animals on a branch separated from that of
      the captive animals. The average degree of nuclear variability as well as allelic
      diversity was similar in the wild and the captive populations, respectively, but
      was lower than that reported for North-American populations of grey wolves.
      Polymorphism has declined in wild wolves born in recent years suggesting that
      this small population is currently suffering from a loss of genetic variability
      due to inbreeding. Inbreeding depression is documented in captive wolves and the
      long-term survival of the wild Swedish population may therefore depend on
      immigration of animals from Russia. This study illustrates the usefulness of
      microsatellites for dissecting close genetic relationships and for addressing the
      genetic status of individuals.

PMID- 9004321
TI  - On the elementary mechanism underlying secondary motion processing.
AB  - The movement of luminance-defined targets can be easily extracted by elementary
      motion detectors (EMDs) of the correlation type which often are referred to as
      Reichardt-detectors. In contrast to such 'primary motion', in 'secondary motion'
      the moving target is defined by more complex features, like changes in texture,
      flicker, or local contrast. Such stimulus attributes have to be extracted from
      the retinal intensity distribution by some nonlinear preprocessing, before they
      are fed into motion detectors. An intriguing case is the perception of the
      movement of the motion signal, as is present in theta motion, where an object
      moves in a different direction than the texture on its surface. A two-layer model
      of hierarchically organised EMDs has been postulated to account for such motion
      extraction. Other than for the first layer, the computational nature of the
      mechanism underlying motion processing in the second layer so far is a matter of
      speculation, and is therefore characterized here by means of computer simulations
      and psychophysical experiments. Random dot kinematograms were generated in which
      sinusoidally modulated vertical dot motion defined gratings, and coherence
      thresholds were measured for the direction discrimination of a horizontally
      travelling modulation function. This was done for a variety of spatial
      frequencies and speeds of the modulation sinusoid. Thresholds turn out to be
      lowest not for a particular speed, but for a fixed temporal frequency of the
      modulation function (about 1 cycle per second), when various combinations of fine
      and coarse, and fast and slow secondary gratings are tested. This result favours
      a correlation-type mechanism over a gradient-type scheme which should lead to a
      speed-optimum independent of spatial frequency.

PMID- 9004322
TI  - Nutrition in the undergraduate medical curriculum. The Stratford Executive Group.

PMID- 9004323
TI  - New insights into the development of obesity: obese genes and the leptin system.

PMID- 9004324
TI  - The role of altered sympathetic nervous system activity in the pathogenesis of
      obesity.

PMID- 9004325
TI  - Eating behaviour, food preferences and dietary intake in relation to obesity and
      body-weight status.

PMID- 9004326
TI  - Defects in substrate oxidation involved in the predisposition to obesity.

PMID- 9004327
TI  - The role of lifestyle in health: the epidemiology and consequences of inactivity.

PMID- 9004328
TI  - Screening for nutritional risk.

PMID- 9004329
TI  - The management of malnutrition in hospital.
AB  - Treatable malnutrition may occur in up to 25% of hospital patients, depending on
      the specialty concerned. Nutritional status may also deteriorate during a
      prolonged hospital stay. The management and prevention of malnutrition requires a
      climate in which hospital managers have a positive policy towards nutritional
      care, a screening system to identify the patients at risk, and appropriate
      protocols for action. Catering services need to be reorganized to address the
      problems of the sick, so that appropriate food is not only prepared but delivered
      in a way which makes it likely to be consumed. For the optimal management of
      artificial nutrition by the enteral or parenteral route, a skilled nutrition team
      is both necessary and cost-effective.

PMID- 9004330
TI  - The analysis of complex carbohydrates: relevance of values obtained in vitro.

PMID- 9004331
TI  - A physico-chemical perspective of plant polysaccharides in relation to glucose
      absorption, insulin secretion and the entero-insular axis.

PMID- 9004332
TI  - Fermentation of non-digestible oligosaccharides by human colonic bacteria.

PMID- 9004333
TI  - Anaerobic fungi in the digestive tract of mammalian herbivores and their
      potential for exploitation.

PMID- 9004334
TI  - The use of 14C-labelled substrates to study plant cell wall breakdown in the
      gastrointestinal tract.

PMID- 9004335
TI  - The role of butyrate in human colonic epithelial cells: an energy source or
      inducer of differentiation and apoptosis?

PMID- 9004336
TI  - The role of antioxidants in nutritional support.

PMID- 9004337
TI  - Psychopharmacologic violence associated with cocaine abuse: kindling of a limbic
      dyscontrol syndrome?
AB  - 1. An association of cocaine abuse with aggressive or violent behavior arising
      from direct pharmacologic effects of cocaine is demonstrable in the forensic and
      clinical literature. 2. The neurobehavioral basis for this association is
      considered form among known CNS actions of cocaine. A hypothesis is developed
      concerning the role of pharmacological kindling by cocaine that may sensitize for
      release of limbic-hypothalamic mechanisms of aggressive behavior, and for a drug
      induced dyscontrol syndrome. 3. Parallels are drawn to kindling by electrical
      stimuli, and to neurophysiological research on mechanisms of aggression. 4. A
      role of concurrent hyperthermic effects of cocaine is suggested. 5. Potential
      contributions of cocaine actions on CNS serotonergic, catecholaminergic and/or
      adenosinergic systems are considered. 6. A likely role of concurrent ethanol
      ingestion to enhance the manifestation of cocaine-associated violence is
      recognized. 7. Pharmacological challenges, lidocaine or caffeine, are suggested
      as a means of detecting lowered thresholds of limbic excitability as a
      consequence of repeated cocaine exposures.

PMID- 9004338
TI  - Cognitive and emotional deficits in early stages of HIV infection: an event
      related potentials study.
AB  - 1. In order to inventory different Event-Related Potentials (ERP) modifications
      in HIV-infection the authors have evaluated 23 HIV-positive subjects and 12 HIV
      negative subjects. ERP were recorded during an auditory oddball task. 2.
      Electrophysiological results showed that the latency of the N100 component of the
      ERP was significantly increased in HIV-positive subjects compared to the HIV
      negative subjects. The latency of the N200 component of the ERP showed a similar
      tendency which just failed to reach significance when considering HIV-positive
      subjects vs HIV negative subjects. This result was in agreement with the
      literature which reported increased latencies in HIV infection. 3. Considering
      all subjects the authors have observed a correlation between the amplitude of the
      P300 and the emotional deficit. This correlation was stronger in subjects who
      presented an emotional deficit and was independent of any other
      psychopathological symptom. 4. The use of ERP appeared to be a sensitive
      technique to detect subclinical manifestations in HIV asymptomatic subjects and
      therefore would help to identify subjects at higher risk for developing cognitive
      impairments.

PMID- 9004339
TI  - The effects of age, gender, and season on serotonergic function in healthy
      subjects.
AB  - 1. Several factors, including age, gender, and season of the year, have been
      reported to affect physiologic indices of central serotonergic function, although
      some of these findings have not been consistent across groups of subjects and
      types of serotonergic measures. 2. The authors investigated the role that each of
      these variables might play in the neuroendocrine response to acute intravenous
      challenge with the serotonin reuptake inhibitor clomipramine (CMI) in healthy
      volunteers. 3. Thirty seven healthy subjects (17 women and 20 men), with an age
      range of 19 to 50 years, received 12.5 mg of CMI intravenously under standardized
      conditions. 4. The maximum change from baseline in plasma prolactin
      concentrations ("delta-max") was significantly related to age, after controlling
      for gender and season. 5. In contrast, neither gender nor season was
      significantly related to prolactin delta-max, after controlling for the other two
      variables. 6. Although the age range and sample size are relatively limited, the
      results from this study suggest that age, but not gender or season, may influence
      serotonergic function, as measured by the prolactin response to CMI challenge.

PMID- 9004340
TI  - 20-year chronobiologic study of a middle-aged cyclothymic male subject.
AB  - 1. Cyclothymia is characterized by pronounced but not debilitating shifts of
      moods often lasting approximately two to nine weeks. 2. It can be classified as a
      psychopathologic mood disorder on a continuum to Bipolar II, or as a
      chronobiologic rhythm similar to the circadian except on an infradian time scale.
      3. A male subject diagnosed cyclothymic agreed to daily chart moods and emotions,
      record dreams and monitor physical states. He kept track of hypomania-depression,
      high-low energy, high-low tension, dream affect and sleep parameters. 4. In the
      1,006 affective cycles recorded between 1977 and 1996, four affective phases
      appeared sequentially: being comparable to early hypomania (I, PA), late
      hypomania (II, PD), early depression (III, ND) and late depression (IV, NA). 5.
      During the experiment lasting 20 years, the frequency of the four-phase affective
      cycle increased intermittently from 30.3 days (1977) to 28.0 days (1980), 24.7
      days (1983), 19.0 days (1986), 17.8 days (1989), 12.1 days (1992), and 1.3 days
      (1995). 6. These findings of a four-phase variable infradian rhythm may have
      utility in determining fine structure and time course of rhythms in cyclothymics,
      both medicated and non-medicated, studied outside the clinical laboratory.

PMID- 9004341
TI  - Clozapine eligibility: the effect of stringent criteria on ethnic, gender and age
      subgroups of schizophrenic patients.
AB  - 1. The purpose of this retrospective chart review study was to determine whether
      broad and stringent criteria differentially impact clozapine eligibility in
      ethnic, gender, and age subgroups of schizophrenic patients. 2. 505 patients
      charts were selected from a random cluster sample of mental health patients known
      to the city and county of San Francisco. Information related to clozapine
      eligibility was abstracted by trained non-clinical personnel. The impact of
      subgroup membership on eligibility was examined using logistic regression
      procedures. 3. Even under the broadest interpretation of FDA requirements for
      clozapine use, Asian patients were less likely to be eligible, since fewer Asian
      patients met clozapine treatment requirements. Under more stringent eligibility
      criteria, older patients were more likely to be excluded from eligibility when TD
      does not automatically satisfy treatment criteria, and younger patients were more
      likely to lose eligibility if the number of required adequate medication trials
      increases to three. 4. Broad eligibility criteria tend to differentially exclude
      Asian patients while more stringent criteria differentially exclude younger and
      older patients.

PMID- 9004342
TI  - Differential effects of noradrenergic drugs on anxiety and arousal in healthy
      volunteers with high and low anxiety.
AB  - 1. The appearance of frontal midline theta activity (Fm theta), the distinct EEG
      theta rhythm in the frontal midline area during performance of a mental task,
      indicates relief from anxiety in humans. 2. The authors investigated the effects
      of clonidine and yohimbine on anxiety and arousal in 24 male university students
      with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta.
      Subjects received placebo, 0.15 mg clonidine and 15 mg yohimbine in a double
      blind crossover design. 3. Blood samples were obtained, state-trait anxiety
      inventory (STAI) scores were determined, and EEGs were recorded before and during
      the performance of an arithmetic addition task. The test was repeated twice:
      before and 1 hr after drug administration. 4. Clonidine reduced the 3-methoxy-4
      hydroxyphenylglycol (MHPG) concentration in both groups; yohimbine caused an
      increase in both groups. In the Fm theta group, clonidine reduced the appearance
      time of Fm theta and the number of task performance but did not alter the state
      anxiety scores; yohimbine had no effects on Fm theta or the state anxiety but
      increased the task performance. In the non-Fm theta group, clonidine increased
      the Fm theta amount and reduced the state anxiety score but did not affect task
      performance, while yohimbine reduced Fm theta but increased the state anxiety,
      the task performance and the number of errors. 5. These results suggest that
      changes in noradrenaline (NA) activity affect both anxiety and arousal levels in
      high-anxiety humans, but predominantly affect only the arousal level in low
      anxiety humans.

PMID- 9004343
TI  - Plasma prolactin concentration and psychopathology of schizophrenia.
AB  - 1. The correlation between plasma prolactin concentration and psychopathology, as
      assessed by the BPRS, was studied in 56 unmedicated schizophrenic patients (28
      males, 28 females). 2. There was no significant correlation between plasma
      prolactin concentration and total BPRS score or each item score. 3. No
      significant correlation was found when the BPRS items were classified into five
      clusters, i.e., positive, excitement, cognitive, negative, and anxiety-depression
      symptoms. 4. When males and females were analyzed separately, no significant
      correlation was found except a weak negative correlation (rs = -0.388, p < 0.05)
      for hostility score in females. 5. The present study suggests that plasma
      prolactin concentration does not reflect psychopathology of schizophrenia.

PMID- 9004344
TI  - Effects of methyl beta-carboline-3-carboxylate on memory impairments induced by
      chronic alcohol consumption in mice.
AB  - 1. The effects of systemic administration of beta CCMon the memory impairments
      induced by chronic alcohol consumption in a delayed alternation task were
      studied. 2. For this purpose, Balb/c mice were submitted to chronic alcohol
      treatment during 12 months and were subsequently withdrawn from the alcoholic
      diet at least four weeks before behavioral testing began. 3. Results showed that
      alcohol-treated animals exhibited a delayed alternation deficit that was totally
      reversed by the administration of beta CCM administered before the retention
      trial only. 4. These findings show that the memory deficits observed in alcohol
      treated animals are due to an impairment of the retrieval phase of memory
      processes, and that retrieval memory processes are sensitive to benzodiazepine
      receptor ligands.

PMID- 9004346
TI  - The distribution of noradrenaline, serotonin and gamma-aminobutyric acid in the
      monkey nucleus accumbens.
AB  - 1. The recent histochemical studies have shown that the primate nucleus accumbens
      (NAC) can be subdivided into at least three subdivisions, the medial, ventral and
      dorsolateral subdivisions. 2. The medical subdivision possesses dense peptide-
      and dopamine-immunoreactive (IR) fibers. 3. In order to further investigate the
      neurochemical characteristics of the primate NAC, the distribution of structures
      that contain noradrenaline (NA), serotonin (5-HT) and gamma-aminobutyric acid
      (GABA) were examined in the macaque monkey by using transmitter
      immunohistochemical methods. 4. Many NA-IR fibers were observed in the dorsal
      part of the NAC, corresponding to the medial subdivision. Fine varicose 5-HT-IR
      fibers were evenly distributed in the NAC. GABA-IR cell bodies and puncta were
      observed throughout the NAC as well as in the caudate nucleus and putamen. 5. The
      monkey rostral NAC displays a highly homogeneous distribution of all
      neuropeptides and neurotransmitters studied so far and we propose that this
      region be termed the rostral subdivision of the NAC.

PMID- 9004345
TI  - A schematic representation of the psychopharmacological profile of
      antidepressants.
AB  - 1. Using simple animal tests, "behavioural" and "biochemical" aspects of
      depression, anxiolysis, disinhibition, psychostimulation and sedation were
      investigated in mice using a variety of antidepressant drugs. 2. Dothiepin and
      mianserin (16 and 32 mg/kg), fluoxetine (32 and 64 mg/kg), maprotiline and
      imipramine (16, 32 and 64 mg/kg) and viloxazine (16 mg/kg) significantly
      potentiated mortality following acute administration with yohimbine. 3. Dothiepin
      and imipramine (32 mg/kg), fluoxetine (16 and 32 mg/kg), viloxazine (8 and 16
      mg/kg), maprotiline (32 mg/kg) and mianserin (32 mg/kg) reduced immobility time
      in the forced swimming test. 4. In the black and white box, dothiepin (32 mg/kg)
      significantly increased the time spent in the bright compartment: Fluoxetine (8
      and 16 mg/kg) significantly increased the number of crossings between
      compartments, an effect indicative of desinhibition. 5. It can be concluded that
      dothiepin possesses both antidepressant and anxiolytic properties in these animal
      models. The present procedure is useful not only for the screening of compounds
      that may possess antidepressant properties, but is also of value in determining
      other properties that may contribute to the overall clinical efficacy of the
      drugs.

PMID- 9004347
TI  - A novel benzodiazepine inverse agonist, S-8510, as a cognitive enhancer.
AB  - 1. Pharmacological actions of a novel benzodiazepine receptor ligand, S-8510 (2
      (3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano+ ++[4,3-b] pyridine
      monophosphate monohydrate), were examined in in vitro and in vivo studies. 2. S
      8510 was characterized as a partial inverse agonist with a modest GABA ratio and
      low efficacy. 3. S-8510 ameliorated memory impairment induced by cholinergic
      deficit in the water maze paradigm of Wistar rats. 4. S-8510 augmented LTP of the
      Schaffer collateral/commissural fiber-CA1 synapses in the hippocampal slice
      preparations of SD rat. 5. S-8510 increased the extracellular levels of
      acetylcholine and noradrenaline in the hippocampus of Wistar rat. 6. S-8510
      selectively potentiated pentylenetetrazol-induced convulsion without affecting
      minimal electroconvulsive shock- or strychnine-induced convulsion in ddY mice. 7.
      S-8510 failed to induce any sign of anxiety in the Wistar rat pro-conflict test.
      8. S-8510 showed antidepressant-like pharmacological actions in ddY mice. 9.
      These results suggest that S-8510 can be used as a therapeutic drug for senile
      dementia, including Alzheimer's disease with little risk for inducing anxiety or
      convulsion.

PMID- 9004348
TI  - Raphe-septal neurons changes in sensitivity to desipramine following an early
      septal lesion in the rat.
AB  - 1. The electrophysiological responsivity to desipramine (DMI) applied by systemic
      or local route was tested in Wistar female rats submitted to a wide lesion in the
      lateral septal area on the 8th day after birth. 2. One year after a septal
      lesion, the dorsal raphe nucleus (DRN) stimulation produced an initial brief
      response in lateral septal and CA1/CA3 neurons. In the control and sham-lesion
      groups, most recordings showed only this initial brief response (non-late
      responding neurons); however, in the lesion group most of the recorded neurons
      showed an afterdischarge. 3. DMI (2.14 mg/kg, 21 days, i.p.) increased the firing
      rate in septal and CA1/CA3 non-late responding neurons. In the equivalent septal
      neurons from lesion group, DMI produced the inverse effect, i.e., a decreased
      firing rate. 4. In septal non-late responding neurons, DMI (2 mM; 10-15 nAmps,
      0.5 sec) applied by microiontophoresis increased the firing rate only after long
      term systemic DMI impregnation. The response to locally applied DMI did not occur
      in the lesion group even after long-term DMI treatment. 5. In conclusion, an
      early lateral septal lesion canceled the response of intermediate-dorsal septal
      neurons to DMI applied by systemic and local routes.

PMID- 9004349
TI  - Serotonin in the regulation of brain microcirculation.
AB  - Manipulation of brainstem serotonin (5-HT) raphe neurons induces significant
      alterations in local cerebral metabolism and perfusion. The vascular consequences
      of intracerebrally released 5-HT point to a major vasoconstrictor role, resulting
      in cerebral blood flow (CBF) decreases in several brain regions such as the
      neocortex. However, vasodilatations, as well as changes in blood-brain barrier
      (BBB) permeability, which are blocked by 5-HT receptor antagonists also can be
      observed. A lack of relationship between the changes in flow and metabolism
      indicates uncoupling between the two variables and is suggestive of a direct
      neurogenic control by brain intrinsic 5-HT neurons on the microvascular bed. In
      line with these functional data are the close associations that exist between 5
      HT neurons and the microarterioles, capillaries and perivascular astrocytes of
      various regions but more intimately and/or more frequently so in those where CBF
      is altered significantly following manipulation of 5-HT neurons. The ability of
      the microvascular bed to respond directly to intracerebrally released 5-HT is
      underscored by the expression of distinct 5-HT receptors in the various cellular
      compartments of the microvascular bed. Thus, it appears that while some 5-HT
      mediated microvascular functions involve directly the blood vessel wall, others
      would be relayed through the perivascular astrocyte. The strategic localization
      of perivascular astrocytes and the different 5-HT receptors that they harbor
      strongly emphasize their putative pivotal role in transmitting information
      between 5-HT neurons and microvessels. It is concluded that the cerebral
      circulation has full capacity to adequately and locally adapt brain perfusion to
      changes in central 5-HT neurotransmission either directly or indirectly via the
      neuronal-astrocytic-vascular tripartite functional unit. Dysfunctions in these
      neurovascular interactions might result in perfusion deficits and might be
      involved in specific pathological conditions.

PMID- 9004350
TI  - Neuronal-specific gene expression--the interaction of both positive and negative
      transcriptional regulators.
AB  - Gene expression patterns in neurons are complex and are modulated in response to
      multiple extracellular stimuli. In addition, during development and as neurons
      differentiate into distinct neuronal phenotypes, there is a co-ordinated
      activation and repression of a variety of genes. It is becoming increasingly
      evident that negative regulatory elements are present in neuronal-specific
      promoters. These elements have been shown, in part, to restrict promoter activity
      to the correct physiological cell type, both in transient transfection and in
      transgenic mouse models. Repression can be effected by different mechanisms
      depending on location within the promoter of silencer complexes and their
      relationship to other bound transcription factors. This review will discuss the
      molecular mechanisms regulating promoter function, in particular: (1) the
      combinatorial interaction between transcription factors which generate regulated
      promoter function; and (2) the restriction of promoter function to the correct
      cell type by bound repressor molecules. Determination of the mechanism of
      regulated gene expression will allow advances in gene therapy and definition of
      novel targets for pharmaceutical intervention. At the more basic level,
      functional dissection of the promoters of specific neuronal expressed genes will
      provide information of importance in two key areas of neurobiology: (1) the
      mechanism by which extracellular factors, such as neurotrophins and cytokines,
      regulate gene expression; (2) the events which lead to the tissue-specific
      expression of genes in subpopulations of neurons, both in the adult and during
      development.

PMID- 9004351
TI  - The basal ganglia: focused selection and inhibition of competing motor programs.
AB  - The basal ganglia comprise several nuclei in the forebrain, diencephalon, and
      midbrain thought to play a significant role in the control of posture and
      movement. It is well recognized that people with degenerative diseases of the
      basal ganglia suffer from rigidly held abnormal body postures, slowing of
      movement, involuntary movements, or a combination of these a abnormalities.
      However, it has not been agreed just what the basal ganglia contribute to normal
      movement. Recent advances in knowledge of the basal ganglia circuitry, activity
      of basal ganglia neurons during movement, and the effect of basal ganglia lesions
      have led to a new hypothesis of basal ganglia function. The hypothesis states
      that the basal ganglia do not generate movements. Instead, when voluntary
      movement is generated by cerebral cortical and cerebellar mechanisms, the basal
      ganglia act broadly to inhibit competing motor mechanisms that would otherwise
      interfere with the desired movement. Simultaneously, inhibition is removed
      focally from the desired motor mechanisms to allow that movement to proceed.
      Inability to inhibit competing motor programs results in slow movements, abnormal
      postures and involuntary muscle activity.

PMID- 9004353
TI  - TLD extrapolation for skin dose determination in vivo.
AB  - Prediction of skin reactions requires knowledge of the dose at various depths in
      the human skin. Using thermoluminescence dosimeters of three different
      thicknesses, the dose can be extrapolated to the surface and interpolated between
      the different depths. A TLD holder was designed for these TLD extrapolation
      measurements on patients during treatment which allowed measurements of entrance
      and exit skin dose with a day to day variability of +/-7% (S.D. of mean reading).
      In a pilot study on 18 patients undergoing breast irradiation, it was found that
      the angle of incidence of the radiation beam is the most significant factor
      influencing skin entrance dose. In most of these measurements the beam exit dose
      contributed 50% more to the surface dose than the entrance dose.

PMID- 9004352
TI  - Mucosal regeneration during radiotherapy. Trans Tasman Radiation Oncology Group
      (TROG).
AB  - BACKGROUND AND PURPOSE: Regeneration of the aerodigestive mucosa is known to
      occur during conventionally fractionated radiotherapy. The circumstances
      surrounding its time of onset and magnitude are not well understood, however.
      MATERIAL AND METHODS: Mucosal reactions were observed in 100 patients undergoing
      conventionally fractionated treatment at 2 Gy/day over 7 weeks and 88 receiving
      accelerated treatment at 1.8 Gy twice daily over 3 1/2 weeks on the Trans Tasman
      Radiation Oncology Group head and neck cancer trials. Similar observations in 61
      patients treated palliatively at dose rates between 0.8 and 240 Gy/h using ten
      3.0-4.2 Gy fractions over 2 weeks are compared. RESULTS: Several findings emerged
      from these studies: 1. Reactions evolved more quickly at oropharyngeal sites than
      in the hypopharynx. 2. Reactions at both sites evolved more rapidly at greater
      rates of dose accumulation. 3. The timing of reactions suggested the presence of
      a strong regenerative mucosal response that started before the manifestation of
      "patchy' (grade II) mucosal reactions. 4. The regenerative response was strong
      enough to "make good' damage accumulated at a rate of 2 Gy/day in over a third of
      cases. 5. The linear quadratic model without time correction failed to provide an
      adequate prediction of the frequency or intensity of mucosal reactions produced
      by any of the regimes. A simple model of the regenerative response is presented.
      CONCLUSIONS: This study suggests that the timing and magnitude of the
      regenerative response vary between sites and individuals but are linked to the
      amount of epithelial cellular depletion occurring during treatment.

PMID- 9004355
TI  - Pulsed dose rate (PDR) brachytherapy of anal carcinoma.
AB  - BACKGROUND AND PURPOSE: With radiotherapy of anal carcinomas, sphincter
      preservation can be obtained at survival rates similar to those obtained with
      radical surgery. By combining external beam irradiation with interstitial
      irradiation, superiority over standard external irradiation has been obtained.
      With the introduction of pulsed dose rate equipment, where a single high activity
      source moves through catheters, a more individualized dose distribution and a
      further elimination of radiation exposure to the staff can be achieved. MATERIALS
      AND METHODS: Between June 1993 and November 1994, 17 patients with anal carcinoma
      (T1:4, T2:4, T3:6, T4:3) have been treated at the Finsen Center. The treatment
      consisted of three-field external irradiation 46 Gy/23 fractions with five
      fractions a week to the anal canal and regional pelvic lymph nodes. Seven to 33
      days after completion of external irradiation, the tumorspace was given 25.2 Gy
      PDR brachytherapy with 42 pulses of 0.6 Gy, one pulse every hour. RESULTS: One
      isolated local recurrence has been noted 13 weeks after implantation. One
      additional local recurrence was seen in a patient with concomitant hepatic and
      inguinal recurrence. In three patients inguinal recurrence had occurred, two of
      these patients were irradiated without any further evidence of disease, and one
      patient with a primary advanced tumour, had local failure. So far necrosis has
      been observed in 13 patients within 1-49 weeks (median 16 weeks) after
      implantation. Eight of these patients required colostomy. No relation was
      observed between the number of implanted needles and the occurrence of necrosis.
      CONCLUSIONS: The results indicate that the treatment is highly effective, but
      with substantial toxicity.

PMID- 9004354
TI  - Pilot study of intraoperative high dose rate brachytherapy for head and neck
      cancer.
AB  - PURPOSE: To develop a new technique, intraoperative high dose rate brachytherapy
      (IOHDR), to deliver localized radiation therapy intraoperatively to head and neck
      tumors at sites inaccessible to intraoperative electron beam radiotherapy
      (IOEBRT) in the skull base region. METHODS: After maximal surgical resection,
      afterloading catheters spaced 1 cm apart embedded in custom surface applicators
      made of foam or silicone were placed on resected tumor beds. IOHDR was delivered
      in a shielded operating room using preplanned dosimetry with a nominal 10 Ci
      iridium-192 source in an HDR micro-Selectron afterloader. Twenty-nine patients
      (20 males, 9 females) ranging in age from 9 to 80 years (median = 61) were
      irradiated intraoperatively for advanced head and neck tumors at sites
      inaccessible to IOEBRT. Six patients who had previously received external beam
      radiation (EBRT) ranging from 50 to 75 Gy, were given 15 Gy of IOHDR only. Twenty
      three patients who had no prior radiation received 7.5 to 12.5 Gy IOHDR, and 45
      to 50 Gy EBRT was planned post-operatively; however, six of these patients did
      not complete the planned EBRT. Doses to normal tissues were reduced whenever
      possible by shielding with lead or by displacement with gauze or retractors.
      Treatment time ranged from 3.8 to 23 min (median = 6.5 min). Five patients
      received concurrent cis-platinum based chemotherapy. RESULTS: Twenty-nine
      patients treated to 30 sites had local tumor control of 67% and crade survival of
      72%, with the follow-up ranging from 3 to 33 months (median = 21 months). In the
      group of 17 previously unirradiated patients who had completed full treatment
      (IOHDR and EBRT) to 18 sites, the local tumor control was 89%, and all of these
      patients survived. Tumor control in the six previously unirradiated patients who
      did not complete EBRT was 50% with a crude survival of 50%. In the group of six
      previously irradiated patients treated by IOHDR only, the local tumor control was
      17% with a crude survival of 17%. No intraoperative complications were noted. The
      delayed morbidity included cerebrospinal fluid (CSF) leak with bone exposure (1),
      chronic subdural hematoma (1), septicemia (1), otitis media (1), and severe
      xerostomia (1). We cannot comment on long-term morbidity due to the relatively
      short follow-up period of 21 months. CONCLUSIONS: It is feasible to deliver
      IOHDR, with acceptable toxicity, to skull base tumors at sites inaccessible to
      IOEBRT. The use of IOHDR as a pre-radiotherapy boost produced excellent local
      control and survival in the selected group of patients who had no previous
      radiation therapy. The use of exclusive IOHDR in the previously irradiated group
      resulted in poor outcome, possibly due to the limitations on re-irradiation doses
      and/or volumes determined by normal tissue tolerance or because these patients
      have inherently radioresistant tumors. Higher IOHDR doses, additional EBRT,
      and/or chemotherapy should be considered for this group. The use of IOHDR as a
      pre-EBRT boost to maximize local control has a promising future in the treatment
      of carefully selected patients with advanced skull base tumor.

PMID- 9004356
TI  - Radiotherapy for primary squamous cell carcinoma of the trachea.
AB  - Twenty-two patients with tracheal squamous cell carcinoma were treated by
      radiotherapy alone. Nine patients were treated with 60 Gy between 1982 and 1987
      and 13 with 70 Gy between 1988 and 1993 using conventional fractionation. The
      median survival was 24 months and the 5-year survival rate was 27%. Patients
      receiving 70 Gy had a slightly better prognosis than those receiving 60 Gy, but
      the difference was not significant. Patients with mediastinal lymph node
      involvement had a significantly worse prognosis. Delayed tracheal toxicity tended
      to be higher in the 70 Gy group.

PMID- 9004357
TI  - Serial cytological assay of micronucleus induction: a new tool to predict human
      cancer radiosensitivity.
AB  - BACKGROUND AND PURPOSE: The micronucleus test, generally done in cultured tumour
      cells irradiated in vitro, has not gained wide acceptance in predicting human
      cancer radiosensitivity. The purpose of this study was to see if micronucleus
      assay by serial scrape smear cytology can predict oral cancer radiosensitivity.
      MATERIALS AND METHODS: Forty nine oral cancer patients given radiotherapy (60
      Gy/25 fractions/5 weeks) form the study population. Serial scrape smears were
      taken from their tumours before treatment and after delivery of 2, 5, 8 and 12
      fractions, stained by Giemsa and the number of micronucleated cells (MNC) noted.
      The patients were grouped to those who developed tumour recurrence ('Resistant')
      and those who did not ('Sensitive'), and the pattern of micronucleus induction
      compared. RESULTS: Both groups of tumours had MNC even before treatment, with
      statistically significant dose-related increase with radiotherapy. The sensitive
      group had a higher mean increase in MNC count than the resistant group (6.1 times
      and 3.6 times the pre-treatment value, respectively) and better correlation with
      dose (r = 0.54 vs. 0.43). The increase in MNC count occurred earlier in the
      resistant group than in the sensitive, the TMNC (time for the pre-treatment value
      to double) being 3.3 days and 7.6 days, respectively. Also, the resistant group
      showed a plateauing of the MNC count which the sensitive group lacked.
      CONCLUSIONS: The higher MNC induction in the sensitive tumours suggests the
      usefulness of the assay as a test of radiosensitivity. The differing patterns of
      MNC increase suggest that differences in proliferation rate is an important cause
      of tumour failure. Serial cytological assay of micronucleus induction can
      identify both radiosensitivity and proliferation characteristics of tumours, and
      thus may turn out to be a useful test of radiocurability.

PMID- 9004358
TI  - Efficacy of agents counteracting hypoxia in fractionated radiation regimes.
AB  - BACKGROUND AND PURPOSE: Solid tumours contain hypoxic cells which are resistant
      to radiotherapy. This study compares the efficacy of several strategies to
      counteract diffusion-limited hypoxia, or intermittent hypoxia in a fractionated
      regimen of 1 to 6 x 2 Gy. MATERIALS AND METHODS: Nicotinamide (250 mg/kg),
      perflubron emulsion (Oxygent) (4 ml/kg), tirapazamine (SR4233) (0.10 mmol/kg) and
      carbogen breathing, administered alone or in combination, were investigated on
      two tumour cell lines: EMT6 (a rodent mammary carcinoma) and HRT18 (a human
      rectal adenocarcinoma) using a clonogenic assay. The radiosensitizing effect of
      the agents was assessed after 1 and 6 x 2 Gy for drugs used alone, and 1, 2, 4, 6
      x 2 Gy for drugs used in combination. RESULTS: At the end of the fractionated
      radiation regimen, the combination of nicotinamide + carbogen induced the
      greatest radiosensitization for EMT6 tumours, while greatest radiosensitization
      of HRT18 was obtained with nicotinamide + carbogen + tirapazamine. CONCLUSION:
      The efficacy of the strategies for overcoming hypoxia using a fractionated
      regimen depends on the tumour cell line. These differences could be linked to
      differences in the initial percentages of acute and chronic hypoxic cells, and to
      changes in the two types of hypoxia during treatment.

PMID- 9004360
TI  - Enhancement of radiation effect by Ginkgo biloba extract in C3H mouse
      fibrosarcoma.
AB  - BACKGROUND AND PURPOSE: Ginkgo biloba leaf extract (GBE) is known to increase
      peripheral blood circulation. The hypothesis that GBE may be able to enhance
      radiosensitivity of tumor by improving tumor blood flow and thus decreasing
      hypoxic fraction was tested. MATERIALS AND METHODS: Fibrosarcoma (FSaII) growing
      in C3H mouse leg muscle was used as a tumor model. GBE was given i.p. 1 h before
      irradiation with or without priming dose given 1 day earlier. Effect on tumor and
      normal tissue radiation reaction was investigated. RESULTS: Tumor growth delay by
      radiation was more elongated after two doses (1-day interval) of GBE than after a
      single dose. Radiation dose for 3-day tumor growth delay was decreased from 12.45
      (10.97-13.93) Gy to 6.06 (3.89-8.22) Gy by two doses of GBE [enhancement ratio =
      2.06 (1.32-2.79)]. Hypoxic cell fraction was 10.6% (6.3-18.2%) for control, 7.2%
      (3.8-14.0%) after a single dose (P = 0.18) and 2.7% (1.5-5.0%) after two doses (P
      < 0.001). Radiation effect on normal tissue, estimated by acute skin reaction and
      jejunal crypt assay, was not affected by GBE. CONCLUSION: Ginkgo biloba extract
      enhances radiation effect on tumor without increasing acute normal tissue
      radiation damage in this model system probably by increasing tumor blood flow and
      further investigation for this possible radiosensitizer is needed.

PMID- 9004359
TI  - Proposal for translational analysis and development of clinical radiolabeled
      immunoglobulin therapy.
AB  - BACKGROUND AND PURPOSE: Radiolabeled immunoglobulin therapy (RIT) can be a
      selective, effective, low-toxicity outpatient cancer therapy. A consensus on the
      best approach for the preclinical and clinical development of RIT reagents needs
      to be developed. We report the M.D. Anderson Cancer Center prior experience in
      translating RIT from laboratory to clinic for the treatment of Hodgkin's disease
      and propose a flow diagram for the development of RIT for other malignancies.
      MATERIAL AND METHODS: Three different animal models are described: nude mice
      bearing human tumor xenografts, normal beagle dogs, and normal rhesus monkeys. We
      produced and purified antibodies and prepared chelate-immunoconjugates reactive
      with six different human tumor-associated antigens. The Igs used were derived
      from rabbits, mice, and humans (human-derived RIT reagents being less immunogenic
      in human patients). Eighty patients with refractory Hodgkin's disease were
      treated with radiolabeled antiferritin. RESULTS: We recommend a two-injection
      scheme using, (1) an indium-111-labeled radioimmunoconjugate for diagnosis,
      pharmacokinetic studies, and dosimetry, and (2) a yttrium-90-labeled
      radioimmunoconjugate for therapy. The animal models provide useful data on tumor
      targeting, radiotoxicology, and undesirable biodistributions. A 70% response rate
      is obtained in patients with advanced recurrent Hodgkin's disease. More extensive
      preclinical testing allows for safer and more effective clinical RIT studies.
      CONCLUSIONS: We recommend, (1) preclinical optimization of chelation chemistry,
      Ig size, Ig origin, route of administration, and fractionation, (2) new clinical
      Phase I-III studies more appropriate for RIT development than the classical Phase
      I-III studies used for the development of chemotherapeutic agents, and (3) more
      extensive preclinical testing of RIT reagents.

PMID- 9004362
TI  - Entrance and exit dose measurements with semiconductors and thermoluminescent
      dosemeters: a comparison of methods and in vivo results.
AB  - BACKGROUND AND PURPOSE: In order to compare diodes and TLD for in vivo dosimetry,
      systematic measurements of entrance and exit doses were performed with
      semiconductor detectors and thermoluminescent dosemeters for brain and head and
      neck patients treated isocentrically with external photon beam therapy. MATERIAL
      AND METHODS: Scanditronix EDP-20 diodes and 7LiF thermoluminescent chips,
      irradiated in a 8 MV linac, were studied with similar build-up cap geometries and
      materials in order to assure an equivalent electronic equilibrium. Identical
      calibration methodology was applied to both detectors for the dose determination
      in clinical conditions. RESULTS: For the entrance dose evaluation over 249 field
      measurements, the ratio of the measured dose to the expected dose, calculated
      from tabulated tissue maximum ratios, was equal to 1.010 +/- 0.028 (1 s.d.) from
      diodes and 1.013 +/- 0.041 from thermoluminescent crystals. For the exit dose
      measurements, these ratios were equal to 0.998 +/- 0.049 and 1.016 +/- 0.070 for
      diodes and TLDs, respectively, after application of a simple inhomogeneity
      correction to the calculation of the expected exit dose. CONCLUSIONS:
      Thermoluminescence and semiconductors led to identical results for entrance and
      exit dose evaluation but TLDs were characterised by a lower reproducibility
      inherent to the TL process itself and to the acquisition and annihilation
      procedures.

PMID- 9004361
TI  - Proton dosimetry intercomparison.
AB  - BACKGROUND AND PURPOSE: Methods for determining absorbed dose in clinical proton
      beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both
      groups recommend the use of air-filled ionization chambers calibrated in terms of
      exposure or air kerma in a 60Co beam when a calorimeter or Faraday cup dosimeter
      is not available. The set of input data used in the AAPM and the ECHED protocols,
      especially proton stopping powers and w-value is different. In order to verify
      inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED
      recommend periodic dosimetry intercomparisons. In this paper we report the
      results of an international proton dosimetry intercomparison which was held at
      Loma Linda University Medical Center. The goal of the intercomparison was two
      fold: first, to estimate the consistency of absorbed dose delivered to patients
      among the participating facilities, and second, to evaluate the differences in
      absorbed dose determination due to differences in 60Co-based ionization chamber
      calibration protocols. MATERIALS AND METHODS: Thirteen institutions participated
      in an international proton dosimetry intercomparison. The measurements were
      performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam
      (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal
      accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm
      at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator
      energy of 100 MeV). RESULTS: The results of the intercomparison have shown that
      using ionization chambers with 60Co calibration factors traceable to standard
      laboratories, and institution-specific conversion factors and dose protocols, the
      absorbed dose specified to the patient would fall within 3% of the mean value. A
      single measurement using an ionization chamber with a proton chamber factor
      determined with a Faraday cup calibration differed from the mean by 8%.
      CONCLUSION: The adoption of a single ionization chamber dosimetry protocol and
      uniform conversion factors will establish agreement on proton absorbed dose to
      approximately 1.5%, consistent with that which has been observed in high-energy
      photon and electron dosimetry.

PMID- 9004363
TI  - Feasibility study of multileaf collimated electrons with a scattering foil based
      accelerator.
AB  - BACKGROUND AND PURPOSE: There is an ever evolving process to improve the
      technical aspects of electron beam delivery. Both the foil/applicator and
      scanning electron beam systems have gone through recent upheavals. Concomitantly,
      multileaf collimators are now a staple method for collimating photons. We
      undertook a study of multileaf collimated electron beam (MLCEB) using a dual
      scattering foil system. MATERIALS AND METHODS: We compared MLCEB with applicator
      collimated electron beams (AEB) by examining the dosimetric aspects of the two
      systems using 70 and 80 cm SSDs for the MLCEB, the minimum practical SSDs
      achievable. Percent depth dose, isodose profiles, output factors, leakage,
      surface dose, bremstrahlung, effective SSDs, etc. were measured using film and/or
      ion chamber. Clinical fields, such as posterior neck node (PNN), were compared.
      We also investigated the use of MLCEB for arc therapy using segments. RESULTS: In
      all cases, the MLCEB performed inferior, as judged by isodoses, uniformity index
      (UI) and penumbra analysis. The 80 cm SSD (minimum for PNN), low energy, small
      fields, was the worst case. For a 6 MeV beam, the UI/penumbra was 0.823/10 mm for
      the AEB, and 0.561/29 mm for the MLCEB at 80 cm SSD. The PNN multileaf fields
      exhibited narrow 90% and 80% isodose lines, and wide 20% and 10% lines.
      CONCLUSIONS: We conclude that multileaf for PNN fields could not be matched to
      adjacent off-cord photon fields. The "stair-stepping' effect associated with MLC
      photons was absent for electrons.

PMID- 9004364
TI  - Factors affecting the most recent fertility rates in urban-rural Bangladesh.
AB  - This paper reports on a study which has been undertaken using data from the 1989
      Bangladesh Fertility Survey (BFS) to determine the significance of influences on
      the probability of birth in the year preceding the survey. In the survey a total
      of 11905 ever-married women of reproductive age were asked a battery of questions
      relating to fertility aspects of women. Variables selected in this study were
      grouped into demographic, socio-economic, cultural and decision-making variables.
      Findings from the study indicate that the mother's age, whether contraception has
      ever been used, the death of a child at any time, whether the woman has ever
      worked, religion, region of residence, and female independence are the important
      covariates for explaining recent fertility in Bangladesh. Models are developed
      for the probabilities of a woman giving birth in urban and rural areas, dependent
      on her demographic and socio-economic conditions. Also developed are models for
      contraceptive use in urban-rural Bangladesh. This modelling contributes to a
      better understanding of fertility changes in Bangladesh and the differentials
      between urban and rural fertility. It is indicated that a continued fertility
      decline is likely.

PMID- 9004365
TI  - The children's sentinels: mothers and their relationships with health
      professionals in the context of Japanese health care.
AB  - The context of the Japanese health care setting shaped Japanese women's roles as
      the major and solo caretakers of their ill children, which caused them to be
      removed from the family unit during the children's illness. The mothers became
      sentinels and tried to protect their children from unnecessary physical and
      psychological distress and agony in the hospital context. Some of them comforted
      their children in the home-care context once their children reached the point
      where no other treatment could help. At the same time, they tried to establish
      effective relationships with health professionals, especially physicians. One
      third of the mothers gave the initiative to the physician, but almost half of the
      mothers shared the initiative to some degree with physicians on an equal or
      dominant-subordinate basis. Whether the mothers trusted the physicians did not
      relate to whether they shared the initiative or not, but was a primary factor in
      deciding whether to change hospitals. The mothers became monitors and advocates
      of their children during treatment, at first choosing to adapt to their
      subordinate position in the hospital, but becoming more assertive when they felt
      their children may be seriously harmed.

PMID- 9004366
TI  - The ellipsis of prognosis in modern medical thought.
AB  - Contemporary textbooks of internal medicine give scant attention to the prognosis
      of diseases. Has this always been the case? If not, when and why did prognosis
      come to be de-emphasized? Using a highly regarded, standard medical textbook
      initially authored by William Osler, The Principles and Practice of Medicine, I
      performed qualitative and quantitative content analysis of entries regarding
      lobar pneumonia in selected editions published between 1892 and 1988, with
      special attention to the period between 1892 and 1947. I chose lobar pneumonia
      because it was a leading cause of death throughout this period and because it is
      recognizable across time, thus making it possible to follow the evolution in
      clinical thinking about prognosis while holding constant the diagnosis. I argue
      that two powerful forces converged to lead to the ellipsis of prognosis: (1) the
      emergence of effective therapy, and (2) a fundamental change in the cognitive
      basis of medicine. With respect to the former, I show that there is a
      complementary, inverse relationship between the clinical acts of prognostication
      and therapy; as one increases in salience in the management of a disease, the
      other decreases. With respect to the latter, I argue that the particular clinical
      facts deemed to be important about a patient's case have shifted over time, and I
      explore changes in the clinical and cognitive foundations of physicians'
      estimation of patients' prognoses-in particular, "symptoms" and "complications."
      I conclude that, concurrent with a shift in clinical thought from an individual
      based to a diagnosis-based conceptualization of disease, prognosis came to be
      seen as intrinsic to diagnosis and therapy, and explicit attention to prognosis
      consequently diminished.

PMID- 9004367
TI  - Perceived social support, family environment and psychosocial recovery in bone
      marrow transplant long-term survivors.
AB  - This report examines perceptions of social support and family dynamics in bone
      marrow transplant (BMT) long-term survivors, as part of a larger study examining
      issues of quality of life and psychosocial adjustment in this patient group.
      Ninety one BMT survivors participated in the study. Their responses were compared
      with those of a matched control group of 73 patients receiving maintenance
      chemotherapy (MC). The results indicated that the BMT group received more social
      support than the MC group. Main sources of support were the patients' immediate
      family members. No significant differences in the typology and dynamics of family
      environments were observed between groups. However, the groups were significantly
      different compared with healthy, non-distressed families in cohesion, control and
      conflict. It was of importance to note that a considerable number of BMT subjects
      reported at least one nurse as a person who provides support to them, indicating
      the potential important role of nurses in the psychosocial adjustment of BMT long
      term survivors. Strong family relationships were associated in both the BMT and
      MC groups with significantly better adjustment with respect to their domestic,
      extended family or social environment, and psychological distress. Social support
      and family relationships might be two of the main spheres of life contributing to
      higher levels of quality of life, and their important role as a stressor-filter
      is highlighted.

PMID- 9004368
TI  - Past or present? Childhood living conditions and current socioeconomic status as
      determinants of adult health.
AB  - The aim was to study the associations of childhood living conditions, together
      with past and present socioeconomic status, with adult health among Finnish men
      and women. The data were derived from a nationwide interview Survey on Living
      Conditions collected by Statistics Finland in 1986. The sample represents the non
      institutional Finnish population aged 15 years or older. The number of
      respondents was 12,057 and the response rate 87%. In this study we analysed 30
      year-old and older subjects. Two health indicators were analysed: first, limiting
      long-standing illness; and second, self-assessed health as "below good". Four
      different indicators of childhood living conditions were included: one concerning
      economic problems, and three concerning family related social problems during
      childhood. Additionally, the degree of urbanisation of the childhood living area
      was examined. Past and present socioeconomic status were measured by the status
      of origin, i.e. the respondent's father's and mother's education, and the status
      of destination, i.e. the respondent's own current education. Economic problems
      during childhood were associated with current health. The association of
      childhood social problems with health was somewhat weaker and less consistent
      than that of economic problems. A comparison of the mutual impacts of economic
      and social problems, respectively, shows that economic problems are stronger and
      more independent determinants of adult health than social problems. According to
      multivariate logistic regression analysis, past and, particularly, present
      socioeconomic status are both important determinants of adult health. Current
      socioeconomic status showed strongest associations with adult health, but living
      conditions during upbringing, particularly economic problems and status of
      origin, were also significant predictors.

PMID- 9004369
TI  - Social scientists and the new tuberculosis.
AB  - In much of the world, tuberculosis (TB) remains the leading killer of young
      adults, in spite of the fact that effective chemotherapy has existed for 50
      years. The epidemiology of TB, with its persistence in poor countries and
      resurgence among the poor of many industrialized nations, causes consternation
      among those charged with protecting the public's health. Two factors, ostensibly
      biological in nature, are commonly cited to explain this setback: the advent of
      HIV and the emergence of TB strains resistant to multiple drugs (MDR TB). But the
      strikingly patterned occurrence of MDR TB-in the United States afflicting those
      in homeless shelters and in the inner city, for example-speaks to some of the
      large-scale social forces at work in the new epidemic, which began before the
      advent of HIV. These forces (which include poverty, economic inequality,
      political violence, and racism) are examined through the experience of a young
      Haitian man with MDR TB, a disease never before described in Haiti. Insights from
      this case, and from other research on TB and HIV disease, are considered in the
      light of past anthropological writings on TB. It is argued that, often, social
      scientists mar contributions to an understanding of TB by making "immodest claims
      of causality" regarding its distribution and course. Alternative strategies for
      future sociomedical research on MDR TB are proposed.

PMID- 9004370
TI  - Gender, social pressure, and smoking cessations: the Community Intervention Trial
      for Smoking Cessation (COMMIT) at baseline.
AB  - This study was undertaken to examine gender differences in the perception of
      social constraints against smoking and to explore the role of other
      sociodemographic and smoking factors that influence the perception of social
      pressure. Baseline data from the 20 U.S. sites in the National Cancer Institute's
      Community Intervention Trial for Smoking Cessation (COMMIT) were analyzed. We
      found that women were less likely than men to be heavy smokers and to report that
      smoking had affected their health, but more likely to report behavior indicating
      physiological addiction (timing of first cigarette). At all smoking levels, women
      were about twice as likely as men to report feeling pressure to quit, after
      adjusting for education, income, ethnic group, age, and other factors. The source
      of pressure, however, was different: more women report pressure from their
      children, whereas more men report pressure from friends and coworkers. Women were
      equally likely as men to make quit attempts, after adjusting for other factors,
      but were less likely to remain abstinent for at least 10 days. Women, regardless
      of education, ethnicity, and age, reported a greater tendency to ask permission
      before smoking in non-restricted public places. College-educated men were less
      likely than men without college education to smoke without asking in non
      restricted places, but education did not influence whether women asked
      permission. For both sexes, smoking level and nicotine dependence were
      significant predictors of lighting up without asking in public places, after
      adjustment for other variables. We discuss these findings and their implications
      for the gender gap in smoking cessation and women's conflicting pressures to
      stop/continue smoking. Tobacco control efforts are discussed within the context
      of gender differences in social norms, roles, socialization, and communication
      cultures.

PMID- 9004371
TI  - Using willingness to pay to value alternative models of antenatal care.
AB  - Recent years have seen the development of different models of antenatal care,
      especially for low risk women. More specifically, there has been a move for more
      general practitioner and midwifery involvement in such care. Given the current
      changes that are taking place in the provision of antenatal care, it is becoming
      increasingly important to carry out economic evaluations of alternative models of
      care. This paper applies the economic instrument of willingness to pay to assess
      the benefits of two alternative forms of antenatal care: general
      practitioner/midwife routine led care versus obstetrician led care. The results
      suggest a willingness to pay of pounds 2500 for antenatal care, with no
      significant difference between the types of care provided. It is concluded that
      before firm policy conclusions can be reached, further studies should be
      undertaken to address methodological issues around the willingness to pay
      technique.

PMID- 9004372
TI  - Female and male physicians' attitudes toward prenatal diagnosis: a Pan-Canadian
      survey.
AB  - Despite widespread use over the past 20 years, prenatal diagnosis (PND) remains a
      controversial technique because of the moral and organizational dilemmas that it
      raises in many countries. In order to assess attitudes to PND within the Canadian
      medical profession, a survey was carried out involving over 3000 physicians
      offering PND (general practitioners, obstetricians, pediatricians, and
      radiologists). Several scales were developed to measure (1) physicians'
      willingness to broaden access to PND, (2) acceptability of abortion when a fetal
      anomaly is diagnosed, and (3) physicians' directiveness in regard to abortion.
      This article discusses results concerning the attitudes and opinions of male and
      female physicians toward prenatal diagnosis, which differed on the three scales.
      Female physicians are more liberal than their male colleagues with regard to
      access to amniocentesis and selective abortion and have a less directive
      relationship with their patients. These tendencies are similar to those observed
      in prior studies. They are particularly marked for general practitioners and
      radiologists. Various explanatory hypotheses are examined.

PMID- 9004374
TI  - Problems in accurate medical diagnosis of depression in female patients.
AB  - Research in women's health has revealed the difficulties female patients
      experience in their attempts to receive accurate medical diagnoses. Depression
      may be misdiagnosed in 30-50% of female patients. This difficulty is considerably
      enhanced when women have physical diseases characterized by symptoms that
      resemble a major depressive disorder. In addition, medical treatments may induce
      symptoms that are misdiagnosed as affective distress. Multiple causes contribute
      to an enhanced likelihood of misdiagnoses in women, including physicians'
      androcentrically orientated medical training and the two-to-one female-to-male
      ratio of depression treatment. The adverse consequences of incorrect diagnoses
      range from unnecessary expenditures of a woman's resources to potentially life
      threatening medical conditions. Ironically, medical misdiagnoses of physical
      conditions may induce depressive reactions in female patients. A woman's age,
      sexual orientation, menstrual, occupational, and/or parental status represent
      potential areas of discrimination in diagnostic determinations. Suggestions are
      offered for improving the accuracy of health care providers' diagnoses in women.

PMID- 9004373
TI  - Direct and buffer effects of social support and personal coping resources in
      individuals with arthritis.
AB  - The direct and buffer effects of various aspects of social support and personal
      coping resources on depressive symptoms were examined. The study concerned a
      community-based sample of 1690 older persons aged 55-85 yrs, of whom 719 had no
      chronic disease, 612 had mild arthritis and 359 had severe arthritis. Persons
      with arthritis reported more depressive symptoms than persons with no chronic
      diseases. Irrespective of arthritis, the presence of a partner, having many close
      social relationships, feelings of mastery and a high self-esteem were found to
      have direct, favourable effects on psychological functioning. Mastery, having
      many diffuse social relationships, and receiving emotional support seem to
      mitigate the influence of arthritis on depressive symptoms, which is in
      conformity with the buffer hypothesis. Favourable effects of these variables on
      depressive symptomatology were only, or more strongly, found in persons suffering
      from severe arthritis.

PMID- 9004375
TI  - Population density and spatial differentials in child mortality in Zimbabwe.
AB  - Large regional variations in under-five mortality exist within many sub-Saharan
      countries. Population density as a potential explanatory factor for these
      regional variations has seldom been considered despite it being implicated as a
      determinant of mortality at other spatial scales. In Zimbabwe, the "Ndebele
      provinces"-Matabeleland North and South-have significantly lower levels of under
      five mortality than the other ("Shona") provinces. This regional differential is
      explored using the Zimbabwe Demographic and Health Survey and census data.
      Factors other than population density that may contribute to the differential are
      examined. After controlling for the effects of potentially confounding socio
      economic, demographic and environmental variables using Cox regression models
      children aged 1-4 yr living in the Ndebele provinces continued to have a level of
      mortality 45% lower than their counterparts in the Shona provinces. The
      possibility that regional variations in health care provision and/or cultural
      factors contribute to the mortality differential is also examined and rejected.
      Population densities in the Ndebele provinces are of a far lower order than in
      the Shona provinces. The main causes of child mortality in Zimbabwe in the time
      period under consideration were diarrhoea, ALRI, measles and malaria. How
      population density may affect the transmission of these infections and, hence,
      mortality is discussed. It is suggested that population density may provide an
      explanation for the spatial variation in child mortality in Zimbabwe. The
      implications of changing population densities for child health in urban and rural
      sub-Saharan Africa are briefly considered.

PMID- 9004376
TI  - Health behaviour and risk behaviour: socioeconomic differences in an Austrian
      rural county.
AB  - The aim of this study is to illustrate the impact of socioeconomic differences on
      two basic kinds of health-related behaviour defined as health behaviour (HB) and
      risk behaviour (RB). We analysed data derived from a health survey on health
      related behaviour and self-reported morbidity in relation to demographic and
      socioeconomic factors. The survey consists of a random sample of 27,344
      individuals taken from 79 communities from the rural population of Styria
      (Austria). Using directly standardised indicators both HB and RB revealed clear
      but inverse associations with education, SES and gender. HB rises and RB falls
      with years of schooling completed. HB is higher in women (103.5 versus 95.0, p <
      0.01) whereas RB is higher in men (128.9 versus 80.1, p < 0.01). Different
      patterns of association with age were found. We conclude that both HB and RB
      should be considered as mediating factors between SES and health status.

PMID- 9004377
TI  - Markov chain Monte Carlo methods in biostatistics.
AB  - Appropriate models in biostatistics are often quite complicated. Such models are
      typically most easily fit using Bayesian methods, which can often be implemented
      using simulation techniques. Markov chain Monte Carlo (MCMC) methods are an
      important set of tools for such simulations. We give an overview and references
      of this rapidly emerging technology along with a relatively simple example. MCMC
      techniques can be viewed as extensions of iterative maximization techniques, but
      with random jumps rather than maximizations at each step. Special care is needed
      when implementing iterative maximization procedures rather than closed-form
      methods, and even more care is needed with iterative simulation procedures: it is
      substantially more difficult to monitor convergence to a distribution than to a
      point. The most reliable implementations of MCMC build upon results from simpler
      models fit using combinations of maximization algorithms and noniterative
      simulations, so that the user has a rough idea of the location and scale of the
      posterior distribution of the quantities of interest under the more complicated
      model. These concerns with implementation, however, should not deter the
      biostatistician from using MCMC methods, but rather help to ensure wise use of
      these powerful techniques.

PMID- 9004378
TI  - Robustness considerations in Bayesian analysis.
AB  - All statistical analyses demand uncertain inputs or assumptions. This is
      especially true of Bayesian analyses. In addition to the usual concerns about the
      agreement of the data and model, a Bayesian must contemplate the effect of an
      uncertain prior specification. The degree to which inferences are robust to
      changes in the prior is of primary interest. This article discusses some robust
      techniques that have been suggested in the literature. One goal is to make
      apparent the relevance of some of these techniques to biostatistical work.

PMID- 9004379
TI  - Bayesian inference for hierarchical mixtures-of-experts with applications to
      regression and classification.
AB  - This paper studies the problems of inference and prediction in a class of models
      known as hierarchical mixtures-of-experts (HME). The statistical model underlying
      an HME is a mixture model in which both the mixture coefficients and the mixture
      components are generalized linear models. Bayesian inference regarding an HME's
      parameters is presented in the contexts of regression and classification using
      Markov chain Monte Carlo methods. A benefit of this Bayesian approach is the
      ability to obtain a sample from the posterior distribution of any functional of
      the parameters of the given model. In this way, more information is obtained than
      provided by a point estimate. The methods are illustrated on a nonlinear
      regression problem and on a breast cancer classification problem. The results
      indicate that the HME showed good prediction performance, and also gave the
      additional benefit of providing for the opportunity to assess the degree of
      certainty of the model in its predictions.

PMID- 9004381
TI  - Non-response models for the analysis of non-monotone non-ignorable missing data.
AB  - I introduce a new class of non-ignorable non-monotone missing data models. These
      models are useful for investigating the sensitivity of one's estimates to
      untestable assumptions about the missing data process. I use the new models to
      analyse data from a case-control study of the effect of radiation on breast
      cancer.

PMID- 9004383
TI  - Some issues in estimating the effect of prognostic factors from incomplete
      covariate data.
AB  - In evaluating prognostic factors by means of regression models, missing values in
      the covariate data are a frequent complication. There exist statistical tools to
      analyse such incomplete data in an efficient manner, and in this paper we make
      use of the traditional maximum likelihood principle. As well as an analysis
      including the incompletely measured covariates, such tools also allow further
      strategies of data analysis. For example, we can use surrogate variables to
      improve the prediction of missing values or we can try to investigate a
      questionable "missing at random' assumption. We discuss these techniques using
      the example of a clinical study where one important covariate is missing for
      about half the subjects. Additionally we consider two further issues: evaluation
      of differences between estimates from a complete case analysis and analyses using
      all subjects and assessment of the predictive value of missing values.

PMID- 9004382
TI  - Non-response models for the analysis of non-monotone ignorable missing data.
AB  - We discuss a new class of ignorable non-monotone missing data models-the
      randomized monotone missingness (RMM) models. We argue that the RMM models
      represent the most general plausible physical mechanism for generating non
      monotone ignorable data. We show that there exists ignorable missing data
      processes that are not RMM. We argue that it may therefore be inappropriate to
      analyse non-monotone missing data under the assumption that the missingness
      mechanism is ignorable, if a statistical test has rejected the hypothesis that
      the missing data process is RMM representable. We use RMM models to analyse data
      from a case-control study of the effects of radiation on breast cancer.

PMID- 9004380
TI  - The relationship between hot-deck multiple imputation and weighted likelihood.
AB  - Hot-deck imputation is an intuitively simple and popular method of accommodating
      incomplete data. Users of the method will often use the usual multiple imputation
      variance estimator which is not appropriate in this case. However, no variance
      expression has yet been derived for this easily implemented method applied to
      missing covariates in regression models. The simple hot-deck method is in fact
      asymptotically equivalent to the mean-score method for the estimation of a
      regression model parameter, so that hot-deck can be understood in the context of
      likelihood methods. Both of these methods accommodate data where missingness may
      depend on the observed variables but not on the unobserved value of the
      incomplete covariate, that is, missing at random (MAR). The asymptotic properties
      of hot-deck are derived here for the case where the fully observed variables are
      categorical, though the incomplete covariate(s) may be continuous. Simulation
      studies indicate that the two methods compare well in small samples and for small
      numbers of imputations. Current users of hot-deck may now conduct their analysis
      using mean-score, which is a weighted likelihood method and can thus be
      implemented by a single pass through the data using any standard package which
      accommodates weighted regression models. Valid inference is now straightforward
      using the variance expression provided here. The equivalence of mean-score and
      hot-deck is illustrated using three clinical data sets where an important
      covariate is missing for a large number of study subjects.

PMID- 9004384
TI  - Probability imputation revisited for prognostic factor studies.
AB  - The analysis of prognostic factor studies by Cox or logistic regression models is
      often impeded by missing covariate values. In 1990 Schemper and Smith recommended
      a conditional probability imputation technique (PIT) for the analysis of
      treatment studies which can be easily applied using standard software and which
      has been demonstrated to outperform the complete case and omission of covariates
      strategies. Recent research, however, showed that PIT cannot universally be
      recommended and it was concluded that model-based methods should be preferred. We
      agree with these conclusions but also think that there is enough empirical
      evidence to judge the performance of PIT to be satisfactory in typical prognostic
      factor studies. Furthermore, comparisons of PIT with multiple imputation in the
      same context did not indicate an advantage of the latter more involved technique.
      By means of an analysis of a prostate cancer data set various aspects of
      application of PIT are discussed, in particular that PIT permits direct
      comparability of marginal and partial effects analyses. We conclude that PIT
      continues to be an appropriate and attractive choice for analyses of prognostic
      factor studies.

PMID- 9004385
TI  - Analysis of semi-parametric regression models with non-ignorable non-response.
AB  - In this article we consider the problem of making inferences about the parameter
      beta zero indexing the conditional mean of an outcome given a vector of
      regressors when a subset of the variables (outcome or covariates) are missing for
      some study subjects and the probability of non-response depends upon both
      observed and unobserved data values, that is, non-response is non-ignorable. We
      propose a new class of inverse probability of censoring weighted estimators that
      are consistent and asymptotically normal (CAN) for estimating beta zero when the
      non-response probabilities can be parametrically modelled and a CAN estimator
      exists. The proposed estimators do not require full specification of the
      likelihood and their computation does not require numerical integration. We show
      that the asymptotic variance of the optimal estimator in our class attains the
      semi-parametric variance bound for the model. In some models, no CAN estimator of
      beta zero exists. We provide a general algorithm for determining when CAN
      estimators of beta zero exist. Our results follow after specializing a general
      representation described in the article for the efficient score and the influence
      function of regular, asymptotically linear estimators in an arbitrary semi
      parametric model with non-ignorable non-response in which the probability of
      observing complete data is bounded away from zero and the non-response
      probabilities can be parametrically modelled.

PMID- 9004387
TI  - Logistic analysis of studies with two-stage sampling: a comparison of four
      approaches.
AB  - This paper discusses the analysis of two-stage studies where covariates are
      missing or measured with error at the first stage of sampling and are validated
      at the second stage in a subsample. Four recently developed approaches, the
      weighted pseudo-likelihood method of Flanders and Greenland (1991), the pseudo
      conditional likelihood methods of Breslow and Cain (1988) and Schill et al.
      (1993) and the maximum likelihood estimate obtained via the EM-algorithm
      (Wacholder and Weinberg, 1994) are reviewed, and some connections between them
      are established. It is shown that, with respect to odds ratio estimation, case
      control designs can be analysed as if first-stage sampling had been prospective.
      The procedures are numerically compared with respect to asymptotic relative
      efficiency in a missing value setting.

PMID- 9004386
TI  - Weighted likelihood, pseudo-likelihood and maximum likelihood methods for
      logistic regression analysis of two-stage data.
AB  - General approaches to the fitting of binary response models to data collected in
      two-stage and other stratified sampling designs include weighted likelihood,
      pseudo-likelihood and full maximum likelihood. In previous work the authors
      developed the large sample theory and methodology for fitting of logistic
      regression models to two-stage case-control data using full maximum likelihood.
      The present paper describes computational algorithms that permit efficient
      estimation of regression coefficients using weighted, pseudo- and full maximum
      likelihood. It also presents results of a simulation study involving continuous
      covariables where maximum likelihood clearly outperformed the other two methods
      and discusses the analysis of data from three bona fide case-control studies that
      illustrate some important relationships among the three methods. A concluding
      section discusses the application of two-stage methods to case-control studies
      with validation subsampling for control of measurement error.

PMID- 9004388
TI  - An approach to estimating exposure-specific rates of breast cancer from a two
      stage case-control study within a cohort.
AB  - The Breast Cancer Detection and Demonstration Project (BCDDP) included a large
      cohort of women followed for incidence of breast cancer and from whom an initial
      case-control sample was drawn and standard risk factors obtained. In order to
      study the effect of mammographic features on breast cancer risk, a nested
      subsample of cases and controls was drawn. Therefore, these data can be viewed as
      two-stage case-control data within a cohort, or as cohort data with two nested
      levels of missingness, since basic characteristics like age were measured on all
      members of the cohort, standard risk factors were elicited only in the initial
      case-control sample, and mammographic features were assessed only in the nested
      subsample of cases and controls. We present a Poisson pseudo-likelihood approach
      to estimating age- and exposure-specific breast cancer incidence rates based on
      the three types of variables. This approach takes into account the nested
      missingness as well as two other type of missingness namely, that for basic
      variables and standard risk factors, some levels (i) were omitted by design in
      the nested subsample of case and controls or (ii) were empty because of the
      sparsity of the data in that subsample. Estimates of standard errors are obtained
      from a parametric bootstrap. The approach seems to be efficient when applied to
      the BCDDP data and is flexible for modelling breast cancer rates and taking the
      special missingness features of these data into account.

PMID- 9004390
TI  - Segmented regression with errors in predictors: semi-parametric and parametric
      methods.
AB  - We consider the estimation of parameters in a particular segmented generalized
      linear model with additive measurement error in predictors, with a focus on
      linear and logistic regression. In epidemiologic studies segmented regression
      models often occur as threshold models, where it is assumed that the exposure has
      no influence on the response up to a possibly unknown threshold. Furthermore, in
      occupational and environmental studies the exposure typically cannot be measured
      exactly. Ignoring this measurement error leads to asymptotically biased
      estimators of the threshold. It is shown that this asymptotic bias is different
      from that observed for estimating standard generalized linear model parameters in
      the presence of measurement error, being both larger and in different directions
      than expected. In most cases considered the threshold is asymptotically
      underestimated. Two standard general methods for correcting for this bias are
      considered; regression calibration and simulation extrapolation (simex). In
      ordinary logistic and linear regression these procedures behave similarly, but in
      the threshold segmented regression model they operate quite differently. The
      regression calibration estimator usually has more bias but less variance than the
      simex estimator. Regression calibration and simex are typically thought of as
      functional methods, also known as semi-parametric methods, because they make no
      assumptions about the distribution of the unobservable covariate X. The
      contrasting structural, parametric maximum likelihood estimate assumes a
      parametric distributional form for X. In ordinary linear regression there is
      typically little difference between structural and functional methods. One of the
      major, surprising findings of our study is that in threshold regression, the
      functional and structural methods differ substantially in their performance. In
      one of our simulations, approximately consistent functional estimates can be as
      much as 25 times more variable than the maximum likelihood estimate for a
      properly specified parametric model. Structural (parametric) modelling ought not
      be a neglected tool in measurement error models. An example involving dust
      concentration and bronchitis in a mechanical engineering plant in Munich is used
      to illustrate the results.

PMID- 9004389
TI  - Multi-stage sampling in genetic epidemiology.
AB  - When data are expensive to collect, it can be cost-efficient to sample in two or
      more stages. In the first stage a simple random sample is drawn and then
      stratified according to some easily measured attribute. In each subsequent stage
      a random subset of previously selected units is sampled for more detailed
      observation, with a unit's sampling probability determined by its attributes as
      observed in the previous stages. These designs are useful in many medical
      studies; here we use them in genetic epidemiology. Two genetic studies illustrate
      the strengths and limitations of the approach. The first study evaluates nuclear
      and mitochondrial DNA in U.S. blacks. The goal is to estimate the relative
      contributions of white male genes and white female genes to the gene pool of
      African-Americans. This example shows that the Horvitz-Thompson estimators
      proposed for multi-stage designs can be inefficient, particularly when used with
      unnecessary stratification. The second example is a multi-stage study of familial
      prostate cancer. The goal is to gather pedigrees, blood samples and archived
      tissue for segregation and linkage analysis of familial prostate cancer data by
      first obtaining crude family data from prostate cancer cases and cancer-free
      controls. This second example shows the gains in efficiency from multi-stage
      sampling when the individual likelihood or quasilikelihood scores vary
      substantially across strata.

PMID- 9004391
TI  - Estimation by data augmentation in regression models with continuous and discrete
      covariates measured with error.
AB  - Estimation methods are considered for regression models which have both
      misclassified discrete covariates and continuous covariates measured with error.
      Adjusted parameter estimates are obtained using the method of data augmentation,
      where the true values of the covariates measured with error are regarded as
      missing data. Validation data on the covariates are assumed to be available. The
      distinction between internal and external validation data is emphasized, and its
      effects on the analysis are examined. The method is illustrated with simulated
      data.

PMID- 9004392
TI  - Some comments on misspecification of priors in Bayesian modelling of measurement
      error problems.
AB  - In this paper we discuss some aspects of misspecification of prior distributions
      in the context of Bayesian modelling of measurement error problems. A Bayesian
      approach to the treatment of common measurement error situations encountered in
      epidemiology has been recently proposed. Its implementation involves, first, the
      structural specification, through conditional independence relationships, of
      three submodels-a measurement model, an exposure model and a disease model- and
      secondly, the choice of functional forms for the distributions involved in the
      submodels. We present some results indicating how the estimation of the
      regression parameters of interest, which is carried out using Gibbs sampling, can
      be influenced by a misspecification of the parametric shape of the prior
      distribution of exposure.

PMID- 9004393
TI  - The role of frailty models and accelerated failure time models in describing
      heterogeneity due to omitted covariates.
AB  - In survival analysis, deviations from proportional hazards may sometimes be
      explained by unaccounted random heterogeneity, or frailty. This paper recalls the
      literature on omitted covariates in survival analysis and shows in a case study
      how unstably frailty models might behave when asked to account for unobserved
      heterogeneity in standard survival analysis with no replications per
      heterogeneity unit. Accelerated failure time modelling seems to avoid these
      difficulties and also to yield easily interpretable results. We propose that it
      would be advantageous to upgrade the accelerated failure time approach alongside
      the hazard modelling approach to survival analysis.

PMID- 9004394
TI  - Effects of covariate omission and categorization when analysing randomized trials
      with the Cox model.
AB  - When analysing the survival of patients in comparative randomized clinical trials
      using the Cox proportional hazards model, important prognostic factors may be
      included for the adjustment of the treatment effect. In this paper we examine two
      of the most common misspecifications of the model: (i) an important prognostic
      factor is omitted from the analysis; and (ii) an important prognostic factor
      originally present on continuous scale is included in categorized form. Both
      situations may emerge from the occurrence of missing values. We investigate the
      properties of the maximum partial likelihood estimator of the treatment effect
      under this kind of misspecification. The estimate of the treatment effect is
      found to be asymptotically biased toward zero. For its asymptotic variance we
      obtain a quantity with the so-called 'sandwich' structure. Thus, variance
      estimation by the inverse of the second-order derivative of the likelihood is not
      consistent. The magnitude of overestimation or underestimation is evaluated
      numerically for specific settings. The precision of the treatment effect estimate
      under covariate omission or categorization is compared with the precision of the
      estimate in the correct and not misspecified model. It turns out that correct
      adjustment does not lead to a higher precision of the treatment effect estimate,
      but due to the resulting underestimation, covariate omission or categorization
      lead to loss of power of the test of no treatment effect.

PMID- 9004396
TI  - Model-based approaches to analysing incomplete longitudinal and failure time
      data.
AB  - Since Wu and Carroll (Biometrics 44, 175-188) proposed a model for longitudinal
      progression in the presence of informative dropout, several researchers have
      developed and studied models for situations where both a vector of repeated
      outcomes and an event time is available for each subject. These models have been
      developed for either longitudinal studies with dropout or for survival studies in
      which a random, time-varying covariate is measured repeatedly across time. When
      inference about the longitudinal variable is of interest, event times are treated
      as covariates and are often incomplete due to censoring. If survival or event
      time is the primary endpoint, repeated outcomes observed prior to the event are
      viewed as covariates; this covariate process is often incomplete, measured with
      error, or observed at unscheduled times during the study. We review several
      models which are used to handle incomplete response and covariate data in both
      survival and longitudinal studies.

PMID- 9004395
TI  - Mixture models for the joint distribution of repeated measures and event times.
AB  - Many long-term clinical trials collect both a vector of repeated measurements and
      an event time on each subject; often, the two outcomes are dependent. One example
      is the use of surrogate markers to predict disease onset or survival. Another is
      longitudinal trials which have outcome-related dropout. We describe a mixture
      model for the joint distribution which accommodates incomplete repeated measures
      and right-censored event times, and provide methods for full maximum likelihood
      estimation. The methods are illustrated through analysis of data from a clinical
      trial for a new schizophrenia therapy; in the trial, dropout time is closely
      related to outcome, and the dropout process differs between treatments. The
      parameter estimates from the model are used to make a treatment comparison after
      adjusting for the effects of dropout. An added benefit of the analysis is that it
      permits using the repeated measures to increase efficiency of estimates of the
      event time distribution.

PMID- 9004397
TI  - The Manton-Woodbury model for longitudinal data with dropouts.
AB  - Often in longitudinal studies one is not able to obtain a complete set of
      measurements of the variable recorded over time for each person in the study.
      This could be caused by some of the persons dying (or leaving the study for some
      other reasons) while the study is going on. If there is any concern that such
      missing data (which have been termed dropouts) and the variables measured over
      time affect each other, a model for the joint distribution is needed. For a
      review of several such models see Hogan and Laird (in this volume). A model of
      the same kind was proposed by Woodbury and Manton and developed further later on.
      In this model it is possible to describe the evolution of the distribution of the
      variable measured over time when exposed to mortality selection. In contrast to
      other models, this allows for an explicit description of the interaction between
      the variable measured over time and the time to dropout. We describe the model
      and propose some generalizations. The theory is illustrated by some Monte Carlo
      simulations.

PMID- 9004398
TI  - Toward a curse of dimensionality appropriate (CODA) asymptotic theory for semi
      parametric models.
AB  - We argue, that due to the curse of dimensionality, there are major difficulties
      with any pure or smoothed likelihood-based method of inference in designed
      studies with randomly missing data when missingness depends on a high-dimensional
      vector of variables. We study in detail a semi-parametric superpopulation version
      of continuously stratified random sampling. We show that all estimators of the
      population mean that are uniformly consistent or that achieve an algebraic rate
      of convergence, no matter how slow, require the use of the selection
      (randomization) probabilities. We argue that, in contrast to likelihood methods
      which ignore these probabilities, inverse selection probability weighted
      estimators continue to perform well achieving uniform n 1/2-rates of convergence.
      We propose a curse of dimensionality appropriate (CODA) asymptotic theory for
      inference in non- and semi-parametric models in an attempt to formalize our
      arguments. We discuss whether our results constitute a fatal blow to the
      likelihood principle and study the attitude toward these that a committed
      subjective Bayesian would adopt. Finally, we apply our CODA theory to analyse the
      effect of the 'curse of dimensionality' in several interesting semi-parametric
      models, including a model for a two-armed randomized trial with randomization
      probabilities depending on a vector of continuous pretreatment covariates X. We
      provide substantive settings under which a subjective Bayesian would ignore the
      randomization probabilities in analysing the trial data. We then show that any
      statistician who ignores the randomization probabilities is unable to construct
      nominal 95 per cent confidence intervals for the true treatment effect that have
      both: (i) an expected length which goes to zero with increasing sample size; and
      (ii) a guaranteed expected actual coverage rate of at least 95 per cent over the
      ensemble of trials analysed by the statistician during his or her lifetime.
      However, we derive a new interval estimator, depending on the Randomization
      probabilities, that satisfies (i) and (ii).

PMID- 9004400
TI  - Meningococcal disease: epidemiology and pathogenesis.

PMID- 9004399
TI  - The inner workings of a quorum sensing signal generator.

PMID- 9004401
TI  - Understanding the role of Th1/Th2 cells in infection.

PMID- 9004402
TI  - Pili, peptidases and protein secretion: curious connections.

PMID- 9004403
TI  - Biological nitrogen fixation for sustainable agriculture.

PMID- 9004404
TI  - BaEV is a relic from an ancient retrovirus that crossed species barriers.

PMID- 9004405
TI  - Pararetro- and retrovirus RNA: splicing and the control of nuclear export.
AB  - Splicing and nuclear export of RNA are obligatory steps in gene expression by
      eukaryotic cells. Not only have novel splicing events been identified during the
      replication cycle of retro- and pararetroviruses, but the resulting combination
      of spliced and unspliced products requires specialized mechanisms for nuclear
      export, which in turn is a key regulatory step for virus replication.

PMID- 9004406
TI  - Psoriasis and bacterial superantigens--formal or causal correlation?
AB  - Superantigens have recently been identified as candidates for triggering crucial
      events in the development of psoriasis. Seemingly contradictory observations may
      complement each other when discussed in the context of the concept of an effector
      cell cascade initiated by bacterial superantigens that eventually brings about
      disruption of peripheral tolerance of a CD8+ T-cell subset.

PMID- 9004407
TI  - Pseudomonas aeruginosa lipopolysaccharides and pathogenesis.
AB  - Pseudomonas aeruginosa lipopolysaccharide (LPS) plays a key role in pathogenesis.
      In acute infections, a smooth LPS protects the organism from complement-mediated
      killing and, during chronic lung infections, an altered rough LPS helps the
      organism evade host defense mechanisms.

PMID- 9004408
TI  - Bacterial polysaccharide synthesis and gene nomenclature.
AB  - Gene nomenclature for bacterial surface polysaccharides is complicated by the
      large number of structures and genes. We propose a scheme applicable to all
      species that distinguishes different classes of genes, provides a single name for
      all genes of a given function and greatly facilitates comparative studies.

PMID- 9004409
TI  - Neurotrophic factors in action--new dogs and new tricks.

PMID- 9004410
TI  - Genetic analysis of axon guidance and mapping in the zebrafish.
AB  - Systematic genetic screens have been powerful tools in identifying genes
      responsible for axon guidance in fruitflies and nematodes. This approach has now
      been extended to the study of axon guidance and the formation of topographic
      neuronal connections in the vertebrate brain. A systematic genetic screen was
      used to identify genes responsible for precise axon pathfinding and targeting in
      the retinotectal system of the zebrafish (Danio rerio). Over 30 genes were found
      that affect either: (1) retinal axon pathfinding to the contralateral tectal
      lobe; or (2) the topographic connection between the eye and the tectum. The
      zebrafish retinotectal mutants represent a new resource for the study of axon
      guidance in the vertebrate brain.

PMID- 9004413
TI  - Is EAG the answer to the M-current?
AB  - The resemblance between the Drosophila EAG current and the mammalian M-current is
      very strong, but final confirmation for a member of the extended EAG family
      encoding the M-current remains to be determined.

PMID- 9004412
TI  - A physiological role for ether-a-go-go K+ channels?

PMID- 9004415
TI  - Another variety of vision.

PMID- 9004414
TI  - Genes at the junction--candidates for congenital myasthenic syndromes.
AB  - The neuromuscular junction is the site of several myasthenic (mys, muscle;
      aesthenia, weakness) disorders of autoimmune and genetic origin. The acquired
      autoimmune conditions are mainly adult-onset and caused by antibodies to specific
      neuronal and muscle ion channels, but can occur neonatally due to placental
      transfer of maternal antibodies. This review focuses on the rarer genetic
      conditions, called congenital myasthenic syndromes (CMS), that often present at
      birth. Mutations have yet to be characterized for familial infantile myasthenia,
      acetylcholinesterase deficiency and ACh-receptor deficiency; but genes encoding
      both structural and functional NMJ protiens should be considered. Other syndromes
      have recently been shown to involve defects in the functioning of the ACh
      receptor itself. In particular, eight different mutations have been reported in
      cases of the slow channel syndrome, a dominant condition associated with point
      mutations that generate single amino acid changes within the ACh receptor and
      result in prolonged channel activations. These investigations are providing new
      insights into the structure and function of the ACh receptor. Further studies of
      CMS should pave the way for analysis and treatment of disorders involving other
      synapses in the peripheral and central nervous system.

PMID- 9004411
TI  - Glutamate receptors of the kainate type and synaptic transmission.
AB  - Glutamic acid is an important excitatory neurotransmitter in the mammalian CNS.
      It has been established that synaptic transmission is mediated mostly by the
      ionotropic glutamate receptors AMPA and NMDA, with fast and slow kinetics,
      respectively. The recent demonstration in hippocampal neurones of a class of
      glutamate receptors that are activated by kainate and not by AMPA (that is,
      kainate-selective receptors) opens the possibility that receptors, others than
      those of the AMPA type, might also be involved in fast neurotransmission. The
      lack of specific pharmacological tools to dissect out AMPA from kainate receptors
      has hampered the functional study of kainate receptors. However, the recent
      finding that a 2,3-benzodiazepine (GYK153655) behaves as a selective antagonist
      of AMPA receptors allows us to address the question of the role of rapidly
      inactivating kainate receptors in synaptic transmission.

PMID- 9004416
TI  - The extracellular matrix in neural crest-cell migration.
AB  - The peripheral nervous system is created by a spatiotemporally co-ordinated
      migratory process during which the precursor cells, the neural crest (NC) cells,
      transverse the embryo to reach distantly located sites. Original transplantation
      experiments implicated the extracellular matrix (ECM) as a pivotal factor in the
      regulation of this process, and subsequent in vitro and in vivo studies have
      uncovered a number of ECM molecules potentially responsible for the NC cell-ECM
      interaction. Recent genetic manipulations in mice sustain the importance of
      certain matrix constituents, while precluding a significant role for others and,
      surprisingly, for all primary integrin receptors expressed by NC cells. The
      gradually crystallizing paradigm envisions that guidance of the disseminating NC
      cells, as well as the arrest at their final tissue locations, is governed by
      specific 'inhibitory' ECM-associated signals. This implies that homing of
      peripheral neurons and their supportive cells might be dictated by a delicate
      equilibrium between the multiple actions of stimulatory and inhibitory molecules,
      which is modulated further by defined responses of the dispersing cells to these
      ECM components during their successive phases of phenotypic diversification.

PMID- 9004417
TI  - Dopamine-cell depolarization block as a model for the therapeutic actions of
      antipsychotic drugs.
AB  - Antipsychotic drugs used in the treatment of schizophrenia have in common the
      property of being dopamine-receptor antagonists. However, the rapid timecourse of
      receptor blockade produced upon drug administration does not correlate with the
      emergence of clinical actions, which typically require weeks of treatment to
      become manifest. Studies in rats have shown that repeated antipsychotic drug
      treatment results in a delayed inactivation of dopamine-neuron firing in the
      midbrain due to depolarization block. Furthermore, the therapeutic efficacy of
      antipsychotic drugs in humans correlates with their ability to induce
      depolarization block of mesolimbic dopamine neurons, whereas their potential to
      produce extrapyramidal side effects correlates with their propensity for inducing
      depolarization block in the nigrostriatal dopamine system. Therefore, dopamine
      cell depolarization block is an effective model for evaluating antipsychotic drug
      efficacy, and provides a potential mechanism to account for their therapeutic
      impact on a dysregulated dopamine system.

PMID- 9004418
TI  - Bursts as a unit of neural information: making unreliable synapses reliable.
AB  - Several lines of evidence indicate that brief (< 25 ms) bursts of high-frequency
      firing have special importance in brain function. Recent work shows that many
      central synapses are surprisingly unreliable at signaling the arrival of single
      presynaptic action potentials to the postsynaptic neuron. However, bursts are
      reliably signaled because transmitter release is facilitated. Thus, these
      synapses can be viewed as filters that transmit bursts, but filter out single
      spikes. Bursts appear to have a special role in synaptic plasticity and
      information processing. In the hippocampus, a single burst can produce long-term
      synaptic modifications. In brain structures whose computational role is known,
      action potentials that arrive in bursts provide more-precise information than
      action potentials that arrive singly. These results, and the requirement for
      multiple inputs to fire a cell suggest that the best stimulus for exciting a cell
      (that is, a neural code) is coincident bursts.

PMID- 9004420
TI  - Imaging of the elastic properties of tissue--a review.
AB  - Recently, a number of methods have been developed that make it possible to image
      the elastic properties of soft tissues. Because certain types of tissues such as
      malignant lesions, for example, have elastic properties that are markedly
      different from surrounding tissues, elasticity imaging could provide a
      significant adjunct to current diagnostic ultrasonic methods. Further, elasticity
      imaging techniques could be used to augment the study of tissues that change
      their elastic properties, such as skeletal and cardiac muscle. In this paper, we
      survey some of the previous work done in the related field of biomechanics, and
      we review measurement techniques from the 1950s to the 1980s. Different
      approaches to elastic imaging and signal processing are then discussed and a
      lexicography for elastic imaging is introduced. It is hoped that this
      nomenclature will provide a meaningful categorization of various approaches and
      will make evident the inherent parameters displayed and conditions applied in
      deriving the resulting images. Key assumptions and signal processing approaches
      are also reviewed. Finally, directions for future work are suggested.

PMID- 9004421
TI  - Fetal echocardiography in three and four dimensions.
AB  - A three-dimensional (3D) acquisition system using an electromagnetic position
      sensor attached to a standard transducer on an unmodified ultrasound scanner was
      developed to capture two-dimensional (2D)-fetal echocardiograms at various
      positions and orientations. Operating in real-time directed M-mode allowed
      recording of 2D structural images and cardiac motion curves, from which the fetal
      cardiac phase could be determined. By digitising over 100 image frames for each
      scanning sequence, and by selecting frames at particular phases, 3D views of the
      fetal heart were reconstructed for each phase. Of 20 sequences of six fetuses
      scanned, 13 sequences successfully demonstrated usable 3D fetal heart structures,
      including four cardiac chambers, ventricular and atrial septa, foramen ovale and
      some of the cardiac valves and great vessels. Rearrangement of those phased 3D
      images into a cyclic sequence could generate dynamic 3D views of a beating fetal
      heart. We believe that, with further technical development, this new approach
      will be of use in the diagnosis of prenatal cardiac malformations and
      malfunctions, in in utero cardiac surgery and in fetal cardiology teaching.

PMID- 9004419
TI  - Human cortical oscillations: a neuromagnetic view through the skull.
AB  - The mammalian cerebral cortex generates a variety of rhythmic oscillations,
      detectable directly from the cortex or the scalp. Recent non-invasive recordings
      from intact humans, by means of neuromagnetometers with large sensor arrays, have
      shown that several regions of the healthy human cortex have their own intrinsic
      rhythms, typically 8-40 Hz in frequency, with modality- and frequency-specific
      reactivity. The conventional hypotheses about the functional significance of
      brain rhythms extend from epiphenomena to perceptual binding and object
      segmentation. Recent data indicate that some cortical rhythms can be related to
      periodic activity of peripheral sensor and effector organs.

PMID- 9004423
TI  - In vitro validation of intravascular ultrasound imaging after balloon angioplasty
      of coronary artery stenoses.
AB  - Systematic studies of intravascular ultrasound imaging of in vitro balloon
      angioplasty on coronary arteries with a greater than 50% diameter stenosis on
      angiogram have not been performed. We used 23 plasma-perfused postmortem human
      coronary arteries with an angiographic diameter stenosis of > or = 50%. After
      balloon dilation the vessels were examined by 30-MHz intravascular ultrasound
      imaging (IVUS) and the presence of ruptures and dissections was noted. Ruptures
      were defined as disruptions of the vessel wall in a radial direction, and
      dissections were defined as disruptions in a circumferential direction. After
      pressure fixation they were studied by histology. On IVUS, 24 vessel wall
      disruptions were diagnosed in 14 arteries. On histology, 29 disruptions were
      diagnosed in 19 arteries. The sensitivity of IVUS for the detection of
      disruptions was 79%, the specificity was 75%. Total agreement was 79%. Accuracy
      was better for dissections (total agreement 96%) than for ruptures (total
      agreement 74%). Shadowing behind calcium and close contact of the catheter to the
      arterial wall were important sources of error in the IVUS analysis. We conclude
      that intravascular ultrasound imaging is accurate for the detection of
      disruptions after balloon angioplasty of angiographically significant coronary
      artery stenoses.

PMID- 9004422
TI  - Ultrasonic measurement of glomerular diameters in normal adult humans.
AB  - The average size of acoustic scatterers and the integrated backscatter
      coefficient of kidney cortex were measured in vivo from 2-4 MHz for a group of 50
      normal adult volunteers. Our goal was to determine the sensitivity of the
      ultrasonic measurements under clinical conditions by identifying biologic sources
      of estimation uncertainty. Based on 10 measurements on each kidney of each
      volunteer, the average glomerular diameter for the group was found to be 216 +/-
      27 microns (SD). Glomerular size was found to correlate with body surface area (r
      = 0.4), and the ratio of glomerular surface area to body surface area (GSA/BSA)
      was found to be constant throughout normal adult life with GSA/BSA = (8.24 +/-
      1.35) x 10(-8) (SD). These results are consistent with histologic analyses found
      in the literature. Within an individual, 7% standard errors in GSA/BSA are
      typical. Biologic variability dominates the variance in scatterer size estimates
      in a group not matched for BSA, where it accounts for 47% of the variance. In a
      group of individuals matched for BSA, biologic variability accounts for only 21%
      of the variance; day-to-day variability accounts for 35% of the variance; and
      experimental parameters account for the remainder. If a deviation greater than 2
      x SD is considered abnormal, then this technique can potentially detect changes
      in glomerular diameter as small as 30 microns within an individual. To detect
      abnormal GSA/BSA values for an individual, GSA/BSA would have to differ from the
      mean for that group by about 3.6 x 10(-8) or about 40%. Therefore, at this time
      scatterer size estimates appear most reliable for tracking the progression of
      disease and treatment for an individual over time.

PMID- 9004424
TI  - An in vitro evaluation of the line pattern of the near and far walls of carotid
      arteries using B-mode ultrasound.
AB  - This in vitro study was executed to evaluate the double line pattern generated at
      both near and far walls of human carotid arteries using B-mode ultrasound.
      Therefore, extravascular (7.5 MHz) and intravascular (30 MHz) ultrasound imaging
      were performed at the same locations of the carotid artery. The thickness of the
      double line pattern of the extravascular image (7.5 MHz) was compared to the
      thickness of the intima-media complex seen on the corresponding intravascular
      image (30 MHz) and on the histologic section. At the far wall of the
      extravascular image, the measurements were executed at the leading edge of the
      echo. The data showed high correlation and agreement with the intravascular (r =
      0.91, p < 0.001; mean(diff) = -0.01 and SDdiff = 0.12) and the histologic
      measurements (r = 0.87, p < 0.001; mean(diff) = -0.12 and SDdiff = 0.13). In
      addition, the results of the measurements of the intravascular image showed high
      correlations and agreement with the histologic data (r(near) = 0.86, p < 0.001;
      mean(diff) = -0.08 and SDdiff = 0.15, respectively, r(far) = 0.92, p < 0.001;
      mean(diff) = -0.12 and SDdiff = 0.12). For comparison with other studies, near
      wall measurements were also included. These had to be performed at the trailing
      edge of the echoes to be compatible with these studies. The results of the
      measurements of the extravascular image showed poor correlations and lack of
      agreement with those of the intravascular (r = 0.49, p = 0.03; mean(diff) = 0.09
      and SDdiff = 0.25) and of the histologic (r = 0.37, p = 0.03; mean(diff) = 0.04
      and SDdiff = 0.23) measurements. These results can easily be explained from the
      physical limitations of measuring at the trailing edges. We conclude that the
      double line pattern seen at the far wall of the extravascular image is
      representative of the intima-media complex.

PMID- 9004425
TI  - Computational analysis of the ductus venosus fluid dynamics based on Doppler
      measurements.
AB  - The simplified Bernoulli equation is currently used to evaluate pressure
      gradients on the basis of Doppler velocity measurements when direct pressure data
      require highly invasive procedures. Recently, this method was applied to the
      ductus venosus (DV) in order to estimate the fetal central venous pressure. The
      complex geometry- and consequently hemodynamics-of this fetal region suggests
      caution in automatically converting Doppler velocity measurements to pressure
      data. To investigate the reliability of the Bernoulli equation for this practice,
      we simulated the hemodynamics of the branching between the umbilical vein (UV)
      and the DV on the basis of ultrasonographic data from a normal fetus, using a
      simplified parametric 3D numerical model of a bent tube with varying cross
      section (UV) and a smaller trumpet-shaped branch (DV). A finite element
      formulation has been adopted to solve the governing Navier-Stokes equations. The
      results show that the simplified Bernoulli equation, despite of its simplicity,
      provides a good estimation of the pressure drop between the UV and the DV outlet
      section (with an error of about 0.25 mmHg, equal to 15%, compared with the model
      results). Nevertheless, attention must be paid to the velocity measurement sites,
      as discussed in this paper. In turn, the error becomes notable (2.8 mmHg, i.e.,
      34%) for high velocity values, thus suggesting that the error in evaluating the
      pressure drop with the simplified Bernoulli equation during fetal inspiratory
      movements may be substantial.

PMID- 9004426
TI  - Differentiation between emboli and artefacts using dual-gated transcranial
      Doppler ultrasound.
AB  - It is well documented that transcranial Doppler ultrasound has the ability to
      detect cerebral emboli. During intraoperative patient monitoring studies, many
      signals due to artefact (probe motion, patient movement or surgical manipulation)
      are also detected and can be difficult to distinguish from genuine embolic
      events. We have constructed a Doppler system that can simultaneously range-gate
      at two separate depths, in order to test the hypothesis that it should be
      possible to distinguish between emboli and artefact by comparing the signal from
      the two separate regions within the vessel. The classification algorithm is based
      on the principle that emboli propagate with blood motion (whereas artefacts do
      not) and thus will be detected sequentially at different depths along the
      insonated cerebral artery. One hundred thirty-eight (presumed) embolic and 170
      artefact signals were analysed. The median (interquartile range) gate separation
      was 10.01 mm (7.41-10.78 mm). The time delay between detection of embolic signals
      in the two channels was 11.04 ms (6.24-16.41 ms, but was only 0.08 ms (-0.48(
      )+0.64 ms) for artefact (p < 0.0001). Dual-gated Doppler ultrasound is a
      conclusive and independent method that differentiates emboli from artefact.
      Incorporation of this system for long-term monitoring may eliminate the need for
      an experienced observer to be present.

PMID- 9004427
TI  - Pharmacokinetic studies of different echo-contrast agents in the cerebral
      circulation of dogs.
AB  - Ultrasound contrast agents (UCAs) are improving the signal-to-noise ratio of the
      reflected ultrasound so that Doppler frequency spectra can be recorded even under
      poor sonographic conditions. This is of particular diagnostic value in
      transcranial Doppler sonography. Depending on specific pharmacologic properties,
      echo-contrast agents may cause different increase and duration in Doppler signal
      amplitude. We used a dog model to study the temporal profile of Doppler signal
      amplitude after application of a phospholipid-containing echo-contrast agent (BY
      963). In addition, we compared it with a contrast agent containing albumin
      (Albunex). Spherosome suspension BY 963 resulted in a dose-dependent increase in
      the duration of ultrasound amplification (Doppler enhancement of 1 mL, 3 mL and
      10 mL of BY 963 per animal: 62.4 +/- 8.4, 72.8 +/- 9.2 and 67.7 +/- 4.2 s,
      respectively, n = 6). Detection of BY 963 in the extracranial jugular vein
      demonstrated that the UCA passes through the cerebral microcirculation (cerebral
      transit time was 2.2 +/- 0.2 s, n = 4). The signal enhancement lasted longer
      using the spherosome suspension compared with the albumin-containing solution
      (77.2 +/- 11.6 and 31.1 +/- 3.7 s, respectively, n = 6), and the maximum increase
      in intensity was more pronounced (27.0 +/- 2.0 and 17.5 +/- 2.2 dB, respectively,
      n = 6).

PMID- 9004429
TI  - Autocorrelation of integrated power Doppler signals and its application.
AB  - The integrated power Doppler signal arising from blood flow is a random process.
      In this article, a general approach to model this random process is studied. Both
      the theoretical and experimental results show that the temporal autocorrelation
      function of the integrated power Doppler signals is directly related to
      properties of the insonified medium, such as the scattering strengths and
      velocities of all moving scatterers, and as well as the properties of the Doppler
      imaging system, such as the point spread function (psf) of the power Doppler
      images. Some initial experiments are performed to test the proposed model. Its
      potential application for flow measurement, such as perfusion evaluation, is also
      discussed.

PMID- 9004428
TI  - Noise reduction in elastograms using temporal stretching with multicompression
      averaging.
AB  - Elastography uses estimates of the time delay (obtained by cross-correlation) to
      compute strain estimates in tissue due to quasistatic compression. Because the
      time delay estimates do not generally occur at the sampling intervals, the
      location of the cross-correlation peak does not give an accurate estimate of the
      time delay. Sampling errors in the time-delay estimate are reduced using signal
      interpolation techniques to obtain subsample time-delay estimates. Distortions of
      the echo signals due to tissue compression introduce correlation artifacts in the
      elastogram. These artifacts are reduced by a combination of small compressions
      and temporal stretching of the postcompression signal. Random noise effects in
      the resulting elastograms are reduced by averaging several elastograms, obtained
      from successive small compressions (assuming that the errors are uncorrelated).
      Multicompression averaging with temporal stretching is shown to increase the
      signal-to-noise ratio in the elastogram by an order of magnitude, without
      sacrificing sensitivity, resolution or dynamic range. The strain filter concept
      is extended in this article to theoretically characterize the performance of
      multicompression averaging with temporal stretching.

PMID- 9004430
TI  - Three-dimensional power Doppler imaging: a phantom study to quantify vessel
      stenosis.
AB  - This study investigated whether three-dimensional (3D) power Doppler imaging can
      be used to quantify arterial stenosis and its potential as an alternative to x
      ray angiography. Three-dimensional power Doppler images of in vitro stenotic
      vessels were generated under different hemodynamic conditions with a 3D power
      Doppler imaging system. This system includes: a Macintosh Quadra 840AV computer
      used to perform 3D imaging acquisition, reconstruction and display; a computer
      controlled motor-driven translation assembly used to move the transducer; and an
      ATL Ultramark 9 HDI ultrasound system. Three vascular- and tissue-mimicking
      phantoms containing three wall-less stenotic vessels with area reduction of 80%,
      50% and 30% were imaged with different flow rates under both steady and pulsatile
      flow conditions and with different Doppler angles under steady flow condition.
      With the use of the blood mimic, experimental results demonstrated that power
      Doppler imaging is nearly independent on flow velocity and Doppler angle. It was
      also demonstrated that 3D power Doppler imaging can produce nonpulsatile
      angiographic-like 3D images of the flow field. The stenotic vessels were
      quantified with an overall accuracy of 8.3% of the vessel area and an overall
      precision of 7% of the vessel area under the conditions described in this paper.
      It is believed that 3D power Doppler imaging can be used to quantify arterial
      stenosis, and in some applications it could be an alternative to x-ray
      angiography.

PMID- 9004431
TI  - Noninvasive arterial occlusion using MRI-guided focused ultrasound.
AB  - The purpose of this work was to test the hypothesis that reproducible and
      sustainable arterial occlusion can be induced by focused ultrasound energy
      deposition noninvasively within deep tissue. An MRI-compatible focused ultrasound
      transducer was used to sonicate a branch of the renal artery (diameter about 0.6
      mm) in vivo (nine rabbits). An intravenous MRI contrast agent bolus was injected
      about 30 min and up to 7 days after the sonication. After follow-up, in vitro
      magnification x-ray angiograms were obtained and the kidneys were fixed in
      formaldehyde for histologic study. The ultrasound pulses resulted in complete
      cessation of blood flow, as shown by the gradient echo images. In seven of the
      nine rabbits, a wedge-shaped unenhanced area was seen at the part of the kidney
      that was perfused by the vessel after the contrast agent injection. This area
      extended laterally (outside of the sonicated volume) to the cortical surface of
      the kidney. The x-ray angiograms showed that the artery was completely occluded.
      Postmortem histologic evaluation showed an infarcted tissue volume corresponding
      to the wedge shape seen in the images. This study showed that appropriately
      focused ultrasound can be used to close arteries noninvasively. This finding has
      significant clinical potential.

PMID- 9004432
TI  - Detection of acoustic emission from cavitation in tissue during clinical
      extracorporeal lithotripsy.
AB  - A 1-MHz focused hydrophone has been used to search for acoustic emission expected
      to arise from cavitation occurring in tissue during clinical extracorporeal shock
      wave lithotripsy (ESWL). The hydrophone is acoustically coupled to the patient's
      skin and the focus directed at depth in tissue under ultrasound guidance. The
      measured amplitude-time variation of the acoustic emission from tissue near the
      shock-wave focus of the Storz Modulith SL20 lithotripter has been examined in
      four patients. There is evidence of increased amplitude acoustic emission at 1
      MHz from regions within tissue that also appear hyperechoic in simultaneously
      acquired ultrasound images. The acoustic emission from these regions decays from
      an initial peak to the noise level in about 500 microseconds following each shock
      wave pulse. Within this period, a second peak, often of higher amplitude than the
      first, is typically observed about 100 microseconds after the shockwave. The time
      between the initial and second peaks is found to increase with increasing shock
      wave amplitude. The results are similar to those previously observed from
      cavitation induced by shock-wave exposure in water and indicate that the 1-MHz
      acoustic emission arises from inertial cavitation in tissue during clinical ESWL.

PMID- 9004433
TI  - Contrast-agent gas bodies enhance hemolysis induced by lithotripter shock waves
      and high-intensity focused ultrasound in whole blood.
AB  - Fresh canine whole blood was exposed in 1.3-mL disposable pipette bulbs with or
      without added Albunex contrast agent to lithotripter shock waves (rate: 2 Hz;
      mean pressure amplitude: 14.8 MPa) or 1.28-MHz high-intensity focused ultrasound
      up to a mean pressure amplitude of 17.8 MPa. Significant shock-wave-induced
      hemolysis up to about 10% was detected after 500 or more shock waves without
      added agent, after 200 with 1% added agent and after 100 with 10% added contrast
      agent. Hemolysis was increased somewhat with added contrast agent, but this
      enhancement was not statistically significant. For ultrasound exposure,
      significant hemolysis approaching 100% was detected for 100-ms continuous
      exposure at 17.8 MPa without added gas bodies. Addition of 1% contrast agent
      enhanced the hemolysis by reducing the apparent threshold to 10 MPa. Burst mode
      exposure with a 100-ms total on-time (20 microseconds, 100 microseconds and 1-ms
      bursts) also yielded hemolysis enhancement with added contrast agent, with
      results similar to the 100-ms continuous exposure. The added gas bodies appear to
      lower cavitation thresholds by serving as cavitation nuclei in the blood.

PMID- 9004434
TI  - The combined effects of high-energy shock waves and ionising radiation on a human
      bladder cancer cell line.
AB  - The effects of high-energy shock waves (HESW) generated by an experimental
      Siemens lithotripter in combination with 137Cs gamma-rays were examined in vitro.
      Proliferation after treatment of immobilised pellets of either single cells or
      multicellular spheroids of the bladder cancer cell line RT4 was determined using
      colony-forming assays and cell cycle analysis. Surviving and cell cycle fractions
      were calculated for each shock wave and radiation application mode separately,
      and for sequential combination in different successions for the purpose of
      characterizing the interaction of both treatment modalities. Combination of HESW
      and ionising radiation turned out to act additively or slightly supra-additively
      on both biologic models.

PMID- 9004436
TI  - The importance of rigorous testing of circumference measuring callipers.
AB  - On-screen circumference measurements are frequently made in obstetric ultrasound
      and are also made in other ultrasound specialties. The accuracy of electronic
      callipers is traditionally checked by linear measurement in a test object; this
      does not adequately test callipers used for nonlinear measurement. This technical
      note describes a simple test object designed for both linear and nonlinear
      calliper checks. Results show one machine to generate consistently large
      overmeasurements (15%). The clinical consequences of such overmeasurement may be
      serious. Appropriate quality control is essential.

PMID- 9004435
TI  - Finite amplitude distortion and its relationship to linear derating formulae for
      diagnostic ultrasound systems.
AB  - Formulation of indices that can be used as predictors of biological effects of
      ultrasound involves a process called derating, in which measurements of the sound
      field made in water are extrapolated to estimates of the magnitude of the sound
      fields in the tissues of the body. All indices that have been formulated up to
      the present time assume that the propagation of ultrasound is linear. In fact,
      under most exposure conditions for which biological effects may be a concern,
      sound propagation is highly nonlinear. A nonlinear propagation model has been
      used in this study to evaluate the nature of the effects that occur under
      realistic exposure conditions encountered in diagnostic procedures. Because of
      the way that the thermal index is defined, it turns out that ignoring nonlinear
      propagation leads to underestimates of tissue temperature increments that
      typically are less than 40%. As currently implemented, the mechanical index may
      be underestimated by more than a factor of two because it ignores the saturation
      of the sound fields that result from nonlinear propagation. For large propagation
      distances in soft tissues (e.g., 10 cm at 3 MHz in liver); however, it is
      physically difficult to exceed tissue pressures corresponding to MI > 2 because
      of these same saturation phenomena.

PMID- 9004437
TI  - Chances and risks of developing vaccines.

PMID- 9004438
TI  - Isotype-specific antibody responses to rotavirus and virus proteins in cows
      inoculated with subunit vaccines composed of recombinant SA11 rotavirus core-like
      particles (CLP) or virus-like particles (VLP).
AB  - The isotype antibody responses to bovine IND P5, G6 and simian SA11 P2, G3
      rotavirus and SA11 rotavirus proteins (VP4, VP6 and VP7) in serum, colostrum and
      milk were analysed by ELISA in three groups of vaccinated cows and nonvaccinated
      controls. Pregnant cows were vaccinated intramuscularly and intramammarily with
      recombinant baculovirus-expressed SA11 rotavirus VLP (triple-layered virus-like
      particles containing rotavirus VP2, VP4, VP6 and VP7); CLP (double-layered core
      like particles containing rotavirus VP2 and VP6); or inactivated SA11 rotavirus,
      respectively. Rotavirus antigen titers were highest (30-200-fold) in ELISA in the
      VLP vaccine compared to the inactivated SA11 vaccine. The IgG1, IgG2 and IgM
      geometric mean antibody titers (GMT) to rotavirus (titers to bovine rotavirus vs
      SA11 rotavirus did not differ significantly for any isotype or group) and the
      IgG2 GMT to VP6 in serum at calving in the vaccinated groups were significantly
      (P < 0.05) higher than in the control group. In colostrum, IgG1 and IgA rotavirus
      antibody titers were significantly elevated for VLP (IgG1 GMT 832225; IgA GMT
      16384), CLP (IgG1 GMT 660561; IgA GMT 10321) and SA11 (IgG1 GMT 131072; IgA GMT
      1448) vaccinated cows compared to control cows (IgG1 GMT 11585; IgA GMT 45). The
      IgG1 and IgA GMT to rotavirus were significantly elevated (6-100-fold) in milk of
      VLP and CLP vaccinated cows compared to SA11 vaccinated or control cows. The
      isotype antibody responses to VP6 in serum, colostrum and milk paralleled the
      responses to rotavirus, but titers were approximately 2-10-fold lower. Only cows
      vaccinated with VLP had significantly enhanced serum, colostral and milk antibody
      titers to rotavirus VP4 and VP7. These results demonstrate that rotavirus
      antibody titers in serum, colostrum and milk are significantly enhanced by use of
      non-infectious VLP, CLP and inactivated SA11 rotavirus vaccines, but the VLP or
      CLP vaccines induced the highest antibody responses, corresponding to their
      higher rotavirus antigen titers measured by ELISA.

PMID- 9004439
TI  - Application of murine T-T hybridoma cells to in vitro potency assay of human
      synthetic peptide vaccines.
AB  - Recently, it has been shown that the immunization of mice with an 18 amino acid
      synthetic peptide corresponding to the third hypervariable region of MHC class II
      beta chain can induce a specific antibody response against MHC class II
      molecules, and can be utilized in the prevention and treatment of experimental
      allergic encephalomyelitis (EAE) [Proc. Natl. Acad. Sci. 1994, 91, 8005-8009].
      Based on this finding, a chemically-modified synthetic peptide with the amino
      acid sequence corresponding to residues of beta 57-76 from human HLA-DR4Dw4
      (DR4/1 peptide) is being clinically investigated for the treatment of rheumatoid
      arthritis in human. The present study describes the development of a novel in
      vitro potency assay for human HLA-DR4/1 peptide using cloned murine T-T hybridoma
      cells. Several mouse strains were immunized with the DR4/1 peptide and their
      lymph node T cell proliferation was measured in the presence of syngeneic APCs
      and the DR4/1 peptide. T cells isolated from the peptide primed-B10. PL mouse
      strain, which showed the highest recall response in this assay, were fused with
      BW5147 lymphoma cells to generate DR4/1 peptide-specific T-T hybridoma clones.
      Cloned hybridoma cells were characterized for peptide specificity and MHC class
      II restriction, and used to monitor the biological activity of various DR4/1
      peptide preparations. The potency of peptide batches were assessed by measuring
      the IL-2 secretion of cloned T-T hybridoma cells upon TCR engagement in an
      antigen-specific manner. The quantitative detection of IL-2 was performed by
      measuring [3H]thymidine incorporation of HT-2 cells or directly by ELISA. These
      results demonstrate that peptide-specific murine T-T hybridoma clones can be
      successfully utilized to monitor biological activity of synthetic peptides by
      measuring T cell-mediated immunological responses. Development of such in vitro
      potency assay for synthetic peptides may have broad applications for vaccines
      related to immunological disorders.

PMID- 9004440
TI  - Romurtide, a synthetic muramyl dipeptide derivative, accelerates peripheral
      platelet recovery in nonhuman primate chemotherapy model.
AB  - We investigated the therapeutic effects of romurtide, a synthetic muramyl
      dipeptide derivative, on experimental thrombocytopenia induced by carboplatin in
      cynomolgus monkeys. A prolonged thrombocytopenia due to a severe myelosuppression
      was induced by carboplatin. Romurtide given subcutaneously elevated significantly
      the peripheral platelet counts during both early initiation and later recovery
      phase of thrombocytopenia, thereby shortening the time required for recovery to a
      normal platelet level and the duration of thrombocytopenia. An oral
      administration of romurtide was also found to have a similar therapeutic efficacy
      to subcutaneous administration. These results demonstrated a possible therapeutic
      potential of romurtide in the management of thrombocytopenia associated with
      myelosuppression.

PMID- 9004441
TI  - Adjuvancy and reactogenicity of N-acetylglucosaminyl-N-acetylmuramyl-dipeptide
      (GMDP) orally administered just prior to trivalent influenza subunit vaccine. A
      double-blind placebo-controlled study in nursing home residents.
AB  - One hundred and fifty-three nursing home residents received 0, 5, 25 or 50 mg N
      acetylglucosaminyl-N-acetylmuramyl-dipeptide (GMDP) orally, and trivalent
      influenza subunit vaccine intramuscularly. One day after intervention, there was
      a strong increase of total leucocytes, monocytes and neutrophils in the groups
      receiving 25 or 50 mg GMDP. A GMDP dose dependent increase in systemic, but not
      in local, vaccine side-effects was observed. No significant differences in post
      vaccination haemagglutination inhibiting serum antibody titres were observed
      between the four groups, indicating that oral administration of GMDP together
      with influenza vaccination, does not lead to a higher vaccine efficacy.

PMID- 9004442
TI  - Effects of repeated annual influenza vaccination on vaccine sero-response in
      young and elderly adults.
AB  - Three cohort studies in adults were performed during the period from 1986 to
      1989. Eight hundred and eighty-four subjects were, one or more times, immunized
      with influenza vaccines, and pre- and post-vaccination antibody titres were
      determined by hemagglutination inhibition tests. One thousand and one hundred and
      nineteen vaccination events in 681 subjects could be analysed by a comparison,
      per trial and per influenza (sub)type, between groups with and without influenza
      vaccination in previous years. Effect size, odds ratio and protection rate
      difference, were used as effect measures. Subjects with previous vaccination
      showed higher pre-vaccination antibody than those without. The average change of
      the post-vaccination proportion of subjects with high antibody titre value to
      previous vaccination, was +9.4% (95% CI: +5.3 to 13.6%) for A-H3N2 vaccine
      components, -2.1% (-8.1 to 3.9%, not significant) for A-H1N1 and -10.6% (-16.5%
      to -4.8%) for B. In a linear regression model, pre-vaccination titres and the
      status of previous vaccination were identified as factors significantly
      influencing post-vaccination titres. These findings are discussed in the context
      of a short review of the literature. It is concluded that the status of previous
      vaccination should always be addressed as an independent factor in serological
      vaccination studies.

PMID- 9004443
TI  - Antigenicity, cross-reactivity and surface exposure of the Neisseria meningitidis
      37 kDa protein (Fbp).
AB  - The 37 kDa iron-repressible protein, Fbp, was purified from two Neisseria
      meningitidis strains by metal-affinity chromatography and used to obtain mouse
      monospecific polyclonal immune sera. Dot-blot, immunoblotting and whole cell
      ELISA results demonstrate that the Fbp is present in all 16 N. meningitidis and
      four commensal Neisseria species tested, is highly antigenic in mouse when
      injected in pure form, and shows intra- and inter-species antigenic homogeneity,
      anti-Fbp antibodies being fully cross-reactive using the techniques mentioned. We
      also found that Fbp molecules (or parts of them) are surface exposed, in
      disagreement with the proposed exclusively periplasmic localization, although
      anti-Fbp antibodies seem unable to block iron uptake or to induce complement
      mediated killing of the meningococci. Taken along with the high immunogenicity of
      the purified protein and the complete cross-reactivity of the antibodies
      elicited, this suggests that the protective effect of the purified Fbp must be
      further studied to evaluate its inclusion in future vaccine trials.

PMID- 9004444
TI  - Vaccination of sheep against larvae of the sheep blowfly (Lucilia cuprina).
AB  - Four first stage larval antigens from the sheep blowfly were identified using
      supernatants from cultures of antibody secreting cells. These partially purified
      larval antigens, when added to Montanide ISA-25 containing recombinant ovine IL-1
      beta (rovIL-1 beta) were used to successfully vaccinate sheep against larvae of
      the sheep blowfly. Significantly less strikes were recorded on vaccinated sheep
      compared to controls (P < 0.033) with surviving larvae from vaccinated sheep up
      to 85% smaller than larvae from control sheep. RovIL-1 beta was found to be an
      important component of the vaccine. Vaccinated sheep showed both humoral and
      cellular immune responses to the larval antigens. Antibody levels generally
      correlated directly with delayed-type hypersensitivity (DTH) responses, but
      neither antibody nor DTH correlated positively with protection in vaccinated
      sheep. Skin sections removed from individual sheep immediately after challenge
      revealed aggregations of CD4+, gamma delta-TCR+ and CD1+ cells located directly
      under the epidermis in vaccinated sheep.

PMID- 9004446
TI  - Safety and immunogenicity of Lyssavac Berna human diploid cell rabies vaccine in
      healthy adults.
AB  - A clinical trial testing the safety and immunogenicity of a newly developed human
      diploid cell rabies vaccine (Lyssavac-HDC) was conducted on subjects at three
      colleges of veterinary medicine in the United States. Lyssavac-HDC is a sterile
      lyophilized vaccine containing no antibiotics or preservatives and is
      administered intramuscularly as a 0.5 ml dose of vaccine containing at least 2.5
      i.u. of rabies inactivated antigen per dose. Subjects were given either a three
      dose pre-exposure series (days 0, 7, and 28), followed by one booster dose of
      vaccine (day 360); or a five dose simulated post-exposure series of injections
      (days 0, 3, 7, 14, and 28). All subjects in the post-exposure and pre-exposure
      groups possessed adequate levels of rabies neutralizing antibody (> or = 5) when
      tested on day 14 and day 28, respectively. Subjects in the pre-exposure group
      demonstrated a vigorous anamnestic response after the administration of one
      booster dose of vaccine on day 360. The type and severity of local and systemic
      reactions observed were comparable to other primary cell culture rabies vaccines.
      Significantly, there were no type III hypersensitivity reactions reported in
      subjects previously immunized with Lyssavac-HDC after the administration of a
      booster dose of vaccine on day 360.

PMID- 9004445
TI  - A new family of carriers (biovectors) enhances the immunogenicity of rabies
      antigens.
AB  - Biovectors (BV) are a new family of protein carriers. They are nanoparticles of
      polymerized polysaccharides substituted with phosphate residues and surrounded by
      covalently bound lipid molecules (palmitic acid). The effect of BV was tested on
      the immunogenicity of rabies antigens. Biovectors enhanced the production of
      antibody induced by both rabies glycoprotein and ribonucleoprotein. Moreover,
      they enhanced the protective activity of an experimental rabies vaccine composed
      of inactivated and purified virus. The isotype profile of antibody produced in
      vivo was not modified when BV were mixed with rabies antigens. To clarify the
      mechanism of the adjuvant/ immunostimulation effect of BV, two types of approach
      were used: (1) analysis of the antibody response when antigen and BV were
      injected separately; (2) determination of the nature of cells involved in the
      proliferation in vitro of murine splenocytes in the presence of BV. The enhancing
      effect of BV on antibody production was highest when mixed with antigens. In
      vitro BV induced the proliferation of B cells. These findings suggest that BV
      have immunostimulating properties in addition to their probable depot and/or
      antigen-presentation effect which explain in part their adjuvant activity.

PMID- 9004447
TI  - Safety, efficacy, and immunogenicity of a recombinant Osp subunit canine Lyme
      disease vaccine.
AB  - A subunit canine Lyme disease vaccine formulated with recombinant lipidated Osp A
      and OspB and saponin QS21 was assessed for safety, protective efficacy, and
      immunogenicity. Ten normal beagles were subcutaneously vaccinated twice at age 12
      and 16 weeks, respectively. Three months after the second vaccination, the
      vaccinates and another 10 nonvaccinated control beagles were challenged by
      feeding ticks on each dog for 5 days using eight field-collected adult female and
      six adult male Ixodes scapularis infected with Lyme disease spirochetes per dog.
      Adverse reactions associated with the vaccinations were limited to injection site
      swellings which occurred within the first 48 h and resolved within a week. The
      local reaction was independent of vaccination times and tick challenge. On the
      basis of typical clinical signs, xenodiagnosis, and diagnostic immunoblotting,
      all 10 controls were infected; five developed lameness and three of them
      experienced at least two to three episodes of limping during a 10-month
      monitoring period. In contrast, eight of ten vaccinates were protected and two
      infected vaccinates, as judged by xenodiagnosis, were asymptomatic. None of the
      protected vaccinates developed antibodies to diagnostic spirochetal antigens
      other than OspA and OspB. In contrast, most controls produced antibodies to
      borrelial antigens, but not to OspA and OspB. Antibody production in vaccinates
      receiving a third vaccination 10 months postchallenge was greatly boosted; the
      geometric mean antibody titer was significantly higher (P < 0.0001) than that
      tested prechallenge. Thus, the subunit canine Lyme disease vaccine was safe and
      protective and elicited immunological memory. Vaccinated dogs were serologically
      distinguishable from those naturally exposed.

PMID- 9004449
TI  - A virosome vaccine antigen delivery system does not stimulate an antiphospholipid
      antibody response in humans.
AB  - A virosome vaccine delivery system comprised of the hemagglutinin of influenza A
      virus incorporated into unilamellar liposomes consisting of
      phosphatidylethanolamine (PE) and phosphatidylcholine (PC) or only PC was
      developed. The anti-PE and anti-PC antibody response was determined for human
      volunteers immunized with a virosome-formulated vaccine against hepatitis A, or a
      standard or virosome-formulated influenza vaccine. None of the 100 young adults
      who received two doses of the hepatitis A vaccine 1 year apart mounted a
      significant (greater than fourfold) antiphospholipid antibody response.
      Immunization with a single dose of trivalent influenza vaccine engendered a
      significant anti-PC and anti-PE antibody response in 1 of 32 elderly nursing home
      residents who received the virosome-formulated influenza vaccine and in 1 of the
      31 residents who received a commercial subunit vaccine. These findings indicate
      that the virosome system can potentiate the human immune response to vaccine
      antigens without a concomitant rise in antiphospholipid antibodies.

PMID- 9004448
TI  - Synthetic vaccine against foot-and-mouth disease based on a palmitoyl derivative
      of the VP1 protein 135-159 fragment of the A22 virus strain.
AB  - The peptide Palm2 135-159, a dipalmitoyl derivative of the 135-159 fragment of
      VP1 protein of the foot-and-mouth disease virus strain A22 was synthesized. In
      the experiments on mice, guinea pigs and sheep Palm2 135-159 possesses greater
      immunogenic and protective activity than the nonacylated 135-159 peptide. The
      synthetic vaccine against foot-and-mouth disease for use in sheep was developed
      on the basis of the lipopeptide. Synthetic polymethylsiloxane oil was found to be
      a suitable adjuvant for this vaccine. The dependencies of protective and
      immunogenic effects from the dose of peptide were studied. The vaccine was found
      to be stable to storage for 1 year at 18 degrees C. It was shown that the
      synthetic vaccine provides 1 year protection of sheep against foot-and-mouth
      disease after a single administration. The vaccine is allowed for veterinary use
      in Russia.

PMID- 9004450
TI  - Delivery of the Pertactin/P.69 polypeptide of Bordetella pertussis using an
      attenuated Salmonella typhimurium vaccine strain: expression levels and immune
      response.
AB  - Pertactin/P.69, a surface-associated polypeptide antigen of Bordetella pertussis,
      was expressed in a Salmonella typhimurium aroA aroD vaccine strain, BRD509, using
      different expression systems, and the immune response in mice against these
      constructs was compared. Initially, Pertactin/P.69 was expressed on the surface
      of BRD509 from a single copy of the gene encoding the antigen localized on the
      Salmonella chromosome. As previously shown, secretory and humoral antibody
      responses could not be detected following multiple immunization with this strain
      (BRD640). However, a strong anti-Pertactin/P.69 proliferative response was
      observed in murine splenocytes following a single oral dose with BRD640. The
      stimulated splenocytes secreted interferon-gamma but not interleukin-5,
      indicating that BRD640 induced a Th1 type T-helper response against
      Pertactin/P.69. We wished to construct a vaccine strain that might induce
      secretory and humoral responses against Pertactin/P.69 as well as a cell-mediated
      immune response. Consequently, Pertactin/P.69 was expressed at high levels in the
      cytoplasm of BRD509 under the control of the inducible nirB promoter from a ColE1
      based replicon. Anti-Pertactin/P.69 immune responses were not observed following
      immunization of BALB/c mice with this strain (BRD975). Priming of the immune
      system against Pertactin/P.69 was, however, observed following oral immunization
      with BRD975 and boosting subcutaneously with purified Pertactin/P.69 antigen. The
      major anti-Pertactin/P.69 IgG subclass detected in boosted mice was IgG2a; thus,
      as BRD640, BRD975 appeared to induce a Th1 type T-helper response against
      Pertactin/P.69.

PMID- 9004452
TI  - Biotransformation and detoxification of insecticidal metyrapone analogues by
      carbonyl reduction in the human liver.
AB  - 1. The carbonyl reduction of insecticidal metyrapone analogues to their hydroxyl
      metabolites by human liver microsomes and cytosol was examined. Metabolite
      quantification was performed by means of hplc determination and inhibition
      experiments, using specific carbonyl reductase inhibitors, were conducted. 2. The
      cytotoxicity of the ketones and their hydroxy metabolites was assessed with the
      MTT test, using Chang liver cells. 3. It was found that the alcohol derivatives
      are the major metabolite, both in microsomes and cytosol. The microsomal
      reductive metabolism, considered to be mediated by 11 beta-hydroxysteroid
      dehydrogenase (11 beta-HSD) (EC 1.1.1.146), was more extensive than the cytosolic
      carbonyl reduction. In each case, this metabolism was inhibited significantly by
      equimolar concentrations of the microsomal 11 beta-HSD inhibitor glycyrrhetinic
      acid and the cytosolic carbonyl reductase inhibitor quercitrin, respectively. 4.
      The parent ketones were more cytotoxic than their alcohol metabolites. 5. These
      results demonstrate that the metyrapone analogues are extensively metabolized by
      human liver microsomes, presumably by 11 beta-HSD, to the less cytotoxic and
      readily excretable alcohols. 6. Since the metyrapone analogues can inhibit
      ecdysone 20-monooxygenase (EC 1.14.99.22), our results indicate potential
      application of these compounds as insecticides, which would be safer for humans,
      due to their reductive detoxification, mainly by the hepatic microsomal 11 beta
      HSD, to the less toxic hydroxy metabolites.

PMID- 9004454
TI  - Dietary modulation of human platelet phenolsulphotransferase activity.
AB  - 1. The mammalian phenolsulphotransferase enzymes are known to play a major role
      in both the detoxification and possibly the activation of pre-carcinogenic
      phenols and aromatic amines. 2. Vegetable cytosol preparations were tested in
      vitro for their ability to affect the sulphation of two reference compounds (rho
      nitrophenol and dopamine, which are selective substrates for the phenol and
      monoamine forms of phenolsulphotransferase respectively), and to act as
      substrates for the enzymes in comparison with the same reference compounds. 3.
      The majority of cytosols greatly decreased (> 80%) the sulphation of either or
      both the reference compounds. This effect may have been due to either enzyme
      inhibition or substrate binding. 4. Whereas some of the cytosols were sulphated
      under the assay conditions, most were not. Additionally, it was found that a
      cytosol that decreased the sulphation of the two reference compounds was not
      necessarily poorly sulphated itself. 5. It is concluded that dietary factors have
      the potential to play a major role in modulating the sulphation detoxification
      pathway, and have wide ranging implications with regard to adverse drug
      reactions.

PMID- 9004453
TI  - Inhibition of tolbutamide 4-methylhydroxylation by a series of non-steroidal anti
      inflammatory drugs in V79-NH cells expressing human cytochrome P4502C10.
AB  - 1. To study the role of cytochrome P4502C10 in the metabolism of the non
      steroidal antiinflammatory drugs (NSAIDs) diclofenac, phenylbutazone, fenoprofen,
      ibuprofen, flurbiprofen, ketoprofen and naproxen, a cell line was developed
      stably expressing CYP2C10 cDNA. A retroviral vector construct, containing a human
      CYP2C10 cDNA, was transfected in V79-NH Chinese hamster lung cells by calcium
      phosphate co-precipitation. Sublines stably expressing human cytochrome P450 cDNA
      were established by selection with the neomycin analogue G418. 2. Enzymatic
      activity of CYP2C10 was detected by 4-methylhydroxylation of tolbutamide. This
      activity was inhibited to background levels by preincubation with the CYP2C9/10
      inhibitor sulphaphenazole. 3. Preincubations with the NSAIDs ketoprofen,
      phenylbutazone, flurbiprofen and diclofenac (all 250 microM) caused a decrease in
      4-methylhydroxylation of tolbutamide (500 microM), significantly different from
      control values (p < 0.05). Inhibition of this activity was not seen in
      preincubations with the NSAIDs fenoprofen, ibuprofen and naproxen (250 microM).
      4. The V79-NH CYP2C10 cell line we have developed has been shown to be a useful
      tool to predict drug-drug interactions.

PMID- 9004455
TI  - (S)-4'-hydroxypropranolol causes product inhibition and dose-dependent
      bioavailability of propranolol enantiomers in the isolated perfused rat liver and
      in rat liver microsomes.
AB  - 1. Previous evidence suggests that the dose-dependent bioavailability of racemic
      propranolol may be partly due to product inhibition. We have examined this
      further by studying the individual enantiomers of propranolol in the perfused rat
      liver (IPRL) and in rat liver microsomes. 2. In recirculating IPRL experiments,
      (R)-propranolol (n = 7) or (S)-propranolol (n = 4) were infused at rates of 75,
      150 and 231 nmol/min for three sequential 36-min phases. In single-pass
      experiments, (R)-propranolol (n = 4) or (S)-propranolol (n = 4) were administered
      at rates of 80, 136 and 239 nmol/min for three sequential 30-min phases. Steady
      state bioavailability increased 10-20-fold over this dose range with both
      enantiomers in both recirculating and single-pass experiments. At the higher
      administration rates of (S)-propranolol, bioavailability in recirculating
      experiments was significantly greater than that in single-pass experiments,
      whereas there was no significant difference for (R)-propranolol. This suggests
      product inhibition of (S)- but not (R)-propranolol metabolism. 3. Of the
      metabolites examined, racemic 4'-hydroxypropranolol (4-OHP) inhibited the
      formation of 4-OHP, 5'-hydroxypropranolol (5-OHP) and desisopropylpropranolol
      (DIP) from (S)-propranolol and (R)-propranolol in microsomal studies (IC50 20
      microM). Tissue levels of (S)-4-OHP in recirculating experiments (28.0 microM) at
      the highest dose (239 nmol/ min) of (S)-propranolol were greater than its IC50 of
      20 microM, suggesting that 4-OHP is the inhibiting metabolite in the intact
      liver. The absence of evidence for product inhibition with (R)-propranolol in
      perfused livers suggests that (S)-4-OHP inhibits 4-hydroxylation of each isomer
      but (R)-4-OHP does not. 4. We conclude that in the recirculating IPRL, product
      inhibition of propranolol metabolism is evident with the (S)-isomer, but not he
      (R)-isomer, and that the inhibiting metabolite is (S)-4-OHP.

PMID- 9004456
TI  - Biotransformation of diethenylbenzenes, V. Identification of urinary metabolites
      of 1,2-diethenylbenzene in the rat.
AB  - 1. Biotransformation of 1,2-diethenylbenzene (1) in rat was studied. Five urinary
      metabolites were isolated by extraction of acid hydrolysed urine and identified
      by nmr and mass spectroscopy, namely, 1-(2-ethenylphenyl)ethane-1,2-diol (2) 2
      ethenylmandelic acid (3), 2-ethenylphenylglyoxylic acid (4), 2
      ethenylphenylacetylglycine (5) N-acetyl-S-[1-(2-ethenylphenyl)-2
      hydroxyethyl]cysteine (6) and N-acetyl-S-[2-(2-ethenylphenyl)-2-hydroxy
      ethyl]cysteine (7). 2. In addition, minor metabolites, namely, 2-ethenylbenzoic
      acid (8) and 2-ethenylphenyl-acetic acid (9) were identified by glc-mass spectral
      analysis of the hydrolysed urine extract treated subsequently with diazomethane,
      hydroxylamine and a trimethyl-silylating reagent. Several compounds, which could
      arise from biotransformation of both ethenyl groups in the molecule of 1, were
      detected but not identified unequivocally. 3. A glucuronide was detected by tlc
      analysis of urine as a blue spot after spraying with naphthoresorcinol. Compounds
      showing molecular fragments indicating the glucuronide moiety were also detected
      by glc-mass spectroscopy in non-hydrolysed urine samples. 4. The total thioether
      excretion amounted to 5.3 +/- 2.4, 5.1 +/- 3.4 and 5.0 +/- 1.9% of the dose at
      500, 300 and 100 mg/kg, respectively (mean +/- SD; n = 5). 5. Like styrene and
      other diethenylbenzene isomers, 1,2-diethenylbenzene is metabolically activated
      to a reactive epoxide intermediate, 2-ethenylphenyloxirane (10), which is further
      converted to the urinary metabolites mentioned above. The main detoxification
      pathways are hydrolysis to the glycol 2 followed by several oxidation steps, and
      conjugation with glutathione. The latter reaction is both regioselective and
      stereoselective. 6. The ratio of mercapturic acids 6:7 was 83:17. Each
      regioisomer consists of two diastereomers which show distinct resonance signals
      in the 13C-nmr. The diastereomer ratio was 82:28 and 79:21 for 6 and 7
      respectively.

PMID- 9004457
TI  - Absorption, pharmacokinetics and metabolism of 14C-sumatriptan following
      intranasal administration to the rat.
AB  - 1. Studies have been carried out to investigate the absorption of sumatriptan
      after intranasal administration to rats. The pharmacokinetics, metabolism and
      excretion of 14C-sumatriptan were compared following intranasal and intravenous
      dosing to male and female albino rats using an aqueous buffered formulation at pH
      5.5. 2. Following intravenous administration sumatriptan was eliminated from
      plasma with a half-life of about 1.1 h. After intranasal administration there was
      rapid absorption of part of the dose and two peak plasma concentrations were
      observed, initially at 0.5 and then at 1.5-2 h. The elimination half-life after
      the second peak was estimated as being about 4 h. 3. Radioactivity was largely
      excreted in urine (up to 89% of dose in 168 h) after both intravenous and
      intranasal administration, with a faster rate of excretion after intravenous
      dosage (73% males, 64% females within 6 h) than after intranasal dosage (37%
      males, 40% females within 6 h). 4. 14C-sumatriptan was the major component in
      urine and in extracts of faeces after both intravenous and intranasal
      administration. The major metabolite excreted in urine and faeces was GR49336,
      the indole acetic acid analogue. 5. The results of this in vivo rat study suggest
      that absorption of the dose via the nasal mucosa is incomplete after intranasal
      administration and that there is a secondary absorption phase probably reflecting
      oral absorption of part of the dose. The bioavailability is estimated as about
      30%, for the period 0-6 h.

PMID- 9004458
TI  - Effects of fenthion, isoxathion, dichlorvos and propaphos on the serum
      cholinesterase isoenzyme patterns of dogs.
AB  - The serum cholinesterase (ChE) isoenzyme patterns consist of 5 bands for normal
      beagle dogs. We examined the ChE isoenzyme patterns and ChE activities of 4
      groups, each of which consisted of 4 dogs, given the organophosphate (OP)
      compounds fenthion (P = S type), isoxathion (P = S type), dichlorvos (P = O type)
      or propaphos (P = O type) po at 220, 75, 120 or 90 mg/kg respectively. Blood
      samples were collected for 30 d after the OP administrations. ChE isoenzyme bands
      4 and 5 were inhibited 12 h after fenthion and isoxathion administration;
      dichlorvos and propaphos produced suppression of main bands 4 and 5 20 min after
      administration. This change was effective to differentiate the type of OP
      administered (P = S and P = O), while the main ChE isoenzyme bands of dog serum
      reflected inhibition of serum ChE activity.

PMID- 9004459
TI  - Erythrocyte glutathione-S-transferase activity in animal species.
AB  - This study was conducted to determine and compare the activities of glutathione-S
      transferase (GST) in red blood cells of cattle, horses, pigs, goats, dogs,
      rabbits, rats and mice. The highest GST activity was found in mouse red blood
      cells followed by that of rats, dogs, cattle, pigs, goats and horses with the
      lowest activity in rabbits. There were significant differences between the GST
      activities from these various species. The species differences in GST activities
      correlate with the reported variable responses of the different species to
      different toxicants since erythrocyte GST plays a significant role in the
      detoxification of circulating xenobiotics.

PMID- 9004460
TI  - Comparative kinetic analysis of cholinesterase methods in rat and human
      erythrocytes and plasma.
AB  - A kinetic analysis of the substitution of 6,6'-dithiodinicotinic acid (DTNA) for
      5,5'-dithiobis-2-nitrobenzoic acid (DTNB) for the determination of rat and human
      erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7) and plasma
      butyrylcholinesterase (BuChE; EC 3.1.1.8) is presented. Increasing concentrations
      of DTNB, but not DTNA, significantly increased Km for the substrate
      acetylthiocholine but had little or no effect on Vmax for rat or human AChE. The
      coupling agent DTNA was more efficient than DTNB, as demonstrated by the higher
      Vmax/Km ratio for the former. DTNB, more so than DTNA, caused linear mixed-type
      inhibition of rat AChE. Poor precision was observed for the DTNB versus DTNA
      method. Reagent blanks were a significant component of rat, but not human, AChE
      activity. The use of DTNA in place of DTNB is recommended for quantitative
      mechanistic investigations of cholinesterases. The most practical aspect of the
      DTNA method is that it can be adapted to automated instruments which can monitor
      the change in absorbance at 340 nm, away from the hemoglobin peak.

PMID- 9004461
TI  - Effect of vitamin A supplementation on cigarette smoke-induced lipid
      peroxidation.
AB  - The antioxidant activity of vitamin A against cigarette smoke-induced oxidative
      stress was investigated in rat tissues. The rats were exposed to cigarette smoke
      for 90 d and simultaneously given 5,000 IU vitamin A/kg body weight. Lipid
      peroxidation products, scavenging enzymes and free fatty acids were estimated in
      liver, lungs and heart. Cigarette smoke exposure increased the concentrations of
      malondialdehyde, conjugated dienes and hydroperoxides. The activities of
      superoxide dismutase and catalase were decreased, but glutathione content and
      glutathione peroxidase (GSSG-Pxase) activity were enhanced. Glutathione reductase
      (GSSG-Rase) activity was markedly inhibited. Vitamin A supplementation to smoke
      exposed rats produced increased resistance to lipid peroxidation and increased
      the activities of scavenging enzymes, producing normal or higher enzyme
      activities. The activities of GSSG-Rase and GSSG-Pxase and the glutathione
      content reduced to normal levels. These results indicate that lipid peroxidation
      induced by cigarette smoke can be protected against by vitamin A supplementation
      and their protection may be due to vitamin A's antioxidant activities.

PMID- 9004462
TI  - Prevention and treatment of dichlorvos-induced toxicosis in mice by
      diphenhydramine.
AB  - Dosing male mice with 125 mg dichlorvos/kg orally produced cholinergic
      overstimulation and death in up to 100% of the animals. Administration of 20 or
      30 mg diphenhydramine HCl/kg s.c. 15 min before dichlorvos dosing significantly
      reduced the development of toxicity and increased 24-h survival rates to 87 and
      100% respectively. Diphenhydramine was less effective when given immediately
      after dichlorvos dosing; however, repetitive treatments of 20 mg
      diphenhydramine/kg s.c. increased the survival rate to 75%. The administration of
      a single injection of 30 mg diphenhydramine/kg s.c. 15 min before dichlorvos
      dosing or as multiple s.c. or i.p. doses after dichlorvos increased the 24-h oral
      dichlorvos LD50 by 30, 50 or 70%, respectively. The anticholinergic effects of
      diphenhydramine protects and effectively treats mice poisoned with dichlorvos.

PMID- 9004463
TI  - Intravenous 4-methylpyrazole as an antidote for diethylene glycol and triethylene
      glycol poisoning: a case report.
AB  - Diethylene glycol (DEG) intoxication resembles that of ethylene glycol, with
      progressive inebriation, anion gap metabolic acidosis, renal failure, coma and
      death. DEG is oxidized by alcohol dehydrogenase (ADH) to more toxic byproducts,
      thus blockade of ADH might be beneficial. Triethylene glycol (TEG), also
      metabolized by ADH, is less toxic. A young female suicidally ingested DEG and
      TEG, presenting in metabolic acidosis with coma. Given 4-methylpyrazole (4-MP),
      an ADH inhibitor, the acidosis resolved, the patient recovered and was discharged
      without sequelae. 4-MP, if supported by further studies, may be useful in DEG
      poisoning.

PMID- 9004464
TI  - Acute toxicosis in cattle sprayed with endosulfan.
AB  - Two cattle died acutely after being sprayed for lice control with a cyclodiene
      organochlorine insecticide, endosulfan, not labelled for use in cattle. Three
      other cattle became acutely ill, but survived after symptomatic therapy and
      removal of the insecticide from their skin and prevention of enterohepatic
      circulation. These cases illustrated the risk of acute toxicosis when
      organochlorine insecticides are used off-label and the potential for illegal
      tissue and milk residues.

PMID- 9004465
TI  - Death following intentional methyl bromide poisoning: toxicological data and
      literature review.
AB  - A case of fatal poisoning due to ingestion-inhalation of methyl bromide (MeBr) is
      presented. In previously reported fatalities due to MeBr inhalation, only
      inorganic bromide levels in biological specimens were reported. Intact MeBr has
      not been isolated from human tissues following exposure. In the present case,
      MeBr was detected, confirmed and quantitated in various biological samples by
      headspace gas chromatography, and the clinical manifestations and autopsy
      findings are described. Postmortem MeBr peripheral blood concentration was 3.3
      micrograms/mL and in subclavian blood was 3.8 micrograms/mL. Lung, brain, adrenal
      gland, kidney, liver and testis MeBr was 2.9, 3.5, 3.4, 2.6, 1.9 and 2.8
      micrograms/g respectively; MeBr in bile was 1.2 micrograms/mL. Inorganic bromide
      concentrations were 530, 30, 310 and 130 micrograms/g in blood, brain, kidney and
      adrenal gland respectively.

PMID- 9004466
TI  - Fatal animal poisonings in northern Greece: 1990-1995.
AB  - Fatal animal poisonings in northern Greece from 1990 to 1995 are recorded. A
      total of 926 specimens have been analyzed by chromatographic techniques.
      Pesticides caused 78% of the poisoning cases and all other toxic substances
      caused 22%. The animals affected were mainly cats, dogs, sheep, birds and bees.

PMID- 9004467
TI  - Immunoprophylactic intervention in chemical toxicity and carcinogenicity.
AB  - Preventing or diminishing the effects of environmental carcinogens and toxicants
      using immunoprophylactic vaccines has been tested by various investigators for
      the last 60 y. This approach has not gained widespread interest in scientific or
      medical communities due to ambiguous results. However, advances in vaccine design
      and immunization protocols now offer a reliable mechanism for the induction of
      mucosal immunity which may afford protection from these agents at their site of
      absorption. Previous studies aimed at immunoprophylactic vaccination against
      carcinogens and toxicants are reviewed, and future directions for this area of
      research are discussed.

PMID- 9004468
TI  - Effectiveness of a poison center: impact on medical facility visits.
AB  - To estimate the effectiveness of a poison center by determining the number of
      potential medical facility visits for childhood poisonings which are prevented,
      and to determine how callers learned about the poison center in order to help
      guide future public educational efforts, a cross-sectional telephone survey was
      done. A systematic sample of caretakers of children < 6-y-of-age living in Harris
      County, TX, and who called the poison center about a poisoning incident between
      February 1993 and January 1994, was taken. One hundred sixty-six/197 eligible
      caretakers (84%) completed the survey. Of the 166 caretakers, only 5 (3%) were
      referred by the poison center to a medical facility for treatment, although 6
      (3.6%) actually sought medical attention. The remaining 160 (96.4%) were
      successfully managed at home. The majority of these (74%) required no
      intervention and the remaining 26% required only minimal treatment, including
      ipecac, dilution, irrigation or observation. Of the 160 caretakers managed at
      home, 69 (43%) would have sought medical attention for the child at a health care
      facility if the poison center did not exist, and of those 81% would have gone to
      an emergency center or hospital for evaluation. Callers learned about the poison
      center most often from family/ friends, doctors, Mr Yuk stickers, television,
      previous use, or pharmacists. Poison centers decrease health care costs by
      preventing unnecessary medical facility visits for minor childhood poisonings
      which can be successfully managed at home. Methods effective in educating the
      public about poison centers should be continued and other methods explored to
      increase poison centers' use.

PMID- 9004469
TI  - Effect of a German Poison Control Center on health care cost reductions in
      harmless exposure cases.
AB  - To evaluate the effect of a German Poison Control Center (PCC) service on health
      care cost reduction in cases of harmless exposures, a prospective telephone
      survey of 200 callers were asked which medical aid would have been sought if no
      PCC service had been available. Calculation of savings was based on the total
      number of calls and standardized fees for medical treatment. Savings in costs for
      health insurance in these cases was 20 to 50% of the annual PCC budget. The cost
      effectiveness of this German PCC for this patient group was lower than for North
      American PCCs. Cost effectiveness might be improved by making efforts to increase
      the number of public calls.

PMID- 9004470
TI  - Experiences of a new poison specialist.

PMID- 9004471
TI  - Pyrethroid residues in milk and blood of dairy cows following single topical
      applications.
AB  - The presence of the pyrethroid insecticides flumethrin, deltamethrin,
      cypermethrin and cyhalothrin in milk and blood of 10 cows was determined after
      single dermal applications of recommended doses. Milk and blood samples were
      collected every 7 days over a 35-d period and analyzed by high-performance liquid
      chromatography. The highest residues in milk were found on day 28 for flumethrin
      and day 1 for deltamethrin, cypermethrin and cyhalothrin, while in blood the
      highest concentrations were present on day 28 for flumethrin and deltamethrin,
      the first day for cypermethrin, and day 14 for cyhalothrin.

PMID- 9004472
TI  - Government announces proposals for a certified herds scheme...

PMID- 9004473
TI  - MAFF sets out its proposals for the selective cattle cull.

PMID- 9004475
TI  - Isolation of the causative agent of heartwater (Cowdria ruminantium) from three
      Amblyomma species in eight Districts of Kenya.
AB  - Thirteen isolates of Cowdria ruminantium were made from eight different Districts
      of Kenya by four different isolation methods. Feeding adult Amblyomma species
      ticks derived from nymphs collected in the field and the inoculation of
      homogenates prepared from adult field ticks had the highest success rate. The
      reattachment of adult ticks collected in the field was successful on only one of
      five attempts, and the subinoculation of blood from suspected heartwater carriers
      was unsuccessful. Seven of the isolates were derived from A variegatum ticks,
      four from A gemma, one from A lepidum and one from a mixed pool of the last two
      species. This is the first report of the isolation of C ruminantium from A gemma
      ticks, and the first report of its transtadial transmission from nymphal to adult
      A gemma.

PMID- 9004474
TI  - Effects of the duration of lairage following transportation on the behaviour and
      physiology of farmed red deer.
AB  - Eight groups of five farmed red deer were transported by road for three hours,
      after which they were either slaughtered immediately (TO) or held in lairage for
      three, six or 18 hours (T3, T6 and T18). Liveweight loss increased with lairage
      time but hot carcase weight was unaffected. Deer spent much of the initial period
      in lairage standing stationary in 'alert' postures. After eight to 10 hours the
      proportions of time spent in various postures (standing stationary, moving and
      lying down) were similar to pre-journey values. None of the blood components
      associated with dehydration (packed cell volume, osmolality, total protein and
      sodium) changed significantly with lairage time. Compared with T0 deer, plasma
      creatine kinase activity was significantly decreased in T18 deer. Lairage time
      had no effect on skin damage, bruising or muscle glycogen content, although liver
      glycogen content increased with longer lairage time. Although lairage time had a
      statistically significant effect on muscle pHu (with T6 deer having the lowest
      values), the differences were small and none of the carcases had a pHu greater
      than 6-0.

PMID- 9004476
TI  - Antithrombin-III activity in plasma of healthy and sick cattle.
AB  - Antithrombin-III (AT-III) activity was determined in the plasma of 32 healthy
      cows. The range of activities was between 105 and 160 per cent of a human
      reference plasma; the median activity was 132.5 per cent, and the 5 per cent and
      the 95 per cent quartiles were 111.1 per cent and 153.9 per cent of the standard.
      The activity of AT-III was also determined in 82 cows with a variety of internal
      diseases. In cows with hepatopathy, acute enteritis, generalised peritonitis,
      blood loss, idiopathic cardiomyopathy, glomerulonephritis and disseminated
      coagulopathy, the activity of AT-III was lower than in healthy animals. The lower
      values were due to decreased synthesis, increased consumption, or the loss of AT
      III. An acquired deficiency of AT-III appears to favour the development of
      thrombophlebitis.

PMID- 9004477
TI  - Effect of Leptospira interrogans serovar hardjo infection on progesterone
      concentrations in heifers.

PMID- 9004478
TI  - Newcastle disease outbreak in pheasants in Great Britain in May 1996.

PMID- 9004479
TI  - Nasal infection with Pasteurella multocida causes proliferation of bladder
      epithelium in gnotobiotic pigs.

PMID- 9004480
TI  - Veterinary education.

PMID- 9004481
TI  - Veterinary education.

PMID- 9004482
TI  - Mange in domesticated rats.

PMID- 9004483
TI  - Towards an understanding of the structural and functional properties of MscL, a
      mechanosensitive channel in bacteria.
AB  - Whether it be to sense a touch, arterial pressure, or an osmotic gradient across
      a cell membrane, essentially all living organisms require the capability of
      detecting mechanical force. Electrophysiological evidence has suggested that
      mechanosensitive ion channels play a major role in many systems where mechanical
      force is detected. But, despite their biological importance, determination of the
      most basic structural and functional features of mechanosensitive channels has
      only recently become possible. A gene called mscL, which was isolated from
      Escherichia coli, was the first gene shown to encode a mechanosensitive channel
      activity. This channel directly responds to tension in the membrane; no other
      proteins are required. MscL appears to be a homohexamer of a 136 amino acid
      polypeptide that is highly alpha helical, contains two transmembrane domains, and
      has both the amino and carboxyl termini in the cytoplasm. The study of the MscL
      protein remains, to date, one of the most viable options for understanding the
      structural and functional characteristics of a mechanosensitive channel.

PMID- 9004484
TI  - Nuclear and cytoplasmic actin in dinoflagellates.
AB  - Experiments using monoclonal and polyclonal anti-actin antibodies allowed us to
      demonstrate the presence of F- or G-actin in original protists, dinoflagellates,
      either by biochemistry, immunofluorescence and in TEM. SDS-PAGE electrophoresis
      and immunoblottings made either from total or nuclear protein extracts revealed
      the presence of a 44-kDa band reacting with monoclonal anti-actin antibody in two
      species, Prorocentrum micans and Crypthecodinium cohnii, and thus demonstrated
      the presence of actin in nuclear and cytoplasmic fractions. After squash
      preparation of P micans cells, actin was identified within the nucleus and in
      some regions of the cytoplasm by immunofluorescence microscopy. Labelling of both
      the nucleolus and the centrosome region was evident together with amorphous
      nucleoplasmic material surrounding the chromosomes. The use of cryosections of
      intact P micans and C cohnii cells for immunofluorescence along with staining
      with DAPI to delineate the chromosomes themselves, yielded finer resolution of
      the intranuclear network labelling pattern and allowed us to complete our
      observations, in particular on the cytoplasmic labelling. In P micans, in
      addition to the centrosome region, the cytoplasmic channels passing through the
      nucleus in dividing cells are labelled. In C cohnii, the cortex, the centrosome
      region, the cytoplasmic channels, the region surrounding the nucleus, the
      filaments linking it to the cortex and the cleavage furrow are also labelled. In
      the nucleus of the two species, there is a prominent "weft' of fine actin
      filaments in the nucleoplasm forming a matrix of varying density around the
      persistent chromosomes. This actin matrix, of unknown function, is most
      conspicuous at the end of the S-phase of the cell cycle. Fluorescent derivatives
      of phalloidin, used as diagnostic cytochemical probes for polymeric actin (F
      actin), gave similar results. Positive TEM immunolabelling of intranuclear actin
      confirms its presence in the nucleoplasm, in the nucleolus where the preribosomal
      region is labelled while C cohnii chromosomes are unlabelled and the P micans
      chromosomes very slightly. In the cytoplasm, lips of the cleavage furrow and
      kinetosome regions are labelled as well as the centrosome region. The possible
      functions of this protein located in several compartments of dinoflagellate cells
      are discussed.

PMID- 9004485
TI  - Internalization of oligodeoxynucleotide antisense to type-1 plasminogen activator
      inhibitor mRNA in endothelial cells: a three-dimensional reconstruction by
      confocal microscopy.
AB  - A three-dimensional reconstruction analysis of localization of phosphodiester and
      phosphorothioate oligonucleotide antisense to type-1 plasminogen activator
      inhibitor (PAI-1) mRNA within endothelial cells is described. When EA.hy 926
      cells were incubated with fluorescently labelled phosphodiester (PO-16) or
      phosphorothioate (PS-16) oligonucleotides at low, not cytotoxical concentrations,
      the relative brightness composition of the images of the particular samples was
      much higher for PS-16 than PO-16 and dependent upon the extracellular
      concentration and the incubation time. The 3-D reconstructions based on the
      series of optical sections of the samples, spaced every 1.5 microns, showed the
      punctuate accumulation of the oligonucleotides and a striking difference in a
      spatial distribution between PO-16 and PS-16 within the cytoplasm. Even after 24
      h incubation of endothelial cells with 2.5 microM of PO-16 and PS-16
      oligonucleotides, there was a predominant oligonucleotide localization within the
      cytoplasm and only traces of oligonucleotides could be seen in the cell nucleus
      and/or perinuclear organelles.

PMID- 9004486
TI  - A mutation (dosach) in Drosophila which affects aster formation and nuclear
      migration during cleavage.
AB  - Here we describe a new mutant, dosach (dos), in Drosophila melanogaster. In the
      mutant, centrosomes divide and initiate spindle formation similar to that seen in
      wild-type embryos. Nevertheless, mutant embryos form cleavage spindles that lack
      visible asters and display abnormal morphology, including mono- and tri-polar
      spindles, spindle chains and incorrect alignment. Irregular nuclear migration is
      also observed in mutant embryos, and this may suggest that astral microtubules
      are important for spindle spacing during cleavage and also in maintaining the
      integrity of the mitotic apparatus. Confocal microscopy has been used to
      correlate organization of microtubules, centrosomal proteins and chromosomes in
      wild-type and dosach (dos) embryos.

PMID- 9004487
TI  - Selective distribution of multiple protein kinase C isoforms in mouse cerebellar
      cortex.
AB  - An immunohistochemical study concerning the distribution of protein kinase C
      isoforms, a lipid-regulated serine/threonine kinase essential for signal
      transduction, was performed in mice cerebellar cortex, with particular emphasis
      on the localization of -iota and -lambda isozymes. By the means of immunoblotting
      analyses we detected the presence of 11 PKC subspecies in whole cerebellar
      extracts. Immunoreactivity on cryostat sections revealed, using polyclonal and
      monoclonal antibodies, that a few isoforms were widely but discretely distributed
      in all three cortical layers (molecular, granular and Purkinje cells) whereas
      other isozymes were present in a limited neuronal compartment. Overall, the
      distribution of several isoforms was in agreement with data obtained by other
      authors using rat cerebellum. As far as -iota and -lambda isozymes were
      concerned, we found them abundantly expressed in endothelial cells. Moreover,
      protein kinase C-lambda was also present in the body of Purkinje cell,
      conceivably associated with a 200-kDa neurofilament component. In all, these
      results hint at the possibility that in the cerebellar cortex at least some
      protein kinase C isoforms are involved in functions other than signal
      transduction at the synaptic level.

PMID- 9004488
TI  - Glial fibrillary acidic protein as a marker of perisinusoidal stellate cells that
      can distinguish between the normal and myofibroblast-like phenotypes.
AB  - Glial fibrillary acidic protein (GFAP) has recently been shown to provide a
      marker for normal perisinusoidal stellate cells (PSC) in the liver. However,
      nothing was known so far about the changes in the intercellular abundancy of GFAP
      during transformation of PSC into myofibroblasts, a process characterized by
      marked changes in the expression of elements of the cytoskeleton. In order to
      address this question, we have used double-labelling immunofluorescence
      techniques for detecting smooth muscle alpha-actin (SMAA) and the intermediate
      filament proteins, GFAP, desmin and vimentin, taking advantage of the fact that
      PSC present in primary cultures of rat hepatocytes proliferate and transform.
      GFAP and vimentin were expressed in PSC throughout cultivation, while desmin
      which stained only about half of the PSC in early cultures was expressed in all
      GFAP-positive cells later on. The intensity of staining for GFAP in PSC
      transiently increased till the second day of cultivation followed by a decrease.
      At the 6th day of cultivation, staining for GFAP was seen only in the perinuclear
      region and as a faint rim at the contours of the cells. In contrast, SMAA, an
      established marker for transformed PSC, started to be expressed at the third day.
      Thereafter, immunoreactivity for SMAA increased continuously, indicating an
      inverse expression of GFAP and SMAA during transformation. These results indicate
      that GFAP, due to the plasticity of its expression, can discriminate between the
      normal untransformed and transformed phenotypes of PSC. Furthermore, they suggest
      a role of GFAP not only as a reliable marker, but also in the maintenance and/or
      function of the normal differentiated phenotype of liver PSC.

PMID- 9004489
TI  - Uptake and release of 2-aminoisobutyrate by Leishmania donovani: culture-age
      dependent effects of osmolality and of protein kinase inhibitors.
AB  - The rate of uptake of 2-aminoisobutyrate (AIB), a non-metabolizable analogue of
      alanine, by Leishmania donovani was investigated as a function of culture age and
      osmolality in the presence of protein kinase inhibitors and of glucose, glutamate
      or proline. Hyperosmolality inhibited AIB uptake by cells of both growth stages,
      but to a greater extent for log than for stationary cells. Staurosporine, a
      protein kinase C inhibitor, had no effect on AIB uptake by cells of either
      culture age, but it reduced the rate of AIB release in response to hypo
      osmolality, and more so in stationary cells than in log cells. Genistein, a
      protein-tyrosine kinase inhibitor, caused a small increase in AIB uptake by log
      cells under both iso- and hyperosmotic conditions, but had no effect on AIB
      uptake by stationary cells. Genistein also caused a small increase in the rate of
      release of AIB in response to a decrease in osmolality. Brief preincubation with
      glucose, glutamate or proline of cells that had been depleted of their osmolytes
      by prior exposure to hypo-osmolality caused an increase in AIB release by log
      cells, but a decrease by stationary cells. Similarly, whereas glucose and
      glutamate increased the rate of AIB uptake by log cells, and proline inhibited
      it, they had no effect on AIB uptake by stationary cells. Thus AIB uptake and
      release are sensitive to changes in osmolality, to protein kinase inhibitors, and
      to certain nutrients in a manner that changes markedly with culture age.

PMID- 9004490
TI  - The tubulin gene family of Paramecium: characterization and expression of the
      alpha PT1 and alpha PT2 genes which code for alpha-tubulins with unusual C
      terminal amino acids, GLY and ALA.
AB  - The ciliated protozoan Paramecium harbours a particularly large diversity of
      microtubule networks, ranging from the elaborate and stable ciliary axonemes and
      basal bodies to very dynamic cytoplasmic, cortical or intranuclear arrays. Their
      organization and individual cycle of assembly/disassembly are well known and
      extensive immunocytochemical studies of the post-translational modifications in
      the various microtubule systems have been reported. However, in order to better
      understand the biogenesis of these multiple and diverse microtubule arrays, it
      seemed necessary to characterize the tubulin gene family. We show that P
      tetraurelia possesses four alpha- and three beta-genes and we report the cloning
      and sequencing of two intronless alpha-genes, alpha PT1 and alpha PT2, which code
      for very similar polypeptides, differing only by their unusual C-terminal amino
      acids, respectively GLY and ALA. Partial sequencing of the two other alpha-genes
      suggests an absence of any further isotype diversity. In an attempt to study the
      expression of alpha PT1 and alpha PT2, polyclonal antibodies were raised against
      the twelve C-terminal amino acids corresponding to the deduced polypeptide
      sequences. The reactivity of these anti-sequence antibodies was studied on blots
      of soluble tubulin and in situ and compared with that of other well characterized
      anti-alpha-tubulin antibodies. The molecular data show that in Paramecium, like
      in other ciliates, microtubule diversity does not arise from tubulin isotype
      diversity. The immunocytological data indicate that the native C-terminal
      sequences are predominantly detected in transient or nascent microtubule arrays
      and lead us to propose: 1) that the C-terminal TYR, absent in Paramecium and in
      most cilate species, has no intrinsic functional role; and 2) that post
      translational modifications do not seem directly instrumental in the geometry and
      functions of microtubule arrays.

PMID- 9004492
TI  - A hypolipidemic peroxisome proliferating fatty acid induces polydispersity of rat
      liver mitochondria.
AB  - Primary rat hepatocyte cultures exposed to tetradecylthioacetic acid for periods
      up to 96 h significantly increased fatty acid oxidation and decreased
      triacylglycerol synthesis and secretion. During the same period the mean areal
      fraction (%) and polydispersity of both mitochondria and peroxisomes increased,
      indicating growth and proliferation. In rats fed tetradecylthioacetic acid for 12
      weeks, the fatty acid oxidation increased with a concomitant hypolipidemic
      effect. In addition, the areal fraction of both mitochondria and peroxisomes
      increased significantly and the number of lipid droplets decreased. The results
      suggest that tetradecylthioacetic acid affects mitochondria and peroxisomes both
      in vitro and in vivo. It is concluded that tetradecylthioacetic acid reduces
      secretion of triacylglycerol from rat hepatocytes both in vitro and in vivo
      mainly by stimulating fatty acid oxidation.

PMID- 9004491
TI  - Macrophage mediated processing of an exogenous antigenic fluorescent probe: time
      dependent elucidation of the processing pathway.
AB  - To elucidate time-dependent pathways and mechanisms involved in antigen
      processing, a fluorescent probe suitable to monitor several steps within this
      pathway was developed. Previous studies utilizing two-photon fluorescence
      microscopy with time resolved and intensity imaging demonstrated that the probe,
      fluorescein derivatized BSA, was localized to the endocytic system and degraded
      over an extended period of time. However, an additional method, flow cytometry,
      was required to monitor the kinetics of these intracellular events and to better
      assess the total cell population. Flow cytometric studies indicated that the
      antigen entered an acidic intracellular environment consistent with the endocytic
      system of the macrophage. Additional experiments suggested that minimal
      proteolytic degradation began 10 min after addition of the antigenic probe while
      extensive enzymatic degradation did not occur until 180-200 min. Inhibitor
      studies indicated that degradation of the probe was dependent upon both acidic pH
      and ATP synthesis as well as all four classes of proteases. Experiments involving
      specific protease inhibitors also revealed that various classes of proteases were
      active at different time points throughout the processing of the probe. By
      combining these results with additional kinetic data, a model for the sequence of
      events involved in the processing of FITC10BSA was proposed. More importantly,
      these studies represented some of the first time-dependent kinetic measurements
      of antigen processing in living cells.

PMID- 9004493
TI  - Hyperplasia, hyperproliferation and decreased migration rate of colonic
      epithelial cells in mice fed a diet deficient in vitamin D.
AB  - Low serum levels of vitamin D metabolites have been associated with an increased
      risk for colon cancer. To investigate the effects of vitamin D deficiency on the
      colon, 4-week-old mice were fed a diet either containing (100,000 IU/kg diet) or
      lacking this vitamin for 3 weeks. Food consumption and body weight gain were
      similar in both groups. Following injection with 3H-thymidine to label dividing
      cells, cellular proliferation and migration up the colonic crypt were determined
      autoradiographically. Although overall crypt lengths were similar in both groups,
      there was hyperplasia and hyperproliferation in crypts of the deficient animals.
      Also, their epithelial cells migrated up the crypt at a significantly slower rate
      (maximum 0.78 micron/h) than did those from control mice (1.42 microns/h). There
      was no difference in cellularity, proliferation or migration in duodenal
      epithelium. These results indicate that vitamin D deficiency significantly alters
      colonic but not duodenal epithelial cells.

PMID- 9004494
TI  - Field and laboratory studies on the timing of oviposition and hatching of the
      western black-legged tick, Ixodes pacificus (Acari: Ixodidae).
AB  - The timing of oviposition and hatching of Ixodes pacificus was investigated in
      the field and at constant temperatures in the laboratory. Replete females held at
      temperatures between 9 and 29 degrees C began depositing eggs a mean of 9-70 days
      after drop off. Egg masses held between 12 and 25 degrees C commenced hatching 25
      178 days after the onset of oviposition. Eggs held at 9 or 29 degrees C did not
      hatch. The lower temperature thresholds for development (LTD) for oviposition and
      hatching were 6.5 and 9 degrees C, respectively. The number of degree days
      required for oviposition and hatching was 173 and 588, respectively. Replete
      females placed in the field on 2 December through to 8 March deposited eggs from
      2 February through to 24 April; the eggs commenced hatching between 2 July and 21
      August. Unfed larvae from two of 20 egg masses survived through the winter and
      fed readily when exposed to deer mice (Peromyscus maniculatus) on 22 April.
      Replete larvae were returned to the field and moulted between 9 and 21 August.
      Larvae exposed to deer mice in August, 4 weeks after hatching, also fed readily.
      Although further studies are needed to clarify the timing of nymphal development,
      the present study suggests that I. pacificus requires more than 1 year to
      complete its life cycle.

PMID- 9004496
TI  - Thermodynamic limitations on the resolution obtainable with metal replicas.
AB  - The major factor limiting resolution of metal-shadowed surfaces for electron and
      scanning tunnelling microscopy is the granularity of the metal film. This
      granularity had been believed to result from a recrystallization of the
      evaporated film, and hence could be limited by use of higher melting point
      materials for replication, or inhibited by adding carbon or other impurities to
      the film. However, evaporated and sputtered films of amorphous metal alloys that
      do not crystallize also show a granularity that decreases with increasing alloy
      melting point. A simple thermodynamic analysis shows that the granularity results
      from a dewetting of the typically low surface energy sample by the high surface
      energy metal film, similar to the beading up of drops of spilled mercury. The
      metal granularity and the resulting resolution of the metal-coated surface is
      proportional to the mobility of the metal on the surface after evaporation, which
      is related to the difference in temperature between the melting point of the
      metal and the sample surface temperature.

PMID- 9004495
TI  - Preliminary studies on virus and spirochete accumulation in the cement plug of
      ixodid ticks.
AB  - We provide evidence that tick-borne encephalitis virus and Borrelia burgdorferi
      s.l. are accumulated in the cement plug in the host skin within the first few
      hours after tick attachment. Extirpation of the tick without the cement plug,
      even very soon after the attachment, did not prevent the transmission by Ixodes
      ricinus, Ixodes persulcatus or Dermacentor reticulatus to mice. This was within 1
      hour in the case of the TBE virus and after 20-22 h of attachment, in the case of
      Borrelia and I. persulcatus. The epidemiological significance of these findings
      is discussed.

PMID- 9004497
TI  - Microbial utilization of human signalling molecules.

PMID- 9004498
TI  - Metabolic adaptation of Trichomonas vaginalis to growth rate and glucose
      availability.
AB  - The parasitic protist Trichomonas vaginalis adapted the specific activities of
      twelve of the enzymes involved in glucose metabolism to the growth rate an
      glucose availability. These changes in enzyme activities were induced by
      culturing T. vaginalis in chemostats with glucose, present in rate-limiting or
      excess concentrations, as carbon and energy source. The specific activities were
      measured in pelleted cells at each steady state, while metabolic end products
      were determined in filtered culture fluid. The specific activities were lower in
      cells grown on growth-rate-limiting concentrations of glucose and higher in
      organisms cultured in the presence of excess glucose. In both cases enzyme
      activities were higher at increasing growth rates. For most enzymes the
      difference between the highest and lowest activities was an order of magnitude.
      The specific activities of eleven of the enzymes were strongly correlated to each
      other (correlation coefficients 0.83-0.99), the exception being lactate
      dehydrogenase. The rates of production of the three major end products, lactate,
      acetate and glycerol, increased with increasing growth rates. Alanine was not
      formed in measurable quantities. The ratio of the end products formed was
      strongly influenced by the growth rates and glucose availability. The rates of
      formation of acetate and glycerol correlated best with the specific activities of
      the enzymes catalysing the final reactions of their respective pathways. This
      suggests that the production of acetate and glycerol is rate-limited by these
      final steps. In contrast, the formation of lactate did not correlate with the
      specific activity of lactate dehydrogenase but was determined by the rate of
      glucose consumption.

PMID- 9004500
TI  - Insertional gene inactivation in a phototrophic sulphur bacterium: APS-reductase
      deficient mutants of Chromatium vinosum.
AB  - In purple sulphur bacteria of the family Chromatiaceae sulphite oxidation via
      intermediary formation of adenylylsulphate is an enzymologically well
      characterized process. In contrast, the role of an alternative direct oxidation
      pathway via the enzyme sulphite:acceptor oxidoreductase has not been resolved.
      This paper reports the cloning of the genes encoding the adenylylsulphate-forming
      enzyme adenosine-5'-phosphosulphate (APS) reductase from Chromatium vinosum
      strain D (DSM 180'), a representative of the purple sulphur bacteria, and the
      construction of mutations in these genes by insertion of a kanamycin omega
      cartridge. The mutated genes were transferred to C. vinosum on suicide vectors of
      the pSUP series by conjugation and delivered to the chromosome by double
      homologous recombination. Southern hybridization and PCR analyses of the
      recombinants obtained verified the first insertional gene inactivation in purple
      sulphur bacteria. Enzymological studies demonstrated the absence of APS reductase
      from the mutants. Further phenotypic characterization showed no significant
      effect of APS reductase deficiency on the sulphite-oxidizing ability of the cells
      under photolithoautotrophic growth conditions. In the wild-type as well as in
      mutant strains, tungstate, the specific antagonist of molybdate, led to the
      intermediary accumulation of sulphite in the medium during sulphide oxidation and
      strongly inhibited growth with sulphite as photosynthetic electron donor; this
      indicates that a molybdoenzyme, probably sulphite:acceptor oxidoreductase, is the
      main sulphite-oxidizing enzyme in C. vinosum. Specific inactivation of selected
      genes as developed for C. vinosum in this study provides a powerful genetic tool
      for further analysis of sulphur metabolism and other metabolic pathways in
      phototrophic sulphur bacteria.

PMID- 9004499
TI  - Molecular cloning of the Corynebacterium glutamicum ('Brevibacterium
      lactofermentum' AJ12036) odhA gene encoding a novel type of 2-oxoglutarate
      dehydrogenase.
AB  - The Corynebacterium glutamicum ('Brevibacterium lactofermentum' AJ12036) odhA
      gene, encoding 2-oxoglutarate dehydrogenase (E1o subunit of the 2-oxoglutarate
      dehydrogenase complex), has been isolated and identified as an homologous
      counterpart of the Escherichia coll sucA and Bacillus subtilis odhA genes. The
      nucleotide sequence of a 4394 bp chromosomal fragment containing the C.
      glutamicum odhA gene was determined. The odhA gene comprised 3771 bp (1257
      codons, including the initiation codon) and a molecular mass of 138656 Da was
      predicted for the OdhA polypeptide. Northern blot analysis revealed a 3.9 kb
      transcript. The size of the transcript, together with the presence of a rho
      independent terminator-like structure, suggests that C. glutamicum odhA is
      monocistronic. Cells harbouring plasmids carrying C. glutamicum odhA showed a
      threefold increase in specific 2-oxoglutarate dehydrogenase complex activity and
      expression of a protein with an apparent molecular mass of 136 kDa, in good
      agreement with the predicted size of the OdhA polypeptide. The C-terminal region
      of the C. glutamicum OdhA protein shows strong sequence similarity to E1os from
      other organisms. C. glutamicum OdhA has an N-terminal extension not found in
      previously reported E1os. The amino acid sequence of this extension shows
      similarity to that of the C-terminal region of dihydrolipoamide S
      succinyltransferase (E2o) subunits of 2-oxoglutarate dehydrogenase complexes and
      dihydrolipoamide S-acetyltransferase (E2p) subunits of pyruvate dehydrogenase
      complexes. It suggests that the C. glutamicum odhA gene might encode a novel
      bifunctional protein with E1o and E2o activities.

PMID- 9004501
TI  - The cytochrome bc1 complex but not CycM is necessary for symbiotic nitrogen
      fixation by Rhizobium leguminosarum.
AB  - Following Tn5 mutagenesis of Rhizobium leguminosarum biovar viciae, two mutants
      in one complementation group were identified as being unable to fix nitrogen in
      pea nodules. Spectroscopic analysis revealed that the mutants had lowered levels
      of c-type cytochromes and cytochromes aa3, but increased levels of cytochrome d.
      Cells of the mutants were greatly reduced in their ability to oxidize the
      artificial electron donor N,N,N',N'-tetramethyl-p-phenylenediamine but membranes
      prepared from them had increased levels of succinate- and NADH-dependent
      respiration. NADH oxidation by the mutants was insensitive to the respiratory
      inhibitor antimycin A, that targets the cytochrome bc1 complex. Molecular
      analysis of the mutants revealed that they were affected in the cytochrome bc1
      complex. One of the mutants contained Tn5 in a gene homologous to that encoding
      cytochrome c1, and in the other the Tn5 was in DNA homologous to that encoding
      the cytochrome b component of the cytochrome bc1 complex. Haem staining revealed
      that haem proteins of M(r)31,000 and M(r)23,000 were absent from membranes from
      the mutants whereas an additional soluble c-type cytochrome protein of M(r)23,000
      was present. We conclude that the larger of these two haem proteins corresponds
      to cytochrome c1 and, in its absence, the protein of M(r)23,000 does not remain
      associated with the membrane. Formation of this M(r)23,000 component was
      specifically blocked in a third respiratory-defective mutant which contained Tn5
      in a region of DNA showing homology to a Bradyrhizobium Japonicum gene previously
      shown to encode the membrane-bound c-type cytochrome CycM. Although the
      cytochrome bc1 complex is essential for symbiotic nitrogen fixation, the other
      membrane-bound c-type cytochrome (CycM) is not.

PMID- 9004502
TI  - The antibacterial action of protamine: evidence for disruption of cytoplasmic
      membrane energization in Salmonella typhimurium.
AB  - Protamine is a polycationic peptide found in the nuclei of sperm of different
      animal species. While it has long been known to have antimicrobial properties,
      its mode of action has remained elusive. We have investigated the mechanism of
      action of protamine and established that this peptide exerts its antibacterial
      effect without causing cell lysis or permeabilization of the cytoplasmic
      membrane. Respiring cells were more susceptible than nonrespiring cells, and loss
      of viability could be prevented by incubation at low pH or the addition of
      respiratory poisons. This indicates that protamine activity is influenced by the
      electrical membrane potential (delta psi): increased killing occurs at higher
      delta psi values. Protamine caused inhibition of proline uptake, rapid efflux of
      proline from preloaded cells, and a reduction in the cellular ATP content.
      Furthermore, protamine-treated cells first lost the ability to accumulate leucine
      and then could not carry out protein synthesis. Cumulatively, our data indicate
      that protamine disrupts energy transduction and nutrient uptake functions, and
      suggest that the cytoplasmic membrane is the target of protamine action.

PMID- 9004503
TI  - Identification of an overexpressed yeast gene which prevents aminoglycoside
      toxicity.
AB  - Aminoglycoside antibiotics, used to treat bacterial infections by interfering
      with proofreading during protein synthesis, cause sensorineural hearing loss in
      genetically susceptible individuals. The only aminoglycoside-hypersensitivity
      mutations which have been described in humans are in the mitochondrial 125 rRNA
      gene, potentially allowing increased antibiotic binding to mitochondrial
      ribosomes. To identify additional predisposing mutations, a yeast model system
      was used to isolate genes which interact with or bypass the effects of
      aminoglycoside antibiotics. A novel yeast gene was isolated which, in high copy,
      confers neomycin resistance to yeast transformants. The neomycin-resistance 1
      gene (NEO1) encodes a potential 1151 as integral membrane protein, most
      homologous to the yeast DRS2 gene product, a Ca(2+)-ATPase involved in
      cytoplasmic ribosome assembly. The N-terminus of Neo1p is partially homologous to
      abrin A-chain, another protein which interacts with cytoplasmic ribosomes.
      Mutagenesis experiments demonstrate that the NEO1 product is essential for
      vegetative growth and that the drug-resistance phenotype requires ATPase
      function.

PMID- 9004504
TI  - Structural and functional organization of the Yersinia pestis bacteriocin
      pesticin gene cluster.
AB  - The primary structure of a 2671 bp DNA fragment between the pla gene (encoding
      plasminogen activator) and the origin of replication of the wild-type Yersinia
      pestis plasmid pYP358 was determined. Two ORFs of 1074 and 426 bp with opposite
      transcription polarities were identified on both strands. They encode a 357 aa
      pesticin activity protein (Pst) and a 141 aa pesticin immunity polypeptide (Pim).
      A GC-rich palindromic structure located between pst and pim can form a hairpin
      loop and serve as rho-independent transcription terminator sequences for both
      genes. The site for the interaction with the LexA repressor of the SOS system was
      found in another palindromic structure preceding the pst structural gene. A
      deduced 39.9 kDa Pst polypeptide is devoid of a signal peptide, indicating a Sec
      independent mode of export. Pst carries a pentapeptide typical of TonB-dependent
      colicins (TonB box) that is necessary for the interaction with the
      yersiniabactin/pesticin receptor and for active energy-dependent transport
      through the outer membrane. The substitution of the last five C-terminal amino
      acids did not significantly influence the bactericidal activity of the truncated
      pesticin. The pesticin lost its ability to kill sensitive bacteria and to bind to
      a pesticin receptor after deletion of the last 57 C-terminal amino acids. A
      deduced 16 kDa Pim protein has an N-terminal hydrophobic amino acid stretch with
      features typical of prokaryotic signal peptides. Pim is a slightly hydrophilic
      protein with a basic pl. The immunity protein was localized in the periplasmic
      space and in the outer-membrane fraction after its overexpression under the
      polymerase T7 promoter. Several other ORFs were identified on the sequenced 2671
      bp fragment, but none of them seemed to encode a typical lysis peptide, which is
      necessary for the release of the pesticin. In the promoter region and in the
      regions preceding and following the pst operon, the DNA sequence has high (> 70%)
      identity with other colicin genes. The DNA sequence located 284 bp upstream of
      the pim gene showed more than 90% similarity to antisense RNA I of the ColE1
      replicon. This defined the location of the pYP358 origin of ColE1-type
      replication.

PMID- 9004505
TI  - Genotypic and phenotypic analysis of zwittermicin A-producing strains of Bacillus
      cereus.
AB  - Many strains of Bacillus cereus produce zwittermicin A, a novel antibiotic that
      contributes to the ability of B. cereus to suppress certain plant diseases. The
      purpose of this study was to identify molecular indicators of zwittermicin A
      production in B, cereus strains, contribute to an understanding of the ecology
      and evolution of this group of bacteria, and identify potential agents for
      control of plant disease. The fatty acid composition of 20 strains known to be
      zwittermicin A producers and 20 strains known to be non-producers was determined.
      Cluster analysis of the fatty acid methyl ester (FAME) profiles revealed that
      zwittermicin A producers grouped together in two clusters, apart from most non
      producers. Discriminant analysis of the FAME profiles generated models that
      correctly predicted the zwittermicin A-production phenotype in 17 of 20
      zwittermicin A producers and 17 of 20 non-producers. Sixteen random
      oligonucleotide primers were tested in PCR, and one primer was identified that
      generated a fragment of 0.48 kb or 0.49 kb from total DNA from 26 of 28 strains
      known to produce zwittermicin A, whereas PCR with this primer did not generate
      bands of that size from 16 of 20 non-producing strains. PCR with primers designed
      to amplify zmaR, a gene from B. cereus that confers resistance to zwittermicin A,
      generated DNA fragments of 1.1 kb and 1.0 kb in all 29 zwittermicin A-producing
      strains tested, amplified a fragment of 0.3 kb in some of the zwittermicin A
      producing strains, and amplified no fragments in 20 of 23 non-producing strains
      in a stock collection of B. cereus strains. The zmaR primers were tested for
      their ability to identify new zwittermicin A-producing isolates of B. cereus from
      two soils. All 12 of the isolates that produced the banding pattern
      characteristic of this primer pair produced zwittermicin A, and none of the 12
      isolates that did not have the banding pattern produced detectable zwittermicin
      A. Seven of the 12 isolates initially identified as zwittermicin A producers with
      the zmaR primers significantly suppressed damping-off of alfalfa, whereas only
      one of the non-producers suppressed this disease. The results show that FAME and
      PCR analyses distinguish B. cereus strains that produce zwittermicin A from other
      B. cereus strains, that PCR with the primers designed to amplify zmaR is the most
      reliable method of those tested for identification of zwittermicin A producers,
      and that this method can be used to identify new strains with disease-suppressive
      activity.

PMID- 9004506
TI  - The wprA gene of Bacillus subtilis 168, expressed during exponential growth,
      encodes a cell-wall-associated protease.
AB  - The nucleotide sequence of wprA, a protease-encoding gene of Bacillus subtilis
      168, is reported. The gene, expressed during the exponential growth phase,
      belongs to a monocistronic operon. WprA is a 96 kDa polypeptide endowed with a
      signal peptide, as well as a propeptide. Upon processing and export, it gives
      rise to two previously identified cell-wall-bound proteins, CWBP23 and 52.
      Processing of WprA exhibits a novel feature of protein export, whereby removal of
      the middle part of the molecule accompanies the targeting to the cell wall of its
      N- and C-terminal parts, which correspond to CWBP23 and 52, respectively.
      Sequence analyses and enzymic assays reveal that CWBP52 is a serine protease.
      Growth rate, cell morphology, sporulation and motility of wprA mutants apparently
      do not differ from those of the parent strain.

PMID- 9004507
TI  - Expression of the Bacillus subtilis spoIVB gene is under dual sigma F/sigma G
      control.
AB  - The expression of the Bacillus subtilis spoIVB gene, which encodes a
      developmental cell-cell signalling molecule, has been characterized. In some
      conditions, this gene can be transcribed by RNA polymerase associated with either
      sigma F or sigma G, in contrast to previous studies implying exclusive control by
      sigma G. However, during sporulation, only sigma G directs significant levels of
      spoIVB expression.

PMID- 9004508
TI  - An operon from Lactobacillus helveticus composed of a proline iminopeptidase gene
      (pepI) and two genes coding for putative members of the ABC transporter family of
      proteins.
AB  - A proline iminopeptidase gene (pepI) of an industrial Lactobacillus helveticus
      strain was cloned and found to be organized in an operon-like structure of three
      open reading frames (ORF1, ORF2 and ORF3). ORF1 was preceded by a typical
      prokaryotic promoter region, and a putative transcription terminator was found
      downstream of ORF3, identified as the pepI gene. Using primer-extension analyses,
      only one transcription start site, upstream of ORF1, was identifiable in the
      predicted operon. Although the size of mRNA could not be judged by Northern
      analysis either with ORF1-, ORF2- or pepI-specific probes, reverse transcription
      PCR analyses further supported the operon structure of the three genes. ORF1,
      ORF2 and ORF3 had coding capacities for 50.7, 24.5 and 33.8 kDa proteins,
      respectively. The ORF3-encoded PepI protein showed 65% identity with the PepI
      proteins from Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus
      delbrueckii subsp. lactis. The ORF1-encoded protein had significant homology with
      several members of the ABC transporter family but, with two distinct putative ATP
      binding sites, it would represent an unusual type among the bacterial ABC
      transporters. ORF2 encoded a putative integral membrane protein also
      characteristic of the ABC transporter family. The pepI gene was overexpressed in
      Escherichia coli. Purified PepI hydrolysed only di and tripeptides with proline
      in the first position. Optimum PepI activity was observed at pH 7.5 and 40
      degrees C. A gel filtration analysis indicated that PepI is a dimer of M(r)
      53,000. PepI was shown to be a metal-independent serine peptidase having thiol
      groups at or near the active site. Kinetic studies with proline-p-nitroanilide as
      substrate revealed Km and Vmax values of 0.8 mM and 350 mmol min-1 mg-1,
      respectively, and a very high turnover number of 135,000 s-1.

PMID- 9004509
TI  - Lactobacillus curvatus has a glucose transport system homologous to the mannose
      family of phosphoenolpyruvate-dependent phosphotransferase systems.
AB  - In Lactobacillus curvatus, a phosphoenolpyruvate:mannose phosphotransferase
      system (mannose-PTS) has been characterized and it was shown to be involved in
      glucose and mannose transport, but no glucose-specific PTS activity could be
      detected. A 2.1 kb DNA fragment amplified by PCR from the L. curvatus genome was
      sequenced. Sequence analysis showed four ORFs which could encode proteins similar
      to PTS transporters EIIA, EIIB, EIIC and EIID of the mannose class. The
      expression of the manB gene (encoding EIIB) from L. curvatus in a mutant of
      Lactobacillus sake impaired in EIIMan activity restored this activity.
      Furthermore, this DNA fragment complemented the regulatory function of LevE
      (EIIB) in a Bacillus subtilis levE-deficient mutant, suggesting that the protein
      encoded by manB could also play a regulatory role in L. curvatus.

PMID- 9004510
TI  - Dynamics of the population structure of Bordetella pertussis as measured by
      IS1002-associated RFLP: comparison of pre- and post-vaccination strains and
      global distribution.
AB  - The effect of temporal and geographic factors on the population structure of
      Bordetella pertussis was studied using IS1002-based RFLP analysis. Among the 106
      strains analysed, 36 different RFLP types were observed. For the Dutch strains,
      there was evidence for a shift in the population structure in time since the
      majority of strains were found in different families of related strains in
      successive periods. Most pronounced were the differences observed between 1950
      1954 and later periods. This difference may have been caused by the introduction
      of the whole-cell vaccine in 1953, resulting in the expansion of strains which
      are less affected by vaccine-induced immunity. Strains with RFLP types identical
      to the vaccine strains were observed in the period 1950-1954, but not later,
      suggesting a decreased frequency of such strains due to vaccination. Analysis of
      strains from the 1994 Dutch pertussis epidemic revealed that 71% of the strains
      belonged to two RFLP types, indicating that pertussis epidemics are caused by
      clonal expansion. IS1002-based RFLP analysis of strains from different countries
      suggested a partial geographic isolation of B. pertussis populations. One RFLP
      type was found to have a wide distribution in time and in space.

PMID- 9004511
TI  - Neutrophil depletion increases susceptibility to systemic and vaginal candidiasis
      in mice, and reveals differences between brain and kidney in mechanisms of host
      resistance.
AB  - Infections caused by the yeast Candida albicans represent an increasing threat to
      debilitated and immunosuppressed patients, and neutropenia is an important risk
      factor. Monoclonal antibody depletion of neutrophils in mice was used to study
      the role of these cells in host resistance. Ablation of neutrophils increased
      susceptibility to both systemic and vaginal challenge. The fungal burden in the
      kidney increased threefold on day 1, and 100-fold on day 4, and infection was
      associated with extensive tissue destruction. However, a striking feature of the
      disseminated disease in neutrophil-depleted animals was the altered pattern of
      organ involvement. The brain, which is one of the primary target organs in normal
      mice, was little affected. There was a threefold increase in the number of
      organisms recovered from the brains of neutrophil-depleted mice on day 4 after
      infection, but detectable abscesses were rare. In contrast, the heart, which in
      normal mice shows only minor lesions, developed severe tissue damage following
      neutrophil depletion. Mice deficient in C5 demonstrated both qualitative and
      quantitative increases in the severity of infection after neutrophil depletion
      when compared with C5-sufficient strains. The results are interpreted as
      reflecting organ-specific differences in the mechanisms of host resistance.

PMID- 9004512
TI  - An antigenic water-soluble glucogalactomannan extracted from cell walls of
      Paecilomyces fumosoroseus and Paecilomyces farinosus.
AB  - The water-soluble fraction (F1S) obtained after solubilizing in alkali the cell
      walls of four strains of Paecilomyces fumosoroseus and two of Paecilomyces
      farinosus amounted to 8.3-14.5% of the dry cell wall material. Two
      polysaccharides, F1S-A (13-20%) and F1S-B (57-68%) were separated from F1S by gel
      permeation through Sepharose CL-6B. 1H and 13C NMR spectra of F1S-B were recorded
      and showed analogous structural features in the six isolates of the two species.
      The fractions isolated from P. fumosoroseus strain CBS 375.70 were subjected to
      structural analysis and shown to be a (1-->4)-alpha-glucan (F1S-A) and a branched
      (1-->6)-mannan with terminal residues of beta-galactopyranose (F1S-B). Polyclonal
      antibodies against the latter polysaccharide were obtained (titre 1/8000). These
      antibodies reacted specifically with the F1S-B polysaccharides obtained from the
      four strains of P. fumosoroseus and the two strains of P. farinosus, but they did
      not react with similar fractions from other species of the same or related
      genera. The antibodies specifically stained P. fumosoroseus hyphae in indirect
      immunofluorescence tests.

PMID- 9004514
TI  - Characterization of the gene for an immunodominant 72 kDa lipoprotein of
      Mycoplasma mycoides subsp. mycoides small colony type.
AB  - With the aim of characterizing specific immunogenic proteins of Mycoplasma
      mycoides subsp. mycoides small colony (SC) type, the aetiological agent of
      contagious bovine pleuropneumonia, a gene encoding a major immunogenic protein of
      72 kDa named P72 was cloned and expressed in Escherichia coli. The expressed
      protein was of the same apparent molecular mass as that produced by the parent
      strain. The predicted molecular mass of P72, based on the DNA-deduced amino acid
      sequence, was 61.118 kDa, significantly lower than the apparent molecular mass of
      endogenous or recombinant P72 on SDS-PAGE. Analysis of the amino acid sequence
      revealed a typical prokaryotic signal peptidase II-membrane lipoprotein lipid
      attachment site and a transmembrane structure domain in the leader sequence at
      the amino-terminal end of the protein. P72 was shown to be a lipoprotein and its
      surface location was confirmed by trypsin treatment of whole cells. An unassigned
      gene encoding a peptide with some similarity to P72 was found on the genome
      sequence of M. capricolum subsp. capricolum but not on that of Mycoplasma
      genitalium. The P72 gene was detected in 11/11 M. mycoides subsp. mycoides SC
      strains. Antiserum against recombinant P72 reacted strongly with 12/12 strains of
      M. mycoides subsp. mycoides SC, weakly with Mycoplasma bovine group 7 strain
      PG50, but not with other members of the 'mycoides cluster' or closely related
      mycoplasmas. Cows experimentally contact-infected with M. mycoides subsp.
      mycoides SC developed a humoral response against P72 within 35 d. P72 is a
      specific antigenic membrane lipoprotein of M. mycoides subsp. mycoides SC with
      potential for use in development of diagnostic reagents. It seems to belong to a
      family of lipoproteins of the "mycoides cluster'.

PMID- 9004515
TI  - Phylogenetic diversity of intra-amoebal legionellae as revealed by 16S rRNA gene
      sequence comparison.
AB  - Following a recent phylogenetic analysis of all 39 species of the genus
      Legionella and related organisms, the name Legionella lytica has been proposed
      for bacteria previously considered either as Sarcobium lyticum or as 'Legionella
      like amoebal pathogens' (LLAPs). To investigate the phylogenetic integrity of
      this newly proposed species, we determined the 16S rRNA gene sequences of 10
      LLAPs isolated from various environmental sources. All 10 isolates clustered
      within a monophyletic group containing all other members of the genus Legionella.
      Eight of the 10 isolates formed a monophyletic subgroup within the genus which
      also included the two previously characterized L. lytica strains. Four of these
      10 isolates shared a specific and very close relationship with the L. lytica type
      strain (> 99% sequence similarity). However, although clearly legionellae, the
      remaining two LLAP strains bore no specific evolutionary relationship to either
      L. lytica or any other Legionella species (< 96% sequence similarity). Both
      isolates lay on their own relatively deep-rooted branches within the radiation of
      the Legionella cluster. LLAPs do not, therefore, represent a unique species or
      even a single line of descent within the genus, and investigation of more
      isolates may reveal them to be as evolutionarily diverse as the other presently
      recognized Legionella species.

PMID- 9004513
TI  - Conservation and antigenic cross-reactivity of the transferrin-binding proteins
      of Haemophilus influenzae, Actinobacillus pleuropneumoniae and Neisseria
      meningitidis.
AB  - Haemophilus influenzae acquires iron from the iron-transporting glycoprotein
      transferrin via a receptor-mediated process. This involves two outer-membrane
      transferrin-binding proteins (Tbps) termed Tbp1 and Tbp2 which show considerable
      preference for the human form of transferrin. Since the Tbps are attracting
      considerable attention as potential vaccine components, we used transferrin
      affinity chromatography to examine their conservation amongst 28 H. influenzae
      type b strains belonging to different outer-membrane-protein subtypes as well as
      six non-typable strains. Whole cells of all type b and non-typable strains
      examined bound human transferrin; whilst most strains possessed a Tbp1 of
      approximately 105 kDa, the molecular mass of Tbp2 varied from 79 to 94 kDa.
      Antisera raised against affinity-purified native H. influenzae Tbp1/Tbp2 receptor
      complex cross-reacted on Western blots with the respective Tbps of all the
      Haemophilus strains examined. When used to probe Neisseria meningitidis Tbps,
      sera from each of four mice immunized with the Haemophilus Tbp1/2 complex
      recognized the 68 kDa Tbp2 of N. meningitidis strain B16B6 but not the 78 kDa
      Tbp2 of N. meningitidis strain 70942. Serum from one mouse also reacted weakly
      with Tbp1 of strain B16B6. Apart from a weak reaction with the Tbp2 of a serotype
      5 strain, this mouse antiserum failed to recognize the Tbps of the porcine
      pathogen A. pleuropneumoniae. However, a monospecific polyclonal antiserum raised
      against the denatured Tbp2 of Neisseria meningitidis B16B6 recognized the Tbps of
      all Haemophilus and Actinobacillus strains examined. Since H. influenzae forms
      part of the natural flora of the upper respiratory tract, human sera were
      screened for the presence of antibodies to the Tbps. Sera from healthy adults
      contained antibodies which recognized both Tbp1 and Tbp2 from H. influenzae but
      not N. meningitidis. Convalescent sera from meningococcal meningitis patients
      contained antibodies which, on Western blots, recognized the Tbps2s of both
      pathogens. These data demonstrate the existence of shared epitopes on the Tbps of
      H. influenzae, N. meningitidis and A. pleuropneumoniae despite their transferrin
      species specificity.

PMID- 9004516
TI  - Relatedness structure detected by microsatellite analysis and attempted pedigree
      reconstruction in an endangered marsupial, the northern hairy-nosed wombat
      Lasiorhinus krefftii.
AB  - The northern hairy-nosed (NHN) wombat is perhaps Australia's most endangered
      mammal. Being fossorial and nocturnal as well as rare, NHN wombats are difficult
      to observe in the wild. Hence little is known of their social biology, such as
      their mating and dispersal systems. A hypothesis has been advanced that adult
      females of the species disperse post-breeding, leaving their young to inhabit the
      natal burrow. Female-biased dispersal is expected to result in higher relatedness
      amongst males in a burrow cluster than amongst females in a burrow cluster. The
      usefulness of a panel of microsatellite markers in estimating the relatedness
      structure, and in reconstructing pedigrees for, the sole known population of NHN
      wombats was assessed. Microsatellite genotypes at eight or nine loci were
      obtained from 58 of the 85 known individuals, and used to estimate pairwise
      individual relatedness using Queller & Goodnight's (1989) RELATEDNESS 4.2. Our
      analysis gave the unexpected result that both males and females were
      significantly more closely related to their same-sex burrow cluster mates than
      random, while opposite-sex animals sharing burrows were only slightly
      (nonsignificantly) more related than random. This raises the possibility of
      dispersal patterns which lead to association of same-sex relatives. The observed
      relatedness structure is not expected to make likely a high incidence of inbred
      matings, as close relatives of the opposite sex are not significantly associated
      in space. Parentage analysis was attempted using genetic exclusion and LOD
      likelihood ratios, but proved difficult because of low genetic variation,
      incomplete sampling of potential parents, and paucity of ecological data such as
      known mother/offspring pairs and ages of individuals.

PMID- 9004517
TI  - Genetic differences between the endangered San Clemente Island loggerhead shrike
      Lanius ludovicianus mearnsi and two neighbouring subspecies demonstrated by mtDNA
      control region and cytochrome b sequence variation.
AB  - We investigated mtDNA sequence variation in five populations of the loggerhead
      shrike Lanius ludovicianus, representing four subspecies, including the San
      Clemente logger-head shrike L. l. mearnsi, a critically endangered California
      Channel Island endemic. Variability in 200 bp of control region and 200 bp of
      cytochrome b was extremely low, and defined four haplotypes. Strong structure was
      apparent among all three southern California subspecies, including L. l. mearnsi,
      with one haplotype predominating in each subspecies. Although potential levels of
      gene flow between L. l. mearnsi and neighbouring populations are low, mtDNA data
      support field observations that some shrikes visit the island during winter but
      do not stay to breed, and suggest that these birds come from the mainland. The
      similarity in haplotypes between populations from Saskatchewan, Canada and those
      in southern California suggests post-glacial northern range expansion of the
      species. Our results confirm the evolutionary distinctiveness of L. l. mearnsi
      and justify continuing efforts for its conservation.

PMID- 9004518
TI  - PCP degradation is mediated by closely related strains of the genus Sphingomonas.
AB  - There have been numerous reports in the literature of diverse bacteria capable of
      degrading pentachlorophenol (PCP). In order to gain further insight into the
      phylogenetic relationships of PCP-degrading bacteria, we examined four strains:
      Arthrobacter sp. strain ATCC 33790, Flavobacterium sp. strain ATCC 39723,
      Pseudomonas sp. strain SR3, and Sphingomonas sp. strain RA2. These organisms were
      isolated from different geographical locations and all of them degrade high
      concentrations (100-200 mg/L) of PCP. Southern blot analyses determined that
      these bacteria all harbour DNA that encodes similar, if not identical, genes
      involved in PCP degradation. Comparison of the 16S rRNA nucleotide sequences
      revealed that these organisms were very closely related and, in fact, represent a
      monophyletic group. The 16S rRNA analyses together with fatty acid and
      sphingolipid analyses strongly suggest that the four strains are members of the
      genus Sphingomonas. The close relationship of the four organisms is supported by
      nucleotide sequence analysis data of the pcpB locus encoding PCP-4-monooxygenase,
      the first enzyme in the PCP degradative pathway.

PMID- 9004520
TI  - Isolation and characterization of six polymorphic microsatellite loci in the
      European hedgehog Erinaceus europaeus.

PMID- 9004519
TI  - Sex-related spatial kin structure in a spring population of grey-sided voles
      Clethrionomys rufocanus as revealed by mitochondrial and microsatellite DNA
      analyses.
AB  - Polymerase chain reaction-directed mitochondria (mt) and microsatellite DNA
      analyses were performed to examine the kin structure in a spring population of
      grey-sided voles Clethrionomys rufocanus in Hokkaido, Japan. The spatial
      distribution of 81 voles in a trapping grid (about 1 ha) was estimated by using
      the catch-mark-release method. DNA samples were extracted from the toes clipped
      for individual identification. Maternal lineages of voles were unequivocally
      determined by the mtDNA haplotypes, as identified by nucleotide sequencing of the
      control region. Relatedness between individuals was estimated based on the
      genotype and allele frequencies at several microsatellite loci. Although the
      distribution of voles was uniform within the grid, neighbouring females were
      frequently from the same maternal lineage. Relatedness values between females
      correlated negatively with geographical distances. Combination of the two
      molecular markers revealed four clusters of closely related, matrilineal females
      in the population, whereas no such cluster was apparent in males. The present
      study first demonstrated a sex-related spatial kin structure in a natural
      population of the grey-sided vole.

PMID- 9004521
TI  - Isolation and characterization of microsatellite loci in a Phylloscopus warbler.

PMID- 9004522
TI  - Isolation and characterization of hypervariable microsatellites in the red grouse
      Lagopus lagopus scoticus.

PMID- 9004523
TI  - Trinucleotide microsatellite loci for a social wasp, Polistes.

PMID- 9004524
TI  - A wide-range survey of cross-species microsatellite amplification in birds.

PMID- 9004525
TI  - Post-source decay fragment spectra of cyclomalto-octaose and branched cyclomalto
      hexaose by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - gamma-Cyclodextrin, maltosyl-alpha-cyclodextrin and diglucosyl-alpha-cyclodextrin
      were analyzed using matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) mass spectrometry. All of these compounds have the same molecular
      weight (M.W. = 1297.15) and consist of only D-glucopyranose. From a comparison of
      the intensities in the post-source decay (PSD) fragment spectra of these
      cyclodextrin derivatives, correlation between the chemical structures and the
      relative intensities in the PSD fragment ions was found. The correlation is
      considered to be caused by the difference in the number of cleavage sites at the
      glycosyl binding. It was found that the intensity of the PSD ion resulting from
      one cleavage is higher than that resulting from two cleavages at a glycosyl bond.
      The results show that PSD fragment-ion spectrum method used in MALDI-TOF mass
      spectrometry is a very powerful technique for the structural analyses of the
      sugar-substituted cyclodextrins.

PMID- 9004526
TI  - Identification of oxidized methionine in peptides.
AB  - The positive- and negative-ion collision-induced dissociation spectra of peptides
      containing methionine, methionine sulphoxide and methionine sulphone have been
      studied. Characteristic fragmentations were identified and evaluated as possible
      indicators for the presence of oxidized methionine residues in peptides. It was
      found that the elimination of CH3SOH (-64 u) from [M + H]+ is unique for peptides
      that contain methionine sulphoxide. Sequence ions containing the oxidized
      methionine undergo the same elimination, allowing unambiguous sequence
      determination. Methionine sulphone exhibits an analogous elimination of CH3SO2H (
      80 u) from the protonated molecule, but not from sequence ions.

PMID- 9004527
TI  - Procedures for tandem mass spectrometry on an ion trap storage/reflectron time-of
      flight mass spectrometer.
AB  - In this work, we demonstrate tandem mass spectrometry on an ion trap storage
      reflectron time-of-flight mass spectrometer (IT/reTOFMS). Ion isolation and
      activation were achieved by resonant excitation using multi- and single-frequency
      waveforms generated from an analog circuit. Product-ion spectra of small
      polypeptides are obtained, which are comparable in fragmentation to those
      acquired on sector or hybrid mass spectrometers. Several important parameters
      governing the tandem mass spectrometry process, including the activation tickle
      voltage, type of collision gas, activation period and cooling period after the
      fragmentation were optimized using leucine-enkephalin as a model. Although the
      limited energy deposition from collisional activation in our experiments does not
      allow efficient fragmentation of large singly charged polypeptides with m/z
      higher than 1000, the problem may be partially solved by taking advantage of
      fragmenting the multiply charged ions produced from the electrospray ionization
      source as demonstrated for a synthetic polypeptide of molecular weight 2782.
      Compared to the singly charged form, the reduced m/z of multiply charged forms
      experience a greater trapping force as described by the pseudopotential well
      depth model. Increased pseudopotential well-depths for multiply charged species
      permit the use of greater fragmentation energy at lower RF potentials. These
      conditions facilitate the fragmentation of large polypeptides, yet are suitable
      for trapping singly charged fragments. These experiments indicate that the high
      efficiency associated with ion dissociation and fragment-ion collection in the
      trap and the storage capability for detection of ions using the non-scanning mode
      of the IT/ reTOF analyzer may provide an alternative means for acquiring sequence
      specific information of polypeptides at low picomol levels of sensitivity.

PMID- 9004528
TI  - Effect of phase locking AC and RF voltages for high mass analysis in a quadrupole
      ion trap mass spectrometer.
AB  - Experiments on the influence of locking the AC and RF frequency phases on the
      mass resolution and line position in the mass spectra from a quadrupole ion trap
      mass spectrometer were carried out at low ejection values of beta z to
      investigate the possibility of using this effect for high mass analysis. At a
      typical mass scan rate of 1000 u/s the improvement for the mass resolution in
      these experiments did not exceed 10-20% at beta z = 0.25 compared with 200-250%
      at beta z = 0.5. However, without phase locking, the mass resolution at beta z =
      0.25 was about two times higher than that at beta z = 0.5. Thus, the absolute
      values for the mass resolution observed without phase-locked AC and RF
      frequencies at beta z = 0.25 were about the same as at beta z = 0.5 with phase
      locking. This observation was explained by a significant negative contribution to
      the mass resolution of the ion microoscillations along the trajectory at the
      fundamental RF frequency which is different for the cases of beta z = 0.25 and
      beta z = 0.5.

PMID- 9004529
TI  - Studies on the selection of new matrices for ultraviolet matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - A new group of compounds has been successfully tested as matrices for ultraviolet
      matrix-assisted laser desorption/ionization mass spectrometry (UV-MALDI MS).
      Several new matrices for UV-MALDI MS have been found by choosing, as potential
      matrices, compounds that perform an intramolecular proton transfer along an
      intramolecular H-bond under UV irradiation. Compounds of this type are, for
      example, salicylamide, salicylanilide, several ortho-hydroxyacetophenones and
      ortho-hydroxybenzophenones. The matrix activity of these compounds is compared to
      the corresponding meta- and para-isomers and to the matrix activity of such well
      known matrices as 2,5-dihydroxybenzoic acid and 2,4,6-trihydroxyacetophenone. It
      was found that meta- and para-substituted hydroxycarbonyl compounds show either a
      significantly lower or no matrix activity compared with the ortho isomers.

PMID- 9004530
TI  - The detection and characterization of analgesics and anti-inflammatory drugs on
      high performance thin-layer chromatography plates using tandem mass spectrometry:
      application to drugs and metabolites in urine.
AB  - The application of tandem mass spectrometry to the analysis and identification of
      analgesics and non-steroidal anti-inflammatory drugs such as paracetamol,
      ibuprofen and indomethacin following thin-layer chromatography (TLC) is
      described. TLC was combined successfully with mass spectrometry and with tandem
      mass spectrometry using silica gel and diol-bonded silica gel high performance
      TLC plates. The diol-bonded phase was found to be superior for use with
      biological samples and enabled the identification of paracetamol, ibuprofen and
      salicylhippuric acid (the major metabolite of acetylsalicylic acid) in human
      urine extracts following normal therapeutic doses.

PMID- 9004531
TI  - Rapid identification of bacteria by direct matrix-assisted laser
      desorption/ionization mass spectrometric analysis of whole cells.
AB  - Several characteristic ions were observed during the direct analysis of a variety
      of both gram-negative and gram-positive intact bacterial cells by the matrix
      assisted laser desorption/ionization mass spectrometry (MALDI-MS) technique. The
      entire process, involving absolutely no sample processing, could be completed in
      less than ten minutes. A number of specific biomarkers, generated reproducibly
      for each type of cell from the corresponding mass spectrum, permitted the
      identification, as well as the distinction, of pathogenic bacteria from their non
      pathogenic counterparts. In addition, individual strains of a specific organism
      could also be differentiated easily. Some of these biomarkers correspond to those
      observed earlier during the MALDI-MS analysis of protein extracts of the same
      bacteria. This approach, which can yield valuable data for rapid classification
      and detection of microorganisms, represents a substantial breakthrough for rapid
      screening of environmental as well as biological samples.

PMID- 9004532
TI  - Sealing of the follicular lumen of the anterior pituitary gland of the male rat.
AB  - It is commonly accepted that follicular lumina of the adult rat anterior
      pituitary gland are tightly sealed by junctional complexes, especially tight
      junctions. In this report, we describe the presence of follicular lumina that are
      unsealed. Peroxidase (HRP) was used to study such structures and when injected
      through the femoral vein, was observed in association with a few follicular
      lumina, on their microvilli and around the cilia of folliculo-stellate cells. The
      existence of peroxidase-positive follicles clearly shows that follicles of the
      hypophysis are not always firmly sealed by tight junctions. The folliculo
      stellate cells which faced the peroxidase-positive follicles displayed HRP
      deposits which were membrane bound within their cytoplasm. These findings suggest
      an absorptive function for the folliculo-stellate cells.

PMID- 9004533
TI  - Immunohistochemical localization of facilitated-diffusion glucose transporters in
      rat pancreatic islets.
AB  - The subcellular localization of five isoforms of facilitated-diffusion glucose
      transporters (GLUTs), from GLUT1 to GLUT5, in rat pancreatic islets was studied
      by immunohistochemistry using rabbit polyclonal antisera against mouse or rat
      GLUT peptides. Animals were perfusion-fixed with phosphate-buffered 4%
      paraformaldehyde and the pancreases were removed. Some specimens were embedded in
      paraffin, serially sectioned, and immunostained for glucagon, insulin,
      somatostatin, and the GLUTs for light microscopic observation. Others were
      prepared for immunoelectron microscopy by the post-embedding method. By these
      methods, GLUT2 immunostaining was observed on the lateral membranes of pancreatic
      beta-cells, whereas GLUT3 immunoreaction was predominantly localized in the
      cytoplasm of beta-cells and was not found in alpha-cells. In contrast, GLUT5
      immunostaining was preferentially localized in the cytoplasm of alpha-cells
      compared to that of beta-cells. However, GLUT1 and GLUT4 were either barely or
      not at all detectable in any cells. These results suggest that rat islets take up
      glucose by at least three different processes and that blood glucose levels could
      be modulated differentially by: a high Km glucose transporter, GLUT2, in beta
      cells; by a low Km glucose transporter, GLUT3, in beta-cells; and by a low Km
      glucose transporter, GLUT5, in alpha-cells.

PMID- 9004534
TI  - An alternative pathway for clearance of dead lactotropes from rat pituitary
      gland.
AB  - In the pituitary glands of lactating rats there is a striking proliferation of
      lactotropes during pregnancy and lactation. After the cessation of lactation, the
      population of lactotropes experiences an extensive programmed cell death of
      redundant cells until it reaches prepregnancy levels. The regressive changes
      occurring in lactotropes are autolytic in nature and usually these cells are
      engulfed by stellate cells. Other involuting lactotropes are mobilized toward the
      blood capillaries and some go into the capillary lumen for final disposal,
      presumably in the mononuclear phagocyte system. In this study we report a
      sequence of events occurring in regressing lactotropes, investigated by a
      systematic electron microscope analysis of the rat pituitary gland at different
      periods after interruption of lactation. Direct disposal of degenerating
      lactotropes and their cell remnants appears to be an alternative pathway for the
      clearance of the regressing cells that occur extensively among surplus
      lactotropes following ablactation.

PMID- 9004535
TI  - The effects of dehydroepiandrosterone (DHEA) and its metabolites on the
      polycystic ovarian condition (PCO): cystogenic changes of rat granulosa cells in
      vitro.
AB  - During mammalian folliculogenesis, granulosa cells (GCs) are initially
      steroidogenically quiescent, later proliferate, and subsequently commence to
      hormonally differentiate, first producing estrogen and later, in the preovulatory
      stage, secreting both estrogen and progesterone. In this study and elsewhere, we
      have used follicle-stimulating hormone with a combination of growth factors in
      vitro to simulate the above in vivo conditions. In a previous study, we used
      dehydroepiandrosterone (DHEA) to accomplish the polycystic ovary condition (PCO)
      in rats. In the latter model, there were high circulating levels of DHEA and its
      metabolite, androstenedione. In the present study, we investigated the effects of
      high levels of DHEA (10(-5) M) and its metabolites, androstenedione,
      androstenediol and dehydroepiandrosterone sulfate on the quiescent,
      proliferative, and steroidogenically differentiating stages of GCs cultured in a
      serum-free medium for up to 10 days. In addition to possessing the regularly
      occurring organelles, when cultured with the aforementioned androgens, the GCs
      acquired endoplasmic reticulum of the smooth variety which is associated with
      steroidogenesis. The radioimmunoassay data showed that GCs cultured in the
      quiescent and proliferative stages in the presence of the androgens, no longer
      remain in these stages but proceed to differentiate in a preovulatory direction
      by producing both estrogen and progesterone. This study supports our hypothesis
      that high circulating levels of DHEA and/or its metabolites have most effect
      during the quiescent and proliferative stages of granulosa cells, with regard to
      their structure and their steroidogenic activities.

PMID- 9004536
TI  - Flow cytometric and ultrastructural aspects of the synergistic antitumor activity
      of vitamin C-vitamin K3 combinations against human prostatic carcinoma cells.
AB  - Transmission and scanning electron microscopy and flow cytometry were employed to
      characterize the cytotoxic effects of vitamin C (VC), vitamin K3 (VK3), or VC-VK3
      combinations on a human prostate carcinoma cell line (DU145) following a 1-h
      vitamin treatment and a 24-h incubation in culture medium. Cells exposed to VC
      exhibited membranous blebs, aberrant microvillar morphology, mitochondria with
      swollen cristae and intramitochondrial deposits, as well as nucleoli with
      segregated components. VK3-treated cells displayed a damaged cytoskeleton and
      membranes, a cytoplasm which contained large lumen, condensed polysomes, and
      severely damaged mitochondria with residual bodies, and nuclei which exhibited
      chromatic condensation, pyknosis, and karyolysis. VC-VK3-treated cells exhibited
      characteristics consistent with necrosis, i.e. swollen mitochondria and swollen,
      achromatic nuclei with marginated chromatin and intact envelopes, while other
      cells displayed characteristics consistent with apoptosis, i.e. expulsion of
      organelle-containing blebs, margination of nuclear chromatin, and segregation of
      nucleolar components. Vitamin treatment also decreased DNA synthesis, induced a
      S/G2 block in the cell cycle, and resulted in the accumulation of fragmented DNA.
      These results suggested that increased oxidative stress, subsequent membrane
      damage, and DNA fragmentation were responsible for enhanced cytotoxicity of the
      vitamin combination.

PMID- 9004537
TI  - Effects of exogenous growth hormone on skeletal muscle of young female rats.
AB  - We examined the effects of exogenous growth hormone (GH) treatment on the soleus
      and rectus femoris muscles of young female rats. Rat GH (1.8 IU/mg) was
      administered for 3 weeks by subcutaneous injection, twice a day, at doses of 0.5,
      0.6, and 0.8 mg/day during the 1st, 2nd and 3rd week, respectively. Final body
      weight, as well as wet and dry weight, of the soleus and rectus femoris muscles
      were significantly greater in the GH-treated group, compared to controls. Muscle
      weight to body weight ratios did not differ between the two groups. The fiber
      type composition of the soleus muscle was determined by histochemical staining
      for myosin ATPase activity. No statistically significant difference was found
      between the GH-treated and the control groups in the percentages of fiber types.
      However, GH treatment significantly increased the cross-sectional area of type II
      fibers of the soleus muscle. These results suggest that, in young female rats,
      acceleration of body weight gain by homologous GH administration is accompanied
      by a proportional hypertrophy of skeletal muscle mass. Increased muscle mass is
      due to hypertrophy of muscle fibers. Type II muscle fibers appear to be more
      sensitive to GH stimulation.

PMID- 9004540
TI  - Enhanced secretory ability for the human factor VIII light chain produced in
      baculovirus-infected insect cells.
AB  - The light and truncated heavy chains of human factor VIII, expressed separately
      in baculovirus-infected insect cells, exhibited different secretory behaviour
      when compared with each other and with a biologically active fusion molecule of
      the truncated heavy and light chains. The light chain was very efficiently
      secreted into culture medium, as judged by high extracellular protein levels and
      the absence of evidence for light chain retention within cells. Alternatively,
      proteins containing the heavy chain sequence were poorly secreted and appeared to
      be sequestered within cells, suggesting that regions within the heavy chain are
      responsible for the low levels of secreted protein which have generally been
      observed for recombinant factor VIII.

PMID- 9004539
TI  - Processing of mutated human proinsulin to mature insulin in the non-endocrine
      cell line, CHO.
AB  - Heterologous genes encoding proproteins, including proinsulin, generally produce
      mature protein when expressed in endocrine cells while unprocessed or partially
      processed protein is produced in non-endocrine cells. Proproteins, which are
      normally processed in the regulated pathway restricted to endocrine cells, do not
      always contain the recognition sequence for cleavage by furin, the endoprotease
      specific to the constitutive pathway, the principal protein processing pathway in
      non-endocrine cells. Human proinsulin consists of B-Chain-C-peptide-A-Chain and
      cleavage at the B/C and C/A junctions is required for processing. The B/C, but
      not the C/A junction, is recognised and cleaved in the constitute pathway. We
      expressed a human proinsulin and a mutated proinsulin gene with an engineered
      furin recognition sequence at the C/A junction and compared the processing
      efficiency of the mutant and native proinsulin in Chinese Hamster Ovary cells.
      The processing efficiency of the mutant proinsulin was 56% relative to 0.7% for
      native proinsulin. However, despite similar levels of mRNA being expressed in
      both cell lines, the absolute levels of immunoreactive insulin, normalized
      against mRNA levels, were 18-fold lower in the mutant proinsulin-expressing
      cells. As a result, there was only a marginal increase in absolute levels of
      insulin produced by these cells. This unexpected finding may result from
      preferential degradation of insulin in non-endocrine cells which lack the
      protection offered by the secretory granules found in endocrine cells.

PMID- 9004541
TI  - Danielone, a phytoalexin from papaya fruit.
AB  - A new phytoalexin was induced and isolated from papaya fruit slices treated with
      copper salts; its structure was established as 3',5'-dimethoxy-4'-hydroxy-(2
      hydroxy)acetophenone. This compound showed high antifungal activity against
      Colletotrichum gloesporioides, a pathogenic fungus of papaya.

PMID- 9004543
TI  - Biological activities of synthetic triterpenoid and steroid beta-D-xylopyranosyl
      (1-->6)-beta-D-glucopyranosides.
AB  - Comparisons of the activities of diosgenyl, methyl glycyrrhetinate or
      digitoxigenyl 3-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside with those
      of our previous glycosides supported our assumptions that both haemolytic and
      antifungal activities of steroid saponins are generally parallel to each other,
      while almost all haemolytic triterpenoid saponins show no antifungal activity,
      and that both antiviral and anti-ATPase activities of cardiac glycosides having a
      (1-->6) sugar linkage are much lower than those of the others.

PMID- 9004544
TI  - Steroidal glycosides from the underground parts of Hosta plantaginea var.
      japonica and their cytostatic activity on leukaemia HL-60 cells.
AB  - A new C22-steroid glycoside was isolated from the underground parts of Hosta
      plantaginea var. japonica, together with a known furostanol saponin and three
      known spirostanol saponins. The structure of the new steroid glycoside was
      characterized by spectroscopic analysis and acid-catalysed hydrolysis as 2 alpha,
      3 beta, 16 beta-trihydroxy-5 alpha-pregn-20(21)-ene-carboxylic acid gamma-lactone
      3-O-?O-beta-D-glucopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1--> 4)-beta-D
      galactopyranoside?. The isolated compounds were assayed for their cytostatic
      activity on leukaemia HL-60 cells. The spirostanol saponins showed cytostatic
      activity in a dose-dependent manner with the IC50 values ranging between 1 and 3
      micrograms ml-1.

PMID- 9004542
TI  - Biochemical activities of berberine, palmatine and sanguinarine mediating
      chemical defence against microorganisms and herbivores.
AB  - The alkaloids berberine, palmatine and sanguinarine are toxic to insects and
      vertebrates and inhibit the multiplication of bacteria, fungi and viruses.
      Biochemical properties which may contribute to these allelochemical activities
      were analysed. Acetylcholine esterase, butyrylcholinesterase, choline acetyl
      transferase, alpha 1- and alpha 2-adrenergic, nicotinergic, muscarinergic and
      serotonin2 receptors were substantially affected. Sanguinarine appears to be the
      most effective inhibitor of choline acetyl-transferase (IC50 284 nM), while the
      protoberberines were inactive at this target. Berberine and palmatine were most
      active at the alpha 2-receptor (binding with IC50 476 and 956 nM, respectively).
      Furthermore, berberine and sanguinarine intercalate DNA, inhibit DNA synthesis
      and reverse transcriptase. In addition, sanguinarine (but not berberine) affects
      membrane permeability and berberine protein biosynthesis. In consequence, these
      biochemical activities may mediate chemical defence against microorganisms,
      viruses and herbivores in the plants producing these alkaloids.

PMID- 9004545
TI  - Triterpenoid saponins from Anemone hupehensis.
AB  - Two new triterpenoid saponins, named hupehensis saponin F and G, were isolated
      from the water soluble part of Anemone hupehensis Lemoine. By chemical and
      spectroscopic evidence, their structures were elucidated as 3-O-beta-D
      ribopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1--> 2)-alpha-L-arabinopyranosyl
      hederagennin-28-O-alpha-rhamnopyranosyl(1--> 4)-beta-D-glucopyranosyl(1-->6)-beta
      D-glucopyranosyl(1--> 3)-alpha-L-rhamnopyranosyl(1-->4)-beta-glucopyranosyl(1-->
      6)-beta-D-glucopyranoside and 3-O-beta-D-ribopyranosyl(1-->3)-alpha-L
      rhamnopyranosyl(1--> 2)-alpha-L-arabinopyranosyl hederagenin-28-O-beta
      glucopyranosyl(1-->3)-alpha-rhamnopyranosyl( 1--> 4)-beta-D-glucopyranosyl(1-->6)
      beta-D-glucopyranosyl(1--> 3)-alpha-L-rhamnopyranosyl(1-->4)-beta-D
      glucopyranosyl(1--> 6)-beta-D-glucopyranoside, respectively.

PMID- 9004547
TI  - Processing in vitro of pronapin, the 2S storage-protein precursor of Brassica
      napus produced in a baculovirus expression system.
AB  - The maturation of the 2S albumin, napin, in Brassica napus L. involves removal of
      an amino-terminal and an internal propeptide. Pulse-chase experiments with B.
      napus embryos showed that intermediates are detectable during the pronapin
      processing. Intact pronapin was expressed by baculovirus in Spodoptera frugiperda
      insect cells in order to obtain substrate for studying the processing event.
      Processing of pronapin with a crude B. napus embryo protein extract resulted in
      several fragments of similar sizes to those of napin heavy and light chains. The
      character of the major processing activity in the B. napus extract suggested that
      it was due to an aspartic proteinase. A secondary activity indicated an
      additional endoproteinase involved in the pronapin processing. Limited
      proteolysis of pronapin with a purified aspartic proteinase from Hordeum vulgare
      showed that cleavage occurred exclusively in the prosequences. The cleavage
      products formed in-vitro requires additional trimming of the propeptides in order
      to obtain the subunits of mature napin.

PMID- 9004546
TI  - Triterpenoid saponins from Aster lingulatus.
AB  - Two new triterpenoid saponins named asterlingulatosides A and B were isolated
      from the whole plants of Aster lingulatus. Their structures were determined by
      spectroscopic data and chemical transformations to be 3-O-beta-D-glucopyranosyl-3
      beta,16 alpha-dihydroxyolean-12-en-28-oic acid-28-O-alpha-L-O-arabinopyranoside
      and 3-O-beta-D-glucopyranosyl-3 beta,16 alpha-dihydroxyolean-12-en-28-oic acid-28
      O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside++ +. They showed
      inhibitory activity on DNA synthesis in human leukaemia HL-60 cells.

PMID- 9004548
TI  - Changes in late-embryogenesis-abundant (LEA) messenger RNAs and dehydrins during
      maturation and premature drying of Ricinus communis L. seeds.
AB  - In Ricinus communis L. (castor bean) endosperms, two classes of Late
      Embryogenesis Abundant (Lea) transcripts were first detected during mid
      development (at 30-35 days after pollination, DAP) and peaked at 50 DAP, just
      prior to the onset of desiccation. Most of the Class I mRNAs declined
      substantially during desiccation itself; Class II mRNAs remained abundant in the
      mature dry (60 DAP) seed. Following imbibition, all Lea mRNAs abundant in the
      mature dry seed declined rapidly (within 5-24 h). Premature drying of developing
      35-DAP seeds resulted in the loss of storage-protein mRNAs (Leg B Mat I);
      following rehydration, mRNAs encoding post-germinative proteins (Germ D91, D30
      and D38) increased in the endosperm. The Lea mRNAs present in the developing
      fresh seed at 35 DAP were preserved, but did not increase in response to
      premature desiccation; upon rehydration these Lea mRNAs declined within 5 h.
      During seed development, substantial changes occurred in the synthesis of a
      subset of LEA proteins referred to as "dehydrins'; in particular, new dehydrin
      polypeptides were induced between 40 and 60 DAP. Such proteins were not as
      evident in prematurely dried endosperms. In contrast to the rapid loss of Lea
      mRNAs during germination, many of the dehydrin proteins abundant in the dried
      seed persisted following imbibition or rehydration.

PMID- 9004549
TI  - Purification and identification of apophycocyanin alpha and beta subunits from
      soluble protein extracts of the red alga Cyanidium caldarium. Light exposure is
      not a prerequisite for biosynthesis of the protein moiety of this photosynthetic
      accessory pigment.
AB  - Much controversy exists as to the level at which light exerts control over the
      biosynthesis of the photosynthetic apparatus in higher plants and other
      organisms. The eukaryotic red alga Cyanidium caldarium, like higher plants,
      undergoes light induction of chlorophyll synthesis. In addition to chlorophyll a
      the alga also synthesises the linear tetrapyrrole phycocyanobilin, which is
      combined with alpha or beta apobiliproteins to form phycocyanin, the major light
      harvesting pigment in this organism. We have previously shown that the
      tetrapyrrole precursor 5-aminolaevulinic acid (ALA) can substitute for light in
      inducing the biosynthesis of the phycocyanobilin moiety of this protein. We have
      also described the appearance of a protein of similar isoelectric point and
      molecular weight to phycocyanin in ALA-fed cells (Turner et al., 1992, Plant
      Physiol Biochem 30: 309-314). We now report on the protein's immunological and
      sequence identity with phycocyanin alpha and beta subunits, and provide further
      evidence that bilin-apoprotein ligation is light dependent.

PMID- 9004552
TI  - A pentapeptide model for an early folding step in the refolding of staphylococcal
      nuclease: the role of its turn propensity.
AB  - Recently the folding of a staphylococcal nuclease (P117G) variant was examined
      with the hydrogen-deuterium (H-D) exchange technique. Many of the residues that
      showed significant protection are located in beta-sheet regions. About half the
      residues protected belong to an antiparallel beta-hairpin structure (residues 21
      35) in the native structure. The beta-hairpin structure is formed by strands 2
      and 3 of sheet 2 connected by the sequence 27Y KGQP31 in a type 1' reverse turn
      conformation with a 4-->1 hydrogen bonding between Q30 NH and Y27 C = O. We have
      targeted the conformational characterization of the peptide model Ac-YKGQP-NH2
      with 1H two-dimensional nmr techniques in aqueous solution with a view to
      assessing its propensity to sample turn conformational forms and thus initiate
      the formation of beta-hairpin structure. Based upon the observed d alpha n (i, i
      + 1), d alpha n (i, i + 3), and dnn (i, i + 1) nuclear Overhauser effect
      connectivities, temperature coefficients for amide protons and conformational
      analysis with quantum mechanical perturbative configuration interaction over
      localized orbitals method, we conclude that the model peptide samples turn
      conformational forms with reduced conformational entropy. We suggest that the
      turn can nucleate the formation of the beta-hairpin structure in the refolding of
      nuclease. Observation of turn propensity for this sequence is consistent with the
      folding mechanism of the Greek key motif (present in Staphylococcal nuclease)
      proposed in the literature.

PMID- 9004551
TI  - Protein folding: optimized sequences obtained by simulated breeding in a
      minimalist model.
AB  - For a minimalist model of protein folding, which we introduced recently, we
      investigate various methods to obtain folding sequences. A detailed study of
      random sequences shows that, for this model, such sequences usually do not fold
      to their ground states during simulations. Straight-forward techniques for the
      construction of folding sequences, based solely on the target structure, fail. We
      describe in detail an optimization algorithm, based on genetic algorithms, for
      the "simulated breeding" of folding sequences in this model. We find that, for
      any target structure studied, there is not only a single folding sequence but a
      patch of sequences in sequence space that fold to this structure. In addition, we
      show that, much as in real proteins, nonhomologous sequences may fold to the same
      target structure.

PMID- 9004550
TI  - A two-dimensional NMR study of exchange behavior of amide hydrogens in a lysozyme
      derivative with an extra cross-link between Glu35 and Trp108--quenching of
      cooperative fluctuations and effects on the protein stability.
AB  - Two-dimensional nmr spectra [correlated spectroscopy (COSY), homonuclear Hartmann
      Hahn (HOHAHA), nuclear Overhauser effect spectroscopy (NOESY)] have been observed
      for cross-linked lysozyme, a chemically modified lysozyme derivative with an
      extra ester cross-link between residues E35 and W108. Eight shifted cross-peaks
      were found in the fingerprint region of COSY spectra. By searching COSY, HOHAHA
      and NOESY spectra, they have been assigned to A32, E35, S36, 158, A107, W108,
      V109, and A110. The NOE connectivities (dNN and d alpha N) found for the cross
      linked lysozyme are quite similar to those for the intact lysozyme. Exchange
      behavior of amide hydrogens has been studied for both intact and cross-linked
      lysozymes by observing the fingerprint region of COSY spectra. Hydrogen exchange
      reactions were carried out at pH 7.0 and at several temperatures. There exist 41
      amide hydrogens whose exchange reactions are detectable under this experimental
      condition. Not only exchange rates but also their activation enthalpies were
      determined for individual amide hydrogens. They are classified into two groups,
      which are called categories III and IV. Category III hydrogens are distributed in
      relatively flexible peripheral parts of protein, and category IV hydrogens are
      deeply buried in the core region of protein. Category III hydrogens are exchanged
      through localized unfolding around their sites with a low activation enthalpy
      ranging from 10 to 25 kcal/mol. The formation of an extra cross-link affects
      neither the exchange rate nor the activation enthalpy of category III hydrogens.
      However, amide hydrogens of residues 34-39 in the vicinity of the hinge are
      exceptions. They are easily exchanged in the intact lysozyme but their exchange
      rates are drastically retarded by cross-linking. In the intact lysozyme,
      structural fluctuations mediating the exchange of category IV hydrogens are
      highly cooperative with a large activation enthalpy. These large-scale structural
      fluctuations are the global unfolding of the overall structure and also concerted
      motions within a domain. Especially near 38 degrees C, it was found that the
      dominant fluctuation occurring in the alpha-domain is different from that in the
      beta-domain. However, these concerted motions are strongly quenched by the
      formation of the cross-link because of the cooperativity of such a large-scale
      fluctuation. The stabilization of a localized area of protein by cross-linking
      results in the great suppression of large-scale and concerted motions. The
      exchange rates of category IV hydrogens are extremely retarded in the cross
      linked lysozyme, so that they are exchanged through the so-called penetration
      mechanism characterized by a low activation enthalpy. These experimental results
      are discussed with regard to the contribution of cross-linking to the
      stabilization of the folded structure of protein.

PMID- 9004553
TI  - A new approach to secondary structure evaluation: secondary structure prediction
      of porcine adenylate kinase and yeast guanylate kinase by CD spectroscopy of
      overlapping synthetic peptide segments.
AB  - A new approach for evaluating the secondary structure of proteins by CD
      spectroscopy of overlapping peptide segments is applied to porcine adenylate
      kinase (AK1) and yeast guanylate kinase (GK3). One hundred seventy-six peptide
      segments of a length of 15 residues, overlapping by 13 residues and covering the
      complete sequences of AK1 and GK3, were synthesized in order to evaluate their
      secondary structure composition by CD spectroscopy. The peptides were prepared by
      solid phase multiple peptide synthesis method using the 9
      fluorenylmethoxycarbonyl/tert-butyl strategy. The individual peptide secondary
      structures were studied with CD spectroscopy in a mixture of 30% trifluoroethanol
      in phosphate buffer (pH 7) and subsequently compared with x-ray data of AK1 and
      GK3. Peptide segments that cover alpha-helical regions of the AK1 or GK3 sequence
      mainly showed CD spectra with increasing and decreasing Cotton effects that were
      typical for appearing and disappearing alpha-helical structures. For segments
      with dominating beta-sheet conformation, however, the application of this method
      is limited due to the stability and clustering of beta-sheet segments in solution
      and due to the difficult interpretation of random-coiled superimposed beta-sheet
      CD signals. Nevertheless, the results of this method especially for alpha-helical
      segments are very impressive. All alpha-helical and 71% of the beta-sheet
      containing regions of the AK1 and GK3 could be identified. Moreover, it was shown
      that CD spectra of consecutive peptide content reveal the appearance and
      disappearance of alpha-helical secondary structure elements and help localizing
      them on the sequence string.

PMID- 9004554
TI  - Stabilization of the B conformation in unoriented films of calf thymus DNA by
      NaCl: a Raman and IR study.
AB  - Unoriented films of calf thymus NaDNA with either 3.0 or 5.0 NaCl per base pair
      were prepared by dehydrating unstressed gels. These films were studied by Raman
      and ir spectroscopy. The 5.0 samples showed very strong vibrational modes
      characteristic of the B conformation at relative humidities (RH) as low as 30%,
      indicating that those samples were entirely in the B conformation. The 3.0
      samples showed weaker features: some of the DNA in these samples were in the B
      conformation at 80% RH while the DNA is essentially in a disordered phase at 30%
      RH.

PMID- 9004556
TI  - Phylogenetic relationships among turbellarian orders inferred from 18S rDNA
      sequences.
AB  - The turbellarian flatworm is a key group to understand the origin and the early
      evolution of triploblastic, bilaterally symmetrical animals, but phylogenetic
      relationships among turbellarian orders have been a subject of debates for
      decades, especially on the position of the acoel turbellarians. Some workers have
      considered the acoel representing the most primitive turbellarian order but
      others have regarded them as regressive. We determined almost the entire lengths
      of the nucleotide sequences of 18S ribosomal RNA gene (rDNA) in 17 species from 9
      turbellarian orders (the Acoela, Catenulida, Macrostomida, Lecithoepitheliata,
      Rhabdocoela, Prolecithophora, Proseriata, Tricladida, and Polycladida). After
      adding the sequences of a cestode, two trematodes and some diploblastic animals
      obtained from databases, we reconstructed phylogenetic trees using the neighbor
      joining, maximum-likelihood and maximum-parsimony methods. All trees
      significantly indicated that the Acoela is the earliest divergent group among the
      turbellarian orders. The trees also suggested that the Tricladida evolved in the
      separate lineage from that of a cluster of the Catenulida, Macrostomida,
      Lecithoepitheliata, Rhabdocoela, Polycladida, Trematoda and Cestoda after the
      divergence of the Acoela.

PMID- 9004557
TI  - Lack of leadership over advanced practice.

PMID- 9004558
TI  - Should the NHS take over prison services?

PMID- 9004555
TI  - The mRNA expression of neurocan, a brain-specific chondroitin sulfate
      proteoglycan, in neoplastic mammary glands in mice.
AB  - In the experiment of mouse transforming growth factor alpha (TGF alpha) gene
      expression in mammary tumors, various sizes of amplified products by reverse
      transcriptase-polymerase chain reaction (RT-PCR) using mouse TGF alpha primers
      were detected in addition to a predicted size in four strains of mice. During the
      further analysis of these RT-PCR products in mouse mammary tumors, the transcript
      of neurocan gene was detected in the mammary tumor from SHN mice by the cloning
      and nucleotide sequence analysis after RT-PCR reaction using mouse TGF alpha
      primers. The 5'-nucleotide sequence of sequential 246bp in the amplified cDNA of
      527bp was completely identical to a middle part of mouse neurocan cDNA sequence,
      one of the chondroitin-sulfate proteoglycan expressed in the nervous tissue.

PMID- 9004559
TI  - Pressure sore management in the independent sector: 2.
AB  - This is the second of two articles looking at pressure sore prevention and
      treatment in the independent sector of a large northern city. Part one presented
      background information, details of data collection and analysis, baseline data on
      current practice and initial conclusions which included an assessment of the
      extent of evidence-based practice, equipment use, educational needs, patient and
      informal carer involvement and quality of care maintenance. Part two considers
      these findings in greater depth. Both positive and negative aspects of pressure
      sore management in the independent sector are explored. Factors such as the
      number and types of pressure-relieving equipment used and the lack of independent
      evidence regarding product efficacy are considered. The survey highlights gaps in
      educational provision, and the lack of research evidence on certain aspects of
      care. The article concludes with a detailed series of recommendations with regard
      to practice, education and research.

PMID- 9004560
TI  - Port wine stains: laser treatment and nursing management.
AB  - In 1960, an American physicist Theodore Maiman observed the first laser in
      action. Since then laser technology has progressed at an extraordinary rate. This
      article shows how one type of laser has touched the lives of thousands of people.
      The Candela tunable dye laser has given hope to people with port wine stain
      birthmarks. It also shows the duties and responsibilities of the nurse working
      with lasers and the possibility of the extended role of the nurse in the field of
      skin laser therapy.

PMID- 9004561
TI  - Community assessment of a patient following hip replacement.

PMID- 9004562
TI  - Aging and quality of life. 1: Towards a better understanding.
AB  - This article, the first in a two-part series, considers a number of factors that
      influence quality of life in older age. It highlights the tensions between
      objective and subjective dimensions regarding the quality of life. It emphasizes
      the differences between those definitions used by professionals and those
      employed by older people themselves. The authors argue that there is a need to
      gain a broader understanding of how people adjust to and interpret their own
      ageing before the appropriate services can be designed. Assimilation,
      accommodation and immunization are presented as useful concepts to improve
      understanding in this important area.

PMID- 9004563
TI  - The causes and nursing management of constipation.
AB  - Constipation is a common symptom in the Western world with up to 10% of the
      population experiencing some difficulty with bowel evacuation. The consequences
      are seldom serious or life-threatening, but constipation is undoubtedly the cause
      of much chronic discomfort and misery. Most nurses will encounter constipated
      patients on a regular basis. It is therefore important for nurses to understand
      the causes of constipation so that an appropriate history can be taken and
      further investigations suggested if necessary.

PMID- 9004565
TI  - Relevance of the nature vs nurture debate to clinical nursing.
AB  - The philosophy of holistic care underpins nurse education, and the 'nature
      nurture debate' is frequently used to facilitate discussion regarding the
      influence of interactions with the environment in 'shaping' the individual. A
      limitation to this approach is that much of the work cited in the literature
      relates primarily to psychosocial interactions. This conveys a narrow perspective
      on holism, and creates an impression that the debate cannot be applied to other
      aspects of health and wellbeing, yet models of nursing care emphasize the need
      for nurses to appreciate the interactional basis of health. This article uses
      examples from mental health, physical health and the influence of ageing, to
      argue that interactions must be viewed from a much wider perspective. Only in
      doing so can the principles and application of holistic care, and an
      understanding of the bases of health education practices, be appreciated.

PMID- 9004564
TI  - Care of a patient with post-traumatic stress disorder.

PMID- 9004566
TI  - Tegasorb hydrocolloid dressing: advanced formulation.
AB  - Tegasorb advanced formulation hydrocolloid dressing from 3M Healthcare can be
      used on a variety of wounds, e.g. leg ulcers and donor sites. It encourages a
      moist wound-healing environment and can be used in all stages of wound healing,
      from black necrotic tissue to the epithelializing wound. Tegasorb is a well
      established hydrocolloid dressing that has recently been relaunched as an
      advanced formulation.

PMID- 9004567
TI  - Nurses' role in peripheral venous cannulation.

PMID- 9004568
TI  - Family participation in hospice home care.

PMID- 9004569
TI  - Advocacy: the cornerstone of cancer survivorship.
AB  - PURPOSE: This article describes a cancer-related advocacy skill set that can be
      acquired through a learning process. OVERVIEW: Cancer survivorship is a process
      rather than a stage or time point, and it involves a continuum of events from
      diagnosis onward. There exists little consensus about what underlying processes
      explain different levels of long term functioning, but skills necessary for
      positive adaptation to cancer have been identified from both the professional
      literature and from the rich experiences of cancer survivors. CLINICAL
      IMPLICATIONS: Healthcare practitioners need to be more creative and assertive in
      fostering consumer empowerment and should incorporate advocacy training into care
      plans. Strategies that emphasize personal competency and increase self-advocacy
      capabilities enable patients to make the best possible decisions for themselves
      regarding their cancer care. In addition, oncology practitioners must become
      informed advocacy partners with their patients in the public debate about
      healthcare and cancer care delivery.

PMID- 9004570
TI  - Burden of care and lung cancer.
AB  - PURPOSE: Although direct costs for treatment are important considerations in
      healthcare planning, the indirect costs of chronic care may have an even more
      profound impact on families. The burden of care of chronic illnesses is seldom
      addressed in healthcare policies. This article uses lung cancer as a model to
      illustrate the burden of care of chronic illness and to examine the many
      healthcare problems that affect patients, families, and society at large.
      OVERVIEW: Lung cancer, as a major cause of morbidity and mortality, and the
      second most expensive cost of cancer care, will impact more than 1 million
      Americans and their families in the next decade. In this article, a health
      services model is used to address burden of care for people with lung cancer.
      Predisposing factors, enabling factors, and need for healthcare are considered.
      Lung cancer literature related to emotional status, functional status, and
      symptom distress are reviewed as they relate to the physical, emotional, and
      social aspects of the burden of care. CLINICAL IMPLICATIONS: The increasing
      responsibilities of the family in providing care in the face of limited external
      support, and the consequences of that caregiving, for the patient and family,
      raise serious concerns for clinicians. With quality of life as the ultimate
      health outcome, clinicians are challenged to contribute to a research and policy
      agenda that addresses burden of care.

PMID- 9004572
TI  - Psychosocial stresses and adjustment of nasopharyngeal carcinoma patients in Hong
      Kong: a panel study.
AB  - PURPOSE: This article reports the results of a study conducted in Hong Kong from
      November 1992 to May 1994 on patients with nasopharyngeal carcinoma. The
      objective was to understand stresses and the short-term psychosocial adjustment
      outcome throughout the course of the illness. DESCRIPTION OF STUDY: A cognitive
      appraisal model of stress was used, and short-term psychosocial adjustment
      outcome was measured by psychological distress, social maladjustment to illness,
      and health status as perceived by the patients and as viewed by the oncologist. A
      panel study was adopted as the research design. A total of 125 patients were
      interviewed in the diagnostic phase, dropping to 119 in the treatment phase and
      111 in the post-treatment phase. Data were gathered through face-to-face
      interviews by a structured instrument, the reliability of which had been
      evaluated immediately before the start of the study. RESULTS: The patients' level
      of anxiety was highest in the diagnostic phase, and gradually declined in the
      treatment and the post-treatment phases. Level of depression remained unchanged
      in the diagnostic and treatment phases, and decreased in the post-treatment
      phase; social maladjustment to illness and health status were poorest in the
      treatment phase. CLINICAL IMPLICATIONS: Health professionals can sharpen the
      focus of their work by helping nasopharyngeal carcinoma patients to lower their
      psychological distress in the diagnostic phase, enhance their social functioning,
      and improve their health status in the treatment and the post-treatment phases.

PMID- 9004571
TI  - Natural killer cells over time in patients with colorectal cancer.
AB  - PURPOSE: The purposes of the investigation were: 1) to examine the natural killer
      (NK) cell levels in a homogeneous group of patients with cancer between the
      presurgical period and 6 months after surgery; 2) to identify changes in the
      number of NK cells over time; and 3) to determine whether an association exists
      among the number of NK cells, demographics, stage of cancer, and treatment
      variables. DESCRIPTION OF STUDY: A longitudinal descriptive design was used to
      study biopsychosocial factors in persons newly diagnosed with colorectal cancer
      over a 6-month period. RESULTS: Patients without ostomies had a significant
      decrease in NK levels over time, whereas patients with ostomies had a significant
      increase in NK levels over time. There was a difference in NK level over time for
      patients who were receiving the additional therapy of radiation alone and a
      combination of radiation and chemotherapy from those patients who were not
      receiving additional therapy. Natural killer levels in patients who were
      receiving radiation alone or a combination of radiation and chemotherapy
      significantly declined over time, where NK levels in patients receiving no
      additional treatment significantly increased over time. CLINICAL IMPLICATIONS:
      Patients with low NK levels should be monitored during the course of their
      illness and cancer treatment to determine the relationship to immune status of
      other variables such as nutritional status, infection rates, and functional
      status.

PMID- 9004573
TI  - Challenges to behavioral research in oncology.
AB  - PURPOSE: The difficulties encountered by investigators in conducting behavioral
      research with oncology patients have received little attention in the literature.
      This article provides a practical guide to problems that might be anticipated in
      the planning and conduct of behavioral research. OVERVIEW: Problems include
      subject accrual and retention, development of a multidisciplinary research team,
      control of confounding variables, psychosocial instrumentation issues, and
      acceptance of the need for behavioral research. Methodological and feasibility
      issues are examined. Strategies for addressing the issues are presented. CLINICAL
      IMPLICATIONS: Successful behavioral research in oncology requires firm grounding
      in clinical practice. Clinicians can improve the quality of research and thus,
      the scientific base for practice by joining or facilitating multidisciplinary
      research efforts.

PMID- 9004574
TI  - Side effects burden in women with breast cancer.
AB  - PURPOSE: This article describes the side effects burden of 307 women who were
      receiving treatment for breast cancer. The study provides a description of the
      impact of side effects burden on adult role activities (self-help), self-care,
      psychological adjustment, and quality of life. DESCRIPTION OF STUDY: Data to
      describe the side effects burden characteristics of 307 women receiving treatment
      for breast cancer were drawn from the Self-Help Intervention Project. Data were
      collected after medical treatment was underway and treatment-related side effects
      were evidenced. The impact of side effects burden on adult role activities (self
      help), self-care, psychological adjustment, and life quality is described.
      RESULTS: Fatigue was the most common side effect as well as the most problematic.
      Number of side effects and increase in side effects were moderately correlated (P
      < 0.0001) in a negative direction with fatigue and depression. Self-care
      behaviors also were associated negatively with the extension of side effects and
      with fatigue and depression (P < 0.001). Psychological adjustment was associated
      with difficulty sleeping, anxiety, and depression. Overall life quality was noted
      to be negatively related to depression as was present life quality. CLINICAL
      IMPLICATIONS: Data support the need for clinical interventions that are
      individualized to women's side effects experience. Additional research is
      underway to test the effectiveness of the interventions specified by the overall
      study.

PMID- 9004575
TI  - Sources of information about consent in cancer research.

PMID- 9004576
TI  - Collaborative role of a nurse practitioner in a university radiation oncology
      department.

PMID- 9004578
TI  - Provincial Immunization and Communicable Disease Information System coming on
      line.

PMID- 9004577
TI  - Liposomal doxorubicin.

PMID- 9004582
TI  - Eavesdropping on our neighbors to the North.

PMID- 9004581
TI  - Health renewal achieves goals.

PMID- 9004583
TI  - Protocol for prevention of complications of endotracheal intubation.

PMID- 9004584
TI  - Protocol for prevention of complications of endotracheal intubation.

PMID- 9004585
TI  - Interleukin-2 therapy for renal cell cancer: indications, effects, and nursing
      implications.

PMID- 9004587
TI  - Managing aortic dissections: a critical care challenge.

PMID- 9004588
TI  - High-Tech home care: an expanding critical care frontier.

PMID- 9004589
TI  - The pathophysiology of potassium balance.
AB  - Knowledge of the mechanisms causing potassium imbalance provides tools for the
      nurse to assess symptoms and intervene with appropriate and timely action for
      patients with potassium imbalance. Figure 5 provides a flow chart as a guide for
      carrying out assessment of potassium balance in those individuals who are at
      risk.

PMID- 9004586
TI  - Continuous arteriovenous hemofiltration: a case study.

PMID- 9004590
TI  - Laboratory analysis.

PMID- 9004591
TI  - Patient care conference: a coordinated, collaborative effort.
AB  - The flow chart, guidelines, and document describe the mechanism for patient care
      conferences. Because the need, process, and documentation of patient care
      conferences have been clarified, care conferences are now more consistent,
      efficient, and effective. Documentation streamlined the process of setting up
      care conferences by recording the following information: who was notified, who
      would attend, specific issues to be discussed, conference scheduling summary of
      plans and decisions made. Task force satisfaction was high because of a short
      timeline, clear problem definition, clear goals, team sponsorship, and a good end
      product. Use of continuous quality improvement techniques added to the success of
      this project, because there was a methodology for starting with a variable,
      unclear process and ending with a creative, efficient process. All members of the
      healthcare team and patients and families were satisfied, because the patient
      care conference was available to discuss specific issues and reach consensus on
      decisions about the patient's treatment plan at critical points during the
      patient's hospital course.

PMID- 9004592
TI  - Acute renal failure in the newborn.
AB  - Newborns at risk for acute renal failure require immediate diagnosis and
      treatment. Supportive care must be provided while the kidney heals and begins
      functioning again. The critical care nurse plays a vital role in early
      recognition and treatment of signs and symptoms of acute renal failure. As
      technology improves, a greater number of acutely ill newborns are surviving. The
      critical care nurse is managing more neonates with acute renal failure. Expertise
      in caring for these infants has also improved. Quality nursing care plays a
      crucial role in preventing complications and improving the prognosis of neonates
      with renal failure.

PMID- 9004593
TI  - Management of genetic information: professional and ethical challenges in
      nursing. Interview by Michael Villaire.

PMID- 9004594
TI  - Are dedicated monitor watchers necessary on a telemetry unit?

PMID- 9004595
TI  - Resolution or consequence?

PMID- 9004596
TI  - Gifts that only you can give.

PMID- 9004597
TI  - Removal of femoral sheaths by registered nurses.

PMID- 9004599
TI  - Decompression sickness and decompression air embolism: treatment with hyperbaric
      oxygen and nursing management.

PMID- 9004598
TI  - Intracoronary urokinase for restoring circulation in occluded saphenous vein
      grafts.

PMID- 9004600
TI  - Gastric tonometry: evaluating tissue oxygenation.
AB  - Critically ill patients require vigilant monitoring of tissue oxygenation,
      particularly oxygenation of the gut mucosa, because of the mucosa's fragile blood
      supply. With the advent of gastric tonometry, splanchnic tissue oxygenation can
      be measured in a minimally invasive and cost-effective manner. Requiring only a
      gastric tonometer (approximately $70) and facilities to measure arterial blood
      gases, this method allows early detection of covert compensated shock by
      determining pHi. Thus, early intervention and correction of deficits in tissue
      oxygenation are possible and may improve patients' outcome.

PMID- 9004601
TI  - ST-T segment changes in a patient with ECG evidence that suggests stenosis of the
      proximal left anterior descending artery.

PMID- 9004602
TI  - Case management of patients with chronic critical illness.

PMID- 9004603
TI  - Preoperative antioxidant and allopurinol therapy for reducing reperfusion-induced
      injury in patients undergoing cardiothoracic surgery.
AB  - Administration of vitamin E, vitamin C, and allopurinol to reduce reperfusion
      induced injury remains controversial. Clinical trials are being conducted, and
      the results are promising. No adverse side effects have been reported with the
      short-term use of these drugs. The cost of the pre-operative medication is
      approximately $5 per week, which favors its use. The ability of nurses to be
      effective advocates of patients receiving these drugs is vital. What appears to
      be a trivial medication regimen may save myocardial cells and promote an
      uncomplicated postoperative period.

PMID- 9004604
TI  - Academic education. Creating a laboratory that simulates the critical care
      environment.
AB  - Educating students and practicing nurses for the complexities and demands of
      critical care is a challenge. Training in a laboratory that simulates the
      critical care setting is an excellent teaching method that can be used to
      supplement lectures and clinical experiences. Developing such a laboratory is an
      exciting and rewarding process that will promote learning and ultimately benefit
      the care of critically ill patients.

PMID- 9004605
TI  - Management. The challenge to define progressive care units.

PMID- 9004607
TI  - The Patient Self-Determination Act: helping people confront end-of-life care
      issues before emergency strikes. Interview by Marilyn Petterson.

PMID- 9004608
TI  - Where should the transducer be leveled for radial or femoral arterial pressure
      monitoring?

PMID- 9004606
TI  - Pediatric. Tolerance, dependence, and strategies for compassionate withdrawal of
      analgesics and anxiolytics in the pediatric ICU.

PMID- 9004609
TI  - Nursing unites around action initiatives.

PMID- 9004610
TI  - 85th Annual FNA Convention. Keynote Address.

PMID- 9004611
TI  - Knowing your workplace rights.

PMID- 9004612
TI  - Nurse practitioner week is coming, plan for it now.

PMID- 9004613
TI  - The legal regulation of nursing practice.

PMID- 9004614
TI  - Professional regulation: the profession governing itself.

PMID- 9004615
TI  - Leaders building leaders.

PMID- 9004616
TI  - Through the eyes of a student. Where is my yellow brick road leading me?

PMID- 9004617
TI  - FNSA nurse staffing report.

PMID- 9004618
TI  - New managed care legislation--what does it all mean, anyway?

PMID- 9004619
TI  - Delegation of medication administration?

PMID- 9004620
TI  - Psychobiology and psychodynamics in nursing in the UK and US.

PMID- 9004621
TI  - An extended literature review of health professionals' perceptions of illicit
      drugs and their clients who use them.
AB  - The literature relating to health professionals and illicit drugs and clients who
      use them shows many common themes. It is evident that the majority of health
      professionals hold negative, stereotypical perceptions of illicit drug-users.
      Consequently, these negative attitudes become prejudicial, hence blocking the
      professional from carrying out effective and humane nursing care to this client
      group. Evidence also shows that health professionals' perceptions on the
      legalization of currently illicit drugs is linked to their own use of these drugs
      rather than any social or health reasons. Professionals' views on the different
      illicit substances are also coloured by their use, not by the actual evidence
      relating to the effects of that drug, in particular, cannabis. The literature
      shows that health professionals project heavily on to the client all their own
      negative perceptions of illicit drug use, in the care setting. This has produced
      very unsatisfactory and unsafe care, resulting in both client and carer being
      dissatisfied with the whole aspect of care. In addition, specialist teams are
      being swamped by health professionals who are referring almost every illicit drug
      user to these services. The future may be brighter with the generalist and
      specialist working closely together for the benefit of all, especially the client
      and, ultimately, the community.

PMID- 9004623
TI  - The self-management of psychiatric medications: a pilot study.
AB  - This paper reports on a pilot study where a scheme for the self-management of
      medication has been devised as an intervention strategy, where the mental health
      nurse and the mentally ill client work together to improve the client's knowledge
      of prescribed medication and medication-related issues. Aspects of non-compliance
      and the various factors involved in the non-compliance of psychiatric medications
      by the person who is severely mentally ill are discussed. When non-compliance to
      psychiatric medication is briefly examined, the complexity of the phenomena
      becomes increasingly apparent, confounding single intervention strategies,
      therefore as the phenomena is multidimensional, so must by any response. A review
      of the literature, and from the past clinical experience of the authors, suggests
      that when there is an involved therapeutic alliance, and the active participation
      of both the client and the mental health nurse in a rehabilitation orientated
      self-medication management scheme, a difference can occur for the client where
      their understanding of, and compliance with, psychiatric medication can improve.
      This could possibly improve the overall quality of life for the mentally ill
      person. Within a psychosocial rehabilitation setting, a self-medication
      management scheme has been developed that gradually facilitates the client's
      responsibility for managing their own prescribed medication, and in conjunction
      with this increased awareness of their medication and related issues, the focus
      eventually leads to the client having complete responsibility for managing their
      own medication. This self-medication management scheme consists of several graded
      stages that are contractual in nature, in which the clients and nurses are active
      participants. A rating and self-reporting scale has been developed within the
      scheme and is used by both the nurse and the client to assist in gauging the
      client's understanding and knowledge of issues related to their medication use.
      This self-medication management scheme has demonstrated that when severely
      mentally ill persons are given the opportunity to practice and manage their own
      medication as a component of the rehabilitative process, a self-medication
      management scheme does make a difference.

PMID- 9004624
TI  - Scatolia: psychosis to protest.
AB  - This paper presents the case of a female patient in a special hospital who
      engaged in faecal smearing whilst in seclusion. A management investigation
      followed a complaint by a Nurse Manager regarding the reluctance of staff to
      clean the room whilst the patients remained disturbed. The investigation team
      adopted a triangulated method of interviews, literature review, survey and case
      presentations to study the issues involved. The results presented here suggest
      the emergence of similar issues from both the interview commentary and the
      tabulated data from the survey. There appears an intricate and complex dilemma
      facing those managing situations involving scatolic behaviour. There are issues
      of concern from diverse organizational settings that overlap between those
      persons who engage in scatolia who may be deemed mentally impaired,
      psychiatrically disordered, or protest behaviour.

PMID- 9004622
TI  - Recovering from depression: a one-year follow-up.
AB  - The purpose of this research was to further describe the process of recovering in
      women who have been depressed. In prior research, recovering from depression
      consisted of eight categories within three distinct phases and was initiated by a
      crisis or 'Turning Point' experience. In-depth follow-up interviews with the
      seven women who participated in a study that had been performed one year earlier
      were conducted in order to: (i) determine their status in the recovering process;
      (ii) describe in greater depth the antecedents of the recovering process; (iii)
      identify potential interventions to assist women in recovering. No new phases of
      the recovering process were identified in the present study. Interventions that
      assisted recovering were psychoeducational in nature, instilled hope, and
      provided for individualized treatment. Recommendations for further research are
      included in this study. Little empirically based information is available on the
      process or recovering among women who experience depression. This research is a
      one-year follow-up of women who participated in an earlier qualitative study of
      the process of recovering in women who had been depressed. In the previous study,
      recovering from depression was found to consist of eight categories within three
      distinct phases, and to be initiated by a crisis or Turning Point experience. The
      purpose of this present study were to: (i) determine the status of the recovering
      process one year later; (ii) more fully describe the antecedents of the process;
      and (iii) propose testable nursing interventions to assist women with depression
      toward recovering.

PMID- 9004625
TI  - The role of empathy in the care of dementia.
AB  - The concept of empathy in relation to caring is reviewed. A variety of
      definitions of empathy are considered to show how empathy has been used within
      general nursing practice. A wide range of literature is drawn on to gain insights
      into the multifaceted and diverse information on this topic. The differing
      perceptions that arise from various professional viewpoints are explored. A set
      of attributes are identified for empathy and these are considered in relation to
      clinical practice in elderly mental health. Three examples of care are discussed
      to show how emotive empathy can be employed to give an improved direction to care
      of dementia clients. The concept is reviewed in relation to the particular needs
      of caring for dementia. It is suggested that it should be included in mental
      health training. It is concluded that emotive empathy has a vital part to play in
      the delivery of care for the elderly mentally ill.

PMID- 9004626
TI  - Therapeutic interventions associated with seclusion of acutely disturbed
      individuals.
AB  - The use of seclusion--i.e. placing an individual in a specially designed room
      with a locked door--continues to be an option in the management of mentally ill
      individuals whose behaviour is acutely disturbed, and who pose a personal and/or
      environmental threat. In a grounded theory study of psychiatric nurses' use of
      seclusion in two closed wards in a metropolitan teaching hospital in Australia,
      'intervening' and 'mainstreaming' are the categories that describe nursing
      interventions developed from constant comparison of the data collected. Details
      of these interventions are presented, with reference to the skills that
      participants describe as necessary in the care of a mentally ill patient being
      secluded and then being re-integrated into ward life. Considerations for further
      study on the topic of seclusion are presented.

PMID- 9004627
TI  - Substance abuse.

PMID- 9004628
TI  - Discharge planning--Leanchoil Hospital.

PMID- 9004629
TI  - Rehabilitation--functional independence measure.

PMID- 9004630
TI  - Dementia care planning--Highland.

PMID- 9004631
TI  - What to do with psychiatric nursing?

PMID- 9004632
TI  - Nurses who work with mentally disordered people should be appropriately
      qualified.

PMID- 9004634
TI  - Group processes in a case discussion workshop for community psychiatric nurses.
AB  - This paper describes a case discussion workshop with a team of hospital-based
      community psychiatric nurses (CPNs). After describing the growth of the CPN
      movement in Britain and the conflicting ideas surrounding the professional role
      of CPNs, some of the group processes within a particular group of CPNs will be
      illustrated. Particular attention is paid to the way in which reading material
      distributed to the group may reflect group processes, and the way in which
      institutional factors impinge on case discussions. The case for various forms of
      psychodynamic input into community psychiatric teams is also made.

PMID- 9004633
TI  - Pathological gambling: a review of the literature.
AB  - Most national surveys into gambling have concluded that there are more gamblers
      than non-gamblers. Although most gamblers can control their gambling behaviour, a
      small minority can suffer from pathological gambling. The acquisition,
      development and maintenance of pathological gambling is an area that is
      continually disputed and was only recognized as a bona fide mental disorder in
      the third edition of the Diagnostic and Statistical Manual (DSM-III, American
      Psychiatric Association 1980). The exact causes and reasons for continuing
      gambling behaviour seem to be dependent upon the individual, but there does seem
      to be some general underlying factors and reoccurring themes. This paper reviews
      the prevalence and history of pathological gambling and traces the phases of the
      pathological gambler's career. It is concluded that explanations of gambling
      behaviour (and particularly excessive gambling) are best served by an integrated
      biopsychosocial model, which stresses the individuality and idiosyncratic nature
      of the development of gambling problems.

PMID- 9004635
TI  - The psychiatric patient's right to self-determination: a preliminary
      investigation from the professional nurse's point of view.
AB  - The aim of this preliminary empirical investigation was to explore the concept of
      self-determination and to discuss its applicability to psychiatric nursing. The
      data were collected with a questionnaire submitted to professional nurses (n =
      127) working on the long-term wards in four Finnish hospitals. Data analysis
      combined the methods of content analysis and quantitative statistics. A tentative
      concept apparatus was created in order to provide nursing science with a broader
      understanding of the issue at hand. Nurses identified various factors that act to
      restrict and to support self-determination: the most common restrictive factor
      was the patient's illness or condition, and the most common supportive factor was
      nursing intervention. Views differed on the importance of self-determination in
      the case of psychiatric patients; over half of the nurses described the right to
      self-determination as very important. On the basis of the findings it is
      concluded that self-determination is a valid concept for the psychiatric patient.
      It was also thought to serve the needs of education as well as evaluation.

PMID- 9004637
TI  - User involvement in mental health nursing practice: rhetoric or reality?
AB  - Following the review of mental health nursing, nurses need to address the dilemma
      for providing empowering care in a climate of increasing control and stigma. This
      paper discusses the background to, and significance for nursing, of the 'user
      movement' in the UK. A current 'explosion' of user groups does not imply that
      these form a homogeneous group, nor that they share similar perspectives.
      Consultation and involvement mean little if unmatched with action. This may be
      constrained by the 'market' in which the 'true power' is held by the budget
      holder, and by stigmatizing policy imperatives claimed to be in the public
      interest. Self-advocacy may be legitimized by the desire to prevent providers
      'speaking out'. These difficulties may, however, provide convenient excuses for
      inaction. A new professional identity may be found in forging political alliances
      with users, in which a reappraisal of traditional boundaries may go some way
      towards reducing the stigma surrounding mental health problems.

PMID- 9004636
TI  - Life after the mental hospital: the way of life of deinstitutionalized
      psychiatric patients.
AB  - This article describes and analyses the way of life of deinstitutionalized long
      term psychiatric patients in Northern Finland. The major focus of the paper is
      the central areas of life of the outpatients as one dimension of subjectivity.
      The data were collected by interviewing 25 discharged long-term psychiatric
      patients. The findings suggest that home was the central area of life for the
      outpatients but they differed in their relation to it. Some of the patients were
      actively building their home. For some others home was an asylum in which to hide
      from social life. Many patients had hobbies that only took place inside their
      homes. One of the problems that the outpatients had to face was lack of work. The
      elderly patients who generally regarded work as a virtue experienced difficulties
      in finding something to do in their modern suburban homes. Social participation
      was mostly labelled by the old and familiar hospital models. The patients had no
      new acquaintances. They kept contact with their former fellow patients.

PMID- 9004638
TI  - Empowering service users: the myth, the reality and the hope.

PMID- 9004640
TI  - Career options--the increasing demand for courtroom nurses.

PMID- 9004639
TI  - Changing roles: the impact of multiple sclerosis.

PMID- 9004641
TI  - Influenza and the flu vaccine (continuing education credit).

PMID- 9004643
TI  - Mental health aspects of publishing: getting yourself psyched.

PMID- 9004642
TI  - Mental health aspects of publishing: Part II.

PMID- 9004645
TI  - Changing childbirth ... changing nothing.

PMID- 9004644
TI  - A different direction.

PMID- 9004646
TI  - Midwive's network.

PMID- 9004647
TI  - Questions & answers in industrial relations.

PMID- 9004648
TI  - Acting as an expert witness. Courtroom skills.

PMID- 9004649
TI  - Remember the managers.

PMID- 9004650
TI  - Midwives and money matters. Why you should consider making a will.

PMID- 9004651
TI  - The role of the midwife in the neonatal unit.

PMID- 9004652
TI  - The use of transcutaneous electrical nerve stimulation on acupuncture points in
      labour.

PMID- 9004653
TI  - Questions & answers in industrial relations.

PMID- 9004654
TI  - Why we should keep an open mind on antenatal visit frequency. A reply to
      Professor Redman.

PMID- 9004655
TI  - Looking through the window ... midwifery in Ontario, Canada.

PMID- 9004657
TI  - Away from home: supporting pregnancy & childbirth in Paris.

PMID- 9004656
TI  - Out in the workplace.

PMID- 9004658
TI  - Risk to profits--risk to babies?

PMID- 9004660
TI  - Mentoring important in skills crosstraining Methodist Richard Young restructures.

PMID- 9004659
TI  - Olympic crowds.

PMID- 9004661
TI  - Applicants show creativity, initiative in acknowledging changes in ESRD
      reimbursement.

PMID- 9004662
TI  - What are the options for nephrologists under capitation?
AB  - Nephrologists will play a pivotal role in changing tomorrow's renal delivery
      system. Nephrologists still control patients and drive the health care delivered
      to patients suffering from ESRD. As a result, practice management companies,
      independent consulting firms, renal societies, hospitals, dialysis providers,
      insurance companies, managed care plans, government agencies, and, yes, even
      independent practice groups are exploring business strategies that will unite
      nephrologists under a common goal--that of an integrated renal delivery network.
      Nephrologists face what is probably their professional career's most important
      business decision: Partner with such organizations as hospitals, dialysis
      providers, or practice management companies, or form an independent nephrologist
      owned IPA and contract with an MSO. As nephrologists evaluate the options, they
      should seek partners that will at a minimum provide the following: a business
      plan that spells out the relationships of all the players; practice evaluations
      that can improved efficiencies; skilled day-to-day practice management; model
      legal documents; human resource management; expert, pro-physician reimbursement
      negotiation, coupled with a system to track contract profitability; case
      management, critical paths, practice guidelines; and renal industry expertise.
      Above all, nephrologists should seek partners in the formation of an integrated
      delivery system that offer an attitude dedicated to physician empowerment in the
      interest of good patient care.

PMID- 9004663
TI  - Options for dialysis providers in a global capitated environment.

PMID- 9004664
TI  - Reorganization of registry aimed at improving response, data collection.

PMID- 9004665
TI  - USRDS. SMRs, crude mortality differ little at most U.S. centers.

PMID- 9004666
TI  - Physician-assisted suicide: a care option for dying patients?

PMID- 9004667
TI  - Issues in ethics.

PMID- 9004669
TI  - ESRD patient support group meets global community online.

PMID- 9004668
TI  - Issues in ethics.

PMID- 9004670
TI  - Cooperative study helps specialists analyze success of PD in children. Data shows
      technique can help reduce peritonitis.

PMID- 9004671
TI  - Dialysis care in Japan: more time doesn't mean better care.

PMID- 9004673
TI  - On choosing a nurse practitioner program--guidelines by which to conduct your
      search.

PMID- 9004672
TI  - Putting prevention into nursing practice.

PMID- 9004674
TI  - Confessions of a nurse practitioner.

PMID- 9004675
TI  - WHO to wipe out smallpox 'by 2000'.

PMID- 9004676
TI  - Reengineering the California raisins.

PMID- 9004677
TI  - Patient restraints.
AB  - This is the first column in a new feature that focuses on the questions health
      care managers ask the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO). Both the JCAHO and Nursing Management's editors urge you,
      the readers, to submit your questions (see address at end of column).

PMID- 9004679
TI  - To your computer, the world really will end soon....
AB  - As the year 2000 approaches, we see it as a time filled with great promise. Our
      computer sees it as the year 1900. Systems will begin to fail as date-sensitive
      materials start to clog the works. Are existing lines of code being rewritten or
      is a new calculator-application being plugged into your computer system to handle
      the situation?

PMID- 9004678
TI  - HEDIS is bigger and better.
AB  - The new Health Plan Employer Data and Information Set (HEDIS) consolidates its
      predecessors for commercial and Medicaid members and includes performance
      measures for Medicare beneficiaries. The new version will arm purchasers and
      consumers with a wealth of information about health maintenance organizations
      (HMOs) and the quality of care provided. The information will help them make
      informed decisions about which health plan to select.

PMID- 9004680
TI  - Labor law update--Part 1.
AB  - To ensure proper actions when making managerial decisions, nurses must be aware
      of labor laws and the policies that apply to them. Part 1 of "Labor Law Update"
      discusses public policy considerations and gender, racial and pregnancy
      discrimination.

PMID- 9004681
TI  - Business ethics: implications for managed care contracts.
AB  - Business ethics is a specialized study that emphasizes how moral standards apply
      to organizations, policies, procedures and behavior. Moral standards must be
      considered to understand the implications of business ethics in subacute care.

PMID- 9004682
TI  - Staff nurse job satisfaction and management style.
AB  - By using appropriate management styles, nurse managers can affect staff nurse job
      satisfaction. A study of 623 staff nurses in three Midwestern hospitals shows
      staff nurse job satisfaction clearly improves as the management style nears the
      participative management style.

PMID- 9004684
TI  - Queen busting. II. Ending the reign.
AB  - Royal behaviours can be found anywhere, even on your unit. A framework is
      provided to "dethrone" hospital royalty. Interpersonal skills are the primary
      weapons in your arsenal.

PMID- 9004683
TI  - Orientation is as simple as 1-2-3.
AB  - How new employees function on the job stems from the orientation. If it is good,
      they will take off and soar. If it is poor, they will have to wade through the
      misinformation and overcome the bad teaching that will ultimately be more costly
      to everyone. Steps for a successful orientation program are given.

PMID- 9004685
TI  - Jurors rate RNs. Counting the costs.
AB  - To gain a perspective on how the public views nurses' legal accountability, a
      group of jurors was surveyed. This study examines the conditions that RNs face,
      as well as their liability under these conditions.

PMID- 9004686
TI  - Supervision. How satisfied are middle nurse managers?
AB  - A study examines the relationship between middle nurse managers' (MNMs) job
      satisfaction and how they perceive their chief nurse executive's (CNE) leadership
      style and adaptability. The CNE's own leadership style and adaptability were
      studied. The study thus examined the interplay between job satisfaction
      (specifically satisfaction with supervision), leadership style and leadership
      adaptability.

PMID- 9004687
TI  - Promoting client satisfaction.
AB  - Traditionally; the client has been seen as a patient with needs rather than a
      consumer with options. Analyzing the perception of the client as well as the
      health care team leads to high standards of cost-effective, quality patient care.
      Client satisfaction is the key to future referrals and hospital revenues.

PMID- 9004688
TI  - A simple guide to nutritional support products.
AB  - In this day of cost-accounting methodologies of care, one must be as objective as
      possible in documenting weight loss as well as caloric need. To address the
      issues of nutritional need, a case study and the patient's assessment are
      presented.

PMID- 9004689
TI  - This I believe ... about the care of human beings.

PMID- 9004690
TI  - Network formation made easier.
AB  - Federal guidelines to determine whether provider networks comply with antitrust
      statutes have been revised. The revisions improve the likelihood that physicians,
      hospitals and other providers will be able to form joint ventures to complete or
      contract with managed health plans. The revisions take on added importance in
      light of managed care's expanding role in Medicare.

PMID- 9004691
TI  - HIV legal update--Part 3.
AB  - The human immunodeficiency virus (HIV) legal update continues to review claims
      involving health care providers. Areas discussed include informed consent
      litigation, confidentiality issues and rights of employees.

PMID- 9004692
TI  - Capitation, point of service and Medicare select: friends or foes.
AB  - Capitation, point of service (POS) and Medicare Select (MedSelect) are
      significantly influencing today's health care system. Providers need to
      understand these key market forces and their implications for subacute care.

PMID- 9004693
TI  - A work site wellness program.
AB  - As a result of a Work Site Wellness Program, 67% of the employees who
      participated improved their health status. The indicators most often met
      included: elimination of back injury, consistent use of seat belts, nonsmoking
      behaviors and reduction in blood pressure, cholesterol and percent body fat.

PMID- 9004694
TI  - Critical pathways and mother-baby coupling.
AB  - Mother-baby couplet care has been utilized for more than 10 years. Both staff and
      patients find use of critical pathways in this managed care system to be very
      effective and efficient.

PMID- 9004695
TI  - Why rural practice?
AB  - In a national study of rural registered nurses, over 3,500 listed family or
      community-related reasons for practicing in rural areas. On the other hand, at
      least half stated that job-related factors would influence them to leave their
      present positions.

PMID- 9004696
TI  - An acute/critical care nurse practitioner program.
AB  - To meet the demands for quality care, nursing education and nursing practice must
      collaborate and integrate services to educate Advanced Practice Nurses (APNs).
      One teaching hospital's successful APN curriculum is described. Topics addressed
      include structural reengineering, continuous quality improvement (CQI) and
      curriculum redesign.

PMID- 9004697
TI  - The operating room of the future.
AB  - As more and more care moves to the home setting, the ability to undergo a
      surgical procedure from the comfort of your own home may not be that far away. As
      for the operating room itself, patient care will be radically different than it
      has been in the past. Radiologists, assisted by computers and robots, may be
      performing procedures on patients "anesthetized" by acupuncture, therapeutic
      touch and aromatherapy in a totally bloodless environment.

PMID- 9004698
TI  - Implementing a patient classification system.
AB  - With the assistance of a consultant, an individualized patient classification
      system (PCS) tool was developed and studies of direct and indirect nursing care
      were conducted, using over 170 patients in a medical/surgical division. Data were
      subjected to linear regression techniques and point values ranges and
      classification categories were established. Also, several significant areas for
      improvement were identified.

PMID- 9004699
TI  - Nurses executive characteristics. Gender differences.
AB  - Do male nurse executives working in a female-dominated profession adopt more of
      the female leadership characteristics? A study investigates gender differences of
      nurse executives on a variety of managerial attributes: sex role, supervision,
      power, career commitment and work/family conflict. Results also were compared to
      executives of other professions.

PMID- 9004700
TI  - Security threats are usually an inside job.
AB  - Although most health care providers fear the unnamed backer, the real risk of
      computer security danger lies in the hands of seemingly innocuous or harmless
      individuals within the institution. Creating information security from the inside
      out is the key to ensuring privacy and confidentiality.

PMID- 9004701
TI  - Infusion pumps.
AB  - Confluence in technologic advances in medical electronics, the availability of
      new intravenous pharmaceuticals, increasing sophistication of home care delivery
      systems and the economic motivations imposed by Diagnosis-Related Groups and
      capitated care payment mechanisms stimulated dramatic developments in intravenous
      delivery technologies, both for the hospital and the outpatient environment.
      Success in the use of these sophisticated drug delivery systems, however, depends
      on appropriate patient selection, optimal selection of a delivery alternative and
      careful patient monitoring for both desired therapeutic response, health delivery
      quality and patient safety.

PMID- 9004703
TI  - We killed the Kardex so the care path could live.

PMID- 9004702
TI  - Unsung heroines. A vision of home care.
AB  - The author provides a poignant narrative reminding nurse managers of their need
      to understand the difficulties and obstacles faced daily by home health aides.
      Sobering accounts describe mistreatment and injustice, often motivated by racial
      and ethnic prejudices. Every nurse manager should ask: "Do I build relationships
      with our aides that shown them they are truly and genuinely valued?"

PMID- 9004705
TI  - Reforms round-up. Welcoming a new era.

PMID- 9004704
TI  - Seeing the disabled as people first.

PMID- 9004707
TI  - 'Drying out' at home.

PMID- 9004706
TI  - Pay rates differ significantly.
AB  - An NZNO survey reveals large differences in pay rates for nurses with the same
      level of experience and expertise working in the public health sector. The cause-
      the Employment Contracts Act.

PMID- 9004708
TI  - Learning from midwives.

PMID- 9004709
TI  - Keeping people in the community. Interview by Anne Manchester.

PMID- 9004710
TI  - Depression guidelines published.

PMID- 9004711
TI  - Dealing with depression.

PMID- 9004712
TI  - Lobbying is the way of the future.

PMID- 9004713
TI  - Revisiting the health reforms.

PMID- 9004714
TI  - Creating a safe cultural space.

PMID- 9004715
TI  - Understanding managed care.

PMID- 9004716
TI  - Raising the profile of nurses.

PMID- 9004718
TI  - [Special issue on gynecologic pathology].

PMID- 9004717
TI  - Handling sharps with care.

PMID- 9004719
TI  - [European recommendations for quality assurance in the setting of mammographic
      screening for breast cancer. Report of pathologists of the working group "Breast
      Cancer Screening" of the European Union].

PMID- 9004720
TI  - [Vulvar dermatoses and intra-epithelial neoplasia. Classification, criticism and
      suggestions].

PMID- 9004721
TI  - [Cervical smears and evaluation of quality].

PMID- 9004722
TI  - [Cervical smears. Contribution of automated screening].

PMID- 9004723
TI  - [Follow-up and treatment of cervical intraepithelial neoplasia (current trends)].

PMID- 9004724
TI  - [Genital infection with human papillomavirus (HPV): viral screening and typing,
      importance of in situ hybridization].

PMID- 9004725
TI  - [Adenocarcinoma in situ of the cervix uteri. Cytologic and histologic aspects].

PMID- 9004726
TI  - [Dysfunctional endometrial hemorrhage. Contribution of biopsy and curettage].

PMID- 9004727
TI  - [Contribution of pathology in procedures for medically assisted reproduction].

PMID- 9004728
TI  - [Borderline ovarian tumors. Current data].

PMID- 9004730
TI  - [Marfan's syndrome].
AB  - We report our experience in the diagnosis, evaluation and counseling for the
      Marfan Syndrome in 35 individuals of 23 families. Utilizing the new clinical and
      diagnostic criteria, we observed that the frequency of the systems affected
      corresponds to those found in the literature. Presymptomatic treatment is
      possible, and considering the family history in the diagnosis is needed for
      adequate genetic counseling and the well-being of the affected patient.

PMID- 9004729
TI  - [To be physician].

PMID- 9004731
TI  - [Ebola: "a fatal syndrome"].
AB  - No other clinical entity has attached more attention now-a-day than those
      precipitated by the infection with a Hemorrhagic Fever Virus. Potentially caused
      by Arena, Bunya, Flavi, and Filoviradae, only the latter has had such a major
      impact throughout the world. Two major genuses have been recognized since they
      become evident for the first time in 1967, the single-species Marburg, and the 3
      species-Ebola (E. zaire, sudan and reston). With the exception of the 2 outbreaks
      of E. reston (Washington, USA 1989-1993), all of them have taken place in Africa,
      where the virus is still hiding among the wild-life of the Tropical Rain Forest.
      Currently (in April 1995) the reemergence of Ebola virus has once more proven its
      fatality, leaving around 170 deaths in Zaire, 250 miles from its capital,
      Kinshasa. There is worldwide alert, sponsored by the CDC in Atlanta, the World
      Health Organization and the authorities in Zaire regarding its potential
      spreading to naive regions, in and out of Africa. The characteristic clinical
      picture of a viral hemorrhagic fever has no match. After a 2-21 days incubation
      period a viral-like illness develops. As days go by, symptoms worsen, and by the
      7th day, a severe and diffuse bleeding tendency ensues. The individual's death is
      the most likely outcome in the great majority of cases. As a lethal virus,
      without an available treatment and a possible airborne-route of transmission,
      Ebola virus will always be considered a persistent threat to the global health.

PMID- 9004732
TI  - (Ethanol)(2,3,7,8,12,13,17,18-octaethylporphinato)manganese(III) perchlorate.
AB  - The crystal structure of [Mn(C36H44N4)(C2H6O)]ClO4 has been determined. The
      average Mn-Np bond distance is 1.997 (5) A and the axial Mn-O bond length is
      2.145 (2) A. The manganese(III) ion has a displacement of 0.17 A from the mean
      plane of the 24-atom porphinato core.

PMID- 9004733
TI  - L-histidine methyl ester dihydrochloride.
AB  - The title compound, C7H13N3O2(2+).2Cl-, has distances and angles quite similar to
      those of histidine hydrochloride monohydrate [Donohue & Caron (1964). Acta Cryst.
      17, 1178-1180], except for the distances within the ester functionality.

PMID- 9004735
TI  - [Characteristics of a new controlled release formulation of ursodesoxycholic
      acid].
AB  - Ursodeoxycholic acid, like all weak acids, has to be formulated so as his release
      and absorption depend as little as possible by the pH of gastrointestinal tract.
      To obtain this result a controlled release formulation of UDCA was developed,
      based on bioadhesive technique. This allowed a longer residence and absorption
      time of the active ingredient both at gastric (due to gastrosoluble rate) and
      duodenal-jejunum level (gastroresistant rate). Thus, all the absorption windows
      for bile acids are utilized, to ameliorate the total bioavailability of the drug.

PMID- 9004734
TI  - A diacetylmorphine polymorph.
AB  - The title compound, 7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diyl
      diacetate, C21H23NO5, was crystallized from a solution of its hydrochloride and
      sodium acetate. Unlike prior reports in which crystals were hexagonal shaped
      (orthorhombic) and in space group P2(1)2(1)2(1), the crystals in the present
      determination grew as large prisms (monoclinic) and were in space group P2(1).

PMID- 9004736
TI  - Syntheses and pharmacological properties of new 2-aminobenzimidazole derivatives.
AB  - The paper reports the structures, syntheses and pharmacological properties of new
      compounds having a 2-aminobenzimidazole group. They exhibit various activities:
      histamine H1- and H2-receptors blocking activities, antilipidemic and platelet
      antiaggregatory, anti-inflammatory and analgesic properties, antimicrobial,
      fungicidal, parasiticide, antiarrythmic activity and muscle relaxant, comparable
      to those of drugs used in therapy.

PMID- 9004737
TI  - Synthesis of indole-N-propionitrile, N-propionic acid and N-propionamide
      derivatives of potential biological activity.
AB  - Cyanoethylation of a selected group from indole derivatives 1a-i using
      acrylonitrile in pyridine and potassium hydroxide afforded the corresponding
      indole-1-propionitrile 2a-h derivatives which readily hydrolysed in basic medium
      to the corresponding indole-1-propionic acid derivatives 4a-c. A several attempts
      to cyclize the above products-to the corresponding dihydropyrroloquinolin-4-one
      derivatives. The indole-1-propionamide derivatives reacted with diethyl carbonate
      and ethyl acetate under Claisen condensation also, with diazonium salts and
      nitric acid.

PMID- 9004738
TI  - Metabolism of goniothalamin in animal and microbial system.
AB  - Of the twenty microorganisms screened for metabolism of goniothalamin only
      Streptomyces aurofaciens ATCC 10762 and Nocardia species NRRL 5646 produced two
      metabolites, 3,4-dihydrogoniothalamin and 3,4,7,8 tetrahydrogoniothalamin. The
      identity of the isolated metabolites were established using TLC, HPLC, MS, IR,
      and 1H- and 13C-NMR spectroscopy. In addition, the substrate had been transformed
      into two unknown metabolites by Aspergillus niger ATCC 11394 and Septomyxa
      affinis ATCC 6737 in low yield. Three of the metabolites were also detected and
      identified in the urine and blood samples of the goniothalamin-treated Sprague
      Dawley rats. The obtained results are in agreement with and support the principle
      of microbial models of mammalian metabolism.

PMID- 9004739
TI  - [Biological activity of a carrier molecule-iron complex: probable mechanisms of
      intestinal absorption].
AB  - The physical-chemical properties of a new Iron-Protein complex, the so called
      "Iron Yeast" biotecnologically produced by Saccharomyces cerevisiae cell
      cultures, are reported. Using atomic absorption methods the amount of free iron
      in the complex has been evaluated, ascertaining that 99% of Iron is structurally
      bound to the protein matrix. Iron Yeast is a further, original contribution to
      the treatment of iron-deficiency anemias, showing a satisfactory clinical
      activity and a lower amount of undesired side effects in comparison with other
      Iron-Protein complexes.

PMID- 9004741
TI  - [Gait disorders in the elderly].

PMID- 9004740
TI  - Interactions between gramicidin S and its producer, Bacillus brevis.
AB  - Gramicidin S (GS) inhibition of germination outgrowth of Bacillus brevis spores
      was reversed completely by a short pretreatment with sodium dodecyl sulfate,
      moderately by ethanol or by incubation at pH 10 but not by incubation at pH 4. Of
      five metal ions tested (Na+, Mg2+, Fe2+, Cu2+, Ca2+), only Ca2+ reversed GS
      inhibition. When Ca2+ (but not the other four metal ions) was added to the growth
      medium, there was a considerable portion of the biosynthesized GS found in the
      extracellular fluid. These findings are interpreted in terms of the binding of GS
      to the external layers of the B. brevis spore.

PMID- 9004742
TI  - [Chronic disequilibrium in the older patient: investigation of reversible cases
      in a 22-patient series].
AB  - Chronic instability is a frequent complaint in elderly patients. As literature on
      the subject is scarce, we investigated reversible causes, evaluating patients
      over 65 years of age referred to a regional neurological practice for
      disequilibrium lasting longer than three months. Clinical features were analyzed.
      Computerized tomography (CT) of the brain, and thyroid hormone and cyanocobalamin
      (Cc) serum levels were studied for all patients, as was clinical course. No CT
      abnormalities were found. Low Cc levels were observed in 6 patients, and 2 were
      diagnosed of previously undetected hypothyroidism. During the mean follow-up
      period of 12 months, improvement was seen in 3 specifically-treated patients, one
      with hypothyroidism and two with Cc deficit. We conclude that chronic instability
      in the older patient cannot usually be traced to a specific cause, but that it is
      important to protocolize the assessment of such patients, including routine tests
      for thyroid hormone and Cc levels, in order to rule out treatable causes.

PMID- 9004744
TI  - [Depression and Parkinson's disease: neurobiologic foundations and therapeutic
      management].
AB  - The prevalence of depression in Parkinson's disease (PD) is estimated to be
      around 40% and generally takes the form of dysthymia. Although psychological
      factors probably contribute to depression, data point to a relation to structural
      and biochemical changes linked to PD. Thus, the onset of motor impairment is
      often preceded by a depressive episode, although there is no consistency between
      the seriousness of motor disability and depression. Furthermore, depression
      aggravates the memory and language impairments of PD and is thought to be a risk
      factor for developing dementia. Regional cerebral blood flow abnormalities in the
      medial frontal and cingulate cortices and low 5-HIIA concentrations in cerebro
      spinal fluid suggest that degeneration of the mesocorticolimbic dopaminergic
      system as well as dorsal raphe changes may be implicated. Assessment of
      depression in PD is difficult, as none of the currently available scales were
      specifically designed for patients with this disease Furthermore, there is a lack
      of well-controlled studies showing that current antidepressants are effective in
      PD patients or are safe for use when the motor, cognitive and autonomic
      impairments of PD are present.

PMID- 9004743
TI  - [Automatic anatomic-physiologic correspondence of deep structures of the central
      nervous system in stereotaxic functional neurosurgery].
AB  - This work describes in detail the graphic facilities of a neurosurgical deep
      recording system for the anatomic-physiologic analysis of central nervous system
      deep structures in stereotaxic function neurosurgery guided by deep semi
      microrecordings of the brain, as developed by the International Center of
      Neurologic Restoration in Cuba. This system for digitization of electrical
      activity in the brain uses an IBM-compatible 80386/80486 microprocessor in place
      of analog equipment for the visualization and recording of signals, thereby
      providing easier manipulation of recorded data and greater flexibility of
      analysis. The system automatically integrates each pulse recorded and quantifies
      its average amplitude. For each brain region explored, the behavior of the
      integrated activity recorded can be displayed on the corresponding sagittal view
      from the cerebral atlas of Schaltenbrand-Wahren, and then automatically scaled to
      the anatomic dimensions of each patient. The picture, with its different options,
      Facilitates analysis of anatomic correspondence of deep electrophysiologic
      signals so the various structures, nuclei and specific neuronal groups can be
      precisely located in the patient's brain. To date the system has been used
      successfully in over 110 neurosurgical procedures ventral intermedios (vim)
      thalamotomy, pallidotomy, subthalotomy and neurotransplantation, providing more
      certain location of lesions or grafting sites for managing symptoms in
      Parkinson's disease and other movement disorders.

PMID- 9004745
TI  - [Implicit memory in Alzheimer's disease].

PMID- 9004746
TI  - [Deafness from leptomeningeal metastasis].

PMID- 9004747
TI  - [Paradoxical embolism: diagnosis by transcranial Doppler ultrasonogram with
      contrast].

PMID- 9004748
TI  - [Cerebrovascular disease as a form of presentation of HIV infection].
AB  - Several necropsy reports have suggested that cerebral vascular disease (CVD) is
      more frequent in HIV positive patients than in HIV negative individuals of the
      same age, although clinical signs are rare. We describe three patients for whom
      CVD was the clinical manifestation that led to diagnoses of HIV infection. The
      patients were two men and a woman aged 29, 52 and 66, respectively, with
      differing risk factors for CVD: smoking (3), blood hypertension (2), endocarditis
      (1) and free protein S deficiency (1). The risk factors for HIV infection were
      also different. The CVD diagnoses were confirmed by computed tomography, which
      revealed lacunar infarction in two cases with favorable outcomes and embolia-like
      infarction with subarachnoid hemorrhage in the third patient, who died a few days
      later. CD4 levels varied (50, 130 and 689/mm3). Our observations lead us to the
      following conclusions: 1) CVD can be a first clinical manifestation of HIV
      infection and the disease that allows seropositivity to be diagnosed. Although
      CVD usually presents in advanced stages of HIV infection, it can also occur in
      seropositive patients who do not meet the criteria for AIDS. 2) The classical
      risk factors for vascular disease probably play a dominant role in the etiology
      of CVD in such patients, alongside systemic complications related to the virus;
      the direct role of HIV remains to be determined. 3) AIDS should be considered and
      ruled out in patients with CVD who are at risk for HIV infection, even in older
      patients with vascular risk factors.

PMID- 9004749
TI  - [Intracranial pressure monitoring and eclampsia].
AB  - Intracranial pressure (ICP) monitoring has been shown to improve clinical
      pharmacological treatment of intracranial hypertension (ICH) in a rising number
      of situations, assuring effective cerebral perfusion pressure (CPP) and,
      concomitantly, reducing the risk of brain ischemia. Although its use in entities
      such as eclampsia have been reported, the continuous use of ICP monitoring is
      restricted. We report the case of an eclampsic woman in whom ICP was monitored.
      Recordings allowed CPP to be correctly stabilized, with strict correlation
      between ICP and tomographic measurements of density. We also review the
      pathophysiologic mechanisms that have been proposed to cause ICH in eclampsia and
      emphasize the usefulness of ICP monitoring to manage this complication.

PMID- 9004751
TI  - [Palinopsia: first manifestation of a brain metastasis].

PMID- 9004750
TI  - [Subclinical hypothyroidism as a cause of reversible cognitive deterioration].
AB  - Hypothyroidism, which is treatable by hormone substitution, is one of the most
      frequent causes of symptomatic dementia. The effectiveness of hormone therapy for
      improving mental status is well established, but full reversibility of symptoms
      is unusual. We report the case of a woman whose disease began with progressive
      cognitive deterioration and tremor; laboratory tests revealed subclinical
      hypothyroidism, which was watched carefully over the next three years. When
      thyroid hormone therapy was begun, there was marked clinical improvement, which
      reversed only when the patient voluntarily withdrew treatment for a few weeks.

PMID- 9004752
TI  - [Spontaneous intracranial hypotension and sixth cranial nerve paralysis].

PMID- 9004753
TI  - Pierre Auger--a life in the service of science.
AB  - A short biography of Pierre Auger, the discoverer of the atomic auger electron
      effect, is given. Professor Auger's outstanding professional career covered
      physics, nuclear power and space research, organization and administration of
      research, diplomatic services and pedagogics but also extended into modern
      biology, humanistic sciences, poetry and arts. Part of a speech in Paris of
      professor Auger held in 1989 on the theme 'Research and Creativity' at an
      international symposium on the auger effect is included in this biography as well
      as one of his poems.

PMID- 9004754
TI  - Biophysical aspects of Auger processes--A review.
AB  - Radionuclide decay by electron capture and/or internal conversion is accompanied
      by complex atomic vacancy cascades and emission of low-energy electrons,
      resulting in a highly charged daughter atom and a high density of electron
      irradiation in the immediate vicinity of the decay site. The molecular and
      cellular consequences of such decay events include DNA strand breaks, mutations,
      chromosome aberrations, malignant transformation, division delay, and cell death.
      Damage to cells depends largely on the intracellular location of the
      radionuclide. Decays outside the cell nucleus produce low-LET-type radiation
      effects (RBE approximately 1). In contrast, decays in DNA cause pronounced high
      LET-type effects (RBE approximately 7-9). However, recent studies suggest that
      even for DNA-associated Auger emitters cell damage can be modified to resemble
      the pattern observed with low-LET radiations. These findings indicate that the
      molecular and cellular mechanism(s) responsible for the cytotoxic effects of
      Auger emitters remain obscure.

PMID- 9004755
TI  - Strand breaks in plasmid DNA following positional changes of Auger-electron
      emitting radionuclides.
AB  - The purpose of our studies is to elucidate the kinetics of DNA strand breaks
      caused by low-energy Auger electron emitters in close proximity to DNA.
      Previously we have studied the DNA break yields in plasmids after the decay of
      indium-111 bound to DNA or free in solution. In this work, we compare the DNA
      break yields in supercoiled DNA of iodine-125 decaying close to DNA following DNA
      intercalation, minor-groove binding, or surface binding, and at a distance from
      DNA. Supercoiled DNA, stored at 4 degrees C to accumulate radiation dose from the
      decay of 125I, was then resolved by gel electrophoresis into supercoiled, nicked
      circular, and linear forms, representing undamaged DNA, single-strand breaks, and
      double-strand breaks respectively. DNA-intercalated or groove-bound 125I is more
      effective than surface-bound radionuclide or 125I free in solution. The hydroxyl
      radical scavenger DMSO protects against damage by 125I free in solution but has
      minimal effect on damage by groove-bound 125I.

PMID- 9004757
TI  - DNA strand breakage by 125I-decay in a synthetic oligodeoxynucleotide--2.
      Quantitative analysis of fragment distribution.
AB  - The DNA breakage produced by decay of 125I in a double-stranded 41 bp
      oligodeoxynucleotide was investigated by DNA sequencing gel analysis. Use of both
      5'- and 3'-end 32P labelling of the 125I containing strand provided the single
      stranded breakage pattern at either side of the 125I-dC. The asymmetric pattern
      of breakage relative to the 125I-labelled nucleotide enabled deconvolution of two
      components of breakage. One of them declines very quickly with nucleotide number
      from 125I-dC and dominates within 4-5 nucleotides. We assume this component to be
      associated with neutralisation of charged Te atom resulted from decay, or/and
      with radiation damage to an initial target other than the deoxyribosyl moiety-
      probably the bases. The second component depends on the geometrical distance
      between the 125I atom and deoxyribosyl atoms. These two components are
      responsible for breakage under conditions limiting radical mediated damage,
      namely in the presence of 2M dimethylsulphoxide. The third component, associated
      with radical-mediated damage, contributes to the total breakage during incubation
      in 20 mM phosphate buffer alone, and under these incubation conditions dominates
      the breakage beyond 8-9 nucleotides from 125I-dC. The estimated average numbers
      of single-stranded breaks produced in the 125I-containing strand by each
      mechanism in 41-mer oligodeoxynucleotide with 125I-dC at 21st position are
      respectively 2.33, 0.98 and 0.63.

PMID- 9004756
TI  - DNA strand breakage by 125I-decay in a synthetic oligodeoxynucleotide--1.
      Fragment distribution and evaluation of DMSO protection effect.
AB  - A double stranded oligodeoxynucleotide containing a single 125I-dC in a defined
      location was used to investigate DNA strand breakage resulting from 125I decay.
      Samples of a 41 bp oligodeoxynucleotide were incubated in 20 mM phosphate buffer
      (PB), or PB plus 2 M dimethylsulphoxide (DMSO), at 4 degrees C during 18-20 days.
      The 32P-5'-end labelled DNA fragments produced by 125I decays were separated on
      denaturing polyacrylamide gels, and the 32P activity in each fragment was
      determined by scintillation counting after elution of fragments from gel. Most of
      the breaks, around 90%, occurred within 4-5 nucleotides of the 125I-dC, but DNA
      breaks were detected up to 16 nucleotides from the decay site. The 125I-dC was
      located at the 21st nucleotide from the 32P-5'-end label, and since 32P was not
      detected in fragments longer than 20 nucleotides, it was assumed that all 125I
      decay events produce at least one break in the 125I-labelled DNA strand. The
      results show a considerable protection effect of DMSO on DNA breaks at sites >5-6
      nucleotides from the 125I location. The probability of breaks in this region was
      decreased with DMSO by a factor of 2 to 8-fold, suggesting significant role for
      radical-mediated DNA breaks at the more distant sites. However, the total
      protection effect of DMSO is rather small: 1.1, because of the small contribution
      of breakage at distant sites to the total yield.

PMID- 9004758
TI  - Sequence-specific DNA breaks produced by triplex-directed decay of iodine-125.
AB  - Triplex forming oligonucleotides (TFO) labeled with Auger emitters could be ideal
      vehicles to deliver radioactive-decay energy to specific DNA sequences, causing
      DNA breaks and, subsequently, inactivation of these sequences. To demonstrate
      this approach we labeled with 125I (two 125I per molecule on average) a purine
      rich 38-mer which forms a stable triplex with a polypurine x polypyrimidine
      stretch in the human HPRT gene. Decay of 125I in the bound TFO was shown to cause
      sequence-specific double strand breaks (DSB) in the target HPRT sequence cloned
      into plasmid DNA. No sequence-specific breaks were observed if 125I-labeled TFO
      were not bound to the plasmid DNA. After 60 days of decay accumulation (one 125I
      half-life) approximately a quarter of all plasmid molecules contained sequence
      specific DSB, corresponding to 0.3 site-specific DSB per decay. Sequencing gel
      analysis shows that the DNA breaks are distributed within a few bases of the
      maxima at those bases opposite to the positions of 125I in the TFO.

PMID- 9004759
TI  - DNA damage, micronucleus formation, and cell death from 125I decays in DNA.
AB  - CHO cells were pulse-labeled with 125I-iododeoxyuridine, harvested 30 min or 5 h
      after labeling, and stored at -196 degrees C for accumulation of 125I decays. The
      30- min groups yielded low-LET survival curves (large shoulder, D0 136
      decays/cell); 5-h groups showed a high-LET pattern of cell killing (no shoulder,
      D0 45 decay/cell). Surprisingly, the shift in 125I action was abolished in cells
      exposed to HAT medium; both 30-min and 5-h cell groups exhibited high-LET-type
      killing (no shoulder, D0 52 decays/cell). The striking difference in cell death
      was not accompanied by any change in induction or repair of DNA DSBs, but the
      pattern of micronucleus formation (and by implication chromosome damage) did
      parallel 125I-induced cell death. These findings suggest that cell killing may
      not be directly linked to the absolute number of DNA DSBs and that damage to
      higher-order genome structures may be an important factor in radiation-induced
      cell death.

PMID- 9004760
TI  - Cellular and subcellular studies of the radiation effects of Auger electron
      emitting estrogens.
AB  - We studied the effect of 123I-labeled estrogen (123I-E) in estrogen receptor (ER)
      rich cells in culture and in cell free model systems in vitro to elucidate the
      nature of the radiotoxicity for ER + cells of estrogens containing nuclides which
      emit Auger electrons. In cells the 123I-E caused a dose-dependent, unlabeled
      estrogen-inhibitable induction of chromosome aberrations. A dose of about 1000
      decays per cell, which is approximately the mean lethal dose for these cells,
      resulted in an average of 1 chromosome break per cell. This supports the
      hypothesis that the lethal lesion induced by 123I-E is a chromosome break.
      Incubation of 123I-E/ER complex, but not 123I-E alone, with 27-mer duplex
      estrogen response element (ERE) DNA produced a dose-dependent cleavage of the
      ERE. However, we were unable to detect any fragmentation of either the 66 kDa
      full length ER in cell extracts or a purified 31 kDa hormone binding domain when
      incubated with excess 123I-E. Thus it appears that 123I-E effects its
      radiotoxicity by binding to ER, associating with ERE DNA and, by directing high
      LET radiation to DNA, inducing lethal chromosome breaks.

PMID- 9004762
TI  - Modelling of Auger-induced DNA damage by incorporated 125I.
AB  - We have analyzed a newly available high resolution and precision repeat of the
      original Martin and Haseltine experiment which includes the influence of DMSO on
      the results. The new model includes the production and diffusion of radical
      species and .OH radical attack on DNA as well as the direct hits. Calculations of
      single-strand breaks use individual Auger electron along with the tracks of
      electrons and radical species superimposed on an atomistic model of B-DNA.
      Comparison of the preliminary calculations with the experiment supports the
      earlier choice of data for the amount of energy required to produce a single
      strand break, i.e. 17.5 eV. In a separate simulation we found that an average of
      less than two ionizations inducing a single-strand break gave the best fit to
      experimental data. Direct hits were found to be predominantly occurring at short
      range while the damage by .OH radicals was mainly of the long-range type.

PMID- 9004761
TI  - DNA damage induction by 125I-estrogen.
AB  - DNA damage induced by the radioactive decay of 125I-estrogen (125I-VME2) in an
      estrogen receptor expressing CHO cell line, CHO-ER, was measured. 125I-VME2
      targeted 125I atoms proximal to DNA estrogen response elements (EREs). 125I
      decays were accumulated at -135 degrees C, and thereafter assayed by alkaline and
      neutral filter elution techniques to measure DNA single strand break (ssb) and
      double strand break (dsb) induction respectively. Increasing DNA damage (both
      ssbs and dsbs) was detected after exposure of cells to increasing concentrations
      of 125I-VME2. DNA ssb and dsb dose-response curves for 125I-VME2 were
      multiphasic. The rates of DNA damage induction by the decay of 125I-VME2 was
      determined by comparing slopes of all data or by comparing initial slopes. DNA
      ssb induction per 125I-VME2 decay was approximately 2 times greater compared with
      DNA dsb induction. 125I-VME2 decay induced approximately 4-8 times more DNA dsbs
      than 125IUdR decay.

PMID- 9004763
TI  - Modelling of initial events and chemical behaviour of species induced in DNA
      units by Auger electrons from 125I, 123I and carbon.
AB  - Auger electron spectra for 123I and 125I generated by Monte Carlo calculation and
      Auger electrons emitted from carbon after photoelectric effect on its K-shell as
      well as two DNA models (linear plasmid and nucleosome model) based on x-ray
      diffraction experiments have been used to simulate the behaviour of all species
      and radicals created during the physical and the chemical phase of the Auger's
      transport. By introducing appropriate assumptions for the induction of strand
      breaks the number of these breaks can also be determined and correlated to
      experimentally found numbers of lethal events. Efficiency differences between the
      iodine nuclides themselves and in comparison with the rather monoenergetic Auger
      electrons from carbon are shown with regard to the direct and indirect effects on
      the two DNA models. The characteristic products in the physical, chemical and
      biochemical phase are compared with corresponding results from the literature for
      low-LET radiation.

PMID- 9004764
TI  - Auger-electron spectra of radionuclides for therapy and diagnostics.
AB  - The present paper documents the calculation of radiation spectra and of radial
      dose distribution around a point source for 24 selected radionuclides. The
      radionuclides were ordered into three groups: Nuclides potentially useful for
      therapy by emission of Auger electrons: 51Cr, 64Cu, 67Ga, 73Se, 75Se, 77Br,
      80mBr, 94Tc, 99mTc, 114mIn, 115mIn, 123I, 124I, 125I, 167Tm, 193mPt, and 195mPt,
      nuclides potentially useful for therapy by alpha-particles with additional
      emission of Auger electrons: 212Bi, 211At and 255Fm, and nuclides potentially
      useful for electron Auger-therapy with simultaneous PET diagnosis: 73Se, 94Tc and
      124I. The calculations imply strongly the development of labelled DNA-seeking
      compounds useful as carrier for the Auger- and Coster-Kronig electron-emitting
      radionuclides.

PMID- 9004765
TI  - Detection of Auger enhancement induced in HeLa cells labeled with
      iododeoxyuridine and irradiated with 150 kV x-rays--Effects of cysteamine and
      dimethylsulfoxide.
AB  - We examined the effects of cysteamine and dimethylsulfoxide on the lethality of
      iododeoxyuridine-labeled HeLa cells irradiated with 150 kV x-rays (effective
      energy was 48 keV) and compared with those irradiated with 60Co gamma-rays. The
      protectable fraction was estimated from the regression lines for the reciprocal
      plots of the concentration of protectors, versus the degree of protection. The
      protectable fraction by cysteamine was 9.4% lower in iododeoxyuridine-labeled
      cells than in control cells when they were irradiated with x-rays, whereas no
      such difference was observed with dimethylsulfoxide. The slopes of the regression
      lines were steeper (i.e., more difficult to protect) for both protectors in
      iododeoxyuridine-labeled cells irradiated with x-rays. No such differences were
      observed in gamma-irradiated cells. The cause for these differences are
      attributable to Auger enhancement. The results suggest that at least a portion of
      Auger enhancement is not protectable by cysteamine and is hard to be protected by
      both protectors cysteamine and dimethylsulfoxide.

PMID- 9004766
TI  - Radiolytic products of bromodeoxyuridine in solids by 60Co gamma-rays and
      monoenergetic soft x-rays at the K-absorption edge of bromine.
AB  - In order to investigate DNA damage due to Auger cascades in bromodeoxyuridine
      (BrdU), BrdU mixed with other nucleosides, as a model of DNA, was irradiated in
      solids by gamma-rays and monoenergetic x-rays at around the K-absorption edge of
      bromine (13.47 keV). The main products of BrdU were deoxyuridine produced through
      debromination, and bromouracil produced through the decomposition of a sugar
      group. The rates of the debromination and the nucleobases release of additives
      were markedly increased in the mixed sample. This observation indicated that the
      additives surrounding BrdU efficiently supplied protons and then decomposed. The
      major products by x-rays were the same as those by gamma-rays, indicating that
      Auger cascades in bromine atoms did not produce specific products. The production
      rates for all products from the mixed sample were about 2.5 times higher at 13.51
      (above the K-absorption edge) keV than at 13.43-keV x-rays.

PMID- 9004767
TI  - Double-strand breaks in DNA induced by the K-shell ionization of calcium atoms.
AB  - A calcium (Ca)-DNA complex in a buffered aqueous solution was irradiated with
      monochromatic x-rays at around the K-shell absorption edge of the Ca atom. The
      energies were 4.030 and 4.071 keV, which correspond to slightly below and above
      the K-shell absorption edge of Ca (4.047 keV). The number of double-strand breaks
      (DSB) and single-strand breaks (SSB) per one molecule of Col E1 DNA was
      calculated using Povirk's equation after the electrophoretic separation of three
      forms of plasmid DNA (forms I, II and III, which are supercoiled closed circular,
      open circular and linear, respectively). In a solution with Ca ions, the DSB
      yield in DNA irradiated with 4.071 keV x-rays is 1.27 times higher than that with
      4.030 keV x-rays. In contrast, in the absence of Ca ions, the DSB yield is the
      same at both the x-ray energies. The SSB yields are also independent of the x-ray
      energy in the presence and absence of Ca ions. A reference experiment regarding
      irradiation with 60Co gamma-rays shows that the ratio of the DSB yield to the SSB
      yield upon irradiation with 4.071 keV x-rays is higher (factor of 3.2) than that
      with 60Co gamma-rays.

PMID- 9004769
TI  - Determination of atomic local order in thyroid hormones by extended x-ray
      absorption fine structure [EXAFS] for radiation dose estimates.
AB  - Dosimetry from 125I emitting Auger electrons in the follicles of the thyroid will
      improve when their complete interaction with the molecular structure about the
      Auger emitting atoms is known to Angstrom distances. Extended x-ray absorption
      fine structure (EXAFS) can provide this information. EXAFS experiments gave
      intermolecular and intramolecular distance for pure solid L-thyroxine (T4)
      (C15H11I4NO4) using a model based on crystalline T4 hydrochloride monohydrate
      (C15H11I4NO4HCl.H2O). For a solution of L-thyroxine the structure consists of the
      intramolecular distances found for T4 and an additional shell of four carbon
      atoms distances of 2.01 A. Atomic density functions from Fourier transformed
      EXAFS measurements are suitable for estimating very short range interactions of
      Auger electrons in thyroid thyroglobulin over a radial distance of 7.71 A.
      Examination of density functions provided a plausible argument for the difference
      in biological effect between 131I and 125I in the thyroid.

PMID- 9004768
TI  - Lethal effect of K-shell absorption of intracellular phosphorus on wild-type and
      radiation sensitive mutants of Escherichia coli.
AB  - The present study was conducted to clarify the lethality of Auger cascades
      induced by the K-shell photoabsorption of phosphorus in Escherichia coli. Killing
      of wild-type and radiation-sensitive mutants of E. coli was examined. Three x-ray
      energies were chosen for irradiation; at 2.153 keV: the resonance peak of K-shell
      photoabsorption of phosphorus; at 2.146 and 2.160 keV: off-peak. Enhancement
      ratio, which was defined as the ratio of the killing sensitivity of 2.153 keV to
      that at 2.146 keV, were 1.32 to 1.54 for examined strains. Increment of absorbed
      energy calculated in entire cells for 2.153 keV radiation could not explain the
      degree of observed enhancement of killing. Lethality of Auger cascades depended
      on the killing sensitivity with x-rays which did not induce Auger cascades. The
      lethality for wild-type was lower than that for recombination repair-deficient
      mutants. It was concluded that one part of damages produced by Auger cascades was
      repaired in wild-type strains.

PMID- 9004771
TI  - Calculation of equivalent dose for Auger electron emitting radionuclides
      distributed in human organs.
AB  - Radionuclides that emit Auger electrons can be extremely radiotoxic depending on
      the subcellular distribution of the radiochemical. Despite this, ICRP 60 provides
      no guidance in the calculation of equivalent dose H(T) for Auger electrons. The
      recent report by the American Association of Physicists in Medicine recommends a
      radiation weighting factor wR of 20 for stochastic effects caused by Auger
      electrons, along with a method of calculating the equivalent dose that takes into
      account the subcellular distribution of the radionuclide. In view of these
      recommendations, it is important to reevaluate equivalent doses from Auger
      electron emitters. The mean absorbed dose per unit cumulated activity (S-value)
      from Auger electrons and other radiations is calculated for ninety Auger-electron
      emitting radionuclides distributed in human ovaries, testes and liver. Using
      these S-values, and the formalism given in the recent AAPM report, the dependence
      of the organ equivalent doses on subcellular distribution of the Auger electron
      emitters is examined. The results show an increase in the mean equivalent dose
      for Auger electron emitters when a significant fraction of the organ activity
      localizes in the DNA.

PMID- 9004770
TI  - Radioprotection by DMSO against the biological effects of incorporated
      radionuclides in vivo--Comparison with other radioprotectors and evidence for
      indirect action of Auger electrons.
AB  - Dimethyl sulfoxide (DMSO) was studied for its capacity to protect against the
      biological effects of chronic irradiation by incorporated radionuclides.
      Spermatogenesis in mice was used as experimental model and spermatogonial cell
      survival was the biological endpoint. DMSO was injected intratesticularly 4 h
      prior to a similar injection of the radiochemical and the spermhead survival
      determined. Iodine-125 was localized in either the cytoplasm (H125IPDM) or in the
      DNA (125IUdR) of the testicular cells. Protection was observed against the high
      LET type effects of DNA-bound 125I as well as the low-LET effects of
      cytoplasmically localized 125I with dose modification factors (DMF) of 3.1+/-1.0
      and 4.4+/-1.0 respectively. No protection (DMF = 1.1+/-0.1) was observed against
      the effects of high-LET 5.3 MeV alpha particles of 210Po. The present findings
      provide supporting evidence that the mechanism responsible for the extreme
      biological damage caused by DNA-bound Auger emitters is largely radical mediated
      and therefore indirect in nature.

PMID- 9004772
TI  - The biological effects of Auger electrons compared to alpha-particles and Li
      ions.
AB  - The present study reports the results of V-79 Chinese hamster cell survival
      studies in which Auger electron emission was stimulated in gadolinium (Gd) after
      thermal neutron capture. When a porphyrin that had previously been labeled with
      boron (10BOPP) was also labeled with Gd (Gd-10BOPP), the cells were incubated
      with Gd-10BOPP to assess the compound's ability to physiologically transport the
      Gd into the cell, and localize the Gd atoms in or near the cell's critical
      target, presumably the DNA. It was anticipated that Auger electron emission,
      stimulated during the 157Gd (n, gamma)158Gd interaction, would impart additional
      high LET damage to that observed from the alpha-particle and Li ion during the
      10B(n, alpha) 7Li reaction. Following irradiation with thermal neutrons from the
      Brookhaven Medical Research Reactor, the effectiveness of the Auger electrons was
      determined by comparing the response of cells incubated with 10BOPP, where damage
      was imparted by the boron neutron capture (BNC) products, to that from Gd-10BOPP,
      with equal concentration of 10B in both solutions. An Auger effectiveness factor
      of approximately 2 was found for the Gd-10BOPP cells. The Auger effectiveness
      observed with Gd strongly suggested that the 10BOPP molecule physiologically
      transported the Gd3+ ion intracellularly where it probably bound to DNA. Others
      have reported that Gd3+ does, in fact, complex with DNA. While depositing less
      energy per interaction than the high LET BNC reaction by-products, Auger electron
      ionization was more effective.

PMID- 9004773
TI  - On the safety of 5-[125I]iodo-2'-deoxyuridine--Preclinical evaluation in swine.
AB  - To increase tumor incorporation and minimize hepatic degradation of radio-IUdR,
      compartmental administration routes are being considered as an alternative to
      intravenous (i.v.) injections. Although there are significant data on the
      biodistribution and some reports on radiotoxicity of i.v.-administered 125IUdR,
      similar results for other routes of delivery are not available. We have
      undertaken a series of experiments intended to examine radiation effects of
      125IUdR after intravesical (3 swine; eight 3 mCi doses at 4-day intervals),
      intracarotid (3 swine; two 10 mCi doses at 2-week intervals), and intra-aortic (5
      swine, single dose of 10 mCi) administration in a swine model. Liver, renal
      functions, and complete blood counts were monitored throughout the duration of
      the experiment. Pharmacokinetics, systemic distribution of radioactivity and
      metabolites were measured. The normal tissue 125IUdR uptake and histology were
      determined after necropsy. No adverse systemic effects were identified. Clinical
      observations, laboratory data, and necropsy results were within normal range.

PMID- 9004774
TI  - 5-[125]iodo-2'-deoxyuridine in the radiotherapy of solid CNS tumors in rats.
AB  - We have been investigating the therapeutic efficacy of the thymidine analog 5
      iodo-2'-deoxyuridine (IUdR) when radiolabeled with the Auger electron emitter
      125I in rats bearing intrathecal (i.t.) or intracerebral (i.c.) 9L gliosarcoma
      solid tumors. [125I]IUdR was infused i.t. (via subarachnoid catheters) or
      intracerebrally over a 5- or 2-day period; equimolar concentrations of [127I]IUdR
      were infused into control animals. Hind-leg paralysis and/or survival were
      followed over time. The results indicate that compared with [127I]IUdR, rats
      bearing intrathecal tumors and infused i.t. with [125I]IUdR showed significant
      prolongation of the onset of median paralysis (15.2 versus 9 days). Similarly,
      the median survival of rats bearing intracerebral tumors and infused i.c. with
      [125I]IUdR was significantly increased (24 versus 17 days). The data substantiate
      the antineoplastic potential of [125I]IUdR and indicate a promising role for this
      radiopharmaceutical in the treatment of CNS cancers.

PMID- 9004775
TI  - Biochemical modulation by 5-fluorouracil and 1-folinic acid of tumor uptake of
      intra-arterial 5-[123I]iodo-2'deoxyuridine in patients with liver metastases from
      colorectal cancer.
AB  - In previous studies we demonstrated a high tumor-targeting value of the 123I
      labeled thymidine analogue 5-iodo-2'-deoxyuridine (IUdR) infused intra-arterially
      in patients with liver metastases from colorectal cancer. In the present study we
      have explored the possibility of enhancing tumor uptake of [123I]IUdR, by
      biochemical modulation with 5-fluorouracil (5-FU) and 1-folinic acid (FA), a drug
      combination known to inhibit thymidylate synthetase in tumor cells. The
      investigation was carried out employing diagnostic imaging doses of [123I]IUdR,
      much lower than possible therapeutic levels. In the baseline study, [123I]IUdR
      was infused into the hepatic artery of patients with inoperable liver metastases
      from colorectal cancer, and a second infusion was performed one week later, after
      intra-arterial administration of 5-FU and FA. The effect was evaluated by
      comparing tumor uptake of [123I]IUdR in the second study with that of the
      baseline study. The average tumor uptake immediately after [123I]IUdR infusion
      was 9.1% ID in the baseline study, increasing to 14.9% ID after pretreatment with
      5-FU and FA. The average enhancement in early tumor uptake of [123I]IUdR induced
      by biochemical modulation was 72%. This enhancement was sustained at 18 and 42
      hours after infusion (stable uptake). The results encourage the pretreatment of
      patients with 5-FU and FA prior to radioiodinated IUdR administration and suggest
      its inclusion in therapeutic protocols employing IUdR labeled with 123I or 125I
      as a source of highly cytotoxic Auger electrons.

PMID- 9004776
TI  - Cell survival after Auger electron emission from stable intracellular indium
      exposed to monochromatic synchrotron radiation.
AB  - The biological effect of Auger electrons emitted from indium in V79 cells was
      investigated. K-shell vacancies were induced by synchrotron x-rays. Two energies,
      100 eV above and below the K-edge of indium, were used. The cell survival for
      controls was similar to that which has been reported by others, with D37 = 4.4
      Gy. Indium-oxine-labelled cells exhibited a survival clearly below that of the
      controls, D37 = 3.2 Gy, but no significant difference in survival between
      irradiations above and below the K-edge could be observed. The explanation is,
      inter alia, that the number of photons interacting with indium atoms incorporated
      into the cell, is small compared with the number of photons interacting with
      other atoms in the cell. The toxicity of indium oxine made it impossible to
      incorporate a sufficient number of indium atoms into the cells to observe a
      difference in this study. However, monoenergetic irradiation above and below the
      K-edge, provides a technique for the investigation of basic biological effects of
      Auger processes.

PMID- 9004777
TI  - Absorbed fraction to the cell nucleus for low energy electrons.
AB  - The absorbed fraction phi to the cell nucleus for low energy electrons (0.5 keV
      50 keV) was evaluated. Distributions of radioactivity within either the nucleus
      (nu) and the cytoplasm (cy), or on the cell membrane (mem) were considered. phi
      was computed as a function of the cell sizes and of the electron energy E. For a
      strictly intranuclear distribution, phi(nu) is close to 1 for very low energy
      values (E < 4 keV), i.e. the energy is totally absorbed in the cell nucleus
      itself. The absorbed fraction decreases when the energy increases and phi(nu)
      becomes less than 0.1 for E > or = 40 keV. For a cell membrane distribution, the
      absorbed fraction remains always less than 0.2. For very low energy electrons (E
      < 6 keV), phi(mem) = 0, due to the fact that the electron falls short to the
      nucleus target. The absorbed fraction is maximum for E ranging from 12 keV to 20
      keV. For higher values of E, phi(mem) decreases when E increases. When
      considering a cytoplasmic distribution, the maximum absorbed fraction phi(cy) is
      obtained for E values ranging from 10 keV to 25 keV (phi(cy max) = 0.27).
      Dosimetric computations at the cellular level show that the absorbed fraction to
      the cell nucleus may have values ranging from 0 to 1, depending on the dimensions
      of the cell, the energy of the emitted electron and on the intracellular
      localization of the Auger emitter.

PMID- 9004778
TI  - Colon-specific prodrugs of 5-radioiodo-2'-deoxyuridine.
AB  - Two glycoside-based prodrugs, 125IUdR-5'-beta-D-glucopyranoside and 125IUdR-5'
      beta-D-galactopyranoside, were synthesized. This selection was dictated by the
      abundance of appropriate enzymes in the GI tract of mice and similar levels of
      beta-D-glycosidases in human and rodent large intestine. Studies to establish the
      ability of colonic microflora to release 125IUdR were conducted in vitro and in
      Swiss Webster mice. Both prodrugs released 125IUdR in the presence of the
      corresponding enzymes or the GI content homogenates in vitro, and in vivo.
      Luminal enzymes in the proximal and distal small intestine in mice degraded less
      than 10% of each prodrug whereas enzymes from the colonic/caecal lumen of mice
      released nearly 100% of 125IUdR. 125IUdR freed by bacterial glycosidases was
      stable in the GI content. No significant amounts of other metabolites or
      deiodination products were observed. Total radioactivity recovered as by-products
      was less than 10%. The efflux of prodrugs from the GI tract after oral
      administration in mice was slow and limited. Unlike 125IUdR, prodrugs were not
      dehalogenated in vivo as indicated by biodistribution and imaging studies.

PMID- 9004779
TI  - Findings of scientific misconduct.

PMID- 9004780
TI  - [The value of symptoms in the diagnosis of peptic ulcer: an approximation to the
      primary care medium].
AB  - GOAL: To evaluate which clinical data are useful to select those patients with
      peptic ulcers in primary care most likely to benefit from complementary studies.
      METHODS: This is a prospective study done on 101 patients evaluated in a period
      of a year in a Primary Care Center. In all patients an endoscopy was done when a
      peptic ulcer was considered a possibility. In all cases a standardized
      questionnaire was completed before endoscopy and the patient evaluated by his
      primary care physician. The final diagnosis was defined according to endoscopy,
      done by expert endoscopists within seven days of the clinical evaluation.
      Statistical analysis was undertaken with SPSS software. RESULTS: An active peptic
      ulcer was found in 45 (44.5%) cases. A high-grade MALT lymphoma was diagnosed in
      one case. Male sex, smoking status, number of cigarettes, smoking-index, and a
      previous history of ulcer complications were significantly associated with the
      diagnosis, as well as severe diurnal or nocturnal pain. Mean age was lower in
      ulcer patients. However no clinical data in individual or combined form did show
      any predictive value. CONCLUSIONS: Clinical data do not permit to obviate
      endoscopy as the key initial procedure to diagnosis, even in primary care.

PMID- 9004781
TI  - [A multicenter clinical trial. Zinc acexamate versus famotidine in the treatment
      of acute duodenal ulcer. Study Group of Zinc acexamate (new UP doses)].
AB  - A multicentric double-blind trial comparing 600 mg/d of Zinc Acexamate (ACZ) and
      40 mg/d of Famotidine (FMT) in the short term treatment of acute duodenal ulcer
      included 199 patients, diagnosed by endoscopy. One-hundred and five patients
      received ACZ and 94 FMT, during four weeks. A clinical control took place at two
      weeks and a second clinical and endoscopic control at the end of the treatment (4
      weeks). Complete cicatrization of the ulcer was observed in 56.5% of patients on
      ACZ and in 69.5% of patients of FMT (N.S.). A reduction of more than 50% of the
      ulcer diameter was recorded in 78.8% of the ACZ group and in 79.9% of the FMT
      group. Alcohol and smoking did not influence the results. Both treatments were
      equally effective in the disappearance of symptoms. The incidence of adverse
      reactions was very low in both groups (< 5%) and no patient dropped from the
      trial for this reason. In conclusion, a dosage of 600 mg/d of ACZ has shown to be
      as effective as 40 mg/d of FMT in the healing of duodenal ulcer.

PMID- 9004783
TI  - Gallbladder dyskinesia in acalculous biliary colic.
AB  - AIMS: To test the hypotheses that: 1) postprandial gallbladder emptying might be
      abnormal in patients with acalculous biliary colic; and 2) that hymecromone, a
      drug that increases bile flow and relaxes biliary muscle might improve symptoms.
      METHODS: Twenty-four women were studied. Twelve patients presented recurrent
      biliary type of pain in the absence of gallstones, and persistence of contrast in
      the gallbladder, 24 hours after an oral cholecystogram, suggesting
      cholesterolosis. Twelve healthy volunteers used as controls had no symptoms and
      the gallbladder was not visible the day after an oral cholecystogram. Gallbladder
      emptying induced by an oral meal was studied with ultrasound in both groups
      before and after the administration of hymecromone. RESULTS: Gallbladder volumes
      were similar in both groups (23 +/- 10 ml vs. 31 +/- 11 ml; NS). Gallbladder
      emptying in the control group was simple exponential (R2 = 0.948 +/- 0.059) with
      a rate of 32 +/- 16 minutes. Gallbladder emptying was bimodal in patients.
      Gallbladder volume increased to 120% in the first 10 minutes, to empty
      exponentially thereafter (R2 = 0.964 +/- 0.040. Rate: 29 +/- 22 minutes). This
      resulted in a marked reduction in gallbladder volume emptied at 40 minutes when
      compared to controls (30% +/- 27% vs. 54% +/- 14%; p = 0.012). Pretreatment of
      controls with hymecromone induced an emptying pattern similar to that of
      patients. In patients, emptying after hymecromone did not change but symptoms
      were improved. CONCLUSIONS: An abnormal emptying pattern of the gallbladder was
      identified in patients with acalculous biliary colic, and hymecromone was partly
      effective to reduce pain, despite a minor effect on gallbladder emptying pattern.

PMID- 9004782
TI  - [Diverticular disease. Our experience].
AB  - The authors herein present their personal experience on the surgical treatment of
      complicated diverticular disease. The series consists of 243 patients seen
      between January 1974 and May 1994. One hundred and fifty nine (65.4%) were
      admitted in an elective and 84 (34.6%) in an emergency setting. Medical therapy
      was efficacious in resolving the clinical symptoms in 133. One hundred and ten
      pts. were treated surgically: 91 (82.7%) underwent a left hemicolectomy (one-step
      surgery), 13 (11.8%) the Hartmann's procedure and 6 (5.4%) a sigmoid resection.
      Between 1974 and 1980, when anastomoses were performed manually and an excluding
      colostomy was the procedure of choice, the reported rate of anastomotic
      dehiscence was 21%. With the technological break-through of mechanical staplers,
      that enabled the performance of colostomies "on demand" such rate decreased to 8%
      and finally to 2%, as reported during 1987-94. The operative mortality, between
      1974-84, of those patients who underwent emergency surgery was 14% and decreased
      to 3% between 1985-94. The operative mortality of patients who underwent elective
      surgery between 1974-84 was 1.3% and decreased to 0% between 1985-1994. The
      authors underline the importance of respecting the surgical indications and the
      proper evaluation of pre-operative parameters aiming at a one-step surgery, that
      reduces both post-operative complications and recovery time.

PMID- 9004785
TI  - [Clinical protocols in digestive system hemorrhage caused by peptic ulcer].

PMID- 9004786
TI  - [Excision of esophageal leiomyoma using videothoracoscopy].
AB  - We report the case of a 57 years old male patient presenting with pyrosis and
      dysphagia. A mid-third esophageal leiomyoma was diagnosed. The tumour was
      resected through a right video-thoracoscopic approach and simultaneous
      intraoperative esophagoscopy was performed. The postoperative course was
      uneventful and six months after surgery neither relapsing symptoms nor radiologic
      pathological findings were observed. We consider that symptomatic leiomyoma is a
      good indication for video-assisted thoracoscopic enucleation. The possible
      postoperative complications (esophageal fistula, esophageal pseudodiverticulum)
      may be minimized by means of an adequate surgical technique.

PMID- 9004784
TI  - [Intrahepatic cholestasis of pregnancy. Maternofetal implications].
AB  - OBJECTIVE: To analyze a group of pregnancies complicated by intrahepatic
      cholestasis in order to favour an early recognition and to decrease maternal and
      fetal morbid-mortality. PATIENTS AND METHODS: Retrospective study of 46
      pregnancies with intrahepatic gravidic cholestasis between 1990-94. We review the
      most relevant epidemiologic, clinical and biological features and the obstetric
      and perinatal results. The study group was compared with 1652 non complicated
      pregnancies (control group) from the same period of time. The statistic
      evaluation was made with t Student and chi 2. RESULTS: The incidence was 0.18%
      (mean age of 27.8 +/- 6.7 years) similar to the control group, and a greater rate
      of primiparity (p < 0.05) and twin pregnancies (p < 0.001). The most frequent
      symptom was pruritus, followed by choluria (23.9%) and signs of cutaneous
      scratching (17.3%). Only 5 patients (10.8%) had jaundice. The GPT was greater
      than 100 U/1 in 29 cases (63.1%) and the GOT in 17 (37%). In 25 pregnancies
      (54.3%) the alkaline phosphatase exceeded 600 U/L and 28 (60.8%) had bilirubin
      normal values. Urinary tract infections (26%) and preterm labor (17.3%) were
      significantly more frequent (p < 0.001) in patients with intrahepatic cholestasis
      of pregnancy, as well as induced labor rate and cesarean section percentages (p <
      0.001). The neonatal prognosis was significantly worse, with 10 preterm babies, 6
      with 5 minutes Apgar score lower than 7, and 3 perinatal deaths. All the patients
      recovered their normal status after delivery. CONCLUSIONS: In intrahepatic
      gravidic cholestasis moderate cytolysis, infrequent jaundice and cholestasis can
      be important. The pregnancies should be considered of high risk, and should be
      managed aggressively as soon as fetal maturity allows it.

PMID- 9004787
TI  - [Paraesophageal hernias in elderly patients. An indication for laparoscopic
      surgery].
AB  - Paraesophageal hernias are uncommon conditions which appear mainly in elderly
      people, frequently associated with sliding hernias or gastric volvulus.
      Considered a high risk pathology, surgical management is preferred to avoid
      serious complications. Due to advanced age and operative risks, a laparoscopic
      approach was performed in the three patients with paraesophageal hernia. In mixed
      hernias, a Nissen or Toupet fundoplication and closure of the hiatal defect was
      carried out. In a case with gastric rotation, reduction of the herniated stomach
      and posterior partial fundoplication with gastropexy was performed. No
      postoperative complications occurred and recovery was satisfactory. Laparoscopic
      management seems to be a good choice for elective treatment of paraesophageal
      hernias in elderly patients.

PMID- 9004788
TI  - [Acute obstruction of the colon secondary to biliary lithiasis].
AB  - Gallstone ileus is an unusual cause of mechanical obstruction of the
      gastrointestinal tract; but obstruction of the colon by a gallstone is an even
      more rare event, and there are few references in the literature. We describe the
      cases of two elderly women who were admitted to the Emergency Service with a
      mechanical obstruction of the colon and air in the biliary tract. A barium-enema
      examination showed the presence of a foreign body in the sigmoid colon; this was
      found to be a gallstone in a subsequent colonoscopy in one of the patients; a
      precise preoperative diagnosis was not possible in the other. In both cases the
      obstruction was caused by a gallstone impacted in the sigmoid colon and a
      cholecystocolonic fistula was evident in a postoperative barium enema
      examination. Correction of the obstruction is the main objective of initial
      treatment. The repair of the fistula can be performed at the same time or at a
      later date.

PMID- 9004790
TI  - [Hepatitis and furosemide].

PMID- 9004789
TI  - [Intrahepatic cholestasis of pregnancy. A benign disease?].
AB  - Intrahepatic cholestasis of pregnancy is a relatively common disease. It has an
      unknown etiology and may have a recurrent pattern. It commonly occurs in the 2nd
      3rd trimester and characteristically presents with pruritus, jaundice and
      abnormal liver function tests. There is also an increased risk of preterm
      delivery and of cesarean section. Both maternal and neonatal prognosis is
      generally good. We describe a case of intrahepatic cholestasis of pregnancy with
      an atypical presentation and outcome. Our patient presented with acute renal and
      hepatic failure with hepatic encephalopathy, DIC and hypertension which was the
      cause of the fetal death in the third trimester of the pregnancy.

PMID- 9004791
TI  - [A new test for the diagnosis of anismus: dynamic endoanal echography].

PMID- 9004792
TI  - [Toxic hepatitis caused by aceclofenac].

PMID- 9004793
TI  - [Serum laminin in chronic alcoholic liver disease: its value in the estimation of
      the degree of fibrosis].
AB  - AIM: To determine the clinical and prognostic value of serum laminin in chronic
      alcoholic liver disease and to discern whether laminin, alone or in combination
      with serum N-terminal type III collagen propeptide, and/or biochemical
      parameters, is useful in estimating the histomorphometrically determined amount
      of fibrosis. STUDY DESIGN: Prospective. PATIENTS: 121 (80 of them cirrhotics),
      107 followed up for a variable periods ranging from 1 to 1440 days. RESULTS:
      Serum laminin was higher in cirrhotic patients belonging to Child's C group and,
      in cirrhotic patients, it significantly correlated with Pugh's score (r = 0.32, p
      < 0.01), prothrombin activity (r = 0.23, p < 0.05), serum albumin (r = -0.35, p <
      0.001) and bilirubin (r = 0.30, p < 0.01), and also with the degree of fibrosis
      (r = 0.49, p < 0.001). Serum laminin over 3.5 U/ml were associated to higher
      mortality rates in the total population (Log rank test = 4.9, p = 0.022), but not
      in cirrhotics. Stepwise multiple regression analysis showed that laminin is
      useless in the estimation of liver fibrosis in cirrhotics, although in non
      cirrhotic alcoholics, serum laminin together with alkaline phosphatase and GGT
      roughly estimates the amount of liver fibrosis (r = 0.72, p < 0.001, standard
      error = 7.29). CONCLUSIONS: Laminin is not useful in estimating the total amount
      of fibrosis neither in prognostic assessment of cirrhotics. However, serum
      laminin-values over 3.5 U/ml were associated with higher mortality rates in
      patients with chronic alcoholic liver disease, and serum laminin together with
      alkaline phosphatase and GGT correlated with the amount of fibrosis in the non
      cirrhotic subgroup.

PMID- 9004794
TI  - [Analysis of surgery of gastroesophageal reflux by laparotomy and laparoscopy
      approach].
AB  - The development of the laparoscopic surgery has allowed its use in the treatment
      of gastroesophageal reflux. PATIENTS AND METHODS: We have reviewed the results
      and follow-up of 30 patients treated with open procedure (group A) and 30
      patients with laparoscopic surgery (group B). The most frequent indication for
      surgery was failure of medical therapy and the Nissen fundoplication was the
      method most commonly used. RESULTS: The average surgical time was shorter in
      group A (66 minutes) than in group B (140 minutes). Intraoperative complications
      were: in group A, 2 patients with splenic injury; in group B, 3 patients required
      conversion to the open procedure (pneumothorax, gastric perforation, technical
      problems) and 1 patient with pneumothorax which didn't require conversion.
      Postoperative morbidity and mortality occurred in 20% (26% group A, 13% group B);
      the most common complications were: respiratory (4 patients), gas bloat syndrome
      (2 patients) and esophageal perforation (1 patient). At follow-up we observed
      complete heartburn relief in 95%, 4 patients in group A had mild dysphagia, 3
      patients with recurrent hiatal hernia (2 in group A and 1 in group B) and 2
      patients required reintervention in group A (intestinal occlusion caused by
      adherence and laparotomic hernia). Mortality occurred in a patient with
      esophageal perforation in group B. CONCLUSIONS: Treatment for gastroesophageal
      reflux is feasible with similar effectiveness with open and laparoscopic
      procedures. The results are advantageous with the laparoscopic procedure relative
      to postoperative morbidity and follow-up.

PMID- 9004795
TI  - [Effect of indomethacin on the secretion of pepsinogen in isolated human cells in
      vitro].
AB  - The effects of indomethacin on pepsinogen secretion were studied in isolated
      human peptic cells prepared from endoscopically obtained biopsies after
      collagenase digestion, mechanical disruption and percoll gradient centrifugation.
      Low concentrations of indomethacin (10(-8)-10(-10) M) stimulated basal pepsinogen
      secretion. Higher doses of indomethacin (10(-5)-10(-6) M) potentiated histamine
      (10(-4) M) and db-cAMP (10(-4) M)-stimulated pepsinogen secretion without
      affecting acetylcholine (10(-6) M) and CCK-8-stimulated pepsinogen secretion or
      cell vitality. Increase of pepsinogen secretion was dependent on extracellular
      calcium because potentiation was abolished by calcium depletion of the medium. We
      conclude that indomethacin potentiates basal and secretagogue-stimulated
      pepsinogen secretion by dispersed human peptic cells and this might be an
      additional mechanism of NSAID-induced gastric injury. This potentiation effect is
      regulated by calcium and independent of endogenous prostaglandin inhibition.

PMID- 9004796
TI  - [Breath test in the diagnosis of Helicobacter pylori infection: concordance with
      histological methods and correlation with anatomopathological lesions of the
      gastric mucosa].
AB  - PURPOSE: To study the concordance between 13C-urea breath test and histology in
      the diagnosis of Helicobacter pylori infection, and to evaluate whether there is
      a correlation between breath test values and histologic lesions of the gastric
      mucosa. METHODS: Sixty-nine patients with duodenal ulcer were prospectively
      studied. An endoscopy with biopsy samples (H&E stain) taken from the antrum and
      body was performed, and a 13C-urea breath test (measuring 13C difference: delta
      13CO2) was also done. Both procedures were repeated one month after completing
      therapy ["classic" triple therapy (n = 28), and omeprazole+amoxycillin (n = 41)].
      Eradication was defined as the absence of H. pylori both by histological and
      breath test methods. RESULTS: At the beginning of the study, 94.2% of patients (n
      = 65) were H. pylori positive by histological methods, and 98.6% (n = 68) were
      positive by the breath test (ratio of positive agreement = 0.96). Kappa for H.
      pylori diagnosis after therapy was 0.83 (95% CI: 0.69-0.96). A correlation
      between delta 13CO2 and histologic lesions was observed, both in the antrum at
      before treatment (Spearman coef = 0.34; p = 0.007) and after therapy in both the
      gastric antrum (0.63; p < 0.001) and body (0.35; p = 0.005). A significant
      difference was observed when comparing mean delta 13CO2 in patients with
      different degrees of histologic gastritis, both before treatment (antrum: W
      Kruskal-Wallis = 6; p < 0.05) and after therapy (antrum: W = 17; p < 0.001; body:
      W = 10; p < 0.05). CONCLUSION: A high concordance was observed between the 13C
      urea breath test and histology in the diagnosis of H. pylori infection. A
      correlation exists between breath test values and histologic lesions of the
      gastric mucosa.

PMID- 9004797
TI  - Endoscopic anal dilatation for fissure-in-ano: a new outpatient treatment
      modality.
AB  - We describe a new therapeutic procedure for fissure-in-ano, endoscopic anal
      dilatation. Anal dilatation is performed with a two-valved anoscope under local
      anesthesia in an ambulatory setting. We report our results using this technique
      in 62 patients after a mean follow-up of 19 months (range: 12-24 months). Thirty
      days after the procedure, 55 patients (93%) were symptom-free, whereas 3 of them
      (4.8%) failed to improve. After nineteen months, one patient out of 47 in follow
      up had a recurrence. No bleeding, discharge or defects of continence, either
      transient or permanent, were noted. The results of endoscopic anal dilatation are
      comparable with those of lateral sphincterotomy, can be achieved at a lower
      complication rate, with only minor and temporary complications, and performed by
      physicians with no specific surgical training.

PMID- 9004798
TI  - [Shunt surgery versus disconnection in portal hypertension. A comparative study].
AB  - Controversy remains about the best treatment for patients with esophagogastric
      variceal bleeding. In spite of different therapeutic alternatives and recent
      progress, such as liver transplantation of TIPS, many patients will finally be
      treated by standard surgery. With the aim to know the results of surgery in
      shunting vs non-shunting procedures, we have analyzed a recent and consecutive
      series of 68 cirrhotics patients operated on for variceal hemorrhage. According
      to the surgical technique there were three groups: I) 30 patients underwent a
      total portacaval shunt; II) 18 cases with an azygosportal disconnection; III) 20
      patients with a partial portacaval shunt (8-10 mm H-portacaval PTFE graft). All
      groups were homogeneous considering age, sex etiology, Child-Pugh grade and
      timing of surgery (elective vs urgent). The complications and mortality rates
      were similar for the three groups. The overall operative mortality was 10%, and
      5% in selected cases (Child-Pugh A-B, non urgent cases). With a follow-up for I,
      II and III group of 47, 44 and 27 months respectively, chronic encephalopathy
      have been seen in 61%, 15% and 15% respectively (p < .05). No patient in group I
      has rebled, and only one case in the II and III groups had a recurrence of
      hemorrhage. The actuarial three years survival was 76%, 86% and 85% (p NS), and
      the five year survival was 41% vs 86% for the groups I and II respectively (p <
      .05). In conclusion, in selected cases, surgery gives excellent immediate and
      long term results. In patients with variceal bleeding and failure of first line
      treatments, such as sclerosis or pharmacology, the partial H-portacaval shunt and
      non-shunting procedures are good alternatives, with low incidence of rebleeding
      and chronic encephalopathy.

PMID- 9004799
TI  - [Diarrhea in patients with AIDS].

PMID- 9004800
TI  - [The defense of the esophageal mucosa].

PMID- 9004801
TI  - [Acute abdomen caused by jejunal perforation as a clinical presentation of MEN-1
      syndrome].
AB  - We present a case of acute abdomen due to a jejunal perforation. The final
      diagnosis was concluded a multiple endocrine neoplasia type I. In the literature
      reviewed, no similar clinical presentation was found. We review the diagnostic
      sequence and the management of these patients.

PMID- 9004802
TI  - [Menetrier's disease suspected by ultrasonography].
AB  - Menetrier's disease was suspected in a patient during transcutaneous ultrasound
      by the finding of an important thickening of the mucosa with normality of
      submucosal, muscular and serous layers. The description of the ultrasound aspect
      of this disease is very uncommon, specially in adults.

PMID- 9004804
TI  - [Obstructive jaundice as a presentation form of bronchogenic small cell
      carcinoma].
AB  - We report a patient having a non-diagnosed small cell lung cancer, presenting
      with a clinical picture comprising emaciation, hepatomegaly, progressive
      jaundice, bilirubinuria and clay-colored stools. Computed tomography showed
      intrahepatic and extrahepatic biliary duct dilatation. The cause was compression
      of the common bile duct by metastatic enlarged lymph nodes in the porta hepatis.
      Clinical suspicion arose because of a mass found on the chest X-ray film and a
      positive cytologic sputum examination. The definitive diagnosis was obtained by
      bronchoscopy and biopsy.

PMID- 9004803
TI  - [Cytomegalovirus infection as a cause of granulomatous hepatitis in an
      immunocompetent patient].
AB  - We report the case of an immunocompetent young male with granulomatous hepatitis
      in relation with cytomegalovirus. We discuss clinical and histopathological
      features of hepatitis by cytomegalovirus in immunocompetent and immunosuppressed
      patients.

PMID- 9004805
TI  - [Use of sennosides A + B in the preparation of the colon for endoscopy].

PMID- 9004806
TI  - [Complications associated with the use of an overtube in endoscopic ligation of
      esophageal varices].

PMID- 9004807
TI  - [Pancreas divisum: a controversial cause of acute pancreatitis?].

PMID- 9004809
TI  - [Transesophageal echocardiography and risk factors for embolism].
AB  - Echocardiography is the main diagnostic tool for thromboembolic risk evaluation
      in patients with atrial fibrillation (AF). Transthoracic echocardiography (TTE)
      has low sensitivity and specificity in thrombus detection, especially in left
      atrium appendage; on the other hand the transesophageal approach (TEE) provides
      information about thrombi located anywhere. In recent years, large trials on
      thromboembolic risk in AF have given strong value to echocardiographic risk
      factors such as left atrial enlargement and left ventricular dysfunction, well
      detected by TTE. Transesophaged echocardiography can be considered the best
      technique to study factors even more closely correlated to thromboembolic risk,
      such as spontaneous echocontrast or left atrium appendage abnormalities both
      anatomical (enlargement and malformations) or functional (low peak velocity).
      Preliminary data from new trials, like SPAF III and FASTER, confirm this fact. On
      the other hand, TEE permits the study of thoracic aorta and atheromasic lesions,
      which can be considered additional direct (ulcerated plaques) or generic
      thrombotic risks.

PMID- 9004808
TI  - [Large trials in the secondary prevention of stroke].
AB  - To date, no drug has been demonstrated as efficacious in the treatment of acute
      ischemic stroke. Therefore, primary and secondary prevention play a fundamental
      role. Besides adequate control of risk factors, trials and meta-analyses have
      demonstrated that both medical and surgical therapy are effective in secondary
      prevention of stroke. In patients with atherothrombotic transient ischemic attack
      (TIA) or minor stroke and carotid stenosis > 70%, surgical therapy
      (endarterectomy) is the treatment of choice, while antiplatelet drugs are the
      elective treatment in the case of stenosis < 70%. Acetylsalicylic acid is the
      first choice medical treatment, but the optimal dosage is still a matter of
      debate. Ticlopidine has an efficacy similar to that of aspirin, but shows a
      certain number of side effects; recently a European study has shown the efficacy
      of dipyridamole, and the superiority of the combination dipyridamole-aspirin vs
      low-dose aspirin. In the secondary prevention of cardioembolic stroke, oral
      anticoagulants have higher efficacy than antiplatelet drugs, at least in selected
      groups of patients.

PMID- 9004810
TI  - [Therapeutic objectives in the subacute phase after stroke].
AB  - The aim of this study was to identify the most appropriate clinical management of
      the subacute stage after stroke, in order to reduce mortality and control
      disability following cerebrovascular disease. Data were collected from
      international journals, books and guidelines written by accredited agencies and
      scientific societies. Reviews and clinical investigations written by authors
      operating in stroke assistance facilities have been selected among those
      submitted to accredited scientific journals, spontaneously or upon request by
      editors of specific sections or supplements. Furthermore, the guidelines proposed
      by either scientific or lay associations have been considered. The following
      elements have been considered: i) prevention of morbidity and treatment of
      complications in the subacute phase; ii) identification of uncommon stroke
      causative factors in order to prevent recurrent events; iii) prognosis of
      survival and disability; iv) activation of rehabilitation. Results show that a
      careful evaluation of stroke etiology and the direct management of
      cerebrovascular problems by specialized utilities bring about an increase in
      survival rate and reduce disability. The treatment of complications, the
      evaluation of recovery capacity and the accomplishment of rehabilitation
      strategies, based on accredited criteria of organization, allow an increase in
      the efficiency of assistance facilities. Involvement of the family has a positive
      influence on autonomy. In conclusion, the qualified management of stroke patients
      can reduce mortality and disability, even if there is still no effective therapy,
      capable of reducing cerebral damage.

PMID- 9004812
TI  - [Progress in hypocholesterolemic therapy in the prevention of recurrent
      infarction].
AB  - The role of the hypocholesterolemic therapy in reinfarction prevention is
      evaluated using data from observational and secondary prevention studies. Even
      though survival after myocardial infarction is largely determined by the
      extension of the necrotic lesion, hypercholesterolemia remains an important risk
      factor for new vascular events. A total cholesterol reduction < 200 mg/dL (or
      even better LDL cholesterol < 100 mg/dL) in these patients is associated within
      few years with a significant reduction of both clinical events and total
      mortality. The reduction of clinical events is obtained in a relatively short
      period of time thus suggesting that plasma cholesterol reduction induces quite
      rapidly some modifications of the natural history of the atherosclerotic plaques,
      this effect being more relevant in vulnerable or unstable lesions that are
      responsible for most of the clinical events. These observations show that after
      myocardial infarction it is useful to reduce cholesterol < 200 mg/dL also with
      the use of drugs.

PMID- 9004811
TI  - [Coronary risk stratification and aspects of decision making after infarction].
AB  - The prognosis of myocardial infarction has considerably and favourably changed
      over the last decades thanks to new procedures in the hospital and post-discharge
      management. The identification of high-risk patients exposed to recurrent
      coronary events allows more appropriate treatment of these subjects and
      significantly contributes to the observed improvement in the general prognosis.
      In this short review, we examine different procedures for prognostic assessment
      in myocardial infarction and discuss a strategy for a favourable cost/benefit
      ratio in their utilization.

PMID- 9004813
TI  - [Integration of therapeutic options and the candidates for treatment: the ABC of
      the post-infarction period].
AB  - Acute myocardial infarction, major cause of death in Western society, has been
      the focus of many clinical investigations over the past decade. As the result of
      randomized trials involving hundreds of thousands of infarct patients worldwide,
      the life-saving potential of several pharmacologic interventions has been
      validated, and the usefulness of other commonly used treatments has been
      disproven or brought into question. Much of the innovative therapy has been
      targeted toward limiting myocardial damage by eradicating the occlusive thrombus
      or otherwise restoring flow through the infarct-related artery, reducing oxygen
      demands in the injured ventricle, and altering vascular dynamics to limit the
      process of ventricular remodeling. Data have accumulated showing substantially
      lower mortality of acute myocardial infarction with simple pharmacological
      interventions such as intravenous thrombolytic therapy, aspirin, beta-blockers
      and ACE-inhibitors. In particular, ACE-inhibitors have recently proven to be
      effective in infarcted patients, especially in high-risk subjects with acute
      anterior infarction not treated with thrombolytic agents or patients with left
      ventricular dysfunction. ACE-inhibitors may limit the process of ventricular
      remodeling after a large infarction, lessening the risk of sudden death and heart
      failure. Intravenous heparin has a role in maintaining patency of infarct-related
      vessel after rt-PA, and it seems that this combination offers some benefits with
      respect to streptokinase plus subcutaneous heparin. Recent studies have also
      demonstrated the importance of lipid-lowering agents for secondary prevention
      after myocardial infarction. Several previously recommended therapies (routine
      intravenous lidocaine, calcium channel blockers, magnesium, nitrates) have not
      been proven to be life-saving.

PMID- 9004814
TI  - [Secondary prevention of myocardial ischemia. From theory to clinical reality:
      preliminary results of the EUROASPIRE study in Italy. European Action on
      Secondary Prevention through Intervention to Reduce Events].
AB  - EUROASPIRE study has been carried out in 9 European countries with the aim of
      assessing coronary risk factors in high-risk patients admitted to hospital to
      undergo coronary revascularization procedures (coronary angioplasty or coronary
      artery bypass grafting) or because of angina or myocardial infarction. The
      results of the initial stage of the study in Italy, investigating the data from
      691 hospital medical records, showed that management of risk factors in these
      patients was inferior than expected. In particular, the prevalence of
      hyperlipidaemia (63%), hypertension (40%) and diabetes (27%) was remarkably high.
      These results suggest that there is still a need for secondary prevention of
      coronary heart disease.

PMID- 9004815
TI  - [Prevention of thromboembolism in atrial fibrillation of non-valvular etiology].
AB  - Atrial fibrillation is an independent risk factor for cerebral and systemic
      embolism. The risk increases with the patient's age and the presence of other
      risk factors: hypertension, diabetes, cardiac failure, prior transient ischemic
      attacks or embolic stroke. Risk stratification is of essential importance to
      allow the choice of the most suitable prophylaxis with antithrombotic drugs for
      the individual patient. On the basis of the results of controlled clinical
      trials, it is possible to suggest the following guidelines: a) in patients at low
      risk (< 65 years, with no other risk factor) the drug of first choice should be
      acetylsalicylic acid; b) in patients at high risk (> 65 years, with one or more
      risk factors) the drugs of first choice are oral anticoagulants, given at doses
      that prolong the prothrombin time to INR values of 2-3; c) in patients at high
      risk with contraindications to oral anticoagulants, acetylsalicylic acid or
      indobufen (shown to be as effective as oral anticoagulants in patients with prior
      transient ischemic attacks or stroke) should be considered.

PMID- 9004816
TI  - [Anticoagulant therapy in patients with atrial fibrillation: the experience of
      the Centers of Surveillance. Study group of the "Italian Study on Complications
      of Oral Anticoagulant Therapy" (ISCOAT)].
AB  - The present study evaluated the anticoagulant course of 580 patients (21% of the
      total number of patients, 317 males, half of them aged > 70 years) with atrial
      fibrillation (AF) enrolled in the ISCOAT study. During the 469 patient-years of
      follow-up 35 bleeding (7.6%; 2 fatal, 8 major) and 17 thrombotic events (3.6%)
      occurred. Bleeding was more frequent when AF was associated with other
      cardiovascular diseases (9.8%) and occurred even if the anticoagulation level was
      low (9% when INR was < 2), probably due to the presence of individual risk
      factors. As expected, thrombotic events were also more frequent when INR level
      was < 2. We conclude that in patients with AF the recommended therapeutic range
      seems to be INR 2-3, since this range proved to be safe and more effective than
      lower anticoagulation levels.

PMID- 9004818
TI  - [Natural course and physiopathology of ascites in the cirrhotic patient].
AB  - Ascites formation in cirrhosis results from the interaction of "local" and
      "systemic" pathogenetic factors. Among local factors, post-sinusoidal portal
      hypertension plays the most important role, while the main systemic event is
      renal sodium retention. The latter precedes ascites formation and leads to plasma
      volume expansion. Many factors are responsible for renal sodium retention, but
      secondary hyperaldosteronism and reduced renal perfusion prevail. The events
      promoting the onset of sodium retention are far from being clarified. However,
      there is evidence that the main afferent mechanism is represented by the
      "effective" hypovolemia secondary to splanchnic venous vasodilation, due to
      portal hypertension, and reduced peripheral vascular resistance, which becomes
      evident in the advanced stage of the disease. Systemic hemodynamic abnormalities
      are responsible for the progressive reduction of renal perfusion, which ends in
      the hepatorenal syndrome. The appearance of ascites is a crucial event in the
      natural history of cirrhosis and has a negative prognostic meaning. In fact,
      ascites appears when pathogenetic factors, such as liver function abnormalities,
      portal and systemic hemodynamics, and renal function, have reached a critical
      threshold severity. Second, ascites itself induces additional complications,
      closely linked to its presence, such as spontaneous bacterial peritonitis,
      restrictive respiratory failure, or rupture of abdominal hernias. Finally,
      ascites implies pharmacological or invasive treatment which can lead to further
      morbidity or even to death.

PMID- 9004819
TI  - [Physiopathologic basis of medical therapy of portal hypertension in cirrhosis].
AB  - The in-depth study of the pathophysiology of portal hypertension is the basis for
      a correct medical treatment. The backward-flow theory of portal hypertension
      stresses the importance of increased hepatic vascular resistance, while the
      forward-flow theory of portal hypertension underscores generalized vasodilation,
      the hyperdynamic circulation and increased portal inflow. The role of expanded
      plasma volume has been emphasized in recent studies. The aim of drug therapy is
      to normalize each one of these components. Vasoconstrictor agents, i.e.
      vasopressin, triglycyl-lysin-vasopressin, non selective beta-blockers,
      somatostatin and octreotide, try to normalize the increased portal inflow and to
      decrease porto-collateral blood flow. Venous vasodilators, e.g. nitrates, mainly
      act by decreasing portal blood outflow resistance. Spironolactone has been
      proposed to decrease plasma volume. The use of a combination of a vasoconstrictor
      agent and a vasodilator or spironolactone has been proposed to increase the
      efficacy of medical treatment.

PMID- 9004817
TI  - [Viral liver cirrhosis: natural course, pathogenesis and clinical implications of
      the complications].
AB  - The role of hepatitis B virus (HBV) and hepatitis C virus (HCV) as a major cause
      of chronic liver disease is now accepted worldwide. This study was aimed at
      evaluating the natural history of the disease in patients with virus-induced
      chronic active hepatitis or cirrhosis, and the influence played by age, sex and
      etiology, liver function tests and by the occurrence of different complications.
      We retrospectively examined the clinical records of 506 inpatients: 194 were
      affected by chronic active hepatitis (125 males, 69 females, mean age 45 +/- 11
      years, 146 HCV- and 48 HBV-related), and 312 by cirrhosis without clinical
      evidence of portal hypertension (178 males, 134 females, mean age 53 +/- 9 years,
      249 HCV- and 63 HBV-related). The occurrence of cirrhosis in the chronic active
      hepatitis group was then calculated, together with the occurrence of
      complications and the cumulative mortality rate of established cirrhosis. During
      follow-up 93 patients with chronic hepatitis developed cirrhosis. The cumulative
      probability of developing cirrhosis in this group was 6.64% at 5 years, 56.1% at
      10 years and 86.8% at 15 years. These patients were therefore included in the
      cirrhosis group for the final analysis, so that a total of 405 cirrhotic patients
      were evaluated: these patients had a cumulative survival rate of 99.1% at 5,
      76.8% at 10 and 49.4% at 15 years. Comparing the age-adjusted death rate of our
      patients with the general Italian population, we observed that in patients with
      liver cirrhosis it was 3.14 and 2.84 times higher in men and women, respectively.
      Bilirubin was an independent indicator of survival. Several complications, such
      as esophageal varices, ascites, jaundice, hemorrhage, hepatic encephalopathy and
      hepatocellular carcinoma significantly reduced the survival rate and were
      indicated as major complications, while thrombocytopenia, cholelithiasis and
      diabetes did not affect survival and thus were called minor complications.
      Incidence of hepatocellular carcinoma was very high especially in males, without
      correlation with etiology. In conclusion, the progression of virus-induced
      chronic active hepatitis to cirrhosis is not influenced by sex and etiology.
      Similarly, the different etiology does not modify the natural history of
      cirrhosis while the occurrence of one or more major complications significantly
      shortens survival. The longer survival rate observed in patients with cirrhosis
      included in this study is probably due to the selective inclusion of patients
      with early disease and no evidence of portal hypertension.

PMID- 9004820
TI  - [Intrahepatic cholestasis in chronic liver disease].
AB  - Cholestasis syndromes are characterized by a reflux of compounds usually excreted
      with bile. ATP dependent carriers and cytoskeleton proteins guarantee
      physiological bile flux. There are several clinical conditions in which this
      system is affected. Intrahepatic cholestasis is characterized by damage to
      hepatocytes or intrahepatic bile ducts. Primary biliary cirrhosis and primary
      sclerosing cholangitis represent examples of cholestatic chronic liver disease.
      The pathogenesis of these two conditions seems to be mediated by immunological
      reactions. Moreover, hepatitis viruses are able to induce cholestasis.

PMID- 9004822
TI  - [Gene therapy in cardiovascular medicine: reality or fantasy?].
AB  - Since the discovery of DNA and the genetic code the main goals of molecular
      medicine have been: to understand the genetic basis of diseases, and to develop
      strategies capable of providing long-term cure. In the last 2 decades
      methodological progress has made it technically feasible to pursue both these
      goals. In its classical conception gene therapy consists in the introduction of
      genes into somatic cells in order to correct a specific genetic defect or to
      provide cells with a new function which will ultimately result to be advantageous
      for the patient. These strategies have been proposed for the treatment of
      numerous diseases, both hereditary, mono- or polygenic, and acquired in nature.
      The purpose of this review is to discuss the problems inherent in gene therapy,
      currently pursued strategies and future clinical perspectives.

PMID- 9004821
TI  - [Epidemiology and therapy of atrial fibrillation].
AB  - Atrial fibrillation (AF) is the most common supraventricular arrhythmia in the
      Western world and its prevalence increases with age. The objectives of the
      pharmacologic treatment of AF are mainly three: to restore sinus rhythm, to
      maintain sinus rhythm, and to control ventricular rate during AF. Class 1C
      antiarrhythmic drugs (propafenone, flecainide) have been demonstrated to be the
      most effective drugs in restoring sinus rhythm with low risk/benefit and
      cost/benefit ratios and percentage efficacy rate between 50% and 60%. The long
      term efficacy of antiarrhythmic therapy for preventing AF recurrences is far from
      ideal. Different studies have reported unsatisfactory results with class 1C,
      class III (sotalol) and class 1A (quinidine, diisopyramide) antiarrhythmic drugs.
      Calcium channel blockers (diltiazem, verapamil) alone or in combination with
      digitalis are the drugs of choice in ventricular rate control. New pharmacologic
      approaches may be hypothesized based on the experimental evidence of 5-hydroxy
      triptamine receptors in human atria. Non pharmacologic attempts introduced for AF
      therapy include: pacemaker implantation, catheter ablation, surgical procedures,
      internal defibrillation. Atrial fibrillation in patients with tachycardia
      bradycardia syndrome is an important indication for permanent pacing. With the
      advent of dual chamber stimulation it has become apparent that atrioventricular
      sequential pacing may be superior to VVI pacing in patients with sick sinus
      syndrome where it may prevent the development of chronic AF. Catheter ablation of
      atrioventricular node is an accepted approach in patients with drug refractory
      AF, in patients with sick sinus syndrome where pacemaker therapy failed to
      prevent paroxysmal AF, or in patients with ICD in order to avoid inappropriate DC
      shock. Surgical interventions for AF aim at maintaining sinus rhythm by confining
      the arrhythmia within the left atrium (left atrial isolation technique) or to
      both left and right atrium (corridor technique). Another procedure (maze)
      consists of multiple incisions in the right and left atrium. Recently internal
      low energy cardioversion has been demonstrated to be effective in treating AF in
      animal models, and initial clinical studies have shown it can be useful in
      cardioverting chronic AF in humans as well, suggesting the potential usefulness
      of an implantable cardioversion device in clinical practice.

PMID- 9004823
TI  - [Hypertension and depression].

PMID- 9004826
TI  - [Depressive disorders and myocardial infarction].

PMID- 9004825
TI  - [Depression and cardiomyopathies].

PMID- 9004824
TI  - [Arterial hypertension and depression].

PMID- 9004827
TI  - [Therapy of arterial hypertension: benefits, costs, challenges].
AB  - For more than 30 years the benefits of antihypertensive therapy have been
      assessed by randomized trials measuring cardiovascular events. Even greater
      benefits are found if prevention of congestive heart failure, left ventricular
      hypertrophy, and progression to more severe hypertension are considered.
      Quantifying the benefits in order to calculate cost-effectiveness of treatment is
      not easy, however. Taking absolute risk and absolute benefit as a guide to
      treatment decision, though an important approach, may result in limiting therapy
      to elderly and complicated hypertensives only. Furthermore randomized trials,
      whose duration is necessarily short, are likely to underestimate treatment
      benefits. An alternative is the actuarial approach, by which treatment benefits
      are calculated from the actuarial data showing the reduction in life expectancy
      associated with any given blood pressure increase. The cost of antihypertensive
      therapy per year of life gained, as calculated by the actuarial approach, is much
      lower than the cost calculated on the basis of the outcomes of randomized trials.
      In an uncertain area such as that of cost-effectiveness evaluation, it is
      important that both approaches be brought to the consideration of physicians,
      patients, politicians, and officers of national health systems.

PMID- 9004828
TI  - [Clinical pharmacology of leucotriene inhibitors].
AB  - Leukotrienes have been demonstrated to play an important role as mediators of
      many pathophysiologic alterations of asthma. Pharmaceutical companies have thus
      promode many efforts to synthesize new drugs with inhibitory activity on 5
      lypoxygenase or with functional antagonism on cystenyl leukotriene receptors.
      Several compounds have been studied in humans, and some of them should soon be on
      the market. One of these compounds, ICI 204,219 ("accolate"), a receptor
      antagonist active by the oral route, has been proven capable of preventing
      bronchoconstriction induced by several stimuli (allergen, exercise, cold air,
      etc.) and of improving symptoms and lung function in spontaneous asthma. This
      effect augments the bronchodilation induced by inhaled beta 2-agonists. On the
      other hand, no relevant side effects have been reported. However,
      antiinflammatory properties of this compound must be demonstrated. This new
      category of antiasthmatic drugs should be recommended for mild-to-moderate
      asthma, although future studies might demonstrate their efficacy in potentiating
      or substituting inhaled steroids.

PMID- 9004829
TI  - [Leukotrienes: their significance in the pathogenesis of asthma].
AB  - Cysteinyl leukotrienes (cys-LT) are potent spasmogenic agents, increase markedly
      vascular permeability and mucus secretion and promote intense recruitment, with
      activation, of inflammatory cells into the airways, increasing bronchial
      responsiveness. An augmented release of cys-LT from bronchopulmonary tissues has
      been demonstrated in spontaneous asthma and in many obstructive reactions to
      allergic and non-allergic stimuli. Finally some cys-LT antagonists and LT
      synthesis inhibitors have shown remarkable acute anti-reactive activity and good
      clinical efficacy. All these findings point to an important pathogenetic role of
      cys-LT in bronchial asthma.

PMID- 9004830
TI  - [Anti-leukotriene agents: rationale for and prospects of use].
AB  - Leukotrienes (LT) are synthesized from arachidonic acid by several enzymes such
      as phospholipase A2, 5-lipoxygenase, LTC4 synthase, as a consequence of a wide
      range of inflammatory stimuli. Leukotrienes seem to play a pivotal role in the
      maintenance of the inflammatory processes as they exert numerous biological
      activities, i.e. chemotactic action on polymorphonuclear cells, bronchospastic
      action, vasodilator and secretagogue effects. Thus, the inhibition of LT activity
      may result in antiinflammatory action. Several compounds capable of blocking
      either LT synthesis or LT receptors have recently been developed and clinically
      tested in different experimental models. In particular, encouraging results have
      been obtained in the asthma model, but interesting clinical observations have
      also been performed in psoriasis, ulcerative colitis and rheumatoid arthritis.
      Although further studies and optimization of this kind of treatment are required,
      a possible clinical role of LT antagonists as antiinflammatory therapy for
      selected diseases may be envisaged.

PMID- 9004831
TI  - [Diagnostic approach to the patient with stroke].
AB  - In the case of a patient with sudden-onset focal neurological deficit, clinicians
      must answer three fundamental questions: is it a stroke? is it ischemia or
      hemorrhage? and what kind of ischemic stroke is it? Clinical information (i.e.,
      history and examination) is available in any situation, and its role in answering
      these questions is extremely important, even though certainty can only be
      achieved from instrumental diagnostic tools. In fact, when diagnosis is based on
      properly designed clinical criteria, the percentage of mistakes is quite low.
      Clinical methods are still the best way to orient topographic and etiologic
      diagnosis, as well as estimate prognosis. In addition, time might be saved if
      randomization in clinical trials were performed using clinical methods before
      initiating complex investigations.

PMID- 9004833
TI  - [Retroperitoneal schwannoma: report of a clinical case and review of the
      literature].
AB  - The retroperitoneal localization of a schwannoma or neurilemmoma undoubtedly
      represents an unusual occurrence (0.5-0.7% of all sites); this data, together
      with the absence of a typical clinical picture and the lack of peculiar
      instrumental signs, make a preoperative diagnosis of this lesion really hard to
      ascertain. In this paper, on the basis of a case report successfully treated, the
      Authors review the literature analysing current diagnostic and therapeutic work
      up, mainly emphasizing controversies in determining a proper preoperative
      diagnosis among all retroperitoneal tumours.

PMID- 9004832
TI  - [Neurovascular implications in total meso-rectal excisions. A prospective study
      of sexual function after surgery for rectal cancer].
AB  - Total mesorectal excision (TME), well established in the modern curative surgery
      of rectal cancer, needs further investigation, especially with regards to the
      preservation technic of the autonomous abdominopelvic innervation currently used
      to prevent or reduce the urogenital sequelae. The Authors offer a perspective
      study over the recovery of sexual activity in a homogeneous group of 32 male
      patients submitted, because of cancer, to restorative proctectomy, with
      anatomical preparation of the hypogastric and sacral plexus. The criteria for
      eligibility were the followings: male under 70 years of age, excision of the
      primary rectal cancer with coloanal or colo-rectal anastomosis performed at less
      than 5 cm from the anal verge, staging not more than T3N2M0, without previous RT
      or other pelvic operations and without protective enterostomy, nor local or
      systemic recurrences during the follow up period. The functional results obtained
      on the basis of a questionnaire, filled in quarterly by the patients as well as
      their partners for at least a year, three months after the operation were: lack
      of sexual disorders in 37.5%, reduction of the sexual activity (partial erection,
      lack of ejaculation, anorgasmy) in the 34.4%, and no sexual activity in 28.1% of
      the patients. After 6 months the total lack of sexual activity was observed in
      only 15.6% of the patients, whereas after a year 65.6% of the patients showed a
      normal level of sexual activity. The Authors explain the preparatory technic to
      approach the mesorectum sparing the autonomous nerves and discuss the two
      fundamental surgical-anatomical aspects of the nerve-sparing technic still not
      sufficiently clarified as far as the behaviour of the pelvic visceral fascia and
      the course of the medial-rectal artery are concerned. The results obtained even
      considering the limitation in the evaluation and standardization of the genito
      sexual disorders, show the need to extend and deepen the study relative to the
      nerve-sparing technics in rectal cancer surgery.

PMID- 9004834
TI  - [Burkitt lymphoma].
AB  - The Authors report a case of Burkitt's lymphoma of the stomach in a patient
      treated ten years before for Hodgkin's lymphoma. Gastrectomy associated to
      chemotherapy is more effective than surgical treatment alone and avoids the risk
      of gastric perforation during medical treatment.

PMID- 9004835
TI  - [Non-resectable neoplasms of the biliary duct: palliative surgery vs non-surgical
      management].
AB  - A retrospective analysis comparing the results of biliary enteric anastomoses and
      non-operative management in unresectable bile duct carcinomas was carried out.
      Twenty-four patients underwent surgical drainage (Group A), and 29 were managed
      with transhepatic or endoscopic stent (Group B). Concomitant medical diseases
      were more frequent in group B patients (16.6% vs 48.2%, p < 0.03). Group A and
      group B were comparable in morbidity (29.1% vs 41.3%), mortality (12.5% vs 13.7%)
      and 1-year survival rate (21% vs 17%). Median survival was 4.2 months in group A
      and 2.6 in group B. Jaundice relief was achieved in 70.8% of group A patients and
      in 68.9% of group B. Group B patients experienced more cholangitis (p = 0.001)
      and required more hospital readmission (p = 0.0015). Quality of life was better
      in group A patients, however difference did not reach statistical significance.
      Therefore, low risk patients with unresectable hilar bile duct tumor and yet good
      life expectancy may benefit from surgical palliation.

PMID- 9004836
TI  - [Giant pedunculated leiomyoma of the fundus uteri].
AB  - The Authors report an uncommon giant leiomyoma of the uterus observed in a young
      woman after a prolonged and misknown course. The peculiar features of these large
      neoplasms as well as the diagnostic methods and the difficulties of the surgical
      treatment are discussed. The patient underwent successful surgical removal of the
      tumour with preservation of uterus and ovaries, and is still in good health after
      a two year follow up.

PMID- 9004837
TI  - [Atypical tracheal intubation].

PMID- 9004838
TI  - [The role of surgery in the treatment of primary carcinoma of the gallbladder.
      Review of 86 cases].
AB  - The records of 86 patients with primary adenocarcinoma of the gallbladder were
      reviewed. All patients were staged according to the Nevin classification. Twenty
      nine patients underwent resection, 57 were submitted to palliative procedures or
      exploratory laparotomy. Survival was directly related to tumor staging and
      modality of treatment. The 5- and 10-year survival expectancy after curative
      resection was 46.8% in stage II patients, 14.2% and 0%, respectively, in stage V
      patients. None of the unresectable cases survived beyond 24 months, except for
      one patients who lived 62 months. No significant difference in survival
      expectancy was found between resectable and unresectable patients with stage V
      tumor.

PMID- 9004839
TI  - [Treatment of the residual pancreatic stump after pancreatoduodenectomy:
      pancreatogastrostomy].
AB  - In the last few years more and more often the use of pancreaticogastrostomy (PG)
      for reconstruction after pancreatoduodenectomy (PD) has been reported. Aim of
      this paper is to review pertinent Literature and to try to define, on the basis
      of Authors' experience, the role this technique may have in reducing morbidity
      and mortality of PD. From January 1993 to June 1995 nine pancreaticogastrostomies
      were performed. Five patients had an adenocarcinoma of the papilla, two had a
      carcinoma of the distal choledochus and two had a carcinoma of the head of the
      pancreas. Major complications in this series were one operative death unrelated
      to PG and a massive bleeding from the gastric site of the anastomosis occurred 3
      days after the operation, associated to a partial dehiscence of the anastomosis,
      treated surgically. Reported results after pancreaticogastrostomy seem to
      demonstrate a dramatic decrease in morbidity and mortality after PD, however, the
      real value of this technique will be established only after a greater clinical
      experience and, when possible, wider randomized prospective studies.

PMID- 9004840
TI  - [Carotid endarterectomy: what postoperative care is needed?].
AB  - With the introduction of the diagnosis-related groups system (DRGs), hospital
      cost containment without compromising quality of care is recommended. Carotid
      endarterectomy is an effective stroke prevention treatment; the need for routine
      postoperative intensive care unit (ICU) admission is questionable and is herein
      evaluated. Between January 1994 and November 1995, 68 patients underwent 79
      carotid endarterectomies (CEAs), under general anesthesia, and were
      postoperatively monitored in a post-anesthesia care unit. 13 patients presented
      postoperative hypertension and 3 arrhythmia, while 5 patients (7.3%) experienced
      postoperative complications. Only 8 patients (11.7%) were admitted in ICU for
      treatment of persistent hypertension (3 cases) with continuous vasoactive drug
      infusion or because of postoperative complications. One patient (1.4%) died of
      post-CEA hyperperfusion syndrome. The use of a step down unit for monitoring
      patients undergoing CEAs is safe and cost-effective and also may identify
      patients requiring ICU admission.

PMID- 9004842
TI  - [Fibrous tumors localized in the pleura].
AB  - Localized fibrous tumour of the pleura is an uncommon condition which in few
      cases may exhibit malignant behaviour. Herein the Authors report a large review
      on this intrathoracic neoplasm focusing, in particular, on differential diagnosis
      between benign and malignant variants.

PMID- 9004841
TI  - [Total parenteral nutrition in digestive tract surgery: authors' experience].

PMID- 9004844
TI  - [Epidemiology of esophageal cancer].
AB  - The Authors examine the epidemiological features of esophageal cancer. This tumor
      is today the fourth neoplasm of the digestive tract, and represents 2-5% of all
      tumors.

PMID- 9004843
TI  - [A modified Thal cardioplasty in the management of advanced esophageal
      achalasia].
AB  - A modified esophagocardioplasty with gastric patch in the treatment of advanced
      achalasia is presented. The technique was employed in 4 patients from 1977
      through 1993 and satisfactory results were obtained in follow up studies up to 16
      years. This procedure provides better passage through the esophagogastric
      junction with preservation of the antireflux mechanism.

PMID- 9004846
TI  - Proceedings of the 2nd Novo Nordisk workshop on chronic renal insufficiency.
      Rome, Italy, October 26-28, 1995.

PMID- 9004847
TI  - Assault at work.

PMID- 9004845
TI  - [Current indications for video-laparoscopic surgery of adrenal gland neoplasms].
AB  - Recent advances in pathophysiology of the adrenal glands suggest new indications
      for adrenalectomy. In open surgery large incisions are needed to remove a small
      gland; on the contrary, laparoscopic procedures offer new possibilities. The
      present study is a review of the literature on indications, contraindications and
      surgical technique of laparoscopic adrenalectomy. Evaluations of these initial
      experiences are favourable, however, due to the small number of patients operated
      and to the short follow up, a definitive opinion on the role of laparoscopic
      surgery for adrenalectomy has to be formulated.

PMID- 9004849
TI  - Selected papers from the 16th annual conference on peritoneal dialysis. Seattle,
      Washington, February 21-23, 1996.

PMID- 9004848
TI  - Your caring sharing manager?

PMID- 9004850
TI  - [High incidence of anencephaly in the East coast of the Maracaibo Lake: a myth].

PMID- 9004852
TI  - [Liver function in patients exposed to a toluene in a hydrocarbon processing
      plant].
AB  - Since the hepatotoxic role of toluene in exposed workers from the petroleum and
      petrochemical industries chronically exposed to low concentration has no been
      entirely dilucidated, this transversal study was undertaken in order to clarify
      the situation in the local industries. A group of 33 non-exposed men workers of
      such industries (group control, aged 33.0 +/- 4.88 years) were compared with 33
      toluene-exposed men (aged 35.0 +/- 9.33 years) from the related industries, with
      a minimal of 6 months exposition time to toluene and without liver disease
      history. In addition to a complete occupational diseases medical history, each
      subject was tested by both a venous blood sample (to determine prothrombin, total
      and fractioned bilirubin, total and fractioned proteins, liver enzymes and
      cholesterol) and urine sample (hippuric acid). Also the environmental
      concentration of toluene in working areas was determined by gas chromatography,
      which was below the recommended standard levels in working areas. Although the
      analyzed parameters were in the normal range, it was observed that those workers
      with known alcohol ingestion and toluene exposition had several abnormalities.
      The results of this study confirm that toluene may have a synergistic hepatotoxic
      effect in toluene-exposed workers that are alcohol consumers. The alcohol in
      considered as a confounding factor and it is not possible to rule out in the
      etiology of hepatic changes detected in the study.

PMID- 9004853
TI  - [Preventive program of birth defects: incidence of anencephaly in Maracaibo,
      Venezuela. 1993-1996 period].
AB  - Incidence of anencephaly in the State of Zulia, and specifically in the Eastern
      Coast of Lake Maracaibo, an oil exploitation area, has been declared high since
      the beginning of the 80's, coincident with the generalized use of ultrasound as a
      diagnostic tool for fetal evaluation. Through the Birth Defects Preventive
      Program, established at the Hospital Chiquinquira in Maracaibo, we have developed
      a fourfold strategy for the study of birth defects: i) analysis of more than
      32,332 ultrasound evaluations within the Ultrasound Service, between 1993 and
      1996, ii) a case-control malformation registry beginning in 1995, iii) a study of
      malformed stillbirths at the Pathology Service, observed after 4232 deliveries
      within this hospital, and iv) a registry of over 638 mothers with high risk
      pregnancy for fetal defects detected at the prenatal clinic and carried out at
      the Perinatal Medical Genetics Service. As a reference population we study 345
      medical histories obtained from the Medical Genetics and Prenatal Diagnostic
      Service at Hospital Coromoto, and oil companies related medical facility. This
      approach has led us to conclude that the incidence of anencephaly in the State of
      Zulia is 0.75/1000, significantly similar to that expected for most populations.

PMID- 9004854
TI  - [Topography of ribosomal proteins: reconsideration of of protein map of small
      ribosomal subunit].
AB  - Exposure of proteins on the surface of the small (30S) ribosomal subunit of
      Escherichia coli was studied by the hot tritium bombardment technique. Eight of
      21 proteins of the 30 S subunit (S3, S8, S10, S12, S15, S16, S17, and S19) had
      virtually no groups exposed on the surface of the particle, i.e., they were
      mainly hidden inside. Seven proteins (S1, S4, S5, S7, S18, S20, and S21) were all
      well exposed on the surface of the particle, thus being outside proteins. The
      remaining proteins (S2, S6, S9 and/or S11, S13, and S14) were partially exposed.
      On the basis of these results a reconcilement of the three-dimensional protein
      map of the small ribosomal subunit has been done and corrected model is proposed.

PMID- 9004851
TI  - [Family education, a model for allergy prevention].
AB  - It is frequent the lack of family adherence toward the therapeutic measures of
      the allergic diseases. The incidence in the therapeutic non compliance of the
      asthmatic patients vary from 20 to 80%. In the last decades, the symptomatic
      expression of the atopic diseases (AD) in the infancy, and in the adolescence of
      Venezuelans has been transformed into a health care problem, with an inaccessible
      therapeutic cost for the state and the family. The setup of the first allergic
      prevention program improved attitudes and perceptions toward bronchial asthma,
      allergic rhinitis, and atopic dermatitis, by the education of the risk family
      group, based on the results from previous investigations and adapted to the
      procedures and customs that govern our current society. A research project,
      through a multi-disciplinary group included an educational program model for the
      prevention of allergic diseases in a population from Caracas, Venezuelan allergic
      pregnant mothers, and their respective couples of a high and middle socioeconomic
      levels with no helminthic infections (n = 482), group A. Two subgroups were
      randomly selected for prospective evaluation: A1 (n = 20) without participation
      in the preventive program or control group, and A2 (n = 15) with participation in
      the program or intervened group, including strategies to be applied by the
      family, application of measures and reached goals; immunologic, pediatric, and
      nutritional sequential control; group B (n = 66), to validate the laboratory
      tests, and group C (n = 364) to validate immunoclinical diagnoses, in vivo
      immunodiagnostic tests to the parents and children (clinical history, skin prick
      tests for cow's milk, egg white, wheat, soybean, cladosporium and
      Dermatophagoides pteronnysinus), and in vitro tests (total serum IgE, Phadiatop,
      and Rast to the allergens previously selected). In conclusion, the program
      permits the identification of atopic risk children, sponsors the systematical
      application of intervention measures, economic, viable and projected toward the
      family affected, indicating a positive change through a self-family-management
      training and new conduct plans, facilitating the participation among the family,
      the community and the health team, that certifies, an optimistic therapy in the
      reduction of the clinical manifestations of the atopic diseases in young infants
      from this tropical population studied.

PMID- 9004855
TI  - [Crystal structure of fully oxidized cytochrome c-oxidase from the bovine heart
      at 2.8 A resolution].
AB  - Structural and functional studies on cytochrome c oxidase before the crystal
      structures appeared, are summarized to show the importance of X-ray crystal
      structure at the atomic resolution for understanding mechanism of the enzyme
      reaction, O2 reduction coupled with proton pumping. Crystal structure of bovine
      heart enzyme at the fully oxidized state at 2.8 A resolution are reviewed to
      evaluate of the contribution for understanding the enzyme reaction mechanism.
      Effects of detergent structure on the crystallization conditions of the bovine
      heart cytochrome c oxidase, which was critical for obtaining the X-ray crystal
      structure, are presented to propose a possible mechanism of crystallization of
      multicomponent membrane proteins.

PMID- 9004856
TI  - [Organization of biochemical systems].
AB  - Own and literature data on molecular organization of biological system from a
      single enzymatic complex to a large association of metabolon type are reviewed
      with emphasis on characterization of forces involved in the process of
      aggregation of protein molecules and a role of shaperons in organization of some
      complexes. Possible mechanism of chaperon transport along cytoskeleton structures
      is suggested. Problems of a theory of metabolon organization of enzymes and a
      role of an anchor in coordination of action of multienzyme complexes are
      discussed.

PMID- 9004857
TI  - [Molecular mechanism of morphogenesis: a theory of locational DNA].
AB  - A molecular mechanism of reading of positional information by cells in
      morphogenesis and regeneration is proposed. It permits to translate the genome
      information into three-dimensional form of an organism. In the mechanism, a new
      fraction of DNA, so called "location DNA" is used which is suggested as a
      substitution instead of a former "egoistic" DNA. Domains, that are formed by this
      DNA and packed by lipid-containing bridges, are selectively unpacking in the
      gradient of inductor, the concentration of which positively correlates with the
      production of free radicals in the cells. Free radicals induce a selective
      destruction of lipid bridges which are variable in their resistance to the
      oxidative destruction. Hence the domains of location DNA are selectively
      decomactizing and activiting after bridge's elimination. In this way, a reading
      of positional information is performed. An epigenetic memory concerning the
      cellular determination state, that was already achieved, is based on the so
      called process of triplexation, the essence of which is a triplex formation,
      between signal RNA molecule and nascent double stranded DNA. A triplex is formed
      during the lagging strand synthesis or in the course of DNA repair synthesis. A
      telomeric element of postmitotic neurons, so called chronomere, assists to the
      organism in measuring of the flow of biological time, while chronomere length is
      an indicator of biological age of the organism.

PMID- 9004858
TI  - [Phosphate sites of RNA-ligands interacting with ribosome at different stages of
      translation. Thiophosphate method of analysis].
AB  - A novel footprinting method was recently developed which identifies phosphate
      groups of RNA involved in strong RNA-RNA and RNA-protein interactions. The method
      is based on iodine-dependent RNA cleavage at phosphothioate groups as long as
      these groups are not protected from iodine. Our recent studies of mRNA and tRNA
      regions protected in active ribosomes are summarized; initiation state of
      ribosomes as well as two elongation states in pre- and post-translocational
      states were analyzed. Only one phosphate group of mRNA, which was two positions
      upstream of the decoding codons, was weakly protected in longation complexes,
      whereas this group and the phosphate groups in the Shine-Dalgarno sequence were
      protected in the initiation complex. No protection was observed downstream of the
      decoding codons. On the contrary, numerous phosphate residues of tRNA were
      protected by the ribosome. The tRNA protection patterns significantly varied
      between two tRNAs simultaneously bound to the ribosome. The protection pattern of
      an individual tRNA was not significantly affected by translocation. The data
      indicate that both tRNA molecules are tightly bound to the ribosome, whereas mRNA
      is fixed predominantly by two tRNAs via codon-anticodon interaction. A possible
      translocation mechanism is suggested.

PMID- 9004860
TI  - [Biological role and mechanisms of realization of the Crabtree effect in rapidly
      proliferating cells. The role of Ca2+ ions].
AB  - Characteristic differences in energy supply systems in normal differentiated
      cells versus rapidly proliferating cells including tumor cells are summarized.
      Previously suggested mechanisms of the Crabtree effect (inhibition of respiration
      by glycolysis metabolites) are specifically evaluated. The effect cannot be
      explained by the competition of glycolysis systems with oxidative phosphorylation
      for ADP and Pi. A novel mechanism of the Crabtree effect is suggested based on
      regulatory (inhibitory) effect of Ca2+ as the second messenger on oxidative
      phosphorylation in tumor cells and other rapidly proliferating cells. The
      Crabtree effect can be one of the main mechanisms which switch cellular energy
      metabolism form oxidation to anaerobic glycolysis, the latter being more
      beneficial for reductive biosynthetic reactions and rapid growth of the cells.

PMID- 9004859
TI  - [Automation on membranes: countercurrent isotachophoresis and
      immunoelectrochromatography].
AB  - The review discusses two related methods--counterflow isotachophoresis and
      immunoaffinity electrochromatography on porous membranes developed by the
      authors. The methods exploit the peculiarity of electroendosmosis in porous
      membranes at the conditions of discontinues electrophoresis. There are described
      the principles and application of the above methods for automatic performance of
      electrophoretic analysis of low-protein biological fluids, of western blotting,
      epitope analysis of monoclonal antibodies and multiantigen assays. The
      possibility of DNA-binding protein detection is also considered.

PMID- 9004861
TI  - [Structure, regulation, and denaturation of muscle glycogen phosphorylase b].
AB  - The review summarizes data on structure, allosteric regulation, and denaturation
      of muscle glycogen phosphorylase b. Specific attention is paid to correlations
      between the structure and function of phosphorylase b and molecular mechanism of
      its allosteric regulation. Chemical and thermal denaturation of phosphorylase b
      is reviewed.

PMID- 9004862
TI  - [The other side of metabolism].
AB  - Since the discovery of enzymic fermentation by Louis Paster, the idea had been
      widely spread in biochemistry that all molecular interconversions and
      interactions in living systems are provided by the enzymes. However, recent
      advances in sensitivity and accuracy of analytical methods lead to isolation and
      identification of a variety of products that cannot be mapped to a specific
      biochemical pathway. These products appear in the organism because the chemical
      characteristics of biomolecules are not limited to the needs of living systems
      realized through enzyme-catalyzed processes. This review for the first time
      attempts to summarize such nonenzymic interactions: (i) products of biogenic
      amine adduct formation to carbonyl-containing compounds in Pictet-Spengler
      reaction (endogenous neurotoxins which alter mitochondrial functions thus
      evidently participating in development of age-related cerebral aberrations, i.e.,
      parkinsonism); (ii) products of Schiff base formation with subsequent Amadori
      rearrangement (nonenzymic glycation of proteins involved in age-related diabetic
      disorders and atherosclerosis); (iii) products of Michael addition of
      methylglyoxal, 4-hydroxynonenal, and other products of nonenzymic conversions of
      carbohydrates and lipids; (iv) products of biomolecule modification with nitrogen
      and oxygen-derived free radicals which contribute to cancer and aging. Some
      applications of these problems in evolutionary and medical biology are reviewed.

PMID- 9004863
TI  - [RNA-binding properties of ribosomal protein L1 from Thermus thermophilus].
AB  - Fragments of the ribosomal protein L1 from Thermus thermophilus were obtained by
      limited trypsinolysis and spontaneous proteolysis. Binding of the intact L1 and
      its proteolytic fragments to 23S ribosomal RNA was studied. First eight N
      terminal amino acids are important for RNA binding because protein L1 lacking
      these amino acids exhibits reduced 23S rRNA binding. Additional cleavage of the
      polypeptide chain between residues 36 and 37 completely abolishes RNA binding.
      Comparison of these data with recently determined structure of protein L1 from T.
      thermophilus suggests the nature of interactions which can determine specific and
      strong association of the protein L1 with 23S rRNA.

PMID- 9004864
TI  - [Biochemistry of space and time (telomeres, telomerases, and longevity of cell
      populations and multicellular organisms].
AB  - Analysis of recent data on telomeres and telomerases, limitations of
      proliferative potential of untransformed cells (Hayflick's limit), kinetics and
      molecular mechanism of cell proliferation and differentiation, and factors that
      determine the longevity of multicellular organisms suggests that: (i) chromosome
      end shortening during consecutive divisions of cells that lack telomerase limits
      cell proliferation beyond Hayflick's limit; (ii) Hayflick's limit can be a
      manifestation of mechanisms that determine the size of the living organism (it
      correlates with longevity) but not the longevity of multicellular organisms.

PMID- 9004865
TI  - [In its intermembrane space the mitochondrion hides the "suicide protein", which
      being released into cytosol causes apoptosis].

PMID- 9004866
TI  - [Spatial distribution of facial volumes. Ontogenetic and phylogenetic study with
      vestibular orientation].
AB  - On cephalic skeleton of Man and two species of chimpanzees, statistically
      considered during their growing, a sagittal area is measured in facial mass and
      total face. Barycenters are determined. This points describe, in vestibular axis,
      ontogenic curves with posterior concavity more important in Man. Remarkable
      relations exist between barycenters and several facial and mandibular points, and
      with those of frontal and parietal vault.

PMID- 9004867
TI  - [Teratology "from Geoffroy Saint-Hilaire to the present"].
AB  - Teratology, science of monsters, exists during the periods of Antiquity, Middle
      Ages, Renaissance, ... but its comes more precise at the XIXth century with
      Etienne. Geoffroy Saint Hilaire who studies several anomalies; he was interested
      in celosomia, cyclocephalia, anencephaly, twin monsters ... His son, Isidore
      Geoffroy Saint Hilaire, creates the word "Teratologie" and specifies the
      teratologic classification; he studies omphalosites, celosomia, hermaphrodite,
      twin monsters. During the XIXth century, the development of experimental
      embriology and teratogenesis is very important. During le XXth century the
      studies of morphologic teratology are specified. Famous living monsters are
      described; experimental teratogenese is improved; the mecanism and the etiology
      are more known. It is also the beguining of the teratologic surgery and of the
      antenatal diagnostic.

PMID- 9004868
TI  - [Preliminary analysis of the modifications of spinal curves, in extreme
      amplitudes, observed in rhythmic and athletic gymnastics].
AB  - Trained users of Rhythmic and Athletic Gymnastic, present kinetic spinal vast
      extents. Analysis, with pasted cutaneous markers, shows that, according to the
      codified movement, various segments of the vertebral column are requested and
      realized important displacements. Nevertheless, to have an homogeneous attitude,
      some subjects request more either lumbar or thoracic segments, of both. To
      prevent frequent spinal pain, it is important to realize a preliminary subject
      selection using their total spine and to improve protection by adapted gymnastic.

PMID- 9004869
TI  - [Comparative study of static curves of the human spine in vivo during exercise
      and stretching in men and women].
AB  - Comparative study of static curves of the thoracic and lumbar spine in men and
      women has been realized under constraints of compression by weightlifting and
      elongation by exercise to parallel bars. In two athletic practices, curves
      decrease their arrow, ending to a straighter and more rigid column. This behavior
      expresses muscular actions. The greatest amplitude of displacement, observed in
      female series, shows lesser muscular forces in connection with a poor practice of
      exercises of body building.

PMID- 9004870
TI  - [Measurement of the torsion of the two bones of the forearm: evaluation of
      tomodensitometric reference points].
AB  - In order to evaluate the rotation following radial and ulnar fractures, the
      authors propose radial, ulnar and humeral landmarks for a CT scan measure of
      radial and ulnar torsion. In the ulna, the dorsal at the level of the proximal
      radio-ulnar articulation, as well as the bicondylar axis of the humerus seem to
      be fair landmarks. Distally, the styloid process is regularly identified and may
      serve as distal reference for the measure. In the radius, the ventral face of the
      distal epiphysis is always clearly visualized and seems to be a good landmark;
      the radial tuberosity, which was primarily chosen as proximal reference, is not
      consistently identified and cannot be used as landmark. The variation of position
      of the radial head with respect to the capitulum during pronation needs too know
      the amount of this movement before the measure if the bicondylar humeral axis is
      chosen as proximal reference.

PMID- 9004871
TI  - [Determination of the cutaneous sagittal profile of the face from knowledge of
      the bony profile in the European young adult].
AB  - We use a pattern of 51 living subjects of which sex is known, 21 years aged, and
      of which we have teleradiographic tracing (with setting off cutaneous outline).
      Vestibular orientation is made and statistical average-type is established by
      vestibular coordinates showing position of 6 skeletal points and 7 cutaneous
      ones. Their spatial variability is studied. Cutaneous elements are situated
      relatively to their bony homologous, by regression equations, single and
      multiple, on each of the two coordinates. This study conclude is: in spite of the
      use of complex statistical methodologies, uncertainties persists as for validity
      of face reconstruction for a given subject.

PMID- 9004872
TI  - [Principles of effectiveness control in therapy of glaucoma].
AB  - There are two levels at which the efficacy of glaucoma therapy can be determined:
      first, the therapeutic trial and second, the experience gained when treating
      individual patients in the daily practice. At each level, various difficulties
      arise. At either level, however, the main problem is that there is no way to
      check on patient compliance. A trial on the efficacy of glaucoma therapy needs to
      be thoroughly planned and performed, correct statistical methods must be used,
      and the therapy must be critically evaluated a review of studies on glaucoma
      therapy for the years 1988 and 1993 showed the difficulties in planning and
      enforcing a correct study design. Most studies suffer from lack of adaptation to
      the characteristic features of primary open-angle glaucoma, the most important of
      all being its chronic course with minimal changes over many years once pressure
      is regulated. Thus, long-term studies are mandatory with simultaneous assessment
      of intraocular pressure (IOP), the visual field and the morphology of the optic
      nerve head (ONH). Measurement of the IOP is the parameter that can be most
      reliably checked on. Increased IOP represents the main cause for glaucoma damage
      not the damage itself. For the early detection of glaucoma, morphometry of the
      ONH is the most reliable method, but it is still quite rough. The use of
      perimetry for early detection and follow-up of glaucoma is overestimated. Given
      the above-mentioned characteristic features of the disease, sufficient damage
      with corresponding perimetric and morphometric changes does not occur in the
      short time periods chosen for therapeutic trials. The future will show whether
      the blood supply of the ONH will be of primary interest in glaucoma detection and
      control of treatment efficacy. New and promising methods for measurement of the
      blood supply of the ONH are emerging. Last but not least, control of efficacy in
      glaucoma treatment should include cost-effect analyses. Such studies are almost
      nonexistent at present.

PMID- 9004874
TI  - [Can the extent of glaucoma damage be quantified with laser polarimetry by in
      vivo measurement of retinal nerve fiber density? A clinical study].
AB  - Thirty-eight eyes of 38 glaucoma patients with a defined up-down asymmetry of
      visual field loss (VFL) were examined to ascertain whether there was
      corresponding up-down asymmetry of nerve fiber layer thickness (NFLT), calculated
      by laser polarimetry (LP). The correspondence was found to be closer for small up
      down asymmetry of VFL then for medium or large up-down asymmetry. An
      approximately 6% greater NFLT in the lower than in the upper retinal half was
      revealed found by examination of 62 eyes of 62 normals. Considering this NFLT
      asymmetry in normals, there was a non-significant tendency towards correspondence
      between the up-down asymmetry of VFL and the up-down asymmetry of NFLT for the
      group of glaucoma patients with large up-down asymmetry of VFL. However, in about
      40% of cases there was no such correspondence, so that staging of the
      glaucomatous disease has to be done by perimetry and is not possible by LP
      (software version 06/93).

PMID- 9004873
TI  - [Value of scanning laser ophthalmoscopy and polarimetry compared with perimetry
      in evaluating glaucomatous changes in the optic papilla and nerve fiber layer].
AB  - The aim of the study was to establish quantitative correlations between
      morphological changes at the optic nerve head (ONH) and the retinal nerve fiber
      layer (NFL) and functional abnormalities i.e. visual field alterations in
      glaucoma. A cross-sectional study of open-angle glaucoma patients of various
      stages was performed. Scanning laser tomographic (TopSS) assessment of the ONH
      and scanning laser polarimetric (Nerve Fiber Analyzer) measurements of the
      peripapillary NFL thickness (NFLT) were compared to results of computerized
      static perimetry (Octopus G-1). One eye from each of 157 glaucoma suspects (n =
      58) and patients with established open-angle glaucoma (n = 99) was assessed. The
      parameter "modulation" (difference between maximum and minimum of NFLT) gave the
      best correlation (r2 = 0.23) to the visual field index for mean sensitivity.
      Tomography gave the best correlation between the neuroretinal rim area at the
      inferior and superior pole of the ONH and the visual field index loss variance
      (r2 = 0.20). Conventional planimetric data of the ONH and clinical assessment of
      the NFL yielded slightly better correlations to the visual field data than the
      scanning laser tomography or polarimetry. Although NFL parameters are more
      complicated to obtain, they yield better correlations to diffuse visual field
      loss than parameters of the ONH. The new scanning laser techniques do not improve
      these correlations between morphology and function; however, they allow objective
      assessment of ONH and NFL parameters without mydriasis.

PMID- 9004875
TI  - [Topometry of the optic papilla with the glaucoma-scope].
AB  - Reproducibility of measurements of the "Glaucoma-Scope", a new topometric device
      (software version 3.12), was assessed by optic disk analysis of 10 eyes in 10
      healthy subjects. Each analysis was carried out by 4 independent observers.
      Examinations of one of these eyes were repeated 10 times by each one of the 4
      observers. The instrument was also applied to a sample of 117 eyes in 60 patients
      from a glaucoma clinic. The minimal requirements were determined to be a pupil
      diameter of 5 mm and lens-related visual acuity > 0.8. The coefficient of
      variation for the different optic disk parameters in the repeated examinations
      ranged from 3.5% to 15.7%. The maximal discrepancy between values of vertical C/D
      ratio within any of the subjects ranged from 0.01 to 0.12 (mean 0.05). Glaucoma
      Scope measurements revealed a smaller value for disk area than those from
      computer-assisted manual planimetry, with a constant factor of 0.81. The
      measurement of vertical C/D ratio by Glaucoma-Scope and a stereoscopic estimate
      correlated highly in a subset consisting of 20 glaucoma patients and the 10
      healthy subjects (r = 0.786; p < 0.0001). A considerable discrepancy (larger or
      smaller) was apparent between values found through clinical inspection of 6 of
      the 117 eyes (4 of 60 patients) and those found with the Glaucoma-Scope. In these
      6 eyes subsequent analyses utilizing a more recent software version yielded a
      good correlation between the two methods. The Glaucoma-Scope allows sufficiently
      reproducible optic disk topometry.

PMID- 9004876
TI  - [Chronic open angle glaucoma: correlation of pattern electroretinography and
      visual field indices].
AB  - The pattern electroretinogram has already proven to be useful in detecting early
      stages of chronic open-angle glaucoma. We were interested in the degree of
      correlation between pattern ERG amplitudes and definite visual field defects.
      Fifteen glaucoma patients with a wide range of visual field defects were examined
      with pattern electroretinogram (stimulus with reversal rate of 8/s, checksizes of
      0.9 degree and 6.9 degrees, covering a visual field of up to 9 degrees
      eccentricity). The patients' visual fields obtained with the Octopus 1-2-3
      perimeter were analyzed with the perimetric analysis system PERIDATA using the
      indices of conformity for localized defects and the regional indices created from
      the mean deviation in certain parts of the 30 degrees field. In our results we
      were only able to find a significant correlation within the 5% level between the
      pattern ERG amplitudes and the sector index (large checksize, correlation
      coefficient r = -0.58, p = 0.03) and with the mean deviation in the region
      between 10 degrees and 20 degrees (small checksize, r = -0.538, p = 0.044). In
      summary, a marginal correlation between electrophysiological data and perimetric
      parameters was demonstrated. We try to explain the remarkable correlation between
      the amplitudes (small pattern) that were recorded from the central 9 degrees with
      the mean defects from the visual field peripheral of 10 degrees with the frequent
      combination of diffuse and localized field defects in glaucoma. Examination with
      the pattern ERG alone does not seem to be appropriate for grading the focal
      glaucomatous damage.

PMID- 9004877
TI  - [Clinical calibration and in vitro evaluation of the validity of 2 microprocessor
      controlled tonometers].
AB  - In a randomised clinical study two new microprocessor-controlled tonometers
      working according to the Mackay-Marg principle (Tono-Pen and ProTon, two samples
      of each) and two established applanation tonometers [hand-held applanation
      tonometer, Draeger (HAT) and Goldmann tonometer] were compared with respect to
      accuracy, precision, examiner dependence and internal measurement differences
      (Tono-Pen I vs II, ProTon I vs II). The four tonometers were used by two
      examiners six times on each of 193 eyes of 100 patients of the university eye
      department. The same measuring procedure was performed on four cadaver eyes in
      situ, using a manometer system. The correlation coefficient between Tono-Pen and
      HAT and between ProTon and HAT was 0.9, with a high standard deviation, about +/-
      3.1 mmHg. HAT gave the best results in repetitive measurements in the same eye
      (precision: r = 0.92, SD = +/- 1.41 mmHg). In applanation tonometers but not in
      Mackay-Marg tonometers measurement values depended significantly on the
      physician. There was a significantly higher standard deviation between Tono-Pen I
      and II than between ProTon I and II. Concerning in vitro calibration series on
      human bulbs (manometry), accuracy was high with each tonometer. The regression
      line of HAT is similar to that of ProTon. Tono-Pen overestimates the
      manometrically determined intraocular pressure. Because of their lack of
      precision the two new tonometers are not suitable for clinical use.

PMID- 9004878
TI  - [Contact glass tonometer].
AB  - This paper present a tonometer incorporated in a contact lens, which allows
      simultaneous measurement of intraocular pressure and performance ophthalmoscopy.
      The tonometer can record the pulse curve continuously, which can give us an
      indication of any circulatory problem. The device is therefore expected to yield
      additional information useful for the diagnosis of early glaucoma. Te device has
      three force sensors built in, which allow continuous measurement of the force
      exerted on the eye surface by the contact lens. The force of the contact lens on
      the eye can be altered and makes the adjustment of different eye pressures
      possible. These induced changes of the eye pressure and their influence on the
      fundus can be checked. We have taken some measurements on enucleated human eyes
      to compare our device with a Statham tansducer in the vitreous. We found a good
      correlation. We are currently taking measurements in volunteers. The clinical
      relevance of these observations and measurements will be examined in a future
      study.

PMID- 9004879
TI  - [Risk factors for development of argon laser trabeculoplasty failure producing
      membrane in the chamber angle].
AB  - INTRODUCTION: The major cause of ALT failure is membrane formation in the chamber
      angle. The aim of this retrospective study was to identify possible risk factors.
      MATERIAL AND METHODS: We studied sections from the surgical specimens from all
      trabeculectomies at our department within 2 years. We identified 122 eyes with at
      least one preoperative ALT. In 46 specimens enough trabecular meshwork for
      morphological analysis was present. RESULTS: Half of the patients showed a
      membrane covering the trabecular meshwork. In 14 of 23 eyes we could see this
      membrane even at low-power magnification (40 x). Various possible risk factors
      were evaluated, but none showed a significant correlation. When we compared only
      these eyes with membranes visible at low-power magnification with eyes without,
      however, we found a significant difference in the number of ALTs (mean +/- SD
      2.07 +/- 0.73 vs 1.48 +/- 0.59; P = 0.026) and preoperative intraocular pressure
      (32.0 +/- 9.7 mmHg vs 26.2 +/- 8.4 mmHg; P = 0.04). CONCLUSION: We found no
      distinct risk factor for membrane formation, but it becomes more frequent with
      every additional laser treatment.

PMID- 9004880
TI  - [Intraocular rt-PA injection in fibrin formation after combined glaucoma and
      cataract operation].
AB  - BACKGROUND: The fibrinolytic drug rt-PA, which has been successfully used
      systemically to treat arterial and venous occlusions, is now available for local,
      intraocular injection. rt-PA converts plasminogen to plasmin, which in turn is
      able to lyse fibrin and fibrin clots. Intraocular surgery, trauma and
      inflammation may lead to intraocular accumulation of fibrin. Treatment of this
      type of complication with high-dose corticosteroids is protracted and often
      unsuccessful. PATIENTS: Eight patients (age 59-75 years) with fibrin formation
      following phacoemulsification and IOL implantation combined with trabeculectomy
      were treated by intraocular injection of 10 micrograms rt-PA. The intraocular
      status following the local fibrinolytic therapy was documented by biomicroscopy,
      photography and laser-flare Tyndallometry on days 1, 2 and 8. RESULTS: In all
      patients the fibrin clots dissolved completely. Neither relapses nor adverse
      affects were noted. CONCLUSIONS: The intraocular application of rt-PA results in
      an efficient fibrinolytic effect, which prohibits potential complications of
      combined glaucoma and cataract surgery due to fibrin formation.

PMID- 9004881
TI  - [Single dose intraoperative administration of 5-fluorouracil (5-FU) in
      trabeculectomy. Long-term results of a pilot study].
AB  - 5-Fluorouracil (5-FU) improves the success of trabeculectomy. Since in vitro
      studies showed a prolonged effect of 36 days of growth inhibition with a single
      dose of 5-FU, 5-FU is applied intraoperatively. To evaluate the effect of
      intraoperatively applied 5-FU, we compared 13 (low-risk) patients with
      intraoperative application of 5-FU to a control group matched by age, diagnosis,
      sex and stage of glaucoma. Postoperatively on day 4 the IOP was significant lower
      (4.8 mmHg) in the 5-FU-group in comparison to the untreated group (P = 0.005;
      power 0.80). After 1 week the difference decreased to 2 mmHg and was not
      significant any more (P = 0.16). After 1 week a lower mean intraocular pressure
      of 2 mmHg was found with a P-value of 0.16. It may be that these results are not
      just due to an antiproliferative mechanism; a direct toxic effect of 5-FU should
      be considered. 5-FU side effects such as corneal complications and inflammatory
      reaction were not increased in the 5-FU group. However, one case of persistent
      hypotony was seen in the 5-FU group. This study found intraoperative use of 5-FU
      to be a safe procedure with a pronounced capacity to lower IOP in the direct
      postoperative phase. However, this effect may not be based on an
      antiproliferative effect alone, but might be of toxic origin.

PMID- 9004882
TI  - [Targetted ablation of the trabecular meshwork with excimer laser in primary open
      angle glaucoma].
AB  - The trabecular meshwork and the inner wall of Schlemm's canal constitute 75% of
      the outflow resistance of the aqueous. Attempts to improve the outflow facility
      with laser beams have not been satisfactory because they produced thermal effects
      with coagulation of the trabecular meshwork. With the excimer laser tissue can be
      removed with minimal thermal effects and necrosis. This results in minimal scar
      formation. With these qualities the excimer laser lends itself very well for
      ablation of the trabecular meshwork. It should be possible to create an open
      connection between the anterior chamber and Schlemm's canal. The goal of our
      experiments is selected ablation of the trabecular meshwork and the inner wall of
      Schlemm's canal in order to create pores and enhance the outflow facility. First
      experiments were carried out on pig and cadaver eyes, followed by eyes destined
      for enucleation because of malignant melanomas. Finally, we treated 6 patients
      with open-angle glaucoma. In 4 cases intraocular pressure was reduced by 11 mmHg
      over a follow-up time of 5 months. In 2 cases IOP rose by 2 mmHg in spite of
      medication. These preliminary results encourage us to continue with our
      investigation because there could be a possibility of an effective glaucoma
      therapy.

PMID- 9004883
TI  - [Antiproliferative therapy with 5-fluorouracil in erbium:YAG laser sclerostomy ab
      externo].
AB  - BACKGROUND: Erbium laser sclerostomy (ELS) ab externo is a minimally invasive
      addition to conventional fistulating glaucoma surgery. To date, the success rate
      of this method is lower than that of trabeculectomy or goniotrepanation. The
      chief cause of therapy failure is postoperative episcleral scarring of the bleb.
      It was the aim of the present study to decrease the occlusion rate of this
      complication. PATIENTS AND METHODS: 41 eyes were treated with subconjunctival
      injections of 5-fluorouracil perioperatively to an intended total dose of 40 mg
      to prevent episcleral scarring. At the same time, bigger probe diameters were
      used (550 microns and 700 microns instead of 300 microns). RESULTS: After 3
      months, the proportion of patients with regulated intraocular pressure after
      using bigger probe diameters combined with anti-proliferative therapy was
      significantly higher (550 microns fiber +5-FU: 73%; 700 microns fiber +5-FU: 71%)
      than for a 300 microns fiber without 5-FU (38%). Average intraocular pressure in
      successful cases was 11.6 +/- 4.2 mmHg in the 550 microns fiber +5-FU group and
      12.3 +/- 4.0 mmHg in the 700 microns fiber +5-FU group. CONCLUSION: The short
      term results of erbium laser sclerostomy as a minimally invasive technique can be
      improved by using increasing laser fiber diameters and by perioperative
      injections of 5-FU to prevent episcleral fibrosis.

PMID- 9004884
TI  - [Cyclophotocoagulation with the diode laser in contact procedure with a new
      focussing tip].
AB  - During contact cyclophotocoagulation (CPC) energy is transmitted through the
      conjunctiva and the sclera by direct contact of a plain fibre tip. Alteration and
      scarring of the conjunctiva and the outer parts of the sclera cannot always be
      avoided. We used a new fibre tip which defocuses the laser light on the
      conjunctiva and sclera and focuses the laser light on the ciliar body. The
      coupling and focusing medium between fibre and sclera is a small glass ball (3 mm
      diameter). METHODS: Up to now we have treated 52 human eyes of 35 patients
      affected by refractory glaucoma using a diode laser (Zeiss Visulas II) coupled
      with a 200-microns fibre and a 3-mm focusing ball tip. In all cases 20-40 spots
      were applied 1.5 mm posterior of the limbus, power varied between 1.5 and 2.2 W
      and exposure time was 1.5 s. RESULTS: In all cases the conjunctiva and the sclera
      was unaltered. The mean follow-up time was 224 days. The mean IOP values +/- SD
      before treatment and 6 days, 4 weeks and 1 year after treatment were 40.9 +/-
      7.1, 19.3 +/- 7.9, 22.4 +/- 14.8 and 17.2 +/- 11.3 mmHg. No positive, linear
      correlation was found between number of spots and IOP drop after 6 days. There
      was considerable individual variance. The main complications were anterior
      fibrinous uveitis (10%), slight vitreous haemorrhage (2/52) and transitory
      hypotony (2/52). In one enucleated eye structural alterations to the pigmented
      and non-pigmented epithelial cells of the ciliary body were found histologically.
      CONCLUSIONS: Contact diode CPC can significantly reduce IOP, and the conjunctiva
      and sclera can be left totally unaltered by the focusing ball tip used in this
      study.

PMID- 9004886
TI  - [Changes in extracellular matrix in the lamina cribosa of patients with secondary
      glaucoma].
AB  - The aim of this study was to analyze the localization and distribution of
      extracellular matrix in normal and glaucomatous damaged optic discs using
      immunohistochemical methods. Five eyes donated for corneal allografting without
      any history of glaucoma and three other eyes with secondary glaucoma were
      studied. Immunohistochemical reactions were performed with antibodies against
      collagen types I, III, IV and VI and against laminin, proliferating antigen KI67
      and GFAP. In glaucomatous eyes the characteristic arrangement of collagen fibrils
      is lacking. Septa of the lamina cribrosa appear enlarged. The immunoreactivity of
      all examined collagen types is stronger in glaucomatous eyes. The axon basement
      membranes show an irregular and interrupted pattern. The number of proliferating
      cells with positive GFAP staining in glaucomatous cribriform plates is distinctly
      higher. We postulate that fibroblasts and astrocytes in the stroma of
      glaucomatous lamina cribrosa could be stimulated to increased and uncontrolled
      proliferation. Associated disorganization and raised secretion of extracellular
      matrix may lead to axon constriction and, secondarily, to neural degeneration.

PMID- 9004887
TI  - [How can the success of a glaucoma operation be predicted?].
AB  - PURPOSE: The effect of glaucoma surgery can simply be measured in terms of
      intraocular pressure (IOP) reduction. However, IOP reduction is not the final
      goal of glaucoma surgery, but rather long-term visual field preservation. Visual
      field preservation, on the other hand, can only be judged many years after
      surgery. Therefore, a formula that could be used to define the success of a
      pressure-lowering operation soon after surgery should take account of IOP
      reduction, but the correlation between "successful IOP reduction" and "long-term
      visual field preservation" should be as high as possible. METHODS: In an attempt
      to find such a formula, we examined the long-term course with reference to both
      IOP and visual field in 108 patients (mean follow-up 7.9 years). Several criteria
      were tested for their ability to predict the long-term visual field preservation.
      RESULT: The best correlation was obtained by a combined criterion specifying both
      an absolute upper limit and a relative IOP decrease (i.e. IOP postoperatively <
      0.8*IOP preoperatively and IOP postoperatively < 21 mmHg). CONCLUSION: We
      recommend use of this criterion whenever the effect of a pressure-lowering
      operation has to be estimated shortly after surgery.

PMID- 9004885
TI  - [Localization of cAMP-selective phosphodiesterase in the mammalian eye by (3H)
      rolipram].
AB  - It has been shown that inhibition of phosphodiesterase (PDE) or an increase in
      intracellular cyclic adenosine monophosphate (cAMP) can lower the intraocular
      pressure in mammalian eyes. The PDE inhibitor rolipram binds with high affinity
      to a cAMP-dependent PDE. In the following study, receptors for rolipram in the
      mammalian eye are determined by autoradiography. About 1050 histological sections
      of rabbit (albino and pigmented), rat, monkey (baboon and marmoset) and human
      eyes were examined concerning rolipram-binding sites in different structures. The
      highest specific binding of rolipram to the ciliary body epithelium was seen in
      human, rabbit and baboon eyes. Marmoset eyes showed the highest specific binding
      in the ciliary body muscle, rat eyes in the retina. Specific binding was
      consistently high in the ciliary body epithelium and therefore at the site of
      aqueous humor formation. Because of these results and the known mode of action of
      rolipram, one can assume a close connection between rolipram-binding sites and
      the regulation of intraocular pressure.

PMID- 9004888
TI  - [New communication media for ophthalmology].
AB  - BACKGROUND: The use of high-tech communication is undoubtedly growing and has
      become established in almost all sciences and research fields. This article
      surveys the possibilities for scientific data-exchange via the Internet, the
      world's largest computer network. METHODS: An introduction is given to network as
      a whole, its history and structure, and the hardware and software required.
      Examples are provided to describe the basic services on the Internet with special
      emphasis on World wide web applications. CONCLUSIONS: The paper indicates that
      the Internet has a vast potential for providing almost unlimited information of
      relevance to users. By using the Internet and its resources, modern
      ophthalmological research will become more effective and successful.

PMID- 9004889
TI  - [Noise field screening. Results of a television field study for detection of
      visual field defects].
AB  - White noise field campimetry is able to transform usually negative scotomas
      immediately into perceivable visual field defects. As this method needs a
      monitor, the obvious solution was to evaluate the suitability of the noise field
      stimulus broadcasted to home TV sets. Therefore, in cooperation with the
      "Suddeutscher Rundfunk" (SDR) as well as several health insurance companies ("AOK
      Baden-Wurttemberg" and other "RVO-Kassen"), approximately 300,000 viewers were
      invited to take this test after receiving brief information and instruction.
      There were 531 calls for questionnaires to document the subjects' findings and
      the results of a subsequent ophthalmological examination. In most cases this
      clarified the perceived noise field defect. Out of 127 evaluable questionnaires,
      78 cases did not show any relevant ophthalmological pathology; this held true
      especially for lesions of the visual pathway. However, in 49 persons the
      ophthalmologists detected pathological findings; in 20 of these, the scotomas
      were previously unknown to the physicians. Glaucomatous optic neuropathy and
      macular degeneration were most frequently diagnosed as causing the white noise
      field defects. Finally, some preliminary estimates of the costs and benefit of
      this study are presented.

PMID- 9004892
TI  - [Limbus stem cells and their significance for regeneration of of the corneal
      surface].

PMID- 9004891
TI  - [Microsurgical transconjunctival approach to the orbits. Initial retrospective
      analysis of experiences with the transconjunctival approach in 15 patients.
      Clinical and surgical aspects].
AB  - The authors report 4-year follow-up results for their first 15 consecutive tumor
      patients, who underwent transconjunctival surgery of their orbital lesions
      without muscle dissection. Presentation, natural history, management, surgical
      appraisal of the transconjunctival approach and its indications are discussed. At
      follow-up, 14 of the patients showed excellent cosmetic and functional results.
      Our experience with the transconjunctival approach in the past 4 years suggests
      that this approach remains a useful modality, with good intraoperative visibility
      and minimal postoperative scar formation, for managing selected patients with
      space-occupying lesions located in the inferior medial and basal compartment of
      the orbit. Not suitable for the transconjunctival approach are deep intraconal
      lesions (orbital apex) and extraconal superior lesions. The rare problems with
      the transconjunctival approach have included temporary eye muscle injury with
      ophthalmoplegia postoperatively. More recently, the use of the transconjunctival
      approach has allowed surgeons to reduce cosmetic failures, functional deficits
      and deformities of the orbit. Because of its low risks, the absence of
      postoperative bleeding, and the absence of prolongation of hospitalization or
      immobilization of the patients, the transconjunctival approach is a successful
      procedure, especially in elderly multimorbid patients.

PMID- 9004890
TI  - [Dermal fatty tissue transplant as primary and secondary orbital implant.
      Complications and results].
AB  - In this retrospective study we report the indications, complications and
      functional and cosmetic results after dermofat grafting into anophthalmic orbits.
      The method consists of implantation of autogenous dermis with attached
      subcutaneous fat from the gluteal region into the orbit. Twenty-four primary and
      4 secondary grafts were implanted in 28 patients aged 12 to 49 years. In the
      explantation site one patient showed delayed healing. All implants became
      integrated, none were lost because of infection or extrusion. Eleven patients
      developed minor complications like central ulceration in the dermis, hair growth
      on the dermis or suture granuloma. In the primary implant group the functional
      and cosmetic outcome was evaluated by measurements of the lid structures,
      exophthalmometry (Hertel) and measuring the prosthesis motility (Kestenbaum).
      Three patients showed fair results; all the others had good or very good results.
      In one case of a secondary implant marked graft atrophy was observed. Despite the
      more extensive surgery and some minor complications the safety of this method
      with good functional and cosmetic results makes dermofat grafting an excellent
      alternative to heterogeneous orbital implants.

PMID- 9004893
TI  - [Agitation in the elderly person. Diagnostic and therapeutic approach].
AB  - Treating agitation in elderly people is a complex process. Faced with a paucity
      of empirical information, clinicians tend to adopt a therapeutic approach based
      on their clinical evaluation. This article offers a rational approach that will
      help physicians to better understand, evaluate, and treat agitation.

PMID- 9004895
TI  - [A comparison of the antibacterial activity of the parasporal bodies of different
      bacilli].
AB  - Solutions of the parasporal bodies of Bacillus sphaericus, B. laterosporus, and
      several B. thuringiensis subspecies display antibacterial activity showing the
      potential of membranotropic action of the body proteins. Comparison of the
      antibiotic effect of various delta-endotoxins of B. thuringiensis made it
      possible to identify highly active unique proteins. This approach forms the basis
      of goal-directed search for organisms sensitive to polypeptides of various
      bodies. It has already been established that delta-endotoxins of B. thuringiensis
      ssp. amagiensis cause the death of representatives of the fourth (in addition to
      the three previously known) order of insects, Isoptera.

PMID- 9004894
TI  - [Gangliosides synchronize the rhythm of protein synthesis in hepatocytes in
      vitro].
AB  - The kinetics of protein synthesis was studied in the cultures of rat hepatocytes
      on slides covered with collagen or fibronectin and kept in a serum-free medium
      199 complemented by albumin and insulin. No protein synthesis rhythm was found in
      the cultures with markedly separated cells obtained from a diluted suspension of
      hepatocytes ("sparse cultures"). After 0.3-0.4 microM total gangliosides were
      added to the medium with such cultures, the rhythm was found in all experiments.
      Such an effect was earlier found under the influence of a medium conditioned by a
      monolayer on the sparse cultures. The results obtained suggest the involvement of
      gangliosides in synchronization of oscillations of the protein synthesis
      intensity and call for studies of the conditioned medium properties.

PMID- 9004896
TI  - [Medicinal plants--concentrators of chromium. The role of chromium in alkaloid
      metabolism].
AB  - Mass screening of medicinal plants of the flora of Russia (196 species) was
      performed for chromium content. A total of 124 species-chromium concentrators
      were found, in which the chromium content markedly exceeded the mean values, this
      excess being 4- to 6-fold in 54 species, 7- to 3-fold in 62 species, and 37- to
      114-fold in seven species. The greatest capacity of chromium accumulation was
      shown for the sand immortelle, foxglove, Alexandrian laurel, Greek valerian,
      marsh cudweed, adenostilis, and lobelia. These species are considered as
      potential sources of chromium for correction of its deficiency in humans. Some
      mechanisms underlying the effect of chromium on metabolism of alkaloids
      derivative of quinolizidine, tropane, isoquinoline, and indole, were deciphered.

PMID- 9004897
TI  - [The recognition by European lynxes (Lynx lynx, Felidae, Carnivora) through
      urinary odor signals of the species, sex and age of conspecific, familiar and
      unfamiliar individuals].
AB  - The informative importance of urinary odors, which has virtually not been studied
      in the wild Felidae, was evaluated in European lynxes kept in captivity. The
      behavior of lynxes during examination of urine samples was described. The
      frequency and duration of all reactions were recorded: smelling, flehmen, and
      rubbing on urine. Significant differences in the reactions to the urine samples
      were most frequent as concerns the duration of smelling. Sexually mature
      recipient lynxes distinguished the species (lynx or domestic cat) and sex and age
      (sexually mature of young) of conspecific individuals and recognized individual
      urine samples. Presentation of the frozen samples did not increase the duration
      of any reaction. The role of urine in chemocommunication of lynxes is discussed.

PMID- 9004898
TI  - [The reaction of adult Roborovskii dwarf hamsters (Phodopus roborovskii) to the
      odor signals of individuals of their own and the opposite sex at different
      seasons of the year].
AB  - Studies were carried out on adult males and females of the Roborovskii dwarf
      hamster kept in natural temperature and light regime throughout the year. The
      reactions of hamsters to odors of urine, excrements, and the secretory substance
      of the midabdominal gland from conspecific males and females were studied by the
      method of alternative selection from a pair of presented odor sources during each
      of the four seasons. The results obtained were compared with reproduction in the
      tested individuals. It was shown that interest in the same excrements changed in
      different seasons, urine being the most sexually attractive. However, if the
      males examine this odor from the opposite sex reliably longer during all seasons,
      the females show a similar picture only in spring-summer, which coincides with
      the most active reproduction. Unlike the urine, the secretory substance of the
      midabdominal gland appears to have greater importance in organization of the
      territorial interactions between individuals. Both males and females smell the
      secretory substance of the donor males reliably longer during all seasons, except
      winter. Feces do not play the leading role either in sexual or territorial
      interactions, but interest in the odor of this excrement in individuals of both
      sexes is sufficiently high, especially in summer.

PMID- 9004899
TI  - [The protective effect of a NO-synthase inhibitor in heat shock].
AB  - Acute hypotension related to the excessive production of a potent endogenous
      vasodilator nitric oxide (NO) is a most important link of heat shock
      pathogenesis. It was shown that inhibition of inducible NO-synthase by N(W)-nitro
      L-arginine (L-NNA) at 10 mg/kg reduces the mortality of animals due to heat
      shock, prevents the fall of arterial blood pressure and abnormal inhibition of
      constriction and stimulation of dilation reactions related to NO hyperproduction.
      A total blockade of NO synthesis by L-NNA at 300 mg/kg did not exert a protective
      effect from heat shock. The data obtained suggest the importance of inducible NO
      synthase in heat shock pathogenesis and show promise for the application of
      selective inhibition of inducible NO-synthase at pathological states related to
      NO hyperproduction.

PMID- 9004900
TI  - [Viral evolution: the development of the ecological trend in research].
AB  - A review of the main development stages of important components of the concept of
      viral evolution and ecological trends is given. The periods are distinguished by
      the time of discovery and studies of physicochemical and molecular genetic
      properties of the viruses, as well as the logic of penetration of general biology
      and ecology ideas in virology. On the basis of these processes, specific
      fundamental and applied problems were formulated and developed. Special attention
      is paid to transmission and preservation of viruses in populations, the role of
      civilization in development of novel infections, horizons, pathways of
      prophylaxis and future control of viruses.

PMID- 9004902
TI  - [Hissing--a multifunctional and interspecific animal signal].
AB  - Hissing signals were studied in various groups of animals: insects, reptiles,
      mammals, and birds. Hissing was analyzed using a computer-based acoustic analyzer
      KAPROS-01. General similarities of hissing were noted for representatives of
      taxonomically remote orders and classes, as well as evident structural
      differences, not always related to the absence of taxonomic relatedness of the
      given species. Bioacoustic parallelisms of hissing were shown, which are based on
      threatening signals from animals with ecological weapons, such as poison, sharp
      teeth and claws, etc. Multifunctional and interspecific patterns of hissing were
      noted as well as its ecological-communicative role in biocenotic relations
      between animals of different groups.

PMID- 9004901
TI  - [Changes in the functional status of the hemostatic system with the
      administration of heparin combined with aspirin to animals with experimental
      diabetes].
AB  - It was shown that in the case of regular intragastric introduction of heparin
      combined with aspirin to rats with insulin-dependent experimental diabetes,
      enzymatic and nonenzymatic fibrinolysis of blood plasma was enhanced. The blood
      level of sugar was normalized in these animals.

PMID- 9004903
TI  - [Structure of blood flow in the left ventricle and aorta using the analytical
      solutions of nonstationary hydrodynamics equations and morphometric study].

PMID- 9004904
TI  - [Structural mechanisms of resistance to cerebral ischemia in rats with different
      types of behavior].

PMID- 9004906
TI  - [Conditioning in neuronal populations of intact cerebral cortex and in isolated
      neuronal strips].

PMID- 9004905
TI  - [Endothelin-1 modulates acetylcholine-induces relaxation of isolated rat aorta].

PMID- 9004907
TI  - Comparison of the targeting characteristics of various radioimmunoconjugates for
      radioimmunotherapy of neuroblastoma: dosimetry calculations incorporating cross
      organ beta doses.
AB  - To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody
      radioisotope combinations should be used to deliver the highest tumor and the
      lowest normal tissue doses. In a mouse model, tumor and critical organ-absorbed
      doses delivered by different radioimmunoconjugates were calculated and compared.
      We used a Medical Internal Radiation Dosimetry (MIRD)-style mouse dosimetry model
      that incorporates cross-organ beta doses to make refined estimates of the
      radiation absorbed dose to tissues. Biodistribution data from neuroblastoma
      xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed
      dose values for 90Y-3F8, 131I-3F8 and 131I-F(ab')2 fragments. Immunoreactive
      fractions of the radiolabeled antibodies were comparable. Although tumor uptake
      of the radioiodinated and radiometal labeled 3F8 was much higher than that of the
      radioiodinated F(ab')2 fragments (maximum percent injected dose per gram values
      were 39.4, 33.2 and 20.1 for 131I-3F8, 90Y-3F8 and 131I-F(ab')2, respectively),
      tumor to nontumor ratios were higher for radioiodinated fragments (with the
      exception of tumor to kidney ratio). For the minimum tumor dose necessary for
      complete ablation, the bone marrow received 195, 278 and 401 cGy for 131I
      F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor doses were 50.1, 232 and 992
      cGy/MBq for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor to bone
      marrow dose, which is defined as the therapeutic index, was 21.5, 14.7 and 10.4
      for 131I-F(ab')2, 131I-3F8 and 90Y-3F8. 131I-F(ab')2 fragments produced the
      highest therapeutic index but also the lowest tumor dose for radioimmunotherapy.
      Radiometal conjugated IgG produced the highest tumor dose but also the lowest
      therapeutic index.

PMID- 9004908
TI  - Co production of 2,6-[18F] difluoroDOPA during electrophilic synthesis of 6
      [18F]fluoro-L-DOPA.

PMID- 9004909
TI  - Development of labeled thymidine analogs for imaging tumor proliferation.
AB  - We have sought nucleoside analogs suitable for labeling with F-18 that could be
      used to image tumor proliferation with positron emission tomography (PET). The
      following three thymidine analogs were labeled with tritium and screened for
      their catabolism and biodistribution in vivo in mice: 5-fluoro-1-(2'-deoxy-2'
      fluoro-beta-D-ribofuranosyl)uracil (FFUdR), 5-fluoro-1-(2'-deoxy-2'-fluoro-beta-D
      arabinofuranosyl)-uracil (FFaraU) and 5-methyl-1-(2'-deoxy-2'-fluoro-beta-D
      ribofuranosyl)uracil (FTdR). We found that all three compounds were stable to
      degradation in vivo and when incubated in blood. Of the three analogs tested,
      only FFUdR showed preferential retention in rapidly proliferating tissues, such
      as the spleen and implanted tumors, and it attained tissue to blood ratios of 2.1
      at 2 h.

PMID- 9004910
TI  - Synthesis and evaluation of [123I]-iodo-PK11195 for mapping peripheral-type
      benzodiazepine receptors (omega 3) in heart.
AB  - An iodinated analog of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1
      methylpropyl)isoquinoline-3-carboxamide , a specific antagonist of the peripheral
      type benzodiazepine receptor (omega 3), has been synthesized in three steps with
      an overall chemical yield of 40%. Both [123I]- and [125I]-Iodo-PK11195 have been
      synthesized by solid-state isotopic exchange in > 60% isolated radiochemical
      yield and specific activity of 233-348 mCi/mmol. Tissue distribution studies in
      rats indicate a high uptake of radioactivity in adrenal glands, heart, lung and
      kidneys, which was blocked 63-87% by preadministration of cold PK11195. Single
      photon emission computer tomography (SPECT) imaging of the canine heart has been
      accomplished with [123I]PK11195. These results suggest that [123I]PK11195 has
      potential as a SPECT radiotracer for studying the omega 3 receptor in humans.

PMID- 9004911
TI  - Inflammation-seeking scintigraphy with radiolabeled biotinylated polyclonal IgG
      followed by the injection of avidin chase.
AB  - We tried to apply the avidin chasing system to the inflammation-seeking
      scintigraphy using radiolabeled nonspecific polyclonal IgG. We studied the
      pharmacokinetics of technetium-99m and iodine-125-labeled biotinylated murine
      polyclonal IgG followed by an avidin chase injection in model mice with
      inflammatory foci. Avidin chase decreased the circulating radioactivity of 99mTc
      and 125I, which was a major problem for inflammation-seeking scintigraphy using
      radiolabeled nonspecific polyclonal IgG, to 9.3% and 19.3% of that without an
      avidin chase injection, respectively. Inflammation-seeking scintigraphy with the
      aforementioned method would be better than that with conventional method.

PMID- 9004912
TI  - An Rh-105 complex of tetrathiacyclohexadecane diol with potential for formulating
      bifunctional chelates.
AB  - 1,5,9,13-Tetrathiacyclohexane-3,11-diol (16S4-diol), a sulfur crown ether analog,
      was studied as a potential chelating agent to complex no-carrier-added (NCA)
      grade 105Rh(III) in high yield at low ligand concentrations. trans-[RhCl2(16S4
      diol)]chi (chi = Cl, PF6) was prepared using nonradioactive RhCl3.3H2O and
      characterized by UV-Vis, nuclear magnetic resonance (NMR) and X-ray
      crystallography. It was shown to have a +1 charge with the Rh(III) metal center
      coordinated to the four S atoms equatorially and two Cl atoms in trans axial
      positions. The 105Rh-16S4-diol complex prepared with NCA 105Rh(III)-chloride
      reagent was found to exhibit identical chromatographic properties as trans
      [Rh(III)Cl2(16S4-diol)]+ (including silica and C-18 thin-layer chromatography
      [TLC] and electrophoresis). The preparation of 105Rh-16S4-diol complex formation
      optimized for conditions of pH, temperature, time, % ethanol and quantity of 16S4
      diol resulted in yields > 90%. Very low quantities of 16S4-diol (3 nmol) complex
      NCA 105Rh(III) under relatively mild reaction conditions (heating at 64 degrees C
      for 90 min) in the presence of ethanol (10%), yielded the high specific activity
      105Rh-16S4-diol complex as a single cationic species. The 105Rh-16S4-diol complex
      was shown to be stable for > or = 4 days in physiological buffers at room
      temperature and in human serum at 37 degrees C.

PMID- 9004913
TI  - Direct radiofluorination of dopamine: 18F-labeled 6-fluorodopamine for imaging
      cardiac sympathetic innervation in humans using positron emission tomography.
AB  - Fluorine-18 labeled fluorodopamine (FDA) was synthesized by the direct
      fluorination with [18F]F2 [produced by the nuclear reaction 18O(p,n)18F] of
      dopamine in anhydrous hydrogen fluoride containing boron trifluoride at -65
      degrees C. Reverse-phase high-performance liquid chromatography (HPLC) was used
      to separate [18F]6-FDA from the reaction mixture containing 18F-labeled 2- and 5
      FDA. The radiochemical yield of [18F]6-FDA, with respect to [18F]F2, was 10 +/-
      2% at the end of the 120-min synthesis from EOB1. The specific activity of [18F]6
      FDA at the end of synthesis, 10 +/- 1.5 Ci/mmol, is sufficiently high that the
      amount of 6-FDA associated with the infusion of a dose of 5 mCi of [18F]6-FDA
      over 3 min into a 50-kg human (0.5-0.7 microgram/kg/min) is considerably lower
      than therapeutic doses (2-10 micrograms/kg/min) of dopamine.

PMID- 9004914
TI  - [18F]haloperidol binding in baboon brain in vivo.
AB  - The binding of [18F]haloperidol to dopamine D2 and to sigma recognition sites in
      baboon brain was examined using positron emission tomography (PET). Studies were
      performed at baseline and after treatment with either haloperidol (to evaluate
      saturability), (+)-butaclamol (which has specificity for dopamine D2 receptors)
      or (-)-butaclamol (which has specificity for sigma sites). Binding was
      widespread. Treatment with (-)-butaclamol had no effect, whereas (+)-butaclamol
      selectively reduced the uptake in striatum. Haloperidol increased the clearance
      rate from all brain regions. These results indicate that the binding profile of
      [18F]haloperidol does not permit the selective examination of either dopamine D2
      or sigma sites using PET.

PMID- 9004915
TI  - Biological studies of analogues of glucose iodinated in positions 1, 2, or 3.
AB  - Analogues of glucose labeled with 123 iodine in positions 1, 2 or 3 have been
      synthesized. The aim of this study was to examine their biological behavior in
      four experimental models in order to assess whether they could be used to
      evaluate the uptake of glucose with single photon emission computed tomography
      (SPECT). The results obtained have shown that none of these molecules enters the
      cell using the glucose transporter. Therefore, they cannot be used as tracers of
      glucose uptake.

PMID- 9004916
TI  - Radiotracer binding to brain microsomes determined by thin-layer chromatography.
AB  - A thin-layer chromatography (TLC) assay was developed to monitor the interaction
      of radiotracers with brain microsomes. Murine brain microsomes were coated onto a
      zone of a TLC strip, the unreacted sites blocked with gelatin, and the
      radiotracers chromatographed over the microsomes. Radiotracers bound to the
      microsomes and were separated from the unreacted materials which migrated at or
      near the solvent front. Up to 80% of the applied radioactivity bound to the brain
      microsomes when using 99mTc-(d,l) hexamethyl-propyleneamine oxime (HMPAO) and
      123I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl]-benzamide
      (123I-IBZM) as tracers. On the other hand, the presumptive negative control
      materials p-I-15-phenyl-pentadecanoic acid-123I (123I-IPPA) and 99mTc-mercapto
      acetyl triglycine (MAG3) bound poorly (7% and 4%, respectively). 99mTc-ethyl
      cysteinate dimer (ECD) interacted poorly (9.9%), a result thought to be
      consistent with its known inability to be metabolized by nonprimate brain tissue.
      Radiolabeled octreotide analogues (radiolabeled with 111In, I-131 or 99mTc) also
      bound, and the binding could be reduced by excess unlabeled octreotide. Also,
      chemical modification by acylation of Lys5 in 111In-labeled octreotide led to
      decreased binding (approximately 70%) compared to the original radiotracer.
      Chromatography of the various radiotracers over TLC strips coated only with
      gelatin was used to monitor nonspecific binding and was low and frequently below
      5%. This technique does not require wash steps or centrifugation, and assays are
      rapidly completed. The assay could be useful in monitoring the interaction of
      radiotracers with brain microsomes and in evaluating and developing new
      radiotracers.

PMID- 9004917
TI  - Radioimaging of human breast carcinoma xenografts in mice by [123I]-labeled Z-17
      alpha-iodovinyl-11 beta-chloromethyl-estradiol.
AB  - Z-17 alpha-iodovinyl-11 beta-chloromethyl-estradiol (Z-CMIV), a new selective
      estradiol derivative, can easily be labeled with high efficiency by radioactive
      iodine isotopes. Biodistribution studies and quantitative scintigraphic imaging
      of human breast carcinoma xenografts in mice demonstrated continuous and
      selective accumulation of the [123I]Z-CMIV, in estrogen receptor (ER)-positive
      target tumors, with significantly high target/nontarget ratio up to 48 h post
      injection. A receptor-mediated mechanism of concentration of Z-CMIV in target
      tissues was confirmed by scintigraphic imaging and by biodistribution studies.

PMID- 9004918
TI  - Is TISCH a suitable tracer for in vivo study of modifications of the dopamine D-1
      receptor?
AB  - To detect quantitative modification of dopamine D-1 receptors in vivo, we used
      [125I]-TISCH in an animal modelin which the striatum was unilaterally lesioned
      with quinolinic acid. [125I]-TISCH was injected into rats 5 days after the
      lesion, and the changes in receptor density obtained in vivo were compared to in
      vitro quantification of dopamine D-1 receptors by binding with either [125I]
      TISCH or [3H]-SCH 23390 as a reference ligand. In vivo and in vitro, we obtained
      the same decrease (-70%) in binding of these ligands in the lesioned striatum.
      Using an injection of [99mTc]-DTPA to lesioned rats, we also showed the
      disruption of the blood-brain barrier (BBB) in the lesioned area. Thus, the
      equivalent decrease observed in vitro and in vivo with [125I]-TISCH confirmed
      that this molecule would be a valuable tool for exploration of dopamine D-1
      receptors by SPECT imaging. Moreover, the fact that the breakdown of the BBB did
      not interfere with the receptor binding obtained in vivo may be important for
      future investigations in pathologies with BBB disruption, such as ischemia.

PMID- 9004919
TI  - A new approach to labeling cells with technetium-99m, Part I. Preparation of
      modified polylysine and in vitro cell labeling.
AB  - A method for labeling cells with technetium-99m via hydrophilic, polycationic
      poly D-lysine modified by N-acetyl homocysteine has been developed. The modified
      polylysine (MPL) is labeled with 99mTc in > 95% yield and is stable for > 12 h.
      Maximum cell labeling is achieved by a 1-h incubation at room temperature with
      isolated leukocytes, granulocytes and peripheral blood mononuclear cells
      attaining 60-75% 99mTc incorporation, and red blood cells 35%. Ninety-two percent
      of the label is retained by leukocytes after a 1-h incubation at room temperature
      in 50% serum. The cell uptake of 99mTc-MPL is affected by the presence of
      negatively charged species in the medium; the inhibitory effects of 5% serum or
      serum albumin can be reversed by increasing the concentration of 99mTc-MPL, while
      those of heparin are not.

PMID- 9004921
TI  - Human biodistribution and dosimetry of the SPECT D2 dopamine receptor radioligand
      [123I]IBF.
AB  - The research discussed in this article aimed to characterize better the
      biodistribution, excretion and radiation dosimetry of the single photon emission
      computed tomography (SPECT) D2 Dopamine receptor radioligand [123I]IBF. Following
      administration of 111 +/- 12 MBq [123I]IBF, seven healthy human subjects were
      scanned serially with a whole body imager over a 48-h period. Transmission images
      were obtained with a scanning line source for attenuation correction of the
      emission images. Urine was collected for 48 h to measure the fraction of activity
      voided by the renal system. Radiation absorbed dose estimates were performed
      using biokinetic modeling and the Medical Internal Radiation Dose (MIRD) schema.
      Highest absorbed doses were to the kidney (0.13 +/- 0.02 mGy/MBq) and urinary
      bladder wall (0.11 +/- 0.01 mGy/MBq). The effective dose equivalent was 0.041 +/-
      0.005 mSv/MBq. Peak brain uptake represented 8% of the injected activity. Rapid
      urinary excretion minimized the absorbed dose to most tissues. The mean
      cumulative urinary excretion fraction was 69%. Thus [123I]IBF is a promising
      SPECT agent for imaging the D2 dopamine receptor in humans with high brain uptake
      and favorable dosimetry.

PMID- 9004920
TI  - A new approach to labeling cells with technetium-99m, Part II. Evaluation of
      radiolabeled human-lymphocyte immune functions.
AB  - Technetium-99m-modified polylysine (MPL) is a mild and efficient method for cell
      labeling that is easily applicable to human lymphocytes. 99mTc-MPL uptake is
      maximal in 40 min at room temperature. Cell labeling efficiency (from 60 to 80%)
      increases with rising concentrations of cells and labeling agent. In vitro
      stability of 99mTc-MPL on lymphocytes incubated in serum at 37 degrees C is high.
      Microautoradiography indicates that 99mTc-MPL is equally distributed within the
      cells. The radiolabeling procedure does not alter expression of surface receptors
      involved in T lymphocyte effector functions, adhesion function, cytolytic
      activity or proliferative response to IL-2.

PMID- 9004922
TI  - Pharmacokinetic studies of 131I-stevioside and its metabolites.
AB  - 131I-STEVIOSIDE (1.10 MBq) was injected i.v in Wistar male rats, in distribution
      in the body and metabolism were studied. The highest concentration of
      radioactivity was observed in the liver and in the small intestine after 10 and
      120 minutes, respectively. At 2 h after injection, the radioactivity eliminated
      in the bile was 52.0% of the original dose. The results of RP-HPLC analysis of
      the bile showed that stevioside was degraded in vivo and that steviol appeared as
      a major metabolite. However, in the urine; RP-HPLC analysis did not show the
      presence of steviol.

PMID- 9004923
TI  - [Perspectives in the rehabilitation of vision in blind subjects].
AB  - The normal development of the visual system from birth until the end of the
      critical period involves, for the young subject to achieve a number of visual
      experiments. In cases of late blindness, the visual system has been normally
      developed, which is not the case when early blindness is considered where an
      abnormal cerebral organization exists. Accordingly, attempts to rehabilitate
      vision in the blind have to consider these discrepancies. When the invasive
      visual prosthesis acting by electrical stimulation of spared parts of the visual
      system is suitable in case of late blindness, sensory substitution prostheses
      coding visual information into signals addressing an intact sensory modality
      seems devoted to cases of early blindness. This later approach takes into account
      the early blind's brain specific organization, whose undeveloped occipital cortex
      has been shown to be involved in the sensory substitution process using positron
      emission tomography.

PMID- 9004924
TI  - [Pharmacological study of neuroreceptors and implications in neurological and
      psychiatric therapeutics].
AB  - Neuroreceptors may be regulated by their mediators or by agonists, in order to
      reduce the sensitivity of target cells. The mechanisms of this regulation differ
      according to the cell type, the intensity and duration of the stimulation. Rapid
      desensitization may be due to different molecular modifications (conformational
      changes of ionic channels, phosphorylation, affinity change, reduced efficiency
      of the coupling with the second messenger...) and may be followed by receptor
      internalization, recycling (reappearance of the receptors at the cell surface) or
      degradation when the stimulation is long lasting. The use of different cell
      types, including transfected cells, and the study of different receptor sub
      types, allowed to better characterize the regulation processes and the effects of
      drugs on these mechanisms.

PMID- 9004925
TI  - [Transgenic models of human thyroid pathologies: hyperfunctional adenoma,
      anaplastic cancer, differentiated cancer, hypothyroidism].
AB  - Bovine thyroglobulin gene upstream regulatory sequences were used as a tissue
      specific promoter in order to direct the expression of different genes
      specifically to the thyroid gland. Transgenic models of thyroid diseases have
      been generated, by directing the expression of specific oncogenes to the thyroid
      cell. In one of these models (TgAgT), the sv40 large T antigen promoted the
      development of an aggressive undifferentiated tumor mimicking the phenotype of
      the human anaplastic carcinoma. In the second model (TgA2aR), the expression of
      the adenosine A2 alpha receptor, acting as a constitutive activator of adenylyl
      cyclase, resulted in the development of a hyperfunctioning goiter, and in old
      animals to the formation of malignant foci. Transgenic lines expressing the E6
      oncogenic (TgE6) from type 16 human papillomavirus appeared to be asymptomatic.
      In contrast, the thyroid cells of mice expressing E7 oncogene divide very
      rapidly, but remain differentiated, resulting in the development of huge colloid
      goiters. Signs of malignancy appear late in the development. The molecular
      properties of E6 and E7 oncogenes are to bind, and inactivatc, the tumor
      suppressor gene producers p53 (E6), or RB (E7). Our transgenic models indicate
      that the RB protein (and/or related proteins) are essential factors in the
      negative control of thyroid cell proliferation. On the contrary, inactivation of
      p53 seems to play a minor role, at least in the early steps of tumor formation.
      In the last model (Tg alpha 1B), the expression of a mutant of the alpha 1B
      adrenergic receptor reported to activate both CAMP and sigma P3-CA-cascades,
      resulted in growth stimulation, hyperfunction, cell degeneracy attributed to the
      overproduction of free radicals and malignancy.

PMID- 9004926
TI  - [Hierarchy of cellular regulation in the kidney].
AB  - Among the numerous "signals" which may alter the functional state of renal
      epithelial cells, it appears convenient to distinguish two categories: under
      physiological conditions, on the one hand, "hormones" control the rate of
      specific transport across their respective kidney target cells. In order to under
      stand how such cellular effects of hormones may contribute to maintain body fluid
      homeostasis, it is necessary to determine where and how each of them modifies the
      tubular fluid composition along the successive portions of the whole nephron;
      under pathological conditions or during kidney ontogenesis, on the other hand, a
      variety of "factors" present in the close environment induce, in kidney cells,
      functional programmes which favor either survival, growth, or division.

PMID- 9004927
TI  - Combined potentiating effect of byakko-ka-ninjin-to, its constituents, rhizomes
      of Anemarrhena asphodeloides, tomosaponin A-III, and calcium on pilocarpine
      induced saliva secretion in streptozocin-diabetic mice.
AB  - The effects on pilocarpine-induced saliva secretion by a hot aqueous extract of
      Byakko-ka-ninjin-to (BN), its constituents, rhizomes of Anemarrhena
      asphodeloides, three saponins (pseudoproto-timosaponin-AIII (An-S-1), proto
      timosaponin-AIII (An-S-2) and timosaponin-AIII (An-S-3)) and calcium were
      examined in streptozocin (STZ)-induced diabetic and normal mice. The hot aqueous
      extracts of BN (250 and 500 mg/kg, i.p.) and Anemarrhena (170 and 340) mg/kg,
      i.p.) significantly promoted salivary flow in the diabetic animals, but
      suppressed it in the normal controls. An-S-2 and An-S-3 but not An-S-1 (10 mg/kg,
      i.p.), significantly promoted salivary How in the diabetic animals. The potency
      order was An-S-3 >> An-S-2 >> extract. The hot aqueous extracts of BN and
      Anemarrhena increased the protein content of saliva in a dose-dependent manner.
      Combination of An-S-3 (0.1 mg/kg, i.p.) with CaCl2 (2 and 4 mg/kg, i.p.)
      potentiated salivary flow compared with the respective effect of each on its own.
      These results demonstrated that 1) An-S-3 was mainly responsible for saliva
      secretion of the hot aqueous extract, and 2) the effect of An-S-3 was potentiated
      by combination with calcium, suggesting combined effects of Byakko-ka-ninjin-to
      containing Anemarrhena asphodeloides and gypsum fiber (calcium).

PMID- 9004928
TI  - Inhibition-of-return at multiple locations in visual space.
AB  - Inhibition-of-return is thought to be a visual search phenomenon characterized by
      delayed responses to targets presented at recently cued or recently fixated
      locations. We studied this inhibition effect following the simultaneous
      presentation of multiple location cues. The results indicated that response
      inhibition can be associated with as many as four locations at the same time.
      This suggests that a purely oculomotor account of inhibition-of-return is
      oversimplified. In short, although oculomotor processes appear to play a role in
      inhibition-of-return they may not tell the whole story about how it occurs
      because we can only program and execute eye movements to one location at a time.

PMID- 9004929
TI  - Industrial accidents are related to relative body weight: the Israeli CORDIS
      study.
AB  - OBJECTIVES: The accident rate might be influenced by intrinsic characteristics of
      the workers, by risks inherent in the work environment, or a combination of these
      factors. As increased weight may be associated with sleep disturbances and
      fatigue, a high body mass index (BMI) might be an independent risk factor for
      accidents in industrial workers. METHODS: 3801 men were examined and followed up
      for two years for the occurrence of accidents. The objective environmental
      conditions were recorded and translated into a single score of ergonomic stress
      levels. Height and weight were recorded, as were possible confounding factors
      including measures of fatigue, type A personality, total night time sleep, job
      satisfaction, somatic complaints, smoking, and education levels. RESULTS: Both
      BMI and ergonomic stress levels independently predicted involvement in accidents
      (two or more) with those in the highest BMI quartile who worked in an environment
      with high ergonomic stress levels having a 4-6 times increased risk of accidents
      compared with those in the lowest BMI quartile who worked in an environment with
      low ergonomic stress levels (95% confidence interval (95% CI) 2.4-9.0, P <
      0.001). Although increasing somatic complaints and a low educational level also
      were predictors of accidents, they did not mediate the effect of the BMI on the
      accident rate. Increasing age, less smoking, and decreased sleep hours were
      significantly associated with an increased BMI, but the association of BMI and
      involvement in accidents also could not be explained by those factors or the
      other confounders. CONCLUSIONS: BMI independently influences the accident rate.
      Further studies warranted to confirm these findings and to explore mechanisms
      supporting biological plausibility.

PMID- 9004931
TI  - 19th International Symposium on Column Liquid Chromatography and Related
      Techniques. Part II. Innsbruck, Austria, 28 May-2 June 1995.

PMID- 9004930
TI  - Blood lead in pregnant women in the urban slums of Lucknow, India.
AB  - OBJECTIVES: To determine the concentrations of blood lead (PbB) in pregnant women
      in the slums of Lucknow, north India. METHODS: Of the 203 designated municipal
      slums in Lucknow, 70 were randomly selected for study and a cohort of 500
      pregnant women was enrolled. Each participant was interviewed with questions on
      possible sources of exposure to lead, surrogates of nutritional status were
      measured, and PbB was measured. RESULTS: The mean PbB was 14.3 micrograms/dl and
      19.2% of women had PbB > or = 20 micrograms/dl. PbB was not associated with age,
      height, weight, gestation, or history of abortions, although higher PbB was
      associated with higher parity. Women living inner city neighbourhoods near heavy
      vehicular traffic had PbB 2.2 micrograms/dl higher (95% confidence interval (95%
      CI) 0.8 to 3.6) than those living in other neighbourhoods. The PbB was not
      associated with reported use of piped water or the presence of paint in homes,
      and increasing PbB was unexpectedly associated with decreasing use of eye
      cosmetic "surma" and the duration of gestation. CONCLUSIONS: The high PbB found
      in this population raises concern about fetal development and points to the
      urgent need to reduce exposure to lead.

PMID- 9004933
TI  - Fully automated determination of selective retinoic acid receptor ligands in
      mouse plasma and tissue by reversed-phase liquid chromatography coupled on-line
      with solid-phase extraction.
AB  - A fully automated reversed-phase HPLC method was developed for the quantitative
      assay of three retinoids (Am-580, CD-2019 and CD-437) which selectively activate
      the retinoic acid receptors RAR alpha, RAR beta and RAR gamma, respectively.
      Mouse plasma, embryo and maternal tissues were prepared for injection by on-line
      solid-phase extraction (SPE) and valve-switching techniques. Following automatic
      injection, the sample was loaded on preconditioned disposable cartridges, cleaned
      up and then transferred onto the analytical column to be eluted in the backflush
      mode, separated by gradient elution and detected by UV, while a new cartridge was
      concomitantly conditioned. The overall recovery was quantitative allowing for
      external standardization. The calibration curves were linear in all biological
      samples tested so far, with a correlation coefficient (r) >0.99. The intra-day
      precision was < or = 7.8% (n = 5-6) and the inter-day variability was < or = 9.4%
      (n = 3). The lower limit of detection was 2.5 ng/ml or ng/g for CD-2019 and CD
      437, and 5 ng/ml for Am-580 with a S/N ratio of 5 using a sample weight of 25
      microliters or mg. The method is now in routine use in our laboratory for the
      assessment of the pharmacokinetic profiles of these retinoids. The small sample
      size required, the simple sample preparation and the rapid analysis with high
      degree of automation make this method convenient for microanalysis of biological
      samples both in animal and human studies.

PMID- 9004932
TI  - Analysis of recombinant human interleukin-11 fusion protein derived from
      Escherichia coli lysate by combined size-exclusion and reversed-phase liquid
      chromatography.
AB  - A two-dimensional size-exclusion-reversed-phase high-performance liquid
      chromatographic assay has been developed for the quantitation of recombinant
      human interleukin-11 fusion protein (rhIL-11 FP) expressed in E. coli cells. The
      sample preparation procedure included the optimization of lysis buffer components
      to achieve maximum rhIL-11 FP recovery through the disruption of associations
      between rhIL-11 FP and E. coli components. The E. coli cells were dialyzed into
      lysis buffer and lysed by a French Press prior to two-dimensional chromatographic
      analysis. A size-exclusion column was used first to remove high- and low
      molecular-mass E. coli components. Then reversed-phase chromatography was used to
      separate and quantify the rhIL-11 FP. The assay was linear over the range of
      0.0294 to 0.235 mg/ml. The limit of quantitation, 0.0294 mg/ml, was based on %
      normalized residuals and precision criteria not exceeding 10%. The
      reproducibility of the assay for lysate samples was good on a daily (% R.S.D. =
      1.0; n = 5) and a day-to-day reproducibility was good (% R.S.D. = 2.2; n = 9).
      Selectivity and chromatographic peak identification were based upon gel
      electrophoresis and N-terminal sequencing of the rhIL-11 FP peak collected from
      the reversed-phase column.

PMID- 9004934
TI  - Determination of fluvastatin enantiomers and the racemate in human blood plasma
      by liquid chromatography and fluorometric detection.
AB  - Liquid chromatographic methods for the determination of fluvastatin, as racemate
      and as separated enantiomers, are described. Fluvastatin was extracted at pH 6.0
      from blood plasma into methyl tert.-butyl ether. The organic phase was evaporated
      and the extract redissolved into either a phosphate buffer solution of pH 6.0
      containing tetrabutylammonium fluoride and methanol for the racemate
      determination, or in a mixture of acetonitrile and water for assaying the
      enantiomers. The absolute recoveries were 95 and 86% for the racemate and the
      enantiomers, respectively, and the limit of quantitation 0.5 nmol/1 for the
      racemate, and 5 nmol/l for the enantiomers, when using half a millilitre of
      plasma sample. The samples were chromatographed on a C8 column (racemate) and on
      a Chiralcel OD-R column (enantiomers), and monitored using fluorescence
      detection. In the achiral system, post-column exposure of the eluate to UV light
      enhanced the sensitivity by 4 to 5 times when compared with analysis based on the
      native fluorescence.

PMID- 9004935
TI  - Liquid chromatography studies on the enzymatic degradation of luteinizing hormone
      releasing hormone analogues with off-line identification by mass spectrometry.
AB  - Several agonists of luteinizing hormone-releasing hormone (LHRH) are currently
      used for different therapeutic purposes, but relatively little is known about
      their metabolic fate after administration. This paper describes the application
      of high-performance liquid chromatography combined with off-line fast atom
      bombardment mass spectrometry to identify the degradation products resulting from
      the incubation of LHRH analogues with proteolytic enzymes. Three analogues,
      containing a psi(E,CH = CH) pseudo-peptide bond were synthesized and afforded to
      the assay to determine the resistance against alpha-chymotrypsin and subtilisin:
      [Tyr5 psi(E,CH = CH)Gly6]LHRH, [Gly6 psi(E,CH = CH)D,L-Leu7]LHRH and [Pro9
      psi(E,CH = CH)Gly10 ]LHRH. The pattern of peptide metabolites identified by this
      method indicates that alpha-chymotrypsin degrades LHRH analogues at the Trp3-Ser4
      and Tyr5-Gly6 bond, while subtilisin hydrolyzes only the Tyr5-Gly6 linkage. The
      results also indicate a possible stabilization of native amide bonds against
      enzymatic degradation by neighbouring psi(E, CH = CH) modifications.

PMID- 9004936
TI  - High-performance liquid chromatography of peptides on a microspherical carbon
      column.
AB  - The properties of a microspherical carbon column for the separation of peptides
      and proteins are described. One hundred and thirty-three peptides, with from 1 to
      148 amino acid residues, were applied on a carbon column and eluted with a linear
      gradient of acetonitrile [10-70% (v/v), 30 min] in 0.1% (v/v) trifluoroacetic
      acid solution. The elution behaviour of the peptides on the carbon column and on
      an octadecylsilica (ODS) column were compared under the same elution conditions.
      Relationships between the logarithm of the hydrophobicity of peptides and their
      capacity factors were approximately linear on both columns, but some exceptions
      were observed with peptides with aromatic residues, indicating stronger
      adsorption on the carbon than on the ODS column. These results suggest that the
      major factor for the separation of peptides on both the carbon and ODS columns is
      hydrophobic interactions. The stronger adsorption of aromatic side-chains in
      peptides on the carbon column could be understood by an interaction based on the
      aromatic or graphitic nature of the surface of the microspherical carbon
      packings.

PMID- 9004938
TI  - Automated method for the measurement of amino acids in urine by high-performance
      liquid chromatography.
AB  - An automatic and sensitive HPLC method for the determination of primary and
      secondary amino acids included cystine and homocystine in urine samples is
      described. After a simple ultrafiltration, urine samples were subjected to
      reduction of disulfides, carboxymethylation of free thiols and double precolumn
      derivatization with o-phthalaldehyde-3-mercaptopropionic acid and 9
      fluroenylmethyl chloroformate. All reactions were fully automated by means of an
      injector programme and were accomplished in 10 min. Since urine samples contain a
      large number of amino compounds, a good resolution was required. By optimization
      of the conditions, separation of 40 amino acids in 92 min was achieved. The
      recovery of amino acids ranged from 83% for TRP to 105% for CIT. The within-run
      and between-run R.S.D.s of urinary amino acid concentrations were below 10% for
      most amino acids except for HYL, LYS and ORN. The method was applied to the
      diagnosis of genetic disorders of amino acid metabolism.

PMID- 9004937
TI  - Isolation and identification of peptide conformers by reversed-phase high
      performance liquid chromatography and NMR at low temperature.
AB  - Peptide conformers with one or more rotationally hindered peptide bonds due to
      the presence of proline and/or another N-substituted amino acid residue in the
      molecule were separated by reversed-phase chromatography at low temperatures,
      isolated and identified by NMR. The scope of this investigation included the cis
      trans isomers of the dipeptides Leu-Pro, Phe-Pro and Tyr-Pro as well as
      conformers of opioid peptides containing proline and/or the proline-like Tic
      (1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid) residues: Tyr-Pro-Phe (beta
      casomorphin 1-3 fragment), Tyr-Tic-Phe-Phe, Try-Pro-Phe-Pro-Gly (beta-casomorphin
      5), Tyr-Tic-Phe-Phe-Val-Val-Gly-NH2 and Tyr-Tic-Phe-Gly-Tyr-Pro-Ser-NH2.
      Chromatography with micropellicular and totally porous octadecylated silica
      stationary phases and aqueous methanol under isocratic elution conditions
      resulted in well separated peaks of the rotational isomers at sufficiently low
      temperatures. Preparative RP-HPLC was carried out with eluents containing water
      and methanol, both deuterated, and the effluent fractions containing each isomer
      were collected for further investigation. The conformational states of the
      peptide isomers upon separation were conserved by storing the effluent fractions
      in liquid nitrogen. The Leu-Pro, Phe-Pro, Tyr-Pro and Tyr-Pro-Phe conformers were
      identified by one- and two-dimensional NMR spectroscopy at -15 degrees C. Upon
      comparing the NMR spectra of the isomers, for these peptides the retention order
      of the conformers was unambiguously established: in each case the trans,
      conformer is eluted before the cis conformer. On the basis of NMR data obtained
      the beta-casomorphin-5, which contains two proline residues, the elution order of
      its four conformers was established by NMR spectroscopy of the fractions obtained
      by RP-HPLC at low temperature as trans-trans (least retained), trans-cis, cis-cis
      and cis-trans (most retained).

PMID- 9004939
TI  - Reference values of neuroactive amino acids in the cerebrospinal fluid by high
      performance liquid chromatography with electrochemical and fluorescence
      detection.
AB  - Sampling and HPLC analysis procedures for CSF amino acid determinations were
      evaluated. In order to increase sensitivity, a precolumn derivatization of amino
      acids by o-phthalaldehyde-mercaptoethanol reagent was used. By using fluorimetric
      and electrochemical detection in series, positive peak identification can be
      obtained in a single chromatographic run. It is recommended to analyze freshly
      collected CSF. Amino acids are stable for short periods over a wide range of
      temperature, but storage at -80 degrees C is recommended. The CSF samples for the
      calculation of the reference values were taken from 40 healthy subjects,
      hospitalized for lumbar disk herniation, placed on the same diet and kept drug
      free for at least 1 week. The mean values (mumol/l) and the ranges (in
      parentheses) were: 0.27 (0.09-0.63), 0.62 (0.18-1.15), 5.32 (3.05-11.50), 6.16
      (2.90-13.30), 0.16 (0.03-0.22) for aspartic acid, glutamic acid, glycine, taurine
      and gamma-aminobutyric acid respectively.

PMID- 9004940
TI  - Sample preparation for the determination of purine nucleotide analogues in
      tissues.
AB  - A sample treatment procedure for the determination of thiopurine and ganciclovir
      nucleotides in human tissues was developed. Owing to the lack of suitable
      standards for most of the active nucleotide analogues, the procedure was based on
      two steps: (1) perchloric acid homogenization and deproteinization of the tissue
      specimen and (2) conversion of purine nucleotides into parent drug or free bases
      by enzymatic or acid hydrolysis. The parent drug or purine bases formed were then
      analyzed on a Hypersil ODS column using isocratic elution with
      dihydrogenphosphate buffer for ganciclovir nucleotides or the gradient elution
      mode with dihydrogenphosphate buffermethanol for thiopurine nucleotides. The
      sample treatment procedure was evaluated using guanosine triphosphate (GTP), 6
      thioinosinic acid (6TIMP) and 6-thioguanosine monophosphate (6TGMP) as standards.
      Mean analytical recoveries determined by adding known concentrations of standards
      to the tissue specimen before sampling processing were higher than 97%. The
      sample preparation described is simple and represents a suitable method for the
      investigation of active nucleotide pool in tissues.

PMID- 9004941
TI  - Automated high-performance liquid chromatographic separation with
      spectrofluorometric detection of a malondialdehyde-thiobarbituric acid adduct in
      plasma.
AB  - An automated HPLC separation method for the detection of malondialdehyde (MDA) in
      plasma samples of a healthy population is described. The procedure involves a
      first step of acidic hydrolysis and complex formation with thiobarbituric acid
      (TBA), then a protein precipitation step, and finally the separation of TBA-MDA
      adducts through a complete HPLC apparatus with spectrofluorometric
      quantification. This procedure is very useful for a routine laboratory because of
      its rapidity (tR = 1.7 min), simplicity and applicability, and the method gives
      very good results with respect to linearity (0.1-12 mumol/l), precision (within
      assay C.V.%: 8, between-assay C.V.%: 10) and accuracy (recovery average: 91.66%).

PMID- 9004942
TI  - Simultaneous determination of L-702,007, a HIV-1 reverse transcriptase inhibitor,
      and its 6-hydroxy metabolite in human plasma by column-switching high-performance
      liquid chromatography with fluorescence detection.
AB  - A method for the determination of L-702,007, a human immunodeficiency virus type
      1 reverse transcriptase inhibitor, and its 6-hydroxy metabolite in human plasma
      is described. Plasma samples are extracted using phenyl solid-phase extraction
      columns. The extract is analyzed by HPLC using a column-switching system to
      remove interferences from late-eluting endogenous components. Fluorescence
      detection at an excitation wavelength of 314 nm and an emission wavelength of 390
      nm is utilized. The assay was validated in the concentration range of 10-200
      ng/ml when 1-ml aliquots of plasma were extracted. The assay has been used to
      support human pharmacokinetic studies.

PMID- 9004944
TI  - High-performance liquid chromatographic determination of penicillins by means of
      automated solid-phase extraction and photochemical degradation with
      electrochemical detection.
AB  - An automated precolumn exchange system for on-line solid-phase extraction (OPS-2)
      coupled to liquid chromatography with photochemical degradation and
      electrochemical detection was used for the determination of residual amounts of
      penicillin G, penicillin V, oxacillin, cloxacillin and dicloxacillin. A 5-10-fold
      increase in sensitivity was obtained when compared with direct UV detection of
      penicillins at 225 nm. The system is recommended for samples that have received
      an immunoaffinity clean-up. Analysis of bovine muscle tissue indicated, however,
      that this procedure could also be suitable for the determination of penicillin G
      at its maximum residue limit of 50 micrograms/kg even with conventional solvent
      partitioning for the first clean-up steps.

PMID- 9004943
TI  - Reversed-phase high-performance liquid chromatographic study of thimerosal
      stability in Cuban recombinant hepatitis B vaccine.
AB  - Non-degraded thimerosal was determined in the presence of its decomposition
      products by directly assaying recombinant hepatitis B vaccine using a reversed
      phase liquid chromatographic method. Methanol-water-orthophosphoric acid
      (65:35:0.9, v/v/v) was used as the eluent. Salicylic acid was employed as an
      internal standard. The calibration graph was linear (r = 0.99995) up to 2.5
      micrograms of thimerosal. Interference from aluminium hydroxide was eliminated by
      centrifugation. Good stability of thimerosal in the hepatitis B vaccine was
      demonstrated. The results obtained were in agreement with the recently proposed
      mechanism of degradation.

PMID- 9004945
TI  - Determination of FCE 26644, a new polysulphonated derivative of distamycin A, in
      monkey plasma by reversed-phase ion-pair high-performance liquid chromatography
      with ultraviolet detection.
AB  - A sensitive and selective ion-pair high-performance liquid chromatographic method
      for the determination of 7,7'-carbonylbis[imino-N-methyl-4, 2
      pyrrolecarbonylimino(N-methyl-4,2-pyrrole)carbonylimino]?- bis(1,3
      naphthalenedisulphonic acid), tetrasodium salt in monkey plasma has been
      developed. The compound and internal standard (bromphenol blue) were extracted
      from plasma samples were methylene chloride (twice) after deproteination with
      acetonitrile and addition of the ion-pairing agent (tetrabutylammonium
      hydroxide). The combined organic phases were dried, the residue dissolved in the
      mobile phase and then analysed by reversed-phase ion-pair liquid chromatography
      under isocratic conditions. The HPLC analysis time was about 20 min. Quantitation
      was achieved by UV detection at 323 nm. The linearity, precision and accuracy of
      the method were evaluated. The limit of quantitation was 0.3 microgram/ml plasma.
      No interference from blank monkey, mouse, rat, dog and human plasma was observed.
      The suitability of the method for in vivo samples was checked by analysis of
      plasma samples drawn from three male cynomolgus monkeys that had received a 20
      mg/kg single i.v. dose of the test compound.

PMID- 9004946
TI  - Improved determination of sulfadiazine in human plasma and urine by high
      performance liquid chromatography.
AB  - A high-performance liquid chromatographic method for the determination of
      sulfadiazine in human plasma and human urine was developed and validated. The
      method involves the acid extraction of drug and internal standard from plasma
      with ethyl acetate followed by evaporation and reconstitution in mobile phase.
      Urine samples were simply diluted with purified water. Recovery, linearity, intra
      and inter-day variation of sulfadiazine were tested and found appropriate. The
      quantitation range was 0.0299-15.2 micrograms/ml for plasma samples and 0.578
      148.8 micrograms/ml for urine samples. The method is suitable for the
      quantitation of sulfadiazine from pharmacokinetic studies.

PMID- 9004949
TI  - Determination of illicit drugs and related substances by high-performance liquid
      chromatography with an electrochemical coulometric-array detector.
AB  - A general method for the simultaneous determination of fifteen common drugs (6
      acetylmorphine, 3,4-methylenedioxymetamphetamine, buprenorphin, cocaine, codeine,
      dihydrocodeine, ethylmorphine, heroin, hydrocodone, lidocaine, methadone,
      morphine, naloxone, procaine and thebaine) was developed using reversed-phase
      HPLC and electrochemical detection. The separation of the drugs was achieved by
      using as the mobile phase 20 mM monobasic sodium phosphate-acetonitrile (90:10)
      with a gradient to 50% of the organic modifier, on a silica based C18 column (150
      x 4.6 mm I.D.) of 3 microns particle size and by the selectivity supplied by an
      array of eight coulometric electrodes at increasing potential. It was possible to
      identify and to determine fifteen different drugs in the same chromatographic run
      in 50 min. The method was tentatively applied to the determination of drugs in
      extracts of human hair.

PMID- 9004950
TI  - Determination of morphine, morphine-3-glucuronide and morphine-6-glucuronide in
      human serum by solid-phase extraction and liquid chromatography-mass spectrometry
      with electrospray ionisation.
AB  - A high-performance liquid chromatographic (HPLC) method for the simultaneous
      determination of morphine and two of its metabolites, morphine-3-glucuronide
      (M3G) and morphine-6-glucuronide (M6G), in serum is described. The compounds are
      extracted from serum using Sep-Pak light C18 solid-phase extraction cartridges,
      separated on an ODS C18 analytical column (100 x 4.6 mm I.D.) and detected by
      electrospray ionisation mass spectrometry. The separation was achieved by running
      a linear gradient from 4 to 70% acetonitrile with formic acid added as modifier.
      The flow-rate in the column was 1.0 ml/min. After the column, the eluate was
      subjected to a 1:50 split, with 20 microliters/min delivered to the mass
      spectrometer and 980 microliters/min delivered to waste. The compounds were
      detected in the mass spectrometer by selected-ion monitoring for m/z 286.2 for
      morphine and 462.2 for M3G and M6G. The spray voltage was 2.4 kV and the sampling
      cone was set at 40 V. The compounds have been quantified in serum over a
      concentration range of 2.9-60 nmol/l (0.84-17 ng/ml) for morphine, 11-1080 nmol/l
      (5.0-500 ng/ml) for M3G and 4.3-220 nmol/l (2.0-100 ng/ml) for M6G using external
      standardisation. Intra-assay and inter-assay precision were in the range of 2.4
      9.0% for all compounds. The major advantage with the present LC-MS method was the
      shorter analysis time, 10 min per sample compared to 45 min per sample with our
      previous LC method with dual detectors. The LC-MS method has proved to have both
      the selectivity and sensitivity needed for pharmacokinetic studies.

PMID- 9004948
TI  - Improved high-performance liquid chromatographic determination of amoxicillin in
      human plasma by means of column switching.
AB  - A highly sensitive and selective HPLC method was developed for the determination
      of amoxicillin in human plasma. After addition of buffer and internal standard,
      the sample was ultrafiltered and injected on to a precolumn to remove polar
      plasma interferences. Detection was effected with a UV detector set at 230 nm.
      The limit of quantification for amoxicillin was 50.1 ng/ml with an imprecision of
      4.2% using 0.25 ml of plasma. Linearity was confirmed over the whole calibration
      range (25.4-0.0501 micrograms/ml) and the inter-day variation ranged from 2.0 to
      4.5%. The method was validated according to GLP guidelines and its suitability
      was demonstrated by the analysis of several hundred samples in a bioequivalence
      study. The method can be used to determine pharmacokinetic parameters of
      amoxicillin in humans after a single oral dose of 500 mg.

PMID- 9004947
TI  - Sensitive determination of nitrofurantoin in human plasma and urine by high
      performance liquid chromatography.
AB  - A highly sensitive and selective HPLC method was developed and validated for the
      determination of nitrofurantoin in human plasma and urine. The method involves
      the liquid-liquid extraction of drug and internal standard from plasma with ethyl
      acetate followed by evaporation and reconstitution in mobile phase. Urine samples
      were simply diluted with purified water. UV detection was done at 370 nm. The
      limit of quantification for nitrofurantoin in plasma was 0.010 micrograms/ml. In
      urine nitrofurantoin could be quantified down to 0.380 microgram/ml. Linearity
      was proven over the whole calibration range in plasma (2.48-0.0100 microgram/ml)
      as well as in urine (187 micrograms/ml-0.380 microgram/ml). The method was
      validated according to Good Laboratory Practice guidelines and its suitability
      was demonstrated by analysis of samples from a pharmacokinetic study.

PMID- 9004951
TI  - Fluorimetric method of analysis for D-norpseudoephedrine hydrochloride, glycine
      and L-glutamic acid by reversed-phase high-performance liquid chromatography.
AB  - The determination of D-norpseudoephedrine HCl, an appetite suppressant, and
      glycine and L-glutamic acid, both dietary supplements, in pharmaceutical
      formulations and dissolution media using reversed-phase high-performance liquid
      chromatography (HPLC) combined with fluorimetric detection is reported. A reagent
      solution containing omicron-phthalaldehyde and a reducing agent, mercaptoethanol,
      appeared to be the most favourable reagent for derivatising the three compounds.
      The use of this HPLC method allowed for selective and quantitatively accurate
      analysis and was sufficiently specific, precise and sensitive for analytical
      characterisation.

PMID- 9004952
TI  - New sensitive method for the determination of hydrochlorothiazide in human serum
      by high-performance liquid chromatography with electrochemical detection.
AB  - A HPLC method with a very sensitive electrochemical detection has been developed
      for determining the diuretic agent hydrochlorothiazide (HCT) in serum of
      volunteers to whom a single dose of the fixed combination of 12.5 mg HCT and 25
      mg triamterene was administered. In the present method samples (0.2 ml serum, pH
      7) were purified by extraction of HCT into 5 ml tert.-butyl-methyl ether. The
      separated organic phase was spiked with p-aminobenzoic acid (PABA) standard. The
      separation was performed on a reversed-phase C18 column using phosphate buffer
      acetonitrile (90:10). A coulometric cell was used to measure HCT and an
      ultraviolet detector for PABA. The limit of quantitation for serum samples of
      only 200 microliters was 5 ng/ml (i.e. 60 pg HCT/injection) with a good
      reproducibility (1-8%). Short retention times were found: 1.2 min for PABA and
      5.8 min for HCT.

PMID- 9004953
TI  - High-performance liquid chromatographic assay for diltiazem in small-volume blood
      specimens and application to pharmacokinetic studies in rats.
AB  - A high-performance liquid chromatographic (HPLC) method was developed which
      involves the use of two 5-microns BDS silica gel columns (15 cm x 4.6 mm I.D.) in
      series for increased resolution and sensitivity, and an organic mobile phase for
      both extraction and elution of diltiazem. Plasma samples (400 microliters) were
      extracted using the organic mobile phase [n-hexane-methanol-dichloromethane
      ammonia (370:35:30:0.3)] and the extracts were monitored at 240 nm. Desipramine
      (30 micrograms ml-1) was the internal standard. The limit of quantification in
      plasma was 20 ng ml-1 with a correlation coefficient of > or = 0.999 within the
      20-800 ng ml-1 standard window. The inter- and intra-assay R.S.D.s were within
      5%. The recovery of diltiazem varied from 101.1% at 20 ng ml-1 to 93.7% at 400 ng
      ml-1. The method was applied to the investigation of diltiazem absorption in a
      rat. Drug absorption was based on the intestinal single-pass perfusion model. The
      concentration of diltiazem in all test perfusion solutions was 1 mg ml-1 (2.4 mM)
      and the flow-rate through the system was 3.33.10(-3) ml s-1. A non-specific
      mucolytic absorption enhancer was also added to a diltiazem solution and studied
      in the in situ system. The pharmacokinetics of diltiazem hydrochloride were
      investigated in two study groups of Wistar rats (n = 4). A two-sample Student's t
      test was employed to compare values of the area under the curve (AUC). The
      pharmacokinetic data indicated that the AUC in the group which received the
      enhancer [18.12 +/- 5.43 ng ml-1 h-1 (+/- S.D.)] was higher than that in the
      control group (11.49 +/- 3.67 ng h-1 ml-1), t-test; p = 0.0483. Hence it was
      shown that administration of an enhancer could increase the oral bioavailability
      of diltiazem.

PMID- 9004954
TI  - Determination of ethambutol in human plasma and urine by high-performance liquid
      chromatography with fluorescence detection.
AB  - A sensitive and selective HPLC method for the determination of ethambutol in
      human plasma and urine was developed. Ethambutol was extracted from basified
      plasma samples (0.2 ml) with diethyl ether, back-extracted into 0.01 M phosphoric
      acid and derivatized with 4-fluoro-7-nitrobenzo-2-oxa-1, 3-diazole. After 30 min
      at 80 degrees C and elimination of the reactive excess, the compound was
      determined by reversed-phase liquid chromatography. urine was analysed for
      ethambutol after dilution 1:200 with distilled water and derivatization as
      described for plasma. Quantification in plasma and urine was achieved by
      fluorescence detection of the eluate. The linearity, precision and accuracy of
      the method were evaluated. No interference from the constituents of human plasma
      and urine was observed. The limit of quantification was 10 ng/ml in plasma and 10
      micrograms/ml in urine. The suitability of the method for in vivo samples was
      checked by analysis of plasma and urine samples drawn from healthy volunteers who
      had received a 1200-mg oral dose of the test compound.

PMID- 9004955
TI  - High-performance liquid chromatographic determination of baclofen in human
      plasma.
AB  - A reversed-phase isocratic HPLC method is described for the determination of
      baclofen in human plasma. Solid-phase extraction using a SCX Bond Elut column is
      used followed by derivatization with o-phthalaldehyde-tert.-butanethiol and
      electrochemical detection. Both the within- and between-day R.S.D. and inaccuracy
      are less than 10% and 7%, respectively, even at the limit of quantification of
      the method, i.e., 10 ng/ml. The method was shown to give optimum performance in
      terms of sensitivity, precision and accuracy for the pharmacokinetic study of
      baclofen after a single oral administration to volunteers.

PMID- 9004956
TI  - Determination of the arotinoid mofarotene in human, rat and dog plasma by high
      performance liquid chromatography with automated column switching and ultraviolet
      detection.
AB  - A sensitive and specific high-performance liquid chromatographic method was
      developed and validated for the determination of the third-generation retinoid
      (arotinoid) mofarotene (Ro 40-8757) in human, rat and dog plasma, using direct
      injection of deproteinated plasma samples, automated column switching (on-line
      solid-phase extraction) and ultraviolet detection. Plasma (0.5 ml) was
      deproteinated by adding ethanol (1 ml) containing the internal standard Ro 42
      8659 (200 ng/ml). After centrifugation, 0.9 ml of the supernatant were directly
      injected onto a precolumn packed with C18 Corasil 37-50 microns. Polar plasma
      components were washed out from the precolumn using 1% ammonium acetate-acetic
      acid-acetonitrile (900:9:100, v/v/v). After valve switching, the pre-concentrated
      compounds were transferred to the analytical column (C18) in the backflush mode,
      separated by gradient elution and detected at 300 nm. The retention times (total
      run times) were approximately 15 and 20 min for the internal standard and
      mofarotene, respectively. The method was linear in the range 10-1000 ng/ml with a
      limit of quantification of 10 ng/ml. The mean recoveries were 80.4%, 81.7% and
      77.8% (range 10-1000 ng/ml) and the inter-assay precision was 2.7% (range 20-1000
      ng/ml), 1.5% and 2.0% (both range 100-1000 ng/ml) for human, rat and dog plasma,
      respectively. Mofarotene was found to be stable in human, rat and dog plasma
      stored at -20 degrees C for 3 months and 22 degrees C for 24 h. The method was
      successfully applied to clinical, pharmacokinetic and toxicokinetic studies.

PMID- 9004957
TI  - Stereoselective determination of unchanged and glucuroconjugated eliprodil, a new
      anti-ischaemic drug, in human plasma and urine by precolumn derivatization and
      column-switching high-performance liquid chromatography with fluorescence
      detection.
AB  - An HPLC method was developed and validated for the determination in human plasma
      and urine of the enantiomers of eliprodil, (+/-)-alpha-(4-chlorophenyl)-4[(4
      fluorophenyl) methyl]piperidine-1-ethanol hydrochloride, a new anti-ischaemic
      agent administered as a racemate. Both enantiomers are present in human plasma in
      unchanged and glucuroconjugated form, whereas only the glucuroconjugated form is
      excreted into urine; as a consequence, such metabolites in human plasma and urine
      should be submitted to enzymatic deconjugation with beta-glucuronidase
      (Escherichia coli) before being extracted. The general method involves a liquid
      liquid extraction of eliprodil and internal standard from alkalinized plasma or
      urine with n-hexane, evaporation of the organic phase and derivatization with (S)
      (+)-naphthylethyl isocyanate to give carbamate diastereoisomeric derivatives of
      (S)-(+)- and (R)-(-)-eliprodil and internal standard; after evaporation of the
      derivatizing mixture and dissolution of the residue in a small volume of
      phosphate buffer-acetonitrile (60:40, v/v), an aliquot is injected into a column
      switching HPLC system. The derivatized sample extract is purified on a precolumn
      filled with C8-bonded silica material, which is flushed with acetonitrile-water,
      then diastereoisomers of eliprodil and the internal standard are automatically
      transferred by the mobile phase to the analytical column. The analytical column
      is a C8 type, specially deactivated for basic compounds, the mobile phase is
      0.025 M phosphate buffer (pH 2.6)-methanol-acetonitrile (42:2:56) at a flow-rate
      of 1.2 ml min-1 and fluorimetric detector operating at lambda ex = 275 nm and
      lambda em = 336 nm is used. The retention times, under these conditions, are
      about 16 and 17 min for (S)-(+)- and (R)-(-)-eliprodil diastereoisomers,
      respectively, and about 19 min for the first-eluted diastereoisomer of the
      internal standard. During the analysis time, the precolumn, reset in a different
      path from that of the analytical column, is back-flushed with different solvents,
      then re-equilibrated with acetonitrile-water before the next injection. Linearity
      in plasma, for unchanged eliprodil enantiomers, was assessed in the range 0.15-10
      ng ml-1 and for total eliprodil enantiomers (unchanged + conjugated) in the range
      0.75-500 ng ml-1; the limit of quantitation (LOQ) is 0.15 ng ml-1 for each
      unchanged enantiomer and 0.75 ng ml-1 for each total enantiomer. Linearity was
      also assessed in urine for total (conjugated) eliprodil enantiomers in the range
      50-25 000 ng ml-1; the LOQ is 50 ng ml-1 for each enantiomer. The intra- and
      inter-day precision and accuracy of the method were investigated in plasma and
      urine and found to be satisfactory for pharmacokinetic studies. The method has
      been extensively used in pharamcokinetic studies in man treated with a 20-mg dose
      of eliprodil racemate and some results of this application are reported.

PMID- 9004958
TI  - Determination of captopril and its disulphides in whole human blood and urine by
      high-performance liquid chromatography with ultraviolet detection and precolumn
      derivatization.
AB  - An assay that measures the total, and protein-bound captopril, the orally active
      antihypertensive drug, in whole human blood and urine has been developed. The
      procedure involves a precolumn derivatization of the drug via its sulfhydryl
      group with 1-benzyl-2-chloropyridinium bromide followed by solid-phase extraction
      and reversed-phase high-performance liquid chromatography separation with
      ultraviolet detection at 314 nm. Oxidized and protein-bound captopril is
      converted to reduced form by the use of triphenylphosphine and derivatized and
      quantified in the same manner. The proposed method offers the possibility of
      determining the in vivo redox status of captopril in blood of patients orally
      given a standard dose of at least 12.5 mg of captopril as part of the treatment
      of hypertensive disease and/or congestive heart failure. In the recommended
      procedure the sulfhydryl form of captopril is trapped with minimal oxidation by
      derivatizing blood samples at the time of collection. This is attained by drawing
      blood directly into tubes containing solutions of 1-benzyl-2-chloropyridinium
      bromide. The method enables also the determination of urinary excretion of
      captopril and its disulphides after oral administration of the drug. Accurate
      determinations are possible over a concentration range of 10 to 500 ng/ml
      captopril in blood, 50 to 1200 ng/ml captopril in urine and 10 to 1000 ng/ml
      captopril disulphide and 50 to 3000 ng/ml captopril disulphide in blood and
      urine, respectively. The detection and quantification limits for both blood and
      urine are 0.3 and 10 ng/ml, respectively.

PMID- 9004960
TI  - Application of high-performance liquid chromatography with diode-array detection
      and on-line post-column photochemical derivatization to the determination of
      analgesics.
AB  - HPLC analyses of pharmaceutical dosage forms containing analgesics and related
      compounds (acetylsalicyclic acid, paracetamol, propyphenazone, caffeine and
      chlorpheniramine) were performed on C18 and cyano columns under reversed-phase
      conditions. The performance of the methods was enhanced by introducing postcolumn
      on-line photochemical derivatization in combination with a diode-array detection.
      The column effluents were subjected on-line to UV irradiation (254 nm) and the
      characteristic photo-induced spectral modifications were useful for the
      unambiguous identification of the various analgesic compounds. The proposed HPLC
      methods were successfully applied to the analysis of commercially available
      analgesic dosage forms.

PMID- 9004959
TI  - Location of the hydroxyl functions in hydroxylated metabolites of nebivolol in
      different animal species and human subjects as determined by on-line high
      performance liquid chromatography-diode-array detection.
AB  - Nebivolol hydrochloride (R067555), is a new antihypertensive drug. Aromatic and
      alicyclic hydroxylation at the benzopyran ring systems of nebivolol are important
      metabolic pathways. Generally, NMR is used to unambiguously assign the sites of
      hydroxylation. Because of the low dose rates and the extensive metabolism of
      nebivolol in the different species, NMR identification is not always possible,
      and therefore another spectroscopic technique was searched for to address this
      problem. UV-chromophore absorption is affected by the kind and arrangement of
      adjacent atoms and groups (auxochromes). The effect of these auxochromes (e.g. 
      NH2, -NR2, -SH, -OH, -OR and halogens) can be strongly influenced by the pH. This
      paper proves that HPLC at high pH combined with on-line diode-array detection is
      an excellent technique for the location of the hydroxyl functions in hydroxylated
      metabolites of nebivolol. With this technique it is possible to differentiate
      between glucuronidation at the automatic and aliphatic or alicyclic hydroxyl
      functions.

PMID- 9004961
TI  - High-performance liquid chromatographic evaluation of biogenic amines in foods.
      An analysis of different methods of sample preparation in relation to food
      characteristics.
AB  - Biogenic amines are compounds formed by amino acid decarboxylation in fermented
      foods. Most of the methods for amine determination involve acid extraction
      followed by a liquid-liquid purification step. The different parameters which can
      influence amine recoveries are considered; experience with different foods such
      as cheese, fish and meat preserves are reported and for each of them the
      optimized analytical procedure is described. Data concerning recovery and
      repeatability of the method are also reported and the various factors that
      influence amine extraction are discussed. The possibility of applying direct
      derivatization without any other purification step is also considered.

PMID- 9004962
TI  - Fluorimetric determination of diarrhetic shellfish toxins in scallops and mussels
      by high-performance liquid chromatography.
AB  - The fluorimetric determination of okadaic acid (OA) and dinophysistoxin-1 (DTX
      1), the principal toxins of diarrhetic poisoning, is reported. The digestive
      glands of mussels or scallops were homogenized with 2-propanol. OA and DTX-1 were
      extracted from the homogenate, with hexane-ethyl acetate and labelled with 2,3
      (anthracenedicarboximido)ethyl trifluoromethanesulfonate in dry acetonitrile.
      After cleaning up by passage through a short silica gel column, the fluorescent
      derivatives were determined by HPLC. The derivatives were at first separated on a
      Develosil Ph-5 column, and only the target fraction obtained was introduced into
      a Develosil ODS K-5 column by a valve-switching device. Both toxins were
      determined in the range 2.5-500 pg, and the detection limits were 0.8 pg (OA) and
      1.3 pg (DTX-1) with a signal-to-noise ratio of 3.

PMID- 9004963
TI  - Automatic high-performance liquid chromatographic method for the determination of
      diarrhetic shellfish poison.
AB  - A rapid HPLC method with fluorescence detection for the determination of okadaic
      acid (OA) and dinophysistoxin-1 (DTX-1) in mussels and mussel products is
      presented. For fluorescence labelling of OA and DTX-1, 9-anthryldiazomethane
      (ADAM) is used. HPLC with a column-switching system is proposed to avoid time
      consuming clean-up procedures after derivatization of sample extracts with ADAM.
      The column-switching system as well as the chromatographic conditions and
      detection are described.

PMID- 9004964
TI  - Influence of temperature on the retention behaviour of proteins in cation
      exchange chromatography.
AB  - The chromatographic behaviour of several amino acid derivatives, peptides and
      proteins has been investigated with the so called "tentacle-type" LiChrospher-100
      SO3- adsorbent and an analogous poly(2-sulphoethylaspartamide) cation-exchange
      adsorbent, PolySulphoethyl A. In particular, the dependences of the retention
      properties of a range of biosolutes on temperature and the chromatographic
      residence time were evaluated with the objective of gaining further insight into
      the influence of ligand type and flexibility and the role of solute conformation
      on the chromatographic behaviour of proteins with these two strong cation
      exchange chromatographic adsorbents. The results indicate that significant
      differences in the chromatographic retention behavior between proteins and low
      molecular-mass solutes occur as a function of temperature and the type of co- and
      counter ions present in the mobile phase with both adsorbents. Moreover, the
      dependences of the Zc and log Kc values on temperature for most of the proteins
      examined exhibited significant changes in magnitude between 4 and 75 degrees C,
      whilst no equivalent changes were evident for low-molecular-mass solutes. With
      the "tentacle-type" LiChrospher-1000 SO3- adsorbent at higher temperatures, e.g.,
      at 75 degrees C, most of the proteins could still be eluted although several
      exhibited very large increases in their retention parameters. With the
      PolySulphoethyl A adsorbent, on the other hand, none of the proteins examined
      were eluted at 75 degrees C. The results moreover indicate that hydrophobic
      interactions play an increasingly important role in protein retention with both
      types of ion-exchange adsorbents at higher temperatures, but are more dominant
      with the PolySulphoethyl A ligand. In general, the Zc values for the proteins
      with the "tentacle-type" LiChrospher-1000 SO3- adsorbent were greater than those
      obtained with the PolySulphoethyl A adsorbent, suggesting that the "tentacular"
      ligands present on this strong cation-exchange adsorbent interact with protein
      molecules through larger contact areas. Collectively, these investigations
      provide further support for the concept that the adsorption behaviour of proteins
      with the "tentacle-type" LiChrospher-1000 SO3- adsorbent and similar types of
      "tentacular" ligand systems involves a multilayer dissolution mechanism with the
      protein interacting with a more diffuse or extended Donnan double layer in the
      ion-exchange environment, resulting in multi-site binding processes.

PMID- 9004965
TI  - Preparative membrane adsorber chromatography for the isolation of cow milk
      components.
AB  - Preparative membrane adsorber (MA) chromatography was used to process milk
      fractions such as the whey and the permeate commonly obtained during lactose
      production in modern dairies. In MA systems the fluid-dynamic and mass-transfer
      properties are superior to conventional HPLC or fast protein liquid
      chromatography (FPLC) columns. Since the flow resistance caused by the MA stacks
      is quite low, high throughputs can be realized without loss in resolution. Feed
      sizes were varied from the laboratory scale (several ml) up to batches of 10 1
      during the investigations. MAs based on modified cellulose filtration membranes
      (average single layer thickness 200 microns, average pore size 5.0 microns) were
      used for the small-scale experiments. The MAs are functionalized by covalent
      linkage of strong and weak ion exchanger groups to their surface. Three
      commercially available types were used [strong ion exchanger: MA Q15 (3 layers of
      5 cm2) and MA Q100 (5 layers of 20 cm2); weak ion exchanger: MA D15 (3 layers of
      5 cm2); all Sartorious, Germany]. For the large-scale work a dead-end filtration
      unit containing up to 1300 cm2 of MA-area was used. Here MAs based on a synthetic
      co-polymer, that were prepared from cut-out sheets, were inserted.
      Chromatographic conditions were transferable from the cellulose- to the polymer
      based MA carrying the same functional groups. The influence of the flow-rate and
      the pH of the mobile phase on the separation was investigated. The flow-rate
      could be raised to the limit of the respective chromatographic systems and/or MA
      modules without loss in resolution. The use of the strong anion exchanger MA
      together with a mobile phase pH of 6.0 and a fine-tuned gradient allowed the
      separation of BSA, alpha-lactalbumin and the genetic variants of beta
      lactoglobulin, even though no baseline separation was possible in the latter
      case. The use of coupled modules rather than a single one is shown to improve the
      separation considerably.

PMID- 9004966
TI  - Perfusion liquid chromatography of whey proteins.
AB  - A perfusion reversed-phase (RP) HPLC method was developed for the rapid
      separation of the main bovine whey proteins: alpha-lactalbumin (alpha-LA), serum
      albumin (BSA) and the genetic variants of beta-lactoglobulin (A and B) (beta-LG A
      and beta-LG B). For the method development, the influence of factors favouring
      structural changes of proteins (temperature and organic acid concentration in the
      mobile phase), gradient and other chromatographic conditions and the mass of
      protein injected was examined. The optimized method allowed the separation of
      proteins in about 1.5 min (cycle time 3.5 min) with resolution around 1.0 for the
      beta-lactoglobulins. The method was applied to the determination of proteins in a
      whey from raw bovine milk. The precision of the determinations was < or = 3.75 mg
      per 100 ml (S.D.). With respect to the accuracy, errors < or = 7.0% in the
      determination of alpha-LA, beta-LG A and beta-LG B were obtained, compared with
      an RP-HPLC reference method. However, higher errors in the quantification of BSA
      were found owing to the lack of purity of the peak assigned. In addition, the
      proposed method has proved to be very useful in the detection of homologous whey
      proteins from different species (cow, sheep and goat) in milk mixtures.

PMID- 9004968
TI  - [Proposals for a strategy for evaluation and utilization of screening tests for
      hepatitis C].
AB  - New assays for the screening of anti-HCV antibodies are regularly proposed for
      registration. The evaluation of new tests is based on the measurement of their
      intrinsic value: sensitivity and specificity. To assess the sensitivity of a
      test, it is very important to be able to obtain sera samplets tested with a "Gold
      Standard", which is, for HCV, RNA detection. Sensitivity is defined as the ratio
      of the number of true positive to the number of true positive added to the number
      of false negative samples. The problem is to define the samples to be tested. It
      is methodologically impossible to use a serological test for samples selection.
      The Gold Standard might be performed on samples from the general population or
      more easily from risk groups. The estimation of the precocity is more difficult.
      The constitution of an acute hepatitis panel is of interest an the follow up of
      risk groups has to be encouraged. The estimation of the number of samples needed
      depends on the required precision in the sensitivity measurement. The confidence
      interval (CI) decreases when the number of samples tested increases and when the
      sensitivity is high. The important questions are opposite: if the test is
      positive what is the probability for the patient to be really positive? (positive
      predictive value PPV), and, if the test is negative, what is the probability for
      the patient to be non-infected? (negative predictive value: NPV). The NPV depends
      on the prevalence of HCV infection in the tested population and on the
      sensitivity of the test. PPV increases with the prevalence rate and the
      specificity. Regarding these results, one may suggest that donor screening assays
      and tests used for diagnose HCV infection in patients may be evaluated with
      different strategies. Regarding blood donors screening, sensitivity is the most
      important parameter, the best strategy is to eliminate risk groups, and then, to
      perform very sensitive assays on negative samples. On the other hand, for
      patients diagnosis, specificity (avoid false positive results) is more important.
      The best strategy is to select patients at risk from clinical findings and then,
      to perform a specific test. Screening strategies for the general population have
      to take into account these two different strategies.

PMID- 9004969
TI  - [Apheresis tolerance and acceptability in the child weighing 30 kg or less, with
      the exception of infants].
AB  - Over the ten past years, we performed 336 apheresis among 51 children who were 19
      months to 15 years old (10 to 30 kg body weight). 3 types of apheresis were
      carried out. 14 red blood cell exchange, 293 plasma exchanges and 29 peripheral
      blood stem cell collections (CSP). 5 different types of continuous or
      discontinuous flow machines have been used. Technical adaptations depending on
      patient blood volume, hematocrit, type of machine used and apheresis performed
      permitted us to obtain a very good tolerance and acceptability. According us, the
      apheresis should be used each time this treatment is needed in the child, because
      of the very low frequency of side effects.

PMID- 9004970
TI  - [Improvement of transfusion safety in a health care service through the
      implementation of a quality program].
AB  - The quality policy brings with it an efficient method as well as relevant tools
      to improve transfusion safety in health care services. This article illustrates
      the details of the approach through the presentation of a project developed in
      the East Picardie region throughout several hospitals. It underlines the
      importance of the choice of a good reference system, of a pertinent method and
      the necessity of a real project management. Furthermore, the follow-up of the
      project has enabled us to identify a certain number of success criteria in the
      steering of the changing process.

PMID- 9004967
TI  - [DNA polymorphism and paternity exclusions: analysis of 543 cases of paternity
      testing].
AB  - The study of the genetic markers of polymorphism has known a very large evolution
      during these last ten years in relation to the development of the molecular
      biology and the discovery and analysis of some DNA repeated loci. In a study of
      543 of paternity testing, the authors analyse the performance of some probes, the
      limits of their using, the program and strategy of testing to establish a high
      probability of exclusion.

PMID- 9004972
TI  - [Comparative prospective study of laparoscopic hysterectomy and abdominal
      hysterectomy].
AB  - Based on assembled findings, the authors assume that laparoscopically assisted
      vaginal hysterectomy is a real alternative of abdominal hysterectomy and extends
      the spectrum of indications to overcome contraindications of the vaginal approach
      in the treatment of benign diseases of organs of the lesser pelvis. In the
      investigated group of patients the advantages of the minimally invasive approach
      when evaluating convalescence parameters were confirmed. Introduction of LH had
      also a favourable impact on the interest in and extension of vaginal operations.
      It is essential to implement extensive prospective investigations which will
      evaluate objectively the contribution of endoscopic surgery and their effect on
      somatic, psychic, social and economic parameters.

PMID- 9004973
TI  - [Personal experience with laparoscopic hysterectomy].
AB  - The authors report their experience with 132 patients operated in the Boskovice
      hospital in the last two years. Their method-supracervical laparoscopic
      hysterectomy with removal of the cervical transformation zone and endocervix. All
      procedures were successfully completed laparoscopically. The authors analysed
      their cases according to the intraoperative, immediate postoperative and late
      postoperative complications. Average operating time is compatible with that of
      conventional total abdominal or vaginal hysterectomy and LAVH. The authors
      evaluated blood loss, hospital stay, recovery time, pain and cosmetic
      considerations. This method may be sufficient for cervical and endometrial cancer
      prophylaxis, because of thorough histologic examination and interpretation of
      morcellated cervical-cylinders and uterine body tissue.

PMID- 9004974
TI  - [Risk of fluid overload syndrome during hysteroscopy procedures].
AB  - At present increasingly liquid media are preferred to gaseous ones in
      hysteroscopic procedures. In operations the former media are used almost
      exclusively. The use of liquid media involves, however, some risks, the greatest
      one being the so-called fluid overload syndrome. It develops as a result of
      overload and upset of the milieu interior due to excessive escape of the
      distension medium. Medium escapes also via the oviducts into the peritoneal
      cavity. It is therefore necessary to adhere to safety measures which include in
      particular selection of a suitable medium, the time factor, correct surgical
      procedure and specially continuous control of consumption of the medium.

PMID- 9004975
TI  - [Estradiol valerate/cyproterone acetate in the treatment of climacteric
      syndrome].
AB  - In a prospective study 40 perimenopausal women with climacteric complaints
      between 45 to 52 years of age were examined. Twenty three (100%) were assigned to
      treatment with hormonal replacement therapy (Climen fy Schering-estradiol
      valerate cyproteron acetate) for 6 months. The therapy had to be stopped in 5
      women (22%) for side effects. The drug was contraindicated in 17 patients because
      of non-treated hypertension, varices, hepatopathy and uterine fibroids with
      repeated metrorrhagia. In 18 patients (78%) Climax score, ALT, AST, bilirubin,
      total cholesterol, HDL-Chol, LDL-Chol, triglycerides, haemogram, fibrinogen,
      APTT, Quick test, serum Ca2+ and P2+ and urine C2+ and P2+/24 hours, weight and
      arterial blood pressure before and after the treatment were examined. The results
      confirm the benefical effect of Climen on the Climax score (p < 0.0001), total
      cholesterol (p < 0.01), HDL-Chol (p < 0.05) and LDL-Chol (p < 0.0001). After
      administration of Climen a significant decrease of P2+ serum concentration was
      demonstrated. Climen is suitable for treatment of acute climacteric complaints
      and has benefical effects on lipid metabolism.

PMID- 9004971
TI  - Functional reach and single leg stance in patients with peripheral vestibular
      disorders.
AB  - The purpose of this study was to compare functional reach distance and right
      single leg stance time in patients who had peripheral vestibular disease. Twenty
      eight patients (15 female, 13 male) between the ages of 35 and 84 were asked to
      perform 3 trials each of functional reach (FR) and right single leg stance (SLS).
      SLS times were measured by a Kistler static force platform on line with a Caspar
      personal computer. FR distance was measured by using a free-standing 147-cm rule.
      In addition, each subject filled out the Dizziness Handicap Inventory (DHI).
      Trials were randomized to prevent fatigue or practice effects. A Pearson product
      moment correlation was performed between FR and SLS (r = 0.59, P = 0.001). Post
      hoc analyses of the first, the best, and the average scores highlighted the
      importance of using means for comparison in a population as variable as the
      vestibularly impaired. Post hoc analyses showed no correlation between the DHI
      score and either functional reach distance or single leg stance time. However,
      when the subjects were divided into groups based on DHI score (group 1 with DHI <
      or = 49/100, group 2 with DHI > or = 50/100) and a pooled two-sample t-test was
      performed, a significant difference (P = 0.05) was found in functional reach
      distance; the subjects who reported less perception of handicap reached farther
      than those who reported more perception of handicap. No difference was found
      between the two DHI groups in single leg stance time. Post hoc correlations of
      functional reach and single leg stance time. Post hoc correlations of functional
      reach and single leg stance within the two DHI groups showed a higher correlation
      in group 1 (DHI < or = 49/100), with r equals 0.65 (P < or = 0.01), than in group
      2 (DHI > or = 50/100), with r equals 0.38 (P = 0.20). The study found a highly
      significant, moderate correlation between functional reach distance and single
      leg stance times in patients with peripheral vestibular disease. These results
      support the use of FR as an additional assessment tool with patients who have
      peripheral vestibular disease.

PMID- 9004977
TI  - [Is involvement of the clitoris in epidermoid carcinoma of the vulva an adverse
      prognostic sign?].
AB  - Retrospective evaluation of 360 patients with vulvar cancer during the period
      from 1975 to 1994. From this group in 215 patients radical vulvectomy with
      bilateral inguinal lymph node extirpation was performed. After excluding 35
      patients in the IVth stage of the disease, 11 with vulvar melanoma and 9 who did
      not attend in the group of the remaining 160 cases 3- 5- and 10-year survival
      rates were evaluated. Forty of the cancers clitoris of these 160 cases do not
      confirm that this localisation is a bad prognostic factor.

PMID- 9004976
TI  - [Erythrocyte zinc-protoporphyrin and characteristics of iron- deficiency anemia
      in parturient women and neonates].
AB  - The authors examined the concentration of erythrocyte zinc-protoporphyrin (ZPP)
      by a haematofluorometric method in 175 women during delivery and the levels in
      their children. They assessed basic haematological indicators, the number of red
      cells, their volume, number of reticulocytes, haemoglobin concentration,
      haematocrit and sideraemia. All were average values within the physiological
      range in both examined groups. Statistical evaluation revealed a significant
      difference between mean values of sideraemia in mothers and children and mean
      values of the erythrocyte ZPP in both groups. The authors found also a medium
      significant correlation between ZPP and the erythrocyte volume and the
      erythrocyte volume and sideraemia. The correlation of different indicators was
      more marked after classification of the examined women and neonates into
      subgroups by haemoglobin concentrations and ZPP. In the subgroup of mothers with
      Hb values lower than 115 g/l a positive correlation was found with the number of
      reticulocytes red cell volume and sideraemia. In the subgroup of anaemic women
      (Hb concentration lower than 105 g/l) a negative correlation with the foetal
      sideraemia was found.

PMID- 9004978
TI  - [The first pregnancy in the Czech Republic achieved with a combination of MESA
      ICSI: preliminary report].

PMID- 9004979
TI  - [Management of premature labor before the 28th week of pregnancy].

PMID- 9004980
TI  - [Reproductive medicine and assisted reproduction--present status and perspectives
      in the Czech Republic].

PMID- 9004981
TI  - [Autoimmune habitual abortion].

PMID- 9004983
TI  - Psychiatric genetics.

PMID- 9004982
TI  - Long-term stability of diagnosis and symptom dimensions in a systematic sample of
      patients with onset of schizophrenia in childhood and early adolescence. II:
      Postnegative distinction and childhood predictors of adult outcome.
AB  - BACKGROUND: The aim of this study was to verify the presence and stability across
      life of the positive/negative distinction in early-onset schizophrenia (EO-SZ)
      through a longitudinal factor analysis of the schizophrenic dimensions, and to
      identify the factors predicting several indices of long-term outcome for EO-SZ.
      METHOD: Forty children consecutively referred for DSM-III-R schizophrenia (SZ) in
      a specific catchment area comprised the sample. RESULTS: Across a 14.8-year
      follow-up, longitudinal factor analysis identified two separate factors
      corresponding to the positive and negative symptom dimensions. We also observed
      that: the GAS rated over the last three years of adult illness and the severity
      of negative symptoms during the stabilised interepisode intervals in adulthood
      were the indices of adult outcome that were most easily predicted; and the best
      childhood predictors of adult outcome were premorbid functioning and severity of
      positive and negative symptoms during acute episodes. CONCLUSIONS: The presence
      of premorbid non-psychotic behaviour disturbances (NPBD) and premorbid
      developmental problems was not related to severity of outcome, in contrast to the
      former variables.

PMID- 9004984
TI  - [Main principles of training physicians in clinical laboratory diagnosis].

PMID- 9004985
TI  - [Methods of determination of phenol and its derivatives in biological media
      (literature review)].

PMID- 9004987
TI  - [Serotonin concentration in the blood of patients with hemorrhagic fever with
      renal syndrome].
AB  - Differences in the concentrations of serotonin in whole blood and plasma of
      patients with hemorrhagic fever with the renal syndrome prompted measurements of
      serotonin in different components of the blood. The concentration of serotonin in
      whole blood was found to depend on its hemoconcentration: the higher is the
      hematocrit, the greater is the difference between serotonin content in the plasma
      and whole blood. In case of hemoconcentration or hemodilution it is impossible to
      assess serotoninemia from the level of serotonin in whole blood.

PMID- 9004988
TI  - [Experience in the determination of iodine in the urine by the kinetic cerium
      arsenite method].
AB  - The authors describe the kinetic cerium arsenite method for measuring iodine in
      the urine using reagents made in Russia. The urine is prepared for analysis by
      wet calcination with a mixture of chlorous and perchloric acids. The method of
      synthesizing chlorous acid, preparing reagents, collecting urine, and procedure
      of analysis are described. The method was used for assessing iodine excretion
      with the urine in schoolchildren of Novosibirsk and Kemerovo.

PMID- 9004989
TI  - [Determination of acetylation phenotype in the therapeutic monitoring of drugs].
AB  - New methods for detecting the acetylation phenotype have been developed for
      therapeutic monitoring using isoniazid as the pharmacogenetic marker. The study
      is carried out with 4-chloro-5,7-dinitrobenzofurane by direct spectrophotometry,
      high performance liquid and thin-layer chromatography. The methods proved to be
      highly sensitive, selectively detecting isoniazid, simple, and requiring no
      sophisticated equipment. The methods were tried in examinations of patients with
      visceral diseases. Effects of various inductors on the acetylation rate were
      assessed.

PMID- 9004986
TI  - [Diagnostic significance of beta 2-microglobulin after allotransplantation of
      cultured pancreatic islet cells of human fetus].
AB  - Twenty-nine patients with type I diabetes mellitus were followed up for at least
      a year after intramuscular allotransplantation of cultured fetal pancreatic islet
      cells. The patients were divided into 2 groups with different types of
      proteinuria. Group 1 (prenephritic stage) consisted of 16 patients with
      transitory proteinuria and group 2 (nephritic stage)-of 13 with constant
      proteinuria. Serum beta 2-microglobulin (beta 2 mg) was radioimmunoassayed before
      transplantation and 7 weeks, 1, 3 to 6 months, and over a year after it. The
      levels of beta 2 mg appreciably varied in the two groups. In group 2 they were
      increased on day 7 but later virtually did not differ from the control. In group
      1 one patient developed a decreased beta 2 mg level starting from the first up to
      the sixth months after allotransplantation. The results indicate that diabetic
      nephropathy may be partially reversed by allotransplantation and hence, this
      method is recommended for patients with transitory proteinuria.

PMID- 9004990
TI  - [Use of chemiluminescent analysis of the blood in prognostication of the course
      of adaptation period of the newborn].
AB  - Study of spontaneous and hydrogen peroxide-induced chemiluminescence of the blood
      serum of children born clinically healthy to mothers with complicated course of
      pregnancy showed that an increase of the total photosum of spontaneous
      chemiluminescence on day 3 of life may be regarded as a criterion of failure of
      adaptation; other criteria are the photosum value and intensity of the amplitude
      of flashes of induced chemiluminescence of newborn blood sera over the entire
      course of the neonatal period.

PMID- 9004991
TI  - [Use of microtest systems for identification of newly isolated clinical strains].
AB  - Species appurtenance of 425 clinical strains isolated from various types of
      material from December 1993 to November 1994 was identified using Lachema
      (Czechia) Micro-la-test. There were 99 staphylococcal, 139 streptococcal, 119
      enterobacterial cultures, and 68 nonfermenting gram-negative bacteria. The
      microorganisms were characterized completely according to their code in 67.7%
      cases (STAPHYtest), 54% (STREPTOtest), 25.2% (ENTEROtest), and 22.1%
      (NEFERMtest). False-positive reactions in the control were detected in 22.2%
      (STAPHYtest), 33.3% (STREPTOtest), 11.8% (ENTEROtest), and 41.7% (NEFERMtest) of
      the number of biochemical characteristics in a plaque. Unclear reactions (+/-)
      making identification difficult were observed in 100% cases for STAPHYtest, 83.3%
      for STREPTOtest, 91.7% for ENTEROtest-1, and 58.3% for NEFERMtest. Atypical
      reactions, not corresponding to the studied species, were observed in 62.5% cases
      with STAPHYtest, 41.7% with STREPTOtest, 66.7% with ENTEROtest-1, and 58.3% with
      NEFERMtest. Still, STREPTOtest with the probability of verifying 61.5 to 87.5% of
      the cultures may be used for identifying the species appurtenance of alpha
      hemolytic streptococci.

PMID- 9004994
TI  - [Clinical value of laboratory investigations].

PMID- 9004992
TI  - [A comparative study of the effectiveness of commercial microtest systems for
      identification of microorganisms of different groups in clinical microbiology].
AB  - Studies of 806 strains of cultures isolated from pathological material
      demonstrated the possibility of using microtest systems MMTE1 and 2 (ALLERGEN
      Research and Production Plant in the town of Stavropol) and ENTEROtest 1 and 2
      and ENTEROtest 16 for identification of enterobacteria and NEFERMtest,
      STAPHYtest, STREPTOtest, and ANAEROtest for the identification of respective
      groups of microorganisms at practical microbiological laboratories (Lachema,
      Czechia). The microtest kits are easy to use and fit for mass screenings; they
      permit simultaneous testing in 9 to 23 biochemical tests. Use of these test kits
      allows species identification of 63.3 to 80.7% cultures making use of biochemical
      activity tables and indexes recommended in instructions for the use of microtest
      kits and 85.6 to 96.1% cultures making use of IDENT computer software.
      Introduction of microtest kits in the practical activity of microbiological
      laboratories will appreciably improve the quality of microbiological
      investigations and allow the use of automated microbiological systems.

PMID- 9004993
TI  - [Diagnosis of urogenital chlamydiosis using rapid immunoenzyme method: Abbott
      TestPack Chlamydia].
AB  - Twenty women suffering from chronic genital inflammations were screened for
      urogenital chlamydiosis using Abbott Testpack Chlamydia kit for enzyme
      immunoassay (EIA) and NIARmedik Chlamoscan kit for immunofluorescent method. The
      cells were scraped off from the cervical canal during the second phase of the
      cycle. In addition, smears were taken from the vagina and cervical canal to be
      screened for microflora using Romanowsky-Giemsa staining. EIA detected C.
      trachomatis antigens in 3 (15%) out of 20 examinees, whereas direct
      immunofluorescence revealed these antigens in only 2 (10%) patients. The results
      differed in a patient with urogenital candidiasis. Evidently, the system of
      special filters in the Testpack Chlamydia releases the cell suspension from
      concomitant cell dendrites, blood, mucus, and thus increases the sensitivity of
      the test.

PMID- 9004995
TI  - [Modified method of inoculation of hemocultures from patients with suppurative
      septic diseases and typhoid-paratyphoid fever].
AB  - A modified method of isolating hemocultures in pyoseptic processes is proposed.
      It consists in combined use of two known methods: inoculation of the blood by in
      depth method and preliminary hemolysis of the blood, and use of commercial medium
      for assessing the sterility as the nutrient base. High efficacy of the proposed
      method has been demonstrated in experiments with 17 reference strains of
      microorganisms. The new approach helped improve the isolation rate of
      opportunistic enterobacteria, nonfermenting gram-negative bacteria,
      staphylococci, highly demanding streptococci, and other microorganisms similar in
      nutrient requirements, as well as the agents of typhoid and paratyphoid fever.
      This permits unifying the methods of investigation of hemocultures in pyoseptic
      diseases and typhoid-paratyphoid fevers'.

PMID- 9004996
TI  - [Methods of intraspecies differentiation of Enterobacter cloacae by biochemical
      reactions].
AB  - Three methods of intraspecies differentiation of Enterobacter cloacae by
      biochemical tests were compared on 14 clinical strains of different origin and 1
      reference strain of this enterobacterium. The methods employed were the original
      and modified Old's method of biotyping and a method for assessing the biochemical
      profile of E. cloacae strains using bioMerieux API 20E system (France). Modified
      Old's method was found to be the most convenient for practical studies.

PMID- 9004997
TI  - [The reply of Professor V.V. Dolgov, Head of the Laboratory Service of the
      Russian Federation Ministry of Health, to A.A. Artemenkov].

PMID- 9005000
TI  - Genocide in Rwanda.

PMID- 9004998
TI  - [Proposed guidelines. Strategy for improving rational use of laboratory tests.
      International Federation of Clinical Chemistry (IFCC)].

PMID- 9004999
TI  - [Russian Scientific Society of Clinical Laboratory Diagnosis].

PMID- 9005001
TI  - [Patients with asthma of difficult control].

PMID- 9005002
TI  - [Inhalation therapy in asthma].
AB  - Respiratory therapy, consists in the administration of gases or drugs via
      airways; it includes: oxygen, humidity, aerosol therapy, IPPB, chest
      physiotherapy and mechanical ventilation. Asthmatic patients frequently require
      oxygen support which is delivered by low and high flow systems, for best results,
      gases must be humidified, either by bubble or wick humidifiers, heat increases
      usefulness. Spray is produced by nebulizers and metered dose inhalers, the last
      are cheaper but they need a certain grade of coordination. Powder inhalers are
      easier to use. IPPB is indicated in patients with severe fatigue, this method is
      used sporadically. Chest physiotherapy teaches utilization of relaxation and
      inferior thoracic respiration techniques. Thoracic percussion must be avoided in
      an asthmatic crisis. Mechanical ventilation is delivered through a large bore
      canule, its goal is to assure an adequate gas exchange and to avoid respiratory
      muscular fatigue.

PMID- 9005003
TI  - [Transference factor in moderate and severe atopic dermatitis].
AB  - We did a prospective, comparative, experimental study with 30 patients with
      moderate to severe atopic dermatitis from the allergy section from September 1994
      to March, 1995. The test laboratory examination was performed in all patients:
      complete blood cell count, immunoglobulins A, G, M and E determination,
      lymphocyte subpopulations CD3, CD4, CD8, CD4-CD8 proportion, CD25, rosette
      formation for B and T lymphocytes, coproparasitoscopic examination, throat and
      nose cultures, nasal cytology, skin tests of cellular immunity to PPD,
      thrichophytin, candidine, varidasa; skin prick test to poliens, fungi, inhalants
      and foods. All patients underwent to a sign and symptom grading score system as
      follows: the parameters were erythema, pruritus, eczema, papule valorated on a
      scale from 0 a 4+( O = no symptoms, + = mild, ++ = moderate, + ++= severe, ++ ++
      = very severe). Initially all patients received one placebo unit every 15 days
      orally 3 times, then one after 30 days. Laboratory examination was performed and
      then treatment with transfer factor was initiated, initially 1 unit every 15 days
      three times and the fourth 30 days after. 15 days after the last dose a new
      immunological valoration was done. Results demonstrate a CD4 cell decrement,
      blood eosinophil and lgE dissemination although they're not statistically
      significative. There was a statistically significative improvement in the 4
      clinical parameters: erythema, eczema, pruritus and populous with the use of
      Transfer Factor.

PMID- 9005004
TI  - [Predictive value of IGE in the newborn infant].
AB  - To study the relationship of IgE titles to development of allergy disease in the
      nursing, it was quantified the levels of this immunoglobulin in blood of the
      umbilical cord in healthy term eutrofic infants born consecutively in a period of
      two months. A total of 74 infants were followed for six with monthly
      appointments. The mean of IgE was 0.08 IU/ml with standard deviation of 0.15.
      Only two infants developed allergy, this determined a negative predictive value
      for IgE of 94%. Our outputs agree with that of other authors with respect to high
      negative predictive value of the low or normal levels of IgE in blood of the
      umbilical cord and the development of allergy. We concluded that its
      determination should limit to infants with family antecedent of atopy in order to
      improve the capacity of prediction of this illness.

PMID- 9005006
TI  - [Combined treatment in recurrent laryngeal papillomatosis with CO2 laser
      microlaryngoscopic resection and interferon alpha 2b].
AB  - Laryngeal papillomatosis of viral origin and bad prognosis is characterized by
      multiple recurrence that induced obstruction of air pathways. Surgical remove
      with laser CO2 is the elected treatment and the its combination with interferon
      (INF) has improved the prognosis of this recurrent viral disease. Here is a
      presents a preliminary study based upon such therapeutic scheme. Twelve patients
      diagnosed with laryngeal papillomatosis; 6 women and 6 men from 32 to 72 years of
      age were included into two therapeutic schemes: Group B, Combined: One woman and
      5 men to whom the surgical procedure was followed by a initial local dose of 3 x
      10(6) IU of INF alpha 2b (Intron A) and subsequently 10 X 10(6) (of the same INF
      were administered intramuscular every days during 15 months the statistical
      analysis (Fisher test) between patients of the both groups of treatment showed a
      significant (p < 0.0001) clinical improvement of the patients who received the
      combined treatment (B). In this group of patients was found incidence of the
      collateral effects such as: headache, fever arthralgias, depression and anorexia.

PMID- 9005005
TI  - [Hyperprolactinemia and autoimmunity].
AB  - Prolactin is a pituitary hormone with several functions, one of them,
      immunoregulatory. Patients with prolactinoma develop hyperprolactinemia. In the
      next two cases, patients with microprolactinoma, both autoimmune disease
      associated. First patient, male, with multiple sclerosis; the other one patient,
      female, with systemic lupus erythematosus. Treatment of hyperprolactinemia with
      bromocriptine was associated with satisfactory clinical evolution, and a
      reduction of dosage of immunosuppressor treatment. The patients with multiple
      sclerosis had neurological functions recovery and the patients with systemic
      lupus erythematosus had severe relapse of disease each time she dropped
      bromocriptine treatment. Pituitary function must be evaluated in autoimmune
      disease, to search alterations like hyperprolactinemia who influenced immune
      function.

PMID- 9005007
TI  - [Locoregional anesthesia for injuries of the lower limbs].
AB  - Isolated lower limb injuries are very common; difficulties for emergency
      anaesthesia may come from full stomach and drug interferences. The outcome of
      geriatric-fractured hip is influenced neither by a preoperative delay shorter
      than 48 hours, nor by the choice of anaesthetic technique; Nevertheless the use
      of acrylic cement is associated with an increased early mortality rate in
      hemiarthroplasties. Regional anaesthesia is the best choice for stable patients
      with a limited peripheral injury; The technique must be adapted to the pain
      induced by fracture; sitting position is useful for puncture. Spinal anaesthesia
      using 0.5% plain bupivacaine produces a block quickly achieved, not influenced by
      posture, allowing surgical installation and procedures. Postoperative analgesia
      using local anaesthetics may obscure symptoms of compartment syndrome which
      occasionally complicate tibial and femoral nailing.

PMID- 9005008
TI  - [Sore throat after tracheal intubation].
AB  - This study was performed to determine the incidence of sore throat 24 h after
      tracheal intubation in 1,268 patients ASA I or II, who had undergone elective
      surgery. A data form was completed. Nosing were age, sex, type of surgery,
      anaesthetic drug, muscle relaxant, number of intubation attempts, duration of
      intubation, and presence of sore throat. The incidence of sore throat was 15.06%.
      It was significantly higher in females than in males (19.29% vs 11.66%; P <
      0.01). There was a significant difference between those patients who received
      fentanyl and those who received pethidine (P < 0.05). There was also a greater
      incidence after thyroid surgery (P < 0.01). There was no correlation between sore
      throat and variables such as age, muscle relaxant, narcotic drug, number of
      intubation attempts, or duration of intubation. Lidocaine jelly and the
      appropriate analgesic drug reduce the incidence of sore throat following tracheal
      intubation.

PMID- 9005010
TI  - [Gas embolism during laparoscopy for cholecystectomy].

PMID- 9005009
TI  - [Obstetrical epidural analgesia: an epidemiological in Bourgogne and Franche
      Comte 1993].
AB  - Many publications report the number of epidural analgesias carried out for the
      last years in English-speaking countries. On the other hand, very little
      information exists about the incidence of obstetrical epidural analgesia
      performed in South and Central Europe, particularly in France. A retrospective
      study within the regions of Bourgogne and Franche-Comte was carried out for the
      year 1993 firstly, to determine the number of obstetrical epidural analgesias
      performed and the drugs used; and secondly, to describe the organization and the
      problems encountered. The result of this study leads to one major question: what
      is the best type of organization in order to guarantee the highest safety, given
      the increasing demand for epidural analgesia in obstetrics?

PMID- 9005012
TI  - [Coma caused by traumatic asphyxia: a severe neurological manifestation of
      Perthes syndrome].

PMID- 9005011
TI  - [Disseminated intravascular coagulations].
AB  - Disseminated intravascular coagulation (DIC) syndromes can be defined as the
      formation of fibrin deposits within the microcirculation, occurring in definite
      clinical situations. Their biological counterpart is a consumption coagulopathy.
      The clinical profiles of DIC have been well known for decades, are multiform and
      range from latency to overwhelming haemorrhagic diatheses, including also
      characteristic but rare situations, such as purpura fulminans, acral cyanosis and
      pictures resembling thrombotic thrombocytopenic purpura or haemolytic-uraemic
      syndrome. Biological tests of DIC show a consumption coagulopathy, displayed on
      the standard haemostasis sheet; along with signs of paracoagulation and/or of
      secondary fibrinolysis (FDP). New tests have recently been introduced: D-dimers
      are specific and sensible; Antithrombin-III, protein C and alpha 2-antiplasmin
      also can sometimes be useful. The knowledge of the pathophysiology of DIC has
      made advances with passing years. Fibrin deposits may be non-occlusive, and
      indeed they are swiftly removed by a secondary fibrinolysis. Except in very rare
      situations, such as those leading to a cortical renal necrosis, and perhaps in
      some ARDS, there is little evidence relating DIC to organ failure syndromes.
      Moreover, there is no clear relationship between the severity of the consumption
      coagulopathy and the prognosis. For instance, the mortality is much lower in
      abruptio placentae, where the coagulopathy is very severe, than in septic shock,
      where it is usually moderate. In septic shock, the disorders of haemostasis were
      related initially to a platelet activation, then to an activation of the contact
      system (releasing kinins and triggering complement cascade), and nowadays to the
      activation of the extrinsic coagulation system. The treatment of DIC is mainly
      the treatment of its cause. Indications for heparin therapy should be strictly
      limited to a few exceptional circumstances. When haemorrhagic diathesis
      threatens, FPC and/or platelet transfusion may be indicated. Aprotinin can be
      useful in rare cases of overwhelming secondary fibrinolysis. Trials with
      antithrombin-III or C1-esterase inhibitors are in progress.

PMID- 9005013
TI  - [Septic thrombophlebitis of the lateral sinus: a rare but severe complication of
      mastoiditis in children].
AB  - A case of lateral sinus thrombosis which occurred after mastoiditis in an 8 year
      old girl is reported. The elements of clinical diagnosis, the contribution of
      medical imaging and the medical and surgical management of this scarce but
      potentially severe affection are discussed.

PMID- 9005014
TI  - [Septic pericarditis caused by esophago-pericardial fistula of neoplastic
      origin].

PMID- 9005015
TI  - [Post-traumatic hypertension. Apropos of a case].

PMID- 9005017
TI  - [Value of multidisciplinary approach in the management of back pain].

PMID- 9005016
TI  - [Morphine in cesarean section and postoperative analgesia].
AB  - Epidural opioids for caesarean section are routinely used by many anaesthesists.
      Combined epidural injection of a local anaesthetic and an opioid provides a more
      rapid onset of profound analgesia. No side effects are observed in either the
      mother or the neonate with epidural "microdoses" of sufentanil or fentanyl, but
      the postoperative analgesia is of short duration. Combined intrathecal injection
      on 0.1-0.2 mg morphine and 0.5% hyperbaric bupivacaine provides a better intra-
      and postoperative analgesia. Opiates used during anaesthesia in toxemic women
      before delivery imply strict subsequent paediatric care. Good postoperative
      analgesia can be obtained with intrathecal morphine or patient-controlled
      analgesia. Using other techniques depends on care and surveillance facilities.
      Opiates by spinal or intravenous route are not dangerous for breast-fed newborns.

PMID- 9005018
TI  - [Administrative or economic regulation of ambulatory surgery units?].

PMID- 9005019
TI  - [Postoperative analgesia after surgery of the knee].
AB  - This review of postoperative analgesia after knee surgery provides a practical
      approach to the problem. The patient can be hospitalized or undergo day surgery,
      with different techniques being available for each situation. For day surgery,
      the intra-articular administration of local anaesthetic and/or opioids, the non
      steroidal anti-inflammatory drugs can be used. During hospitalization patient
      controlled analgesia, epidural analgesia and peripheral nerve blocks as lumbar
      plexus, femoral or sciatic nerve block can be proposed. It must be emphasized
      that a combined approach using these different techniques may be useful in order
      to offer better analgesia and avoid some side effects. Each technique is
      described with advantages, side effects and practical usage its. The choice, in
      each professional environment, must be the best analgesic technique which can be
      performed safely.

PMID- 9005020
TI  - [Clinical study of a mivacurium-propofol combination for laparoscopic surgery in
      children].
AB  - Coelioscopic surgery in children is today in constant progress and requires
      pharmacological agents which provide excellent surgical conditions for variable
      and unpredictable durations. The mivacurium-propofol association was clinically
      studied in this context in 30 ASA I patients aged from 6 to 16 years and appeared
      safe, efficient and easy to use. The orbicularis oculi and pollicis adductor
      stimulation allows simple and adapted neuromuscular blockade monitoring. Double
      burst stimulation at the ulnar nerve improves the detection of a residual
      curarization.

PMID- 9005022
TI  - [Epidural anaesthesia around the clock?].

PMID- 9005021
TI  - [Hypnosis and anesthesia].

PMID- 9005023
TI  - Proceedings of the 4th International Conference on Intelligent Systems for
      Molecular Biology. ISMB-96.

PMID- 9005024
TI  - [Slip technique, process dissociation model and multinomial modeling: new tools
      for experimental detection of "Freudian slips"].
AB  - The study reported here was conducted as a test of the so-called "weak Freudian
      hypothesis", which claims that unconscious thoughts are relevant for the
      generation of speech errors. Spoonerisms were induced experimentally using the so
      called SLIP technique. Motley and Baars (1976) demonstrated an increase in speech
      error rates when spoonerisms were primed semantically. The extensively discussed
      problems of "unawareness" of briefly presented stimuli were circumvented by using
      a modified version of Jacoby's process dissociation technique which allows a
      model-based estimation of conscious and unconscious processes within a task. The
      two reported experiments combined a wordstem completion task for estimating
      probabilities of perceptual processes and a SLIP task under identical perceptual
      conditions. A joint multinomial model was constructed for data analysis. The SLIP
      technique was successfully applied using German stimuli, adequate experimental
      variations raised the error rate from 7% in experiment 1 to 19% in experiment 2.
      Neither the replication of Motley and Baars' results nor unconscious priming of
      speech errors were statistically confirmed. Despite this negative result, the
      descriptive pattern of parameter estimates is psychologically meaningful: primes
      that remained unconscious resulted in a higher speech error probability than
      primes that were perceived consciously. Conscious perception might trigger
      control processes that act in opposition of speech errors. Statistical problems
      of the particular multinomial model and possible solutions in future research are
      discussed.

PMID- 9005025
TI  - [Are psychophysiologic changes in the "public speaking" paradigm an expression of
      emotional stress?].
AB  - Public Speaking is often used to induce anxiety. The emotional stress elicited by
      the anticipation of delivering a public speech, however, is usually confounded
      with the mental stress of speech preparation. In order to separate the effects of
      the emotional from those of the mental stress factor, only half of the subjects
      were informed about the topic of the speech at the beginning of the anticipation
      period, whereas the other half were told about the topic at a later time. In a
      pilot study, the effects of this variation were tested under a condition in which
      the subjects were told that the speech would be videotaped as an anxiety
      provoking and under an emotionally neutral control condition. The main experiment
      involved an additional condition with a simulated audience designed to intensify
      the impact of the emotional stress component ("strong anxiety"). Self-reports on
      present state and cardio-vascular and electrodermal responses were measured in n
      = 12 subjects in both studies. Knowledge of the speech topic did not affect the
      subjective anxiety-inducing effects of public speaking. Physiologically arousing
      effects, however, could be shown without knowledge of the topic only in some
      variables and only under the "strong anxiety"-provoking condition. In studying
      public speaking anxiety, confounding with the mental stress of speech preparation
      should therefore be avoided and a more differentiated interpretation of the
      physiological effects should be made.

PMID- 9005026
TI  - [Cardiovascular effects of active coping behavior in mental and social stress
      situations during various incentive conditions].
AB  - The main purpose of this study was to examine the cardiovascular effects of
      active coping behavior during mental and social challenge. Furthermore, the
      additional effects of monetary incentives were explored. A total of 80
      normotensive male students of the ages 19 to 30 years served as subjects.
      Statistical analyses revealed strong task-specific effects on systolic (SBP) and
      diastolic blood pressure (DBP) as well as heart rate (HR). Compared to Mental
      Arithmetic and Preparing a Discussion Task, social challenges during Discussion
      lead to exaggerated increases in SBP (37.6 mmHg) and HR (26.1 bpm) coupled with
      intermediate elevations in DBP (18.0 mmHg). Monetary incentives were associated
      with enhanced HR reactivity. The intra-task correlation pattern showed a
      remarkable across-task stability of correlations between SBP and HR reactivity
      scores, with an apparent lack of significant correlations between SBP and DBP
      reactivity scores. Results of inter-task correlations supported the hypothesis of
      specific cardiovascular response patterns that might be indicative of different
      aspects of active coping with mental and social stress.

PMID- 9005027
TI  - [Incorporation of conscience objectors in Insalud].

PMID- 9005028
TI  - [Metereology and health. The relationship between environmental temperature and
      mortality].
AB  - The results are presented of a series of recent works which analyse the
      relationships between meteorological phenomena, especially the temperature, and
      mortality. An increase in mortality in winter, is a well-known phenomenon which
      has been examined in many countries. The most common cause of death due to
      temperature changes is illness affecting the breathing apparatus and circulation
      system. The form and magnitude of the relationship between mortality and
      temperature depends on a series of factors, which include the characteristics of
      the population and the study zone. Not only the cold, but also "heat waves", have
      been associated with an increase in the mortality rate. The results of several
      works referred to suggest that the relationship between the atmospheric
      temperature and mortality take the for of a "V", with the lowest rates occurring
      on days when the average temperature is between 16 degrees and 28 degrees,
      depending on the climate in the zone being studied. An important aspect to be
      taken into account, is the delayed effect of the variations in temperature upon
      mortality. This work also refers to the role that other meteorological factors
      such as dampness and wind might play with regard to health. Finally,
      consideration is given to the potential impact on health, of temperature
      increases owing to climatic change.

PMID- 9005029
TI  - [Evolution of fecundity in the Valencian community during the 1975-1990 period].
AB  - BACKGROUND: To study the evolution of specific cases of fertility by age groups
      in the Autonomous Region of Valencia, between 1975 and 1990, and compare this
      development with the evolution on a national level. METHODS: The specific
      fertility rates were calculated for seven 5-year age groups within the female
      fertility period (15-49 years). The number of births per age of mother (Natural
      Movement of the Spanish Population) has been used and the denominator is the
      female population calculated be geometrical interpolation from the figures
      provided by different censuses and electoral roles for each one of the age
      groups. The study period is 1975 to 1990. RESULTS: The evolution of the fertility
      rate in the Autonomous Region of Valencia is declining in all age groups except
      the 30-34 year age group, where fertility showed a slight increase at the end of
      the eighties, the same as in the rest of the country. Worthy of mentioned is the
      15-19 year old group, with figures below the national level, and the 25-29 year
      old group, where the figures are greater than for the rest of the country as a
      whole. On a province (county) level, the development is similar to what has been
      described above. Alicante has the highest figure out of the three provinces
      (counties) for women in the 15-19 and 35-39 year age ranges. CONCLUSION: The
      evolution of the fertility rate in the Autonomous Community of Valencia is
      similar to the development in the rest of the country, a slight increase being
      detected in women in the 30 to 40 year group, which is similar to what has
      happened in other European countries.

PMID- 9005030
TI  - [Variability of physician changing requests in primary care of Insalud:a
      preliminary study].
AB  - BACKGROUND: The study consisted of two phases. The first phase involved analysis
      of the variability in the rates of changing doctor recorded in the Areas of
      Insalud in the first two years after Royal Decree 1575/93 came into effect,
      pinpointing some of the factors that might explain this variability. The second
      phase describes the profile of the citizens who voluntarily changed their General
      Practitioner in a Health Area, and the possible reasons for doing so. METHODS: A
      simple correlation is made between the accumulated rates of G.P. change in the
      Areas (voluntarily and owing to a change of address) and certain variables that
      were presumably associated with this, together with a systematic sampling of the
      voluntary changes recorded in Area 5 Madrid, for the first three-monthly period
      in 1994, and a description of the characteristics of both the patients involved
      and their former doctors. RESULTS: The two-yearly rates of voluntary change in
      Areas (1.73-18.87 changes for every 100 cards) are correlated with the following
      variables: lower ageing of the population, number of inhabitants/doctor,
      frequency of visits, proportion of evening surgeries and population concentration
      on the Area. These last three variables are also correlated with the rates of
      change of address in the Areas (0.62-7.35 changes for every 100 cards). By
      contrast, no correlation was to be found between the two rates of change, neither
      was there any correlation between them and the extension of the cover through
      Primary Aid Teams. Those who requested to change doctors in the Area studied,
      were differentiated from the rest of the population in the Area because of their
      age (there was a larger number of elderly people and less adults than were
      expected) and zone of residence (more urban and less rural). Most of the patients
      did not change the model but did change their surgery visiting hours (the tended
      to change to the evening surgery), but these latter differences where not
      statistically significant. CONCLUSIONS: The rate for changing one's G.P. in the
      Areas, bears no relationship to the setting up of Health Centres, but rather with
      factors that are present in the urban Areas (population concentration and an
      increase in the offers of assistance), which were conducive to the use of the new
      legislation by citizens, especially those who are users of the services.

PMID- 9005032
TI  - [Tobacco addiction in primary health care workers in the health area number 4 of
      Insalud in Madrid: prevalence of consumption and attitude].
AB  - BACKGROUND: In developed countries, tobaccoism constitutes the main public health
      problem capable of prevention. Health professionals comprise the sector with the
      greatest power of influence in reducing smoking habits. Nevertheless, cooperation
      is determined by their own personal habits and attitudes to smoking. This study
      describes the prevalence of smoking and attitudes towards tobaccoism amongst
      primary medical care personnel within Area 4 of Insalud in Madrid. METHODS: Of
      the 910 workers surveyed, 803 responded (response rate: 88%). 42.3% were smokers
      (35.3% on a daily basis and 7% occasionally) and the average smoker consumed 17
      cigarrettes per day. 25.9% were ex-smokers and 31.7% non-smokers. 95% of non
      smokers and 85% of smokers considered that smoking should be forbidden in medical
      centres (p << 0.001). 11% of smokers did so in front of patients (10% of doctors
      and 3.3% of nursing staff). 58.4% of smokers stated that they would participate
      in an assistance scheme designed to help them give up the habit. CONCLUSIONS:
      Results indicate that there still exists a large percentage of primary medical
      care personnel that smoke and that attitudes are not those that would be expected
      from a group of people seen as an example by others. Priority must be given to
      intensifying awareness, assisting people to give up smoking and to training
      courses.

PMID- 9005031
TI  - [Long-term effectiveness of anti-smoking counseling in primary care: the relapse
      process].
AB  - BACKGROUND: Addiction to tobacco is the main cause of preventive morbidity, and
      so the fight against tobacco consumption is a priority in the developed world.
      Health advice is a valuable tool in this struggle and it is within the reach of
      all health workers. To study the long-term effectiveness of all anti-tobacco
      advice in Primary Aid, together with the influence that the reason for giving up
      (spontaneous or after advice) has upon the relapse pattern. METHOD: We carried
      out a clinical test on 501 patients, 242 as a participant group, receiving health
      advice, and 259 in a control group. We evaluated giving up the habit through a
      survey. The data were analysed by means of a study with a survival study,
      considering the relapse to be the final point. Survival curves for the two groups
      were compared with the Lee-Desu statistic. RESULTS: 115 patients gave up the
      habit for at least 24 hours (31.8% from the participant and 14.7% from the
      control group). After 3 years, after a biochemical check-up, 4.5% of the
      participant group and 1.2% of the control group were still ex-smokers (difference
      = 3.3; p = 0.043%; there is a confidence interval of 95%: from 0.45 to 6.33). We
      did not find significant differences between their survival curves (p = 0.08).
      CONCLUSION: We have been able to confirm the mid- to long-term effectiveness of
      anti-tobacco advice. We have not been able to demonstrate that anti-tobacco
      advice in the relapse pattern, but a statistical trend does exist towards a
      reduction in the participant group.

PMID- 9005033
TI  - [Epidemic outbreak of 81 cases of brucellosis following the consumption of fresh
      cheese without pasteurization].
AB  - BACKGROUND: In spite of the great effort that has been made in recent years in
      Castilla-La Mancha to control brucelosis, a lack of awareness on the part of
      producers and consumers leads to major epidemic outbreak, such as the one
      described below. METHODS: A description of the outbreak is described and a study
      is conducted of cases and controls to determine the factors which are responsible
      for the epidemic. Unadjusted and adjusted Odds Ratios (O.R.) are obtained
      together with their confidence intervals, for the main epidemiological factors
      studied. RESULTS: A total of 81 cases of brucelosis were recorded in a period of
      25 weeks. All the cases occurred in the same borough or were in some way linked
      to it. In the case and controls study no differences were found with regard to
      age, sex, contact with livestock or the consumption of pasteurised milk or
      cheese. A strong link was established between the illness and the consumption of
      home-made cottage cheese prepared by a small-scale producer in the borough, (O.R.
      = 311.9; C.I. = 95% = 41.48-12735)., whose livestock turned out to be infected
      with Brucella Mellitensis. CONCLUSIONS: This outbreak showed that in Spain, there
      is a risk of contracting brucelosis by consuming non-pasteurised dairy products,
      particularly cheese, when these are not subjected to the normal sanitary and
      health controls. The benefits of epidemiological research in the search for cases
      and determining the factors responsible for the outbreak are also demonstrated.
      An intensification of controls, the cleansing of the herds and flocks and health
      education in general, are suitable instruments for controlling this zoonosis in
      Spain.

PMID- 9005034
TI  - [Serologic study of vertically transmitted infections in pregnant women attending
      3 health centers in Jaen].
AB  - BACKGROUND: Studying serological tests into syphilis, German measles, toxoplasma
      and hepatitis B requested as part of the monitoring of pregnant women and
      analysing the different activities in the face of the findings. METHODS: A
      descriptive study. A systematic random process was used to select (1/3) 299 cases
      of women whose pregnancy had been monitored between 1991 and 1993 in three health
      centres in Jaen (capital of the province of the same name), which have a
      catchment population of 66,423 inhabitants. We analyse the differences between
      the centres using the Chi squared test. RESULTS: A serology of syphilis (R.P.R.)
      was conducted on 269 pregnant women (90% Standard Error (S.E.): 1.7) all of which
      proved negative; German measles (ELISA Immunoglobulin (Ig) G, toxoplasm (FIAX IgG
      and IgM) and (HBsAg in 92% (S.E.: 1.6) German measles antibodies being found in
      98% (S.E.: 0.8), the HBsAg proving negative in 99% (S.E.: 0.6) and immunity to
      toxoplasm existing in 13% (S.E.:2). When the data were analysed, being broken
      down into the different health centres, notable differences were observed (p >
      0.04) in the case of German measles. In the five cases were German measles proved
      negative, the serology was not repeated once, and on two occasions it was the
      second pregnancy. They do not appear in the history of preventive medicine.
      Treatment with spiromycine was initiated for toxoplasmosis, and it lasted for 10
      to 21 days for five of the cases, but the infection was not confirmed once, and
      for two of these it was only determined serologically. CONCLUSIONS: Both the
      percentage of requests for the first serology and the prevalence are consistent
      with literature on the subject, with the exception of toxoplasm, whose immunity
      prevalence was much lower than in other zones. The actions taken in the face of
      certain results were rather inadequate.

PMID- 9005035
TI  - [Determination in blood and urine of the recent non-therapeutic consumption of
      psychotropic substances in patients being admitted to the psychiatric unit of a
      general hospital in Valencia].
AB  - BACKGROUND: An increasing trend in the consumption of psychoactive substances has
      been observed in psychiatric patients who are hospitalised. The aim of this
      research is to establish the prevalence and the characteristics of the recent and
      non-therapeutic consumption of these substances, by detecting their presence in
      the blood and urine of psychiatric patients admitted to hospital, the influence
      of such consumption on the clinical manifestations of the mental disorders and to
      recommend criteria for such a phenomenon. METHOD: Detection of cannabis,
      amphetamines, opiates and cocaine, using the ADX system, and in blood through the
      REA system for alcohol detection, in patients admitted to the Psychiatric Unit of
      the General University Hospital in Valencia, during the first six months of 1995.
      The diagnoses were based on the CIE-10 in its research version, and the influence
      of the consumption of substances detected in the clinical manifestations of the
      disorders was determined by the majority decision taken be three experienced
      psychiatrists. RESULTS: the prevalence detected in the consumption of
      psychotropic substances is high (almost one third of those admitted), and
      consumption played a part in the admission of most of these patients (nearly
      89%), aggravating the mental disorder problem when they were admitted. The
      variables that were most often associated with the consumption detected, where
      males hospitalised as a result of a brush with the law. CONCLUSIONS: A routine
      determining of the presence or absence of substances liable to abuse is
      recommended in patients admitted to psychiatric institutions.

PMID- 9005036
TI  - [Dietary and personal hygiene habits of adolescents in a rural population].
AB  - BACKGROUND: A healthy diet and adequate personal hygiene are essential factors
      for good health. Adolescents gradually achieve a degree of autonomy in these
      areas. The aim of the study is to find out the diet and hygiene habits of
      adolescents in Navalcarnero, a rural town in the Autonomous Region of Madrid
      (Spain). METHODS: A descriptive study of a cross section of the relevant
      population, by previously validated, self-completed and anonymous questionnaire,
      filled in by adolescents (3 degrees BUP/ESO/FP) in by 13- and 14-year old school
      children (EGB.) The diet survey assessed the weekly consumption frequency of
      different foodstuffs. RESULTS: The respondents normally had milk and cocoa for
      breakfast, with toast or a bun. Lunch was more abundant than the evening meal,
      and more fruit was consumed more often in the former. Most of the children drank
      milk every day, usually in its natural state, but in two out of three cases, the
      consumption of dairy products was not as recommended, vegetable consumption was
      low. Among the children of BUP/ESO/FP, the girls consumed greens, salad, fruit
      and sliced bread more often, this difference being particularly marked in the
      case of the bread, and the boys consumed considerably more meat and bread of the
      French-stick kind. With respect to personal hygiene, most of them have a shower
      and wash their hair every two or three days and brush their teeth and change
      their underwear on a daily basis; the girls proved to be much more assiduous in
      having a shower, brushing their teeth and changing their underwear. CONCLUSIONS:
      In some areas, behaviour as regards diet and hygiene shows differences depending
      on the sex of the individual, certain habits ought to be improved upon.

PMID- 9005037
TI  - [Tuberculosis tracing in Moroccan immigrants].
AB  - BACKGROUND: Tuberculosis has reappeared in developed countries, and Spain is no
      exception. The aim of this study is to find out the degree of prevalence of
      tuberculosis infection and the rate of tuberculosis infection in a shanty town
      occupied by Moroccan immigrants. METHODS: Using one case of active pulmonary
      tuberculosis in a Moroccan citizen, immigrant and resident in a settlement of
      slums, a contact study was undertaken with the collaboration of social workers
      and a Moroccan sociologist who lived in the same shanty town, who acted as
      interpreter. A tuberculosis test was carried out applying PPD in the Health
      Centre, to 80% of the residents, offering an extremely flexible timetable and no
      bureaucratic red tape. The inoculations, records and Mantoux readings were
      performed by two nurses at the Health Centre. RESULTS: Mantoux cover was 83.3%.
      The proportion with a tuberculosis infection was 77.7%; five cases were diagnosed
      as pulmonary tuberculosis (13.8%). CONCLUSIONS: The rate of tuberculosis found
      (77.7%) is considerably higher than other findings published with respect to
      other fringe groups living in Spain (30%).

PMID- 9005038
TI  - [Excimer laser photorefractive keratectomy in myopia and astigmatism--1 year
      experience].
AB  - The authors evaluate the results of photorefractive keratectomy by means of an
      excimer laser myopia and astigmatism in 343 eyes with a minimal follow-up period
      of 9 months. The value of the preoperative refractive error expressed in
      spherical equivalents was -1,75 to -18,5 d. In astigmatism the maximal value was 
      5 cyl. d. The group was divided into four sub-groups: A) -1,75 to -3,0 d., B) 
      3,25 to -6,0 d., C) -6,25 to -10,0 d., D) more than -10,25 d. The spherical
      equivalent of the refractive error 9 month after operation was -0,28 d. in group
      A, -0,37 d. in group B, -0,67 d. in group C and -1,82 d. in group D. Uncorrected
      vision, 6/12 or better, 9 mons after operation was recorded in group A in 98,1%
      patients, group B 95,6% group C 91,2% and in group D in 72,5% patients. The
      authors proved a high effectiveness, safety predictability and stability of
      photorefractive keratectomy by means of an excimer laser in myopia up to -10 d.
      Photorefractive keratectomy is a promising method which extends the possibilities
      of correcting myopia and astigmatism in sufficiently positively motivated and
      indicated patients.

PMID- 9005040
TI  - [Survival in patients with malignant melanoma of the uvea].
AB  - In the study is given the analysis of the data of patients with malignant uveal
      melanoma from the tumor register of the Dpt. of Ophthalmology of the Med.
      Faculty, Comenius University, Bratislava, Slovak republic, in years 1988-1993. In
      this period there are registered 94 patients with malignant uveal melanoma, 0,86%
      of all treated patients. There are registered 22 cases (8,2%) in iris, in corpus
      ciliare 13 (13,8%), in chorioidea - 72 (76,6%). In this 6-years period 74 cases
      (78,8) were treated by radical surgical techniques (enucleation, block-excision),
      in 18 cases (19,6%) brachytherapy by episcleral beta-applicator (Ru106/Rh106) was
      used and 2 of the patients (2,1%) refused any kind of therapy. Follow-up 3 months
      to 6 years: life expectancy-we didn't mention significant difference in the
      mortality-rate in the group of 72 patients treated by radical surgical techniques
      and those (18 cases), who were treated by episcleral applicator (Kruskall-Wallis
      test). The mortality rate was 25% in group A (enucleation) and 33% in group B
      (beta-irradiation).

PMID- 9005039
TI  - [Histologically verified intraocular tumors in the Slovak Republic 1984-1989].
AB  - In the study is given the analysis of the data of patients with dg. 190 (ICD-9)
      from National Oncology Registry in Slovak Republik in period 1984-1989; the
      number and the portion of histologically identified intraocular tumors in regions
      of Slovakia; the data were completed by number of patients from registered
      announcements of decreases. In 6-years period is registered 278 cases; average 46
      cases; the incidence was 0,9/100.000 inhabitants. Microscopically identified were
      257 cases (92%). The percentage of microscopically verified cases in regions was
      from 76% to 100%; we didn't mention the difference between men and women. In the
      last 2 years the rate of microscopically cases was relatively lower than before.
      The data completed from the registered announcements of decreases (dissection
      findings) had no influence to increase the proportion of microscopically
      identified cases.

PMID- 9005041
TI  - [Diagnosis of chronic conjunctivitis].

PMID- 9005042
TI  - [Treatment of chronic conjunctivitis].

PMID- 9005044
TI  - [Use of liquid perfluorocarbons in ophthalmology].

PMID- 9005043
TI  - [Central serous chorioretinopathy].

PMID- 9005045
TI  - [50 years of the Eye Clinic in Hradec Kralove].

PMID- 9005046
TI  - [Diseases of the orbit in children].
AB  - The authors analyze their 8-years experience and therapeutic results achieved in
      78 hospitalized children with different pathological conditions of the orbit. The
      spectrum of diseases comprised in 38% congenital anomalies, 22% tumors, 22%
      traumatic accidents, 13% was for orbital manifestations of systemic disease and
      in 5% inflammatory processes participated. The majority of patients were operated
      and the remainder was treated by conservative methods. The therapeutic results
      and other important aspects of orbital diseases are discussed.

PMID- 9005047
TI  - [Changes in the conjunctiva and cornea in dialyzed patients].
AB  - The author examined 119 patients having regular dialyzation treatment and a
      control group of 90 healthy subjects, divided into groups by decades. Depending
      on the intensity of pathological changes, they created four categories; the fifth
      comprised normal findings. The prepared from the bioptic material of the
      conjunctiva of two patients preparations which were examined for calcium and
      amyloid deposits. Pathological changes were found in 74.8%. The authors try to
      explain the cause of conjunctival and corneal changes, consistent with the theory
      of hastened ageing in chronic renal failure of patients treated by regular
      haemodialysis. The so far unique findings of amyloid of the conjunctiva could be
      possibly used in future for the diagnosis of amyloidosis instead biopsies.

PMID- 9005048
TI  - [Dystrophic changes in the macular pigment epithelium as a sequela of exudative
      diabetic maculopathy].
AB  - This work is concerned with the treatment of diabetic exsudative maculopathy
      using hypolipemic and laser therapy. It shows correlation between the decrease of
      lipemia and the reduction of the area of hard exsudates in the central region of
      retina after the hypolipemic therapy. But the corresponding improvement of the
      vision could not be reached because in 31.2% of cases there were permanent
      changes of the pigment epithelium of central retina in the original locations of
      the hard exsudates.

PMID- 9005049
TI  - [Decompression of the optic nerve sheath--results in the first 37 operated eyes].
AB  - The authors present results of optic nerve sheath decompression in 37 eyes. The
      decompression surgery was performed for progressive form of anterior ischemic
      optic neuropathy (AION) in 11 eyes, AION combined with central retinal vein
      occlusion in 2 eyes, low tension glaucoma in 7 eyes (+1 reoperation), central.
      retinal vein occlusion in 1 eye, optic nerve head drusen in 11 eyes, chronic
      optic disc edema in pseudotumor cerebri in 3 eyes, amiodarone optic neuropathy in
      1 eye. Postoperative findings (visual acuity and visual field) are presented for
      each diagnosis. After surgery a transient double vision developed in 5 patients.
      We have not seen any other complications. Optic nerve sheath decompression is a
      controversial method of treatment for optic neuropathies. We advocate this method
      of treatment for vision-threatening optic neuropathies after thoroughly balanced
      assessment of possible risks and gains.

PMID- 9005051
TI  - [Acute retinal necrosis syndrome].
AB  - Necrotizing herpetic retinopathies are serious, usually rapidly progressive
      diseases of retina. Three well defined syndromes can be outlined: acute retinal
      necrosis, progressive outer retinal necrosis and CMV retinitis. Two cases of
      acute retinal necrosis, where the clinical picture was probably influenced by the
      corticosteroid use are described. The overview of clinical manifestation and
      therapy of these syndromes is given.

PMID- 9005050
TI  - [Amiodarone neuropathy of the optic nerve from the viewpoint of the neuro
      ophthalmologist].
AB  - The authors present an account on an uncommon case when damage of visual
      functions of a patient were due to two independent cause: amiodarone neuropathy
      of the optic nerve (ANO) and an intracranial tumour-a craniopharyngioma.
      Effective treatment of both diseases achieved marked improvement of visual
      functions. The authors want to draw attention to the fact that one disease which
      theoretically would be sufficient to explain impaired vision, is not necessarily
      the only disease from which the patient suffers. Comprehensive examination is
      always essential.

PMID- 9005052
TI  - [History of ophthalmologic hospital departments in the Czech Republic].

PMID- 9005053
TI  - [The 2nd Eye Clinic of the Pediatric Eye Clinic in Motol].

PMID- 9005055
TI  - [Ambulatory cataract surgery].
AB  - The authors present an account of the experience with the first one hundred out
      patient cataract surgery which were performed at the Second ophthalmological
      Clinic in 1993 and 1994. They found that the only absolute contraindication is
      the need to administer general anaesthesia and they discuss the main problems
      which ensue from the present state of the health services and society as a whole.

PMID- 9005054
TI  - [Surgical activity at the 2d Eye Clinic 1985-1994].
AB  - During 10 years the annual number of operations increased by 87%. The number of
      cataract surgery raised more than twice. A change of surgical techniques was
      seen: from intracapsular cryoextractions to extracapsular surgery with
      intraocular lens implantation and finally to phacoemulsification. The number of
      glaucoma operations increased markedly in accordance to the good results of early
      surgery. More than four times increased the number of pars plana vitrectomies.
      Further development of surgery is limited by space problems.

PMID- 9005056
TI  - [Phacoemulsification in high myopia].
AB  - In 39 eyes of 26 patients with a baseline refraction of -6 to -28 dioptres
      phacoemulsification with implantation of an intraocular lens was performed.
      During the 3-23-month follow-up period there was no case of detachment of the
      retina no development of clinically significant secondary cataract. The resulting
      refraction of the eyes was +1 to -6 from the intended refraction. In none of the
      patients deterioration of visually acuity was recorded.

PMID- 9005057
TI  - [Vitreous surgery in complicated retinal detachment].
AB  - Vitreous surgery in complicated retinal detachment has three main objectives: 1.
      elimination of traction and mobilization of the retina, 2. inner tamponade of the
      retina, 3. retinopexy. Pars plana vitrectomy with inner tamponade is indicated:
      1. In rhegmatogenous retinal detachment, where vitreous hemorrhage or exsudate
      make the finding and localization of the retinal break impossible. 2. In
      rhegmatogenous retinal detachments, where the localization of the break in the
      posterior eye pole or the size of a giant tear prevent to close the retinal break
      by means of a cryosurgical procedure with episcleral plombage. 3. In retinal
      detachment complicated by advanced proliferative vitreoretinopathy: in idiopathic
      rhegmatogenous detachment, tractional detachment after perforating injury, and in
      diabetic retinopathy. Vitreous surgery increased the limits of operability in
      complicated retinal detachments.

PMID- 9005058
TI  - [The establishment of the Eye Clinic at the Charles University Medical School
      Hospital in Prague].

PMID- 9005060
TI  - [Professor Jaromir Kurz and his school].

PMID- 9005059
TI  - [Pars plana vitrectomy in retinal detachment with a macular hole].
AB  - The long-term results of pars plana vitrectomy (PPV) for retinal detachment due
      to a macular hole were evaluated in 40 eyes of 40 patients. The patients were
      followed up for 6 to 72 months. In 9 eyes, subtotal PPV with expansive gases was
      used: in 5 of them, in addition, the macular hole was treated with laser
      endocoagulation. The operation was successful in 4 out of 5 eyes treated with
      laser barrage. In the remaining 5 eyes, the operation failed and reattachment was
      obtained after secondary silicone oil implantation (SOI). In 31 eyes, PPV was
      combined with a primary SOI. Twenty of them suffered from serious myopic
      degenerative changes of the posterior eye pole, and in 11 posterior stafyloma.
      Reattachment of the retina was achieved in 28 eyes (90.3%), visual acuity 1/24
      (0.04) or better in 13 eyes (41.9%). Silicone oil was removed in 13 eyes (41.9%),
      in all these without complications. PPV with expansive gases and laser
      coagulation proved to be effective in macular holes with the well-preserved
      pigment epithelium. Silicone oil proved competent in macular holes associated
      with serious chorioretinal degeneration and posterior stafyloma.

PMID- 9005062
TI  - [The epidemiology and risk factors of diabetes mellitus in the region of the
      Ukrainian Carpathians].
AB  - The existent prevalence has been studied of diabetes mellitus (DM) in the
      territory of the Ukrainian Carpathians with special reference to DM types as well
      as climatic and geographic features of the region, according to the Saint Vincent
      Declaration Programme. As per 1st January, 1994, DM was diagnosed in 9321
      patients, the index of DM prevalence (per 100,000) having been 866.1. Difference
      in index of DM prevalence among residents of low-mountain and median-mountain
      ranges, median-mountain and high-mountain ranges is clearly tending downwards
      (0,05 < P 0,1). Morbidity in the population of the high-mountain ranges is more
      than two times as low as that in the low-mountain range. The most significant
      risk factors appear to be age over 40, obesity, hypertensive disease, IHD,
      hypercholesterolemia, as well as some impacts from the surrounding environment
      provoking DM development in hereditary predisposition to this medical problem.

PMID- 9005061
TI  - [The mechanism of the effect of insulin on the interhormonal relations of
      androgens and glucocorticoids in the body].
AB  - Forty-six essentially healthy persons, 96 patients with carcinoma of the stomach
      (stage II, III and IV), 26 patients with idiopathic aseptic necrosis of the head
      of the femur and 42 patients in the time course of their medical condition
      related to traumata were studied for changes in the excretion of metabolites of
      androsteroidogenesis and glucocorticoids under the influence of insulin. It has
      been established that insulin actions on steroidogenesis depend upon
      interhormonal relations of androgens and glucocorticoids under their values being
      low, insulin stimulates androsteroidogenesis and reduces the production of
      glucocorticoids, while their high values are associated with activation of
      hypothalamic-pituitary-adrenal axis due to insulin hypoglycemia, with the
      production of glucocorticoids rather that androgens tending to be on the
      increase. There has been revealed for the first time the ability of insulin to
      stimulate, under dyscorticism, androsteroidogenesis and lower the production of
      glucocorticoids, which facts permit recommending the use of insulin to lessen
      catabolic, contrainsular, and immunodepressive effects of glucocorticoids in the
      organism.

PMID- 9005063
TI  - [The correlation of the hormonal and clinical effects in patients with prostatic
      cancer undergoing niftolid treatment in combination with low doses of synestrol].
AB  - Effects were studied of niftolide in tablets, 0.25 g on a three-times daily basis
      in combination with low doses of sinestrol, 5 mg intramuscularly within 24 h, on
      tumor growth, blood plasma content of luteinizing hormone (LH), testosterone (T)
      and testosterone-estradiol-binding globulin (TEBG) in 46 patients with prostate
      gland carcinoma, including seven patients with metastases. After treatment for
      three months, plasma T level decreased by 63%, that of LH by 53% whereas TEBG
      increased twice as much. The treatments were administered for as long as 10
      months, with estrogen therapy being tapered to a dose of 3 mg daily. The above
      treatment schedule resulted in stabilization or partial regression of tumor
      growth in as many as 94.9% cases; also deserving to be noticed was improvement in
      the outflow of urine and alleviation of the pain syndrome. The clinical effect is
      believed to be due to pharmacological blockade of androgenic receptors in the
      tumor and its metastases as well as to antigonadotropic activity of estrogen and
      striking lowering of blood plasma free T.

PMID- 9005064
TI  - [The efficacy of enterosorption in an intensive contamination by radionuclides].
AB  - There has been tried in the treatment of those individuals (n = 259) actually in
      the ChNPS zone in May-June 1986, the enterosorbent CKH. Enterosorption in the
      complex of therapeutic measures applied for those patients presenting with
      intensive contamination with radionuclides provides effective detoxication,
      improves the functional state of the liver and kidneys, makes for a rapid
      elimination of radionuclides both by their direct adsorption in the intestinal
      lumen and mediate mechanisms, which effects lower morbidity rates in early
      periods after radioactive contamination.

PMID- 9005066
TI  - [Iridodiagnosis in diseases of the hepatobiliary system and kidneys].
AB  - Overall fifty patients with chronic hepatitis and 50 patients with concurrent
      pathologies were examined. The patients with chronic active hepatitis and in
      coexisting pathologies showed more profound depression of the immunity system as
      well as striking alterations on the iris of the eye. The former patient group
      received basic therapy, while the latter one were given immunomodulating agents
      against the background of basic therapy. Iridodiagnosis will, we believe, help in
      detecting concurrent pathologies of the hepatobiliary and urinary systems. The
      dynamics of the pathological signs in the iris is strongly related to the
      clinicoimmunological picture of the illness. Iridodiagnosis is a reliable test of
      a therapeutic effect in patients with chronic diseases of the hepatobiliary
      system and in those cases having this medical problem concurrently with the
      urinary system pathologies.

PMID- 9005065
TI  - [Lipid peroxidation and blood serum peroxidase activity in diseases of the
      hepatobiliary system].
AB  - Patients with hepatobiliary pathology showed an augmentation of peroxide
      oxidation of lipids (LP), its degree dependent upon the severity of the clinical
      course of the medical condition in question, being the highest in those patients
      with viral hepatitis, carcinoma of the head of pancreas, and portal cirrhosis of
      the liver. A parallel investigation into the blood serum peroxidase activity, the
      main indicator of the antioxidant activity, in the above patients, showed a
      noticeable decrease in PA activity. LP and blood serum PA measurements allow some
      judgement about the gravity of the course of hepatobiliary pathology and
      effectiveness of the therapy adopted.

PMID- 9005067
TI  - [The combined x-ray-endoscopic evaluation of the late results in organ-preserving
      operations with vagotomy in peptic ulcer].
AB  - The article gives an objective assessment of remote results of surgical treatment
      of 197 patients who underwent organ-sparing operations combined with vagotomy for
      ulcer disease. Combined utilization of contemporary roentgenologic and endoscopic
      techniques allowed some important conclusions of practical value to be drawn.

PMID- 9005068
TI  - [The use of microwave resonance therapy in the health-resort treatment of peptic
      ulcer].

PMID- 9005070
TI  - [The use of mildronate and trental in treating disorders of hemorheology and the
      intracardiac hemodynamics in patients with chronic obstructive bronchitis].
AB  - Overall ninety patients with chronic obstructive bronchitis presenting with signs
      of pulmonary-cardiac insufficiency (CPI) were studied by static radionuclide
      ventriculography with pertechnetate and rotation viscosimetry before and after a
      14-day course of treatment. All the patients received basic treatment with
      cardiac glycosides on a differential basis depending upon CPI severity. Those
      patients having been prescribed mildronate additionally in a daily dose of 10
      mg/kg body mass demonstrated improvement in left ventricular performance: the
      total and regional ejection fractions got increased, with the end-diastolic and
      end-systolic volumes having gotten reduced. Those patients receiving mildronate
      combined with thrental at a daily dose of 7-8 mg/kg body mass showed improvement
      in rheologic properties of blood as well as in intracardiac haemodynamics. At the
      same time, the right and left ventricles of the heart improved their performance,
      with their dysfunction having been lessened: the total and regional ejection
      fractions appeared to be increased, the end-diastolic and end-systolic volumes
      reduced, the amplitude-time characteristics of the processes of ejection and
      filling of the ventricles of the heart were found out to get better.

PMID- 9005071
TI  - [Atypical pleural syndromes].
AB  - Common somatic and vegetative innervation supplying the pleural and abdominal
      cavities and organs thereof, as well as wide nervous communications between the
      above cavities and organs in many instances of pleural exudate and spontaneous
      pneumothorax lead to a clinical manifestation with false syndromes, to which
      syndromes the author applies the term "atypical syndromes". The proposed
      categorization of syndromes will, we believe, help the physicians who examine the
      patients on a primary basis, to avoid possible errors in the policy of examining,
      diagnosing and treating patients.

PMID- 9005069
TI  - [The methods and principles for ultrasonic study of the digestive tract].
AB  - The paper addresses issues of preparation of patients for ultrasound
      investigation of the stomach and bowels. Echographic structure of hollow organs
      in the norm is presented. Approaches to examining different portions of the
      stomach and intestine are outlined.

PMID- 9005073
TI  - [Eosinophilic reactions in bronchial asthma patients and the possibilities to
      neutralize them under sanatorium treatment].
AB  - Patients with eosinophilic variant of bronchial asthma demonstrate high levels of
      fibrinolytic activity in their bronchial secretion along with low content in same
      of Ig A, as evidenced by findings obtained in the course of sanatorium treatment.
      There is usually no correlation between the above changes and routine methods of
      health resort treatment. The judicious employment in a complex of therapeutic
      measures of aerosols of hydrocarbonate of sodium and heparin promotes
      neutralization of cationic proteins and large major protein of eosinophiles in
      the bronchial lumen whereby there occurs normalization of Ig A levels in the
      sputum along with lowering of its fibrinolytic activity.

PMID- 9005072
TI  - [The energy characteristics of cardiorespiratory system function in patients with
      chronic bronchitis under graded physical loads].
AB  - On the basis of 38 spiroveloergometries performed in 20 patients with chronic
      bronchitis (ChB) there have been calculated energy characteristics of the
      function of the cardiorespiratory system (power of the heart, respiratory muscles
      and erythron, effectiveness of capturing of oxygen in the cardiac, pulmonary,
      erythron links and in the oxygen transport system as a whole) while they were
      doing their graded exercise. Mathematical simulation (factor analysis) permitted
      identification of two levels of work load (> and < 80 Wt) differing widely in
      their physiological and energy maintenance. A conclusion is substantiated and
      validated that loads under 80 Wt appear to be preferable, corresponding to the
      area of optimal, in terms of energy maintenance, functioning of the
      cardiorespiratory system of ChB patients (strategy of increasing the oxygen
      consumption at the expense of the predominant augmentation of the adequate volume
      in proportion to enlargement of the stroke volume).

PMID- 9005074
TI  - [The efficacy of using antiaggregants in chronic glomerulonephritis with grade-I
      chronic kidney failure].
AB  - Both short-term and long-term effectiveness of xantinole nicotinate as well as
      trentale and combinations thereof with dipyridamole has been demonstrated in
      patients with chronic glomerulonephritis presenting with grade 1 chronic renal
      insufficiency, which fact can be accounted for by their vasoactive and
      antiaggregant actions. Particular regimens have been developed to treat the
      medical condition in question with the above drug preparations, comparative
      evaluation was done of their effects on the clinical course of the illness as
      well as on the effective renal plasma flow, concentration of nitrogenous
      remainder in blood and urine, concentration of medium size molecules in blood. It
      is advisable that antiaggregants be administered long term (from several months
      to several years).

PMID- 9005075
TI  - [Renal blood circulation in patients with vasorenal hypertension (based on
      ultrasonic dopplerography data)].
AB  - In an evaluation of 25 patients, Vmax, Vmin, ratio in the stenosed renal artery
      (RA) was found to be significantly lower as compared with RA of control group
      patients, whereas the contralateral RA did not show any changes in the above
      parameter. Thus, under unilateral RA stenosis, there is an upward tendency in the
      difference between the values for stenosed RA and contralateral RA. Estimators of
      asymmetry appear to be significantly higher in main group patients, which fact
      suggest to us that results from doppler ultrasonography might provide an
      additional index to be taken into consideration in a setting where a patient is
      to undergo angiography.

PMID- 9005076
TI  - [The use of the Zubova-Stuart method of bioinformation therapy in sexology
      practice].

PMID- 9005078
TI  - [The treatment of atypical manias with finlepsin-retard].
AB  - The article presents results of clinical trial of finlepsine-retard. Objectivized
      parameters characterizing the time course of psychopathologic symptoms were
      studied in certain concentrations of finlepsine and beta-endrofin in blood serum.
      Atypical maniac states do not easily respond to therapies but finlepsine-retard
      gives the modern psychopharmacotherapy a new horizon.

PMID- 9005077
TI  - [The pentoxifylline and corglycon treatment of patients with circulatory
      encephalopathy against a background of atherosclerotic lesions of the major
      cerebral arteries].
AB  - As many as 34 patients having stage II-III atherosclerotic dyscirculatory
      encephalopathy with coexisting ischemic heart disease in the presence of
      stenosing and occlusive lesions of major brain arteries were evaluated for
      effects pentoxiphyllin and corglycon on the clinical course of this medical
      condition as well as systemic and cerebral haemodynamics. In this series, 82.7
      percent of patients derived benefit from a single intravenous infusion of
      pentoxiphyllin and corglycon and course treatment with these drug preparation
      that was evidenced by an improvement in the parameters of systemic and cerebral
      hemodynamics and regression of neurologic symptomatology. The results of the
      studies made permit recommending pentoxiphyllin in combination with corglycon for
      treatment of those DE patients with eukinetic and hypokinetic types systemic
      haemodynamics, whereas pentoxiphyllin alone--for those with hyperkinetic type of
      haemodynamics, taking into consideration its cardiodepressive effects.

PMID- 9005079
TI  - [Enterovirus infections in Ukraine].
AB  - An analysis has been done of isolation of enteroviruses from infectious patients
      with various diagnoses, as well as from those persons examined on epidemiological
      indications, and healthy children over a period of twelve years (1980-1992).
      There have been determined serotypes of enteroviruses prevailing in one or
      another form of infection as well as in healthy (asymptomatic) carriers.
      Enteroviruses were shown to have a potential role in the etiology of a major
      portion of those medical conditions diagnosed as serous meningitis,
      neuroinfection, ARVI, and others.

PMID- 9005080
TI  - [The clinical manifestations of heat-induced lesions in miners in the deep coal
      mines of the Donets Basin].
AB  - Heat-induced lesions in miners are characterized by syndrome of vegetovascular
      dysfunction presenting with a damage to the segmental and suprasegmental
      structures of the vegetative nervous system, worsening of the bodily heat status,
      decrement of physical performance. A distinguishing feature of vegetovascular
      dystonia in acute overheating is activation of sympathicus, while in chronic one
      that of parasympathicus. By patterns of function disorders and degree of their
      restoration acute overheating can be categorized into the following forms-mild,
      moderately severe and severe ones. In chronic overheating distinct syndromes are
      recognized depending upon the particular course of vegetovascular dysfunction,
      viz., permanent course vegetovascular dystonia, permanent paroxysmal one
      presenting with varying trend vegetative crises, apparent persistent bradycardia
      and syndrome of weakness of sinoatrial node. Acute overheating is more commonly
      seen in those miners with as yet little service duration while chronic
      overheating occurs more frequently in those persons with more than 8-year record
      of service in conditions of heating microclimate.

PMID- 9005081
TI  - [The nature of the metastasis in different histological forms of kidney cancer].
AB  - As many as 51 autopsy cards were analysed of those having died of carcinoma of
      the kidney over the period of 1970 to 1992. Lung and lymph gland metastases were
      found to be the most common among different histological forms of carcinoma of
      the kidney, such as clear cell carcinoma, mixed-, granular-, spindle-cell
      variants of renal cell and transitional cell carcinomas. In most cases they were
      of multiple type and were associated with metastases spreading to other organs.
      It was only carcinoma glandulare of hypernephroma and squamous cell carcinoma
      that presented with no lung metastases, which fact may be taken into
      consideration in the diagnosis and prognostication of the medical condition in
      question.

PMID- 9005082
TI  - [The initial experience of using the preparation Ukrain in treating cancer
      patients in Ukraine].
AB  - The chair of general surgery and the chair of oncology of the Ukrainian State
      Medical University have made a study into the use of the preparation "Ukrain" in
      the treatment of oncological patients. Early results of therapy of 23 patients
      confirm the evidence suggesting to us that "Ukrain" is endowed with cancerostatic
      activity, has immunopotentiating effect with no toxicity.

PMID- 9005083
TI  - [The dynamics of the internal radiation activity in schoolchildren living in
      contaminated regions of Zhitomir Province 7 years after the accident at the
      Chernobyl Atomic Electric Power Station[].

PMID- 9005084
TI  - [A rare case of rhabdomyosarcoma of the heart].

PMID- 9005085
TI  - [Cases of primary amebic meningoencephalitis in Kherson Province].

PMID- 9005086
TI  - [The tasks of public health organs concerning the prevention of infectious
      diseases].

PMID- 9005087
TI  - [Scientific management of the work of medical personnel and the improvement in
      manager professionalism in public health].

PMID- 9005088
TI  - [The analysis of expert assessments as a method for the identification and
      forecasting of trends in the development of scientific and medical problems].

PMID- 9005089
TI  - [The developmental concept of a patent information service in Ukraine].

PMID- 9005090
TI  - [The immune status characteristics and kidney function in persons exposed to the
      effect of ionizing radiation].

PMID- 9005091
TI  - [The need for new regulations on the issuing of documents on temporary work
      disability].

PMID- 9005093
TI  - [The characteristics of the diagnostic activities of the physician and
      therapist].

PMID- 9005092
TI  - [The results of an expert evaluation of continuity in the rehabilitation of the
      patients from hospitals and outpatient institutions].

PMID- 9005094
TI  - [The tuberculosis incidence among medical workers in Donetsk Province].

PMID- 9005095
TI  - [The organization of medical care in a secondary boarding school for children
      with diabetes mellitus].

PMID- 9005096
TI  - [The current problems in training military medical personnel for the Armed Forces
      of Ukraine and the measures for their resolution].
AB  - At the time when formation of independent Ukraine and radical reformation of the
      military-medical service take place the demand for competent military medical
      specialists tends to grow, with the range of demand being rather wide in respect
      of paramedical staff as well as that of physicians. One of the efficient ways of
      solving the existing problems is further integration of systems of military
      medical and civilian medical education in the country, to which issue a joint
      sitting of boards of Ministry of Defence and Ministry of Public Health of Ukraine
      was dedicated. With the purpose of improving military medical education in the
      country it is recommended that national Military Medical Academy should be
      established without expanding the permanent staff of the existing organizational
      structures-those dealing with financing, organizational matters, logistics,
      training and instruction-from the numbers it runs to at present.

PMID- 9005097
TI  - [The correction of intravascular microcoagulation of the blood].

PMID- 9005098
TI  - [Levko Ivanovych Medved' (on the 90th anniversary of his birth)].

PMID- 9005099
TI  - [The treatment of postinfarct pulmonary edema: the reserves and potentials].

PMID- 9005100
TI  - [Environmental factors as risk factors for the health of the population: the
      results of epidemiological research and the means for its extension and
      deepening].
AB  - On the basis of the assessment of noncancer risk, main approaches were developed
      and approved to identifying the effects of the environmental factors on the
      health of the population, with special reference to nonspecificity of the action
      of the factors in question, polymorphism of the organism's responses, estimation
      of the threshold of the pollutants actions, specificities of the combined effects
      of environmental factors. The data obtained serve as a basis for identifying the
      extent of risk for exposure of the population to different factors, and it is on
      this foundation that priorities are to be established in designing health
      promotion measures, and the risk is to be correlated with the amounts of the
      necessary measures designed to provide an adequate social protection of the
      population.

PMID- 9005101
TI  - [Hepatoportal hemodynamics in liver cirrhosis with the portal hypertension
      syndrome].

PMID- 9005102
TI  - [Myelodysplastic syndromes: their pathogenesis, diagnosis and differential
      diagnosis].

PMID- 9005103
TI  - [Hemostatic disorders in the pathogenesis of diabetic angiopathy].

PMID- 9005104
TI  - [The chemotherapy of metastases of unknown origin].

PMID- 9005105
TI  - [Autonomic status and neurohumoral regulation in patients with refractory
      tachyarrhythmia].
AB  - Results are submitted of vegetative testing as well as of studying the 24.h
      excretion of catecholamines, activity of cholinesterase, the levels of thyroxin,
      triiodothyronine and hydrocortisone in blood plasma of 120 patients with
      tachyarrhythmias that do not respond to antiarrhythmic drug preparations. The
      functional state of the vegetative nervous system in the attack-free period in
      the above patients was mostly determined by hyperfunction of its sympathetic
      subdivision in the presence of inadequate vegetative reactivity, frequently
      excessive, occasionally weakened, and instability of adrenergic and cholinergic
      influences. It is suggested that augmented secretion of the hormones studied
      might be of compensatory nature.

PMID- 9005106
TI  - [The interrelationship of hemodynamic indices with the phasic structure
      parameters of the left ventricle in hypertension patients].
AB  - Overall one hundred patients with stage II hypertensive disease (HD) were studied
      for central haemodynamics and chronocardiometric estimators of the left ventricle
      (LV) of the heart. Correlation coefficients were calculated between haemodynamic
      indexes and values for (LV) phase structure. In stage II HD, the above
      correlations were found to be dependent upon the type of central haemodynamics.
      But irrespective of the type of blood circulation, there was an inverse
      correlation between the index exertion-time and phase of slow filling, which fact
      is believed to be a compensatory mechanism in cardiac performance under stage II
      HD.

PMID- 9005107
TI  - [The clinico-biochemical, functional, immunological and cellular characteristics
      of the body reactions in patients with the initial stages of hypertension to the
      effect of a magnetic field].
AB  - The article presents a comprehensive evaluation of major clinical, laboratory and
      functional indices in the time course of magnetotherapy as well as during
      administration of such treatments. The most promising alternative appears to be
      that involving the use of immunologic and cellular parameters as markers of
      efficacy of therapeutic action of magnetic fields in early stages of hypertensive
      disease. Causes for effectiveness and ineffectiveness of the above treatment
      option are analyzed, approaches to eliminating those are outlined, the main
      indications and contraindications are determined, merits and demerits of
      magnetotherapy are drawn attention to.

PMID- 9005108
TI  - [The characteristics of the body's functional status and the state of the health
      of pupils in mining trade schools in an industrial zone].
AB  - The article presents results of study into the level of physical development,
      condition of the cardiovascular-, respiratory-, central nervous systems,
      immunobiologic resistance of the organism, prevalence of morphofunctional
      deviations from the norm, and morbidity rates among the students of the mining
      trade secondary school (aged 15-18). It has been found out that adverse
      ecological situation in urban centres of the Donetsk Province together with
      specific character of training for occupation in coal industry have a marked
      negative effect on the functional status as well as health status of the
      adolescents. On the basis of the studies made a complex of measures has been
      designed to maintain and promote the health of students of the mining-trade
      secondary schools.

PMID- 9005109
TI  - [The use of nitrates and slow calcium channel blockers in the treatment of
      patients with ischemic heart disease and disorders of intraventricular
      conduction].
AB  - Data are submitted on the condition of haemodynamics of greater and lesser
      circulation in patients with ischemic heart disease (IHD) presenting with the
      bundle-branch block. On the basis of the results from a combined clinical
      instrumental investigation involving electro- and echocardiography the authors
      present the early objective quantitative criteria for the diagnosis of those
      haemodynamic shifts occurring in formation of the bundle-branch block. The
      blockade of the left bundle of His has a more pronounced effect on the greater
      circulation haemodynamics while that of the right one--on the lesser circulation.
      The authors give a comparative assessment of haemodynamic effects of a single
      dose of isosorbide dindtrate and nifedinin in the patients. Nitrosorbide and
      corinfar improve contractility of the left ventricle, decrease pulmonary
      hypertension and overloading of the right side of the heart.

PMID- 9005110
TI  - [Changes in the indices of left ventricular filling in elderly patients with
      ischemic heart disease].
AB  - With the purpose of examining particular characteristics of filling of the left
      ventricle in elderly IHD patients we evaluated essentially healthy persons, both
      young and of greater age, and elderly IND patients (exertional angina, II-III
      functional class), 20 subjects in each of the three groups of examines, by
      echocardiography followed by the echocardiograms processing on a computer. The
      greatest age-related changes were found for the phase of early filling. Also
      noted in IHD patients was a relatively prolonged atrial systole and shortened
      time of filling, reduction in the value for the index "duration of slow
      filling/duration of fast filling", increase in the volume rate of blood filling
      in the phase of slow filling.

PMID- 9005111
TI  - [The use of accelerating electric stimulation of the left atrium in patients with
      a suspected small-focus myocardial infarct].

PMID- 9005112
TI  - [A comparative analysis of the results of using different methods of helium-neon
      laser therapy in patients with stable stenocardia].
AB  - Based on the findings from the examination of 133 patients with stable angina
      pectoris, it was shown that He-Ne laser therapy with the irradiation being
      applied to the liver projection area in combination with the prolonged-action
      nitrates is superior to similar application of irradiation to the precordial
      region and Head's zones or intravenous irradiation of blood. Revealed in the
      examination of the above patients was a reaction of antiproteolytic enzymes to He
      Ne laser therapy, which appeared to be varying with methods of laser therapy. It
      is suggested that a reaction of the realization of the components of proteolysis
      might be involved in the realization of therapeutic effect of the He-Ne laser
      energy in patients with ischemic heart disease.

PMID- 9005113
TI  - [The level of circulating immune complexes and the microhemodynamic status in
      chronic liver lesions].
AB  - As many as 102 patients with chronic persistent hepatitis and twenty three
      patients with chronic active hepatitis were evaluated for the state of
      microcirculation and levels of circulating immune complexes (CICs). It was found
      out that the degree of microcirculatory disturbances depends upon the type and
      severity of the course of chronic hepatitis. Direct correlation was established
      between the degree of microhemodynamic disorders and levels of CICs, which fact
      indicates the leading role of CICs in the genesis of microcirculatory disorders
      in chronic hepatitis.

PMID- 9005115
TI  - [The moisture-releasing function of the lungs in patients with respiratory organ
      tuberculosis].
AB  - Results are submitted of study into the moisture-releasing function of the lungs
      in healthy persons and patients presenting with various forms of pulmonary
      tuberculosis It has been ascertained that moisture-releasing function is
      changeable and dynamic and depends upon a particular clinical form of
      tuberculosis as well as on the location, and phase in the course of the process.
      A correlation was found between moisture releasing and position being taken up by
      the body.

PMID- 9005114
TI  - [The interaction of the cyclase and immune systems in patients with viral
      hepatitis A and B].

PMID- 9005117
TI  - [The prevalence of disseminated sclerosis in the southern region of Ukraine].
AB  - Some aspects were studied of the occurrence of disseminated sclerosis (DS) in the
      south of Ukraine (Odessa and Nikolaev Provinces) with special reference to
      geoclimatic, ecological and ethnic factors over the period 1992-1993, DS
      incidence was noted to be on the increase in the region, which fact permits
      classifying the South territories of Ukraine as a zone with moderate DS
      prevalence. Data are submitted on nonuniformity of distribution of frequency of
      DS cases on the territory in question. Lineage was traced to the climatic-and
      geographic factors of the region, locality one lives in as well as to sex and
      race.

PMID- 9005116
TI  - [The characteristics of the neurophysiological diagnosis and the main directions
      in the differentiated therapy of brain edema and swelling in patients who are in
      a critical state].
AB  - A total of 186 patients with encephalopathies caused by critical states and
      reanimation were examined. A complex of neurophysiologic studies was proposed
      involving impedancemetry of the brain, rheoencephalography, echoencephalography,
      electroencephalography, ophthalmoscopy. The studies made showed that adoption of
      the proposed complex permits differentiating the processes of edema, swelling,
      edema-swelling of the brain as well as determining the condition of cerebral
      bloodflow and assessing the extent of impairement of cerebral homeostasis. Early
      diagnosis of edema/swelling of the brain enabled the main trends in the
      differential therapy of the above processes to be outlined and adequacy of its
      treatments administration to be effectively controlled on an as-needed basis.
      Differential approach to diagnosis and treatment of edema and swelling of the
      brain permitted the parameters studied to return to normal in 75.2 percent of the
      patients.

PMID- 9005118
TI  - [A model of the levels of functioning for psychiatric medicosocial expertise].
AB  - Based on the examination of 302 schizophrenic patients there have been
      established criteria for assessment of social functioning of mental patients. The
      clinical model holds nine levels of functioning. Assessment criteria will, we
      believe, help in bringing off unanimity as to definition of levels of social
      functioning, developing programmes of rehabilitation of disabled persons tailored
      to the individual, assessing the efficiency of exposure to medical-rehabilitative
      treatments over time.

PMID- 9005120
TI  - [Imaging methods, particularly magnetic resonance, in multiple sclerosis].
AB  - Multiple sclerosis (MS) can only be diagnosed with a certain probability. There
      are neither any specific moments in the medical history of the patient, nor
      clinical or paraclinical tests as well as their combinations that would prove the
      diagnosis. In the daily routine the most common criteria we use are of
      Schumacher, Poser and Bartel. Until the magnetic resonance imaging (MRI) had been
      introduced into the clinical practice, imaging methods were used to exclude other
      treatable lesions (e.g. tumors, arteriovenous malformations etc.), even though
      computerized tomography (CT) successfully demonstrated some of the plaques. In
      the MS CT is both insufficiently sensitive as well as specific. On the contrary
      MRI is in the MS highly sensitive, 92-98% specificity has been achieved among
      clinical definite cases. MR is nowadays a method of choice for not only the
      diagnosis but also for the further follow up of our MS patients. Multiple focal
      hyperintense lesions on T2 weighted images (T2WI) or the flow attenuated
      inversion recovery imaging mode (FLAIR) are the typical pathological findings.

PMID- 9005119
TI  - [A new sorbent for the treatment of intestinal infections].
AB  - A new inorganic sorbent is proposed endowed with high adsorption-chemical
      activity towards microorganisms. Animal studies showed that the preparation
      "Evirhip" is superior to coal-based sorbents (KAY and CKN) and polymethilsiloxan
      (PMS) towards pathogenic microorganisms, PMS having relatively higher adhesive
      activity towards Salmonellas than coal-based sorbents.

PMID- 9005121
TI  - [Relation between socioeconomic factors and mortality in districts in the Czech
      Republic 1989-1993].
AB  - BACKGROUND: Socioeconomic factors have been identified as important determinants
      of morbidity and mortality in many populations but only few studies examined
      their importance in the Czech population. The objective of this study was to
      analyse the relationship between socioeconomic characteristics and mortality in
      districts of the Czech Republic in 1989-1993. METHODS AND RESULTS: The
      association between age-standardised mortality (for men and women separately)
      from all causes, all cancers, lung cancer, cardiovascular and ischaemic heart
      disease in the age group 35-64 and socioeconomic characteristics of districts
      reported from the 1991 Census was studied in multiple linear regression. In
      principle, associations between socioeconomic factors and mortality were similar
      for all causes of death. Mortality was inversely related to percentage of
      population with secondary and university education and to proportion of
      population with any religious denomination. After controlling for other factors,
      correlation coefficients (r) between all cause mortality and proportion of
      population with primary education were 0.69 in men and 0.64 in women; for the
      proportion of population with any religious denomination the r were -0.42 and 
      0.72, respectively. Relation of mortality to mean of persons per room was
      stronger in women (r = 0.29) than in men (r = 0.10). Population density was most
      closely correlated with ischemic heart disease (r = 0.41) in men and 0.43 in
      women). Available socioeconomic factors explained over 60% of geographical
      variation in mortality from all causes, more than 50% of variation in cancers and
      about 40% of variation in ischaemic heart disease. CONCLUSIONS: Although
      ecological studies do not allow firm identification of causal factors, our
      results agree well with other studies, and confirm the important effect of
      socioeconomic factors on health in the Czech population.

PMID- 9005122
TI  - [Treatment of duodenal ulcer with pantoprazole. A multicenter study].
AB  - BACKGROUND: The inhibition of H+/K(+)-ATPase (proton pump) of gastric parietal
      cells by substituted benzimidazoles represents a new therapeutic approach in
      conditions connected with hypersecretion of hydrochloric acid. Pantoprazol is the
      newest member of this group of drugs. Monotherapy of duodenal ulcer with
      pantoprazole or ranitidine was evaluated in terms of healing rate, tolerance and
      compliance. METHODS AND RESULTS: A double-blind, parallel-group comparing study
      (double dummy technique) of treatment florid duodenal ulcer (diameter 5-20 mm)
      was performed in 95 subjects (age 18-74 years). The active substances were either
      pantoprazole (40 mg before breakfast-47 subjects) or ranitidine (300 mg before
      bedtime-48 subjects). The average diameter of the ulcer and subjective complaints
      before treatment were comparable in both groups. After 2 weeks of pantoprazole
      therapy 88.5% of ulcers (a) and 87.2% patients (b) were cured, whereas the
      corresponding values in the ranitidine series amounted to 66% (a) and 62.5% (b)
      only (p = 0.006 for both (a) and (b)). The rate of healing in relative values of
      reducing the ulcer size was significantly higher after 2 weeks of pantoprazole
      therapy (p = 0.026 (a) and 0.0027 (b)). All ulcers healed after 4 weeks of this
      regimen. The difference between the pantoprazole and ranitidine series after 4
      weeks was closely above the 5% level of significance (p = 0.589 for (a) and
      0.0588 for (b) respectively). This was due to the low number of patients in both
      groups at this time interval, particularly in the pantoprazole group. Pain during
      day-time and regurgitation were observed significantly more frequently after
      ranitidine therapy. The compliance was very good and practically no adverse
      effects of pantoprazole therapy were observed. CONCLUSIONS: The healing rate of
      duodenal ulcer with pantoprazole monotherapy (40 mg before breakfast) was
      significantly higher than with ranitidine (300 mg before bedtime). The compliance
      of patients and the tolerance of pantoprazole were very good and its
      administration was not associated with any side-effects.

PMID- 9005123
TI  - [A method for detection of germinal mutations in the p53 tumor suppressor gene].
AB  - BACKGROUND: The tumour suppressor gene p53 is exhibits somatic mutations in a
      high proportion of human tumours. In addition, there are cancer families
      suffering from the Li-Fraumeni syndrome, the members of which carry germ line
      mutations in this gene. The carriers of the p53 germ line mutations have a high
      risk of developing tumours. The genetic diagnosis of carriership of the mutation
      in the tumour family members is important for preventive measures and for
      eventual tumour therapy modification. METHODS AND RESULTS: We have developed a
      method for the detection of germ line mutations in the p53 gene based on non
      radioactive SSCP and direct sequencing of PCR products. We have proved the
      efficiency of the method by finding known mutations in eight tumour cell lines.
      In our collection of tumour families we have detected polymorphisms in exons 4
      and 6 of the p53 gene. In one family which conformed to the criteria of the Li
      Fraumem syndrome we have found a novel germ line mutation in exon 5. CONCLUSIONS:
      The method developed by us is very simple and sensitive. The germ line mutations
      in the p53 gene are very rare.

PMID- 9005124
TI  - [Immunologic profile of patients with a transplanted kidney in the postoperative
      period].
AB  - In our study we follow up a response of specific and a part of nonspecific
      cellular immunity in recipient organism with renal transplantation of cadaveric
      kidney to a standard immunosuppressive treatment used in the Department of
      Urology in Faculty hospital in Hradec Kralove.

PMID- 9005125
TI  - [20th anniversary of the opening of the new Urologic Clinic facility at Charles
      University Medical School in Prague].

PMID- 9005126
TI  - [Surgery of the breast: 100 years after Halsted].
AB  - In the early years of this century prevailing currents of medical opinion led to
      the imposition of surgery that was even more aggressive than the radical
      mastectomy proposed by Halsted to treat breast cancer. More recently breast
      conservation surgery has become established but is always accompanied by
      additional local treatment and often the option of systemic therapy. Studies
      conducted in Milan were the first to demonstrate that conservative surgery plus
      and adjuvant therapy such as radiotherapy is efficacious in treating small-size
      breast cancer. As the year 2000 approaches it has become clear that breast cancer
      is curable in a high proportion of cases and attention is turning to improving
      the aesthetic outcome of surgery, and to investigating biological and genetic
      factors that influence the disease.

PMID- 9005127
TI  - [Role of biological indicators in the therapeutic decision in breast carcinoma].
AB  - Before planning therapeutic strategies for patients at different risks of
      relapse, it is essential to identify prognostic factors. In addition to important
      anatomo-pathological prognostic factors such as lymph node status and tumour
      size, certain biological indicators, such as receptor status and proliferative
      kinetics, are now regarded as useful tools for prognosis. Tumour cell kinetics is
      an important prognostic variable in different stages of breast cancer. It is also
      a useful index for identifying subjects of aggressive tumours in node-negative
      patients. As far as the relationship between TLI estrogen receptor status and
      tumor size is concerned, it has been observed that only TLI retains its
      prognostic significance as regards both time to relapse and overall survival.
      Lymph node status, receptor status, cell kinetics and c-erbB-2 expression were
      examined as predictive factors of response. It emerged that not all
      chemotherapeutic regimens have the same impact in a situation where the disease
      is evaluated exclusively on the basis of lymph node status. Moreover, receptor
      status and receptor level significantly condition the response to endocrine
      therapy. Response rates to chemotherapy increase in highly proliferating tumours,
      whereas endocrine therapy achieves a better response in ER+ tumours with a low
      TLI index. Further studies are needed to clarify the role of c-erbB-2 as a
      predictive factor of response.

PMID- 9005128
TI  - [Role of axillary dissection in breast carcinoma].
AB  - Between 1986 and 1995, 965 patients with T1 breast cancer were treated with wide
      excision (796 pts) or mastectomy (138 pts). Axillary dissection was performed in
      934 patients. Nodal positivity was 8.7% for T1a, 15.6% for T1b and 37.7% for T1c.
      68.5% of cases had one to three positive nodes, 18.3% four to ten and 13% more
      than ten nodes. No differences were observed in the frequency of lymph nodes
      involved according to the age of patients, menopausal status, pattern at
      mammography, histology and receptor status. Favourable histology (tubular,
      cribriform, papillary, colloid) shows a significant difference when compared with
      all the others histotypes. On the basis of data collected it is impossible to
      anticipate the axillary status and avoid axillary dissection.

PMID- 9005129
TI  - [Femoro-femoral crossover bypass in monolateral obstructions of the iliac
      artery].
AB  - The Authors report the result of their ten-years experience with femoro-femoral
      crossover bypass in 26 patients affected with unilateral occlusion of the iliac
      artery. This bypass is an easy and quick procedure, useful in both short and long
      term. The patency rate after 58 months is 84.6%. Thus, its use indicated in a
      high number of patients, not only for a limb salvage treatment of a disabling
      claudication. The indications for this bypass can be extended to low surgical
      risk subjects, and it does not have to be considered only for the high-risk
      patients, instead of major surgery procedure on the aorto-iliac axis. The minimal
      necessary conditions of the limbs for performing the femoro-femoral crossover
      bypass are a pressure gradient of 35 mmHg and the angiographical demonstration of
      the unilateral occlusion. If the contralateral axis appears patent, but there are
      also multiple atherosclerotic sites, we consider other bypasses as therapeutical
      choices: aorto-bifemoral, ilio-femoral and the femoro-femoral cross-over itself;
      in the latter case we previously perform a transluminal angioplasty or an
      endarterectomy of the donor iliac artery. In these situations is essential to
      evaluate of the benefit/risk rate for every single patient.

PMID- 9005130
TI  - [Complications of thyroidectomy: hemorrhage].
AB  - The authors report their experience in haemorrhage after thyroid surgery.
      Haemorrhagic complications occurred in 5 cases in a series of 1803 sequential
      thyroidectomies (incidence: 0.27%). In particular, incidence was 1.9% after
      interventions for thyroid neoplasias (adenoma and carcinoma) and 0.18% after
      interventions for non-neoplastic thyroid pathology. Haemorrhage occurred always
      after "total" operations, even if monolateral. Causative and contributing
      factors, precautions and measures helpful in reducing the incidence and the
      potential dangerousness of haemorrhagic complications are discussed.

PMID- 9005131
TI  - [Hepatobiliopancreatic surgery in patients over 70 years old: which anesthesia?].
AB  - In the last years the criteria of operability have been extended to elderly
      patients with hepato-pancreatic-biliary diseases. We selected 46 patients (in the
      seventies or older, class 3 or 4 of ASA score, affected by hepato-pancreatic
      biliary neoplasms) in order to evaluate the behavior of these patients undergoing
      to different anaesthesiological techniques. Randomly, we treated 24 patients
      (group A) in general anaesthesia, and 22 patients (group B) in peridural
      anaesthesia. We considered mortality rate, morbidity rate, as sepsis, wound
      infection, pleuritis, and pneumonias. The data were analyzed by chi2-test and
      Fisher's exact test (p < 0.05). Mortality rate was similar in the two groups (A =
      4.1, B = 4.5) (p = ns), and no complications were determined by the different
      anesthesiologic procedures. Pleuritis was present in 44% of group A vs 45% of
      group B (p = ns). Atelectasis areas were present in 58% of group A vs 27% of
      group B (p = ns), pneumonia was present in 33% of group A vs 9% of group B: this
      value was significant (p = 0.049). There were no differences between the two
      groups regarding wound infection rate (only one case in group B). We think that
      pulmonary diseases can be determined by intubation and mechanical ventilation. We
      show a significant reduction of pneumonia in the patients that underwent
      peridural anaesthesia. For this reason, peridural technique can be safely
      extended to elderly patients with hepato-pancreatic-biliary diseases.

PMID- 9005132
TI  - [Fetal surgery: state of the art].
AB  - After a major search of the more recent literature, the Authors present a
      critical examination of guidelines now in use for the surgical treatment in utero
      of numerous fetal abnormalities. Specifically, they underline not only ethical
      and deontological but also technical principles relating to this particular
      surgery. They are also involved in examining the depth all the more common
      surgical procedures used in different pathologies and in suggesting new lines of
      future development.

PMID- 9005133
TI  - [Diagnostic framework of nonpalpable lesions of the breast].
AB  - Mammography is the most sensitive test for non-palpable lesions, but its
      specificity is quite limited. When a decision for biopsy is based only on the
      mammographic appearance the benign/malignant biopsy ratio (B/M) is around 3:1.
      The B/M varies according to the radiological pattern being favourable for
      stellate opacities, high for regular opacities, and intermediate for distortions
      and microcalcifications. Aspiration cytology of non-palpable lesions, either
      sonographically or stereotaxically guided, is highly accurate. When the decision
      for surgical biopsy is taken also on the basis of cytology, B/M may be reduced by
      up to 0.5:1. As false negatives are expected for cytology, lesions which are
      strongly suspicious at mammography must be biopsied anyway. Sonography guided
      aspiration is possible in about a half of mammographically detected non-palpable
      lesions, particularly for opacities, whereas distortions and microcalcification
      are seldom visualized at sonography. Cytology should be routinely performed in
      the presence of questionable non-palpable lesions.

PMID- 9005134
TI  - [The Shouldice plastic surgery: our clinical experience].
AB  - The Authors present cases of groin hernioplasty using the Shouldice method; the
      method used for more than six years, such as elective technique to treat groin
      hernia, is evaluated on the basis of results of complications and recurrences. A
      careful clinical check of patients operated on over one year at least, allows
      confirmation of the efficiency of the method, because it results in a low
      percentage of recurrence and complications, plus a low social and economical
      cost. For these reasons it is proposed that the method is applied in day surgery.

PMID- 9005135
TI  - [Intraoperative histological study of nonpalpable lesions of the breast].
AB  - The intraoperative frozen section technique has proven to be valid and accurate
      in the diagnosis of palpable breast lesions, while its use in non-palpable
      lesions of the breast has been recently discussed. In order to estimate the
      accuracy of frozen section technique in non-palpable breast lesions we reviewed
      our series of 672 cases of non-palpable lesions examined intraoperatively between
      January 1977 and December 1991. Frozen section diagnoses were compared with
      diagnoses obtained at review of the permanent paraffin sections. A review of the
      mammographic pattern of each lesion was also carried out. Frozen section
      diagnosis was replaced by permanent paraffin sections in 22 cases (3.3%). Benign
      or malignant (in situ and invasive carcinomas) frozen section diagnoses were
      accurate in 623 of 650 cases (95.8%). Frozen section diagnosis was modified on
      the basis of permanent sections in 27 cases (4.2%), with 3 false positives and 24
      false negatives. Sensitivity and specificity of frozen section technique were
      91.7% and 99.2%, respectively. Comparing frozen section and definitive diagnosis
      according to the mammographic pattern, sensitivity was lower in patients with
      microcalcifications as the only alteration (88.8%) compared with patients with
      opacities (94.9%). On the basis of our results the frozen section technique in
      non-palpable breast lesions is to be considered a valid and reliable diagnostic
      procedure, particularly in lesions detectable at mammography as an opacity and
      identifiable on gross examination of the surgical specimen.

PMID- 9005136
TI  - Of no significant benefit.

PMID- 9005137
TI  - European system for reporting adverse reactions to and defects in
      radiopharmaceuticals: annual report 1995.

PMID- 9005138
TI  - The benefits of participation in clinical trials.
AB  - This editorial marks a change of editors for the trials section. It is intended
      to encourage surgeons to participate in clinical trials work. The recruitment of
      patients into clinical trials with strict protocols and quality control may be
      expected to lead to better outcomes. Well-conducted trials may also add to our
      understanding of tumour biology and the role of prognostic markers, and may lead
      to the standardization of definitions and medical terminology. This will help us
      to overcome uncertainties in current treatment protocols.

PMID- 9005139
TI  - http://www.hbuk.co.uk--the European Journal of Surgical Oncology and the
      Internet.
AB  - The popularization of the Internet through the World Wide Web heralds a new era
      in public and professional communication. The European Journal of Surgical
      Oncology is now represented on the Web at a site provided, developed and
      maintained by the publisher. We may expect to see rapid developments in
      electronic publishing, although the direction and general utility of these
      changes are not yet clear. This article introduces the EJSO Web site to the
      readership and considers the ways in which the Internet Revolution may bring
      benefits to the readership, the publisher, the editorial process and the Journal
      staff.

PMID- 9005140
TI  - Axillary node clearance: who wants to immobilize the shoulder?
AB  - Sixty-seven patients undergoing level three axillary node clearance were studied
      to ascertain the benefit of collar and cuff shoulder immobilization in reducing
      the incidence of axillary seroma formation. During this period the patients'
      views were obtained on this aspect of post-operative care. Although daily
      drainage volume decreased more rapidly in those patients whose shoulders were
      immobilized this did not result in a significant decrease in seroma formation
      following drain removal on the fifth post-operative day (31% vs 43%, P>0.05).
      Patient interviews revealed that they found the collar and cuff incapacitating,
      felt it delayed their return to normal activity and made personal hygiene
      difficult to maintain. In view of these results shoulder immobilization should
      not be employed in the routine post-operative care of these patients.

PMID- 9005141
TI  - Argon-enhanced cutting and coagulation confers advantages over conventional
      electrocautery for mastectomy.
AB  - In this prospective randomized study we have compared argon-enhanced
      electrosurgery with conventional diathermy in a consecutive series of 50 patients
      undergoing mastectomy. The groups were comparable in age, menopausal status,
      tumour size, stage and specimen size. Patients undergoing mastectomy using argon
      diathermy had significantly less blood loss intraoperatively (521 (67)ml vs 824
      (59)ml; P<0.001) and a significantly lower transfusion requirement post
      operatively. There were no significant differences in post-operative drainage
      (1350 (160) ml vs 1527 (169) ml; P=NS), length of hospital stay, incidence of
      seromas or other complications. Argon diathermy significantly reduces
      intraoperative blood loss and should be considered as the method of choice in
      patients undergoing mastectomy.

PMID- 9005142
TI  - DNA fingerprinting of benign and malignant breast lesions.
AB  - Paired blood and breast tissue samples from 96 patients undergoing surgical
      excision of a breast lesion were subjected to DNA fingerprint analysis using the
      minisatellite probes 33.6 and 33.15. The 'fingerprints' of the blood and breast
      DNA were compared. DNA fingerprint changes seen were classified as band
      additions, band deletions or changes in band intensity. Significantly more DNA
      fingerprint changes were seen in malignant than in benign lesions (probe 33.6,
      P<0.01; probe 33.15, P=0.01; both probes, P = 0.04). The frequency of the changes
      detected in the breast cancers was unrelated to tumour grade or the presence of
      invasion. DNA ploidy was measured in 70 of the breast carcinomas. DNA fingerprint
      changes were seen in 41 of these, but flow cytometry detected aneuploidy in only
      29 tumours (P=0.04). The DNA fingerprinting technique is unlikely to be useful in
      differentiating between benign and malignant breast lesions as changes were
      detected in one of the fibroadenomas studied. However, it may be a useful
      technique in screening tumour DNA for abnormalities suitable for more detailed
      analysis.

PMID- 9005143
TI  - Immunohistochemical detection of oestrogen receptors in ductal carcinoma in situ
      of the breast.
AB  - The expression of oestrogen receptor (ER) protein in invasive carcinoma of the
      breast and its clinical significance has been extensively evaluated. Little
      information is available regarding ER expression in ductal carcinoma in situ
      (DCIS). In this study, 46 formalin-fixed, paraffin-embedded tissue specimens of
      mammographically detected DCIS were evaluated immunohistochemically for the
      presence of ER using specific monoclonal antibodies against ER (ER-ICA Abbott
      Lab). The associations between ER expression and histological type, degree of
      differentiation and patient menopausal status were evaluated. Positive ER
      staining was present in 72% of cases. Non-comedo types of DCIS were more
      frequently ER-positive than comedocarcinoma. ER-positive tumours were inversely
      correlated with the presence of nuclear pleomorphism. The incidence of ER in pre
      menopausal and post-menopausal women was similar. In conclusion, ER expression is
      present in a considerable percentage of DCIS, and ER-positivity is associated
      with the degree of differentiation and non-comedo carcinoma variants.

PMID- 9005144
TI  - Protective effect of leuprolide acetate on 7,12-dimethylbenz(a)anthracene (DMBA)
      induced mammary carcinogenesis in rats.
AB  - The anti-carcinogenic effect of TAP-144-SR biodegradable microcapsules of copoly
      (DL-lactic/glycolic acid) copolymer containing a potent LHRH agonist, TAP-144 (D
      Leu6-(des-Gly10-NH2)-LHRH ethylamide, leuprolide acetate) was investigated in
      7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumours. At 50 days of
      age, all rats were given 20 mg doses of DMBA by gastric intubation. Rats on the
      Initiation Group were given a single s.c. injection of TAP-144-SR (3 mg/kg) 1
      week before DMBA treatment, and rats in the Promotion Group were given repeated
      s.c. injections every fourth week from 1 week after DMBA treatment until the end
      of the experiment. In the Initiation Group, tumour incidence and multiplicity
      were reduced to 20.8% and 15.0% of the Control Group values, respectively. In the
      Promotion Group, tumour incidence and multiplicity were also reduced to 17.7% and
      7.9%, respectively. It was suggested that TAP-144-SR may be a potential candidate
      as an agent for hormonal chemoprevention in breast cancer.

PMID- 9005145
TI  - Medullary thyroid cancer: the role of radiotherapy in local control.
AB  - Fifty-one patients were treated with radiotherapy for loco-regional medullary
      thyroid cancer between 1960-1992. The actuarial overall survival at 5, 10 and 20
      years was 69%, 52% and 30%, respectively. Patients were classified according to
      clinical stage (node-positive or -negative), post-operative histological residual
      disease status (none, microscopic or macroscopic) and dose of radiotherapy
      received. By univariate analysis, loco-regional recurrence-free survival was
      significantly longer for node-negative patients (P = 0.03). Patients who received
      at least 60 Gy over 6 weeks showed a trend towards improved local control (P =
      0.23). The only significant variable by multivariate analysis for local
      recurrence-free survival was post-operative residual disease status (P=0.0005).
      The local control rate at 5 years was 100% for patients with no residual disease,
      65% for those with microscopic tumour, and 24% for those with macroscopic
      residual disease. We conclude that there is a valuable role for radiotherapy in
      the management of patients with residual microscopic or macroscopic disease
      following surgery, as well as in those with inoperable disease.

PMID- 9005146
TI  - Colorectal cancer--a multivariate analysis of prognostic factors.
AB  - The data from 1050 patients who had undergone colorectal carcinoma resection at
      the University of Cologne between 1976 and 1990 were studied. The aim of the
      study was to determine the concomitant effects on survival of several patient
      characteristics (sex, age, tumour localization, blood transfusion) and
      histopathological variables (Dukes' staging). We first calculated survival rates,
      both including and excluding post-operative mortality. We set up a hierarchical
      log-linear model for the detection of relationships between selected
      crossclassified categorial variables. We then used Cox's proportional hazard
      regression method to study the relationship between survival and different
      prognostic patterns. Dukes' staging was shown to be a highly discriminating
      factor in survival (P<0.001). Survival rates were better in women (P<0.001), and
      better for younger patients (<70 years; P<0.001). Tumour site (colon; P = 0.0362)
      and blood transfusion (P = 0.0857) also correlated with survival.

PMID- 9005147
TI  - Anorectal melanoma in The Netherlands: a report of 63 patients.
AB  - A retrospective analysis was performed of the clinical features and results of
      surgical treatment modalities of 63 cases of anorectal melanoma collected in The
      Netherlands. Most tumours presented in an advanced stage due to the obscure
      location and lack of specific symptoms. There were 34 patients with clinical
      stage I disease who were treated by either local sphincter-saving surgery (n=16)
      or who had undergone an abdominoperineal resection (APR) (n=18). We could not
      find a survival advantage for either one of these two treatment modalities.
      However, after a local procedure far more local recurrences were seen (12:1), but
      this did not influence the clinical course of these patients, as they often
      rapidly succumbed to distant metastases. It is concluded that, in the future,
      patients presenting with an anorectal melanoma should be treated with a sphincter
      saving surgical approach whenever possible.

PMID- 9005148
TI  - A new laparoscopic abdominal radical hysterectomy: a pilot phase trial.
AB  - The video laparoscopy, hydrodissection and laparoscopic scissors were used to
      develop adequate tissue planes in avascular pelvic areas. Haemostasis was
      accomplished by the laparoscopic suturing method and tying an extracorporeal
      sliding knot, enhanced by an intracorporeal two-turn flat square knot. Six
      patients with cervical carcinoma stage I B or II A were subjected to laparoscopic
      para-aortic, external iliac, obturator fosea, and hypogastric node dissection,
      followed by laparoscopic radical abdominal hysterectomy. The outcome of this
      pilot phase trial indicated that this operation can be executed laparoscopically
      with no transvaginal surgery. The integrity and principles of classic
      transabdominal radical hysterectomy with extended pelvic lymphadenectomy were
      honoured. Using the surgical technique of laparoscopic abdominal radical
      hysterectomy with extended pelvic lymphadenectomy eliminates laparotomy morbidity
      itself. This operation encouraged rapid post-surgical recovery, shortened
      recuperation time, and minimized post-operative discomfort.

PMID- 9005149
TI  - Pre-operative plasma levels of C-reactive protein, albumin and various plasma
      protease inhibitors for the pre-operative assessment of operability and
      recurrence in cancer surgery.
AB  - Pre-operative levels of the acute phase protein C-reactive protein (CRP), albumin
      (assessing nutritional status), the tumour marker CEA and three plasma protease
      inhibitors, i.e. C1-esterase inhibitor, alpha-2-macroglobulin and antithrombin
      III, were prospectively studied in 183 patients with various solid cancers.
      First, the predictive value of abnormal levels for operability at the primary
      operation was studied. Secondly, the predictive value of abnormal levels for
      cancer recurrence and metastases was evaluated during 2 years of follow-up. The
      results show that malignancy induces increased CRP and C1-esterase inhibitor
      levels and decreased albumin levels in serum. These changes, as well as raised
      alkaline phosphatase and lowered haemoglobin levels, also correlate to the
      'overall' tumour burden. The most important conclusion is, that increased pre
      operative CRP levels (CRP > or = 10 mg/l; sensitivity, 79%; specificity, 71%)
      and/or low albumin levels (albumin <37 g/l; sensitivity, 94%; specificity, 54%)
      are seen in inoperable cancer patients compared with patients having operable
      cancers. The second main important conclusion is, that high pre-operative C1
      esterase inhibitor levels (C1-esterase inhibitor >152%; sensitivity, 45%;
      specificity, 90%), and in some patients a high alkaline phosphatase level, are
      seen in patients exhibiting early cancer recurrence (within 2 years post
      operatively).

PMID- 9005150
TI  - Is the binding of the lectin Helix pomatia agglutinin (HPA) of prognostic
      relevance in tumours of the upper aerodigestive tract?
AB  - The lectin Helix pomatia agglutinin (HPA) has been used as a prognostic indicator
      in a number of clinical studies including those of breast, colorectal and gastric
      cancer. Binding of HPA to tissue sections was associated with a bad prognosis
      indicating that the carbohydrate residue recognized by this lectin is linked to
      metastasis. In order to investigate whether HPA binding is also of prognostic
      relevance in squamous cell carcinomas of the upper aerodigestive tract, 53
      tumours of this region were stained with HPA. Almost all tumours (95%) bound HPA
      to various degrees and hence HPA binding is of no prognostic relevance in this
      group of tumours. These findings indicate a fundamental difference in the role of
      carbohydrate residues in metastasis between squamous cell carcinoma (as in our
      study) and in tumours derived from glandular tissues such as breast, colon and
      stomach.

PMID- 9005151
TI  - Treatment of pathological fractures of the humeral shaft due to bone metastases:
      a comparison of intramedullary locking nail and plate osteosynthesis with
      adjunctive bone cement.
AB  - In a retrospective study 37 patients were surgically treated for 38 fractures (27
      actual and 11 impending) caused by metastatic lesions of the humerus shaft. A
      comparison between plate osteosynthesis with bone cement (20 cases) and
      intramedullary nailing (18 cases) was made. There was no mortality related to the
      surgical procedure. The patients' survival rate was 61% after 3 months and 44%
      after 6 months; six were alive after 1 year. Overall, a subjective and objective
      relief of pain was achieved in 92% and 79%, respectively. Restoration of arm
      function was improved in 95%. The operative course was complicated in six
      patients after plate osteosynthesis (three local and three systemic
      complications) and in four patients after intramedullary nailing (one local and
      three systemic complications). Fixation failed in four patients, instability
      developed twice after intramedullary fixation without bipolar static locking. No
      significant difference in survival rate, pain relief, restoration of function and
      complications were associated with methods of treatment, or with operation of
      actual or impending pathological fractures. Despite the poor life expectancy our
      results indicate that intramedullary nailing with bipolar static locking and post
      operative irradiation or plate osteosynthesis with bone cement for treatment of
      pathological (impending) fractures of the humerus shaft are safe ways to restore
      arm function and improve quality of life.

PMID- 9005152
TI  - Steroid hormones and cancer: (I) basic biology and endocrinology.

PMID- 9005153
TI  - The case for high-dose adjuvant chemotherapy in breast cancer: (II) clinical
      experience.
AB  - Recent Phase II studies on the use of myelo-ablative chemotherapy in breast
      cancer have confirmed that this approach is associated with low mortality and
      apparent efficacy. In a preceding article the theoretical arguments were
      presented for testing this approach in the high-risk adjuvant setting; in the
      current article the clinical data justifying the present approaches for this type
      of treatment are reviewed. The evidence suggests that peripheral blood stem cell
      supported myelo-ablative chemotherapy should be tested against conventional
      regimens in order to determine whether or not the increased expense and toxicity
      of such an approach is associated with improved survival for women whose axillary
      node status places them at high risk of disease relapse and subsequent death.

PMID- 9005154
TI  - Subpleural haematoma presenting as a 'pseudotumour' following fine-needle
      aspiration biopsy of the breast.

PMID- 9005155
TI  - Failed treatment of pseudomyxoma peritonei (PMP) with intraperitoneal interferon
      alpha.

PMID- 9005156
TI  - Metastatic renal adenocarcinoma presenting in a breast screening programme.

PMID- 9005157
TI  - [Comparison of outcome of primary PTCA for acute myocardial infarction in
      patients younger and older than 70 years of age].
AB  - BACKGROUND: The Primary Angioplasty in Myocardial infarction Study Group reported
      that the benefit of primary PTCA was observed mainly among patients who were
      classified as "not low risk" including those over age 70, with anterior
      infarction and heart rate > 100 bpm. The present study compares procedural
      success rate and in-hospital and one-month clinical outcome of primary PTCA in
      acute myocardial infarction patients < 70 and > or = 70 years of age. METHODS AND
      RESULTS: During 1995 121 patients with acute myocardial infarction underwent
      primary PTCA within 6 hours of symptoms onset or within 24 hours in case of
      evidence of ongoing ischemia. Eighty-two patients (Group I) were < 70 (mean age
      56 +/- 9) and 39 patients (Group II) were > or = 70 (mean age 75 +/- 3). In group
      II there was a trend, although not significant, toward a higher prevalence of
      prior angina and infarction. Multivessel disease was more frequent in group II
      than in group I (69% vs 48%; p = 0.041). Ejection fraction was markedly depressed
      in both groups (38 +/- 10% in group I vs 34 +/- 11% in group II). Ejection
      fraction < or = 30% and shock on admission were more frequent in group II (39% vs
      15% and 36% vs 21%, respectively). Optimal angiographic success (< or = 30%
      stenosis associated with TIMI grade 3 flow) was achieved in 77% of group II and
      in 98% of group I (p = 0.00059). The in-hospital mortality rate was 26% in group
      II and 1.2% in group I (p = 0.000042). Shock on admission and PTCA failure
      predicted high mortality rates. There was no difference between the two groups as
      regards to non-fatal reinfarction, recurrent ischemia, life-threatening
      arrhythmias, severe heart failure, revascularization procedures. There were no
      strokes. At one-month follow-up, recurrence of ischemia or positive response to
      stress test were more frequent in group II (24% vs 8%; p = 0.039). CONCLUSIONS:
      In patients with acute myocardial infarction < 70 years of age primary coronary
      angioplasty is associated with low rates of mortality and cardiac events.
      Mortality rate remains high in patients over age 70, especially when shock is
      present on admission or PTCA falls.

PMID- 9005158
TI  - [Pulmonary venous flow in patients with chronic heart failure: feasibility and
      additional value compared to transmitral flow for non-invasive estimation of
      pulmonary wedge pressure].
AB  - BACKGROUND: In many cardiac conditions, Doppler of transmitral flow has been
      showed to be related to left ventricular filling pressure, but several factors
      may limit its practical value in estimating pulmonary wedge pressure in patients
      with chronic heart failure. Pulmonary venous velocities directly depend on the
      oscillations of left atrial pressure. Recent studies suggest that transthoracic
      Doppler of pulmonary venous flow provides a more accurate estimation of pulmonary
      wedge pressure. However the relative values of transmitral and pulmonary venous
      flow for assessing pulmonary wedge pressure in patients with chronic heart
      failure have not been fully classified until now. Accordingly, we performed this
      study to assess the feasibility of transthoracic Doppler of pulmonary venous flow
      in patients with chronic heart failure and to evaluate whether it provides
      additional information regarding pulmonary wedge pressure when compared with
      Doppler indices of transmitral flow. METHODS: Simultaneous Doppler
      echocardiographic examinations and right heart catheterizations were performed
      prospectively in 300 consecutive patients with chronic heart failure due to
      dilated cardiomyopathy. The correlations of mitral and pulmonary venous flow
      velocity variables, left atrial volumes, mitral regurgitation jet area and left
      ventricular ejection fraction with pulmonary artery wedge pressure were
      evaluated. RESULTS: A complete recording of transthoracic pulmonary venous flow
      including all components was obtained in 66% of patients, while only systolic and
      diastolic forward flow were recorded in 88% of patients. Several indices, derived
      from pulmonary venous flow, were correlated with pulmonary wedge pressure; the
      strongest correlation was between systolic fraction of peak velocities and
      pulmonary wedge pressure (r = -0.76). This value was similar to that obtained
      between deceleration rate (r = 0.78) and deceleration time (r = -0.67) of
      transmitral flow and pulmonary wedge pressure. A systolic fraction > 40% showed a
      greater positive predictive value than restrictive pattern of transmitral flow
      for identifying patients with pulmonary wedge pressure > 18 mmHg (95% vs 86% p <
      0.05). This accuracy is confirmed also in patients who had a single peak of
      transmitral flow. CONCLUSIONS: Doppler of pulmonary venous flow can be performed
      in a high percentage of patients with chronic heart failure due to dilated
      cardiomyopathy. The indices derived from transthoracic pulmonary venous flow are
      strongly correlated with pulmonary wedge pressure and improve the noninvasive
      identification of patients with high pulmonary wedge pressure, even when
      transmitral flow pattern is difficult to be interpreted.

PMID- 9005159
TI  - [Surgical treatment of ischemic heart disease complicated with severe left
      ventricular dysfunction: experience in 200 cases].
AB  - BACKGROUND: The study was designed to evaluate short and long-term benefits of
      coronary artery bypass graft in patients with coronary artery disease and
      severely depressed left ventricular ejection fraction and to identify
      contemporary risk factors associated with significantly greater mortality in this
      high-risk subgroup. METHODS: From 1985 to 1995, 200 consecutive pts with EF < or
      = 0.30 underwent CABG. Among these patients, 60% were older than 70 years. NYHA
      functional class III/IV was present in 31% of pts. Preoperative mean cardiac
      index was 2.7 +/- 7 l/min/m2, mean pulmonary artery pressure was 29.9 +/- 7 mm Hg
      and contractility score (generated by appropriate software for left ventricular
      kinesis analysis) mean value was 50.1 +/- 11.6 points. Urgent operation was
      required in 32 pts (16%). The majority of pts were completely revascularized.
      RESULTS: Operative mortality was 9% (18 pts). Low output syndrome was the most
      common postoperative complication (13.5%) followed by ventricular arrhythmia
      (8%), mean length of postoperative hospitalization for survivors was 13 +/- 10
      days. Of 23 possible operative risk factors evaluated, four were associated with
      significantly greater mortality: cardiac index < or = 2.1 l/min/m2, urgent
      operation, contractility score > or = 80 and associated surgical procedures.
      Survivors experienced significant improvement in CHF class (p < 0.001) and follow
      up EF (p < 0.001). Kaplan-Meier estimate of survival at 1 year, 5 years and 8
      years was 85%, 65% and 54%. CONCLUSION: Through more careful assessment of
      preoperative risk factors, patients selection and perioperative management,
      actually coronary artery bypass graft may be offered to pts with low ejection
      fraction with reduced morbidity and mortality.

PMID- 9005160
TI  - [Percutaneous radial approach for coronary angiography].
AB  - BACKGROUND: The Sones technique for coronary angiography has been abandoned by
      most of laboratories. Nevertheless, in some circumstances (anticoagulation,
      peripheral arteriopathy, outpatients procedures), the femoral entry site may be
      troublesome. We evaluated the feasibility and safety of percutaneous transradial
      approach to coronary angiography as an alternative way to the usual femoral
      approach. METHODS: Since July to october 1995 we performed 200 consecutive
      coronary angiographies via radial artery with percutaneous approach. Exclusion
      criteria were the absence of radial pulse, abnormal Allen test and the need to
      perform right catheterism. No patient was excluded because of age or other
      clinical reason. We used right radial artery in 192 cases, left radial artery in
      7 cases and both right and left artery in 7 cases. Thirteen patients (6.5%) had
      previous CABG. Thirteen patients were under treatment with heparin or dicoumarol.
      Twenty-one patients (10.5%) were affected by lower extremities arteriopathy. Five
      patients had previous coronary angiography by Sones technique. Fifty-eight
      patients (29%) underwent coronary angiography on outpatient basis. We used 6 F
      catheters in all cases but one. 5000 UI heparin bolus was injected in all cases.
      Sheaths were pull-out immediately after the procedure. We used Judkins L 3.5 and
      Judkins R 4 as first choice catheter. RESULTS: We succeeded in performing a
      complete coronary angiography in 189 patients (94.5%). In 11 patients the
      angiography had to be performed or completed by femoral approach: we failed in
      radial artery puncture in 5 patients; in 2 patients the guidewire could not be
      advanced beyond brachial bifurcation; in 1 very tall patient the catheter distal
      extremity did not reach coronary ostia; in 1 case were not able to do selective
      injection in left coronary ostium because of brachiocephalic trunk tortuosity; in
      2 patients resistant radial artery spasm occurred. It was necessary to change the
      first choice catheter in 17 patients (8.5%) for left coronary artery and in 4
      patients (2%) for right coronary artery. Clinical complications were ventricular
      fibrillation in 1 case and vasovagal reaction in 3 cases. Local complications
      were mild haematic effusion in 5 cases, small haematomas in 2 cases. In 12
      patients radial artery pulsations were not palpable at discharge; in 4 of them
      radial artery pulse spontaneously reappeared after a week. CONCLUSIONS:
      Percutaneous transradial approach for coronary angiography is safe and feasible
      and represents a good alternative entry method mainly in patients with peripheral
      arteriopathy, in patients treated with anticoagulants and in outpatients coronary
      angiography.

PMID- 9005161
TI  - [Recovery evaluation in a pediatric heart surgery unit using the AP-DRG
      classification system (All Patient Diagnosis Related Groups)].
AB  - The evaluation of Health Care activities, particularly of those concerning
      hospitals, is one of the most important aims for the National Health Service for
      a "fair" resource allocation. In the recent past a great bulk of research has
      been directed to methods for patient classifications in relation to resource
      needs. Diagnosis Related Groups (DRG) is one of the most important patient
      classification systems related to resource allocation which has been developed in
      the U.S. Medicare Program (HCFA-DRGs) during the eighties and more recently
      adopted all over Europe, Italy included. Wide experimentation has been developed
      during the recent past concerning DRGs confirming its validity, but also has
      disclosed its limits, mostly concerning applicability outside U.S.,
      identification of specific patient subgroups (like the pediatric patient
      population) and capability in distinguishing patients with apparently similar
      resource needs, but different clinical severity conditions. In order to overcome
      such limits, DRGs have been subjected to some important modification: All patient
      DRG (AP-DRG) is a system which should pay more attention to some patient
      subgroups, such as the pediatric one. Research is still looking for methods,
      easily extensible to the whole hospital informative system concerning the
      possibility of distinguishing patients with different level of severity
      condition. With the double aim of experiment the actual utility in the use of AP
      DRG, more than HCFA-DRG in a pediatric population and find further indexes for
      complexity and/or severity characterization of the hospital case-mix, the 1992 in
      patients hospital files of the pediatric cardiosurgery hospital CREAS-IFC-CNR was
      reviewed. Results confirm that some increase in the identification of the case
      mix do occur by using the AP-DRG system, even if a better clinical
      characterization could be possible (i.e. AP-DRG 108). Of particular interest is
      the fact that descriptive statistical analysis of position and variability
      parameters do confirm the importance of the length of stay as a brief index for
      hospital efficiency evaluation and its organizative model characterization.

PMID- 9005162
TI  - [Computerized follow-up cards for ambulatory patients with implanted pacemaker or
      defibrillator].
AB  - The follow up of pacemaker and defibrillator dependent patients has a significant
      role for both the evaluation of pacing effectiveness and check of hemodynamic
      advantages about patient's quality of life. The bulky paper archives are often
      inaccurate, hampering the consultation. At present the paper card is the only
      document which can be utilized to record some data concerning the implant and
      patient clinical story. Therefore, there is the necessity for a card that can
      include all patient's data, and the implant and programming
      pacemaker/defibrillator data during follow up. This new pacemaker card has
      portable file or data-base including shared data with safety mechanism, which can
      be utilized in several controls by different users (physicians, hospital ward,
      primary care units, insurance companies). The pacemaker card includes a chip that
      permits to store a considerable amount of data; it can be update in every further
      medical control, in observance of laws. The card Chip Operating System (C.O.S.)
      consists of a microchip with a memory completely managed by the operating system
      inside the chip itself. The card can be read by means of a GCR-200 modem linked
      with a PC IBM-compatible computer and the data can be updated during the follow
      up. The pacemaker-defibrillator card will appear immediately on screen, and it
      can be printed, updated and/or modified by a Microsoft Windows operating
      programme. With this pacemaker card we are able to ensure serviceable medical
      work, particularly in terms of cost/benefit ratio giving to patient more and more
      reasoning and safe service.

PMID- 9005163
TI  - [A paradigmatic case of partial agenesis of the pericardium].
AB  - Complete or partial absence of the pericardium is an uncommon congenital
      abnormality. Since its first description, several cases have been reported.
      Although the clinical and instrumental features of this defect are well
      described, at present it is often overlooked. We report a case of a 19-year old
      boy referred to our Echocardiography laboratory because of a suspected
      interatrial septal defect. For this reason it has been recommended to undergo
      cardiac catheterization. The patient, completely asymptomatic, had a negative
      physical examination. The echocardiogram excluded the presence of an interatrial
      septal defect, but some abnormalities, regarding overall right-sided heart, were
      found (paradoxical interventricular septal movement, apparent right-sided heart
      enlargement, with unusual bulging of the apex of the right ventricle, an
      excessive basculant heart movement). In the absence of any other heart disease,
      we thought that these abnormalities reflected a congenital absence of the
      pericardium. Indeed, the chest X-ray showed some features, considered
      patognomonic for congenital absence of the pericardium (levoposition of the
      heart, lung interposition between the diaphragm and the base of the heart and
      between the aorta and pulmonary artery). Nuclear magnetic resonance study showed
      the absence of the pericardium in the posterior and posterolateral wall,
      confirming our suspicion. Furthermore, the posterior wall of the heart leaned to
      herniate through the pericardial defect. Since the partial absence of the
      pericardium can lead to severe complications, surgery was recommended. The
      correct diagnosis of this disease is very important because of its prognostic
      implications; this case represents a further contribution to the understanding of
      this defect.

PMID- 9005164
TI  - [Corrected transposition of the great arteries in geriatric age. Report of a case
      diagnosed by magnetic resonance imaging].
AB  - Corrected transposition of the great arteries (cTGA) is a rare condition, and few
      patients with this abnormality survive the 50th year of age because of associated
      anomalies or the subsequent development of left atrioventricular valve
      regurgitation or heart block or both. We report the case of a 75 years old man
      with cTGA without associated anomalies which seems to be of particular interest
      because of the following reasons: 1) cTGA is a rare condition in advanced age; 2)
      the diagnosis has been made by MRI which allowed a complete segmental analysis;
      3) this case confirms that the morphologic right ventricle in systemic position
      can function appropriately over a long term. We conclude that MRI can be an
      alternative to Echocardiography in patients with complex congenital cardiac
      disease who exhibit a poor ultrasound window.

PMID- 9005165
TI  - [Lipoprotein(a) as an athero-thrombotic risk factor: epidemiologic evidence and
      possible pathogenetic mechanisms].
AB  - Lipoprotein (a) [Lp(a)] has been known for more than 20 years as a peculiar
      "variant" of low-density lipoproteins (LDL), the recent interest for which mostly
      derives from its epidemiological and maybe pathogenetic link with coronary artery
      disease and atherosclerosis. The protein moiety of Lp(a)-apo(a)-is a glycoprotein
      produced by the liver, with evident structural analogies with plasminogen. A
      large variety of apo(a) isoforms have been described, with large variability in
      molecular weight, encoded by alleles located on chromosome 6. Plasma
      concentrations of Lp(a) are largely genetically determined, but variations on
      these levels are induced by changes in hepatic synthesis due to changes in
      control factors (for example in proteinuric syndromes). Many-but not univocal
      epidemiological pieces of evidence indicate that high plasma concentrations of
      Lp(a) are associated with atherosclerosis and its cardiac, cerebral and
      peripheral manifestations, thereby potentially identifying a new cardiovascular
      risk factor, independent from plasma concentrations of LDL. This review will
      discuss such evidence and the mechanisms potentially linking Lp(a) and
      atherosclerosis. Proposed mechanisms include, among others, the susceptibility of
      Lp(a) to oxidation, the interference with mechanisms of fibrinolysis and the
      induction of endothelial activation.

PMID- 9005166
TI  - [Clinical research today. (Reflections of a pessimist)].

PMID- 9005167
TI  - [Quality and health: a new dimension for promoting an ethical culture of wider
      scope].

PMID- 9005169
TI  - [Clinical relevance and methodological limitations of the determination of atrial
      natriuretic peptide (ANP) in chronic heart failure].

PMID- 9005168
TI  - [Acute changes in the hemodynamic profile and circulating levels of atrial
      natriuretic peptide induced by dobutamine in severe heart failure].
AB  - METHODS: Sixteen patients (15 males, 1 female; mean age 63 years, range 45-78)
      with severe heart failure (NYHA class III = 5; class IV = 11) secondary to
      ischemic heart disease (8), dilated cardiomyopathy (5) and valvular heart disease
      (3), were evaluated for eligibility to intermittent Dobutamine (D) treatment. As
      a part of this evaluation, they were submitted to an acute dose-ranging test with
      D, up to 10 micrograms/Kg/min under hemodynamic and electrocardiographic
      monitoring. By inclusion criteria, all patients had:-cardiac index (CI) < 2.2
      L/min/m2;-pulmonary wedge pressure (WP) > 18 mmHg;-left ventricular ejection
      fraction (EF) < 30%. At each step of the procedure, hemodynamic measurements and
      blood sampling for atrial natriuretic peptide (ANP) concentration were performed.
      RESULTS: Peak effect, defined as the dose corresponding to the maximum increase
      in CI, was reached at a mean of 7.8 +/- 0.5 micrograms/Kg/min. CI increased from
      1.7 +/- 0.3 to 2.53 +/- 0.7 L/min/m2 (p < 0.001) and ANP decreased from 234 +/-
      112 to 173 +/- 118 pg/ml (p < 0.001). Correspondingly, heart rate, stroke volume
      index and stroke work index increased, while right atrial pressure (RAP), mean
      pulmonary artery pressure (PAP), WP, systemic and pulmonary vascular resistance
      all significantly decreased. Mean arterial pressure was not affected. Changes in
      ANP concentration correlate significantly with changes in WP and in PAP (r =
      0.65, p < 0.05 and r = 0.89, p < 0.001, respectively), but not with changes in
      RAP (r = 0.26, p = 0.34). Patients showing an increase > 40% in CI or a CI > or =
      2.5 L/min/m2 at peak effect (responders) had significantly lower baseline PAP
      with respect to non-responders. Besides PAP, baseline ANP levels, end-systolic
      pressure/volume ratio and ejection fraction were also independent predictors of
      response. The test did not induce complex arrhythmias and was well tolerated in
      all patients. CONCLUSIONS: Patients with severe heart failure retain the ability
      to respond to acute administration of D. with a significant improvement in their
      hemodynamic profile. Response to D. administration is predicted by lower baseline
      pulmonary pressure and ANP levels and a lesser degree of left ventricular
      dysfunction. Despite high baseline ANP concentration, a significant decrease is
      obtained which parallels the decrease in pulmonary artery and pulmonary wedge
      pressure, but is not related to changes in right atrial pressure. These findings
      suggest that changes in left ventricular performance induced by D. are the major
      determinants of the decrease in ANP concentration in this clinical setting.

PMID- 9005171
TI  - [Asymptomatic left ventricular myxoma in pregnancy: echocardiographic diagnosis
      and surgical treatment].
AB  - Myxoma arising from the endocardial wall of the ventricles is rare. We describe
      here the case of a young woman in whom an asymptomatic left ventricular myxoma
      was incidentally discovered at the 35th week of pregnancy by transthoracic
      echocardiography. The echocardiogram revealed a huge intraventricular mass
      attached to the apex and prolapsing to the aortic valve during systole. On the
      basis of this ominous feature, the woman was promptly submitted to caesarean
      section and, after 10 days, to surgical removal of the mass.

PMID- 9005170
TI  - [Effects of naloxone on plasma levels of atrial natriuretic factor and
      noradrenaline during water load in moderate heart failure].
AB  - BACKGROUND: The aim of our study was to evaluate the effects of endogenous
      opioids on the secretion of atrial natriuretic factor (ANF) in moderate chronic
      heart failure (HF). METHODS: We evaluated the effects of i.v. volume load (NaCl
      0.9% at 0.25 ml/Kg/min for 60 minutes) on heart rate (HR), on mean arterial
      pressure (MAP) and on the plasma levels of beta-endorphin (beta-end), met
      enkephalin (Met-enk), dynorphin (Dyn), atrial natriuretic factor (ANF) and
      noradrenaline (NA) in 10 patients (age 58 +/- 9) with HF in NYHA class II (group
      I) and in 8 healthy control subjects (age 54 +/- 10) group II). The volume load
      was repeated after at least three days during infusion of naloxone (2
      micrograms/Kg/min), evaluating the above mentioned hemodynamic and hormonal
      parameters. RESULTS: The acute volume expansion caused an increase in ANF
      concentration (from 51.7 +/- 19.7 to 67.4 +/- 36.9 pg/ml; p < 0.05) and in beta
      end (from 11.9 +/- 5.3 to 16.6 +/- 7.5 fmol/ml; p < 0.05), In group I. In group
      II an isolated increase in ANF was observed (from 14.1 +/- 7.8 to 21.9 +/- 7.9
      pg/ml; p < 0.02). No significant changes were detected for HR, MAP, Dyn, Met-enk
      and NA. In group I the percent increase of ANF is less than in group II (30 vs
      55%; p < 0.05). The volume load infused during naloxone infusion caused a
      significant increase in HR (from 73 +/- 6 to 78 +/- 9 bpm; p < 0.05) and in NA
      (from 311 +/- 123 to 415 +/- 142 pg/ml; p < 0.05) In group I. In group II, an
      increase in ANF was detected (from 13.8 +/- 6.0 to 23.6 +/- 5.0 pg/ml; p < 0.01).
      CONCLUSIONS: Our data suggest that in moderate HF beta-end stimulates the
      secretion of ANF and inhibits the activity of the sympatho-adrenergic system
      during acute volume expansion.

PMID- 9005172
TI  - [Hypertension secondary to multiple malignant paragangliomas].
AB  - We describe a case of severe hypertension, due to multiple malignant
      norepinephrine secreting paragangliomas. Neuroendocrine system tumours are
      responsible for 0.1-0.5% cases of hypertension. Their extra-adrenal localisation
      is about 10%. Only 20% of paragangliomas are catecholamine secreting, and causing
      a syndrome similar to that of pheochromocytoma. In our patient the diagnosis of
      retroperitoneal multiple paragangliomas was made two years after the beginning of
      the typical symptoms. At surgery 6 paragangliomas were removed; some vascular and
      muscular structures (inferior vena cava, ileopsoas) were infiltrated. A
      radiotherapy treatment was conducted for a total dose of 55.8 Gy. Immediately
      after the operation blood pressure decreased, but the administration of alpha and
      beta blockers was required to reach normotension. This treatment was confirmed at
      six months follow-up, in consideration of the persistently high norepinephrine
      plasma levels.

PMID- 9005174
TI  - [The market in medicine: general and ethical considerations].

PMID- 9005173
TI  - [Hormone replacement therapy and cardiovascular risk].
AB  - Coronary artery disease is the main cause of death and morbidity in both genders,
      in Italy as well as in other Western populations. Nonetheless, striking sex
      differences in the incidence of coronary artery disease exist, with a relative
      protection in fertile women. This protection is mostly lost in the post
      menopause. Several lines of evidence indicate that this relative protection is
      due to the effects of ovarian hormones. In the last 10 years the great
      opportunity to prevent or reduce the occurrence of coronary artery disease in
      post-menopausal women by hormone replacement therapy has been appreciated. This
      review examines the effects of hormone replacement therapy on cardiovascular risk
      and its possible mechanisms. Epidemiological and observational evidence supports
      the notion of protective effects of estrogens. This may occur through favorable
      changes on lipid risk factors (a decrease in plasma levels of total and LDL
      cholesterol and an increase in HDL-cholesterol), on the vessel wall (endothelial
      and smooth muscle cells) and on the development of atherosclerosis. Active
      investigational areas are the search for molecular mechanisms through which
      estrogens-with or without progestogens-modulate the vascular response to
      vasoactive agents, endothelial and smooth muscle cell biology, hemostasis and
      glucose metabolism. There is, however, a lack of adequate prospective studies to
      evaluate the effects of estrogens-alone or in combination with progestogens-on
      hard end-points such as total and cardiovascular mortality and morbidity. In
      addition to this, there is still substantial disagreement on the possible risks,
      mostly breast cancer, of hormone replacement therapy. At the moment, the
      evaluation on the opportunity to start hormone replacement therapy in post
      menopausal women has to be strictly personalized, by adequately balancing
      potential risks and probable benefits.

PMID- 9005175
TI  - [Cardiological protocols on determining eligibility for competitive sports 1995.
      Organizational Cardiological Committee on Eligibility for Sports (COCIS)].

PMID- 9005176
TI  - [Experimental studies on the effect of the dust of phosphogypsum and its
      derivatives].
AB  - The acute toxicity of phosphogypsum and its derivatives was studied. The agents
      were found to be low and moderate toxic.

PMID- 9005178
TI  - [A new All-Union State Standard R 50723-94 on laser safety and use of laser
      items].

PMID- 9005177
TI  - [Features of the functional state of railway passenger coach porters].

PMID- 9005179
TI  - [Hygienic evaluation and prognosis of factual nutrition status of individual
      groups of the population of Russia].
AB  - The real nutrition of population groups in four large regions of Russia over the
      past ten years was studied. Scientific forecast of food and energy consumption
      till 2002 was made. Priorities of diet rationalization of different population
      groups were forwarded.

PMID- 9005180
TI  - [Hygienic problems in the use of computers by school children with refractive
      disorders].
AB  - The influence of 0.5-hour computer loading on accommodation, critical frequency
      of a flicker, vision capacity for work, the function of the central nervous
      system was studied. Significant functional changes were revealed in
      schoolchildren with myopia. Protective screens were found to improve their
      functional indices. Therefore, children with myopia should be identified as a
      risk group to regulate their work regimen.

PMID- 9005181
TI  - [Hygienic significance of several blood and urine indicators in chronic mercury
      poisoning in school children].

PMID- 9005182
TI  - [Hygienic aspects of health of children living in areas with developed gas
      chemical industries (review)].

PMID- 9005183
TI  - [Interactions of biosystems with low-frequency electric fields (theoretical
      aspect)].

PMID- 9005184
TI  - [Optimization of conditions of ozone water disinfection by the method of the
      mathematical planning of an experiment].
AB  - A mathematical model for searching the optimum conditions of ozone water
      disinfection was developed. Experiments and field investigations showed the
      adequacy of the developed model for this research area. It makes it possible to
      use the model to calculate the optimal ozone dose and the results of ozone water
      disinfection.

PMID- 9005185
TI  - [Environmental radiation pollution and internal irradiation of children].

PMID- 9005186
TI  - [Problems of environmental optimization in the European North].

PMID- 9005187
TI  - [Dynamics of immune response to single exposure to low-frequency acoustic
      oscillations].

PMID- 9005188
TI  - [Noise as a factor of work environment in manufacturing of synthetic fiber].

PMID- 9005190
TI  - [Four periods of the history of Russian hygiene].

PMID- 9005189
TI  - [Economic assessment of damage caused to population's health by radiation
      pollution of the environment].

PMID- 9005191
TI  - [Anniversary dates of history of hygiene and sanitation in 1996].

PMID- 9005192
TI  - [Improvement of a portable device for isolation of bacteria from the air under
      study].

PMID- 9005193
TI  - [Gas chromatographic determination of dicyclohexyl ethers of succinic, glutaric
      and adipic acids in the workplace air].

PMID- 9005194
TI  - [Test method for monitoring chloramine concentration in disinfectant solutions].

PMID- 9005195
TI  - [Rapid method of the determination of carbon dioxide in the air of premises].

PMID- 9005196
TI  - [Protection of water supply sources from synthetic surface-active agents
      (review)].

PMID- 9005197
TI  - [Hygienic evaluation of combined biotechnology for treating sewage from
      artificial accumulations].
AB  - Combined biotechnology for treating sewage and industrial wastes with Pseudomonas
      fluorescens bacteria and Scirpus lacustris L. reed mass was developed. The
      treated waters can be discharged into the surface reservoirs.

PMID- 9005199
TI  - [Without the family physician drug treatment is not feasible. Interview by Dr.
      rer. nat. Anita Schweiger].

PMID- 9005200
TI  - [Alcohol abuse: ever earlier, ever more frequent. A study shows correlation with
      early childhood anxiety disorders].

PMID- 9005201
TI  - [Alcoholism as chronic disease: a challenge for the physician].
AB  - Alcoholism is associated with a high relapse rate; within four years of a
      successful intensive hospital withdrawal program a good 50 percent of the
      patients have relapsed again. In view of this result of research into alcoholism
      an "aims hierarchy" has been established which meets the requirements of relapsed
      alcoholics while expressly rejecting the limitation of therapeutic measures to
      the purely somatic. Psychotherapeutic considerations that take account of the
      specific situation of the chronic, often multimorbid patient are applied already
      in the early phase of treatment. For example, relapse must not be interpreted as
      a failure of previous treatments or even be used as an excuse to abandon therapy.

PMID- 9005198
TI  - [Tracking down natural resistance to HIV. Defective cellular receptor prevents
      entrance of virus into the cell].

PMID- 9005202
TI  - [Is drug dependence an occupational risk for physicians?].
AB  - Physicians are probably a high-risk group for the development of dependency. In
      addition to the particular demands associated with the profession of medicine,
      another cause is to be sought in the specific aspects of a doctor's personality.
      Occupational stress and an inability to develop adequate compensatory mechanisms
      can lead to burnout and addiction. Over and beyond treatment, rational
      prophylaxis is urgently required, and this should not fail to include a critical
      consideration of the self-image of the medical profession.

PMID- 9005203
TI  - [Alcohol at the wheel--medical psychological expert assessment. Laboratory data
      and abstinence--prognosis--responsibilities of the family physician].

PMID- 9005205
TI  - [Therapy of the patient with chronic renal failure. A study from general practice
      of an ambulatory dialysis center].

PMID- 9005204
TI  - [Chronic venous insufficiency--from pathophysiology to therapy. 3: Physical
      therapy of venous diseases].
AB  - In patients with chronic venous insufficiency (CVI), stage-oriented physiotherapy
      can be employed in addition to surgery, drug treatment and sclerotherapy, with
      both prophylactic and curative intent. Apart from improving the hemodynamic
      situation, physiotherapy aims in particular to preserve or reactivate the active
      and passive pump mechanisms of the lower limbs, for example, the calf muscle pump
      and the ankle pump. Consequently the wide spectrum of physiotherapeutic measures
      includes such measures as compression therapy, anticongestion positioning,
      massage and exercise, all of which can be supplemented or replaced, as didacted
      by the condition prevailing, by hydrotherapy, electrotherapy, balneotherapy or
      climatic therapy.

PMID- 9005206
TI  - [Insomnia--diagnostic and therapeutic procedure. 1: Definitions and
      classifications--diagnostic procedure in general practice].

PMID- 9005207
TI  - [Cell membrane receptors and intracellular signalling. Characterization in
      cultivated, contractile and endothelial cells].
AB  - Numerous hormones and mediators develop their effect via one or several specific
      receptors/subtypes. In glomerular endothelial cells (GEC), for example, the
      action of adenosine triphosphate is mediated by a novel nucleotide receptor.
      Since the latter is not found in large vessels, it is expected to play an
      important role in the regulation of the microcirculation. Substances with a very
      similar structure, such as vasopressin and oxytocin, can bind to the same
      receptor in vascular smooth muscle cells (VMC), although only the true agonist
      produces a maximum response. Following the binding of vasopressin to its specific
      V1-VP receptor, the ligand/receptor complex is internalized and processed within
      the cell. The freed receptor is then recycled to the cell membrane. This
      mechanism is responsible for the transient nature of vasopressin action. In VMC
      and the functionally similar contractile glomerular mesangial cells, vasopressin
      triggers intracellular signals, resulting in contraction. These signals may be
      enhanced or attenuated by numerous hormonal factors or mediators.

PMID- 9005208
TI  - [L-tryptophan is available again. Interview by Dr. rer. nat. Till Uwe Keil].

PMID- 9005209
TI  - [Cerebral stimulation--methods for invasive and non-invasive brain function
      tests].

PMID- 9005210
TI  - [Recent findings on hereditary peripheral nerve dysfunctions].

PMID- 9005211
TI  - Mitochondrial DNA Haplogroups in Four Tribes from Tierra del Fuego-Patagonia:
      Inferences about the Peopling of the Americas.

PMID- 9005212
TI  - The significance of immune suppression in normal self tolerance.

PMID- 9005213
TI  - A model for developmentally acquired thymus-dependent tolerance to central and
      peripheral antigens.
AB  - Current models of tolerance to peripheral, tissue-specific antigens contain some
      major caveats. First, they consider peripheral tolerance independently from
      intrathymic T cell selection, a dichotomy that is challenged by observations on
      TE-induced tolerance. Second, they do not account for the fact that vertebrates
      are more readily tolerised in development than in adult life. Third, they do not
      explain the fact that embryonic/neonatal tolerance to foreign tissues can only be
      induced by HC or TE. A model of thymic selection and peripheral tolerance is
      developed here that resolves those problems, by assuming two classes of T cell
      effector functions, one being regulatory and the other aggressive. Three
      postulates are required: (1) both epithelial and hemopoietic cellular
      compartments of the thymic stroma can support both positive and negative
      selection of T cells, but with vastly different avidity requirements and
      efficiency; (2) positively selected T cells with the highest avidity that escape
      deletion are activated intrathymically and irreversibly committed for regulatory
      effector functions; (3) the functional phenotype of all other thymic emigrants is
      determined in the periphery upon encounter with antigen. Functional commitment in
      the periphery depends on the maturity stage (RTE or PMR) of the immunocompetent
      cell, on the nature of the antigen-presenting cells, and on the effector classes
      of other T lymphocytes interacting on the same presenting cell. This model
      explains a number of observations on experimental autoimmune disease and
      transplantation tolerance, and it contains several readily testable predictions.

PMID- 9005214
TI  - Immune deviation--the third dimension of nondeletional T cell tolerance.

PMID- 9005215
TI  - The physiological role of regulatory T cells in the prevention of autoimmunity:
      the function of the thymus in the generation of the regulatory T cell subset.

PMID- 9005217
TI  - The shaping of the brain-specific T lymphocyte repertoire in the thymus.
AB  - We have shown in several distinct experimental systems that the immune system of
      intact Lewis rats contains T cells which, upon activation, are able to mediate
      autoimmune brain inflammation. These T cells seem to differentiate within the
      thymus although the autoantigens are produced (and presumably expressed in a
      recognizable fashion) within the thymic medulla. Furthermore, an intact fully MHC
      compatible thymic microenvironment seems to be required for the development of
      all features of the autoimmune TCR repertoire. Biased utilization of V beta 8.2
      gene for the TCR, a hallmark of the Lewis rat T cell response to MBP, is only
      seen in T cells having matured in thymuses entirely composed of stroma elements
      of rat origin. It seems that the thymus contains a large spectrum of protein
      structures, which hitherto had been considered autoantigens specific for
      "peripheral" tissues, and, most surprisingly, components of the CNS, the
      classical "sequestered" organ. Deletion of autoreactive T cell clones by many
      local intrathymic autoantigens is leaky, at best. The reduced expression of CD4
      on thymus-derived autoreactive T cells may be construed to reflect abortive
      efforts of negative selection. Alternatively, however, it may be worthwhile to
      consider a positive role for intrathymic autoantigens and their complementary T
      cells clones. It is possible that the requirement of an intact thymus milieu for
      the typical, V beta 8.2 dominated MBP specific T cell repertoire in the Lewis rat
      could reflect self peptide presentation by thymus epithelium cells in positive
      selection stages. In that case, the unusual diversity of thymic autoantigens
      could indeed have a role in shaping the immune system's TCR diversity, possible
      in the sense of an "immunological homunculus" as postulated by Cohen (Cohen
      1992). Finally, there is a need to explain the mechanisms that in the healthy
      organism prevent the numerous, potentially autoaggressive T cell clones from
      attacking the body's own tissues. This is especially important, as T cells
      reactive against potentially pathogenic autoantigens, e.g. MBP (Ota et al. 1990,
      Pette et al. 1990b) and acetylcholine receptor (Salvetti et al. 1991, Sommer et
      al. 1991), are seen at especially high frequency in the human immune repertoire.
      Clearly, in all experimental paradigms investigated, activation of self-reactive
      T cells was the critical prerequisite for induction of autoimmune disease. Thus,
      in principle, prevention of such activation would be one way to maintain self
      tolerance. The mechanisms that achieve this goal in most individuals remain to be
      elucidated.

PMID- 9005216
TI  - Double negative (CD4-CD8- alpha beta+) T cells which promote tolerance induction
      and regulate autoimmunity.

PMID- 9005218
TI  - Evidence for a thymus-dependent form of tolerance that is not based on
      elimination or anergy of reactive T cells.
AB  - The avian embryo has provided an appropriate model to study the ontogeny of the
      primary lymphoid organs, thymus and bursa of Fabricius. By using the quail-chick
      marker system the embryonic origin of the highly intricate cell components which
      form these organs could be traced back to the initial endodermal, mesodermal and
      ectodermal germ layers. The timing and dynamics of the incoming and outcoming
      flows of hemopoietic cells which characterize their lymphopoietic activity could
      be revealed in both quail and chick embryos. This knowledge served as a basis for
      an investigation on the role of the epithelial component of the thymus (derived
      from the pharyngeal endoderm) on tolerance to tissue graft and, by extension,
      tolerance to self. When this work was undertaken, the prevailing view was that
      exposure of the developing immune system to foreign antigens in the embryo allows
      them to be assimilated to self components in the mature animal. In fact, this was
      found to be true for allogeneic grafts between MHC-distinct chickens, of certain
      tissues, such as for instance wing tissues. However, in heterospecific
      transplantations, i.e. when a limb bud was grafted from quail to chick embryos,
      the chick host acutely rejected the foreign limb soon after birth. In contrast,
      grafts of the quail thymic epithelial (TE) rudiment resulted in the development
      of a chimeric thymus in which the foreign epithelial component was not only
      tolerated but able to induce full tolerance of the grafted wing from the same
      donor. By monitoring the amount of quail TE implanted we showed in addition that
      only part of the peripheral T-cell population had to differentiate in the context
      of the quail epithelial cells to induce tolerance to quail tissues. This pointed
      to the generation in the thymus of regulatory T cells, coexisting with specific
      anti-quail reactive T cells, but able to inhibit them from reacting against the
      quail wing antigenic determinants. A mammalian model was then devised to further
      study this mechanism of tolerance that we have qualified as "dominant" by
      opposition to the current model based on either clonal elimination or anergy
      which can be considered as recessive or passive. Nude mice of MHC type A were
      grafted with TE of E10 type B embryos. They became reconstituted for T-cell
      function but tolerant for B skin allografts. Spleen cells from such tolerant
      animals injected to naive A nude mice reconstituted T cell function in the
      recipient and transferred the tolerance to B skin grafts. Reducing the number of
      donor cells resulted in the segregation of the two phenomena. For low numbers the
      recipients were restored but not tolerant, thus showing the coexistence in the
      tolerant donor of anti-B reactive T cells together with regulatory cells able to
      abolish their reactivity against B determinants. Other experiments demonstrated
      that TE-induced tolerance does not rely on clonal deletion or anergy. This was
      shown on systems where elimination of cells directed toward superantigens was
      screened. It turned out that tolerance to skin grafts and superantigen T-cell
      deletion are unrelated phenomena. These observations strongly suggest that
      tolerance to self results at least in part from the interplay between cells
      potentially harmful for self component and others which exert a strong control on
      their reactivity. The latter cell type depends upon interactions of thymocytes
      with the endodermal component of the thymus.

PMID- 9005219
TI  - Mechanisms of peripheral tolerance and suppression induced by monoclonal
      antibodies to CD4 and CD8.
AB  - Over the last five years it has become increasingly clear that the peripheral
      immune system can maintain tolerance to both self and non-self antigens through a
      variety of mechanisms. Although clonal deletion may play an important part in
      limiting rapidly expanding responses, there are many examples where antigen
      reactive T cells remain. It has been proposed that tolerance is maintained in
      this situation either by the induction of anergy or by ongoing suppression. The
      phenomenon known as immune deviation, where non-inflammatory Th2 responses could
      suppress Th1 and positively reinforce themselves provided an attractive
      explanation for infectious tolerance, where tolerant T cells could guide further
      naive T cells also to tolerance. However, experiments to test this hypothesis in
      the models of CD4 and CD8 antibody-induced tolerance have given conflicting data,
      with no clear evidence of Th2 responses in tolerant mice. In this paper we review
      recent data that IL-4 plays a role in suppression, but that the source of IL-4
      may not be the tolerant/suppressor T cell. We also discuss how infectious
      tolerance can operate on third party antigens if they are linked on the same
      antigen presenting cell and how CD4+ T cells can suppress CD8+ T-cell responses.
      Finally, we suggest a model of infectious anergy that is compatible with the
      available data.

PMID- 9005220
TI  - (Altered) self peptides and the regulation of self reactivity in the peripheral T
      cell pool.
AB  - Tolerance for self has appeared incomplete for many self antigens. We have
      obtained experimental evidence that both for self heat shock proteins and T cell
      receptor V-gene products, reactive T cells are part of the normal immune
      repertoire. Furthermore, it has become apparent that stimulation of T cell
      responsiveness to these antigens, by using peptide immunisation or by transfer of
      activated T cells, raises resistance to experimentally induced autoimmune
      arthritis. In addition, available evidence has suggested that these reactivities
      may be functional during natural processes of disease remission. The observations
      with regard to heat-shock proteins have indicated that mechanism leading to
      disease resistance are most efficiently triggered by exposing the immune system
      to non-self antigens such as bacterial hsp's, which are similar to, but not
      identical to, self. Experimental evidence has been obtained, that conserved
      bacterial hsp peptides, may trigger self hsp reactive T cells, with disease
      suppressive regulatory potential. It is possible that such self hsp reactive T
      cells, being expanded by recognising bacterial peptides as full agonists, do, in
      fact, perceive the self epitopes as partial agonists, and therefore have the
      possibility of displaying downregulatory activity at the site of inflammation.
      Experiments with peptide analogs of self epitopes, being variants of disease
      critical T cell epitopes, have indeed suggested that also their activity in
      modulating disease may comply with the principles of dominant immunological
      tolerance.

PMID- 9005221
TI  - Pancreatic islet allograft immunity and tolerance: the two-signal hypothesis
      revisited.
AB  - The principle assumption of this discussion is that costimulation (CoS) forms the
      primary stimulus that compels T cells to mount a response to their specific
      antigen. However, this response can be either positive or negative, depending on
      the developmental stage of the T cell and the microenvironment in which the
      antigen and CoS are received. Thus, both immunity and tolerance may represent
      different outcomes of a two-signal process. We would emphasize that CoS is a
      functional term and not a strict molecular definition. While many molecular
      interactions have been described as providing CoS activity, notably those
      involving the B-7 family of cell surface molecules, it is not yet clear what
      combination(s) of non-antigen-specific signals may fulfil this function. This
      point is important because many studies have achieved tolerance through
      strategies designed to inhibit specific CoS molecules. However, it may be that
      differential signaling through distinct CoS molecules, rather than a global
      inhibition of CoS per se, plays a role in the generation of active tolerance in
      such studies (Bluestone 1995). A corollary of this notion is that antigen (signal
      1) delivery to T cells is a null event and so is not an inherently paralysing
      signal. Of course, if signal 1 is not itself a tolerogenic signal, then other
      mechanisms are necessary to explain many empirical observations of tolerance to
      allogeneic or self antigens. This is best illustrated by those forms of
      functional tolerance to either alloantigens or self antigens that do not appear
      to be the result of clonal deletion/inactivation. It would be relatively simple
      to invoke a model of tolerance whereby the relevant tissue-destructive cell is
      eliminated or inactivated; such a model would preclude the necessity to suggest
      active regulatory mechanisms of tolerance. However, in several model systems,
      including our own observations concerning tolerance induction to APC-depleted
      islet allografts, tissue-destructive T cells can persist in recipients tolerant
      to allogeneic or self antigens. Furthermore, there are key examples in which
      tolerance demonstrates a dominant phenotype; that is, tolerant cells can regulate
      the activity of naive, non-tolerant cells. This latter observation points to the
      function of an active, regulatory form of tolerance. As such, we would emphasize
      that tolerance should not be defined as unresponsiveness since the tolerant state
      is the consequence of very active immune reactions.

PMID- 9005222
TI  - Organ-specific autoimmunity induced by lymphopenia.

PMID- 9005223
TI  - Hibernoma of scalp: case report and review of literature.
AB  - Hibernomas are uncommon, benign neoplasms of adipose composed of brown fat. A
      review of the world literature revealed about 115 cases. These tumors are
      asymptomatic and slow-growing, commonly seen in the the interscapular region. We
      herein present the third documented case of a scalp hibernoma.

PMID- 9005225
TI  - Long-term follow-up of Hirschsprung's disease: review of early and late
      complications.
AB  - OBJECTIVE: Long term follow-up of Hirschsprung's disease to determine the early
      and late complications. DESIGN: Retrospective. SETTING: Tertiary care referral
      hospital. SUBJECTS: Fifty children who underwent either Swenson's procedure [SP]
      (n = 16) or Martin's modification of Duhamel's procedure [MDP] (n = 34), for
      treatment of Hirschsprung's disease during the period 1981 through 1990. RESULTS:
      Early complications observed were anastomotic leak (n = 4), stenosis (n = 8),
      wound infection (n = 8), and intestinal obstruction (n = 6). Follow-up period
      ranged from 2-10 years. Long term complications included constipation (n = 1),
      enterocolitis (n = 2), mild soiling (n = 4), and intestinal obstruction (n = 2).
      CONCLUSIONS: Early complications were seen with equal frequency in patients with
      either SP or MDP but late complications were seen less often with the SP. Both SP
      and MDP were equally effective in the definitive treatment of Hirschprung's
      disease.

PMID- 9005224
TI  - Prevalence of hypertension in schoolgoing children.
AB  - OBJECTIVE: To establish norms of blood pressure in children of different age
      groups, prevalence of hypertension and probable precipitating or aggravating
      factors. DESIGN: Cross sectional study. SETTING: Five thousand school children of
      Amritsar city. METHODS: Three readings of blood pressure were recorded. Norms for
      each year age group from 5-17 years of age were established. Persistently
      hypertensive children were investigated. Influencing factors like family history
      of hypertension and obesity were taken into account. RESULTS: The blood pressure
      increased with increase in age with a spurt in systolic blood pressure at the age
      of 12 years in both the sexes. There was no significant differences in the blood
      pressure of two sexes at various age groups except for systolic blood pressure at
      5,6 and 16 years and for diastolic blood pressure at 9 and 13 years. Only 0.46%
      children were hypertensive. Children with obesity (n = 342) and family history of
      hypertension (n = 271) had hypertension in 3.5% (n = 12) and 5.9% (n = 16) cases,
      respectively as compared to other children in which the prevalence was only 0.23%
      and 0.14%, respectively. CONCLUSIONS: The norms for determining hypertension in
      this population were established and it's prevalence was 0.46%. Significant risk
      factors were obesity and family history of hypertension.

PMID- 9005226
TI  - Future of patient records. Care for records for care: an appraisal of the
      practicalities of electronic patient record. Proceedings of the 8th European
      Health Records Conference. Maastricht, The Netherlands, May 21-24, 1996.

PMID- 9005227
TI  - Ultrasonic imaging of microscopic structures in living organs.
AB  - It is possible to estimate acoustic parameters that describe the microscopic
      anatomy of live tissues. The same rf echo signals used to form diagnostic
      ultrasound images undergo additional signal processing to compute D, the average
      scatterer size; SNR, a measure of the number density of scatterers; and IBC, a
      measure of tissue echogenicity. With these three parameters it is possible to
      identify the sources of ultrasonic scattering in kidneys, observe functional
      changes in live organs, and produce images of each parameter. Although this
      chapter has emphasized the more basic research elements of possible applications,
      similar methods have been used to study changes in tissue morphometry during the
      progress of disease and during the course of therapy in several organ systems.
      Advances in diagnostic ultrasound are providing safe and low-cost method for
      studying soft tissues in vivo.

PMID- 9005228
TI  - [Panendoscopy. Reliable routine method for staging squamous epithelial carcinomas
      of the upper aerodigestive tract?].

PMID- 9005229
TI  - [The time span between symptom onset and starting treatment in head and neck
      tumors].
AB  - The interval between the onset of symptoms in patients with head and neck cancers
      and the introduction of treatment was evaluated. During a 1-year period, patients
      were interviewed to determine the duration of any delays from the onset of
      complaints until the first visit to a doctor. Also asked was how long it took to
      be referred to an ENT specialist and actual referral to our department. We then
      determined the interval from diagnosis to the introduction of therapy. It was
      found that the delay of patients who went directly to an otorhino-laryngologist
      was shorter (median, 8 weeks) than that of patients who first went to their
      family doctors (median, 13 weeks) (P < 0.02). The latter then took an additional
      4 weeks before sending patients to an otorhinolaryngologist. Referral from the
      ENT specialist to our department took another 2 weeks, as well as our staging and
      pre-therapeutic management. Our findings show that the patient himself is the
      critical factor in delaying diagnosis and therapy. Tumor patients with greater
      professional qualification went to their doctors earlier (P < 0.0001) or more
      often went directly to an ENT specialist (P < 0.002). Consultations of physicians
      without experience in otorhinolaryngology caused yet further delays.

PMID- 9005230
TI  - [Laser Doppler flow signal frequency analysis in physiological and drug modified
      nasal flow motion].
AB  - The term "flow motion" stands for the phenomenon of spontaneous and autonomous
      rhythmic variations of the contractile state of the smooth muscles of small
      dermal vessels. There also have been a few observations of variations in the
      microcirculation of the mucosa, but they have not been evaluated in detail to
      date. The aims of this study were to develop a method for investigation flow
      motion, especially in the nasal mucosa; to compare nasal flow motion to that of
      other skin and mucosal areas; to evaluate the influence of normal saline
      solution, as well as a sympathomimetic agent and histamine on flow motion. The
      microcirculation of the nasal mucosa of 40 healthy volunteers was measured under
      standardized conditions. In a first series of investigations, the
      microcirculations of the forehead, lobule of the ear, nose and oral mucosa were
      compared. In the second series, the microcirculation of the nasal mucosa was
      measured with laser-Doppler flowmetry before and after provocation with 0.9%
      saline solution, 0.25 mg oxymetazoline hydrochloride as sympathicomimetic
      preparation and 0.085 mg histamine in 0.5 ml of 0.9% saline solution. Evaluation
      of the data included signal analysis of the microcirculatory variations using
      fast-Fourier transformation and its changes before and after the pharmacological
      stimulations. Distribution of the power spectra showed that the nasal mucosa was
      significantly different from that of the skin of the forehead and the ear.
      Oxymetazoline hydrochloride led to a clear increase and histamine to a
      significant reduction in the frequencies of the flow motion. The results of this
      study demonstrated that nasal flow motion could be detected and evaluated with
      laser-Doppler flowmetry and a special analysis of the data recorded. Specific
      patterns of the flow motion frequencies could be detected in the nasal mucosa
      that were distinctive from those of the skin. The pattern of the flow motion
      frequencies reacted very sensitively to the pharmacological provocations used.

PMID- 9005231
TI  - [Long-term results of endonasal frontal sinus surgery].
AB  - Most conditions of the frontal sinus requiring surgery can now be managed
      successfully by endonasal procedures. To date there has been no clear position
      regarding indications and results of different types of endonasal frontal sinus
      drainage. In a retrospective study we evaluated long-term results of Draf's type
      II and III endonasal frontal sinus drainages using endoscopy and computed
      tomography. Twelve to 98 months following type II drainage, 58% of 83 frontal
      sinuses were ventilated and normal. A ventilated frontal sinus but with
      hyperplastic mucosa was seen in 12%. Scarred occlusion with total opacification
      on CT occurred in 14%. Furthermore, total opacification in 16% was due to
      recurrent polyposis. Patients were free of symptoms or had only minor problems in
      79%. Twelve to 89 months following type III drainage, 59% of 81 frontal sinuses
      were ventilated and normal. A ventilated frontal sinus with hyperplastic mucosa
      was seen in 17%. Scarred occlusion with total opacification on CT was present in
      7%. Furthermore, total opacification in 16% was due to recurrent polyposis. In
      all, 95% of the patients were free of symptoms or had only minor problems.
      Combining our results with those of other authors and utilizing the physiology of
      wound healing after sinus surgery, we developed a protocol of differential
      indications for endonasal frontal sinus drainage.

PMID- 9005232
TI  - [Preoperative angiographic embolization of carotid glomus tumors. A method for
      improving operability].
AB  - During surgical resections carotid body tumors may bleed profusely due to their
      vascularity. Preoperative angiographic embolization of tumor-supplying arteries
      has reduced intraoperative blood loss significantly. The present study reviews
      our clinical experiences with 13 paragangliomas of the carotid bifurcation in 12
      patients during the past 5 years. In 6 patients (46.1%) computed tomography and
      magnetic resonance imaging demonstrated extensive spread of the tumor up to the
      base of the skull. Tumors of this size were initially assessed as being
      inoperable but curative surgical resections were performed after embolization of
      tumor-supplying arteries by intravascular injections of Gelfoam and implantations
      of microcoils. Vascular reconstruction of the internal carotid artery by a
      saphenous vein graft was required in 4 patients (30.7%). In 3 malignant
      paragangliomas (23.0%) adjuvant radiotherapy of 50-60 Gy was administered to the
      tumor site after surgery. During an average follow-up of 29 months, one malignant
      paraganglioma was found to have recurred locally 13 months after initial therapy.

PMID- 9005233
TI  - [Acoustic voice analysis. On documentation of voice rehabilitation after laser
      surgery laryngeal carcinoma resection].
AB  - Following curative minimal-invasive laser resection of T1-T3 laryngeal
      carcinomas, patients were subjected to an intensive voice rehabilitation. Therapy
      was effected twice a day for approximately 2 months, utilizing the concept of
      functional voice therapy. Before and after rehabilitation, acoustic analyses were
      made by using two different computer-supported measuring systems: (1) the
      "multidimensional voice program" (Kay Elementrics Corp.) and (2) a novel software
      program developed in Gottingen that includes a new voice quality parameter based
      on correlations between frequency bands. Acoustic analyses showed superiority of
      the glottal versus supraglottal compensatory phonation. Findings showed that not
      all acoustic parameters equally documented voice improvement after
      rehabilitation. The standard deviation of fundamental frequency was the only
      parameter showing a significant post-therapeutic improvement. A further suitable
      acoustic method proved to be the voice quality parameter that has been newly
      introduced by us. In contrast to analogous parameters of other methods, this
      approach is independent of the exact periodicity of the glottal excitation
      function, thus permitting reliable results to be obtained even with aphonic or
      heavily dysphonic voices.

PMID- 9005234
TI  - [Middle ear abnormalities in Klippel-Feil syndrome].
AB  - Klippel-Feil syndrome is characterized by a short-neck and a low occipital
      hairline due to such deformaties of the cervical spine as aplasia, dysplasia and
      fusions of the cervical and thoracic vertebrae. Approximately 1/3 of cases have
      sensorineural deafness, although occasional unilateral or bilateral conductive
      hearing loss due to middle ear malformations have been described. We have now
      treated two cases with unilateral middle ear malformations in patients with known
      Klippel-Feil syndrome. In the first case a completely malformed stapes was found
      as well as an atypical course of the facial nerve, which was found to be exactly
      over an absent oval window. In the second case aplasia of the stapes was seen and
      the oval and round windows were absent. No epitympanum was identifiable and a
      compact mastoid was found. In addition to audiometry, high-resolution CT was
      indispensable in diagnosis. However, surgical procedures in cases with unilateral
      middle ear deformations should be performed only on explicit request of the
      patient and not before the age of 16.

PMID- 9005235
TI  - [Self-induced illness in ENT medical practice. Artefacts as a contribution to
      differential diagnosis of unusual illness courses].
AB  - Until now reports of factitious disease have not been found in the ENT
      literature. In contrast, the dermatologic literature estimates an incidence from
      0.01 to 0.26%. In order to achieve effective treatment for these patients,
      knowledge of the characteristic symptoms is fundamental. The present paper
      describes the variety of disease possible, using three cases treated between 1992
      and 1994 in the ENT Department of Cologne. According to the literature, females
      are involved in a ratio of 9:1, with the majority working in medically related
      professions. Depression and anorexia are typical symptoms. When a factitious
      disease is suspected, psychiatric consultation is essential. Confrontation of a
      suspect patient by the otolaryngologist is not often considered because several
      reports quote suicidal behavior in up to 25% of self-manipulating patients and
      tendencies to refuse to follow psychiatric treatment are considerable.

PMID- 9005236
TI  - [Doppler ultrasound imaging of cerebral arteries].

PMID- 9005237
TI  - [Medicolegal implications in the angiologic practice and in the case of vascular
      trauma].

PMID- 9005238
TI  - [Forensic medical implications of vascular injuries in orthopedic surgery].
AB  - The vascular risk in orthopedic surgery results from the close relation between
      bones and vessel-nerve bundles, the use of sharp cutting and perforating
      instruments and, in hip surgery, the use of cement. The two main prognosis
      factors are early diagnosis and the time of treatment. Here we review risks by
      localizations. For spinal surgery, the great vessels may be damaged by discetomy
      and can lead to intraperitoneal bleeding and death or arteriovenous
      fistulization. In the scapular area, pin migrations after surgery involving the
      clavicle can lead to bleeding or false aneurysms of the subclavian artery. When
      surgery is performed for thoraco-brachial outlet syndromes, arterial damage is
      less frequent than nerve damage which can lead to death (one case reported) or
      severe sequelae. Hip surgery can damage the iliac or femoral vessels with severe
      sequelae after total hip replacement. Two cases of death related to femoral neck
      fracture and anticoagulant treatment are reported. Two other cases of lesions to
      the femoral artery with severe sequelae after treatment of diaphyseal fractures
      of the femur are also reported. In the knee area, consequences of surgery can be
      particularly severe, especially unrecognized damage or incorrect treatment of the
      popliteal artery after osteoarticular injuries, or iatrogenic lesions after knee
      surgery. Finally two cases of tibial artery lesions are reported. In most of
      these cases, medicolegal consequences were confirmed by court judgements.

PMID- 9005239
TI  - [Forensic medical implications of vascular injuries and accidents related to the
      practice of conventional vascular surgery].
AB  - Three areas are covered: neck surgery, thoracic aorta and abdominal aorta
      surgery. In neck surgery, cerebral vascular events can occur after endarterectomy
      of the carotid artery or after resection of carotid loops. These accidents are
      also seen after locoregional anesthesia in carotid surgery. Cases of hemorrhage
      or cerebral vascular events after chemodectomy are also reported. In thoracic
      aorta surgery, three cases of paraplegia after exeresis are reported. In
      abdominal aorta surgery, a case of non operation for aneurysm of the aorta led to
      legal procedures as did a case of an infected prosthesis. Legal procedures are
      rare after surgery of the lower limb arteries, despite the frequency of this
      surgery, but the observations reported demonstrate that amputations may follow an
      unfavorable course. Focus is increasingly being put on the need to inform the
      patient before surgery.

PMID- 9005240
TI  - [Forensic medical implications of vascular injuries and accidents related to the
      practice of conventional general surgery].
AB  - We recall a certain number of cases in our experience after cure of a hernia.
      Cases include damage to the iliac arteries and veins after appendicectomy (the
      case is still in court 25 years after the accident), hemorrhage after
      hysterectomy, damage to the iliac artery due to a Pfannensteel incision, lesion
      of the axillary artery during lymph node curettage, and hemorrhage during
      attempted appendicectomy.

PMID- 9005241
TI  - [Forensic medical implications of vascular injuries in the course of video
      endoscopic surgery].
AB  - We report 21 case files. Seven concerned gynecology laparoscopy with 3 deaths and
      4 severe sequelae. Five cases involved laparoscopic appendicectomy with 1 death
      and 4 severe sequelae. In 3 cases complications during conventional
      appendicectomy were treated laparoscopically. Three cases concerned post
      operative complications and finally, 6 cases of laparoscopic cholecystectomy are
      reported, including 4 fatal cases. Three-fourths of these cases occurred after
      1990 and the fatal cases were usually related to bleeding caused by the inflation
      trocar, emphasizing the importance of strict safety measures, especially control
      of intraabdominal pressure and verification of ligatures. These case-files
      demonstrate that severe vascular events can occur in all laparoscopic procedures.
      In most of the cases, the surgeon was not unexperienced but rather well trained
      in this type of surgery. Practicians using this technique must have training in
      vascular surgery or at least operate within structures allowing immediate relay
      by a vascular surgeon.

PMID- 9005242
TI  - [Forensic medical implications in the course of sclerotherapy of varicose veins].
AB  - Complications are exceptional compared to the number of sclerosis treatments
      performed. We report 58 case-files with medico-legal implications. Intraarterial
      injections are by far the most severe complications: we observed 40 such cases
      with the following consequences: 7 major amputations including 2 above the knee
      and 5 below the knee, 6 minor peripheral amputations of one or more toes, 27
      severe sequelae, mainly due to retraction of the triceps sural muscle. This type
      of accident occurs more readily after attempted sclerosis of the lesser saphenous
      vein "crosse", although other localizations can be involved: inguinal area by
      sclerosis of the greater saphenous vein "crosse", the lower third of the leg with
      direct injection into the anterior or posterior tibial artery or its branches.
      Subcutaneous injections of the sclerosis agent produce either simple inflammatory
      reactions or skin necrosis. Neurological disorders can be observed by direct
      damage to the nerve. Sensorial complications may occur by lesion of a cutaneous
      branch of the popliteal sciatic nerve. Other cases involve motor disorders.
      Pulmonary thromboembolic events (4 cases) appear to be exception when modern
      criteria for the diagnosis of phlebitis are used. General allergic and
      anaphylactic reactions are very rare and often related to overdose. The same is
      true for toxic reactions. One case of septicemia occurred after incision of post
      sclerosis clots. From a medicolegal point of view, the responsibility of the
      practician is usually confirmed for severe accidents (intraarterial injections)
      leading to trophic disorders. For necrosis or limited eschars, the question is
      debated.

PMID- 9005243
TI  - [Forensic medical implications in surgery of chronic venous insufficiency of the
      legs].
AB  - Current literature and personal experience with these complications are
      discussed. Complications with medicolegal implications have been analyzed in
      three studies, in France by J. Natali and A. Rispoli (Marseille, 1994) and in
      Great Britain by W.G. Tennant and C.V. Ruckley. The incidences reported are
      certainly underestimated as only those complications leading to an official
      expert opinion were counted. We also report our personal experience with
      medicolegal implications after 15,340 limb operations performed from 1968 to
      1994. The conclusions provide an overall view of how to reduce the number of
      complications and provide adequate therapeutic management.

PMID- 9005244
TI  - [Forensic medical implications of vascular punctures and catheterization and
      radiologic procedures with diagnostic or therapeutic purpose].
AB  - Whatever the aim of the procedure, puncture of a vessel can lead to local
      complications. Access to the artery carries a risk of hemorrhage, occlusion,
      stenosis, arteriovenous fistulization or pseudo-aneurysm. The same types of
      complications can occur in veins. Other complications include skin necrosis due
      to extravasation of the contrast medium, perforation of the superior vena cava
      after insertion of an infusion catheter and the risk of pericardial effusion.
      General complications occur immediately, usually caused by contrast media, or
      late. There are different examples of secondary legal procedures following
      punctures involving, with the exception of radiology cases, intraarterial
      injection at the elbow, perforation of the right atrium by a jugular catheter and
      acute ischemia of the foot after catheterization of the pedial artery. Legal
      procedures after radiological procedures were discussed in more detail. The
      personal experience of the authors and others concerns accidents occurring after
      arteriography, angioplasty or embolization. Finally, two legal cases after
      treatment for impotency are analyzed. We focus on a certain number of rules on
      patient information, preangiography consultation, participation of an
      anesthetist, careful post-operative follow-up and operation report. Finally, the
      possibility of radiation-induced arteriopathy is demonstrated by one case
      reported here.

PMID- 9005245
TI  - [Forensic medical implications of lymph node and lymphatic injuries].
AB  - Three cases of injuries to lymph nodes are reported; the main sequela was
      lymphedema. One case occurred after node curettage and two after varicose vein
      surgery.

PMID- 9005246
TI  - [Forensic medical implications of anticoagulant treatments].
AB  - Several types of accidents related to anticoagulant treatment can lead to legal
      procedures, including: thromboembolic post-operative complications associated
      with lack of anticoagulant prophylaxis and leading to sequelae or death; severe
      hemorrhagic or thromboembolic accidents attributed to poor management of
      anticoagulant therapy; complications with sequelae or death resulting from
      heparin-induced thrombopenia, either with standard or low-molecular weight
      heparin and associated with poor surveillance of platelet counts. The exceptional
      nature of accidents leading to legal procedures (24 legal cases in Pr Natali's
      experience) and the small number of other cases reported should not lead to
      underestimating the importance of precise rules for anticoagulation treatments.
      In 7 cases, there was no anticoagulant prophylaxis after surgery. Recent
      consensus conferences have proposed a definition of small, moderate or high risk
      of thrombosis as a function of patient status and surgical procedure. Expert
      working groups have defined the operated patients for which pharmacological anti
      coagulation is necessary. In 19 other cases, management of the treatment protocol
      was insufficient leading to severe hemorrhage with sequelae, severe
      thromboembolism, or late diagnosis of heparin-induced thrombocytopenia because of
      insufficient surveillance of platelet counts. Recent advances in laboratory tests
      for the diagnosis of heparin-induced thrombocytopenia should be emphasized. To
      these case reports can be added other observations in a small number of
      complaints resulting from unadvisable treatment combinations, poor surveillance
      of a thromboembolic event or dangerous invasive exploration.

PMID- 9005247
TI  - [Legal aspects of vascular injuries and their forensic medical sequelae].
AB  - The questions which an expert opinion should answer are presented in the first
      part of this article: evaluation of the physical or functional handicap,
      evaluation of the occupational handicap, analysis of any cause and effect between
      the trauma and the arterial injury. Four criteria are studied: the former status
      of the patient, the nature of the injury, the time of onset of the signs or delay
      to onset of disorders, and certain diagnosis. The second part of the article
      concerns the general methodology used in vascular injuries. In the third part
      professional responsibility is discussed-three conditions, and all three, are
      necessary for malpractice to be retained: 1) Prejudice or harm to the patient, 2)
      Error committed by the practitioner, 3) A causal relationship between the error
      and the verified harm. The four levels of medical responsibility are recalled:
      penal, civil, administrative and ordinal. Finally the physician's management of
      vascular injuries can also lead to legal pursuits.

PMID- 9005248
TI  - An unusual cause for lumbar radiculopathy: a synovial facet joint cyst of the
      right L5 joint.
AB  - OBJECTIVE: To report a rare cause of lumbar radiculopathy. CLINICAL FEATURES: A
      72-yr-old man suffered from pain that radiated down the posterior thigh and calf
      for 3 wk. The right foot and first toe extensors were weak and sensation was
      decreased over the dorsum of the foot. Straight leg raising was positive at 50
      degrees on the right. Computed tomography with contrast revealed a large cyst
      with focal vacuum change with displacement of the dural sac at the L4-5 level.
      INTERVENTION AND OUTCOME: An L4-5 laminectomy and facetectomy was performed with
      relief of the patient's complaint. The patient resumed full activity at 3 months.
      CONCLUSION: An unusual cause of an L5 radiculopathy is discussed. Of the reported
      cases, surgical intervention has been the treatment of choice. Conservative
      treatment, including injections with corticosteroids and chiropractic management,
      have been reported to be successful. Further investigations using controls are
      needed to determine if conservative care is more cost-effective than surgical
      intervention.

PMID- 9005249
TI  - Induction of murine acquired immunodeficiency syndrome (MAIDS) in allophenic mice
      generated from strains susceptible and resistant to disease.
AB  - To examine whether a retroviral disease can be controlled in animals in which
      cells from a resistant strain coexist in a state of immunological tolerance with
      cells from a susceptible strain, allophenic mice were constructed and infected
      with LP-BM5 murine leukemia viruses which induce a fatal disorder, termed murine
      acquired immunodeficiency syndrome (MAIDS), characterized by lymphoproliferation
      and immunodeficiency in susceptible inbred strains of mice. We found that in two
      different strain combinations, resistance to MAIDS was contingent on the presence
      in individual animals of >50% of lymphocytes of resistant strain origin and
      correlated with reduction or elimination of retrovirus. In contrast, animals
      harboring substantial, but less than predominant, numbers of genetically
      resistant lymphocytes developed disease and died within the same time frame as
      susceptible control mice with uncontained proliferation of retrovirus.

PMID- 9005250
TI  - Ceramics in dentistry: historical roots and current perspectives.
AB  - This article presents a brief history of dental ceramics and offers perspectives
      on recent research aimed at the further development of ceramics for clinical use,
      at their evaluation and selection, and very importantly, their clinical
      performance. Innovative ceramic materials and ceramics processing strategies that
      were introduced to restorative dentistry since the early 1980s are discussed.
      Notable research is highlighted regarding (1) wear of ceramics and opposing
      enamel, (2) polishability of porcelains, (3) influence of firing history on the
      thermal expansion of porcelains for metal ceramics, (4) machining and CAD/CAM as
      fabrication methods for clinical restorations, (5) fit of ceramic restorations,
      (6) clinical failure mechanisms of all-ceramic prostheses, (7) chemical and
      thermal strengthening of dental ceramics, (8) intraoral porcelain repair, and (9)
      criteria for selection of the various ceramics available. It is found that strong
      scientific and collaborative foundations exist for the continued understanding
      and improvement of dental ceramic systems.

PMID- 9005251
TI  - The impact of dementia on the sufferer and available treatment interventions: an
      overview.
AB  - An overview of the psychological and behavioral consequences of dementia on
      sufferers is provided. Psychological interventions for improving the quality of
      life of patients, difficulties of diagnosis, the role of general practitioners,
      and th contribution of psychologists in the management of dementia are discussed.

PMID- 9005253
TI  - The relationship between age and gender in workers' attitudes toward sexual
      harassment.
AB  - The relationship between gender, age, and workers' attitudes toward sexual
      harassment as measured by the Sexual Harassment Attitudes Scale was examined.
      Participants were full-time workers employed at a local hardware-manufacturing
      company or a local utility company in New England. Results indicated that the
      women younger than 40 years old were significantly less tolerant of sexual
      harassment than older women were. In contrast, male workers' tolerance of sexual
      harassment decreased with age up until the age of 50 years, after which their
      tolerance level of sexual harassment increased significantly.

PMID- 9005252
TI  - Do homosexual teachers pose a risk to pupils?
AB  - Questionnaires were completed by 5,182 adults derived from one-wave area cluster
      samples in 6 metropolitan areas: 56% of homosexuals and 18% of heterosexuals
      reported having had a homosexual teacher, 12% of the men and 4% of the women said
      that the teacher made sexual advances toward them. A fifth of those with a
      homosexual teacher said they were influenced to regard homosexuality as socially
      acceptable; 4% said that the teacher influenced them to try homosexuality. About
      1% of the sample reported that, as pupils, they had sexual relations with at
      least one of their elementary or secondary teachers. Eight respondents reported
      their first sexual experience was with an elementary or secondary teacher and
      that one of these experiences was homosexual. Of 49 other reported sexual
      experiences with teachers, 12 were homosexual. The findings that homosexuals more
      frequently claimed to have had homosexual teachers and more frequently reported
      homosexual sex with teachers tend to fit the contagion model of homosexuality-
      that homosexuality is taught by or caught by sexual interaction with homosexual
      practitioners.

PMID- 9005254
TI  - Attitudes toward health risks and sunbathing behavior.
AB  - Sunbathing confers the benefits of looking and feeling good but presents the long
      term risk of skin cancer. In a disguised experiment exploring attitudes toward
      sunbathing by British adults, participants were asked to rate their willingness
      to take a hypothetical new drug (with different levels of risk) that would make
      them look and feel good. One aspect of the resulting risk profiles was
      significantly related to a positive attitude to open-air sunbathing but not to
      sunbed use, possibly because it was erroneously thought that using a sunbed is
      not risky. The well-established finding that women are more cautious was
      confirmed; the risk function for men was curvilinear, in contrast to women, who
      were willing to increase their risk linearly over their lifetime.

PMID- 9005255
TI  - Indole inhibitors of human nonpancreatic secretory phospholipase A2. 1. Indole-3
      acetamides.
AB  - Phospholipases (PLAs) produce rate-limiting precursors in the biosynthesis of
      various types of biologically active lipids involved in inflammatory processes.
      Increased levels of human nonpancreatic secretory phospholipase A2 (hnps-PLA2)
      have been detected in several pathological conditions. An inhibitor of this
      enzyme could have therapeutic utility. A broad screening program was carried out
      to identify chemical structures which could inhibit hnps-PLA2. One of the lead
      compounds generated by the screening program was 5-methoxy-2-methyl-1
      (phenylmethyl)-1H-indole-3-acetic acid (13a). We describe the syntheses,
      structure--activity relationships, and pharmacological activities of a series of
      indole-3-acetamides and related compounds derived from this lead. This SAR was
      undertaken with the aid of X-ray crystal structures of complexes between the
      inhibitors and hnps-PLA2 which were of great value in directing the SAR.

PMID- 9005256
TI  - Commentary on the growth of renal calculi.

PMID- 9005258
TI  - Organizations of medical interest.

PMID- 9005257
TI  - International conference on Peyronie's disease. Advances in basic and clinical
      research. March 17-19, 1993.

PMID- 9005259
TI  - Health reform for the 21st century? It may have to wait until the 21st century.
AB  - OBJECTIVES: To assess the likelihood of health care legislation in the
      forthcoming 105th Congress in 5 areas: health care coverage, tax and Employee
      Retirement Income Security Act (ERISA) policy, Medicaid, Medicare, and managed
      care. DESIGN: Informal, semistructured conversations that took place in the
      months prior to the 1996 elections. POPULATION: Congressional health staff and
      administration officials. OUTCOME MEASURES: Unofficial, off-the-record personal
      opinions. RESULTS: Health care coverage initiatives to benefit children and
      unemployed persons are likely to be proposed, but have little chance of
      enactment; children are seen as well provided for under current Medicaid law, the
      strong economy and high employment levels lower concern for unemployed issues,
      and the effort required to pass the Kassebaum-Kennedy legislation needs time to
      settle. Tax proposals, such as medical savings accounts (MSAs), and ERISA
      amendments have no constituency; also, the MSA demonstration in Kassebaum-Kennedy
      will forestall further action. Medicaid is far less an issue than in the previous
      Congress, because spending has fallen unexpectedly, the bitter fight over block
      grants makes them unlikely to be revisited, and the administration is likely to
      enhance state flexibility through waivers. Medicare will be the subject of
      substantial action to defer impending insolvency temporarily, but there is
      virtually no chance that definitive long-term solutions will be enacted even
      though the underlying fiscal problems are thoroughly understood and recognized.
      Managed care will be the venue for numerous proposals designed to address
      specific consumer and quality issues. CONCLUSIONS: Four bitter years of fighting
      over health care issues has raised awareness of the problems, but has produced a
      political chemistry that is too rancorous to permit passage of significant
      legislation in the near future.

PMID- 9005261
TI  - Revised guidelines for managing acute MI.

PMID- 9005260
TI  - New era for acute stroke treatment.

PMID- 9005263
TI  - Elevated lipoprotein(a) and premature coronary heart disease.

PMID- 9005262
TI  - From the Centers for Disease Control and Prevention. Immunization of adolescents.
      Recommendations of the Advisory Committee on Immunization Practices, the American
      Academy of Pediatrics, the American Academy of Family Physicians, and the
      American Medical Association.

PMID- 9005264
TI  - Elevated lipoprotein(a) and premature coronary heart disease.

PMID- 9005265
TI  - Elevated lipoprotein(a) and premature coronary heart disease.

PMID- 9005266
TI  - Famciclovir for genital herpes.

PMID- 9005267
TI  - Use of glycosylated hemoglobin levels for diagnosing diabetes mellitus.

PMID- 9005268
TI  - The last refreshing taste.

PMID- 9005269
TI  - A 61-year-old man with Parkinson's disease, 1 year later.

PMID- 9005270
TI  - Patients, primary care physicians, and payments for hospital visits.

PMID- 9005271
TI  - Is there a Gulf War Syndrome? Searching for syndromes by factor analysis of
      symptoms.
AB  - OBJECTIVE: To search for syndromes in Persian Gulf War veterans. PARTICIPANTS:
      Two hundred forty-nine (41%) of the 606 Gulf War veterans of the Twenty-fourth
      Reserve Naval Mobile Construction Battalion living in 5 southeastern states
      participated; 145 (58%) had retired from service, and the rest were still serving
      in the battalion. DESIGN: Participants completed a standardized survey booklet
      measuring the anatomical distributions or characteristics of each symptom, a
      booklet measuring wartime exposures, and a standard psychological personality
      assessment inventory. Two-stage factor analysis was used to disentangle ambiguous
      symptoms and identify syndromes. MAIN OUTCOME MEASURES: Factor analysis-derived
      syndromes. RESULTS: Of 249 participants, 175 (70%) reported having had serious
      health problems that most attributed to the war, and 74 (30%) reported no serious
      health problems. Principal factor analysis yielded 6 syndrome factors, explaining
      71% of the variance. Dichotomized syndrome indicators identified the syndromes in
      63 veterans (25%). Syndromes 1 ("impaired cognition," characterized by problems
      with attention, memory, and reasoning, as well as insomnia, depression, daytime
      sleepiness, and headaches), 2 ("confusion-ataxia," characterized by problems with
      thinking, disorientation, balance disturbances, vertigo, and impotence), and 3
      ("arthro-myo-neuropathy," characterized by joint and muscle pains, muscle
      fatigue, difficulty lifting, and extremity paresthesias) represented strongly
      clustered symptoms; whereas, syndromes 4 ("phobia-apraxia"), 5 ("fever
      adenopathy"), and 6 ("weakness-incontinence") involved weaker clustering and
      mostly overlapped syndromes 2 and 3. Veterans with syndrome 2 were 12.5 times
      (95% confidence interval, 3.5-44.8) more likely to be unemployed than those with
      no health problems. A psychological profile, found in 48.4% of those with the
      syndromes, differed from posttraumatic stress disorder, depression, somatoform
      disorder, and malingering. CONCLUSION: These findings support the hypothesis that
      clusters of symptoms of many Gulf War veterans represent discrete factor analysis
      derived syndromes that appear to reflect a spectrum of neurologic injury
      involving the central, peripheral, and autonomic nervous systems.

PMID- 9005272
TI  - Evaluation of neurologic function in Gulf War veterans. A blinded case-control
      study.
AB  - OBJECTIVE: To determine whether Gulf War-related illnesses are associated with
      central or peripheral nervous system dysfunction. DESIGN: Nested case-control
      study. PARTICIPANTS: Twenty-three veterans with factor analysis-derived syndromes
      (the cases), 10 well veterans deployed to the Gulf War (the deployed controls),
      and 10 well veterans not deployed to the Gulf War (the nondeployed controls).
      METHOD: With investigators blinded to group identities, participants underwent
      objective neurophysiological, audiovestibular, neuroradiological,
      neuropsychological, and blood tests. MAIN OUTCOME MEASURES: Evidence of
      neurologic dysfunction. RESULTS: Compared with the 20 controls, the 23 cases had
      significantly more neuropsychological evidence of brain dysfunction on the
      Halstead Impairment Index (P=.01), greater interside asymmetry of the wave I to
      wave III interpeak latency of brain stem auditory evoked potentials (P=.02),
      greater interocular asymmetry of nystagmic velocity on rotational testing,
      increased asymmetry of saccadic velocity (P=.04), more prolonged interpeak
      latency of the lumbar-to-cerebral peaks on posterior tibial somatosensory evoked
      potentials (on right side, P=.03, and on the left side, P=.005), and diminished
      nystagmic velocity after caloric stimulation bilaterally (P values range from .02
      to .04). Cases (n=5) with syndrome 1 ("impaired cognition") were the most
      impaired on brain stem auditory evoked potentials (P=.005); those (n=13) with
      syndrome 2 ("confusion-ataxia") were the most impaired on the Halstead Impairment
      Index (P=.006), rotational testing (P=.01), asymmetry of saccadic velocity
      (P=.03), and somatosensory evoked potentials (P< or =.01); and those (n=5) with
      syndrome 3 ("arthro-myo-neuropathy") were the most impaired on caloric
      stimulation (P< or =.01). CONCLUSIONS: The 3 factor-derived syndromes identified
      among Gulf War veterans appear to represent variants of a generalized injury to
      the nervous system.

PMID- 9005273
TI  - Self-reported exposure to neurotoxic chemical combinations in the Gulf War. A
      cross-sectional epidemiologic study.
AB  - OBJECTIVE: To identify risk factors of factor analysis-derived Gulf War-related
      syndromes. DESIGN: A cross-sectional survey. PARTICIPANTS: A total of 249 Gulf
      War veterans from the Twenty-fourth Reserve Naval Mobile Construction Battalion.
      DATA COLLECTION: Participants completed standardized booklets measuring self
      reported wartime exposures and present symptoms. MAIN OUTCOME MEASURES:
      Associations of factor analysis-derived syndromes with risk factors for chemical
      interactions that inhibit butyrylcholinesterase and neuropathy target esterase.
      RESULTS: Risk of syndrome 1 ("impaired cognition") was greater in veterans who
      reported wearing flea collars during the war (5 of 20, 25%) than in those who
      never wore them (7 of 229, 3%; relative risk [RR], 8.7; 95% confidence interval
      [CI], 3.0-24.7; P<.001). Risk of syndrome 2 ("confusion-ataxia") increased with a
      scale of advanced adverse effects from pyridostigmine bromide (chi2 for trend,
      P<.001), was greater among veterans who believed they had been involved in
      chemical weapons exposure (18 of 108, 17%) than in those who did not (3 of 141,
      2%; RR, 7.8; 95% CI, 2.3-25.9; P<.001), and was increased in veterans who had
      been in a sector of far northeastern Saudi Arabia on the fourth day of the air
      war (6 of 21, 29%) than in those who had not been (15 of 228, 7%; RR, 4.3; 95%
      CI, 1.9-10.0; P=.004). Effects of perceived chemical weapons exposure and
      advanced adverse effects from pyridostigmine were synergistic (Rothman S, 5.3;
      95% CI, 1.04-26.7). Risk of syndrome 3 ("arthro-myo-neuropathy") increased with
      an index of frequency and amount of government-issued insect repellent containing
      75% DEET (N,N-diethyl-m-toluamide) in ethanol applied during the war (chi2 for
      trend, P<.001) and with advanced adverse effects from pyridostigmine (chi2 for
      trend, P<.001). CONCLUSION: Some Gulf War veterans may have delayed, chronic
      neurotoxic syndromes from wartime exposure to combinations of chemicals that
      inhibit butyrylcholinesterase and neuropathy target esterase.

PMID- 9005274
TI  - Self-reported illness and health status among Gulf War veterans. A population
      based study. The Iowa Persian Gulf Study Group.
AB  - OBJECTIVE: To assess the prevalence of self-reported symptoms and illnesses among
      military personnel deployed during the Persian Gulf War (PGW) and to compare the
      prevalence of these conditions with the prevalence among military personnel on
      active duty at the same time, but not deployed to the Persian Gulf (non-PGW).
      DESIGN: Cross-sectional telephone interview survey of PGW and non-PGW military
      personnel. The study instrument consisted of validated questions, validated
      questionnaires, and investigator-derived questions designed to assess relevant
      medical and psychiatric conditions. SETTING: Population-based sample of military
      personnel from Iowa. STUDY PARTICIPANTS: A total of 4886 study subjects were
      randomly selected from 1 of 4 study domains (PGW regular military, PGW National
      Guard/Reserve, non-PGW regular military, and non-PGW National Guard/Reserve),
      stratifying for age, sex, race, rank, and branch of military service. MAIN
      OUTCOME MEASURES: Self-reported symptoms and symptoms of medical illnesses and
      psychiatric conditions. RESULTS: Overall, 3695 eligible study subjects (76%) and
      91% of the located subjects completed the telephone interview. Compared with non
      PGW military personnel, PGW military personnel reported a significantly higher
      prevalence of symptoms of depression (17.0% vs 10.9%; Cochran-Mantel-Haenszel
      test statistic, P<.001), posttraumatic stress disorder (PTSD) (1.9% vs 0.8%,
      P=.007), chronic fatigue (1.3% vs 0.3%, P<.001), cognitive dysfunction (18.7% vs
      7.6%, P<.001), bronchitis (3.7% vs 2.7%, P<.001), asthma (7.2% vs 4.1%, P=.004),
      fibromyalgia (19.2% vs 9.6%, P<.001), alcohol abuse (17.4% vs 12.6%, P=.02),
      anxiety (4.0% vs 1.8%, P<.001), and sexual discomfort (respondent, 1.5% vs 1.1%,
      P=.009; respondent's female partner, 5.1% vs 2.4%, P<.001). Assessment of health
      related quality of life demonstrated diminished mental and physical functioning
      scores for PGW military personnel. In almost all cases, larger differences
      between PGW and non-PGW military personnel were observed in the National
      Guard/Reserve comparison. Within the PGW military study population, compared with
      veterans in the regular military, veterans in the National Guard/Reserve only
      reported more symptoms of chronic fatigue (2.9% vs 1.0%, P=.03) and alcohol abuse
      (19.4% vs 17.0%, P=.004). CONCLUSIONS: Military personnel who participated in the
      PGW have a higher self-reported prevalence of medical and psychiatric conditions
      than contemporary military personnel who were not deployed to the Persian Gulf.
      These findings establish the need to further investigate the potential etiologic,
      clinical, pathogenic, and public health implications of the increased prevalence
      of multiple medical and psychiatric conditions in populations of military
      personnel deployed to the Persian Gulf.

PMID- 9005275
TI  - Building a national strategy for the prevention and management of and research in
      chronic obstructive pulmonary disease. National Heart, Lung, and Blood Institute
      Workshop Summary. Bethesda, Maryland, August 29-31, 1995.

PMID- 9005276
TI  - Evaluation of a system using oral mucosal transudate for HIV-1 antibody screening
      and confirmatory testing. OraSure HIV Clinical Trials Group.
AB  - OBJECTIVE: To determine accuracy of a human immunodeficiency virus type 1 (HIV-1)
      antibody testing system using a device to collect and stabilize oral mucosal
      transudate (OMT), a fluid with increased levels of IgG; an enzyme immunoassay
      (EIA) screening test optimized for OMT; and a Western blot confirmatory test
      designed for use with OMT. DESIGN: The OMT specimens were tested by EIA and, if
      indicated, confirmatory Western blot according to a standard testing algorithm.
      The OMT results were compared with true HIV status as determined by serum testing
      and/or clinical diagnosis. PATIENTS: Specimens from 3570 subjects (2382 at low
      risk, 698 at high risk, 242 with acquired immunodeficiency syndrome [AIDS], and
      248 "nonspecificity" [persons with diseases associated with an increased
      frequency of false-positive results in HIV testing]) were collected at 11
      geographically diverse sites (including blood banks, public health clinics,
      general medical clinics, HIV clinics, sexually transmitted disease clinics, and a
      hemophilia center) in the United States. MAIN OUTCOME MEASURES: Overall accuracy
      of testing OMT for HIV-1 antibodies compared with true HIV-1 antibody status;
      sensitivity and specificity of OMT EIA and Western blot. RESULTS: Sensitivity of
      OMT EIA testing in 673 true-positive subjects was 99.9% (672/673). The OMT
      Western blot results in the 673 true-positive subjects were positive in 665 and
      indeterminate in 8. The EIA followed by Western blot (if EIA was repeatedly
      reactive) yielded a negative result in 99.9% (2893/2897) of OMT samples from true
      negatives and an indeterminate result in 4. The OMT testing system provided the
      correct result or would trigger appropriate follow-up testing in 3569 (>99.9%) of
      3570 cases. CONCLUSION: HIV-1 antibody testing of OMT samples is a highly
      accurate alternative to serum testing.

PMID- 9005278
TI  - [Proceedings:The 2nd Japanese-United States vancomycin forum (discussion)].

PMID- 9005277
TI  - Illness in Gulf War veterans. Causes and consequences.

PMID- 9005279
TI  - The Mayo Ventilator-Dependent Rehabilitation Unit: a 5-year experience.
AB  - OBJECTIVE: To describe the outcomes of 206 patients admitted to the Mayo
      Ventilator-Dependent Rehabilitation Unit (VDRU) during a 5-year study period.
      DESIGN: We analyze the patient data for 1990 through 1994, which had been
      prospectively entered into a computer database for a cohort of 206 patients who
      had become ventilator dependent during their current hospitalization. MATERIAL
      AND METHODS: Patients in the VDRU were classified into one of six categories that
      reflected the reasons for ventilator dependence. Ability to be weaned from
      mechanical ventilation, duration of hospital stay and ventilator dependence,
      outcome, disposition, demographics, and long-term survival were analyzed. The
      VDRU patient group was compared for hospital and follow-up outcomes with a group
      of historical control patients previously described by us. RESULTS: The Mayo VDRU
      was established in January 1990. During the first 5 years of its operation, 206
      newly ventilator-dependent patients were admitted to the VDRU, 190 (92%) of whom
      survived to be dismissed; 16 patients (8%) died in the hospital. Of the 190
      patients dismissed, 77% were able to return to their homes. Overall, 153 patients
      were liberated from mechanical ventilation, whereas 37 remained either completely
      or partially ventilator dependent. Of these 37 patients, 27 (73%) were receiving
      nocturnal mechanical ventilation only. The 4-year survival was 53%. CONCLUSION:
      The Mayo VDRU has been highly successful in liberating newly ventilator-dependent
      patients from mechanical ventilation. The long-term survival after management in
      the VDRU has been excellent. In addition, the medical charges for care in the
      VDRU are less than intensive-care unit charges.

PMID- 9005280
TI  - Effect of intraoperative anesthetic events on postoperative patient satisfaction.
AB  - OBJECTIVE: To assess overall perioperative and anesthetic care-specific patient
      satisfaction. DESIGN: We mailed questionnaires postoperatively to three groups of
      surgical patients (those who underwent anesthesia without complications, those
      who experienced airway management difficulties, and those who had cardiovascular
      perturbations) and analyzed the responses. MATERIAL AND METHODS: All patients 18
      to 75 years of age who underwent hospital-based surgical procedures in our acute
      care hospitals during the interval from January to September 1993 were eligible
      for this investigation. We asked a total of 315 patients--105 in each of the
      three study groups--about their satisfaction with perioperative care. Specific
      positive or negative comments that the patients returned in their questionnaires
      were tabulated into the following sub-categories: physician, nurse, technique,
      time, and institution concerns. RESULTS: Of the 315 questionnaires sent to
      patients, 239 (75.9%) were returned. No difference in overall patient
      satisfaction (defined as very satisfied or a combination of very satisfied and
      satisfied) was noted among the groups. No patients identified themselves as
      dissatisfied or very dissatisfied with their overall care, although a small
      percentage expressed dissatisfaction because of time delays. The specific patient
      comments suggested that the positive interactions with physicians and nurses
      outweighed the concerns about time delays. CONCLUSION: This study showed that
      intraoperative anesthetic events did not affect patient satisfaction.
      Interactions with physicians and nurses dominated the decision about patient
      satisfaction, and time delays were the most frequently cited negative comment.

PMID- 9005281
TI  - Isolated noncompaction of the myocardium in adults.
AB  - OBJECTIVE: To describe the entity of isolated ventricular noncompaction (IVNC)
      and present a series of cases of this rare disorder in an adult population.
      MATERIAL AND METHODS: We review a 10-year experience with the diagnosis of IVNC
      and discuss the clinical, echocardiographic, and pathologic features of this
      condition. Echocardiographic diagnostic criteria included the absence of
      coexisting cardiac abnormalities, the presence of prominent and excessive
      trabeculations of one or more ventricular wall segments, and intertrabecular
      spaces perfused from the ventricular cavity. Pathologic examination focused on
      regions with exaggerated trabeculations and deep intertrabecular spaces. RESULTS:
      IVNC is an unexplained arrest of myocardial morphogenesis previously encountered
      mainly in pediatric patients. Among 37,555 transthoracic echocardiographic
      studies performed at our hospital between January 1984 and October 1993, 17 cases
      of IVNC were identified in adult subjects (14 men and 3 women, 18 to 71 years of
      age). The mean time from onset of symptoms to correct diagnosis was 3.5 +/- 5.7
      years, and the mean duration of follow-up was 30 +/- 28 months. Common clinical
      symptoms were heart failure, ventricular arrhythmias, and a history of embolic
      events. Two-dimensional echocardiography revealed 10 patients with left
      ventricular and 7 (41%) with biventricular IVNC. During a 6-year follow-up
      period, eight patients died and two underwent heart transplantation. CONCLUSION:
      Although the diagnosis of IVNC in an adult population is often delayed because of
      similarities with more frequently diagnosed conditions, two-dimensional
      echocardiography will facilitate the diagnosis of IVNC in this subset of
      patients. Because of the high incidence of heart failure, ventricular
      arrhythmias, and embolization in adults with IVNC, early diagnosis is important.

PMID- 9005282
TI  - Pioneers of mammography--Warren and Egan.

PMID- 9005283
TI  - Mycoplasma-associated pericarditis.
AB  - Mycoplasma pneumoniae-associated pericarditis may result in pronounced morbidity
      unless appropriate therapy is administered. In this report, we describe a patient
      who had recurrent episodes of chest pain, intermittent constitutional symptoms,
      and, eventually, cardiac tamponade due to pericarditis despite treatment with
      nonsteroidal anti-inflammatory drugs. Immunofluorescence antibody titers were
      consistent with recent M. pneumoniae infection, and antibiotic therapy resulted
      in rapid and complete resolution of the patient's symptoms. This treatable entity
      may be underrecognized and can now be diagnosed with sensitive serologic testing.

PMID- 9005284
TI  - Sarcoid masquerading as optic nerve sheath meningioma.
AB  - Sarcoid manifesting as an optic nerve tumor without evidence of systemic disease
      is uncommon. Throughout a 2-year period, a 22-year-old white woman had
      progressive monocular loss of vision to the level of no light perception. Optic
      atrophy but no uveitis was noted in the affected eye. Magnetic resonance imaging
      revealed thickening and enhancement of the apical optic nerve, with "tram
      tracking." The presumptive diagnosis was optic nerve sheath meningioma; however,
      a biopsy specimen from the optic nerve revealed sarcoid. Extensive postoperative
      investigations revealed no systemic sarcoidosis. To our knowledge, 17 cases
      similar to ours, with the diagnosis proved by optic nerve biopsy, have been
      previously reported in the English-language literature. Most of these were
      mistaken preoperatively for optic nerve sheath meningioma. None of the patients
      had evidence of systemic sarcoidosis on initial postoperative testing.
      Neuroimaging, serum level of angiotensin-converting enzyme, and clinical
      characteristics such as age, race, sex, and optochoroidal collaterals do not
      distinguish optic nerve sheath meningioma from sarcoid of the optic nerve. In the
      absence of uveitis or systemic involvement, optic nerve sarcoid manifesting as an
      orbital tumor is virtually impossible to diagnose without results of biopsy.

PMID- 9005285
TI  - Sir James Mackenzie's 1918 visit to Mayo.

PMID- 9005286
TI  - Hepatopulmonary syndrome with progressive hypoxemia as an indication for liver
      transplantation: case reports and literature review.
AB  - In the hepatopulmonary syndrome (HPS), a pulmonary vascular complication of liver
      disease, severe hypoxemia due to pulmonary vascular dilatation can be extremely
      debilitating. Determining whether patients with advanced liver disease and HPS
      should be considered for liver transplantation is difficult. We describe three
      patients with progressive and severe hypoxemia who underwent successful liver
      transplantation and had resolution of their arterial hypoxemia. In these
      patients, the progressive pulmonary deterioration accelerated the need and was
      considered an indication for liver transplantation rather than being considered
      an absolute or relative contraindication. In addition, we review the literature
      on 81 pediatric and adult patients with HPS who underwent liver transplantation
      and specifically highlight mortality, morbidity, syndrome resolution, and
      prognostic factors. Posttransplantation mortality (16%) was associated with the
      severity of hypoxemia (mean arterial oxygen tension [PaO2] in 68 survivors was
      54.2 +/- 13.2 mm Hg and in 13 nonsurvivors was 44.7 +/- 7.7 mm Hg; P<0.03).
      Patients with a pretransplantation PaO2 of 50 mm Hg or lower had significantly
      more frequent mortality (30%) in comparison with those with a PaO2 greater than
      50 mm Hg (4%; P<0.02). Pulmonary recommendations that address the severity of
      hypoxemia and candidacy for liver transplantation are discussed.

PMID- 9005287
TI  - Comparison of immediate and long-term outcome of coronary angioplasty performed
      for unstable angina and rest pain in men and women.
AB  - OBJECTIVE: To determine whether a sex-related difference in outcome is present
      among patients who undergo percutaneous transluminal coronary angioplasty (PTCA)
      for unstable angina. DESIGN: We retrospectively analyzed the results after PTCA
      was performed between January 1981 and June 1993 in a series of 2,073 men and 941
      women with unstable angina and rest pain. RESULTS: The success rates of PTCA were
      similar for women and men (87.9% and 87.2%, respectively), as were the in
      hospital mortality rates (4.1% and 3.2%, respectively) and the need for emergency
      coronary artery bypass operation (3.1% and 3.5%, respectively). Fewer women than
      men had Q-wave myocardial infarction (0.5% versus 1.6%; P = 0.02). During the
      follow-up period (mean, 4 years), no significant differences were noted between
      women and men in overall survival (81% and 85% at 6 years, respectively) or
      survival free of Q-wave myocardial infarction (81% and 83% at 6 years,
      respectively) with use of the Kaplan-Meier method. Women were less likely than
      men to have had coronary artery bypass grafting (19% versus 22% at 6 years; P =
      0.02), and the occurrence of severe angina was higher in women than in men (52%
      versus 44% at 6 years; P = 0.001). A subgroup analysis of patients who had
      myocardial infarction within 7 days preceding PTCA showed a similar pattern of
      results. CONCLUSION: After PTCA performed for unstable angina and rest pain,
      survival rates were excellent in both women and men, and no difference was
      observed in subsequent myocardial infarction rates. During follow-up, however,
      women were more likely to have severe angina and were less likely to have had
      coronary artery bypass grafting. Concerns about possible sex-related
      complications should not dissuade physicians from performing PTCA when clinically
      indicated for unstable angina and rest pain.

PMID- 9005289
TI  - The physician and the Internet.
AB  - The Internet is one of the greatest developments in informational exchange during
      the past century. It allows almost anyone to access information available
      throughout the world. Nonetheless, the Internet is often misunderstood by
      physicians. It can be considered a super computer network that allows users to
      transfer a wide variety of information at a low cost. The information can be
      transferred through functions such as electronic mail, file transfer protocols,
      the Usenet, or the most widely recognized World Wide Web. Electronic mail
      functions like the usual postal service but is carried through the Internet, and
      delivery is usually within the hour. It can serve as a method of communication
      between physicians and patients. File transfer protocols function as a method for
      transferring large amounts of information such as software through the Internet.
      The Usenet acts like an international bulletin board service, allowing users
      anywhere to post messages and to respond to messages from other users. Several
      patient support groups have Usenet sites for exchanging specific disease
      information. The World Wide Web has received the greatest attention because most
      of the information on the Internet is text, sound, or pictures. Numerous medical
      organizations have established Web sites. This article attempts to describe each
      of these functions and the benefits to physicians.

PMID- 9005288
TI  - Genetics of breast cancer.
AB  - Familial breast cancer is characterized by young age at diagnosis, an increased
      risk of bilateral breast cancer, an increasing risk in conjunction with
      increasing numbers of affected family members, and a strong association with
      ovarian cancer. At least eight candidate breast cancer susceptibility genes have
      been identified. Mutations in BRCA1, BRCA2, p53, and the Cowden disease gene are
      relatively uncommon, are highly penetrant, and produce striking familial clusters
      of breast cancer. BRCA1 and BRCA2 are the most important of these, accounting for
      an estimated 80% of hereditary breast cancer and 5 to 6% of all breast cancers.
      Specific BRCA1 and BRCA2 mutations are of particular importance in population
      subgroups, such as those identified among Jewish women of central European
      (Ashkenazi) origin. Mutations in the ataxia-telangiectasia gene and the rare
      HRAS1 variable number of tandem repeats polymorphisms are much more common but
      also much less penetrant. They do not produce dramatic familial aggregations of
      breast cancer but may prove to be responsible for a substantial proportion of all
      breast cancers if their epidemiologic association with breast cancer is
      confirmed. Predictive genetic testing for breast cancer risk is under way.
      Oncologists and primary-care physicians must become familiar with these genetic
      disorders and the issues surrounding predictive testing in order to make
      appropriate management decisions about women thought to have a high genetic risk
      of breast cancer.

PMID- 9005290
TI  - 64-year-old woman with chronic epigastric pain.

PMID- 9005291
TI  - Lung transplantation: where are we today?

PMID- 9005292
TI  - Surgical issues in lung transplantation: options, donor selection, graft
      preservation, and airway healing.
AB  - To present an overview of the surgical issues in lung transplantation, including
      the historical context and the rationale for choosing a particular procedure for
      a specific patient, we reviewed and summarized the current medical literature and
      our personal experience. Several surgical options are available, including single
      lung transplantation; double lung transplantation; heart-lung transplantation;
      bilateral, sequential single lung transplantation; and (recently) single lobe
      transplantation. Although single lung transplantation is preferred for maximal
      use of the available organs, bilateral lung transplantation is necessary for
      septic lung diseases and may be appropriate for pulmonary hypertension and
      bullous emphysema. Heart-lung transplantation is performed for Eisenmenger's
      syndrome and for primary pulmonary hypertension with severe right ventricular
      failure. General factors for consideration in assessment of compatibility of the
      donor and potential recipient include ABO blood group, height (the donor should
      be within +/- 20% of the recipient's height), and length of the lungs (determined
      on an anteroposterior chest roentgenogram). Graft preservation and minimal
      duration of ischemia are important. Complications associated with airway healing
      are related to ischemia of the donor bronchus. We have addressed the issue of
      donor bronchial ischemia by direct revascularization of the donor bronchial
      arteries with use of the recipient's internal thoracic artery. Currently, lung
      transplantation offers a realistic therapeutic option to patients with end-stage
      pulmonary parenchymal or vascular disease.

PMID- 9005293
TI  - Lung transplantation: selection of patients and analysis of outcome.
AB  - Lung transplantation is an important option for patients with respiratory failure
      and limited life expectancy. Herein we review the current indications for and
      outcome after lung transplantation. These results are compared with the natural
      history of various respiratory diseases, estimated from available databases.
      Candidates for lung transplantation are generally younger than 60 years of age,
      have a limited life expectancy because of end-stage lung disease, and have no
      other major organ dysfunction. Single lung transplantation is performed most
      commonly for emphysema, pulmonary fibrosis, and pulmonary hypertension. Survival
      after single lung transplantation is approximately 70% at 1 year, 60% at 2 years,
      and 40% at 3 years. The median duration of survival for patients with end-stage
      lung diseases ranges from approximately 2 to 6 years, with wide variation based
      on the diagnosis and severity of illness. Currently, prolongation of the average
      survival has not been clearly substantiated after lung transplantation. Further
      evaluation of outcomes, functional status, and quality of life after lung
      transplantation is necessary.

PMID- 9005294
TI  - Effect of gender on angioplasty outcome: are we closer to the answer?

PMID- 9005295
TI  - Treatment of non-insulin-dependent diabetes mellitus.

PMID- 9005296
TI  - Purine analogues for treatment of refractory essential mixed cryoglobulinemia.

PMID- 9005297
TI  - [Long-term inhibition of gastric acid secretion. Evaluation and healing of
      Helicobacter pylori infection?].

PMID- 9005298
TI  - [Endoscopic palliation of malignant esophageal stenoses].
AB  - The choice of the appropriate endoscopic procedure for treating a malignant
      esophageal obstruction depends on the tumor localisation, the tumor
      configuration, on specific patient data and last but not least on the technical
      possibilities of the hospital involved. Successfully performed is the mechanical
      dilatation, the tube insertion and stent implantation, the laser therapy, the
      argon plasma coagulation and the local sclerotherapy. The procedures differ in
      rate of complication, long term palliation and the improvement of dysphagia. In a
      case discussion we demonstrate that in the wide range of disease and patient
      specific facts that have to be dealt with, only the combined use of different
      endoscopic procedures will lead to the best results.

PMID- 9005299
TI  - [Distal stenosis of the choledochus in chronic pancreatitis: endoscopic drainage
      or operation?].
AB  - With the less invasive techniques for complications regarding chronic
      pancreatitis, such as tubular choledochostenosis, the endoscopic transpapillary
      bile drainage therapy by means of endoprosthesis has undergone an enlargement of
      its indications range. Blocked and dislocated prostheses, however, further raise
      the already existing possibility of septic complications. With 15 out of 43
      patients undergoing medium-term endodrainage treatment, we observed different
      resulting conditions of chronic cholestasis, such as abscess-forming cholangitis,
      hepatic abscesses, retroperitoneal phlegmon and sepsis up to biliary cirrhosis.
      Thus, in the case of chronic pancreatitis we still regard choledochostenosis-
      which, due to scarring, is mostly fixed-as a primary indication for operation.

PMID- 9005300
TI  - [Treatment of watermelon stomach (GAVE syndrome) with endoscopic argon plasma
      coagulation (APC). A new therapy approach].
AB  - The case of a 74-year-old male patient with a watermelon stomach (GAVE-syndrome:
      gastric antral vascular ectasia) is reported. The superficial annual mucosa
      showed the characteristic picture of ectatic capillaries, some of them plugged
      with fibrin thrombi. Anemia due to chronic blood loss had developed in our
      patient. The vascular lesions of the antral mucosa were treated endoscopically in
      three sessions with an argon-plasma-coagulation (APC). Three months after
      completion of therapy the vascular changes of the antral mucosa had resolved
      almost completely. In addition no further blood loss had occurred. Many treatment
      modalities of the watermelon stomach abnormality exist. Nowadays, vaporization of
      the vascular lesions with the Neodym-Yag laser has widely replaced surgical
      treatment. The argon-plasma-coagulation uses instead of laser energy conduction
      of electric energy by ionized argon gas (plasma), which produces coagulation
      necrosis of tissues. The potential advantages of the argon-plasma-coagulation lie
      in the limited deep penetration, which reduces the risk of perforation and the
      symmetric spread of the coagulation effects in the surrounding mucosa. These
      properties make the argon plasma-coagulation a promising tool for the endoscopic
      therapy of mucosal lesions of the GI-tract. Further attractive is the low cost of
      the argon-plasma-coagulation equipment compared with laser devices.

PMID- 9005301
TI  - [Complications of percutaneous endoscopic gastrostomy (PEG)].
AB  - Percutaneous endoscopic gastrostomy (PEG) is a simple technique for the
      endoscopic placement of a permanent feeding access. The procedure is relatively
      safe and the technique well established. PEG can, however, be associated with
      serious complications and death. Following the rare PEG-related complication of
      an abdominal dislocation we review technique, indications and complications of
      this sixteen year old method.

PMID- 9005302
TI  - [Good results with Helicobacter pylori eradication for treatment of non-ulcer
      dyspepsia].

PMID- 9005303
TI  - Proceedings of symposium on computerized behavioral testing of humans in
      neurotoxicology research. Portland, Oregon, June 21-23, 1995.

PMID- 9005305
TI  - Infant metabolic alkalosis and soy-based formula--United States. 1979.

PMID- 9005304
TI  - Prevention of hepatitis A through active or passive immunization: Recommendations
      of the Advisory Committee on Immunization Practices (ACIP)
AB  - This report provides recommendations for use of the newly licensed hepatitis A
      vaccines (HAVRIX, manufactured by SmithKline Beecham Biologicals, and VAQTA,
      manufactured by Merck & Company, Inc.) in persons > or = 2 years of age and
      updates previous recommendations for use of immune globulin (IG) for protection
      against hepatitis A (superseding MMWR 1990;39[No. RR-2]:1-5). For preexposure
      protection, hepatitis A vaccine can now be used instead of IG in many
      circumstances; for postexposure prophylaxis, the recommendations for IG use are
      unchanged.

PMID- 9005307
TI  - Iron overload disorders among Hispanics--San Diego, California, 1995.
AB  - Approximately 1.5 million persons in the United States are affected by iron
      overload diseases, which are primarily caused by hereditary hemochromatosis--the
      most common genetic disorder in the United States. Hereditary hemochromatosis is
      characterized by increased iron absorption in the gastrointestinal tract, which
      may cause lifelong excessive iron absorption and accumulation and serious health
      effects, including arthritis, cirrhosis, diabetes, impotence, heart failure, and
      death. Hereditary hemochromatosis is an autosomal recessive disease; the
      estimated prevalence of the homozygous genotype is 1:200 - 1:250 persons, and 10%
      of persons are carriers. Although the disease was previously believed to affect
      primarily white males of northern European descent, recent data indicate
      hereditary hemochromatosis also occurs among blacks. Moreover, iron overload
      diseases are underdiagnosed among whites and may not be considered in other
      racial/ethnic groups (e.g., Hispanics) even when compatible symptoms and clinical
      findings are present. As part of a joint demonstration project during August
      October 1995 to determine the overall prevalence of iron overload, CDC reviewed
      data from a health-maintenance organization (HMO) in San Diego, California; the
      prevalence among Hispanics appeared similar to that for non-Hispanic whites. This
      report presents the preliminary findings of an analysis of the prevalence of iron
      overload among Hispanics and compares these findings with nationally
      representative data from the Third National Health and Nutrition Examination
      Survey (NHANES III). These findings indicate that the prevalence of possible iron
      overload among Hispanic clients of the HMO based on initial screening was
      consistent with the nationwide prevalence of possible iron overload based on a
      single screening test for Hispanics of Mexican descent and non-Hispanic whites.

PMID- 9005306
TI  - Imported dengue--United States, 1995.
AB  - Dengue is an acute disease caused by any of four mosquito-transmitted virus
      serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) and characterized by the sudden onset
      of fever, headache, myalgias, rash, nausea, and vomiting. The disease is endemic
      in most tropical areas of the world and can occur in U.S. residents returning
      from travel to such areas. This report summarizes information about imported
      dengue among U.S. residents during 1995 and documents a substantially increased
      incidence of dengue in the Caribbean, Central America, and Mexico.

PMID- 9005308
TI  - FDA approval of a Haemophilus b Conjugate Vaccine combined by reconstitution with
      an acellular pertussis vaccine.
AB  - On September 27, 1996, the Food and Drug Administration (FDA) licensed a
      Haemophilus b Conjugate Vaccine (ActHIB) combined by reconstitution with
      diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) (Tripedia)
      for use as the fourth dose in the childhood vaccination series. This combination
      vaccine will be sold under the trade name TriHIBit. On July 31, 1996, Tripedia
      was licensed for the initial four doses of the diphtheria, tetanus, and pertussis
      vaccination series. TriHIBit is the first vaccine to be licensed in the United
      States that combines DTaP with a Haemophilus b Conjugate Vaccine.

PMID- 9005309
TI  - Update: raccoon rabies epizootic--United States, 1996.
AB  - Since 1960, rabies has been reported more frequently in wild animals than in
      domestic animals in the United States. In 1995, wildlife rabies accounted for 92%
      of animal rabies cases reported to CDC; approximately 50% of these cases (3964 of
      7881 total cases) were associated with raccoons. This report describes the
      continuing spread of an epizootic of raccoon rabies in affected mid-Atlantic and
      northeastern states and the spread into Ohio, indicating an increasing move
      westward despite geographic barriers.

PMID- 9005310
TI  - Children with elevated blood lead levels attributed to home renovation and
      remodeling activities--New York, 1993-1994.
AB  - Renovation and remodeling activities that disturb lead-based paint can create
      substantial amounts of lead dust in the home; such dust can then be inhaled or
      ingested by children. In January 1995, the New York State Department of Health
      (NYSDOH) assessed lead exposure among children resulting from home renovation and
      remodeling during 1993-1994. This report summarizes findings of the study, which
      identified 320 children in New York state (excluding New York City) with blood
      lead levels (BLLs) > or = 20 micrograms/dL that were considered to be
      attributable to residential renovation and remodeling.

PMID- 9005311
TI  - Abortion surveillance: preliminary data--United States, 1994.
AB  - For 1994, CDC received data on legal induced abortions from the 50 states, New
      York City, and the District of Columbia. This report presents preliminary data
      for 1994. Final abortion data for 1993 and 1994 will be published during spring
      1997.

PMID- 9005312
TI  - Alternative techniques of hysterectomy.

PMID- 9005313
TI  - Alternative techniques of hysterectomy.

PMID- 9005314
TI  - Alternative techniques of hysterectomy.

PMID- 9005315
TI  - Alternative techniques of hysterectomy.

PMID- 9005316
TI  - Alternative techniques of hysterectomy.

PMID- 9005317
TI  - Terazosin, finasteride, or both in benign prostatic hyperplasia.

PMID- 9005318
TI  - Terazosin, finasteride, or both in benign prostatic hyperplasia.

PMID- 9005319
TI  - Endoscopic palliation of malignant dysphagia.

PMID- 9005320
TI  - The management of chronic heart failure.

PMID- 9005321
TI  - The management of chronic heart failure.

PMID- 9005322
TI  - Absence of human T-cell lymphotropic virus type I in cutaneous T-cell lymphoma.

PMID- 9005323
TI  - Case 25-1996: tuberculous pleuritis.

PMID- 9005324
TI  - Case 25-1996: tuberculous pleuritis.

PMID- 9005325
TI  - [Borderline disorders, schizotypal and narcissistic personality disorders in
      adolescents: a useful distinction].

PMID- 9005326
TI  - [Little benefit of medical specialist after-care for case-finding of recurrence
      following treatment of endometrial or cervix carcinoma].

PMID- 9005328
TI  - [Varicose veins: surgical removal (stripping) of the greater saphenous veins is
      preferable].

PMID- 9005327
TI  - [Mortality according to ethnicity in children in The Netherlands].

PMID- 9005329
TI  - [Cavernous cerebral angioma: indications for neurosurgical removal].

PMID- 9005330
TI  - [Right ventricular function in intensive care patients].

PMID- 9005331
TI  - [Klippel-Trenaunay-type congenital angiodysplasia syndrome; medical and
      psychological aspects].

PMID- 9005332
TI  - [More recurrencies than expected following inguinal hernia surgery].
AB  - OBJECTIVE: To make an inventory of inguinal hernia repairs performed in one year,
      and to analyse the number of and origin of recurrent hernias. DESIGN:
      Retrospective. SETTING: Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.
      METHOD: Analysis of all hernia operations performed in Amsterdam and Amstelveen
      in 1994 in male patients over 18 years of age. Request of national data, computer
      data from the hospitals, hand count of all operation reports and investigation of
      patient files. RESULTS: In 1994, 1108 patients were operated for inguinal hernia
      on one or two sides. In 216/1108 (19.5%) cases recurrent hernia was involved.
      According to national statistics this occurred in 175/1123 (15.6%). In the two
      University hospitals 25.7% of all repairs were for a recurrent hernia, in the two
      hospitals with a surgical training programme this proportion was 17.9% and in the
      five hospitals without a training programme it was 18.6%. Of the early
      recurrences (within two years) 82.5% (47/57) were reoperated in the same hospital
      as before but of the late recurrences (more than 10 years) this proportion was
      only 26.8%. Only 16.6% (36/216) of the patients with a recurrence were reoperated
      by the same surgeon who had performed the prior operation. Most popular method
      for repair was a Bassini (59%). In the training hospitals more early recurrences
      were repaired than in the non-training hospitals. CONCLUSION: The percentage of
      hernia repairs for recurrent hernia is higher than national statistics suggest
      and higher than expected. Surgeons have little insight into their performance as
      many recurrences are repaired by another surgeon and many recurrences occur after
      ten years. Better training and more use of modern techniques may improve results.

PMID- 9005334
TI  - [Good results of fasciotomy in chronic compartment syndrome of the lower leg].
AB  - OBJECTIVE: To assess the results of fasciotomy in patients with a chronic
      compartmental syndrome. DESIGN: Retrospective study. SETTING: Department of
      Surgery, Central Military Hospital, Utrecht, the Netherlands. METHOD: Closed
      fasciotomy was performed in 81 patients (151 compartments) after standardized
      measurement of the pressure of the symptomatic compartment during exercise. The
      anterior compartment was affected 149 times and the lateral compartment twice.
      The pressure reading was repeated at least 3 months after the operation. All
      operated patients 6 months postoperatively were sent a written questionnaire
      inquiring about the results of the operation. RESULTS: Postoperative
      complications included a neurinoma (3 times) and a seroma (once). The mean
      postoperative intramuscular pressures were lower than the preoperative ones: the
      pressure at rest fell from 22.1 to 14.0 mm Hg (p < 0.05), the exercise pressure
      from 57.5 to 25.4 mm Hg (p < 0.01) and the relaxation pressure from 34.4 to 25.2
      mm Hg (p < 0.05). Ten patients had an unchanged increased pressure after the
      operation, for which a second fasciotomy was performed 4 times. Attenuation of
      symptoms was reported by 59 patients (76%). Nine patients with poor results had
      already had a combination with some other hyperpressure injury before the
      operation. CONCLUSION: Closed fasciotomy in a demonstrated chronic compartmental
      syndrome in most cases gave good results, viz. attenuation of symptoms and a
      decrease of the intramuscular pressure, especially after exercise.

PMID- 9005333
TI  - [High percentage of antibiotic resistance in Shigella infections in children in
      Curacao].
AB  - OBJECTIVE: To evaluate antimicrobial treatment and resistance in clinical
      childhood shigellosis. DESIGN: Retrospective. SETTING: St. Elisabeth Hospital,
      Willemstad, Curacao, Dutch Antilles. METHOD: From September 1991 through August
      1995 shigellosis was diagnosed in 93 children out of 456 hospitalised with
      gastroenteritis (S. flexneri in 60, S. sonnei in 32, S. dysenteriae in 1). From
      hospital and laboratory records, the clinical presentation, antibiotic treatment
      and duration of hospitalization were indexed as well as the antibacterial
      resistance pattern of shigellae. RESULTS: Of the hospitalised children 52 (56%)
      were treated with antibiotics. Ampicillin was given most frequently (71%),
      followed by the combination trimethoprim-sulfamethoxazole (25%). Isolated
      shigellae were resistant to ampicillin in 52% and to trimethoprim
      sulfamethoxazole in 34%; 42% of the antibiotic treatments were in accordance with
      susceptibility of the isolated Shigella. CONCLUSION: A high percentage of
      shigellae isolated on Curacao was resistant to the most frequently used
      antibiotics ampicillin and trimethoprim-sulfamethoxazole.

PMID- 9005335
TI  - [Campylobacter infections in pregnancy].
AB  - In two pregnant women aged 39 and 35, who presented with fever and diarrhoea,
      Campylobacter was cultured from a blood sample. They were treated with
      antibiotics. One had a healthy neonate, in the other intrauterine foetal death
      had occurred. Campylobacter species have increasingly been recognized as possible
      causes of septic abortion, premature labour and neonatal sepsis. Early
      recognition and treatment of maternal Campylobacter infection may reduce the risk
      of serious foetal or neonatal complications.

PMID- 9005336
TI  - [History of healing; early reception of the anti-syphilitic agent Salvarsan in
      The Netherlands (1910-1911)].

PMID- 9005337
TI  - [Value of laparoscopic staging and palliative treatment of peri-ampullary tumors;
      the Stentby Study].

PMID- 9005338
TI  - [Drug treatment of sex disorders in men].

PMID- 9005339
TI  - [Familial combined hyperlipidemia].

PMID- 9005340
TI  - [Developments in and results of surgical treatment of pleomorphic adenoma of the
      parotid gland in 245 patients, 1974-1994].

PMID- 9005341
TI  - [Diagnosis and discharge destination of patients admitted for mental dysfunctions
      in a geriatric department].

PMID- 9005342
TI  - [Monoamine oxidase inhibitors in psychiatry. Status of current knowledge].
AB  - With the introduction of moclobemide as the first reversible and selective
      inhibitor of monoamine oxidase (type A), the therapeutic principle of monoamine
      oxidase inhibition gained new importance. In this paper the clinical
      pharmacology, efficacy and side effects of traditional monoamine oxidase
      inhibitors and specifically of tranylcypromine as an example) are compared with
      those of the reversible and selective monoamine oxidase inhibitors (as
      exemplified by moclobemide).

PMID- 9005344
TI  - [Event related brain potentials as indicators of neurochemical dysfunctions in
      psychiatric patients].
AB  - The increasing knowledge concerning anatomical structures and cellular processes
      underlying event-related potentials (ERP) and methodological advances in ERP data
      analysis are beginning to bridge the gap between ERP and neurochemical aspects.
      ERP reflect directly postsynaptic effects of cortical neurotransmitters (e.g.
      GABA, glutamate) and indirectly modulating effects of neuromodulators (e.g.
      serotonin, acetylcholine) on cortical neuronal functioning and are therefore
      promising as noninvasive indicators of the functioning of neurochemical systems.
      Several recent reports are summarised suggesting that quite specific
      relationships may exist between certain ERP parameters and central cholinergic,
      noradrenergic and especially serotonergic function. Converging arguments from
      preclinical and clinical studies are presented supporting the hypothesis that the
      dependence of the response of primary auditory cortices on stimulus intensity
      (loudness) is regulated by the level of central serotonergic neurotransmission.
      This intensity dependence is shown to be of clinical value because, within
      different diagnostic categories, subgroups of patients with a serotonergic
      dysfunction can be identified and can be treated more specifically with
      serotonergic drugs.

PMID- 9005343
TI  - [Electroencephalography in psychiatry--current status and outlook].
AB  - The "Psychophysiology Working Group" of AMDP (Arbeitskreis fur Methodik und
      Dokumentation in der Psychiatrie) intends to establish a broad database of EEG
      data in psychiatry. The purpose is to determine whether the EEG can contribute to
      the diagnostic classification of psychiatric disorders, the description of the
      course of the illness and prediction of the therapeutic outcome. Since several
      studies have shown promising results in recent years, members of the working
      group have investigated literature and written reviews that are summarized in
      this contribution. This includes a critical evaluation of the studies cited. We
      restrict ourselves to schizophrenia, affective disorder and anxiety disorder. Out
      of more than 3000 available contributions in the world literature, 500 have been
      evaluated by the group, and around 90 are taken for this summary. The critical
      review is the basis for future research of the working group and gives the
      following working hypothese. Under resting EEG conditions anxiety does not show
      typical deviations from normality. However, EEG recordings under experimentally
      induced anxiety do show typical changes: in normal persons there is usually an
      increase in desynchronous fast beta activity (hyperarousal accompanied by
      cognitive coping), whereas patients with anxiety disorder show hypersynchronized
      alpha activity, as is usually found in deep relaxation. Thus, hypersynchronized
      alpha activity might be an expression of a compensatory effort of the system to
      relax. Anxiolytics induce synchronous 14-18 Hz beta or sub-alpha activity, which
      may force the system into more rigid patterns (relaxation) and thus could
      counteract anxiety in normal persons if hyperarousal together with
      desynchronization is not sufficient. Furthermore, benzodiazepines also show an
      increase in desynchronous fast beta activity, preferably in the frontocentral
      areas, which could be useful in chronic anxiety in order to support cognitive
      efforts. While depressive disorders cause a variety of changes in the awake EEG
      that can only partly be linked with the clinical picture (neurotic versus
      endogenous), the sleep EEG shows a decrease in REM latency, and increase in REM
      density and a decrease in sleep efficiency in patients with depressive symptoms.
      However, nosological specify is not yet established. Successful antidepressive
      therapy counteracts these changes. The common feature in the awake EEG is the
      interaction with vigilance-dependent variables in both directions: stimulation
      and sedation. Schizophrenia shows different patterns for acute and chronic
      states. In acute schizophrenia there is a dysrhythmic activity with an increase
      in beta activity. This is counteracted by neuroleptics, inducing a slowing of
      frequency and an increase of synchronization. In chronic schizophrenics, there is
      increased synchronization with low variability of amplitude. In contrast to the
      treatment in acute schizophrenics, in chronic schizophrenia the therapy response
      under neuroleptics is indicated by an increase in beta activity and a decrease in
      synchronization.

PMID- 9005345
TI  - [Entactogenic drugs "ecstasy" (MDMA), "eve" (MDE) and other ring-substituted
      methamphetamine derivatives. A new class of substances among illegal designer
      drugs?].
AB  - The widely used recreational drugs 3,4-methylenedioxymethamphetamine (MDMA,
      Ecstasy) and 3,4-methylenedioxyethamphetamine (MDE, Eve) occupy an intermediate
      position between stimulants and hallucinogens. Besides stimulation similar to
      that caused by amphetamines, they usually induce a pleasant, easily controllable
      emotional state with relaxation, fearlessness and feelings of happiness, but they
      sometimes also have stronger, hallucinogenic, effects. A number of
      pharmacological studies support the hypothesis that these drugs make up a
      distinct class of psychoactive substances, which have been designated
      "entactogens." On the drug scene, MDMA and MDE are considered "safe." However,
      this view must be corrected. Complications are rare, but potentially devastating
      ([long-lasting anxiety and depressive syndromes in chronic users, fatalities with
      hyperpyrexia, rhabdomyolysis and DIC syndrome (disseminated instravascular
      coagulation), possible hepatotoxicity]. Moreover, the clinical relevance of
      animal studies showing neurotoxic effects of MDMA on central serotonergic
      pathways is still not clear.

PMID- 9005346
TI  - [Benzodiazepine withdrawal with carbamazepine].
AB  - Seventeen patients who had been dependent on benzodiazepines for more than 0.5
      years were subjected to abrupt withdrawal with carbamazepine (CBZ, 400 mg twice a
      day). Most patients were had been taking benzodiazepines because of panic
      disorder or neurosis. In 2 cases the patients were regarded as having high dose
      dependency. In 2 others withdrawal was discontinued because of loss of motivation
      or medical problems (HIV infection). During the withdrawal the patients were
      rated daily for anxiety, mood alterations, perception disturbances, neurological
      symptoms, and vegetative signs. Perception disturbances were noted in 14
      patients. Most patients showed sleep disturbances, mood alterations or anxiety.
      Epileptic seizures, a well known complication of benzodiazepine withdrawal, did
      not occur. The CBZ treatment was well tolerated by all patients and caused no
      severe problems. Compared with a gradual tapering off of benzodiazepines, abrupt
      withdrawal plus CBZ medication seems to be better tolerated; in particular, the
      period of hospitalization for these patients can be shorter. Because anxiety, the
      reason for the benzodiazepine treatment in many cases, often recurs, the patients
      must be offered continuous after-care to prevent a new dependence.

PMID- 9005348
TI  - [High dosage tranylcypromine treatment of "therapy refractory" depressions].
AB  - Refractory depression is a significant problem in hospital medicine especially
      under in-patient treatment conditions. On the basis of a case report, the
      importance of treatment with high-dose tranylcypromine as a useful therapeutic
      strategy in refractory depression is discussed.

PMID- 9005347
TI  - [Successful carbamazepine therapy of 2 cases of music hallucinations].
AB  - We report on two elderly female patients who experienced musical hallucinations.
      Both were suffering from deafness in addition to non-specific organic brain
      changes. In both patients the musical hallucinations were successfully treated
      with carbamazepine.

PMID- 9005349
TI  - [Phase prevention in bipolar affective disorder with nimodipine. A case report].
AB  - A 56-year-old female patient had a history of more than 10 years' duration of a
      bipolar affective disorder manifest mainly as depressive episodes. These episodes
      used to occur once or twice each year, frequently leading to hospital admission.
      On average, the episodes lasted for about 2 months, and they tended to be
      followed by brief periods of hypomania. Only once, in 1986, did a manic episode
      make hospitalization necessary. Attempted prophylaxis with lithium at therapeutic
      plasma levels did not prove effective. Treatment with carbamazepine was
      discontinued because of leukopenia. The most recent stay in hospital became
      necessary because of a depressive episode that lasted for 5 months and did not
      respond to therapy. On admission the patient's score on the Hamilton depression
      scale was 23. When the calcium antagonist nimodipine was given at a dosage
      quickly escalated to 360 mg daily, the patient could be discharged in a state of
      complete remission after 26 days. For the first time in many years she has been
      emotionally stable for almost 1 year with single agent nimodipine therapy at 180
      mg daily.

PMID- 9005350
TI  - [Electroconvulsive therapy in compulsive syndromes. A case report].
AB  - We report on a case of successful ECT in serious drug-resistant and psychotherapy
      resistant obsessive-compulsive disorder. The 44-year old male patient had already
      had symptoms of this disorder for 4 years, and they completely disappeared after
      seven ECTs (1 bi-, 6 unilateral). After remission of the obsessions the patient
      underwent a behaviour therapy to consolidate the success of the ECT treatment and
      to prepare the patient for returning to work. He remains free of obsessions 18
      months later.

PMID- 9005351
TI  - [Successful electroconvulsive therapy of Cotard syndrome with bitemporal
      hypoperfusion].
AB  - A case study is presented to illustrate a rare condition described by Cotard as
      "delire de negation". The central symptom is a nihilistic delusion with denial of
      one's own existence of oneself and that of the external world. In the present
      case, the syndrome became manifest as an escalation of a recurrent depressive
      disorder late in life. After initial resistance to therapy, the syndrome was
      successfully treated with electroconvulsive therapy. For the first time, we
      report the regional cerebral blood flow measured by 99mTc-HMPAO-SPECT before and
      after therapy. Before treatment, significant bitemporal hypoperfusion relative to
      the cerebellum was found, which was no longer demonstrable on remission.

PMID- 9005352
TI  - [Psychopathological phenomena in long-term follow-up of acute psychosis after
      preventive mefloquinine (Lariam) administration].
AB  - There are some reports about neuropsychiatric side effects associated with the
      intake of the antimalarial drug mefloquine. We report a long-term observation of
      a patient suffering for his first time on an acute psychosis under mefloquine
      prophylaxis. Mefloquine's role as a drug possibly inducing psychosis and the
      influence of vulnerability therefore will be discussed.

PMID- 9005353
TI  - [Depressive stupor--malignant neuroleptic syndrome--serotonin syndrome. A case
      contribution to a difficult differential diagnosis].
AB  - Depressive stupor and malignant neuroleptic syndrome are very well-known problems
      in clinical psychiatry. The serotonin syndrome, however, a potentially life
      threatening side effect of treatment with serotonergic substances, has been
      included in the clinical differential diagnosis increasingly often in the last
      few years. The development of new serotonin selective antidepressants and
      selective reversible inhibitors of monoamine oxidase A has led to the use of more
      and more substances that can cause these life-threatening complications if they
      are taken in too high doses or together with other drugs. We present a 61 year
      old depressed female impatient who developed an abortive malignant neuroleptic
      syndrome while being treated for depressive stupor. We discuss a possible
      relation between serotonin syndrome and a highly dosed combination therapy with
      moclobemide. Owing to the importance of both syndromes, we consider drug
      monitoring absolutely necessary for patients who are being treated with new
      antidepressants, and especially for those who develop neurological and
      psychiatric complications when such preparations are given in combination with
      other drugs.

PMID- 9005354
TI  - [Catatonia, malignant neuroleptic syndrome and myositis ossificans].
AB  - Lethal catatonia and the malignant neuroleptic syndrome represent two potentially
      fatal disorders that require different therapeutic regimens. Clinical
      differentiation is considered difficult because of a number of similarities with
      respect to mode of onset, signs and symptoms, and outcome. Recent observations
      emphasizing similarities between the two disorders, however, suggest that
      catatonia and the malignant neuroleptic syndrome may not represent separate
      diagnostic entities. Instead, the malignant neuroleptic syndrome has been
      hypothesized to be a neuroleptic-aggravated form of catatonia. In the present
      paper, we report the case of a 22-year-old male who developed different forms of
      malignant neuroleptic syndromes subsequent to a catatonic episode and overlapping
      it. In addition, the course was complicated by the occurrence of heterotopic
      calcification within skeletal muscles. The clinical value of diagnostic criteria
      that help distinguish catatonia from neuroleptic malignant syndrome and their
      therapeutic consequences are discussed.

PMID- 9005355
TI  - [A case of malignant neuroleptic syndrome. Case report].
AB  - We report on a woman patient with organophosphate poisoning resulting from a
      psychotically motivated suicide attempt. After detoxification and during
      treatment with haloperidol and levomepromazine, she developed acute malignant
      neuroleptic syndrome (MNS) in which dyspnea requiring assisted ventilation was
      the main symptom. Discontinuation of the neuroleptics was enough to effect
      sufficient recovery. With this case report, we would first like to emphasize that
      MNS can evolve within a very short time into a severe and life-threatening
      situation requiring intensive medical care, and secondly to illustrate the
      implications of organophosphate poisoning and the consequent cholinesterase
      blocking far the differential diagnosis of MNS.

PMID- 9005356
TI  - ["Informed consent" by the patient for publication of case reports. New
      guidelines by the "International Committee of Medical Journal Editors" (Vancouver
      Group)].
AB  - The "International Committee of Medical Journal Editors" has revised its
      guidelines regarding the protection of patients' rights to privacy in manuscripts
      submitted to biomedical journals. Information that might identify patients should
      not be published unless it is essential for scientific purposes and the patient
      has given written informed consent for publication after having been shown the
      manuscript to be published. This article discusses the new guidelines in the
      clinical context of psychiatry and psychotherapy. The ethical and legal problems
      raised concern (1) the informed consent process, (2) the content of scientific
      work and (3) the problem of third party consent (e.g. legal guardians).

PMID- 9005357
TI  - [Comments on the contribution by W. Gaebel. Quality assurance in psychiatry.
      Concept-methodology-implementation].

PMID- 9005358
TI  - [Comments on the contribution by T. Steinert and P.-O. Schmidt-Michel. Borderline
      disorder and schizophrenia].

PMID- 9005359
TI  - Sherlock Holmes: neurologist?

PMID- 9005360
TI  - [Pregnancy in women over 35 years of age. What risk?].
AB  - A retrospective study of women who are delivered at the Dept. of Obstetrics and
      Gynecology at the University of Bari, in the period 1991-1994, was performed to
      evaluate if over 20 week pregnancies in women aged 35 years and over were at
      higher risk for maternal and neonatal complications than pregnancy in women aged
      20 to 29 years. The results of these 4 years show that pregnancy in women aged 35
      and over is burdened with a greater incidence of maternal complications and
      cesarean sections, but age is not a risk for neonatal outcomes. Moreover, most
      working women were obliged to delay the first birth child, but work does not
      increase the number of complications.

PMID- 9005361
TI  - [Folic acid and cervix dysplasia].
AB  - The localized folate deficiency, which is sometimes misdiagnosed as cervical
      dysplasia, because of morphological similarities between the cytologic features
      of megaloblastosis seen with folate deficiency and the changes associated with
      dysplasia, could be a component of the dysplastic process. In this study we
      attempted the effect of oral folic in women with cervical dysplasia. A total of
      154 subjects with grade 1 or 2 CIN were randomly assigned either 10 mg of folic
      acid or a placebo daily for 6 months. Clinical status, human papillomavirus type
      16 infection and blood folate levels were monitored at 2 month intervals. After 6
      months no significant differences were observed between supplemented and
      unsupplemented subjects regarding dysplasia status, biopsy results, or prevalence
      of human papillomavirus type 16 infection. Folate deficiency the initiation of
      cervical dysplasia, but folic acid supplements do not alter the course of
      established disease.

PMID- 9005362
TI  - [Hysteroscopic features in postmenopausal uterine bleeding].
AB  - One hundred forty three patients underwent hysteroscopy for abnormal uterine
      bleeding from January 1993 through December 1994. Sixty patients were
      postmenopausal. All but 3 of the procedures were performed on outpatient with no
      significant complications. Three groups could be identified on the basis of
      endometrial features (color, vascularity, thickness, necrotic areas): 1) negative
      for cancer, 2) possible or suspect (low or high risk), 3) carcinoma. Biopsy
      indicated cancer in one of the 16 doubtful cases, and in all (5) of the
      hysteroscopically diagnosed cancers. Outpatient Hysteroscopy successfully
      substitutes D&C (dilatation and curettage) for early diagnosis of endometrial
      cancer.

PMID- 9005363
TI  - [Course and regression of HELLP syndrome].
AB  - The authors reported the outcome of a retrospective study of patients with HELLP
      syndrome to verify whether this pathology is a clinical entity with models of
      evolution, regression and well defined treatment. A total of 20 individual cases
      were reported at the Division of Obstetrics and Gynecology at the G. Gaslini
      Institute during the period from January 1990 to September 1995. All cases showed
      the normalisation of the various clinical and hematochemical parameters within a
      maximum of 8 days after birth. The rapid diagnosis, the immediate extraction of
      the fetus and appropriate medical treatment led to the prompt resolution of this
      severe pathology without the need for demolitive surgery frequently used in the
      past.

PMID- 9005364
TI  - [Prevalence of RDS in diabetic pregnancy].
AB  - The offspring of the diabetic mother is more significantly affected by RDS
      (Respiratory Distress Syndrome) than the healthy pregnancy's one in the same
      conditions. The RDS is one of the most important cause of perinatal morbidity and
      mortality. The etiology of this syndrome is recognized in the modified
      carbohydrates metabolism, in the apposite effect of insulin versus the cortisol
      action, and in the slower adsorption of the alveolar fluid following the Cesarean
      section. In fact the diabetic mother is frequently submitted to this intervention
      to end the pregnancy and especially in last years when the CS was of first choice
      at 35 weeks in the diabetic mothers. Actually the RDS appears in the 13% of the
      offspring of mothers affected by pregestational diabetes and in the 5% of the
      offspring of gestational diabetic mothers. Here we refer about the prevalence of
      RDS in a population of 55 diabetic mothers.

PMID- 9005365
TI  - [Brain metastases in patients with malignant ovarian epithelial tumors].
AB  - From September 1983 to September 1994, 23 patients with Central Nervous System
      (CNS) metastases from ovarian carcinoma were observed in our institution. The
      mean age at the time of CNS metastases diagnosis was 59 years, the mean interval
      between diagnosis of ovarian carcinoma and documentation of the CNS involvement
      was 35 months. All the patients presented neurological symptoms. One patient had
      meningeal carcinomatosis; 22 presented parenchymal lesions. Nine patients had a
      single CNS lesion and 13 had multiple metastatic sites. CNS was the only site of
      disease in 9 patients, while 8 had concomitant extraperitoneal dissemination.
      Four patients received hormonal treatment with a mean survival (MS) of 3 months;
      14 received radiotherapy alone (MS 5.5 months), 5 underwent surgical resection of
      solitary lesion followed by radiotherapy (MS 17 months). Number of CNS lesions,
      extent of the disease at time of CNS metastases and the treatment were the
      factors which significantly affected survival. The prognosis of these patients
      appears poor, however, early diagnosis followed by multimodal treatment may
      result in significant palliation an improve overall survival in a selected group
      of patients.

PMID- 9005366
TI  - [Incidence of climacteric syndrome].
AB  - A retrospective study on 300 women who attended the menopausal out-patient clinic
      of Physiopathology of Human Reproduction at Bari University Hospital from 1994 to
      1995, was carried out to evaluate the incidence of climacteric syndrome in
      premenopause together with its correlations with the social and cultural
      environment. The results don't show differences between spontaneous and surgical
      menopause, and minor differences with premenopause. No relationship has been
      discovered between the onset of the menarche and the onset of spontaneous
      menopause. The hot flushes are more frequent in women with low level of learning.

PMID- 9005367
TI  - [Principles of the clinical evaluation of the vulvar region].
AB  - The clinical examination of the vulva, using an articulated method, should form
      part of the routine gynecological examination thus enabling both the correct
      diagnosis and treatment of numerous alterations and the prevention and early
      diagnosis of VIN and invasive neoplasias. A correct evaluation should include
      basic anamnestic data, a list of symptoms localised in the vulva region, a
      careful inspection and palpation. The successive aim is to identify the main
      clinical aspects of the lesion which can be summarized as changes of colour,
      presence of swellings on surface and loss of substance. The critical evaluation
      of lesions should allow critical evaluation of lesions should allow the
      gynecologist to formulate a diagnosis to propose to the pathologist. In this way
      the collaboration between clinician and pathologist can contribute to progress in
      the diagnosis and treatment of vulvar diseases.

PMID- 9005368
TI  - [Effects of ipriflavone on bone loss induced by GnRH analog].
AB  - The aim of this study is to evaluate the association between GnRH analogues and
      ipriflavone, drug modulating the bone turnover limiting the negative bone effects
      of analogue. Thirty patients (33 +/- 5.4 years, mean +/- SD) affect by benign
      gynecological conditions in which there was an indication to use GnRH analogs
      have been treated with leuprolide acetate at the monthly intramuscular dose of
      3.75 mg, for six months. Fifteen of these patients also received 600 mg/day per
      os of ipriflavone (group A), while the other 15 patients have been treated
      exclusively with leuprolide acetate (group B). Before and after treatment, radial
      bone mineral density (BMD) and main markers of bone turnover were measured in all
      patients. Before treatment no difference in the considered parameters could be
      detected between the two groups. In group A, after 6 months of treatment no
      significant decrease in BMD and no variations in the bone turnover parameters. On
      the contrary, in group B, after six months of treatment, a significant decrease
      (p < 0.05) in BMD was observed in comparison to basal and group A values. In the
      same group alkaline phosphatase, osteocalcin and urinary calcium/creatinine and
      hydroxyproline/creatinine ratio proved significantly increased in comparison to
      basal and group A values (both with p < 0.05). Ipriflavone, therefore, seems to
      be effective in counteracting the negative effects of GnRH-a induced on bone.

PMID- 9005369
TI  - [Drug treatment in vulvar lichen sclerosus].
AB  - This study was made in the Oncologic Gynecology's surgery of the Department of
      Obstetrics and Gynecology of the University of Naples. We evaluated the efficacy
      of local therapy with testosterone and progesterone in Vulvar Lichen Sclerosus.
      We treated 65 women suffering from Vulvar Lichen Sclerosus. In the group of 38
      women treated with testosterone, we observed a complete response in 26 cases
      (68%). In the group of 27 women treated with progesterone we observed a complete
      response in 18 cases (66.6%). This demonstrates the efficacy of local therapy
      with testosterone and Progesterone in Vulvar Lichen Sclerosus. The authors
      believe that medical treatment with topical testosterone and progesterone
      represents an effective alternative to invasive methods for the care of Vulvar
      Lichen Sclerosus.

PMID- 9005370
TI  - [Use of a new ultrasonographic contrast medium (Echovist-200) in the study of the
      tubal factor of infertility].
AB  - OBJECTIVE. Use of a new sonographic contrast medium (Echoivist-200) for the
      evaluation of tubal patency and morphology. DESIGN: Comparative study. SETTING:
      Istituto di Ginecologia ed Ostetricia dell'Universita di Genova. PATIENTS: Thirty
      women with primitive or secondary infertility since al least two years.
      INTERVENTIONS: Hysterosonosalpingography has been performed on patients using a
      new sonographic contrast medium. MEASUREMENTS: Tubal patency and morphology have
      been evaluated. RESULTS: This procedure allowed to obtain a correct diagnosis in
      86% of cases. 83% of patients had light pelvic pain, 20% of them experienced
      nausea and vomiting in one case a lipothymia occurred. CONCLUSIONS:
      Hysterosonosalpingography with a new sonographic contrast medium should become
      the first choice procedure in the evaluation of tubal patency, addressing to the
      radiological examination only the uncertain cases or cases in which, the presence
      of a proximal tubal obstruction could be treated by selective catheterization.

PMID- 9005371
TI  - [Screening for carcinoma of the cervix today].
AB  - A revision of the more recent literature has been made in the order to establish
      which are, actually, the "gold standard" procedures in the planning out and the
      management of screening programs for cervical cancer. The problem of the false
      negatives responses, which make necessary the adoption of adequate reporting
      systems and quality control programs, is relevant. A centralized and "organized"
      screening policy, involving most of the female population, is also mandatory,
      keeping in the mind the amount of work for the public health services. The
      ultimate goal is to assure a "cover" percentage higher than the actual levels,
      reaching an acceptable balance in terms of cost-efficiency.

PMID- 9005372
TI  - [Transvaginal color-Doppler sonography for monitoring the response to neoadjuvant
      chemotherapy in patients with locally advanced cervical cancer].
AB  - Changes in blood flow characteristics, observed with transvaginal color-Doppler
      ultrasonography have recently been reported in patients with advanced cervical
      cancer. In order to evaluate the reliability of TVCDUS in monitoring the response
      to neoadjuvant chemotherapy in patients with locally advanced cervical cancer, a
      prospective study was undertaken on the blood flow characteristics of the
      cervical vessels. Pulsatility Index (PI) and Resistance Index (RI) of the uterine
      and cervical arteries of 12 patients with histologically proven advanced cervical
      cancer, scheduled for neoadjuvant chemotherapy were evaluated at diagnosis,
      during every cycle of chemotherapy and before surgery. A significantly lower
      value of mean PI and RI between cervical and uterine arteries was observed in
      patients with cervical cancer (PI = 1.671 +/- 0.18 vs 2.159 +/- 0.24)-(RI = 0.43
      +/- 0.17 vs 0.72 +/- 0.22). Mean RI and mean PI of the descending branches of the
      uterine arteries were significantly lower in patients with cervical cancer,
      compared to healthy control women. No difference in blood flow parameters could
      be detected between stage I vs stage II-III, and between left and right cervical
      artery in patients with cervical cancer. Both RI and PI values appeared strictly
      related to the tumor response to chemotherapy. In fact in 8 patients in which
      treatment resulted in tumor regression, evaluated by pelvic examination and MR
      imaging, a significant (p < 0.01) increase of resistance indices was observed (PI
      = 1.671 +/- 0.18 vs 2.158 +/- 0.22)-(RI = 0.43 +/- 0.17 vs 0.79 +/- 0.16). On the
      other side 4 patients not responding to chemotherapy, had stable values of both
      PI and RI. Transvaginal color-Doppler ultrasonography might be useful in
      monitoring the response to neoadjuvant chemotherapy in patients with locally
      advanced cervical carcinoma.

PMID- 9005373
TI  - [Visualization of the fetus in early pregnancy with transvaginal sonography].
AB  - The aim of this prospective study is to define in early pregnancy the time and
      percentage of visualization of embryo-fetal structures and organs. 820 patients
      at high risk for fetal genetic anomalies and/or malformations were scanned by
      high resolution transvaginal probe between 10 and 16 weeks' gestational age.
      Criteria for exclusion were: fetal malformations, multiple pregnancies and loss
      of pregnancy. We determined percentage of visualization in the different weeks
      of: orbits, face, cerebellum, cisterna magna, cardiac chambers, abdomen,
      diaphragm, stomach, kidneys and bladder. The percentage of visualization of fetal
      organs and structures investigated increased with gestational age and at 13 weeks
      ranged from 80% to 100%. With the introduction of high-frequency transvaginal
      probes in early pregnancy embryo-fetal structures and organs can be imaged and
      studied in great detail and more accurately identified than with traditional
      abdominal ultrasound, up to 4 weeks earlier. Another important advantage is the
      fact that some fetal malformations can be detected earlier.

PMID- 9005374
TI  - [Condition at birth of a group of neonates suffering from intrauterine growth
      retardation].
AB  - The authors monitored a group of pregnant patients who presented fetuses with
      intrauterine retarded growth syndrome. Only pregnant women who were monitored
      until the time of birth were included in the study. Patients were divided into
      three groups depending on the week of gestation in which birth occurred and two
      subgroups were identified within each group depending on the type of birth. Three
      perinatal deaths (5%) were recorded in the group of patients at risk, a
      percentage that is comparable to data reported in the literature, in spite of
      careful monitoring (flow metric and cardiographic). Cesarian section was resorted
      to in 86.4% of cases and 67.7% of neonates presented decisively "poor" conditions
      at birth.

PMID- 9005375
TI  - [Screening for bacterial vaginosis in a population of pregnant women reporting to
      cardiotocographic tests].
AB  - Of 753 patients repeatedly controlled by nonstress test the incidence of
      bacterial vaginosis amounted to 11.28%. As regards the bacterial kinds isolated
      we have not noticed expressive differences in relation to the different periods
      of pregnancy, with the exception of the Candida albicans that instead has been
      the more frequent and in constant increase. Before the 30th week of pregnancy
      until the 35th, more variety of bacterial flora, with prevalence of aspecific
      vaginitis has been observed. The incidence of premature birth has been 5.86% for
      positive cases only and 0.66% for all cases controlled by nonstress test. In the
      five cases observed the bacterial kinds Gardnerella vaginalis, Ureaplasma
      urealitycum and Streptococci beta hemol of B group in association with Candida a.
      have been isolated.

PMID- 9005376
TI  - [Breast feeding. The importance of correct management].
AB  - The advantages that breast-feeding still offers over bottle-feeding are widely
      recognized. This study has the following aims: 1) to verify how many of the women
      that delivered during the last biennium at the Midwifery School of Camerino
      breastfed their infants for a fair amount of time; 2) to evaluate the
      relationship between the results obtained and the protocols followed in the
      management of the various issues connected with breast-feeding. The research was
      carried out into a sample of 140 women, randomly selected. The anamnestic and
      clinical data obtained from the medical cards were integrated with information
      gathered by telephonic interviews. Less than 40% of the women of the sample gave
      their infants only maternal milk for a very good period. The inobservance of many
      WHO guidelines for the promotion of breast-feeding seems to be the main cause of
      the disappointing results obtained. Some groups of women proved more exposed to
      the risk of inadequate suckling: teenagers, the older gravidae, women that
      delivered prematurely, those that had children with a low birth weight, the women
      that had previous breast-feeding failures, smokers, women that attended a course
      of psychoprophylaxis, women with the lowest socioeconomic standards, mothers that
      were precociously separated from their babies, women that had some gestational
      pathology or some problems during the first days after delivery, women that had
      as main reference doctors without a proper breast-feeding culture.

PMID- 9005377
TI  - [The role of hysteroscopy in the early diagnosis of small, focal endometrial
      neoplasms].
AB  - Hysteroscopy is a useful methodology for the diagnosis of uterine intracavitary
      disorders in women suffering from abnormal uterine bleeding. The authors report a
      case of small endometrial adenocarcinoma and then they discuss on validity of
      hysteroscopy in comparison with blind curettage of uterine cavity for the
      precocious diagnosis of such lesion.

PMID- 9005378
TI  - [Acute abdomen in the third trimester].
AB  - The authors report a case of acute abdomen in the third trimester of pregnancy as
      observed at the II Obstetrics and Gynecologic Department of Florence University.
      Emphasis is laid on the frequent abnormality of the symptomatology and therefore
      the difficult of early diagnosis. The conclusion is reached that a greater
      semeiologic accuracy on behalf of the specialist as well as memorization of the
      several clinical charts responsible for such pathology, allow an earlier
      diagnosis with consequent improvement of maternal and fetal prognosis.

PMID- 9005379
TI  - [Torsion of uterine fibroma associated with incarcerated inguinal hernia in
      pregnancy. Case report].
AB  - The incidence of inguinal hernias in pregnancy is 1:1000 about. Much more
      frequent are uterine leiomyomas, reported in 0.5-2.6% cases. We describe a rare
      case of a 31 old woman at the 20th week of pregnancy affected with a torsion of
      uterine leiomyoma associated with right inguinal incarcerated hernia, operated
      urgently (myomectomy and Bassini inguinal plastic).

PMID- 9005380
TI  - [Intestinal intussusception in pregnancy with obstruction, caused by benign
      neurilemmoma. Role of abdominal echocardiography in the preoperative diagnosis].
AB  - A rare case of intestinalm obstruction caused by intussusception of the small
      bowel due to an intraparietal benign neurilemmoma (synonym: benign schwannoma) in
      a patient 35th weeks pregnant is reported. It is assumed that intestinal
      intussusception during pregnancy is a rare complication and the diagnosis is made
      difficult due to the pregnancy itself, delaying the onset of symptoms and
      treatment. The echography was the determining factor for the diagnosis. The
      conclusion is drawn that surgical operation, associated or not with the cesarean
      section, should be carried out as quickly as possible in order to reduce the
      mortality rate both maternal and fetal.

PMID- 9005382
TI  - Hepatitis B: recommendations for children/adolescents.

PMID- 9005381
TI  - [Effectiveness and tolerability of oral liquid ferrous gluconate in iron
      deficiency anemia in pregnancy and in the immediate post-partum period:
      comparison with other liquid or solid formulations containing bivalent or
      trivalent iron].
AB  - From the early months of pregnancy and even more so later, women suffer a
      deficiency of iron along with a decline in their red blood cell count. It is also
      now clear that women who take iron supplements during pregnancy do not suffer the
      same post-natal reduction in hemoglobin and ferritin as those who don't make it.
      A study was therefore conducted on 40 women aged 20-35, with iron-deficiency
      anaemia during or immediately after pregnancy all of whom presented Hb < 10
      gr/dl, Ht < 33% and serum iron < 60 micrograms/dl. All women with pregnancy
      related pathological conditions, pre-existing on concomitant disease (Type I
      diabetes, heart diseases etc.) were excluded from the study. The women whose
      blood chemical parameters were largely homogeneous at the start of the study were
      divided into four treatment groups of 10 patients each and were treated as
      follows: Group A with oral liquid ferrous gluconate (75 mg per diem in 2 vials a
      day); Group B with solid ferrous gluconate (80 mg per diem in a single
      effervescent tablet); Group C with solid ferrous sulphate (105 mg per diem in a
      single tablet); and Group D with ferric protein succinylate (80 mg per diem in 2
      vials a day). All were given iron treatment for 30 days. Treatment efficacy was
      analysed by comparing basal and final parameters using the T-test for paired
      dependent samples. The tolerance of the 4 treatment protocols was assessed by the
      analysis of any side effects such as nausea, vomiting, epigastric pain,
      diarrhoea, constipation or other disorders reported by patients during treatment.
      RESULTS: Analysis of the therapeutic efficacy parameters (red blood cells,
      hemoglobin, hematocrit and serum iron) showed significant improvements but no
      statistically significant differences between the groups. However, the Group A
      patients treated with oral doses of liquid ferrous gluconate received a
      significantly lower cumulative dose of iron elements than the other groups: in
      detail 150 mg (p < 0.05) less than Groups B and D; 900 mg (< 0.001) less than
      Group C. By the end of treatment the Group A patients revealed significant
      increases versus basal values in red blood cells (p < 0.001) 1,051,000 per mm3 or
      33%, in Hb (p < 0.001) 2.83 gr/dl or 32%, in Ht (p < 0.001) 8.32% or 32%, in
      serum iron (p < 0.05) 19.5 micrograms/dl or 61%. The same group also showed an
      increase in Ferritin amounting to 7.8 micrograms/dl or 24% of the basal value. As
      to safety, only Group A patients reported no side effects and produced no drop
      outs. Gastrointestinal and other aspecific side effects caused 1 drop-out each in
      Groups B and C and 2 drop-outs in Group D. CONCLUSION: Numerous preparations
      containing bivalent or trivalent iron are available for the treatment of iron
      deficiency anaemia during or immediately after pregnancy. It has been shown that
      preparations containing ferrous salts (+2) are more easily absorbed than those
      containing ferric salts (+3) since the former can be immediately absorbed by the
      duodenal mucosa. The study reported here reveals that oral ferrous gluconate in
      liquid form is more effective and above all better tolerated than other solid or
      liquid formulations containing elementary iron.

PMID- 9005383
TI  - [Central bronchoplastic procedures in Hungary and their outcome (198-1993)].
AB  - Bronchoplastic procedures involving the main carina are declared as central
      bronchoplasties. A nation-wide collection of these interventions performed
      between 1980 and 1993 is analysed. The study is on a total of 154 operations,
      that were 16 bifurcation resections and 14 stem bronchus resections without
      parenchyma sacrifice, 61 sleeve or wedge pneumonectomies and 63 tracheal sleeve
      or wedge right upper lobectomies or carina-plasties. Surgery alone-without
      multimodality therapy-was the choice of treatment almost exclusively. About 90%
      of these interventions were performed for highly malignant, histologically
      peripheral-type, but centrally located bronchial cancers. The hospital mortality
      and morbidity were found up to 30% (an average of appr. 17%), depending on
      surgical subsets. Cause of death were surgical at 11% (leakage, anastomotic
      dehiscence and bleeding) and non surgical at 5.8% respectively. Complications at
      another 9% were related to surgery. Data of survival suggest, that nodal state is
      the strongest predictor, but the unfavourable N2 group comprises longer survivors
      as well. Certain part of this kind of interventions is to be chosen without
      alternatives (isolated tracheobronchial resections without parenchyma-resection,
      extended pneumonectomies) while extended lobectomies are alternatives of the
      extended pneumonectomies in strict conditions. A central bronchoplastic procedure
      is justified only with hope of complete resection for its high complication rate.

PMID- 9005384
TI  - [The effect of captopril therapy on the degree of microalbuminuria in diabetic
      children and adolescents with incipient nephropathy].
AB  - In the present study the effect of angiotensin converting enzyme inhibitor
      captopril was studied in normotensive diabetic children and adolescents with
      persistent microalbuminuria (repeated albumin excretion rate higher than 30 mg/24
      h). In 1993/1994, 15 microalbuminuric patients (age: 10-17 yrs, diabetes
      duration: 6.5 +/- 3.0 yrs) had been treated with captopril (0.9 mg/kg/day for a
      period of 13.1 +/- 4.4 months). In 1992/1993, 13 patients (age: 11-17 yrs,
      diabetes duration: 5.8 +/- 2.7 yrs, study period: 12.3 +/- 4.0 months) had not
      received captopril. Same restriction of the dietary protein intake was
      recommended in both groups (less than 10% of the total calorie intake). Timed 24
      h urine samples were used to determine albumin excretion by an
      immunonephelometric method. Significant increase in microalbuminuria was observed
      in patients who had not received captopril during the study period (56.2 +/- 16.0
      mg/24 h vs. 77.8 +/- 20.1 mg/24 h, p = 0.045). There was no change in
      microalbuminuria in the captopril treated group during the study period (60.6 +/-
      19.5 mg/24 h vs. 60.4 +/- 25 mg/24 h, n. s.). No change in metabolic control and
      blood pressure was observed in the two groups during the study period. These
      results support that captopril treatment may prevent or delay the progression of
      incipient nephropathy in normotensive children and adolescents in diabetes.

PMID- 9005386
TI  - [Molecular biologic study and the factor VIII gene in hemophilia A].
AB  - Results of inversion in the intron 22 region of the VIII factor gene studied by
      Southern blot are presented. Inversion was found in 20 of 46 patients. In 14
      cases (70%) distal and in 6 cases (30%) proximal type of inversion was detected.
      The significance of the positive result in genetic counseling and in
      presymptomatic diagnosis of Haemophilia A is emphasized.

PMID- 9005385
TI  - [Ovulation induction with adjuvant antiandrogen treatment in Stein-Leventhal
      syndrome].
AB  - Ovulation induction with adjuvant antiandrogen treatment was carried out in 50
      cycles of 24 hyperandrogenic anovulatory patients. Besides the clomiphene and
      gonadotrophin (pure FSH) administration on the bases of antiandrogenic effects of
      the drugs three treatment groups (dexamethasone, sprinolactone and cyproterone
      acetate) were established. In 40 cases of 50 cycles ovulation were detected and
      11 pregnancies occurred. The authors achieved the highest ovulation and pregnancy
      rate in the group treated with cyproterone acetate. The highest progesterone and
      the lowest testosterone levels were measured in the same group. According to our
      investigations adjuvant antiandrogen treatment with cyproterone acetate advisable
      in the cases of hyperandrongenic conditions.

PMID- 9005387
TI  - [Gigantomastia in pregnancy].
AB  - A 26 year old women presented with huge enlargement of breasts from 10th week of
      her first pregnancy. Both breast became very swollen and painful, more than
      tripled in size. The skin became oedematous, red, and subsequently ulceration and
      bleeding occurred. Interruption performed at the 12th week, it didn't stop the
      process. 3 months later bilateral mastectomy with free transplantation of the
      nipples and the areoles to the abdominal wall was performed. The pathologic
      diagnosis was hyperplasia of the connective tissue elements with fibroadenomas. 6
      and 8 years later she delivered healthy babies. The authors review the literature
      of gigantomastia during pregnancy with discussion of the treatment.

PMID- 9005388
TI  - [Who was Tivadar Karoly, M.D., descendent of the royal family of Wittelsbach?].

PMID- 9005389
TI  - [Important statements by Virchow in the German journal "Archive for Pathological
      Anatomy and Physiology and Clinical Medicine". (Rudolf Virchow)].

PMID- 9005390
TI  - [In memory of Miklos Frank, M.D].

PMID- 9005391
TI  - [World Wide Web--for physicians].

PMID- 9005392
TI  - [V Conference on flow cytometry in pathologic anatomy].

PMID- 9005393
TI  - [Hodgkin's disease: clonality and derivation of Reed-Sternberg cells].

PMID- 9005394
TI  - [Comparison of the different methods of grading and staging of chronic
      hepatitis].
AB  - AIM OF THE STUDY: In the recent literature it has been emerged the importance of
      grading and staging of chronic viral hepatitis. Numerous different methods of
      grading and staging have been proposed. Purpose of the present paper was to
      compare the methods proposed by Knodell et al., Scheuer, and Ishak et al.
      MATERIALS AND METHODS: Forty consecutive cases of chronic viral hepatitis
      constituted the basis of the study. Each case was graded as mild, moderate and
      severe activity and staged according to the criteria described in the three
      methods. In particular portal-periportal activity, lobular activity and fibrosis
      were evaluated. The final evaluation of the liver biopsy, together with the
      result of each single feature, were then compared. RESULTS: The three different
      methods gave grossly similar results in the overall grading of the cases.
      Analyzing the single features, differences were noted in the evaluation of the
      lobular activity. This is probably the consequence of the different qualitative
      and quantitative criteria applied. Comparison of the data obtained by evaluating
      the extension of fibrosis was quite difficult, owing to the extremely different
      scales of grading used in each single method. CONCLUSIONS: In this study three
      different methods of grading and staging of chronic viral hepatitis were
      compared. The final evaluations of the cases obtained with the different methods
      were almost superimposable. Comparing the data obtained with long term follow-up
      of the patients may better clarify which of the different methods can have a
      prognostic value.

PMID- 9005395
TI  - [Ki-67 in carcinoma of the breast: from the frozen to the paraffin sections].
AB  - We have studied 49 breast cancers in order to evaluate the Ki-67 polyclonal
      antibody in immunohistochemical assessing of the proliferating cell index on
      paraffin embedded tissue sections. Polyclonal Ki-67 immunostaining has been
      compared with monoclonal Ki-67 immunostaining on frozen sections. This study has
      been performed on two groups of breast cancers: the first using a prospective
      method including 22 consecutive cases observed in 1994; the second one, in a
      retrospective analysis of 27 consecutive cases observed in 1987-1988. Frozen
      section have been shortly fixed with formalin, methanol and acetone and
      subsequently processed with Ki-67 monoclonal antibody. The paraffin sections,
      routinely fixed in formalin and embedded in paraffin, have been pretreated in a
      microwave oven before processing with Ki-67 polyclonal antibody. The
      proliferating cell index, expressed in a semi-quantitative evaluation as
      percentage of stained nuclei, resulted differently in the mean and in the median
      values between the frozen and the paraffin groups. The difference is bigger and
      significant in the retrospective group observed in 1987-88. On the contrary, the
      results obtained from frozen and paraffin sections of the prospective group
      observed in 1994 are comparable. The prospective and the retrospective groups
      significantly differ in the fixation time. In 1994 the specimens were fixed for
      no more than 36 hours while previously the fixation time wasn't standardized and
      often exceeded 36 hours. The Ki-67 polyclonal antibody on paraffin sections is
      comparable to the Ki-67 monoclonal antibody on frozen sections on condition that
      fixation is strikingly standardized. The immunostaining with vimentin as
      antigenicity preservation control is also advisable.

PMID- 9005397
TI  - [The museums of pathologic anatomy: a very much neglected sector of scientific
      museology, worth of reconsideration].
AB  - This brief work aims at drawing attention to the problems affecting museums of
      pathological anatomy and the possibility to revise their role and give them other
      purposes than the merely educational ones for which they are established. Current
      educational methods and tools, using sophisticated and modern audio-visual and
      multimedia systems, have been so thoroughly renewed that the preservation of
      anatomic specimens for exemplification and illustration is no longer a
      fundamental requirement. Clearly enough, Pathological Anatomy Museums need to
      change in order to meet new requirements and achieve new goals. Therefore, the
      creation as well as the revamping of a Museum should be based on the use of
      multimedia and interactive systems. These should include the collection of
      pictures of rare or peculiar cases as well as the possibility to propose pre
      established educational programmes to students, while offering to scholars other
      programmes with different levels of difficulties and historical-documentary
      information. This is the approach followed by the experimental model implemented
      in our Institute which is presented in this work. Also, the Museum should be
      responsible for collecting and safeguarding rare anatomic material or specimens
      of particular interest from a historical-geographical and chronological point of
      view. The Museum should be a biologic archive from which information can be
      trapped for study and research works. For this reason, it should not be located
      only in one place, but the information and data therein contained should be made
      available, through a computer network, in the various centres and departments of
      Pathological Anatomy. Secondly, collections of dried osteologic materials should
      be properly preserved, since they are an important educational tool of great
      value for paleopathological studies. Finally, particular attention should be
      given to the oldest museums hosting collections of anatomic artworks such as wax
      impressions and casts, which, being the expression of a specific age and
      scientific attitude, are to be considered as a cultural heritage to be
      safeguarded.

PMID- 9005396
TI  - [Correlation of the histological and cytogenetic pictures in placental tissue
      from early abortion. Does immunohistochemistry have a role?].
AB  - Ninety-four cases of early abortion have been studied. Five histological groups
      of lesion have been identified by routine histological techniques on abortion
      materials, group I corresponding to partial hydatidiform mole. Cytogenetic
      analyses have revealed chromosome anomalies in near 50% of cases with a
      prevalence of triploidies followed by trisomies and monosomies. Normal
      histological findings are more often associated with normal karyotypes and group
      I with abnormal karyotypes but a specific correlation between histological
      pattern and cytogenetic anomalies is lacking. Neither some histochemical
      reactions nor the well preserved immunohistochemical reactivities of beta-hCG,
      hPL, PLAP, AFP, cytokeratin, vimentin, desmin, factor VIII, CD 68, MIB1 (growth
      fraction), EGF-R, p53 and c-erbB-2 oncoproteins have disclosed specific
      chromosome anomalies. They have only allowed a better definition of histological
      groups. A simple histological evaluation, although extended to
      immunohistochemical reaction may not substitute the cytogenetic analyses, not
      even for purposes of preselection.

PMID- 9005399
TI  - [Diffuse pulmonary ossification and diabetes mellitus. An association not
      previously described].
AB  - Diffuse pulmonary ossification is a relatively rare, well recognized condition,
      of which a number of reports exist in the literature. While the histologic
      picture of diffuse pulmonary ossification, with its nodular and dendritic forms,
      is well know, the pathogenesis is not yet fully clarified; a number of diseases
      have been claimed to be responsible for, or associated to diffuse pulmonary
      ossification, but the association with diabetes mellitus is so far undescribed.
      That's why we report this case, along with the discussion of some pathogenetic
      hypotheses and differential diagnosis.

PMID- 9005400
TI  - [Catalyzer reporter deposition: an explosion of sensitivity in
      immunohistochemistry].

PMID- 9005398
TI  - [Fournier's gangrene: description of a case].
AB  - Fournier's gangrene, named after the french dermatologist who was the first to
      described it in 1883, is a necrotizing fasciitis which affects men's external
      genitalia and more rarely women's. In most cases the clinical onset is sudden,
      characterized by fever and local tumefaction rapidly evolving into gangrene. The
      most credited aetiology is infective and one or more aerobic and/or anaerobic
      micro-organisms are supposed to be the cause. The pathogenesis involves an
      endarteritic obliterative process affecting the small vessels of the superficial
      branch of the internal pudendal artery.

PMID- 9005401
TI  - [Pathologic anatomy and molecular biology].

PMID- 9005402
TI  - [Quantitative analysis in neuropathology].

PMID- 9005403
TI  - [Malpighi the anatomopathologist. A testimony of the Taruffi Museum of Bologna].

PMID- 9005404
TI  - [Guidelines for autopsy findings and handling of tissues of subjects with
      probable or certain Creutzfeldt-Jacob disease or other prion diseases. Italian
      Society of Pathologic Anatomy and Diagnostic Cytopathology].

PMID- 9005405
TI  - [Evaluation of the sympathetic nervous system in silent ischemia with 123I
      metaiodobenzylguanidine (MIBG)].
AB  - AIM: Examination of the integrity of the sympathetic nervous system in patients
      with angiographically proven coronary artery disease and ECG documented
      asymptomatic ST-segment depression. METHOD: Stress and rest myocardial perfusion
      scintigraphy using either Thallium-201 or 99mTc-isonitrile was performed in SPECT
      technique in order to localize ischemia or scar associated perfusion defects. 15
      min and 4 h p.i. static anterior 123I-MIBG uptake was acquired. In order to
      localize norepinephrine depletion 4 h p.i. additional 123I-MIBG SPECT acquisition
      was performed. Incidence of arrhythmias was investigated by Holter ECG. Patients
      with diabetes mellitus were excluded. RESULTS: SPECT images showed in all
      patients regional 123I-MIBG depletion which corresponded with scintigraphically
      infarcted or ischemic regions. Well perfused myocardial regions matched with
      regular 123I-MIBG uptake. There was no evidence of increased arrhythmias in long
      term ECG. CONCLUSION: The finding of regular 123I-MIBG uptake in well-perfused
      myocardium and infarction- or ischemia-associated regional 123I-MIBG depletion
      confirms that silent ischemia is not caused by a global sympathetic nervous
      dysfunction in a sense of cardiac polyneuropathy.

PMID- 9005406
TI  - [Prerequisites for diagnostic use of antisense oligonucleotides in nuclear
      medicine].
AB  - A new promising perspective in nuclear medicine is the use of radiolabeled
      antisense oligonucleotides as diagnostic markers. Especially for cancer
      diagnostics, a quantitative accumulation of antisense probes which are directed
      against abundantly expressed oncogene mRNAs seems to be reasonable. However, the
      development of this strategy still requires an optimization of several
      parameters: (i) rapid and efficient radiolabeling methods, (ii) a fast
      penetration of the probe into the target tissue, (iii) a fast internalization
      into the tumor cell, (iv) an oligonucleotide/mRNA hybrid formation with high
      specificity, and (v) a high stability of the hybrid against intracellular
      nucleases.

PMID- 9005407
TI  - [Determinations of MAG3 clearance according to the whole-body principle and to
      related methods].
AB  - To answer the question for the most effective use of all usually available
      information, the MAG3 clearance was determined by different methods: firstly in
      an optimated whole-body technique for reference, further for comparison by means
      of a camera background-curve and a dedicated evaluating procedure, and in
      addition according to the compartmental principle (Sapirstein), by the latter
      method also simultaneously together with the hippurate clearance. Two simplified
      methods were applied as well, a non-invasive one and a single-sample method. The
      results revealed the relatively unpretentious camera technique to be nearly
      equivalent to more expensive procedures, but qualitatively superior to those
      methods, which are unnecessarily oversimplified.

PMID- 9005409
TI  - [Diagnosis of metastasis].

PMID- 9005408
TI  - [Scintigraphic evidence of silent aspiration after bilateral lung
      transplantation].
AB  - We present a case of a 25 year old patient who underwent double-sided lung
      transplantation and suffered from recurrent pneumonia. Silent aspiration was
      suspected clinically. Aspiration was proved by scintigraphy enabling to
      discriminate between direct oro-pulmonal aspiration and aspiration after gastro
      esophageal reflux.

PMID- 9005410
TI  - [Myocardial perfusion scintigraphy using 99mTC-tetrofosmin: a comparison with
      coronary angiography].
AB  - AIM: Coronary angiography is still the most reliable method for the detection of
      coronary artery disease. In this study we compared to this method the accuracy of
      99mTc-Tetrofosmin myocardial SPECT. METHOD: Fifty two patients (38 male and 14
      female) were studied with stress-rest 99mTc-Tetrofosmin myocardial SPECT. Two
      independent observers evaluated the uptake of the radiotracer using a score from
      0 to 4. All patients underwent coronary angiography and the results were compared
      to SPECT findings. We considered as hemodynamic significant any obstruction
      greater than 50% and as ischemic any myocardial region with radiotracer uptake
      less than 4 at stress. RESULTS: There was good segmental correspondence between
      tetrofosmin scintigram and angiography. Sensitivity 72.2-91.1%, specificity 80.0
      88.2%, ppv 76.4-88.5% and npv 83.3-85.7%, depending on the obstructed vessel.
      CONCLUSION: 99mTc-Tetrofosmin myocardial SPECT is a reliable alternative for the
      detection of CAD.

PMID- 9005411
TI  - [Bone SPECT of the jaws after fracture, onlay osteoplasty of insertion of
      implants].
AB  - AIM: The aim of this study was early differentiation between uncomplicated and
      complicated processes of healing in the jaw using bone SPECT. METHODS:
      Investigations were performed in 40 mandibular fractures and 26 jaws after onlay
      osteoplasty as well as secondary insertion of implants. Bone SPECT was carried
      out within 1-2 months and after approximately 4-5 months. The uptake in the jaw
      was assessed semi-quantitatively using ROI analysis. RESULTS: Fractures with
      uncomplicated healing showed a decrease of uptake in follow-up, whereas fractures
      with an infection in the later course showed an increase, resulting in a
      significantly higher uptake at the follow-up investigation for the latter group.
      1-2 months after onlay osteoplasty significantly lower uptake was found in
      regions with later occurrence of sequestration. In regions with implants in which
      osseointegration failed, there was significant reduction of uptake initially and
      significant elevation at the follow-up investigation. CONCLUSION: These results
      indicate a prognostic relevance of bone SPECT in the evaluation of processes of
      healing in the jaw.

PMID- 9005412
TI  - [Volume reduction of the thyroid after radioiodine therapy in patients with
      autonomous goiter and Basedow's goiter].
AB  - AIM: It is well known that radioiodine therapy (RITh) leads to a significant
      thyroid volume reduction (TVR). But until now only little data has been presented
      due to the course of time and the extent of TVR. METHOD: Therefore the data of 33
      patients with Graves' disease (GD), 36 patients with multifocal (MAG) and 31 with
      solitary (SAG) autonomous goitre were analyzed retrospectively. RESULTS: All the
      patients showed a highly significant (p < 0.001) TVR, which continued up to 1
      year after RITh. Receiving equal effective radiation doses, the extent of TVR was
      significantly greater for GD than for MAG. This difference developed within six
      weeks up to 3 months after RITh. CONCLUSION: This observation suggests that the
      underlying thyroid disease affects the therapeutic effect of RITh and may be
      partially explained by the total suppression of non-autonomous thyroid tissue in
      AG at the time of RITh. In patients with SAG with a 1.7 times higher effective
      radiation dose than in MAG relative TVR was about 1.6 times stronger in SAG than
      in MAG. This demonstrates a direct relation between the effective radiation dose
      and the extent of the TVR after RITh.

PMID- 9005413
TI  - [Increase in TSH levels in thyroid carcinoma patients after withdrawal of
      suppressive levothyroxine medication].
AB  - AIM: In 76 patients with thyroid carcinoma (60 f., 16 m.; age 51 +/- 15 years; 52
      with papillary, 22 with follicular, 2 with Hurthle cell thyroid carcinoma), three
      different schemes to withdraw LT4 before 131I whole body scintigraphy were
      compared. METHOD: In scheme I no interval LT3 medication is applied. Scheme II
      starts one week after withdrawal of LT4 with a two weeks lasting LT3 medication:
      40-80 micrograms LT3/die in the first week and 20 micrograms LT3/die in the
      second week. Afterwards no further LT3 medication is given. Scheme III is
      identical to scheme II in the first three weeks but 20 micrograms LT3 medication
      is continued until 131I-application. Retrospectively 121 studies were evaluated
      concerning the scheme specific increase of TSH. Factors which may influence the
      increase of TSH were analysed, i.e. age, sex, thyreoglobuline, LT4 dose, duration
      of LT4 treatment, histological type of carcinoma, result of 131I whole body
      scanning. RESULTS: There was a significant relation between increase of TSH and
      the applied scheme. Schemes with interval LT3 medication are more comfortable for
      the patient but time to stimulate TSH to values > or = 30 microIU/ml is
      prolonged, especially using scheme III. Female patients needed a significantly
      longer time compared to male patients to reach a TSH value > or = 30 microIE/ml.
      Concerning repetitive withdrawal of LT4, there was a fair intraindividual
      reproducibility of the time period from LT4 withdrawal to TSH values > or = 30
      microIE/ml. CONCLUSION: Every scheme has its specific field of indication
      depending on the compliance of the patients.

PMID- 9005414
TI  - [Relationship between properties of 131I therapy and radioiodine kinetics].
AB  - AIM: The reason of unreproducible data under diagnosis and therapy with
      radioiodine should be elucidated. METHODS: The iodine content of the capsules was
      tested by a colorimetric method and by activation analysis. Radiochemical purity
      was determined by HPLC and by electrophoresis. Solubility of the capsules was
      investigated under different conditions. RESULTS: The iodine content of the
      capsules varied between 0.8 and appr. 100 micrograms/capsule. The radiochemical
      purity of the capsule iodine varied between 75% and 99.5% (main contamination:
      iodate). The solubility of the capsules differed. CONCLUSION: Additional non
      radioactive iodine in the therapy capsules could be one reason of the reduced
      radioiodine-uptake under therapy.

PMID- 9005415
TI  - [T3 hyperthyroidism with metastatic follicular thyroid carcinoma in substitution
      therapy].
AB  - This case report shows the anamnesis of a female patient with follicular
      Thyroidglandular-Ca. in an advanced stage with multiple metastases in the
      skeletal system, lungs and hilar lymph nodes. In addition, the patient showed a
      T3 hyperthyroidism with clinical symptoms but normal to low level of T4. After
      exclusion of hormone producing metastases as a reason for the hyperthyroidism,
      the most likely explanation would be an increased 5'-deiodination from T4 to T3.

PMID- 9005416
TI  - A wait on my mind.

PMID- 9005417
TI  - A second defibrillator chest patch electrode will increase implantation rates for
      nonthoracotomy defibrillators.
AB  - Nonthoracotomy defibrillator systems can be implanted with a lower morbidity and
      mortality, compared to epicardial systems. However, implantation may be
      unsuccessful in up to 15% of patients, using a monophasic waveform. It was the
      purpose of this study to prospectively examine the efficacy of a second chest
      patch electrode in a nonthoracotomy defibrillator system. Fourteen patients (mean
      age 62 +/- 11 years, ejection fraction = 0.29 +/- 0.12) with elevated
      defibrillation thresholds, defined as > or = 24 J, were studied. The initial lead
      system consisted of a right ventricular electrode (cathode), a left innominate
      vein, and subscapular chest patch electrode (anodes). If the initial
      defibrillation threshold was > or = 24 J, a second chest patch electrode was
      added. This was placed subcutaneously in the anterior chest (8 cases), or
      submuscularly in the subscapular space (6 cases). This resulted in a decrease in
      the system impedance at the defibrillation threshold, from 72.3 +/- 13.3 omega to
      52.2 +/- 8.6 omega. Additionally, the defibrillation threshold decreased from >
      or = 24 J, with a single patch, to 16.6 +/- 2.8 J with two patches. These changes
      were associated with successful implantation of a nonthoracotomy defibrillator
      system in all cases. In conclusion, the addition of a second chest patch
      electrode (using a subscapular approach) will result in lower defibrillation
      thresholds in patients with high defibrillation thresholds, and will subsequently
      increase implantation rates for nonthoracotomy defibrillators.

PMID- 9005418
TI  - Assessing master's programs in oncology nursing.

PMID- 9005419
TI  - [Level of endothelin-1,2,6-keto-pgf1-alpha and atrial natriuretic peptide in
      serum of pregnant women with late hypertension].
AB  - The etiology of late hypertension (LH) in pregnant women is still unknown. The
      purpose of this study was to measure the circulatory levels of endothelin-1,2 (ET
      1,2), 6-keto-PGF1-alfa as a major metabolite of prostacyclin, and atrial
      natriuretic peptide (ANP) in the serum of pregnant women with LH, and in the
      serum of control healty pregnant women, and control healthy nonpregnant women.
      RESULTS: The mean level of ET-1,2 among pregnant women with LH did not show any
      significant difference compared to control group. Serum 6-keto-PGF1-alfa levels
      was significantly higher (p < 0.001) in healthy pregnant women than in those of
      the pregnant women with LH and of healthy nonpregnant women. Serum ANP was
      significantly higher (p < 0.01) in the pregnant women with LH compared to healthy
      pregnant women and healthy nonpregnant women (p < 0.001). Among the women with LH
      there was no correlation between ET-1,2, 6-keto-PGF1-alfa and ANP.

PMID- 9005420
TI  - [Anti-neutrophil cytoplasmic antibodies (ANCA) in the glomerulonephritis].
AB  - Ninety nine patients with biopsy-proven diagnosis of immunologic glomerular
      disease were included in this study: 13 with extracapillaris glomerulonephritis
      (ExGN), 38 with membranoproliferative GN (MPGN), 33 with mesangial proliferative
      GN (MesPGN), 5 with focal segmental glomerulosclerosis (FSGS), 5 with membranous
      nephropathy (MN), and 3 with minimal change nephropathy (MC). Sera of these
      patients were tested for the presence of anti-neutrophil cytoplasmic antibodies
      (ANCA) by standard indirect immunofluorescence (IIF). Specific antiproteinase 3
      (anti-Pr 3) and anti-myeloperoxidase (anti-MPO) by ELISA were assayed in ANCA
      positive patients. ANCA were detected by IIF and ELISA in sera from 28 patients
      (28%). Of the 28 patients, 3 had cytoplasmic ANCA (c-ANCA), while 25 had
      perinuclear pattern (p-ANCA). Two c-ANCA positive patients with anti-Pr3 belonged
      to group I (GN at time of diagnosis). Another c-ANCA positive patients suffering
      from GN belonged to group II (GN with restrained disease activity). Of the 25 p
      ANCA positive patients, 23 belonged to group I, 1 to group II, and I to group III
      (active GN received immunosuppressive therapy for several months). Majority of
      ANCA positive patients with GN were complicated by extrarenal organs involvement.
      One c-ANCA positive patient had ExGN and two patients had MesPGN. Of the 25 p
      ANCA positive patients, 7 had ExGN, 10 MPGN, 4 MesPGN, 2 FSGS, and 1 had MC. Five
      p-ANCA positive patients with ExGN were temporary dialysis-dependent. One of them
      died due to cardiac infarction, one became dialysis-dependent, there of them
      (treated also with plasma exchange) responded favorably to this treatment and
      after 3 to 12 months had life-sustaining renal function (s-creatinine < 265
      umol/L; < 3 mg%). Renal-limited disease had 3 p-ANCA positive patients (anti-MPO)
      with ExGN another ANCA positive patient had extrarenal organs involvement. The
      majority of patients with low titer of ANCA by IIF and low concentration p-ANCA
      by ELISA had different morphological GN, in most cases MPGN. All c-ANCA positive
      patients had extrarenal organs involvement, mainly respiratory tract. One of them
      was dialysis-dependent, and two responded favorably to immunosuppressive therapy.
      It is concluded that the IIF and ELISAs for anti-Pr3, and anti-MPO have an
      acceptable performance and are useful in the diagnostic of patients with
      vasculitis. Vasculitis can be primary in patients with pauci-immune crescentic
      GN, or secondary to other disease processes including immune complex-mediated GN.
      IS treatment (methylpredisolone + cyclophospamide) of ANCA positive patients with
      renal insufficiency nad normal or enlarged renal size is favourable. In the
      patients with extrarenal organs involvement and without improvements in renal
      function, however, requirement of plasma exchange is considered.

PMID- 9005421
TI  - [Relationship between fasting glycemia, serum peptide C, insulin, growth hormone
      and plasma glucagon in acromegaly].
AB  - The aim of this study was to investigate interrelations among fasting glycaemia,
      serum C-peptide, insulin, growth hormone and plasma glucagon concentration in
      people with acromegaly. 22 patients with active acromegaly, 11 women and 11 men
      (group A) and 19 healthy people (group K) participated in the study. The oral
      glucose tolerance test was carried out in all participants. Blood glucose, serum
      C-peptide, growth hormone and plasma glucagon concentration was measured. 13
      patients with acromegaly had normal glucose tolerance (group AT) and 9 had
      impaired glucose tolerance (group AN). Statistical analysis was performed using
      Student's test and regression analysis. The comparison of patients from group A
      and K showed, that serum growth hormone, C-peptide, insulin, blood glucose
      concentration in fasting state was higher in acromegaly. There were no
      differences in fasting plasma glucagon concentration between both groups. Fasting
      glycaemia was similar in patients AT and controls, but there were also higher
      fasting serum C-peptide and insulin concentrations in the AT group. Fasting blood
      glucose, serum C-peptide and insulin concentration was higher in AN group than in
      controls. There were no significant differences in the above parameters between
      AT and AN group. Analysis of regression showed the negative correlation of
      fasting serum growth hormone and blood glucose concentration in the group A and
      AT. However there was no correlation between other parameters and fasting
      glycaemia, in particular between fasting glycaemia and insulin concentration.
      Fasting glycaemia positively correlated with fasting serum insulin concentration
      in healthy men. The comparison of glycaemia and fasting concentration of some
      hormones in patients with acromegaly regarding their glucose tolerance, did not
      answer the question, which hormonal abnormality is the most specific for
      disturbances of carbohydrate metabolism in acromegaly. Therefore groups of
      patients with markedly high of hormones in fasting state concentrations were
      distinguished. There was no difference in fasting glycaemia in this people
      compared to patients with normal or moderately elevated concentrations of
      hormones studied. CONCLUSIONS: There is higher fasting glycaemia in patients with
      acromegaly compared to healthy men. Among them one can see subjects with normal
      glucose tolerance that is accompanied with high serum C-peptide and insulin
      concentration. Disturbances of glucose-insulin interregulation occur in these
      people.

PMID- 9005422
TI  - [Primary hyperparathyroidism--diagnostic problems].
AB  - Parathyroid imaging with 99m Tc-MIBI, introduced at the beginning of the 90's
      seems to be a promising method for parathyroid adenomas localization. The aim of
      the study was to assess the efficacy of parathyroid imaging with 99m Tc-MIBI for
      preoperative localization of parathyroid adenomas and to compare that method with
      the high-resolution ultrasonography. Thirteen patients with primary
      hyperparathyroidism of duration from 2 to 25 years were included in the study.
      The presence of parathyroid adenomas was confirmed by histopathology in all
      patients. The sensitivity for scintigraphy and ultrasonography was 92.8% and
      78.5%, the number of false positive results was 0 and 2 and false negative-0 and
      1, respectively. Parathyroid imaging with 99m Tc-MIBI is a useful method for
      parathyroid adenomas localization, and in contrast to ultrasonography its
      sensitivity does not decrease if a parathyroid adenoma is located ectopically.
      Nevertheless, because of the greater accessibility, lower costs and its
      simplicity ultrasonography should be used as a screening modality for parathyroid
      adenoma localization.

PMID- 9005423
TI  - [Effect of age and sex on the occurrence of gastritis changes in gastric mucosa].
AB  - Natural course of gastritis is far from being clarified. Having this fact in mind
      we undertook this study to establish how age and sex did influence the frequency
      and intensity of inflammation in particular stomach portions. Possible relation
      between gastritis on the one hand and cholelithiasis and idiopathic non-ulcer
      dyspepsia on the other was also checked. The study comprised 392 persons,
      including 148 subjects with cholelithiasis, 130 with non-ulcer dyspepsia and 114
      healthy volunteers. Endoscopy of upper digestive tract was done in all of them,
      the specimens of mucosa of gastric antrum and body being taken for histologic
      examination. Frequency of gastritis was found to rise with age, particularly up
      to the 40-th year of life, being analogical in both sexes. In men, gastritis
      showed higher intensity and activity as well as more rapid progression toward
      glandular atrophy. In particular age intervals no significant difference in the
      frequency of gastritis was found between the population of healthy persons, that
      suffering from cholelithiasis as well as that with non-ulcer dyspepsia.

PMID- 9005424
TI  - [Fibrosigmoidoscopy as a screening method for colorectal neoplasms in a
      population of patients hospitalized in the internal medicine department].
AB  - Surgical treatment of an early enough diagnosed large bowel cancer is possible in
      the screening tests. Fibrosigmoidoscopy is a sensitive method of the neoplastic
      lesions' diagnostics in the distal large bowel and competes the tests for occult
      blood in stools. The aim of the study was the assessment of fibrosigmoidoscopy as
      a screening test in a hospitalized patients. 2405 hospitalized patients were
      analysed in 2 years. Fibrosigmoidoscopy was performed in 903. Polyps, mainly
      neoplastic were diagnosed in 115 patients and cancers in 4 cases. The percentage
      of the results in other countries. The acceptance of the method was high (86%).
      We suggest that fibrosigmoidoscopy should be performed as the screening test in
      the hospitalized population.

PMID- 9005425
TI  - [Sneddon syndrome].
AB  - There is presented a case a 42 year old woman, who was admitted to the Department
      of Internal Diseases, the Institute of Dentistry, Medical Academy in Warsaw, with
      suspected bacterial endocarditis. Two episodes which indicate a lesion in the
      central nervous system (as right side hemiparesis and mixed aphasia) in the
      patients with valvular heart disease, were the basis of this suspicion. Bacterial
      endocarditis was not confirmed during hospitalisation. Diagnosis of Sneddon's
      syndrome was established based on skin lesion of livedo reticulatis type with
      typical picture in skin biopsy and on the lesions in the central nervous system
      confirmed by MRI. Moreover the patients had arterial hypertension and Raynaud's
      syndrome. We presented the diagnostic difficulties of Sneddon's syndrome, a
      course of the disease, the factors, which affect its prognosis and attempts to
      treat this syndrome based on this case.

PMID- 9005426
TI  - [Diagnostic difficulties in acute intermittent porphyria. Report of two cases].
AB  - Two patient with acute intermittent porphyria with dominating neurological
      symptoms were described. Both patients were initially diagnosed and treated as
      Guillain-Barre syndrome. Diagnostic mistakes took place because of the lack of
      abdominal symptoms coexisting usually with the neurological and psychiatric
      features. Therefore the investigation of the urine level of PBG and ALA was not
      done. We also would like to point out that acute abdominal pain in a patient with
      porphyria may have other causes than porphyric attack.

PMID- 9005427
TI  - [Exercise rehabilitation in patients with heart failure--palliation or disease
      modification?].

PMID- 9005428
TI  - [Regulation of natriuresis in diabetic nephropathy].

PMID- 9005429
TI  - [Uremic myopathy].

PMID- 9005430
TI  - [Minimal residual disease in acute leukemias. Optimal method of detection].

PMID- 9005431
TI  - A novel binding site in catalase is suggested by structural similarity to the
      calycin superfamily.

PMID- 9005432
TI  - Simulation of a complex protein structural change: the T <--> R transition in the
      insulin hexamer.
AB  - The T <--> R transition in the insulin hexamer is an outstanding model for
      protein structural changes in terms of its extent and complexity: the limiting
      structures T(6), T(3)R(3) and R(6) have been defined by X-ray crystallography.
      The transition occurs cooperatively within trimers. It involves displacements of
      >30 A and a secondary structural rearrangement of 15% of the peptide chain
      between extended and helical conformations. Experimental data for the transition
      are plentiful. Theoretical methods to simulate pathways without constraints would
      never succeed with such substantial transitions. We have developed two
      approaches, targeted energy minimization (TEM) and targeted molecular dynamics
      (TMD). Previously successful in simulating the T <--> R transition of the insulin
      monomer, these procedures are also shown here to be effective in the hexamer.
      With TMD, more conformational space is explored and pathways are found at 500
      kJ/mol lower energy than with TEM. Because the atoms have to meet distance
      constraints in sum rather than individually, a high degree of conformational
      freedom and independence is implied. T(6) --> T(3)R(3) and T(3)R(3) --> T(6)
      pathways do not coincide because the transformation is directed. One subunit
      enters a dead end pathway in one direction of the TMD simulation, which shows
      that constraint and freedom are critically balanced. The ensemble of productive
      pathways represents a plausible corridor for the transition. A video display of
      the transformations is available.

PMID- 9005433
TI  - Quantifying the local reliability of a sequence alignment.
AB  - We present a method for attributing a measure of reliability to a residue pair in
      an optimal alignment of two protein sequences. Validation based on a database of
      structurally correct alignments [Pascarella and Argos (1992) Protein Engng, 5,
      121-137] shows that correctly aligned parts of a sequence alignment
      systematically receive high scores in this measure. The higher the sequence
      similarity between two sequences, the larger is the fraction found of the correct
      parts of the alignment. We used these observations to design a program that draws
      a reliability curve along an optimal alignment reflecting the chances for each
      residue pair to be aligned correctly.

PMID- 9005434
TI  - Incorporation of non-local interactions in protein secondary structure prediction
      from the amino acid sequence.
AB  - Existing approaches to protein secondary structure prediction from the amino acid
      sequence usually rely on the statistics of local residue interactions within a
      sliding window and the secondary structural state of the central residue. The
      practically achieved accuracy limit of such single residue and single sequence
      prediction methods is 65% in three structural stages (alpha-helix, beta-strand
      and coil). Further improvement in the prediction quality is likely to require
      exploitation of various aspects of three-dimensional protein architecture. Here
      we make such an attempt and present an accurate algorithm for secondary structure
      prediction based on recognition of potentially hydrogen-bonded residues in a
      single amino acid sequence. The unique feature of our approach involves database
      derived statistics on residue type occurrences in different classes of beta
      bridges to delineate interacting beta-strands. The alpha-helical structures are
      also recognized on the basis of amino acid occurrences in hydrogen-bonded pairs
      (i,i + 4). The algorithm has a prediction accuracy of 68% in three structural
      stages, relies only on a single protein sequence as input and has the potential
      to be improved by 5-7% if homologous aligned sequences are also considered.

PMID- 9005435
TI  - Modelling constrained calcitonin gene-related peptide analogues.
AB  - The calcitonin gene-related peptide (CGRP) is a 37-residue peptide with
      pronounced physiological activities, making it an interesting lead for drug
      development. In our previous work, we designed constrained analogues of the
      peptide. The biological activities of these proved that the disulfide bridges
      created favoured the active conformations of the peptide. Here we report the
      molecular modelling of the conformation of domains involved in receptor
      activation. Our approach was to create sets of possible conformations for three
      differently constrained bioactive regions by a random search of conformational
      space and molecular modelling. The conformations were compared, and those allowed
      for all derivatives were considered relevant for receptor activation. This
      approach resulted in one favoured group of conformations characterized by an
      inverse gamma-turn followed by a gamma-turn, defining the conformation of the
      tripeptide region with a similar sequence in all active analogues. The models may
      also be used for the design of peptide and non-peptide analogues of CGRP.

PMID- 9005436
TI  - Molecular modelling of UH-301 and 5-HT(1a) receptor interactions.
AB  - A three-dimensional model of the human 5-HT(1a) receptor was constructed by
      molecular modelling, and the molecular and electronic structures of (R)- and (S)
      5-fluoro-8-hydroxy-2-(dipropylamino)tetralin (UH-301) and of (R)- and (S)-8
      hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) were examined by molecular
      mechanics and quantum mechanics calculations and molecular dynamics simulations.
      The receptor model has seven transmembrane alpha-helices (TMHs), organized
      according to a projection map of visual rhodopsin, and includes all loops between
      helices and the N- and C-terminal parts. Interactions of UH-301 and 8-OH-DPAT
      with the 5-HT(1a) receptor were examined by molecular dynamics simulations and
      energy minimization of receptor-ligand complexes. 8-OH-DPAT had lower
      electrostatic potentials around the hydroxyl group and stronger hydrogen bonding
      to the receptor model than had UH-301. The simulations indicated that the 5
      HT(1a) receptor agonists, (R)- and (S)-8-OH-DPAT and (R)-UH-301, interacted with
      the receptor at a site closer to Asp82 in TMH2 than did (S)-UH-301, which is a 5
      HT1a receptor antagonist. Simulations of receptor-ligand complexes indicated that
      Asp82, Asp116, Serl99, Thr2OO and Ile385 are essential for binding of both
      agonist and antagonist to the receptor.

PMID- 9005437
TI  - Molecular modelling of Staphylococcal delta-toxin ion channels by restrained
      molecular dynamics.
AB  - Delta-Toxin is a 26-residue channel-forming peptide from Staphylococcus aureus
      which forms an amphipathic alpha-helix in a membrane environment. Channel
      formation in planar bilayers suggests that an average of six delta-toxin helices
      self-assemble to form transbilayer pores. Molecular models for channels formed by
      delta-toxin and by a synthetic analogue have been generated using a simulated
      annealing protocol applied via restrained molecular dynamics. These models are
      analysed in terms of the predicted geometric and energetic properties of the
      transbilayer pores. Pore radius calculations of the models demonstrate that rings
      of channel-lining residues contribute a series of constrictions along the pore.
      Electrostatic properties of the pores are determined both by pore-lining charged
      side chains and by the aligned helix dipoles of the parallel helix bundle.
      Molecular dynamics simulations (100 ps) of delta-toxin models containing intra
      pore water were performed. Analysis of the resultant dynamics trajectories
      further supports the proposal that alternative conformations of pore-constricting
      side chains may be responsible for the observed conductance heterogeneity of
      delta-toxin ion channels.

PMID- 9005439
TI  - Structural and functional properties of mutant Arg203Pro from yeast
      phosphoglycerate kinase, as a model of phosphoglycerate kinase-Uppsala.
AB  - A pathological variant of human phosphoglycerate kinase, phosphoglycerate kinase
      Uppsala, associated with chronic nonspherocytic hemolytic anemia has been found
      to differ from the normal enzyme by substitution of an arginine at position 206
      (corresponding to position 203 in yeast) by a proline. In order to understand the
      structural and functional consequences of this mutation, the corresponding mutant
      in yeast phosphoglycerate kinase was constructed. The three-dimensional structure
      of this mutant was resolved at 2.9 A. Although the overall structure is not
      modified, small local changes were observed. The kinetic parameters of the mutant
      were not found to be greatly affected, the catalytic constant being lowered by
      only 10-20%. The most significant difference when compared with the wild-type
      enzyme is a decrease in stability by about 3 kcal/mol. The physiological
      implications of this instability are discussed.

PMID- 9005438
TI  - FK506-binding protein mutational analysis: defining the active-site residue
      contributions to catalysis and the stability of ligand complexes.
AB  - The 12 kDa FK506-binding protein FKBP12 is a cis-trans peptidyl-prolyl isomerase
      that binds the macrolides FK506 and rapamycin. We have examined the role of the
      binding pocket residues of FKBP12 in protein-ligand interactions by making
      conservative substitutions of 12 of these residues by site-directed mutagenesis.
      For each mutant FKBP12, we measured the affinity for FK506 and rapamycin and the
      catalytic efficiency in the cis-frans peptidyl-prolyl isomerase reaction. The
      mutation of Trp59 or Phe99 generates an FKBP12 with a significantly lower
      affinity for FK506 than wild-type protein. Tyr26 and Tyr82 mutants are
      enzymatically active, demonstrating that hydrogen bonding by these residues is
      not required for catalysis of the cis-trans peptidyl-prolyl isomerase reaction,
      although these mutations alter the substrate specificity of the enzyme. We
      conclude that hydrophobic interactions in the active site dominate in the
      stabilization of FKBP12 binding to macrolide ligands and to the twisted-amide
      peptidyl-prolyl substrate intermediate.

PMID- 9005440
TI  - Peroxynitrite modification of glutathione reductase: modeling studies and kinetic
      evidence suggest the modification of tyrosines at the glutathione disulfide
      binding site.
AB  - The catalytic properties of glutathione reductase for its substrate, glutathione
      disulfide, were altered following a 60 s exposure to a 100-fold molar excess of
      peroxynitrite; the K(M) value was increased by approximately 2.5-fold and the
      V(max) value was decreased by approximately 1.7-fold. The kinetic alterations are
      thought to result from nitrotyrosine formation as the intrinsic Tyr fluorescence
      is diminished. The UV-visible spectrum of glutathione reductase exhibited
      absorbance at approximately 423 nm, characteristic of nitrotyrosine. In addition,
      the presence of nitrotyrosine has been detected by Western immunoblots with an
      anti-nitrotyrosine antibody. The peroxynitrite-induced inactivation is not
      observed in the presence of excess glutathione disulfide. However, excess NADPH
      offered no protection against peroxynitrite-induced inactivation. These
      observations suggest that the modification of approximately 1.8 Tyr per subunit,
      at or near the glutathione disulfide binding domain, probably results in the
      observed catalytic alterations. To test this hypothesis, the two tyrosines
      closest to the glutathione disulfide binding domain (Tyr114 and Tyr106), as
      indicated by the X-ray crystallographic data [Karplus and Schulz (1989) J. Biol.
      Chem., 210, 163-180], were each converted to nitrotyrosines by molecular modeling
      and the structure energy was minimized. These theoretical calculations indicate
      that the bond lengths between Tyr114-O and the Gly-N and Cys II-N of glutathione
      disulfide bound to glutathione reductase (Karplus and Schulz, 1989) increased by
      3.0 and 4.3 A, respectively, upon nitration. In the case of Tyr106 the 0-Cys II-N
      distance also increases by approximately 1.6 A. The loss of these hydrogen
      bonding contacts is likely to result in the observed catalytic alterations upon
      reaction with peroxynitrite.

PMID- 9005441
TI  - The de novo protein with grafted biological function: transferring of interferon
      blast-transforming activity to albebetin.
AB  - The de novo protein albebetin has been designed recently to form a predetermined
      tertiary fold that has not yet been observed in natural proteins. An eight amino
      acid fragment (131-138) of human interferon alpha(2) carrying the blast
      transforming activity of the protein was attached to the N-terminus of albebetin
      next to its initiatory methionine residue. The gene of chimeric protein was
      expressed in a wheat germ cell-free translation system and synthesized protein
      was tested for its compactness and stability. Its ability for receptor binding
      was also studied. We have shown that albebetin with attached octapeptide is
      practically as compact as natural proteins of corresponding molecular weight and
      possesses high stability toward the urea-induced unfolding. It binds murine
      thymocyte receptor at a high affinity and activates the thymocyte blast
      transformation efficiently at a concentration of 10(-11) M.

PMID- 9005442
TI  - Affinity enhancement of a recombinant antibody: formation of complexes with
      multiple valency by a single-chain Fv fragment-core streptavidin fusion.
AB  - In antigen-antibody interactions, the high avidity of antibodies depends on the
      affinity and number of the individual binding sites. To develop artificial
      antibodies with multiple valency, we have fused the single-chain antibody Fv
      fragments to core streptavidin. The resulting fusion protein, termed scFv::strep,
      was found after expression in Escherichia coli in periplasmic inclusion bodies.
      After purification of the recombinant product by immobilized metal affinity
      chromatography, refolding and size-exclusion FPLC, tetrameric complexes
      resembling those of mature streptavidin were formed. The purified tetrameric
      scFv::strep complexes demonstrated both antigen- and biotin-binding activity,
      were stable over a wide range of pH and did not dissociate at high temperatures
      (up to 70 degrees C). Surface plasmon resonance measurements in a BIAlite system
      showed that the pure scFv::strep tetramers bound immobilized antigen very tightly
      and no dissociation was measurable. The association rate constant for scFv::strep
      tetramers was higher than those for scFv monomers and dimers. This was also
      reflected in the apparent constants, which was found to be 35 times higher for
      pure scFv::strep tetramers than monomeric single-chain antibodies. We could also
      show that most of biotin binding sites were accessible and not blocked by
      biotinylated E.coli proteins or free biotin from the medium. These sites should
      therefore facilitate the construction of bispecific multivalent antibodies by the
      addition of biotinylated ligands.

PMID- 9005443
TI  - Construction and structure-activity relationships of chimeric prourokinase
      derivatives with intrinsic thrombin-inhibitory potential.
AB  - The blood clotting enzyme thrombin plays a central role in the aetiology of
      occlusive disorders such as stroke and acute myocardial infarction. During
      fibrinolytic therapy with plasminogen activators, thrombin is neutralized by
      anticoagulative drugs. In order to combine plasminogen-activating and thrombin
      inhibitory activities we constructed chimeric derivatives of recombinant single
      chain, urokinase-type plasminogen activator (rscu-PA) which comprise the kringle
      and protease domain of rscu-PA fused via a linker sequence to a thrombin
      inhibitory domain. The inhibitory domain contains a sequence element directed to
      the active site of thrombin and a sequence taken from either hirudin or the human
      thrombin receptor both binding to the fibrinogen recognition site of thrombin.
      Analysing different sets of point mutants showed that the linker between the
      protease domain and the active site-directed sequence is contributing
      significantly to the thrombin-inhibitory potential. Kinetic analysis of thrombin
      inhibition revealed that most of the chimeras tested competitively inhibit the
      thrombin-mediated cleavage of a peptide substrate in a concentration-dependent
      manner; however, in two examples the insertion of one glycine residue into the
      active site directed-sequence abolished the blockade of the active site. This
      supports the conclusion that the chimeras with high thrombin-inhibitory potential
      interact with the active site and the fibrinogen recognition site of thrombin.

PMID- 9005444
TI  - Multimer formation as a consequence of separate homodimerization domains: the
      human c-Jun leucine zipper is a transplantable dimerization module.
AB  - Human c-Jun and c-Fos leucine zipper domains were examined for their ability to
      serve as autonomous dimerization domains as part of a heterologous protein
      construct. Schistosoma japonicum glutathione S-transferase (GST) was fused to
      recombinant Jun leucine zipper (rJunLZ) and Fos leucine zipper (rFosLZ) domains.
      SDS-PAGE 'snapshot' analyses based on disulphide linkage of monomers demonstrated
      the ability of rJunLZ to function as a dimerization motif in a foreign protein
      environment. Steric hindrance prevented formation of rJunLZ-GST::rFosLZ-GST
      heterodimers whereas rJunLZ-GST::rFosLZ and rJunLZ:: rFosLZGST formed readily.
      Furthermore, rJunLZGST generated homodimers suggesting fusion protein
      heterodimers interact differently to homodimers. Gel filtration chromatography
      confirmed that GST is a dimer in solution and that attachment of a leucine zipper
      domain allows further interactions to take place. Sedimentation equilibrium
      analyses showed that GST is a stable dimer (K(a) > 10(6) M(-1)) with no higher
      multimeric forms. rFosLZ-GST weakly associates beyond a dimer (K(a) approximately
      4 x 10(4) M(-1)) and rJunLZ-GST associates indefinitely (K(a) approximately 4 x
      10(5) M(-1)) [corrected], consistent with an isodesmic model of association. The
      interaction of these leucine zippers independently of GST association
      demonstrates their utility in the modification of proteins when multimer
      formation is desired.

PMID- 9005445
TI  - Destabilizing interactions between the partners of a bifunctional fusion protein.
AB  - Hybrid MalE-GVP is a bifunctional protein in vitro since it binds maltose as
      protein MalE of Escherichia coli and since it is dimeric and specifically binds
      single-stranded DNA as protein GVP of phage M13. The oxidation rate of a unique
      cysteine residue was used to compare the stabilities of GVP in its free and
      hybrid forms, under conditions where MalE was either folded or unfolded by a
      denaturing agent. The results showed that both the covalent link and tertiary non
      covalent interactions between MalE and GVP destabilized GVP in MalE-GVP. To test
      whether GVP had identical structures in its free and hybrid forms, mutations were
      used as local conformational probes. The effects of these mutations on the
      capabilities of MalE-GVP to dimerize and to bind single-stranded DNA were assayed
      in vitro. They were compatible with the effects of the same mutations on the
      global activity of free GVP in vivo and with the effects that could be predicted
      from the known data on free GVP, in particular its crystal structure. Thus, one
      partner of a hybrid protein can be destabilized by the other partner while
      maintaining its structural and functional characteristics.

PMID- 9005446
TI  - Display of beta-lactamase on the Escherichia coli surface: outer membrane
      phenotypes conferred by Lpp'-OmpA'-beta-lactamase fusions.
AB  - Bacterial cell-surface exposure of foreign peptides and soluble proteins has been
      achieved recently by employing a fusion protein methodology. An Lpp'-OmpA(46-159)
      Bla fusion protein has been shown previously to display the normally periplasmic
      enzyme beta-lactamase (Bla) on the cell surface of the Gram-negative bacterium
      Escherichia coli. Here, we have investigated the role of the OmpA domain of the
      tripartite fusion protein in the surface display of the passenger domain (Bla)
      and have characterized the effects of the fusion proteins on the integrity and
      permeability of the outer membrane. We show that in addition to OmpA(46-159), a
      second OmpA segment, consisting of amino acids 46-66, can also mediate the
      display of Bla on the cell surface. Other OmpA domains of various lengths (amino
      acids 46-84, 46-109, 46-128, 46-141 and 46-145) either anchored the Bla domain on
      the periplasmic face of the outer membrane or caused a major disruption of the
      outer membrane, allowing the penetration of antibodies into the cell. Detergent
      and antibiotic sensitivity and periplasmic leakage assays showed that changes in
      the permeability of the outer membrane are an unavoidable consequence of
      displaying a large periplasmic protein on the surface of E. coli. This is the
      first systematic report on the effects that cell surface engineering may have on
      the integrity and permeability properties of bacterial outer membranes.

PMID- 9005447
TI  - The role of wide-spectrum cytokeratin staining of the bone marrow cores in
      patients with ductal carcinoma of the breast.
AB  - The usefulness of routine pancytokeratin staining of bone marrow cores (BMCs)-
      negative for hematoxylin and eosin (HE)--from patients with lobular carcinoma of
      the breast has been fairly well established. However, the role of wide-spectrum
      cytokeratin staining of HE-negative BMCs from patients with ductal carcinoma has
      not been as well determined and is the purpose of this study. Forty-two
      prospectively and retrospectively reviewed He-negative BMCs from 21 patients with
      ductal breast carcinoma failed to reveal staining with a wide-spectrum
      cytokeratin stain, supporting the selective use of this immunostain in
      "suspicious" cases with atypical cells detected in HE BMCs.

PMID- 9005448
TI  - The N-terminal domain of a K+ channel beta subunit increases the rate of C-type
      inactivation from the cytoplasmic side of the channel.
AB  - Voltage-gated K+ channels are complexes of membrane-bound, ion-conducting alpha
      and cytoplasmic ancillary (beta) subunits. The primary physiologic effect of
      coexpression of alpha and beta subunits is to increase the intrinsic rate of
      inactivation of the alpha subunit. For one beta subunit, Kv beta 1.1,
      inactivation is enhanced through an N-type mechanism. A second beta subunit, Kv
      beta 1.2, has been shown to increase inactivation, but through a distinct
      mechanism. Here we show that the degree of enhancement of Kv beta 1.2
      inactivation is dependent on the amino acid composition in the pore mouth of the
      alpha subunit and the concentration of extracellular K+. Experimental conditions
      that promote C-type inactivation also enhance the stimulation of inactivation by
      Kv beta 1.2, showing that this beta subunit directly stimulates C-type
      inactivation. Chimeric constructs containing just the nonconserved N-terminal
      region of Kv beta 1.2 fused with an alpha subunit behave in a similar fashion to
      coexpressed Kv beta 1.2 and alpha subunit. This shows that it is the N-terminal
      domain of Kv beta 1.2 that mediates the increase in C-type inactivation from the
      cytoplasmic side of the pore. We propose a model whereby the N terminus of Kv
      beta 1.2 acts as a weakly binding "ball" domain that associates with the
      intracellular vestibule of the alpha subunit to effect a conformational change
      leading to enhancement of C-type inactivation.

PMID- 9005450
TI  - Benzophenanthridine alkaloids of Chelidonium majus; I. Inhibition of 5- and 12
      lipoxygenase by a non-redox mechanism.
AB  - The benzophenanthridine alkaloids sanguinarine and chelerythrine of Chelidonium
      majus, L. (Papaveraceae), are potent inhibitors of 5-lipoxygenase in
      polymorphonuclear leukocytes and 12-lipoxygenase in mouse epidermis, while the
      activity of soybean lipoxygenase is not influenced. The extract of the herb of
      Ch.majus also inhibits the 5-LO enzyme. Chelidonine, which cannot form
      pseudobases, is inactive against LO enzymes. Pro- and antioxidant actions of
      benzophenanthridine alkaloids can be excluded from the lack of deoxyribose
      degradation, reactivity against free radicals and inhibition of lipid
      peroxidation, suggesting that the inhibitory effects against LO enzymes appear to
      be due to specific enzyme interaction rather than a nonspecific redox mechanism.

PMID- 9005449
TI  - Chemical and biological investigation of the root bark of Clerodendrum
      mandarinorum.
AB  - A 70% EtOH extract of Clerodendrum mandarinorum root bark was assessed for CNS
      activity against 18 radioligand receptor binding assays. The results showed that
      the extract was able to bind to opiate, adenosine-1, alpha 2-adrenergic, 5HT-1,
      5HT-2, dopamine-2, histamine-1, GABA(A), and GABA(B) receptors. Fourteen
      compounds were isolated and identified by El-MS, 1H-NMR and 13C-NMR spectra as
      known triterpenoids (friedelanone, lupeol, betulinic acid), steroids (24S
      stigmata-5,25-dien-3 beta-ol,22E,24S-stigmata-5,22,25-trien-3 beta-ol),
      flavonoids (cirsimaritin, cirsimaritin-4'-glucoside, quercetin-3-methyl ether),
      tetra-hydro-alpha-pyrone and saccharides (sucrose, alpha-D- and beta-D
      glucopyranose, ethyl-alpha-D-glucopyranoside, 2-ethyl-beta-D-fructofuranoside).
      The isolated compounds were assessed for activity by the radioligand receptor
      binding assays. Betulinic acid and ethyl-alpha-D-glucopyranoside showed weak
      activities against sulphonylureas (IC50 = 7.5 microM) and muscarinic receptors
      (IC50 = 5.5 microM), respectively. Cirsimaritin-4'-glucoside was weakly active in
      the adenosine-1 binding assay (IC50 = 3.0 microM), whereas seven structurally
      related flavonoids, not isolated from C.mandarinorum, were inactive.

PMID- 9005451
TI  - Scavenging effect of tetrandrine of active oxygen radicals.
AB  - The scavenging effects of tetrandrine (TD) on active oxygen radicals were
      investigated through chemiluminescence experiments and oxidation of
      ferrocytochrome c. The superoxide anions (O2-.) were generated either in
      hypoxanthine/xanthine oxidase (HX-XOD) system or by means of auto-oxidation of
      erythrocytes. It was found that TD (7.5 microM) could remarkably scavenge O2-. in
      the HX-XOD system and that the effect was concentration-dependent. The scavenging
      effect of TD on O2-. generated from auto-oxidation in erythrocytes was not as
      strong as in the HX-XOD system. The hydroxyl radicals (.OH) were generated in
      aqueous solution of H2O2 irradiated by UV, it was also found that TD (15 microM)
      effectively scavenged .OH in that system. This study led to the conclusion that
      the antioxidant property of TD may account for some of its pharmacological
      effects.

PMID- 9005452
TI  - Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, beta
      caryophyllene.
AB  - The gastric cytoprotective effect of beta-caryophyllene, an anti-inflammatory
      sesquiterpene, was investigated in rats. The oral administration of beta
      caryophyllene to rats significantly inhibited gastric mucosal injuries induced by
      necrotizing agents such as absolute ethanol and 0.6 N HCl, although it failed to
      prevent water immersion stress- and indomethacin-induced gastric lesions. In
      addition, this compound hardly affected the secretion of gastric acid and pepsin.
      Thus, beta-caryophyllene elicited anti-inflammatory effects without any
      indication of gastric mucosal damage typical of non-steroidal anti-inflammatory
      agents. Furthermore, this compound manifested cytoprotective effects, rendering
      the two-dimensional efficacious beta-caryophyllene to be a clinically safe and
      potentially useful agent.

PMID- 9005454
TI  - The value of the baccalaureate degree.

PMID- 9005453
TI  - Presaccadic attention allocation and express saccades.
AB  - Express saccades are visually-guided saccades that are characterized by an
      extremely short latency of about 100 ms. The present experiments tested the
      hypothesis that a disengagement of visual attention is necessary for the
      generation of express saccades. All subjects produced large numbers of express
      saccades in the gap paradigm, in which the fixation stimulus is removed 200 ms
      before target onset (Exp. 1), but not in the overlap paradigm, in which the
      fixation stimulus remained on during the entire trial (Exp. 2). By means of
      peripheral cues (Exps. 3-5) and central cues (Exps. 6-7), visual attention was
      directed at the target location for the saccade before the actual appearance of
      the saccade target. In all experiments, the location cues facilitated rather than
      abolished express saccades. The generation of express saccades was facilitated
      even when the currently fixated visual stimulus was not removed before target
      onset (fixation-overlap; Exps. 5-7). The results are explained by the hypothesis
      that a disengagement of a separate fixation system is necessary for the
      generation of express saccades, a hypothesis that is in line with current
      neurobiological findings.

PMID- 9005455
TI  - Patient interviews: the heart of the exam.

PMID- 9005456
TI  - [Evaluation of methods for radiographic measurement of the tibial slope. A study
      of 83 healthy knees].
AB  - PURPOSE OF THE STUDY: We compared on lateral X-rays of 83 healthy knees, 6
      methods measuring the tibial sagittal slope. Each method determined the tibial
      slope according to an independent anatomical axis. The goals of the study were
      to: 1) detect the differences between the 6 methods; 2) determine if any
      mathematical relation could be observed between the 6 methods; 3) compare
      accuracy of proximal anatomical axis versus long anatomical axis to evaluate the
      tibial slope. MATERIAL: 50 healthy patients (83 knees) knees were included in the
      study. The patients (26 male and 24 females) were 39.3 +/- 15.8 years old.
      METHODS: We obtained true lateral X-rays orientated with an image intensifier in
      order to obtain the exact superposition of the femoral condyles. The measurements
      were carried out by an observer according to two procedures: 1) by manual
      goniometric measurements twice; the mean value between both lectures was
      recorded; 2) with a digitizer (Orthographics TM, Salt Lake City, Ut). We measured
      the angle between the tangent to the medial tibial plateau and the perpendicular
      direction to each of the studied anatomical axis: tibial proximal anatomical axis
      (TPAA); tibial shaft anatomical axis (TSAA); posterior tibial cortex (PTC);
      fibular proximal anatomical axis (FPAA); fibular shaft axis (FSA); anterior
      tibial cortex (ATC). The values obtained with the digitizer were used to compare
      the six methods. The values obtained with the TSAA were considered as reference.
      RESULTS: Tibial slope values were different with the 6 methods. ATC gave the
      higher values and PTC the smaller. The difference could be 5 degrees between two
      methods measuring the same posterior tibial slope. However different, the values
      obtained with the 6 methods were strongly correlated (R > 0.85; p = 0.0001). We
      determined mathematical relationships between the values obtained with the 6
      methods according to the regression analysis. The correlation with the values
      obtained with TSAA (reference values) was stronger for TPAA and TPC (respectively
      R = 0.92 and R = 0.9). The mean error between manual and digitized measurements
      was 1.28 degrees, but for the same knee the error could exceed 4 degrees. The
      highest error was 4.64 degrees with the TSAA, likewise the error frequency was
      higher with the TSAA (12 knees with an error > 3 degrees versus 7 knees for the
      other methods (p = 0.01)). In our 33 bilateral knees, after one side measurement,
      the forecast of the contralateral tibial slope showed an error of 5 degrees or
      more in 5 patients (15.1 per cent) and an error of 3 degrees or more in 13
      patients (39.3 per cent). Among the proximal anatomical axis, only the TPAA and
      the TPC were not influenced by age, sex, patient height or weight. CONCLUSION:
      Values of posterior tibial slope observed with the 6 methods were different but
      correlated. Among the proximal axis, the TPAA and PTC gave higher reliability.
      The values obtained with these two methods: 1) were not influenced by
      morphometric variables, 2) were strongly correlated with the references values
      obtained with the TSAA, 3) gave low error with manual measurements by comparing
      with digitized measurements. Forecast of the contralateral tibial slope after one
      side measurement is unreliable. Satisfactory accuracy could be obtained with a
      two times manual goniometric measurement, but using a digitizer improves
      measurement accuracy and is less time consuming.

PMID- 9005457
TI  - [Selective indications of skull radiography after head injury in children].
AB  - PURPOSE OF THE STUDY: Skull X-rays are systematically performed on children after
      head injuries in most hospitals. However, the discovery of a skull fracture as an
      isolated finding rarely warrants intervention. In february 1994, we stopped
      performing systematical skull X-rays in children after head injuries. We report
      the results of this experience. MATERIALS AND METHODS: Since February 1994, only
      children with possible skull penetration, depressed fracture, or presenting signs
      of basilar fracture had X-ray examination. Facial injuries were excluded in this
      study. In case of focal neurologic signs, neurosurgical consultation, or
      emergency CT examination, or both were performed. In case of change of
      consciousness at the time of injury or subsequently, the child was hospitalised
      for clinical observation for 48 hours, but no X-ray examination was performed.
      Children without any neurological signs or change of consciousness were
      discharged to their homes after they were given a head-injury instruction sheet,
      and if a second person could observe them for signs indicating that they belong
      to a higher risk group, but no X-ray examination was performed. RESULTS: An
      average of 241 children per month were presented at the Children Emergency Unit
      after head trauma. An average of twenty-one X-ray examinations per month were
      performed instead of 194/month before february 1994. This represented a decrease
      of 2000 X-ray examinations per year. There was no undiagnosed neurological
      complication, and the number of children staying in the hospital for clinical
      supervision did not increase. DISCUSSION: Skull radiographies only show fractures
      and do not afford visibility of either brain or blood to demonstrate an
      intracranial injury. The presence of a skull fracture without neurological
      abnormalities is of little significance. Harwood-Nash reported that 60 per cent
      of the children with extradural hematoma, 85 per cent of the children with
      subdural hematoma and 35 per cent of the children with brain damage did not have
      any associated skull fracture. Clinical examination is essential, and it would be
      a mistake to be reassured about the severity of a head trauma because skull X
      rays are normal. CONCLUSION: Routine skull X-rays after head trauma are not
      justified either for financial or radioprotection reasons. In this study, more
      than half of the children were less than five years old and ran a higher risk of
      irradiation.

PMID- 9005458
TI  - [Low grade intramedullary osteosarcoma. Apropos of 8 cases].
AB  - PURPOSE OF THE STUDY: The authors reviewed eight patients treated for Low Grade
      Intramedullary Osteosarcoma (LGIO). They analyzed the radiographical and
      histological features and evaluated the prognosis of this disease. MATERIALS:
      Eight cases of LGIO were studied. The mean follow-up period was 3.9 years. LGIO
      is defined as a Broders classification grade I osteosarcoma. The study involved 3
      males and 5 females. Mean age at the time of diagnosis was 28. METHODS: Clinical
      records, radiographs and C.T. Scan were available and reviewed in all cases. Five
      patients had had MRI. In addition to the conventional histological study,
      ultrastructural studies were conducted in three of the cases. On their last
      examination, all patients received a clinical and X-ray assessment. RESULTS: The
      tumor was localized around the knee in six cases on the humerus and on the
      proximal femur in one case. The tumor was situated in the metaphysis and was most
      often lytic. A malignant tumor was suspected at the outset for only two of the
      patients. The scanner and the MRI revealed a cortical discontinuity and
      extraosseous involvement in five cases. Seven patients had a wide resection,
      which was intra-tumoral once. The histological examination of two of those
      resections revealed limited areas of anaplasia; complementary chemotherapy was
      then conducted. We did not observe any local recurrence in this group. We
      observed, however, an iliac metastasis, for which another wide resection was
      performed. This last patient remained free of disease three years later. One
      patient had radiotherapy and chemotherapy; he died from pulmonary metastasis
      after his LGIO turned into high grade osteosarcoma. DISCUSSION: LGIO are rare,
      they represent 1.8 per cent of all Osteosarcomas in the Cochin file. The mean age
      of patients contracting LGIO is higher than that of conventional osteosarcoma
      patients. Observation of the radiographs and histological examination could lead
      to think the tumor is benign, and mistake it with a fibrous displasia. The C.T.
      Scan and the MRI have the advantage of showing soft tissue invasion and help the
      histological examination. The wide resection is the only treatment able to cure
      the patient. Chemotherapy would be useful for LGIO cases containing limited arcas
      of anaplasia. CONCLUSION: LGIO is a slowly-evolving tumor. It remains localized
      for a long period of time. The histological diagnosis is difficult and requires a
      pathologist familiar with bone tumors. Its treatment requires surgery. LGIO must
      be distinguished from conventional osteosarcomas because of its better prognosis.

PMID- 9005459
TI  - [Synovial chondromatosis and chondrosarcoma. A study of the relationship between
      these two diseases].
AB  - PURPOSE OF THE STUDY: This retrospective study concerns six patients in whom
      chondrosarcoma was suspected to develop in synovial chondromatosis. We discuss
      for these cases different diagnosis. The authors expose the clinical signs and
      radiological aspects which suggest malignant transformation. We report the
      indispensable criteria for established diagnosis of malignant transformation of
      synovial chondromatosis and appropriated forms of therapeutic management were
      suggested. MATERIALS AND METHODS: Six patients, 3 males and 3 females from 36 to
      58 years of age were included in this study. Three patients presented 6 months, 3
      years and 25 years history of synovial chondromatosis of the knee joint. When the
      malignant transformation appeared, a surgical biopsy was performed and the
      pathologist diagnosed a chondrosarcoma in all cases. For the other three
      patients, the chondrosarcoma and synovial chondromatosis were diagnosed at the
      same time. The localization was shoulder, hip and knee. A surgical biopsy was
      performed and the pathologist diagnosed chondrosarcoma. Synovial chondromatosis
      was diagnosed by histologic examination of the resection or amputation specimen.
      TREATMENT AND RESULTS: Four patients had thigh amputation, one patient had "en
      bloc resection" of the hip-joint and the last patient had resection of the
      shoulder joint. In all cases, the histologic examination diagnosed chondrosarcoma
      and synovial chondromatosis. All patients were free of disease. DISCUSSION: The
      malignant transformation of synovial chondromatosis is rare but this diagnosis
      must be established to perform appropriate treatment. Other possible diagnosis
      are: low grade synovial chondrosarcoma initially diagnosed as a synovial
      chondromatosis. Bertoni believes that all cases of malignant transformation of
      synovial chondromatosis are initially low grade chondrosarcoma. We believe that
      his criteria are too strict for diagnosed chondrosarcoma. coexistence of synovial
      chondromatosis and synovial chondrosarcoma. These 2 diagnosis are extremely rare
      and their coexistence are unlikely. secondary synovial chondromatosis developed
      into chondrosarcoma. We don't have histologic criteria to confirm this diagnosis
      in all our cases. The symptoms that should suggest a malignant transformation of
      synovial chondromatosis were: rapid late deterioration of clinical conditions,
      bone invasion diagnosed by X-ray films and medullar invasion discovered by MRI.
      According to us, the indispensable criteria to diagnose malignant transformation
      were: 1.) histologic diagnosis of synovial chondromatosis established before
      diagnosis of chondrosarcoma, 2.) histologic diagnosis of chondrosarcoma on the
      same anatomic site as the synovial chondromatosis, 3.) diagnosis of
      chondrosarcoma and synovial chondromatosis on the same resection specimen. Only
      the three first cases were in accordance with these criteria. The treatment must
      be a "en bloc resection" of the joint or an amputation. CONCLUSION: Malignant
      transformation is rare, but this diagnosis should be established to perform
      adequate treatment. This diagnosis should be suspected when a rapid deterioration
      of the clinical status appeared and when bone involvement was detected by MRI.
      However, the danger still lies in the misinterpretation of the synovial
      chondromatosis as chondrosarcoma. This diagnosis can be made with clinical,
      radiological and pathological criteria. The treatment must be a wide resection or
      an amputation.

PMID- 9005460
TI  - [Treatment of femoral fractures on a total hip prosthesis using Charnley's "long
      stem" prosthesis. Apropos of 18 cases].
AB  - PURPOSE OF THE STUDY: This study was performed to analyse the clinical and
      radiological results obtained after the treatment of femoral fractures after
      total hip arthroplasties by a Charnley's extra long-stem prosthesis, and to
      compare these results with those obtained by alternative treatments proposed by
      various authors. MATERIALS: 18 patients, whose mean age was 68.5 years (extremes:
      45 to 86 years). Cooke and Newman fractures classification showed a clear
      prominence of type III. In 8 cases we found a femoral loosening, prior to the
      fracture, divided as follows: 4 in grade III and 4 in grade IV, using Vives
      classification. Type I fractures were always associated to complete femoral
      loosening. METHOD: Clinical results were analysed by Merle d'Aubigne's scoring
      system, giving a pre-fracture global score of 13.5. Post-operative radiological
      analysis was made on the appearance of femoral radiolucent lines and/or
      modification of the femoral implant. RESULTS: 17 patients were followed, with a
      mean of 5 years (extremes: 1 to 14 years). Consolidation was always obtained. The
      global mean functional results were of 15.2, with score improvement, essentially,
      of soreness and stability. We found 12 good and very good results, 4 poor and 1
      bad. Age (< 75 years) and fracture type (II and III) appeared to be important
      factors influencing the functional result, contrary to the lesional mechanism. 6
      non-evolutive bone-cement radiolucent lines appeared, in immediate post-operative
      phase. One cement-prosthesis radiolucent line appeared later, leading to
      loosening and rupture of the implant. We deplore 3 stem twistings, of which only
      one led to implant rupture. Walking with support was possible at the 5th
      postoperative days. DISCUSSION: Our functional results are encouraging (12 good
      results, i.e. 71 per cent), compared with other treatments. This technique
      improved the global functional score. This is due to the simultaneous treatment
      of the fracture and of the eventual pre-traumatic associated femoral loosening.
      The technique allows a quick resumption of autonomy, a short hospitalization time
      for these elderly patients. The main disadvantage of the orthopaedic treatment is
      the prolonged decubitus and the important risk of secondary loosening.
      Osteosynthesis by plate has the advantage of keeping a maximum of osseous stock,
      but delays weight bearing, favours the non union by a large loss of periosteum.
      It never permits the treatment of the associated loosening during the same
      operation. It is also at the origin of a cement weakening, while fixing the
      proximal screws, leading to the difficulty of placing the prosthesis. Major
      disadvantage of proposed method is the use of a high quantity of cement to ensure
      stability of the implants; but this has never had negative consequences in our
      study. CONCLUSION: This surgical technique seems to be a satisfying alternative
      to the treatment of femoral fractures on total hip arthroplasty, due to the
      advantages obtained. It is reserved for elderly patients. However, these findings
      should be taken with caution, due to our small series.

PMID- 9005462
TI  - [A 20-year follow-up study of internal gonarthrosis after tibial valgus
      osteotomy. Single versus repeated osteotomy].
AB  - PURPOSE OF THE STUDY: The study defines the conditions in which valgus osteotomy
      can produce satisfactory 20-year results in cases of medial unicompartmental
      gonarthrosis. MATERIAL AND METHODS: Among a series of 93 osteotomies, 35 knees
      were followed up for 20 years. Changes to the medial and lateral femorotibial
      compartments were identified on forced varus and valgus radiographs and on foot
      standing Xray. The condition of the patellofemoral articulation was defined on
      patellofemoral aspect at 30 degrees flexion. Frontal axial deviation was
      monitored by preoperative and postoperative standing film (first year, 10 years
      and 20 years). RESULTS: Only 25 knees still had a satisfactory functional result
      (no mechanical pain). However, among these 25 knees, 13 good functional results
      were obtained after a new osteotomy performed between the 7th and 15th year after
      initial surgery. There were therefore only 12 knees which managed to reach 20
      years with their original tibial osteotomy. Radiologically, in absence of adverse
      hypercorrection (greater than 6 degrees valgus), there was no deterioration or
      only small deterioration of the lateral femorotibial compartment at 20 years even
      among the knees which had undergone two tibial osteotomies. DISCUSSION: Osteotomy
      rarely avoids the problem of recurrent deformity which appears fairly rapidly
      (before 10 years) when initial correction is poor (below 3 degrees valgus).
      However, even correction of between 3 and 6 degrees valgus was not immune to
      recurrent varus deformity at long term (20 years): among knees with goniometry
      between 3 degrees and 6 degrees at the one-year postoperative review, 20 were
      still within this group by the 10th year; but only 9 knees were still in this
      range at 20 years. CONCLUSION: Whilst longevity of a tibial osteotomy seems
      limited, a second valgus tibial osteotomy can reproduce the same effects as the
      first (no pain and preservation of the medial femorotibial compartment): 13
      repeated tibial osteotomies produced a good result at 20 years follow-up which
      suggests that medial femorotibial gonarthroses in younger patients can be treated
      conservatively.

PMID- 9005461
TI  - [Coral as support of traumatic articular compression. A prospective study of 23
      cases involving the lower limb].
AB  - INTRODUCTION: Infection risk makes the management of a bone bank more and more
      difficult. On the other hand, realizing an autologous graft is not always without
      consequences. That is why we estimated the mechanical quality, the osteo
      integration and the biocompatability of a coral graft. MATERIAL AND METHODS:
      Between 1988 and 1992, two of us systematically used coral graft as "support"
      after lifting of some articular depression in fractures of inferior limb.
      Osteosynthesis was systematically associated. In this way, we operated 13
      fractures of the lateral tibial plateau, 8 thalamic fractures of the calcaneus
      and 2 fractures of the inferior extremity of the tibia. Average follow-up is 20
      months, with extremes of 68 and 12 months. Material ablation was realized 13
      times and coral graft biopsy 4 times. Bone integration was estimated
      radiologically in 3 stages: stage 1: non union = "margin" around the coral, stage
      2: possible integration = the coral is perfectly visible, but its borders grow
      indistinct, stage 3: certain integration = peripheral disparition of the coral
      weft, radiological interpenetration between coral and bone framework. We
      systematically searched for secondary displacements and complications. RESULTS:
      Mechanical conditions were respected, there was no secondary displacement.
      "Possible integration" (stage 2) was found in 8 cases at an average follow-up of
      20 months. In 9 cases, we found "certain integration" (stage 3), at an average
      follow-up of 28 months. It is possible that a more important follow-up time would
      allow to find more integration cases. Biocompatibility is debatable under the
      operating conditions of the authors. We counted 5 aseptic serous flows which
      continued to be aseptic (1 tibial plateau, 1 inferior extremity of the tibia, 3
      calcaneum). Three coral grafts were removed to obtain healing. DISCUSSION: When
      biocompatibility is satisfactory the integration is certain. The longer the
      follow-up time, the more stage 3 cases can be observed. Nevertheless, this
      integration runs out with time. We did not find any explication to aseptic serous
      flows. It may result from some impurities. On the other hand, use of the coralin
      hydroxyapatite does not seem to drive to allergic complications. CONCLUSION: In
      accordance with this study, we use the coral graft only in case of tibial plateau
      fracture. Our experience with coral graft in the other fields of bone surgery is
      not sufficient to express an opinion.

PMID- 9005463
TI  - [Percutaneous drainage of septic hip arthritis in children].
AB  - INTRODUCTION: Hip arthritis is a therapeutic emergency which requires sure
      diagnosis and pus evacuation. Two methods are presently in use: isolated or
      oriterative punction and arthrotomy. TECHNIQUE: A Pleurocath is introduced under
      general anesthesia and under fluoroscopic control by an obturator approach. It
      contains a perforated trocart which allows a flexible catheter, perforated over
      the last few centimeters to be inserted. The introduction point must be as far
      posterior as possible, in the plane of the anterior border of the femoral neck to
      promote declivious downward. It allows for pus evacuation, confirmation of the
      diagnosis and bacteriological samples to be taken. The lavage is done using
      ionized polyvidone dilution in physiological saline solution. The catheter is
      inserted in the center of the trocart and pushed intra-articularly under
      fluoroscopic control. The trocart is pulled out. The catheter is fixed on the
      skin using non resorbable thread. An occlusive dressing is made. A three way cock
      is installed for aspiration and lavage. Drainage is declivious. MATERIAL AND
      METHODS: This percutaneous drainage technique was used in three cases of septic
      hip arthritis in children. Treatment associated drainage, immobilization by
      traction and double or triple intravenous antibiotics. The hips healed without
      any detrimental effects. DISCUSSION: The punction had both a diagnosis and a
      therapeutic objective, as it allows pus evacuation in the same time. It can be
      repeated according to the patient's progress. Most authors prefer arthrotomy with
      careful lavage and good drainage. We suggest an intermediate technique which
      includes punction and allows clinical and bacteriological diagnosis, joint lavage
      and drainage. Using permanent drainage, the hip joint is protected from high
      pressure. It makes repeated lavage possible when the pus is thick, and avoids the
      drain from becoming plugged. CONCLUSION: This approach enables the pus to be
      evacuated, bacteriological samples to be taken, lavage and drainage. The drainage
      must be left until apyrexia and normal biological inflammation criteria are
      obtained.

PMID- 9005464
TI  - [Traumatic isolated palmar dislocation of the distal radio-ulnar joint. Apropos
      of a case].
AB  - PURPOSE OF THE STUDY: The authors report a rare case of an isolated palmar
      dislocation of the distal radio-ulnar joint (DRU). Diagnosis was easily
      established in emergency even though this lesion is usually unknown in 50 per
      cent of cases, according to literature. CASE REPORT: A surgical approach was
      necessary because of irreducibility of the lesion: ulna and radius were hitched
      with no other anatomical interposition. Treatment succeeded and the functional
      result was good with only 25 degrees of loss of pronation. This suggests a
      commentary on DRU joint physiology, on the mechanism of dislocation, and on the
      methods of treatment.

PMID- 9005465
TI  - [Isolated tuberculosis of popliteal cyst. Apropos of a case].
AB  - INTRODUCTION: Isolated localization of tuberculosis in the popliteal cyst is an
      exceptional affection. CASE REPORT: Mr. M.L., 18-year-old black moroccan, was
      admitted for a painful swelling of the left popliteal cyst, general state
      alteration and left thoracic pain. Clinical examination found a 5 cm on 3 cm oval
      tumefaction at the supero-medial part of the left popliteal hollow. No articular
      effusion was noted. Left knee X ray was normal, while ultrasound examination
      showed a modified popliteal cyst. Chest X ray showed a pleural effusion.
      Tuberculine skin test was positive (18 mm). A subtotal resection of the cyst was
      performed, evacuating 10 ml of thick pus. The histologic examination of the cyst
      confirmed its tuberculosis origin. In addition the left pleural biopsy confirmed
      the diagnosis of tuberculosis as well. The antibacillar treatment based on
      rifampicine, INH and pyrazinamide was given during 6 months. The evolution was
      favorable at 2 years of follow-up. DISCUSSION: Knee popliteal cyst is frequently
      an expression of an inflammatory or traumatic affection. The communication
      between the articular synovium and the serosa bursa of the lateral gastrocnemius
      is found in 50 per cent of cases, allowing an association of both localizations
      of tuberculosis. Hamabuchi described for the first time an isolated popliteal
      cyst tuberculosis in 1990. This case is similar to Hamabuchi's observation.
      Clinical and radiographical examinations were normal thus excluding a possible
      dissemination from the knee joint.

PMID- 9005466
TI  - [Deep muscular lipoma of the shoulder. Apropos of 4 cases].
AB  - PURPOSE OF THE STUDY: The authors report 4 cases of inter and intra-muscular
      lipoma of the shoulder and make a review of the diagnosis of this localization.
      MATERIAL AND METHODS: All 4 cases had shoulder pain and some limitation of
      shoulder motion, one had hypoesthesia on the lateral side of the arm. 3 had
      magnetic resonance imaging (MRI) and two ultrasonography examination, three of
      them had a surgical resection and for one surgery was considered too aggressive
      and had a MRI control one year later. RESULTS: There was no problem for the
      surgical procedure and the histology confirmed the diagnosis. The last patient
      had a rehabilitation program and the MRI control showed lesion stability.
      DISCUSSION: Lipoma are rare, X-rays, ultra-sonography and CT scans are not
      sufficient, MRI is the best exploration to differentiate lipoma and lipo-sarcoma,
      but the main problem is for low grade sarcoma. Histology is the only way to make
      the diagnosis with the whole tumor.

PMID- 9005467
TI  - [Treatment of chronic hepatitis C. Many interrogatives and some answers].

PMID- 9005468
TI  - [Pseudomonas aeruginosa: dreadful also in the AIDS patient editorial)].

PMID- 9005469
TI  - [Prevalence of the genotypes of the hepatitis C virus in Spanish drug addicts
      with chronic hepatitis C. Spanish Group for the Study of Viral Hepatitis in HIV
      Positive Patients].
AB  - The hepatitis C virus (HCV) shows a wide genetic variability. The different
      variants of HCV have been classified into 9 types and different subtypes. Some
      genotypes have a characteristic geographic distribution and seem to be associated
      with precise ways of contagion. Serum samples from 107 spanish patients with
      chronic hepatitis C were studied, which were distributed as follows: 88
      parenteral drug addicts (PDA) and a control group of 19 subjects made up by 4
      transfused, 5 probably sexually infected and 10 with unknown contagion source
      (sporadic cases). HCV typing was made by means of the PCR method and later
      hybridization analysis with complementary probes of different types and subtypes
      of HCV exposed on a smooth surface (Inno-LiPA). A total to 105 (98.4%) patients
      had their viruses genotypes. There was more than one genotype in the same subject
      (co-infection) in 43.8% of cases and co-infection 1a + 1b was the most common
      (82.7%). While not reaching a statistic significance, co-infections were more
      frequent in PDA (47.1%) than in the remaining patients (27.8%). In the infected
      patients with only one genotype, the most common genotype was 1a, both in PDA
      (22.9%) and in subjects with transfusional HCV, sexual or sporadic (38.9%). In
      decreasing frequency came genotypes 1b (13.3%) and 3a (11.4%). Other genotypes
      were very uncommon (2a and 4) or were absent (2b and 5) as unique infections. In
      conclusion, genotypes non-1b of HCV, mainly 1a and to a lesser extent 3a, are the
      most common in a spanish population made up mainly by young persons with risk
      antecedents for HIV infection, particularly PDA. Furthermore, co-infection with
      HCV genotypes is frequent in this population.

PMID- 9005470
TI  - [Respiratory infection caused by Pseudomonas aeruginosa in patients with HIV
      infection].
AB  - OBJECTIVE: Descriptive study of severe respiratory infections caused by
      Pseudomonas aeruginosa in patients with HIV infection. METHODS: Review of
      clinical records of HIV-positive patients admitted in a tertiary hospital from 1
      1-1990 to 9-30-1995. The patients included in this study were those with P.
      aeruginosa recovered from respiratory or blood samples and respiratory symptoms.
      RESULTS: Forty patients suffered 77 episodes. The incidence in the HIV-positive
      admitted population during the study period was 2.6% but 3.2% in the last year.
      Ninety-seven percent of patients met criteria for AIDS. Twenty-eight patients
      (70%) had other bacterial infections. In 78% of patients no classical
      predisposing factor was found for this infection. Twenty-seven patients (67.5%)
      came regularly to the day hospital or had been previously admitted to the
      hospital (recent hospitalization). Twenty-five episodes (32.5%) were tracheo
      bronchitis and 50 pneumonias (65%), of which 14 (28%) were cavitated and 7 (14%)
      bacteremic. Forty-nine percent of episodes were recurrences. Ten out of 15
      tracheo-bronchitis in the first episode recurred; the new episode was more severe
      in 7 patients. Five patients received secondary prophylaxis after the second
      episode (4 with tobramycin in aerosol and 1 with colistin in aerosol). Two
      patients had recurrences after 86 and 62 days (mean: 74; SD: 12). Eight out of
      the 11 patients who did not receive prophylaxis (73%) had recurrence after a mean
      of 23 days (SD: 10) (p = 0.002). The mortality rate associated with P. aeruginosa
      was 22.5%. CONCLUSIONS: The incidence of P. aeruginosa infections in our HIV
      positive patients was 2.6% (3.2% in the last year). It is associated with severe
      immunosuppression and previous bacterial infection. The subacute involvement of
      the lower respiratory tract is most common. Over 50% of infections tend to recur
      more severely. The secondary prophylaxis increased the symptom-free period,
      although the number of patients who received it was small.

PMID- 9005471
TI  - [Pseudomonas aeruginosa bacteremia in patients with HIV infection:
      clinicoepidemiologic study of 17 episodes].
AB  - BACKGROUND: Bacteremic infection with Pseudomonas aeruginosa is an uncommon and
      late phenomenon in the natural history of infection with human immunodeficiency
      virus (HIV). Our objective was to study the clinico-epidemiological
      characteristics of P. aeruginosa bacteremia (PAB) in patients infected with HIV.
      PATIENTS AND METHODS: A retrospective study of 17 episodes of PAB in 16 patients
      infected with HIV in three tertiary hospitals in the Valencia Community. Data
      were collected by means of a protocol designed to obtain clinical and
      epidemiological information. RESULTS: Fourteen out of 16 HIV-positive patients
      with PAB were males and in nine patients the risk factor for the acquisition of
      HIV was parenteral drug abuse. Eighty-one percent (13 patients) met diagnostic
      criteria for AIDS. Fourteen patients had less than 100 CD4 lymphocytes/mm3 at
      diagnosis of bacteremia (mean value 25.8). PAB was acquired in the community in
      13 episodes (76.4%). Nine patients (56.2%) had received some type of
      antimicrobial therapy during the last month, 12 (75%) were taking anti-retroviral
      therapy, and 6 (37.5%) were receiving prophylaxis against P. carinii. The most
      frequent source for PAB was pneumonia with 7 episodes (41.2%), followed by the
      intravascular catheter infection with 2 (12%). In six episodes (35.3%) no source
      was identified. Only one episode was evaluated as recurrence. Only two of the
      seven patients with pneumonia had pulmonary cavitation in the chest X-ray.
      Fifteen episodes resolved (94%) and in only one case was dead directly related to
      PAB. CONCLUSIONS: In our experience, PAB in patients infected with HIV emerges in
      the advanced stages of disease. The most common source was the lower respiratory
      tract and in most cases PAB was acquired in the community. The mortality rate
      resulting from PAB was lower than that previously reported in the literature.

PMID- 9005472
TI  - [The spectrum of bronchopulmonary infection caused by Pseudomonas aeruginosa in
      patients infected with the human immunodeficiency virus].
AB  - OBJECTIVE: To describe the clinical spectrum of bronchopulmonary infections
      caused by Pseudomonas aeruginosa in patients infected with HIV. METHODS: A
      retrospective study of cases with P. aeruginosa pneumonia and tracheo-bronchitis
      in patients infected with HIV, diagnosed over a 5-year period (January 1990
      December 1994) in a third level university hospital. RESULTS: Seven patients with
      pneumonia and 15 with tracheobronchitis were identified, with a mean age of 33
      years. All patients were in an advanced stage of immunosuppression (median CD4
      count 11/mm3) and 21 (95%) had AIDS. In 6 cases (86%) pneumonia was acquired in
      the community and no patient had severe neutropenia. Clinical presentation ranged
      from severe pneumonia with respiratory insufficiency and shock to subacute less
      severe disease. Two patients (29%) died in the first episode as a result of
      pneumonia. The combination of cough, purulent expectoration and fever was the
      usual presenting form of tracheo-bronchitis. Nine out of the 15 patients (60%)
      had been treated previously because of tracheo-bronchitis and/or bacterial
      pneumonia episodes not caused by P. aeruginosa. Twelve patients required hospital
      admission; ten patients (83%) because of tracheo-bronchitis symptoms. The initial
      response to therapy was satisfactory, but 12 (80%) relapsed, with 2.6 relapses
      per patient after a mean follow-up of 7.4 months. CONCLUSIONS: P. aeruginosa
      bronchopulmonary infections emerge in late stages of HIV disease. P. aeruginosa
      should be considered in the differential diagnosis of every patient with
      pneumonia and advanced AIDS, even in the absence of the traditionally reported
      risk factors. Initially, tracheo-bronchitis responds well to therapy, but its
      management is difficult because of the frequent relapses and the development of
      antibiotic resistance.

PMID- 9005473
TI  - [Bacteremia caused by Pseudomonas aeruginosa in patients with AIDS].
AB  - Severe infections caused by Pseudomonas aeruginosa are uncommon in patients
      infected with HIV. These infections are usually recurrent, bear a poor prognosis
      and their potential for nosocomial transmission is questioned. From May 1991 to
      December 1994, a total of 2,739 admissions were recorded at the VIH Unit in our
      hospital. Seven of those patients suffered 9 episodes of P. aeruginosa bacteremia
      (3.28 episodes/1,000 admissions). All cases were acquired nosocomially. The mean
      CD4 count was 30.7 cells/ml. Mortality associated with Pseudomonas aeruginosa
      bacteremia was 43%. With molecular typing techniques homologies over 98% were
      demonstrated for the two episodes in patient 4 and the episode in patient 3 (very
      close in time, 1993) and almost 99% between the isolate from patient 7 and the
      two isolates (identical) from patient 6. The other three isolates had
      relationship (to themselves and to the other isolates) lower than 97%. Our
      findings suggest that patient-to-patient transmission of severe infections caused
      by P. aeruginosa in patients with AIDS.

PMID- 9005474
TI  - [Analysis of interval cancers in the Program of Early Diagnosis of Cancer of the
      Breast of the Community of Valencia. Group of Readers of the Prevention Units of
      Cancer of the Breast].
AB  - A retrospective search was performed of interval cancers in the Programa de
      Prevencion de Cancer de Mama de la Comunidad Valenciana. The cancer rate observed
      was 0.5 per 1,000 women studied. The mean diagnostic time from the first
      mammography was 11 months, and the most frequent detection means was a positive
      palpation. The frequency was higher in women aged less than 55 years. More "non
      common" histologic types were found and a lower percentage of conservative
      therapies regarding cancers detected at the first round of the Program, although
      the stage was similar to the latter.

PMID- 9005475
TI  - [Necrotizing histiocytic lymphadenitis (Kikuchi-Fujimoto disease): contribution
      of 2 cases].
AB  - The necrotizing lymphadenitis of Kikuchi-Fujimoto is an uncommon disease in
      Spain. In a review of the literature we found only five cases reported until
      1995. We report here two patients with the diagnosis of this entity in an area
      hospital during a one-year period. This fact contrasts with the low frequency of
      this disease reported so far in our country. The cases were two young women who
      were investigated because of cervical lymph node enlargement and headache. The
      lymph node biopsy revealed typical findings of the necrotic phase of the Kikuchi
      Fujimoto disease in one case; the histology in the other case was characteristic
      of the so called proliferative phase. The two patients evolved spontaneously with
      a favorable outcome. Lymph node enlargements resolved in less than three months.
      All microbiological investigations performed were negative. One of the two
      patients was receiving intranasal calcitonin when symptoms developed. The
      incidence of Kikuchi-Fujimoto disease might be higher than considered. The
      spontaneous resolution of the disease and the requirement of the histological
      examination for its diagnosis are factors limiting its identification.

PMID- 9005477
TI  - [Vasculitis associated with HIV infection].

PMID- 9005476
TI  - [Lipoatrophic diabetes: review of the literature].

PMID- 9005478
TI  - [Slow-resolving pneumonia in an 86-year-old man].

PMID- 9005479
TI  - [A young woman with right hemiparesia, diplopia and familial antecedents of
      neurologic disease].

PMID- 9005480
TI  - [Differential diagnosis of Gitelman's syndrome and Bartter's syndrome, apropos of
      a case of metabolic alkalosis].

PMID- 9005481
TI  - [Hepatitis C virus infection in a patient with porphyria cutanea tarda and
      hepatocarcinoma].

PMID- 9005482
TI  - [hypouricemia caused by xanthinuria].

PMID- 9005484
TI  - [Usefulness of the bone marrow examination in HIV infected patients].

PMID- 9005483
TI  - [Treatment with interferon alpha of hemophiliacs with chronic hepatitis C].

PMID- 9005485
TI  - [Current developments in biostatistics].
AB  - Recent developments in biostatistics in three key areas: survival analysis of
      censured data, generalised linear models for correlated data, Bayesian modelling
      of complex data, are presented. Particular emphasis is placed upon illustrating
      common trends in these areas, in particular advances in computer intensive
      methods, the development of unifying modelling structures and the increasing
      variety of complex biomedical problems which can be realistically analysed.

PMID- 9005486
TI  - [Analysis of the health care market: which role for health economics?].
AB  - Since the early 70s, economists have tried to analyse health insurance and health
      care markets. In so doing, they have brought out the special features of this
      field of application, which require substantial adaptation of the standard
      economic tool kit. In conjunction with the twentieth anniversary of the Revue
      d'Epidemiologie et de Sante Publique, it is timely to question the relevance of
      economics to health and health care, its strengths and weaknesses. Such will be
      the purpose of this presentation.

PMID- 9005487
TI  - [Current aspects of infectious diseases in industrialized countries: development
      or history?].
AB  - Man's conception of nature is a historically dated phenomenon. Thus the recent
      development of infectious diseases in industrialized countries could either be a
      real phenomenon or simply an artifact related to our current conception of
      medical progress and research. Is the return of infectious disease a natural
      process or has modern civilization been less prudent than its predecessors? What
      are the characteristic features of modern pathogenesis? Are these "changes" the
      result of some natural dynamics or an evolution in our means of investigation?
      Modern civilization has not invented technological deviation or diseases of
      civilization, phenomena well know in the past, but what is new is the fact that
      science today, with an ever growing amount of information on molecular
      epidemiology, is still raising questions about infection, recognized new
      unsuspected forms of the living world which do not fit into our well-knitted
      outline of infectious agents. We have applied our simplistic and mechanistic
      schemas designed for the timespan of human life to the evolutionary processes.
      The effects of evolution and history are thus combined today in a novel way
      composing a new future for infectious diseases. This new way of looking at
      infectious diseases is not totally natural nor totally historical. It is perhaps
      an epistemological revolution going on within epidemiology. The return of
      infections disease would appear to have a direct effect on magnifying the
      knowledge and the delinquency of our culture.

PMID- 9005488
TI  - [Genetic epidemiology and frequent multifactorial diseases].
AB  - A global approach is required in the search for factors predisposing to
      multifactorial diseases. The analysis of genotypes must, of course, be integrated
      in addition to environmental factors and intermediary phenotypes as well as a
      precise evaluation of different clinical manifestations of the disease. A better
      understanding of the pathophysiological mechanisms involved is essential for
      intelligent selection of candidate genes, pertinent analysis of intermediary
      phenotypes and measurements of factors susceptible to influence the genetic
      effects. Strategy to identify factors of genetic susceptibility to frequent
      diseases does not necessarily involve linkage analysis.

PMID- 9005489
TI  - [20 years of cancer epidemiology. The clinician's viewpoint].
AB  - The future of cancer epidemiology remains wide open because of the slow progress
      in reducing mortality. Currently large scale screening is only conducted for
      cancer of the breast and cervix. Cancer of the colon is in the research stage.
      For all the other cancers, progress in prevention should result both from a
      better understanding of the causes and from more active participation by health
      care workers and the general population once risk factors have been clearly
      identified. Finally, it is important not to assess progress in therapeutics on
      the single criteria of long-term survival since one- or two- year remissions are
      important in terms of human life and may be the first signs of more durable
      progress in the future.

PMID- 9005490
TI  - [20 years of cancer epidemiology. The epidemiologist's viewpoint].
AB  - It is indeed a challenge to summarize in a few pages, 20 years of research in
      cancer epidemiology and the answer can only be very limited. Our understanding of
      risk factors has progressed both by a better evaluation of the importance of
      known factors and by the identification of new factors, in particular infectious
      and hormonal factors. Direct assessment of primary prevention activities has
      proved to be very difficult because more than 30 years may be required between a
      reduction in exposure to a carcinogenic substance and the observation of its
      consequences in terms of public health. The epidemiological knowledge of health
      care workers, media, decision markers and the general public has improved and all
      now know the main risk factors for cancer. However, the relative importance of
      these factors is poorly measured and unfounded fears about substances which are
      almost certainly not carcinogenic, are adding to the confusion.

PMID- 9005491
TI  - [20 years of cardiovascular epidemiology. The clinician's viewpoint].
AB  - Over the last twenty years, several important clinical trials have brought major
      advances in the field of prevention and treatment of cardiovascular diseases.
      Fibrinolytic drugs, ACE inhibitors, new antiplatelet drugs or new tools in the
      field of interventional cardiology have been studied and have changed the daily
      practice of the cardiologists. Several remarks and comments are proposed with
      regards of these trials.

PMID- 9005492
TI  - [20 years of cardiovascular epidemiology. The epidemiologist's viewpoint].
AB  - The author reviews the evolution of cardiovascular epidemiology during the twenty
      last years. The mortality from cardiovascular diseases with atherosclerosis as
      their pathological basis grew rapidly in the industrialised countries after World
      War II. This led to epidemiological research which started in 1950 with
      respectively the studies of Framingham in the United States and the Seven
      Countries Study, essentially in Europe. The concept of multifactorial origin of
      coronary heart disease was proposed during the 60s. Three major coronary risk
      factors besides age and gender, hypercholesterolemia, hypertension and cigarette
      smoking emerged systematically in epidemiological studies before 1975. The last
      twenty years have confirmed the importance of these three modifiable coronary
      risk factors which are long-term predictors in different ethnic groups, both in
      males and females. Other risk factors appeared in this period. Some polymorphisms
      of several genes as well as their phenotypic expression have been found to be
      related to an increased risk of coronary heart disease. Uni- and multifactorial
      primary and secondary prevention trials have confirmed the observations of
      analytical epidemiology. Moreover, the crucial role of nutrition within a
      metabolic hypothesis has been confirmed by experimental research. The concept of
      the strategy of prevention in higher risk subjects as well as in the whole
      population was proposed by international bodies following the publications by the
      English epidemiologist G. Rose. Both France and Belgium contributed to the
      development of cardiovascular epidemiology during the last twenty years. France
      is doing cutting-edge research on genetic predictors of cardiovascular diseases.
      Although the multifactorial causal model of cardiovascular diseases is robust, it
      is still a probabilistic one; it predicts however relative risks of about 15 to 1
      according to the decile of the multilogistic function distribution. Environmental
      factors essentially related to lifestyles explain a great part of these
      differences. At the individual level, genetic factors most probably modulate
      these environmental influences and one can foresee in the future a more
      predictive model. In most medical schools, teaching of cardiovascular
      epidemiology and prevention has a low priority with clinicians putting the accent
      on the risk factors rather than on the risk profile of the individual. Secondary
      prevention is more in the realm of clinical medicine due to a large publicity
      given to the results of the large randomised trials. Consequently, in hospital
      mortality of acute myocardial infarction is decreasing as well as long-term
      mortality. Finally, prevention at the population level is connected to political
      decisions in public health which could have a major impact on the economy at the
      country level. Consequently, these political decisions are very slow to be taken
      both at the national and European Union level.

PMID- 9005493
TI  - Twenty years of epidemiology in fertility regulation.
AB  - This paper summarizes findings from epidemiological research in fertility
      regulation which have helped in formulating policies nationally and
      internationally, without pretending to be all-encompassing; rather, it should
      help in demonstrating the usefulness and importance of epidemiological research
      and in discussing outstanding issues of public health relevance.

PMID- 9005494
TI  - [20 years of research in epidemiology of human reproduction].
AB  - During the last two centuries, humanity has gone through two major
      transitions:first a demographic transition and second an epidemiological
      transition. In this moving environment, attention has been placed on a better
      understanding of the conditions of human reproduction. The role of epidemiology,
      a quantitative discipline, situated at the interface between biology, medicine
      and social sciences, has largely contributed to favoring advances in knowledge
      and rational use of data, with the aim of improving the health of the general
      population. Inversely, the new problems involved in the complex situation of
      human reproduction, of which using two individuals as the basic statistical unit
      for procreation is not of the least importance, have certainly contributed to the
      advancement of epidemiology.

PMID- 9005495
TI  - [20 years of perinatal epidemiology. The clinician's viewpoint].
AB  - Three periods are described. The first is the period of perinatality from 1971 to
      1981 during which the precise objective was to reduce perinatal mortality and
      morbidity based on actions proposed after cost-effectiveness analysis and early
      surveys in France to evaluate the effect of these actions. This plan allowed a
      new policy including prevention of prematurity and improvement in delivery
      conditions. National surveys have shown a reduction in prematurity rates and
      perinatal mortality. The second period was a wait-and-see period with the abandon
      of national actions, but also a transfer of responsibility for perinatal health
      to the different departments. Certain departments developed perinatal
      actions:actions in Martinique and Guadeloupe are described together with the
      early audit on perinatal care in Seine-Saint-Denis. The third period, the current
      period, began in 1994 when the government proposed a new perinatality plan based
      on a new perception of maternal mortality risk and a come back of the idea of a
      collective approach to safe birth.

PMID- 9005497
TI  - [Neurotoxicity of 5% hyperbaric lidocaine in subarachnoid anesthesia?].

PMID- 9005496
TI  - [20 years of perinatal epidemiology. The epidemiologist's viewpoint].
AB  - On the methodological point of view, perinatal epidemiology has been
      characterized in these last twenty years, by the development of evaluative
      surveys and their integration into a set of epidemiological works allowing a
      better understanding of the underlying pathophysiological mechanisms providing a
      basis for preventive interventions.

PMID- 9005498
TI  - [Usefulness of the preoperative electrocardiogram in elective surgery].
AB  - OBJECTIVES: To assess the prevalence of abnormal electrocardiograms (ECG)
      recorded routinely in patients undergoing elective surgery as well as the
      prevalence of ECG abnormalities that could not be predicted by the patient's
      medical history. To determine the influence of ECG results on patient care. To
      identify patient groups at high risk for abnormal ECG. PATIENTS AND METHODS:
      Retrospective study of 2,146 patients scheduled for non cardio-thoracic surgery
      requiring anesthesia. Two physicians reviewed the preoperative ECG reports in
      consultation with a cardiologist. The reports were considered normal, abnormal
      but expected or abnormal and unexpected based on agreement or not with the
      patient's medical history. RESULTS: The 161 (7.4%) patients for whom data was
      missing were excluded. Preoperative ECGs were performed in 1,898 (95.6%) cases.
      Abnormal ECG results were reported for 351 (18.5%), most often for men, patients
      over 45 years of age, those classified ASA III-V, those with cardiovascular
      disease, kidney failure and diabetes mellitus. Two hundred seventy unexpected
      abnormalities were found in 234 (12.3%) patients. Of these, 117 (43.3%) were
      considered major. The unexpected abnormalities motivated changes of attitude
      toward 4 (1.7%) patients, but new treatment was established for only 2 (0.8%) of
      them. The prevalence of unexpected abnormalities was higher in men, patients over
      45 years of age and those classified as ASA III-V. CONCLUSIONS: The prevalence of
      unexpected preoperative ECG abnormalities among non cardio-thoracic surgical
      patients is high but the influence of such results is minimal. The sensitivity
      and specificity of preoperative ECG for detecting electrocardiographic
      abnormalities are low. We suggest that performance of ECG before surgery is
      useful in patients over 45 years of age or in those with cardiovascular disease,
      chronic kidney failure, diabetes mellitus, physical state ASA III-V and those for
      whom it has not been possible to obtain an adequate medical history or perform a
      complete physical.

PMID- 9005499
TI  - [Influence of cardiac or respiratory pathology in the gasometric evolution during
      laparoscopic cholecystectomy].
AB  - OBJECTIVES: To analyze the differences in gasometric behavior during laparoscopic
      cholecystectomy in patients with heart or respiratory disease. PATIENTS AND
      METHODS: Prospective study of 19 ASA III patients grouped according to whether
      they suffered heart (group H, n = 10) or respiratory (group R, n = 9) disease.
      The patients were ventilated without reabsorption of CO2 and a flow volume of 12
      ml/kg in order to achieve a positive end tidal pressure of CO2 (PetCO2) between
      25 and 30 mmHg and no subsequent changes in ventilatory parameters. Arterial and
      venous gasometric values, PetCO2, hemodynamic data and airway pressure were
      analyzed at the following times: T1, 15 min after induction; T2, 20 min after
      insufflation; and T3, 5 min after de-insufflation. RESULTS: PaO2 was
      significantly higher in group R than in group C (238 +/- 31 versus 196 +/- 32
      mmHg, respectively, p = 0.015). PaCO2 rose gradually in both groups and the
      increase was significant between T1 and T2 (group C: 30 +/- 4 to 34 +/- 3 mmHg, p
      = 0.008; group R: 31 +/- 6 to 35 +/- 5 mmHg, p = 0.032). PvCO2 rose significantly
      in group C (39 +/- 4 to 42 +/- 4 mmHg, p = 0.001). The arteriovenous differences
      in CO2 increased in group C between T2 and T3 (6 +/- 3 to 11 +/- 6 mmHg) but the
      difference was not significant. PetCO2 increased after pneumo-peritoneum in group
      C (26 +/- 3 to 30 +/- 4 mmHg, p = 0.003). The arterial-PetCO2 gradient did not
      change. CONCLUSIONS: Laparoscopic cholecystectomy is a safe technique for use in
      patients with cardio-respiratory risk factors, even though there is a gradual
      increase in PaCO2. Physiological changes were greater in the patients with heart
      disease.

PMID- 9005500
TI  - [Detection of microbubbles formed in the blood/CO2 interphase during
      decompression in barometric conditions similar to laparoscopy].
AB  - HYPOTHESIS AND OBJECTIVES: Intraperitoneal insufflation (IPI) with CO2 during
      laparoscopic surgery establishes a pressure gradient that determines the passage
      of gas from the peritoneal cavity to the blood and surrounding tissues. The
      transport and clearance of CO2 are assured by proper sweeping when regional blood
      flow is adequate in volume and distribution. But if IPI hyperpressure surpasses
      regional venous capillary pressure (10 to 15 mmHg) and there is no cardio
      circulatory adaptation to the phenomenon, CO2 clearance may be compromised. Under
      these conditions, the expected post-insufflation increase in PetCO2 will not take
      place. Bearing in mind the physical characteristics of CO2, retention of this gas
      in the intraperitoneal cavity produces blood and tissue saturation under a higher
      than-atmospheric pressure, after a certain period of time in contact. Rapid
      intraperitoneal decompression after laparoscopic surgery carries with it the risk
      of microbubble formation due to release of CO2 that had been dissolved under
      hyperbaric conditions. MATERIAL AND METHODS: To test this hypothesis, the
      barometric conditions of laparoscopy were reproduced inside an observation
      capsule containing blood and CO2. RESULTS: Magnification revealed that after
      decompression bubbles formed in the blood/CO2 interphase. The images were
      recorded on magnetic videotape. Thirty minutes after decompression, the bubbles
      could still be seen, even after the interphase was swept with a current of air.
      DISCUSSION: Rapid intraperitoneal decompression after laparoscopy can generate
      the formation of microbubbles which, if not eliminated, will give rise to local
      ischemic manifestations. This same decompression, correcting the local
      circulatory alterations and activating the CO2 transport that had been
      compromised, could introduce gas bubbles into the blood stream such as are
      responsible for delayed gaseous microembolism. The simultaneous observation of
      changes in PetCO2 (stability or post-insufflation decreases) and hemodynamic
      parameters during laparoscopy, would allow evolving anomalies to be detected
      early and therapeutic action to be taken to prevent the formation of
      microbubbles.

PMID- 9005501
TI  - [Efficacy of the ilioinguinal and iliohypogastric block in the treatment of the
      postoperative pain of inguinal herniorrhaphy].
AB  - INTRODUCTION: The ileoinguinal-ileohypogastric block (IHB) improves pain control
      in inguinal hernioplasty. OBJECTIVE: To determine the efficacy of the IHB on the
      treatment of postoperative pain in inguinal herniorrhaphy, and to compare the
      effect of its use before and after incision for diminishing pain and postponing
      the first dose of analgesia. PATIENTS AND METHODS: Sixty-eight patients scheduled
      for inguinal herniorrhaphy with mesh were enrolled and distributed randomly in 4
      groups as follows: 1) IHB before incision using 0.25 ml/kg bupivacaine 0.5% with
      no vasoconstrictor; 2) IHB after incision with the same dose of bupivacaine; 3)
      IHB before incision with 0.25 ml/kg of serum; and 4) IHB after incision with 0.25
      ml/kg of serum. Pain was evaluated on visual analog scales employing facial
      expressions and verbal description, a patient questionnaire and time elapsing
      between surgery and the first dose of analgesia. The evaluations were performed
      in the postoperative recovery unit and on the ward 8 and 24 hours after surgery.
      RESULTS: The total overall score for postoperative pain was lower in the
      bupivacaine group than in the placebo group (9.2 +/- 4.4 and 1.5 +/- 3.9,
      respectively; p = 0.026). The first dose of analgesia was given to those who
      received placebo between the second and third hour after surgery, whereas it was
      given between the fourth and fifth hour to the bupivacaine group. No significant
      differences were found between infiltration before and after incision.
      CONCLUSIONS: IHB decreases pain, delaying the need for a first dose of analgesic
      and improving patient comfort. Its use is therefore recommended for relief of
      postoperative pain.

PMID- 9005502
TI  - [Hyperbaric medicine and anesthesiology].

PMID- 9005503
TI  - [Chronic subdural hematoma secondary to an accidental dural puncture during
      lumbar epidural anesthesia].
AB  - We report the case of a 54-year-old woman with cephalea of five months duration
      caused by a chronic subdural hematoma that appeared after epidural anesthesia and
      accidental dural puncture for bilateral saphenectomy. Computed tomography of the
      brain revealed an intracranial hematoma. After surgical evacuation, the patient's
      headaches resolved and she recovered fully. The appearance of cephalea after
      dural puncture is a relatively frequent complication of spinal anesthesia, but
      its persistence over time, as well as changes in its initial characteristics,
      should lead to a suspicion of life-threatening subdural hematoma.

PMID- 9005504
TI  - [Pain in the lower extremities after subarachnoid block with lidocaine].
AB  - Subarachnoid block is a widely practiced anesthetic technique. With the
      availability of small-diameter needles and the rises in out-patient surgery, the
      number of procedures performed with subarachnoid block and short-term local
      anesthesia have increased. We report two cases of bilateral pain in the lower
      extremities appearing 20-24 h after intradural anesthesia with 2% hyperbaric
      lidocaine. We analyze the factors that might have triggered this complication and
      compare the two patients with 14 others described in the literature. Three points
      in common were found: the use of hyperbaric lidocaine, administration of the
      agent through small gauge needles and the performance of out-patient surgery.

PMID- 9005506
TI  - [Monitoring and pharmacologic treatment of a patient with primary pulmonary
      hypertension].

PMID- 9005505
TI  - [Anesthesia for the surgery of delayed postoperative stenosis in the pulmonary
      suture in children with corrected transposition of the great vessels with
      Jatene's technique].
AB  - Any patient with congenital heart disease is at high risk for anesthesia no
      matter what surgical procedure is performed. Children undergoing D-transposition
      of the great arteries using Jatene's technique present stenosis of the pulmonary
      artery in 10-20% of cases and may require surgery to correct that or some other
      surgically caused anomally. In either case the children must be managed as
      patients with heart disease, with special attention to cardiovascular depression
      and rhythm abnormalities. We report the cases of two children who underwent D
      transposition of the great arteries in the neonatal period using Jatene's
      anatomical technique. They were later anesthetized at ages 5 and 6 years to
      correct pulmonary suture stenosis. Recovery was good.

PMID- 9005507
TI  - [Factors causing cardiac herniation after thoracic surgery].

PMID- 9005508
TI  - [Cardiovascular collapse after cemented prosthesis: bone cement or a massive
      embolism?].

PMID- 9005509
TI  - [Tomas Alday and the chemical synthesis of somnifen].

PMID- 9005510
TI  - [Reconstructive surgery of rheumatic mitral valvulopathy in patients under 18
      years of age].
AB  - OBJECTIVE: To present our experience in 58 children (37 female, 21 male) aged 4
      to 18 years (mean +/- SD = 14.9 +/- 2.7) with rheumatic mitral valve disease who
      underwent surgical reconstruction. METHODS: They were divided in four groups
      according to the abnormalities of the mitral apparatus: Group I had mitral
      regurgitation due to lesions located in the valvar structures with normal valvar
      movement (n = 1, 2%), group II mitral regurgitation with lesions located mainly
      in subvalvular structures with valve prolapse (n = 11, 19%), group III with
      mitral regurgitation due to lesion located both in valvular and subvalvular
      structures and restricted valvar motion (n = 38, 65%), and group IV included
      patients with stenosis (n = 8, 14%). RESULTS: Surgical mortality was 5% (3/58)
      and three patients (5%) were reoperated immediately. The 52 remaining patients
      were followed from 6 to 108 months (mean 45.8 +/- 30.1 months, 199 patient
      years). Six cases were reoperated in the follow-up (3.0% per patient-year). The
      functional class using the criteria of the New York Heart Association was
      evaluated before and after the procedure: class I raised from two to 42 patients
      whereas it decreased in the others (class II from 13 to 7, class III from 38 to
      3, class IV from 5 to none; p < 0.001). The cardiothoracic index decreased from
      0.61 +/- 0.064 before surgery to 0.55 +/- 0.069 after surgery (p < 0.001). Thirty
      patients (57%) were evaluated with echo-Doppler in the follow-up period. There
      were no deaths in the follow-up period. CONCLUSIONS: Our data shows that
      reconstructive surgery of the mitral valve with rheumatic involvement offers good
      immediate and late results, with a low reoperation rate, avoiding the use of
      prosthetic valves as a first option.

PMID- 9005511
TI  - [Prevalence of silent myocardial ischemia in non-insulin dependent diabetes].
AB  - OBJECTIVE: To evaluate the prevalence of silent myocardial ischemia in patients
      with non-insulin dependent diabetes mellitus with no symptoms of cardiac disease.
      SETTING: Tertiary care center. PATIENTS: 60 patients with non-insulin dependent
      diabetes mellitus; mean age 58 +/- 12 years, who had no symptoms of angina or any
      other clinical evidence of coronary artery disease and normal resting
      electrocardiogram. A control group of 57 healthy volunteers, matched for age and
      sex were included. MEASUREMENTS: All patients underwent a 24 hour
      electrocardiographic Holter monitoring test. An ischemic episode was defined as
      depression of the ST segment > or = 1 mm for > or = 1 min. RESULTS: 10 of the 60
      diabetic (17%) were found to have silent myocardial ischemia and only 3/57 (5%)
      was detected in the controls. In a two years follow up, four diabetics developed
      symptomatic angina pectoris. CONCLUSIONS: Silent myocardial ischemia in
      asymptomatic diabetics occurs frequently; a lack of symptoms does not discard a
      myocardial ischemia, and the Holter recordings may help in its detection.

PMID- 9005512
TI  - [Detection of aneuploidies using in situ hybridization in cells of the oral
      mucosa].
AB  - Aneuploidies have been traditionally diagnosed by chromosome analysis, however
      this method may be difficult to perform in certain cellular types or in severely
      ill patients. With the fluorescence in situ hybridization (FISH) technique it is
      possible to identify the number of specific chromosomes in interphase cells. In
      the present study we analyzed exfoliated epithelial cells from the oral mucosa of
      15 patients with trisomy 21, and in six patients with mosaicism; five normal
      subjects were included for comparison. To allow the probe to reach its target DNA
      we first treated the keratin-surrounded membrane with pepsin during 20 minutes.
      In the 15 cases of trisomy 21, the cells showed five fluorescent signals
      indicating the presence of three chromosomes 21 and two 13, while the normal
      subjects showed four signals. In one girl with Turner syndrome and a karyotype
      46,X+mar, the FISH analysis in 1000 cells revealed that the marker derived from
      chromosome X and there was a mosaicism 45,X/46,X,r(X). In the other patients with
      mosaicisms, we observed variations in the proportions of cells but the
      differences were not significant. In conclusion, interphase FISH on buccal cells
      showed to be a rapid, effective and non-invasive method for the diagnosis of
      chromosome aberrations, particularly when the cytogenetic study on lymphocytes is
      difficult to perform.

PMID- 9005513
TI  - [Respect for the interests of pediatric patients].
AB  - Physicians face situations involving ethical values. In the absence of
      instruments for exploring ethical issues in pediatric practice we developed a
      questionnaire (PEIPP: acronym in Spanish of implicit ethical principles in
      pediatric practice) to identify whether pediatricians show respect to the
      attributions of patients. PEIPP was validated by iterative evaluation by experts:
      a Kuder Richardson's coefficient of 0.98 and a concordance mean index of 0.80
      were obtained. PEIPP included two kinds of vignettes: three vignettes exploring
      how physicians provide information to patients, and seven of how pediatricians
      make decisions in some specific circumstances. Five groups of pediatric residents
      (n = 53) and three groups of pediatricians (n = 76) in three hospitals
      participated. Globally there were no differences between residents and staff. In
      the vignettes exploring actions, there was a large variability in the answers
      whereas in the vignettes of information there was a general tendency to select
      the options indicating a respectful attitude. There was no correlation in the
      respectfulness between the two types of vignettes, nor between respectfulness and
      years of experience of the pediatricians. Less than 10% of residents and
      pediatricians showed a high consistency in answers indicating respectfulness. We
      conclude that a respectful attitude is not common in the group of physicians
      studied.

PMID- 9005515
TI  - [Reading ability of family physicians].
AB  - OBJECTIVES: To measure the abilities of comprehension and interpretation of
      medical texts by first-level physicians, and to explore their association with
      length of clinical experience. MATERIAL AND METHODS: An instrument of two texts
      (sociomedical and ethical areas) with 40 items related to comprehension and 40 to
      interpretation was used. Its construct and content were validated by 10 experts
      and achieved a consistency of 0.99 (Kuder-Richardson). It was used in 104
      physicians selected at random from the 408 working in eight first-level clinics
      of the Mexican social security system in Mexico City. The Mann-Whitney test was
      used to evaluate differences between two groups, and the Kruskal-Wallis test for
      more than two groups. RESULTS: Higher scores were seen for comprehension over
      interpretation globally (p < 0.0001) and when partitioned by postgraduate studies
      (higher if yes, p 0.01), years of experience (lower if > 20, p 0.02), and gender
      (higher in women, p 0.03), but no differences were seen by clinic. Differences in
      interpretation were not observed. CONCLUSIONS: Interpretation was less developed
      and did not change with experience. There appeared to be a problem of a
      deteriorating capacity of comprehension with experience.

PMID- 9005514
TI  - [Auditory evoked potentials in addicts to organic solvent inhalation].
AB  - Organic solvents affect the membrane lipids of neurons and glial cell. This led
      us to search for auditory damage, by means of brainstem auditory evoked
      responses, in subjects with chronic inhalation of thinner. Waves III and V showed
      delayed latency at an intensity of 90 dB, and wave V was delayed at 70 and 30 dB;
      the interwave intervals I-III and I-V at 90 dB and the interpeak I-V at 70 dB
      were also retarded. Three subjects did not show a response to stimulation at 30
      dB: pure tone audiometry showed biaural mild hypoacusia in them. These results
      show that chronic inhalation of thinner may alter the auditory pathway of
      addicts.

PMID- 9005516
TI  - [Lymphotropic viruses type I and II in pregnant women in Yucatan].
AB  - No antibodies against HTLV-I and HTLV-II were detected in 590 gestating women
      residing in the Yucatan peninsula sampled between Jan/92 and May/93.

PMID- 9005517
TI  - [Pharmacology and toxicology of Spirulina alga].
AB  - Spirulina, a unicellular filamentous blue-green alga has been consumed by man
      since ancient times in Mexico and central Africa. It is currently grown in many
      countries by synthetic methods. Initially the interest in Spirulina was on its
      nutritive value: it was found almost equal to other plant proteins. More
      recently, some preclinical testing suggests it has several therapeutic properties
      such as hypocholesterolemic, immunological, antiviral and antimutagenic. This has
      led to more detailed evaluations such as nucleic acid content and presence of
      toxic metals, biogenic toxins and organic chemicals: they have shown absence or
      presence at tolerable levels according to the recommendations of international
      regulatory agencies. In animal experiments for acute, subchronic and chronic
      toxicity, reproduction, mutagenicity, and teratogenicity the algae did not cause
      body or organ toxicity. In all instances, the Spirulina administered to the
      animals were at much higher amounts than those expected for human consumption. On
      the other hand there is scant information of the effects of the algae in humans.
      This area needs more research.

PMID- 9005518
TI  - [Molecular biology in medicine. V. Polymerase chain reaction].

PMID- 9005519
TI  - [Genital herpes].
AB  - Herpes is the first cause of genital ulcers, recurrences are unpredictable and
      asymptomatic viral excretion is frequent. Herpes simplex virus 2 is responsible
      for genital infection in 80% of cases, but the incidence of Herpes simplex virus
      1 is rising. New diagnostics methods are developing, batcellular viral culture
      remains gold standard. Oral aciclovir is the standard treatment, and directions
      for use are strictly codified. In pregnant women a new preventing project is
      proposed, it does not prevent transmission during asymptomatic viral excretion.
      In immunocompromise patients Herpes is frequent severe and sometimes aciclovir
      resistant.

PMID- 9005520
TI  - Mediators in acute pancreatitis. Proceedings of a meeting. Liverpool, United
      Kingdom, 23 June 1995.

PMID- 9005521
TI  - [The bane of giant cell arteritis from an ophthalmological viewpoint].
AB  - We report a series of 21 consecutive patients seen at the Ophthalmology
      Department of the University Hospital Zurich, Switzerland, with the arteritic
      form of anterior ischemic optic neuropathy (AION). 19 patients had giant cell
      arteritis, one had periarteritis nodosa and one had cP-arteritis. They comprised
      11 men and 10 women, ranging in age between 66 and 88 years. The median age was
      80. We analyzed the course of events in each case before and after involvement of
      the first eye, as well as the frequency and possible causes of involvement of the
      second eye. The diagnosis was regarded as delayed when, despite typical signs,
      symptoms amd laboratory abnormalities, systemic vasculitis was not considered in
      the differential diagnosis. Treatment was considered inadequate if, following
      visual loss in one eye and diagnosis of a systemic vasculitis, a dose of 1 mg/kg
      prednisone or less was given, and/or the initial dose was reduced by more than
      50% during the first month. Of 21 patients, 10 suffered bilateral visual loss. 8
      of these 10 patients became legally blind. In 13 out of 21 cases there was no
      delay in diagnosis and treatment was adequately given. All 11 patients with
      unilateral involvement, who did not suffer a substantial loss in quality of life,
      belong to this subgroup. In 8 cases diagnosis was either delayed or treatment was
      inadequate. All of these patients had bilateral ocular involvement. In one
      patient, visual loss in the second eye could not be avoided despite correct
      diagnosis and treatment (M.A., No. 1). In this patient the interval between
      involvement of the first and second eye was very short (3 days). One patient had
      a mature cataract in the first affected eye and sought medical help only after
      his good eye became involved (K. F., No. 15). In this report we would like to
      draw attention to the extremely poor visual prognosis due to frequent bilateral
      ocular involvement in giant cell arteritis. Corticosteroid treatment cannot
      restore vision in the already affected eye, but it is, in the majority of cases,
      highly effective in preventing visual loss in the second eye. Thus, it is crucial
      to begin treatment immediately, to start with a high dose (preferably 1 g methyl
      prednisolone i.v.), and to continue high-dose oral treatment long enough to
      prevent delayed visual loss in the second eye. The most vulnerable period appears
      to be the first month following involvement of the first eye. Caring for patients
      with giant cell arteritis who have lost vision in one eye is a challenge to all
      involved physicians. It resembles a "high-wire act" with the threat of blindness
      on the one hand and the dangers of long term corticosteroid treatment on the
      other. An interdisciplinary approach with ongoing communication between the
      family physician and the ophthalmologist is required.

PMID- 9005523
TI  - [Bernard-Soulier thrombocytopenia: clinical significance of a rare disorder].
AB  - We present 5 cases with thrombocytopenia and abnormal platelet function. The
      diagnosis of Bernard-Soulier syndrome was suspected in some subjects of advanced
      age on the ground of morphologic changes in the thrombocytes and of low platelet
      counts with or without prolonged bleeding time. The platelets showed normal
      aggregation with adrenalin, ADP and collagen but abnormal agglutination with
      ristocetine. All patients had normal von Willebrand factor levels in plasma. Flow
      cytometry demonstrated on thrombocytes lack of GP Ib expression of varying degree
      in comparison to normal controls, using various anti-GP Ib-antibodies (CD42b).
      The combination of these findings confirmed the diagnosis of Bernard-Soulier
      syndrome with varying expression of GP Ib. Flow cytometry and the use of specific
      monoclonal antibodies may be a rapid and reliable diagnostic tool. Differential
      diagnosis and treatment strategies are discussed. A congenital thrombopathy
      should always be considered in patients with thrombocytopenia of unknown origin
      and abnormal platelet morphology.

PMID- 9005522
TI  - [Clinical aspects and prognosis of candidemia, a 6-year retrospective study].
AB  - In recent decades an increase in the incidence of fungal infection has been
      reported. We retrospectively analyzed 41 patients with candidemia seen at Basel
      University Hospital over a six-year period. 1.2-6.7 candidemias per 10000
      admissions were observed. In contrast to other studies, there was no increase
      during the study period. Out of 41 patients, 19 were hospitalized in ICUs. All
      patients had risk factors such as intravascular catheters (92.7%), antibiotic
      therapy (88%), immunosuppressive therapy (31%), indwelling Foley catheters (54%)
      and previous surgery (63%). The most frequent symptoms were fever with rigor,
      tachycardia and hypotension. The isolates were Candida albicans (n = 28),
      Torulopsis glabrata (n = 5), C. krusei (n = 3), C. parapsilosis (n = 2), C.
      guilliermondii, C. kefyr and C. lusitaniae (n = 1 each). In 22 patients, candida
      colonization had been documented and 5 patients had superficial mucocutaneous
      candidiasis before candidemia. The initial foci were the gastrointestinal tract
      (n = 13), an intravascular catheter (n = 8), the urinary tract (n = 5), the
      respiratory tract, or intravenous drug use (n = 3 each). Out of 32 patients who
      were treated either with amphotericin B or fluconazole, 13 died. 5 of the
      untreated patients died, in 3 instances before microbiological diagnosis. The
      mortality was similar for treatment with amphotericin B and with fluconazole (50%
      vs. 33%) (p = 0.3).

PMID- 9005524
TI  - [Group A beta-hemolytic streptococcal meningitis in a pregnant woman].
AB  - A case of group A streptococcal meningitis in a normally healthy pregnant woman
      is described, with a review of the literature. Streptococcus pyogenes is a very
      rare cause of bacterial meningitis and especially affects immunocompetent
      subjects. The evolution is often associated with severe neurologic deficits, but
      the prognosis is favourable under treatment with penicillin. In the light of the
      recrudescence of invasive infections, this germ could assume a more important
      role in bacterial meningitis comparable to that in the pre-antibiotic era.

PMID- 9005525
TI  - [Prevalence of transmission of zidovudine-resistant viruses in Switzerland.
      l'Etude suisse de cohorte VIH].
AB  - Zidovudine (ZDV) was the most widely used anti-HIV drug between 1987 and 1995,
      and, as already reported, transmission of ZDV-resistant viruses occurs. Several
      mutations of the reverse transcriptase gene have been identified; one of them
      affects the 215 codon and is associated with a high degree of resistance. We have
      determined, using selective PCR, the prevalence of transmission of 215 mutant
      isolates in 134 patients with primary HIV infection (PHI) and have identified 8
      patients with 215 mutant virus between 1989 and 1995 in Switzerland. Mutant
      resistant viruses have been isolated from patients treated with most antiviral
      drugs. A systematic search for mutant viruses may provide useful information for
      the adaptation of treatment strategies.

PMID- 9005526
TI  - [Are inhaled dust particles harmful for our lungs?].
AB  - Particles with diameters ranging from less than 0.02 to more than 100 microns and
      in concentration up to 120 micrograms/m3 daily average TSP (total suspended
      particles) are measurable in the air of Swiss cities and responsible for the
      decrease of visibility on the Swiss Plateau and south of the Alps. The particle
      size shows a typical distribution: the coarse particles (> 2.5 microns mass
      median diameter) are mostly of natural origin (plants, pollen, earth particles)
      and are deposited in the upper airways. The fine particles (PM2.5 < 2.5 microns)
      are predominantly deposited into the alveolar space. These fine and ultrafine
      particles (< 0.02 microns) are produced by the burning of fossil fuels or by
      photochemical reactions. By bypassing the mucociliary and cellular defense
      mechanisms, fine particles can invade the lung parenchyma and cause an
      inflammatory response. The additional chemical layering of a carbon core by
      nitrates, sulfates and other organic materials and metals such as iron cause
      greater local oxidative and/or carcinogenic damage than in the vaporized state.
      In comparing worldwide epidemiological studies, there seems to be a cohesive and
      consistent relationship between increases of particle concentration and the
      increase of mortality (mostly among patients over 65 with concomitant lung and
      heart diseases and among smokers) and morbidity (bronchitis, pneumonia, COPD,
      and, less convincingly, asthma). An increase in daily average PM10 (particles <
      10 microns) is correlated with an increase in mortality not related to accidents
      and suicides of 1.0% for the same and/or the following days. In Switzerland, mean
      annual concentrations of 14-53 micrograms/m3 TSP or 10-33 micrograms/m3 PM10,
      well below the national standard (annual mean TSP 70 micrograms/m3) have been
      measured in rural and urban areas. Even at these concentrations an increase in
      respiratory symptoms and a decrease in lung function, without evidence for a
      "safe" threshold, have been observed in the Swiss study of air pollution and lung
      diseases in adults (SAPALDIA). Although the noxious effects of the particles
      cannot be clearly separated from the effect of other pollutants (e.g. NOx, SO2,
      ozone) in complex pollutant mixtures, the emission standards and national
      standards for ambient air should be revised, in particular by adding a standard
      for fine particles (e.g. PM10 or PM2.5).

PMID- 9005528
TI  - [Heart-kidney transplantation of the same donor following failure of a first
      renal transplantation due to chronic rejection].
AB  - Combined heart and renal transplantation from the same donor is an uncommon
      procedure. We describe the case of a patient with prior kidney transplantation
      whose renal graft had to be removed a few years later because of chronic
      rejection. The patient then developed severe hypertensive and ischemic left
      ventricular dysfunction. Combined heart and kidney transplantation was performed
      several years after the first renal transplantation. This observation is the
      first description of a combined heart and kidney transplantation after removal of
      a former renal graft whose failure was due to chronic rejection. Great care was
      taken to avoid identical MHC antigens (HLA-A; -B; -DR) between the two donors, to
      prevent recurrent rejection of the grafted organs. After 18 months, no rejection
      was detected in either organ. This case report confirms the feasibility of this
      complex procedure, provided care is taken to avoid identical HLA groups between
      the two donors so as to reduce immunological complications.

PMID- 9005529
TI  - [Pericarditis in chronic inflammatory bowel disease: underlying disease or side
      effects of therapy? Clinical problem solving].
AB  - Pericarditis and myocarditis are rare extraintestinal manifestations of chronic
      inflammatory bowel disease (ulcerative colitis and Crohn's disease). Pericarditis
      as a side effect induced by sulfasalazine or 5-aminosalicylic acid, drugs used in
      the therapy of these diseases, was first described only 7 years ago. In older
      case reports the relationship between the use of these drugs and pericarditis is
      unclear. We analyze the reported cases of 68 patients (38 men, 24 women) with
      ulcerative colitis (n = 45) or Crohn's disease (n = 15) who had one or more
      episodes of pericarditis or myopericarditis. Pericarditis was not associated with
      high activity of bowel disease in all cases. In most cases therapy with
      corticosteroids led to uneventful recovery. In drug induced pericarditis omission
      of the 5-ASA therapy was sufficient in a few cases. There was one fatal case
      (with myocarditis). The decision whether pericarditis is a symptom of the
      underlying disease or a side effect of the drug used for the treatment of the
      disease is not always easy. We present an analysis (clinical problem solving) of
      a pertinent observation in a patient with Crohn's disease and pericarditis,
      showing the dilemma of pericarditis in chronic inflammatory bowel disease and its
      therapy.

PMID- 9005527
TI  - [Reproducibility of fasting serum cholesterol and triglycerides in ambulatory
      patients with mixed hyperlipidemia].
AB  - Intraindividual variability of serum lipid concentrations in normal volunteers
      and in patients with hyperlipidemia is substantial. The aim of this study was to
      investigate prospectively the reproducibility of fasting serum triglyceride and
      total cholesterol concentrations in primary health care patients with combined
      hyperlipidemia, i.e. under conditions of daily medical practice. Secondary forms
      of hyperlipidemia were excluded. 19 general medical outpatients with primary
      combined hyperlipidemia were studied. Serum total cholesterol and triglyceride
      concentrations were measured after an overnight fast at 08.00 h 4 times at weekly
      intervals. To study the influence of alcohol intake on serum lipid
      concentrations, total cholesterol and triglycerides were measured without alcohol
      influence and 12 hours after consumption of a mean of 100 g alcohol in the
      evening. In 19 patients (10 males, 9 females, mean age 55 years, body mass index
      27.9 +/- 4.4 kg/m2), mean +/- SD of serum triglycerides was 3.97 +/- 1.8 mmol/l
      and of total cholesterol 7.9 +/- 1.8 mmol/l. The combined intraindividual and
      interassay coefficient of variation was 18.7 +/- 8.2% for triglycerides and 5.1
      +/- 2.5% for total cholesterol. Fasting serum triglycerides (3.5 +/- 1.1 vs. 3.7
      +/- 1.4 mmol/l) and total cholesterol (7.6 +/- 1.4 vs. 7.8 +/- 1.0 mmol/l) did
      not significantly change 12 hours after acute alcohol consumption. Patients with
      primary combined hyperlipidemia in a primary health care setting show small
      intraindividual variations of overnight fasted serum triglyceride and total
      cholesterol concentrations. Moderate alcohol consumption 12 hours before blood
      sampling does not significantly affect triglyceride and cholesterol values.

PMID- 9005530
TI  - [Guidelines for mechanical home ventilation. SVTL (Swiss Society against
      Tuberculosis and Lung Diseases). SGP (Swiss Society for Pneumology)].

PMID- 9005531
TI  - [Re: Fahrlander H: Medical, legal and ethical problems in persistent vegetative
      state (Schweiz Med Wochenschr 1996; 126: 1191-1195)].

PMID- 9005532
TI  - [Re: Roth F: What is our approach concerning patients in persistent vegetative
      state (PVS)? (Schweiz Med Wochenschr 1996; 126: 1187-1190) and Fahrlander H:
      medical, legal and ethical problems in persistent vegetative state (Schweiz Med
      Wochenschr 1996; 126: 1191-1195)].

PMID- 9005533
TI  - [Genioplasty. The long-term results after chin osteotomies with stable
      osteosynthesis].

PMID- 9005534
TI  - [Collegiality: a theme for yesterday's people?].

PMID- 9005536
TI  - [The state of the art of endodontics].

PMID- 9005535
TI  - [Computer assisted radiology. The 10th International Symposium CAR 96 of 26 to 29
      June 1996 in Paris].

PMID- 9005537
TI  - [Decision strategies. The 17th annual meeting of the SSPD of 6 September 1996 in
      Geneva. Societe Suisse de Prothese Dentaire].

PMID- 9005538
TI  - [Bioesthetics and controversies. The 26th annual congress of the Societe Suisse
      de Parodontologie in Zurich].

PMID- 9005539
TI  - [Under-stand, in order to understand other people].

PMID- 9005540
TI  - [Teaching: "modern times"].

PMID- 9005541
TI  - [The effect of a disinfecting solution on the technical quality of reversible
      hydrocolloid impressions].

PMID- 9005542
TI  - [Vomiting: causes and therapy].
AB  - Vomiting can be a symptom of serious disease. Although it is important to
      correctly diagnose the cause of vomiting so the underlying disease can be
      treated, often antiemetic drugs must be used for the well being of the patient.
      First the physiology of vomiting with the neurotransmitter receptor system and
      the neuroanatomical neuron pathway is reviewed. Then a synopsis of antiemetic
      drugs currently used in veterinary medicine is presented with classification
      according to receptor antagonism. Finally novel drugs used to control vomiting in
      human patients and which may play a future role for the veterinary patient are
      discussed.

PMID- 9005544
TI  - [Diagnosis and medical care of raptors in a compilation of cases from 1985-1994].
AB  - This article summarises the clinical findings in 554 birds of prey, that were
      admitted to the zoo animal and exotic pet clinic of the veterinary faculty in
      Zurich between 1 January 1985 and 31 December 1994. Details on the diagnosis,
      therapy and prognosis are intended to give the practitioner information on the
      possibilities for the management of diseased raptors. However, it has to be
      emphasized that the ultimate goal of treatment has to be the rehabilitation of an
      animal that will be able to survive to a suitable environment. The data presented
      shows that 31% of the birds of prey were successfully released. The most frequent
      reason for admission was trauma and 47% of the patients had one or more
      fractures. But only one out of three fractures was considered suitable for
      treatment. The management of birds that are starving is a challenge because they
      require a special dietary regimen. Successful work in the field of the treatment
      and rehabilitation of raptors requires detailed knowledge of their biology and
      medicine.

PMID- 9005543
TI  - [Eye injuries in the dog caused by cat claws].
AB  - A retrospective study of ocular cat claw injuries in the dog revealed an over
      representation of very young dogs in our case material. Puppies up to the age of
      12 weeks have no menace response. Thus, an important protective mechanism is
      missing in early life. This may be one reason for the frequently occurring severe
      ocular trauma caused by cat claw injuries in puppies. Older dogs are less likely
      to sustain such an injury. Cat claw injuries cause corneal and lens capsule
      perforation with ensuing severe phacoclastic uveitis. In our series phthisis
      bulbi or secondary glaucoma were the result in 50% of the cases. In large lens
      capsule tears early lens extraction may prevent severe uveitis and may retain
      functional vision.

PMID- 9005545
TI  - [What is your diagnosis? Haemobartonellosis in a cat].

PMID- 9005546
TI  - Financial interests constrain drug development.

PMID- 9005547
TI  - Selling science: at what price?

PMID- 9005548
TI  - Judgement pries open expert panel.

PMID- 9005549
TI  - The reluctant man of the year.

PMID- 9005550
TI  - The media's love affair with AIDS research: hope vs. hype.

PMID- 9005551
TI  - African malaria studies draw attention.

PMID- 9005552
TI  - How to get databases talking the same language.

PMID- 9005553
TI  - Integrating the biological sciences in New Mexico.

PMID- 9005554
TI  - New "guiding" protein discovered.

PMID- 9005555
TI  - Synapse elimination: for nerves it's all or nothing.

PMID- 9005556
TI  - Potency of combined estrogenic pesticides.

PMID- 9005558
TI  - [No need to fear radical debridement].

PMID- 9005557
TI  - Polyalanine expansion in synpolydactyly might result from unequal crossing-over
      of HOXD13.

PMID- 9005559
TI  - [Covering soft tissue defects].
AB  - In the past, the main emphasis in the treatment of complex limb injuries was
      placed upon the reconstruction of bony defects. Recently, however, reconstructive
      soft-tissue procedures have gained the attention they deserve. The salvage of a
      severely injured extremity depends rather on the feasibility of reconstructive
      surgical tissue procedures than on restoration of the bony defect. Sufficient
      vascularity is an essential condition for fracture healing and the prevention of
      post-traumatic complications like osteomyelitis and pseudarthrosis. If primary
      closure of a soft-tissue defect is not possible, preliminary covering has to be
      obtained with artificial skin replacement (vacuum sealing) until definitive
      covering with muscle or musculocutaneous flaps can be achieved. With the
      microvascular restorative techniques available today even complex soft-tissue
      problems can be solved. Nevertheless, an appropriate infrastructure and a trained
      and skilled surgeon are essential.

PMID- 9005560
TI  - [Radiologic evaluation of acetabular defects on acetabular loosening of hip
      alloarthroplasty].
AB  - In 18 human pelvis specimens we produced different acetabular defects according
      to Paprosky. Standardized X-rays of these specimens were taken, and these X-rays
      were evaluated by six orthopaedic surgeons with different levels of surgical
      experience. A total of 350 evaluation sheets were analyzed. The X-rays of the
      acetabular rim were correctly interpreted in only 66% of cases. The
      interpretation of plates showing bone loss was even worse. A medial wall defect
      was correctly assessed in just 49% of cases, giving a correlation (r) or 0.60
      between the real defect and the radiological estimation. While massive defects
      were recognized in most cases, moderate defects were correctly estimated in about
      50%. Moderate defects included migration of the cup, which was overlooked in
      between 46% and 69% of cases. Similar results were achieved in the judgement of
      bone loss. Only in 25% was direct classification according to Paprosky
      successful; it was better in small defects and worse in massive defects, with
      16%. The interobserver correlation was only 0.54. In general, in most cases the
      defects were underestimated. This study raises the question of whether
      classification systems can provide the information needed for clinical useful
      therapeutic algorithms. The fact that the real bone loss is generally
      underestimated must receive due considerations when operations are being planned.

PMID- 9005562
TI  - [Long-term outcome of managing medial femoral neck fractures with ceramic head
      endoprostheses].
AB  - Total hip replacement is often recommended for the treatment of femoral neck
      fractures in elderly patients. A less invasive approach with shorter operating
      time is the replacement of the femoral head only, leaving the acetabular
      cartilage in situ. Hemiarthroplastic hip replacement using a metallic head
      prosthesis was not successful in the past, because the majority of patients
      developed protrusio acetabuli after surgery. In the present study
      hemiarthroplastic hip replacement using an Al2O3-ceramic head was shown to be a
      useful method for the treatment of femoral neck fractures in elderly patients.
      From 1985 to 1990 277 patients were treated with hemiarthroplasty. The average
      age at the time of accident and operation was 81.7 years. At the time of follow
      up in 1993 only 77 survivors were available for examination. A standardized score
      was calculated assessing activity, gait, hip pain, etc., with the patients
      obtaining an average score of 58 out of possible 78 points. Only three patients
      had hip pain, and in four cases the roentgenographic examination revealed
      protrusio acetabuli. Two of these four patients underwent revision surgery for
      replacement of the cup, leaving the stem in situ. In view of the small number of
      approach-related complications, hemiarthroplastic hip replacement using an Al2O3
      ceramic head 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- 9005561
TI  - [Severe pelvic injury with pelvic mass hemorrhage: determining severity of
      hemorrhage and clinical experience with emergency stabilization].
AB  - The blood loss during the acute period after complex pelvic trauma is finally
      responsible for the high mortality associated with this specific type of injury.
      Several protocols have been published for optimized management, but up to now
      comparable data are not available as no exact definitions exist judging the
      severity of trauma and blood loss. As part of a prospective study 19 patients
      after unstable pelvic injuries with unstable circulation underwent emergency
      stabilization by the pelvic C-clamp. Beside standard clinical parameter the
      initial hemoglobin value was converted into a "blood volume equivalent". 18 of
      the 19 patients had an injury severity according to group III and IV of the
      Hannover Polytrauma Score (PTS). Concommitant abdominal injuries were seen in 12
      cases (23 injuries), concommitant urological injuries in 12 cases (14 injuries).
      In 13 cases the pelvis was the major source of bleeding in 9 cases an additional
      intraabdominal hemorrhage was observed. 11 patients died due to sequelae of their
      injury, 8 patients survived. Although the initial blood loss was comparable both
      in the group of the deceased patients and the survivors, a 44% higher subsequent
      blood substitution (= 10089 ml) was observed in the nonsurvivor group. In
      conclusion the data proofed that early control of hemorrhage is fundamental for
      the prognoses after complex pelvic trauma. The estimation of the blood loss may
      help in indicating aggressive emergency procedures like emergency stabilisation,
      pelvic clamps, surgical exploration and tamponade. This calculation may be a
      basis for a more detailed analyses of this devastating injury and judging the
      benefit of different management protocols.

PMID- 9005563
TI  - [Criteria for radiologic evaluation of cement-free hip endoprostheses exemplified
      by the Spotorno shaft].
AB  - Roentgenographic evaluation of total hip arthroplasty is based on changes in the
      marginal zones and in position. The changes in the marginal zones are not subject
      to any general rule. They are characteristic for the type of prosthesis. In a
      retrospective study, the roentgenographic findings of 431 spotornofemoral
      components were evaluated. We analyzed the X-ray pictures of 15 explanted
      spotornostems in comparison to the pictures of 15 spotornostems that were known
      to be stable because of revision surgery. We used this method to establish signs
      of stem loosening. Regression of more than 2 mm and a change in position toward
      varus or valgus were observed only in loose prostheses. We therefore considered
      these radiological changes to be an indication of loosening. Radiolucent lines up
      to 2 mm wide are typical for the spotornostem in the area of the prosthesis
      shoulder and the calcar region; when they appear in the mid- or distal section,
      they are also considered an indication of loosening. Radiolucent lines more than
      2 mm wide indicate loosening in any case. Early in the postoperative course, the
      parameter of the femoral canal is already much lower in loose prostheses than in
      stable prostheses. An ill-fitting position in the femoral canal therefore shows a
      poor prognosis. Local hypertrophy of the femoral cortex or a base formation were
      more common in loose spotornostems. We also considered these changes to be
      indicator of an unfavorable prognosis.

PMID- 9005564
TI  - [Clinical value of conventional radiology and MRI in assessing osteochondrosis
      dissecans stability].
AB  - A prospective study was performed on 72 patients with osteochondritis dissecans
      (OD) of the knee and ankle to compare plane radiography, MRI and arthroscopy
      before therapeutic procedures. Special interest was placed on the assessment of
      fragment stability with radiological methods for staging related therapy. OD was
      localized in 46 cases on the femoral condyle and in 26 cases on the talus.
      Radiological methods were performed simultaneously and shortly before definite
      arthroscopical therapy. Using conventional radiography, OD of the condyles was
      staged according to the classification of Rodegerdts and Gleissner and OD of the
      talus suggested by Berndt and Harty. MRI staging was performed by morphology of
      the interface of the OD. Arthroscopical staging based on the classification of
      Guhl. There was an excellent correlation between the stages in MRI and
      arthroscopy, showing correct prediction of stable and unstable fragments in 92%.
      In contrast, fragment stability could not be efficiently assessed by conventional
      radiology because fragments could be stably fixed in cases of bony separation.
      MRI is indicated before performance of staging-related therapy of OD to select
      patients with stable fragments for conservative therapy and those with unstable
      OD for surgical therapy.

PMID- 9005565
TI  - [Added work of breathing, respiratory pattern and determination of ventilator
      weaning readiness in inspiratory pressure support and and automatic tube
      compensation].
AB  - We measured the ventilatory pattern and additional work of breathing (WOBadd) at
      three different levels of inspiratory pressure support [IPS 5, 10, 15 mbar above
      positive end-expiratory pressure (PEEP)] and in a new ventilatory mode, automatic
      tube compensation (ATC), in nine operative patients without lung injury nine
      patients ventilated for several following acute respiratory insufficiency (ARI).
      In ATC, endotracheal tube resistance is compensated automatically by means of
      closed-loop control of the calculated tracheal pressure. Pressure support in this
      mode, i.e. airway pressure above PEEP, is equal to the actual flow-dependent
      pressure drop across the endotracheal tube (ETT). Airway pressure rises at the
      beginning of inspiration and falls towards the end. As the tube resistance of ETT
      seriously hinders expiration and can cause desynchronization between ventilator
      and patient, airway pressure is reduced below PEEP during expiration in the same
      way as it is increased during inspiration. The result is a near-constant tracheal
      pressure at PEEP both during inspiration and during expiration. This mode could
      be best termed as "electronic extubation". The most striking difference between
      the postoperative patients and the ARI patients was their minute ventilation
      (17.8 +/- 1.85 l/min in ARI patients vs 7.3 +/- 3.1 l/min in the postoperative
      patients). In the postoperative patients augmentation of IPS from 5 to 15 mbar
      induced a steady increase in tidal volume (VT) and a consecutive decrease in
      respiratory rate (rr) compared with ATC (VTATC,postop = 463 +/- 78 ml;
      rrATC,postop = 16 +/- 4 min-1; VTIPS5.postop = 505 +/- 79 ml; rrIPS5,postop = 15
      +/- 4 min-1; VTIPS10,postop = 562 +/- 86 ml; rrIPS15,postop = 14 +/- 4 min-1;
      VTIPS15.postop = 660 +/- 151 ml; rrTPS15,postop = 12 +/- 4 min-1), whereas the
      augmentation of IPS of 5 and 10 mbar in the ARI patients could not compensate for
      the increase in rr and the decrease in VT, after switching from ATC to IPS
      (VTATC,ARI 724 +/- 308 ml, rrATC,ARI = 24 +/- 6 min-1; VTIPS5,ARI = 649 +/- 315
      ml; rrIPS5,ARI = 27 +/- 8 min-1; VTIPS10,ARI = 653 +/- 353 ml; rrIPS10,ARI = 25
      +/- 8 min-1: Even IPS 15 was not able to reestablish VT at the values observed
      during ATC (VTIPS15,ARI = 680 +/- 312 ml). During ATC WOBadd was small in both
      postoperative and ARI patients (WOBadd,ATC,postop = 93 +/- 36 mJ/l,
      WOBadd,ATC,ARI = 116 +/- 72 mJ/l). In the postoperative patients, an inspiratory
      pressure support of 5 mbar was not sufficient to compensate WOBadd compared with
      ATC. However, IPS 10 and 15 mbar were able to compensate for WOBadd
      (WOBadd,ATC5.postop WOBadd,IPS5,postop = 189 +/- 77 mJ/l; WOBadd,IPS10,postop =
      55 +/- 30 mJ/l; WOBadd,IPS15,postop = 21 +/- 11 mJ/l). In the ARI patients an IPS
      5, 10 or 15 mbar was not sufficient to compensate for WOBadd (WOBadd,IPS 5,ARI =
      1126 +/- 262 mJ/l; WOBadd,IPS 10,ARI 863 +/- 253 mJ/l; WOBadd,IPS15,ARI 763 +/-
      298 mJ/l). Under ATC, WOBadd was only 15% of WOBadd under IPS of 15 mbar. All but
      two patients were successfully extubated after the investigation. These two
      patients were not extubated because they were dependent on an FIO2 > 0.5. Our
      results strongly indicate that ventilatory dependence in ARI patients may be
      caused by the ETT rather than by mechanical dysfunction of the lung. ATC is a
      very helpful mode to use in distinguishing between ventilatory failure caused by
      ETT and real ventilatory dependence.

PMID- 9005567
TI  - [Comparison and outcome of grade II and III acromioclavicular joint injuries].
AB  - Eighty-five patients with grade 2 or grade 3 sprains of the acromioclavicular
      (AC) joint were evaluated clinically and radiographically 32 months after injury.
      Group I included 34 patients with grade 2 sprains (Tossy II) and group II
      included 51 patients with grade 3 injuries (Tossy III). In group I, 15 patients
      were treated surgically (group Ia) and 19 patients were treated conservatively
      (group Ib), while in group II, 41 patients were treated surgically (group IIa)
      and 10 patients were treated conservatively (group IIb). At surgery open
      reduction and transarticular fixation of the AC joint with Kirschner wires was
      performed. Conservative treatment included the initial use of a sling or a
      knapsack bandage and early performance of range-of-motion exercises. Shoulder
      function was assessed according to the score devised by Constant and Murley. In
      both groups, 97 of 100 possible points (minimum 72, maximum 100) were obtained
      after conservative and after surgical treatment. Nine of 10 patients (90%) with
      grade 3 sprains (group IIb) had more pronounced displacement and increased
      mobility of the lateral end of the clavicle after conservative treatment. After
      surgery, dislocation and increased horizontal, mobility of the lateral end of the
      clavicle occurred in 18 (44%) of 41 patients with grade 3 sprains (group IIa P <
      0.0001). However, these findings did not correlate with the functional outcome.
      At follow-up there was a significant increase in degenerative changes seen on
      radiographs (P < 0.035) in all patients. Again these findings did not correlate
      with the functional outcome. More degenerative radiological changes were observed
      in patients who had undergone surgery (P < 0.003). Patients with grade 2 sprains
      were more frequently restricted in sporting activity after surgery (P < 0.05).
      Patients with grade 3 sprains who were treated surgically complained of pain more
      frequently (P < 0.01), and they returned to work later than patients who were
      treated conservatively after grade 3 sprains. An additional rehabilitation
      program guided by a physiotherapist seemed to have no impact on the functional
      outcome. A total of 56 patients were treated by surgery. Among these patients 11
      complications occurred, requiring five additional surgical procedures. Among 29
      conservatively treated patients, only in 1 patient did subacromially located
      arthritic changes of the AC joint have to be removed.

PMID- 9005566
TI  - [Results of primary unreamed tibial nailing of tibial fractures with severe open
      or closed soft tissue injuries].
AB  - Primary stabilization was performed in 72 tibial fractures with sever open (n =
      37) or closed (n = 35) soft tissue injury using unreamed interlocking nails. In
      60 (83%) cases the fractures healed without additional procedures. There were 2
      cases of osteitis, but both these fractures healed after removal of the nail or
      after reamed nailing. In 9 patients with delayed union reamed nailing (n = 8) or
      bone grafting (n = 1) led to healing. In 1 patient with hypertrophic
      pseudarthrosis, union was achieved after substitution of a reamed nail for the
      anreamed nail. The infection rate was similar to that observed with external
      fixation. More secondary procedures, such as bone grafting or a change of the
      osteosynthesis technique, are necessary with external fixation than with unreamed
      nailing. Further advantages of unreamed nailing are the internal treatment of the
      fracture and the patient's greater comfort. Therefore, unreamed nailing can be
      recommended for the primary treatment of tibial fractures with severe open or
      closed soft tissue trauma.

PMID- 9005568
TI  - [Late outcome after intermuscular ulnar nerve transposition in trauma surgery
      indications].

PMID- 9005569
TI  - [Bone and joint infections].

PMID- 9005570
TI  - [Bilateral luxatio erecta of the shoulder joint--a rare injury. Management and
      therapy in polytrauma patients].
AB  - The case of a 36-year-old male patient is reported who fell from 20 m, sustaining
      injuries to the abdomen and pelvis and fractures of both arms and the left leg as
      well as erect dislocation of both shoulders (luxatio erecta humeri). The injury
      on the right was subcoracoid, that on the left subglenoid-a compound dislocation
      of the humerus head through the axilla. Based on this case and the pertinent
      literature, the pathophysiology, diagnosis and treatment of this rare injury are
      discussed. After immediate closed reduction, soft tissue damage, fractures or
      neurovascular lesions should be operated on as soon as possible.

PMID- 9005571
TI  - [Neurotrauma. Current treatment concept].

PMID- 9005572
TI  - [Complex trauma of the knee joint. Diagnosis--management--therapeutic
      principles].
AB  - The complex nature of combined fractures and soft tissue injuries of the distal
      femur and proximal tibia needs special attention and specific management. Distal
      femoral and proximal tibial fractures in young patients are usually caused by
      high-energy trauma. They are complicated by a high rate of systemic and local
      injuries to cartilage, ligaments and skin. This small but important group with
      severe injuries needs a detailed treatment algorithm, because despite the
      treating surgeon's skill, enthusiasm and wishful thinking, these injuries
      frequently lead to unsatisfactory results. The combination of distal femoral
      fractures and proximal tibial fractures was defined as complex knee injury type
      1; the combination of distal femoral fractures or proximal tibial fractures with
      second or third degree open or closed soft-tissue injury was defined as complex
      knee injury type 2; knee dislocations were defined as complex knee injury type 3.
      A decision-making scheme is presented specifically addressing timing and
      treatment modalities. Out of 116 type 1 and 2 complex knee injuries, 8 had a deep
      infection, in 6 cases an amputation was carried out and in 4 cases a knee
      arthrodesis was performed. In 81 isolated distal femoral fractures, only 4 had a
      deep infection, none needed amputation, and in only 1 case did a knee arthrodesis
      have to be performed. The average Neer Score in 90 followed-up complex knee
      injuries, types 1 and 2, was 76.5 +/- 13.5 compared with 82.8 +/- 10 (out of 54
      isolated distal femoral fractures). Out of 37 cases with knee dislocation, 22
      (60%) had an poor result according to the Lysholm Score (average Lysholm Score
      60.7 +/- 28).

PMID- 9005573
TI  - [Midline and vertex epidural hematomas: clinical aspects, surgical indications
      and therapy].
AB  - Within a group of 315 epidural haematomas treated surgically 8 (2.5%) were
      located within the midline or at the vertex. The clinical symptoms may be small
      in frontally located haematomas. Paraparesis is caused by a haematoma localized
      at the vertex. The latter may be misinterpreted as a spinal trauma. The
      recognition of the hyperdense blood within the last slices of normal CT scans
      needs experience. It has been misinterpreted as hyperostosis of the skull. We
      present a group of eight personal cases. The sagittal skull suture was fractured
      in seven patients. One patient already had an 11-month history. Four cases were
      primary and had not been recognized. The prognosis depends on concomitant primary
      brain injuries. Early diagnosis with operative treatment given the best chance.
      Polytraumatized patients with concomitant injuries die. Slowly developing
      haematomas do not require acute surgery by in experienced surgeons. Sagittal
      sinus laceration must be treated by experienced neurosurgeons. It can be closed
      by suturing the dura to the bone with implanted collagen. In subacute cases the
      stiffness of the dura allows no normalization of the dura position. A dural graft
      is necessary for repositioning.

PMID- 9005574
TI  - [The injury pattern in polytrauma. Value of information regarding accident
      process in clinical acute management].
AB  - To investigate the correlation between the mechanism of an accident and the
      resulting injury pattern we reviewed the data of 195 prospectively documented
      multiply traumatized patients. Information on the accident was based on
      descriptions given by eye witnesses, police and the emergency medical staff. Only
      moderate to severe lesions (AIS > or = 3; Abbreviated Injury Scale Version 1990)
      of each body region were analyzed. The mean injury severity (ISS) for all these
      patients was 39.5 (18-75); the lethality was 34%. Different types of accidents
      led to various injury patterns. We found a high incidence of lesions of the head
      in frontal (F) motor vehicle crashes (MVC) nonbelted (76%), of the chest in
      lateral (L) MVCs (80%), of the abdomen in F MVCs belted and in LMVCs (60%), of
      the pelvis after suicidal fall (SF; 69%) and of the lower extremities in
      motorcycle accidents (90%), SFs (69%) and collisions with a train (67%). Severe
      lesions of the spine were frequently seen after accidental falls (41%), SFs (30%)
      and F MVCs belted (25%). There was a very substantial difference in the injury
      pattern after suicidal jump (26% head, 69% pelvis, 65% lower extremity lesions).
      and accidental fall (54% head, 19% pelvis, 23% lower extremity lesions). As a
      result of the correlation with specific injury patterns, the preceding mechanism
      of accident should be exactly documented and considered by the physician during
      the early phase of resuscitation.

PMID- 9005575
TI  - [Feasibility and complications in early enteral nutrition of severely injured
      polytrauma patients via duodenal tubes].
AB  - Early enteral nutrition is widely accepted for its support of organ structure and
      function ("gut injury hypothesis") and reduction of infectious complications and
      hypermetabolism in critically ill postoperative or postinjury patients. Nineteen
      severely injured patients (Injury Severity Score 40.3 +/- 11.6) were studied for
      the feasibility of early enteral nutrition via a duodenal feeding tube. Despite
      maxillary fractures, rhinoliquorrhea and blunt abdominal trauma the enteral
      feeding was mostly started immediately after trauma. Intermittent diarrhea or
      constipation resolved after reduction of the feeding rate within 1 or 2 days.
      Total enteral nutrition could not be realized in all cases; a central venous line
      was always additionally necessary. However, the goal was not complete enteral
      nutrition but a continuous enteral supply to maintain the integrity of the gut.
      The study has shown that early enteral nutrition via a duodenal feeding tube is
      also feasible in severely injured patients. The expenditure to overcome the
      technical and organizational problems seems to be justified. Enterally fed
      patients may have a better outcome that those in whom only parenteral is
      employed.

PMID- 9005576
TI  - [Perilunate dislocation and dislocation fractures--results of surgical
      management].
AB  - We report 22 patients who sustained a perilunate dislocation (PD) with or without
      a fracture of the scaphoid. The carpal ligaments were explored and reattached in
      all cases. The fractured scaphoid in perilunate fracture dislocations (PFD) was
      stabilised by a Herbert screw in 13 cases and in one case with a Matti-Russe bone
      graft. After an average of 5 years the clinical score of Green and O'Brien showed
      good results for both PD and PFD. Patients with PFD had less pain and better grip
      than the patients with PD. The sagittal range of motion (average between 70
      degrees and 99 degrees) and the subjective limitation in sports and work were
      equal for PD and PFD. The only open injury (PD) had the worst clinical result.
      All patients with PD showed a carpal instability dissociative of the proximal row
      (CID) and an arthrosis of the radiocarpal joint. In the patients with PFD a CID
      could be seen in 78% and an arthrosis in 93%. A carpal collapse occurred in 75%
      of cases after PD and in 29% after PFD. In 57% of cases the PFD was accompanied
      by a disruption of the SL ligament. The anatomical reconstruction of the scaphoid
      is essential for good carpal alignment. The stable fixation of bony avulsions
      showed good results. A CID could not be avoided in any of our patients with PD.

PMID- 9005577
TI  - [Hemi-arthroplasty--primary or secondary measure for 3- and 4-fragment fractures
      of the proximal humerus in the elderly?].
AB  - Successful treatment of three- and four-part proximal humerus fractures is a
      therapeutic challenge to the surgeon, particularly in the case of elderly
      patients. Open reduction and internal fixation have been advocated, but have not
      consistently produced acceptable results. The results of humeral head replacement
      as a salvage procedure after non-union or failed open reduction and internal
      fixation are less predictable. The outcome of hemiarthroplasty (Neer II)
      performed for three- and four-part proximal humerus fractures in elderly patients
      was studied. The average patient follow-up was 42.9 months (range 5-98). Eighteen
      women and eight men with an average age of 64.5 years were evaluated according to
      the UCLA. Constant-Murley and HSS Score. A Visual Score (0-100 points) was also
      used. Hemiarthroplasty was performed in 11 patients within 4 weeks of trauma and
      in 15 patients after 4 weeks. Fair, good, or excellent results were achieved in
      80% (UCLA and Visual), 73% (HSS) and 46% (Constant-Murley) of the patients,
      respectively. Ninety-six percent of the patients reported only slight or no pain.
      The range of motion was limited in almost all cases. The outcome was not
      significantly influenced by age, sex and follow-up time. However, there was a
      significant correlation between the outcome and the length of time between injury
      and humeral head replacement (r = -0.5). The outcome after early hemiarthroplasty
      was better than after late humeral head replacement (UCLA: 27.1 +/- 4.6 vs 22.5
      +/- 5.6 P = 0.04; Constant-Murley: 65.6 +/- 18.5 vs 47.5 +/- 18.6, P = 0.02; HSS:
      74.0 +/- 14.4 vs 63.5 +/- 17.6, P = 0.17). Self-assessment did not differ between
      these two groups. After early hemiarthroplasty, active forward flexion was
      significantly better. This study indicates that early humeral head replacement
      for three- and four-part proximal humerus fractures in elderly patients achieved
      better functional outcome than delayed humeral head replacement. The decision to
      perform prosthetic humeral head replacement in these cases should be made as
      early as possible after trauma.

PMID- 9005578
TI  - [Traumatic hemarthrosis of the knee joint--clinical significance of nuclear
      magnetic resonance tomography].
AB  - A prospective study was performed on 94 patients with hemarthrosis of the knee to
      assess the value of MR imaging (MRI) in detection of bleeding sources and
      selection of therapy modalities. Patients were examined clinically within a week
      after knee trauma; the investigations performed included puncture of the joint to
      confirm hemarthrosis, a conventional X-ray to exclude fractures, MRI and
      arthroscopy. MRI was performed for diagnosis of acute lesions, definition of
      bleeding sources by morphological criteria, and allocation of patients to
      conservative or surgical therapy. Arthroscopy was performed to control MRI, to
      visualize bleeding sources, and to maintain therapy if necessary. The 94 patients
      were found on arthroscopy to have a total of 123 bleeding sources, which were
      correctly defined by MRI in each of 107 cases as an acute lesion communicating
      with the joint space; 16 bleeding sources were not found and there were 10 false
      positive reports. In keeping with our treatment strategies, arthroscopy disclosed
      lesions requiring surgical therapy in 77 of 94 patients (82%) and lesions that
      would be adequately treated by conservative therapy in 17 of 94 patients (18%).
      MRI predicted surgical or conservative therapy correctly before arthroscopy in 83
      of 94 patients (88%). In conclusion, MRI has a high predictive value in
      definition of acute lesions that will lead to hemarthrosis of the knee. This
      noninvasive method allows screening out of the relatively small portion of
      patients without severe lesions, who then do not have to be subjected to further
      invasive therapy.

PMID- 9005579
TI  - [Analysis of implantation-induced nail deformation and roentgen morphometric
      studies as the principle for an aiming device for distal interlocking nailing
      without roentgen image intensification].
AB  - While working to develop a distal locking device, we analyzed distal nail
      position with reference to nail deformation and a radiographic-morphometric
      investigation. The amount and the direction of implant deformation in unslotted
      stainless steel unreamed tibial nails (Synthes) were analyzed. Measurement of
      implant deformation (3 translations, 3 angles) in the center of the distal
      transverse locking hole was performed with a 3D magnetic motion tracker system
      before and after nail insertion. Unreamed tibial nails (diameter 8 mm, n = 10;
      diameter 9 mm, n = 10) were inserted in paired human cadaver tibiae. The results
      showed lateral translations of -4.5 +/- 3.5 mm (mean and standard deviation,
      range 14.3 mm) and dorsal translations of -7.8 +/- 5.8 mm (mean and standard
      deviation, range 19.2 mm). Rotational deformations around the longitudinal axis
      of the nail were 0.3 +/- 0.7 degree (mean and standard deviation, range 2.4
      degrees). The results showed, that a simple aiming arm, mounted on the proximal
      nail end, alone or even in combination with a large working channel (e.g. 10 mm
      in diameter), was not adequate to the aiming process. A radiographic-morphometric
      analysis was subsequently performed in 40 tibiae after experimental (n = 20) or
      clinical (n = 20) implantation of nails 8 mm and 9 mm in diameter. These
      measurements showed a relatively constant distance between the upper distal
      transverse hole and the anterior aspect of the tibia (average 12.3 mm and only a
      narrow range (7.6 mm). These data were the basis for the development of an aiming
      technique that exploits the relatively constant distance between the distal nail
      hole and the anterior aspect of the tibia. This aiming device is set at a
      distance of 12.3 mm from the anterior cortex, and the fine tuning is finally
      resolved by the use of a "working channel' 10 mm in diameter.

PMID- 9005580
TI  - [HIV infection caused by cold preserved bone transplants].
AB  - We reporting four cases of HIV infection caused by bone allografts from one
      donor. All transplantations were performed between November 1984 and January
      1985. In all, 12 recipients had bone allografts from the HIV-infected donor, 7 of
      whom are now HIV-negative and 4, HIV-positive. One of the patients died a natural
      death in her 10th decade. The donor was not been tested before the grafts were
      harvested, as HIV-antibody detection was not possible at the time (October 1984);
      no HIV-antibody kits had yet been developed. Subsequent testing of the asservated
      serum for HIV antibodies gave a positive result. The chronological course of the
      case is described and the case is discussed in detail.

PMID- 9005581
TI  - [Acute and chronic knee ligament injuries].

PMID- 9005582
TI  - [Bridging an extensive bone defect with cortico-spongious transplants in femoral
      fracture caused by gunshot injury].
AB  - The treatment of a 12-cm bone defect after shotgun fracture of the femur is
      described. Semitubular corticospongious bone grafts from both iliac crests, 6 cm
      long and 0.8 cm wide, were tied into two bundles with an absorbable suture and
      were laid successively into the diaphyseal defect. With another absorbable suture
      the bundles were anchored to the condylar 95-deg plate. Two months later the
      condylar plate was removed and an external fixator placed because of
      inflammation; the bone implants survived. By 18 months after the injury the bone
      defect was cured, no inflammation was present, and the patient was able to walk
      with full weight bearing. Four conditions have to be fulfilled in the treatment
      of an open comminuted fracture with soft tissue defect: thorough necrectomy,
      rigid fixation, bone grafting and improvement of the blood supply by means of a
      microvascular musculocutaneous flap.

PMID- 9005583
TI  - [Bilateral acetabulum fractures of the anterior column and vertebral body
      fracture after alcohol-induced seizure].
AB  - The case of a 54-year-old male with a compression fracture of the T 12 vertebral
      body and a bilateral anterior column fracture of the acetabulum is presented. The
      origin of this rare combination of fractures is explained by the action of the
      patient's own muscle force on bone of very poor quality. The treatment of these
      lesions is comparable to the treatment of similar fractures in bone of normal
      quality.

PMID- 9005584
TI  - [Cytokines and renal injury].
AB  - Cytokines play an important role in most physiological and pathological
      processes. In this note the authors review recent literature data about cytokines
      in mediating renal inflammatory diseases. These molecules are involved in every
      phase of inflammatory injury induce expression of MHC class II and adhesion
      molecules on renal cells, synthesis of chemoattractants; they are also involved
      in leukocyte localization and play a role in the induction of cell proliferation
      and the accumulation of extracellular matrix. The disturbances of the cytokine
      network may lead to inflammatory kidney disease that could be treated by novel
      therapeutic agents like anticytokine antibodies.

PMID- 9005585
TI  - [Alternative treatment of benign prostatic hypertrophy].
AB  - In our study we propose to find an alternative to surgery management of IPB
      usable in DH regime with current instrumentation or with new technology from
      physics. We retrospectively reviewed techniques commonly mentioned in the
      literature to value benefits about cost, comfort, outcomes, and, at the same
      time, we stress disadvantages regarding each of these. TUI is economical, can be
      done in a few minutes, involves minimum bleeding, but can't be utilized in III
      lobe prostate and it doesn't provide material for histological tests. TUBT,
      feasible with light patient sedation, provides not satisfying results.
      Hyperthermia is necessary in selected cases. TULIP must be effected in
      anesthesia, needs complicated and expensive instrumentation, and it isn't
      practicable in III lobe prostate. Urethral stent application is expensive and not
      satisfactory in large size and III lobe prostate. The outcomes we obtained with
      TUI are similar to TUR; TUBT obtains good symptomatological results only in 20%
      of cases at 12 months. Hyperthermia and TULIP obtain an improvement in urinary
      flow rate from 20 to 60% and 50% respectively. Stent application provides good
      results. We think that the most modern, effective and economical alternative to
      the surgery of prostate adenoma is endoscopic surgery in TUI model.

PMID- 9005586
TI  - [Renal agenesis and homolateral seminal vesicle cyst. Case report].
AB  - The authors present a case of renal agenesis and seminal vesicle cyst in a young
      man, diagnosed because of several micturion disorders partially cleared up with
      antibiotic therapy. We discuss about the diagnosis technique which includes
      Ultrasound Scanner, Computed Tomography, Magnetic Resonance and pelvic
      arteriography. Then we describe the surgical approach and finally we discuss
      about embryogenesis.

PMID- 9005587
TI  - [Gangrenous cystitis. Case report].
AB  - A rare case of gangrenous cystitis is described. The questions of the incidence
      of this pathology are discussed, considering its rareness after the antibiotics
      age. The etiology of this disease is probably multifactorial and it is never
      possible to identify a unique cause. The gangrenous cystitis doesn't present with
      any typical symptomatology, out with urinary troubles common to many urologic
      diseases. Surgery is often performed in emergency without a preoperative defined
      diagnosis. Surgical treatment has changed with time from a simple bladder cavity
      draining to the resection of the necrotized bladder wall. In our case a total
      cystectomy with uretero-ileocutaneostomy, in two times, was performed. This
      procedure allowed the patient a good quality of life (1 year of follow-up).

PMID- 9005588
TI  - [Treatment of prostate adenoma with finasteride. Contribution of cases].
AB  - During recent years more and more researchers and clinicians have become
      interested in HPB in order to identify a medical therapy instead of surgery. The
      aim of our study was to find the value of finasteride in HPB therapy. We wanted
      to know if finasteride was able to improve the symptomatology and blood tests of
      patients afflicted with HPB. Every patient was agreed with the course of action
      of the 1991 Paris Urology Congress. All patients were treated with finasteride 5
      mg/die for one year and inspected by prostatic echography and blood tests. The
      results of our study are every interesting and are discussed in the article.

PMID- 9005589
TI  - [Mitomycin-C 30 mg for 12 months versus Mitomycin-C 40 mg for 6 months in the
      prevention of superficial bladder carcinoma G1-G2].
AB  - A total of 60 patients with transitional cell carcinoma of the bladder G1-G2, pTa
      pT1 previously subjected to TUR, were randomised to receive Mitomycin-C (MMC) 30
      mg for 12 months (A group) or Mitomycin-C 40 mg for 6 months (B group). The
      objective of this trial was to compare the prophylactic activity of MMC using two
      different dosages and treatments. All patients were evaluated with cystoscopy.
      Follow-up was of 24 months. The incidence of recurrence in the A group was 40%
      with a recurrence rate of 3.3. In the B group the incidence of recurrence was
      27.6% with a recurrence rate of 2.2. One case of progression was present in the A
      group. The side effects were more frequent in the A group (37% vs 13.3%) and they
      were mainly due to chemocystitis. These data suggest that MMC 40 mg for 6 months
      appears to be superior to MMC 30 mg for 12 months in the prophylaxis of
      superficial bladder carcinoma.

PMID- 9005590
TI  - [Double-blind evaluation of mepartricin 150.000 U (40 mg) compared with placebo
      in benign prostatic hypertrophy].
AB  - The therapeutic efficacy and tolerance of a new 150,000 U (40 mg) formulation of
      mepartricin (to be administered once-a-day in the evening) were evaluated during
      a double-blind study against placebo in 2 groups of uncomplicated BPH patients
      treated for 60 days. The data obtained disclosed a positive pharmaco-therapeutic
      effect of this new formulation coupled with excellent local and systemic
      tolerance. At the end of trial the various objective and subjective parameters
      considered showed marked improvement in the group treated with mepartricin, with
      statistically significant differences from the placebo-treated group. The
      treatment efficacy was judged positive in 74-78% of cases by patients and
      physicians in the mepartricin group and in 36.4% of cases in the placebo group.

PMID- 9005592
TI  - [Golf: a safe sport?].

PMID- 9005591
TI  - [Scene and extreme sports varieties: the injury spectrum is changing].

PMID- 9005593
TI  - [Resorbable reinforcement-plasty].

PMID- 9005594
TI  - [Objectivity in physical therapy evaluation].

PMID- 9005595
TI  - [Report of experiences: personal experience in sports participation. Dominance of
      the over-performance principle in sports].

PMID- 9005596
TI  - [Ligament injury of the ankle joint (I)].

PMID- 9005597
TI  - [Biomechanics of the ligaments of the unstable ankle joint].
AB  - Ligament rupture occurs at the maximum breaking load. During ligament healing,
      contraction and remodeling of the scar is sufficiently advanced at 6 weeks to
      reach 60 to 70% of the initial strength. There is evidence of an early
      improvement in biomechanical properties of repaired ligaments. This advantage,
      however, may not be sustained as, after one year, sutured and unsutured ligaments
      have nearly equal length when measured at rest and comparable failure strength
      when subjected to exercise. Each of the ankle ligaments has a role in stabilizing
      the ankle and/or subtalar joint. Beside of maintaining lateral ankle stability,
      the lateral ankle ligaments have been shown to play a significant role in
      providing rotational ankle stability. This is especially true for the anterior
      talofibular ligament. A loss of this ligament does allow for an increase in foot
      inversion and external rotation of the leg to occur, without any tilting of the
      talus or subtalar gapping. It is this increase in foot inversion which may lead
      to a symptomatic instability. When treating ankle instability, it is therefore
      important for the clinician to take the alteration of hindfoot biomechanics into
      consideration. This is especially the case for any surgical repair of injured
      ankle ligaments. Unphysiological tenodesis procedures should be avoided.

PMID- 9005598
TI  - [Diagnostic imaging of ankle joint instability].
AB  - The value of the available diagnostic methods for the evaluation of the unstable
      ankle joint still is under discussion. This is a result of the increasing
      knowledge of basic biomechanics. It has been demonstrated that ankle instability
      is not restricted to two planes, but can be multidirectional or rotatory. There
      is also a trend to conservative treatment of acute unstable ankle joints. This
      paper presents the actual diagnostic tools for evaluation of the unstable ankle
      joint with regard to their efficiency. Stress views, sonography, MRI and
      arthrography will be discussed.

PMID- 9005599
TI  - [Magnetic resonance tomography (MRI) of ligament injuries of the upper ankle
      joint].
AB  - This paper discusses MR imaging in injuries to the lateral collateral ankle
      ligaments. Based on recent publications and our own results MR imaging may be
      useful for demonstration of ankle ligament tears. However, clinical outcome can
      probably not be predicted by such diagnosis. MR imaging may still be useful in
      certain settings, such as suspected additional trauma to medial ligaments, bone,
      or articular cartilage. In chronic pain MR imaging may be indicated for
      demonstration of articular bodies, occult fractures, significant cartilage
      damage, tendon injuries and dislocations, and soft tissue scars.

PMID- 9005600
TI  - [Arthroscopic findings in the unstable upper ankle joint].
AB  - The purpose of this prospective study was the assessment of the chronic unstable
      ankle joint. With regard to cartilage and ligament lesions this was done
      arthroscopically. 99 consecutive arthroscopies were performed in patients with
      symptomatic chronic ankle instability. There were 67 complete ruptures of the
      anterior talofibular ligament and 45 complete ruptures of the calcaneofibular
      ligament. A complete rupture of the deltoid ligament was found in 6 cases, always
      combined with lesions of the lateral ligaments. Cartilage damage of the talus was
      noted in 51 cases and of the tibial pilon in 12 cases. While all complete lesions
      of the deltoid ligament were associated with talar cartilage damage, this was
      different for lateral ligament lesions. 11/22 ruptures of the talofibular
      ligament were associated with cartilage damage of the talus and 11/22 ruptures
      presented with an intact talar cartilage. Combined ruptures of the talofibular
      and the calcaneofibular ligament were associated with talar cartilage damage in
      21 cases and presented with intact cartilage in 24 cases. This study demonstrated
      a near equal distribution of intact and damaged articular cartilage in the
      presence of lateral ligament lesions indicating that the status of the ligaments
      allows no conclusion with regard to the cartilage. Arthroscopy therefore can give
      essential information about the status of the unstable ankle joint concerning
      operative or conservative treatment.

PMID- 9005601
TI  - [Concomitant injuries after upper ankle joint dislocations].
AB  - Functional treatment with the Air Stirrup Ankle Brace recommended by C. N. Stover
      in 1979 can reduce pathological inversion of the ankle joint. In our
      retrospective study of 109 patients treated by this kind of ankle brace we found
      96 patients (88%) with excellent results. Only 13 patients (12%) reported
      moderate to good results. To detect and characterize their painful conditions of
      ankles we did a clinical, radiological and MRI-Investigation. In only 2 cases we
      found a moderate instability after clinical investigation, anterior stress
      roentgenogram and talar tilt. By using the MRI-investigation 1.0 Tesla with a 512
      x 360 Matrix we could find 10 cases with osteochondral lesions of the ankle. In 7
      cases there was separated ossicle in the fibulotalar joint, in 1 case we detected
      a fracture of the processus anterior tali, in another case we could see a
      posttraumatic lesion of the talus and calcaneus with bone bruise and at least one
      osteochondral fracture of the distal tibia. The capability of the MRI to detect
      particularly osteo-chondral lesions of the talus and the tibiofibular joint was
      shown in 10 of 13 cases. Therefore we recommend to do an MRI-investigation on all
      patients after ankle sprain if there are painful conditions within the ankle
      after conservative treatment.

PMID- 9005602
TI  - [Osteolysis of the lateral clavicle after Tossy II injury in ice hockey players].
AB  - Injuries of the acromioclavicular joint in hockey mainly occur after trauma
      directly to the shoulder joint. E.g. at a fall against the border, onto the
      ground or in case of a body check. Tossy-III-lesions lead directly to surgery
      meanwhile type Tossy-II-lesions are mainly treated conservatively. Despite
      healing of the acromioclavicular ligaments often acromioclavicular joint pain
      remains despite conservative treatment because of discuss lesions or a osteolysis
      of the lateral end of the clavicle. The resection of the lateral end of the
      clavicle with certain pain relief, very good functional results and quick full
      level participation in hockey has been shown as the method of choice in our
      patients.

PMID- 9005603
TI  - [The possibilities for real improvement in the prognosis and quality of life of
      patients with ischemic heart disease].

PMID- 9005604
TI  - [The current concept of the use of calcium antagonists in cardiology. Resolution
      of the Academic Council of the A. L. Miasnikov Research Institute of Cardiology
      of the KNTs of the Russian Academy of Medical Sciences].

PMID- 9005605
TI  - [The indices of the fibrinolysis, blood coagulation and lipid transport systems
      in hypertension patients].
AB  - Lipid spectrum, basal insulin concentration, the activity of coagulation factor
      VII and inhibitor of plasminogen tissue activator, content of plasminogen tissue
      activator antigen were assessed in 54 hypertensive patients with left ventricular
      hypertrophy (mean age 48.9 +/- 0.9 years, mean duration of the disease 15.7 +/-
      1.1 years) after discontinuation of hypotensive therapy. A correlation was found
      between a rise in thrombogenic, atherogenic and a fall in fibrinolytic potential
      of blood. These findings suggest an essential role of insulin in regulation of
      thrombogenesis and fibrinolysis in hypertensive patients.

PMID- 9005606
TI  - [Factors affecting left ventricular diastolic function in hypertension patients].

PMID- 9005607
TI  - [The clinical aspect of the joint use of magnetic resonance tomography of the
      brain and magnetic resonance angiography of the extra- and intracranial arteries
      in patients with arterial hypertension].
AB  - NMR tomography (NMRT) of the brain and NMR angiography (NMRA) of the extra- and
      intracranial arteries were performed on the unit Magnetom 63 SP (1.5 T) Siemens
      in 13 healthy controls and 87 patients with cerebrovascular diseases initiated by
      arterial hypertension and atherosclerosis of major cerebral arteries. NMRA image
      of arterial impairment comprise curved extracranial arteries. NMRT picture of the
      brain was changed (extension of liquor spaces, small hyperintensive foci in the
      white matter) in mild and moderate hypertension. Frequency of these phenomena and
      their severity increase with growing severity of the disease reaching maximum in
      malignant hypertension. In atherosclerosis of the major cerebral arteries NMRT
      often detected strokes, for the most part ischemic. A direct relationship between
      the degree of arterial stenosis and incidence of the strokes was not found.

PMID- 9005608
TI  - [Nifedipine in ischemic heart disease: a ban on its use or a differential
      approach to therapy?].
AB  - Pharmacological properties of nifedipine are compared to those of other calcium
      antagonists. The author disagrees with those investigators who make conclusions
      on nifedipine inadequacy in any forms of ischemic heart disease emphasizing its
      negative effect on the survival. The author argues that negative effects of
      nifedipine are proved in unstable angina pectoris and acute myocardial infarction
      whereas in stable angina of effort its effectiveness may be superior to other
      antianginal drugs. Such unwanted events as developing tolerance to nifedipine in
      its long-term use, withdrawal syndrome in its sudden discontinuation are not
      inevitable. It is thought valid to prescribe nifedipine in stable ischemic heart
      disease.

PMID- 9005609
TI  - [The prolonged-action form of Lomir (isradipine) in the treatment of mild and
      moderate essential hypertension].
AB  - 24-hour monitoring of arterial pressure has been performed outpatiently in 20
      subjects with mild or moderate essential hypertension using portable system Space
      Labs 90207. The design of the study implied 2 weeks of observation without any
      treatment followed by a 4-week course of lomir SRO-5 plus a 2-week course of
      lomir administration in a double dose. Control examination was performed at the
      end of each period. It was established that a 4-week lomir course results in a
      lowering of systolic and diastolic pressure by 8.4 + -2.1 and 6.9 + -1.3 mm Hg,
      respectively. Double-dose lomir was also effective: a fall in both systolic and
      diastolic pressure by 15.6 + -3.2 and 8.1 + -1.8 mm Hg, respectively, was
      achieved.

PMID- 9005610
TI  - [The correlations of lipid peroxidation, antioxidant protection and
      microrheological disorders in the development of IHD].
AB  - Lipid peroxidation, antioxidant defense and microrheological properties of blood
      were determined, correlated and compared with clinico-hemodynamic indices in
      patients with ischemic heart disease (IHD). It is shown that products of lipid
      peroxidation modify structure and function of red cells and platelets in IHD. A
      regulatory role of the antioxidant system in metabolism of lipoperoxides and
      peroxide damage to blood cells in IHD is shown. A pathogenetic implication of
      correlated changes in the systems of lipid peroxidation and antioxidant defense,
      microrheological properties of blood in formation of clinical course of IHD is
      revealed.

PMID- 9005611
TI  - [Silent myocardial ischemia in patients with different clinical forms of IHD].
AB  - 70 IHD patients underwent ambulatory Holter ECG monitoring two times. Out of 357
      episodes of transitory ischemia registered in the course of exercise and
      presenting primarily as ST depression the proportion of silent episodes reached
      75.6%. The number of episodes, their duration and mean value of ST depression
      were significantly greater in subjects 1 year after myocardial infarction. These
      patients more frequently developed ventricular arrhythmia and had ejection
      fraction below 50%. The findings evidence a significant clinical value of silent
      myocardial ischemia. It may serve a predictor of repeated acute coronary
      accidents in postmyocardial infarction patients.

PMID- 9005612
TI  - [The prediction of the probability of the development of myocardial infarct by
      genetic and phenotypic markers].
AB  - The study was made of marker distribution of 17 hereditary polymorphism systems
      in 493 patients with myocardial infarction (MI) and 422 healthy subjects. The
      prognostic system for determination of predisposition or resistance to MI
      development has been designed in accordance with marker occurrence in the
      patients and healthy subjects basing on Bayer's method. When the sum of the
      prognostic ratios of all the markers is +5 scores and more there is a high risk
      of MI, when this sum is -6 scores and less the resistance to its genesis is
      predicted. The proposed prognostic system makes it possible to predict
      predisposition to myocardial infarction at an early age and, therefore, to take
      preventive measures.

PMID- 9005613
TI  - [The use of the antioxidant trimetazidine (Preductal) in the combined therapy of
      acute myocardial infarct].
AB  - 86 patients with acute transmural and macrofocal myocardial infarction received
      combined treatment which included standard therapy (thrombolytic drugs, beta
      blockers, APP inhibitors, nitrates, aspirin) and antioxidant trimetasidine. The
      addition of the latter was beneficial: the size of the myocardial lesion was
      limited, electrical instability of the heart attenuated, early dilatation of the
      left heart prevented.

PMID- 9005614
TI  - [The discussion heating up on the lack of safety in using calcium antagonists and
      in particular the dihydropyridine derivative nifedipine].

PMID- 9005615
TI  - [The characteristics of the adaptation to the hypoxic conditions at a low
      altitude health resort in IHD patients after an aortocoronary bypass].
AB  - Adaptation to hypoxia is an important training factor for patients with ischemic
      heart disease subjected to aortocoronary shunting. In the conditions of low
      maintain health resort this adaptation lasts for 3-5 days and most of the
      patients avoid complications. Pathological reactions occur in patients with
      inadequate reserves of the coronary system, having essential hypertension, severe
      concomitant diseases, in those who arrived at health resort earlier than 5 months
      after aortocoronary shunting.

PMID- 9005616
TI  - [The quality of life and survival of patients with an implanted pacemaker (the
      results of long-term observation)].
AB  - 110 patients with implanted pacemaker were followed up for 1 to 10 years until a
      complete atrioventricular block. Permanent pacemaking is effective as it
      eliminates or reduces many symptoms, prolongs active life, improves quality of
      life in 81.4% of patients. Some of the patients were able to resume work.

PMID- 9005617
TI  - [The significance of subclinical forms of aortic regurgitation detected during
      Doppler echocardiography].
AB  - To clarify prognosis and therapeutic approaches to mild and moderate aortal
      regurgitations (AR) silent clinically but identified at Doppler echocardiography,
      the authors followed up for 3 years 35 AR patients aged 22-73 years. AR and left
      ventricular function (LVF) were measured on echocardiograph Sonos-1000 (Hewlett
      Packard, USA). Mild AR had a favourable prognosis, LVF remained intact, no
      symptoms of AR occurred. Moderate AR manifested with a trend to increased end
      diastolic and stroke volume of the left ventricle. Aortal failure progressed
      rapidly in 4 patients with moderate AR in active valvular inflammation and
      progressed slowly in 3 patients with atherosclerosis and dilatation of the aortic
      root. It is concluded that patients with moderate AR detected at echocardiography
      should be followed up to control unfavourable developments.

PMID- 9005618
TI  - [Endomyocardial fibrosis (its clinico-echocardiographic characteristics)].
AB  - To compare clinical and echocardiographic features in patients with restrictive
      cardiomyopathy (RCMP), 15 patients (9 males and 6 females, mean age 34.93 +/-
      1.03 years, duration of the disease 9 +/- 4.2 months) were examined using
      complete echocardiographic and doppler echocardiographic investigation in impulse
      regimen. Endomyocardial fibrosis was not obvious clinically, but should be
      suspected in dyspnea upon a weak exercise, undue fatiguability, tachycardia in
      normal arterial pressure and size of the heart. Echocardiographic indications, on
      the contrary, were rather specific. Endomyocardial fibrosis is characterized by
      diminished ventricular cavities, thickening of the endocardium and subvalvular
      structures, changed shape of ventricular cavity, echo-CG signs of passive
      pulmonary hypertension, diastolic dysfunction of the left and right ventricles.

PMID- 9005619
TI  - [Generational continuity. On the 150th anniversary of the formation of the
      Hospital Therapeutic Clinic of the I. M. Sechenov Moscow Medical Academy].

PMID- 9005620
TI  - [The physiology of defense. On the border between health and disease].

PMID- 9005621
TI  - [A. L. Miasnikov and the Hospital Therapeutic Clinic].

PMID- 9005622
TI  - [What I know about A. L. Miasnikov (reminiscences on the anniversary of the
      Department of Hospital Therapy of the I Moscow Medical Institute)].

PMID- 9005623
TI  - [The Hospital Therapeutic Clinic of the 50s and 60s through the eyes of a young
      physician].

PMID- 9005624
TI  - [The clinical pharmacology and efficacy of statins].

PMID- 9005625
TI  - [A case of a combination of systemic scleroderma with diffuse eosinophilic
      fasciitis].

PMID- 9005627
TI  - [Lameness in a dog following gunshot wound; case report and management protocol].
AB  - The clinical signs and surgical treatment of a 3-year old German wirehair Pointer
      with chronic intermittent lameness due to a gunshot injury are presented. In
      addition to routine radiography, ultrasound investigation and positive contrast
      arthrography of the radiocarpal joint showed that a bullet was located in the
      lateropalmar part of the radiocarpal joint cavity. Surgical removal of the bullet
      led to complete clinical recovery. A diagnostic and therapeutic protocol is
      presented for dogs and cats with gunshot injuries.

PMID- 9005626
TI  - [A case of a combined course of gout and rheumatism].

PMID- 9005629
TI  - [80 percent of infections originate in the kitchen. 'Everything is everywhere,
      man regulates'. Interview by S. Deleu and W. Sybesma].

PMID- 9005628
TI  - [3rd World Congress Veterinary Dermatology].

PMID- 9005630
TI  - [Career planning and future expectations of veterinarians. Women are too modest
      about their abilities].

PMID- 9005631
TI  - [The molecular mechanisms of the somatic effects of irradiation recorded in
      plants from the 10-km area around the Chernobyl Atomic Electric Power Station].
AB  - The comparative analysis of some biochemical features of the Picea abies
      morphologically abnormal organs and the control tissues was made. The methods of
      restriction analysis. Southern hybridization of DNA and protein electrophoresis
      were used. The differences detected in protein context and in DNA structure
      indicated the changes in genomes of experimental plants. These changes may be
      caused by chronic irradiation in low doses.

PMID- 9005632
TI  - [Chromosome aberrations in different tissues of the murine rodents and amphibians
      from radionuclide-contaminated regions of Belarus].
AB  - Cytogenetic investigations of amphibian and rodent populations from the
      contaminated by radionuclides regions of Belarus was conducted. A significant
      increase in the levels of cytogenetic anomalies in bone marrow cells and
      intestinal epithelium of amphibians and rodents, the levels of alveolar
      macrophages of rodents, and micronuclei in peripheral blood erythrocytes of
      amphibians was revealed. Presence of chromosome type aberrations indicates that
      radiation as a mutagenic factor was involved. No strict relationship between the
      levels of contamination of the area and levels of cytogenetic anomalies was
      found.

PMID- 9005633
TI  - [The heterogeneity of the cytogenetic variability in the bone marrow cells of
      laboratory and wild rodents in the exclusion zone of the Chernobyl Atomic
      Electric Power Station].
AB  - Analysis of the characters of cytogenetic variabilities and correlative
      interrelations between them revealed the group specificities of karyotype
      instability in bone marrow cells of some lines of laboratory and of wild mice
      under the conditions of increased radionuclide pollution in the Chernobyl zone.
      The complex correlative interrelations between the frequencies of cytogenetic
      anomalies and the character of cell division (the number of metaphases,
      binucleated leukocytes per 1000 cells) were observed. The obtained data indicate
      the stimulatory influence of chronic low doses of ionizing radiation on the
      manifestation of spontaneous mutagenesis, which has own genotype specific
      characteristics.

PMID- 9005634
TI  - [The adaptation of natural plant populations to chronic irradiation due to the
      accident at the Chernobyl Atomic Electric Power Station].
AB  - The effects of plant seed additional irradiation in the 8th and 9th post
      Chernobyl reproduction were studied by the test "chromosome aberrations in
      seedling root meristem". In most of plant species investigated, seeds developed
      in the radiocontaminated zone were more radiosensitive than those from the
      "clean" zone. This fact shows the lack of adaptation to chronic irradiation and
      the availability of the potential genetic lesions that are realized into
      mutations under the influence of extreme factors. The effects of seed additional
      irradiation in some plant species indicate an increase in plant radioresistance.

PMID- 9005635
TI  - [The dynamic mutability of the somatic and germ cells of animals inhabiting
      regions of radioactive fallout].
AB  - Many generations (1-18) of natural populations of small mammals that inhabited in
      1986-1991 areas contaminated by radionuclides, had increased levels of the
      mutations in somatic cells and gametes. The high frequency of chromosome
      aberrations in somatic cells of young carps from contaminated ponds was detected
      in 1988-1992. Radiosensitivity of hereditary structures of animal somatic cells
      and gametes was increased in subsequent generations as compared with generations
      that lived in 1986-1988.

PMID- 9005636
TI  - [The genetic monitoring of the house mouse population from areas contaminated by
      radionuclides as a result of the accident at the Chernobyl Atomic Electric Power
      Station].
AB  - In 1986-1994, genetic effects of radiation on males of wild mice caught in areas
      of radioactive contamination after the Chernobyl reactor accident were studied.
      The gamma-radiation dose rates on the soil surface in the areas varied from 0,02
      to 200 mR/h. The frequency of reciprocal translocations in mouse spermatocytes
      was relatively low and increased linearly with increasing of the dose rate. The
      levels of recessive lethal mutations in mouse populations did not depend on the
      radiation dose rate in the areas and decreased with a time.

PMID- 9005637
TI  - [The dynamics of the allele variants of biochemical markers in generations of
      cattle in the exclusion zone of the Chernobyl Atomic Electric Power Station].
AB  - Analysis of the heritability of allelic variants of polymorphous genetic
      biochemical systems in the cattle groups, reproduced in conditions of increased
      radionuclide pollution in exclusion zone of the Chernobyl AES was carried out.
      The disturbances of equal probability of the heritability for different allelic
      variants in some cattle group were revealed. It was supposed, that the appearance
      of the disturbances may take part in changeabilities of different gene pools
      under the conditions of ecological stresses. Possible mechanisms of this
      phenomenon were discussed.

PMID- 9005638
TI  - [Erythron system function in adults subjected to radiation exposure as a result
      of the Chernobyl accident].
AB  - The morphofunctional state of hemopoiesis in patients who suffered from the
      Chernobyl accident was investigated. The activation of proliferative activity of
      erythroid progenitor cells simultaneously with a decrease in the resistance of
      erythrocytes and an increase in the levels of methemoglobin, HbF, and an increase
      in the number of HbF-containing cells in peripheral blood were detected. Main
      trends in the development of adaptative processes in the erythron system as a
      response to affect of low doses of radiation were determined on cellular and
      molecular levels.

PMID- 9005639
TI  - [Disorders in the synchronism of homologous chromosome condensation in women with
      a predisposed familial anamnesis].
AB  - The automatic program for cytogenetic investigations of differentially stained
      chromosomes was developed and used in practice. The high sensitive criterium for
      automatic selection of persons who has the early symptoms of karyotype
      instability was created. We performed the cytogenetic analysis in the women who
      has a burdened obstetric anamnesis after the exposure to radiation in Pripyat, in
      the group of healthy women from Kiev, and began the creation of computerized data
      bank of differentially stained human chromosomes.

PMID- 9005640
TI  - [The latest achievements of radiation cytogenetics in connection with the
      discovery of the method for the fluorescence hybridization in situ of the
      metaphase chromosomes of man and experimental animals using DNA probes (FISH)].
AB  - This review describes the development of novel promising molecular cytogenetic
      method--fluorescence in situ hybridization with human and animal whole-chromosome
      probes (F I S H). It summarizes the application of this technology in fundamental
      and applied fields of radiation cytogenetics and emphasizes the important role of
      FISH for biological dosimetry of human exposure to ionizing radiation.

PMID- 9005642
TI  - [Populations of higher plants found in the area of influence of the Semipalatinsk
      proving grounds].
AB  - Population of Scotch pine and crested wheat grass growing on the territories of
      Semipalatinsk testing ground and contaminated during the traits of nuclear
      weapon, and in the control region differ by a number of genetic and cytogenetic
      trials. Besides, it is evident that the investigation of the nature of genetic
      anomalies and their association with radiation factors in the problem more
      complicated than merely to recognize the fact of their availability. This calls
      for further investigations.

PMID- 9005641
TI  - [Genetic or ecogenetic consequences of the Chernobyl accident? (facts and
      hypotheses)].
AB  - The results of investigations indicated the necessity of genetic monitoring in
      population using the data of family examination in medical genetic centres.
      Indices of the frequency of developmental abnormalities in newborns are not
      suitable for monitoring because they do not permit to differentiate between new
      mutations and inherited ones. The dissemination of these abnormalities among
      newborns in Kiev mostly coincides with the same index in other European regions
      and is lower than in Canada and West Australia. According to the data of Kiev
      regional medical genetics centre, about 80% of developmental abnormalities occur
      as a result of inherited mutations but not new ones. Under the conditions of
      environmental pollution, ecogenetic consequences assume a new importance.

PMID- 9005643
TI  - [Changes in the size and morphology of cells under the influence of bacterial
      ribonuclease].
AB  - It has been found that a single interperitoneal injection of mice with NKLy
      ascite lympholeukosis cells and Bacillus intermedius RNAse or its derivative,
      obtained in result of activation of the active centre, on histidine induces an
      increase in size of cells cultured in vivo, the number of morphological changes
      in the cell cytoplasm, cell nucleus and, to a large extend, in the cell surface.
      A share of 2-3 nucleated cells increases as a result of both an incomplete
      mitosis and cell fusion. These changes do not depend on catalytic activity of
      RNAse. 24 hours following RNAse injection, both dimensions and morphology of the
      majority of cells returned to the norm. The trigger mechanism resulting in all
      the above mentioned changes is thought to be RNAse bringing about nonspecific
      irritation (reversible damage) of cells.

PMID- 9005644
TI  - [The characteristics of cell lines used in biotechnology].
AB  - Cultural and biological characteristics of three suspension continuous cell
      lines, BHK-21/C, PSGK and PTP, were studied aimed to apply them in future to
      research and production purposes. Cell generation term and growth conditions were
      determined. A comparative karyologic analysis of a new trophovariant of BHK-21/C
      cells and an initial cell line was conducted.

PMID- 9005645
TI  - [The histogenesis of embryonic neocortical allografts in rats under the action of
      cyclosporine A].
AB  - By means of morphological methods, a study was made of effects of cyclosporin A
      (Cs A) on developmental dynamics in 15 day old embryo neocortex transplanted into
      the rat brain. It is shown that Cs A exerts no cytotoxic or cytostatic effects on
      grafting cells. Differentiation of grafting neuroepithelial cells into
      neuroblasts, young neurons and neurons in transplants of Cs A-treated rats and
      control transplants took place at the same time. Mitotic activity of grafting
      neuroepithelial cells was lower than in developing neocortex in situ;
      pathological mitotic forms have been described.

PMID- 9005646
TI  - [The role of the actin cytoskeleton in cell transition through the middle of the
      G1 phase of the mitotic cycle].
AB  - The influence of dihydrocylochalasin B (H2CB), which selectively disrupts the
      actin cytoskeleton structure, on G1 phase progression after stimulation of
      quiescent Swiss 3T3 cells by epidermal growth factor (EGF) was investigated. H2CB
      was added to the culture medium (10 mg/ml) for different periods of time after
      cell cycle induction by EGF (10 ng/ml). Efficiency of mitogenic stimulation was
      estimated by 14C-thymidine uptake 21-23 h after EGF addition. It is shown that
      the main actin-mediated step is in the middle of G1, from 8 to 12 h after
      stimulation. Disorganization of actin cytoskeleton structure only during this
      time led to complete and irreversible block of cell entry into the S phase. On
      the contrary, the same effect of H2CB during the early period of G1 (first 6 h)
      led to the increase in 14C-thymidine incorporation in DNA. The specificity of
      actin-dependent period was proven in experiments with another inhibitor of cell
      proliferation--dancylcadaverine, whose effect was revealed at the earlier time--4
      6 h after cell stimulation. Inhibition of protein synthesis during actin
      dependent period (8-12 h) led to the same block of cell progression through G1 as
      it was seen after actin structure disruption. These data suggest that actin
      dependent block is associated with the appearance and functioning of such
      specific regulators of G1 as cyclins (D, E) and their complexes with Cdk's (G1
      kinases) which phosphorylate Rb protein (p1 10) associated with transcription
      factors E2F.

PMID- 9005647
TI  - [The influence of C-reactive protein and its subunits on the cytotoxic effect of
      tumor necrosis factor-alpha in relation to L929 fibroblasts].
AB  - A study was made of the ability of purified human C-reactive protein (CRP) in
      pentameric (pCRP) and subunit (sCRP) form to induce the production of tumour
      necrosis factor alpha (TNF-alpha) in macrophage-like cell line P388D1, as well as
      the combined effects of CRP and recombinant human TNF-alpha on the proliferation
      of L929 cell line. Both pCRP and sCRP induced TNF production by P388D1 cells,
      pCRP was inhibitory per se for L929 cells, while sCRP was not, when present in
      cultures for 72 h without actinomycin D (AD). In the presence of AD, sCRP was
      inhibitory as well, even when the period of incubation was reduced to 18 h. The
      presence in CRP of melittin-like sequence known to be responsible for the
      activation of cellular phospholipases is shown herein. Together with literature
      data, indication that CRP does influence the catalytic activity of purified
      phospholipase D, suggests that CRP exerts effect on P388D1 and L929 cells via
      regulation of cell phospholipases. The results also indicate that TNF effects in
      vivo can be modulated in different ways by conformational variants of CRP, whose
      occurrence and ratio depend on a phase of inflammatory reaction.

PMID- 9005649
TI  - [The dynamic intracellular distribution of nucleolar protein B23 in the
      interphase and mitotic cells of mammalian cultures].
AB  - Using monoclonal antibodies against B23 (Ochs et al., 1983) and indirect
      immunofluorescence of cells exposed to different conditions of fixation,
      distribution of B23 in HeLa (human) PtK1 (rat kangaroo) and PK (pig) cells was
      studied at interphase and mitosis. In different cells B23 is distributed in a
      similar manner. At interphase it is located mainly within nucleoli. When cells
      enter mitosis (at prophase), B23 translocates from nucleoli to the nucleoplasm,
      and after breakdown of the nuclear envelope at prometaphase-to the cytoplasm to
      remain there till the end of telophase. As extraction buffers are applied to
      remove soluble cytoplasmic proteins. B23 is clearly seen on the surface of
      chromosomes. This unequivocally indicates that B23 is a "chromosomal passenger
      protein" (Earnshaw, Barnet, 1991). At telophase, the formation of numerous
      prenucleolar bodies on the surface of chromosomes starts. A long-term incubation
      of cells with actinomycin D prevents from the appearance of B23 around
      chromosomes and within prenucleolar bodies.

PMID- 9005648
TI  - [The effect of membrane-transport inhibitors on the vacuolization of skeletal
      muscle fibers induced by glycerin removal from them].
AB  - Effects of inhibitors of volume regulation on reversible vacuolation of skeletal
      muscle transverse sarcotubules have been studied. The drugs include inhibitors of
      sodium pump (ouabain), electrodiffusion Cl- and K+ channels (SITS, DIDS, niflumic
      acid, Ba2+), anion-cation cotransport and antiport (bumetanide, furosimide,
      amiloride), calcium channels (verapamil, nifedipine), stretch-activated ion
      channels (Gd3+) and water channels (Hg2+). The drugs were used at concentrations
      usually inhibiting the regulatory volume response in nonmuscle cells. The
      vacuolation-devacuolation cycles of frog muscle fibers were observed under the
      light microscope during efflux and entry of glycerol (90 mM). Neither of used
      inhibitors produced any noticeable effect on development and disappearance of
      vacuolation. A conclusion is made that development of vacuoles from the T-system
      during glycerol removal is not associated with activation of ion transport
      pathways that leads to regulatory volume decrease or increase in other cell
      types. The mechanisms of T-tubule vacuolation are discussed.

PMID- 9005650
TI  - [Vladimir Iakovlevich Aleksandrov (1906-195)].

PMID- 9005652
TI  - [Inactivation of yeast pyruvate decarboxylase in the presence of substrate and
      quinone electron acceptors].
AB  - The rate constants of paracatalytic inactivation of pyruvate decarboxylase in the
      presence of 1,4-naphthoquinones and 1,4-benzoquinones are determined by redox
      potentials of the oxidant. The logarithm of k2 depends hyperbolically on the
      redox potential of quinone E0(Q/Q-.) with the coefficient of proportionality
      which approximates 8.4, The absence of considerable deviations in this
      correlation for the oxidants of different structures with closed values Eo(Q/Q-.)
      indicates that the enzyme produces no additional steric barrier.

PMID- 9005653
TI  - [The effect of nicotinamide on the enzymatic activity of the antioxidant defense
      in experimental diabetes].
AB  - Experiments on rats with experimental streptosotocin-induced diabetes have shown
      intensification of the lipid peroxidation processes and reduction of activity of
      antioxidant defensive enzymes. The content of G-SH and glutathione peroxidase
      activity has decreased in comparison with the normal rate by 69% and 28%,
      respectively. Glutathione reductase activity has risen by 20%. Activity of the
      antioxidant enzymes (superoxide dismutase, catalase) has reduced and the amount
      of the final product of lipid peroxidation, MDA has increased. Injection of
      nicotinamide to diabetic rats (200 mg/1 kg of weight) for 14 days normalized
      activity of the antioxidant enzyme system and the content of the lipid
      peroxidation products.

PMID- 9005651
TI  - [Protein and RNA biosynthesis in the nuclei of the thymus cells of piglets with
      antenatal hypotrophy].
AB  - The nuclear protein synthesis and DNA-dependent RNA polymerase activity were
      found to be different in the thymus of normal and hypotrophic animals. Under the
      influence of aethonium preparation from the class of quartered ammonium compounds
      the protein-synthesizing apparatus and DNA-dependent RNA polymerase activity of
      the thymus cell nuclei of hypotrophics were activated almost up to the level of
      normally developing pigs.

PMID- 9005655
TI  - [The formation of supramolecular complexes as the pathway in the regulation of
      glycolytic enzyme activity].
AB  - Information on the regulation of glycolytic enzyme properties by means of their
      reversible interaction with structural elements of the cell: myofibrillar and
      cytoskeletal proteins and with different kinds of membranes is generalized. The
      problem on the possible formation of complexes of glycolytic enzymes is
      discussed.

PMID- 9005654
TI  - [Ca2+ ion transport in the sarcoplasmic reticulum of the gastrocnemius muscles of
      white rats under treatment of the sciatic nerve with a colchicine solution].
AB  - In different time after application of 12.5 microM colchicine-inhibitor of
      exoplasmic current to the ischiadicus the quantity of amino acid residues of
      methionine and cysteine in the sarcoplasmic reticulum decreases, its protein
      content changes. The Ca(2+)-ATPase activity increases on the 3d day after
      colchicine application and decreases on the 14th day. Analogical changes are
      observed in the capacity of the sarcoplasmic reticulum to transport calcium ions,
      the Michaelis constant in this case being stable. Passive outflow of Ca2+ from
      the sarcoplasmic reticulum vesicules changes in such a way: the Michaelis
      constant decreases with a simultaneous increase in the maximal velocity after 14
      and 28 days of colchicine application.

PMID- 9005656
TI  - [The dynamic biosynthesis of nicotinamide coenzymes from nicotinamide and
      nicotinic acid in rat tissues].
AB  - Dynamics of nicotinamide coenzyme biosynthesis in rat tissues has been studied
      systematically with previous injection of two main precursors nicotinic acid and
      nicotinamide (50 mg/100 g of weight. This process is characterized by exact
      tissue specificity. As a precursor of NAD-biosynthesis nicotinamide was used more
      intensively in the liver and brain tissues. In the mucous tissue of intestine
      nicotinic acid was utilized more intensively. An increase in the NADP+ content in
      tissues with high level of NAD+ biosynthesis is limited as a result of
      competition between these two processes for the intracellular ATP level.

PMID- 9005657
TI  - [The neural activity of thiamine: facts and hypotheses].
AB  - A review of some experimental results as to identification of the specific role
      of thiamine in functioning of nerve cells is presented. Failure to attribute high
      neuroactivity of thiamine considering only its known biochemical function as a
      coenzyme precursor of some key Enzymes of the carbohydrate metabolism has formed
      conceptions existence of non-coenzyme functions in this vitamin which are
      realized in nerve cells. The Investigation of this thiamine function has been
      developing mainly in two principal directions the study of participation of
      biologically active thiamine derivatives is functioning of the excited membrane
      ion channels and the study of their role in the synthesis and metabolism of
      acetylcholine. Taking into account analysis of their own data and those available
      in literature, the authors formulate a hypothesis which attributes high
      neuroactivity of thiamine not to the existence of a certain function in the nerve
      cells new for this vitamin but only to the peculiarities of the structure
      functional organization of the cells the existence of excited membrane, and
      interdependence between the cellular metabolism and transport of loss via the
      membrane, which underlies regulation of the synthesis, release, capture and
      catabolism of neurotransmitters.

PMID- 9005658
TI  - [The metabolism of [2-(14)C] glycine in rat tissues in vivo].
AB  - It is found that two hours after intraperitoneal injection of [2-(14)C] glycine
      to rats its higher amount (83.6%) is used in the protein synthesis and 16.4% is
      catabolized. The carbonic chain of the amino acid is used to the greater extent
      in the synthesis of lipids than in the oxidation and glucogenesis. Radioactivity
      of the proteins in the investigated organs and tissues of rats varies within L7
      50.6 thou. DPM per 100 mg of wet tissue and decreases in a series: small
      intestine mucosa, kidneys, liver, stomach mucosa, heart, lungs, cardiac muscle,
      skin, skeletal muscle, adipose tissue, brain. Radioactivity of lipids is within
      the limits of 0.2-5.1 thou. DPM per 100 mg of wet tissue 11.7-81.6% of protein
      radioactivity) and decreases in a series: liver, adipose tissue, kidneys, lungs,
      cardiac muscle, stomach mucosa, skin, skeletal muscle, brain. The total
      radioactivity of glucose+glycogen varies within 0.05-0.34 thou. DPM per 100 mg of
      wet tissue (0.8-10.7% of protein radioactivity) and decreases is a series:
      kidneys, liver, brain, skeletal muscle.

PMID- 9005659
TI  - [The effect of 2,4-dinitrophenol and glucose on the utilization of succinate,
      lactate, pyruvate and formate by Escherichia coli K12].
AB  - The effect of protonophore 2,4-dinitrophenol (5-25 microM) in lithium chloride
      acidic medium (pH 4.5) on utilization of acidic energetic substrates was studied
      in the presence and absence of glucose. The rate of succinate, lactate and
      pyruvate utilization by AB 1157 strains was two times lower, than by the KS 400
      strain. Isomolar glucose concentration (0.5 mM) decreased the utilization rate of
      succinate by 60% pyruvate by 30% the AB 1157 strain being much more sensitive
      than the KS 400 strain both to the action of glucose and to the reaction to
      glucose and 2,4-dinitrophenol. Acidification of the medium by bacteria has been
      observed, which shows changes in energy metabolism (glycolysis takes place
      instead of oxidation of substrates) under conditions of intensive aeration. The
      results obtain permit assuming that the AB 1157 strain has a certain defect of
      the membrane which causes increased proton conduction.

PMID- 9005660
TI  - [The role of the thrombocyte-activating factor in inhibiting Na+,K(+)-ATPase in
      different tissues after ischemia and reperfusion of the small intestine].
AB  - Activity of transport Na+, K(+)-ATP-ase has been studied both in the ischemia
      affected proximal section of the small intestine and in tissues which did not
      endure ischemia (the brain, renal cortex and the distal part of the small
      intestine) in dynamics 5, 30 and 60 min, after reperfusion of the ischemized
      small intestine of rats. It is shown that after 30 min-long ischemia of the small
      intestine, the Na+, K(+)-ATP-ase activity is inhibited in all the tissues
      mentioned. Maximal inhibition of the enzyme activity after 30 min long
      reperfusion is 74, 34, 94 and 58% for the brain, renal cortex, proximal and
      distal sections of the small intestine, respectively. It has been found that the
      blood serum from ischemized rats also exerts an inhibitory effect on the enzyme
      activity. Application of inhibitor of the thrombocyte-activating factor (TAF)
      BN52021 has permitted demonstrating its role in the protecting effect under
      conditions of Na+, K(+)-ATP-ase inhibition in the post-Ischemic period and
      inhibitory effect of the blood serum from ischemized rats on the enzyme activity.
      A conclusion is made that the TAF participated in the inhibitory effect of Na+,
      K(+)-ATP-ase activity in different tissues after ischemia of the small intestine
      of rats.

PMID- 9005661
TI  - [The amino acid composition of the antigenic structures of the human heart
      conduction system].
AB  - Amino acid composition of proteins from antigen preparations of the human heart
      conduction system has been studied. Differences in amino acid composition and
      relative affinity of the structure of two groups were found: between the sinus
      and atrioventricular nodes, the His bundle and contractile myocardium.

PMID- 9005662
TI  - [The thermally induced transformation of the protein-detergent complexes of the
      Na+,K(+)-ATPase catalytic subunits of the kidneys and brain in PAG
      electrophoresis].
AB  - Electrophoretic properties of the protein bands of Na+, K(+)-ATPase catalytic
      subunits of the kidney and brain have been comparatively studied for some types
      of animals after heat treatment of the preparations in the presence of DS-Na. The
      diffuse protein zone with lower electrophoretic mobility after heat-induced
      conformational transformation of alpha appears on gels parallel with protein band
      alpha II which is typical of this process. The prolonged heat treatment causes
      more rapid electrophoretic degradation of the alpha-isoform of the Na+, K(+)
      ATPase catalytic subunit of the brain in comparison with alpha +. The results of
      the investigations are discussed in the aspect of existence of heat-induced
      transformation of the protein-detergent complexes of catalytic subunits of the
      enzyme.

PMID- 9005663
TI  - [The interaction of pyruvate decarboxylase with the quinone-ferricyanide
      oxidative system].
AB  - Inactivation of yeast pyruvate decarboxylase in the presence of substrate and
      oxidative system containing substituted quinone and ferricyanide has been
      investigated. It was established that ferricyanide at pH 5.2-6.4 can prevent
      irreversible inactivation of the pyruvate decarboxylase caused by the concerted
      action of pyruvate and substituted quinone. The influence of ferricyanide which
      depends on the redox potential of the substituted quinone is decreasing in a
      series tetramethyl-p-benzoquinone, trimethyl-p-benzoquinone, 2-methyl-5-isopropyl
      p-benzoquinone. It is supposed that the effect of the oxidative system partially
      converting the nonoxidative to oxidative function of pyruvate decarboxylase is
      attributed to the oxidation of active acetaldehyde by substituted quinone and
      reaction of resultant semiquinone radical with ferricyanide.

PMID- 9005664
TI  - [Solubilization of the AMP deaminase in the muscles of the teleost fish
      Scorpaena].
AB  - A considerable amount of AMP deaminase (AMPDA) in animal muscles is linked with
      myofibrils. This link is disturbed with growth of the ionic strength. A smooth
      increase of AMPDA solubilization has been showed in experiments with rabbit
      muscles when KCl concentration grew from 0 to 500 mM. Earlier we showed at trout
      muscles that an increase in KCl concentration from 0 to 200 mM in the
      homogenization medium induced growth of the bound enzyme portion followed by its
      decrease at the range of KCl concentrations 300-500 mM. Similar results were
      obtained in experiments with the sea scorpion muscles, which shows specific
      character of AMPDA interaction with myofibrils in teleost fish muscles.
      Comparison of the pH influence on AMPDA extraction from Scorpaena and rabbit
      muscles supported the idea on the specific character of this enzyme binding in
      the teleost muscles.

PMID- 9005665
TI  - [The kinetic and catalytic properties of Penicillium vitale catalase].
AB  - The steady-state kinetics of catalytic action of Penicillium vitale catalase has
      been studied. The enzyme reaction conforms to the Michaelis-Menten equation,
      which is shown by considering the initial velocity of the enzyme-catalytic
      reaction with increased concentrations of hydrogen-peroxide and sodium perborate.
      The parameter Km value is rather large (231-259) mM. On the other hand the Pen,
      vitale catalase is one of the more active enzymes and shows kcat values equal to
      0.8-3.0 x 10(-6) s-1 and kcat/Km ratio of the order of 0.4-1.2 x 10(7) M-1 s-1.
      The enzyme reaction conforms to the Arrhenius equation when the temperature
      varied from 0 to 60 degrees C. It shows a slight temperature dependence and
      extremely low Ea value: 1.48 kcal/mol.

PMID- 9005667
TI  - [The normal tear fluid and decreased tearing in patients with Sjogren's disease
      and Sjogren's syndrome. I. The protein and glucose content].
AB  - Studies of total proteins, lysozyme and glucose in 25 patients (50 eyes) with
      Sjogren's disease and 26 patients (52 eyes) with Sjogren's syndrome have revealed
      a statistically significant reduction of tear production in patients vs. the
      normal subjects. The results obtained can be used both for diagnostic and
      therapeutic, purposes, in particular for dry-eye patients.

PMID- 9005666
TI  - [The effect of the implantation of the human apo A-I gene on the function of the
      hepatocyte plasma membrane in rats].
AB  - Evidences are given that implantation of human apo A-I gene to experimental
      animals induces essential changes in the functional state of hepatocyte plasmatic
      phospholipid composition, hyperpolarization development, as well as changes in
      the Na, K-ATPase and adenylate cyclase activities. The presence of generalized
      cell reaction is evidenced from the fact than biosynthesis of summary proteins
      gets enhanced during the above changes.

PMID- 9005668
TI  - [The normal tear fluid and decreased tearing in patients with Sjogren's disease
      and Sjogren's syndrome. II. The lipid content].
AB  - Studies of total lipids--squalene, cholesterol and sterol ethers, fatty acids and
      their ethers, lanosterol, oxysterols and phospholipids in 25 patients (50 eyes)
      with Sjogren's disease and 26 patients (52 eyes) with Sjogren's syndrome have
      revealed a statistically significant reduction of phospholipid quantities and an
      increase in fatty acids, and cholesterol in patients vs. the normal subjects.
      Possible influence of lipid components on the structure and function of the tear
      pellicle is discussed.

PMID- 9005669
TI  - [Biochemical changes in the brain of the root vole (Microtus oeconomus) from a 30
      kilometer zone around the Chernobyl Atomic Electric Power Station].
AB  - Deviations in lipid peroxidation parameters and in activity of dehydration
      enzymes in the brain of the tundra voles inhabiting areas with higher level of
      technogenic contamination (the 30-km zone of the Chernobyl NPP and the Republic
      of Komi) have been analyzed. During the first years after the disaster a decrease
      in the lipid antioxidative status of the brain and dehydrogenase activity,
      changes in the lipid composition of voles trapped in the disaster zone in
      comparison with control ones were more significant. Relative stabilization of the
      phospholipid composition with low antioxidizing activity of lipids and slight
      activity of succinate and piruvate dehydrogenases has been observed in a distant
      period of analysis.

PMID- 9005670
TI  - [The action of low doses of gamma irradiation on the function of the glutathione
      system in corn (Zea mays L.)].
AB  - The glutathione system is the protecting system of all alive organisms. The paper
      is devoted to the study of the state of some components of the glutathione system
      in plant objects taking into account that forms differing in genome complexity
      vary in their reaction on the effect of the environmental factors. A series of
      experiments was fulfilled to study the influences of gamma radiation (the dose of
      2.58 x 10(-3) C/kg) on growing corn seeds, differing in genome complexity.
      Biochemical indices were taken every 12 hours from the moment of seeding, which
      made it possible to watch the functioning of the glutathione protecting system in
      embryos, roots and shoots during the first seventy-two hours of growing. All the
      forms investigated responded to gamma radiation increasing the level of the
      glutathione peroxidase activity and showing no dependence on the genome
      complexity. Embryos of lines 102 and 502 did not respond to radiation, whereas in
      hybrids the level of restored glutathione fell, that confirmed more sensitive
      protecting system of hybrids.

PMID- 9005671
TI  - [The phospholipid composition of the heart in rats with acute vasopressin
      modelled myocardial ischemia].
AB  - The phospholipid composition of the heart of intact and experimental animals has
      been studied under conditions of simulated acute myocardium ischemia. It is shown
      that already at the 10th min the phospholipid composition of the heart ventricles
      changes expressively. The absolute amount of phosphatidylcholine,
      phosphatidylserine, diphosphatidylglycerol and phosphatidylglycerol decreases
      reliably. In this case lysophosphatidylethanolamine which is absent in control
      rats is identified. The amount of other phospholipids does not vary.
      Simultaneously the percentage of individual phospholipids varies: the
      phosphatidylethanolamine level significantly increases against the decrease of
      phosphatidylcholine and phosphatidylserine. As a result of the study of the
      amount of acylic and plasmalogenic forms of phospholipids it has been found that
      the level of the diacylic form of phosphatidylcholine in experimental animals
      falls. The data obtained testify to a definite participation of phospholipids in
      the pathogenesis of the acute myocardium ischemia.

PMID- 9005672
TI  - [Projections and fiber characteristics of sensory afferents of the anterior
      cruciate ligament in an animal experiment].
AB  - The sensory innervation of the rabbit anterior cruciate ligament was studied by
      retrograde tracing technique using wheat-germ-agglutinin-horseradish-peroxidase
      (WGA-HRP) and Fast Blue as neuronal tracers. Injection of the tracer into the
      ligament was followed by histo- and immunohistochemical investigation of labelled
      nerve cell bodies located in the dorsal root ganglia. In 4 animals we injected
      the tracer into the joint cavity to label general joint afferents. The segmental
      distribution of retrogradely labelled neurons following injection into the
      anterior cruciate ligament (L6, L7, S1) is significantly different from the
      distribution pattern after injection into the knee joint (L4-S2). Retrogradely
      labelled nerve cells innervating the anterior cruciate ligament were further
      investigated using immunohistochemical and morphometric analysis. The sensory
      innervation of the anterior cruciate ligament is therefore comprised of at least
      2 different qualities of sensory afferent nerves: 1. Small neurones
      immunoreactive to the inflammatory peptide substance P most likely transmitting
      nociceptive information centrally (44%). 2. Large, presumably fast conducting A
      fibre-afferents characterized by neurofilament proteins transmitting
      proprioceptive information from corpuscular mechanoreceptors (43%). The results
      of this study put further weight to the importance of the sensory role of the
      anterior cruciate ligament using neuroanatomical and immunohistochemical
      techniques.

PMID- 9005674
TI  - [Functional fracture treatment of the upper arm].
AB  - Using a functional brace, we treated 67 patients who had a fracture of the
      humeral shaft over a 5-year period from 1987 to 1992. We analysed several
      parameters of the fractures to discover those which influence healing. Desault,
      plaster cast or traction were used before applying a brace in an average time of
      15 days. The osseous consolidation was 10 weeks in the average. The functional
      results were very good and good in 78.3%, acceptable in 18.3% and poor in 3.4% of
      the cases. Twelve humeral-shaft fractures were associated with a radial nerve
      palsy. Every patient recovered a full radial nerve function under the treatment
      with a functional brace. The retentive management of an operative treatment of
      humeral-shaft fractures associated with a nerve injury can be supported because
      of our experience.

PMID- 9005673
TI  - [Does the degree of dislocation correlate with therapy procedure in supracondylar
      humerus fractures in childhood?].
AB  - Hundred and twenty-eight supracondylar fractures of the humerus were studied
      retrospectively after an follow-up time of 4.3 years (1 to 17.8 years). In 87
      cases (68%) the operative procedure was the closed reduction and percutaneous
      crossed-pin fixation for 19 fractures type III (56%). 22 fractures type II (76%)
      and 46 fractures type I (85%), whereas 41 fractures were treated by open
      reduction and crossed-pin fixation. The findings were evaluated according to
      "Flynn's criteria" leading to the following results: "excellent" 77 times
      (60.2%), "good" 44 times (34.4%) "fair" 3 times (2.3%) and "poor" 4 times (3.1%).
      Our results show that with approximately 50% of all fractures type III the
      treatment by closed reduction and percutaneous crossed-pin fixation leads to a
      very good long-term result. On the other hand, rotated or interponated fractures
      type I and II require an open reduction and crossed-pin fixation. Independent of
      the type of fracture, the closed reduction and percutaneous crossed-pin fixation
      should always be taken into consideration. Exceptions are open fractures and
      those with multiple fragments.

PMID- 9005675
TI  - [Indications and use of "AO pinless fixateurs". A preliminary report].
AB  - Improvements in techniques for the management of open tibial fractures with the
      external fixator have made a great impact on the final results in recent years.
      More recently this system has been discussed controversially. The longer
      treatment takes, the more likely it is that complications will occur when relying
      solely on the conventional external fixator. The new pinless fixator for the
      tibia was designed to overcome these problems. Early conversion to a more stable
      implant is one of the primary goals of this system. In this article the pros and
      cons are presented in detail and the limitation of this device explained.
      Moreover first clinical experiences are summarized and possible additional
      indications highlighted.

PMID- 9005677
TI  - [Socioeconomic principles of medical care].

PMID- 9005676
TI  - [Slit drainage in hip endoprosthesis--also an alternative in trauma surgery? A
      prospective follow-up study].
AB  - Forty-four patients undergoing elective hip joint operation were analyzed to
      assess whether a new slit-suction drainage is less painful than the regular Redon
      suction drainage. Main endpoint of the study was the effectiveness to draw off
      secretion and the pain at the time of removal of the drainage. Other endpoint was
      the rate of postoperative complications. At the time of removal patients with
      slit drain rarely complained about pain (p < 0.01). On contrary, patients with
      Redon drain always complained about pain. Clotting were seldom shown in slit
      drains and were frequently shown in Redon drains. Both slit drains and Redon
      drains were effective to drain secretion. As the new slit drain was more
      comfortable for patients following hip joint repair slit drain should always be
      used as suction drainage.

PMID- 9005678
TI  - [Clinical use of polymerase chain reaction in diagnosis and monitoring of
      malignant diseases].
AB  - The polymerase chain reaction (PCR) has revolutionized the diagnosis of
      leukemias, lymphomas and solid tumors over the past 10 years. This molecular
      method can amplify tumorspecific DNA or RNA markers by a factor of up to 1 x
      10(6). Clinical applications include: (1) improvement of histologic diagnosis
      through the detection of clonality and definition of molecular markers
      specifically associated with certain disease; (2) prognostic assessment at
      diagnosis, with impact on initial therapeutic decisions; (3) monitoring of
      minimal residual disease and early detection of impending relapse after
      chemotherapy or bone marrow transplantation; (4) detection of residual tumor
      cells in bone marrow and peripheral blood stem cell harvests; (5) diagnosis of
      hereditary tumor syndromes. A number of these PCR assays is already incorporated
      in routine laboratory diagnostic procedures, especially in acute and chronic
      leukemias. The final goal of the clinical application of PCR is the development
      of risk adapted therapeutic concepts for neoplastic disease.

PMID- 9005679
TI  - [Immunoglobulin A in saliva of children: age dependence and effect of respiratory
      tract diseases].
AB  - Immunoglobulin A (IgA) plays an essential role in the local defence mechanism and
      is part of the immunologic system. It is transported to the endothelial surface
      either as a monomer or as a dimer of two molecules of IgA connected by a j-chain
      and attached to a secretory component. The aim of the present study was to assess
      the relation of salivary IgA to the age of children and to assess a possible
      influence by acute and chronic respiratory diseases. IgA was measured in the
      saliva of altogether 230 children by means of radial immunodiffusion (LC-IgA
      Partigen, Behring) following a standardised protocol. Relation to age was
      measured in 159 healthy children aged one month to 15 years. The median of IgA
      was 36 mg/l with a range of 3.5-291 mg/l. There was no statistically significant
      relationship between salivary IgA and the age of the children. Median IgA in the
      saliva of children without any respiratory disorders (n = 169) was 36 mg/l (3.5
      291 mg/l), of children with acute respiratory diseases (n = 33) 51 mg/l (3.5-257
      mg/l) and of children with chronic respiratory diseases (n = 28) 47 mg/l (3.5-165
      mg/l). There was no statistically significant difference between these three
      groups. In conclusion, the results of this study show that IgA in the saliva of
      children may not be related to age or influenced by acute or chronic respiratory
      diseases.

PMID- 9005680
TI  - [Cryptosporidia associated gastroenteritis: epidemiologic study of children in
      Tyrol and Vorarlberg].
AB  - Stool samples from 523 children aged between 3 months and 6 years were examined
      for Cryptosporidium parvum by means of the direct immunofluorescence technique in
      March 1996. The specimens were sent to the Federal Public Health Laboratory in
      Innsbruck from general practitioners and pediatricians and from hospitals in
      Tyrol and Vorarlberg. The study was performed during the cold season in an area
      that does not employ surface water for the production of drinking water. Oocysts
      of cryptosporidia were detected as the sole agent in 4 out of 294 samples (1.4%)
      taken from children suffering from diarrheal disease, as well as in 1 out of 229
      samples (0.4%) of children in the control group. Duration of diarrheal disease
      varied from 2 days to 4 weeks. In addition, a 75 stool samples from Tyrolean
      calves were examined for cryptosporidia. Oocysts were detected in 3 out of 75
      stool samples (4.0%). Routine examinations for Cryptosporidium parvum in stool
      specimens of immunocompetent children with diarrhea do not seem to be necessary
      in Western Austria during the cold season due to the self-limiting course of the
      infection.

PMID- 9005681
TI  - [Homeopathy: principles, status of research, research design; comment].
AB  - This paper gives an overview of homoeopathy: 1. scientific foundations-2.
      problems and importance of research in homoeopathy-3. of research findings in
      basic and clinical research-4. future strategies of evaluation. Homeopathy is a
      medical discipline in its own right which is quite different from orthodox
      medicine in its basic tenets, its research paradigms and its practical approach
      to therapy, even though both methods are empirically founded and share the aim of
      healing the sick. When homoeopathy is pressed into a framework of research
      paradigms alien to its own approach, this is bound to engender difficulties
      because of the partial incompatibility. In spite of that, some studies with
      rigorous design have shown that homoeopathic remedies are effective. The
      important research findings are discussed and future strategies for evaluation
      are proposed.

PMID- 9005682
TI  - [The metabolism of foreign substances in the horse with reference to other animal
      species].
AB  - In this paper, the metabolism of xenobiotics in the horse, including differences
      to other species, is discussed. The most important metabolic reactions of phase I
      (oxidation, reduction and hydrolysis of substrates), as well as of phase II
      (conjugation of substrates with glucuronic acid, sulphuric acid, acetic acid,
      alkyl groups, amino acids, amino acid derivatives, glutathione etc.), are
      discussed and enzymes involved in the metabolic reactions are considered.

PMID- 9005683
TI  - [The effect of combolen on the erythrocyte distribution in the dog].
AB  - The effect of Combolen (3.9 mg/kg bw s.c.) on the distribution of erythrocytes in
      dogs was investigated. After application of Combolen, the hematocrit of the
      animals decreased exponentially within 1 h by 21%. The reversal of the reduction
      began from 2 h after the time of application, amounting to 4% within the first
      day and finishing by the fourth day. After injection of 51Cr-labelled
      erythrocytes, radioactivity in the circulation of Combolen-treated dogs decreased
      exponentially within 2 h by at least 30%. It was concluded that the dog's spleen,
      under physiological conditions, contains about 10% of the animal's blood. The
      time-courses of the decrease of hematocrit and radioactivity in the circulation
      were found to be very similar. In accordance with this observation, a high
      correlation (r = 0.97) between the level of radioactivity after injection of
      radio-labelled erythrocytes and the corresponding hematocrit values after
      application of Combolen was found. After application of erythrocytes, labelled
      with 99mTc, an extensive distribution from the circulation into the spleen was
      observed by scintigraphy. This process can be understood by using a closed
      compartment model. An equation, based on this model, describes the observed time
      course of the hematocrit values, as well as the number of 51Cr-labelled
      erythrocytes, in Combolen-treated dog. Presumably, the observed effect of
      Combolen is the result of the relaxation of the smooth muscle cells in the
      trabeculae of the spleen, caused by central-nervous depression of sympathetic
      tone. Combolen seems to be a suitable tool in pre-clinical testing of a novel
      blood preserve with dog as a test animal. Its potent ability to eliminate
      erythrocytes from circulation is distinguishable from the sequestration of
      damaged red cells. Furthermore, its ability to prevent the spleen from
      uncontrolled hematocrit modulating actions in addition to its sedative effects is
      considered to be an invaluable advantage.

PMID- 9005684
TI  - [Changes of serum enzymes, lactate and hemoglobin concentrations in the blood of
      young trotting horses due to training exertion].
AB  - Until the age of about 2 years, trotters normally grow up on pasture without any
      kind of training. In the stud farm Lindenhof (Templin, Germany), however, these
      first 2 years are used for a special fitness training for the young animals: 2-3
      times a week, a group of the yearlings is forced to run a distance of about 1700
      m on a track at an average speed of up to 10 m/s. Until now, little was known
      about changes of blood parameters which may occur during such special exercise.
      This study therefore investigated the activity of selected serum enzymes
      (aspartate-amino-transferase (AST), alanine-amino-transferase (ALT), gamma
      glutamyl-transferase (gamma-GT), lactic dehydrogenase (LDH), alkaline phosphatase
      (AP), creatine kinase (CK)) and the variations of hematocrit, hemoglobin,
      lactate, protein, and urea concentration before and after exercise. Except for
      activity of AP and CK and concentration of urea, all parameters showed a distinct
      increase after exercise. In particular, the rise in lactic-acid concentration
      with values up to 23.08 mmol/l was remarkable, however, none of the parameters
      reached a pathological level. It is therefore concluded that exercise for young
      trotters over a medium distance-even at high speed-does not cause any injury of
      myocardium, skeletal muscles or liver cells.

PMID- 9005685
TI  - [Familial cancer of the breast].
AB  - Genetic, cultural and environmental factors are influences shared in familial
      breast cancer. The objective of this study was to evaluate the prevalence of
      familial breast cancer and its association with social and clinical
      characteristics of women. A hospital-based descriptive study was made, and 300
      patients with the diagnosis of breast cancer, made in 1992, were investigated.
      17,4% of the women had a history of familial breast cancer. The presence of a
      positive history for familial breast cancer was associated with high social level
      for post-menopausal women. Age at diagnosis was older for women whose affected
      relative was their sister, not their mother. The need for the continuing efforts
      of epidemiologists, pathologists and geneticists to recognize the explanatory
      model of the disease is emphasized.

PMID- 9005686
TI  - [Neonatal screening of hemoglobinopathies in a population residing in Portugal].
AB  - The primary objective of newborn screening of hemoglobinopathies is the early
      identification of infants with sickle cell disease, as they are at increased
      clinical risk. Other goals include the identification of other types of
      clinically significant hemoglobinopathies and the detection of heterozygous
      carriers followed by the screening and counselling of family members. We
      performed a pilot study for the neonatal screening of hemoglobinopathies in 400
      samples of cord blood taken from a maternity in Lisbon. We did not find any
      newborn with sickle cell disease. Six samples were from sickle cell
      heterozygotes, the respective families were studied and informed. We looked for
      the presence of alpha-thalassemia at birth in 100 consecutive samples of cord
      blood, by the presence of Hb Bart's, abnormal red blood cell indices and alpha
      globin genotype. The results show an incidence of 10% of alpha-thalassemia (
      alpha) carriers and 4% of triple alpha-globin gene carriers. The authors discuss
      the feasibility of neonatal screening of hemoglobinopathies in a Portuguese
      speaking population consisting of a low prevalence of Hb S trait autoclonous
      group and a high prevalence immigrant minority.

PMID- 9005687
TI  - [Multicenter study of isolated micro-organisms resistant to antimicrobials in 10
      Portuguese hospitals in 1994].
AB  - In 1994, Microbiology Laboratories of ten Portuguese hospitals analysed isolated
      microorganisms found in blood and urine samples and studied antimicrobial
      susceptibilities of the most frequent bacterial pathogens. From 63780 blood
      samples, the most frequent were Staphylococcus spp. and from 69189 urine samples
      significant numbers of Escherichia coli, Enterococcus spp., Pseudomonas
      aeruginosa and Candida spp. were isolated. Escherichia coli strains (c.7000)
      revealed a low percentage of resistance to antibiotics with the exceptions of
      ampicillin (48%) and co-trimoxazol (25%). Klebsiella pneumoniae isolates (c.2000)
      revealed important resistance to ampicillin (98%), cephalotin (31%), co
      trimoxazol (38%) and gentamicin (28%), while values for 3rd generation
      cephalosporins varied among hospitals, with several strains showing phenotype of
      extended-spectrum beta-lactamase. A great variation in resistance values of P.
      aeruginosa (c.4000) was found in relation to the antibiotics as well as to the
      hospitals. Resistance to methicillin in S. aureus (c.6000) was high, reaching an
      average of 47%, and it was even higher with S. epidermidis (c.3000) and S.
      haemolyticus (c.650). Only vancomycin was always active against these strains. In
      E. faecalis (c.2500) resistance was of 2% to ampicillin, 35% to gentamicin, 45%
      to streptomycin and 1% to vancomycin. E. faecium isolates (c.300) showed the most
      worrying results with 70% resistance to ampicillin, 42% to gentamicin, 59% to
      streptomycin and 9% (30 strains isolated in 5 hospitals) to vancomycin.
      Vancomycin resistant strains were also resistant to all other antibiotics.

PMID- 9005688
TI  - [Chlamydia trachomatis in family planning. Is screening necessary?].
AB  - The authors used cellular cultures obtained from endocervix samples in order to
      determine the predominant factors of infection caused by Chlamydia trachomatis in
      a population of 391 women who attended a family planning consultation. The
      authors studied the relation between the infection and the following variables:
      age, geographical origin, social class, marital status, history of sexually
      transmitted diseases (STD), risk behaviours, contraceptive methods and attitudes
      towards both the disease and therapy. Chlamydia trachomatis was isolated in 7
      women (1,8%). The highest infection rates were found in the following categories:
      women between the ages of 35-40 (4,9%), women who resort to hormonal
      contraception (3,4%), women between the ages of 20-25 (3,2%) and single women
      and/or women who do not have a regular partner (2,6%). No statistically relevant
      relation between the above variables and the infection was found, although a
      relatively high risk was revealed for women who resort to hormonal contraception
      (O.R = 7,4). The authors have concluded the following: 1. There is no need to
      proceed with the systematic universal screening of infection caused by Chlamydia
      trachomatis in the yearly family planning consultations for the low risk STD
      populations; 2. Hormonal contraception is a factor to be considered when
      selecting the women to be screened; 3. The yearly gynaecological supervision of
      women who attend family planning consultations is an important factor in checking
      the disease; 4. Information on the couple's attitude towards the disease and
      therapy is essential in the prevention of relapses.

PMID- 9005689
TI  - [Use of sulprostone in the medical evacuation of uterine contents].
AB  - The authors describe a one year experience in the Viseu District Hospital
      Maternity with the use of prostaglandin E2 analog Sulprostone to expel the
      conceptus. The drug was used in continuous intra-venous administration using a
      dilution of 1000 mcg of sulprostone in 1000 cc of saline solution. Initially the
      infusion rate was 0,90 mcg/min (XVIII drops/min) which, was altered to 1,50
      mcg/min (XXX drops/min) after a meeting in Espinho in the spring of 1994. The
      results are presented as success (complete expulsion of uterine contents),
      partial success and failure. Success (complete and partial) was obtained in 33
      cases (62%) and failure in 20 cases (38%). The longer the gestational age the
      more effective was the drug. Tolerance was very good. We concluded that
      Sulprostone is an excellent method for medical emptying of the uterus in second
      and third trimesters.

PMID- 9005690
TI  - [Inter-hospital transfer in pediatrics].
AB  - We present the results of a prospective study of the technical and human
      characteristics of the transport of children transferred from other Hospitals to
      our PICU. During eight months of 1994, 153 children were transferred and 138
      included in our study. Their ages varied between one month and fourteen years and
      the majority (60%) were males. 67% of the patients transferred required Pediatric
      specialties and 30% required surgical specialties. Accidents were the most common
      pathology (40%), followed by neurologic, respiratory and infectious situations
      (15% each) The most frequently used means of transport was an ambulance, in 88%
      of the cases. Only 12% of these were medically equipped and 10% had CPR material
      available. In 23% of the transports the patient was accompanied by both a nurse
      and a medical doctor. In 25% by a nurse only and in 14% by a medical doctor. None
      of them had training in transport medicine. The length of the transport varied
      between 30 min. and 14 h, with a mean of 2h. Ten patients had major complications
      during transfer. Their CCS on arrival at the PICU was > or = 3 in 55% of the
      cases. Based on these results we discuss the obvious need for a Pediatric
      Transport System in our country.

PMID- 9005691
TI  - [The Miller Fisher syndrome. Review of the cases of the Santa Maria Hospital].
AB  - A benign syndrome of acute ophthalmoplegia, ataxia, and areflexia is commonly
      known as the Miller Fisher syndrome. It is generally believed that Miller Fisher
      syndrome is a type of Guillain-Barre syndrome, but several authors believe it to
      be a separate clinical entity caused by a central nervous system lesion. Eight
      patients with Miller Fisher syndrome diagnosis, admitted to our department in the
      last 20 years, were reviewed. Neurophysiological studies were carefully reviewed.
      Our patients had a clinical presentation and evolution identical to that
      described previously. Neurophysiological abnormalities were found in all patients
      and were characteristic of a sensory axonal neuropathy, with damage of the facial
      nerves and occasional demyelination of peripheral nerves. The pattern of
      abnormalities is distinct from the usual features seen in Guillain-Barre
      syndrome. The CT scan, MRI, and Evoked Potentials investigations in our patients
      did not confirm central nervous system lesion. Nevertheless we did not exclude
      the possibility of coexisting damage to the central nervous system in some
      patients, as shown in Chronic Inflammatory Demyelinating Polyneuropathy.

PMID- 9005692
TI  - [Status epilepticus].
AB  - Status Epilepticus can assume as many forms as there are types of epileptic
      seizures, and its clinical outcome largely depends on the etiology. Convulsive
      Status Epilepticus is a common emergency associated with high morbidity and
      mortality, but prompt and appropriate pharmacological therapy can reduce both.
      The authors present a rational treatment protocol for this syndrome.

PMID- 9005693
TI  - [Color Doppler echography. Clinical applications].
AB  - The enormous success of Ultrasound is derived from its good spatial resolution
      and diagnostic accuracy. The most recent and most important application of
      Ultrasound is Color Doppler. Color Doppler has introduced the dynamic factor,
      allowing the superimposition, on the high-resolution image, of flow information.
      For the first time, detailed and non-invasive information is obtained that is not
      only morphological, but also functional, through the visualisation of organ flow
      and perfusion. The clinical applications of Color Doppler are briefly discussed,
      encompassing areas that have long been studied by Duplex Doppler, such as the
      carotid-vertebral and the peripheral vessels. The most recent applications are
      also reviewed, namely: Tissue characterisation; Hemodynamics of portal
      hypertension and arterial hypertension; The evaluation of renal and hepatic
      transplants; and erectile dysfunction studies.

PMID- 9005694
TI  - [Clinical pharmacokinetics. Present and future].

PMID- 9005695
TI  - [Individualized monitoring of the therapy with gentamycin using pharmacokinetic
      methods. Which method to choose?].
AB  - Gentamicin has an excellent cost/efficacy ratio for gram negative infections
      treatment. Its use is often limited in clinical practice by its narrow safety
      margins and a high incidence of toxicity. Gentamicin related nephrotoxicity is a
      major adverse effect, mostly in patients with other concomitant potential risk
      factors. As many other Authors we have found in our Internal Medicine Service
      during 1992 a gentamicin related nephrotoxicity incidence of 22.5%. Various
      empiric methods and nomograms have shown a significant incidence of error in
      predicting individualized gentamicin dosage regimens. Pharmacokinetics methods
      have demonstrated much better results regarding efficacy and toxicity. The aim of
      this prospective study carried out during 1993-1994 was to individualize by
      pharmacokinetics methods dosage regimens of gentamicin in patients with one or
      more concomitant risk factors of nephrotoxicity. The purpose of pharmacokinetics
      dosage regimens has been to achieve trough serum concentrations of gentamicin in
      therapeutics range-0.5 to 2 micrograms/ml-on the first 24 to 48 hours of
      treatment, and the maintenance in this range during all the treatment, avoiding
      both toxic and under therapeutic levels. The incidence of gentamicin related
      nephrotoxicity has been evaluated in this population. Twenty patients were
      studied: 18 males and 2 females aged 59.6 years (19 to 85). All had one or more
      potential risk factors for nephrotoxicity-65 years or more: 13, previous renal
      failure: 6, other nephrotoxic drugs: 10, diuretics: 4, dehydration: 5, congestive
      heart failure: 5, diabetes: 3, hypertension: 3. For the first 10 patients
      gentamicin dosage regimens have been determined by Sawchuk-Zaske pharmacokinetics
      method and for the subsequent 10 patients by Bayesian method. The two
      subpopulations had no significant differences regarding mean age, sex and
      potential risk factors for nephrotoxicity. Results of Sawchuk-Zaske method: 53
      trough gentamicin serum concentration were obtained; 86.8% were within the
      therapeutic range, 7.5% were toxic and 5.7% were under therapeutic. Results of
      Bayesian method: 44 determinations of gentamicin through concentrations were
      obtained; 86.3% within therapeutic range, 2.4% were toxic and 11.3% were under
      therapeutic. A great variability in pharmacokinetic patient's profile has been
      found and explains the great variability of individualized dosage regimens of
      gentamicin (30 to 320 mg/day). No patients had gentamicin related nephrotoxicity.
      Both pharmacokinetics methods lead to a efficient and save employment of
      gentamicin in patients with previous renal failure and other potential risk
      factors for nephrotoxicity.

PMID- 9005696
TI  - [Prevalence of chronic hepatic disease in Portugal. Apropos of a review carried
      out in a hepatology unit].
AB  - The chronic elevation of Aminotransferases is one of the most frequent
      indications for percutaneous Liver Biopsy (LB). From a retrospective study of LB
      performed in the Hepatology liver Unit of Santa Maria Hospital, between 1989 and
      1993, we correlated the histologic diagnosis with the etiology of liver disease,
      sex, age and the Aspartate aminotransferase/Alanine aminotransferase (AST/ALT)
      and Gama-Glutamyl transpeptidase (gamma GT) index in patients with chronic liver
      test abnormalities. 790 LB were reviewed retrospectively, of patients aged
      between 11 and 78 years, 68% males and 32% females. The most common etiology was
      Hepatitis C (34.6%), followed by Hepatitis B (20.1%) and alcohol (15.8%).
      Autoimmune diseases (Primary Biliary Cirrhosis and Autoimmune Hepatitis) were
      present in 3% of cases, and metabolic liver diseases in 1.4%. The distribution by
      sex revealed a predominance of Hepatitis C in both, alcoholic liver disease being
      more frequent in males (21.5% vs 3.9%). The main histological diagnoses were
      Chronic Active Hepatitis (27.2%), Liver Cirrhosis (19.5%), Steatohepatitis (9.5%)
      and minor lesions (24.6%). In alcoholic liver disease, 47.2% had Liver Cirrhosis
      and 16% Steatohepatitis; in Hepatitis B, Liver Cirrhosis was found in 12.6% and
      in Hepatitis C in 11.4%. Liver Cirrhosis had a prevalence between the 4th and 6th
      decade of life (82%) with a peak incidence in the 5th, and appeared earlier in
      Hepatitis B and later in Hepatitis C. The prevalence between sexes was similar.
      The main etiology of Liver Cirrhosis was alcohol (38.3%). The gamma GT index was
      greater in alcoholic liver disease (average 4.1) and was nearly twice in
      Hepatitis C than in Hepatitis B (1.7 vs 0.8). CONCLUSIONS: 1) Hepatitis C in our
      Hepatology Unit was the main indication for Liver biopsy. 2) The prevalence of
      alcoholic liver disease is greater in males, being the main etiology of Liver
      Cirrhosis. 3) The progression to Liver Cirrhosis seems to be similar in Hepatitis
      B and C. 4) The progression to Liver Cirrhosis is similar in both sexes, being
      dominant in the 5th decade of life. 5) The progression to Liver Cirrhosis is
      earlier in Hepatitis B than in Hepatitis C. 6) A gamma GT index elevation,
      without alcohol abuse, is suggestive of Hepatitis C. 7) Autoimmune and metabolic
      liver diseases seem to be rare in Portugal.

PMID- 9005697
TI  - [Apolipoprotein A1 and biliary lithiasis in hepatic cirrhosis].
AB  - A prospective study was performed in 67 male patients with cirrhosis, admitted in
      our Department during one year. Biliary lithiasis was found in 37% of patients.
      The occurrence of lithiasis was not related to age, weight or severity of liver
      disease. Seric total bilirubin was higher in lithiasic patients (p < 0.05).
      Apolipoprotein A1 levels were lower in those ones with lithiasis (p < 0.005).
      Apolipoprotein A1 was the only factor associated independently with the finding
      of lithiasis.

PMID- 9005698
TI  - [Limb amputations carried out in hospitals of the national health service in the
      years from 1990 to 1993].
AB  - This study was to assess the number of limbs amputations in Portugal State
      Hospitals over a four years period (1990 to 1993), analysing their incidence
      according to etiology, sex, average age, duration of hospitalization, level of
      amputation and mortality rate. The authors emphasise the levels of amputation
      which are mot favourable for an effective rehabilitation.

PMID- 9005699
TI  - [Utilization of forearm island flaps in reconstructive surgery of the hand. Which
      one is the best option?].
AB  - The authors report their clinical experience after seventy-six forearm island
      flaps, and analyse the different possible forearm flap options in hand
      reconstructions. The different flaps-based on the radial, ulnar, interosseous and
      septocutaneous ulnar vessels-are compared in what, concerns the importance of the
      sacrificed artery, adverse sequelae of the donor area and their versatility to
      close large skin defects as well as their capacity to reach distal areas of the
      hand. Their ability to provide sensate coverage and to replace bone and tendons
      is also compared.

PMID- 9005700
TI  - [Localization of brain electric sources in patients with focal epilepsy].
AB  - In this paper we discuss a non-invasive method to localize neural electrical
      sources using EEG data. In this method, the human head is modelled by a set of
      four concentric spheres with different conductivities which represent the scalp,
      the skull, the CSF and the brain or by three triangulated surfaces which
      approximate the exact head shape (in this model we do not consider the CSF layer)
      using NMR images. In this case the computer effort is very high, since the
      calculations imply thousands of equations. Therefore, the number of research
      groups working with this improved model, in the world, is very small. In both
      models, we assume that the neural source is a current dipole. This makes the
      model suitable for cases where the active brain areas are limited and localized.
      We discuss some error factors associated with the method, as the geometry of the
      head, the conductivity of the different layers and the number of electrodes used
      in the EEG measurements. Comparing the more realistic head model, with the
      spherical one we often have differences of 1-2 cm. However, we can reach even
      more pronounced differences in the frontal areas. Concerning the skull
      conductivity, we realized that it could introduce errors of 1-2 cm. We observed
      that at least 50 electrodes should be used only since 21 electrodes could imply
      errors of about 0.5 cm. The method was applied, both in the spherical version and
      the realistic one, to clinical cases of focal epileptic patients. The results are
      discussed in terms of the other clinical information available and they are
      coherent with the remaining clinical data.

PMID- 9005701
TI  - [TSH anti-receptor antibodies in Graves' disease].
AB  - The purpose of this study was to evaluate the sensitivity, specificity and
      predictive value of thyrotropin receptor antibody (TRAb) in the diagnosis of
      Graves disease. TRAb was tested by an isotopic receptor assay-TRAK Henning-in 80
      newly diagnosed, untreated Graves disease patients (group I), 63 with other
      thyroid diseases (group II) and 60 controls (group III). In group I, 11 patients
      were TRAb negative and 7 were considered in the gray area (TRAb between 9 and 14
      U/L). In group II, only 2 patients had TRAb 9 U/l and all controls were TRAb
      negative. For statistical analysis patients with TRAb in gray area were excluded.
      Sensitivity and specificity for this assay were 84.5 and 100% respectively.
      Predictive value of 100% affords certainty that a hyperthyroid patient with a
      positive TRAb has Graves disease, not sequining a scintigram.

PMID- 9005702
TI  - [Diabetes mellitus after renal transplant].
AB  - Posttransplant Diabetes Mellitus (PTDM) has traditionally been attributed to
      therapy with steroids, however with the introduction of Cyclosporine (cya) into
      clinical practice, an increase in the incidence of PTDM was noted. We studied the
      prevalence of PTDM in Renal transplant recipients and its clinical
      characteristics. MATERIALS AND METHODS: 355 patients were submitted to a renal
      transplant between 30/06/80 and 31/12/92. After stabilization of the doses of the
      immunosuppressive therapy we considered diabetic patients those with fasting
      glycemic values > or = 140 mg/dl and those with glycemic values between 100-140
      mg/dl were given to an oral glucose tolerance test (WHO criteria 1985). RESULTS:
      Posttransplant diabetes mellitus occurred in 28 patients (7.9%), 11 females with
      a mean age of 53.36 +/- 12.75 years and 17 males with a mean age of 51.05 +/-
      10.60 years. DISCUSSION: Due to the great prevalence of alterations in glucose
      tolerance and their adverse effects on the cardio-vascular system, we think that
      all renal transplant recipients should be screened.

PMID- 9005703
TI  - [Fluorescent products in the crystalline lens of type ii diabetic patients].
AB  - A body of evidence suggests that glycation of proteins and the resulting
      fluorescent products take part in the late complications of diabetes. The purpose
      of this study was to analyse the fluorescence of lens soluble proteins from
      diabetic patients. Soluble proteins were obtained from lens with cataract from 20
      type II diabetic patients and from 21 non diabetic controls with similar age. The
      fluorescence of the soluble fraction (EX-360 nm, EM -454 nm) was quantified as a
      parameter for glycation end products. The glycation of plasma proteins was
      quantified by fructosamine levels. The fluorescence mean in the group of
      diabetics was about twice the non diabetic value (p < 0.01). The fluorescence in
      the diabetics with retinopathy was higher than that of diabetic without
      retinopathy (p < 0.01). Fructosamine levels were: diabetics 3.1 +/- 1.1 mM, non
      diabetics 1.9 +/- 0.8 mM (p < 0.001). The results suggest the involvement of
      fluorescent products, resulting from glycation of proteins, in lens opacification
      in diabetic patients.

PMID- 9005704
TI  - [Profile of tropical diseases in Portugal].
AB  - The increased incidence of Imported Tropical Diseases in Portugal is correlated
      to a recent higher standard of living, influence of media and a consequent
      expansion of tourism, and above all to the close relationship existing between
      Portugal and Africa. The number and pathology (parasitic diarrhoeas, protozoal
      and helminthic infections) of in-patients with Tropical Diseases at the Unidade
      de Doencas Infecciosas, Parasitarias e de Medicina Tropical (UDIP-MT) were
      described, with special emphasis on Malaria (155 in-patients during the period
      from 1989 to 1993) and on Sleeping Sickness, where Eflornitin (DFMO) was for the
      first time used in Portugal. Finally, the impact of HIV epidemic on incidence and
      different clinical presentations of parasitic and other tropical pathology was
      also evaluated.

PMID- 9005705
TI  - [Atypical profile of markers of hepatitis B and vaccination].
AB  - We describe several atypical serological profiles of hepatitis B virus infection
      (HBV), which can arise difficulties in diagnostic and classification of the
      infection stage. Its knowledge is important in establishing a more accurate
      strategy of the screening of blood donors and candidates for vaccination. On the
      other hand, vaccination may be useful in interpretation of the serological
      profile. We also discuss the role of HBV mutants in this context.

PMID- 9005706
TI  - [Postgraduate training in gynecology and obstetrics. Results of an individual
      national survey of interns].
AB  - The national survey on the trainees in this specialty was conducted to find out
      the trainees' opinions and expectations regarding postgraduated in Gynecology and
      Obstetrics and professional opportunities. A total of 320 questionnaires were
      send to all the trainees registered with the Portuguese Medical Association. Some
      of the topics of this survey were: structure and quality; curriculum
      requirements; assessment and professional opportunities. We received a total of
      109 replies, which are presented in this article.

PMID- 9005707
TI  - [The history of malaria in Sa Tome. Considerations on an epidemic].
AB  - Using a historical approach of malaria control in the island of Sao Tome, the
      author describes the evolution of strategies used with special reference to the
      last 25 years. From a zero mortality rate in children under 4 years in 1981/83,
      malaria became the first cause of morbidity and mortality after the epidemic of
      1985/86. Malaria was introduced in 1493, when the virgin island was populated
      with individuals of various origins (Europe, Africa). The problem became more
      important as the population of Sao Tome increased in the XIXth century, with
      immigration of workers for cultivation of coffee and cocoa. At that time, methods
      of control of "fevers" were already defined including drainage of swamps,
      cleansing of the environment and use of quinine for prophylaxis and treatment. At
      the beginning of the XXth century, with the first epidemiological investigations,
      global plans of medical assistance and free delivery of chloroquine were
      elaborated. Between 1946 and 1967, localities were stratified according to their
      endemicity, the major vectorial species (Anopheles gambiae sp.) were identified
      and the parasitological indices were calculated. All species of the malarial
      parasites coexisted, Plasmodium falciparum being the most prominent. In 1968, the
      Mission of Eradication of Malaria was created. Between 1977 and 1983, anti
      vectorial control (indoor spraying, larvicides) resulted in a decrease of
      mortality rate. The interruption of the antivectorial control activities was
      responsible for the 1985/86 epidemic and the restoration of the levels of
      endemicity.

PMID- 9005708
TI  - [Aspiration cytology of the thyroid using a fine needle. Technical aspects].
AB  - Fine needle aspiration cytology is the diagnostic test of choice for evaluating
      thyroid nodules. It's an easy and inexpensive method with low mobility which
      allows a safe diagnosis in patients with goiter, a therapeutic approach in benign
      cystic lesions as well as an early diagnosis and therapeutic guidance in thyroid
      cancer. The authors report fine needle aspiration cytology technical aspects as
      well as its possible complications. The authors also report briefly the cytologic
      patterns and its differential diagnosis.

PMID- 9005709
TI  - [Imaging findings in hypertensive encephalopathy].
AB  - Hypertensive encephalopathy is a neurologic syndrome caused by a marked and rapid
      rise of blood pressure above baseline levels. Efficacy of current anti
      hypertensive drugs greatly diminished the frequency of this situation in which
      diagnosis is essentially based on clinical parameters. This can justify the few
      papers found in radiologic literature. Nevertheless it is sometimes important to
      exclude ischemic or hemorrhagic complications or establish a differential
      diagnosis with other neuropathologic conditions. Then a striking imagiologic
      picture of focal or diffuse reversible edema of cerebral white matter can be
      found. We present three clinical cases of hypertensive encephalopathy.
      Imagiologic findings are reviewed and correlated with the pathophysiologic basis
      of the disease.

PMID- 9005710
TI  - [Tuberculosis and hypercalcemia].
AB  - The authors present a case of disseminated tuberculosis in a patient under
      dialysis with endstage renal disease. Fever, nocturnal sweating, anorexia,
      asthenia, ascites, lymph node involvement and granulomatous involvement of the
      bone marrow were observed. In the twenty nine months of renal failure which
      preceded the beginning of the tuberculosis, serum calcium levels were normal or
      low-normal and there was a secondary hyperparathyroidism. During that period the
      patient was treated with calcium carbonate and calcitriol. At the onset of
      tuberculosis, serum calcium levels rose above normal. Treatment with calcium and
      calcitriol was withdrawn but hypercalcemia remained unchanged. Serum
      concentration of parathormone fell significantly. Antituberculosis drugs were
      started. The resolution of active tuberculosis was accompanied by normalization
      of serum calcium levels and by elevation above normal of serum concentration of
      parathormone.

PMID- 9005711
TI  - [Gastroduodenal, ileocolic and perianal Crohn's disease].
AB  - The authors present a case of Crohn's disease that initially showed common
      localisations, and later a rare gastro-duodenal involvement. When the definitive
      diagnosis of the latter was reached there were already signs of obstruction at
      the exit of the stomach. Treatment with Prednisolone I.M. and Omeprazole was not
      successful, and surgery was necessary as a last recourse to resolve the
      obstruction. A theoretic revision of the main clinical, diagnostic, and
      therapeutic aspects of this rare from of involvement of Crohn's disease is also
      presented.

PMID- 9005712
TI  - [Infection with hepatitis C virus in porphyria cutanea tarda].
AB  - The authors make a literature review on hepatitis C virus infection in porphyria
      cutanea tarda, illustrated by one clinical case. They also present some
      considerations about pathophysiologic mechanisms involved in this association.

PMID- 9005714
TI  - [Common alveolo-dental symptomatology and tumor pathology].

PMID- 9005713
TI  - [Hodgkin's disease in a patient with sarcoidosis].
AB  - We present the case of a 37 years old woman with mediastinal lymphadenopathy
      since the age of 13. At de age of 14, the patient presented a left cervical
      lymphadenopathy and the onset of episodic nodose erythema. One year later,
      histological examinations of an enlarged lymph node revealed sarcoidal
      granulomata. Corticotherapy was prescribed and the patient became asymptomatic.
      At the age of 31, the patient complained of asthenia and fever with left parotid
      tumefaction. Corticotherapy was therefore resumed with good response. Three years
      later, the patient presented left parotid tumefaction, left cervical
      lymphadenopathy and painful eye congestion. The patient was submitted to
      parotidectomy and lymphadenectomy. One month later, an ulceration with
      progressive enlargement developed in the surgical scar, and the patient suffered
      from asthenia, anorexia, weight loss, fever, nocturnal sweating and cervical and
      axillary lymphadenopathy. At Santa Maria Hospital, the patient's condition was
      diagnosed as Hodgkin's disease, mixed cellularity subtype, stage II Bb with local
      cutaneous involvement. The prescribed treatment was MOPP/ABV-8 cycles- and
      complete remission was achieved. The patient is still asymptomatic after a follow
      up of 6 years. Cutaneous involvement in Hodgkin's disease is rare and generally
      associated with advanced disease and poor prognosis, facts that did not occur in
      this case. The differential diagnosis between sarcoidosis and sarcoid reaction in
      Hodgkin's disease, the accidental coexistence of both entities and the evolution
      of sarcoidosis into lymphoma are also discussed. The sarcoidosis immune defect
      may be the result of the same immune disorder. No relationships between
      sarcoidosis and cutaneous involvement in Hodgkin's disease were found in the
      literature.

PMID- 9005715
TI  - [Oral tuberculosis: apropos of a case].

PMID- 9005716
TI  - [Oromandibular dystonia and botulinum toxins].
AB  - The authors describe the Meige's Syndrome also known as blepharospasm or
      mandibulo-oral dystonia. This Syndrome rather known by Neurologists and
      Ophthalmologists than by Stomatologists actually benefits by a specific treatment
      based on botulin toxins.

PMID- 9005717
TI  - [Mandibular fractures. An epidemiological study of a 10-year cohort].
AB  - From 01-01-1981 to 12-31-1990 512 patients with isolated mandibular fractures,
      161 patients with combined midfacial-/mandibular fractures and 15 patients with
      combined frontobasal-/midfacial-/mandibular fractures were treated. During that
      period the number of isolated mandibular fractures doubled, whereas the frequency
      of combined mandibular fractures was nearly constant. The male/female ratio was
      3.1 to 1. The more severe the combined mandibular fractures had been, the less
      female patients were concerned. Most of the patients were between 16 and 30 years
      old followed by 31 to 45 year old patients. The main reason for isolated
      mandibular fractures had been assaults, followed by falls and road traffic
      accidents, whereas most of the combined mandibular fractures were caused by road
      traffic accidents. The numbers of single and double fractures of the mandible
      were nearly equal. Certain and uncertain signs of fractures are mostly
      unreliable, so that an X-ray is needed. A combined conservative and surgical
      treatment shows the best results and guarantees the reintegration of the patient
      in the every-day life as early as possible.

PMID- 9005719
TI  - [National Register of Rheumatic Diseases in Children. The Spanish group of
      pediatric rheumatology].

PMID- 9005718
TI  - [Catch-22: current implication of the microdeletion in 22q11].

PMID- 9005720
TI  - [Evaluation of statistical procedures in the original articles of "Anales
      Espanoles de Pediatria": comparison of two different periods (1989-90 and 1994
      95)].

PMID- 9005722
TI  - [Tracheobronchial aspiration of foreign bodies in children].
AB  - OBJECTIVE: Our objective was to study the characteristics and follow-up of
      children admitted to our Pediatric Emergency Room (PER) due to tracheobronchial
      inhalation of foreign bodies (FB). PATIENTS AND METHODS: We have reviewed
      retrospectively the 55 cases admitted over the last five years to our PER in whom
      the diagnosis of FB inhalation was confirmed. RESULTS: Mean age was 4 years with
      the peak incidence (25) occurring between 1 and 2 years of age. The second risk
      group was 11 years (8). In 84% of the patients (46), there was a history of FB
      aspiration. Twenty-five percent of the children (14) presented at the hospital
      within 24 hours, and 18% (10) more than 1 week after inhaling the FB. Physical
      examination was normal in 5%. The X-ray findings were: air trapping (74%),
      atelectasis (13%), in cases admitted more than 1 week after aspiration, and were
      normal in 13%. Rigid bronchoscopy and subsequent removal of the FB was the
      treatment instituted in 53 cases. There were no deaths. The FB was located at the
      right bronchus in 67%. The ingestion of nuts accounted for the highest incidence
      (72%), occurring mainly in younger children. Inorganic bodies constituted the
      majority of the cases in children older than 9 years (p = 0.0000). CONCLUSIONS:
      1. Tracheobronquial inhalation of FB continues to not alarm the general
      population since only 25% presented at the hospital within 24 hours. 2. There are
      two risk groups, the second year of life (the largest) and the eleventh year, and
      they are different in the type of FB inhaled. 3. It is necessary to keep
      insisting on the methods of prevention.

PMID- 9005721
TI  - [Usefulness of oxygen saturation and peak expiratory flow in the management of
      acute asthma].
AB  - OBJECTIVE: The aim of the present study was to determine the usefulness of oxygen
      saturation (SaO2) and peak expiratory flow (PEF) in the assessment of severity of
      acute asthma and the discriminatory quality of their initial values in predicting
      the patient's hospitalization. PATIENTS AND METHODS: A prospective observational
      design was used. The study was carried out in the Emergency Department (ED) of an
      urban pediatric hospital with a 1993 census of 170,000 children. One hundred
      twenty-three children with previously diagnosed asthma, who presented to the ED
      with wheezing were included in the study. SaO2 and PEF levels were recorded upon
      arrival at the ED and after receiving initial treatment, prior to deciding the
      child's discharge or hospitalization. Children were treated according to the
      current practice guidelines. RESULTS: The mean SaO2 before and after the
      treatment was lower for the children who required admission to the hospital, 91.8
      +/- 2% and 92.9 +/- 2%, respectively, than for those who were sent home, 96.1 +/-
      3.2% and 96.5 +/- 1.8%, respectively (p < 0.01). The same happened with the PEF
      values, 41.3 +/- 17.8% and 54.8 +/- 17.9% for the admitted patients versus 68.3
      +/- 17.9% and 90.1 +/- 10.6% for those sent home. An initial SaO2 of 95% had a
      sensitivity of 83% and a specificity of 79%. The optimal cut-off point for the
      PEF was 50%, with a sensitivity and a specificity of 81%. CONCLUSIONS: Our study
      shows that SaO2 and PEF can satisfactorily assess the seventy of acute asthma in
      children and that their initial values can predict the patient's outcome.

PMID- 9005723
TI  - [Anthropometric assessment of the nutritional status of the adolescent population
      of Cadiz (Spain)].
AB  - OBJECTIVE: The results of a series of anthropometrical values of nutritional
      nature, which were used to determine corporal composition, are presented.
      PATIENTS AND METHODS: The samples were taken from schools in the city of Cadiz. A
      total of 945 young people between the ages of 10 and 17 years were used. In each
      case, tricipital skinfold thickness, Quetelet's index, brachial fat area and
      brachial adipose muscular quotient were determined. RESULTS: A comparison of the
      values we obtain with those of national studies showed our figures to be higher.
      CONCLUSIONS: The figures given for our adolescent population are intended to
      serve as a reference point for use in nutritional studies in this geographical
      area.

PMID- 9005724
TI  - [Suprapubic bladder aspiration. Utility and complication].
AB  - OBJECTIVE: This study aims at evaluating the usefulness of suprapubic bladder
      aspiration (SBA) in order to diagnose urinary tract infection (UTI), enumerating
      the complications and describes those found in the existing literature. PATIENTS
      AND METHODS: We have reviewed the 668 SBAs carried out on 642 children over a
      period of 3 years. The ages of the children varied from neonate to 5 years. Urine
      cultures were regarded as positive when any one single germ showed bacterial
      growth signs. RESULTS: Ninety-four UTIs, 14.6% of the total samples studied, were
      detected, five of which were in newborns. Infection by Escherichia coli comprised
      87.2% of the total. Two complications were observed: needle breakage and vaginal
      bleeding. CONCLUSIONS: SBA is a reliable method, with hardly any complications,
      and is essential for the accurate diagnosis of UTI. However, it must be used with
      a more restrictive criterion in the neonatal period.

PMID- 9005725
TI  - [Pneumonia due to Haemophilus influenzae type b in children: presentation of 24
      cases].
AB  - OBJECTIVE: Due to the higher incidence in invasive infections, the changes
      observed in the sensitivity of this microorganism during the last decade and the
      seriousness of pulmonary infections in children, the objective of this paper is
      to review the clinical and epidemiological characteristics of Haemophilus
      influenzae type b (Hib) pneumonia, as well as to give an update of treatment.
      PATIENTS AND METHODS: Twenty-four children diagnosed between 1973 and 1992 are
      reviewed using the following criteria: clinical manifestations of pneumonia,
      radiology and isolation of the microorganism. RESULTS: The annual average was 7.8
      cases/100,000 children under 5 years of age. More females were affected (58.3% vs
      41.6%). Of the cases studied, 58.3% of the children were under one year and 83.3%
      under 2 years of age. Fever was the most common clinical manifestation (95.8%).
      Blood cultures were positive in 21 cases (87.5%); pleural effusion culture
      contributed to the diagnosis in two other cases (8.3%) and deep bronchial
      aspirate in one other case. Of the Haemophilus influenzae type b strains 62.5%
      were resistant to ampicillin and 100% were sensitive to second and third
      generation cephalosporins. Three infants with chronic illness died (12.5%).
      CONCLUSIONS: Hib pneumonia is an infection usually affecting children younger
      than 2 years of age. Its clinical manifestations are indistinguishable from those
      of other microorganisms. Blood culture is the most useful technique to confirm
      the diagnosis. The increase in resistance to classical treatment (ampicillin)
      obliges us to consider amoxicillin-clavulanic as the selected empirical
      treatment. Second and third generation cephalosporins may be considered a good
      alternative. There is a high mortality in children with chronic illness.

PMID- 9005726
TI  - [Primary hyperlipidemia in children and adolescents: effects of dietary and
      pharmacological intervention].
AB  - A retrospective study was performed on children with hypercholesterolemia or
      hypertriglyceridemia referred to the Endocrine Clinic of the Nino Jesus
      University Hospital over a period of 5 years. One hundred twenty-seven children,
      from 2 to 16 years of age, were followed. The subjects were classified into the
      following groups: 90 with primary hyperlipidemia [55 polygenic
      hypercholesterolemia (PH), 23 familial hypercholesterolemia (FH) and 12 with
      familial combined hyperlipidemia (FCH)]; 2 with secondary hypercholesterolemia
      and 35 were found to have normal cholesterol and triglyceride values. All
      patients with primary hyperlipoproteinemia were instructed to carry out dietary
      intervention during a 6 month period, following the step I recommendations of the
      National Cholesterol Education Program (NCEP). The following results were
      obtained: In the group of children with PH and FH a decrease in total and LDL
      cholesterol was observed (p < 0.0001 for both groups). In the group of FH, a
      decrease in the LDL/HDL ratio was also observed (p < 0.01). In contrast, the
      group of children with FCH did not show any changes in the lipoprotein pattern
      after dietary intervention. In the three groups studied, no statistically
      significant differences were observed in the remaining parameters (HDL-C, VLDL,
      and apo A1) after dietary intervention. Lp(a) levels above 30 mg/dl were observed
      in 25%, 37% and 46% of the children with PH, FH and FCH, respectively. Nine
      patients with FH were treated with resins for 3 months. In these children a
      decrease in total and LDL cholesterol, apo B and in the LDL/HDL ratio was
      observed (p < 0.05). No changes in Lp(a) and HDL-C were observed in this group of
      children. In our experience, dietary intervention to reduce fat and cholesterol
      intake in children with primary hyperlipoproteinemia, a population at high risk
      of developing atherosclerosis, is safe and useful. The treatment with resins in
      children with FH improves their lipoprotein profile.

PMID- 9005727
TI  - [New markers of atherogenic risk: hemorrheological profile in children and
      adolescents with familial hypercholesterolemia].
AB  - OBJECTIVE: Recent studies in adults have shown that hemorrheological alterations
      are predictive of early cardiovascular disease, but it is unknown if they are
      related to hyperlipemia or are secondary to an established atherosclerotic
      process and if they appear during childhood. PATIENTS AND METHODS: Several
      rheological parameters have been studied in 36 patients with familial
      hypercholesterolemia (FH). These patients were between 2 and 16 years of age and
      12 of them were being treated with cholestyramine. Thirty-five controls (CG) were
      individually matched for age and sex. RESULTS: The FH patients treated with
      cholestyramine did not show significant differences in any of the six rheological
      parameters that were studied when compared to the other patients. Therefore, the
      results of the FH group were analyzed as a whole when they were compared with the
      CG. The following significant differences were found: Index of erythrocyte
      aggregation at stasis 5.0 +/- 1.2 vs 3.6 +/- 1.0 (p < 0.001), index of
      erythrocyte aggregation at low rate of blood shears 8.1 +/- 1.7 vs 6.9 +/- 1.4 (p
      < 0.001) and plasma viscosity 1.19 +/- 0.11 vs 1.16 +/- 0.04 mPA/s (p < 0.01).
      There were no significant differences in the plasma fibrinogen nor in the blood
      viscosity at shear rats of 230/s and 23/s. Carotic echo-doppler was taken in the
      HF patients which was normal, indicative of the absence of atherosclerosis
      lesions in the fibrous plaque phase. CONCLUSIONS: These results indicate that
      there are hemorrheological alterations in absences of established atherosclerotic
      lesions, which are associated with hypercholesterolemia and that emerge in the
      pediatric population. Therefore, research in FH patients offers new data to
      evaluate the atherogenic risk and its complications.

PMID- 9005728
TI  - [Risk and outcome factors in necrotizing enterocolitis].
AB  - OBJECTIVE: The objective of this study was to identify risk and outcome factors
      in necrotizing enterocolitis (NEC). PATIENTS AND METHODS: We have studied 72
      cases of NEC collected from 1987 until 1994 in the three hospitals of the
      integrated Unit. A case-control study matched for gestational age and center was
      performed for 26 risk factors. Conditional logistic regression was used in
      significant bivariate variables. The 18 outcome factors had the same statical
      treatment, but without the paired design. RESULTS: Serous infections previous to
      NEC, apnea and feeding increments greater than 20 cc/kg/day have been identified
      as risk factors for preterm babies (p < 0.05). Severe acidosis and
      pneumoperitoneum have been found significant outcome variables, but with very low
      discriminatory capacity. CONCLUSIONS: It has been found difficult to identify
      risk factors for NEC besides the gestational age. Outcome factors have very low
      sensitivity. Preventive treatment should be directed to decrease the effect of
      the inflammatory mediators in the gastrointestinal tract.

PMID- 9005729
TI  - [Seasonal differences in neonatal jaundice].
AB  - OBJECTIVE: It is important to consider additional factors known to affect serum
      bilirubin levels in the newborn and that might yield new criteria for the
      diagnosis of physiological and non-physiological (or pathological) jaundice. The
      aim of this study was to analyze the seasonal differences of pathologic
      hyperbilirubinemia during the neonatal period. PATIENTS AND METHODS: One hundred
      and sixty-one consecutive newborn infants with pathologic hyperbilirubinemia who
      were admitted to our Neonatal Care Unit during three years were studied
      prospectively. Jaundice (and hyperbilirubinemia) was considered pathological if
      the time of appearance, duration or pattern of serially determined serum
      bilirubin concentrations varied significantly from that of physiological
      jaundice. Complete obstetric histories were obtained and examinations were
      performed at the time of admission. Seasonal differences in this population were
      studied. RESULTS: We found more pathologic hyperbilirubinemia during the fall and
      less in winter, but these differences between seasons were not statistically
      significant. The only statistically significant differences were found in summer:
      more breastmilk jaundice (p < 0.05), more infants with maximum serum bilirubin >
      20 mg/dl (p < 0.05) and more admissions from external delivery rooms (p < 0.05).
      We have not documented an association between weight loss of the newborn and the
      level of hyperbilirubinemia. CONCLUSIONS: The higher temperature during the
      summer could contribute to the qualitative and quantitative differences found in
      this season, with a greater influence of breastfeeding and more severe
      hyperbilirubinemia. In general investigation of the cause of hyperbilirubinemia
      in healthy breastfed newborn infants is not indicated unless the serum bilirubin
      level exceeds 15 mg/dl, but this value could be higher in the summer.

PMID- 9005730
TI  - [Usefulness of body surface cultures in newborns with early infection risk. Study
      of 735 neonates].
AB  - OBJECTIVE: Difficulty in the diagnosis of neonatal sepsis has lead to the
      practice of superficial cultures. The usefulness of this practice has been
      criticized repeatedly. PATIENTS AND METHODS: Results of 3881 cultures performed
      on 735 newborns (age < or = 48 hr) with early infection risk were reviewed. The
      types of samples chosen were urine (UR), gastric aspirate (GA), pharyngeal (PS),
      external ear (ES), umbilical swab (US), meconium (MC) and blood. BBV for sepsis
      for the different samples is calculated, as well as which ones better reflect
      vertical transmission. RESULTS: At the time of the study, 342 newborns (46.5%)
      were already colonized. Bacteria most frequently isolated were: E. coli (92), PCN
      staphylococci (85), enterococci (83) and S. agalactiae (70). Twenty-nine newborns
      had bacteriemia, with S. agalactiae being the leading cause (16). ES correlated
      best with positive blood cultures (83.3%). UR culture sensitivity was
      significantly lower than that of all other samples. The Highest PPVs were for GA,
      PS and US. NPV was high and similar for all samples (98-99%). ES and US best
      reflected vertical transmission (p < 0.0001). MC provided the highest number of
      positive mixed cultures, most of them difficult to evaluate. CONCLUSIONS: Body
      surface sample advantages are: 1) The possibility of discarding a vertically
      transmitted infection. 2) Quicker positive results than those in blood whenever
      liquid blood culture media are employed. 3) The possible identification of the
      etiologic agent when the mother has been given antibiotics intrapartum. 4).
      Information about dangerous colonization without infection. In order not to lose
      this useful information, but to save cost and effort, we advise that the number
      of surface cultures be reduced, keeping only ES and PS?

PMID- 9005731
TI  - [Diagnosis by echocardiography of a case of myxoma in the left ventricle].

PMID- 9005732
TI  - [Kartagener's syndrome: an infrequent cause of respiratory distress in neonates].

PMID- 9005733
TI  - [Syndrome of multiple neoplasia type IIB (MEN IIB): a case report].

PMID- 9005734
TI  - [Severe toxoplasmosis: two case reports].

PMID- 9005735
TI  - [Wolman's disease: a case report].

PMID- 9005736
TI  - [Cephalic trembling as a result of neonatal cerebral venous thrombosis].

PMID- 9005737
TI  - [Childhood pancreatitis as a consequence of hypertriglyceridemia associated with
      diabetic ketoacidosis].

PMID- 9005738
TI  - [Traumatic tearing of the diaphragm during infancy: four case reports].

PMID- 9005739
TI  - [Granulomatous angiitis of the central nervous system: a case report].

PMID- 9005741
TI  - [Internet and pediatrics 1996. Letter].

PMID- 9005740
TI  - [Jaundice in an infant].

PMID- 9005742
TI  - [The Albert scale of motor development: a new instrument for the evaluation of
      motor development. Letter].

PMID- 9005743
TI  - [Rashkind atrioseptostomia due to intraumbilical venous dissection. Letter].

PMID- 9005744
TI  - Primary treatment of acquired aplastic anemia: outcomes with bone marrow
      transplantation and immunosuppressive therapy. Seattle Bone Marrow Transplant
      Team.
AB  - BACKGROUND: Both immunosuppressive therapy and bone marrow transplantation are
      accepted treatments for patients with aplastic anemia. Choosing one of these
      therapies for a given patient depends not only on donor availability but also on
      such factors as patient age. OBJECTIVE: To compare survival rates and long-term
      complications after bone marrow transplantation or immunosuppressive therapy in
      patients with acquired aplastic anemia and to identify prognostic factors
      associated with improved survival. DESIGN: Center-based, retrospective analysis.
      SETTING: Referral center for patients with aplastic anemia. PATIENTS: 395
      patients with acquired aplastic anemia. INTERVENTION: Bone marrow transplant from
      an HLA-identical, related donor or immunosuppressive therapy. MEASUREMENTS:
      Kaplan-Meier survival curves, results of log rank tests, and cumulative incidence
      curves. RESULTS: Of 168 bone marrow transplant recipients, 89% had sustained
      engraftment. Forty-six patients developed grade II to IV acute graft-versus-host
      disease, and 68 developed chronic graft-versus-host disease that required
      therapy. Of 227 patients who received immunosuppressive therapy, 44% achieved a
      complete, partial, or minimal response. Fifty-four percent died or had no
      response to therapy. Actuarial survival at 15 years was 69% for bone marrow
      transplant recipients and 38% for patients receiving immunosuppressive therapy (P
      < 0.001). Improved survival was associated with having bone marrow
      transplantation as primary therapy, being younger, having no transfusion before
      transplantation, and having a higher absolute neutrophil count. Disease duration,
      year of therapy, sex, refractoriness to platelet transfusions, and previous
      treatment with androgens or corticosteroids did not significantly affect
      survival. CONCLUSIONS: Data from this center suggest that bone marrow
      transplantation may be preferred for younger patients with acquired aplastic
      anemia who have matched, related donors. Long-term survival is excellent for
      patients who respond to either form of therapy.

PMID- 9005745
TI  - Results of transplanting bone marrow from genetically identical twins into
      patients with aplastic anemia.
AB  - BACKGROUND: Aplastic anemia is caused by several diverse factors, including a
      lack of or defective hematopoietic stem cells, immune abnormalities, and
      disorders of the bone marrow microenvironment. The outcome of transplanting bone
      marrow from genetically identical twins into patients with aplastic anemia may
      help define how frequently these factors play a role in this condition.
      OBJECTIVE: To determine the outcome of transplanting bone marrow from genetically
      identical twins into patients with aplastic anemia. DESIGN: Observational study.
      SETTING: 31 centers participating in the international Bone Marrow Transplant
      Registry. PATIENTS: 40 patients with aplastic anemia who received bone marrow
      transplants from their genetically identical twins between 1964 and 1992.
      INTERVENTION: 23 patients received their first bone marrow transplant without
      pretransplantation conditioning; 17 received it after pretransplantation
      conditioning with cyclophosphamide alone or combined with other drugs or
      radiation. Six patients received post-transplantation immunosuppressive therapy
      with methotrexate, cyclosporine, and corticosteroids, alone or in combination.
      MEASUREMENTS: Outcomes of transplantation, including hematologic recovery and
      survival. RESULTS: Seven of 23 patients who received their first transplant
      without receiving conditioning had sustained complete hematologic recovery. One
      of 16 patients who did not have complete recovery after the first transplantation
      recovered after a second transplantation, which was not preceded by conditioning.
      The other 15 patients had two to five transplantations that were preceded by
      conditioning; in 13 patients, sustained bone marrow function was recovered.
      Twelve of 17 patients whose first transplantation was preceded by conditioning
      had sustained complete hematologic recovery. The likelihood of hematologic
      recovery was greater in patients who had conditioning before the first
      transplantation (P = 0.033). The actuarial 10-year survival rate for the 40
      patients was 78% (95% CI, 59% to 92%). The survival rate was higher in patients
      who did not have conditioning before the first transplantation (patients without
      conditioning, 87% [range, 65% to 99%]; patients with conditioning, 70% [range,
      47% to 89%]; P = 0.037). CONCLUSIONS: Most patients with aplastic anemia recover
      bone marrow function after receiving a transplant from a genetically identical
      twin. Pretransplantation conditioning may increase the chance of bone marrow
      recovery but does not seem to improve survival.

PMID- 9005746
TI  - Incidence of tuberculosis in the United States among HIV-infected persons. The
      Pulmonary Complications of HIV Infection Study Group.
AB  - BACKGROUND: The resurgence of tuberculosis in the United States is largely linked
      to the human immunodeficiency virus (HIV) epidemic. Despite this link, the
      epidemiology of tuberculosis and preventive strategies in patients infected with
      HIV are not completely understood. OBJECTIVES: To determine the incidence and
      predictors of tuberculosis in HIV-infected persons. DESIGN: Prospective,
      multicenter cohort study. SETTING: Community-based cohort of persons with and
      without HIV infection at centers in the eastern, midwestern, and western United
      States. PARTICIPANTS: 1130 HIV-seropositive patients without AIDS who were
      followed for a median of 53 months (814 homosexual men, 261 injection drug users,
      and 55 women who had acquired HIV through heterosexual contact). MEASUREMENTS:
      Delayed hypersensitivity response to purified protein derivative (PPD) tuberculin
      and mumps antigen, CD4 T-lymphocyte counts, and frequency of tuberculosis.
      RESULTS: 31 HIV-seropositive patients developed tuberculosis (0.7 cases per 100
      person-years [95% CI, 0.5 to 1.0]). The most important demographic risk factor
      was location (adjusted risk ratio for eastern compared with midwestern and
      western United States, 4.1 [CI, 2.0 to 8.4]). Tuberculosis occurred more
      frequently in persons with CD4 counts of less than 200 cells/mm3 (1.2 cases per
      100 person-years [CI, 0.7 to 1.9]) than in those with higher counts (0.5 cases
      per 100 person-years [CI, 0.3 to 0.8]). The rate of tuberculosis was highest
      among tuberculin converters (5.4 cases per 100 person-years [CI, 1.1 to 15.7]),
      lower among patients who were PPD positive at first testing (4.5 cases per 100
      person-years [CI, 1.6 to 9.7]), and lowest among patients who remained PPD
      negative (0.4 cases per 100 person-years [CI, 0.2 to 0.7]). Tuberculosis was not
      reported among persons who had PPD reactions of 1 to 4 mm. Compared with that of
      patients who tested positive for mumps, the risk for tuberculosis of those who
      tested negative was increased about sevenfold if they were PPD positive (P <
      0.03) and fourfold if they were PPD negative (P < 0.02). CONCLUSIONS: Incidence
      of tuberculosis was higher in the eastern United States, in patients with CD4
      counts of less than 200 cells/mm3, and in PPD-positive patients. Analysis of
      tuberculin reaction size supports the current interpretive criteria of the
      Centers for Disease Control and Prevention. Nonreactivity to mumps antigen
      indicated increased risk for tuberculosis independent of PPD response.

PMID- 9005747
TI  - Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy.
AB  - BACKGROUND: Loading doses of warfarin that are larger than those used for
      maintenance therapy are widely used in clinical practice, but they have never
      been prospectively evaluated. OBJECTIVE: To compare the effect of 5- and 10-mg
      loading doses of warfarin on laboratory markers of warfarin's anticoagulant
      effect. DESIGN: Randomized clinical trial. SETTING: Tertiary care teaching
      hospital. PATIENTS: 49 patients seen over a 5-month period with a target
      international normalized ratio (INR) of 2.0 to 3.0. INTERVENTION: Patients were
      randomly assigned to receive an initial dose of 5 or 10 mg of warfarin.
      Subsequent doses of warfarin were administered on the basis of dosing nomograms.
      MEASUREMENTS: INRs and levels of factors II, VII, IX, and X and protein C were
      measured daily for 5 days. RESULTS: 11 of 25 patients in the 10-mg group (44%
      [95% CI, 34% to 54%]) and 2 of 24 patients in the 5-mg group (8% [CI, 3% to 14%])
      had INRs greater than 2.0 at 36 hours (P = 0.005), at which time the factor VII
      levels were 27% (CI, 18% to 36%) in the 10-mg group and 54% (CI, 43% to 65%) in
      the 5-mg group (P < 0.001). In contrast, factor II levels were 74% (CI, 67% to
      81%) in the 10-mg group and 82% (CI, 73% to 93%) in the 5-mg group (P > 0.2). At
      60 hours, 9 of 25 patients in the 10-mg group (36% [CI, 17% to 54%]) and no
      patients in the 5-mg group had INRs greater than 3.0. At 84 hours, 15 of 24
      patients in the 10-mg group (63% [CI, 43% to 81%]) and 19 of 24 patients in the 5
      mg group (79% [CI, 62% to 95%]) had INRs between 2.0 and 3.0. Four patients in
      the 10-mg group and 1 patient in the 5-mg group received vitamin K for excessive
      prolongation of the INR. CONCLUSIONS: A 5-mg loading dose of warfarin produces
      less excess anticoagulation than does a 10-mg loading dose; the smaller dose also
      avoids the development of a potential hypercoagulable state caused by precipitous
      decreases in levels of protein C during the first 36 hours of warfarin therapy.

PMID- 9005748
TI  - Nonalcoholic steatohepatitis.
AB  - OBJECTIVE: To determine the clinical relevance of nonalcoholic steatohepatitis
      (NASH) and to review the available literature on the epidemiology, clinical
      features, histology, pathogenesis, clinical course, and management of this
      condition. DATA SOURCES: Pertinent articles in English identified through a
      MEDLINE search (1966 to the present) and the bibliographies of relevant articles.
      STUDY SELECTION: All studies, including case reports, evaluating the salient
      features and clinical profile of NASH. DATA EXTRACTION: Data were selected from
      all articles that fit the study selection criteria. DATA SYNTHESIS: Nonalcoholic
      steatohepatitis is a distinct clinical entity characterized by elevated plasma
      liver enzyme levels and liver biopsy findings that are identical to those seen in
      alcoholic hepatitis; patients with NASH, however, do not consume alcohol in
      quantities known to cause liver injury. Patients with NASH are typically obese,
      middle-aged women with asymptomatic hepatomegaly who are diabetic or
      hyperlipidemic and present with an unrelated medical problem. Analysis of liver
      biopsy specimens is the cornerstone of diagnosis; hepatic morphologic findings
      range from mild fatty degeneration and inflammation to cell degeneration,
      fibrosis, and cirrhosis with or without the presence of Mallory hyaline bodies.
      Elevated levels of free fatty acids in the liver are thought to be responsible
      for the development of steatohepatitis. Although NASH is most often a benign
      disease with an indolent course, patients with this condition occasionally
      develop cirrhosis, portal hypertension, and hepatic failure. In some cases, NASH
      may be reversed with weight reduction. CONCLUSION: Nonalcoholic steatohepatitis
      is an important differential diagnosis for asymptomatic patients with chronically
      elevated plasma liver enzyme levels, especially if obesity, diabetes, or
      hyperlipidemia are present. Analysis of liver biopsy specimens is necessary for
      diagnosis and must be done in all patients with unexplained abnormal liver
      function and negative results on a noninvasive workup. Prognosis is good in most
      patients. The precise role of weight reduction and ursodeoxycholic acid therapy
      in the favorable alteration of the natural history of this disorder needs to be
      addressed in large, well-controlled studies.

PMID- 9005749
TI  - Practical issues in physician-assisted suicide.
AB  - Support for the participation of physicians in the suicides of terminally ill
      patients is increasing, and the concrete effects on physician practice of a
      policy change with regard to physician-assisted suicide must be carefully
      considered. If physician-assisted suicide is legalized, physicians will need to
      gain expertise in understanding patients' motivations for requesting physician
      assisted suicide, assessing mental status, diagnosing and treating depression,
      maximizing palliative interventions, and evaluating the external pressures on the
      patient. They will be asked to prognosticate not only about life expectancy but
      also about the onset of functional and cognitive decline. They will need access
      to reliable information about effective medications and dosages. The physician's
      position on physician-assisted suicide must be open to discussion between
      practitioner and patient. Protection of the patient's right to confidentiality
      must be balanced against the need of health care professionals and institutions
      to know about the patient's choice. Insurance coverage and managed care options
      may be affected. All of these issues need to be further explored through
      research, education, decision making by individual practitioners, and ongoing
      societal debate.

PMID- 9005750
TI  - The role of medical necessity and cost-effectiveness in making medical decisions.
AB  - The term "medical necessity" is used ubiquitously in health care, but its meaning
      and implementation vary substantially among providers, payers, and patients. This
      ambiguity has led some to suggest that cost-effectiveness be used as a basis for
      decision rules. This paper presents an analytical framework that is familiar to
      clinicians and shows that medical necessity and cost-effectiveness do not provide
      deterministic rules for clinical decision making. First, 2 x 2 tables are used to
      show the tradeoff between the sensitivity and specificity of decision rules.
      Then, the example of asymptomatic abdominal aortic aneurysm is used to show that
      these tradeoffs can be seen as a continuum of decision rules on a receiver
      operating characteristic curve. Society can therefore choose a decision threshold
      on the basis of medical necessity that optimizes the number of lives saved or any
      other desired outcome, but the tradeoff between sensitivity and specificity
      cannot be avoided. Applying cost-effectiveness criteria may change the decision
      threshold because cost-effectiveness itself involves inherent tradeoffs that
      create additional ambiguity for clinical decisions. The conclusion is that
      decision rules based on medical necessity or cost-effectiveness should not be
      considered deterministic. Rather, decision rules are useful when they make
      assumptions explicit and specify tradeoffs so that clinicians, patients, and
      payers can make better decisions.

PMID- 9005751
TI  - The pre-Flexnerian reports: Mark Twain's criticism of medicine in the United
      States.
AB  - By the time Mark Twain was born, in 1835, the political forces of Jacksonian
      democracy had created an era of unregulated medical practice in the United
      States. Licensure laws were almost nonexistent, and any citizen could practice
      medicine. Regular ("allopathic") medicine was competing with at least two dozen
      other sects, including homeopathic, botanical, and hydropathic medicine. Although
      allopathy presented itself as the "scientific" branch of medicine and proclaimed
      the practices of the other sects to be "quackery," its therapies were aggressive
      and toxic and had no proven advantage over the treatments used by competitors.
      Through the efforts of the American Medical Association (AMA), allopathic
      medicine eliminated its competition by promoting the reestablishment of licensure
      laws in the late 1800s. In a continuation of the same endeavor, the AMA sought to
      identify weak and inadequate medical schools and commissioned Abraham Flexner to
      write the famous Flexner report of 1910 (the year of Mark Twain's death). Twain,
      an insightful political observer and social critic who was familiar with the
      competing medical systems and the medical politics of the 19th century,
      questioned the wisdom of limiting patients' medical options. He doubted the
      competence and intentions of physicians as a group even as he maintained
      confidence in the abilities of his own physicians. He was critical of the
      empirical medical practices used during his youth, but he saw hope in the new
      scientific orientation of medicine in the early 20th century. Twain's
      commentaries provide a unique perspective on pre-Flexnerian medicine in the
      United States.

PMID- 9005752
TI  - The care of dying patients.

PMID- 9005753
TI  - Autoimmunity and its treatment in aplastic anemia.

PMID- 9005754
TI  - DNA and the immune system.

PMID- 9005756
TI  - Prevention of venous thrombosis in knee arthroplasty.

PMID- 9005755
TI  - Babesiosis in Missouri.

PMID- 9005757
TI  - Prevention of venous thrombosis in knee arthroplasty.

PMID- 9005759
TI  - Any-willing-provider laws.

PMID- 9005758
TI  - Cost and the common cold.

PMID- 9005760
TI  - Perceptions by family members of the dying experience of older and seriously ill
      patients. SUPPORT Investigators. Study to Understand Prognoses and Preferences
      for Outcomes and Risks of Treatments.
AB  - BACKGROUND: Alleviating the problems faced by dying persons and their families
      has drawn substantial public attention, but little is known about the experience
      of dying. OBJECTIVE: To characterize the experience of dying from the perspective
      of surrogate decision makers, usually close family members (89%). DESIGN:
      Prospective cohort study. SETTING: Five teaching hospitals. PATIENTS: Persons who
      had one of nine serious medical conditions or were 80 years of age or older who
      died and for whom a surrogate decision maker completed an interview about the
      death. MEASUREMENTS: Medical records were reviewed and surrogate decision makers
      were interviewed. RESULTS: 4124 of 9105 seriously ill patients died (46%); 408 of
      1176 elderly patients died (35%). The patients' family members were interviewed
      after 3357 persons (73%) had died. Of 1541 patients who survived the enrollment
      hospitalization, 46% died during a later hospitalization. In the last 3 days of
      life, 55% of patients were conscious. Among these patients, pain, dyspnea, and
      fatigue were prevalent. Four in 10 patients had severe pain most of the time.
      Severe fatigue affected almost 8 in 10 patients. More than 1 in 4 patients had
      moderate dysphoria. Sixty-three percent of patients had difficulty tolerating
      physical or emotional symptoms. Overall, 11% of patients had a final
      resuscitation attempt. A ventilator was used in one fourth of patients, and a
      feeding tube was used in four tenths of patients. Most patients (59%) were
      reported to prefer a treatment plan that focused on comfort, but care was
      reported to be contrary to the preferred approach in 10% of cases. CONCLUSIONS:
      Most elderly and seriously ill patients died in acute care hospitals. Pain and
      other symptoms were commonplace and troubling to patients. Family members
      believed that patients preferred comfort, but life-sustaining treatments were
      often used. These findings indicate important opportunities to improve the care
      of dying patients.

PMID- 9005762
TI  - [Costs of video-laparoscopic surgery in the treatment of ovarian cysts].
AB  - The authors proceeded to point out the hospital stay costs and the operating-room
      costs of the operations for benign adnexal pathologies, especially concerning the
      ovarian cysts, after having introduced the laparoscopic technique. The highly
      costs, due to the laparoscopic surgical equipment, are compensated by the reduced
      hospital stay. The total unit cost for laparoscopic approach results lower then
      the total unit cost for laparotomic approach (L. 3.253.923 versus L. 4.662.892).
      If we consider that, in our local area, in 1993, 1212 operations were performed,
      with 5454 days of postoperative hospital stay, we could suppose that the
      laparoscopic approach affords higher savings. This cost estimation is important
      if we consider the diffusion of the mini-invasive procedures.

PMID- 9005761
TI  - [Costs of cholecystectomy after the arrival of video-laparoscopic surgery].
AB  - The authors proceeded to point out the hospital stay costs and the operating-room
      costs of the cholecystectomy after the introduction of the laparoscopic
      technique, underlining the higher economic advantages. The total unit cost for
      laparoscopic cholecystectomy, even if there are higher costs due to the surgical
      equipment, thanks to the mini-invasive approach and to the reduced hospital stay,
      results lower (17%) then the total unit cost for laparotomic cholecystectomy (L.
      3.982.489 vs. L. 4.825.300). Let us suppose that in the Emilia Romagna Region an
      80% of patients underwent to laparoscopic cholecystectomy and only a 20%
      underwent to laparotomic cholecystectomy: in this case there could be the
      economic savings of L. 3.777.478.902 and concerning the hospital stay there could
      be the savings of 17.928 days too. This cost estimation is important if we
      consider that the rate of cholecystectomy procedures, in our local area, per 1000
      inhabitants, increased from 2.29 in 1990 to 3.99 in 1992 (rate of increase: 74%).

PMID- 9005763
TI  - [Trans-umbilical cholecystectomy: a new laparoscopic cholecystectomy technique.
      Description of the technique and preliminary results].
AB  - The aim of videolaparo-cholecystectomy is to achieve a good results with minimal
      surgical trauma. Recently there has been an evolution of this technique toward
      the progressive reduction of trauma with an improvement of the results, also from
      the aesthetical point of view. In this article we describe our new videolaparo
      cholecystectomy technique. Trans-umbilical videolaparo-cholecystectomy represents
      a variant of the traditional technique. This new method allows the operation to
      perform with only two trocars positioned in the peritoneum cavity through only
      one umbilical incision. The technical innovation of this method consists of the
      substitution of the others trocars, utilized in the traditional technique, with
      an equal number of trans-parietal suspension wires. Up to now, we have given 95
      patients this kind of operation being successful in 67% of the cases. We think
      that this new technique, requiring as it does only standard laparoscopic
      instruments, is in accordance with the philosophy of mini-invasive surgery. The
      suspension wires are responsible for minimal bile spreading which is not an
      important complication if the surgeon performs an accurate and through cleaning
      of the abdominal cavity at the end of the surgical procedure. The patient better
      accepts this technique because of its better aesthetical results. In spite of
      this there should be more evaluable data about trans-umbilical videolaparo
      cholecystectomy especially about the incidence of post-operatory complications.

PMID- 9005764
TI  - [Celioscopic digestive surgery: from the explosion to a critical reflexion].
AB  - A critical review of laparoscopic digestive surgery indications is proposed.
      Patient's benefit by laparoscopy is to undergo the same procedure as by open
      surgery with identical security conditions but with less postoperative pain and
      an earlier recovery. Today laparoscopy in digestive surgery is mainly indicated
      in the fields of functional and benign diseases. Oncology seems for our team to
      stay a relative contra-indication as yet. Taken into account the future technical
      progresses, this 1996 state of the art is obviously only a temporary view of the
      technique before expected mutations.

PMID- 9005765
TI  - [Differentiated cancer of the thyroid: our experience].
AB  - The authors explain their experience about 136 patients affected by
      differentiated thyroid carcinoma. They compare different surgical procedure
      (total thyroidectomy vs conservative surgery). Although the surgical significance
      above the survival is discuss again, the authors, analysing the prognostic
      factors and the long term results, identify the total thyroidectomy maybe
      associated to lymphectomy and radioiodine therapy like the best treatment for
      this pathology.

PMID- 9005767
TI  - [Dunbar's syndrome: clinical reality or physiopathologic hypothesis?].
AB  - The authors report the cases of two patients presenting a symptomatic intestinal
      angina caused by median arcuate ligament compression. Arteriography demonstrates
      severe coeliac artery stenosis in both of them and a retrograde filling of the
      coeliac axis from the superior mesenteric artery branch collateral vessels. The
      patients became asymptomatic after surgical release of the celiac trunk by
      section of the median arcuate ligament of the diaphragm. At 2 and 3 years follow
      up, both patients report no further abdominal pain. Dunbar's syndrome is still a
      questionable subject; how can be a narrowing or an occlusion of the celiac artery
      semeiotically and clinically important? Some have proposed an ischemic base to
      explain the abdominal pain: the compression of the celiac trunk could be
      responsible of a celiac steal which results in shunting of blood from the
      superior mesenteric artery to the celiac distribution through the collateral
      system. There are very strong proofs that partial or even complete obstruction of
      the celiac artery should not lead to visceral ischemia such as: the rich
      collateral anastomosis of the celiac axis, the surgical ligation of the celiac
      axis performed without untoward consequences, the finding of asymptomatic celiac
      stenosis in the 49% of an arteriographic study, impossibility to formulate a
      consistent and rational for the surgical results. Shearing this view, few authors
      would prove that a stenotic type of the celiac artery is only a normal anatomic
      variant, refuting the existence of this syndrome.

PMID- 9005768
TI  - [Aorto-iliac aneurysms and associated gastrointestinal neoplasms. Treatment
      problems].
AB  - In patients affected by aortoiliac aneurysm the concurrent presence of a
      gastrointestinal tumor is a not infrequent occurrence which poses problems of
      therapeutic approach (one step operation or prior treatment of one of the two
      diseases; in the latter case definition of timing and sequence of the surgical
      treatment). Three cases are reported where an eclectic therapeutic approach has
      enabled satisfactory results. A patient with an isolated aneurysm of right
      hypogastric artery associated with rectal cancer was treated with percutaneous
      embolization of the aneurysm and subsequent excision of the tumor. In a patient
      with a neoplasm of the left colon and aortic aneurysm, the aneurysm was treated
      first and after about a month the tumor was resected. In a patient with gastric
      cancer and aortic aneurysm subtotal gastrectomy was first performed and
      subsequently, after about 3 months, the aneurysm was treated by extraperitoneal
      route. Even if an unidirectional approach cannot be defined, it is thought that
      the two-step treatment of the associated diseases is preferable. In the presence
      of non stenosed non bleeding colorectal tumors it seems more suitable to treat
      the aneurysm first (increased postoperative risk for rupture of the aneurysm;
      more difficult preparation of subrenal aorta in the presence of cicatricial
      outcomes of colonic surgery; persistence of perianastomotic infections after
      colonic resection). Gastric tumors should be treated first for their higher
      biological aggressiveness and unfeasible correct preoperative staging. In
      particular cases (single unilateral aneurysm of a hypogastric artery associated
      with gastrointestinal cancer), non surgical treatment of the vascular lesion
      (embolization during angiography) is the treatment of choice.

PMID- 9005769
TI  - [Entrapment syndrome of the popliteal vein: results of the surgical treatment].
AB  - Entrapment of the popliteal vein has been rarely reported. Purpose of the present
      study was to evaluate the long-term results of vein decompression in the
      popliteal vein entrapment syndrome. Between August 1986 and June 1994, 35
      patients (49 limbs) were operated on for popliteal vein entrapment syndrome at
      our Institution. There were 28 female and 7 male (mean age 44.5 +/- 13.5 years).
      Seven limbs had associated a popliteal artery entrapment syndrome. Twenty-three
      (49.6%) limbs presented with skin changes ascribed to venous disease.
      Preoperative diagnosis consisted on Doppler CW, Duplex Scan, venography and
      ambulatory venous pressure measurements. Surgical management consisted on the
      division of the anomalous structure causing entrapment. In 35 (71.4%) limbs
      subfascial ligation of perforating veins was associated. The patients were
      followed-up (mean 61 +/- 7 months) with venography and AVP. No deaths occurred
      and morbidity was 14.3%. Doppler CW and Duplex Scan were not accurate to diagnose
      the entrapment. Ambulatory venous pressure and venography accurately diagnosed
      the syndrome. Age and preoperative status did not affect long-term results (p =
      NS). Long-term operative success was negatively influenced by associated
      procedures for ligation of perforating veins (p < 0.03). Popliteal vein
      entrapment syndrome should be early diagnosed to prevent incompetence of
      perforating veins. Surgical treatment of cases not requiring ligation of
      perforating veins had a better long-term success rate. Treatment at later stages
      allows symptom amelioration but does not prevent the consequences of a long
      standing chronic venous disease.

PMID- 9005766
TI  - [Gynecomastia].
AB  - Gynaecomastia is a benign enlargement of the male breast commonly occurring in
      healthy adolescent boys and in adults (50 to 80 years old). It is a source of
      cosmetic and psychologic problems. The secondary forms usually require no therapy
      other than the removal of any identified inciting cause. Most of the idiopathic
      forms last only a few months and then gradually disappear. In secondary
      gynaecomastia and idiopathic forms present for more than 12 months a medical
      hormonal treatment often fails and the only therapy is surgery consisting in a
      subtotal subcutaneous mastectomy. In the last years the surgical treatment is
      often completed with suction lipectomy: this procedure reduces the surgical
      traumatism. The authors present their experience concerning 47 patients: 27 were
      surgical treated with subcutaneous subtotal mastectomy and 18 had an abjunctive
      liposuction treatment with good results.

PMID- 9005770
TI  - [Veno-venous crossover bypass according to Palma: our experience].
AB  - Four cases of Palma's operation (veno-venous cross-over bypass) performed from
      1986 through 1992 for occlusive venous disease are reported together with an
      extensive follow-up. After a synthetic review of the literature, the authors
      conclude that this operation should no more be considered an experimental
      procedure, even if a definite statement of its long-term usefulness (and
      therefore of the indication) is still lacking.

PMID- 9005771
TI  - [Our experience with Spigelio's hernia].
AB  - The authors present their experience about diagnosis and therapy of Spigelian
      hernia in five cases observed. Clinical examination is the foundation of the
      diagnosis and radiological findings (ultrasonography, colonic X-rays, CT and NMR)
      permit to exclude other pathologies which concern differential diagnosis. They
      suggest prosthetic repair, similar to the therapy of groin hernias, using a
      tension-free technique. This method of treatment avoids relapses and does not
      alter the functionality of muscular and aponeurotic apparatus.

PMID- 9005772
TI  - [An application of mini-invasive surface surgery: the thyroid].
AB  - Since its introduction, minimally-invasive surgery has been applied to structures
      contained in natural cavities such as abdomen, thorax and articulations. At
      present, its application to surface zones (plastic surgery) gives good results.
      For this reason, we tried to examine thyroid area through a video-assisted access
      in a 32 years old woman presenting a nodule with a diameter of about 1 cm,
      localized in the left parahistmic thyroid area. This approach allowed a good
      vision of the operative field. In our opinion, this technique could be useful
      especially to formulate the histological diagnosis of small thyroid nodules for
      whom the standard surgical biopsy should be considered too invasive.

PMID- 9005773
TI  - [Warthin's tumor. Description of 2 cases].
AB  - Warthin's tumor is a debated pathological condition. There are many controversies
      concerning this disease such as its origin (hereditary or acquired), its nature
      (whether neoplastic or no), its topographical relation with the salivary glands,
      its relationship with possible concomitant pathologies (dysmetabolic, infective,
      neoplastic, etc.), the problems of diagnosis and of differential diagnosis with
      all possible causes of cervical swelling, and also the problems of surgical
      treatment in relation to the possible involvement of the salivary glands. In this
      paper two clinical cases are described. The first one is characterized by a
      latero-cervical bilateral Warthin's tumor, apparently independent of the salivary
      glands, associated with rhinopharyngeal lymphatic hyperplasia and nodular colloid
      goiter. The second case is characterized by a latero-cervical uni-lateral
      Warthin's tumor, linked by a slender layer with the ipsilateral parotid gland,
      associated with breast cancer. Starting point from the discussion of these two
      cases, the Authors make remarks in order to answer some of the aforementioned
      questions.

PMID- 9005774
TI  - [Iatrogenic lesion of the thoracic duct in the neck. Presentation of a case].
AB  - Authors report a case of iatrogenic lesion of thoracic duct of the neck occurred
      during clearing the left latero-cervical zone for thyroid cancer. After reporting
      the relative unusuality of this complication, authors underline that in the
      literature there are always more frequent reports about lymphatic lesions in
      every district of the body due to more aggressive treatments. Although this case
      has been treated with a relatively simple operation (finding and binding the
      duct), treatment of these lesions is not always so simple and therefore knowledge
      of metabolic problems of these disorders, as well as the selection of the
      surgical strategy, should be always carefully evaluated for recovery of this
      disease.

PMID- 9005775
TI  - [Leiomyosarcoma of the duodenum: description of a clinical case].
AB  - Leiomyosarcoma of the small bowel is a rare malignant neoplasm, representing only
      the 8%-22% of duodenal malignancy. Diagnosis is difficult and useful is the TC
      scan of upper abdomen for the localization, extension and organ origin of the
      neoplasm. The authors report a clinical case of leiomyosarcoma of III portion of
      the duodenum, arose with intestinal hemorrhage, treated surgically with
      duodenocephalopancreatectomy, that nowadays represent the only therapeutic
      treatment for these tumors.

PMID- 9005776
TI  - [Intrahepatic dilation of the bile ducts. Particularity of a clinical case].
AB  - We report the case of a 71 years old male patient with a "simple" form of
      Caroli's syndrome. The "simple" form is less common than the form associated with
      congenital hepatic fibrosis. In this case the intrahepatic bile duct dilatation
      was confined to the segments V and VI, and intrahepatic lithiasis and
      cholelithiasis were associated. Usually, Caroli's syndrome remains asymptomatic
      for the first 20 years of the patient's life, sometimes longer, and in few cases
      for the patient's whole life. "Simple" asymptomatic Caroli's syndrome is
      generally unrecognized and in our own case it was an intraoperative finding.
      Patient's age, the presence of a hepatitis C and the absence of malignant changes
      discouraged us from performing a right hepatectomy and then a Roux-en-Y
      intrahepatic bile duct jejunal anastomosis was done. One year after the operation
      the patient is leading a normal life, and he is symptom-free.

PMID- 9005777
TI  - [Retroperitoneal Castleman's disease. Presentation of a clinical case].
AB  - Castelman disease (CD) is a rare lymphadenopathy that usually presents as a
      solitary, slow growing mass; its etiology is still unknown. The authors described
      a case of CD localized in the retro-pancreatic space. A 33-year old patient,
      female, underwent abdominal ultrasonography because of upper right abdominal
      pain. The ultrasound showed gallbladder stones and a mass of 4 cm in diameter
      behind the pancreatic head, modifying the shape of the inferior vena cava. The
      patient underwent surgical excision and histological examination showed a hyaline
      type of CD. In the 70% of the cases, the disease is located in the mediastinum,
      only in 14% of the cases in the retroperitoneal space. The case we report is a
      hyaline type of CD that is the most frequent histological type, constitutes 90%
      of the cases, occurs usually in the young population and after surgical excision
      has a very good prognosis. Different is the clinical behaviour of the plasma cell
      type of CD that has an aggressive and often fatal clinical outcome. The patient
      we treated is still free of any symptoms one year after the operation.

PMID- 9005778
TI  - The Camptothecins: From Discovery to the Patient. Proceedings of a conference.
      Bethesda, Maryland, February 7-10, 1996.

PMID- 9005779
TI  - [Use of ofloxacin in infections which do not readily respond to treatment].
AB  - The properties of ofloxacin such as a new mechanism of action, broad spectrum and
      high antimicrobial activity, 100-percent bioavailability and rapid penetration to
      the body tissues, etc. which defined the antibiotic high efficacy in the therapy
      of infections difficult for the treatment with other antibacterial drugs are
      presented. The intensive use of ofloxacin within the last years was no
      accompanied by an increase in the resistance of the main pathogens to it. High
      concentrations of ofloxacin provided in the nasa sinuses and the antibiotic broad
      spectrum including the majority of gram-positive and gram-negative microbes
      conditioned its high therapeutic efficacy in the treatment of chronic sinusitis
      and otitis. Successful treatment of tuberculosis resistant of other drugs with
      ofloxacin supplementing the standard 3-component combination of rifampicin,
      isoniazid and pyrazinamide was shown possible. By its bioavailability ofloxacin
      proved to be superior to ciprofloxacin and its oral dose of 200 mg was equivalent
      by the efficacy to the oral dose of 500 mg of ciprofloxacin. The usual regimen of
      the ofloxacin use in the treatment of severe infections was 400 mg intravenously
      twice a day. The further oral use in a dose of 400 mg once a day was possible
      after the infectious process stabilization.

PMID- 9005780
TI  - [Antimicrobial activity and action mechanism of ofloxacin].

PMID- 9005781
TI  - [Pharmacokinetic properties of ofloxacin (review of the literature].

PMID- 9005783
TI  - [Clinico-pharmacologic aspects of the use of ofloxacin].
AB  - Ofloxacin was used in the treatment of 124 patients with bronchopulmonary
      diseases, the diseases of the biliary system and other infectious inflammatory
      diseases of the internal organs. The microbiological and pharmacokinetic indices
      as well as the immune status were investigated. The drug proved to be efficient
      in the treatment of 78.9 per cent of the cases. The pharmacokinetic indices were
      evident of the fact that the treatment of severe cases should be started with the
      drug intravenous administration. Ofloxacin had no negative effects on the immune
      status.

PMID- 9005782
TI  - [Mechanisms of resistance to quinolones and current level of sensitivity of
      clinically important microorganisms to ofloxacin].
AB  - The data on the mechanisms of microbial resistance to fluoroquinolones are
      presented. Comparison of the susceptibility levels of the microorganisms isolated
      on the territory of Russia showed that among the gram-negative opportunistic
      isolates 84 per cent was susceptible to ofloxacin, 45 per cent to
      ampicillin/sulbactam, 70 per cent to cefotaxime, 80 per cent to ceftazidime, 85
      per cent to amikacin and 62 per cent to gentamicin. Among the Salmonella,
      Shigella and Vibrio cholerae isolates no strains were resistant to ofloxacin.
      Among the Salmonella isolates from patients more than 30 per cent was resistant
      to ampicillin, chloramphenicol, trimethoprim/sulmethoxasole and tetracycline.
      Among the Salmonella isolates 65 to 90 per cent was resistant to the antibiotics.
      Among the V.cholerae isolates 59 per cent was resistant to
      trimethoprim/sulmethoxasole.

PMID- 9005784
TI  - [Fluoroquinolones--current value in antibacterial therapy, outlook for
      development].

PMID- 9005785
TI  - [An attempt to use ofloxacin in patients with mucoviscidosis].
AB  - The literature data and the data of the authors on the pathogenesis and
      pathogenetic and etiotropic therapy of mucoviscidosis are presented. The use of
      ofloxacin as an antibacterial agent in the complex treatment of mucoviscidosis is
      considered expedient. The drug was administered intravenously in a dose of 400 mg
      twice a day for 5 days followed by the oral use of the drug in the form of
      tablets according to the same scheme. The microbiological investigation of the
      sputum specimens revealed diagnostically significant titers of Pseudomonas
      aeruginosa, Staphylococcus aureus and Klebsiella spp. The isolates except for one
      case (Ps.aeruginosa) were susceptible to ofloxacin. The treatment with ofloxacin
      in accordance with the above scheme resulted in a rapid improvement of the
      patient state: the intoxication lowered, the expectoration and the sputum
      viscosity decreased, the body temperature normalized by the 5th day. The drug
      tolerance after the intravenous and enteral administration was good. The
      intravenous injections of ofloxacin induced a 1.5-fold increase in the intensity
      of the neutrophil oxygen burst. After the drug enteral administration there was
      observed a 2-fold increase the intensity of the neutrophil oxygen burst.

PMID- 9005786
TI  - [Clinical and pharmacokinetic evaluation of ofloxacin under various regimens of
      administration in patients with bronchopulmonary infections].
AB  - Ofloxacin was used in the treatment of 24 patients with chronic bronchitis or
      pneumonia at the background of chronic bronchopulmonary and cardiovascular
      diseases. The drug was administered in accordance with 2 regimens: orally in a
      dose of 400 mg once a day (group I) and intravenously in a dose of 200 mg twice a
      day for 2 to 4 days followed by the drug oral use in the same dosage for 6 to 8
      days (group II). The trial included comparison of the treatment efficacy by a
      complex of clinicobacteriological indices, estimation of the drug
      pharmacokinetics under the two regimens and prediction of the drug concentrations
      in blood with the mathematical models. High clinical and bacteriological
      efficacies of ofloxacin were shown under both the regimens. The pathogen
      eradication under both the regimens was observed in 61.5 and 72.7 per cent of the
      cases in groups I and II respectively. Dependence of the ofloxacin blood
      concentrations in the patients on the dosage regimen was detected. The
      pharmacokinetic studies demonstrated the possible prediction of the drug blood
      concentrations after the multiple administrations based on the calculated
      parameters.

PMID- 9005787
TI  - [Stepdown ofloxacin therapy in bronchopulmonary diseases].
AB  - Ofloxacin was used in the treatment of 15 patients (12 with pneumonia and 3 with
      aggravated chronic bronchitis). The drug was administered at first intravenously
      in a dose of 200 mg twice a day for 3 days and then orally in the same dosage.
      Before the treatment Streptococcus, Pneumococcus and Klebsiella strains were
      isolated from the sputum specimens (12, 2 and 2 cases respectively). All the
      isolates except for 3 Streptococcus strains were susceptible to ofloxacin. After
      the treatment the recovery and improvement were stated in 14 patients. One
      patient with pneumonia at the background of chronic bronchitis due to resistant
      Streptococcus strains was excluded from the trial since the treatment with
      ofloxacin failed. 252 isolates from the sputum specimens of the patients with
      pulmonary affections were subjected to the laboratory tests and high activity of
      the fluoroquinolone against the gram-positive and gram-negative organisms was
      shown. The isolates were often resistant to tetracycline. It was concluded that
      the use of ofloxacin in the successive therapy of patients with pulmonary
      diseases was expedient.

PMID- 9005789
TI  - [Chronic osteitis--modern therapy].
AB  - The results of the clinical trials with ofloxacin in the treatment of osteitis
      are presented. The drug was used according to 3 regimens: 200 mg thrice a day,
      200 mg twice a day and 400 mg once a day for 6 to 24 months. The disease
      diagnosis was based on the bacteriological investigation of the biopsy specimens
      and hemocultures. The isolates were shown to be susceptible to ofloxacin. The
      majority of the patients (78 per cent) was treated with ofloxacin after the
      preliminary surgical operations. The treatment was started with the ofloxacin
      intravenous administration in a dose of 400 mg followed by the drug oral use in
      the same dose once a day for at least 14 days. The most frequent causative agents
      were: Staphylococcus aureus (52 per cent of the cases) and Staph.epidermidis
      (13.7 per cent of the cases) which were eradicated in 91.7 and 93.9 per cent of
      the cases respectively when the ofloxacin MICs were 0.26 and 0.22 mg/l
      respectively. The number of the gram-negative isolates on the whole amounted to
      72.56 per cent and that of the gram-negative isolates amounted to 27.46 per cent
      of all the pathogens. As for the latter Pseudomonas aeruginosa and Enterobacter
      spp. were the most frequent (11.14 and 5.4 per cent respectively). The
      eradication of the pathogens amounted to 80.6 and 94.43 per cent respectively
      when the drug MICs were 1.78 and 0.42 mg/l respectively. The regimen with the
      drug oral use in a dose of 400 mg once a day proved to be the most expedient. It
      provided the complete therapeutic effect, minimum cost and maximum comfort for
      the patients.

PMID- 9005788
TI  - [Clinical trials of ofloxacin in sequential use (intravenous and oral) in
      patients with serious hospital infection].
AB  - Fifteen patients with severe hospital infections such as postoperative pneumonia
      or intraabdominal sepsis were treated with ofloxacin in a dose of 400 mg once a
      day for 7 to 14 days (11 days at the average). The drug was administered
      intravenously for the first 3-5 days and then orally till the end of the
      treatment course. The clinical effect was observed in 14 patients (93 per cent)
      and the positive bacteriological effect was stated in 11 out of 13 patients (85
      per cent). Before the treatment 18 microbial cultures were isolated from the
      patients. 94 per cent of them was susceptible to ofloxacin. The isolates of
      Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were the most
      frequent. The treatment resulted in the eradication of 15 cultures (83 per cent).
      The adverse reactions were observed in 3 patients but only in 1 of them they were
      for certain due to the drug use. All the adverse reactions were insignificant or
      moderate and did not require the treatment discontinuation. The trials showed
      that ofloxacin was a highly efficient agent useful in the empirical monotherapy
      of patients with severe hospital infection.

PMID- 9005790
TI  - [A method of sequential (intravenous and oral) use of ofloxacin in the treatment
      of patients with infections of organs of the peritoneal cavity].
AB  - Clinico-laboratory estimation of the efficacy and tolerance of ofloxacin used in
      succession, at first intravenously and then orally, in the treatment of 15
      patients with infection of the abdominal cavity was performed. It was shown that
      after the use for a period of 10 years ofloxacin preserved its high antimicrobial
      activity against gram-positive and gram-negative organisms with multiple drug
      resistance and remained superior to the majority of broad spectrum antimicrobial
      agents by the number of susceptible isolates. The successive use of ofloxacin
      proved to be highly efficient. The total efficacy of the drug amounted to 80
      percent and no side effects were recorded. The analysis of the microbiological
      state of the antiinfectious resistance system (AIRS) showed that the dysbiotic
      lesions on the mucosa of the upper respiratory tracts and large intestine
      detected in all the patients before the treatment with ofloxacin remained after
      the treatment. However, a change in the microflora responsible for dysbacteriosis
      was observed. The investigation of the immunological status of the AIRS suggested
      that the good and satisfactory results of the therapy with ofloxacin could to a
      significant extent be due to the proportion of the active neutrophils.

PMID- 9005791
TI  - [Ten-year experience with the use of ofloxacin in reconstructive surgery].
AB  - The data on the use of ofloxacin in more than 300 surgical patients for the last
      10 years were analyzed. The results showed that despite the wide clinical use of
      ofloxacin in the prophylaxis and treatment of postoperative complications the
      drug remained highly active against the predominating majority of microbes
      causing surgical infections. Therefore, the broad spectrum, high bactericidal
      activity and optimal pharmacokinetics with the high biovailability at the level
      of 95 to 100 per cent provided the use of ofloxacin as a highly efficient agent
      in the treatment of postoperative infectious complications in surgical
      inpatients.

PMID- 9005792
TI  - [Ten-year experience with the use of ofloxacin in the treatment of wound
      infection].
AB  - The experience with ofloxacin used for 10 years from 1986 to 1995 in the complex
      therapy of 208 patients with wound infection complicated in 51 patients (24.5 per
      cent) by respiratory tract infection such as purulent tracheobronchitis or
      pleuropneumonia was generalized. In 28 patients (13.5 per cent) persistent
      bacteriuria not susceptible to the routine drugs was stated. The clinical and
      bacteriological efficacies of ofloxacin in the group of the patients with
      noncomplicated purulent wounds of the soft tissues amounted to 85-91 and 74-80
      per cent respectively. In the group of the patients with wound infection
      complicated by respiratory or urinary tract infection the clinical and
      bacteriological efficacies equaled 94-100 per cent. The appetite disorder,
      epigastric pain or nausea were rare. Only in 3 cases the adverse reactions
      required the treatment discontinuation. Despite the use of ofloxacin for many
      years, the susceptibility of the main causative agents of surgical infections to
      the drug remained high: Staphylococcus epidermidis 93.3 per cent, Staph.aureus
      94.5 per cent, Pseudomonas aeruginosa 96.5 per cent, Escherichia coll 100 per
      cent, Proteus spp. 100 per cent, Enterobacter spp. 100 per cent, Acinetobacter
      spp. 82.3 per cent and Klebsiella spp. 88.8 per cent. The successive use of
      ofloxacin, at first intravenously for 3-5 days and then orally in the form of
      tablets for 3-5 days, in the treatment of 15 patients with wound infections of
      various genesis and localization subjected to osteoplastic reconstructive
      operations provided positive effects in all the cases and was economically
      advantageous.

PMID- 9005793
TI  - [Ofloxacin in comprehensive treatment of infections in burn patients].
AB  - The experience with ofloxacin in the prophylaxis and treatment of infected burn
      wounds in 40 patients was investigated. High clinical and microbiological
      efficacy of the drug was stated (82.5 and 83 per cent respectively). The highest
      efficacy of ofloxacin was observed when the burned area did not exceed 25 per
      cent of the body surface. It was concluded that the prophylactic use of the drug
      during acute burn toxemia was not expedient.

PMID- 9005794
TI  - [Comparative evaluation of the effectiveness of ofloxacin in comprehensive
      treatment of acute inflammatory diseases of the uterus and uterine appendages].
AB  - Ofloxacin was used in the complex therapy of acute inflammatory diseases of the
      uterus and uterine appendages. The patients were divided into 2 groups. Group 1
      included 15 patients treated with ofloxacin in a dose of 200 mg administered
      intravenously twice a day for 4 to 6 days. After that period the drug was used
      orally in the same dosage for 4 to 6 days. Group II was control and included 20
      patients treated with some other broad spectrum antibiotics such as amplox,
      gentamicin and 3rd generation cephalosporins. Because of the disease severity in
      33 patients they were subjected to surgical operations. The clinical recovery was
      stated in all the 35 patients. However, by a complex of the indices the efficacy
      of ofloxacin was higher than that of the other antibiotics. An improvement of the
      general state (no headache or weakness and normalization of the body temperature)
      was observed in the patients of group I 2-3 days earlier as compared to the
      patients of group II. Purulent discharge from the genitalia ceased 3-4 days
      earlier in the patients of group I by comparison with the control patients. Good
      tolerance of ofloxacin was observed and no severe adverse reactions were
      recorded.

PMID- 9005795
TI  - [Clinical experience with the use of ofloxacin in infections of the upper and
      lower urinary tracts: demonstrations of the results of clinical trials].
AB  - The efficacy and safety of ofloxacin in the treatment of upper and lower urinary
      tract infections were studied with the drug use according to 4 regimens by
      comparison with nitrofurantoin in the treatment of lower urinary tract infections
      and trimethoprim/sulfamethoxazole in the treatment of upper urinary tract
      infections. Ofloxacin was used in doses of 100 to 200 mg once or twice a day for
      3, 5 and 10 days. In a separate group of 30 female patients with frequent
      recurring noncomplicated lower urinary tract infections ofloxacin was used in a
      dose of 50 mg once a day for 6 months. Ofloxacin was shown to be highly efficient
      in the treatment of medium and severe infections of the upper and lower urinary
      tracts. The following regimens were recommended: 200 mg once a day in the
      treatment of medium urinary tract infections, 100 mg twice a day for 3 to 7 days
      in the treatment of severe infections of the lower urinary tract and 200 mg twice
      a day for 7 to 10 days in the treatment of severe upper urinary tract infections.
      The use of ofloxacin in a daily dose of 50 mg for 6 months proved to be efficient
      in the treatment of frequent acute recurring infections of the urinary tracts.

PMID- 9005796
TI  - [Comprehensive treatment with ofloxacin in pyo-inflammatory urologic diseases].
AB  - Fifteen patients with various forms of pyelonephritis and chronic cystitis were
      treated with ofloxacin. The drug was used in the complex antiinflammatory and
      detoxification therapy and in cases with indicated hemotransfusion. Ofloxacin was
      administered intravenously during the first days of the treatment with its later
      oral use. High efficacy of ofloxacin was observed in the patients with acute
      purulent renal affections accompanied by pyo-intoxication when the treatment was
      started with the drug parenteral administration.

PMID- 9005797
TI  - [Outlook and experience in using ofloxacin in urology].
AB  - Ofloxacin was used in the empirical and etiotropic therapy of patients with
      severe urinary tract infection. The trial was based on the previous experience
      with ofloxacin in the treatment of various forms of urological infection with
      determination of the pathogen susceptibility and study of the drug
      pharmacokinetics in patients with normal and impaired renal function. For the
      first 3 to 5 days in the present study ofloxacin was administered in a dose of
      200 mg twice a day followed by its oral use in the same dosage for 3 to 5 days.
      The treatment schemes were corrected by the bacteriological findings (mainly when
      Pseudomonas aeruginosa strains were isolated). The results of the treatment of
      more than 200 patients showed that ofloxacin was highly efficient. By the
      clinical and bacteriological indices the drug proved to be efficient in 96 and 88
      per cent of the cases respectively. In the treatment of patients with
      noncomplicated urinary tract infection good results (the clinical and
      bacteriological efficacies of 96 and 88 per cent respectively) were observed when
      ofloxacin was used orally in a single dose of not more than 400 mg once a day for
      3 to 5 days. In the patients with chlamydiosis the drug was used in the same
      dosage for 10 days. Ofloxacin was also shown to be highly efficient when used
      prophylactically in transurethral surgical operations on the prostate and in open
      urological operations.

PMID- 9005798
TI  - [Treatment of Flexner's dysentery with ofloxacin].
AB  - Twenty four patients with dysentery due to Shigella flexneri2a and 1 patient with
      mixed infection (acute dysentery due to Sh.flexneri 2a+group B salmonellosis)
      were treated with ofloxacin. The patients were divided into 4 groups. In group I
      ofloxacin was administered intravenously in a dose of 200 mg twice a day followed
      by its oral use in the form of tablets in a dose of 200 mg twice a day for 5 to 6
      days. In group II ofloxacin was used orally in the form of tablets in a dose of
      200 mg once a day in the morning for 5 to 7 days. In group III ofloxacin was used
      in the same dosage but in combination with some other antibiotics. In group IV
      the patients were treated with antibiotics except for ofloxacin. High efficacy of
      ofloxacin was observed with all the regimens. In the patients treated with
      ofloxacin rapid improvement of the patient state (normalization of the body
      temperature by the 2nd or 3rd day) and complete eradication of the pathogens were
      recorded. Ofloxacin was superior by the efficacy to the other antibiotics.

PMID- 9005799
TI  - [An attempt to use ofloxacin in the treatment of acute intestinal infections].
AB  - The efficacy of ofloxacin in the treatment of acute intestinal infection was
      estimated. The trial included 31 patients: 27 with acute dysentery and 4 with
      salmonellosis. In all the patients the diagnosis was confirmed bacteriologically.
      The drug was used in a dose of 200 mg twice a day for 5 days. During the first 2
      days ofloxacin was administered intravenously and during the following 3 days it
      was used orally. In the treatment of 3 patients with medium diseases ofloxacin
      was used orally during the first 3 days in a dose of 200 mg twice a day in
      combination with intravenous drop-wise infusion of the drug in a dose of 200 mg
      twice a day. In the chronic carriers ofloxacin was used in a dose of 400 mg twice
      a day for 5 days. Good efficacy of the drug was observed in the treatment of
      acute dysentery evident from the disease rapid favourable time course: by the 2nd
      day the body temperature lowered and the abdominal pains alleviated and by the
      4th to the 6th days the stool came to the normal. Dysbiotic changes in the
      patients treated with ofloxacin were less pronounced by comparison with those
      after the treatment with other antibacterial drugs. Ofloxacin provided rapid
      eradication of Chlamydia in the faces and the recovery from chlamydiosis as a
      concomitant disease of acute dysentery in 8 patients.

PMID- 9005800
TI  - [Ten-year experience with the use of ofloxacin (Tarivid*). New treatment
      regimens].

PMID- 9005801
TI  - [Joy riding and dyssocial behavior. A comparative study based on 84 members of a
      delinquent group].
AB  - Joy riding is the technical term for a specific behavioral pattern consisting of
      stealing a car without money-making purposes but in order to take it for fast and
      exciting rides, partially in combination with alcohol or drug consumption. In
      several cases this behavior can show addiction-like traits. American studies from
      earlier decades have shown that Joy riding seems to be a typical teenage offense
      committed by youths stemming from orderly social backgrounds, showing basically
      prosocial attitudes and seldom ending up in criminal careers. However, the
      present study provides evidence that Joy riding can also be part of an antisocial
      lifestyle. The characteristics of the joy riders examined in this trial differed
      just gradually from the control group of juvenile delinquents. It remains open a
      question, whether the differences found between our sample and American joy
      riders are due to sociocultural factors or rather are a consequence of different
      selection modes.

PMID- 9005802
TI  - [Unusual motivation in double suicide of a lesbian couple. Phenomenology,
      psychodynamics and influence of contemporary values].
AB  - Double suicides are regarded as uncommon phenomena. In particular, homosexuals
      are very rarely involved. It is reported on the unusual motivation of a dual
      suicide by hanging among two 20-year-old lesbian women. Due to abnormal psychic
      development and mutual induced reaction the thought of dying together and being
      reborn jointly in one person (a contemporary actor) arose. These ideas were
      influenced by spiritism and metempsychosis. The case is well-documented by diary
      records and will be discussed under phenomenological and psychodynamic aspects.
      Typical and atypical criteria of double suicides are featured.

PMID- 9005803
TI  - [Phenomenology of kicking and kicking to death].
AB  - 28 autopsy cases with injuries due to blunt trauma comprising kicking or stamping
      on the victim are analysed for characteristics of the victims, the perpetrator
      and the assault as well as for the injury pattern. Emphasis is put on patterned
      contusions which in cases of medium impact reflect the characteristics of the
      footwear that made them as a mirror image.

PMID- 9005804
TI  - [Discovery of a human hand?].
AB  - We report on an unusual bone finding in the northeast of Germany. The "human hand
      of a child" was identified as the left foot of a baboon.

PMID- 9005805
TI  - [Fatal chloroform poisoning with subsequent crime].
AB  - Criminal poisoning using chloroform to commit another crime has been published
      infrequently. A case of a 52-year-old robbery victim is reported. The man was
      found dead in a park with a yellow duster in a very close position to his nose
      and mouth. Autopsy revealed no serious pathological findings to explain the
      death. Because of the suspected violent application of a volatile compound and to
      avoid a loss of tissue concentration the samples for toxicological investigations
      were taken at the very beginning of the autopsy. The detailed results showed that
      a chloroform poisoning has been the only cause of death.

PMID- 9005807
TI  - ["Depilation" by micro-algae?].
AB  - Itching, reddening and depilation of body hairs was reported by swimmers in the
      Attersee-lake in Austria. Initially, an environmental crime was suspected.
      However, further investigations showed that a biological cause was probably
      responsible for these symptoms. The accrustations found on body hairs turned out
      in the scanning electron microscope to be dried mucus containing numerous
      diatoms. The prevailing micro-algae were identified as Cyclotella comensis. Thus,
      although the phenomenon had a natural, harmless cause, it may happen again given
      the appropriate environmental conditions.

PMID- 9005806
TI  - [Detection of fluid in paranasal sinuses as a possible diagnostic sign of death
      by drowning].
AB  - A total of 387 cases of drowning in fresh water were investigated for the
      occurrence of liquid in sinus sphenoidalis and both left and right sinus
      maxillaris. About 75 per cent of the victims had positive findings of liquid in
      these cavities. This kind of investigation can be an auxiliary method in
      diagnosis of drowning.

PMID- 9005808
TI  - [Expert insect identification in cases of decomposed bodies].
AB  - We report two cases in which putrefied corpses were found in the state of massive
      myasis (colonisation of files); in one case, also beetles could be collected.
      Case 1:A human corpse was found four months postmortem exposed freely near a
      railway embankment (suicide, known heroin user). Masses of jumping cheese skipper
      fly larvae were found on the corpse and bred for identification subsequently.
      Furthermore, several beetles were found. Case 2: Three months after removal of a
      corpse found dead for one and a half month in fall/wintertime in a flat, green
      blue blowflies and their larvae were seen constantly in the now completely empty,
      disinfected flat and in a flat being situated in the floor below. Larvae hid
      behind vertical floor ledges and wall-on-walls made of plaster and rested in
      diapause until temperature increased.

PMID- 9005809
TI  - From chloroquine to antineoplastic drugs? the story of antibacterial quinolones.
AB  - Chemotherapy has not only proved valuable in treating many diseases but the
      history of discovery of some drugs makes exciting reading. The aim of this
      article is to outline one such story.

PMID- 9005810
TI  - Benzimidazole-type glycine antagonists: the role of the ring nitrogen atoms.
AB  - Several derivatives of 1H-benzimidazole-2-carboxylic acid (BICA, 2a) were tested
      in vitro in comparison to 1H-indole-2-carboxylic acid (ICA, 1e) for their ability
      to displace [3H]glycine from rat hippocampal membranes. Compound 2a was 8 times
      more potent than 1e (Ki 5.3 microM, as compared to 42 microM). However,
      introduction of a carboxymethyl group or a corresponding ester at position 3 had
      no positive effect on the potency of 2a, while this type of structural
      modification increased the potency of 1e significantly. Nevertheless, 1
      carboxymethyl-BICA (2b) displaced [3H]glycine with similar potency as the
      corresponding 3-carboxymethyl-ICA 1c, indicating that also a nitrogen atom
      lacking a hydrogen atom can be engaged in glycine receptor interaction. N
      Methylation strongly reduced the potencies of both BICA and ICA derivatives.

PMID- 9005811
TI  - "Vinylogs" and "acetylenylogs" of beta-adrenergic agents.
AB  - Vinylogous (Groups III and V) and acetylenologous (Group IV) analogs of the
      classical beta-adrenergic agents--stimulants and blockers--were prepared in order
      to evaluate the effect of degree of saturation, position of unsaturation and
      rigidity of the chain linking the aromatic ring and the amino containing
      functional group on biological activity. Derivatives from Group III, which
      represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II, retained beta 1
      adrenoceptor antagonist activity albeit substantially less potent (50-200-fold)
      than that possessed by their aryloxy counterparts. Consistent with the SAR for
      Group II compounds, substitution at position 2 of the aromatic ring yielded the
      most potent antagonists (5a, 5d, 5g), with KB's ranging from 73-93 nM while 3,4
      dichloro substitution (5e) markedly reduced antagonist potency (KB = 2,400 nM).
      Agonist activity was also noted for 5b and 5d, suggesting that these compounds
      may be best classified as partial agonists. Representatives from Groups IV and V
      were inactive as antagonists at the beta 1-adrenoceptor confirming the importance
      of the spatial relationship between the hydroxyl and the amino nitrogen.

PMID- 9005812
TI  - Proton NMR conformational analysis of cyclic beta-casomorphin analogues of the
      type Tyr-cyclo[N omega-D-Orn-Xaa-Yaa-Gly-].
AB  - A conformational study of the cyclic beta-casomorphin-5 analogues H-Tyr-cyclo[-D
      Orn-2-Nal-Pro-Gly-] (1) (mu-selective agonist; 2-Nal = 2 naphthylalanine), H-Tyr
      cyclo[-D-Orn-2-Nal-D-Pro-Gly-] (2) (mixed mu agonist/delta antagonist) and H-Tyr
      cyclo[-D-Orn-Phe-D-Pro-Gly-] (3) (highly potent mu and delta agonist) has been
      carried out using 1H NMR spectroscopy. A complete assignment of the proton
      resonances of the three pentapeptides has been achieved. Compound 1 was shown to
      exist in two conformations, a major one (90%) characterized by a cis amide bond
      between 2-Nal3 and Pro4, and a minor one (10%) showing cis amide bonds both
      between D-Orn2 and 2-Nal3 and between 2-Nal3 and Pro4. Peptides 2 and 3 each
      showed only one conformer with all-trans peptide bonds in both cases. Temperature
      dependence studies of the amide proton chemical shifts indicated the existence of
      several intramolecular hydrogen bonds in the case of compounds 2 and 3 but not in
      the case of peptide 1. The backbone conformations of 2 and 3 were found to be
      similar, both being characterized by two consecutive gamma turns around the D
      Pro4 and D-Orn2 residues, respectively, and by a D-Orn2-CO<--HN delta-D-Orn2
      hydrogen bond. Altogether, the overall backbone conformation and the preferred
      side chain conformation were found to be roughly similar for the three title
      peptides. For all three compounds a close proximity between the aromatic moiety
      of the 3-position residue (2-Nal or Phe) and the D(or L)-Pro4 residue was
      established on the basis of ROESY experiments. The examination of low energy
      conformations obtained in molecular modelling studies by taking into account the
      various experimentally found NMR parameters (NOEs, vicinal H,H coupling
      constants, torsion angles, H-bonds) led to proposals of the solution conformation
      for each peptide. These conformations are in close agreement with a pharmacophore
      model for mu opioid receptor binding compounds.

PMID- 9005813
TI  - The role of (Z)-2,3-didehydrophenylalanine and phenylalanine C-terminal residues
      in determining the chemotactic activity of formylpeptides.
AB  - Several formylpeptides, analogs of the chemotactic agent HCO-Met-Leu-Phe-OMe,
      having the HCO-Xaa-Leu-delta ZPhe-OMe and HCO-Xaa-Leu-delta ZPhe-Phe-OMe
      structures (delta ZPhe = (Z)-2,3-didehydrophenylalanine), have been synthesized.
      The biological activity of these ligands has been determined on human neutrophils
      and compared to that of the corresponding HCO-Xaa-Leu-Phe-OMe derivatives not
      containing the unsaturated residue. The replacement of the C-terminal Phe with
      delta ZPhe causes, in all the examined tripeptides, the loss of any biological
      activity. On the other hand, the introduction into the delta ZPhe containing
      models of an additional C-terminal Phe residue leads to the formyltetrapeptides
      HCO-Xaa-Leu-delta ZPhe-Phe-OMe which show a biological activity very similar to
      that exhibited by the corresponding HCO-Xaa-Leu-Phe-OMe analogues.

PMID- 9005814
TI  - Activity of 2-azaspiro[4.5]decane-6-carboxylates as GABA-uptake inhibitors.
AB  - Novel GABA analogous spirocyclic amino acid esters 7a-d and 8a-d were prepared
      and investigated for interaction with GABA-A and GABA-B receptors as well as the
      GABA uptake system. Starting from known bromoethyl lactones 1 or 2 and
      arylalkylamines spirocyclic hydroxyalkyl lactams 3a-d and 4a-d were obtained and
      reduced by LiAlH4 to yield spirocyclic hydroxymethyl pyrrolidines 5a-d and 6a-d.
      Oxidation by Jones reagent followed by subsequent esterification gave the title
      compounds 7a-d and 8a-d which represent conformationally restricted analogues of
      GABA. Whereas the new spirocyclic amino acid esters 7a-d and 8a-d showed no
      activity at GABA receptors they proved to be active as GABA uptake inhibitors. An
      examination of the relationship between structure and GABA uptake inhibition
      revealed a strong dependence of activity upon the length of the alkyl chain in N
      arylalkyl substituents and upon the ring size of underlying spirocyclic system.

PMID- 9005815
TI  - Antimicrobial effects of oligoamines.
AB  - Twenty-four oligoamines belonging to six (1-6) structurally different types were
      tested in vitro for their antibacterial activity against 14 different bacterial
      species comprising a total of 187 strains. Ten compounds were able to inhibit
      growth of at least one strain at concentrations < or = 10 mumol/L. For three
      compounds, minimum inhibitory concentrations for some strains were even below 1
      mumol/L. Clear structure-activity relationships showed that the inhibitory effect
      depended on the bridge connecting the nitrogen atoms, the substitution of the
      nitrogens, and the number of nitrogen atoms present in one molecule.
      Substitutions like N-4-phenylbutyl, N-octyl, and N-nonyl were most active, while
      short (butyl) and long (dodecyl) substituents diminished or abolished the
      activity. The antimicrobial spectrum of the oligoamines tested here covered gram
      positive (e.g. Staphylococcus aureus, Listeria monocytogenes, Bacillus subtilis)
      and gram-negative (e.g. Escherichia coli, Citrobacter spp., Acinetobacter spp.)
      microorganisms. The type of action was classified as bactericidal. As the
      inhibition of growth is complete immediately after the addition of the
      oligoamines, an interaction with the bacterial cell-membrane is probable.

PMID- 9005816
TI  - New antifolate 4,4'-diaminodiphenyl sulfone substituted 2,4-diamino-5
      benzylpyrimidines. Proof of their dual mode of action and autosynergism.
AB  - New 4,4'-diaminodiphenylsulfone substituted 2,4-diamino-5-benzylpyrimidines were
      synthesized. These compounds are highly active inhibitors of both bacterial
      dihydrofolate reductase (DHFR) and dihydropteroic acid synthase (SYN). The
      simultaneous inhibition of both enzymes leads to autosynergism in whole cells in
      the same way as known for combinations of sulfonamides with trimethoprim. The
      inhibitory activity is demonstrated in cell-free systems of DHFR and SYN derived
      from various species (M. lufu, E. coli, C. albicans) and in whole cell systems of
      the mycobacterial strain M. lufu. The compounds are rare examples for the
      combination of two mechanisms of action in one molecule.

PMID- 9005817
TI  - [Immunophenotypic characterization of cutaneous neuroendocrine carcinoma derived
      from Merkel cells].
AB  - The following immunohistochemical markers were studied in 5 Merkel cell
      carcinomas: cytokeratins, epithelial membrane component, neuron-specific enolase,
      synaptophysin and chromogranin A. High expression of these markers in tumors
      allows one to consider them as having epithelial origin with neuroendocrine
      differentiation. Common leucocytic antigen proved to be very useful in
      differential diagnosis with malignant lymphoma.

PMID- 9005819
TI  - [Electron microscopic study of the nervous apparatus of the sinoatrial region of
      the human heart in alcoholic cardiomyopathy].
AB  - The EM study of the nerve components of the sinus node, adjacent contractile
      myocardium and nerve ganglions has been performed in 9 suddenly deceased males
      with alcoholic cardiomyopathy. A quantitative evaluation of the innervation
      density in the myocardium is given. Destructive changes were observed in the
      myelinized the non-myelinized nerve fibers of both conductive and contractile
      myocardium as well as in adjacent to the node nervous ganglions and their
      neurocytes and glia. Possible causes of the ultrastructural pathology in the
      sinoauricular region of the heart are discussed.

PMID- 9005818
TI  - [Urgent morphologic diagnosis of tracheal tumors in the course of roentgeno
      endoscopic study].
AB  - 84 tracheal tumors the correct diagnosis of which was established during
      roentgenoendoscopical investigation combined with urgent cytological diagnosis
      are reported. Cytological fast diagnosis can be considered a reliable method of
      morphological diagnostics.

PMID- 9005820
TI  - [Varying expression of atherosclerosis in the aortic regions with high and low
      density of the adrenergic nervous plexuses].
AB  - The study was made of early autopsies of 20-55-year-old victims deceased because
      of trauma. Incubation of sections in 2% glyoxylic acid and luminescent microscopy
      were used. The density of the adrenergic fibers in the central aortic zones which
      are most frequently affected with atherosclerosis was 2.8 +/- 0.2%, while in the
      distal rarely affected zones was 5.0 +/- 0.4%. In the abdominal aorta, the least
      density (2.1 +/- 2%) of the adrenergic plexuses was over the site of the celiac
      artery effluence, i.e. at the zones of the intensive atherosclerosis development
      while the density in the regions slightly affected with atherosclerosis it was
      3.8 +/- 0.3%. The results indicate possible permissive role of the sympathetic
      nervous system in the development of local atherosclerotic alterations.

PMID- 9005821
TI  - [Von Recklinghausen's disease: experimental models and comparative aspects].
AB  - Von Recklinghausen's disease, or neurofibromatosis type 1 (NF-1), is an autosomal
      dominant syndrome with a highly variable tumorous (neurofibromas, gliomas, Wilms'
      tumors, leukemia, pheochromocytomas) and non-tumorous (cafe-au-lait skin spots,
      iris and ciliar hamartomas, osseous lesions) manifestations. NF-1 gene is mapped
      to chromosome 17. Central or bilateral acoustic neurofibromatosis (NF-2) has a
      gene mapped to chromosome 22. Hereditary and sporadic NF-1 are recognized. The
      most typical manifestation of NF-1-skin neurofibroma--has has a characteristic
      plexiform structure. Spectrum of tumors (schwannomas, gliomas, Wilms' tumors)
      produced by transplacental treatment with strong environmental mutagens
      carcinogens-ethylnitroso- and methylnitrosourea (ENU and MNU, respectively)
      resembles on the whole that observed in human sporadic NF-1. Location of
      neurofibromas depends on the species: skin and subcutaneous tissue in humans,
      cattle and hamsters, trigeminal nerve, spinal roots in rats. Rat schwannomas
      differ from human neurofibromas by malignant structure, frequently with cystic
      component, but if induced by ENU treatment at day 15 of the pregnancy they
      resemble human plexiform neurofibromas with intraneural and extraneural growth of
      tumor cells. There were attempts to reproduce a transgenerational transmission of
      ENU carcinogenic effect, i.e. hereditary form of NF-1. In the experiments of this
      type the offsprings of rats prenatally treated with ENU remained untreated. The
      incidence of PNS, CNS and Wilms' tumors in these untreated offsprings in some
      experiments was significantly higher than in controls thus confirming the
      possibility, in principle, of hereditary NF-1 modelling. Only 10% of tumors
      developing in such untreated descendants of ENU treated parents contained a
      specific mutation of neu oncogene compared to 90-100% in tumors arising following
      direct treatment with ENU. The mechanisms of the transgenerational carcinogenesis
      are discussed. Lesions imitating NF-1 and in part NF-2 in transgenic mice with an
      HTLV-1-tax gene as well as in p-53 knockout mice are mentioned.

PMID- 9005822
TI  - [Mediacalcinosis of the aorta (pathomorphology and pathogenesis of arterial
      calcification and its relationship to atherosclerosis)].
AB  - It is established on the material of 116 legal-medical autopsies of 11-50-year
      old subjects deceased of occasional causes that calcinosis of the aorta media
      appears in subjects under 20 years and progresses with age. As distinct from the
      aorta, the first calcium deposits in the coronary arteries appear in the intima,
      in the foci of muscular-elastic hyperplasia. Calcium deposits in the coronary and
      other arteries appear a decade later than in the aorta. The beginning of the
      mediacalcinosis coincides in time with focal intima lipoidosis but the
      correlation between the intima thickening and the intensity of mediacalcinosis is
      not observed. Calcinosis of the atherosclerotic plaques appears in preexisting
      mediacalcinosis. Calcium deposits are closely linked with the elastica, and the
      media calcinosis occurs in the elastica destruction and is not followed by
      proliferation of the smooth cells. Cell membrane fragments and vesicular
      structures are found ultrastructurally in the calcinosis foci, this suggesting
      that the mediacalcinosis is connected with the elastica destruction and the
      smooth cell death.

PMID- 9005823
TI  - [Atherosclerosis in diabetes mellitus (repeated epidemiologic studies of
      atherosclerosis with an interval of 25 years)].
AB  - Repeated epidemiological studies of atherosclerosis were performed in 1985-1989
      (as compared to 1965-1968) in 20-59-year-old males of malme, praha, Tallinn,
      Yalta and in 40-59-year-old females in Malme, Riga and Yalta. 358 cases of
      diabetes mellitus (DM) were studied. DM occurred more frequently during the
      second interval as compared to the first one: 6.3 and 4.6% in males, and 7.6 and
      4.2% in females, respectively. The severity of atherosclerosis (aorta and
      coronary arteries were studied morphometrically after staining with Sudan IV) was
      higher in patients with DM the influence of which was similar to that of the
      arterial hypertension. The severity of atherosclerosis in DM depended, to a
      certain degree, on atherosclerosis level in the population. There was a trend to
      a decrease of atherosclerosis severity within the second interval in Malme and
      Praha, and its increase in Riga, Tallinn and Yalta. There was no significant
      difference in atherosclerosis severity that would depend on DM severity and
      regularity of its treatment.

PMID- 9005824
TI  - [Morphologic and functional changers in B-cells and vessels of the islands of
      Langerhans in patients with insulin-dependent diabetes mellitus].
AB  - Pancreatic biopsies from 49 patients with IDDM were studied. Ultrastructurally, a
      heterogeneity of B-cell morphological changes and microangiopathy of the
      Langerhans islands were observed. Langerhans islands containing B-cells with
      destructive changes were found in 27 biopsies, sclerosis and hyalinosis of
      vascular wall in 6 biopsies. Langerhans islands sclerosis was found in 13
      biopsies and in 9 biopsies, in normal structure of the acinar compartment of the
      pancreas, Langerhans islands were not found. The authors findings and literature
      data allowed the conclusion on the stage pattern of IDDM development. The basis
      is an immune, autoimmune mechanism of B-cell and endotheliocyte of the Langerhans
      islands damage, and therefore, a decrease of the (pro)insulin synthesis and its
      transport into the circulation. This process is genetically predetermined, this
      being confirmed by the lack of the dependence of B-cell and vessels damage in the
      Langerhans islands upon the age and small fluctuations in the manifestations and
      duration of the disease.

PMID- 9005825
TI  - [Comparative morphologic characteristics of viral hepatitis B and C].
AB  - Using liver biopsies in chronic HBV and HCV infections and their combination, the
      authors found between them morphological difference represented by nonspecific
      morphological markers. The combination of fat and hydropic hepatocytes
      degeneration, their heterogeneity, lymphoid follicles of various location and
      maturation degree, sinusoidal cell hyperplasia, accumulation of lymphocytes and
      macrophages in sinusoids, destruction, proliferation and sclerosis of ductules
      are of a high significance in hepatitis C. Etiological markers of hepatitis B are
      so-called ground-glass hepatocytes and "sand" nuclei. Various combination of
      these markers are characteristic for HBV and HCV co-infections with predominance
      among them of a replicating virus.

PMID- 9005826
TI  - [Pathohistologic and ultrastructural features of drug-induced membranous
      glomerulonephritis].
AB  - Nephrobiopsies of 20 patients with drug-induced membranous glomerulonephritis
      were studied. Renal injury was produced by diuretics (7 patients), gold salts
      (6), penicillamine (4), captopril (3). Drug-induced membranous glomerulonephritis
      in contrast to idiopathic one ran a benign course after proper therapy based on
      discontinuation of the drug. Main pathomorphological features of secondary
      membranous glomerulonephritis that help to differentiate it from the primary one
      were established: absence of total injury of the glomeruli, hypercellularity of
      the damaged glomeruli, pathomorphological changes only of the part of the
      capillary loops, presence of both subepithelial and mesangial deposits.

PMID- 9005827
TI  - [Combined pathology of the pancreas and myocardium in myocardial infarction and
      acute destructive pancreatitis].
AB  - Pancreas was studied in 30 patients who died of myocardial infarction (MI). Total
      pancreonecrosis was found in 1 case (recurring MI), diffuse focal pancreonecrosis
      in 3 cases (the second MI). Local microcirculation disturbances, thrombosis of
      some interlobular veins, degenerative changes of the exocrine pancreocytes with
      translocation of zymogen granules and their parapedesis into the edematous
      interstitium were found in all other cases. Focal metabolic myocardial damage and
      circulation disturbances mainly in the subendocardium of the left ventricle
      myocardium were found in the heart of 3 patients who died of pancreonecrosis and
      60 white rats with pancreatitis induced by chloroethyl. There was a
      redistribution of Ca2+ in the ultrastructural components of the cardiomyocytes
      with its accumulation in the cytosol and sarcoplasmic reticulum. The most
      pronounced and widespread myocardial damage was observed in the hemorrhagic stage
      of pancreatitis.

PMID- 9005828
TI  - [Frequency and morphology of DIC-syndrome in children in early neonatal period].
AB  - Morphological study of 120 autopsy cases of newborns who died of intrauterine
      pneumonia, respiratory distress, hemorrhage into the brain ventricles and
      asphyxia revealed that in all these diseases intravascular blood coagulation
      develops which can be disseminated or local. Morphological manifestations of DIC
      syndrome in newborns are described. The development of DIC-syndrome 18-24 hours
      before death is considered as a sign of compensatory-adaptive failure at the
      level of microcirculatory bed (type of "blood degeneration").

PMID- 9005829
TI  - [Morphologic characteristics of epidermal cells in HIV infection].
AB  - Skin biopsies at the plaque regions and adjacent skin obtained from HIV-infected
      22-40-year-old patients with Kaposi's sarcoma have been analyzed. Morphological
      changes revealed depended on the stage of the disease and cell specificity. The
      alterations were as follows: cell adenoma with degeneration and destruction of
      cell organelles, changes of the specific granules and microfilaments. Langerhans
      cells appeared to be most susceptible to HIV and showed all types of changes. In
      the course of the disease gradual decrease of the activity of the main metabolic
      enzyme - adenylate cyclase - was recorded.

PMID- 9005830
TI  - [An attempt to adopt computer technology in the pathology bureau].
AB  - The experience of computer facilities introduction in Taganrog regional pathology
      bureau (TRPB) is presented. A special program "Autopsy" for pathologists
      developed by TRPB specialists is described. The hardware and the structure of
      TRPB local computer network is described. Application of the program in the
      activities of the bureau is detailed. The results of the program trial in 1995
      and prospects of the program introduction in the activities of pathology service
      of the Rostov region are outlined.

PMID- 9005832
TI  - [Apoptosis].
AB  - Apoptosis is a special form of cell death morphologically characterized by a
      pronounced cell shrinkage with subsequent fragmentation into the apoptotic bodies
      surrounded by a membrane and phagocyted by macrophages without inflammatory
      reaction. Apoptosis (a programmed or physiological cell death) plays an important
      role in embryo-genesis, organ involution, ageing, but may arise in pathology when
      genetic apparatus of the cell is damaged: radiation, viral infection,
      carcinogenesis. The level of apoptosis predetermines tumor progression, onset and
      course of viral diseases. Apoptosis maintains constant cell number in the organs
      and removes cells either damaged or finished their life cycle. Classification of
      the apoptosis assense may promote the solution of the problem of life span
      prolongation.

PMID- 9005833
TI  - [Morphologic and morphogenetic features of stomach ulcer].
AB  - Literature data are reviewed concerning morphological and morphogenetic features
      of stomach ulcer, vascular alterations in both the ulcer zone and other regions
      of the stomach. Stages in ulcer formation, its healing and prognostic criteria
      are described. Further study of ulcerogenesis regarding histotopographic features
      of different regions of gastro-intestinal tract is recommended.

PMID- 9005831
TI  - [Analysis of morphometric parameters of utero-placental metabolism].
AB  - Several stages in the study of utero-placental metabolism are described. First is
      measuring of the placenta volume, its fixation, then follows determination of the
      stereomicroscopic characteristics of the placenta. The third stage is
      measurements of resorptive placenta surface, and the fourth-estimation of
      morphometric values of the utero-placental metabolism. Integral values of this
      metabolism and the amount of blood per resorptive surface unit is recommended to
      determine allowing for morphology of the villi. All the morphometric values are
      expressed in the absolute units in relation to the total placenta volume.

PMID- 9005834
TI  - [Quantification of feline immunodeficiency virus (FIV) RNA in the plasma of
      infected cats].
AB  - A competitive reverse transcription-polymerase chain reaction (RT-PCR) was used
      to quantify RNA of feline immunodeficiency virus (FIV) in cats. The assay uses in
      vitro synthesized RNA as a competitive internal control. The synthesized RNA has
      a 22-base deletion with respect to the wild-type sequence. PCR products were
      quantitated by densitometric analysis of a digitized image of the ethidium
      bromide stained gel. Viral RNA concentrations in the plasma of two cats
      experimentally infected with FIV strain UT113 were followed for 32 weeks; peak
      copy numbers (2.3 x 10(4) and 1.3 x 10(4) per ml, respectively) were reached 11
      weeks after subcutaneous injection of ten 50% cat infectious doses. With rising
      antibody titers against FIV-gag and FIV-env gene products, the amount of FIV RNA
      in plasma decreased. Nine asymptomatic cats that had been experimentally infected
      3.5 to 4.5 years earlier had copy numbers between 5.6 x 10(3) and 4.3 x 10(4) per
      ml. Cats treated for six weeks with 9-(2-phosphonylmethoxy-propyl)-2,6
      diaminopurine [PMPDAP] (20 mg/kg body weight s.c. three times a week) showed a
      significant decrease of RNA copy numbers in plasma. This quantitative competitive
      RT-PCR will be useful to study the pathogenesis of the FIV infection, to evaluate
      the effectiveness of vaccines and to monitor antiviral and immunomodulating
      drugs.

PMID- 9005835
TI  - [A method for specific isolation of verotoxin-producing Escherichia coli
      colonies].
AB  - The described colony immunoblot is a special double membrane-agar technology,
      which permits the specific isolation of VTEC in biological materials decided VT
      positive by EIA or PCR. The produced Verotoxin (VT) is detected on the surface of
      the lower membrane by help of monoclonal antibodies. A direct allocation of the
      corresponding VT-expressing E. coli-colonies on the upper membrane is possible.
      So the isolation and further characterisation of potential VTEC is practicable in
      materials with a high microbial contamination too. This isolation method is
      available for the examination of VT-positive faeces and foods. In the case of
      foods it is necessary to work with an enrichment culture.

PMID- 9005836
TI  - [Antibody titers against Borrelia in horses in serum and in eyes and occurrence
      of equine recurrent uveitis].
AB  - In Germany very little is known about antibody titers against Borrelia
      burgdorferi in the horse. In the USA there exist some studies on the titer levels
      and symptoms due to borrelia infections. Beside lameness, fever, polyarthritis,
      pneumonia and dullness there is a study showing a connection between panuveitis
      and Borrelia infection in the horse. In human medicine the infection with
      Borrelia burgdorferi becomes more and more important. Uveitis and other eye
      diseases due to Borrelia burgdorferi are proved and documented. The goal of this
      study was to find a connection between antibodies to Borrelia burgdorferi and
      cases of equine recurrent uveitis (ERU). The antibody titer against Borrelia
      burgdorferi was determined by IFT in 153 horses with no sign of disease of the
      eye and in 79 horses with equine recurrent uveitis (ERU). 48% of all horses were
      found to be positive (titer 1:64 or higher). In addition 22 sera were tested in
      western-blot for antibody titers. There was no significant correlation between
      signs of ERU and increased antibody titers against Borrelia burgdorferi (p >
      0.05). No clinical signs were seen in horses with elevated titers. No correlation
      between the age of the horses and the antibody level could be found. There was a
      connection between the antibody titer and the month of examination (p < 0.05).
      Highest titer levels were seen in May and November. This is both one month later
      than the activity of the transmitting ticks (I. ricinus).

PMID- 9005837
TI  - [Hemophilia A in the dog: symptoms, blood coagulation analysis and treatment].
AB  - In our patients, haemophilia A was observed in German shepherd dogs and Siberian
      huskies. Frequently occurring clinical symptoms were excessive bleeding from the
      gums, when getting adult teeth, and haematomas in the regions of the proximal
      hindleg, the knee joint as well as the chest or abdominal wall, respectively. The
      activated partial thromboplastin time (aPTT) as a screening test of the intrinsic
      coagulation system reflects sensitively also a mildly reduced factor VIII:C
      activity which may be present for example during substitution therapy. Therefore,
      the aPTT is well suited for screening for haemophilia A. In haemophilic dogs
      suffering from hypovolaemic shock due to a considerable acute blood loss, besides
      the aPTT also the prothrombin time and partly the platelet number were beyond the
      respective reference range due to loss and consumption of coagulation factors and
      thrombocytes. For substitution therapy, fresh frozen plasma was used in the first
      line. Administered at a dose of 15 or 20 ml/kg BW, it caused an increase of
      factor VIII:C activity by 20 or 33%, respectively. 24 hours after the end of
      infusion the mean of the remaining activity increase in comparison with the value
      measured immediately after substitution was 27%. The fast, biphasic elimination
      of factor VIII:C in some cases required a repeated application until clinical
      recovery. Desmopressin acetate given at a dose of 1 microgram/kg KGW
      intravenously or subcutaneously to two dogs each did not cause a distinct
      increase of the factor VIII:C activity, and is, therefore, not an efficacious
      supplementary therapy to substitution therapy in haemophilic dogs.

PMID- 9005838
TI  - [Endoscopy of body cavities and minimally invasive surgery in small animals-
      review].
AB  - A report is given on principles and possibilities of diagnostic laparoscopy,
      thoracoscopy, cystoscopy and arthroscopy in dogs. Ovariectomy, ovarihysterectomy
      and castration of cryptorchid dogs are mentioned as examples for possible minimal
      invasive surgery.

PMID- 9005839
TI  - [Life expectancy and cause of death in dogs. I. The situation in mixed breeds and
      various dog breeds].
AB  - The present study on life expectancy and cause of death is based upon data from
      9,248 dogs. The entire sample showed a life expectancy of 10.0 years. The most
      frequent cause of death was tumors (27.3%), followed by cardiac and circulatory
      ailments (16.3%). The causes of death also showed a breed-specific distribution.
      The mean age attained in various breeds differed, ranging from 6.8 years in the
      Berner Sennenhund to 13.0 years in the Pudel. Dogs of mixed breeding tended not
      to differ from purebreds either in their life expectancy or in their cause of
      death.

PMID- 9005840
TI  - [The optimization of group size for fattening rabbits in group housing on grids
      made of artificial material].
AB  - ZIKA-fattening rabbits in groups of 4, 8, 16, 32 and 64 animals (5 rabbits/m2)
      have been proved in 6 repetitions with all together 144 animals during the
      fattening period of nine weeks in regard to their fattening performance, health
      and behaviour. The aim was to find an optimal group size for fattening rabbits
      with respect to animal welfare. The results show, that fattening performance and
      health of the rabbits have not been influenced remarkably by group size, whereas
      behaviour was different in so far, as the rabbits in groups of 16 showed a
      greater percentage of relaxed positions as well as a remarkable smaller
      percentage of aggressive behaviour. Therefore the group with 16 fattening rabbits
      is that, which can be advised for the fattening of rabbits in the Hohenheimer
      group housing.

PMID- 9005841
TI  - Biosynthesis and function of all-trans- and 9-cis-retinoic acid in parathyroid
      cells.
AB  - We demonstrate that cultured human and bovine parathyroid cells incubated with
      all-trans-[11,12-3H]-retinol convert this tracer into all-trans- and 9-cis
      retinoic acid. By using RT-PCR, cellular retinol-binding protein type I (CRBP I),
      cellular retinoic acid binding protein I and II (CRABP I and II), retinoic acid
      receptors (RARs) alpha, beta and gamma, and 9-cis-retinoic acid receptor (RXR)
      alpha transcripts were detected in human parathyroid cDNA. CRBP I and CRABP I
      expression was confirmed by immunohistochemistry. Both 9-cis- and all-trans-RA
      were found to suppress parathyroid hormone (PTH) secretion from dispersed human
      adenomatous parathyroid cells, which was augmented by combined treatment with 1mM
      RA and 100 nM 1,25 (OH)2D3. The present data establish parathyroid gland as a
      target for retinoids and as a site of synthesis of the hormonal forms of vitamin
      A (retinol), all-trans- and 9-cis-retinoic acid.

PMID- 9005842
TI  - How cells get the right chromosomes.
AB  - When cells divide, the chromosomes must be delivered flawlessly to the daughter
      cells. Missing or extra chromosomes can result in birth defects and cancer.
      Chance events are the starting point for chromosome delivery, which makes the
      process prone to error. Errors are avoided by diverse uses of mechanical tension
      from mitotic forces. Tension stabilizes the proper chromosome configuration,
      controls a cell cycle checkpoint, and changes chromosome chemistry.

PMID- 9005843
TI  - Observation of Interference Between Two Bose Condensates
AB  - Interference between two freely expanding Bose-Einstein condensates has been
      observed. Two condensates separated by approximately 40 micrometers were created
      by evaporatively cooling sodium atoms in a double-well potential formed by
      magnetic and optical forces. High-contrast matter-wave interference fringes with
      a period of approximately 15 micrometers were observed after switching off the
      potential and letting the condensates expand for 40 milliseconds and overlap.
      This demonstrates that Bose condensed atoms are "laser-like"; that is, they are
      coherent and show long-range correlations. These results have direct implications
      for the atom laser and the Josephson effect for atoms.

PMID- 9005844
TI  - Photochemically driven collapse of Titan's atmosphere.
AB  - Saturn's giant moon Titan has a thick (1.5 bar) nitrogen atmosphere, which has a
      temperature structure that is controlled by the absorption of solar and thermal
      radiation by methane, hydrogen, and organic aerosols into which methane is
      irreversibly converted by photolysis. Previous studies of Titan's climate
      evolution have been done with the assumption that the methane abundance was
      maintained against photolytic depletion throughout Titan's history, either by
      continuous supply from the interior or by buffering by a surface or near surface
      reservoir. Radiative-convective and radiative-saturated equilibrium models of
      Titan's atmosphere show that methane depletion may have allowed Titan's
      atmosphere to cool so that nitrogen, its main constituent, condenses onto the
      surface, collapsing Titan into a Triton-like frozen state with a thin atmosphere.

PMID- 9005845
TI  - Earth-Based Radio Tracking of the Galileo Probe for Jupiter Wind Estimation
AB  - Although the Galileo probe was designed to communicate only to the orbiter, the
      probe radio signal was detected at two Earth-based radio observatories where the
      signal was a billion times weaker. The measured signal frequency was used to
      derive a vertical profile of the jovian zonal wind speed. Due to the mission
      geometry, the Earth-based wind estimates are less sensitive to descent trajectory
      errors than estimates based on probe-orbiter Doppler measurements. The two
      estimates of wind profiles agree qualitatively; both show high wind speeds at all
      depths sampled.

PMID- 9005846
TI  - Microscopic Growth Mechanisms for Carbon Nanotubes
AB  - The uncatalyzed edge growth of carbon nanotubes was investigated by first
      principles molecular dynamics simulations. At experimental temperatures the open
      end of single-walled nanotubes closed spontaneously into a graphitic dome, which
      may explain why these nanotubes do not grow in the absence of transition metal
      catalysts. On the other hand, chemical bonding between the edges of adjacent
      coaxial tubes ("lip-lip" interactions) trapped the end of a double-walled
      nanotube in a metastable energy minimum, thus preventing dome closure. These
      calculations show that this end geometry exhibits a high degree of chemical
      activity and easily accommodates incoming carbon fragments, supporting a model of
      growth by chemisorption from the vapor phase.

PMID- 9005847
TI  - A Silicon Single-Electron Transistor Memory Operating at Room Temperature
AB  - A single-electron memory, in which a bit of information is stored by one
      electron, is demonstrated at room temperature. The memory is a floating gate
      metal-oxide-semiconductor transistor in silicon with a channel width (
      approximately 10 nanometers) smaller than the Debye screening length of a single
      electron and a nanoscale polysilicon dot ( approximately 7 nanometers by 7
      nanometers) as the floating gate embedded between the channel and the control
      gate. Storing one electron on the floating gate screens the entire channel from
      the potential on the control gate and leads to (i) a discrete shift in the
      threshold voltage, (ii) a staircase relation between the charging voltage and the
      shift, and (iii) a self-limiting charging process. The structure and fabrication
      of the memory should be compatible with future ultralarge-scale integrated
      circuits.

PMID- 9005848
TI  - Micropatterning fluid lipid bilayers on solid supports.
AB  - Lithographically patterned grids of photoresist, aluminum oxide, or gold on
      oxidized silicon substrates were used to partition supported lipid bilayers into
      micrometer-scale arrays of isolated fluid membrane corrals. Fluorescently labeled
      lipids were observed to diffuse freely within each membrane corral but were
      confined by the micropatterned barriers. The concentrations of fluorescent probe
      molecules in individual corrals were altered by selective photobleaching to
      create arrays of fluid membrane patches with differing compositions. Application
      of an electric field parallel to the surface induced steady-state concentration
      gradients of charged membrane components in the corrals. In addition to producing
      patches of membrane with continuously varying composition, these gradients
      provide an intrinsically parallel means of acquiring information about molecular
      properties such as the diffusion coefficient in individual corrals.

PMID- 9005849
TI  - Magnetic Collapse in Transition Metal Oxides at High Pressure: Implications for
      the Earth
AB  - Magnetic collapse in transition metal ions is predicted from first-principles
      computations at pressures reached in the Earth's lower mantle and core. Magnetic
      collapse would lead to marked changes in geophysically important properties, such
      as elasticity and conductivity, and also to different geochemical behavior, such
      as element partitioning, than estimated by extrapolating low-pressure data, and
      thus change the understanding of Earth's structure and evolution. Magnetic
      collapse results from band widening rather than from changes in crystal field
      splitting under pressure. Seismic anomalies in the outer core and the lowermost
      mantle may be due to magnetic collapse of ferrous iron, dissolved in iron liquid
      in the outer core, and in solution in magnesiowustite in the lowermost mantle.

PMID- 9005850
TI  - A general strategy for selecting high-affinity zinc finger proteins for diverse
      DNA target sites.
AB  - A method is described for selecting DNA-binding proteins that recognize desired
      sequences. The protocol involves gradually extending a new zinc finger protein
      across the desired 9- or 10-base pair target site, adding and optimizing one
      finger at a time. This procedure was tested with a TATA box, a p53 binding site,
      and a nuclear receptor element, and proteins were obtained that bind with
      nanomolar dissociation constants and discriminate effectively (greater than
      20,000-fold) against nonspecific DNA. This strategy may provide important
      information about protein-DNA recognition as well as powerful tools for
      biomedical research.

PMID- 9005851
TI  - Regulation of neuronal survival by the serine-threonine protein kinase Akt.
AB  - A signaling pathway was delineated by which insulin-like growth factor 1 (IGF-1)
      promotes the survival of cerebellar neurons. IGF-1 activation of phosphoinositide
      3-kinase (PI3-K) triggered the activation of two protein kinases, the serine
      threonine kinase Akt and the p70 ribosomal protein S6 kinase (p70(S6K)).
      Experiments with pharmacological inhibitors, as well as expression of wild-type
      and dominant-inhibitory forms of Akt, demonstrated that Akt but not p70(S6K)
      mediates PI3-K-dependent survival. These findings suggest that in the developing
      nervous system, Akt is a critical mediator of growth factor-induced neuronal
      survival.

PMID- 9005852
TI  - Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4
      bisphosphate.
AB  - The regulation of the serine-threonine kinase Akt by lipid products of
      phosphoinositide 3-kinase (PI 3-kinase) was investigated. Akt activity was found
      to correlate with the amount of phosphatidylinositol-3,4-bisphosphate (PtdIns-3,4
      P2) in vivo, and synthetic PtdIns-3,4-P2 activated Akt both in vitro and in vivo.
      Binding of PtdIns-3,4-P2 occurred within the Akt pleckstrin homology (PH) domain
      and facilitated dimerization of Akt. Akt mutated in the PH domain was not
      activated by PI 3-kinase in vivo or by PtdIns-3, 4-P2 in vitro, and it was
      impaired in binding to PtdIns-3,4-P2. Examination of the binding to other
      phosphoinositides revealed that they bound to the Akt PH domain with much lower
      affinity than did PtdIns-3,4-P2 and failed to increase Akt activity. Thus, Akt is
      apparently regulated by the direct interaction of PtdIns-3,4-P2 with the Akt PH
      domain.

PMID- 9005854
TI  - Preattentive filling-in of visual surfaces in parietal extinction.
AB  - Unilateral brain damage frequently produces "extinction," in which patients can
      detect brief single visual stimuli on either side but are unaware of a
      contralesional stimulus if presented concurrently with an ipsilesional stimulus.
      Explanations for extinction have invoked deficits in initial processes that
      operate before the focusing of visual attention or in later attentive stages of
      vision. Preattentive vision was preserved in a parietally damaged patient, whose
      extinction was less severe when bilateral stimuli formed a common surface, even
      if this required visual filling-in to yield illusory Kanizsa figures or
      completion of partially occluded figures. These results show that parietal
      extinction arises only after substantial processing has generated visual
      surfaces, supporting recent claims that visual attention is surface-based.

PMID- 9005853
TI  - Identification of a gene that causes primary open angle glaucoma.
AB  - Glaucoma is a major cause of blindness and is characterized by progressive
      degeneration of the optic nerve and is usually associated with elevated
      intraocular pressure. Analyses of sequence tagged site (STS) content and
      haplotype sharing between families affected with chromosome 1q-linked open angle
      glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening.
      A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest
      disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma
      patients were found to have one of three mutations in this gene (3.9 percent of
      the population studied). One of these mutations was also found in a control
      individual (0.2 percent). Identification of these mutations will aid in early
      diagnosis, which is essential for optimal application of existing therapies.

PMID- 9005855
TI  - NMDA channel regulation by channel-associated protein tyrosine kinase Src.
AB  - The N-methyl-D-aspartate (NMDA) receptor mediates synaptic transmission and
      plasticity in the central nervous system (CNS) and is regulated by tyrosine
      phosphorylation. In membrane patches excised from mammalian central neurons, the
      endogenous tyrosine kinase Src was shown to regulate the activity of NMDA
      channels. The action of Src required a sequence [Src(40-58)] within the
      noncatalytic, unique domain of Src. In addition, Src coprecipitated with NMDA
      receptor proteins. Finally, endogenous Src regulated the function of NMDA
      receptors at synapses. Thus, NMDA receptor regulation by Src may be important in
      development, plasticity, and pathology in the CNS.

PMID- 9005857
TI  - Comparative rates of development in Monodelphis and Didelphis.

PMID- 9005856
TI  - Positive selection of T cells induced by viral delivery of neopeptides to the
      thymus.
AB  - The relation between an antigenic peptide that can stimulate a mature T cell and
      the natural peptide that promoted selection of this cell in the thymus is still
      unknown. An experimental system was devised to address this issue in vivo-mice
      expressing neopeptides in thymic stromal cells after adenovirus-mediated delivery
      of invariant chain-peptide fusion proteins. In this system, selection of T cells
      capable of responding to a given antigenic peptide could be promoted by the
      peptide itself, by closely related analogs lacking agonist and antagonist
      activity, or by ostensibly unrelated peptides. However, the precise repertoire of
      T cells selected was dictated by the particular neopeptide expressed.

PMID- 9005858
TI  - Recent advances in heritable ataxias.

PMID- 9005859
TI  - The pathology of Alzheimer's disease: numbers count.

PMID- 9005860
TI  - Familial episodic ataxia: clinical heterogeneity in four families linked to
      chromosome 19p.
AB  - We describe the clinical and oculographic findings in 4 families with episodic
      ataxia and interictal nystagmus (EA-2) linked to chromosome 19p. Episodes varied
      from pure ataxia to combinations of symptoms suggesting involvement of the
      cerebellum, brainstem, and cortex. Some affected individuals exhibited a
      progressive ataxia syndrome phenotypically indistinguishable from the dominantly
      inherited spinocerebellar ataxia (SCA) syndromes. About one-half of the affected
      individuals had migraine headaches and several had episodes typical of basilar
      migraine. Oculographic findings were localizing to the vestibulocerebellum and
      posterior vermis. Additional genetic and environmental factors must account for
      the marked clinical heterogeneity in these families with an abnormal gene on
      chromosome 19p.

PMID- 9005861
TI  - Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's
      disease.
AB  - To assess the relationship between dementia, neuronal loss, and neuropathological
      findings in Alzheimer's disease (AD), we counted the number of neurons, senile
      plaques, and neurofibrillary tangles in a high-order association cortex. We
      studied the superior temporal sulcus of 34 individuals with AD and 17 nondemented
      control subjects, using statistically unbiased, stereological counting
      techniques. The number of superior temporal sulcus neurons in nondemented control
      subjects was stable across the sixth to ninth decades. In AD, more than 50% of
      the neurons were lost. Both neuronal loss and neurofibrillary tangles increased
      in parallel with the duration and severity of illness, but the amount of neuronal
      loss exceeded by manyfold the amount of neurofibrillary tangles accumulated. In
      contrast to the correlation between neurofibrillary tangles and neuronal loss,
      the number of senile plaques and the percentage of the superior temporal sulcus
      that was covered by Abeta (amyloid burden) were not related to neuronal loss,
      number of neurofibrillary tangles, or duration of disease. Neither the amount nor
      the rate of neuronal loss in the superior temporal sulcus in AD correlated with
      apolipoprotein E genotype. These data suggest that neuronal loss in association
      areas such as the superior temporal sulcus contributes directly to cognitive
      impairment in AD.

PMID- 9005862
TI  - A rapidly progressive adolescent-onset oculopharyngeal somatic syndrome with
      rimmed vacuoles in two siblings.
AB  - We describe 2 Greek siblings who developed a rapidly progressive oculopharyngeal
      somatic syndrome, at the ages of 11 and 14 years, with muscle biopsies showing
      rimmed vacuoles and, in 1 case, cytoplasmic and intranuclear tubulofilamentous
      inclusions 25 nm in diameter. Although a similar pattern of muscle involvement
      with rimmed vacuoles is described in autosomal dominant oculopharyngeal muscular
      dystrophy, the age of onset, the rapid progression of the symptoms, and the
      nature of the tubulofilaments distinguish this as a separate entity.

PMID- 9005863
TI  - Activation mapping in essential tremor with functional magnetic resonance
      imaging.
AB  - We used functional magnetic resonance imaging (FMRI) to study possible cerebral
      activation patterns associated with unilateral postural tremor in 12 patients
      with essential tremor (ET), with mimicked postural tremor in 15 control subjects,
      and with passive wrist oscillation in both groups. During essential tremor,
      patients showed mainly contralateral activation of the primary motor and primary
      sensory areas, the globus pallidus, and the thalamus, but bilateral activation of
      the nucleus dentatus, the cerebellar hemispheres, and the red nucleus. Only 2
      patients presented with activity in the medulla close to the olivary nucleus.
      Unilateral passive wrist oscillation of ET patients resulted in only unilateral
      activation of the cerebellum, nuclei dentati, and red nuclei. In contrast to the
      involuntary tremor condition of ET patients, the mimicked tremor condition of the
      control subjects was not associated with bilateral activity in the cerebellum,
      nuclei dentati, or red nuclei. Involuntary tremor of ET patients was associated
      with a significantly larger extent of activation in the cerebellar hemispheres
      and the red nucleus (p < 0.003) compared with mimicked tremor in the control
      group. Our FMRI study indicates that ET is mainly associated with an additional
      contralateral cerebellar pathway activation and overactivity in the cerebellum,
      red nucleus, and globus pallidus without significant intrinsic olivary
      activation.

PMID- 9005864
TI  - The spectrum of hippocampal sclerosis: a quantitative magnetic resonance imaging
      study.
AB  - One hundred patients with intractable temporal lobe epilepsy and 22 control
      subjects were scanned on a 1.5-T Siemens SP63 Magnetom scanner. A combination of
      hippocampal T2 mapping, hippocampal volume measurement corrected for intracranial
      volume, and inspection of hippocampal morphology on a hippocampal volume
      distribution graph compared with a control graph revealed previously undetected
      forms of bilateral hippocampal sclerosis and four false-positive diagnoses of
      hippocampal sclerosis made on visual inspection of the scans. A physiological
      asymmetry in the position of the hippocampi in 41% of control subjects and focal
      hippocampal atrophies in patients made measurement of the whole length of the
      hippocampus mandatory. The extent of hippocampal damage in patients with
      hippocampal sclerosis correlated with the number of secondary generalized
      seizures during a patient's lifetime. In contrast to patients with unilateral
      hippocampal sclerosis, patients with severe bilateral hippocampal sclerosis had
      no history of febrile convulsions. Twenty-six patients with intractable temporal
      lobe epilepsy had normal hippocampal magnetic resonance imaging measures and as a
      group were significantly older at the onset of habitual epilepsy than were
      patients with hippocampal sclerosis. In conclusion, a combination of quantitative
      magnetic resonance imaging techniques revealed a spectrum of hippocampal
      sclerosis and optimally defined boundaries of hippocampal normality. The spectrum
      of hippocampal sclerosis is related to the etiology, the number of secondary
      generalized seizures, and the age at onset of habitual epilepsy.

PMID- 9005865
TI  - Amyloid (Abeta) deposition in chromosome 1-linked Alzheimer's disease: the Volga
      German families.
AB  - Amyloid beta protein (Abeta) deposition was investigated in the frontal cortex of
      6 cases of (genetically confirmed) chromosome 1-linked Alzheimer's disease (AD)
      (PS-2 gene mutation) among the Volga German families using the end-specific
      monoclonal antibodies BA27 and BC05 to detect the presence of Abeta40 and
      Abeta42(43), respectively. In all patients, Abeta42(43) was the predominant
      peptide species present, although the total amount of Abeta40 and Abeta42(43)
      deposited in plaques did not differ from that seen in sporadic AD and was
      significantly lower than that occurring in AD due to PS-1 gene mutations.
      Therefore, mutations in the PS-2 gene, like those in the presenilin-1 (PS-1) and
      amyloid precursor protein (APP) genes, are associated with an initial and
      preferential deposition of Abeta42(43) within the brain. Although the
      mechanism(s) whereby the PS-1 and PS-2 gene mutations operate remains unclear, it
      seems from the present study that the effect of the PS-2 gene mutation on the
      brain is much less severe, at least as far as Abeta deposition is concerned, than
      that of the PS-1 mutation, which seems to confer a much earlier and a much more
      aggressive development of AD.

PMID- 9005866
TI  - Which clinical sign of Parkinson's disease best reflects the nigrostriatal
      lesion?
AB  - Clinical scales, based on the major signs of Parkinson's disease (PD), are
      commonly used to assess the effect of symptomatic treatment of PD. With the
      appearance of therapy aiming to rescue or protect the nigrostriatal neurons in
      PD, it becomes essential to define which of these signs best reflects the
      underlying neuronal deficit. Fluorodopa positron emission tomography has been
      shown to correlate with postmortem nigral cell counts. We correlated the major
      signs of PD with positron emission tomography results in 35 PD patients. We found
      that in the "practically defined off" state, (1) Purdue pegboard scores
      correlated best with the nigrostriatal dopaminergic deficit; (2) of the subscales
      of the modified Columbia score, the bradykinesia subscale correlated best; (3)
      rigidity and postural disturbance correlated less highly than bradykinesia, and
      their inclusion in a multiple regression did not improve the correlation of
      pegboard or bradykinesia scores alone; and (4) tremor did not correlate with the
      nigrostriatal dopaminergic deficit. We conclude that pegboard and bradykinesia
      scores represent the best clinical measures for studying the effect of treatment
      on the evolution of the nigrostriatal lesion of PD. Inclusion of other clinical
      signs provides additional information only for the study of functional
      impairments.

PMID- 9005867
TI  - Bilateral parasagittal parietooccipital polymicrogyria and epilepsy.
AB  - We describe 9 patients with a bilateral malformation of cortical development,
      centered around the parasagittal and mesial aspects of the parietooccipital
      cortex, with magnetic resonance imaging findings suggestive of polymicrogyria. No
      familial distribution or etiologic factors were identified. Location in a
      watershed area between anterior and posterior cerebral arteries suggests
      postmigratory perfusion failure as the underlying cause. In most patients the
      malformation was detected by magnetic resonance imaging after computed tomography
      scans with 10-mm-thick sections were considered normal. Seizures, present in all,
      had started between the ages of 20 months and 15 years (mean, 9 years) and were
      intractable in 7. Complex partial seizures with or without minor automatisms were
      the most frequent ictal pattern. In only 4 patients these were preceded by
      symptoms indicating posterior onset. Interictal electroencephalograms showed both
      diffuse and bilateral parietooccipital or temporal abnormalities. The range of IQ
      scores indicated average intelligence to mild retardation. Several patients
      presented deficits on neuropsychological tasks requiring performance under time
      constraints, suggesting that the malformation may result in cognitive slowing.
      Early diagnosis of this malformation may be difficult because of the lack of
      neurological signs, relatively late seizure onset, difficulty in localizing
      seizure onset, and inability to recognize the cortical abnormality on computed
      tomography scans.

PMID- 9005868
TI  - Proton magnetic resonance spectroscopic imaging for discrimination of absence and
      complex partial seizures.
AB  - We performed proton magnetic resonance spectroscopic imaging of the temporal
      lobes between, during, and soon after nonconvulsive seizures in 20 patients with
      documented temporal lobe epilepsy, 5 patients with primary generalized epilepsy,
      and 2 patients with secondary generalized epilepsy. Our objective was to
      determine whether there were metabolic changes observable by magnetic resonance
      spectroscopic imaging during seizures and whether these changes were specific for
      focal or generalized nonconvulsive seizures. We found a significant increase in
      lactate to creatine plus phosphocreatine (lactate/creatine) values, reflecting an
      imbalance in energy supply and demand or an adaptation in response to ictal
      neuronal discharges, during and soon after complex partial seizures, but not
      during or soon after absence seizures associated with generalized epilepsy. In
      patients with temporal lobe epilepsy, the N-acetylaspartate resonance relative to
      creatine plus phosphocreatine was low in one or both temporal lobes, indicating
      neuronal loss or damage. This was not observed in patients with primary
      generalized epilepsy. The regions with abnormal lactate/creatine and N
      acetylaspartate/creatine values corresponded to the epileptogenic focus as
      defined by clinical-electroencephalographic investigation. There was no change in
      the N-acetylaspartate/creatine values in the temporal lobes between the
      interictal, ictal, or postictal states. We conclude that (1) partial seizures are
      associated with abnormally high lactate levels, but absence seizures are not, and
      (2) no short-term changes of N-acetylaspartate occur during or soon after complex
      partial seizures or absence seizures. These findings may be related to the lack
      of postictal confusion in patients with absence seizures, as well as with the
      more benign course of primary generalized epilepsy with nonconvulsive attacks.

PMID- 9005869
TI  - Reversible Schwann cell hyperplasia and sprouting of sensory and sympathetic
      neurites after intraventricular administration of nerve growth factor.
AB  - Substantial dysfunction and loss of cholinergic neurons occur in Alzheimer's
      disease (AD). Nerve growth factor (NGF) is a potent neurotrophic factor for
      cholinergic basal forebrain neurons, and the use of NGF to stimulate residual
      dysfunctional cells in AD is being considered. To define the effects of NGF on
      other cell populations in the brain, NGF was continuously infused into the
      lateral ventricle of rats for 7 weeks. At the end of treatment, Schwann cell
      hyperplasia and abundant sensory and sympathetic neurite sprouting were observed
      in the subpial region of the medulla oblongata and the spinal cord. Following
      withdrawal of NGF, the Schwann cell hyperplasia and sprouting of sensory and
      sympathetic neurites disappeared completely. These findings suggest that better
      temporal and spatial delivery systems for NGF must be explored to limit potential
      undesirable side effects while maintaining the survival and function of diseased
      basal forebrain cholinergic neurons.

PMID- 9005870
TI  - Skew deviation following vestibular nerve surgery.
AB  - Eighteen consecutive patients undergoing vestibular nerve surgery underwent pre-
      and postoperative examination of ocular motility. Five patients developed a skew
      deviation following surgery, with the lower eye on the operated side and an
      incomitant pattern of deviation in all cases. Three patients experienced diplopia
      lasting from 1 day to 6 months. The magnitude of skew deviation was increased by
      head tilt away from the operated side in only 1 case. The development of skew
      deviation was not determined by preoperative ocular alignment or binocular
      function, or any particular type or pattern of vestibular disease. There was an
      association with large changes in ocular torsion and subjective visual vertical,
      which correlated with lesser degrees of canal paresis to preoperative caloric
      testing on the operated side. No patient developed a head tilt postoperatively.
      There is a gradation of responses to surgical vestibular deafferentation in
      humans, skew deviation only occurring in patients suffering marked changes in
      subjective visual vertical and ocular torsion.

PMID- 9005871
TI  - Inclusion body myositis and paraproteinemia: incidence and immunopathologic
      correlations.
AB  - Serum from 70 patients with sporadic inclusion body myositis (IBM) was subjected
      to agarose gel immunofixation electrophoresis. The IgG extracted from 9 patients
      with monoclonal proteins, 3 without, and 2 control subjects and was purified,
      biotinylated, and applied to muscle biopsy sections for immunocytochemistry and
      to purified muscle protein fractions for immunoblots. Sixteen of 70 (22.8%)
      patients with IBM, compared with 2% of age-matched controls, had a monoclonal
      gammopathy characterized as IgG lambda in 9 patients, IgG kappa in 4, IgM kappa
      in 2, and IgA lambda in 1. The mean age of IBM patients with gammopathy was 60.6
      years (range, 35-77 years), compared with 66.1 years (range, 42-80 years) of the
      IBM patients without gammopathy. The IgG of the patients, more often than that of
      the control subjects, immunostained myonuclei and recognized various muscle
      proteins of 35 to 145 kd. We conclude that IBM, regardless of age, is frequently
      associated with monoclonal gammopathies, which often recognize various muscle
      components, especially myonuclei, suggesting disturbed immunoregulation.

PMID- 9005872
TI  - Patients homozygous for the 17p11.2 duplication in Charcot-Marie-Tooth type 1A
      disease.
AB  - Charcot-Marie-Tooth type 1A disease is an inherited sensorimotor neuropathy that
      is most often associated with a duplication of chromosome 17p11.2. This region
      contains the gene of the peripheral myelin protein 22 (PMP22), which is
      responsible by a gene dosage effect for the Charcot-Marie-Tooth type 1A phenotype
      with 17p11.2 duplication. We performed a clinical, electrophysiological, and
      genetic study of a consanguinous Charcot-Marie-Tooth type 1A family with 4
      affected siblings, 3 of whom were homozygous for the 17p11.2 duplication, the
      other a heterozygote. Comparison of phenotypes showed that the severity of the
      disease was variable among the homozygotes, one of whom was no more severely
      affected than the heterozygous sibling who was paucisymptomatic. These results
      suggest that the severity of the disease is not determined solely by the number
      of copies of the PMP22 gene.

PMID- 9005873
TI  - Stereotactic thalamotomy in tremor-dominant Parkinson's disease: an H2(15)O PET
      motor activation study.
AB  - Stereotactic thalamotomy is an effective treatment for severe drug-resistant
      tremor. The thalamus, however, facilitates motor activity, and thalamotomy would
      be predicted to inhibit movement-associated cortical activation. Two tremulous
      parkinsonian patients were studied with H2(15)O positron emission tomography
      before and after left ventralis intermedius thalamotomy. Subjects were scanned at
      rest and during performance of externally paced joystick movements in freely
      selected directions with the right hand. Thalamotomy relieved tremor but, as
      predicted, led to decreased activation of the left sensorimotor cortex, lateral
      premotor cortex, and parietal area 7 on hand movement.

PMID- 9005875
TI  - Mitochondrial function in muscle from elderly athletes.
AB  - The extent to which mitochondria are involved in the aging process is
      controversial; much of the reported decline in mitochondrial oxidations in human
      skeletal muscle may be due to disease and inactivity rather than age. To study
      true aging, mitochondrial respiratory chain function was studied in 9 young and
      12 elderly athletes. No significant deterioration with age was observed. If
      mitochondria are involved in aging, it must be through a more subtle mechanism
      than a global decline in respiratory chain activity.

PMID- 9005874
TI  - Adult-onset Krabbe's disease in siblings with novel mutations in the
      galactocerebrosidase gene.
AB  - Krabbe's disease or globoid cell leukodystrophy is a rare demyelinating disorder
      of the central and peripheral nervous systems, the diagnosis of which is based on
      clinical findings and the determination of low to absent functional activity of
      the enzyme beta-galactocerebrosidase. We report the presentation of late-onset
      Krabbe's disease in 2 siblings, a 17-year-old boy and his 16-year-old sister,
      both with marked deficiency of the enzyme beta-galactocerebrosidase. Only the
      older sibling manifested clinical signs and symptoms of the disease, while the
      younger sister remained asymptomatic to date. Molecular analyses disclosed the
      presence in this family of two novel single point mutations within the gene for
      galactocerebrosidase.

PMID- 9005876
TI  - X-linked vacuolated myopathy: membrane attack complex deposition on muscle fiber
      membranes with calcium accumulation on sarcolemma.
AB  - Cytochemical localization of calcium on muscle fibers from patients with X-linked
      vacuolated myopathy demonstrated strong sarcolemmal or vacuolar calcium deposits
      in histologically abnormal muscle fibers. All membrane attack complex-positive
      fibers demonstrated such calcium accumulation. Total content of calcium was
      significantly elevated in muscles from patients with X-linked vacuolated myopathy
      compared to control muscles. Taken together, these results suggest that calcium
      accumulation on sarcolemma could be probably secondary to membrane attack complex
      deposition on the cell surface.

PMID- 9005877
TI  - Collection and normal levels of the amyloid precursor protein in plasma.
AB  - The amyloid precursor protein is contained in platelet alpha granules and
      released with degranulation. Methods are described to control for amyloid
      precursor protein release from platelets during blood collection and processing.
      In normal subjects (n = 97; age range, 44-84 years), the average plasma level of
      amyloid precursor protein was 6.5 +/- 1.8 ng/ml.

PMID- 9005878
TI  - The role of MRI in clinical trials of multiple sclerosis: comparison of image
      processing techniques.
AB  - Magnetic resonance imaging (MRI) has received considerable attention in recent
      years over its potential for providing indices of multiple sclerosis activity and
      progression in clinical trials of new pharmaceuticals. The perceived advantages
      of MRI-derived measurements include greater objectivity, sensitivity, and
      reproducibility when compared with clinical rating scales. Clinical scales are
      also somewhat biased toward lesions affecting locomotion. However, the myriad
      permutations of MRI acquisition parameters, analysis methodologies, and disease
      indices demand careful consideration when employing MRI. Moreover, the use of MRI
      in research into the basic mechanisms of a disease may have different
      requirements than its use in a clinical trial setting. Consequently, a conference
      was held, sponsored by the US and Canadian multiple sclerosis societies, to
      review the present status of various MRI processing strategies and their
      potential role in clinical trials. Thirteen laboratories from North America and
      Europe as well as regulatory agencies and statistical consultants made formal
      presentations followed by extended discussion. This report presents the
      conclusions reached and recommendations for further action that emerged from the
      meeting.

PMID- 9005879
TI  - Trihexyphenidyl withdrawal encephalopathy.

PMID- 9005880
TI  - Early copper histidine therapy in classic Menkes disease.

PMID- 9005881
TI  - Admission prediction of expected final myocardial infarct size using weighted ST
      segment, Q wave, and T wave measurements.
AB  - Formulas for predicting final acute myocardial infarction (MI) size from ST
      segment deviation on an initial electrocardiogram were proposed by Aldrich et al.
      for anterior and inferior infarct locations. This study of 529 patients who did
      not receive thrombolytic therapy was performed to determine the effectiveness of
      the Aldrich formulas for predicting final QRS MI size; to propose new formulas
      for predicting final MI size using ST-segment deviation, Q wave, and T wave
      information in a development population of 322 patients; and to evaluate the new
      formulas in a randomly selected population of 207 patients. The Aldrich formulas
      achieved correlations with final infarct size of r = .40 for anterior and r = .43
      for inferior MI locations in the present population which are weaker than those
      previously reported. Formulas that consider electrocardiographic parameters in
      addition to ST-segment deviation were proposed for both anterior and inferior
      final MI size. In the test set of 207 patients, these models explained 16.9% and
      15.2% of the variation in final MI size for anterior and inferior locations
      respectively. They may prove useful in assessing the extent of myocardial salvage
      where interventions are to be tested.

PMID- 9005882
TI  - Spatial coherence: a new method of quantifying myocardial electrical organization
      using multichannel epicardial electrograms.
AB  - A new technique has been developed to quantify the organization of myocardial
      electrical activity. The spatial coherence technique employs the use of the
      magnitude-squared coherence (MSC) spectrum to analyze multichannel electrograms
      obtained during cardiac mapping. In this study, MSC values for all possible pairs
      of electrograms recorded from an epicardial plaque consisting of 112 electrodes
      were computed and systematically integrated to form a three-dimensional coherence
      surface, that is, a graphical representation of average coherence values versus
      the spatial orientation of one electrode to another. From this surface, two
      dimensional graphs of average coherence versus electrode separation distance were
      derived, and the data were fitted to an exponentially decaying curve. Two novel
      parameters indicative of myocardial organization were then extracted from the
      curves, the coherence length parameter and the coherence plateau parameter.
      Higher values for these parameters were hypothesized to reflect greater levels of
      organization of the rhythm. A total of 164 mapping sessions were performed on
      nine dogs. Three-second data segments of normal sinus rhythm (NSR) and
      ventricular fibrillation (VF) were analyzed by using spatial coherence. Coherence
      lengths were found to be significantly longer (24.3 +/- 13.4 vs 0.165 +/- 0.053
      mm, P = .0001) and coherence plateau values significantly higher (0.896 +/- 0.104
      vs 0.098 +/- 0.008, P = .0001) for NSR than for VF. In addition, one instance of
      ventricular tachycardia, a rhythm more organized than VF, had coherence parameter
      values greater than those for VF but less than those for NSR (coherence length =
      1.23 mm, coherence plateau value = 0.597). These results suggest that spatial
      coherence may be an effective means of quantifying the electrical organization of
      a particular cardiac rhythm. The advantages of this technique are (1) it extracts
      a single parameter from the vast amount of data that is generated in a typical
      mapping study, thus allowing easy characterization of different cardiac rhythms
      in terms of their level of organization, and (2) it does not require activation
      time detection, a process that is difficult when studying arrhythmias such as
      ventricular fibrillation.

PMID- 9005884
TI  - Torsade de pointes as a complication of subarachnoid hemorrhage: a critical
      reappraisal.
AB  - Subarachnoid hemorrhage is widely accepted as a potential cause of torsade de
      pointes (TdP), yet this putative etiologic relationship has never been
      systematically evaluated. We therefore undertook a MEDLINE search from 1966
      through 1993, with relevant back referencing, and identified 20 cases of TdP in
      the setting of subarachnoid hemorrhage. It was impossible in any of these cases
      (usually because of insufficient data) to completely exclude one or more
      alternative explanations for TdP, including congenital long QT syndrome,
      hypokalemia, hypomagnesemia, or drug-induced QT prolongation. Furthermore, of a
      total of 1,139 patients in 16 prospective series of subarachnoid hemorrhage with
      electrographic analyses, there were only five reported cases of TdP, all in
      patients with hypokalemia. Thus, extremely limited scientific data exist to
      support the notion that subarachnoid hemorrhage can be a distinct cause of TdP.
      Until more definitive evidence is available, the development of TdP in patients
      with subarachnoid hemorrhage is probably better characterized as a multifactorial
      phenomenon occurring in an acute, typically intensive care, setting.

PMID- 9005883
TI  - Do repolarization abnormalities in hypertrophic cardiomyopathy represent impaired
      fatty acid utilization? An observation with QRST isointegral maps.
AB  - To identify the clinical significance of the isointegral body surface map of the
      QRST interval (QRST map) and the occurrence of repolarization abnormalities in
      patients with hypertrophic cardiomyopathy (HCM), the QRST map and signal-averaged
      electrocardiogram were evaluated in 50 patients with HCM, in 33 of whom the
      results were compared with nuclear images both for radioiodine-labeled fatty acid
      metabolism and for radiothallium perfusion. The QRST departure map was used to
      determine two parameters of difference between patient and control recordings:
      the subnormal area (the number of lead points at which the departure index values
      were negative and lay more than 2 SDs from the mean of the normal control group)
      and the subnormal minimum (the absolute value of the minimum in the departure
      map). Late potentials were detected in 6 (12%) of the 50 patients; they were
      observed in 3 of the 5 patients with dilated-phase HCM but in only 3 (7%) of the
      other 45 patients. The subnormal area and minimum values were lower in
      nonobstructive HCM than in dilated-phase HCM. Of the 33 patients examined by
      myocardial imaging, 28 (33%) had a filling defect or decreased uptake, as shown
      on fatty acid metabolic images, and 10 of the 28 also showed abnormal myocardial
      perfusion images, while the 18 others showed normal perfusion images. These 28
      patients showed significantly larger values of the subnormal area and minimum
      than patients with normal results in both image tests, regardless of whether or
      not myocardial perfusion imaging abnormalities were present. The localization of
      filling defects or of decreased uptake presented in fatty acid metabolic images
      corresponded to the position of the minimum on the QRST departure map. These
      results suggest that the QRST map is useful for detection of repolarization
      abnormalities in HCM and that these abnormalities are highly related to impaired
      fatty acid utilization of the myocardium.

PMID- 9005885
TI  - Circadian heart rate variability rhythm in shift workers.
AB  - The objective of this study was to assess the influence of day-night cycle and
      sleep-awake period on the circadian pattern of heart rate variability (HRV).
      Twelve male oil refinery security shift workers, aged 39 +/- 7 years, were
      studied with 24-hour Holter monitor recordings during morning and night work
      periods. Hourly HRV parameters in the time and frequency domains were evaluated.
      For both shifts, all HRV parameters during awake or work periods were found not
      to be statistically different. In both day and night work shifts, the very low
      frequency and high-frequency components of HRV and the proportion of differences
      in successive R-R intervals greater than 50 ms increased during the sleep period,
      while the low frequency/high frequency ratio decreased. The low-frequency
      component in absolute units and the SD of the R-R interval did not show any
      variation in either shifts for the different periods. These results suggest that
      the circadian pattern of HRV seems to be predominantly related to sleep (supine)
      and wakefulness (standing) and remains independent of night-day cycle.

PMID- 9005886
TI  - Heart rate variability in myocardial ischemia during daily life.
AB  - The aim of this investigation was to evaluate the role of autonomic nervous
      activity before and during transient ischemic events. Forty-one ischemic episodes
      detected on Holter recordings were analyzed for heart rate and heart rate
      variability (HRV). A time-dependent index of HRV the windowed median successive
      difference, which is a continuous measure of respiratory sinus arrhythmia and
      therefore a marker of vagal efferent activity was used. A small window consisting
      of five beats, which represented one respiratory cycle, was chosen. This method
      permitted continuous assessment of short-term alterations of vagal modulation.
      With two exceptions, all ischemic episodes were preceded by an acute almost
      complete suppression of respiratory sinus arrhythmia. During the entire ischemic
      episode, HRV stayed at this reduced level, and preceding the end of the ischemia,
      it increased again. This suppression of intrinsic heart period variations
      reflects an almost complete withdrawal of modulated vagal outflow immediately
      before and during ischemic episodes. In 26 cases (63%), Fast Fourier
      Transformations were carried out when the heart rate was almost constant in two
      segments around the onset of ischemia. In the other 15 cases we did not perform
      Fast Fourier Transformations because there was no stationary stage in the data.
      High-frequency power always decreased drastically at the onset of ischemia,
      confirming a significant loss of modulated vagal activity (P < .01). The low
      frequency/high frequency ratio did not increase, indicating that sympathetic
      activity did not increase significantly at the onset of ischemia in about two
      thirds of our cases. The extent to which this suppression of modulated vagal
      activity reflects a similar suppression of vagal efferent activity is discussed,
      as well as whether this withdrawal of vagal outflow is cause or consequence of
      the ischemic event. The results suggest that a vagal depression may influence the
      onset of myocardial ischemia during daily life.

PMID- 9005888
TI  - Effects of activation sequence on monophasic action potential configuration in
      the dog.
AB  - The effects of altered activation sequence on the monophasic action potential
      (MAP) in in situ beating hearts are not known, although its effects on refractory
      periods are well documented. In nine anesthetized, open-chest dogs, complete
      atrioventricular block was produced, and the heart was driven by either right
      ventricular or left ventricular stimulation. The MAPs of the right and left
      ventricles were recorded by contact electrodes at cycle lengths of 1,000, 800,
      600, and 400 ms. The MAP configuration was evaluated with regard to the
      difference between phase 1 and phase 2 MAP amplitudes and MAP duration at 50 and
      90% repolarization. An MAP recorded from the ventricle that was being
      electrically stimulated was designated an ipsilateral ventricular stimulation,
      whereas the MAP recorded from the nonstimulated ventricle was termed a
      contralateral ventricular stimulation. The difference in amplitude and the 50%
      and 90% MAP durations for ipsilateral ventricular stimulation were consistently
      larger than for contralateral ventricular stimulation at all cycle lengths
      tested. Transient outward current did not appear to play a major role in
      producing such differences in MAP because intravenous treatment with 4
      aminopyridine, a blocker of transient outward current, did not affect the
      configuration of the MAP. These findings provide an insight on the influence of
      ventricular activation sequence on the shape of the transmembrane action
      potential.

PMID- 9005889
TI  - A new experimental model of isolated myocardial ischemic injury: ECG findings of
      acute isolated right ventricular ischemic injury.
AB  - A new experimental porcine model for creating selective ischemia of a specific
      part of the myocardium while the rest of the myocardium remains free of ischemia
      has been used to study the electrocardiographic (ECG) changes deriving from
      selective ischemia of the right ventricular (RV) free wall. A patch was stitched
      to the ventricle to produce selective myocardial ischemic injury. In a
      preliminary study of nine pigs, selective ischemia of the left ventricular free
      wall in five and of the RV free wall in four animals was induced, and a
      postmortem dye injection was performed to evaluate blood flow in the area of
      ischemia. In an ECG study of 20 pigs, the baseline ECG was recorded with use of
      the standard leads I-III, aVR, aVL, and aVF, left precordial leads (V1-V6), and
      leads V4R, V3H, and V4H and 1 hour after inducing ischemia, the ECG study was
      repeated. Our experimental model produced ischemic injury in which the location
      and surface area were known antemortem. In the 20 pigs, ST-segment changes were
      recorded in leads V1-V3, V3H, and V4H. In only four pigs (20%) was ST-segment
      elevation recorded in lead V4R. The results show that the ECG signs of selective
      ischemia of the RV free wall may imitate the signs of anterior or anterolateral
      infarction of the left ventricle. In this study, elevation of the ST-segment in
      lead V4R was not pathognomonic of for RV ischemia. This model is a new tool for
      studying hemodynamic and ECG changes of selective univentricular or biventricular
      ischemic injury.

PMID- 9005887
TI  - Implication of the negative U wave during dobutamine stress echocardiography.
AB  - Although the development of negative U waves during exercise is a highly specific
      marker for detecting coronary artery disease, their assessment during exercise is
      difficult. The clinical significance of the negative U wave during dobutamine
      stress echocardiography was investigated in 181 patients who had suspected
      coronary artery disease. Dobutamine-induced negative U waves appeared in 28
      patients (16%) during dobutamine infusion. Coronary angiography showed coronary
      artery disease in 114 of the 181 patients. The sensitivity and specificity of the
      negative U wave for detecting coronary artery disease were 22 and 96%,
      respectively, while the corresponding values for ischemic ST-T changes were 49
      and 76%, respectively. The negative U wave appeared during low-dose infusion of
      dobutamine (5-10 microg/kg/min) in 82% of the patients with this wave. In the 21
      patients who had both a negative U wave and an inducible regional wall motion
      abnormality during dobutamine infusion, the development of the negative U wave
      was either simultaneous with or earlier than that of the wall motion abnormality.
      Although its sensitivity was low, the negative U wave during dobutamine stress
      echocardiography is a highly specific marker for detecting coronary artery
      disease. Because of its earlier appearance as compared with that of the wall
      motion abnormality, the dobutamine-induced negative U wave may be considered to
      be an early and useful adjunctive sign for detecting coronary artery disease
      during dobutamine stress echocardiography.

PMID- 9005890
TI  - The normal vascular anatomy of the femoral head in adult man. 1953.

PMID- 9005891
TI  - Improved method for examination of microvascular structures in bone tissue.
AB  - Scanning electron microscopy of methylmethacrylate vascular corrosion casts was
      used for the morphologic examination of the microvascular system in bone. The
      methylmethacrylate used for vascular casting was prepared by prepolymerization
      with ultraviolet light. To approximate the viscosity of blood in the
      microcirculation, where the hematocrit of blood is lower than in the rest of the
      circulation, a viscosity between that of plasma and full blood was chosen for the
      casting material. Neither the ultraviolet prepolymerization of methylmethacrylate
      nor the choice of a viscosity this low has been used in microcorrosion casting in
      bone before. Further preparation of the tissue followed 2 directions: (1)
      complete maceration and decalcification of the specimens, thereby exposing all
      the vascular structures for detailed examination. By this procedure, it was
      possible to show detailed and sharp impressions of the vascular bed, and to show,
      for the first time, the vascular loop from a cutting cone; and (2) maceration
      without decalcification of the specimens, which is suitable for examination of
      relations between the microvascular system and the bone tissue. This technique
      enables studies of the role of the vascular system in bone remodeling and of the
      involvement of vascular structures in bone disorders. This improved technique for
      examination of microvascular structures in bone enables detailed studies of the
      vascular system and its relation to active remodeling sites in bone.

PMID- 9005892
TI  - Clearance of albumin by cortical bone and marrow.
AB  - Male Sprague-Dawley rats, approximately 300 g, were anesthetized. The jugular
      vein and carotid artery were cannulated and the left femoral vein was exposed.
      The femoral vein was then ligated, and 2 minutes later albumin, labeled with
      125I, was injected. The albumin was allowed to equilibrate in the vascular system
      for 3 minutes, and then 1 group of animals was euthanized. Further groups of
      animals were euthanized after 15, 30, and 60 minutes. Tibias were removed from
      both legs together with samples of muscle and liver. The tibias were separated
      into diaphyseal cortex, marrow, and proximal and distal ends. All tissue samples
      and terminal blood samples were counted for radioactivity, and volumes of
      distribution were calculated. In cortical bone the volume distribution increased
      from an initial value of 12.9 +/- 1.1 microL/g to 18.6 +/- 2.5 microL/g at 30
      minutes in the control leg (mean +/- standard error of the mean, n = 5). In the
      congested leg, the volume of distribution increased from 10.6 +/- 0.6 to 19.6 +/-
      2.1 microL/g during the same time interval. The difference in rate of increase
      between the congested and control leg was not statistically significant. Albumin
      seemed to equilibrate within 3 minutes within the marrow. The data are consistent
      with the hypothesis that macromolecular transport in the interstitial fluid of
      cortical bone is coupled to convectional flow from endosteal to periosteal
      surface. This data may help to understand mechanisms by which venous hypertension
      has been shown to stimulate bone growth and fracture repair, and also the
      distribution of bone density changes observed after prolonged exposure to
      microgravity.

PMID- 9005893
TI  - Assessment of ischemia and reperfusion injury.
AB  - Direct videomicroscopy of the rat cremaster muscle microcirculation supplemented
      by animal models of replantation, vascular crushing, and muscle function after
      injury and recovery were used to investigate the occurrence of reperfusion
      failure. It is evident that failure of blood reflow may be induced by multiple
      factors that can be grouped into categories of ischemia, intimal damage, and
      systemic or local responses, which are referred to as the no reflow triad. The
      components comprising the 3 sides of the no reflow triad can interact with one
      another in an intricate manner, and any single factor or combination of factors
      is capable of triggering the events leading to reperfusion failure. The
      pronounced regional nature of reperfusion injury and the direct relationship
      between the severity of the observed vascular alterations and increasing duration
      of ischemia have been documented. The dynamic changes and histopathology of the
      microcirculation included constriction of the arteries, swelling of endothelial
      and leukocytes, and erythrocyte rouleaux formation during ischemia. As ischemia
      duration was lengthened, the degree of these changes increased correspondingly.
      The changes on reperfusion were disruption of blood flow patterns, vortex
      formation, regional stasis, adhesion and migration of leukocytes, focal
      hemorrhage, edema, vasospasm, and platelet aggregation. The deleterious effects
      of systemic acidosis, interstitial hemorrhage, denervation, and prolonged venous
      occlusion were subsequently documented. The application of information gained
      from this series of laboratory experiments has resulted in continued improvement
      in the success rate in clinical microvascular surgery.

PMID- 9005894
TI  - Histopathologic study of veins in steroid treated rabbits.
AB  - Although arterial factors have been regarded as playing an important role in the
      pathogenesis of osteonecrosis, more attention has been given to venous factors
      because steroids cause an increase in the intraosseous pressure despite a
      decrease in blood flow in the femoral head. The authors examined changes in the
      veins of steroid treated rabbits. Forty rabbits were used: 30 rabbits (the
      steroid treated group) were injected with methylprednisolone acetate (4 mg/kg)
      weekly and 10 rabbits (the control group) were treated without steroids. The
      veins around the femoral head, ear veins, femoral veins, and inferior vena cava
      were obtained after 8 weeks of treatment, and the specimens were examined by
      immunohistochemical staining and electron microscopy. In the steroid treated
      group, proliferation of foam cells was observed in the intima of the vein in 7 of
      30 rabbits. Immunohistochemical studies, using monoclonal antibodies for smooth
      muscle cells and macrophages, showed that the foam cells were derived from smooth
      muscle cells. Electron microscopy showed damage to the endothelial cells and
      smooth muscle cells. These results indicated that corticosteroids damaged the
      venous system. It is suggested that steroid induced disturbance of the draining
      veins causes stasis and that steroids are an important factor in osteonecrosis of
      the femoral head.

PMID- 9005895
TI  - Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis.
AB  - In 31 patients with osteonecrosis (primarily of the hip), 74% had 1 or more
      primary coagulation disorders. In 18 patients, 15 (83%) who had coagulation
      disorders, the osteonecrosis was initially identified as idiopathic and was not
      associated with known underlying drugs (glucocorticoids) or diseases (alcoholism,
      sickle cell disease, Gaucher's disease). In 13 patients, 8 (62 %) who had
      coagulation disorders, the osteonecrosis was initially identified as secondary,
      and was associated with glucocorticoids in 12 patients, and with alcoholism in 1.
      The coagulation disorders included thrombhophilia (increased tendency to
      intravascular thrombosis) and hypofibrinolysis (reduced ability to lyse thrombi).
      Of the 18 patients initially thought to have idiopathic osteonecrosis,
      thrombophilia alone was found in 12% (resistance to activated protein C in 6%,
      low protein C in 6%), hypofibrinolysis alone was found in 50% (high
      lipoprotein(a) in 44%, low stimulated tissue plasminogen activator activity was
      found in 6%), and mixed thrombophilia hypofibrinolysis was found in 22%.
      Resistance to activated protein C was more common in these 18 patients than in
      healthy controls (11% versus 0%), as was high lipoprotein(a) (67% versus 20%). Of
      the 13 patients with secondary osteonecrosis, thrombophilia alone was found in 8%
      (low protein C), hypofibrinolysis alone was found in 30% (high Lp(a) in 15%, low
      tissue plasminogen activator activity in 15%), and mixed thrombophilia
      hypofibrinolysis was found in 23%. Low tissue plasminogen activator activity was
      more common in the 13 patients with secondary osteonecrosis than in controls (27%
      versus 7%), as was low protein C (23% versus 0%). In aggregate, these findings
      lead us to the speculation that primary, heritable thrombophilia or
      hypofibrinolysis causes thrombotic venous occlusion in the head of the femur,
      leading to venous hypertension and hypoxic death of bone (osteonecrosis).

PMID- 9005896
TI  - Hypercoagulability and hypofibrinolysis in primary osteoarthritis.
AB  - Histologic evidence of venous thrombosis and lipid abnormalities have previously
      been reported in osteoarthritis. Hypofibrinolysis has been recorded in patients
      with ischemic necrosis of bone, and it has been proposed as a major cause of
      osteonecrosis. This study determines whether systemic evidence of coagulation and
      lipid abnormalities could be detected in osteoarthritis. Global and specific
      tests were used to assess coagulability and fibrinolysis in 44 patients with
      degenerative osteoarthritis of the hip and 52 matched control subjects. In
      patients with osteoarthritis, an increase in factor VIIlc, increased platelet
      sensitivity over a range of adenosine diphosphate concentrations (0.05 micromol/L
      4 micromol/L) and elevated D dimer levels were found. Euglobulin clot lysis time
      was prolonged in this group and plasminogen activator inhibitor Type 1 activity
      was increased. Relative hyperlipidemia was observed in the osteoarthritis group,
      with increased cholesterol, low density lipoprotein cholesterol, and triglyceride
      levels. It is concluded that there is a hypercoagulable and prothrombotic
      condition in osteoarthritis, with hypofibrinolysis and indirect evidence of
      increased fibrin generation. The possible contribution of lipid abnormalities to
      hemostatic imbalance in osteoarthritis is discussed.

PMID- 9005897
TI  - Early magnetic resonance imaging and histologic findings in a model of femoral
      head necrosis.
AB  - The authors examined early magnetic resonance images and histologic findings of
      avascular necrosis of the femoral head in a canine model. The avascular necrosis
      of the femoral head model was surgically induced. Animals were euthanized at 3
      days, 1, 2, and 4 weeks, and the proximal femurs were retrieved. Magnetic
      resonance images and histologic sections were performed on each of the specimens
      obtained. Twenty-five mongrel dogs were studied, 4 dogs at 3 days and 7 dogs at
      each of the other intervals. Findings suggest that histologic changes may be seen
      as early as 3 days, with marrow edema and hemorrhage as early findings, and
      fibrous marrow transformation and appositional bone growth as later findings.
      Magnetic resonance imaging abnormalities did not occur until 1 week after injury
      and were seen in all animals by 4 weeks.

PMID- 9005898
TI  - Histomorphology and bone morphometry of the bone marrow edema syndrome of the
      hip.
AB  - From a prospective study of patients with MR imaging proven bone marrow edema
      syndrome of the hip, bone biopsies that were retrieved at core decompression
      treatment of 32 femoral heads (from 28 men and 3 women; age range, 25-63 years)
      were evaluated microscopically. The undecalcified microtome sections showed
      diffuse or spotty areas of interstitial and intrasinusoidal fluid in the marrow
      cavities, together with fat cell destruction or fibrovascular regeneration or
      both in exactly the regions exhibiting the magnetic resonance signals for bone
      marrow edema. The vital bone trabeculae in these edematous regions showed more or
      less continuous, partly osteoblast covered osteoid seams, and often, formation of
      irregular woven bone (microcallus), pointing to increased bone formation
      activity. Preceding or active osteoclastic resorption was rarely seen. Computer
      assisted bone morphometry revealed age related normal to elevated bone volume
      densities (above 20% bone volume of tissue volume); thus, no evidence for
      osteoporosis was present. In addition to increased osteoid volumes, a decreased
      maximal hydroxyapatite content and a shift to undermineralized bone was found by
      mineral densitometry of corresponding microradiographs, when compared with age
      matched femoral heads without bone pathology. These bone mineral changes, but not
      transient bone loss, could be the explanation for the more or less subtle and
      transient radiolucency in hips affected by bone marrow edema syndrome. Live
      trabeculae and active bone formation, however, point to increased repair
      capacity, which seems the key for the spontaneously reversible course of this
      syndrome. There is still controversy whether the bone marrow edema syndrome
      represents a distinct transient disease or an early reversible phase of avascular
      necrosis, but because of the similarities in histopathology reported for early
      classic avascular necrosis and bone marrow edema in the literature and in the
      authors' own material, a common pathophysiology is discussed for these seemingly
      different diseases.

PMID- 9005899
TI  - Contralateral hip in patients with unilateral nontraumatic osteonecrosis of the
      femoral head.
AB  - To clarify the risk of the development of osteonecrosis of the femoral head in
      the contralateral hip of patients with unilateral nontraumatic osteonecrosis of
      the femoral head, a followup study was performed using magnetic resonance
      imaging. Forty-six asymptomatic contralateral hips with no evidence of
      osteonecrosis on magnetic resonance imaging, in patients with unilateral
      osteonecrosis, were subjects of this study. The period from the onset of
      unilateral osteonecrosis to entrance in this study ranged from 1 month to 20
      years (mean, 3.1 years). There were 29 males and 17 females ranging in age from
      16 to 71 years (mean, 41 years). Twenty-three patients had previous steroid
      therapy for various conditions: 16 had alcoholism and 7 had no etiologic factors.
      The followup term ranged from 3 to 8 years (average, 5.5 years). During the
      followup period, 1 patient (2%) had a band of low signal intensity demarcating
      the lesion of normal fat intensity on T1 weighted images, which progressed to
      collapse of the femoral head. These results suggest that in unilateral
      osteonecrosis cases, osteonecrosis rarely develops in the contralateral hip that
      has appeared normal on magnetic resonance imaging. The contralateral hip with a
      negative magnetic resonance imaging scan is not in Stage 0 of osteonecrosis, but
      is normal.

PMID- 9005901
TI  - Modified Sugioka's osteotomy: more than 130 degrees posterior rotation for
      osteonecrosis of the femoral head with large lesion.
AB  - High degree posterior rotational osteotomy was performed on 31 hips with
      extensive osteonecrosis that were outside of Sugioka's indication. Among them, 18
      hips of 13 patients were reviewed at 24 to 94 months (mean, 42 months). The
      remaining 13 hips were excluded because the followup was less than 2 years. All
      hips had less than 1/3 of the posterior area intact preoperatively, which is out
      of the indication for traditional anterior rotational osteotomy. The posterior
      rotation applied to the femoral head was 130 degrees to 180 degrees (mean, 138
      degrees ). Furthermore, 10 degrees to 25 degrees of intentional varus position
      was added to the rotation (mean, 15.8 degrees). The preoperative intact articular
      surface of the loaded portion of the femoral head was 0% to 40% (mean, 6.9%) on
      anteroposterior radiograph, and it was extended postoperatively to a mean of
      80.3% (range, 53%-100%). Collapse was prevented in 17 hips that have remained
      pain free. The remaining 1 hip sustained secondary collapse and joint narrowing.
      Mean flexion was 105 degrees and abduction was 20 degrees. Postoperative
      angiography of 9 hips and bony scintigraphy of 17 hips indicated no findings
      implying impairment of blood supply. Despite a relatively short term experience,
      it is concluded that this technique was effective in the treatment of large
      necrotic lesions, especially for young patients.

PMID- 9005900
TI  - Core decompression for osteonecrosis of the femoral head in systemic lupus
      erythematosus.
AB  - A cross sectional study was performed to try to identify various demographic and
      radiologic risk factors for disease progression in 50 patients (79 hips) with
      corticosteroid associated osteonecrosis of the femoral head who had a core
      decompression. Thirty-one of the hips were in 18 patients who had systemic lupus
      erythematosus and were compared with the remaining group of 48 hips in 32
      patients who were taking corticosteroids for other reasons. All patients in the
      study had been taking greater than 30 mg of prednisone for at least 2 weeks at
      least 6 months before the onset of osteonecrosis. Patients underwent a core
      decompression and were then observed for an average of 12 years (range, 4-18
      years). Overall, 42 of the 79 hips (53%) had satisfactory outcomes. Of the 31
      hips in patients with systemic lupus erythematosus, 21 (68%) were converted to a
      total hip replacement. In the patients without systemic lupus erythematosus
      taking corticosteroids, 16 of 48 hips (33%) progressed to arthroplasty. A subset
      of 25 hips from each group (systemic lupus erythematosus and without systemic
      lupus erythematosus) were matched for age, gender, prednisone dose, Ficat and
      Arlet Stage, and length of followup. The matched group without systemic lupus
      erythematosus had 44% survival (11 of 25 hips), which was not statistically
      different when compared with the 36% survival (9 of 25 hips) found in the
      systemic lupus erythematosus group. The major risk factors for disease
      progression were late stage of disease (Stage III) at presentation and
      radiographic extent of the lesion (>200 degrees), regardless of diagnosis. None
      of the factors that have been found to be associated with osteonecrosis in
      patients with systemic lupus erythematosus could be associated with disease
      progression. Because cause seems to be less significant than the onset and extent
      of the disease, the clinician should make the diagnosis of osteonecrosis as
      promptly as possible so that treatment can be started at the earliest possible
      time, when it will be most efficacious.

PMID- 9005902
TI  - Total hip arthroplasty in patients with avascular necrosis of the femoral head: a
      2- to 10-year follow-up.
AB  - One hundred twenty-three total hip arthroplasties were performed in 85 patients
      with osteonecrosis of the femoral head. There were 51 males and 34 females with
      an average age of 45 years. The average followup time was 4.6 years with a range
      of 2 to 10 years. All femoral stems and 71 sockets were fixed with acrylic
      cement. Fifty-two of the sockets used were placed without cement. The average
      Harris hip score improved from 45 points preoperatively to 92 points at the time
      of last followup. Of the 246 components used, 6 acetabular and 4 femoral
      prostheses in 7 patients have been revised (4%). Two components (0.8%) were
      revised for infection, 2 (0.8%) for repeated dislocation, and 6 (2.5%) for
      aseptic loosening. There is current radiographic loosening in 3 acetabular and 2
      femoral components (2%). None of the noncemented acetabular components was either
      radiographically loose or revised. Within the subset of the 36 patients (52 hips)
      with a minimum 5-year followup (average, 6.6 years), 5 components (5%) were
      revised and 4 (4%) components are radiographically loose. The overall revision
      rate for cemented and hybrid hips at 2 to 10 years followup was 4%. The revision
      rate for hybrid hips alone was 2.5% in the entire series and 2% for hips with a
      minimum followup of 5 years. These results seem significantly better than
      previously reported. Using modern cement techniques and components, total hip
      arthroplasty can give excellent results in the young patient with avascular
      necrosis and may be the treatment of choice when reconstructive surgery is
      required.

PMID- 9005903
TI  - Uncemented total hip arthroplasty in osteonecrosis: a 2- to 10-year evaluation.
AB  - All patients undergoing uncemented total hip arthroplasty for end stage hip
      disease related to osteonecrosis of the femoral head were assessed prospectively
      between November 1983 and October 1992. The results of clinical evaluation using
      the Harris Hip score and radiographic assessment of fixation were analyzed to
      identify features of success or failure that may be unique to this population.
      Four different stem types and 4 different acetabular components were used. Sixty
      four patients had 98 hips implanted during the time of the study. The 42 male and
      22 female patients averaged 41 years of age (range, 21-69 years). Average
      followup was 87.3 months (7.3 years; range, 31-134 months). The cause of
      osteonecrosis was corticosteroids (42 hips), alcohol (27 hips), trauma (5 hips),
      and other (24 hips). Three patients (5 hips) have died and 4 patients (6 hips)
      are lost to followup. At last followup 65 of 87 hips (75%) remained
      radiographically stable and clinically functional, 18 of 87 (21%) have been
      revised, and 4 were failing (osteolysis). Of the 22 hips with revision or
      impending failure, 4 were for technical reasons on the femoral side and 18 were
      for acetabular wear. Patient factors such as weight or underlying disease state
      did not seem to influence the ability to achieve stable fixation or contribute to
      accelerated failure. Failures related primarily to problems of first generation
      devices including accelerated wear of acetabular components, technical issues of
      femoral component placement (undersizing of components or femoral fracture), and
      the use of noncircumferentially coated femoral components. Age may be a factor in
      early failure. This 10-year experience with total hip arthroplasty for the
      patient with end stage hip disease due to osteonecrosis suggests that uncemented
      total hip arthroplasty can be applied predictably to this younger, potentially
      more active patient population.

PMID- 9005904
TI  - Core decompression for avascular necrosis of the distal femur: long term
      followup.
AB  - Seventy-nine knees (45 patients) with a diagnosis of avascular necrosis of the
      distal femur treated between 1978 and 1989 were evaluated. All patients had a
      corticosteroid association (had been treated with >30 mg of prednisone for >2
      weeks predating by at least 6 months the onset of avascular necrosis). Thirty-two
      knees were managed with protected weightbearing and rest. Core decompression was
      performed at a minimum of 3 months after the onset of symptoms in another 47
      knees. The knees treated with protected weightbearing had an average asymptomatic
      period of only 11 months and all but 6 (18%) proceeded to total knee replacement
      within 6 years. Core decompression yielded good or excellent results in 73% of
      the knees at an average followup of 11 years (range, 4-16 years). Of the 13 knees
      with failed core decompression, 7 were asymptomatic for greater than 5 years. A
      subset of 26 knees from each group was matched for age, gender, diagnosis, Ficat
      and Arlet Stage, and length of followup. The matched noncore group had 23%
      survival as compared with 74% survival in the core group. This long term followup
      suggests that core decompression may slow the rate of symptomatic progression of
      avascular necrosis of the knee. In addition, core decompression may extend the
      symptom free interval in certain patients and may delay the need for more
      extensive procedures such as total knee arthroplasty.

PMID- 9005906
TI  - Anatomic considerations for a modified posterior approach to the scapula.
AB  - A modified posterior approach to the scapula was tested on 20 cadavers. The
      approach also was used in 2 cases with fractures involving the scapular neck and
      glenoid fossa. The incision is C shaped, with the convexity directed toward the
      lateral angle of the scapula. The posterior muscle fibers of the deltoid are
      reflected laterally after detaching them from their origin. The infraspinatus is
      mobilized without division to expose the posterior surface of the scapular neck
      and glenoid. Access to the rest of the posterior and the superior surfaces of the
      glenoid can be achieved by osteotomizing the acromion. The suprascapular
      neurovascular bundle is identified and protected at an average of 1.4 +/- 0.1 cm
      from the glenoid rim, where it is adherent to the spinoglenoid angle of the
      scapula. The circumflex scapular artery is protected at the lateral border of the
      scapula at an average of 2.8 +/- 0.5 cm from the inferior glenoid margin. The
      axillary nerve is protected inferior to the teres minor. However, care should be
      taken not to excessively retract the teres minor because the nerve lies in close
      proximity to the shoulder joint capsule.

PMID- 9005905
TI  - Familial calcification of the superior transverse scapular ligament causing
      neuropathy.
AB  - Two patients, members of the same family, were found to have entrapment of the
      suprascapular nerve from a calcified superior transverse scapular ligament. The
      chief complaint in both cases was pain and weakness and atrophy of the
      supraspinatus and infraspinatus muscles. The nerve entrapment was confirmed by
      electromyographic studies and required surgical decompression to relieve the
      symptoms in both patients. Release of the entrapped nerve resulted in complete
      pain relief and full return of strength at 1-year followup.

PMID- 9005907
TI  - Fatigue analysis of human reinnervated muscle after microsurgical nerve repair.
AB  - The reinnervated elbow flexors, biceps, and brachialis muscles were compared with
      the elbow flexors on the healthy opposite side in terms of muscle strength and
      fatigue in 10 patients who sustained sequelae of a unilateral posttraumatic
      brachial plexus palsy. The patients had recovered an active elbow flexion against
      resistance after microsurgical nerve repair. The patients were reviewed with an
      average postoperative followup of 12 years (range, 7.5-16 years). Despite a
      statistically significant difference in maximum isometric force, this study
      showed that after peripheral nerve repair, a partially reinnervated muscle has
      the same characteristics of fatigue and endurance as a normally innervated
      muscle, if these muscles exert the same percentage of their own maximum force.

PMID- 9005908
TI  - Advanced cement technique improves fixation in elbow arthroplasty.
AB  - An in vitro study was conducted to assess the efficacy of advanced cementing
      techniques in the fixation of the humeral stem in elbow arthroplasty. Sixteen
      fresh frozen cadaveric distal humeri were prepared to accept an acrylic sham
      humeral stem. Conventional cementing technique using doughy cement manually
      inserted and packed was performed in 8 specimens. The advanced cementing
      technique, consisting of canal irrigation, brushing and drying with gauze, canal
      plugging, and low viscosity cement pressurization with a delivery system was
      performed in the other specimens. All humeri subsequently were sectioned into 10
      mm thick sections, photographed, and digitized to quantify the perimeter and area
      of the stem, cement mantle, corticocancellous junction, and cement voids. The
      degree of cement filling, determined from the area fraction of cement to the
      total available area within the corticocancellous junction, was significantly
      greater in the advanced group compared with the conventional group. Mechanical
      assessment of the specimens consisted of a push out load to failure test of the
      cement mantle from bone. For all locations in the distal humerus, the failure
      load and failure stress in the advanced group was significantly greater than the
      conventional group. It is concluded that development of an effective cement
      restrictor and application of advanced cement techniques in vivo should improve
      the initial fixation of the humeral component and may decrease the incidence of
      aseptic loosening associated with elbow arthroplasty.

PMID- 9005909
TI  - Failure mechanisms of anatomic porous replacement I cementless total hip
      replacement.
AB  - The APR-I Hip System was designed for metaphyseal bone attachment by proximal
      patch porous coating and the acetabular component was a hemisphere fixed with
      screws. The results of 100 consecutive primary total hip arthroplasties performed
      with the APR-I were studied in patients still alive after an average of 6.7
      years. The selection of hips for implantation of this hip system was limited to
      those patients in whom a satisfactory intraoperative fit could be obtained. This
      resulted in a distribution of patients such that 75% were younger than age 65
      years and only 15% had osteoporotic bone. The revision rate was 16% with a
      mechanical failure rate of 11%. Seventy percent of hips had progressive loss of
      fixation. loss of femoral component fixation was correlated with younger patient
      age, higher patient activity level, metaphyseal fill of less than 90%, and
      increased polyethylene wear and osteolysis. Eighty-nine percent of hips
      maintained femoral neck contact with the porous coated collar. The acetabular
      component was well fixed in 97% of hips. The failure rate of the APR-I stem is
      unacceptably high and this stem is no longer used by the authors.

PMID- 9005910
TI  - Effect of epidural analgesia on venous blood flow after hip arthroplasty.
AB  - The effects of postoperative epidural infusions using local anesthetic and
      narcotic were assessed in reference to lower extremity blood flow. Nineteen
      patients who underwent unilateral total hip arthroplasty were randomly assigned
      to receive a postoperative epidural infusion of either 5 microg/ml fentanyl or 5
      microg/ml fentanyl plus 0.125% bupivacaine at a rate of 10 ml per hour. The
      infusions were started after complete resolution of the operative epidural
      blockade. Femoral venous blood flow volume and velocity were measured above and
      below the saphenous vein bifurcation using an Acuson #128XP/10 computed
      sonography system (duplex ultrasound) and proprietary software. Femoral venous
      blood flow was not affected by the type of infusion and did not increase during
      the study period. However, femoral venous blood flow volume increased 50% after
      active flexion and extension of the foot, 10 times in quick succession. The
      addition of bupivacaine (a local anesthetic that blocks sympathetic afferent
      nerves) to a postoperative epidural infusion does not augment blood flow from the
      deep veins of the leg after total hip arthroplasty. Alternatively, lower
      extremity skeletal muscle activity significantly enhances femoral venous blood
      flow and may be a useful adjunct in deep venous thrombosis prevention.

PMID- 9005911
TI  - Short term prophylaxis against heterotopic bone after cementless hip replacement.
AB  - The aim of the current study was to reveal whether 7 days of indomethacin
      treatment sufficiently prevents heterotopic ossification after cementless total
      hip arthroplasty. One group received indomethacin for 14 days (n = 102), and the
      second for 7 days (n = 99) after cementless total hip arthroplasty. At followup 1
      year postoperatively, the average Harris Hip Score was 91 points in the 14-day
      treatment group and 89 points in the 7-day treatment group. The incidence of
      heterotopic ossification as outlined by Brooker was similar in both groups.
      Ninety-six patients in the 14-day treatment group had heterotopic ossification
      Grades 0 or 1, and 6 patients had Grade II heterotopic ossification; whereas in
      the 7-day treatment group, 95 patients had Grades 0 or 1 heterotopic ossification
      and 4 patients had Grade II ossification. None of the patients had Grades III or
      IV heterotopic ossification. In the 14-day treatment group, headache, dizziness,
      or gastritic disorders develop in 10 patients, and in the 7-day treatment group,
      7 patients had these effects. This study shows that treatment with 100 mg
      indomethacin daily for 7 days is not significantly different than 14 days of
      treatment for the prevention of formation of severe heterotopic ossification
      after cementless hip arthroplasty.

PMID- 9005912
TI  - Radiographic analysis of a cemented titanium alloy femoral component.
AB  - Proximal femoral cortical bone remodeling was evaluated radiographically about a
      1 piece cemented titanium alloy femoral prosthesis implanted with modern cement
      techniques and was compared with one described previously in which early cement
      techniques and a stainless steel stem were used. Two hundred twenty-six total hip
      replacements (196 patients) were observed for an average of 6.3 years (range, 5
      10 years). Analysis of all hips revealed that the ratio of cortical thickness to
      that of the overall femoral bone diameter did not change significantly about the
      periprosthetic bone throughout the length of the study. Cortical hypertrophy and
      atrophy occurred at rates similar to those seen with the early cement techniques.
      Distal fusiform cortical hypertrophy and the formation of osteosclerotic
      (reactive) lines at the bone cement interface occurred at approximately half the
      rate using modern cement techniques. In addition, cortical atrophy was associated
      with the formation of these reactive lines, the occurrence of osteolytic lesions,
      and progressive bone cement interface radiolucencies. Although periprosthetic
      cortical atrophy occurred at rates similar to those reported previously,
      important differences were noted between the findings of this study and the
      earlier study; these differences most likely were a result of cement technique or
      the prosthesis.

PMID- 9005914
TI  - Anatomic considerations for uncovertebral involvement in cervical spondylosis.
AB  - Morphometric analysis of 54 dry cervical spines from C3 to C7 (a total of 270
      cervical vertebrae) and bilateral dissection of 10 anatomic specimen cervical
      spines were performed. The uncinate processes were significantly higher at C4 to
      C6 (5.8 +/- 1.1 mm to 6.1 +/- 1.3 mm) levels than at C3 or C7 levels. The
      anteroposterior diameter of the intervertebral foramina was smaller at the C4,
      C5, and C6 levels compared with that at the C3 or C7 levels. The length of nerve
      root between the lateral border of dural tube and medial border of vertebral
      artery gradually increased from C3 (3.3 +/- 1.1 mm) to C7 (8.1 +/- 2.1 mm). A
      combination of higher uncinate process, smaller anteroposterior diameter of
      intervertebral foramina, and longer course of nerve roots in close proximity of
      the uncovertebral joints at the C4 to C6 levels may explain the predilection of
      nerve root compression by uncovertebral osteophytes at these levels. The distance
      from apex of the uncinate process to medial border of the transverse foramen
      gradually increased from C3 (1.7 +/- 0.8 mm) to C7 (3.3 +/- 1.0 mm), which may
      predispose the midcervical level to compression of the vertebral artery by
      laterally projecting uncovertebral osteophytes.

PMID- 9005913
TI  - Posttraumatic syringomyelia: a review of 21 cases.
AB  - A retrospective study was conducted on 21 consecutive patients with combined
      clinical and radiologic evidence of posttraumatic syringomyelia. Medical records
      and radiologic studies were reviewed to determine the following: age at injury,
      mechanism of trauma, spinal column injury and resultant neurologic deficit,
      latency period between injury and clinical manifestations of posttraumatic
      syringomyelia, clinicoradiologic findings of posttraumatic syringomyelia, and
      results of treatment. The patients were found uniformly to have sustained
      significant trauma (gunshot wounds, falls, or vehicular accidents) with marked
      neurologic dysfunction at the time of injury. Latent periods ranged from 1 month
      to 23 years. The most commonly presenting symptoms were radicular pain,
      spasticity, sensory loss, hyperhidrosis, and weakness. The most common physical
      findings were spasticity, hypesthesia, and weakness. Long term followup was
      obtained in 17 (81%) of the cases and suggested a higher rate of satisfaction
      among patients treated with surgical decompression of the syrinx. Radicular pain
      and sensory disturbance responded most predictably to surgical intervention,
      whereas spasticity responded least favorably. It is concluded that posttraumatic
      syringomyelia is a potentially disabling but treatable late complication of
      spinal injury, warranting a high index of suspicion among physicians who observe
      patients with such trauma.

PMID- 9005915
TI  - Changes in osteosclerosis of the osteoarthritic knee after high tibial osteotomy.
AB  - Radiographically demonstrated osteosclerosis was quantitatively evaluated in
      knees with medial compartmental osteoarthritis by dual xray absorptiometry. Bone
      density was measured in various areas of 144 knees with medial compartmental
      osteoarthritis, 23 knees of which were treated with high tibial osteotomy. The
      bone mineral density of the medial femoral and tibial condyles was greater than
      that of the lateral femoral and tibial condyles in all knees with medial
      compartmental osteoarthritis. The ratios of bone mineral density of the medial
      condyles to that of the lateral condyles were found to increase significantly
      with the progression of osteoarthritis. There was a significant positive
      regression line correlation between those ratios and the increase of varus
      deformity as expressed by the standing femorotibial angle. The former were
      calculated to be 1.0 when the latter was nearly 170 degrees (10 degrees anatomic
      valgus angulation). The ratio of bone mineral density of the medial femoral
      condyles to the lateral femoral condyles decreased sharply in all 23 knees within
      1 year after high tibial osteotomy.

PMID- 9005917
TI  - Paraarticular osteochondroma of the knee: report of 2 cases and review of the
      literature.
AB  - Paraarticular osteochondromas are unusual osteocartilaginous tumors that arise in
      the soft tissue adjacent to a joint. Their pathogenesis and classification are
      controversial, and worrisome histologic features make the distinction from
      chondrosarcoma difficult on morphologic grounds alone. Two cases of paraarticular
      osteochondroma of the knee arising in patients 66 and 75 years of age are
      reported in this study. Although the exact biologic nature of these tumors is not
      well characterized, limited data suggest that they will behave in benign fashion,
      similar to soft tissue chondromas. Paraarticular osteochondromas should be
      recognized to avoid unnecessarily aggressive surgical management.

PMID- 9005916
TI  - Critical evaluation of anterior drawer measurement methods in the ankle.
AB  - Anterior drawer testing has been used to assess the integrity of the lateral
      collateral ligaments, most notably the anterior talofibular ligament. Various
      radiographic measurement methods have been designed to assess sagittal plane
      talar displacement under stress. This investigation examined the anterior drawer
      test in 8 fresh frozen lower extremity cadaver specimens. Each specimen was
      mounted on a fabricated test frame and instrumented with a linear variable
      displacement transducer to directly measure talar displacement during stress
      application. Lateral radiographs were taken before and during stress application.
      Two radiographic measurement techniques (concentric circle and plafond to dome),
      each corrected for magnification effect, were compared with directly measured
      talar displacement values with the foot placed in 20 degrees plantar flexion.
      There were no significant differences between talar displacements measured
      directly and radiographically using the concentric circle method. Significant
      differences were found between directly and radiographically measured
      displacements using the uncorrected plafond to dome method. Subtracting the
      unstressed from the stressed tibiotalar distance for the plafond to dome method
      resulted in no significant difference from directly measured talar displacement
      values. It is not necessary to correct talar displacement values obtained when
      using the concentric circle method.

PMID- 9005918
TI  - Accuracy of the Jamshidi trocar biopsy in the diagnosis of bone tumors.
AB  - Obtaining a histologic diagnosis is crucial in patients presenting with a tumor
      or a tumorous condition of the bone. The incisional surgical and the closed
      trocar biopsy are the most frequently used techniques for obtaining a
      representative tissue sample for histologic evaluation. This study reports on the
      reliability of 270 Jamshidi trocar biopsies performed on 258 patients with
      osseous tumors and tumorlike lesions. All patients were evaluated clinically and
      radiographically by a team consisting of an orthopaedic surgeon, a radiologist,
      and a surgical pathologist. In nearly all cases the biopsy and the resection were
      performed by the same orthopaedic surgeon. The biopsy site was determined in
      accordance with the planned subsequent resection surgery. Overall, an accurate
      diagnosis could be reached in 90.7% of the total number of 270 Jamshidi biopsies
      and in 95% of the 258 patients. The failure rate of the 270 biopsies was 9.3%. No
      specific contraindications with regard to the kind of lesion were found. Except
      for the pelvis, the localization of the lesion did not influence the rate of
      success. The high accuracy of the trocar biopsy, combined with the advantages of
      this technique over the incisional surgical biopsy, makes it a safe, fast, and
      adequate technique for obtaining a histologic sample of a bone tumor.

PMID- 9005919
TI  - Treatment of tibial pilon fractures using ring fixators and arthroscopy.
AB  - Twenty-one patients with tibial pilon fractures were treated with ring fixators
      and arthroscopy. There were 2 Type I, 14 Type II, and 5 Type III fractures using
      the Ruedi classification. In Ruedi Types I and II fractures, ring fixators were
      applied to the tibia and foot, and closed reduction was performed, monitoring the
      quality of the reduction with an image intensifier. When the quality of the
      reduction was questionable, arthroscopy was used, and if necessary, the reduction
      was readjusted. Olive wires were used to achieve reduction and fixation. In all
      Ruedi Type III fractures and 4 Ruedi Type II injuries, a limited open reduction
      was performed instead of arthroscopy. Approximately 8 weeks after the operation,
      the foot mounting was removed. The ring fixators were removed between 16 and 28
      weeks. Bony union was achieved in all but 1. At an average followup of 37 months,
      there were 15 good, 4 fair, and 2 poor results. There were 8 cases of pin tract
      infection, and 1 patient had loss of reduction. There were no cases of deep wound
      infection. It was concluded that ring fixator and adjunctive arthroscopy is safe
      and effective in the management of tibial pilon fractures.

PMID- 9005920
TI  - Growth and growth prediction of the fibula.
AB  - Growth prediction data and graphs have not been available previously for the
      fibula. In this report, this information is wholly derived from a longitudinal
      radiographic study of growth in children. Teleradiographs of the tibia and fibula
      in 244 children (123 boys and 121 girls) were made at 6-month intervals from age
      7 until skeletal maturity. Length measurements determined the growth of the
      fibula. The subjects were healthy well nourished middle class Americans, mostly
      of Northwest European descent. Growth occurring at the fibular growth plates was
      determined by the relationship to the tibia. The contribution of the proximal and
      distal growth plates to total length was determined by multiplying the percentage
      of growth occurring at each age by the longitudinal growth remaining. Graphs then
      were constructed using the logarithmic adjustment of Colin Moseley to produce a
      straight line graph. The proportion of growth occurring at the proximal and
      distal growth plates is not equal. More growth occurs at the proximal growth
      plate of the fibula than at the proximal growth plate of the tibia. The overall
      growth contribution of the proximal fibular growth plate is 61% compared with 57%
      for the proximal tibia. The graphs provided allow accurate prediction of fibular
      growth.

PMID- 9005921
TI  - Results after femoral and innominate osteotomy in Legg-Calve-Perthes disease.
AB  - In a retrospective study of the surgical management of Legg-Calve-Perthes
      disease, 16 femoral osteotomies (Group A) and 18 innominate osteotomies (Group B)
      were compared Smith regard to clinical and radiographic results. All hips were
      classified preoperatively as Catterall Group 3 or Group 4. The average followup
      period was 6 years in Group A and 8 years in Group B. The clinical results were
      the same in the 2 groups and all patients were asymptomatic in the affected
      hip(s) during daily activity. The radiographic results were also the same in the
      2 groups with regard to measurements of the sphericity of the femoral head
      (Mose's index and epiphyseal quotient) but the coverage of the femoral head by
      the acetabulum (center edge angle) was better in the innominate osteotomy group.

PMID- 9005922
TI  - Tibial nerve entrapment at the tendinous arch of the soleus: a case report.
AB  - Tibial nerve entrapment at the tendinous arch of the soleus has not been
      reported. A 58-year-old woman suffered from pain in the sole of her left foot,
      which was aggravated by active plantar flexion or passive extension of the ankle.
      Computed tomography and magnetic resonance imaging revealed a hypertrophic lesion
      in the left popliteus muscle. The tibial nerve was pushed posteriorly by the
      lesion and compressed by the arch of the soleus. The arch of the soleus was
      divided surgically. Pain was resolved immediately after the surgery, and
      significant neurologic recovery was observed 1 year after the surgical treatment.
      This condition must be recognized as a different clinical entity than either
      lumbar radiculopathy or tarsal tunnel syndrome.

PMID- 9005923
TI  - Analgesia for emergency centers' orthopaedic patients: does an ethnic bias exist?
AB  - Several prior studies have demonstrated that Hispanics treated in some emergency
      centers were prescribed less analgesia than white patients with similar extremity
      trauma. The purpose of this study was to determine if other institutions had a
      similar experience with regard to undermedication of certain ethnic groups. Two
      cohorts were studied, 1 adult and 1 pediatric group. The adult group consisted of
      84 patients seen at Maricopa Medical Center, Phoenix, Arizona, between January 1,
      1992, and December 31, 1992, who were treated for isolated long bone fractures
      requiring a closed reduction. The pediatric group consisted of 63 children
      younger than 16 years, seen between January 1, 1992, and April 30, 1993, with
      isolated distal radius or ulna fractures requiring a closed reduction. Results
      indicated that Hispanics were not likely to be undermedicated for fracture
      reduction in this level I trauma emergency center compared with whites. It is
      thought that a hospital with a larger populations of underrepresented minorities
      may be more sensitive than other private institutions.

PMID- 9005924
TI  - Acetabular strains produced by oversized press fit cups.
AB  - The purpose of this study was to determine the amount of acetabular deformation
      that occurs when acetabular components of different sizes are press fit. The
      change in acetabular volume was calculated for 1- to 3-mm oversized cup diameters
      with acetabuli ranging from 40 to 80 mm. An axisymmetric finite element model was
      used to determine the maximum acetabular strain that occurs when oversized cups
      are inserted in different acetabuli. The highest acetabular strains occur at the
      cup periphery, indicating that the resultant compressive force between the
      lateral pelvis and cup enhances press fit stability. In addition, higher maximum
      strains occur when the same millimeter amount of oversizing is used in a small
      compared with a large acetabulum. When a constant millimeter increment in cup
      oversizing is used, there may be a greater risk of pelvic fracture in a small
      acetabulum and a greater risk of inadequate press fit stability in a large
      acetabulum. To achieve the same amount of acetabular deformation and magnitude of
      strain, more oversizing is needed in a large acetabulum and less oversizing is
      needed in a small acetabulum. These results suggest that 1 mm of oversizing
      should be used for cups that are less than 52 mm in diameter, 2 mm of oversizing
      should be used for cups from 52 to 76 mm in diameter, and 3 mm of oversizing
      should be used for cups that are more than 76 mm in diameter.

PMID- 9005925
TI  - Osteochondral allografts with an intramedullary muscle flap in rabbits.
AB  - A model for hemijoint reconstruction using partially demineralized and
      lyophilized osteochondral allografts combined with an intramedullary muscle flap
      is described. The proximal 2/3 of the humerus was resected in 10 rabbits. The
      remaining defect was reconstructed with either a control lyophilized
      osteochondral allograft or a lyophilized allograft with a muscle flap filling the
      marrow cavity. Graft healing was followed by serial radiographs and magnetic
      resonance imaging. The grafts were harvested at 5 weeks for histologic analysis.
      By 5 weeks, 4 of 5 control allografts had fractured. In contrast, only 1
      allograft with an intramedullary muscle flap showed evidence of a cortical break.
      Magnetic resonance imaging of control allografts showed a persistent large dead
      space within the marrow cavity and callus formation only at the outer cortical
      surface. Magnetic resonance imaging of allografts with an intramedullary muscle
      flap showed muscle obliterating the marrow cavity and areas of callus formation
      at both the outer and inner cortical surfaces. Histologically, graft
      incorporation was occurring at the outer cortical surface of the control
      allografts. In contrast, graft incorporation was occurring at both the outer and
      inner cortical surfaces of the allografts with an intramedullary muscle flap. The
      articular surface of the control allografts was severely degenerated. In
      allografts with an intramedullary muscle flap, the articular surface was
      smoother. Joints reconstructed with allografts with an intramedullary muscle flap
      had a significantly better range of motion at 5 weeks compared with control
      allografts. These results suggest that an intramedullary muscle flap can improve
      the functional results of joints reconstructed with partially demineralized and
      lyophilized osteochondral allografts by providing both vascularity and an
      increased population of mesenchymal stem cells capable of responding to bone
      morphogenetic proteins that reside in the partially demineralized allograft.

PMID- 9005926
TI  - Experimental hematogenous osteomyelitis by Staphylococcus aureus.
AB  - To assess bone marrow lodgement of bacteria that produce osteomyelitis, 10(6)
      colony forming units of 16 nonhemolytic strains of Staphylococcus aureus was
      injected intravenously into mice. Eleven of 16 strains showed bone marrow
      lodgement without the death of mice. The M-138 strain induced osteomyelitis in
      100% of the mice. Furthermore, the difference of compact colony forming active
      substance activity between bone marrow lodgement and nonlodgement strains was
      statistically significant. Compact colony forming active substance, which is an
      alkali stable polysaccharide located on the cell surface of Staphylococcus aureus
      strain, caused compact formation of the strains in serum soft agar or fibrinogen
      soft agar, and it clotted animal plasma. These results suggest that bacterial
      factors are important for bacterial lodgement at the onset of staphylococcal
      hematogenous osteomyelitis.

PMID- 9005927
TI  - Aggregate degradation by growth plate proteases.
AB  - For long bone growth to occur, calcification of the matrix must begin in the
      lower hypertrophic zone of the growth plate. It generally is accepted that
      physeal proteoglycans help regulate mineralization, and that, at least in vitro,
      smaller proteoglycan fragments are less inhibitory of mineral formation. It also
      has been shown that proteoglycan degrading enzymes are concentrated in the
      hypertrophic zone, where calcification occurs. Thus, one can hypothesize that
      these enzymes are involved in the calcification process. Proteoglycans appear
      mainly as the aggregate form in the physis, and this study demonstrates the
      ability of the naturally occurring physeal enzymes to degrade proteoglycan
      aggregate, without first disaggregating it. Because the matrix constituents
      probably limit hypertrophic cell size and shape, this degradation may have some
      relationship to the rate of growth of the physis.

PMID- 9005928
TI  - Changes in the permeability and histologic findings of rabbit menisci after
      immobilization.
AB  - The knees of mature rabbits were immobilized for 2 to 8 weeks by a long leg cast
      to examine adverse effects on the meniscus. Some joints were remobilized for 1 to
      4 weeks after an immobilization period of either 6 or 8 weeks. Horseradish
      peroxidase was injected into knee joints, and the degree of permeation into the
      meniscus was visualized with diaminobenzidine tetrahydrochloride. Menisci were
      examined histologically by light and transmission electron microscopic study.
      Injected horseradish peroxidase permeated all areas of the meniscus in
      nonimmobilized joints. However, permeability of horseradish peroxidase gradually
      decreased with increasing time of immobilization and was restricted to the
      superficial layer of the meniscus in the 8-week immobilization group.
      Degenerative changes in the deep layers of the meniscus were noted in the 6-week
      immobilization group: 8 weeks of immobilization induced additional degenerative
      changes. Although permeability of horseradish peroxidase gradually recovered with
      remobilization, the degenerative changes remained in the deep meniscal layer in
      the 8-week immobilization group, even after 4 weeks of remobilization. These
      results clearly show that long-term immobilization of the knee joint causes
      adverse changes in the meniscus.

PMID- 9005929
TI  - Particulate bioglass compared with hydroxyapatite as a bone graft substitute.
AB  - Bioactive ceramics, notably hydroxyapatite, have been used clinically in various
      situations in which bone augmentation and restoration are required. Particulate
      material has been used either alone or in conjunction with freeze dried or
      autologous bone, with variable clinical success. In this study a bioactive glass,
      45S5 Bioglass, has been compared with hydroxyapatite in an animal model to
      discover whether the 2 major disadvantages of hydroxyapatite may be overcome.
      These are the difficulty of placing and retaining the particulate in the defect
      and the length of time needed before full bony restoration is achieved. Bioglass
      is shown to be easy to manipulate and hemostatic and allows full restoration of
      bone in 2 weeks, rather than the 12 weeks needed for the particulate
      hydroxyapatite to produce a comparable response. The Bioglass particulate is used
      up in the process, and any problems that may be associated with the production of
      a composite of bone and biomaterial are avoided in the fully restored bone. In
      any procedure that requires bony augmentation, this rapid response to Bioglass is
      expected to provide a clinical advantage.

PMID- 9005930
TI  - Influence of temperature and vacuum mixing on bone cement properties.
AB  - To analyze the influence of varying viscosity and mixing temperature (22 degrees
      C and 6 degrees C) on macro- and microporosity, density, and compressive strength
      in vacuum mixed bone cement, high, medium, and low viscosity cement were mixed in
      2 vacuum mixing systems and compared with bowl mixing at atmospheric pressure. At
      22 degrees C, vacuum mixing significantly reduced void volume to less than
      approximately 3 per mill. The reduction was most pronounced in low viscosity
      cement. Microporosity also was reduced in all cements by vacuum mixing and to
      highest degree in low viscosity cement. At 6 degrees C the reduction of
      micropores was more pronounced in high viscosity cement. In medium and especially
      low viscosity cement, the prechilling gave an increased number of micropores.
      Cement density also was significantly reduced in low viscosity cement at 6
      degrees C. Vacuum mixing significantly increased compressive strength by
      approximately 15% in all cement types (30 days). The temperature did not
      significantly influence compressive strength, but low viscosity cement generally
      was stronger when mixed at 22 degrees C. It is concluded that vacuum mixing
      improves cement quality. However, the temperature influences the final result; in
      particular, low viscosity cement should not be mixed after prechilling to 6
      degrees C.

PMID- 9005931
TI  - Calcitonin gene related peptide enhances bone colony development in vitro.
AB  - Recent evidence suggests that sensory nerve fibers of the dental pulp secrete
      calcitonin gene related peptide alpha exactly where secondary or tertiary dentin
      is mineralized. In addition, calcitonin gene related peptide raises the level of
      cyclic adenosine monophosphate in osteoblasts, indicating a potential effect on
      secretory activity in bone. Because calcitonin and calcitonin gene related
      peptide are formed from the same gene, the authors tested whether calcitonin gene
      related peptide or calcitonin has an osteogenic potential in vitro. To this end,
      0.01, 0.1, and 1 microg/ml of salmon calcitonin or rat calcitonin gene related
      peptide in Bigger, Gwatkin, Jackson b medium was added daily to 3 x 10(6) rat
      light density bone marrow leukocytes that were separated with the Ficoll-Paque
      density gradient separation method, then seeded on a previously prepared
      fibroblast layer in Petri dishes. After 7 days, the number and size of bone
      colonies formed in the calcitonin gene related peptide (0.1 or 1 microg/ml) added
      group was significantly greater than that of the control group. There was no
      statistically significant difference between the calcitonin added and control
      groups. Calcitonin gene related peptide has an osteogenic stimulating effect,
      either by stimulating stem cell mitosis or osteoprogenitor cell differentiation
      (or both), whereas salmon calcitonin has no effect.

PMID- 9005932
TI  - Effect of femoral component rotation and patellar design on patellar forces.
AB  - A force transducer attached to the patella was used to measure patellar contact
      forces after total knee arthroplasty for neutral femoral component position and
      for 10 degrees internal and external femoral component rotations. Knees were
      cycled continuously under load from 10 degrees to 110 degrees flexion. Two
      designs of knee replacement with differing degrees of intrinsic tibiofemoral
      constraint were studied. Additionally, contact forces for a dome shaped patella
      and a modified dome shaped patella (a patellar component with a central
      projection surrounded by a peripheral flat region) were compared. When using the
      design with relatively high intrinsic tibiofemoral constraint, there were no
      significant changes in patellar contact forces after axial rotation of the
      femoral component. When using the design with relatively low intrinsic
      tibiofemoral constraint and averaging over the range of flexion angles tested,
      the mediolateral component of the patellar contact force increased approximately
      17% after 10 degrees internal rotation compared with neutral rotation, and the
      normal component of the patellar contact force decreased approximately 8% after a
      10 degrees external rotation compared with 10 degrees internal rotation of the
      femoral component. The inferosuperior component of the patellar shear force, when
      using the modified dome shaped patellar component, was significantly lower than
      for the dome shaped patella.

PMID- 9005933
TI  - Magnetic resonance imaging of the musculoskeletal system. Part 6. The Shoulder.
AB  - The role of magnetic resonance imaging in the diagnosis and treatment of patients
      with shoulder pain has increased remarkably in recent years, largely because of
      improved resolution of images and increased experience of musculoskeletal
      radiologists. In rotator cuff disease/impingement and instability, magnetic
      resonance imaging adds a new dimension to the clinical findings through the
      noninvasive visualization of either the pathology itself or frequently associated
      abnormalities. It is the associated abnormalities that are depicted in
      instability: glenoid irregularities, labral tears, capsular laxity, and Hill
      Sachs deformities. Glenoid, labral, and Hill-Sachs abnormalities can be assessed
      with either magnetic resonance imaging or computed tomography arthrography.
      Magnetic resonance imaging has the advantages of noninvasiveness, multiplanar
      imaging capability and exquisite soft tissue contrast. In rotator cuff disease,
      magnetic resonance imaging depicts the status of the rotator cuff itself,
      revealing partial and full thickness tears, allowing an estimation of size and
      quality of tendon edges. Possible impingement sites can be identified. Primary
      instability with secondary impingement may be first suspected on magnetic
      resonance imaging. Postoperative complications, including recurrent tendon
      detachment, deltoid dehiscence, and infection, are clarified. Unsuspected but
      clinically important lesions, such as neoplasm, osteonecrosis, and ganglion with
      entrapment of the suprascapular nerve, each have characteristic magnetic
      resonance imaging appearances.

PMID- 9005934
TI  - Patron saints of medicine.
AB  - From the earliest times, medical practitioners have sought divine help and
      support to aid them as they go about their busy rounds. In the early Christian
      era, 4 individuals were singled out as patron saints of medicine, and
      particularly of physicians and surgeons. These men were all natives of Asia
      Minor; they were all educated in the Greek medical tradition; and they were all
      busy practitioners. They were the Apostle Luke, Saints Cosmas and Damian and
      Saint Panteleimon. Through the centuries, they have served as worthy role models
      for the physicians who have invoked their aide.

PMID- 9005935
TI  - Enlarging dorsal hand mass in a 64-year-old man.

PMID- 9005936
TI  - Steroid injection technique.

PMID- 9005937
TI  - Effect of pegs and screws on bone ingrowth in cementless total knee arthroplasty.

PMID- 9005938
TI  - Aspirin and warfarin are comparable for prophylaxis.

PMID- 9005939
TI  - Implications for the assay and biological activity of interleukin-8: results of a
      WHO international collaborative study.
AB  - Eight ampouled preparations of interleukin-8 (IL-8) have been evaluated for their
      suitability to serve as an international standard for IL-8 by 30 laboratories in
      12 countries in an international collaborative study. The preparations were
      assayed in a wide range of in vitro bioassays and immunoassays. It is clear from
      the study that different recombinant preparations of IL-8 can have different
      biological specific activities, even though all were produced using E. coli. It
      is of interest that the intra-laboratory variability of estimates provided by
      several neutrophil degranulation bioassays was less than that of the
      immunoassays, suggesting that these bioassays can be as precise, if not more so,
      than immunoassays. In addition, immunoassay estimates of IL-8 preparations
      differed from those of bioassays, illustrating the fact that immunoassays do not
      necessarily measure biologically active cytokine. The large reduction in the
      inter-laboratory variability of estimates in terms of a common reference
      preparation clearly illustrates the need for a standard for IL-8. On the basis of
      the results reported here, with the agreement of the participants of the study
      and with the authorisation of the Expert Committee on Biological Standardization
      (ECBS) of the World Health Organization (WHO) the preparation of IL-8 (89/520)
      was established as the International Standard for IL-8 with an assigned unitage
      of 1000 IU/ampoule.

PMID- 9005940
TI  - A comparison between ELISPOT methods for the detection of cytokine producing
      cells: greater sensitivity and specificity using ELISA plates as compared to
      nitrocellulose membranes.
AB  - We have used the ELISPOT method employing plastic ELISA plates without substrate
      in agar for the detection of single cells producing interferon-gamma (IFN-gamma)
      and interleukin-4 (IL-4). When using PBMC directly stimulated in the assay wells
      with T cell mitogens it was possible to measure production of human IFN-gamma at
      an earlier time point and with a higher sensitivity compared to conventional
      nitrocellulose plates. The plastic surface was not autostimulatory for IFN-gamma
      production, as seems to be the case for nitrocellulose surfaces. Compared to the
      use of nitrocellulose plates, the use of plastic ELISA plates is considerably
      cheaper and easier to perform. The increased sensitivity for cytokine detection,
      together with minimal autostimulatory properties of the detection surface, makes
      this method suitable for the detection of spontaneous low grade cytokine
      production from cells obtained in vivo.

PMID- 9005941
TI  - Interest of immunomodulation as a mean to improve the preparation of polyclonal
      and monoclonal antibody reagents.
AB  - Immunomodulation by monoclonal antibodies (mAbs) was investigated in mice in
      order to improve the preparation of antibody reagents. Three different types of
      representative immunogens were chosen: a human soluble protein (secretory
      immunoglobulin A, SIgA), a bacterial polysaccharide from E. coli K1 and an
      envelope protein from the hepatitis B virus. These Ag are all of importance for
      diagnosis and exhibit different levels of immunogenicity. Antibody-mediated
      enhancement was observed against restricted and defined regions of each immunogen
      i.e.: the Fab epitopes of SIgA, the preS1 domain of the HBV envelope and
      associated cell wall components of the capsular PS. The epitopes which were
      enhanced appeared to be different from those recognized by the modulating mAb.
      Negative modulations were also observed. Moreover, new epitopes seemed to be
      generated. In both cases the level and direction of the modulation were
      irrespective of isotypy and affinity of the mAbs. Interestingly the positive
      modulatory effect was found to be correlated with an in vitro assay based on the
      binding of immune complex to antigen-presenting cells.

PMID- 9005942
TI  - Determination of anti-HBsAg IgM monoclonal antibodies in cell culture media by
      perfusion immunoassay.
AB  - A rapid, specific, perfusion immunoassay for active anti-HBsAg monoclonal IgM is
      described. The immunoassay requires less than 3.5 min per sample. The precision
      was found to be 3.6% at an IgM concentration of 17 microg/ml. A detection limit
      of 1 microg/ml IgM in culture media was determined. Assay results were found to
      correlate very well with standard size exclusion chromatography and radial
      immunodiffusion techniques. This perfusion immunoassay was demonstrated to be
      useful for determining anti-HBsAg IgM in complex matrices such as cell culture
      media. The utility of the immunoassay for monitoring production of anti-HBsAg IgM
      in a perfusion bioreactor is demonstrated.

PMID- 9005943
TI  - Inhibition of tumor growth by peptide specific cytotoxic T lymphocytes in a three
      dimensional collagen matrix.
AB  - Tumor associated, MHC I restricted antigenic peptides have been identified in
      both human and mouse tumors. Cytotoxic T lymphocytes (CTL) which recognize these
      tumor associated antigenic peptides are potential anti-cancer effectors. The anti
      tumor activity of CTL is usually measured in vitro by the 51Cr release assay and
      in mice by tumor growth inhibition which is the most direct assessment of anti
      tumor effect. In clinical studies, an in vivo tumor growth inhibition assay is
      not an option and an in vitro assay which corroborates with in vivo tumor growth
      is needed to assess the long-term outcome of CTL activity. Here, a three
      dimensional (3-D) collagen gel assay was developed to measure in vitro the
      inhibition of mouse mammary tumor growth by anti-tumor CTL. BALB/c mouse CTL were
      induced with peptide E474 SFAVATTAL which was expressed by mouse mammary tumor
      cells D2F2. To measure D2F2 tumor growth inhibition in vitro, a mixture of tumor
      cells and anti-E474 CTL in a 1 microl cell bolus was embedded in the collagen
      gel. Complete eradication of tumor growth was observed at E:T ratio of or greater
      than 1:1. rIL-2 supplementation was necessary to achieve long-term tumor growth
      inhibition. Even spontaneous D2 tumor explant could be grown in the collagen gel
      and addition of anti-E474 to this culture reduced tumor growth. This assay system
      provides a realistic and sensitive alternative to the in vivo tumor growth
      inhibition assay and allows easy adaptation to test additional therapeutic
      reagents.

PMID- 9005944
TI  - Functional assays for evaluation of serogroup B meningococcal structures as
      mediators of human opsonophagocytosis.
AB  - Functional flow cytometry and chemiluminescence (CL) assays have been modified to
      identify serogroup B meningococcal structures that mediate anti-meningococcal
      opsonophagocytosis. Serogroup B meningococcal outer membrane vesicles (OMV) were
      adsorbed to fluorescent latex beads (OMV-beads) and opsonized with acute phase
      and convalescence sera from patients with serogroup B meningococcal disease.
      Phagocytosis of these beads by human monocytes and polymorphonuclear leukocytes
      (non-lymphocytes) was dependent on both antigen exposure on the bead surface and
      on serum opsonization. OMV-beads opsonized with serum from a patient recovering
      from meningococcal disease, caused 97% of the non-lymphocytes to phagocytose an
      average of 15.8 beads per cell with a CL response of 46,550 mVs, whereas
      opsonized control beads were phagocytosed by 19% of the non-lymphocytes with 1.1
      beads per cell and a CL response of 53 mVs. Increased amounts of functional, anti
      OMV opsonins were detected during infection, and opsonized OMV-beads elicited
      phagocyte responses of similar magnitude to those of opsonized whole
      meningococci. Phagocyte internalization of OMV-beads was confirmed by confocal
      laser scanning microscopy. We conclude that epitopes on the meningococcal outer
      membrane are recognized by anti-meningococcal opsonins in these functional
      phagocytosis assays, which provide a basis for subsequent evaluation of various
      purified bacterial components as mediators of human opsonophagocytic responses
      and hence future vaccine constituents.

PMID- 9005945
TI  - High level production of soluble single chain antibodies in small-scale
      Escherichia coli cultures.
AB  - We have investigated the effect of growth and induction conditions on the
      production of soluble single-chain Fv antibody fragments in Escherichia coli
      under the control of wt lac promoter. The scFv was directed into the periplasmic
      space by a pelB leader sequence. Addition of sucrose to the medium gave a 15-25
      fold increase in the yield of soluble scFv-phOx (3.0 mg/l) for bacterial shake
      tube cultures and an increase of 80-150-fold (16.5 mg/l) for shake-flask
      cultures. Using flask culture in the presence of 0.4 M sucrose, a significant
      amount of scFv was released into the medium. We found that the scFv could be made
      to accumulate in the periplasm or be secreted into the medium by simply changing
      the incubation conditions and the concentration of the inducer. The ratio between
      soluble antibody fragments and insoluble scFv aggregates proved to be dependent
      on the strength of the promoter. Lowering the incubation temperature below 20
      degrees C had no effect on the yield of soluble antibody fragments in the
      periplasm, but they were no longer secreted into the medium. An example of high
      level production in shake-flask cultures and one-step purification by immobilized
      metal affinity chromatography (IMAC) is described for a soluble scFv specific for
      the T cell surface antigen CD3. The biological activity of the purified anti-CD3
      scFv was demonstrated by flow cytometry. This method should be especially useful
      for the functional screening of a large number of clones in small-scale cultures.

PMID- 9005946
TI  - Optimisation of a peptide-based indirect ELISA for the detection of antibody in
      the serum of HIV-1 seropositive patients.
AB  - A modified peptide-based indirect ELISA technique for the detection of HIV-1
      specific antibodies in the sera of HIV-1 seropositive individuals is described.
      We found that the reduction of non-specific binding of HIV-1 seropositive sera to
      the ELISA plate was essential for the reliable detection of serum antibodies in
      the peptide based indirect ELISA. Optimal results were obtained using Immulon
      microtitre plates, different concentrations of denatured. purified grade of
      casein in the blocking (1%) and washing (0.25%) solutions and by diluting HIV-1
      seropositive sera 1 in 1600. These conditions reduced non-specific binding and
      improved assay sensitivity. We show that the inclusion of a control peptide is
      essential to reducing the incidence of false positive and false negative results.
      Taken together, the modifications described in this report improve reliability of
      the peptide-based indirect ELISA without compromising its sensitivity and have
      particular relevance for those wishing to apply the peptide-based indirect ELISA
      technique to serum samples which exhibit high levels of non-specific binding. To
      illustrate this, levels of antibody in the sera of HIV-1 seropositive and
      seronegative donors that are specific for peptides derived from a conserved
      region of HIV-1 gp120 sharing homology with the FAS apoptosis antigen were
      analysed using this technique.

PMID- 9005947
TI  - A sensitive fluorometric assay for quantitatively measuring specific peptide
      binding to HLA class I and class II molecules.
AB  - A sensitive, highly reproducible assay was developed for measuring binding of
      peptides to various HLA class I and II alleles. The assay is based on competition
      for binding to HLA between a peptide of interest and a fluorescent labelled
      standard peptide. This mixture is incubated with HLA to obtain equilibrium
      binding, and subsequently separated on an HPLC size-exclusion column in (i) a
      protein fraction containing HLA and bound peptide and (ii) a free peptide
      fraction. Each assay uses only 100 fmol labelled peptide and approximately 10
      pmol of HLA. The analytical system contains an autosampler that samples from 96
      well microtiter plates. Injections and data recording/evaluation is fully
      automated. Typical analysis time is 10-12 min per sample. The fluorescence in the
      HLA-bound peptide and free peptide containing fractions is measured on-line. The
      ratios of fluorescence signal in protein and peptide fractions at various
      concentrations of the peptide of interest are determined. IC50 values are
      calculated from the binding curve as obtained by curve fitting of the data. Here
      we show results for peptide binding to HLA-DR1 and -DR17 molecules purified from
      detergent solubilized cell lysates. and for recombinant HLA-A*0201 and HLA-A*0301
      expressed in E. coli. The assay reported is sensitive and reproducible. It is non
      radioactive and is non-labor intensive due to the high degree of automation.

PMID- 9005948
TI  - A non-denaturing enzyme linked immunosorbent assay with protein preadsorbed onto
      aluminum hydroxide.
AB  - A method has been developed which prevents denaturation of proteins used for
      coating of plastic surfaces in enzyme linked immunosorbent assays (ELISA). The
      system takes advantage of the use of aluminum hydroxide (Al(OH)3) as an adsorbent
      for proteins. A model protein has been analyzed. and monoclonal antibodies
      specific for either the native form or the denatured form of the protein were
      used to monitor the extent of denaturation. Adsorption of the proteins to Al(OH)3
      in carbonate buffer, pH 9.3, before coating the ELISA plate abolished the
      denaturation otherwise observed after direct adsorption of protein to plastic
      surfaces. The protection against denaturation was dependent on the buffer system
      and was not observed when phosphate buffers were used, due to elution of protein
      from Al(OH)3 or lack of binding to Al(OH)3 in the presence of phosphate. There is
      evidence that protein adsorbed onto the Al(OH)3 is required for binding of
      Al(OH)3 onto the plastic surface. This system may be useful in assay systems
      where discrimination between the native and denatured forms of proteins is
      important.

PMID- 9005949
TI  - In vitro separation and expansion of CD4 lymphocytes from HIV-infected
      individuals without activation of HIV infection.
AB  - In order to offer a gene therapy-based treatment against AIDS, it is likely to be
      necessary to harvest and culture CD4 cells from HIV-positive patients without
      activating the HIV infection. We have used a magnetic cell sorting (MACS) system
      to enrich CD4 cells. Using positive selection, CD4 cells from a total of 14
      patients were enriched from a mean percentage of CD4 cells in PBMC of 18% to 91%
      CD4 cells in the enriched cell fraction. Furthermore, we found that this
      separation did not lead to an increase in viral load. The MACS performed equally
      well on cells from HIV-positive patients and HIV-negative donors. CD4 cells from
      HIV-positive patients were readily expanded with PHA; 19-fold by day 10, 50-fold
      by day 20, and 156-fold by day 25. However, CD4 cells from HIV-positive patients
      grew at a slower rate than CD4 cells from HIV-negative donors. The expanded CD4
      cells showed a high degree of CD4 expression and no loss of polyclonality. Only
      in two of six cultures were we able to detect HIV-antigen production, and using
      an LTR-PCR and an RT assay, we did not find activation of the HIV infection
      during the culture period. Thus, the method described separates and expands CD4
      cells from HIV-positive patients without activation of the HIV infection.

PMID- 9005950
TI  - vWf inhibitor detection by competitive ELISA.
AB  - An inhibitor to von Willebrand factor (vWf) was detected in the plasma from two
      patients with histories of mild bleeding and one patient with a severe deficiency
      in the Factor VIII complex using a competitive enzyme-linked immunosorbent assay
      (ELISA) procedure. IgG antibodies from the patients' plasmas were shown to bind
      to vWf immobilised on polystyrene beads by flow cytometry. The inhibitor also
      potentiated a recently described platelet function assay based on stirring vWf
      immobilised on polystyrene beads with platelet rich plasma (PRP). Upon addition
      of mAb IV.3, potentiation of vWf bead-induced platelet activation was lost
      indicating that the enhancement of platelet activation was Fc receptor-dependent.
      Since the ELISA described can be used to quantitate vWf and to detect inhibitors
      to vWf in plasma samples, the method should prove useful in differentiating
      acquired vWd from congenital vWd.

PMID- 9005951
TI  - Experimental design for kinetic analysis of protein-protein interactions with
      surface plasmon resonance biosensors.
AB  - The reaction between antibody immobilized to surfaces, with and without a dextran
      matrix, and antigen in solution was studied using surface plasmon resonance
      detection. The use of a reference surface made it possible to identify conditions
      where a response related to changes in matrix conformation could be ignored. It
      was possible therefore to improve data quality by separating signals related to
      binding events from signals due to differences in refractive index between sample
      and running buffer. When antigen was injected over antibody immobilized to
      surfaces with and without dextran matrix the binding curves were virtually
      superimposable. Consequently, no binding artifacts associated with the dextran
      matrix were observed. Sets of binding curves obtained with different antigen
      concentrations were analyzed using numerical integration of differential rate
      equations and global fitting. When data was inconsistent with a one to one
      reaction it was possible to obtain good fits to an entire data set assuming
      several other reaction schemes including parallel, competitive and two-state
      reactions. Thus data analysis alone was not sufficient to discriminate between
      different reaction schemes. In contrast several reaction schemes could be ruled
      out with simple experiments; the duration of antigen injection, and reanalysis of
      antigen recovered in fractions from the antibody surface. In view of these
      findings experimental design appears to be the key to successful interaction
      analysis.

PMID- 9005952
TI  - Modulation of P-selectin expression on isolated human platelets by an NO donor
      assessed by a novel ELISA application.
AB  - Adhesion molecules such as P-selectin are potential markers for evaluating
      platelet activation and studying the role of cell-cell interactions in numerous
      biological processes related to hemostasis and inflammation. The expression of P
      selectin and related molecules has previously been quantified with different
      techniques. As an alternative to the most common method. flow cytometry, we have
      developed a useful ELISA method to simultaneously analyse 96 samples for platelet
      expression of P-selectin. Samples may be stored for at least 7 days at 4 degrees
      C prior to analysis. The method is simple, reproducible, flexible and requires
      only standard equipment. Washed platelets (WP) from healthy male volunteers, at a
      concentration of 1 x 10(7)/microtiter plate well, were stimulated with various
      known platelet activators and fixed with 0.1% formaldehyde for 10 min. The fixed
      WP were centrifuged to form a confluent layer in the wells and then incubated
      with optimal dilutions of primary antibodies (1/2000) directed against P
      selectin, CD41, CD9 and secondary antibodies conjugated with alkaline
      phosphatase. Our results show that P-selectin expression on WP increases
      significantly upon stimulation with thrombin (0.1-1.0 U/ml), ADP (10 microM) and
      epinephrine (100 microM). The induction of P-selectin expression by thrombin is
      fast and has different kinetics depending on the concentration of the agonist.
      Prior incubation with the nitric oxide donor SNAP (10 microM) inhibits the up
      regulation of P-selectin induced by sub-maximal concentrations of thrombin (p <
      0.05). This ELISA is suitable for studying the expression and regulation of P
      selectin and other surface molecules on human platelets in various pathological
      states.

PMID- 9005953
TI  - Competitive flow injection enzyme immunoassay for steroids using a post-column
      reaction technique.
AB  - Two types of flexible, sensitive and rapid competitive flow injection enzyme
      immunoassay were developed and evaluated for their potential use in the
      bioanalysis of steroids. Instead of the more typical approach where the signal is
      generated from antibody-bound hapten-enzyme conjugate, the non-bound fraction
      passing through the affinity column was allowed to react with an enzyme substrate
      from a merging channel in a post-column reaction system. The enzyme product (p
      aminophenol or 4-methyl umbelliferol) was amperometrically or fluorometrically
      detected. Several parameters known to affect signal generation in the immunoassay
      were evaluated, including flow rate through the affinity column and through the
      reaction coil, the length of the reaction coil and of the affinity column. In the
      pre-incubation approach, where samples were mixed with enzyme conjugate and
      antibodies before injection, a sample throughput as high as 20 h(-1) was
      possible. The signal precision was about 1% (RSD) for cortisol (0.6-80 pmol) and
      2% (RSD) for budesonide (0.02-12.5 pmol). In the displacement assay for cortisol,
      enzyme-labelled analyte was displaced from the affinity column when the sample
      was injected into the flow. A standard curve was obtained with a signal precision
      of 4-20% for 12.5-1250 pmol injected. The same instrumental set-up was used in
      both types of immunoassay, and thus a highly flexible system was obtained. A
      simple replacement of the affinity column from protein G in the pre-incubation
      approach to a column containing primary antibodies in the displacement assay was
      needed.

PMID- 9005954
TI  - Measurement of antibody/antigen association rate constants in solution by a
      method based on the enzyme-linked immunosorbent assay.
AB  - A reliable ELISA based method has been developed for measuring in solution
      antigen/antibody association rate constants. Its rationale is as follows: antigen
      and antibody are mixed in solution to initiate the association. At different time
      intervals aliquots are withdrawn to determine by an indirect ELISA the amount of
      free antibody that remains in solution. The disappearance of the free mAb
      reflects the time course of the association reaction. To test the validity of
      this method, the association rate constant of a monoclonal antibody for its
      antigen was measured and compared with that obtained previously by a method using
      fluorescence. The good agreement between the results obtained with the ELISA
      based method and those obtained previously by fluorescence measurement indicates
      that the method described permits determination of true association rate
      constants in solution. The present method offers several advantages. It uses only
      minute amounts of sample which need not be purified; it requires no radioactive
      or fluorescent labelling of the antibody or the antigen, and it can be applied to
      any type of complex between macromolecules if an ELISA test can be set up to
      detect quantitatively one of the macromolecules.

PMID- 9005955
TI  - A novel method for the production of antibodies against ACTH: their
      characterization and use in epitope mapping.
AB  - Our earlier attempts at immunization with human adrenocorticotropin hormone
      (ACTH) were unsuccessful and we therefore developed a new strategy including the
      chemical modification of the hormone by succinic anhydride in order to increase
      its immunogenicity. This process allowed us to obtain antisera with titers of up
      to 1/1000 and yielded 39 anti-succinylated ACTH (sACTH)-secreting hybridomas.
      Subsequently, the epitopes of sACTH were mapped by testing monoclonal antibodies
      two by two for simultaneous binding to sACTH and for their capacity to recognize
      its succinylated fragments 1-13, 1-17 and 1-24. The results, obtained with the
      use of radioactive tracers, were confirmed by and complemented with experiments
      conducted with biosensor technology. Seven groups of antibodies were defined on
      the basis of their pattern of reactivity and it was shown that four monoclonal
      antibodies could bind simultaneously to sACTH. Their dissociation constants (Kd)
      for sACTH were calculated and ranged from 10(-8) M to 10(-11) M. In order to
      obtain a fast and sensitive immunoassay for the hormone, we developed a protocol
      for the chemical modification of ACTH in serum and the most efficient monoclonal
      antibodies were selected on the basis of the epitope map and of their
      dissociation constants.

PMID- 9005956
TI  - The function of neutrophils isolated by a magnetic antibody cell separation
      technique is not altered in comparison to a density gradient centrifugation
      method.
AB  - Most comparative studies on neutrophil (PMN) isolation techniques have shown
      either activation or functional impairment of the cells due to the different
      separation processes. We have established a preparation method for PMN from human
      whole blood employing iron tagged, magnetizable antibodies against the cell
      surface antigen CD15. The aim of our study was to test whether this magnetic
      separation (MACS) alters cellular functions of PMN in comparison to a
      conventional density gradient technique (Percoll). The purity, cell yield, and
      pre-activation of the cells were evaluated. The latter was assessed by
      quantifying the expression of the integrin CD11b using flow cytometry.
      Furthermore, as functional tests, cell morphology and the oxidative burst
      reaction were investigated. We have shown that the use of 'magnetic' antibodies
      leads to highly purified PMN (> 99% of isolated leukocytes), while there is still
      contamination by eosinophils (about 6%) after Percoll separation. Platelet
      contamination was about the same in both procedures (approx. one platelet per two
      PMN). The basal expression of CD11b and, hence, neutrophil activation, was
      significantly lower and the upregulation of CD11b in response to FMLP was more
      pronounced after magnetic separation, as compared to density gradient
      centrifugation. The MACS technique did not lead to polarisation of PMN, nor did
      it affect the oxidative burst. This study suggests that magnetic separation is a
      simple, time-saving technique, yielding highly purified and functionally intact
      PMN.

PMID- 9005957
TI  - Induction of antigen-specific isotype switching by in vitro immunization of human
      naive B lymphocytes.
AB  - The use of in vitro immunization technology for the generation of human antigen
      specific antibodies has essentially resulted in low affinity IgM antibodies,
      resembling an in vivo primary immune response. We now describe a detailed
      reproducible protocol for a two-step in vitro immunization, which yields isotype
      switched, antigen-specific human antibodies. The immunizing antigen was a 30aa
      synthetic peptide, containing both a B (15aa V3 peptide of the HIV-1) and a T
      helper cell epitope (15aa peptide from tetanus toxin). The immunization protocol
      includes: (i) a selection procedure of donors with a memory T cell response
      against tetanus toxoid; (ii) immunization of mature naive peripheral B
      lymphocytes in two distinct phases, involving a primary and a secondary step.
      None of the donors which were examined after primary immunization showed at any
      time an IgG anti-V3 specific antibody response, while all the donors showed an
      IgM response. After the secondary immunization step, anti-V3 antibodies of both
      IgM and IgG isotypes were detected. The switch frequency event was high among the
      tested donors (5/8).

PMID- 9005959
TI  - Corrections to the original lactate dehydrogenase (LDH) release assay for the
      evaluation of NK cell cytotoxicity.

PMID- 9005958
TI  - Induction of antigen-presenting capacity in tumor cells upon infection with non
      replicating recombinant vaccinia virus encoding murine MHC class II and
      costimulatory molecules.
AB  - The possibility of inducing antigen-presenting capacity in cells normally lacking
      such capacity, currently represents a major goal in vaccine research. To address
      this issue we attempted to generate 'artificial' APC able to stimulate CD4+ T
      cell responses when tumor cells were infected with a single, recombinant,
      vaccinia virus (rVV) containing the two genes encoding murine MHC class II I-Ak
      and a third gene encoding the murine B7-1 (mB7-1) costimulatory molecule. To
      minimize the cytopathic effect and to improve safety, in view of possible in vivo
      applications, we made this rVV replication incompetent by Psoralen and long wave
      UV treatment. Tumor cells infected with rVV encoding I-Ak alone, pulsed with hen
      egg white lysozyme peptide (HEL46-61), induced IL-2 secretion by an antigen
      specific T hybridoma. Tumor cells infected with the rVV encoding mB7-1 provided
      costimulation for activating resting CD4+ T cells in the presence of ConA. Tumor
      cells infected with the rVV encoding I-Ak and mB7-1, and pulsed with chicken
      ovotransferrin peptide (conalbumin133-145), induced a significantly higher
      response in a specific Th2 cell clone (D10.G4.1) as compared to cells infected
      with rVV encoding I-Ak molecules only. Thus, this replication incompetent rVV
      represents a safe, multiple gene, vector system able to confer in one single
      infection step effective APC capacity to non-professional APCs.

PMID- 9005960
TI  - Ketosis resistance in fibrocalculous pancreatic diabetes: II. Hepatic ketogenesis
      after oral medium-chain triglycerides.
AB  - A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not
      become ketotic even in adverse conditions. It is not clear whether this ketosis
      resistance is due to reduced fatty acid release from adipose tissue or to
      impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients
      using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and
      compared it with that in matched insulin-dependent diabetes mellitus (IDDM)
      patients and healthy controls. After oral MCTs, FCPD patients showed only a mild
      increase in blood 3-hydroxybutyrate (3-HB) concentrations (median: fasting, 0.13
      mmol/L; peak, 0.52) compared with IDDM patients (fasting, 0.44; peak, 3.39) and
      controls (fasting, 0.04; peak, 0.75). Plasma nonesterified fatty acid (NEFA)
      concentrations were comparable in the two diabetic groups (FCPD: fasting, 0.50
      mmol/L; peak, 0.79; IDDM: fasting, 0.91; peak, 1.04). Plasma C-peptide
      concentrations were low and comparable in the two diabetic groups. Plasma
      glucagon concentrations were higher in IDDM patients in the fasting state, but
      declined to levels comparable to those in FCPD patients after oral MCTs. Plasma
      carnitine concentrations were comparable in the two groups of patients. It is
      concluded that the failure to stimulate ketogenesis under these conditions could
      be partly due to inhibition of a step beyond fatty acid entry into the
      mitochondria.

PMID- 9005961
TI  - Determinants of sex hormone-binding globulin blood concentrations in
      premenopausal and postmenopausal women with different estrogen status. Virgilio
      Menopause-Health Group.
AB  - In women, sex hormone-binding globulin (SHBG) concentrations are the result of a
      balanced effect of stimulatory and inhibitory factors. Estrogens represent the
      principal stimulatory hormones, whereas androgens, insulin, excess body fat, and
      the pattern of body fat distribution have inhibitory effects. Menopause is
      characterized by major changes in blood sex steroid concentrations, notably a
      marked reduction of estradiol levels. In this study, we therefore investigated
      the relationship between hormonal and nonhormonal regulatory factors of SHBG and
      its blood levels in two groups of premenopausal and postmenopausal women
      characterized by normal-high or reduced estrogen concentrations. The data were
      obtained from an analysis of the cross-sectional database obtained during the
      first survey of the Virgilio-Menopause-Health Project, an epidemiologic
      longitudinal study aimed at investigating the impact of menopause on body weight,
      fat distribution, and related major metabolic, hormonal, and cardiovascular risk
      factors. A total of 329 women, 133 in premenopause and 196 in postmenopause
      without diabetes, thyroid diseases, or relevant cardiovascular, renal, and
      hepatic dysfunction, were included in the study. A clinical history (including
      dietary and physical-activity habits), anthropometry (body mass index [BMI],
      waist to hip ratio [WHR], and bioelectrical impedance analysis [BIA]), and
      morning blood samples in the fasting state for sex hormones, insulin, and
      biochemistry were available for all the women. Premenopausal and postmenopausal
      women showed no significant difference in SHBG concentrations (38.7 +/- 17.9 v
      36.6 +/- 17.5 nmol/L, respectively). On the contrary, postmenopausal women were
      characterized by a marked reduction of estradiol levels and significantly lower
      levels of testosterone. After adjusting for age, insulin was lower and the
      glucose to insulin ratio was higher in postmenopause than in premenopause. Age
      adjusted values for all anthropometric parameters were not significantly
      different in the two groups. In simple correlation models, SHBG was significantly
      and negatively correlated with BMI, WHR, and insulin and testosterone levels in
      both premenopausal and postmenopausal women, whereas estradiol levels correlated
      positively and significantly with SHBG only in the premenopausal group. A
      significant positive correlation between the glucose to insulin ratio and SHBG
      was present in both groups. Using multiple regression models, in the
      premenopausal group, SHBG levels were correlated positively with estradiol and
      negatively with testosterone and insulin, but not with the WHR. On the contrary,
      in the postmenopausal group, SHBG values had a significant negative correlation
      with the WHR, whereas the relationship with estradiol was not significant;
      moreover, the relationship with testosterone and insulin, although significant,
      became less marked. In conclusion, this study indicates that (1) there is no
      significant difference in SHBG blood concentrations between premenopause and
      postmenopause; (2) SHBG values are correlated positively with estradiol and
      negatively with insulin and testosterone concentrations, but the predictive value
      of these variabiles on SHBG appears to be different in premenopause and
      postmenopause; and (3) SHBG levels decrease with increasing WHRs, particularly in
      the postmenopausal group. Therefore, determinants of SHBG blood concentrations
      are likely to change on passing from premenopausal to postmenopausal status. In
      particular, there seems to be a threshold level for which estradiol is an
      important determinant of SHBG blood concentrations.

PMID- 9005962
TI  - Unususal increase of lipogenesis in rat white adipose tissue after multiple
      cycles of starvation-refeeding.
AB  - The purpose of the study was to determine the response of liver and brown (BAT)
      and white (WAT) adipose tissue lipogenesis and total body weight in rats
      subjected to multiple cycles of 3 days of fasting and 3 days of refeeding. Rats
      fasted for 3 days showed significant reduction in body weight. These changes were
      reversed on 3 days' refeeding. Body weight was much higher in rats fed ad libitum
      than in animals experiencing more than one cycle of 3 days of fasting followed by
      3 days of refeeding. Despite the significant body weight reduction, an unusual
      increase of lipogenesis in WAT was found after multiple cycles of starvation
      refeeding of rats on standard laboratory diet. The rate of lipogenesis in the
      liver and BAT was also elevated but to a much smaller extent. A parallel increase
      in enzymatic activities related to fatty acid synthesis, ie, fatty acid synthase,
      acetyl-coenzyme A carboxylase, adenosine triphosphate (ATP)-citrate lyase, NADP
      linked malic enzyme, and hexose monophosphate shunt dehydrogenases, suggests that
      the increased rate of lipogenesis in WAT is a consequence of increased lipogenic
      enzyme activities. These data suggest that upregulation of WAT lipogenesis occurs
      after the multiple cycles of the starvation-refeeding protocol. An unusual
      increase of lipogenesis in rat WAT may have a survival advantage, because starved
      refed rats must develop the ability to ingest large amounts of food during a
      refeeding period to store it in a convenient form than can be used as an
      oxidizable substrate during a period of starvation. Moreover, these results
      suggest that it is possible to develop appropriate starvation-refeeding
      conditions that may inhibit body weight gain.

PMID- 9005963
TI  - Brain beta-adrenergic receptor binding in rats with obesity induced by a beef
      tallow diet.
AB  - We have previously reported that compared with safflower oil diet, feeding a beef
      tallow diet leads to a greater accumulation of body fat by reducing sympathetic
      activities. The present study examined the effects of dietary fats consisting of
      different fatty acids on alpha1- and beta-adrenergic receptor binding in the
      hypothalamus and cerebral cortex. Male Sprague-Dawley rats were meal-fed
      isoenergetic diets based on safflower oil (rich in n-6 polyunsaturated fatty
      acids) or beef tallow (rich in saturated fatty acids) for 8 weeks. Binding
      affinities of the beta-adrenergic receptor in the hypothalamus and cortex were
      significantly lower in the beef tallow diet group, but those of the alpha1
      receptor did not differ between the two groups. The polyunsaturated to saturated
      fatty acid (P/S) ratio and fluidities of plasma membranes in the hypothalamus and
      cortex were lower in the beef tallow diet group than in the safflower oil diet
      group. These results suggest that the beef tallow diet decreases membrane
      fluidity by altering the fatty acid composition of plasma membranes in the
      hypothalamus and cerebral cortex of rat. Consequently, beta-adrenergic receptor
      binding affinities in the brain were lower in rats fed the beef tallow diet than
      in rats fed the safflower oil diet. We recognized that there is possible link
      between the membrane fluidity and the changes in affinity of beta-adrenoceptors
      in rat brain.

PMID- 9005964
TI  - Growth hormone modulates amino acid oxidation in the surgical patient: leucine
      kinetics during the fasted and fed state using moderate nitrogenous and caloric
      diet and recombinant human growth hormone.
AB  - Twelve patients (aged 70 +/- 9 years) who were scheduled for resection of
      rectosigmoid colon adenocarcinoma but were otherwise healthy were randomly
      allocated after surgery to receive either peripheral parenteral nutrition alone
      ([PPN] n = 6) or in combination with recombinant human growth hormone (rGH) at a
      daily dose of 0.15 U x kg(-1) x d(-1)(PPN + rGH, n = 6). The daily nutritional
      regimen was 0.1 g nitrogen x kg(-1) x d(-1) and 20 kcal x kg(-1) x d(-1)
      (nonprotein energy was supplied as 60% lipid and 40% carbohydrate), and it was
      maintained for 6 days before and 6 days after surgery. Protein kinetics were
      studied in all 12 patients during the fasted and fed states before and 6 days
      after surgery using an 8-hour 13C-leucine tracer infusion. Daily urinary
      nitrogen, gaseous exchange, and plasma insulin, growth hormone, and insulin-like
      growth factor-I (IGF-I) were determined before and after surgery. Surgery was
      responsible for significant increases in postabsorptive whole-body protein flux
      and synthesis and leucine oxidation (P < .01). Supplementation of PPN with rGH
      contributed to a significant attenuation of the postoperative increase in leucine
      oxidation (P = .02), with a significant increase in whole-body protein synthesis
      (P = .02) and no effect on protein breakdown (P = .40). During the fed state,
      leucine oxidation increased significantly (P = .005), with the greatest change
      occurring in the PPN group. Feeding was associated with a significant decrease in
      whole-body protein breakdown before and after surgery in both groups (P = .001).
      Postoperative urinary nitrogen excretion was lower but was not statistically
      significant in the PPN + rGH group compared with the PPN group. There was a
      significant increase in oxygen consumption (VO2) and carbon dioxide production
      (VCO2) as a result of feeding and surgery (P < .01). Supplementation with rGH
      caused a decrease in the respiratory quotient (RQ) (P = .04), particularly after
      surgery, indicating a direct effect of rGH on fatty acid oxidation. Circulating
      plasma insulin increased significantly in both groups with feeding and rGH
      supplementation (P < .05). This was enhanced after surgery, particularly in the
      rGH group (P < .05). Plasma growth hormone decreased after surgery in the PPN
      group (P < .05), but did not change as a result of feeding. The circulating
      levels increased in the PPN + rGH group following subcutaneous administration
      before or after surgery. Plasma IGF-I decreased after surgery in the PPN group (P
      < .05), and no changes occurred in the PPN + rGH group with feeding. The present
      findings suggest a distinct positive effect of rGH on protein synthesis in
      catabolic patients receiving a moderate intake of nitrogen and calories. This is
      achieved by modulation of amino acid oxidation. The acute effect of intravenous
      (IV) nutrients on protein metabolism during the catabolic phase of surgical
      stress caused a direct decrease in protein breakdown with no effect on protein
      synthesis.

PMID- 9005965
TI  - Effect of graded renal ablation on kidney and serum insulin-like growth factor-I
      (IGF-I) and IGF binding proteins in rats: relation to compensatory renal growth.
AB  - Kidney insulin-like growth factor-I (IGF-I) increases transiently following
      unilateral nephrectomy, thus preceding the compensatory renal growth. The aim of
      the present study was to investigate the effect of different degrees (1/7 to 2/3)
      of renal ablation on kidney and serum IGF-I and IGF binding proteins (IGFBPs)
      during a 7-day study period. All nephrectomized rats exhibited an increase in the
      weight of the remaining renal tissue. Kidney IGF-I measured in kidney pieces
      close to and away from the resected area increased transiently and more
      significantly away from the resected area, with significant correlation to the
      amount of tissue resected (day 1, r = .73, P < .0001; day 2, r = .49, P < .05;
      and day 7, r = .48, P < .05). No changes in kidney IGFBPs or serum IGF-I were
      observed. Serum IGFBP-4 correlated to the degree of renal resection, as did
      changes in serum urea and creatinine. In conclusion, significant correlations
      were observed between local changes in kidney IGF-I and serum IGFBP-4 levels and
      the degree of renal ablation, suggesting a role for IGF-I as a renotropic factor
      and, further, that IGFBP-4 is removed to a major extent through the kidney.

PMID- 9005966
TI  - Plasminogen activator inhibitor-1 activity in chronic renal disease and dialysis.
AB  - The activity of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of
      fibrinolysis, is associated with insulin resistance (IR) and the risk of venous
      and arterial thrombotic cardiovascular disease (CVD) in the general population,
      and may behave as an acute-phase reactant. PAI-1 activity was measured in 124
      patients with chronic renal disease, and its relationship with alterations in
      metabolic, lipid, and cytokine parameters and the prevalence of CVD complications
      was explored. Patients with chronic renal disease not requiring dialysis were
      divided into a low proteinuric ([LP]n = 30) or high proteinuric ([HP]n = 31)
      group and compared with patients on continuous ambulatory peritoneal dialysis
      ([CAPD]n = 32) or hemodialysis([HD]n = 31) and with 31 healthy controls. Patients
      on HD had significantly lower PAI-1 activity than HP, CAPD, and control groups,
      but no group had significantly higher values than the controls (AU/mL: 7.4 +/-
      3.8 HD, 11.2 +/- 8.4 CAPD, 9.4 +/- 5.4 LP, 12.1 +/- 8.0 HP, 11.4 +/- 6.6
      controls, P = .04). Interleukin-6 (IL-6), the mediator of the acute-phase
      response, was determined in a subset of patients and was significantly increased
      in HD, CAPD, and LP groups compared with the controls (median, pg/mL: 4.6 HD, 4.0
      CAPD, 2.9 LP, 2.4 HP, and 1.5 controls, P < .001), but did not correlate with PAI
      1. PAI-1 independently correlated with body mass index (BMI), triglycerides, and
      lipoprotein(a) [Lp(a)] in stepwise regression for all patients. Dividing the
      whole patient group by tertiles of triglycerides and BMI, increased PAI-1 was
      confined to the subgroup of patients with both obesity (BMI > 26.7 kg/m2) and
      hypertriglyceridemia (triglycerides > 2.5 mmol/L). These data suggest that PAI-1
      activity in chronic renal disease and dialysis was more strongly associated with
      the common metabolic abnormalities of obesity and hypertriglyceridemia than with
      renal disease status, dialysis, or a chronic inflammatory state. This study does
      not support but does not exclude a major role for increased PAI-1 activity in CVD
      risk in chronic renal disease.

PMID- 9005967
TI  - Effect of inhibition of aldose reductase on glucose flux, diacylglycerol
      formation, protein kinase C, and phospholipase A2 activation.
AB  - Activation of the polyol pathway under hyperglycemic conditions is proposed to
      contribute to the development of diabetic nephropathy. The mechanisms by which
      this activation may lead to functional and structural changes within the kidney
      are yet to be definitively established. We have examined in vitro the steps
      linking increased polyol pathway activity resulting from hyperglycemia to
      prostaglandin production. Following the demonstration of increased prostaglandin
      E (PGE) levels in glomeruli from diabetic rats (14.9 +/- 2.5 v 59.1 +/- 19.4 ng
      PGE/mg protein), a specific inhibitor of aldose reductase, HOE-843, was used in
      vitro to analyze the response to hyperglycemia of the steps preceding
      prostaglandin production. In explants of glomeruli from control animals,
      increasing the glucose concentration in vitro from 5.6 mmol/L to 25 mmol/L
      resulted in a significant increase in the flux of glucose through the pentose
      phosphate pathway ([PPP] 1.29 +/- 0.08 v 2.00 +/- 0.11 nmol/h), de novo
      diacylglycerol synthesis (2.2 +/- 0.1 v 3.1 +/- 0.2 micromol/mg protein),
      membrane protein kinase C (PKC) activity (18.7 +/- 0.5 v 24.3 +/- 0.75
      pmol/microg protein), and in vitro phospholipase A2 (PLA2) activity (2.18 +/-
      0.46 v 3.83 +/- 1.07 nmol arachidonic acid hydrolyzed/min/mg cytosolic protein).
      For all parameters measured, the increase resulting from the increased glucose
      concentration could be prevented by in vitro addition of HOE-843 for 24 hours
      before measurement. These findings provide evidence to suggest a mechanism
      linking increased polyol pathway activity and an increase in PLA2 activity to
      increased prostaglandin production, which is observed in diabetes of recent onset
      and may ultimately lead to changes associated with the development of diabetic
      nephropathy.

PMID- 9005968
TI  - Do non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes
      mellitus (IDDM) share genetic susceptibility loci? An analysis of putative IDDM
      susceptibility regions in familial NIDDM.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) has been viewed as genetically
      and physiologically distinct from insulin-dependent diabetes mellitus (IDDM), yet
      many of the recently suggested IDDM susceptibility loci are likely to increase
      the risk of diabetes through nonautoimmune mechanisms. To test the hypothesis
      that the IDDM susceptibility loci include important NIDDM susceptibility loci, we
      tested the linkage of 14 putative susceptibility regions with NIDDM among
      families and sibling pairs of Northern European descent. All regions were tested
      with highly informative microsatellite (simple tandem repeat) polymorphisms in up
      to 166 affected individuals from 42 families using both parametric and
      nonparametric methods (149 pairs for sibling pair analyses). We found no evidence
      for linkage to the majority of loci, including loci that appeared to be linked to
      IDDM in more than one study. We report some evidence for shared susceptibility
      for regions on chromosomes 1, 2, and 6. The best evidence based on multilocus
      affected pedigree member (APM) analysis of markers near D1S191 suggested linkage
      at P value .0001. This region has not yet been confirmed as an IDDM locus, and
      our analyses could represent a false-positive result. The role of these three
      regions will only be clarified by testing in additional families. In combination
      with other investigations in our laboratory for chromosome 11 susceptibility
      regions, our data generally do not provide convincing evidence that IDDM and
      NIDDM share common genetic factors among families of Northern European descent
      with ascertainment of two or more NIDDM siblings.

PMID- 9005969
TI  - Race and ethnicity determine serum insulin and C-peptide concentrations and
      hepatic insulin extraction and insulin clearance: comparative studies of three
      populations of West African ancestry and white Americans.
AB  - We examined the importance of ethnicity in terms of beta-cell secretion and
      hepatic insulin extraction (HIE) and insulin clearance (IC) to peripheral insulin
      levels before and after stimulation in three populations of West African
      ancestry, namely African-Americans, Ghanaian immigrants, and native Ghanaians
      living in diverse environments, and white Americans. Following 10 to 12 hours of
      overnight fasting, each subject ingested a 75-g oral glucose load. Blood samples
      for determination of serum glucose, insulin, and C-peptide were obtained at
      baseline and after the oral glucose load at 30-minute intervals for 240 minutes.
      Basal HIE and IC were calculated as the molar ratios of C-peptide and insulin
      concentrations at basal steady state, and postprandial values as molar ratios of
      the incremental integrated C-peptide and insulin areas. Clinical characteristics
      of the patients were not significantly different among the four groups. During
      the fasting and postprandial state, serum glucose levels were not significantly
      different among the four groups. Surprisingly, the mean fasting insulin
      concentration was significantly greater in native Ghanaians (21.19 +/- 0.93
      microU/mL, P < .05) than in African-Americans (11.90 +/- 1.02,microU/ML),
      Ghanaian immigrants (8.14 +/- 0.96 microU/mL), and white Americans (7.03 +/- 0.78
      microU/mL). Following the oral glucose load, the mean serum peak and incremental
      integrated areas of insulin were significantly (P < .05) greater in native
      Ghanaians, African-Americans, and Ghanaian immigrants compared with white
      Americans. In contrast, there were no significant differences in postprandial
      serum insulin responses among the three groups of West African ancestry,
      irrespective of country of origin or residence. Despite the higher insulin
      concentrations in blacks of West African ancestry compared with whites, the
      corresponding basal and postprandial serum C-peptide levels were not
      significantly different among the four groups. Mean basal and postprandial HIE
      and IC were significantly (P < .05 to .01) reduced (25% to 52%) in the three
      populations of West African ancestry compared with the white Americans, but these
      values were not significantly different among the West African descendants. When
      comparing metabolic responses in obese (body mass index [BMI] > 27 kg/m2) and non
      obese (BMI < 27 kg/m2) native Ghanaians, we found no significant differences in
      fasting insulin, C-peptide, and basal HIE or IC. Also, there were no significant
      relations between fasting and postprandial serum insulin, obesity indices, and
      HIE and IC in any of the groups. In summary, our study demonstrates that glucose
      tolerant native Ghanaians, Ghanaian immigrants, and African-Americans of West
      African ancestry manifest hyperinsulinemia and a decreased HIE and IC compared
      with white Americans. We conclude that race and ethnicity may be the major
      determinants of the mechanism(s) of beta-cell secretion, insulin action, and
      peripheral insulin levels and HIE or IC in humans. We speculate that the lower
      HIE and IC in blacks of West African descent appears to be a highly conserved
      metabolic trait irrespective of the country of residence.

PMID- 9005970
TI  - Sialic acid, diabetes, and aging: a study on the erythrocyte membrane.
AB  - Sialic acid (SA) content and Na+/K+-ATPase activity of red blood cell (RBC)
      membranes were studied in 26 normoalbuminuric patients with insulin-dependent
      diabetes mellitus (IDDM), 25 normoalbuminuric patients with non-insulin-dependent
      diabetes mellitus (NIDDM), and 40 healthy nondiabetic subjects with a negative
      family history for diabetes. A decrease in RBC membrane SA content and Na+/K+
      ATPase activity was observed in older control subjects compared with younger
      controls. A significant correlation between age, Na+/K+-ATPase activity, and SA
      content was also found. No difference was observed in RBC membrane SA content
      between IDDM and NIDDM subjects, but Na+/K+-ATPase activity was significantly
      lower in IDDM patients. SA content was increased in NIDDM subjects compared with
      healthy subjects of similar age, whereas Na+/K+-ATPase activity was significantly
      lower in both IDDM and NIDDM subjects compared with controls. In NIDDM, Na+/K+
      ATPase activity was significantly correlated with age, whereas both Na+/K+-ATPase
      activity and SA content were significantly correlated in IDDM and NIDDM patients.
      Hemoglobin A1c, (HbA1c) levels did not show any significant correlation either
      with Na+/K+-ATPase or with SA content in diabetic patients. The modified SA
      content and Na+/K+-ATPase activity in elderly subjects described in the present
      study indicate a similar behavior of the erythrocyte membrane during both RBC
      senescence and aging of subjects.

PMID- 9005971
TI  - Wortmannin converts insulin but not oxytocin from an antilipolytic to a lipolytic
      agent in the presence of forskolin.
AB  - Insulin is an important regulator of glucose transport and lipolysis in
      adipocytes. The present studies compared the effects of insulin in rat adipocytes
      with the effects of oxytocin and peroxovanadate, which mimic some effects of
      insulin. The antilipolytic effects of peroxovanadate and oxytocin were unaffected
      by 500 nmol/L wortmannin, which blocked the antilipolytic action of insulin.
      However, wortmannin, which is a relatively specific inhibitor of
      phosphatidylinositol 3-kinase, did block most of the stimulation of glucose
      metabolism by peroxovanadate while having little effect on that due to oxytocin.
      Under appropriate conditions, it was also possible to demonstrate a lipolytic
      action of insulin, especially with low (0.1 to 1 nmol/L) concentrations of
      insulin after exposure of adipocytes to 50 nmol/L wortmannin. The data provide
      additional support for the hypothesis that oxytocin and peroxovanadate affect
      adipose tissue metabolism by mechanisms distinctly different from those involved
      in insulin action.

PMID- 9005972
TI  - Dose-response for glucagonostatic effect of amylin in rats.
AB  - Glucagon secretion from pancreatic alpha cells is inhibited by insulin from beta
      cells. Amylin is a partner hormone to insulin cosecreted in response to nutrient
      stimuli, which, like insulin, inhibits beta-cell secretion. We investigated
      whether amylin also inhibits alpha-cell secretion of glucagon in response to
      infused L-arginine. Rat amylin (1.2, 3.6, 12, 36, or 120 pmol/kg/min; calculated
      plasma concentration, 13, 47, 195, 713, and 2,950 pmol/L, respectively; n = 7, 8,
      6, 4, and 7) or saline (n = 23) was infused into anesthetized male Harlan-Sprague
      Dawley rats during hyperinsulinemic-euglycemic clamps, which were used to
      equalize the influences of glucose and insulin on glucagon secretion. Plasma
      glucose and insulin concentrations and mean arterial pressures were not different
      between amylin- and saline-treated rats during a 10-minute 2-mmol L-arginine
      infusion delivered during the clamps. Plasma glucagon measurements taken during
      and after the arginine challenge showed that compared with saline infusions,
      amylin administration dose-dependently suppressed the glucagon response to
      arginine by a maximum of 62% (incremental area under the curve [AUC] 0 to 60
      minutes) with a plasma amylin EC50 of 18 pmol/L +/- 0.3 log units. These data
      indicate that amylin potently inhibits arginine-stimulated glucagon secretion.

PMID- 9005973
TI  - Myosin light-chain phosphorylation in diabetic cardiomyopathy in rats.
AB  - The regulatory myosin light chain (MLC) is phosphorylated in cardiac muscle by
      Ca2+/calmodulin-dependent MLC kinase (MLCK) and is considered to play a
      modulatory role in the activation of myofibrillar adenosine triphosphatase
      (ATPase) and the process of force generation. Since the depression in cardiac
      contractile function in chronic diabetes is associated with a decrease in
      myofibrillar ATPase activity, we investigated changes in MLC phosphorylation in
      diabetic heart. Rats were made diabetic by injecting streptozotocin (65 mg/kg
      intravenously), and the hearts were removed 8 weeks later; some 6-week diabetic
      animals were injected with insulin (3 U/d) for 2 weeks. Changes in the relative
      MLC and MLCK protein contents were measured by electrophoresis and immunoblot
      assay, whereas phosphorylated and unphosphorylated MLCs were separated on 10%
      acrylamide/urea gel and identified by Western blot. MLC and MLCK contents were
      decreased markedly (40% to 45%) and MLC phosphorylation was decreased
      significantly (30% to 45%) in the diabetic rat heart homogenate in comparison to
      control values. The changes in MLC and MLCK content in diabetic heart were
      partially reversible, whereas changes in MLC phosphorylation were normalized upon
      treatment with insulin. These results suggest that decreased protein contents of
      MLC and MLCK and phosphorylation of MLC may contribute to the depression of
      cardiac myofibriliar ATPase activity and heart dysfunction in diabetic
      cardiomyopathy.

PMID- 9005974
TI  - Acute effects of adrenaline on hepatic lipase secretion by rat hepatocytes.
AB  - Catecholamines are responsible for the daily changes in hepatic lipase (HL)
      expression associated with feeding and fasting. We have studied the mechanism by
      which adrenaline decreases HL secretion in suspensions of freshly isolated rat
      hepatocytes. Adrenaline acutely inhibited HL activity through activation of the
      alpha1-adrenergic pathway. The cells had significantly less HL activity in the
      presence of adrenaline versus cycloheximide, where protein de novo synthesis is
      completely blocked. The specific enzyme activity of secreted HL was not affected.
      Intracellular HL activity was decreased by adrenaline treatment. Pulse-labeling
      with [35S]methionine showed that de novo synthesis of the 53-kd endo-beta-N
      acetylglucosaminidase H (Endo H)-sensitive HL protein was unaffected by
      adrenaline. During subsequent chase of the control cells, the 53-kd form was
      converted to a 58-kd Endo H-resistant HL protein, which was rapidly secreted into
      the medium. In the presence of adrenaline, formation of the 58-kd protein was
      markedly reduced, whereas the 53-kd protein disappeared at a rate similar to the
      rate in controls. This suggests that part of the HL protein was degraded. In
      contrast to adrenaline, inhibition of HL secretion by colchicine was accompanied
      by an intracellular accumulation of HL activity and of the 58-kd protein. We
      conclude that adrenaline inhibits HL secretion posttranslationally by retarding
      the maturation of the 53-kd HL precursor to an active 58-kd protein, possibly by
      stimulating degradation of newly synthesized HL protein.

PMID- 9005975
TI  - Mechanisms underlying the negative growth hormone (GH) autofeedback on the GH
      releasing effect of hexarelin in man.
AB  - The growth hormone (GH) response to GH-releasing hormone (GHRH) is strongly
      inhibited by previous administration of recombinant human GH (rhGH), likely as a
      consequence of a somatostatin-mediated GH negative autofeedback. Hexarelin (HEX),
      a synthetic hexapeptide belonging to the GH-releasing peptide (GHRP) family,
      possesses a GH-releasing activity greater than that of GHRH both in animals and
      in man. The mechanism of action of GHRPs is yet to be completely clarified,
      although concomitant actions at the pituitary and hypothalamic level have been
      hypothesized. To further clarify the mechanisms of action underlying the GH
      releasing activity of HEX, in six normal young volunteers we studied the effects
      of rhGH (2 U intravenously [IV]) on the GH response either to GHRH (2 microg/kg
      IV) or to HEX (2 microg/kg IV) alone or combined with GHRH and/or pyridostigmine
      ([PD], 120 mg orally). The GH-releasing effect of HEX was higher than that of
      GHRH (area under the curve [AUC], 2,200.8 +/- 256.9 v 792.2 +/- 117.6 microg/L/h,
      P < .001), whereas combined administration of the two substances induced a true
      synergistic effect, with GH release after HEX plus GHRH (4,259.2 +/- 308.0
      microg/L/h) being higher (P < .02) than the arithmetic sum of the GH increases
      induced by each compound separately administered. After rhGH administration, the
      GH-releasing effect of HEX was blunted (1,468.9 +/- 193.7 microg/L/h, P < .04;
      inhibition of 32.1%), whereas that of GHRH was nearly abolished (102.0 +/- 7.8
      microg/L/h, P < .02; inhibition of 86.1%). The GH response to combined
      administration of HEX and GHRH was also blunted by the previous rhGH bolus
      (3,070.6 +/- 481.8 microg/L/h, P < .02; inhibition of 26.7%). PD did not modify
      the GH-releasing effect of HEX either alone (2,456.8 +/- 317.5 microg/L/h) or
      combined with GHRH (4,009.1 +/- 360.8 microg/L/h). rhGH was again able to blunt
      the GH response to HEX combined with PD (1,619.3 +/- 237.9 microg/L/h, P < .02),
      but failed to modify the GH response to HEX combined with GHRH and PD (4,548.4 +/
      698.0 microg/L/h). In conclusion, these results demonstrate that rhGH
      administration only blunts the GH-releasing activity of HEX, but abolishes that
      of GHRH. The blunting effect of rhGH on the GH response to HEX is probably
      mediated by a concomitant reduction in the activity of GHRH-secreting neurons and
      an increase of somatostatinergic tone.

PMID- 9005976
TI  - Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1
      29) in healthy elderly men.
AB  - Age-related reductions in growth hormone (GH) and insulin-like growth factor-I
      (IGF-I) may contribute to decreased muscle mass and strength in older persons.
      The relationship of this phenomenon to skeletal muscle bioenergetics has not been
      reported. We sought to determine whether administration of GH-releasing hormone
      (GHRH) would sustain increases in GH and IGF-I and improve skeletal muscle
      function and selected measures of body composition and metabolism. We measured GH
      secretion, muscle strength, muscle histology, and muscle energy metabolism by
      phosphorus nuclear magnetic resonance spectroscopy (31P-NMRS), body composition,
      and endocrine-metabolic functions before and after 6 weeks of treatment. Eleven
      healthy, ambulatory, non-obese men aged 64 to 76 years with low baseline IGF-I
      levels were treated at home as outpatients by nightly subcutaneous self
      injections of 2 mg GHRH for 6 weeks. We measured GH levels in blood samples
      obtained every 20 minutes from 8:00 PM to 8:00 AM; AM serum levels of IGF-I, IGF
      binding protein-3 (IGFBP-3), and GH binding protein (GHBP); muscle strength;
      muscle histology; the normalized phosphocreatine abundance, PCr/[PCr + Pi], and
      intracellular pH in forearm muscle by NMRS during both sustained and ramped
      exercise; body composition by dual-energy x-ray absorptiometry (DEXA); lipid
      levels; and glucose, insulin, and GH levels during an oral glucose tolerance test
      (OGTT). GHRH treatment increased mean nocturnal GH release (P < .02), the area
      under the GH peak ([AUPGH] P < .006), and GH peak amplitude (P < .05), with no
      change in GH pulse frequency or in levels of IGF-I, IGFBP-3, or GHBP Two of six
      measures of muscle strength, upright row (P < .02) and shoulder press (P < .04),
      and a test of muscle endurance, abdominal crunch (P < .03), improved. GHRH
      treatment did not alter exercise-mediated changes in PCr/[PCr + Pi] or
      intracellular pH, but decreased or abolished significant relationships between
      changes in PCr/[PCr + Pi] or pH and indices of muscle strength. GHRH treatment
      did not change weight, body mass index, waist to hip ratio, DEXA measures of
      muscle and fat, muscle histology, glucose, insulin, or GH responses to OGTT, or
      lipids. No significant adverse effects were observed. These data suggest that
      single nightly doses of GHRH are less effective than multiple daily doses of GHRH
      in eliciting GH- and/or IGF-I-mediated effects. GHRH treatment may increase
      muscle strength, and it alters baseline relationships between muscle strength and
      muscle bioenergetics in a manner consistent with a reduced need for anaerobic
      metabolism during exercise. Thus, an optimized regimen of GHRH administration
      might attenuate some of the effects of aging on skeletal muscle function in older
      persons.

PMID- 9005977
TI  - Dissociated insulinotropic sensitivity to glucose and carbachol in high-fat diet
      induced insulin resistance in C57BL/6J mice.
AB  - To study islet function following reduced insulin sensitivity, we examined mice
      of the C57BL/6J strain, the genotype of which carries an increased propensity to
      develop insulin resistance when metabolically challenged. The mice received
      either a high-fat diet (58% fat on an energy basis) or a control diet (11% fat)
      for 12 weeks. The body weight of mice on the high-fat diet increased
      significantly more than that of mice on the control diet (25.8 +/- 0.4 v 21.3 +/-
      0.2 g, P < .001). Already after 1 week on the high-fat diet, a significant
      hyperglycemia accompanied by hyperinsulinemia had evolved, indicative of insulin
      resistance. After 12 weeks, plasma glucose levels for high-fat diet-treated mice
      were 7.5 +/- 0.1 mmol/L, versus 6.5 +/- 0.1 mmol/L in controls (P < .001);
      corresponding values for plasma insulin were 248 +/- 17 and 104 +/- 7 pmol/L,
      respectively (P < .001). Mice given a high-fat diet also had elevated levels of
      total cholesterol, triglycerides, and free fatty acids (FFAs) compared with
      controls. After 4, 8, and 12 weeks, glucose (2.8, 8.3, or 16.7 mmol/kg) or the
      cholinergic agonist carbachol (0.16 or 0.53 micromol/kg) was injected
      intraperitoneally. The insulinotropic response to glucose was not different
      between the two groups after 4 or 8 weeks, whereas after 12 weeks, glucose
      induced insulin secretion was markedly impaired in high-fat diet-treated mice (P
      < .001). In contrast, after 8 and 12 weeks on a high-fat diet, carbachol
      stimulated insulin secretion was potentiated (P < .01), whereas carbachol
      stimulated glucagon secretion was not significantly altered. Furthermore, after
      12 weeks on the high-fat diet, insulin secretion from isolated islets was
      impaired at glucose levels of 8.3, 11.1, and 16.7 mmol/L (P < or = .05).
      Moreover, islet morphology as examined by immunocytochemistry using insulin
      antibodies and islet innervation, as revealed by immunostaining of tyrosine
      hydroxylase (TH), neuropeptide Y (NPY), galanin, vasoactive intestinal
      polypeptide (VIP), and substance P (SP) were unaffected by the high-fat diet for
      12 weeks. However, quantitative in situ hybridization showed a 3.5-fold
      upregulation of insulin gene expression in response to the high-fat diet (P <
      .001) despite unaltered B-cell mass and pancreatic insulin content. We conclude
      that as little as 1 week of treatment with a high-fat diet induces insulin
      resistance in C57BL/6J mice. This is accompanied later by hyperlipemia,
      potentiated carbachol-stimulated insulin secretion, and increased insulin gene
      expression but impaired glucose-stimulated insulin secretion. We suggest that
      after several weeks' duration, insulin resistance is accompanied by enhanced
      islet sensitivity to cholinergic activation and exaggerated insulin gene
      expression, whereas the failing islet sensitivity to glucose represents
      decompensation.

PMID- 9005979
TI  - Induction of mRNAs for the growth hormone receptor gene during mouse 3T3-L1
      preadipocyte differentiation.
AB  - Adipose tissue is a growth hormone (GH)-responsive tissue in which GH regulates
      energy metabolism. GH exerts its effect by interacting with its specific GH
      receptor (GHR). In rodents, alternative splicing of the nascent transcript from
      the GHR gene produces two major transcripts: GHR mRNA and GHR binding protein
      (GHBP) mRNA. These two transcripts share the common extracellular ligand-binding
      domain, but differ in the C-terminal sequence. Since GHR plays an important role
      in mediating the actions of GH in adipose metabolism, we initiated these studies
      to examine GHR gene expression in the course of mouse 3T3-L1 preadipocyte
      adipocyte conversion. GHR and GHBP transcripts were detected by RNase protection
      assay (RPA) using the antisense riboprobes complementary either to the specific
      sequence of the GHR or to the sequence shared by both GHR and GHBP mRNAs. After
      stimulation of differentiation, mRNA abundance increased 28-fold and reached a
      maximal level by day 7 of adipogenesis. The GHR mRNA:GHBP mRNA ratio was 1.1 +/-
      0.12 and remained unchanged during differentiation. The decay rate for both
      mRNAs, estimated by treating the cells with actinomycin D, was approximately 24
      hours and showed no significant difference between preadipocytes and adipocytes.
      Thus, GHR gene expression is dramatically upregulated during preadipocyte
      adipocyte differentiations.

PMID- 9005980
TI  - Host/pathogen interactions: series introduction.

PMID- 9005978
TI  - Evaluation of hormonal function in a series of incidentally discovered adrenal
      masses.
AB  - The discovery of an asymptomatic adrenal mass (incidentaloma) during the
      investigation of an unrelated condition is relatively common. In this study, we
      report the clinical, radiologic, and endocrine evaluation of 38 patients (22
      women and 16 men aged 24 to 84 years) with adrenal incidentaloma (size, 1 to 12
      cm). The patients underwent basal and dynamic evaluation of the hypothalamic
      pituitary-adrenal (HPA) axis, renin-angiotensin-aldosterone system, and
      adrenomedullary function. Moreover, computed tomograpy (CT) scan and 131I-6beta
      iodomethyl-19-norcholest-5(10)-en-3beta-ol(NP-59) and/or 131I
      metaiodobenzylguanidine (MIBG) scintigraphy were performed. The endocrine
      evaluation indicated two cases of pheochromocytoma and four cases of preclinical
      Cushing's syndrome, three of which underwent surgery with histologic diagnosis of
      two adrenocortical adenomas and one carcinoma. Low levels of serum
      dehydroepiandrosterone sulfate (DHEA-S), associated with a markedly increased 17
      hydroxyprogesterone (17-OHP) response to a corticotropin (ACTH) test, were found
      in patients with incidentaloma. On the basis of endocrine and morphologic data,
      13 patients underwent surgical treatment: five adrenocortical adenomas (two
      functioning), two pheochromocytomas, two ganglioneuromas, one cortisol-secreting
      adrenal carcinoma, one lymphangiomatous cyst, one myelolipoma, and one hemorrhage
      were found. Careful diagnostic assessment of incidentally discovered adrenal
      masses must be performed to exclude the presence of malignant and/or functioning
      lesions and to verify the possibility that patients with incidentaloma have a
      genetic or acquired deficit of adrenal steroidogenic activity.

PMID- 9005981
TI  - Complex oscillatory heart rhythm: a dance macabre.

PMID- 9005982
TI  - Selectin ligands: will the real ones please stand up?

PMID- 9005983
TI  - Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic
      pathway in human skeletal muscle.
AB  - Previous studies provided evidence that sepsis-induced muscle proteolysis in
      experimental animals is caused by increased ubiquitin-proteasome-dependent
      protein breakdown. It is not known if a similar mechanism accounts for muscle
      proteolysis in patients with sepsis. We determined mRNA levels for ubiquitin and
      the 20 S proteasome subunit HC3 by Northern blot analysis in muscle tissue from
      septic (n = 7) and non-septic (n = 11) patients. Plasma and muscle amino acid
      concentrations and concentrations in urine of 3-methylhistidine (3-MH),
      creatinine, and cortisol were measured at the time of surgery to assess the
      catabolic state of the patients. A three- to fourfold increase in mRNA levels for
      ubiquitin and HC3 was noted in muscle tissue from the septic patients concomitant
      with increased muscle levels of phenylalanine and 3-MH and reduced levels of
      glutamine. Total plasma amino acids were decreased by approximately 30% in the
      septic patients. The 3-MH/creatinine ratio in urine was almost doubled in septic
      patients. The cortisol levels in urine were higher in septic than in control
      patients but this difference did not reach statistical significance. The results
      suggest that sepsis is associated with increased mRNAs of the ubiquitin
      proteasome pathway in human skeletal muscle.

PMID- 9005984
TI  - Shared gamma(c) subunit within the human interleukin-7 receptor complex. A
      molecular basis for the pathogenesis of X-linked severe combined
      immunodeficiency.
AB  - Genetic evidence suggests that mutations in the gamma(c) receptor subunit cause X
      linked severe combined immunodeficiency (X-SCID). The gamma(c) subunit can be
      employed in receptor complexes for IL-2, -4, -7, -9, and -15, and the multiple
      signaling defects that would result from a defective gamma(c) chain in these
      receptors are proposed to cause the severe phenotype of X-SCID patients.
      Interestingly, gene disruption of either IL-7 or the IL-7 receptor (IL-7R) alpha
      subunit in mice leads to immunological defects that are similar to human X-SCID.
      These observations suggest the functional importance of gamma(c) in the IL-7R
      complex. In the present study, structure/function analyses of the IL-7R complex
      using a chimeric receptor system demonstrated that gamma(c) is indeed critical
      for IL-7R function. Nonetheless, only a limited portion of the cytoplasmic domain
      of gamma(c) is necessary for IL-7R signal transduction. Furthermore, replacement
      of the gamma(c) cytoplasmic domain by a severely truncated erythropoeitin
      receptor does not affect measured IL-7R signaling events. These findings support
      a model in which gamma(c) serves primarily to activate signal transduction by the
      IL-7R complex, while IL-7R alpha determines specific signaling events through its
      association with cytoplasmic signaling molecules. Finally, these studies are
      consistent with the hypothesis that the molecular pathogenesis of X-SCID is due
      primarily to gamma(c)-mediated defects in the IL-7/IL-7R system.

PMID- 9005985
TI  - Chemokine receptor usage by human eosinophils. The importance of CCR3
      demonstrated using an antagonistic monoclonal antibody.
AB  - Chemokines bind and signal through G-protein coupled seven transmembrane
      receptors. Various chemokine receptors are expressed on leukocytes, and these may
      impart selective homing of leukocyte subsets to sites of inflammation. Human
      eosinophils express the eotaxin receptor, CCR3, but respond to a variety of CC
      chemokines apart from eotaxin, including RANTES, monocyte chemotactic protein
      (MCP)-2, MCP-3, and MCP-4. Here we describe a mAb, 7B11, that is selective for
      CCR3 and has the properties of a true receptor antagonist. 7B11 blocked binding
      of various radiolabeled chemokines to either CCR3 transfectants, or eosinophils.
      Pretreatment of eosinophils with this mAb blocked chemotaxis and calcium flux
      induced by all CCR3 ligands. In all individuals examined, including allergic and
      eosinophilic donors, > 95% of the response of eosinophils to eotaxin, RANTES, MCP
      2, MCP-3, and MCP-4 was shown to be mediated through CCR3. The IL-8 receptors,
      particularly CXCR2, were induced on IL-5 primed eosinophils, however these
      eosinophils responded to CC chemokines in the same manner as unprimed
      eosinophils. These results demonstrate the importance of CCR3 for eosinophil
      responses, and the feasibility of completely antagonizing this receptor.

PMID- 9005987
TI  - Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal
      cyst cells supports a loss-of-function model for cyst pathogenesis.
AB  - It is not known whether mutations in the PKD1 gene cause autosomal dominant
      polycystic kidney disease (PKD) by an activating (gain-of-function) or an
      inactivating (loss-of-function) model. We analyzed DNA from cyst epithelial cells
      for loss of heterozygosity (LOH) in the PKD1 region of chromosome 16p13 using
      microsatellite markers. 29 cysts from four patients were studied. Five cysts from
      three patients had chromosome 16p13 LOH. Four of the cysts had loss of two
      chromosome 16p13 markers that flank the PKD1 gene. In two patients,
      microsatellite analysis of family members was consistent with loss of the wild
      type copy of PKD1 in the cysts. In the third patient, 16p13 LOH was detected in
      three separate cysts, all of which showed loss of the same alleles. Chromosome
      3p21 LOH was detected in one cyst. No LOH was detected in four other genomic
      regions. These results demonstrate that some renal cyst epithelial cells exhibit
      clonal chromosomal abnormalities with loss of the wild-type copy of PKD1. This
      supports a loss-of-function model for autosomal dominant PKD, with a germline
      mutation inactivating one copy of PKD1 and somatic mutation or deletion
      inactivating the remaining wild-type copy.

PMID- 9005986
TI  - Voltage-gated calcium channel currents in human coronary myocytes. Regulation by
      cyclic GMP and nitric oxide.
AB  - Voltage-gated Ca2+ channels contribute to the maintenance of contractile tone in
      vascular myocytes and are potential targets for vasodilating agents. There is no
      information available about their nature and regulation in human coronary
      arteries. We used the whole-cell voltage-clamp technique to characterize Ca2+
      channel currents immediately after enzymatic dissociation and after primary
      culture of coronary myocytes taken from heart transplant patients. We recorded a
      dihydropyridine-sensitive L-type current in both freshly isolated and primary
      cultured cells. A T-type current was recorded only in culture. The L- (but not
      the T-) type current was inhibited by permeable analogues of cGMP in a dose
      dependent manner. This effect was mimicked by the nitric oxide-generating agents
      S-nitroso-N-acetylpenicillamine (SNAP) and 3-morpholinosydnonimine which
      increased intracellular cGMP. Methylene blue, known to inhibit guanylate cyclase,
      antagonized the effect of SNAP. Inhibitions by SNAP and cGMP were not additive
      and seemed to occur through a common pathway. We conclude that (a) L-type Ca2+
      channels are the major pathway for voltage-gated Ca2+ entry in human coronary
      myocytes; (b) their inhibition by agents stimulating nitric oxide and/or
      intracellular cGMP production is expected to contribute to vasorelaxation and may
      be involved in the therapeutic effect of nitrovasodilators; and (c) the
      expression of T-type Ca2+ channels in culture may be triggered by cell
      proliferation.

PMID- 9005988
TI  - Impaired arterial neointima formation in mice with disruption of the plasminogen
      gene.
AB  - To define the role of plasminogen (Plg) in the smooth muscle cell response after
      arterial wall injury, neointima formation was evaluated after electric injury of
      the femoral artery in plasminogen-deficient (Plg-/-) mice. The injury destroyed
      all medial smooth muscle cells, denuded the injured segment of intact
      endothelium, and induced transient platelet-rich mural thrombosis. In wild-type
      (Plg+/+) mice, vascular wound healing was characterized by lysis of the thrombus,
      transient infiltration of inflammatory cells, and progressive removal of necrotic
      debris and thrombosis. Topographic analysis revealed repopulation of the media
      and accumulation in the neointima of smooth muscle cells originating from the
      noninjured borders, which progressed into the necrotic center. In Plg-/- mice,
      wound healing was significantly impaired with delayed removal of necrotic debris,
      reduced leucocyte infiltration and smooth muscle cell accumulation, and decreased
      neointima formation. Smooth muscle cells accumulated at the uninjured borders,
      but failed to migrate into the necrotic center. Proliferation of smooth muscle
      cells was not affected by Plg deficiency. Evans blue staining revealed no
      genotypic differences in reendothelialization. Thus, Plg plays a significant role
      in vascular wound healing and arterial neointima formation after injury, most
      likely by affecting cellular migration.

PMID- 9005989
TI  - Established immunity precludes adenovirus-mediated gene transfer in rat carotid
      arteries. Potential for immunosuppression and vector engineering to overcome
      barriers of immunity.
AB  - Preclinical arterial gene transfer studies with adenoviral vectors are typically
      performed in laboratory animals that lack immunity to adenovirus. However, human
      patients are likely to have prior exposures to adenovirus that might affect: (a)
      the success of arterial gene transfer; (b) the duration of recombinant gene
      expression; and (c) the likelihood of a destructive immune response to transduced
      cells. We confirmed a high prevalence (57%) in adult humans of neutralizing
      antibodies to adenovirus type 5. We then used a rat model to establish a central
      role for the immune system in determining the success as well as the duration of
      recombinant gene expression after adenovirus-mediated gene transfer into isolated
      arterial segments. Vector-mediated recombinant gene expression, which was
      successful in naive rats and prolonged by immunosuppression, was unsuccessful in
      the presence of established immunity to adenovirus. 4 d of immunosuppressive
      therapy permitted arterial gene transfer and expression in immune rats, but at
      decreased levels. Ultraviolet-irradiated adenoviral vectors, which mimic advanced
      generation vectors (reduced viral gene expression and relatively preserved capsid
      function), were less immunogenic than were nonirradiated vectors. A primary
      exposure to ultraviolet-irradiated (but not nonirradiated) vectors permitted
      expression of a recombinant gene after redelivery of the same vector. In
      conclusion, arterial gene transfer with current type 5 adenoviral vectors is
      unlikely to result in significant levels of gene expression in the majority of
      humans. Both immunosuppression and further engineering of the vector genome to
      decrease expression of viral genes show promise in circumventing barriers to
      adenovirus-mediated arterial gene transfer.

PMID- 9005991
TI  - Transit time heterogeneity in canine small intestine: significance for oxygen
      transport.
AB  - We previously found that local O2 extraction efficacy in isolated pump-perfused
      intestine was enhanced when systemic reflex vasoconstriction was stimulated by
      hypovolemia (Samsel, R.W., and P.T. Schumacker. 1994. J. Appl. Physiol. 77: 2291
      2298). The microvascular mechanism underlying this beneficial effect could
      involve a redistribution of flow between mucosa and serosa, or an adjustment in
      the heterogeneity of perfusion within those regions. We measured regional blood
      flows and distributions of flow and capillary erythrocyte transit times in two
      segments of small intestine in anesthetized dogs (n = 10). Each vascularly
      isolated segment of intestine was pump-perfused under high flow (O2 supply
      independent VO2) and low flow (O2 supply-dependent) conditions. During the first
      gut segment, the animal was kept normovolemic using i.v. fluids to minimize
      reflex vasoconstriction. During the second, the animal was hemorrhaged to augment
      vasoconstriction (n = 7), or kept normovolemic to control for the effects of time
      (n = 3). Blood flow distributions were measured using 15 microm radiolabeled
      microspheres. Tissue blood volume was measured using 99mTc-labeled red blood
      cells. Capillary volume was determined as the product of tissue blood volume and
      the histologically derived fraction of vascular volume in the capillaries.
      Transit times were calculated as the ratio of capillary volume to flow. Each gut
      segment was fixed and sectioned into 350 approximately 100 mg tissue pieces for
      analysis. Data revealed significant spatial heterogeneity of blood flow and
      capillary transit times in both mucosa and muscularis, with relative dispersions
      (SD/Mean) ranging from 23 to 97%. Hypovolemia caused an increase in flow
      heterogeneity in muscularis at both high and low flow states, and in mucosa under
      high flow conditions. However, hypovolemia also elicited changes in capillary
      volume, such that transit time heterogeneity remained unchanged. Augmentation of
      vasoconstrictor tone caused a redistribution of flow toward mucosa (P < 0.003)
      under high and low flow conditions. This redistribution correlated with the
      improvements in O2 extraction ratio (P = 0.022). Thus, the improvement in gut O2
      extraction efficacy seen with increased vasoconstriction may be explained mostly
      by an intramural redistribution of flow between mucosa and muscularis. Capillary
      transit time heterogeneity remained unchanged, suggesting that this variable is
      tightly regulated.

PMID- 9005990
TI  - Deficiency of Src family kinases Fgr and Hck results in activation of erythrocyte
      K/Cl cotransport.
AB  - Src-family kinases play a central role in regulation of hematopoietic cell
      functions. We found that mouse erythrocytes express the Src-family kinases Fgr
      and Hck, as well as Lyn. To directly test whether Fgr and Hck play any role in
      erythrocyte function, we analyzed red cells isolated from fgr-/-, hck-/-, and fgr
      /- hck-/- knock-out mice. Mean corpuscular hemoglobin concentration and median
      density are increased, while K content is decreased, in fgr-/- hck-/- double
      mutant erythrocytes compared with wild-type, fgr-/-, or hck-/- erythrocytes. Na/K
      pump and Na/K/Cl cotransport were not altered, but K/Cl cotransport activity was
      significantly and substantially higher (approximately three-fold) in fgr-/- hck-/
      double-mutant erythrocytes. This enhanced K/Cl cotransport activity did not
      depend on cell age. In fact, in response to bleeding, K/Cl cotransport activity
      increased in parallel with reticulocytosis in wild-type erythrocytes, while
      abnormal K/Cl cotransport did not change as a consequence of reticulocytosis in
      fgr-/- hck-/- double-mutant erythrocytes. Okadaic acid, an inhibitor of a
      phosphatase that has been implicated in activation of the K/Cl cotransporter,
      inhibited K/Cl cotransport in wild-type and fgr-/- hck-/- double-mutant
      erythrocytes to a comparable extent. In contrast, staurosporine, an inhibitor of
      a kinase that has been suggested to negatively regulate this same phosphatase
      enhanced K/Cl cotransport in wild-type but not in fgr-/- hck-/- double-mutant
      erythrocytes. On the basis of these findings, we propose that Fgr and Hck are the
      kinases involved in the negative regulation of the K/Cl cotransporter-activating
      phosphatase. Abnormality of erythrocyte K/Cl cotransport in fgr-/- hck-/- double
      mutant animals represents the first demonstration that Src-family kinases may be
      involved in regulation of membrane transport.

PMID- 9005993
TI  - Dramatic neuronal rescue with prolonged selective head cooling after ischemia in
      fetal lambs.
AB  - Hypothermia has been proposed as a neuroprotective strategy. However, short-term
      cooling after hypoxia-ischemia is effective only if started immediately during
      resuscitation. The aim of this study was to determine whether prolonged head
      cooling, delayed into the late postinsult period, improves outcome from severe
      ischemia. Unanesthetized near term fetal sheep were subject to 30 min of cerebral
      ischemia. 90 min later they were randomized to either cooling (n = 9) or sham
      cooling (n = 7) for 72 h. Intrauterine cooling was induced by a coil around the
      fetal head, leading initially to a fall in extradural temperature of 5-10 degrees
      C, and a fall in esophageal temperature of 1.5-3 degrees C. Cooling was
      associated with mild transient systemic metabolic effects, but not with
      hypotension or altered fetal heart rate. Cerebral cooling reduced secondary
      cortical cytotoxic edema (P < 0.001). After 5 d of recovery there was greater
      residual electroencephalogram activity (-5.2+/-1.6 vs. -15.5+/-1.5 dB, P < 0.001)
      and a dramatic reduction in the extent of cortical infarction and neuronal loss
      in all regions assessed (e.g., 40 vs. 99% in the parasagittal cortex, P < 0.001).
      Selective head cooling, maintained throughout the secondary phase of injury, is
      noninvasive and safe and shows potential for improving neonatal outcome after
      perinatal asphyxia.

PMID- 9005992
TI  - EWS-Fli1 antisense oligodeoxynucleotide inhibits proliferation of human Ewing's
      sarcoma and primitive neuroectodermal tumor cells.
AB  - The translocation t(11;22) is a common chromosomal abnormality detected both in
      Ewing's sarcoma and in primitive neuroectodermal tumor cells. The translocation
      results in an EWS-Fli1 fusion gene, made up of the 5' half of the EWS gene on
      chromosome 22 fused to the 3' half of the Fli1 gene on chromosome 11. Recent
      studies have evaluated possible roles of the fusion gene products. However, the
      biological significance of EWS-Fli1 is still unknown. Using a competitive
      polymerase chain reaction technique, we show here that there might be a
      correlation between the expression levels of the EWS-Fli1 fusion gene and the
      proliferative activities of Ewing's sarcoma and primitive neuroectodermal tumor
      cells. When the EWS-Fli1 expression is inhibited by antisense
      oligodeoxynucleotides against the fusion RNA, the growth of the tumor cells is
      significantly reduced both in vitro and in vivo. The data further indicate the
      growth inhibition of the cells by the antisense sequence might be mediated by
      G0/G1 block in the cell cycle progression. These results suggest that EWS-Fli1
      may play an important role in the proliferation of the tumor cells, and the EWS
      Fli1 fusion RNA could be used as a target to inhibit the growth of Ewing's
      sarcoma and primitive neuroectodermal tumor with the specific antisense
      oligonucleotide.

PMID- 9005994
TI  - Priming of human CD4+ antigen-specific T cells to undergo apoptosis by HIV
      infected monocytes. A two-step mechanism involving the gp120 molecule.
AB  - The study of the pathology of HIV-1 infection in chimpanzees supports the idea of
      the crucial role of HIV-infected monocytes in the pathogenesis of AIDS, although
      viral mechanisms that lead to T cell dysfunction and deletion during HIV
      infection are still unclear. We show here that HIV-1-infected antigen-presenting
      monocytes (APCs) are able to prime in vitro non-HIV-infected antigen-specific
      CD4+ T cell lines or peripheral blood CD4+ T cells to undergo apoptosis after
      antigen-specific restimulation. The priming of T cells for apoptosis occurs in
      the absence of HIV replication in the T cells. Priming for apoptosis required two
      concomitant signals present on the same APC, an antigenic stimulus and a second
      signal provided by the HIV gp120 protein as demonstrated by the use as APCs of
      EBV-LCLs infected with different recombinant deleted proviruses or transfected
      with different HIV proteins. These results provide a mechanism for the priming
      for apoptosis of T cells in HIV-infected patients, implicating a role for HIV
      infected APCs in the induction of T cell dysfunction and depletion in AIDS.

PMID- 9005996
TI  - Important role of tissue angiotensin-converting enzyme activity in the
      pathogenesis of coronary vascular and myocardial structural changes induced by
      long-term blockade of nitric oxide synthesis in rats.
AB  - The long-term administration of N(omega)-nitro-L-arginine methyl ester (L-NAME),
      an inhibitor of nitric oxide synthesis, produces coronary vascular remodeling and
      myocardial hypertrophy in animals. This study used a rat model to investigate the
      role of angiotensin I converting enzyme (ACE) in the pathogenesis of such
      changes. We studied the following groups, all of which received drug treatment in
      their drinking water: untreated controls, and those administered L-NAME, L-NAME,
      and an ACE inhibitor (ACEI), and L-NAME and hydralazine. Cardiovascular
      structural changes and tissue ACE activities were evaluated after the first,
      fourth, and eighth week of treatment. In rats treated with L-NAME alone, vascular
      remodeling was evident at the fourth and eighth week, and myocardial hypertrophy
      was present at the eighth week of treatment. The vascular and myocardial
      remodeling were characterized by increased tissue ACE activities and
      immunodetectable ACE in those tissues. These changes were markedly reduced by
      ACEI, but not by hydralazine treatment. Increased local ACE expression may thus
      be important in the pathogenesis of cardiovascular remodeling in this model.

PMID- 9005995
TI  - Mutation of a highly conserved residue of betaI spectrin associated with fatal
      and near-fatal neonatal hemolytic anemia.
AB  - We studied an infant with severe nonimmune hemolytic anemia and hydrops fetalis
      at birth. His neonatal course was marked by ongoing hemolysis of undetermined
      etiology requiring repeated erythrocyte transfusions. He has remained transfusion
      dependent for more than 2 yr. A previous sibling born with hemolytic anemia and
      hydrops fetalis died on the second day of life. Peripheral blood smears from the
      parents revealed rare elliptocytes. Examination of their erythrocyte membranes
      revealed abnormal mechanical stability as well as structural and functional
      abnormalities in spectrin. Genetic studies revealed that the proband and his
      deceased sister were homozygous for a mutation of betaIsigma1 spectrin, L2025R,
      in a region of spectrin that is critical for normal function. The importance of
      leucine in this position of the proposed triple helical model of spectrin repeats
      is highlighted by its evolutionary conservation in all beta spectrins from
      Drosophila to humans. Molecular modeling demonstrated the disruption of
      hydrophobic interactions in the interior of the triple helix critical for
      spectrin function caused by the replacement of the hydrophobic, uncharged leucine
      by a hydrophilic, positively charged arginine. This mutation must also be
      expressed in the betaIsigma2 spectrin found in muscle, yet pathologic and
      immunohistochemical examination of skeletal muscle from the deceased sibling was
      unremarkable.

PMID- 9005998
TI  - Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin
      D receptor that results in decreased affinity for hormone and cellular
      hyporesponsiveness.
AB  - Mutations in the vitamin D receptor (VDR) result in target organ resistance to
      1alpha,25-dihydroxyvitamin D [1,25(OH)2D3], the active form of vitamin D, and
      cause hereditary 1,25-dihydroxyvitamin D resistant rickets (HVDRR). We analyzed
      the VDR of a patient who exhibited three genetic diseases: HVDRR, congenital
      total lipodystrophy, and persistent mullerian duct syndrome. The patient was
      treated with extremely high dose calcitriol (12.5 microg/d) which normalized
      serum calcium and improved his rickets. Analysis of [3H]1,25(OH)2D3 binding in
      the patient's cultured fibroblasts showed normal abundance of VDR with only a
      slight decrease in binding affinity compared to normal fibroblasts when measured
      at 0 degrees C. The patient's fibroblasts demonstrated 1,25(OH)2D3-induction of
      24-hydroxylase mRNA, but the effective dose was approximately fivefold higher
      than in control cells. Sequence analysis of the patient's VDR gene uncovered a
      single point mutation, H305Q. The recreated mutant VDR was transfected into COS-7
      cells where it was 5 to 10-fold less responsive to 1,25(OH)2D3 in gene
      transactivation. The mutant VDR had an eightfold lower affinity for
      [3H]1,25(OH)2D3 than the normal VDR when measured at 24 degrees C. RFLP
      demonstrated that the patient was homozygous for the mutation while the parents
      were heterozygous. In conclusion, we describe a new ligand binding domain
      mutation in the VDR that causes HVDRR due to decreased affinity for 1,25(OH)2D3
      which can be effectively treated with extremely high doses of hormone.

PMID- 9005999
TI  - Quasiperiodicity and chaos in cardiac fibrillation.
AB  - In cardiac fibrillation, disorganized waves of electrical activity meander
      through the heart, and coherent contractile function is lost. We studied
      fibrillation in three stationary forms: in human chronic atrial fibrillation, in
      a stabilized form of canine ventricular fibrillation, and in fibrillation-like
      activity in thin sheets of canine and human ventricular tissue in vitro. We also
      created a computer model of fibrillation. In all four studies, evidence indicated
      that fibrillation arose through a quasiperiodic stage of period and amplitude
      modulation, thus exemplifying the "quasiperiodic transition to chaos" first
      suggested by Ruelle and Takens. This suggests that fibrillation is a form of
      spatio-temporal chaos, a finding that implies new therapeutic approaches.

PMID- 9006000
TI  - Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of
      phospholipids.
AB  - Lipopolysaccharide binding protein (LBP) is a plasma protein known to facilitate
      the diffusion of bacterial LPS (endotoxin). LBP catalyzes movement of LPS
      monomers from LPS aggregates to HDL particles, to phospholipid bilayers, and to a
      binding site on a second plasma protein, soluble CD14 (sCD14). sCD14 can hasten
      transfer by receiving an LPS monomer from an LPS aggregate, and then surrendering
      it to an HDL particle, thus acting as a soluble "shuttle" for an insoluble lipid.
      Here we show that LBP and sCD14 shuttle not only LPS, but also phospholipids.
      Phosphatidylinositol (PI), phosphatidylcholine, and a fluorescently labeled
      derivative of phosphatidylethanolamine (R-PE) are each transferred by LBP from
      membranes to HDL particles. The transfer could be observed using recombinant LBP
      and sCD14 or whole human plasma, and the plasma-mediated transfer of PI could be
      blocked by anti-LBP and partially inhibited by anti-CD14. sCD14 appears to act as
      a soluble shuttle for phospholipids since direct binding of PI and R-PE to sCD14
      was observed and because addition of sCD14 accelerated transfer of these lipids.
      These studies define a new function for LBP and sCD14 and describe a novel
      mechanism for the transfer of phospholipids in blood. In further studies, we show
      evidence suggesting that LBP transfers LPS and phospholipids by reciprocal
      exchange: LBP-catalyzed binding of R-PE to LPS x sCD14 complexes was accompanied
      by the exit of LPS from sCD14, and LBP-catalyzed binding of R-PE to sCD14 was
      accelerated by prior binding of LPS to sCD14. Binding of one lipid is thus
      functionally coupled with the release of a second. These results suggest that LBP
      acts as a lipid exchange protein.

PMID- 9005997
TI  - Potentiation of beta-adrenergic signaling by adenoviral-mediated gene transfer in
      adult rabbit ventricular myocytes.
AB  - Our laboratory has been testing the hypothesis that genetic modulation of the
      beta-adrenergic signaling cascade can enhance cardiac function. We have
      previously shown that transgenic mice with cardiac overexpression of either the
      human beta2-adrenergic receptor (beta2AR) or an inhibitor of the beta-adrenergic
      receptor kinase (betaARK), an enzyme that phosphorylates and uncouples agonist
      bound receptors, have increased myocardial inotropy. We now have created
      recombinant adenoviruses encoding either the beta2AR (Adeno-beta2AR) or a peptide
      betaARK inhibitor (consisting of the carboxyl terminus of betaARK1, Adeno
      betaARKct) and tested their ability to potentiate beta-adrenergic signaling in
      cultured adult rabbit ventricular myocytes. As assessed by radioligand binding,
      Adeno-beta2AR infection led to approximately 20-fold overexpression of beta
      adrenergic receptors. Protein immunoblots demonstrated the presence of the Adeno
      betaARKct transgene. Both transgenes significantly increased isoproterenol
      stimulated cAMP as compared to myocytes infected with an adenovirus encoding beta
      galactosidase (Adeno-betaGal) but did not affect the sarcolemmal adenylyl cyclase
      response to Forskolin or NaF. beta-Adrenergic agonist-induced desensitization was
      significantly inhibited in Adeno-betaARKct-infected myocytes (16+/-2%) as
      compared to Adeno-betaGal-infected myocytes (37+/-1%, P < 0.001). We conclude
      that recombinant adenoviral gene transfer of the beta2AR or an inhibitor of
      betaARK-mediated desensitization can potentiate beta-adrenergic signaling.

PMID- 9006001
TI  - Acute bacterial pneumonia in rats increases alveolar epithelial fluid clearance
      by a tumor necrosis factor-alpha-dependent mechanism.
AB  - To study the rate and regulation of alveolar fluid clearance in acute pneumonia,
      we created a model of Pseudomonas aeruginosa pneumonia in rats. To measure
      alveolar liquid and protein clearance, we instilled into the airspaces a 5%
      bovine albumin solution with 1.5 microCi of 125I-human albumin, 24 h after
      intratracheal instillation of bacteria. The concentration of unlabeled and
      labeled protein in the distal airspaces over 1 h was used as an index of net
      alveolar fluid clearance. Since there was histologic evidence of alveolar
      epithelial injury, several methods were used to measure alveolar fluid clearance,
      including the use of experiments in rats with blood flow and the use of
      experiments in rats without blood flow, so that movement across the epithelial
      barrier would be minimized in the latter group. The results with each method were
      identical. We found that P. aeruginosa pneumonia increased alveolar liquid
      clearance over 1 h by 48% in studies with blood flow, and by 43% in rats without
      blood flow, compared with respective controls (P < 0.05). In both studies, this
      increase was inhibited with amiloride. However, propranolol had no inhibitory
      effect, thus ruling out a catecholamine-dependent mechanism to explain the
      increase in alveolar fluid clearance. An antitumor necrosis factor-alpha
      neutralizing antibody, instilled into the lung 5 min before bacteria, prevented
      the increase in alveolar liquid clearance in rats with pneumonia (P < 0.05).
      Also, TNFalpha (5 microg) instilled in normal rats increased alveolar liquid
      clearance by 43% over 1 h compared with control rats (P < 0.05). In normal rats
      instilled with TNFalpha, propranolol had no inhibitory effect. In conclusion,
      gram-negative pneumonia markedly upregulates net alveolar epithelial fluid
      clearance, in part by a TNFalpha-dependent mechanism. This finding provides a
      novel mechanism for the upregulation of alveolar epithelial sodium and fluid
      transport from the distal airspaces of the lung.

PMID- 9006002
TI  - Interferon-gamma differentially regulates interleukin-12 and interleukin-10
      production in leprosy.
AB  - The ability of monocytes to influence the nature of the T cell response to
      microbial pathogens is mediated in part by the release of cytokines. Of
      particular importance is the release of IL-12 and IL-10 by cells of the
      monocyte/macrophage lineage upon encountering the infectious agent. IL-12
      promotes cell mediated immunity (CMI) to intracellular pathogens by augmenting T
      helper type 1 responses, whereas IL-10 downregulates these responses. The ability
      of IFN-gamma to modulate the balance between IL-12 and IL-10 production was
      examined by studying leprosy as a model. In response to Mycobacterium leprae
      stimulation, IFN-gamma differentially regulated IL-12 and IL-10 production
      resulting in upregulation of IL-12 release and downregulation of IL-10 release.
      Furthermore, we determined that the mechanism by which IFN-gamma downregulates IL
      10 was through the induction of IL-12. The data suggest a model of lymphocyte
      monocyte interaction whereby the relative presence or absence of IFN-gamma in the
      local microenvironment is a key determinant of the type of monocyte cytokine
      response, and hence the degree of CMI in the host response to infection.

PMID- 9006003
TI  - Podocyte loss and progressive glomerular injury in type II diabetes.
AB  - Kidney biopsies from Pima Indians with type II diabetes were analyzed. Subjects
      were classified clinically as having early diabetes (n = 10), microalbuminuria (n
      = 17), normoalbuminuria, despite a duration of diabetes equal to that of the
      subjects with microalbuminuria (n = 12), or clinical nephropathy (n = 12).
      Subjects with microalbuminuria exhibited moderate increases in glomerular and
      mesangial volume when compared with those with early diabetes, but could not be
      distinguished from subjects who remained normoalbuminuric after an equal duration
      of diabetes. Subjects with clinical nephropathy exhibited global glomerular
      sclerosis and more prominent structural abnormalities in nonsclerosed glomeruli.
      Marked mesangial expansion was accompanied by a further increase in total
      glomerular volume. Glomerular capillary surface area remained stable, but the
      glomerular basement membrane thickness was increased and podocyte foot processes
      were broadened. Broadening of podocyte foot processes was associated with a
      reduction in the number of podocytes per glomerulus and an increase in the
      surface area covered by remaining podocytes. These findings suggest that podocyte
      loss contributes to the progression of diabetic nephropathy.

PMID- 9006006
TI  - Expression and characterization of DrrA and DrrB proteins of Streptomyces
      peucetius in Escherichia coli: DrrA is an ATP binding protein.
AB  - Streptomyces peucetius, a microorganism that produces the anticancer drugs
      doxorubicin and daunorubicin, is itself resistant to the action of these drugs.
      The genes conferring resistance to doxorubicin and daunorubicin in S. peucetius
      have been sequenced (P. G. Guilfoile and R. Hutchinson, Proc. Natl. Acad. Sci.
      USA 88:8553-8557, 1991). Two open reading frames, drrA and drrB, were proposed to
      encode for an ABC (ATP-binding cassette) type of permease that carries out export
      of the antibiotics in an ATP-dependent manner. This article reports subcloning of
      the drrA and drrB genes into Escherichia coli expression vectors and
      characterization of their gene products. Upon induction from the lac promoter, a
      36-kDa DrrA protein could be identified on Coomassie blue-stained gels. The DrrB
      protein was identified by use of a polyclonal antiserum generated against a
      synthetic peptide corresponding to a portion of the DrrB protein. Together, the
      DrrA and DrrB proteins conferred resistance to doxorubicin in E. coli. The DrrB
      protein was localized to the cell membrane. The DrrA protein bound ATP or GTP in
      a Mg2+-dependent fashion. ATP binding was enhanced on addition of doxorubicin or
      daunorubicin.

PMID- 9006005
TI  - Local ventromedial hypothalamus glucose perfusion blocks counterregulation during
      systemic hypoglycemia in awake rats.
AB  - The ventromedial hypothalamic nucleus (VMH) is necessary for the integrated
      hormonal response to hypoglycemia. To determine the role of the VMH as a glucose
      sensor, we performed experiments designed to specifically prevent glucopenia in
      the VMH, while producing hypoglycemia elsewhere. We used awake chronically
      catheterized rats, in which local VMH glucose perfusion (100 mM or 15 mM of D
      glucose) was combined with a sequential euglycemic-hypoglycemic clamp. In two
      control groups the VMH was perfused either with (a) an iso-osmotic solution
      lacking glucose, or with (b) nonmetabolizable L-glucose (100 mM). During systemic
      hypoglycemia glucagon and catecholamine concentrations promptly increased in the
      control animals perfused with either 100 mM L-glucose or the iso-osmotic solution
      lacking glucose. In contrast, glucagon, epinephrine and norepinephrine release
      was inhibited in the animals in which the VMH was perfused with D-glucose;
      hormonal secretion was partially suppressed by the VMH perfusion with 15 mM D
      glucose and suppressed by approximately 85% when the VMH was perfused with 100 mM
      D-glucose, as compared with the control groups. We conclude that the VMH must
      sense hypoglycemia for full activation of catecholamine and glucagon secretion
      and that it is a key glucose sensor for hypoglycemic counterregulation.

PMID- 9006004
TI  - Synergistic decrease of clonal proliferation, induction of differentiation, and
      apoptosis of acute promyelocytic leukemia cells after combined treatment with
      novel 20-epi vitamin D3 analogs and 9-cis retinoic acid.
AB  - Patients with acute promyelocytic leukemia (APL) usually relapse after all-trans
      retinoic acid (RA) treatment because this therapy fails to eradicate the
      malignant clone. Our data showed that KH 1060 and other 20-epi vitamin D3 analogs
      alone were potent inhibitors of clonal growth of NB4 cells, an APL cell line
      (ED50, approximately 5 x 10(-11) M). The combination of KH 1060 and 9-cis-RA
      synergistically and irreversibly enhanced this effect. Neither KH 1060 nor 9-cis
      RA (10(-6) M, 3 d) were strong inducers of differentiation of NB4 cells. However,
      98% of the cells underwent differentiation to a mature phenotype with features of
      both granulocytes and monocytes after exposure to a combination of both
      compounds. Apoptosis only increased after incubation of NB4 cells with 9-cis-RA
      alone (28%) or with a combination of 9-cis-RA plus KH1060 (32%).
      Immunohistochemistry showed that the bcl-2 protein decreased from nearly 100% of
      the wild-type NB4 cells to 2% after incubation with a combination of KH 1060 and
      9-cis-RA, and the bax protein increased from 50% of wild-type NB4 cells to 92%
      after culture with both analogs (5 x 10(-7) M, 3 d). Western blot analysis
      paralleled these results. Studies of APL cells from one untreated individual
      paralleled our results with NB4 cells. Taken together, the data demonstrated that
      nearly all of the NB4 cells can be irreversibly induced to differentiate
      terminally when exposed to the combination of KH 1060 and 9-cis-RA.

PMID- 9006007
TI  - Barriers to heterologous expression of a selenoprotein gene in bacteria.
AB  - The specificity parameters counteracting the heterologous expression in
      Escherichia coli of the Desulfomicrobium baculatum gene (hydV) coding for the
      large subunit of the periplasmic hydrogenase which is a selenoprotein have been
      studied. hydV'-'lacZ fusions were constructed, and it was shown that they do not
      direct the incorporation of selenocysteine in E. coli. Rather, the UGA codon is
      efficiently suppressed by some other aminoacyl-tRNA in an E. coli strain
      possessing a ribosomal ambiguity mutation. The suppression is decreased by the
      strA1 allele, indicating that the hydV selenocysteine UGA codon has the
      properties of a "normal" and suppressible nonsense codon. The SelB protein from
      D. baculatum was purified; in gel shift experiments, D. baculatum SelB displayed
      a lower affinity for the E. coli fdhF selenoprotein mRNA than E. coli SelB did
      and vice versa. Coexpression of the hydV'-'lacZ fusion and of the selB and
      tRNA(Sec) genes from D. baculatum, however, did not lead to selenocysteine
      insertion into the protein, although the formation of the quaternary complex
      between SelB, selenocysteyl-tRNA(Sec), and the hydV mRNA recognition sequence
      took place. The results demonstrate (i) that the selenocysteine-specific UGA
      codon is readily suppressed under conditions where the homologous SelB protein is
      absent and (ii) that apart from the specificity of the SelB-mRNA interaction, a
      structural compatibility of the quaternary complex with the ribosome is required.

PMID- 9006008
TI  - Characterization of membrane and protein interaction determinants of the
      Agrobacterium tumefaciens VirB11 ATPase.
AB  - The VirB11 ATPase is a putative component of the transport machinery responsible
      for directing the export of nucleoprotein particles (T complexes) across the
      Agrobacterium tumefaciens envelope to susceptible plant cells. Fractionation and
      membrane treatment studies showed that approximately 30% of VirB11 partitioned as
      soluble protein, whereas the remaining protein was only partially solubilized
      with urea from cytoplasmic membranes of wild-type strain A348 as well as a Ti
      plasmidless strain expressing virB11 from an IncP replicon. Mutations in virB11
      affecting protein function were mapped near the amino terminus (Q6L, P13L, and
      E25G), just upstream of a region encoding a Walker A nucleotide-binding site
      (F154H;L155M), and within the Walker A motif (P170L, K175Q, and delta GKT174
      176). The K175Q and delta GKT174-176 mutant proteins partitioned almost
      exclusively with the cytoplasmic membrane, suggesting that an activity associated
      with nucleotide binding could modulate the affinity of VirB11 for the cytoplasmic
      membrane. The virB11F154H;L155M allele was transdominant over wild-type virB11 in
      a merodiploid assay, providing strong evidence that at least one form of VirB11
      functions as a homo- or heteromultimer. An allele with a deletion of the first
      half of the gene, virB11 delta1-156, was transdominant in a merodiploid assay,
      indicating that the C-terminal half of VirB11 contains a protein interaction
      domain. Products of both virB11 delta1-156 and virB11 delta158-343, which
      synthesizes the N-terminal half of VirB11, associated tightly with the A.
      tumefaciens membrane, suggesting that both halves of VirB11 contain membrane
      interaction determinants.

PMID- 9006009
TI  - Isolation and characterization of a xylose-dependent promoter from Caulobacter
      crescentus.
AB  - An inducible promoter is a useful tool for the controlled expression of a given
      gene. Accordingly, we identified, cloned, and sequenced a chromosomal locus,
      xylX, from Caulobacter crescentus which is required for growth on xylose as the
      sole carbon source and showed that transcription from a single site is dependent
      on the presence of xylose in the growth medium. P(xylX) promoter activity was
      determined as a function of the composition of the growth medium both in single
      copy and on a plasmid using different reporter genes. One hundred micromolar
      exogenously added xylose was required for maximal induction of P(xylX) in a
      strain that is unable to metabolize xylose. P(xylX) activity was induced
      immediately after the addition of xylose and repressed almost completely when
      xylose was removed from the growth medium. In addition to the strong
      transcriptional control, the expression of xylX is also regulated on the
      translational level.

PMID- 9006010
TI  - Linker mutagenesis of the Caulobacter crescentus S-layer protein: toward a
      definition of an N-terminal anchoring region and a C-terminal secretion signal
      and the potential for heterologous protein secretion.
AB  - Linker insertion mutagenesis was used to modify the paracrystalline surface layer
      (S-layer) protein (RsaA) of the gram-negative bacterium Caulobacter crescentus.
      Eleven unique BamHI linker insertions in the cloned rsaA gene were identified; at
      the protein level, these linker insertions introduced 4 to 6 amino acids at
      positions ranging from the extreme N terminus to the extreme C terminus of the
      1,026-amino-acid RsaA protein. All linker-peptide insertions in the RsaA N
      terminus caused the secreted protein to be shed into the growth medium,
      suggesting that the RsaA N terminus is involved in cell surface anchoring. One
      linker-peptide insertion in the RsaA C terminus (amino acid 784) had no effect on
      S-layer biogenesis, while another (amino acid 907) disrupted secretion of the
      protein, suggesting that RsaA possesses a secretion signal lying C terminal to
      amino acid 784, near or including amino acid 907. Unlike extreme N- or C-terminal
      linker-peptide insertions, those more centrally located in the RsaA primary
      sequence had no apparent effect on S-layer biogenesis. By using a newly
      introduced linker-encoded restriction site, a 3' fragment of the rsaA gene
      encoding the last 242 C-terminal amino acids of the S-layer protein was expressed
      in C. crescentus from heterologous Escherichia coli lacZ transcription and
      translation initiation information. This C-terminal portion of RsaA was secreted
      into the growth medium, confirming the presence of a C-terminal secretion signal.
      The use of the RsaA C terminus for the secretion of heterologous proteins in C.
      crescentus was explored by fusing 109 amino acids of an envelope glycoprotein
      from infectious hematopoietic necrosis virus, a pathogen of salmonid fish, to the
      last 242 amino acids of the RsaA C terminus. The resulting hybrid protein was
      successfully secreted into the growth medium and accounted for 10% of total
      protein in a stationary-phase culture. Based on these results and features of the
      RsaA primary sequence, we propose that the C. crescentus S-layer protein is
      secreted by a type I secretion system, relying on a stable C-terminal secretion
      signal in a manner analogous to E. coli alpha-hemolysin, the first example of an
      S-layer protein secreted by such a pathway.

PMID- 9006011
TI  - Virulence and arsenic resistance in Yersiniae.
AB  - The genus Yersinia contains three pathogenic species: Yersinia pestis, Y.
      pseudotuberculosis, and Y. enterocolitica. Only a few biotypes and serotypes of
      Y. enterocolitica are pathogenic, and these form two distinct groups: some are of
      low virulence, and they are encountered worldwide; others, mainly encountered in
      North America, are markedly more virulent. All pathogenic yersiniae possess a 70
      kb virulence plasmid called pYV which encodes secreted antihost proteins called
      Yops as well as a type III secretion machinery that is required for Yop
      secretion. Genes encoding Yop synthesis and secretion are tightly clustered in
      three quadrants of the pYV plasmid. We show here that in the low-virulence
      strains of Y. enterocolitica, the fourth quadrant of the plasmid contains a new
      class II transposon, Tn2502. This transposon encodes a defective transposase, but
      transposition can be complemented in trans by Tn2501, another class II
      transposon. Tn2502 was not detected in the pYV plasmids of the more virulent
      American strains of Y. enterocolitica, of Y. pseudotuberculosis, and of Y.
      pestis. Tn2502 confers arsenite and arsenate resistance. This resistance involves
      four genes; three are homologous to the arsRBC genes present on the Escherichia
      coli chromosome, but no homolog of the fourth one, arsH, has been found. The
      systematic presence of such a resistance operon on a virulence plasmid is unusual
      and could be related to the recent spread of low-virulence Y. enterocolitica
      strains. The presence of this ars operon also constitutes the first significant
      difference between the pYV plasmids from different Yersinia species.

PMID- 9006012
TI  - Detection and comparison of specific hemin binding by Porphyromonas gingivalis
      and Prevotella intermedia.
AB  - A radioligand assay was designed to detect and compare specific hemin binding by
      the periodontal anaerobic black-pigmenting bacteria (BPB) Porphyromonas
      gingivalis and Prevotella intermedia. The assay included physiological
      concentrations of the hemin-binding protein rabbit serum albumin (RSA) to prevent
      self-aggregation and nonspecific interaction of hemin with cellular components.
      Under these conditions, heme-starved P. intermedia cells (two strains) expressed
      a single binding site species (4,100 to 4,600 sites/cell) with a dissociation
      constant (Kd) of 1.0 x 10(-9) M. Heme-starved P. gingivalis cells (two strains)
      expressed two binding site species; the higher-affinity site (1,000 to 1,500
      sites/cell) displayed a Kd of between 3.6 x 10(-11) and 9.6 x 10(-11) M, whereas
      the estimated Kd of the lower-affinity site (1.9 x 10(5) to 6.3 x 10(5)
      sites/cell) ranged between 2.6 x 10(-7) and 6.5 x 10(-8) M. Specific binding was
      greatly diminished in heme-replete cells of either BPB species and was not
      displayed by iron-replete Escherichia coli cells, which bound as much hemin in
      the absence of RSA as did P. intermedia. Hemin binding by BPB was reduced
      following treatment with protein-modifying agents (heat, pronase, and N
      bromosuccinimide) and was blocked by protoporphyrin IX and hemoglobin but not by
      Congo red. Hemopexin also inhibited bacterial hemin binding. These findings
      indicate that both P. gingivalis and P. intermedia express heme-repressible
      proteinaceous hemin-binding sites with affinities intermediate between those of
      serum albumin and hemopexin. P. gingivalis exhibited a 10-fold-greater specific
      binding affinity and greater heme storage capacity than did P. intermedia,
      suggesting that the former would be ecologically advantaged with respect to heme
      acquisition.

PMID- 9006013
TI  - bldA dependence of undecylprodigiosin production in Streptomyces coelicolor A3(2)
      involves a pathway-specific regulatory cascade.
AB  - The production of the red-pigmented tripyrrole antibiotic undecylprodigiosin
      (Red) by Streptomyces coelicolor A3(2) depends on two pathway-specific regulatory
      genes, redD and redZ. RedD is homologous to several other proteins that regulate
      antibiotic production in streptomycetes; RedZ is a member of the response
      regulator family. redZ transcripts were detected during exponential growth and
      increased in amount during transition and stationary phases; transcription of
      redD was confined to the two latter stages of growth. Whereas mutation of redD
      had no effect on redZ transcription, transcription of redD was highly dependent
      on redZ, suggesting that RedZ is a transcriptional activator of redD. bldA, which
      encodes the only tRNA of S. coelicolor that can efficiently translate the rare
      leucine codon UUA, is required for Red production at higher phosphate
      concentrations. While the redD transcript contains no UUA codons, the redZ mRNA
      contains one. Transcription of redZ appeared to be unaffected in a bldA mutant;
      in contrast, redD transcription was undetectable, consistent with the
      translational dependence of redZ on bldA and the transcriptional dependence of
      redD on redZ. Red production in a bldA mutant was restored by multiple copies of
      redZ, presumably reflecting a low level of mistranslation of the redZ UUA codon,
      while multiple copies of redD had no effect, presumably a consequence of the
      severe dependence of redD transcription on RedZ. Transcription of redZ appears to
      be negatively autoregulated.

PMID- 9006014
TI  - 4-hydroxybenzoyl coenzyme A reductase (dehydroxylating) is required for anaerobic
      degradation of 4-hydroxybenzoate by Rhodopseudomonas palustris and shares
      features with molybdenum-containing hydroxylases.
AB  - The anaerobic degradation of 4-hydroxybenzoate is initiated by the formation of 4
      hydroxybenzoyl coenzyme A, with the next step proposed to be a dehydroxylation to
      benzoyl coenzyme A, the starting compound for a central pathway of aromatic
      compound ring reduction and cleavage. Three open reading frames, divergently
      transcribed from the 4-hydroxybenzoate coenzyme A ligase gene, hbaA, were
      identified and sequenced from the phototrophic bacterium Rhodopseudomonas
      palustris. These genes, named hbaBCD, specify polypeptides of 17.5, 82.6, and
      34.5 kDa, respectively. The deduced amino acid sequences show considerable
      similarities to a group of hydroxylating enzymes involved in CO, xanthine, and
      nicotine metabolism that have conserved binding sites for [2Fe-2S] clusters and a
      molybdenum cofactor. Cassette disruption of the hbaB gene yielded a mutant that
      was unable to grow anaerobically on 4-hydroxybenzoate but grew normally on
      benzoate. The hbaB mutant cells did not accumulate [14C]benzoyl coenzyme A during
      short-term uptake of [14C]4-hydroxybenzoate, but benzoyl coenzyme A was the major
      radioactive metabolite formed by the wild type. In addition, crude extracts of
      the mutant failed to convert 4-hydroxybenzoyl coenzyme A to benzoyl coenzyme A.
      This evidence indicates that the hbaBCD genes encode the subunits of a 4
      hydroxybenzoyl coenzyme A reductase (dehydroxylating). The sizes of the specified
      polypeptides are similar to those reported for 4-hydroxybenzoyl coenzyme A
      reductase isolated from the denitrifying bacterium Thauera aromatica. The amino
      acid consensus sequence for a molybdenum cofactor binding site is in HbaC. This
      cofactor appears to be an essential component because anaerobic growth of R.
      palustris on 4-hydroxybenzoate, but not on benzoate, was retarded unless 0.1
      microM molybdate was added to the medium. Neither tungstate nor vanadate replaced
      molybdate, and tungstate competitively inhibited growth stimulation by molybdate.

PMID- 9006015
TI  - Characterization of four outer membrane proteins that play a role in utilization
      of starch by Bacteroides thetaiotaomicron.
AB  - Results of earlier work had suggested that utilization of polysaccharides by
      Bacteroides spp. did not proceed via breakdown by extracellular polysaccharide
      degrading enzymes. Rather, it appeared that the polysaccharide was first bound to
      a putative outer membrane receptor complex and then translocated into the
      periplasm, where the degradative enzymes were located. In a recent article, we
      reported the cloning and sequencing of susC, a gene from Bacteroides
      thetaiotaomicron that encoded a 115-kDa outer membrane protein. SusC protein
      proved to be essential for utilization not only of starch but also of
      intermediate-sized maltooligosaccharides (maltose to maltoheptaose). In this
      paper, we report the sequencing of a 7-kbp region of the B. thetaiotaomicron
      chromosome that lies immediately downstream of susC. We found four genes in this
      region (susD, susE, susF, and susG). Transcription of these genes was maltose
      inducible, and the genes appeared to be part of the same operon as susC. Western
      blot (immunoblot) analysis using antisera raised against proteins encoded by each
      of the four genes showed that all four were outer membrane proteins. Protein
      database searches revealed that SusE had limited similarity to a glucanohydrolase
      from Clostridium acetobutylicum and SusG had high similarity to amylases from a
      variety of sources. SusD and SusF had no significant similarity to any proteins
      in the databases. Results of 14C-starch binding assays suggested that SusD makes
      a major contribution to binding. SusE and SusF also appear to contribute to
      binding but not to the same extent as SusD. SusG is essential for growth on
      starch but appears to contribute little to starch binding. Our results
      demonstrate that the binding of starch to the B. thetaiotaomicron surface
      involves at least four outer membrane proteins (SusC, SusD, SusE, and SusF),
      which may form a surface receptor complex. The role of SusG in binding is still
      unclear.

PMID- 9006016
TI  - Role of the citrate pathway in glutamate biosynthesis by Streptococcus mutans.
AB  - In work previously reported (J. A. Gutierrez, P. J. Crowley, D. P. Brown, J. D.
      Hillman, P. Youngman, and A. S. Bleiweis, J. Bacteriol. 178:4166-4175, 1996), a
      Tn917 transposon-generated mutant of Streptococcus mutans JH1005 unable to
      synthesize glutamate anaerobically was isolated and the insertion point of the
      transposon was determined to be in the icd gene encoding isocitrate dehydrogenase
      (ICDH). The intact icd gene of S. mutans has now been isolated from an S. mutans
      genomic plasmid library by complementation of an icd mutation in Escherichia coli
      host strain EB106. Genetic analysis of the complementing plasmid pJG400 revealed
      an open reading frame (ORF) of 1,182 nucleotides which encoded an enzyme of 393
      amino acids with a predicted molecular mass of 43 kDa. The nucleotide sequence
      contained regions of high (60 to 72%) homology with icd genes from three other
      bacterial species. Immediately 5' of the icd gene, we discovered an ORF of 1,119
      nucleotides in length, designated citZ, encoding a homolog of known citrate
      synthase genes from other bacteria. This ORF encoded a predicted protein of 372
      amino acids with a molecular mass of 43 kDa. Furthermore, plasmid pJG400 was also
      able to complement a citrate synthase (gltA) mutation of E. coli W620. The enzyme
      activities of both ICDH, found to be NAD+ dependent, and citrate synthase were
      measured in cell extracts of wild-type S. mutans and E. coli mutants harboring
      plasmid pJG400. The region 5' from the citZ gene also revealed a partial ORF
      encoding 264 carboxy-terminal amino acids of a putative aconitase gene. The
      genetic and biochemical evidence indicates that S. mutans possesses the enzymes
      required to convert acetyl coenzyme A and oxalacetate to alpha-ketoglutarate,
      which is necessary for the synthesis of glutamic acid. Indeed, S. mutans JH1005
      was shown to assimilate ammonia as a sole source of nitrogen in minimal medium
      devoid of organic nitrogen sources.

PMID- 9006017
TI  - Mutations that increase expression of the rpoS gene and decrease its dependence
      on hfq function in Salmonella typhimurium.
AB  - The RpoS transcription factor (also called sigmaS or sigma38) is required for the
      expression of a number of stationary-phase and osmotically inducible genes in
      enteric bacteria. RpoS is also a virulence factor for several pathogenic species,
      including Salmonella typhimurium. The activity of RpoS is regulated in response
      to many different signals, at the levels of both synthesis and proteolysis.
      Previous work with rpoS-lac protein fusions has suggested that translation of
      rpoS requires hfq function. The product of the hfq gene, host factor I (HF-I), is
      a ribosome-associated, site-specific RNA-binding protein originally characterized
      for its role in replication of the RNA bacteriophage Qbeta of Escherichia coli.
      In this study, the role of HF-I was explored by isolating suppressor mutations
      that map to the region directly upstream of rpoS. These mutations increase rpoS
      lac expression in the absence of HF-I and also confer substantial independence
      from HF-I. DNA sequence analysis of the mutants suggests a model in which the RNA
      secondary structure near the ribosome binding site of the rpoS mRNA plays an
      important role in limiting expression in the wild type. Genetic tests of the
      model confirm its predictions, at least in part. It seems likely that the
      mutations analyzed here activate a suppression pathway that bypasses the normal
      HF-I-dependent route of rpoS expression; however, it is also possible that some
      of them identify a sequence element with an inhibitory function that is directly
      counteracted by HF-I.

PMID- 9006018
TI  - Analysis of the cbbXYZ operon in Rhodobacter sphaeroides.
AB  - Three genes, cbbX, cbbY, and cbbZ were found downstream from the form I ribulose
      1,5-bisphosphate carboxylase/oxygenase (RubisCO) genes of Rhodobacter
      sphaeroides. As in chemoautotrophic bacteria, cbbZ was shown to encode
      phosphoglycolate phosphatase (PGP), whereas the identities of cbbX and cbbY are
      not known. To determine the physiological function of the cbbXYZ gene products,
      we constructed R. sphaeroides strains in which the genes were inactivated and
      characterized the resultant mutant strains according to growth phenotype and
      levels of RubisCO and PGP. Only a mutation in cbbX resulted in a discernible
      phenotype, namely, impaired photoautotrophic growth. No PGP activity was observed
      in any of the mutants, suggesting that the three genes are transcriptionally
      linked. Studies with a spontaneous chemoautotrophic competent derivative of the
      CBBX mutant suggested that the cbbXYZ gene products are not essential for
      chemoautotrophic growth. PGP activity determined in the wild-type strain grown
      under a variety of growth conditions, and in various strains containing mutations
      in Calvin-Benson-Bassham cycle structural and regulatory genes, indicated that
      transcription of the cbb(I) operon influenced expression of the downstream cbbXYZ
      operon.

PMID- 9006019
TI  - Anaerobic activation of toluene and o-xylene by addition to fumarate in
      denitrifying strain T.
AB  - Anaerobic assays conducted with strain T, a denitrifying bacterium capable of
      mineralizing toluene to carbon dioxide, demonstrated that toluene-grown,
      permeabilized cells catalyzed the addition of toluene to fumarate to form
      benzylsuccinate. This reaction was not dependent on the presence of coenzyme A
      (CoA) or ATP. In the presence of CoA, formation of E-phenylitaconate from
      benzylsuccinate was also observed. Kinetic studies demonstrated that the specific
      rate of benzylsuccinate formation from toluene and fumarate in assays with
      permeabilized cells was >30% of the specific rate of toluene consumption in whole
      cell suspensions with nitrate; this observation suggests that benzylsuccinate
      formation may be the first reaction in anaerobic toluene degradation by strain T.
      Use of deuterium-labeled toluene and gas chromatography-mass spectrometry
      indicated that the H atom abstracted from the toluene methyl group during
      addition to fumarate was retained in the succinyl moiety of benzylsuccinate. In
      this study, no evidence was found to support previously proposed reactions of
      toluene with acetyl-CoA or succinyl-CoA. Toluene-grown, permeabilized cells of
      strain T also catalyzed the addition of o-xylene to fumarate to form (2
      methylbenzyl)succinate. o-Xylene is not a growth substrate for strain T, and its
      transformation was probably cometabolic. With the exception of specific reaction
      rates, the observed characteristics of the toluene-fumarate addition reaction
      (i.e., retention of a methyl H atom and independence from CoA and ATP) also apply
      to the o-xylene-fumarate addition reaction. Thus, addition to fumarate may be a
      biochemical strategy to anaerobically activate a range of methylbenzenes.

PMID- 9006021
TI  - Binding of a novel host factor to the pT181 plasmid replication enhancer.
AB  - Replication enhancers are cis-acting genetic elements that stimulate the activity
      of origins of DNA replication. The enhancer found in plasmid pT181 of
      Staphylococcus aureus, called cmp, functions at a distance of 1 kb from the
      origin of DNA replication to stimulate the interaction between the replication
      initiation protein and the origin. DNA encoding cmp-binding activity was isolated
      by screening an expression library of S. aureus DNA in Escherichia coli, and a
      novel gene, designated cbf1, was identified. The cbf1 locus codes for a
      polypeptide of 313 amino acid residues (cmp-binding factor 1 [CBF1]; Mr =
      35,778). In its COOH-terminal region, the protein sequence contains the helix
      turn-helix motif common to many DNA binding proteins that usually bend DNA. The
      specificity of CBF1 binding for cmp was demonstrated by affinity chromatography
      using cmp DNA and by competition binding studies. DNase I footprinting analysis
      of the CBF1-cmp complexes revealed DNase I-hypersensitive sites in phase with the
      helical periodicity of DNA, implying that CBF1 increases distortion of the
      intrinsically bent cmp DNA.

PMID- 9006020
TI  - Secretion of nuclease across the outer membrane of Serratia marcescens and its
      energy requirements.
AB  - Extracellular secretion of Serratia marcescens nuclease occurs as a two-step
      process via a periplasmic intermediate. Unlike other extracellular proteins
      secreted by gram-negative bacteria by the general secretory pathway, nuclease
      accumulates in the periplasm in its active form for an unusually long time before
      its export into the growth medium. The energy requirements for extracellular
      secretion of nuclease from the periplasm were investigated. Our results suggest
      that the second step of secretion across the outer membrane is dependent upon the
      external pH; acidic pH effectively but reversibly blocks extracellular secretion.
      However, electrochemical proton gradient, and possibly ATP hydrolysis, are not
      required for this step. We suggest that nuclease uses a novel mechanism for the
      second step of secretion in S. marcescens.

PMID- 9006022
TI  - Characterization of in-frame proteins encoded by cvaA, an essential gene in the
      colicin V secretion system: CvaA* stabilizes CvaA to enhance secretion.
AB  - Colicin V (ColV), an antibacterial peptide toxin, uses a dedicated signal
      sequence-independent export system for its extracellular secretion in Escherichia
      coli. The products of at least three genes (a chromosomal tolC gene and two
      plasmid-born cvaA and cvaB genes) are involved in this process. To characterize
      the gene products, the cvaA gene was subcloned and expressed under the control of
      T7 RNA polymerase promoter. Two in-frame proteins, CvaA and CvaA*, were expressed
      and identified. DNA sequences predicted that both proteins have two potential
      translational initiation sites. N-terminal peptide sequencing showed that the
      translation of CvaA starts from a TTG, 11 amino acids upstream of the previously
      proposed ATG initiation site. CvaA* is translated from an upstream ATG.
      Expression of both CvaA and CvaA* was induced by the iron chelator 2,2'
      dipyridyl, indicating that cvaA is negatively regulated at least partially by
      Fur. CvaA*-depleted cells were found to secrete less ColV, based on reduced
      activity in the supernatant, than did wild type, which was recovered by the
      addition of a plasmid producing CvaA*. Interestingly, CvaA*-depleted and wild
      type cells had similar levels of intracellular ColV activity. Translational
      fusions showed that the syntheses of ColV and CvaA are not affected by CvaA*
      depletion. However, CvaA in CvaA*-depleted cells was less stable than that in
      wild-type cells, indicating that CvaA* may directly or indirectly affect the
      stability of CvaA. We conclude that CvaA* is not essential for ColV secretion but
      that it enhances the ColV secretion by stabilizing the CvaA protein.

PMID- 9006023
TI  - Purification of peptide synthetases involved in pristinamycin I biosynthesis.
AB  - Several assays of pristinamycin I synthetases based on adenylate or thioester
      formation were developed. Purification to near homogeneity of these enzymatic
      activities from cell extracts of Streptomyces pristinaespiralis showed that three
      enzymes could activate all pristinamycin I precursors. SnbA, a 3-hydroxypicolinic
      acid: AMP ligase activating the first pristinamycin I residue, was purified 200
      fold, using an ATP-pyrophosphate exchange assay. This enzyme was shown to be a
      monomer with an Mr of 67,000 as estimated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Then a multifunctional enzyme, consisting of
      two identical subunits (SnbC) with Mrs of 240,000 and able to bind covalently L
      threonine as a thioester, was purified 100-fold. This protein also activated L
      aminobutyric acid, which is further epimerized to generate the third residue of
      the pristinamycin I macrocycle. A third protein, consisting of two identical
      subunits (SnbD) with Mrs estimated to be between 250,000 and 350,000, was
      purified 200-fold. This large enzyme catalyzed thioesterification and subsequent
      N-methylation of 4-dimethylamino-L-phenylalanine, the fifth pristinamycin I
      residue. SnbD could also activate L-proline, the fourth pristinamycin I residue,
      and some preparations retained a low but significant activity for the last two
      pristinamycin I precursors. Finally, a single polypeptide chain (SnbE) with an Mr
      of 170,000, catalyzing L-phenylglycine-dependent ATP-pyrophosphate exchange, was
      purified 3,000-fold and characterized. Stepwise Edman degradation of the entire
      polypeptides or some of their internal fragments provided amino acid sequences
      for the four isolated proteins. The purified SnbE protein was further shown to be
      a proteolytic fragment of SnbD.

PMID- 9006025
TI  - The ggtA gene encodes a subunit of the transport system for the osmoprotective
      compound glucosylglycerol in Synechocystis sp. strain PCC 6803.
AB  - The ggtA gene was sequenced during the analysis of a mutant of Synechocystis sp.
      strain PCC 6803 with impaired salt tolerance. It showed striking sequence
      similarities to ATP-binding proteins of binding-protein-dependent transport
      systems (ABC transporters). Mutants of ggtA and three neighboring reading frames
      were constructed by inserting an aphII gene cassette and were physiologically and
      genetically characterized. The ggtA insertion mutant lost its glucosylglycerol
      (GG) uptake ability, but its salt tolerance did not change. Therefore, it was
      concluded that active transport of the osmoprotective compound GG in
      Synechocystis is mediated by an ABC transporter. The genes for the GG-specific
      ABC transporter are not organized in an operon as usually found for comparable
      transporters, since the other insertion mutants showed normal GG transport
      activity. After cultivation of the ggtA mutant at high salt concentrations,
      significant amounts of GG were found in the cultivation medium, indicating that
      GG transport is mainly necessary for recovery of GG leaked through the
      cytoplasmic membrane. The Northern blot technique revealed increased
      transcription of the ggtA gene in cells adapted to higher salt concentrations,
      whereas in cells from basal medium, its transcription was weak.

PMID- 9006024
TI  - Pristinamycin I biosynthesis in Streptomyces pristinaespiralis: molecular
      characterization of the first two structural peptide synthetase genes.
AB  - Two genes involved in the biosynthesis of the depsipeptide antibiotics
      pristinamycins I (PI) produced by Streptomyces pristinaespiralis were cloned and
      sequenced. The 1.7-kb snbA gene encodes a 3-hydroxypicolinic acid:AMP ligase, and
      the 7.7-kb snbC gene encodes PI synthetase 2, responsible for incorporating L
      threonine and L-aminobutyric acid in the PI macrocycle. snbA and snbC, which
      encode the two first structural enzymes of PI synthesis, are not contiguous. Both
      genes are located in PI-specific transcriptional units, as disruption of one gene
      or the other led to PI-deficient strains producing normal levels of the
      polyunsaturated macrolactone antibiotic pristinamycin II, also produced by S.
      pristinaespiralis. Analysis of the deduced amino acid sequences showed that the
      SnbA protein is a member of the adenylate-forming enzyme superfamily and that the
      SnbC protein contains two amino acid-incorporating modules and a C-terminal
      epimerization domain. A model for the initiation of PI synthesis analogous to the
      established model of initiation of fatty acid synthesis is proposed.

PMID- 9006027
TI  - Oxidative inactivation of glutamine synthetase from the cyanobacterium Anabaena
      variabilis.
AB  - In crude extracts of the cyanobacterium Anabaena variabilis, glutamine synthetase
      (GS) could be effectively inactivated by the addition of NADH. GS inactivation
      was completed within 30 min. Both the inactivated GS and the active enzyme were
      isolated. No difference between the two enzyme forms was seen in sodium dodecyl
      sulfate-gels, and only minor differences were detectable by UV spectra, which
      excludes modification by a nucleotide. Mass spectrometry revealed that the
      molecular masses of active and inactive GS are equal. While the Km values of the
      substrates were unchanged, the Vmax values of the inactive GS were lower,
      reflecting the inactivation factor in the crude extract. This result indicates
      that the active site was affected. From the crude extract, a fraction mediating
      GS inactivation could be enriched by ammonium sulfate precipitation and gel
      filtration. GS inactivation by this fraction required the presence of NAD(P)H,
      Fe3+, and oxygen. In the absence of the GS-inactivating fraction, GS could be
      inactivated by Fe2+ and H2O2. The GS-inactivating fraction produced Fe2+ and
      H2O2, using NADPH, Fe3+, and oxygen. Accordingly, the inactivating fraction was
      inhibited by catalase and EDTA. This GS-inactivating system of Anabaena is
      similar to that described for oxidative GS inactivation in Escherichia coli. We
      conclude that GS inactivation by NAD(P)H is caused by irreversible oxidative
      damage and is not due to a regulatory mechanism of nitrogen assimilation.

PMID- 9006026
TI  - Nitrate- and nitrite-sensing protein NarX of Escherichia coli K-12: mutational
      analysis of the amino-terminal tail and first transmembrane segment.
AB  - Nitrate and nitrite control of anaerobic respiratory gene expression is mediated
      by dual two-component regulatory systems. The sensors NarX and NarQ each
      communicate nitrate and nitrite availability to the response regulators NarL and
      NarP. In the presence of nitrate, the NarX protein acts as a positive regulator
      ("kinase") of both NarL and NarP activity. In the presence of nitrite, the NarX
      protein acts primarily as a negative regulator ("phosphatase") of NarL activity
      but remains a positive regulator of NarP activity. In other topologically similar
      sensory proteins, such as the methyl-accepting chemotaxis proteins, the
      transmembrane regions are important for signal transduction. We therefore used
      localized mutagenesis of the amino-terminal coding region to isolate mutations in
      narX that confer an altered signaling phenotype. Five of the mutations studied
      alter residues in the amino-terminal cytoplasmic tail, and five alter residues in
      the first transmembrane segment. Based on patterns of target operon expression in
      various regulatory mutant strain backgrounds, most of the mutant NarX proteins
      appear to have alterations in negative control function. One mutant, with a
      change of residue Leu-11 to Pro in the cytoplasmic tail, exhibits strikingly
      altered patterns of NarL- and NarP-dependent gene expression. We conclude that
      the amino terminus of the NarX protein is important for the differential response
      to nitrate and nitrite.

PMID- 9006028
TI  - Role of conserved residues in hydrophilic loop 8-9 of the lactose permease.
AB  - A peptide motif, GXXX(D/E)(R/K)XG(R/K)(R/K), has been conserved in a large group
      of evolutionarily related membrane proteins that transport small molecules across
      the membrane. Within the superfamily, this motif is located in two cytoplasmic
      loops that connect transmembrane segments 2 and 3 and transmembrane segments 8
      and 9. In a previous study concerning the loop 2-3 motif of the lactose permease
      (A. E. Jessen-Marshall, N. J. Paul, and R. J. Brooker, J. Biol. Chem. 270:16251
      16257, 1995), it was shown that the first-position glycine and the fifth-position
      aspartate are critical for transport activity since a variety of site-directed
      mutations greatly diminished the rate of transport. In the current study, a
      similar approach was used to investigate the functional significance of the
      conserved residues in the loop 8-9 motif. In the wild-type lactose permease,
      however, this motif has been evolutionarily modified so that the first-position
      glycine (an alpha-helix breaker) has been changed to proline (also a helix
      breaker); the fifth position has been changed to an asparagine; and one of the
      basic residues has been altered. In this investigation, we made a total of 28
      single and 7 double mutants within the loop 8-9 motif to explore the functional
      importance of this loop. With regard to transport activity, amino acid
      substitutions within the loop 8-9 motif tend to be fairly well tolerated. Most
      substitutions produced permeases with normal or mildly defective transport
      activities. However, three substitutions at the first position (i.e., position
      280) resulted in defective lactose transport. Kinetic analysis of position 280
      mutants indicated that the defect decreased the Vmax for lactose uptake. Besides
      substitutions at position 280, a Gly-288-to-Thr mutant had the interesting
      property that the kinetic parameters for lactose uptake were normal yet the rates
      of lactose efflux and exchange were approximately 10-fold faster than wild-type
      rates. The results of this study suggest that loop 8-9 may facilitate
      conformational changes that translocate lactose.

PMID- 9006029
TI  - Importance of structural differences between complementary RNA molecules to
      control of replication of an IncB plasmid.
AB  - Replication of the IncB miniplasmid pMU720 is dependent on the expression of
      repA, the gene encoding replication initiator protein RepA. Binding of a small
      antisense RNA (RNAI) to its complementary target (stem-loop I [SLI]) in the RepA
      mRNA prevents the participation of SLI in the formation of a pseudoknot that is
      an enhancer of translation of this mRNA. Thus, RNAI regulates the frequency of
      replication of pMU720 by controlling the efficiency of translation of the RepA
      mRNA. Mutational analysis of the two seven-base complementary sequences involved
      in formation of the pseudoknot showed that only the five central bases of each
      were critical for the formation of the pseudoknot. Physical analysis of SLI
      showed that despite the complete complementarity of its sequence to that of RNAI,
      the structures of the two molecules are different. The most prominent difference
      between the two structures is the presence of a 4-base internal loop immediately
      below the hairpin loop of SLI but not that of RNAI. Closure of this internal loop
      in SLI resulted in a 40-fold reduction in repA expression and loss of sensitivity
      of the residual expression to inhibition by RNAI. By contrast, repA expression
      was largely unaffected by the closure of a lower internal loop whose presence in
      SLI and RNAI is essential for effective interaction between these two molecules.
      These results suggest that the interaction of SLI with the distal pseudoknot
      bases is fundamentally different from the RNAI-SLI binding interaction and that
      the differences in structure between RNAI and SLI are necessary to allow SLI to
      be able to efficiently bind RNAI and to participate in pseudoknot formation.

PMID- 9006031
TI  - Determinants for overproduction of the Pseudomonas oleovorans cytoplasmic
      membrane protein alkane hydroxylase in alk+ Escherichia coli W3110.
AB  - The Pseudomonas oleovorans alkB gene is expressed in alk+ Escherichia coli W3110
      to 10 to 15% of the total cell protein, which is exceptional for a (foreign)
      cytoplasmic membrane protein. In other E. coli recombinants such as alk+ HB101,
      AlkB constitutes 2 to 3% of the total protein. In this study, we have
      investigated which factors determine the expression level of alkB in alk+ W3110.
      In particular, we have investigated the role of AlkB-induced stimulation of
      phospholipid synthesis. Blocking phospholipid synthesis in alk+ W3110 did not
      specifically alter the expression of alkB, and we conclude that stimulation of
      phospholipid synthesis is not a prerequisite for high-level expression of the
      membrane protein. W3110 is able to produce exceptionally high levels of alkane
      monooxygenase, because the rate of alkB mRNA synthesis in W3110 is an order of
      magnitude higher than that in HB101. This may be due in part to the higher copy
      number of pGEc47 in W3110 in comparison with HB101.

PMID- 9006030
TI  - Apparent and real recombination frequencies in multicopy plasmids: the need for a
      novel approach in frequency determination.
AB  - Recombination studies of bacteria are often carried out with multicopy plasmids,
      and recombination frequencies are often deduced from the proportion of cells in
      the population that express a recombinant phenotype. These frequencies should
      however be called apparent frequencies, since detection of the recombinant cells
      requires not only the formation of a rearranged plasmid but also its
      establishment in the cell. The establishment of the recombinant plasmid can
      possibly be affected by its interaction with the parental plasmids. To test this
      hypothesis, we have used a plasmid system enabling the study of deletion
      formation between short direct repeats (18 bp) in Bacillus subtilis and developed
      a method by which deletion frequencies are measured under conditions under which
      interaction is abolished. Real deletion frequencies were thus determined and
      compared with apparent deletion frequencies. Real frequencies were underestimated
      by a factor ranging from 4- to 500-fold, depending upon the plasmid under study.
      This implies that a large majority of the recombinant molecules that are formed
      are generally not detected. We show that apparent deletion frequencies strongly
      depend upon (i) the parental plasmid copy number, (ii) the ability of the
      recombinant molecules to form heterodimeric plasmids, and (iii) the fitness of
      the recombinant molecules relative to that of parental molecules. Finally, we
      show that under conditions under which all recombinant molecules are scored,
      transcription can inhibit the deletion process 10-fold.

PMID- 9006032
TI  - Identification and characterization of a gene encoding a vertebrate-type carbonic
      anhydrase in cyanobacteria.
AB  - A gene (designated ecaA) encoding a vertebrate-like (alpha-type) carbonic
      anhydrase (CA) has been isolated from two disparate cyanobacteria, Anabaena sp.
      strain PCC 7120 and Synechococcus sp. strain PCC 7942. The deduced amino acid
      sequences correspond to proteins of 29 and 26 kDa, respectively, and revealed
      significant sequence similarity to human CAI and CAII, as well as Chlamydomonas
      CAHI, including conservation of most active-site residues identified in the
      animal enzymes. Structural similarities between the animal and cyanobacterial
      enzymes extend to the levels of antigenicity, as the Anabaena protein cross
      reacts with antisera derived against chicken CAII. Expression of the
      cyanobacterial ecaA is regulated by CO2 concentration and is highest in cells
      grown at elevated levels of CO2. Immunogold localization using an antibody
      derived against the ecaA protein indicated an extracellular location. Preliminary
      analysis of Synechococcus mutants in which ecaA has been inactivated by insertion
      of a drug resistance cassette suggests that extracellular carbonic anhydrase
      plays a role in inorganic-carbon accumulation by maintaining equilibrium levels
      of CO2 and HCO3- in the periplasm.

PMID- 9006033
TI  - Lack of functional complementation between Bordetella pertussis filamentous
      hemagglutinin and Proteus mirabilis HpmA hemolysin secretion machineries.
AB  - The gram-negative bacterium Bordetella pertussis has adapted specific secretion
      machineries for each of its major secretory proteins. In particular, the highly
      efficient secretion of filamentous hemagglutinin (FHA) is mediated by the
      accessory protein FhaC. FhaC belongs to a family of outer membrane proteins which
      are involved in the secretion of large adhesins or in the activation and
      secretion of Ca2+-independent hemolysins by several gram-negative bacteria. FHA
      shares with these hemolysins a 115-residue-long amino-proximal region essential
      for its secretion. To compare the secretory pathways of these hemolysins and FHA,
      we attempted functional transcomplementation between FhaC and the Proteus
      mirabilis hemolysin accessory protein HpmB. HpmB could not promote the secretion
      of FHA derivatives. Likewise, FhaC proved to be unable to mediate secretion and
      activation of HpmA, the cognate secretory partner of HpmB. In contrast, ShlB, the
      accessory protein of the closely related Serratia marcescens hemolysin, was able
      to activate and secrete HpmA. Two invariant asparagine residues lying in the
      region of homology shared by secretory proteins and shown to be essential for the
      secretion and activation of the hemolysins were replaced in FHA by site-directed
      mutagenesis. Replacements of these residues indicated that both are involved in,
      but only the first one is crucial to, FHA secretion. This slight discrepancy
      together with the lack of functional complementation demonstrates major
      differences between the hemolysins and FHA secretion machineries.

PMID- 9006034
TI  - Two polypeptide products of the Escherichia coli cell division gene ftsW and a
      possible role for FtsW in FtsZ function.
AB  - Two new mutations in the cell division gene ftsW have been isolated and
      characterized. The ftsW263(Ts) mutation results in a block to division at the
      initiation stage, similar to that previously observed with the ftsW201(Ts)
      mutation. The ftsW1640(Ts) mutation, however, causes a block to division at a
      later stage. The ftsW201 and ftsW263 mutants were shown to be phenotypically
      sensitive to the genetic background and growth conditions and are possibly relA
      dependent. Immunofluorescence microscopy showed that the FtsZ protein can
      localize to presumptive division sites in strains carrying ftsW(Ts) mutations at
      the nonpermissive temperature, suggesting that FtsW is unlikely to be
      specifically required for the localization of FtsZ to the division site.
      Examination of the localization of FtsZ in an ftsW rodA double mutant (lemon
      shaped cells) revealed several classes of cells ranging from a common class where
      an FtsZ ring structure is absent to a class where FtsZ forms a complete ring at
      the midpoint of a lemon-shaped cell, suggesting a role for FtsW in the
      establishment of a stable FtsZ-based septal structure. We further demonstrate
      that two FtsW peptides, FtsWL (large) and FtsWS (small), can be identified and
      that the expression of ftsWS is sufficient for complementation of ftsW(Ts)
      mutations.

PMID- 9006036
TI  - Neisseria meningitidis tonB, exbB, and exbD genes: Ton-dependent utilization of
      protein-bound iron in Neisseriae.
AB  - We have recently cloned and characterized the hemoglobin (Hb) receptor gene,
      hmbR, from Neisseria meningitidis. To identify additional proteins that are
      involved in Hb utilization, the N. meningitidis Hb utilization system was
      reconstituted in Escherichia coli. Five cosmids from N. meningitidis DNA library
      enabled a heme-requiring (hemA), HmbR-expressing mutant of E. coli to use Hb as
      both porphyrin and iron source. Nucleotide sequence analysis of DNA fragments
      subcloned from the Hb-complementing cosmids identified four open reading frames,
      three of them homologous to Pseudomonas putida, E. coli, and Haemophilus
      influenzae exbB, exbD, and tonB genes. The N. meningitidis TonB protein is 28.8
      to 33.6% identical to other gram-negative TonB proteins, while the N.
      meningitidis ExbD protein shares between 23.3 and 34.3% identical amino acids
      with other ExbD and TolR proteins. The N. meningitidis ExbB protein was 24.7 to
      36.1% homologous with other gram-negative ExbB and TolQ proteins. Complementation
      studies indicated that the neisserial Ton system cannot interact with the E. coli
      FhuA TonB-dependent outer membrane receptor. The N. meningitidis tonB mutant was
      unable to use Hb, Hb-haptoglobin complexes, transferrin, and lactoferrin as iron
      sources. Insertion of an antibiotic cassette in the 3' end of the exbD gene
      produced a leaky phenotype. Efficient usage of heme by N. meningitidis tonB and
      exbD mutants suggests the existence of a Ton-independent heme utilization
      mechanism. E. coli complementation studies and the analysis of N. meningitidis
      hmbR and hpu mutants suggested the existence of another Hb utilization mechanism
      in this organism.

PMID- 9006035
TI  - Autodisplay: one-component system for efficient surface display and release of
      soluble recombinant proteins from Escherichia coli.
AB  - The immunoglobulin A protease family of secreted proteins are derived from self
      translocating polyprotein precursors which contain C-terminal domains promoting
      the translocation of the N-terminally attached passenger domains across gram
      negative bacterial outer membranes. Computer predictions identified the C
      terminal domain of the Escherichia coli adhesin involved in diffuse adherence
      (AIDA-I) as a member of the autotransporter family. A model of the beta-barrel
      structure, proposed to be responsible for outer membrane translocation, served as
      a basis for the construction of fusion proteins containing heterologous
      passengers. Autotransporter-mediated surface display (autodisplay) was
      investigated for the cholera toxin B subunit and the peptide antigen tag PEYFK.
      Up to 5% of total cellular protein was detectable in the outer membrane as
      passenger autotransporter fusion protein synthesized under control of the
      constitutive P(TK) promoter. Efficient presentation of the passenger domains was
      demonstrated in the outer membrane protease T-deficient (ompT) strain E. coli
      UT5600 and the ompT dsbA double mutant JK321. Surface exposure was ascertained by
      enzyme-linked immunosorbent assay, immunofluorescence microscopy, and immunogold
      electron microscopy using antisera specific for the passenger domains. In strain
      UT2300 (ompT+), the passenger domains were released from the cell surface by the
      OmpT protease at a novel specific cleavage site, R / V. Autodisplay represents a
      useful tool for future protein translocation studies with interesting
      biotechnological possibilities.

PMID- 9006037
TI  - Assembly of the switch complex onto the MS ring complex of Salmonella typhimurium
      does not require any other flagellar proteins.
AB  - The cytoplasmic portion of the bacterial flagellum is thought to consist of at
      least two structural components: a switch complex and an export apparatus. These
      components seem to assemble around the MS ring complex, which is the first
      flagellar basal body substructure and is located in the cytoplasmic membrane. In
      order to elucidate the process of assembly of cytoplasmic substructures, the
      membrane localization of each component of the switch complex (FliG, FliM, and
      FliN) in various nonflagellated mutants was examined by immunoblotting. It was
      found that all these switch proteins require the MS ring protein FliF to
      associate with the cell membrane. FliG does not require FliM and FliN for this
      association, but FliM and FliN associate cooperatively with the membrane only
      through FliG. Furthermore, all three switch proteins were detected in membranes
      isolated from fliE, fliH, fliI, fliJ, fliO, fliP, fliQ, fliR, flhA, flhB, and
      flgJ mutants, indicating that the switch complex assembles on the MS ring complex
      without any other flagellar proteins involved in the early stage of flagellar
      assembly. The relationship between the switch complex and the export apparatus is
      discussed.

PMID- 9006038
TI  - Molecular evolution and diversity in Bacillus anthracis as detected by amplified
      fragment length polymorphism markers.
AB  - Bacillus anthracis causes anthrax and represents one of the most molecularly
      monomorphic bacteria known. We have used AFLP (amplified fragment length
      polymorphism) DNA markers to analyze 78 B. anthracis isolates and six related
      Bacillus species for molecular variation. AFLP markers are extremely sensitive to
      even small sequence variation, using PCR and high-resolution electrophoresis to
      examine restriction fragments. Using this approach, we examined ca. 6.3% of the
      Bacillus genome for length mutations and ca. 0.36% for point mutations. Extensive
      variation was observed among taxa, and both cladistic and phenetic analyses were
      used to construct a phylogeny of B. anthracis and its closest relatives. This
      genome-wide analysis of 357 AFLP characters (polymorphic fragments) indicates
      that B. cereus and B. thuringiensis are the closest taxa to B. anthracis, with B.
      mycoides slightly more distant. B. subtilis, B. polymyxa, and B.
      stearothermophilus shared few AFLP markers with B. anthracis and were used as
      outgroups to root the analysis. In contrast to the variation among taxa, only
      rare AFLP marker variation was observed within B. anthracis, which may be the
      most genetically uniform bacterial species known. However, AFLP markers did
      establish the presence or absence of the pXO1 and pXO2 plasmids and detected 31
      polymorphic chromosomal regions among the 79 B. anthracis isolates. Cluster
      analysis identified two very distinct genetic lineages among the B. anthracis
      isolates. The level of variation and its geographic distribution are consistent
      with a historically recent African origin for this pathogenic organism. Based on
      AFLP marker similarity, the ongoing anthrax epidemic in Canada and the northern
      United States is due to a single strain introduction that has remained stable
      over at least 30 years and a 1,000-mile distribution.

PMID- 9006039
TI  - Genetic analysis of the catalytic domain of the chemotaxis-associated histidine
      kinase CheA.
AB  - Escherichia coli cells express two forms of CheA, the histidine kinase associated
      with chemotaxis. The long form, CheA(L), plays a critical role in chemotactic
      signal transduction by phosphorylating two chemotaxis-associated response
      regulators, CheY and CheB. CheA(L) first autophosphorylates amino acid His-48
      before its phosphoryl group is transferred to these response regulators. The
      short form, CheA(S), lacks the amino-terminal 97 amino acids of CheA(L) and
      therefore does not possess the site of phosphorylation. The centrally located
      transmitter domain of both forms of CheA contains four regions, called N, G1, F,
      and G2, highly conserved among histidine kinases of the family of two-component
      signal transduction systems. On the basis of sequence similarity to highly
      conserved regions of certain eukaryotic kinases, the G1 and G2 regions are
      purported to be involved in the binding and hydrolysis of ATP. We report here
      that alleles mutated in the G1, G2, or F region synthesize CheA variants that
      cannot autophosphorylate in vitro and which cannot support chemotaxis in vivo. We
      also show that in vitro, the nonphosphorylatable CheA(S) protein mediates
      transphosphorylation of a CheA(L) variant defective in both G1 and G2. In
      contrast, CheA(L) variants defective for either G1 or G2 mediate
      transphosphorylation of each other poorly, if at all. These results are
      consistent with a mechanism by which the G1 and G2 regions of one protomer of a
      CheA dimer form a unit that mediates transphosphorylation of the other protomer
      within that dimer.

PMID- 9006040
TI  - Adaptation to sulfonamide resistance in Neisseria meningitidis may have required
      compensatory changes to retain enzyme function: kinetic analysis of
      dihydropteroate synthases from N. meningitidis expressed in a knockout mutant of
      Escherichia coli.
AB  - Previously, the effects of three point mutations (at amino acid positions 31, 84,
      and 194) in the gene coding for a sulfonamide-resistant dihydropteroate synthase
      of Neisseria meningitidis were analyzed by site-directed mutagenesis. Changes at
      positions 31 and 194 abolished the phenotypic expression of sulfonamide
      resistance, while a change at position 84 appeared to be neutral. These studies
      are here extended to correlate the alterations in phenotype with effects on
      enzyme kinetics by expressing the cloned meningococcal genes in an Escherichia
      coli strain that had its dhps gene partially deleted and replaced by a resistance
      determinant. The most dramatic effects were produced by mutations at position 31.
      A change from the Leu found in the resistant isolate to a Phe (the residue found
      in sensitive isolates) led to a 10-fold decrease in the Km and a concomitant drop
      in the Ki. Changes at position 194 also affected both the Km and Ki but not to
      the same extent as mutations at position 31. Changing position 84 altered the Km
      only slightly but significantly. This latter change was interpreted as a
      compensatory change modulating the function of the enzyme. In another type of
      resistance gene, 2 amino acid residues, proposed to be an insertion, were
      deleted, resulting in a sensitive enzyme. However, the resulting Km was raised 10
      fold, suggesting that compensatory changes have accumulated in this type of
      resistance determinant as well. This resistance gene differs by as much as 10%
      from the sensitive isolates, which makes identification of important mutations
      difficult.

PMID- 9006042
TI  - Reconstitution of trimethylamine-dependent coenzyme M methylation with the
      trimethylamine corrinoid protein and the isozymes of methyltransferase II from
      Methanosarcina barkeri.
AB  - Reconstitution of trimethylamine-dependent coenzyme M (CoM) methylation was
      achieved with three purified polypeptides. Two of these polypeptides copurified
      as a trimethylamine methyl transfer (TMA-MT) activity detected by stimulation of
      the TMA:CoM methyl transfer reaction in cell extracts. The purified TMA-MT
      fraction stimulated the rate of methyl-CoM formation sevenfold, up to 1.7
      micromol/min/mg of TMA-MT protein. The TMA-MT polypeptides had molecular masses
      of 52 and 26 kDa. Gel permeation of the TMA-MT fraction demonstrated that the 52
      kDa polypeptide eluted with an apparent molecular mass of 280 kDa. The 26-kDa
      protein eluted primarily as a monomer, but some 26-kDa polypeptides also eluted
      with the 280-kDa peak, indicating that the two proteins weakly associate. The two
      polypeptides could be completely separated using gel permeation in the presence
      of sodium dodecyl sulfate. The corrinoid remained associated with the 26-kDa
      polypeptide at a molar ratio of 1.1 corrin/26-kDa polypeptide. This polypeptide
      was therefore designated the TMA corrinoid protein, or TCP. The TMA-MT
      polypeptides, when supplemented with purified methylcorrinoid:CoM
      methyltransferase (MT2), could effect the demethylation of TMA with the
      subsequent methylation of CoM and the production of dimethylamine at specific
      activities of up to 600 nmol/min/mg of TMA-MT protein. Neither dimethylamine nor
      monomethylamine served as the substrate, and the activity required Ti(III)
      citrate and methyl viologen. TMA-MT could interact with either isozyme of MT2 but
      had the greatest affinity for the A isozyme. These results suggest that TCP is
      uniquely involved in TMA-dependent methanogenesis, that this corrinoid protein is
      methylated by the substrate and demethylated by either isozyme of MT2, and that
      the predominant isozyme of MT2 found in TMA-grown cells is the favored
      participant in the TMA:CoM methyl transfer reaction.

PMID- 9006041
TI  - Utilization of host iron sources by Corynebacterium diphtheriae: identification
      of a gene whose product is homologous to eukaryotic heme oxygenases and is
      required for acquisition of iron from heme and hemoglobin.
AB  - Corynebacterium diphtheriae was examined for the ability to utilize various host
      compounds as iron sources. C. diphtheriae C7(-) acquired iron from heme,
      hemoglobin, and transferrin. A siderophore uptake mutant of strain C7 was unable
      to utilize transferrin but was unaffected in acquisition of iron from heme and
      hemoglobin, which suggests that C. diphtheriae possesses a novel mechanism for
      utilizing heme and hemoglobin as iron sources. Mutants of C. diphtheriae and
      Corynebacterium ulcerans that are defective in acquiring iron from heme and
      hemoglobin were isolated following chemical mutagenesis and streptonigrin
      enrichment. A recombinant clone, pCD293, obtained from a C7(-) genomic plasmid
      library complemented several of the C. ulcerans mutants and three of the C.
      diphtheriae mutants. The nucleotide sequence of the gene (hmuO) required for
      complementation was determined and shown to encode a protein with a predicted
      mass of 24,123 Da. Sequence analysis revealed that HmuO has 33% identity and 70%
      similarity with the human heme oxygenase enzyme HO-1. Heme oxygenases, which have
      been well characterized in eukaryotes but have not been identified in
      prokaryotes, are involved in the oxidation of heme and subsequent release of iron
      from the heme moiety. It is proposed that the HmuO protein is essential for the
      utilization of heme as an iron source by C. diphtheriae and that the heme
      oxygenase activity of HmuO is involved in the release of iron from heme. This is
      the first report of a bacterial gene whose product has homology to heme
      oxygenases.

PMID- 9006043
TI  - Amino acid transport in taxonomically diverse cyanobacteria and identification of
      two genes encoding elements of a neutral amino acid permease putatively involved
      in recapture of leaked hydrophobic amino acids.
AB  - The activities of uptake of thirteen 14C-labeled amino acids were determined in
      nine cyanobacteria, including the unicellular strains Synechococcus sp. strain
      PCC 7942 and Synechocystis sp. strain PCC 6803; the filamentous strain
      Pseudanabaena sp. strain PCC 6903, and the filamentous, heterocyst-forming
      strains Anabaena sp. strains PCC 7120 and PCC 7937; Nostoc sp. strains PCC 7413
      and PCC 7107; Calothrix sp. strain PCC 7601 (which is a mutant unable to develop
      heterocysts); and Fischerella muscicola UTEX 1829. Amino acid transport mutants,
      selected as mutants resistant to some amino acid analogs, were isolated from the
      Anabaena, Nostoc, Calothrix, and Pseudanabaena strains. All of the tested
      cyanobacteria bear at least a neutral amino acid transport system, and some
      strains also bear transport systems specific for basic or acidic amino acids. Two
      genes, natA and natB, encoding elements (conserved component, NatA, and
      periplasmic binding protein, NatB) of an ABC-type permease for neutral amino
      acids were identified by insertional mutagenesis of strain PCC 6803 open reading
      frames from the recently published genomic DNA sequence of this cyanobacterium.
      DNA sequences homologous to natA and natB from strain PCC 6803 were detected by
      hybridization in eight cyanobacterial strains tested. Mutants unable to transport
      neutral amino acids, including natA and natB insertional mutants, accumulated in
      the extracellular medium a set of amino acids that always included Ala, Val, Phe,
      Ile, and Leu. A general role for a cyanobacterial neutral amino acid permease in
      recapture of hydrophobic amino acids leaked from the cells is suggested.

PMID- 9006044
TI  - Construction and characterization of a mutant of alkaliphilic Bacillus firmus OF4
      with a disrupted cta operon and purification of a novel cytochrome bd.
AB  - The caa3-type terminal oxidase of Bacillus firmus OF4 has been proposed to play
      an important role in the growth and bioenergetics of this alkaliphile (A. A.
      Guffanti and T. A. Krulwich, J. Biol. Chem. 267:9580-9588, 1992). A mutant strain
      was generated in which the cta operon encoding the oxidase was disrupted by
      insertion of a spectinomycin resistance cassette. The mutant was unable to
      oxidize ascorbate in the presence of N,N,N',N'-tetramethyl-p-phenylenediamine
      (TMPD). Absorption spectra of membranes confirmed the loss of the enzyme and
      indicated the presence of a cytochrome bd-type terminal oxidase. The mutant could
      grow on glucose but was unable to grow on malate or other nonfermentative carbon
      sources, despite the presence of the cytochrome bd. The cytochrome bd was
      purified from the mutant. The enzyme consisted of two subunits and, with menadiol
      as substrate, consumed oxygen with a specific activity of 12 micromol of O2 x
      min(-1) x mg(-1). In contrast to both cytochromes bd of Escherichia coli, the
      enzyme did not utilize TMPD as an electron source. A number of additional
      features, including subunit size and spectral properties, distinguish this
      cytochrome bd from its counterparts in E. coli and Azotobacter vinelandii.

PMID- 9006045
TI  - Structure-function studies of the adenylate cyclase toxin of Bordetella pertussis
      and the leukotoxin of Pasteurella haemolytica by heterologous C protein
      activation and construction of hybrid proteins.
AB  - The adenylate cyclase toxin (CyaA) from Bordetella pertussis and the leukotoxin
      (LktA) from Pasteurella haemolytica are members of the RTX (stands for repeats in
      toxin) family of cytolytic toxins. They have pore-forming activity and share
      significant amino acid homology but show marked differences in biological
      activity. CyaA is an invasive adenylate cyclase and a weak hemolysin which is
      active on a wide range of mammalian cells. LktA is a cytolytic protein with a
      high target cell specificity and is able to lyse only leukocytes and platelets
      from ruminants. Each toxin is synthesized as an inactive protoxin encoded by the
      A gene, and the product of the accessory C gene is required for posttranslational
      activation. Heterologous activation of LktA by CyaC did not result in a change in
      its specificity for nucleated cells, although the toxin showed a greater
      hemolytic-to-cytotoxic ratio. LktC was unable to activate CyaA. A hybrid toxin
      (Hyb1), which contained the N-terminal enzymic domain and the pore-forming domain
      from CyaA (amino acids [aa] 1 to 687), with the remainder of the protein derived
      from the C-terminal end of LktA (aa 379 to 953), showed no toxic activity.
      Replacement of part of the LktA C-terminal domain of Hyb1 by the CyaA C-terminal
      domain (aa 919 to 1706) to create hybrid toxin 2 (Hyb2) partially restored toxic
      activity. In contrast to CyaA, Hyb2 was activated more efficiently by LktC than
      by CyaC, showing the importance of the region between aa 379 and 616 of LktA for
      activation by LktC. LktC-activated Hyb2 was more active against ruminant than
      murine nucleated cells, whereas CyaC-activated Hyb2 displayed a similar, but
      lower, activity against both cell types. These data indicate that LktC and the
      region with which it interacts have an influence on the target cell specificity
      of the mature toxin.

PMID- 9006046
TI  - Stability of linear DNA in recA mutant Escherichia coli cells reflects ongoing
      chromosomal DNA degradation.
AB  - To study the fate of linear DNA in Escherichia coli cells, we linearized plasmid
      DNA at a specific site in vivo and monitored its behavior in recA mutant cells
      deficient in recombinational repair. Earlier, we had found that in wild-type (WT)
      cells linearized DNA is degraded to completion by RecBCD nuclease. We had also
      found that in WT cells chi sites on linear DNA inhibit RecBCD degradation by
      turning off its nucleolytic activities. Now we report that chi sites do not work
      in the absence of the RecA protein, suggesting that RecA is required in vivo to
      turn off the degradative activities of the RecBCD enzyme. We also report that the
      degradation of linearized plasmid DNA, even devoid of chi sites, is never
      complete in recA cells. Investigation of this linear DNA stability indicates that
      a fraction of recA cells are recBC phenocopies due to ongoing chromosomal DNA
      degradation, which titrates RecBCD nuclease. A possible role for RecBCD-promoted
      DNA degradation in controlling chromosomal DNA replication in E. coli is
      discussed.

PMID- 9006047
TI  - Hydrogen regulation of growth, growth yields, and methane gene transcription in
      Methanobacterium thermoautotrophicum deltaH.
AB  - Changes in growth rate, methanogenesis, growth yield (Y(CH4)), and methane gene
      transcription have been correlated with changes in the supply of H2 to
      Methanobacterium thermoautotrophicum deltaH cells growing on H2 plus CO2 in fed
      batch cultures. Under conditions of excess H2, biomass and methanogenesis
      increased exponentially and in parallel, resulting in cultures with a constant
      Y(CH4) and transcription of the mth and mrt genes that encode the H2-dependent
      N5,N10-methenyltetrahydromethanopterin (methenyl-H4MPT) reductase (MTH) and
      methyl coenzyme M reductase II (MRII), respectively. Reducing the H2 supply, by
      decreasing the percentage of H2 in the input gas mixture or by reducing the
      mixing speed of the fermentor impeller, decreased the growth rate and resulted in
      lower and constant rates of methanogenesis. Under such H2-limited growth
      conditions, cultures grew with a continuously increasing Y(CH4) and the mtd and
      mcr genes that encode the reduced coenzyme F420-dependent N5,N10-methenyl-H4MPT
      reductase (MTD) and methyl coenzyme M reductase I (MRI), respectively, were
      transcribed. Changes in the kinetics of growth, methanogenesis, and methane gene
      transcription directed by reducing the H2 supply could be reversed by restoring a
      high H2 supply. Methane production continued, but at a low and constant rate, and
      only mcr transcripts could be detected when the H2 supply was reduced to a level
      insufficient for growth. ftsA transcripts, which encode coenzyme F390 synthetase,
      were most abundant in cells growing with high H2 availability, consistent with
      coenzyme F390 synthesis signaling a high exogenous supply of reductant.

PMID- 9006049
TI  - The Escherichia coli stpA gene is transiently expressed during growth in rich
      medium and is induced in minimal medium and by stress conditions.
AB  - The transcriptional regulation of the stpA gene, encoding the Escherichia coli H
      NS-like protein StpA, has been studied as a function of a variety of
      environmental conditions, and its response to trans-acting factors has been
      characterized. Chromosomally located stpA is expressed primarily from a promoter
      immediately upstream of the gene which is severely repressed by the homologous
      nucleoid-associated protein H-NS. However, we show here that even in a strain
      containing functional H-NS, stpA is transiently induced during growth of a batch
      culture in rich medium. It can also be induced strongly by osmotic shock and, to
      a lesser extent, by an increase in growth temperature. Moreover, when cells are
      grown in minimal medium, we observe a more sustained induction of stpA which is
      dependent on the leucine-responsive regulatory protein (Lrp). This enhanced level
      of stpA transcription is virtually abolished in an H-NS-independent manner when
      the culture undergoes carbon starvation. A sensitivity of the stpA promoter to
      DNA topology may contribute to some of these responses. Results reported here
      show that cloned fragments of the stpA promoter region can confer H-NS and Lrp
      responsiveness upon a lacZ reporter gene and suggest that several hundred base
      pairs of DNA upstream of the transcriptional start may be required for regulation
      by these two proteins.

PMID- 9006048
TI  - Growth- and substrate-dependent transcription of the formate dehydrogenase
      (fdhCAB) operon in Methanobacterium thermoformicicum Z-245.
AB  - The formate dehydrogenase-encoding fdhCAB operon and flanking genes have been
      cloned and sequenced from Methanobacterium thermoformicicum Z-245. fdh
      transcription was shown to be initiated 21 bp upstream from fdhC, although most
      fdh transcripts terminated or were processed between fdhC and fdhA. The resulting
      fdhC, fdhAB, and fdhCAB transcripts were present at all growth stages in cells
      growing on formate but were barely detectable during early exponential growth on
      H2 plus CO2. The levels of the fdh transcripts did, however, increase
      dramatically in cells growing on H2 plus CO2, coincident with the decrease in the
      growth rate and the onset of constant methanogenesis that occurred when culture
      densities reached an optical density at 600 nm of approximately 0.5. The mth
      transcript that encodes the H2-dependent methenyl-H4 MPT reductase (MTH) and the
      frh and mvh transcripts that encode the coenzyme F420-reducing (FRH) and
      nonreducing (MVH) hydrogenases, respectively, were also present in cells growing
      on formate, consistent with the synthesis of three hydrogenases, MTH, FRH, and
      MVH, in the absence of exogenously supplied H2. Reducing the H2 supply to M.
      thermoformicicum cells growing on H2 plus CO2 reduced the growth rate and CH4
      production but increased frh and fdh transcription and also increased
      transcription of the mtd, mer, and mcr genes that encode enzymes that catalyze
      steps 4, 5, and 7, respectively, in the pathway of CO2 reduction to CH4. Reducing
      the H2 supply to a level insufficient for growth resulted in the disappearance of
      all methane gene transcripts except the mcr transcript, which increased. Regions
      flanking the fdhCAB operon in M. thermoformicicum Z-245 were used as probes to
      clone the homologous region from the Methanobacterium thermoautotrophicum deltaH
      genome. Sequencing revealed the presence of very similar genes except that the
      genome of M. thermoautotrophicum, a methanogen incapable of growth on formate,
      lacked the fdhCAB operon.

PMID- 9006051
TI  - Propionate catabolism in Salmonella typhimurium LT2: two divergently transcribed
      units comprise the prp locus at 8.5 centisomes, prpR encodes a member of the
      sigma-54 family of activators, and the prpBCDE genes constitute an operon.
AB  - We present the initial genetic and biochemical characterization of the propionate
      (prp) locus at 8.5 centisomes of the Salmonella typhimurium LT2 chromosome (T. A.
      Hammelman et al., FEMS Microbiol. Lett. 137: 233-239, 1996). In this paper, we
      report the nucleotide sequences of two divergently transcribed transcriptional
      units. One unit is comprised of the prpR gene (1,626 bp) encoding a member of the
      sigma-54 family of transcriptional activators; the second unit contains an operon
      of four genes designated prpB (888 bp), prpC (1,170 bp), prpD (1,452 bp), and
      prpE (1,923 bp). The heme biosynthetic gene hemB was shown by DNA sequencing to
      be located immediately downstream of the prpBCDE operon; hemB is divergently
      transcribed from prpBCDE and is separated from prpE by a 66-bp gap. In addition,
      we demonstrate the involvement of PrpB, PrpC, and PrpD in propionate catabolism
      by complementation analysis of mutants using plasmids carrying a single prp gene
      under the control of the arabinose-responsive P(BAD) promoter. Expression of prpB
      to high levels was deleterious to the growth of a prp+ strain on minimal medium
      supplemented with propionate as a carbon and energy source. We also report the
      cloning and overexpression of prpB, prpC, prpD, and prpE in the T7 system. PrpB,
      PrpC, PrpD, and PrpE had molecular masses of ca. 32, ca. 44, ca. 53, and ca. 70
      kDa, respectively. PrpB showed homology to carboxyphosphonoenolpyruvate
      phosphonomutase of Streptomyces hygroscopicus and to its homolog in the carnation
      Dianthus caryophyllus; PrpC was homologous to both archaeal and bacterial citrate
      synthases; PrpD showed homology to yeast and Bacillus subtilis proteins of
      unknown function; PrpE showed homology to acetyl coenzyme A synthetases. We
      identified a sigma-54 (RpoN)-dependent promoter with a consensus RpoN binding
      site upstream of the initiating methionine codon of prpB, the promoter-proximal
      gene of the prp operon. Consistent with this finding, an rpoN prp+ mutant failed
      to use propionate as carbon and energy source. Finally, we report the location of
      MudI1734 elements inserted in prpC or prpD and of a Tn10delta16delta17 element in
      prpB and provide genetic evidence supporting the conclusion that the prpBCDE
      genes constitute an operon.

PMID- 9006050
TI  - Characterization of the p-toluenesulfonate operon tsaMBCD and tsaR in Comamonas
      testosteroni T-2.
AB  - Comamonas testosteroni T-2 uses a standard, if seldom examined, attack on an
      aromatic compound and oxygenates the side chain of p-toluenesulfonate (TS) (or p
      toluenecarboxylate) to p-sulfobenzoate (or terephthalate) prior to complete
      oxidation. The expression of the first three catabolic enzymes in the pathway,
      the TS methyl-monooxygenase system (comprising reductase B and oxygenase M;
      TsaMB), p-sulfobenzyl alcohol dehydrogenase (TsaC), and p-sulfobenzaldehyde
      dehydrogenase (TsaD), is coregulated as regulatory unit R1 (H. R. Schlafli
      Oppenberg, G. Chen, T. Leisinger, and A. M. Cook, Microbiology [Reading] 141:1891
      1899, 1995). The components of the oxygenase system were repurified, and the N
      terminal amino acid sequences were confirmed and extended. An internal sequence
      of TsaM was obtained, and the identity of the [2Fe-2S] Rieske center was
      confirmed by electron paramagnetic resonance spectroscopy. We purified both
      dehydrogenases (TsaC and TsaD) and determined their molecular weights and N
      terminal amino acid sequences. Oligonucleotides derived from the partial
      sequences of TsaM were used to identify cloned DNA from strain T-2, and about 6
      kb of contiguous cloned DNA was sequenced. Regulatory unit R1 was presumed to
      represent a four-gene operon (tsaMBCD) which was regulated by the LysR-type
      regulator, TsaR, encoded by a deduced one-gene transcriptional unit. The genes
      for the inducible TS transport system were not at this locus. The oxygenase
      system was confirmed to be a class IA mononuclear iron oxygenase, and class IA
      can now be seen to have two evolutionary groups, the monooxygenases and the
      dioxygenases, though the divergence is limited to the oxygenase components. The
      alcohol dehydrogenase TsaC was confirmed to belong to the short-chain, zinc
      independent dehydrogenases, and the aldehyde dehydrogenase TsaD was found to
      resemble several other aldehyde dehydrogenases. The operon and its putative
      regulator are compared with units of the TOL plasmid.

PMID- 9006053
TI  - Dihydroneopterin triphosphate epimerase of Escherichia coli: purification,
      genetic cloning, and expression.
AB  - The enzyme catalyzing the epimerization at position 2' of dihydroneopterin
      triphosphate was purified by a factor of about 10,000 from cell extract of
      Escherichia coli. The cognate gene was cloned, sequenced, expressed, and mapped
      to kb 2427 on the E. coli chromosome.

PMID- 9006052
TI  - Properties and gene structure of the Thermotoga maritima alpha-amylase AmyA, a
      putative lipoprotein of a hyperthermophilic bacterium.
AB  - Thermotoga maritima MSB8 has a chromosomal alpha-amylase gene, designated amyA,
      that is predicted to code for a 553-amino-acid preprotein with significant amino
      acid sequence similarity to the 4-alpha-glucanotransferase of the same strain and
      to alpha-amylase primary structures of other organisms. Upstream of the amylase
      gene, a divergently oriented open reading frame which can be translated into a
      polypeptide with similarity to the maltose-binding protein MalE of Escherichia
      coli was found. The T. maritima alpha-amylase appears to be the first known
      example of a lipoprotein alpha-amylase. This is in agreement with observations
      pointing to the membrane localization of this enzyme in T. maritima. Following
      the signal peptide, a 25-residue putative linker sequence rich in serine and
      threonine was found. The amylase gene was expressed in E. coli, and the
      recombinant enzyme was purified and characterized. The molecular mass of the
      recombinant enzyme was estimated at 61 kDa by denaturing gel electrophoresis (63
      kDa by gel permeation chromatography). In a 10-min assay at the optimum pH of
      7.0, the optimum temperature of amylase activity was 85 to 90 degrees C. Like the
      alpha-amylases of many other organisms, the activity of the T. maritima alpha
      amylase was dependent on Ca2+. The final products of hydrolysis of soluble starch
      and amylose were mainly glucose and maltose. The extraordinarily high specific
      activity of the T. maritima alpha-amylase (about 5.6 x 10(3) U/mg of protein at
      80 degrees C, pH 7, with amylose as the substrate) together with its extreme
      thermal stability makes this enzyme an interesting candidate for biotechnological
      applications in the starch processing industry.

PMID- 9006055
TI  - Isolation and characterization of a priB mutant of Escherichia coli influencing
      plasmid copy number of delta rop ColE1-type plasmids.
AB  - The lethality induced by the overproduction in Escherichia coli of a heterologous
      protein was used to select bacterial mutants. In one of these, the mutation
      responsible was mapped to priB. We describe the isolation of this mutant, the
      sequencing of the mutated gene, and its in vivo effect on plasmid replication.

PMID- 9006054
TI  - Effect of lipopolysaccharide mutations on recipient ability of Salmonella
      typhimurium for incompatibility group H plasmids.
AB  - Previous investigations of the incompatibility group F, P, and I plasmid systems
      revealed the important role of the outer membrane components in the conjugal
      transfer of these plasmids. We have observed variability in transfer frequency of
      three incompatibility group H plasmids (IncHI1 plasmid R27, IncHI2 plasmid R478,
      and a Tn7 derivative of R27, pDT2454) upon transfer into various Salmonella
      typhimurium lipopolysaccharide (LPS) mutants derived from a common parental
      strain, SL1027. Recipients with truncated outer core via the rfaF LPS mutation
      increased the transfer frequency of the IncH plasmids by up to a factor of 10(3).
      Mutations which resulted in the truncation of the residues following 3-deoxy-D
      manno-octulosonic acid, such as the rfaE and rfaD mutations, decreased the
      transfer frequency to undetectable levels. Addition of phosphorylethanolamine, a
      component of wild-type LPS, to the media decreased the frequency of transfer of
      R27 into wild-type and rfaF LPS mutant recipients tested. Reversing the direction
      of transfer, by mating LPS mutant donors with wild-type recipients, did not
      affect the frequency of transfer compared to the standard matings of wild-type
      donor with LPS mutant recipient. These findings demonstrate that conjugation
      interactions affected by LPS mutation are not specific for the recipient cell.
      Our results suggest that LPS mutation does not affect conjugation via altered
      pilus binding but affects some later steps in the conjugative process, and
      alteration of transfer frequency by O-phosphorylethanolamine and LPS truncation
      is due to charge-related interactions between the donor and recipient cell.

PMID- 9006056
TI  - Variation in RNA polymerase sigma subunit composition within different stocks of
      Escherichia coli W3110.
AB  - The composition of RNA polymerase sigma subunits was analyzed for stock strains
      of Escherichia coli K-12 W3110 in Japan. Heterogeneity was discovered with
      respect to two sigma subunits, sigma28 (sigmaF, the rpoF gene product) and
      sigma38 (sigmaS, the rpoS gene product). Five different types of W3110 were
      identified: A-type lineages have both sigma subunits in intact forms; B-type
      lineages carry a truncated sigma38 subunit and an intact sigma28 subunit; C-type
      lineages carry an intact sigma28 subunit but lack a sigma38 subunit; D-type
      lineages have only a sigma38 subunit without a sigma28 subunit; and E-type stocks
      lack both sigma subunits. All the lineages examined, however, contain the intact
      forms of sigma70 (sigmaD, the rpoD gene product) and sigma54 (sigmaN, the rpoN
      gene product). As expected from the lack of a sigma28 subunit, cells of D- and E
      type lineages are nonmotile. The truncated form of the sigma38 subunit in B-type
      stocks carries two mutations near its N terminus and lacks C-terminal proximal
      region 4 due to an amber mutation. The failure of C- and E-type W3110 cells to
      express sigma38 and that of D- and E-type cells to express sigma28 were found to
      be due to defects in transcription even though the respective sigma subunit genes
      remain intact. These findings emphasize the importance of paying attention to
      possible variations in the genetic background between laboratory stocks
      originating from the same strain.

PMID- 9006057
TI  - Characterization of the intergenic region which regulates the MspI restriction
      modification system.
AB  - The 110-bp intergenic region between mspIM and mspIR, the genes encoding the MspI
      modification (M.MspI) and restriction (R.MspI) enzymes, respectively, was fused,
      in both orientations, with lacZ. Expression of a single-copy mspIM-lacZ fusion is
      more than 400-fold stronger than expression of an mspIR-lacZ fusion. M.MspI in
      trans represses expression of the mspIM-lacZ fusion by binding to the DNA but
      does not affect expression of the mspIR-lacZ fusion. Transcription start sites of
      the genes were identified, and a set of nonoverlapping promoters was assigned.
      DNase I footprinting showed that M.MspI binds to a site within the intergenic
      region that includes only the mspIM regulatory elements.

PMID- 9006058
TI  - Purification and in vitro phosphorylation of HupT, a regulatory protein
      controlling hydrogenase gene expression in Rhodobacter capsulatus.
AB  - The HupT protein of Rhodobacter capsulatus, involved in negative regulation of
      hydrogenase gene expression, is predicted to be a histidine kinase on the basis
      of sequence comparisons. The protein was overproduced in Escherichia coli,
      purified to homogeneity, and demonstrated to autophosphorylate in vitro in the
      presence of [gamma-32P]ATP. An H217N hupt mutant was constructed, and the mutant
      protein was shown to have lost kinase activity. This result, and the fact that
      the phosphoryl group in phosphorylated HupT appeared to be bound to an N atom,
      support the suggestion from sequence comparisons that HupT is a histidine kinase,
      which can autophosphorylate on the His217 residue.

PMID- 9006059
TI  - Bacillus subtilis SpoIIID protein binds to two sites in the spoVD promoter and
      represses transcription by sigmaE RNA polymerase.
AB  - The Bacillus subtilis spoVD gene encodes a penicillin-binding protein required
      for spore morphogenesis. SpoIIID is a sequence-specific DNA-binding protein that
      activates or represses the transcription of many different genes. We have defined
      the spoVD promoter region and demonstrated that it is recognized by sigmaE RNA
      polymerase in vitro and that SpoIIID represses spoVD transcription. Two strong
      SpoIIID-binding sites were mapped in the spoVD promoter region, one overlapping
      the -35 region and the other encompassing the -10 region and the transcriptional
      start site.

PMID- 9006061
TI  - Antigenic variation in Neisseria gonorrhoeae: production of multiple
      lipooligosaccharides.
AB  - Individual cells of Neisseria gonorrhoeae may express a single
      lipooligosaccharide (LOS) component on their cell surfaces, or they may
      simultaneously express multiple LOS structures. Strain FA19 expresses LOS
      components that react with monoclonal antibodies (MAbs) 2-1-L8 and 1B2. The
      genetic locus responsible for this phenotype in FA19 was identified by isolating
      a clone that is able to impart the ability to simultaneously express both LOS
      molecules to strain 1291, a strain expressing only the MAb 1B2-reactive LOS. This
      clone, pCLB1, was characterized, and the gene responsible for the expression of
      both LOS components was determined to be lsi2. DNA sequence analysis of
      lsi2(Fa19) indicates that there are several differences between the DNA sequences
      of lsi2(FA19) and lsi2(1291). The region responsible for the LOS-specific
      phenotype change in lsi2(FA19) was identified by deletion and transformation
      analysis, mapping to a polyguanine tract within lsi2 where lsi2(FA19) possesses a
      +2 frameshift relative to lsi2(1291). The polyguanine tract in lsi2(FA19) was
      modified by site-directed mutagenesis to change the sequence to GGGAGGTGGCGGA to
      prevent frameshifting during DNA replication, transcription, and/or translation.
      Transformants of strain 1291 containing this DNA sequence express a single MAb 2
      1-L8-reactive LOS component, the same phenotype exhibited by lsi2-defective
      strains. These data indicate that FA19 is able to generate a small amount of
      functional Lsi2 protein via transcriptional and/or translational frameshifting,
      and this limited amount of protein allows for the expression of MAb 1B2-reactive
      LOS molecules.

PMID- 9006062
TI  - BMP-7 influences pattern and growth of the developing hindbrain of mouse embryos.
AB  - The expression pattern of bone morphogenetic protein-7 (BMP-7) in the hindbrain
      region of the headfold and early somite stage developing mouse embryo suggests a
      role for BMP-7 in the patterning of this part of the cranial CNS. In chick
      embryos it is thought that BMP-7 is one of the secreted molecules which mediates
      the dorsalizing influence of surface ectoderm on the neural tube, and mouse
      surface ectoderm has been shown to have a similar dorsalizing effect. While we
      confirm that BMP-7 is expressed in the surface ectoderm of mouse embryos at the
      appropriate time to dorsalize the neural tube, we also show that at early stages
      of hindbrain development BMP-7 transcripts are present in paraxial and ventral
      tissues, within and surrounding the hindbrain neurectoderm, and only later does
      expression become restricted to a dorsal domain. To determine more directly the
      effect that BMP-7 may have on the developing hindbrain we have grafted COS cells
      expressing BMP-7 into the ventrolateral mesoderm abutting the neurectoderm in
      order to prolong BMP-7 expression in the vicinity of ventral hindbrain. Three
      distinct actvities of BMP-7 are apparent. Firstly, as expected from previous work
      in chick, BMP-7 can promote dorsal characteristics in the neural tube. Secondly,
      we show that it can also attenuate the expression of sonic hedgehog (Shh) in the
      floorplate without affecting Shh expression in the notochord. Finally, we find
      that ectopic BMP-7 appears to promote growth of the neurectoderm. These findings
      are discussed with respect to possible timing mechanisms necessary for the
      coordination of hindbrain dorsoventral patterning.

PMID- 9006060
TI  - L-cysteine biosynthesis in Bacillus subtilis: identification, sequencing, and
      functional characterization of the gene coding for phosphoadenylylsulfate
      sulfotransferase.
AB  - Random Tn917 mutagenesis of Bacillus subtilis followed by selection of lipoic
      acid auxotrophs led to the isolation of the cysH gene. The gene was sequenced and
      found to encode a phosphoadenylylsulfate sulfotransferase with a molecular mass
      of 27 kDa. Expression of lacZ fused to the cysH promoter was repressed by
      cysteine and sulfide and induced by sulfur limitation, indicating that cysH is
      controlled at the level of transcription.

PMID- 9006063
TI  - Multiple signaling events specify ectoderm and pattern the oral-aboral axis in
      the sea urchin embryo.
AB  - In the sea urchin embryo, the animal-vegetal axis is established during oogenesis
      and the oral-aboral axis is specified sometime after fertilization. The
      mechanisms by which either of these axes are specified and patterned during
      embryogenesis are poorly understood. Here, we investigated the role of cellular
      interactions in the specification of the ectoderm territories and polarization of
      the ectoderm along the oral-aboral axis. Isolated animal halves (mesomeres),
      which are fated to give rise to oral and aboral ectoderm, developed into
      polarized embryoids that expressed an oral ectoderm-specific marker uniformly.
      These embryoids also produced neuron-like cells and serotonergic neurons,
      suggesting that mesomeres are autonomously specified as oral ectoderm. Mesomere
      derived embryoids did not express any aboral ectoderm-specific markers, although
      we previously showed that aboral ectoderm-specific genes can be induced by 25 mM
      lithium chloride, which also induced endoderm formation (Wikramanayake, A. H.,
      Brandhorst, B. P. and Klein, W. H.(1995). Development 121, 1497-1505). To
      ascertain if endoderm formation is a prerequisite for induction of aboral
      ectoderm by lithium and for normal ectoderm patterning in animal halves, we
      modulated the lithium treatment to ensure that no endoderm formed. Remarkably,
      treating animal halves with 10 mM LiCl at approximately 7 hours postfertilization
      resulted in embryoids that displayed oral-aboral axis patterning in the absence
      of endoderm. Application of 25 mM LiCl to animal halves at approximately 16 hours
      postfertilization, which also did not induce endoderm, resulted in polarized
      expression of the aboral ectoderm-specific LpS1 protein, but global expression of
      the Ecto V antigen and no induction of the stomodeum or ciliary band. These
      results suggest that at least two signals, a positive inductive signal to specify
      the aboral ectoderm and a negative suppressive signal to inactivate oral ectoderm
      specific genes in the prospective aboral ectoderm territory, are needed for
      correct spatial expression of oral and aboral ectoderm-specific genes.
      Transmission of both these signals may be prerequisite for induction of secondary
      ectodermal structures such as the ciliary band and stomodeum. Thus,
      differentiation of ectoderm and polarization of the oral-aboral axis in
      Lytechinus pictus depends on cellular interactions with vegetal blastomeres as
      well as interactions along the oral-aboral axis.

PMID- 9006065
TI  - Organization and cell differentiation in lateral roots of Arabidopsis thaliana.
AB  - Lateral root formation in plants involves the stimulation of mature pericycle
      cells to proliferate and redifferentiate to create a new organ. The simple
      organization of the root of Arabidopsis thaliana allows the development of
      lateral root primordia to be characterized histologically. We have divided the
      process of lateral root development into 8 stages defined by specific anatomical
      characteristics and cell divisions. To identify the cell types in the developing
      primordium we have generated a collection of marker lines that express beta
      glucuronidase in a tissue- or cell type-specific manner in the root. Using these
      tools we have constructed a model describing the lineage of each cell type in the
      lateral root. These studies show that organization and cell differentiation in
      the lateral root primordia precede the appearance of a lateral root meristem,
      with differential gene expression apparent after the first set of divisions of
      the pericycle.

PMID- 9006064
TI  - The spalt gene links the A/P compartment boundary to a linear adult structure in
      the Drosophila wing.
AB  - During Drosophila embryogenesis, each segment is subdivided into an anterior and
      a posterior compartment through the action of the engrailed gene. Compartmental
      boundaries bisect imaginal disc primordia which give rise to adult appendages. In
      early larval development, a short-range Hedgehog signal originating from the
      posterior compartment of the imaginal wing disc activates expression of genes
      including decapentaplegic (dpp) in a stripe running along the anterior-posterior
      compartment boundary. Secreted Dpp emanating from the A/P boundary of wing discs
      then acts as a secondary signal to organize the wing over large distances. The
      transcription factor encoded by spalt major (salm) gene, which is expressed in a
      broad wedge centered over the dpp stripe, is one target of Dpp signaling. In this
      manuscript, we show that the anterior edge of the salm expression domain abuts a
      narrow stripe of rhomboid (rho)-expressing cells corresponding to the L2
      longitudinal vein primordium. hh mis-expression along the anterior wing margin
      induces a surrounding domain of salm expression, the anterior edge of which abuts
      a displaced rho L2 stripe. salm plays a key role in defining the position of the
      L2 vein since loss of salm function in mosaic patches induces the formation of
      ectopic L2 branches, which comprise salm- cells running along clone borders where
      salm- cells confront salm+ cells. These data suggest that salm determines the
      position of the L2 vein primordium by activating rho expression in neighboring
      cells through a locally non-autonomous mechanism. rho then functions to initiate
      and maintain vein differentiation. We discuss how these data provide the final
      link connecting the formation of a linear adult structure to the establishment of
      a boundary by the maternal Bicoid morphogen gradient in the blastoderm embryo.

PMID- 9006066
TI  - Ectopic eye development in Drosophila induced by directed dachshund expression.
AB  - The dachshund gene encodes a nuclear protein that is required for normal eye
      development in Drosophila. In the absence of dachshund function, flies develop
      with severely reduced or no eyes. We show that targeted expression of dachshund
      is sufficient to direct ectopic retinal development in a variety of tissues,
      including the adult head, thorax and legs. This result is similar to that
      observed with the highly conserved Drosophila gene eyeless, which can induce
      ectopic eye formation on all major appendages. Here, we show that dachshund and
      eyeless induce the expression of each other and that dachshund is required for
      ectopic retinal development driven by eyeless misexpression. These results
      suggest that the control of eye development requires the complex interaction of
      multiple genes, even at the very highest regulatory levels.

PMID- 9006067
TI  - Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and
      morphogenesis.
AB  - Branching morphogenesis of the embryonic lung requires interactions between the
      epithelium and the mesenchyme. Previously, we reported that Sonic hedgehog (Shh)
      transcripts are present in the epithelium of the developing mouse lung, with
      highest levels in the terminal buds. Here, we report that transcripts of mouse
      patched (Ptc), the homologue of a Drosophila gene encoding a putative
      transmembrane protein required for hedgehog signaling, are expressed at high
      levels in the mesenchyme adjacent to the end buds. To investigate the function of
      SHH in lung development, Shh was overexpressed throughout the distal epithelium,
      using the surfactant protein-C (SP-C)-enhancer/promoter. Beginning around 16.5
      dpc, when Shh and Ptc RNA levels are normally both declining, this treatment
      caused an increase in the ratio of interstitial mesenchyme to epithelial tubules
      in transgenic compared to normal lungs. Transgenic newborn mice die soon after
      birth. Histological analysis of the lungs at the light and electron microscope
      level shows an abundance of mesenchyme and the absence of typical alveoli. In
      vivo BrdU labeling indicates that Shh overexpression results in increased
      mesenchymal and epithelial cell proliferation at 16.5 and 17.5 dpc. However,
      analysis of CC-10 and SP-C expression reveals no significant inhibition in the
      differentiation of proximal and distal epithelial cells. The expression of genes
      potentially regulated by SHH was also examined. No difference could be observed
      between transgenic and control lungs in either the level or distribution of Bmp4,
      Wnt2 and Fgf7 RNA. By contrast, Ptc is clearly upregulated in the transgenic
      lung. These results thus establish a role for SHH in lung morphogenesis, and
      suggest that SHH normally regulates lung mesenchymal cell proliferation in vivo.

PMID- 9006068
TI  - Long-range genomic rearrangements upstream of Kit dysregulate the developmental
      pattern of Kit expression in W57 and Wbanded mice and interfere with distinct
      steps in melanocyte development.
AB  - Mutations in the murine dominant white spotting (W) locus cause pleiotropic
      developmental defects that affect hematopoietic cells, melanocytes, germ cells
      and the interstitial cells of Cajal in the gut. W mutations either alter the
      coding sequence of the Kit receptor tyrosine kinase, resulting in a receptor with
      impaired kinase activity, or affect Kit expression. Here we describe the
      molecular and cell-type-specific developmental defects of two of the latter class
      of regulatory W alleles, W57 and Wbanded(bd). In both mutants, the temporal and
      spatial patterns of Kit expression are dysregulated during embryogenesis and in
      adult animals. In Wbd mice, ectopic expression of Kit in the dermatome of the
      somites at days 10.8 and 11.8 of development seemed to interfere with melanoblast
      development. In contrast, the W57 allele leads to an intrinsic pigmentation
      defect by downregulating developmental Kit expression in trunk melanoblasts, but
      not melanoblasts around the otic vesicle. Both mutations affect transcriptional
      initiation of the Kit gene. The W57 allele is associated with a 80 kb deletion 5'
      of the Kit-coding region while Wbd is associated with a 2.8 Mb genomic inversion
      of chromosome 5 with the distal breakpoint between Kit and the platelet-derived
      growth factor receptor alpha (Pdgfra) gene, and the proximal breakpoint between
      the genes for the GABA receptor beta 1 (Gabrb1) and the Tec tyrosine kinase,
      juxtaposing the Kit and Tec tyrosine kinase genes. Neither W57 nor Wbd affect
      genomic sequences previously suggested in in vitro experiments to control cell
      type-specific expression of Kit. These results link specific mechanisms of
      cellular and developmental defects to long-range genomic rearrangements that
      positively and negatively affect Kit transcription in different cell lineages as
      well as in different subpopulations of the same lineage.

PMID- 9006070
TI  - ladybird, a tandem of homeobox genes that maintain late wingless expression in
      terminal and dorsal epidermis of the Drosophila embryo.
AB  - ladybird early and ladybird late genes, tandemly located in the Drosophila 93E
      homeobox gene cluster, encode highly related homeodomain-containing transcription
      factors. Here we report the cloning of the complete cDNA sequences of both genes
      and a study of their expression and regulatory interactions with the segment
      polarity gene wingless in the epidermis. ladybird genes are co-expressed with
      wingless in epidermal cells close to the posterior parasegmental boundaries and
      in terminal regions of the body. In mutant embryos with altered wingless
      function, transcription of ladybird early and ladybird late is changed; it
      disappears completely from the epidermis in wingless-embryos, indicating wingless
      dependence. After 6 hours of development, wingless expression is maintained by
      gooseberry in the ventral epidermis. However, in the dorsal epidermis and the
      terminal regions of the body, expression of wingless is independent of gooseberry
      but requires a wingless-ladybird regulatory feedback loop. Loss of ladybird
      function reduces the number of wingless-expressing cells in dorsal epidermis and
      leads to complete inactivation of wingless in the anal plate. Consequently,
      mutant ladybird embryos fail to develop anal plates and ubiquitous embryonic
      expression of either one or both ladybird genes leads to severe defects of the
      dorsal cuticle. Lack of late wingless expression and anal plate formation can be
      rescued with the use of a heat-shock-ladybird transgene.

PMID- 9006069
TI  - Signaling through both type I DPP receptors is required for anterior-posterior
      patterning of the entire Drosophila wing.
AB  - The imaginal disk expression of the TGF-beta superfamily member DPP in a narrow
      stripe of cells along the anterior-posterior compartment boundary is essential
      for proper growth and patterning of the Drosophila appendages. We examine DPP
      receptor function to understand how this localized DPP expression produces its
      global effects upon appendage development. Clones of saxophone (sax) or thick
      veins (tkv) mutant cells, defective in one of the two type I receptors for DPP,
      show shifts in cell fate along the anterior-posterior axis. In the adult wing,
      clones that are homozygous for a null allele of sax or a hypomorphic allele of
      tkv show shifts to more anterior fates when the clone is in the anterior
      compartment and to more posterior fates when the clone is in the posterior
      compartment. The effect of these clones upon the expression pattern of the
      downstream gene spalt-major also correlates with these specific shifts in cell
      fate. The similar effects of sax null and tkv hypomorphic clones indicate that
      the primary difference in the function of these two receptors during wing
      patterning is that TKV transmits more of the DPP signal than does SAX. Our
      results are consistent with a model in which a gradient of DPP reaches all cells
      in the developing wing blade to direct anterior-posterior pattern.

PMID- 9006071
TI  - Emx1 and Emx2 functions in development of dorsal telencephalon.
AB  - The genes Emx1 and Emx2 are mouse cognates of a Drosophila head gap gene, empty
      spiracles, and their expression patterns have suggested their involvement in
      regional patterning of the forebrain. To define their functions we introduced
      mutations into these loci. The newborn Emx2 mutants displayed defects in
      archipallium structures that are believed to play essential roles in learning,
      memory and behavior: the dentate gyrus was missing, and the hippocampus and
      medial limbic cortex were greatly reduced in size. In contrast, defects were
      subtle in adult Emx1 mutant brain. In the early developing Emx2 mutant forebrain,
      the evagination of cerebral hemispheres was reduced and the roof between the
      hemispheres was expanded, suggesting the lateral shift of its boundary. Defects
      were not apparent, however, in the region where Emx1 expression overlaps that of
      Emx2, nor was any defect found in the early embryonic forebrain caused by
      mutation of the Emx1 gene, of which expression principally occurs within the Emx2
      positive region. Emx2 most likely delineates the palliochoroidal boundary in the
      absence of Emx1 expression during early dorsal forebrain patterning. In the more
      lateral region of telencephalon, Emx2-deficiency may be compensated for by Emx1
      and vice versa. Phenotypes of newborn brains also suggest that these genes
      function in neurogenesis corresponding to their later expressions.

PMID- 9006072
TI  - Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal
      patterning and development.
AB  - The correct patterning of vertebrate skeletal elements is controlled by inductive
      interactions. Two vertebrate hedgehog proteins, Sonic hedgehog and Indian
      hedgehog, have been implicated in skeletal development. During somite
      differentiation and limb development, Sonic hedgehog functions as an inductive
      signal from the notochord, floor plate and zone of polarizing activity. Later in
      skeletogenesis, Indian hedgehog functions as a regulator of chondrogenesis during
      endochondral ossification. The vertebrate Gli zinc finger proteins are putative
      transcription factors that respond to Hedgehog signaling. In Drosophila, the Gli
      homolog cubitus interruptus is required for the activation of hedgehog targets
      and also functions as a repressor of hedgehog expression. We show here that Gli2
      mutant mice exhibit severe skeletal abnormalities including cleft palate, tooth
      defects, absence of vertebral body and intervertebral discs, and shortened limbs
      and sternum. Interestingly, Gli2 and Gli3 (C.-c. Hui and A. L. Joyner (1993).
      Nature Genet. 3, 241-246) mutant mice exhibit different subsets of skeletal
      defects indicating that they implement specific functions in the development of
      the neural crest, somite and lateral plate mesoderm derivatives. Although Gli2
      and Gli3 are not functionally equivalent, double mutant analysis indicates that,
      in addition to their specific roles, they also serve redundant functions during
      skeletal development. The role of Gli2 and Gli3 in Hedgehog signaling during
      skeletal development is discussed.

PMID- 9006073
TI  - Specification of the embryonic limb primordium by graded activity of
      Decapentaplegic.
AB  - Two thoracic limbs of Drosophila, the leg and the wing, originate from a common
      cluster of cells that include the source of two secreted signaling molecules,
      Decapentaplegic and Wingless. We show that Wingless, but not Decapentaplegic, is
      responsible for initial specification of the limb primordia with a distal
      identity. Limb formation is restricted to the lateral position of the embryo by
      negative control of the early function of Decapentaplegic and the EGF receptor
      homolog that determine the global dorsoventral pattern. Late function of
      Decapentaplegic locally determines two additional cell identities in a dosage
      dependent manner. Loss of Decapentaplegic activity results in a deletion of the
      proximal structures of the limb, which is in contrast to the consequence of
      decapentaplegic mutations in the imaginal disc, which cause a deletion of distal
      structures. The results indicate that the limb pattern elements are added in a
      distal to proximal direction in the embryo, which is opposite to what is
      happening in the growing imaginal disc. We propose that Wingless and
      Decapentaplegic act sequentially to initiate the proximodistal axis.

PMID- 9006074
TI  - Limb deformity proteins: role in mesodermal induction of the apical ectodermal
      ridge.
AB  - During early limb development, distal tip ectoderm is induced by the underlying
      mesenchyme to form the apical ectodermal ridge. Subsequent limb growth and
      patterning depend on reciprocal signaling between the mesenchyme and ridge. Mice
      that are homozygous for mutations at the limb deformity (ld) locus do not form a
      proper ridge and the anteroposterior axis of the limb is shortened. Skeletal
      analyses reveal shortened limbs that involve loss and fusion of distal bones and
      digits, defects in both anteroposterior and proximodistal patterning. Using
      molecular markers and mouse-chick chimeras we examined the ridge-mesenchymal
      interactions to determine the origin of the ld patterning defects. In the ld
      ridge, fibroblast growth factor 8 (Fgf8) RNA is decreased and Fgf4 RNA is not
      detected. In the ld mesenchyme, Sonic hedgehog (Shh), Evx1 and Wnt5a expression
      is decreased. In chimeras between ld ectoderm and wild-type mesenchyme, a ridge
      of normal morphology and function is restored, Fgf8 and Shh are expressed
      normally, Fgf4 is induced and a normal skeletal pattern arises. These results
      suggest that the ld mesenchyme is unable to induce the formation of a completely
      functional ridge. This primary defect causes a disruption of ridge function and
      subsequently leads to the patterning defects observed in ld limbs. We propose a
      model in which ridge induction requires at least two phases: an early competence
      phase, which includes induction of Fgf8 expression, and a later differentiation
      phase in which Fgf4 is induced and a morphological ridge is formed. Ld proteins
      appear to act during the differentiation phase.

PMID- 9006075
TI  - Planarian Hox genes: novel patterns of expression during regeneration.
AB  - Platyhelminthes are widely considered to be the sister group of coelomates
      (Philippe, H., Chenuil, A. and Adoutte, A. (1994)Development 1994 Supplement, 15
      24) and the first organisms to show bilateral symmetry and cephalization. Within
      this phylum, the freshwater planarians (Turbellaria, Tricladida) have been used
      as model systems for studying bidirectional regeneration (Slack, J. M. W. (1980)
      J. Theor. Biol 82, 105-140). We have been attempting to identify potential
      pattern-control genes involved in the regeneration of planarian heads and tails
      after amputation. Since Hox cluster genes determine positional identity along the
      anteroposterior axis in a wide range of animals (Slack, J. M. W., Holland, P. W.
      H. and Graham, C. F. (1993) Nature 361,490-492), we performed an extensive search
      for Hox-related genes in the planarian Dugesia(G)tigrina. Sequence analyses of
      seven planarian Dthox genes (Dthox-A to Dthox-G) reveal high similarities with
      the homeodomain region of the Hox cluster genes, allowing us to assign planarian
      Dthox genes to anterior and medial Hox cluster paralogous groups. Whole-mount in
      situ hybridization studies in regenerating adults showed very early, synchronous
      and colocalized activation of Dthox-D, Dthox-A, Dthox-C, Dthox-E, Dthox-G and
      Dthox-F. After one hour of regeneration a clear expression was observed in all
      Dthox genes studied. In addition, all seemed to be expressed in the same
      regenerative tissue, although in the last stages of regeneration (9 to 15 days) a
      differential timing of deactivation was observed. The same Dthox genes were also
      expressed synchronously and were colocalized during intercalary regeneration,
      although their expression was delayed. Terminal regeneration showed identical
      Dthox gene expression in anterior and posterior blastemas, which may prevent
      these genes from directing the distinction between head and tail. Finally,
      continuous expression along the whole lateral blastema in sagittal regenerates
      reflected a ubiquitous Dthox response in all types of regeneration that was not
      related specifically with the anteroposterior polarity.

PMID- 9006077
TI  - Sclerotome development and peripheral nervous system segmentation in embryonic
      zebrafish.
AB  - Vertebrate embryos display segmental patterns in many trunk structures, including
      somites and peripheral nervous system elements. Previous work in avian embryos
      suggests a role for somite-derived sclerotome in segmental patterning of the
      peripheral nervous system. We investigated sclerotome development and tested its
      role in patterning motor axons and dorsal root ganglia in embryonic zebrafish.
      Individual somite cells labeled with vital fluorescent dye revealed that some
      cells of a ventromedial cell cluster within each somite produced mesenchymal
      cells that migrated to positions expected for sclerotome. Individual somites
      showed anterior/posterior distinctions in several aspects of development: (1)
      anterior ventromedial cluster cells produced only sclerotome, (2) individual
      posterior ventromedial cluster cells produced both sclerotome and muscle, and (3)
      anterior sclerotome migrated earlier and along a more restricted path than
      posterior sclerotome. Vital labeling showed that anterior sclerotome colocalized
      with extending identified motor axons and migrating neural crest cells. To
      investigate sclerotome involvement in peripheral nervous system patterning, we
      ablated the ventromedial cell cluster and observed subsequent development of
      peripheral nervous system elements. Primary motor axons were essentially
      unaffected by sclerotome ablation, although in some cases outgrowth was delayed.
      Removal of sclerotome did not disrupt segmental pattern or development of dorsal
      root ganglia or peripheral nerves to axial muscle. We propose that peripheral
      nervous system segmentation is established through interactions with adjacent
      paraxial mesoderm which develops as sclerotome in some vertebrate species and
      myotome in others.

PMID- 9006078
TI  - The role of selectins in Drosophila eye and bristle development.
AB  - Mutations in the furrowed (fw) gene of Drosophila result in defects in the
      development of the eye and mechanosensory bristles. The eyes are reduced in size,
      have furrows or crevices in the retina, and show a disturbed patterning of
      ommatidia. In addition, the ommatidia have an altered morphology and often
      contain abnormal numbers of cells. The bristles show altered structure and
      polarity, and are occasionally duplicated or missing. These results suggest that
      the product of thefw gene is involved in cell determination events within sensory
      organs. Thefw gene has been cloned and shown to encode a protein homologous to
      vertebrate selectins. Like selectins, Fw contains a lectin-binding domain, ten
      complement binding repeats, and a transmembrane domain. The Fw protein is
      expressed in the larval imaginal discs where it might mediate carbohydrate
      protein interactions necessary for proper development of a subset of adult
      sensory organs.

PMID- 9006076
TI  - Evolution of the insect body plan as revealed by the Sex combs reduced expression
      pattern.
AB  - The products of the HOM/Hox homeotic genes form a set of evolutionarily conserved
      transcription factors that control elaborate developmental processes and specify
      cell fates in many metazoans. We examined the expression of the ortholog of the
      homeotic gene Sex combs reduced (Scr) of Drosophila melanogaster in insects of
      three divergent orders: Hemiptera, Orthoptera and Thysanura. Our data reflect how
      the conservation and variation of Scr expression has affected the morphological
      evolution of insects. Whereas the anterior epidermal expression of Scr, in a
      small part of the posterior maxillary and all of the labial segment, is found to
      be in common among all four insect orders, the posterior (thoracic) expression
      domains vary. Unlike what is observed in flies, the Scr orthologs of other
      insects are not expressed broadly over the first thoracic segment, but are
      restricted to small patches. We show here that Scr is required for suppression of
      wings on the prothorax of Drosophila. Moreover, Scr expression at the dorsal base
      of the prothoracic limb in two other winged insects, crickets (Orthoptera) and
      milkweed bugs (Hemiptera), is consistent with Scr acting as a suppressor of
      prothoracic wings in these insects. Scr is also expressed in a small patch of
      cells near the basitarsal-tibial junction of milkweed bugs, precisely where a leg
      comb develops, suggesting that Scr promotes comb formation, as it does in
      Drosophila. Surprisingly, the dorsal prothoracic expression of Scr is also
      present in the primitively wingless firebrat (Thysanura) and the leg patch is
      seen in crickets, which have no comb. Mapping both gene expression patterns and
      morphological characters onto the insect phylogenetic tree demonstrates that in
      the cases of wing suppression and comb formation the appearance of expression of
      Scr in the prothorax apparently precedes these specific functions.

PMID- 9006079
TI  - The Drosophila dCREB-A gene is required for dorsal/ventral patterning of the
      larval cuticle.
AB  - We report on the characterization of the first loss-of-function mutation in a
      Drosophila CREB gene, dCREB-A. In the epidermis, dCREB-A is required for
      patterning cuticular structures on both dorsal and ventral surfaces since dCREB-A
      mutant larvae have only lateral structures around the entire circumference of
      each segment. Based on results from epistasis tests with known dorsal/ventral
      patterning genes, we propose that dCREB-A encodes a transcription factor that
      functions near the end of both the DPP- and SPI-signaling cascades to translate
      the corresponding extracellular signals into changes in gene expression. The
      lateralizing phenotype of dCREB-A mutants reveals a much broader function for
      CREB proteins than previously thought.

PMID- 9006080
TI  - Ligand-bound RXR can mediate retinoid signal transduction during embryogenesis.
AB  - Retinoids regulate various aspects of vertebrate development through the action
      of two types of receptors, the retinoic acid receptors (RARs) and the retinoid-X
      receptors (RXRs). Although RXRs bind 9-cis-retinoic acid (9cRA) with high
      affinity, in vitro experiments suggest that RXRs are for the most part not
      liganded, but serve as auxiliary factors forming heterodimers with liganded
      partner receptors such as RAR. Here we have used RXR- and RAR-specific ligands 4
      [1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-napthyl)ethenyl]b enzoic acid
      (LG69) and (E)-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1
      prope nyl]benzoic acid (TTNPB), and show that, in the context of an embryo,
      liganded RXR can mediate retinoid signal transduction. This conclusion emerges
      from examining the induction of several retinoid-responsive genes in the limb bud
      (Hoxb-6/-8, RARbeta) and in the developing central nervous system (Hoxb-1, otx
      2). RARbeta and Hoxb-1 genes were most effectively activated by a combination of
      TTNPB and LG69, suggesting that the activation of these genes benefits from the
      presence of ligand-bound RAR and ligand-bound RXR. Hoxb-6/-8 genes were most
      efficiently induced by LG69, suggesting that liganded RXR can activate these
      genes. The regulation of the expression of the otx-2 gene was complex; expression
      was repressed by TTNPB, but such repression was relieved when LG69 was provided
      together with TTNPB, suggesting that ligand-bound RXR can overcome repression of
      transcription exerted by liganded RAR. Based on these findings, we propose that
      in our experimental system in which ligands are provided exogenously,
      transcriptional regulation of several genes involves liganded RXR.

PMID- 9006081
TI  - Compartmental organization of the Drosophila genital imaginal discs.
AB  - We have investigated the anterior and posterior compartmental organization of the
      genital imaginal disc. Unlike the thoracic discs, the genital disc is a compound
      disc consisting of three primordia--the female genital, male genital, and anal
      primordia. Here we provide evidence that each primordium is divided into anterior
      and posterior compartments. Genes that are known to be expressed in compartment
      specific manners in other discs (engrailed, hedgehog, patched, decapentaplegic,
      wingless and cubitus interruptus) are expressed in analogous patterns in each
      primordium of the genital disc. Specifically, engrailed and cubitus interruptus
      are expressed in complementary domains, while patched, decapentaplegic and
      wingless are expressed along the border between the two domains. Mitotic clones
      induced at the beginning of the second larval instar do not cross the boundary
      between the engrailed-expressing and cubitus interruptus-expressing domains,
      indicating that these domains are true genetic compartments. Furthermore, we
      examined the phenotypes of mutant clones of the cAMP-dependent protein kinase A
      and engrailed-invected, genes that are known to play compartment-specific
      functions in other discs. These experiments demonstrate that the
      anterior/posterior patterning functions of these genes are conserved in the
      genital disc. The adult clonal phenotypes of protein kinase A and engrailed
      invected mutants also provide a more detailed map of the adult genitalia and
      analia with respect to the anterior/posterior compartmental subdivision. Our
      results lead us to propose a new model to describe the anterior and posterior
      compartmental organization of the genital disc.

PMID- 9006082
TI  - Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for
      expression in lens and nasal placode.
AB  - We have identified and mapped three members of a new family of vertebrate genes,
      designated Eya1, Eya2 and Eya3, which share high sequence similarity with the
      Drosophila eyes absent (eya) gene. Comparison of all three murine Eya gene
      products and that encoded by the Drosophila eya gene defines a 271 amino acid
      carboxyl terminal Eya domain, which has been highly conserved during evolution.
      Eya1 and Eya2, which are closely related, are extensively expressed in cranial
      placodes, in the branchial arches and CNS and in complementary or overlapping
      patterns during organogenesis. Eya3 is also expressed in the branchial arches and
      CNS, but lacks cranial placode expression. All three Eya genes are expressed in
      the developing eye. Eyal is expressed in developing anterior chamber structures,
      including the lens placode, the iris and ciliary region and the prospective
      corneal ectoderm. Eyal is also expressed in retinal pigment epithelium and optic
      nerve. Eya2 is expressed in neural retina, sclera and optic nerve sheath.
      Moreover, Eya1 and Eya2 expressions in the lens and nasal placode overlap with
      and depend upon expression of Pax6. The high sequence similarity with Drosophila
      eya, the conserved developmental expression of Eya genes in the eye and the Pax6
      dependence of Eya expression in the lens and nasal placode indicates that these
      genes likely represent functional homologues of the Drosophila eya gene. These
      results suggest that members of the Eya gene family play critical roles
      downstream of Pax genes in specifying placodal identity and support the idea that
      despite enormous morphological differences, the early development of insect and
      mammalian eyes is controlled by a conserved regulatory hierarchy.

PMID- 9006083
TI  - Sperm-egg fusion is the prelude to the initial Ca2+ increase at fertilization in
      the mouse.
AB  - Fusion of sperm and egg plasma membranes is an early and essential event at
      fertilization but it is not known if it plays a part in the signal transduction
      mechanism that leads to the oscillations in the cytoplasmic free Ca2+
      concentration ([Ca2+]i) that accompany mammalian egg activation. We have used two
      independent fluorescence methods and confocal microscopy to show that cytoplasmic
      continuity of egg and sperm precedes the onset of the first [Ca2+]i increase in
      mouse eggs. The Ca2+ indicator dye Ca2+-green dextran was microinjected and its
      transfer from egg to sperm was monitored. We found that it occurred before, and
      without a requirement for, any detectable [Ca2+]i increase in the egg. In
      separate experiments [Ca2+]i changes were recorded in populations of eggs, using
      fura red, and the eggs fixed at various times after some of the eggs had shown a
      [Ca2+]i transient. Fusion of the sperm and egg was then assessed by Hoechst dye
      transfer. All eggs that showed a [Ca2+]i increase had a fused sperm but more than
      half of the eggs contained a sperm but had not undergone a [Ca2+]i increase.
      These data indicate that sperm-egg fusion precedes [Ca2+]i changes and we
      estimate that the elapsed time between sperm-egg fusion and the onset of the
      [Ca2+li oscillations is 1-3 minutes. Finally, sperm-egg fusion was prevented by
      using low pH medium which reversibly prevented [Ca2+]i oscillations in eggs that
      had been inseminated. This was not due to disruption of signalling mechanisms,
      since [Ca2+]i changes still occurred if low pH was applied after the onset of
      oscillations at fertilization. [Ca2+]i changes also occurred in eggs in low pH in
      response to the muscarinic agonist carbachol. These data are consistent with the
      idea that the [Ca2+]i signals that occur in mammalian eggs at fertilization are
      initiated by events that are closely coupled to the fusion of the sperm and egg
      membranes.

PMID- 9006084
TI  - Evolutionary changes of developmental mechanisms in the absence of cell lineage
      alterations during vulva formation in the Diplogastridae (Nematoda).
AB  - The origin of novelty is one of the least understood evolutionary phenomena. One
      approach to study evolutionary novelty comes from developmental biology. During
      developmental cell fate specification of the nematode Pristionchus pacificus
      (Diplogastridae), five cell fates can be distinguished within a group of twelve
      ventral epidermal cells. The differentiation pattern of individual cells includes
      programmed cell death, cell fusion and vulval differentiation after induction by
      the gonad. A cell lineage comparison among species of seven different genera of
      the Diplogastridae indicates that the differentiation pattern of ventral
      epidermal cells is highly conserved. Despite this morphological conservation,
      cell ablation experiments indicate many independent alterations of underlying
      mechanisms of cell fate specification. Cell fusion and individual cell competence
      change during evolution as well as the differentiation property in response to
      inductive signaling. These results suggest that developmental mechanisms, some of
      which are redundantly involved in vulval fate specification of the genetic model
      organism Caenorhabditis elegans, can evolve without concomitant morphological
      change.

PMID- 9006085
TI  - Two nested gonadal inductions of the vulva in nematodes.
AB  - How do intercellular signals that pattern cell fates vary in evolution? During
      nematode vulva development, precursor cells acquire one of three fates in a
      pattern centered around the gonadal anchor cell. Non-vulval fates are at the
      periphery, outer and inner vulval fates are towards the center. In Caenorhabditis
      elegans, the three fates are specified around the same time by an induction by
      the anchor cell and lateral signaling between the vulva precursor cells. We find
      that, in three other nematode species (Panagrolaimus, Oscheius and Rhabditella
      spp.) spanning two families, the centered pattern is obtained by two temporally
      distinct gonadal inductions. The first induction specifies vulval fates; the
      second induction specifies the inner vulval fates in a subset of the precursors'
      daughters. This evolutionary change in the spatiotemporal connectivity of cell
      interactions allows centering of the pattern between two precursors in
      Panagrolaimus.

PMID- 9006086
TI  - p53 induction, cell cycle checkpoints, and apoptosis in DNAPK-deficient scid
      mice.
AB  - The p53 tumor suppressor protein is rapidly induced following treatment of cells
      with agents which cause DNA double strand breaks (dsbs) leading to cell cycle
      arrest and/or apoptosis. Scid mutant mice are defective in repair of DNA dsbs
      which was recently shown to be due to lack of DNA-dependent protein kinase
      (DNAPK) activity. DNAPK is normally activated by DNA dsbs and phosphorylates the
      p53 protein. Here we tested the hypothesis that DNAPK transduces the signal from
      DNA dsbs to p53 induction. P53 protein was properly induced in intestinal crypt
      cells of irradiated scid mice and was functional as detected by the large
      increase in apoptotic cells. P53 induction was prolonged, consistent with DNA
      dsbs as the signal to induce p53. Spontaneous levels of apoptosis were elevated
      suggesting that scid mice are sensitive indicators of spontaneously generated DNA
      dsbs. Primary scid fibroblasts underwent normal G1 and G2 arrest in response to
      doxorubicin. DNAPK is not required for p53 induction, cell cycle arrest, or
      apoptosis after DNA damage.

PMID- 9006087
TI  - 7-Methoxy-2-nitronaphtho[2,1-b]furan (R7000)-induced mutation spectrum in the
      lacI gene of Escherichia coli: influence of SOS mutagenesis.
AB  - The mutagenic specificity of 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), a very
      potent genotoxic 2-nitrofuran, was investigated in the lacI gene of E.coli. To
      analyze the influence of SOS-mutagenesis on R7000-induced mutations, 86 and 84
      LacI- mutants were respectively isolated from umuC+ and umuC strains. Treatment
      of bacteria with increasing concentrations of R7000, affected 2-4 times more the
      survival rate in the umuC context, as compared to umuC+. 80% of all mutations
      occurred primarily at G:C base pairs and were substitution events and single-base
      frameshifts (-1) in the same proportions. The six possible substitution events
      were observed in both strains. In the umuC+ context, they were dominated by G:C-
      >T:A transversions. 38% of substitutions at G:C base pairs occurred in the
      consensus sequence 5'TGGCG3' or 5'TGGC3' where the G was mutated. When umuC was
      deficient G:C-->C:G transversions were mainly observed. The proportions of
      substitution mutations were very similar to those that have been reported for
      apurinic (AP) sites, suggesting strongly that one mechanism for R7000-induced
      mutations is the formation of intermediate abasic sites that serve as a substrate
      for error-prone repair. Single frameshift events consisted essentially of
      deletions of one (G:C) base pair in runs of contiguous G or C residues.
      Frameshift frequency increased with the length of the reiterated sequence,
      suggesting a strand-slippage process. Other mutational classes were recovered to
      a lower extent, including double-base frameshifts and large deletions. In
      addition, 10% of the mutants presented two proximate mutations. Comparison of the
      mutations induced by R7000 in the umuC+/umuC backgrounds suggests an influence of
      the umuC product on strand specificity of R7000-induced mutations, particularly
      in the case of frameshift events.

PMID- 9006088
TI  - Quantitation of early clonal expansion of two mutant 61st codon c-Ha-ras alleles
      in DMBA/TPA treated mouse skin by nested PCR/RFLP.
AB  - It has been hypothesized that tumor promotion in mouse skin involves clonal
      expansion of initiated cells with activated c-Harvey (Ha)-ras oncogene to give
      rise to benign tumors. We have used the two stage mouse skin carcinogenesis model
      using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiator and 12-O
      tetradecanoyl-phorbol-13-acetate (TPA) as the tumor promoter to quantitate the
      number of mutated c-Ha-ras alleles in mouse epidermal DNA. Epidermal samples were
      harvested over a 12-week period before the appearance of papillomas. Three 61st
      codon (i.e. CAA) c-Ha-ras mutations, CTA (T2), CGA (G2) and CAT (T3) were
      quantitated by newly developed nested PCR/RFLP assays. During TPA promotion the
      number of T2 mutant copies showed a progressive increase starting at 4 weeks
      after initiation and the number of T3 mutant alleles showed an increase starting
      at 6 weeks. By 12 weeks after initiation, TPA-promoted mouse epidermis averaged
      approximately 8x10(5) T2 mutant alleles per epidermis while the number of T3
      mutant alleles averaged 3x10(4) per epidermis. The best-fit lines for the
      quantitation of mutant alleles derived from DMBA/TPA-treated mice from 4 to 12
      weeks after initiation were exponential. These results were consistent with
      clonal expansion of epidermal cells carrying these mutations during tumor
      promotion. The slopes of the best-fit lines for the mutant copies indicated a
      trend in which cells with the T2 mutations had a growth advantage during TPA
      promotion over cells with the T3 mutation.

PMID- 9006089
TI  - Characterization of a putative p53 binding site in the promoter of the mouse
      tissue inhibitor of metalloproteinases-3 (TIMP-3) gene: TIMP-3 is not a p53
      target gene.
AB  - We have recently cloned the promoter of the mouse tissue inhibitor of
      metalloproteinases-3 (TIMP-3) gene and have identified a putative p53 binding
      site (5'-GGGCTTGCTT GACGTCCA GAACAGGGTC-3'), which contains two p53 consensus
      binding motifs (bold) with two nucleotide mismatches (underlined) in the second
      motif and an 8 bp spacer in between. Since both p53 and TIMP-3 are involved in
      cell cycle progression, we tested the hypothesis that TIMP-3 is a p53 downstream
      effector gene, mediating p53 activity. A good correlation between p53 protein
      levels and TIMP-3 expression was found among mouse liver cell lines. However,
      when TIMP-3 promoter driven luciferase constructs were tested for p53
      responsiveness in these cells, the construct containing the putative p53 binding
      site did not show significant difference from the one having the p53 site
      deleted. The gel retardation assay showed that the oligo (T3) made from the
      putative p53 binding site in the mouse TIMP-3 promoter did not bind to p53
      protein, nor did an oligo (T3W) with a correction for the two mismatched
      nucleotides in the second motif. When the 8 bp spacer was removed, however, the
      oligo T3WSF (same as the T3W with spacer free) but not T3SF (T3 without spacer)
      binds to p53, indicating that both the spacer between two motifs and consensus
      binding sites determined the p53 binding. It is worth noting that under a less
      stringent assay condition (0.2 microg instead of 1.0 microg of dI/dC), T3SF did
      weakly bind to p53. Lastly, the compounds that induce p53 transactivation
      activity did not induce TIMP-3 expression. We concluded from this study that TIMP
      3 is not a p53 downstream effector gene.

PMID- 9006090
TI  - Organ-specific oxidative DNA damage associated with normal birth in rats.
AB  - Mammalian DNA contains bulky endogenous DNA modifications (I-compounds), which
      increase with age in unexposed animals, as shown by 32P-postlabeling. We have
      examined the perinatal formation of a subclass (type II) of I-compounds in rat
      liver, kidney, skin and lung. These I-compounds represent bulky oxidative DNA
      lesions, defined herein as intrastrand base-base and base-sugar cross-links,
      adducts of lipid peroxidation products and DNA-protein cross-links. We observed a
      rapid increase in the levels of five bulky oxidative DNA lesions during the first
      hours after normal birth of rats, with total levels increasing 4.2-, 3.0- and 1.3
      fold, respectively, in liver, kidney and skin. This effect was not noted in lung.
      The results were consistent with oxidative stress induced by the known sudden
      increase in partial oxygen pressure at birth in blood and tissues, implying
      inadequate antioxidant defenses in the affected neonatal organs. Hepatic
      oxidative damage appeared intensified by increased concentrations of pro-oxidants
      and reduced concentrations of antioxidants in the maternal diet. The postnatal
      DNA lesions are postulated to be premutagenic, as indicated by their bulky nature
      and persistence. Pathophysiological effects of oxidative DNA damage would be
      exacerbated by rapid cell proliferation in neonatal tissues and consequent
      fixation as mutations. In addition to inherited mutations, DNA lesions acquired
      as a consequence of normal birth may play a hitherto unrecognized role in
      spontaneous carcinogenesis and age-related degenerative diseases.

PMID- 9006091
TI  - Involvement of transforming growth factor alpha (TGFalpha) and epidermal growth
      factor receptor (EGFR) in sex hormone-induced prostatic dysplasia and the growth
      of an androgen-independent transplantable carcinoma of the prostate.
AB  - We previously reported the induction of dysplasia, a putative precursor of
      carcinoma, in the dorsolateral prostates (DLPs) of Noble rats by the combined
      administration of testosterone (T) and estradiol-17beta (E2) for 16 weeks.
      Additionally, we demonstrated growth of the AIT, a DLP-derived, androgen
      independent, transplantable solid tumor, in castrated syngeneic hosts. In this
      investigation, using Northern blot hybridization, radioimmunoassays and
      radioligand assays, we showed that transforming growth factor-alpha (TGFalpha)
      and epidermal growth factor receptor (EGFR) were expressed at close to non
      detectable levels in the ventral prostates but at low, but measurable, levels in
      the DLPs of untreated rats. Enhanced expression of this ligand and its receptor
      was detected in the DLPs harboring dysplasia and marked overexpression of these
      molecules was noted in the AIT. In contrast, epidermal growth factor (EGF)
      expression was found to be constitutively expressed, at high levels, in both
      normal and dysplastic DLPs, but virtually absent in the AIT. Immunohistochemical
      data suggested that EGF, TGFalpha and EGFR were aprocine secretory products of
      the normal DLP, with TGFalpha and EGF localized to the supranuclear complexes and
      EGFR to the apical membranes of epithelial cells. Alterations in immunostaining
      patterns for TGFalpha and EGFR were exclusively detected in the dysplastic
      lesions in the DLPs of T + E2-treated rats. Enhanced intracytoplasmic
      localization for both peptides were found to accompany the loss of cell polarity
      in dysplastic foci. Strong intracytoplasmic immunostaining for TGFalpha was
      observed in some AIT cells whilst staining for EGFR was present in the membranes
      of tumor cells that formed psuedoacini. Taken together, our findings suggest that
      autocrine mechanisms may play an important role early in the carcinogenic process
      and that progression to an androgen-independent neoplastic growth may be
      modulated by this signaling pathway.

PMID- 9006092
TI  - Increased levels of cathepsin B and L, urokinase-type plasminogen activator and
      its inhibitor type-1 as an early event in gastric carcinogenesis.
AB  - BACKGROUND: Cysteine proteases [cathepsin B (CATB), cathepsin L (CATL)], the
      serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type
      1 (PAI-1) play an important part in cancer invasion. No data are available on the
      relationship between these proteases and gastric precancerous changes. AIMS: To
      determine CATB, CATL, UPA, PAI-1 in chronic atrophic gastritis, intestinal
      metaplasia and gastric epithelial dysplasia, as precancerous changes, and to
      compare these data with those obtained in gastric cancer. PATIENTS: Endoscopic
      biopsies were obtained from 12 patients with gastric cancer (cancerous tissue),
      33 patients with chronic atrophic gastritis (all with intestinal metaplasia and
      12 with dysplasia) and from 47 control subjects, for a total of 92 patients.
      METHODS: Antigen concentrations were measured using ELISA methods.
      Immunohistochemistry was performed using monoclonal anti-CATB and anti-PAI-1
      antibodies. RESULTS: CATB, CATL, UPA and PAI-1 were significantly higher in
      chronic atrophic gastritis than in controls (CATB: P < 0.001; CATL: P < 0.005;
      UPA: P < 0.000001; PAI-1: P < 0.005). The same was observed for cancer. CATB and
      UPA were significantly higher in chronic atrophic gastritis, with versus without
      dysplasia (P < 0.05). Dysplastic epithelia showed strong immunoreactivity to PAI
      1 and CATB. CONCLUSIONS: Our study demonstrates that cathepsins, UPA and PAI-1
      may have a role not only in the process of cancer invasion, but also in the
      progression of precancerous changes into cancer.

PMID- 9006093
TI  - Short exposures to tunicamycin induce apoptosis in SV40-transformed but not in
      normal human fibroblasts.
AB  - When SV40-transformed fibroblasts (line 90VAVI) were exposed to tunicamycin, an
      inhibitor of N-linked glycosylation, an extensive cell death occured compared
      with untransformed fibroblasts. A considerable cell loss was obtained within 24 h
      after tunicamycin addition, and after 72 h there were hardly any virus
      transformed cells alive. A 2-h pulse treatment with tunicamycin was found to be
      almost as effective as a continuous 48-h treatment in killing the cells. Even
      such a short exposure as 7 min resulted in a drastically decreased cell viability
      (54%). The morphology of the dying tunicamycin-treated 90VAVI cells suggested
      that they were undergoing apoptosis. This was also supported by the appearance of
      nuclear condensation, as assayed by propidium iodide uptake, which was detectable
      within 2 h after tunicamycin addition. Furthermore, analysis of DNA from
      tunicamycin-treated 90VAVI cells by field inversion gel electrophoresis revealed
      DNA degradation into 50 kbp fragments within 2 h, and conventional agarose gel
      electrophoresis showed 'DNA laddering', indicating internucleosomal DNA cleavage,
      detectable after 36 h. Together with the finding that tunicamycin within seconds
      caused an elevation of [Ca2+]i, a well documented early feature of apoptosis in
      many experimental systems, these results strongly suggest that tunicamycin
      induced cell death in 90VAVI is due to apoptosis. The short tunicamycin exposure
      required to trigger cell death in 90VAVI indicates that the apoptotic process is
      irreversibly induced soon after its addition. It seems unlikely that the pool of
      one or several specific N-linked glycoproteins could be depleted during such a
      short period. Instead the overall accumulation of unglycosylated proteins in ER
      might contribute to the apoptotic response in 90VAVI. Tunicamycin also killed and
      induced DNA degradation in the breast cancer cell line MDA-231.

PMID- 9006094
TI  - Increased gene specific repair of cisplatin induced interstrand crosslinks in
      cisplatin resistant cell lines, and studies on carrier ligand specificity.
AB  - Development of resistance to cisplatin in previously treatment-responsive
      malignancies is a major obstacle to successful treatment. Enhanced DNA repair as
      well as enhanced replicative bypass of DNA adducts have been suggested to play a
      role in the development of resistance to cisplatin. However, the relative
      contribution of these mechanisms is unknown. Second generation platinum compounds
      containing the 1,2-diaminocyclohexane (dach) carrier ligand have been of
      particular interest in the studies of resistance mechanisms since they have been
      effective in treatment of cells resistant to cisplatin. We have investigated the
      formation and repair of interstrand crosslinks (ICL) in the mouse leukemia cell
      line L1210/0 and its carrier ligand specific resistant derivatives L1210/DDP and
      L1210/DACH after treatment with ethylenediamine (en)-Pt and diaminocyclohexane
      (dach)-Pt compounds. ICL in the overall genome were examined using a modification
      of the alkaline elution assay. A Southern blot technique was employed for the
      study of ICL in specific regions of the genome. In the overall genome we found
      decreased formation of ICL with either -en or -dach carrier ligands in the two
      resistant cell lines without carrier ligand specificity. Some carrier ligand
      specificity of ICL formation was observed in the dihydrofolate reductase (DHFR)
      gene, but it did not correlate with the carrier ligand specificity of resistance.
      At the level of the overall genome there was no difference in repair of ICL
      between the sensitive and the two resistant cell lines. When measured in the DHFR
      gene, however, there was enhanced repair of ICL in the two resistant cell lines
      compared with the sensitive cell line. The enhanced repair at the level of the
      gene did not display any carrier ligand specificity.

PMID- 9006097
TI  - Phorbol ester effects on splenic lymphocyte composition and cytotoxic T cell
      activities of SSIN mice: a strain deficient in CD8+ T cells.
AB  - SSIN mice are considerably more sensitive to the effects of 12-O
      tetradecanoylphorbol-13-acetate (TPA) in two-stage skin carcinogenesis protocols
      than are most other strains and stocks of mice. Experiments were performed to
      determine whether there was an immunological basis for this sensitivity. SSIN
      mice were haplotyped and found to be H-2q. T cells represented approximately 31%
      of the splenic cellularity of non-treated SSIN mice, but approximately 44% in
      BALB/c, C57BL/6, B6C3F1 and SENCAR mice. Splenic CD4+/CD8+ T cell ratios were
      approximately 4.2, 2.9, 2.4, 1.8 and 1.7 in SSIN, SENCAR, BALB/c, B6C3F1 and
      C57BL/6 mice, respectively. The unusually high ratio in SSIN spleens was the
      consequence of reductions in CD8+ T cells. The ratio of CD4+/CD8+ T cells in SSIN
      thymocytes was similiar to that measured in the spleen. The splenic cytotoxic T
      lymphocyte (CTL) activities of the various murine strains inversely correlated
      with their splenic CD4+/CD8+ ratios and their sensitivities in two-stage skin
      carcinogenesis protocols. Repeated in vivo topical treatment of SSIN mice with
      TPA caused significant decreases in splenic T cell contents, but affected neither
      the splenic CD4+/CD8+ T cell ratio nor the development of a CTL response upon
      allogeneic tumor challenge. SSIN mice also had very low splenic natural killer
      cell activities. Furthermore, relative to the other strains of mice, SSIN mice
      were poor responders upon alloantigen challenge in mixed lymphocyte response
      assays. These findings demonstrate that SSIN mice differ markedly from other
      murine stocks and strains in their splenic lymphocyte composition and in their
      abilities to mount some MHC-restricted and non-restricted immunosurveillance
      processes.

PMID- 9006096
TI  - Isolation and characterization of a novel gene induced by 2,3,7,8
      tetrachlorodibenzo-p-dioxin in rat liver.
AB  - The differential display technique was used to identify genes whose expression
      was regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of a
      novel sequence was up-regulated in a dose-dependent fashion in liver of Sprague
      Dawley male rats exposed to both chronic and acute treatment with TCDD, as
      measured by densitometry of Northern blot analyses (P < 0.01). A rapid
      amplification of cDNA ends (RACE) procedure was used to isolate a 1.8 kb cDNA
      from a rat liver cDNA preparation. This cloned cDNA, called 25-Dx, was sequenced
      and found to encode a peptide of 223 amino acids. In control rats, the 25-Dx gene
      was expressed at high levels in lung and liver. A hydrophobic domain of 14
      residues followed by a proline-rich domain, both located in the N-terminal
      region, showed 71% homology with the transmembrane domain of the precursor for
      the interleukin-6 receptor and a conserved consensus sequence found in the
      cytokine/growth factor/prolactin receptor superfamily respectively.

PMID- 9006095
TI  - Absence of p16/MTS1 gene mutations in human prostate cancer.
AB  - The tumor suppressor gene p16/MTS1, located on chromosome 9p21, is a cell cycle
      regulatory gene which is frequently altered in human cancers. The role of this
      gene in prostate cancer is unknown. To determine the frequency of deletions and
      point mutations of p16/MTS1 in human prostate cancer, we examined 18 cancer and
      matched benign and hyperplastic tissue specimens. Deletions of p16/MTS1 were
      detected by semi-quantitative multiplex polymerase chain reaction in which a
      portion of exon 2 of the p16/MTS1 gene and a control marker, the glyceraldehyde 3
      phosphate dehydrogenase gene, were amplified simultaneously. 'Cold' single
      stranded conformational polymorphism (SSCP) analysis was performed to examine
      exons 1 and 2 of the p16/MTS1 gene for point mutations. Our data indicate no
      evidence for intragenic homozygous deletion in the prostate tumors. One prostate
      tumor and matched benign tissue showed mobility shifts. Direct DNA sequencing of
      the SSCP positive samples showed a G --> A transition in codon 140 which would
      result in an amino acid change from alanine to threonine. Our results indicate
      that deletions and point mutations in the p16/MTS1 gene are rare and do not play
      a major role in human prostate carcinogenesis.

PMID- 9006098
TI  - Variant mutational activation of the K-ras oncogene in renal mesenchymal tumors
      induced in newborn F344 rats by methyl(methoxymethyl)nitrosamine.
AB  - Renal mesenchymal tumors were induced at high incidence in F344 rats by a single
      intraperitoneal injection of methyl(methoxymethyl)nitrosamine (DMN-OMe) within 48
      h after birth. DNAs from 18 of 35 mesenchymal tumors contained transforming ras
      sequences in NIH3T3 transfection assays: K-ras (17/18) or N-ras (1/18). Single
      stranded conformational polymorphism analysis or dideoxy sequencing of polymerase
      chain reaction-amplified K-ras gene fragments revealed that these neoplasms
      contained a variety of activating mutations in the K-ras oncogene. Alterations in
      codon 12 predominated and included GGT --> GAT transitions, GGT --> GTT or TGT
      transversions, and previously reported insertion mutations, although some tumors
      expressed more than one mutation and the pattern of mutations even varied within
      tumors. Mutations were also found in exons 2 and 3. In addition, tumor
      transplantability into syngeneic hosts correlated positively and significantly
      with K-ras activation. Renal mesenchymal tumors with transforming mutations in
      exon 1 were often successfully passaged (10/12) while tumors which lacked
      mutations in exon 1 were infrequently transplantable (2/14). While the observed
      base substitutions in K-ras are consistent with adduct formation, the presence of
      insertion mutations and intratumor heterogeneity of alterations suggest that ras
      activation in DMN-OMe-induced tumors is not necessarily an early event in
      tumorigenesis.

PMID- 9006099
TI  - Telomerase activation during the linear evolution of human fibroblasts to
      tumorigenicity in nude mice.
AB  - The ribonucleoprotein enzyme telomerase is active in most immortal cell lines,
      most tumors and all tumor-derived cell lines. The enzyme is important because it
      prevents continual shortening of telomeres and therefore plays a significant role
      in chromosome maintenance. In man, telomerase is not active in most somal cells
      with finite lifespans. Using the SV40 T antigen we immortalized and transformed
      to fully tumorigenic a human fibroblast cell strain. We wished to determine when
      telomerase was activated during this progression to tumorigenicity. Using the PCR
      based TRAP assay we found that eight of eight immortal cell lines that were
      either not tumorigenic or rarely formed tumors were telomerase positive at the
      time of inoculation. Additionally, 10 of 11 newly immortal cell lines contained
      telomerase activity within the first 25-33 population doublings after crisis.
      None of the precrisis cells from which these immortal cells were derived were
      positive for telomerase activity. Thus we found that telomerase activation is not
      the final in vivo step in the transformation of these cells and the window of
      activation is usually near the escape from crisis or M2. These results strengthen
      the hypothesis that telomerase activation may allow the rare cell to escape from
      crisis in those immortal cell populations dependent on telomerase for telomere
      maintenance.

PMID- 9006100
TI  - Ha-rasVal12 but not p53Ser247 leads to a significant neoplastic transformation
      rate of the putative rat liver stem cells (oval cell).
AB  - In order to test the controversially discussed hypothesis that oval cells are
      part of a liver stem cell compartment and can give rise to cholangiocellular as
      well as hepatocellular carcinomas in the course of liver carcinogenesis, we
      transfected an oval cell line established in our laboratory with an oncogenically
      activated genomic Ha-ras clone (pUC EJ 6.6), carrying a valine at position 12
      instead of the wild-type glycine, or a rat p53 cDNA mutated by site-directed
      mutagenesis at codon 247, which corresponds to codon 249 in the human p53. This
      codon is of particular interest since it represents a mutation hotspot observed
      in hepatocellular carcinoma especially in regions with high aflatoxin B1
      exposure. Independent Ha-rasVal12 and p53Ser247 recombinant clones were
      subcutaneously injected into syngeneic newborn rats and the resulting tumours
      were analysed histopathologically. Each of two p53Ser247 clones gave negligible
      tumour yields (one tumour out of 13 injected animals), whereas each of two Ha
      rasVal12 clones gave marked tumour yields (four tumours out of 13 and seven out
      of 12 treated animals, respectively). In addition, the p53Ser247-induced tumours
      appeared only after 11 months and were small, whereas the Ha-rasVal12-induced
      tumours appeared already after 6-8 weeks and grew rapidly. Histopathological
      analysis of the tumours revealed only undifferentiated carcinomas. Interestingly,
      one tumour that arose upon injection of Ha-rasVal12-transfected cells stained
      positive for albumin, showing at least a partial hepatocytic differentiation.

PMID- 9006101
TI  - Chemoprevention of radiation-induced mammary tumors in rats by bezafibrate
      administered together with diethylstilbestrol as a promoter.
AB  - Pregnant Wistar-MS strain rats were irradiated with 2.6 Gy of gamma-rays at day
      20 of pregnancy. Rats in the control group (n = 48) were then implanted with a
      diethylstilbestrol (DES) pellet at 35 days after weaning, while being fed a
      control (MB-1) diet. The incidence of mammary tumors was 89.6% within 1 year. In
      the experimental group (n = 22), a bezafibrate (0.15%) diet was initiated
      immediately after weaning, and 35 days after weaning a DES pellet was implanted.
      Administration of dietary bezafibrate together with DES-implantation continued
      for a period of 1 year, at which time the experiment was terminated. The
      incidence (27.3%) of the mammary tumors in the bezafibrate-fed rats was less than
      one-third of that in the control rats. Compared with the control group, the
      number of mammary tumors per tumor-bearing rat in the bezafibrate-treated group
      was reduced. For clarification of the mechanism of the chemopreventive effects of
      bezafibrate, lipid and hormone concentrations in serum were measured. Bezafibrate
      fed rats showed a significant decrease in serum prolactin (56%) and triglyceride
      (63%) concentrations, and a significant increase in serum estradiol-17beta (3.8
      fold), cholesterol ester (2.0-fold) and TSH (2.0-fold) concentrations in
      comparison with the control rats. The bezafibrate diet inhibited the formation of
      DES-induced pituitary tumors. However, the development of mammary glands in the
      bezafibrate-fed rats was stimulated more than that in the control rats treated
      with DES alone. The present results demonstrate that bezafibrate is effective in
      preventing mammary tumors induced by radiation together with DES, possibly by
      reducing prolactin and triglyceride concentrations.

PMID- 9006102
TI  - Hprt mutations in human T-lymphocytes reflect radioprotective effects of the
      aminothiol, WR-1065.
AB  - Aminothiols such as WR-2721 and its active free thiol WR-1065 have previously
      been shown to reduce mutations resulting from ionizing radiation in exponentially
      growing cells. In this study, non-dividing human G0 T-lymphocytes were exposed to
      the aminothiol radioprotective agent, WR-1065, 30 min before or 3 h after
      external beam gamma-irradiation and subsequently assessed for survival and
      mutation induction at the hprt locus. Cytotoxicity due to gamma-irradiation was
      reduced only when the WR-1065 was present during irradiation. The frequency of
      hprt mutations, however, was reduced regardless of time of administration,
      although the reduction was statistically significant only when WR-1065 was added
      30 min before irradiation (P < 0.01). This is the first study to demonstrate the
      protective effects of WR-1065 against radiation-induced mutation in a reporter
      gene using a human non-cycling cell. Hprt mutations arising in vivo in these
      cells may be useful for monitoring the radioprotective effect of aminothiols in
      human populations.

PMID- 9006103
TI  - Monitoring of exposure to acrylonitrile by determination of N-(2
      cyanoethyl)valine at the N-terminal position of haemoglobin.
AB  - A selected ion monitoring gas chromatography-mass spectrometry (GC-MS) procedure
      was developed to determine the interaction product formed by acrylonitrile (ACN)
      with the N-terminal amino group in haemoglobin. The product, N-(2
      cyanoethyl)valine (CEV), was analysed following its release from the protein by a
      modified Edman degradation procedure. Quantitation was achieved using N-(2
      cyanoethyl)-[2H8]Val-Leu-Ser as internal standard. The limit of detection of the
      assay was 1 pmol CEV/g globin. A close to linear dose-response relationship was
      found for adduct formation in rats treated with ACN by gavage. On the basis of a
      linear extrapolation, a dose of 1 mg/kg body wt yielded 248 pmol CEV/g globin.
      Two groups of workers who were exposed to ACN contained 1984 +/- SD 2066 (n = 9)
      and 2276 +/- SD 1338 (n = 7) pmol CEV/g globin respectively. These values were
      highly significantly greater (P < 0.01 following a one-way analysis of variance
      with a logarithmic transformation of the data) than those in a group of control
      workers in the same factory (31.1 +/- SD 18.5 pmol CEV/g globin, n = 11). The
      concentrations of N-terminal CEV in globin samples from 13 smoking and 10 non
      smoking mothers and from their newborns were determined. Adduct levels in the
      smokers averaged 217 +/- 85.1 pmol CEV/g globin, significantly higher than the
      levels in non-smokers, which were undetectable. Individual values in the mothers
      were very highly correlated with the levels in their babies (which averaged 99.5
      +/- 53.8 pmol CEV/g globin), which demonstrates that transplacental transfer of
      ACN occurs. Significant correlations were also found between the number of
      cigarettes smoked per day by the mother and the CEV levels in both the mothers'
      and newborns' globin. There was, however, no correlation between the CEV levels
      and those of the ethylene oxide adduct N-(2-hydroxyethyl)valine in samples from
      either the mothers or babies.

PMID- 9006105
TI  - Adduct formation on DNA and haemoglobin in mice intraperitoneally administered
      with styrene.
AB  - Styrene-specific N-7- and O6-guanine DNA adducts and N-terminal valine adducts
      were determined in mice tissues after the intraperitoneal administration of
      styrene. Blood, liver, lungs and spleen were collected 3 h after administration
      of various doses (from 0 to 4.35 mmol/kg b.w.) of styrene. DNA adducts were
      analysed by the modified 32P-postlabelling assay and N-terminal valine adducts
      were detected by GC-MS according to the modified Edman degradation technique. In
      the dose-range studied, for all adducts a clear dose-response relationship was
      observed. 7-Alkylguanines and O6-styrene guanine adducts were most abundant in
      lungs, approximately 30% more than in liver and spleen. In all analysed tissues 7
      alkylguanines were more abundant than O6-styrene guanine adducts. We found a
      considerably lower rate of N-terminal valine adduct formation as compared with
      both DNA adducts. The ratio between 7-alkylguanines and O6-guanine adducts was
      1.9, 1.6 and 7.8 in liver, lung and spleen, respectively. In vitro determination
      of both DNA adducts by 32P-postlabelling resulted also in a lower ratio than that
      reported earlier using an HPLC analysis. All correlation's between dose,
      haemoglobin and DNA adducts were very high and significant. However, at the
      highest injected doses the adduct formation showed a levelling off. To explain
      this phenomenon a model simulation was performed revealing that 3 h after the
      injection of the higher doses styrene was not completely converted into styrene
      7,8-oxide.

PMID- 9006104
TI  - Structural characterization by mass spectrometry of hemoglobin adducts formed
      after in vivo exposure to methyl bromide.
AB  - A mass spectrometric procedure is described for the structural study of the
      adducts formed in human hemoglobin by in vitro exposure of erythrocytes to the
      alkylating agent methyl bromide using different protein to reagent ratios.
      Peptide mapping by HPLC and tandem mass spectrometry allowed location of
      methylated amino acids within the protein sequence. A prominent reactivity of
      several nucleophilic side chains in human hemoglobin subunits was observed, which
      was modulated by the concentration of the alkylating agent. Cysteine residues,
      the main reactive sites, were fully methylated in hemoglobin exposed to a 10-fold
      excess of methyl bromide, differently from other residues, including histidines,
      showing a heterogeneous pattern of methylation that was largely directed by their
      environment. No evidence of methylation was found at the heme proximal histidines
      beta92 and alpha87. A more selective methylation was obtained when the ratio
      methyl bromide: hemoglobin was lowered to about 1:1. In this last case only
      specific residues were reactive. Among them, the N-terminal amino group of both
      alpha- and beta-globins, cysteine 104 in the alpha-chain and cysteine 93 (not
      cysteine 112) in the beta-chain, indicating a different accessibility to reaction
      of the sulfhydryl groups on the protein chain. Thus hemoglobin side chains are
      selectively modified and the degree of modification at each site is a function of
      the position of the single amino acid residue within the protein quaternary
      structure, raising the possibility that alterations of structure and functional
      properties of human hemoglobin following exposure to alkylating agents may be
      mediated through such covalent protein modifications. The results obtained
      demonstrate the usefulness of the analytical approach for the characterization of
      hemoglobin adducts with methyl bromide or similar compounds, which can constitute
      the basis for biomonitoring of human exposure.

PMID- 9006106
TI  - Exposure to 60 Hz magnetic fields does not alter clinical progression of LGL
      leukemia in Fischer rats.
AB  - Associations between exposure to 60-Hz magnetic fields in residential and
      occupational environments and the incidence of leukemia and other cancers has
      been suggested by the results of a number of epidemiology studies. To address
      these potential associations, a study has been conducted to determine if 60-Hz
      magnetic fields can alter the clinical progression of leukemia. In the large
      granular lymphocytic (LGL) leukemia model, spleen cells from aged leukemic rats
      were transplanted into young, male Fischer 344 rats, producing leukemia in a
      relatively short period. A total of 72 animals were randomly assigned to four
      treatment groups (18/group) as follows: (1) 10 G; (2) sham exposed (null
      energized field) (approximately 20 mG); (3) ambient controls (<1 mG); and (4)
      positive controls (5 Gy whole body irradiation from Cobalt-60, 4 days before
      initiation of exposure). At the initiation of exposure or sham-exposure, all rats
      were injected (i.p.) with 2.2x10(7) fresh, viable, LGL leukemia cells. The
      magnetic fields were activated for 20 h per day, 7 days per week; all exposure
      conditions were superimposed over the natural ambient magnetic field. Eighteen
      rats from each treatment were bled at weeks 0, 2, 4, 5, 6, 7, 8 and 10 to
      monitor, in the same set of animals, the clinical progression of the LGL disease
      and survival of the animals. Peripheral blood hematological changes were
      monitored to evaluate the progression of the leukemia. In general, no significant
      or consistent differences were detected between the magnetic field exposed and
      the ambient field control groups, although some inconsistent and random
      differences were occasionally observed. These data indicate that the 10 G
      magnetic fields did not significantly alter the clinical progression of LGL
      leukemia in Fischer 344 rats.

PMID- 9006107
TI  - Absence of mutations in the p53 tumor suppressor gene in woodchuck hepatocellular
      carcinomas associated with hepadnavirus infection and intake of aflatoxin B1.
AB  - Infection with hepadnaviruses and exposure to aflatoxin B1 (AFB1) are considered
      major risk factors in the development of hepatocellular carcinoma (HCC) in humans
      and in animals. A high rate of mutations in the p53 tumor suppressor gene in
      hepatocellular carcinomas of predominantly hepatitis B virus (HBV) carrier
      patients has been recently related to dietary aflatoxin. Another member of the
      hepadnavirus family, the woodchuck hepatitis virus (WHV), infects woodchucks in a
      manner similar to that of HBV in humans. Therefore, it was of particular interest
      to determine whether the p53 gene in woodchuck HCCs associated with hepadnavirus
      infection and with exposure to AFB1 is affected in the same manner as in human
      HCCs. By direct PCR-sequencing, we analyzed exons 4-9 of the p53 gene in 13 HCCs
      from 12 woodchucks (two uninfected, ten WHV carriers). Six WHV carrier and two
      uninfected woodchucks were treated with AFB1. None of the analyzed HCC samples
      exhibited mutations, either in p53 gene exons 4-9, or in splicing donor-acceptor
      sites. The present data are consistent with our previous study that indicated a
      low rate of p53 mutations in HCCs of AFB1-treated ground squirrels, either
      infected or not infected with ground squirrel hepatitis virus, and in WHV carrier
      woodchucks not exposed to AFB1. Overall, our findings indicate that in woodchucks
      and in ground squirrels exposure to aflatoxin may affect the development of p53
      mutations less than in humans.

PMID- 9006108
TI  - Effect of nuclear environment on the distribution of benzo[a]pyrene diol epoxide
      induced adducts in the HPRT gene of human fibroblasts.
AB  - (+/-)-7beta,8alpha- Dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]py
      rene (BPDE) is the principal reactive metabolite of the carcinogenic
      environmental pollutant benzo[a]pyrene. Intensive studies of the distribution of
      BPDE-induced adduct formation in chromatin DNA compared to that in protein-free
      DNA have been conducted. However, until recently, investigation of BPDE-induced
      adduct formation at the nucleotide level in intact mammalian cells has not been
      feasible. We used ligation-mediated polymerase chain reaction (LMPCR) in
      conjunction with Escherichia coli UvrABC excinuclease to investigate the
      distribution of BPDE-induced adducts in the non-transcribed strand of exon 3 of
      the HPRT gene in normal human fibroblasts at the level of individual nucleotides
      to single nucleotide resolution using synchronized cell populations. We found
      that the relative distribution of BPDE adducts in the region of interest was
      essentially the same in cells treated in early G1 phase, S-phase, late G2/M
      phase, and in cells blocked at metaphase. Furthermore, for almost all nucleotide
      positions, the relative distribution of BPDE adducts in the intact cells was very
      similar to that found when purified DNA was treated with BPDE in vitro. The only
      exception was that in vivo, adduct formation at a region of six consecutive
      guanines, i.e. nucleotides 207-212, was strongly enhanced compared with that seen
      with DNA treated in vitro. No obvious nucleosomal structures or other protein-DNA
      interaction were detected within the region of interest by in vivo footprinting
      with micrococcal nuclease and other reagents revealed. In vitro studies mapping
      BPDE-induced adduct formation using Sequenase and UvrABC excinuclease suggested
      that this region of six consecutive guanines adopts a special DNA conformation.
      Therefore, we conclude that rather than reflecting protein-DNA interaction, the
      enhanced BPDE-induced adduct formation at nucleotides 207-212 in vivo reflects
      the impact of the physiological environment in the cell nucleus on the local DNA
      conformation, and that this effect remains constant throughout the cell cycle.

PMID- 9006110
TI  - Changes in methyl-sensitive restriction sites of liver DNA from hamsters
      chronically exposed to hydrazine sulfate.
AB  - Hydrazine sulfate is a genotoxic hepatocarcinogen for the hamster. A study was
      conducted to follow changes in DNA maintenance methylation in selected genes in
      liver DNA during the 21-month induction of liver adenomas and hepatocellular
      carcinomas by demonstrating changes in restriction fragment length polymorphism.
      Male Syrian golden hamsters were exposed to hydrazine sulfate in the drinking
      water at three concentrations (170, 340 and 510 mg/l) shown previously to result
      in a dose-dependent induction of liver tumors. Liver DNA from animals exposed to
      the high concentration for 6, 12, 16, 20 and 21 months and animals exposed to the
      low or mid concentration for 21 months was digested with EcoRI, MspI, HindIII or
      BamHI, or a combination of one of these endonucleases and a methyl-sensitive
      restriction enzyme, HpaII or HhaI. The DNA digests were subjected to Southern
      analysis using a c-DNA probe for one of the following genes: DNA
      methyltransferase (DMT), c-Ha-ras, c-jun, c-fos, and c-myc proto-oncogenes, p53
      tumor suppressor gene or gamma-glutamyltranspeptidase. Alteration in DNA
      restriction by methyl-sensitive endonucleases was detected in four (DMT, c-Ha
      ras, p53 and c-jun) of the seven genes examined and as early as 6 months in
      animals exposed to the highest concentration of hydrazine sulfate; alteration of
      recognition sites in c-Ha-ras was also detected in DNA from animals exposed for
      21 months to the intermediate concentration of hydrazine sulfate. Early changes
      in recognition sites, presumed to indicate altered methylation status of DNA
      cytosine and/or guanine mutations, were seen using c-DNA probes for DMT, c-Ha-ras
      and c-jun; in the p53 tumor suppressor gene alteration of such sites was a late
      event relevant to appearance of liver adenomas and hepatocellular carcinomas.
      Evidence for hypomethylation in the p53 and c-jun genes and hypermethylation of
      the c-Ha-ras and DMT genes is provided. This study supports the induction of site
      specific hypomethylation and hypermethylation during the course of hydrazine
      carcinogenesis.

PMID- 9006109
TI  - Methylation status of DNA cytosine during the course of induction of liver cancer
      in hamsters by hydrazine sulfate.
AB  - Hydrazine, which is toxic and carcinogenic to rodent liver, has been shown to
      react with endogenous formaldehyde in the liver to form formaldehyde hydrazone
      (CH2 = N-NH2), an alkylating intermediate that methylates DNA guanine at the N7-
      and O6-positions. Studies were conducted to investigate the role of chronic
      hydrazine-induced hepatotoxicity on DNA maintenance methylation (formation of 5
      methyldeoxycytosine) and the development of liver cancer. Male Syrian golden
      hamsters were given hydrazine sulfate (0, 170, 340 and 510 mg/l) in drinking
      water for 21 months (average dose 0, 4.2, 6.7 and 9.8 mg/kg body wt hydrazine as
      the free base). Hepatotoxicity was evaluated histologically, and regenerative DNA
      synthesis and maintenance methylation were measured as the incorporation of
      [methyl-14C]thymidine into DNA and the methyl moiety of [methyl-3H]methionine
      into 5-methyldeoxycytosine in DNA, respectively. Methylguanines were detected in
      liver DNA at the first observation time of 6 months of treatment; levels of these
      aberrant bases decreased or became undetectable at 14 months, and increased in a
      dose-related manner for the remainder of the study. DNA adducts persisted in the
      highest dose group throughout the study, repeating the results of a similar study
      previously reported by this laboratory (Bosan et al., Carcinogenesis, 8, 439-444,
      1987). Linear regression analysis of thymidine and methionine methyl moiety
      incorporation into liver DNA suggested impairment of maintenance methylation of
      DNA (5-methyldeoxycytosine) in the middle and high exposure animals. Hepatic
      adenomas and hepatocellular carcinomas developed in a dose-related manner and
      were highly correlated to decreased uptake of radiolabel from methionine into DNA
      5-methylcytosine. These results are part of a continuing study on alteration of
      maintenance methylation during hydrazine induction of liver cancer.

PMID- 9006111
TI  - Asbestos promotes morphological transformation and elevates expression of a gene
      family invariably induced by tumor promoters in C3H/10T1/2 cells.
AB  - The murine proliferin gene family, which has been shown to respond consistently
      to tumor promoters and other cellular pro-oxidant agents in C3H/10T1/2 cells, was
      used to monitor responses after treatment of these cell cultures with toxic, pro
      oxidant asbestos fibres. Proliferin mRNA levels were increased by amosite,
      crocidolite or chrysotile asbestos fibres, especially in the presence of fresh
      serum and at low cell densities. Promotion of morphological transformation was
      confirmed in two-stage focus formation assays using crocidolite at a fibre
      density that induced proliferin expression. Asbestos-induced gene expression was
      inhibited by millimolar levels of N-acetylcysteine (NAC), supporting a linkage
      between: (i) induced oxidant stress that was sufficient to promote morphological
      transformation; (ii) induction of proliferin expression. Other anti-oxidant
      compounds (dithiothreitol and pyrrolidine dithiocarbamate) or enzymes (superoxide
      dismutase and catalase) did not inhibit induced expression. Non-fibrous powders
      (titanium dioxide, quartz or silica gel) were also effective inducers of
      proliferin mRNA accumulation. Latex beads and activated charcoal were effective
      at higher particle densities, implying that ubiquitous particle-induced surface
      membrane effects can lead to an NAC-reversible step necessary for proliferin
      induction. The results showed that asbestos resembled all other promoters of
      morphological transformation in C3H/10T1/2 cells in that an antioxidant-sensitive
      induction of the proliferin gene family occurred following treatment.

PMID- 9006112
TI  - Characterization of the major DNA adduct formed by the food mutagen 2-amino-3
      methyl-9H-pyrido[2,3-b]indole (MeAalphaC) in primary rat hepatocytes.
AB  - Cooking of proteinous food results in the formation of heterocyclic amines. Among
      these, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) has been identified as
      a mutagenic pyrolysis product of soya protein and has been detected in grilled or
      pan fried meat. It was subsequently proven to be carcinogenic in mice and,
      recently, in rats and to form covalent DNA adducts in vitro and in vivo. The
      corresponding nitro compound, 2-nitro-3-methyl-9H-pyrido[2,3-b]indole
      (MeNalphaC), was prepared and shown to be a direct acting mutagen in the Ames
      Salmonella reversion assay. When MeNalphaC was chemically reduced in the presence
      of DNA a major DNA adduct was detected using the 32P-postlabelling assay. This
      major adduct was characterized by UV spectroscopy and mass spectrometry as N
      (deoxyguanosin-8-yl)-2-amino-3-methyl-9H-pyrido[2,3-b]indole. This structure was
      corroborated by identification of the modified base as a guanine moiety modified
      at the C8 position as judged by chromatographic and spectral comparison with a
      standard synthesized from acetylated guanine-N3-oxide and MeAalphaC was
      characterized by UV/Vis and 1H NMR spectroscopy and mass spectrometry. Treatment
      of primary rat hepatocytes with MeAalphaC (100 microM, 24 h) resulted in adduct
      levels of 9.8 fmol/microg DNA as determined by 32P-postlabelling analysis. Using
      HPLC analysis, two major 32P-labelled adducts were observed accounting for 80 and
      13% of total binding respectively. The major adduct was chromatographically
      indistinguishable from the synthetic deoxyguanosine-C8 adduct using both ion
      exchange thin layer or reversed-phase HPLC. Although MeAalphaC is formed only in
      low p.p.b. levels in cooked food, the contribution to the human carcinogenic risk
      that might be imposed by heterocyclic amines is not to be neglected.

PMID- 9006113
TI  - Copper-mediated DNA damage by metabolites of p-dichlorobenzene.
AB  - p-Dichlorobenzene (p-DCB) has been reported to be carcinogenic for rodents,
      although it does not seem to be mutagenic in bacterial test systems. In this
      study, the mechanism of DNA damage by metabolites of p-DCB in the presence of
      metals was investigated by a DNA sequencing technique using 32P-labeled DNA
      fragments and by an electrochemical detector coupled to an HPLC. 2,5
      Dichlorohydroquinone (DCHQ), one of the major metabolites, caused DNA damage in
      the presence of Cu(II). 2,5-Dichloro-p-benzoquinone (DCBQ) slightly induced DNA
      damage in the presence of Cu(II), but addition of NADH induced DNA damage very
      efficiently. DCHQ plus Cu(II) induced piperidine-labile sites at thymine residues
      at high frequency. A similar DNA cleavage pattern was observed with DCBQ plus
      Cu(II) in the presence of NADH. Both DCHQ and DCBQ plus NADH increased 8-oxo-7,8
      dihydro-2'-deoxyguanosine in calf thymus DNA in the presence of Cu(II). Typical
      hydroxyl radical scavengers showed no inhibitory effects on this Cu(II)-mediated
      DNA damage. Bathocuproine and catalase inhibited the DNA damage, indicating the
      participation of Cu(I) and hydrogen peroxide (H2O2) in the DNA damage. UV-visible
      and ESR spectroscopy has demonstrated that DCHQ is rapidly autoxidized to DCBQ
      via a semiquinone radical, even in the absence of metal ions, indicating that the
      semiquinone radical itself is not the main active species inducing DNA damage.
      These results suggest that a semiquinone radical produced by autoxidation of DCHQ
      and/or reduction of DCBQ by NADH reacts with O2 to form superoxide and
      subsequently H2O2. Consequently, it is considered that the active species derived
      from the reaction of H2O2 with Cu(I) participates in the DNA damage.

PMID- 9006114
TI  - Transplacental mutagenicity of cisplatin: H-ras codon 12 and 13 mutations in skin
      tumors of SENCAR mice.
AB  - Cisplatin is an anticancer agent sometimes used in pregnant women. It is also a
      potent initiator of skin tumors in mice when administered transplacentally. For
      characterization of the transplacental mutagenicity of cisplatin, tumors
      initiated in fetal skin by cisplatin or 7,12-dimethylbenz[a]anthracene (DMBA) and
      promoted by postnatal 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were analyzed
      for H-ras mutations by 'cold' single-strand conformation polymorphism analysis
      and direct sequencing. The expected high incidence of exon II codon 61 mutations
      (20/20) was found in transplacental DMBA-initiated tumors, with no exon I change.
      By contrast, 6/10 cisplatin tumors had seven mutations in codons 12 or 13 of exon
      I, all at GpG dinucleotides. Four of these were unique codon 13 GGC --> GTC
      changes, significantly different from the DMBA group and from historical TPA-only
      controls. The activation of codons 12 and 13 by cisplatin is in accord with the
      known in vitro preference of cisplatin for GpG sites for intrastrand cross
      linking adduct formation. These results provide the first evidence that cisplatin
      can act transplacentally to cause specific mutations in fetal skin that are not
      seen in skin tumors caused by treatment of adult skin with this agent. This is
      evidence for unique molecular fetal carcinogenic pathways and underscores concern
      about human fetal risk due to maternal cisplatin treatment.

PMID- 9006115
TI  - Site-specific modification of the human N-ras proto-oncogene with each diol
      epoxide metabolite of benzo[a]pyrene and thermal denaturation studies of the
      adducted duplexes.
AB  - The central adenine residue (A) of codon 61 in the human N-ras proto-oncogene, 5'
      CGGACAAGAAG-3', has been modified with each enantiomer of the series 1 (DE-1,
      syn) and series 2 (DE-2, anti) benzo[a]pyrene diol epoxide through total chemical
      synthesis. The resulting DNA adducts correspond to a trans ring-opening of the
      oxiranes at the C-10 position of the hydrocarbon by the exocyclic amino group of
      the purine (the relative stereochemistry between the C-9 and C-10 substituents is
      trans). The synthesis involved coupling of 6-fluoro-9-(2-deoxy-beta-D-erythro
      pentofuranosyl)purine with the racemic aminotribenzoates derived from each diol
      epoxide. The resulting pairs of diastereomeric adducts were converted to the 5'-O
      DMT 3'-O-phosphoramidites and incorporated into the DNA sequence through a
      partially automated procedure. Resolution of the diastereomeric oligomers
      resulting from each diol epoxide enantiomer was conveniently achieved at the very
      end of the synthesis. This adds simplicity and efficiency to the preparation of
      alkylated oligomers through this route. Thermal denaturation of the modified
      duplexes with a complementary strand, as well as a partially complementary target
      containing a central apurinic site, has been evaluated. These studies indicate
      striking differences in the absorbance-temperature co-operativity when the 345 nm
      pyrene absorption is monitored. The results of such previously undescribed
      experiments provide a comparison of the physical properties of oligomers that
      differ in the arrangement of substituents in the hydrocarbon moiety, but are
      otherwise identical. We believe that such comparisons between diol epoxide-DNA
      adducts of the same hydrocarbon and those of different hydrocarbons will provide
      information about the orientation of the hydrocarbon moieties relative to the
      adjacent bases. Therefore, these results will be useful parameters in the
      evaluation of structure-activity relationships of diol epoxide-DNA lesions.

PMID- 9006116
TI  - Methyl tertiary butyl ether lacks tumor-promoting activity in N
      nitrosodiethylamine-initiated B6C3F1 female mouse liver.
AB  - Methyl tertiary butyl ether (MTBE) is an additive in some formulations of
      unleaded gasoline (UG) that enhances octane and reduces carbon monoxide emissions
      from motor vehicles. MTBE in CD-1 mice and UG in B6C3F1 mice increased the
      incidence of liver tumors selectively in female mice in their chronic bioassays.
      Both agents were negative in in vitro tests of genotoxicity, and exhibit similar
      hepatic microsomal cytochrome P450 activity and hepatocyte proliferation after
      short-term exposure. We previously demonstrated that UG has hepatic tumor
      promoting activity in DEN-initiated female B6C3F1 mice. Thus, we hypothesized
      that MTBE would have hepatic tumor-promoting activity in the same initiation
      promotion model system in which UG was a hepatic tumor promoter. Twelve-day-old
      female B6C3F1 mice were initiated with a single i.p. injection of the mutagen N
      nitrosodiethylamine (DEN) (5 mg DEN/kg, 7.1 ml/kg body weight) or saline.
      Beginning at 8 weeks of age, mice were exposed to 0 ppm or the hepatocarcinogenic
      dose of approximately 8000 ppm MTBE. After subchronic exposure, MTBE
      significantly increased liver weight and hepatic microsomal cytochrome P450
      activity without hepatotoxicity or an increase in non-focal hepatocyte DNA
      synthesis. These are subchronic effects similar to those produced by UG. However,
      MTBE did not significantly increase the mean size of hepatic foci and volume
      fraction of the liver occupied by foci as compared to DEN-initiated controls at
      either 16 or 32 weeks. The lack of tumor-promoting ability of MTBE in DEN
      initiated female mouse liver was unexpected and suggests that MTBE does not
      produce liver tumors through a tumor-promoting mechanism similar to that of UG.

PMID- 9006117
TI  - In vitro formation of DNA adducts by cisplatin, lobaplatin and oxaliplatin in
      calf thymus DNA in solution and in cultured human cells.
AB  - Two interesting representatives of a new generation of platinum-based cytostatic
      drugs that are currently being tested in clinical trials are lobaplatin [1,2
      diaminomethylcyclobutane platinum(II) lactate] and oxaliplatin [1,2
      diaminocyclohexane platinum (II) oxalate]. Since little is known about the DNA
      adduct formation of these compounds, we studied their formation in DNA in vitro
      in calf thymus DNA and in cells. The major adducts formed in vitro were the Pt-GG
      and Pt-AG intrastrand crosslinks. The latter adducts could be detected using a
      recently developed 32P-postlabelling method. Using both this assay and atomic
      absorption spectroscopy, it was shown that there is a substantially higher rate
      of the in vitro adduct formation by cisplatin, compared with lobaplatin and
      oxaliplatin. Platinum concentrations required to obtain 90% cell kill during a 2
      h incubation of A2780 cells were 15 microM for cisplatin and oxaliplatin and 22
      microM for lobaplatin. Using an antiserum originally raised against cisplatin
      treated DNA, we were also able to detect platinum-DNA adducts induced by
      lobaplatin and oxaliplatin. Maximal nuclear staining for all three compounds was
      observed after a 4 h post-incubation period. The nuclear staining level induced
      by cisplatin was about 10-fold higher than after lobaplatin and oxaliplatin
      treatment. GG and AG adducts, measured by 32P-postlabelling, also showed maximum
      levels at about 4 h after treatment. Relative GG peak levels were 4:1:3 for
      cisplatin, lobaplatin and oxaliplatin, respectively. The ratios of GG over AG
      intrastrand crosslinks in the A2780 cells were not significantly different for
      the various compounds. In conclusion, the 32P-postlabelling technique has been
      shown to be appropriate for adduct analysis, not only for the classical Pt
      compounds cisplatin and carboplatin but also for novel platinum compounds like
      lobaplatin and oxaliplatin. Results indicated large differences in reactivity of
      the latter compounds to DNA in vitro, compared with cisplatin. This difference
      was smaller in cells, suggesting enhancement of adduct formation by certain
      cellular mechanisms and/or compounds. From these studies, no conclusions can be
      drawn with respect to the cytotoxicity of the different Pt-GG and Pt-AG
      intrastrand crosslinks formed by these compounds.

PMID- 9006118
TI  - Comparison of transformation by manganese sulfate and 5-azacytidine in Rat 6
      cells overexpressing the c-myc oncogene.
AB  - Rat 6 cells are not transformed by treatment with the well-known carcinogens
      benzo[a]pyrene (BP) or N-methyl-N-nitro-N'-nitrosoguanidine (MNNG). Upon
      retroviral transduction of the mouse c-myc gene, Rat 6 cells showed mildly
      altered morphology and formed microcolonies in soft agar; furthermore, they could
      be transformed by BP and MNNG to form large colonies in agar (Hsiao et al. (1992)
      Mol. Carcinogenesis, 5, 140-154). In the current report, we tested the
      sensitivity of the c-myc-overexpressing cells (Rat 6/c-myc) to two additional
      chemicals: 5-azacytidine and MnSO4. These chemicals differ from the direct-acting
      mutagens tested previously. 5-Azacytidine, a potent DNA methylation inhibitor,
      induced growth of large colonies in soft agar cultures of Rat 6 or Rat 6/c-myc
      cells. On the other hand, MnSO4 only induced transformation in Rat 6/c-myc cells,
      but not the parental Rat 6 cells. Transformants induced by 5-azacytidine lost c
      myc-induced apoptotic cell death, whereas MnSO4-induced transformants showed a
      higher degree of apoptosis than the parental Rat 6/c-myc cells. These results
      suggest that MnSO4 co-operates with overexpressed c-myc in inducing
      transformation, while 5-azacytidine transformation is independent of c-myc
      overexpression and may involve alterations in the regulation of apoptosis.

PMID- 9006119
TI  - Negative interference of metal (II) ions with nucleotide excision repair in human
      cell-free extracts.
AB  - Inhibition of the nucleotide excision repair (NER) process is believed to cause
      the potentiation of the genotoxic and mutagenic effects of DNA damaging agents
      like UV-light or cisplatin by metal ions. However, the precise underlying
      molecular mechanism of this phenomenon is still unknown. Using in vitro assays,
      we have determined the potential interference of several metal (II) ions with the
      lesion recognition and strand incision/displacement steps of the NER mechanism,
      independently from the DNA polymerization step. When combinations of an optimal
      Mg2+ concentration and concentrations of various metal ions in a range from 0.1
      to 1 mM were tested, all combinations, with Mn2+ and Ni2+ excepted, inhibited
      specifically the incision repair activity by human protein extracts. There was a
      good correlation for Cd2+, Co2+, Fe2+, Cu2+, Hg2+, Pb2+ and Zn2+ between an
      inhibiting effect on the incision activity and a reduced protein binding activity
      to a damaged DNA probe as assessed by gel mobility shift assay.

PMID- 9006121
TI  - The subtle work of nursing.

PMID- 9006120
TI  - Identification of genes whose expression is altered during mitosuppression in
      livers of ethinyl estradiol-treated female rats.
AB  - In this study, our goal was to identify genes whose expression in liver is
      altered in female F-344 rats during mitosuppression induced by 42 days of ethinyl
      estradiol (EE) treatment (Yager et al., Carcinogenesis, 15, 2117-2123, 1994).
      Northern analysis demonstrated that the mRNA levels for transforming growth
      factor-beta1 (TGF-beta1) and the mannose 6-phosphate/insulin-like growth factor
      II receptor were significantly increased by EE treatment. Ten cDNA clones
      representing mRNAs whose expression was increased two- to four-fold in the
      mitosuppressed livers were identified by differential display. Sequence analysis
      revealed that one was homologous to the S-24 ribosomal protein and another to
      mitochondrial ATPase subunit e. The remaining clones showed no homology to known
      genes in GenBank. However, the expression of clones 15, 16 and 17 was increased
      in HepG2 cells following treatment with doxorubicin suggesting their induction by
      oxidative DNA damage. These results suggest that two independent but interrelated
      signalling pathways, one mediated through transforming growth factor-beta and the
      other through oxidative DNA damage, may contribute to hepatic mitosuppression
      caused by EE, perhaps through activation of cyclin-dependent kinase inhibitors.

PMID- 9006122
TI  - Direct Access. Alberta nurses: an under used resource?

PMID- 9006123
TI  - Disclosure and reporting of infection with blood-borne pathogens: guidelines for
      registered nurses. Alberta Association of Registered Nurses.

PMID- 9006124
TI  - The benefits of nursing research--putting theory into practice. Interview by M
      Elabdi.

PMID- 9006126
TI  - Burnout among Alberta nurses-a flicker or a forest fire?

PMID- 9006125
TI  - Research education deficits--our solution.

PMID- 9006128
TI  - Laying down the law.

PMID- 9006127
TI  - The fairy godmother syndrome.

PMID- 9006129
TI  - Code for nurses?

PMID- 9006130
TI  - Euthanasia Act to be terminated?

PMID- 9006131
TI  - Education cuts short sighted.

PMID- 9006134
TI  - Making sense of mental state assessment.

PMID- 9006133
TI  - Canaries flutter in continuing madness.

PMID- 9006132
TI  - Wound care challenge: a nursing home case study.

PMID- 9006135
TI  - Sheep.

PMID- 9006137
TI  - Public comment sought on HIV/AIDS.

PMID- 9006136
TI  - A US invasion...?

PMID- 9006139
TI  - Nursing home holiday.

PMID- 9006140
TI  - Handovers in a changing health care climate.

PMID- 9006138
TI  - Reaching out on a bike. Interview by Sam Prenesti.

PMID- 9006141
TI  - Enterprise bargaining and part-time employment.

PMID- 9006142
TI  - Communicators of pain.

PMID- 9006143
TI  - Monitoring glucose in the home.

PMID- 9006144
TI  - What communication skills are most helpful with families grieving a perinatal
      loss? How can I express my concern while providing appropriate care?

PMID- 9006145
TI  - Physiologic assessment of the healthy newborn.
AB  - Care of the stabilized newborn requires an understanding of perinatal (prenatal
      and intrapartum) risk factors, and an accurate, timely assessment in relation to
      these factors. Ongoing assessments during the newborn's hospital stay should be
      based on the data collected during the initial assessment. The newborn should not
      be discharged until concerns are resolved and defined criteria are met. Family
      education is an essential part of newborn care and must include comprehensive
      information in a written as well as verbal format. Documentation must be simple,
      yet allow for inclusion of necessary information. Shortened hospital stays
      challenge neonatal nurses to provide care that allows for quality patient
      outcomes.

PMID- 9006147
TI  - Homeopathy for the holistic nurse: classical vs. contemporary homeopathy.

PMID- 9006146
TI  - AHNA holistic nurse of the year. Interview by Judy Koenig.

PMID- 9006148
TI  - Nursing and spirituality: one nurse's account.

PMID- 9006150
TI  - Holistic nursing ... everything old is new again.

PMID- 9006149
TI  - Exploring health care in the southwest: the Navajo perspective.

PMID- 9006151
TI  - Being on the other side.

PMID- 9006152
TI  - The holistic nurse entrepreneur: dreams and visions.

PMID- 9006153
TI  - Transylvania: the ball-point pen connection.

PMID- 9006154
TI  - Transitional arrangements for specialist nurses.

PMID- 9006155
TI  - BJN survey reveals that 30% of nurses take on extra work to pay the bills.

PMID- 9006156
TI  - Postoperative nausea and vomiting. 1: Physiology and aetiology.
AB  - There is a vast amount of research available relating to postoperative nausea and
      vomiting (PONV). This research has been analyzed and summarized in a series of
      two articles which draw out the main factors influencing the incidence and
      affecting the treatment of the condition. This, the first article, will describe
      the physiological processes that result in PONV. An analysis will then follow of
      the many factors that contribute to the complex multifactorial aetiology of PONV.
      These factors include personal, preoperative, intraoperative and postoperative
      variables which affect differing neurotransmitter centres in the chemoreceptor
      trigger zone (CTZ) which is situated in the brainstem. These variables will then
      be related to the appropriate neurotransmitter centre allowing a greater
      understanding of the most likely physiological pathways involved in specific
      cases of PONV. The second article will explore the management and treatment of
      PONV.

PMID- 9006157
TI  - Alternatives to seclusion in psychiatric care.
AB  - The use of seclusion in psychiatry is declining. Its punitive nature has been
      acknowledged and alternative, more therapeutic approaches are needed to deal with
      disturbed patients. What alternatives are available? This article reports a study
      that sought to examine the response to incidents that formerly would have led to
      seclusion in one psychiatric intensive care unit. The sample consisted of 50
      incidents. Information on the incident and subsequent action was recorded on
      standard incident forms and specially designed data collection sheets. The most
      frequent type of incident was damage to property, followed by direct or
      threatened physical assault on staff. The most common response was one-to-one
      nursing support, followed by the use of medication. In just over half the
      incidents, both responses were used together. This therapeutic strategy
      demonstrates that aggressive incidents can be dealt with safely without recourse
      to seclusion.

PMID- 9006159
TI  - The scope of professional practice in specialist practice.
AB  - The Scope of Professional Practice (UKCC, 1994a) now offers nurses, midwives and
      health visitors new opportunities to develop their clinical role. Role expansion
      is at the centre of debate in the health service. In the spirit of Scope, trusts
      and regional health authorities have been experimenting with new roles that
      combine medical and nursing practice in order to promote a holistic approach to
      health care. Education, experience and the appropriate clinical competency are
      the foundations for role expansion and the development of professional practice.
      However, some of the new roles and innovative practices have also been targeted
      at reducing junior doctors' hours (Read and Graves, 1994). New roles must be
      evaluated before they are allowed to develop and there is an urgent need for
      national evaluation of the initiatives underpinning Scope. This article examines
      the changing role of practitioners in specialist practice. The ethical,
      professional and legal issues surrounding these changes will also be considered.

PMID- 9006158
TI  - Attitudes of practitioners to lesbian, gay and bisexual clients.
AB  - Many health-care workers have a negative attitude towards their lesbian, gay and
      bisexual clients. Negative attitudes regarding same-sex attractions appear to be
      deeply ingrained in the majority of nurses' minds as a result of the
      socialization process. It is vital that nursing embraces issues related to sexual
      orientation so that quality health care can be provided for all. Doctors also
      have a responsibility to address the issue of homophobia both within their
      profession and in relation to their clients. To facilitate this, a framework
      using a sexual health model should be employed as this would encourage the
      clinician to contemplate these sensitive issues. This article will explore the
      attitudes of nurses and will outline the implications for care and education.

PMID- 9006160
TI  - Economics of evidence about nurse specialization.
AB  - If nurse specialization is to flourish within the expected financial constraints
      then advocates will have to focus attention on research-based evidence about
      clinical practice that is relevant to clients. This article examines the kinds of
      evidence that might be sought and considered before decisions are made about the
      allocation of scarce resources to nursing services. It is suggested that reasoned
      decision making for health services in that context would require convincing
      evidence that each particular commitment of resources to nursing can be expected
      to contribute as a set of inputs towards the best possible achievement of overall
      objectives for health services within the anticipated constraints on resources
      available. If so, it would be reasonable to expect that those with resources to
      allocate will seek and will consider evidence about costs associated with
      nursing, including adverse risks, as well as that about relevant benefits from
      nursing. Advocates for nursing, or for specialisms among nurses, would then do
      well to demonstrate that they take evidence about both benefits and costs
      seriously when presenting their case, rather than dismiss either as being merely
      an annoying and unreasonable distraction.

PMID- 9006161
TI  - Writing an academic essay: a practical guide for nurses.
AB  - Writing academic essays can be a major hurdle and source of anxiety for many
      students. Fears and misconceptions relating to this kind of writing can be
      dispelled if the task is approached in a logical and systematic manner. This
      article outlines the key steps involved in successfully completing an essay and
      provides some practical tips to facilitate critical and analytical writing. These
      steps are: analysing the task; exploring the subject; planning the essay; writing
      the account; and revising the drafts. Although this process is challenging,
      academic writing is a means of developing both personally and professionally.

PMID- 9006162
TI  - Stress in nursing and patients' satisfaction with health care.
AB  - The aim of this study was to investigate the factors that contribute to the
      stress reported by nurses and patients. Thirty-four nurses in a London teaching
      hospital completed the nurse stress index and the Spielberger state trait anxiety
      inventory, and attitudes towards the ward and nursing care were measured in 52
      patients. Nurses in the sample reported significantly greater problems than the
      norm in dealing with stress (as measured by the nurse stress index). In
      particular, they expressed difficulty in dealing with patients and their
      relatives, with conflict between home and work, and with and pressure resulting
      from problems concerning confidence and competence in the role. Patients were
      generally satisfied with the health care they received. There was a positive
      relationship between the time that patients spent talking to nurses and the
      degree to which nurses were perceived as helpful. Results are discussed in terms
      of possibilities for further research and implications for the design of future
      intervention programmes aimed at reducing job-related stress in hospitals.

PMID- 9006163
TI  - Irriclens: a sterile wound cleanser in an aerosol can.
AB  - Irriclens (ConvaTec) is the first wound cleanser to be presented in an aerosol
      can. Wound cleansing has become a ritualistic task; however, it should only be
      carried out if specifically required. Antiseptics have traditionally been used
      for wound cleansing, but in many areas are now being replaced by normal saline.
      Irriclens is a sterile, aqueous 0.9% sodium chloride solution, which can be used
      to cleanse a wound or for irrigation. Irriclens has the potential to be cost
      effective as it prevents wastage and reduces the need for supplementary
      equipment.

PMID- 9006165
TI  - A new professional practice model for nursing.

PMID- 9006164
TI  - Continuous quality improvement in pressure sore prevention.
AB  - The final article in this series examining the draft national clinical guidelines
      for pressure sore prevention and management considers continuous quality
      improvement. Different professions use different terminologies to describe
      quality assurance: nurses link it to 'standard setting' whereas the medical
      profession uses the term 'medical audit'. This article discusses the concepts of
      quality and audit in relation to pressure sores and their prevention. In
      particular, it addresses the importance of scientific rigour and
      multidisciplinary team working and management involvement.

PMID- 9006166
TI  - Nurse shortages: why are nurses leaving the NHS?

PMID- 9006167
TI  - Sudden infant death: who's to blame?

PMID- 9006169
TI  - Psychology. 5: Implications of the ageing process for nursing practice.
AB  - Many people are living longer and, as a consequence, the UK is populated by
      increasing numbers of elderly people. This trend towards an increase in longevity
      has been matched with an increase in morbidity, despite contemporary professional
      and lay interest in the adoption of healthier lifestyles. Hence, expertise in
      elderly care is likely to continue to be important for many health-care
      professionals. This article considers aspects of the ageing process and draws
      attention to the psychological interpretations of personality and life span,
      social isolation, intelligence and memory related to elderly people. The main
      conclusions drawn are that, although becoming older can be associated with health
      care problems, the process of ageing is individually experienced and it is
      inappropriate to assume that all elderly people share common needs. A number of
      implications for nursing practice are highlighted and recommendations to enhance
      care are made.

PMID- 9006168
TI  - Homeostasis: restoring the internal wellbeing in patients/clients.
AB  - This article gives a historical perspective of homeostasis and explores the
      concepts surrounding the term. The importance of the internal environment and the
      dynamic nature of homeostasis are discussed. Issues of homeostatic control and
      maintenance are highlighted and the role of feedback mechanisms is clarified. A
      rationale is presented to support the argument that the objective of holistic
      nursing care is to restore physical and emotional homeostasis, i.e. to facilitate
      the restoration of the internal wellbeing in our clients/patients. Two aspects of
      a non-homeostatic model of health, namely the mind-body dualism and the
      reductionist approach, are considered.

PMID- 9006170
TI  - Prepacked take-home analgesia for day case surgery.
AB  - Postoperative pain is one of the main barriers to increasing the range of
      procedures suitable for day case surgery. Effective strategies for treating
      postoperative pain must be developed and tested if this range is to be extended.
      This article examines the effectiveness of prepacked take-home analgesia in
      providing pain relief for patients following day case surgery. The composition of
      the analgesia pack was varied according to the type of operation undertaken.

PMID- 9006171
TI  - Child prostitution: reaching out to children who sell sex to survive.
AB  - Childhood prostitution is an area that most health-care workers do not come into
      direct contact with other than through media coverage. It is difficult to obtain
      a national picture of the scale of the problems associated with childhood
      prostitution as research has been sparse, fragmented and mainly localized Health
      and social care professionals need to be aware of the factors that influence
      routes into prostitution such as childhood abuse, poverty and breakdowns in
      family relationships if they are to provide relevant and appropriate health
      promotion interventions. This article explores the social economical and
      political issues surrounding childhood prostitution, and highlights come
      interesting initiatives which have been implemented by health and social care
      professionals.

PMID- 9006172
TI  - Neonatal intensive care nurse stressors: an American study.
AB  - The purpose of this study was to determine the frequency of selected stressors
      and the level of associated stress experienced by neonatal intensive care unit
      (NICU) nurses in the USA, and to identify their responses/coping mechanisms. The
      research instrument consisted of demographic data (education, location of
      practice, age, years in practice, gender) and a modification of the Stress Audit
      tool developed by Popoff and Funkhouser (1975). Participants were randomly chosen
      from health-care units located in the upper Midwest of the USA. Fifty-nine nurses
      (35%) responded to the postal survey. In terms of scale items, floating out of
      the unit (ability to staff other units when necessary) was the most stressful
      item and routine procedures the least stressful item. From a subscale
      perspective, knowledge was the least stressful and management the most. Subscale
      scores did not differ by marital status, number of years of practice as a
      registered nurse, or years of practice in NICU. Coping with stress was best
      facilitated by discussion with coworkers. Consistency of care, inservice
      education, mental health days (time off for stress relief, paid or unpaid) and
      staff support groups were reported as helpful in coping with job-related stress.

PMID- 9006173
TI  - Steripaste: a new zinc bandage that is preservative free.
AB  - Chronic leg ulcers often present as a chronic open wound with surrounding
      eczematous skin. Paste bandages are widely used to treat such ulcers and their
      associated skin conditions, but can often lead to hypersensitivity reactions
      leading to contact dermatitis. This product focus features Steripaste (Seton
      Healthcare) which is a new preservative-free, medicated paste bandage that is
      available on the Drug Tariff for use in the community sector.

PMID- 9006174
TI  - Should there be a nursing presence in the operating theatre?
AB  - Theatre nurses currently face the greatest threat to their existence since the
      evolution of the theatre nursing role. Traditionally perceived as task-oriented
      and separatist, the nature of the current theatre nursing role has led to the
      operating department being devalued as a clinical placement for preregistration
      student nurses which has a consequent effect on recruitment and retention
      problems. This article examines what the nurse provides, or could provide, in the
      operating theatre. The themes are that theatre nurses must give due consideration
      to the short-term future of their clinical role in order to regain status in the
      hierarchy of mainstream nursing.

PMID- 9006175
TI  - Pressure sore management in the independent sector: 1.
AB  - Little is known about pressure sore prevention and treatment in the independent
      sector. With a rapidly increasing number of care settings taking over
      responsibility for continuing care, particularly for elderly people, it is
      important that essential nursing care is provided at nationally agreed standards.
      This is the first of two articles which explore current practice in the
      independent sector of a large northern city. Background information on the study,
      details of data collection and analysis and baseline data on current practice are
      presented. This study investigates the extent of evidence-based practice,
      equipment use, educational needs, patient and informal carer involvement and
      maintenance of quality of care. Initial conclusions indicate that pressure sore
      management in the independent sector is evidence-based. However, in many areas of
      practice, personal observations and experience continue to take precedence over
      research evidence.

PMID- 9006176
TI  - The value of the generalist nursing domain.

PMID- 9006178
TI  - Residential care for people with learning disabilities.

PMID- 9006177
TI  - Specialist and advanced nurses need representation.

PMID- 9006180
TI  - Psychology. 6: What's your problem? A consideration of problem solving.
AB  - A substantial component of nursing is concerned with solving problems, or helping
      patients and clients to solve problems for themselves. This article considers
      problem solving in a range of nursing practice settings and outlines how
      psychology can help to explain and inform this process. The diverse nature of
      problems which nurses might encounter in their work are discussed and
      recommendations for the application of problem-solving strategies are offered. No
      single approach to problem solving is sufficiently flexible to address the
      complex challenges met in nursing practice, and hence an eclectic approach to
      problem solving is proposed.

PMID- 9006179
TI  - A study of postoperative wound management in nursing.
AB  - Wound management has changed considerably over the past decade. The change from
      dry to moist healing is the result of new scientific evidence. The number and
      variety of wound care products available on the market have increased, along with
      the importance of the acceptability of a particular type of product to individual
      patients' lifestyles. Annual worldwide expenditure on wound care is estimated to
      be in the region of $7 billion (US). The implications of efficient and effective
      wound healing for both the patient and the economy, therefore, are massive. This
      article presents the results of a study of postoperative wound management. The
      need for consistent and regular wound assessment is demonstrated and linked with
      length of hospital stay.

PMID- 9006181
TI  - The psychosocial effects of skin diseases: need for support groups.
AB  - Patients with psoriasis may be psychologically vulnerable and suffer social
      isolation as a result of physical disfigurement. It is important that nurses are
      able to assess the psychological needs of patients and, where necessary,
      facilitate the development of positive coping strategies. Staff and patients in
      the dermatology department at the Queen's Medical Centre, Nottingham, set up a
      support group to try to address these issues. One year on, an evaluation of the
      efficacy of the group has shown that such gatherings are essential to the
      psychological wellbeing of individuals with skin complaints.

PMID- 9006182
TI  - Health of the Nation for people with learning disabilities.
AB  - This article explores issues related to the health of people with learning
      disabilities, with particular reference to the Department of Health (1995a)
      document The Health of the Nation: A Strategy for People with Learning
      Disabilities. This publication has stimulated care staff across all agencies to
      take a fresh look at this client group and their health needs in the five key
      areas: coronary heart disease and stroke; cancers; HIV/AIDS and sexual health;
      accidents; and mental health.

PMID- 9006183
TI  - Challenging behaviour in children with learning disabilities.
AB  - This article outlines the initial stages of an ongoing experiment to evaluate the
      comparative efficacy of two different therapeutic interventions--behaviour
      modification and gentle teaching--in the management of challenging behaviour in
      children who have learning disabilities. Using a workshop approach, parents are
      taught the principles and practice of one of these two interventions to enable
      better management of their child's challenging behaviour. A range of intervention
      outcomes are then compared with those of a control group. Preliminary analysis of
      data has been conducted on information gathered from those parents (n = 24) who
      attended the gentle teaching workshop only. The results indicate that brief
      intervention training in gentle teaching can have a positive impact upon the
      challenging behaviour of the child.

PMID- 9006184
TI  - Does nicotine have beneficial effects in the treatment of certain diseases?
AB  - Although tobacco smoking has long been associated with diseases of the lungs and
      cardiovascular system, numerous studies have demonstrated a negative association
      between tobacco smoking and ulcerative colitis, and the neurodegenerative
      diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). The evidence
      suggests that nicotine--the main pharmacologically active ingredient of tobacco-
      appears to be responsible for this effect. Pure nicotine has no known
      carcinogenic properties and can be administered in numerous ways including
      transdermal patches and tablets. As a therapeutic agent, its association with
      tobacco can be likened to morphine and opium smoking. There is ample clinical
      evidence to suggest that nicotine could be beneficial in the treatment of some
      patients with diseases. Pharmacologically, nicotine acts on cholinergic
      (nicotinic-specific) receptors which are depleted in AD and PD. Nicotinic
      receptors also interact closely with several neurotransmitters including
      dopamine, which is implicated in both PD and Gilles de la Tourettes's syndrome.
      There is no doubt that tobacco smoking can be harmful and no-one should be
      encouraged to smoke. However, although nicotine has many harmful side-effects, it
      may have therapeutic value or at the very least be a useful tool for future drug
      development.

PMID- 9006185
TI  - The elective experience: student choice in nurse education.
AB  - This article highlights the importance of choice in nurse education. It is
      suggested that for too long nurse education has ignored specialties such as
      forensic or child and adolescent mental health, and points to the elective
      placement as an invaluable, rich and rewarding learning experience. Through a
      process of negotiation involving the learner, the tutor and clinical staff,
      student nurses are empowered to take responsibility for their education and make
      choices for themselves. The elective placement is a time to consolidate
      knowledge, develop practice and reflect personal agendas within the nursing
      curriculum. Since nursing requires practitioners to be able to make decisions,
      solve problems and act autonomously, choice in education is crucial. This is in
      keeping with what nursing strives for, i.e. empowering others to take
      responsibility and make choices for themselves.

PMID- 9006186
TI  - Effects of the purchaser/provider split on research implementation.
AB  - The issues surrounding the use of research to inform practice and the potential
      problems involved in this process have been the subject of debate within nursing
      for many years. The purchaser/provider relationship has led to an increase in the
      number of challenges nursing encounters regarding the implementation of research.
      These challenges and relationships, which will either promote or prevent the
      implementation of research in nursing practice, are explored using Nolan and
      Grant's (1993) framework. The analysis concludes that implementation of nursing
      research needs to be part of the contracting process involving shared dialogue
      between purchasers and providers. Discussions on clinical effectiveness need to
      include nursing evidence as part of the health-care contracting process.
      Professionals involved in contracting require equal knowledge about research and
      joint professional values in order to support its implementation within
      contracting appropriately.

PMID- 9006188
TI  - Reforms round-up. Beware managed care.

PMID- 9006187
TI  - UKCC launches professional conduct complaints report.

PMID- 9006189
TI  - Offering choices or containing costs?

PMID- 9006190
TI  - Managing contracts.

PMID- 9006191
TI  - Aging patients, aging nurses.

PMID- 9006193
TI  - Nurses' needs ignored.

PMID- 9006194
TI  - Patient safety under threat.

PMID- 9006192
TI  - The state of mental health.

PMID- 9006195
TI  - Nightmare on night shift.

PMID- 9006196
TI  - Care comes before profit.

PMID- 9006197
TI  - Depression: moving on.
AB  - Care for patients who are (or may be) depressed is delivered in a range of
      practice settings. All nurses, midwives and health visitors, therefore, need to
      be alert to the signs of depression, in order that appropriate action can be
      taken--whether this is initiating self-help, using practical interventions or
      referring on, where necessary. This Learning Unit focuses particularly on the
      assessment and prevention of depression and is relevant whatever the setting in
      which you work.

PMID- 9006198
TI  - Food in the balance: the nurse's role.
AB  - Good nutrition is fundamental to health and wellbeing, and nurses in all settings
      have an important role to play in this area of health promotion. In meeting this
      challenge nurses need a sound knowledge of nutrition, a recognition of the
      diverse factors which influence what people consume, and practical know-how about
      ways in which health dietary choices can be made easier for patients and clients.

PMID- 9006199
TI  - Health Insurance Portability: new law protects nurses who change jobs.

PMID- 9006200
TI  - Peptic ulcer disease (continuing education credit).

PMID- 9006201
TI  - The Americans with Disabilities Act.

PMID- 9006202
TI  - Laying off senior RNs: when is it age discrimination?

PMID- 9006204
TI  - What is the role of the RN in administering conscious sedation?

PMID- 9006203
TI  - Ohio Board of Nursing. Responding to nurses' questions.

PMID- 9006206
TI  - Pointers for nurses entering oncology.

PMID- 9006207
TI  - Surviving Hurricane Fran and remembering lessons for daily living.

PMID- 9006208
TI  - Understanding the latest news on gene discoveries.

PMID- 9006205
TI  - Thomas and other World Wide sites can help nurses access on-line legislative
      information.

PMID- 9006209
TI  - Examining the path of healthcare reform: where does it lead?

PMID- 9006210
TI  - Whose needs does the computer serve?

PMID- 9006211
TI  - Nurses reach out to Internet.

PMID- 9006212
TI  - Do antibiotics decrease effectiveness of oral contraceptives?

PMID- 9006213
TI  - Criteria for computer systems that support the nursing process.

PMID- 9006214
TI  - Nursing education responds to changes.

PMID- 9006215
TI  - Latex allergy: protect yourself and your patients.

PMID- 9006216
TI  - Rader offers creative dementia care ideas.

PMID- 9006217
TI  - Assessment of blood glucose self-monitoring skills in a camp for diabetic
      children: the effects of individualized feedback counselling.
AB  - We report a study of the accuracy and precision of blood glucose self-monitoring
      by children and adolescents attending a diabetic summer camp, and of the efficacy
      of feed-back counselling aimed at correcting identified problems. Of 96 eligible
      campers, 71 were enrolled. Of those, 41 were found to test with random error >
      20% or systemic error > 10% and were randomized into control (n = 19) and
      intervention (n = 20) groups. Intervention consisted of one or two 15- to 30-min
      individualized sessions that involved testing under supervision, corrections of
      errors, and discussion of the importance of correct testing. Group sessions were
      also given on the same aspects. Re-testing at the end of camp revealed only
      marginal changes in the results for either group. Evaluation during counselling
      indicated that most problems were not due to lack of knowledge of the skills
      involved. We concluded that poor blood glucose monitoring by children and
      adolescents results most frequently from poor attitude rather than lack of skill.

PMID- 9006218
TI  - Factors influencing the attitudes held by women with type II diabetes: a
      qualitative study.
AB  - Results of formal diabetes education are still considered unsatisfactory but
      could be improved by being more patient centred. The purpose of this study was to
      investigate attitudes of people with diabetes toward their disease and its
      treatment from their point of view and the research question answered was, 'What
      are the feelings and beliefs of people with NIDDM about diabetes and its
      treatment?' Data were collected through in-depth interviews using the general
      interview guide approach. Seven interviews with adult type II diabetes from rural
      Illinois were tape recorded and transcribed. The naturalistic content analysis
      revealed four categories: physician's reaction at diagnosis; perceived
      seriousness of diabetes; physician-patient relationship; and self-care. A finding
      that was not described in any literature reviewed by the researcher was that the
      reaction and attitude physicians displayed toward patients at the point of
      diagnosis were crucial in influencing attitudes toward perceived seriousness of
      the disease and consequently compliance. Newly diagnosed patients showed strong
      motivation with regard to treatment. However, difficulties in adhering to a
      treatment plan and inadequate perceived seriousness of the disease were factors
      contributing to a lack of compliance. Participants reported that when diabetes
      complications started their compliance improved.

PMID- 9006219
TI  - The cognitive orientation of compliance in short- and long-term type 2 diabetic
      patients.
AB  - Previous research showed that providing diabetic patients with information about
      diabetes is mostly insufficient for compliance. The purpose was to develop a new
      model for studying and promoting compliance in diabetes based on the theory of
      cognitive orientation (Kreitler & Kreitler), which assumes that in addition to
      knowledge it is necessary to consider the patient's goals, values and self image.
      We expected cognitive contents (beliefs) to be related to compliance, more in
      long-term than short-term patients. The subjects were 112 Type 2 diabetic
      patients. They were administered a Cognitive Orientation Questionnaire of
      Diabetic Compliance assessing cognitive contents in terms of four belief types
      (goals, norms, self and general) referring to relevant themes (e.g. discipline,
      reducing tensions). Compliance was assessed in terms of physical measures (HbA
      and number of complications) and behavioral measures based on information
      provided by the medical staff about glucose testing, taking medication, diet,
      exercise, independence, and follow-ups. The results showed that beliefs predicted
      (by discriminant analyses) the compliance measures more in long-terms and enabled
      describing the personality dynamics of compliers. The findings support a
      cognitive model of compliance. It predicts better in long-term than short-term
      diabetic patients.

PMID- 9006220
TI  - Measuring diabetes-related attitudes: the use of a USA-developed instrument with
      Australian nurses.
AB  - The revised Diabetes Attitudes Scale (DAS) was completed by nearly 1000 nurses
      and nursing students in South Australia. Confirmatory factor analysis was used to
      compare the factor structure with that previously obtained in the USA with
      patients with diabetes. The instrument was found to be robust. It was concluded
      that only one item of the 50-item scale is unsuitable for inclusion in studies
      which aim to compare patient and health professional attitudes.

PMID- 9006221
TI  - Patient-physician interactions in diabetes management: consistencies and
      variation in the structure and content of two consultations.
AB  - The structure and content of medical consultations concerning diabetes were
      examined in two, successive quarterly medical consultations between two
      physicians and their diabetes patients (N = 44). The consultations were audio
      taped and coded for structure (e.g. question asking, information giving) using a
      modified version of the Roter Interactional Analysis System (inter-coder
      correlations typically exceeded 0.90 for the composite variables derived from the
      coding system). The tapes were also coded for content by monitoring the topics
      discussed (e.g. diet, medication, exercise). The majority of the interactions
      consisted primarily of information giving and positive talk on the part of both
      patients and providers. Nutrition-related issued, blood glucose monitoring,
      medication and exercise were addressed in the majority of interactions, but other
      regimen areas such as foot care, smoking habits, and alcohol were seldom
      discussed. There was little stability across the two consultations in terms of
      either structure (median test-retest correlation = 0.24) or content (majority of
      test-retest correlations were below 0.30). The importance of studying more than
      one patient-physician encounter when studying interaction style and content is
      discussed, as is the need for investigation of interactions between non-physician
      health care providers and patients with chronic disease.

PMID- 9006222
TI  - Diabetes teaching--outcome analysis.
AB  - A comprehensive database has been maintained on patients attending the St. Paul's
      Hospital Diabetes Teaching and Treatment Centre (DTTC) since 1984. In November
      1995, four sets of patients, all of whom had returned to the Centre, were
      identified for an outcome study. The sets were: insulin-dependent diabetes
      mellitus (IDDM), diet-treated non-insulin-dependent diabetes mellitus (NIDDM),
      oral agent-treated NIDDM, insulin-treated NIDDM. Data on glycosylated hemoglobin
      (A1c) values, percent ideal body weight (%IBW), home blood glucose monitoring
      (HBGM/week were analysed for all sets; data on hypoglycemic events/month were
      analysed only for the group with IDDM. Results demonstrated that patients in all
      groups performed significantly more HBGM over time. Downward change in %IBW in
      the diet-treated and oral agent groups was significant. Upward change in %IBW was
      significant in the IDDM group. Hypoglycemic events did not significantly increase
      in IDDM patients even though A1c improved. Most notably, the A1c values improved
      in all four groups up to 8 years after the first DTTC visit. Implications for
      practice are suggested.

PMID- 9006223
TI  - Professional responses to innovation in clinical method: diabetes care and
      negotiating skills.
AB  - OBJECTIVE: To describe the responses of family doctors and nurses to applying an
      innovative clinical technique and technology in the context of a randomised
      controlled trial. DESIGN: Multi-faceted descriptive analysis of professional
      responses in the experimental arm of the trial. SUBJECTS AND SETTING: 29 family
      practices involving 30 doctors and 33 nurses over a 3-year time scale and 200
      patients with type II diabetes. INTERVENTION: A new visual agenda-setting
      technology and other visual aids applied using the techniques of negotiation and
      motivational interviewing. OUTCOME MEASURES: Uptake of training, use of the
      method, group discussions, willingness to accept consultation recordings.
      RESULTS: 100% of clinicians welcomed two or more formal training sessions. The
      agenda-setting technology was used frequently by 71% of clinicians and
      occasionally by a further 22%. High levels of engagement with the method occurred
      among nurses but many doctors also reported benefits. CONCLUSIONS: Family doctors
      and nurses in Wales have found a new technology to facilitate negotiation in
      diabetes consultation acceptable and useful. Analysis of outcome is now awaited.

PMID- 9006224
TI  - Developing a training programme in patient-centred consulting for evaluation in a
      randomised controlled trial; diabetes care from diagnosis in British primary
      care.
AB  - AIM: To develop a feasible/theoretically based training programme in patient
      centred consulting, for evaluation in a randomised controlled trial of diabetes
      care from diagnosis. METHODS: The programme was developed with four primary care
      teams and their patients in an action research framework, with observation of
      diabetes review consultations before and after training, and evaluated by
      questionnaire after each training session, among 23 general practitioners and 32
      practice nurses from 21 practices in the trial. RESULTS: The observation study
      identified opportunities and obstacles to introducing a patient-centred approach
      into daily practice, especially in relation to time management and skill needs.
      The modified training programme was rated highly by participating general
      practitioners and nurses. CONCLUSIONS: Developing training programmes with the
      help of participating primary care teams ensures relevance and feasibility.
      Patient-centred consulting demands a shift from habitual consulting patterns.
      Practitioners are implementing the approach in practice, and the impact on
      patients is now under evaluation in the randomised controlled trial.

PMID- 9006225
TI  - Diabetes education in the elderly: a 5-year follow-up of an interactive approach.
AB  - A continuing interactive educational model was established for elderly patients
      with diabetes mellitus. The effects were studied in 148 diabetic patients aged >
      or = 60 years who participated in 60 monthly scheduled interactive meetings over
      a 5-year period. The meetings were performed as group discussions, cultural
      activities, dining out, and the like. Empowering patients with skills,
      perceptions and feelings to cope with diabetes and metabolic control was
      emphasized, rather than clinical aspects. Comparison between pre-programme and 5
      years later demonstrates a significant increase (P, 0.001) of knowledge and
      skills to deal with treatment requirements, and a reduction in body weight and
      antidiabetic medication (daily doses of insulin and oral compounds; P < 0.01 and
      P < 0.05, respectively). HbA1c levels improved significantly (P < 0.02). There
      were less diabetes related conditions requiring emergency services and hospital
      admission.

PMID- 9006226
TI  - Knowledge and diabetes self-management.
AB  - This paper discusses the role of knowledge in the self-management of diabetes
      mellitus and addresses limitations in the measurement of knowledge in studies
      which have been undertaken. In addition, the findings of a recent investigation
      related to knowledge of diabetes in young adults with the condition are reported.
      The results showed high levels of knowledge and glycosylated haemoglobin values
      which were acceptable when length of time with diabetes was considered. However,
      no relationship between knowledge and level of glycaemic control was
      demonstrated. In the light of recent research confirming the need for tighter
      metabolic control, the implications of these findings in relation to future
      research and the education of health care professionals are considered. Although
      this paper related to diabetes mellitus many of the issues raised are equally
      applicable to the wider forum of chronic illness management.

PMID- 9006227
TI  - Patient psychological and information needs when the diagnosis is diabetes.
AB  - People receiving a diabetes diagnosis must absorb information, change habits and
      adopt new behaviours almost immediately. Guidelines thoroughly cover the medical
      aspects of initial management however the information and psychological needs of
      patients are not addressed. This study aimed to identify diabetes patient needs
      for information and emotional support at the time of diagnosis. A sample of 1159
      patients completed a questionnaire which assessed their concerns and information
      preferences at the time of diagnosis (response rate 64.4%). A sample of 100
      general practitioners (GPs) were interviewed about their perceptions of these
      issues using a subset of items from the patient questionnaire. The diagnosis of
      diabetes was distressing for 60% of responders and 23% wanted more emotional
      support. Immediate issues such as injections were major concerns for patients and
      GPs correctly identified these. However GPs significantly overestimated
      complications as a concern for patients at diagnosis. Patients preferred diabetes
      educators and courses as sources of information. Satisfaction with information at
      diagnosis was high (80%), however younger patients were dissatisfied with their
      discussions concerning diabetes therapy. The findings suggest that clinicians
      giving a diagnosis of diabetes should: (1) be aware of patient variability in
      needs for emotional support and information preferences, (2) ask patients for
      their preferences and offer choices if available and (3) provide more information
      about treatment and increase patient involvement in discussions about therapy.

PMID- 9006228
TI  - Hypoglycaemia induces emotional disruption.
AB  - This study investigated how hypoglycaemia affects mood, whether psychological
      characteristics mediate an emotional disturbance during hypoglycaemia. Ten IDDM
      patients (1 female) were studied, aged [mean (range)] 28 (20-37) years, body mass
      index (BMI) 23.4 (19.6-25.7) kg/m2, diabetes duration 11 (7-15) years, HbA1c 7.5
      (6.0-8.7)%. Patients underwent a standardized stepwise, hypoglycaemic,
      hyperinsulinaemic clamp, performed in steps of 0.5 mmol/l from 4.0 mmol/l to a
      glucose nadir of 2.0 mmol/l. At euglycaemia, the Symptom Checklist-90 (SCL-90)
      was administered. The Profile of Mood States (POMS) was completed at 4.0 and 2.5
      mmol/l, while the feelings chart of the COOP/WONCA was filled out at euglycaemia
      and all hypoglycaemic steps. RESULTS: The t-test for the POMS demonstrated a
      significant increase for anger (P < 0.05). COOP/WONCA scores displayed a
      progressive negative change in mood for each hypoglycaemic step, albeit with a
      large interindividual variability. Hostility (SCL-90) significantly interacted
      with anger (POMS) at 2.5 mmol/l (P < 0.05). CONCLUSIONS: Progression of
      hypoglycaemia negatively alters the overall mood state. IDDM patients
      characterised by high scores on hostility (SCL-90) apparently are more prone to
      experience an increase in anger (POMS) during hypoglycaemia.

PMID- 9006229
TI  - Structured treatment and teaching programme for type 2 diabetic patients on
      conventional insulin treatment: evaluation of reimbursement policy.
AB  - The aim of the study was to evaluate the practicability and efficacy of a
      structured treatment and teaching programme (STTP) for type 2 diabetic
      outpatients on conventional insulin treatment after introducing remuneration for
      physicians. Reimbursement policy for the STTP was introduced in the state of
      Brandenburg, Germany, in July 1993. Between August 1993 and February 1994, 108
      physicians and their assistants participated in a postgraduate seminar, which is
      a prerequisite for remuneration. A standardised interview was performed with 103
      physicians and their paramedical personnel. Twenty of the practices who had
      performed STTP were visited in order to collect data on all the patients who had
      participated in the programme up to September, 1994. Within the first year
      already 10% of the target group of physicians participated in the seminars. The
      seminar and the programme were very well accepted. An improvement of HbA1c levels
      was observed in patients who had started insulin treatment (n = 35: 9.7 +/- 1.6%
      of total Hb before, 8.2 +/- 1.3% of total Hb after the programme) and in those
      who were already being treated with insulin before the STTP (n = 125: 9.6 +/-
      2.5% of total Hb before, 8.1 +/- 1.4% of total Hb after the programme). The
      results of the study demonstrate the efficacy and practicability of an STTP for
      type 2 diabetic patients on conventional insulin therapy in ambulatory health
      care.

PMID- 9006230
TI  - Communication problems on an oncology ward.
AB  - Within the field of oncology, the communication of an unfavourable diagnosis is
      regarded as a stressful event that affects all members of the oncology team, as
      well as the patient. In this exploratory study we found that the communication
      problems between doctors, patients and nursing staff were related to insufficient
      information exchange. A psychosocial registration sheet was developed in order to
      improve communication on the ward. The effects of the new approach are briefly
      commented upon.

PMID- 9006231
TI  - Patients' perceptions on informed consent and the quality of information
      disclosure in clinical trials.
AB  - In a survey on 26 clinical trials we studied how patients experience and evaluate
      the information disclosure on the clinical trial they are enrolled in and which
      factors influence patients' perceptions of information disclosure. Our objective
      was to obtain more insight thereby in how informed consent is applied in the
      daily practice of clinical trials. Interviews were held with 198 adult patients
      and 32 trial-clinicians. Instead of focusing on patient comprehension of the
      information disclosed we analyzed patient perceptions of informed consent.
      Patients proved to be quite satisfied with the oral and written information
      disclosure. Patients' perceptions of the manner and content of information
      disclosure are influenced by more general attitudes towards medical care,
      research and institutions. Patients' trust in medical experiments, belief in the
      integrity of physicians and interest in medical affairs have an impact on the way
      patients perceive information disclosure. To improve the quality of the informed
      consent procedure, we propose a patient motivation classification (PMC) to enable
      trial-clinicians to gain more insight into patient motivation. Relevant factors
      found in our data have been used as criteria for classification. An informed
      decision making checklist (IDC) is suggested for patients as a general outline
      for patient education, covering relevant socio-psychological factors of
      enrollment.

PMID- 9006233
TI  - Meta-analysis of the effects of psychoeducational care in adults with chronic
      obstructive pulmonary disease.
AB  - Meta-analysis, a quantitative research review, was conducted on 65 studies of the
      effect of education, exercise and/or psychosocial support (hereafter called
      psychoeducational care) in adults with chronic obstructive pulmonary disease
      (COPD). Studies ranged in publication date from 1954 to 1994. Only 34% of studies
      had subjects that were randomly assigned to treatment condition, and only 15% of
      studies had a placebo-type control group. Analyses by type of treatment showed
      that pulmonary rehabilitation (large muscle exercise and education plus a variety
      of psychosocial or behavioral interventions) had statistically significant
      beneficial effects on psychological well-being (d+ = 0.58, n = 13), endurance (d+
      = 0.77, n = 13), functional status (d+ = 0.63, n = 8), VO2 (d+ = 0.56, n = 5),
      dyspnea (d+ = 0.71, n = 10), and adherence (d+ = 1.76, n = 2). A statistically
      significant beneficial effect of pulmonary rehabilitation was not found on Forced
      Expiratory Volume at 1 s. Across 7 outcomes examined, treatments including
      education-alone had significant beneficial effect on the accuracy of performing
      inhaler skills (d+ = 1.27, n = 7). Based on a very small sample of studies, a non
      significant but small or medium sized effect of education-alone was evident on
      health care utilization (d+ = 0.26, n = 3) and on adherence to treatment regimen
      (d+ = 0.50, n = 2). Such results are inconclusive, suggesting that further
      research may be indicated. Relaxation-alone had statistically significant
      beneficial effects on both dyspnea (d+ = 0.91, n = 3) and psychological well
      being (d+ = 0.39, n = 6). The research base has methodological weaknesses that
      should be rectified in future research. Nonetheless, based on the best evidence
      available to date, identified types of psychoeducational care have been shown to
      improve the functioning and well-being of adults with COPD.

PMID- 9006232
TI  - Implementation of individualized patient education for Hispanic children with
      asthma.
AB  - An educational program known as the Childhood Asthma Project (CAP) was
      implemented to reduce morbidity among Hispanic children with chronic asthma.
      Seventy-three children, ages 6-16, participated in 4 program phases: baseline
      assessment, one-on-one child-centered education, application, and maintenance.
      During baseline assessment, child and parent asthma beliefs and behaviors were
      evaluated and used to create educational modules on symptom recognition, peak low
      meters, medications, and precipitating factors in Spanish and English. Children
      learned the importance of self-management, practiced using inhalers and peak flow
      meters and charted peak flow recordings. Videotapes provided peer modeling by
      showing Hispanic children with asthma performing self-management tasks. During
      the application phase, patients practiced self-management behaviors at home and
      reviewed progress with a nurse educator. During maintenance, the success of self
      monitoring was reviewed at follow-up appointments. Recommendations for designing
      health education interventions for Hispanic children are provided.

PMID- 9006234
TI  - Pain intensity and health locus of control: a comparison of patients with
      fibromyalgia syndrome and rheumatoid arthritis.
AB  - The major purpose of this study was to determine if 31 patients with fibromyalgia
      syndrome (FS) reported different pain intensity and Health Locus of Control (HLC)
      scores than 30 patients with rheumatoid arthritis (RA). Another purpose was to
      determine the relationship among experienced actual pain (present, usual, worse,
      least), recalled prior episodes of pain (worse toothache, headache, and stomach
      ache), HLC orientation, age and the duration of the actual pain. Visual Analogue
      Scales were used to measure pain intensity. The Health Locus of Control Scale was
      used to determine external/internal orientation. The results showed that the FS
      patients reported significantly more intense actual pain, recalled pain for worse
      toothache and headache, and were more externally oriented than the RA patients.
      Present pain intensity was significantly correlated to actual intensity ratings,
      but not to reported earlier experienced pain, except for worse stomach ache in
      the RA group. The findings' implications for treatment and education are
      discussed.

PMID- 9006236
TI  - The development of an interactive education program for heart failure patients:
      the Kodak Photo CD Portfolio concept.
AB  - Written information, as well as movie and video film, and computer programs have
      been used for information and education of patients. CD-ROM is now about to be
      used for the same purpose. The CD has several advantages over computer programs,
      such as high capacity and low production, duplication and distribution costs. It
      is unerasable and insensitive to electromagnetic forces. Heart failure (HF) is a
      common disease with poor prognosis. Due to diagnostic and treatment improvements
      new guidelines on evaluation and care of patients with HF have been published.
      Some advocate educational programs as a routine part of the care. Patients with
      HF (mostly elderly persons) use many drugs and need considerable education for
      effective self-care. To improve HF patients' knowledge of the disease and the
      drug treatment of the disease we have made an interactive, computer generated
      education program which is presented on a Kodak Photo CD Portfolio disc. The
      major steps and efforts in the development of the program, which uses a new
      principle, are explained, including some hardware and software issues. The
      program can be viewed on an ordinary TV set and run by the patients themselves.
      Unlike many educational products for health care professionals and patients, this
      product has now been included in a randomised patient education trial.

PMID- 9006235
TI  - Prehospital education: effectiveness with total hip replacement surgery patients.
AB  - In-hospital education can reduce anxiety, improve coping and shorten hospital
      stays of surgical patients. However, hospitals are containing costs by shortening
      pre- and postoperative stays and reducing the time available for in-hospital
      teaching. This study evaluated prehospital education for total hip replacement
      (THR) surgery. Half of the patients waiting for admission for THR surgery were
      randomly selected to receive a THR education booklet in the mail 4-6 weeks before
      their scheduled THR surgery. Compared to the No-Booklet patients, patients who
      had received the booklet were less anxious at the time of hospital admission and
      at discharge, were more likely to have practised physiotherapy exercises prior to
      hospitalization, and required significantly less occupational therapy and
      physiotherapy while in hospital. There were no group differences for length of
      hospital stay.

PMID- 9006238
TI  - To be a teacher, a tutor and a friend: the physician's role according to the
      Stockholm Diabetes Intervention Study (SDIS).
AB  - The Stockholm Diabetes Intervention Study (SDIS) showed that lower blood glucose
      levels led to halted or retarded microvascular complications in patients with
      insulin-dependent (type 1) diabetes mellitus (IDDM). Modern education was
      combined with tutoring, which led to improved blood glucose control in a
      randomized group of patients. In this setting, the expert-physician met and
      expert-patient in a mutual effort to make the patient able to live his daily life
      according to the wishes he had, without too much special consideration to the
      diabetes. The goals of the treatment were thus to improve the daily quality of
      life of the patient while keeping the HbA1c sufficiently low to avoid severe
      complications. The physician has to accept a new role as a teacher and tutor, and
      as such a caring but still professional friend.

PMID- 9006237
TI  - Psychosocial aspects of antiretroviral medication use among HIV patients.
AB  - This study examines variables related to alteration of antiretroviral medication
      regimens by HIV infected persons, independent of medical advice. Perceived
      severity, susceptibility, benefits/barriers, cues to action, and locus of control
      were included in the analyses. Of 99 subjects, 37 reported discontinuing
      antiretrovirals on their own initiative and 36 subjects ('fiddlers') reported
      recent alterations in their medication regimens. Subjects who reported greater
      perceived barriers and pessimism and less faith in the ability of antiretrovirals
      to protect them from AIDS related illness were more likely to discontinue drug
      therapy. Fiddlers were more pessimistic and perceived more barriers to drug
      therapy than compliers, who believed more in the benefits of antiretrovirals.
      Fiddlers were significantly more internally oriented than were discontinuers.
      Compliers were the most optimistic about the effect of antiretrovirals. Even
      though compliers were more symptomatic than discontinuers, they reported their
      health status to be better than did discontinuers.

PMID- 9006239
TI  - Outcome of two patient education methods on recruitment and compliance with
      ivermectin in the treatment of onchocerciasis.
AB  - Two patient education methods, Information Media (IM) and Social Network (SN),
      were compared to determine their relative effectiveness on recruitment and
      subsequent compliance behavior of people infected with onchocerciasis in respect
      of appointment keeping and ivermectin consumption in existing primary health care
      facilities in six communities in southwestern Nigeria. Two communities each were
      randomly assigned to the IM intervention group, two of the SN group, and two
      served as controls. A total of 1265 persons out of an estimated target population
      of 5033 infected individuals were enrolled in the study. Coverage rates were
      higher in the intervention communities (30.3% for SN and 29.9% for IM) than
      control (7.3%), but the differences between intervention groups was not
      significant. A drop-off was seen in attendance at the second round of ivermectin
      distribution. Nearly equal proportions of the intervention groups returned (43.3%
      for SN and 47.4% for IM), while few control patients came back for their second
      dose (12.3%). Factors responsible for the low turnout were thought to include the
      content of educational messages, mobility of community members and limited time
      available to collect the drugs. Cost considerations led to recommendations to
      maintain facility based distribution and the SN approach, with greater emphasis
      on mobilization to increase coverage and compliance.

PMID- 9006240
TI  - Determinants of compliance in men enrolled in a diet and exercise intervention
      trial: a randomized, controlled study.
AB  - Determinants of compliance with a 6-month diet and exercise program were studied
      among 118 healthy middle-aged men with risk factors for coronary heart disease
      (CHD). Data were gathered via medical examinations, interviews and
      questionnaires. Smoking, high levels of hostility, perception of barriers to diet
      change and low knowledge of risk factors for CHD were linked to poor compliance
      with increased intake of dietary fiber. Poor compliance with low fat diet was
      linked with smoking, younger age and not having relatives or friends afflicted
      with CHD. Poor compliance with the exercise program tended to be associated with
      younger age and having children at home. Practice implications for health
      professionals who provide clinical and educational services for middle-aged men
      with slightly elevated CHD risk factors are discussed.

PMID- 9006241
TI  - Psychoeducational training for schizophrenic patients: background, procedure and
      empirical findings.
AB  - As neuroleptic therapy alone still fails to other effective relapse prevention in
      schizophrenic patients, psychoeducational therapeutic approaches have been
      developed as an additional aid for patients and their families. This article
      details the central characteristics of these approaches. A psychoeducational
      group program for schizophrenic outpatients, the efficacy of which was
      investigated within the scope of a German controlled intervention study on 191
      patients, is also presented. The article describes in detail the methods used and
      the therapeutic objectives, reporting on changes in the attitudes of patients to
      their medication. At the end of the training program, patients who had attended
      regularly showed significantly better medication compliance and were more
      reserved with respect to their medication self-management. After 1 year the
      positive effects had diminished. However, booster sessions or participation of
      the psychiatrist in charge as group therapist would have had longer lasting
      effects.

PMID- 9006242
TI  - Effects of parental divorce and youth unemployment on adolescent health.
AB  - The aim of this study is to gain more insight into the effects of two important
      events on adolescent health in the life course of youngsters, namely parental
      divorce and being unemployed. We made use of the dataset of the Utrecht Study of
      Adolescent Development, a longitudinal panel study, based on a representative
      sample of young people in the Netherlands (12-24 years old). We used the data of
      non-school-going youngsters who are at least 18 years old. Parental divorce does
      indeed have negative effects on adolescent health: however, this applies only for
      girls. Being unemployed or having been unemployed has negative effects on
      psychological health, especially for boys. But this experience does not have
      negative effects on physical health, either for boys or girls. Any conclusions on
      the consequences of parental divorce and youth unemployment for adolescent health
      have to be specified, at least for sex.

PMID- 9006243
TI  - Assessment of perceived barriers in self-care of insulin-requiring diabetic
      patients.
AB  - To gain more insight into perceived barriers in the self-management of insulin
      treated diabetic patients, a cross-sectional study was conducted at our
      outpatient clinic. The Barriers in Diabetes Questionnaire (BDQ), consisting of
      three subscales, was completed by 240 patients (type I and II). Additional
      background information and medical data were gathered. Mean BDQ scores indicated
      that most barriers relate to 'self-regulation in specific situations'. No
      significant relationships were found between BDQ subscale-scores on the one hand
      and age, sex, educational level, type or duration of diabetes on the other.
      Patients with a higher HbA1c showed significantly higher scores on two of the
      three subscales. A significant negative correlation was found between patients'
      subjective evaluation of their health status and their BDQ-scores. It is
      concluded that the BDQ can be a valuable assessment tool for health care
      providers to tailor diabetes education and care to the patients' individual
      needs.

PMID- 9006244
TI  - Establishing the psychometric properties of a scale for evaluating quality in
      printed education materials.
AB  - A study establishing the psychometric properties of a quality standard for
      quantifying the presence (or absence) of instructional design/learning principles
      contained in printed education materials (PEMs) was conducted in 4 phases.
      Content validity, a pretest which included creation of a rating key, inter-rater
      reliability, and intra-rater reliability levels were established for the Bernier
      Instructional Design Scale (BIDS). Experts in patient education established
      content validity by identifying 37 instructional design/learning principles as
      essential to PEM quality from a 90 item domain. An inter-disciplinary group of 89
      health professionals applied the BIDS to a test PEM. Group ratings were compared
      with a rating key which served as a validated standard for the presence of
      principles in the test PEM. Reliability of the BIDS achieved acceptable levels
      when rating categories were collapsed from 4 to 3 levels to be consistent with a
      measurement model for rating checklists. A revised methodological approach and
      program of psychometric research are described.

PMID- 9006245
TI  - Pregnancy, alcohol use and the effectiveness of written health education
      materials.
AB  - This study was conducted to determine whether health education materials were
      more effective when written at a lower rather than a higher reading level. Women
      (n = 252) who visited public health maternity clinics selected either English- or
      Spanish-language health designed to discourage alcohol use, depending on whether
      the women preferred to read English or Spanish. The materials were written on the
      third and the 10th-grade reading levels. The women were randomly assigned to
      receive materials written on one of the two levels. Then participants completed
      the pre-test, read the health education material and were post-tested
      immediately. Among English-speaking participants, the material written at the
      lower reading level was shown to be more effective. Whereas among Spanish
      speaking participants, test scores were unchanged after reading either health
      education material. Overall, we recommend that health care providers design or
      purchase materials that are easy-to-read and provide face-to-face counseling
      about abstaining from alcohol. Providers should not rely on written materials to
      communicate important messages when working with pregnant women.

PMID- 9006246
TI  - ANA sells publishing subsidiary: PNA members get free subscription to AJN.

PMID- 9006247
TI  - UAP curriculum available from the American Association of Critical-Care Nurses.

PMID- 9006248
TI  - Must the CNE approval application process be so difficult?

PMID- 9006249
TI  - Janice Weinberg's career clinic. Using a professional resume service.

PMID- 9006250
TI  - [Hospital nursing conducted according to Rogers' theory. The participating
      process of human field patterning in a clinical environment].
AB  - The participating process of human field patterning in an acute-care environment
      Scientific story-telling is the basis of this article, which describes the care
      of a patient within the conceptual framework of Martha Rogers. Dr. Mary Madrid, a
      nurse at New York University Hospital and a student of Rogers, describes the
      continuous process of intentional pattern changes of the human energy field. The
      human energy field finds itself in an ongoing, mutual and integral process with
      the environmental energy field. Madrid elucidates in this way that the human
      energy field is integral to a continuous, mutual process of becoming and
      enfolding with the universe. The theory of Barrett, derived from Rogers' "Science
      of unitary human beings" is applied. Furthermore, nursing interventions congruent
      with Rogers' system are being described. These are therapeutic touch, guided
      visualisation, music therapy as well as breathing and relaxation exercises. This
      scientific story of Madrid is an excellent example of Rogers' science-based
      nursing.

PMID- 9006253
TI  - [Helping patients to die--an ethical challenge to nursing care and to its
      institutional framework].
AB  - The current discussion about the moral legitimacy of euthanasia is primarily
      concerned with the question of to what extent passive and active forms of
      euthanasia (limited legalized practice in the Netherlands) can actually be
      distinguished from one another. From a nursing perspective this passive/active
      distinction appears in a completely different way: with regard to varied
      conditions which would have to be fulfilled to favour another "culture of dying",
      in which the desire to terminate life no longer appears as the drastic
      alternative to a principally curative or maximum therapeutic oriented care system
      for the afflicted. For this purpose, new orientations within the nursing
      professions which equally combine instrumental, psychosocial, institutional and
      educational aspects, are necessary. Applied to problems of euthanasia, questions
      of a fundamental ethical structure in nursing appear within an enlarged
      framework.

PMID- 9006252
TI  - [Power or its absence in nursing].
AB  - Power is required to obtain professional goals. The aim of this study is to
      clarify the significance of power and the lack of it in the opinions of nurses
      and in prevailing nursing practice. The power of the nurse was measured by the
      nurse's own assessment of her/his capability to improve the quality of nursing
      care. The data were collected from all the registered nurses (n = 179) of five
      hospitals. The response was 70%. The powerful nurses had more knowledge, were
      better motivated, implemented policies more often, acted consciously towards
      nursing goals and collaborated better than the powerless nurses. The results
      demonstrated that nurses who had enough power possessed both wider and deeper
      cognitive and moral dimensions and had better skills in human interaction than
      did the powerless nurses.

PMID- 9006254
TI  - [Emergency nurses investigate their patients' needs].
AB  - This article reports on a study in which clinical nurses contributed actively to
      the scientific investigation of the nursing needs of their patients. The study
      revealed valuable information relating to both the psycho-social needs caused by
      the accident and the integration of nurses in clinical nursing research.

PMID- 9006255
TI  - [Freedom versus safety].
AB  - Nurses maintain frequently that freedom and safety are, to a great extent,
      mutually exclusive in the care of elderly patients. On hand of reflected personal
      experience and an analysis of literature this article will show 1. how painful
      limiting restrictions, and especially restraining measures, can be for patients,
      relatives and nurses, and 2. that modern nursing has various instruments and
      methods to ensure almost invariably freedom and safety.

PMID- 9006256
TI  - [Effects of soft bedding on body perception and posture].
AB  - This investigation in several hospitals of the Federal Republic of Germany
      attempts for the first time to demonstrate the effects of soft bedding on the
      patients' condition on hand of well known and in other disciplines well
      established criteria. It could be shown that the softness of the mattress causes
      considerable problems for the patient. Furthermore, it becomes clear that the
      extent of nursing increases markedly with a very soft bedding of the patient in
      order to compensate for the disadvantages arising from it. Materials used in the
      prevention of bed sores (so called antidecubitus mattresses) have to be evaluated
      critically. Nurses must attempt to determine which kind of mattress ought to be
      used. If the mobility of the patient is not to be restricted even more, the use
      of a harder mattress may have to be considered.

PMID- 9006257
TI  - [Quality assurance and standardized measures--a critical discussion].
AB  - The debate about quality and quality assurance has a long tradition in the market
      economy. New in the Federal Republic of Germany, however, is the debate about
      "quality" in the human services sector: in medical and nursing care, in hospitals
      and the community, in the health service. This discussion presents practising
      professionals, politicians and scientists with a number of unsolved problems.
      This is especially so in defining quality but also in developing, implementing
      and evaluating appropriate instruments of quality assurance. Quality is far more
      than what is intended by legislation-economy, productivity and competition- and
      often conflicts with these expectations. As a consequence, the process of
      discussion about defining quality turns out to be vague and contradictory rather
      than systematic, especially since quality cannot be seen as a static component
      but must be explored as a dynamic element. It is high time to start a critical
      debate about the concept of quality and current methods of quality assurance.

PMID- 9006260
TI  - [The importance of hygiene].

PMID- 9006258
TI  - [Qualitative versus quantitative research methods: paradigmatic alternatives--an
      issue in nursing?].
AB  - This discussion of alternative methodologies arises from research conducted in
      1994 about the development and determinants of satisfaction in basic nursing
      education. In this project qualitative approaches were used to allow a comparison
      of the results with those achieved by standardised quantitative investigations.
      Besides the fact that satisfaction in basic nursing education has so far been
      investigated predominantly with quantitative methods which limit the responses of
      the subjects from the outset, critics in the field of occupational research have
      pointed to the necessity of using qualitative methods in investigating job
      satisfaction. Following a historical review of the methodological debate in the
      social sciences, a presentation of fundamental aspects and criteria of
      quantitative and qualitative methods and a detailed description of the research
      strategy used in the above project, a comparison of the results will attempt to
      answer the research question.

PMID- 9006261
TI  - [Tasks of a hygiene expert--theory versus practice?].

PMID- 9006262
TI  - [Nursing in the Ukraine].

PMID- 9006263
TI  - [Knowledge and power in nursing].

PMID- 9006264
TI  - [Medicine and conscience. The Congress of International Physicians for the
      Prevention of Nuclear War says No to euthanasia].

PMID- 9006265
TI  - [Nursing and care of patients in chemotherapy. 1].

PMID- 9006266
TI  - Nursing career satisfaction: the effects of autonomy, social integration and
      flexible scheduling.

PMID- 9006267
TI  - Career options--the increasing demand for courtroom nurses.

PMID- 9006269
TI  - Surfing nurses (or fun on the Internet).

PMID- 9006268
TI  - Envisioning nursing's future.

PMID- 9006270
TI  - Specialisation and credentialling in nursing.

PMID- 9006271
TI  - [Reflections on the interpersonal relations during the care of a terminal
      patient].

PMID- 9006272
TI  - [Nursing in anesthesia and intensive care. Safety at the work place--legal
      implications].

PMID- 9006273
TI  - [What all women should know about menopause].

PMID- 9006274
TI  - [Hypertension in children].

PMID- 9006275
TI  - [Reports from other countries--Finland. Occupational health nurses in Finland].

PMID- 9006276
TI  - Nurses take the lead in HIV/AIDS care.

PMID- 9006277
TI  - A journey of parenting a child with HIV.

PMID- 9006278
TI  - Living with open hearts.

PMID- 9006279
TI  - HIV infected RN launches national campaign for safer needle technologies.

PMID- 9006280
TI  - Resources for HIV and AIDS services or information.

PMID- 9006281
TI  - Nurses and politics: what can we gain?

PMID- 9006282
TI  - Peer assistance. Focus on new return-to-work opportunities for nurses in
      recovery.

PMID- 9006283
TI  - School nurses and children's health.

PMID- 9006285
TI  - Biophysical characteristics of radiofrequency lesion formation in vivo: dynamics
      of catheter tip-tissue contact evaluated by intracardiac echocardiography.
AB  - During clinical radiofrequency catheter ablation a wide range of delivered power
      may be necessary to achieve success despite an apparently stable catheter
      position on fluoroscopy. The purpose of this study was to use intracardiac
      echocardiography to characterize the relation between catheter tip-tissue contact
      and the efficiency of heating during applications of radiofrequency energy in
      vivo and to determine whether intracardiac echocardiography could be used
      prospectively to improve tissue contact. A closed-loop temperature feedback
      control system was used during radio-frequency applications at five anatomic
      regions in the right atrium of 15 anesthetized dogs to ensure achievement of a
      predetermined temperature (70 degrees C) at the catheter tip thermistor by
      automatic adjustment of delivered power (maximum 100 W). The efficiency-of
      heating index was defined as the ratio of steady-state temperature (degrees
      Celsius) to power (watts). Two-dimensional intracardiac echocardiography was used
      to evaluate movement of the catheter tip relative to the endocardium.
      Perpendicular contact was scored as good, average, or poor and lateral catheter
      sliding as < 2, 2 to 5, or > 5 mm. Two groups of animals were included: group 1,
      in which tissue contact was guided by fluoroscopic and electrographic criteria
      for stability of contact, with intracardiac echocardiography used simply to
      observe the application; and group 2, in which tissue contact was guided by
      intracardiac echocardiography. Of 66 applications, 18 (27.3%) had poor
      perpendicular contact on echocardiography, and 12 (18.2%) demonstrated lateral
      sliding of > 5 mm even though they had been considered to have good tissue
      contact by fluoroscopic and electrographic criteria. Perpendicular catheter
      contact and anatomic location were shown to be independently related to the
      efficiency-of-heating index. Applications with good perpendicular contact had a
      significantly higher efficiency-of-heating index and a significantly greater
      lesion size than those with average or poor contact. The percentage of
      applications having good perpendicular tissue contact and the lesion size were
      significantly greater when tissue contact was guided by intracardiac
      echocardiography compared with fluoroscopic and electrographic guidance. This
      study demonstrates that variations in catheter tip-tissue contact account for
      differences in the efficiency of tissue heating, independently of the anatomic
      site of the application. Poor tissue contact was observed by intracardiac
      echocardiography and confirmed by indexes of tissue heating in approximately one
      third of radiofrequency applications despite a fluoroscopic appearance and
      electrographic morphologic appearance suggestive of good tissue contact. There
      was a significant correlation between echocardiographic evaluation of tissue
      contact, parameters of tissue heating (efficiency-of-heating index), and lesion
      size. In addition, intracardiac echocardiography could be used prospectively to
      improve the percentage of good contact applications and increase the lesion size.

PMID- 9006284
TI  - Are soft echoes really soft? Intravascular ultrasound assessment of mechanical
      properties in human atherosclerotic tissue.
AB  - To examine the accuracy of intravascular ultrasound (IVUS) in assessing the
      biophysical properties of atherosclerotic plaque, 33 human iliac arteries were
      imaged with a 25 MHz IVUS transducer and classified into four groups on the basis
      of IVUS appearance: minimally diseased arterial wall, bright echogenic plaque
      with acoustic shadowing, bright echogenic plaque without shadowing, and
      hypoechogenic plaque (so-called "soft echoes"). The hardness of each plaque was
      assessed with an ultrasensitive compression ergonometer. The radial static stress
      strain relations fit well (r > 0.98) to exponential curves, providing a
      compression stiffness constant (K) defined as the coefficient of the exponential
      power. K for bright echogenic plaque with shadowing was significantly greater
      than that of the other tissues. However, K among minimally diseased entire
      arterial wall, hypoechogenic plaque, and bright echogenic plaque without
      shadowing was not significantly different, but these tissues are not physically
      soft compared with adipose tissue. Therefore, tissue characterization by IVUS
      distinguishes calcified from noncalcified plaque and accurately predicts its
      biomechanical hardness. However, soft echoes, although less firm than calcium, do
      not necessarily correspond to soft tissue.

PMID- 9006286
TI  - Requirement for accurate measurement of regurgitant stroke volume by the combined
      continuous-wave Doppler and color Doppler flow convergence method.
AB  - The examination conditions necessary for accurate measurement of regurgitant
      volume by the proximal flow convergence method applying a simple hemispheric
      equation remain uncertain. This study investigated the requirement for measuring
      regurgitant stroke volume from the combined continuous-wave and color Doppler
      proximal flow convergence approach. Twenty-five pulsatile flow rates were
      produced by driving five regurgitant stroke volumes ranging from 30 to 70 ml/beat
      through planar orifices with cross-sectional areas ranging from 0.10 to 1.0 cm2.
      Four different shaped orifices (circular, rectangular with a major/minor axis
      ratio 2:1, slitlike with a major/minor axis ratio of 8:1, and square) having
      identical orifice areas (0.5 cm2) were examined. Regurgitant volume (RV) was
      estimated from the combined continuous-wave and color Doppler approach according
      to the previously described equation RV = 2 pi x (r max)2 x AV x (TVI/Vmax),
      where r max is maximal radial distance, AV is aliasing velocity, TVI is time
      velocity integral of regurgitant jet, and Vmax is peak velocity of regurgitant
      jet. Plotting the difference between actual and calculated RV versus radial
      distance of the proximal convergence shell for each flow rate from circular to
      rectangular orifices yielded curves conforming to a curvilinear function that
      crossed the point of zero difference at 1.0 cm. However, in the slitilke orifice,
      a more remote distance (1.6 cm) is required for the best agreement. Actual
      regurgitant stroke volume can be estimated well by the combined continuous-wave
      Doppler and proximal flow convergence method applying a simple hemispheric
      equation if an aliasing velocity is used that results in a radial distance of at
      least 1.0 cm.

PMID- 9006287
TI  - Coronary plaque morphologic characteristics early and late after heart
      transplantation: in vivo analysis with intravascular ultrasonography.
AB  - To characterize plaque morphologic characteristics of transplant coronary artery
      disease early and late after cardiac transplantation, 72 patients were studied
      with intravascular ultrasonography during routine coronary angiography (group 1,
      25 patients < or = 2 months after surgery; group 2, 47 patients > or = 12 months
      after surgery). Both groups had comparable baseline characteristics. Three
      hundred fifty-one segments were imaged in 127 coronary arteries (4.9 +/- 1.8
      segments per patient). By intravascular ultrasonography, relevant intimal
      thickening (> 0.3 mm) was found in the majority of patients (68% for group 1 and
      72% for group 2). Angiography detected abnormal findings in only 16% and 32% for
      groups 1 and 2, respectively. Mean intimal index was higher in patients late
      after transplantation (27% +/- 12% vs 17% +/- 12%, respectively; p < 0.01).
      Maximal and mean plaque thickness were comparable in both groups, whereas a
      higher mean plaque circumference was found in group 2 (278 +/- 66 degrees vs 211
      +/- 75 degrees, respectively; p < 0.002). The lesions were more eccentric in
      patients early after transplantation (mean eccentricity index 95% +/- 7% vs 77%
      +/- 15%, respectively; p < 0.0001). Diffuse, concentric intimal thickening was
      not a common pattern. Maximal plaque thickness correlated with donor age (r =
      0.50, p < 0.0001). Coronary lesions were frequent even early after
      transplantation, with predominantly eccentric plaque morphologic characteristics
      indicative of preexisting atherosclerosis. Later after transplantation, a more
      homogeneous plaque distribution was seen, partly with diffuse concentic intimal
      thickening. Late transplant coronary artery disease appears to be a combination
      of preexisting native and acquired immune-mediated coronary artery disease.

PMID- 9006288
TI  - Diabetes mellitus and echocardiographic left ventricular function in free-living
      elderly men and women: The Cardiovascular Health Study.
AB  - This report describes the relation among diabetes, blood pressure, and prevalent
      cardiovascular disease, and echocardiographically measured left ventricular mass
      and filling (transmitral valve flow) velocities in the Cardiovascular Health
      Study, a cohort of 5201 men and women > or = 65 years of age. Ventricular septal
      and left posterior wall thicknesses were greater in diabetic than in nondiabetic
      subjects, showing a significant linear trend (p = 0.025 for ventricular septal
      thickness in both sexes combined, p = 0.002 for posterior wall thickness) with
      increased duration of diabetes. Increased wall thickness of the ventricular
      septum or the left posterior wall was not associated with prevalent coronary
      heart disease (CHD) in the cohort. Increased left ventricular mass was associated
      with diabetic persons not reporting CHD and with all subjects with CHD regardless
      of glucose tolerance status. After adjusting for body weight, blood pressure,
      heart rate, and prevalent coronary or cerebrovascular disease, diabetes (as
      measured by glucose level, insulin use, oral hypoglycemic use, and a positive
      history of diabetes before baseline examination) remained an independent
      predictor of increased left ventricular mass among men and women (174.2 gm in
      diabetic men vs 169.8 gm in normal men, 138.2 gm in diabetic women vs 134.0 gm in
      normal women, p = 0.043 for both sexes combined). Both early and late diastolic
      transmitral peak flow velocities were higher with increased duration of diabetes,
      but the calculated ratio of the early peak flow velocity to the late velocity
      (E/A ratio) did not differ significantly between subjects with historical
      diabetes and those with normal fasting glucose (both genders combined, p =
      0.190). Glucose level, insulin use, oral hypoglycemic use, and a positive history
      of diabetes before baseline examination were significant independent predictors
      of the late transmitral peak flow velocity and its integrated flow-velocity curve
      but not for the integral of the early peak flow velocity or the E/A ratio.
      Diabetes is associated with abnormal left ventricular structure and function in
      elderly persons. This association persists after adjustment for body weight,
      blood pressure, heart rate, and reported coronary or cerebrovascular disease.

PMID- 9006289
TI  - Determination of coronary flow measurements by transesophageal echocardiography:
      dependence of flow velocity reserve on the location of stenosis.
AB  - Doppler velocimetry with the use of transesophageal echocardiography can record
      flow in the proximal left anterior descending artery (LAD). To assess whether
      this limited sampling ability influences the recording of velocity and the
      calculation of coronary flow reserve (CFR), 32 patients with LAD stenosis (4
      ostial stenoses, 18 proximal stenoses, 10 mid-LAD stenoses) and 33 patients with
      arteriographically normal LADs were studied. Basal flow and dipyridamole-induced
      hyperemic flow rates were recorded. The mean basal flow velocity in ostial
      stenoses was greater than in other groups, and the mean basal flow velocity in
      proximal stenoses was less than that in mid-LAD stenoses and in the normal group.
      Maximal hyperemic velocity did not differ between the groups. CFR in all stenoses
      groups was less than that in the normal group. Ostial CFR was less than in all
      other groups, and proximal CFR was less than that in either the mid-LAD or the
      normal LAD groups. With this technique, coronary flow velocimetry and estimation
      of CFR is affected by the location of stenosis.

PMID- 9006290
TI  - Effects of physiologic load of pregnancy on left ventricular contractility and
      remodeling.
AB  - Left ventricular (LV) adaptation to the hemodynamic load of pregnancy has been
      studied with load-sensitive ejection-phase indexes, but the results of these
      studies are conflicting. The aim of this study was to examine the effects of the
      hemodynamic load of pregnancy on the contractile state of the left ventricle by
      using load-adjusted indexes of contractility. Thirty-four healthy women were
      prospectively studied by serial echo and Doppler examinations at six periods
      during pregnancy and after delivery. LV volume increased 10.5%, paralleling the
      change in stroke volume. End-systolic stress, an index of myocardial afterload,
      decreased 28.8% because of a decrease in end-systolic pressure and an increase in
      LV thickness/diameter ratio. Despite the increase in preload and the decrease in
      afterload, ejection phase indexes did not change during or after pregnancy.
      Although remaining within the normal range, the afterload-adjusted velocity of
      circumferential fiber shortening, an index of contractility that is relatively
      insensitive to preload, transiently decreased by 1.75 SDs during gestation,
      returning to non-pregnant values 2 to 4 weeks postpartum. Thus the increase in
      hemodynamic load that characterizes normal pregnancy is associated with
      preservation of global pump function. The transient decrease in contractile state
      may represent an adaptation phase of the contractile elements of the myocardium
      to the rapid changes in loading conditions observed during the first trimester of
      pregnancy.

PMID- 9006291
TI  - Heterogeneous aortic response to acute beta-adrenergic blockade in Marfan
      syndrome.
AB  - Although prophylactic treatment with beta-blockers is used to retard aortic root
      dilatation in Marfan syndrome, it is not effective in all patients. To assess the
      effects of beta-adrenergic blockade on the aorta's elastic properties, aortic
      stiffness index and distensibility were calculated in 13 patients with Marfan
      syndrome and 10 control subjects before and after beta-adrenergic blockade. At
      baseline, patients with Marfan syndrome had a significantly increased stiffness
      index and decreased distensibility. After beta-adrenergic blockade, 8 patients
      with Marfan syndrome developed stiffness indexes and distensibility values that
      were closer to normal, whereas these variables deteriorated in 5 patients. Thus
      the benefit of beta-adrenergic blockade in Marfan syndrome may be the reduction
      in pulse pressure and myocardial contractility and also promotion of the elastic
      properties of the aorta. Moreover, the differential responses of aortic mechanics
      (normalizing or worsening) to beta-adrenergic blockade may possibly have
      implications for the prognosis in these patients.

PMID- 9006292
TI  - Percutaneous double-valve balloon valvotomy for multivalve stenosis: immediate
      results and intermediate-term follow-up.
AB  - Ten patients each with combined mitral and tricuspid stenosis (group 1) and with
      combined mitral and aortic stenosis (group 2) underwent double-valve balloon
      valvotomy as a single staged procedure. The aortic valve was dilated by the
      Mansfield balloon technique, whereas the mitral and tricuspid valves were dilated
      with either the Mansfield or Inoue balloon. The mitral valve area increased from
      0.78 +/- 0.21 cm2 to 2.05 +/- 0.56 cm2 (p < 0.0005) in group 1 and from 0.75 +/-
      0.20 cm2 to 2.1 +/- 0.59 cm2 (p < 0.05) in group 2. The tricuspid valve area
      increased from 1.11 +/- 0.41 cm2 to 2.52 +/- 0.69 cm2 (p < 0.0005). In group 2,
      the transaortic gradient decreased from 93.56 +/- 17.7 mm Hg to 28.56 +/- 7.8 mm
      Hg (p < 0.0005) and the valve area increased from 0.37 +/- 0.05 cm2 to 1.03 +/-
      0.25 cm2 (p < 0.005). The excellent symptomatic and hemodynamic results were
      sustained at 30.3 +/- 9.8 months of follow-up in group 1 and at 23.5 +/- 9.1
      months in group 2. Double-valve balloon valvotomy is feasible and safe and
      provides excellent immediate and intermediate-term follow-up results in selected
      patients with multivalve disease. A longer follow-up in a larger number of cases
      is needed to define further the role of this therapy.

PMID- 9006293
TI  - Transesophageal Doppler echocardiographic assessment of systolic and diastolic
      coronary blood flow velocities at baseline and during adenosine triphosphate
      induced coronary vasodilation in chronic aortic regurgitation.
AB  - Few reports exist on the changes in systolic and diastolic coronary flow
      velocities (CFVs) at baseline and during coronary vasodilation in patients with
      chronic aortic regurgitation (AR). We examined the left anterior descending CFVs
      in 21 patients with AR (11 patients with mild AR and 10 patients with moderate to
      severe AR), 9 patients without AR (no AR group), and 6 patients who had undergone
      surgery for moderate to severe AR (postoperation group) with transesophageal
      Doppler echocardiography. Adenosine triphosphate (ATP) was infused into a
      peripheral right arm vein at four different doses (35, 70, 100, and 140
      micrograms/kg/min). Coronary flow velocity response in systole and diastole was
      calculated as the ratio of systolic peak and mean and diastolic peak and mean
      CFVs during maximal ATP infusion to those at baseline. The systolic peak and mean
      CFVs and the diastolic peak and mean CFVs at baseline were significantly
      increased in the moderate to severe group compared with those in the other groups
      (p < 0.05, respectively). Systolic and diastolic CFVs were significantly
      increased during ATP infusions in the four groups. No significant differences of
      systolic and diastolic CFVs were observed among the four groups during maximal
      ATP infusion. The coronary flow velocity response calculated from the peak and
      mean diastolic CFVs were significantly decreased in the moderate to severe group
      (1.6 +/- 0.3 and 1.7 +/- 0.4) compared with those in the other three groups (3.6
      +/- 0.7 and 3.2 +/- 1.1 in the no AR group, 2.6 +/- 0.6 and 2.5 +/- 0.4 in the
      mild group, and 2.5 +/- 0.7 and 2.4 +/- 0.6 in the postoperation group) (p <
      0.05, respectively). In conclusion, the systolic and diastolic left CFVs at
      baseline appeared to be significantly increased in patients with moderate to
      severe chronic AR. However, the velocities during coronary vasodilation by ATP
      were equal to those in other groups, resulting in a decrease of coronary flow
      velocity response in systole and diastole.

PMID- 9006294
TI  - Pharmacologic stress-induced regional myocardial blood flow heterogeneity and
      left ventricular wall thickening abnormality: comparison of intravenous adenosine
      with dipyridamole in a model of critical coronary stenosis.
AB  - Variations in reported sensitivity of myocardial perfusion scans or wall motion
      abnormalities during pharmacologic stress with intravenous adenosine and
      dipyridamole may be caused by differences in myocardial oxygen demand or
      myocardial blood flow redistribution induced by each agent. To investigate the
      physiologic correlates of functional abnormalities during pharmacologic stress
      testing, regional myocardial blood flow (radiolabeled microsphere technique) and
      left ventricular segmental wall thickening (quantitative two-dimensional
      echocardiography) were measured in 9 dogs with an open chest model of critical
      stenosis of the left circumflex coronary artery. Data were obtained at baseline
      and peak drug infusion for intravenous adenosine (0.42 mg/kg over a 3-minute
      period) and for intravenous dipyridamole (0.56 mg/kg over a 4-minute period).
      Adenosine and dipyridamole induced regional flow abnormality in 7 (77%) of 9
      dogs. Myocardial segments with decreased endocardial/epicardial flow ratio were
      similar for both agents (2.9 +/- 1.8 vs 2.7 +/- 1.3, p = [NS]). Segments with
      myocardial flow heterogeneity (ratio of endocardial flow to control left anterior
      descending/left circumflex endocardial flow) were similar for both agents (2.7 +/
      0.9 vs 2.3 +/- 1.0, p = NS). Adenosine-induced wall thickening abnormality (77%
      vs 55% with dipyridamole) correlated with regional flow abnormality.
      Significantly lower mean arterial pressure (53 +/- 1.7 mm Hg vs 64 +/- 1.9 mm Hg,
      p < 0.01) and more prolonged drug effect (18 +/- 6.4 min vs 3 +/- 1.4 min, p <
      0.001) were seen for dipyridamole compared with adenosine. Adenosine induces
      regional flow abnormality similar to dipyridamole but with less hemodynamic
      perturbation, and adenosine-induced wall thickening abnormality more closely
      parallels regional flow abnormality.

PMID- 9006295
TI  - Importance of left ventricular diastolic function on maintenance of exercise
      capacity in patients with systolic dysfunction after anterior myocardial
      infarction.
AB  - To investigate the role of left ventricular (LV) diastolic function in the
      maintenance of exercise capacity in patients with systolic dysfunction, symptom
      limited cardiopulmonary exercise testing combined with radionuclide
      ventriculography was performed in 24 patients with an LV ejection fraction < 35%
      after anterior myocardial infarction. The ratio of pulmonary artery wedge
      pressure (PAWP) to LV end-diastolic volume (EDV), an index of global diastolic
      function, correlated significantly with peak oxygen consumption at peak exercise
      (r = -0.55; p = 0.006), whereas ejection fraction at peak exercise did not. The
      change in PAWP/EDV ratio from rest to peak exercise was related to the increases
      in stroke volume (r = -0.54; p = 0.006) and cardiac output (r = -0.51; p = 0.01)
      during exercise, but the change in ejection fraction was not. Resting
      hemodynamics did not differ between patients with preserved exercise capacity
      (group 1, n = 8) and those with exercise impairment (group 2, n = 16). At peak
      exercise, stroke volume, cardiac output, and EDV were significantly higher, and
      PAWP and PAWP/EDV ratio were significantly lower in group 1 than in group 2, but
      ejection fraction and end-systolic volume were similar in both groups. Although
      the incidences of hypertension, LV hypertrophy, and infarct-related coronary
      artery lesions did not differ between the two groups, group 2 had a significantly
      higher incidence of non-infarct-related coronary artery lesions than group 1 (p <
      0.05). Thus in patients with LV systolic dysfunction after anterior myocardial
      infarction, the major cause of exercise impairment and failure to increase LV
      performance during exercise was diastolic dysfunction associated with the
      presence of non-infarct-related coronary artery lesions with the potential for
      exercise-induced ischemia of the noninfarcted areas.

PMID- 9006296
TI  - Increased renal formation of thromboxane A2 and prostaglandin F2 alpha in heart
      failure.
AB  - Renal formation of the vasoconstrictor prostaglandins thromboxane A2 (TXA2) and
      prostaglandin F2 alpha (PGF2 alpha) was investigated in 25 patients with cardiac
      failure, divided into New York Heart Association functional classes I to IV, and
      in eight healthy control subjects. Plasma renin activity (PRA) and hemodynamic
      parameters were also investigated. Renal vasoconstrictor eicosanoid formation,
      measured in urinary daily excretion, was not different between patients in class
      I and control subjects. Class II to IV patients showed progressively increasing
      production of PGF2 alpha (F = 49.8, p < 0.001, analysis of variance) and TXA2 (F
      = 37.8, p < 0.002). PGF2 alpha excretion peaked in class IV (+ 1266% vs class I,
      p < 0.001). Compared with class I, urinary excretion of thromboxane B2 was + 816%
      in class III and + 1561% in class IV (both p < 0.001). PRA was significantly
      increased only in class IV (+ 1558%, p < 0.001). The current results indicate a
      progressive increase in renal production of vasoconstrictor eicosanoids directly
      related to New York Heart Association class and suggest that these prostanoids
      may have a role in deterioration of renal function.

PMID- 9006297
TI  - Low-energy intracardiac shocks during atrial fibrillation: effects on cardiac
      rhythm.
AB  - The effect on ventricular rate of intracardiac shocks for atrial fibrillation was
      studied in 13 patients receiving 95 shocks. Shocks were synchronized to the R
      wave and were delivered after R-R intervals > 500 msec, with increasing strength
      (20 to 400 V). In 10 patients, conversion to sinus rhythm was achieved in this
      way. Noneffective shocks increased the mean first postshock R-R interval
      (compared with 20 V as baseline), for shocks > or = 140 V. The R-R prolongation
      correlated with the shock level (r = 0.936, p < 0.01). Subsequent R-R intervals
      were comparable to baseline. A similar trend toward longer first postshock
      intervals was observed for effective shocks. However, the maximal first R-R
      interval after noneffective shocks had no relation to the voltage. The number of
      pauses > 1500 msec tended to increase with voltage (noneffective shocks). Pauses
      > 2500 msec were exceptional (4 of 85 noneffective shocks). No symptomatic
      bradycardia occurred. In subsequent intervals (cycles 2 through 10) no pauses >
      2500 msec were noted. It is concluded that atrial defibrillation attempts between
      the right atrium and coronary sinus prolong R-R intervals, in relation to
      administered energy, but without the need for backup pacing.

PMID- 9006298
TI  - QT interval prolongation and risk of life-threatening arrhythmias during
      toxoplasmosis prophylaxis with spiramycin in neonates.
AB  - We recently reported two cases of QT interval prolongation and cardiac arrest in
      newborns receiving antibiotic therapy with spiramycin, a macrolide agent
      extensively used for toxoplasmosis prophylaxis. In this study we assessed the
      effects of this drug on ventricular repolarization and on the potential risk of
      lethal arrhythmias in eight newborn infants in whom toxoplasmosis prophylaxis
      after birth was necessary. Electrocardiograms (ECGs) and echocardiograms were
      recorded during spiramycin therapy (350,000 i.u./kg/ day) and after its
      withdrawal. In a control group of eight healthy newborns matched for age and sex,
      no differences were found between two ECGs analogously recorded. The QT interval
      corrected for heart rate (QTc) was longer during spiramycin therapy than after
      drug withdrawal (448 +/- 32 msec vs 412 +/- 10 msec, +9%, p = 0.021). QTc
      dispersion, expressed as the difference between the longest and the shortest
      value in 12 different leads (QTcmax-min), was also higher during spiramycin
      therapy (60 +/- 32 msec vs 34 +/- 8 msec, +76%, p = 0.021), mainly because of a
      major lengthening of the longest QTc (QTcmax). QTc and QTc dispersion were
      markedly increased in the two newborns who experienced cardiac arrest after
      beginning treatment compared with the six neonates who had no drug-induced
      symptoms. During therapy seven of eight newborns had a rare abnormality in the
      thickening of the left ventricular posterior wall similar to that observed in
      patients with congenital long QT syndrome. This abnormality disappeared after
      drug withdrawal. Thus antibiotic therapy with spiramycin in the neonatal period
      may induce QT interval prolongation and increase QT dispersion. When this effect
      on ventricular repolarization is more marked, it may favor the occurrence of
      torsades des pointes and lead to cardiac arrest.

PMID- 9006299
TI  - Aneurysm of the membranous ventricular septum resulting in pulmonary outflow
      tract obstruction in congenitally corrected transposition of the great arteries.
AB  - Aneurysm of the membranous ventricular septum causing subpulmonic obstruction in
      patients with corrected transposition is rare but well documented. Higher left
      sided (morphologic right) ventricular pressure causes protrusion of the aneurysm
      into the pulmonary outflow tract of the right-sided morphologic left ventricle,
      causing obstruction related to lack of conus and proximity of the aneurysm to
      subpulmonary region. Echo Doppler studies and angiography are useful in making a
      correct diagnosis. Surgical resection of the aneurysm along with closure of the
      ventricular septal defect is the treatment of choice. The prognosis is likely to
      be excellent.

PMID- 9006300
TI  - Evaluation of mitral valve prolapse by four-dimensional echocardiography.
AB  - To observe the stereoscopic structure and the motion of the prolapsing mitral
      valve and its regurgitant jet in comparison with the normal mitral valve, four
      dimensional (or dynamic three-dimensional) echocardiography of mitral valve
      apparatus was obtained in 20 patients with mitral valve prolapse and 10
      unaffected subjects by use of transthoracic and transesophageal methods. The
      normal mitral valve apparatus has a consistent saddle-shaped configuration, with
      its anterior and posterior high points located near the aortic root and posterior
      left ventricular wall, respectively, and its low points located medially and
      laterally. In mitral valve prolapse, the spatial relation of mitral leaflets and
      anulus can be observed in four dimensions either from the left ventricle toward
      the left atrium or from the left atrium toward the left ventricle; the position,
      size, shape, motion, and extent of functional abnormality of the prolapsing
      mitral valve were clearly displayed. On the long-axis view of the left ventricle
      and the apical four-chamber view of four-dimensional echocardiography, the part
      of prolapsing mitral valve that protruded into the left atrium appeared as a
      spoon-like depression. We also obtained four-dimensional images of regurgitant
      blood flow to observe the stereoscopic view of blood flow column and its cross
      sectional area, spatial position, and dynamic changes. This technique is of great
      value in evaluating patients with mitral valve prolapse, increasing the
      diagnostic sensitivity and specificity, and giving assistance to the surgeons in
      making preoperative therapeutic decisions and assessing the intraoperative and
      postoperative results.

PMID- 9006301
TI  - Neonatal supraventricular tachycardia: predictors of successful treatment
      withdrawal.

PMID- 9006302
TI  - Congenital cardiomyopathy associated with human parvovirus B19 infection.

PMID- 9006303
TI  - Aneurysm of saphenous vein bypass graft detected by first-pass radionuclide
      ventriculography.

PMID- 9006304
TI  - Our vision for the American Heart Journal.

PMID- 9006305
TI  - Risk factors for kidney damage in the adult population of Wadena, Minnesota. A
      prospective study.
AB  - An increased albumin excretion rate (AER) is associated with impaired glucose
      tolerance and diabetes mellitus in some populations, but data on Americans of
      Northern European origin are lacking. In 1986-1987, AER and creatinine clearance
      were measured in 455 adults in a survey of the population of Wadena, Minnesota.
      Thirty-five subjects (8%) had an AER > or = 15 micrograms/minute, and eight of
      these had overt proteinuria (AER > or = 175 micrograms/minute). AER and
      creatinine clearance were uncorrelated except when AER was increased. Unadjusted
      mean AER in a stratified random sample of adults (n = 374) was 3.6
      micrograms/minute. Adjusted values for 277 subjects with normal glucose tolerance
      and for 80 subjects with impaired glucose tolerance were very similar (3.8 and
      3.7 micrograms/minute, respectively), whereas mean AER was 5.4 micrograms/minute
      for persons with non-insulin-dependent diabetes mellitus (NIDDM) who were not
      taking insulin and 9.4 micrograms/minute for persons with NIDDM who were taking
      insulin (p < 0.0001). After adjustment for age, mean creatinine clearance was
      unrelated to glucose tolerance. Systolic blood pressure was a major determinant
      of increased AER (p < 0.0001) and lowered creatinine clearance (p = 0.0011),
      independently of diabetes. AER was stable over 5 years among the 321 cases who
      were not taking insulin and were not severely hypertensive. The decrease in
      creatinine clearance was greater in ex-smokers and current smokers than in
      nonsmokers. The authors conclude that hypertension and NIDDM were independently
      associated with the risk of kidney damage in this population, as indicated by a
      higher AER. High-normal blood pressure, but not impaired glucose tolerance, was
      associated with microalbuminuria. These relatively mild changes may reflect an
      ethnically based resistance to the damaging effects of hyperglycemia on the
      kidney. Smoking may accelerate the aging-related decline in glomerular filtration
      rate.

PMID- 9006306
TI  - Effects of smoking on the incidence of non-insulin-dependent diabetes mellitus.
      Replication and extension in a Japanese cohort of male employees.
AB  - The effects of smoking on the 8-year (1984-1992) incidence of non-insulin
      dependent diabetes mellitus (NIDDM) were investigated in a cohort of 2,312 male
      employees of an electrical company in Japan. The incidence rate was 2.2/1,000
      person-years. After controlling for other known risk factors for NIDDM, a
      proportional hazards regression analysis indicated that those who were currently
      smoking 16-25 cigarettes per day had a 3.27 times higher risk of developing NIDDM
      during the follow-up period than never smokers (p < 0.05); the hazard ratio was
      similar (3.21) for those who were currently smoking > or = 26 cigarettes per day.
      Among ever smokers, proportional hazards regression analysis also indicated that
      younger age at starting smoking was associated with an increased risk of NIDDM (p
      for trend = 0.09). These findings suggest that number of cigarettes smoked per
      day is important in the relation between smoking and NIDDM incidence, although
      the risks did not increase above a given amount of smoking. Starting smoking at a
      younger age also might be independently associated with an increased risk of
      NIDDM.

PMID- 9006307
TI  - Smoking, nicotine dependence, and depressive symptoms in the CARDIA Study.
      Effects of educational status.
AB  - The present study was designed to determine whether depressive symptoms are
      independently associated with smoking and nicotine dependence among cigarette
      smokers, using 1990-1991 data from the Coronary Artery Risk Development in Young
      Adults (CARDIA) Study. A total of 3,933 participants (788 black men, 1,090 black
      women, 974 white men, and 1,081 white women) aged 23-35 years were included.
      Analyses were stratified by race and sex. Depressive symptoms were measured by
      means of the Center for Epidemiologic Studies Depression (CES-D) Scale. Nicotine
      dependence was defined as smoking one's first cigarette of the day within 30
      minutes of awakening. Analysis of covariance was used to control for potential
      covariates (age, body mass index, alcohol consumption, and education). In
      unadjusted comparisons, smokers had more depressive symptoms than never smokers
      in all groups except white men; this relation showed little change after
      adjustment for age, body mass index, and alcohol consumption. However, after
      adjustment for education in addition to the above variables, these differences
      became attenuated and were significant only among white women (adjusted CES-D
      score difference = 1.9, p < 0.02). When analyses were further stratified by
      nicotine dependence, dependent smokers had higher CES-D scores than never smokers
      in all groups. The differences again became attenuated when education was added
      to the model, and were significant only among black women (adjusted CES-D score
      difference = 2.3, p < 0.01). These results indicate that although smoking in
      general and nicotine-dependent smoking in particular are related to symptoms of
      depression, controlling for educational level attenuates these relations.

PMID- 9006308
TI  - Dietary factors and the incidence of hip fracture in middle-aged Norwegians. A
      prospective study.
AB  - Dietary data from a prospective study were used to relate factors influencing
      calcium balance (estimates of dietary calcium intake, protein intake from
      nondairy animal sources (meat, fish, and eggs), and coffee consumption) to the
      incidence of hip fracture. During the years 1977-1983, women and men born between
      1925 and 1940 and living in one of three Norwegian counties were invited to a
      cardiovascular screening that included a dietary survey. The attendance rate at
      screening was 91.1%, and 90.7% of these persons (19,752 women and 20,035 men)
      filled in and returned a semiquantitative dietary questionnaire. This cohort was
      followed for an average of 11.4 years (range, 0.01-13.8 years) with respect to
      hip fracture, defined as cervical or trochanteric fracture. During follow-up, 213
      hip fractures were identified, excluding fractures associated with high-energy
      trauma and metastatic bone disease. There was no clear association between
      calcium intake or nondairy animal protein intake and hip fracture in this cohort.
      However, an elevated risk of fracture was found in women with a high intake of
      protein from nondairy animal sources in the presence of low calcium intake
      (relative risk = 1.96 (95% confidence interval 1.09-3.56) for the highest quarter
      of nondairy protein intake and the lowest quarter of calcium intake vs. the three
      lower quarters of protein intake and the three higher quarters of calcium
      intake). Women who drank nine or more cups of coffee per day also had an
      increased risk of fracture, while there was no association between coffee
      consumption and hip fracture in men. Although these findings do not necessarily
      imply causal relations, they suggest the presence of risk factors for hip
      fracture that act through a negative calcium balance in this population.

PMID- 9006309
TI  - Prospective study of the determinants of age at menopause.
AB  - The authors prospectively studied the effect of demographic, reproductive, stress
      related, and health behavior factors measured at study entry on age of natural
      menopause in 185 healthy US women. At study entry, women were 42.5-47.5 years old
      and premenopausal. After a baseline examination (1983-1985), women were followed
      for 7-9 years, during which time they reported on a monthly basis their menstrual
      status and whether they were taking hormones. Menopausal age was defined as age
      at the last menstrual period prior to stopping menstruation for 12 months (and
      not taking hormones). Estimated median age at menopause was 51.5 years for the
      whole sample. Median age at menopause was earlier for women who reported
      irregular menstrual cycles at study entry (50.2 years), were African-American
      (49.3 years), were smokers (50.6 years), or were currently on a weight reduction
      diet (50.5 years). Psychosocial stress was predictive of an even earlier median
      age at menopause in African Americans (48.4 years) and in those with irregular
      cycles at baseline (49.4 years). Results suggest that premenopausal women in
      their forties who are experiencing irregular menstrual cycles, are smokers, are
      dieting, or are African-American are likely to reach menopause earlier than their
      contemporaries. African-American women may have a different "biological clock"
      than white women, especially when under stress, or they may experience more
      stress of longer duration.

PMID- 9006310
TI  - Epidemiologic study of Down syndrome in a racially diverse California population,
      1989-1991.
AB  - The prevalence of Down syndrome was studied among all live births occurring
      between 1989 and 1991 in the California counties monitored by the California
      Birth Defects Monitoring Program. Objectives of this study were: 1) to calculate
      adjusted prevalence rates and quinquennial maternal age-specific risk rates of
      Down syndrome after adjusting for elective abortion of prenatally diagnosed
      fetuses; 2) to estimate the impact of prenatal diagnosis and subsequent elective
      abortion of affected fetuses on the observed prevalence of Down syndrome; and 3)
      to examine sex ratios among liveborn infants and fetuses with Down syndrome. The
      racial/ethnic diversity and large size of the population allowed the data to be
      stratified into five racial categories-Hispanics, whites, Asians, blacks, and
      others. For the period 1989-1991, the observed prevalence of Down syndrome was
      1.13 per 1,000 live births, and the adjusted total prevalence, which took into
      account the termination of affected pregnancies following prenatal diagnosis, was
      1.53 per 1,000 live births. In a comparison of quinquennial maternal age-specific
      risk rates of Down syndrome by race, Hispanics and whites were the only groups
      with rates that differed significantly from each other, with Hispanics exhibiting
      higher rates at maternal ages under 40 years. The overall reduction in live
      births with Down syndrome in 1989-1991 that could be attributed to prenatal
      diagnosis and elective abortion of affected fetuses was 25.8%, with a 49.1%
      reduction being observed at maternal ages > or = 35 years. In 1990-1991,
      Hispanics had the lowest overall reduction (10.0%), while whites had the highest
      reduction (46.3%). The male: female ratios among liveborns with Down syndrome
      were significantly higher than those among all live births, and race had a
      significant association with sex ratios in both cases and controls. These
      findings indicate that prenatal diagnosis and elective termination of affected
      pregnancies has had a substantial impact in reducing the number of liveborns with
      Down syndrome in the monitored California counties. The effect was greatest for
      whites and least for Hispanics, with results indicating considerable variation in
      the use of prenatal diagnostic services among racial/ethnic groups. Estimates of
      adjusted total prevalence and reduction in live births with Down syndrome in this
      study should be considered minimal because of some underascertainment of
      prenatally diagnosed cases.

PMID- 9006311
TI  - Impact of Asian ethnicity and national origin on infant birth weight.
AB  - To investigate the relation between Asian ethnicity/national origin and low birth
      weight (< 2,500 g), the authors analyzed singleton live births among 50,044 Asian
      and 221,866 white women who delivered in California during 1992. Ethnic and
      subgroup differences in prenatal characteristics and birth weight outcomes were
      found between Asian and white women and between Asian subgroups. In unadjusted
      comparisons, very low birth weight (500-1,499 g) was more likely among Filipino
      women and less likely among Chinese women, relative to whites. Moderately low
      birth weight (1,500-2,499 g) was more likely among Cambodian, Filipino, Indian,
      Japanese, Laotian, and Thai women and was less likely among Koreans, relative to
      whites. In multivariate analyses, Filipino women remained at increased risk of
      both very low and moderately low birth weight, while Cambodian, Indian, and
      Laotian women had elevated odds of moderately low birth weight. Chinese women
      were less likely to have very low birth weight infants than were whites.
      Utilization of prenatal care was also associated with low birth weight. Perinatal
      outcomes among Asians vary by national origin, and accepted risk factors that
      were studied only partially explain this variation.

PMID- 9006312
TI  - Asymptomatic and symptomatic cryptosporidiosis: their acute effect on weight gain
      in Peruvian children.
AB  - This study investigated whether a child's first infection with Cryptosporidium
      parvum had an acute effect on weight gain. Specifically, the authors compared
      monthly rates of weight gain between C. parvum-infected and noninfected children.
      Over a 2-year period (1989-1991), a cohort of Peruvian children aged 0-3 months
      at recruitment were followed twice weekly for assessment of daily diarrheal
      status, weekly for C. parvum stool examinations, and monthly for anthropometric
      measurements. Data on 207 children permitted the authors to examine the effect of
      C. parvum infection on weight gain. During the 2-year study period, 45% (94/207)
      of the children became infected with C. parvum for the first time. Weight gain
      intervals in 57 of the 94 infected children met criteria for analysis. Of these,
      63 percent (36/57) were asymptomatic (i.e., had no diarrhea). On average,
      children with symptomatic cryptosporidiosis gained (i.e., grew) 342 g less (95%
      confidence interval 167-517) during the first month of infection than did
      children without diarrhea who were not yet infected. The effect of asymptomatic
      cryptosporidiosis was less severe: On average, children with asymptomatic
      infection gained 162 g less (95% confidence interval 27-297) during the first
      month of infection than did children without diarrhea who were not yet infected.
      Symptomatic cryptosporidiosis retarded weight gain more than did asymptomatic
      cryptosporidiosis, but the latter was twice as common. Since asymptomatic
      cryptosporidiosis is more prevalent, it may have more of an overall adverse
      effect on child growth in the community than symptomatic cryptosporidiosis.

PMID- 9006314
TI  - Identification of a cohort of male and female twins aged 65 years or more in the
      United States.
AB  - In this paper, a method with which to identify a national cohort of elderly twins
      is proposed. Record linkage algorithms were developed and applied to the > 30
      million records contained in the Medicare beneficiary file. The matching
      algorithm for male/male pairs used race (black or white), last name, date of
      birth, and state of issuance of the Social Security number. Female/female and
      male/female pairs were selected with matching on race, date of birth, and the
      first seven digits of the Social Security number to compensate for the absence of
      maiden names. A stratified random sample of same-sex and opposite-sex white and
      black pairs (six groups) were selected and surveyed for determination of the
      actual prevalence of twins. On the basis of these results, the authors conclude
      that this method could identify an estimated 18,308 male/male, 7,544
      female/female, and 204 male/female pairs of twins aged 65 years or more. This
      would be the largest sample of older twins ever assembled in the United States
      and represents a significant new resource for epidemiologic studies of the aging
      population.

PMID- 9006313
TI  - Development of oral lesions in human immunodeficiency virus-infected transfusion
      recipients and hemophiliacs.
AB  - The authors used multivariate repeated-measures transition models to identify
      risk factors for two oral lesions related to human immunodeficiency virus (HIV)
      candidiasis and hairy leukoplakia-in 152 HIV-infected blood transfusion
      recipients and hemophiliacs. Subjects were examined for occurrences of these
      lesions every 6 months from July 1985 through March 1993, yielding 1,076 study
      visits. It was found that, after adjustment for the CD4:CD8 T-lymphocyte ratio,
      patients with a history of candidiasis in the previous 18 months were at high
      risk of lesion recurrence. This risk increased with the number of prior episodes
      and with the recency of the episode(s). A history of hairy leukoplakia was less
      predictive of persistence of that lesion after adjustment for significant risk
      factors (including candidiasis and use of antifungal agents at the current
      examination, a low CD4:CD8 cell ratio, and age less than 40 years). The authors
      also found a high coprevalence of candidiasis and hairy leukoplakia in these
      subjects. These results suggest that HIV-infected patients with oral candidiasis
      should be carefully monitored for subsequent episodes over the next 12-18 months,
      and patients with either oral candidiasis or hairy leukoplakia and a low CD4:CD8
      cell ratio should be carefully examined for the other type of lesion as well.

PMID- 9006315
TI  - Measurement error correction for logistic regression models with an "alloyed gold
      standard".
AB  - Recently, some authors have questioned the validity of methods which correct
      relative risk estimates for measurement error and misclassification when the
      "gold standard" used to obtain information about the measurement error process is
      itself imperfect. When such an "alloyed" gold standard is used to validate the
      usual exposure measurement, the bias in the "regression calibration" (Rosner et
      al., Stat Med 1989; 8:1051-69) measurement-error correction factor for relative
      risks estimated from logistic regression models is derived. This quantity is a
      function of the correlations of the "alloyed" gold standard (X) and the usual
      exposure assessment method (Z) with the truth, of the ratio of the variances of X
      and Z, and of the correlation between the errors in the "alloyed" gold standard
      and the errors in the usual exposure assessment method. In this paper, it is
      proven that if the errors between Z and X are uncorrelated, the regression
      calibration method has no bias even when the gold standard is "alloyed." When a
      third method of exposure assessment is available and it is reasonable to assume
      that the errors in this method are uncorrelated with the errors in the other two
      exposure assessment methods, point and interval estimates of the correlation
      between the errors in X and Z are derived. These methods are illustrated here
      with data on the measurement of physical activity, vitamins A and E, and poly-
      and monounsaturated fat. In addition, when a third exposure assessment method is
      available, a modification of standard regression calibration is derived which can
      be used to calculate point and interval estimates of relative risk that are
      corrected for measurement error in both X and Z. This new method is illustrated
      here with data from the Health Professionals Follow-up Study, a study
      investigating the associations between physical activity and colon cancer
      incidence and between vitamin E intake and coronary heart disease. It is shown
      that in these examples, correlations of the errors in X and Z tended to be small.
      Even when moderate, estimates of relative risk corrected for error in both X and
      Z were not very different from the estimates which assumed that X was a true gold
      standard.

PMID- 9006317
TI  - Expression of the G2-M checkpoint regulators cyclin B1 and cdc2 in nonmalignant
      and malignant human breast lesions: immunocytochemical and quantitative image
      analyses.
AB  - We investigated the in vivo expression of cyclin B1 and Cdc2 (key molecules for
      G2-M transition during the cell cycle) in nonmalignant and cancerous human breast
      lesions using immunohistochemistry and quantitative proliferative index (PI)
      analysis. Breast epithelial cells co-expressed cyclin B1 and Cdc2 in their
      cytoplasm in the G2 phase and in their nuclei in the M phase. Cyclin B1, but not
      Cdc2, immunostaining rapidly disappeared from the nuclei during the mitotic
      metaphase to anaphase transition. Static image analysis revealed the mean
      proliferative index for cyclin B1/cdc2 for each type of lesion to be as follows:
      normal glands (n = 20), 2.0/2.5%; benign lesions, including typical ductal
      hyperplasia (n = 76), 2.5/5.8%; atypical ductal hyperplasia (n = 21), 3.0/6.6%;
      carcinomas in situ (n = 70), 7.4/14.0%; and invasive carcinomas (n = 58),
      10.0/22.9%. Proliferative index data for atypical hyperplasia were virtually
      identical to those for benign lesions and were significantly lower than those for
      breast cancer, suggesting that expression levels of cyclin B1 and Cdc2 may be
      used to distinguish premalignant human breast lesions from advanced disease.
      Furthermore, the proliferative index for cyclin B1 for comedo-type ductal
      carcinomas in situ agreed with that for invasive ductal carcinomas (mean, 10.1%
      versus 9.5%), apparently explaining the clinicopathological aggressiveness of
      this tumor at the molecular level.

PMID- 9006318
TI  - Localization of the cell proliferation and apoptosis-associated CAS protein in
      lymphoid neoplasms.
AB  - We have evaluated the expression and distribution of the cellular apoptosis
      susceptibility (CAS) protein in normal lymphoid tissue and malignant lymphomas.
      CAS protein, the product of the CAS gene, is associated with microtubules and the
      mitotic spindle. Immunohistochemistry with an antibody to CAS shows many CAS
      positive cells in normal tonsils. The majority of strongly CAS-positive cells
      were localized to the dark zone of the follicles, whereas the mantle zone and
      interfollicular areas were essentially negative. Double staining for CAS and Ki
      67 revealed co-expression of the two proliferation markers in approximately 85 to
      90% of the CAS-positive cells. Different subtypes of lymphomas exhibited varying
      patterns of CAS expression. Low-grade non-Hodgkin's lymphoma generally revealed
      weak staining with CAS, with 10 to 60% of all cells being positive. In contrast,
      highly malignant non-Hodgkin's lymphoma and malignant cells of Hodgkin's disease
      displayed very strong CAS positivity, with staining of up to 80% of the atypical
      cells. Overall, the staining pattern of CAS and Ki-67 was superimposable within a
      particular lymphoma subtype. However, in all lymphomas we observed a significant
      fraction of CAS-positive normal and malignant lymphocytes that were Ki-67
      negative, probably because they were momentarily noncycling cells. We conclude
      that a high expression of CAS correlates with proliferation of normal and
      malignant lymphoid cells. The fact that detection of CAS protein identifies a
      higher portion of proliferating and malignant cells than Ki-67 warrants further
      evaluation of CAS protein as a marker with a diagnostic potential.

PMID- 9006316
TI  - Tumors associated with p53 germline mutations: a synopsis of 91 families.
AB  - Although inherited p53 mutations are present in all somatic cells, malignant
      transformation is limited to certain organs and target cells. The analysis of 475
      tumors in 91 families with p53 germline mutations reported since 1990 shows that
      breast carcinomas are most frequent (24.0%), followed by bone sarcomas (12.6%),
      brain tumors (12.0%), and soft tissue sarcomas (11.6%). The sporadic counterparts
      of these tumors also carry a high incidence of p53 mutations, suggesting that in
      these tissues p53 mutations are capable of initiating the process of malignant
      transformation. Hematological neoplasms (acute lymphoblastic leukemia and
      Hodgkin's lymphoma) and adrenocortical carcinomas occurred at a frequency of 4.2
      and 3.6%, respectively. One-half of the families fulfilled the diagnostic
      criteria of the Li-Fraumeni syndrome. There were marked organ-specific
      differences in the mean age at which carriers of p53 germline mutations present
      with neoplastic disease: 5 years for adrenocortical carcinomas, 16 years for
      sarcomas, 25 years for brain tumors, 37 years for breast cancer, and almost 50
      years for lung cancer. Analysis of the mutational spectrum showed a predominance
      of G:C-->A:T transitions at CpG sites, suggesting an endogenous formation, eg, by
      deamination of 5-methylcytosine, rather than a causation by environmental
      mutagenic carcinogens. The location of mutations within the p53 gene was found to
      be similar to that of somatic mutations in sporadic tumors. There is no evidence
      of an organ or target cell specificity of p53 germline mutations; the occasional
      familial clustering of certain tumor types is more likely to reflect the genetic
      background of the respective kindred or the additional influence of environmental
      and nongenetic host factors.

PMID- 9006319
TI  - Expression of the receptor for complement C5a (CD88) is up-regulated on reactive
      astrocytes, microglia, and endothelial cells in the inflamed human central
      nervous system.
AB  - C5a receptor (C5aR, CD88) is a receptor originally described on neutrophils and
      monocyte-macrophages but recently found on hepatocytes, epithelial cells,
      endothelial cells, and tissue mast cells. We recently reported that human fetal
      astrocytes expressed a functional C5aR in vitro. Here we examine C5aR expression
      in adult brain cultures by immunostaining with six different anti-C5aRs and show
      that C5aR is expressed constitutively by astrocytes, microglia, and fibroblast
      like cells but not by oligodendrocytes. In fetal brain cultures we confirmed that
      astrocytes constitutively expressed C5aR and demonstrated that fetal microglia
      and fibroblast-like cells but not oligodendrocytes and neurones expressed C5aR.
      Incubation with inflammatory cytokines (interferon gamma, interleukin-1, and
      tumor necrosis factor alpha) or phorbol ester failed to induce or up-regulate
      C5aR expression on fetal or adult brain cells. Immunohistochemistry was performed
      to determine the expression and distribution of C5aR in the normal and inflamed
      brain. In the normal brain C5aR was minimally expressed, whereas in inflamed
      brains from a variety of pathologies, C5aR expression was greatly up-regulated on
      reactive astrocytes and microglia and to a lesser extent on endothelial cells. We
      propose that expression of C5aR is a marker of central nervous system
      inflammation, and that C5aR expression on brain cells in inflammation plays an
      important role in cell activation and recruitment (gliosis).

PMID- 9006320
TI  - Expression of the TSC2 product tuberin and its target Rap1 in normal human
      tissues.
AB  - The tuberous sclerosis-2 (TSC2) gene is linked to tuberous sclerosis (TSC), a
      dominantly inherited genetic syndrome in which inactivation of the normal TSC2
      allele is associated with the development of mostly benign tumors and focal
      dysplasias. TSC2 encodes the protein tuberin, which is a widely expressed 180-kd
      polypeptide that exhibits specific GTPase activating activity toward Rap1 in
      vitro and co-localizes with Rap1 in cultured cells. In this study, we have
      performed immunohistochemical analyses, using affinity-purified anti-tuberin
      antibodies, to study the distribution of tuberin in a panel of normal human
      organs that are commonly affected by TSC. Cryosections indicated that tuberin is
      widely expressed at low levels. More intense staining of tuberin, in the
      cryosections and in paraffin sections, was observed in the small blood vessels of
      many organs, including the kidney, skin, and adrenal gland. High levels of
      tuberin were also detected in cortical neurons and cerebellar Purkinje cells.
      These findings imply that loss-of-function mutations in TSC2 might lead to the
      development of highly vascularized tumors, subcortical tubers, and focal atrophy
      of the cerebellar cortex, which are features commonly associated with TSC.
      Moreover, Rap1 was also found to be highly expressed in many of the same cells
      that contained high levels of tuberin, suggesting a functional interaction
      between tuberin and Rap1 in these tissues.

PMID- 9006321
TI  - Activation of matrix metalloproteinase-2 from hepatic stellate cells requires
      interactions with hepatocytes.
AB  - Activation of matrix metalloproteinase (MMP)-2, the 72-kd collagenase
      IV/gelatinase A, is involved in extracellular matrix remodeling. It has been
      suggested that a membrane-type MMP (MT-MMP-1) and the tissue inhibitor of
      metalloproteinase (TIMP)-2 are involved in MMP-2 processing, but the exact
      mechanism(s) of its activation remains unclear. We have investigated the role of
      cell-cell cooperation in the activation of pro-MMP-2 in the liver, using pure
      cultures and co-cultures of hepatocytes and hepatic stellate cells (HSCs).
      Northern blot analysis and in situ hybridization showed that, in both pure and co
      cultures, HSCs, but not hepatocytes, expressed MMP-2, TIMP-2, and MT-MMP-1 mRNA.
      Zymography analyses revealed the latent form of MMP-2 in medium from 2-day-old
      pure HSC cultures with higher amounts in medium from hepatocyte/HSC co-cultures.
      When hepatocytes were added to 10-day-old HSC cultures, the activated form of MMP
      2 was detected, concomitantly with the deposition of an abundant extracellular
      matrix. Incubation of plasma membrane-enriched fractions from hepatocytes with
      conditioned medium from pure HSC cultures generated the activated species of MMP
      2 (62 and 59 kd). Activation of pro-MMP-2 by hepatocyte membranes was inhibited
      by EDTA, heat, and trypsin but not by serine proteinase inhibitors. These data
      show that the co-expression of TIMP-2, MMP-2, and MT-MMP-1 by HSCs does not lead
      to secretion of the activated form of MMP-2. Hepatocytes, which do not express
      MMP-2, TIMP-2, or MT-MMP-1, induce MMP-2 activation through a plasma membrane
      dependent mechanism(s), thus suggesting that cell-cell interactions are involved
      in this process in vivo.

PMID- 9006322
TI  - Overexpression of granulocyte-macrophage colony-stimulating factor induces
      pulmonary granulation tissue formation and fibrosis by induction of transforming
      growth factor-beta 1 and myofibroblast accumulation.
AB  - We have previously reported that transfer to rat lung of the granulocyte
      macrophage colony-stimulating factor (GM-CSF) gene leads to high expression of GM
      CSF between days 1 and 4 and granulation tissue formation followed by an
      irreversible fibrotic response starting from day 12 onward. In the current study,
      we investigated the underlying mechanisms. We found that GM-CSF overexpression
      did not enhance production of tumor necrosis factor-alpha in a significant manner
      at any time after GM-CSF gene transfer. However, the content of transforming
      growth factor-beta 1 in bronchoalveolar lavage fluid was markedly induced at day
      4 and appeared to be maximal around day 7 and remained high at day 12.
      Macrophages purified from bronchoalveolar lavage fluid 7 days after GM-CSF gene
      transfer spontaneously released significant quantities of transforming growth
      factor-beta 1 protein in vitro. After peak transforming growth factor-beta 1
      production was the emergence of alpha-smooth muscle actin-rich myofibroblasts.
      Accumulation of these cells was most prominent at day 12 within the granulation
      tissues and they were still present in fibrotic areas between days 12 and 24 and
      diminished markedly afterward. Thus, we provide the first in vivo evidence that
      tumor necrosis factor-alpha may be dissociated from participation in a fibrotic
      process in the lung and GM-CSF may play a more direct role in pulmonary
      fibrogenesis at least in part through its capability to induce transforming
      growth factor-beta 1 in macrophages and the subsequent emergence of myofibroblast
      phenotypes. This GM-CSF transgene lung model is useful for a stepwise dissection
      of both cellular and molecular events involved in pulmonary fibrosis.

PMID- 9006323
TI  - Prolactin-derived amyloid in the aging pituitary gland.
AB  - Small amyloid deposits occur commonly in different organs in association with
      aging. As in other amyloids, the fibrils in the age-associated forms are built up
      by specific proteins, unique to every histological type. The amyloid proteins
      that have been identified in localized amyloid of human endocrine organs have all
      been of polypeptide hormone nature, and these include calcitonin, islet amyloid
      polypeptide (amylin), and atrial natriuretic factor. In the present study, we add
      prolactin to the increasing group of known amyloid proteins and show that this
      hormone constitutes the amyloid fibrils of pituitary glands of aging individuals.

PMID- 9006324
TI  - Microsatellite instability is uncommon in uterine serous carcinoma.
AB  - Thirty-four uterine serous carcinomas, a type of endometrial carcinoma with
      aggressive behavior and a high frequency (90%) of p53 gene mutations, were
      analyzed for microsatellite instability (MI). Genomic DNA isolated from paired
      normal and tumor tissue was analyzed at eight microsatellite loci (D2S119,
      D2S123, D2S147, D10S197, D13S175, D18S58, D18S69, and ATn) located on four
      different chromosomes. All 34 tumors failed to meet the criteria for MI, defined
      as an alteration in the size of at least two of the microsatellite loci in tumor
      DNA when compared with normal DNA. Only three tumors demonstrated a shift in the
      size of a single microsatellite locus. Previously we reported MI in 20% of
      uterine endometrioid carcinomas, the most common type of endometrial carcinoma.
      The observed difference in the MI frequency between endometrioid and serous
      carcinoma is statistically significant (P = 0.003). Our data demonstrate that MI
      is uncommon in uterine serous carcinoma and support that different pathogenetic
      mechanisms are involved in the development of the two most common types of
      endometrial carcinoma.

PMID- 9006325
TI  - Gain of chromosome 17 is the most frequent abnormality detected in neuroblastoma
      by comparative genomic hybridization.
AB  - Neuroblastoma behavior is variable and outcome partially depends on genetic
      factors. However, tumors that lack high-risk factors such as MYCN amplification
      or 1p deletion may progress, possibly due to other genetic aberrations.
      Comparative genomic hybridization summarizes DNA copy number abnormalities in a
      tumor by mapping them to their positions on normal metaphase chromosomes. We
      analyzed 29 tumors from nearly equal proportions of children with stage I, II,
      III, IV, and IV-S disease by comparative genomic hybridization. We found two
      classes of copy number abnormalities: whole chromosome and partial chromosome.
      Whole chromosome losses were frequent at 11, 14, and X. The most frequent partial
      chromosome losses were on 1p and 11q. Gains were most frequent on chromosome 17
      (72% of cases). The two patterns of gain for this chromosome were whole 17 gain
      and 17q gain, with 17q21-qter as a minimal common region of gain. Other common
      gains were on chromosomes 7, 6, and 18. High level amplifications were detected
      at 2p23-25 (MYCN region), at 4q33-35, and at 6p11-22. Chromosome 17q gains were
      associated with 1p and/or 11q deletions and advanced stage. The high frequency of
      chromosome 17 gain and its association with bad prognostic factors suggest an
      important role for this chromosome in the development of neuroblastoma.

PMID- 9006327
TI  - Immunobead filtration: a novel approach for the isolation and propagation of
      tumor cells.
AB  - We have developed a method to facilitate the isolation and expansion of tumor
      cells from body fluids and tissue biopsies. Antibody-conjugated magnetic beads
      (immunobeads) were used to isolate tumor cells from blood, bone marrow,
      ascitic/pleural fluids, and enzyme-digested tissue biopsies. Filtration of the
      resulting cell suspension through a 20-micron nylon monofilament filter secured
      to the base of polystyrene 96-well strips purged the bead-rosetting cell fraction
      of contaminating normal cells and unbound beads. Tumor cells that bound the
      magnetic beads were retained on the membrane due to their increased size and
      concentrated into a small area (0.332 cm2), thus maintaining a high cell density.
      The filters provided a stable and uniform three-dimensional matrix for cell
      growth, with a total surface area of 1.42 cm2 available for cell attachment. The
      filters could be easily removed from the base of the 96-well strips to facilitate
      handling and transfer between culture vessels. Tumor cells grown on the filters
      could subsequently be harvested using trypsin/EDTA or left in situ for
      immunostaining with conventional immunohistochemical procedures. Filter-grown
      cells have shown extended passage in conventional cell culture in six cases. In
      two of five cases, the orthotopic implantation of confluent filters that
      contained approximately 10(4) cells/8 x 8 mm filter successfully produced tumors
      in nude mice after only 4 weeks. Our new approach may be of value in improving
      the success rate of generating long-term cultures from previously unproductive
      sources of tumor cells and thus may yield a greater variety of cell lines/strains
      for the study of malignant disease.

PMID- 9006326
TI  - T cell receptor-alpha beta-deficient mice fail to develop colitis in the absence
      of a microbial environment.
AB  - Mice with null mutations in cytokine or T cell receptor (TCR) genes develop
      intestinal inflammation. In the case of interleukin-2-/- and interleukin-10-/-
      mice it has been demonstrated that normal intestinal bacterial flora can cause
      gut pathology. TCR-alpha-/- mice not only develop colitis but also produce a
      strong antibody response to self-antigens, such as double-stranded DNA. It is
      therefore important to establish whether the intestinal inflammation develops
      spontaneously or is induced by luminal antigens. To address this issue, a germ
      free colony of TCR-alpha-/- mice was derived and compared with TCR-alpha-/- mice
      kept in conventional specific-pathogen-free conditions. Although specific
      pathogen-free animals developed colitis with a high level of penetrance, there
      was no evidence of intestinal pathology in germ-free animals. Furthermore,
      intestinal inflammation was not seen in TCR-alpha-/- mice colonized with a
      limited bacterial flora consisting of Lactobacillus plantarum, Streptococcus
      faecalis, S. faecium, and/or Escherichia coli. We conclude that intestinal
      inflammation in TCR-alpha-/- mice does not occur spontaneously nor does it result
      from the presence of bacteria, per se, but rather it is initiated by a specific
      organism or group of organisms normally present in the gut flora that have yet to
      be identified.

PMID- 9006328
TI  - In vivo spontaneous neuronal to neuroendocrine lineage conversion in a subset of
      neuroblastomas.
AB  - Neuroblastoma is an embryonal tumor derived from the sympathetic nervous system.
      Although all neuroblastomas have a neuronal character, a subset of tumors also
      show evidence of extra-adrenal neuroendocrine differentiation in discrete cell
      layers. A characterization of the cells of the developing human sympathetic
      nervous system was performed, identifying growth-associated protein-43,
      neuropeptide tyrosine, and Bcl-2 as marker genes for sympathetic neurons. Whereas
      all neuroblastomas express growth-associated protein-43, neuropeptide tyrosine,
      and Bcl-2, tumors with differentiating cells with neuroendocrine features
      expressed these genes only in the morphologically immature, proliferating cells.
      Thus, with neuroendocrine tumor cell differentiation, neuronal marker gene
      expression vanished and proliferation ceased and was succeeded by expression of
      chromogranin A/B and insulin-like growth factor-2, markers of neuroendocrine
      chromaffin differentiation. These tumors appear to provide examples of
      spontaneous lineage conversion from a neuronal to a neuroendocrine phenotype.

PMID- 9006329
TI  - Apoptotic-like changes in Lewy-body-associated disorders and normal aging in
      substantia nigral neurons.
AB  - In Parkinson's disease and other Lewy-body-associated disorders, the substantia
      nigra pars compacta undergoes degeneration, but the mechanism of cell death has
      not been previously described. The substantia nigra of normal and Alzheimer's
      disease cases were compared with substantia nigra from patients with Lewy-body
      associated disorders (Parkinson's disease, concomitant Alzheimer's/Parkinson's
      disease, and diffuse Lewy body disease) using in situ end labeling to detect
      fragmented DNA. In situ end-labeled neurons demonstrated changes resembling
      apoptosis: nuclear condensation, chromatin fragmentation, and formation of
      apoptotic-like bodies. Ultrastructural analysis confirmed nuclear condensation
      and formation of apoptotic-like bodies. Apoptotic-like changes were seen in the
      substantia nigra of both normal and diseased cases; concomitant
      Alzheimer's/Parkinson's disease and diffuse Lewy body disease cases had
      significantly higher amounts of apoptotic-like changes than normal controls or
      Alzheimer patients. The finding of neuronal death by apoptosis may have relevance
      for the development of new treatment strategies for Parkinson's disease and
      related disorders.

PMID- 9006331
TI  - Detection of the herpesvirus-like DNA sequences in matched specimens of semen and
      blood from patients with AIDS-related Kaposi's sarcoma by polymerase chain
      reaction in situ hybridization.
AB  - The DNA sequences of a novel human gamma-herpesvirus type 8 (HHV-8) have recently
      been detected in Kaposi's sarcoma (KS) lesions obtained from different
      populations in whom this neoplasm occurs, suggesting that this virus may be
      implicated in the etiology and/or pathogenesis of KS. To study the distribution
      and possible means of transmission of the putative viral agent, specimens of KS
      skin lesions, matched uninvolved skin, peripheral blood mononuclear cells (PB
      MCs), and semen were collected from 12 HIV-positive homosexual men with acquired
      immune deficiency syndrome (AIDS)-related KS (AIDS-KS) and 2 human
      immunodeficiency virus (HIV)-negative homosexual men with KS. HHV-8 virus DNA was
      detected by polymerase chain reaction (PCR) studies in all 14 of these KS
      specimens and in 6 of 14 biopsies of normal-appearing skin distant from any KS
      lesions including 1 uninvolved skin specimen from an HIV-negative homosexual male
      with KS. In addition, 3 of 12 PBMC samples and 3 of 12 semen samples from the
      AIDS-KS patients were positive for HHV-8. The DNA sequences of HHV-8 were not
      detected in the matched semen and PBMC specimens obtained from 2 HIV-negative
      homosexual men with KS, 4 HIV-positive homosexual patients without KS, 2 HIV
      seronegative healthy homosexual men, 5 HIV-positive heterosexual male intravenous
      drug users, or 5 healthy HIV-negative heterosexual donors. Using PCR in situ,
      positive signals for HHV-8 were demonstrated in the B lymphocyte subsets of PBMCs
      and/or in spermatozoa and mononuclear cells in the semen from some of the PCR
      positive specimens from the AIDS-KS patients examined. These data show that HHV-8
      is present in and could possibly be transmitted via semen and/or blood from some
      homosexual men with AIDS-KS.

PMID- 9006330
TI  - Prognostic significance of the proliferative activity in neuroblastoma.
AB  - The prognostic significance of the immunohistochemically assessed growth fraction
      in neuroblastomas was determined in relation to tumor grade and tumor stage. A
      total of 101 cases of neuroblastoma were examined with the monoclonal antibodies
      PC10 against proliferating cell nuclear antigen (PCNA) and Ki-S5 against the Ki
      67 protein. Patients were followed for a mean time of 4.8 years. Expression of
      both PC10 and Ki-S5 was found to be significantly linked to tumor grade and tumor
      stage. Prognostically favorable stage IVs was associated with low PCNA and Ki-S5
      levels. For ganglioneuroblastoma, significant differences were found between the
      diffuse and the composite type. In univariate analysis of stage III and IV
      tumors, Ki-S5 and PCNA scores were significantly correlated with disease-free
      survival (P < 0.0015), allowing definition of a subset of cases with favorable
      outcome. As to Shimada's group with poor prognosis, significant differences in
      the clinical course were found for low and high Ki-S5 scores (P = 0.036) but not
      for PCNA. In multivariate analysis, only patient age, Shimada's grade, and Ki-S5
      scores achieved prognostic significance. We conclude that proliferation marker Ki
      S5 may provide substantial prognostic information and might become a useful
      adjunct for predicting the clinical courses of neuroblastoma.

PMID- 9006332
TI  - BCL-6 protein expression in AIDS-related non-Hodgkin's lymphomas: inverse
      relationship with Epstein-Barr virus-encoded latent membrane protein-1
      expression.
AB  - This study aimed at investigating the expression of the BCL-6 protein in acquired
      immune deficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS-NHLs) and
      at comparing the expression pattern with the presence of Epstein-Barr virus (EBV)
      infection of the tumor clone. A total of 34 AIDS-NHL biopsies, including 16 AIDS
      related diffuse large-cell lymphomas (AIDS-DLCLs) and 18 AIDS-related small
      noncleaved-cell lymphomas (AIDS-SNCCLs) as well as 7 AIDS-SNCCL cell lines were
      immunostained with a BCL-6-specific monoclonal antibody. Expression of BCL-6
      protein was detected in 9 of 16 AIDS-DLCLs, 18 of 18 AIDS-SNCCLs, and 3 of 7 AIDS
      SNCCL cell lines. Expression of BCL-6 among AIDS-NHLs occurred independently of
      the presence of molecular lesions of the bcl-6 gene. Notably, among EBV-positive
      AIDS-NHL biopsies and cell lines, expression of BCL-6 was mutually exclusive with
      the expression of EBV-encoded transforming antigen latent membrane protein-1. The
      mutual exclusion between BCL-6 and latent membrane protein-1 expression was
      further confirmed by in vitro superinfection experiments of an AIDS-SNCCL cell
      line originally devoid of EBV sequences. Overall, the frequent association
      between AIDS-NHLs and expression of BCL-6, a protein selectively expressed by
      germinal center B cells, suggests that these lymphomas may originate from the
      germinal center.

PMID- 9006333
TI  - WAF1/Cip1 gene polymorphism and expression in carcinomas of the breast, ovary,
      and endometrium.
AB  - The p53 gene is altered in approximately 50% of human cancers and is considered
      to be important in the pathogenesis of these malignancies. The p53 protein
      product regulates the transition from G1 to S phase of the cell cycle and entry
      to the DNA damage repair pathway. As alterations in this pathway appear to be
      important in a variety of human cancers, downstream effector proteins of p53 are
      potential sites for somatic alterations. WAF1/Cip1, also known as WAF1, Cip1,
      sdi1, or CAP20, codes for a 21-kd protein (p21WAF1/Cip1), which was recently
      described as a universal inhibitor of cyclins and is thus critical in cell cycle
      control. Mutations in WAF1/Cip1 are potentially important in human malignancies
      because they could affect the control of the cell cycle. To understand whether
      mutations of WAF1/Cip1 occur in cancer, we screened 53 cases of invasive breast
      carcinoma, 35 cases of ductal carcinoma in situ (DCIS), 53 ovarian carcinomas,
      and 47 endometrial carcinomas in the second exon of WAF1/Cip1 (90% of the open
      reading frame). p21WAF1/Cip1 expression was characterized with
      immunohistochemistry. Cells from the blood of 21 normal individuals were also
      characterized using single-strand conformational polymorphism analysis, DNA
      sequencing and restriction analysis. Single-strand conformational polymorphism
      analysis demonstrated an altered mobility pattern for exon 2 in 12 invasive
      breast cancers (22.6%), 5 DCIS of the breast (14%), 8 invasive ovarian carcinomas
      (15%), and 9 endometrial carcinomas (19%). In total, 209 samples were screened,
      and 38 cases (18.2%) had an altered codon 31. Each case with altered single
      strand conformational polymorphism, analyzed by DNA sequencing and/or restriction
      analysis, showed the same alteration of codon 31, a C to A transversion encoding
      a change in amino acid sequence from serine to arginine (31Ser-->31Arg). DNA from
      the blood of 21 normal individuals showed the same alteration in WAF1/Cip1 in 4
      cases (19%). Furthermore, paired normal tissue was available for 3 of 20 breast
      carcinomas with the Ser31Arg transversion. Normal DNA from all 3 cases showed the
      same 31Arg alteration as found in the tumor tissue. These results indicate that
      codon 31 is a polymorphic site and that the serine to arginine shift is a
      polymorphism. p21WAF1/Cip1 expression, identified by immunohistochemistry, was
      found to vary in a pattern that depended both on the tissue type and on the
      presence or absence of the codon 31 polymorphism. Using pair-wise comparisons in
      breast DCIS, we found higher protein expression in tumor nuclei as compared with
      benign stromal cell nuclei (P = 0.002) or normal ductal epithelium (P = 0.005).
      Invasive breast cancer specimens showed a trend in p21WAF1/Cip1 immunostaining
      similar to DCIS but did not reach statistical significance (P = 0.12). However,
      when cases with extensive desmoplastic reaction were excluded, a statistically
      significant association (P = 0.019) similar to that in DCIS was noted. In
      contrast to the breast tumors, ovarian carcinomas exhibited significantly greater
      p21WAF1/Cip1 expression in the benign stromal (fibroblast) nuclei surrounding the
      tumor than in the carcinoma cell nuclei (P = 0.016). Endometrial carcinoma
      revealed no difference in staining when comparing benign tissue with carcinoma (P
      = 0.99); however, unlike breast and ovarian carcinomas in which there was no
      correlation between p21WAF1/Cip1 expression and the presence or absence of the
      alteration at the 31st codon, endometrial carcinomas showed an increased
      percentage of immunopositive nuclei associated (P = 0.056) with 31Arg. These
      results demonstrate tissue-specific expression patterns of WAF1/Cip1 in different
      tumors which appears to be characteristic of the tumor type.

PMID- 9006334
TI  - p53 gene mutations are common in uterine serous carcinoma and occur early in
      their pathogenesis.
AB  - Uterine serous carcinoma (USC) is an uncommon but aggressive type of endometrial
      cancer associated with rapid progression of disease and a poor prognosis. Both
      USC and its recently described putative precursor, endometrial intraepithelial
      carcinoma (EIC), demonstrate strong p53 overexpression by immunohistochemistry,
      suggesting alteration of the p53 gene in their pathogenesis. In the present
      study, we evaluated 21 USCs and 9 EICs for mutations in the p53 gene using direct
      sequence analysis and found that 90% of USCs and 78% of EICs contain mutations.
      Significantly, mutations were found in 3 cases of EIC without associated invasive
      carcinoma and identical mutations were detected in cases with synchronous USC and
      EIC. Strong p53 immunoreactivity was seen in the majority of USCs and EICs and
      correlated with p53 gene mutation, although lack of reactivity did not always
      indicate the absence of a gene mutation. Loss of heterozygosity of chromosome 17p
      was observed in 100% of USCs and in 43% of EICs, demonstrating that loss of the
      wild-type p53 allele occurs early in the development of serous carcinoma.
      Overall, our results reveal that p53 mutations are very common in USC and EIC.
      The presence of p53 gene mutations in EIC further suggests that p53 alteration
      plays an important role early in the pathogenesis of serous carcinoma, possibly
      accounting for its aggressive biological behavior.

PMID- 9006335
TI  - Topographic distribution of homing receptors on B and T cells in human gut
      associated lymphoid tissue: relation of L-selectin and integrin alpha 4 beta 7 to
      naive and memory phenotypes.
AB  - In mice, integrin alpha 4 beta 7 is the main receptor used by lymphocytes that
      home to the Peyer's patches, although L-selectin contributes to the initial
      interaction with high endothelial venules. Less is known about the expression and
      function of these adhesion molecules in humans. The distribution of L-selectin
      and alpha 4 beta 7 on various B- and T-cell subsets was examined in human Peyer's
      patches (n = 8) and appendix (n = 4), collectively called gut-associated lymphoid
      tissue. Multicolor immunophenotyping was performed on cryosections, and dispersed
      cells were examined by flow cytometry. In cryosections, CD45RA+ T cells around
      and within interfollicular high endothelial venules, as well as surface (s)IgD+ B
      lymphocytes in the follicle mantles, often expressed abundant L-selectin but only
      intermediate levels of alpha 4 beta 7. CD45RO+ T cells and sIgD- B cells
      expressed higher levels of alpha 4 beta 7 and were often located near putative
      efferent lymphatics; only a small fraction (< 20%) of such memory cells expressed
      L-selectin. By flow cytometry, considerably more T than B lymphocytes co
      expressed L-selectin and alpha 4 beta 7 (40% versus 25% and 67% versus 39%,
      respectively). In samples with many L-selectin+ cells (> 30%), more of these
      lymphocytes co-expressed alpha 4 beta 7 than in samples with few L-selectin+
      cells. Because L-selectin and alpha 4 beta 7 were co-expressed on lymphocytes
      located near high endothelial venules, and because such co-expression was
      relatively common when many L-selectin+ cells were present, both of these
      molecules might participate in homing to human gut-associated lymphoid tissue.
      Such homing is probably most pronounced for T lymphocytes that were found to
      express L-selectin and alpha 4 beta 7 more often than B lymphocytes. The
      selective and relatively high expression of alpha 4 beta 7 on memory cells
      located near efferent lymphatics indicated a different migratory capacity; after
      exit from gut-associated lymphoid tissue, such stimulated cells might home mainly
      to mucosal effector sites.

PMID- 9006336
TI  - Elevated expression of fatty acid synthase and fatty acid synthetic activity in
      colorectal neoplasia.
AB  - Expression of the primary enzyme catalyzing the synthesis of fatty acids, ie,
      fatty acid synthase (FAS), and ex vivo fatty acid synthetic activity were
      examined in colorectal epithelium and neoplasms, including the relationship to
      tumor progression and prognosis. Immunohistochemistry for FAS showed only faint
      staining of native colorectal mucosa, but increased expression was found in all
      sporadic adenomas (n = 18), adenomas associated with familial adenomatous
      polyposis (n = 7), hyperplastic polyps (n = 3), dysplasias arising in ulcerative
      colitis (n = 17), and colorectal carcinomas (n = 130) including 11 with
      contiguous adenomas. The intensity of staining was strong in 53% of carcinomas,
      intermediate in 38%, and weak in 9%. Activity of the fatty acid synthetic pathway
      measured by labeling of six surgical specimens with [U-14C]acetate was 2- to 7
      fold higher in colorectal carcinomas than adjacent native mucosa (P = 0.006) and
      6- to 16-fold higher than serosal fat (P = 0.01). Activity correlated with
      immunohistochemical expression (Spearman's rank correlation coefficient = 0.85; P
      < 0.001). There was no statistically significant association between patient
      survival and FAS staining intensity of carcinomas. Our study shows that FAS is
      expressed in all colorectal neoplasms and there is a concomitant increase in
      fatty acid synthesis. FAS may therefore represent a potential therapeutic target.

PMID- 9006337
TI  - Type I (RI) and type II (RII) receptors for transforming growth factor-beta
      isoforms are expressed subsequent to transforming growth factor-beta ligands
      during excisional wound repair.
AB  - Transforming growth factor (TGF)-beta isoforms (TGF-beta 1, -beta 2, and -beta 3)
      regulate cell growth and differentiation and have critical regulatory roles in
      the process of tissue repair and remodeling. Signal transduction for TGF-beta
      function is transmitted by a heteromeric complex of receptors consisting of two
      serine/threonine kinase transmembrane proteins (RI and RII). We have previously
      shown that each TGF-beta isoform is widely expressed in a distinct spatial and
      temporal pattern throughout the processes of excisional and incisional wound
      repair. As the presence of TGF-beta receptors determines cellular responsiveness,
      we have currently examined, by immunohistochemistry, the localization of RI (ALK
      1, ALK-5) and RII throughout repair of full-thickness excisional wounds up to 21
      days after wounding. The expression of RI (ALK-5) and RII co-localized in both
      the unwounded and wounded skin and was present in the same cell types as TGF-beta
      ligands. However, immunoreactivity for TGF-beta receptors, throughout repair,
      occurred 1 to 5 days later than TGF-beta isoform immunostaining. This implies
      that the presence of TGF-beta ligands may up-regulate TGF-beta receptors for
      function and/or may reflect a lag due to local processing of latent TGF-beta. As
      observed for the immunohistochemical localization of TGF-beta isoforms in
      unwounded skin, RI and RII were expressed throughout the four layers of the
      epidermis, showing a wavy pattern of slight to moderate immunostaining, and hair
      follicles, sweat glands, and sebaceous glands were moderately immunoreactive. The
      extracellular matrix, fibroblasts, and blood vessels in the dermis were not
      immunoreactive. After injury, as observed for TGF-beta ligands, RI and RII
      expression was increased in the epidermis adjacent to the wound and the
      epithelium migrating over the wound was completely devoid of TGF-beta receptor
      immunoreactivity until re-epithelialization was completed by day 7 after
      wounding. The dermis was only slightly immunoreactive for RI and RII until day 5
      when, immediately under the wound, immunostaining for fibroblasts, connective
      tissue cells, and newly forming vasculature began to increase and remained
      intense until day 14. Consistent with the role for TGF-beta in scarring, numerous
      fibroblasts, ostensibly active in the production of extracellular matrix
      components, continued to be slightly immunoreactive for RI and RII at 21 days.
      The ALK-1 (TSR-1) type I receptor, which binds both activin and TGF-beta, showed
      slight immunostaining early in repair (days 1 to 7) that progressively became
      more intense later in repair after day 10 and through day 21. This suggests that
      there may be a switch to a different type I receptor, implying different
      functions for the ALK-1 and ALK-5 receptors. The concomitant expression of TGF
      beta isoforms and their signal-transducing receptors denote potential spatial and
      temporal activity of TGF-beta. Thus, although TGF-beta ligand is present, TGF
      beta would not function in wound repair until a later time when RI and RII
      appear. This information should aid in the development of receptor antagonists as
      a therapeutic approach to scarring and fibrosis. In addition, these studies
      underscore the importance of defining the expression of proteins in vivo to
      establish a basis for the analysis of mechanisms in vitro.

PMID- 9006338
TI  - Neutrophil fate in experimental glomerular capillary injury in the rat.
      Emigration exceeds in situ clearance by apoptosis.
AB  - Neutrophils (PMNs) and their toxic contents can injure glomeruli, but to date
      their fate in glomerulonephritis has been unknown. We studied glomerulonephritis
      induced in rats by formation of concanavalin A (Con A)/anti-Con A immune
      complexes on glomerular endothelial cells. PMN infiltration, which was almost
      exclusively confined to the lumen of glomerular capillaries, was transient,
      peaking at 4 hours, with only 9.0 +/- 4.1% (mean +/- SEM) of the maximum
      remaining at 24 hours. There was clear evidence of PMN apoptosis leading to
      phagocytosis in situ by intraluminal macrophages. However, the kinetics of
      leukocyte infiltration and PMN apoptosis, the preferential location at 24 hours
      of apoptotic PMNs within occluded capillary loops, and tracking of radiolabeled
      PMNs all indicated that in situ phagocytic clearance after apoptosis was the fate
      of a minority of PMNs, amounting to no more than one-fifth of the peak
      infiltrating load. Instead, the majority of infiltrating PMNs (72.9 +/- 3.1%) had
      emigrated from inflamed glomeruli by 24 hours, apparently returning to the
      circulation. We conclude that PMN emigration from inflamed glomeruli is a
      hitherto unrecognized mechanism for regulation of PMN-mediated glomerular injury.

PMID- 9006339
TI  - Migration inhibitory factor expression in experimentally induced endotoxemia.
AB  - Macrophage migration inhibitory factor (MIF) is an important constituent of the
      host response to stress and infection and is the first mediator that has been
      identified to be released from immune cells upon stimulation with
      glucocorticoids. MIF also has been shown to be secreted from the anterior
      pituitary gland, monocytes/macrophages, and T cells activated by various
      proinflammatory stimuli. Once released, MIF acts to counter-regulate the
      inhibitory effect of glucocorticoids on inflammatory cytokine production. To
      characterize more precisely the role of MIF in the host response to infection, we
      undertook a systematic analysis of MIF expression in various organs of the rat
      after endotoxin (lipopolysaccharide) administration. MIF protein and mRNA were
      analyzed by immunohistochemistry and in situ hybridization, respectively. MIF was
      found to be expressed constitutively in organs such as the lung, liver, kidney,
      spleen, adrenal gland, and skin. Significant quantities of MIF protein were
      detected preformed in various cell types and appeared to be released as a
      consequence of endotoxemia. In virtually all tissues examined, the loss of MIF
      protein 6 hours after lipopolysaccharide administration was accompanied by the
      induction of MIF mRNA and, at 24 hours, by the restoration of immunoreactive,
      intracellular MIF. The constitutive production of MIF by several cell and tissue
      types together with its rapid release from intracellular pools distinguishes MIF
      from other cytokines or hormonal mediators and significantly expands the
      physiological role of this unique counter-regulator of glucocorticoid action.

PMID- 9006340
TI  - Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced
      hemorrhagic cystitis.
AB  - The involvement of nitric oxide (NO) and the potential modulation of NO synthase
      (NOS) activity by platelet-activating factor were investigated in a rat model of
      cyclophosphamide-induced hemorrhagic cystitis. Male Wistar rats received a single
      intraperitoneal injection of cyclophosphamide, and cystitis was evaluated 6, 12,
      24, 48, and 72 hours later by determining the changes in bladder wet weight and
      plasma protein extravasation and the macro- and microscopic morphological
      alterations. In addition, NOS activity and NADPH-diaphorase histochemistry were
      studied in bladder tissues. Normal bladders showed extensive NADPH-diaphorase
      staining and a high level of constitutive NOS whereas the activity of inducible
      NOS was almost undetectable. Cyclophosphamide dose- and time-dependently
      increased the bladder wet weight and bladder plasma protein extravasation. These
      events were accompanied at a microscopic level by urothelial necrosis, sloughing,
      ulceration, hemorrhage, and leukocyte infiltration. Cyclophosphamide also
      increased the levels of inducible NOS but reduced those of constitutive NOS. The
      NOS inhibitors L-NG-nitroarginine methyl ester and L-NG-nitroarginine
      significantly reduced the cyclophosphamide-induced plasma protein extravasation
      and urothelial damage. This reduction was completely reversed by L-arginine but
      not by D-arginine. The administration of the platelet-activating factor
      antagonist BN 52021 decreased the cyclophosphamide-induced plasma protein
      extravasation as well as the rise in inducible NOS activity but had no effect on
      the fall in constitutive NOS activity. These results suggest that endogenous NO
      participates in the urothelial damage and in the inflammatory events leading to
      cyclophosphamide-induced hemorrhagic cystitis. Platelet-activating factor also
      seems to be involved in the pathogenesis of this condition, possibly by inducing
      NOS.

PMID- 9006341
TI  - Resistance to cerebral malaria in tumor necrosis factor-alpha/beta-deficient mice
      is associated with a reduction of intercellular adhesion molecule-1 up-regulation
      and T helper type 1 response.
AB  - Tumor necrosis factor (TNF) induced by Plasmodium berghei ANKA (PbA) infection
      was suggested to play an important role in the development of cerebral malaria
      (CM). We asked whether TNF-alpha/beta double-deficient mice, which have a
      complete disruption of the TNF-signaling pathways, are protected from CM and what
      might be the possible mechanisms of protection. PbA infection induces fatal CM in
      wild-type mice, which die within 5 to 8 days with severe neurological signs. In
      contrast, TNF-alpha/beta-deficient mice are completely resistant to PbA-induced
      CM. As PbA-induced up-regulation of endothelial intercellular adhesion molecule
      (ICAM)-1 expression as well as the systemic release of nitric oxide is found only
      in wild-type mice, TNF is apparently central for the recruitment of mononuclear
      cells and microvascular damage. Mononuclear cell adhesion to the endothelium,
      vascular leak and, perivascular hemorrhage are found only in the brain of wild
      type mice. By contrast, the development of parasitemia and anemia is independent
      of TNF. Resistance to CM in TNF-alpha/beta-deficient mice is associated with
      reduced interferon-gamma and interleukin-12 expression in the brain, in the
      absence of increased T helper type 2 cytokines. In conclusion, TNF apparently is
      required for PbA-induced endothelial ICAM-1 up-regulation and subsequent
      microvascular pathology resulting in fatal CM. In the absence of TNF, ICAM-1 and
      nitric oxide up-regulation are reduced, and PbA infection fails to cause fatal
      CM.

PMID- 9006342
TI  - Restricted expression of cell adhesion kinase-beta in rat tissues.
AB  - Cell adhesion kinase-beta (CAK-beta) is a protein tyrosine kinase of the focal
      adhesion kinase subfamily, which contains large amino- and carboxyl-terminal
      domains. We studied the tissue distribution of CAK-beta and its mRNA by
      immunohistochemical staining and in situ hybridization. In rat brain, CAK-beta
      was mainly found in the medulla whereas CAK-beta mRNA was expressed in most
      neurons, especially pyramidal cells and Purkinje cells. In the small intestine,
      CAK-beta protein and mRNA were detected in the absorptive epithelial cells, and
      the protein was concentrated in the brush border. Double immunostaining for CAK
      beta and actin showed that they co-localized in the brush border of small
      intestine cells. Immunoelectron micrography revealed that the anti-CAK-beta
      antibody localized within microvilli. In the kidney, the protein was mainly
      expressed in proximal tubular cells, which have well developed microvilli,
      although CAK-beta mRNA was observed in most urinary tubular cells. In other
      tissues, the ciliated cells of the epididymis strongly expressed CAK-beta mRNA
      and CAK-beta localized in the cilia. In addition, alpha- and beta-tubulin were
      identified in the rat brain lysates immunoprecipitated with anti-CAK-beta
      antibody. The present results demonstrate that CAK-beta is present at relatively
      high levels in cilia, axons, and microvilli. This suggests that CAK-beta may play
      important roles in the functions of these structures or that the CAK-beta-related
      signaling pathway is closely associated with cytoskeletal components.

PMID- 9006343
TI  - In situ stromal expression of the urokinase/plasmin system correlates with
      epithelial dysplasia in colorectal adenomas.
AB  - An increase of urokinase-type plasminogen activator (uPA) and a decrease of
      tissue-type PA (tPA) have been associated with the transition from normal to
      adenomatous colorectal mucosa. Serial sections from 25 adenomas were used to
      identify PA-related caseinolytic activities by in situ zymography, blocking
      selectively uPA or tPA. The distribution of uPA, tPA, and type 1 PA inhibitor
      mRNAs was investigated by nonradioactive in situ hybridization, and the receptor
      for uPA was detected by immunostaining. Low- and high-grade epithelial cell
      dysplasia was mapped histologically. Results show that 23 of 25 adenomas
      expressed uPA-related lytic activity located predominantly in the periphery
      whereas tPA-related activity was mainly in central areas of adenomas. In 15 of 25
      adenomas, uPA mRNA was expressed in stromal cells clustered in foci that
      coincided with areas of uPA lytic activity. The probability of finding uPA mRNA
      reactive cells was significantly higher in areas with high-grade epithelial
      dysplasia. uPA receptor was mainly stromal and expressed at the periphery. Type 1
      PA inhibitor mRNA cellular expression was diffuse in the stroma, in endothelial
      cells, and in a subpopulation of alpha-smooth muscle cell actin-reactive cells.
      These results show that a stromal up-regulation of the uPA/plasmin system is
      associated with foci of severe dysplasia in a subset of colorectal adenomas.

PMID- 9006345
TI  - Different patterns of DNA alterations detected by restriction landmark genomic
      scanning in heterogeneous prostate carcinomas.
AB  - Alterations in the genomic DNAs of six heterogeneous prostate carcinomas, as well
      as that of individual and histologically distinct foci within the tumors, were
      examined using restriction landmark genomic scanning, a method employing two
      dimensional gel analysis of a large number of DNA fragments generated by
      digestion with highly specific endonucleases. Upon autoradiographic imaging,
      these fragments appear as spots of varying intensity and location specific for
      each sample. In our study, comparison of cancer DNAs against normal prostate DNA
      controls yielded alterations in at least 35 spots. Despite differences in the
      histological grading of tumors, 3 spots common to all tumor samples showed
      consistent amplification of intensity and 8 other common spots demonstrated
      consistent reduction of intensity when compared with control. In addition, spot
      alterations occurred between histologically identical foci isolated from within
      single tumors. We suggest that these spot changes detected in DNA profiles
      generated by restriction landmark genomic scanning reflect aberrations in as yet
      unidentified oncogenes and tumor suppressor genes and indicate that prostate
      cancer is not only histologically heterogeneous and multifocal but also
      genetically multicentric.

PMID- 9006344
TI  - Analysis of loss of heterozygosity on chromosome 11q13 in atypical ductal
      hyperplasia and in situ carcinoma of the breast.
AB  - Identical allelic loss in invasive and adjacent in situ ductal breast carcinoma
      (DCIS) on chromosome 11q13 has been previously reported, providing molecular
      evidence for the progression of DCIS to invasive tumor. In this study we analyzed
      loss of heterozygosity (LOH) on 11q13 (PYGM, INT-2) in atypical ductal
      hyperplasia (ADH) and various histological types of in situ carcinomas of the
      breast in patients without invasive cancer. Twenty-four cases of in situ
      carcinoma and twelve cases of ADH were studied. Tissue microdissection of normal,
      hyperplastic, and tumor cells from fixed, paraffin-embedded sections was
      performed, and DNA was extracted for polymerase chain reaction. In situ tumors
      included both high- and low-grade DCIS. LOH was identified in six of twenty-two
      (27.3%) in situ tumors and in one of eleven (9%) ADH cases. Within in situ
      carcinomas, LOH was identified in six of seventeen (35%) high-grade DCIS but in
      none of six low-grade DCIS. The present results show that LOH at 11q13 occurs in
      an appreciable proportion of high-grade DCIS, although the rate is substantially
      less than in patients with concomitant DCIS and invasive tumor. LOH was
      identified less frequently in low-grade in situ tumors and ADH, suggesting that a
      putative tumor suppressor gene(s) located on chromosome 11q13 may be involved in
      the transition from early preneoplastic lesions to invasive breast cancer.

PMID- 9006346
TI  - Monoclonal origin of vulvar intraepithelial neoplasia and some vulvar
      hyperplasias.
AB  - Squamous neoplasms of the female genital tract, including vulvar intraepithelial
      neoplasia, presumably are derived from a single cell. This study addressed this
      hypothesis and determined the clonal status of other squamous epithelial
      alterations associated with vulvar carcinoma, including hyperplasia and lichen
      sclerosis. X chromosome inactivation patterns of 22 epithelial lesions and
      matched normal epithelium were determined using a polymerase chain reaction (PCR)
      based assay targeting the X-linked human androgen receptor gene (HUMARA).
      Clonality was inferred by comparing matched lesional and control tissues as
      follows: 1) monoclonal, if intensity of either PCR product was skewed relative to
      normal reference epithelium (control), 2) polyclonal, if both lesional and
      control were unskewed, and 3) unknown, if both lesion and control tissues were
      skewed toward the same allele. Two cases were excluded because of noninformative
      homozygous HUMARA alleles. Of 8 vulvar intraepithelial neoplasias analyzed, 7
      were scored monoclonal and 1 polyclonal. Of 12 hyperplasias, 6 were monoclonal,
      including one with lichen sclerosis, 2 were polyclonal, and in 4, the clonal
      status could not be determined. The PCR-based clonal assay supports a monoclonal
      derivation for vulvar intraepithelial neoplasia and, in some cases, vulvar
      hyperplasia, and lichen sclerosis. The finding of monoclonal hyperplasia and
      lichen sclerosis suggests that clonal expansion may evolve before the development
      of morphological atypia in these epithelia.

PMID- 9006347
TI  - Tissue inhibitor of metalloproteinases-3 is a component of Bruch's membrane of
      the eye.
AB  - Mutations in tissue inhibitor of metalloproteinases (TIMP)-3 are found in some
      patients with Sorsby's fundus dystrophy, a retinal degeneration characterized by
      abnormal deposits in Bruch's membrane and choroidal neovascularization. The
      purpose of this study was to localize TIMP-3 in the retina/choroid of normal
      human and animal eyes. Immunolabeling was performed on unfixed and fixed sections
      of human eyes aged 24 to 85 years and unfixed sections of baboon, chicken, cow,
      pig, and rat eyes using a monoclonal antibody against a human TIMP-3 synthetic
      peptide. The antibody produced strong immunolabeling of Bruch's membrane and
      drusen and weak labeling of retina blood vessels in unfixed human and baboon
      eyes. Unfixed chicken, cow, pig, and rat tissues showed no reactivity. After
      antigen retrieval, all fixed human eyes showed specific labeling of Bruch's
      membrane and drusen, which was strongest in eyes from elderly donors. The results
      indicate that TIMP-3 is an extracellular matrix component of Bruch's membrane.
      Thus, abnormal local function of TIMP-3 may lead to the characteristic Bruch's
      membrane deposits and choroidal neovascularization found in Sorsby's fundus
      dystrophy. Specific labeling of drusen raises the possibility that altered TIMP-3
      mediated matrix remodeling may contribute to age-related degenerative changes in
      Bruch's membrane.

PMID- 9006349
TI  - Acetylcholine receptor alpha-subunit isoforms are differentially expressed in
      thymuses from myasthenic patients.
AB  - A central role of the thymus in autosensitization to the acetylcholine receptor
      has been proposed to explain the immunopathogenetic processes in myasthenia
      gravis (MG). Two isoforms of the alpha-subunit of the acetylcholine receptor are
      known; they differ by a 25-amino-acid insertion coded by the P3A exon. We
      investigated the expression of the P3A exon by RNA polymerase chain reaction in
      fetal and adult human myoblasts and TE671 cells; both isoforms were expressed.
      Muscle biopsies from patients with MG, Duchenne muscular dystrophy, and
      polymyositis were also studied and it was again found that both isoforms were
      expressed, indicating that the P3A exon is not associated with autoimmune,
      degenerative, and inflammatory muscle diseases. When P3A expression was studied
      in thymus samples from normal subjects and from thymectomized MG patients, the
      P3A+ subunit was absent in 75% of patients with involuted thymus and in all
      patients with thymomas but was present in normal thymuses and in patients with
      hyperplasia. Differential expression of the alpha-subunit isoforms of the
      acetylcholine receptor within the thymus may play a role in the immune
      pathogenesis of MG.

PMID- 9006348
TI  - Interleukin-1 beta-induced disruption of the retinal vascular barrier of the
      central nervous system is mediated through leukocyte recruitment and histamine.
AB  - The vascular barriers of the central nervous system form a selective cellular
      interface between the blood and the neural parenchyma and restrict the transfer
      of both molecules and hematogenous cells. During immune-mediated diseases,
      leukocyte infiltration becomes dramatically up-regulated and the permeability of
      these barriers increases, leading to edema formation. The etiology of this damage
      remains largely unresolved although inflammatory cytokines have been implicated
      in the process. The effect of the proinflammatory cytokine interleukin (IL)-1
      beta on the integrity of the rat blood-retinal barrier (BRB) was investigated up
      to 14 days after an intravitreal injection. The permeability of the BRB was
      evaluated quantitatively using the low molecular weight tracer [14C]mannitol.
      After IL-1 beta administration, a biphasic opening of the BRB to [14C]mannitol
      was recorded, peaking at 4 to 8 hours and 24 to 48 hours post-injection (PI). The
      early disruption coincided with the appearance of both polymorphonuclear and
      mononuclear leukocytes within the retina. By 12 hours PI, BRB permeability had
      returned to control values despite a continued increase in the number of
      infiltrating leukocytes. The second, more pronounced increase in barrier
      permeability detected at 24 to 48 hours PI corresponded with maximal leukocyte
      infiltration. Barrier dysfunction had resolved by 72 hours, and by 7 days the
      leukocyte infiltrate had disappeared. The IL-1 beta-induced increase in
      permeability could be completely abrogated at 4 and 24 hours PI by treating the
      animals with the histamine H2-receptor antagonist ranitidine, which also reduced
      leukocyte infiltration by 47.2%. The ability of histamine to disrupt the BRB was
      demonstrated by intravitreal and intravascular administration, which caused a
      rapid and significant increase in BRB permeability. Treatment of the animals with
      the cyclo-oxygenase inhibitor indomethacin had no effect on IL-1 beta-induced
      disruption of the BRB at 4 hours PI, but by 24 hours PI a significant reduction
      in permeability was observed that coincided with a 75.2% reduction in the
      leukocyte infiltrate. The depletion of circulating leukocytes to < 2% of control
      levels reduced the retinal leukocyte recruitment induced by IL-1 beta by 73.0%
      and decreased BRB permeability at both 4 and 24 hours after IL-1 beta injection.
      These data demonstrate that intravitreal IL-1 beta in the rat induces a biphasic
      opening of the BRB that appears to be mediated through recruited leukocytes and
      release of the vasoactive amine histamine.

PMID- 9006351
TI  - Urokinase-type plasminogen activator-deficient mice are predisposed to
      staphylococcal botryomycosis, pleuritis, and effacement of lymphoid follicles.
AB  - Urokinase-type plasminogen activator (uPA) is thought to be an important mediator
      in the proteolytic degradation of extracellular matrix components observed in a
      wide variety of normal physiological and pathological conditions. However, the
      phenotype of a recently developed strain of urokinase-deficient (uPA-/-) mice
      appears to be normal when maintained under ideal nonstressful conditions. We
      report an outbreak of botryomycosis, an unusual staphylococcal infection, in a
      colony of uPA-deficient mice. A detailed histological examination of these uPA
      deficient animals also revealed a variety of previously unreported phenotypic
      abnormalities such as pleuritis and the effacement of lymphoid follicles in the
      regional lymph nodes and spleen. Additional phenotypic abnormalities such as
      dystrophic calcifications and rectal prolapse were also observed in the uPA
      deficient population. These abnormalities were also noted in ostensibly healthy
      uPA-deficient animals. Botryomycosis did not affect a colony of wild-type
      (uPA+/+) animals maintained concurrently under identical conditions in the same
      room. The peculiar predisposition of the uPA-deficient animals to this rare
      bacterial infection and the development of phenotypic abnormalities associated
      with the targeted disruption the uPA gene suggests that uPA contributes
      significantly to the cutaneous microenvironment and is additional evidence of the
      extensive involvement of the plasminogen activators in mammalian physiology.

PMID- 9006350
TI  - Production of the immunosuppressive cytokine interleukin-10 by Epstein-Barr-virus
      expressing pyothorax-associated lymphoma: possible role in the development of
      overt lymphoma in immunocompetent hosts.
AB  - Malignant lymphomas frequently develop in the pleural cavity of patients with
      long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has
      been proposed for this type of tumor. Most PALs are diffuse lymphomas of B cell
      type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma
      cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell
      lines contain EBV DNA, but only OPL-1 expresses EBV nuclear antigen 2, which
      works as a target molecule for the cell-mediated immune response. As systemic
      immunodeficiency is unlikely to be present in PAL patients, PAL from which OPL-1
      derived was not expected to be fully developed. In this study, we examined the
      expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed
      interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL
      1 and OPL-2 expressed transforming growth factor (TGF)-beta 1 mRNA; however,
      neither expressed latent TGF-beta-binding protein mRNA at a detectable level by
      Northern blot analysis. Because TGF-beta expresses its functions in cooperation
      with latent TGF-beta-binding protein, the biological functions of TGF-beta 1
      could be negligible. Neither cell line expressed at a detectable level EBV BCRF-1
      mRNA, a viral gene product that is partly homologous to human IL-10 and shares
      biological activities of IL-10. Although IL-10 is reported to promote the growth
      of activated or neoplastic B cells, OPL-1 did not respond to human recombinant IL
      10 by growing faster. As OPL-1 expresses a target antigen for the host cytotoxic
      T-cell response, the production of an immuno-suppressive cytokine, IL-10, might
      contribute to the development of overt lymphoma by inducing locally
      immunosuppressive circumstances. The present study suggests that an
      immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent
      patients.

PMID- 9006352
TI  - The presence of apoptotic cells in human atherosclerotic lesions.

PMID- 9006353
TI  - Harold F. Schuknecht 1917-1996.

PMID- 9006354
TI  - Reparative granuloma following stapedectomy: a clinical entity. 1967.

PMID- 9006355
TI  - Treatment of chronic postoperative otorrhea with cultured keratinocyte sheets.
AB  - Cultured allogeneic ear keratinocyte sheets were used to treat 26 ears presenting
      with long-standing (average 37 months) chronic otorrhea, resistant to regular
      treatment, long after surgery for atresia (n = 8), cholesteatoma (n = 10), and
      chronic otitis media (n = 8). Complete epithelial healing and cessation of
      otorrhea were obtained in 18 cases (69%), following an average of 2.2 weekly
      applications. Temporary epithelial healing lasting at least 3 months was observed
      in 3 patients (12%) subsequently needing repeated applications. Lack of complete
      epithelialization was documented in 5 cases (19%). In 3 of those 5 cases, a
      reason could be determined. The authors speculate that the allocultured
      keratinocytes are able to promote migration and proliferation of resident cells
      at the wound edges, despite their short survival time, by release of keratinocyte
      stimulating factors.

PMID- 9006356
TI  - Sudden deafness: a comparison of anticoagulant therapy and carbogen inhalation
      therapy.
AB  - Sudden deafness (SD) is a sudden or rapidly progressive, partial or complete,
      typically unilateral sensorineural hearing impairment that has no known specific
      etiologic factor. This study was designed to compare, in a group of 168
      consecutive patients with SD, the effect of anticoagulant therapy and carbogen
      inhalation therapy. Special attention was paid to the shape of the audiogram
      relative to the clinical outcome and the treatment modality. We found that the
      configuration of the audiogram of SD patients is prognostic of the outcome, and
      that patients with a low-frequency-sloping hearing impairment have a better
      prognosis compared to the patients with a high-sloping loss. Anticoagulant
      treatment was most effective in low-sloping hearing losses, while carbogen
      inhalation may be more effective for patients with high-sloping hearing losses.

PMID- 9006358
TI  - Postnatal change in angle between the tympanic annulus and surrounding
      structures. Computer-aided three-dimensional reconstruction study.
AB  - Postnatal developmental relationships in human ears were studied by a computer
      aided three-dimensional reconstruction and measurement method. We measured the
      angle, in reference to the horizontal plane, between the tympanic annulus, the
      oval window, and the internal auditory canal (IAC) in 20 normal temporal bones
      obtained from individuals between 1 day old and 76 years old. The horizontal
      plane was defined as the plane sloped 30 degrees infero-anteriorly from the plane
      of the horizontal canal in each specimen. The plane of the tympanic annulus
      changed from a nearly horizontal orientation (34.2 degrees from the horizontal
      plane) in neonates to a more vertical orientation (63.3 degrees from the
      horizontal plane) in adults. The tympanic annulus and oval window planes remained
      at the same angle to each other (11.9 degrees +/- 5.1 degrees) throughout
      postnatal development, as did the plane of the tympanic annulus and the IAC (68.6
      degrees +/- 5.3 degrees). These findings have implications for ear surgeons,
      especially those operating on young children.

PMID- 9006357
TI  - Blood flow in common carotid and vertebral arteries in patients with sudden
      deafness.
AB  - Blood flow was measured in the common carotid artery (CCA) and the vertebral
      artery (VA) by the ultrasonic Doppler method in 14 male patients with sudden
      deafness and 70 normal adults. In the patients, blood flow on the affected side
      was slower than that on the normal side or that of the control group. Although
      these differences were not statistically significant in the CCA or in the VA,
      significant differences in the blood flow were noted between the group with a
      hearing loss of greater than 50 dB and the group with a loss of less than 50 dB.
      A negative correlation was found between blood viscosity and blood flow in both
      CCAs and both VAs. After stellate ganglion block (SGB), the blood flow of the CCA
      and VA increased on the side of the SGB and decreased on the opposite side. The
      changes in blood flow after SGB decreased with age, presumably because of changes
      in the blood vessel walls and a weaker response to sympathetic nerve receptors in
      the arterial wall.

PMID- 9006359
TI  - Secretory otitis media in adults: II. The role of mastoid pneumatization as a
      prognostic factor.
AB  - The sequelae of secretory otitis media (SOM) were monitored in 72 adult patients
      with SOM who were followed up for an average of 33 months. It was found that SOM
      became chronic and retraction of the tympanic membrane appeared as a function of
      the pneumatization of the mastoid. Ears with poor pneumatization (less than 6
      cm2) developed chronic SOM in 52.2% of cases, as compared with 20% in cases with
      well-pneumatized ears (6 cm2 and above). Atelectasis developed in 37.3% of poorly
      pneumatized ears, and in only 5.7% of well-pneumatized ears. These sequelae may
      therefore be linked pathogenetically to the extent of pneumatization, as both the
      SOM and the sequelae appeared many years after formation and maturation of the
      pneumatic system. This study supports other studies that view the mastoid
      pneumatic system as an organ, as a middle ear pressure buffer. Well-pneumatized
      ears rarely develop a negative pressure and are seldom associated with chronic
      sequelae. Ears with poorly pneumatized mastoids lack the physiological function
      of such a pressure buffer. Ears with a tendency to develop a negative gas
      balance, whether as a result of deficient ventilation or excessive diffusion,
      will therefore develop a negative pressure more readily when their pneumatic
      system is underdeveloped, and consequently will be more prone to develop chronic
      sequelae.

PMID- 9006360
TI  - Laryngeal adjustment in whispering magnetic resonance imaging study.
AB  - Previous studies confirmed that during whispering the glottis is kept open to
      prevent vocal fold vibration and the supraglottal structures are constricted.
      However, there has been no study exploring the exact contour of the laryngeal
      lumen in the frontal dimension during the production of whispering. In order to
      further elucidate the nature of the laryngeal adjustments regarding the contour
      of the laryngeal lumen in whispering, and the role of supraglottal constriction
      in particular, we conducted a physiological study using magnetic resonance
      imaging. According to the results, the supraglottal structures were not only
      constricted but also shifted downward, attaching to the vocal fold to prevent
      vocal fold vibration completely during whispering. The results suggested the
      underlying mechanism of suppression of vocal fold vibration during the production
      of whispering.

PMID- 9006361
TI  - Age-related changes of elastic fibers in the superficial layer of the lamina
      propria of vocal folds.
AB  - An investigation was carried out to determine the morphologic characteristics of
      elastic fibers in the superficial layer of the lamina propria of aged vocal folds
      (EFAVFs). Excised human adult vocal folds served as the material for this study.
      Scanning and transmission electron microscopic observations were made. The
      results can be summarized as follows. First, the EFAVFs were composed of
      amorphous substances and microfibrils. The amorphous substances increased in
      amount and the microfibrils became less numerous. Second, the EFAVFs ran in
      various directions, were branched, and formed a complicated network. The surface
      of the fibers was rough, and the fibers appeared to vary in size. Some EFAVFs
      united to form a sheet with a rough surface. Third, the EFAVFs could not be
      easily digested by elastase compared with those of younger adults. We conclude
      that the morphologic and metabolic changes of elastic fibers in the most
      important vibrating portion (superficial layer of the lamina propria) of the aged
      vocal folds contribute partially to aging of the voice.

PMID- 9006362
TI  - Mechanics of type IV tympanoplasty: experimental findings and surgical
      implications.
AB  - In a type IV tympanoplasty, the stapes footplate is directly exposed to incoming
      sound while the round window is "shielded," usually with a fascia graft.
      Postoperative hearing results are quite variable, with air-bone gaps ranging from
      10 to 60 dB. A cadaveric human temporal bone preparation was developed to
      investigate the middle ear mechanics of this operation to identify causes of
      variable results and to test predictions of a recently described theoretic model
      of type IV tympanoplasty. The ear canal, tympanic membrane, malleus, and incus
      were removed so as to expose the stapes and round window to the sound stimulus. A
      "cavum minor" chamber (air space adjacent to the round window) was constructed
      around the round window niche. The round window could be isolated from sound by
      placing an acoustic shield over this chamber. The mechanical properties of the
      shield, cavum minor, annular ligament, and round window membrane were varied
      experimentally. Stapes velocity as determined by an optical motion sensor was
      used as a measure of hearing level. The largest stapes velocity occurred with a
      mobile stapes and round window, a stiff shield, and a well-aerated cavum minor.
      Partial fixation of the stapes or round window caused a decrease in stapes
      velocity. Acoustic shields of conchal cartilage or Silastic silicone rubber
      sheeting (approximately 1 mm thick) provided near-optimal shielding. A temporalis
      fascia shield resulted in a stapes velocity 10 to 20 dB less than that seen with
      a cartilage or Silastic silicone rubber shield at low frequencies. A cavum minor
      air space as small as 16 microL was sufficient for unrestricted stapes motion,
      provided the air was in contact with the round window membrane. These results
      qualitatively matched predictions of our model, but there were some quantitative
      differences. The clinical implications of our results are that in order to
      optimize postoperative hearing, the surgeon should 1) preserve normal stapes
      mobility, preferably by covering the footplate with a very thin split-thickness
      skin graft, not a fascia graft; 2) reinforce a fascia shield with cartilage or
      Silastic silicone rubber; 3) create conditions that promote aeration of the round
      window niche; and 4) preserve the mobility of the round window membrane.

PMID- 9006363
TI  - Three-dimensional analysis of spontaneous nystagmus in peripheral vestibular
      lesions.
AB  - The direction of spontaneous nystagmus was recorded in three dimensions with
      scleral dual search coils in three patients after vestibular neurectomy and in
      seven patients with vestibular neuritis. The rotation vectors of the spontaneous
      nystagmus clustered along the sensitivity vector of the lateral semicircular
      canal (SCC). The direction of the spontaneous nystagmus after resection of the
      whole eighth nerve was not different from that after resection of only the
      superior branch of the vestibular nerve. Deviations from this direction were
      observed only after resection of the inferior vestibular nerve and in one patient
      with vestibular neuritis. The absence of nystagmus components in direction of the
      vertical SCC reflects an anisotropy of oculomotor efferents of the vestibulo
      ocular reflex are rather than a lesion limited to the lateral SCC afferents.
      Therefore, the three-dimensional analysis of spontaneous nystagmus does not
      permit accurate localization of a peripheral vestibular lesion.

PMID- 9006365
TI  - Juvenile cemento-ossifying fibroma of the maxilla.

PMID- 9006364
TI  - Immunohistochemical localization of manganese superoxide dismutase in rat
      vestibular dark cell regions.
AB  - A modified immunoglobulin peroxidase bridge sequence method was used to detect
      the localization of manganese superoxide dismutase (MnSOD), a superoxide radical
      (O2-) scavenging enzyme locating in mitochondrial matrix, in the vestibular
      labyrinth of pigmented rats. Strong positive MnSOD immunostaining was
      demonstrated in the dark cell regions of the ampullae, utricle, and common crus.
      The result provides for the first time direct evidence demonstrating the
      existence of mitochondrial O2- scavengers in the vestibular labyrinth and
      illustrates that the specific sites for vestibular MnSOD immunolocalization are
      the dark cell regions. This site specificity of MnSOD immunolocalization suggests
      that dark cell regions may possess high metabolic activity and may encounter
      constant threat from O2-. We assume MnSOD is needed in protecting some
      physiologic functions of the dark cell regions. Cell types showing negative MnSOD
      immunostaining may conceivably be relatively vulnerable to acute O2- damage.

PMID- 9006366
TI  - Clinicopathological consultation. Ear cholesteatoma versus cholesterol granuloma.

PMID- 9006367
TI  - Minocycline treatment for leukocytoclastic vasculitis associated with rheumatoid
      arthritis.

PMID- 9006368
TI  - The homelands of top-cited articles.

PMID- 9006369
TI  - Detection of human herpesvirus 8 and human T-cell lymphotropic virus type 1
      sequences in Kaposi sarcoma.
AB  - BACKGROUND: Ultrastructural studies have shown retroviral particles in Kaposi
      sarcoma (KS) unrelated to infection with the human immunodeficiency virus (HIV).
      Recently, DNA sequences from a new herpesvirus, human herpesvirus 8 (HHV-8), were
      detected in KS tissues. OBJECTIVES: To screen for the presence of HHV-8 sequences
      in patients with KS not related to HIV infection and correlate HHV-8 sequence
      detection and clinical staging and to screen for the presence of human T-cell
      lymphotropic virus type 1 (HTLV-1) sequences in the peripheral blood mononuclear
      cells (PBMCs) of such patients. DESIGN: Tumor and normal skin samples and PBMCs
      were investigated by polymerase chain reaction using primers for HHV-8 and HTLV-1
      pX gag, pol, and env sequences. SETTING: Ambulatory or hospitalized patients from
      a university hospital associated with a research laboratory. PATIENTS: Thirty-one
      patients with KS not related to HIV infection (21 classic cases, 3 endemic cases,
      1 case associated with Castleman disease, 4 homosexual men, 1 post
      transplantation patient, and 1 patient taking corticosteroids). Stages involved
      included I (13 patients), II (8 patients), III (7 patients), and IV (3 patients).
      RESULTS: Human herpesvirus 8 sequences were found in 100% of KS specimens, 70% of
      distant normal skin specimens, and 42% of PBMC samples. The percentage of HHV-8
      detection in PBMCs was higher in patients with KS stage III or IV than in
      patients with stage I or II. Human T-cell lymphotropic virus type I pX sequences
      were detected in 2 of 19 patients while gag, pol, and env test results were
      negative using polymerase chain reaction analysis. CONCLUSIONS: Our data suggest
      no significant association between HTLV-1 infection and KS. Detection of HHV-8
      infected cells in normal skin samples from the majority of KS tissues, regardless
      of clinical staging, can be paralleled to the multifocal pattern of the disease.
      Human herpesvirus 8 detection in PBMCs could be related to the tumor burden.

PMID- 9006370
TI  - Long-term prognosis in patients treated for erythema chronicum migrans and
      acrodermatitis chronica atrophicans.
AB  - OBJECTIVE: To determine whether Lyme borreliosis persisted or had recurred in
      patients treated for erythema chronicum migrans and acrodermatitis chronica
      atrophicans. DESIGN: Retrospective follow-up study. Mean time between treatment
      and follow-up study was 8.8 years (SD, 66.6 years). SETTING: Department of
      dermatology. PATIENTS: Patients (N = 52) treated from July 1964 to October 1992
      for erythema chronicum migrans (ECM; n = 44) or acrodermatitis chronica
      atrophicans (ACA; n = 8). Fifty-two of the 56 successfully contacted and
      registered patients agreed to participate, for a response rate of 93%. MAIN
      OUTCOME MEASURES: Signs and symptoms of Lyme borreliosis; serum antibodies to
      Borrelia burgdorferi. RESULTS: The interval from the time of diagnosis to study
      entry was 0.8 to 28.7 years (mean, 8.2 years). No symptoms or signs of active
      Lyme borreliosis were observed in the 52 patients. Antibodies to B burgdorferi
      were found in the ECM group in 1 of the 23 patients who received a recommended
      treatment and 2 of the 21 patients who received other treatments; antibodies were
      found in the ACA group in all 5 adequately treated patients who received a
      recommended treatment and in 1 of the 3 patients who received other treatments.
      CONCLUSIONS: There was no association between serologic results and type of
      treatment or between serologic results and complaints or symptoms at the time of
      the study in either of the patient groups. The prognosis in most patients with
      Lyme borreliosis is excellent.

PMID- 9006371
TI  - Detection of Borrelia burgdorferi DNA (B garinii or B afzelii) in morphea and
      lichen sclerosus et atrophicus tissues of German and Japanese but not of US
      patients.
AB  - OBJECTIVE: To elucidate the geographic and genospecific association of Borrelia
      with morphea and lichen sclerosus et atrophicus (LSA). DESIGN: The association of
      Borrelia burgdorferi with morphea and LSA has been reported, but is still
      controversial. We conducted a retrospective survey of Borrelia DNA in skin biopsy
      specimens. SETTINGS: The samples were collected from the outpatient clinic of
      university hospitals and a dermatopathology laboratory. PATIENTS: Skin biopsy
      specimens (19 morphea and 34 LSA) were obtained from patients in the United
      States, Japan, and Germany. DNA samples were subjected to amplification with
      polymerase chain reaction for B burgdorferi flagellin gene, and for the genotype
      specific detection of B burgdorferi sensu stricto, Borrelia garinii, and Borrelia
      afzelii. RESULTS: Five cases of morphea and 2 cases of LSA in Germany and Japan
      yielded positive signals for B garinii or B afzelii, the European species. None
      of the American samples were positive for Borrelia polymerase chain reaction.
      Borrelia burgdorferi sensu stricto was not detected in any of the specimens.
      CONCLUSION: Morphea and LSA in Germany and Japan can be related with European
      genotypes of Borrelia.

PMID- 9006372
TI  - Ocular rosacea. Signs, symptoms, and tear studies before and after treatment with
      doxycycline.
AB  - OBJECTIVE: To examine ocular signs, symptoms, and results of tear analysis in
      patients with cutaneous rosacea before, during, and after doxycycline therapy.
      DESIGN: Before-after trial. SETTING: General community. PATIENTS OR OTHER
      PARTICIPANTS: Thirty-nine patients with cutaneous rosacea underwent dermatologic
      and ocular examinations, testing of tear break-up time, and Schirmer testing at
      baseline and 4, 8, and 12 weeks. Six patients did not complete the study.
      Baseline tear break-up time and results of Schirmer test were compared with those
      of 13 patients without rosacea who were matched for age and sex. INTERVENTION:
      Patients with rosacea were given doxycycline, 100 mg daily for 12 weeks. MAIN
      OUTCOME MEASURE: Statistically significant (P, .05) improvement in tear break-up
      time. RESULT: The most frequent ocular symptoms were dryness, itching, blurred
      vision, and photosensitivity, all of which improved significantly with treatment.
      All patients had signs of ocular disease, most commonly erythema and
      telangiectasia, meibomian gland dysfunction, and ciliary base injection.
      Significant improvement (P,.05) for scales, erythema and telangiectasia, ciliary
      base injection, bulbar injection, papillary hypertrophy, and punctate epithelial
      erosions was seen. Average tear break-up time for the patients with rosacea was
      5.7 seconds, which improved to 10.8 seconds after 12 weeks of treatment (P =
      .007). Baseline tear break-up time was significantly lower than for the
      comparison group of normal subjects (P = .001). There was no correlation between
      severity of cutaneous disease and ocular disease. CONCLUSIONS: All patients with
      cutaneous rosacea had some degree of ocular involvement. Tear break-up time is
      abnormal in patients with rosacea. Ocular erythema and telangiectasia, meibomian
      gland dysfunction, and short tear break-up time in patients with cutaneous
      rosacea are indicators of ocular rosacea. Doxycycline, 100 mg daily, will improve
      ocular disease and increase the tear break-up time.

PMID- 9006373
TI  - Hair follicle structures targeted by antibodies in patients with alopecia areata.
AB  - OBJECTIVE: To identify the structures in hair follicles (HFs) targeted by
      alopecia areata (AA) antibodies and the role of antigen expression in the
      development or localization of AA lesions. DESIGN: The identity of HF structures
      targeted by AA antibodies was determined by indirect immunofluorescence and the
      level of antigen expression from the intensity of the staining. SETTING: A
      university medical center. PATIENTS: Ten patients with active AA and 8 control
      individuals. RESULTS: Antibodies to anagen HFs were present in up to 90% of
      patients with AA but in less than 37% of controls. The antibodies in patients
      with AA reacted to antigens present only in HFs. The structures most commonly
      targeted were the outer root sheath and, less often, the inner root sheath,
      matrix, and hair shaft. The same HF structure contained several immunologically
      distinct antigens reactive with AA antibodies. The expression of some AA antigens
      was much greater in the scalp of patients with AA than in normal individuals.
      CONCLUSIONS: These findings indicate that the autoantibody responses to HFs in
      patients with AA are heterogeneous and target multiple structures in anagen HFs.
      The expression of some as-yet-unidentified HF antigens is increased in many
      patients with AA, suggesting that the initiation, localization, severity, and
      persistence of the disease may be related to the level of expression of some HF
      antigens.

PMID- 9006374
TI  - Intralesional fluorouracil/epinephrine injectable gel for treatment of
      condylomata acuminata. A phase 3 clinical study.
AB  - BACKGROUND AND DESIGN: A new intralesional sustained-release chemotherapy is
      under development as a treatment for condylomata acuminata; it is administered as
      an injectable gel that consists of fluorouracil and epinephrine with a purified
      bovine collagen as the gellant (fluorouracil/epinephrine gel). In this
      randomized, double-blind study, we evaluated the safety and efficacy of this
      intralesional treatment in 401 patients, using 2 active drug formulations
      (fluorouracil/epinephrine gel and fluorouracil gel alone) and a placebo. Each
      lesion was injected once a week for up to 6 weeks, and patients were followed up
      for 3 months. RESULTS: A total of 359 patients with 1926 condylomata underwent
      evaluation. For all lesions treated with fluorouracil/epinephrine gel, the
      complete response (CR) rate was 77%. For all patients treated with
      fluorouracil/epinephrine gel, the CR rate was 61%. The fluorouracil/epinephrine
      gel was significantly more effective (P < .002) in treating condylomata than the
      fluorouracil gel without epinephrine (CR rate, 43%); both were superior to
      placebo (CR rate, 5%). At 3 months after completion of treatment, recurrence
      rates in patients with CRs were as follows: fluorouracil/epinephrine gel group,
      50%; fluorouracil gel group, 58%. No clinically significant drug-related systemic
      reactions occurred. Finally, the type and severity of local tissue reactions of
      patients with a positive pretreatment collagen skin test result (6/401 [1.5%])
      were similar to those of patients with a negative collagen skin test result.
      CONCLUSION: The fluorouracil/epinephrine injectable gel is a safe and effective
      treatment for condylomata acuminata.

PMID- 9006375
TI  - Patchy dermal hypoplasia as a characteristic feature of Proteus syndrome.
AB  - BACKGROUND: The diagnostic criteria of Proteus syndrome include various lesions
      of localized overgrowth such as digital gigantism, hemihyperplasia with
      unilateral macrocephaly, epidermal nevus, and mesodermal hamartomas such as
      lipoma, lymphangioma, hemangioma, or fibroma. Hyperplasia of the plantar dermal
      tissue may result in a characteristic cerebriform appearance. However,
      hypoplastic lesions involving various tissues such as subcutaneous fat or muscles
      also may be observed in this syndrome. This paradoxical phenomenon has so far
      been underestimated, and the presence of circumscribed lesions of dermal
      hypoplasia has been entirely ignored. OBSERVATIONS: We report 4 cases of Proteus
      syndrome associated with large patches of dermal hypoplasia, resulting in a more
      prominent appearance of venous vasculature. CONCLUSIONS: Patchy dermal hypoplasia
      appears to be a characteristic feature within the spectrum of Proteus syndrome.
      The anomaly should not be confused with partial lipohypoplasia that may likewise
      be associated with this multisystem birth defect. From a review of the
      literature, we conclude that patchy dermal hypoplasia may have occurred in
      several previous cases. In the future, recognition of this cutaneous anomaly may
      help to establish the diagnosis in otherwise doubtful cases. To explain the
      coexistence of lesions of dermal hyperplasia and hypoplasia, we propose the
      genetic concept of "twin spotting." At the gene locus of Proteus syndrome the
      embryo would carry 1 allele giving rise to dermal overgrowth, whereas the
      corresponding allele would be responsible for a diminished proliferation of
      cutaneous fibroblasts. Somatic recombination may result in 2 different
      populations of cells homozygous for either allele.

PMID- 9006376
TI  - Kaposi sarcoma, Kaposi sarcoma-associated herpesvirus, and human T-cell
      lymphotropic virus type 1. What is the current evidence for causality?

PMID- 9006378
TI  - The truth about erythema migrans.

PMID- 9006377
TI  - Ocular rosacea. Current concepts and therapy.

PMID- 9006379
TI  - A progressive blistering eruption in a patient with lymphoma. Paraneoplastic
      pemphigus.

PMID- 9006380
TI  - Abnormal nails in a patient with severe anemia. Dyskeratosis congenita.

PMID- 9006381
TI  - Periorbital papules and nodules. Necrobiotic xanthogranuloma.

PMID- 9006382
TI  - Solitary facial lesion. Sebaceous adenoma in association with Muir-Torre syndrome
      (MTS).

PMID- 9006383
TI  - Resection margins in primary cutaneous melanoma.

PMID- 9006384
TI  - Revising the practice of melanoma margin resections.

PMID- 9006385
TI  - Additonal observations using a pulsed carbon dioxide laser with a fixed pulse
      duration.

PMID- 9006386
TI  - Kaposi sarcoma unrelated to human immunodeficiency virus infection: long-term
      results of radiotherapy.

PMID- 9006387
TI  - Absence of human herpesvirus 8 DNA sequences in patients with immunosuppression
      associated dermatofibromas.

PMID- 9006388
TI  - Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 and Epstein-Barr
      virus in iatrogenic Kaposi sarcoma.

PMID- 9006389
TI  - Human herpesvirus 8 sequences are not detected in epithelial tumors from patients
      receiving transplants.

PMID- 9006390
TI  - Keloid formation with the 585-nm pulsed dye laser during isotretinoin treatment.

PMID- 9006392
TI  - Dermatitis herpetiformis following gastric surgery.

PMID- 9006391
TI  - Malignant hypercalcemia induced by a parathyroid hormone-related protein secreted
      by a cutaneous squamous cell carcinoma.

PMID- 9006393
TI  - Regrowth of alopecia areata simulating the pattern of androgenetic alopecia.

PMID- 9006394
TI  - Forty years of lithium treatment.
AB  - This review is based on a lecture in which I was requested to present my personal
      experiences and views. Since its introduction into psychiatry more than 40 years
      ago, lithium treatment has in most countries gained wide acceptance in the
      prophylaxis of unipolar and bipolar affective disorders. At one time it was
      feared that lithium treatment might lead to a decrease in the glomerular
      filtration rate, but systematically collected data indicate that even long-term
      treatment does not induce renal insufficiency. During treatment, regular
      laboratory monitoring of serum lithium and creatinine concentrations is
      recommended. Recent studies suggest that long-term lithium treatment does not
      raise the mortality of manic-depressive patients and indeed may have a mortality
      lowering and antisuicidal effect. Despite the availability of alternative
      therapies, lithium remains the treatment of choice for the prophylaxis of
      recurrent manic-depressive illness.

PMID- 9006395
TI  - Current therapeutic profile of lithium.

PMID- 9006396
TI  - Unanswered questions, unknown future for one of our oldest medications.

PMID- 9006397
TI  - A linkage study of bipolar illness.
AB  - BACKGROUND: Although genetic epidemiological studies of bipolar (BP) illness are
      consistent with a heritable component, inherited risk factors remain unknown. The
      goal of the present study is to describe the localization of BP susceptibility
      loci through linkage strategies, including a genome-wide search. METHODS: A
      linkage study of 22 BP families has been performed. These BP families include
      almost 400 persons, 173 of whom have been diagnosed as having BP I,
      schizoaffective, BP II with major depression, or recurrent unipolar illness.
      Using an autosomal dominant disease model with 85% or 50% age-dependent
      penetrance, and a recessive model with 85% penetrance, linkage analyses were
      performed assuming a narrow (BP and schizoaffective) or a broad (BP,
      schizoaffective, or unipolar) definition of the BP spectrum. Affected sibling
      pairs and affected pedigree member analyses were performed when positive lod
      scores were observed in multiple pedigrees. The present article describes linkage
      analysis of 310 DNA markers on chromosomes 1, 5p, 6, 8, 10q, 11q, and 12 to 18.
      RESULTS: None of the loci examined disclosed compelling evidence for linkage
      using lod score analyses. Model-independent analysis by multilocus affected
      pedigree member method in the pericentromeric chromosome 18 region disclosed
      statistically significant evidence (P < .0001) for a BP susceptibility gene in
      this region. Multilocus analysis by affected sibling pair method also disclosed
      evidence for linkage (P < .00008). CONCLUSIONS: Our results imply that a BP
      susceptibility gene exists near the centromere of chromosome 18. Confirmation of
      this finding (by independent investigators studying different pedigrees) has been
      published, suggesting that a valid BP disease linkage may have been discovered.

PMID- 9006398
TI  - Depression during mania. Treatment response to lithium or divalproex.
AB  - BACKGROUND: Little information exists from controlled studies about clinical
      characteristics that predict treatment response in mania. The presence of
      depressive symptoms during manic episodes may be associated with poor response to
      psychopharmacological treatments. This is an investigation of the relation
      between depressive symptoms and treatment response in acute manic episodes.
      METHODS AND DESIGN: In a parallel-group, double-blind study, 179 patients
      hospitalized for acute manic episodes were randomized to receive divalproex
      sodium, lithium carbonate, or placebo (ratio, 2:1:2). The study was carried out
      at 9 academic medical centers. Patients had comprehensive evaluations of behavior
      and symptoms before and during 3 weeks of treatment. The primary outcome measure,
      change in mania factor scores derived from the Schedule for Affective Disorders
      and Schizophrenia: Change Version, was compared in patients with and without
      depressive symptoms at baseline according to nurse- or physician-rated scales.
      RESULTS: Depressive symptoms were associated with poor antimanic response to
      lithium and with better response to divalproex. This was not due to differences
      in overall severity of illness, substance abuse, gender, age, or history.
      CONCLUSIONS: These data suggest that even a modest level of pretreatment
      depression-related symptoms is a robust predictor of lithium nonresponse, and is
      associated with better response to divalproex. Although their overall efficacy in
      acute mania is similar, lithium and divalproex may be most effective in
      clinically and biologically distinct groups of patients.

PMID- 9006399
TI  - No abnormality in the gene for the G protein stimulatory alpha subunit in
      patients with bipolar disorder.
AB  - BACKGROUND: The available evidence for an involvement of the heterotrimeric
      guanine-nucleotide-binding proteins (G proteins) in bipolar disorder relies
      primarily on the effects of lithium salts on G protein function and on
      alterations in the concentration or function of G proteins (most notably Gs
      alpha) in peripheral leukocytes and in postmortem tissues of patients with
      bipolar disorder. METHODS: The hypothesis that a mutation in Gs-alpha gene
      confers an increased susceptibility to bipolar disorder was tested by the
      following strategies: (1) mutational screening of the Gs-alpha subunit gene
      coding sequences and promoter sequences by denaturing gradient gel
      electrophoresis in unrelated individuals with bipolar disorder and (2)
      association and linkage analyses with a common silent exonic polymorphism, using
      genetic allelic information from American families with at least 1 affected
      child. For association analysis, the transmission test for linkage disequilibrium
      was used; for linkage analysis, nonparametric methods were used. RESULTS: No
      structural or regulatory mutations in this gene were found in bipolar disorder;
      the results of association and genetic linkage were negative. CONCLUSION: Our
      results do not support the speculation that the Gs-alpha protein gene has a role
      in the genetic predisposition to bipolar disorder.

PMID- 9006400
TI  - Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic
      treatment.
AB  - BACKGROUND: Abrupt discontinuation of long-term psychotropic medication can be
      followed by a high risk of early relapse. This study aimed to quantify the
      relapse risk over time in patients with schizophrenia following discontinuation
      of maintenance neuroleptic treatment. METHODS: Data on the timing of relapses in
      patients with schizophrenia after withdrawal from neuroleptic therapy were
      located by a computerized literature search, combined with new data, and
      evaluated by survival analysis. RESULTS: Data were found for 1210 schizophrenic
      subjects: 1006 (795 inpatients and 211 outpatients) were withdrawn abruptly from
      oral neuroleptic therapy, and 204 discontinued treatment gradually (> or = 3
      weeks) or stopped treatment with depot neuroleptic drugs. After abrupt
      discontinuation of oral medication, the risk of relapse reached 50% within 30
      weeks, with remarkably little additional risk thereafter to 3.7 years; inpatients
      relapsed more rapidly than did outpatients (10 vs 18 weeks to a 25% relapse
      risk). In studies including subjects whose drug therapy was withdrawn abruptly (n
      = 49) vs gradually (n = 58), relapse was earlier after abrupt discontinuation
      (25% risk in 6 vs 10 weeks), with a persistent difference for at least 6 months.
      CONCLUSIONS: The relapse risk was high within 6 months of discontinuing oral
      neuroleptic therapy, particularly in hospitalized patients. Most patients who
      remained stable for 6 months continued to do so for long periods without
      medication, indicating clinical heterogeneity. Drug-withdrawal stressors, related
      to long-term pharmacodynamic adaptations, are implicated. Since the risk was
      lower after gradually discontinuing oral neuroleptic therapy or stopping depot
      injections, early relapse may be spared by a slow removal of drugs.

PMID- 9006401
TI  - A prospective study of risk factors predicting grief intensity following
      pregnancy loss.
AB  - BACKGROUND: This prospective longitudinal study investigated which selected
      person-oriented, social environment, demographic, and pregnancy-related risk
      factors could best predict women's grief intensity following pregnancy loss.
      METHOD: In a prospective longitudinal study, 2140 pregnant women within 12 weeks'
      gestation answered a first questionnaire in writing. Of this sample, 227 women
      experienced an involuntary pregnancy loss and were followed up for a period of 18
      months, during which grief was reassessed four times, using the Perinatal Grief
      Scale. The prospectively measured risk factors were hierarchically ordered and
      linked to each woman's individual grief response over time. RESULTS: The
      hypothesized risk factors, with the exception of a prior pregnancy loss,
      significantly related to grief intensity following the pregnancy loss and
      together explained 35% of the variance in grief scores among subjects.
      Gestational age, preloss neurotic personality, preloss psychiatric symptoms, and
      family composition showed the strongest relation to grief intensity following a
      pregnancy loss. Only psychiatric symptoms showed an interaction with time in that
      the women who evidenced more psychiatric symptoms before the pregnancy loss
      showed more intense grief shortly following the pregnancy loss. The other risk
      factors had a constant effect, irrespective of the time that had passed since the
      loss. CONCLUSION: A relatively long preloss pregnancy, a more neurotic
      personality, more preloss psychiatric symptoms, and the absence of living
      children appear to be important risk factors for stronger grief responses in
      women following a pregnancy loss.

PMID- 9006402
TI  - Behavior of boys in kindergarten and the onset of substance use during
      adolescence.
AB  - BACKGROUND: The purpose of this study was to assess the usefulness of personality
      dimensions measured at ages 6 and 10 years in predicting early onset of cigarette
      smoking, alcohol abuse, and other drug use in boys. In addition, the stability of
      the prediction between the measurements at ages 6 and 10 years was investigated.
      METHODS: Data from a large longitudinal study of boys were used to assess the
      relation between childhood personality and the onset of substance use from 10 to
      15 years of age. Childhood personalities were assessed by teachers' ratings of
      behaviors. Self-reports of smoking cigarettes, getting drunk, and using other
      drugs provided the measurement of substance use. Discrete-time survival analysis
      was used for the statistical analyses. RESULTS: High novelty-seeking and low harm
      avoidance significantly predict early onset of substance use (eg, cigarettes,
      alcohol, and other drugs), but reward dependence was unrelated to any of the
      outcomes studied. The results also indicated that either set of predictors (ie,
      the personality dimensions measured at ages 6 and 10 years) could be used to
      predict onset of cigarette smoking, getting drunk, and other drug use, because
      the power of prediction was similar between the measurements at ages 6 and 10
      years. CONCLUSIONS: High novelty-seeking and low harm avoidance lead to early
      onset of substance use in boys. The stability of the prediction between ages 6
      and 10 years suggests that the kindergarten assessments may be used for
      preventive efforts at school entry instead of waiting until early adolescence.

PMID- 9006404
TI  - Psychiatric sequelae of posttraumatic stress disorder in women.
AB  - BACKGROUND: The risk for first-onset major depression, anxiety, and substance use
      disorders associated with prior posttraumatic stress disorder (PTSD) was
      estimated in a sample of women. METHODS: The National Institute of Mental Health
      Diagnostic Interview Schedule, revised according to DSM-III-R, was used to
      measure lifetime psychiatric disorders in a stratified random sample of 801
      mothers of children, who participated in a study of cognitive and psychiatric
      outcomes by level of birth weight. Cox proportional hazards models with time
      dependent covariates were used to calculate the hazards ratios of first onset of
      other disorders following PTSD. RESULTS: The lifetime prevalence of traumatic
      events was 40% and of PTSD, 13.8%. Posttraumatic stress disorder signaled
      increased risks for first-onset major depression (hazards ratio, 2.1) and alcohol
      use disorder (hazards ratio, 3.0). The risk for major depression following PTSD
      was of the same magnitude as the risk for major depression following other
      anxiety disorders. Women with preexisting anxiety and PTSD had significantly
      increased risk for first-onset major depression. Additional analysis showed that
      preexisting major depression increased women's vulnerability to the PTSD-inducing
      effects of traumatic events and risk for exposure to traumatic events.
      CONCLUSIONS: Posttraumatic stress disorder influences the risk for first-onset
      major depression and alcohol use disorder. The causal explanation of these
      temporally secondary disorders is unclear and might involve the effect of PTSD or
      underlying vulnerabilities exposed by the traumatic experience.

PMID- 9006405
TI  - Smoking affects plasma-soluble interleukin-2 receptor levels in patients with
      schizophrenia.

PMID- 9006403
TI  - Psychiatric and substance use comorbidity among treatment-seeking opioid abusers.
AB  - BACKGROUND: Major studies of psychiatric comorbidity in opioid abusers reported
      rates of comorbidity that far exceeded general population estimates. These
      studies were published more than a decade ago and reported on few women and few
      substance use diagnoses. METHODS: Psychiatric and substance use comorbidity was
      assessed in 716 opioid abusers seeking methadone maintenance. Diagnostic and
      Statistical Manual of Mental Disorders, Revised Third Edition diagnostic
      assessment was conducted 1 month after admission. Rates of psychiatric and
      substance use disorder were compared by gender, and associations were assessed
      between psychiatric comorbidity and dimensional indexes of substance use
      severity, psychosocial impairment, and personality traits. RESULTS: Psychiatric
      comorbidity was documented in 47% of the sample (47% women and 48% men).
      Antisocial personality disorder (25.1%) and major depression (15.8%) were the
      most common diagnoses. Patients had at least 2 substance use diagnoses, most
      often opioid and cocaine dependence. Demographics, substance use history, and
      personality variables discriminated between patients with vs without comorbidity.
      Psychiatric comorbidity also was associated with a more severe substance use
      disorder. CONCLUSIONS: Psychiatric comorbidity, especially personality and mood
      disorder, was common in men and women. The positive associations between
      psychiatric comorbidity and severity of substance use and other psychosocial
      problems were most consistent among those with antisocial personality.

PMID- 9006406
TI  - Please don't call me 'Arnold-Chiari' unless you mean it.

PMID- 9006407
TI  - Carcinomatous meningitis.

PMID- 9006408
TI  - The role of evoked potentials in coma.

PMID- 9006409
TI  - Quality-based medicine.

PMID- 9006410
TI  - Consensus against both endarterectomy and routine screening for asymptomatic
      carotid artery stenosis. Canadian Stroke Consortium.
AB  - BACKGROUND: Despite several randomized controlled trials, the role of carotid
      endarterectomy for asymptomatic patients is controversial. Validated evidence
      based guidelines are needed. METHODS: Thirty-five members of the Canadian Stroke
      Consortium, an independent body of cerebrovascular disease experts, reviewed
      evidence-based guidelines developed by the Canadian Task Force on the Periodic
      Health Examination. We held 3 rounds of Delphi consensus to solicit opinion and
      agreement. RESULTS: We found a high level of interrater agreement for all
      guidelines using multiple statistical measures. Members agreed that evidence is
      insufficient to endorse carotid endarterectomy for asymptomatic patients with
      angiographically proven stenosis of more than 60% (kappa = 0.70, P < .01).
      Reasons cited included concern over the reproducibility of low surgical morbidity
      rates in the community at large, the questionable clinical benefit conferred by
      surgery, and the lack of proven reduction in the risk of major disabling stroke.
      Screening the general population for asymptomatic stenosis was unanimously
      rejected. Also, screening even patients with risk factors or proven
      atherosclerosis at other sites was not endorsed (kappa = 0.91 and kappa = 0.79,
      respectively, both P < .01). CONCLUSIONS: There is insufficient evidence to
      recommend carotid endarterectomy for asymptomatic patients. Evidence is also
      insufficient to endorse a screening strategy even for patients with risk factors
      for carotid disease. While stroke prevention remains a critical goal, we do not
      recommend that it be accomplished by screening or by performing carotid surgery
      in asymptomatic patients.

PMID- 9006411
TI  - Presence and treatment of vascular risk factors in patients with vascular
      cognitive impairment.
AB  - OBJECTIVE: To document the presence and treatment of selected vascular risk
      factors in patients with vascular cognitive impairment and elements affecting
      undertreatment of vascular risk factors. DESIGN: Secondary analysis of the
      Canadian Study of Health and Aging database, which is a national, representative,
      cross-sectional study of the epidemiologic distribution of dementia in elderly
      people in Canada. SETTING: Survey. PATIENTS: Institutionalized and community
      dwelling elderly people. MAIN OUTCOME MEASURES: Vascular risk factors, dementia
      diagnosed by standard methods, and medication use. RESULTS: Treatable vascular
      risk factors occurred significantly more often in patients with vascular
      cognitive impairment (with and without dementia) than in patients with probable
      Alzheimer disease or normal cognitive function. For example, 76% of patients with
      vascular dementia and 57% of those with vascular cognitive impairment without
      dementia had a history of stroke, compared with only 5% of those with probable
      Alzheimer disease and 7% of those with no cognitive loss. (For hypertension, the
      comparable figures are 55%, 48%, 24%, and 38%, respectively.) Potential
      undertreatment of vascular risk factors had little effect on mean control of
      vascular risk factors. For example, the mean (+/- SD) systolic blood pressure in
      those being treated was 144 +/- 26 mm Hg, compared with 142 +/- 25 mm Hg in those
      not receiving pharmacological treatment. In each group (treated vs untreated),
      the proportion of patients with a systolic blood pressure higher than 160 mm Hg
      was 20% and 16%, respectively. Potential undertreatment occurred most often in
      those with severe dementia and those living in nursing homes. CONCLUSIONS:
      Vascular risk factors occurred more commonly in patients with vascular cognitive
      impairment compared with other patients, including those with other forms of
      dementia. When present, such risk factors were often treated pharmacologically,
      except in patients with severe dementia and those in long-term care institutions.
      Undertreatment does not, in general, result in worsened risk factor control.

PMID- 9006412
TI  - Giant lambl excrescences. An unusual source of cerebral embolism.
AB  - BACKGROUND: A possible association of giant Lambl excrescences (LEs) with stroke
      has been suggested. However, the treatment of giant LEs is controversial because
      minimal data are available. OBJECTIVE: To clarify the management of giant LEs
      through a clinicopathologic study. CASE SERIES: Three young patients (2 women and
      1 man) who experienced ischemic stroke were studied. Results of general
      examinations were normal, as were chest x-ray films, electrocardiograms,
      ultrasonograms of the neck, and cerebral angiograms. Extensive serological and
      blood testing failed to show any coagulopathies or systemic disorders that
      favored a stroke in these patients. Transesophageal echocardiography showed a
      mitral valve lesion (width, > 1 mm). Two patients (cases 1 and 3) were discharged
      on a regimen of anticoagulant therapy and sequential transesophageal
      echocardiographic monitoring was planned, whereas 1 patient (case 2) was promptly
      scheduled for surgery. A second stroke occurred in patients 1 and 3 at 3 and 6
      months, respectively, thus leading to surgery in these 2 patients. Findings from
      histopathologic studies were consistent with the diagnosis of giant LEs. The
      patients' outcomes were uneventful after surgery, and none had a recurrence of a
      stroke. CONCLUSIONS: A relationship between giant LEs and stroke may be
      suggested. In patients who have transesophageal echocardiographic findings that
      are consistent with this diagnosis and recurrent stroke despite antithrombotic
      therapy and without an alternative explanation for the ischemic symptoms, surgery
      should be considered in view of these findings.

PMID- 9006413
TI  - Familial juvenile focal amyotrophy of the upper extremity (Hirayama disease).
      Superoxide dismutase 1 genotype and activity.
AB  - BACKGROUND: Juvenile focal amyotrophy of the arm is an unusual focal motor neuron
      disease that is rarely familial. Its pathogenesis is unknown. We recently
      described a family with amyotrophic lateral sclerosis associated with a mutation
      in the superoxide dismutase 1 (SOD1) gene substituting an aspartate for an
      alanine (D9OA). One of the carriers of this mutation had focal and nonprogressive
      amyotrophy of the arm, suggesting that focal amyotrophy might be associated with
      SOD1 mutations. OBJECTIVES: To describe the phenotype of 2 brothers with juvenile
      focal amyotrophy of the upper extremity and to characterize their SOD1 genotype
      and SOD activity. METHODS: Polymerase chain reaction and sequencing of the SOD1
      gene and colorimetric measurement of the enzyme activity. RESULTS: We compared
      the phenotype of our patients to that of 375 patients described in the Western
      literature. The 5 exons of the SOD1 gene were normal, as was the SOD activity in
      red blood cells.

PMID- 9006414
TI  - The natural course of cerebral lesions in Sneddon syndrome.
AB  - OBJECTIVES: To characterize the clinical, biological, and neuroradiological
      findings in Sneddon syndrome; to correlate magnetic resonance imaging
      abnormalities with disability, presence of hypertension and other vascular risk
      factors, presence of heart valvulopathy on echography, and titer of
      antiphospholipid antibodies; and to compare these findings in antiphospholipid
      positive and antiphospholipid-negative patients. DESIGN: Retrospective review of
      the records of 32 consecutive patients with livedo reticularis and neurological
      events, followed up in our institution between January 1991 and August 1995.
      PATIENTS: Twenty-six patients (20 women and 6 men) who had at least 1 cerebral
      ischemic arterial event associated with generalized and pathological livedo
      reticularis. RESULTS: The age at the first cerebral ischemic event ranged from 22
      to 58 years. Motor deficit was the most frequent sign (found in 73% of cases).
      Disability was found in 50%, systemic hypertension in 65%, heart valvulopathy in
      61%, and antiphospholipid antibodies in 42% of cases. Patients were classified in
      6 groups according to magnetic resonance imaging findings. No correlation was
      found between the presence of hypertension or other vascular risk factors,
      valvulopathy, antiphospholipids, and magnetic resonance imaging abnormalities.
      There was no significant difference between antiphospholipid-positive and
      antiphospholipid-negative patients except for the presence of antinuclear
      antibodies. There was a significant correlation between the extent of magnetic
      resonance imaging abnormalities and disability. CONCLUSION: The severity of the
      disease seems to be correlated with magnetic resonance imaging aspects, but not
      to the presence of antiphospholipid antibodies. Magnetic resonance imaging may
      help to understand the natural course of the cerebral involvement of the disease.

PMID- 9006415
TI  - A new family with periventricular nodular heterotopia and peculiar dysmorphic
      features. A probable X-linked dominant trait.
AB  - OBJECTIVE: To describe 3 sisters with brain periventricular heterotopia and
      peculiar dysmorphic features as a probable X-linked dominant trait. DESIGN:
      Clinical, laboratory, neurophysiological, and brain imaging data were studied.
      SETTING: Research institute for mental retardation. PATIENTS: The 3 sisters had
      mental retardation, drug-resistant epilepsy, gray matter heterotopia, and
      peculiar malformations (low nasal bridge, upslanting palpebral fissures,
      palpebral edema, attached hypoplastic earlobes, thickened calvaria, rectal
      fibrovascular polyps, urinary tract anomalies, and increased foot length). The
      patients were 35, 30, and 25 years old and belonged to a sibship of 6, born of
      nonconsanguineous healthy parents. CONCLUSION: The 3 patients constitute a well
      defined clinical entity not previously described of a probable X-linked dominant
      nature.

PMID- 9006416
TI  - Specificity of volumetric magnetic resonance imaging in detecting hippocampal
      sclerosis.
AB  - BACKGROUND: Magnetic resonance imaging (MRI)-based volumetric measurements of the
      hippocampal formation are useful in detecting unilateral hippocampal sclerosis
      (HS) in patients with temporal lobe epilepsy. In this pathologic entity,
      volumetric MRI analysis shows the epileptogenic structure to be atrophic when
      compared with the normal, nonepileptogenic side. Some authors have suggested that
      the radiological features of atrophy of medial temporal lobe structures are
      common in patients with complex partial seizures, but also are seen frequently in
      other seizure types and can occur even in patients without epilepsy. OBJECTIVE:
      To determine if seizures originating in extrahippocampal sites cause gliosis,
      cell loss, and atrophy of medial temporal lobe structures (i.e., HS). METHODS: We
      studied 110 patients with chronic epilepsy using volumetric MRI measurements of
      the hippocampal formation. Seventeen patients had pathologically proven HS, 27
      patients had seizures due to extratemporal structural lesions, 15 patients had
      seizures caused by extrahippocampal temporal lobe lesions, 29 patients had
      primary generalized epilepsy, and 22 patients had secondary generalized epilepsy.
      RESULTS: All 17 patients with HS showed significantly reduced absolute
      hippocampal formation volumes of greater than 2 SDs below the mean of the control
      groups. The preoperative hippocampal formation volume measurements correlated
      well with the severity of HS on pathological examination. Hippocampal volumes
      were within the normal range in all patients with primary generalized epilepsy,
      secondary generalized epilepsy, extratemporal structural lesions, and
      extrahippocampal temporal lobe lesions. CONCLUSIONS: Seizures originating at
      extrahippocampal sites do not cause gliosis, cell loss, or atrophy of medial
      temporal structures. Significant reduction in hippocampal volumes is a specific
      marker for HS.

PMID- 9006417
TI  - HLA typing in acute optic neuritis. Relation to multiple sclerosis and magnetic
      resonance imaging findings.
AB  - OBJECTIVE: To study the association of brain magnetic resonance imaging (MRI)
      findings and HLA findings to clarify the relationship between monosymptomatic
      optic neuritis (ON) and ON as part of clinically definite multiple sclerosis
      (CDMS). DESIGN: Population-based cohort of patients with ON referred
      prospectively during 6 years by neurologists and ophthalmologists within 4 weeks
      of onset of ON. SETTING: Referral center in the general community of greater
      Copenhagen (Denmark) (population, 1.5 million). PATIENTS: A consecutive sample of
      199 patients aged 12 to 59 years with ON (133 with idiopathic ON, 66 with ON +
      CDMS), ethnically matched with 192 healthy volunteers. MAIN OUTCOME MEASURES:
      Relation between the HLA-DR15, -DR17, -DQA-1B, and -DQB-1B polymorphisms as
      defined by restriction fragment length polymorphism analysis, and presence of
      plaques on T2-weighted brain MRI. RESULTS: The frequency of HLA-DR15 was
      significantly increased in patients with ON + CDMS (52%) and ON (47%) compared
      with control subjects (31%). The frequency of HLA-DR17 was almost equal in the ON
      + CDMS (18%), ON (23%), and control (23%) groups. The frequencies of HLA-DQA-1B
      (55% in ON + CDMS, 58% in ON) and HLA-DQB-1B (49% in ON + CDMS, 59% in ON) were
      significantly increased compared with control subjects (41%, HLA-DQA-1B; 37%, HLA
      DQB-1B). Brain MRI was abnormal in 48 of 56 examined patients with ON + CDMS and
      in 64 of 120 examined patients with ON (P < .001). In contrast, the frequencies
      of HLA alleles did not differ between patients with and without demyelinating
      lesions. However, patients with ON and normal MRI findings did not show
      association with HLA-DR15. CONCLUSIONS: The frequencies of alleles were similar
      in patients with ON and ON + CDMS, confirming that they are not 2
      immunogenetically distinct disease entities. The heterogeneity within the group
      of patients with ON suggests that the HLA-DR15 molecule is involved in
      susceptibility to initial demyelinating lesion formation.

PMID- 9006418
TI  - Stroke associated with cardiac surgery. Determinants, timing, and stroke
      subtypes.
AB  - OBJECTIVE: To determine the nature of strokes complicating cardiac surgery.
      DESIGN: A medical record review was undertaken of all patients who underwent
      cardiac surgery (either coronary bypass, valvular surgery, or both) between
      January 1990 and July 1995. Univariate and multivariate analyses were done using
      odds ratios (ORs) and logistic regression. RESULTS: A total of 2211 patients
      underwent cardiac surgery. A total of 44 patients (2%) had postoperative strokes.
      They were compared with 104 surgical controls. Univariate analysis revealed that
      the patients with stroke were significantly older and had significantly higher
      rates of transient ischemic attack, congestive heart failure, and peripheral
      vascular disease by history. A multivariate logistic regression revealed the
      significant variables associated with stroke were congestive heart failure (OR,
      6.8) and transient ischemic attack (OR, 1.2). Analyses of surgical variables
      revealed that bypass pump time of more than 120 minutes (OR, 1.40) was the only
      significant predictor. The majority of strokes (61%) had occurred by
      postoperative day 2, but 39% occurred between postoperative days 3 to 9.
      Hemispheric syndromes occurred in 70%, brain stem and cerebellar syndromes in
      14%, and lacunar syndromes in 16%. Computed tomographic scans revealed that 29
      patients had new infarcts, of which 20 (69%) were territorial, 5 (17%) were small
      deep, and 4 (14%) were border zone. Hemorrhagic infarction was found in 2 cases
      (5%). One patient (2.5%) had a cardiorespiratory arrest while undergoing computed
      tomography. Discharge disposition was good in 88% of patients with stroke (12%
      with poor outcomes) vs 97% of controls with good outcomes (3% with poor outcomes)
      (P = .04). CONCLUSIONS: Strokes may be delayed following cardiac surgery perhaps
      because of ongoing risk of embolism or a hypercoagulable state. A surprisingly
      high proportion of patients have lacunar syndromes or small-deep infarcts shown
      on computed tomography. Early computed tomographic imaging may be useful to
      exclude hemorrhage if anticoagulation is considered, but is not without risk in
      these potentially unstable patients. Greater understanding of risk factors for
      stroke, timing, and subtypes may ultimately allow identification of patients at
      particularly high risk for perioperative stroke.

PMID- 9006419
TI  - Motor neuron disease and angiotropic lymphoma.
AB  - BACKGROUND: The number of patients with motor neuron disease (MND) and a
      concomitant hematologic disorder appears to be overrepresented. Angiotropic large
      cell lymphoma, a rare and aggressive type of lymphoma, has been associated with
      MND only once (to our knowledge) prior to this report. There are more than 35
      cases of MND associated with lymphoma or monoclonal gammopathy reported in the
      literature. The nature of this association remains disputable. OBJECTIVE: To
      investigate whether the association between some MNDs and certain hematologic
      disorders is coincidental or pathogenetically related. CASE PRESENTATION: We
      describe the clinical and neuropathologic findings in a case involving a 70-year
      old man with a rapidly progressive lower MND who at autopsy also exhibited
      angiotropic large cell lymphoma without ischemic lesions in the nervous system.
      CONCLUSIONS: This case supports the notion that the association between some MNDs
      and certain hematologic disorders is not coincidental but pathogenetically
      related. A 2-hit hypothesis is proposed in which an initial abnormal
      glycosylation in motoneurons would require the production of an appropriate
      autoantibody for disease expression.

PMID- 9006420
TI  - Vitrectomy for the treatment of full-thickness stage 3 or 4 macular holes.
      Results of a multicentered randomized clinical trial. The Vitrectomy for
      Treatment of Macular Hole Study Group.
AB  - OBJECTIVE: To prospectively assess the risks and benefits of vitrectomy surgery
      for eyes with stage 3 or 4 macular holes. DESIGN: A multicentered, controlled,
      randomized clinical trial. SETTING: Community- and university-based ophthalmology
      clinics. PATIENTS: One hundred twenty patients (129 eyes) with stage 3 or 4
      macular holes. INTERVENTIONS: Standardized macular hole surgery vs observation
      alone. MAIN OUTCOME MEASURES: Four measures of best-corrected visual function,
      standardized photographic evaluation of the extent of hole closure, evaluation of
      lens opacification, and determination of adverse events. Outcomes were determined
      at 6 months after randomization. RESULTS: Compared with observation alone, a
      significant benefit due to surgery was found in the rate of hole closure (4% vs
      69%, P < .001). After adjusting for baseline visual acuity, hole duration, and
      maximum hole diameter, a significant benefit due to surgery was found in visual
      acuity for the Bailey-Lovie Word Reading (P = .02) and the Potential Acuity Meter
      (P < .01) tests; a marginally significant benefit due to surgery was found in
      visual acuity for the Early Treatment Diabetic Retinopathy Study chart (P = .05).
      Although the proportion of eyes achieving a change in visual acuity of 2 or more
      lines on the Early Treatment Diabetic Retinopathy Study chart was significantly
      greater for the surgery group vs the observed group (11 [19%] of 59 eyes vs 3
      [5%] of 58 eyes, adjusted P = .05), 20 (34%) of 59 eyes randomized to surgery had
      a loss in visual acuity of 1 or more lines. Compared with the observation group,
      eyes randomized to surgery had higher nuclear sclerosis scores (2.4 vs 1.3, P <
      .001). Fourteen adverse events were noted in the surgery group; none were noted
      in the observed group. CONCLUSIONS: Some visual benefit of vitrectomy surgery for
      macular holes exists, despite a notable incidence of adverse events. The large
      variability in visual acuity outcome in the surgical group may be because of
      complications or progressive cataract. A study of the long-term outcome after
      macular hole surgery is needed.

PMID- 9006421
TI  - Motion perimetry identifies nerve fiber bundlelike defects in ocular
      hypertension.
AB  - OBJECTIVE: To determine whether patients with ocular hypertension (OHT) have
      elevated motion perimetry thresholds. DESIGN: Motion perimetry uses a customized
      computer graphics program to detect the ability to identify a coherent shift in
      position of 50% of dots in a defined circular area against a background of fixed
      dots. Motion size threshold is defined as the smallest circular area in which dot
      motion is detected. Subjects respond by touching the area of the computer monitor
      with a light pen where motion stimuli are perceived. Reaction times
      (milliseconds) to stimuli and localization error (number of pixels from target
      center) are also obtained for each trial. SETTING: University hospital
      ophthalmology clinic. PATIENTS OR OTHER PARTICIPANTS: Twenty-seven patients with
      OHT and 27 age-matched normal subjects. One eye was tested in each subject. MAIN
      OUTCOME MEASURES: Random dot motion stimuli size thresholds and total deviation
      probability plot data, reaction times, and spatial localization errors. RESULTS:
      The patients with OHT had more abnormal test points in the total deviation
      probability plot analysis compared with the controls (P < .001, chi 2). The
      abnormal test points were concentrated in the superior and inferior nasal
      regions. Six subjects had nerve fiber bundlelike defects to motion stimuli. Six
      subjects (5 overlapping with the probability plot analysis) had abnormal glaucoma
      hemifield test results. The patients with OHT also had significantly greater
      localization errors. CONCLUSION: Motion threshold perimetry may be a more
      sensitive method to detect visual field abnormalities in OHT than conventional
      automated perimetry.

PMID- 9006422
TI  - Acute and chronic conjunctivitis due to over-the-counter ophthalmic
      decongestants.
AB  - OBJECTIVE: To describe patterns of conjunctivitis caused by ophthalmic
      decongestants. DESIGN: Case series. SETTING: Outpatient eye clinic. PATIENTS: We
      selected patients with conjunctival inflammation who were using nonprescription
      decongestant eyedrops, who had no other cause for conjunctivitis, and whose
      conditions improved after discontinuing the incriminated preparations. MAIN
      OUTCOME MEASURES: Clinical characteristics of conjunctival inflammation and time
      to resolution of symptoms and signs after discontinuing the use of eyedrops.
      RESULTS: Seventy patients (137 eyes) were identified. Preparations containing the
      vasoconstrictors naphazoline, tetrahydrozoline, or phenylephrine were associated
      with 3 clinical patterns of conjunctivitis: conjunctival hyperemia (50 cases),
      follicular conjunctivitis (17 cases), and eczematoid blepharoconjunctivitis (3
      cases). Decongestants were used daily for a median of 3 years (range, 8 hours to
      20 years) prior to presentation. The median time to resolution of symptoms and
      signs was 4 weeks (range, 1-24 weeks), and patients remained asymptomatic for a
      median follow-up of 6 months (range, 0-12 years). CONCLUSION: Nonprescription
      decongestant eyedrops can produce acute and chronic forms of conjunctivitis by
      pharmacological, toxic, and allergic mechanisms. Once recognized, conjunctival
      inflammation often takes several weeks to resolve.

PMID- 9006423
TI  - The contralateral corneal endothelium in the iridocorneal endothelial syndrome.
AB  - OBJECTIVE: To evaluate the corneal endothelial morphometric measures of the
      contralateral, clinically uninvolved eye of patients with the iridocorneal
      endothelial (ICE) syndrome. DESIGN: A retrospective review of the specular
      microscopic photographs of the contralateral corneal endothelium of all patients
      with ICE syndrome seen at Mayo Clinic, Rochester, Minn. SETTING: Ophthalmology
      department, Mayo Clinic. PARTICIPANTS: Twenty-eight patients with unilateral ICE
      syndrome who had bilateral endothelial photographs (ICE group) and 28 normal, age
      matched control subjects (control group). MAIN OUTCOME MEASURES: Percentage of
      hexagonal cells, coefficient of variation of cell area, and endothelial cell
      density. METHODS: For each patient and control, 100 endothelial cells were
      digitized from projected endothelial photomicrographs of the central corneas in
      the uninvolved eyes. RESULTS: A statistically significant decrease was noted in
      the mean percentage of hexagonal cells (ICE, 62%; control, 69%; P = .002), and an
      increase was noted in the mean coefficient of variation of cell area (ICE, 0.28;
      control, 0.25; P = .02) in the patients with ICE syndrome compared with normal,
      age-matched controls. The mean endothelial cell density did not differ
      significantly between the 2 groups (ICE, 2588; control, 2759; P = .10).
      CONCLUSION: Our data suggest that the clinically uninvolved, contralateral eyes
      in patients with ICE syndrome have subclinical endothelial abnormalities as
      evidenced by a relatively low percentage of hexagonal cells and a relatively high
      coefficient of variation of cell area.

PMID- 9006424
TI  - Comparison of dorzolamide and acetazolamide as suppressors of aqueous humor flow
      in humans.
AB  - OBJECTIVE: To compare the efficacy of topical 2% dorzolamide hydrochloride
      (Trusopt) as a suppressor of aqueous humor flow in the human eye with the
      efficacy of systemically administered acetazolamide (Diamox). DESIGN: A
      randomized, double-masked, placebo-controlled study of 40 human subjects in 2
      academic centers. The effect of dorzolamide on aqueous humor flow was compared
      with that of acetazolamide as measured by the rate of clearance of topically
      applied fluorescein. RESULTS: Acetazolamide reduced aqueous flow from 3.18 +/-
      0.70 (mean +/- SD) to 2.23 +/- 0.48 microL per minute, a reduction of 30% (P <
      .001), and dorzolamide reduced the flow to 2.65 +/- 0.64 microL per minute, a
      reduction of 17% (P < .001). The difference between the effect of acetazolamine
      and dorzolamide was significant (P < .001). When acetazolamide is added to
      dorzolamide, the aqueous flow was reduced further to 2.21 +/- 0.47 microL per
      minute, an additional reduction of 16% (P < .001). When dorzolamide was added to
      acetazolamide, no additional reduction was observed (P = .73). Similar effects
      were observed for intraocular pressure. Acetazolamide reduced pressure from 12.5
      +/- 2.2 (mean +/- SD) to 10.1 +/- 2.2 mm Hg, a decrease of 19% (P < .001) and
      dorzolamide reduced it to 10.8 +/- 2.1 mm Hg, or a decrease of 13% (P < .001).
      The greater effect of acetazolamide than dorzolamide was significant (P = .03).
      CONCLUSIONS: For reasons that are not known, the topically applied carbonic
      anhydrase inhibitor 2% dorzolamide hydrochloride is not as effective as
      systemically administered acetazolamide. Clinicians who prescribe dorzolamide
      should expect less of an ocular hypotensive effect than that experienced from
      systemically administered acetazolamide.

PMID- 9006425
TI  - Relationship between difficulty in performing daily activities and clinical
      measures of visual function in patients with retinitis pigmentosa.
AB  - OBJECTIVES: To assess the level of perceived difficulty experienced by patients
      with retinitis pigmentosa (RP) in the performance of everyday activities and to
      determine the correlation between patients' self-reported difficulty and clinical
      measures of visual function. METHODS: One hundred sixty-seven patients with
      typical RP and Usher syndrome type 2, with a wide range of disease severity,
      rated their difficulty in the performance of 33 activities. We obtained data on
      visual acuity and visual field area for all patients, and electroretinogram (ERG)
      recordings on a subgroup of 49 of these patients. Results from the questionnaire
      were analyzed with factor analysis, and patients' self-reports were compared with
      their clinical data using correlational analyses and multiple regression.
      RESULTS: The patients' questionnaire responses clustered into 6 factors:
      activities involving central vision, miscellaneous activities (no discernible
      common factor), activities related to mobility, driving, negotiating steps, and
      eating meals. Of the clinical tests, visual acuity was most strongly related to
      the patients' ratings of their difficulty in performance. Visual field area also
      was related to patients' self-assessments but not as strongly as visual acuity.
      Because visual field area and the ERG measures were correlated, adding ERG
      information did not improve predictability. CONCLUSIONS: In patients with RP,
      perceived difficulty in performing common tasks was most strongly related to
      level of visual acuity and visual fields. Although certain ERG amplitude measures
      did show positive correlations with some self-reported activities, overall, the
      ERG amplitude measures showed the least relationship with patients' self-reports.
      Our results provide insight into RP patients' perceived difficulties in
      performing everyday activities and the clinical measures of visual function that
      most highly correlate with these difficulties.

PMID- 9006426
TI  - Uveitis associated with inflammatory bowel disease compared with uveitis
      associated with spondyloarthropathy.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) and spondyloarthropathy (SA) such as
      Reiter syndrome may be characterized by diarrhea, arthritis, stomatitis, and
      uveitis. OBJECTIVE: To determine if the characteristics of the eye disease could
      help distinguish these 2 diagnoses. DESIGN: Seventeen patients with uveitis and
      IBD referred to a university clinic were compared retrospectively with 89
      patients with uveitis and SA referred to the same clinic. RESULTS: Twelve (80%)
      of the 15 patients with evaluable IBD had Crohn disease. In marked contrast to
      patients with SA, patients with IBD were usually female (82%). Whereas uveitis
      with SA was predominantly anterior, unilateral, sudden in onset, and limited in
      duration, patients with IBD frequently had uveitis that was bilateral, posterior,
      insidious in onset, and/or chronic in duration. Results for 89% of the patients
      with SA who underwent HLA-B27 typing were positive, compared with only 46% of
      such patients with IBD. Episcleritis, scleritis, and glaucoma were more common
      among patients with IBD. Arthritis did not easily distinguish the 2 groups, as 13
      (76%) of the patients with IBD had a history of joint disease. In 10 (59%) of the
      patients with IBD, the diagnosis of uveitis preceded that of IBD. CONCLUSION: The
      hallmarks of uveitis can often distinguish SA and IBD.

PMID- 9006427
TI  - Sudden death in septo-optic dysplasia. Report of 5 cases.
AB  - OBJECTIVES: To report our experience with sudden death in children with septo
      optic dysplasia and to identify specific risk factors and suggest preventive
      measures to minimize mortality. METHODS: Clinical data from 5 children with septo
      optic dysplasia who died suddenly and unexpectedly were evaluated
      retrospectively. RESULTS: All children had corticotropin deficiency, all had
      thermoregulatory disturbances, and 4 children had diabetes insipidus. In at least
      4 children, clinical deterioration was caused by fever and dehydration from a
      presumed viral illness, which appeared to precipitate adrenal crisis.
      CONCLUSIONS: Children with septo-optic dysplasia and hypocortisolism are at risk
      for sudden death during febrile illness. Thermoregulatory disturbances and
      dehydration from diabetes insipidus may potentiate clinical deterioration.
      Prevention of sudden death in septo-optic dysplasia requires early recognition
      and treatment of these major risk factors.

PMID- 9006428
TI  - An anatomical basis for primary acquired nasolacrimal duct obstruction.
AB  - OBJECTIVE: To measure any sex size differences in the bony nasolacrimal drainage
      systems in a normal, age-matched population. METHODS: A retrospective study of
      axial cut maxillofacial computed tomographic scans was conducted. Three levels of
      the bony nasolacrimal duct (NLD) system on the right and left sides were measured
      along the anteroposterior diameter. The data were analyzed using 2-tail t test,
      analysis of variance, and linear regression methods. RESULTS: Scans from 71 adult
      patients (36 men and 35 women) were reviewed. Women were found to have a smaller
      bony diameter at the level of the lower fossa (P = .01) and the middle NLD (P =
      .06) compared with those of men. The adult inferior bony fossa increased in size
      with age in both men and women, while the middle NLD increased in size in men
      only. No significant size difference was found between the right and left side at
      any level. CONCLUSIONS: Size differences are found in measurements of bony
      nasolacrimal excretory systems in men vs women. Women have significantly smaller
      dimensions in the lower nasolacrimal fossa and the middle NLD. The
      anteroposterior dimension of the bony nasolacrimal canal at the fossa level
      enlarged in both sexes, with age co-inciding with osteoporotic changes throughout
      the body. These quantitative anatomical observations provide a contributory
      factor to explain the increased prevalence of primary acquired NLD obstruction in
      women.

PMID- 9006429
TI  - Secondary squamous cell carcinoma of the orbit.
AB  - OBJECTIVE: To evaluate the origin and biological behavior of secondary orbital
      squamous cell (SCC) and mucoepidermoid carcinoma. METHODS: A retrospective review
      of 30 consecutive patients with SCC and mucoepidermoid carcinoma of the orbit
      seen over a period of 8 years at a large ophthalmic hospital in Saudi Arabia.
      RESULTS: A total of 51 secondary orbital tumors were seen in the 8-year period
      from 1983 through 1991; 30 (60%) of the 51 cases were SCC. There were 16 male and
      14 female patients, with an age range of 38 to 80 years and a mean age of 65
      years. In 28 (93%) of the 30 patients, the tumor originated in the conjunctiva.
      Orbital involvement by conjunctival SCC was the most common cause of secondary
      orbital tumors encountered in patients older than 19 years. Four patients had
      concomitant paranasal sinus involvement, 4 patients exhibited intraocular
      invasion, and 2 others were found to have intracranial extension of the SCC. Six
      (20%) of the 28 patients developed regional lymph node metastases during the
      course of their illness. All patients were treated by orbital exenteration, with
      or without radiation therapy. Seven (23%) of the 28 patients died of their
      disease. CONCLUSIONS: Orbital SCC is an aggressive and life-threatening
      condition. Most cases result from secondary extension of conjunctival SCC, a
      common disease in Saudi Arabia. Several factors contribute to the aggressiveness
      of conjunctival SCC in this geographic location, including continual exposure to
      UV rays, chronic irritation, and genetic factors. Delay in presentation for
      treatment, inadequate initial resection of conjunctival lesions, and the
      aggressive mucoepidermoid carcinoma variant of SCC are also factors contributing
      to orbital invasion.

PMID- 9006430
TI  - Corneal endothelial damage by air bubbles during phacoemulsification.
AB  - OBJECTIVE: To characterize the mechanism by which air bubbles damage the corneal
      endothelium during phacoemulsification. MATERIALS AND METHODS: A series of
      experiments was conducted to expose the corneal endothelium of New Zealand white
      rabbit and human eyes that were obtained from an eye bank to air under different
      conditions. Phacoemulsification at different power settings and irrigation with
      and without the introduction of air into the anterior chamber were performed.
      Corneal endothelial perfusion experiments were conducted with air bubbles that
      were introduced into the perfusion chamber for 2 seconds to 1 hour. Air was also
      injected into the anterior chambers of anesthetized rabbits for 2 minutes to 3
      hours. Corneas were stained with nitrobenzo-xadiazole-phallacidin and examined
      with fluorescence microscopy. Selected corneas were also examined with scanning
      and transmission electron microscopy. RESULTS: Intracameral air bubbles during
      phacoemulsification, irrigation, and perfusion studies resulted in a severe
      injury to the corneal endothelium in as little as 20 seconds. Intracameral air
      bubbles in a living rabbit resulted in a slower injury that was morphologically
      different from the more rapid injury. CONCLUSIONS: Air bubbles in intraocular
      fluids with a high surface tension can cause a ring-shaped pattern of damage to
      the corneal endothelium. The mechanism that caused this pattern of damage appears
      to be a surface tension phenomenon.

PMID- 9006431
TI  - Isolation and culture of iris pigment epithelium from iridectomy specimens of
      eyes with and without exfoliation syndrome.
AB  - OBJECTIVE: To culture iris pigment epithelium (IPE) from surgical iridectomy
      specimens of eyes with and without exfoliation syndrome. METHODS: The IPE was
      treated to obtain a single cell suspension. Cells were cultured in Ham F12
      nutrient mixture, which was supplemented with 30% fetal bovine serum, 50
      micrograms/mL [corrected] gentamicin, and 2-mmol/L glutamine. After confluence,
      the cells were detached using a 0.125% trypsin-0.01% edetic acid solution,
      resuspended, diluted, and subcultured. The IPE from primary cultures and
      subcultures was studied by transmission electron microscopy. Immunocytochemical
      staining was performed. RESULTS: In the primary cultures of IPE from patients
      with exfoliation syndrome, curved, cross-banded, fine fibrils (diameter, 10-15
      nm; periodicity, 10-14 nm) were found on the cell surface. Thicker fibrils
      (diameter, 24-48 nm; periodicity, 24-36 nm) were found external to the fine
      fibrils. Subcultures contained mainly fine fibrils. The IPE cells stained
      positively with anticytokeratin, S100 protein, and vimentin antibodies.
      CONCLUSION: Iris pigment epithelium can be successfully cultured from eyes with
      exfoliation syndrome. Studying the production of exfoliation material in vitro
      should provide information about the pathogenesis of exfoliation syndrome and
      about the nature of the exfoliation material. The cultivation of normal IPE from
      surgical specimens provides a source for the study of the growth regulation and
      pharmacophysiology of IPE in vitro.

PMID- 9006432
TI  - Clinical and genetic analysis of a family affected with dominant optic atrophy
      (OPA1)
AB  - OBJECTIVES: To refine the dominant optic atrophy locus, OPA1, on chromosome 3q
      and to characterize the phenotype of a 6-generation family pedigree affected with
      this disease. METHODS: Fifty-six family members had a complete eye examination.
      Clinical records of an additional 3 patients were reviewed. Goldmann perimetry
      and a 21-chip subtest of the Farnsworth-Munsell 100-Hue test were performed on
      selected patients. Affected patients, unaffected siblings, and potentially
      informative spouses were genotyped with short tandem repeat polymorphisms located
      on chromosome 3. The genotypic data were subjected to linkage analysis. RESULTS:
      Thirty-four family members were found to be clinically affected. Most experienced
      vision loss (20/40 or poorer) in the first decade of life. Most (9 of the 16
      eyes) progressed to 20/800 or poorer visual acuity by age 60 years, while 2
      patients maintained visual acuities of 20/40 at that age. Affected patients had a
      2- to 10-fold increase in the error score of a 21-chip subtest of the Farnsworth
      Munsell 100-Hue test compared with age-matched unaffected family members. The
      optic nerve examination revealed temporal pallor and excavation in all affected
      individuals. Linkage analysis revealed significant lod scores with 9 markers. The
      highest lod score, 10.1 (theta = 0) [corrected], was obtained with marker
      D3S2305. Analysis of recombinants narrowed the disease interval to approximately
      3.8 centimorgans, flanked by D3S3669 (centromeric) and D3S1305 (telomeric).
      CONCLUSIONS: Most patients affected with dominant optic atrophy in this family
      progressed to legal blindness by middle age. Color vision testing is a sensitive
      method for detection of affected patients. The dominant optic atrophy locus,
      OPA1, has been refined by the identification of new flanking markers: D3S3669
      (centromeric) and D3S1305 (telomeric).

PMID- 9006434
TI  - Prevalence of lens opacities in the Barbados Eye Study.
AB  - OBJECTIVE: To present population-based data on type and extent of age-related
      lens opacities in the predominantly black population of the Barbados Eye Study.
      DESIGN: Prevalence study. SETTING AND PARTICIPANTS: The Barbados Eye Study
      included 4709 participants (84% of those eligible), who were identified from a
      random sample of Barbadian-born citizens aged 40 to 84 years. DATA COLLECTION:
      Lens gradings at the slit lamp, obtained with the use of the Lens Opacities
      Classification System II. MAIN OUTCOME MEASURE: Prevalence of posterior
      subcapsular, nuclear, and cortical opacities (defined as a grade > or = 2 in
      either eye), as well as prevalence of any lens changes (including history of
      previous cataract surgery and/or cataract too advanced to grade). RESULTS:
      Overall, 41% of the Barbados Eye Study population had any lens changes, including
      3% with aphakia or an intraocular lens. Among the population of African descent,
      cortical opacities (34%) were most prevalent, followed by nuclear (19%) and
      posterior subcapsular (4%) opacities. Prevalence of all opacity types increased
      with age (P < .001). Cortical and nuclear opacities were more frequent in women
      than men. When prevalence of a single kind of opacity was considered, 21% of
      participants had cortical only, 6% had nuclear only, and 0.4% had posterior
      subcapsular only; 13% had mixed opacities. Visual acuity loss to worse than 20/40
      in the more affected eye was present in 48%, 26%, and 18% of nuclear only,
      posterior subcapsular only, and cortical only types, respectively, and in 53% of
      mixed opacities. CONCLUSIONS: The Barbados Eye Study provides the first
      prevalence data on different types of lens opacities in a large, predominantly
      black population. Whereas nuclear opacities are most common in white populations,
      cortical opacities were the most frequent type in the Barbados Eye Study, a
      finding of possible etiologic relevance. Other results highlight a higher
      frequency of opacities in women than men and a high prevalence of visual acuity
      loss in affected eyes.

PMID- 9006435
TI  - Verdict on macular hole surgery. More data needed.

PMID- 9006436
TI  - Early diagnosis of functional damage in patients with glaucoma.

PMID- 9006433
TI  - Dominant optic atrophy, Kjer type. Linkage analysis and clinical features in a
      large British pedigree.
AB  - OBJECTIVES: To perform DNA linkage studies in an extensive 5-generation British
      pedigree with dominant optic atrophy and to validate the efficacy of domiciliary
      screening for affected members. METHODS: Family members received a domiciliary
      examination based on corrected visual acuity, color vision, visual field defects,
      and optic disc appearance; DNA linkage analysis was performed using 7
      microsatellite markers on 3q27-qter. RESULTS: Based on the results of the
      ophthalmic examination, 15 members could be classified as definitely affected, 1
      probably affected, and 25 unaffected. Two-point linkage analysis gave significant
      maximum lod scores at theta [corrected] = 0.00, with the markers D3S3669,
      D3S3590, and D3S3642. A haplotype segregating with the disease was identified in
      affected individuals, including the probably affected subject. Informative
      meioses defined the disease interval between markers D3S1601 and D3S1265.
      CONCLUSIONS: Domiciliary screening was effective in identifying all 16 affected
      members of a British family with dominant optic atrophy. The typical clinical
      features were present. The location of the OPA1 gene in this new British family
      seems to be in the 3q27-28 region and is the same as that reported in Danish,
      Cuban, and French families, suggesting no genetic heterogeneity in this disorder.

PMID- 9006437
TI  - Genomic mapping of Kjer Dominant Optic Atrophy.

PMID- 9006438
TI  - Osseous metaplasia in a preretinal membrane.
AB  - A highly myopic patient had surgery for retinal detachment in both eyes. After 3
      procedures, the left eye developed phthisis bulbi. After multiple procedures, the
      right eye underwent a vitrectomy for proliferative vitreoretinopathy. A plaque of
      preretinal tissue was removed. We found bone on pathologic examination. The
      retina remains attached, and visual acuity is 20/200. Ultrasonography showed
      additional evidence of calcification of both eyes, presumably metaplastic bone.

PMID- 9006439
TI  - A contact lens. 1888.

PMID- 9006440
TI  - Mullerian mixed tumor metastatic to the iris and ciliary body.

PMID- 9006441
TI  - Subperiosteal orbital hemorrhage from retrobulbar injection resulting in
      blindness.

PMID- 9006442
TI  - Two shielded 'bullet' probes for panoramic endoillumination.
AB  - Panoramic viewing during vitrectomy offers significant advantages over
      conventional viewing in many cases and is being used with increasing frequency.
      Two endoillumination probes that reduce the glare occurring with use of the
      existing panoramic endoillumination probes were developed. They allow easier
      viewing of the fundus in eyes with poor media and improve the visualization of
      the vitreous fibers adjacent to the probe in eyes with clear media. One probe is
      used for endoillumination alone, and the other has a pick to be used for bimanual
      dissection. The two probes have been used in more than 100 vitrectomies for
      various indications, and they give excellent illumination with reduced glare.

PMID- 9006443
TI  - Thrombotic thrombocytopenic purpura associated with purtscher retinopathy.

PMID- 9006444
TI  - Spontaneous resolution of a full-thickness macular hole with good visual acuity.

PMID- 9006445
TI  - A tactical response to the RAND Study.

PMID- 9006446
TI  - Evaluation of patients with retinitis pigmentosa receiving electric stimulation,
      ozonated blood, and ocular surgery in Cuba.

PMID- 9006447
TI  - Metastatic choroidal melanoma to the contralateral orbit 40 years after
      enucleation.

PMID- 9006448
TI  - Patient-physician covenant. The Ethics Committee of the American Academy of
      Ophthalmology.

PMID- 9006449
TI  - Advising patients with genital herpes.

PMID- 9006451
TI  - Setting priorities New Zealand-style.

PMID- 9006452
TI  - Hypoplastic left heart syndrome.

PMID- 9006453
TI  - "I've just been bitten by a dog".

PMID- 9006454
TI  - Meeting the information needs of health workers in developing countries.

PMID- 9006456
TI  - "Drive by" mastectomies to be banned.

PMID- 9006455
TI  - Doctors penalised for prescribing cannabis.

PMID- 9006457
TI  - Second Australian dies under euthanasia act.

PMID- 9006458
TI  - France faces first tobacco lawsuits.

PMID- 9006461
TI  - Dutch plan to tackle waiting lists.

PMID- 9006459
TI  - Chinese clamp down on blood products.

PMID- 9006462
TI  - Stable HIV rates hide worrying trends.

PMID- 9006463
TI  - AMA cautions on alternative therapies.

PMID- 9006464
TI  - Gulf War research given go ahead.

PMID- 9006465
TI  - A surgeon becomes overseer of Scotland's health.

PMID- 9006466
TI  - Are short normal children at a disadvantage? The Wessex growth study.
AB  - OBJECTIVE: To examine whether short stature through childhood represents a
      disadvantage at around 12 years. DESIGN: Longitudinal non-intervention study of
      the physical and psychological development of children recruited from the
      community in 1986-7 after entry into primary school at age 5-6 years; this is the
      second psychometric assessment made in 1994-5 after entry into secondary school
      at age 11-13 years. SETTING: Southampton and Winchester health districts.
      SUBJECTS: 106 short normal children (< 3rd centile for height when recruited) and
      119 controls of average stature (10th-90th centile). MAIN OUTCOME MEASURES:
      Psychometric measures of cognitive development, self concept development,
      behaviour, and locus of control. RESULTS: The short children did not differ
      significantly from the control children on measures of self esteem (19.4 v 20.2),
      self perception (104.2 v 102.4), parents' perception (46.9 v 47.0), or behaviour
      (6.8 v 5.3). The short children achieved significantly lower scores on measures
      of intelligence quotient (IQ) (102.6 v 108.6; P < 0.005), reading attainment
      (44.3 v 47.9; P < 0.002), and basic number skills (40.2 v 43.5; P < 0.003) and
      displayed less internalisation of control (16.6 v 14.3; P < 0.001) and less
      satisfaction with their height (P < 0.0001). More short than control children,
      however, came from working class homes (P < 0.05). Social class was a better
      predictor than height of all measures except that of body satisfaction.
      Attainment scores were predicted by class and IQ together rather than by height.
      Height accounted for some of the variance in IQ and locus of control scores.
      CONCLUSIONS: These results provide only limited support for the hypothesis that
      short children are disadvantaged, at least up until 11-13 years old. Social class
      seems to have more influence than height on children's psychological development.

PMID- 9006467
TI  - Case-control study of leukaemia among young people near La Hague nuclear
      reprocessing plant: the environmental hypothesis revisited.
AB  - OBJECTIVE: To investigate the association between childhood leukaemia and
      established risk factors or other factors related to La Hague nuclear waste
      reprocessing plant. DESIGN: Case-control study. SETTING: Area within a 35 km
      radius of La Hague, Normandy, France. SUBJECTS: Twenty seven cases of leukaemia
      diagnosed during the period 1978-93 in people aged under 25 years and 192
      controls matched for sex, age, place of birth, and residence at time of
      diagnosis. MAIN OUTCOME MEASURES: Antenatal and postnatal exposure to x rays and
      viral infections, occupational exposure of parents (particularly ionising
      radiation), living conditions, lifestyle of parents and children. RESULTS:
      Increased trends were found for use of local beaches by mothers and children (P <
      or = 0.01); relative risks 2.87 (95% confidence intervals 1.05 to 8.72) and 4.49
      (1.52 to 15.23) when categories were aggregated in two levels (more or less than
      once a month). Consumption of local fish and shellfish also showed an increased
      trend (P 0.01); relative risk 2.66 (0.91 to 9.51) when categories were grouped in
      two levels (more or less than once a week). A relative risk of 1.18 a year (1.03
      to 1.42) was observed for length of residence in a granite-built house or in a
      granitic area. No association was shown with occupational radiation exposure in
      parents. CONCLUSIONS: There is some convincing evidence in childhood leukaemia of
      a causal role for environmental radiation exposure from recreational activities
      on beaches. New methods for identifying the environmental pathways, focusing on
      marine ecosystems, are warranted.

PMID- 9006468
TI  - Changing prognosis for babies of less than 28 weeks' gestation in the north of
      England between 1983 and 1994. Northern Neonatal Network.
AB  - OBJECTIVE: To investigate the changing prognosis for babies of less than 28
      weeks' gestation. DESIGN: A prospective, collaborative, population based survey.
      SETTING: The former Northern Regional Health Authority. SUBJECTS: All the births
      between 1983 and 1994 at 22 to 27 completed weeks' gestation to women normally
      resident in the region. MAIN OUTCOME MEASURES: Miscarriage, stillbirth, death in
      the first year of life, and disability in survivors. RESULTS: There were 479070
      registered births in the study period. No baby of 22 weeks' gestation survived;
      only eight (4%) of the 197 babies of 23 weeks who were alive at the onset of
      labour survived for a year-a proportion that did not change during the study
      period. Survival among other babies of less than 28 weeks improved progressively
      between 1983-6 and 1991-4, but administration of artificial surfactant to babies
      requiring ventilation from mid-1990 was associated with further improvement in
      survival only in those over 25 weeks' gestation. Babies of 24 weeks required
      three times as much high dependency care per survivor as babies of 27 weeks (76 v
      26 days). The rate of severe disability in the one year survivors of less than 26
      weeks' gestation (30/123; 24%) was similar to that seen in the sampled survivors
      of 26 and 27 weeks (29/108; 27%); the proportion disabled did not change
      significantly during the study period. All the children born in 1983, 1987, and
      1991 were later reassessed in greater detail: 10% (13/136) seemed destined for a
      continuing life of total dependency. CONCLUSIONS: Gestation, if accurately
      assessed, can give a woman facing very preterm delivery a clear indication of the
      prognosis for her baby and help her judge the appropriateness of accepting
      obstetric intervention and sustained perinatal support.

PMID- 9006469
TI  - Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic
      ward studies.
AB  - OBJECTIVE: To determine the quantitative importance of dietary fatty acids and
      dietary cholesterol to blood concentrations of total, low density lipoprotein,
      and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward
      studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary
      experiments (median duration 1 month) among 129 groups of individuals. RESULTS:
      Isocaloric replacement of saturated fats by complex carbohydrates for 10% of
      dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03)
      mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l.
      Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of
      dietary calories resulted in total cholesterol falling by a further 0.13 (0.02)
      mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l.
      Similar replacement of carbohydrates by monounsaturated fats produced no
      significant effect on total or low density lipoprotein cholesterol. Avoiding 200
      mg/day dietary cholesterol further decreased blood total cholesterol by 0.13
      (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l.
      CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other
      fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol
      by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction
      being in low density lipoprotein cholesterol.

PMID- 9006470
TI  - Thermographic changes in keyboard operators with chronic forearm pain.

PMID- 9006471
TI  - Validation of a rapid whole blood test for diagnosing Helicobacter pylori
      infection.

PMID- 9006472
TI  - Feasibility and effects of nurse run clinics for patients with epilepsy in
      general practice: randomised controlled trial. Epilepsy Care Evaluation Group.
AB  - OBJECTIVE: To test the feasibility and effect of nurse run epilepsy clinics in
      primary care. DESIGN: A randomised controlled trial of nurse run clinics versus
      "usual care." SETTING: Six general practices in the South Thames region.
      SUBJECTS: 251 patients aged over 15 years who were taking anti-epileptic drugs or
      had a diagnosis of epilepsy and an attack in the past two years who met specified
      inclusion criteria and had responded to a questionnaire. MAIN OUTCOME MEASURES:
      Questionnaire responses and recording of key variables extracted from the
      clinical records before and after the intervention. RESULTS: 127 patients were
      randomised to a nurse run clinic, of whom 106 (83%) attended. The nurse wrote 28
      letters to the general practitioners suggesting changes in epilepsy management.
      For this intervention group compared with the usual care group there was a highly
      significant improvement in the level of advice recorded as having been given on
      drug compliance, adverse drug effects, driving, alcohol intake, and self help
      groups. CONCLUSIONS: Nurse run clinics for patients with epilepsy were feasible
      and well attended. Such clinics can significantly improve the level of advice and
      drug management recorded.

PMID- 9006473
TI  - Prevalence of arm movements in patients with coronary heart disease: case-control
      study.

PMID- 9006475
TI  - Molecular genetic approaches to understanding disease.
AB  - Molecular genetics has greatly increased the understanding of diseases in which
      there is a single gene defect such as cystic fibrosis. Discovering the gene
      responsible and its function not only helps determine the pathogenesis of the
      disease but also offers a possible treatment-gene therapy. Polygenic disorders
      such as diabetes may soon yield their secrets to the same approach. Animal models
      of genetic diseases are proving useful research tools, and transgenesis has made
      xenografting possible. Furthermore, antisense technology allows specific
      inhibition of undesirably overexpressed genes such as those driving unwanted
      vascular cell proliferation and restenosis after angioplasty. The completion of
      the human genome project should make the search for "disease" gene much quicker
      and will increase still further the importance of these gene based approaches
      toward diseases.

PMID- 9006474
TI  - Prophylaxis of venous thromboembolism.

PMID- 9006476
TI  - Man's best friend: life threatening sepsis after minor dog bite.

PMID- 9006477
TI  - The New Zealand priority criteria project. Part 1: Overview.
AB  - New Zealand restructured its health system in 1992 with the aim of achieving
      greater levels of assessment and accountability in the publicly funded health
      sector. A committee was established specifically to advise the minister of health
      on the kinds, and relative priorities, of health services that should be publicly
      funded. One of its projects has been to develop standardised sets of criteria to
      assess the extent of benefit expected from elective surgical procedures. These
      have been developed with the help of professional advisory groups using a
      modified Delphi technique to reach consensus. So far the committee has developed
      criteria for cataract surgery, coronary artery bypass grafting, hip and knee
      replacement, cholecystectomy, and tympanostomy tubes for otitis media with
      effusion. These criteria incorporate both clinical and social factors. Use of
      priority criteria to ensure consistency and transparency regarding patients'
      priority for surgery is required for access to a dedicated NZ$130m (pounds 57m;
      US$90m) pool of money, created to help eliminate surgical waiting lists and move
      to booking systems. The criteria will also be used in surgical outcome studies,
      currently in the planning phase.

PMID- 9006478
TI  - The New Zealand priority criteria project. Part 2: Coronary artery bypass graft
      surgery.
AB  - Priority criteria developed during a national project were used to conduct an
      audit of all 662 patients on waiting lists for coronary artery bypass surgery in
      New Zealand during spring 1996. Based on the observed distribution of priority
      scores, the cost of providing surgery to all patients down to various levels of
      priority was estimated. Descriptions incorporating life expectancy and quality of
      life implications of surgery were developed of the kinds of patients who would or
      would not receive surgery at each of several possible funding levels.
      Cardiologists and cardiac surgeons agreed that a threshold of 25 points was a
      reasonable clinical goal but to work with a threshold of 35, which can be
      sustained with current levels of funding. All agree that the gap between these
      clinically preferred and currently afforded thresholds is a subject for wider
      societal dialogue and decision. The ability to measure the size of the gap
      between clinical desirability and financial sustainability provides a new
      transparency to the problem of healthcare resource allocation.

PMID- 9006479
TI  - Can the NHS cope in future?
AB  - Four potential pressures are likely to determine whether the NHS will be able to
      cope in future: the change in population structure, changes in level of
      morbidity, introduction of new technologies, and increasing expectations of
      patients and NHS providers. New technology and changes in expectations are likely
      to have the biggest effect and are also the most difficult to quantify.
      Nevertheless, these pressures are to some extent amenable to control. If the
      growth in funding continues as it has in the past there is no convincing evidence
      that the NHS will not continue to cope.

PMID- 9006480
TI  - Widow's attempt to use her dead husband's sperm. Twin pregnancy resulted in case
      that was similar but in which consent was obtained.

PMID- 9006481
TI  - Widow's attempt to use her dead husband's sperm. Widow is a victim of "corporate
      tyranny".

PMID- 9006482
TI  - Serum cholesterol concentration and postpartum depression. Oestrogen may have
      been a confounder.

PMID- 9006484
TI  - Fifth of e antigen negative carriers of hepatitis B virus should not perform
      exposure prone procedures.

PMID- 9006485
TI  - Resuscitation witnessed by relatives. Has proved acceptable to doctors in
      paediatric cases.

PMID- 9006483
TI  - Serum cholesterol concentration and postpartum depression. Authors should read
      the literature that they cite.

PMID- 9006486
TI  - Resuscitation witnessed by relatives. Might lead to a complaint for breach of
      confidentiality.

PMID- 9006487
TI  - Insulin infusion in diabetic patients with acute myocardial infarction. Effective
      components of care and patients who might benefit must be determined.

PMID- 9006488
TI  - Insulin infusion in diabetic patients with acute myocardial infarction. Insulin
      should be continued for 12 months after acute event.

PMID- 9006489
TI  - Disagreements still exist over the chronic fatigue syndrome.

PMID- 9006490
TI  - Treating dysentery with metronidazole in Pakistan.

PMID- 9006491
TI  - Measurement error. A constant within subject standard deviation cannot be assumed
      a priori.

PMID- 9006492
TI  - Measurement error. Measurement error is that which we have not yet explained.

PMID- 9006493
TI  - Dietary habits and mortality in vegetarians and health conscious people. Several
      uncertainties still exist.

PMID- 9006494
TI  - Dietary habits and mortality in vegetarians and health conscious people. Weight
      cannot be interpreted without information on height.

PMID- 9006495
TI  - Safeguards are needed for new proposals for primary care.

PMID- 9006496
TI  - Information shared in mentoring must remain confidential.

PMID- 9006497
TI  - Critical pathways for head and neck surgery. Development and implementation.
AB  - OBJECTIVE: To design, implement, and study the effectiveness of 4 new critical
      pathways relevant to head and neck oncological care. DESIGN: Before-after trial.
      SETTING: Tertiary referral academic institution. PATIENTS: Sixty-eight patients
      admitted for head and neck oncological surgery or chemotherapy from December 1,
      1995, through May 31, 1996; 30 patients with similar diagnoses and who underwent
      surgical procedures from December 1, 1994, to December 1, 1995, who served as
      historical controls. INTERVENTIONS: Implementation of 4 critical pathways:
      chemotherapy, clean head and neck surgery, clean contaminated head and neck
      surgery, clean contaminated head and neck surgery with reconstructive flap. MAIN
      OUTCOME MEASURES: Length of stay, cost of hospitalization, and variance tracking
      (deviations from established standards). RESULTS: The length of stay for the
      clean contaminated group without flap reconstruction decreased by 1.5 days, and
      costs decreased by $7407 per patient (P < .05, Student t test). The length of
      stay decreased 1.6 days in the clean contaminated group with flap reconstruction,
      and costs decreased $9845 per patient (P < .05, Student t test). Nine patients
      (13%) experienced a prolonged length of stay while on a critical pathway.
      CONCLUSIONS: Implementation of critical pathways has resulted in a decreased
      overall length of stay and cost of hospitalization. It has also allowed for
      better coordination and documentation of patient care, while the tracking of
      variances has simplified problem identification and correction.

PMID- 9006498
TI  - Endovascular management of hemorrhage in patients with head and neck cancer.
AB  - OBJECTIVE: To present selective endovascular embolization as a therapeutic
      alternative to surgical ligation in the management of hemorrhage in patients with
      head and neck squamous cell carcinoma. DESIGN: Retrospective chart review of
      patients with head and neck cancer and significant hemorrhage who were treated
      with selective endovascular embolization. SETTING: A university medical center.
      PATIENTS: A total of 12 patients, aged 26 to 72 years, with 13 episodes of
      hemorrhage were treated at Oregon Health Sciences University, Portland, between
      November 1991 and January 1996. INTERVENTION: All patients underwent angiography
      with selective endovascular embolization at the interventional radiology suite
      using a combination of endovascular balloons, platinum coils, and microparticles.
      OUTCOME MEASURES: All charts were reviewed for diagnosis, treatment, factors that
      may have contributed to hemorrhage, bleeding site, therapeutic measures, control
      of hemorrhage, postembolization course, complications, and number of hospital
      days. RESULTS: The cause of the bleeding was tumor in 5 patients,
      pharyngocutaneous fistula in 4 patients, radiation necrosis in 3 patients, and
      postoperative complication in 1 patient. Bleeding arose from the common carotid
      artery in 4 patients, external carotid artery and its branches in 8 patients, and
      internal jugular vein in 1 patient. Hemorrhage was successfully controlled in all
      patients; a permanent left-sided hemiplegia and facial weakness developed in 1
      patient. There were no recurrences of hemorrhage. All patients were discharged
      from the hospital. CONCLUSION: Angiography with selective embolization is a safe
      and effective alternative to surgical ligation for control of hemorrhage in
      patients with squamous cell carcinoma of the head and neck.

PMID- 9006499
TI  - A new immunocompetent murine model for oral cancer.
AB  - OBJECTIVE: To develop and characterize a new immunocompetent murine model that
      attempts to parallel the clinical and biological nature of head and neck cancer.
      DESIGN: The growth rate and histologic characteristics of the SCC VII/SF cell
      line were initially determined in tissue culture experiments. Animal experiments
      were subsequently performed on C3H/HeJ mice. Using direct injection, 5 x 10(5)
      SCC VII/SF cells were delivered to the floor of the mouth of each animal. Animals
      were killed after 1, 2, and 3 weeks, and tumor growth, invasion, and regional and
      distant metastases were evaluated. RESULTS: Squamous cell carcinomas that could
      be palpated and measured externally were identified in the floor of the mouth of
      C3H/HeJ mice after 5 to 7 days. Local invasion into the mylohyoid musculature and
      mandible was present. Cervical lymph node and pulmonary metastases were
      identified between 2 and 3 weeks. CONCLUSIONS: This study introduces a new oral
      cancer animal model that shows initial locoregional tumor invasion, direct
      extension into the neck, early cervical metastases, and pulmonary metastases.
      These clinical and histopathologic attributes reflect the biological behavior and
      tumor progression seen in human oral cancer and therefore provide a model for
      clinically applicable research for primary and metastatic head and neck cancer.

PMID- 9006500
TI  - Generation of therapeutic T cells from draining lymph nodes in a murine model of
      head and neck squamous cell carcinoma.
AB  - OBJECTIVES: To study immunotherapy for advanced head and neck squamous cell
      carcinoma using AT-84, a spontaneously arising murine tumor. We examined the
      draining lymph nodes (DLNs) for generation of potential therapeutic lymphocytes
      in head and neck squamous cell carcinoma. DESIGN: Experimental randomized control
      trial. INTERVENTION: Therapeutic T cells from DLNs were generated by the
      sequential activation of the in vivo-primed DLN cells with 2C11, and anti-CD3
      antibody, and interleukin-2 (IL-2). Immunotherapy of mice bearing lung metastases
      was carried out in various experiments with low-dose systemic IL-2 and activated
      DLN cells. Using a 4-hour radioactive chromium Cr 51 release assay, in vitro
      cytotoxicity of these cells also was examined. RESULTS: Mice immunized with this
      tumor failed to reject the growth of a subsequent challenge with the tumor.
      Immunotherapy with low-dose systemic IL-2 resulted in a mean reduction of 79% in
      the number of lung metastases. Adoptive immunotherapy with activated DLN cells
      was effective in all experiments, with a mean reduction of 59% in the number of
      metastases in immunodeficient mice. However, DLN cells were not directly
      cytotoxic to the tumor cells in in vitro assays, unlike control lymphokine
      activated killer cells. CONCLUSIONS: AT-84 is a nonimmunogenic tumor similar to
      many human malignant neoplasms, making this a suitable model for immunotherapy.
      Low-dose systemic IL-2 was effective in reduction of established metastasis in
      this model. Activated DLN cells show reproducible in vivo therapeutic efficacy
      despite lack of in vitro cytotoxicity. Use of DLN cells as sources of therapeutic
      T cells in patients with head and neck squamous cell carcinoma deserves
      exploration because they are readily obtainable and because conventional
      treatment is of limited benefit.

PMID- 9006501
TI  - Successful treatment of esthesioneuroblastoma and neuroendocrine carcinoma with
      combined chemotherapy and proton radiation. Results in 9 cases.
AB  - OBJECTIVE: To study the efficacy of a newly designed treatment strategy for
      esthesioneuroblastoma and neuroendocrine carcinoma of the paranasal sinuses.
      DESIGN AND SETTING: Nonrandomized prospective study of a case series in a
      tertiary referral center. PATIENTS: Nine consecutive patients with newly
      diagnosed esthesioneuroblastoma or neuroendocrine carcinoma of the paranasal
      sinuses from June 1992 to October 1995 underwent this treatment protocol.
      INTERVENTIONS: After histological diagnosis and detailed imaging, 2 cycles of
      cisplatin and etoposide chemotherapy were instituted. Chemotherapy responders
      were treated with combined photon and stereotaxic fractionated proton radiation
      therapy totaling approximately 68 Gy to the primary site, whereas poor responders
      were treated with surgical resection followed by postoperative radiation. In both
      cases, therapy was then concluded with 2 additional cycles of cisplatin and
      etoposide chemotherapy. MAIN OUTCOMES MEASURES: Response to therapy, survival,
      disease-free survival, and complications of therapy were examined. RESULTS: Nine
      patients with a median Dulguerov T stage of T3 (range, T2 to T4) completed the
      treatment protocol, with mean follow-up after diagnosis of 20.5 months. Eight of
      9 patients exhibited a dramatic response to therapy with remission of their
      tumor, and resection was not required. One patient failed to respond to induction
      chemotherapy and received surgical therapy to be followed by postoperative
      radiotherapy. There have been no recurrences (mean disease-free interval of 14.0
      months). Complications were limited and generally transient. CONCLUSIONS: The use
      of combined cisplatin and etoposide chemotherapy with proton radiation has
      demonstrated initial success in treatment of these tumors. Dramatic response from
      chemotherapy is possible even in bulky or unresectable disease. This protocol has
      an acceptable complication rate and conveys less morbidity than craniofacial
      resection and conventional radiotherapy. Further follow-up will be required to
      determine the long-term success rate of this therapeutic protocol.

PMID- 9006502
TI  - The role of glucocorticoids in endotoxin-mediated otitis media with effusion.
AB  - OBJECTIVE: To understand the actions of glucocorticoids on the development and
      progression of endotoxin-mediated otitis media with effusion. METHODS AND DESIGN:
      The middle ears of 20 Sprague-Dawley rats were exposed to 35 microL of either 300
      mOsm Krebs-Ringer solution (control; n = 5) or lipopolysaccharide, 1 mg/mL,
      dissolved in Krebs-Ringer solution (n = 15). Among the group that received
      lipopolysaccharide, 10 rats were randomly selected to receive dexamethasone (1
      mg/kg intramuscularly), either 2 hours (n = 5) or 24 hours (n = 5) before the
      introduction of lipopolysaccharide. Middle ear fluid was sampled after 2, 4, and
      6 hours of exposure. OUTCOME MEASURES: Middle ear fluid volume and albumin
      content were determined as measures of vascular extravasation. Histological
      sections of the middle ear mucosa were used to quantify the degree of leukocyte
      exudation. Data were analyzed by 1- or 2-way analysis of variance with the
      significance level set at P < .05. RESULTS: Lipopolysaccharide exposure caused a
      significant increase in the mean +/- SEM middle ear fluid volume from 29.9 +/-
      0.99 to 45.8 +/- 1.4 microL between the 2- and 6-hour samplings.
      Lipopolysaccharide exposure caused a significant increase in the albumin content
      of middle ear fluid from 70.1 +/- 19.2 to 271.0 +/- 93.1 micrograms between the 2
      and 6-hour samplings. Both increases were significant compared with controls.
      Lipopolysaccharide also caused a significant increase in leukocytes localized to
      the middle ear mucosa. Pretreatment of animals with dexamethasone for either 2 or
      24 hours inhibited the lipopolysaccharide-induced changes. There were no
      differences between 2- and 24-hour pretreatment with dexamethasone. CONCLUSIONS:
      Dexamethasone inhibits the development of endotoxin-induced otitis media with
      effusion.

PMID- 9006504
TI  - Direct hypoglossal nerve stimulation in obstructive sleep apnea.
AB  - OBJECTIVES: To determine the motor responses resulting from direct electrical
      stimulation of the hypoglossal (HG) nerve and to correlate these responses to
      changes in upper airway patency during sleep. DESIGN: The motor effects of direct
      electrical stimulation of the main trunk of the HG nerve and the branch that
      supplies the genioglossus muscle during anesthesia and wakefulness were assessed
      visually. Responses in airflow during sleep to HG nerve stimulation were assessed
      with standard polysomnographic techniques. SETTING: University medical center.
      PATIENTS: Fifteen patients undergoing a surgical procedure that involved the neck
      that exposed the HG nerve and 5 volunteer patients with obstructive sleep apnea
      constituted the study population. INTERVENTIONS: The main trunk (n = 3) and
      genioglossus branch (n = 2) of the HG nerve were stimulated electrically with a
      half-cuff tripolar electrode. RESULTS: Stimulation of the branch of the HG nerve
      that innervates the genioglossus muscle caused protrusion and contralateral
      deviation of the tongue. Stimulation of the main trunk of the HG nerve caused
      slight ipsilateral deviation and retrusion of the tongue. The arousal threshold
      for stimulation exceeded the motor recruitment threshold by 0.8 +/- 0.4 V.
      Inspiratory airflow increased in all patients by 184.5 +/- 61.7 mL/s (mean +/-
      SD; P = .02, analysis of variance) with stimulation. CONCLUSION: Direct HG nerve
      stimulation below the arousal threshold can improve airflow in patients with
      obstructive sleep apnea.

PMID- 9006505
TI  - External auditory canal cholesteatoma.
AB  - A cholesteatoma originating in the external auditory canal is a rare finding. We
      report 2 cases illustrating its typical localization in the inferior part of the
      auditory canal and its marked osteolytic character. The extension of such a
      cholesteatoma in the depth of the temporal bone is often larger than suggested by
      clinical examination. Since the purpose of treatment is to achieve the complete
      eradication of the epidermic matrix, surgical treatment is required in most
      cases. We discuss herein the follow-up strategies, keeping in mind that local
      recurrence and bilateral disease are not uncommon.

PMID- 9006503
TI  - Herpes simplex virus antibodies in the perilymph of patients with Meniere
      disease.
AB  - OBJECTIVE: To evaluate the presence of IgG antibodies directed to herpes simplex
      virus (HSV) in the perilymph of patients with Meniere disease. DESIGN: Antibodies
      to HSV, Epstein-Barr virus, cytomegalovirus, and measles virus were analyzed in
      serum and perilymph samples by enzyme-linked immunosorbent assay. Total IgG and
      albumin in serum and perilymph samples were measured by nephelometer analysis.
      The relation of specific antivirus IgG in the perilymph vs the serum was
      expressed as an index. PATIENTS: Perilymph and serum samples from 7 patients with
      long-standing, disabling Meniere disease were collected during therapeutic
      vestibulotomy. Perilymph and serum samples from 7 patients with otosclerosis and
      2 recipients of cochlear implants were used as controls. RESULTS: Compared with
      the corresponding serum sample, the perilymph from the patients with Meniere
      disease disclosed a higher level of specific anti-HSV IgG. An elevated level of
      specific anti-measles virus IgG in the perilymph was detected in patients with
      otosclerosis. Patients of all groups showed no variation of specific anti-Epstein
      Barr virus IgG and anti-cytomegalovirus IgG in the serum or in the perilymph.
      CONCLUSIONS: Our results show the presence of HSV IgG in the perilymph of
      patients with Meniere disease and support the hypothesis that HSV may play an
      important role in the etiopathogenesis of Meniere disease.

PMID- 9006506
TI  - Isolated submentoplasty. A limited approach to the aging neck.
AB  - OBJECTIVE: To evaluate the application of a limited submentoplasty for improving
      the aesthetics of the cervical region. DESIGN: Retrospective analysis. SETTING:
      Private facial plastic surgery practice. All procedures were performed at an
      ambulatory surgical facility on an outpatient basis. PATIENTS: Forty patients (36
      women and 4 men) ranging from 37 to 68 years of age with a mean age of 52 years.
      Surgical procedures were performed over a 4-year period and follow-up ranged from
      3 months to 3.5 years with a mean follow-up of 1.2 years. INTERVENTION: Isolated
      submentoplasty operations performed by the senior surgeon (F.M.K.) over a 4-year
      period. OUTCOME MEASURES: Aesthetic appearance of the neck as determined by
      comparison of preoperative and postoperative physical examinations and
      photographs, subjective patient responses, and chart reviews to determine
      complications. RESULTS: Eighty percent success rate and 10% complication rate,
      with these complications being minor and easily correctable. CONCLUSION: Isolated
      submentoplasty is a viable option for correction of cervical deformities in
      selected patients.

PMID- 9006507
TI  - Tumefactive cartilage proliferation after rhinoplasty. A newly reported
      complication.
AB  - OBJECTIVE: To describe and document the development of tumoral proliferation of
      cartilage in 4 patients after nasal surgery, a complication that, to our
      knowledge, has not been reported before. DESIGN: Similar postoperative nasal
      masses were excised from 4 patients who underwent rhinoplasty. Histopathologic
      evaluation was carried out to identify the nature of the lesions and to provide a
      basis for rational management of similar lesions subsequently encountered.
      SETTING: Academic tertiary referral center. PARTICIPANTS: Four healthy patients
      (3 women and 1 man) ranging in age from 21 to 49 years. Two of the patients
      underwent routine rhinoplasty with resection of cephalic margins of alar
      cartilages, and 2 underwent augmentation procedures with implantation of
      auricular cartilage. INTERVENTION: Discrete firm masses were excised from each
      patient's nose approximately 1 year after the most recent rhinoplastic procedure
      was performed. Histological evaluation was carried out on each specimen. RESULTS:
      All 4 masses were found to consist of tumefactive proliferation of cartilage.
      Clonal proliferation and mild nuclear atypia were observed. CONCLUSIONS: After
      rhinoplasty, progressive asymmetrical fullness in or adjacent to cartilaginous
      structures or graft material should suggest the possibility of tumefactive
      proliferation of cartilage and should be evaluated with surgical exploration. All
      areas of thickened cartilage should be excised completely, with immediate
      auricular cartilage reconstruction of resulting anatomical defects. Perichondrium
      should be completely removed from auricular cartilage implants in the nose, and
      mechanical injury to the graft should be minimized. We strongly caution against
      morsellizing dorsal cartilage implants for nasal reconstruction.

PMID- 9006508
TI  - Occult malformations of the skull base.
AB  - Occult malformations of the skull base are rare anomalies. They are often not
      detected until they give rise to complications such as meningitis or
      cerebrospinal fluid rhinorrhea. We used high-resolution computed tomography,
      fluorescein endoscopy, cisternography, magnetic resonance imaging, and duraplasty
      to diagnose occult malformations of the skull base in 4 patients. The four
      patients had had between 4 and 6 attacks of meningitis. Cerebrospinal fluid
      rhinorrhea was confirmed in 3 cases. The following occult malformations were
      found: (1) an encephalocele of the glabella/cribriform plate and a meningocele at
      the petrous bone apex, (2) a meningoencephalocele at the petrous bone apex, (3)
      dural lesions in the regions foramen rotundum/sphenoid sinus and frontal
      sinus/cribriform plate, and (4) a dural lesion of the sphenoid sinus. In patients
      presenting with recurrent meningitis, meningitis with isolation of upper airway
      pathogens, or cerebrospinal fluid rhinorrhea, modern diagnostic methods should be
      used to search for dural lesions. Diagnosis of an occult malformation makes it
      possible to perform the necessary surgical repair and thus prevent the further
      occurrence of potentially fatal episodes of meningitis.

PMID- 9006509
TI  - Blunt laryngotracheal trauma in children.
AB  - OBJECTIVES: To demonstrate the diverse causes and manifestations of blunt
      laryngotracheal trauma in children, and to recommend an appropriate treatment
      protocol for these patients. DESIGN: A retrospective review of the medical
      records of patients treated at a tertiary care children's hospital for blunt
      laryngotracheal trauma during the 12 years before March 1, 1995 was performed.
      Clinical signs and symptoms, mechanisms of injury, and the results of
      laryngoscopy were included. PATIENTS: The study included 23 patients ranging from
      2 1/2 to 18 1/2 years of age. The medical records of patients who had sustained
      an injury as a result of penetrating trauma, intubation, or foreign body were
      excluded. RESULTS: Four patients urgently required tracheotomies; 2 of these
      patients required subsequent reconstructive airway procedures. One child required
      a microlaryngoscopy with relocation of the arytenoid cartilage. The remaining 18
      patients were treated conservatively with continuous pulse oximetry, cool mist
      room air, and serial flexible fiberoptic laryngoscopy. The 18 patients were
      discharged from the hospital after 24 to 48 hours of observation without
      sequelae. CONCLUSIONS: The signs and symptoms of blunt laryngotracheal trauma in
      children are not always specific to the extent or type of injury. A prompt
      diagnosis and treatment plan are needed to prevent potentially catastrophic
      complications. Patients with obvious airway compromise require immediate
      intervention. Those without acute airway symptoms often can be treated
      conservatively, provided that flexible fiberoptic laryngoscopy confirms a safe
      airway.

PMID- 9006510
TI  - Assessment of tracheoesophageal speech in a tonal language. A prospective study.
AB  - BACKGROUND: Tracheoesophageal puncture followed by insertion of a voice
      prosthesis is an increasingly popular method for voice rehabilitation after total
      laryngectomy. OBJECTIVE: To perform a functional assessment of voice produced by
      means of the Blom-Singer valve in a tonal language (Cantonese). DESIGN:
      Prospective study. SETTING: Hospital referral center. MAIN OUTCOME MEASURE: A 5
      point scoring scale was adopted for 15 test items of speech assessment grouped
      into 4 categories: phonatory skills, articulation, additional factors, and
      general judgment. The sum of the scores for the 15 items was the final speech
      score. The final speech score was rated as poor, satisfactory, or excellent if it
      was in the range of less than 30, 31 to 45, or 46 to 75, respectively. RESULTS:
      Forty-four users of the Blom-Singer valve who had undergone total laryngectomy
      and primary tracheoesophageal puncture were available for functional assessment.
      The final speech score was poor in 2 patients (5%), satisfactory in 4 (9%), and
      excellent in 38 (86%). CONCLUSION: Chinese patients can speak satisfactory tonal
      language with the Blom-Singer voice prosthesis.

PMID- 9006511
TI  - Brief bilateral vocal cord paralysis after insecticide poisoning. A new variant
      of toxicity syndrome.
AB  - We describe a new variant of life-threatening organophosphate toxicity syndrome
      that produces a brief bilateral vocal cord paralysis. There are 3 recognized
      types of toxicity syndrome: acute (instantaneous), intermediate (slightly
      delayed, i.e., hours to days), and delayed (weeks to months). Ingestions of large
      doses of insecticides lead to a cholinergic crisis and possible death (acute-type
      syndrome). Exposures to lower doses may cause the intermediate- or delayed-type
      syndrome. The intermediate-type syndrome is characterized by slightly delayed
      polyneuropathy and generalized weakness. Transient vocal cord paralysis has also
      been reported in association with other neurologically profound findings. The
      delayed-type syndrome can produce muscle weakness for months. Our patient, a 2
      year-old boy, was found eating a substance later found to be contaminated with
      insecticide. Within minutes, fever and somnolence developed, followed by
      progressive respiratory distress and stridor, without generalized weakness. The
      child's condition progressed to complete airway obstruction, and intubation was
      necessary. Emergency laryngoscopy and bronchoscopy were performed to rule out
      epiglottitis or a foreign body. Instead, a bilateral vocal cord paralysis was
      found. The paralysis lasted 2 days before completely resolving. Insecticide
      poisoning was suspected. We theorize that our patient manifested a combination of
      the acute-type syndrome, because of the immediacy of the onset of the symptoms
      (i.e., fever and somnolence), and the intermediate-type syndrome, because of the
      transient vocal cord paralysis. Because of the potential dangers involved, we
      wish to familiarize physicians concerning organophosphate poisoning; to alert the
      medical community to this variant of toxicity syndrome, which involves transient
      bilateral vocal cord paralysis; and to demonstrate the benefit of early
      otolaryngological consultation for the prevention and treatment of airway
      obstruction in patients with suspected organophosphate poisoning, be it from
      insecticides or poison gas.

PMID- 9006512
TI  - Congenital conductive hearing loss in the lacrimoauriculodentodigital syndrome.
AB  - An inherited middle ear anomaly that was causing hearing impairment in a 12-year
      old girl was treated successfully by a stapedotomy combined with a
      malleovestibulopexy. Cup-shaped ears, abnormal or absent thumbs, and skeletal
      deformities of the forearms were present in several members of 3 generations of a
      family. An autosomal dominant pattern of inheritance was recognized. These
      features are present in a number of previously described syndromes, but they
      correspond best with the lacrimoauriculodentodigital syndrome.

PMID- 9006513
TI  - Osseous craniofacial arteriovenous malformations in the pediatric population.
AB  - Osseous craniofacial arteriovenous malformations are rare and challenging
      entities. A 20-year retrospective review at our institutions identified 47 cases
      of craniofacial arteriovenous malformations, 3 of which were in children with
      extensive osseous facial structure involvement. Diagnostic evaluation included
      computed tomography, magnetic resonance imaging, and angiography. A 3-stage
      treatment protocol employed both transarterial embolization and direct
      intralesional puncture embolization followed by complete surgical resection. Mean
      intraperative blood loss was limited to 1000 mL. There were no complications
      during therapy. All 3 patients are without recurrence at 2- to 4-year follow-up.
      Osseous craniofacial arteriovenous malformations should be approached with
      multimodality therapy, incorporating interventional neuroradiologic and surgical
      management. Using the outlined protocol, these lesions can be treated safely and
      effectively.

PMID- 9006514
TI  - Maxillary malignant mesenchymoma and massive fibrous dysplasia.
AB  - This is the first report (to our knowledge) that describes a patient with massive
      polyostotic fibrous dysplasia involving the calvaria and facial skeleton that
      subsequently underwent transformation to a malignant mesenchymoma with elements
      of chondrosarcoma, osteosarcoma, and rhabdomyosarcoma arising in the maxilla.
      Malignant transformation occurred in the absence of prior radiation exposure,
      osteomyelitis, or known bony infarction. A review of the literature did not
      reveal any similar cases of massive fibrous dysplasia of the maxilla degenerating
      to multiple simultaneous malignant histotypes.

PMID- 9006515
TI  - Imaging quiz case 1. Neurosarcoidosis (NS).

PMID- 9006516
TI  - Imaging quiz case 2. Cherubism.

PMID- 9006517
TI  - The good, the bad, and the ugly.

PMID- 9006518
TI  - Transfacial surgical access in the treatment of angiofibroma.

PMID- 9006519
TI  - Combined modality treatment of advanced head and neck cancer.

PMID- 9006520
TI  - Overmedication in outpatient tonsillectomy.

PMID- 9006521
TI  - Middle turbinate stabilization.

PMID- 9006522
TI  - Resumption of menses in anorexia nervosa. New research findings and their
      clinical implications.

PMID- 9006523
TI  - Resumption of menses in anorexia nervosa.
AB  - OBJECTIVE: To determine factors associated with resumption of menses (ROM) in
      adolescents with anorexia nervosa. DESIGN: Cohort study with 2-year follow-up.
      SETTING: Tertiary care referral center. PATIENTS: Consecutive sample of 100
      adolescent girls with anorexia nervosa. INTERVENTIONS: Body weight, percent body
      fat, and luteinizing hormone, follicle-stimulating hormone, and estradiol levels
      were measured at baseline and every 3 months until ROM (defined as 2 or more
      consecutive spontaneous menstrual cycles). Treatment consisted of a combination
      of medical, nutritional, and psychiatric intervention aimed at weight gain and
      resolution of psychological conflicts. MAIN OUTCOME MEASURES: Body weight, body
      composition, and hormonal status at ROM. RESULTS: Menses resumed at a mean (+/
      SD) of 9.4 +/- 8.2 months after patients were initially seen and required a
      weight of 2.05 kg more than the weight at which menses were lost. Mean (+/-SD)
      percent of standard body weight at ROM was 91.6% +/- 9.1%, and 86% of patients
      resumed menses within 6 months of achieving this weight. At 1-year follow-up, 47
      (68%) of 69 patients had resumed menses and 22 (32%) remained amenorrheic. No
      significant differences were seen in body weight, body mass index, or percent
      body fat at follow-up in those who resumed menses by 1 year compared with those
      who had not. Subjects who remained amenorrheic at 1 year had lower levels of
      luteinizing hormone (P < .001) and follicle-stimulating hormone (P < .05) at
      baseline and lower levels of luteinizing hormone (P < .01) and estradiol (P <
      .001) at follow-up. At follow-up, a serum estradiol level of more than 110 pmol/L
      (30 pg/mL) was associated with ROM (relative risk, 4.6; 95% confidence interval,
      1.9-11.2). CONCLUSIONS: A weight approximately 90% of standard body weight was
      the average weight at which ROM occurred and is a reasonable treatment goal
      weight, because 86% of patients who achieved this goal resumed menses within 6
      months. Resumption of menses required restoration of hypothalamic-pituitary
      ovarian function, which did not depend on the amount of body fat. Serum estradiol
      levels at follow-up best assess ROM.

PMID- 9006524
TI  - The use of television in 2- to 8-year-old children and the attitude of parents
      about such use.
AB  - BACKGROUND: It has been recognized that uncontrolled use of television (TV) in
      childhood is potentially harmful. Few data about family habits regarding TV use
      are available. OBJECTIVE: To evaluate the quantitative-qualitative TV viewing
      habits of children and the relationship between the attitudes of parents about TV
      programs and TV use by their children. DESIGN: Descriptive study. SETTING:
      General pediatric community. PARTICIPANTS: A convenience sample. All the parents
      of the children attending the nursery school, kindergarten, and the first 2 years
      of elementary school in a neighborhood of Padova, a city in northern Italy. The
      parents of 156 children (95%) responded. RESULTS: Nine percent of the children
      viewed TV for more than 3 hours per day, and 50% of the children viewed TV for 1
      to 3 hours per day. A range of TV programs were viewed. Parents were involved in
      the TV use of their children; the most frequent way was by prohibiting some
      programs. The attitudinal profiles of the parents about the contents and the
      value of TV messages were notably associated with different kinds of TV use. A
      high score (ie, an optimistic judgment) on the attitudinal profile about the
      contents of TV programs was significantly associated with greater quantitative (P
      < .04), uncritical exposure (P < .05) of children to TV messages. A high score
      (ie, severe judgment) on the attitudinal profile regarding the values of TV
      programs was associated with qualitatively better exposure to TV (P < .05) and
      greater selectivity of programs watched (P < .05). In the parents, a critical
      attitude seemed to have a direct relationship with a higher social and
      educational level. CONCLUSIONS: This pilot study suggests that the attitude of
      parents about TV may influence the TV viewing habits of children. A broader study
      that accounts for this factor and other factors that influence TV use is
      necessary to better understand the reasons for the excessive exposure of children
      to TV.

PMID- 9006525
TI  - Score for neonatal acute physiology and phlebotomy blood loss predict erythrocyte
      transfusions in premature infants.
AB  - OBJECTIVE: To test the hypothesis that utilization of a previously described
      measure of acuity (ie, the score for neonatal acute physiology [SNAP]) during the
      first 7 postnatal days predicts which infants with a birth weight of 1500 g or
      less received erythrocyte transfusion during the initial hospitalization. DESIGN:
      Retrospective chart review. SETTING: A regional tertiary care newborn intensive
      care unit at the Arizona Health Sciences Center, University Medical Center,
      Tucson. MATERIALS: Medical records of premature infants (birth weight, < or =
      1500 g) who were admitted from October 1993 to January 1995. MAIN OUTCOME
      MEASURES: Occurrence or nonoccurrence of erythrocyte transfusion was determined
      in 47 infants who were compared for demographic information, phlebotomy blood
      loss, diagnoses, medications, and the SNAP at 0, 1, 2, and 7 days of life.
      RESULTS: Infants with a birth weight of 1500 g or less received a mean +/- SD of
      1.9 +/- 2.9 transfusions with 22 (47%) of the infants given transfusions Infants
      who were given transfusions vs those who were not given transfusions were of a
      lower mean +/- SD birth weight (971 +/- 238 g vs 1272 +/- 144 g; P < .001) and a
      lower gestational age (27.7 +/- 1.6 weeks vs 30.7 +/- 2.8 weeks; P < .001), and
      they had a greater mean phlebotomy blood loss (3.3 +/- 1.6 mL/kg per day vs 1.4
      +/- 0.5 mL/kg per day; P < .001) during the first postnatal week. The SNAP
      indexes in those who received transfusions were higher at 1, 2, and 7 days of
      life (P = .03, P = .001, and P < .001, respectively). Using stepwise logistic
      regression, phlebotomy blood loss and the SNAP at 7 days of life were significant
      predictors of the number of transfusions. The logistic model predicted which
      infants had been administered transfusions with 86% sensitivity and 88%
      specificity. CONCLUSIONS: The efficacy and cost-effectiveness of recombinant
      human erythropoietin therapy in premature infants remain under study. As earlier
      treatment with recombinant human erythropoietin may be more efficacious, early
      identification of which infants currently undergo transfusion may identify those
      who will receive the greatest benefit from recombinant human erythropoietin
      therapy. The SNAP distinguished those infants who were given transfusions from
      those who did not receive transfusions, even after adjusting for phlebotomy blood
      loss.

PMID- 9006526
TI  - Economic impact of pertussis.
AB  - OBJECTIVE: To assess the economic consequences of pertussis in Monroe County, New
      York (population, 713969), during a 6-year period (1989-1994). METHODS: Cases of
      pertussis were identified retrospectively by passive reporting and diagnosis
      based on culture, positive results of direct fluorescent antibody testing, or
      Centers for Disease Control and Prevention clinical criteria (cough for > 14 days
      otherwise unexplained or for > 7 days with paroxysms or whoop epidemiologically
      linked to a laboratory-confirmed case). One hundred seven (50%) of 216 subjects
      with identified cases of pertussis completed questionnaires and had medical
      records reviewed to ascertain the costs of illness, including physician office
      visits, laboratory tests, medications, hospitalization, emergency department
      visits, additional child care, and lost days from school (children) or from work
      (parents or adult cases). RESULTS: Ninety-three (87%) of the pertussis case
      occurred in children. The average duration of illness before diagnosis was 21.3
      days (range, 12-37 days). One hundred one patients (94%) saw a physician at least
      once; overall, the average number of visits per case was 3.2 (range, 1-15).
      Ninety-seven patients (91%) received at least 1 course of antibiotic therapy
      (average cost for all antibiotics, $95/case), and all took symptomatic treatment
      (average cost, $48/case). Fifteen patients (14%) required hospitalization;
      average cost per admission was $13425 (range, $1732-$69637). Thirty patients
      (28%) were seen in emergency departments; average cost was $202 (range, $69
      $289). Additional child care costs ranged from $12 to $2688. For 50 families, 1
      adult lost workdays because of illness or to provide child care for an average of
      8.3 days (range, 1-45 days). For 4 families, 2 adults lost an average of 44 days
      from work (range, 10-120 days). The cumulative number of lost workdays was 758 in
      association with the 107 cases of pertussis. The average full recovery time from
      illness was 72.9 days (range, 25-115 days). CONCLUSIONS: Total direct and
      indirect cost for 107 cases of pertussis in Monroe County was $381052. The
      economic burden of pertussis is substantial and encourages broader use of
      vaccination to prevent disease.

PMID- 9006527
TI  - Effect of education and legislation on bicycle helmet use in a multiracial
      population.
AB  - OBJECTIVE: To observe the effect of new legislation and a boroughwide bicycle
      helmet educational campaign on bicycle helmet use in a multiracial population.
      DESIGN: A prospective observational study. Observations were made at randomly
      selected sites in Queens (study group) and Brooklyn (control group), NY, in May
      1994, before a New York State law affecting both boroughs was enacted and before
      a bicycle helmet educational campaign was conducted in Queens. Variables observed
      included age, sex, race, and whether the child was wearing a bicycle helmet while
      riding. A bicycle helmet campaign was conducted in late May 1994. New York State
      bicycle helmet law was effected on June 1, 1994, requiring all children aged 1 to
      14 years to wear helmets while riding their bicycles. Follow-up observations were
      made at the same sites in July or August 1994. SETTING: Queens County, New York,
      which is the most racially diverse county in the United States, according to 1990
      census data. PARTICIPANTS: Cross-sectional observations of children aged 1 to 14
      years made at randomly selected sites. INTERVENTIONS: A boroughwide bicycle
      helmet educational campaign conducted in May 1994 in Queens. RESULTS: The overall
      use of helmets increased from 4.7% (13/276) to 13.9% (44/316) (P < .001) in the
      study group. Helmet use decreased from 5.6% (19/342) to 4.2% (13/312) (P = .10)
      in the control group during the same period. CONCLUSIONS: In a multiracial
      population, a statistically significant (P < .001) increase of helmet use was
      demonstrated after a campaign and distribution of educational material.
      Legislation alone is inadequate for ensuring increased bicycle helmet use.

PMID- 9006528
TI  - A study of 5-day cefdinir treatment for streptococcal pharyngitis in children.
      Cefdinir Pediatric Pharyngitis Study Group.
AB  - OBJECTIVE: To compare the safety and efficacy of a 5-day regimen of cefdinir with
      those a conventional 10-day regimen of penicillin V for the treatment of
      streptococcal pharyngitis in children. DESIGN: Investigator-blind, randomized
      controlled trial. SETTING: Primary care, ambulatory. PATIENTS: Children aged 1 to
      12 years with signs and symptoms of pharyngitis and a positive result on a rapid
      screening test for Streptococcus pyogenes (ie, a convenience sample). Four
      hundred eighty-two patients were enrolled in the study, and 440 were clinically
      and microbiologically evaluable. The most common reasons patients were
      nonevaluable were failure to return for specified visits and noncompliance with
      the administration of the medication; 2 patients receiving penicillin V
      discontinued use of the drug because of adverse events. INTERVENTION: Patients
      were randomized to receive either 7-mg/kg cefdinir, twice daily, for 5 days or 10
      mg/kg penicillin V potassium, 4 times daily, for 10 days. MAIN OUTCOME MEASURES:
      The eradication of S pyogenes and the clinical cure of the signs and symptoms of
      pharyngitis, both determined 5 to 10 days after the completion of therapy.
      RESULTS: Streptococcus pyogenes was eradicated in 201 (90%) of the 224 patients
      receiving cefdinir and 155 (72%) of the 216 patients receiving penicillin V (95%
      confidence interval [CI], 10.7%-25.1%; P < .001). The clinical cure rates were
      92% and 91% in the groups receiving cefdinir and penicillin V, respectively (95%
      CI, -4.5% to 6.1%; P = .80). Adverse events, regardless of the opinion of the
      investigator about their relationship to the study medication, occurred in 12.5%
      of the patients receiving cefdinir and 13.6% of the patients receiving penicillin
      V (P = .69). CONCLUSIONS: A 5-day regimen of cefdinir eradicated a higher
      proportion of S pyogenes than a 10-day regimen of penicillin V. No difference was
      noted between the regimens for clinical outcomes or adverse event rates.

PMID- 9006529
TI  - Reference data for head circumference-for-length in preterm low-birth-weight
      infants.
AB  - OBJECTIVE: To provide reference data for head circumference-for-length in preterm
      low-birth-weight infants that are independent of age, but extend for the ranges
      of head circumference (34-49 cm) and length (52.0-102.9 cm) values found from
      birth to 36 months of gestation-adjusted age. DESIGN: Measurements were made at 9
      ages in 867 preterm infants in the Infant Health Development Program, a
      randomized clinical trial that included various ethnic groups at 8 sites. At
      birth, two thirds of the infants weighed less than 2000 g, and one third weighed
      between 2000 and 2500 g. Measurements were taken at birth, at 40 weeks of
      postconceptional age, and at 4, 8, 12, 18, 24, 30, and 36 months of gestation
      adjusted age. A model fitted to the serial data for each infant was used to
      estimate head circumference and length from 36 weeks after conception to 36
      months of gestation-adjusted age. RESULTS: Tables and charts of means and SDs and
      selected percentiles for each sex were made. These tables and charts are for very
      low (< or = 1500 g) and low-birth-weight (1501-2500 g) infants by 3-cm intervals
      of length. CONCLUSION: These tables and charts should assist clinicians in
      evaluating and monitoring head circumference in preterm low-birth-weight infants
      by taking body length into account.

PMID- 9006530
TI  - Evaluation of a statewide bicycle helmet law via multiple measures of helmet use.
AB  - OBJECTIVES: To evaluate an Oregon law requiring bicyclists younger than 16 year
      to wear a helmet and to compare methods of measuring helmet use. DESIGN: Four
      prelaw and postlaw statewide helmet use surveys: (1) statewide observations, (2)
      middle school observations, (3) classroom self-report surveys, and (4) a
      statewide adult telephone survey. SETTING: Oregon. SUBJECTS: Statewide
      observations, 3313 child bicyclists at 13 sites; middle school observations, 995
      child bicyclists at 33 randomly selected middle schools; classroom self-report
      surveys, fourth, sixth, and eighth graders in 448 classrooms (ie, 8955 students)
      before the law was effected and 456 classrooms (ie, 9811 students) after the law
      was effected in 66 randomly selected schools; and statewide telephone survey,
      1219 randomly called parents of 1437 children younger than 16 years. MAIN OUTCOME
      MEASURES: Prelaw and postlaw helmet use and ownership and knowledge and opinion
      about the law. RESULTS: Observed helmet use among youth was 24.5% before the law
      was effected and 49.3% after the law was effected. School-observed use increased
      from 20.4% to 56.1%. Classroom survey self-reported "always" use of helmets
      increased from 14.7% to 39.4%; reported use on the day of the survey increased
      from 25.8% to 76.0%. Telephone survey-reported "always" helmet use increased from
      36.8% to 65.7%. Younger children and girls were more likely to use helmets. Most
      students (ie, 87.8%) and parents (ie, 95.4%) knew about the law; however, only
      42.6% of children thought the law was a good idea. CONCLUSIONS: We conclude that
      (1) the law increased helmet use; (2) although use estimates differ, all helmet
      surveys showed similar degrees of prelaw and postlaw change; and (3) half of
      child bicyclists are still not wearing helmets, indicating a need for additional
      promotion of helmet wearing. Laws seem to be an effective way to increase helmet
      use.

PMID- 9006532
TI  - Clothing drawstring entrapment in playground slides and school buses.
      Contributing factors and potential interventions.

PMID- 9006531
TI  - Relationship between cigarette smoking and health risk and problem behaviors
      among US adolescents.
AB  - OBJECTIVE: To examine whether sociodemographic factors and health risk and
      problem behaviors explain the prevalence of cigarette smoking among US
      adolescents. DESIGN: Probability survey. PARTICIPANTS: A nationally
      representative sample of US adolescents. MAIN OUTCOME MEASURES: Weighted
      prevalence, adjusted odds ratio (OR), and 95% confidence intervals (CIs) for
      current smoking status by health risk and problem behaviors. RESULTS: The
      prevalence of smoking was highest among adolescents who were white, older, and
      who had a high school education or lived in the Northeast. When we adjusted for
      sociodemographic factors and health risk and problem behaviors, smoking was
      associated with marijuana use (OR, 3.7; 95% CI, 2.7-5.1), binge drinking (OR,
      2.1; 95% CI, 1.6-2.8), and fighting (OR, 1.4; 95% CI, 1.1-1.7) among white
      adolescent males. Similar associations between each of these 3 behaviors and
      cigarette smoking were found among white adolescent females and African American
      and Hispanic adolescent males and females. Cigarette smoking was also associated
      with using smokeless tobacco, having multiple sexual partners, and not using
      bicycle helmets among white adolescent males and females, having multiple sexual
      partners among Hispanic adolescent females, and carrying weapons among Hispanic
      adolescent males. CONCLUSIONS: Marijuana use, binge drinking, and fighting are
      correlates of cigarette smoking among US adolescents. These associations, which
      vary by sex and race or ethnicity, suggest clustering to form a risk behavior
      syndrome.

PMID- 9006533
TI  - Pediatric residency as preparation for primary care practice.
AB  - OBJECTIVES: To assess the effectiveness of pediatric residency training as
      preparation for primary care and make recommendations for improving residency
      training. METHOD: Two surveys were sent to graduate of the pediatric residency at
      the University of Colorado from 1984 to 1991. The first survey requested
      information about practice patterns and ratings of preparedness in 45 areas
      important for primary care. The second survey requested ratings of importance for
      increasing training time in 25 areas judged as inadequate in the first survey.
      RESULTS: Of 147 surveys mailed, 103 graduates responded and rated themselves as
      less than adequately trained in 25 of 45 areas selected for relevance to primary
      care. Graduates of the primary care track rated themselves as significantly
      better trained than graduates of nonprimary care tracks in 10 of 45 areas;
      nonprimary care graduates had higher ratings in 2 of 45 areas. The second survey
      (completed by 70 of the 103 initial responders) indicated that the top 5 areas
      needing increased time in residency training were, in descending order,
      orthopedics, developmental and behavioral problems, learning disability,
      attention-deficit hyperactivity disorder, and school difficulty. Graduates of the
      primary care track rated themselves as adequately trained in developmental and
      behavioral problems and attention-deficit hyperactivity disorder, but they and
      nonprimary care graduates felt inadequately prepared in the other 3 areas.
      CONCLUSION: Implications of these results change with different content areas,
      suggesting the need to improve training for all residents in some areas and
      extending to all residents some of the curriculum already implemented in the
      primary care track.

PMID- 9006535
TI  - Radiological case of the month. Choroid plexus papilloma.

PMID- 9006536
TI  - Radiological case of the month. Mucocele of the sphenoid sinus.

PMID- 9006534
TI  - Lipoprotein and apolipoprotein differences in black and white girls. The National
      Heart, Lung, and Blood Institute Growth and Health Study.
AB  - OBJECTIVE: To define racial differences in lipoprotein and apolipoprotein levels
      in girls aged 9 to 10 years. DESIGN: Baseline analysis of a prospective cohort
      study. SETTING: Three clinical sites. SUBJECTS: A total of 1871 black and white
      girls, aged 9 to 10 years, with complete maturation data (pubic hair and areolar
      development and menarche) and an 8-hour fast before blood draw. MAIN OUTCOME
      MEASURES: Anthropometric measures and serum lipid, lipoprotein, and
      apolipoprotein levels. RESULTS: All analyses were adjusted for maturational
      differences between blacks and whites (areolar or pubic hair development and
      menarche). The mean body mass index was marginally higher in black girls than in
      white girls (18.9 vs 18.3 kg/m2; P = .002), while the sum of skinfolds (34.5 vs
      34.8 mm; P = .77) was equivalent. However, both body mass measures were skewed
      higher at the upper percentiles in black girls. The low-density lipoprotein
      cholesterol level was similar between black and white girls. Mean triglyceride
      values were higher in white girls than in black girls (0.92 vs 0.79 mmol/L [81 vs
      70 mg/dL]; P < .001); however, these differences were most pronounced in the
      upper percentiles. Conversely, mean high-density lipoprotein cholesterol and
      apolipoprotein A-I levels were higher in black girls than in white girls (1.44 vs
      1.37 mmol/L [56 vs 39 mg/dL] and 147 vs 138 mg/dL, respectively; both P < .001);
      and again the differences were most evident at the upper end of the
      distributions. CONCLUSIONS: Racial differences in the mean levels of
      triglycerides, high-density lipoprotein cholesterol, and body mass in girls in
      the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) at
      age 9 to 10 years were predominantly the result of differences observed at the
      upper end of the distributions. The reported black-white differences for mean
      high-density and low-density lipoprotein cholesterol and triglyceride levels in
      adult women are comparable to NGHS results. Distributional characteristics of
      these risk factors as well as trends in lipids, lipoproteins, and
      apolipoproteins, will be evaluated in an ongoing longitudinal assessment that
      covers the full maturational period.

PMID- 9006537
TI  - Picture of the month. Ectopic ureterocele prolapsing through the urethra.

PMID- 9006538
TI  - Pathological case of the month. Pseudoxanthoma elasticum.

PMID- 9006539
TI  - Bone mineralization and bone maturation in precocious puberty.

PMID- 9006540
TI  - Forensic examination of adolescent female genitalia: the Foley catheter
      technique.

PMID- 9006541
TI  - Chronic subungual hematomas: a presumed immunologic puzzle resolved with a
      diagnosis of child abuse.

PMID- 9006542
TI  - Epidemiology of shopping cart-related injuries to children.

PMID- 9006543
TI  - PALS course improves preparedness for pediatric emergencies.

PMID- 9006544
TI  - Reputed brain damage and 'serious' reactions from DTP vaccines.

PMID- 9006545
TI  - Anti-inflammatory therapy reduces wheezing after bronchiolitis.

PMID- 9006547
TI  - Characteristics of thoracic duct lymph in multiple organ dysfunction syndrome.
AB  - OBJECTIVE: To investigate the presence of endotoxin, bacteria, and potential
      humoral and cellular mediators in thoracic duct lymph and peripheral blood in
      patients with severe refractory multiple organ dysfunction. DESIGN: Convenience
      sample. SETTING: General intensive care unit of a university hospital. PATIENTS:
      Two men and 2 women were studied after a mean of 7.25 days (range, 6-9 days) of
      multiple organ dysfunction syndrome. The primary injury was thoracic in 1 patient
      and abdominal in 3 patients. INTERVENTION: The thoracic duct was cannulated with
      a 7F catheter and samples of lymph and peripheral blood were obtained. MAIN
      OUTCOME MEASURES: Simultaneous lymph and serum levels of lipopolysaccharide,
      tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6, and
      activation markers on T lymphocytes. RESULTS: Lipopolysaccharide and cytokine
      levels were low in lymph and serum, except for a mean lymph-to-serum ratio of
      53.4 for interleukin-1 beta. There was phenotypical evidence of intense
      polyclonal T-lymphocyte activation in both lymph and peripheral blood with
      increased lymph-to-peripheral blood ratios. Increased percentages in lymph of
      CD45RA + CD45RO + lymphocytes were observed. In 1 patient, Proteus mirabilis grew
      simultaneously in lymph, pancreatic necrosis fluid, and a central venous catheter
      tip. All simultaneous blood cultures were negative. CONCLUSIONS: Our results
      provide evidence of the participation of the gut-associated lymphatic tissue in
      the pathogenesis of the multiple organ dysfunction syndrome, suggesting that T
      cell activation and cytokine production occur at the gut level. Future studies
      are needed to confirm and extend our findings.

PMID- 9006546
TI  - Impaired endothelium-dependent relaxation of human hepatic arteries after
      preservation with the University of Wisconsin solution.
AB  - OBJECTIVE: To evaluate the effect of University of Wisconsin solution on
      endothelium-dependent relaxation and contraction of human hepatic arteries in
      vitro. DESIGN: Human hepatic arteries were harvested from 24 patients with
      hepatocellular carcinoma who had undergone hepatectomy. SETTING: A tertiary care
      center. INTERVENTIONS: Human hepatic arteries (n = 6 in each group) were
      harvested during resection for hepatocellular carcinoma. The arteries in group 1
      (i.e., the control group) were immediately studied without preservation. The
      arteries in group 2 were preserved in cold (4 degrees C) physiological solution
      for 1 hour, while the arteries in groups 3 and 4 were preserved in University of
      Wisconsin solution for 1 and 16 hours, respectively. Segments of control and
      preserved hepatic arteries with or without endothelium were then suspended in
      organ chambers to measure the isometric force. RESULTS: The relaxation of
      segments of the hepatic arteries with endothelium in response to acetylcholine
      and adenosine diphosphate was significantly (P < .05) greater than that of
      segments without endothelium. The maximal relaxation of hepatic arterial segments
      with endothelium in groups 3 and 4 in response to acetylcholine was notably
      different from that of segments in groups 1 and 2. The maximal relaxation of
      hepatic arterial segments with endothelium in groups 3 and 4 in response to
      adenosine diphosphate was notably different from that of segments in groups 1 and
      2. Perfusate hypoxia (mean +/- SD PO2, 30 +/- 5 mm Hg) caused the endothelium
      dependent contraction of the arteries (the median initial tension in groups 1, 2,
      3, and 4 was 251%, 233%, 276%, and 260%, respectively; P > .05). CONCLUSIONS: The
      endothelium-dependent relaxation of human hepatic arteries in response to
      acetylcholine and adenosine diphosphate was notably attenuated by University of
      Wisconsin solution. The impaired endothelium-dependent relaxation by University
      of Wisconsin solution and the prominent endothelium-dependent contraction of
      human hepatic arteries would favor vasospasm and thrombosis after hepatic
      transplantation.

PMID- 9006548
TI  - Extracorporeal shock wave lithotripsy for the treatment of renal stones.
      Treatment policy is as important for success as type of lithotriptor and patient
      selection.
AB  - OBJECTIVE: To compare the efficiency of different machines for extracorporeal
      shock wave lithotripsy (ESWL) of renal stones and to analyze treatment strategies
      and stone characteristics as determinants of treatment failure. DESIGN:
      Prospective cohort study. SETTING: Nationwide study in Sweden. All 11 hospitals
      in Sweden using 1 of 7 lithotriptors in 1991 were included. PATIENTS: The study
      cohort comprised 1171 (97.6%) of the 1200 patients in Sweden who underwent ESWL
      for the first time because of renal stones between February 18, 1991, and
      December 31, 1991. MAIN OUTCOME MEASURE: Treatment failure, defined as 1 or more
      residual renal stone fragments larger than 4 mm 1 of 3 months after the end of
      treatment, was analyzed after ESWL monotherapy and after ESWL plus auxiliary
      treatment using a multivariate analysis. RESULTS: Treatment failure varied by
      center from 12% to 48% (mean, 24%) after ESWL monotherapy and from 4% to 40%
      (mean, 18%) after ESWL plus auxiliary procedures. After adjusting for differences
      in the patient mix, the risk of treatment failure, measured as the odds ratio,
      varied by center almost 7-fold after ESWL monotherapy and 20-fold after ESWL plus
      auxiliary treatment. Substantial differences also existed for the same equipment
      used at different centers. The risk of treatment failure increased rapidly for
      renal stones larger than 15 mm, and it was at least 2-fold higher in patients who
      had multiple stones or a cavity. CONCLUSIONS: When ESWL is used for the treatment
      of renal stones, the treatment policy has as great an effect on the success rate
      and need for auxiliary treatment as optimal equipment and proper patient
      selection. Meaningful comparisons of different lithotriptors require multivariate
      analyses with adjustment for patient selection.

PMID- 9006549
TI  - Cryosurgery of breast cancer.
AB  - OBJECTIVE: To determine the feasibility and efficacy of cryosurgery of breast
      cancer. DESIGN: In phase 1, carcinogen-induced mammary adenocarcinomas in 13
      Sprague-Dawley rats were treated by cryosurgery and were then examined for
      histopathologic change. In phase 2, transplantable mammary adenocarcinomas in 50
      DBA/IJ mice were treated by cryosurgery to determine the effect of varying tumor
      temperatures, and duration and number of freeze-thaw cycles on tumor viability.
      In phase 3, 2- to 3-cm ultrasound-monitored cryolesions were formed in the
      breasts of 4 dogs and 4 sheep. These animals were followed up for procedure
      related complications; the histopathologic necrosis of the cryolesions were
      correlated with the ultrasound images. Based on the results of these experiments,
      ultrasound-guided cryosurgery of breast cancer was initiated in a human clinical
      trial. RESULTS: In phase 1, a single, short-term (< 7 minutes) freeze killed only
      tumors smaller than 1.5 cm in diameter, despite an apparent decrease to -40
      degrees C at the periphery of each tumor. In phase 2, varying the peripheral
      tumor temperature to as low as -70 degrees C, using a single, short-term (< 7
      minutes) freeze did not alter the results from phase 1. If the ice ball fully
      encompassed the tumor, however, maintaining it for at least 15 minutes achieved
      100% tumor kill independent of tumor size. In phase 3, creation of a reproducible
      ultrasound-monitored cryolesion was facilitated when 2 freeze-thaw cycles were
      performed. No procedure-related complications were noted. In the human trial, 2
      invasive lobular carcinomas from 1 patient were treated by cryosurgery and were
      negative for persistent tumor by core needle biopsy performed 4 and 12 weeks
      after a well-tolerated procedure. CONCLUSIONS: In situ breast cryosurgery has
      been proved to be feasible and efficacious in small and large animal studies and
      has been successfully performed in 1 patient with breast cancer. The results of
      this study suggest that ultrasound-guided cryosurgery of breast cancer warrants
      further investigation.

PMID- 9006550
TI  - An increased incidence of rejection episodes. One of the causes of worse kidney
      transplantation survival in black recipients.
AB  - OBJECTIVE: To evaluate the cause of worse kidney allograft survival in black
      recipients, which has been the source of considerable interest and debate.
      DESIGN: Three hundred ninety-two consecutive renal allografts (O HLA mismatch
      grafts excluded) were reviewed. Of the recipients, 57% were black, 27% received
      living donor grafts, and 86% received their first transplant. All recipients
      underwent an oral cyclosporine induction protocol with triple drug maintenance.
      Crude graft survival, the risk of rejection, and the need for dialysis were
      determined using donor and recipient demographic and immunologic variables.
      RESULTS: Graft survival was 84%, 67%, and 50% at 1, 3, and 5 years after the
      transplantation, respectively. The survival of black recipients was 4%, 11%, and
      20% worse than that of white recipients at 1, 3, and 5 years, respectively (P <
      .002). When only pretransplantation variables were considered, black recipient
      race was the only variable that predicted graft loss in the multivariate analysis
      (relative risk [RR] = 1.6, P = .09). When posttransplantation and
      pretransplantation variables were used, cadaver donor (RR = 1.7), an episode of
      rejection (RR = 2.6), and the need for dialysis (RR = 2.7) were independent
      variables that predicted graft loss (P < .001). Black recipient race was a
      dependent variable. Four pretransplantation variables predicted the risk of
      dialysis: black race (RR = 3.6), male recipient (RR = 2.1), cadaveric donor (RR =
      2.2), and a peak panel-reactive antibody level greater than 30% (RR = 2.8). Three
      pretransplantation variables predicted the risk of rejection: black race (RR =
      1.7), male recipient (RR = 1.6), and a current panel-reactive antibody level
      greater than 30% (RR = 5.3). CONCLUSIONS: These data suggest that black recipient
      race is a dependent predictor of renal allograft survival when the
      posttransplantation events of rejection and dialysis are considered. Black
      recipients have more immunologic complications after renal transplantation that
      result in worse graft survival. These results confirm the importance of
      postallograft events as the major determinants of long-term graft survival and
      suggest that black recipients are receiving inadequate immunosuppression. These
      data support attempts to tailor immunosuppressive protocols to recipient
      pretransplantation risk profiles as a way to improve graft survival in the high
      risk recipient.

PMID- 9006552
TI  - The role of venous outflow obstruction in patients with chronic venous
      dysfunction.
AB  - OBJECTIVE: To quantify the functional venous outflow obstruction with different
      location and extent of obstruction attributed to previous deep vein thrombosis.
      DESIGN: Case-control study. SETTING: Vascular Laboratory, St Mary's Hospital
      Medical School, London, England. PATIENTS: Two groups: group 1, 25 case patients
      and 9 control subjects, and group 2, 45 case patients and 30 control subjects.
      INTERVENTIONS: Ascending venography, duplex scanning, air plethysmography, and
      venous pressure measurements in the foot and the arm via a 21-gauge butterfly
      needle. MAIN OUTCOME MEASURES: Venous outflow fraction (VOF), venous outflow
      resistance (VOR), and arm-foot pressure differential (A-F PD) at rest and after
      reactive hyperemia. RESULTS: Venous outflow resistance was evaluated in group 1.
      Twenty-two case patients underwent VOF testing, and 16 had A-F PD measurement
      performed. Case patients in group 2 underwent VOF testing. Signs and symptoms of
      chronic venous dysfunction were associated with the anatomical extent of
      obstruction. Limb swelling and ache were present in most of the patients; skin
      changes were noted in about 30% and ulceration in 10% of patients. The results of
      all tests showed no evidence of obstruction in control subjects. In most case
      patients with popliteal vein obstruction, test results were similar to those in
      control subjects: the more proximal the veins involved, the more severe the
      obstruction. In 16 case patients, all 3 tests were performed and agreement
      between A-F PD and VOR test results was found in 14 of them. The VOF test results
      agreed with the results of A-F PD and VOR tests in 9 case patients. In group 2,
      50% of the limbs with obstruction proximal to the popliteal vein had a reduced
      VOF, which became worst in the limbs with extensive obstruction, particularly
      when the iliac veins were involved. Of the 73 limbs tested for VOF in both
      groups, only 7 limbs (9.6%) had their venous outflow markedly reduced by
      occlusion of the superficial veins. CONCLUSIONS: The anatomical extent of venous
      obstruction and the development of collateral circulation determine the
      hemodynamic severity of the chronic venous obstruction. The deep collaterals seem
      to be more important than the superficial venous system in bypassing the
      obstruction. The VOR and the A-F PD tests can be used to identify those patients
      who have venous obstruction, whereas the use of the VOF test may reduce the need
      for performing the above tests in 50% of the patients.

PMID- 9006551
TI  - The learning curve for laparoscopic colorectal surgery. Preliminary results from
      a prospective analysis of 1194 laparoscopic-assisted colectomies.
AB  - BACKGROUND: Laparoscopic-assisted colectomy is an emerging technology for
      patients with cancer, polyps, inflammation, and other types of pathologic
      conditions. While previous studies have shown better outcomes for laparoscopic
      cholecystectomies when surgeons perform more procedures, there is no information
      on the relationship between surgeon volume and outcomes for laparoscopic-assisted
      colectomy. OBJECTIVE: To evaluate whether better clinical outcomes are found for
      surgeons who perform higher numbers of laparoscopic-assisted colectomies and
      whether such a relationship, if it exists, applies to both intraoperative and
      postoperative outcomes. DESIGN: Analysis of a data set of 1194 patients, operated
      on by 114 surgeons, from a prospective registry sponsored by the American Society
      of Colon and Rectal Surgeons, from May 1991 to October 1994. MAIN OUTCOME
      MEASURES: Completion rate, intraoperative and postoperative complications, and
      length of hospital stay. RESULTS: In 75% of cases, surgery was completed
      laparoscopically, with no difference between high-volume surgeons (> or = 40
      cases) and low-volume surgeons. Length of stay (average, 6 days) did not vary
      according to surgeon volume. Postoperative complications occurred in 15% of
      cases, with a significantly lower rate for high-volume surgeons (10% vs 19%; P <
      .001). Intraoperative complications occurred in 5% of cases, with a
      nonsignificant trend toward a lower rate for high-volume surgeons (3.7% vs 6.3%).
      A multivariate regression analysis, adjusting for type of disease (cancer vs
      inflammation vs polyps) and for level of difficulty of the procedure (high vs
      low) showed that for high-volume surgeons there is a lower probability of both
      intraoperative complications (adjusted odds ratio, 0.56; 95% confidence interval,
      0.32-0.97; P = .04) and postoperative complications (adjusted odds ratio, 0.48;
      95% confidence interval, 0.34-0.68; P < .001). CONCLUSIONS: There is a learning
      curve for laparoscopic-assisted colectomy with respect to intraoperative and
      postoperative outcomes. As with other laparoscopic procedures, surgeons who
      perform higher volumes of laparoscopic-assisted colectomy have lower rates of
      intraoperative and postoperative complications.

PMID- 9006554
TI  - Shotgun wounds in children. Not just accidents.
AB  - OBJECTIVE: To characterize the demographic characteristics of shotgun wounds in
      children and adolescents across various regions within a state. DESIGN:
      Retrospective case study. SETTING: Accredited trauma centers in Pennsylvania.
      PATIENTS: All patients less than 18 years old who sustained shotgun wounds. DATA
      COLLECTION: Patient data were collected from the Pennsylvania Trauma Systems
      Foundation statewide trauma registry for January 1987 through December 1994. Data
      reviewed included age, race, sex, region, nature of injury, assailant, location
      of incident, length of stay in the hospital and intensive care unit, Injury
      Severity Score, organs injured, death, and discharge disposition. RESULTS: Over 8
      years there were 95 shotgun wounds in patients with a mean +/- SD age of 14.0 +/-
      3.7 years; the male-to-female ratio was 5.8:1. The incidence of shotgun wounds in
      urban areas increased threefold during the second half of the study; the
      incidence in nonurban regions was unchanged. Eighteen deaths (19%) occurred, 17
      (94%) within 24 hours and 10 (56%) because of intracranial injury. Overall,
      unintentional shotgun wounds were most common (n = 46 [48%]), followed by
      assaults (n = 37 [39%]) and suicides (n = 8 [8%]). The highest per capita
      incidence of shotgun wounds occurred in urban areas, typically the result of an
      assault (n = 30 [73%]). In nonurban areas, shotgun wounds were usually
      unintentional (n = 36 [67%]); 34 (63%) occurred in the home. In contrast, in
      urban areas, 26 shotgun wounds (63%) occurred on the street. Overall, 14 fatal
      shotgun wounds (78%) occurred in the home. Operative intervention was required
      for 57 patients (60%). Ultimately, 67 patients (71%) were discharged to home.
      CONCLUSIONS: In urban areas, shotgun wounds are increasing in incidence, often
      occur on the street, and often result from assault. In nonurban areas, shotgun
      wounds are usually unintentional, often occur in the home, and are more often
      lethal than shotgun wounds in urban areas. Multiple-organ injury, surgery, and
      lengthy hospital stays are common.

PMID- 9006553
TI  - Solitary pancreas allografts. The role of percutaneous biopsy and standardized
      histologic grading of rejection.
AB  - OBJECTIVE: To determine the potential impact of ultrasound-guided percutaneous
      pancreas allograft biopsy and standardized histologic grading on graft and
      patient survival in a solitary pancreas transplant program. DESIGN: Retrospective
      case series survey. SETTING: Tertiary care, university teaching hospital.
      PATIENTS: Thirty-five recipients of solitary pancreas transplants. INTERVENTIONS:
      Percutaneous pancreas allograft biopsies were performed in solitary pancreas
      transplant recipients. MAIN OUTCOME MEASURES: Actuarial graft and patient
      survival, cause of graft loss. RESULTS: Initiation of ultrasound-guided
      percutaneous pancreas allograft biopsy with standardized histologic grading is
      associated with a 70% 1-year graft survival and 93% 1-year patient survival in
      solitary pancreas transplantation. Acute rejection was responsible for only 11%
      of cases of graft loss. The presence of endotheliitis, vasculitis, or confluent
      acinar necrosis is associated with decreased pancreas allograft survival, poor
      response to corticosteroid therapy, and shortened time interval to ultimate graft
      loss. Clinical criteria for acute rejection such as elevated serum amylase or
      lipase levels, 50% decrease in urinary amylase levels, unexplained fever, or
      hyperglycemia are associated with a positive predictive value of only 72%.
      CONCLUSION: Pancreas allograft biopsy and standardized histologic grading are
      associated with significantly improved 1-year graft and patient survival in
      solitary pancreas transplantation.

PMID- 9006556
TI  - Enterococcal bacteremia in the surgical intensive care unit. Does vancomycin
      resistance affect mortality? The Johns Hopkins SICU Study Group.
AB  - OBJECTIVE: To determine the incidence and mortality rate associated with
      nosocomial bacteremia caused by vancomycin-resistant Enterococcus in a surgical
      intensive care unit. DESIGN: A retrospective study. SETTING: The surgical
      intensive care unit of a large university hospital tertiary referral center.
      PATIENTS: All patients in the surgical intensive care unit with a documented
      nosocomial bacteremia between January 1, 1992, and December 31, 1994.
      INTERVENTIONS: None. MAIN OUTCOME MEASURE: Mortality rate. RESULTS: Of the 134
      nosocomial bacteremic episodes, 30.6% involved enterococci; 24.4% of the
      enterococci were resistant to vancomycin. Patients with vancomycin-resistant
      enterococcal bacteremia had a significantly longer hospital stay (mean +/- SD, 28
      +/- 18 vs 12 +/- 10 days; P = .005) and were more likely to have been treated
      with vancomycin (70% vs 10.3%; P = .001) than patients with vancomycin-sensitive
      enterococcal bacteremia. The mortality (41.0%) associated with enterococcal
      bacteremia was similar to the overall bacteremic mortality (41.7%). There was no
      difference in episode-specific mortality associated with vancomycin-resistant
      enterococci (40%) vs vancomycin-sensitive enterococci (38.7%). Of the 4 deaths
      associated with vancomycin-resistant enterococcal bacteremia, only 2 occurred
      within 14 days of the bacteremia, as did 8 of 12 deaths associated with
      vancomycin-sensitive enterococcal bacteremia (P = .64). CONCLUSIONS: Enterococci
      were the most commonly isolated nosocomial blood-borne pathogens in the surgical
      intensive care unit. Nearly 25% of the enterococcal bacteremic episodes were
      resistant to vancomycin. Vancomycin-resistant Enterococcus is associated with a
      prolonged hospital stay and with vancomycin use. Nevertheless, vancomycin
      resistance itself does not increase the mortality rate associated with
      enterococcal bacteremia.

PMID- 9006555
TI  - Delayed administration of inhaled nitric oxide preserves alveolar-capillary
      membrane integrity in porcine gram-negative sepsis.
AB  - OBJECTIVE: To determine the effect of delayed administration of inhaled nitric
      oxide (NO) on acute lung injury after the onset of gram-negative sepsis. DESIGN:
      Nonrandomized controlled study. SETTING: University medical center laboratory.
      SUBJECTS: Yorkshire swine. INTERVENTIONS: Five groups of swine were anesthetized,
      mechanically ventilated, and studied for 5 hours. After surgical preparation,
      control (n = 10) and NO-treated control (n = 6) animals received a 1-hour
      infusion of sterile saline solution. Sepsis was induced with a 1-hour intravenous
      infusion of live Pseudomonas aeruginosa. Untreated animals with sepsis (n = 10)
      received no treatment. Inhaled NO at 20 ppm was administered to NO30-treated
      animals with sepsis (n = 7) and NO60-treated animals with sepsis (n = 8)
      beginning at 30 and 60 minutes after bacterial infusion was begun, respectively.
      MAIN OUTCOME MEASURES: Systemic and pulmonary hemodynamics, arterial blood gas
      determination, bronchoalveolar lavage protein and neutrophil content, neutrophil
      oxidant burst, lung myeloperoxidase content, and scanning electron micrographic
      studies. RESULTS: A progressive, significant (P < .05) decline in PaO2 developed
      in untreated animals with sepsis, which was prevented in NO30- and NO60-treated
      animals with sepsis. A significant (P < .05) increase in bronchoalveolar lavage
      protein and neutrophil counts compared with baseline values was observed in
      untreated animals with sepsis, indicating acute lung injury. These variables
      exhibited no notable increase in NO30- and NO60-treated animals with sepsis and
      were significantly (P < .05) reduced compared with untreated animals with sepsis.
      The lung myeloperoxidase content was significantly (P < .05) elevated at 5 hours
      in all groups with sepsis compared with baseline values and the control and NO
      treated control groups. The total phorbol myristate acetate-induced
      polymorphonuclear leukocyte oxidant burst at 5 hours was significantly (P < .05)
      decreased in the NO30- and NO60-treated animals with sepsis compared with
      untreated animals with sepsis. Untreated and NO30- and NO60-treated animals with
      sepsis showed a significant (P < .05) increase in pulmonary artery pressure at 30
      minutes, followed by a progressive decline. These changes were significant (P <
      .05) compared with baseline values and the control groups. No significant (P <
      .05) difference in pulmonary artery pressure or systemic arterial pressure was
      found at any time between untreated and NO30- and NO60-treated animals with
      sepsis. CONCLUSIONS: The delayed administration of inhaled NO preserves alveolar
      capillary membrane integrity in this porcine model of gram-negative sepsis. The
      inhibition of neutrophil transendothelial migration, rather than neutrophil
      rolling or tight adhesion, may be a critical mechanism by which inhaled NO
      produces this effect. Decreased oxidant production by activated neutrophils may
      be a secondary mechanism by which inhaled NO reduces acute lung injury.

PMID- 9006557
TI  - Treatment of endotoxemic mice with anti-interleukin-6 antibody paradoxically
      increases interleukin-6 levels and stimulates mucosal protein synthesis.
AB  - OBJECTIVE: To test the role of interleukin-6 (IL-6) in the regulation of mucosal
      protein synthesis during endotoxemia. EXPERIMENTAL DESIGN: Three series of
      experiments were performed: (1) mice were injected with different doses of
      lipopolysaccharide (LPS) and protein synthesis was measured in jejunal mucosa at
      various time points up to 24 hours after injection of LPS; (2) mice were
      pretreated with anti-IL-6 antibody before injection of LPS; and (3) mice were
      injected with recombinant IL-6 and mucosal protein synthesis was measured 24
      hours later. RESULTS: Treatment of mice with LPS resulted in a dose- and time
      dependent increase in mucosal protein synthesis. Pretreatment of endotoxemic mice
      with anti-IL-6 antibody resulted in a paradoxical increase in plasma and tissue
      levels of IL-6 and a further increase in mucosal protein synthesis.
      Administration of IL-6 to normal mice resulted in increased mucosal protein
      synthesis. CONCLUSION: The increase in mucosal protein synthesis seen during
      endotoxemia may be regulated at least in part by IL-6.

PMID- 9006558
TI  - Effect of bombesin on impairment of upper respiratory tract immunity induced by
      total parenteral nutrition.
AB  - OBJECTIVE: To determine the effect of the neuropeptide bombesin on total
      parenteral nutrition-induced impairment of upper respiratory tract immunity.
      DESIGN: Randomized, controlled trial. PARTICIPANTS: Thirty-six adult male
      Institute for Cancer Research mice weighing 25 to 35 g. INTERVENTIONS: Mice were
      inoculated intranasally with H1N1 virus. At 3 weeks, mice were randomized to
      receive chow plus intravenous saline (n = 12), intravenous total parenteral
      nutrition (n = 12), or intravenous total parenteral nutrition plus bombesin (n =
      12) administered 3 times daily at 15 micrograms/kg. After 5 days, mice were
      rechallenged with intranasal virus and killed at 40 hours to determine viral
      shedding from the respiratory tract; normal convalescent mice do not shed virus
      because of intact IgA-mediated mechanisms. MAIN OUTCOME MEASURES: Viral shedding
      was determined by collection of nasal secretions. Samples were diluted and
      incubated with a suspension of Madin-Darby canine kidney cells. Viral growth was
      determined by hemagglutination. RESULTS: Body weight was similar between the
      total parenteral nutrition and bombesin groups; however, both were significantly
      lower than that in the chow group (P < .05). After 6 days of feeding, no mice in
      the chow group shed virus, compared with 6 (50%) of the mice in the total
      parenteral nutrition group. Of the mice in the bombesin group, only 1 was
      positive for viral shedding. The total parenteral nutrition group showed
      increased viral shedding compared with both the chow group (P < .01) and the
      bombesin group (P < .05). CONCLUSIONS: Exogenous administration of bombesin
      reversed the total parenteral nutrition-associated impairment of upper
      respiratory tract immunity to an IgA-mediated infectious challenge. These
      observations support the concept of a common mucosal immune system, since
      neuropeptides are endogenous to the gastrointestinal and respiratory tracts.
      Hormonal modulation of immunity is a promising avenue of treatment for patients
      who require total parenteral nutrition.

PMID- 9006559
TI  - Academic surgeons' knowledge of Food and Drug Administration regulations for
      clinical trials.
AB  - OBJECTIVES: To identify knowledge levels of academic surgeons about Food and Drug
      Administration (FDA) and Institutional Review Board (IRB) regulations for
      clinical research and to determine whether being a member in an IRB, conducting
      or participating in clinical trials, or being a member in surgical societies
      affected knowledge levels. DESIGN: Survey of surgical department faculty members
      in 20 universities. RESULTS: Sixty-five responses were received from 14 sites.
      Overall mean (+/- SEM) correct score was 6.7 +/- 0.2 of a possible 20 points. The
      best predictor of overall score was being a primary investigator of a clinical
      trial (P < .001), followed by being or having been a member of an IRB (P < or =
      .02). The total mean score of members of the Surgical Infection Society (8.2 +/-
      0.5) was significantly higher (P < .001) than that of nonmembers (6.1 +/- 0.2), a
      phenomenon not observed with other surgical societies. In certain hypothetical
      clinical scenarios, all respondents were mistakenly willing to conduct clinical
      trials without obtaining appropriate approval from the FDA. Four (22%) of 18 IRB
      member respondents and 16 (25%) of the 65 respondents were willing to conduct
      human research without appropriate approval from patients, the IRB, or both.
      CONCLUSIONS: Knowledge deficits exist in the academic surgical community about
      the role and requirements of the FDA and local IRBs for conducting clinical
      research. Further study is required to determine the reasons for this deficit and
      to identify appropriate interventions.

PMID- 9006560
TI  - Racial factors cannot explain superior Japanese outcomes in stomach cancer.

PMID- 9006561
TI  - Patterns of initial management of node-negative breast cancer in two Canadian
      provinces. British Columbia/Ontario Working Group.
AB  - OBJECTIVE: To describe the patterns of initial management of node-negative breast
      cancer in Ontario and British Columbia and to compare the characteristics of the
      patients and tumours and of the physicians and hospitals involved in management.
      DESIGN: Retrospective, population-based, cohort study. PARTICIPANTS: All 942
      newly diagnosed cases of node-negative breast cancer in 1991 in British Columbia
      and a random sample of 938 newly diagnosed cases in Ontario in the same year.
      OUTCOME MEASURES: Number and proportion of patients with newly diagnosed node
      negative breast cancer who received breast-conserving surgery (BCS) or mastectomy
      and who received radiation therapy after BCS. RESULTS: BCS was used in 413 cases
      (43.8%) in British Columbia and in 634 cases (67.6%) in Ontario (p < 0.001).
      After BCS, radiation therapy was received by 378 patients (91.5% of those who had
      undergone BCS) in British Columbia and 479 patients (75.6% of those who had
      undergone BCS) in Ontario (p < 0.001). In both provinces, lower patient age,
      smaller tumour size, a noncentral unifocal tumour, absence of extensive ductal
      carcinoma in situ and initial surgery by a surgeon with an academic affiliation
      were associated with greater use of BCS. Lower patient age and larger tumour size
      were associated with greater use of radiation therapy after BCS in both
      provinces. CONCLUSION: Patient, tumour and physician factors are associated with
      the choice of initial management of breast cancer in these two Canadian
      provinces. However, the differences in management between the two provinces are
      only partly explained by these factors. Other possible explanations, such as the
      presence of provincial guidelines, differences in the organization of the health
      care system or differences in patient preference, require further research.

PMID- 9006562
TI  - Declining sex ratios in Canada.
AB  - OBJECTIVE: To examine the trends in the proportion of annual live births that
      were male in Canada and to compare the trends with those in the United States.
      DESIGN: Analysis of census data. SETTING: Canada as a whole and 4 main regions
      (West, Ontario, Quebec and Atlantic). SUBJECTS: All live births from 1930 to
      1990. OUTCOME MEASURES: Sex ratio (expressed as the proportion of total live
      births that were male [male proportion]) overall and by region. RESULTS: The male
      proportion in Canada decreased significantly after 1970 (p < 0.001); this
      represented a cumulative loss of 2.2 male births per 1000 live births from 1970
      to 1990. Although a decrease was observed in all four regions studied, only that
      in the Atlantic region was significant (p < 0.001), representing a cumulative
      loss of 5.6 male births per 1000 live births from 1970 to 1990. A significant
      decrease in the male proportion was also observed in the United States from 1970
      to 1990 (p < 0.001), although to a lesser degree than that observed in Canada,
      and represented a cumulative loss of 1.0 male births per 1000 live births.
      CONCLUSIONS: The decreased sex ratio in Canada adds to the growing debate over
      changes in biological markers and their potential causes. In addition, the study
      illustrates the potential use of the sex ratio as a widely available, unambiguous
      measure of the reproductive health of large populations.

PMID- 9006563
TI  - A surgical subculture. The use of mastectomy to treat breast cancer.
AB  - The results of the study by Dr. Vivek Goel and associates (see page 25 of this
      issue) are similar to those of studies conducted in the United States that have
      found that the use of breast-conserving surgery to treat breast cancer is
      inconsistent. The current understanding of the biological basis of the treatment
      of breast cancer stresses the limited role of extensive surgery and the value of
      radiation therapy and other forms of adjuvant treatment in reducing the rates of
      local recurrence. During the Montreal Forum on Breast Cancer, held in November
      1992, participants expressed a wish for consistency in medical practice in this
      area. However, the goal of consistency may not be served by guidelines that
      present only a summary of scientific findings. Guidelines must present clear
      recommendations, and the diffusion of these recommendations into general medical
      practice must involve regional medical groups and their opinion leaders.

PMID- 9006564
TI  - Is Canada's sex ratio in decline?
AB  - In this issue (see pages 37 to 41) Dr. Bruce B. Allan and associates report a
      small but statistically significant decrease--of about 0.2%--in the proportion of
      male live births in Canada over the period 1970-90. In this editorial, factors
      that have been reported in the literature to influence sex ratio are examined
      within a Canadian context. The authors suggest that although the reasons for the
      apparent decline in the sex ratio in Canada are unclear, the increasing use of
      ovulation induction may be a contributing factor. Data from the Nova Scotia Atlee
      Perinatal Database are discussed with a view to explaining the trend observed in
      Atlantic Canada, but no obvious explanation emerges. The authors argue that when
      the period of observation is extended no overall change in the sex ratio is
      apparent. This would suggest a tendency toward stabilization rather than decline.

PMID- 9006565
TI  - Findings of negligence followed communication lapses in BC aneurysm case.
AB  - Negligence is sometimes established on the basis of lapses in communication and
      patient care management that, in hindsight, could have been avoided. A recent BC
      court case concerned a patient who died because of a ruptured aneurysm. A Supreme
      Court judge found that some of the physicians involved had failed in their duty
      to diagnose the patient's condition properly, or failed to communicate to one
      another significant signs of the patient's illness, and failed to refer him in
      time to the medical specialists who could have diagnosed and treated his
      condition promptly.

PMID- 9006566
TI  - Too close for comfort? A family physician questions whether medical professionals
      should be excluded from their loved ones' care.

PMID- 9006567
TI  - Malaria in Canada.

PMID- 9006568
TI  - Disability payments continue to climb. "Tell us what you see, not what you
      think," CPP tells MDs.
AB  - Growing concern about the sustainability of the Canada Pension Plan has led to a
      closer look at the disability benefits it provides. The federal auditor general
      reported recently that the number of recipients has almost doubled in the past 10
      years, and disability payments have more than tripled, to $3 billion annually.
      This article looks at the role physicians play in determining whether an
      applicant is disabled.

PMID- 9006569
TI  - Too much money wasted on frivolous applications for CPP disability benefits.
AB  - Family physician Samuel Shortt discusses Canada Pension Plan disability-benefit
      applications from the doctor's perspective. He thinks physicians are being forced
      to complete too many of the forms that have little if any chance of being
      approved.

PMID- 9006570
TI  - Micmac medical student becomes role model for his community.
AB  - When Robert Johnson graduates from medical school in 1998, he will become
      Canada's first Micmac physician. For him, going to medical school is a major
      responsibility because he is a role model for an entire community. He hopes he is
      only the first of many Micmacs to make this career choice.

PMID- 9006571
TI  - Canada's largest magnet finds home in new MRI program in London.
AB  - Canada's largest magnet, which is now making functional magnetic resonance
      imaging possible at Ontario's Robarts Research Centre, is expected to cast some
      light on mysteries buried within the brain. With the huge magnet, said Dr. Ravi
      Menon, "I can distinguish between centres that control the thumb and the index
      finger."

PMID- 9006573
TI  - Independent medical examinations and the fuzzy politics of disclosure.
AB  - The number of third-party independent medical examinations is increasing, and so
      is the controversy surrounding them. Dorothy Grant of the Medical Society of Nova
      Scotia provides advice on how physicians should address this potentially
      contentious issue.

PMID- 9006574
TI  - Primary pulmonary hypertension and long-term use of appetite suppressants.

PMID- 9006576
TI  - Congenital anomalies and fluconazole.

PMID- 9006575
TI  - HIV protease inhibitors and increased bleeding in hemophilia?

PMID- 9006577
TI  - CMAJ launches new online-medicine page.

PMID- 9006578
TI  - Molecular genetics in clinical practice: the series begins.

PMID- 9006579
TI  - Wide complex tachycardia.

PMID- 9006580
TI  - Unusual pathogen in a man with HIV infection.
AB  - A 41-year-old man who had tested positive for HIV infection presented with cough,
      yellow sputum, fever, and chills of 10 days' duration. He was short of breath at
      rest and had a poor appetite. He did not have chest pain, bloody sputum, or
      weight loss.

PMID- 9006581
TI  - Case in point. Digital infarction secondary to radial artery cannulation.

PMID- 9006582
TI  - Sequencing the human genome.
AB  - By 2005, or sooner, the three billion code letters of a representative human
      genome will be known, along with the locations of all of its genes. Even today,
      however, the work is greatly accelerating identification of disease-related
      genes. One outcome will be tests for genetic components of risk in the majority
      of common illnesses. In the longer run, genetic discoveries will surely lead to
      new treatments.

PMID- 9006583
TI  - Screening for colorectal cancer.
AB  - Second only to lung cancer in mortality, colon cancer is amenable to cure if
      detected early. Because fecal occult blood testing and flexible sigmoidoscopy are
      effective individually but have limitations, both are now recommended for
      screening. However, after successful polyp removal, surveillance colonoscopy does
      not need to be performed as often as previously thought.

PMID- 9006584
TI  - Growth hormone in adults: indications and implications.
AB  - Adults with hypopituitarism and documented growth hormone deficiency are now
      eligible for replacement therapy. What are the guidelines for diagnosis and
      treatment? More broadly, what are the implications for other adults with
      hyposomatotropism-namely, the elderly? And is there a therapeutic role for the
      hormone in patients with disease states such as osteoporosis, heart failure, and
      acute catabolic illness?

PMID- 9006586
TI  - Spontaneous echo contrast and thromboembolism.
AB  - Spontaneous echocardiographic contrast (a swirling, smokelike haze that appears
      in blood during imaging) indicates a predisposition to thromboembolism,
      particularly in patients with atrial fibrillation and elevation of hematocrit,
      ESR, and serum fibrinogen.

PMID- 9006585
TI  - Low-molecular-weight heparin for venous thromboembolism.
AB  - For prophylaxis and treatment of venous thromboembolism, low-molecular-weight
      heparin is as effective as standard, unfractionated heparin and has fewer adverse
      effects. Moreover, selected patients can use it at home.

PMID- 9006587
TI  - Improving office delivery of preventive care.

PMID- 9006588
TI  - Topical analgesics: are they underused?

PMID- 9006589
TI  - Abdominal discomfort in a man with sprue.

PMID- 9006590
TI  - Dysuria in an elderly man with cardiomyopathy.

PMID- 9006591
TI  - Bilateral movement disorder in a patient with AIDS.

PMID- 9006593
TI  - Lurking under the bridge to 2001: telemalpractice.

PMID- 9006594
TI  - Costs: measuring the economic burden of Alzheimer's disease care.

PMID- 9006592
TI  - A nurse with neck pain and fever after a needle-stick.

PMID- 9006595
TI  - Making tough choices in a changing healthcare arena.

PMID- 9006596
TI  - Understanding personal risk taking among staff nurses: critical information for
      nurse executives.

PMID- 9006597
TI  - Quantum mechanics and the future of healthcare leadership.
AB  - It is a new age for healthcare. No longer can the past roles and behaviors of
      leadership be applied to the emerging models of health service delivery, the
      elements of the quantum age will change forever the leadership characteristics
      and roles necessary to thrive in the emerging age.

PMID- 9006598
TI  - Improving care givers' satisfaction with information received during
      hospitalization.
AB  - As competition for patient volume escalates among hospital providers,
      administrators must identify ways to attract new patients and maintain or
      increase patient volume. Family care givers are known to greatly influence
      individuals' choices in these matters of selection of healthcare services and
      providers. The results of a successful nurse-initiated daily phone calls program,
      designed to improve family care giver satisfaction by enhancing the provision of
      patient-specific information, are presented. The components of the program,
      associated costs, and implications on delivery of care are discussed.

PMID- 9006600
TI  - An interactive quality of work life model applied to organizational transition.
AB  - Most healthcare organizations in the United States are in the process of some
      type of organizational change or transition. Professional nurses and other
      healthcare providers practicing in U.S. healthcare delivery organizations are
      very aware of the dramatic effects of restructuring processes. A phenomenal
      amount of change and concern is occurring with organizational redesign,
      generating many questions and uncertainties. These transitions challenge the
      basic assumptions and principles guiding the practice of clinical and management
      roles in healthcare.

PMID- 9006601
TI  - A flexible staffing model for patient service associates.
AB  - A flexible staffing model for the patient service associate (PSA), a type of
      multiskilled worker, was developed at an academic medical center. The model uses
      the patient census, admissions, and discharges on a patient care unit to
      determine how many PSAs are needed during a 24-hour period. The authors discuss
      the staffing model's effects on labor costs and the quality of PSA work.

PMID- 9006599
TI  - Registered nurse role changes and satisfaction with unlicensed assistive
      personnel.
AB  - This study examines registered nurse perceptions of changes in the role of the
      registered nurse and registered nurse satisfaction with the use of unlicensed
      assistive personnel in acute hospital care delivery systems. Six major functional
      areas were examined: leadership, communication patterns, health teaching,
      evaluation activities, care management responsibilities, and unit tasks. Moderate
      to profound changes were reported in areas relating to the team leader role.
      Registered nurses reported dissatisfaction with unlicensed assistive personnel's
      ability to perform delegated nursing tasks, communicate pertinent information,
      and provide more time for professional nursing activities.

PMID- 9006603
TI  - The 21st-century hospital.

PMID- 9006602
TI  - Guns and suicide in Australia.

PMID- 9006604
TI  - Women and men and the medical work force in Australia.

PMID- 9006605
TI  - The GP-hospital interface: attitudes of general practitioners to tertiary
      teaching hospitals.
AB  - OBJECTIVE: To assess general practitioner (GP) perceptions of liaison with two
      local tertiary teaching hospitals. DESIGN: Questionnaire-based survey of GP
      attitudes. SETTING: Melbourne and North West Melbourne Divisions of General
      Practice, in July and September 1994. PARTICIPANTS: All GPs (587) practising in
      the Divisions (identified from Health Insurance Commission lists of consultations
      charged at GP rates). OUTCOME MEASURES: Degree of agreement on a 5-point Likert
      scale to statements about GP-hospital liaison, and relevant open comments.
      RESULTS: 350 GPs (60%) responded, including 84% of vocationally registered GPs;
      68% of the 350 were in full-time practice and 70% had been in practice for over
      10 years. GPs had no clear strategy for obtaining admission of semi-urgent
      patients to public hospitals. For patients needing urgent admission, almost a
      third of GPs sometimes resorted to sending them to the emergency department
      without first telephoning. Most GPs agreed that hospitals did not notify them of
      patient admission (84%), major changes in patient condition, including death
      (87%), and patient discharge (75%). Most would interrupt a consultation to
      discuss a patient with hospital staff (92%). About half agreed they had poor
      access to outstanding results, and 65% were concerned that proposed early
      discharge practices would be detrimental to patient care. CONCLUSIONS: The survey
      identified considerable GP dissatisfaction with hospital-GP communication and GP
      willingness to be more involved in liaison and communication with hospitals about
      patient care. Changes in hospital organisation and hospital staff attitudes are
      needed to allow this.

PMID- 9006607
TI  - What is the future of the hospital system?

PMID- 9006606
TI  - Crying in hospitals: a survey of doctors', nurses' and medical students'
      experience and attitudes.
AB  - OBJECTIVE: To investigate doctors', nurses' and medical students' experiences
      with, and attitudes of health care personnel towards, crying in hospitals.
      DESIGN: Descriptive, cross-sectional study, using self-report questionnaires.
      SETTING AND PARTICIPANTS: The sample comprised 52 doctors (response rate, 33%)
      and 103 nurses (response rate, 58%) from three Sydney metropolitan general
      hospitals, and 101 sixth-year medical students (response rate, 99%). RESULTS:
      Crying was frequent in hospitals; 57% of doctors, 76% of nurses and 31% of
      medical students had cried at work in the hospital at least once, and women cried
      significantly more often than men. Being a nurse significantly increased, whereas
      being a medical student significantly decreased, the likelihood of crying.
      Medical students reported the highest percentage of negative social consequences
      of their own crying (e.g., being ridiculed or screamed at). The main reason for
      all respondents' crying was identification and bonding with suffering and dying
      patients or their families. The respondents generally viewed crying by patients
      as a healthy response, and they were empathetic towards the crying patient. About
      one-third of the respondents were interested in (or would consider) using
      psychological help to explore their own emotional reactions to crying.
      CONCLUSION: Despite its limited sample, this study suggests that the topic of
      "crying" should be included in medical training, and that support be provided for
      medical staff who are distressed by crying behaviour in hospitals.

PMID- 9006609
TI  - Breast cancer in rural Australia.

PMID- 9006608
TI  - Lead poisoning in an electrician: a bad substitute for a bad habit.
AB  - An electrician presented with a four-month history of unexplained abdominal pain
      and constipation, which had prompted four hospital admissions and numerous
      investigations. Blood-film results suggested lead poisoning, and an occupational
      history revealed that he had chewed about a metre of electrical cable (which
      contains lead) daily for 10 years as a substitute for smoking.

PMID- 9006611
TI  - The changing face of pathology in Australia: implications for public and private
      services.
AB  - Dramatic changes in pathology services in Australia over the past few decades
      have radically altered the way the discipline is practised. Although these
      developments are not unique to Australia, the recent pace of change in this
      country has been particularly rapid. It is time to reflect on the course of
      events, examine the issues and (possibly) predict the future.

PMID- 9006610
TI  - Breast cancer management: a rural perspective.
AB  - Audit of a general surgical practice in the rural Victorian town of Echuca
      identified 28 new patients with breast cancer between September 1992 and August
      1995 (10% of those with breast conditions). The rural setting was no impediment
      to breast conservation (achieved in 68% of the 25 who had surgery) or to a
      multidisciplinary approach (management was planned in conjunction with an
      oncologist and/or specialist breast surgeon for 26 of the 28 patients).

PMID- 9006612
TI  - Gout and other crystal arthropathies.

PMID- 9006613
TI  - Palliative care: an update on "terminal restlessness".
AB  - Terminal restlessness is a variant of delirium observed in some patients in their
      last days of life. Readily reversible causes of restlessness should be identified
      and treated. Benzodiazepines give effective palliation of this condition, and,
      unlike haloperidol and the phenothiazines, do not exacerbate the existing
      tendency to myoclonus and convulsions.

PMID- 9006614
TI  - Safe practices in cyberspace: a medical perspective on computer viruses.

PMID- 9006615
TI  - The portrayal of the doctor in non-medical literature: the impaired doctor.

PMID- 9006616
TI  - Blood lead concentrations and iron status of preschool children from low income
      families.

PMID- 9006617
TI  - Lead toxicity in a car radiator worker.

PMID- 9006618
TI  - Methadone-related deaths in New South Wales.

PMID- 9006619
TI  - How will society handle people with presymptomatic genetic disease?

PMID- 9006620
TI  - The significance of birthmarks.

PMID- 9006621
TI  - Delayed dermatitis from contact with hydrofluoric acid.

PMID- 9006622
TI  - Sudden infant death syndrome in New Zealand: where to next?

PMID- 9006623
TI  - The characteristics and outcomes for patients presenting with unintentional
      domestic injuries to general practice.
AB  - AIM: To describe domestic unintentional injuries in three large, computerised
      general practices in the Wellington area. METHOD: Details of all domestic
      injuries were recorded from Accident Compensation Corporation (ACC) forms.
      RESULTS: Initial consultations for domestic unintentional injuries counted for
      29.4% of all injuries for which ACC forms were completed and represented 1.2% of
      all patient contacts. The very young and elderly presented more frequently with
      domestic unintentional injuries. The types of injury and the injury incident
      varied between age groups. Most (75%) of the injured patients were treated by the
      practices without referral. CONCLUSION: Most (96%) of the patients who presented
      with domestic unintentional injuries were registered patients of the practices.
      This relationship provides an important opportunity for general practitioners to
      advise patients about accident prevention. More research is needed to compare the
      presentation of domestic unintentional injuries in general practice and in
      hospitals with accidents in the community.

PMID- 9006624
TI  - Acute renal failure in the paediatric intensive care unit.
AB  - AIMS: To review a group of children with acute renal failure (ARF) requiring
      renal replacement therapy in a paediatric intensive care unit (PICU). METHODS:
      Case records of children admitted to paediatric intensive care unit between
      January 1992 and July 1995 were reviewed for demography, diagnosis, modality of
      treatment, duration, complications of therapy and renal outcome. Long term follow
      up was sought from patients' referring paediatricians. RESULTS: Twenty children
      with a mean age of 2 years and 3 months required acute renal replacement therapy.
      The most common cause was diarrhoea associated haemolytic uraemic syndrome with a
      mean duration of dialysis of 11.5 (SD 3.1) days (range 5-15. Four children had
      septicaemic illnesses; three with multiorgan system failure, one of whom died.
      Peritoneal dialysis was the only modality in 16 patients and four children were
      treated with continuous venovenous haemofiltration. Eight of the 20 patients were
      discharged from the paediatric intensive care unit with normal renal function as
      judged by serum creatinine. Long-term follow up showed normalisation of serum
      creatinine in a further eight of ten patients. CONCLUSIONS: The most common cause
      of acute renal failure was diarrhoea associated haemolytic uraemic syndrome with
      an excellent outcome (100% patient survival). Children who had acute renal
      failure due to other illnesses had a higher mortality (27%).

PMID- 9006625
TI  - Trends in gastrointestinal decontamination for deliberate self poisoning in
      Christchurch.
AB  - AIM: To examine changes in the choice of gastrointestinal decontamination for
      deliberate self poisoning in Christchurch. METHOD: A review of adult deliberate
      self poisoning cases for 9 months from July 1 1995 to March 31 1996 and a
      comparison with previously published figures from 1989 and 1992. RESULTS: Only 5%
      of patients received gastric lavage (compared with 26% in 1992 and 78% in 1989)
      and 52% received activated charcoal (compared with 46% in 1992 and 0.4% in 1989).
      No patients received syrup of ipecacuanha (compared with 1% in 1992 and 25% in
      1989) and 43% had no gastrointestinal decontamination at all. CONCLUSION: The
      trend towards the use of activated charcoal and away from gastric lavage is
      consistent with sentiments expressed in the literature.

PMID- 9006626
TI  - Hepatitis B infection in households of HBsAg positive New Zealand children.
AB  - AIMS: To determine, from data obtained in a school-based hepatitis B vaccination
      programme, the prevalence of hepatitis B virus (HBV) infection in household
      contacts of children found to be hepatitis B surface antigen (HBsAg) positive.
      METHODS: Children who were HBsAg positive were visited in their homes 6 months or
      more after their initial blood test. Blood was drawn to confirm HBsAg status, and
      to ascertain HBeAg status. Their household contacts were tested for HBV
      seromarkers. RESULTS: Visits were made to homes of 931 children initially found
      to be HBsAg positive. Nine hundred and seven of these children (97.4%) were still
      HBsAg positive and thus confirmed to be chronic HBsAg carriers. The testing of
      2957 household contacts of HBsAg positive schoolchildren revealed that 719
      (24.3%) were HBsAg positive, a rate many times higher than that in the
      schoolchildren initially tested. Total HBV seromarker rates were highest in Asian
      households, and lowest in Europeans where 57% had been infected and 12% were
      HBsAg positive. Ethnic differences were largely accounted for by variation in
      maternal HBsAg status, reflecting different rates of perinatal infection.
      CONCLUSIONS: All family and household contacts of individuals identified as
      presumptive HBsAg carriers should be tested for HBV seromarkers as a routine. It
      is particularly important to ensure full prophylaxis against perinatal infection.

PMID- 9006627
TI  - Cutaneous myiasis due to Dermatobia hominis: case report.

PMID- 9006628
TI  - Views of Pacific Islands people with noninsulin dependent diabetes: a Wellington
      survey.
AB  - AIMS: The aims of the study were: (1) to ascertain the views of Pacific Islands
      people with diabetes on diabetes services they are receiving, and (2) to identify
      their perceptions on their health and diabetes related problems. METHODS: A
      random sample survey of Wellington and Kenepuru diabetes clinics and the
      Wellington Pacific Islands community was undertaken using person to person
      interviews by seven trained Pacific Islands interviewers. The Tokelau Migrant
      Study questionnaire of Dr Ian Prior formed the basis for the questions used in
      this study. RESULTS: The sample size was 120. Response rate 82.2%. Samoans were
      the main ethnic group at 62% and women the dominant gender at 75%. Mean age was
      46%. Eighty eight percent presented with symptoms at diagnosis and 64% had
      diabetes of 5 years standing or more. Seventy eight percent were on diet and/or
      tablets and 73% reported having complications of which visual impairment was the
      most common. Twenty four percent were not happy with the current service. Fifty
      nine percent knew little or nothing about diabetes and 78% expressed a desire to
      know more. Good control was reported by 59%, and 66% reported they followed a
      diet. Forty five percent admitted having an overweight problem and 57% reported
      losing weight since diabetes diagnosed. Forty five percent knew how to test their
      blood sugar and 26% tested at home. Eighty nine percent favoured a specific
      service for Pacific Islands people with education being the major emphasis. More
      than a third preferred service to be near home and run by Pacific Islands health
      professionals. CONCLUSION: The majority of Pacific Islands people developed
      symptoms before going to see a doctor. It indicated that the majority have
      suffered from diabetes for a long time before seeking medical care for the first
      time. Most indicated being happy with the services they are receiving from their
      family doctors but if given a choice they would prefer a service specifically for
      themselves. Diabetes education as well as a treatment clinic were services most
      favoured with the preference close to home and to be delivered by Pacific Islands
      health professionals.

PMID- 9006630
TI  - Photodermatitis from sunscreen.

PMID- 9006629
TI  - Percutaneous biopsy of operable liver lesions: is it necessary or advisable?
AB  - AIM: The necessity and desirability of performing percutaneous biopsy of
      potentially resectable liver tumours is called into question. METHODS: Two cases
      are reported in which percutaneous biopsy of resectable liver tumours was
      performed unnecessarily and resulted in needle track seeding. RESULTS: In both
      instances patients who underwent potentially curative liver resection were
      rendered incurable because of biopsy track recurrence. CONCLUSION: The common
      practice of performing percutaneous ultrasound or CT guided biopsy of potentially
      resectable lesions in the liver is generally neither necessary nor desirable.

PMID- 9006631
TI  - Underutilisation of primary medical care services by Maori and low income New
      Zealanders.

PMID- 9006632
TI  - An increase in SIDS among Pacific Island infants--is it real?

PMID- 9006633
TI  - Request from insurance companies.

PMID- 9006634
TI  - Achilles tendon rupture due to ciprofloxacin.

PMID- 9006635
TI  - Headrest position during normal driving: implication to neck injury risk in rear
      crashes.
AB  - The gap and relative height of headrest behind drivers were determined for 1915
      vehicles approaching an intersection on a two lane road. Vehicle type and
      headrest adjustment were also evaluated using film of normal driving taken by the
      Insurance Institute for Highway Safety. Only 10% of drivers had headrests in the
      most favorable position to prevent neck extension during a rearend crash. 73% of
      cars had adjustable headrests, but only a quarter were placed in the up position.
      83% of the adjustable headrests could have been raised to better protect the
      driver. Hyge sled tests were run to determine biomechanical responses for the
      various conditions observed in normal driving. This included three headrest
      heights and three gaps behind the head. Neck extension from the Hybrid III dummy
      was normalized to the response for a high, close headrest, and injury risk was
      assumed to be proportional to neck extension. The current driving situation has a
      relative injury risk of 3.4 in rearend crashes, compared to 1.0 for the favorable
      condition. If all adjustable headrests were placed in the up position, the
      relative risk would be lowered to 2.4, a 28.3% reduction in whiplash injury risk.
      Public education and vehicle design should address the importance of proper
      headrest placement for driving safety.

PMID- 9006637
TI  - A meta-analysis of studies concerning the safety effects of daytime running
      lights on cars.
AB  - A meta-analysis of 17 studies that have evaluated the effects on traffic safety
      of using daytime running lights (DRL) on cars is presented. A distinction is made
      between studies that have evaluated the effects of DRL on the accident rates of
      each car using it and studies that have evaluated changes in the total number of
      accidents in a country following the introduction of mandatory use of DRL. Three
      different definitions of the measure of safety effects are compared and their
      validity discussed. It is concluded that the use of DRL on cars reduces the
      number of multi-party daytime accidents by about 10-15% for cars using DRL. The
      estimated effects on the total number of accidents of introducing DRL laws are
      somewhat smaller, 3-12% reduction in multi-party daytime accidents, and are
      likely to contain uncontrolled confounding effects. There is no evidence to
      indicate that DRL affects types of accident other than multi-party daytime
      accidents.

PMID- 9006636
TI  - Predictive validity and internal consistency of the pre-hospital index measured
      on-site by physicians.
AB  - Physiological measures of injury are used as triage tools to identify patients
      that require treatment in trauma centres. The Pre-Hospital Index (PHI) is based
      on systolic blood pressure, pulse, respiratory rate, (level of) consciousness,
      and presence of penetrating injury. The present study evaluated the validity and
      internal consistency of the PHI. The study was based on 628 patients assessed by
      physicians at the scene. Mean age was 38.7 years (SD = 24.8), and 65% were male.
      Motor vehicle collisions caused the injury for 45%. The majority had head/neck
      (56%) and extremity (45%) injuries. Mean PHI was 4.62 (SD = 5.77), 40% had a PHI
      of zero, 6% between 1 and 3, 32% between 4 and 7, and 21% greater than 7. The
      associations between PHI and rates of hospital admission, surgery, ICU treatment,
      mortality, duration of hospitalization, and length of ICU stay were significant
      (p < 0.001). A total of 260 (41.4%) patients had major trauma requiring treatment
      at a trauma centre. A PHI > 3 had 83% sensitivity and 67% specificity for
      identifying these patients. Internal consistency of the PHI variables was above
      the acceptable limits. This study has shown that the PHI is a valid and reliable
      physiological measure of injury severity and field triage tool.

PMID- 9006638
TI  - Accident prediction models for roads with minor junctions.
AB  - The purpose of this study was to develop and validate a method for predicting
      expected accidents on main roads with minor junctions where traffic counts on the
      minor approaches are not available. The study was based on data for some 3800 km
      of highway in the U.K. including more than 5000 minor junctions. The highways
      consisted of both single and dual-carriageway roads in urban and rural areas.
      Generalized linear modelling was used to develop regression estimates of expected
      accidents for six highway categories and an empirical Bayes procedure was used to
      improve these estimates by combining them with accident counts. Accidents on
      highway sections were shown to be a non-linear function of exposure and minor
      junction frequency. For the purposes of estimating expected accidents, while the
      regression model estimates were shown to be preferable to accident counts, the
      best results were obtained using the empirical Bayes method. The latter was the
      only method that produced unbiased estimates of expected accidents for high-risk
      sites.

PMID- 9006639
TI  - The impact of work practices on fatigue in long distance truck drivers.
AB  - Twenty seven professional truck drivers completed a 12 hour, 900 km trip under
      each of three driving regimes-a relay (staged) trip, a working hours regulated
      one-way (single) trip, and a one-way (flexible) trip with no working hours
      constraints. The results indicated that none of the driving regimes prevented
      fatigue and that the pattern of fatigue experienced during the trips appeared to
      be related to pretrip fatigue levels.

PMID- 9006640
TI  - Are lower legal blood alcohol limits and a combination of sanctions desirable in
      reducing drunken driver-involved traffic fatalities and traffic accidents?
AB  - In 1970 and 1978, a set of strict new countermeasures against drunk driving went
      in to effect in Japan. Analysis of official statistics of motor vehicle fatality
      data have indicated that alcohol involvement in fatal crashes has declined
      substantially in Japan since 1970. From the beginning of 1970 to the late 1980s
      and 1990s, public awareness of and tolerance for the problem of alcohol-impaired
      driving changed dramatically, as shown in this study. Further it seems that
      attitudes in Japan on drink driving have improved over the last 20 years or so,
      instep with a major program of government action. As well as being part of a long
      running campaign to reduce alcohol related road deaths and injuries, these
      accident savings are an important part of a national strategy which began in
      1970, comprising a well structured legislative program introducing a lower legal
      limit, progressive penalties for those above the legal limit, over and above
      Police enforcement strategies underpinning the law and reinforcing the publicity
      massage. Enactment of the lower legal blood alcohol level with a combination of
      other severe sanctions is desirable for prevention of alcohol-related traffic
      casualties, DWI, and accidents, which is shown in this study. Finally, much of
      the current reduction in alcohol-related fatalities and morbidity reflects that
      Japanese society has largely endorsed alcohol impaired driving as a socially
      undesirable behavior. However, this study suggests that it is necessary for
      policy makers to understand that the DUI problem in Japan must be handled with
      diverse approaches, rather than relying exclusively on the deterrence based laws.

PMID- 9006641
TI  - Trams--a risk factor for pedestrians.
AB  - In Gothenburg tram injuries were identified to be an important cause of traffic
      injuries and fatalities (48%) among pedestrians. During the summer middle-aged
      men, often under the influence of alcohol, were often severely injured and the
      injury rate was also high during the autumn. A majority (60%) of those fatally
      injured were under the influence of alcohol. Most injury events happened at or
      near a tram stop. The most serious injuries arose when the victim landed under a
      tram. In 1992, a runaway tram caused a major disaster, killing 10 pedestrians and
      injuring 30. The injury reducing measures the tram company has now started to
      introduce include safety railings at tram stops, side barriers on the tramcars to
      prevent people from falling under the tram and lower speeds near tram stops.

PMID- 9006642
TI  - Predicting the severity of motor vehicle accident injuries using models of
      ordered multiple choice.
AB  - This paper presents statistical evidence showing how variations in the attributes
      of road users can lead to variations in the probabilities of sustaining different
      levels of injury in motor vehicle accidents. Data from New South Wales,
      Australia, is used to estimate two models of multiple choice which are reasonably
      commonplace in the econometrics literature: the ordered logit model and the
      ordered probit model. Our estimated parameters are significantly different from
      zero at small levels of significance and have signs which are consistent with our
      prior beliefs. As a benchmark for comparison, we consider the risks faced by a 33
      year-old male driver of a 10-year-old motor vehicle who is involved in a head-on
      collision while travelling at 42 kilometres per hour. We estimate that this
      benchmark victim will remain uninjured with a probability of almost zero, will
      require treatment from a medical officer with a probability of approximately 0.7,
      will be admitted to hospital with a probability of approximately 0.3, and will be
      killed with a probability of almost zero. We find that increases in the age of
      the victim and vehicle speed lead to slight increases in the probabilities of
      serious injury and death. Other factors which have a similar or greater effect on
      the probabilities of different types of injury include seating position, blood
      alcohol level, vehicle type, vehicle make and type of collision.

PMID- 9006643
TI  - Alcohol-related predictors of adolescent driving: gender differences in crashes
      and offenses.
AB  - Demographic and alcohol-related data collected from eight-grade students (age 13
      years) were used in logistic regression to predict subsequent first-year driving
      crashes and offenses (age 17 years). For young men's crashes and offenses, good
      fitting models used living situation (both parents or not), parents' attitude
      about teen drinking (negative or neutral), and the interaction term. Young men
      who lived with both parents and reported negative parental attitudes regarding
      teen drinking were less likely to have crashes and offenses. For young women's
      crashes, a good-fitting model included friends' involvement with alcohol. Young
      women who reported that their friends were not involved with alcohol were least
      likely to have crashes. No model predicting young women's offenses emerged.

PMID- 9006644
TI  - What do Israeli Jewish and Arab adolescents know about drinking and driving?
AB  - This article describes a study, which is the first in Israel to investigate
      knowledge concerning drinking and driving among a large group of 2408 adolescents
      of four religions in the north of Israel, in the winter of 1995. The article
      analyses the results by referring to general scores and to five areas in the
      "drinking and driving" domain: legal blood alcohol concentration (BAC) limit,
      minimal number of drinks prohibited by the law before driving, common myths, main
      effects of alcohol on driving ability and youth vulnerability. The article
      emphasizes differences between the Jewish group and the non-Jewish (Arab) group.
      The average score of the sample was 2.06 (out of 5). Jews received the highest
      score (2.30) and Moslems got the lowest score (1.45). No differences were found
      among those who had a driving license and those who had not, and between the
      group of respondents from the north of Israel and a sample of participants from
      the center of the country. Lack of knowledge was revealed especially concerning
      knowledge about the BAC limit and youth vulnerability. Arabs tended to exaggerate
      the amount of drinks allowed to be consumed before driving according to the law,
      to hold common myths more than Jews and to get lower scores concerning alcohol
      main effects on driving skills. However, they tended to be more aware than Jews
      to youth vulnerability.

PMID- 9006645
TI  - The use of feedback signs to increase observed daytime seat belt use in two
      cities in North Carolina.
AB  - Well publicized enforcement programs in North Carolina have raised seat belt use
      to about 80%. In an effort to find techniques to raise belt use further, signs
      providing feedback to drivers on belt use rates were introduced in two
      communities, Asheboro (population 18,000) and Greensboro (population 183,000).
      Feedback signs remind motorists about belt use and imply a constant and vigorous
      enforcement presence. The signs were prominently posted by the roadside at high
      volume locations; belt use information was changed weekly based on observational
      surveys. Observed daytime driver belt use in Asheboro increased from an average
      of 75% before the signs to 89% after the signs were established. At urban sites
      in Greensboro, driver belt use increased from 80% to 86%. Right front passenger
      belt use increased significantly in Asheboro but not in Greensboro. There were no
      changes in belt use at two interstate exit sites in Greensboro. Reasons for the
      differential success rates may relate to differences in initial belt use rates,
      community size, amount of publicity, and numbers of encounters with the signs. It
      is clear, however, that feedback signs can be an important supplement to belt use
      enforcement programs.

PMID- 9006646
TI  - Injuries and use of protective equipment among college in-line skaters.
AB  - In-line skating injuries and protective gear use were explored in a sample of
      college students (n = 217). A minority of respondents wore protective gear. One
      third of skaters had experienced at least one minor injury, and a smaller
      percentage had experienced fractures or head injuries. Most minor injuries
      occurred during the first 1-2 times skating, while more serious injuries tended
      to occur after at least 50 times on in-line skates. Psychosocial predictors of
      protective gear use were explored. Four major Health Belief Model constructs
      (perceived barriers to wearing gear, perceived susceptibility to injury,
      perceived severity of injury, and perceived benefits of wearing gear) were
      significant predictors of protective gear use. The Health Belief Model, tested
      using regression and structural equation modelling, predicted gear typically
      worn, frequency of gear use, and injuries received while in-line skating.
      Implications for increasing protective gear use are described.

PMID- 9006647
TI  - Conflicting goals of skid training.
AB  - Efforts to make novice drivers drive more safely on slippery roads by means of
      special courses have mainly failed. In order to understand why the courses have
      failed, the views of instructors and students on the goals of skid training
      courses were compared. The importance given to anticipating vs manoeuvring skills
      was analysed. After completing a skid training course, students in four Nordic
      countries (Denmark, Finland, Norway and Sweden) assessed manoeuvring skills to be
      equally important to anticipating skills in the courses. However, instructors
      assessed anticipating skills to be more important than manoeuvring skills. The
      differences between the assessments of instructors and students were the same in
      all four countries. Manoeuvring exercises are widely used in the courses although
      the main purpose of these courses is to develop anticipating skills. The
      exercises may give students the impression that manoeuvring skills are more
      important than anticipating skills. Manoeuvring exercises also increase their
      self-confidence and may lead to underestimation of the risks involved, resulting
      in e.g. driving at higher speed.

PMID- 9006648
TI  - Further aspects of the British index of secondary car safety.
AB  - This paper develops earlier research into statistical methods for comparing the
      secondary safety of car models. Two papers (Broughton 1996a,b, Accident Analysis
      and Prevention, Vol. 28, pp. 89-99, and pp. 101-109, respectively) had concluded
      that the most satisfactory index of secondary safety is the one first used in
      publications of the U.K. Department of Transport, referred to as the British or
      DoT index. This paper shows that the distribution of the risk of injury when two
      cars collide depends principally on the difference in mass; as this rises, the
      driver of the lighter car is more likely to be injured and the driver of the
      heavier car is less likely to be injured, while the likelihood of both being
      injured reduces slightly. It also shows that the level of protection in fatal and
      serious accidents varies between models to a significantly greater extent than
      the level in all injury accidents. Car models of similar mass can provide
      significantly different levels of protection to their occupants, so there would
      be fewer casualties if all models were to provide the same level of protection as
      the most successful current designs. It is estimated that if the safety of all
      models were improved to the level achieved or exceeded by the safest twentieth of
      models then the number of drivers injured in two-car accidents would fall by 12%
      and the number killed or seriously injured by 22%.

PMID- 9006649
TI  - Comment on Williams and Farmer's evaluation of daytime running lights.

PMID- 9006650
TI  - The lateral corticospinal tract and spinal ventral horn in X-linked recessive
      spinal and bulbar muscular atrophy: a quantitative study.
AB  - A quantitative study was performed on spinal cord lesions in seven patients with
      X-linked recessive spinal and bulbar muscular atrophy. The myelinated fiber
      density of the lateral corticospinal tracts at the T7 cord level was well
      preserved for both large and small myelinated fibers. On the other hand, neurons
      in the L4 ventral horn were markedly depleted; marked loss was noted of the large
      alpha and medium-sized gamma motor neurons located in the lateral and medial
      nuclei as well as the small neurons in the intermediate zones of the ventral
      horn. These results suggest that myelinated fiber density and fiber-size
      distribution in the corticospinal tract are well preserved and that neuronal loss
      in the ventral horns is not restricted to alpha and gamma motoneurons but also
      involves small interneurons.

PMID- 9006652
TI  - Traumatic spinal cord injury: a neuropathological study on the longitudinal
      spreading of the lesions.
AB  - Eight patients died after traumatic spinal cord injuries. At autopsy,
      neuropathological examination revealed longitudinal spreading of cord lesions in
      two of these patients. One developed progressive paralysis 43 h after fracture of
      the fifth cervical (C5) vertebra and died 38 days after injury. Necrotic lesions
      extended upward to the medulla oblongata and downward to the C7 cord segment.
      Pencil-shaped necrosis (C7-T4) and marginal spongiosis (C7-T2) were also found. A
      second patient died 5 months after C5 subluxation with tetraplegia. His spinal
      cord was severely compressed at C4/5 and pencil-shaped necrosis, which had become
      partially cystic, extended upward to C3 and downward to T1; marginal spongiosis
      was also found in C4-C5. In both cases, complete necrosis without cell reaction
      was found in several cord segments, including the initially impacted segment.
      These findings suggest that intra- and extramedullary circulatory impairment
      occurred not only at the initial impact level, but also in the adjacent levels.
      Increased intramedullary pressure, resulting from this circulatory disturbance,
      in combination with a narrowed spinal canal, may induce the upward and downward
      spreading of the lesion.

PMID- 9006651
TI  - Neurofibrillary tangles in the dentate granule cells of patients with Alzheimer's
      disease, Lewy body disease and progressive supranuclear palsy.
AB  - Recent studies have shown that the dentate granular cells of the hippocampus are
      affected in patients with Alzheimer's disease (AD). To gain a better
      understanding of the cytoskeletal alterations in these cells, we carried out
      immunocytochemical and immunoelectron microscopic analysis of the dentate gyrus
      of patients with primary degenerative dementias, using a monoclonal antibody
      against paired helical filaments (TG3). This antibody labeled a large number of
      spherical inclusions in the dentate granule cells of patients with AD and its
      Lewy body variant (LBV). These inclusions consisted of straight tubular
      structures (about 18-25 nm in diameter), similar to those found in progressive
      supranuclear palsy (PSP). These inclusions, although in a smaller number, were
      also found in demented patients with PSP, but not in those with diffuse Lewy body
      disease or age-matched controls. These findings indicate that the neurofibrillary
      alterations in the dentate granule cells of patients with AD, LBV and PSP share
      cytoskeletal similarities.

PMID- 9006653
TI  - Superoxide dismutase-like immunoreactivity in spheroids in Hallervorden-Spatz
      disease.
AB  - Iron accumulation in the basal ganglia and spheroid formation are pathological
      hallmarks of Hallervorden-Spatz disease (HS). Since an overaccumulation of iron
      (iron thesaurosis) that exceeds the binding capacity of ferritin could cause
      oxidative damage, we studied the possible role of oxidative stress in the
      pathogenesis of HS. The basal ganglia and spinal cord from patients with HS were
      investigated at autopsy, using histochemistry for iron and immunohistochemistry
      for Cu/Zn superoxide dismutase (SOD1), Mn superoxide dismutase (SOD2) and
      ferritin. SOD1-like immunoreactivity (IR), SOD2-IR and ferritin-IR occurred
      frequently in spheroids observed in the basal ganglia, and associated iron
      accumulation indicated the possible existence of increased oxidative stress in HS
      patients. Spheroids in the spinal cord showed intense SOD1-IR and SOD2-IR in HS,
      in sharp contrast with the occasional weak SOD1-IR and SOD2-IR observed in
      spheroids from patients with amyotrophic lateral sclerosis (ALS). Neither
      increased ferritin-IR nor iron accumulation were observed in spinal spheroids
      from HS and ALS patients. These data may suggest that, at least in the spinal
      cord, SOD1-IR and SOD2-IR in spheroids in HS patients do not result from
      oxidative stress directly related to iron accumulation.

PMID- 9006654
TI  - Early-infantile galactosialidosis with multiple brain infarctions: morphological,
      neuropathological and neurochemical findings.
AB  - Post-mortem morphological, neuropathological and neurochemical findings are
      described in a girl, aged 14 months, with the early-infantile form of
      galactosialidosis. An elevation in non-lipid sialic acid was noted in both the
      grey and white matter of the brain, whereas the white matter displayed a clear
      reduction in all the major lipids. Multiple cortical-subcortical infarctions were
      found in the brain, most probably caused by compromised circulation due to
      endothelial luminal encroachment. Electron microscopy of cerebral blood vessels
      revealed major swelling of the endothelium due to prominent cytoplasmic
      vacuolisation. Multiple cytoplasmic vacuoles containing sparse granular or
      membranous matter were also seen in neurons and glial cells of the brain and
      spinal cord. Zebra bodies were found in the Purkinje cells, as well as in the
      spinal anterior horn cells. Prominent endothelial vacuolisation was noted in the
      liver and kidneys. The renal vascular encroachment was probably the cause of the
      arterial hypertension with elevated plasma renin activity in the present case.
      There were innumerable fine vacuoles in the renal epithelium and in the Kupffer
      cell of the liver, whereas coarser vacuoles were observed in the hepatocytes. The
      neuronal ultrastructural findings in the present case bear some resemblance to
      the few reported cases of late-infantile and adult cases of galactosialidosis.
      The prominent endothelial vacuolisation and focal cerebrovascular lesions, that
      have not previously been described in galactosialidosis, may be features specific
      to the rapidly progressive early-infantile form.

PMID- 9006655
TI  - Immunogold and freeze etch electron microscopic studies of merosin localization
      in basal lamina of human skeletal muscle fibers.
AB  - Merosin is a basement-membrane-associated protein found in striated muscle,
      peripheral nerve and placenta, the deficiency of which causes the muscle wasting
      condition in C57BL/6J-dy/dy, so-called dy/dy mouse. Moreover, merosin is the
      binding protein of 156 kDa alpha-dystroglycan which binds dystrophin by way of 43
      kDa beta-dystroglycan. Therefore, merosin is an important component of the basal
      lamina of normal skeletal myofibers. We investigated the ultrastructural
      localization of merosin antibody in normal human skeletal myofibers by using
      immunogold electron microscopy and freeze etch electron microscopy. The
      ultrastructure of the basal lamina showed the presence of the lamina lucida,
      lamina densa and lamina reticularis. The lamina lucida appeared electron
      translucent with the exception of fuzzy fibrils. The immunogold electron
      microscopy disclosed that the merosin was present at the innermost layer (lamina
      lucida) of the basal lamina of normal human skeletal myofibers. With freeze etch
      replica electron microscopy, short cross-bridge fine fibrils were noted in the
      lamina lucida, connecting the basal lamina to the outer leaflet of the muscle
      plasma membrane. They measured 3-13 nm in diameter, 20-90 nm in length and were
      distributed with a spacing of 30-40 nm. The immunogold particles showing the
      presence of the merosin epitope were associated with these connecting structures.

PMID- 9006656
TI  - Characterization of spherical amyloid protein from a prolactin-producing
      pituitary adenoma.
AB  - Prolactin (PRL)-producing pituitary adenomas are in some cases associated with
      deposition of abundant spherical amyloid; however, the origin of the amyloid has
      not been established. In this report, a PRL-producing pituitary adenoma composed
      almost entirely of spherical amyloid was analyzed biochemically. The tumor was
      removed surgically from a 56-year-old man. Immunohistochemical analysis revealed
      that residual tumor cells were strongly positive for PRL, while the spherical
      amyloid was not. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      revealed a band of approximately 4 kDa associated with the amyloid, which was not
      present in a nonamyloid producing prolactinoma. The 4-kDa band is similar in size
      to other known amyloidogenic peptides. Immunoblot analysis of the tumor material
      using polyclonal anti-human PRL antibodies revealed a small amount of normal
      sized PRL; however, the abundant 4-kDa band was nonimmunoreactive. Amino acid
      sequencing showed that this peptide represents the first 34 amino acids of the
      intact PRL protein with a predicted size of 4313 Da. The presence of a small
      amount of normal-sized PRL in this tumor, as well as elevated circulating levels
      of PRL implies that intact PRL is being abnormally processed in the formation of
      spherical amyloid.

PMID- 9006657
TI  - Morphological study of neocortical areas in Rett syndrome.
AB  - Various neocortical areas from four females aged 16-24 years with Rett syndrome
      (RS) were investigated and compared with brains of therapy-resistant partial
      epilepsy (TRPE) patients (18-25 years), infantile autism (IA), and control brains
      (24 and 58 years). The cytoarchitecture of area 10 (frontal), area 21 (temporal),
      area 4 (primary motor cortex), and area 17 (primary visual cortex) was studied by
      the combined Kluver-Barrera (luxol fast blue and cresyl violet) standard
      procedure. Autofluorescence of lipofuscin, immunofluorescence of synaptic vesicle
      proteins [synaptophysin (p38)] and lectin-stained (Wisteria floribunda
      agglutinin) perineuronal nets (PNs) were studied in the cortices using dual
      channel confocal laser scanning microscopy. The brains of RS females show various
      types of morphological/cytoarchitectonical abnormalities of single pyramidal
      neurons in layers II-III, and V-VII of different cortical areas. The
      abnormalities include mild losses of pyramidal neurons, more pronounced in layers
      II and III than in layers V and VII, and more evident in frontal and temporal
      areas than in the visual cortex. Microdysgenesis, including abnormalities due to
      neuronal migration disorders, was not found in RS, in contrast to the
      observations in TRPE patients, strongly indicating that RS is not a neuronal
      migration disorder. Lipofuscin distribution was normal but amounts were lower in
      RS cases than in control and TRPE brains. PNs were less expressed in cortices of
      the IA case but were clearly overexpressed in the motor cortex of RS.
      Quantitative analysis of p38 showed a decrease in the area occupied by p38
      immunoreactivity by 20-40% in RS compared with controls. It is concluded that RS
      could best be explained by a postnatal synaptogenic developmental deficiency; the
      basic defect, however, is still completely unknown.

PMID- 9006659
TI  - Changes of cytoskeletal protein immunostaining in myelinated fibre tracts after
      focal cerebral ischaemia in the rat.
AB  - Breakdown of the cytoskeleton has been proposed to be a central event in the
      evolution of ischaemic brain damage. Alterations in the immunostaining of
      cytoskeletal proteins, particularly microtubule-associated protein (MAP) 2, have
      been suggested to be sensitive markers of ischaemic damage in the somatodendritic
      compartment. However, axons are also subjected to the adverse conditions created
      by an ischaemic challenge, but MAP2 is not located in the axonal compartment. The
      purpose of the present study was to examine immunostaining of beta-tubulin, MAP1a
      and MAP5, all of which are located in axons as well as perikarya, specifically in
      myelinated fibre tracts in rats subjected to unilateral middle cerebral artery
      (MCA) occlusion. In sham-operated control rats immunostaining of all three
      antibodies in myelinated fibre tracts had a smooth, regular appearance. Two hours
      after MCA occlusion there were striking changes in the patterns of immunostaining
      of all three antibodies in myelinated fibre tracts within the MCA territory.
      These were particularly noticeable in beta-tubulin- and MAP5-stained sections
      where the pattern in white matter had a rough, globular appearance. This pattern
      was accentuated at 6 h after MCA occlusion and the presence of "bulb-like"
      profiles in white matter tracts was notable particularly in the MAP5-stained
      sections. Thus, the changes in the patterns of staining at 2 h after MCA
      occlusion may represent the early stages of axonal disconnection, and
      immunostaining of microtubular proteins may represent a sensitive method to
      assess ischaemically induced damage to myelinated fibre tracts.

PMID- 9006658
TI  - Chronic constriction model of rat sciatic nerve: nerve blood flow, morphologic
      and biochemical alterations.
AB  - We evaluated the nerve blood flow (NBF), light and electron microscopy, and
      adrenergic innervation of rat sciatic nerve at 2-45 days after the application of
      four loose ligatures. Ischemia developed at the lesion edge, creating an
      endoneurial dam. Calcitonin gene-related peptide, norepinephrine and NBF were
      increased within the lesion. Morphologic alterations consisted of early
      endoneurial edema, followed by myelinated fiber degeneration, with relative
      sparing of small myelinated and unmyelinated nerve fibers, and leukocyte adhesion
      to microvessels. Axonal degeneration predominated over demyelination. At 45 days,
      profuse regeneration of small myelinated fibers was seen. The mechanism of
      lesional sensitization is discussed.

PMID- 9006660
TI  - Effects of an intratumoral injection of human recombinant tumor necrosis factor
      alpha on cerebrovascular permeability and leukocytic infiltration in a rat glioma
      model.
AB  - The pro-inflammatory and blood-brain barrier (BBB) effects of intratumoral (IT)
      injection of human recombinant tumor necrosis factor-alpha (rTNF-alpha) were
      studied in the Fischer rat RT-2 glioma model. Animals received a single
      stereotaxic injection of either 6 x 10(4) U rTNF-alpha or excipient (vehicle)
      into the center of an intracerebrally implanted glioma. In order to demonstrate
      any effects rTNF-alpha might have on the BBB, studies were conducted using
      endogenous IgG (150 kD) as a tracer. Forty-eight hours following injection of
      excipient, a margin of peritumoral IgG extravasation was observed while rats
      treated with 6 x 10(4) U rTNF-alpha showed a dense and extensive IgG
      extravasation involving both hemispheres. Histological examination revealed that
      an IT rTNF-alpha injection induced leukocytic adherence, neutrophilic cuffing and
      infiltration throughout the lesion from 12 to 72 h after injection. These
      histological observations were supported by quantification of cerebral
      myeloperoxidase (MPO) levels which indicated a significant increase in
      neutrophils over the excipient recipients at 4 and 12 h. These MPO levels
      contrasted with our earlier studies in normal rats which revealed no significant
      difference in tissue MPO levels following injection of excipient or rTNF-alpha.
      In addition, when MPO levels in tumor models and normal rats receiving TNF were
      compared, a significantly greater presence of neutrophils was seen in tumor
      models at 12 h post-TNF injection. We believe that the increased inflammatory
      response seen in a progressing glioma compared to normal brain may be the result
      of decreased resistance to leukocytic infiltration due to increased vascular
      surface area, the lack of infiltration-resistant perivascular basement membrane,
      and/or increased extracellular space.

PMID- 9006661
TI  - Amyloid P immunoreactivity precedes C4d deposition on extracellular
      neurofibrillary tangles.
AB  - Extracellular neurofibrillary tangles (eNFTs) are the insoluble cytoskeletal
      debris left behind when neurons with intracellular neurofibrillary tangles
      (iNFTs) die. Reactive microglia and reactive astrocytes gather around eNFTs. Many
      inflammatory proteins are deposited in their vicinity, including activated
      components of the classical complement pathway. Agents which are potential
      activators of the pathway include beta-amyloid protein (A beta) and amyloid P
      (AP), since these in vitro activators have been reported to be associated with
      both senile plaques (SPs) and eNFTs. To investigate the apparent order in which
      these proteins are deposited, we studied by immunohistochemistry the relative
      association of AP, A beta, and the classical complement protein C4d with eNFTs in
      Alzheimer's disease (AD), parkinsonism-dementia complex of Guam (lytico-bodig,
      LB), and elderly non-demented cases. In normal elderly cases with mild tangle
      development, most but not all eNFTs were AP positive. Substantially fewer eNFTs
      were C4d positive, and in two of the three cases no eNFTs were A beta positive.
      In AD and mild LB cases with more extensive tangle development, a high portion of
      eNFTs were AP positive, and most of them were C4d positive. Only a few were A
      beta positive. In severe LB cases, with dense tangle development, almost all
      eNFTs were AP and C4d positive, and a significant number were also A beta
      positive. AP seems to be deposited early in eNFT exposure and could therefore be
      a potential activator of the complement pathway, while A beta deposition occurs
      relatively late in the process, and is therefore unlikely to be responsible.

PMID- 9006663
TI  - Leser-Trelat sign with anaplastic ependymoma--an autopsy case.
AB  - A 36-year-old Japanese male, who 7 years previously had been diagnosed as having
      an ependymoma in the left parietal region, had received surgery, chemotherapy and
      radiotherapy. He later developed a rapid growth of multiple skin lesions on his
      back and extremities, which coincided with a regrowth of the tumor. Postmortem
      examination revealed that the ependymoma showed anaplastic transformation and
      necrosis; however, no malignancy was observed in the extracranial organs. The
      skin lesions were histologically diagnosed as seborrheic keratoses. We have,
      therefore, diagnosed the patient as having Leser-Trelat sign associated with
      anaplastic ependymoma.

PMID- 9006662
TI  - Tuberous sclerosis-like lesions in epileptogenic human neocortex lack allelic
      loss at the TSC1 and TSC2 regions.
AB  - Glioneuronal malformations with a striking histological resemblance to cortical
      tubers of tuberous sclerosis, but no extracerebral stigmata of this phacomatosis,
      are frequently encountered in patients with chronic pharmacoresistant epilepsies.
      It is controversial as to whether these lesion represent a forme fruste of
      tuberous sclerosis or a distinct entity. The recently reported loss of
      heterozygosity (LOH) at the regions of the TSC1 or TSC2 locus in hamartomas
      obtained from different organs of patients with established tuberous sclerosis,
      including cortical tubers, stimulated us to examine epilepsy-associated tuberous
      sclerosis-like glioneuronal malformations with respect to LOH at the TSC1 and
      TSC2 loci of chromosomes 9q34 and 16p 13.3, respectively. The analysis was
      carried out on DNA derived from paraffin-embedded brain tissues of 11 patients.
      For 5 patients, peripheral blood leukocytes were also available for DNA
      extraction. We performed microsatellite analysis with five markers on chromosome
      9 and four markers on chromosome 16. In addition, polymerase chain reaction
      restriction fragment length polymorphism (RFLP) analysis was performed using a
      polymorphic EcoRV restriction site in exon 40 of the TSC2 gene. No LOH was
      identified in any of the cases. These findings do not support a relationship
      between the epilepsy-associated glioneuronal lesions and tuberous sclerosis.
      However, tuberous sclerosis is genetically heterogeneous and microsatellite and
      RFLP analysis cannot exclude small deletions or point mutations. Thus, given the
      histopathological similarity of glioneuronal malformations in epilepsy patients
      to cortical tubers, further molecular genetic studies will be needed as our
      understanding of the molecular basis of tuberous sclerosis increases to
      completely clarify the relationship of these lesions to tuberous sclerosis.

PMID- 9006665
TI  - Regulation of managed care incentive payments to physicians.

PMID- 9006664
TI  - Fatal reaction from inadvertent intrathecal entry of ionic contrast medium during
      a nephrogram.
AB  - A fatal case of inadvertent intrathecal entry of an ionic contrast medium during
      a nephrogram is reported. The patient developed seizures and failed to regain
      consciousness following the event. Computerized tomography revealed extensive
      intraventricular and subarachnoid hyperdensity and cerebrospinal fluid analysis
      revealed markedly elevated protein content. At autopsy a traumatic communication
      between the kidney and thecal sac was identified. Histopathological examination
      revealed cytoplasmic shrinkage and eosinophilia, nuclear pyknosis and
      karyorrhexis in neocortical neurons. Central chromatolysis was seen in brain stem
      motor nuclei and anterior horn cell neurons. The neuropathological findings
      appear to be on the basis of direct neurotoxicity from the contrast medium and
      excitotoxic injury secondary to seizure activity. Inadvertent intrathecal
      administration of ionic contrast media is a rare occurrence with often fatal
      consequences despite aggressive medical management.

PMID- 9006666
TI  - The legal and ethical implications of gag clauses in physician contracts.

PMID- 9006668
TI  - Unresolved issues in controlling the tuberculosis epidemic among the foreign-born
      in the United States.

PMID- 9006667
TI  - The private insurance industry's tactics against suspected homosexuals: redlining
      based on occupation, residence and marital status.

PMID- 9006669
TI  - Trav'lin' light: early retirees and the availability of post-retirement health
      benefits.

PMID- 9006670
TI  - Role of arachidonic acid metabolites in tumor growth inhibition by nonsteroidal
      antiinflammatory drugs.
AB  - PURPOSE: A murine model of squamous cell carcinoma (SCC) was used to determine
      the role of arachidonic acid (AA) metabolites in the growth of SCC of the head
      and neck. MATERIALS AND METHODS: C3H/HeJ mice bearing SCC (SCC VII) were treated
      with cyclooxygenase inhibitors (piroxicam and nabumetone) or a 5-lipoxygenase
      inhibitor (ketoconazole). Growth curves were established, and final tumor weights
      were measured. Following sacrifice, tumor tissue homogenates were assayed for
      prostaglandin E2 (PGE2) and 12-hydroxyeicosatetraenoic acid (12-HETE) by enzyme
      linked immunosorbent assay (ELISA), and leukotriene B4 (LTB4) by radioimmunoassay
      (RIA). Inflammatory cell infiltrate was assessed histologically. RESULTS: A
      significant inhibition of tumor growth (P = .001) and final tumor weight (P =
      .002) was noted in mice treated with piroxicam and nabumetone. Inhibition of
      tumor growth was associated with increased tumor tissue levels of PGE2 (P = .04)
      and lymphocytic infiltration (P = .07). Significant inhibition of tumor growth (P
      = .002) and final tumor weight (P = .05) was also noted in mice treated with
      ketoconazole. CONCLUSION: These data suggest that both cyclooxygenase and
      lipoxygenase metabolites of AA affect tumor growth in this model and that
      inhibition of tumor growth by inhibitors of AA metabolism may be caused by an
      enhanced inflammatory cell response at the tumor site.

PMID- 9006673
TI  - Success in surgery for otosclerosis: hearing improvement and other indicators.
AB  - PURPOSE: This retrospective study investigates the general outcome and subjective
      impression of patients who have undergone surgery for otosclerosis. Postoperative
      complaints and complications, as well as hearing results, are also reported.
      MATERIALS AND METHODS: Questionnaire and audiomeric results of 246 stapes surgery
      patients (270 operations) were studied. RESULTS: Hearing results showed a mean
      improvement in pure-tone average of 26 dB and air-bone gap closure to within 10
      dB in 214 cases (79%). No serious complications or profound sensorineural hearing
      loss occurred. Patients were generally pleased with surgery, and subjective
      evaluation of benefit corresponded with objective audiometric result. However, a
      variety of complaints, such as vertigo, tinnitus, loud noise intolerance, pain,
      chorda tympani symptoms, and sound distortion problems, were reported. Most of
      these symptoms correlated significantly with the patients' subjective opinion of
      the surgical outcome. CONCLUSION: Patients as well as surgeons consider hearing
      improvement as the main indicator of success in surgery for otosclerosis.
      However, postoperative symptoms and complaints can be expected in a certain
      percentage of patients. Because these can influence the general outcome of
      surgery, the ear surgeon should try to painstakingly refine his technique in an
      effort to minimize their sources. They should also be discussed in preoperative
      patient counseling.

PMID- 9006672
TI  - Osteomyelitis of the base of the skull secondary to Aspergillus.

PMID- 9006674
TI  - Objective and subjective nasal airflow.
AB  - PURPOSE: This study was designed to assess whether a correlation exists between
      the rhinomanometric measurement of nasal resistance, nasal airflow, and the
      subjective sensation of airflow. MATERIALS AND METHODS: Sixteen patients with
      recurrent maxillary sinusitis were examined before and after uncinectomy during
      functional endoscopic sinus surgery. Subjective nasal sensation of airflow was
      assessed by means of a visual scale before and after uncinectomy. Rhinomanometry
      was performed three times for every patient: before anesthesia, and before and
      after uncinectomy. The subjective nasal sensation of airflow was compared with
      the nasal airflow and resistance to flow as measured by rhinomanometry. RESULTS:
      Rhinomanometric measurements were almost the same before and after uncinectomy,
      with no significant difference, whereas patients reported a significant
      improvement in nasal airflow. CONCLUSION: Rhinomanometric measurements of nasal
      airflow and resistance often have no correlation to the patients's sensation of
      airflow. However, because it is the patients' ultimate concern to breathe more
      comfortably, the rhinomanometer has little clinical value.

PMID- 9006671
TI  - Evaluation of bilateral vocal fold dysfunction: paralysis versus fixation,
      superior versus recurrent, and distal versus proximal to the laryngeal nerves.

PMID- 9006675
TI  - Use of an implantable hearing device.
AB  - PURPOSE: The purpose of this paper was to discuss our experiences with an
      implantable bone conduction hearing prosthesis, the XOMED Audiant Bone Conductor
      (Jacksonville, FL). PATIENTS AND METHODS: Twenty-four patients who had been
      implanted with the Audiant Bone Conductor were interviewed by telephone following
      implantation. Questions were asked regarding use of the device and subjective
      benefit. RESULTS: Eleven patients are using their devices, 12 patients are not
      using their devices, and one patient has been lost to follow-up. Patients using
      the device report satisfaction and prefer the Audiant to other amplification
      systems, whereas those not using the device indicate that insufficient
      amplification or weak magnetic attraction prevent its use. CONCLUSIONS: Analysis
      of failures has altered our criteria for implantation. With improvements that
      have been made by XOMED and stricter patient criteria, the Audiant should be
      considered a viable amplification alternative for certain hearing-impaired
      patients.

PMID- 9006676
TI  - Identification and assessment of velopharyngeal inadequacy.
AB  - PURPOSE: To review current literature with respect to the diagnosis and
      assessment of velopharyngeal inadequacy (VPI), including present knowledge about
      the most common causes of VPI. METHODS: Data sources include published reports
      over the past 20 years derived from computerized databases and bibliographies of
      pertinent articles and books. Indexing terms used were "velopharyngeal
      incompetence," "velopharyngeal inadequacy." "velopharyngeal insufficiency."
      CONCLUSION: VPI is most commonly associated with cleft palate, submucous cleft
      palate, and following adenoidectomy. The otolaryngologist can prevent the latter
      by preoperative identification of physical stigmata associated with VPI.
      Perceptual assessment is the criterion standard for diagnosis of VPI. Multiview
      videofluorography and flexible nasal endoscopy provide the best direct
      assessments to help plan and direct the optimal treatment of VPI.

PMID- 9006677
TI  - Superior mediastinal dissection in the treatment of Hurthle cell carcinoma of the
      thyroid.
AB  - BACKGROUND: Hurthle cell carcinoma of the thyroid frequently metastasizes to
      regional lymph nodes. Delayed lymph node dissection may become necessary, adding
      little risk to patient survivability; however, metastatic disease to the superior
      mediastinum that cannot be promptly detected, represents a survival threat that
      deserves special attention. The purpose of this study is to review our experience
      in managing Hurthle cell carcinoma of the thyroid and make recommendations for
      appropriate treatment. PATIENTS AND METHODS: A retrospective review of 371
      thyroid neoplasms seen between 1987 and 1994 yielded six patients with Hurthle
      cell carcinoma of the thyroid gland. These include three cases treated with
      thyroidectomy and transcervical superior mediastinal dissection (SMD) as initial
      treatment and three cases treated with thyroidectomy alone. RESULTS: Of the three
      patients treated with SMD as part of their initial treatment, one had occult
      micrometastases to the superior mediastinum. All three patients remain alive and
      disease free at least 3 years later, whereas all three patients treated with
      thyroidectomy alone developed superior mediastinal metastases and died of their
      disease. CONCLUSION: We propose that at the time of initial surgery, a
      transcervical SMD may prevent spread to the superior mediastinum and therefore,
      improve survivability.

PMID- 9006678
TI  - Sebaceous gland carcinoma: report of a case and review of literature.

PMID- 9006680
TI  - Hiatal hernia and reflux complicating prosthetic speech.

PMID- 9006679
TI  - A review of Merkel cell carcinoma with emphasis on lymph node disease in the
      absence of a primary site.

PMID- 9006681
TI  - Asymptomatic high jugular bulb in the pediatric population.

PMID- 9006682
TI  - Subfrontal schwannoma with intracranial mucocele: a case report.

PMID- 9006683
TI  - Letterer-Siwe disease with bilateral temporal bone involvement.

PMID- 9006684
TI  - Ten-year prognosis of isolated and combined medial collateral ligament ruptures.
      A matched comparison in 40 patients using clinical and radiographic evaluations.
AB  - In a matched-pair study of 40 patients, the prognoses of patients with acute
      isolated partial medial collateral ligament injuries and acute combined medial
      collateral and anterior cruciate ligament injuries were compared 10 years after
      initial treatment. All patients in the first group were treated nonoperatively.
      In the latter group, most medial collateral ligament injuries were total
      ruptures, which were thoroughly repaired; the torn anterior cruciate ligament was
      repaired with augmentation in half of the cases. At the follow-up evaluation,
      both patient groups had similarly high knee functions according to the Lysholm
      score and similar activity levels (recreational team sports). Knees with combined
      injuries had increased sagittal laxity at manual and instrumented assessment.
      Radiographic signs of knee osteoarthritis were present in half of the knees with
      combined injuries, but they were absent in knees with isolated injuries. The long
      term functional prognosis was similarly good after isolated or combined medial
      collateral ligament injuries, but patients with combined ruptures had more
      reinjuries and repeat surgeries, increased sagittal laxity, and a higher
      incidence of radiographic osteoarthritis.

PMID- 9006686
TI  - Traumatic tears of the subscapularis tendon. Clinical diagnosis, magnetic
      resonance imaging findings, and operative treatment.
AB  - The study population consisted of 14 shoulders in 13 consecutive patients with
      surgically confirmed isolated subscapularis tendon tears. In all but three
      patients, the mechanism of injury was traumatic hyperextension or external
      rotation of the abducted arm. All patients reported pain and weakness in the
      affected shoulder. Physical findings revealed limited passive range of motion at
      maximal internal and external rotation due to pain, weakness of internal rotation
      of the shoulder, and tenderness in the region of the intertubercular groove.
      However, these findings did not conclusively point to the subscapularis tendon as
      the site of injury. Preoperative interpretation of magnetic resonance imaging
      studies was used to diagnose tears of the subscapularis tendon in 14 shoulders
      and biceps tendon subluxation or dislocation in 6 shoulders. On arthroscopic
      examination, one patient was found to have a partial-thickness tear that was
      treated with arthroscopic debridement. Six shoulders had full-thickness tears of
      the subscapularis tendon, and seven shoulders had full-thickness tears associated
      with concomitant biceps tendon pathologic conditions, including subluxation,
      dislocation, or rupture. The full-thickness subscapularis tendon tears were
      repaired via an open anterior approach to the shoulder through the deltopectoral
      groove. Associated biceps tendon injuries were treated with tenodesis of the
      tendon to the intertubercular groove. Our early followup results have shown that,
      with proper diagnoses and surgical treatments, patients have greatly decreased
      pain and marked improvement in shoulder function.

PMID- 9006685
TI  - The diagnosis of meniscal tears in athletes. A comparison of clinical and
      magnetic resonance imaging investigations.
AB  - This study evaluated the predictability of clinical examination alone in
      comparison with magnetic resonance imaging in the diagnosis of meniscal tears in
      competitive athletes. Ninety-three competitive athletes were prospectively
      investigated between 1992 and 1995. A total of 57 athletes were operated on based
      on clinical examination alone, and the 36 remaining athletes had magnetic
      resonance imaging before surgery. The correct diagnosis of a meniscal lesion was
      made on clinical examination alone in 83 athletes (89%) and on magnetic resonance
      imaging the correct diagnosis was also made in 89% of 36 athletes. The overall
      values for the clinical investigation of the medial and lateral menisci combined
      were 94.5%, 91.5%, 99%, 96.5%, 87% for accuracy, positive predictive value,
      negative predictive value, sensitivity, and specificity, respectively. The
      overall values for magnetic resonance imaging of the medial and lateral menisci
      combined were 95.5%, 96.5%, 91.5%, 98%, 85.5% for accuracy, positive predictive
      value, negative predictive value, sensitivity, and specificity, respectively.

PMID- 9006687
TI  - Central quadriceps tendon for anterior cruciate ligament reconstruction. Part I:
      Morphometric and biomechanical evaluation.
AB  - We examined the anatomic and biomechanical adequacy of the central quadriceps
      tendon as an alternative graft source for anterior cruciate ligament
      reconstruction. Morphometry was performed on 15 preserved and 6 fresh-frozen
      specimens. Biomechanical testing was performed on the six fresh-frozen specimens.
      We initially used a triple suture through the tendon construction, and then
      clamping directly on the tendon. Morphometry yielded the following measurements:
      length, 6.1 +/- 1.0 cm; width, 2.7 cm (range, 2.1 to 3.7); and thickness, 7 mm
      (range, 6.4 to 7.8). The thickness was 1.8 times that of the patellar tendon.
      Biomechanical testing showed that suture failure occurred at 692 +/- 181 N, and
      tendon failure occurred at 1075 +/- 449 N. The load to tendon failure was 1.36
      times that of a comparable-width patellar tendon graft, although the difference
      was not statistically significant. The failure mode was primarily through partial
      or complete tendinous avulsion, with only one specimen failing at midsubstance.
      These findings show the central quadriceps graft is of sufficient size and
      strength to be used for anterior cruciate ligament reconstruction.

PMID- 9006688
TI  - Quantitative analysis of synovial fibrosis in the infrapatellar fat pad before
      and after anterior cruciate ligament reconstruction.
AB  - We performed quantitative analysis of synovial fibrosis in the infrapatellar fat
      pad in 26 patients who underwent arthroscopically assisted anterior cruciate
      ligament reconstructions. Twelve patients underwent reconstruction with patellar
      tendon autografts, and 14 had reconstructions with semitendinosus and gracilis
      tendon autografts. Synovial samples were obtained at the time of reconstruction
      from 10 patients and at second-look arthroscopy from all 26 patients. Sections
      from quick-frozen samples were stained with either hematoxylin and eosin or Fast
      green and Sirius red. We used sodium hydroxide in absolute methanol to elute the
      Fast green and Sirius red stains, and the total collagen content of each section
      was estimated by measuring the optical density of the eluted solution. The volume
      of each section was determined on a computer using an imaging program, and
      collagen content per unit of tissue was calculated. Median collagen content was
      15.3 micrograms/mm3 for the preoperative samples, 25.1 micrograms/mm3 for the
      group with patellar tendon autografts, and 27.1 micrograms/mm3 for the group with
      hamstring tendons autografts. Analysis of preoperative and postoperative paired
      samples revealed a significant increase in synovial collagen after anterior
      cruciate ligament reconstruction. We observed increased fibrosis in patients who
      had pain on exertion or stiffness in squatting after the reconstructive surgery.

PMID- 9006689
TI  - Analysis of skiing accidents involving combined injuries to the medial collateral
      and anterior cruciate ligaments.
AB  - Two types of ligament injuries common in skiing are the isolated ruptures of the
      anterior cruciate and ruptures of the medial collateral, either with or without
      rupture of the anterior cruciate. Based on research related to ligament injury
      mechanics and two-mode release binding function, the purpose of this paper was to
      critically assess the ability of two-mode release bindings to prevent combined
      medial collateral and anterior cruciate ligament injuries. Making this assessment
      entailed several steps. First, I determined the loads typically transmitted by
      the knee during falls in which combined injuries occurred. Because more than one
      load was transmitted, the next step was to discern which of the loads was more
      damaging. Finally, heel-toe type bindings were evaluated for their potential to
      release in response to damaging loads. I concluded that combined medial
      collateral and anterior cruciate ligament injuries typically occur in forward,
      twisting-type falls in which the primary loads are external axial and valgus
      moments. An external axial moment is more damaging than a valgus moment, both to
      the medial collateral ligament when the joint is intact and to the anterior
      cruciate ligament when the medial collateral ligament is damaged. Because heel
      toe type bindings offer release sensitivity to this moment, the release level of
      the toepiece in twist is an important factor in the prevention of these injuries.

PMID- 9006690
TI  - Preventing anterior knee pain after anterior cruciate ligament reconstruction.
AB  - We studied a group of 602 patients who had anterior cruciate ligament
      reconstructions between 1987 and 1992. An autogenous patellar tendon graft was
      used, regardless of preexisting patellofemoral pain or chondromalacia. The
      surgeon and rehabilitation protocol were the same for all patients, with emphasis
      on obtaining full knee hyperextension postoperatively. All patients were
      evaluated by a questionnaire designed to determine the incidence and severity of
      anterior knee pain as it relates to sporting or daily living activities,
      prolonged sitting, stair climbing, and kneeling. Range of motion for the study
      group was recorded during physical examination. We compared the findings with
      those from a control group of 122 patients who had no previous knee injury. The
      study group reported a mean score of 89.5 +/- 12.5, compared with 90.2 +/- 12.3
      in the control group. Both the operative and control groups reported little or no
      symptoms during sporting activities (94% and 92%, respectively). No differences
      were noted with respect to the other activities surveyed. These results
      demonstrate that anterior knee pain after anterior cruciate ligament
      reconstruction is not an inherent complication associated with patellar tendon
      harvesting. We suggest that the increased incidence of anterior knee pain with an
      autogenous patellar tendon graft can be prevented by obtaining full knee
      hyperextension postoperatively. This goal can be achieved through preoperative
      rehabilitation and a postoperative protocol emphasizing early restoration of full
      knee hyperextension.

PMID- 9006691
TI  - Comparison of two anatomic reconstructions for chronic lateral instability of the
      ankle joint.
AB  - Two anatomic reconstructions for correction of chronic lateral ankle joint
      instability were compared. In a prospective, randomized study, 60 patients were
      allocated to one of two treatment groups: reconstruction of the ligaments as
      described by Karlsson et al. (Group I) or with the modification of the Brostrom
      procedure as described by Gould et al. (Group II). The functional results were
      evaluated with a scoring scale, and the mechanical stability with standardized
      stress radiographs. The minimum follow-up period was 2 years. The functional
      results were satisfactory in 27 of 30 (90%) patients in Group I and 25 of 30
      (83%) in Group II. There was no significant difference between the groups
      regarding mechanical stability. The mean anterior talar translation in Group I
      was 7.1 mm (range, 4 to 10) at followup, compared with 6.7 mm (range, 3 to 9) in
      Group II. The corresponding values for talar tilt were 4.9 degrees (range, 0
      degree to 8 degrees) in Group I and 4.4 degrees (range, 0 degree to 8 degrees) in
      Group II. The duration of operation time was significantly longer in Group II and
      surgical complications were more frequent, probably due to the more extensive
      surgical exposure. This study showed that the majority of patients with chronic
      ankle instability can be successfully treated with anatomic reconstruction of the
      lateral ankle ligaments. Mechanical stability was restored with both methods.

PMID- 9006692
TI  - Ankle inversion injuries. The role of the dynamic defense mechanism.
AB  - We investigated the role of a muscular defense in the stabilization and
      protection of the ankle joint against sudden forced inversion. Ten volunteers
      with mechanically stable ankles were tested in different standing and walking
      situations using a trap door model and lower extremity electromyography and
      electrogoniometers. Peroneal electromyographic activity was observed 54 msec
      after the detection of ankle inversion. This latency was shorter when the ankle
      was already in inversion and longer with the ankle in eversion. Quadriceps and
      hamstring muscle electromyographic activity occurred 68 msec after the ankle
      inversion stimulus. Evidence of active eversion was seen 176 msec after sudden
      inversion. Active changes in knee and hip joint angles occurred even later. In
      contrast, the trap door rotated 30 degrees in approximately 80 msec. We conclude
      that the reflex reaction to sudden inversion is initiated at a peripheral level
      by the inversion motion followed by a reaction pattern mediated by spinal or
      cortical motor centers. Both peripheral and central reactions, however, seem too
      slow to protect the ankle in case of sudden inversion occurring at the time of
      heel contact.

PMID- 9006693
TI  - An eccentric- and concentric-strength profile of shoulder external and internal
      rotator muscles in professional baseball pitchers.
AB  - The purpose of this study was to establish a data base on the isokinetic
      eccentric muscular performance characteristics of external and internal rotator
      muscles in the shoulders of professional baseball pitchers. Concentric data are
      also included and compared with previously published concentric studies. Twenty
      five professional baseball pitchers were evaluated with a Kin-Com isokinetic
      dynamometer. The subjects tested had a mean age of 23.5 years and a mean body
      weight of 199 pounds. Eccentric and concentric isokinetic tests were performed at
      60 and 120 deg/sec. The testing protocol was standardized for each subject. Test
      results indicated no statistically significant difference in mean torque between
      throwing and nonthrowing shoulders for either external or internal rotator muscle
      groups. Eccentric strength was significantly greater than concentric strength for
      all muscle groups tested. The external-to-internal rotator muscle strength ratios
      were well above those previously published for high school through professional
      pitchers. Mean torque-to-lean body weight ratios were also included to establish
      a data base. This study establishes one of the first data bases for eccentric
      isokinetic muscle strength of shoulder rotator muscles in professional baseball
      pitchers. The data may help clinicians prevent and rehabilitate shoulder injuries
      in professional throwing athletes.

PMID- 9006694
TI  - Direct injury to the axillary nerve in athletes playing contact sports.
AB  - We performed long-term followup (31 to 276 months) of 11 contact athletes who had
      sustained isolated injuries to their axillary nerves during athletic competition.
      There were no known shoulder dislocations. Electromyographs were taken of 10
      patients, and all patients had confirmation of clinically defined injuries that
      were confined to their axillary nerves. Nine injuries were sustained while
      tackling opposing players in football; two were sustained in hockey collisions.
      In seven athletes, the mechanism of injury was a direct blow to the anterior
      lateral deltoid muscle. In four athletes, there were simultaneous contralateral
      neck flexion and ipsilateral shoulder depression. At followup, all patients had
      residual deficits of axillary sensory and motor nerve function. There had been no
      deltoid muscle improvement in three patients, moderate improvement in two
      patients, and major improvement in six patients. However, shoulder function
      remained excellent, with all athletes maintaining full range of motion and good
      to-excellent motor strength. Axillary nerve exploration and neurolysis in four
      patients did not significantly affect the outcomes. Although no patient had full
      recovery of axillary nerve function, 10 of 11 athletes returned to their
      preinjury levels of sports activities, including professional athletics.

PMID- 9006695
TI  - Intercondylar notch width and its relation to the configuration and cross
      sectional area of the anterior cruciate ligament. A cadaveric knee study.
AB  - If a narrow intercondylar notch contains a smaller anterior cruciate ligament,
      that may explain why people with narrow notches have a higher incidence of
      anterior cruciate ligament injuries. To investigate the significance of notch
      width measurement, we used 16 embalmed cadaveric knees. A positive mold of the
      entire anterior cruciate ligament, including its femoral and tibial insertions,
      was created with silicone rubber and plaster commonly used for dental molding. We
      had two hypotheses to test from this study. One was that the dimensions of the
      anterior cruciate ligament can be predicted by the notch width. The other was
      that the size of a person's anterior cruciate ligament can be predicted by a
      caliper measurement of the intercondylar notch. The width, sagittal length, and
      cross-sectional area of the midsubstance and the femoral and tibial insertions of
      the anterior cruciate ligament were measured. The notch width index, the ratio of
      notch width to width of the femoral condyle, showed a positive correlation only
      to the ratio of width to sagittal length of the tibial insertion. None of the
      parameters showed any differences between the knees with a notch width index less
      than or equal to 0.2 and those with a notch width index greater than 0.2. The
      knees with small notch width indexes did not have thinner anterior cruciate
      ligaments in them. These findings may not be applicable to knees obtained from
      other races, i.e., not Japanese.

PMID- 9006696
TI  - The pathomechanics of chronic, recurrent cervical nerve root neurapraxia. The
      chronic burner syndrome.
AB  - This study defined chronic recurrent cervical nerve root neurapraxia, the chronic
      burner syndrome, characterized the clinical findings, and described the
      responsible pathomechanics. We studied a subset of 55 athletes (mean age, 22
      years) for evaluation of recurrent burners. Eleven subjects were professional
      athletes. The mechanism of injury was extension combined with ipsilateral-lateral
      deviation in 46 patients (83%). Spurling's sign was positive in 39 patients
      (70%). Twenty-nine patients (53%) had developmentally narrowed cervical canals,
      and 48 patients (87%) had evidence of disk disease by magnetic resonance imaging.
      The disk disease was in the form of a disk bulge, disk protrusion, or a frank
      disk herniation deforming the cord. Fifty-one patients (93%) had disk disease or
      narrowing of the intervertebral foramina secondary to degenerative disk disease.
      Although burners may be the result of a brachial plexus stretch injury in high
      school and collegiate football players seen with acute symptoms, nerve root
      compression in the intervertebral foramina secondary to disk disease is a more
      common cause in collegiate and professional players who have recurrent or chronic
      burner syndromes. There is a high incidence of cervical canal stenosis in
      football players with recurrent burner syndrome. The combination of disk disease
      and cervical spinal canal stenosis may lead to an alteration in normal cervical
      spine mechanics that may make these athletes more prone to chronic burner
      syndromes.

PMID- 9006697
TI  - Acute posterolateral rotatory subluxation of the elbow joint. A case report.
AB  - The elbow joint has become increasingly recognized as a very important joint for
      all sports activities. Players in some sports cannot compete at all with an
      unstable elbow due to ligament injuries. Thus, professional sports players and
      heavy laborers, as in our case, should find the excellent results of primary
      ligament repair preferable. This technique is less invasive than secondary
      ligament reconstruction and can result primarily in an accurate, stable elbow
      with full range of motion for mobilizing the joint and muscles at an early stage.

PMID- 9006698
TI  - Preseason hamstring muscle weakness associated with hamstring muscle injury in
      Australian footballers.
AB  - Hamstring muscle strain is the most prevalent injury in Australian Rules
      Football, accounting for 16% of playing time missed as a result of injury. Thirty
      seven professional footballers from an Australian Football League team had
      preseason measurements of hamstring and quadriceps muscle concentric peak torque
      at 60, 180, and 300 deg/sec measured on a Cybex 340 dynamometer. Players were
      studied prospectively throughout the 1995 season. During that time, six players
      sustained clinically diagnosed hamstring muscle injuries that caused them to miss
      match-playing time. The injured hamstring muscles were all weaker than in the
      opposite leg in absolute values and hamstring-to-quadriceps muscle ratios.
      According to our t-test results, hamstring muscle injury was significantly
      associated with a low hamstring-to-quadriceps muscle peak torque ratio at 60
      deg/sec on the injured side and a low hamstring muscle side-to-side peak torque
      ratio at 60 deg/sec. Flexibility (as measured by the sit-and-reach test) did not
      correlate with injury. Discriminant-function analysis using the two significant
      ratio variables resulted in a canonical correlation with injury of 0.4594 and
      correctly classified legs into injury groups with 77.4% success. These results
      indicate that preseason isokinetic testing of professional Australian Rules
      footballers can identify players at risk of developing hamstring muscle strains.

PMID- 9006699
TI  - Surgical management of refractory trochanteric bursitis.
AB  - We reviewed a single surgeon's experience with the surgical management of
      refractory trochanteric bursitis in an active population group. The surgical
      procedure consisted of simple longitudinal release of the iliotibial band over
      the greater trochanter and excision of the subgluteal bursa. To our knowledge,
      this is the first series to use this technique. Seven hips in five patients form
      the basis of the study, making it one of the largest surgical series reported.
      All patients had no improvement after a minimum of 1 year of nonoperative
      management consisting of nonsteroidal antiinflammatory medication, iliotibial
      band stretching, diathermy, ultrasound, and injections of local anesthetics
      combined with corticosteroids (average, 4.8 injections). Patients had experienced
      symptoms preoperatively for an average of 3.8 years and had noted marked
      limitation in vocational and recreational activities. The preoperative Harris hip
      score averaged 51.7. Four of the five patients (six hips) were available for
      evaluation at the time of this study, at an average of 20 months postoperatively.
      The average Harris hip score was 95.0. All patients were satisfied with the
      surgical results and had returned to unrestricted vocational and athletic
      activities. The remaining patient was last seen 6 months postoperatively and her
      Harris hip score had improved from 49 to 84.

PMID- 9006700
TI  - End-to-end operative repair of Achilles tendon rupture.
AB  - We present the long-term results of operative repair in 23 consecutive patients
      with Achilles tendon ruptures, treated between 1984 and 1991, to evaluate our
      treatment method and determine the clinical causes of rupture. Fifty-four percent
      of ruptures occurred in people in their 30s; 90% occurred during participation in
      acceleration-deceleration sports. All but three patients were treated within 1
      week of injury with open, operative, end-to-end repair of the Achilles tendon.
      The remaining three patients were treated more than 3 weeks after injury. All
      patients followed a standard postoperative regimen. Followup averaged 3.6 years
      (range, 1 to 7.5). Seventeen patients were available for Cybex analysis, and the
      remaining patients were interviewed personally or by telephone. Subjectively,
      patients were very satisfied with the results of treatment. Objectively, physical
      examination and Cybex testing to measure strength and endurance revealed results
      somewhat better than those previously reported with operative repair. No patient
      experienced a rerupture, although one attenuated repair was noted 9 months
      postoperatively. Only two minor wound problems were recorded. Long-term results
      revealed near-normal function when comparing the injured side with the uninjured
      side. Ninety-two percent of patients returned fully to their preinjury levels of
      activity.

PMID- 9006701
TI  - Effects of finger and wrist taping on grip strength.
AB  - Taping of the fingers and wrists by professional and collegiate football players
      has become increasingly prevalent because many players believe taping provides
      them with increased grip strength. This study was conducted to determine whether
      taping of the fingers or wrists or both enhances grip strengths in football
      players. Twenty-five players who self-tape in game situations volunteered for the
      study. Grip strengths in both taped and untaped conditions (trials) were measured
      with a hand-held grip dynamometer. Each athlete completed five measurement
      trials. No statistically significant difference was found between the untaped
      dominant hand and the dominant hand with the fingers-only taped. There was no
      significant difference between the untaped nondominant hand and the nondominant
      hand with the wrist-only taped. The untaped dominant hand was significantly
      stronger than the taped dominant hand, with mean grip strengths of 142.7 versus
      137.8 pounds. The results of these clinical measurements of grip strength showed
      that, contrary to the perceptions of professional and major college football
      players, taping of the fingers or wrists or both the fingers and wrists does not
      improve grip strength.

PMID- 9006702
TI  - Effects of initial graft tension on clinical outcome after anterior cruciate
      ligament reconstruction. Autogenous doubled hamstring tendons connected in series
      with polyester tapes.
AB  - We conducted a prospective, randomized, short-term study to clarify the effects
      of initial graft tension on clinical outcome after arthroscopically assisted
      anterior cruciate ligament reconstruction with autogenous doubled semitendinosus
      and gracilis tendons connected in series with polyester tapes. Seventy Japanese
      patients with chronic, "isolated" anterior cruciate ligament tears were entered
      in the study. The patients were randomly divided into three groups based on
      initial graft tension: Group 1 (20 N), Group 2 (40 N), or Group 3 (80 N). No
      statistical differences were noted among the three groups with regard to their
      background factors. The patients were observed for 2 years or more after surgery.
      Postoperatively, the average side-to-side difference in anterior laxity was 2.2
      +/- 2.4 mm in Group 1, 1.4 +/- 1.8 mm in Group 2, and 0.6 +/- 1.7 mm in Group 3.
      Analysis of variance testing showed that the postoperative laxity in Group 3 was
      significantly less than that in Group 1. Spearman's rank-order correlation
      analysis also demonstrated significant correlation between the magnitude of
      initial graft tension and the magnitude of the postoperative laxity. This study
      demonstrates that relatively high initial tension (up to 80 N) reduces the
      postoperative anterior laxity of the knee joint after anterior cruciate ligament
      reconstruction using the doubled autogenous hamstring tendons connected in series
      with polyester tapes.

PMID- 9006704
TI  - Elongation of arthroscopically tied knots.
AB  - It has been postulated that some arthroscopic shoulder stabilization failures may
      be due to knot slippage. In an effort to improve arthroscopic technique, we
      performed tensile testing on four arthroscopically tied knots with two commonly
      used suture materials. Handtied square knots served as controls. Sutures of No. 1
      Maxon and No. 1 Ticron were used. Four types of sliding knot configurations were
      tested: the overhand loop, the Duncan loop, the Roeder knot, and the Snyder knot.
      Knots were tied via a knot pusher, and testing was performed in a normal saline
      filled thermoplastic chamber. Knots were tied around two rings connected to a
      Bionix 858 materials testing apparatus. The knots were tested under conditions of
      cyclic loading and loading to failure. Results of the testing revealed that the
      most important factor in knot security was the type of suture material, although
      there were differences with the type of knot. With the Maxon suture, there was
      significantly decreased ultimate failure load of all of the arthroscopically tied
      knots compared with handtied square knots. Knots tied with Ticron were similar in
      strength for both arthroscopically and handtied groups. The surgeon who chooses a
      monofilament absorbable suture should be aware that a high percentage of knots
      fail under low load cyclic testing, and that all of these knots were inferior to
      handtied square knot controls in testing to failure.

PMID- 9006705
TI  - The role of the knee brace in the prevention of anterior knee pain syndrome.
AB  - Our prospective study evaluates the use of a knee brace with a silicon patellar
      support ring as a method of preventing anterior knee pain from developing in
      young persons undergoing strenuous physical exercise. We studied 60 young
      athletes, who qualified for a strenuous physical training course and who had not
      suffered from anterior knee pain previously. Twenty-seven subjects were in the
      brace group and 33 were in the nonbrace control group. The incidence of anterior
      knee pain syndrome increased with the intensity of exertion as the study
      progressed; i.e., subjects ran 6 km in the 1st week, gradually increasing each
      week up to 42 km/week at the 8th week. Yet, there was a significant reduction in
      the incidence of the syndrome at the end of the study in male athletes who had
      applied the braces before exercise sessions and in the brace group as a whole,
      compared with the control group. Prophylactic use of the brace, as described, did
      not reduce the ability of the athletes who wore braces to improve their physical
      fitness parameters in response to exercise. These data indicate that the use of a
      brace may be an effective way to prevent the development of anterior knee pain
      syndromes in persons participating in strenuous and intensive physical exercise.

PMID- 9006703
TI  - The effect of thermal heating on the length and histologic properties of the
      glenohumeral joint capsule.
AB  - The purpose of this study was to evaluate the effect of temperature on shrinkage
      and the histologic properties of glenohumeral joint capsular tissue. Six fresh
      frozen cadaveric shoulders were used for this study. Seven joint capsule
      specimens were taken from different regions from each glenohumeral joint and
      assigned to one of seven treatment groups (37 degrees, 55 degrees, 60 degrees, 65
      degrees, 70 degrees, 75 degrees, 80 degrees C) using a randomized block design.
      Specimens were placed in a tissue bath heated to one of the designated
      temperatures for 10 minutes. Specimens treated with temperatures at or above 65
      degrees C experienced significant shrinkage compared with those treated with a 37
      degrees C bath. The posttreatment lengths in the 70 degrees, 75 degrees, and 80
      degrees C groups were significantly less than the pretreatment lengths.
      Histologic analysis revealed significant thermal alteration characterized by
      hyalinization of collagen in the 65 degrees, 70 degrees, 75 degrees, and 80
      degrees C groups. This study demonstrated that temperatures at or above 65
      degrees C caused significant shrinkage of glenohumeral joint capsular tissue.
      These results are consistent with histologic findings, which revealed significant
      thermal changes of collagen in the 65 degrees, 70 degrees, 75 degrees, and 80
      degrees C groups. To verify the validity of laser application for shrinkage of
      joint capsule, studies designed to compare these findings with the effects of
      laser energy must be performed.

PMID- 9006706
TI  - Compartment syndrome after arthroscopic surgery of knee. A report of two cases
      managed nonoperatively.

PMID- 9006707
TI  - Bilateral, exercise-induced thigh compartment syndrome diagnosed as exertional
      rhabdomyolysis. A case report and review of the literature.

PMID- 9006709
TI  - A statistics primer. Power analysis and sample size determination.

PMID- 9006708
TI  - The role of proprioception in the management and rehabilitation of athletic
      injuries.
AB  - Rehabilitation continues to evolve with the increased emphasis on patient
      management and proprioceptive training. Proprioception can be defined as a
      specialized variation of the sensory modality of touch that encompasses the
      sensation of joint movement (kinesthesia) and joint position (joint position
      sense). Numerous investigators have observed that afferent feedback to the brain
      and spinal pathways is mediated by skin, articular, and muscle mechanoreceptors.
      Examining the effects of ligamentous injury, surgical intervention, and
      proprioceptively mediated activities in the rehabilitation program provides an
      understanding of the complexity of this system responsible for motor control. It
      appears that this neuromuscular feedback mechanism becomes interrupted with
      injury and abnormalities, and approaches restoration after surgical intervention
      and rehabilitation. Rehabilitation programs should be designed to include a
      proprioceptive component that addresses the following three levels of motor
      control: spinal reflexes, cognitive programming, and brainstem activity. Such a
      program is highly recommended to promote dynamic joint and functional stability.
      Thus far, current knowledge regarding the basic science and clinical application
      of proprioception has led the profession of sports medicine one step closer to
      its ultimate goal of restoring function.

PMID- 9006711
TI  - Spatial distribution of postotic crest cells defines the head/trunk interface of
      the vertebrate body: embryological interpretation of peripheral nerve morphology
      and evolution of the vertebrate head.
AB  - The migration pathways and spatial distribution of neural crest cells largely
      depend on the embryonic architecture. At the preotic level in the chick embryo,
      cephalic crest adhere to even-numbered rhombomeres proximally, and populate each
      pharyngeal arch distally, thus prefiguring the morphology of the branchiomeric
      nerves. This distribution pattern is possible because of the absence of somites
      in the head. In the postotic region, however, somites and pharyngeal arches
      coexist at the same axial level. The caudalmost cephalic crest cell population,
      the circumpharyngeal crest cells, are derived from the postotic crest and their
      distribution covers the entire innervation areas of cranial nerves IX and X. In
      their proximal migration pathway, circumpharyngeal crest cells can exist along
      the dorsolateral pathway only where somites are absent. They divert around the
      occipital somites rostrally, making an arc that represents the caudal limit of
      the dorsolateral pathway of cephalic crest cells, or the head/trunk interface at
      the paraxial level. Ventrally, the circumpharyngeal crest cells localize in
      postotic pharyngeal arches as well as in an arc-shaped ridge, called the
      circumpharyngeal ridge. Since the circumpharyngeal ridge represents the caudal
      limit of the pharynx, it indicates the head/trunk interface at the level of the
      lateral body wall. These two interfaces of reverse orientation make an S-shaped,
      head/trunk interface together. Several structures unique to this region develop
      in this interface. Since the rhombomeric compartmentalization is distinct only in
      higher vertebrates, the rhombomere-dependent segregation of cephalic crest cells
      is more likely to be a secondary feature of the vertebrate head. The
      topographical configuration of the vertebrate crest cell distribution pattern
      does not support the idea that the vertebrate head evolved as a specialized
      trunk. but rather supports the idea that two distinct methods of segmental
      patterning have evolved in rostral and caudal parts of the vertebrate body, which
      resulted in the head and trunk, respectively. Postotic crest is located at the
      intermediate level between the trunk and the head, giving rise to both the
      cephalic and trunk crest cells. Its cephalic components circumpharyngeal crest
      cells, are distributed only rostral to the S-shaped interface.

PMID- 9006710
TI  - Diagnosis of glenoid labral tears: a comparison between magnetic resonance
      imaging and clinical examinations.

PMID- 9006712
TI  - Axogenesis in the human fetal auditory system, demonstrated by neurofilament
      immunohistochemistry.
AB  - Morphological, electrophysiological and behavioral evidence indicates that the
      onset of rapid, synchronized conduction of auditory impulses occurs in the human
      brainstem during the 28th-29th fetal weeks. This implies that axonal connections
      in the brainstem auditory pathway are generated prior to this time. In order to
      investigate the sequence of axogenic events in the human brainstem pathway, we
      employed immunohistochemical techniques and an antibody to neurofilament protein.
      Immunostaining for axonal neurofilaments in an age-graded series of fetal brains
      demonstrates that a small number of cochlear nerve axons have invaded the ventral
      cochlear nucleus by the 16th fetal week. By this same time point, a limited
      number of trapezoid body-lateral lemniscus axons have reached the superior
      olivary complex and inferior colliculus. Between gestational weeks 16 and 26,
      there is marked expansion and collateralization of the ascending pathway from
      cochlear nerve to inferior colliculus. By week 26, ascending axons have begun to
      form plexuses of terminal neuropil within all of the brainstem auditory nuclei.
      Beginning in week 22, there is development of commissural axons (dorsal
      commissure of the lateral lemniscus and commissure of the inferior colliculus)
      and descending projections (descending collicular axons and olivocochlear
      bundle). This early establishment of a mature pattern of axonal connections
      presumably forms the basis for the appearance of myelin, acousticomotor reflexes
      and recordable brainstem responses by fetal week 29.

PMID- 9006713
TI  - Expression and localization of annexin V and annexin VI during limb bud formation
      in the rat fetus.
AB  - We have investigated the expression and the localization of annexin V and annexin
      VI during the development of rat fetal limb buds by immunoblot and
      immunocytochemical analysis. Neither annexin V nor annexin VI was detectable in
      undifferentiated mesenchymal cells in limb buds of the day-13-day-16 rat fetus.
      Skeletal muscles, whose progenitor cells migrate from the somites and appeared in
      the limb buds at day 14, dramatically expressed annexin VI on the cell surface
      after differentiation from mononucleated myogenic cells into multinucleated
      myotubes. At day 16 both annexin V and annexin VI were found to be expressed in
      differentiated chondrocytes as well as in the perichondrium, a precursor of
      chondrocytes, whereas the compact layer of mesenchymal cells surrounding a
      chondrification center (precartilage) did not show any immunoreactivity for
      either of these proteins. The results suggest a close relationship between the
      expression of these annexins and cell differentiation of chondrocytes and
      skeletal muscles during limb but development.

PMID- 9006714
TI  - Jejunal and ileal Peyer's patches in pigs differ in their postnatal development.
AB  - The postnatal development of the jejunal and ileal Peyer's patches was studied
      before and after weaning in 1-, 1.5- and 2-month-old pigs. The follicles of the
      jejunal Peyer's patches grew with age and were two times longer and wider in
      specified pathogen-free and conventional pigs than in germ-free animals, thus
      indicating an influence of the living microbial antigens from the gut lumen. In
      germ-free pigs the size of the ileal Peyer's patch follicles increased between
      the 1st and 2nd month, whereas in the specified pathogen-free and conventional
      animals these follicles were comparable in size in all three age groups. In 1- to
      1.5-month-old pigs the interfollicular area of jejunal Peyer's patches was wider
      (0.1 +/- 0.04 mm) than that of the ileal Peyer's patch (0.04 +/- 0.03 mm).
      Immunohistological studies showed that in germ-free pigs preferentially surface
      IgM+ but few IgA+ B cells were present in the follicles, domes and dome
      epithelia. In specified pathogen-free and conventional pigs the B cells expressed
      different levels of surface or cytoplasmic IgM or IgA. In all groups studied,
      more T cells were observed in the jejunal than in the ileal Peyer's patch. Here,
      few T lymphocytes were found because of the small interfollicular areas. Small
      numbers of Null cells were distributed in the interfollicular regions of all
      animals. The results show that living microbial antigens have a major influence
      on the jejunal and ileal Peyer's patches in pigs. The morphological differences
      between the two types of Peyer's patches are an indication that they develop
      differently during postnatal life. So far it remains unclear whether these
      morphological differences reflect a specific function of the pig's ileal Peyer's
      patch, such as the expansion of the genetically determined B cell repertoire as
      has been reported for sheep.

PMID- 9006715
TI  - Early expression of recoverin in a unique population of neurons in the human
      retina.
AB  - The calcium-binding protein recoverin has been reported as present in
      photoreceptors, cone bipolar cells and sparse cells in the ganglion cell layer in
      the adult retinae of various vertebrate species. The present study was undertaken
      to clarify the developmental pattern of recoverin-immunoreactive cells in the
      human retina with particular attention to the cells in the inner retinal layers.
      In the adult human retina, small populations of recoverin-containing cells are
      present in the ganglion cell and nerve fiber layers. However, the precursors of
      these cells are quite numerous on the inner and outer borders of the nerve fiber
      layer in the fetal retina. By 13 weeks of gestation these cells express recoverin
      very intensely. By 24 weeks they are mature-looking with relatively large soma
      sizes (mean = 118 microns 2) and appear round, oval or multipolar in shape, with
      varying numbers of short processes. There follows a noticeable reduction of the
      mean soma size, but little change in morphology and process number during the
      remaining gestational stages up to and after birth. The mean numerical density of
      the recoverin-positive cells in the fetal inner retinal layers is gradually
      reduced from the high level at 13 weeks until birth, when there is a great drop
      to the adult level. The recoverin-immunoreactive cells in the ganglion cell layer
      demonstrate distinctively different developmental and morphological features from
      the principle neurons and glial cells in the retina. They are probably the
      neurons derived from the marginal zone of the retinal primordium that reside in
      the inner and outer borders of the nerve fiber layer due to the invasion of
      ganglion cell axons. The expression of recoverin in the neurons may be
      significant in maintaining an inside-out and centroperipheral gradient of calcium
      concentration in the premature retina, thereby playing a role in determining the
      polarity of the differentiating ganglion cells and the growth of their axons in a
      centrifugal spatiotemporal order.

PMID- 9006716
TI  - Developmental changes of glutamate receptors in the rat cerebral cortex and
      hippocampus.
AB  - We studied the immunohistochemical localization of the glutamate receptors (GluR
      1, -2, and -3,) in the developing rat cerebral cortex and hippocampus using
      antibodies to GluR1 and to an epitope common to GluR2 and GluR3 (GluR2/3)
      subunits. In the cerebral cortex, GluR1 immunoreactivity appeared in the neurons
      from postnatal day (PND) 0, increased with maturation, was highest at PND 10,
      decreased until PND 30, and thereafter remained at the same level as on PND 0.
      GluR2/3 immunoreactivity appeared earlier in scattered neurons on embryonal day
      (ED) 18, increased with maturation and reached a peak between PND 10 and PND 15,
      after which the immunoreactivity gradually decreased and reached a plateau at PND
      30. For both GluR1 and GluR2/3, some of the pyramidal neurons showed intense
      staining. In the pyramidal layers of the hippocampus, GluR1 and GluR2/3
      immunoreactivity was found in all the pyramidal neurons of the CA1-4 area from ED
      20. In the dentate gyrus of the hippocampus, GluR1 and GluR2/3 immunoreactivity
      was found in the neurons of the granule cells after PND 0. Immunoreactivity in
      the neurons of the subiculum was found after PND 5 and that of the polymorphic
      cell layers was found after PND 15-20. Our results indicate that the development
      of glutamate receptor subunits in the rat cerebral cortex and hippocampus is
      expressed in different spatial patterns and distinct temporal patterns throughout
      development and is scheduled during the early postnatal period, when synaptic
      plasticity or synaptic connection occurs in these regions.

PMID- 9006717
TI  - Regulation of gene expression in cultured embryonic mouse mandibular mesenchyme
      by serotonin antagonists.
AB  - During murine embryogenesis, uptake sites for the neurotransmitter serotonin (5
      HT) are transiently expressed in craniofacial epithelial structures. Based on
      malformations produced in cultured mouse embryos exposed to uptake inhibitors or
      receptor ligands, we have proposed that 5-HT acts as a dose-dependent
      morphogenetic signal during critical periods of craniofacial development. Several
      5-HT receptor subtypes are co-distributed with tenascin and the calcium binding
      protein S-100 beta in developing craniofacial mesenchyme. Since these molecules
      are thought to be important for craniofacial development, their regulation by 5
      HT could mediate some of its morphogenetic actions. Mandibular mesenchyme cells,
      from E12 mouse embryos (plug day = E1), grown in micromass cultures were used as
      an in vitro model to investigate whether 5-HT regulates expression of these
      molecules. Immunocytochemistry revealed expression of S-100 beta, tenascin,
      cartilage proteoglycan core protein (a component of the cartilage matrix) and a
      variety of 5-HT receptors in these cultures. To block the actions of 5-HT (from
      serum in the culture medium), cultures were exposed to one of these selective 5
      HT receptor antagonists and effects on expression were investigated using
      quantitative immunobinding and in situ hybridization assays. These antagonists
      differentially regulated expression of cartilage core protein, S-100 beta and
      tenascin. Antagonism of 5-HT3 receptors by Zofran or 5-HT1A receptors by NAN-190
      reduced the amount of core protein, whereas antagonism of 5-HT2A-C receptors by
      mianserin had no significant effect. All three antagonists stimulated levels of
      tenascin mRNA and protein. Expression of S-100 beta mRNA and protein was
      inhibited by Zofran and stimulated by mianserin, whereas NAN-190 had no
      significant effect. The differential effects of antagonists suggest that in vivo,
      5-HT could: (1) promote expression of cartilage core protein by activation of 5
      HT3 or 5-HT1A receptors, (2) inhibit production of tenascin by activation of
      multiple receptors, (3) promote or inhibit synthesis of S-100 beta by activation
      of 5-HT3 or 5-HT2 receptors, respectively. These actions may be important
      components of the morphogenetic functions of 5-HT during craniofacial
      development.

PMID- 9006718
TI  - Phenotype of cultured fetal perivascular cells from human placenta studied by
      scanning electron microscopy.
AB  - The phenotype of perivascular placental cells has previously been studied using
      tissue sections from the fetal villi. The examination of these cells in culture
      by scanning electron microscopy gives us the opportunity to observe their three
      dimensional phenotypes and associations outside their normal constraints. Human
      umbilical endothelial cells, which have a phenotype comparable to that observed
      in other studies, seem more flattened in culture than in their usual environment.
      Microvascular endothelial cells did not attain an epithelioid phenotype with
      close contacts between cells but formed a network of branched, elongated cells
      with phagocytotic activity. Some circular associations were observed when using a
      gelatinized matrix. Microvascular pericytes were large, flattened cells with an
      irregular border that pushed up nodular associations on a gelatin matrix.
      Chorioplacental myocytes adopted a network template comparable to that developed
      by microvascular endothelial cells. However, these elongated cells were thicker,
      without microvilli, and superficial filaments could be observed. In culture,
      confluent endothelial cells from the umbilical cord or microvascular pericytes
      associated as nodules reached a cell phenotype close to their in vivo counter
      parts. This attainment of an in vivo phenotype remains questionable for
      chorioplacental myocytes. Microvascular endothelial cells, however, though there
      was sparse formation of circular associations, remained far from their in vivo
      phenotype.

PMID- 9006719
TI  - An immunohistochemical analysis of the ontogeny, distribution and coexistence of
      12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the
      digestive tract of the turbot, Scophthalmus maximus (Teleostei).
AB  - The ontogeny of endocrine cells and nerve fibers containing immunoreactivities
      for 12 regulatory peptides and serotonin was studied in the digestive tract of a
      flatfish, the turbot (Scophthalmus maximus), using antisera specific for
      mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR)
      endocrine cells were detected from day 5 to day 10 in stomach and intestine I.
      Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine
      I. In contrast to the islet cells, they reacted with antisera against mammalian
      (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti
      mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present
      in the gastro-entero-pancreatic system and the enteric nervous system.
      Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP
      immunoreactivities coexisted throughout development. In entero-endocrine cells,
      NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric
      nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No
      coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first
      insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They
      seemed to contain none of the other peptides. Their number and distribution
      exhibited great interindividual differences. Vasoactive intestinal polypeptide
      (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP
      IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)
      IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day
      17. The first serotonin (SER)-IR cells were observed in the stomach anlage around
      day 10 and SER-IR nerve fibers at day 15 throughout the gastro-intestinal tract.
      Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach
      and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected
      around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells
      were identified in the stomach anlage and intestine I around day 8 and contained
      NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several
      developmental phases can be distinguished: (1) at the onset of exogenous feeding
      only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a
      differentiated entero-endocrine system establishes during the early phase of
      exogenous feeding; (3) before the final differentiation of stomach and gut
      GAS/CCK-IR cell appear; (4) after metamorphosis most of the different types of
      regulatory peptide-containing nerve fibers develop, probably setting up the fine
      regulation of gastro-intestinal blood flow and motility.

PMID- 9006721
TI  - Comparison of cationic myocardial perfusion agents: characteristics of
      accumulation in cultured smooth muscle cells.
AB  - The uptake and washout kinetics of two cationic lipophilic 99mTc-labeled
      myocardial perfusion agents, 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) 99mTc
      1,2-bis[bis-2-ethoxyethyl)-phosphino]ethane (99mTc-Tetrofosmin), were studied in
      cultured smooth muscle cells and compared to the conventional myocardial
      perfusion agent, 201Tl. Both 99mTc-MIBI and 99mTc-Tetrofosmin had a 4-fold
      greater uptake then 201Tl, and they were washed out of cells through similar
      kinetics which had slower rates than 201Tl. Incubation with metabolism inhibitors
      had a modest influence on the uptake of these two 99mTc-labeled agents, although
      their extent and inhibited sites were slightly different. Ion transport
      inhibitors did not affect the uptake of 99mTc-MIBI, although the 99mTc
      Tetrofosmin uptake was slightly inhibited when the Ca2+ channel was blocked. Our
      studies indicate that 99mTc-MIBI and 99mTc-Tetrofosmin were taken up by smooth
      muscle cells in similar pharmacokinetic patterns, but their accumulation
      reflected a different meaning for cell viability.

PMID- 9006720
TI  - Nuclear medicine applications in immunosuppressed patients, "AIDS".

PMID- 9006723
TI  - Usefulness of Ga-67 brain SPECT in patients with CNS malignant lymphoma.
AB  - The efficacy of Ga-67 SPECT imaging of CNS malignant lymphoma was investigated in
      14 studies of 11 patients. As compared with planar images, the SPECT imaging
      improved the detectability of the focus of CNS malignant lymphoma. All untreated
      cases showed L/N ratios higher than 3.0. And the L/N ratios also changed
      according to remission or relapse of CNS malignant lymphoma.

PMID- 9006722
TI  - Clinical application of three-dimensional myocardial imaging: evaluation of
      efficacy of medical treatment on myocardial perfusion.
AB  - To investigate the clinical applicability of the three-dimensional (3D)
      myocardial imaging using a newly developed system (the Application Visualization
      System-Medical Viewer), thallium-201 myocardial single photon emission computed
      tomography was performed in 19 patients with previous myocardial infarction
      before and after treatment with nisoldipine. We have developed a new method for
      automatically reconstructing 3D imaging for the stereoscopic evaluation of
      myocardial perfusion. The left ventricular myocardial volume with a radioisotope
      count > or = 50% of maximum was calculated by using the conventional surface
      rendering method. With these images, the effect of nisoldipine on myocardial
      perfusion was assessed and the myocardial volume with a radioisotope count > or =
      50% of maximum was compared. In fifteen (88%) of 19 patients, myocardial
      perfusion increased in the infarct areas after nisoldipine treatment. Nisoldipine
      significantly increased the myocardial volume with a radioisotope count > or =
      50% of maximum from 141 +/- 17 to 153 +/- 18 ml on the stress 3D imagings. These
      findings indicate that nisoldipine improved myocardial perfusion during exercise.
      3D imaging provided stereoscopic assessment of the changes in myocardial
      perfusion following treatment with nisoldipine and also detected transient
      enlargement of the left ventricular lumen induced by exercise.

PMID- 9006724
TI  - Uptake of radioactive octanoate in astrocytoma cells: basic studies for
      application of [11C]octanoate as a PET tracer.
AB  - Fatty acids are taken up and metabolized in the brain. In vitro uptake
      experiments on astrocytoma cells were carried out to assess the potential use of
      [1-11C]octanoate as a positron emission tomography (PET) tracer for astroglial
      functions. Uptake of [1-14C]octanoate increased in a time-dependent fashion until
      60 min after application. The uptake of [1-11C]octanoate showed similar results
      to that of [1-14C]octanoate until 10 min. As for medium pH, [1-14C]octanoate
      uptake increased gradually with the decrease in pH. We also examined the effects
      of glutamate, glucose deprivation and hypoxia on the uptake of octanoate and
      found that these conditions did not bring about any change in the extent of [1
      14C]octanoate uptake. These results show that the octanoate uptake was not
      influenced by any of several pathological conditions. When the number of
      astrocytes increases in the area of hypoglycemia or hypoxia near a brain lesion,
      the amount of octanoate uptake also increases, so this indicates the possibility
      that 11C-octanoate will detect a brain lesion.

PMID- 9006725
TI  - Quantitative renography with the organ volume method and interporative background
      subtraction technique.
AB  - When quantification of renal activity is performed by planar imaging, many
      correction factors must be considered. To obtain quantitative renal images and
      renogram, we have examined our proposed method by using the organ volume for
      scatter, attenuation, and background activity, and the interporative background
      subtraction (IBS) technique in phantom and clinical studies. A renal phantom
      study was performed by varying the renal depth from 3 to 11 cm and the kidney-to
      background activity concentration ratio from 5 to 80. Planar images were properly
      corrected for scatter, attenuation and background activity by our method and the
      corrected images were compared with the images obtained by the conventional
      method for the estimation of true renal activity. Clinical Tc-99m DTPA dynamic
      data for both a good and a poor renal function were also corrected by our method
      and volume-corrected renograms were obtained. For the phantom study, depth
      independent images were obtained and these images gave a good estimation of the
      true count rate. In the clinical study, the conventional renogram was especially
      modified to allow for oversubtraction of background counts in the early phase (0
      4 min). In conclusion, our proposed correction method can assess renal function
      qualitatively and quantitatively in both static and dynamic planar renal imaging.

PMID- 9006726
TI  - Abdominal SPECT/MRI fusion applied to the study of splenic and hepatic uptake of
      radiolabeled thrombocytes and colloids.
AB  - The importance of applying MRI (CT)/SPECT fusion in the abdominal and thoracic
      areas has been recognized in recent studies aiming at radionuclide therapy of
      cancer. According to our earlier results spleen and liver volume determination
      with different segmentation methods is inaccurate with SPECT alone. We therefore
      applied a SPECT/MRI registration procedure to the estimation of spleen and liver
      volumes and spleen/liver activity ratios in three male volunteers administered
      111In-labeled thrombocytes and 99mTc-labeled colloids. The objectives of the
      study were to investigate if the uptake of thrombocytes in the spleen and liver
      can be measured more accurately when the anatomical borders of these organs are
      transferred from MRI to SPECT, and to test a SPECT/MRI registration method for
      improving three-dimensional dosimetry for radiotherapy treatment planning. A good
      correlation was found between spleen/liver activity ratios calculated from
      volumetric average activity per pixel values and from total volumetric counts
      derived from registered data but not from projection data. The average
      registration residual with this SPECT/MRI fusion method is approximately 1-2 cm
      in the abdominal area. Combining anatomical images with SPECT is therefore
      important for improving quantitative SPECT also in the abdomen.

PMID- 9006729
TI  - Accumulation of Tc-99m MIBI in breast lymphoma: comparison with Ga-67 citrate.
AB  - We report 2 cases of malignant lymphoma of the breast which were clearly shown on
      total body imaging as well as on SPECT with Ga-67 and Tc-99m MIBI. Tumor
      accumulation of Ga-67 was seen in all cases including a recurrent tumor. Ga-67
      scintigraphy is useful for follow up in detecting relapse, as well as in
      predicting responses to therapy. Tc-99m MIBI was found to accumulate in the
      malignant lymphoma of the breast, and especially SPECT images of breast lesions
      provided better contrast than planar images, and Tc-99m MIBI SPECT could diagnose
      localization of the tumor because there was no uptake by the breast. But the Tc
      99m MIBI accumulation of the tumor was lower than Ga-67.

PMID- 9006728
TI  - Ring appearance of Tc-99m MIBI thoracic SPECTs and increased uptake on Tc-99m
      HMDP thoracic SPECTs in a pulmonary mass of small cell carcinoma.
AB  - Tc-99m MIBI is taken up avidly by viable tumor tissue and does not accumulate in
      the necrotic carcinoma. We present a patient who underwent Tc-99m MIBI and Tc-99m
      HMDP thoracic SPECTs: a large area of increased MIBI uptake with central
      photopenia (ring appearance) in the right upper lung localizes bone imaging agent
      and does not localize multiple areas of intense uptake in the metastatic hilar
      mediastinum lymph nodes. Rapid growth of tumor cells in the lung leading to
      central necrosis/ischemia accounts for bone imaging agent localization in the
      tumor, as well as the ring-appearance of lung mass on Tc-99m MIBI imaging. These
      findings may reflect less viability of the lung tumor as compared with intense
      MIBI uptake in hilar/mediastinal lymph node uptake without bone agent
      localization.

PMID- 9006727
TI  - Evaluation of Tc-99m(V) DMSA for imaging inflammatory lesions: an experimental
      study.
AB  - The present study evaluated 99mTc(V) DMSA as an agent for the visualization of
      inflammatory lesions in comparison to 99mTc(III) DMSA and 99mTC-HIG. All three
      radiopharmaceuticals were prepared with commercial kits. 99mTc(V) DMSA was
      prepared at neutral pH by the addition of first bicarbonate and then
      pertechnetate to the kit contents. The labeling efficiency was 99% as determined
      by ITLC. Abscesses were induced by i.m. injection of 50 microliters turpentine
      into the right thighs of 36 Swiss albino mice. Six days later 3.7 MBq of each
      radiopharmaceutical was i.v. administered to 12 mice. The mice were sacrificed at
      1, 3, 6 and 24 h later. Scintigrams were obtained with a gamma camera. The
      abscesses were better visualized on scintigrams with 99mTc(V) DMSA compared to
      99mTc(III) DMSA, starting at 1 h. The animals were dissected and the organs were
      removed, weighed and the radioactivity determined with a gamma counter. The
      abscess to other tissue ratios were higher with 99mTc(V) DMSA than the other
      radiopharmaceuticals. The max. abscess/muscle ratios were 9.46 +/- 3.20 (24 h),
      4.19 +/- 1.39 (6 h) and 5.98 +/- 1.17 (24 h) and max. abscess/blood ratios were
      6.22 +/- 1.41, 4.09 +/- 0.84 and 0.914 +/- 0.351 all at 24 h for 99mTc(V) DMSA,
      99mTc(III) DMSA and 99mTc-HIG, respectively. Experimental arthritis was produced
      in New Zealand white rabbits by intra-articular injection of ovalbumin. Four days
      later 37 MBq of 99mTc(V) DMSA and 99mTc-HIG were each i.v. administered to 3
      rabbits. Scintigrams obtained at 1, 3, 6, and 24 h clearly demonstrated arthritic
      joints. ROI's over arthritic joints were compared to contralateral normal joints
      (A/C). The max. A/C ratios were 2.10 +/- 0.31 (3 h) and 2.92 +/- 0.99 (24 h) for
      99mTc(V) DMSA and 99mTc-HIG, respectively. Our results indicated the feasibility
      of imaging inflammatory lesions with 99mTc(V) DMSA.

PMID- 9006731
TI  - A case of malignant fibrous histiocytoma of the ilium, evaluation by blood-pool
      scintigraphy.
AB  - A rare case of malignant fibrous histiocytoma (MFH) of the ilium was presented
      and blood-pool scintigraphic images and angiographic images were correlated.
      Hypervascular tumor and lacking of contrast material with arteriovenous shunts
      were shown by angiography. Intensive tracer accumulation was shown by blood-pool
      scintigraphy. After radiation therapy and transcatheter arterial embolization of
      the tumor, tracer accumulation was noticeable reduced. These findings suggested a
      vascular tumor such as angiosarcoma, but surgery revealed MFH of the bone. Blood
      pool scintigraphy was useful in the evaluation of the vascular characteristics of
      the tumor.

PMID- 9006730
TI  - Metastatic calcification: accumulation of a bone tracer during dynamic data
      acquisition.
AB  - Metastatic calcification is often detected by bone scintigraphy. We recently saw
      metastatic calcification in the stomach and kidneys of a patient on continuous
      ambulatory peritoneal dialysis. Tc-99m HMDP accumulation into both organs was
      noted even in the first frame of dynamic data acquisition of 4 min/frame,
      suggesting that calcium deposits may create an aggressive process and we may
      obtain information on the calcium deposit rate to better understand the mechanism
      of metastatic calcification.

PMID- 9006732
TI  - Treatment of radioiodine-negative bone metastasis from papillary thyroid
      carcinoma with percutaneous ethanol injection therapy.
AB  - A 62-year-old woman with metastatic papillary thyroid carcinoma in the sternum
      was successfully treated with percutaneous ethanol injection therapy (PET) when
      previous radioiodine therapy and external irradiation were ineffective. The
      patient tolerated the treatment well and the refractory pain in the anterior
      chest wall that was alleviated with morphine prior to PEIT completely
      disappeared. No severe complications were observed. PEIT was performed 4 times (2
      times with ultrasound guidance and 2 times with CT guidance). The posttreatment
      CT scan and 201Tl scintigraphy demonstrated significant decrease in the tumor
      volume. The serum thyroglobulin level fell to less than one-twentieth of the
      pretreatment value. It is suggested that PEIT has a value in treating bone
      metastasis from thyroid carcinoma which do not respond to radioiodine.

PMID- 9006733
TI  - Absent myocardial I-123 BMIPP uptake in a family.
AB  - A 72-year-old woman with hypertension showed no sign of myocardial accumulation
      of 123I-BMIPP, and 201Tl and 123I-MIBG scintigraphy demonstrated normal findings.
      Electrocardiography showed left axis deviation with inverted T waves in leads I,
      aVL, V2-6 and QT prolongation. Coronary arteriography, two dimensional echo
      cardiography and laboratory data showed no abnormality. Her 66-year-old sister
      with non-insulin-dependent diabetes mellitus also had no myocardial BMIPP uptake,
      but had normal 201Tl finding. ECG and chest film findings were normal. Laboratory
      data indicated slightly high fasted blood glucose, triglyceride and total
      cholesterol. Four sons of a 72-year-old woman also underwent BMIPP scintigraphy.
      No BMIPP uptake was also observed in her 2nd son (49 years old) and his
      electrocardiogram showed QT prolongation. Since these rare findings indicating no
      myocardial BMIPP uptake were seen in a family, we suspected that a hereditary
      myocardial metabolic abnormality accounted for them.

PMID- 9006734
TI  - 99mTc-DTPA-HSA uptake in a case of splenic hamartoma.
AB  - Primary splenic tumors are very rare. The authors present a case of splenic
      hamartoma in which positive 99mTc-DTPA-HSA uptake was recognized with ultrasound,
      CT, MR and angiographic images. This case showed the need to consider hamartoma
      as well as hemangioma in the differential diagnosis of 99mTc-DTPA-HSA uptake in
      splenic tumors.

PMID- 9006736
TI  - Euthanasia, physician-assisted suicide and palliative care.

PMID- 9006735
TI  - New drugs to block tumor's blood supply.

PMID- 9006737
TI  - Genetic testing may prevent hereditary nonpolyposis colorectal cancer. Hamilton
      Fairley Lecture, held at the ESMO Congress, Vienna, November 2-5, 1996.

PMID- 9006738
TI  - Immunotherapy of metastatic renal cell cancer.

PMID- 9006739
TI  - Factors influencing response rates for advanced colorectal cancer chemotherapy.
AB  - BACKGROUND: The activity of various chemotherapy regimens used in the treatment
      of advanced colorectal cancer is assessed by different groups of investigators
      and in various trials by what appear to be common criteria. However, there may be
      substantial inter-trial variation in the interpretation and application of these
      criteria which contributes to differences in response rates reported for the same
      regimen. MATERIALS AND METHODS: This paper reviews the most prominent studies in
      this field and examines the factors which may influence the assessment of
      activity in clinical trials such as patient selection, the definition and
      application of response criteria, the methods of assessment of time to
      progression and duration of response, factors related to the therapeutic regimen
      and statistical methods. Each factor is critically discussed. RESULTS: The
      analysis confirms that there is a large variability among the different studies
      and that an inter-trial comparison is often impossible, with subsequent
      difficulties for clinicians in determining the true impact of therapies.
      DISCUSSION: After briefly commenting on the various issues, this review makes
      recommendations about how to achieve consistency among trials, for instance by
      using standard criteria, by extending the use of randomization even in phase II
      trials and by evaluating high quality, well conducted clinical trials in a meta
      analysis, thereby making possible comparison across trials. The conclusions,
      although specific to colorectal cancer, are also applicable to other advanced
      malignancies.

PMID- 9006740
TI  - Attitudes toward euthanasia of physician members of the Italian Society for
      Palliative Care.
AB  - BACKGROUND: The problems related to requests for euthanasia by terminal patients;
      the variations in attitude of palliative care physicians and the possibility that
      availability of the best palliative care might obviate the problem by eliminating
      requests for euthanasia, are under discussion. DESIGN: A mailed survey with no
      possibility of follow-up of all 685 physician members of the Italian Society for
      Palliative Care (SICP) in 1994. RESULTS: Of the 359 (52.4%) responders, 139 (39%)
      had received requests for euthanasia; 16 of them (4% of the responders but 11.5%
      of those who received requests) had complied at least once, while 216 (60%) had
      not; 125 (35%) thought that euthanasia was 'wrong' under all circumstances; 115
      (32%) thought that situations could occur, even in the context of palliative
      care, in which euthanasia might be ethically 'correct'; 185 (52%) thought that
      the best palliative care might solve the problem of euthanasia, while 109 (30%)
      believed otherwise. The variable most strongly associated with a negative
      attitude toward euthanasia and with the opinion that the best palliative care
      might be a solution to the problem is religious belief (P < 0.0001). CONCLUSIONS:
      The attitudes of physicians practising palliative care in Italy are not different
      from those reported by previous studies which investigated the attitude of other
      health professionals. There was no agreement about whether the best palliative
      care might reduce requests for euthanasia by terminal patients.

PMID- 9006741
TI  - Re-irradiation with concomitant chemotherapy of unresectable recurrent head and
      neck cancer: a potentially curable disease.
AB  - PURPOSE: The purpose of this study was to review the outcome following
      concomitant chemoradiation therapy in previously irradiated patients with locally
      or regionally recurrent or persistent head and neck cancer considered
      unresectable for cure. METHODS AND MATERIALS: We identified 45 patients treated
      between 1986 and 1993 with unresectable locally or regionally recurrent disease
      who were treated on one of four concomitant chemoradiotherapy phase I/II studies
      at the University of Chicago. All patients received hydroxyurea (HU), 5
      fluorouracil (5-FU) and concomitant radiation therapy on an alternate week
      schedule (FHX). Cisplatin was added to FHX in three of the studies. RESULTS: The
      overall survival, progression-free survival, and local/regional control at 5
      years was 14.6%, 13.5% and 20%, respectively, in a cohort of patients whose
      disease is almost universally fatal. Fatal treatment related complications were
      observed in 5 (11%) of patients. Two of these complications were related to
      radiation therapy. Stepwise Cox regression analysis revealed that dose and
      protocol were significantly correlated with survival, progression-free survival
      and local/regional control. A direct correlation was observed with radiation dose
      and an inverse correlation was observed with the initial FHX dose escalation
      study. The 2-year survival was 35% in patients receiving over 58 Gy compared to
      8% for those receiving less than 58 Gy. CONCLUSIONS: Our results show that
      aggressive re-irradiation with concomitant chemotherapy of recurrent head and
      neck cancer results in the cure of some patients with acceptable toxicity if
      tumoricidal doses are applied. These results are in contrast to historical series
      of chemotherapy alone which results in limited palliation of brief duration and
      almost no chance of cure. Thus, re-irradiation with concomitant chemotherapy
      should be further investigated as an alternative to chemotherapy alone in multi
      center or cooperative group randomized trials.

PMID- 9006742
TI  - Combined modality treatment with a weekly brief chemotherapy (ACOP-B) followed by
      locoregional radiotherapy in localized-stage intermediate- to high-grade non
      Hodgkin's lymphoma.
AB  - BACKGROUND: A cooperative study was undertaken to evaluate the efficacy and
      toxicity of a very brief course of chemotherapy followed by locoregional
      radiotherapy in patients with localized-stage intermediate- to high-grade non
      Hodgkin's lymphoma (NHL). PATIENTS AND METHOD: From January 1988 to November
      1994, 84 patients with localized stages IA and IIA intermediate- to high-grade
      NHL underwent a combined modality treatment. All patients underwent a six-week
      chemotherapy regimen, ACOP-B (doxorubicin 50 mg/sqm and cyclophosphamide 350
      mg/sqm on weeks 1, 3, 5; vincristine 1.4 mg/sqm and bleomycin 10 mg/sqm on weeks
      2, 4, 6; prednisone 50 mg p.o. daily throughout the first two weeks and
      thereafter every other day), followed by locoregional radiotherapy (36 Gy).
      RESULTS: The median age was 58 years, with 35% older than 65 years; 52 patients
      had stage I and 32 stage II; 39 patients had extranodal +/- nodal involvement,
      and 4 had testicular involvement. Treatment was well tolerated, with only 38%
      suffering from mild mucositis and no toxic deaths. Seventy-nine patients achieved
      CR after ACOP-B and 83 at the end of the program. With a median follow-up of four
      years, relapse-free survival was 79% with 15 relapses (93% disseminated). Two
      patients with testis lymphoma had CNS relapses. Overall survival was 90% at four
      years. CONCLUSION: This combined program is effective and probably curative in
      localized stage intermediate- to high-grade NHL, with low toxicity, also in
      elderly people. Patients with NHL of the testis, as primary site, require CNS
      prophylaxis due to the high likelihood of CNS relapse.

PMID- 9006744
TI  - Probability of long-term disease-free survival for acute myeloid leukemia
      patients after first relapse: A single-centre experience.
AB  - BACKGROUND: Various polichemotherapy regimens, including either high- or
      intermediate-dose Ara-C, are generally utilized to reinduce remission in relapsed
      AML patients. After achieving second CR, bone marrow transplantation (either
      allogeneic or autologous) represents the treatment of choice for eligible
      patients, with the aim of prolonging remission duration and improving disease
      free survival. PATIENTS AND METHODS: Fifty AML patients in first hematological
      relapse were treated with MEC regimen, consisting of a 6-day induction cycle
      [mitoxantrone 6 mg/m2/day, cytarabine (Ara-C) 1 g/m2/day and VP-16 80 mg/m2/day]
      followed by a 4-day cycle with the same drugs for patients achieving complete
      remission (CR); allogeneic or autologous bone marrow transplantation (BMT) were
      planned as post-consolidation treatment. RESULTS: Thirty-four patients (68%)
      achieved second CR, 3 (6%) died during induction and 13 were refractory. CR rate
      was significantly higher in patients with a first CR lasting > 6 months (82% vs.
      41%, P < 0.001). Out of the 34 patients in CR after the 4-day cycle, 18 (53%)
      were not eligible to transplant and did not receive any further therapy and 16
      (47%) received autologous (15 cases) or allogeneic (1 case) BMT at a median time
      of 2 months from second CR. Twenty-two patients relapsed after a median time of 6
      months (range 1-31), 1 patient died from transplant-related toxicity and 11 are
      in continuous CR [7 out of 16 (44%) in the transplanted and 4 out of 11 (36%) in
      the non-transplanted group]. Overall survival and event-free survival for the 50
      patients were 29% and 19% at 70 months, respectively. The disease-free survival
      for the 34 patients who obtained second CR is 29% projected at 69 months [41% at
      69 months for 16 transplanted patients versus 18% at 49 months for the remaining
      18 patients (P = 0.007)]. CONCLUSIONS: These results show that MEC followed by
      high-dose post-consolidation treatment is a promising approach in relapsed AML;
      however, alternative strategies are to be investigated for the relevant fraction
      of patients that, even achieving second CR, are not eligible for BMT.

PMID- 9006743
TI  - Alternating chemotherapy and radiotherapy for limited-stage intermediate and high
      grade non-Hodgkin's lymphomas: long-term results for 96 patients with tumors > 5
      cm.
AB  - BACKGROUND: The role and timing of radiotherapy for optimal treatment of
      localized aggressive non-Hodgkin's lymphoma (NHL) is controversial. We report the
      long-term results of a single-institution pilot study of alternating chemotherapy
      (CT) and radiotherapy (RT) in patients with clinical stages I or II tumors
      exceeding 5 cm. PATIENTS AND METHODS: From 1981 to 1992, 96 patients with stages
      I-II aggressive NHL received an alternating regimen of CT and RT consisting of 8
      cycles of CT with 3 courses of RT interjected after the 2nd, 3rd and 4th cycles
      of CT. The CT combined cyclophosphamide, doxorubicin, teniposide and prednisone
      every 28 days. Each RT course was started 8 to 10 days after CT (15 Gy in 6
      fractions to initially involved and contiguous areas). RESULTS: The median age
      was 54 years. The disease predominantly located in the head and neck area was
      stage II in 63% of patients. Bulky tumors (10 cm or larger) were found in 24% of
      patients. Six patients discontinued CT because of acute toxicity (mucositis). The
      mean relative dose intensity achieved for doxorubicin, cyclophosphamide and
      teniposide were 72%, 82%, and 78%, respectively. Late toxicity consisted mostly
      of severe xerostomia lasting more than 2 years in 7 patients irradiated in
      Waldeyer's ring. The complete response (CR) rate was 91%; 20 of the 86 patients
      in CR relapsed (3 locally only). The median follow-up was 61 months, and at 5
      years, overall survival (OS) was 77%. Classification according to the
      International Prognostic Factor Index was possible for 54 patients, all but three
      of whom were in the 'low risk' group (0-1 factor). Bulky disease was the only
      unfavorable prognostic factor (P < 0.001) for CR, freedom from progression (FFP)
      and OS rates; the low relative dose intensity of CT achieved in this study did
      not affect outcome. CONCLUSION: Alternating chemo-radiotherapy for localized
      aggressive NHL was feasible and yielded long-term results comparable to those
      obtained with standard treatments, despite a reduction in dose intensity
      considerably below that of CHOP which suggested synergistic effects of CT and RT
      in this scheme.

PMID- 9006745
TI  - A phase I study of pentosan polysulfate sodium in patients with advanced
      malignancies.
AB  - BACKGROUND: Pentosan polysulfate (xylanopolyhydrogensulfate) is a semi-synthetic
      sulfated heparinoid polysaccharide which has been used as an anticoagulant for
      nearly thirty years in Europe. It antagonizes the binding of bFGF to cell surface
      receptors and has thus been evaluated for antitumor activity in several animal
      models and human tumor cell lines. In two angiogenic models pentosan has been
      shown to inhibit bFGF stimulation of angiogenesis. Previous clinical studies have
      determined the coagulation effects of pentosan to be the dose-limiting toxicity.
      PATIENTS AND METHODS: We conducted a phase I study designed to define the
      duration-limiting toxicity associated with progressive prolongation of a
      continuous intravenous infusion (three, five, and eight weeks). This study was
      not designed to escalate the dose of pentosan beyond that required to maintain
      the activated partial thromboplastin time (aPTT) between 1.8 and 2.2 times the
      baseline value. RESULTS: Thirteen patients with advanced stage metastatic cancer
      were enrolled (median age 50 years, range 34 to 61 years). Four patients were
      treated in cohort #1 (three weeks of infusional therapy), five patients were
      treated in cohort #2 (five weeks of therapy), and four patients in cohort #3
      (eight weeks of therapy). All patients experienced a progressive prolongation of
      their aPTT and PT. Furthermore, all patients experienced at least grade I
      thrombocytopenia. Other complications were, in general, mild. One patient
      developed grade III liver abnormalities while receiving the eight-week infusion
      and another patient developed grade IV thrombocytopenia while receiving the same
      regimen. One patient with colon cancer had stable disease for 24 weeks, while the
      remaining 12 patients had no objective evidence of response. CONCLUSION: Pentosan
      was well tolerated when doses were adjusted for aPTT prolongations and a five
      week cycle appeared to be the maximum tolerated duration of infusion (initially 4
      mg/kg/day). One patient had stable disease, but there was no objective tumor
      response noted in the remaining 12 patients.

PMID- 9006746
TI  - A multicentre, double-blind study comparing placebo, ondansetron and ondansetron
      plus dexamethasone for the control of cisplatin-induced delayed emesis.
      Ondansetron Delayed Emesis Study Group.
AB  - BACKGROUND: The purpose of this study was to investigate the efficacy and safety
      of oral ondansetron, given alone or in combination with dexamethasone in the
      control of cisplatin-induced delayed emesis. PATIENTS AND METHODS: This was an
      international, multicentre, double-blind, randomised, placebo-controlled,
      parallel group study. A total of 640 chemotherapy-naive patients received
      ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. for the control of acute
      emesis prior to cisplatin (> or = 70 mg/m2) on day 1. Patients who were not
      rescued or withdrawn on day 1 were to be randomised 24 hours after the start of
      cisplatin administration to one of four groups; group I placebo oral (p.o.),
      twice daily (bd) on days 2-6 (n = 125); group II ondansetron (8 mg p.o. bd) on
      days 2/3 followed by placebo (p.o. bd) on days 4-6 (n = 199); group III
      ondansetron (8 mg p.o. bd) on days 2-6 (n = 214); group IV ondansetron (8 mg p.o.
      bd) plus dexamethasone (4 mg p.o. bd) on days 2-6 (n = 66). RESULTS: On day 1,
      81% of patients had complete control of acute emesis, with 68% having no emesis
      and no nausea. Over days 2/3 and over days 2-6, significantly more patients
      receiving ondansetron plus dexamethasone (group IV) reported no emesis and no
      nausea (49% and 45%, respectively) compared to ondansetron alone (32% and 27%,
      respectively) or placebo (group I; 33% and 27%, respectively; P < 0.05 for all
      pairwise comparisons). There were no significant differences in the control of
      emesis over days 2/3, where 61% of patients had complete emetic control (0 emetic
      episodes) with ondansetron plus dexamethasone (group IV), 54% with ondansetron
      (groups II + III) and 49% with placebo (group I). In the distribution of nausea
      grades, ondansetron plus dexamethasone (group IV) was significantly superior to
      ondansetron (groups II + III); P = 0.037) and placebo (group I; P = 0.013) over
      days 2/3. Over days 2-6 there were no significant differences in the control of
      emesis, however a comparison of the distribution of nausea grades over days 2-6
      showed ondansetron plus dexamethasone (group IV) to be significantly superior to
      ondansetron (group III; P = 0.043) and placebo (group I; P = 0.024). All
      treatments were well tolerated and no unexpected drug-related adverse events were
      reported. There were no differences in the overall incidence of adverse events
      between the active treatment groups or placebo. Constipation and headache,
      recognised side effects of 5-HT3 receptor antagonists, were the most commonly
      reported adverse events with the incidence of constipation with ondansetron alone
      (group III) being significantly greater than with over days 2-6 (14% vs. 6%; P =
      0.030). CONCLUSION: In contrast to some previous investigations, in this study,
      ondansetron alone appears to have a minor role in the control of cisplatin
      induced delayed emesis and nausea. In conclusion, the combination of oral
      ondansetron plus dexamethasone is superior to ondansetron and to placebo.

PMID- 9006747
TI  - Clonal analysis of a B-cell lymphoma with recurrent spontaneous remissions and
      evolution into chronic lymphocytic leukaemia.

PMID- 9006748
TI  - Final results of a randomised trial comparing 'Tomudex' (raltitrexed) with 5
      fluorouracil plus leucovorin in advanced colorectal cancer. "Tomudex" Colorectal
      Cancer Study Group.

PMID- 9006749
TI  - Effect of granulocyte colony-stimulating factor administration in elderly
      patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin
      combination chemotherapy regimen. Groupe d'Etudes des Lymphomes de l'Adulte.
AB  - PURPOSE: Results of a multidrug chemotherapy regimen consisting of
      cyclophosphamide, pirarubicin, teniposide, and prednisolone (CTVP) plus
      subcutaneous granulocyte colony-stimulating factor (G-CSF) in elderly patients
      with aggressive non-Hodgkin's lymphoma (NHL) are reported. PATIENTS AND METHODS:
      Between January and December 1992, 46 previously untreated patients older than 69
      years with intermediate- and high-grade NHL received cyclophosphamide 750 mg/m2,
      teniposide 75 mg/m2, pirarubicin 50 mg/m2 day 1, and prednisolone 40 mg/m2 days 1
      to 3. G-CSF, 5 micrograms/kg/day, was administered from day 4 up to day 14 or
      when the absolute neutrophil count reached 5 x 10(9)/l. Six cycles were scheduled
      every 3 weeks. RESULTS: Grade 3 or grade 4 neutropenia complicated 22% and 26% of
      chemotherapy cycles, respectively. Fever or/and clinical infection were observed
      in 4% and 14% of cycles. One toxic death related to a septic shock occurred.
      Eight cycles (4%) were delayed with a median duration of 7 days. Administered
      median dose intensity was 93.5%. Objective response rate was 74% and 46% of the
      patients achieved a complete response. The 2-year overall survival and event-free
      survival rates were 47% and 28%. CONCLUSION: In comparison with a previous group
      of patients treated with CTVP, G-CSF allows delivery of chemotherapy with a
      reduced neutropenia-induced morbidity in an outpatient setting in elderly
      patients with aggressive NHL without modifying response rate or survival.

PMID- 9006750
TI  - Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma.
AB  - BACKGROUND: To assess the activity of single agent vinorelbine in pretreated non
      Hodgkin's lymphoma. PATIENTS AND METHODS: Twenty-three pretreated patients with
      non-Hodgkin's lymphoma (14 intermediate-high grade, nine low-grade) were treated
      with vinorelbine 30 mg/m2/week for six months or up to four doses after achieving
      CR. RESULTS: Among 13 evaluable patients with intermediate-high grade lymphoma,
      three obtained CR and three PR, for an overall response rate of 46% (95% CI: 19%
      75%). Median duration of response was six months. Otherwise, vinorelbine did not
      show any significant activity inn chemotherapy-refractory low-grade non-Hodgkin's
      lymphoma. Toxicity was acceptable, and the drug was well-tolerated even in
      elderly patients. CONCLUSIONS: The good activity and tolerability of vinorelbine
      in relapsed intermediate-high grade lymphoma suggest its inclusion in first-line
      regimens, especially in elderly patients.

PMID- 9006751
TI  - Acute pulmonary toxicity associated with high-dose vinorelbine and mitomycin C.

PMID- 9006752
TI  - The Rosai-Dorfman syndrome in a 17-year-old woman with transformation into high
      grade lymphoma. A rare disease presentation.

PMID- 9006753
TI  - Adjuvant therapy for breast cancer and psychological distress.

PMID- 9006754
TI  - Rapid intravenous premedication with dexamethasone prevents hypersensitivity
      reactions to paclitaxel.

PMID- 9006755
TI  - The adverse effects of sectioning the posterior cruciate ligament in rabbits.
      Changes in the structural and morphological properties of the femur-anterior
      cruciate ligament-tibia complex.
AB  - This study examined the changes in the structural properties of the femur
      anterior cruciate ligament-tibia complex (FATC) and the histologic changes of the
      anterior cruciate ligament (ACL) following sectioning of the posterior cruciate
      ligament (PCL) of 20 rabbits. The PCL in the right knee was sectioned through an
      arthrotomy. The left knee underwent arthrotomy only and was used as a control.
      The animals were killed 3 and 6 months postoperatively. The tensile properties of
      the FATCs were tested, and the ACLs were histologically examined using polarized
      light microscopy and transmission electron microscopy. There were significant
      decreases in the ultimate load following sectioning of the PCL, although there
      were no significant changes in the stiffness. There were no significant
      differences in either the crimp period or the crimp amplitude of the ACL
      following sectioning of the PCL. There were significant increases in the number
      of collagen fibrils per square micrometer, and significant decreases in the
      collagen fibril diameter and proportion of total collagen fibril area per square
      micrometer following sectioning of the PCL. These findings suggest that isolated
      PCL injury may cause pathological changes in the ACL and its insertion sites.

PMID- 9006756
TI  - The clinical diagnosis and results of conservative treatment of knee distortion
      injury.
AB  - Distortion of the knee joint is a considerable trauma even when the knee is
      primarily stable. Of 50 patients, 30% displayed symptoms or signs 2 months after
      the injury and 36% on subsequent examination an average of 5.6 years later. In a
      repeat clinical examination one anterior cruciate ligament rupture was not
      confirmed at the primary stage (2%). For assessment of stability and extent of
      injury, the repeat clinical examination proved reliable. Ruptures of the meniscus
      were noted in 18% of the patients in connection with the primary injury. Of those
      who underwent a meniscus operation, 27% had further operations and, four patients
      of 50 had another operation as a result of a new trauma. Thus, a total of 25% of
      the patients required surgery. The material is biased as I sought to exclude
      ligament ruptures in the first instance. No patient was permanently incapacitated
      from work. A large portion of the later symptoms were connected with the
      patellofemoral joint or with the postoperative condition. Bandaging did not
      affect the resulting recovery rate. Regular exercise of the thigh muscles
      prevented the onset of quadriceps atrophy, but there was a clear deterioration in
      the condition of the muscles in the early stages.

PMID- 9006757
TI  - Survival of Lubinus straight (IP) and curved (SP) total hip prostheses in 543
      patients after 4-13 years.
AB  - The clinical outcome and survival of 543 total hip arthroplasties with Lubinus
      cemented total hip prostheses after a mean of 7.9 years are reported. Clinical
      evaluation revealed no significant differences between patients with a straight
      stem and those with a curved anatomic stem. Loosening was statistically
      associated with young age, male sex, heavy weight, diagnosis other than
      osteoarthritis and year of operation. Survivorship analysis of the Lubinus IP
      implant at 8 years revealed a 95% chance of survival. The survival of the SP
      implant was 96%. After this time point the curve for SP implants began to fall at
      a faster rate than that for IP implants.

PMID- 9006758
TI  - Clinical and sonographic evaluation of the risk of rupture in the Achilles
      tendon.
AB  - Chronic pain in the region of the Achilles tendon is a common problem and often a
      sign of progressive degeneration of the tendon which may lead to its rupture. We
      studied the clinical course and sonograms in 36 patients with achillodynia to
      find a prognostic parameter enabling us to estimate the risk of rupture. The
      patients were evaluated clinically for swelling and tenderness and by high
      resolution real-time sonography. The sonograms were graded according to the
      tendon thickness as normal (< 6 mm), minimal (6-8 mm), moderate (8-10 mm) to high
      grade (> 10 mm) in the sagittal diameter of the transverse section, and
      alterations of echotexture were described as diffuse, circumscribed, or
      inhomogenous. At the time of the primary investigation, we found thickening and
      alterations of the echotexture in 33 of 72 tendons. In 48 tendons we found pain
      and local or diffuse swelling in the Achilles tendon region (sensitivity 0.58,
      specificity 0.79). After a follow-up of 48 +/- 8 months, 7 tendons had ruptured
      spontaneously. Analysis of the sonograms of the patients taken prior to the
      rupture showed a high-grade thickening in 4 cases, moderate thickening in 2
      cases, and a diameter between 6 and 8 nm in one patient. In no case did we find a
      rupture of a tendon primarily classified as normal. Patients without sonographic
      changes exhibited a significantly better clinical outcome following conservative
      treatment. Sonography was found to be a valuable tool for determination of the
      tendon's thickness and echotexture. In 28% of our patients with thickening,
      circumscribed lesions of the echotexture, and chronic pain, a spontaneous rupture
      occurred.

PMID- 9006759
TI  - Vascular anatomy of the ovine anterior cruciate ligament. A macroscopic,
      histological and radiographic study.
AB  - Sheep are being extensively utilized in animal models for orthopaedic research,
      but the vascular anatomy of their anterior cruciate ligament (ACL) has not yet
      been thoroughly described. This study demonstrates the blood supply to the ACL.
      Vascular injection with plastogen G, lead oxide and India ink was performed in 12
      back limbs of Styrian mountain sheep, and gross observations, microradiography
      and routine histology were done. The large vessel and the microvascular anatomy
      are similar to those described for humans. The middle genicular artery and the
      descending genicular artery contribute vessels that supply the ACL.
      Epiligamentous vascular plexuses give off capillaries which penetrate the
      ligament substance and supply numerous, longitudinally oriented intraligamentous
      vessels. These findings make the Styrian mountain sheep a potential animal model
      for biologic investigations of ACL pathology.

PMID- 9006760
TI  - Quality of life after pelvic ring injuries: follow-up results of a prospective
      study.
AB  - A follow-up after 2 years on average could be done in 43 cases of pelvic ring
      injuries. Seven were type A, 8 type B and 28 type C lesions. Every type A lesion
      was treated non-operatively. External fixation and non-operative management were
      used with type B injuries. As well as non-operative treatment, both internal and
      external surgical techniques were employed for type C fractures. While group A
      hardly mentioned pain in the follow-up, groups B and C suffered dorsal pelvic
      pain of comparable intensity irrespective of the therapeutic measures taken.
      Anatomic reduction does not guarantee freedom from pain. We also rated hip joint
      flexibility and ability to walk according to the Merle D'Aubigne score. Because
      of their pelvic injuries 50% of the type C patients changed their profession. The
      sequelae of the accident on sports and leisure time activities will be considered
      as well as the subjective contentment evaluated. Unstable and dislocated pelvic
      ring injuries permanently interfere to a high degree with the quality of life. It
      is remarkable that many of the traumatic lesions which interfere with the quality
      of life are caused by the traumatic violence itself and cannot be influenced by
      the manner of surgical stabilization.

PMID- 9006761
TI  - Internal hemipelvectomy and endoprosthetic pelvic replacement: long-term follow
      up results.
AB  - We report on our experiences with internal hemipelvectomy followed by an
      implantation of a endoprosthetic pelvic replacement (EPR) performed in 15
      patients over a period of 15 years. Our primary aim was to determine the
      implications for this procedure because of its high rate of complications. Due to
      the malignant character of the disease and the biomechanical stress on the
      anatomical region, the demands on the surgeon are high. The most important factor
      is a sufficiently wide resection of the primary tumour because most are
      chondrosarcomata which do not respond to other therapies. In addition, the
      malignant character of the tumour has the greatest influence on the long-term
      results. Internal hemipelvectomy and endoprosthetic pelvic replacement are
      accompanied by a high rate of operative and postoperative complications
      Nevertheless, nearly full anatomical and functional reconstruction can be
      obtained provided a medium level of function is accepted. Follow-up results of
      the remaining six still living patients were evaluated by means of three
      different scoring systems. All patients had only a medium score but emphasised
      subjective acceptance of the endoprosthetic pelvic replacement even when removal
      was necessary later on. Because of the lower functional outcome of alternative
      operative procedures such as pseudarthroses and arthrodeses and problems with the
      replantation of autoclaved autografts or implantation of an allograft, internal
      hemipelvectomy combined with endoprosthetic pelvic replacement is the treatment
      of choice for these specific acetabular lesions, provided a complete resection is
      feasible. Otherwise, an external hemipelvectomy is necessary because even
      alternative limb-salvaging procedures must incorporate the same complete
      resection of the tumour. In cases of metastatic lesions, internal hemipelvectomy
      and endoprosthetic pelvic replacement are indicated relatively because of the
      systemic character of the disease. The procedure should be considered only when
      resection of a solitary metastasis enables a cure and/or prolongation of life
      with an improved quality of life.

PMID- 9006762
TI  - Sequential intramedullary nailing of open tibial shaft fractures after external
      fixation.
AB  - We reviewed 32 tibial shaft fractures in 31 patients treated with sequential
      intramedullary nailing after primary external fixation. There were 30 open
      fractures and 2 closed injuries with severe blunt trauma requiring fasciotomy.
      Fifty per cent of the fractures were classified as Gustilo type III A and B
      injuries. The mean external fixation treatment averaged 6.6 weeks, and secondary
      intramedullary nailing was done on average 7.4 weeks after injury. In 50% of the
      fractures, secondary nailing was done at the same procedure as removal of the
      external fixation. Overall, the incidence of osteomyelitis and non-union was 3.1%
      each and of malunion 19%. The time to full weight-bearing averaged 31.2 weeks.
      The results were separately analyzed according to Gustilo types and subtypes. In
      the Gustilo type III B injuries, the incidence of osteomyelitis and non-union was
      11%, while malunion occurred in 33%. The time to full weight-bearing averaged 53
      weeks. These results support the conclusion that this treatment modality is a
      valid alternative to other treatment options. However, previous pintract
      infections should be regarded as a contraindication for secondary nailing.

PMID- 9006763
TI  - Effects of single high-dose vitamin D3 on fracture healing. An ultrastructural
      study in healthy guinea pigs.
AB  - The benefits of vitamin D3 on fracture healing have been commonly demonstrated in
      vitamin-D3-depleted animal models. The aim of this study was to examine the
      effects of a single high dose of vitamin D3 on fracture healing in a healthy
      animal model, which has not been previously reported. Twenty healthy young adult
      guinea pigs were randomly divided into groups as 'control' and 'vitamin D', and
      their right tibias were fractured with digital manipulation. Guinea pigs in
      vitamin D group were injected intramuscularly with 50,000 i.u./kg of vitamin D3.
      The animals were killed at 7, 14, 21 and 28 days following fracture.
      Ultrastructural analysis of the harvested tibias revealed that a single high dose
      of vitamin D3 stimulated fracture healing. The observed effects at the fracture
      zone in a healthy animal model included advancement of blood supply, acceleration
      of synthesis and organization of collagen fibres, acceleration of the
      proliferation and differentiation of osteoprogenitor cells, and activation of the
      mineralization of the matrix.

PMID- 9006764
TI  - The mechanism of loosening in cemented hip prostheses determined from long-term
      results.
AB  - Analysis of the mechanisms of loosening of cemented stems by radiological long
      term follow-up in 129 cases. The most important finding was the failure of the
      cement-metal interface (29.5%), which was correlated significantly with
      osteolysis (31%). This suggests that the polyethylene debris reaches the bone
      through defects in the cement mantle (76.7%). In fact, the appearance of cement
      defects matches the number of identified osteolyses. This study shows that no
      permanent fixation can be achieved by the surface roughness of 2.0 microns Ra
      tried herein.

PMID- 9006765
TI  - Recurrent dislocation of the patella and the Goldthwait operation.
AB  - In this study 17 patients with recurrent dislocation of the patella were followed
      up 10 years after their Goldthwait operation. The subjective and clinical
      findings were excellent or good in 70%. X-radiographs indicated osteoarthritis of
      the femoropatellar joint in 60%. Concerning the aetiopathological factors, we
      found an increased external torsion of the afflicted extremity (measured by
      computed tomography).

PMID- 9006766
TI  - The treatment of Legg-Calve-Perthes disease. To contain or not to contain.
AB  - In order to evaluate a treatment protocol involving a non-containment method and
      femoral osteotomy when lateral subluxation of the femoral head develops, 39
      children with 42 affected hips were examined radiologically an average of 7 years
      (4-16 10/12) following the onset of Legg-Calve-Perthes disease. Twenty-six hips
      were treated conservatively with an ischial-bearing, Thomas-type splint and 16
      with a femoral varus derotating osteotomy. Both Catterall and Herring gradings
      were used. The end result was evaluated according to the Stulberg classification.
      All Catterall grade I (n = 8) hips had a satisfactory result regardless of age at
      onset and method of treatment. In Catterall groups II-IV (n = 34), age at onset
      influenced the treatment outcome. In children affected before the age of 8 years,
      results of conservative treatment were originally satisfactory but were seen to
      deteriorate with advancing age. In children over 8 years old (n = 13), the
      results clearly favour operative containment.

PMID- 9006767
TI  - Results of the Muller acetabular reinforcement ring in revision arthroplasty.
AB  - Between April 1984 and December 1987 a Muller acetabular reinforcement ring was
      employed in 98 revision cases (94 patients). Twenty-two patients died before
      follow-up evaluation. Forty-seven (66%) of the remaining 72 patients (49 of 75
      hips) were examined after a mean of 6.4 years (range 5-9 years). Excluding those
      who died, the postoperative outcome of 69 patients is known. Migration was
      measured according to Sutherland by means of a digitising table. Cup position was
      determined by a new angle (beta) between the sacroiliacal line and a reference
      line. The reference line connects the centre of the femoral head with the
      intersection between the sacroiliacal and obturator lines. Aseptic and septic
      loosening required revision surgery in 2 cases each (4%). The postoperative beta
      angle showed a high correlation with migration (P = 0.001) as well as with
      radiolucencies (P = 0.001). In cases which required further revision, beta
      amounted to 44 deg (craniolateral position), and in stable cases up to 60 deg. A
      lateral and cranial position of a Muller acetabular reinforcement ring leads to
      high loosening rates. The beta angle accurately describes cup position, and its
      postoperative value is highly predictive for loosening.

PMID- 9006768
TI  - Course of bone mineral content changes around cementless Zweymueller total hip
      arthroplasty. A 4-year follow-up study.
AB  - In this prospective study we followed the bone mineral content (BMC) changes over
      time in seven zones of interest around uncemented Zweymueller total hip
      arthroplasty (THA) components, using dual-energy X-ray absorptiometry (DEXA)
      combined with a radiographical analysis of the distal femoral cortices, close to
      the tip of the stem. In 36 women (average age 55 years) operated on for primary
      hip osteoarthritis, BMC of the hips was measured preoperatively and 2 weeks, 1
      year and 4 years postoperatively. In particular, a significant decrease of the
      preoperative values (ranging from 35% to 42.53%; P = 0.05 to 0.01) was noted
      immediately postoperatively in zones 2-7. Thereafter, an additional significant
      increase of BMC was observed between the first and last observations at the
      greater (30%, P < 0.05) and lesser (35.48%, P < 0.01) trochanter. The BMC changes
      over time were not related to the age of the patients. The BMC reduction observed
      immediately after implantation of the Zweymueller THA is probably related to the
      intraoperatively removed bone from (1) the medial and distal inner surface of the
      acetabulum and (2) the inner femoral cortex. Thereafter, the BMC in zones 2, 6
      and 7 remained practically unchanged. The fact that a significantly delayed BMC
      increase was found in the region of the greater and minor trochanter 4 years
      later may be due to an increasing, continuous bone turnover in the
      intertrochanteric area. Thus, the Zweymueller screw socket becomes definitively
      anchored immediately postoperatively in the medial and distal thirds of the
      acetabulum and remains stable over time, whereas the Zweymueller stem is mainly
      anchored within the distal femoral cortex as well as within the mass of the
      greater and minor trochanter, and was still stable at the 4-year follow-up.

PMID- 9006769
TI  - Cartilage-flow phenomenon and evidence for it in perichondrial grafting.
AB  - The cartilage-flow phenomenon has been frequently described but not in connection
      with transplantation procedures for treatment of cartilage lesions. Consequently,
      we examined this particular phenomenon in an experimental sheep model originally
      set up to study the use of perichondrial grafts for repair of full-thickness
      cartilage lesions. Osteochondral lesions were made in nonweight-bearing and
      weight-bearing areas of knee joints in 36 sheep. The defects were filled with
      autologous rib perichondrial grafts and secured by either collagen sponges or
      fibrin glue (n = 24 animals). Defects without perichondrial grafts served as
      controls (n = 12 animals). Following 1 week of immobilisation of the operated
      leg, the plaster was removed, and animals were allowed to move freely. Animals
      were killed after 2, 4, 12 and 16 weeks. Grafts including rims of original
      surrounding cartilage and bone were removed and investigated by means of
      macroscopy, histology and micromorphology, including scanning electron microscopy
      and analysis under polarized light. Cartilage flow was observed in all specimens
      by 4 weeks after drilling the defects, independent of the weight-bearing
      condition. These flow formations exhibited a bending of the collagen fibres
      centrally into the defects, reduction of metachromasia, cell cluster formation
      and areas of reduced cell density. Time-dependent flow formations were observed
      related to the weight-bearing condition and whether or not the defects had been
      grafted. In grafted, non-weight-bearing defects further cartilage flow was
      stopped 8 weeks after transplantation by the growing perichondrial transplants,
      which had filled the defects completely. In contrast, control defects exhibited
      further flow formations in both areas. The same was observed in grafted defects
      in the weight-bearing area. In defects without complete filling as not enough
      spontaneously growing fibrous tissue had arisen from the bottom of the defects,
      two different observations were made: either the defects exhibited a fungiform
      mass of fibrous tissue that had overgrown the lateral flow formations, or the
      central mass of fibrous tissue was overgrown by the lateral flow formations. In
      conclusion, cartilage flow seems to be a mechanically induced phenomenon at the
      rims of cartilage lesions that contributes little to the reduction of size of
      large osteochondral defects. There was no evidence for new cartilage
      proliferation or production of cartilaginous matrix at the rims of the lesions.

PMID- 9006770
TI  - Rotational acetabular osteotomies: a rabbit model.
AB  - We investigated the morphological changes in the articular cartilage after
      rotational acetabular osteotomy in 16 adolescent rabbits. Radiological and
      histological studies were conducted at 12 and 24 weeks postoperatively. The
      radiological evaluations at 12 and 24 weeks showed significantly increased
      femoral head coverage. No cases of osteonecrosis of the acetabulum or femoral
      head nor narrowing of the joint space was observed. The histology of the
      articular cartilage at 12 weeks postoperatively showed cloning and
      hypercellularity of the chondrocytes in the medial portion of the acetabular
      roof, indicating remodelling due to the increased weight-bearing stress caused by
      the osteotomy. The histology at 24 weeks postoperatively showed less cloning of
      the chondrocytes, indicating that the remodelling process in the articular
      cartilage induced by this procedure was almost complete at 24 weeks. Degeneration
      of the articular cartilage was not observed within 24 weeks of the operation.

PMID- 9006771
TI  - Axial computed tomography of the patellofemoral joint with and without quadriceps
      contraction.
AB  - Computed tomography was used to analyze the patellofemoral relationship during
      the first 60 degrees of knee flexion in patients with chronic patellofemoral pain
      syndrome (49 knees) and a healthy control group (15 knees). The patellofemoral
      joints were imaged axially through the center of the patella articular cartilage
      with the knee flexed 0 degrees, 0 degrees with maximal quadriceps muscle
      contraction, 30 degrees, and 60 degrees. In 0 degrees of knee flexion, the sulcus
      angle was greater in the symptomatic group than in normal controls. The patella
      displaced further laterally, and the lateral patellar tilt was greater. The
      patellar lateral index was found to be greater at 0 degrees and indicated severe
      abnormality with full quadriceps muscle contraction. The Laurin angle was
      pathologic with increased medial opening, especially with muscle contraction. At
      30 degrees of knee flexion, these differences were less marked than at 0 degrees.
      No relevant differences were found with 60 degrees of knee flexion. This study
      showed that the sulcus angle, lateral patellar displacement, lateral patellar
      tilt, patella lateral condyle index, and Laurin angle are relevant diagnostic
      features in 0 degrees of knee flexion, indicating a pathological femoral patellar
      gliding mechanism. Our evaluation also demonstrated the influence of full
      quadriceps muscle contraction, especially regarding lateral patellar displacement
      and the Laurin angle, and it was most prominent on the patella lateral condyle
      index. Thus, quadriceps muscle contraction often creates a more pathological
      displacement of the patella, which can be depicted using axial computed
      tomography.

PMID- 9006772
TI  - Cardiac risks in total hip replacement.
AB  - During total hip replacement, identifiable myocardial ischemia occurs
      intraoperatively, indicating myocardial strain. Coronary heart disease (CHD)
      patients are at risk during this type of surgery. Perioperatively, CHD patients
      had significantly longer ST depressions than patients not suffering from CHD
      (3348 min vs 454 min). The number of depression episodes was also significantly
      higher for CHD patients (160 vs 36). Comparing the perioperative with the
      postoperative stage demonstrated that CHD patients experienced a highly
      significant shift towards shorter periods of ST-segment depression
      postoperatively.

PMID- 9006773
TI  - Does the anchorage form and depth influence the pull-out strength of screws from
      bone cement? An experimental study.
AB  - The pull-out strengths of cortical screws inserted into soft, unpolymerised
      Refobacin Palacos bone cement (procedure S) and into hardened polymerised cement
      into which a hole had been drilled and tapped (procedure P) were compared.
      Cortical screws 58 mm in length, outer diameter 4.5 mm and inner diameter 2.95 mm
      were used. Screws were inserted into cement cylinders at 5 mm incremental depths
      between 10 and 30 mm. At a screw depth of less than 25 mm, the screws pulled out,
      and at a depth of greater than 25 mm, the screws broke in both procedures. There
      was no statistically significant difference in pull-out strength leading to burst
      or break between the two procedures for screws inserted to comparable depths, but
      there was a statistically significant difference regarding the screwing depth
      regardless of the procedure of screw insertion chosen. The average material
      stability (sigma) of the cortical screws used was calculated to be 1191 N/mm2,
      and the elasticity limit was 5137 N. This study demonstrated that the material
      stability and not the depth of screw insertion was the limiting parameter in
      screw anchorage in bone cement while static testing. To avoid screw breakage due
      to fatigue during continuous alternate loading, the screws should not be loaded
      above this value.

PMID- 9006774
TI  - To compare and contrast the various evaluation scoring systems after anterior
      cruciate ligament reconstruction.
AB  - In a prospective study we evaluated with eight established scoring systems 56
      patients who received a Leeds-Keio ligament as an anterior cruciate ligament
      replacement. The systems were compared based upon their total results, as well as
      their subjective, objective and functional criteria. It was found that the
      diversity of both the results and criteria within the systems made valid
      comparisons impossible. From this investigation it was concluded that the use of
      an internationally standardized evaluation system would provide the best
      possibility for comparison of surgical results. As a result, we recommend the
      IKDC Score system together with a visual analogue scale to evaluate subjective
      knee complaints.

PMID- 9006775
TI  - Administration of tourniquet. I. Are edema and oxidative stress related to each
      other and to the duration of ischemia in reperfused skeletal muscle?
AB  - One hindlimb of mice was subjected to 60, 90 and 120 min ischemia by application
      of a tourniquet followed by a 60-min reperfusion period. An additional
      experimental group received a tourniquet for 90 min without subsequent
      reperfusion. The soleus muscle (from the contralateral side also as control) was
      removed and evaluated for muscle weight, protein weight, protein content, and
      glutathione concentrations. Ischemia alone without subsequent reperfusion did not
      produce significant changes. With postischemic reperfusion, the protein content
      and muscle weight increased, probably because of an increased capillary
      permeability, leading to muscle edema. Oxidative stress was also present during
      reperfusion, correlating well with the changes in protein content. The intensity
      of these alterations appeared to depend on the period of ischemia.

PMID- 9006776
TI  - Administration of tourniquet. II. Prevention of postischemic oxidative stress can
      reduce muscle edema.
AB  - An experimental group of mice were subjected to a hindlimb tourniquet for 90 min
      followed by 60 min postischemic reperfusion (ischemia/reperfusion, I/R). Two
      further groups with the same experimental procedure received allopurinol to
      inhibit endothelial xanthine oxidase to produce oxygen free radicals (I/R-allo)
      or vitamin E as a radical scavenger (I/R-vitE). The soleus muscle was examined,
      and the contralateral muscle served as control. Glutathione (both reduced and
      oxidized forms, GSH and GSSG) concentrations and the relative protein content
      were measured. Additionally, the muscles were examined under the electron
      microscope for pathological alterations. The results showed: (i) the existence of
      much oxidative stress in the I/R group, but not in the I/R-allo and I/R-vitE
      groups; (ii) an increased protein content indicative for high capillary
      permeability in the I/R group, but not in the I/R-allo and I/R-vitE groups; (iii)
      considerably fewer capillary endothelial disturbances in the I/R-allo and I/R
      vitE groups than in the I/R group. We conclude that allopurinol and vitamin E
      diminished the occurrence of oxidative stress and of edema in postischemic
      skeletal muscle.

PMID- 9006777
TI  - Age-dependent correlation of low-back pain and lumbar disc regeneration.
AB  - The prevalence of lumbar disc degeneration in subjects suffering from low-back
      pain (n = 207; age range 10-49 years) and in age-matched asymptomatic controls (n
      = 216) was investigated by magnetic resonance imaging. The percentage of subjects
      with degenerated discs increased with age; starting from the age of 15 years,
      this increase was more rapid in subjects with low-back pain. Concurrently, the
      number of degenerated discs was higher in the pain group than in controls. Lumbar
      disc degeneration manifests earlier and in a greater percentage of subjects with
      low-back pain than in asymptomatic controls.

PMID- 9006778
TI  - External rotational positioning of the leg after intertrochanteric combined varus
      derotational osteotomy in Perthes' disease.
AB  - A 13-year-old boy underwent an intertrochanteric combined varus derotational
      osteotomy (VDO) for Perthes' disease of his right hip. After surgery he walked
      with his right leg externally rotated. Computed tomography scans of both knees
      and hips were obtained with the legs in their spontaneous position to evaluate
      rotation and anteversion. The femoral condyles were in 28 degrees of external
      rotation on the operated side compared with 2 degrees on the non-operated side.
      The angle between the femoral neck and the horizontal plane was 32 degrees on
      both sides. We conclude that there may be a risk that a derotational osteotomy
      may produce an external rotational position of the leg instead of altering the
      angle between the femoral neck and the horizontal plane.

PMID- 9006780
TI  - Cervical myelo-radiculopathy in athetoid cerebral palsy.
AB  - Cervical myelopathy complicating athetoid cerebral palsy has not been adequately
      highlighted in the literature. We report two cases of patients with athetoid
      cerebral palsy and long histories of involuntary movements who developed cervical
      myelo-radiculopathy. Dystonic athetoid neck movements may cause excessive axial
      neck rotation as well as flexion and extension movements of the spine. These
      repetitive exaggerated movements may result in early degenerative changes of the
      vertebrae which may enhance the myelo-radiculopathy. The two patients were
      treated with combined anterior and posterior fusion with satisfactory results.
      They were bedridden preoperatively but have since started walking with or without
      a cane. We conclude that combined anterior and posterior fusion is the treatment
      of choice for severe myelopathy complicating athetoid cerebral palsy.

PMID- 9006779
TI  - Cervical spinal cord compression in hereditary multiple exostoses. Report of a
      case and a review of the literature.
AB  - Spinal cord compression is an extremely serious complication of hereditary
      multiple exostoses (HME). A case of HME with compression of the cervical spinal
      cord is reported. Complete recovery following surgery was achieved. A review of
      the relevant literature revealed 51 previous cases of HME with cord/cauda equina
      compression. Most patients were under 30 years of age with more men affected than
      women. The family history was positive in 60%. The cervical and thoracic areas
      were predominantly affected, with the symptoms usually developing slowly.
      Recovery following surgery is to be expected in the majority of cases. In
      patients with HME and suffering from neurological symptoms, the possibility of
      spinal cord compression should be considered. Prompt diagnosis and surgical
      excision provide the best prognosis.

PMID- 9006781
TI  - Aneurysmal bone cyst of the terminal phalanx of the thumb in a child.
AB  - We report a case of aneurysmal bone cyst (ABC) of the terminal phalanx of the
      thumb in a young boy, which was treated successfully with complete curettage with
      preservation of the growth plate. Three years later he was asymptomatic, with
      normal growth of the thumb, full range of movement and no evidence of recurrence.
      For this rare benign cyst in a child's hand, we recommend simple surgery to
      preserve the growth plate.

PMID- 9006783
TI  - Antiarrhythmic action of the new calcium antagonist [1,2,5-trimethyl-4-phenyl-4
      beta-(N-cyanoethyl-N-4'-methoxybenzyl) -ethylamino]piperidine dihydrochloride.
AB  - Arrhythmias induced by coronary artery ligation in cats, by CaCl2 and epinephrine
      in rats, and by ouabain in guinea-pigs were used as experimental models for
      studying the effects of a new calcium antagonist AR-1 ([1,2,5-trimethyl-4-phenyl
      4-beta-(N-cyanoethyl-N-4'-methoxybenzyl) -ethylamino]piperidine, calcium channel
      blocker and calmodulin antagonist) on ventricular arrhythmias. Coronary ligation
      caused 90% lethality (ventricular fibrillation) with 12.5 min in untreated
      control cats, which was prevented by administration of AR-1 (4 mg/kg body weight
      (b.w.) before or after arrhythmia induction. Pretreatment with AR-1 afforded
      protection in a dose-related fashion. A dose of 1.5 mg/KG b.w. increased survival
      to 45%, and all cats dosed with 3 to 5 mg/Kg b.w. survived. CaCl2 (180 mg/Kg
      b.w., i.v.) induced ventricular fibrillation and 100% lethality. These effects
      were completely prevented by an anti-arrhythmic dose of AR-1 (3 mg/kg b.w.).
      Epinephrine-induced ventricular arrhythmias were also prevented by the same dose
      of AR-1. AR-1 (5 mg/kg b.w.) did not prevent ouabain (0.5 mg/kg b.w.)-induced
      arrhythmias that caused death within 17 +/- 3.7 min, but displayed protective
      effects during 67 +/- 7.7 min. The results from these animal studies, in
      conjunction with previously studies demonstrating coronarodilatory and anti
      platelet efficacy of this compound, collectively suggest that AR-1 has a
      potential to become a useful antianginal and antiarrhythmic therapeutic agent.

PMID- 9006782
TI  - Effects of toborinone on myocardial oxygen consumption in pacing-induced heart
      failure dogs.
AB  - The effects of a novel positive inotropic agent, toborinone ((+/-)-1-[3,4
      dimethoxy-benzylamino)-2-hydroxypropoxy]-2(1H)-quinolinone , CAS 128667-95-8, OPC
      18790, on myocardial oxygen consumption were examined in pacing-induced heart
      failure dogs. Ten dogs were ventricularly paced at 260 beats/min for 10 days to
      induce heart failure. Five of them were controls and the remaining five were
      given toborinone. Dogs were anesthetized with halothane, and cardiac functions,
      hemodynamics and myocardial oxygen consumption were measured. The peak of the
      first derivative of left ventricular pressure (LV dP/dtmax), cardiac output (CO)
      and mean blood pressure (mBP) were significantly decreased, and left ventricular
      end-diastolic pressure (LVEDP), mean right atrial pressure (mRAP), pulmonary
      capillary wedge pressure (PCWP) and mean pulmonary arterial pressure (mPAP) were
      also significantly increased after 10 days of rapid ventricular pacing.
      Toborinone (5 and 10 micrograms/kg/min) dose-dependently increased LV dP/dtmax,
      coronary blood flow (CBF) and CO and decreased LVEDP and systemic vascular
      resistance (SVR) without increasing myocardial oxygen consumption in the pacing
      induced heart failure dogs. These results suggest that toborinone may be useful
      for the management of chronic and congestive heart failure.

PMID- 9006784
TI  - Comparative toxicology of two enantiomers of the peripherally acting non-narcotic
      antitussive drug moguisteine.
AB  - Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl-1,3-t
      hiazolidine, CAS 119637-67-1), a new peripheral non-narcotic antitussive drug, is
      a racemate composed of an equimolar mixture of R(+) and S(-) enantiomers (BBR
      2221 and BBR 2222, respectively). Since in some cases the use of only one
      enantiomer instead of a racemate may increase the efficacy and/or the
      tolerability of a compound, moguisteine enantiomers were submitted to
      toxicological evaluation. Given in a single oral (gavage) or intraperitoneal
      administration to mice and rats, both moguisteine enantiomers show very low
      general toxicity. Administered by gavage to rats and dogs for four consecutive
      weeks, BBR 221 and BBR 2222 are tolerated at up to the dose of 240 mg/kg/day in
      both sexes with no appreciable toxic changes. Finally, the mutagenicity tests
      show that both enantiomers are devoid of any mutagenic potential both in vitro
      and in vivo. Considering the overall results of the toxicological studies and
      comparing them with the data obtained from the previously performed studies with
      the racemate moguisteine, it can be affirmed that no differences can be
      identified between the two enantiomers and the racemate moguisteine. These
      findings justify the development of moguisteine as a racemate since neither
      enantiomer should offer any advantage over the racemate.

PMID- 9006785
TI  - Effect of gallbladder contraction induced cholagogia on the pharmacokinetic
      profile of a sustained-release theophylline formulation.
AB  - Bile excretion might change the physiological milieu of the duodenum resulting in
      enhanced absorption of a drug due to increased solubilisation. This possible
      influence of bile salts following stimulation of gallbladder emptying via the
      release of cholecystokinin on the pharmacokinetics of a sustained-release
      theophylline (CAS 58-55-9) preparation (Bronchoretard) was evaluated in this
      study. An open, randomised 3-way cross-over study in 12 healthy, non-smoking
      volunteers was selected to prove or reject this hypothesis. All subjects received
      500 mg of the sustained-release theophylline formulation under two different
      cholagogia stimulating test conditions and under a fasting reference condition. A
      standard breakfast and i.m. application of cholecystokinin enabled modulation of
      bile flow; a moderate and extreme contraction of the gallbladder could be induced
      after a standard breakfast and after i.m. application of cholecystokinin,
      respectively. Following a standard breakfast, gallbladder volumes were
      approximately halved (50.6%) compared to the baseline volume after 79 min.
      Injection of 0.3 micrograms/kg body weight cholecystokinin resulted in quick and
      complete gallbladder evacuation (94.6%) 36 min after the application of this
      cholagogue stimulus. Gallbladder volumes remained approximately constant under
      fasting conditions. This manipulation of bile flow did not influence
      concentration/time profiles of the sustained-release theophylline preparation
      compared to the fasting condition. Even almost complete evacuation of the
      gallbladder after application of cholecystokinin did not modify
      concentration/time profiles of theophylline in a relevant way. An unintentional
      rapid release of theophylline could be excluded for this sustained-release
      formulation for all three treatments, as not a single case of dose-dumping was
      observed. Furthermore, in vitro dissolution investigations using surfactants are
      neither predictive of food effects nor bile influence on in vivo absorption at
      least for the sustained-release formulation tested.

PMID- 9006787
TI  - In vitro studies of some 2,4-disubstituted thiazolyl-aminoketones with anti
      inflammatory activity. Correlation with lipophilicity and structural
      characteristics.
AB  - A number of ring and chain substituted aminothiazole derivatives with strong anti
      inflammatory activity were studied for their antiproteolytic and oxygen radical
      scavenging properties. Their interactions with the stable free radical 1,1
      diphenyl-2-picrylhydrazyl was determined. Their inhibition of the soybean 12
      lipoxygenase and beta-glucuronidase enzymes was evaluated. They scavenged
      superoxide anion and inhibited proteolysis to a non appreciable extent, whereas
      no activity on beta-glucuronidase and lipoxygenase was found. Their reducing
      ability was found to be low. Good correlation was obtained between the anti
      inflammatory activity and clog P (theoretically calculated lipophilicity) and
      between anti-inflammatory activity and proteolytic inhibition. RM values were
      also determined.

PMID- 9006786
TI  - Effectiveness of the anticholinergic agent oxitropium bromide in elderly patients
      with bronchial asthma.
AB  - The short-term and long-term effects of the anticholinergic agent oxitropium
      bromide (CAS 30286-75-0, OTB) were studied in nine elderly patients with
      bronchial asthma (8 men and 1 women, age: 69.5 +/- 5.2 years, 3 atopic and 6 (not
      atopic cases). 2 h after inhalation of 0.8 mg of OTB, forced vital capacity (FVC)
      had increased from 2.28 +/- 0.22 1 to 2.87 +/- 0.27 1 (p < 0.01), forced
      expiratory volume in 1 s (FEV1) had increased from 1.22 +/- 0.14 to 1.57 +/- 0.16
      1 (p < 0.01), and respiratory resistance (Rrs) had decreased from 5.9 +/- 0.8
      cmH2O/l/s to 4.9 +/- 0.7 cmH2O/l/s (p < 0.05). The patients inhaled OTB (0.2 mg
      t.i.d.) for 6 weeks. Their peak expiratory flow rates, measured each morning and
      each evening, increased significantly during the first 2 weeks of administration,
      and the increase was sustained for the entire weeks (p < 0.05). Other pulmonary
      function tests were done before drug administration and again at the end of the 6
      weeks. By the end of the 6th week of OTB administration, FVC had increased from
      2.30 +/- 0.22 1 to 2.99 +/- 0.26 1 (p < 0.01), and FEV1 had increased from 1.25
      +/- 0.17 to 1.70 +/- 0.22 1 (p < 0.05). These data indicate that OTB can be
      useful in the treatment of elderly patients with bronchial asthma.

PMID- 9006788
TI  - Comparison of tissue and plasma levels of ibuprofen after oral and topical
      administration.
AB  - The penetration and absorption of ibuprofen (CAS 15687-27-1) from a topical gel
      and oral tablets were tested in an open study, performed in 17 patients with
      degenerative knee disorders requiring an operation. Patients administered the
      topical test preparation (ibugel, 3 x 375 mg ibuprofen daily) or the standard
      oral preparation (2 x 600 mg ibuprofen daily) for 3 days prior to the operation.
      Samples of blood, synovial fluid, muscle, fasciae and subcutis were obtained
      during the operation (15 h after the last administration) and analysed for
      ibuprofen content using a validated HPLC method. Different absorption profiles
      were observed for topical and oral administration. Oral administration led to
      higher concentrations in the plasma, synovial fluid and fasciae, while higher
      levels in the muscle and subcutis were found after topical administration. After
      topical application, the concentrations in the fasciae, muscle and subcutis were
      significantly higher than those in the blood plasma and synovial fluid (p <
      0.05). Very low levels of ibuprofen were observed in the subcutis after oral
      administration. This can be explained by the different pathways. This study
      demonstrated that concentrations of ibuprofen in the various biological samples
      were still within therapeutically effective levels 15 h after topical or oral
      administration. By use of an oral comparison group, it has been possible to show
      that the concentrations in times directly under the site of topical application
      lie in the same order of magnitude as those found after preoral treatment.
      Therapy of intra-articular inflammatory and degenerative joint diseases requires
      oral administration of non-steroidal anti-inflammatory drugs (NSAIDs). However,
      based on the results of this study, topical therapy with NSAIDs can be
      recommended for soft tissue rheumatism and periarticular insertion tendinopathia.

PMID- 9006789
TI  - Computer design and syntheses of antiulcer compounds. 2nd Communication: N
      substituted N'-[3-[3-(1-piperidinomethyl)phenoxy]propyl]ureas.
AB  - The in vitro and in vivo antiulcer effect of a series of N-substituted N'3-[3-(1
      piperidinomethyl)phenoxy]propyl]ureas was modeled by making use of the OASIS
      computer system for QSAR analysis. Various research schemes were employed
      depending on structural representation of chemicals under investigation, such as
      non-protonated (neutral), protonated at the piperidine and urea fragmental
      nitrogens, and with intramolecular hydrogen binding. According to the modeling
      results, it is likely a variety of structural forms of antagonist molecules to
      take part in the receptor interaction. The QSAR study showed that the larger the
      electron acceptor properties of the nitrogen and oxygen atoms of the urea
      fragment, the higher is in vitro and in vivo activity of the antagonists.

PMID- 9006790
TI  - Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer
      dyspepsia.
AB  - The efficacy and safety of the standardized herbal combination preparation of
      Enteroplant, consisting of peppermint oil (90 mg) and caraway (50 mg) in an
      enteric coated capsule, have been studied in a double-blind, placebo-controlled
      multicentre trial in patients with non-ulcer dyspepsia. A total of 45 patients
      were included in the trial after thorough physical and gastro-enterological
      examination. The primary outcome variables were the change in the intensity of
      pain and the global clinical impression (Clinical Global Impression [CGI], Item
      2), which were evaluated for 39 patients (test preparation: 19, placebo: 20).
      After four weeks of treatment both target parameters were significantly improved
      for the group of patients treated with the peppermint oil/caraway oil combination
      compared to the placebo group (p = 0.015 and 0.008, respectively). Before the
      start of treatment all patients in the test preparation group reported moderate
      to severe pain, while by the end of the study 63.2% of these patients were free
      of pain. The pain symptoms had improved in a total of 89.5% of the patients in
      the active treatment group. After 4 weeks the Clinical Global Impressions were
      improved for 94.5% of the patients treated with the peppermint oil/caraway oil
      combination. The trial medication was also superior to placebo with respect to
      pain frequency, medical prognosis, the severity of the disorder and the efficacy
      index (CGI, Items 1 and 3), which were adopted as secondary end-points for
      evaluation of efficacy. There were similarly favourable findings for the herbal
      combination, compared with placebo, with respect to the reduction of other
      gastrointestinal symptoms. The combination preparation was found to be
      excellently tolerated. There was a total of 7 adverse events (test preparation:
      4, placebo: 3), with a causal association with the treatment being ascribed in
      one case for the test preparation group and one case for the placebo group.

PMID- 9006791
TI  - Synthesis and antimicrobial activity of electron rich olefin derived cyclic
      ureas.
AB  - Seventeen cyclic ureas containing imidazolidine and benzimidazoline nuclei were
      synthesised by the reaction of electron-rich olefins with appropriate group 16
      elements. (O, S, Se, Te). The compounds synthesised were identified by 1H, 13C
      NMR, FT-IR and mass spectroscopic techniques and micro analysis. All compounds
      studied in this work were screened for their in vitro antimicrobial activity
      against standard strains: Enterococcus faecalis (ATCC 29212), Staphylococcus
      aureus (ATCC 29213), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa
      (ATCC 27853). Eight of the compounds were found effective to inhibit the growth
      of Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) at
      MIC values between 25-400 micrograms/ml. None of the compounds exhibit
      antimicrobial activity against gram-negative bacteria (Escherichia coli and
      Pseudomonas aeruginosa) at the concentrations studied (6.25-800 micrograms/ml).

PMID- 9006792
TI  - Inhibition of Trypanosoma cruzi epimastigotes in vitro by iron chelating agents.
AB  - The relative effectiveness of 20 iron chelating agents in suppressing the growth
      and multiplication of Trypanosoma cruzi epimastigotes has been examined in vitro.
      1,2-Dimethyl-3-hydroxypyrid-4-one (L1) and several of its newly synthesised N
      substituted analogs containing hydrophobic substituents were significantly more
      effective than deferoxamine, even though they possess only two donor sites for
      iron(III) while deferoxamine has six. Analogs with hydrophilic substituents were
      uniformly less active than L1 itself. Variations in effectiveness as the polarity
      of the compound is varied indicate that the ability to cross the cellular
      membrane is of critical importance in the determination of the in vitro
      trypanocidal activity of iron(III) chelating agents. A group of four tris(2
      aminoethyl)amine based tris-imines were also screened, all of which had poor
      activity (0-28% inhibition). Among the other iron(III) chelating agents which
      showed a relatively high level of activity at 50 and 100 micrograms/ml were
      salicylhydroxamic acid (70 and 73% inhibition) and hydroxyurea (42 and 52%
      inhibition). N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid and
      acetohydroxamic acid exhibited only slight activity at 50 and 100 micrograms/ml.
      The best of these iron(III) chelating agents were as effective against the
      epimastigote form at both 50 and 100 micrograms/ml (74-82% inhibition) as
      benznidazole (81% inhibition), the drug currently used in the clinic.

PMID- 9006793
TI  - Chemistry and biological activity of a tryptamine and beta-carboline series of
      bases.
AB  - Twenty-six derivatives of harmaline and tetrahydroharmine were prepared and
      characterized by UV, IR, MS, and NMR spectroscopy. They were tested for their
      antimicrobial, antiplatelet aggregation and cytotoxic activity. Their effect on
      central nervous system was also studied.

PMID- 9006794
TI  - Therapeutic effect of the quinolone prodrug prulifloxacin against experimental
      urinary tract infections in mice.
AB  - The in vitro antibacterial activity of prulifloxacin (CAS 123447-62-1, NM441), a
      new quinoline prodrug, against clinical isolates from urinary tract infections
      was investigated. In addition, it was compared with ofloxacin (CAS 82419-36-1),
      levofloxacin (CAS 100986-85-4), ciprofloxacin urinary tract infections in mice,
      as well as its pharmacokinetics. 1. The antibacterial activity of NM394 (6-fluoro
      1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2- a]quinoline-3-carboxylic
      acid), an active metabolite of prulifloxacin, against gram-positive clinical
      isolates was inferior to that of levofloxacin and tosufloxacin, and equal to that
      of ofloxacin and ciprofloxacin. Against gram-negative clinical isolates, the
      activity of NM394 was superior to that of the reference drugs. 2. The therapeutic
      effect of prulifloxacin on experimental urinary tract infection with Escherichia
      coli in mice was equal to that of tosufloxacin and ciprofloxacin and superior to
      that of ofloxacin and levofloxacin. Its therapeutic effect on Pseudomonas
      aeruginosa infection was equal to that of tosufloxacin and ciprofloxacin, and
      superior to that of ofloxacin. Against urinary tract infection with olfloxacin
      resistant Enterobacter cloacae, prulifloxacin was the most effective of all the
      drugs tested. 3. The maximal serum concentration of prulifloxacin was slightly
      higher than that of ciprofloxacin, and the area under the curve (AUC) for
      prulifloxacin was 1/4 that of ofloxacin, levofloxacin and tosufloxacin. The
      maximal concentration and AUC of prulifloxacin in lung and kidney were slightly
      higher than the corresponding values for ciprofloxacin but only 1/2 to 1/4 of the
      values for ofloxacin, levofloxacin and tosufloxacin. In conclusion, prulifloxacin
      (NM394) showed potent antibacterial activity against clinical isolates and potent
      therapeutic efficacy against experimental infection in spite of its lower AUCs
      compared with the reference drugs. These findings suggest that prulifloxacin may
      be a useful drug in the treatment of urinary tract infections.

PMID- 9006795
TI  - Stimulation of neutropoiesis by a special standardized mistletoe preparation
      after cyclophosphamide chemotherapy in mice.
AB  - Lektinol, is a special mistletoe preparation (SMP) with immunostimulatory
      activity, standardized with respect to bioactive mistletoe lectin, one of the
      most active components of mistletoe. In the present study, stimulation of
      leukopoiesis by SMP was investigated in mice after induction of myelosuppression
      by the cytostatic agent cyclophosphamide (CP). Under the experimental conditions
      described, CP induced severe leukopenia followed by a recovery phase where
      leukopoiesis was distinctly enhanced in mice treated additionally with SMP at
      daily intravenous doses in a range of 30 to 5000 microliters/kg body weight. This
      phenomenon was mainly due to a stimulation of granulopoiesis resulting in a
      stronger increase of metamyelocyte and mature neutrophil counts in the peripheral
      blood.

PMID- 9006797
TI  - Monitoring the glycosylation pattern of recombinant interferon-omega with high-pH
      anion-exchange chromatography and capillary electrophoresis.
AB  - The enzymatic glycosylation of certain asparagine residues in the protein
      structure has a profound influence on their physico-chemical properties. Many
      recombinant DNA derived glycoprotein pharmaceuticals for therapeutic use are
      glycosylated. Their oligosaccharides are important with regard to stability,
      solubility, in vivo activity and antigenicity. Sophisticated analytical methods
      that allow a high resolution of synthesized carbohydrate structures are therefore
      necessary to ensure a constant product quality. To elucidate the robustness of
      interferon-omega glycosylation regarding process modifications. Chinese Hamster
      Ovary (CHO)-cells expressing human interferon-omega were cultivated under
      different fermentation conditions. The most significant glycosylation alterations
      resulted from the varied parameters such as initial ammonia concentration in the
      production medium, cultivation mode (adherent versus suspended) or process time.
      These are detectable with HPAEC (high-pH anion-exchange chromatography)
      oligosaccharide mapping as well as with capillary electrophoresis.

PMID- 9006796
TI  - Effect of educational level, gender and age on the performance in a multi-user
      computerized psychometric test system for use in clinical pharmacological
      studies.
AB  - 197 native, drug-free healthy young volunteers performed psychometric tests on a
      single occasion, using a new multi-user computerized test system which consists
      of tests of simple reaction time, complex reaction time, vigilance,
      concentration, motor coordination, short-term memory (word pairs or figures) and
      abstract language-free reasoning (2 versions). Normality of distribution of all
      psychometric variables was checked. For the reasoning tests and the memory tests,
      internal consistency and parallel test reliability were determined. Cross
      correlations between the variables and factor analysis were done to evaluate
      whether different tests measure different brain functions. Multivariate variance
      analysis was carried out to test the effect of the independent factors school
      education, gender and age on the performance in the psychometric tests. Subjects
      with a lower school education level performed worse in the reasoning tests, the
      concentration test and the memory tests. Females were slower in the coordination
      test and made fewer correct solutions in the concentration test. Older subjects
      performed worse in the reasoning tests and had a longer working time in the
      memory tests than younger ones. The results show the necessity of psychometric
      screening of volunteers before recruitment for clinical pharmacological
      psychometric studies in order to reduce-individual variability.

PMID- 9006798
TI  - The L-arginine-nitric oxide pathway: role in atherosclerosis and therapeutic
      implications.

PMID- 9006799
TI  - Lp(a) concentrations are related to plasma lipid concentrations.
AB  - Lp(a) concentrations are controlled primarily by genetic variation at LPA, the
      locus encoding the unique protein apo(a). However, the high heritability is in
      part a consequence of nearly a 1000-fold range of Lp(a) concentrations found in
      healthy individuals. As determined by use of siblings genetically identical-by
      descent at the LPA locus, there is substantial within-genotype variation in Lp(a)
      concentrations (ranges averaged about 58% of mean values for 87 sibling groups).
      This within-genotype variation could affect risk of CVD for nearly 15% of
      individuals in a population. Furthermore, Lp(a) concentrations are significantly
      and independently correlated with two key indicators of lipoprotein metabolism,
      plasma cholesterol and triglyceride concentrations. Taken together, these data
      suggest that it is both possible and desirable to develop strategies for
      modifying Lp(a) concentrations.

PMID- 9006800
TI  - Effects of dietary vitamin C and E supplementation on the copper mediated
      oxidation of HDL and on HDL mediated cholesterol efflux.
AB  - Copper mediated oxidative modification of high density lipoprotein (HDL)
      diminishes its capacity to promote cholesterol efflux from cells in culture. In
      the present study, HDL was isolated from eight subjects before and after a 10 day
      administration of the antioxidant vitamins C and E. After incubation HDL (1.25 mg
      protein/ml) with 10 microM copper for 0-4 h or with 0-20 microM copper for 4 h,
      thiobarbituric acid reactive substances (TBARS) production was significantly
      decreased following vitamin administration suggesting that the vitamins decreased
      the susceptibility of HDL to oxidation. However, two other assays of lipoprotein
      oxidation, trinitrobenzene sulfonic acid reactivity and conjugated diene
      formation, did not show a consistent effect of vitamin administration. To study
      cholesterol efflux, J774 macrophages were labeled with 3H cholesterol (0.1
      microCi/ml, 50 micrograms/ml) and incubated with HDL or oxidized HDL (100
      micrograms protein/ml) for 24 h. HDL isolated before vitamins and oxidized in
      vitro was 39% less effective in mediating efflux compared to unmodified HDL,
      while HDL isolated after vitamins and oxidized was 22% less effective (before vs.
      after vitamins, P < 0.015). HDL oxidation determined by measuring TBARS
      production correlated with decreased cholesterol efflux (r = 0.37, P < 0.050).
      These data suggest that oxidation of HDL interferes with its role in reverse
      cholesterol transport and that antioxidant vitamins have a protective effect.

PMID- 9006801
TI  - Elevated lipoprotein(a) and increased incidence of restenosis after
      femoropopliteal PTA. Rationale for the higher risk of recurrence in females?
AB  - It has been shown that the incidence of recurrent stenosis following successful
      percutaneous transluminal coronary angioplasty (PTCA) is correlated with serum
      Lipoprotein(a) [Lp(a)] levels. The aim of the present study was to examine the
      influence of Lp(a) on restenosis after primary successful femoropopliteal PTA.
      One hundred and thirty nine consecutive patients with peripheral arterial
      occlusive disease (PAOD) and successful femoropopliteal PTA were studied. Follow
      up included clinical examination and non-invasive laboratory testing (pulse
      volume recordings, ankle-brachial arterial pressure measurement) in every patient
      before and after 1, 3, 6 and 12 months following intervention. Duplex sonography
      was performed 1 year after PTA. Suspicion of restenosis (> or = 50% diameter
      reduction) was verified by angiography. Lp(a) was determined using ELISA
      technique (mg/dl). Twelve months after successful PTA no restenosis was found in
      82 patients (59%: group A). The one-year recurrence rate of 41% (group B) was due
      to significant restenosis in 35 patients (25%) and reocclusion in 22 patients
      (16%). The corresponding mean values +/- S.E.M. for Lp(a) were as follows: group
      A, 28 +/- 5.3; group B 59 +/- 11 (P < 0.01). Women showed a higher frequency of
      recurrences (55%) versus men (30%, P < 0.01) also corresponding with a high Lp(a)
      level (51.8 +/- 8 versus 32.7 +/- 5; P < 0.05). Furthermore Lp(a) aggravated the
      well known increased risk for recurrence in multiple stenoses or occlusions of >
      or = 5 cm in length. There were no significant differences between groups A and B
      with respect to age, diabetes, hyperlipidaemia, obesity and cigarette smoking.
      The results support the view that Lp(a) is an independent risk factor for
      recurrence after PTA in the femoropopliteal area. It might also be a causal basis
      for the higher incidence of recurrences in female PAOD patients.

PMID- 9006803
TI  - Simvastatin increases plasma NO2- and NO3- levels in patients with
      hypercholesterolemia.
AB  - In this study, plasma NO2- and NO3- (NOx-) levels were studied after lowering
      cholesterol with simvastatin in 26 outpatients with hypercholesterolemia (male,
      9; female, 17; mean age, 59 +/- 12 years; cholesterol level > 220 mg/dl).
      Simvastatin (5 mg) was orally administered once daily, and blood samples were
      collected before, and after 4 and 12 weeks of treatment. Total, very-low-density
      lipoprotein (VLDL), and low-density lipoprotein (LDL) cholesterol were lowered
      (total, 254 +/- 44 mg/dl to 209 +/- 34 mg/dl; VLDL, 48 mg/dl [5-126 mg/dl] to 34
      mg/dl [10-67 mg/dl]; LDL, 171 +/- 41 mg/dl to 133 +/- 37 mg/dl), but high-density
      lipoprotein (HDL) cholesterol was elevated (33 +/- 9.5 mg/dl to 39 +/- 11 mg/dl)
      at 12 weeks after starting simvastatin. Although the effects of simvastatin on
      the lipid levels nearly reached their maximum levels at 4 weeks, NOx- was
      elevated in a linear fashion with simvastatin (before; 8 +/- 17 mumol/l, at 12
      weeks; 57 +/- 32 mumol/l). The % changes in the NOx- correlated directly with
      those in HDL-cholesterol at 12 weeks (P < 0.002) but not with other lipoprotein
      cholesterol fractions. These results suggest that simvastatin lowers cholesterol
      levels and elevates HDL while increasing the plasma NOx- levels.

PMID- 9006802
TI  - The association between free fatty acid concentrations and triglyceride-rich
      lipoproteins in the post-prandial state is altered by a common deletion
      polymorphism of the apo B signal peptide.
AB  - To investigate whether there were associations between the free fatty acid (FFA)
      response during a fat tolerance test and changes in concentrations of
      triglyceride-rich lipoproteins 57 healthy Caucasian men between 57 and 70 years
      of age underwent a fat tolerance test lasting 8 h. FFA concentrations initially
      decreased from 0.75 +/- 0.03 to 0.64 +/- 0.03 mmol/l at 2 h and thereafter
      increased to 1.2 +/- 0.04 mmol/l at 8 h. Maximum FFA concentration was the only
      significant determinant of 8 h triglyceride-rich lipoprotein (TGRLP)
      concentrations (pooled chylomicron and VLDL fractions d < 1.006) (TGRLP-TG r =
      0.33, P = 0.012; TGRLP apo B r = 0.37, P = 0.004; TGRLP cholesterol r = 0.38, P =
      0.004). The strength of the association between FFA and TGRLP was affected by the
      apo B signal peptide genotype. Only in individuals who were homozygous for the 27
      amino acid (SP27 or I) allele of the apo B signal peptide were there significant
      associations between maximum FFA concentration quartile and 8 h TGRLP
      concentration (P value for linear trend = 0.025). In this genotype group there
      were lower HDL cholesterol concentrations (1.16 mmol/l compared to 1.38 mmol/l in
      subjects either heterozygous or homozygous for the SP24 [D] allele; P = 0.005)
      and there was a trend toward increased 8 h TGRLP concentrations. We propose that
      the association between post-prandial FFA concentrations and post-prandial TGRLP
      concentrations in individuals who are homozygous for the SP27 allele may be
      linked to the increased prevalence of ischemic heart disease (IHD) in this
      genotypic group.

PMID- 9006804
TI  - Effect of glucose, insulin, and insulin-like growth factor-I on glucose transport
      activity in cultured rat vascular smooth muscle cells.
AB  - Glucose transport activity in cultured rat vascular smooth muscle cells (VSMCs)
      was examined under various concentrations of D-glucose, insulin, and insulin-like
      growth factor-I (IGF-I). Confluent cultures of VSMCs were incubated with serum
      free medium containing 0-25 mmol/l of D-glucose for 24-49 h. The basal rate of 2
      deoxyglucose uptake was reduced in association with increasing concentrations of
      D-glucose. Uptake of 2-deoxyglucose into the cells was linear between 0 and 15
      min of incubation regardless of the glucose concentration. The uptake was
      inhibited by the addition of 10 mumol/l cytochalasin B or 100 mmol/l D-glucose
      indicating that the effects were mediated by specific integral glucose carriers.
      The effect of D-glucose was time-dependent and reversible. Insulin increased the
      uptake of 2-deoxyglucose in a dose-dependent manner, and its effect was dependent
      on the preincubation dose of D-glucose. Insulin-stimulated uptake was lower in
      the cells pre-exposed to 25 mmol/l D-glucose than in the cells pre-exposed to
      concentrations of D-glucose below 5.5 mmol/l. After a long-term incubation with
      insulin, the insulin-stimulated glucose transport was inhibited. Recovery of
      glucose transport activity was assessed by incubating cells with D-glucose for 24
      48 h to induce desensitization. After a 24 h glucose conditioning, the uptake of
      2-deoxyglucose was lower in the cells preincubated with 25 mmol/l glucose than in
      the cells preincubated with 5.5 mmol/l glucose. The effect of the glucose
      conditioning was reversible and dependent on the preincubation dose of D-glucose.
      IGF-I was a more potent stimulator of glucose transport than insulin. Wortmannin,
      an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), inhibited the uptake
      of glucose stimulated by insulin or IGF-I in a dose-dependent manner. Our results
      suggest that D-glucose regulates its own uptake independently of insulin and
      modulates the ability of insulin to induce insulin resistance in the cultured rat
      VSMCs. Glucose attenuated the effect of insulin, and led to a progressive
      decrease in the activity of the glucose transport effector system. Activation of
      wortmannin-sensitive PI3-kinase may be involved in the signaling pathways of the
      insulin- and IGF-I-stimulated glucose uptake in VSMCs. This mechanism of insulin
      resistance may be relevant to the formation of cellular defects in the vascular
      wall in patients with diabetes mellitus.

PMID- 9006805
TI  - Ischemia-induced alteration of myocardial Na(+)-K(+)-ATPase activity and ouabain
      binding sites in hypercholesterolemic rabbits.
AB  - The purpose of this study was to explore the effect of ischemia on the Na(+)-K(+)
      ATPase activity and ouabain receptor of the myocardial sarcolemma in
      hypercholesterolemic rabbits. Male New Zealand white rabbits were fed with either
      standard chow or standard chow supplemented with 0.5% (w/w) cholesterol and 10%
      (w/w) coconut oil. After an 8 week feeding period, the rabbits underwent a
      thoracotomy and myocardial ischemia was induced by occlusion of the coronary
      artery. Myocardial samples from the ischemic and non-ischemic regions of the left
      ventricle of control and cholesterol-fed rabbits were taken for study. The
      cholesterol-fed group showed a decrease in both Na(+)-K(+)-ATPase activity and
      [3H]ouabain binding sites as compared to the control group. Ischemia caused a
      reduction in both Na(+)-K(+)-ATPase activity [3H]ouabain bindings sites in both
      control and cholesterol-fed rabbits. The combination of ischemia and
      hypercholesterolemia produced an additive effect, with a further decrease in both
      Na(+)-K(+)-ATPase activity and [3H]ouabain binding sites. Neither the activity of
      Mg+(+)-ATPase nor the binding affinity for [3H]ouabain was affected by either
      hypercholesterolemia or ischemia. These findings indicate that
      hypercholesterolemia may exaggerate certain aspects of functional deterioration
      arising during myocardial ischemia.

PMID- 9006807
TI  - Influence of apolipoprotein E polymorphism on the tracking of childhood levels of
      serum lipids and apolipoproteins over a 6-year period. The Bogalusa Heart Study.
AB  - The influence of apolipoprotein (apo) E polymorphism on the tracking of serum
      lipoprotein variables over a 6-year follow-up period was examined in 442
      individuals aged 5-15 years at baseline. The apo E phenotype-specific differences
      in total cholesterol and low-density lipoprotein (LDL) cholesterol levels
      persisted in the study cohort at baseline and follow-up examinations. However,
      the correlations of baseline versus follow-up levels of total cholesterol and LDL
      cholesterol varied according to the apo E phenotype group, with the apo E2 group,
      carrying E2/2 and E3/2 phenotypes, showing highest correlation for these
      variables (r = 0.73 - 0.74) and the apo E4 carrying E3/4 and E4/4 phenotypes the
      lowest (r = 0.48 - 0.59). The tracking correlation for LDL cholesterol in the apo
      E2 group was different form that of the other phenotype groups (P < 0.05). In
      terms of persistence in ranks over time, of the individuals who were in the
      highest quartile of LDL cholesterol at baseline none of those in the apo E2
      group, 63% of those in the apo E3 group carrying E3/3 phenotype, and 60% of those
      in the apo E4 group maintained this high rank at follow-up; corresponding values
      for persistence in ranking at the lowest quartile over time were 82% for the apo
      E2 group, 57% for the apo E3 group, and 33% for the apo E4 group. Further, in a
      multiple regression model, apo E phenotype was retained as a predictor variable
      only in the case of LDL cholesterol. Thus, apo E polymorphism influences not only
      the level of LDL cholesterol in childhood, but also its tracking at least over a
      6-year period.

PMID- 9006806
TI  - The serum cholesterol ester fatty acid composition but not the serum
      concentration of alpha tocopherol predicts the development of myocardial
      infarction in 50-year-old men: 19 years follow-up.
AB  - A low serum tocopherol concentration and a low proportion of linoleic acid in
      plasma cholesterol esters have been reported to be associated with coronary heart
      disease. This study was undertaken to evaluate the predictive importance of the
      serum cholesterol ester fatty acid composition and serum tocopherol concentration
      in addition to established risk factors for myocardial infarction. The study
      comprised 2322 fifty-year-old men who participated in a health survey in 1970
      1973 regarding risk factors for coronary heart disease. The proportions of
      myristic, palmitic, palmitoleic, and dihomogammalinolenic acid were significantly
      higher in 1970-1973 in subjects who suffered myocardial infarction during the
      following 19 years, while the proportion of linoleic acid was lower, than in
      those who remained healthy. Serum tocopherol did not differ significantly between
      the groups. LDL/HDL ratio, systolic blood pressure, and arachidonic
      acid/dihomogammalinolenic acid ratio were significant independent discriminators
      between cases and controls in a stepwise logistic regression analysis. This study
      suggests that middle-aged men who later develop a myocardial infarction are
      characterized not only by conventional risk factors but also by an altered fatty
      acid composition of serum cholesterol esters, with a low arachidonic to
      dihomogammalinolenic acid ratio, indicating reduced delta 5 desaturase activity.
      This may imply that changes in the quality of dietary fat intake, or an altered
      capacity to metabolize fatty acids in the body, could precede the development of
      coronary heart disease.

PMID- 9006808
TI  - Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein
      cholesterol esterification and transfer rates to lighter density lipoproteins in
      the fasting state and after a test meal are similar in Type II diabetics and
      normal controls.
AB  - Rates of ester formation from [3H]cholesterol and of [3H]cholesteryl ester
      transfer from the HDL-containing plasma fraction to lipoproteins of lighter
      densities (apo B-containing LP) and plasma cholesteryl ester transfer protein
      concentration (CETP) were measured in normotriglyceridemic Type II diabetics (n =
      11) and normal controls (n = 10) both in the fasting state and 4 h after a
      standard milk-shake test meal (50g of fat/m of body surface). The percent of
      [3H]cholesteryl ester synthesis was measured in a plasma [3H]cholesterol-HDL
      containing preparation incubated for 30 min and the [3H]cholesteryl ester
      transfer was measured upon precipitation of apo B-containing lipoproteins with
      dextran sulphate/MgCl2 following a 2 h period of plasma incubation with
      [3H]cholesteryl ester-HDL. The test meal significantly increased the plasma
      triglyceride concentration and to a similar extent in diabetics and in normal
      controls. Both a HDL-[3H]cholesteryl ester synthesis and transfer rates were
      equally stimulated in diabetics and in controls. When data were expressed by the
      concentration of plasma triglycerides, cholesteryl ester formation and transfer
      rates were similar in the alimentary and fasting periods, and when expressed per
      apo B concentration, cholesteryl ester transfer rates rose during the alimentary
      period in both diabetics and controls indicating that there was a net gain of
      cholesteryl ester per apo B lipoprotein. Plasma CETP mass, and neutral lipid
      transfer activity were similar in diabetics and normal controls demonstrating
      that the reverse transport of cholesterol through the apo B lipoprotein pathway
      is not altered in normotriglyceridemic Type II diabetics.

PMID- 9006809
TI  - Opposite effects of bezafibrate and gemfibrozil in both normal and
      hypertriglyceridemic rats.
AB  - Chow and sucrose-fed rats were used as animal models to study the dose-responses
      of bezafibrate and gemfibrozil in normolipidemic and hypertriglyceridemic states,
      respectively. Although both drugs lowered plasma triglycerides (TG) to about the
      same extent in chow-fed rats, gemfibrozil lowered liver TG as well as plasma
      total and LDL-cholesterol (LDL-C), but elevated HDL-cholesterol (HDL-C) and
      plasma apo E concentrations. Bezafibrate produced opposite effects, namely,
      decreased HDL-C, apo E and liver TG, and tended to increase LDL-C. TG lowering
      for both drugs in chow-fed rats was not due to changes in TG secretion
      (production) in normal rats but was associated with enhanced LPL activity. In
      hypertriglyceridemic rats both drugs modestly reduced TG secretion rates about
      40% at a dose producing maximal TG lowering, but again, gemfibrozil elevated and
      bezafibrate lowered HDL-C and apo E. Unlike gemfibrozil, bezafibrate induced the
      appearance of LDL-C in hypertriglyceridemic rats which was not detected in
      control animals, and also tended to increase rather than decrease plasma apo B
      levels. Finally, changes in liver TG concentration (mg/g) in hypertriglyceridemic
      rats were opposite for these drugs, resulting in significant drug-related
      differences in liver TG content (mg/organ). From these data we postulate that,
      although similar with regard to TG lowering activity and mechanisms thereof,
      gemfibrozil and bezafibrate produce fundamentally different effects on LDL, HDL
      and apolipoprotein metabolism (apo B and apo E) in rats which may relate to
      potential differential effects on reverse cholesterol transport and
      atherogenesis.

PMID- 9006810
TI  - Carotid artery and left ventricular structural relationship in asymptomatic men
      at risk for cardiovascular disease.
AB  - To determine whether a relationship between echographically assessed carotid
      artery and left ventricular (LV) structures existed in asymptomatic men at risk
      for cardiovascular disease, we evaluated carotid and LV parameters in 69 subjects
      (23-62 years) without LV hypertrophy. The right common carotid far wall intima
      media thickness (IMT) was measured using an automated technique and the cross
      sectional intima-media complex area (IMC-CSA) was calculated, assuming a circular
      profile of carotid wall layers, as (IMC-CSA = pi x IMT x (IMT + D)), D being the
      lumen diameter. LV mass was evaluated using the M-mode echocardiography. Among
      study subjects 30% were hypertensive, 67% hypercholesterolemic, 21% current
      smokers and 52% had a positive smoking history. In the study population LV mass
      correlated both with IMT (r = 0.54, P < 0.001) and IMC-CSA (r = 0.62, P < 0.001).
      In multivariate analysis LV mass was associated with IMC-CSA (P < 0.001), body
      mass index (P < 0.01), lifelong smoking dose (P < 0.01) and systolic blood
      pressure (P < 0.05), r2 = 0.58, P < 0.001. Therefore, IMC-CSA may be a clinically
      relevant independent indicator of LV mass even within its normal ranges.

PMID- 9006811
TI  - Effects of regular and extended-release gemfibrozil on plasma lipoproteins and
      apolipoproteins in hypercholesterolemic patients with decreased HDL cholesterol
      levels.
AB  - We have studied, in a prospective blinded fashion, the effects of regular and
      extended-release gemfibrozil on plasma lipoprotein and apolipoprotein (apo)
      levels in hypercholesterolemic subjects with decreased high density lipoprotein
      (HDL) cholesterol (C) levels. Study participants were men and women 19 to 80
      years of age with baseline plasma low density lipoprotein (LDL) C levels > or =
      4.5 mmol/l (175 mg/dl), HDL-C levels < or = 1.2 mmol/l (45 mg/dl), and
      triglyceride levels < or = 3.4 mmol/L (300 mg/dl). All subjects were stabilized
      on a diet for eight weeks prior to entry into two different protocols. In the
      first protocol 229 subjects were randomized to placebo or extended-release
      gemfibrozil (1200 mg/day) for 3 months (placebo trial). In the second protocol
      655 subjects were randomized to regular or extended-release gemfibrozil (1200
      mg/day) for 6 months (equivalency trial). Changes in lipids and apos were
      stratified by baseline HDL-C levels (< 0.9 mmol/l, and 0.9-12.2 mmol/l). In both
      studies, treatment with gemfibrozil, either regular or extended-release, was
      associated with significant (P < 0.05) decreases in plasma very low density
      lipoprotein (VLDL) C and triglyceride levels of 42-45% and 33-37%, respectively,
      in subjects with HDL-C level < 0.9 mmol/l, and of 38-47% and 32-39%,
      respectively, in patients with HDL-C levels of 0.9-1.2 mmol/l. Modest reductions
      from baseline in directly measured LDL-C levels were observed in both groups (3
      6% and 8-9%, respectively). These reductions were less than those observed for
      calculated LDL-C (7-10% and 11%, respectively). For apo B, reductions were 11-14%
      and 16-17% in the two groups. HDL-C, apo A-I, and apo A-II levels increased by 15
      16%, 5-6%, and 21-25%, respectively, in patients with HDL-C < 0.9 mmol/l, and by
      6-7%, 2-3%, and 19-22%, respectively, in patients with HDL-C of 0.9-1.2 mmol/l.
      These differences in HDL-C levels reached statistical significance in the
      equivalency trial (P < 0.0001) and were independent of baseline triglyceride
      levels. Our data indicate that gemfibrozil, either regular or extended-release,
      is highly effective in lowering plasma triglyceride levels and increases HDL-C
      levels by approximately 15% in hypercholesterolemic patients with low HDL-C
      levels (< 0.9 mmol/l). Moreover, this agent lowers VLDL-C somewhat more than
      triglyceride, resulting in an underestimation of calculated VLDL-C reductions and
      in an overestimation of calculated LDL-C reductions. This agent also raises apo A
      II levels much more than apo A-I levels.

PMID- 9006812
TI  - The effects of renin-angiotensin system inhibition on aortic cholesterol content
      in cholesterol-fed rabbits.
AB  - To investigate how the renin-angiotensin system (RAS) might be involved in
      cholesterol-induced atherosclerosis, we studied the effects of a nonsulhydryl
      angiotensin converting enzyme (ACE) inhibitor, enalapril, and an angiotensin II
      receptor antagonist, E-4177, in cholesterol fed rabbits. Japanese white rabbits
      were randomly divided into four groups with the following dietary regimens: group
      A (n = 8) received a standard diet; group B (n = 8) had a 0.5% cholesterol diet;
      group C (n = 8) had a 0.5% cholesterol diet plus enalapril (10 mg/kg/day, p.o.);
      group D (n = 8) received a 0.5% cholesterol diet plus E-4177 (20 mg/kg/day, p.o.)
      and were fed these diets for 5 weeks. Enalapril or E-4177 had no significant
      effect on either the total plasma or the high density lipoprotein (HDL)
      cholesterol concentrations. However, the aortic cholesterol content in groups C
      and D was equally significantly less than that in group B. The plasma and aortic
      ACE activities were significantly reduced only in group C compared with those in
      the other groups. The aortic ACE mRNA and AT1 mRNA levels were assessed by a
      reverse transcription polymerase chain reaction (RT-PCR). The aortic ACE mRNA
      level was only significantly less in group C than in any of the other groups. The
      aortic AT1 mRNA level increased significantly in group B compared with that in
      group A and was significantly and equally reduced in both groups C and D compared
      with that in group B. These data indicate that angiotensin II rather than ACE may
      therefore be related to aortic cholesterol content. It follows therefore that the
      inhibition of angiotensin II by either ACE inhibitor or angiotensin II (type 1)
      receptor antagonist may play a role in prevention of atherosclerosis.

PMID- 9006814
TI  - Functional abnormalities of the aorta.

PMID- 9006813
TI  - Interstitial fluid apolipoprotein A-II: an association with the occurrence of
      myocardial infarction.
AB  - A sample of male patients aged 25-64 years, survivors of myocardial infarction
      (MI) taken from the Lille MONICA register, and age-matched control subjects from
      the general population were recruited in Lille and its surroundings in the North
      of France. Diabetics and subjects taking hypolipidemic drugs were excluded from
      the analysis, so that 73 MI and 144 control subjects were included. Lipids,
      apolipoprotein (apo) A-I, apo A-II, apo A-IV and apo B, and apo A-I-containing
      particles such as lipoproteins containing both apo A-I and apo A-II (LpA-I:A-II)
      and those containing apo A-I but not apo A-II (LpA-I) were measured in
      interstitial fluid by applying mild suction, and in plasma. Univariate analysis
      showed that plasma triglycerides, very low density lipoprotein (VLDL)-cholesterol
      and apo B were significantly higher, while high density lipoprotein (HDL)
      cholesterol, apo A-I, LpA-I and LpA-I:A-II were lower in MI survivors compared to
      controls after adjustment for age, body mass index (BMI), alcohol and tobacco
      consumption. In interstitial fluid, cholesterol and apo A-II were higher in MI
      than in controls before adjustment for covariates. However, after adjustment,
      triglycerides became significant while cholesterol and apo A-II remained
      significantly higher in MI, at 43.8 and 7.5 mg/dl, respectively, than in control
      subjects, at 38.6 and 5.9 mg/dl, respectively. Taking into account only the
      plasma parameters, the multivariate analysis reveals that triglycerides and apo A
      I appear to be independent factors indicative of the presence of a MI. When
      plasma and interstitial fluid parameters were taken together in the multivariate
      analysis, the measurement of apo A-II in interstitial fluid increased the level
      of prediction of MI over the information provided by the plasma parameters. These
      data raise the possibility that interstitial fluid apo A-II levels may be
      associated with the occurrence of MI.

PMID- 9006815
TI  - Treatment of preterm cervical dilatation with glyceryl trinitrate, a nitric oxide
      donor.
AB  - We report an observational study on the use of transdermal glyceryl trinitrate as
      a treatment to delay delivery of women presenting in pregnancy with dilatation of
      the cervix. Ten women found to have cervical dilatation more than 2 cm (range 2
      to 8 cm) at gestations between 16 and 32 weeks were studied. These women were
      treated with 50 mg glyceryl trinitrate patches. The mean prolongation of
      gestation from the time of admission was 46.2 days (range 1 to 130 days). There
      was 1 stillbirth in a 22.6-week fetus and 1 neonatal death secondary to
      prematurity. Vaginal delivery occurred in all but 3 cases. All babies were of
      size appropriate for gestational age at delivery. The only reported maternal side
      effect was headache. No adverse fetal effects were noted. We conclude that
      glyceryl trinitrate may provide an effective and safe method of tocolysis, well
      suited for long-term use. The purpose of reporting this study is to highlight the
      mounting accumulation of data on glyceryl trinitrate and reinforce the need to
      evaluate its use in randomized controlled trials.

PMID- 9006816
TI  - First trimester aneuploidy screening using nuchal translucency, free beta human
      chorionic gonadotrophin and maternal age.
AB  - Screening for aneuploidy using maternal age has a low detection rate and high
      false positive rate. Second trimester maternal serum screening increases trisomy
      21 detection and decreases the false positive rate. First trimester screening
      would enable definitive diagnosis with chorionic villus sampling, and simple
      surgical termination of affected pregnancies would still be an option. Nuchal
      translucency (NT), free beta human chorionic gonadotrophin (f beta HCG) and
      maternal age were assessed in 302 patients before chorionic villus sampling. NT
      positively and f beta HCG negatively correlated with gestation, but neither
      correlated with maternal age nor with each other. Both NT and f beta HCG were
      increased in trisomy 21. NT was increased and f beta HCG was decreased in trisomy
      18. Multivariate discriminant analysis enabled 87.5% detection of trisomy 21 in
      this high-risk population, for a 14% false positive rate. In a simulated normal
      population, using a risk cut-off of 1 in 250, 71% detection was achieved for a 7%
      false positive rate. The combination of NT, f beta HCG and maternal age is a
      simple, readily available and viable first trimester screening strategy.

PMID- 9006817
TI  - The impact of antenatal screening for Down syndrome in Western Australia: 1980
      1994.
AB  - Since the early 1970s, women in Western Australia have been screened for fetal
      Down syndrome risk on the basis of maternal age. Women 35 years of age or more at
      delivery, were offered fetal karyotyping with genetic diagnostic testing via
      amniocentesis or chorionic villus sampling. An increase in the prevalence of Down
      syndrome of 3.9% per year (95% confidence interval: 1.8-6.0%) was observed
      between 1980 and 1994, almost all of which was accounted for by increased
      maternal age. In 1991, a maternal serum screening (MSS) programme for Down
      syndrome was first implemented in Western Australia and has since evolved in 6
      separate laboratories providing Down risk assessment in 1994. The gradual
      introduction of MSS programmes had little discernible impact until 1994, when 38%
      of Down syndrome fetuses were ascertained as a result of increased-risk MSS tests
      and the birth prevalence of Down syndrome decreased significantly. In this
      report, we review antenatal screening programmes and their impact on the birth
      prevalence of Down syndrome in Western Australia.

PMID- 9006818
TI  - Booking ultrasound examinations performed by obstetric senior house officers-
      time to reevaluate?
AB  - We evaluated the proficiency of obstetrics senior house officers, not formally
      trained in ultrasonography, in assessing fetal viability, the number of fetuses
      and gestational age. Of 366 women who had an ultrasound examination at the first
      antenatal visit, 7 (2.1%) had nonviable pregnancies and 7 pairs of twins were
      correctly identified. Of these women, 329 had a detailed anomaly scan at 18-20
      weeks. No anomalies were detected at either scan. Of the booking scans performed
      by the senior house officers, 89.4% correctly assessed the gestational age of the
      pregnancy when compared to the anomaly scan (+/- 1 week). One in 10 of the scans
      performed by the senior house officers was inaccurate. This is important
      particularly when being used for risk assessment in serum screening for Down
      syndrome. At present the early ultrasound scan should be performed by more
      formally trained personnel.

PMID- 9006819
TI  - Prevention of infection in obstetrical and gynaecological ultrasound practice.

PMID- 9006820
TI  - Visual effect of partogram designs on the management and outcome of labour.
AB  - A prospective study of 3 partogram designs was performed in 990 women in labour
      with singleton pregnancy. Partogram A, B and C showed a progressively flatter
      steepness of the curve of labour progression. Oxytocin was administered in 35.1%
      of partogram-A users, 45.9% of partogram-B users (p = 0.001) and 44.1% of
      partogram-C users (p = 0.035). Significantly fewer patients among the partogram-A
      users (10.2%) were administered oxytocin too early compared to 18.6% of partogram
      B users and 20.5% of partogram-C users. Of those with spontaneous onset of
      labour, a significantly smaller total dose of oxytocin was administered to the
      partogram-A users compared to the other 2 groups. Ominous
      electrocardiotocographic fetal heart patterns were detected less frequently
      during the first stage of labour in partogram A users (0.4%) compare to partogram
      B users (1.1%) and partogram-C users (3.0%). Significantly fewer infants born to
      partogram-A users had depressed Apgar scores at 1 and 5 minutes. Partograms
      displaying a flat graph, compared to a steep graph, were more often considered to
      have a slow progress of labour. Adoption of partograms showing a steep graph of
      progress of cervical dilatation is recommended.

PMID- 9006821
TI  - Risk factors for meconium-aspiration syndrome.
AB  - The aim of this retrospective study was to identify risk factors for meconium
      aspiration syndrome, and to identify antenatal and intrapartum risk factors which
      might be preventable. We analyzed maternal and neonatal records of the 210
      infants who had meconium-stained liquor and who also developed respiratory
      distress necessitating admission to the Special Care of Intensive Care Baby Units
      at National Women's Hospital, Auckland in 1992. Meconium-aspiration syndrome
      occurred in 6.6% of meconium exposed babies and in 1.3% of total births. Severe
      meconium-aspiration syndrome developed in 18 infants, moderate in 48, mild in 60
      respiratory distress in 84. An association was found between meconium aspiration
      syndrome and primiparity (p = 0.001) and Pacific Island ethnicity (p = 0.0002).
      An association was also found between the severity of meconium and low umbilical
      artery pH (p = 0.0002). Thick meconium and an abnormal cardiotocograph were more
      common in severe meconium-aspiration syndrome. All deaths and long-term morbidity
      occurred in babies with abnormal cardiotocographs or in unmonitored infants.
      Preventable antenatal and intrapartum factors were not identified in this study.

PMID- 9006822
TI  - Amnioinfusion for the prevention of meconium aspiration during labour.
AB  - The aim of this observational study is to review the outcome of prophylactic
      intrapartum amnioinfusion (AI) in pregnancies complicated by moderate to thick
      meconium-stained liquor (MSL). The labour and neonatal outcome of all 298 AIs
      performed over a 3-year period were compared to a matched-control group of
      patients whose labour was complicated by moderate or thick MSL but without AI.
      The incidence of moderate or thick meconium below the vocal cords of the neonate
      were significantly lower in the AI group (6.4% and 3.4%) compared with the
      control group (15.4% and 6.7%). The incidence of meconium aspiration syndrome in
      the AI group was half (1.7%) that of the control group (3.7%), although the
      difference did not reach statistical significance. There was a significant higher
      incidence of cardiotocographic abnormalities in the AI group (30.5% versus
      14.7%), with higher incidences of Caesarean section and operative vaginal
      deliveries. The reduction in the incidence and thickness of meconium after AI was
      not accompanied by any statistically significant reduction in adverse fetal
      outcomes such as low Apgar scores, cord pH values, admissions to and duration of
      admission to the neonatal unit, or the incidence of meconium-aspiration syndrome.

PMID- 9006823
TI  - Important components of antenatal care: midwives' and obstetricians views.
AB  - This study sought the views of midwives and obstetricians about what they
      considered to be important aspects of routine antenatal care. Midwives and
      obstetricians were randomly selected from the NSW membership lists of the
      Australian College of Midwives and the The Royal Australian College of
      Obstetricians and Gynaecologists, respectively. Seventy-eight percent of midwives
      (n = 196) and 52% of obstetricians (n = 114) completed a questionnaire which
      itemised components of routine care derived from the National Health and Medical
      Research Council's Guidelines for Antenatal Care. Participants were asked to rate
      each of the 77 components on a 4-point scale as either: very important; desirable
      but not essential; not necessary; or, don't know. Twenty-four (31%) of the
      components were rated as very important by at least 90% of midwives and 19 (22%)
      were rated as very important by at least 90% of obstetricians. 'Recording details
      of previous pregnancy complications' was the component most commonly rated as
      being very important by both groups. On 37 (48%) of the components there was a
      significant difference between midwives and obstetricians in terms of whether or
      not they rated the component as very important (p < 0.01). There were
      considerable differences between midwives' and obstetricians' views about the
      important components of routine antenatal care and a substantial proportion of
      both groups did not consider many of the components listed in the guidelines to
      be essential in routine care. The findings suggest that a revision of the current
      antenatal care guidelines is necessary.

PMID- 9006824
TI  - Induction of labour for trial of vaginal birth after caesarean section in a
      remote district hospital.
AB  - In a retrospective review of 79 women with 1 or more previous Caesarean section,
      33 (41.8%) women agreed to a trial of vaginal birth. Twenty nine women had labour
      induced and 26 (89.7%) of them had a successful vaginal delivery. Four women
      laboured spontaneously and 1 of them needed an emergency Caesarean section for
      failure to progress. The overall vaginal delivery rate for women selected to
      undergo a trial of vaginal birth after Caesarean was 87.9%. The overall emergency
      Caesarean section rate was 4 of 33 (12.1%). During the study period the Caesarean
      section rate for the hospital fell from 32.2% to 11%. This study suggests that
      induction of labour in women with a previous Caesarean section is very successful
      in achieving vaginal delivery and has a role to play in remote and rural
      hospitals.

PMID- 9006825
TI  - Is 'herbal health tonic' safe in pregnancy; fetal alcohol syndrome revisited.
AB  - So called 'Herbal Health Tonics' are freely available in the market. This has
      been promoted by the manufacturers for the following symptoms: poor appetite,
      gastroenteric weakness, poor blood circulation, chills, fatigue, weak
      constitution and weakness after disease. We report a case of suspected fetal
      alcohol syndrome (FAS). A baby boy of 3,700 g born to a 29-year-old Chinese
      mother at 41 weeks' gestation was found to have features consistent with FAS. On
      follow up at 3 years of age, both motor and mental milestones as well as speech
      and language were delayed suggesting the possibility of FAS. There was a history
      of maternal ingestion of 'Herbal Health Tonic' (which contained 14% alcohol)
      daily for the first 2 months of the antenatal period. She denied exposure to
      alcohol or any other drugs. The authors would like to highlight the risk of such
      'Herbal Health Tonics' in pregnancy and their probable deleterious effects on the
      growing fetus. We feel that it is extremely important to look into the
      traditional practices among pregnant women in Singapore and in other parts of the
      world where there are similar practices, otherwise more cases like these could
      occur in future.

PMID- 9006826
TI  - Clinical implications and management strategies when depression occurs during
      pregnancy.

PMID- 9006828
TI  - What's in a name--is the pregnant woman a mother? Is the fetus a baby?

PMID- 9006827
TI  - Maternal country of origin and infant birthplace: implications for birth-weight.
AB  - This study investigated the effect of mother's country of origin and baby's
      birthplace on infant birth-weight. The mean birth-weights of full-term babies
      born of well immigrant women from 5 countries were compared with those of women
      of Anglo-Australian origin confined at the same hospital. Data were collected
      from medical records at Canterbury hospital for 1,274 women confined between 1989
      and 1992 and 2,524 of their babies. Multiple regression analysis showed that
      infants born in Australia to women from Vietnam and Korea were significantly
      heavier than infants born to these women in their country of origin. Babies born
      to women from Vietnam were significantly lighter than babies born to Anglo
      Australian controls.

PMID- 9006829
TI  - Mild cervical atypia: a management dilemma.
AB  - This study examined 117 patients with mild cervical atypia or atypical squamous
      cells of uncertain significance; it was found that 25% had histologically proven
      CIN lesions by colposcopically-directed punch biopsy or cone biopsy. 18% were
      found to have at least CIN 2 lesions and there was 1 case of invasive cancer.
      These data strongly support the recommendation of early colposcopic referral in
      patients with mild cervical atypia.

PMID- 9006830
TI  - An audit of hysterectomies in young women at the Queen Victoria Hospital, 1984
      1994.
AB  - A retrospective audit of hysterectomies in young women (age 30 years and under)
      was conducted. Forty-one hysterectomies, representing 4% of all hysterectomies at
      the hospital, were performed in women of this age group. The main clinical
      indications were abnormal uterine bleeding (44%), pelvic pain (20%) and
      endometriosis (15%). None were performed for invasive malignant conditions. Most
      women had some prior therapy for their symptoms. Thirty-seven of the operations
      were total abdominal hysterectomies and 4 women had a unilateral oophorectomy.
      Complications were found in 17 women. Causal pathology, though not always what
      was predicted clinically or on the basis of operative findings, was identified.
      Further studies would be worthwhile to document the experience from other
      institutions and to provide long-term follow-up.

PMID- 9006831
TI  - How do New Zealand gynaecologists treat menorrhagia?
AB  - The objectives of this study were to establish the criteria and technique that
      New Zealand gynaecologists use for endometrial sampling for women with
      menorrhagia, and to establish the preferred medical therapy for menorrhagia. A
      postal survey of all practising gynaecologists in New Zealand was undertaken.
      Questions were asked regarding which women with menorrhagia should have an
      endometrial biopsy, what sampling method they used, and their first, second and
      third line medical treatments. There were 68 replies (48% response rate). There
      was no general agreement on the mean age at which women with menorrhagia should
      have an endometrial sample. Forty-six percent preferred hysteroscopy to sample
      the endometrium, and 41% preferred a pipelle suction curette. The most favoured
      first-line choice used to treat menorrhagia was luteal phase progestogens (54%).
      The most-favoured second choice was the nonsteroidal antiinflammatory drugs
      (NSAIDs), and the most favoured third choice was danazol. The results from this
      study suggested that protocols need to be developed in order to prevent women
      with menorrhagia from being inappropriately investigated or suboptimally treated.
      It is possible that the high hysterectomy rate in New Zealand could be reduced if
      gynaecologists were to use more effective treatment earlier in the clinical
      presentation of menorrhagia.

PMID- 9006832
TI  - Endometrial resection--a comparison of techniques.
AB  - To assess the long-term effectiveness and safety of endometrial resection, an
      ongoing prospective study of 927 patients, followed for 1 to 5 years, was carried
      out. The patients met criteria previously adopted for vaginal hysterectomy. Three
      techniques were used, modified over time with experience gained and failures
      encountered: Technique 1: Resection alone; Technique 2: Resection, followed by
      roller-ball cautery of the whole endometrium; Technique 3: Laparoscopic control,
      resection, roller-ball cautery, further resection especially in the cornua and
      fundus and finally laparoscopic cautery of the cornual region of the uterus.
      Various parameters were measured including preparation of the endometrium,
      pathology present, complications and outcomes. There was a marked improvement in
      the success of the procedure with changes from Technique 1 to 2 to 3. There was a
      fall in the failure rate from 22% to 5%. These results were statistically highly
      significant (p < 0.0001). The best results obtained were in women with
      endometrial polyps and pure dysfunctional bleeding with good results in cases of
      intramural fibroids and adenomyosis. There were no deaths and no cases of long
      term adverse sequelae resulting from complications, but the following were
      encountered: perforation of the uterus, hyponatraemia, pregnancy, infection,
      unanticipated malignancy and cervical stenosis. It is concluded that in view of
      the high success rate and relative lack of serious complications, endometrial
      ablation should be considered the treatment of choice in cases of dysfunctional
      bleeding in women who have completed their families.

PMID- 9006834
TI  - Abdominal hysterectomy. Complications, hospital stay and cost.

PMID- 9006833
TI  - The intravaginal slingplasty operation, a minimally invasive technique for cure
      of urinary incontinence in the female.
AB  - The aim was to evaluate the intravaginal slingplasty operation, a minimally
      invasive technique for cure of urinary incontinence. Fifty-four unselected
      patients, aged from 26 to 79 years, mainly with mixed incontinence symptoms,
      underwent this procedure. It works by tightening the suburethral vagina
      ('hammock'), and by creating an artificial pubourethral neoligament. Where
      indicated, repair of uterine prolapse (24 cases), or infracoccygeal sacropexy (17
      cases) was also performed. Almost all patients were discharged on the day of, or
      day after surgery, without requirement for postoperative catheterization, and
      returned to fairly normal activities, including jobs, within 7 to 14 days. At a
      mean follow-up time of 15 months, the cure rates for preoperative symptoms were,
      frequency 88%, nocturia 77%, urge incontinence 89%, stress incontinence (SI) 85%,
      symptoms of abnormal emptying, 77%, and reduction of mean residual urine from
      67.5 mL to 32 mL. The objective cure rate (exercise pad testing) for stress
      incontinence was 88.6%; taking the group as a whole, urine loss was reduced from
      a mean of 11.6 g preoperatively to a mean of 0.5 g postoperatively.
      Urodynamically diagnosed detrusor instability was not a predictor of surgical
      failure in this study. According to the concepts presented here, symptoms of
      urinary dysfunction are mainly symptomatic manifestations of abnormal laxity in
      the vagina or its supporting ligaments. The surgical methods used to correct
      these defects are fairly simple, safe and easily learnt by an practising
      gynaecologist.

PMID- 9006835
TI  - Removal of fibromyomas by laparoscopic surgery after preoperative GnRH analogue-
      an alternative to abdominal hysterectomy or myomectomy.
AB  - Nineteen patients with fibromyomas who had been recommended to have a
      hysterectomy or abdominal myomectomy were referred as they wished to avoid a
      hysterectomy (14) or laparotomy incision for a myomectomy (5). Following
      administration of the GnRH analogue goserelin, laparoscopic surgery was performed
      on all these patients. Hysterectomy was avoided in all but 1 of the 14 patients
      and laparotomy myomectomy was avoided in 4 of the 5 patients recommended to have
      these procedures. The combination of a GnRH analogue and laparoscopic-based
      surgery may be an acceptable alternative to both laparotomy myomectomy and
      hysterectomy in women with fibromyomas requiring surgery.

PMID- 9006836
TI  - Management of ovarian remnant syndrome.
AB  - Ovarian remnant syndrome is a rare condition which develops when functional
      ovarian tissue which is left in situ after intended bilateral oophorectomy
      produces clinically significant symptoms, namely chronic pelvic pain and/or
      dyspareunia. Women with this syndrome may have a pelvic mass palpable on bimanual
      examination, or visible on transvaginal ultrasound. However, visualization of an
      ovarian remnant is sometimes difficult because it is small and multiple previous
      pelvic operations have usually produced dense adhesions and distorted pelvic
      anatomy. Identification of these remnants may be facilitated by ovarian
      stimulation. Surgical removal is the optimal treatment, but hormonal suppression
      of ovarian activity may provide temporary relief of pain.

PMID- 9006837
TI  - Phaeochromocytoma in pregnancy.
AB  - The Royal Women's Hospital, Melbourne, is a tertiary referral hospital with over
      7,000 deliveries per year. We report 3 cases of phaeochromocytoma in pregnancy at
      the hospital in the 20-year period since 1976. The first case was unsuspected and
      resulted in a maternal death. The subsequent 2 cases were diagnosed antenatally
      with successful outcomes for both mother and baby. The 3 cases demonstrate the
      importance of an early antenatal diagnosis and the special management problems of
      phaeochromocytoma in pregnancy. The diagnosis of phaeochromocytoma should be
      considered in any pregnant women with severe hypertension, particularly if
      presenting before 20 weeks' gestation, labile, or associated with sweating,
      palpitations or headaches.

PMID- 9006838
TI  - Placenta praevia accreta with delayed hysterectomy.
AB  - A case of placenta praevia accreta is described. Delivery was achieved by
      Caesarean section and the placenta was left in place because of the risk of
      haemorrhage. Successful internal iliac artery embolization was performed 9 days
      postpartum to control uterine bleeding. Hysterectomy was performed at 55 days
      postpartum because of bleeding and sepsis.

PMID- 9006839
TI  - Laparoscopic ovarian cystectomy in pregnancy.

PMID- 9006840
TI  - The use of intraoperative ultrasound in the management of a perforated uterus
      with retained products of conception.
AB  - The benefits of non-invasive, correctly-directed instrumentation coupled with an
      ability to predict complete evacuation of the uterus can make intraoperative
      ultrasound an important addition in the continued and improved care of women with
      a perforated uterus and retained products of conception. Two such cases are
      reported.

PMID- 9006841
TI  - Pregnancy during gonadotrophin-releasing hormone agonist therapy.

PMID- 9006842
TI  - Spurious elevation of luteinizing hormone.

PMID- 9006843
TI  - Low dose ketoconazole is an effective and a relatively safe alternative in the
      treatment of hirsutism.
AB  - Efficacy, clinical and hormonal effect of ketoconazole in 400 mg/day dose was
      tested in a prospectively-designed study. Twenty four patients with hirsutism
      according to the Ferriman and Gallwey score (> 8) and elevated blood androgen
      levels were administered 400 mg/day ketoconazole for 6 months. Basal and
      posttherapy early follicular phase androgens and biochemical parameters were
      evaluated. In 22 patients significant improvement and in 2 slight improvement was
      seen in subjective complaints. No side-effects were observed in these patients
      other than 2 cases of pruritus (transient), 2 mild gastric upset and 1
      mastodynia. All patients completed the study. Low dose ketoconazole seems to be
      effective in the treatment of hirsutism with relatively few side-effects but
      still should be reserved as an alternative choice due to the potential for
      deleterious hepatic effects.

PMID- 9006844
TI  - Acute massive haemoperitoneum due to mild pelvic endometriosis.

PMID- 9006845
TI  - Macrofolliculoid granulosa cell tumour mistaken for a polycystic ovary at
      ultrasound scan.

PMID- 9006846
TI  - Leiomyoma of the vagina.
AB  - Approximately 250 cases of leiomyoma of the vagina have been reported. A case of
      a 46-year-old female with leiomyoma of the anterior vaginal wall, not associated
      with uterine leiomyomas is presented. The practical approach to such a vaginal
      mass entails immediate careful excision.

PMID- 9006847
TI  - Gestational diabetes: a syndrome.

PMID- 9006848
TI  - Re: Invasive cervical cancer in pregnancy.

PMID- 9006849
TI  - Re: Shoulder dystocia.

PMID- 9006850
TI  - Vaginal delivery after caesarean section: factors influencing success rates.

PMID- 9006851
TI  - Re: Peritoneal surgery in the treatment of endometriosis--excision or thermal
      ablation?

PMID- 9006852
TI  - Taskforce investigates fatal bat virus.

PMID- 9006853
TI  - Do alternative (acupuncture, herbalism, homeopathy etc) have a role in your
      practice?

PMID- 9006854
TI  - A lame dog with distal tibial swelling.

PMID- 9006855
TI  - Cryptococcal meningitis in an alpaca.

PMID- 9006856
TI  - Nocardial peritonitis in a cat.
AB  - OBJECTIVE: To illustrate a successfully managed case of nocardial peritonitis in
      a cat. DESIGN: Case report. ANIMAL: An 8 year old neutered male Burmese cat
      presented for nonspecific signs of depression, anorexia, pallor and mild
      dehydration. Pyrexia, loss of weight and abdominal distension developed despite
      treatment with amoxycillin-clavulanate and supportive therapy. PROCEDURE: Various
      medical and surgical procedures were used. RESULTS: Haematology revealed severe
      inflammatory left shift. Biochemistry showed mild prerenal azotemia. A "ground
      glass" appearance to the abdomen was seen on radiographs. Fluid collected by
      abdominocentesis contained "sulphur granules" and had characteristics of a septic
      exudate. Laparotomy allowed drainage of peritoneal fluid and extensive lavage of
      the peritoneal cavity. Culture of the fluid revealed Nocardia sp. Sensitivity
      testing resulted in a change of antimicrobial therapy to trimethoprim
      sulphadiazine. CONCLUSION: Response to surgical drainage and change in
      antibacterial therapy was excellent. No toxic side effects were encountered
      during the 3 months course of trimethoprim-sulphonamide. The cat made a complete
      recovery.

PMID- 9006857
TI  - Low IgA concentration in the tears of German shepherd dogs.

PMID- 9006858
TI  - Persistent corneal erosion in an Australian dingo.

PMID- 9006859
TI  - Meningoencephalitis and brain abscessation due to Escherichia coli in a 2 week
      old alpaca cria.
AB  - An alpaca cria which received insufficient colostrum, presented with lethargy,
      anorexia, no passage of faeces and neurological signs. Differential diagnosis
      included neonatal septicaemia, meningitis and gastrointestinal obstruction. The
      cria died despite treatment. Necropsy revealed brain abscesses with Escherichia
      Coli in pure culture. The importance of the amount and timing of colostrum intake
      is discussed.

PMID- 9006860
TI  - Therapeutic compliance.

PMID- 9006861
TI  - Comparison of methods to assess dog owners' therapeutic compliance.
AB  - OBJECTIVE: To compare different methods for assessing the compliance of
      veterinary clients administering medication to their dogs. PROCEDURE: Thirty-one
      owners whose dogs were prescribed amoxycillin-clavulanate, twice and thrice
      daily, for a duration of five to seven days were recruited from three Sydney
      veterinary hospitals. Compliance was assessed by electronic monitoring devices,
      return medication counts, client self-reports and veterinarians' estimation of
      likely compliance. RESULTS: Electronic monitoring showed owners administered on
      average 84% (range 7 to 104%) of prescribed medication to their dogs. Both return
      medication counts and client self-reports tended to overestimate therapeutic
      compliance when compared with electronic monitoring. When questioned, the
      majority of owners (71%) claimed perfect compliance with the prescribed regimen.
      No correlation was found between veterinarians' estimates of owner compliance and
      that assessed electronically. CONCLUSION: Electronic monitoring provided valuable
      information on dose timing and variation, but proved costly and difficult to
      employ in veterinary practice. Simplicity and low cost of return medication
      counts makes this method attractive for use in veterinary compliance studies.
      Client self-reports reliably detected some noncompliers and permitted
      identification of individual problems or errors. For practical purposes a
      combination of return medication counts and client self-reports may have merit in
      future veterinary compliance studies.

PMID- 9006862
TI  - Field trial of a staphylococcal mastitis vaccine in dairy herds: clinical,
      subclinical and microbiological assessments.
AB  - OBJECTIVE: To assess the efficacy of a new staphylococcal mastitis vaccine under
      commercial dairying conditions. DESIGN: A field trial involving 1819 cows and
      heifers conducted on seven dairy herds in Victoria. The trial was done 'blind';
      approximately half the animals were vaccinated and the remainder were untreated
      controls. PROCEDURE: The vaccine was given twice during the last 10 weeks of
      pregnancy. Effects of vaccination were assessed, during the ensuing lactation, on
      the basis of clinical and sub-clinical mastitis and microbiological
      investigations of the milk. RESULTS: A total of 273 cases of clinical mastitis
      were recorded. Staphylococcus aureus was isolated from 112 of these, 45 cases in
      vaccinates and 67 cases in controls; the difference was not statistically
      significant. One herd was notable in having a high incidence of clinical
      staphylococcal mastitis. This herd accounted for 15.8% of the animals in the
      field trial but 54.5% of cases of clinical staphylococcal mastitis. For this
      herd, vaccinated animals had significantly lower incidence of clinical
      staphylococcal mastitis and prevalence of subclinical mastitis, relative to
      controls. An unexpected feature of the trial as a whole was the low incidence of
      clinical mastitis from which S aureus was isolated in pure culture (26.3% of
      cases) and the high incidence of clinical Streptococcus uberis mastitis (22.7% of
      cases). CONCLUSIONS: The trial showed that the vaccine was efficacious in
      reducing the incidence of clinical mastitis and prevalence of subclinical
      mastitis in a herd that had a serious staphylococcal mastitis problem.

PMID- 9006863
TI  - Effect of adjuvants on antibody responses of sheep immunised with recombinant
      pili from Dichelobacter nodosus.
AB  - OBJECTIVE: To compare the effects of two oil emulsion adjuvants (incomplete
      Freunds adjuvant and a proprietary oil adjuvant), DEAE-dextran, L-tyrosine
      particles and Quil A on the humoral immune responses of sheep immunised with
      recombinant pili of Dichelobacter Nodosus (strain A). PROCEDURE: Antibody titres
      were studied for up to 32 weeks and were measured by bacterial agglutination and
      ELISA. The relative avidity of antibodies for pili was determined and the
      incidence and severity of adverse reactions at the site of injection of vaccines
      were recorded. RESULTS: The oil emulsion adjuvants and Quil A were more effective
      than either DEAE-dextran or L-tyrosine at stimulating antibodies in sheep. The
      incidence and severity of adverse reactions was lower in sheep which received
      vaccines containing either Quil A or DEAE-dextran than in sheep which received
      vaccines containing oil emulsion adjuvants. L-tyrosine had no adverse effects.
      CONCLUSION: Quil A was as effective as oil adjuvants at stimulating high levels
      of antibodies against recombinant pili in sheep and had the significant advantage
      of being less irritant after subcutaneous injection.

PMID- 9006864
TI  - Responses in milk production to control of gastrointestinal nematode and
      paramphistome parasites in dairy cattle.
AB  - OBJECTIVE: To determine the effect of treating naturally acquired
      gastrointestinal nematode and paramphistome infections on milk production in
      dairy cattle. DESIGN: A field trial. ANIMALS: One thousand two hundred and thirty
      nine dairy cows. PROCEDURE: Cows were either not treated or treated with 4.5
      mg/kg oxfendazole, 16.6 mg/kg oxyclozanide or 4.5 mg/kg oxfendazole and 16.6
      mg/kg oxyclozanide in March, May and August. RESULTS: A significant increase in
      milk production, averaging 0.4 L (SE 0.2) per day, was seen when dairy cows
      infected with gastrointestinal nematodes and paramphistomes were treated with
      oxfendazole or oxfendazole and oxyclozanide in March, May and August. Cows
      treated with oxyclozanide alone at these times produced no more milk than
      untreated cows. Faecal egg counts confirmed that oxyclozanide treatment reduced
      paramphistome populations and oxfendazole treatment reduced nematode populations
      in cows over the 7-month monitoring period. CONCLUSION: When dairy cows infested
      with gastrointestinal nematodes and paramphistomes were treated with oxfendazole
      alone or oxfendazole and oxyclozanide in March, May and August milk production
      increased.

PMID- 9006865
TI  - Open reduction and stabilisation of coxofemoral joint luxation in dogs and cats,
      using a stainless steel rope inserted via a ventral approach to the hip joint.
AB  - Open reduction and stabilisation of coxofemoral joint luxation was made via a
      ventral approach to the hip joint in dogs and cats, using a transarticular
      stainless steel rope. A feature of the procedure is transarticular penetration of
      the rope from the pelvic cavity to the femoral neck by guidance with a guide wire
      which was previously inserted from the femoral neck into the pelvic cavity and by
      detection of the guide wire in the pelvic cavity by use of forceps connected to
      an alarm-ohmmeter. Forty-seven animals (37 dogs and 10 cats) with acute and
      simple coxofemoral luxation were treated and postoperatively maintained in cage
      rest without external fixation. Most of the animals regained an almost normal
      gait within several days.

PMID- 9006866
TI  - Marek's disease vaccination of chickens.

PMID- 9006867
TI  - Lack of toxicity of Ailanthus altissima (tree-of-heaven) for goats.

PMID- 9006869
TI  - The prevalence of intestinal spirochaetes in dogs.

PMID- 9006868
TI  - Annual ryegrass toxicosis in horses.

PMID- 9006870
TI  - Suppression of Boophilus microplus populations with fluazuron--an acarine growth
      regulator.

PMID- 9006871
TI  - Heart rate as a measure of adaptation to stress in cattle.

PMID- 9006872
TI  - The use of pound dogs in teaching and research.

PMID- 9006873
TI  - Tail docking.

PMID- 9006874
TI  - More care, less haste.

PMID- 9006875
TI  - Subjective postural orientation and visual vertical during slow pitch tilt for
      the seated human subject.
AB  - METHODS: To assess subjective postural orientation and the visual vertical during
      slow pitch tilt, subjects were seated, restrained and in darkness in a simulator.
      They estimated when they were tilted 0 degrees, 45 degrees, and 90 degrees
      forwards and backwards during cycles of pitching tilted at 1 degree x s-1 and at
      the same time set a 5-cm luminous cube, cockpit-mounted at 60 cm from the nasium,
      to be Earth vertical. Experimental protocols assessed the following: 1) the
      effect on postural estimates of seeing the cube versus darkness; 2) comparison of
      visual vertical settings at actual 45 degrees and 90 degrees tilts; 3) the
      adaptive effect of repeating estimates and settings; 4) the effect of a prolonged
      tilt on subsequent postural and visual vertical estimates; and 5) the comparative
      effect of tilting the body in alignment. RESULTS: Seated, subjects' estimates of
      postural tilt were consistently greater than machine tilt, and similar in
      darkness to when seeing the cube. Overestimations increased with preceding tilts
      in the opposite direction, particularly when tilting from forwards whence
      subjects estimated they were backwards when the machine was tilted forwards.
      Postural estimates became more accurate with repetition but visual verticals
      deteriorated. Duration of conditioning tilt did not effect estimates. Visual
      vertical settings were largely accurate throughout. Labyrinthine defective
      subjects performed similarly to normals. Subjects frequently reported they felt
      disoriented during tilting. DISCUSSIONS: Seated subjects' postural estimates were
      'accurate' if one assumes that the reference shifted from the head to a trunk-leg
      axis on backwards tilt, however, subjects were unaware of this. Postural and
      visual vertical estimates could have been based solely on proprioception. Shifts
      in reference for verticality could be a factor in misperception of attitude in
      air and ground vehicles when accelerating or climbing.

PMID- 9006876
TI  - Disorientation and postural ataxia following flight simulation.
AB  - BACKGROUND: Motion sickness-like symptoms can afflict pilots training in military
      simulators. This simulator sickness involves symptoms of gastrointestinal
      distress, eyestrain and disorientation. A simulator sickness Questionnaire (SSQ)
      with subscales available for each of these dimensions has been developed to
      assess the problem. HYPOTHESIS: This study examined the hypothesis that there is
      a strong correlation between the SSQ subscale which summarized self report of
      disorientation symptoms and an objective measure of post-simulation postural
      instability. METHODS: Data from two Navy simulators were analyzed: Device 2F114,
      a Weapon System Trainer for the A-6E Intruder, and Device 2F143, an Operational
      Flight Trainer for the EA-6B. Tests of standing and walking unsteadiness were
      administered along with the Simulator Sickness Questionnaire (SSQ). RESULTS:
      Significant correlations were found between scores on postural stability tests
      and the SSQ disorientation subscale scores, but correlations between scores on
      postural stability tests and the SSQ nausea and oculomotor subscale scores were
      much weaker and not statistically significant. CONCLUSIONS: These results provide
      some evidence for the validity of the disorientation subscale of the SSQ and
      suggest that the postural instability observed after simulator exposure may, in
      fact, result from disorientation.

PMID- 9006877
TI  - A study of USAF air traffic controller shiftwork: sleep, fatigue, activity, and
      mood analyses.
AB  - BACKGROUND: The purpose of this study was to evaluate the shift-specific sleep,
      general activity levels, mood and cognitive performance of air traffic
      controllers (ATCs) working a forward 2-2-2 rapid rotation shift schedule.
      HYPOTHESIS: ATCs are more fatigued on the night-shift. METHODS: ATCs recorded
      their sleep, oral temperature and subjective fatigue levels, took a computerized
      cognitive performance battery (n = 13) and completed the Profile of Mood States
      questionnaire (POMS) (n = 12). Actigraphs were used to objectively monitor
      general activity levels and score sleep and the restfullness of scored sleep (n =
      9). Analyses were made on the basis of duty shift, post-shift, day of shift, and
      duty location. RESULTS: There was significantly more actigraph scored sleep (85
      min, p = 0.038), subjectively reported sleep (26 min, p = 0.009) and subjectively
      measured fatigue (p < 0.001) and confusion (p = 0.003) for the ATCs while they
      were on-duty on the night-shift. The night-shift was also associated with
      decreased vigor (p = 0.039) and general activity levels (p = 0.017).
      Significantly more sleep was reported (7.6 h, p = 0.01) and scored by actigraph
      (4.7 h, p = 0.02) following the swing-shift than following the day-shift. The
      radar approach ATCs reported greater confusion (p = 0.019) and less vigor (p =
      0.002) than the tower ATCs. Insufficient trials were available for direct
      performance analysis. CONCLUSIONS: ATCs on the night-shift of a forward rapid
      rotation shift schedule appear to be falling asleep and report increased
      confusion and fatigue. Further study is indicated.

PMID- 9006878
TI  - Height increase, neuromuscular function, and back pain during 6 degrees head-down
      tilt with traction.
AB  - BACKGROUND: Spinal lengthening and back pain are commonly experienced by
      astronauts exposed to microgravity. METHODS: To develop a ground-based simulation
      for spinal adaptation to microgravity, we investigated height increase,
      neuromuscular function and back pain in 6 subjects all of whom underwent two
      forms of bed rest for 3 d. One form consisted of 6 degrees of head-down tilt
      (HDT) with balanced traction, while the other was horizontal bed rest (HBR).
      Subjects had a 2-week recovery period in between the studies. RESULTS: Total body
      and spinal length increased significantly more and the subjects had significantly
      more back pain during HDT with balanced traction compared to HBR. The distance
      between the lower endplate of L4 and upper endplate of S1, as measured by
      ultrasonography, increased significantly in both treatments to the same degree.
      Intramuscular pressures in the erector spinae muscles and ankle torque
      measurements during plantarflexion and dorsiflexion did not change significantly
      during either treatment. CONCLUSION: Compared to HBR, HDT with balanced traction
      may be a better method to simulate changes of total body and spinal lengths, as
      well as back pain seen in microgravity.

PMID- 9006880
TI  - Liferaft evacuation from a ditched helicopter: dry shod vs. swim away method.
AB  - METHODS: There were 23 male and 21 female subjects who conducted a series of
      evacuations from the NUTEC Super Puma helicopter simulator into an RFD heliraft
      in the Bergen Fjord. The dry shod and swim-away methods were compared both on the
      windward and leeward side. RESULTS: The dry shod method is the method of choice,
      although the swim-away method should be taught as an alternative in the event of
      imminent capsizing. Irrespective of method, evacuation wherever possible should
      be on the windward side. CONCLUSIONS: Because it is critical for the aircrew to
      make a split-second decision concerning which method to use, they should have
      special training in open water after traditional pool training.

PMID- 9006879
TI  - Urinary 5-hydroxytryptophol following acute ethanol consumption: clinical
      evaluation and potential aviation applications.
AB  - HYPOTHESIS: The unknown prevalence of alcohol use and misuse among aviation
      pilots, crewmembers and associated support personnel call for continuous
      improvement of methods for detecting recent alcohol use. Early detection is
      essential to proper treatment and prevention of potentially catastrophic mishaps.
      Urinary 5-hydroxytryptophol (5HTOL), a serotonin (5HT) metabolite, has shown
      promise in the clinical setting as a noninvasive marker of recent alcohol
      consumption. METHODS: The urinary 5HTOL concentrations of 11 male and female
      subjects were followed for approximately 24 h following dosing with ethanol 0.6
      g.kg-1. Concentrations were reported as a ratio of 5HTOL to 5-hydroxy
      indoleacetic acid (5HIAA), 5HTOL/5HIAA (pmol/nmol), to compensate for urinary
      dilution and elevated 5HTOL levels due to dietary intake. Data from one male
      subject was excluded after he admitted to continued alcohol consumption
      subsequent to dosing and missing several urine samples. RESULTS: 5HTOL/5HIAA
      ratios remained above the 15 pmol/nmol cutoff for recent alcohol use for
      approximately 11-16 h in all except one subject. Calculations based on body
      weight and administered alcohol dose suggest that measurable blood alcohol levels
      would exist for only 5-7 h post ingestion. CONCLUSION: This study confirmed the
      extended elevation of 5HTOL/5HIAA ratios observed in earlier studies, even at the
      relatively low alcohol dose used herein. 5HTOL appears to be a marker for acute
      alcohol consumption worthy of further investigation by military and civilian
      authorities. Potential aviation applications of 5HTOL include validation of
      measurable blood alcohol concentrations, investigation of poor performance due to
      hangover effects, and as a forensic toxicology tool in aircraft accident
      investigations to distinguish between actual alcohol ingestion and post-mortem
      alcohol synthesis.

PMID- 9006882
TI  - Suppression of the reactive hyperemic response in the forearm due to local hand
      cooling.
AB  - METHODS: Forearm blood flow (FBF) was measured by electrical impedance
      plethysmography in order to identify the influence of local cooling of the
      contralateral hand after 3 min of arterial occlusion. Ten volunteers (six
      females, four males) were randomly assigned to the following three experimental
      conditions on separate days: a) 6 min of local hand cooling (5-7 degrees C); b) 3
      min of arterial occlusion of the forearm; and c) combined arterial occlusion and
      local cooling. RESULTS: All subjects experienced the typical pressor response
      during 6 min of hand cooling as evidenced by the significant increase (p < and =
      0.05) in heart rate (HR), systolic blood pressure (SBP), and diastolic blood
      pressure (DBP). The FBF responses demonstrated an immediate increase (p < and =
      0.05) within the first 30 s of hand submersion and then progressively declined
      over the next 5 min. The forearm vascular resistance (FVR = MAP/FBF) made an
      initial drop during the first 30 s of cooling and then gradually rose to reach
      peak levels between 5-6 min of cooling. With respect to the hyperemic response,
      FBF significantly increased (p < and = 0.05) from baseline (mean +/- SEM; 1.09 +/
      0.18 ml x 100 ml-1.min-1) and achieved peak levels (6.75 +/- 0.64 ml x 100 ml
      1.min-1) within the initial 30 s of the post-occlusion period. Thereafter, FBF
      declined rapidly by 30-60 s (1.67 +/- 0.29 ml x 100 ml-1.min-1) and 60-90 s (1.26
      +/- 0.33 ml x 100 ml-1.min-1) of the post-occlusion period. CONCLUSION: When the
      reactive hyperemic response was coupled with hand cooling, FBF increased above
      baseline values and reached peak levels during the initial 30 s of the post
      occlusion period. However, the magnitude of the hyperemic response was
      significantly lower in the cold condition compared to the hyperemia alone (3.20
      +/- 0.42 vs 6.75 +/- 0.64 ml x 100 ml-1.min-1; p < and = 0.05). Clearly, the
      overall sympathetic response to local cooling had an overriding effect on the
      factors that promote peripheral vasodilation following brief periods (3 min) of
      arterial occlusion.

PMID- 9006881
TI  - Physiological and psychological effects associated with high carbon dioxide
      levels in healthy men.
AB  - BACKGROUND: Perception of CO2 in ambient air may be of fundamental importance to
      the health, safety, and job performance of persons occupationally exposed to
      increased levels of CO2. Few studies have examined the perceptual responses to
      inhaled CO2 at levels between 6-10%. HYPOTHESIS: We hypothesized that healthy,
      highly-active men would be able to determine the difference between 6% and 8% CO2
      concentrations. METHODS: Thirty-two male students (21 +/- 1 yr) served as
      subjects. Experimental trials (counterbalanced design) included breathing air
      (control, 21% O2, 79% N2), 6% CO2 (21% O2, 73% N2), and 8% CO2 (21% O2, 71% N2)
      conditions. The Body Sensations Questionnaire (BSQ) was completed twice during
      each trial. RESULTS: End tidal CO2 (FETCO2) and BSQ values increased (p < 0.05)
      as a function of the percentage of inhaled CO2. Respiratory rates during the 8%
      trial were greater (p < 0.05) than control and 6% CO2 trial measures. BSQ scores
      were significantly correlated with FETCO2 and respiratory rate measures during
      the 6% and 8% CO2 conditions. CONCLUSIONS: We conclude that these subjects
      recognized their exposure to both the 6% and 8% CO2 concentrations, and their
      responses were more profound during the 8% CO2 condition.

PMID- 9006884
TI  - Military and civilian emergency aeromedical services: common goals and different
      approaches.
AB  - Military and civilian organizations in the U.S. operate separate but parallel
      emergency aeromedical services. Despite common origins, military and civilian
      approaches and methods have diverged. This article compares and contrasts the
      capabilities, priorities, safety, equipment, training and personnel of the
      largest military service, the U.S. Army, to civilian rotary wing (helicopter)
      emergency aeromedical programs. The different successes of military and civilian
      emergency aeromedical programs can be considered for use to improve the services
      of each. In general, Army programs operate larger aircraft and utilize two pilots
      per aircraft. Safety is a high priority and the Army aeromedical safety record is
      excellent. The Army also places a high degree of emphasis on crashworthiness and
      protective gear for the crew. Most civilian air Emergency Medical Service (EMS)
      programs operate small to moderate-sized aircraft flying with a single pilot. The
      recent safety record has improved dramatically. Civilian programs may add to
      their safety by considering two pilots and incorporating the crashworthy and
      protective advancements made by the military. Civilian programs fly with two
      highly trained medical technicians, nurses or physicians, equipped with state-of
      the-art medical equipment. Army helicopters fly with one lesser-trained medical
      crewmember and less equipment. Improved combat casualty care and battlefield
      survival may be possible by increasing both the number and training of the
      medical attendants on Army aircraft.

PMID- 9006883
TI  - At work and play in a hazardous environment: injuries aboard a deployed U.S. Navy
      aircraft carrier.
AB  - BACKGROUND: A deployed U.S. Navy aircraft carrier is a hazardous environment
      where work and recreation intermingle. Injuries causing time lost from assigned
      duties may impact aviation safety and operational readiness. This descriptive
      study examines injuries sustained on the flight deck, in the hangar bay, or in
      the gym of a deployed aircraft carrier, focusing on those injuries resulting in
      lost duty days. METHODS: Injuries recorded by the ship's medical department were
      analyzed, relating lost duty injuries to the following parameters: division,
      rank, time of day, location of injury event, whether injury was job-related or
      recreational, type of recreational activity, and mechanism, type, and anatomic
      site of injury. RESULTS: During a 6-mo deployment, 335 injuries occurred in the
      shipboard locations studied. More than one-third (36%) of these injuries resulted
      in lost duty time, accounting for 768 man-days of lost duty during the
      deployment. Recreational injuries represented 19% of all injuries, but 25% of all
      lost duty injuries, a statistically significant contribution to lost duty time
      when compared to job-related injuries (p = 0.04). The sports of basketball,
      volleyball, and football were more likely than other recreational activities to
      cause injuries resulting in lost duty time (p = 0.01). Musculoskeletal injuries,
      particularly injuries involving the lower extremity, neck, and back, were also
      associated with increased risk of lost duty time (p < 0.001). CONCLUSIONS:
      Although recreational injuries are less frequent than job-related injuries in the
      study population, they contribute disproportionately to lost duty time. Injury
      prevention in similar environments should address recreational as well as work
      related activities.

PMID- 9006885
TI  - Predictors of barotrauma events in a Navy altitude chamber.
AB  - BACKGROUND: Barotrauma in the flight environment is a significant cause of
      incidents and mishaps. Upper respiratory infections and allergic rhinitis are
      considered to increase the risk of barotrauma in the changing pressure
      environment. In an attempt to identify antecedent conditions as predictors of
      barotrauma, all adverse outcomes which occurred in a Navy altitude chamber during
      1993-94 were investigated. METHODS: A retrospective study of chamber logs, pre
      chamber screening questionnaires, and a medical waiver database was conducted on
      altitude chamber trainees at the Naval Aerospace and Operational Medical
      Institute. Barotrauma cases were confirmed by reviewing ENT consultation records.
      Chamber screening questionnaires and medical waiver status were compared between
      barotrauma cases and a control group from the same chamber runs. RESULTS: Of 5851
      trainees, 193 (3.3%) experienced adverse events during this period, with an
      additional 9 events occurring to inside observers. Barotrauma, with 160 cases,
      accounted for the greatest number of these events. Upper respiratory symptoms
      were present in 12 (7.7%) of the barotrauma cases and 15 (4.8%) of the controls.
      Waivers for upper respiratory conditions such as allergic rhinitis were present
      in 9 (6.1%) of the barotrauma cases and 17 (5.7%) of the controls. Under
      reporting of upper respiratory conditions on pre-chamber screening was found
      however, with only 7 of 28 cases with recent cold symptoms reporting this prior
      to chamber training. CONCLUSIONS: No significant differences were found in
      predictors for barotrauma between cases and controls in this study group.

PMID- 9006887
TI  - Air traffic controller shiftwork: what are the implications for aviation safety?
      A review.
AB  - Most civilian and military air traffic control facilities in the United States
      use rapid rotation shift schedules. These schedules have generally been chosen
      for social reasons. Safety concerns have been raised because the air traffic
      controllers (ATCs) often carry an acute sleep debt onto the night-shift where
      they have little active work to do as they sit in the dark at the nadir of their
      circadian rhythms. This paper reviews advancing and delaying rapid shiftwork
      schedules, ATC workload factors as they relate to error rates and safety, and
      potential countermeasures. Recent studies indicate that ATC performance declines
      on the night-shift and that ATCs may be falling asleep while on-duty. There is
      indirect evidence that ATC error rates are highest on the night-shift. There are
      only limited studies which have evaluated potential countermeasures. The
      operational significance of the problems associated with ATC shiftwork is not yet
      clear. Further study is needed.

PMID- 9006886
TI  - Laughter in the cockpit: gelastic seizures--a case report.
AB  - We present a case of gelastic seizures in a student naval aviator. He was noted
      to have uncontrollable fits of laughter on several occasions, but was not
      referred to his flight surgeon until he had a gelastic seizure while flying in
      formation, which jeopardized the safety of the flight. He had an aura consisting
      of lack of concentration, which was then followed by 10 s or less of hysterical
      laughter. For the previous year and a half, he had had frequent episodes of
      nocturnal laughter so loud that he woke members of his household and occasionally
      himself. His neurological evaluation was normal, except for an
      electroencephalogram (EEG) and a separate video recording, which documented the
      ictal nature of his events. Gelastic seizures have not previously been discussed
      in the literature of aerospace medicine. This case illustrates a rare condition
      that should be considered in patients presenting with inappropriate laughter, and
      serves as a reminder of the need for continuous, ongoing evaluation of all
      aircrew by the cognizant flight surgeon.

PMID- 9006888
TI  - Cabin air quality. Aerospace Medical Association.
AB  - Cabin Air Quality has generated considerable public and workers' concern and
      controversy in the last few years. To clarify the situation, AsMA requested the
      Passenger Health Subcommittee of the Air Transport Medicine Committee to review
      the situation and prepare a position statement. After identifying the various
      sources of confusion, we review the scientifically accepted facts in the
      different elements involved in Cabin Air Quality: pressurization, ventilation,
      contaminants, humidity and temperature. At the same time, we identify areas that
      need more research and make recommendations accordingly.

PMID- 9006889
TI  - Structural instability of a constitutively active G protein-coupled receptor.
      Agonist-independent activation due to conformational flexibility.
AB  - Mutations in several domains can lead to agonist-independent, constitutive
      activation of G protein-coupled receptors. However, the nature of the structural
      and molecular changes that constitutively turn on a G protein-coupled receptor
      remains unknown. Here we show evidence that a constitutively activated mutant of
      the beta2 adrenergic receptor (CAM) is characterized by structural instability
      and an exaggerated conformational response to ligand binding. The structural
      instability of CAM could be demonstrated by a 4-fold increase in the rate of
      denaturation of purified receptor at 37 degrees C as compared with the wild type
      receptor. Spectroscopic analysis of purified CAM labeled with the
      conformationally sensitive and cysteine-reactive fluorophore, N,N'dimethyl-N
      (iodoacetyl)-N'-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)ethylenediamine, further
      indicated that both agonist and antagonist elicit more profound structural
      changes in CAM than in the wild type protein. We propose that the mutation that
      confers constitutive activity to the beta2 adrenergic receptor removes some
      stabilizing conformational constraints, allowing CAM to more readily undergo
      transitions between the inactive and the active states and making the receptor
      more susceptible to denaturation.

PMID- 9006890
TI  - Constitutive activation of JAK1 in Src-transformed cells.
AB  - We have previously found that the signal transducer and activator of
      transcription (Stat) 3 is constitutively activated in cells stably transformed by
      the v-Src oncoprotein. While activation of Stat proteins has also been observed
      following epidermal growth factor or platelet-derived growth factor stimulation,
      Stat3 activation is more commonly associated with signaling through cytokine
      receptors and activation of the Janus family tyrosine kinases JAK1 or JAK2. We
      therefore investigated whether JAK1 or JAK2 were activated in Src-transformed
      cells. In three v-Src-transformed fibroblast cell lines (NIH3T3, Balb/c, and
      3Y1), JAK1 displayed increased tyrosyl phosphorylation compared to non
      transformed cells. The level of tyrosyl phosphorylation of JAK1 was significantly
      greater in NIH3T3 cells transformed by expression of v-Src or high levels of a
      constitutively active mutant of c-Src (Y527F) than in cells overexpressing the
      less transforming normal c-Src. Enzymatic activity of JAK1 was assessed using
      autophosphorylation assays. In anti-JAK1 immunoprecipitates from v-Src
      transformed NIH3T3 cells, a protein with the same migration as JAK1 showed
      substantially increased levels of 32P incorporation compared to
      immunoprecipitates from non-transformed cells. Similar results were obtained
      using anti-JAK2 immunoprecipitates; however, the level of JAK2 tyrosyl
      phosphorylation and 32P incorporation in anti-JAK2 immunoprecipitates were
      markedly lower than in anti-JAK1 immunoprecipitates. We conclude that JAK1, and
      possibly JAK2, are constitutively activated in Src-transformed cells, raising the
      possibility that Janus family kinases contribute to the constitutive activation
      of Stat3 previously observed in these cells and/or other properties of Src
      transformed cells.

PMID- 9006891
TI  - A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and
      CD81), and phosphatidylinositol 4-kinase.
AB  - Enzymatic and immunochemical assays show a phosphatidylinositol 4-kinase in novel
      and specific complexes with proteins (CD63 and CD81) of the transmembrane 4
      superfamily (TM4SF) and an integrin (alpha3beta1). The size (55 kDa) and other
      properties of the phosphatidylinositol 4-kinase (PI 4-K) (stimulated by nonionic
      detergent, inhibited by adenosine, inhibited by monoclonal antibody 4CG5) are
      consistent with PI 4-K type II. Not only was PI 4-K associated with alpha3beta1
      CD63 complexes in alpha3-transfected K562 cells, but also it could be co-purified
      from CD63 in untransfected K562 cells lacking alpha3beta1. Thus, TM4SF proteins
      may link PI 4-K activity to the alpha3beta1 integrin. The alpha5beta1 integrin,
      which does not associate with TM4SF proteins, was not associated with PI 4-K.
      Notably, alpha3beta1-CD63-CD81-PI 4-K complexes are located in focal complexes at
      the cell periphery rather than in focal adhesions. The novel linkage between
      integrins, transmembrane 4 proteins, and phosphoinositide signaling at the cell
      periphery may play a key role in cell motility and provides a signaling pathway
      distinct from conventional integrin signaling through focal adhesion kinase.

PMID- 9006892
TI  - Polyvalent cationic metals induce the rate of transferrin-independent iron
      acquisition by HL-60 cells.
AB  - The trivalent metals iron, aluminum, and gallium greatly increase the rate of
      iron acquisition from low molecular weight chelates by human myeloid cells. The
      present study explores the mechanism responsible. Gallium-induced iron
      acquisition was shown to lead to stable cellular association of iron, the
      magnitude of which varied with the chelate to which the iron was bound. The
      majority of this iron initially associated with the plasma membrane. Cellular
      depletion of ATP did not affect the response to gallium nor did it require the
      continued presence of extracellular gallium. However, continued cell association
      of gallium was needed as subsequent cellular exposure to metal chelators resulted
      in a rapid loss of the "induced" phenotype. Other trivalent metals (lanthanum and
      gadolinium) and tetravalent metals (tin and zirconium) but not divalent metals
      also induced iron acquisition. Neither enhanced iron reduction nor protein kinase
      C or tyrosine kinases appeared involved in gallium-mediated induction of iron
      acquisition. Exposure of HL-60 cells to polyvalent cationic metals results in a
      dramatic and sustained increase in the rate of iron acquisition from low
      molecular weight chelating agents. This could be important for the rapid
      clearance of iron by phagocytes from the extracellular environment at sites of
      local tissue damage.

PMID- 9006894
TI  - Isolation of the mouse aldose reductase promoter and identification of a tonicity
      responsive element.
AB  - Aldose reductase (AR; EC 1.1.1.21) is an oxidoreductase that catalyzes the NADPH
      dependent conversion of glucose to sorbitol, the first step of the polyol
      pathway. AR is of great interest due to its implication in the etiology of
      diabetic complications. In renal medullary cells, AR also plays an osmoregulatory
      role by accumulating sorbitol to maintain the intracellular osmotic balance
      during antidiuresis. We have previously cloned the AR cDNA from mouse kidney, and
      we report here the isolation of the mouse AR gene promoter. Transient
      transfection of chloramphenicol acetyltransferase reporter constructs containing
      various 5'-flanking regions of the mouse AR gene in CV1 cells led to the
      identification of a sequence spanning base pairs -1053 to -1040, required for an
      enhancer activity in hypertonic compared with isotonic cell culture conditions.
      This sequence is similar to the tonicity-responsive element first characterized
      in the betaine-gamma-aminobutyric acid transporter promoter.

PMID- 9006893
TI  - A 16-kDa protein functions as a new regulatory protein for Hsc70 molecular
      chaperone and is identified as a member of the Nm23/nucleoside diphosphate kinase
      family.
AB  - Cytoplasmic Hsc70 is a multifunctional molecular chaperone. It is hypothesized
      that accessory proteins are used to specify the diverse chaperone activities of
      Hsc70. A 16-kDa cytosolic protein (p16) co-purified with Hsc70 obtained from a
      fish hepatocyte cell line, PLHC-1. Hsc70 also co-immunoprecipitated with p16 from
      PLHC-1 cells and fish liver. p16 was identified as a member of the
      Nm23/nucleoside diphosphate (NDP) kinase family based on its amino acid sequence
      similarity, NDP kinase activity, and recognition by anti-human NDP kinase-A
      antibody. This antibody also co-immunoprecipitated Hsc70 and NDP kinase from
      human HepG2 cells. p16 monomerized Hsc70 and released Hsc70 from pigeon
      cytochrome c peptide (Pc) but not from FYQLALT, a peptide specifically designed
      for high affinity binding. Therefore, p16 may modulate Hsc70 function by
      maintaining Hsc70 in a monomeric state and by dissociating unfolded proteins from
      Hsc70 either through protein-protein interactions or by supplying ATP indirectly
      through phosphate transfer. p16 did not affect basal or unfolded protein
      stimulated ATPase activity of bovine brain Hsc70 using in vitro assays.
      Interestingly, bovine liver NDP kinase did not dissociate the Hsc70.Pc complex.
      In addition, two nonconservative amino acid subsitutions were found near the
      amino terminus of p16. Therefore, p16 may be a unique Nm23/NDP kinase that
      functions as an accessory protein for cytosolic Hsc70 in eukaryotes.

PMID- 9006895
TI  - Actin-binding protein-280 binds the stress-activated protein kinase (SAPK)
      activator SEK-1 and is required for tumor necrosis factor-alpha activation of
      SAPK in melanoma cells.
AB  - SEK-1, a dual specificity protein kinase that serves as one of the immediate
      upstream activators of the stress-activated protein kinases (SAPKs), associates
      specifically with the actin-binding protein, ABP-280, in vitro and in situ. SEK-1
      binds to the carboxyl-terminal rod segment of ABP-280, upstream of the ABP
      carboxyl-terminal dimerization domain. Activation of SEK-1 in situ increases the
      SEK-1 activity bound to ABP-280 without changing the amount of SEK-1 polypeptide
      bound. The influence of ABP-280 on SAPK regulation was evaluated in human
      melanoma cells that lack ABP-280 expression, and in stable transformants of these
      cells expressing wild type ABP, or an actin-binding but dimerization-deficient
      mutant ABP (ABPDeltaCT109). ABP-280-deficient cells show an activation of SAPK in
      response to most stimuli that is comparable to that seen in ABP-280-replete
      cells; ABP-280-deficient cells, however, fail to show the brisk tumor necrosis
      factor-alpha (TNF-alpha) activation of SAPK seen in ABP-replete cells and have an
      80% reduction in SAPK activation by lysophosphatidic acid. Expression of the
      dimerization-deficient mutant ABP-280 fails to correct the defective SAPK
      response to lysophosphatidic acid, but essentially normalizes the TNF-alpha
      activation of SAPK. Thus, a lack of ABP-280 in melanoma cells causes a defect in
      the regulation of SAPK that is selective for TNF-alpha and is attributable to the
      lack of ABP-280 polypeptide itself rather than to the disordered actin
      cytoskeleton that results therefrom. ABP-280 participates in TNF-alpha signal
      transduction to SAPKs, in part through the binding of SEK-1.

PMID- 9006896
TI  - Motif III S5 of L-type calcium channels is involved in the dihydropyridine
      binding site. A combined radioligand binding and electrophysiological study.
AB  - The alpha1 subunit of L-type voltage-dependent Ca2+ channels (alpha1C) has been
      shown to harbor high affinity binding sites for the Ca2+ channel dihydropyridine
      (DHP) modulators. It has been suggested by a number of investigators that the
      binding site may be composed of III S6 and IV S6. Evidence with chimeric channels
      indicated the possible involvement of III S5 in DHP binding. Site-directed
      mutations were introduced in motif III S5 region of the alpha1C, changing the
      amino acids to their counterparts in the DHP-insensitive alpha1A channel. The
      mutant channels were expressed both in HEK 293 cells and in Xenopus oocytes.
      Equilibrium binding and electrophysiological studies showed that the Thr1006 to
      Tyr substitution produced a mutant channel with at least 1000-fold decreased
      affinity in [3H](+)isopropyl-4-(2,1, 3-benzoxadiazol-4-yl)-1,4-dihydro-(2, 6
      dimethyl-5-methoxycarbonyl)pyridine-3-carboxylate (PN200-110, isradipine) binding
      and in sensitivity of R(-)-4(2,1, 3-benzoxadiazol-4-yl)-1,4-dihydro-2, 6-dimethyl
      5-nitro-3-pyridincarboxylic acid isopropylester (R202-791) in terms of inhibition
      of current through the L-type voltage-dependent Ca2+ channels. Replacing Gln1010
      with Met resulted in more than a 10-fold decrease in binding affinity for
      [3H](+)PN200-110 and in the potency of channel modulation by S202-791. Four
      additional mutations in this region also lead to a slight but statistically
      significant increase of KD values for [3H](+)PN200-110 binding. The binding and
      electrophysiological results show that certain residues of the transmembrane
      segment III S5 are important in contributing to the DHP binding "pocket" and are
      critical for DHP binding and for its calcium channel effect.

PMID- 9006897
TI  - A peptide that mimics the C-terminal sequence of SNAP-25 inhibits secretory
      vesicle docking in chromaffin cells.
AB  - Excitation-secretion uncoupling peptides (ESUPs) are inhibitors of Ca2+-dependent
      exocytosis in neural and endocrine cells. Their mechanism of action, however,
      remains elusive. We report that ESUP-A, a 20-mer peptide patterned after the C
      terminus of SNAP-25 (synaptosomal associated protein of 25 kDa) and containing
      the cleavage sequence for botulinum neurotoxin A (BoNT A), abrogates the slow,
      ATP-dependent component of the exocytotic pathway, without affecting the fast,
      ATP-independent, Ca2+-mediated fusion event. Ultrastructural analysis indicates
      that ESUP-A induces a drastic accumulation of dense-core vesicles near the plasma
      membrane, mimicking the effect of BoNT A. Together, these findings argue in favor
      of the notion that ESUP-A inhibits ATP-primed exocytosis by blocking vesicle
      docking. Identification of blocking peptides which mimic sequences that bind to
      complementary partner domains on interacting proteins of the exocytotic machinery
      provides new pharmacological tools to dissect the molecular and mechanistic
      details of neurosecretion. Our findings may assist in developing ESUPs as
      substitute drugs to BoNTs for the treatment of spasmodic disorders.

PMID- 9006898
TI  - A novel hsp110-related gene, apg-1, that is abundantly expressed in the testis
      responds to a low temperature heat shock rather than the traditional elevated
      temperatures.
AB  - We isolated a novel hsp110-related gene, apg-1, from a testis cDNA library. The
      apg-1 transcripts were constitutively expressed in the testicular germ cells and,
      in some degree, most tissues examined. In a mouse TAMA26 Sertoli cell line, apg-1
      transcripts were induced in 2 h by a temperature shift from 32 to 39 degrees C,
      but not by a shift from 37 to 42 degrees C, the traditional heat stress, or a
      shift from 32 to 42 degrees C. The heat response pattern of hsp110 expression was
      similar to that of apg-1. Although induction of a hsp70 transcript was observed
      in 2 h by a shift from 32 to 39 degrees C, the induction was more apparent by a
      shift from 37 to 42 degrees C or from 32 to 42 degrees C. Essentially similar
      differential response patterns were observed among these genes in NIH/3T3
      fibroblasts as well. The nuclear run-on assay and the native gel mobility shift
      assay demonstrated that, by the 32 to 39 degrees C temperature shift, the apg-1
      gene was transcriptionally activated, and heat shock factor 1 bound to the heat
      shock elements in the 5'-flanking region of the apg-1 gene. These results
      demonstrated that expressions of apg-1, hsp110, and hsp70 could be heat-induced
      at a temperature lower than the traditional elevated temperatures in somatic
      cells of both testis and nontestis origin and suggest that the mechanisms
      regulating the transcript levels of apg-1 and hsp110 are different from those of
      hsp70. Furthermore, the constitutive expression in germ cells suggests that APG-1
      plays a specific role in spermatogenesis as well as in stress response.

PMID- 9006899
TI  - Differential activation of viral and cellular promoters by human T-cell
      lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms.
AB  - We have previously proposed that cAMP-responsive element-binding protein (CREB)
      activity is stimulated by human T-cell lymphotropic virus-1 (HTLV-1) Tax through
      two mechanisms that are differentially dependent upon CREB phosphorylation. We
      have tested this model by examining how Tax affects transcriptional activation
      mediated by the cAMP-responsive element (CRE) modulator (CREM). The CREM proteins
      are highly homologous to CREB, particularly in their DNA-binding domains and the
      kinase-inducible domain (KID), a region that interacts with the coactivator CREB
      binding protein (CBP) in a phosphorylation-dependent manner. Despite this
      similarity, most CREM isoforms are transcriptional repressors. CREMalpha lacks
      the glutamine-rich domains found in CREB that are essential for transcriptional
      activation. We show that the normally repressive CREMalpha activates the HTLV-1
      and cellular CREs in the presence of Tax; activation of the viral element is
      phosphorylation-independent, and activation of the cellular CRE is
      phosphorylation-dependent. CREMDelta(C-G) lacks both the KID and the glutamine
      rich regions. This isoform activates the HTLV-1 long terminal repeat in a
      phosphorylation-independent manner, but does not activate the cellular CRE. This
      study suggests that Tax, interacting with the basic/zipper region of CREM,
      recruits CBP to the viral promoter. Tax activation of the cellular CRE depends on
      the KID and its ability to interact with CBP in a phosphorylation-dependent
      manner.

PMID- 9006900
TI  - Identification of a chloroquine importer in Plasmodium falciparum. Differences in
      import kinetics are genetically linked with the chloroquine-resistant phenotype.
AB  - We demonstrate that uptake of the antimalarial drug chloroquine is temperature
      dependent, saturable, and inhibitable in Plasmodium falciparum. These features
      are indicative of carrier-mediated transport and suggest that a P. falciparum
      encoded protein facilitates chloroquine import. Although both chloroquine
      resistant and susceptible parasite isolates exhibit facilitated chloroquine
      uptake, the kinetics differ. Chloroquine-resistant parasite isolates consistently
      have an import mechanism with a lower transport activity and a reduced affinity
      for chloroquine. These differences in uptake kinetics are linked with chloroquine
      resistance in a genetic cross. These data suggest that changes in chloroquine
      import kinetics constitute a minimal and necessary event in the generation of the
      resistant phenotype. Competitive inhibition of chloroquine uptake by amiloride
      derivatives further suggests that chloroquine import is mediated by a plasmodial
      Na+/H+ exchanger.

PMID- 9006901
TI  - Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor
      binding protein with PH and SH2 domains.
AB  - cDNA clones encoding human (h) Grb7 and a previously unknown protein with high
      homology to hGrb-IR and mGrb10 (where m indicates mouse) were found by screening
      expressed sequence tag data bases. hGrb7 mRNA expression is greatest in pancreas
      and restricted to a few other tissues. The second protein termed hGrb
      IRbeta/Grb10 contains an intact PH domain and lacks the 80-residue mGrb10
      insertion. Expression is greatest in pancreas and muscle but occurs in nearly all
      tissues. hGrb-IRbeta/Grb10 and hGrb-IR likely arise as alternative mRNA splicing
      products of a common gene. Reverse transcriptase-coupled polymerase chain
      reaction shows both mRNAs in muscle. In cells, Grb-IRbeta/Grb10 protein
      translocates from cytosol to membrane upon insulin stimulation, most likely due
      to direct interactions with the insulin receptor. These interactions are mediated
      by the SH2 domain and additional regions of the protein. Studies with mutated
      receptors and synthetic phosphopeptides show that the hGrb-IRbeta/Grb10 SH2
      domain binds at least two sites in the insulin receptor: the kinase activation
      loop > the juxtamembrane site. hGrb-IRbeta/Grb10 also binds a 135-kDa
      phosphoprotein in unstimulated 3T3-L1 adipocytes; binding is reduced upon insulin
      stimulation. In addition, the c-Abl SH3 domain binds Grb-IR/Grb10, whereas Fyn,
      phosphatidylinositol 3-kinase p85, and Grb2 SH3 domains do not. The site of c-Abl
      SH3 domain interaction is highly conserved within the Grb-IR/Grb10/Grb7/Grb14
      family. hGrb-IRbeta/Grb10 also binds platelet-derived growth factor and epidermal
      growth factor receptors, suggesting a broader role in the signaling pathways of
      numerous receptors. We conclude that hGrb-IRbeta/Grb10 is a widely expressed, PH
      and SH2 domain-containing, SH3 domain-binding protein that functions downstream
      from activated insulin and growth factor receptors.

PMID- 9006903
TI  - Inositol 1,4,5-trisphosphate and calcium regulate the calcium channel function of
      the hepatic inositol 1,4,5-trisphosphate receptor.
AB  - The regulation of the inositol 1,4,5-trisphosphate (IP3) receptor in liver was
      analyzed using a novel superfusion method. Hepatic microsomes were loaded with
      45Ca2+, and superfused at high flow rates to provide precise control over IP3 and
      Ca2+ concentrations ([Ca2+]) and to isolate 45Ca2+ release from reuptake. 45Ca2+
      release was dependent on both [Ca2+] and IP3. The initial rate of 45Ca2+ release
      was a biphasic function of [Ca2+], increasing as [Ca2+] approached 3 microM but
      decreasing at higher concentrations, suggesting that the hepatic IP3 receptor is
      regulated by [Ca2+] at two sites, a high affinity potentiation site and a low
      affinity inhibitory site. The relationship between initial rates and IP3
      concentration was steep (Hill coefficient of 3.4), suggesting that activation of
      the calcium channel requires binding of at least 3 IP3 molecules. IP3
      concentrations above 10 microM produced rapid decay of release rates, suggesting
      receptor inactivation. Superfusion with 10 microM IP3 under conditions that
      minimize calcium release ([Ca2+] < 1 nM) inhibited 45Ca2+ release in response to
      subsequent stimulation (400 nM Ca2+). These data suggest sequential positive and
      negative regulation of the hepatic IP3 receptor by cytosolic calcium and by IP3,
      which may underlie hepatocellular propagation of regenerative, oscillatory
      calcium signals.

PMID- 9006902
TI  - Direct activation of the stress-activated protein kinase (SAPK) and extracellular
      signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated
      protein Kinase/ERK kinase kinase 3 (MEKK) derivative.
AB  - The extracellular signal-regulated kinase (ERK) pathway, the stress-activated
      protein kinase (SAPK) pathway, and the p38 pathway are three major mitogen
      activated protein kinase (MAPK) cascades known to participate in the regulation
      of cellular responses to a variety of extracellular signals. Upstream regulatory
      components of these kinase cascades, the MAPK/ERK kinase kinases (MEKK), have
      been described in several systems. We have isolated a cDNA encoding human MEKK3.
      Transfected MEKK3 has the ability to activate both SAPK and ERK pathways, but
      does not induce p38 activity, in agreement with a previous report on murine MEKK3
      (Blank, J. L., Gerwins, P., Elliott, E. M., Sather, S., and Johnson, G. L. (1996)
      J. Biol. Chem. 271, 5361-5368). We now demonstrate that MEKK3 activates SEK and
      MEK, the known kinases targeting SAPK and ERK, respectively. Utilizing an
      estrogen ligand-activated MEKK3 derivative, we furthermore demonstrate that MEKK3
      regulates the SAPK and the ERK pathway directly. Consistent with the fact that
      several SAPK-inducing agents activate the transcription factor NFkappaB, we now
      show that MEKK3 also enhances transcription from an NFkappaB-dependent reporter
      gene in cotransfection assays. The ability of MEKK3 to simultaneously activate
      the SAPK and ERK pathways is remarkable, given that they have divergent roles in
      cellular homeostasis.

PMID- 9006905
TI  - A casein kinase I activity is constitutively associated with Nck.
AB  - Nck is a 47-kDa cytosolic protein devoid of intrinsic catalytic activity and
      consisting of Src homology 2 and 3 (SH2 and SH3) domains organized as follows:
      SH3-SH3-SH3-SH2. Nck is believed to act as an adaptor protein mediating signal
      transduction initiated by receptor tyrosine kinases (RTKs). Through its SH2
      domain, Nck recognizes a specific phosphotyrosine residue on RTKs or on protein
      substrates of RTKs like insulin receptor substrate-1, the major substrate of the
      insulin receptor, and through its SH3 domains it interacts with poorly
      characterized effector molecules. To identify novel proteins that might interact
      with Nck, we have used the amino-terminal segment of Nck encompassing its three
      SH3 domains in the yeast two-hybrid system. Among the polypeptides that associate
      with Nck, we have identified the gamma2 isoform of the serine/threonine casein
      kinase I (CKI-gamma2). In transformed rat hepatocytes overexpressing the insulin
      receptor (HTC-IR cells), serine/threonine protein kinase activity
      coimmunoprecipitates with Nck, an interaction mediated mainly by the third SH3
      domain of Nck. This kinase activity is not apparently modulated by insulin, nor
      is it sensitive to staurosporine or heparin, and it does not use GTP as a
      phosphate donor. However the kinase activity coimmunoprecipitated with Nck is
      completely abolished by N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide, a
      specific inhibitor of casein kinase I. In an in vitro renaturation gel kinase
      assay, a protein kinase of 70-75 kDa was detected associated with the SH3 domains
      of Nck. Far Western analysis demonstrated that the SH3 domains of Nck bound
      directly to a cytosolic protein of 70-75 kDa. A rabbit polyclonal antibody raised
      against the C-terminal region of CKI-gamma2 protein kinase immunoprecipitated a
      single specific protein of 70-75 kDa from HTC-IR cell lysates and detected CKI
      gamma2 among the proteins coimmunoprecipitated with Nck. These results support an
      in vivo interaction between Nck and CKI-gamma2 and suggest that CKI-gamma2 could
      be involved in signaling pathways downstream of RTKs.

PMID- 9006904
TI  - Biosynthesis of the escherichia coli K4 capsule polysaccharide. A parallel system
      for studies of glycosyltransferases in chondroitin formation.
AB  - Escherichia coli K4 bacteria synthesize a capsule polysaccharide (GalNAc
      GlcA(fructose))n with the carbohydrate backbone identical to chondroitin. GlcA-
      and GalNAc-transferase activities from the bacterial membrane were assayed with
      acceptors derived from the capsule polysaccharide and radiolabeled UDP-[14C]GlcA
      and UDP-[3H]GalNAc, respectively. It was shown that defructosylated
      oligosaccharides (chondroitin) could serve as substrates for both the GlcA- and
      the GalNAc-transferases. The radiolabeled products were completely degraded with
      chondroitinase AC; the [14C]GlcA unit could be removed by beta-D-glucuronidase,
      and the [3H]GalNAc could be removed by beta-N-acetylhexosaminidase. A
      fructosylated oligosaccharide acceptor tested for GlcA-transferase activity was
      found to be inactive. These results indicate that the chain elongation reaction
      of the K4 polysaccharide proceeds in the same way as the polymerization of the
      chondroitin chain, by the addition of the monosaccharide units one by one to the
      nonreducing end of the polymer. This makes the biosynthesis of the K4
      polysaccharide an interesting parallel system for studies of chondroitin sulfate
      biosynthesis. In the biosynthesis of capsule polysaccharides from E. coli, a
      similar mechanism has earlier been demonstrated for polysialic acid (NeuNAc)n
      (Rohr, T. E., and Troy, F. A. (1980) J. Biol. Chem. 255, 2332-2342) and for the
      K5 polysaccharide (GlcAbeta1-4GlcNAcalpha1-4)n (Lidholt, K., Fjelstad, M., Jann,
      K., and Lindahl, U. (1994) Carbohydr. Res. 255, 87-101). In contrast, chain
      elongation of hyaluronan (GlcAbeta1-3GlcNAcbeta1-4)n is claimed to occur at the
      reducing end (Prehm, P. (1983) Biochem. J. 211, 181-189).

PMID- 9006906
TI  - ABC1, an ATP binding cassette transporter required for phagocytosis of apoptotic
      cells, generates a regulated anion flux after expression in Xenopus laevis
      oocytes.
AB  - The ATP binding cassette transporter ABC1 is a 220-kDa glycoprotein expressed by
      macrophages and required for engulfment of cells undergoing programmed cell
      death. Since members of this family of proteins such as P-glycoprotein and cystic
      fibrosis transmembrane conductance regulator share the ability to transport
      anions, we have investigated the transport capability of ABC1 expressed in
      Xenopus oocytes using iodide efflux and voltage-clamp techniques. We report here
      that ABC1 generates an anion flux sensitive to glibenclamide,
      sulfobromophthalein, and blockers of anion transporters. The anion flux generated
      by ABC1 is up-regulated by orthovanadate, cAMP, protein kinase A, and okadaic
      acid. In other ABC transporters, mutating the conserved lysine in the nucleotide
      binding folds was found to severely reduce or abolish hydrolysis of ATP, which in
      turn altered the activity of the transporter. In ABC1, replacement of the
      conserved lysine 1892 in the Walker A motif of the second nucleotide binding fold
      increased the basal ionic flux, did not alter the pharmacological inhibitory
      profile, but abolished the response to orthovanadate and cAMP agonists.
      Therefore, we conclude that ABC1 is a cAMP-dependent and sulfonylurea-sensitive
      anion transporter.

PMID- 9006907
TI  - Loss of GSH, oxidative stress, and decrease of intracellular pH as sequential
      steps in viral infection.
AB  - Madin-Darby canine kidney cells infected with Sendai virus rapidly lose GSH
      without increase in the oxidized products. The reduced tripeptide was
      quantitatively recovered in the culture medium of the cells. Since the GSH loss
      in infected cells was not blocked by methionine, a known inhibitor of hepatocyte
      GSH transport, a nonspecific leakage through the plasma membrane is proposed. UV
      irradiated Sendai virus gave the same results, confirming that the major loss of
      GSH was due to membrane perturbation upon virus fusion. Consequent to the loss of
      the tripeptide, an intracellular pH decrease occurred, which was due to a
      reversible impairment of the Na+/H+ antiporter, the main system responsible for
      maintaining unaltered pHi in those cells. At the end of the infection period, a
      rise in both pHi value and GSH content was observed, with a complete recovery in
      the activity of the antiporter. However, a secondary set up of oxidative stress
      was observed after 24 h from infection, which is the time necessary for virus
      budding from cells. In this case, the GSH decrease was partly due to preferential
      incorporation of the cysteine residue in the viral proteins and partly engaged in
      mixed disulfides with intracellular proteins. In conclusion, under our conditions
      of viral infection, oxidative stress is imposed by GSH depletion, occurring in
      two steps and following direct virus challenge of the cell membrane without the
      intervention of reactive oxygen species. These results provide a rationale for
      the reported, and often contradictory, mutual effects of GSH and viral infection.

PMID- 9006908
TI  - A bifunctionalized fluorogenic tetrasaccharide as a substrate to study
      cellulases.
AB  - Cellulases are usually classified as endoglucanases and cellobiohydrolases, but
      the heterogeneity of cellulose, in terms of particle size and crystallinity, has
      always represented a problem for the biochemical characterization of the enzymes.
      The synthesis of a bifunctionalized tetrasaccharide substrate suitable for
      measuring cellulase activity by resonance energy transfer is described. The
      substrate, which carries a 5-(2-aminoethylamino)-1-naphthalenesulfonate group on
      the non-reducing end and an indolethyl group on the reducing end, was prepared
      from beta-lactosyl fluoride and indolethyl beta-cellobioside by a chemoenzymatic
      approach using the transglycosylating activity of endoglucanase I of Humicola
      insolens as the key step. The bifunctionalized substrate has been used for the
      determination of the catalytic constants of H. insolens endoglucanase I and
      cellobiohydrolases I and II; this substrate could be of general use to measure
      the kinetic constants of cellulases able to act on oligomers of degree of
      polymerization <5. The data also provide evidence that cellobiohydrolases I and
      II are able to degrade an oligosaccharide substrate carrying non-carbohydrate
      substituents at both ends.

PMID- 9006909
TI  - Real time conformational changes in the retinal phosphodiesterase gamma subunit
      monitored by resonance energy transfer.
AB  - The gamma subunit of the retinal cGMP phosphodiesterase (gammaPDE) acts as an
      inhibitor of phosphodiesterase (PDE) catalytic activity and mediates enzyme
      regulation by the alpha subunit of the GTP-binding protein transducin (alphaT).
      In order to characterize conformational changes in the 87-amino acid gammaPDE
      subunit that may accompany the activation of the holoenzyme, gammaPDE was labeled
      with the fluorescent probes 5-iodoacetamidofluorescein and eosin-5-isothiocyanate
      for use in resonance energy transfer measurements. 5-Iodoacetamidofluorescein
      specifically labeled a cysteine residue at position 68 and served as a resonance
      energy transfer donor. The site of modification of eosin-5-isothiocyanate, which
      served as the resonance energy transfer acceptor, was determined to be within the
      first seven residues of the amino terminus of gammaPDE. Energy transfer between
      the labeled sites on free, unbound gammaPDE indicated that they were separated by
      a distance of 63 A, consistent with a random conformation. Upon binding the
      catalytic alphabeta subunits of the PDE, the distance between the two probes on
      gammaPDE increased to 77 A. Binding of the labeled gammaPDE by alphaT.guanosine
      5'-3-O-(thio)triphosphate did not affect the distance between the probes under
      conditions where the PDE was activated. These data are consistent with the view
      that the binding of activated alphaT to gammaPDE, which is essential for the
      stimulation of PDE activity, does not impart significant alterations in the
      tertiary structure of the gammaPDE molecule. They also support a model for PDE
      activation that places active alphaT in a complex with the holoenzyme.

PMID- 9006910
TI  - Identification of a retinoid/chicken ovalbumin upstream promoter transcription
      factor response element in the human retinoid X receptor gamma2 gene promoter.
AB  - To investigate the mechanisms involved in the transcriptional control of retinoid
      X receptor (RXR) gene expression, the 5'-flanking region of the human RXRgamma2
      isoform was characterized. An imperfect hexamer repeat (gamma retinoid X response
      element; gammaRXRE) with a single nucleotide spacer (GGTTGAaAGGTCA) was
      identified immediately upstream of the RXRgamma2 gene transcription start site.
      Cotransfection studies in CV-1 cells with expression vectors for the retinoid
      receptors RXRalpha and retinoic acid receptor beta (RARbeta) demonstrated that
      the gammaRXRE confers retinoid-mediated transcriptional activation with
      preferential activation by RXR in the presence of its cognate ligand, 9-cis
      retinoic acid (RA). Electrophoretic mobility shift assays demonstrated that RXR
      homodimer binding to gammaRXRE is markedly enhanced by 9-cis-RA, whereas RAR.RXR
      heterodimer binding is ligand-independent. DNA binding studies and cell
      cotransfection experiments also demonstrated that the nuclear receptor, chicken
      ovalbumin upstream promoter transcription factor (COUP-TF), repressed
      transcription via the gammaRXRE. Cotransfection experiments revealed that COUP-TF
      and RXRalpha compete at the gammaRXRE to modulate transcription bidirectionally
      over a wide range. These results demonstrate that the human RXRgamma2 gene
      promoter contains a novel imperfect repeat element capable of mediating RXR
      dependent transcriptional autoactivation and COUP-TF-dependent repression.

PMID- 9006911
TI  - The filamentous fungus Aspergillus niger contains two "differentially regulated"
      trehalose-6-phosphate synthase-encoding genes, tpsA and tpsB.
AB  - Two genes encoding trehalose-6-phosphate synthase were cloned from Aspergillus
      niger. tpsA was cloned using the Saccharomyces cerevisiae GGS1/TPS1 gene as a
      probe. It encodes a 517-amino acid polypeptide with 64-70% similarity to
      trehalose-6-phosphate synthase of S. cerevisiae, Kluyveromyces lactis, and
      Schizosaccharomyces pombe. Its transcription occurs constitutively and is
      enhanced on carbon-derepressing carbon sources, coinciding with the presence of a
      CreA-binding nucleotide motif in the 5'-noncoding region of tpsA. Disruption of
      tpsA only weakly reduces growth on glucose, and neither influences the glucose
      induction of a low affinity glucose permease nor interferes with the catabolite
      repression of a pectinase; it causes reduced the heat tolerance of conidia. tpsB
      was cloned by a polymerase chain reaction-based strategy. Its 480 amino acid
      sequence showed 76.5% identity to tpsA. Its transcription was hardly detectable
      at ambient temperatures but was enhanced strongly upon heat shock, which agrees
      with the presence of several copies of a C4T stress-responsive element in its 5'
      upstream sequences. Hence the function of yeast GGS1/TPS1 has been split into two
      differentially regulated genes in A. niger, of which none appears to be involved
      in glucose sensing.

PMID- 9006912
TI  - Ligation of integrin alpha5beta1 is required for internalization of vitronectin
      by integrin alphavbeta3.
AB  - Remodeling of the matrix by tumor cells is necessary for tumor invasion. We have
      shown previously that malignant astrocytomas, in contrast to normal astrocytes,
      synthesize vitronectin and express integrins alphavbeta3 and alphavbeta5. The
      activity states of these two integrins are differentially controlled. Thus, we
      investigated the regulation of the activity of integrins alphavbeta3 and
      alphavbeta5 with regard to their role in vitronectin internalization in U-251MG
      astrocytoma cell monolayers adherent to fibronectin, collagen, or laminin in
      serum-free conditions. Binding of [125I]vitronectin occurred in a specific,
      saturable manner that was partially inhibitable by monoclonal antibodies (mAbs)
      specific for integrins alphavbeta3 or alphavbeta5. Specific, lysosomally-mediated
      degradation of [125I]vitronectin was detectable at 1 h and increased over the 24
      h assay period. The cell substrate affected the rate of turnover of
      [125I]vitronectin, which was 3.0 ng/min for cells plated on fibronectin but 0.35
      ng/min for cells plated on collagen. Furthermore, although mAbs specific for
      either integrin alphavbeta3 or alphavbeta5 inhibited degradation (30%; combined
      effect 70%) of [125I]vitronectin by cells plated on fibronectin, only mAb anti
      alphavbeta5 inhibited degradation (70-90%) by cells plated on collagen or
      laminin. To determine the requirement for integrin alpha5beta1 ligation in order
      for integrin alphavbeta3 to internalize its ligand, cells were plated on mAbs
      anti-integrin alpha5 or anti-integrin alpha3. When plated on mAb anti-alpha5,
      mAbs anti-alphavbeta3 and anti-alphavbeta5 both inhibited degradation. However,
      when plated on mAb anti-alpha3, mAb anti-alphavbeta3 had no effect whereas mAb
      anti-alphavbeta5 inhibited degradation. These data indicate that a signal from
      integrin alpha5beta1 is necessary for integrin alphavbeta3 to internalize
      vitronectin, whereas integrin alphavbeta5 constitutively internalizes
      vitronectin.

PMID- 9006913
TI  - Siroheme biosynthesis in higher plants. Analysis of an S-adenosyl-L-methionine
      dependent uroporphyrinogen III methyltransferase from Arabidopsis thaliana.
AB  - Siroheme, the prosthetic group for both nitrite and sulfite reductases, is a
      methylated, iron-containing modified tetrapyrrole. Here we report the first
      molecular characterization of the branch point enzyme in higher plants, which
      directs intermediates toward siroheme synthesis. A cDNA was cloned from
      Arabidopsis thaliana (UPM1) that functionally complements an Escherichia coli
      cysG mutant, a strain that is unable to catalyze the conversion of
      uroporphyrinogen III (Uro'gen-III) to siroheme. UPM1 is 1484 base pairs and
      encodes a 369-amino acid, 39.9-kDa protein. The UPM1 product contains two regions
      that are identical to consensus sequences found in bacterial Uro'gen-III and
      precorrin methyltransferases. Recombinant UPM1 protein was found to catalyze S
      adenosyl-L-methionine-dependent transmethylation by UPM1 in a multistep process
      involving the formation of a covalently linked complex with S-adenosyl-L
      methionine. The UPM1 product has a sequence at the amino terminus that resembles
      a transit peptide for localization to mitochondria or plastids. The protein
      produced by in vitro expression is able to enter isolated intact chloroplasts but
      not mitochondria. Genomic blot analysis showed that UPM1 is encoded in the A.
      thaliana genome. The genomic DNA corresponding to UPM1 was cloned and sequenced
      and found to contain at least five introns.

PMID- 9006914
TI  - Tumor necrosis factor alpha-induced E-selectin expression is activated by the
      nuclear factor-kappaB and c-JUN N-terminal kinase/p38 mitogen-activated protein
      kinase pathways.
AB  - E-selectin expression by endothelium is crucial for leukocyte recruitment during
      inflammatory responses. Transcriptional regulation of the E-selectin promoter by
      tumor necrosis factor alpha (TNFalpha) requires multiple nuclear factor-kappaB
      (NF-kappaB) binding sites and a cAMP-responsive element/activating transcription
      factor-like binding site designated positive domain II (PDII). Here we
      characterize the role of the stress-activated family of mitogen-activated protein
      (MAP) kinases in induced expression of this adhesion molecule. By UV cross
      linking and immunoprecipitation, we demonstrated that a heterodimer of
      transcription factors ATF-2 and c-JUN is constitutively bound to the PDII site.
      TNFalpha stimulation of endothelial cells induces transient phosphorylation of
      both ATF-2 and c-JUN and induces marked activation of the c-JUN N-terminal kinase
      (JNK1) and p38 but not extracellular signal-regulated kinase (ERK1). JNK and p38
      are constitutively present in the nucleus, and DNA-bound c-JUN and ATF-2 are
      stably contacted by JNK and p38, respectively. MAP/ERK kinase kinase 1 (MEKK1),
      an upstream activator of MAP kinases, increases E-selectin promoter transcription
      and requires an intact PDII site for maximal induction. MEKK1 can also activate
      NF-kappaB -dependent gene expression. The effects of dominant interfering forms
      of the JNK/p38 signaling pathway demonstrate that activation of these kinases is
      critical for cytokine-induced E-selectin gene expression. Thus, TNFalpha
      activates two signaling pathways, NF-kappaB and JNK/p38, which are both required
      for maximal expression of E-selectin.

PMID- 9006915
TI  - A benzo[a]pyrene-induced cell cycle checkpoint resulting in p53-independent G1
      arrest in 3T3 fibroblasts.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor of
      the basic helix-loop-helix family. Although physiological ligands for the AhR
      have not been identified, carcinogenic polycyclic aromatic hydrocarbons such as
      Benzo[a]pyrene (B[a]P) are high affinity AhR ligands that induce nuclear
      translocation and sequence-specific DNA binding of the AhR. AhR-regulated genes
      include members of the cytochrome P-450 family that are known to oxidize B[a]P to
      form genotoxic (DNA-damaging) metabolites. Murine Swiss 3T3 cells express high
      levels of AhR. Treatment of Swiss 3T3 cells with B[a]P during the G1 phase of the
      cell cycle resulted in growth arrest, as shown by inhibition of growth factor
      stimulated DNA synthesis. By contrast, other murine 3T3 fibroblasts not
      expressing detectable levels of AhR did not undergo growth arrest in response to
      B[a]P. The AhR antagonist alpha-naphthoflavone prevented B[a]P-induced growth
      arrest, further demonstrating that cessation of cell growth was mediated by the
      activated AhR. A nongenotoxic AhR ligand (2,3,7,8-tetrachlorodibenzo-p-dioxin)
      did not elicit growth arrest, showing that ligand activation of the AhR alone was
      insufficient to block cell cycle progression. However, genomic DNA from B[a]P
      treated Swiss 3T3 cells contained covalent adducts, whereas that from 2,3,7,8
      tetrachlorodibenzo-p-dioxin-treated cells did not, showing that G1 arrest
      correlated with DNA damage resulting from genotoxic B[a]P metabolites. B[a]P
      induced DNA damage and growth arrest was coincident with elevated levels of
      nuclear p53 protein and induction of the p53-regulated mdm-2 proto-oncogene.
      However, Swiss 3T3 fibroblasts expressing "dominant negative" mutant p53, as well
      as primary fibroblasts from p53-/- "knockout" mice, also underwent growth arrest
      in response to B[a]P. Therefore, B[a]P-induced growth arrest occurs via p53
      independent mechanisms.

PMID- 9006916
TI  - Protein disulfide isomerase and newly synthesized procollagen chains form higher
      order structures in the lumen of the endoplasmic reticulum.
AB  - A number of proteins that act as necessary catalysts for correct protein folding
      and oligomerization in the endoplasmic reticulum (ER) are known to be retained in
      the organelle via the KDEL-receptor mediated retrieval mechanism. However, a
      complementary system that may help to retain these proteins in the organelle
      lumen has been suggested to exist and likely involves physical protein-protein
      interactions at the level of endoplasmic reticulum (ER) itself. In this report,
      we provide both morphological and biochemical evidence in support of this
      proposal. We show that in collagen-secreting human skin fibroblasts, protein
      disulfide isomerase and newly synthesized procollagen chains exist predominantly
      in an "aggregated" state, and form a reticular-like matrix in the ER lumen in
      vivo. The size of the aggregates was found to be variable, and may exceed 1.5
      million Da. Aggregate formation appeared to be transient and to involve multiple
      types of protein-protein interactions, including formation of aberrant disulfide
      bonds. Association of protein disulfide isomerase, on the other hand, was found
      to require at least partly function-related disulfide bonds. These results
      support the existence of a reticular-like matrix in the ER lumen, and suggest
      that aggregation may be part of the normal maturation pathway during collagen
      biosynthesis.

PMID- 9006917
TI  - Early emergence of three dopamine D1 receptor subtypes in vertebrates. Molecular
      phylogenetic, pharmacological, and functional criteria defining D1A, D1B, and D1C
      receptors in European eel Anguilla anguilla.
AB  - The existence of dopamine D1C and D1D receptors in Xenopus and chicken,
      respectively, challenged the established duality (D1A and D1B) of the dopamine D1
      receptor class in vertebrates. To ascertain the molecular diversity of this gene
      family in early diverging vertebrates, we isolated four receptor-encoding
      sequences from the European eel Anguilla anguilla. Molecular phylogeny assigned
      two receptor sequences (D1A1 and D1A2) to the D1A subtype, and a third receptor
      to the D1B subtype. Additional sequence was orthologous to the Xenopus D1C
      receptor and to several other previously unclassified fish D1-like receptors.
      When expressed in COS-7 cells, eel D1A and D1B receptors display affinity
      profiles for dopaminergic ligands similar to those of other known vertebrate
      homologues. The D1C receptor exhibits pharmacological characteristics virtually
      identical to its Xenopus homologue. Functionally, while all eel D1 receptors
      stimulate adenylate cyclase, the eel D1B receptor exhibits greater constitutive
      activity than either D1A or D1C receptors. Semiquantitative reverse transcription
      polymerase chain reaction reveals the differential distribution of D1A1, D1A2,
      D1B, and D1C receptor mRNA within the hypothalamic-pituitary axis of the eel
      brain. Taken together, these data suggest that the D1A, D1B, and D1C receptors
      arose prior to the evolutionary divergence of fish and tetrapods and exhibit
      molecular, pharmacological, and functional attributes that unambiguously allow
      for their classification as distinct D1 receptor subtypes in the vertebrate
      phylum.

PMID- 9006919
TI  - On the inhibition mechanism of sarcoplasmic or endoplasmic reticulum Ca2+-ATPases
      by cyclopiazonic acid.
AB  - Ca2+-ATPase inhibition by stoichiometric and substoichiometric concentrations of
      cyclopiazonic acid was studied in sarcoplasmic reticulum preparations from rabbit
      fast-twitch muscle. The apparent affinity of the nonphosphorylated enzyme for ATP
      showed a Kd of approximately 3 microM in the absence of cyclopiazonic acid and
      approximately 28 microM in the presence of the drug. Fractional saturation of the
      enzyme by cyclopiazonic acid was accompanied by the appearance of two ATP-binding
      populations (enzyme with and without drug) and a progressive increase in the half
      maximal concentration for saturating the ATP-binding sites. Enzyme turnover in
      the presence of stoichiometric concentrations of cyclopiazonic acid displayed
      lower apparent affinity for ATP and lower maximal hydrolytic activity than in the
      absence of the drug. When cyclopiazonic acid is in the substoichiometric range,
      the observed kinetic parameters will correspond to the simultaneous contribution
      of two different reaction cycles sustained by the enzyme with and without drug.
      The inhibition could be elicited by adding ATP to allow the enzyme turnover when
      cyclopiazonic acid was preincubated with the enzyme in the presence of Ca2+. The
      onset of inhibition during enzyme cycling was observed over a period of seconds,
      revealing the existence of a low inhibition rate constant. It is concluded that
      cyclopiazonic acid decreases enzyme affinity for ATP in non-turnover conditions
      by approximately one order of magnitude. This allows enzyme cycling after drug
      binding, provided that a high ATP concentration is used. Cyclopiazonic acid and
      ATP do not compete for the same binding site.

PMID- 9006918
TI  - Regulated exocytosis in chromaffin cells. A potential role for a secretory
      granule-associated ARF6 protein.
AB  - The ADP-ribosylation factor (ARF) GTP-binding proteins are believed to function
      as regulators of vesicular budding and fusion along the secretory pathway. To
      investigate the role of ARF in regulated exocytosis, we have examined its
      intracellular distribution in cultured chromaffin cells by subcellular
      fractionation and immunoreplica analysis. We found that ARF6 is specifically
      associated with the membrane of purified secretory chromaffin granules. Chemical
      cross-linking and immunoprecipitation experiments suggested that ARF6 may be part
      of a complex with betagamma subunits of trimeric G proteins. Stimulation of
      intact chromaffin cells or direct elevation of cytosolic calcium in permeabilized
      cells triggered the rapid dissociation of ARF6 from secretory granules. This
      effect could be inhibited by AlF4- which selectively activates trimeric G
      proteins. Furthermore, a synthetic myristoylated peptide corresponding to the N
      terminal domain of ARF6 strongly inhibited calcium-evoked secretion in
      streptolysin-O-permeabilized chromaffin cells. The possibility that ARF6 plays a
      role in the effector pathway by which trimeric G proteins control exocytosis in
      chromaffin cells is discussed.

PMID- 9006920
TI  - An Alu-linked repetitive sequence corresponding to 280 amino acids is expressed
      in a novel bovine protein, but not in its human homologue.
AB  - A novel protein harboring a 280-amino acid region from an Alu-linked repetitive
      sequence (bovine Alu-like dimer-driven family) was isolated from a bovine brain S
      100 fraction using monoclonal antibodies against a rat GTPase-activating protein
      that shares the same epitope. The protein has an apparent molecular mass of 97
      kDa (p97). Western blot analysis using extracts prepared from various tissues
      showed p97 to be predominantly detected in brain and moderately in liver and
      lung. From sequence analysis of the cDNA encoding p97, it was found that the 840
      base pair sequence homologous to a part of the bovine Alu-like dimer-driven
      family, which has never been shown to be expressed, occurs in the middle of the
      protein coding region. The protein also contains a pair of intramolecular repeats
      composed of 40 highly hydrophilic amino acids at the C terminus. Human cDNA
      homologous to p97 was cloned, and its nucleotide sequence demonstrates that the
      840-base pair repetitive sequence and one of the intramolecular repeats are
      missing. We named p97 bovine BCNT after Bucentaur. These results show that bovine
      BCNT is a unique molecule and suggest that an analysis of the relationship
      between bovine bcnt and its human homologue may help further the understanding of
      gene organization and evolution.

PMID- 9006921
TI  - The early stage of chloroplast protein import involves Com70.
AB  - The chloroplast envelope protein Com70 is a hsp70 homolog identified recently as
      a component of the protein translocation apparatus. The stage of protein import
      involving Com70 was determined by examining the nature of the association of
      Com70 with the envelope and its interaction with translocating proteins. Com70 is
      accessible to thermolysin, but its association with the envelope could not be
      disrupted by stringent washes. In light of the external membrane-bound location,
      the involvement of Com70 at the early stage of protein translocation was
      investigated using a combination of in vitro binding assays, chemical cross
      linking, and coimmunoprecipitation. The results provide evidence that Com70 is in
      close physical proximity to different types of chloroplast protein precursors
      under conditions supporting binding rather than complete translocation. The
      formation of cross-linked complexes is dependent on the presence of a typical
      plastid transit signal and protease-accessible outer envelope components. The
      close proximity of Com70 and the translocating protein occurs while the protein
      is still exposed to the cytosol.

PMID- 9006922
TI  - Fibulin-2 binds to the short arms of laminin-5 and laminin-1 via conserved amino
      acid sequences.
AB  - Epithelial cell-specific laminin-5, consisting of three chains, alpha3, beta3,
      and gamma2, is a component of the anchoring filament that traverses the lamina
      lucida beneath the hemidesmosomes of epidermal cells and functions to link these
      cells to the basement membrane. We have studied the molecular interaction between
      laminin-5 and extracellular matrix proteins using recombinant proteins and
      synthetic peptides. Affinity chromatography assays with recombinant fragments of
      the laminin gamma2 short arm identified a 195-kDa binding protein in the
      conditioned media from the mouse epidermal cell line Pam 212 and from primary
      dermal fibroblasts. This molecule was identified by Western blotting as fibulin
      2, a recently identified extracellular matrix protein. Using deletion mutants and
      various synthetic peptides in competition assays, the 9-amino acid sequence
      SADFSVHKI (residues 199-207) in domain IV of the gamma2 chain was defined as a
      critical site for fibulin-2 binding. An anti-gamma2 antibody co
      immunoprecipitated fibulin-2 from the conditioned media, further confirming the
      interaction of fibulin-2 with laminin-5. Fibulin-2 was also found to interact
      with laminin-1 (alpha1beta1gamma1) through a region (residues 654-665) of the
      alpha1 chain short arm whose sequence is similar to that of the fibulin-2 binding
      site of the gamma2 chain. Together these results suggest that fibulin-2 functions
      to bridge laminin-1 and laminin-5 with other extracellular matrix proteins,
      providing a linkage between the cell surface and the basement membrane.

PMID- 9006923
TI  - Binding of the Brucella abortus lipopolysaccharide O-chain fragment to a
      monoclonal antibody. Quantitative analysis by fluorescence quenching and
      polarization.
AB  - An antigenic O-chain polysaccharide fragment derived from Brucella abortus
      lipopolysaccharide was labeled with 14.8 +/- 1.8 (n = 5) and 52.3 +/- 2.4 (n = 3)
      micromol of fluorescein/g of polysaccharide (designated FL1 and FL2,
      respectively) for use in investigating the binding of O-chain to a specific
      murine antibody YsT9 under equilibrium conditions. Upon binding to YsT9, the
      fluorescence of FL1 and FL2 was quenched 45-57% with no shift in the excitation
      and emission spectra, and polarization of fluorescence increased by 300-335%.
      With fluorescence quenching and polarization as sensitive signals for antibody
      bound labeled O-chains, the equilibrium constants for binding of FL1, FL2, and
      unlabeled O-chain to YsT9 were determined to be within a similar order (1.5 x
      10(7) to 2.0 x 10(7) M-1) using a nonlinear curve fitting approach rather than
      Scatchard analysis. These results indicated that covalent attachment of
      fluorescein groups to the O-chain did not influence the recognition of the YsT9
      defined epitope by the antibody. The reversibility of the O-chain-antibody
      reaction was also demonstrated by showing a rapid depolarization of the labeled O
      chain-antibody complex in the presence of unlabeled O-chain, suggesting that this
      displacement experiment could be exploited to quantify the Brucella
      polysaccharide antigen. The study described here provides a useful model for
      characterization of the complex formation between a carbohydrate-binding protein
      and a carbohydrate ligand and also for the design of a homogeneous assay system
      to quantitate antigens or antibodies of clinical interest.

PMID- 9006924
TI  - Interaction of GM2 activator protein with glycosphingolipids.
AB  - GM2 activator protein is a protein cofactor that has been shown to stimulate the
      enzymatic hydrolysis of both GalNAc and NeuAc from GM2 (Wu, Y. Y., Lockyer, J.
      M., Sugiyama, E., Pavlova, N.V., Li, Y.-T., and Li, S.-C. (1994) J. Biol. Chem.
      269, 16276-16283). To understand the mechanism by which GM2 activator stimulates
      the hydrolysis of GM2, we examined the interaction of this activator protein with
      GM2 as well as with other glycosphingolipids by TLC overlay and Sephacryl S-200
      gel filtration. The TLC overlay analysis unveiled the binding specificity of GM2
      activator, which was not previously revealed. Under the conditions optimal for
      the activator protein to stimulate the hydrolysis of GM2 by beta-hexosaminidase
      A, GM2 activator was found to bind avidly to acidic glycosphingolipids, including
      gangliosides and sulfated glycosphingolipids, but not to neutral
      glycosphingolipids. The gangliosides devoid of sialic acids, such as asialo-GM1
      and asialo-GM2, and the GM2 derivatives whose carboxyl function in the NeuAc had
      been modified by methyl esterification or reduction, were only very weakly bound
      to GM2 activator. These results indicate that the negatively charged sugar
      residue or sulfate group in gangliosides is one of the important sites recognized
      by GM2 activator. For comparison, we also studied in parallel the complex
      formation between glycosphingolipids and saposin B, a separate activator protein
      with broad specificity to stimulate the hydrolysis of various glycosphingolipids.
      We found that saposin B bound to neutral glycosphingolipids and gangliosides
      equally well, and there was an exceptionally strong binding to sulfatide. In
      contrast to previous reports, we found that GM2 activator formed complexes with
      GM2 and other gangliosides in different proportions depending on the ratio
      between the activator protein and the ganglioside in the incubation mixture prior
      to gel filtration. We were not able to detect the specific binding of GM2
      activator to GM2 when GM2 was mixed with GM1 or GM3. Thus, the specificity or the
      mode of action of GM2 activator cannot be simply explained by its interaction
      with glycosphingolipids based on complex formation. The binding of GM2 activator
      to a wide variety of negatively charged glycosphingolipids may indicate that this
      activator protein has functions other than assisting the enzymatic hydrolysis of
      GM2.

PMID- 9006925
TI  - Overexpression, purification, and characterization of the catalase-peroxidase
      KatG from Mycobacterium tuberculosis.
AB  - Wild-type catalase-peroxidase KatG from Mycobacterium tuberculosis as well as a
      specific mutant (R463L) frequently found in isoniazid-resistant strains have been
      overexpressed in Escherichia coli, allowing purification of sufficient quantities
      of enzyme for physical and kinetic characterization. Optical absorption and EPR
      spectroscopies indicate that KatG is similar to a growing class of bacterial
      catalase-peroxidases. Optical and EPR spectra of KatG in the presence of either a
      strong field or weak field ligand suggest that, like horseradish peroxidase and
      metmyoglobin, KatG is likely to have a histidine as a proximal ligand. The wild
      type enzyme functions as a highly active catalase as well as a broad specificity
      peroxidase. Wild-type KatG and the R463L mutant of KatG exhibit identical
      spectroscopic and kinetic properties. Furthermore, both enzymes are equally
      capable of metabolizing the important antituberculosis drug isoniazid.

PMID- 9006926
TI  - A novel reaction mechanism for the formation of S-nitrosothiol in vivo.
AB  - The objective of this study was to investigate the mechanism of S-nitrosothiol
      formation under physiological conditions. A mechanism is proposed by which nitric
      oxide (.NO) reacts directly with reduced thiol to produce a radical intermediate,
      R-S-N.-O-H. This intermediate reduces an electron acceptor to produce S
      nitrosothiol. Under aerobic conditions O2 acts as the electron acceptor and is
      reduced to produce superoxide (O-2). The following experimental evidence is
      provided in support of this mechanism. Cysteine accelerates the consumption of
      .NO by 2.5-fold under physiological conditions. The consumption of O2 in the
      presence of .NO and cysteine is increased by 2.4-fold. The reaction orders of .NO
      and cysteine are second and first order, respectively. The second order of
      reaction for .NO may result from interaction between .NO and O-2 to form
      peroxynitrite. In the presence of Cu,Zn-superoxide dismutase, the reaction of .NO
      with cysteine generates hydrogen peroxide, indicating that the reaction generates
      O-2. Finally, the formation of S-nitrosothiol is demonstrated in an anaerobic
      environment and, as predicted by the mechanism, is dependent on the presence of
      an electron acceptor. These results demonstrate that under physiological
      conditions .NO reacts directly with thiols to form S-nitrosothiol in the presence
      of an electron acceptor.

PMID- 9006927
TI  - Effect of growth factors on the expression of 6-phosphofructo-2-kinase/fructose
      2,6-bisphosphatase in Rat-1 fibroblasts.
AB  - The activation of glycolytic flux is a biochemical characteristic of growing
      cells. Several reports have demonstrated the role of fructose 2,6-bisphosphate in
      this process. In this paper we show that the levels of 6-phosphofructo-2
      kinase/fructose-2, 6-bisphosphatase (6PF2K/Fru-2,6-P2ase) mRNA are modulated in
      response to serum and growth factors and this effect is due to regulation of its
      transcription rate. The modulation of the expression of this enzyme by growth
      factors differs according their mitogenic effect; both lysophosphatidic acid and
      epidermal growth factor, when added alone, increased the mRNA levels, but
      endothelin had no effect. Furthermore, cAMP, which acts as an antimitogenic
      signal in Rat-1 fibroblasts, produced a decrease in 6PF2K/Fru-2, 6-P2ase mRNA and
      inhibited the effects of lysophosphatidic acid and epidermal growth factor on
      6PF2K/Fru-2,6-P2ase expression. PD 098059, a specific inhibitor of the activation
      of the mitogen-activated protein kinase, was able to prevent the effect of EGF on
      6PF2K/Fru-2, 6-P2ase gene expression. These results imply that activation of
      mitogen-activated protein kinase is required for the stimulation of the
      transcription of 6PF2K/Fru-2,6-P2ase by EGF.

PMID- 9006928
TI  - Comparison of the effects of phospholamban and jasmone on the calcium pump of
      cardiac sarcoplasmic reticulum. Evidence for modulation by phospholamban of both
      Ca2+ affinity and Vmax (Ca) of calcium transport.
AB  - Regulation of the calcium pump of the cardiac sarcoplasmic reticulum by
      phosphorylation/dephosphorylation of phospholamban is central to the inotropic
      and lusitropic effects of beta-adrenergic agonists on the heart. In order to
      study the mechanism of this regulation, we first obtained purified ruthenium red
      insensitive microsomes enriched in sarcoplasmic reticulum membranes. The kinetics
      of microsomal Ca2+ uptake after phospholamban phosphorylation or trypsin
      treatment, which cleaves the inhibitory cytoplasmic domain of phospholamban, were
      then compared with those in the presence of jasmone, whose effects on the
      kinetics of fast skeletal muscle Ca2+-ATPase are largely known. All three
      treatments increased Vmax (Ca) at 25 degrees C and millimolar ATP;
      phosphorylation and trypsin decreased the Km (Ca), while jasmone increased it.
      Trypsin and jasmone increased the rate of E2P decomposition 1.8- and 3. 0-fold,
      respectively. The effects of phospholamban phosphorylation and jasmone on the
      Ca2+-ATPase activity paralleled their effects on Ca2+ uptake. Our data
      demonstrate that phospholamban regulates E2P decomposition in addition to the
      known increase in the rate of a conformational change in the Ca2+-ATPase upon
      binding the first of two Ca2+. These steps in the catalytic cycle of the Ca2+
      ATPase may contribute to or account for phospholamban's effects on both Vmax (Ca)
      and Km (Ca), whose relative magnitude may vary under different experimental and,
      presumably, physiological conditions.

PMID- 9006929
TI  - Regulation of T4 phage aerobic ribonucleotide reductase. Simultaneous assay of
      the four activities.
AB  - We have devised an assay procedure that permits simultaneous monitoring of the
      four activities of ribonucleotide reductase. Using this assay, we have compared
      the reduction of all four substrates by the T4 bacteriophage aerobic
      ribonucleotide reductase within different allosteric environments. Specifically,
      we compared the relative turnover rates by the enzyme when activated with "in
      vivo" concentrations of the known allosteric effectors versus activation by ATP
      alone. Consistent with the known allosteric properties of this enzyme, our
      results show that ATP does act as a general activator, although the rate of
      purine nucleotide reduction was approximately 5% of the rate for the pyrimidine
      nucleotides. However, addition of the allosteric effectors at their estimated
      physiological concentrations dramatically changed the relative rates of substrate
      reduction, creating a more "balanced" pool of products. Addition of the
      substrates at their respective in vivo concentrations further pushed rates of
      product formation toward a ratio similar to the base composition of the T4
      genome. The similarity of the product profile produced under in vivo conditions
      to the genomic composition of T4 phage is discussed.

PMID- 9006930
TI  - Bisecting GlcNAc structures act as negative sorting signals for cell surface
      glycoproteins in forskolin-treated rat hepatoma cells.
AB  - The bisecting N-acetylglucosamine residue is formed by UDP-N
      acetylglucosamine:beta-D-mannoside-beta-1, 4-N-acetylglucosaminyltransferase III
      (GnT-III), a key branching enzyme for N-glycans. We found that forskolin, an
      adenylyl cyclase activator, markedly enhanced GnT-III at the transcriptional
      level in various hepatoma cells and hepatocytes, resulting in an increase of
      bisecting GlcNAc residues in various glycoproteins, as judged from the lectin
      binding to erythroagglutinating phytohemagglutinin (E-PHA). In whole cell
      lysates, the E-PHA binding was increased, and leukoagglutinating
      phytohemagglutinin (L-PHA) binding was decreased at 12 h after forskolin
      treatment, by time, both GnT-III activity and mRNA had reached the maximum
      levels. In contrast, the binding capacity as to E-PHA, determined by fluorescence
      activated cell sorting on the cell surface, was decreased, suggesting that
      bisecting GlcNAc structures in certain glycoproteins changed the expression
      levels of glycoproteins and decreased their sorting on the cell surface.
      Fractionated organelles of M31 cells showed that the binding capacity as to E-PHA
      was mainly localized in Golgi membranes and lysosomes. This was also supported by
      a fluorescence microscopy. In order to determine whether or not the bisecting
      GlcNAc residue acts as a sorting signal for glycoproteins, N-oligosaccharide
      structures of lysosomal-associated membrane glycoprotein 1 and beta
      glucuronidase, gamma-glutamyltranspeptidase, and secretory glycoproteins such as
      ceruloplasmin and alpha-fetoprotein were measured by E-PHA and L-PHA blotting
      after immunoprecipitation. The expression levels of lysosomal membrane
      glycoprotein 1 and gamma-glutamyltranspeptidase on the cell surface were
      decreased at 12 h after forskolin treatment, indicating that the bisecting GlcNAc
      structure may act as a negative sorting signal for the cell surface glycoproteins
      and may alter the characteristics of hepatoma cells. This is the first report on
      glycoprotein sorting related to a specific structure of oligosaccharides,
      bisecting GlcNAc.

PMID- 9006932
TI  - Receptor-induced internalization of selective peptidic mu and delta opioid
      ligands.
AB  - The binding and internalization of radioiodinated and fluorescent mu and delta
      opioid peptides in mammalian cells were quantitatively studied by biochemical
      techniques and directly visualized by confocal microscopy. The labeled peptides
      were prepared by inserting either a 125I-Bolton-Hunter group or a fluorescent
      probe into the C-terminal part of 5-aminopentylamide derivatives of deltorphin-I
      and [Lys7]dermorphin. The purified derivatives kept most of their specificity and
      selectivity toward delta and mu opioid receptors, respectively. Biochemical and
      confocal microscopy data showed that both mu and delta opioid peptides were
      internalized in mammalian cells transfected with the corresponding opioid
      receptor according to a receptor-mediated mechanism. The internalization process
      was time- and temperature-dependent and was completely blocked by the endocytosis
      inhibitor phenylarsine oxyde. Internalization of both delta and mu ligands
      occurred from a single large cap at one pole of the cell, indicating that
      polymerization of ligand-receptor complexes preceeded internalization. Finally,
      green and red fluorescent analogues of deltorphin-I and [Lys7]dermorphin,
      respectively, were found to internalize through partly distinct endocytic
      pathways in cells co-transfected with mu and delta receptors, suggesting that
      each of these receptors interacts with distinct proteins mediating intracellular
      sorting and trafficking.

PMID- 9006931
TI  - cDNA cloning, genomic organization, and in vivo expression of rat N-syndecan.
AB  - The amino acid sequence of rat N-syndecan core protein was deduced from the
      cloned cDNA sequence. The sequence predicts a core protein of 442 amino acids
      with six structural domains: an NH2-terminal signal peptide, a membrane distal
      glycosaminoglycan attachment domain, a mucin homology domain, a membrane proximal
      glycosaminoglycan attachment domain, a single transmembrane domain, and a
      noncatalytic COOH-terminal cytoplasmic domain. Transfection of human 293 cells
      resulted in the expression of N-syndecan that was modified by heparan sulfate
      chain addition. Heparitinase digestion of the expressed proteoglycan produced a
      core protein that migrated on SDS-polyacrylamide gels at an apparent molecular
      weight of 120, 000, identical to N-syndecan synthesized by neonatal rat brain or
      Schwann cells. Rat genomic DNA coding for N-syndecan was isolated by
      hybridization screening. The rat N-syndecan gene is comprised of five exons. Each
      exon corresponds to a specific core protein structural domain, with the exception
      of the fifth exon, which contains the coding information for both the
      transmembrane and cytoplasmic domains as well as the 3'-untranslated region of
      the mRNA. The first intron is large, with a length of 22 kilobases. The
      expression of N-syndecan was investigated in late embryonic, neonatal, and adult
      rats by immunoblotting and Northern blotting analysis. Among the tissues and
      developmental stages studied, high levels of N-syndecan expression were
      restricted to the early postnatal nervous system. N-syndecan was expressed in all
      regions of the nervous system, including cortex, midbrain, spinal cord, and
      peripheral nerve. Immunohistochemical staining revealed high levels of N-syndecan
      expression in all brain regions and fiber tract areas.

PMID- 9006933
TI  - A single residue substitution causes a switch from the dual DNA binding
      specificity of plant transcription factor MYB.Ph3 to the animal c-MYB
      specificity.
AB  - Transcription factor MYB.Ph3 from Petunia binds to two types of sequences, MBSI
      and MBSII, whereas murine c-MYB only binds to MBSI, and Am305 from Antirrhinum
      only binds to MBSII. DNA binding studies with hybrids of these proteins pointed
      to the N-terminal repeat (R2) as the most involved in determining binding to MBSI
      and/or MBSII, although some influence of the C-terminal repeat (R3) was also
      evident. Furthermore, a single residue substitution (Leu71 --> Glu) in MYB.Ph3
      changed its specificity to that of c-MYB, and c-MYB with the reciprocal
      substitution (Glu132 --> Leu) essentially gained the MYB.Ph3 specificity.
      Molecular modeling and DNA binding studies with site-specific MYB.Ph3 mutants
      strongly supported the notion that the drastic changes in DNA binding specificity
      caused by the Leu --> Glu substitution reflect the fact that certain residues
      influence this property both directly, through base contacts, and indirectly,
      through interactions with other base-contacting residues, and that a single
      residue may establish alternative base contacts in different targets.
      Additionally, differential effects of mutations at non-base-contacting residues
      in MYB.Ph3 and c-MYB were observed, reflecting the importance of protein context
      on DNA binding properties of MYB proteins.

PMID- 9006934
TI  - Identification of Smad2, a human Mad-related protein in the transforming growth
      factor beta signaling pathway.
AB  - Transforming growth factor-beta (TGF-beta) superfamily members are
      multifunctional cytokines that exert their effects via heteromeric complexes of
      two distinct serine and threonine kinase receptors. Drosophila mothers against
      decapentaplegic and related genes in Caenorhabditis elegans, Xenopus, and mammals
      were shown to function downstream in the intracellular signaling pathways of TGF
      beta superfamily members. Here we report the cloning of a Mad-related protein,
      termed Sma- and Mad-related protein 2 (Smad2). TGF-beta stimulated the
      phosphorylation and nuclear translocation of Smad2 in nontransfected Mv1Lu cells.
      In addition, we demonstrated that TGF-beta and activin mediated phosphorylation
      of Smad2 after its overexpression with appropriate type I and II receptors in COS
      cells. Smad2 and Smad1 were found to be broadly expressed in human tissues. Smad2
      is closely linked to DPC4 on chromosome 18q21.1, a region often deleted in human
      cancers. Cells that lack Smad2 may escape from TGF-beta-mediated growth
      inhibition and promote cancer progression.

PMID- 9006936
TI  - Identification of the region in actin-binding protein that binds to the
      cytoplasmic domain of glycoprotein IBalpha.
AB  - Actin-binding protein (ABP-280) is a component of the submembranous cytoskeleton
      and interacts with the glycoprotein (GP) Ibalpha subunit of the GP Ib-IX complex
      in platelets. In the present studies, we have identified the binding site for GP
      Ibalpha in ABP-280. A melanoma cell line lacking ABP-280 was stably transfected
      with the cDNAs coding for GP Ib-IX, then transiently transfected with cDNA coding
      for various carboxyl-truncates of ABP-280. Immunocapture assays and co
      immunoprecipitation experiments from detergent-lysed cells showed that deletion
      of the carboxyl-terminal repeats 20-24 of ABP-280 had no effect on GP Ib-IX
      binding, but deletion of residues 2099 through 2136 within repeat 19 abolished
      binding. In the yeast two-hybrid system, an ABP-280 fragment comprising repeats
      17-19 bound GP Ibalpha. Deletion from either end abolished binding. Individual or
      multiple repeats of ABP-280 were expressed as fusion protein in bacteria and
      purified; structural folding was evaluated, and binding to GP Ib-IX was assessed.
      Binding depended on the presence of repeats 17-19. None of the individual repeats
      were able to bind to GP Ib-IX. These findings demonstrate that residues 1850-2136
      comprising repeats 17-19 contain the binding site for GP Ib-IX.

PMID- 9006935
TI  - Sp1 is a critical regulator of the Wilms' tumor-1 gene.
AB  - We performed deletion analysis of WT1-reporter constructs containing up to 24
      kilobases of 5'-flanking and first intron WT1 sequence in stably transfected
      cultured cells as an unbiased approach to identify cis elements critical for WT1
      transcription. Although not a tissue-specific element, a proximate 9-base pair
      CTC repeat accounted for approximately 80% of WT1 transcription in this assay.
      Enhancer activity of the element and mutated versions correlated completely with
      their ability to form a DNA-protein complex in gel shifts. Antibody supershift,
      oligonucleotide competition, and Southwestern studies indicated that the CTC
      binding factor is the transcriptional activator Sp1. Sp1 binds the CTC repeat
      with an affinity, KD = 0.37 nM, at least as high as the consensus GC box. Similar
      CTC repeats are found in promoters of other growth-related genes. Because Sp1 is
      important for WT1 expression, we examined Sp1 immunohistochemistry in fetal and
      adult kidney. In a pattern that precedes that of WT1 message, Sp1 immunostaining
      was highest in uninduced mesenchyme, early tubules, developing podocytes, and
      mature glomeruli, but was minimal in mature proximal tubules. This work suggests
      abundant Sp1 may be a prerequisite for WT1 expression, and that Sp1 may have a
      wider role in nephrogenesis.

PMID- 9006937
TI  - Identification of two amino acids of the human cholecystokinin-A receptor that
      interact with the N-terminal moiety of cholecystokinin.
AB  - A region between residues 38 and 42 of the human cholecystokinin-A (CCK-A)
      receptor was shown to be involved in the binding of CCK but not in that of JMV
      179 and JMV 180, two peptides closely related to CCK (Kennedy, K., Escrieut, C.,
      Dufresne, M., Clerc, P., Vaysse, N., and Fourmy, D. (1995) Biochem. Biophys. Res.
      Commun. 213, 845-852). In the present study, we have identified the residues of
      both the receptor and the ligand responsible for this differential binding.
      Residues Trp-39 and Gln-40 of the receptor were crucial for binding of the C
      terminal nonapeptide of CCK as W39F and Q40N mutants demonstrated parallel
      decreases in both affinity and potency to induce accumulation of inositol
      phosphates (12.9- and 20.9-fold). The W39F and Q40N mutant receptors bound CCK
      analogues modified at their C-terminal end, including JMV 179 and JMV 180, as
      well as the C-terminal amidated heptapeptide of CCK, with identical affinities to
      the wild-type receptor. In contrast, W39F and Q40N mutants bound CCK octapeptide
      with the same decreased affinity as the CCK nonapeptide. The modeling of the CCK
      A receptor and the docking of the peptide agonists [Thr,Nle]CCK9 and CCK-8
      indicated that their N terminus was connected to the receptor through a strong
      bond network involving Trp-39 and Gln-40 thus confirming experimental data. These
      first molecular data identifying the agonist binding site of the human CCK-A
      receptor represent an important step toward the complete delineation of the
      agonist binding site and the understanding of the molecular mechanisms that
      govern differential activation of this receptor by CCK-related peptides.

PMID- 9006938
TI  - The enhanced tumorigenic activity of a mutant epidermal growth factor receptor
      common in human cancers is mediated by threshold levels of constitutive tyrosine
      phosphorylation and unattenuated signaling.
AB  - Deregulation of signaling by the epidermal growth factor receptor (EGFR) is
      common in human malignancy progression. One mutant EGFR (variously named
      DeltaEGFR, de2-7 EGFR, or EGFRvIII), which occurs frequently in human cancers,
      lacks a portion of the extracellular ligand-binding domain due to genomic
      deletions that eliminate exons 2 to 7 and confers a dramatic enhancement of brain
      tumor cell tumorigenicity in vivo. In order to dissect the molecular mechanisms
      of this activity, we analyzed location, autophosphorylation, and attenuation of
      the mutant receptors. The mutant receptors were expressed on the cell surface and
      constitutively autophosphorylated at a significantly decreased level compared
      with wild-type EGFR activated by ligand treatment. Unlike wild-type EGFR, the
      constitutively active DeltaEGFR were not down-regulated, suggesting that the
      altered conformation of the mutant did not result in exposure of receptor
      sequence motifs required for endocytosis and lysosomal sorting. Mutational
      analysis showed that the enhanced tumorigenicity was dependent on intrinsic
      tyrosine kinase activity and was mediated through the carboxyl terminus. In
      contrast with wild-type receptor, mutation of any major tyrosine
      autophosphorylation site abolished these activities suggesting that the
      biological functions of DeltaEGFR are due to low constitutive activation with
      mitogenic effects amplified by failure to attenuate signaling by receptor down
      regulation.

PMID- 9006939
TI  - Cloning and expression of a novel mammalian thioredoxin.
AB  - We have isolated a 1276-base pair cDNA from a rat heart cDNA library that encodes
      a novel thioredoxin (Trx2) of 166 amino acid residues with a calculated molecular
      mass of 18.2 kDa. Trx2 possesses the conserved thioredoxin-active site, Trp-Cys
      Gly-Pro-Cys, but lacks structural cysteines present in all mammalian
      thioredoxins. Trx2 also differs from the previously described rat thioredoxin
      (Trx1) by the presence of a 60-amino acid extension at the N terminus. This
      extension has properties characteristic for a mitochondrial translocation signal,
      and the cleavage at a putative mitochondrial peptidase cleavage site would give a
      mature protein of 12.2 kDa. Western blot analysis from cytosolic, peroxisomal,
      and mitochondrial rat liver cell fractions confirmed mitochondrial localization
      of Trx2. Northern blot and reverse transcriptase-polymerase chain reaction
      analyses revealed that Trx2 hybridized to a 1.3-kilobase message, and it was
      expressed in several tissues with the highest expression levels in heart, muscle,
      kidney, and adrenal gland. N-terminally truncated recombinant protein was
      expressed in bacteria and characterized biochemically. Trx2 possessed a dithiol
      reducing enzymatic activity and, with mammalian thioredoxin reductase and NADPH,
      was able to reduce the interchain disulfide bridges of insulin. Furthermore, Trx2
      was more resistant to oxidation than Trx1.

PMID- 9006940
TI  - Key residues in subsite F play a critical role in the activity of Pseudomonas
      fluorescens subspecies cellulosa xylanase A against xylooligosaccharides but not
      against highly polymeric substrates such as xylan.
AB  - In a previous study crystals of Pseudomonas fluorescens subspecies cellulosa
      xylanase A (XYLA) containing xylopentaose revealed that the terminal nonreducing
      end glycosidic bond of the oligosaccharide was adjacent to the catalytic residues
      of the enzyme, suggesting that the xylanase may have an exo-mode of action.
      However, a cluster of conserved residues in the substrate binding cleft indicated
      the presence of an additional subsite, designated subsite F. Analysis of the
      biochemical properties of XYLA revealed that the enzyme was a typical endo
      beta1,4-xylanase, providing support for the existence of subsite F. The three
      dimensional structure of four family 10 xylanases, including XYLA, revealed
      several highly conserved residues that are on the surface of the active site
      cleft. To investigate the role of some of these residues, appropriate mutations
      of XYLA were constructed, and the biochemical properties of the mutated enzymes
      were evaluated. N182A hydrolyzed xylotetraose to approximately equal molar
      quantities of xylotriose, xylobiose, and xylose, while native XYLA cleaved the
      substrate to primarily xylobiose. These data suggest that N182 is located at the
      C site of the enzyme. N126A and K47A were less active against xylan and aryl-beta
      glycosides than native XYLA. The potential roles of Asn-126 and Lys-47 in the
      function of the catalytic residues are discussed. E43A and N44A, which are
      located in the F subsite of XYLA, retained full activity against xylan but were
      significantly less active than the native enzyme against oligosaccharides smaller
      than xyloseptaose. These data suggest that the primary role of the F subsite of
      XYLA is to prevent small oligosaccharides from forming nonproductive enzyme
      substrate complexes.

PMID- 9006941
TI  - FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens.
AB  - Engagement of CD95 or tumor necrosis factor 1 receptor (TNFR-1) by ligand or
      agonist antibodies is capable of activating the cell death program, the effector
      arm of which is composed of mammalian interleukin-1beta converting enzyme (ICE)
      like cysteine proteases (designated caspases) that are related to the
      Caenorhabditis elegans death gene, CED-3. Caspases, unlike other mammalian
      cysteine proteases, cleave their substrates following aspartate residues.
      Furthermore, proteases belonging to this family exist as zymogens that in turn
      require cleavage at internal aspartate residues to generate the two-subunit
      active enzyme. As such, family members are capable of activating each other.
      Remarkably, both CD95 and TNFR-1 death receptors initiate apoptosis by recruiting
      a novel ICE/CED-3 family member, designated FLICE/MACH, to the receptor signaling
      complex. Therefore, FLICE/MACH represents the apical triggering protease in the
      cascade. Consistent with this, recombinant FLICE was found capable of
      proteolytically activating downstream caspases. Furthermore, CrmA, a pox virus
      encoded serpin that inhibits Fas and tumor necrosis factor-induced cell death
      attenuates the ability of FLICE to activate downstream caspases.

PMID- 9006942
TI  - Phosphorylation of protein-tyrosine phosphatase PTP-1B on identical sites
      suggests activation of a common signaling pathway during mitosis and stress
      response in mammalian cells.
AB  - PTP-1B is a widely expressed non-transmembrane tyrosine-specific phosphatase.
      Previous studies indicated that, at mitosis, PTP-1B undergoes phosphorylation on
      two sites, 352Ser-Pro-Leu-Asn and 386Ser-Pro-Ala-Lys. Although the Ser-386 site
      can be phosphorylated by Cyclin B/Cdc2 in vitro, the kinase for the Ser-352 site
      is unknown. We have found that these phosphorylation events are not unique to
      normal mitosis. Instead, treatment with many, but not all, stress stimuli, in
      particular osmotic shock and certain phosphatase and protein synthesis
      inhibitors, leads to phosphorylation of PTP-1B. Tryptic phosphopeptide and mutant
      analysis reveals that, as in mitosis, stress-induced PTP-1B phosphorylation
      involves both Ser-352 and Ser-386. Activation of the proline-directed kinases
      Erk1/2, JNKs, and p38 was neither necessary nor sufficient for stress-induced PTP
      1B phosphorylation. Our data suggest the existence of a novel mitogen-activated
      protein kinase pathway in mammalian cells, which is activated at mitosis and in
      response to osmotic shock and other stresses and results in PTP-1B
      phosphorylation. This pathway may be similar to the recently described Spc1/Sty1
      pathway in Schizosaccharomyces pombe.

PMID- 9006943
TI  - Distinct multisite synergistic interactions determine substrate specificities of
      human chymase and rat chymase-1 for angiotensin II formation and degradation.
AB  - Human chymase and rat chymase-1 are mast cell serine proteases involved in
      angiotensin II (Ang II) formation and degradation, respectively. Previous studies
      indicate that both these enzymes have similar P1 and P2 preferences, which are
      the major determinants of specificity. Surprisingly, despite the occurrence of
      optimal P2 and P1 residues at the Phe8 downward arrow and Tyr4 downward arrow
      bonds (where downward arrow, indicates the scissile bond in peptide substrates)
      in Ang I (DRVYIHPFHL), human chymase cleaves the Phe8 downward arrow bond with an
      approximately 750-fold higher catalytic efficiency (kcat/Km) than the Tyr4
      downward arrow bond in Ang II (DRVYIHPF), whereas rat chymase-1 cleaves the Tyr4
      downward arrow bond with an approximately 20-fold higher catalytic efficiency
      than the Phe8 downward arrow bond. Differences in the acyl groups IHPF and DRVY
      at the Phe8 downward arrow and Tyr4 downward arrow bonds, respectively, are
      chiefly responsible for the preference of human chymase for the Phe8 downward
      arrow bond. We show that the IHPF sequence forms an optimal acyl group, primarily
      through synergistic interactions between neighboring acyl group residues. In
      contrast to human chymase, rat chymase-1 shows a preference for the Tyr4 downward
      arrow bond, mainly because of a catalytically productive interaction between the
      enzyme and the P'1 Ile5. The overall effect of this P'1 Ile interaction on
      catalytic efficiency, however, is influenced by the structure of the acyl group
      and that of the other leaving group residues. For human chymase, the P'1 Ile
      interaction is not productive. Thus, specificity for Ang II formation versus Ang
      II degradation by these chymases is produced through synergistic interactions
      between acyl or leaving group residues as well as between the acyl and leaving
      groups. These observations indicate that nonadditive interactions between the
      extended substrate binding site of human chymase or rat chymase-1 and the
      substrate are best explained if the entire binding site is taken as an entity
      rather than as a collection of distinct subsites.

PMID- 9006944
TI  - Selective reporter expression in mast cells using a chymase promoter.
AB  - Primate alpha-chymases are mast cell neutral proteases that are involved in
      regulating several regulatory peptides including angiotensin II. Because of
      significant substrate specificity differences among the chymase group of enzymes,
      animal models that overexpress primate chymases are crucial for delineating the
      in vivo function of these enzymes. Activation of alpha-prochymase requires
      processing enzymes and proteoglycans found in mast cell secretory granules. Thus,
      the development of models overexpressing active primate chymase requires a mast
      cell-specific promoter. We show that the 571-base pair (bp) 5'-upstream sequence
      of the baboon chymase gene, which encodes an alpha-chymase, coupled to the
      prokaryotic lacZ gene allows the targeting of beta-galactosidase to mast cells in
      transgenic mice. Tissue expression of the transgene is similar to the expression
      of the endogenous mouse alpha-chymase mouse mast cell protease-5. A mouse mast
      cell line that endogenously expresses mouse mast cell protease-5 (JKras mast
      cells) also selectively supports the expression of this transgene. In vitro
      transcription studies in JKras mast cells shows the critical role of a GATA cis
      regulatory motif in baboon chymase promoter, located approximately 430-bp
      upstream of the transcription start site. These results suggest that the 571-bp
      domain of the baboon chymase promoter contains most, if not all, of the mast cell
      specific region of the promoter. We describe here for the first time a promoter
      that directs expression of transgenes specifically to mouse mast cells. This
      promoter should be generally applicable for dominant expression of mast cell
      regulatory proteins.

PMID- 9006945
TI  - Identification of alpha-spectrin domains susceptible to ubiquitination.
AB  - Previously, we demonstrated that alpha-spectrin is a substrate for the ubiquitin
      system and that this conjugation is a dynamic process (Corsi, D., Galluzzi, L.,
      Crinelli, R., and Magnani, M. (1995) J. Biol. Chem. 270, 8928-8935). In this
      study, we mapped the sites of ubiquitination on erythrocyte alpha-spectrin. A
      peptide map of digested alpha-spectrin, previously submitted to in vitro 125I
      ubiquitin conjugation, revealed the presence of four distinct labeled bands with
      Mr 40,000, 36,000, 29,000, and 25,500. Western blotting experiments using
      antibodies against each alpha-spectrin domain revealed that only IgG anti
      alphaIII domain recognized the 125I-labeled ubiquitin peptide of 29 kDa, whereas
      the IgG anti-alphaV domain recognized the Mr 40,000 125I-ubiquitin-labeled
      peptide. The other two labeled bands of Mr 36,000 and Mr 25,500 were identified
      as tetra and tri multiubiquitin chains. Ubiquitination of the alphaIII and alphaV
      domains was further confirmed by anti-alpha-spectrin domain immunoaffinity
      chromatography. Endoprotease Lys C-digested spectrin conjugated previously to
      125I-ubiquitin was incubated with antibodies against each trypsin-resistant
      domain of alpha-spectrin. Gamma counting of the radiolabeled antigen-antibody
      complexes purified by protein A chromatography showed labeling in the IgG anti
      alphaIII and anti-alphaV complexes alone. Domain alphaIII is not associated with
      any known function, whereas domain alphaV contains the nucleation site for the
      association of the alpha and beta chains. Ubiquitination of the latter domain
      suggests a role for ubiquitin in the modulation of the stability, deformability,
      and viscoelastic properties of the erythrocyte membrane.

PMID- 9006946
TI  - The retinoblastoma interacting zinc finger gene RIZ produces a PR domain-lacking
      product through an internal promoter.
AB  - The PR domain is a newly recognized protein motif that characterizes a subfamily
      of Kruppel-like zinc finger genes. Members of the PR domain family have been
      shown to play important roles in cell differentiation and malignant
      transformation. The RIZ gene is the founding member of this family; it was
      isolated because its gene products can bind to the retinoblastoma tumor
      suppressor protein. Here, we have studied the RIZ gene structure and expression.
      By immunoprecipitation and immunoblot analysis we identified two different RIZ
      protein products of 280 and 250 kDa, designated RIZ1 and RIZ2, respectively. The
      280-kDa RIZ1 product comigrated with the RIZ cDNA-derived polypeptide. The 250
      kDa RIZ2 product lacked the NH2-terminal PR domain of RIZ1; it comigrated with a
      truncated RIZ1 polypeptide that was initiated from an internal ATG codon. Both
      the full-length and the truncated RIZ1 polypeptide were located in the nucleus as
      shown by transfection and immunofluorescence analysis. We identified the RIZ2
      transcripts and showed that they were produced by an internal promoter located at
      the 5' boundary of coding exon 5. RNase protection analysis revealed similar
      ratios of RIZ1 and RIZ2 transcripts in most adult rat tissues except in testis,
      where RIZ1 was more abundant than RIZ2. These observations were strikingly
      similar to those described for the MDS1-EVI1 cancer gene, which also normally
      gives rise to a PR domain-lacking product, EVI1, because of an internal promoter.

PMID- 9006947
TI  - Trematode myoglobins, functional molecules with a distal tyrosine.
AB  - The myoglobins of two trematodes, Paramphistomum epiclitum and Isoparorchis
      hypselobagri, were isolated to homogeneity. The native molecules are monomeric
      with Mr 16,000-17,000 and pI 6.5-7.5. In each species, at least four different
      globin isoforms occur. Primary structure was determined at the protein level. The
      globin chains contain 147 amino acid residues. Although major determinants of the
      globin fold are conserved, characteristic substitutions are present. A Tyr
      residue occurs at the helical positions B10 and E7 (distal position). This is
      confirmed by NMR measurements (Zhang, W., Rashid, K. A., Haque, M., Siddiqi, A.
      H., Vinogradov, S. N., Moens, L. & La Mar, G. N. (1997) J. Biol. Chem. 272, 3000
      3006). A distal Tyr normally provokes oxidation of the iron atom and the
      inability to bind oxygen, whereas a Tyr-B10 is indicative for a high oxygen
      affinity. In contrast, trematode myoglobins are functional molecules with a high
      oxygen affinity. Molecular modeling predicts two possible positions for the
      aromatic ring of Tyr-E7: one being outside the heme pocket making it freely
      accessible to the ligand and one within the heme pocket potentially able to form
      a second hydrogen bond with the iron-bound oxygen. A hydrogen bond between Tyr
      B10 and the bound oxygen as in the Ascaris hemoglobin is predicted as well. The
      predicted structure may explain the high oxygen affinity of the trematode
      myoglobins.

PMID- 9006948
TI  - Solution of 1H NMR structure of the heme cavity in the oxygen-avid myoglobin from
      the trematode Paramphistomum epiclitum.
AB  - A two-dimensional 1H NMR study has been carried out on the heme cavity of the
      extreme oxygen-avid and autoxidation-resistant oxy-myoglobin complex from the
      trematode Paramphistomum epiclitum, and the residues were identified which
      potentially provide hydrogen bond stabilization for the bound oxygen. Complete
      assignment of the heme core resonances allows the identification of 10 key heme
      pocket residues, 4 Phe, 4 Tyr, and 2 upfield ring current aliphatic side chains.
      Based solely on the conserved myoglobin folding topology that places the E helix
      heme crossover and the completely conserved Phe(CD1)-heme contact at opposing
      meso positions, the heme orientation in the cavity and the E helix alignment were
      unambiguously established that place Tyr66 at position E7. Moreover, all eight
      aromatic and the two aliphatic side chains were shown to occupy the positions in
      the heme cavity predicted by amino acid sequence alignment with globins of known
      tertiary structure. The dipolar contacts for the Tyr32(B10) and Tyr66(E7) rings
      indicate that both residues are oriented into the heme cavity, which is
      unprecedented in globins. The ring hydroxyl protons for both Tyr are close to
      each other and in a position to provide hydrogen bonds to the coordinated oxygen,
      as supported by strong retardation of their exchange rate with bulk solvent. A
      more crowded and compact structure increases the dynamic stability of the distal
      pocket and may contribute to the autoxidation resistance of this myoglobin.

PMID- 9006949
TI  - Quaternary associations of acetylcholinesterase. I. Oligomeric associations of T
      subunits with and without the amino-terminal domain of the collagen tail.
AB  - We investigated the production of acetylcholinesterase of type T (AChET) in COS
      cells during transient transfection. When expressed alone, Torpedo AChET remains
      essentially intracellular, forming dimers and tetramers; in contrast, rat AChET
      is secreted and produces mostly amphiphilic monomers (G1a) and dimers (G2a),
      together with smaller proportions of nonamphiphilic (G4na) tetramers, amphiphilic
      tetramers (G4a), and an unstable higher polymer (13.7 S). The latter two forms
      have not been described before. We show that secreted G1a and G2a forms differ
      from their cellular counterparts and that proteolytic cleavage occurs at the COOH
      terminus of "flagged" subunits. The binding proteins QN/HC and QN/stop are
      constructed by associating the NH2-terminal domain of the collagen tail (QN) with
      a functional or truncated signal for addition of a glycolipidic anchor
      (glycophosphatidylinositol). Coexpression with QN/stop recruits monomers and
      dimers to form soluble tetramers (G4na), increasing the yield of secreted rat
      AChE and allowing secretion of Torpedo AChE. Using antibodies against QN or
      addition of a flag epitope, we showed that the secreted tetramers contain the
      attachment domain. Coexpression with QN/HC modifies the distribution of AChET in
      subcellular compartments and allows the externalization of
      glycophosphatidylinositol-anchored tetramers at the cell surface.

PMID- 9006950
TI  - Quaternary associations of acetylcholinesterase. II. The polyproline attachment
      domain of the collagen tail.
AB  - In transfected COS cells, we analyzed the formation of heteromeric associations
      between rat acetylcholinesterase of type T (AChET) and various constructions
      derived from the NH2-terminal region of the collagen tail of asymmetric forms,
      QN. Using a series of deletions and point mutations in QN, we showed that the
      binding of AChET to QN does not require the cysteines that normally establish
      intersubunit disulfide bonds with catalytic subunits and that it essentially
      relies on the presence of stretches of successive prolines, although adjacent
      residues also contribute to the interaction. We thus defined a proline-rich
      attachment domain or PRAD, which recruits AChET subunits to form heteromeric
      associations. Such molecules, consisting of one PRAD associated with a tetramer
      of AChET, are exported efficiently by the cells. Using the proportion of AChET
      subunits engaged in heteromeric tetramers, we ranked the interaction efficiency
      of various constructions. From these experiments we evaluated the contribution of
      different elements of the PRAD to the quaternary assembly of AChET subunits in
      the secretory pathway. The PRAD remained functional when reduced to six residues
      followed by a string of 10 prolines (Glu-Ser-Thr-Gly3-Pro10). We then showed that
      synthetic polyproline itself can associate with AChET subunits, producing well
      defined tetramers, when added to live transfected cells or even to cell extracts.
      This is the first example of an in vitro assembly of AChE tetramers from monomers
      and dimers. These results open the way to a chemical-physical exploration of the
      formation of these quaternary associations, both in the secretory pathway and in
      vitro.

PMID- 9006951
TI  - Potassium channel alpha and beta subunits assemble in the endoplasmic reticulum.
AB  - We have characterized the maturation of Shaker K+ channel protein and the
      cellular site of assembly of pore-forming alpha and cytoplasmic beta subunits in
      a transfected mammalian cell line. Shaker protein is made as a partially
      glycosylated, immature precursor that is converted to a fully glycosylated,
      mature product. Shaker protein did not mature when transport from the endoplasmic
      reticulum (ER) to the Golgi apparatus was blocked. Consistent with this finding,
      only the immature form was sensitive to digestion with endoglycosidase H. These
      results indicate that the immature protein is core-glycosylated in the ER,
      whereas the oligosaccharides of the mature protein have been further processed in
      the Golgi compartment. After inhibiting ER-to-Golgi transport, the oligomeric
      state of Shaker subunits was assessed by cross-linking in intact cells or by
      solubilization and sucrose gradient sedimentation. The results indicate that
      Shaker subunits assemble with each other in the ER. When co-expressed, the
      Kvbeta2 subunit also associated with Shaker in the ER. Assembly with the beta2
      subunit did not increase the rate or extent of Shaker protein maturation. Our
      results indicate that the biogenesis of Shaker K+ channels in vivo involves core
      glycosylation and subunit assembly in the ER, followed by efficient transfer to
      the Golgi apparatus where the oligosaccharides are modified.

PMID- 9006952
TI  - Elevation of ceramide within distal neurites inhibits neurite growth in cultured
      rat sympathetic neurons.
AB  - Sphingolipids are abundant constituents of neuronal membranes and have been
      implicated in intracellular signaling. We show that two analogs of
      glycosphingolipid biosynthetic intermediates, fumonisin B1 (which inhibits
      dihydroceramide synthesis) and DL-1-phenyl-2-palmitoylamino-3-morpholino-1
      propanol (PPMP) (which inhibits glucosylceramide synthesis) decrease
      glycosphingolipid synthesis in rat sympathetic neurons. Although both fumonisin
      and PPMP inhibit glycosphingolipid synthesis, these inhibitors have differential
      effects on ceramide metabolism in axons. threo-PPMP, but not erythro-PPMP or
      fumonisin, induces an accumulation of [3H]palmitate-labeled ceramide and impairs
      axonal growth. Moreover, exogenously added, cell-permeable C6-ceramide, but not
      C6-dihydroceramide, mimicks the effect of PPMP. Our studies suggest that the
      lipid second messenger ceramide acts in distal axons, but not cell bodies, as a
      negative regulator of neurite growth.

PMID- 9006953
TI  - Substrate-binding lipoprotein of the cyanobacterium Synechococcus sp. strain PCC
      7942 involved in the transport of nitrate and nitrite.
AB  - Of the four genes (nrtABCD) required for active transport of nitrate in the
      cyanobacterium Synechococcus sp. strain PCC 7942, nrtBCD encode membrane
      components of an ATP-binding cassette transporter involved in the transport of
      nitrite as well as of nitrate, whereas nrtA encodes a 45-kDa cytoplasmic membrane
      protein, the biochemical function of which remains unclear. Characterization of
      the nrtA deletional mutants showed that the 45-kDa protein is essential for the
      functioning of the nitrate/nitrite transporter. A truncated NrtA protein lacking
      the N-terminal 81 amino acids, expressed in Escherichia coli cells as a histidine
      tagged soluble protein, was shown to bind nitrate and nitrite with high affinity
      (Kd = 0.3 microM). Immunoblotting analysis using the antibody against the 45-kDa
      protein revealed a 48-kDa precursor of the protein, which accumulated in the
      cyanobacterial cells treated with globomycin, an antibiotic that specifically
      inhibits cleavage of the signal peptide of lipoprotein precursors. These findings
      indicated that the nrtA gene product is a nitrate- and nitrite-binding
      lipoprotein. The N-terminal sequences of putative cyanobacterial substrate
      binding proteins suggested that lipoprotein modification of substrate-binding
      proteins of ATP-binding cassette transporters is common in cyanobacteria.

PMID- 9006954
TI  - Characterization of a secretory type Theileria parva glutaredoxin homologue
      identified by novel screening procedure.
AB  - The schizont stage of the protozoan parasite Theileria parva induces features
      characteristic of tumor cells in infected bovine T-cell lines. Most strikingly T.
      parva-infected cell lines acquire unlimited growth potential in vitro. Their
      proliferative state is entirely dependent on the presence of a viable parasite
      within the host cell cytoplasm. It has been postulated that parasite proteins
      either secreted into the host cell or expressed on the parasite surface membrane
      are involved in the parasite-host cell interaction. We used an in vitro
      transcription-translation-membrane translocation system to identify T. parva
      derived cDNA clones encoding secretory or membrane proteins. Within 600 clones we
      found one encoding a 17-kDa protein which is processed by microsomal membranes to
      a 14-kDa protein (11E), presumably by signal peptidase. The processed form is
      expressed in the T-cell line TpM803 harboring viable parasites. By
      immunolocalization we show that the 11E protein mostly resides within the
      parasite, often in close vicinity to membranous structures, but in addition it
      appears at the surface membrane. Amino acid sequence comparison suggests that 11E
      belongs to the glutaredoxin family, but is unique so far in containing a signal
      sequence for endoplasmic reticulum membrane translocation.

PMID- 9006955
TI  - Identification of a putative mitochondrial telomere-binding protein of the yeast
      Candida parapsilosis.
AB  - Terminal segments (telomeres) of linear mitochondrial DNA (mtDNA) molecules of
      the yeast Candida parapsilosis consist of large sequence units repeated in
      tandem. The extreme ends of mtDNA terminate with a 5' single-stranded overhang of
      about 110 nucleotides. We identified and purified a mitochondrial telomere
      binding protein (mtTBP) that specifically recognizes a synthetic oligonucleotide
      derived from the extreme end of this linear mtDNA. MtTBP is highly resistant to
      protease and heat treatments, and it protects the telomeric probe from
      degradation by various DNA-modifying enzymes. Resistance of the complex to
      bacterial alkaline phosphatase suggests that mtTBP binds the very end of the
      molecule. We purified mtTBP to near homogeneity using DNA affinity chromatography
      based on the telomeric oligonucleotide covalently bound to Sepharose. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoretic analysis of the purified
      fractions revealed the presence of a protein with an apparent molecular mass of
      approximately 15 kDa. UV cross-linking and gel filtration chromatography
      experiments suggested that native mtTBP is probably a homo-oligomer. MtTBP of C.
      parapsilosis is the first identified protein that specifically binds to telomeres
      of linear mitochondrial DNA.

PMID- 9006956
TI  - Multiple molecular chaperones complex with misfolded large oligomeric
      glycoproteins in the endoplasmic reticulum.
AB  - Thyroglobulin (Tg), the major protein secreted by thyroid epithelial cells and
      precursor of thyroid hormones, is a large dimeric glycoprotein with multiple
      disulfide bonds. The folding and assembly of this complex molecule begins in the
      endoplasmic reticulum (ER) and is likely to involve a variety of reactions
      catalyzed by molecular chaperones (Kuznetsov, G., Chen, L. B., and Nigam, S. K.
      (1994) J. Biol. Chem. 269, 22990-22995). By coimmunoprecipitation in rat thyroid
      cells, we were able to demonstrate that BiP, grp94, ERp72, and grp170, four
      proteins believed to function as specific molecular chaperones, complex with Tg
      during its maturation. The same complex of the four putative chaperones with Tg
      was observed in cells treated with tunicamycin, indicating that these four ER
      chaperones stably associate with Tg when it is misfolded/misassembled due to
      inhibition of its glycosylation. BiP, grp94, and ERp72 were also found to
      associate with Tg in cells in which misfolding was induced by perturbing ER
      calcium stores. To determine if the assembly of a complex between the four
      chaperones and Tg under conditions of misglycosylation was unique to the
      maturation of this particular secretory protein or a more general phenomenon,
      adenovirus-transformed rat thyroid cells that do not synthesize Tg were analyzed.
      In these transformed cells, the only protein these same four chaperones were
      found to complex with was a protein of approximately 200 kDa. This protein was
      subsequently identified as thrombospondin, which, like Tg, is a large oligomeric
      secreted glycoprotein with multiple disulfide bonds. We therefore propose that
      these ER chaperones complex together with a variety of large oligomeric secretory
      glycoproteins as they fold and assemble in the ER.

PMID- 9006957
TI  - ATP-dependent choline phosphate-induced mitogenesis in fibroblasts involves
      activation of pp70 S6 kinase and phosphatidylinositol 3'-kinase through an
      extracellular site. Synergistic mitogenic effects of choline phosphate and
      sphingosine 1-phosphate.
AB  - In serum-starved NIH 3T3 clone 7 fibroblasts, choline phosphate (ChoP) (0.5-1 mM)
      and insulin synergistically stimulate DNA synthesis. Here we report that ATP also
      greatly enhanced the mitogenic effects of ChoP (0.1-1 mM) both in the absence and
      presence of insulin; maximal potentiating effects required 50-100 microM ATP. The
      co-mitogenic effects of ATP were mimicked by adenosine 5'-O-(3-thiotriphosphate),
      adenosine 5'-O-(2-thiodiphosphate), ADP, and UTP, but not by AMP or adenosine,
      indicating the mediatory role of a purinergic P2 receptor. Externally added ChoP
      acted on DNA synthesis without its detectable uptake into fibroblasts, indicating
      that ChoP can be a mitogen only if it is released from cells. Extracellular ATP
      (10-100 microM) induced extensive release of ChoP from fibroblasts. ChoP had
      negligible effects, even in the presence of ATP or insulin, on the activity state
      of p42/p44 mitogen-activated protein kinases, while in combination these agents
      stimulated the activity of phosphatidylinositol 3'-kinase (PI 3'-kinase).
      Expression of a dominant negative mutant of the p85 subunit of PI 3'-kinase or
      treatments with the PI 3'-kinase inhibitor wortmannin only partially
      (approximately 40-50%) reduced the combined effects of ChoP, ATP, and insulin on
      DNA synthesis; in contrast, the pp70 S6 kinase inhibitor rapamycin almost
      completely inhibited these effects. ATP and insulin also potentiated, while
      rapamycin strongly inhibited, the mitogenic effects of sphingosine 1-phosphate
      (S1P). Furthermore, even maximally effective concentrations of ChoP and S1P
      synergistically stimulated DNA synthesis. The results indicate that in the
      presence of extracellular ATP and/or S1P, ChoP induces mitogenesis through an
      extracellular site by mechanisms involving the activation of pp70 S6 kinase and,
      to a lesser extent, PI 3'-kinase.

PMID- 9006958
TI  - Pancreatic stone protein (lithostathine), a physiologically relevant pancreatic
      calcium carbonate crystal inhibitor?
AB  - Apart from digestive enzymes, pancreatic juice contains several proteins that are
      not directly involved in digestion. One of these, lithostathine, has been
      reported to exhibit calcite crystal inhibitor activity in vitro. As pancreatic
      juice is supersaturated with respect to calcium carbonate, it was hypothesized
      that lithostathine stabilizes pancreatic juice. Lithostathine is cleaved by trace
      amounts of trypsin, resulting in a C-terminal polypeptide and an N-terminal
      undecapeptide, which has been identified as the active site of lithostathine
      regarding crystal inhibition. We produced rat lithostathine in a baculovirus
      expression system. In order to test its functional activity, the protein was
      purified using a nondenaturing multi-step procedure. In the low micromolar range,
      recombinant rat lithostathine in vitro exhibited calcite crystal inhibitor
      activity, confirming earlier reports. Limited tryptic proteolysis of recombinant
      lithostathine was performed, and the two cleavage products were separated; the C
      terminal polypeptide was precipitated by centrifugation, and the N-terminal
      undecapeptide was purified by high performance liquid chromatography. Only the C
      terminal peptide displayed measurable calcite crystal inhibitory activity.
      Furthermore, synthetic undecapeptides with identical sequence to the N-terminal
      undecapeptides of rat or human lithostathine were inactive. However, when tested
      in the same in vitro assays, other pancreatic or extra-pancreatic proteins show
      inhibitory activity in the same concentration range as lithostathine, and
      inorganic phosphate is active as well. Based on these findings it seems unlikely
      that lithostathine is a physiologically relevant calcite crystal inhibitor. The
      name "lithostathine" is therefore inappropriate, and the protein's key function
      remains to be elucidated.

PMID- 9006959
TI  - Functional analysis of surfactant protein B (SP-B) promoter. Sp1, Sp3, TTF-1, and
      HNF-3alpha transcription factors are necessary for lung cell-specific activation
      of SP-B gene transcription.
AB  - Surfactant protein B (SP-B) is essential for maintenance of biophysical
      properties and physiological function of pulmonary surfactant. SP-B mRNA
      expression is restricted to alveolar type II epithelial cells and bronchiolar
      epithelial cells (Clara cells) of adult lung. We previously (Margana, R. K., and
      Boggaram, V. (1996) Am. J. Physiol. 270, L601-L612) found that a minimal promoter
      region (-236 to +39) of rabbit SP-B gene is sufficient for high level expression
      of chloramphenicol acetyltransferase reporter gene in NCI-H441 cells, a cell line
      with characteristics of Clara cells. In the present study we used mutational
      analysis, electrophoretic mobility shift assays, and DNase I footprinting to
      identify cis-DNA regulatory elements and trans-acting protein factors required
      for lung cell-specific expression of SP-B gene. We found that in addition to
      thyroid transcription factor 1 (TTF-1) and hepatocyte nuclear factor 3alpha (HNF
      3alpha) binding sites, two spatially separate DNA sequences that bind Sp1 and Sp3
      factors are necessary for the maintenance of SP-B promoter activity. Mutation of
      any one of the transcription factor binding sites caused a significant reduction
      in SP-B promoter activity suggesting that Sp1, Sp3, and TTF-1 and HNF-3alpha
      interact cooperatively with SP-B promoter to activate gene transcription.

PMID- 9006960
TI  - Induction by glucose of genes coding for glycolytic enzymes in a pancreatic beta
      cell line (INS-1).
AB  - Chronic elevation in glucose has pleiotropic effects on the pancreatic beta-cell
      including a high rate of insulin secretion at low glucose, beta-cell hypertrophy,
      and hyperplasia. These actions of glucose are expected to be associated with the
      modulation of the expression of a number of glucose-regulated genes that need to
      be identified. To further investigate the molecular mechanisms implicated in
      these adaptation processes to hyperglycemia, we have studied the regulation of
      genes encoding key glycolytic enzymes in the glucose-responsive beta-cell line
      INS-1. Glucose (from 5 to 25 mM) induced phosphofructokinase-1 (PFK-1) isoform C,
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (4-fold), and L-pyruvate kinase
      (L-PK) (7-fold) mRNAs. In contrast the expression level of the glucokinase (Gk)
      and 6-phosphofructo-2-kinase transcripts remained unchanged. Following a 3-day
      exposure to elevated glucose, a similar induction was observed at the protein
      level for PFK-1 (isoforms C, M, and L), GAPDH, and L-PK, whereas M-PK expression
      only increased slightly. The study of the mechanism of GAPDH induction indicated
      that glucose increased the transcriptional rate of the GAPDH gene but that both
      transcriptional and post transcriptional effects contributed to GAPDH mRNA
      accumulation. 2-Deoxyglucose did not mimic the inductive effect of glucose,
      suggesting that increased glucose metabolism is involved in GAPDH gene induction.
      These changes in glycolytic enzyme expression were associated with a 2-3-fold
      increase in insulin secretion at low (2-5 mM) glucose. The metabolic activity of
      the cells was also elevated, as indicated by the reduction of the artificial
      electron acceptor 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium. A marked
      deposition of glycogen, which was readily mobilized upon lowering of the ambient
      glucose, and increased DNA replication were also observed in cells exposed to
      elevated glucose. The results suggest that a coordinated induction of key
      glycolytic enzymes as well as massive glycogen deposition are implicated in the
      adaptation process of the beta-cell to hyperglycemia to allow for chronically
      elevated glucose metabolism, which, in this particular fuel-sensitive cell, is
      linked to metabolic coupling factor production and cell activation.

PMID- 9006961
TI  - Transcriptional induction of cholesterol 7alpha-hydroxylase by dexamethasone in
      L35 hepatoma cells requires sulfhydryl reducing agents.
AB  - It is known that hepatic levels of reduced glutathione correlate with the
      activity of the liver-specific enzyme cholesterol-7alpha-hydroxylase. We examined
      the possibility that sulfhydryl reducing agents activate transcription of
      cholesterol 7alpha-hydroxylase. Adding dithiothreitol (DTT, 1 mM) and
      dexamethasone to L35 hepatoma cells increased the content of 7alpha-hydroxylase
      mRNA 3-fold above the levels observed with dexamethasone alone. Without
      dexamethasone, DTT had no affect. The addition of reduced glutathione to L35
      cells demonstrated a similar potentiation of expression dependent on
      dexamethasone. Nuclear run-on assays showed that in the presence of both
      dexamethasone and DTT, the transcription of the 7alpha-hydroxylase gene was
      clearly increased. In contrast, by itself, dexamethasone did not cause a
      detectable increase in the transcription of the 7alpha-hydroxylase gene.
      Dexamethasone and DTT did not affect the transcription of beta-actin, suggesting
      a selective induction of the 7alpha-hydroxylase gene. DTT reversed repression of
      7alpha-hydroxylase expression by insulin but not the repression by phorbol ester.
      Our data show for the first time that the sulfhydryl redox potential of the
      hepatocyte (i.e. level of reduced glutathione) has a marked influence on the
      transcription and expression of the liver-specific gene 7alpha-hydroxylase.

PMID- 9006962
TI  - Extracellular ATP induces anchorage-independent expression of cyclin A and
      rescues the transformed phenotype of a ras-resistant mutant cell line.
AB  - Anchorage-independent growth is characteristic of neoplastic cells, but the
      signal transduction pathways that mediate this phenotype are poorly understood.
      Several important cell cycle events are dependent on cell-substratum adhesion in
      non-transformed cells, including activation of G1 cyclin-dependent kinases and
      expression of cyclin A; the adhesion requirement of these events is abrogated in
      Ras-transformed cells. The ER-1-2 mutant rat fibroblast cell line is: 1)
      resistant to Ras-mediated, anchorage-independent growth; 2) defective in Ras
      mediated, adhesion-independent expression of cyclin A, but not adhesion
      independent activation of cyclin-dependent kinases; and 3) rescued for Ras
      induced, anchorage-independent growth by ectopic expression of cyclin A. We
      report here that extracellular ATP induces adhesion-independent expression of
      cyclin A and rescues growth in soft agar by ER-1-2 cells that express Ras. ADP,
      AMP and the non-hydrolyzable analog adenosine 5'-(beta, gamma-iminodiphosphate)
      are also effective, but adenosine is not. Adenine nucleotide-induced growth in
      soft agar is inhibited by reactive blue 2, an antagonist of some P2
      purinoceptors. ATP does not induce adhesion-independent expression of cyclin A in
      ER-1-2 or control rat fibroblasts that do not express Ras, indicating a
      requirement for additional Ras-regulated signals for expression of this gene; one
      such signal may lead to phosphorylation of the retinoblastoma protein, pRB, and
      related proteins. These results suggest that extracellular ATP could play a role
      in the multistage carcinogenic process in vivo.

PMID- 9006964
TI  - Assembly of immunoglobulin light chains as a prerequisite for secretion. A model
      for oligomerization-dependent subunit folding.
AB  - Oligomeric proteins usually have to assemble into their final quartenary
      structure to be secreted. However, most immunoglobulin (Ig) light (L) chains can
      be exported as free chains, whereas only a few Ig L chains, here referred to as
      export-incompetent, have to assemble with Ig heavy (H) chains into antibody
      molecules to be secreted. In the absence of Ig H chain expression, these export
      incompetent Ig L chains remain bound to BiP as partially folded monomers with
      only one of the two internal disulfide bonds being formed. To understand the
      apparent discrepancy in Ig L chain export, we performed assembly studies with
      chimeric Ig chains and found that the variable (V) domain of the export
      incompetent NS1 kappa chain cannot mediate homodimer formation. Conversely, the V
      domain of the export-competent J558L lambda1 chain supports homodimer formation
      and, concordantly, these Ig L chains are secreted as noncovalently or covalently
      linked homodimers. We show that the export-incompetent mutant lambda1 FS62 chain
      forms disulfide bonds in both domains only upon pairing with Ig H chain and is
      secreted as part of an antibody. Therefore, Ig L chain assembly seems to be a
      prerequisite for complete folding, indicating that Ig L chain secretion generally
      depends on either homo- or heterodimer formation. We discuss a mechanism that
      controls oligomerization by monitoring the conformation of individual subunits
      that cannot proceed in folding prior to successful assembly.

PMID- 9006963
TI  - Induction of the intronic enhancer of the human ciliary neurotrophic factor
      receptor (CNTFRalpha) gene by the TR4 orphan receptor. A member of steroid
      receptor superfamily.
AB  - A conserved hormone response element, CNTFR-DR1 (5'-AGGTCAGAGGTCAGG-3'), has been
      identified in the 5th intron of the alpha component of the ciliary neurotrophic
      factor receptor (CNTFRalpha) gene for the human TR4 orphan receptor (TR4).
      Electrophoretic mobility shift assay showed a specific binding with high affinity
      (Kd = 0.066 nM) between TR4 and the CNTFR-DR1. A reporter gene assay using
      chloramphenicol acetyltransferase demonstrated that the 5th intron of CNTFRalpha
      has an enhancer activity which could be induced by TR4 in a dose-dependent
      manner. Furthermore, our in situ hybridization data showed that abundant TR4
      transcripts were detected in adult brain, in regions of cortical and hippocampal
      neurons, as well as in many developing neural structures, including brain, spinal
      cord, ganglia (sympathetic and sensory), and neuronal epithelia (retinal, otic,
      olfactory, and gustatory). The striking similarities in the expression patterns
      of TR4 and CNTFRalpha in the developing and postnatal nervous systems further
      support the potential role of TR4 in neurogenesis. Collectively, these data
      suggest that the human CNTFRalpha gene could represent the first identified
      neural-specific gene induced by TR4.

PMID- 9006965
TI  - Cloning, characterization, and expression of a G-protein-coupled receptor from
      Lymnaea stagnalis and identification of a leucokinin-like peptide, PSFHSWSamide,
      as its endogenous ligand.
AB  - Neuropeptides are known to be important signaling molecules in several neural
      systems of the pond snail Lymnaea stagnalis. Although the functions of these
      peptides have been studied in many neurons, the nature of the postsynaptic signal
      transduction is mainly unknown. The cloning and characterization of neuropeptide
      receptors in Lymnaea thus would be very valuable in further elucidating
      peptidergic pathways. Indirect evidence suggests that these neuropeptides operate
      via G-protein-coupled mechanisms indicating the presence of G-protein-coupled
      receptors as the initial postsynaptic targets. Here we describe the cloning of a
      neuropeptide receptor from Lymnaea and the isolation of an endogenous ligand.
      This peptide, PSFHSWSamide, belongs to the leucokinin family of peptides, and,
      thus, this Lymnaea receptor is the first example of a leucokinin-like
      neuropeptide receptor, representing a new subfamily of G-protein-coupled
      neuropeptide receptors.

PMID- 9006966
TI  - Developmental regulation of synaptotagmin I, II, III, and IV mRNAs in the rat
      CNS.
AB  - Synaptotagmin I is an abundant synaptic vesicle protein that has an essential
      function in mediating Ca2+-triggered neurotransmitter release. We have analyzed
      the distribution of four neural synaptotagmin isoforms during postnatal
      development of the rat CNS by in situ hybridization. Synaptotagmin I, II, III,
      and IV genes have distinct patterns of spatiotemporal expression except in
      cerebellum granule cells, where the four transcripts were detected during the
      formation of parallel fiber/Purkinje cell synapses. Throughout development
      synaptotagmin I mRNAs were widely expressed in brain, whereas synaptotagmin II
      transcripts were predominant in spinal cord. At all stages synaptotagmin III
      mRNAs were expressed uniformly in most neurons examined, although at a low level.
      Synaptotagmin I, II, and III gene expressions mainly increased during development
      and persisted in adulthood, mirroring neuronal differentiation. Conversely,
      synaptotagmin IV transcripts were predominant during perinatal development in a
      heterogeneous population of neurons and subsequently were expressed uniformly at
      a low level. Intense labeling was observed in the hippocampal CA3 field and in
      the subiculum, but not in the CA1 field, of the newborn rat. In cerebral cortex,
      lamina-specific labeling was detected with a high expression in cell layer V.
      Only a small number of Purkinje cell clusters were labeled in the flocculus and
      paraflocculus of the cerebellum. Heterogeneous sets of neurons expressing
      synaptotagmin IV gene also were observed in spinal cord. We thus speculate that
      synaptotagmin IV may a play a role in the development of the mammalian nervous
      system.

PMID- 9006967
TI  - Characterization of a CNS cell line, CAD, in which morphological differentiation
      is initiated by serum deprivation.
AB  - A CNS catecholaminergic cell line, Cath.a, was established by targeted
      oncogenesis in transgenic mice. Cath.a cells express neuronal properties but lack
      neuronal morphology. Here, we describe a variant of Cath.a, called CAD (Cath.a
      differentiated), in which reversible morphological differentiation can be
      initiated by removal of serum or exogenously added protein from the medium. In
      serum- or protein-free media, CAD cells stop proliferating and extend long
      processes. Differentiated CAD cells can be maintained without serum or protein
      for at least 6 weeks. CAD cells are distinct from Cath.a cells; most significant,
      the original immortalizing oncogene, SV40 T antigen, was spontaneously lost. By
      immunostaining or immunoblotting, we show that CAD cells express neuron-specific
      proteins, such as class III beta-tubulin, GAP-43, SNAP-25, and synaptotagmin, but
      not GFAP. Ultrastructurally, processes from differentiated CAD cells have
      abundant parallel microtubules and intermediate filaments, and bear varicosities
      that contain both large dense-core vesicles/granules (120-160 nm) and smaller
      clear vesicles (60-80 nm). Additionally, CAD cells express enzymatically active
      tyrosine hydroxylase and accumulate L-DOPA. CAD cells exhibit biochemical and
      morphological characteristics of primary neurons and provide an unique tool for
      studying neuronal differentiation.

PMID- 9006968
TI  - Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl
      phosphatidylethanolamine, in rat brain.
AB  - It has been suggested that anandamide (N-arachidonoylethanolamine), an endogenous
      cannabinoid substance, may be produced through Ca2+-stimulated hydrolysis of the
      phosphatidylethanolamine (PE) derivative N-arachidonoyl PE. The presence of N
      arachidonoyl PE in adult brain tissue and the enzyme pathways that underlie its
      biosynthesis are, however, still undetermined. We report here that rat brain
      tissue contains both anandamide (11 +/- 7 pmol/gm wet tissue) and N-arachidonoyl
      PE (22 +/- 16 pmol/gm), as assessed by gas chromatography/mass spectrometry. We
      describe a N-acyltransferase activity in brain that catalyzes the biosynthesis of
      N-arachidonoyl PE by transferring an arachidonate group from the sn-1 carbon of
      phospholipids to the amino group of PE. We also show that sn-1 arachidonoyl
      phospholipids are present in brain, where they constitute approximately 0.5% of
      total phospholipids. N-acyltransferase activity is Ca2+ dependent and is enriched
      in brain and testis. Within the brain, N-acyltransferase activity is highest in
      brainstem; intermediate in cortex, striatum, hippocampus, medulla, and
      cerebellum; and lowest in thalamus, hypothalamus, and olfactory bulb.
      Pharmacological inhibition of N-acyltransferase activity in primary cultures of
      cortical neurons prevents Ca2+-stimulated N-arachidonoyl PE biosynthesis. Our
      results demonstrate, therefore, that rat brain tissue contains the complement of
      enzymatic activity and lipid substrates necessary for the biosynthesis of the
      anandamide precursor N-arachidonoyl PE. They also suggest that biosynthesis of N
      arachidonoyl PE and formation of anandamide are tightly coupled processes, which
      may concomitantly be stimulated by elevations in intracellular Ca2+ occurring
      during neural activity.

PMID- 9006970
TI  - G1/S cell cycle blockers and inhibitors of cyclin-dependent kinases suppress
      camptothecin-induced neuronal apoptosis.
AB  - Previous studies have demonstrated that G1/S cell cycle blockers and inhibitors
      of cyclin-dependent kinases (CDKs) prevent the death of nerve growth factor (NGF)
      deprived PC12 cells and sympathetic neurons, suggesting that proteins normally
      involved in the cell cycle may also serve to regulate neuronal apoptosis. Past
      findings additionally demonstrate that DNA-damaging agents, such as the DNA
      topoisomerase (topo-I) inhibitor camptothecin, also induce neuronal apoptosis. In
      the present study, we show that camptothecin-induced apoptosis of PC12 cells,
      sympathetic neurons, and cerebral cortical neurons is suppressed by the G1/S
      blockers deferoxamine and mimosine, as well as by the CDK-inhibitors flavopiridol
      and olomoucine. In each case, the IC50 values were similar to those reported for
      inhibition of death induced by NGF-deprivation. In contrast, other agents that
      arrest DNA synthesis, such as aphidicolin and N-acetylcysteine, failed to block
      death. This suggests that the inhibition of DNA synthesis per se is insufficient
      to provide protection from camptothecin. We find additionally that the cysteine
      aspartase family protease inhibitor zVAD-fmk inhibits apoptosis evoked by NGF
      deprivation but not camptothecin treatment. Thus, despite their shared
      sensitivity to G1/S blockers and CDK inhibitors, the apoptotic pathways triggered
      by these two causes of death diverge at the level of the cysteine aspartase. In
      summary, neuronal apoptosis induced by the DNA-damaging agent camptothecin
      appears to involve signaling pathways that normally control the cell cycle. The
      consequent death signals of such deregulation, however, are different from those
      that result from trophic factor deprivation.

PMID- 9006969
TI  - Modulation of the cloned skeletal muscle L-type Ca2+ channel by anchored cAMP
      dependent protein kinase.
AB  - Ca2+ influx through skeletal muscle Ca2+ channels and the force of contraction
      are increased in response to beta-adrenergic stimulation and high-frequency
      electrical stimulation. These effects are thought to be mediated by cAMP
      dependent phosphorylation of the skeletal muscle Ca2+ channel. Modulation of the
      cloned skeletal muscle Ca2+ channel by cAMP-dependent phosphorylation and by
      depolarizing prepulses was reconstituted by transient expression in tsA-201 cells
      and compared to modulation of the native skeletal muscle Ca2+ channel as
      expressed in mouse 129CB3 skeletal muscle cells. The heterologously expressed
      Ca2+ channel consisting of alpha1, alpha2delta, and beta subunits gave currents
      that were similar in time course, current density, and dihydropyridine
      sensitivity to the native Ca2+ channel. cAMP-dependent protein kinase (PKA)
      stimulation by Sp-5,6-DCl-cBIMPS (cBIMPS) increased currents through both native
      and expressed channels two- to fourfold. Tail currents after depolarizations to
      potentials between -20 and +80 mV increased in amplitude and decayed more slowly
      as either the duration or potential of the depolarization was increased. The time
      and voltage-dependent slowing of channel deactivation required the activity of
      PKA, because it was enhanced by cBIMPS and reduced or eliminated by the peptide
      PKA inhibitor PKI (5-24) amide. This voltage-dependent modulation of the cloned
      skeletal muscle Ca2+ channel by PKA also required anchoring of PKA by A-Kinase
      Anchoring Proteins because it was blocked by peptide Ht 31, which disrupts such
      anchoring. The results show that the skeletal muscle Ca2+ channel expressed in
      heterologous cells is modulated by PKA at rest and during depolarization and that
      this modulation requires anchored protein kinase, as it does in native skeletal
      muscle cells.

PMID- 9006971
TI  - Disruption of the metallothionein-III gene in mice: analysis of brain zinc,
      behavior, and neuron vulnerability to metals, aging, and seizures.
AB  - Metallothionein-III (MT-III), a brain-specific member of the metallothionein
      family of metal-binding proteins, is abundant in glutamatergic neurons that
      release zinc from their synaptic terminals, such as hippocampal pyramidal neurons
      and dentate granule cells. MT-III may be an important regulator of zinc in the
      nervous system, and its absence has been implicated in the development of
      Alzheimer's disease. However, the roles of MT-III in brain physiology and
      pathophysiology have not been elucidated. Mice lacking MT-III because of targeted
      gene inactivation were generated to evaluate the neurobiological significance of
      MT-III. MT-III-deficient mice had decreased concentrations of zinc in several
      brain regions, including hippocampus, but the pool of histochemically reactive
      zinc was not disturbed. Mutant mice exhibited normal spatial learning in the
      Morris water maze and were not sensitive to systemic zinc or cadmium exposure. No
      neuropathology or behavioral deficits were detected in 2-year-old MT-III
      deficient mice, but the age-related increase in glial fibrillary acidic protein
      expression was more pronounced in mutant brain. MT-III-deficient mice were more
      susceptible to seizures induced by kainic acid and subsequently exhibited greater
      neuron injury in the CA3 field of hippocampus. Conversely, transgenic mice
      containing elevated levels of MT-III were more resistant to CA3 neuron injury
      induced by seizures. These observations suggest a potential role for MT-III in
      zinc regulation during neural stimulation.

PMID- 9006972
TI  - Retrograde transport and steady-state distribution of 125I-nerve growth factor in
      rat sympathetic neurons in compartmented cultures.
AB  - We have used compartmented cultures of rat sympathetic neurons to quantitatively
      examine the retrograde transport of 125I-nerve growth factor (NGF) supplied to
      distal axons and to characterize the cellular events that maintain steady-state
      levels of NGF in cell bodies. In cultures allowed to reach steady-state 125I-NGF
      transport, cell bodies contained only 5-30% of the total neuron-associated 125I
      NGF, whereas 70-95% remained associated with the distal axons. This was true over
      an 8 pM to 1.5 nM 125I-NGF concentration range, indicating that saturation of
      high affinity receptors could not account for the large fraction of 125I-NGF
      remaining in axons. Dissociation assays indicated that 85% of 125I-NGF associated
      with distal axons was surface-bound. At steady-state, only 2-25% of the distal
      axon-associated 125I-NGF was retrogradely transported each hour, with higher
      transport rates associated with younger cultures and lower 125I-NGF
      concentrations. The velocity of 125I-NGF retrograde transport was estimated at 10
      20 mm/hr. However, as in a previous report, almost no 125I-NGF transport was
      observed during the first hour after 125I-NGF administration, indicating a
      significant lag between receptor binding and loading onto the retrograde
      transport system. During 125I-NGF transport through axons spanning an
      intermediate compartment in five-compartment cultures, little or no 125I-NGF was
      degraded or released from the axons. After transport, 125I-NGF was degraded with
      a half-life of 3 hr. In summary, although some cellular events promoted NGF
      accumulation in cell bodies, distal axons represented by far the principal site
      of NGF-receptor interaction at steady-state as a result of a low retrograde
      transport rate.

PMID- 9006973
TI  - Neurotransmitter- and growth factor-induced cAMP response element binding protein
      phosphorylation in glial cell progenitors: role of calcium ions, protein kinase
      C, and mitogen-activated protein kinase/ribosomal S6 kinase pathway.
AB  - To understand how extracellular signals may produce long-term effects in neural
      cells, we have analyzed the mechanism by which neurotransmitters and growth
      factors induce phosphorylation of the transcription factor cAMP response element
      binding protein (CREB) in cortical oligodendrocyte progenitor (OP) cells.
      Activation of glutamate receptor channels by kainate, as well as stimulation of G
      protein-coupled cholinergic receptors by carbachol and tyrosine kinase receptors
      by basic fibroblast growth factor (bFGF), rapidly leads to mitogen-activated
      protein kinase (MAPK) phosphorylation and ribosomal S6 kinase (RSK) activation.
      Kainate and carbachol activation of the MAPK pathway requires extracellular
      calcium influx and is accompanied by protein kinase C (PKC) induction, with no
      significant increase in GTP binding to Ras. Conversely, growth factor-stimulated
      MAPK phosphorylation is independent of extracellular calcium and is accompanied
      by Ras activation. Both basal and stimulated MAPK activity in OP cells are
      influenced by cytoplasmic calcium levels, as shown by their sensitivity to the
      calcium chelator bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid. The
      kinetics of CREB phosphorylation in response to the various agonists corresponds
      to that of MAPK activation. Moreover, CREB phosphorylation and MAPK activation
      are similarly affected by calcium ions. The MEK inhibitor PD 098059, which
      selectively prevents activation of the MAPK pathway, strongly reduces induction
      of CREB phosphorylation by kainate, carbachol, bFGF, and the phorbol ester TPA.
      We propose that in OPs the MAPK/RSK pathway mediates CREB phosphorylation in
      response to calcium influx, PKC activation, and growth factor stimulation.

PMID- 9006974
TI  - Chronic alcohol consumption and withdrawal do not induce cell death in the
      suprachiasmatic nucleus, but lead to irreversible depression of peptide
      immunoreactivity and mRNA levels.
AB  - There is evidence that chronic ethanol treatment (CET) disrupts the biological
      rhythms of various brain functions and behaviors. Because the suprachiasmatic
      nucleus (SCN) is widely recognized as the dominant pacemaker of the circadian
      system, we have examined the effects of CET and withdrawal on the main
      morphological features and chemoarchitecture of this hypothalamic nucleus. Groups
      of rats ethanol-treated for 6 and 12 months were compared with withdrawn rats
      (ethanol-treated for 6 months and then switched to a normal diet for an
      additional 6 months) and with groups of age-matched control and pair-fed control
      rats. The volume and the total number of neurons of the SCN were estimated from
      conventionally stained material, whereas the total number of astrocytes and of
      neurons containing vasopressin (AVP), vasoactive intestinal polypeptide (VIP),
      gastrin-releasing peptide (GRP), and somatostatin (SS) were estimated from
      immunostained sections. The estimates were obtained using unbiased stereological
      methods, based on Cavalieri's principle and the optical fractionator. The volume
      of the SCN and the total number of SCN neurons and astrocytes did not vary among
      groups. We found, however, that CET induced a significant reduction in the total
      number of AVP-, VIP-, GRP-, and SS-containing neurons. Withdrawal from alcohol
      did not reduce but rather augmented the loss of VIP- and GRP-immunoreactive
      neurons. The CET-induced neurochemical alterations seem to result from a decrease
      in neuropeptide synthesis, as revealed by the reduction in AVP and VIP mRNA
      levels demonstrated by in situ hybridization with radioactively labeled 48-mer
      AVP and 30-mer VIP probes. It is thus possible to conclude that the irreversible
      CET-induced changes in the neurochemistry of the SCN might underpin the
      disturbances in circadian rhythms observed after long-term alcohol consumption.

PMID- 9006975
TI  - Arg-Gly-Asp-Ser-selective adhesion and the stabilization of long-term
      potentiation: pharmacological studies and the characterization of a candidate
      matrix receptor.
AB  - Peptides known to block the extracellular interactions of adhesion receptors
      belonging to a subclass of the integrin family were tested for their effects on
      the stabilization of long-term potentiation (LTP) in hippocampal slices. Theta
      burst stimulation delivered after infusions of Gly-Ala-Val-Ser-Thr-Ala (GAVSTA)
      resulted in a potentiation effect that decayed steadily over a period of 40 min;
      LTP elicited in the presence of inactive control peptides remained stable over
      this time period. GAVSTA had no detectible influence on baseline responses,
      induction processes, or the initial degree of potentiation. Infusions of integrin
      antagonists after application of theta bursts also resulted in the occurrence of
      a decremental form of LTP. Affinity chromatography was then used in an effort to
      identify targets of the structurally dissimilar integrin blockers that disrupt
      LTP stabilization. Both integrin antagonists Gly-Arg-Gly-Asp-Ser-Pro and GAVSTA
      eluted a major species of 55 kDa (synaptegrin-1) from GRGDSP-affinity columns
      that had been loaded with solubilized synaptic membranes; lesser concentrations
      of three polypeptides of approximately 20, 27, and 30 kDa were also collected.
      Synaptegrin-1 was labeled by antibodies to the RGDS-binding integrin alpha5beta1.
      In addition, the synaptegrin, as well as the 27 kDa, protein was found to
      copurify with pre- and postsynaptic markers during the isolation of forebrain
      synaptosomes. These results indicate that a matrix recognition event occurring
      several minutes after induction of LTP is a necessary step in the stabilization
      of potentiated synapses; they also identify an integrin-like matrix receptor of
      55 kDa that may contribute to this event.

PMID- 9006976
TI  - The intracellular loop between domains I and II of the B-type calcium channel
      confers aspects of G-protein sensitivity to the E-type calcium channel.
AB  - Neuronal voltage-dependent calcium channels undergo inhibitory modulation by G
      protein activation, generally involving both kinetic slowing and steady-state
      inhibition. We have shown previously that the beta-subunit of neuronal calcium
      channels plays an important role in this process, because when it is absent,
      greater receptor-mediated inhibition is observed (). We therefore hypothesized
      that the calcium channel beta-subunits normally may occlude G-protein-mediated
      inhibition. Calcium channel beta-subunits bind to the cytoplasmic loop between
      transmembrane domains I and II of the alpha1-subunits (). We have examined the
      hypothesis that this loop is involved in G-protein-mediated inhibition by making
      chimeras containing the I-II loop of alpha1B or alpha1A inserted into alpha1E
      (alpha1EBE and alpha1EAE, respectively). This strategy was adopted because
      alpha1B (the molecular counterpart of N-type channels) and, to a lesser extent,
      alpha1A (P/Q-type) are G-protein-modulated, whereas this has not been observed to
      any great extent for alpha1E. Although alpha1B, coexpressed with alpha2-delta and
      beta1b transiently expressed in COS-7 cells, showed both kinetic slowing and
      steady-state inhibition when recorded with GTPgammaS in the patch pipette, both
      of which were reversed with a depolarizing prepulse, the chimera alpha1EBE (and,
      to a smaller extent, alpha1EAE) showed only kinetic slowing in the presence of
      GTPgammaS, and this also was reversed by a depolarizing prepulse. These results
      indicate that the I-II loop may be the molecular substrate of kinetic slowing but
      that the steady-state inhibition shown by alpha1B may involve a separate site on
      this calcium channel.

PMID- 9006977
TI  - Regional expression and cellular localization of the alpha1 and beta subunit of
      high voltage-activated calcium channels in rat brain.
AB  - The neuronal high voltage-activated calcium channels are a family of ion channels
      composed from up to five different alpha1 and four different beta subunits. The
      neuronal distribution and subunit composition of calcium channels were
      investigated using subunit-specific antibodies and riboprobes. The beta subunit
      specific antibodies identified the presence of beta1a in skeletal muscle; beta2
      in heart; and beta2, beta3, and beta4 in brain. The beta3 protein was widely
      distributed in rat brain, with prominent labeling of olfactory bulb, cortex,
      hippocampus, and habenula. The beta4 protein was also widely expressed, most
      prominently in the cerebellum. beta2 protein was expressed at only low levels. In
      situ hybridization with beta subunit-specific riboprobes confirmed the
      differential expression pattern of the individual subunits. Hybridization with
      riboprobes specific for the alpha1A, alpha1B, alpha1C, and alpha1D subunits
      showed a broad distribution of alpha1A and alpha1B transcripts, whereas the
      expression level of alpha1C and alpha1D mRNA was lower and more spatially
      restricted. The overall expression pattern and cellular localization suggested
      that beta4 may associate predominantly, but probably not exclusively, with the
      alpha1A subunit, and beta3 with the alpha1B subunit. In certain brain areas such
      as the habenula, the beta3 subunit may associate with other alpha1 subunits too.
      Furthermore, the beta2 subunit may form complexes with different alpha1 subunits
      in brain and cardiac muscle. These results demonstrate that a given beta subunit
      may associate with different alpha1 subunits in a cell type-dependent manner,
      contributing to the diversity of the neuronal calcium channels.

PMID- 9006978
TI  - Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene
      inactivation inhibits delta subunit expression.
AB  - Cerebellar granule cells express six GABAA receptor subunits abundantly (alpha1,
      alpha6, beta2, beta3, gamma2, and delta) and assemble various pentameric receptor
      subtypes with unknown subunit compositions; however, the rules guiding receptor
      subunit assembly are unclear. Here, removal of intact alpha6 protein from
      cerebellar granule cells allowed perturbations in other subunit levels to be
      studied. Exon 8 of the mouse alpha6 subunit gene was disrupted by homologous
      recombination. In alpha6 -/- granule cells, the delta subunit was selectively
      degraded as seen by immunoprecipitation, immunocytochemistry, and immunoblot
      analysis with delta subunit-specific antibodies. The delta subunit mRNA was
      present at wild-type levels in the mutant granule cells, indicating a post
      translational loss of the delta subunit. These results provide genetic evidence
      for a specific association between the alpha6 and delta subunits. Because in
      alpha6 -/- neurons the remaining alpha1, beta2/3, and gamma2 subunits cannot
      rescue the delta subunit, certain potential subunit combinations may not be found
      in wild-type cells.

PMID- 9006979
TI  - Neuropeptide amidation in Drosophila: separate genes encode the two enzymes
      catalyzing amidation.
AB  - In vertebrates, the two-step peptide alpha-amidation reaction is catalyzed
      sequentially by two enzymatic activities contained within one bifunctional enzyme
      called PAM (peptidylglycine alpha-amidating mono-oxygenase). Drosophila head
      extracts contained both of these PAM-related enzyme activities: a mono-oxygenase
      (PHM) and a lyase (PAL). However, no bifunctional PAM protein was detected. We
      identified cDNAs encoding an active mono-oxygenase that is highly homologous to
      mammalian PHM. PHM-like immunoreactivity was found within diverse larval tissues,
      including the CNS, endocrine glands, and gut epithelium. Northern and Western
      blot analyses demonstrate RNA and protein species corresponding to the cloned
      PHM, but not to a bifunctional PAM, leading us to predict the existence of
      separate PHM and PAL genes in Drosophila. The Drosophila PHM gene displays an
      organization of exons that is highly similar to the PHM-encoding portion of the
      rat PAM gene. Genetic analysis was consistent with the prediction of separate PHM
      and PAL gene functions in Drosophila: a P element insertion line containing a
      transposon within the PHM transcription unit displayed strikingly lower PHM
      enzyme levels, whereas PAL levels were increased slightly. The lethal phenotype
      displayed by the dPHM P element insertion indicates a widespread essential
      function. Reversion analysis indicated that the lethality associated with the
      insertion chromosome likely is attributable to the P element insertion. These
      combined data indicate a fundamental evolutionary divergence in the genes coding
      for critical neurotransmitter biosynthetic enzymes: in Drosophila, the two enzyme
      activities of PAM are encoded by separate genes.

PMID- 9006980
TI  - AMPA and NMDA glutamate receptor subunits in midbrain dopaminergic neurons in the
      squirrel monkey: an immunohistochemical and in situ hybridization study.
AB  - The objective of the present study was to analyze the cellular and subcellular
      localization of ionotropic glutamate receptor subunits in midbrain dopaminergic
      neurons in the squirrel monkey. This was achieved by means of
      immunohistochemistry at light and electron microscopic levels and in situ
      hybridization histochemistry. Colocalization studies show that nearly all
      dopaminergic neurons in both the ventral and dorsal tiers of the substantia nigra
      compacta (SNc-v, SNc-d) and the ventral tegmental area (VTA) are immunoreactive
      for AMPA (GluR1, GluR2/3, and GluR4) and NMDAR1 receptor subunits, but not for
      NMDAR2A/B subunits. The immunoreactivity of the receptor subunits is associated
      mainly with perikarya and dendritic shafts. Apart from the intensity of
      immunolabeling for the GluR4 subunit, which is quite similar for the different
      groups of midbrain dopaminergic neurons, the overall intensity of immunostaining
      for the other subunits is higher in the SNc-v and SNc-d than in the VTA. In line
      with these observations, in situ hybridization shows that the average level of
      labeling for the GluR2 and NMDAR1 subunit mRNAs is significantly higher in the
      SNc-v than in the VTA, and for the NMDAR1 subunit, higher in the SNc-v than in
      the SNc-d. In contrast, no significant difference was found for the level of
      GluR1 mRNA labeling among the three groups of midbrain dopaminergic neurons. At
      the subcellular level in the SNc-v, AMPA (GluR1 and GluR2/3) and NMDAR1 receptor
      subunit immunoreactivity is preferentially associated with the postsynaptic
      densities of asymmetric synapses, but occasionally some immunoreactivity is found
      along nonsynaptic portions of plasma membranes of dendrites. A small number of
      preterminal axons, axon terminals, and glial cell processes are also
      immunoreactive. Our observations indicate that the different groups of midbrain
      dopaminergic neurons in primates exhibit a certain degree of heterogeneity with
      regard to the level of expression of some ionotropic glutamate receptor subunits.
      The widespread neuronal and glial localization of glutamate receptor subunits
      suggests that excitatory amino acids may act at different levels to control the
      basal activity and, possibly, to participate in the degeneration of midbrain
      dopaminergic neurons in Parkinson's disease.

PMID- 9006981
TI  - p53 expression induces apoptosis in hippocampal pyramidal neuron cultures.
AB  - The tumor suppressor gene p53 has been implicated in the induction of apoptosis
      in dividing cells. We now show that overexpression of p53 using an adenoviral
      vector in cultured rat hippocampal pyramidal neurons causes widespread neuronal
      death with features typical of apoptosis. p53 overexpression did not induce p21,
      bax, or mdm2 in neurons. X-irradiation of hippocampal neurons induced p53
      immunoreactivity and cell death associated with features typical of apoptosis.
      Overexpression of a constitutively active nonphosphorylatable form of the
      retinoblastoma gene product blocked x-irradiation-induced neuronal death.
      However, overexpression of the cyclin-dependent kinase inhibitor p21 did not.
      Treatment of neurons with transforming growth factor-beta1 protected them from x
      irradiation. These results are consistent with a role for p53 in nerve cell death
      that is distinct from its actions relating to cell cycle arrest.

PMID- 9006982
TI  - A post-transcriptional regulatory mechanism restricts expression of the
      paraneoplastic cerebellar degeneration antigen cdr2 to immune privileged tissues.
AB  - Paraneoplastic cerebellar degeneration (PCD) is believed to be an autoimmune
      disorder initiated by the ectopic expression of a neuron-specific protein in
      breast and ovarian tumors. PCD antisera was used previously to identify several
      cerebellar degeneration-related (cdr) genes encoding putative PCD antigens. We
      have found that the cdr2 gene, which encodes a cytoplasmic leucine zipper protein
      of unknown function, is expressed in PCD-associated tumors, whereas other cdr
      genes are not; thus, cdr2 encodes the PCD tumor antigen. To determine whether the
      expression pattern of cdr2 is consistent with its proposed role in PCD, we have
      isolated the mouse homolog and examined both the mRNA and protein distribution in
      adult tissues. We have found that cdr2 mRNA is expressed in almost all tissues,
      whereas the protein is expressed only in the brain and testis. Within the brain,
      both the cdr2 mRNA and immunoreactivity are confined primarily to neurons in the
      cerebellum and brainstem, the regions most affected in PCD. These results suggest
      first that the tissue-specific expression of cdr2 is regulated at a post
      transcriptional level. Moreover, because the brain and testis are considered to
      be immune-privileged sites, the expression pattern of cdr2 is compatible with the
      autoimmune model of PCD pathogenesis.

PMID- 9006983
TI  - Neurotrophic factors increase neuregulin expression in embryonic ventral spinal
      cord neurons.
AB  - Neuregulins (NRGs) are expressed in spinal cord motor neurons and accumulate at
      the neuromuscular junction where they may increase the synthesis of postsynaptic
      acetylcholine receptors and voltage-gated sodium channels. We demonstrate here
      that NRG expression is selectively increased in rat ventral spinal cord neurons
      at approximately the time that nerve-muscle synapses first form. A rapid increase
      in NRG mRNA and protein expression was induced in vitro in cultured rat spinal
      motor neurons by brain-derived neurotrophic factor, neurotrophin-3, neurotrophin
      4, or glial-cell-line-derived neurotrophic factor. Agrin expression was not
      affected by these factors over the same time course. Brain-derived neurotrophic
      factor, but not neurotrophin-3, selectively regulated immunoglobulin domain
      containing splice variants of NRG, which are likely to be important for binding
      to the synaptic basal lamina. Regulation of NRG expression in motor neurons by
      muscle-derived neurotrophic factors may represent one portion of a reciprocal,
      regulatory loop that promotes neuromuscular synapse development.

PMID- 9006984
TI  - The expression and function of Notch pathway genes in the developing rat eye.
AB  - The Notch gene plays a role in the development of disparate tissues in multiple
      organisms. Because the vertebrate eye is an excellent model system for both
      patterning and cell fate determination, two processes that can involve Notch, we
      examined the expression patterns of Notch 1 and Notch 2, and their ligands Delta
      and Jagged, in the developing rat eye. Notch 1 and Delta were found to be
      expressed in the neural retina during the period of cell fate determination and
      differentiation. Notch 2 was found to be expressed in the non-neuronal
      derivatives of the optic cup, including the pigment epithelium, optic stalk, and
      ciliary body. Jagged was expressed in distinct regions within the optic vesicle,
      ciliary body, and lens, with patterns that changed over time. The potential
      function of Notch 1 in cell-type specification and differentiation was examined
      by introducing a constitutively active form of Notch 1 in vivo using a
      replication-incompetent retrovirus. This form of Notch 1 was found to cause
      abnormal growth and interfere with the differentiation of multiple retinal cell
      types.

PMID- 9006985
TI  - A pacemaker current in dye-coupled hilar interneurons contributes to the
      generation of giant GABAergic potentials in developing hippocampus.
AB  - The establishment of synaptic connections and their refinement during development
      require neural activity. Increasing evidence suggests that spontaneous bursts of
      neural activity within an immature network are mediated by gamma-aminobutyric
      acid via a paradoxical excitatory action. Our data show that in the developing
      hippocampus such synchronous burst activity is generated in the hilar region by
      transiently coupled cells. These cells have been identified as neuronal elements
      because they fire action potentials and they are not positive for the glial
      fibrillary acidic protein staining. Oscillations in hilar cells are "paced" by a
      hyperpolarization-activated current, with properties of Ih. Coactivated
      interneurons synchronously release GABA, which via its excitatory action may
      serve a neurotrophic function during the refinement of hippocampal circuitry.

PMID- 9006986
TI  - Expression and distribution of IGF-1 receptors containing a beta-subunit variant
      (betagc) in developing neurons.
AB  - Betagc is a beta-subunit variant of the insulin-like growth factor-1 (IGF-1)
      receptor highly enriched in growth cone membranes prepared by subcellular
      fractionation of fetal rat brain (). The present study is focused on the
      expression and on the cellular and subcellular distribution of betagc in
      developing neurons and differentiating PC12 cells. In the developing cerebral
      cortex and, at least at early stages, in cultured primary neurons, betagc
      expression was found to be correlated with neurite outgrowth. In PC12 cells
      betagc expression was nerve growth factor (NGF)-dependent and also paralleled
      neurite outgrowth. In contrast, beta-subunits of the insulin receptor and/or of
      other IGF-1 receptors ("betaP5"; detected with antibody AbP5) were downregulated
      as betagc expression increased. Immunofluorescence studies confirmed the
      enrichment of betagc at growth cones and demonstrated morphologically its spatial
      separation from betaP5, which is confined to the perikaryon. At the growth cone,
      betagc colocalizes and associates in a proximal region with microtubules, but it
      seems independent of the more peripheral microfilaments. Some betagc
      immunoreactivity is detected in the perinuclear region of PC12 cells, most likely
      the Golgi complex and its vicinity. betagc seems to emerge from the periphery of
      this structure in an apparently vesicular compartment distinct from that carrying
      synaptophysin to the growth cones. The facts that (1) betagc expression is
      correlated closely with neurite outgrowth, that (2) it is regulated in PC12 cells
      by a neurotrophin, NGF, and that (3) betagc is concentrated in the proximal
      growth cone region raise new questions regarding a possible role of IGF-1
      receptors containing betagc in the regulation of neurite growth.

PMID- 9006987
TI  - The soluble N-ethylmaleimide-sensitive factor attached protein receptor complex
      in growth cones: molecular aspects of the axon terminal development.
AB  - Soluble N-ethylmaleimide-sensitive factor attached protein (SNAP) receptor
      (SNARE) mechanisms are thought to be involved in two important processes in
      axonal growth cones: (1) membrane expansion for axonal growth and (2) vesicular
      membrane fusion for mature synaptic transmission. We investigated the
      localization and interactions among the proteins involved in SNARE complex
      formation in isolated growth cone particles (GCP) from forebrain. We demonstrated
      that the SNARE complex is present in GCPs morphologically without synaptic
      vesicles (SVs) and associated with growth cone vesicles. However, the apparently
      SV-free GCP was lacking in the regulatory mechanisms inhibiting SNARE complex
      formation proposed in SV fusion, i.e., the association of synaptotagmin with the
      SNARE complex, and vesicle-associated membrane protein (VAMP)-synaptophysin
      complex formation. The core components of the SNARE complex (syntaxin, SNAP-25,
      and VAMP) accumulated for several days before postnatal day 7, when SVs first
      appeared, and preceded the accumulation of marker proteins such as synaptophysin,
      SV2, and V-ATPase. Our present results suggest that the SNARE mechanism for
      vesicular transmitter release is not fully functional in growth cones before the
      appearance of SVs, but the SNARE mechanism is working for membrane expansion in
      growth cones, which supports our recent report. We concluded that the regulation
      of the SNARE complex in growth cones is different from that in mature presynaptic
      terminals and that this switching may be one of the key steps in development from
      the growth cone to the presynaptic terminal.

PMID- 9006988
TI  - Phospholipase C-beta1 is present in the botrysome, an intermediate compartment
      like organelle, and Is regulated by visual experience in cat visual cortex.
AB  - Monoclonal antibody Cat-307 identifies a 165 kDa neuronal protein expressed in
      the cat visual cortex during the period of sensitivity to alterations in visual
      experience (). Dark-rearing, which prolongs the sensitive period, also prolongs
      the expression of the Cat-307 protein. The Cat-307 protein localizes to an
      organelle, here called the botrysome (from the Greek botrys, cluster of grapes),
      that is located between the endoplasmic reticulum (ER) and Golgi apparatus. The
      botrysome is composed of small ring-shaped profiles with electron-dense coats.
      The size and morphology of the rings and their coats are similar to those
      described for ER to Golgi transport vesicles. Biochemically, the Cat-307 protein
      cofractionates with microsomes and partitions with subunits of the coatomer
      proteins that coat ER-to-Golgi transport vesicles. Partial amino acid sequencing
      reveals that the Cat-307 protein is phospholipase C-beta1, the G-protein
      dependent phosphodiesterase that hydrolyses phosphatidylinositol 4,5 biphosphate
      into inositol 1,4,5 triphosphate and diacylglycerol after the stimulation of a
      variety of neurotransmitter receptors at the cell surface. These results suggest
      a role for phospholipase C-beta1 and the botrysome in developmental plasticity
      and provide a possible link between receptor activation at the cell surface and
      protein transport during neuronal development.

PMID- 9006989
TI  - Prism adaptation of reaching movements: specificity for the velocity of reaching.
AB  - Accurate reaching toward a visual target is disturbed after the visual field is
      displaced by prisms but recovers with practice. When the prisms are removed,
      subjects misreach in the direction opposite to the prism displacement
      (aftereffect). The present study demonstrated that the severity of the
      aftereffect depends on the velocity of the movements during and after the visual
      displacement. Trained subjects were required to reach with one of four movement
      durations (<300, approximately 800, approximately 2000, and approximately 5000
      msec) from a fixed starting point to a target that appeared at a random location
      on a tangent screen (400 mm away). The size of the aftereffect was largest when
      the movement after the removal was performed with the same duration as that
      performed with the prisms. It became smaller as the difference in velocity became
      larger. When the contralateral arm was used after visual displacement, the
      aftereffect was never significant. Because the adaptation does not generalize
      across velocities or to the other arm, we infer that the underlying changes occur
      at a later stage in the transformation from visual input to motor output, in
      which not only the direction but also the time-dependent parameters of movements,
      such as velocity, acceleration or force, are represented.

PMID- 9006990
TI  - Experience-dependent developmental plasticity in the optic lobe of Drosophila
      melanogaster.
AB  - Early experience can affect nervous system development in both vertebrate and
      invertebrate animals. We have now demonstrated that visual stimulation modifies
      the size of the optic lobes in the laboratory fruitfly Drosophila melanogaster.
      Monocular deprivation (painting over one eye) decreases the aggregate volume of
      the lamina, medulla, and lobula plate by up to 6%. The laminae of control flies
      kept in complete darkness showed a more robust volume difference that could be as
      much as 30%. An electron microscopy study revealed that the changes in the lamina
      are largely attributable to an increase in the terminals of the photoreceptor
      cell axons. The volume of the lamina increases during the first 24 hr after
      emergence, and it grows more in the light than in darkness. When flies are kept
      in the dark for the first 12 hr of their adult life and are then brought back to
      light for the next 3.5 days, the lamina is almost as small as in flies raised for
      4 d in constant darkness. Twelve hour dark shifts at a later time are less
      effective. This finding suggests a critical period for lamina development during
      day 1 of the adult. The lamina depends on visual stimulation to maintain its size
      during the first 5 d after emergence. Dark-rearing for 1 d or more at any stage
      during that period decreases its volume to the level of flies raised in constant
      darkness. A lamina that is once reduced in size seems not to recover.

PMID- 9006991
TI  - A five minute experience in the elevated plus-maze alters the state of the
      benzodiazepine receptor in the dorsal raphe nucleus.
AB  - A single 5 min exposure to the elevated plus-maze test of anxiety renders animals
      insensitive to the anxiolytic effects of the benzodiazepines in this test. The
      purpose of the present experiments was to explore whether this phenomenon
      resulted from a change in the functional state of benzodiazepine receptors in the
      dorsal raphe nucleus. The benzodiazepine receptor agonist midazolam (0.5, 1, and
      2 microg) and antagonist flumazenil (100 and 500 ng) were directly administered
      to the dorsal raphe nucleus in rats either naive to, or with one previous 5 min
      exposure of, the elevated plus-maze. In naive rats, midazolam produced
      significant anxiolytic effects at all doses, and flumazenil was silent. In plus
      maze-experienced rats, midazolam no longer had anxiolytic effects in the plus
      maze, but flumazenil did, indicating that the previous experience of the maze had
      changed the state of the benzodiazepine receptor. This changed receptor function
      generalized to the social interaction test. Thus, in naive animals tested in high
      light, midazolam (0.5, 1, and 2 microg) had significant anxiolytic effects and
      flumazenil (100 and 500 ng) was silent, whereas in plus-maze-experienced rats
      both midazolam (1 microg) and flumazenil (500 ng) had significant anxiolytic
      effects. Extensive analysis of locomotor activity in both tests showed that the
      changed responsivity to midazolam could not be explained by habituation, because
      on none of the measures used was there any difference in motor activity scores
      between plus-maze-naive and experienced rats.

PMID- 9006992
TI  - Evoked excitability changes at the terminals of midlumbar premotor interneurons
      in the cat spinal cord.
AB  - We present evidence that the electrical excitability of the terminals of a group
      of spinal premotor interneurons can be increased after stimulation of sensory
      afferents. The interneurons were located in the midlumbar segments of the spinal
      cord and had projections to the lower lumbar motor nuclei. Thresholds for
      antidromic activation of a substantial number of interneurons were reduced after
      electrical stimulation of group II muscle afferents. Several observations suggest
      that the excitability changes are unlikely to have arisen from electrotonic
      spread of depolarization from the interneuron soma to its terminals or by
      environmental changes in the vicinity of the terminals related to neuronal
      activity. A particularly interesting possibility is that the excitability of the
      central terminals of the interneurons is increased because they are depolarized
      by a mechanism similar to that acting at the terminals of primary sensory
      afferents (primary afferent depolarization, PAD), which accompanies one type of
      presynaptic inhibition. This type of presynaptic action has been shown in
      premotor interneurons in the lamprey but not in the mammalian spinal cord. From
      our observations the organization of the systems generating excitability changes
      at the interneuron terminals seem in general to parallel the organization of the
      systems generating PAD at afferent terminals, raising the possibility that common
      principles might underlie the operation of this form of presynaptic control.

PMID- 9006993
TI  - The role of internal models in motion planning and control: evidence from grip
      force adjustments during movements of hand-held loads.
AB  - We investigated the issue of whether or not the CNS makes use of an internal
      model of the motor apparatus in planning and controlling arm movements. In
      particular, we tested the ability of subjects to predict different hand-held
      loads by examining grip force adjustments used to stabilize the load in the hand
      during arm movements. Subjects grasped a manipulandum using a precision grip with
      the tips of the thumb and index finger on either side. The grip force (normal to
      the contact surfaces) and the load force (tangential to the surfaces) were
      measured, along with the trajectory of the hand. The manipulandum was attached to
      two servo-controlled linear motors used to create inertial and viscous loads as
      well as a composite load, including inertial, viscous, and elastic components.
      The form of the hand trajectory was independent of load for some subjects but
      varied systematically across load conditions in others. Nevertheless, under all
      load conditions and in all subjects, grip force was modulated in parallel with,
      and thus anticipated, fluctuations in load force despite the marked variation in
      the form of the load function. This indicates that the CNS is able to predict the
      load force and the kinematics of hand movement on which the load depends. We
      suggest this prediction is based on an internal model of the motor apparatus and
      external load and is used to determine the grip forces required to stabilize the
      load.

PMID- 9006994
TI  - Toxicity evaluation of waters from a tributary of the River Po using the 7-Day
      Ceriodaphnia dubia test.
AB  - Seven-day toxicity tests with Ceriodaphnia dubia were used to assess ambient
      water toxicity in the River Lambro, a tributary of the River Po, and in the
      corresponding stretch of the main river located downstream from their confluence.
      About once a month, toxicity tests were conducted on water samples of the River
      Lambro, using as dilution water the water of the main river collected upstream
      from the confluence. With a lower frequency, the downstream stretch of the River
      Po was tested for ambient toxicity at four sites located at 6, 11, 16, and 21 km
      from the emission of the tributary. The River Lambro demonstrated variable
      toxicity in different time periods, although the most frequent effects were
      sublethal, on both reproduction and growth. Ammonia, nickel, and zinc can be
      indicated as possible toxicants. Acute toxic effects to C. dubia were observed
      with spring samples only, when the action of some pesticides, likely
      insecticides, have to be taken into account. Tests conducted on downstream water
      gave limited results, seemingly because the dilution capacity of the River Po
      reduced Lambro toxicity to a level close to and often below the detection limit
      of the 7-day test. Accordingly, toxic effects at downstream sites could only be
      observed on the growth of C. dubia, which was found to be the most sensitive
      endpoint. Fairly good agreement was found between predictions based on toxicity
      tests of the River Lambro and the effects observed for downstream samples.

PMID- 9006995
TI  - A scanning electron microscope investigation of the effects of pollutants on the
      hepatopancreatic ceca of Gammarus pulex (L.).
AB  - Scanning electron microscope studies were performed on the peripheral muscle
      network (myoepithelium) of the hepatopancreatic ceca of Gammarus pulex (L.)
      exposed to lindane, copper, or 3, 4-dichloroaniline (3,4-DCA) for a 24-hr period.
      The structural integrity of the myoepithelium of gammarids from control and test
      treatments was assessed using semiquantitative techniques. The lowest observed
      effect concentrations for structural changes were determined as 29.8 microg liter
      1 lindane, 55 microg liter-1 copper, and 8.7 mg liter-1 3,4-DCA. The sensitivity
      of the bioassay and the significance of the morphological changes observed in the
      hepatopancreatic ceca of G. pulex are discussed.

PMID- 9006996
TI  - Effects of diazinon exposure on cholinesterase activity in different tissues of
      European eel (Anguilla anguilla).
AB  - Cholinesterase (ChE) activity was measured in brain, plasma, and whole eye of
      Anguilla anguilla experimentally exposed to a sublethal concentration of 0.042
      mg/liter (0.50 of the 96-hr LC50) of the organophosphorous pesticide diazinon.
      Whole eye was the tissue which revealed higher values of ChE activity (8.17
      micromol/min/g) in nonexposed animals. Brain, plasma, and whole eye ChE activity
      of A. anguilla was inhibited at 6, 24, 48, 72, and 96 hr of diazinon exposure.
      Pesticide induced significant inhibitory effects on the ChE activity of this
      species ranging from >70% inhibition in brain tissue to >90% in plasma samples.
      Brain and plasma presented technical difficulties in their collection. Due to its
      ease of collection, high ChE activity levels, and sensitivity to ChE pesticide
      inhibition, the use of whole eye is recommended for post-mortem ChE analysis in
      A. anguilla.

PMID- 9006997
TI  - Availability and persistence of isoproturon under field and laboratory
      conditions.
AB  - Field and laboratory tests were conducted to investigate the disappearance and
      decrease in availability of the herbicide isoproturon in soil with time.
      Monitoring the fate of 14C-labeled isoproturon gave the persistence of the
      herbicide under different conditions. The calculated half-life (DT50) of the
      extractable parent product was close to 19 days for the two experiments, whereas
      half-lives of exhaustive extractable 14C-residues averaged 22 days under
      controlled conditions versus 48 days in the field. Moreover, if nonextractable
      14C-residues were taken into account in estimating isoproturon fate, the DT50 of
      radioactive residues in soil (extractable parent and degradation products +
      nonextractable residues) reached 1 to 1.4 years under field and controlled
      conditions, respectively. The variability of disappearance rates for the
      different kinds of residues is discussed within a wider definition of
      persistence.

PMID- 9006998
TI  - Toxicity identification evaluation of Lake Orta (Northern Italy) sediments using
      the Microtox system.
AB  - Pore waters extracted by centrifugation from Lake Orta (Northern Italy) sediments
      were studied with a modified Toxicity Identification Evaluation (TIE) procedure
      using the Microtox bacterial luminescence toxicity test system. The most toxic
      pore water samples were from stations near a rayon factory, known as a source of
      copper and ammonium discharges. The TIE manipulations used were filtration, EDTA
      chelation, and C18 solid-phase resin adsorption. The most effective treatments to
      remove toxicity were the EDTA and C18, indicating that both metals and nonpolar
      organic compounds contribute to the observed toxicity.

PMID- 9006999
TI  - Use of the lethal body burden in the evaluation of mixture toxicity.
AB  - In many mixtures of xenobiotics in the field situation, narcosis is the
      predominant mechanism of toxic action. Earlier studies have found that narcotic
      chemicals are additive based on exposure concentration. In this study it is
      revealed that the narcotic chemicals 1,2- and 1,4-dichlorobenzene are additive on
      a lethal body burden level. This applicability of the lethal body burden in risk
      assessment of mixtures of unknown chemicals is discussed, and it is compared with
      other methods of managing mixtures of unknown chemical composition.

PMID- 9007000
TI  - Bioaccumulation of heavy metals by aquatic macrophytes around Wroclaw, Poland.
AB  - Studies were made of heavy metal accumulation in aquatic macrophytes growing in
      streams and ponds around Wroclaw, Poland, partly affected by atmospheric
      pollution, effluents of chemical factories, and groundwater contaminated by
      slagdumps from a smelter and power station. The highest concentrations of Cd, Co,
      Cr, Cu, Hg, Ni, Pb, and Zn in surface water and aquatic macrophytes surpass the
      average values established for background reference sites. Significant positive
      correlations were found between Cu contents in water and Cu, Cd, and Zn contents
      in plants, between Cu and Cd in plants, between Co and Ni in plants, between Ni
      contents in water and Ni and Cu contents in plants, between Zn in water and Cu in
      plants, and between Cd and Ni in plants. Negative correlations were found between
      Cd contents in water and Zn contents in plants, between Co in water and Cd in
      plants, and between Zn in water and Co in plants. Experiments with the liverwort
      Scapania undulata originating from a clean, forested, mountain stream and
      cultivated in solutions containing 70-100% sewage from a chemical factory
      demonstrated an increase in lead content (85 times in 100% sewage and 58 times in
      70% sewage) and in mercury content (40 times in 100% sewage and 20 times in 70%
      sewage), and also an increase in contents of Cd, Cr, Cu, and Ni. Exposure to 70%
      sewage concentration during the 14 days of the experiment may be recognized as
      harmless for S. undulata, so this liverwort could be used in biotechnical
      purification of water.

PMID- 9007001
TI  - Regional variation in As, Cu, Hg, and Se and interaction between them.
AB  - A comparative survey of trace elements in hair samples from three different
      regions of the world was carried out. The concentrations of the same trace
      elements in tissues from infants and adults from Glasgow are also presented. It
      was found that the Se levels in hair samples from Iceland are significantly lower
      than the levels found for the Glasgow area. The level of Hg was in the same range
      as that for the Glasgow area and the As level is much lower in Iceland.
      Comparison of the levels of Hg, As, and Se in hair samples from Iran and Glasgow
      revealed significantly lower levels of these trace elements in samples from Iran,
      but the Cu levels were similar. Comparison of adult and infant levels of Se and
      Cu revealed fetal storage of Cu in the livers of infants. Arsenic levels were
      higher in adult tissues. In the study of the interaction among trace elements in
      human tissues, a positive correlation between Hg and Cu in liver samples from the
      Glasgow area and hair samples from Iran was found. A positive correlation between
      Se and As was also found in spleen and lung tissues.

PMID- 9007003
TI  - New possible molluscicides from Calendula micrantha officinalis and Ammi majus.
      II. Molluscicidal, physiological, and egg-laying effects against Biomphalaria
      alexandrina and Bulinus truncatus.
AB  - In the present study, the effects of CuSo4 and crude extracts of the different
      parts of Calendula micrantha officinalis and Ammi majus, i. e., leaves, stems,
      roots, and flowers, on adult Biomphalaria alexandrina and Bulinus truncatus were
      investigated. Generally, leaves and flowers of both plants exhibited marked
      potency in killing the snail vectors of schistosomiasis. The recorded LC50 and
      LC90 values showed that C. officinalis was more toxic to both snails than A.
      majus, and B. truncatus are more sensitive to the extracts of both plants than B.
      alexandrina. Snails that are produced from snails previously exposed to low doses
      were more sensitive to the tested extracts, which may give primary indication of
      no possibility of inherited resistance. Moreover, prolonged exposure to the
      sublethal concentrations of A. majus have a definite lethal effect on the egg
      laying and longevity of both snails. Also, treatment with sublethal doses of both
      plants clearly inhibited the transaminase activity (ALAT, ASAT), diminished the
      total protein content, and increased markedly total lipid contents in the
      hemolymph of both snails.

PMID- 9007002
TI  - In vitro activities in mussel hemocytes as biomarkers of environmental quality: a
      case study in the Abra Estuary (Biscay Bay).
AB  - Mussels, Mytilus galloprovincialis, were collected from six coastal sites of
      dissimilar water quality (Zierbena, Santurtzi, Arrigunaga, Galea, Menakoz, and
      Plentzia) at Biscay Bay in September 1991, January 1992, June 1992, and September
      1992. The extent of hemocyte infiltration in connective tissue of the digestive
      gland was quantified by stereology on histological sections in terms of volume
      density of hemocytes (HVD). HVD was elevated in mussels collected from Plentzia
      (the less polluted site) in January 1992 and September 1992, while such increases
      occurred in January 1992 in Santurtzi and Arrigunaga and in September 1991 and
      September 1992 in Galea. Conversely, HVD was reduced in Arrigunaga in September
      1991 and in Galea in January 1992. Moreover, HVD was kept unchanged through the
      year in mussels collected from Menakoz and Zierbena. On the basis of this
      preliminary in vivo study, hemocytic activities of mussels collected in September
      1994 from Arrigunaga and Plentzia were further investigated by means of four in
      vitro immunotoxicity assays: (a) the trypan blue exclusion assay, indicative of
      cell viability; (b) the zymosan phagocytosis assay, indicative of phagocytic
      activity; (c) the diaminobenzidine-manganese (DAB-Mn2+) oxidation assay for
      estimating reactive oxygen intermediate (ROI) production; and (d) the neutral red
      (NR) uptake assay, indicative of endocytic ability. These in vitro tests
      indicated some significant differences between Plentzia and Arrigunaga. Hemocytes
      from mussels collected in Plentzia exhibited a higher capability to phagocytose
      zymosan while, conversely, hemocytes from mussels collected in Arrigunaga
      endocytosed more NR and produced more ROI under nonstimulated conditions. These
      differences in the in vitro hemocytic activities of mussels from Plentzia
      (nonpolluted) and Arrigunaga (moderately polluted) suggest that in vitro assays
      may be used as biomarkers of environmental quality in coastal and estuarine
      areas.

PMID- 9007004
TI  - Deltamethrin multifactorial activity toward carp larva mobility related to
      calcium, humic acids, and pH.
AB  - The toxicity of pyrethroid insecticide deltamethrin was assessed by the "escaping
      capability" of carp larvae out of a trap. Mobility was tested after 1, 4, and 12
      hr exposure to eight deltamethrin concentrations in standard water and after 24
      hr exposure to seven deltamethrin concentrations in 18 media derived from the
      combinations of pH levels of 6.9, 7.8, 9.0, calcium concentrations of 2 . 10(-4)
      and 2 . 10(-2) M, and humic acid concentrations on 0, 5 and 100 mg/liter. In
      standard water, a 1-hr exposure at 4 microg/liter deltamethrin increased the
      mobility, while a 4-hr 32 microg/liter exposure decreased it. After 24 hr without
      deltamethrin, mobility was reduced at pH 6.9 and 7.8 and 2 . 10(-4) M calcium. It
      was also reduced in 100 mg/liter humic acids, especially when the former pH and
      calcium conditions were used. Humic acid effects could partly result from a
      calcium concentration reduction in water, and darkness due to humic acid
      coloration could play a minor role. Increasing humic acid concentration, calcium
      concentration, and pH reduced deltamethrin activity. In 0 or 5 mg/liter humic
      acids the No Observed Effect Concentration was 1 microg/liter, and in 100
      mg/liter humic acid it was 2 microg/liter. Compared to previous results on
      deltamethrin-induced lethality, the escape test appeared less reproducible, but
      was 2 or 4 times more sensitive.

PMID- 9007005
TI  - Cadmium interaction with essential metals (Zn, Cu, Fe), metabolism
      metallothionein, and ceruloplasmin in pregnant rats and fetuses.
AB  - Cadmium administered to rats per os is accumulated in the duodenal mucosa in the
      form of metallothionein (MT). Therefore, this toxic metal can influence the
      efficiency of essential metal absorption, especially their concentration in the
      maternal organism, which plays an essential role during fetal development. The
      aim of this study is to elucidate the mechanism of the origin of Zn, Cu, and Fe
      deficiency in fetal rat livers after maternal exposure to cadmium in drinking
      water and to investigate the roles of MT and ceruloplasmin (Cp) in this
      phenomenon. Cadmium was given to pregnant dams exposed for 0-20 days of gestation
      in drinking water at concentrations of 6. 25-100 microg Cd/ml. After cessation of
      exposure, at the lowest dose, a decrease in Cu and Fe concentrations in the
      duodenal mucosa was found. Simultaneously, diminution in concentration of two
      cited metals and Cp activity in serum of dam blood was noted. The lowest dose of
      cadmium developed a drop tendency in microsomal fetal liver iron. Significant
      correlations were observed between fetal liver Cu contents and Cp activity in
      serum of dams and Cu concentrations in serum of dams. Diminished Cp activity in
      serum of dams is related to reduced availability of Cu and Fe in fetuses. In
      conclusion, it is suggested that the mechanism of Cu and Fe deficit content in
      fetuses is based on the diminution of absorption of these metals by dam
      intestines exposed to cadmium on the reduction of metal concentrations in blood
      serum and, in consequence, their decreasing availability in fetuses.

PMID- 9007006
TI  - Cytotoxicity and mutagenicity of 2,4,6-trinitrotoluene and its metabolites.
AB  - Composting has been advocated and is being used as an economical method for
      remediating 2,4,6-trinitrotoluene (TNT)-contaminated soils. However, evidence
      suggests that TNT is transformed into products of unknown toxicity during the
      process. This study was undertaken to examine the in vitro cytotoxicity and
      mutagenicity of TNT and several of its degradation products/metabolites. TNT was
      equally cytotoxic to H4IIE cells and Chinese hamster ovary-K1 (CHO) cells (LC50
      of 4 g/ml vs 24 microg/ml, with overlapping 95% prediction intervals), indicating
      that TNT does not need to be metabolized to exhibit cytotoxicity. Four
      metabolites studied, 4-hydroxylamino-2,6-dinitrotoluene; 2-amino-4,6
      dinitrotoluene; 4,4',6,6'-tetranitro-2,2'-azoxytoluene; and 2,2',6,6'-tetranitro
      4, 4'-azoxytoluene, were equally cytotoxic to both H4IIE and CHO cells. The LC50s
      were in the 3- to 18-microg/ml range and were not significantly different from
      TNT cytotoxicity in both cell lines. 4-Amino-2,6-dinitrotoluene (4-A) was
      moderately less cytotoxic than TNT to H4IIE cells, but was noncytotoxic to CHO
      cells. This result indicates that 4-A is metabolized to a cytotoxic compound.
      Both TNT and its metabolites exhibited only slight mutagenicity at high doses in
      one or both of the mutagenicity assays. While composting may reduce the levels of
      TNT in composted material, the hazard associated with TNT-contaminated soils is
      probably lower, but still uncertain.

PMID- 9007007
TI  - Effects of age and coion (K+ and Na+) on the toxicity of thiocyanate to rainbow
      trout (Oncorhynchus mykiss) during pulse or continuous exposure.
AB  - Thiocyanate (SCN-) is released to the aquatic environment as a result of the
      treatment of cyanide-bearing wastes from precious-metal mining activity. During
      continuous exposure alevin rainbow trout (1- and 10-day-old) were approximately
      90% more tolerant of SCN- than juveniles (2-month-old). Pulse exposure of alevins
      for periods > or = 48 hr were required before postexposure stress reduced
      tolerance (by approximately 30%) in the 24-hr period following exposure. In
      contrast, stressing of juveniles after exposures of > or= 9 hr consistently
      reduced tolerance by approximately 60%. While coion (K+ or Na+ for SCN- derived
      from either KSCN or NaSCN) had no influence on SCN- toxicity for alevins,
      juveniles exhibited reduced tolerance in the presence on Na+. Although sudden
      death syndrome was apparent in juveniles, none occurred with alevins. Overall,
      juveniles were less tolerant of SCN- than alevins, possibly because of the
      enhanced efficiency of SCN- uptake by gill respiration versus the predominantly
      vitelline membrane respiration of alevins.

PMID- 9007008
TI  - Recipient of the Berlex Clinical Oncology Research Fellowship for 1996/1997

PMID- 9007009
TI  - Instability of Rts1 (drug-resistant factor) replicon: stabilization by DNA
      fragments derived from Rts1.
AB  - Rts1 is a large naturally occurring plasmid which has a kanamycin resistance gene
      and exhibits various temperature-sensitive phenotypes. A smaller derivative of
      plasmid, pOK, contains the Rts1 replicon and the kanamycin resistance gene of
      Rts1. This plasmid, pOK, is much more unstable than Rts1 at 42.5 degrees C. A DNA
      fragment, G3, 1590 nucleotides long from Rts1 DNA, stabilized pOK completely at
      42.5 degrees C but only in the cis configuration. G3 did not change the copy
      number of pOK. The pOK derivative containing G3 was destabilized by the presence
      of a compatible plasmid containing G3. G3 has four inverted repeats, two 14-base
      direct repeats, and three ORFs. Smaller fragment of G3 also had a stabilization
      effect and these studies showed that the ORF does not play any role in
      stabilization.

PMID- 9007010
TI  - Suggestions as to quantitative measurements of plasmid loss.
AB  - Suggestions are made for the estimation of plasmid loss rates in bacterial
      populations that multiply by binary fission. The plasmid loss rate is defined as
      the probability of a division of a plasmid-carrying individual giving birth to
      one plasmid-free and one plasmid-carrying daughter cell. The unit of time is
      consequently the interdivision time for plasmid-carrying individuals. The
      cautions that have to be taken when the population is cultivated in serial
      transfer (the usual stability experiment) are discussed.

PMID- 9007011
TI  - Estimation of plasmid loss rates in bacterial populations with a reference to the
      reproducibility of stability experiments.
AB  - Two methods for estimation of plasmid loss rates were tested on data obtained
      from traditional (serial transfer) stability experiments. The first method was
      based on the assumption that the plasmid does not inhibit the growth of its host,
      whereas the second method takes differences in the interdivision time of plasmid
      free and plasmid-carrying cells into account. In the cases where the loss rate is
      high and the plasmid does not exert strong growth inhibition, the estimates
      appear very reliable. When the plasmid loss rate is small and the plasmid exerts
      inhibition of growth to its host, the experimental design becomes unreliable.

PMID- 9007012
TI  - Wild-type strains of Dictyostelium discoideum can be transformed using a novel
      selection cassette driven by the promoter of the ribosomal V18 gene.
AB  - Almost all methods for transformation of the social ameba Dictyostelium
      discoideum rely on axenic growth, that is, growth in a synthetic medium, for at
      least part of the procedure. Axenic growth requires several mutations. Here we
      describe a procedure that can be used to transform wild-type strains which are
      able to grow only on the natural food source, bacteria. The method relies on a
      new selection cassette driven by the V18 promoter, a promoter that we show is
      substantially more active during growth on bacteria than the actin-6 promoter,
      which is widely used for axenic transformation. The procedure gives
      transformation frequencies of about 10(-5) with both strains Ax2 (capable of
      axenic growth) and NC4 (capable of growth only on bacteria). Using this vector,
      we have obtained NC4 strains carrying several beta-galactosidase reporter
      cassettes. Our vector can also be used in axenic transformations.

PMID- 9007013
TI  - Characterization of the stable maintenance of the Shigella flexneri plasmid pHS
      2.
AB  - pHS-2 is a 3-kb plasmid originally isolated from Shigella flexneri infections
      associated with reactive arthritis in humans. This plasmid is stably maintained
      in many clinical isolates of Shigella flexneri. The nucleotide sequence of this
      plasmid displays two closely linked regions that may play a role in the
      maintenance of this plasmid. One region consists of a 250-bp locus showing a
      significant homology to the ColE1 cer site. The results indicate that the cer
      like site of pHS-2, like the ColE1 cer site, acts as a recA-independent, site
      specific recombination site involved in the resolution of multimers, requiring
      the presence of the host-encoded factors ArgR, PepA, XerC, and XerD. The second
      region consists of a 36-kDa open reading frame involved in generating resistance
      to the bactericidal effect of complement, which confers a selective advantage to
      cells containing this sequence. The results also indicate that pHS-2 can
      replicate in another species of Enterobacteriaceae (Escherichia coli) and is
      mobilized by the F plasmid.

PMID- 9007014
TI  - Two related rolling circle replication plasmids from salt-tolerant bacteria.
AB  - In a range of salt-tolerant bacteria isolated from soil, rhizosphere, and
      phyloplane, cross-hybridization tests revealed a group of seven plasmids which
      were chosen for further study. Two plasmids (pSH1418 and pSH1451) were picked as
      representative examples of the two related subgroups. Restriction mapping and
      Southern blotting identified a region common to the two plasmids which later was
      identified as encoding the replication functions. We were unable to join these
      plasmids to high-copy-number vectors but this was possible with low-copy-number
      IncP vectors. In Escherichia coli, cloned plasmids pSH1418 and pSH1451 conferred
      salt tolerance but the phenotype was unstable, with the loss of salt tolerance
      apparently being correlated with structural instability of the plasmid DNA.
      Plasmid pSH1451 was sequenced and shown to be closely related to RCR plasmids of
      Gram-positive bacteria. The host of this plasmid was classified as Bacillus
      pumilus by rDNA typing and lipid profiling by gas chromatography. A number of
      open reading frames (orfs) which could code for salt tolerance or other functions
      were identified in the plasmid sequence. Sequence similarity to previously
      sequenced genes suggested that the products of orf4 and orf5 may work together to
      transport a molecule such as aspartate ion that may promote osmotolerance.

PMID- 9007015
TI  - Analyses of traA, int-Tn, and xis-Tn mutations in the conjugative transposon
      Tn916 in Enterococcus faecalis.
AB  - The conjugative transposon Tn916 moves intercellularly via an excision/insertion
      mechanism that involves products of int-Tn and xis-Tn. Tn5-insertion mutations in
      these genes were found to be complemented in an Enterococcus faecalis host by
      specific coresident transposons harboring the corresponding wild-type allele. A
      determinant designated traA, partially overlapping and divergently transcribed
      from xis-Tn, is thought to encode a key positively acting regulatory protein
      needed for expression of conjugation functions. This locus was also shown to
      express a trans-acting product.

PMID- 9007016
TI  - Phylogenetic analysis of North American Rhagoletis (Diptera: Tephritidae) and
      related genera using mitochondrial DNA sequence data.
AB  - Partial sequences (approximately 850 bp) of the mitochondrial 16S ribosomal RNA
      gene were determined for 21 members of the fruit fly genus Rhagoletis and 6
      related tephritid taxa by sequencing DNA amplified by the polymerase chain
      reaction. Sequences were highly A + T rich, with an average G + C content of
      19.2%. Sequence divergence ranged from 0 to 11.7% among the included taxa.
      Sequences were used to reconstruct the phylogeny of this group of flies with
      neighbor-joining and maximum parsimony methods. A group of 18 North American
      Rhagoletis species formed a monophyletic clade, and three morphologically based
      species groups were identified with strong statistical support. Relationships
      among the species groups were partially resolved. The tabellaria species group
      appears to be paraphyletic with respect to the pomonella species group, in
      contrast to previous allozyme analyses that united the cingulata and pomonella
      groups. The relations of the North American clade to other genera within the
      tribe Carpomyini were not clearly resolved. Rhagoletis striatella, a North
      American species that uses members of the tomato family (Solanaceae) as a larval
      host, may be more closely associated with South American Rhagoletis species and
      related genera than with the other North American Rhagoletis species.

PMID- 9007017
TI  - Molecular phylogenetic study of Tephritidae (Insecta: Diptera) using partial
      sequences of the mitochondrial 16S ribosomal DNA.
AB  - We analyzed sequence data from 925 base pairs within the mitochondrial 16S
      ribosomal DNA from 34 tephritid species and two outgroup taxa. DNA sequences were
      amplified by the polymerase chain reaction and sequenced by the dideoxy chain
      termination method. Patterns of nucleotide composition and substitution were
      assessed based on sequence comparison. Phylogenetic relationships among the
      included taxa were inferred using neighbor-joining and maximum parsimony methods.
      The trees were congruent with the morphological classification and suggested the
      following phylogenetic relationships: (1) monophyly of the tribe Trypetini, s.
      str., excluding Parastenopa; (2) a possible sister group relationship between
      Platyparea and the subfamily Tephritinae; (3) a sister group relationship between
      Hexachaeta and the tribe Toxotrypanini; (4) monophyly of the Dacinae and possible
      relationship of Oedicarena to this subfamily; (5) monophyly of the tribe
      Adramini; and (6) the nonmonophyletic nature of the genus Rhagoletis. We propose
      that the 16S rDNA shows great promise for helping to create a phylogenetically
      based higher classification of the Tephritidae.

PMID- 9007018
TI  - Phylogeny of the genus Rhagoletis (Diptera: Tephritidae) inferred from DNA
      sequences of mitochondrial cytochrome oxidase II.
AB  - Despite a considerable literature describing the biology of flies in the
      tephritid genus Rhagoletis, the phylogenetic relationships of the more than 60
      species classified within the genus are not well resolved. Knowledge of these
      relationships is important, not only in terms of obtaining information that will
      be useful for the control of Rhagoletis where it is an agricultural pest, but
      also in determining what role host plant shifts have played in the generation of
      Rhagoletis species diversity, a focal point in debate over the role of sympatric
      speciation in the evolutionary process. In this paper, the phylogenetic history
      of 28 Rhagoletis species and 6 species in related tephritid genera is inferred
      from nucleotide sequences of subunit II of the mitochondrial cytochrome oxidase
      (COII) gene and the adjacent tRNALeu/COII intergenic region. Analyses of the data
      using distance and character-state approaches suggest the following: (i) the
      genus Rhagoletis as currently defined is not monophyletic; (ii) the 5
      predominantly North American Rhagoletis species groups do constitute a
      monophyletic assemblage; (iii) the North American species groups form 2 clades, 1
      consisting of taxa in the R. pomonella and R. tabellaria species groups (plus R.
      fausta), and the other consisting of taxa in the R. ribicola, R. cingulata, and
      R. suavis species groups; and (iv) the origin(s) of the North American species
      groups is obscure, as evidenced by the recovery of clades containing both
      Palearctic and Neotropical taxa. Areas of congruence and conflict with published
      phylogenies of Rhagoletis are examined and, while many areas of conflict may be
      due to an insufficient number of characters or incomplete taxon sampling, we
      cannot discount the possibility that real differences exist between the
      Rhagoletis mitochondrial DNA gene tree and the Rhagoletis species tree.

PMID- 9007019
TI  - Phylogeny of cephalopods inferred from mitochondrial DNA sequences.
AB  - Sequences of partial mitochondrial cytochrome oxidase III gene (533 bp) were
      obtained for 17 species of cephalopods, 14 decapods, 2 octopods, and 1
      vampyromorph. This study aimed to: (1) compare partial COII and COIII amino acid
      sequences of three species of cephalopods with other invertebrates in terms of
      base composition and phylogenetic relationships. Cephalopod sequences are closer
      to Katharina tunicata sequences than to Mytilus edulis (marine bivalve) and
      Albinaria turrita (terrestrial gastropod); (2) investigate the phylogenetic
      relationships among cephalopods. Nucleotides as well as amino acid sequence
      variations of a COIII fragment were examined with parsimony and distance methods.
      Our data confirm the monophyly of the Decapoda and of each family. A high
      hierarchical rank for sepiolids, already suggested by other authors, appears
      justified. The order Sepioidea comprising five families should be abandoned, with
      Spirula being excluded. The surprising position of Idiosepius as the sister group
      of some oegopsids and not of sepioids or sepiolids is confirmed. Vampyroteuthis
      is the sister group of octopods. However, the data do not allow resolution of the
      phylogenetic relationships between the orders of Decapoda; consequently we
      suspect a rapid radiation.

PMID- 9007021
TI  - A physiological and molecular analysis of the genus Nicotiana.
AB  - An analysis of the evolution of the genus Nicotiana was carried out with
      physiological and molecular tools. The capacity of explants from seedlings of
      several species of Nicotiana to differentiate roots or shoots or to habituate was
      used to ascertain whether the in vitro behavior of species has a nonrandom
      distribution in the genus. The results obtained allowed us to identify two groups
      of species, one root-forming prone composed of Paniculatae (subgenus Rustica) and
      the other composed of Alatae, Repandae, and Noctiflorae (subgenus Petunioides),
      with a major tendency toward the production of shoots. Habituation capacity was
      characteristic of species randomly distributed throughout the phylogenetic tree.
      These data suggest fixation throughout the evolution of coadapted gene complexes
      (hormone-related genes) involved in the control of developmental processes.
      RAPDs, on the other hand, used as molecular markers for the clustering of related
      species, seem entirely coherent both with classical morphological and
      karyological studies and with in vitro physiological methods, supporting an early
      subdivision of the whole genus into two diverging developmental patterns.

PMID- 9007020
TI  - Phylogenetic relationships of chelid turtles (Pleurodira: Chelidae) based on
      mitochondrial 12S rRNA gene sequence variation.
AB  - Conflicting phylogenies have been proposed for the Chelidae (Testudines:
      Pleurodira), a family of side-necked turtles found only in Australasia and South
      America. Sequence data from the mitochondrial 12S rRNA gene were used to test
      these phylogenies. In total, 411 nucleotides were sequenced for each of 16 chelid
      species, including all 11 recognized chelid genera and, as outgroups, 5 genera of
      Pelomedusidae (Testudines: Pleurodira). Analyses using parsimony and neighbor
      joining algorithms strongly support the division of Australian Chelidae into the
      three monophyletic groups initially suggested by Burbidge et al. (1974; Copeia 2:
      392-409): Chelodina (bootstrap value 99%), the Emydura group (87%), and
      Pseudemydura. The analyses suggest that the Australian chelids are a monophyletic
      lineage (64%), with the Australian long-necked turtles, Chelodina, more closely
      related to the Australian short-necked chelids than to the long-necked South
      American species. These relationships are in contrast to those of Gaffney (1977;
      Am. Mus. Novitates 2620: 1-28). The species of Australian long-necked chelids
      consistently form a monophyletic clade, with Chelodina longicollis and Chelodina
      oblonga as sister taxa. The data failed to resolve relationships among the
      Australian short-necked taxa: Emydura, the Elseya latisternum group, the Elseya
      dentata group, Rheodytes, and Elusor. Unlike Gaffney (1977), we find some weak
      support (58%) for Pseudemydura as the closest relative of the other Australian
      short-necked taxa. With the exception of Hydromedusa, the South American taxa are
      monophyletic and the subgenera of Phrynops are paraphyletic.

PMID- 9007022
TI  - Mitochondrial DNA sequence analysis of the masu salmon--phylogeny in the genus
      Oncorhynchus.
AB  - We determined 2162-bp sequences from the mitochondrial genome of the masu salmon
      Oncorhynchus masou masou, chum salmon Oncorhynchus keta, and Atlantic salmon
      Salmo salar by using polymerase chain reactions. These DNA sequences span from
      the 3' region of the gene for ATPase subunit 6 to the 5' region of the gene for
      NADH dehydrogenase subunit 4L. With the aid of the sequence data from other
      Pacific salmonid species (Thomas and Beckenbach, 1989, J. Mol. Evol. 29: 233
      245), the evolutionary distances among the masu salmon and other species in the
      genus Oncorhynchus were calculated. These evolutionary distances were then used
      to construct a neighbor-joining tree. Further, a maximum parsimony tree was
      constructed. The evolutionary trees that were obtained suggest that masu salmon
      first diverged from the common ancestor of the genus Oncorhynchus.

PMID- 9007023
TI  - Evolution of the Drosophila obscura species group inferred from the Gpdh and Sod
      genes.
AB  - The Drosophila obscura group consists of several dozen Nearctic and Palearctic
      species, with a phylogeny that remains largely unresolved in spite of numerous
      morphological, cytogenetic, and molecular investigations. We have partially
      sequenced two genes, Gpdh (about 1000 bp) and Sod (about 700 bp) in 12-13 species
      and 1 subspecies in order to settle the issues. Difficulties in resolving the
      phylogeny emanate from the rapid sequence of successive radiations. Nevertheless,
      the following conclusions are warranted: (1) The Palearctic species include two
      monophyletic subgroups, subobscura (which may be the most ancient clade of the
      whole group) and obscura, plus two other species with unresolved phylogenetic
      positions, D. bifasciata and D. subsilvestris; (2) the Nearctic species form a
      monophyletic group consisting of two monophyletic sister clades, the affinis
      subgroup and the pseudoobscura subgroup. The Palearctic radiation may have
      resulted from adaptation to expanding temperate forests in the Old World. A
      second radiation occurred during the colonization of the deciduous forests of the
      New World by the descendants of a single lineage that soon split into the affinis
      and pseudoobscura subgroups.

PMID- 9007024
TI  - Phylogenetic analysis of nematodes of the genus Pratylenchus using nuclear 26S
      rDNA.
AB  - We used nucleotide sequences of the large subunit ribosomal genes (26S rDNA) to
      examine evolutionary relationships among species of the genus Pratylenchus
      (Order: Tylenchida, Family: Pratylenchidae), commonly known as root-lesion
      nematodes. Ten species of Pratylenchus were studied including, P. penetrans, P.
      crenatus, P. minyus, P. vulnus, P. thornei, P. musicola, P. coffeae, P.
      hexincisus, P. scribneri, and P. brachyurus. The species Hirschmanniella belli,
      Meloidogyne javanica, Heterorhabditis bacteriophora, Nacobbus aberrans,
      Radopholus similis, and Xiphinema index were used as outgroups. Based on
      parsimony analyses of approximately 307 aligned nucleotides of the D3 expansion
      region of the 26S rDNA, it is clear that species of Pratylenchus are a
      paraphyletic assemblage. The outgroup taxon H. belli shares a common ancestor
      with the clade that includes P. vulnus and P. crenatus while N. aberrans and R.
      similis share a common ancestor with 5 other species included in this study.

PMID- 9007025
TI  - Two divergent intragenomic rDNA ITS2 types within a monophyletic lineage of the
      fungus Fusarium are nonorthologous.
AB  - The evolutionary history of the phytopathogenic Gibberella fujikuroi complex of
      Fusarium and related species was investigated by cladistic analysis of DNA
      sequences obtained from multiple unlinked loci. Gene phylogenies inferred from
      the mitochondrial small subunit (mtSSU) rDNA, nuclear 28S rDNA, and beta-tubulin
      gene were generally concordant, providing strong support for a fully resolved
      phylogeny of all biological and most morphological species. Discordance of the
      nuclear rDNA internal transcribed spacer 2 (ITS2) gene tree is due to paralogous
      or xenologous ITS2 sequences. PCR and sequence analysis demonstrated that every
      strain of the ingroup species tested possesses two highly divergent
      nonorthologous ITS2 types designated type I and type II. Only the major ITS2
      type, however, is discernable when PCR products are amplified and sequenced
      directly with conserved primers. The minor ITS2 type was recovered using ITS2
      type-specific PCR primers. Distribution of the major ITS2 type within the species
      lineages exhibits a homoplastic pattern of evolution, thus obscuring true
      phylogenetic relationships. The results suggest that the ancestral ITS2 types may
      have arisen following an ancient interspecific hybridization or gene duplication
      which occurred prior to the evolutionary radiation of the Gibberella fujikuroi
      complex and related species of Fusarium. The results also indicate that current
      morphological-based taxonomic schemes for these fungi are unnatural and a new
      classification is required.

PMID- 9007026
TI  - A molecular phylogeny of Mobile River drainage basin pleurocerid snails
      (Caenogastropoda: Cerithioidea).
AB  - Sequences from the mitochondrial 16S rRNA gene were obtained to construct a
      molecular phylogeny for Mobile River drainage basin pleurocerid snails. Data from
      876 aligned positions generated a single most-parsimonious tree for each of three
      analytical approaches: (1) equal weighting, (2) transversions weighted 2 x
      transitions; and (3) transversions weighted 4 x transitions. Identical topologies
      for the resulting trees depict the genera Elimia and Pleurocera as monophyletic
      sister taxa. The genus Leptoxis is paraphyletic with Leptoxis plicata sister to
      the Elimia + Pleurocera clade. L. taeniata and L. ampla are sister taxa and L.
      picta is the most basal pleurocerid examined. When transversions were weighted
      10x transitions a single most-parsimonious tree was obtained with the only
      topological difference being L. picta depicted as sister to L. taeniata and L.
      ampla and L. plicata is now the most basal pleurocerid examined. Many of the
      Elimia species are closely related, but we await further data before making any
      taxonomic recommendations. L. picta and L. plicata are quite distinct from each
      other and all other pleurocerid species examined. These data serves as an
      important foundation for future studies examining conservation genetics and
      systematics of this diverse and imperiled family.

PMID- 9007027
TI  - Phylogenetic relationships among tick subfamilies (Ixodida: Ixodidae: Argasidae)
      based on the 18S nuclear rDNA gene.
AB  - Phylogenetic relationships among tick subfamilies have been estimated using
      morphological and molecular characters. However, the phylogeny based on a portion
      of the 16S mitochondrial rDNA gene differed from the morphologically based
      phylogeny in a number of important respects. The entire 18S rDNA gene was
      examined in 18 taxa from all tick subfamilies to test the 16S rDNA based
      phylogeny. The 18S phylogeny supports the earlier 16S based phylogeny in placing
      members of Hyalomminae on a common branch with members of the Rhipicephalinae and
      in indicating long branch lengths among soft tick taxa. However, unlike the 16S
      phylogeny, Amblyomminae was monophyletic and members of Haemaphysalinae did not
      arise within Amblyomminae. Argasinae formed a monophyletic group within Argasidae
      and was not a sister taxon of the hard ticks. In most respects, the phylogeny
      based on the 18S rDNA gene resembles the morphologically based phylogeny.

PMID- 9007028
TI  - Ultrastructural characterization of the early changes in intercellular junctions
      in response to cadmium (Cd2+) exposure in LLC-PK1 cells.
AB  - Previous studies have shown that Cd2+ can disrupt the Ca2+-dependent junctions
      between LLC-PK1 cells. The objective of the present studies was to further
      characterize the early junctional effects of Cd2+ in LLC-PK1 cells and to
      identify the initial site of injury. LLC-PK1 cells were grown on permeable
      membrane supports and were exposed to 10 microM Cd2+ from the basolateral
      compartment. The integrity of cell junctions was assessed by light and electron
      microscopy and by measuring the transepithelial electrical resistance. After as
      little as 15 min of Cd2+ exposure, there was an increase in the amount of light
      transmitted between the cells. The transepithelial resistance began to decline by
      30 min and continued to fall until reaching zero after about 6 hr.
      Ultrastructural analysis showed that the initial disruption of cell-cell
      junctions coincided with a decrease in the density of intracellular plaques
      associated with the adhering junctions (zonulae adherens). This effect increased
      with time and paralleled an increase in the space between cells and a change in
      the shape of the cells from squamous to rounded. Sectioning the cells
      horizontally, in a plane parallel to the membrane support, allowed us to see
      large areas of zonulae adherens. Cd2+ caused the formation of gaps within the
      zonulae which increased with time of exposure. No significant changes in most
      occluding junctions (zonulae occludens) were seen until 6-8 hr after Cd2+
      exposure. These results indicate that the adhering junctions and associated
      cytoplasmic components are primary sites of early Cd2+ injury in LLC-PK1 cells
      and they suggest that these effects may result from the interaction of Cd2+ with
      target sites associated with the basolateral cell surface.

PMID- 9007029
TI  - Dose- and route-dependent alterations in metabolism and toxicity of chemical
      compounds in ethanol-treated rats: difference between highly (chloroform) and
      poorly (carbon tetrachloride) metabolized hepatotoxic compounds.
AB  - The dose and route dependency of the metabolism and the toxicity of chloroform
      (CHCl3) and carbon tetrachloride (CCl4) was investigated in ethanol-treated rats.
      Rats that had been kept on either an ethanol (containing ethanol at 2 g/rat/day)
      or a control (containing no ethanol) liquid diet for 3 weeks were challenged with
      CHCl3 or CCl4 by inhalation (0, 50, or 500 ppm x 6 hr), or by p.o. or i.p.
      administration (0, 0.105, or 1.675 mmol/kg). Ethanol consumption, which increased
      the in vitro metabolism of both compounds six- to sevenfold, affected the
      metabolism and toxicity of CCl4 differently from those of CHCl3. Ethanol
      increased the metabolism and toxicity of CHCl3 at 500 ppm only, whereas it
      increased the metabolism and toxicity of CCl4 at either 50 or 500 ppm. In
      addition, the effect of ethanol consumption differed between CHCl3 and CCl4
      depending on the route of administration (p.o. or i.p.) and the dose (0.105 or
      1.675 mmol/kg). For the p.o. route, ethanol increased the metabolism and toxicity
      of both compounds at either dose. For the i.p. route, however, ethanol increased
      the metabolism and toxicity of the high dose of CHCl3 only, but of both CCl4
      doses. The dose- and route-dependent differences in the effect of enzyme
      induction on the metabolism and toxicity between CHCl3 and CCl4 can be explained
      by a supposition that the hepatic blood flow rate-limits the metabolism of a low
      dose of CHCl3 (perfusion-limited metabolism), whereas the metabolic capacity of
      the liver limits the metabolism of CCl4 (capacity-limited metabolism)
      irrespective of dose.

PMID- 9007030
TI  - Nasal cytochrome P450 2A: identification, regional localization, and metabolic
      activity toward hexamethylphosphoramide, a known nasal carcinogen.
AB  - Two members of the cytochrome P450 2A subfamily, CYP2A10 and 2A11, are abundant
      nasal enzymes previously characterized in rabbit olfactory microsomes. Rabbit
      CYP2A is active toward a number of nasal toxicants, including the rat nasal
      procarcinogen hexamethylphosphoramide (HMPA). While P450s immunochemically
      related to the rabbit CYP2As have been detected in rat and human nasal mucosa,
      confirmation of these enzymes as members of the CYP2A subfamily and efforts to
      characterize their ability to bioactivate toxicants have been limited. In the
      present study, the regional distribution and cell-specific expression of CYP2A in
      the rat nasal cavity were examined using an antibody to rabbit CYP2A10/11. In
      sections of the anterior nose, immunoreactive CYP2A was present in ciliated cells
      of the nasal respiratory epithelium and cuboidal epithelial cells of the nasal
      transitional epithelium, but was absent in squamous epithelial cells. The most
      intense immunostaining was observed in the posterior nose. Olfactory
      sustentacular cells and Bowman's gland cells in sections posterior to the nasal
      papilla stained most intensely. Western blot analysis revealed that anti
      CYP2A10/11 recognized a sharp band of approximately 50 kDa in nasal respiratory
      and olfactory microsomes, supporting the premise that the antibody is reacting
      with a cytochrome P450 enzyme. The nasal expression of CYP2A6 mRNA--a member of
      the human CYP2A subfamily having a high degree of homology to rabbit 2A10 and
      2A11--was examined in human surgical patients. Middle turbinectomy tissues-
      largely composed of nasal respiratory epithelia--from 11 patients were analyzed
      for the presence of CYP2A6 using reverse transcription-polymerase chain reaction
      (RT-PCR). Identification of CYP2A6 was confirmed by DNA sequencing of RT-PCR
      products. CYP2A6 mRNA was detected in all of the human samples analyzed. In
      additional experiments, human CYP2A6 metabolized HMPA to formaldehyde, suggesting
      that this compound might cause nasal toxicity in humans. The identification of
      CYP2A cytochromes in rat and human nasal tissues may have important implications
      for risk assessment of inhaled xenobiotics.

PMID- 9007031
TI  - The mechanism for hexachlorocyclohexane-induced cytotoxicity and changes in
      intracellular Ca2+ homeostasis in cultured cerebellar granule neurons is
      different for the gamma- and delta-isomers.
AB  - The cytotoxic action of the delta- and gamma-isomers of hexachlorocyclohexane
      (HCH) as well as their ability to induce changes in intracellular Ca2+
      homeostasis was studied in cultured rat cerebellar granule neurons. Changes in
      the free intracellular Ca2+ concentration ([Ca2+]i) related to Ca2+ influx and
      release from intracellular stores were investigated using, in addition to the
      physiological incubation medium, media without added Ca2+ (nominally Ca2+ free)
      or containing verapamil or dantrolene, drugs which block influx through voltage
      gated Ca2+ channels and release from intracellular stores, respectively.
      Cytotoxicity was monitored using leakage of lactate dehydrogenase (LDH) and
      staining of damaged cells with either trypan blue or propidium iodide. In the
      latter case, when fluorescence microscopy was employed, undamaged cells were
      visualized using the vital stain calcein acetoxymethyl ester (calcein-AM). The
      delta-isomer of HCH was found to be more potent and active as a cytotoxic agent
      than the gamma-isomer (lindane) and it was demonstrated that the moderate
      cytotoxic action of lindane could be ameliorated by dantrolene which on the other
      hand had no effect on cytotoxicity induced by delta-HCH. It was noticed that
      pronounced (50% increase in fluorescence) staining with propidium iodide was
      associated with only a marginal (20%) LDH leakage and staining of only a few
      (<25%) cells with trypan blue. Both delta- and gamma-HCH induced an increase in
      [Ca2+]i which was most pronounced in case of delta-HCH. Analysis of the different
      mechanisms governing the increase in [Ca2+li using dantrolene, verapamil, and
      Ca2+-free medium revealed distinct differences between the two isomers with
      regard to the Ca2+ pools affected. Both isomers stimulated Ca2+ influx through
      voltage-gated Ca2+ channels but only the gamma-isomer affected a Ca2+-dependent,
      dantrolene-sensitive pool. On the other hand, delta-HCH affected mainly a Ca2+
      independent dantrolene-insensitive pool. The finding that delta-HCH was more
      toxic than lindane may be correlated to the differences between the isomers with
      regard to the action on the different Ca2+ pools. Thus, delta-HCH affected
      primarily the dantrolene-insensitive Ca2+ pools which partly reflect influx. On
      the contrary, lindane had little effect on these Ca2+ pools but affected
      primarily dantrolene-sensitive intracellular Ca2+ stores. This may suggest that
      delta-HCH may exert its cytotoxic action by stimulating a large influx of Ca2+
      possibly leading to release of Ca2+ from dantrolene-insensitive stores. In
      contrast, the toxic action of lindane may be primarily related to release of Ca2+
      from the dantrolene-sensitive stores.

PMID- 9007032
TI  - The effects of continuous testosterone exposure on spontaneous and cadmium
      induced tumors in the male Fischer (F344/NCr) rat: loss of testicular response.
AB  - In the rodent testes, cadmium induces severe necrosis followed by chronic
      degeneration. Cadmium is also an effective testicular tumorigen, and a single
      dose produces a high incidence of Leydig cell tumors. The mechanism of tumor
      formation is unknown, but pituitary feedback, i.e., increased luteinizing hormone
      (LH) production due to low circulating androgen, has been implicated in causation
      of proliferative lesions within degenerate, hypofunctioning testes. Thus, the
      effects of androgen replacement on the testicular toxicity of cadmium in Fischer
      (F344/NCr) rats was studied. Groups (n = 50) of 10-week-old rats either received
      testosterone implants that approximate normal circulating levels in castrated
      rats or were left untreated. After 2 weeks of stabilization, rats were given
      either 20 micromol CdCl2/kg, s.c., weekly for the next 5 weeks (total dose 100
      micromol/kg) or saline for a total of four treatment groups (control,
      testosterone alone, testosterone + cadmium, or cadmium alone). Portions of each
      group were killed either 10 weeks after initiation of cadmium exposure (n = 10),
      for assessment of endocrine function, or over the next 2 years (n = 40), for
      assessment of testicular neoplastic lesions. At 10 weeks, cadmium reduced
      circulating testosterone in nonimplanted rats by nearly 80% and induced a marked
      weight loss of the testes (>70%) and sex accessory glands (reflected in a 50%
      reduction in prostate mass). Testosterone implantation restored circulating
      testosterone levels in cadmium-treated rats and prevented Cd-induced weight loss
      of the sex accessory glands but not of the testes. Over 2 years, cadmium alone
      induced a >84% incidence of Leydig cell neoplasia and a >97% incidence of chronic
      degeneration, both significant increases over control rates (60 and 0%,
      respectively). Testosterone implantation abolished both cadmium-induced and
      spontaneously occurring Leydig cell tumors but had no effect on cadmium-induced
      chronic testicular degeneration. Thus cadmium-induced hypofunction of the testes,
      and subsequent loss of circulating testosterone, appears to be a critical aspect
      in cadmium induction of tumors in the rat testes.

PMID- 9007033
TI  - Cochlear protection from carbon monoxide exposure by free radical blockers in the
      guinea pig.
AB  - Acute carbon monoxide exposure produces a significant impairment in high
      frequency auditory sensitivity that can be prevented using the N-methyl-D
      aspartate receptor blocker MK-801. This finding suggests an excitotoxic component
      to carbon monoxide ototoxicity and establishes the potential for free radical
      formation. Free radical scavengers and inhibitors are protective in many organs,
      including the brain and cochlea, during hypoxic events such as
      ischemia/reperfusion and, in the cochlea, during noise exposure. This study
      evaluated the protection afforded by two such agents, phenyl-n-tert-butyl-nitrone
      (PBN), which acts as a general free radical scavenger, and allopurinol, which
      acts as a free radical inhibitor specific to the xanthine oxidase metabolic
      pathway. Guinea pigs were pretreated with PBN (100 mg/kg i.p.), allopurinol (100
      mg/kg i.p.), or saline 1 hr prior to exposure to carbon monoxide (35 ml/kg i.p.)
      or to an equal volume of air. They were monitored at 15, 30, and 60 min after
      carbon monoxide exposure for alterations in compound action potential threshold
      and cochlear microphonic amplitude. The groups receiving carbon monoxide alone
      displayed characteristic compound action potential threshold elevations
      particularly at the higher test frequencies (16-40 kHz), consistent with earlier
      studies; no loss of cochlear microphonic amplitude was exhibited. Both free
      radical inhibitors, PBN and allopurinol, blocked loss of auditory threshold
      sensitivity produced by carbon monoxide. These data suggest that free radical
      generation may play a significant role in the impairment of high-frequency
      auditory sensitivity resulting from carbon monoxide.

PMID- 9007034
TI  - Early life stage toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish
      (Danio rerio).
AB  - Toxicity and histopathology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in
      zebrafish (Danio rerio) early life stages was characterized from 12 to 240 hr
      postfertilization (hpf) following water-borne exposure of newly fertilized eggs.
      TCDD did not increase egg mortality (0-48 hpf), nor did it affect time to
      hatching (48-96 hpf). Egg doses of 1.5 ng [3H]TCDD/g or greater elicited toxic
      responses in zebrafish larvae. Pericardial edema and craniofacial malformations
      were first observed at 72 hpf, followed by the onset of yolk sac edema (96 hpf)
      and mortality (132 hpf). At 240 hpf the ED50s for pericardial edema, yolk sac
      edema, and craniofacial malformations were 2.2, 2.1, and 1.9 ng [3H]TCDD/g egg,
      respectively. The LD50, determined at 240 hpf, was 2.5 ng [3H]TCDD/g egg. Severe
      hemodynamic changes, observed as slowed blood flow in vascular beds of the trunk,
      head, and gills and slowed heart rate, occurred in TCDD-treated zebrafish prior
      to or coincident with the onset of gross signs of toxicity. Histological
      examination of TCDD-treated zebrafish revealed a variety of epithelial tissue
      lesions including arrested gill development and ballooning degeneration and/or
      necrosis of the renal tubules, hepatocytes, pancreas, and all major brain
      regions. Mesenchymal tissue lesions included subcutaneous edema in the head,
      trunk, and yolk sac, edema of the pericardium and skeletal muscle, and
      underdevelopment of the swim bladder. This demonstration of zebrafish
      responsiveness to TCDD early life stage toxicity coupled with the considerable
      information on developmental biology and genetics of zebrafish provides a
      foundation for future investigations into the mechanism of TCDD developmental
      toxicity.

PMID- 9007035
TI  - Coexpression of Ah receptor and CYP1A1 in hepatocytes of C57BL/6J and DBA/2J
      mice.
AB  - The distribution of the hepatic aryl hydrocarbon receptor (AhR) and CYP1A1 was
      investigated in control and 3-methylcholanthrene (3-MC)-treated C57BL/6J (B6) and
      DBA/2J (D2) mice. The AhR was identified as protein bands of 95 and 104 kDa in
      cytosol of B6 and D2 mice, respectively, while a protein of 93 kDa was detected
      in nuclear extracts from both murine strains. CYP1A1 was recognized as a protein
      of 56 kDa in microsomes from B6 and D2 mice. Lower amounts of immunodetectable
      AhR and CYP1A1 were observed in D2 mice, compared to B6 mice. Immunohistochemical
      studies were used to colocalize the AhR and CYP1A1 in adjacent liver sections.
      Staining for the AhR was localized most prominently in the cytoplasm of
      centrilobular hepatocytes and was minimal in the nuclei. Periportal hepatocytes
      were also reactive for the AhR, but the staining was usually localized in the
      nuclei. Other hepatocytes contained moderate amounts of cytoplasmic staining,
      whereas nuclear staining was present at low levels. Immunodetectable CYP1A1 also
      predominated in centrilobular hepatocytes and was negligible in periportal
      hepatocytes. The staining was exclusively cytoplasmic and was not seen in the
      nuclei of hepatocytes. Observations of adjacent liver sections revealed that the
      AhR and CYP1A1 were coexpressed in individual hepatocytes. A similar regional
      distribution for the AhR and CYP1A1 was manifested in B6 and D2 mice, with the
      exception that staining was more pronounced in the former under both control and
      induced conditions. These results showed heterogeneity in the distribution of the
      AhR and CYP1A1, with comparable levels of both proteins residing in the same
      hepatocytes. They further demonstrated that the AhR is localized in both the
      cytoplasm and nuclei of hepatocytes.

PMID- 9007036
TI  - Effect of Taxol on cytochrome P450 3A and acetaminophen toxicity in cultured rat
      hepatocytes: comparison to dexamethasone.
AB  - The purpose of this study was to determine if Taxol induced CYP3A in primary
      cultures of rat hepatocytes and, if so, whether induction of CYP3A would increase
      acetaminophen toxicity. Taxol caused a concentration-dependent increase in the
      amount of immunoreactive CYP3A and in the steady-state levels of CYP3A1/DEX but
      not CYP3A2 mRNA. Similar concentration-dependent increases in toxicity as
      measured by a decrease in protein synthesis were observed after exposure of cells
      to acetaminophen for 7 hr whether cells were pretreated with Taxol or
      dexamethasone. Increased release of lactate dehydrogenase occured after 24 hr
      exposure to acetaminophen, with no further decreases in protein synthesis than
      those observed at 7 hr. Increases in acetaminophen toxicity correlated with
      increased covalent binding of acetaminophen to cellular proteins.
      Triacetyloleandomycin, a selective inhibitor of CYP3A, completely protected the
      cells against acetaminophen toxicity in both Taxol- and dexamethasone-pretreated
      cells and prevented the increase in covalent binding of acetaminophen to cellular
      proteins. These results demonstrate that Taxol, like dexamethasone, induces CYP3A
      and that increases in this P450 are responsible for increased acetaminophen
      toxicity.

PMID- 9007037
TI  - Toxicity of allyl alcohol in primary cultures of freshly isolated and
      cryopreserved hepatocytes maintained on hydrated collagen gels.
AB  - The toxicity of allyl alcohol was compared in freshly isolated and cryopreserved
      hepatocytes that were either placed in suspension or maintained on hydrated
      collagen gels in a sandwich configuration. The purpose of this study was to
      evaluate whether the two types of cells displayed the same sensitivity to allyl
      alcohol when maintained in vitro over relatively prolonged periods of time. The
      important differentiated functions of urea synthesis, secretion of albumin, and
      metabolism of ethoxycoumarin, a model drug substrate, were used as end points of
      toxicity. Cryopreserved hepatocytes incubated in physiological buffer shortly
      after removal from liquid nitrogen were more sensitive to allyl alcohol than
      freshly isolated hepatocytes. In contrast, cryopreserved and freshly isolated
      hepatocytes maintained on hydrated collagen gels responded identically to allyl
      alcohol. Thus, the increased sensitivity of cryopreserved hepatocytes in
      suspension to allyl alcohol is a transient phenomenon that disappears after the
      cells have been allowed to recover on hydrated collagen gels. Dissipation of the
      mitochondrial membrane potential by allyl alcohol, as indexed by rhodamine 123
      fluorescence, was also the same in freshly isolated and cryopreserved hepatocytes
      maintained on hydrated collagen matrices. This loss of mitochondrial membrane
      potential caused by allyl alcohol preceded inhibition of albumin and urea
      biosynthesis. Collectively, the results indicate that cryopreserved cells
      maintained on hydrated collagen gels provide a useful system to define the
      actions of certain hepatotoxic agents over relatively prolonged periods of time
      in vitro.

PMID- 9007038
TI  - CS2-mediated cross-linking of erythrocyte spectrin and neurofilament protein:
      dose response and temporal relationship to the formation of axonal swellings.
AB  - Using model proteins, a mechanism for CS2-mediated covalent cross-linking of
      proteins has been demonstrated previously. The biologic importance of CS2
      promoted protein cross-linking is apparent as a possible dosimeter of CS2
      exposure and as a potential mechanism to account for the identical neuropathies
      produced by 2,5-hexanedione and CS2. The present investigation examines the
      utility of erythrocyte spectrin cross-linking as a biomarker of effect for
      inhalation exposure to CS2 and examines the ability of CS2 to cross-link
      neurofilament proteins, a potential neurotoxic target. Rats were exposed to CS2
      via inhalation at control, 50-, 500-, and 800-ppm levels for 2, 4, 8, and 13
      weeks and spectrin dimer formation was quantified using denaturing gel
      electrophoresis and densitometry. Neurofilament preparations were also obtained
      from spinal cords and examined for cross-linking using Western blotting methods.
      The results obtained for protein cross-linking were compared to morphologic
      changes in the cervical and lumbar spinal cord using light and electron
      microscopy. The spectrin dimer exhibited a cumulative dose response and was
      detectable at both the 50-ppm level employed that did not produce axonal
      swellings and prior to the development of axonal swellings for the 500- and 800
      ppm levels used. Neurofilament protein cross-linking involved all three subunits
      and the temporal relationship of cross-linking was consistent with a contributing
      role in the development of axonal swellings. These results establish the
      sensitivity of spectrin cross-linking for evaluating inhalation exposures and
      extend the similarities observed for 2,5-hexanedione and CS2 in both clinical
      settings and in vitro models to their effects exerted on neurofilaments in the
      axon.

PMID- 9007039
TI  - Lead/cytokine-mediated oxidative DNA damage in cultured mouse hepatocytes.
AB  - Hepatocytes exposed to the cytokines tumor necrosis factor alpha (TNFalpha) and
      interferon gamma (IFNgamma), in combination with a nontoxic dose of lead (Pb),
      exhibited significantly greater cytotoxicity compared to cytokine-treated
      hepatocytes after 24 hr treatment. Concentrations of Pb which interact with the
      cytokines to cause cytotoxicity stimulated hepatocytes cultured at this high cell
      density (63,830 cells/cm2) to undergo active DNA synthesis. DNA synthesis was
      also observed in hepatocytes plated at a low cell densities (21,276 cells/cm2)
      and these cells were sensitive to the toxic effects of the cytokines in the
      absence of Pb. Under conditions of active DNA synthesis, induced by either Pb or
      cell density, cytokine-induced toxicity appeared to be the result of extensive
      DNA fragmentation. Both DNA fragmentation and cytotoxicity were inhibited by
      treatment with an antioxidant mixture. Pb potentiated cytokine-induced oxidative
      stress within hepatocytes as indicated by decreased intracellular glutathione
      (GSH) and increased efflux of oxidized glutathione (GSSG) prior to cytotoxicity.
      The combination of cytokines and Pb also caused a significant decline in
      intracellular ATP concentrations prior to the onset of cytotoxicity. ATP
      concentrations were not altered by treatment with Pb or cytokines alone. Pb
      treatment did not alter total protein synthesis within hepatocytes. These results
      indicate that the cytotoxic interaction between Pb and the cytokines TNFalpha and
      IFNgamma may be mediated by oxidative DNA damage resulting from cytokine-induced
      oxidative stress and stimulation of mitogenic signals.

PMID- 9007040
TI  - Inhibition of bile-salt-induced hepatocyte apoptosis by the antioxidant lazaroid
      U83836E.
AB  - Intracellular retention of toxic bile salts contributes to hepatocellular injury
      during cholestasis. We have recently demonstrated that toxic bile salts directly
      induce apoptosis in hepatocytes. As oxidative stress has been implicated in many
      models of apoptosis, our aim was to determine if oxidative injury is a critical
      event during bile-salt-induced hepatocyte apoptosis. Cultured rat hepatocytes
      incubated with 50 microM glycochenodeoxycholate (GCDC) exhibited the
      characteristic morphological features of apoptosis such as nuclear fragmentation
      and cellular fragmentation into organelle-containing membrane-bound apoptotic
      bodies. After a 3-hr incubation, apoptosis was observed in 60 +/- 8% of cells
      compared to <1% in controls. GCDC-induced apoptosis was associated with lipid
      peroxidation as demonstrated by an increase in 8-isoprostane release. The
      antioxidant lazaroid U83836E inhibited 8-isoprostane generation during GCDC
      induced hepatocye apoptosis. In addition, U83836E also reduced GCDC-mediated
      apoptosis by 70% as assessed using both stringent morpholgic (nuclear
      fragmentation) and biochemical (determination of DNA strand breaks) criteria. In
      summary, during treatment of hepatocytes with GCDC, (1) apoptosis is associated
      with lipid peroxidation, and (2) the antioxidant lazaroid U83836E inhibits both
      lipid peroxidation and apoptosis. In conclusion, these data suggest that
      oxidative stress contributes to bile-salt-induced apoptosis. We speculate that
      antioxidants may be useful in ameliorating liver injury during chronic
      cholestasis.

PMID- 9007041
TI  - In vitro metabolism of 7,12-dimethylbenz[a]anthracene by rainbow trout liver
      microsomes and trout P450 isoforms.
AB  - Liver microsomes from juvenile trout metabolized DMBA to unknown highly polar
      metabolites (X) and to DMBA-t-5,6-diol, DMBA-t-8,9-diol, 7-OHM-12-MBA, 7M-12
      OHMBA, 2-OH-DMBA, 4-OH-DMBA, and trace amounts of DMBA-t-3,4-diol. Treatment of
      trout with beta-naphthoflavone (BNF) and isosafrole (ISF) increased the formation
      of these products except for the hydroxymethyl derivatives of DMBA. The
      production of DMBA-t-3,4-diol, 2-OH-DMBA, and 4-OH-DMBA was much greater in BNF
      induced liver microsomes than that in ISF-induced liver microsomes. In contrast,
      the yield of DMBA-t-8,9-diol and 7-OHM-12-MBA was greater in ISF-induced
      microsomes than that in BNF-induced microsomes. Trout CYP1A1 (P450 LM4b) purified
      from BNF-treated trout catalyzed the formation of the same metabolites generated
      by BNF-induced microsomes in the presence of added human microsomal EH. The
      constitutive forms of P450 isolated from untreated trout such as P450s LMC3,
      LMC4, and LMC5, CYP2M1 (P450 LMC1), and CYP2K1 (P450 LMC2) did not produce any of
      the DMBA metabolites (except for DMBA-t-8,9-diol by CYP2K1) generated by the
      trout microsomes. Generation of DMBA-DNA and DMBA-protein adducts in vitro was
      enhanced by treatment of trout with BNF and by ISF to a lesser extent. Formation
      of adducts and DMBA diols by BNF-induced liver microsomes and by trout CYP1A1 was
      completely blocked by the CYP1A inhibitor ellipticine (100 microM). These results
      suggest that the BNF-inducible trout P450 (CYP1A), not the constitutive P450s, is
      the major catalyst for the biotransformation of DMBA to metabolites that bind to
      macromolecules.

PMID- 9007043
TI  - Hepatic microsomal enzyme induction, beta-oxidation, and cell proliferation
      following administration of clofibrate, gemfibrozil, or bezafibrate in the CD
      rat.
AB  - Male and female CD rats were administered one of two dose levels of clofibrate,
      gemfibrozil, or bezafibrate daily by oral gavage for a period of 14 days in order
      to establish an empirical data base using the Charles River CD rat with a single
      class of drugs against which the potency of novel proprietary compounds could be
      compared. Subsequent gross examination of the liver indicated significant and
      dose-related increases in relative and absolute liver weights in males following
      clofibrate and gemfibrozil. In females, absolute and relative liver weights were
      significantly elevated to a similar degree with either dose of gemfibrozil, and
      absolute liver weights were higher in clofibrate-dosed animals. Bezafibrate had
      no effect on female liver weights. Clofibrate and gemfibrozil increased hepatic
      palmitoyl CoA beta-oxidation in both sexes; however, clofibrate had the greater
      effect in males and gemfibrozil had the least effect in females. Bezafibrate
      treatment resulted in a very pronounced elevation of palmitoyl CoA beta-oxidation
      in the males but had no similar effect in the females. Concurrent ELISA analysis
      for cytochrome CYP4A revealed very good correspondence between beta-oxidation and
      cytochrome induction for each of the three compounds in males, but other
      cytochromes were not greatly affected, except CYP1A1 which was elevated in
      bezafibrate-dosed females. For males, further analysis for markers of cellular
      proliferation, namely cyclin-dependent kinases (CDK) and proliferating cell
      nuclear antigen (PCNA), indicated dose-related increases for both with
      clofibrate, increases at the high dose for gemfibrozil, and, for PCNA, a dose
      related increase for bezafibrate. In females, both markers for cell proliferation
      showed either slight or no increases following any of the three drug treatments.
      These results demonstrate clear sex-dependent differences in terms of relative
      potency in the hepatic response of the Sprague-Dawley-derived rat to these
      peroxisome proliferators. Bezafibrate is most potent and gemfibrozil is least
      potent in stimulating peroxisome-associated beta-oxidation and cytochrome P450 4A
      induction in the males. Even though gemfibrozil significantly increased liver
      weights, beta-oxidation and cytochrome P450 4A in the females increased only
      after clofibrate treatment, although to a lesser degree than in the males
      administered the same dose. Similar sex-related differences were observed for
      cell proliferation. In conclusion, sex-related differences were noted in the
      potency to stimulate acyl Co-A oxidation, its association with hepatomegaly, and
      the stimulation of cell proliferation, but CYP4A induction always accompanied any
      substantial drug-dependent increases in beta-oxidation.

PMID- 9007042
TI  - Mechanism of thiazopyr-induced effects on thyroid hormone homeostasis in male
      Sprague-Dawley rats.
AB  - Chronic administration of thiazopyr in the diet at dose levels of 1000 and 3000
      ppm, but not 100 ppm, has demonstrated an increase in thyroid follicular cell
      tumors in male Sprague-Dawley rats. In the studies reported here we have
      evaluated the mechanism of thiazopyr-induced thyroid tumors by studying the
      effect of thiazopyr on a number of endpoints that indicate hypothalamic-pituitary
      thyroid homeostasis. At a dose level of 3000 ppm, thiazopyr caused a marked
      depression in circulating levels of T4 as soon as 7 days after commencement of
      treatment. Concurrent with this decrease in T4 was an increase in TSH levels, an
      increase in thyroid and liver weights, a three- to sixfold increase in hepatic T4
      uridine diphosphate glucuronosyl transferase (UDPGT) activity, and increases in
      thyroid follicular cell hypertrophy and hyperplasia. Dose-related changes
      associated with thiazopyr treatment were significant increases in liver weight,
      thyroid weight, and hepatic T4-UDPGT activity at high doses. Increased levels of
      serum TSH, T3, and rT3, decreased levels of T4, and an increased incidence of
      thyroid follicular cell hypertrophy and hyperplasia were observed 56 days after
      the initiation of 3000 ppm thiazopyr. All the changes, except thyroid weight,
      were partially or completely reversible upon removal of thiazopyr from the diet.
      Increased thyroid T4 elimination, primarily via increased hepatic conjugation by
      T4-UDPGT, resulting in decreased serum T4, appeared to be responsible for the
      increased TSH levels. The sustained increase in TSH by thiazopyr appears
      responsible for the stimulation of the thyroid follicular cells resulting in
      follicular cell hypertrophy, hyperplasia, and ultimately neoplasia. In summary,
      evidence is presented for a hormonally mediated, threshold-dependent process for
      the development of thyroid follicular cell tumors from high-dose thiazopyr
      administration in male rats. This mechanism is not considered to be relevant to
      humans, since the thyroid of humans is much less sensitive to this pathogenic
      phenomenon than rodents.

PMID- 9007044
TI  - Human ingestion of chromium (VI) in drinking water: pharmacokinetics following
      repeated exposure.
AB  - Regulatory agencies have established safe drinking water concentrations for
      hexavalent chromium [Cr(VI)] based in part on the presumed capability of human
      gastric juices to rapidly reduce Cr(VI) to nontoxic trivalent chromium [Cr(III)]
      prior to systemic absorption. This study examines dose-related pharmacokinetics
      in humans following repeated oral exposure to Cr(VI) in drinking water. In
      particular, we sought to examine whether plausible drinking water exposures to
      Cr(VI) caused a sustained increase in red blood cell chromium levels, a specific
      marker for systemic uptake of Cr(VI). Adult male volunteers ingested a liter (in
      three volumes of 333 ml, at approximate 6-hr intervals) of deionized water
      containing Cr(VI) concentrations ranging from 0.1 to 10.0 mg/liter. Samples of
      urine, plasma, and red blood cells were collected and analyzed for chromium. A
      dose-related increase in urinary chromium excretion was observed in all
      volunteers. Red blood cell and plasma chromium concentrations became elevated in
      certain individuals at the highest doses. The RBC chromium profiles suggest that
      the ingested Cr(VI) was reduced to Cr(III) before entering the bloodstream, since
      the chromium concentration in the RBCs dropped rapidly postexposure. These
      findings suggest that the human gastrointestinal tract has the capacity to reduce
      ingested Cr(VI) following ingestion of up to 1 liter of water containing 10.0
      mg/liter of Cr(VI), which is consistent with USEPA's position that the Cr(VI)
      drinking water standard of 0.10 mg Cr(VI)/liter is below the reductive capacity
      of the stomach.

PMID- 9007045
TI  - Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners
      identified in human serum.
AB  - Several hydroxylated polychlorinated biphenyls (PCBs) identified in human serum
      have been synthesized and these include 2,2',3,4',5,5'-hexachloro-4-biphenylol;
      2,3,3',4',5-pentachloro-4-biphenylol; 2',3,3',4',5-pentachloro-4-biphenylol;
      2,2',3,3',4',5-hexachloro-4-biphenylol; 2,2',3,3',4',5,5'-heptachloro-4
      biphenylol; 2,2',3,4',5,5',6-heptachloro-4-biphenylol; and 2,2',3',4,4',5,5'
      heptachloro-3-biphenylol. The hydroxy-PCBs exhibited minimal binding to the rat
      uterine cytosolic estrogen receptor (ER) and did not induce proliferation of
      estrogen-responsive MCF-7 human breast cancer cells at concentrations ranging
      from 10(-5) to 10(-8) M. The estrogenic activity of these compounds was further
      investigated utilizing two estrogen-responsive in vitro bioassays, namely, (i)
      HeLa cells stably transfected with a Gal4:human ER chimera and a 17-mer-regulated
      luciferase reporter gene, and (ii) MCF-7 cells transiently transfected with a
      full-length human ER expression plasmid and a plasmid containing an estrogen
      responsive vitellogenin A2 promoter linked to a chloramphenicol acetyl
      transferase (CAT) reporter gene. None of the hydroxy-PCBs significantly induced
      luciferase activity in the stably transfected HeLa cells or CAT activity in MCF-7
      cells at concentrations as high as 10(-5) M. The antiestrogenic effects of the
      hydroxy-PCBs were also investigated using the same bioassays in which the cells
      were cotreated with 17beta-estradiol plus the hydroxy-PCBs. All of the hydroxy
      PCB congeners inhibited one or more estrogenic response, and one congener,
      2,2',3,4',5,5',6-heptachloro-4-biphenylol, inhibited 17beta-estradiol-induced
      cell proliferation and CAT activity in MCF-7 cells and luciferase activity in
      HeLa cells.

PMID- 9007047
TI  - Progesterone pretreatment enhances cellular sensitivity to cadmium despite a
      marked activation of the metallothionein gene.
AB  - Previously, we found that in vivo pretreatment with progesterone markedly
      increased cadmium lethality in rats, apparently by enhancing cadmium-induced
      hepatonecrosis. Therefore, the present study was designed to investigate this
      phenomenon at the molecular level in an in vitro system. TRL-1215 rat liver cells
      were exposed to various concentrations of progesterone (0, 1, 10, and 100 microM)
      for 24 hr and subsequently exposed to cadmium (0, 1, 5, 10, and 50 microM; as
      CdCl2) for an additional 24 hr. Although the levels of progesterone used were
      essentially nontoxic, progesterone pretreatment resulted in a concentration
      dependent increase in sensitivity to cadmium as assessed by loss of mitochondrial
      enzyme activity (tetrazolium-based dye assay) and loss of cytosolic enzyme
      activity (glutamic oxaloacetic transaminase). The effects of progesterone
      treatment on intracellular levels of metallothionein (MT), an inducible metal
      binding protein generally associated with cadmium tolerance, were also measured.
      Progesterone (100 microM) alone increased MT levels 2.4-fold, while cadmium (10
      microM) alone resulted in a 7-fold increase over control. Progesterone
      pretreatment followed by cadmium exposure caused a marked, 16-fold induction in
      MT synthesis, a level of activity that has been associated with acquired
      tolerance to cadmium. In addition, progesterone pretreatment clearly induced
      transcription of the MT gene as evidenced by enhanced cadmium-induced
      accumulation of cellular MT mRNA. Progesterone pretreatment had no effect on the
      level of glutathione, a cellular thiol thought to be important in detoxication of
      cadmium prior to MT gene activation and MT protein accumulation, or on cellular
      accumulation of cadmium during the initial 3 hr of exposure to the metal. The
      proportion of total cellular cadmium bound to MT in cells pretreated with
      progesterone was greater than that in the cells treated with cadmium alone,
      indicating an enhanced sequestration of the metal by MT after pretreatment. These
      results indicate that progesterone, at nontoxic levels, markedly exacerbates
      cadmium toxicity at the cellular level in liver cells. This is in accord with the
      observed progesterone-induced enhancement of the hepatotoxic effects of cadmium
      in vivo. The observed facilitation of cytotoxicity is not based in altered
      toxicokinetics of cadmium and occurs despite a pronounced activation of the MT
      gene resulting in an enhanced sequestration of cadmium by MT. The mechanism by
      which progesterone enhances cadmium toxicity deserves further study.

PMID- 9007046
TI  - Induction and inhibition of mouse cytochrome P-450 2B enzymes by musk xylene.
AB  - Musk xylene (MX) (1,3,5-trinitro-2-t-butylxylene) is a nitromusk perfume
      ingredient that although uniformly negative in a battery of genotoxicity tests,
      produces a high incidence of liver tumors in mice. The purpose of this work was
      to characterize the profile and dose-response relationship of microsomal enzyme
      induction following exposure to MX. MX was dosed by gavage to male B6C3F1 mice
      for 7 days at 0, 1, 5, 10, 20, 50, 100, and 200 mg/kg after which microsomes were
      prepared. At 200 mg/kg, MX increased liver weight by about 65% and increased
      microsomal cytochrome P-450 content 2-fold over control. MX increased microsomal
      activity for O-dealkylation of 7-ethoxy and 7-methoxyresorufin 4- and 2-fold,
      respectively, and increased the N-demethylation of erythromycin approximately 2
      fold. These results were generally consistent with increased CYP1A1, 1A2, and 3A
      protein levels determined by Western blotting. In contrast, whereas no increase
      in O-dealkylation of 7-pentoxyresorufin (PROD) was observed, MX treatment
      increased CYP2B protein levels about 25-fold over control at 200 mg/kg.
      Furthermore, a single dosage of MX (200 mg/kg) increased Cyp2b-10 mRNA to a
      maximal level and with a time course similar to phenobarbital (PB). To study
      inhibition of CYP2B enzymes in vivo, mice were treated with PB (0.05% in drinking
      water for 5 days), then given a single dosage of corn oil or MX (200 mg/kg) at 2
      or 18 hr before necropsy. PB treatment increased PROD activity 25-fold, and at 2
      hr after MX treatment (associated with peak plasma levels of MX), there was no
      change in the PB-induced PROD activity. However, at 18 hr, MX treatment decreased
      PROD activity by 90%. Despite the in vivo inhibition, in vitro studies indicated
      that MX did not cause mechanism-based inactivation of CYP2B enzymes. The
      potential for nitroreduction of MX (catalyzed by anaerobic intestinal bacteria)
      to contribute to the inhibition of CYP2B enzyme activity was evaluated in a
      separate group of PB-induced mice that were dosed orally with a regimen of broad
      spectrum antibiotics (neomycin, tetracyline, and bacitracin) to reduce gut flora
      prior to administration of MX. In these animals, MX (200 mg/kg) did not inhibit
      PB-induced PROD activity. In summary, MX treatment produced general hepatic
      changes consistent with induction of CYP2B enzymes in mice and caused a large
      increase in CYP2B protein and mRNA levels. These data indicate that MX is a PB
      like inducer of cytochrome P-450 enzymes and may cause liver tumors in a manner
      analogous to PB. However, no increase in CYP2B enzyme activity was observed,
      suggesting that MX or metabolites of MX also inhibit this enzyme. When the
      intestinal flora was eliminated by antibiotic treatment, MX no longer inhibited
      the CYP2B enzyme, indicating that anaerobic bacteria are capable of metabolizing
      MX, and suggesting that amine metabolites formed by nitroreduction are involved
      in the inhibition of mouse CYP2B enzymes.

PMID- 9007048
TI  - R(-)-deprenyl potentiates dopamine-induced cytotoxicity toward catecholaminergic
      neuroblastoma SH-SY5Y cells.
AB  - Autoxidation of dopamine or L-DOPA (3,4-dihydroxyphenylalanine) generates
      reactive oxygen species (ROS), i.e., hydrogen peroxide, superoxide, and hydroxyl
      radical, which are potentially cytotoxic. Increased formation of ROS has been
      proposed to be involved in the pathogenesis of many human diseases, including
      Parkinson's disease. Several reports suggest that R(-)-deprenyl (an MAO-B
      inhibitor and anti-Parkinsonian drug) may directly or indirectly exert
      antioxidant effects and thus protect neurons. We have assessed the toxic effects
      of dopamine and L-DOPA toward catecholaminergic neuroblastoma SH-SY5Y cells and
      whether R(-)-deprenyl and several structurally related compounds possess
      antioxidant effects in this system. The results show that both dopamine and L
      DOPA are quite cytotoxic toward SH-SY5Y cells. R(-)-deprenyl rather than reducing
      this dopamine-induced toxicity actually enhances it. Structural analogues of R(-)
      deprenyl, such as 4-methyldeprenyl, (-)-methylamphetamine, and clorgyline,
      exhibited similar effects. Some different MAO-B inhibitors, namely, the aliphatic
      N-methylpropargylamines, e.g., (+/-)-M-2-PP [N-(2-pentyl)-N-methylpropargylamine]
      and N-[2-hexyl]-N-methylpropargylamine, which can also protect and rescue neurons
      in several in vivo and in vitro models, did not exacerbate the cytotoxicity of
      dopamine. Neither R(-)-deprenyl nor (+/-)-M-2-PP affected the L-DOPA-induced
      cytotoxicity toward SH-SY5Y cells.

PMID- 9007049
TI  - Vinclozolin and p,p'-DDE alter androgen-dependent gene expression: in vivo
      confirmation of an androgen receptor-mediated mechanism.
AB  - Vinclozolin and p,p'-DDE induce antiandrogenic developmental effects in vivo and
      are potent inhibitors of androgen receptor (AR) binding and AR-dependent gene
      expression in vitro. To determine whether this molecular mechanism is operative
      in vivo, the effects of these compounds on two androgen-regulated prostatic mRNAs
      were studied. Rats were sham operated or castrated and immediately implanted with
      one or two empty 2.5-cm silastic capsules or with one (1x) or two (2x) 2.5-cm
      capsules containing testosterone (T). T-implanted rats were treated by gavage for
      4 days with vehicle (corn oil), vinclozolin (200 mg/kg/day), p,p'-DDE (200
      mg/kg/day), or the antiandrogen flutamide (100 mg/kg/day) as a positive control.
      Vinclozolin, p,p'-DDE, and flutamide all induced a reciprocal decline in seminal
      vesicle (p < 0.01) and prostate (p < 0.01) weight as well as a reduction in
      immunohistochemical staining of AR in epididymal nuclei compared to vehicle
      treated T-implanted controls. Specific AR antagonism was assessed by determining
      the ability of these chemicals to induce a testosterone-repressed prostatic
      message (i.e., TRPM-2) and/or repress a testosterone-induced prostatic message
      (i.e., prostatein subunit C3). Densitometry scans of Northern blots indicated
      that vinclozolin, p,p'-DDE, and flutamide each induced TRPM-2 mRNA and repressed
      C3 mRNA compared to vehicle-treated T-implanted controls. These antiandrogenic
      effects were competitively reduced in castrate rats implanted with two 2.5-cm T
      capsules (2x), where serum T levels were elevated more than twofold above
      physiological levels. Taken together, these data indicate that vinclozolin and
      p,p'-DDE act as antiandrogens in vivo by altering the expression of androgen
      dependent genes.

PMID- 9007050
TI  - Late dimethyl sulfoxide administration provides a protective action against
      chemically induced injury in both the liver and the kidney.
AB  - Dimethyl sulfoxide (DMSO) can protect the liver from injury produced by a variety
      of hepatotoxicants when administered prior to or concomitant with the toxicants.
      This protective action has previously been attributed to DMSO-induced inhibition
      of bioactivation of the compounds to toxic intermediates. In these studies, the
      ability of DMSO to provide protection when administered 10 hr after a toxicant
      was evaluated in several animal models of xenobiotic-induced liver and kidney
      injury. In the guinea pig model of halothane-associated hepatotoxicity, male
      outbred Hartley guinea pigs received 2 ml/kg DMSO 10 hr after an inhalation
      exposure to 1.0% halothane, 40% O2 for 4 hr. DMSO decreased the extent of liver
      necrosis as indicated by a threefold decrease in plasma alanine aminotransferase
      activity 48 hr after exposure and a reduction in the incidence and extent of zone
      3 necrosis. These results do not appear to be due to alterations in halothane
      biotransformation since DMSO administered at 10 hr after halothane had no affect
      on plasma concentrations of the halothane metabolite tritluoroacetic acid or
      covalent binding by reactive halothane biotransformation intermediates to hepatic
      protein. In addition, administration of the structurally analogous
      biotransformation inhibitor diallyl sulfide at 10 hr after halothane also had no
      affect on biotransformation or covalent binding but provided no protection from
      liver injury. Hepatic glutathione concentrations in the guinea pigs 24 hr after
      halothane exposure were also unaffected by late treatment with DMSO. Further
      studies in male Sprague-Dawley rats demonstrated the ability of DMSO to decrease
      the hepatic injury resulting from oral administration of 1.0 ml/kg chloroform or
      0.5 ml/kg bromobenzene when administered 10 hr after either toxicant. The
      chloroform-treated rats also developed renal tubular necrosis with large
      increases in plasma creatinine and urea nitrogen, which were completely
      ameliorated by DMSO. Elucidating the mechanism(s) of this protective action of
      late DMSO administration should provide insight into the cascade of events that
      lead to liver and kidney injury from toxicants and, hopefully, therapeutic
      modalities for individuals suffering from acute, progressing, xenobiotic-induced
      hepatitis.

PMID- 9007052
TI  - A proposed mechanism of mRNA synthesis and capping by vesicular stomatitis virus.

PMID- 9007051
TI  - Sphingolipids--the enigmatic lipid class: biochemistry, physiology, and
      pathophysiology.
AB  - The "sphingosin" backbone of sphingolipids was so named by J. L. W. Thudichum in
      1884 for its enigmatic ("Sphinx-like") properties. Although still an elusive
      class of lipids, research on the involvement of sphingolipids in the signal
      transduction pathways that mediate cell growth, differentiation, multiple cell
      functions, and cell death has been rapidly expanding our understanding of these
      compounds. In addition to the newly discovered role of ceramide as an
      intracellular second messenger for tumor necrosis factor-alpha, IL-1beta, and
      other cytokines, sphingosine, sphingosine-1-phosphate, and other sphingolipid
      metabolites have recently been demonstrated to modulate cellular calcium
      homeostasis and cell proliferation. Perturbation of sphingolipid metabolism using
      synthetic and naturally occurring inhibitors of key enzymes of the biosynthetic
      pathways is aiding the characterization of these processes; for examples,
      inhibition of cerebroside synthase has indicated a role for ceramide in cellular
      stress responses including heat shock, and inhibition of ceramide synthase (by
      fumonisins) has revealed the role of disruption of sphingolipid metabolism in
      several animal diseases. Fumonisins are currently the focus of a FDA long-term
      tumor study. This review summarizes recent research on (i) the role of
      sphingolipids as important components of the diet, (ii) the role of sphingoid
      base metabolites and the ceramide cycle in expression of genes regulating cell
      growth, differentiation, and apoptosis, (iii) the use of cerebroside synthase
      inhibitors as tools for understanding the role of sphingolipids as mediators of
      cell cycle progression, renal disease, and stress responses, and (iv) the
      involvement of disrupted sphingolipid metabolism in animal disease and cellular
      deregulation associated with exposure to inhibitors of ceramide synthase and
      serine palmitoyltransferase, key enzymes in de novo sphingolipid biosynthesis.
      These findings illustrate how an understanding of the function of sphingolipids
      can help solve questions in toxicology and this is undoubtedly only the beginning
      of this story.

PMID- 9007053
TI  - Dual NF1-requiring effect of human neurotropic JC virus composite pentanucleotide
      repeat elements on early and late viral gene expression.
AB  - Human polyoma JC virus (JCV) is a largely brain cell-specific virus that is
      associated with AIDS. The neurotropism involves the various transcription factors
      interacting with their cognate sequences in the JCV early (JCVE) and late (JCVL)
      promoters-enhancer, but the mechanism is unclear. The JCV tandem AGGGA
      pentanucleotide double repeat element (Pnt2) and the abutting NF1 site form a
      composite Pnt2 (cPnt2). Here, we studied the roles of both sites of cPnt2 in the
      expression of JCVE and JCVL. JCVE activity was progressively increased in U-87 MG
      human glioblastoma cells following the site-specific mutation of Pnt2 in one and
      both 98-bp repeats. In contrast, the activity for JCVL was progressively reduced
      by mutating single and double Pnt2s. However, JCVE activity was unaffected by
      mutating both Pnt2s when both NF1 sites of cPnt2 were mutated. The activity of
      JCVL was also unaffected by double Pnt2 mutations after the NF1 sites were
      mutated. Differentiating P19 glial cells showed similar results. Next, Pnt2
      interacting proteins were examined by two in vitro assays with a Pnt2
      oligonucleotide. Mobility shift assays showed one Pnt2-protein complex for U-87
      MG cell extracts and two for P19 glial cell extracts. However, similar results
      were obtained for glial, muscle, and undifferentiated P19 cells. In UV cross
      linking assays, two Pnt2-binding proteins (Pnt2BPs) were detected. The results
      suggested that the effects on JCVE and JCVL expression of Pnt2BP and NF1 via
      cPnt2 are dual and require a glial cell-specific NF1 function.

PMID- 9007054
TI  - Cations in human rhinoviruses.
AB  - All known crystal structures of rhinoviruses have some uninterpreted electron
      density on their fivefold axes at a distance of about 152 +/- 3 A from the viral
      center. This density had been assumed to be a Ca2+ ion, based on its shape,
      height, and the presence of Ca2+ ions in the crystallization solutions.
      Difference electron density maps between EGTA-soaked crystals of human rhinovirus
      14 (HRV14), as well as HRV16, and their corresponding native structures show that
      this density is an EGTA-chelatable ion. Analysis of the coordination geometry
      indicates that the ions in HRV3, HRV14, and HRV1A could be Ca2+ and the ion in
      HRV16 might be Zn2+. These cations may play a role in regulation of rhinovirus
      stability, although the loss of the ion itself does not seem sufficient to lead
      to viral disassembly.

PMID- 9007055
TI  - Plasmas from lymphocyte- and macrophage-tropic SIVmac-infected macaques have
      antibodies with a broader spectrum of virus neutralization activity in macrophage
      versus lymphocyte cultures.
AB  - We examined plasma from macaques infected with three different phenotypes of
      SIVmac for their ability to neutralize the infectivity of homologous and
      heterologous virus in lymphocyte (CEMx174 cells or normal rhesus macaque
      peripheral blood lymphocytes) or normal rhesus macaque macrophage (Mphi)
      cultures. Similar to previous findings, we observed that some plasmas failed to
      neutralize or poorly neutralized the infectivity of SIVmac239 and SIVmac251(<1:20
      plasma dilution) in lymphocyte cultures. In contrast, when primary rhesus Mphi
      cultures were used as the indicator cells, the same plasmas neutralized both
      viruses at high dilutions (1:200 to 1:20,000). Neutralization of virus
      infectivity by the various plasmas was confirmed by SIV core antigen capture
      assays. We excluded the possibility that this differential neutralization in Mphi
      was related to the differences in the ability of the virus strain to replicate in
      these two cell types by demonstrating that the replication efficiency of
      SIVmac251 in CEMx174 cells, PBMC, and Mphi cultures was very similar. The role of
      Fc receptors on the Mphi surface in the clearance of the virus-antibody complexes
      was also excluded since similar neutralizing results were obtained using whole
      plasmas, purified IgG antibodies, and purified Fab fragments derived from the IgG
      fraction of these plasmas. The mechanism of virus neutralization in Mphi does not
      appear to involve blocking of virus entry into the cells since radiolabeled virus
      reacted with anti-SIV antibodies was taken up by rhesus Mphi as efficiently as
      virus reacted with normal antibody. DNA of the neutralized virus was identified
      in the Mphi cultures, but virus replication, as evidenced by accumulation of
      viral protein products, was not detectable so long as the antibodies were present
      in the medium. Removal of the antibodies resulted in a resumption of virus
      replication in the Mphi. These results indicate that virus infectivity can be
      efficiently neutralized by antibodies in Mphi cultures by a mechanism that is
      fundamentally different from that in lymphocyte cultures.

PMID- 9007057
TI  - Identification of HIV-1 determinants for replication in vivo.
AB  - Pathogenic organisms are frequently attenuated after long-term culture in vitro.
      The mechanisms of the attenuation process are not clear, but probably involve
      mutations of functions required for replication and pathogenicity in vivo. To
      identify these functions, a direct comparison must be made between attenuated
      genomes and those that remain pathogenic in vivo. In this study, we used the
      heterochimeric SCID-hu Thy/Liv mouse as an in vivo model to define human
      immunodeficiency virus type 1 (HIV-1) determinants which are uniquely required
      for replication in vivo. The Lai/IIIB isolate and its associated infectious
      molecular clones (e.g., HXB2) were found to infect T cell lines but failed to
      replicate in the SCID-hu Thy/Liv model. When a lab worker was accidentally
      infected by Lai/IIIB, however, HIV-1 was isolated only from infection of primary
      PBMC, and not from infection of T cell lines. We hypothesized that the lab worker
      was exposed to a heterogeneous viral stock which had been attenuated by passage
      in immortalized T cell lines. Either a rare family member from this stock was
      selected for in vivo replication or, alternatively, an attenuated genotype
      dominant in vitro may have reverted to become more infectious in vivo. To address
      this hypothesis, we have used the SCID-hu Thy/Liv model to study the replication
      of HXB2 and of HXB2 recombinant viruses with HIV-1 fragments isolated from the
      infected lab worker. HXB2 showed no or very low levels of replication in the
      Thy/Liv organ. Replacement of its subgenomic fragment encoding the envelope gene
      with a corresponding fragment from the lab worker isolate generated a recombinant
      virus (HXB2/LW) which replicated actively in SCID-hu mice. The NEF mutation in
      the HXB2 genome is still present in HXB2/LW. Thus, the LW sequences encode HIV-1
      determinants which enhance HIV replication in vivo in a NEF-independent
      mechanism. The specific determinants have been mapped to the V1-V3 regions of the
      HIV-1 genome. Six unique mutations in the V3 loop region of HXB2/LW have been
      identified which contribute to the increased replication in vivo.

PMID- 9007058
TI  - Complementation of defective picornavirus internal ribosome entry site (IRES)
      elements by the coexpression of fragments of the IRES.
AB  - Mutant forms of the encephalomyocarditis virus (EMCV) internal ribosome entry
      site (IRES) have been produced and shown to be severely defective in directing
      internal initiation of protein synthesis within cells using the vaccinia/T7 RNA
      polymerase system. Mutants in different regions of the IRES were complemented in
      trans by coexpression of the intact EMCV IRES but not by coexpression of the
      related IRES elements from Theiler's murine encephalomyelitis virus (another
      cardiovirus) or from foot-and-mouth disease virus. Distinct, truncated regions of
      the EMCV IRES, insufficient to direct internal initiation, were also shown to
      complement defective EMCV IRES elements. It was necessary for the complementing
      molecule, whether truncated or full length, to be expressed in the positive sense
      orientation. RT-PCR analysis provided no support for the idea that any
      recombination event was responsible for the complementation. The data suggest
      that multiple activities are performed by distinct functional entities within the
      IRES in the process of internal initiation of protein synthesis. At least some of
      these different functions may be achieved by different molecules acting in trans.

PMID- 9007059
TI  - Primary infections with HIV-1 of women and their offspring in Rwanda: findings of
      heterogeneity at seroconversion, coinfection, and recombinants of HIV-1 subtypes
      A and C.
AB  - Variation in HIV-1 genomic RNA was studied in seroconversion samples from mother
      child pairs from a Rwandan cohort. The mothers (n = 8) were heterosexually
      infected and their children (n = 6) were vertically infected by breast milk. Five
      of the children seroconverted within the same 3-month period as did their
      mothers. Highly homogeneous subtype A V3 and p17gag sequence populations were
      observed in three mother-child pairs, one of the two nontransmitting mothers, and
      one child (mean nucleotide distances 0 to 0.9%). Heterogeneous populations of
      subtype A V3 and p17gag sequences were found in one mother and a mother-child
      pair (1.4 to 2.8% for V3, 1.0 to 1.9% for p17). The second nontransmitting mother
      was infected with a heterogeneous AV1-V3/Cp17-p24 recombinant virus population
      (3. 8% for V3, 2.4% for p17). Finally, in one woman subtype C V3 sequences were
      observed, in addition to highly homogeneous subtype A V3 and p17gag sequence
      populations, also found in the child. Coexistence of subtype AV1-V3 and CV1-V3
      env sequences in the mother was confirmed in a follow-up sample. The gag gene of
      both the maternal and the child's virus population represented an A/C recombinant
      sequence (Ap17/Cp24). An infection with subtype CV1-V3/p17-p24 was found upon
      testing of three additional participants of the mother-child cohort, indicating
      that subtype C is present in Rwanda. In conclusion, heterogeneity, coinfection,
      and intersubtype recombinants are not uncommon in primary HIV-1 infections in
      Rwanda.

PMID- 9007060
TI  - Complementation of deletion of the vaccinia virus E3L gene by the Escherichia
      coli RNase III gene.
AB  - This work investigated whether the Escherichia coli RNase III gene, rnc+, could
      complement vp1080, a mutant vaccinia virus that is deleted of its E3L gene. Like
      E3L, rnc+ codes for a dsRNA binding protein that contains an additional
      nucleolytic activity. Rnc genes were cloned into the eukaryotic expression vector
      pMTVa-, expressed in COS-1 cells, and shown to be functional. Transient rescue
      experiments in HeLa cells demonstrated that the cleavage function of the rnc+
      gene was necessary for full rescue of vp1080. The rnc 70 gene, which encodes a
      product deficient in catalytic activity but still capable of binding to dsRNA,
      rescued vp1080 weakly. The rnc 105 gene, which encodes a product that cannot bind
      or cleave dsRNA, was unable to rescue vp1080. The rnc genes were also inserted
      into the E3L locus of vp1080. While recombinants containing the rnc+ gene or the
      rnc 70 gene regained the IFN resistance phenotype in RK13 cells, full host range
      of vaccinia virus was only restored in the recombinant containing the rnc+ gene.
      Thus, the ability of RNase III to process dsRNA appears to be necessary to
      restore the host range phenotype. The vp-rnc 105 recombinant behaved similarly to
      vp1080.

PMID- 9007061
TI  - Differential infectivity of two Autographa californica nucleopolyhedrovirus
      mutants on three permissive cell lines is the result of lef-7 deletion.
AB  - We isolated two Autographa californica nucleopolyhedrovirus (AcMNPV) mutants that
      have infectivity similar to that of wild-type (wt) AcMNPV in TN368 cells, but
      reduced budded virus and polyhedral inclusion body production in IPLB-SF-21 and
      SE1c cells. Restriction endonuclease analysis and sequence analysis indicated
      that 3.2-kb (77.0-79.4 m.u.) and 4.4-kb (76.7-80.1 m.u.) regions, the location of
      four major open reading frames (ORFs), pk2, ORF-247, lef-7, and chitinase, were
      deleted in mutant T295 and T297, respectively. Phenotypes of recombinant viruses
      vdel-AG, in which all four ORFs were deleted, and vlef7-AG, in which only lef-7
      was deleted, were identical to the mutants. The phenotypes of recombinant viruses
      with deletions of the other ORFs were indistinguishable from wt AcMNPV. This
      demonstrated that the deletion of lef-7 was responsible for the mutant
      phenotypes. Viral DNA synthesis in both mutant- and vlef7-AG-infected SF-21 and
      SE1c cells was reduced to less than 10% of that of wt AcMNPV-infected cells. In
      TN368 cells, DNA synthesis in mutant- and vlef7-AG-infected cells was delayed
      relative to wt-infected cells. Although lef-7 is not essential for AcMNPV
      infection in TN368 cells, it is expressed in TN368, SF-21, and SE1c cells in a
      similar manner.

PMID- 9007062
TI  - Evaluation of a live-attenuated foot-and-mouth disease virus as a vaccine
      candidate.
AB  - A variant of foot-and-mouth disease virus (FMDV) lacking the leader (L) coding
      region (A12-LLV2) was previously constructed and shown to be less virulent in
      cattle than its wild-type parent (A12-IC). In this study, cattle were tested for
      their clinical and immunological responses to subcutaneous inoculation with A12
      LLV2 or A12-IC or to intramuscular vaccination with chemically inactivated A12
      IC. Five weeks postinoculation animals were challenged by intradermal inoculation
      in the tongue with a virulent cattle-passaged virus. A12-LLV2-inoculated animals
      showed no clinical signs of disease and developed a neutralizing antibody
      response by 4 days postinoculation, whereas a companion control bovine did not
      seroconvert. After challenge, two of three inoculated animals did not develop
      lesions, but showed mild signs of infection. The third inoculated animal
      developed some lesions, but these were less severe than in the uninoculated
      control animal, which showed classical FMD. All animals inoculated with A12-IC
      developed a fever, two showed typical FMD lesions, and the companion control
      seroconverted, indicating that it had acquired infection by contact. The A12-IC
      inoculated animals and the control were protected from challenge. Animals
      vaccinated with inactivated virus showed no clinical signs of disease and
      developed a neutralizing antibody response, and the control did not seroconvert.
      Upon challenge none of the vaccinated animals developed lesions, one developed a
      fever, and the control developed FMD. These experiments demonstrate the potential
      of a rationally designed live-attenuated FMDV vaccine.

PMID- 9007063
TI  - An in vitro system for the investigation of heterologous RNA recombination.
AB  - Bacteriophage Phi6 has a genome of three segments of double-stranded RNA enclosed
      in a polyhedral procapsid. Purified procapsids are capable of the specific
      packaging of viral plus strands and the synthesis of their complementary minus
      strands. The genomic segments of Phi6 are capable of heterologous recombination.
      We have prepared an in vitro system containing purified procapsids that is
      capable of packaging plus strands of the genomic segments and synthesizing minus
      strands on these templates. The system generates heterologous recombination
      products when stimulated by having one of the plus strands incapable of serving
      as a template for minus strand synthesis. Recombinants were produced upon
      transfection of spheroplasts with the in vitro packaged and replicated RNA. Sites
      of recombination were not found to be localized in particular regions of either
      the donor or the recipient strands.

PMID- 9007064
TI  - Structure-function analysis of coxsackie B3 virus protein 2B.
AB  - Expression of poliovirus protein 2B in mammalian cells inhibits protein secretion
      and increases the susceptibility of the cells to hygromycin B, consistent with
      the increase in plasma membrane permeability seen during poliovirus infection (J.
      R. Doedens and K. Kirkegaard, EMBO J. 14, 894-907, 1995). We report here that
      expression of protein 2B of the closely related coxsackie B3 virus (CBV3) leads
      to the same biochemical alterations. Analysis of several mutant CBV3 2B proteins
      that contain mutations in a predicted cationic amphipathic alpha-helix (F. J. M.
      van Kuppeveld, J. M. D. Galama, J. Zoll, P. J. J. C. van den Hurk, and W. J. G.
      Melchers, J. Virol. 70, 3876-3886, 1996) demonstrated that the integrity of this
      domain is crucial for both biochemical functions of 2B. Mutations in a second
      hydrophobic domain (F. J. M. van Kuppeveld, J. M. D. Galama, J. Zoll, and W. J.
      G. Melchers, J. Virol. 69, 7782-7790, 1995), on the other hand, are more
      disruptive to the ability of CBV3 2B to inhibit protein secretion than to
      increase membrane permeability. Therefore, inhibition of protein secretion is not
      merely a consequence of the membrane changes that increase uptake of hygromycin
      B. The existence of mutations that interfere with virus growth but do not impair
      the ability of 2B to inhibit protein secretion or increase membrane permeability
      argues for additional functions of protein 2B.

PMID- 9007065
TI  - Isolation of the interferon-inducible RNA-dependent protein kinase Pkr promoter
      and identification of a novel DNA element within the 5'-flanking region of human
      and mouse Pkr genes.
AB  - The RNA-dependent protein kinase (PKR) is inducible by interferon (IFN) and is
      implicated in the antiviral and antiproliferative actions of IFN. We have now
      isolated human genomic clones that contain the promoter region required for
      transcription of the Pkr gene. Transient transfection analyses, using
      chloramphenicol acetyltransferase (CAT) as the reporter in constructs possessing
      various 5'-flanking fragments of the Pkr gene, led to the identification of a
      functional TATA-less promoter that directed IFN-inducible transcription of CAT.
      Sequence determination and deletion analysis of the promoter region revealed an
      element (5'GGAAAACGAAACT3') involved in IFN inducibility that corresponds to the
      consensus sequence of the IFN-stimulated response element (ISRE). Comparison of
      the promoter sequence of the human Pkr gene to that of the mouse homolog
      identified a novel element (5'GGGAAGGCGGAGTCC3') immediately upstream of the ISRE
      element which so far is unique to the human and mouse Pkr gene promoters. We have
      designated this new motif as KCS, for kinase conserved sequence. Deletion and
      substitution mutants of the Pkr promoter region showed that the ISRE element was
      required for transcriptional induction by type I IFN, whereas the KCS motif
      increased promoter activity mediated by the ISRE. Additional potential regulatory
      cis-elements were identified in the human Pkr promoter that are commonly
      associated with growth control regulation and differentiation. Other than the
      ISRE and novel KCS elements, the overall organization of potential binding sites
      for transcription factors was not well conserved between the IFN-inducible
      promoters of the human and mouse Pkr genes. The strict conservation of sequence,
      distance, and position of KCS, relative to ISRE, together with mutagenesis
      results, suggest an important functional role for the newly recognized KCS motif.

PMID- 9007066
TI  - In vivo and in vitro evidence for an anti-Rho activity induced by the phage P4
      polarity suppressor protein Psu.
AB  - The polarity suppression (Psu) protein of bacteriophage P4 causes suppression of
      transcriptional polarity in Escherichia coli by overcoming Rho termination factor
      activity. Two new psu mutants defective in polarity suppression are described.
      The psu5 mutation deletes codons 95-98 from about the middle of the gene, and the
      mutant protein is inactive. The psu6 mutation changes Phe169 to Val and encodes a
      temperature-sensitive protein. Constitutive overexpression of psu+ from a plasmid
      prevents colony formation, but overexpression of mutant genes (psu5, psu6) does
      not, suggesting that Psu disturbs essential host function(s). Rho protein
      synthesis is enhanced several-fold in cells containing wild-type Psu, due to
      readthrough at the rho attenuator, while the physical stability of Rho is
      maintained. As a consequence, Psu-producing cells accumulate significantly more
      Rho than normal cells, reminiscent of termination-defective rho mutants. The
      polarity suppression activity induced by Psu is demonstrated in vitro by the
      efficient readthrough of Rho-dependent terminators lambda tR1 and TIS2 during
      coupled transcription-translation. Purified Rho protein restores termination at
      TIS2 when added to Psu-containing reactions but NusG does not. The data support
      the hypothesis that Psu has or elicits an anti-Rho function.

PMID- 9007067
TI  - Association of a baculovirus-encoded protein with the capsid basal region.
AB  - An open reading frame homologous to AcMNPV ORF9 (ORF1629) was characterized in
      the Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis virus (OpMNPV).
      Sequence analysis indicated that the OpMNPV homolog (called ORF2) encoded a
      protein predicted to contain 545 amino acids with a molecular weight of 61 kDa.
      The first 80 amino acids did not have a counterpart in the AcMNPV homolog. The
      remainder of the ORF was poorly conserved with 29% amino acid identity overall
      with the AcMNPV ORF. However, the amino terminal 150 amino acids of AcMNPV ORF9
      demonstrated about 45% amino acid sequence identity with OpMNPV ORF2 and
      conserved runs of proline residues were present in internal regions of both
      molecules. Transcriptional mapping indicated the ORF2 transcripts were initiated
      at a late promoter sequence, ATAAG, beginning about 24 hr p.i. These transcripts
      terminated near the 3' end of the ORF2 reading frame. Antibodies were produced
      against a fusion protein derived from the bacterial gene encoding the maltose
      binding protein and most of the ORF2 sequence. These antibodies reacted with a
      protein of 69 kDa on Western blots and the protein was found to be associated
      with virions isolated from both polyhedra and budded virus. The OpMNPV ORF2
      antiserum also reacted with the AcMNPV ORF9 gene product. Immunoelectron
      microscopic analyses indicated that ORF2 was associated with the ends of the
      capsids which contain the basal structure. This end appears to be oriented away
      from both the virogenic stroma and membranes involved in intranuclear
      envelopment. In addition, as virions bud from the nucleus into the cytoplasm,
      this end also appears to be oriented away from the nuclear membrane.

PMID- 9007068
TI  - Identification of the fusion-from-without determinants of herpes simplex virus
      type 1 glycoprotein B.
AB  - Fusion-from-without (FFWO) is the rapid induction of cell fusion at high
      multiplicities of infection and in the absence of viral protein synthesis. The
      ANG path strain and several other strains of herpes simplex virus type 1 (HSV-1)
      effectively cause FFWO of Vero cells. FFWO-inducing strains of HSV-1 contain
      syncytial mutations in the gB cytoplasmic domain; however, not all strains with
      such syncytial mutations cause FFWO. By characterization of recombinant viruses
      containing chimeric gB genes, it was shown that determinants in both the gB
      ectodomain and gB cytoplasmic domain control the FFWO phenotype of HSV-1. The
      complete nucleotide sequence of the ANG path gB gene was determined. Comparison
      of the predicted amino acid sequence of ANG path gB with other HSV-1 gB sequences
      showed that the gB genes of FFWO-inducing viruses must contain both syncytial
      mutations in the gB cytoplasmic domain and the fast rate-of-entry determinant at
      residue 553 in the gB ectodomain.

PMID- 9007069
TI  - Assemblin homolog of herpes simplex virus type 1 retains proteolytic activity
      when expressed as a recombinant two-chain enzyme.
AB  - The herpes simplex virus type 1 (HSV) maturational proteinase is synthesized as a
      precursor that undergoes two autoproteolytic cleavages; one at its (M)aturational
      site, which eliminates its carboxyl "tail," and a second at its (R)elease site,
      which separates the amino proteolytic half of the precursor from its
      nonproteolytic carboxyl half. In cytomegalovirus (CMV) the proteolytic half of
      the precursor, called assemblin, undergoes a third cleavage at an (I)nternal site
      that converts it from a single-chain to a two-chain enzyme that retains activity.
      The HSV assemblin homolog has no I site and therefore does not form a counterpart
      two-chain enzyme. In the work reported here we have cloned and expressed HSV
      sequences that encode mimics of the An and Ac subunits of two-chain CMV
      assemblin. We show that when these HSV sequences are coexpressed in eukaryotic
      cells, the resulting subunits associate spontaneously to form an active two-chain
      enzyme. We also show that the two-chain HSV enzyme, like the natural one-chain
      form, retains its marked preference for HSV over CMV substrates, and that
      intertypic recombinant two-chain assemblin (e.g., HSV An/CMV Ac) does not form
      because the cross-species subunits do not interact. We conclude from these
      results that (i) there are not intrinsic structural differences in the HSV
      assemblin homolog that preclude its functioning as a CMV-like two-chain enzyme,
      (ii) the substrate selectivity shown by the single-chain HSV enzyme was not
      noticeably relaxed in the HSV two-chain mimic, and (iii) the interactive domains,
      through which the An and Ac portions of the single-chain enzymes associate,
      differ between HSV and CMV.

PMID- 9007070
TI  - Latent murine cytomegalovirus infection in macrophages.
AB  - In this study we show that macrophages (Mphi) are latently infected with murine
      cytomegalovirus (MCMV). After clearance of acute MCMV infection, the predominant
      form of chronic infection in Balb mice is latency rather than persistence.
      Peritoneal exudate cells (PECs) from latently infected Balb mice (3-9 months
      postinfection) contained MCMV genome and reactivatable virus. Adherent cells from
      both resident and thioglycollate-elicited PECs carried more MCMV DNA (measured by
      PCR) than nonadherent cells, and were selectively enriched for Mphi. FACS sorted
      F4/80(+) Mphi contained MCMV DNA, while other FACS sorted cell populations from
      PECs were never positive for MCMV DNA. MCMV reactivated from FACS sorted F4/80(+)
      Mphi in 32% of cocultures with murine embryonic fibroblasts (MEFs). Since Mphi
      carry MCMV genome and reactivatable virus, but not lytic virus, they are latently
      infected with MCMV. We determined the frequency of Mphi carrying MCMV genome in
      PECs (about 1/50,000) using a limiting dilution PCR assay. Using this frequency
      and estimates of the total amount of MCMV genome in populations, we estimate that
      latently infected Mphi carry 1-10 copies of MCMV genome. To evaluate the origin
      of latently infected Mphi, we compared the frequency of cells carrying MCMV
      genome in the resident and elicited PECs. The frequency of Mphi carrying MCMV DNA
      was the same in resident and thioglycollate-elicited PECs, despite the fact that
      there was a ninefold increase in the number of Mphi recovered after
      thioglycollate elicitation. This argued for recruitment of bone marrow-derived
      Mphi (BMMphi) carrying MCMV genome into the peritoneum during inflammatory
      responses. Consistent with this hypothesis, MCMV genome, but not persistent
      virus, was detected in bone marrow cells from latently infected mice.

PMID- 9007071
TI  - Light-dependent systemic infection of solanaceous species by cauliflower mosaic
      virus can Be conditioned by a viral gene encoding an aphid transmission factor.
AB  - Gene II of cauliflower mosaic virus (CaMV), which encodes an 18-kDa protein
      originally identified as an aphid transmission factor (ATF), influences host
      specificity in a light-dependent manner. A point mutation within the ATF gene
      that occurs in several CaMV strains was responsible for conditioning light
      dependent systemic infections. A point mutant of CaMV strain W260 that carried
      the single mutation within the ATF gene was able to systemically infect Nicotiana
      bigelovii at low light intensity (100-180 micromol m-2 sec-1), but not at a
      higher light intensity level (350-450 micromol m-2 sec-1), while the wild-type
      W260 virus could systemically infect N. bigelovii under both light conditions.
      The same point mutation also affected the stability of the amorphous CaMV
      inclusions and previous studies have shown that it abolishes transmission of CaMV
      by aphids. The point mutation within the ATF gene that mediated light-dependent
      infections was complemented by transgenic N. bigelovii plants that express the
      CaMV gene VI product, a viral protein that has been identified as a translational
      transactivator. The complementation studies indicated that the ATF gene may
      influence systemic infections through an interaction with the CaMV gene VI
      product. The ATF gene of CaMV may contribute to viral infections by regulating
      expression of downstream genes or by influencing cell-to-cell or long distance
      movement within the plant.

PMID- 9007072
TI  - Analysis of the 3' terminal sequence recognized by the Rift Valley fever virus
      transcription complex in its ambisense S segment.
AB  - A reconstituted transcription system composed of the Rift Valley fever
      phlebovirus (Bunyaviridae family) proteins L and N expressed via recombinant
      vaccinia viruses and an S-like model RNA containing the CAT gene in the antisense
      orientation, has been described previously by Lopez et al. (J. Virol., 1995, 69,
      3972-3979). We extended the use of this in vivo system to determine the sequence
      at the 3' end of the ambisense S segment recognized by the transcription complex.
      A mutational analysis of the sequences at the 3' end of the S-like genomic or
      antigenomic RNA was undertaken. The data indicated that the minimal sequence
      required for transcription resides in the 13 first 3' nucleotides of the genomic
      or antigenomic RNA. In these sequences, two regions appeared crucial: the bases
      at positions 3 to 8 and the purine at position 13. In addition, the terminal
      repeat ...GU could be deleted without affecting significantly the template
      activity of the RNA. These data support the prime and realign mechanism proposed
      recently for Bunya- and Arenaviruses

PMID- 9007073
TI  - Probing phage PRD1-specific proteins with monoclonal and polyclonal antibodies.
AB  - Four new specificity class MAbs against PRD1 proteins (P6, P7/14, P11, P18) and
      polyclonal antiserum against the minor capsid protein P5 were produced. The
      antibodies were used to analyze the phage protein distribution inside the host
      cell during infection as well as in the virion. The minor component of the
      capsid, P5, was shown to be located on the surface of the virion. The proteins
      responsible for particle infectivity were localized to the membrane fraction of
      the host cells. In addition, by detection with MAbs, genes encoding proteins P14
      and P18 were positively localized on the PRD1 genome.

PMID- 9007074
TI  - Assembly of membrane-containing bacteriophage PRD1 is dependent on GroEL and
      GroES.
AB  - Assembly of the broad-host-range bacteriophage PRD1 involves translocation of the
      virus-specific membrane to the inside of the icosahedral protein shell formed of
      trimeric coat proteins. The formation of PRD1 particles is, in addition to the
      virus-encoded assembly factors P10 and P17, dependent on GroEL/GroES chaperonins.
      The chaperonins assist in the folding of the capsid proteins P3 and P5 and in the
      assembly of viral membrane proteins.

PMID- 9007075
TI  - Strongly reduced phage Qbeta replication, but normal phage MS2 replication in an
      Escherichia coli K12 mutant with inactivated Qbeta host factor (hfq) gene.
AB  - RNA phage production was observed in Escherichia coli hfq mutant strains
      transformed with plasmids containing genomic cDNA of phages Qbeta or MS2. Qbeta
      production was reduced 5000-fold in an insertional mutant containing an omega
      cassette in the middle of hfq, but was unaffected in a mutant with the cassette
      near the end of hfq. The insertions had no effect on MS2 replication.

PMID- 9007076
TI  - Acquired fusion activity of a murine coronavirus MHV-2 variant with mutations in
      the proteolytic cleavage site and the signal sequence of the S protein.
AB  - The spike (S) protein of a nonfusogenic murine coronavirus, MHV-2, was compared
      to the S protein of a variant with fusion activity, MHV-2f. Two amino acids
      differed between the S proteins of these viruses; one was located in the signal
      sequence and the other was in the putative cleavage site. The amino acid at
      position 12 in the signal sequence was S in MHV-2 and C in MHV-2f. The amino acid
      sequence of the cleavage site of MHV-2 was HRARS, while that of MHV-2f was HRARR,
      showing one amino acid replacement at position 757. In DBT cells infected with
      MHV-2, the S protein was not cleaved, while the S protein of MHV-2f was cleaved.
      The S protein of MHV-2f expressed in a transient vaccinia virus expression system
      was cleaved and was fusogenic in contrast to the nonfusogenic activity of
      uncleaved MHV-2 S protein. Because the signal sequence is assumed to be removed
      from the mature S protein soon after synthesis, and because the S protein of MHV
      2 was expressed on the cell surface in the same way as the S protein of MHV-2f,
      the difference in the signal sequence seemed to have had little effect on the
      transportation and the fusion activity of the S protein. These results showed
      that MHV-2 does not fuse cells due to the lack of cleavage of its S protein. This
      conclusion differs from studies on the activity of syncytium formation by the S
      proteins of fusogenic MHV-JHM and -A59 strains. Possible reasons for these
      differences in fusion activity are discussed.

PMID- 9007077
TI  - Inducible expression of the 2-5A synthetase/RNase L system results in inhibition
      of vaccinia virus replication.
AB  - Studies of interferon (IFN)-treated virus-infected animal cells have revealed the
      2-5A system (2-5A synthetase/RNase L enzymes) as being responsible for virus
      inhibition only in the case of picornaviridae. To investigate whether those IFN
      induced enzymes could be responsible for inhibition of poxvirus replication, we
      have generated recombinant vaccinia viruses (VV) containing the corresponding
      genes (VV-2-5AS and VV-RL, respectively). RNase L produced in cells infected with
      VV-RL leads to rRNA degradation and inhibition of virus protein synthesis, which
      correlates with about 92% reduction in virus yields by 48 hr after infection.
      Combined expression of this enzyme with 2-5A-synthetase further inhibits virus
      yields. The pattern of rRNA fragments produced by infection with viruses VV-RL
      and/or VV-2-5AS is the characteristic for activation of the 2-5A pathway by IFN
      treatment. Combined infection of VV-RL together with vesicular stomatitis virus
      (VSV) demonstrates this inhibition to be specific for VV and not due to a general
      effect. Breakdown of rRNA is largely due to the recombinant vector-derived
      enzyme, since a C-terminal deletion mutant of RNase L is inactive and the extent
      of rRNA degradation induced by infection with VV-RL is similar in cells treated
      or not with IFN. Moreover, the anti-VV effects of RNase L is also observed in a
      cell line lacking the endogenous ds RNA-dependent protein kinase (PKR). Thus, our
      findings provide direct evidence for antiviral activity of the 2-5A system on
      poxviruses.

PMID- 9007078
TI  - Characterization of a disassembly deficient mutant of cowpea chlorotic mottle
      virus.
AB  - An understanding of virus disassembly requires a detailed understanding of the
      protein-protein and protein-nucleic acid interactions which stabilize the virion.
      We have characterized a mutant of cowpea chlorotic mottle virus [cpR26C (coat
      protein R26C)] that displays increased virion stability and is abnormal in virion
      disassembly when purified under nonreducing conditions. Reduced virions are
      infectious, whereas nonreduced virions are noninfectious. The cpR26C mutant
      virions purified under nonreducing conditions resist disassembly in 0.5 M CaCl2,
      pH 7.5. The nonreduced cpR26C mutant virions swell in neutral pH conditions (pH
      7.5) but do not disassociate when the ionic strength is increased. In contrast,
      wild-type virions or cpR26C mutant virions isolated under reducing conditions
      completely disassociate into the RNA and capsid protein components at pH 7.5 and
      high ionic strength (i > 1.0). Sequence analysis of the cpR26C mutant identified
      a single C to U nucleotide change at position 1435 of RNA 3 (position 86 of RNA
      4), which results in a arginine to cysteine change at position 26 of the coat
      protein. The cpR26C mutant provides an ideal chemical switch for examining virion
      assembly and disassembly.

PMID- 9007079
TI  - Sindbis virus infection of neonatal mice results in a severe stress response.
AB  - Neonatal mice were infected with virus derived from a molecular clone of a
      laboratory strain of Sindbis virus, TRSB. The resulting acute fatal infection was
      typified by few if any of the classic hallmarks of encephalitis, very high levels
      of interferon-alpha/beta (IFNalphabeta), and lesions in the thymus and
      hematopoietic tissues usually associated with a severe stress response. Infection
      with an attenuated mutant of TRSB, which harbors a single amino acid change in
      the E2 surface glycoprotein (TRSBr114), was characterized by encephalitis,
      reduced mortality, low levels of IFNalphabeta, and no thymic pathology (J.
      Trgovcich, J. F. Aronson, and R. E. Johnston, 1996, Virology 224, 73-83). Here we
      report that infection of neonatal mice with TRSB, but not TRSBr114, resulted in
      induction of high levels of tumor necrosis factor-alpha as well as high and
      sustained levels of adrenalcorticotropin-releasing hormone and corticosterone.
      This syndrome of potentially toxic cytokine and stress hormone induction
      correlates with lethal Sindbis virus infection and constitutes a previously
      unrecognized aspect of Sindbis virus pathogenesis in mice.

PMID- 9007080
TI  - Fiber genes of adenoviruses with tropism for the eye and the genital tract.
AB  - We have characterized the fibergenes of adenovirus type 19p (Ad19p), Ad19a, and
      Ad37 by sequencing. The fiber genes of Ad19a and Ad37 are identical and only five
      amino acids differ comparing Ad19a/Ad37 with Ad19p. Based on the translated
      sequences we calculated the isoelectrical points (Ips) and found that the fiber
      knobs of Ad19p, Ad19a, and Ad37 together with Ad8 display the highest Ips of all
      so far characterized. Two regions within the fiber knob with unusually basic
      characteristics have been identified. Sequence alignments revealed that the
      corresponding regions in other fiber knobs are highly antigenic in pepscan
      analysis and of importance for hemagglutination. Only two positions differ in the
      knobs comparing Ad19a/Ad37 with Ad19p. Hence, either of these or both amino acid
      residues should be expected to be responsible for the observed differences in
      hemagglutination between Ad19p and Ad19a/Ad37. Moreover, we have found two amino
      acids (Ala227 and Lys252) that are unique in their respective position in Ad19p,
      Ad19a, Ad37, and Ad8. Three amino acids (Lys236, Lys240, and Asn251) are unique
      in their respective position in Ad19a and Ad37, that manifest a tropism for the
      genital tract. All five amino acids colocalize within one of the two basic
      regions.

PMID- 9007081
TI  - ORF 3 of lactate dehydrogenase-elevating virus encodes a soluble, nonstructural,
      highly glycosylated, and antigenic protein.
AB  - Open reading frame (ORF) 3 of the genome of lactate dehydrogenase-elevating virus
      (LDV), strain P, was cloned into the plasmid pcDNAI/Amp and in vitro transcribed
      and translated. Translation of ORF 3 yielded a soluble protein of the expected
      size (about 21 kDa). When synthesized in the presence of endoplasmic reticulum
      (ER) membranes the resulting glycoprotein of about 36 kDa became associated with
      the membranes. However, disruption of the ER vesicles by incubation in carbonate
      buffer, pH 11.5, resulted in the release of the protein from the membranes.
      Hydrophobic moment analysis of the ORF 3 protein indicated the absence of any
      potential transmembrane segments, except for a N-terminal signal peptide, but no
      cleavage of the signal peptide was observed during membrane-associated in vitro
      synthesis. The ORF 3 protein elicited a strong antibody response in infected
      mice. The antibodies from infected mice as well as a monoclonal antibody
      specifically precipitated the in vitro-synthesized ORF 3 protein, but no protein
      from LDV virions. The overall results suggest that the ORF 3 protein is a
      nonstructural, highly glycosylated, and antigenic glycoprotein that is probably
      soluble and secreted or at most only weakly associated with membranes via the
      signal peptide.

PMID- 9007082
TI  - Proteolytic processing of Chlorella virus CVK2 capsid proteins.
AB  - Chlorella virus CVK2 particles contain several capsid proteins that are
      selectively released by treatment with 4 M urea. Seven of them (Vp52, Vp45, Vp41,
      Vp25, Vp20.5, Vp20, and Vp16.2) have been identified based on amino acid
      sequences at the N-terminus. Comparison of the amino acid sequences with the
      corresponding ORFs deduced from the nucleotide sequence of PBCV-1, the prototype
      member of Phycodnaviridae, revealed that the CVK2 proteins were processed at the
      N-terminal region by two different proteolytic activities.

PMID- 9007083
TI  - Repression of p53 transcriptional activity by the HPV E7 proteins.
AB  - The major transforming protein of human papillomaviruses (HPVs) is encoded by the
      E7 gene. This protein cooperates with activated oncogenes to transform primary
      rodent cells and with the viral E6 gene to immortalize primary human
      keratinocytes. Numerous cellular targets of HPV E7 have now been identified
      including pRb, p107, cyclin A, TATA box binding protein (TBP), and members of the
      AP-1 transcription factor family. As with Adenovirus E1a, many of these
      interactions are important for the ability of E7 to transform cells. Recent
      studies have demonstrated that Adenovirus E1a can also inhibit the
      transcriptional activity of the cellular tumor suppressor protein, p53. We have
      performed a series of analyses to determine whether HPV E7 proteins share this
      characteristic. We show that HPV E7 proteins derived from both benign and tumor
      associated HPV types are able to inhibit p53 transcriptional activity. Mutational
      analysis of the HPV-16 E7 protein reveals that a key domain involved in mediating
      this activity is the casein kinase II (CKII) recognition site, which has been
      shown to modulate E7 binding to TBP. We further show that E7 does not bind to p53
      directly, but will do so in the presence of exogenously added TBP and that this
      binding is increased following CKII phosphorylation. These results suggest that
      the E7-TBP interaction may be responsible for inhibiting p53 transcriptional
      activity.

PMID- 9007085
TI  - Targets for the therapeutic action of interferon-beta in multiple sclerosis.

PMID- 9007084
TI  - Natural endogenous reverse transcription of simian immunodeficiency virus.
AB  - It has been demonstrated that human immunodeficiency virus type 1 (HIV-1) virions
      are biochemically active particles, within which reverse transcription can take
      place even in physiological microenvironments. This process has been termed
      "natural endogenous reverse transcription" (NERT). In this report, we demonstrate
      that purified virions of simian immunodeficiency virus (SIV) also contain virus
      specific DNA, which resulted from partial reverse transcription. Further, viral
      DNA synthesis could be initiated in SIV virions in the presence of polyamines and
      deoxyribonucleoside triphosphates (dNTPs), at physiological concentrations. The
      viral infectivity upon initially quiescent cells was significantly increased,
      when the levels of intravirion reverse transcripts were modulated. These data
      suggest that NERT of SIV may play an important role for SIV pathogenesis and
      transmission. In contrast to HIV-1, these hypotheses may be further directly
      investigated by in vivo model systems.

PMID- 9007086
TI  - Apolipoprotein E and inclusion body myositis.

PMID- 9007088
TI  - Selegiline and mortality in Parkinson's disease.

PMID- 9007087
TI  - Genetic factors in Alzheimer's disease: a review of recent advances.

PMID- 9007089
TI  - Interferon beta-1b inhibits gelatinase secretion and in vitro migration of human
      T cells: a possible mechanism for treatment efficacy in multiple sclerosis.
AB  - Treatment with interferon beta-1b has substantial clinical benefit in the
      demyelinating disease multiple sclerosis, yet the mechanism of action in the
      disease remains largely unknown. Gelatinase A (matrix metalloproteinase-2, 72-kd
      gelatinase) and B (matrix metalloproteinase-9, 92-kd gelatinase) are matrix
      metalloproteinases capable of enzymatic digestion of subendothelial basement
      membrane constituents. In human T cells, interleukin-2 induces gelatinase
      secretion and enhances gelatinase-dependent migration across an artificial
      basement membrane-like layer in vitro. Pretreatment of T cells with interferon
      beta-1b for 48 hours decreased interleukin-2-induced gelatinase production and
      secretion as determined by zymography. In parallel to the downregulation of
      gelatinase secretion, pretreatment with interferon beta-1b inhibited T-cell
      migration across the basement membrane in vitro by up to 90%, but had only a
      minor impact on cell locomotion per se. For both gelatinase secretion and T-cell
      migration, the inhibitory effect mediated by exposure to interferon beta-1b was
      dose dependent. Fluorescence-activated cell sorter analysis also showed that
      interferon beta-1b downregulates the interleukin-2 receptor alpha-chain and
      lowered the affinity of interleukin-2 to the cell surface by 30%, which may
      represent an additional mechanism for the observed effects of interferon beta-1b.
      The dramatic effects of interferon beta-1b on gelatinase expression and migration
      raise the possibility that its beneficial effects in multiple sclerosis may
      result from interference with the capacity of activated T cells to traverse the
      basement membrane and migrate to the central nervous system.

PMID- 9007091
TI  - Apolipoprotein E and apolipoprotein E messenger RNA in muscle of inclusion body
      myositis and myopathies.
AB  - Sporadic inclusion body myositis and the hereditary inclusion body myopathies are
      severe, progressive muscle diseases, characterized pathologically by vacuolated
      muscle fibers containing paired helical filaments. We immunostained muscle biopsy
      specimens from sporadic inclusion body myositis, hereditary inclusion body
      myopathy, disease control, and normal patients with several antibodies against
      apolipoprotein E (ApoE). Approximately 80 to 90% of the vacuolated muscle fibers
      of sporadic inclusion body myositis contained well-defined, strongly
      immunoreactive ApoE inclusions. In hereditary inclusion body myopathy, only rare
      vacuolated fibers had immunoreactive inclusions, whereas most had diffuse
      cytoplasmic ApoE immunoreactivity. Ultrastructurally, ApoE immunoreactivity in
      sporadic myositis was localized mainly to the paired helical filaments. By
      contrast, in the hereditary form, ApoE immunoreactivity occurred on material in
      close proximity to the paired helical filaments, but never was on the paired
      helical filaments. In both muscle diseases, ApoE was also on the 6- to 10-nm
      filaments and amorphous material. In the sporadic form, ApoE-immunoreactive
      deposits colocalized with Congo red-positive deposits; however, in muscle fibers
      from patients with hereditary disease there was no congophilia. ApoE messenger
      RNA was not detectable in muscle fibers from patients with hereditary or sporadic
      disease but was expressed abundantly in muscle macrophages. In all control and
      inclusion body myositis or myopathy biopsy specimens, ApoE immunoreactivity was
      strong at the postsynaptic domain of neuromuscular junctions; nonjunctional
      regions of normal fibers were negative for ApoE. ApoE immunoreactivity occurred
      diffusely in regenerating muscle fibers, a subset of which had detectable ApoE
      messenger RNA.

PMID- 9007090
TI  - Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on
      matrix metalloproteinase-9.
AB  - In multiple sclerosis (MS), the influx of activated T lymphocytes into the brain
      parenchyma leads to the subsequent damage of oligodendrocytes, the cells that
      produce central nervous system (CNS) myelin. We report here that interferon beta
      1b (IFNbeta-1b), a drug shown to be efficacious in the treatment of patients with
      MS, decreases the in vitro migration of activated T lymphocytes through
      fibronectin (FN), a major component of the basement membrane that surrounds
      cerebral endothelium. At 1,000 IU/ml, IFNbeta-1b reduced the migratory rate to
      that of unactivated T cells. In contrast, IFNgamma at 1,000 IU/ml, which caused a
      similar decrease (25%) in the proliferation rate of T lymphocytes as IFNbeta-1b,
      did not affect migration. All T-lymphocyte subsets and natural killer (NK) cells
      were demonstrated by flow cytometry to be equally affected by IFNbeta-1b
      treatment. 125I-Western blot analyses revealed that IFNbeta-1b treatment resulted
      in a marked reduction of the ability of T cells to cleave FN. The substrate
      degrading capability of T lymphocytes was shown to be due predominantly to the
      activity of a 92-kd matrix metalloproteinase, MMP-9, whose levels were decreased
      by IFNbeta-1b. We suggest that the clinical benefits of IFNbeta-1b treatment in
      MS patients may be in part a result of the ability of this drug to significantly
      decrease MMP-9 activity, leading to a reduction of T-lymphocyte infiltration into
      the CNS.

PMID- 9007093
TI  - Decreased striatal monoaminergic terminals in olivopontocerebellar atrophy and
      multiple system atrophy demonstrated with positron emission tomography.
AB  - We used [11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular
      monoamine transporter (VMAT2), with positron emission tomography to study
      striatal monoaminergic presynaptic terminals in 4 patients with multiple system
      atrophy, 8 with sporadic olivopontocerebellar atrophy, and 9 normal control
      subjects. Specific binding in the striatum was significantly reduced in the
      multiple system atrophy patients as compared with the normal control group, with
      average reductions of 61% in the caudate nucleus (p = 0.002) and 58% in the
      putamen (p = 0.009). Smaller reductions were found in the sporadic
      olivopontocerebellar atrophy group, averaging 26% in the caudate nucleus (p =
      0.05) and 24% in the putamen (p = 0.11). Mean blood-to-brain
      [11C]dihydrotetrabenazine transport (K1) was significantly different between
      groups only in the cerebellum, with values for the sporadic olivopontocerebellar
      atrophy group diminished compared with the normal control group. Cerebellar K1
      was not significantly decreased in the multiple system atrophy group. The finding
      of reduced striatal VMAT2 in sporadic olivopontocerebellar atrophy patients
      suggests nigrostriatal pathology, indicating that some may later develop
      symptomatic extrapyramidal disease.

PMID- 9007092
TI  - Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging.
AB  - We present development and human application of a method for determining the
      regional cerebral density of the type 2 vesicular monoamine transporter (VMAT2)
      using positron emission tomography (PET) and [11C]dihydrotetrabenazine (DTBZ).
      Previous animal studies indicate striatal VMAT2 density is linearly related to
      the integrity of substantia nigra dopamine neurons and is not subject to drug- or
      lesion-compensatory regulation. In the present studies, kinetic compartmental
      modeling was employed to estimate blood-brain [11C]DTBZ transport (K1) and VMAT2
      binding site density (tissue-to-plasma DTBZ distribution volume, DV) from the
      cerebral and plasma DTBZ time courses after intravenous tracer injection. In
      controls, we found reductions of putamen DTBZ DVwith advancing age, corresponding
      to losses of 0.77% per year in specific VMAT2 binding. Parkinson's disease (PD)
      patients had reduction in specific DTBZ DV in the putamen (-61%) and in the
      caudate nucleus (-43%). There was no overlap of lowest specific putamen DTBZ DV
      between individual elderly controls and PD patients. The present results indicate
      the suitability of [11C]DTBZ PET for objective quantification of nigrostriatal
      integrity, including evaluation of PD progression and its possible therapeutic
      modification.

PMID- 9007095
TI  - A high-resolution three-dimensional T1-weighted gradient echo sequence improves
      the detection of disease activity in multiple sclerosis.
AB  - In this study, we performed a post-contrast magnetization-prepared rapid
      acquisition gradient echo (MP RAGE) sequence with subsequent reconstruction of
      axial slices with 5-, 3-, and 1-mm thickness in 26 patients with multiple
      sclerosis (MS) to investigate the disease activity going on below the resolution
      of conventional scans. One hundred three enhancing lesions were detected using MP
      RAGE reconstructed with 1-mm-thick slices, 93 using MP RAGE reconstructed with 3
      mm-thick slices and 82 using MP RAGE reconstructed with 5-mm-thick slices. The
      detection rate using 1-mm MP RAGE was 25.6% higher compared with 5-mm MP RAGE and
      12% higher compared with 3-mm MP RAGE. Using 1-mm MP RAGE, we detected five
      enhancing lesions in 2 of the 12 patients (16.6%) who showed no enhancing lesions
      on the 5-mm MP RAGE and one enhancing lesion in 1 of the 10 patients (10%) who
      showed no enhancing lesions on the 3-mm MP RAGE. The increased sensitivity of 1
      mm MP RAGE over the other two reconstruction slice thicknesses was due to
      improved detection of small lesions, located mainly in cortical/subcortical
      areas. These data indicate that the size of enhancing lesions in MS is highly
      variable, and that a significant proportion of disease activity goes undetected
      when performing conventional scans.

PMID- 9007094
TI  - Unusual clinical presentations of cortical-basal ganglionic degeneration.
AB  - Cortical-basal ganglionic degeneration classically presents predominantly as a
      motor disorder with a unique constellation of histological alterations
      characterized by the presence of neuronal loss and gliosis in a selective
      distribution, swollen achromasic neurons, and extensive deposition of abnormal
      tau in neurons and glia. We now report 3 patients with this distinctive pathology
      who presented with cognitive changes and only mild or delayed motor symptoms. In
      2 patients with severe dementia, pathological changes were extensive in the
      anterior frontal lobe, amygdala, and hippocampus. In a third patient who had an
      isolated speech disturbance for 5 years before developing the more typical motor
      features of cortical-basal ganglionic degeneration, the most severe changes were
      observed in the left motor cortex and adjacent Broca's area. It is therefore
      apparent that the histological changes of cortical-basal ganglionic degeneration
      result in a variety of clinical presentations depending on the topography of the
      lesions. On this basis we conclude that cortical-basal ganglionic degeneration
      should be considered in the differential diagnosis of language disturbances and
      dementia, particularly when the latter is accompanied by frontal lobe
      symptomatology, early speech alterations, or parkinsonism.

PMID- 9007096
TI  - Low brain GABA level is associated with poor seizure control.
AB  - Low gamma-aminobutyric acid (GABA) concentrations in the cerebrospinal fluid are
      seen in a variety of epileptic syndromes. Low GABA levels outside of the
      epileptic focus may facilitate spread of discharges beyond the focus. In vivo
      measurements of GABA were made by 1H spectroscopy using a 2.1-T magnetic
      resonance imager-spectrometer and an 8-cm surface coil to measure a 14-cm3 volume
      in the occipital lobe. Patients with complex partial seizures had lower GABA
      levels (1.03 mmol/kg of brain; 95% confidence interval [CI], 0.95-1.12; n = 28; p
      < 0.02) than did subjects without epilepsy (1.18; 95% CI, 1.13-1.24; n = 19).
      There was a significant association between low GABA levels and recent seizures
      (correlation coefficient of 0.548, p < 0.01, df of 32). Conversely, patients with
      well-controlled seizures had higher brain GABA levels than did patients with
      recent seizures. Patients with seizures within a day of the measurement had lower
      GABA levels (0.92 mmol/kg; 95% CI, 0.78-1.06; n = 7) than did patients who were
      seizure free for 5 years or longer (1.28; 95% CI, 1.09-1.47; n = 4). Poor seizure
      control is associated with low brain GABA levels.

PMID- 9007097
TI  - The clinical phenotype of two missense mutations in the presenilin I gene in
      Japanese patients.
AB  - We report the clinical and neuropathologic phenotypes associated with two
      different missense mutations in the presenilin 1 (PS-1) gene in Japanese patients
      with early-onset familial Alzheimer's disease (FAD). In the AM/JPN1 pedigree a
      missense mutation (C-->T) was found at nucleotide 1102, which is predicted to
      cause an alanine-to-valine missense substitution at codon 260. In this family,
      the disease had a mean age of onset of 40.3 years and an indolent course (range,
      8-19 years). Neuropathologic studies in 3 members of this pedigree showed
      widespread senile plaques, neurofibrillary tangles, and neuronal loss, as well as
      abundant perivascular subpial amyloid deposits in the Virchow-Robin spaces and
      the presence of Pick-like intraneuronal inclusions in the dentate gyrus. In the
      second pedigree, transmitting a C-->T nucleotide substitution at position 1027,
      leading to the missense mutation of alanine to valine at codon 285, the disease
      had a later onset (mean, 51 years) but a more rapid course. Comparison of the
      disease phenotypes associated with other missense mutations in exon 9 of PS-1
      reveals no clinical or pathological phenotype, which uniquely distinguishes
      Alzheimer's disease associated with PS-1 mutations from other forms of early
      onset FAD, implying that direct mutation screening is required to identify these
      cases.

PMID- 9007098
TI  - Horizontal canal benign paroxysmal positioning vertigo (h-BPPV): transition of
      canalolithiasis to cupulolithiasis.
AB  - We report on 2 patients with typical features of horizontal canal benign
      paroxysmal positioning vertigo (h-BPPV). A vigorous head positioning in these
      patients from supine to a bending-over, head-on-the-knees position reversed the
      direction of nystagmus from geotropic initially to ageotropic when rolling the
      head from side to side while supine. We explain this by a conversion of
      canalolithiasis into cupulolithiasis and conclude that (1) canalolithiasis and
      cupulolithiasis may sequentially occur in the same semicircular canal with
      subsequent positioning maneuvers and (2) positional nystagmus beating toward the
      uppermost ear is not a pathognomonic sign of central vestibular disturbance but
      can indicate occasional cupulolithiasis.

PMID- 9007099
TI  - Clinical and pathological features in hydrocarbon-induced parkinsonism.
AB  - A neuropathological examination was performed on a patient with parkinsonism
      induced by prolonged exposure to a mixture of aliphatic hydrocarbons, mainly n
      hexane and halogenated compounds. The patient developed a rapid-course disease
      that progressed even after withdrawal from the toxic exposure. Pathological
      examination and immunohistochemical analysis of the brain revealed severe and
      widespread dopaminergic neuronal loss, associated with severe gliosis, in the
      substantia nigra, and almost complete loss of tyrosine hydroxylase immunostaining
      in the striatum. No Lewy bodies were detected. Neuronal loss was also observed in
      the periaqueductal gray matter, locus ceruleus, and pedunculopontine nucleus.
      These changes, combined with the moderate anemia due to marrow suppression, and
      the mild axonal neuropathy observed in vivo, are suggestive of a hydrocarbon
      toxic insult.

PMID- 9007100
TI  - Muscular dystrophy associated with beta-Dystroglycan deficiency.
AB  - beta-Dystroglycan, a 43-kd transmembrane dystrophin-associated glycoprotein,
      plays an important role in linking dystrophin to the laminin-binding alpha
      dystroglycan. alpha-/beta-Dystroglycan is encoded by a single gene on chromosome
      3p21 and ubiquitously expressed in muscle and nonmuscle tissues. No known human
      diseases have been mapped to this locus. Here, we describe the selective
      deficiency of beta-dystroglycan in a 4-year-old Saudi boy with muscular
      dystrophy. The patient had a borderline elevation of serum creatine kinase level
      and early-onset proximal symmetrical muscle weakness and wasting without calf
      hypertrophy. The milder phenotype may suggest a secondary deficiency of beta
      dystroglycan; however, the unique immunofluorescence labeling suggests that the
      patient may present a novel form of muscular dystrophy.

PMID- 9007101
TI  - Bilateral brachial plexus neuritis following parvovirus B19 and cytomegalovirus
      infection.
AB  - A man, 23 years of age, had a typical erythema infectiosum, complicated by a
      severe bilateral brachial plexus neuritis. Motor function recovered slowly and
      only partially after 6 months. An infection by human parvovirus B19 was
      demonstrated, with strongly positive and gradually declining IgM antibodies and
      viral DNA detectable in serum for more than 3 months. There was also clear
      evidence of a recent infection by cytomegalovirus. The interaction between these
      two viruses could be responsible for this rare and severe complication of common
      infections in this patient.

PMID- 9007102
TI  - Wide range in age of onset for chromosome 1--related familial Alzheimer's
      disease.
AB  - Mutations in three different genes on chromosomes 1, 14, and 21 cause autosomal
      dominant forms of familial Alzheimer's disease (FAD). Most result in an early
      onset phenotype. However, several kindreds of Volga German ancestry have the same
      chromosome 1 gene mutation and demonstrate a relatively older mean age of onset
      and include individuals with late age of onset. In these families, the mean age
      of onset is 54.9 +/- 8.4 years (range, 40-75 years), mean age at death is 65.9 +/
      10.2 years (range, 43-88 years), and mean disease duration is 11.3 +/- 4.6 years
      (range, 5-23 years). This contrasts with a group of 7 families with chromosome 14
      mutations in which the mean age of onset is 44.8 +/- 4.8 years (range, 30-55
      years), mean age at death is 52.6 +/- 5.7 years (range, 39-65 years), and mean
      disease duration is 7.6 +/- 3.2 years (range, 2-17 years). (All means are
      significantly different in the 2 groups of families, p < 0.005.) In the
      chromosome 1 families, 7 persons (16%) had an age of onset at or older than 65
      years and 22 (54%) survived to age 65 or older versus none in the chromosome 14
      families. An example of probable nonpenetrance of disease at age 89 was also
      found in a chromosome 1 kindred. It is concluded that, unlike the chromosome 14
      gene, mutations in the chromosome 1 FAD gene may result in individuals with a
      late age of onset overlapping with the more common sporadic form of the disease
      occurring in the general population. In light of the great variability in age of
      onset in persons with identical mutations, study of the genetic and environmental
      factors contributing to delayed onset of disease in chromosomal 1 FAD kindreds
      will be an important area for further investigation. Apolipoprotein E genotype
      may be one such factor that plays a partial role in this variability.

PMID- 9007103
TI  - Surgical management of superficial siderosis following cervical nerve root
      avulsion.
AB  - Neurosensory hearing loss, ataxia, spastic paraparesis, sphincter dysfunction,
      somatosensory disturbances, and cognitive effects are associated with superficial
      siderosis of the central nervous system caused by chronic intrathecal bleeding.
      We describe superficial siderosis that developed more than a decade following
      traumatic brachial nerve root avulsion. While cerebrospinal fluid analysis
      indicated chronic intrathecal bleeding, angiography did not localize a specific
      source. Surgical intervention that included repair of a meningeal diverticulum
      and venous cauterization resulted in overall reduction, but not complete
      elimination, of central nervous system bleeding.

PMID- 9007104
TI  - Loss of tuberin from cerebral tissues with tuberous sclerosis and astrocytoma.
AB  - We studied the expression of tuberin, the TSC2 gene product, in cerebra with or
      without tuberous sclerosis. Tuberin was abundant in the gray matter of normal
      cerebra, but was undetectable in the subependymal astrocytomas from 3 patients
      with tuberous sclerosis. In 1 patient, cortical tubers and normally appearing
      cortical tissue also showed a marked loss of tuberin. These results indicate the
      critical role of tuberin in the neuropathology of tuberous sclerosis.

PMID- 9007105
TI  - Differences between multiple system atrophy and olivopontocerebellar atrophy.

PMID- 9007106
TI  - Study design problems of DATATOP study analysis.

PMID- 9007107
TI  - Biopsy findings link multifocal motor neuropathy to chronic inflammatory
      demyelinating polyneuropathy.

PMID- 9007108
TI  - Specificity of ethanol in essential tremor.

PMID- 9007109
TI  - The "round the houses" sign in progressive supranuclear palsy.

PMID- 9007110
TI  - Importance of magnetic resonance imaging and gadolinium enhancement.

PMID- 9007111
TI  - Current therapy of small cell lung cancer.

PMID- 9007112
TI  - Non-small cell lung cancer: slow but definite progress.

PMID- 9007113
TI  - Paclitaxel, carboplatin, and oral etoposide in the treatment of small cell lung
      cancer.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is active in
      previously untreated patients with small cell lung cancer (SCLC). We evaluated
      the toxicity and efficacy of a 1-hour infusion of paclitaxel added to a
      combination regimen of carboplatin and etoposide in a phase II trial for the
      treatment of patients with SCLC. Thirty-eight patients with previously untreated
      SCLC were treated with paclitaxel 135 mg/m2 (1-hour intravenous infusion), day 1;
      carboplatin at area under the concentration-time curve of 5, day 1; and oral
      etoposide 100 and 50 mg (alternating days), days 1 to 10. Treatment cycles were
      repeated every 21 days for a total of four courses. Patients with limited-stage
      disease received radiation therapy (4,500 cGy in 25 fractions) concurrently with
      the last two courses of chemotherapy. This outpatient combination was easily
      tolerated. Grade 3 or 4 leukopenia was experienced in only 8% of courses; grades
      3 and 4 thrombocytopenia and anemia were also infrequent. Nonhematologic toxicity
      was uncommon, with the exception of transient esophagitis, which occurred in six
      of 15 patients (grade 3 in five patients, grade 4 in one) receiving concurrent
      chemoradiotherapy. Of 35 evaluable patients, 29 (83%) achieved a response to
      treatment. The complete response rate was 29% (40% in patients with limited-stage
      disease). Median survival was 7 months for patients with extensive-stage disease
      and 17 months in limited-stage patients. Prophylactic whole brain irradiation was
      not used, and seven patients developed brain metastases as their initial site of
      relapse. The combination of 1-hour paclitaxel, carboplatin, and extended oral
      schedule etoposide is feasible and well tolerated at the doses administered in
      this phase II trial. This treatment was highly active and the results are
      comparable to other standard regimens. Increased doses of both paclitaxel and
      carboplatin could probably be tolerated and are currently being evaluated.
      Precise definition of the role of paclitaxel in the treatment of SCLC will
      require randomized studies.

PMID- 9007114
TI  - Phase I study of cisplatin, etoposide, and paclitaxel in patients with extensive
      stage small cell lung cancer: a University of Colorado Cancer Center study.
AB  - This phase I study investigated the maximum tolerated dose of cisplatin,
      etoposide, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in
      18 patients with advanced small cell lung cancer. Cisplatin (80 mg/m2) and
      etoposide (50 or 80 mg/m2 intravenously and 100 or 160 mg/m2 orally) were infused
      concomitantly 30 minutes after a 3-hour infusion of paclitaxel (135, 175, or 200
      mg/m2). This order of administration was known to cause less toxicity than the
      reverse order. Granulocyte colony-stimulating factor was given as necessary.
      Overall, complete responses were observed in 33% of evaluable patients and
      partial responses were seen in 67%. No patient progressed during therapy. Median
      survival exceeded 12 months, with 53% of patients alive at 1 year. Untreated
      patients in similar health survive approximately 6 to 16 weeks. Hematologic
      toxicities were seen most frequently, and neutropenia was seen most often and was
      the most severe. Febrile neutropenia occurred in one patient; grade 4
      thrombocytopenia did not occur at all. Nonhematologic toxicity was mild. Nausea
      and vomiting generally were well controlled, and there were no instances of
      severe allergic reaction. Although the maximum tolerated dose has not yet been
      defined, one of two patients in the group receiving the highest doses encountered
      a dose-limiting toxicity. Thus, we expect to recommend the following dosages for
      further study: cisplatin 80 mg/m2, etoposide 80 mg/m2, and paclitaxel 175 mg/m2.
      All patients had an objective response and one third had a complete response,
      compared with 10% of patients in most series. We conclude that paclitaxel can be
      added safely to full doses of cisplatin and etoposide with encouraging efficacy,
      and recommend a randomized trial be undertaken to compare the two-drug regimen
      with the three-drug regimen.

PMID- 9007115
TI  - Single-agent paclitaxel in the treatment of small cell lung cancer.

PMID- 9007116
TI  - The North American experience with paclitaxel combined with cisplatin or
      carboplatin in lung cancer.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a new
      cytotoxic chemotherapeutic agent with a novel mechanism of action. Single-agent
      paclitaxel studies have shown promising activity in both small cell and non-small
      cell lung cancers. In non-small cell lung cancer, response rates of 22% to 26%
      and 1-year survival rates of 40% were reported with both 3-hour and 24-hour
      infusions of paclitaxel. In small cell lung cancer, 24-hour infusions produced
      response rates of 61%. These data indicate that paclitaxel is one of the most
      active agents for all lung cancer patients. Combination studies demonstrated that
      paclitaxel could be combined with either cisplatin or carboplatin at full doses
      using either a 3-hour or a 24-hour infusion schedule. Response rates with these
      combinations have been high, usually 40% to 50%, which are higher than with any
      of the drugs used alone. Neutropenia is the most frequent toxicity and occurs
      less frequently with the 3-hour infusion. Thrombocytopenia occurred less
      frequently than expected. One completed randomized study showed that the
      paclitaxel/cisplatin regimen was superior to the etoposide/cisplatin regimen with
      respect to response rate and survival. Additional randomized studies are
      necessary to determine whether the combinations are superior to single-agent
      paclitaxel, to define the optimal dose with the 3-hour infusion schedule, to
      define the optimal schedule (3 hours v 24 hours), and to determine whether
      paclitaxel can be combined with other new agents.

PMID- 9007117
TI  - Early phase studies with paclitaxel/low-dose carboplatin in patients with solid
      tumors.
AB  - In preparation for the design of phase II studies in lung cancer, low-dose
      carboplatin, fixed at a target area under the concentration-time curve (AUC) of
      4.0 or 4.5 mg x min/mL, has been combined with escalating doses of paclitaxel
      (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in a series of studies to
      establish the maximum tolerated dose of the combination. In patients who had
      received prior chemotherapy, the maximum tolerated paclitaxel dose was 135 mg/m2
      (carboplatin target AUC 4.0); the dose-limiting toxicity was febrile neutropenia.
      Without granulocyte colony-stimulating factor support in chemotherapy-naive
      patients (carboplatin target AUC 4.5), and with granulocyte colony-stimulating
      factor in chemotherapy-pretreated patients, the current paclitaxel dose is 290
      mg/m2. The maximum tolerated dose has not been defined. In a study in which
      paclitaxel was given by 1-hour infusion with carboplatin (target AUC 4.5), a 205
      mg/m2 dose was poorly tolerated. No evidence of pharmacokinetic interactions
      between paclitaxel and carboplatin was found. Twenty-one evaluable patients with
      lung cancer have been treated to date. There have been two partial responses, one
      minor response, and 10 patients with stable disease at paclitaxel doses of 100 to
      270 mg/m2.

PMID- 9007118
TI  - Schedule- and dose-intensified paclitaxel as weekly 1-hour infusion in pretreated
      solid tumors: results of a phase I/II trial.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been studied
      primarily on a 3-week schedule as a 3-, 24-, or 96-hour infusion at doses ranging
      from 135 to 250 mg/m2. The observed toxicity profile seems to be both dose and
      schedule dependent. Dose densification of paclitaxel given weekly over 6 weeks on
      a split-dose schedule for an overall increase in dose intensity was thought to
      improve the therapeutic index of paclitaxel in a variety of advanced malignancies
      and to be suitable for outpatient administration. For this study, chemotherapy
      consisted of a weekly 1-hour infusion of paclitaxel at a starting dose of 40
      mg/m2/wk for 6 weeks, followed by a 2- to 3-week interval. Paclitaxel dosage was
      escalated in 10 mg/m2/wk increments in subsequent patients, to a maximum dosage
      of 90 mg/m2/wk. Intravenous dexamethasone, cimetidine, clemastine, and
      ondansetron were administered immediately before the paclitaxel infusion. Fifty
      patients participated in the study. The male to female ratio was 21 to 29, the
      median age was 53.2 years (age range, 33 to 74), and the median performance
      status was 1. All patients were chemotherapeutically pretreated. Overall response
      included five complete responses (10%), 15 partial responses (30%), 19 no change
      (38%), and 11 disease progressions (22%). Median dose intensity was 410 mg/m2/6
      wk (range, 200 to 540 mg/m2/6 wk). Hematologic toxicity was mild, with no grade 3
      or 4 toxicity up to 90 mg/m2/wk. No hypersensitivity reactions or neurologic or
      cardiac toxicities were documented. Dose-densified, weekly paclitaxel is
      concluded to be active in a variety of pretreated tumor entities. The overall low
      hematologic and peripheral toxicity profile suggests that further dose
      intensification of weekly paclitaxel and/or combination with other cytotoxic
      agents (eg, cisplatin/carboplatin, ifosfamide, etoposide) may be warranted.
      Paclitaxel can be given safely in the outpatient setting. Paclitaxel 90 mg/m2/wk
      is recommended for single-agent treatment. Dose-densified paclitaxel may be
      considered a valuable and promising alternative to standard 3-week treatment,
      with further options possible in combination chemotherapy.

PMID- 9007119
TI  - Combination paclitaxel (1-hour) and carboplatin (AUC 7.5) in advanced non-small
      cell lung cancer: a phase II study by the Fox Chase Cancer Center Network.
AB  - We have previously reported a 62% response rate and 54% 1-year survival rate for
      patients with advanced non-small cell lung cancer (NSCLC) treated with paclitaxel
      (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion in
      combination with carboplatin, using area under the concentration-time curve
      dosing (FCCC 93-024). Myelosuppression proved dose limiting, but was
      substantially reduced by the routine use of granulocyte colony-stimulating factor
      during the second and subsequent cycles. Antitumor activity has been reported
      with minimal myelosuppression, with paclitaxel 135 and 200 mg/m2 given every 3
      weeks by 1-hour infusion to patients with NSCLC. In November 1994, we initiated a
      phase II trial of paclitaxel 175 mg/m2 given over 1 hour, with carboplatin dosed
      to a fixed, targeted area under the concentration-time curve of 7.5 every 3
      weeks. In the absence of grade 4 myelosuppression, paclitaxel was escalated on an
      intrapatient basis by 35 mg/m2 per cycle to a maximum dose of 280 mg/m2 by cycle
      4. Granulocyte colony-stimulating factor was not routinely used. Eligibility
      stipulated advanced, measurable, chemotherapy-naive NSCLC. Of 47 patients
      accrued, 39 (83%) had Eastern Cooperative Oncology Group performance status 1.
      The median age was 64 years; 40 patients were evaluable for toxicity. Of the
      first 20 evaluable patients accrued (cohort A), myelosuppression was tolerable.
      Cumulative peripheral sensory neuropathy grade > or = 1 in 15 (75%) patients and
      grade 3 in six (30%), however, generally occurring at paclitaxel doses greater
      than 215 mg/m2, obligated removal from study of at least three patients, despite
      the absence of disease progression, and proved to be dose-limiting. Consequently,
      the protocol was revised: the starting dose of paclitaxel was reduced to 135
      mg/m2, with intrapatient dose escalation of 40 mg/m2 per cycle to a maximum dose
      of 215 mg/m2, thus recapitulating the original dosing schema used in FCCC 93-024.
      To date, 25 patients have been enrolled in this second cohort (cohort B) and
      treatment has been better tolerated. Of 21 evaluable patients, 13 (62%) have
      experienced peripheral sensory neuropathy, but only one (5%) has been grade 3.
      Myelosuppression also has been less pronounced, with 33% grade 4 granulocytopenia
      and 13% grade > or = 3 thrombocytopenia in cohort B compared with 70% and 50%,
      respectively, in cohort A. Of the first 22 patients accrued to cohort A, 12 (55%)
      had major objective responses. Median event-free survival is 23 weeks and median
      survival is 47 weeks. Of 15 evaluable patients in cohort B, five (33%) have had
      major objective responses. It is too early to report survival data. In
      conclusion, paclitaxel by 1-hour infusion in combination with carboplatin at a
      fixed targeted area under the concentration-time curve of 7.5 is an active
      regimen in advanced NSCLC. Neurotoxicity, rather than myelosuppression, is dose
      and protocol limiting at paclitaxel doses exceeding 215 mg/m2.

PMID- 9007120
TI  - Paclitaxel plus carboplatin in the treatment of patients with advanced lung
      cancer: a Vanderbilt University Cancer Center phase II trial (LUN-46).
AB  - In studies conducted by the Eastern Cooperative Oncology Group, treatment with
      either paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) or
      carboplatin was associated with an improvement in 1-year survival in patients
      with stage IV non-small cell lung cancer (NSCLC). Based on these findings, a
      phase II trial of carboplatin plus paclitaxel was conducted in patients with
      advanced NSCLC to determine the activity and toxicity of this regimen.
      Eligibility requirements included stage IIIB or IV histologically confirmed
      NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, no prior
      chemotherapy, and adequate hematologic, renal, hepatic, and cardiac functions.
      Paclitaxel was administered intravenously over 24 hours at a dose of 135 mg/m2
      (28 patients) or 175 mg/m2 (23 patients), followed by a 1-hour infusion of
      carboplatin on day 2. Carboplatin was administered at a dose of 300 mg/m2 (16
      patients) or, using the Calvert formula, a dose calculated to achieve an area
      under the concentration-time curve of 6 mg/mL x min (35 patients). Treatment was
      repeated every 28 days for a total of six cycles. Among the 51 eligible patients,
      34 were men and 17 were women; their median age was 60 years and their median
      Eastern Cooperative Oncology Group performance status was 1. Six patients had
      stage IIIB and 45 had stage IV disease. Grade 3 or 4 granulocytopenia and
      thrombocytopenia were observed in 47% and 3% of treatment cycles, respectively.
      The most common nonhematologic toxicities noted included nausea and emesis,
      neuropathy, and arthralgia and myalgia. There were no complete responses and 14
      partial responses, for an overall response rate of 27% (95% confidence interval,
      17% to 41%). Median survival was 38 weeks and the survival rate at 1 year was
      32%. Paclitaxel plus carboplatin, as given in this study, was found to be a
      moderately active regimen in patients with advanced NSCLC. This regimen warrants
      comparison with existing cisplatin-based regimens in a prospective randomized
      trial.

PMID- 9007122
TI  - Preliminary results of a phase I/II clinical trial of paclitaxel and carboplatin
      in non-small cell lung cancer.
AB  - Forty-nine patients with non-small cell lung cancer were treated in a study
      designed to establish the maximum tolerated dose of outpatient paclitaxel (Taxol;
      Bristol-Myers Squibb Company, Princeton, NJ), given by 3-hour infusion, combined
      with a fixed dose of carboplatin (area under the concentration-time curve [AUC] =
      6, Calvert method). The study population included 31 men and 18 women with
      previously untreated, unresectable stage III or IV non-small cell lung cancer.
      Patients had a median age of 62 years (age range, 46 to 81 years) and a median
      Southwest Oncology Group performance status of 1 (range, 0 to 2). With six to 10
      patients treated at each dose level, paclitaxel was given at a starting dose of
      150 mg/m2, and doses were escalated by 25-mg/m2 increments. The carboplatin dose
      was fixed at an AUC of 6. Paclitaxel 250 mg/m2 was established as the maximum
      tolerated dose of this combination, and severe (grade 3) sensory neuropathy was
      defined as the dose-limiting toxicity. Objective responses were documented in 26
      of 42 patients with objectively measurable disease, for an overall response rate
      of 62%. Although these data are preliminary, this regimen appears to be
      efficacious and cost-effective, and warrants further study. Paclitaxel 225 mg/m2
      combined with carboplatin (AUC = 6) every 3 weeks is recommended for follow-up
      phase II and III clinical trials.

PMID- 9007121
TI  - Phase II study of paclitaxel and cisplatin in patients with non-small cell lung
      cancer.
AB  - Few cytotoxic agents tested in adequate phase II trials involving patients with
      non-small cell lung cancer have produced single-agent response rates greater than
      15%. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of
      them, with reported response rates ranging from 21% to 36%. Platinum-based
      regimens have been key to the development of the most effective combination
      therapies for NSCLC. We are currently investigating the efficacy and toxicity of
      combining paclitaxel (175 mg/m2) given by 3-hour infusion, followed by cisplatin
      (75 mg/m2) via 1-hour infusion, on a 21-day schedule for the treatment of 75
      chemotherapy-naive patients with stage IIIB (17.3%) or stage IV (82.6%) non-small
      cell lung cancer. Patient characteristics include a median age of 58 years (age
      range, 28 to 75 years) and a median Eastern Cooperative Oncology Group
      performance status of 2; 19 patients (25.3%) are women and 56 (74.7%) are men.
      All patients received standard prophylactic premedication as well as adequate
      hydration. To date, 75 subjects and 328 courses are evaluable for toxicity.
      Hematologic toxicities have been moderate; grade 3 or 4 neutropenia occurred in
      37% of cycles (50% of patients), and grade 3 or 4 thrombocytopenia was observed
      in only 2% of cycles (2% of patients). Other notable toxicities were World Health
      Organization grade 2 or 3 alopecia and nausea/vomiting. Grade 1 or 2 peripheral
      neuropathy occurred in 26% and grade 3 or 4 in only 1% of all courses. Of 67
      patients evaluable for response, complete remission was noted in three (5%)
      patients, partial remission in 25 (37%) patients, stable disease in 22 (33%)
      patients, and progressive disease in 17 (25%) patients. These results suggest
      that combination paclitaxel/cisplatin is active and well tolerated in the
      treatment of non-small cell lung cancer.

PMID- 9007124
TI  - Paclitaxel and carboplatin as neoadjuvant chemotherapy in operable (stage I and
      II) and locally advanced (stage IIIA-N2) non-small cell lung cancer.
AB  - In 1995, a randomized intergroup study of neoadjuvant chemotherapy followed by
      either surgery or radiotherapy in the treatment of non-small cell lung cancer was
      started under the auspices of the European Organization for Research and
      Treatment of Cancer (EORTC 08941). The objective of this study is to investigate
      whether surgery or radiotherapy represents superior locoregional treatment, in
      terms of survival and quality of life, for patients with stage IIIA(N2) non-small
      cell lung cancer who have achieved a response after three courses of neoadjuvant
      chemotherapy. A phase II side study will investigate the clinical and pathologic
      response rate (if applicable), as well as acute and late side effects during or
      after consecutive surgery and/or radiotherapy of combination paclitaxel (Taxol;
      Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin. It is planned that
      paclitaxel 175 mg/m2 will be given as a 3-hour infusion, followed by a 30-minute
      infusion of carboplatin at a dose based on a target area under the concentration
      time curve of 6 mg x min/mL. This phase II study was started in October 1996.
      Depending on the response rate and early and late side effects observed in this
      well-defined, prognostically favorable group of patients, it will be decided
      whether and how to use the same combination chemotherapy in an ongoing randomized
      trial currently being conducted by the Dutch Lung Cancer Study Group (DLCSG 94
      2). In the latter trial, patients with stage I and II non-small cell lung cancer
      are randomized to immediate surgery or two courses of neoadjuvant chemotherapy.
      Responding patients will receive another two courses of chemotherapy before
      surgery; nonresponders will go directly to surgery.

PMID- 9007123
TI  - Phase I/II trial of weekly paclitaxel in patients with advanced lung cancer.
AB  - During previous phase I experience of weekly paclitaxel (Taxol; Bristol-Myers
      Squibb Company, Princeton, NJ) used as a radiation sensitizer, decreased
      hematologic toxicity was noted. Therefore, an extended phase I/II trial of weekly
      paclitaxel in patients with chemotherapy-naive, metastatic non-small cell lung
      cancer was conducted to determine the maximum tolerated dose and activity of this
      alternative schedule. Twenty-six patients entered this study through six dose
      levels of paclitaxel (100, 125, 135, 150, 175, and 200 mg/m2/wk) administered
      weekly for 6 of 8 weeks. Doses were escalated if more than 80% of the intended
      dose was administered in the preceding cohort without evidence of grade 3
      nonhematologic toxicity. All patients had a performance status of 0 to 2 and a
      median age of 63 years. Sites of disease included the lung, bone, liver, soft
      tissue, and brain. Twenty-four patients completed the first 8-week cycle and are
      evaluable for toxicity and response. Dose-limiting toxicity occurred at 200
      mg/m2/wk and consisted primarily of neutropenia. Only one evaluable patient
      required hospitalization for febrile neutropenia. Other toxicities included rash,
      pulmonary infiltrate, myalgia, neuropathy, and alopecia. Nine of 24 patients
      (38%) demonstrated objective responses. We conclude that the maximum tolerated
      dose of weekly paclitaxel administered for 6 weeks in an 8-week cycle is 175
      mg/m2/wk. The response rate is encouraging and this schedule merits further
      investigation.

PMID- 9007125
TI  - Preoperative paclitaxel plus carboplatin for patients with intermediate-risk non
      small cell lung cancer.
AB  - A multi-institutional phase II trial of paclitaxel (Taxol; Bristol-Myers Squibb
      Company, Princeton, NJ) 225 mg/m2 over 3 hours and carboplatin dosed to an area
      under the concentration-time curve of 6 by the Calvert formula given
      preoperatively every 3 weeks for two cycles in patients with intermediate-risk
      non-small cell lung cancer is described. Patients must be surgical candidates
      with T2N0, T1-2N1, or T3N0 disease determined by a combination of surgical
      (mediastinum) and clinical (hilum) staging. The outcome for patients in this
      intermediate-risk group is significantly worse than that for T1N0 patients, but
      is good enough to warrant their routine consideration as surgical candidates. The
      conceptual framework of the study is based on a limited amount of animal data,
      the suggestion of benefit in several other diseases, and recent results of trials
      of preoperative therapy for patients with stage IIIA non-small cell lung cancer
      who also appear to demonstrate clinical benefit.

PMID- 9007126
TI  - Paclitaxel and carboplatin in inoperable non-small cell lung cancer.
AB  - Based on the activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb
      Company, Princeton, NJ) and the significant 1-year survival rates of patients
      with non-small cell lung cancer treated with carboplatin, the Hellenic
      Cooperative Oncology Group initiated a phase II trial using both agents in
      patients with inoperable stage III or IV disease to investigate the efficacy and
      toxicity of the combination. Since July 1995, 31 patients fulfilling all
      eligibility criteria entered this study. All patients received paclitaxel 175
      mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the
      concentration-time curve of 7, every 3 weeks. No granulocyte colony-stimulating
      factor was given. Among the 29 male and two female patients, the median age was
      55 years (age range, 29 to 73 years) and the median Eastern Cooperative Oncology
      Group performance status was 1. Most of the patients had stage IV adenocarcinoma
      (19) with low differentiation (15). The median number of chemotherapy cycles was
      two, with a range of one to six. Among 21 patients evaluable, seven achieved a
      partial response, 10 had stable disease, and four had progressive disease. It is
      too early to evaluate nine patients. Grade 2/3 nonhematologic toxicity included
      alopecia (48%), neurotoxicity (3.7%), and myalgia/arthralgia (7.4%). Grade 2/3
      neutropenia occurred in 11.1% of patients, whereas grade 2 thrombocytopenia was
      seen in only 3.7%. One patient died following complications of severe allergic
      reaction. In conclusion, although this study is ongoing, combination treatment
      using paclitaxel and carboplatin is both effective and well tolerated in patients
      with inoperable non-small cell lung cancer.

PMID- 9007127
TI  - Chemotherapy in the management of patients with inoperable non-small cell lung
      cancer.
AB  - Lung cancer remains a major epidemic problem worldwide. The majority of cases are
      associated with cigarette smoking and the number of people who smoke continues to
      increase. As a result, the number of lung cancer cases and deaths is expected to
      increase proportionately over the next decade. The majority of patients who
      develop lung cancer die of this disease. Non-small cell lung cancer (NSCLC)
      accounts for 75% of all new cases. The only hope for significant survival depends
      on surgical resection. At the time of initial presentation, unfortunately, the
      vast majority of patients are inoperable, either because of advanced disease or
      because of the presence of comorbid medical conditions such as coronary artery
      disease. For these reasons, the overall survival rates for patients with NSCLC
      range from 10% to 15%, figures that have not improved substantially for 20 years.
      The role of systemic chemotherapy in this population remains debatable for many
      physicians. Nevertheless, recent studies clearly demonstrate that effective
      systemic chemotherapy in selected patients can improve survival, quality of life,
      and performance status. Recently, newer cytotoxic agents, such as vinorelbine,
      gemcitabine, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ),
      docetaxel, and the camptothecins, have demonstrated their activity in treating
      patients with NSCLC. When combined with other effective agents, response rates
      exceeding 50% have been achieved, with median survivals of more than 1 year. The
      use of these newer agents in combination with well-established agents holds
      promise for the role of systemic chemotherapy in the future management of
      patients with early or late-stage NSCLC.

PMID- 9007128
TI  - Paclitaxel and carboplatin: a phase I study in advanced non-small cell lung
      cancer.
AB  - In the treatment of non-small cell lung cancer paclitaxel (Taxol; Bristol-Myers
      Squibb Company, Princeton, NJ) has significant activity and carboplatin has
      single-agent activity comparable with that of cisplatin, with less pronounced
      nonhematologic toxicity. The optimal doses of paclitaxel and carboplatin in
      combination have not been determined. We designed a phase I study combining a
      fixed paclitaxel dose of 175 mg/m2, administered either by 3- or 1-hour infusion,
      with escalating doses of carboplatin given every 4 weeks. The starting
      carboplatin dose was 175 mg/m2, with planned dose increases in increments of 25
      mg/m2. The primary study objective was to find the maximum tolerated dose of the
      combination. Secondary objectives were to determine the toxicity profile,
      response rate, and feasibility of a 1-hour paclitaxel infusion with steroid
      premedication delivered only 1 hour before the paclitaxel infusion. Eligibility
      criteria included age 18 to 75 years, no prior chemotherapy, stage IIIB to IV
      disease, Eastern Cooperative Oncology Group performance status 0 to 2, no second
      tumors, measurable or evaluable disease, and informed consent. We achieved a
      carboplatin dose level of 300 mg/m2 without reaching the maximum tolerated dose.
      The dose-limiting toxicity was granulocytopenia. However, only one patient had a
      neutrophil count less than 500/microL during the first cycle. Other toxicities
      during the first and remaining 73 delivered cycles were mild to moderate. Only
      one patient had treatment delayed, and no dose reductions were necessary. Of 22
      patients entered, 19 were evaluable for response (two were not evaluable and one
      was too early to evaluate). Six partial responses (31%; 95% confidence interval,
      13% to 57%), five (26%) stable diseases, and eight (42%) disease progressions
      were observed. No additional side effects were observed with the 1-hour
      paclitaxel infusion and single-dose steroid premedication 1 hour before
      chemotherapy. The study will continue until the paclitaxel/carboplatin maximum
      tolerated dose is reached.

PMID- 9007129
TI  - Preliminary results of a dose-finding study of paclitaxel and carboplatin in
      patients with advanced non-small cell lung cancer.
AB  - This ongoing phase I study sought to establish the maximum tolerated dose of the
      combination of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company,
      Princeton, NJ) given without routine growth factor support to previously
      untreated patients with stage IIIB and IV non-small cell lung cancer. Paclitaxel
      was administered as a 3-hour intravenous infusion. The carboplatin infusion was
      administered over 30 minutes immediately afterward. Patients were assigned
      sequentially to one of eight treatment groups in which paclitaxel and carboplatin
      were administered in doses ranging from 130 to 185 mg/m2 and from 230 to 350
      mg/m2, respectively. Twenty-four patients have been treated to date, and the
      maximum tolerated dose has been reached at paclitaxel 185 mg/m2 and carboplatin
      350 mg/m2. The combination has an excellent safety profile, with only a few,
      short-lasting episodes of neutropenia observed and no evidence of infection. At
      the doses tested, thrombocytopenia has not occurred.

PMID- 9007130
TI  - Phase I dose-escalation trial of paclitaxel and ifosfamide in patients with
      advanced non-small cell lung cancer.
AB  - This phase I dose-escalation study was undertaken to determine the maximum
      tolerated doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton,
      NJ) and ifosfamide that could be administered without growth factors to
      previously untreated patients with non-small cell lung cancer. Forty patients
      with advanced non-small cell lung cancer were treated with a 3-hour infusion of
      paclitaxel and a 1-hour infusion of ifosfamide, repeated every 3 weeks. Groups of
      three patients each entered at escalating dose levels in a traditional phase I
      design. Starting doses were paclitaxel 100 mg/m2 and ifosfamide 3 g/m2; all
      patients received premedication with dexamethasone and diphenhydramine, and some
      also received a 5-HT3 blocker. Dose escalation was permitted only after full
      toxicity assessment had been completed for two cycles for all patients at a dose
      level. Dose escalation of paclitaxel continued to 225 mg/m2 without dose-limiting
      toxicity, but further escalation was not attempted because of the known
      likelihood of neurotoxicity above this dosage. Instead, ifosfamide was increased
      to 4 g/m2 for the final dose level. At these doses, dose-limiting
      myelosuppression was not seen, and there was only one episode of febrile
      neutropenia in 162 treatment cycles. Drug-related ifosfamide toxicities included
      gross hematuria and confusion in one patient each; paclitaxel-related symptoms
      included flu-like syndrome in most patients, arthralgia and/or myalgia in eight
      and 25 patients, respectively, and paresthesia in 14 patients. Despite
      premedication, 15 patients experienced grade 1 hypersensitivity reactions.
      Partial response was seen in 21% of patients (confidence interval, 9.3% to
      36.5%), and the median duration of response was 5.9+ months (range, 3 to 14
      months). The median survival was 9.1 months (range, 1 to 12 months). In summary,
      outpatient paclitaxel given over 3 hours and single-dose ifosfamide given over 1
      hour may be combined safely without hematopoietic growth factors for the
      treatment of patients with non-small cell lung cancer. The recommended doses for
      phase II study are paclitaxel 225 mg/m2 and ifosfamide 4 g/m2, every 3 weeks.

PMID- 9007131
TI  - Paclitaxel via 1-hour infusion: clinical experience.
AB  - In phase II trials, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton,
      NJ) can be safely administered via a 1-hour infusion. One-hour infusions of
      paclitaxel also have been administered safely in combination with many other
      cytotoxic regimens, including cisplatin/etoposide/radiation,
      carboplatin/etoposide (with or without radiation), mitoxantrone/5
      fluorouracil/leucovorin, carboplatin, and carboplatin/5-fluorouracil. Notable
      activity has been seen in patients with several neoplasms, including stages
      III/IV non-small cell lung cancer, small cell lung cancer, advanced breast
      cancer, carcinoma of unknown primary site, urothelial carcinomas, and other
      advanced squamous cell carcinomas. Further study will determine whether these or
      similar combinations represent improved therapeutic alternatives.

PMID- 9007132
TI  - Single-agent paclitaxel as a 3-hour infusion.
AB  - This ongoing phase II trial of patients with inoperable stage IIIB-IV non-small
      cell lung cancer is seeking to determine the efficacy and toxicity of paclitaxel
      (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when administered as a 3
      hour infusion. The 58 patients now evaluable met standard eligibility
      requirements, including no prior chemotherapy. Paclitaxel 225 mg/m2 was delivered
      every 3 weeks for up to 10 courses, depending on patient response. All patients
      were evaluable for toxicity and 50 were evaluable for response. There were no
      complete responses, 12 patients had partial responses, 12 had progressive
      disease, and 26 had no change. The median time to response was 8.7 weeks; the
      median survival was 10 months. Leukopenia, when observed, was grade 1 or 2 in all
      but one case. Likewise, all nonhematologic effects were mild, with the exception
      of one case of grade 3 gastrointestinal toxicity. The 3-hour infusion schedule is
      more convenient, and the authors feel that the safety of the schedule is
      confirmed by these results. However, the efficacy of the shortened schedule,
      compared with a 24-hour infusion, remains to be proven.

PMID- 9007133
TI  - One-hour paclitaxel in the treatment of non-small cell lung cancer.
AB  - This review describes studies with two paclitaxel (Taxol; Bristol-Myers Squibb
      Company, Princeton, NJ)-containing treatments for non-small cell lung cancer
      (NSCLC). In an ongoing study, 100 patients with previously untreated stage IIIB
      or IV NSCLC received combination therapy comprised of paclitaxel 225 mg/m2 via 1
      hour infusion and carboplatin, dosed to an area under the concentration-time
      curve of 6.0. Both drugs were given intravenously and cycles were repeated every
      21 days. Patients with objective responses or stable disease after two courses
      continued for a maximum of 10 treatment courses. Of the 100 patients, 36% had an
      objective response, including three complete responses. An additional 33% had
      stable disease/minor response. The regimen was well tolerated. Grade 3/4
      peripheral neuropathy, which usually appeared during or after the fourth
      treatment course, was noted in 18% of patients. An earlier study evaluated
      combined-modality therapy in 33 patients with unresectable stage IIIA or IIIB
      NSCLC. Two courses of intravenous induction chemotherapy were initially
      administered (paclitaxel 135 mg/m2 via 1-hour infusion, day 1; cisplatin 60
      mg/m2, day 2; and etoposide 100 mg/m2, days 1 to 3). After two courses, radiation
      therapy was initiated at 1.8 to 2.0 Gy daily (median total dose, 60 Gy). Patients
      also received chemotherapy concurrent with radiation: paclitaxel 135 mg/m2 over 1
      hour on day 1, cisplatin 5 mg/m2 days 2 to 5 and 8 to 12, and etoposide 25 mg/m2
      days 1 to 5 and 8 to 12. Cycles were repeated every 21 days. Of the 29 patients
      who completed therapy, 41% achieved complete responses and 41% had partial
      responses. Median survival exceeds 14 months, and 30% of patients continue
      progression free 12 to 29 months after completion of therapy. Grade 3/4
      esophagitis was observed in 51% of participants and usually occurred during the
      final 2 weeks of combined-modality therapy. The combination of paclitaxel and
      carboplatin is active and well tolerated in patients with advanced NSCLC, and
      paclitaxel-based combined-modality therapy produced a high rate of complete and
      partial responses and encouraging survival data. Continued investigation and
      refinement of these regimens is ongoing.

PMID- 9007134
TI  - Escalating paclitaxel doses combined with carboplatin/etoposide and thoracic
      radiotherapy as preoperative or definitive treatment for stage III non-small cell
      lung cancer.
AB  - We have evaluated escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb
      Company, Princeton, NJ) in combination with carboplatin, cisplatin, etoposide,
      and concurrent thoracic radiotherapy in patients with stage III non-small cell
      lung cancer. Dose-limiting toxicity was observed at paclitaxel 90 mg/m2.
      Subsequent modifications resulted in a new regimen, which consists of a 3-hour
      paclitaxel infusion on day 1 (three dose levels: 80, 100, and 120 mg/m2),
      etoposide 40 mg/m2 intravenously over 1 hour daily on days 2 to 5, and
      carboplatin given at an area under the concentration-time curve of 4 mg/mL x min
      on day 1 after paclitaxel. Treatment courses were repeated every 28 days. Eleven
      patients considered eligible for surgery received two courses. Nonsurgical
      patients (five) received three courses. No episodes of grade > or = 3 nausea and
      vomiting, dermatitis, anorexia, esophagitis, or thrombocytopenia were observed.
      The dose-limiting toxicity (grade 4 granulocytopenia) occurred in three of five
      patients at 120 mg/m2 paclitaxel (level 3). Grade 3 radiation pneumonitis was
      observed in three patients. Nine patients have undergone pulmonary resection:
      four pneumonectomies, four lobectomies, and one segmental resection. No operative
      deaths, respiratory insufficiency, or cardiovascular complications were observed.
      Clinical partial remissions have been observed in 11 of 16 patients overall, and
      two histologic complete remissions were achieved in nine surgical patients. Our
      preliminary results show that pulmonary resection is feasible following treatment
      with radiation and concurrent paclitaxel-containing chemotherapy. Although the
      maximum tolerated paclitaxel dose in the present study was relatively low,
      favorable initial responses warrant further study of paclitaxel-containing
      combination chemotherapy and concurrent radiation. We next plan to delete
      etoposide from our chemoradiotherapy regimen and escalate the paclitaxel dose.

PMID- 9007135
TI  - Paclitaxel and simultaneous radiation in the treatment of stage IIIA/B non-small
      cell lung cancer.
AB  - In a clinical phase II trial, escalating doses of paclitaxel (Taxol; Bristol
      Myers Squibb Company, Princeton, NJ) were given with concurrent radiation to
      patients with stage IIIA/B non-small cell lung cancer. Radiotherapy was given in
      daily doses of 2 Gy, 5 days a week, in weeks 1 through 3 and 6 through 8.
      Paclitaxel was given on day 1 of weeks 1 through 3 and 6 through 8, at a starting
      dose level of 50 mg/m2. Subsequent paclitaxel dose levels were 60, 72, 86, and
      103 mg/m2. Three to six patients were included at each dose level until
      intolerable toxicity (World Health Organization grade 3 or 4 leukopenia) occurred
      in three of six patients. To date, 27 patients have entered the protocol.
      Hematologic toxicity was mild with no severe myelosuppression up to the 86-mg/m2
      dose level. At paclitaxel 103 mg/m2, four of six patients developed grade 3 or 4
      leukopenia, and dose escalation was stopped. The maximum tolerated dose was thus
      determined to be 86 mg/m2. The main clinical toxicity was the occurrence of
      pulmonary infections (seven patients), one of whom had Pneumocystis carinii
      infection; the six others had interstitial infections with no pathogen isolated.
      Mild to moderate esophagitis was seen in five patients. Thus far, of 24 patients
      evaluable for response, 18 showed decreased tumor size. Four patients achieved
      major responses (near-complete disappearance of radiologic tumor signs), 11
      patients achieved partial remission, and three patients had a minor response. The
      overall response rate was 75%. In summary, the maximum tolerated dose of
      paclitaxel in this study has been determined to be 86 mg/m2 weekly. Pulmonary
      infections represent the major clinical toxicity, and the high response rate
      merits further clinical evaluation of this regimen.

PMID- 9007136
TI  - Chemoradiotherapy in non-small cell lung cancer:
      paclitaxel/carboplatin/radiotherapy in regionally advanced disease.
AB  - Based on superior results observed with combined-modality therapy over
      radiotherapy alone and on the authors' previous work with carboplatin and
      standard daily thoracic radiotherapy in patients with advanced, unresectable non
      small cell lung cancer, a phase II study was designed to incorporate
      radiosensitizing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company,
      Princeton, NJ) into the carboplatin/radiotherapy regimen, to improve the
      therapeutic index and define the toxicities. Thirty-two patients have been
      entered. Paclitaxel 45 mg/m2/wk was administered over 3 hours prior to
      carboplatin (100 mg/m2/wk) and thoracic radiotherapy (1.8 Gy/d 5 days a week;
      total dose, 60 to 65 Gy). No grade 4 toxicities occurred. Seven patients had
      chemotherapy doses delayed because of grade 3 neutropenia, and one patient had
      grade 3 mucositis/esophagitis that required hospitalization. Median survival has
      not yet been reached, and all patients are being followed. These preliminary data
      demonstrate the feasibility of combined concurrent chemoradiotherapy, with
      acceptable toxicities. Further investigation is needed to optimize carboplatin
      dosage with adaptive control using formulas based on pharmacokinetics and
      pharmacodynamics. Full-dose induction chemotherapy regimens to maximize the
      systemic effects of chemotherapy should precede concurrent chemoradiotherapy in
      future studies.

PMID- 9007137
TI  - Paclitaxel plus carboplatin and concurrent radiation therapy for patients with
      locally advanced non-small cell lung cancer.
AB  - Previously untreated patients with stages IIIA or IIIB non-small cell lung cancer
      entered this phase II study to evaluate the activity and toxicity of combined
      paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin
      and concurrent radiation. Patients received paclitaxel 50 mg/m2/wk as a 1-hour
      infusion and carboplatin area under the concentration-time curve of 2/wk for 7
      weeks with radiation to the primary tumor and regional lymph nodes (44 Gy)
      followed by a boost to the tumor (22 Gy). In addition, patients received two
      additional cycles of paclitaxel 200 mg/m2 and carboplatin (area under the
      concentration-time curve of 6) 3 weeks apart. From March 1995 to February 1996,
      23 patients entered the study and their overall response rate (complete plus
      partial responses) was 82%. The major toxicity was esophagitis. Nine patients
      (45%) had experienced grades 3 or 4 esophagitis by the end of the 7-week
      concurrent phase. Seven of the nine patients recovered from the esophagitis
      within 2 weeks and received the additional two cycles of paclitaxel 200 mg/m2 and
      carboplatin (area under the concentration-time curve of 6). Only one patient (4%)
      had grade 4 pneumonitis; this patient also recovered within 2 weeks and received
      the final two doses of combined chemotherapy. Therapy with paclitaxel,
      carboplatin, and concurrent radiation is a promising treatment for patients with
      locally advanced non-small cell lung cancer; it has a high response rate and
      acceptable toxicity.

PMID- 9007138
TI  - Paclitaxel and simultaneous radiation in locally advanced stage IIIA/B non-small
      cell lung cancer: a clinical phase I study.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the
      most active single agents for the treatment of non-small cell lung cancer, with
      response rates of 21% to 24%. We present a phase I study with paclitaxel and
      simultaneous radiation in previously untreated, locally advanced, inoperable,
      stage IIIA/B non-small cell lung cancer. The aims of the study were to determine
      the maximum tolerated dose, define the safety and toxicity, and obtain
      preliminary data about the activity of the combined modality. Patients received a
      fixed dose of radiotherapy (1.8 Gy/d, 5 days a week for 6.5 weeks, for a total
      dose of 59.4 Gy) and concomitant chemotherapy with paclitaxel 45 mg/m2 days 1, 8,
      and 15 in level 1; days 1, 8, 15, 22, and 29 in level 2; and days 1, 8, 15, 22,
      29, 36, and 43 in level 3. The paclitaxel dosage was increased to 55 mg/m2 on
      days 1, 8, 15, 22, 29, 36, and 43 in level 4. Paclitaxel was administered as a 3
      hour continuous intravenous infusion. Dexamethasone, clemastine, and ranitidine
      were given for hypersensitivity prophylaxis. Twenty-two patients (18 men and four
      women) entered the study; their median age was 66.5 years (age range, 38 to 74
      years). Disease stage was IIIA in six of 22 patients and stage IIIB in 16. Six
      patients were treated at level 1, five at level 2, five at level 3, and six at
      level 4. There were 18 patients evaluable for toxicity and response. Side effects
      generally were moderate during the treatment period. One patient withdrew by
      request after the first course, one patient died of tumor bleeding after five
      courses, one patient died of progressive disease (lymphangiosis carcinomatosa of
      both lungs) after the sixth course, and one patient is too early for evaluation.
      Among the 18 patients evaluable for response, there were one complete and 10
      partial remissions; seven patients reached a minor response. It is concluded that
      the therapy was well tolerated in these patients. Importantly, no severe adverse
      events were observed that could be associated with paclitaxel or radiotherapy.
      This combined modality appears to be a practicable and effective treatment of non
      small cell lung cancer. The maximum tolerated dose has not yet been reached, and
      dose escalation is planned.

PMID- 9007139
TI  - Phase I/II study of paclitaxel and radiotherapy in non-small cell lung cancer.
AB  - To establish the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers
      Squibb Company, Princeton, NJ) as a radiosensitizing agent and to determine its
      optimal therapeutic dose when combined with conventionally fractionated
      radiotherapy in the treatment of non-small cell lung cancer, a phase I/II study
      was undertaken in 16 treatment-naive patients. Beginning at 40 mg/m2/wk with
      doses escalated in 10 mg/m2 increments until dose-limiting toxicity was
      encountered, paclitaxel was administered over 3 hours to successive three-patient
      cohorts. Radiotherapy (2 Gy/d x 5 d/wk; maximum total dose, 50 Gy) was delivered
      after the paclitaxel infusion. Treatment continued for 5 successive weeks. All 16
      patients are evaluable for response and toxicity. Hematologic toxicity was low,
      with red blood cells and platelets remaining stable and leukocyte decreases
      (mean, 60%) attributed to radiotherapy. Nonhematologic toxicity included grade
      2/3 esophagitis and neurologic sequelae. Responses were noted at all paclitaxel
      dose levels, including two complete and five partial responses, but the median
      time to progression was only 5 months. Paclitaxel may be combined safely with
      radiotherapy without major toxicity, and the radiosensitizing effect of
      paclitaxel was evident at all doses.

PMID- 9007140
TI  - Weekly paclitaxel with and without concurrent radiation therapy: toxicity,
      pharmacokinetics, and response.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has shown in
      vitro and clinical activity against non-small cell lung cancer and astrocytic
      brain tumors, tumors traditionally thought of as relatively resistant to
      chemotherapy and radiotherapy. Because of its ability to block dividing cells in
      the G2/M portion of the cell cycle (the most radiosensitive phase of the cell
      cycle), paclitaxel is also a potentially potent radiosensitizer. To exploit these
      and other properties of paclitaxel, we explored a weekly, outpatient
      administration schedule, with and without concurrent radiation therapy, in
      patients with non-small cell lung cancer and astrocytic brain tumors. Our
      experience has shown that weekly outpatient administration is feasible, that
      remarkably high dose intensities can be achieved with acceptable toxicity, and
      that the specific dose-limiting toxicity appears to depend on administration
      schedule, type of concurrent radiotherapy, and certain patient characteristics.
      Preliminary response data are very encouraging. At the same time, pharmacokinetic
      studies have suggested possible reasons for our ability to use such exorbitant
      dose intensities safely, and also have shown that sustained plasma paclitaxel
      levels above the putative radiosensitizing threshold can be achieved continuously
      during a 6-week course of radiotherapy. Specific results, dosing recommendations,
      and plans for future studies are discussed.

PMID- 9007141
TI  - Future directions in therapeutic approaches for small cell lung cancer.

PMID- 9007142
TI  - Benign and malignant eccrine poroma--a flow cytometric comparison.
AB  - Eccrine poroma is a benign, slow growing, solitary adnexal tumor. Malignant
      degeneration may take place in longstanding solitary lesions; in such cases
      cutaneous and fatal visceral metastases have occurred. Our goal was to determine
      whether flow cytometry yields useful diagnostic and prognostic information on
      benign and malignant eccrine poroma. Flow cytometric analysis of the nuclear DNA
      ploidy pattern was performed on four samples of eccrine poroma and five samples
      of malignant eccrine poroma. All the histograms of the eccrine poromas were
      diploid. Two of five specimens (40%) of the eccrine porocarcinoma were aneuploid,
      and the other three (60%) were diploid. The diploid pattern represents another
      expression of the benignancy of eccrine poroma. Since abnormal DNA content is
      often correlated with tumor grade, the aneuploid DNA histogram of 40% of the
      patients with malignant eccrine poroma is not a surprising finding in this
      cytologically malignant neoplasm.

PMID- 9007143
TI  - Inhibition of B16 melanoma cell proliferation and alterations in p21 ras
      expression induced by interceptors of signal transduction pathways.
AB  - Anti-tumor effects of agents known to intervene with signal transduction pathways
      (ras and protein kinase c cascades) were examined in the B16 melanoma cell model.
      The compounds examined included: lovastatin, an inhibitor of HMG-CoA reductase,
      which interferes with membrane localization of p21 ras protein; H-7, a classic
      inhibitor of protein kinase C; and tiazofurin, a GTP depleting agent, that might
      affect the GTP/GDP ratio on p21ras. The three agents were found to inhibit the
      proliferation of B16 melanoma cells. Only tiazofurin, as expected, induced a
      significant decrease in GTP levels. Lovastatin and H-7 altered p21 subcellular
      localization. They reduced membrane expression of p21 ras, while increasing its
      expression in the cytosol. Following tiazofurin treatment a trend towards
      increased membranal p21 was observed. These results suggest that p21 is a target
      for the action of signal transduction inhibitors. However, the relationship
      between growth inhibition and altered p21 expression is not yet clear.

PMID- 9007144
TI  - The effect of estrogen replacement therapy on plasma serotonin and catecholamines
      of postmenopausal women.
AB  - We examined the effect of estrogen replacement therapy (ERT) on plasma serotonin
      (5HT) and norepinephrine (NE) and their correlation with serum estradiol,
      luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in 12
      postmenopausal women. Plasma 5HT and NE, estrogen, progesterone, LH and FSH were
      examined every 4 days for 2 consecutive months (before and during ERT). Serotonin
      values were low (32.29 +/- 38.36 nmol/l) and showed an intrinsic spontaneous
      cyclicity with a nadir every 10-11 days. Plasma NE was similar to that observed
      during the follicular phase of the ovulatory cycle (1,216.8 +/- 503.4 pmol/l) and
      showed no cyclicity. ERT significantly increased mean (+/- SD) serum estrogen
      values (from 95.40 +/- 73.31 to 390.72 +/- 347.17 pmol/l, P = 0.0001),
      significantly decreased serum FSH (from 84.04 +/- 14.97 to 52.97 +/- 20.74
      mIU/ml, P = 0.0001) and LH (from 35.35 +/- 13.82 mIU/ml to 29.69 +/- 16.46
      mIU/ml, P = 0.03). Plasma 5HT levels showed a tendency to rise under the
      influence of ERT, but this increase was not statistically significant. Plasma NE
      decreased significantly from 1,216.8 +/- 503.4 to 994.1 +/- 353.89 pmol/l, P
      <0.05. In conclusion, plasma serotonin in postmenopausal women has a 10-11 day
      cycle and is significantly lower than in the follicular phase of ovulating women.
      Plasma NE shows no cyclicity and is significantly decreased by ERT.

PMID- 9007145
TI  - Inverted papilloma of the nose and paranasal sinuses: a study of 56 cases and
      review of the literature.
AB  - Over a period of 32 years, 56 patients with inverted papilloma of the nasal
      cavity and paranasal sinuses were diagnosed and treated at Beilinson Medical
      Center, Israel. Four patients (7%) had an associated malignancy. Several surgical
      approaches were used: limited intranasal excision in 5 patients with an 80%
      failure rate, a Caldwell-Luc approach in 21 patients with a 48% recurrence rate,
      and lateral rhinotomy with medial maxillectomy in 18 patients with only a 22%
      failure rate; a selected group of 9 patients underwent an endoscopic procedure,
      with a 22% recurrence rate. Our results and a review of 19 published reports
      suggest that medial maxillectomy via lateral rhinotomy remains the treatment of
      choice for most cases of inverted papilloma. The role of endoscopic excision in
      selected patients is discussed.

PMID- 9007146
TI  - Screening for colonic neoplastic lesions using flexible sigmoidoscopy in
      employees of a nuclear research center and members of collective settlements.
AB  - It has been shown that screening of average risk individuals reduces the
      incidence of colorectal cancer. The most effective method for screening has yet
      to be determined in terms of cost-effectiveness, but approximately two-thirds of
      colorectal neoplastic lesions are within the reach of the flexible sigmoidoscope.
      It has been estimated that a single such examination at the end of the sixth
      decade may reduce the colorectal cancer incidence by 60%. As part of a screening
      program for colon cancer, short colonoscopy was performed on 399 employees of a
      nuclear research center and 228 members of a collective settlement (kibbutz). The
      examinations were carried out on individuals aged > or = 40 years by two
      experienced endoscopists. The splenic flexure or transverse colon was reached in
      95% of the procedures. Neoplastic lesions were found in 24 (6.0%) and 8 (3.5%)
      screenees (not significant) in the Nuclear Research Center and kibbutz
      populations respectively. Polyps <1 cm in diameter were significantly more common
      in the Nuclear Research Center population but larger polyps and cancers were not.
      In 47 Nuclear Research Center screenees with a family history positive in a first
      degree relative, findings increased to 14.9% (P = 0.016). A family history of
      malignancy was found in 33.8% of kibbutz members but in only 11.8% of Nuclear
      Research Center employees. There was no evidence to suggest that working at the
      Nuclear Research Center increased the risk of colonic neoplasms. We conclude that
      flexible sigmoidoscopy is a valuable screening tool, especially for individuals
      with a first-degree relative with cancer. The yield of neoplastic lesions in the
      Israeli Nuclear Research Center and kibbutz populations is similar to that of the
      general population in the western world. Compliance rates are high in well
      defined populations.

PMID- 9007147
TI  - Augmentation of low ovarian response to superovulation before in vitro
      fertilization following priming with contraceptive pills.
AB  - Poor ovarian response to superovulation treatment is observed in a certain group
      of patients, the so-called 'low responders'. Despite the evolution of
      sophisticated controlled ovarian hyperstimulation (COH) regimens prior to the in
      vitro fertilization (IVF), the ideal stimulation protocol for the low responder
      has yet to be formulated. The objective of this study was to assess the effect of
      oral contraceptive pills (OCP), administered before the initiation of
      superovulation, on ovarian response and IVF treatment results in patients with
      previous 'low response' to exogenous gonadotropin stimulation. The study group
      comprised 42 patients who had exhibited poor ovarian response to standard
      superovulation protocols in at least two previous consecutive treatment attempts.
      Contraceptive pills were administered for 28-42 days and were immediately
      followed by menotropin treatment. The study group (n=50 cycles) was compared with
      the control group consisting of previous cycles (n=88) of the same women.
      Significant differences were noted in peak estradiol levels (983 +/- 739 vs. 517
      +/- 249 pg/ml; P <0.01, paired Student's t test) and number of pre-ovulatory
      follicles between the study and the control groups. Thirty-three of the cycles
      (66%) reached the stage of ovum pick-up, compared with 22 (25%) of the previous
      IVF cycles in these women. The mean number of oocytes retrieved was 6.1 +/- 3.0
      and 2.4 +/- 1.3 in the study and control groups, respectively (P <0.01; paired
      Student's t test). Embryo transfer (ET) was performed in 62% of the treatment
      cycles and resulted in five clinical pregnancies (16.1% per ET). No pregnancies
      were recorded in the control group. This study demonstrates the beneficial effect
      of OCP given prior to IVF treatment, and provides an efficient treatment modality
      for women who consistently respond poorly to standard COH protocols.

PMID- 9007148
TI  - The management of dermoid cysts--a comparative study of laparoscopy and
      laparotomy.
AB  - The aim of our study was to compare laparoscopy with laparotomy for the removal
      of ovarian dermoid cysts. Thirty-eight women with benign ovarian dermoid cyst
      were allocated for either laparoscopy (18 patients) or laparotomy (20 patients).
      The two groups were compared for operative and hospitalization times and
      postoperative course. Operating time was longer (93.6 +/- 23.8 min) and
      hospitalization time significantly shorter (22.4 +/- 6.6 h) in the laparoscopy
      group. No complications were reported in either group. We conclude that operative
      laparoscopy is a safe procedure for the removal of dermoid ovarian cysts and is
      as effective as laparotomy.

PMID- 9007149
TI  - The immune system in severe ovarian hyperstimulation syndrome.
AB  - Recently, evidence has accumulated concerning the interaction between the immune
      and reproductive systems that results from sharing certain lymphohematopoietic
      cytokines and their receptors. Furthermore, several cytokines have been
      implicated as having a role in the prediction and pathophysiology of ovarian
      hyperstimulation syndrome (OHSS). The hitherto known studies concerning the role
      of the immune system in OHSS, together with a hypothesis regarding the role of
      interleukin-2 as a possible culprit of this complication, are presented.

PMID- 9007150
TI  - Pregnancy outcome in renal allograft recipients in Israel.
AB  - The literature contains reports of 2,309 pregnancies in some 1,600 women who have
      undergone renal transplantation. Certain pre-pregnancy factors, especially
      hypertension, renal graft dysfunction and short interval between transplant and
      pregnancy, appear to increase the neonatal risks. We describe the outcome of 42
      pregnancies in 27 allograft recipients at Beilinson Medical Center in Israel
      during the last 8 years. All were treated with combination immunosuppression
      regimens. The average interval from time of transplantation to conception was 3.7
      +/- 0.4 years (2 months to 9 years). Rejection episodes occurred in 37% prior to
      pregnancy but in none during or immediately after pregnancy. Of the 42
      pregnancies 28% ended in therapeutic or spontaneous abortions, and 29 of the 30
      deliveries ended in a life birth. The prematurity rate (65%) was similar to that
      described in the literature. Renal deterioration was evident in seven women (26%)
      within 2 years after delivery. Despite this significant success rate, pregnancy
      in organ transplant patients should still be considered high risk.

PMID- 9007151
TI  - Esterase inhibitors diminish the modulation of gene expression by butyric acid
      derivative, pivaloyloxymethyl butyrate (AN-9).
AB  - Pivaloyloxymethyl butyrate (AN-9) belongs to the family of acyloxyalkyl ester
      prodrugs of carboxylic acids which undergo intracellular hydrolysis to yield
      butyric acid (BA). We have previously shown that AN-9 and BA reduce the level of
      c-myc and enhance c-jun transcripts in HL-60 cells, and that the differentiation
      of these cells, induced by AN-9, is dependent on the presence of intracellular
      esterases. In this study we show that esterase inhibitors abolish the changes
      induced by AN-9 on c-myc and c-jun expression. In contrast, esterase inhibitors
      do not change the effects of BA on c-myc or c-jun. Interestingly, these
      inhibitors affect the modulation induced by both AN-9 and BA on the
      retinoblastoma tumor suppressor gene. These data suggest that AN-9 is indeed a
      prodrug of BA and that prior intracellular hydrolysis by esterases is material
      for AN-9 activity.

PMID- 9007152
TI  - Risk factors associated with the severity of systemic insect sting reactions.
AB  - To evaluate risk factors associated with the severity of systemic insect sting
      reaction and to determine the type of insect responsible for systemic
      anaphylaxis, we conducted a cross-sectional study of 498 patients undergoing
      venom immunotherapy for insect sting reaction in 13 allergy clinics in Israel.
      Data were collected by questionnaire and review of patient records. Eighty
      percent of the patients were treated with honeybee venom, which was used as a
      single therapy in 60% of the group. In a multivariate logistic model the major
      factors identified as significantly influencing the probability of a more severe
      systemic reaction were short time of onset of reaction after stinging (<30 min),
      high number of prior stings (> or = 4), and age (> or = 18 years). A total of
      79.3% of the patients had been stung outdoors, and 50% had lived all their lives
      in rural areas as compared to 10% in the general Israeli population. This study
      reports clinically valuable risk factors for the severity of systemic sting
      reaction. A practical finding was that the honeybee is the insect mostly
      responsible for sting reactions in Israel, but the type of insect is not a
      significant predictor of the severity of the reaction.

PMID- 9007153
TI  - Treatment of experimental inflammatory synovitis with continuous magnetic field.
AB  - The effect of a magnetic field on synovitis in rats was studied. Synovitis was
      induced by bilateral intraarticular injection of zymosan to the hind joints. One
      group of rats was held in a cage with a magnet of 3,800 Gauss on the bottom of
      the cage (treated), while another group was held in a cage without a magnet
      (control). Three weeks following intraarticular zymosan injection all rats were
      killed and the hind joints tissues were examined histologically. The pathologic
      process was noted and graded according to the involvement of various tissue
      components, number of inflammatory foci, and size of the lesion. The histologic
      findings of the tissues from the control group consisted of marked articular
      infiltrate, composed of lymphocytes and plasma cells with some histocytes in 80%
      of the animals. A small articular infiltration of the same nature was observed in
      20% of the treated rats. The inflammatory score was 3.4 +/- 1.1 in the treated
      animals and 6.8 +/- 2.6 in the control group (P = 0.002). These data showed that
      synovitis and the inflammatory process are significantly suppressed by a magnetic
      field.

PMID- 9007154
TI  - Anemia of cancer: pathogenesis and treatment with recombinant erythropoietin.
AB  - The anemia of malignancy is common and is related to several etiologic factors, a
      major one being relative erythropoietin (Epo) deficiency. Blood transfusions, the
      traditional therapy, provides a quick solution but is associated with
      complications. This was the rationale for recombinant human Epo (rHuEpo) in the
      treatment of anemia of cancer. Over the past few years, about 20 publications
      have reported the results of rHuEpo in the treatment of cancer-associated anemia
      in more than 850 patients with a variety of malignancies. In general, more than
      half of the patients responded with a significant increase in their hemoglobin
      level, a decrease in blood transfusion requirements, and an improved performance
      status and quality of life. About 4 weeks are required till the onset of effect.
      The hormone is well tolerated with minimal adverse effects and subcutaneous
      injections appear to be the preferred method of administration. Additional
      studies will hopefully answer several questions including optimal dosage and
      duration of treatment, Epo resistance, and the possibility of predicting the
      response.

PMID- 9007155
TI  - Plasma fibrinogen in Israeli Moslem and Jewish school-children: distribution and
      relation to other cardiovascular risk factors. The Petah Tikva project.
AB  - Plasma fibrinogen levels were measured in 1,175 Israeli schoolchildren, aged 9-18
      years, originating from diverse ethnic groups. The Moslem children displayed
      striking differences in levels and age-patterns of fibrinogen compared to Jewish
      children. Lower mean plasma fibrinogen levels in boys aged 9-10, 13-14 and 16-18
      were observed among Moslem boys, compared to their Jewish counterparts born in
      Israel. Moslem girls showed lower levels of fibrinogen than Jewish Israeli girls
      at ages 9-10 and 16-18. While the Jewish children displayed an age-associated
      fibrinogen pattern comparable at the three age groups, the levels for Moslem
      children increased pre-puberty and decreased post-puberty, peaking at 13-14
      years. No significant difference in mean plasma fibrinogen was found between
      sexes within ethnic groups. A number of statistically significant but low
      correlations (-0.32 to 0.24) were found between plasma fibrinogen and high
      density lipoprotein cholesterol (HDL-C) as a percentage of total cholesterol,
      triglycerides, blood glucose, uric acid, blood pressure, Quetelet index and
      sports activity. The difference between fibrinogen levels might point to a
      possible ethnicity risk factor explanation rather than environmentally acquired
      factors.

PMID- 9007156
TI  - Cardiomyocytes in culture--a model to study the cellular actions of amiodarone.
AB  - The extensive use of amiodarone as an anti-arrhythmic drug is hampered by
      numerous side effects and by insufficient knowledge of its cellular action. The
      use of cell cultures for studying the mechanism of amiodarone action has been
      questioned, since available information has indicated that the doses employed for
      the experiments induce cell damage. We have defined conditions to obtain the
      amiodarone effect on cardiac cells in culture with no detectable damage.
      Amiodarone, 1 microg/ml, a concentration comparable to serum levels of the drug
      in acute and chronically treated humans and rats, reduces cell contractions,
      modifies membrane electrical properties accordingly, increases ATP content, but
      does not alter cell substructure or change enzyme activities. We strongly support
      the use of cell cultures for studying the cellular action(s) of amiodarone and
      offer conditions suitable for such experiments.

PMID- 9007157
TI  - Progression of renal disease--can it be reversed? The role of calcium channel
      blockers and angiotensin-converting enzyme inhibitors.
AB  - The treatment of patients with end-stage renal failure using dialysis has become
      an important factor in the health budgets of the developed countries. Thus,
      prevention of progression of renal disease and a reduction in the number of
      patients requiring dialysis should have a beneficial impact on health budgets.
      This review will examine the effects of calcium channel blockers (CCBs) and
      angiotensin-converting enzyme inhibitors (ACE-Is) on the progression of renal
      disease. Both CCBs and ACE-Is have been shown to slow progression in various
      animal models of various renal diseases. In the human with diabetic and non
      diabetic renal disease, most CCBs have caused a stabilization of renal function
      and in some cases a decrease in proteinuria. ACE-Is have been effective in
      reducing proteinuria and stabilizing renal function in both diabetic and non
      diabetic disease, this effect being independent of the antihypertensive effect.
      There are good theoretical reasons for using a combination of these two classes
      of medications, but there are still insufficient clinical data. In summary, both
      CCBs and ACE-Is may be used to slow the progression of renal disease. ACE-Is seem
      to be preferable, but there may be an advantage to the use of a combination of
      both agents.

PMID- 9007158
TI  - Cirrhotic glomerulonephritis: an underdiagnosed condition.
AB  - Glomerular pathology in liver cirrhosis is common in autopsies but is
      underdiagnosed antemortem. The most common pathologic findings are mesangial
      disease with immunoglobulin A deposits, and membranoproliferative
      glomerulonephritis. The latter is associated, most frequently, with hepatitis C
      infection and cryoglobulinemia. We describe a patient with longstanding liver
      cirrhosis who presented with a nephritic and nephrotic syndrome.
      Membranoproliferative glomerulonephritis was diagnosed on kidney biopsy. There
      was no clinical, laboratory or histologic evidence of hepatitis C infection or
      cryoglobulinemia. The different aspects of "cirrhotic glomerulonephritis" are
      discussed and the need for searching for this underdiagnosed condition in
      patients with chronic liver disease is emphasized.

PMID- 9007160
TI  - The effect of acyclovir on the proliferative capacity of mononuclear cells from
      patients with chronic lymphocytic leukemia.
AB  - The cellular response of peripheral blood mononuclear cells (PBMC) from patients
      with B-cell chronic lymphocytic leukemia to increasing doses of acyclovir was
      examined by their capacity to incorporate 3H-TdR, and their response to
      phytohemagglutinin, concanavalin A and pokeweed mitogen. PBMC from healthy donors
      served as controls. Acyclovir caused a dose-dependent inhibition of 3H-TdR
      incorporation and mitogenic response in both leukemic and control cells, the
      effect on the latter being more pronounced. Although the results suggest that
      leukemic cells are less vulnerable than the controls, the toxic effect of
      acyclovir on the cellular immune response should be considered in the treatment
      of leukemic and other immunosuppressed patients.

PMID- 9007161
TI  - The choice of therapy in medically intractable trigeminal neuralgia.
AB  - Trigeminal neuralgia stands out as one of the few severe neuropathic pain states
      for which successful treatment options are available. Up to one-half of patients
      become refractory to medical therapy over time. At this point, the question of
      which intervention is appropriate becomes an important issue. A personal series
      of 150 patients treated between 1988 and 1995 is reviewed. Patients under 65
      years and in good general health underwent surgery for microvascular
      decompression of the trigeminal root; in the remaining 120 patients glycerol was
      injected percutaneously into the trigeminal cistern. The results in these two
      patient groups is presented and the rationale of choosing an operative versus a
      percutaneous procedure is discussed in light of the outcome in this series and in
      the literature.

PMID- 9007159
TI  - Impaired absorption of oral levodopa: a major cause for response fluctuations in
      Parkinson's disease.
AB  - Most patients with Parkinson's disease develop response fluctuations after
      several years of chronic treatment with levodopa. Accumulating evidence suggest
      that pharmacokinetic mechanisms are the cause of some subtypes of response
      fluctuations, especially the "delayed-on" and "no-on" phenomena. Evaluation of
      gastric emptying in Parkinson patients with and without response fluctuations
      revealed that those with fluctuations had a significant delay in gastric emptying
      compared to patients without fluctuations. Treatment with cisapride, a prokinetic
      drug, causes amelioration of these fluctuations. The optimal solution is to
      bypass the stomach completely and deliver levodopa parenterally. This was done by
      levodopa ethylester injections, which reduced latency to "on" and prolonged "on"
      duration in patients with severe response fluctuations. These data emphasize the
      role of the stomach as one of the causes for deterioration in Parkinson's
      disease.

PMID- 9007162
TI  - Merkel cell carcinoma in Israel.
AB  - Merkel cell carcinoma is a rare and highly malignant skin tumor. We present the
      first report on the clinical and epidemiologic characteristics of Merkel cell
      carcinoma in Israel. Our findings, including average age of 69 years at
      diagnosis, equal sex distribution, disease location on sun-exposed skin, and an
      overall 3 year survival of 58%, are consistent with the data reported in the
      literature. Unique findings in our study were the predominance of Ashkenazic Jews
      and the excessive rate of second malignancies. This initial report on Merkel cell
      carcinoma in Israel emphasizes the need for increased awareness of this
      aggressive and potentially lethal skin malignancy.

PMID- 9007163
TI  - HLA class I antigen expression in human solid tumors.
AB  - The expression of HLA class I antigens was studied by immunohistochemistry in
      various tumors in correlation with clinicopathologic characteristics. Reduced
      expression was observed in germ cell testicular cancer, kidney, prostate, gastric
      and colon cancer, and was associated with tumor aggressiveness, grade and
      penetration of the tumor through the organ wall. In bladder cancer reduced
      expression was associated with poor survival. Irradiation of brain tumors
      resulted in an increase in class I expression. Soluble class I levels were
      studied in breast and colon cancer patients and were found to be high in those
      with metastatic disease. The clinical relevance of reduced class I levels are
      discussed.

PMID- 9007164
TI  - Effect of green argon (514 nm) laser exposure on rose bengal-stained guinea pig
      cornea.
AB  - Our purpose was to study the effect of continuous wave (CW) green argon laser
      (514 nm) exposure on rose bengal-stained cornea. Following staining with rose
      bengal (1%), the corneas of 48 albino guinea pigs were exposed to different power
      levels of argon laser, ranging between 0.04 and 0.8 W. The beam diameter ranged
      between 50 and 200 microns, and exposure time was 0.1 sec. Histology revealed
      minimal tissue coagulation at 0.05 W and 50 microns. Moderate coagulation of the
      anterior stromal lamellae was found at power levels of 0.07-0.6 W and a beam
      diameter of 100-200 microns. At power levels of 0.7 and 0.8 W, lamellar
      disruption was also noted. Our data indicate that 1% rose bengal is a good
      photosensitizer for superficial corneal stromal photocoagulation.

PMID- 9007166
TI  - Pathologic evaluation of fresh tissue from neurosurgical biopsies: technical and
      interpretational aspects.
AB  - A number of rapid techniques are available for intraoperative consultations on
      neurosurgical biopsies. The press preparation, introduced in this report, is a
      less traumatizing variation of smash/smear/crush techniques for fresh tissue. It
      can be prepared in less than 5 min. The purpose of the present report is to
      describe the technique and its key applications. An additional goal of this study
      was to identify novel differential diagnostic possibilities that may arise in
      these preparations. It was found that press preparations clearly maintain the
      tissues' cytologic features, while key histologic components are preserved in
      larger fragments. To exemplify the findings using this approach, the features of
      astrocytomas are described. It is concluded that the press preparation is a rapid
      and informative means to facilitate pathologic evaluation of fresh tissue from
      neurosurgical biopsies.

PMID- 9007165
TI  - Gallopamil reduces the post-transplantation acute tubular necrosis in kidneys
      from aged donors.
AB  - Due to a shortage of suitable kidneys for transplantation there has been an
      increase in the use of kidneys taken from old and marginal donors, which has led
      to a high incidence of acute tubular necrosis. Several reports suggest that the
      administration of calcium channel blockers improves the initial function after
      renal transplantation. We conducted a randomized, double-blind placebo-controlled
      trial to study the effect of the calcium channel blocker gallopamil on the
      incidence and course of acute tubular necrosis following cadaveric renal
      transplantation. A trend developed showing a decrease in episodes of acute
      tubular necrosis in gallopamil versus placebo, and became statistically
      significant when the outcome of kidneys from donors older than 50 years was
      analyzed separately [gallopamil 6/14 (42%) vs. placebo 10/11 (91%), P <0.01
      corrected chi2]. We conclude that pre-transplantation renal graft perfusion and
      post-transplantation recipient treatment with gallopamil reduces the incidence of
      post-transplantation acute tubular necrosis, particularly in kidney taken from
      older donors.

PMID- 9007167
TI  - Non-traditional risk factors for atherosclerosis in high risk children.
AB  - Non-traditional risk factors for atherosclerosis were examined in children whose
      fathers suffered from myocardial infarction up to age 48. Factors examined were
      hyperinsulinemia, insulin resistance, lipoprotein(a) [Lp(a)], fibrinogen,
      cardiovascular hyperreactivity, and autonomic nervous system dysfunction.
      Hyperinsulinemia was present in five cases (9%) and hypoinsulinemia in two.
      Insulin output following glucose load was significantly higher in obese children
      compared with controls. There was an increase in Lp(a) alone in 14 cases (24%)
      and with low density lipoprotein in 6 cases. Increased fibrinogen and positive
      correlation with insulin abnormality was present in 29% (76% females) (P >0.02).
      Cardiac hyperreactivity (increased systolic blood pressure) was present in 9% and
      increased blood pressure and pulse rate in 17%. Holter monitoring pattern was
      sympathetic in 39% and parasympathetic in 47% of cases. Thus a number of non
      traditional risk factors were found to be higher than normal in a relatively
      large number of children at high risk for atherosclerosis, with 25 children
      having more than three risk factors.

PMID- 9007168
TI  - The choleretic effect of nonsteroidal anti-inflammatory drugs in total parenteral
      nutrition-associated cholestasis.
AB  - Cholestasis is a frequent problem in patients on total parenteral nutrition (TPN)
      therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, cause
      choleresis in animals. We studied the effect of aspirin on bile flow and bile
      salt secretion in TPN-associated cholestasis in rats. Four groups of 6-10 animals
      each received either 154 mM NaCl (saline) or 2.5% amino acid solution (TRAVASOL,
      Travenol, Israel) and 10% glucose i.v. (TPN) for 3 h. During the second and third
      hours, taurocholate, the main bile salt in rats, was infused at a rate of 10
      micromol/min per kg to prevent bile salt pool depletion. Aspirin, one of the main
      NSAIDs, was infused during the last 2 h into animals with or without TPN
      treatment at a rate of 100 mg/kg. Bile was directly collected from the common
      bile duct for 3 h. Rats given TPN showed a significant reduction in bile flow and
      bile salt secretion rate compared to control groups: 20.89 vs. 29.60 microl/min
      per kg (P <0.02) and 0.37 vs. 0.65 micromol/min per kg (P <0.0001), respectively.
      Aspirin had a significant choleretic effect and was able to overcome the bile
      flow and bile salt secretion rate reduction caused by TPN; 33.07 vs. 20.89
      microl/min per kg (P <0.002) and 0.66 vs. 0.37 micromol/min per kg (P <0.0001),
      respectively. These results may have clinical implications for TPN-associated
      cholestasis.

PMID- 9007169
TI  - Necrotizing enterocolitis: the impact of the establishment of a Department of
      Pediatric Surgery on the Beilinson Medical Campus.
AB  - Necrotizing enterocolitis (NEC) is the most commonly acquired gastrointestinal
      emergency in neonates. We retrospectively surveyed all cases of confirmed NEC
      treated at the Beilinson Medical Center (BMC) (now Rabin Medical Center,
      Beilinson Campus) during a 12 year period to determine whether the establishment
      of a department of pediatric surgery has influenced the treatment and outcome of
      NEC patients. Of the 48 patients, 23 were patients treated in the "early period",
      1982-87, when surgery was performed in the Department of General Surgery by staff
      trained in pediatric surgery (group I), and 25 were treated in the "later period"
      1988-93, in the same neonatal intensive care unit, with surgical supervision by
      the new Department of Pediatric Surgery (group II). We found that 32% of the
      group II patients were of extremely low birthweight (<1,000 g) compared with 13%
      of group I. They also had lower Apgar scores, and a higher percentage needed
      respiratory assistance (56 vs. 26%, P = 0.02). All those infants of group II who
      had been born in other hospitals and were transferred to BMC for treatment were
      in an advanced state of disease and all required surgery. Total mortality
      decreased from 22% in group I to 8% in group II. This decrease may be attributed
      to improved supportive treatment in the neonatal intensive care unit, earlier
      surgery for NEC based on relative rather than absolute indications, higher rates
      of primary resection, and better postoperative care. Our review indicates that
      the establishment of a Department of Pediatric Surgery at the BMC has contributed
      to the considerable improvement in NEC outcome in our center.

PMID- 9007170
TI  - Induction of tumor necrosis factor and nitric oxide by Shigella strains isolated
      from patients with or without neurologic manifestations.
AB  - The pathogenesis of the Shigella-associated neurological symptoms is unclear. We
      examined the potential role of host factors. Sonicates of Shigella strains
      isolated from children with and without neurologic disturbances were compared
      regarding their ability to induce tumor necrosis factor (TNF) and nitric oxide
      (NO) in vitro, in mouse macrophage J744 cell line. The mean concentrations of TNF
      (14.6 vs. 4.4 ng/ml) and NO (7.4 vs. 3.7 microM) induced were higher in response
      to strains isolated from children with neurologic complications; the differences
      were not statistically significant. TNF was also measured in plasma of children
      with shigellosis, and was found to be elevated in all patients. The mean
      concentration of TNF in plasma of children with neurologic manifestations was
      higher than that of children with no neurologic symptoms (450 vs. 138 pg/ml, P
      <0.05). It is concluded that TNF and NO may play a role in the development of
      neurologic manifestations of shigellosis.

PMID- 9007171
TI  - Immune deficiency in glycogen storage disease type 1B.
AB  - Patients with glycogen storage disease type 1B present the clinical features of
      glycogen storage disease type 1A. In addition, they are susceptible to recurrent
      bacterial infection and have recurrent oral ulcers and occasionally Crohn's-like
      disease. There features are due to immune dysfunction caused by a combination of
      neutropenia and impaired phagocytic functions.

PMID- 9007172
TI  - Parental anxiety in febrile convulsions.
AB  - Febrile convulsions can cause extreme anxiety to parents. Factors associated with
      parental anxiety and its relief during and after admission of their child for
      simple febrile convulsions were studied by questionnaire. Of the 70 parents
      approached 46 responded (66%), all of whom reported feeling anxiety. Factors
      directly associated with parental anxiety were lack of knowledge regarding the
      management of seizures and the performance of a spinal tap or EEG. There was no
      correlation between a previous seizure in the same child or in a first-degree
      relative and a decrease in anxiety in the present seizure. Hospital admission of
      the child yielded no relief of anxiety in 27.3% and some relief in 34.1%. Staff
      activity was insufficient regarding parental instruction in handling the child in
      the event of a recurrence. About two-thirds of the parents wished to continue
      neurologic follow-up after discharge, and about one-half preferred that the child
      be treated with anticonvulsants. Our findings show that a very intensive effort
      is required to relieve parental anxiety after febrile convulsions. It is
      suggested that routine parental preventive education in this area be conducted in
      well-baby clinics.

PMID- 9007173
TI  - Demographic characteristics of the Israeli Arab community in connection with
      consanguinity.
AB  - In a previous nationwide survey of the Israeli Arab community we showed that 44%
      of all marriages are consanguineous. Further analysis of the data from this
      previous survey was undertaken, and we defined six demographic characteristics
      that may be associated with consanguinity or non-consanguinity in the marriages.
      Of these, we found a significant correlation (P <0.001) with religion (for
      Moslems, odds ratio 1.7), consanguinity in parents' marriages, and the
      respondent's attitude towards consanguineous marriage. The educational level
      achieved was not a major factor in the type of marriage chosen. These findings
      should enable us to plan specifically designed educational and counseling
      programs with a view to reducing the overall incidence of consanguineous
      marriage.

PMID- 9007174
TI  - Cutaneous malignant melanoma in young adults under age 30.
AB  - Epidemiologic and clinicopathologic features of malignant melanoma in 129
      patients (44 males, 85 females) aged < or = 30 years between 1961 and 1992 were
      investigated. The number of new young melanoma patients (29 of 216 during the
      1960's) declined to 52 of 676 during the 1980's. Predominant sites were legs
      among females, and head, neck and back among males. Nodular type lesions (56.6%)
      outnumbered superficial spreading tumors (38.8%). Thirty-one patients (24%) died
      of melanoma (median survival 2.9 years), with higher male mortality. A decrease
      in mortality rate was observed over the decades. The relationship between various
      parameters was analyzed. Nodular lesions were smaller and thicker than
      superficial spreading lesions, occurred more frequently in males, and carried a
      worse prognosis (34% mortality) than superficial spreading type tumors (14%);
      mortality rate was higher for thick (>4 mm) and for large tumor volumes (>300
      mm3) vs. thin and small sized lesions, respectively (P = 0.000 for each). Average
      tumor thickness and volume declined throughout the last three decades. From the
      data obtained, a typical profile of a young melanoma patient is drawn.

PMID- 9007175
TI  - Female breast burns: conservative treatment with a reconstructive aim.
AB  - We retrospectively reviewed 421 burn patients treated in our burn unit in the
      past 3 years, focusing on breast burns in female patients. The aim of our study
      was to review the epidemiology, establish the mechanism of breast burn
      occurrence, and review the treatment plan. We evaluated 138 female burn patients,
      38 (9%) of whom had non-isolated breast burns. In this group 25 burns (66%) were
      caused by scalds and 13 (34%) by fire. Scalds were responsible for first- to
      second-degree burns (50%), and cooking oil and fire for second- to third-degree
      burns (50%). A statistically significant difference was noted in the incidence of
      breast burns, which occurred mainly in late summer and fall (P = 0.03). There was
      a direct correlation between burn depth and duration of hospitalization, with
      average hospitalization time of 1.45 days for each percent of burn. Most breast
      burns were domestic, with children constituting the majority of the victims. Most
      breast burn patients were treated conservatively. Breast deformity on recovery
      varied in severity from minor deformity correctable with simple breast reduction
      surgery in older patients to severe deformity requiring further reconstructive
      surgery in infants.

PMID- 9007177
TI  - The role of nuclear scintigraphy of suspected bile duct injury following
      laparoscopic cholecystectomy.
AB  - Nuclear scintigraphy is a rapid and non-invasive tool for the diagnosis of
      suspected bile duct injury following laparoscopic cholecystectomy. We describe
      our experience with this technique in 19 out of more than 1,000 cases of
      laparoscopic cholecystectomy in our department. Of the five patients in whom
      nuclear scintigraphy revealed abnormalities, three showed bile leak to the
      peritoneum and underwent immediate laparotomy. Only one of these required
      choledochojejunostomy; in the others the leak would have closed spontaneously
      without surgery. In the remaining two patients there was apparently no passage to
      the duodenum on nuclear scintigraphy. Endoscopic retrograde
      cholangiopancreatography (ERCP) performed in one showed a normal bile duct. In
      the other patient, repeated scintigraphy done 12 h later, prior to ERCP, showed
      normal passage to the duodenum. Our experience indicates that laparotomy could
      have been avoided had ERCP been performed first. Therefore, we suggest that if
      nuclear scintigraphy fails to demonstrate passage to the bowel or shows a bile
      leak, ERCP is indicated.

PMID- 9007176
TI  - Treatment decisions in thyroid surgery based upon ultrasonography.
AB  - Between 1991 and 1994, 600 thyroidectomies were performed at the Beilinson
      Medical Center in Israel, 120 of which were due to malignancies. Routine
      preoperative and follow-up ultrasound examinations were performed in 100 cases. A
      prospective study comparing preoperative ultrasonic and operative findings
      revealed that ultrasound offered significant preoperative information that could
      alter operative decisions. Ultrasound also proved to be a valuable tool in follow
      up. Based on ultrasound findings, patients were salvaged at an early stage of
      recurrent disease.

PMID- 9007178
TI  - Does lipid infusion affect bile composition in humans?
AB  - A prospective study was performed to investigate the effect of short-term lipid
      infusion on bile composition and its lithogenicity in humans. The study group
      comprised 44 patients scheduled for laparotomy. The patients were hospitalized 48
      h prior to elective surgery and randomized to be infused with a lipid emulsion of
      either long chain triglycerides (LCT) or a mixture of medium and long chain
      triglycerides (MCT/LCT) for 6 h of each 24 h, or with glucose-saline. Bile
      samples were obtained by puncture of the gallbladder during operation. In non
      gallstone patients, both lipids caused an elevation of biliary cholesterol and
      phospholipids, but this effect was more pronounced and significant (P <0.001)
      only with the mixture of MCT/LCT emulsion. The fatty acid composition of biliary
      phospholipids was not affected by either lipid infusion. The Cholesterol
      Saturation Index increased significantly (P <0.005) with the MCT/LCT emulsion and
      there was insignificant shortening in the nucleation time. In contrast to
      patients with cholelithiasis, no effects could be demonstrated on gallbladder
      bile composition, cholesterol saturation index, nucleation time, or fatty acid
      composition of phospholipids. The effects of both lipid emulsions on plasma
      lipids and lipoproteins were similar in all groups. Our results indicate that
      lipid emulsions containing MCT/LCT induce lithogenic changes in the composition
      of human bile. We propose that the lack of effect of lipid infusion on bile
      composition in patients with cholelithiasis may be due to precipitation of excess
      cholesterol in the gallbladder of cholesterol gallstone patients whose bile is
      already saturated. These findings imply that patients with cholesterol gallstones
      cannot be grouped with non-gallstone patients in studies of alterations of bile
      composition.

PMID- 9007179
TI  - Healing of the esophageal suture line: does it differ from the rest of the
      alimentary tract?
AB  - We investigated the healing pattern of the esophageal suture line in rats. Fifty
      male wistar rats were divided into experimental (n = 40) and control (n = 10)
      groups. The rats in the experimental group underwent esophogostomy at the
      abdominal esophagus, which was immediately sutured, and sacrificed 2, 4, 7 and 14
      days later. Esophageal bursting pressure and hydroxyproline content were
      determined in both groups. The measured bursting pressures in the experimental
      group on days 2, 4, 7 and 14 were (mean +/- SD) 78 +/- 35, 95 +/- 12, 1,163 +/-
      98 and 1,224 +/- 22 cm H2O, respectively, and 1,308 +/- 87 cm H2O in the control
      group (P <0.05 vs. all the experimental group values). The hydroxyproline content
      in the experimental group on days 2, 4, 7 and 14 were 13.9 +/- 2.1, 12.53 +/-
      2.68, 15.6 +/- 0.85 and 17.75 +/- 5.65 microg/mg, respectively, and 27.88 +/- 2.5
      microg/mg in the control group (P <0.05 vs. all the experimental group values).
      We conclude that the esophagus demonstrates the same healing pattern as the rest
      of the alimentary tract, but its healing seems to occur at a slower pace.

PMID- 9007180
TI  - Acute bacterial peritonitis: permeability of cephalosporins in the peritoneal
      cavity.
AB  - Acute bacterial peritonitis is a common surgical disease treated with fluid
      resuscitation, surgery and antibiotics. The choice and use of antibiotics is an
      important supplement of therapy. Cephalosporins are among the most frequently
      used drugs for this condition. Although there is evidence that these agents reach
      the peritoneal cavity under normal conditions, no data are available regarding
      their delivery and concentration during acute secondary bacterial peritonitis. In
      order to determine the effectiveness of these agents in such cases, we studied
      the diffusion of three generations of cephalosporins--cefazolin, cefonicid and
      cefotaxime--into the peritoneal cavity during controlled bacterial peritonitis in
      rats. Our results show that all three drugs reached therapeutic concentrations in
      the peritoneal fluid; the highest concentration was obtained by the third
      generation cefotaxime.

PMID- 9007181
TI  - Late solitary pancreatic metastasis from renal cell carcinoma.
AB  - A 76-year-old woman was admitted for a pancreatic mass. Twenty-one years
      previously she had undergone a left nephrectomy for renal cell carcinoma. A
      computerized tomography-guided needle biopsy of the pancreatic mass raised the
      suspicion of metastatic renal cell carcinoma. Final pathologic examination of the
      resected mass after distal subtotal pancreatectomy confirmed the preoperative
      diagnosis of metastatic renal cell carcinoma.

PMID- 9007182
TI  - Surgical results in cardiac patients over the age of 80 years.
AB  - Improved medical care over the years has increased life expectancy and
      consequently the number of aged persons suffering from cardiac disease. During
      the past 3 years, 42 consecutive octogenarians, with an average age of 82.1
      years, were evaluated. Thirty patients had coronary artery bypass graft surgery
      (CABG), 5 had aortic valve replacement (AVR), and 7 had combined CABG-AVR
      surgery. Among the ischemic patients 70% had suffered from unstable angina
      pectoris, and an average of 2.78 +/- 1 grafts per patients were performed. The
      left internal mammary artery was used in 12 patients (32%). Overall mortality was
      7.1% (3 patients), while operative mortality was 2.4% (1 patient). Another two
      patients who expired during the 34 month follow-up period underwent AVR. The
      average hospitalization period was 10.2, 12 and 17.6 days for patients undergoing
      CABG, combined CABG-AVR, and AVR alone, respectively. Complications occurred in
      10 patients (24%) and included neurologic deficits (in 2 patients), severe wound
      infection (in 2), cardiac arrhythmia (in 4), renal failure (in 1) and adult
      respiratory distress syndrome (in 1). The use of the left internal mammary artery
      was not associated with an increased incidence of complications. The low rate of
      mortality and major complications and the substantial improvement in quality of
      life led us to conclude that, when indicated, surgical treatment should be
      offered to selected elderly individuals who otherwise are in good physical and
      mental health.

PMID- 9007183
TI  - Use of the modified technique of ultrafiltration in pediatric open-heart surgery:
      a prospective study.
AB  - The use of cardiopulmonary bypass (CPB) in children is associated with
      significant morbidity due to the accumulation of an excessive amount of water.
      This can be decreased by massive diuresis, peritoneal dialysis, or conventional
      ultrafiltration technique (CUF) during bypass. However, we were dissatisfied with
      their effect on the outcome of our young patients, and recently began to use the
      modified technique of ultrafiltration (MUF) with good results. MUF was carried
      out for 15 min after completion of CPB to a hematocrit of 40%. Eighty patients
      were equally divided into two groups--MUF (group A) and control (group B)--and
      prospectively studied. There was one death in group A and two deaths in group B.
      The chest was left open in one patient in group A and in three patients in group
      B. At the end of MUF, the cardiac size was smaller, performance was better, and
      systemic blood pressure was higher in group A. Hematocrit levels in the two
      groups were similar during preoperative and CPB time, but post-CPB hematocrit in
      group A was significantly higher, 39.4% mean (range 35-50) vs. 28.5 (range 22-38)
      in group B (P <0.05). Blood loss was 10.56 ml/kg per 24 h (2-48.7) in group A vs.
      20.8 (4.5-105.6) in group B (P <0.05). Blood transfused was 7.2 ml/kg per 24 h (0
      29) in group A vs. 17.3 (3.1-49) in group B (P <0.05). Colloids transfused were
      16.7 ml/kg per 24 h (0-64) in group A vs. 27.5 (0-58.6) in group B (P <0.05). No
      significant difference was found in urine output or the use of diuretics between
      the two groups. MUF results in better hemodynamic status in children, with the
      added advantage of less transfused blood and blood products. We believe that the
      use of accepted surgical techniques in combination with MUF will further improve
      the outcome of complex cardiac malformations.

PMID- 9007184
TI  - First successful implantation of an artificial heart in Israel: circulatory
      support for 90 days.
AB  - We report the first successful implantation in Israel of an artificial heart in a
      47-year-old man. The patient was on the waiting list for a transplant as his left
      heart had ceased to function. This prosthetic heterotopically placed ventricle
      kept the patient alive for 3 months. Unfortunately, during this period no
      suitable donor became available.

PMID- 9007185
TI  - "Veno-Press"--a new sequential intermittent pneumatic device for the prevention
      of perioperative deep vein thrombosis.
AB  - The prevention of peri-operative deep vein thrombosis (DVT) and the potentially
      hazardous pulmonary embolism that may follow is still a major medical issue.
      Intermittent pneumatic compression is one of the many methods currently in use
      for this purpose. No information is available, however, regarding the venous flow
      alterations that occur during employment of a pneumatic compression device under
      general anesthesia. The aim of this study is to delineate these venous flow
      variations and to determine the optimal pump setting for the prevention of
      operative venous stasis and its sequelae, postoperative DVT. A new sequential
      intermittent pneumatic device, the "Veno-Press", was applied on 20 volunteers of
      whom 10 were undergoing surgery unrelated to the lower limbs, during the pre
      anesthesia and during general anesthesia. The venous velocity patterns over the
      femoral vein were depicted via duplex scanning under different pressure and
      rhythm settings of the device. The "Veno-Press" induced a marked augmentation in
      venous blood velocity flow. A further 10-30% augmentation was noted when the
      patients were under general anesthesia, as well as a 10-30% increase in the
      femoral vein diameter. None of the patients developed postoperative DVT. This
      device is a very efficient tool for augmentation of venous blood velocity,
      especially during general anesthesia. Its effectiveness is most probably the
      result of the compressive action over the relaxed--and hence enlarged--capacitant
      veins of the anesthetized patient. We suggest that the "Veno-Press", if properly
      timed, is very efficient in venostasis prevention, leading presumably to a
      decline in the occurrence of DVT and pulmonary embolisms in the surgical patient.

PMID- 9007186
TI  - Patient satisfaction in two departments of surgery in a community hospital.
AB  - Patient satisfaction with medical and nursing care was evaluated in two surgical
      departments of a community teaching hospital in Petah Tikva (now called Rabin
      Medical Center, Golda Campus). The interview, conducted before the patients were
      discharged, related to their perception of the preoperative period, the attitude
      of the personnel in the operating room before anesthesia was administered, and
      their satisfaction during the postoperative period. The questionnaire completed
      by the interviewer included questions on the time that elapsed from admission to
      the first examination by a physician and a nurse, whether the patient received
      information about the operation and its possible complications, was examined by
      the anesthetists, received details regarding the results of the surgical
      procedure, and what his or her impression was of the attitude of the nursing
      staff. The patients were asked to rate their evaluation on a scale from 1 to 10.
      The results showed high satisfaction with the services provided and were similar
      for both departments. The small number of patients whose satisfaction rated from
      5 to 8 complained about the sanitary conditions in the toilets, the overcrowded
      departments, and the lack of sufficient number of registered nurses during the
      night shifts.

PMID- 9007187
TI  - Local-circuit neurones in the medial prefrontal cortex (areas 25, 32 and 24b) in
      the rat: morphology and quantitative distribution.
AB  - This paper is a light microscopical study describing the detailed morphology and
      quantitative distribution of local circuit neurones in areas 25, 32, and 24b of
      the medial prefrontal cortex (mPFC) in the rat. Cortical interneurones were
      identified immunocytochemically by their expression of calretinin (CR),
      parvalbumin (PV), and calbindin D-28k (CB) immunoreactivity. Neurones
      immunoreactive for gamma-aminobutyric acid (GABA) were also investigated, as were
      interneurones containing reduced nicotinamide adenine dinucleotide phosphate
      (NADPH) diaphorase activity. Several distinct classes of CR+, PV+, and CB+
      neurones were identified; the most frequent were: bipolar/bitufted CR+ cells in
      upper layer 3; multipolar PV+ neurones in layers 3 and 5; and bitufted/multipolar
      CB+ neurones in lower layer 3. CB+ neurones resembling Martinotti and
      neurogliaform cells were also present in layers 5/6. The morphologies and depth
      distributions of each cell type were consistent across the three areas of mPFC
      studied. Seven classes of diaphorase-reactive mPFC neurone are described; these
      cells were composed about 0.8% of the total neurone population and had a peak
      distribution located in mid- to lower layer 5 in each area. In areas 32 and 25,
      three defined bands of diffuse NADPH diaphorase staining were located in layer 2
      and in upper and deep layer 5. Diaphorase reactivity was very infrequently
      colocalised with either CR, PV, or CB immunoreactivities. The numerical densities
      of neurones (N(V), number of cells per mm3) in each layer were calculated
      stereologically. The mean total neuronal N(V) estimate for areas 25, 32, and 24b
      was 51,603 +/- 3,324 (mean +/- S.D.; n = 8). Significant interareal differences
      were detected. From cortical thickness data and neuronal N(V) estimates, the
      absolute number of neurones under 1 mm2 of cortical surface (N(C)) have been
      derived. The mean N(C) value for areas 25, 32, and 24b was 57,328 +/- 7,505
      neurones. In immunolabelled Nissl-stained sections, CR+ neurones constituted an
      overall 4.0%, PV+ cells 5.6%, and CB+ 3.4% of the total neurone populations in
      mPFC. GABA+ cells represented a mean of 16.2% (14.8-17.2%) of neurones in areas
      25, 32 and 24b. The absolute numbers of CR+, PV+, CB+, and GABA+ neurones within
      individual layers in a column of cortex under 1 mm2 of cortical surface (N(L))
      have also been derived, with significant interareal differences in N(L) values
      being detected. The data provide the structural basis for a qualitative and
      quantitative definition of local cortical circuits in the rat mPFC.

PMID- 9007189
TI  - Stress-induced activation of nitric oxide-producing neurons in the rat brain.
AB  - Nitric oxide (NO) is a gaseous neurotransmitter that may mediate a decrease in
      sympathetic output to the periphery. This implication predicts that NO-producing
      neurons in the brain are activated in animals experiencing increased levels of
      sympathetic activity. To test this prediction, we subjected three groups of
      experimental rats to differing levels of environmental stimulation for 1 hour:
      minimal stimulation, moderate stimulation, and restraint stress. NO-producing
      neurons were histochemically visualized in sections of the brain, and activation
      of these neurons was assessed according to the neuronal expression of the
      immediate early gene c-fos. Constitutive activation of NO-producing neurons was
      found in the hypothalamus (paraventricular and supraoptic nuclei), dorsal raphe
      nuclei, and spinal nucleus of the trigeminal nerve of minimally stimulated rats.
      When animals were subjected to a novel environment (moderate stimulation),
      additional NO-producing neurons were activated in the medial septum, medial
      amygdala, hypothalamic nuclei (lateral, periventricular, and posterior),
      colliculi, nucleus raphe obscurus, medial vestibular nucleus, nucleus of the
      tractus solitarius, and several components of the ventrolateral medulla.
      Restraint stress caused the activation of NO-producing neurons in all of these
      areas, often in increasing numbers, and the activation of additional NO-producing
      neurons in the diagonal band of Broca, lateral and medial preoptic areas,
      basomedial and basolateral amygdalar nuclei, hypothalamic nuclei (dorsomedial,
      retrochiasmatic supraoptic, and circularis), nucleus raphe pontus, lateral
      parabrachial nucleus, and pontine nuclei. Expressed as a proportion of NO
      producing neurons per section, the largest percentages (>20%) of double-stained
      neurons were found in the basolateral amygdala (46%), hypothalamic
      paraventricular nucleus (35%), corpora quadrigemina (estimated at 40%), dorsal
      raphe (45%), nuclei raphe pontus (33%) and obscurus (63%), lateral parabrachial
      nucleus (22%), medial vestibular nucleus (25%), lateral division of the nucleus
      paragigantocellularis (26%), and lateral reticular nucleus (35%). Evidence from
      other studies increasingly supports the concept that NO plays a generalized role
      in autonomic regulation by decreasing sympathetic output. Our results show that
      more NO-producing neurons were activated during stress than during minimal or
      moderate levels of stimulation. Together, the evidence suggests that NO is a
      neurochemical messenger that is utilized by individual autonomic neurons as the
      organism responds to increased levels of sympathetic activity.

PMID- 9007188
TI  - Early emergence of photoreceptor mosaicism in the primate retina revealed by a
      novel cone-specific monoclonal antibody.
AB  - We have examined the emergence of the photoreceptor mosaic in fetal macaque
      monkeys by using a novel monoclonal antibody, 7G6, that recognizes all cones in
      the adult primate retina. In the fetal retina, however, between embryonic (E) day
      80 and E130, some opsin-positive cones were not labeled by 7G6. Double-labeling
      experiments revealed that though long and middle wavelength-sensitive fetal cones
      are 7G6-positive, a subset of short wavelength-sensitive cones are delayed in
      their acquisition of 7G6 immunoreactivity. Heterogeneity in cone labeling with
      7G6 was evident at all fetal ages. The onset of 7G6 immunoreactivity,
      surprisingly, precedes both the expression of the cone opsins and the formation
      of synaptic contacts in the outer plexiform layer. Specifically, a population of
      cones was labeled in the periphery of the E65 retina, concomitant with ongoing
      cone genesis. Moreover, early-differentiating 7G6-positive cones are organized
      into a regular array in immature, peripheral regions of the fetal retina
      indicating that the spatial arrangement of cones is initiated either during
      active cone proliferation or the initial differentiation of these cells. These
      results suggest that the periodic spacing of cones in the primate retina emerges
      autonomously within the photoreceptor layer, prior to the formation of synaptic
      connections within the retina or with the brain.

PMID- 9007190
TI  - Development of the organ of Corti in horseshoe bats: scanning and transmission
      electron microscopy.
AB  - The late prenatal and early postnatal development of the organ of Corti were
      studied in the horseshoe bat (Rhinolophus rouxi) by using scanning and
      transmission electron microscopy. Arrangements and dimensions of stereocilia
      bundles, together with their contacts with the tectorial membrane, were found to
      be adult-like shortly before birth, and thus before the biological onset of
      hearing (3-5 days after birth). During the first postnatal week, there were baso
      apical gradients in disappearing kinocilia on inner hair cells (IHC), microvillis
      of supporting cells, and marginal pillars. The lower basal cochlear turn was
      mature with respect to these regressing structures at 3 days after birth, the
      apical turn at 10 days after birth. At birth, cytodifferentiation was found to be
      completed, and the tunnel of Corti and innermost spaces of Nuel had opened. The
      ultrastructure of IHCs was not markedly different from that at later ages. In
      outer hair cells (OHC), the adult-like regular arrangement of a single layer of
      subsurface cisternae and pillars was seen as soon as protrusions of supporting
      cells had withdrawn from the lateral wall of OHCs (basal turn at birth and
      throughout the cochlea 2 days after birth). Numerous efferent endings contacted
      the somata of IHCs up to the second postnatal week. Since the medial
      olivocochlear system is absent in horseshoe bats, the adult-like innervation
      pattern of OHCs was established at the biological onset of hearing. During the
      first 2 postnatal weeks, the cytoskeleton of pillar and Deiters cells, and the
      specialized Deiters cups developed. The organ of Corti appeared adult-like at 14
      days, apart from the persistence of a reduced tympanic cover layer attached to
      the basilar membrane. Morphological data support physiological findings that the
      first broadly tuned auditory responses arise from the basal turn. The distinct
      low to high frequency gradient in development of sensitivity during the first 2
      postnatal weeks of the horseshoe bat was not, however, matched by morphological
      gradients, and it would appear that the development of the cytoskeleton of
      supporting cells contributed to the establishment of tuning in the auditory
      fovea. Adult-like morphology of the organ of Corti coincided with the emergence
      of sharply tuned responses from the auditory fovea, but there was no clear-cut
      correlate for the shift in tuned foveal frequency representation that occurred
      during the following 3 weeks.

PMID- 9007191
TI  - Immunocytochemistry and distribution of parabrachial terminals in the lateral
      geniculate nucleus of the cat: a comparison with corticogeniculate terminals.
AB  - We used immunohistochemistry in cats to demonstrate the presence of brain nitric
      oxide synthase (BNOS) in cholinergic fibers within the A-laminae of the lateral
      geniculate nucleus. We used a double labeling procedure with electron microscopy
      and found that all terminals labeled for choline acetyltransferase (ChAT) in the
      geniculate A-laminae were double labeled for BNOS. Also, some interneuron
      dendrites, identified by labeling for gamma-aminobutyric acid (GABA), contained
      BNOS, but relay cell dendrites did not. We then compared parabrachial and
      corticogeniculate terminals, identifying the former by BNOS/ChAT labeling and the
      latter by orthograde transport of biocytin injected into cortical area 17, 18, or
      19. All corticogeniculate terminals and most BNOS- or ChAT-positive brainstem
      terminals displayed RSD morphology, whereas some brainstem terminals exhibited
      RLD morphology. However, parabrachial terminals were larger, on average, than
      corticogeniculate terminals. We also found that parabrachial terminals were
      located both inside and outside of glomeruli, and they always contacted relay
      cell dendrites proximally among retinal terminals (the retinal recipient zone).
      In contrast, the cortical terminals were limited to peripheral dendrites (the
      cortical recipient zone). Thus, little if any overlap exists in the distribution
      of parabrachial and corticogeniculate terminals on the dendrites of relay cells.

PMID- 9007192
TI  - Mab22C11 antibody to amyloid precursor protein recognizes a protein associated
      with specific astroglial cells of the rat central nervous system characterized by
      their capacity to support axonal outgrowth.
AB  - Amyloid precursor protein (APP) is a transmembrane glycoprotein which is believed
      to promote neural cell adhesion, neural survival, and neuritogenesis. The present
      study was undertaken to determine whether APP could be detected within different
      types of astroglial cells present in the central nervous system (CNS) of neonatal
      or adult rats. The localization of this protein within glial cells was studied by
      using a monoclonal antibody (Mab22C11) that recognizes all APP isoforms and in
      addition cross-reacts with APP-like proteins. In the brain of neonatal rats,
      Mab22C11 immunostaining was associated with numerous elongated radial glia-like
      structures. In the intact brain and spinal cord of adult rats, Mab22C11
      immunostaining was associated with (i) numerous neuron-like structures and (ii)
      glial structures immunostained for glial fibrillary acidic protein (GFAP) and/or
      vimentin, including tanycytes mostly located in the mediobasal hypothalamus,
      fibrous astrocytes located in the white matter and ependymocytes bordering the
      ventricles. On the other hand, all the GFAP-immunostained astrocytes located in
      the grey matter were Mab22C11 negative. In the lesioned brain and spinal cord of
      adult rats, Mab22C11 immunostaining was associated with intensely GFAP
      immunostained reactive astrocytes located close to a surgical lesion, but not
      with those induced by Wallerian degeneration that appear at a distance from a
      lesion. Electron microscopic observations further indicated that in all these
      labeled astroglial cells, Mab22C11 immunostaining was mainly localized to the
      limiting plasma membrane and the membrane of intracytoplasmic cisternae and
      vesicles. These data indicate that Mab22C11 antibody induces strong
      immunostaining of specific astroglial cells of the neonatal and adult rat CNS
      that support axonal outgrowth, therefore suggesting that an APP-like protein
      associated with these cells participates in their axonal outgrowth promoting
      properties.

PMID- 9007194
TI  - Axonal regrowth after spinal cord transection in adult zebrafish.
AB  - Using axonal tracers, we characterized the neurons projecting from the brain to
      the spinal cord as well as the terminal fields of ascending spinal projections in
      the brain of adult zebrafish with unlesioned or transected spinal cords. Twenty
      distinct brain nuclei were found to project to the spinal cord. These nuclei were
      similar to those found in the closely related goldfish, except that additionally
      the parvocellular preoptic nucleus, the medial octavolateralis nucleus, and the
      nucleus tangentialis, but not the facial lobe, projected to the spinal cord in
      zebrafish. Terminal fields of axons, visualized by anterograde tracing, were seen
      in the telencephalon, the diencephalon, the torus semicircularis, the optic
      tectum, the eminentia granularis, and throughout the ventral brainstem in
      unlesioned animals. Following spinal cord transection at a level approximately
      3.5 mm caudal to the brainstem/spinal cord transition zone, neurons in most brain
      nuclei grew axons beyond the transection site into the distal spinal cord to the
      level of retrograde tracer application within 6 weeks. However, the individually
      identifiable Mauthner cells were never seen to do so up to 15 weeks after spinal
      cord transection. Nearly all neurons survived axotomy, and the vast majority of
      axons that had grown beyond the transection site belonged to previously
      axotomized neurons as shown by double tracing. Terminal fields were not re
      established in the torus semicircularis and the eminentia granularis following
      spinal cord transection.

PMID- 9007193
TI  - Prenatal development of calbindin D-28K and parvalbumin immunoreactivities in the
      human retina.
AB  - Two calcium binding proteins, calbindin D-28K (CB) and parvalbumin
      (PV),immunoreactivities were examined by immunocytochemistry in the retinas of
      human fetuses aged from 13 weeks (W) of gestation to term. CB- and PV
      immunoreactive products were both detectable at 13 W and appeared in all layers
      in a roughly inside-out order by 24 W. PV-immunostaining occurred in virtually
      all ganglion cells, most horizontal cells, and a few amacrine cells. CB
      immunoreactivity was found in most amacrine cells and some horizontal cells, and
      a subset of cells in the ganglion cell layer that were more frequent in the nasal
      than the temporal retina at 13-15 W. Bipolar cells were distinctly immunostained
      for CB by 24 W. Foveal cones showed faint CB labeling by 24 W and intense
      staining at 32 W. The patterns of CB- and PV-immunoreactivities by birth were
      similar to those at 32 W with the addition of faint CB-immunolabeling occurring
      beyond the fovea in the photoreceptors. A stronger expression of CB was seen in
      the nasal side of the optic nerve head from 13-24 W, peaking at 15 W. The results
      indicate that CB and PV expression in ganglion cells and inner nuclear layer
      neurons proceeds in parallel with their somal and process differentiation,
      suggesting a possible role for these proteins in neuronal maturation. The early
      expression of PV and CB in ganglion cell axons might be related to optic nerve
      outgrowth, including path-finding at the optic chiasm. CB expression in cones and
      other cells in the fovea may indicate that it is involved in foveal formation
      that occurs during the perinatal period.

PMID- 9007195
TI  - Ibotenic acid lesions of the substantia nigra pars reticulata ipsilateral to a
      visual cortical lesion fail to restore visual orienting responses in the cat.
AB  - Unilateral removal of all known visual cortical areas in the cat renders the
      animal hemianopic in the contralateral visual field as measured by visual
      perimetry and other behavioral tests. We have shown that visual orientation
      behavior can be restored to the previously blind hemifield by destruction of a
      critical zone in the substantia nigra pars reticulata contralateral to a cortical
      lesion (Wallace et al., J. Comp. Neurol. 296:222-252, 1990). The model proposed
      to explain this recovery postulates that damage to the crossed nigrotectal
      projection disinhibits the superior colliculus ipsilateral to the cortical lesion
      and this leads to recovery. If disinhibition can account for recovery, then
      destruction of the uncrossed nigrotectal projection, which is known to exert a
      tonic inhibition on the superior colliculus, should also result in recovery. We
      made unilateral visual cortical ablations and ipsilateral ibotenic acid lesions
      of the substantia nigra pars reticulata. Visual orienting behavior was assessed
      in animals for a period of 4 to 31 weeks. Contrary to the prediction of the
      model, we failed to observe a recovery of visual orienting behavior in the blind
      hemifield in any of 23 animals.

PMID- 9007196
TI  - Highlights from the University of California San Diego Center for AIDS Research.

PMID- 9007197
TI  - Mutations within the CD4-CDR-3-like loop allow replication in an immortalized T
      cell line of HIV type 1 viruses chimeric for envelope glycoproteins containing
      non-syncytium-inducing V3 loops.

PMID- 9007198
TI  - Loss of T cell receptor Vbeta repertoires in HIV type 1-infected SCID-hu mice.
AB  - Late-stage HIV-1 disease in humans has been associated with perturbations of the
      T cell receptor (TCR) Vbeta repertoire. It is not known if the observed loss of
      certain Vbeta families is attributable directly to HIV-1 infection or whether
      this is a consequence of multiple opportunistic infections. Putative HIV-1
      associated superantigens have been postulated to be the cause of the perturbed
      TCR Vbeta repertoire and the subsequent CD4+ T cell depletion in HIV-1-infected
      humans. In this study, we examined the human TCR Vbeta repertoire in SCID-hu
      mice, housed in a pathogen-free environment and infected with a molecularly
      cloned virus strain, to ascertain directly the effect of HIV-1 on the human TCR
      Vbeta repertoire in the absence of other infectious agents. We demonstrate that
      mock-infected human thymus/liver (Thy/Liv) implants in SCID-hu mice have complete
      TCR Vbeta repertoires, reflective of a normal human thymus. However, HIV-1
      infected implants in SCID-hu mice had depleted TCR Vbeta repertoires,
      corresponding with thymocyte depletion. These results indicate that HIV-1
      specific mechanisms are the cause of the TCR Vbeta repertoire depletion in
      infected implants. However, these thymocyte depletions were not restricted to
      specific TCR Vbeta subsets. These results are not consistent with the hypothesis
      that HIV-1 acts as a superantigen in vivo. The disruption of the TCR Vbeta
      repertoire in the human Thy/Liv implants of the SCID-hu mice suggests that HIV-1
      infection may be influencing T cell development in the thymus, contributing to
      both the overall CD4+ T cell depletion in AIDS and limited TCR repertoire
      diversity.

PMID- 9007199
TI  - VH gene use by HIV type 1-associated lymphoproliferations.
AB  - The pathogenesis of polyclonal HIV-associated lymphomas lacking traditional B
      cell cofactors (i.e., Epstein-Barr virus [EBV] infection, c-myc translocations)
      is poorly understood. A multistep pathogenesis model has been proposed in which
      polyclonal lymphomas represent an earlier stage in HIV-associated lymphomagenesis
      before the emergence of a dominant malignant clone. Chronically present antigens
      have been proposed as a likely stimulus for polyclonal B cell proliferation; if
      so, polyclonal lymphoma-associated immunoglobulins (Igs) should have molecular
      evidence of somatic hypermutation, a process by which antibody affinity
      maturation in response to chronic antigenic stimulation occurs. Molecular
      analyses of Ig heavy chain variable (V(H)) gene use by B cells in a polyclonal
      HIV-associated large cell lymphoma lacking EBV and c-myc rearrangement was
      undertaken. Eighteen randomly selected clones generated from RT-PCR yielded 15
      unique V(H) sequences, all of which were most homologous to only three previously
      identified germline V(H)1 genes. Two sets of clones (consisting of three and two
      clones, respectively) had identical V(H) gene sequences, and one pair of clones
      had identical third complementarity determining regions (CDR3s) but different
      V(H) gene sequences; eight clones were <95% homologous to their most related
      germline V(H)1 genes. We compared these results with Ig V(H)1 gene use by B cells
      present in a reactive hyperplastic lymph node obtained from an HIV-1-infected
      individual. Fifteen clones randomly selected from RT-PCRs yielded 15 unique V(H)1
      sequences, all of which were most homologous to 5 previously identified germline
      V(H)1 genes; 10 clones were <95% homologous to their most related germline gene.
      Binomial probability analysis revealed that only 1 of the 15 unique V(H)1
      sequences derived from the polyclonal lymphoma (i.e., 7%), as compared with 5 of
      15 unique V(H)1 sequences derived from the reactive lymph node (i.e., 33%), had a
      low probability of occurrence by random chance (p < 0.05). These data provide
      molecular evidence of polyclonality in an HIV-associated polyclonal lymphoma,
      demonstrate a qualitative difference in somatic hypermutations of Ig V(H) genes
      associated with malignant versus reactive B cell lymphoproliferations, and
      support an antigen-mediated multistep pathogenesis model of HIV-1-associated
      lymphomagenesis.

PMID- 9007200
TI  - V3 loop of human immunodeficiency virus type 1 suppresses interleukin 2-induced T
      cell growth.
AB  - We tested the effect of three linear or two loop peptides derived from the V3
      region of the HTLV-III BH10 clone or the SF2 strain of human immunodeficiency
      virus type 1 on IL-2-driven T cell proliferation. V3-BH10, which consists of 42
      amino acids and has a loop structure, suppressed IL-2-driven proliferation of all
      IL-2-dependent cells [Kit225, ED-40515(+), KT-3, 7-day PHA-blasts, and fresh
      peripheral blood mononuclear cells] tested, whereas it did not suppress the cell
      growth of IL-2-independent cell lines (Hut102, Molt-4, and Jurkat). This
      suppressive effect was also seen in IL-2-driven cell growth of CD8-positive
      lymphocytes purified from 7-day PHA-blasts, indicating that CD4 molecules were
      not required for the suppression. The treatment with anti-V3 loop monoclonal
      antibody (902 antibody) completely abolished the suppressive effect of V3-BH10.
      In addition, V3-BH10 generated the arrest of Kit225 cells and also purified CD8
      positive lymphocytes in G1 phase in the presence of IL-2. Neither chromatin
      condensation nor DNA fragmentation was detected in Kit225 cells cultured with V3
      BH10 and IL-2. V3-BH10 neither blocked radiolabeled IL-2 binding to IL-2
      receptors nor affected tyrosyl phosphorylation of several cellular proteins
      (p120, p98, p96, p54, and p38), which is immediately induced by IL-2 stimulation.
      However, V3-BH10 enhanced IL-2-induced mRNA expression of c-fos but not c-myc or
      junB. Thus, the binding of V3 loop of gp120 to the cell surface molecule(s)
      appears to affect intracellular IL-2 signaling, which leads to the suppression of
      IL-2-induced T cell growth.

PMID- 9007201
TI  - Synergy between human immunodeficiency virus type 1 and Epstein-Barr virus in T
      lymphoblastoid cell lines.
AB  - CR2 (CD21), the EBV receptor, was detected on three of four CD4-positive cell
      lines by indirect fluorescent labeling, and its corresponding mRNA was found by
      use of the reverse transcription-based polymerase chain reaction. To determine
      whether CR2 on CD4-positive cells was functional, their ability to be infected by
      EBV was analyzed. EBV DNA, EBV nuclear antigen 2 (EBNA-2A), and EBV-encoded small
      RNA (EBER1) transcripts could be detected in CR2-expressing CD4-positive cells
      following infection by the B95.8 strain of EBV. Analysis of the terminal region
      showed the EBV genome remained linear following infection, and copy number
      decreased with time. Since CD4-positive cell lines are targets for HIV-1
      infection, the effects of EBV infection on HIV-1 expression were analyzed. HIV-1
      replication was upregulated when CD4-positive cells were coinfected with EBV
      strain B95.8 but not P3HR-1K. These results suggested that EBNA-2 is involved in
      upregulation of HIV-1 expression in T lymphoblastoid cell lines. To test this
      hypothesis an EBNA-2-expression vector was transfected into T lymphoblastoid cell
      lines and HIV-1 expression measured. First, trans-activation of HIV-1 long
      terminal repeat (LTR) by Tat was enhanced by EBNA-2 type 1 expression. trans
      Activation of the HIV-1 LTR by Tat was also enhanced when CD4-positive cells were
      infected by EBV (strain B95.8) encoding an intact EBNA-2, but not by P3HR-1K with
      a deleted EBNA-2. In addition, CD4-positive cell clones stably expressing EBNA-2
      supported enhanced HIV-1 replication as measured by accumulation of reverse
      transcriptase activity and syncytium induction. This provides direct evidence
      that EBV infection can enhance HIV-1 replication in T cells. Whether this in
      vitro phenomenon contributes to disease progression in vivo remains to be
      determined.

PMID- 9007202
TI  - trans-Activation of the HIV type 1 promoter by 7,8-dihydroneopterin in vitro.
AB  - Infection with human immunodeficiency virus type 1 and 2 is associated with
      elevated concentrations of neopterin, released in large quantities by human
      macrophages on stimulation with interferon gamma. Evidence has suggested a
      potential role of neopterin derivatives in oxygen radical-mediated processes.
      Here we show that the redox-sensitive transcription factors AP-1 and NF-kappaB
      are activated by 7,8-dihydroneopterin, either directly (AP-1), or by the
      synergistic action with tumor necrosis factor alpha (NF-kappaB). We could further
      demonstrate that 7,8-dihydroneopterin enhances HIV-1 expression as shown in
      transient transfection assays using HIV-1 CAT promoter-reporter gene constructs.
      In sera of HIV+ patients 7,8-dihydroneopterin significantly correlated with
      neopterin and HIV-1 p24 antigen. On the basis of our data we therefore assume
      that 7,8-dihydroneopterin might augment progression to higher stages of HIV
      associated disease.

PMID- 9007203
TI  - Potent inhibition of replication of primary HIV type 1 isolates in peripheral
      blood lymphocytes by negatively charged human serum albumins.
AB  - We previously reported the antiviral capacity of human serum albumin (HSA), which
      was modified by the introduction of a single (Suc-HSA) or two carboxylic groups
      (Aco-HSA) per lysine residue, yielding strongly negatively charged polypeptides.
      Here we report the antiviral effect of these modified HSAs on replication of
      primary HIV-1 isolates that differed with respect to syncytium-inducing (SI)
      capacity and cell tropism. Both Suc-HSA and Aco-HSA potently inhibited
      replication of primary HIV-1 variants, independent of the SI capacity of the HIV
      1 variant, with IC50 values in the range of 50 to 187 microg/ml. The inhibition
      of the formation of syncytia and the absence of proviral DNA products in cells
      inoculated with HIV-1 in the presence of Suc-HSA or Aco-HSA pointed to
      interference at an early level in the virus replication cycle. The inhibitory
      capacity of Suc-HSA and Aco-HSA on primary HIV-1 variants suggests that these
      agents are potential candidates for use in antiviral therapy in HIV-infected
      individuals.

PMID- 9007204
TI  - Cell type-dependent effect of sodium valproate on human immunodeficiency virus
      type 1 replication in vitro.
AB  - Sodium valproate (VPA), a simple branched-chain fatty acid that has
      anticonvulsant activity and is used in the treatment of many forms of epilepsy,
      has been reported to stimulate human immunodeficiency virus (HIV) type 1
      replication in acutely infected CEM and chronically infected U1 cells (Chemico
      Biological Interactions 1994;91:111-121). When attempting to reproduce and extend
      these findings, we confirmed that VPA is able to stimulate HIV-1(IIIB)
      replication in acutely infected CEM and C8166 T lymphocytic cell lines and
      chronically infected ACH-2 and U937/IIIB/LAI cells in a concentration-dependent
      manner. The stimulatory effect of VPA on HIV replication in CEM cells was not
      increased by pretreatment of the cells with VPA for 24 hr before infection.
      However, we could not detect any stimulatory effect of VPA on HIV-1(IIIB)
      replication in acutely infected peripheral blood mononuclear cells (PBMCs), MT-4,
      MT-2, HUT-78, and MOLT-4 (clone 8) cells and in chronically infected HUT
      78/IIIB/LAI cells. The stimulatory effect by VPA under certain conditions (see
      above) may be ascribed to an enhanced HIV transcription, as VPA was found to
      enhance the HIV long terminal repeat (LTR)-directed expression of beta
      galactosidase in transiently transfected HLtat, P4, and COS7 cells. VPA did not
      enhance beta-galactoside expression mediated by the cytomegalovirus (CMV)
      promoter. VPA did not affect HIV-induced syncytium formation. Nor had VPA any
      direct inactivating effect on HIV.

PMID- 9007205
TI  - Stavudine selectively induces apoptosis in HIV type 1-infected cells.
AB  - We evaluated the cytotoxic effects of various human immunodeficiency virus (HIV
      1) reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine,
      stavudine, and nevirapine) on HIV-1-infected and uninfected T cell lines. Among
      the compounds, only stavudine (not the others) proved to be more cytotoxic to
      MOLT-4/IIIB cells (MOLT-4 cells chronically infected with HIV-1) than to
      uninfected MOLT-4 cells. Its 50% cytotoxic concentrations were 59.8 and 2.2
      microM for MOLT-4 and MOLT-4/IIIB cells, respectively. Stavudine was also more
      cytotoxic to CEM/ROD (CEM cells chronically infected with HIV type 2) than to
      uninfected CEM cells. Microscopic analysis revealed that stavudine induced
      apoptosis in MOLT-4/IIIB cells. Apparent chromatin condensation in the nucleus
      was observed by electron microscopy. Furthermore, a DNA fragmentation ladder was
      detected by agarose gel electrophoresis. Addition of thymidine to the culture
      medium could rescue the cells from stavudine-induced apoptosis. The expression of
      anti-apoptotic protein Bcl-2 was partially downregulated in MOLT-4/IIIB cells
      after treatment with stavudine. This downregulation was not identified in MOLT-4
      cells. These results indicate that stavudine selectively induces apoptosis in HIV
      1-infected T cells and may have potential as a novel strategy for effective
      chemotherapy of the acquired immune deficiency syndrome (AIDS).

PMID- 9007207
TI  - Computer-assisted imaging of embryonic and fetal development. Background,
      recommendations and overview.

PMID- 9007208
TI  - Current and future interests of National Institute of Child Health and Human
      Development.

PMID- 9007206
TI  - HIV type 1 env gene diversity detected in Taiwan.

PMID- 9007209
TI  - Serial sections and human embryology: a new research initiative.
AB  - The author provides an historical and current view of the work of the Human
      Developmental Anatomy Center of the National Museum of Health and Medicine of the
      Armed Forces Institute of Pathology in Washington, DC. A project to create and
      disseminate electronic images from the extensive holdings, as presented at a 1994
      National Institutes of Health conference, is described.

PMID- 9007210
TI  - The visible embryo project: embedded program objects for knowledge access,
      creation and management through the World Wide Web.
AB  - We have designed a prototype knowledge management online environment for the
      biomedical sciences which integrates access to online representations of the
      scientific literature, bibliographic databases, high-performance visualization
      technologies, large-scale scientific databases, and tools for authoring new
      generation scientific publications. This system will provide widespread access to
      its resources by using the World Wide Web for its underlying architecture. This
      system expands upon our Weblet Interactive Remote Visualization (IRV) server
      technology to produce a set of dedicated Internet "visualization servers" which
      provide interactive control of real-time visualizations from the Visible Embryo
      Project database from within Web pages viewed with our WebRouser software
      package. This system will be used to develop a set of prototype applications for
      both online education of medical students in developmental anatomy and for an
      interactive patient education system for expectant parents. We recognize that
      knowledge represented by these national resource databases is not static,
      therefore it is essential to include tools for both the creation of new "compound
      documents" which incorporate embedded objects, as well as for managing the peer
      review of scholarly publications, in order to ensure the integrity of new
      knowledge as it is added to these databases in the future. We have therefore
      begun to design integrated tools for our system which facilitate both the
      creation of and the validation of new generations of scientific knowledge.

PMID- 9007211
TI  - An Internet atlas of mouse development.
AB  - A prototype two- and three-dimensional color atlas of mouse development is
      described. The prototype has been developed using two embryos, a 13.5 d normal
      mouse embryo and a PATCH mutant embryo of the same age. Serial sections of the
      embryos, with an external registration marker system, introduced into the
      paraffin embedding process, were prepared by standard histological methods. For
      the 2D atlas, color images were digitized from 100 consecutive sections of the
      normal embryo. For the 3D atlas, 300 gray scale images digitized from the mutant
      embryo were conformally warped and reconstructed into a 3D volume dataset. The
      external fiducial system facilitated the three-dimensional reconstruction by
      providing accurate registration of consecutive images and also allowed for
      precise spatial calibration and the correction for warping artifacts. The
      atlases, with their associated anatomical knowledge base, will be integrated into
      a multimedia on-line information resource via the Internet's World Wide Web (WWW)
      using an enhanced (patent pending, Eolas Technologies) version of the Mosaic WWW
      browser program from the National Center for Supercomputer Applications. These
      programs will provide research biologists with a set of advanced tools to analyze
      normal and abnormal development.

PMID- 9007212
TI  - Examination of three-dimensional movements in human embryos using computer
      imaging technology.
AB  - This paper describes the use of computer imaging technology to study in three
      dimensions the dynamics of differentiations in human embryos. Three-dimensional
      computer reconstruction technology was used to build a series of models of the
      brain/face and the ear region from fixed, serially sectioned embryos at
      representative stages. When certain principles are followed each model can be
      equated to one frame on a motion picture film. The dynamics of differentiation
      are then revealed as changes in size, shape and position (growth movements) of
      multiple structures as they build the definitive arrangement.

PMID- 9007213
TI  - The fetal imaging workstation demonstration project.
AB  - Congenital birth defects are a leading cause of infant mortality. Early detection
      of fetal anomalies by prenatal ultrasound may improve clinical outcome in
      selected cases. However, many training programs are hindered by curriculum
      weaknesses which include: (1) limited physician exposure to ultrasound anomalies;
      (2) inadequate postnatal correlation with prenatal findings; (3) constraints
      imposed by static images for ultrasound training; and (4) difficulty with
      understanding complex three-dimensional anatomy. The Fetal Imaging Workstation
      Demonstration Project addresses these problems by illustrating how computers can
      supplement traditional prenatal ultrasound training through interactive
      multimedia. The project uses a laserdisc library of ultrasound video images as
      source material for a variety of interactive software tutorials. An educational
      testing module has been developed that can evaluate diagnostic skills through
      simulated ultrasound studies provided by the laserdisc library. An interactive
      three-dimensional fetal heart model also provides a new way for physicians to
      better understand their two-dimensional ultrasound studies. A survey suggests
      that this prototype has been widely accepted by housestaff physicians and that
      there is a perceived need for this supplementary training. Future work will
      address the educational effectiveness of these materials and will consider cost
      effective ways to disseminate the software for other institutions. However,
      future development must be implemented against a background of rapidly emerging
      technologies involving faster computers, digital video, and virtual reality
      applications.

PMID- 9007214
TI  - Magnetic resonance imaging methods for study of human brain function and their
      application at high magnetic field.
AB  - Magnetic resonance imaging (MRI) sequences are finding a new application in the
      study of human brain function by monitoring localized changes in signal intensity
      which accompany neuronal activity. These sequences can be sensitized to changes
      in cerebral blood volume, cerebral blood flow, and blood oxygenation, all of
      which reflect aspects of neuronal activity in the brain. Many of these
      experiments benefit from being implemented at a higher magnetic field strength
      than conventional MRI. An overview of these techniques is presented, and examples
      of their use are given.

PMID- 9007215
TI  - Magnetic resonance microscopy of embryos.
AB  - We demonstrate that magnetic resonance (MR) microscopy provides a mechanism to
      investigate normal and abnormal developmental anatomy in a non-destructive and
      distortion-free manner. Techniques for the fixation, embedding, perfusion and
      image acquisition of embryos between 3 and 30 mm crown rump length are described.
      We describe the perfusion of a contrast agent to enhance images of the developing
      embryonic vasculature. Data are acquired as three-dimensional isotropic arrays
      which permit images to be reformatted retrospectively in any plane. The data are
      available for archiving, distributing and for post-acquisition manipulations. MR
      microscopy is a fast technique for producing three-dimensional reconstructions
      and is free from registration and sectioning artifacts.

PMID- 9007216
TI  - Computer-assisted imaging of the fetus with magnetic resonance imaging.
AB  - The purpose of this paper is to review the use of magnetic resonance imaging
      (MRI) of the fetus and to propose future techniques and applications.
      Institutional review board approved MR images of the fetus were acquired in 66
      patients with sonographically suspected fetal abnormalities. Axial, coronal, and
      sagittal short TR, short TE images were obtained. In addition, 12 studies were
      performed with rapid scans requiring 700-1200 ms using either GRASS or Spoiled
      GRASS techniques. Sequential studies demonstrating fetal motion were also
      performed. Three studies with 3D IR prepped GRASS were performed. These allowed
      for orthogonal and non-orthogonal reformatted views and 3D display. Normal fetal
      structures were shown with MRI, including brain, heart, liver, stomach,
      intestines, and bladder. Gross fetal anomalies could generally be demonstrated
      with MRI. MRI may give additional information to that of sonography in fetal
      anomalies, particularly those involving the central nervous system, and in the
      detection of fat, blood, and meconium. MRI of the fetus can demonstrate normal
      and abnormal structures. Newer techniques with faster imaging will allow for
      greater possibility of computer assisted manipulation of data.

PMID- 9007217
TI  - HER-2/neu signal transduction in human breast and ovarian cancer.
AB  - The HER-2/neu proto-oncogene encodes a 185 kDa transmembrane receptor tyrosine
      kinase with significant sequence homology to other members of the class I
      receptor tyrosine kinase family. The HER-2/neu gene is amplified and/or
      overexpressed in 25%-30% of human breast and ovarian cancers, and overexpression
      of the receptor is associated with poor prognosis. Tyrosine phosphorylation and
      activation of the HER-2 receptor lead to activation of specific signal
      transduction pathways in breast and ovarian cancer cells, including the ras/MAP
      kinase cascade, phosphatidylinositol 3-kinase, and phospholipase C-gamma. HER
      2/neu signal transduction pathways ultimately converge on the cell nucleus, where
      the expression of diverse genes is induced after activation of the receptor. A
      more complete understanding of HER-2/neu signal transduction pathways may allow
      the development of specific therapeutics for the treatment of those human breast
      and ovarian cancers containing this alteration.

PMID- 9007218
TI  - The use of mobilized peripheral blood stem cells from normal donors for
      allografting.
AB  - Peripheral blood stem cells (PBSCs) are gaining increasing acceptance as an
      alternative to bone-marrow (BM)-derived stem cells for allografting. Although
      scarce under steady-state conditions, CD34+ progenitor cells can be effectively
      mobilized into the peripheral blood (PB) in the vast majority of normal donors
      with a brief (3-4 days) course of recombinant human (rHu)G-CSF. Those cytokine
      peripheralized progenitor cells and, among them, pluripotent stem cells, are
      collected by apheresis in sufficient amounts to achieve complete and permanent
      alloengraftment after myeloablative treatment in patients with primarily
      malignant hematologic disorders. The short-term tolerability profile of PBSC
      mobilization and apheresis in normal donors appears to be acceptable, although
      continued monitoring is necessary to ensure long-term safety. When compared with
      BM progenitor cells, mobilized PBSCs seem to exhibit a more primitive phenotype
      and a different clonogenic potential. The impact of factors affecting the
      efficiency of PBSC mobilization, such as rHuG-CSF dose, duration of cytokine
      treatment, and, to a lesser extent, donor age is now being recognized. Potential
      ways to optimize and possibly "engineer" PBSC collection, such as the use of
      cytokine/chemokine combinations (e.g., thrombopoietin, stem cell factor, etc.)
      and monoclonal antibodies directed against integrin receptors on CD34+ progenitor
      cells, are now being explored as well. In the clinical setting, engraftment after
      PBSC allografting is rapid and probably faster than after BM allografting. PBSC
      allografting seems to be associated with an incidence and severity of acute graft
      versus-host disease (GVHD) comparable to the ones observed after BM allografting,
      although the incidence of chronic GVHD after allogeneic PBSC transplantation is
      still controversial. The infusion of a larger number of lymphoid cells appears to
      translate into a more rapid immunologic recovery and may lead to an enhanced
      graft-versus-leukemia effect. The collection of large numbers of mobilized PBSCs
      should provide ample opportunities for graft engineering and gene therapy. PBSCs
      may eventually replace, at least in part, BM as the preferred source of stem
      cells for both auto- and allotransplantation.

PMID- 9007219
TI  - Effects of recombinant human thrombopoietin alone and in combination with
      erythropoietin and early-acting cytokines on human mobilized purified CD34+
      progenitor cells cultured in serum-depleted medium.
AB  - The effects of recombinant thrombopoietin (TPO) alone and in combination with
      erythropoietin (EPO) and early-acting cytokines such as interleukin 3 (IL-3),
      stem cell factor (SCF) and GM-CSF on highly purified mobilized human CD34+
      progenitor cells were studied in a serum-depleted culture system. Eight
      leukapheresis samples were cultured for seven days and analyzed; aliquots were
      replated and re-evaluated on day 12. Three-color flow cytometry was used together
      with morphologic analysis to determine proliferation and megakaryocytic or
      erythroid maturation. TPO alone was sufficient for cell survival and
      proliferation in serum-depleted medium. In the absence of other growth factors,
      almost all CD34+ cells differentiated along the megakaryocytic pathway within 12
      days. Concomitantly, the progenitor cells gradually acquired the morphologic
      features of mature megakaryocytes. After exposure to TPO for one week, 50% of the
      cells still expressed CD34; by day 12 the remaining CD34+ cells (11%) were all
      coexpressing CD41. TPO alone did not support proliferation of glycophorin-A
      positive cells. The addition of TPO to early-acting cytokines (EPO, GM-CSF, SCF
      and/or IL-3) not only increased the overall megakaryocyte expansion, but also
      generated a different maturation pattern of the CD41+ megakaryocyte progenitors.
      It further doubled the number of erythroid cells and c-kit+ cells in the second
      week of culture. Interestingly, the overall number of CD34+ cells was increased
      about fivefold when TPO was added to the early-acting cytokines, with a marked
      expansion of the CD34+/CD41+ and CD34+/CD117+ subpopulations. TPO can augment the
      pool of committed progenitors, thereby increasing the number of its own target
      cells and the number of EPO-responsive cells. These properties make TPO an
      interesting cytokine for the ex vivo expansion of human progenitor cells.

PMID- 9007221
TI  - An analysis of the effects of combined treatment with rmGM-CSF and PEG-rHuMGDF in
      murine bone marrow transplant recipients.
AB  - We have studied the potential of combination growth factor treatment with GM-CSF
      and megakaryocyte growth and development factor (MGDF) to stimulate hematopoietic
      recovery in mice following bone marrow transplantation. More rapid recovery of
      neutrophils occurred in mice treated with recombinant murine (rm)GM-CSF plus
      pegylated recombinant human (PEG-rHu)MGDF than carrier treated controls, however
      this recovery was equivalent to the effect of treatment with rmGM-CSF alone. PEG
      rHuMGDF stimulated a more rapid recovery of platelets with no effect on
      neutrophil recovery. At the two tested doses of rmGM-CSF (72 and 200
      microg/kg/day) the platelet recovery was inferior to that in carrier treated
      mice. Also, the addition of rmGM-CSF to PEG-rHuMGDF had a dose-related negative
      impact on platelet recovery compared to PEG-rHuMGDF alone. These data suggest
      that the use of combination therapy in some clinical indications may lead to
      unexpected results. Furthermore, careful dosage studies may be necessary to
      identify the full potential of combined growth factors to obtain additive or
      synergistic effects on multilineage hematopoietic reconstitution in vivo.

PMID- 9007220
TI  - Mpl ligand (MGDF) alone and in combination with stem cell factor (SCF) promotes
      proliferation and survival of human megakaryocyte, erythroid and
      granulocyte/macrophage progenitors.
AB  - We examined cytokine-stimulated proliferation and survival of human megakaryocyte
      progenitor cells. We used a reliable, immunoenzymatic method of labeling CD41a-,
      CD42b-stained megakaryocytes in intact agar cultures to specifically identify and
      enumerate all megakaryocyte-containing colonies. We examined a previously defined
      population of cells enriched for megakaryocyte progenitors that coexpress CD34
      and the megakaryocyte/platelet marker CD61. These CD34+61+ cells displayed
      clonogenicity of approximately 30% and contained myeloid, erythroid and
      megakaryocyte progenitor cells. With single CD34+61+ cells, megakaryocyte growth
      and development factor ([MGDF], also known as mpl-ligand or thrombopoietin)
      stimulated 9% of cells to complete their first cell division by day 2 (versus 21%
      with stem cell factor [SCF], or 13% with interleukin 3 alone). MGDF showed an
      additive effect with SCF and interleukin 3 to increase this number at least
      twofold. In purified CD34+61+ cells, MGDF stimulated the survival of
      megakaryocyte-colony forming cells (CFC) when addition of other proliferative
      factors was delayed for 5, 10 and 15 days (all p < 0.0001 versus saline control).
      MGDF also promoted survival of BFU-E and granulocyte-macrophage-CFC for at least
      10 days (p < or = 0.0013 and p < or = 0.0362, respectively). SCF alone prolonged
      survival of CD34+61+ progenitor cells, however, MGDF + SCF was significantly more
      active. Whereas the action of MGDF on megakaryocyte-CFC was evident both in
      stimulating proliferation and survival, its ability to promote survival was
      between two- and fivefold greater than its action to stimulate proliferation.
      Thus MGDF alone, and in combination with SCF, was active in promoting the
      survival and proliferation of human progenitor cells of multiple hemopoietic
      lineages.

PMID- 9007223
TI  - Distinct qualitative differences between normal and abnormal hemopoietic stem
      cells in vivo and in vitro.
AB  - The transplantation of partially purified hemopoietic stem cells (HSCs) plus the
      engraftment of bone from autoimmune-prone mice ((NZW x BXSB)F1 (W/BF1) mice)
      induces autoimmune diseases in major histocompatibility complex (MHC)
      incompatible normal C3H/HeN mice. In contrast, W/BF1 mice die of infection or
      anemia within three weeks due to a failure in hemopoietic reconstitution when the
      mice receive partially purified HSCs plus bones from normal C3H/HeN mice,
      although they survive more than a year without showing any symptoms of autoimmune
      diseases when they receive T cell-depleted bone marrow cells (without bone
      grafts) from normal mice. This finding suggests that abnormal HSCs can
      proliferate even in MHC-incompatible microenvironments, while normal HSCs cannot.
      This is confirmed by spleen colony-forming assays (CFU-S) on day 12, using
      pluripotent HSCs (P-HSCs). The P-HSCs of old (> 4 mo) W/BF1 mice (after the
      development of autoimmune diseases) form high CFU-S counts on day 12 even in the
      allogeneic C3H environment, although the P-HSCs of normal mice form high CFU-S
      counts only in the MHC-compatible environments. In addition, abnormal P-HSCs of
      autoimmune-prone mice can proliferate in vitro in collaboration with MHC
      incompatible stromal cells, although normal HSCs do so in collaboration with MHC
      compatible stromal cells, but not MHC-incompatible stromal cells. These findings
      indicate that abnormal P-HSCs are more "resilient" than normal P-HSCs.

PMID- 9007222
TI  - Leukemia inhibitory factor induces in vivo expansion of bone marrow progenitor
      cells that accelerate hematopoietic reconstitution but do not enhance
      radioprotection in lethally irradiated mice.
AB  - Leukemia inhibitory factor (LIF) is a pleiotropic cytokine with distinct
      hematopoietic activities. In vivo treatment of mice with recombinant murine LIF
      induces thrombocytosis and increases the number of hematopoietic progenitor cells
      (HPCs) in spleen and bone marrow (BM). In this study, we applied LIF to expand
      HPCs in vivo prior to syngeneic BM transplantation. BALB/c donor mice were
      treated with recombinant human LIF at a dose of 2.5 microg/day s.c. for seven
      days. This resulted in a 1.6-fold increment in platelet counts from 941 to 1,470
      x 10(9)/l (mean, n = 20). Mean spleen weight increased from 120 mg to 160 mg (n =
      5). The total numbers of HPCs in the spleen as well as in the BM, as assessed in
      a CFU-GM (colony forming unit-granulocyte-macrophage) assay, were significantly
      higher in LIF-treated donors than in saline-treated controls (30.1 +/- 14.5
      versus 7.4 +/- 5.3 x 10(3) per spleen; mean +/- SD, n = 22,p < 0.001 and 74.4 +/-
      17.1 versus 55.3 +/- 16.1 x 10(3) per femur, p < 0.001). Recipient mice were
      lethally (8.5 Gy) irradiated and transplanted with 3 x 10(5) BM cells derived
      from LIF- or saline-treated donors. Hematopoietic reconstitution was monitored by
      tail bleeding at three-day intervals. Platelet and WBC nadir counts in control
      animals were reached at day 9 (31 +/- 25 x 10(9)/l for platelets and 0.40 +/-
      0.10 x 10(9)/l for WBC; mean +/- SD, n = 29 per treatment group); in animals
      transplanted with LIF-treated BM cells, these counts were 44 +/- 25 x 10(9)/l for
      platelets, p < 0.05 and 0.60 +/- 0.38 x 10(9)/l for WBC, p < 0.01. In addition,
      platelet reconstitution was faster in recipients of LIF-treated BM cells (226 +/-
      118 versus 126 +/- 62 x 10(9)/l at day 12 and 633 +/- 174 versus 434 +/- 180 x
      10(9)/l at day 15, p < 0.001). Similarly, the reconstitution of WBC was also
      significantly enhanced. The radioprotection rate of lethally irradiated
      recipients with increasing cell doses of BM cells derived from LIF-treated donors
      was higher at all cell doses tested then of control animals, but did not reach
      statistical significance. These results show that in vivo treatment with LIF
      expands the number of committed progenitor cells and BM repopulating cells that
      accelerate short-term hematopoietic reconstitution without increasing
      radioprotection. Our data do not support a major role for LIF as a single factor
      inducing expansion of hematopoietic stem cells in vivo.

PMID- 9007224
TI  - Raf-1 protein is required for growth factor-induced proliferation of primitive
      hematopoietic progenitors stimulated with synergistic combinations of cytokines.
AB  - Raf-1 is a serine/threonine kinase that has been identified as a component of
      growth factor-activated signal transduction pathways, and is required for growth
      factor-induced proliferation of leukemic cell lines and colony formation of
      hematopoietic progenitors stimulated with single colony-stimulating factors,
      which promote the growth of committed hematopoietic progenitor cells. However, it
      is known that the most primitive progenitors in the bone marrow require
      stimulation with multiple cytokines to promote cell growth. We have determined
      that c-raf antisense oligonucleotides inhibit the growth of murine lineage
      negative progenitors stimulated with two-, three- and four-factor combinations of
      growth factors, including GM-CSF + interleukin (IL)- 1, IL-3 + steel factor
      (SLF), IL-3 + IL-11 + SLF and IL-3 + IL-11 + SLF + G-CSF. In addition, c-raf
      antisense oligonucleotides inhibit the synergistic response of the MO7e human
      progenitor cell line induced to proliferate with IL-3 + SLF (99%) or GM-CSF + SLF
      (99%). In contrast, c-raf antisense oligonucleotides only partially inhibited day
      14 colony formation of CD34+ human progenitors stimulated with IL-3 + SLF (50%)
      or GM-CSF + SLF (55%) but completely inhibited day 7 colony formation. However,
      pulsing CD34+ cells with additional oligonucleotides on day 7 of the colony assay
      further inhibited day 14 colony formation (70%-80%). Furthermore, a comparison of
      the effect of c-raf antisense oligonucleotides on the synergistic response of
      normal human fetal liver cells in [3H]thymidine incorporation assays and colony
      assays showed strong inhibition in short-term proliferation assays and partial
      inhibition in 14-day colony assays. Taken together, these results demonstrate
      that partial inhibition of colony formation of primitive human progenitors
      stimulated with multiple growth factors is a result of the length (14 days) of
      the human colony assay and does not represent a differential requirement of
      primitive progenitors for Raf-1. Thus Raf-1 is required for the proliferation and
      differentiation of primitive hematopoietic progenitor cells stimulated with
      synergistic combinations of cytokines.

PMID- 9007225
TI  - Functional differences between subpopulations of mobilized peripheral blood
      derived CD34+ cells expressing different levels of HLA-DR, CD33, CD38 and c-kit
      antigens.
AB  - We have investigated the functional characteristics of peripheral blood-derived
      CD34+ cells mobilized by a combination of chemotherapy and G-CSF (mobilized
      peripheral blood-derived [MPB] CD34+ cells). In this study, subpopulations of MPB
      CD34+ cells have been directly compared in clonal cultures, long-term cultures
      with bone marrow (BM) stromal cells, and single-cell cultures. MPB CD34+ cells
      could be subdivided by expression levels of HLA-DR (DR), CD38, CD33 and c-kit
      antigens. The majority of MPB CD34+ cells expressed DR and CD38 antigens. In
      contrast, approximately 60% and 20% of the MPB CD34+ cells expressed CD33 and c
      kit antigens, respectively. Interestingly, MPB CD34+ cells can be subdivided into
      three fractions which express high, low or negative levels of c-kit receptor. All
      types of committed progenitors were observed in populations of CD34+DR+, CD34+DR
      , CD34+CD33-, CD34+CD38+ and CD34+ c-kit(low) cells. Colony forming unit
      granulocyte/macrophage was highly enriched in the population of CD34+CD33+ cells,
      whereas BFU-E was highly enriched in the population of CD34+ c-kit(high) cells.
      In the population of CD34+CD38- cells, however, a few myeloid progenitors were
      detected. In addition, limiting dilution analyses clearly showed that the long
      term culture-initiating cell (LTC-IC) is enriched in the populations of CD34+DR-,
      CD34+CD33- and CD34+c-kit-(or low) cells, but very few in CD34+ c-kit(high)
      cells, and that CD38 antigen is not a useful marker for the enrichment of LTC-IC
      derived from MPB CD34+ cells. Moreover, single cell clone sorting experiments
      clearly demonstrated the functional differences between CD34+CD38+ and CD34+CD38-
      cells as well as CD34+ cells expressing different levels of c-kit receptor. Our
      results suggest that an immunophenotype of LTC-IC is different between BM-, cord
      blood- and MPB-derived CD34+ cells and that primitive and committed progenitors
      existing in these sources may be functionally different.

PMID- 9007226
TI  - The identification of genes with unique and essential functions in the
      development of the zebrafish, Danio rerio.
AB  - In a large-scale screen, we isolated mutants displaying a specific visible
      phenotype in embryos or early larvae of the zebrafish, Danio rerio. Males were
      mutagenized with ethylnitrosourea (ENU) and F2 families of single pair matings
      between sibling F1 fish, heterozygous for a mutagenized genome, were raised. Egg
      lays were obtained from several crosses between F2 siblings, resulting in scoring
      of 3857 mutagenized genomes. F3 progeny were scored at the second, third and
      sixth day of development, using a stereomicroscope. In a subsequent screen, fixed
      embryos were analyzed for correct retinotectal projection. A total of 4264
      mutants were identified. Two thirds of the mutants displaying rather general
      abnormalities were eventually discarded. We kept and characterized 1163 mutants.
      In complementation crosses performed between mutants with similar phenotypes, 894
      mutants have been assigned to 372 genes. The average allele frequency is 2.4. We
      identified genes involved in early development, notochord, brain, spinal cord,
      somites, muscles, heart, circulation, blood, skin, fin, eye, otic vesicle, jaw
      and branchial arches, pigment pattern, pigment formation, gut, liver, motility
      and touch response. Our collection contains alleles of almost all previously
      described zebrafish mutants. From the allele frequencies and other considerations
      we estimate that the 372 genes defined by the mutants probably represent more
      than half of all genes that could have been discovered using the criteria of our
      screen. Here we give an overview of the spectrum of mutant phenotypes obtained,
      and discuss the limits and the potentials of a genetic saturation screen in the
      zebrafish.

PMID- 9007227
TI  - A genetic screen for mutations affecting embryogenesis in zebrafish.
AB  - Systematic genome-wide mutagenesis screens for embryonic phenotypes have been
      instrumental in the understanding of invertebrate and plant development. Here, we
      report the results from the first application of such a large-scale genetic
      screening to vertebrate development. Male zebrafish were mutagenized with N-ethyl
      N-nitrosourea to induce mutations in spermatogonial cells at an average specific
      locus rate of one in 651 mutagenized genomes. Mutations were transmitted to the
      F1 generation, and 2205 F2 families were raised. F3 embryos from sibling crosses
      within the F2 families were screened for developmental abnormalities. A total of
      2337 mutagenized genomes were analyzed, and 2383 mutations resulting in abnormal
      embryonic and early larval phenotypes were identified. The phenotypes of 695
      mutants indicated involvement of the identified loci in specific aspects of
      embryogenesis. These mutations were maintained for further characterization and
      were classified into categories according to their phenotypes. The analyses and
      genetic complementation of mutations from several categories are reported in
      separate manuscripts. Mutations affecting pigmentation, motility, muscle and body
      shape have not been extensively analyzed and are listed here. A total of 331
      mutations were tested for allelism within their respective categories. This
      defined 220 genetic loci with on average 1.5 alleles per locus. For about two
      thirds of all loci only one allele was isolated. Therefore it is not possible to
      give a reliable estimate on the degree of saturation reached in our screen;
      however, the number of genes that can mutate to visible embryonic and early
      larval phenotypes in zebrafish is expected to be several-fold larger than the one
      for which we have observed mutant alleles during the screen. This screen
      demonstrates that mutations affecting a variety of developmental processes can be
      efficiently recovered from zebrafish.

PMID- 9007228
TI  - The zebrafish epiboly mutants.
AB  - Epiboly, the enveloping of the yolk cell by the blastoderm, is the first
      zebrafish morphogenetic movement. We isolated four mutations that affect epiboly:
      half baked, avalanche, lawine and weg. Homozygous mutant embryos arrest the
      vegetal progress of the deep cells of the blastoderm; only the yolk syncytial
      layer of the yolk cell and the enveloping layer of the blastoderm reach the
      vegetal pole of the embryo. The mutations half baked, avalanche and lawine
      produce a novel dominant effect, termed a zygotic-maternal dominant effect:
      heterozygous embryos produced from heterozygous females slow down epiboly and
      accumulate detached cells over the neural tube; a small fraction of these mutant
      individuals are viable. Heterozygous embryos produced from heterozygous males
      crossed to homozygous wild-type females complete epiboly normally and are
      completely viable. Additionally, embryos heterozygous for half baked have an
      enlarged hatching gland, a partial dominant phenotype. The phenotypes of these
      mutants demonstrate that, for the spreading of cells during epiboly, the movement
      of the deep cells of the blastoderm require the function of genes that are not
      necessary for the movement of the enveloping layer or the yolk cell. Furthermore,
      the dominant zygotic-maternal effect phenotypes illustrate the maternal and
      zygotic interplay of genes that orchestrate the early cell movements of the
      zebrafish.

PMID- 9007229
TI  - The zebrafish early arrest mutants.
AB  - This report describes mutants of the zebrafish having phenotypes causing a
      general arrest in early morphogenesis. These mutants identify a group of loci
      making up about 20% of the loci identified by mutants with visible morphological
      phenotypes within the first day of development. There are 12 Class I mutants,
      which fall into 5 complementation groups and have cells that lyse before
      morphological defects are observed. Mutants at three loci, speed bump, ogre and
      zombie, display abnormal nuclei. The 8 Class II mutants, which fall into 6
      complementation groups, arrest development before cell lysis is observed. These
      mutants seemingly stop development in the late segmentation stages, and maintain
      a body shape similar to a 20 hour embryo. Mutations in speed bump, ogre, zombie,
      specter, poltergeist and troll were tested for cell lethality by transplanting
      mutant cells into wild-type hosts. With poltergeist, transplanted mutant cells
      all survive. The remainder of the mutants tested were autonomously but
      conditionally lethal: mutant cells, most of which lyse, sometimes survive to
      become notochord, muscles, or, in rare cases, large neurons, all cell types which
      become postmitotic in the gastrula. Some of the genes of the early arrest group
      may be necessary for progression though the cell cycle; if so, the survival of
      early differentiating cells may be based on having their terminal mitosis before
      the zygotic requirement for these genes.

PMID- 9007230
TI  - Mutations affecting cell fates and cellular rearrangements during gastrulation in
      zebrafish.
AB  - One of the major challenges of developmental biology is understanding the
      inductive and morphogenetic processes that shape the vertebrate embryo. In a
      large-scale genetic screen for zygotic effect, embryonic lethal mutations in
      zebrafish we have identified 25 mutations that affect specification of cell fates
      and/or cellular rearrangements during gastrulation. These mutations define at
      least 14 complementation groups, four of which correspond to previously
      identified genes. Phenotypic analysis of the ten novel loci revealed three groups
      of mutations causing distinct effects on cell fates in the gastrula. One group
      comprises mutations that lead to deficiencies in dorsal mesodermal fates and
      affect central nervous system patterning. Mutations from the second group affect
      formation of ventroposterior embryonic structures. We suggest that mutations in
      these two groups identify genes necessary for the formation, maintenance or
      function of the dorsal organizer and the ventral signaling pathway, respectively.
      Mutations in the third group affect primarily cellular rearrangements during
      gastrulation and have complex effects on cell fates in the embryo. This group,
      and to some extent mutations from the first two groups, affect the major
      morphogenetic processes, epiboly, convergence and extension, and tail
      morphogenesis. These mutations provide an approach to understanding the genetic
      control of gastrulation in vertebrates.

PMID- 9007231
TI  - Genes establishing dorsoventral pattern formation in the zebrafish embryo: the
      ventral specifying genes.
AB  - We identified 6 genes that are essential for specifying ventral regions of the
      early zebrafish embryo. Mutations in these genes cause an expansion of structures
      normally derived from dorsal-lateral regions of the blastula at the expense of
      ventrally derived structures. A series of phenotypes of varied strengths is
      observed with different alleles of these mutants. The weakest phenotype is a
      reduction in the ventral tail fin, observed as a dominant phenotype of swirl,
      piggytail, and somitabun and a recessive phenotype of mini fin, lost-a-fin and
      some piggytail alleles. With increasing phenotypic strength, the blood and
      pronephric anlagen are also reduced or absent, while the paraxial mesoderm and
      anterior neuroectoderm is progressively expanded. In the strong phenotypes,
      displayed hy homozygous embryos of snailhouse, swirl and somitabun, the somites
      circle around the embryo and the midbrain region is expanded laterally. Several
      mutations in this group of genes are semidominant as well as recessive indicating
      a strong dosage sensitivity of the processes involved. Mutations in the piggytail
      gene display an unusual dominance that depends on both a maternal and zygotic
      heterozygous genotype, while somitabun is a fully penetrant dominant maternal
      effect mutation. The similar and overlapping phenotypes of mutants of the 6 genes
      identified suggest that they function in a common pathway, which begins in
      oogenesis, but also depends on factors provided after the onset of zygotic
      transcription, presumably during blastula stages. This pathway provides ventral
      positional information, counteracting the dorsalizing instructions of the
      organizer, which is localized in the dorsal shield.

PMID- 9007232
TI  - dino and mercedes, two genes regulating dorsal development in the zebrafish
      embryo.
AB  - We describe two genes, dino and mercedes, which are required for the organization
      of the zebrafish body plan. In dino mutant embryos, the tail is enlarged at the
      expense of the head and the anterior region of the trunk. The altered expression
      patterns of various marker genes reveal that, with the exception of the dorsal
      most marginal zone, all regions of the early dino mutant embryo acquire more
      ventral fates. These alterations are already apparent before the onset of
      gastrulation. mercedes mutant embryos show a similar but weaker phenotype,
      suggesting a role in the same patterning processes. The phenotypes suggests that
      dino and mercedes are required for the establishment of dorsal fates in both the
      marginal and the animal zone of the early gastrula embryo. Their function in the
      patterning of the ventrolateral mesoderm and the induction of the neuroectoderm
      is similar to the function of the Spemann organizer in the amphibian embryo.

PMID- 9007233
TI  - Mutations affecting the formation of the notochord in the zebrafish, Danio rerio.
AB  - In a large scale screen for mutants with defects in the embryonic development of
      the zebrafish we identified mutations in four genes,floating head (flh), momo
      (mom), no tail (ntl), and doc, that are required for early notochord formation.
      Mutations in flh and ntl have been described previously, while mom and doc are
      newly identified genes. Mutant mom embryos lack a notochord in the trunk, and
      trunk somites from the right and left side of the embryo fuse underneath the
      neural tube. In this respect mom appears similar to flh. In contrast, notochord
      precursor cells are present in both ntl and doc embryos. In order to gain a
      greater understanding of the phenotypes, we have analysed the expression of
      several axial mesoderm markers in mutant embryos of all four genes. In flh and
      mom, Ntl expression is normal in the germ ring and tailbud, while the expression
      of Ntl and other notochord markers in the axial mesodermal region is disrupted.
      Ntl expression is normal in doc embryos until early somitic stages, when there is
      a reduction in expression which is first seen in anterior regions of the embryo.
      This suggests a function for doc in the maintenance of ntl expression. Other
      notochord markers such as twist, sonic hedgehog and axial are not expressed in
      the axial mesoderm of ntl embryos, their expression parallels the expression of
      ntl in the axial mesoderm of mutant doc, flh and mom embryos, indicating that ntl
      is required for the expression of these markers. The role of doc in the
      expression of the notochord markers appears indirect via ntl. Floor plate
      formation is disrupted in most regions in flh and mom mutant embryos but is
      present in mutant ntl and doc embryos. In mutant embryos with strong ntl alleles
      the band of cells expressing floor plate markers is broadened. A similar
      broadening is also observed in the axial mesoderm underlying the floor plate of
      ntl embryos, suggesting a direct involvement of the notochord precursor cells in
      floor plate induction. Mutations in all of these four genes result in embryos
      lacking a horizontal myoseptum and muscle pioneer cells, both of which are
      thought to be induced by the notochord. These somite defects can be traced back
      to an impairment of the specification of the adaxial cells during early stages of
      development. Transplantation of wild-type cells into mutant doc embryos reveals
      that wild-type notochord cells are sufficient to induce horizontal myoseptum
      formation in the flanking mutant tissue. Thus doc, like flh and ntl, acts cell
      autonomously in the notochord. In addition to the four mutants with defects in
      early notochord formation, we have isolated 84 mutants, defining at least 15
      genes, with defects in later stages of notochord development. These are listed in
      an appendix to this study.

PMID- 9007234
TI  - Mutations affecting development of the notochord in zebrafish.
AB  - The notochord is critical for the normal development of vertebrate embryos. It
      serves both as the major skeletal element of the embryo and as a signaling source
      for the establishment of pattern within the neurectoderm, the paraxial mesoderm
      and other tissues. In a large-scale systematic screen of mutations affecting
      embryogenesis in zebrafish we identified 65 mutations that fall into 29
      complementation groups, each leading to a defect in the formation and/or
      maintenance of the notochord. These mutations produce phenotypic abnormalities at
      numerous stages of notochord development, thereby establishing a phenotypic
      pathway, which in turn suggests a genetic pathway for the development of the
      notochord. Perturbations within adjacent tissues in mutant embryos further
      indicate the importance of notochord-derived signals for patterning within the
      embryo and suggest that these mutations will yield additional insight into the
      cues that regulate these patterning processes.

PMID- 9007235
TI  - Mutations affecting development of the midline and general body shape during
      zebrafish embryogenesis.
AB  - Tissues of the dorsal midline of vertebrate embryos, such as notochord and floor
      plate, have been implicated in inductive interactions that pattern the neural
      tube and somites. In our screen for embryonic visible mutations in the zebrafish
      we found 113 mutations in more than 27 genes with altered body shape, often with
      additional defects in CNS development. We concentrated on a subgroup of mutations
      in ten genes (the midline-group) that cause defective development of the floor
      plate. By using floor plate markers, such as the signaling molecule sonic
      hedgehog, we show that the schmalspur (sur) gene is needed for early floor plate
      development, similar to one-eyed-pinhead (oep) and the previously described
      cyclops (cyc) gene. In contrast to oep and cyc, sur embryos show deletions of
      ventral CNS tissue restricted to the mid- and hindbrain, whereas the forebrain
      appears largely unaffected. In the underlying mesendodermal tissue of the head,
      sur is needed only for development of the posterior prechordal plate, whereas oep
      and cyc are required for both anterior and posterior prechordal plate
      development. Our analysis of sur mutants suggests that defects within the
      posterior prechordal plate may cause aberrant development of ventral CNS
      structures in the mid- and hindbrain. Later development of the floor plate is
      affected in mutant chameleon, you-too, sonic-you, iguana, detour, schmalhans and
      monorail embryos; these mutants often show additional defects in tissues that are
      known to depend on signals from notochord and floor plate. For example, sur, con
      and yot mutants show reduction of motor neurons; median deletions of brain tissue
      are seen in sur, con and yot embryos; and cyc, con, yot, igu and dtr mutants
      often show no or abnormal formation of the optic chiasm. We also find fusions of
      the ventral neurocranium for all midline mutants tested, which may reveal a
      hitherto unrecognized function of the midline in influencing differentiation of
      neural crest cells at their destination. As a working hypothesis, we propose that
      midline-group genes may act to maintain proper structure and inductive function
      of zebrafish midline tissues.

PMID- 9007236
TI  - Mutations affecting morphogenesis during gastrulation and tail formation in the
      zebrafish, Danio rerio.
AB  - We have identified several genes that are required for various morphogenetic
      processes during gastrulation and tail formation. Two genes are required in the
      anterior region of the body axis: one eyed pinhead (oep) and dirty nose (dns).oep
      mutant embryos are defective in prechordal plate formation and the specification
      of anterior and ventral structures of the central nervous system. In dns mutants,
      cells of the prechordal plate, such as the prospective hatching gland cells, fail
      to specify. Two genes are required for convergence and extension movements. In
      mutant trilobite embryos, extension movements on the dorsal side of the embryo
      are affected, whereas in the formerly described spadetail mutants, for which two
      new alleles have been isolated, convergent movements of ventrolateral cells to
      the dorsal side are blocked. Two genes are required for the development of the
      posterior end of the body axis. In pipetail mutants, the tailbud fails to move
      ventrally on the yolk sac after germ ring closure, and the tip of the tail fails
      to detach from the yolk tube. Mutants in kugelig (kgg) do not form the yolk tube
      at the posterior side of the yolk sac.

PMID- 9007237
TI  - Mutations affecting somite formation and patterning in the zebrafish, Danio
      rerio.
AB  - Somitogenesis is the basis of segmentation of the mesoderm in the trunk and tail
      of vertebrate embryos. Two groups of mutants with defects in this patterning
      process have been isolated in our screen for zygotic mutations affecting the
      embryonic development of the zebrafish (Danio rerio). In mutants of the first
      group, boundaries between individual somites are invisible early on, although the
      paraxial mesoderm is present. Later, irregular boundaries between somites are
      present. Mutations in fused somites (fss) and beamter (bea) affect all somites,
      whereas mutations in deadly seven (des), after eight (aei) and white tail (wit)
      only affect the more posterior somites. Mutants of all genes but wit are
      homozygous viable and fertile. Skeletal stainings and the expression pattern of
      myoD and snail1 suggest that anteroposterior patterning within individual somites
      is abnormal. In the second group of mutants, formation of the horizontal
      myoseptum, which separates the dorsal and ventral part of the myotome, is
      reduced. Six genes have been defined in this group (you-type genes). you-too
      mutants show the most severe phenotype; in these the adaxial cells, muscle
      pioneers and the primary motoneurons are affected, in addition to the horizontal
      myoseptum. The horizontal myoseptum is also missing in mutants that lack a
      notochord. The similarity of the somite phenotype in mutants lacking the
      notochord and in the you-type mutants suggests that the genes mutated in these
      two groups are involved in a signaling pathway from the notochord, important for
      patterning of the somites.

PMID- 9007238
TI  - Mutations affecting the development of the embryonic zebrafish brain.
AB  - In a large scale mutagenesis screen for embryonic mutants in zebrafish, we have
      identified 63 mutations in 24 loci affecting the morphogenesis of the zebrafish
      brain. The expression of marker genes and the integrity of the axonal scaffold
      have been studied to investigate abnormalities in regionalization, neurogenesis
      and axonogenesis in the brain. Mutants can be broadly classified into two groups,
      one affecting regionalization along the anterior-posterior or dorsal-ventral
      axis, and the other affecting general features of brain morphology. The first
      group includes one locus that is required to generate the anlage of the midbrain
      hindbrain boundary region at the beginning of somitogenesis. Four loci were
      identified that affect dorsal-ventral patterning of the brain, including the
      previously described cyclops locus. Mutant embryos of this class show a reduction
      of ventral neuroectodermal structures and variable fusion of the eyes. The second
      group includes a large class of mutations affecting the formation of brain
      ventricles. Analysis of this class reveals the requirement of a functional
      cardiovascular system for ventricle enlargement during embryogenesis. Mutations
      in one locus lead to the formation of supernumerary primary neurons, a phenotype
      reminiscent of neurogenic mutants in Drosophila. Other mutant phenotypes
      described here range from abnormalities in the fasciculation and outgrowth of
      axons to defects in the diameter of the neural tube. The identified loci
      establish the genetic foundation for a further analysis of the development of the
      zebrafish embryonic brain.

PMID- 9007240
TI  - Genes involved in forebrain development in the zebrafish, Danio rerio.
AB  - We identified four zebrafish mutants with defects in forebrain induction and
      patterning during embryogenesis. The four mutants define three genes: masterblind
      (mbl), silberblick (slb), and knollnase (kas). In mbl embryos, the anterior
      forebrain acquires posterior forebrain characteristics: anterior structures such
      as the eyes, olfactory placodes and the telencephalon are missing, whereas the
      epiphysis located in the posterior forebrain is expanded. In slb embryos, the
      extension of the embryonic axis is initially delayed and eventually followed by a
      partial fusion of the eyes. Finally, in kas embryos, separation of the
      telencephalic primordia is incomplete and dorsal midline cells fail to form a
      differentiated roof plate. Analysis of the mutant phenotypes indicates that we
      have identified genes essential for the specification of the anterior forebrain
      (mbl), positioning of the eyes (slb) and differentiation of the roof plate (kas).
      In an appendix to this study we list mutants showing alterations in the size of
      the eyes and abnormal differentiation of the lenses.

PMID- 9007239
TI  - Mutations in zebrafish genes affecting the formation of the boundary between
      midbrain and hindbrain.
AB  - Mutations in two genes affect the formation of the boundary between midbrain and
      hindbrain (MHB): no isthmus (noi) and acerebellar (ace). noi mutant embryos lack
      the MHB constriction, the cerebellum and optic tectum, as well as the pronephric
      duct. Analysis of noi mutant embryos with neuron-specific antibodies shows that
      the MHB region and the dorsal and ventral midbrain are absent or abnormal, but
      that the rostral hindbrain is unaffected with the exception of the cerebellum.
      Using markers that are expressed during its formation (eng, wnt1 and pax-b), we
      find that the MHB region is already misspecified in noi mutant embryos during
      late gastrulation. The tectum is initially present and later degenerates. The
      defect in ace mutant embryos is more restricted: MHB and cerebellum are absent,
      but a tectum is formed. Molecular organisation of the tectum and tegmentum is
      disturbed, however, since eng, wnt1 and pax-b marker gene expression is not
      maintained. We propose that noi and ace are required for development of the MHB
      region and of the adjacent mid- and hindbrain, which are thought to be patterned
      by the MHB region. Presence of pax-b RNA, and absence of pax-b protein, together
      with the observation of genetic linkage and the occurrence of a point mutation,
      show that noi mutations are located in the pax-b gene. pax-b is a vertebrate
      orthologue of the Drosophila gene paired, which is involved in a pathway of
      cellular interactions at the posterior compartment boundary in Drosophila. Our
      results confirm and extend a previous report, and show that at least one member
      of this conserved signalling pathway is required for formation of the boundary
      between midbrain and hindbrain in the zebrafish.

PMID- 9007241
TI  - Mutations affecting neurogenesis and brain morphology in the zebrafish, Danio
      rerio.
AB  - In a screen for embryonic mutants in the zebrafish a large number of mutants were
      isolated with abnormal brain morphology. We describe here 26 mutants in 13
      complementation groups that show abnormal development of large regions of the
      brain. Early neurogenesis is affected in white tail (wit). During segmentation
      stages, homozygous wit embryos display an irregularly formed neural keel,
      particularly in the hindbrain. Using a variety of molecular markers, a severe
      increase in the number of various early differentiating neurons can be
      demonstrated. In contrast, late differentiating neurons, radial glial cells and
      some nonneural cell types, such as the neural crest-derived melanoblasts, are
      much reduced. Somitogenesis appears delayed. In addition, very reduced numbers of
      melanophores are present posterior to the mid-trunk. The wit phenotype is
      reminiscent of neurogenic mutants in Drosophila, such as Notch or Delta. In
      mutant parachute (pac) embryos the general organization of the hindbrain is
      disturbed and many rounded cells accumulate loosely in the hindbrain and midbrain
      ventricles. Mutants in a group of 6 genes, snakehead(snk), natter (nat), otter
      (ott), fullbrain (ful), viper (vip) and white snake (wis) develop collapsed brain
      ventricles, before showing signs of general degeneration. atlantis (atl), big
      head (bid), wicked brain (win), scabland (sbd) and eisspalte (ele) mutants have
      different malformation of the brain folds. Some of them have transient
      phenotypes, and mutant individuals may grow up to adults.

PMID- 9007242
TI  - Mutations affecting neural survival in the zebrafish Danio rerio.
AB  - Programmed cell death is a prominent feature of normal animal development. During
      neurogenesis, naturally occurring cell death is a mechanism to eliminate neurons
      that fail to make appropriate connections. To prevent accidental cell death,
      mechanisms that trigger programmed cell death, as well as the genetic components
      of the cell death program, are tightly controlled. In a large-scale mutagenesis
      screen for embryonic lethal mutations in zebrafish Danio rerio we have found 481
      mutations with a neural degeneration phenotype. Here, we present 50 mutations
      that fall into two classes (termed spacehead and fala-like) that are
      characterized by two main features: first, they appear to affect cell survival
      primarily within the neuroectodermal lineages during somitogenesis, and second,
      they show an altered brain morphology at or before 28 hours of development.
      Evidence for the specificity of cell death within the central nervous system
      comes from visual inspection of dying cells and analysis of DNA fragmentation, a
      process associated with apoptotic cell death. In mutants, the level of dying
      cells is significantly increased in brain and spinal cord. Furthermore, at the
      end of somitogenesis, the cell count of radial glia and trigeminal neurons is
      reduced in some mutants of the spacehead class. A variety of neurodegenerative
      disorders in mouse and humans have been associated with abnormal levels of
      programmed cell death within the central nervous system. The mutations presented
      here might provide a genetic framework to aid in the understanding of the
      etiology of degenerative and physiological disorders within the CNS and the
      activation of inappropriate programmed cell death.

PMID- 9007243
TI  - Neural degeneration mutants in the zebrafish, Danio rerio.
AB  - Forty zebrafish mutants with localized or general neural degeneration are
      described. The onset and duration of degeneration and the distribution of
      ectopically dying cells are specific characteristics of each mutant. Mutants are
      classified into four groups by these parameters. Class I: late focal neural
      degeneration mutants. These 18 mutants have restricted cell death mainly in the
      tectum and the dorsal hindbrain after 36 hours. The degeneration does not spread
      and disappears at later stages of development. Class II: early focal neural
      degeneration mutants. Ten mutants in this class exhibit transient restricted
      degeneration affecting mainly the diencephalon, the hindbrain and the spinal cord
      at 20 hours. The midbrain is less affected. The degeneration shifts to the dorsal
      diencephalon and the tectum at 36 hours. Class III: late spreading neural
      degeneration mutants. The 8 mutants in this class display a degeneration that is
      first seen in the tectum and subsequently spreads throughout the nervous system
      from 36 hours on. Class IV: early general neural degeneration mutants. This class
      of four mutants already shows overall cell degeneration in the nervous system at
      the 15-somite stage. Three of the class I mutants show a change in the pattern of
      gene expression in the anlage of a brain structure prior to the onset of
      degeneration. These results suggest that focal cell death may be a useful clue
      for the detection of early patterning defects of the vertebrate nervous system in
      regions devoid of visible landmarks.

PMID- 9007244
TI  - Mutations affecting development of the zebrafish inner ear and lateral line.
AB  - Mutations giving rise to anatomical defects in the inner ear have been isolated
      in a large scale screen for mutations causing visible abnormalities in the
      zebrafish embryo (Haffter, P., Granato, M., Brand, M. et al. (1996) Development
      123, 1-36). 58 mutants have been classified as having a primary ear phenotype;
      these fall into several phenotypic classes, affecting presence or size of the
      otoliths, size and shape of the otic vesicle and formation of the semicircular
      canals, and define at least 20 complementation groups. Mutations in seven genes
      cause loss of one or both otoliths, but do not appear to affect development of
      other structures within the ear. Mutations in seven genes affect morphology and
      patterning of the inner ear epithelium, including formation of the semicircular
      canals and, in some, development of sensory patches (maculae and cristae). Within
      this class, dog-eared mutants show abnormal development of semicircular canals
      and lack cristae within the ear, while in van gogh, semicircular canals fail to
      form altogether, resulting in a tiny otic vesicle containing a single sensory
      patch. Both these mutants show defects in the expression of homeobox genes within
      the otic vesicle. In a further class of mutants, ear size is affected while
      patterning appears to be relatively normal; mutations in three genes cause
      expansion of the otic vesicle, while in little ears and microtic, the ear is
      abnormally small, but still contains all five sensory patches, as in the wild
      type. Many of the ear and otolith mutants show an expected behavioural phenotype:
      embryos fail to balance correctly, and may swim on their sides, upside down, or
      in circles. Several mutants with similar balance defects have also been isolated
      that have no obvious structural ear defect, but that may include mutants with
      vestibular dysfunction of the inner ear (Granato, M., van Eeden, F. J. M.,
      Schach, U. et al. (1996) Development, 123, 399-413,). Mutations in 19 genes
      causing primary defects in other structures also show an ear defect. In
      particular, ear phenotypes are often found in conjunction with defects of neural
      crest derivatives (pigment cells and/or cartilaginous elements of the jaw). At
      least one mutant, dog-eared, shows defects in both the ear and another placodally
      derived sensory system, the lateral line, while hypersensitive mutants have
      additional trunk lateral line organs.

PMID- 9007245
TI  - Genetic analysis of fin formation in the zebrafish, Danio rerio.
AB  - In the zebrafish, Danio rerio, a caudal and pectoral fin fold develop during
      embryogenesis. At larval stages the caudal fin fold is replaced by four different
      fins, the unpaired anal, dorsal and tail fins. In addition the paired pelvic fins
      are formed. We have identified a total of 118 mutations affecting larval fin
      formation. Mutations in 11 genes lead to abnormal morphology or degeneration of
      both caudal and pectoral fin folds. Most mutants survive to adulthood and form a
      surprisingly normal complement of adult fins. Mutations in nine genes result in
      an increased or reduced size of the pectoral fins. Interestingly, in mutants of
      one of these genes, dackel (dak), pectoral fin buds form initially, but later the
      fin epithelium fails to expand. Expression of sonic hedgehog mRNA in the
      posterior mesenchyme of the pectoral fin bud is initiated in dak embryos, but not
      maintained. Mutations in five other genes affect adult fin but not larval fin
      development. Two mutants, longfin (lof) and another longfin (alf) have generally
      longer fins. Stein und bein (sub) has reduced dorsal and pelvic fins, whereas
      finless (fls) and wanda (wan) mutants affect all adult fins. Finally, mutations
      in four genes causing defects in embryonic skin formation will be briefly
      reported.

PMID- 9007246
TI  - Mutations affecting development of the zebrafish retina.
AB  - In a large scale screen for genetic defects in zebrafish embryogenesis we
      identified 49 mutations affecting development of the retina. Based on analysis of
      living embryos as well as histological sections, we grouped the isolated
      mutations into six phenotypic categories. (1) Mutations in three loci result in a
      loss of wild-type laminar pattern of the neural retina. (2) Defects in four loci
      lead to an abnormal specification of the eye anlagen. Only one eye frequently
      forms in this class of mutants. (3) Seven loci predominantly affect development
      of the outer retinal layers. Mutants in this category display cell loss mainly in
      the photoreceptor cell layer. (4) Nine mutations cause retardation of eye growth
      without any other obvious abnormalities in the retina. (5) A group of twelve
      mutations is characterized by nonspecific retinal degeneration. (6) Four
      mutations display retinal degeneration associated with a pigmentation defect.
      Finally, two mutations, one with absence of the ventral retina and one with an
      eye-specific pigmentation defect, are not classified in any of the above groups.
      The identified mutations affect numerous aspects of eye development, including:
      specification of the eye anlage, growth rate of the optic cup, establishment of
      retinal stratification, specification or differentiation of retinal neurons and
      formation of the dorsoventral axis in the developing eye.

PMID- 9007247
TI  - Mutations affecting development of the zebrafish ear.
AB  - In a large scale screen for genetic defects in zebrafish embryogenesis we
      identified mutations affecting several aspects of ear development, including:
      specification of the otic placode, growth of the otic vesicle (otocyst), otolith
      formation, morphogenesis of the semicircular canals and differentiation of the
      otic capsule. Here we report initial phenotypic and genetic characterization of
      20 of these mutations defining 13 independent loci. Embryos mutant at the quadro
      locus display abnormal specification of the otic placode. As revealed by dlx-3
      expression, the otic field in the mutant embryos is smaller or split into two
      fields. At later stages of development the ear of quadro mutants is frequently
      divided into two smaller, incomplete units. Four loci affect ear shape shortly
      after formation of the otic vesicle. All of them also display abnormal brain
      morphology. Mutations in five loci result in the absence of otolith formation;
      two of these also produce changes of ear morphology. Two loci, little richard and
      golas, affect morphology of the otic vesicle shortly before formation of the
      semicircular canals. In both cases the morphogenesis of the semicircular canals
      is disrupted. Finally, the antytalent locus is involved in late expansion of the
      ear structure. Analysis of mutations presented here will strengthen our
      understanding of vertebrate ear morphogenesis and provide novel entry points to
      its genetic analysis.

PMID- 9007248
TI  - Mutations affecting the formation and function of the cardiovascular system in
      the zebrafish embryo.
AB  - As part of a large-scale mutagenesis screen of the zebrafish genome, we have
      identified 58 mutations that affect the formation and function of the
      cardiovascular system. The cardiovascular system is particularly amenable for
      screening in the transparent zebrafish embryo because the heart and blood vessels
      are prominent and their function easily examined. We have classified the
      mutations affecting the heart into those that affect primarily either
      morphogenesis or function. Nine mutations clearly disrupt the formation of the
      heart. cloche deletes the endocardium. In cloche mutants, the myocardial layer
      forms in the absence of the endocardium but is dysmorphic and exhibits a weak
      contractility. Two loci, miles apart and bonnie and clyde, play a critical role
      in the fusion of the bilateral tubular primordia. Three mutations lead to an
      abnormally large heart and one to the formation of a diminutive, dysmorphic
      heart. We have found no mutation that deletes the myocardial cells altogether,
      but one, pandora, appears to eliminate the ventricle selectively. Seven mutations
      interfere with vascular integrity, as indicated by hemorrhage at particular
      sites. In terms of cardiac function, one large group exhibits a weak beat. In
      this group, five loci affect both chambers and seven a specific chamber (the
      atrium or ventricle). For example, the weak atrium mutation exhibits an atrium
      that becomes silent but has a normally beating ventricle. Seven mutations affect
      the rhythm of the heart causing, for example, a slow rate, a fibrillating pattern
      or an apparent block to conduction. In several other mutants, regurgitation of
      blood flow from ventricle to atrium is the most prominent abnormality, due either
      to the absence of valves or to poor coordination between the chambers with regard
      to the timing of contraction. The mutations identified in this screen point to
      discrete and critical steps in the formation and function of the heart and
      vasculature.

PMID- 9007249
TI  - Mutations affecting the cardiovascular system and other internal organs in
      zebrafish.
AB  - In a screen for early developmental mutants of the zebrafish, we have identified
      mutations specifically affecting the internal organs. We identified 53 mutations
      affecting the cardiovascular system. Nine of them affect specific landmarks of
      heart morphogenesis. Mutations in four genes cause a failure in the fusion of the
      bilateral heart primordia, resulting in cardia bifida. In lonely atrium, no heart
      venticle is visible and the atrium is directly fused to the outflow tract. In the
      overlooped mutant, the relative position of the two heart chambers is distorted.
      The heart is enormously enlarged in the santa mutant. In two mutants, scotch tape
      and superglue, the cardiac jelly between the two layers of the heart is
      significantly reduced. We also identified a number of mutations affecting the
      function of the heart. The mutations affecting heart function can be subdivided
      into two groups, one affecting heart contraction and another affecting the rhythm
      of the heart beat. Among the contractility group of mutants are 5 with no heart
      beat at all and 15 with a reduced heart beat of one or both chambers. 6 mutations
      are in the rhythmicity group and specifically affect the beating pattern of the
      heart. Mutations in two genes, bypass and kurzschluss, cause specific defects in
      the circulatory system. In addition to the heart mutants, we identified 23
      mutations affecting the integrity of the liver, the intestine or the kidney. In
      this report, we demonstrate that it is feasible to screen for genes specific for
      the patterning or function of certain internal organs in the zebrafish. The
      mutations presented here could serve as an entry point to the establishment of a
      genetic hierarchy underlying organogenesis.

PMID- 9007250
TI  - Hematopoietic mutations in the zebrafish.
AB  - We have identified mutations that perturb the formation or differentiation of the
      first embryonic blood cells in the zebrafish embryo. These 'primitive' red blood
      cells originate in the intermediate cell mass of the trunk, a derivative of the
      dorsal lateral plate mesoderm. By transfusion of blood between embryos we
      demonstrate that this cohort of cells provides the embryo with all, or nearly
      all, of its blood cells until at least day 5 postfertilization. Larval lethal
      mutations generated by ENU mutagenesis affect different steps in the development
      of these cells. Some cause defects in precursor generation, others defects in
      differentiation, and others an increase in cellular photosensitivity.

PMID- 9007251
TI  - Characterization of zebrafish mutants with defects in embryonic hematopoiesis.
AB  - As part of a large scale chemical mutagenesis screen of the zebrafish (Danio
      rerio) genome, we have identified 33 mutants with defects in hematopoiesis.
      Complementation analysis placed 32 of these mutants into 17 complementation
      groups. The allelism of the remaining 1 blood mutant is currently unresolved. We
      have categorized these blood mutants into four phenotypic classes based on
      analyses of whole embryos and isolated blood cells, as well as by in situ
      hybridization using the hematopoietic transcription factors GATA-1 and GATA-2.
      Embryos mutant for the gene moonshine have few if any proerythroblasts visible on
      the day circulation begins and normal erythroid cell differentiation is blocked
      as determined by staining for hemoglobin and GATA-1 expression. Mutations in five
      genes, chablis, frascati, merlot, retsina, thunderbird and two possibly unique
      mutations cause a progressive decrease in the number of blood cells during the
      first 5 days of development. Mutations in another seven genes, chardonnay,
      chianti, grenache, sauternes, weiflherbst and zinfandel, and two additional
      mutations result in hypochromic blood cells which also decrease in number as
      development proceeds. Several of these mutants have immature cells in the
      circulation, indicating a block in normal erythroid development. The mutation in
      zinfandel is dominant, and 2-day old heterozygous carriers fail to express
      detectable levels of hemoglobin and have decreasing numbers of circulating cells
      during the first 5 days of development. Mutations in two genes, freixenet and
      yquem, result in the animals that are photosensitive with autofluorescent blood,
      similar to that found in the human congenital porphyrias. The collection of
      mutants presented here represent several steps required for normal
      erythropoiesis. The analysis of these mutants provides a powerful approach
      towards defining the molecular mechanisms involved in vertebrate hematopoietic
      development.

PMID- 9007252
TI  - Mutations affecting development of zebrafish digestive organs.
AB  - The zebrafish gastrointestinal system matures in a manner akin to higher
      vertebrates. We describe nine mutations that perturb development of these organs.
      Normally, by the fourth day postfertilization the digestive organs are formed,
      the epithelial cells of the intestine are polarized and express digestive
      enzymes, the hepatocytes secrete bile, and the pancreatic islets and acini
      generate immunoreactive insulin and carboxypeptidase A, respectively. Seven
      mutations cause arrest of intestinal epithelial development after formation of
      the tube but before cell polarization is completed. These perturb different
      regions of the intestine. Six preferentially affect foregut, and one the hindgut.
      In one of the foregut mutations the esophagus does not form. Two mutations cause
      hepatic degeneration. The pancreas is affected in four mutants, all of which also
      perturb anterior intestine. The pancreatic exocrine cells are selectively
      affected in these four mutations. Exocrine precursor cells appear, as identified
      by GATA-5 expression, but do not differentiate and acini do not form. The
      pancreatic islets are spared, and endocrine cells mature and synthesize insulin.
      These gastrointestinal mutations may be informative with regard to patterning and
      crucial lineage decisions during organogenesis, and may be relevant to diabetes,
      congenital dysmorphogenesis and disorders of cell proliferation.

PMID- 9007253
TI  - Jaw and branchial arch mutants in zebrafish I: branchial arches.
AB  - Jaws and branchial arches together are a basic, segmented feature of the
      vertebrate head. Seven arches develop in the zebrafish embryo (Danio rerio),
      derived largely from neural crest cells that form the cartilaginous skeleton. In
      this and the following paper we describe the phenotypes of 109 arch mutants,
      focusing here on three classes that affect the posterior pharyngeal arches,
      including the hyoid and five gill-bearing arches. In lockjaw, the hyoid arch is
      strongly reduced and subsets of branchial arches do not develop. Mutants of a
      large second class, designated the flathead group, lack several adjacent
      branchial arches and their associated cartilages. Five alleles at the flathead
      locus all lead to larvae that lack arches 4-6. Among 34 other flathead group
      members complementation tests are incomplete, but at least six unique phenotypes
      can be distinguished. These all delete continuous stretches of adjacent branchial
      arches and unpaired cartilages in the ventral midline. Many show cell death in
      the midbrain, from which some neural crest precursors of the arches originate.
      lockjaw and a few mutants in the flathead group, including pistachio, affect both
      jaw cartilage and pigmentation, reflecting essential functions of these genes in
      at least two neural crest lineages. Mutants of a third class, including boxer,
      dackel and pincher, affect pectoral fins and axonal trajectories in the brain, as
      well as the arches. Their skeletal phenotypes suggest that they disrupt cartilage
      morphogenesis in all arches. Our results suggest that there are sets of genes
      that: (1) specify neural crest cells in groups of adjacent head segments, and (2)
      function in common genetic pathways in a variety of tissues including the brain,
      pectoral fins and pigment cells as well as pharyngeal arches.

PMID- 9007254
TI  - Jaw and branchial arch mutants in zebrafish II: anterior arches and cartilage
      differentiation.
AB  - In a large scale screen for mutants that affect the early development of the
      zebrafish, 109 mutants were found that cause defects in the formation of the jaw
      and the more posterior pharyngeal arches. Here we present the phenotypic
      description and results of the complementation analysis of mutants belonging to
      two major classes: (1) mutants with defects in the mandibular and hyoid arches
      and (2) mutants with defects in cartilage differentiation and growth in all
      arches. Mutations in four of the genes identified during the screen show specific
      defects in the first two arches and leave the more posterior pharyngeal arches
      largely unaffected (schmerle, sucker, hoover and sturgeon). In these mutants
      ventral components of the mandibular and hyoid arches are reduced (Meckel's
      cartilage and ceratohyal cartilage) whereas dorsal structures (palatoquadrate and
      hyosymplectic cartilages) are of normal size or enlarged. Thus, mutations in
      single genes cause defects in the formation of first and second arch structures
      but also differentially affect development of the dorsal and ventral structures
      within one arch. In 27 mutants that define at least 8 genes, the differentiation
      of cartilage and growth is affected. In hammerhead mutants particularly the
      mesodermally derived cartilages are reduced, whereas jellyfish mutant larvae are
      characterized by a severe reduction of all cartilaginous elements, leaving only
      two pieces in the position of the ceratohyal cartilages. In all other mutant
      larvae all skeletal elements are present, but consist of smaller and disorganized
      chondrocytes. These mutants also exhibit shortened heads and reduced pectoral
      fins. In homozygous knorrig embryos, tumor-like outgrowths of chondrocytes occur
      along the edges of all cartilaginous elements. The mutants presented here may be
      valuable tools for elucidating the genetic mechanisms that underlie the
      development of the mandibular and the hyoid arches, as well as the process of
      cartilage differentiation.

PMID- 9007255
TI  - Mutations affecting craniofacial development in zebrafish.
AB  - In a large-scale screen for mutations affecting embryogenesis in zebrafish, we
      identified 48 mutations in 34 genetic loci specifically affecting craniofacial
      development. Mutants were analyzed for abnormalities in the cartilaginous head
      skeleton. Further, the expression of marker genes was studied to investigate
      potential abnormalities in mutant rhombencephalon, neural crest, and pharyngeal
      endoderm. The results suggest that the identified mutations affect three distinct
      aspects of craniofacial development. In one group, mutations affect the overall
      pattern of the craniofacial skeleton, suggesting that the genes are involved in
      the specification of these elements. Another large group of mutations affects
      differentiation and morphogenesis of cartilage, and may provide insight into the
      genetic control of chondrogenesis. The last group of mutations leads to the
      abnormal arrangement of skeletal elements and may uncover important tissue-tissue
      interactions underlying jaw development.

PMID- 9007256
TI  - Zebrafish pigmentation mutations and the processes of neural crest development.
AB  - Neural crest development involves cell-fate specification, proliferation,
      patterned cell migration, survival and differentiation. Zebrafish neural crest
      derivatives include three distinct chromatophores, which are well-suited to
      genetic analysis of their development. As part of a large-scale mutagenesis
      screen for embryonic/early larval mutations, we have isolated 285 mutations
      affecting all aspects of zebrafish larval pigmentation. By complementation
      analysis, we define 94 genes. We show here that comparison of their phenotypes
      permits classification of these mutations according to the types of defects they
      cause, and these suggest which process of neural crest development is probably
      affected. Mutations in eight genes affect the number of chromatophores: these
      include strong candidates for genes necessary for the processes of pigment cell
      specification and proliferation. Mutations in five genes remove part of the wild
      type pigment pattern, and suggest a role in larval pigment pattern formation.
      Mutations in five genes show ectopic chromatophores in distinct sites, and may
      have implications for chromatophore patterning and proliferation. 76 genes affect
      pigment or morphology of one or more chromatophore types: these mutations include
      strong candidates for genes important in various aspects of chromatophore
      differentiation and survival. In combination with the embryological advantages of
      zebrafish, these mutations should permit cellular and molecular dissection of
      many aspects of neural crest development.

PMID- 9007257
TI  - Mutations affecting xanthophore pigmentation in the zebrafish, Danio rerio.
AB  - In a large-scale screen for mutants with defects in embryonic development we
      identified 17 genes (65 mutants) specifically required for the development of
      xanthophores. We provide evidence that these genes are required for three
      different aspects of xanthophore development. (1) Pigment cell formation and
      migration (pfeffer and salz); (2) pigment synthesis (edison, yobo, yocca and
      brie) and (3) pigment translocation (esrom, tilsit and tofu). The number of
      xanthophore cells that appear in the body is reduced in embryos with mutations in
      the two genes, salz and pfeffer. In heterozygous and homozygous salz and pfeffer
      adults, the melanophore stripes are interrupted, indicating that xanthophore
      cells have an important function in adult melanophore pattern formation. Most
      other genes affect only larval pigmentation. In embryos mutant for edison, yobo,
      yocca and brie, differences in pteridine synthesis can be observed under UV light
      and by thin-layer chromatography. Homozygous mutant females of yobo show a
      recessive maternal effect. Embryonic development is slowed down and embryos
      display head and tail truncations. Xanthophores in larvae mutant in the three
      genes esrom, tilsit and tofu appear less spread out. In addition, these mutants
      display a defect in retinotectal axon pathfinding. These mutations may affect
      xanthophore pigment distribution within the cells or xanthophore cell shape.
      Mutations in seven genes affecting xanthophore pigmentation remain unclassified.

PMID- 9007258
TI  - Genes controlling and mediating locomotion behavior of the zebrafish embryo and
      larva.
AB  - Zebrafish embryos and larvae have stage-specific patterns of motility or
      locomotion. Two embryonic structures accomplish this behavior: the central
      nervous system (CNS) and skeletal muscles. To identify genes that are
      functionally involved in mediating and controlling different patterns of
      embryonic and larval motility, we included a simple touch response test in our
      zebrafish large-scale genetic screen. In total we identified 166 mutants with
      specific defects in embryonic motility. These mutants fall into 14 phenotypically
      distinct groups comprising at least 48 genes. Here we describe the various
      phenotypic groups including mutants with no or reduced motility, mechanosensory
      defective mutants, 'spastic' mutants, circling mutants and motor circuit
      defective mutants. In 63 mutants, defining 18 genes, striation of somitic muscles
      is reduced. Phenotypic analysis provides evidence that these 18 genes have
      distinct and consecutive functions during somitic muscle development. The genes
      sloth (slo) and frozen (fro) already act during myoblast differentiation, while
      13 genes appear to function later, in the formation of myofibers and the
      organization of sarcomeres. Mutations in four other genes result in muscle
      specific degeneration. 103 mutations, defining at least 30 genes, cause no
      obvious defects in muscle formation and may instead affect neuronal development.
      Analysis of the behavioral defects suggests that these genes participate in the
      diverse locomotion patterns observed, such as touch response, rhythmic tail
      movements, equilibrium control, or that they simply confer general motility to
      the animal. In some of these mutants specific defects in the developing nervous
      system are detected. Mutations in two genes, nevermind (nev) and macho (mao),
      affect axonal projection in the optic tectum, whereas axon formation and
      elongation of motorneurons are disrupted by mutations in the diwanka (diw) and
      the unplugged (unp) genes.

PMID- 9007259
TI  - Genetic dissection of the retinotectal projection.
AB  - A systematic search for mutations affecting the retinotectal projection in
      zebrafish larvae was performed, as part of the large-scale Tubingen screen for
      homozygous diploid mutants in embryonic development. 2,746 inbred lines (F2
      families) from males mutagenized with ethylnitroso urea were screened. In wild
      type larvae, developing retinal axons travel along a stereotyped route to the
      contralateral optic tectum. Here, their terminals form a highly ordered
      retinotopic map. To detect deviations from this pattern, an axon tracing assay
      was developed that permits screening of large numbers of mutagenized fish. Two
      fluorescent tracer dyes (DiI and DiO) were injected at opposite poles of the eyes
      of day-5 aldehyde-fixed larvae. 12 hours later, retinal axons were labelled over
      their entire length, and could be observed through the intact skin. The assay
      procedure (aldehyde fixation, mounting, injection of dyes, microscopic analysis)
      took about 1 minute per fish. In total, 125,000 individual fish larvae were
      processed. During the screen, 114 mutations in approx. 35 genes were discovered.
      For the mutants subjected to complementation testing, the number of alleles per
      locus ranges from 1 to 15. The mutations affect distinct steps in the
      retinotectal pathway, from pathfinding between eye and tectum to map formation
      along the dorsal-ventral and the anterior-posterior axis of the tectum. Mutations
      that disturb axon pathfinding to the tectum for the most part do not disrupt
      retinotopic mapping, and vice versa. The majority of the mutants display
      associated defects in other tissues and die before day 10. These mutants provide
      new tools for studying the formation of neuronal maps. The results of this screen
      show that a large-scale genetic approach can be applied to relatively late and
      circumscribed developmental processes in the vertebrate brain.

PMID- 9007260
TI  - Zebrafish mutations affecting retinotectal axon pathfinding.
AB  - We have isolated mutants in the zebrafish Danio rerio that have defects in axonal
      connectivity between the retina and tectum. 5-day-old fish larvae were screened
      by labeling retinal ganglion cells with DiI and DiO and observing their axonal
      projections to and on the tectum. 82 mutations, representing 13 complementation
      groups and 6 single allele loci, were found that have defects in retinal ganglion
      cell axon pathfinding to the tectum. These pathfinding genes fall into five
      classes, based on the location of pathfinding errors between eye and tectum. In
      Class I mutant larvae (belladonna, detour, you-too, iguana, umleitung, blowout)
      axons grow directly to the ipsilateral tectal lobe after leaving the eye. Class
      II mutant larvae (chameleon, bashful) have ipsilaterally projecting axons and, in
      addition, pathfinding mistakes are seen within the eye. In Class III mutant
      larvae (esrom, tilsit, tofu) fewer axons than normal cross the midline, but some
      axons do reach the contralateral tectal lobe. Class IV mutant larvae (boxer,
      dackel, pinscher) have defects in axon sorting after the midline and retinal
      axons occasionally make further pathfinding errors upon reaching the
      contralateral tectal lobe. Finally, Class V mutant larvae (bashful, grumpy,
      sleepy, cyclops, astray) have anterior-posterior axon trajectory defects at or
      after the midline. The analysis of these mutants supports several conclusions
      about the mechanisms of retinal axon pathfinding from eye to tectum. A series of
      sequential cues seems to guide retinal axons to the contralateral tectal lobe.
      Pre-existing axon tracts seem not to be necessary to guide axons across the
      midline. The midline itself seems to play a central role in guiding retinal
      axons. Axons in nearby regions of the brain seem to use different cues to cross
      the ventral midline. Mutant effects are not all-or-none, as misrouted axons may
      reach their target, and if they do, they project normally on the tectum. The
      retinotectal pathfinding mutants reveal important choice points encountered by
      neuronal growth cones as they navigate between eye and tectum.

PMID- 9007261
TI  - Mutations disrupting the ordering and topographic mapping of axons in the
      retinotectal projection of the zebrafish, Danio rerio.
AB  - Retinal ganglion cells connect to their target organ, the rectum, in a highly
      ordered fashion. We performed a large-scale screen for mutations affecting the
      retinotectal projection of the zebrafish, which resulted in the identification of
      114 mutations. 44 of these mutations disturb either the order of RGC axons in the
      optic nerve and tract, the establishment of a topographic map on the tectum, or
      the formation of proper termination fields. Mutations in three genes, boxer,
      dackel and pinscher, disrupt the sorting of axons in the optic tract but do not
      affect mapping on the tectum. In these mutants, axons from the dorsal retina grow
      along both the ventral and the dorsal branch of the optic tract. Mutations in two
      genes, nevermind and who-cares, affect the dorsoventral patterning of the
      projection. In embryos homozygous for either of these mutations, axons from
      dorsal retinal ganglion cells terminate ventrally and dorsally in the tectum. In
      nevermind, the retinotopic order of axons along the optic nerve and tract is
      changed in a characteristic way as well, while it appears to be unaffected in who
      cares. Two mutations in two complementation groups, gnarled and macho, affect the
      anteroposterior patterning of the projection. In these mutants, nasodorsal axons
      branch and terminate too soon in the anterior tectum. In 27 mutants belonging to
      six complementation groups, retinal axons do not form normal termination fields.
      Some implications for models concerning the formation of topographic projections
      are discussed.

PMID- 9007263
TI  - A flipbook of zebrafish embryogenesis.

PMID- 9007262
TI  - A reference cross DNA panel for zebrafish (Danio rerio) anchored with simple
      sequence length polymorphisms.
AB  - The ultimate informativeness of the zebrafish mutations described in this issue
      will rest in part on the ability to clone these genes. However, the genetic
      infrastructure required for the positional cloning in zebrafish is still in its
      infancy. Here we report a reference cross panel of DNA, consisting of 520 F2
      progeny (1040 meioses) that has been anchored to a zebrafish genetic linkage map
      by 102 simple sequence length polymorphisms. This reference cross DNA provides:
      (1) a panel of DNA from the cross that was used to construct the genetic linkage
      map, upon which polymorphic gene(s) and genetic markers can be mapped; (2) a fine
      order mapping tool, with a maximum resolution of 0.1 cM; and (3) a foundation for
      the development of a physical map (an ordered array of clones each containing a
      known portion of the genome). This reference cross DNA will serve as a resource
      enabling investigators to relate genes or genetic markers directly to a single
      genetic linkage map and avoid the problem of integrating different maps with
      different genetic markers, as must be currently done when using randomly
      amplified polymorphic DNA markers, or as has occurred with human genetic linkage
      maps.

PMID- 9007264
TI  - Raymond U. Lemieux.

PMID- 9007265
TI  - Synthesis of glycyrrhizin analogues containing fluorinated beta(1-->2)-linked
      disaccharides.
AB  - For studies on the recognition mechanisms for Glycyrrhizin-induced biological
      activities, seven Glycyrrhizin analogues with 3'-, 4'-, 6'-, 3-, and 4
      fluorinated 2-O-beta-D-glucopyranosyl-beta-D-glucopyranoses (1-5) and 3- and 4
      fluorinated 2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranoses (6 and 7) were
      synthesized through a stepwise glycosylation procedure. 1,2-Di-O-acetyl-4,6-di-O
      benzyl-3-deoxy-3-fluoro- (13) and 1,2-di-O-acetyl-3,6-di-O-benzyl-4-deoxy-4
      fluoro-D-glucopyranose (14) were employed for the first beta-glycosylation of
      methyl glycyrrhetate, promoted with trimethylsilyl trifluoromethanesulfonate.

PMID- 9007266
TI  - PapG adhesin from E. coli J96 recognizes the same saccharide epitope when present
      on whole bacteria and as isolated protein.
AB  - Purified PapG adhesin from the genetically well-defined uropathogenic Escherichia
      coli strain J96, as well as whole bacteria, were bound to microtiter plates that
      carried covalently bound globotetraose and galabiose. The binding was inhibited
      by soluble saccharide derivatives corresponding to the glycolipids, including all
      di-, tri-, tetra-, and pentasaccharide fragments of the Forssman antigen and all
      monodeoxy analogues of galabiose. Analysis of the inhibition pattern showed no
      significant difference between purified adhesin and whole bacteria. The glucose
      unit at the reducing end of the natural saccharides was detrimental to PapG
      binding since deletion of the glucose unit increased the inhibitory power 10-20
      fold. The five hydroxyl groups HO-6, -2', -3', -4', -6' of the galabiose unit
      were shown to be important for PapG binding, presumably via intermolecular
      hydrogen bonds.

PMID- 9007267
TI  - Synthesis of a pentasaccharide corresponding to the repeating unit of the
      exopolysaccharide from Cryptococcus neoformans serovar D.
AB  - The assembly of the pentasaccharide repeating unit of the exopolysaccharide from
      Cryptococcus neoformans serovar D (i.e. 1) is described. The glucuronic acid
      residue in 1 is introduced as a glucopyranoside and oxidized in a later stage of
      the synthesis. Thus, iodonium ion-assisted glycosylation of the partially
      protected methyl mannopyranoside 11 with ethylthio donor 14 gave, after selective
      deprotection, disaccharide 18. Elongation of the latter with D-glucopyranoside 35
      gave trisaccharide 36. Subsequent protective group manipulations yielded the
      acceptor 37. Condensation of disaccharide donor 31 with trisaccharide acceptor 37
      yielded pentasaccharide 38. Protective group manipulations of 38 afforded 42, the
      glucoside of which was oxidized to yield the corresponding glucuronide 44.
      Hydrogenolysis of 44 gave the target pentasaccharide 1.

PMID- 9007268
TI  - Synthesis and biological activities of three sulfated sialyl Le(x) ganglioside
      analogues for clarifying the real carbohydrate ligand structure of L-selectin.
AB  - Sulfated sialyl Le(x) ganglioside analogues at C-6 of D-galactose, N-acetyl-D
      glucosamine, and of both D-galactose and N-acetyl-D-glucosamine residues have
      been synthesized, in order to clarify the structure of the real carbohydrate
      ligand of L-selectin. Coupling of the suitably protected N-acetyl-D-glucosaminyl
      beta (1-->3)-lactose derivatives 13 and 16 with the sialyl alpha(2-->3)-D
      galactopyranosyl trichloroacetimidates 10 and 12 (glycosyl donors), via
      glycosylation of 2-(trimethylsilyl)ethyl 4,6-O-benzylidene-beta-D
      galactopyranoside (1) with the phenyl 2-thioglycoside derivative (2) of N
      acetylneuraminic acid (Neu5Ac) using N-iodosuccinimide/TfOH, O-benzoylation,
      removal of the benzylidene group affording 5, selective 6-O-levulinoylation, O
      benzoylation, removal of the 2-(trimethylsilyl)ethyl group, and imidate
      formation, or via O-acetylation of 5, removal of the 2-trimethylsilyl)ethyl
      group, then imidate formation, gave the pentasaccharides 18-20. The glycosylation
      of the pentasaccharide acceptors (21-23) derived from 18-20 by removal of the 4
      methoxybenzyl group, with phenyl 1-thioglycoside derivative 27 of L-fucose using
      dimethyl(methylthio)sulfonium triflate (DMTST) afforded the corresponding
      hexasaccharides 28-30, which were transformed in good yields, via reductive
      removal of their benzyl groups, O-acetylation, selective removal of the 2
      (trimethylsilyl)ethyl group, imidate formation, coupling with (2S,3R,4E)-2-azido
      O-benzoyl-4-octadecene-1,3-diol (35) in the presence of boron trifluoride
      etherate, selective reduction of the azido group, coupling with octadecanoic
      acid, selective removal of the levulinoyl groups, treatment with sulfur trioxide
      pyridine complex, then removal of the protecting groups, into the desired
      sulfated sialyl Le(x) ganglioside analogues 50-52.

PMID- 9007270
TI  - Deoxyiminoalditols from aldonolactones--V. Preparation of the four stereoisomers
      of 1,5-dideoxy-1,5-iminopentitols. Evaluation of these iminopentitols and three
      1,5-dideoxy-1,5-iminoheptitols as glycosidase inhibitors.
AB  - The four stereoisomeric 1,5-dideoxy-1,5-iminopentitols with D-arabino-(D-lyxo-)
      (3), ribo- (9), L-lyxo (L-arabino-) (13) and xylo-(18) configurations were
      synthesized. The corresponding aldonolactones (1, 7 and 11) or aldonic acid ester
      (15b) having a leaving group at C-5 gave by reaction with aqueous ammonia, the 5
      amino-5-deoxy-1,5-lactams, 2, 8, 12 and 17, respectively. Reduction of the lactam
      function using sodium borohydride/acetic or trifluoroacetic acid, or borane
      dimethyl sulfide complex yielded the iminopentitols. The compounds 3, 9, 13 and
      18, together with the three 1,5-dideoxy-1,5-iminoheptitols 19,20 and 21 were
      tested for inhibition of the glycosidase activities present in an extract from
      human liver. Compound 18 was a potent and 19 a moderately good inhibitor of beta
      glucosidase. Compound 3 together with 19, 20 and 21, all having D-arabino
      configuration at the hydroxy-substituted carbon atoms, were good inhibitors of
      alpha-L-fucosidase.

PMID- 9007271
TI  - Synthesis of oligosaccharides corresponding to structures found in capsular
      polysaccharides of Cryptococcus neoformans--II.
AB  - Formula 1 depicts a generalized structure of the capsular polysaccharides of four
      serotypes of the opportunistic microorganism Cryptococcus neoformans, which
      appears as one of the major infections in the late stages of development of AIDS.
      Syntheses are now described of two tetrasaccharides with corresponding
      structures. These are methyl O-alpha-D-mannopyranosyl-(1-->3)-[O-beta-D
      xylopyranosyl-(1-->2)] -O-alpha-D-mannopyranosyl-(1-->3)-alpha-D-mannopyranoside
      and methyl O-alpha-D-mannopyranosyl-(1-->3)-[O-beta-D-glucopyranosyluronic acid
      (1-->2)]-O-alpha-D-mannopyranosyl-(1-->3)-alpha-D-mannopyranoside.

PMID- 9007269
TI  - Design and chemoenzymatic synthesis of thiooligosaccharide inhibitors of 1,3:1,4
      beta-D-glucanases.
AB  - A successful chemoenzymatic synthesis of oligosaccharides with an interglucosidic
      sulfur atom as inhibitors of 1,3:1,4-D-glucanases is described. The key compound
      3a was synthesized from acetylated 1-thio-beta-laminaribiose 4 and the methyl 4'
      O-triflyl-lactoside 5. After de-O-acylation, the tetrasaccharide 3b was used as
      an acceptor and glucose-1-P as a donor in a phosphorolytic elongation catalysed
      by cellodextrin phosphorylase from Clostridium thermocellum. The expected
      pentasaccharide 2a and hexasaccharide 1 were isolated in 56% and 13% yield,
      respectively. As expected, the thiooligosaccharides 1, 2a, and 3b were resistant
      to enzymatic cleavage by 1,3:1,4-beta-D-glucanase isolated from Bacillus
      licheniformis. Furthermore, they have been shown to act as competitive inhibitors
      of the hydrolysis of the chromophoric trisaccharide substrate 11 by this enzyme.

PMID- 9007272
TI  - Synthesis of glycopeptides with phytoalexin elicitor activity--III. Syntheses of
      hexaglycosyl hexapeptides and a nonaglycosyl hexapeptide.
AB  - A block synthesis of the model compound for the phytoalexin elicitor-active
      glycoprotein is described. Combination of the C-terminus free compounds, N-(9
      fluorenylmethoxycarbonyl)-O-(tert-butyl)-L-seryl-L-proline (1) or N-(9
      fluorenylmethoxycarbonyl)-(2,3,4,6-tetra-O-acetyl-beta-D-g luc opyranosyl) -(1-
      >6)-(2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl)-(1-->6) -(2,3,4-tri-O-acetyl
      alpha-D-mannopyranosyl)-L-seryl-L-proline (2) with the N-terminus free compounds,
      2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl -(1-->6)-(2,3,4-tri-O-acetyl-alpha-D
      mannopyranosyl)-(1-->6)-(2,3,4-tri- O -acetyl-alpha-D-mannopyranosyl)-L-seryl-L
      prolyl-L-seryl-L-proline methyl ester (4), O-(tert-butyl)-L-seryl-L-prolyl
      (2,3,4,6-tetra-O-acetyl-beta-D -glucopyranosyl)-(1-->6)-(2,3,4-tri-O-acetyl-alpha
      D-mannopyranosyl) -(1-->6)-(2,3,4-tri-O-acetyl- alpha-D-mannopyranosyl)-L-seryl-L
      proline methyl ester (6) or 2,3,4,6-tetra-O-acetyl-beta-D- glucopyranosyl -(1-
      >6)-(2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl)-(1-->6) -(2,3,4-tri-O-acetyl
      alpha-D-mannopyranosyl)-L-seryl-L-prolyl -(2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranosyl)-(1-->6) -(2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl)-(1-->6) 
      (2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl)-L-seryl-L-proline methyl ester (8),
      by use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) gave three
      hexaglycosyl hexapeptides and a nonaglycosyl hexapeptide derivatives (9, 11, 14,
      and 17). These N-terminus free compounds were derived from triglycosyl
      tetrapeptides (3 and 5) or a hexaglycosyl tetrapeptide (7) on selective deblock
      reaction by morpholine. The hexaglycosyl hexapeptides (10, 13, and 16) and the
      nonaglycosyl hexapeptide (18) have been prepared by the convergent block
      synthesis.

PMID- 9007273
TI  - Glycopeptide mimics of mammalian Man9GlcNAc2. Ligand binding to mannan-binding
      proteins (MBPs).
AB  - A novel and simple approach for rational design of oligosaccharide mimics has
      been developed. Mammalian high-mannose triantennary structure Man9GlcNac2 has
      been subjected to molecular modelling using the NMR data available on structural
      fragments of the oligosaccharide. The analysis indicated four different low
      energy conformations, and the spatial arrangement of terminal disaccharides of
      the oligosaccharide antennae were stimulated with glycopeptides carrying
      disaccharides by applying weak constraints between the saccharide parts in MD
      simulations on a large array of tri- to octaglycopeptides. The five glycopeptides
      exhibiting the best fit with the four minimum energy confirmations of the
      oligosaccharide were synthesized by solid phase glycopeptide assembly using
      glycosylated fluoren-9-ylmethyloxycarbonyl-amino acid-O-pentafluorophenyl esters
      as building blocks. The glycan was acyl protected alpha-D-Man-(1-->2)-alpha-D-Man
      and Ser, Thr and Hyp were the glycosylated amino acids. The deprotected and
      purified glycopeptides were subjected to NMR analysis for characterization, and
      in order to investigate the cis-trans isomerism of the carbimide bonds to Hyp.
      The glycopeptides were tested for their ability to inhibit binding of mannan
      binding protein to mannan from Saccharomyces cerevisiae. They were found to be
      weak inhibitors showing no indication of multivalent interaction with the mannan
      binding protein.

PMID- 9007274
TI  - A new strategy for stereoselective synthesis of sialic acid-containing
      glycopeptide fragment.
AB  - Sialic acid donor 5, which has a thiophenyl group as a stereocontrolling
      auxiliary and thiomethyl group as a leaving group was prepared and subjected to
      model glycosylation. Reactions with acceptor substrates 6, 7, and 8 gave coupled
      products 9b, 10b, and 11b, respectively, in a higher efficiency than previously
      observed for the bromide 1a. This reaction was further applied to the synthesis
      of protected glyco-amino acid fragment 12, that is strategically designed for the
      synthesis of sialic acid containing glycopeptides.

PMID- 9007275
TI  - N-Tetrachlorophthaloyl (TCP) for ready protection/deprotection of amino sugar
      glycosides.
AB  - The tetrachlorophthaloyl (TCP) group can be utilized when imidic protection of an
      amine is desired and durability of the protecting group to conditions ranging
      from mildly basic to harshly acidic is required. Installation can be accomplished
      in two steps by treating the free base with the commercially available TCP
      anhydride, and then closing the imidic ring with acetic anhydride and pyridine.
      Cleavage is effected by 2-4 eq of ethylenediamine under very mild conditions
      under which esters and glycopeptides have been shown to be stable, and
      racemization of amino acid residues does not occur. Unsubstituted phthalimides,
      even within the same molecule, are also unaffected during TCP cleavage. TCP
      protecting groups serve as beta-directors on donors and can also be present on
      acceptor species during electrophilic couplings in oligosaccharide synthesis.

PMID- 9007276
TI  - Unexpected carbohydrate cross-binding by Escherichia coli heat-labile
      enterotoxin. Recognition of human and rabbit target cell glycoconjugates in
      comparison with cholera toxin.
AB  - The bacterial protein enterotoxins, cholera toxin (CT) of Vibrio cholerae and
      heat-labile toxin (LT) of Escherichia coli, induce diarrhea by enhancing the
      secretory activity of the small intestine of man and rabbit (animal model). This
      physiological effect is mediated by toxin binding to a glycolipid receptor, the
      ganglioside GM1, Gal beta 3GalNAc beta 4(NeuAc alpha 3)GAl beta 4Glc beta 1Cer.
      However, LT, but not CT, was recently shown by us to bind also to paragloboside,
      Gal beta 4GlcNAc beta 3Gal beta 4Glc beta 1Cer, identified in the target cells.
      By molecular modeling of this tetrasaccharide in the known binding site of LT,
      the saccharide-peptide interaction was shown to be limited to the terminal
      disaccharide (N-acetyllactosamine). This sequence is expressed in many
      glycoconjugates, and we have therefore assayed glycolipids and glycoproteins
      prepared from the target tissues. In addition to paragloboside, receptor activity
      for LT was detected in glycoproteins of human origin and in polyglycosylceramides
      of rabbit. However, CT bound only to GM1. Two variants of LT with slightly
      different sequences, human (hLT) and porcine (pLT), were identical in their
      binding to target glycoproteins and polyglycosylceramides, but different
      regarding paragloboside, which was positive for pLT but negative for hLT. This
      difference is discussed on basis of modeling, taking in view the difference at
      position 13, with Arg in pLT and His in hLT. Although N-acetyllactosamine is
      differently recognized in form of paragloboside by the two toxin variants, we
      speculate that this sequence in human glycoproteins and rabbit
      polyglycosylceramides is the basis for the common binding. Much work remains,
      however, to clear up up this unexpected sophistication in target recognition.

PMID- 9007277
TI  - Substituted glycals as probes of glycosidase mechanisms.
AB  - D-Glucal and a series of substituted derivatives have been tested as substrates,
      inhibitors and inactivators of the Agrobacterium faecalis beta-glucosidase in
      order to probe structure/function relationships in this enzyme. D-Glucal is shown
      to be a substrate (kcat = 2.3 min-1, Km = 0.85 mM) undergoing hydration with
      stereospecific protonation from the alpha-face to yield 2-deoxy-beta-D-glucose. 1
      Methyl-D-glucal surprisingly serves as only a poor substrate (kcat = 0.056 min-1,
      Km = 57 mM), also undergoing protonation from the alpha-face. 2-Fluoro-D-glucal,
      however is completely inert, as a result of inductive destabilisation of the
      oxocarbenium ion-like transition state for protonation, and functions only as a
      relatively weak (Ki = 24 mM) inhibitor. Similar behaviour was seen with almond
      beta-glucosidase and yeast alpha-glucosidase and for the interaction of 2-fluoro
      D-galactal with Escherichia coli beta-galactosidase. A series of of alpha, beta
      unsaturated glucal derivatives was also synthesised and tested as potential
      substrates, inhibitors or inactivators of A. faecalis beta-glucosidase. Of these
      only 1-nitro-D-glucal functioned as a time dependent, irreversible inactivator
      (ki = 0.011 min-1, Ki = 5.5 mM), presumably acting as a Michael acceptor.
      Electrospray mass spectrometric analysis revealed multiple labeling of the enzyme
      by this inactivator, lessening its usefulness as an affinity label. Less reactive
      Michael acceptor glycals which might have been more specific (1-cyano-, 2-cyano-,
      1-carboxylic acid, 1-carboxylic acid methyl ester) unfortunately did not function
      as inactivators or substrates, only as relatively weak reversible inhibitors (Ki
      = 3-96 mM).

PMID- 9007278
TI  - Novel aspects of interaction between UDP-gal and GlcNAc beta-1,4
      galactosyltransferase: transferability and remarkable inhibitory activity of UDP
      (mono-O-methylated gal), UDP-Fuc and UDP-man.
AB  - Four mono-O-methylated and one mono-O-acetylated UDP-D-Gal analogues and UDP-L
      Fuc were synthesized. 2-O-Methyl-D-galactose residue was enzymatically
      transferred to give 2'-O-methyllactosaminide in high yield. UDP-Fuc and UDP-Man
      showed potent inhibitory activities against beta-1,4-galactosyltransferase.
      Structural requirement and steric allowance for the ground and transition states
      of the enzyme reaction were discussed.

PMID- 9007279
TI  - Macromolecular recognition: effect of multivalency in the inhibition of binding
      of yeast mannan to concanavalin A and pea lectins by mannosylated dendrimers.
AB  - The synthesis and binding properties of a new family of high affinity alpha-D
      mannopyranoside ligands are described. The synthesis of the new multivalent
      ligands is based on the scaffolding of multiantennary branches of L-lysine
      residues having electrophilic N-chloroacetylated end groups as core structures.
      An alpha-D-mannopyranoside with p-substituted aryl aglycon ending with a thiol
      group was prepared and covalently attached to each of the branches of the
      dendritic structures. The resulting glycodendrimers with 2 (12), 4 (14), 8 (16),
      and 16 (18) mannoside residues were tested for their relative inhibitory potency
      by solid-phase enzyme-linked lectin assays (ELLA) using methyl and p-nitrophenyl
      alpha-D-mannopyranosides as standards. Concentrations necessary for 50%
      inhibition (IC50s) of binding of yeast mannan to Jack bean phytohemagglutinin
      (Canavalia ensiformis, concanavalin A) and to pea lectin (Pisum sativum) were
      determined. Analogous mannosylated copolyacrylamides were also prepared for
      comparison. The IC50 values were also plotted as a function of dendrimer
      valencies. The inhibitions showed 16-mer 18 to be approximately 600- and 2000
      fold more potent than methyl alpha-D-mannopyranoside, and 66- and 1383-fold more
      potent than p-nitrophenyl alpha-D-mannopyranosides with Con A and pea lectins,
      respectively. Even when these numbers are expressed relative to single
      mannopyranoside residues per dendrimers, the relative potencies against the
      aromatic mannoside are still 4- and 86-fold better against Con A and pea lectins.
      These results unequivocally indicate that the optimum inhibitory binding
      properties of the new mannosylated dendrimers vary with both dendrimers and
      lectin valencies.

PMID- 9007280
TI  - Analysis of the binding specificities of oligomannoside-binding proteins using
      methylated monosaccharides.
AB  - The binding specificities of the closely related lectins from Canavalia
      ensiformis and Dioclea grandiflora were examined using specifically O-alkylated
      mono- and disaccharides. Both lectins accept any substitution at the
      monosaccharide C2 hydroxyl group. The binding energy of C2-alkylated ligands
      concanavalin A complexes increases by 1 kcal mol-1 for the C2-O-ethyl ligand,
      while the binding energies of the corresponding complexes with the Dioclea lectin
      are identical. Both lectins accept methyl, but not ethyl, substitution of the C3
      hydroxyl, in contrast to earlier reports. The results are interpreted in terms of
      existing models of the concanavalin A binding site. While the results are
      consistent with a model of the concanavalin A extended binding site that places
      the non-reducing terminus of all disaccharides in the monosaccharide binding
      site, they point to the dangers of interpreting the binding behavior of unnatural
      saccharide ligands on the basis of crystallographic data obtained with native
      ligands.

PMID- 9007281
TI  - How do antibodies and lectins recognize histo-blood group antigens? A 3D-QSAR
      study by comparative molecular field analysis (CoMFA).
AB  - The cross-reaction patterns of nine antibodies and three lectins against 12 H
      type 2 related oligosaccharides have been analysed by means of 3D-QSAR study.
      Three-dimensional descriptors of the molecular properties have been used in
      comparative molecular field analysis (CoMFA). Three different alignments were
      considered for the oligosaccharides. One, based on the superimposition of the
      oligosaccharide core, could be correlated to most of the antibody activities. A
      second alignment, based on a superimposition of the fucose residue, had to be
      taken into account for explaining the binding properties of Ulex europaeus
      isolectin I. Analysis of the QSAR data gives indications on the carbohydrate
      epitopes essential for antibody recognition and yields some insights about the
      nature of the molecular recognition. This study complements previous biochemical
      estimates of the H type 2 related oligosaccharide binding areas (Mollicone, R.;
      Cailleau, A.; Imberty, A.; Gane, P.; Perez, S.; Oriol, R. Glycoconj. J. 1996, 13,
      263-271).

PMID- 9007282
TI  - Synthesis and conformational studies of the tyvelose capped, Lewis-x like
      tetrasaccharide epitope of Trichinella spiralis.
AB  - Chemical synthesis and high resolution NMR studies are reported for the
      tetrasaccharide epitope and constituent structures that occur as terminal
      elements of Trichinella spiralis cell surface glycans. The 2
      (trimethylsilyl)ethyl and methyl glycosides of Lewis-x type trisaccharides, in
      which beta GalNAc replaces beta Gal were synthesized from monosaccharide synthons
      utilizing thioglycoside and halide-ion glycosylation methods. The unique 3,6
      dideoxy-beta-D-arabinohexopyranosyl residue that caps the structure was
      introduced to selectively protected 2-(trimethylsilyl)ethyl and methyl
      trisaccharide glycosides by utilizing an insoluble silver zeolite catalyst and a
      glycosyl halide. In separate reactions not only were the principal targets
      obtained but also the corresponding alpha-linked tetrasaccharides. A comparison
      of the NMR spectra of the methyl tetrasaccharide glycosides showed that at the
      site of the alpha-linked tyvelose structure, specific GalNAc resonances (C-1, C
      2, C-3) possess uncharacteristically wide 13C (8-21 Hz) and 1H lines. The beta
      linked tetrasaccharide glycoside, that represents the native parasite epitope,
      exhibited only narrow line widths (3 Hz, 13C). Since NOE derived distance
      constraints for the alpha-linked tyvelose structure were not consistent with the
      existence of unusual glycosidic conformers, the origin of the limited number of
      wide lines was attributed to local rigidity in the GalNAc residue, at the site of
      tyvelose glycosylation.

PMID- 9007283
TI  - Preparations of antigens and immunoadsorbents corresponding to the Streptococcus
      group A cell-wall polysaccharide.
AB  - The allyl glycosides of a tri-, penta- and hexasaccharide corresponding to the
      Streptococcus Group A cell-wall polysaccharide were coupled to solid or soluble
      supports to give immunoaffinity columns and neoglycoproteins, respectively.
      Cysteamine hydrochloride was added to the allyl glycosides and the resulting
      cysteamine adducts were used for subsequent coupling to linkers via the amine
      functionality. The tri- and penta-saccharide cysteamine adducts were coupled
      directly to the azalactone-derivatized 3M Emphase Biosupport Medium AB 1 to yield
      two affinity columns. The penta- and hexa- saccharides were coupled to bovine
      serum albumin or ovalbumin via the conjugate addition of the epsilon-amino groups
      of lysines on the proteins with the N-acryloylated sugars or the oligosaccharide
      squarate adducts, derived in turn from the cysteamine adducts. The efficiency of
      the above methods is compared.

PMID- 9007284
TI  - New synthetic trisaccharide inhibitors for N-acetylglucosaminyltransferase-V.
AB  - The trisaccharide octyl 2-acetamido-2-deoxy-beta-D-glucopyranosyl -(1-->2)-alpha
      D-mannopyranosyl-(1-->6)-beta-D-glucopyranoside (5) is an acceptor substrate for
      N-acetylglucosaminyltransferase-V (EC 2.4.1.155) which adds a beta-GlcNAc residue
      to OH-6 of the central Man-residue. In the present work, 10 analogues of 5, each
      missing the potentially reactive OH-6 group, were chemically synthesized. The key
      intermediate used was octyl 2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1-->2)-6
      amino-6-deoxy-4-O -methyl-alpha-D-mannopyranosyl-(1-->6)-beta-D-glucopyranoside
      (6a), which was synthesized in stepwise fashion by sequential coupling of
      protected monosaccharide residues. The 6'-amino group in 6a, was then selectively
      derivatized by either acylation or alkylation with hydrophobic, hydrophilic,
      charged, aromatic and potential covalently inactivating groups. The 10
      trisaccharide analogues thus produced were evaluated for inhibition against
      GlcNAcT-V isolated from hamster kidney. All of the compounds were competitive
      inhibitors with Ki values ranging from 21 to 297 microM. These results indicate
      that acceptor substrate (or inhibitor)-enzyme complex does not involve critical
      recognition contacts at the position of transfer.

PMID- 9007285
TI  - Acceptor hydroxyl group mapping for human milk alpha 1-3 and alpha 1-3/4
      fucosyltransferases.
AB  - Two different fucosyltransferases (Fuc-Ts) have been isolated from human milk, an
      alpha 1-3 Fuc-T and an alpha 1-3/4 Fuc-T, for mapping of their acceptor binding
      sites. Kinetic studies employing a series of monodeoxygenated and modified Gal
      beta 1-->4Glc-NAc beta OR and Gal beta 1-->3GlcNAc beta OR acceptor substrates
      showed that modifications are tolerated at every hydroxyl group in these
      substrates except for 6-OH of galactose and 3- or 4-OH of N-acetylglucosamine.
      Deoxygenation at these positions rendered these compounds inactive as both
      substrates and inhibitors. These essential hydroxyl groups, which are required
      for recognition of the substrates, are identical to the key polar groups that
      have previously been reported for cloned FucTs III, IV and V.

PMID- 9007311
TI  - Familial Alzheimer's disease co-segregates with a Met146I1e substitution in
      presenilin-1.
AB  - The presenilin-1 (PS-1)/S 182 gene at chromosome 14q24.3 is, when mutated, the
      most common disease gene in autosomal dominant early-onset Alzheimer's disease.
      Substitution of methionine 146 of the gene product for either valine or leucine
      co-segregates with Alzheimer's disease with the age of onset in the late thirties
      or early forties. Here we describe a new substitution of methionine 146 for
      isoleucine that co-segregates with Alzheimer's disease with age of the onset in
      the early forties. All identified missense mutations in methionine codon 146
      replace one hydrophobic amino acid (Met) with another (Val, Leu, Ile) and
      correspond to any nucleotide change at the first or third position of the codon.
      Second position mutations invariably lead to replacement of the hydrophobic
      methionine with a hydrophilic amino acid that may severely affect the function of
      the protein. The fact that no second position mutations have been identified so
      far may support the hypothesis that the protein product of PS-1 plays a crucial
      role during development.

PMID- 9007312
TI  - Late juvenile metachromatic leukodystrophy (MLD) in three patients with a similar
      clinical course and identical mutation on one allele.
AB  - Metachromatic leukodystrophy (MLD) is an autosomal, recessively inherited,
      lysosomal storage disease caused by arylsulfatase A (ASA) activity deficit.
      Arylsulfatase A initiates the degradation of sulfatide (cerebroside sulfate),
      which is an essential component of myelin. The main clinical symptoms are caused
      by progressive demyelination. At least 34 MLD-related ASA mutations are known to
      date. I179S (E3P799) is a disease-related mutation, described for the first time
      by Fluharty in 1991. This aberration appears to substantially reduce, but not
      completely eliminate ASA activity, and was detected in individuals with late
      onset (juvenile or adult) forms of MLD. This paper deals with the peculiar
      clinical course in three unrelated juveniles with late-onset MLD carrying the
      I179S mutations on one allele. In the three described patients with the I179S
      mutation, psychiatric disturbances and intellectual impairment dominated the
      clinical picture, while the neurological lesions progressed more slowly. Although
      the symptoms appeared rather early, making it possible to classify this as the
      juvenile type of MLD, the clinical picture was more that of the adult type.
      Although the mutations on the second allele in our patients are unknown, one can
      speculate, that the mutation I179S plays an important role in the characteristic
      clinical course (psychiatric impairment, slower neurological deterioration, but
      relatively early onset). It seems that I179S mutation on one allele with another
      mutation on the other allele reduces ASA activity, but the enzyme can still cope
      with a part of the substrate influx, leading to late-juvenile-onset MLD with such
      strikingly similar phenotypes remaining a little bit of the adult (psychiatric)
      type. This could be one more argument in favour of phenotype-genotype correlation
      in patients with MLD.

PMID- 9007313
TI  - Apolipoprotein E e4 allele in the normal elderly: neuropsychologic and brain MRI
      correlates.
AB  - The presence of the apolipoprotein E e4 allele has been considered to be a risk
      factor for Alzheimer's disease and vascular dementia. We therefore used demanding
      neuropsychologic testing and brain MRI to determine if elderly normals with at
      least one e4 allele demonstrate subclinical changes in cognition and a higher
      frequency of brain atrophy or silent ischemic brain damage. The study population
      consisted of 214 randomly selected individuals aged 50 to 75 years without
      neuropsychiatric or general disease. There were 175 (81.8%) subjects without and
      39 (18.2%) with at least one e4 allele. The two groups were comparable for age,
      length of education, verbal intelligence, mood and major vascular risk factors.
      Apolipoprotein E e4 carriers performed significantly worse than non-carriers when
      assessed for learning and memory abilities, while there were no differences in
      test results of conceptualization, attention, speed of mental processing and
      visuopractical skills. There were no between-group differences for thromboembolic
      and lacunar infarcts, white matter hyperintensity grading and the
      semiautomatically measured white matter hyperintensity area. The extent of sulcal
      and ventricular widening as well as hippocampal and parahippocampal volumes were
      also similar between the comparative subsets. We conclude that the apolipoprotein
      E e4 allele is associated with subtle learning and memory deficits in normal
      elderly persons and may therefore be suggested a marker for accelerated cognitive
      aging. In this group of subjects it was not associated with brain parenchymal
      changes as demonstrated by MRI.

PMID- 9007314
TI  - Trisomy 13/trisomy 18 mosaicism in an infant.
AB  - Cytogenetic analysis of amniotic fluid cells from a 31-week-old fetus suffering
      from polyhydramnios revealed that there were two cell lines, each with either
      trisomy 13 or trisomy 18. We studied the origin and mechanism for formation of
      this unique mixoploidy by tracing chromosomal heteromorphisms as genetic markers,
      and showed no discordance of parent-child transmission between the two cell lines
      in any of the heteromorphisms examined. The result indicated that the mixoploidy
      is not chimerism but mosaicism and that the mechanism of mosaic development is
      most likely due to two non-disjunctional events which had occurred independently
      at the two-cell stage of the zygote. A girl was born at the 38th gestational week
      and her clinical features were mainly those for trisomy 13. Chromosome analysis
      of the newborn confirmed +13/+18 mosaicism in fibroblasts from the skin and
      chorionic plate, while cord blood lymphocytes and chorionic villus cells showed
      only the +18 cell line.

PMID- 9007315
TI  - Variable clinical expression in a family with OI type IV due to deletion of three
      base pairs in COL1A1.
AB  - We have studied a family with autosomal dominant osteogenesis imperfecta (OI)
      type IV. Electrophoresis of collagen produced by cultured fibroblasts revealed a
      slower migrating population of collagen I. Cyanogen bromide peptide mapping
      localised the structural defect to the area of the alpha 1(1)CB3 peptide.
      Subsequent sequencing revealed a deletion of nucleotides 1964-1966 in exon 27 of
      COL1A1. By means of restriction enzyme analysis, the deletion could be detected
      in all affected family members. This in-frame deletion resulted in the removal of
      alanine-438 and Glu437Asp substitution in the pro alpha 1(I) collagen chain.
      Clinical variation was considerable among affected family members. The most
      consistent clinical features were reduced height and extraosseous manifestations
      of OI.

PMID- 9007316
TI  - Asymptomatic and late-onset ornithine transcarbamylase (OTC) deficiency in males
      of a five-generation family, caused by an A208T mutation.
AB  - In a large five-generation Polish family, late-onset ornithine transcarbamylase
      (OTC) deficiency in males segregated with the missense mutation Ala208Thr
      (A208T), and all heterozygous females were asymptomatic. No other mutations were
      found in the coding sequences and intron-exon boundaries of the OTC gene.
      Surprisingly, the mutation originated from the great-grandfather of the index
      patient who died at age 59 of liver carcinoma. He never had dietary restrictions
      or hyperammonemic spells throughout life and appears to be the oldest male
      reported with OTC deficiency. The index patient had a severe OTC deficiency (3%
      of normal). Eight males died suddenly at ages 4 months to 23 years (average 14
      years) after a foudroyant episode triggered by a common infection. The patients
      remained undiagnosed for 28 years because a metabolic defect was not considered
      to be the cause of the acute episodes. Recognition of the familial pattern of
      inheritance was initially unnoticed since the patients were admitted to eight
      different hospitals. DNA analysis predicted that two 'healthy' boys also had OTC
      deficiency, which was confirmed by abnormal results of allopurinol challenge
      tests. Initial suspicion of OTC deficiency in such families is complicated, since
      symptoms can develop at any age, or even remain absent. This obscures the typical
      pattern of X-linked inheritance in small families.

PMID- 9007317
TI  - Dermatological manifestations of 71 Down syndrome children admitted to a clinical
      genetics unit.
AB  - Seventy-one children with Down syndrome who were admitted consecutively to
      Hacettepe University Children's Hospital Genetics department were examined for
      skin disorders. None of the patients suffered directly from skin disorders. All
      were living with their families and had approximately similar living conditions.
      There were 29 children with palmoplantar hyperkeratosis (40.8%), seven with
      xerosis (9.8%), 22 with seborrheic dermatitis (30.9%), 14 with fissured tongue
      (20%), eight with geographic tongue (11.2%), and nine with cutis marmorata
      (12.6%). Nine had normal skin findings. Since palmoplantar hyperkeratosis may be
      a result of vitamin A deficiency, the serum vitamin A levels of these patients
      were evaluated. There was no statistical difference between vitamin A levels of
      the children with Down syndrome and the control group.

PMID- 9007318
TI  - Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p in fetuses with
      holoprosencephaly.
AB  - Chromosome aberrations, mendelian mutations and exogenous agents can cause
      holoprosencephaly. Therefore, etiologic evaluation of holoprosencephaly is
      necessary for obstetricians and genetic counselors, once a prenatal diagnosis of
      holoprosencephaly has been made. We present four pregnancies in three women in
      which routine sonographic examinations led to the prenatal diagnosis of
      holoprosencephaly. Prenatal cytogenetic analysis and fluorescence in situ
      hybridization demonstrated a 46,XY,del(7)(pter-->q32:) and a
      46,XY,der(2)t(2;3)(q37;p21)pat karyotype respectively in two fetuses with
      cyclopia, and a 46,XX,der(2)t(2;3)(q37;p21)pat and a 46,XX,der(7)t(3;7)(p23;q36)
      karyotype respectively in two fetuses with premaxillary agenesis. In conclusion,
      terminal deletion 7q and partial trisomy 3p in holoprosencephalic fetuses
      indicates that genes contributing to craniofacial development reside in these
      critical regions. Proper prognostic evaluation in further pregnancies requires
      expertise in cytogenetics and genetic counseling.

PMID- 9007320
TI  - Cord blood immunoglobulin E in like-sexed monozygotic and dizygotic twins.
AB  - Genetic and environmental factors have been implicated in the etiology of atopy
      and of serum IgE levels. In order to eliminate post-natal environmental
      influences we measured IgE in cord blood (CB-IgE) from a cohort of unselected,
      like-sexed twins. IgE determination was performed with a sensitive
      radioimmunoassay with a detection limit of 0.01 kU/l. Samples with contamination
      by maternal blood were identified by IgA determination and excluded. CB-IgE was
      evaluated in 29 monozygotic (MZ) and 28 dizygotic (DZ) twin pairs. The means and
      variances for IgE values were comparable for MZ and DZ twins when sex was
      controlled for. Placental anatomy (MZ twins with mono- and dichorial placenta and
      DZ twins with one or two placentae) had no significant influence on the IgE
      levels. In an analysis of variance with sub-sampling the among-pair, within-pair
      and analytical variance components were calculated. The analytical variance was
      well below the biological variances. Biometrical analysis showed that the best
      model by Akaike Information Criteria was a model including only additive genetic
      and non-shared environmental factors. With this model the heritability estimate
      was 0.8. These data suggest that the majority of the variation in CB-IgE is
      accounted for by genetic factors, but a substantial effect of a common
      environment cannot be excluded with the present sample size.

PMID- 9007319
TI  - High frequency of new mutations in North Indian Duchenne/Becker muscular
      dystrophy patients.
AB  - Accurate carrier determination is an important aspect in providing prenatal
      diagnosis and genetic counselling to families with Duchenne/Becker muscular
      dystrophy patients. Using quantitative polymerase chain reaction, we have
      analyzed the carrier status of 31 mothers (5 familial and 23 sporadic) who have
      an affected son with known deletion in the dystrophin gene. Only four out of 23
      mothers of sporadic cases turned out to be heterozygous for the deleted exons.
      The lower number of carrier mothers in sporadic cases suggests a higher frequency
      of new mutations in North Indian DMD@BMD patients.

PMID- 9007321
TI  - Frequencies of five genetic polymorphisms in coronarographed patients and effects
      on lipid levels in a supposedly healthy population.
AB  - Allele frequencies of genetic polymorphisms were compared between supposedly
      healthy subjects and angiographically proven coronary artery disease patients.
      The polymorphic candidate loci investigated were the apolipoprotein (apo) B
      signal peptide and XbaI polymorphism, the apo E polymorphism and two polymorphism
      of lipoprotein lipase (LPL) gene: Hind/III and PvuII. Apo B signal peptide and
      HindIII/LPL polymorphisms showed significant differences in allele partition
      between cases and controls; the rare alleles of both polymorphisms were less
      frequent (p < 0.05) in cases. We looked for associations between the
      polymorphisms and lipid concentration variability in a supposedly healthy
      population (145 men and 144 women). Apo B signal peptide, apo E and PvuII/LPL
      polymorphisms seem to influence some lipid metabolism parameters significantly.
      Apo AI and LpCIII levels were significantly different among apo B signal peptide
      genotypes: Del homozygotes had the highest concentrations of both variables. The
      epsilon 4 allele of apo E polymorphism was associated with increased
      concentrations of total cholesterol, LDL cholesterol and apo B. Increased
      LpAI:AII levels observed in E3 homozygotes (p < 0.01) have not previously been
      reported. LpAI:AII concentration was also influenced by PvuII/LPL polymorphisms.

PMID- 9007322
TI  - Carrier identification of X-linked adrenoleukodystrophy by measurement of very
      long chain fatty acids and lignoceric acid oxidation.
AB  - Because identification of carriers of X-linked adrenoleukodystrophy (ALD) results
      in 5-15% false negatives with very long chain fatty acids (VLCFA) assay in
      plasma, and mutation analysis of plasma VLCFA combined with of the ALD gene is
      not always practical, we studied whether the analysis of plasma VLCFA combined
      with lignoceric acid oxidation study in fibroblasts could improve the rate of
      carrier detection. Lignoceric acid oxidation was abnormal in 19 out of 19
      patients (ALD or adrenomyeloneuropathy) and in three out of three obligate
      heterozygous women. Among ten women at risk of being a carrier, three women who
      had normal plasma VLCFA had abnormal lignoceric acid oxidation in fibroblasts.
      These data suggest that this combined biochemical procedure may help to improve
      carrier detection in families when the ALD gene mutation has not been identified.

PMID- 9007323
TI  - Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLO
      SL): a genealogical study of Swedish families of probable Finnish background.
AB  - Four Swedish families in northern Sweden with polycystic lipomembranous
      osteodysplasia (PLO-SL) were studied genealogically. Historical and genealogical
      date provided evidence for a Finnish origin. Both parents of two of the families
      could be traced back to Finnish ancestors, and the other two families had a
      common origin in a region with a known Finnish influence, but without evidence
      for Finnish ancestry. PLO-SL is the first rare monogenic disease with an
      autosomal recessive inheritance in Sweden with a probable Finnish origin.

PMID- 9007324
TI  - Genomic distribution of 5' TTCCA 3' repeat motif and its diagnostic potential in
      human Y-chromosome-related anomalies.
AB  - We have studied genomic distribution of a simple repeat motif 5' TTCCA 3' derived
      from the DYZ1 fraction of the human Y chromosome employing restriction fragment
      length polymorphism and in situ hybridization techniques. This has led us to
      develop a synthetic DNA based genetic marker specific to human genome. Randomly
      selected human genomic DNA from both sexes, digested with a total of 16
      restriction enzymes, OAT20Y probe comprising four repeat units of 5'TTCCA 3'
      motif failed to reveal fragment length polymorphisms. In contrast, with most of
      the enzymes, several multilocus monomorphic bands and with a few enzymes, smeary
      signals were detected. In situ hybridization of the OAT20Y probe with human
      chromosomes revealed grains on the long arm of the Y chromosome, whereas the X
      chromosome and autosomes showed random distribution of the grains without any
      preferential labeling in the centromeric or telomeric regions. The OAT20Y probe
      uncovers a 3.4 kb isomorphic band exclusively in the human male DNA digested with
      Hae III enzyme. Using the OAT20Y probe, we have detected the presence of Y
      chromosome in mosaic cell populations of Turner's patients with dysgenetic gonads
      and high levels of LS/FSH. The presence of Y chromosome in these patients has
      been associated with an increased risk of gonadoblastoma. The OAT20Y probe offers
      sensitivity and accuracy for the detection of Y-chromosome-bearing cells in a
      mosaic cell population and, consequently, help in better management of the
      patients.

PMID- 9007325
TI  - Routine clinical application of the FRAXA Pfu PCR assay: limits and utility.
AB  - Fragile X genotype is characterized by the excessive amplification of an unstable
      region of DNA: a trinucleotide repeat CGG of variable copy number present in the
      FRAXA locus. Methods based on polymerase chain reaction (PCR) amplification of
      the CGG repeat region could facilitate the development of a rapid screening
      assay. Unfortunately, amplification across CGG repeats can be inefficient and
      unreliable due to their 100% G + C base composition. The utility of the
      exonuclease-deficient Pfu polymerase for amplification and detection of the CGG
      repeats at the FRAXA locus has been reported. In the present study we analysed
      the utility of a Pfu PCR assay as a rapid initial screening method to rule out a
      diagnosis of fragile X syndrome in males with mental retardation. Affected males
      did not show any amplification products or a smear of amplification products
      between 350 and 550 bp. Only 10% of affected male samples did not show any
      amplification products, while the vast majority showed the amplification smear.
      The amplification smears represent a serious drawback of the method, since they
      cannot be distinguished from the amplification products of normal samples after
      separation in 1% agarose gel. Several modifications of the PCR conditions were
      attempted to eliminate this problem, but none was appropriate for clinical
      applications. However, the problem was easily solved by using a higher resolution
      electrophoretic system that allows a clear distinction of normal bands from
      pathological smears. We tested the specificity of the Pfu PCR assay, followed by
      an improved MetaPhor gel electrophoretic separation of PCR products, on 50
      samples from normal males and 24 samples form affected males. The results showed
      that this method is a rapid, sensitive and specific assay for the exclusion of
      fragile X syndrome diagnosis in mentally retarded males.

PMID- 9007326
TI  - Is intensive follow-up for early detection of tumors effective in children with
      Beckwith-Wiedemann syndrome?
AB  - Two cases of Beckwith-Wiedemann syndrome who developed malignant tumor and
      eventually died are reported. The patients followed two different screening
      programs for early detection of cancer, and the most appropriate schedule of
      follow-up in carriers of this syndrome is discussed.

PMID- 9007327
TI  - Glycerol kinase deficiency in two brothers with and without clinical
      manifestations.
AB  - We report two brothers with glycerol kinase deficiency (GKD). The older brother
      had serious clinical symptoms, mental and growth retardation, abnormal skeleton,
      spontaneous fractures and premature loss of abnormal teeth. He and his mother had
      low serum phosphate levels. He had elevated serum and urine glycerol levels and
      GKD was found in cultured fibroblasts. Prenatal diagnosis was performed in the
      second pregnancy. Glycerol kinase activity was considered normal in a chorionic
      villus sample of the foetus. After birth, it was found that the boy had elevated
      serum and urine glycerol levels. Enzymatic analysis in cultured fibroblasts
      revealed that this boy also had GKD, in spite of having no expression of the
      disease. Chromosomal analyses in the parents and both boys were normal. Major
      rearrangements or deletions were not detected in molecular studies of DNA from
      the two brothers. The hybridisation pattern was normal and no allelic loss was
      observed.

PMID- 9007329
TI  - Phenotypic characterization of a patient homozygous for the D558N LDL receptor
      gene mutation.
AB  - We describe the clinical, biochemical, and genetic features of a patient with
      true homozygous familial hypercholesterolemia due to the D558N low-density
      lipoprotein receptor gene mutation, previously designated FH Cincinnati-4.
      Functional flow-cytometric analysis of the LDL receptorR protein on upregulated
      EBV-transformed lymphocytes indicated reduction of the number of receptors on the
      cell surface by 87% and reduction of receptor activity by 89% compared to control
      cells. With drugs and a portacaval shunt operation, performed when the patient
      was 15 years old, serum cholesterol was reduced from about 28 to about 15 mmol/l.
      He died at the age of 32 of a myocardial infarction. The autopsy showed
      generalized atherosclerosis, especially in the coronary arteries, which were
      severely stenosed proximally. A rare finding was a large intracranial xanthoma
      that apparently had been asymptomatic.

PMID- 9007328
TI  - Autosomal recessive retinitis pigmentosa in Spain: evaluation of four genes and
      two loci involved in the disease.
AB  - Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous
      form of retinal degeneration. The genes for the beta-subunit of rod
      phosphodiesterase (PDEB), rhodopsin (RHO), peripherin/RDS (RDS) and the rod outer
      segment membrane protein 1 (ROM1), as well as loci at 6p and 1q, have previously
      been reported as the cause of ARRP. In order to determine whether they are
      responsible for the disease in Spanish pedigrees, linkage and homozygosity
      studies using markers at these loci were carried out on 47 Spanish ARRP families.
      SSCP analysis was performed to search for mutations in the genes cosegregating
      with the disease in particular pedigrees. Three homozygous mutations in the PDEB
      gene were found, thus accounting for 6% of the cases. No other disease-causing
      mutation was observed in the other genes analysed, nor was significant evidence
      found for the involvement of the loci at 6p or 1q. On the basis of these data, it
      is unlikely that these genes and loci account for a considerable proportion of
      ARRP cases.

PMID- 9007330
TI  - Discordant monozygotic twins with the Schimmelpenning-Feuerstein-Mims syndrome.
AB  - The Schimmelpenning-Feuerstein-Mims syndrome (SFM), characterized by linear nevus
      sebaceous and ocular and neurologic abnormalities, is a sporadic condition
      without known familial cases or etiology. We report the occurrence of SFM in only
      one of two monozygotic (MZ) twins. After considering a variety of possible
      causative mechanisms, we suggest that a postzygotic dominant lethal mutation in
      mosaic form may best explain SFM and the discordancy for SFM in these MZ twins.

PMID- 9007331
TI  - Unbalanced karyotype, dup 14(q13-q22), in a mother and her two children.
AB  - A duplication of chromosome 14(q13-q22) caused mild mental retardation and some
      dysmorphic features in two children and their mother. The unbalanced karyotype
      did not affect the fertility of the mother. Fluorescent in situ hybridization,
      with a chromosome 14 specific paint, was used to confirm that the inserted
      material was from chromosome 14.

PMID- 9007332
TI  - Short stature, moderate mental retardation, hyperactivity, facial dysmorphism,
      skeletal abnormalities, and exaggerated ketosis: a new syndrome.
AB  - We describe three siblings who presented with short stature, hyperactivity,
      delayed speech and moderate psychomotor retardation. In addition, they had
      dysmorphic features, a peculiar combination of skeletal abnormalities, small
      kidneys and exaggerated fasting ketosis. We suggest that they represent a new
      syndrome. The possibility of end-organ receptor failure is suggested.

PMID- 9007333
TI  - Report of a new case of axial mesodermal dysplasia complex.
AB  - We present a female child with phenotypical and clinical features of the axial
      mesodermal dysplasia complex. Typical manifestations of both the Goldenhar
      syndrome and the caudal regression syndrome are present in this complex. Only a
      few reports have described patients with this pattern of malformations localized
      in both the cranial and caudal regions. Our case represents a mild form of the
      complex and may contribute to a better delineation of this condition.

PMID- 9007334
TI  - Cerebral defects confirm midline developmental field disturbances in
      supernumerary der(22), t(11;22) syndrome.
AB  - We describe a girl with midline defects and distal limb anomalies, who had a
      supernumerary der(22) syndrome. The presence of some anomalies identifying the
      midline defects, led us to review all patients reported up to now, with
      interesting results. We point out the particular finding of midline defects in
      CNS only, in patients studied by autopsy or neuroradiologic imaging.

PMID- 9007335
TI  - Partial trisomy 10 mosaicism with cutaneous manifestations: report of a case and
      review of the literature.
AB  - A female infant with partial trisomy 10 mosaicism and hypomelanosis of Ito is
      presented. Features include a prominent forehead, hypertelorism, large dysplastic
      ears, prominent nasal root, a cleft lip and alveolar ridge, bilateral metatarsus
      adductus, and streaks and whorls of hypopigmented skin. The skin findings were
      diagnostic for hypomelanosis of Ito. A peripheral blood karyotype was normal.
      Fibroblasts from a junctional skin biopsy revealed mosaicism for partial trisomy
      of chromosome 10 [46, XX/47, XX, +del(10) (q11.2q23.2)]. The physical findings of
      this patient are compared to five published cases of complete trisomy 10
      mosaicism and 94 cases of isolated trisomy 10p and trisomy 10q.

PMID- 9007336
TI  - A case of pycnodysostosis with growth hormone deficiency.
AB  - Pycnodysostosis is a skeletal dysplasia characterized by short stature. Treatment
      of pycnodysostosis with growth hormone (GH) has not been reported so far. We
      describe a case of pycnodysostosis with growth hormone deficiency in addition to
      low mean insulin-like growth factor 1 (IGF-1) concentration. Complete GH
      deficiency was determined by two pharmacological provocative tests (insulin and L
      dopa). A good height-velocity response was obtained after GH replacement
      treatment. Pycnodysostosis with GH deficiency and replacement therapy have not
      been reported previously, to the best of our knowledge.

PMID- 9007337
TI  - De novo direct tandem duplication of a small segment of the short arm of
      chromosome 7 (p21.22-->22.1).
AB  - We report a boy with duplication of a small segment of the short arm of
      chromosome 7 (46,XY, dir dup (7) (p21.2-->22.1). The boy presented with
      supravalvular pulmonary stenosis, atrial septum defect and mental retardation.
      The origin of the additional material from chromosome 7 was confirmed by
      fluorescence in situ hybridization. This technique in combination with the use of
      single-copy DNA probes may in future help to delineate the phenotype/karyotype
      correlation.

PMID- 9007338
TI  - Subtle translocation (18;21) confirmed by FISH in a patient with Down syndrome.
AB  - The patient presented with the typical features of Down syndrome; hypotonia,
      brachycephaly, flattened occiput, bilateral prominent medical epicanthic folds,
      flat nasal bridge, protruding tongue, low-set dysplastic ears, short broad hands,
      bilateral clinodactyly and simian crease. The karyotype of this child was
      originally reported as normal. High-resolution chromosomes revealed extra
      material on the long arm of chromosome 18. The mother's karyotype showed a
      reciprocal translocation between the long arm of 18 and the long arm of 21 at
      band q23 and q22.1, respectively. FISH performed separately with two different
      21q cosmid probes gave two signals on the mother's metaphases and three signals
      on the proband. These findings confirmed that the proband is trisomic for the
      long arm of chromosome 21 at loci D21S65 and D21S19.

PMID- 9007339
TI  - Dinucleotide polymorphism in the first intron of the human neuronal nicotinic
      acetylcholine receptor alpha 4 subunit gene (CHRNA4).

PMID- 9007340
TI  - Nested PCR for detection of the Met235-->Thr variant of the human angiotensinogen
      gene from small volumes of serum.

PMID- 9007341
TI  - Prion diseases.

PMID- 9007342
TI  - Hyperkalemic cardiac arrest during anesthesia in infants and children with occult
      myopathies.
AB  - In 1992, the Malignant Hyperthermia Association of the United States and The
      North American Malignant Hyperthermia Registry received reports of cardiac arrest
      in apparently healthy children given succinylcholine. Using data from 1990 to
      1993, this study analyzes: (1) etiology of all reported pediatric arrests and (2)
      whether survival was associated with certain patient or treatment variables. We
      reviewed retrospectively all reports of pediatric (age < 18 years) arrests
      occurring within 24 hours of anesthesia. Etiology of arrests and presence of
      myopathy were determined. Twenty-five patients (92% male, median 45 months old)
      arrested; 23/25 (92%) were scheduled for minor surgery. Before receiving a potent
      inhalational anesthetic (92%) and/or succinylcholine (72%), these patients were
      evaluated by the anesthesiologist as being healthy with no personal or family
      history of myopathy. Serum potassium during arrest was measured in 18/25 (72%)
      patients; hyperkalemia (mean [K+] = 7.4 +/- 2.8, median 7.5 mmol/L) was detected
      in 13/18 (72%) patients. Postarrest resuscitations lasted a median of 42 minutes
      (range 10-296). Ten (40%) patients died, 1 (4%) is vegetative, and 14 (56%)
      returned to baseline neurologic function. A previously unrecognized Duchenne
      dystrophy (n = 8) or unspecified myopathy (n = 4) was diagnosed in 12 (48%)
      patients. Eight of these 12 patients' arrests were associated with hyperkalemia.
      Ten (40%) patients had no postarrest evaluation to exclude occult myopathy. No
      patient or treatment variables were statistically associated with survival. We
      conclude that, whenever possible, pediatricians should evaluate their patients
      (especially male infants and children) preoperatively for the presence of occult
      myopathy. During perianesthetic resuscitations, the pediatric advanced life
      support protocol should be modified to detect and treat hyperkalemia, a
      potentially reversible state even after prolonged resuscitation efforts.
      Following anesthetic deaths, pathologists should examine body fluid electrolytes
      and skeletal muscle for myopathy and dystrophin. If a preanesthetic creatine
      kinase screen for myopathy in male patients and restrictions on succinylcholine
      had been used, 64% of arrests and 60% of deaths might have been prevented. A
      formal prospective risk/benefit analysis for preventive measures is needed.

PMID- 9007344
TI  - Percutaneous endoscopic gastrostomy without an antireflux procedure in
      neurologically disabled children.
AB  - In children with major neurologic impairment, gastrostomies are often used to
      alleviate malnutrition and feeding difficulties. There has been a trend toward
      performing "protective" antireflux surgery in these children. Nineteen children
      with major neurologic impairment and feeding failure were prospectively evaluated
      and followed up after placement of a percutaneous endoscopic gastrostomy (PEG)
      without any antireflux procedure. Mean age at PEG placement was 34 months with
      mean follow-up of 20.7 months. All parents would recommend PEG to families with
      disabled children, and if given the chance, 95% would elect PEG again for their
      child. No child developed choking, gagging, or retching postoperatively. At the
      time of follow-up, postoperative gastroesophageal reflux did not appear to be a
      major clinical problem.

PMID- 9007345
TI  - Febrile seizures: is the EEG a useful predictor of recurrences?
AB  - We examined the predictive value of a paroxysmal EEG in children with febrile
      seizures seen at the University Pediatric Clinic, Skopje, Macedonia, between 1982
      and 1984. This was the only facility providing EEG or neurologic consultation for
      children in Macedonia, and almost all children in the area who experienced a
      febrile seizure were referred to this facility. EEGs were classified as
      epileptiform if they contained spikes and sharp waves or spike wave complexes,
      which were either focal or generalized, and were considered abnormal for age and
      state. Nonspecifically abnormal was defined as focal or generalized slowing
      excessive for age and state. Follow-up visits were scheduled at 6-month
      intervals; mean follow-up time was approximately 23 months. In order to determine
      whether clearly abnormal EEG features would predict recurrences, we compared the
      recurrences in 170 children with initial normal-appearing EEGs with 99 children
      with initial paroxysmal EEGs. There was no significant difference in risk of
      recurrence of febrile seizures between the two groups; increase in recurrence
      risk was determined primarily by younger age. The EEG did not add information
      regarding the likelihood of recurrence of febrile seizures.

PMID- 9007346
TI  - Genetic disorders associated with overgrowth.

PMID- 9007347
TI  - Microcephaly in Hurler syndrome.

PMID- 9007343
TI  - Comparison of topical anesthetics with lidocaine infiltration during laceration
      repair in children.
AB  - This study is a randomized, blinded trial that compares the effectiveness of a
      new topical anesthetic preparation of 2% mepivacaine and 1:100,000 norepinephrine
      (Mepivanor); a topical solution of 1% tetracaine, 1:4,000 adrenaline, and 4%
      cocaine (TAC); and 1% lidocaine infiltration during laceration repair in
      children. The study was conducted in the emergency department of a large academic
      children's hospital. Study participants were children 2 years of age or older
      with a laceration on the face or scalp, 5 cm or less in length, that required
      suturing. Patients were randomly assigned to receive Mepivanor topical solution,
      TAC topical solution, or lidocaine infiltration anesthesia prior to laceration
      repair. Seventy-one patients were enrolled in the study during a 2-month period.
      Outcome measures assessed pain perceptions using a Visual Analogue Scale (VAS)
      and a seven-point Likert scale. There was statistical power to detect differences
      of 1.2 to 1.7 units for the VAS outcome measures using alpha = 0.05 and beta =
      0.20. There were no statistically significant (P > 0.05) differences between TAC
      and 1% lidocaine infiltration in providing effective anesthesia. Mepivanor was
      generally less effective in providing adequate anesthesia during laceration
      repair than TAC and lidocaine infiltration, with Tukey's post hoc test for ANOVA
      demonstrating statistically significant (P < 0.05) differences between Mepivanor
      and these agents for research assistant and suture technician VAS scores. Wound
      blanching was judged to be less with Mepivanor than with TAC, although this
      difference was not statistically significant. There were no adverse reactions,
      wound infections, or healing difficulties for any of the patients who received
      TAC or Mepivanor. It was concluded that non-cocaine-containing Mepivanor was
      generally less effective than TAC and lidocaine infiltration in providing
      adequate local anesthesia during laceration repair. TAC containing only 120 mg of
      cocaine (3 mL of 4% cocaine) was as effective as 1% lidocaine infiltration in
      providing local anesthesia during laceration repair. This will allow the amount
      of cocaine in TAC to be reduced, thereby decreasing costs and the likelihood of
      adverse reactions.

PMID- 9007349
TI  - Acute dystonia following standard doses of a cold medicine containing
      phenylpropanolamine.

PMID- 9007348
TI  - Congenital factor XIII deficiency: a patient report and review of the literature.

PMID- 9007350
TI  - CPITN and the epidemiology of periodontal disease.
AB  - This paper discusses the purposes of collecting epidemiological data on
      periodontal disease, and concludes that the severe shortcomings of the CPITN
      makes it unsuited as a tool for assessing the prevalence and severity of
      periodontal disease.

PMID- 9007351
TI  - Using the DMF gender difference to assess the "major" role of fluoride
      toothpastes in the caries decline in industrialized countries: a meta-analysis.
AB  - The regular use of fluoridated toothpastes has been ascribed a major role in the
      observed decline in caries prevalence in industrialized countries during the last
      20 to 25 years, but only indirect evidence supports this claim. The purpose of
      this study was to test the hypothesis that the more frequent use of fluoride
      toothpastes by girls than by boys has reduced the relative age-specific D(M)FT
      gender difference, and that this difference should decrease with increasing age
      and fluoride toothpaste exposure among adolescents. The material comprised 8,777
      subjects 12 to 17 years of age from the pre-fluoride toothpaste era (1946-1959)
      and 39,903 from the period when use of fluoride toothpaste had become common
      (1983-1993) in industrialized countries. Meta-analyses were done using the
      relative age-specific mean D(M)FT difference between girls and boys. Separate
      analyses were carried out for subgroups of studies/countries to check for
      confounding. Regardless of analytical approach, no evidence was found to support
      the hypothesis. It is concluded that the gender difference in fluoride exposure
      due to tooth brushing frequency is too small to matter, that the study lacked
      power, or that the role of fluoride toothpastes in the caries decline has been
      overrated.

PMID- 9007352
TI  - Variations in restorative treatment decisions: an international comparison.
AB  - Variations between dentists in treatment thresholds and diagnostic decisions
      based on radiographs have not been fully explained. Since variations have been
      shown to exist between as well as within countries, it is possible that the
      structure of incentives inherent in different health care systems, and cultural
      influences on health and health care may play a part. This paper compares the
      results of a study undertaken in Scotland with a replication study undertaken in
      Canada concerning dentists' restorative thresholds and treatment decisions based
      on radiographic evidence. The Canadian dentists operated with greater sensitivity
      but lower specificity than their Scottish counterparts, although ROC analysis
      indicated similar overall abilities to detect carious lesions. The dentists'
      action thresholds also differed. However, methodological issues mean that the
      data from the study need to be interpreted with caution.

PMID- 9007353
TI  - Dental knowledge, attitudes towards oral health care and utilization of dental
      services among male industrial workers with or without an employer-provided
      dental benefit scheme.
AB  - In industrialized countries various dental benefit schemes have been implemented
      to improve the utilization of dental services, though few studies have
      demonstrated that effect. Prior to a comprehensive clinical study in southern
      Finland, a postal questionnaire survey of male industrial workers (age 38-65 yrs)
      was conducted to investigate knowledge and attitudes concerning oral health care
      and whether access to an employer-provided dental benefit scheme was associated
      with the utilization of dental services. The response rate was 81% (n = 325) in
      the subsidized group and 69% (n = 174) in the control group. In both groups, 60%
      of the subjects had had their last dental visit within a year but 91% of the
      subsidized workers compared to 79% of the controls had visited a dentist in the
      past two years (P < 0.001). The subjects had similar attitudes towards the
      importance of regular dental care and its implications for dental and general
      health. Subsidization explained the disparity in the current dental visiting
      pattern between the groups better than the possibility of using working hours for
      dental visits. Backward stepwise logistic regression revealed that the
      probability of a dental visit within the past two years was positively associated
      with access to an employer-provided dental benefit scheme, tooth brushing to
      maintain dental health, and number of teeth, and negatively associated with
      number of carious teeth. Our results demonstrate a positive impact of
      subsidization on the utilization of dental services.

PMID- 9007354
TI  - Oral impacts affecting daily performance in a low dental disease Thai population.
AB  - The aim of the study was to measure incidence of oral impacts on daily
      performances and their related features in a low dental disease population. 501
      people aged 35-44 years in 16 rural villages in Ban Phang district, Khon Kaen,
      Thailand, were interviewed about oral impacts on nine physical, psychological and
      social aspects of performance during the past 6 months, and then had an oral
      examination. The clinical and behavioural data showed that the sample had low
      caries (DMFT = 2.7) and a low utilization of dental services. 73.6% of all
      subjects had at least one daily performance affected by an oral impact. The
      highest incidence of performances affected were Eating (49.7%), Emotional
      stability (46.5%) and Smiling (26.1%). Eating, Emotional stability and Cleaning
      teeth performances had a high frequency or long duration of impacts, but a low
      severity. The low frequency performances; Physical activities, Major role
      activity and Sleeping were rated as high severity. Pain and discomfort were
      mainly perceived as the causes of impacts (40.1%) for almost every performance
      except Smiling. Toothache was the major causal oral condition (32.7%) of almost
      all aspects of performance. It was concluded that this low caries people have as
      high an incidence of oral impacts as industrialized, high dental disease
      populations. Frequency and severity presented the paradoxical effect on different
      performances and should both be taken into account for overall estimation of
      impacts.

PMID- 9007355
TI  - Attitudes to malocclusion among 18- and 35-year-old Norwegians.
AB  - Knowledge about age-related changes in attitudes to dental appearance and
      orthodontic treatment may guide the orthodontist in educating and providing
      advice to potential patients and their parents. The purpose of the present study
      was to compare attitudes to malocclusion in groups of young and middle-aged
      adults from populations having been exposed to similar provision of care. The
      material comprised samples of orthodontically untreated 18-yr-olds (n = 50) and
      35-yr-olds (n = 73) from Oslo, Norway. From a clinical examination, radiographs,
      and measurements on dental study casts, the subjects were classified according to
      the Need for Orthodontic Treatment Index (NOTI) used by the Norwegian Health
      Insurance System. Satisfaction with dental appearance and desire for orthodontic
      treatment were investigated using questionnaires. The 35-yr-olds exhibited
      significantly more malocclusion compared to the 18-yr-olds (P < 0.01). Among
      subjects classified to have obvious need for orthodontic treatment, 54% and 21%
      expressed dissatisfaction at ages 18 yr and 35 yr, respectively, indicating a
      lower level of concern for malocclusion in the older age group.

PMID- 9007356
TI  - Development of a scale to measure the social and psychological effects of severe
      dental anxiety: social attributes of the Dental Anxiety Scale.
AB  - This paper describes the development of a scale designed to measure the extent to
      which severe dental anxiety or phobia affects patients' social wellbeing outside
      of the dental setting. Items initially selected on the basis of clinical
      experience were administered to two groups: 78 patients seeking help for severe
      anxiety and 88 patients attending the general clinic of a dental hospital. Items
      on the scale discriminated between these two groups and also between patients who
      were reluctant to attend even when experiencing symptoms and those who attend
      more regularly. Although the scale correlated moderately well with Corah's Dental
      Anxiety Scale, factor analysis indicated that its items assess the effects of
      severe anxiety on the two domains of psychological reactions and social
      inhibition as they occur as indirect effects of dental care. The scale could be
      included in assessments designed to measure the social and psychological effects
      of severe dental anxiety.

PMID- 9007357
TI  - Using subjective oral health status indicators to screen for dental care needs in
      older adults.
AB  - A study was undertaken to assess the ability of a number of subjective oral
      health status indicators to identify community-dwelling older adults who need
      dental treatment. The indicators consisted of a single-item self-rating of
      treatment need, a 15-item psychosocial impact index and the 49-item Oral Health
      Impact Profile (OHIP). Data for the study were collected as part of an oral
      health survey of Canadians aged 50 years and over. The associations between these
      subjective indicators and clinically defined dental treatment needs were assessed
      using statistics for determining the predictive power of a diagnostic test.
      Although there were statistically significant associations between the subjective
      and clinical measures, values for statistics such as sensitivity, positive
      predictive values and positive likelihood ratios were low. Although the measures
      did not perform well as screening tests, they did identify a sub-group of
      individuals whose clinical conditions impacted significantly on daily life and
      who would probably benefit the most from dental treatment. In this respect, the
      subjective measures assessed here can themselves be interpreted as indicators of
      need which complement conventional clinical measures of needs for dental care.

PMID- 9007358
TI  - Incidence of root caries in an older Canadian population.
AB  - This paper reports the results of a longitudinal study of Canadians aged 50 years
      and over which was designed to estimate the three-year incidence of root caries.
      At baseline, 699 randomly selected dentate subjects were clinically examined and
      493 were examined again after three years. Over this period 27.4% had one or more
      root DFS increments and the mean DFS increment was 0.6 per person. Because DFS
      increments overstate root caries incidence DS increments were also calculated.
      Relatively few baseline variables were associated with either DFS or DS
      increments. In logistic regression analyses, age was the only variable associated
      with one or more root DFS increments, while age, dental visiting pattern and
      wearing a partial denture were associated with one or more root DS increments. In
      both cases, the predictive power of the models was poor but improved marginally
      when baseline root caries experience was also entered as an independent variable.

PMID- 9007361
TI  - Clinical determinants of a parent's satisfaction with the appearance of a child's
      teeth.

PMID- 9007362
TI  - Developmental enamel defects and extrinsic tooth stain in Libyan schoolchildren.

PMID- 9007360
TI  - Gender differences in characteristics, infection control practices, knowledge and
      attitudes related to HIV among Ontario dentists.
AB  - We surveyed 5,997 dentists in Ontario to investigate gender differences in the
      characteristics, infection control practices, knowledge and attitudes regarding
      the treatment of HIV-infected patients. The response rate was 70.3%. Reports
      indicated that female dentists are younger and more likely to work in larger
      urban centres (P < 0.00001), and in general practice (P < 0.0001) than their male
      counterparts. Multiple logistic regression analyses indicated that many
      significant gender differences in the univariate analyses could be explained by
      the confounding influence of age, practice location, and specialty; however, some
      differences remain significant: Women were more likely than men to report
      attending continuing education dealing with HIV/AIDS in the past two years (P <
      0.001), and to use masks and eye protection (P < 0.00001). Men reported more
      economic concerns than women: they were more concerned about the financial burden
      of infection control costs (P < 0.00001), and losing patients from their practice
      if it is known that they treat patients with HIV (P < 0.05). However, there were
      no significant differences in willingness to provide treatment for patients with
      HIV. We conclude that there is little evidence to show that access to oral care
      for patients with HIV is affected by gender differences.

PMID- 9007359
TI  - Caries prevalence and salt fluoridation among 9-year-old schoolchildren in
      Strasbourg, France.
AB  - The 9-year-old group (236 children) of an epidemiological study carried out in
      1991 in Strasbourg on children aged 6 to 15 years was selected with the aim of
      determining if the caries prevalence reduction observed could be related to the
      use of salt fluoridation (FS) introduced in France in 1987. From these 236
      children, 143 answered a questionnaire which showed that 36 of them were
      fluoridated salt users and 107 were not. The dft index was significantly lower in
      the FS consumers which showed 35.5% dft reduction compared to the non-FS
      consuming children. When using the Generalized Linear Model, this reduction was
      significant (P = 0.03). Although lower in the FS group, the DMFT and DMFS indices
      showed no statistical significant difference. It appeared that 72.2% of the users
      took simultaneously fluoride tablets but no dental fluorosis was observed. The
      use of fluoride tablets had a significant effect on the DMFS (P = 10(-2)). The
      children who consumed FS used more frequently fluoridated mouthrinses (P = 10(
      3)) and had more frequent professional application of fluoridated gel and
      varnishes than non-consumers (P = 0.02). The DMFS index increased with the number
      of meals (P = 10(-6)), which was the most significant variable entered into the
      Generalized Linear Model. The children who brushed their teeth once a day had a
      DMFS value 2.6 times higher than those who brushed regularly three times a day (P
      = 10(-3)). The DMFS value was 4.4 times higher among the children who brushed
      their teeth irregularly when compared with those who brushed three times a day (P
      = 10(-2)).

PMID- 9007363
TI  - Application of HSV colour system in identification by colour of biological
      objects on the basis of microscopic images.
AB  - This paper demonstrates preliminary image processing with the aim of obtaining
      invariant signs for identification by colour. For this purpose we have used
      microscopic images of cell structures in coloured peripheral blood smears. The
      main parameter for the identification is the colouring of the respective cell
      structures on the basis of which we have created histograms by hue for the
      available cell types.

PMID- 9007364
TI  - A method for fully automated quantitative analysis of arterial flow using flow
      sensitized MR images.
AB  - While the recent developments in the velocity-sensitive MR imaging offer great
      potential for non-invasive assessment of blood flow in major blood vessels, the
      clinical applications of this technique have been hampered by tedious, human
      assisted data processing techniques. In this paper, we describe a robust system
      for automated extraction of quantitative as well as qualitative flow information
      from velocity-sensitive, phase contrast MR images. The algorithm accomplishes
      reliable segmentation of blood vessels using multiresolution analysis based on
      wavelet transform, and employs a multivariate scoring criterion to minimize the
      impact of imaging artifacts such as partial volume averaging and flow turbulence,
      which normally cause incomplete or inaccurate detection of vascular boundaries.

PMID- 9007365
TI  - Magnetic resonance angiography in neck masses.
AB  - Carotid MR angiography has primarily been used to evaluate for stenotic lesions.
      We performed 2D time of flight MR angiography in 25 patients with palpable neck
      masses. There were 23 masses confirmed histologically. Two of the masses
      represented abnormal carotid arteries. Carotid deviation was seen in 23 of 25
      (92%) of patients. Widening of the carotid bifurcation was identified in seven
      patients, including four carotid body tumors, one inflammatory mass, one benign
      salivary gland tumor, and one schwannoma. Increased vascularity was identified in
      one carotid body tumor and in one metastatic papillary carcinoma of the thyroid.
      MR angiography may be useful to demonstrate flow within vessels and represents a
      familiar imaging display for surgical planning. Splaying of the carotid
      bifurcation is useful in demonstrating carotid space lesions.

PMID- 9007367
TI  - Thalamic hydatid cyst: contrast-enhanced MR imaging findings.
AB  - The case is presented of a 4-yr-old boy with a thalamic hydatid cyst. On a MR
      imaging study, the pericyst, as well as the germinal layer of the lesion,
      apparently showed enhancement after administration of the contrast medium. A few
      previous MR imaging studies on cerebral hydatid cysts described such enhancement;
      however, its mechanism was unclear. In this communication we propose a mechanism
      on enhancement of the cystic walls.

PMID- 9007366
TI  - MR findings in patients with acute tibial plateau fractures.
AB  - OBJECTIVE: The purpose of this study was to demonstrate the MRI findings
      associated with acute tibial plateau fractures. MATERIALS AND METHODS: MR scans
      of 29 patients with acute tibial plateau fractures were analyzed retrospectively.
      The images were evaluated for the presence of injuries involving the menisci,
      cruciate and collateral ligaments. The presence of a lipohemarthrosis or a simple
      joint effusion was also noted. The tibial plateau fractures were classified
      according to the scheme devised by Schatzker. RESULTS: Evidence of internal
      derangement of the knee was found in 28 (97%) patients. Tibial collateral
      ligament (55%) injuries and lateral meniscus (45%) tears were noted most
      frequently. Medial meniscus tears were seen in 21% and fibular collateral
      ligament injuries were diagnosed in 34%. Forty-one percent had anterior cruciate
      ligament injuries while the posterior cruciate ligament was injured in 28%.
      Twelve (41%) patients demonstrated the characteristic MRI features of a
      lipohemarthrosis. Simple joint effusions were found in the remaining 17 (59%)
      patients. CONCLUSION: MR imaging in patients with acute tibial plateau fractures
      commonly demonstrates associated ligamentous and meniscal injuries. By imaging in
      multiple planes, MRI can aid in the accurate characterization of tibial plateau
      fracture patterns and severity.

PMID- 9007368
TI  - Gliotic, nodular lesions in phenylketonuria: MR imaging findings.
AB  - Phenylketonuria represents one of the amino acid disorders. In this condition,
      and in other aminoacidurias, findings in MR imaging studies are generally
      nonspecific. We report a patient with phenylketonuria who had nodular lesions
      lesions associated with the usual deep white matter involvement seen in the
      condition. We suggest that these nodular lesions may represent foci of gliotic
      tissue, as previously shown by neuropathological studies on phenylketonuria.

PMID- 9007369
TI  - CT appearance of the Syed-Neblett device for interstitial brachytherapy of
      gynecologic malignancies.
AB  - Radiation therapy is an important adjuvant treatment for gynecological
      malignancies. However, the maximum amount of radiation treatment is limited by
      the side effects to the normal local tissue. We present a brief summary of the
      use and appearance of the Syed-Neblett intracavitary device. This device allows
      delivery of radioactive implants to a local tumor resulting in maximum dosage to
      tumor tissue, but limiting dosage to the surrounding normal tissue.

PMID- 9007370
TI  - Nickel dermatitis: how much nickel is safe?
AB  - The Nickel Directive will become law in the countries of the European Union in
      1996. This directive states that the concentration of nickel in post assemblies
      (used after ear piercing) may not exceed 0.05%, that products which come into
      direct and prolonged contact with the skin, e.g. earrings, watchstraps or
      zippers, may not release greater than 0.5 microgram/cm2/week, and that nickel
      release from coated products will not exceed this level after 2 years of normal
      use. The data relating to the threshold for reacting to nickel and the levels of
      nickel release from nickel-containing objects, are considered in this review.
      Although the level of 0.5 microgram/cm2/week is one below which a minority of
      nickel-allergic subjects will react, it is not safe in every nickel-sensitive
      individual. This level of nickel release is currently exceeded by many nickel
      containing alloys and jewelery items that are made from high-sulfur stainless
      steel, and manufacturers are going to have to change the composition of jewelery
      to comply with the directive.

PMID- 9007371
TI  - Airborne contact dermatitis from unexpected exposure to rosin (colophony). Rosin
      sources revealed with chemical analyses.
AB  - We report 3 cases of contact dermatitis in rosin-sensitive individuals caused by
      exposure to airborne rosin components from different sources. Case no. 1 was a
      female office worker with a facial dermatitis caused by rosin components which
      emanated from the linoleum floor covering in her office. Floor material
      containing wood flour and rosin was released into the air, causing a facial
      dermatitis in the rosin-sensitive subject. Case no. 2 involved a woman who worked
      in a factory producing dairy product cartons and had a dermatitis on her lower
      legs, lower arms and upper chest. Her dermatitis was caused by dust from the
      paper cartons and contact allergy to rosin components probably aggravated her
      dermatitis. Case no. 3 was a female office worker with a relapsing dermatitis on
      her eyelids. Her dermatitis was caused by a rosin-containing floor polish, which
      was seen as a powder on the office floor. Extracts of suspected material and
      products were patch tested and analysed for the presence of rosin components with
      HPLC and GC techniques. A discussion and recommendations on chemical analyses of
      rosin components follow. We conclude that a thorough investigation, including
      chemical analyses, can rule out non-specific diagnoses and offer a solution to
      the patient's skin problems.

PMID- 9007372
TI  - Suboptimal non-inflammatory concentrations of haptens may elicit a contact
      sensitivity reaction when used as a mix.
AB  - Contact dermatitis is a cutaneous inflammatory reaction mediated by hapten
      specific T cells. We used a murine model to investigate the contact sensitivity
      reaction elicited by different concentrations (optimal and suboptimal) of the
      haptens DNFB and oxazolone applied singly or in combination. The simultaneous
      application of DNFB and oxazolone at optimal concentrations (0.2% and 0.4%
      respectively) did not significantly increase the ear swelling response induced by
      each of the allergens when applied singly. No contact sensitivity response was
      observed when the haptens were tested individually at subthreshold concentrations
      (0.05% and 0.1% respectively). However, mixing the 2 molecules at the same
      concentrations gave rise to a clinical contact sensitivity reaction. The
      simultaneous application of the haptens at a 2 x higher, but still suboptimal
      concentrations (0.1% and 0.2% respectively), elicited an inflammatory response
      that was significantly greater than the responses elicited by either of the
      haptens when applied separately. These results suggest that a "false-positive"
      reaction to a mix may reveal a genuine sensitization to the constituents.

PMID- 9007373
TI  - Multiple sensitivities to transition metals: the nickel palladium reactions.
AB  - Patch test data of 1000 consecutive patients sensitive to at least 1 substance of
      our standard series showed that transition metals gave associated reactions
      amongst themselves more frequently than they did with the remaining substances.
      The responses to transition metals were largely variable and seemed dependent not
      only upon the associated exposure to different metals or the concomitant
      responses of the T cell clones, as reported by others, but also upon the chemical
      properties of the metals and the consequent interactions inside the skin.
      Concomitant reactions to nickel sulfate and palladium chloride were the most
      frequently found associated positivities and occurred in a minority of nickel
      sulfate-sensitive subjects. In 43 out of 45 of these subjects, patch tests to
      mixed solutions containing nickel sulfate, plus sulfates of magnesium, zinc, and
      manganese at higher doses, were not able to reduce the nickel sulfate reactions.
      This behaviour contrasted with that found in the majority of subjects sensitive
      only to nickel sulfate. These findings seem to demonstrate that, whilst in
      subjects with positive reactions to nickel sulfate alone antigen formation
      involves biomolecules containing ions, in those with concomitant reactions to
      palladium chloride, other structures are involved.

PMID- 9007374
TI  - Contact dermatitis from fatty alcohols.
AB  - The aim of this study was to investigate the frequency of sensitization to fatty
      alcohols in a group of patients with suspected cosmetic or medicament contact
      dermatitis. From May 1992 to September 1995, we patch tested a series of 5 fatty
      alcohols on 146 patients. These included 108 females and 38 males aged from 13 to
      72 years (mean age 42.5). These patients, who had previously been tested with the
      GIRDCA standard series, were selected because their clinical lesions or histories
      indicated topical preparations as the possible source of their contact
      dermatitis. High-grade fatty alcohols (> 99% pure) were used for testing. 34
      patients (23.2%), 25 female and 9 male aged from 14 to 72 years, showed a
      positive patch test to fatty alcohols, 33 of them to oleyl alcohol. A total of 39
      reactions were detected with 5 patients showing more than 1 positive reaction.
      Our results show that sensitization to oleyl alcohol is not rare in patients with
      contact dermatitis due to cosmetics or topical medicaments.

PMID- 9007375
TI  - Patch testing with allergens from modified rosin (colophony) discloses additional
      cases of contact allergy.
AB  - Most rosin (colophony) used today is chemically modified. Will contact allergy to
      modified rosin be overlooked when testing is performed with only unmodified rosin
      in the standard series? 2 components from modified rosins, maleopimaric acid
      (MPA) and glyceryl I-monoabietate (GMA), earlier identified as contact allergens,
      were added to the patch test standard series. Some commonly-used modified rosin
      products were also tested. Positive reactions were observed to the modified
      components MPA and GMA. Of the patients with positive reactions to MPA and GMA,
      several did not react to unmodified rosin in the standard series. No reaction was
      observed to the modified rosin products without a concomitant reaction to
      unmodified rosin. The positive reactions observed to the modified rosins may be
      due to residual unmodified material in the product, but a possible contribution
      from allergenic modified rosin components cannot be disregarded. When a patient's
      history indicates a rosin allergy, but a negative response to unmodified rosin in
      the standard series is observed, additional testing with GMA and MPA or, second
      best, with glycerol-esterified rosin and maleic-anhydride-modified rosin is
      recommended. Some modified rosin products, which could be used for additional
      testing, are suggested.

PMID- 9007376
TI  - Occupational contact dermatitis from propacetamol.
AB  - We report 4 cases of contact sensitization to propacetamol. They presented with
      lesions on the hands, forearms, crease of the elbows, and neck. They were all
      sensitized to multiple allergens and 2 of them were atopic. Patch tests to Pro
      Dafalgan and propacetamol were positive; sodium citrate and paracetamol were
      negative. Our cases were similar to those published for the first time by Barbaud
      in 1995. The only allergen was propacetamol; patch tests with diethyglycine and
      paracetamol were negative. Propacetamol chlorhydrate is composed of a complex
      paracetamol-diethylglycine, which probably acts like a hapten capable of inducing
      cutaneous allergy. It is an occupational allergy affecting nurses who work in
      surgery departments or post-anesthesia recovery rooms, where high doses of
      analgesics are widely used. The patients were not allergic to oral paracetamol.
      Despite the usual precautions, the mixture of propacetamol chlorhydrate and
      solvent leaks onto the nurses' hands, suggesting that health care workers
      handling propacetamol chlorhydrate should wear gloves.

PMID- 9007377
TI  - Allergic contact dermatitis from benzalkonium chloride used as a denaturant of
      ethanol.

PMID- 9007378
TI  - Evaluation of the patch test results with standard antigens in various types of
      eczema.

PMID- 9007379
TI  - Occupational contact dermatitis from propranolol, hydralazine and
      bendroflumethiazide.

PMID- 9007381
TI  - Occupational allergic contact dermatitis from disinfectant wipes used in
      dentistry.

PMID- 9007380
TI  - Airborne allergic contact dermatitis from tea tree oil.

PMID- 9007382
TI  - Allergic contact dermatitis from disodium ricinoleamido MEA-sulfosuccinate in
      shampoo.

PMID- 9007383
TI  - Comparison of 2 different methods for enhancing the reaction to nickel sulfate
      patch tests in negative reactors.

PMID- 9007384
TI  - Cow dander: the most common cause of occupational contact urticaria in Finland.

PMID- 9007385
TI  - Contact dermatitis to Dendranthema morifolium (Ramat).

PMID- 9007386
TI  - Diphenhydramine: a forgotten allergen?

PMID- 9007387
TI  - Delayed hypersensitivity reaction to the non-ionic contrast medium iopromid.

PMID- 9007388
TI  - A study of 5 newly patch-tested reactive textile dyes.

PMID- 9007389
TI  - Bullous pemphigoid mimicking contact dermatitis.

PMID- 9007390
TI  - Allergic contact dermatitis from Euxyl K 400 in a sunscreen cream.

PMID- 9007391
TI  - Patch testing in suspected allergic contact dermatitis due to Emla cream in
      haemodialyzed patients.

PMID- 9007392
TI  - Airborne contact dermatitis from metaproterenol in a respiratory therapist.

PMID- 9007393
TI  - The chemical structure of the rubber chemical cyclohexyl thiophthalimide.

PMID- 9007394
TI  - Non-specific hyperreactivity related to the use of Freund's complete adjuvant.

PMID- 9007395
TI  - Brain tumor therapy in the third millennium.

PMID- 9007396
TI  - Current treatment of meningiomas.
AB  - Intracranial meningiomas continue to challenge our best clinical efforts at
      eliminating the tumors once discovered and deemed appropriate for treatment.
      Molecular biological clues about the role of hormones in the development and
      progression of meningiomas might assist with treatment in the future. Physical
      therapies with surgical removal and irradiation have almost reached their
      technical limits. Important articles on advances in these areas are summarized.

PMID- 9007397
TI  - Current treatment of cerebral metastasis.
AB  - Brain metastasis from systemic cancer remains a significant source of morbidity
      and mortality. Current treatment modalities include surgery, whole brain
      radiation, radiosurgery, brachytherapy, chemotherapy, and other experimental
      methods such as hyperthermia, hormonal therapy, and the use of biological
      modifiers. In this article we review and evaluate recent developments in these
      treatment modalities for the management of cerebral metastasis.

PMID- 9007398
TI  - Current diagnosis and treatment of central nervous system germ cell tumours.
AB  - Central nervous system germ cell tumours can be cured with high quality
      posttreatment neuropsychological and endocrinological measures. In order to
      firmly establish a histological diagnosis, surgery is essential. Management
      should be planned precisely according to histological and biological malignancy
      and the extent of the disease. Patients with germinoma can be cured by
      preirradiation chemotherapy followed by reduced dose irradiation.

PMID- 9007399
TI  - Epilepsy in patients with central nervous system tumors.
AB  - Seizure is often the first manifestation of a central nervous system tumor; such
      tumors are often responsible for pharmacologically refractory seizures. The
      treatment of tumor-associated epilepsy should, on one hand, follow sound neuro
      oncological principles and, on the other hand, control the epilepsy.

PMID- 9007400
TI  - Metabolic imaging in the diagnosis of brain tumors.
AB  - Positron emission tomography, single photon emission computed tomography and
      magnetic resonance spectroscopy provide distinct, uncorrelated and sensitive
      indicators of brain tumors which can be used to improve differential diagnosis,
      biopsy guidance or therapy monitoring. New findings, including conflicting ethyl
      cysteinate-dimer/hexamethyl-propyleneamineoxide uptake in single photon emission
      computed tomography and increased lipids and macromolecules in magnetic resonance
      spectroscopy, may provide new tools for the investigation of clinical tumors.

PMID- 9007401
TI  - Rehabilitation of progressive neurological disorders: a worthwhile challenge.

PMID- 9007402
TI  - Physician and patient-oriented outcomes in progressive neurological disease:
      which to measure?
AB  - Outcomes can be described as either physician or patient-oriented depending on
      whose perspective is adopted. Both perspectives offer different yet complementary
      information. Traditionally, the effectiveness of interventions has been evaluated
      in terms of physician-oriented outcomes. recently there has been a growing
      recognition of the importance of the patient's point of view in assessing the
      outcomes of medical care. This is now held to be central to the monitoring and
      evaluation of health care. This review describes these two perspectives and
      compares the nature of the information provided by each.

PMID- 9007403
TI  - Is electrostimulation preferable to surgery for upper limb ataxia?
AB  - Ataxic syndromes of the upper limbs are observed in various situations but are
      usually a result of lesions involving the efferent pathways of the cerebellum,
      the superior cerebellar peduncles and midbrain. The commonest causes are multiple
      sclerosis, brain injury and focal neoplastic or vascular lesions. Cerebellar
      tremor, which usually comprises a postural and intentional component, is the
      commonest clinical form. In this review, we assess the value of the various
      surgical techniques in the treatment of this particular form of ataxia of the
      upper limbs.

PMID- 9007405
TI  - Mechanisms and management of fatigue in progressive neurological disorders.
AB  - Fatigue in neurologic disorders has been examined in several important studies
      over the past year. These reports suggest that fatigue is a common and often
      profoundly debilitating symptom. Assessment and treatment of fatigue requires a
      multidisciplinary approach.

PMID- 9007404
TI  - Reflex hyperexcitability and muscle contracture in relation to spastic
      hypertonia.
AB  - Mechanisms of spasticity and possible therapeutic interventions continue to
      dominate research into motor disorders following cerebral lesions. However, the
      accumulated evidence suggests that this focus on spasticity may be out of step
      with its effects. In contrast, hypertonia remains an important problem. Further
      investigation into its link with muscle contracture is required and it needs to
      be clearly distinguished from reflex hyperexcitability in patients with
      spasticity.

PMID- 9007406
TI  - Virtual reality: an assistive technology in neurological rehabilitation.
AB  - The need for improved neurological rehabilitation strategies is self-evident.
      Recent developments in the computer technology of virtual reality hold the
      promise of exciting progress in this area. In this paper four areas of potential
      application of virtual reality to neurological rehabilitation are reviewed.

PMID- 9007407
TI  - Cellular models for pathogenesis in mitochondrial diseases.

PMID- 9007408
TI  - Pathogenetic mechanisms in peroxisomal disorders.
AB  - Advances have been made concerning the pathogenesis of the two major classes of
      peroxisomal disorders. The gene defect in X-linked adrenoleukodystrophy has been
      firmly established and therapies are emerging. Complementation analysis has
      permitted categorization of disorders of peroxisome biogenesis, their molecular
      basis and mutations are being defined, and new therapies are being explored.

PMID- 9007409
TI  - Fatty acid mitochondrial beta-oxidation and hypoglycaemia in children.
AB  - Mitochondrial fatty acid beta-oxidation is a major source for energy production,
      particularly at times of stress or fasting. Inborn errors of fatty acid oxidation
      have emerged during the past decade as important inherited causes of severe
      metabolic disturbances, including hypoketotic hypoglycaemia, cardiomyopathy,
      skeletal muscle myopathy, and childhood sudden death. Since the first description
      in 1973, at least 14 different genetic defects of mitochondrial fatty acid
      metabolism have been recognized. Our current understanding of the basic
      biochemistry, clinical presentations, and molecular bases of fatty acid oxidation
      disorders is reviewed.

PMID- 9007410
TI  - Superoxide dismutase and oxygen radical neurotoxicity.
AB  - Although reactive oxygen species are natural metabolic products, they can be
      toxic to cells and are implicated in some neurodegenerative disease. Cytosolic
      Cu, Zn superoxide dismutase normally defends against damage by reactive oxygen
      species; however, mutant forms of the enzyme might instead contribute to damage
      of motor neurons n some amyotrophic lateral sclerosis patients. Possible
      mechanisms of oxidative injury to neurons are discussed with reference to
      cytosolic Cu, Zn superoxide dismutase mutations and other factors which might
      enhance oxygen radical toxicity.

PMID- 9007412
TI  - Neoplasms.

PMID- 9007413
TI  - Trauma and rehabilitation.

PMID- 9007411
TI  - Neurotoxicity of beta-amyloid and prion peptides.
AB  - Neuropathological observations, supported by genetic and biochemical studies,
      indicate the central role of amyloid-beta protein deposits in the pathogenesis of
      Alzheimer's disease. In prion-related encephalopathies also, an altered form of
      prion protein forms amyloid fibrils and accumulates in the brain. In both
      conditions the amyloid deposition is accompanied by nerve cell loss, the
      pathogenesis and molecular basis of which are not understood. Synthetic peptides
      homologous to amyloid-beta protein and its fragments and to prion protein
      fragments are utilized to investigate the mechanisms of cerebral deposit
      formation and the role played by these proteins in Alzheimer's disease and prion
      related encephalopathies, respectively. Amyloid-beta protein peptides have been
      shown to be neurotoxic and amyloidogenic under experimental conditions and
      numerous studies have been performed to clarify the mechanism of neuronal death
      induced by exposure to these peptides. Peptides homologous to the fragment 106
      126 of prion protein, an integral part of all abnormal prion protein isoforms
      that accumulate in the brain of patients with prion-related encephalopathies, are
      neurotoxic, fibrillogenic, and have a secondary structure largely composed of
      beta-sheet and proteinase-resistant properties.

PMID- 9007414
TI  - Metabolic disorders and neurotoxicology.

PMID- 9007415
TI  - Disablement observed, addressed, and experienced: integrating subjective
      experience into disablement models.
AB  - Although subjective experience is critical to full comprehension of disablement,
      it has yet to be integrated into models in a systematic and theoretically
      grounded way. This article presents a framework for modelling disablement that
      includes both objective and subjective features. The framework is based on a
      novel integration of: (1) perspectives on disablement; (2) the contexts within
      which disablement occurs; and (3) interaction among these perspectives and
      contexts. The framework is developed using nomenclature derived from the WHO's
      International Classification of Impairments, Disabilities, and Handicaps (ICIDH).
      Although ICIDH terminology is used, the article's integration of ideas can as
      well be applied to other disablement nomenclatures and models. The framework
      offers a conceptual background for innovative clinical, policy, and research
      responses to disablement, as well as for further development of disablement
      theory and models.

PMID- 9007416
TI  - The relationship between age, gender and psychological distress in rehabilitation
      inpatients.
AB  - Although commonly accepted as the dominant emotional reaction to functional loss,
      the reported occurrence of depression in rehabilitation patients varies widely.
      Rather than focusing solely on depressive symptoms, this study furthers our
      understanding of emotional distress following a functional loss by assessing a
      range of psychiatric symptoms. A series of rehabilitation patients admitted to an
      urban hospital inpatient unit is used as the sample (n = 48). Demographic,
      neuropsychological, and a functional independence measure were included as
      independent variables. The statistical analysis revealed that-although age was
      not correlated with years of education, functional status, or neuropsychological
      impairment-there was a significant inverse relationship between age and reported
      emotional distress. Utilizing MANCOVA to explore the impact of age and gender on
      specific groups of psychiatric symptoms revealed that both younger and male
      patients tended to express psychiatric symptoms more frequently. The importance
      of considering age and gender in evaluation of emotional distress in
      rehabilitation is supported in this comprehensive study of psychiatric symptoms.

PMID- 9007417
TI  - An estimation of the functional disability burden in elderly Chinese age 70 years
      and over.
AB  - A cross-sectional survey of functional status among elderly Hong Kong Chinese
      aged 70 years and over was carried out to estimate the current burden of
      disability. Two thousand and thirty-two subjects (999 men, 1033 women) were
      recruited by random sampling of the old age and disability allowance schemes
      covering over 90% of the elderly population, stratified by sex and 5-year age
      groups. Functional ability was administered using the Barthel Index. The duration
      of disability, if any, was also noted. The prevalence of disability for different
      activities of daily living varied from 0.8% to 26% (lowest for feeding and
      highest for climbing stairs and bathing). The prevalence was higher for women
      than men, and higher in the older age group for both sexes. Men in the 80+ age
      group had shorter duration of disability compared with those in the 70-79 age
      group, and compared with women. Using disability years (estimated number of
      elderly with disability in the population x median duration of disability) as an
      estimate of disability burden, the number ranges from approximately 19,000
      (inability to feed) to 100,000 (inability to climb stairs). This estimate may be
      useful in the planning of service provisions for the formal and informal care
      sector.

PMID- 9007418
TI  - The Work Rehabilitation Impact Quotient: a tool to assess the effectiveness of
      early rehabilitation of injured workers.
AB  - The Work Rehabilitation Impact Quotient (WRIQ) compares the percentage of long
      term claimants in a classification group with the percentage of long term
      claimants overall in the scheme, a value greater than one indicating that more
      people than expected remain on compensation. We studied the Accident
      Rehabilitation and Compensation Insurance Corporation of New Zealand (ACC) claims
      from 1988 to 1994 and data from the 1986 and 1991 census. High WRIQs were found
      in workers over the age of 50, people injured in motor vehicle crashes, those
      with head and multiple location injuries, and those with amputations,
      dislocations, injuries to internal organs, and OOS (Overuse syndromes). Analysis
      by occupation and industry identified certain groups with high and very high
      WRIQs. The WRIQ value was not related to the rate of injury or to job
      availability, but was related to mean claim cost. Thirty six percent of claim
      costs paid in 1994 were in groups with high or very high WRIQs. Reduction of the
      WRIQ in these groups to low levels would produce savings of over $100 million in
      1994 dollars.

PMID- 9007419
TI  - Why cardiac patients do not follow the nutritionist's advice: barriers in
      nutritional advice perceived in rehabilitation.
AB  - The aim of the present study was to identify reasons why cardiac patients do not
      follow nutritional advice which is given during rehabilitation. Barriers or
      expected problems in nutritional advice perceived during rehabilitation were
      obtained via a structured interview. Forty-eight cardiac patients (41-82 years;
      15 females, 33 males) were interviewed during rehabilitation. The majority of
      patients (54%) reported one or more barriers. The most frequently reported
      barriers were associated with situations in which the patients were eating in
      company (52%), or in which there was too much food available (44%). Another
      common reason for non-compliance was that healthy foods did not taste good (42%).
      On the other hand, barriers were seldom associated with disinterest (4%) or lack
      of knowledge (4%). These results indicate that non-compliance in nutritional
      counselling may be associated with emotional responses related to eating and with
      lack of social skills to manage eating in social situations.

PMID- 9007420
TI  - Worker assessment for future back disability using prediction factors.
AB  - The prevalence and economic cost of the low-back pain problem hardly needs to be
      mentioned in this journal. Disability ensuing from bouts of low-back pain claims
      a significant proportion of payments by Worker's Compensation Boards and national
      treasuries. Any attempt which may enhance our understanding of any aspect of this
      debilitating affliction, and perhaps more so its predictive capability, will go a
      long way towards optimization of management strategies. These management
      strategies, when refined and properly implemented, will have the potential not
      only of reducing the cost, but also of enhancing the health and safety of
      workers.

PMID- 9007421
TI  - Sexual equality: how enlightened have we become?
AB  - This paper presents a personal perspective on sex and disability. It considers
      the extent to which society has and can come to terms with the sexual needs of
      those with disabilities.

PMID- 9007422
TI  - Dickens and disability.
AB  - The novels of Charles Dickens include many vivid portraits of individuals with
      physical disabilities or deformities, and these conditions are often used
      symbolically to highlight some of the author's recurring themes. Disabled
      children are depicted as innocent victims, while their older counterparts are
      most often viewed as corrupt victimizers whose physical deformities are outward
      manifestations of their inner depravity. Punishment for moral failings in non
      disabled characters frequently takes the form of paralysis and/or aphasia
      resulting from a cerebrovascular accident. In this context the wheelchair becomes
      a potent metaphor of imprisonment as a form of retributive justice.

PMID- 9007423
TI  - Transfer of spatial information from a virtual to a real environment in
      physically disabled children.
AB  - A group 10 severely physically disabled children explored a to-scale computer
      simulation of a real multi-storey building. Following exploration, their
      knowledge of the spatial properties of the real environment was assessed by
      asking them to point to fire apparatus that was not visible from the test site.
      Subjects in a control group were asked to complete the same assessment tasks, but
      without the opportunity to explore either the real building or the computer
      simulation. The estimates of the disabled children were superior to the control
      group indicating good transfer of spatial knowledge. Route finding and
      recognition reports provided support for the pointing data in indicating good
      transfer of spatial information.

PMID- 9007424
TI  - The relationship of knee muscle performance and gait in stroke patients.

PMID- 9007425
TI  - Short-term effects of variceal sclerotherapy on portal hypertensive gastropathy.
AB  - BACKGROUND AND STUDY AIMS: Obliteration of esophageal varices may modify the
      mucosal perfusion of the stomach. The relationship between short-term injection
      variceal sclerotherapy (IVS) and the evolution of portal hypertensive gastropathy
      (PHG) is insufficiently recognized. PATIENTS AND METHODS: Forty-one cirrhotic
      patients were treated with hemostatic or secondary preventive IVS. They underwent
      sclerotherapy at intervals of four to five days until esophageal ulceration,
      stricture, or a reduction in variceal size developed. On admission and on
      completing the IVS schedule, an endoscopy score was calculated using a system
      assigning 0 points for a normal mucosal image, 1 point for reddened, 2 points for
      a mosaic-like mucosal pattern, and 3 points for a mosaic-like pattern plus red
      marks in the stomach. All patients received propranolol after the first
      sclerotherapy session. RESULTS: The total score before IVS was 45 points (1.1
      points per patient). After 188 sclerotherapy sessions (2-8 per patient), the
      score significantly increased to 73 points (1.8 points per patient, P = 0.04).
      This effect was particularly marked in Child-Pugh class B patients (mean
      individual rise from 0.7 to 1.9 points, P = 0.01), and negligible in patients
      with either less or more advanced cirrhosis (Child-Pugh classes A and C).
      CONCLUSIONS: In patients with cirrhosis, short-term IVS may contribute to the
      mechanisms of progressive PHG.

PMID- 9007426
TI  - Experimental evaluation of the optimal in-vitro conditions for bipolar
      electrocoagulation in the bile duct.
AB  - BACKGROUND AND STUDY AIMS: Although there have been many reports concerning the
      therapeutic use and potential of laser and monopolar electrocoagulation therapy,
      little has been published on the effects of bipolar electrocoagulation on biliary
      tissue. Although it has been reported that endoscopic recanalization of malignant
      stent obstruction using bipolar electrocoagulation is an advantageous form of
      treatment, the optimal parameters for this type of treatment have not yet been
      determined. The purpose of this prospective study was therefore to evaluate,
      under in-vitro conditions, the maximum applicable energy required; the influence
      of probe angle and duration time on the extent of the coagulation achieved; and
      whether multiple intermittent short pulses show any significant differences in
      the extent of coagulation achieved, in comparison with the use of a single
      continuous pulse. PATIENTS AND METHODS: In this in-vitro study, experiments were
      carried out in 84 common bile ducts from freshly slaughtered swine. The extension
      of tissue injury after electrocoagulation treatment was measured at 60
      combinations of varying levels of power output, probe angles, duration times, and
      pulse patterns. All of the results were correlated with the diameter of the
      untreated and normal bile duct walls under in-vitro conditions. RESULTS: When
      energy was applied at levels up to a maximum of 16 J, the extension of tissue
      coagulation was about 58% of the untreated bile duct wall diameter. Energy
      settings exceeding 16 J involved the whole wall diameter in most cases, often
      including the periductal fatty tissue. Additional energy applications higher than
      16 J, 32 J, and 100 J, showed undesirable tissue changes, such as an increasing
      diameter in the treated bile duct walls of up to 56.8% of the wall diameter of
      control specimens. CONCLUSIONS: The study evaluated the standard settings in an
      in-vitro model. The results indicate that protective and effective use of bipolar
      electrocoagulation on normal porcine bile duct tissue requires: the use of a low
      power setting (less than 16 J); the use of continuous short pulse patterns;
      placement of the probe tip at an obtuse angle (0 degree); and the use of short
      application times.

PMID- 9007427
TI  - Biliary endoprosthesis as an alternative to endoscopic nasobiliary drainage in
      patients with acute cholangitis.
AB  - BACKGROUND AND STUDY AIMS: Conventionally, acute cholangitis is managed by
      placing a nasobiliary drainage catheter. We have attempted to place a biliary
      endoprosthesis in such patients as an alternative to using nasobiliary catheter
      drainage. PATIENTS AND METHODS: Twenty-seven patients with acute cholangitis were
      managed by placement of 7-Fr straight biliary endoprostheses instead of using
      nasobiliary drainage catheters to decompress the biliary system. The procedure
      was carried out without sphincterotomy and without image intensification.
      RESULTS: Biliary endoprosthesis placement was successfully carried out in all the
      patients. Definitive treatment was then provided to all but four patients, who
      either had inoperable cancer or were at high risk for surgery. Early stent
      occlusion occurred in one patient, and in another patient the Dormia basket
      became entrapped while stones were being removed from the common bile duct. There
      were no mortalities. CONCLUSIONS: Biliary endoprosthesis placement is safe, easy
      to perform, and is a cheaper alternative to endoscopic nasobiliary drainage.

PMID- 9007428
TI  - Assessment of tumor invasion of the distal esophagus in carcinoma of the cardia
      using endoscopic ultrasonography.
AB  - BACKGROUND AND STUDY AIMS: Esophageal invasion by carcinoma of the cardia may
      affect the surgical approach. Accurate assessment of esophageal invasion is
      difficult using endoscopy, computed tomography, or barium contrast radiography.
      The aim of the present study was to evaluate the use of endoscopic
      ultrasonography (EUS) in the prediction of esophageal invasion by carcinoma of
      the cardia. PATIENTS AND METHODS: EUS (using a linear-array scanner) was carried
      out prospectively in 47 patients with carcinoma of the cardia who underwent
      subsequent surgical resection. The findings were correlated with the
      histopathological assessment of tumor infiltration in the esophagus in the
      resected specimen. RESULTS: An absence of esophageal invasion was correctly
      predicted by EUS in 12 of 13 patients. Histopathologically confirmed invasion of
      the esophagus was correctly predicted in 32 of 34 patients. With a margin of
      error of 10 mm, the accuracy of EUS in predicting or excluding histologically
      confirmed invasion of the esophagus was 85.1% (40 of 47 patients). False-positive
      results with EUS occurred in patients with prominent edematous or fibrous changes
      in the distal esophagus; false-negative results with EUS were seen in patients
      with scattered infiltration of a small number of tumor cells into the mucosal or
      submucosal layer. CONCLUSIONS: EUS can provide the surgeon with additional
      information on the extent of esophageal infiltration in patients with carcinoma
      of the gastric cardia, and can therefore assist in the selection of the surgical
      approach.

PMID- 9007429
TI  - Injection of fibrin tissue adhesive versus laser photocoagulation in the
      treatment of high-risk bleeding peptic ulcers: a controlled randomized study.
AB  - BACKGROUND AND STUDY AIMS: A controlled and randomized multicenter study was
      carried out in order to compare the efficacy of fibrin sealant and Nd:YAG laser
      photocoagulation in patients with high-risk arterial bleeding from peptic ulcers
      of the stomach and the small intestine. PATIENTS AND METHODS: In four teaching
      hospitals, 53 patients presenting with either active arterial ulcer bleeding
      (Forrest class 1 a) or a large visible vessel in the ulcer base (diameter over 2
      mm, Forrest class 2 a) were treated with infiltration of epinephrine 1: 10,000
      followed by the injection of fibrin tissue adhesive (n = 28), or with epinephrine
      plus laser photocoagulation (n = 25). Permanent hemostasis for at least seven
      days served as the principal end point; rebleeding, emergency surgery, and
      hospital mortality served as further end points. RESULTS: There were no
      significant differences between the study groups in terms of age, risk factors,
      initial hemoglobin values, number of patients showing signs of hemodynamic
      impairment, ulcer size and localization, or bleeding activity. Primary hemostasis
      was achieved in all patients. Rebleeding rates were seven of 28 and four of 25
      among the patients treated with fibrin sealant and laser coagulation,
      respectively (not significant). There were no significant differences regarding
      the rates of ultimate hemostasis (24 of 28 vs. 24 of 25), emergency surgery (four
      of 28 vs. one of 25), or hospital mortality (0 vs. two of 25). No complications
      occurred with either form of treatment. Patients who had a visible vessel in the
      ulcer floor at the first control endoscopy had a significantly higher incidence
      of rebleeding, regardless of the type of endoscopic therapy. CONCLUSIONS: We
      conclude that both the injection of fibrin tissue adhesive and laser
      photocoagulation are effective methods of treating high-risk arterial peptic
      ulcer bleeding. As the number of high-risk patients necessary to reach
      significance are difficult to recruit within a reasonable period even in a
      multicenter study, a new meta-analysis of all studies now available should be
      considered.

PMID- 9007430
TI  - Cancer surveillance in ulcerative colitis: a survey of patients' knowledge.
AB  - BACKGROUND AND STUDY AIMS: The present study aimed to investigate the level of
      knowledge concerning colorectal carcinoma and its screening and treatment in a
      group of patients with long-standing and extensive ulcerative colitis. PATIENTS
      AND METHODS: A postal questionnaire was sent to 61 patients with long-standing
      and extensive ulcerative colitis. They were asked about their risk of carcinoma,
      about the existence of screening facilities, and about the treatment of
      colorectal carcinoma. RESULTS: Forty-three completed questionnaires were
      returned. Eighty-six per cent of patients were aware of the increased risk of
      carcinoma. Only 44% knew that it was possible to screen for colorectal carcinoma.
      Forty-seven per cent of patients were unaware that carcinoma detected at
      screening would require surgical removal. CONCLUSION: Large numbers of patients
      are unaware of the existence of screening facilities for colorectal cancer, and
      are ignorant of the treatment of the disease. Increased public information is
      required to improve compliance with screening programmes, and to enable patients
      to take part in decisions about their management.

PMID- 9007431
TI  - Psychological aspects of gastrointestinal endoscopy: a review.

PMID- 9007432
TI  - A review of the technical and clinical aspects of virtual endoscopy.

PMID- 9007433
TI  - Endoscopic treatment of fistulas and abscesses in pancreatitis: three case
      reports.

PMID- 9007434
TI  - Biliary tract obstruction by unusual parasites.

PMID- 9007435
TI  - Sigmoid diverticular perforation relating to the migration of a polyethylene
      endoprosthesis.

PMID- 9007436
TI  - Endoscopic mucosectomy of the esophagus with a "shark-tooth" polypectomy snare.

PMID- 9007437
TI  - Endoscopic diagnosis of colonic tuberculosis: unusual presentation with two
      colonic strictures.

PMID- 9007438
TI  - Pancreatic-pleural fistula demonstrated by endoscopic retrograde
      cholangiopancreatography.

PMID- 9007439
TI  - Pin ingestion and upper endoscopy.

PMID- 9007440
TI  - Colonoscopic detection of cecal schistosomiasis mimicking a polyp in an
      asymptomatic individual.

PMID- 9007441
TI  - An endoscopic treatment for gastric angiodysplasia, using an endoscopic ligating
      device designed to treat esophageal varices.

PMID- 9007442
TI  - Laparoscopic retrieval of a needle migrated from the alimentary tract.

PMID- 9007444
TI  - Vanishing duodenal varix: unreported presentation causing massive bleeding.

PMID- 9007443
TI  - Olive pit pyloric obstruction.

PMID- 9007445
TI  - Endoscopic balloon sphincteroplasty: use in a patient with a Billroth II
      gastrectomy.

PMID- 9007446
TI  - Candida cholecystitis as an unusual complication of endoscopic retrograde
      cholangiography.

PMID- 9007447
TI  - Metastatic malignant melanoma of the papilla of Vater: an unusual case of
      obstructive cholestasis treated with biliary prostheses.

PMID- 9007448
TI  - Gastric ascariasis: a rare cause of upper gastrointestinal bleeding.

PMID- 9007449
TI  - Fibrolipoma of the colon with an unusual appearance.

PMID- 9007450
TI  - Electromyogram patterns during plantarflexions at various angular velocities and
      knee angles in human triceps surae muscles.
AB  - To investigate the influence of the various knee angles and ankle angular
      velocities on synergistic muscle activities, the surface electromyograms (EMG)
      were recorded from the triceps surae muscles, i.e. lateral gastrocnemius (LG),
      medial gastrocnemius (MG) and soleus (SOL) muscles. Six healthy young men
      performed ankle plantarflexions at three ankle angular velocities of 6, 30 and 60
      degrees.s-1 and three knee angles of 0, 30 and 60 degrees (0 degree equalling
      full extension) under constant load (5% and 10% maximal voluntary contraction).
      At the fully-extended knee angle (0 degree), peak values of integrated EMG (peak
      iEMG) during ankle plantarflexions were significantly increased (P < 0.05) in MG
      and in LG, but significantly decreased (P < 0.05) in SOL with increasing angular
      velocity. On the other hand, although the patterns of variation of the peak iEMG
      in each muscle at flexed knee angles (30 and 60 degrees) were very similar to the
      patterns seen at the fully-extended knee angle, there were no significant
      differences among angular velocities. During ankle plantarflexions at any of the
      angular velocities (6, 30 and 60 degrees.s-1) the peak iEMG were significantly
      increased (P < 0.05) in SOL, but were significantly decreased (P < 0.05) in MG
      following increases in the knee angles. These results would suggest the
      possibility of selective recruitment of motor units in humans depending on the
      angular velocity; however, this behaviour would appear to be weakened by fixing
      at flexed knee angles which cause an inhibitory influence on gastrocnemius
      muscles and a facilitative influence on SOL.

PMID- 9007451
TI  - Skeletal muscle buffering capacity and endurance performance after high-intensity
      interval training by well-trained cyclists.
AB  - Skeletal muscle buffering capacity (beta m), enzyme activities and exercise
      performance were measured before and after 4 weeks of high-intensity, submaximal
      interval training (HIT) undertaken by six well-trained competitive cyclists [mean
      maximal oxygen consumption (VO2max) = 66.2 ml.kg-1.min-1]. HIT replaced a portion
      of habitual endurance training and consisted of six sessions, each of six to
      eight repetitions of 5 min duration at 80% of peak sustained power output (PPO)
      separated by 1 min of recovery. beta m increased from 206.6 (17.9) to 240.4
      (34.1) mumol H+.g muscle dw-1.pH-1 after HIT (P = 0.05). PPO, time to fatigue at
      150% PPO (TF150) and 40-km cycle time trial performance (TT40) all significantly
      improved after HIT (P < 0.05). In contrast, there was no change in the activity
      of either phosphofructokinase or citrate synthase. In addition, beta m correlated
      significantly with TT40 performance before HIT (r = -0.82, P < 0.05) and the
      relationship between change in beta m and change in TT40 was close to
      significance (r = -0.74). beta m did not correlate with TF150. These results
      indicate that beta m may be an important determinant of relatively short-duration
      (< 60 min) endurance cycling activity and responds positively to just six
      sessions of high-intensity, submaximal interval training.

PMID- 9007452
TI  - Association between the anaerobic threshold and the break-point in the double
      product/work rate relationship.
AB  - A break point in the double product versus work rate relationship (DPBP) during
      incremental exercise has previously been reported. The aim of the current study
      was to investigate the frequency and degree of inter-observer agreement with
      which a DPBP could be detected. We also wished to determine its relationship, if
      any, to the lactic acidosis threshold (LATla). Ten normal volunteers performed
      continuous incremental bicycle ergometer exercise under three different
      concentrations of inspired oxygen (FiO2 = 0.21, 0.15 and 0.12). In addition, a
      group of patients with diseases expected to result in impaired exercise tolerance
      performed exercise under room air conditions. Gas exchange was measured
      continuously and double product was measured at 15-s intervals throughout
      exercise using an automated sphygmomanometer. Four observers, unaware of subject
      identity and test condition, analysed a total of 39 tests. All four observers
      detected a DPBP in 29 cases (74%) and an LAT in 35 cases (90%). The intra-class
      correlation coefficient was 0.76 for the DPBP and 0.93 for the LATla, indicating
      a reasonable level of agreement among observers for both break points. The DPBP
      was closely related to the LATla (r = 0.865, P < 0.0001), although it occurred at
      a slightly higher oxygen consumption (VO2, bias 0.137 1.min-1, 95% confidence
      intervals 0.041-0.233). We conclude that the DPBP is a common occurrence during
      incremental exercise. The close relationship between the DPBP and the LATla
      suggests that both may reflect similar events at the level of the skeletal muscle
      cell.

PMID- 9007453
TI  - Constant external work cycle exercise--the performance and metabolic effects of
      all-out and even-paced strategies.
AB  - The purpose of the present study was to establish whether the performance of an
      all-out sprint could be replicated and the metabolic responses moderated in two
      further trials involving pre-set constant average pedalling rates. A total of 24
      subjects (12 males and 12 females) completed a 30-s high-speed maximal all-out
      effort on a cycle ergometer against an applied resistance equal to 7.5% of their
      body mass. On two further occasions the applied resistance was increased so that
      the external work of the all-out effort could be replicated by adopting a pre
      determined constant average pedal rate. When the required pedal rate was within
      the range of 60-90 rev.min-1 the subjects were able to maintain the rate for the
      full 30-s and so could replicate the external work of the all-out effort. They
      were unable to sustain a faster constant rate within the range of 97-150 rev.min
      1 for the full 30 s, resulting in approximately 7% less external work being
      achieved (P < 0.05). A lower level of fatigue, reflected by less of a reduction
      in peak power output in a subsequent 6-s sprint (P < 0.05), arose as a result of
      similar work produced under constant paced conditions compared with the all-out
      effort. Also, post-exercise blood lactate, pH and ammonia were less disturbed (P
      < 0.05) following the paced trial compared with similar work produced in the all
      out effort. A possible explanation for these findings is that there may be a
      partial sparing of some type II fibres as a consequence of an initial submaximal
      intensity of exercise during the paced trial.

PMID- 9007454
TI  - General and local cold responses in humans after 2 weeks at high altitude.
AB  - To investigate the effects of a short-term high altitude residence (2 weeks
      between 4150 m and 6885 m in the Andes) on the general and local cold responses
      after descent, 11 subjects were submitted both to a whole body standard cold air
      test (SCAT, dry bulb temperature = 1 degree C, 2 h, nude, at rest) and to a local
      cold water test of the right upper limb (CWT, 5 degrees C, 5 min) both before and
      after the expedition. Compared to before the expedition, a lower systolic blood
      pressure was observed after the high altitude residence [130.00 (SEM 3.35) mm Hg
      vs 140.40 (SEM 4.74) mm Hg at the end of CWT, P < 0.05] whereas no significant
      change either in diastolic blood pressure or in heart rate was found. All skin
      temperatures of the right upper limb were lowered (P < 0.05). During SCAT, body
      temperatures were unchanged (rectal and mean skin temperature, Tsk) but metabolic
      heat production was slightly but significantly diminished [110 (SEM 4) W.m-2 vs
      125 (SEM 3) W.m-2, P < 0.05] and heat debt increased [11.37 (SEM 1.11) kJ.kg-1 vs
      9.30 (SEM 2.30) kJ.kg-1, P < 0.05]. Moreover, the time of onset of continuous
      shivering (d) was shortened [8.20 (SEM 1.90) min vs 17.30 (SEM 3.60) min, P <
      0.05] and the level of Tsk observed at (d) was higher [25.70 (SEM 0.80) degrees C
      vs 23.57 (SEM 0.78) degrees C, P < 0.05] suggesting an increase in the
      sensitivity of the thermoregulatory system despite the slight decreased shivering
      activity observed. It was concluded that general and local cold tolerance were
      modified by a short-term residence at altitude and that the changes observed were
      not in accordance with general or (and) local cold adaptation. In contrast, high
      altitude sojourn could be a risk factor for frostbite of the extremities.

PMID- 9007455
TI  - Thermoregulation during exercise in women who are taking oral contraceptives.
AB  - Thermoregulation during exercise was studied in seven women who were taking oral
      contraceptive pills for 3 weeks of each month. The subjects were studied once in
      the 3rd week of taking the pill (P) and once during the following week when they
      took no pil (N). Rectal temperature (Tre), heart rate (fc) and evaporative water
      loss (EWL, ventilated capsule technique) were measured while they walked on a
      treadmill for 60 min at 4.8 km.h-1 at a 10% gradient. Ambient temperature was 22
      degrees C. A venous blood sample was drawn 30 min before each experiment for
      measurement of hematocrit (packed cell volume, PCV), plasma osmolality (Osmpl),
      and plasma levels of the endogenous pyrogens interleukin-1 beta (IL-1 beta) and
      interleukin-6 (IL-6). Resting Tre was 0.31 degree C higher in P than in N (P <
      0.01) and Tre remained higher in P throughout the entire exercise period (P <
      0.01). Threshold Tre for the onset of EWL was 0.32 degree C higher in P than in N
      (P < 0.01). Exercise fc was 6.5 beats.min-1 higher in P than in N (P < 0.01).
      There was no significant difference in PCV, Osmpl, IL-1 beta or IL-6 between P
      and N. It was concluded that the administration of synthetic progestins in oral
      contraceptives causes an upward shift in the threshold for heat loss responses,
      resulting in higher body core temperatures both at rest and during exercise.
      There was no evidence that these alterations in thermoregulation were mediated by
      changes in body fluid balance or in plasma levels of IL-1 beta or IL-6.

PMID- 9007456
TI  - Respiratory variability in R-R interval during sinusoidal exercise.
AB  - The R-R interval varies with the cycles of respiration. The response of the
      variability in the R-R interval with respiration was examined during sinusoidal
      cycle exercise in 12 healthy young male subjects. Work rate varied sinusoidally
      between 30 W and 60% maximal oxygen uptake for an 8-min period. The higher the
      heart rate (HR), the smaller was the magnitude of the variation in R-R interval
      with respiration (delta RR). When HR increased with an increase in exercise
      intensity, however, delta RR tended to decrease more markedly at lower HR. On the
      other hand, since delta RR generally increased linearly during the decrease in HR
      with a reduction in exercise intensity, delta RR was greater during decreases in
      HR than during increases in HR at a similar HR. These results suggest that the
      contribution of the withdrawal of cardiac parasympathetic activity to increases
      in HR with increases in exercise intensity during sinusoidal exercise were
      greater at lower HR, and that the cardiac parasympathetic system was more
      activated during HR decreases than during HR increases at the same HR. From our
      findings it would seem that such complex parasympathetic HR regulaltion during
      sinusoidal exercise, which depends on the level of HR and the direction of the
      change in HR, may be influenced by factors other than the parasympathetic system,
      such as the cardiac sympathetic system.

PMID- 9007457
TI  - Some aspects of the acute phase response after a marathon race, and the effects
      of glutamine supplementation.
AB  - Strenuous exercise may be associated with immune suppression. However, the
      underlying mechanism is not known. A decrease in the plasma level of glutamine,
      which is utilised at a high rate by cells of the immune system, and an increase
      in the plasma level of some cytokines may impair immune functions such as
      lymphocyte proliferation after prolonged, exhaustive exercise. In two separate
      studies of the Brussels marathon, using similar protocols, the time course of the
      changes in the plasma concentrations of some amino acids (glutamine, glutamate,
      alanine, tryptophan and branched chain amino acids), acute phase proteins and
      cytokines (interleukins IL-1 alpha, IL-2, IL-6, tumour necrosis factor type a)
      was measured in male athletes. The numbers of circulating leucocytes and
      lymphocytes were also measured. Amino acid and cytokine concentrations have not
      previously been measured concomitantly in marathon runners; the measurement of
      some of these parameters the morning after the marathon (16 h) is novel. Another
      novel feature is the provision of glutamine versus placebo to marathon runners
      participating in the second study. In both studies the plasma concentrations of
      glutamine, alanine and branched chain amino acids were decreased immediately
      after and 1 h after the marathon. Plasma concentrations of all amino acids
      returned to pre-exercise levels by 16 h after exercise. The plasma concentration
      of the complement anaphylotoxin C5a increased to abnormal levels after the
      marathon, presumably due to tissue damage activating the complement system. There
      was also an increase in plasma C-reactive protein 16 h after the marathon. The
      plasma levels of IL-1 alpha were unaffected by the exercise, while that of IL-2
      was increased 16 h after exercise. Plasma IL-6 was increased markedly
      (approximately 45-fold) immediately after and at 1 h after exercise. Neopterine,
      a macrophage activation marker, was significantly increased post-exercise. There
      was a marked leucocytosis immediately after the marathon, which returned to
      normal 16 h later. At the same time there was a decrease in the number of T
      lymphocytes, which was further reduced within 1 h to below pre-exercise levels.
      Glutamine supplementation, as administered in the second study, did not appear to
      have an effect upon lymphocyte distribution.

PMID- 9007458
TI  - Lactate/H+ uptake by red blood cells during exercise alters their physical
      properties.
AB  - We investigated whether uptake of lactate anions by red blood cells (RBC) during
      maximal exercise altered certain cellular physical properties including volume,
      density and osmotic fragility. Irrespective of whether individuals undertook 1
      min of exercise at maximal effort or a progressive exercise test to exhaustion,
      whole-blood lactate concentration increased about tenfold relative to pre
      exercise values (P < 0.001). The plasma and cellular concentrations of lactate
      increased uniformly, which maintained a constant plasma-to-cell gradient.
      Exercise-induced increases in RBC osmotic fragility (P < 0.001) and mean cell
      volume (MCV; P < 0.05), and decreases in mean cell haemoglobin concentration
      (MCHC; P < 0.05) and cell density (P < 0.005) also occurred. These exercise
      induced cellular responses could be simulated in vitro by treating blood with L
      lactic acid (15 mM), but not by low pH (7.1) or L-lactate alone. The uptake of
      lactate by RBCs during vigorous exercise alters certain cellular properties.
      Although the physiological implications of these changes are unclear, the
      traditional view that the lactate anion has no known harmful effects should be
      reconsidered.

PMID- 9007459
TI  - Exercise and dietary cholesterol alter rat myocardial capillary ultrastructure.
AB  - The effects of a cholesterol-rich diet and exercise training on the myocardial
      capillary network and capillary ultrastructure were examined using Sprague-Dawley
      rats subjected to a 7-week exhaustive swimming scheme. A total of 16 animals were
      randomly divided into four groups consisting of normal dietinactive, normal
      dietexercise, cholesterol dietinactive, and cholesterol dietexercise. Following
      the experimental regimen the largest heart-mass-to-body-mass ratios were measured
      for the exercised rats fed a normal diet and the smallest ratios were found for
      the cholesterol-fed inactive rats. The capillary-to-fiber ratios and the
      capillary densities of the exercise-trained animals fed normal and cholesterol
      containing diets were higher than those of either of the inactive groups. Diet
      and exercise had significant and opposing effects on the number of capillary
      pinocytotic vesicles and no significant effect on vesicle size. The capillary
      endothelium of the exercise-trained animal groups occupied a smaller proportion
      of the capillary area when compared to diet-matched inactive groups. The results
      of this study imply that exercise training and a cholesterol-containing diet have
      opposite effects on the heart-mass-to-body-mass ratio and capillary pinocytotic
      vesicle number. Furthermore, exercise increases the capillary network of the
      myocardium and may facilitate receptor-mediated transport in heart capillaries.

PMID- 9007460
TI  - Blood oxygen saturation measured in the presence of a mixture of cyclopropane,
      sulfur hexafluoride, and ethane.
AB  - Some anesthetic gases interfere with the determination of blood O2 values. We
      evaluated, for its potential for such interference, a gas mixture containing
      (v/v) approximately 70% ethane, 20% sulfur hexafluoride, and 10% cyclopropane, as
      is currently used in trace amounts to determine ventilation-perfusion (v/Q)
      ratios. Normal human blood samples were first tonometered with control gas
      mixtures containing (v/v): (1) 20.9% O2, 0.04% CO2; (2) 16.0% O2, 4.0% CO2; and
      (3) 9.9% O2, 7.8% CO2. A large quantity (20.9%) of the v/Q mixture was blended
      experimentally into the control mixture and the tonometry repeated. The entire
      experiment was then repeated substituting pure N2 for the v/Q mixture as a
      dilution control. O2 values were determined by three methods: (1) a polarographic
      electrode, ABL-300 (ABL); (2) a spectrophotometric method, Co-Oximeter (COOX);
      and (3) a galvanic cell, Lex-O2-Con (LEX). The v/Q gas mixture lowered
      significantly all measured LEX values by 2.5-3.6 saturation percent (sat%), but
      showed no effect, dilution or otherwise, on the O2 values determined by the COOX
      and ABL methods. The N2 dilution lowered the LEX values by an average of only 0.9
      sat%; the ABL and the COOX were approximately 0.6 sat% lower. We therefore
      suggest that, if any of these O2 measurement methods are used in the presence of
      the v/Q mixture, baseline O2 values should be determined both before and after
      injection of the mixture into the bloodstream, prior to performing other
      experimental manipulations. The difference between the two values, if any, can
      then be used to interpret subsequent results.

PMID- 9007461
TI  - An accurate method of plasma volume measurement by direct analysis of Evans blue
      spectra in plasma without dye extraction: origins of albumin-space variations
      during maximal exercise.
AB  - The Evans blue dye (EBD) dilution method, including a dye extraction step, is a
      standard way of measuring plasma volume. This report describes a new direct
      spectrophotometric method, which is simple and specific and avoids the dye
      extraction step. To begin with, all the contaminants which may appear during a
      plasma volume study were added to plasma samples, prior to the absorbance
      measurements. In this way we calculated correction factors for the haemolysis and
      the turbidity of the plasma samples, without dye. The study of the visible
      spectra showed that the correction factors could be obtained by measuring
      absorbances at only four visible wavelengths: 780, 720, 619 and 578 nm. The
      addition of various amounts of contaminants to dye-containing plasma samples
      allowed us to obtain precise values for the absorbance errors. The previously
      defined correction factors were then applied, and the residual absorbance errors
      were found to become nil. This spectrophotometric method can be used to check the
      efficiency of a dye-extraction procedure, as well as to study other biological
      fluids containing EBD. When used to analyse a chronological series of blood
      samples this method appeared to provide an effective way of simultaneously
      studying the processes of plasma volume concentration and albumin extravasation
      induced by maximal exercise.

PMID- 9007462
TI  - The effect of environmental temperature on testosterone and cortisol responses to
      high intensity, intermittent exercise in humans.
AB  - The purpose of this study was to examine the testosterone, cortisol, and the
      molar ratio of testosterone to cortisol (T:C) blood concentration responses to
      intermittent, high intensity exercise in the heat. Eight active men [mean age 25
      (SD 3) years, mass 71.1 (SD 5.5) kg, height 175.9 (SD 4.4) cm] performed two
      series of five 15-s Wingate anaerobic power tests in both hot (H, 35 degrees C)
      and thermoneutral (TN, 22 degrees C) environments. Each period of exercise was
      separated by 30-s of active recovery. Each series was separated by 60 min of
      passive recovery. Blood samples were obtained before (PRE), immediately post
      (IP), and 5(5R), 10(10R), 15(15R), 30(30R), 45(45R), and 60(60R) min following
      exercise. Peak power was significantly higher, during the first series of
      exercise, in the H compared to TN. No significant differences were seen in any of
      the variables between the first and second series of exercise in either
      environmental condition. Furthermore, no significant differences between these
      conditions were observed in heart rate, blood lactic acid concentration, or
      rectal temperature. A significant decrease in cortisol concentration was observed
      between PRE and IP, during both conditions. However, no significant interactions
      between TN or H were seen. No change from PRE was observed in testosterone or T:C
      during either TN or H. It would appear that testosterone and cortisol respond
      similarly to repeated periods of short duration high intensity exercise, in
      either thermoneutral or moderately hot environments.

PMID- 9007463
TI  - Parental presence during induction of anesthesia: the surgeon's perspective.
AB  - Parental presence during induction of anesthesia (PPIA) remains controversial and
      little is known about surgeons' attitudes toward this clinical practice. A
      questionnaire was mailed to all the United States (US) members of the Surgical
      Section of the American Academy of Pediatrics and all members of the British
      Association of Paediatric Surgeons. Questions were asked about attitudes toward
      PPIA in the operating room and the prevalence of such practice. A total of 275
      subjects, constituting 72.4% of the compared groups, responded after three
      mailings. Sixty percent of the US respondents and 95% of the Great Britain (GB)
      respondents said they disagree with the statement "parents should never be
      present during induction of anesthesia". Ninety-two percent of the GB respondents
      and 69% of the US respondents thought PPIA decreases anxiety (p = 0.001) and
      increases the cooperation of the child (86% GB, versus 53% US, p = 0.001). Most
      US respondents (72%) reported that PPIA occurs in less than 25% of their cases,
      but most GB respondents (80%) reported PPIA in more than 75% of their cases (p =
      0.001). These differences in prevalence persisted after logistic-regression
      models were used to adjust for potential confounding demographic variables. We
      conclude that the attitudes and practice toward PPIA held by surgeons from the US
      and GB differ significantly. While a large percentage of the US sample agree that
      there are benefits in PPIA, only a minority report the routine use of PPIA in
      contrast to most respondents from GB who report PPIA as routine in their
      hospital.

PMID- 9007465
TI  - Pancreaticobiliary maljunction associated with nondilatation or minimal
      dilatation of the common bile duct in children: diagnosis and treatment.
AB  - It is known that the etiology of congenital biliary dilatation (CBD) is closely
      associated with pancreaticobiliary maljunction (PBMJ). Treatment of CBD today is
      primary excision of the cyst followed by hepaticoenterostomy. However, PBMJ
      without dilatation of the biliary tract has recently been reported and its
      treatment is still controversial. In adults, simple cholecystectomy without
      biliary reconstruction is often performed, because it usually presents as an
      anomaly of the gallbladder. Over 30 years, we have encountered 8 patients with
      PBMJ without dilatation of the common bile duct in 180 pediatric cases of CBD.
      The presenting symptoms of these patients were those of pancreatitis i.e.
      abdominal pain associated with elevation of serum amylase levels. Five cases
      presented with jaundice or a history of pale colored stools. Endoscopic
      retrograde cholangiopancreatography was performed to confirm the diagnosis. Five
      (62.5%) of these 8 patients were found to have dilatation of the common channel,
      which was seen in 50 (29%) of the 172 other cases with biliary tract dilatation.
      Three cases (37.5%) had proven protein plugs or debris at the level of the common
      channel, and this was observed in 28 (16%) of the 172 other cases. It is strongly
      suggested that the manifestation of clinical symptoms in these patients results
      from stasis or obstruction at the level of the common channel. In children who
      present with recurrent pancreatitis, PBMJ must be suspected even if the common
      bile duct appears to be normal. It is difficult to resolve these anomalies
      without operative repair. The authors consider that radical treatment of PBMJ is
      required in these children to prevent serious long-term complications.

PMID- 9007464
TI  - Esophageal ligation: effects on the development of fetal organic systems.
AB  - The role of amniotic fluid ingestion on the development of various fetal organic
      systems was evaluated in the rabbit model. The fetuses from 24 New Zealand white
      rabbits were studied on the 23rd day of gestation. Right ovarian-end fetuses
      underwent esophageal ligation (EL) or sham (SH) operations. Rabbits were
      submitted to hysterectomy on gestational day 30, and various organic systems of
      live fetuses were examined by weight and histological evaluations. Additionally,
      small intestinal enzymes were determined. Three fetal deaths, one in EL and two
      in SH groups, occurred with a total survival rate of 85%. EL resulted in
      increased amniotic fluid volume. Although fetal body weights (BW), lung, heart,
      liver and renal weights and liver weight/BW, lung weight/BW ratios did not
      differ, gastric, small intestinal and total gastrointestinal tract weights
      significantly decreased in EL group (p < 0.05). Additionally, gastric weight/BW,
      small intestinal weight/BW, total gastrointestinal tract weight/BW and renal
      weight/BW ratios were also significantly decreased (p < 0.01). Sucrase and
      maltase activities were not detectable in either group. Lactase activity in
      proximal small intestinal tissue was significantly decreased in EL group (p <
      0.05). Mid and distal small intestinal tissue lactase activities did not reveal
      any significant difference among groups. Histologically, alveolar enlargement and
      alveolar thickening in fetal lungs, decreased glomerular count and tubular
      degeneration in fetal kidneys, and slight changes in fetal livers such as
      cellular vacuolization and reduction in central vein count were observed in the
      fetuses with esophageal ligation. While small intestinal tissues showed no marked
      changes, fetal stomach tissues in EL group revealed marked histological
      alterations consistent with erosive gastritis. This study suggests that amniotic
      fluid ingestion has no important effects on fetal somatic growth but effects the
      development of various fetal organic systems. Since the nutritional role of
      amniotic fluid is obscure, changes in amniotic fluid dynamics, and/or impairment
      of release of some possible fetal organotrophic factors, and/or unused states of
      the organs may be responsible for the morphologic changes secondary to esophageal
      ligation.

PMID- 9007466
TI  - Hepatic veno-occlusive disease in Wilms' tumor.
AB  - Invasive surgical procedures will be avoided by recognition of veno-occlusive
      disease (VOD) as a clinical syndrome which sometimes leads to serious
      complications in children receiving Actinomycin D for Wilms' tumor. In order to
      document the unusually frequent occurrence of VOD far beyond the observations of
      others, a prospective study was undertaken in 13 consecutive Actinomycin D
      treated children. There were 9 children experiencing 27 events of mostly mild
      VOD. Six of them were below 3 years of age having in 5 cases a unilateral kidney
      tumor on the right side. The criteria used for VOD were painful hepatomegaly and
      abdominal distension accompanied by weight gain, ascites, hemoglobin and platelet
      drop, with or without elevated bilirubin level found in all patients developing
      VOD. Supportive management of these patients should attempt to preserve
      respiratory and renal function, generally resulting in a favorable outcome.

PMID- 9007467
TI  - Spontaneous perforation of the biliary tract in infancy: a series of 11 cases.
AB  - Eleven patients presenting with spontaneous perforation of the biliary tract were
      treated at Bicetre Hospital between 1971 and 1993. Three groups were
      individualised, each with a different pattern of local presentation: generalised
      biliary peritonitis (n = 2), localised biliary peritonitis (n = 4), secondary
      biliary stenosis (n = 5). In each case, cholestatic jaundice developed after a
      postnatal symptom-free interval. Ten patients were operated on. Perforation was
      located in the cystic duct (n = 2), at the junction of the cystic and hepatic
      ducts (n = 4), in the common hepatic duct (n = 1) or common bile duct (n = 1).
      The site of perforation was no longer identifiable in two cases with stenosis. A
      cholecystectomy was performed in the 2 cases with cystic duct perforation; in the
      cases of lesions of the main duct, either simple external biliary drainage (n =
      3) or biliary reconstruction (n = 5) was carried out. Postoperative complications
      included bile leak (n = 2), ascending cholangitis (n = 1), portal vein thrombosis
      (n = 2). Five patients were submitted to further surgery including biliary
      revision (n = 3), porto-systemic shunt (n = 1), and other procedures (n = 2). One
      infant died from postoperative sepsis; 2 were lost to follow-up, one of which
      probably did not survive; 4 are alive and well. Late sequelae are present in 4
      children: portal hypertension (n = 1), mild residual bile duct dilatation without
      cholestasis (n = 1), and mild to moderate liver fibrosis (n = 2). Prompt
      diagnosis and appropriate treatment should improve the prognosis of this rare
      condition.

PMID- 9007468
TI  - Hepatic trauma in children: long-term follow-up.
AB  - The purpose of this report is to assess the role of long-term clinical and
      hepatic ultrasound (US) follow-up in children who sustained blunt liver trauma.
      Forty-three children with blunt hepatic injury were prospectively studied between
      1976 and 1994 in our institution. Four patients died (9%). Fourteen children
      (52%) were operated upon and 13 (48%) were treated conservatively. Twenty-seven
      patients were recalled for a long-term echography (US) with a mean time span of 6
      years after trauma. The physical examination and the liver tests were normal in
      all patients. The US aspect of the liver was abnormal in 22% of our cases,
      showing hypoechogenic areas and anomalies of the biliary tract in four patients
      (11%). Cholelithiasis secondary to hemobilia was demonstrated in 2 patients.
      Cholecystectomy was performed in one patient because of posttraumatic strictures
      of the biliary tract. All patients with US anomalies of the liver and biliary
      tract were clinically asymptomatic and had normal liver tests. We recommend a
      follow-up US in children having sustained blunt hepatic injury about 6 months
      after the trauma. If no cholelithiasis or alteration of the biliary tract is
      present, no other follow-up procedure seems necessary.

PMID- 9007469
TI  - Appendicitis after blunt abdominal trauma: cause or coincidence?
AB  - The association of appendicitis and blunt abdominal trauma (BAT) is an
      exceptionally rare occurrence with a few case reports in the literature. The main
      question whether this association is a result of causative or coincidental
      relationship has not been evaluated among children. A retrospective clinical
      study was performed to clarify the pathogenesis, incidence, clinical
      characteristics and outcome of appendicitis diagnosed in children during the
      hospitalization period following blunt abdominal trauma (BAT). The records of 554
      patients with BAT who were admitted to our unit between 1979 and 1993 inclusive
      were reviewed. Five patients (0.90%), 3 males and 2 females, with a mean age of
      9.4 +/- 1.4 were found to have appendicitis. None of these patients had any signs
      or symptoms related to appendicitis prior to BAT. Bruising and rupture of the
      mesoappendix were noted in 3 patients while edema and hematoma of appendix and
      terminal ileum were found in two. Full recovery was achieved in all patients
      following appendicectomy. Our incidence of 0.90% is statistically significantly
      higher than the highest incidence rate of appendicitis stated in the literature
      during childhood (t-test for population proportion, t = 2.892; p < 0.05). We
      emphasise the possibility of a causative relationship between appendicitis and
      BAT depending on the clinical characteristics, operative findings, statistically
      significant high incidence rate and literature review.

PMID- 9007471
TI  - Management of uncommon complications of definitive operations of Hirschsprung's
      disease.
AB  - In Hacettepe University Children's Hospital, 229 Hirschsprung patients who had
      undergone definitive operations of Hirschsprung's disease (HD) between 1976-1993
      were evaluated for the occurrence of uncommon complications. Two hundred and
      thirteen of these patients were operated on in our hospital and 16 of them
      referred to us after definitive operation. The most uncommon complication in the
      presented series was the fistula; namely rectourinary, rectovaginal, ileorectal
      and perianal. One patient acquired rectourethral fistula after Swenson operation.
      He had undergone redo Swenson operation after an unsuccessful attempt of fistula
      repair. In our series we detected two patients with ileorectal fistula one of
      them has also a perianal fistula. These two patients were presented with
      intractable enterocolitis that caused a delay in treatment. Both of them had
      undergone ileorectal fistula repair with success. We encountered two rectovaginal
      fistulae among patients who were referred to us after definitive operations. Both
      of them were managed with redo operation. One patient was referred to us after
      Swenson operation with perianal fistula and had undergone fistulotomy. The
      management of rectourinary and rectovaginal fistulae other than redo operation
      was proved to be unsuccessful.

PMID- 9007470
TI  - Neonatal intestinal obstruction: reducing short-term complications by surgical
      refinements.
AB  - Over the last ten years advances in neonatal intensive care, such as the advent
      of parenteral nutrition, have led to a significant decrease in the mortality
      rates of neonates with intestinal obstruction. Nevertheless, surgical short-term
      complications associated with the intestinal anastomosis performed, such as
      stenosis or leakage, and long-term nutritional complications due to extensive
      resections are still responsible for mortality and for a high morbidity rate. 39
      newborns referred to our hospital in the past 3 years for intestinal obstruction
      were retrospectively evaluated with particular attention to the surgical
      management, surgical techniques and subsequent complications. Age on admission
      was from 1 hour to 24 days; weight from 1.4 to 3.8 kg; 41% of newborns had a
      prenatal diagnosis. 57 surgical procedures were performed: among them 44
      intestinal anastomoses. Short-term surgical complications, namely perforation and
      stenosis, were observed in 18.1% of anastomoses. The complication rate after
      simple end-to-end anastomosis was as high as 30%. However, certain technical
      refinements such as tailoring the dilated upper pouch, positioning a
      transanastomotic feeding tube and an intubated lateral stoma resulted in a much
      lower complication rate (3.7%). Thus, in our experience these technical
      refinements are effective in reducing the incidence of short-term surgical
      complications.

PMID- 9007472
TI  - Salvage of Soave-Boley endorectal pull-through by conversion to a classical Soave
      procedure.
AB  - The endorectal pull-through procedure described by Soave and subsequently
      modified by Boley to include primary coloanal anastomosis is one of the most
      commonly performed procedures for Hirschsprung's disease. The Boley modification
      carries a 5-10% risk of dehiscence of the colo-anal anastomosis. This is
      generally treated with proximal colonic diversion and delayed revision of the
      pull-through. We report the use of the original Soave procedure to treat this
      complication.

PMID- 9007474
TI  - Obstructive jaundice caused by lymph node compression in a child.

PMID- 9007473
TI  - Gastric outlet obstruction due to starch granuloma and peritonitis.
AB  - Starch peritonitis (SP), is a relatively rare surgical complication. This
      together with a puzzling acute clinical pattern, makes diagnosis more difficult.
      We describe a child who developed a full blown SP, mimicking gastric outlet
      obstruction, 3 weeks after an antireflux procedure. We would like to stress the
      importance of making the correct preoperative diagnosis, in order to spare the
      patient an unnecessary operation. This may be difficult.

PMID- 9007475
TI  - Pancreatoblastoma in children. Case report and review of the literature.
AB  - Pancreatolblastomas are rare embryonal malignancies in childhood. We report a 3
      year-old girl with a tumor of the head of pancreas. Staging by bone scintigraphy
      and CT scans of abdomen and chest did not show evidence of metastatic disease.
      Tumor markers showed elevated levels of alpha-1 fetoprotein (64 ng/ml; normal 0
      10 ng/ml) and lactate dehydrogenase (423 U/l; normal range below 300 U/l). The
      tumor was macroscopically completely removed by local resection. Postoperative
      tumor grading was pT1, NO, MO. The child recovered very soon after surgery
      without severe complications. Tumor markers dropped to normal values, indicating
      complete remission (follow-up time 12 months). According to the biological growth
      characteristics of pancreatoblastomas and to the literature, localized and non
      metastatic tumors should be completely resected without radical
      pancreatoduodenectomy and without adjuvant chemotherapy. This is the most
      conservative therapy with a good prognosis. However, metastatic disease,
      primarily inoperable conditions or local relapses are indications for
      chemotherapy combined with radiotherapy and followed by resection of the tumor.
      At present, the prognosis of such cases is rather poor.

PMID- 9007476
TI  - Segmental cecal dilatation with absent appendix: a case of failure of appendiceal
      regression?
AB  - A rare intestinal malformation is reported in a boy 11 years old with a 3-year
      history of abdominal pain and chronic anemia. Laparotomy revealed a large cecal
      mass extending beyond the ileocecal valve in the place of the appendix, with
      bleeding mucosal ulcers.

PMID- 9007477
TI  - Volvulus of the sigmoid colon as a complication of segmental dilatation of the
      colon. Report of 2 cases.
AB  - Sigmoid volvulus is an unusual cause of intestinal obstruction in children. We
      report two cases of sigmoid volvulus as a complication of segmental dilatation of
      the colon occurring in two girls (5 years old and 9 years old) previously treated
      for chronic constipation. In both cases the constipation had been recognised
      since the neonatal period mimicking a Hirschsprung's disease, a diagnosis which
      has been excluded after rectal biopsy. The delayed diagnosis of segmental
      dilatation of the sigmoid colon followed the volvulus. Segmental colonic
      resection resulted in both cases in the cure of the constipation.

PMID- 9007478
TI  - Neonatal bladder rupture: an unusual complication of umbilical catheterization.
AB  - Bladder injury in the neonatal period is an exceedingly rare phenomenon that is
      usually iatrogenic. Bladder rupture as a complication of umbilical
      catheterization in a newborn with urinary ascites, respiratory distress and
      hematuria is presented and discussed.

PMID- 9007479
TI  - Our modification of duodeno-jejuno-anastomosis; comment upon article duodenal
      atresia: a comparison of three modes of treatment.

PMID- 9007480
TI  - Neonatal diabetes and intra-uterine growth retardation.

PMID- 9007481
TI  - Dilated cardiomyopathy and thrombo-embolism.
AB  - The purpose of this study was to investigate the incidence, outcome and
      prevention of thrombo-embolism in children with dilated cardiomyopathy. From 130
      patients with dilated cardiomyopathy, 17 (14%) showed evidence of thrombo
      embolism. Seven had initial cardiac thrombus, 7 exhibited initial embolus and in
      3 thrombo-embolism was only diagnosed at autopsy. All 17 patients showed
      seriously impaired systolic function of the left ventricle with fractional
      shortening (FS) of 10 +/- 3%, range 5%-17%, as compared to those without thrombo
      embolism with FS of 17% +/- 6%, range 5%-26% (P < 0.0001). Seven patients were
      treated with oral anticoagulants once thrombo-embolism had been diagnosed; one of
      them experienced a further embolic event as opposed to three out of four patients
      not treated with anticoagulants. CONCLUSION: All children with dilated
      cardiomyopathy and fractional shortening below 20% should be treated with
      prophylactic anticoagulative agents.

PMID- 9007483
TI  - Early mortality in childhood diabetes in Austria--a population based cohort
      study.
AB  - All Austrian patients with insulin dependent diabetes diagnosed between 1979 and
      1990 and age at onset below 15 years were followed from manifestation until death
      or until 31 December 1990 by cross linking the diabetes registry data with the
      National Mortality database (death certificates). Out of the cohort consisting of
      1185 cases, 6 had died during the study period, resulting in a standardized
      mortality ratio of 1.53 for the total cohort. Of the patients 50% died due to
      acute diabetic complications including 2 children at onset of the disease. The
      risk for premature death in this cohort of very young insulin dependent diabetes
      mellitus patients was only slightly increased. In comparison to previous studies
      it is rather low, but comparable to recent investigations in northern Europe.
      CONCLUSION: Although the mortality of diabetic children and adolescents in
      Austria is only marginally higher than in nondiabetics, there are still deaths
      which should be preventable in this age group.

PMID- 9007482
TI  - Functional assessment and clinical classification of androgen sensitivity in
      patients with mutations of the androgen receptor gene. German Collaborative
      Intersex Study Group.
AB  - In the genetic male, mutations of the androgen receptor (AR) gene cause
      phenotypes ranging from female to subfertile male. Binding assays on genital skin
      fibroblasts and DNA analysis alone provide incomplete information about receptor
      function. We used the sex hormone-binding globulin (SHBG) response to stanozolol
      as a measure of AR function and correlated the results with phenotypes which were
      classified according to the degree of defective masculinization. Of the 34
      patients investigated, 9 had complete, and 14 had partial androgen insensitivity
      syndrome (AIS) with predominantly female, ambiguous, or predominantly male
      phenotype. Eleven subjects served as controls. Mutations were characterized using
      polymerase chain reaction-single strand conformation polymorphism analysis and
      direct DNA sequencing. DNA analysis revealed two major deletions, two minor
      defects leading to premature stop codons in exon 1, and 19 point mutations in the
      DNA- and hormone-binding domains of the AR gene. After stanozolol, SHBG remained
      unchanged in patients with complete AIS (102.0 +/- 3.8 [SE]%; range 92.4%-129% of
      the initial value). The SHBG decrease was diminished in partial AIS with
      predominantly female (83.8% +/- 1.7%; range 81.3%-87.0%), ambiguous (80.4% +/-
      4.4%, range 68.4%-89.1%), and predominantly male (mean 65.9% +/- 4.9%, range
      48.6%-80.8%) phenotypes, and normal in controls (51.4% +/- 2.1%, range 35.6%
      62.1%). Differences between controls and each AIS group were statistically
      significant (P < 0.05 - < 0.0001). A close correlation was found between the
      degree of undermasculinization (AIS phenotype) and the SHBG response.
      CONCLUSIONS: The SHBG test provides functional information about the severity of
      the receptor defect in vivo and hence adds to the structural information provided
      by DNA analysis. It detects receptor defects due to mutations within the entire
      gene, including the DNA-binding domain, and is a rapid, simple, and cost
      effective procedure. It may provide useful information for the diagnosis and
      management of affected children.

PMID- 9007484
TI  - Evidence for induction of polysaccharide specific B-cell-memory in the 1st year
      of life: plain Haemophilus influenzae type b-PRP (Hib) boosters children primed
      with a tetanus-conjugate Hib-DTPa-HBV combined vaccine.
AB  - The lack of an adequate immune response to the major polysaccharide of the
      Haemophilus influenzae type b (Hib) capsule (polyribosyl ribitol phosphate) (PRP)
      in very young infants (< 18 months) can be overcome by conjugating PRP to a T
      cell dependent carrier protein. We studied whether administration of a tetanus
      PRP conjugate vaccine reconstituted with a diphtheria-tetanus-acellular pertussis
      hepatitis B (DTPa-HBV) vaccine as a three dose primary course at 3, 4 and 5
      months of age induced PRP-specific immunological memory, by examining the anti
      PRP response to a dose of unconjugated PRP given with the DTPa-HBV booster
      approximately 1 year later. The unconjugated PRP elicited protective anti-PRP
      antibody levels (> or = 0.15 microgram/ml) in all but 3 of the 369 vaccinees,
      including 13 infants who failed to demonstrate a measurable immune response after
      the primary course. In a sub-cohort of 54 subjects all had anti-PRP levels > or =
      0.5 microgram/ml within 7-14 days of the booster showing a rapid anamnestic type
      response. Both primary and booster responses were predominantly IgGl indicating a
      T-cell dependent response. The DTPa-HBV components elicited protective anti
      diphtheria, anti-tetanus and anti-HBs antibody levels in > or = 98.5% of
      vaccinees, and immune responses to each of the acellular pertussis vaccine
      components in 92.3%-97.3% of subjects. CONCLUSION: The tetanus-PRP conjugate
      vaccine not only elicited a good primary humoral response, but also induced
      immunological memory so that the infants were able to mount a large and rapid
      immune response to subsequent exposure to plain PRP, indicating that protection
      against circulating wild-type Hib had been generated. Successful induction of
      immunological memory occurred even when there was no measurable humoral anti-PRP
      response to the primary course. Tetanus-PRP conjugate vaccine can be used in
      combination with DTPa-HBV vaccine, when administered separately or as a single
      injection in the same syringe, in primary immunisation schedules at 3, 4 and 5
      months of age.

PMID- 9007485
TI  - Cytokines in acute rheumatic fever.
AB  - Plasma concentrations of inflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL
      8 and TNF alpha) were determined by ELISA in 27 patients with acute rheumatic
      fever (RF), 12 with only arthritis (RFA) and 15 with rheumatic heart disease
      (RHD), before, during and after treatment. Altogether, significant increases in
      TNF alpha, IL-8 and IL-6 levels were observed in the acute phase as compared to
      the data found during and after treatment. No significant differences were
      observed for the other cytokines. Elevations of one or more of the inflammatory
      cytokines were observed in 9 of 12 patients with RFA, and 12 of 15 with RHD.
      Increase of TNF alpha (6/9) and IL-8 (5/9) levels were higher in RHD patients
      with cardiac failure. These cytokines were below the detection limits on day 7 of
      treatment in all 22 patients, except in two, and in all 10 days after treatment.
      CONCLUSIONS: These findings suggest that inflammatory cytokines, as TNF alpha, IL
      8 and IL-6, may play a pathogenic role in rheumatic fever.

PMID- 9007486
TI  - Tendency toward atopy in Kawasaki disease.
AB  - To evaluate the possible trend towards developing allergic disease in children
      who had suffered from Kawasaki disease (KD), we evaluated data related to allergy
      that were collected by parental questionnaire on 1,165 children who had suffered
      from KD. Comparisons were made with 5,825 sex- and age-matched control children.
      The incidence of household pets and of cigarette smoking in the family were
      significantly lower in the children with a history of KD than in those of control
      children. A family history of allergy was significantly more common in the
      children with a history of KD (71%) versus the controls (56%) (P < 0.001). The
      incidence of atopic dermatitis and of allergic rhinitis was significantly higher
      (by approximately 1.7 times) in the KD children versus the control group (P <
      0.01), even in subgroups with no family history of allergy. CONCLUSION: We
      suggest that a genetic predisposition to atopy may be associated with a
      susceptibility to KD. Patients with KD tended to develop atopic dermatitis and
      allergic rhinitis.

PMID- 9007487
TI  - Spinal osteomyelitis caused by Proteus mirabilis in a child.
AB  - Osteomyelitis due to Proteus mirabilis is rare. Spinal osteomyelitis caused by
      this organism has only been described in adults. This is the first paediatric
      case of P. mirabilis vertebral osteomyelitis.

PMID- 9007488
TI  - Association of hiatal hernia with mitral valve prolapse.
AB  - Cardiological investigation of 23 children (13 boys) with sliding hiatal hernia
      revealed mitral valve prolapse in 18 patients (10 boys) suggesting a very high
      association rate of 78.2%. No other signs of connective tissue weakness were
      seen. CONCLUSION: Cardiological evaluation is recommended in every child with
      hiatal hernia.

PMID- 9007489
TI  - Congenital microgastria, growth hormone deficiency and diabetes insipidus.
AB  - Microgastria is a rare malformation of the stomach always associated with
      variable patterns of malformations of the lung, heart, aortic arch, skeleton, and
      central nervous system. Many cases present with asplenia and hepatic symmetry as
      well as intestinal malrotation. We report a first case of a 4.5-year-old girl
      with congenital microgastria in association with growth hormone deficiency,
      diabetes insipidus, brachyoesophagus, hernia of the diaphragm, gastro-oesophageal
      reflux, intestinal malrotation, enlarged symmetrical liver, asplenia, as well as
      mental and statomotor retardation. CONCLUSION: Congenital microgastria is always
      associated with malformations of other organs. Patients at any age presenting one
      of the symptoms: failure to thrive, vomiting, asplenia, midline defects and parts
      of the VACTERL association should be carefully examined to exclude microgastria.

PMID- 9007490
TI  - Effect of dexamethasone therapy on cerebral and ocular blood flow velocity in
      premature infants studied by colour Doppler flow imaging.
AB  - Although dexamethasone (DEX) is used widely in neonates with chronic, and even
      recently with acute respiratory disease, its potential side-effects on human
      cerebral and ocular haemodynamics remain unknown. The effects of DEX on cerebral
      and ocular blood flow velocities were assessed in preterm infants with lung
      disease and mechanical ventilation. Ten ventilated preterm infants received DEX
      (0.25 mg/kg/12 h) for ongoing chronic lung disease or extubation failure. Colour
      Doppler flow imaging studies of the internal carotid, anterior cerebral and
      ophthalmic arteries were made before and 10, 30, 60, 120 and 240 min after the
      1st, 3rd, and 5th doses of DEX. Peak systolic, temporal mean, and end-diastolic
      flow velocities and the resistance index (RI) of Pourcelot were determined. The
      brain was examined by ultrasonography before and at the end of each Doppler
      study. All patients were continuously monitored for transcutaneous blood gases
      and blood pressure. All flow velocities and the RI of the internal carotid,
      anterior cerebral and ophthalmic arteries showed a similar trend throughout the
      study. The means of the values averaged for the 240 min of cerebral and ocular
      blood flow velocity with each dose were progressively higher and the values of
      the RI progressively lower up to the 5th dose. The most significant changes
      occurred in end-diastolic flow velocity and consisted of a percentage increase
      between the 1st and 5th dose of 72% in the internal carotid artery, 102% in the
      anterior cerebral artery and 84% in the ophthalmic artery. Changes in arterial
      blood pressure followed a pattern similar to that of changes in blood flow
      velocity. CONCLUSIONS: Dexamethasone increments cerebral and ocular blood flow
      velocity. We speculate that this finding may be relevant to the development of
      brain and retinal injury.

PMID- 9007491
TI  - Blood transfusion and chronic lung disease in preterm infants.
AB  - Frequent blood transfusions may produce changes in iron status which can give
      rise to oxygen-derived free-radical (ODFR) generation and oxidative injury.
      Preterm infants developing chronic lung disease (CLD) receive significantly more
      transfusions. A total of 73 very preterm infants had weekly estimations of serum
      iron, transferrin, transferrin saturation, ferritin, caeruloplasmin, bleomycin
      detectable ('free') iron (BDI), and thiobarbituric acid reacting substances
      (TBARS) made over the first 28 days. Thirty infants remained oxygen dependent at
      36 weeks postmenstrual age and were termed as having CLD. They were significantly
      lighter and less mature at birth and received more than twice as many
      transfusions during the 1st month. They had significantly lower transferrin
      levels initially but similar total iron and transferrin saturations as non-CLD
      infants. Ferritin and caeruloplasmin levels rose to significantly higher levels
      over the 1st month in CLD infants, and ferritin levels were significantly related
      to the number of transfusions given. Infants with higher ferritin levels were
      more likely to show BDI, although this was not associated with increased lipid
      peroxidation as evidenced by higher TBARS. CONCLUSION: It is unlikely that
      oxidative injury from ODFRs induced by blood transfusion contributes to the risk
      of developing CLD in preterm infants.

PMID- 9007492
TI  - Inhaled versus systemic steroids in chronic oxygen dependency of preterm infants.
AB  - The speed of action and side-effects of systemic verus inhaled steroids was
      compared in infants with mild-moderate oxygen dependency. Forty infants (median
      gestational age 27 weeks) were randomized to receive either 10 days of
      dexamethasone (systemic group) or budesonide (100 micrograms qds) (inhaled
      group). At randomization, there was no significant difference in the gestational
      or postnatal age, inspired oxygen requirements or compliance of the respiratory
      system of the two groups. After 36 h of treatment, there were significant changes
      (P < 0.01) in both the inspired oxygen concentration and compliance of the
      respiratory system in the systemic but not the inhaled group. Only after 1 week
      of inhaled therapy were improvements in respiratory status noted but, even at
      that time, the inspired oxygen requirement was significantly lower in the
      systemic versus the inhaled group. In the systemic group only, however, were
      there significant increases in blood pressure. CONCLUSION: Systemically
      administered rather than inhaled steroids appear to have a faster onset of
      action.

PMID- 9007493
TI  - Effect of low and moderate doses of recombinant human erythropoietin on the
      haematological response in premature infants on a high protein and iron intake.
AB  - There is no consensus regarding protein intake and the doses of recombinant human
      erythropoietin (r-HuEpo) and iron in the treatment of anaemia of prematurity
      (AOP). This open, randomized study has compared the effectiveness of 50 IU r
      HuEpo/kg with that of 100 IU/kg, both given subcutaneously thrice weekly. In
      addition, two different protein supplements have been compared; lyophilized human
      milk protein and a commercial cow's milk product. Total protein intake was 3 g/kg
      per day. Daily iron dose was 18-36 mg. "Healthy" preterm infants (n = 32, birth
      weight: 800-1400 g, gestational age < or = 31 weeks) were studied from age 3 to 8
      weeks. The two protein regimens yielded no differences in body growth,
      reticulocyte count or Hb concentration. In both r-HuEpo dose groups increased
      number of reticulocytes followed start of treatment; higher levels were, however,
      found in the group receiving 100 IU/kg. Mean Hb concentration plateaued at 12
      g/dl for infants receiving 100 IU/kg, at 11 g/dl in the 50 IU/kg group. Even
      though serum levels of ferritin and transferrin saturation indicated no iron
      deficiency, soluble transferrin receptor increased in both groups, more rapidly
      and to higher levels in the 100 IU/kg group. In addition, the number of infants
      having more than 8% hypochromic red cells increased in both groups. CONCLUSIONS:
      Commercial cow's milk protein added to human milk was as good as human milk
      protein supplementation in supporting growth and erythropoiesis. Fifty IU/kg r
      HuEpo thrice weekly during AOP stimulated erythropoiesis significantly, but less
      so than 100 IU/kg. Even when using high oral doses of iron to preterms receiving
      r-HuEpo, our data suggested a certain degree of iron deficient erythropoiesis.

PMID- 9007494
TI  - Hydrops fetalis and fibrosarcoma: case report of an uncommon association.
AB  - Fetal hydrops associated with neonatal tumours is an uncommon occurrence. The
      diagnosis can be established prenatally by ultrasound examination. The treatment
      of choice is surgery which may be curative. We report the case of a male born at
      32 weeks gestation who presented with severe hydrops fetalis and a thoracic mass.
      The child could not be operated upon because of rapid clinical deterioration. The
      autopsy findings confirmed the diagnosis of congenital fibrosarcoma. This is, to
      our knowledge, the first case of hydrops fetalis associated with fibrosarcoma.
      CONCLUSION: The association of hydrops fetalis and fibrosarcoma is an exceptional
      observation but can be added to the long list of differential diagnoses of non
      immune hydrops.

PMID- 9007495
TI  - Respiratory control in children with Prader-Willi syndrome.
AB  - Physiological parameters of infants and children with Prader-Willi syndrome were
      examined in order to clarify whether there were indicators of disturbed
      respiratory control mechanisms in the pre-obesity stage of the syndrome. From
      January 1993 to March 1995 in eight patients with Prader-Willi syndrome (five
      boys, three girls, aged 6 weeks-12.5 years), polysomnography was performed and
      compared with 28 children matched for gestational age, sex, birth weight and age
      at sleep study. The recordings included thoracic and abdominal breathing
      movements, nasal airflow, tcPO2, tcPCO2, oxygen saturation, EEG, EOG and ECG.
      Respiratory responses to hypercapnia during quiet sleep were obtained from five
      Prader-Willi patients and ten peers. The Prader-Willi group showed an increased
      number of apnoeas per hour of sleep, a decreased nadir of oxygen saturation,
      increased maximum of the instantaneous heart rate and decreased respiratory
      responses to hypercapnia during quiet sleep. CONCLUSION: These findings indicate
      a primary disturbance of central respiratory control in patients with Prader
      Willi syndrome which may be worsened by the development of obesity.

PMID- 9007496
TI  - Empty sella, growth hormone deficiency and pseudotumour cerebri: effect of
      initiation, withdrawal and resumption of growth hormone therapy.
AB  - An 11-year-old boy with normal visus and eye fundus, but with empty sella, growth
      hormone (GH) deficiency and central diabetes insipidus was found to have
      intracranial hypertension with papilloedema after 6 months of catch-up growth
      under recombinant human GH (rhGH) replacement therapy. Withdrawal of rhGH therapy
      was associated with normalisation of intracranial pressure within 1 week. Three
      months later, resumption of rhGH therapy at a lower dose was again followed by
      pronounced growth acceleration, but now without papilloedema. CONCLUSION:
      Children with empty sella and GH deficiency may be prone to rhGH-induced
      pseudotumour cerebri which appears to be rapidly reversible and dose-dependent.

PMID- 9007497
TI  - Plasma carotenoids in German children and adolescents.
AB  - Carotenoids are important antioxidants and precursors of vitamin A, but only few
      studies have been carried out on plasma carotenoid levels in paediatric age
      groups. Using high-performance liquid chromatography we analysed concentrations
      of four important carotenoids (alpha-carotene, beta-carotene, cryptoxanthin,
      lycopene) in 129 healthy German children and adolescents (81 boys, 48 girls; age
      1-18 years). For all carotenoids analysed, no significant differences between
      girls and boys were found. alpha-Carotene values ranged from 0 mumol/l (below
      detection limits) to 0.73 mumol/l (0-395 micrograms/l), beta-carotene from 0.09
      mumol/l to 2.68 mumol/l (48-1443 micrograms/l), lycopene from 0 mumol/l to 1.51
      mumol/l (0-815 micrograms/l), and cryptoxanthin from 0 mumol/l to 0.30 mumol/l (0
      164 micrograms/l), respectively. Data analyses according to age groups showed a
      tendency towards higher levels of alpha- and beta-carotene, and lower levels of
      lycopene in young children. These differences were significant when children
      younger than 4 years were compared with those above 8 and 12 years, respectively.
      The data presented may serve as reference values for studies on children with
      nutritional disorders and diseases associated with a risk of vitamin
      deficiencies. CONCLUSION: Carotenoids are important antioxidants and singlet
      oxygen scavengers. Plasma levels of alpha-carotene, beta-carotene, lycopene and
      cryptoxanthin were determined in 129 healthy German children and adolescents.
      Highest values were found for beta-carotene and lycopene.

PMID- 9007498
TI  - Cases of the month: three children with abdominal complaints.

PMID- 9007499
TI  - Arthrogryposis, renal tubular dysfunction, cholestasis, ichthyosis syndrome
      (ARCI)

PMID- 9007500
TI  - Pelvic ultrasonography in sexual precocity.

PMID- 9007501
TI  - Inhibitory effect of dopamine treatment on Na+/K(+)-ATPase activity in preterm
      infants.

PMID- 9007502
TI  - What are the essential symptoms in the Hoyeraal-Hreidarsson syndrome?

PMID- 9007503
TI  - Langerhans cell histiocytosis with an anterior mediastinal mass involving
      calcification: confirmation by needle biopsy.

PMID- 9007504
TI  - NMDA receptors in the pontine brainstem are necessary for fear potentiation of
      the startle response.
AB  - The fear-potentiated startle model in rats is a valuable animal test for the
      investigation of the neural and neurochemical basis of fear. In this model, rats
      are trained to associate a neutral stimulus with an aversive stimulus, so that
      after conditioning the conditioned stimulus alone elicits a state of fear leading
      to an exaggerated acoustic startle response. The fear-potentiated startle model
      does not require instrumental responding for the indication of states of fear.
      The acoustic startle response is mediated by a simple brainstem circuit, with the
      caudal pontine reticular nucleus as an interface that receives input from startle
      enhancing circuits. In the present study, we tested the hypothesis that N-methyl
      D-aspartate (NMDA) receptors on neurones of the caudal pontine reticular nucleus
      are involved in the mediation of fear-potentiated startle. After fear
      conditioning, we injected the NMDA receptor antagonist DL-2-amino-5
      phosphonopentanoic acid (AP-5), into the caudal pontine reticular nucleus of
      awake rats and tested the effect on the expression of fear-potentiated startle.
      Injections of AP-5 (0.125-0.5 nmol) into the caudal pontine reticular nucleus
      dose dependently attenuated fear-potentiated startle without affecting the
      baseline amplitude of the acoustic startle response. The results suggests that,
      in the caudal pontine reticular nucleus, glutamate may mediate fear-potentiated
      startle via NMDA receptors.

PMID- 9007505
TI  - Acute phencyclidine induces aversion, but repeated phencyclidine induces
      preference in the place conditioning test in rats.
AB  - Phencyclidine (PCP) is a drug that has been widely abused in the past two
      decades. PCP produces place aversion, but not preference, in the place
      conditioning test. The present study examined PCP-induced place conditioning
      behavior in rats treated with PCP repeatedly. In naive rats, PCP (2-8 mg/kg i.p.)
      dose dependently produced place aversion, but did not produce any effect in rats
      treated with PCP (10 mg/kg i.p.) for 14 days. indicating that tolerance developed
      to PCP-induced place aversion on repeated PCP treatment. In rats treated with PCP
      (10 mg/kg i.p.) for 28 days, PCP (2-8 mg/kg i.p.) dose dependently produced place
      preference. These findings suggest that some changes in neuronal function induced
      by the repeated PCP treatment may play an important role in the addiction to this
      drug.

PMID- 9007506
TI  - Potentiation of delta 9-tetrahydrocannabinol-induced analgesia by morphine in
      mice: involvement of mu- and kappa-opioid receptors.
AB  - The antinociceptive effect of peripheral delta 9-tetrahydrocannabinol was
      examined in mice previously treated with an inactive dose of morphine. The ED50
      of delta 9-tetrahydrocannabinol was significantly reduced by morphine, both in
      the tail-flick test (0.85 vs. 2.10 mg/kg) and in the hot-plate test (1.51 vs.
      4.71 mg/kg and 0.73 vs. 2.47 mg/kg in jumping and paw-lick responses,
      respectively). The synergistic effect between morphine and delta 9
      tetrahydrocannabinol was partially blocked by the cannabinoid receptor
      antagonist, SR-141,716 A [(N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichorophenyl)
      4-methyl-3 -pyrazolecarboxamide, hydrochloride)], at a dose of 2 mg/kg (i.p.) as
      well as by the opioid receptor antagonist naloxone, at the dose of 1 mg/kg
      (s.c.). Such an effect was also blocked by i.t. nor-binaltorphimine (a kappa
      selective opioid receptor antagonist) given at 20 micrograms/mouse as well as by
      beta-funaltrexamine (a mu-selective opioid receptor antagonist) at a dose of 2
      nmol/mouse (i.c.v., 24 h before the test). Accordingly, the mu-opioid receptor
      agonist DAMGO ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin) potentiated the effect of
      delta 9-tetrahydrocannabinol. These data show that the synergism between morphine
      and delta 9-tetrahydrocannabinol appears to involve cannabinoid as well as mu
      supraspinal and kappa-spinal opioid receptors.

PMID- 9007507
TI  - Tolerance to nicotine's effects on striatal dopamine metabolism in nicotine
      withdrawn mice.
AB  - After 7-week chronic administration of nicotine to mice in their drinking water,
      nicotine was withdrawn for 24 h. Acute nicotine challenge (1 mg/kg s.c., 60 min)
      elevated the striatal concentrations of dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA) and decreased the concentration of 3-methoxytyramine
      significantly less in the mice withdrawn for 24 h from nicotine than in the
      control mice which had been drinking tap water under identical conditions for 7
      weeks. Neither withdrawal nor the acute nicotine challenge altered the striatal
      dopamine concentration. No alterations were found in the density or affinity of
      the specific binding of [3H]SCH 23390 or [3H]spiperone to striatal membrane
      homogenates during nicotine treatment or after its withdrawal. Thus, our results
      show that tolerance to the acute effects of nicotine on striatal dopamine
      metabolism can be induced by administering nicotine to mice in the drinking
      water. However, neither chronic nicotine treatment nor its withdrawal seem to
      affect dopamine D1 and D2 receptors in the striatum.

PMID- 9007508
TI  - Anxioselective properties of 6,3'-dinitroflavone, a high-affinity benzodiazepine
      receptor ligand.
AB  - 6,3'-Dintroflavone is a synthetic flavone derivative with high affinity for
      central benzodiazepine receptors that has anxiolytic effects. Here, we describe
      its biochemical and pharmacological characterization. 6,3'-Dinitroflavone
      inhibited differentially [3H]flunitrazepam binding to central benzodiazepine
      receptors in several brain regions, showing a lower Ki value in the cerebellum
      (central benzodiazepine receptor type I-enriched area), and a higher Ki value in
      the spinal cord and in the dentate gyrus (central benzodiazepine receptor type II
      enriched area). When i.p. injected in mice, 6,3'-dinitroflavone had a potent
      anxiolytic effect in the elevated plus maze test. This effect was blocked by the
      specific central benzodiazepine receptor antagonist, Ro 15-1788. 6,3'
      Dinitroflavone did not exhibit anticonvulsant or myorelaxant effects in mice or
      amnestic effects in rats. Moreover, it abolished the myorelaxant effect of
      diazepam. On the other hand, 6,3'-dinitroflavone possessed a mild sedative action
      only at doses 100-300-fold greater than the anxiolytic one. Based on these
      findings, we suggest that 6,3'-dinitroflavone has a benzodiazepine partial
      agonist profile, with low selectivity for central benzodiazepine receptor types I
      and II.

PMID- 9007509
TI  - Chronic repeated cocaine administration increases dopamine D1 receptor-mediated
      signal transduction.
AB  - Alteration in dopamine D1 receptor-mediated signal transduction following
      repeated cocaine administration was investigated. Male Fischer rats were
      administered saline or cocaine HC1 (15 mg/kg, i.p.) three times daily at 1-h
      intervals for 1, 7, or 14 days. Stimulation of adenylyl cyclase activity by
      dopamine and the selective dopamine D1 receptor agonist, (+/-)-6-chloro-7,8
      dihydroxy-3-allyl-1-phenyl-2, 3,4,5-tetra-hydro-1 H-3-benzazepine hydrobromide
      (SKF 82958), was significantly greater in the nucleus accumbens and caudate
      putamen of animals injected with cocaine for 14 days compared with control
      animals, but was unchanged in animals administered cocaine for 1 or 7 days. These
      results suggest that dopamine D1 receptor signal transduction in the nucleus
      accumbens and caudate putamen is enhanced following chronic repeated
      administration of cocaine.

PMID- 9007510
TI  - Dipyrone into the nucleus raphe magnus inhibits the rat nociceptive tail-flick
      reflex.
AB  - Recent studies suggest that non-steroidal anti-inflammatory drugs have central
      sites of action which contribute to their analgesic efficacy. In the present
      study microinjections of the non-steroidal anti-inflammatory drug, dipyrone, were
      made into the medullary nucleus raphe magnus of lightly pentobarbital
      anesthetized rats; 25, 50, 100 and 200 micrograms of dipyrone dose-dependently
      inhibited the nociceptive tail-flick withdrawal reflex. These results suggest
      that dipyrone modulates bulbospinal neurons in the nucleus raphe magnus to
      inhibit spinal nociceptive reflexes; thus, new routes of administration and
      methods of application may be possible for these analgesic agents.

PMID- 9007512
TI  - L- and D-S-nitroso-beta,beta-dimethylcysteine differentially increase cGMP in
      cultured vascular smooth muscle cells.
AB  - We examined the effects of the L- and D-isomers of S-nitroso-beta,beta
      dimethylcysteine (L- and D-S-nitrosopenicillamine, 10(-7)-10(-5) M) on the
      guanosine 3',5'-cyclic monophosphate (cGMP) content of cultured porcine aortic
      smooth muscle cells and the decomposition of these stereoisomers to nitric oxide
      (NO). L-S-nitrosopenicillamine was a more potent generator of cGMP than D-S
      nitrosopenicillamine although both stereoisomers equally decomposed to NO. The
      10(-7) M concentration of L- or D-S-nitrosopenicillamine did not generate
      detectable amounts of NO although 10(-7) M L-S-nitrosopenicillamine but not D-S
      nitrosopenicillamine generated significant amounts of cGMP. This study shows that
      the stereoisomeric configuration of S-nitrosopenicillamine is an important factor
      in its biological potency. The data suggest that the extracellular or
      intracellular generation of NO is not the only mechanism by which this S
      nitrosothiol generates cGMP in vascular smooth muscle.

PMID- 9007511
TI  - Chronic treatment with typical and atypical antipsychotics increases the AMPA
      preferring form of AMPA receptor in rat brain.
AB  - We assessed the effects of chronic (21 day) administration of antipsychotic drugs
      on the density of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptor in rat brain. We used two typical antipsychotic drugs,
      haloperidol and pimozide, and two atypical antipsychotic drugs, risperidone and
      clozapine. Antipsychotic drugs as a group significantly elevated the density of
      the AMPA receptor measured with an AMPA receptor agonist ([3H]AMPA), but not with
      an AMPA receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione ([3H]CNQX). In
      all regions studied, the magnitude of the increase seen with chronic typical
      antipsychotic drugs was significantly greater than that seen with chronic
      atypical antipsychotic drugs. In frontal cortex and striatum, typical
      antipsychotics but not atypical antipsychotics elevated AMPA receptor binding
      over control. These findings suggest that antipsychotic drugs alter the agonist
      affinity of the AMPA receptor without altering the number of AMPA receptors.
      Typical antipsychotic drugs may be more potent in this effect than atypical
      antipsychotic drugs, especially in critical corticostriatal circuits.

PMID- 9007513
TI  - Interaction of 5-methyl-urapidil with alpha 1-adrenoceptors in canine blood
      vessels: impact of pacing-induced heart failure.
AB  - This study examines whether the alpha 1-adrenoceptors in canine endothelium
      denuded dorsal pedal artery and endothelium-denuded saphenous vein can be
      differentiated by 5-methyl-urapidil before (non-paced) and at end-stage heart
      failure induced by rapid ventricular pacing. Noradrenaline and phenylephrine
      produced concentration-dependent contractions of the dorsal pedal artery and the
      saphenous vein which were enhanced at end-stage heart failure. In non-paced
      animals, 5-methyl-urapidil was shown to be insurmountable against noradrenaline
      with the artery being more sensitive compared to the vein. At end-stage heart
      failure, 5-methyl-urapidil was a competitive antagonist against noradrenaline in
      both the artery and the vein with pA2 values of 8.1 (7.9-8.4) and 8.6 (8.2-9.1),
      respectively. A different antagonist profile was seen against phenylephrine.
      Similar to noradrenaline, insurmountable antagonism was observed in the artery
      and the vein before the development of heart failure. In contrast to
      noradrenaline, at end-stage heart failure, no antagonism was seen with the
      concentrations of 5-methyl-urapidil tested against phenylephrine. These results
      suggest that the mechanisms mediating contractions in the dorsal pedal artery and
      saphenous vein to noradrenaline and phenylephrine are heterogeneous and dependent
      on the heart failure state.

PMID- 9007514
TI  - Heterogeneity of glyceryl trinitrate response in isolated bovine coronary
      arteries.
AB  - Factors determining heterogeneity of response to glyceryl trinitrate in coronary
      microvessels have been extensively documented in recent years, but determinants
      of heterogeneity between conduit and large resistance vessels are poorly
      understood. The current study has characterised heterogeneity to glyceryl
      trinitrate and other vasodilators in bovine isolated proximal (4.5 mm i.d.) and
      distal (0.5 mm i.d.) segments of left anterior descending artery. Compared with
      proximal segments, distal segments were less responsive to glyceryl trinitrate
      and sodium nitroprusside, equi-responsive to S-nitroso-N-acetylpenicillamine, and
      more responsive to isoprenaline. Heterogeneity to glyceryl trinitrate was
      unaffected by the presence of the thiols (cysteine or N-acetylcysteine, 100
      microM). The results are interpreted as evidence that heterogeneity of vascular
      responsiveness to glyceryl trinitrate reflects impairment in the small artery of
      the cellular events which precede activation of the cyclic GMP pathway. An
      implication is that the impairment is not a consequence of limited thiol
      availability, and in this respect the cellular mechanism of heterogeneity differs
      from those proposed for the coronary microvasculature.

PMID- 9007515
TI  - A disturbed macrocirculatory supply as a determinant for a reduced sciatic nerve
      blood flow in diabetic rats.
AB  - The aim of this study was to evaluate macrocirculatory disturbances in relation
      to the reduced sciatic nerve blood flow seen in diabetic rats. Therefore, both
      femoral blood flow, the macrocirculatory arterial blood supply to the sciatic
      nerve, and the microcirculatory neuronal blood flow were measured. In order to
      differentiate between a direct vascular or a neuronal defect as a cause for the
      disturbed macrocirculatory blood flow the effects of the adrenocorticotropic
      hormone [ACTH]-(4-9) analogue, Org 2766, a neurotrophic compound without
      cardiovascular effects, were investigated on the femoral flow under basal as well
      as adrenergic-stimulated conditions. Adrenergic responsiveness to tyramine and
      phenylephrine effect on femoral flow was determined. Basal sciatic nerve and
      femoral blood flow were reduced by 48% and 42%, respectively, after 12 weeks of
      diabetes, without effect on blood pressure. Treatment with Org 2766, beginning 6
      weeks after the induction of diabetes, had no influence on these basal
      haemodynamic variables. Femoral flow in diabetic rats showed a smaller response
      to tyramine and phenylephrine compared to the control. Org 2766 restored this
      disturbed flow response to that of the control rats. In conclusion, the decrease
      in basal femoral flow might be responsible for the lowered sciatic nerve blood
      flow. Although neuronal disturbances due to diabetes had a very minor role in the
      reduction of basal femoral blood flow the adrenergic-stimulated flow
      responsiveness was seriously affected in diabetic rats.

PMID- 9007516
TI  - Investigation of the subtype of alpha 2-adrenoceptor mediating pressor responses
      in the pithed rat.
AB  - We have investigated the subtype of alpha 2-adrenoceptor mediating postjunctional
      pressor responses in the pithed rat in comparison with alpha 2-adrenoceptor
      ligand binding sites. In pithed rats, postjunctional alpha 2-adrenoceptors were
      investigated in terms of the ability of alpha 2-adrenoceptor antagonists to shift
      the pressor potency of the alpha 2-adrenoceptor agonist xylazine. Antagonist
      potency at postjunctional alpha 2-adrenoceptors in the pithed rat was correlated
      with antagonist affinity at alpha 2-adrenoceptor ligand binding sites in
      membranes of rat kidney (alpha 2B), Sf9 cells expressing human recombinant
      receptors (alpha 2C) and rat submandibular gland (alpha 2D) labelled with
      [3H]yohimbine. The correlation with the postjunctional alpha 2-adrenoceptor
      mediating pressor responses in the pithed rat was better for the alpha 2D
      adrenoceptor ligand binding site of rat submandibular gland (r = 0.95, n = 9, P <
      0.0001) and the alpha 2B-adrenoceptor ligand binding site of rat kidney (r =
      0.90, n = 9, P < 0.001) than with the human recombinant alpha 2C-adrenoceptor
      ligand binding site (r = 0.81, n = 9, P < 0.01). When the pressor potencies of
      three additional antagonists were included in the correlations for alpha 2B- and
      alpha 2D-sites only, the correlation with alpha 2D-adrenoceptor ligand binding
      site of rat submandibular gland (r = 0.91, n = 12, P < 0.0001) was much better
      than with the alpha 2B-adrenoceptor ligand binding site of rat kidney (r = 0.77,
      n = 12, P < 0.01). It is concluded that the functional postjunctional alpha 2
      adrenoceptors mediating pressor responses in the pithed rat most closely resemble
      the alpha 2D-adrenoceptors subtype.

PMID- 9007517
TI  - Lack of endothelin ETB receptor-mediated smooth muscle hyperpolarization in rat
      mesenteric resistance arteries.
AB  - The presence of functional endothelin ETB receptors was investigated in rat
      isolated mesenteric resistance arteries. Neither endothelin-3 (0.1-100 nM) nor
      the endothelin ETB selective agonists sarafotoxin S6c and BQ 3020 (both 1-100 nM)
      induced any measurable hyperpolarization or relaxation in stimulated (alpha 1
      adrenoceptor agonist; phenylephrine) or unstimulated arteries. In both cases, the
      subsequent addition of acetylcholine (1 microM) hyperpolarized the membrane
      potential by 10-20 mV and totally reversed any contraction which was present.
      These results indicate that the endothelin ETB-mediated vasodilatation observed
      in the intact mesenteric bed does not reflect hyperpolarization of smooth muscle
      cells in resistance arteries arising from the mesenteric artery.

PMID- 9007518
TI  - Potent inhibition of angiogenesis by wortmannin, a fungal metabolite.
AB  - Wortmannin ([1S-(1 alpha, 6b alpha, 9a beta, 11 alpha, 11b beta)]-11-(acetyloxy)
      1,6b,7,8,9a,10,11,11b-octahydro-1- (methoxymethyl)-9a, 11b-dimethyl-3 H
      furo[4,3,2-de]indeno[4,5-h]-2-benzopyran-3,6,9-trione), a fungal metabolite that
      is as a selective inhibitor of phosphatidylinositol 3-kinase, was evaluated for
      its potential as an inhibitor of in vivo angiogenesis in a bioassay system
      involving growing chick embryo chorioallantoic membranes. It showed dose
      dependent inhibitory activity against embryonic angiogenesis. This inhibition
      occurred at a dose as low as 1 ng (2.3 pmol) per egg and the ID50 value was 30
      ng/egg. These findings suggest that wortmannin is a new angiogenesis inhibitor,
      and that it may be a lead antibiotic for a novel class of therapeutic agents for
      angiogenesis-dependent diseases like cancer, diabetic retinopathy and rheumatoid
      arthritis.

PMID- 9007519
TI  - Regulation of intracellular Ca2+ by 8-bromoguanosine 3':5'-cyclic monophosphate,
      felodipine and ryanodine in rat caudal artery.
AB  - 45Ca2+ efflux in isolated rat caudal artery was measured in the absence and
      presence of 8-bromoguanosine 3':5'-cyclic monophosphate (8-Br-cGMP), felodipine
      or ryanodine after stimulation of alpha 1-adrenoceptors. The objectives of this
      study were to identify the mechanisms of action of 8-Br-cGMP, felodipine and
      ryanodine in a vascular resistance vessel. 8-Br-cGMP and ryanodine but not
      felodipine increased basal 45Ca2+ efflux. Phenylephrine-induced 45Ca2+ efflux was
      reduced by all three antagonists. The results of this study demonstrate that, (1)
      8-Br-cGMP-mediated relaxation is affected in part by an increased extrusion of
      intracellular Ca2+ and/or inhibition of intracellular Ca2+ release, (2) the
      Ca(2+)-channel antagonist, felodipine, impairs intracellular Ca2+ release and (3)
      ryanodine reduced phenylephrine-induced Ca2+ efflux by depleting intracellular
      Ca2+ stores.

PMID- 9007520
TI  - The aldose reductase inhibitor sorbinil does not prevent the impairment in nitric
      oxide-mediated neurotransmission in anococcygeus muscle from diabetic rats.
AB  - This study investigated whether increased polyol pathway activity could
      contribute to alterations in nitrergic neurotransmission in anococcygeus muscles
      from 8-week diabetic rats. In the presence of guanethidine (10-30 microM) and
      clonidine (0.01-0.05 microM), relaxations obtained to nitrergic nerve stimulation
      (0.5-5 Hz, 10-s train), to sodium nitroprusside (5-500 nM) and to nitric oxide
      (0.1-3 microM) were significantly reduced in muscles from diabetic rats compared
      to responses from control rats. Treatment of diabetic rats with the aldose
      reductase inhibitor sorbinil (42 mg/kg per day via feed for 8 weeks) did not
      affect impaired reactivity to nitrergic nerve stimulation, sodium nitroprusside
      or nitric oxide. The results suggest increased polyol pathway activity does not
      contribute to the alterations in nitrergic neurotransmission in anococcygeus
      muscles from diabetic rats.

PMID- 9007521
TI  - Cyclopiazonic acid-induced changes in contractile activity of smooth muscle
      strips isolated from cat and guinea-pig stomach.
AB  - The effects of cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic
      reticulum Ca(2+)-ATPase, on contractile activity of circular smooth muscle strips
      isolated from the antrum, corpus and fundus regions of the cat and guinea-pig
      stomach were studied. Contractile activity was recorded under isometric
      conditions, in organ baths. CPA, concentration dependently (3 x 10(-7)-3 x 10(-5)
      M) increased the tone of the cat and guinea-pig gastric fundus and corpus as well
      as the amplitude of the phasic contractions of the cat corpus and antrum,
      affecting their frequency. CPA had a dual action on the phasic contractions of
      the guinea-pig antrum: an increase at low concentrations (up to 10(-6) M) and
      inhibition at high concentrations (10(-6)-3 x 10(-5) M). Tetrodotoxin (10(-6) M),
      atropine (10(-6) M) and N omega-nitro-L-arginine (10(-4) M) did not change
      significantly the effects of CPA. Nifedipine completely inhibited the CPA-induced
      phasic contractions and partly inhibited the CPA-induced tonic contractions. The
      nitric oxide-releasing agents, sodium nitroprusside (10(-3) M) and 3-morpholino
      sydnonimine (10(-3) M), completely inhibited the CPA-induced tonic and phasic
      contractions. CPA induced tonic contractions in the cat and guinea-pig gastric
      fundus precontracted by acetylcholine (10(-5) M) and inhibited the acetylcholine
      (10(-6) M)-induced phasic contractions in the guinea-pig gastric antrum and
      corpus. The results suggest multiple roles for sarcoplasmic reticulum Ca2+ stores
      and sarcoplasmic reticulum Ca(2+)-ATPase in the shaping of spontaneous and evoked
      tonic and phasic contractions of the stomach, and highlight important species and
      tissue differences.

PMID- 9007523
TI  - Effect of short- and long-acting beta 2-adrenoceptor agonists on pulmonary beta 2
      adrenoceptor expression in human lung.
AB  - beta-Adrenoceptor agonists induce the down-regulation of beta 2-adrenoceptors and
      mRNA expression in animal lung. The down-regulation of beta 2-adrenoceptors may
      limit the therapeutic efficacy of beta 2-adrenoceptor-mediated bronchodilators in
      obstructive airways disease. We examined the effects of three selective beta 2
      adrenoceptor agonists, salbutamol, salmeterol and formoterol on beta 2
      adrenoceptor binding and mRNA levels in human lung in vitro. Human lung was
      obtained from cardiac transplantation donors. Peripheral lung was chopped and
      incubated with three selective beta 2-adrenoceptor agonist for 3 h or 24 h at
      three different concentrations (0.1, 1 and 10 microM). The affinity and density
      of beta 2-adrenoceptors was determined by [125I]iodocyanopindolol equilibrium
      binding in a lung membrane preparation in the presence of 0.1 microM CGP 20712 A
      (1-{2-[(3-carbamoyl-4-hydroxy)phenoxy] ethylamino}-3-[4-(1-methyl-4
      trifluoromethyl-2-imidazolyl) phenoxy]-propan-2-ol), a selective beta 1
      adrenoceptor antagonist. Although treatment with salbutamol for 3 h did not
      change beta 2-adrenoceptor density, both salmeterol and formoterol reduced beta 2
      adrenoceptor density, and exposure to each agonist for 24 h reduced beta 2
      adrenoceptor density at all concentrations. Treatment with 10 microM salmeterol
      increased the equilibrium dissociation constant (Kd), and also shifted the
      competition curves of (-)-isoprenaline to the left, beta 2-Adrenoceptor mRNA,
      measured by Northern blot analysis using a human beta 2-adrenoceptor cDNA probe,
      was reduced after exposure to all beta 2-adrenoceptor agonists at 3 h. Our data
      provide evidence for down-regulation of beta 2-adrenoceptor protein and mRNA
      after selective beta 2-adrenoceptor agonist treatment in human lung.

PMID- 9007522
TI  - NS-49, an alpha 1A-adrenoceptor agonist, selectively increases intraurethral
      pressure in dogs.
AB  - The effects of NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane
      sulfonanilide hydrochloride), an alpha 1A-adrenoceptor-selective agonist, on
      intraurethral pressure and blood pressure were investigated in anesthetized dogs.
      In addition, the contractile effects of NS-49 on the isolated dog urethra and
      carotid artery were compared with those of non-selective alpha 1-adrenoceptor
      agonists. Intravenously (i.v.) administered NS-49 at 0.3 microgram/kg or more
      significantly increased intraurethral pressure in a dose-dependent manner. Much
      higher doses of NS-49 were needed to increase blood pressure. In contrast, ST
      1059 (1-(2',5'-dimethoxyphenyl)-2-aminoethanol) (an active metabolite of
      midodrine) at 30 micrograms/kg or more significantly increased both intraurethral
      pressure and blood pressure. NS-49 was 11-fold more selective for intraurethral
      pressure than ST-1059, NS-49, ST-1059, phenylephrine and noradrenaline caused
      concentration-dependent contraction of the isolated dog urethra. NS-49 caused
      only a slight contraction of the dog carotid artery even at high concentrations,
      whereas the reference drugs caused contractions of the artery with high efficacy.
      The alpha 1A-adrenoceptor-selective antagonists 5-methyl-urapidil and WB-4101
      also showed high affinity for alpha 1-adrenoceptors in the dog urethra in
      inhibiting [3H]prazosin binding. In conclusion, the alpha 1A-selective agonist NS
      49 selectively increased intraurethral pressure in dogs, and produced selective
      contraction of the dog urethra. These results suggest that the alpha 1A
      adrenoceptor subtype is responsible for the contraction of the urethra and the
      regulation of intraurethral pressure, and that NS-49 might be useful for the
      treatment of stress incontinence with little effect on the cardiovascular system.

PMID- 9007524
TI  - Dysfunctional muscarinic M2 autoreceptors in vagally induced bronchoconstriction
      of conscious guinea pigs after the early allergic reaction.
AB  - We studied the function of autoinhibitory muscarinic M2 receptors on vagal nerve
      endings in the airways of conscious, unrestrained, ovalbumin-sensitized guinea
      pigs after the early and late allergic reaction. For this purpose, the effects of
      the selective muscarinic M2 receptor antagonist gallamine were examined on
      unilateral vagus nerve stimulation-induced bronchoconstriction, which was
      determined as an increase in basal respiration amplitude, measured as changes in
      pleural pressure. Under control conditions, i.e., before antigen challenge, a
      significant increase in the pleural pressure was found after inhalation of 0.1 mM
      and, even more pronounced, 1.0 mM gallamine, at medium stimulation frequencies (2
      16 Hz), leading to a leftward shift of the frequency-response curve. After
      inhalation of 10 mM of gallamine, a complete reversal of the left-shift was
      observed and the frequency-response curve was depressed. However, 6 h after
      challenge with ovalbumin (i.e., after the early allergic reaction) no increase in
      nerve stimulation-induced bronchoconstriction by gallamine was found; a decrease
      in this bronchoconstriction was again observed with the highest concentration. At
      this moment, bronchial responsiveness to histamine was enhanced 4.5-fold compared
      to control, i.e., prior to antigen provocation. Both after the late allergic
      response (24 h after challenge; 1.6-fold histamine hyperresponsiveness) and 4
      days after allergen challenge (normal histamine responsiveness) the gallamine
      induced potentiation of the bronchoconstriction was restored, similar to the
      responses under control conditions. The results clearly demonstrate that
      prejunctional muscarinic M2 receptors control bronchoconstriction in conscious,
      unrestrained guinea pigs in vivo. Furthermore, these autoinhibitory receptors
      appear to be completely dysfunctional after the early allergic phase, but their
      function is largely restored after the late phase. The results indicate that
      dysfunction of autoinhibitory muscarinic M2 receptors might contribute to the
      strongly enhanced responsiveness to histamine after the early allergic response.

PMID- 9007525
TI  - Response heterogeneity of 5-HT3 receptor antagonists in a rat visceral
      hypersensitivity model.
AB  - Subcutaneous administration of granisetron (BRL 43694, endo-1-methyl-N-(9-methyl
      9-azabicyclo[3.3.1.]non-3-yl-1 H-indazole-3-carboxamide) and zacopride (4-amino-N
      (1-azabicyclo[2.2.2.]oct-3-yl)-5-chloro-2-methoxybenzamide), two 5-HT3 receptor
      antagonists, at doses ranging from 3 to 1000 micrograms/kg, inhibited abdominal
      contractions induced by distension (30 mmHg, 10 min) of irritated colon (0.6%
      acetic acid) in conscious rats with a bell-shaped dose-response curve. The ED50
      of granisetron and zacopride were 17.6 and 8.2 micrograms/kg, respectively. In
      contrast, both tropisetron (ICS 205-930, (3-a-tropanyl)t-indole-3-carboxylic
      ester) and ondansetron (GR38032F, 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1 H
      imidazol-1-yl)methyl]-4 H-carbazol-4-one hydrocloride dihydrate) were inactive in
      this model. These data further support the concept of a heterogeneity in the
      potency of 5-HT3 receptor antagonists in modulating visceral hypersensitivity in
      conscious rats. This finding is in agreement with a reported efficacy of
      granisetron but not of ondansetron in patients with irritable bowel syndrome.

PMID- 9007526
TI  - Vanadyl sulphate differently influences insulin response to glucose in isolated
      pancreas of normal rats after in vivo or in vitro exposure.
AB  - The effect of the antidiabetic agent vanadyl sulphate (VOSO4) on the endocrine
      pancreas function of normal rats was studied using the isolated pancreas
      preparation. A short-term (8 days) i.p. treatment (15 mg/kg per day) resulted in
      attenuation of high glucose-stimulated insulin release, at day 9 but also at days
      19, i.e., after full recovery of appetite and weight, while blood and pancreas
      vanadium concentrations were still elevated. Six months of oral VOSO4 treatment
      (0.75 mg/ml in drinking water) resulted in elevated vanadium concentrations while
      glucose-stimulated insulin release was attenuated as compared to pair-fed
      animals. Conversely, when directly perfused in pancreas, VOSO4 potentiated
      glucose-stimulated insulin release. These apparently opposite effects may be
      related to the ability of VOSO4 to exert both peripheral insulinomimetic effects
      leading to chronic reduction in insulin demand-, and a direct pancreatic
      insulinotropic activity.

PMID- 9007527
TI  - Leukocyte integrin very late antigen-4/vascular cell adhesion molecule-1 adhesion
      pathway in splanchnic artery occlusion shock.
AB  - We investigated the role played by the very late antigen-4 (VLA-4)/ vascular cell
      adhesion molecule-1 (VCAM-1) interaction in the pathogenesis of splanchnic artery
      occlusion shock. Splanchnic artery occlusion shock was induced in anaesthetized
      rats by clamping splanchnic arteries for 45 min. Sham operated animals were used
      as controls. Survival time, serum tumour necrosis factor (TNF-alpha), monocyte
      and lymphocyte cell count and the responsiveness to acetylcholine of aortic rings
      were studied. Furthermore we investigated the VCAM-1 expression on vessel
      endothelium and the percentage of VLA-4 positive leukocytes. Splanchnic artery
      occlusion shocked rats had a decreased survival time (76 +/- 10 min, while sham
      shocked rats survived more than 4 h), increased serum levels of TNF-alpha (328 +/
      11 U/ml), a decreased number of both monocytes and lymphocytes and reduced
      responsiveness to acetylcholine (10 nM-10 microM) of aortic rings. In addition we
      found an increased expression of endothelial VCAM-1 on aortic rings and a reduced
      percentage of VLA-4 positive lymphocytes and monocytes. Passive immunization with
      specific antibodies raised against either VCAM-1 or VLA-4 (2 mg/kg, i.v., 3 h
      before splanchnic artery occlusion shock) increased survival, improved monocyte
      and lymphocyte count and restored the responsiveness of aortic rings to
      acetylcholine (P < 0.01). Finally, inhibition of TNF-alpha biosynthesis reversed
      the increased endothelial expression of VCAM-1 and the reduced percentage of
      integrin VLA-4 positive leukocytes. Our findings suggest that (i) VLA-4/VCAM-1
      interaction has a role in the pathogenesis of circulatory shock; (ii) this
      interaction might be a target for new therapeutic approaches to the therapy of
      low-flow states.

PMID- 9007528
TI  - Expression of mu-, delta- and kappa-opioid receptors in baculovirus-infected
      insect cells.
AB  - The mu-, delta- and kappa-opioid receptors have been expressed in Sf9 and 'High
      Five' insect cells using the baculovirus expression system. In both cell lines
      highest receptor levels (pmol/mg membrane protein) were observed 48 h after
      infection. Concomitant exposure to the narcotic antagonist naloxone (1 microM)
      enhanced the production of each receptor type. However, "High Five' cells
      differed from Sf9 cells in a 2-3-fold higher receptor density in the cell
      membrane and were therefore employed for receptor characterization. In membranes
      of 'High Five' cells opioid receptor levels ranged from 1.0 +/- 0.2 pmol/mg
      protein for the kappa-opioid receptor, 1.7 +/- 0.2 pmol/mg for the delta-opioid
      receptor to 2.1 +/- 0.5 pmol/mg for the mu-opioid receptor. The mu-, delta- and
      kappa-opioid receptor agonists [D-Ala2,N-methyl-Phe4-Gly-ol5]enkephalin
      ([3H]DAMGO), [D-Pen2,D-Pen5]enkephalin ([3H]DPDPE) and (5 alpha, 7 alpha, 8 beta)
      (+)-N-methyl-N-(7-(1-pyrrolidinyl-1-oxaspiro(4,5)dec-8-yl) benzeneacetamide
      ([3H]U69,563) bound to the opioid receptors with Kd values of 3.4 +/- 0.3 nM, 4.5
      +/- 0.1 nM and 1.2 +/- 0.3 nM, respectively, resembling those reported for opioid
      receptors expressed in mammalian cells. Testing the functionality of the
      receptors in 'High Five' cells, we found that high affinity agonist binding was
      strongly reduced in the presence of GTP gamma S/sodium, indicating their coupling
      to G proteins. Furthermore, activation of the three receptor types inhibited
      forskolin-stimulated cAMP formation. The results presented here suggest that the
      'High Five' cell/baculovirus system provides a convenient method for high level
      expression of functionally intact opioid receptors as judged by receptor binding
      studies, their G-protein coupling and inhibition of adenylyl cyclase.

PMID- 9007529
TI  - Low levels of hydrogen peroxide and L-histidine induce DNA double-strand breakage
      and apoptosis.
AB  - The results presented in this study demonstrate that L-histidine triggers a
      lethal response in U937 cells exposed to nontoxic, albeit growth-inhibitory,
      levels of H2O2. Treatment for 1 h with the cocktail H2O2/L-histidine promotes the
      formation of a low level of DNA double-strand breaks that are rapidly rejoined,
      and this process is followed by secondary DNA fragmentation at about 7 h of post
      treatment incubation, at which time cells are still viable. The appearance of
      oligonucleosomal DNA fragments associated with the detection of morphological
      changes typical of apoptosis strongly suggests that a portion of the cells was
      undergoing an apoptotic process. The relative level of cells with fragmented
      chromatin never exceeded 15-20% throughout the 20 h post-treatment incubation.
      Treatment with high concentrations of H2O2 in the presence of L-histidine was
      found to trigger necrotic cell death. The results presented in this paper provide
      further experimental evidence in support of the notion that DNA double-strand
      breaks mediate the lethal effects of the cocktail H2O2/L-histidine and suggest
      that this type of DNA lesion can promote both apoptotic and necrotic cell death,
      depending on the concentration of the oxidant.

PMID- 9007530
TI  - Functional characterisation of alpha 1-adrenoceptor subtypes mediating
      noradrenaline-induced inositol phosphate formation in rat thalamus slices.
AB  - In cross-chopped slices from rat thalamus and in the presence of 10 mM LiCl,
      noradrenaline stimulated the accumulation of [3H]inositol phosphates with
      [3H]inositol monophosphates ([3H]IP1) being the major product detected (86 +/- 2%
      of total [3H]inositol phosphates). Noradrenaline-induced [3H]IP1 accumulation was
      concentration-dependent and yielded and EC50 of 4.6 +/- 0.2 microM, maximum
      effect of 272 +/- 3% of basal formation and Hill coefficient (nH) of 1.6 +/- 0.1.
      The effect of 100 microM noradrenaline was inhibited by the alpha 1-adrenoceptor
      antagonists prazosin, (+)-niguldipine, 5-methylurapidil and WB-4101 (2-(2,6
      dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane). The inhibition curve for
      prazosin best fit to a single-site model whereas curves for (+)-niguldipine, 5
      methylurapidil and WB-4101 best fit to a two-site model. The putative alpha 1D
      adrenoceptor-selective antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-8- azaspiro[4.5]decane-7,9-dione) showed low potency and
      efficacy to inhibit the response to noradrenaline. Pre-treatment of the slices
      with chloroethylclonidine (100 microM; 30 min) decreased by 64 +/- 4% the maximum
      response. Noradrenaline-induced [3H]IP1 accumulation was significantly reduced by
      Ca2+ removal (by 64 +/- 2%) and by the Ca(2+)-channel blockers Ni2+, Co2+ and
      nimodipine (inhibition of 56 +/- 6%, 54 +/- 5% and 41 +/- 5%, respectively).
      Taken together these results indicate that noradrenaline-induced inositol
      phosphate formation in thalamus slices is mainly mediated by the activation of
      both alpha 1B and alpha 1A subtypes of alpha 1-adrenoceptors.

PMID- 9007531
TI  - Histamine H1 receptor activation stimulates [3H]GABA release from human
      astrocytoma U373 MG cells.
AB  - In U373 MG cells, a line derived from a human astrocytoma, histamine stimulated
      the release of [3H]gamma-aminobutyric acid ([3H]GABA) in a concentration
      dependent manner (286 +/- 23% of basal release at 1 mM histamine). Neither Ca2+
      removal nor Cd2+ (100 microM) affected [3H]GABA release evoked by 100 microM
      histamine but the response was significantly reduced by 10 microM U-73122 ({1-[6
      ((17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl)-amino)-hexyl]-1 H-pyrrole-2,5
      dione}), an inhibitor of phospholipase C activation (79 +/- 8% inhibition) and by
      10 microM dimethylbenzamil, a selective blocker of plasma membrane Na+/Ca2+
      exchange (58 +/- 6% inhibition). In [3H]inositol-labelled cells histamine
      stimulated [3H]inositol phosphate accumulation (EC50, 17 +/- 2 microM; maximum
      effect, 203 +/- 4% of basal). Histamine-evoked Ca2+ mobilisation yielded an EC50
      of 12 +/- 2 microM and maximum delta[Ca2+]i of 337 +/- 23 nM. Thapsigargin (1 nM)
      increased [Ca2+]i (delta[Ca2+]i 164 +/- 12 nM) and prevented any further increase
      by histamine (100 microM). The effects of histamine on [3H]GABA release,
      [3H]inositol phosphate accumulation and Ca2+ mobilisation were blocked by the
      selective histamine H1 receptor antagonist mepyramine. Taken together, these
      results indicate that histamine stimulates [3H]GABA release by increasing
      [Ca2+]i. The mechanism of release may be related to changes in transmembranal Na+
      gradients and reversal of GABA carrier transport due to stimulation of plasma
      membrane Na+/Ca2+ exchange.

PMID- 9007532
TI  - Differences in cation sensitivity of ligand binding to Y1 and Y2 subtype of
      neuropeptide Y receptor of rat brain.
AB  - The binding of selective ligands to the Y1 subtype of neuropeptide Y receptor in
      rat brain particulates was promoted by Ca2+ and also stimulated by Sr2+, but
      reversibly reduced by Ba2+, Mg2+, Mn2+, by the organic polycations neomycin and
      spermidine, and by chelating agents. The alkali monovalent cations inhibited the
      Ca(2+)-enabled Y1 subtype binding with some selectivity (Cs+ > or = NH4+ > Li+ >
      Na+, K+), with half-inhibition between 70-120 mM. The specific Y2 subtype binding
      was enhanced by all alkaline-earth divalent cations, Mn2+, neomycin and
      spermidine in the range of 0.1-10 mM, and by alkali cations at up to 100 mM, and
      also by Na+ salts of the chelators EGTA and EDTA. The large disparity in cation
      sensitivity indicates substantial differences in the structure of the binding
      sites of the Y1 and Y2 receptors, predictable from known distinct features of
      ligand epitopes and of primary structure of the receptors.

PMID- 9007533
TI  - Interaction of thiocolchicoside with [3H]strychnine binding sites in rat spinal
      cord and brainstem.
AB  - Radioreceptor binding assays and receptor autoradiography were used to
      investigate the activity of thiocolchicoside on strychnine-sensitive binding
      sites in rat brain and spinal cord using [3H]strychnine as a ligand.
      Thiocolchicoside displaced the binding of [3H]strychnine with an affinity similar
      to that of unlabeled glycine, and showed a Hill coefficient and proportionality
      parameter (P) less than unity. The activity of thiocolchicoside toward
      [3H]strychnine binding sites was confirmed in autoradiographic studies. The
      results suggest that thiocolchicoside behaves as an allosteric compound acting on
      the strychnine-sensitive glycine receptor in rat brainstem and spinal cord, and
      that this may provide a possible mechanism for the myorelaxant activity of this
      colchicoside derivative, the first clinically useful drug acting on this
      receptor.

PMID- 9007534
TI  - High levels of specific neuropeptide Y/pancreatic polypeptide receptors in the
      rat hypothalamus and brainstem.
AB  - It is known that the paraventricular hypothalamic nucleus is responsible for some
      of the stimulatory effects of neuropeptide Y, peptide YY and the pancreatic
      polypeptides on food intake. However, specific neuropeptide Y Y1 and Y2 receptors
      were not abundantly expressed in the hypothalamus. In contrast, specific
      [125I]human pancreatic polypeptide binding sites were detected in this
      hypothalamic nucleus as well as the medial preoptic area, interpeduncular
      nucleus, nucleus tractus solitarius, area postrema and dorsal vagal nucleus while
      cortical areas and the hippocampus contained negligible levels of labeling. The
      ligand binding profile of the various competitors suggests that the binding sites
      labeled by [125I]human pancreatic polypeptide are predominantly of the
      neuropeptide Y Y4 and/or Y5 subtypes. These newly cloned receptors may play a key
      role in the modulatory effects of neuropeptide Y and related peptides on
      appetite.

PMID- 9007535
TI  - Rapid dendritic Ca2+ influx is associated with induction of homosynaptic long
      term depression in adult rat hippocampus.
AB  - Homosynaptic long-term depression was induced in area CA1 of adult hippocampus by
      prolonged low-frequency stimulation (900 pulses at 2 Hz) in the presence of the
      GABAA receptor antagonist picrotoxin. Using ratio imaging with fura-2, we
      demonstrate that the induction of this long-term depression is associated with a
      rapid and transient (approximately 30 s) dendritic Ca2+ increase (approximately
      500 nM) dependent on the activation of voltage-gated Ca2+ channels. This
      transient increase, by itself, was insufficient for long-term depression
      induction.

PMID- 9007536
TI  - Control of remembered reaching sequences in monkey. I. Activity during movement
      in motor and premotor cortex.
AB  - Motor and premotor cortex firing patterns from 307 single neurons were recorded
      while monkeys made rapid sequences of three reaching movements to remembered
      target buttons arrayed in two-dimensional space. A primary goal was to study and
      compare directionally tuned responses for each of three movement periods during
      12 movement sequences that uniformly sampled the directional space in front of
      the monkey. The majority of neurons showed maximal responses during movements in
      a preferred direction with smaller increases during movements close to the
      preferred direction. These responses showed a statistically significant
      regression fit to a cosine function for 72% of the neurons examined. Comparisons
      among tuning directions computed separately for the first, second, and third
      movement periods suggested the near constancy of preferred direction across a
      rapidly executed series of movements even though these movements began at
      different starting points in space. Although directionally tuned neurons were
      only broadly tuned for a specific direction of movement, the neuronal ensemble
      carried accurate directional information. A population vector computed by summing
      vector contributions from the entire population of tuned neurons predicted
      movement direction with a mean accuracy of 20 degrees. This population code made
      consistent predictions for each of the 36 movements that were studied using a
      single set of population parameters. Most of the remaining neurons (24%) that
      were not tuned during movement did show significant changes in activity during
      other aspects of task performance. Some nontuned neurons had nondirectional
      increases that were sustained during movement, while others showed identical
      phasic bursts during the three movement periods. These nontuned neurons may
      control stabilizations of the shoulder, trunk, and forearm during movement, or
      forearm movements during button pushing.

PMID- 9007537
TI  - Control of remembered reaching sequences in monkey. II. Storage and preparation
      before movement in motor and premotor cortex.
AB  - Single-neuron responses in motor and premotor cortex were recorded during a
      movement-sequence delay task. On each trial the monkey viewed a randomly selected
      sequence of target lights arrayed in two-dimensional space, remembered the
      sequence during a delay period, and then generated a coordinated sequence of
      movements to the remembered targets. Of 307 neurons studied, 25% were tuned
      specifically for either the first or the second target, but not both. In
      particular, for neurons tuned during both target presentations, tuned activity
      related to a particular first target direction were maintained during the
      presentation of a second target in a different direction. During the delay
      period, 32% of the neurons were tuned for upcoming movement in a single
      direction. These delay period responses often reflected activity patterns that
      first developed during target presentations and may therefore act to maintain
      target period information during the delay. Neurons with tuned activity during
      both the delay and movement periods exhibited two patterns: the first exhibited
      tuned responses during the delay that were correlated with the tuning of first
      movement responses, while the second pattern showed delay-period tuning that was
      better correlated with tuned responses during second movements. This indicates
      that, before movement, distinct neural populations are correlated with specific
      movements in a sequence. About half the neurons studied were not directionally
      tuned during the initiation, target, or delay periods, but did show systematic
      changes in activity during task performance. Some (34%) were exclusively tuned
      during movement and appear to be involved in the direct control of movement.
      Others (17%) showed changes in firing rate from period to period within a trial
      but showed no directional preference for a particular direction of movement.
      Population analyses of tuned activity during the target and delay periods
      indicated that accurate directional information about both first and second
      movements was available in the neuronal ensemble well before reaching began.
      These results extend the idea that both motor and premotor cortex play a role in
      reaching behavior other than the direct control of muscles. While some early
      neural responses resembled muscle activation patterns involved in maintaining
      fixed postures before movement, others probably relate to the sensory-to-motor
      transformations, information storage in short-term memory, and movement
      preparation required to generate accurate reaching to remembered locations in
      space.

PMID- 9007539
TI  - Optically induced plasticity of the cervico-ocular reflex in patients with
      bilateral absence of vestibular function.
AB  - The horizontal cervico-ocular reflex (COR) was examined in five labyrinthine
      defictive subjects (LDS), during both passive oscillations of the head on the
      trunk (HTexam) and of the trunk under the earth-fixed head (THexam) at 0.1-0.5
      Hz, peak angular displacement +/- 30 degrees. Subjects were tested in the dark,
      before and immediately after adaptation to binocular magnifying (x1.9) and
      reducing (x0.6) lenses. During long-term adaptation, the LDS were exposed to the
      normal environment for 5 h while wearing lenses. Short-term adaptation
      experiments (15-20 min) consisted of sustained ocular following of a small LED in
      an otherwise dark room and in full-room illumination. This LED was either
      stationary in space whilst the subjects moved their head actively, or fixed on
      the chair and rotating with the trunk during head-fixed stimulation. In all five
      patients, magnifying lenses increased COR gain (peak slow-phase eye velocity/peak
      stimulus velocity), whereas reducing lenses reduced the gain. Under HTexam the
      gain changes were greater, more consistent and the phases approximately
      compensatory to head displacement, whereas during THexam the gain decreased and
      phase increased at higher frequencies. COR adaptation was observed during foveal
      stimulation alone, but the effects were stronger with added background
      illumination. Results during an imaginary target task showed that the gain can be
      influenced strongly by mental set. Our findings indicate a highly modifiable COR
      in subjects with loss of vestibular function. Both peripheral and foveal retinal
      information contribute to the plastic changes in COR gain. Somatosensory cues
      from the trunk as well as cognitive/perceptual factors may be involved in the
      modification of the COR, by providing information about the relevance of eye
      movements, and contribute to the stabilisation of gaze in space.

PMID- 9007538
TI  - Altered neuronal distribution of parvalbumin in anterior cingulate cortex of
      rabbits exposed in utero to cocaine.
AB  - Previous studies of rabbits exposed in utero to cocaine have revealed an increase
      in the number of neurons which are GABA immunoreactive in the anterior cingulate
      cortex (ACC), suggesting a cocaine-elicited modification in the balance of
      excitatory and inhibitory interactions. Of the major calcium binding proteins
      expressed by different subgroups of GABAergic neurons, parvalbumin has been
      observed in conditions involving excess excitation, and may serve to protect
      neurons from excitotoxicity. In the present study, we used immunocytochemistry to
      compare the effects of prenatal cocaine exposure on the postnatal development of
      parvalbumin immunoreactivity in interneurons of the visual cortex (VC) and ACC.
      We determined the number and laminar distribution of parvalbumin immunoreactive
      neurons, and we also assessed the distribution of parvalbumin immunoreactivity
      within primary, secondary and tertiary dendrites of neurons in these two cortical
      areas. In both ACC and VC, parvalbumin immunoreactive neurons were first observed
      around postnatal day 10 (P10) and their number increased rapidly from P10 to P20.
      At all ages studied (P10 to P60) there was no difference between cocaine-exposed
      and saline control animals in the number or laminar distribution of parvalbumin
      immunoreactive neurons in either cortical area. However, the distribution of
      parvalbumin immunoreactivity within dendrites revealed a significant difference
      between cocaine-exposed and saline control animals in ACC but not in VC. In ACC,
      at all ages studied, there was an increase in the number of primary, secondary
      and tertiary dendrites which were parvalbumin immunoreactive in cocaine-exposed
      animals compared with saline controls. This difference was most striking in
      secondary dendrites, and in laminae V and VI. The effect was observed at doses of
      4 and 3 mg/kg per injection but not at 2 mg/kg per injection. In contrast to ACC,
      in VC there was no difference in the number of immunoreactive dendrites in
      cocaine-exposed animals compared with saline controls. These observations are
      consistent with the hypothesis that the ACC of rabbits exposed in utero to
      cocaine is characterized by altered excitatory/inhibitory interactions. ACC
      receives a dense dopaminergic input, but VC receives minimal dopaminergic
      innervation. Mechanisms by which the action of cocaine on the developing
      dopaminergic system may modify the balance of excitation and inhibition in ACC
      are discussed.

PMID- 9007540
TI  - Transcallosally mediated inhibition of interneurons within human primary motor
      cortex.
AB  - The objective of this study was to investigate interhemispheric transcallosal
      connections between primary motor cortices noninvasively in awake human subjects.
      For this purpose, focal transcranial magnetic stimulation was performed on eight
      healthy, right-handed subjects and one patient with congenital collosal agenesis.
      Using two magnetic stimulators, we investigated the effect of a conditioning
      magnetic stimulus applied to the motor cortex of one hemisphere on the duration
      of the silent period (SP) evoked in the first dorsal interosseus (FDI) muscle by
      a magnetic test stimulus given over the opposite motor cortex. It is well
      established that SP reflects activation of inhibitory interneurons within primary
      motor cortex. In all normal subjects, a conditioning stimulus to one hemisphere
      produced a significant shortening of SP evoked by the test stimulus when the
      conditioning-test-interval was 10-20 ms. The effect was also observed when an
      electrical test stimulus was used. The conditioning coil had to be placed over
      the hand motor area to obtain the maximal effect. The threshold for eliciting
      this decrease of SP duration was higher than the threshold for eliciting an early
      excitatory muscle response in the contralateral FDI. Increasing the intensity of
      the conditioning stimulus led to linear reduction of SP duration. In the patient
      with callosal agenesis, no such decreasing effect on SP duration was observed.
      These results suggest that inhibitory interneurons within primary hand motor
      cortex receive transcallosal inhibitory input from the opposite motor cortex. We
      propose that modulation of motor cortical interneurons via transcallosal pathways
      may provide a gain control for the motor cortical output system and subserve
      interhemispheric coordination in complex, nonsymmetrical bimanual movements.

PMID- 9007541
TI  - Changes of intracellular free calcium following mechanical injury in a spinal
      cord slice preparation.
AB  - Intracellular calcium ions are, in addition to free radicals, an important
      mediator of tissue destruction following traumatic injury to the spinal cord. In
      vivo measurements of calcium in the interstitial space and in the tissue suggest
      the occurrence of a posttraumatic shift of calcium from the extracellular to the
      intracellular compartment at the injury site. No information is, however,
      available on the posttraumatic changes of calcium in the intracellular
      compartment, where the ion exerts its crucial messenger function. We developed an
      in vitro model of local traumatic spinal injury, using a spinal cord slice
      preparation, allowing us to investigate injury-related changes of intracellular
      free calcium. The injury consisted of the impact of a small needle, and
      intracellular free calcium was measured with fura-2. Application of the injury at
      different places within the gray matter caused a transient and reproducible
      increase in the fura-2 fluorescence ratio. This injury-induced ratio increase was
      largely, but not completely, suppressed under zero extracellular calcium
      conditions. It was also largely depressed in the presence of high extracellular
      potassium and in the absence of extracellular sodium. It was modestly depressed
      by the calcium channel blocker nifedipin, by the calcium release channel blocker
      dantrolene, and by the gap junction blockers halothane and octanol. The calcium
      channel blocker flunarizine, the N-methyl D-aspartate (NMDA)-receptor-channel
      blocker MK-801 and the endoplasmic reticulum calcium-ATPase blocker thapsigargin
      had no effect. The experiments suggest that injury is associated with an increase
      in intracellular free calcium that is mediated by calcium influx, in part via L
      type calcium channels. They furthermore give evidence that sodium influx and gap
      junctions are involved in these injury-associated changes of intracellular free
      calcium.

PMID- 9007543
TI  - Visual and vestibular factors influencing vestibular "navigation".
AB  - In order to elucidate the role of the "starting point" in path integration,
      normal subjects underwent a self-rotational task in a motor-driven turntable
      rotating around an earth-vertical axis. They were passively rotated ("stimulus")
      and had to return to the starting point, controlling the direction and velocity
      of the turntable by means of a joystick ("response"). The test included
      conditions with an earth-fixed target (EFT) as starting point, shown before the
      stimulus, and conditions without EFT presentation. The subject's response always
      took place in total darkness. Subjects succeeded in returning to the starting
      point in all conditions but were more precise (i.e. had smaller variability of
      responses) with the EFT than in the other conditions. The larger data scatter
      (inaccuracy) in these latter tasks was directly related to the return peak
      velocity, whereas with EFT there was no relationship between amplitude and
      velocity of the return motion. These results suggest that the presentation of the
      starting point (the EFT) allows a real time integration to take place, thereby
      improving accuracy during self-controlled motion in the dark. Five subjects were
      also tested with the same rotational paradigm in total darkness throughout, but
      with the head in a different position during stimulus and response motions. Thus,
      motion detection was performed by different semicircular canals during stimulus
      and response. The conditions used were head upright during stimulus, hyper
      extended backward during response motion, and head backward during stimulus and
      upright during response motion. It was found that the accuracy during these tasks
      did not differ from that during stimulus/response motion without change in the
      upright or backward head position. These data indicate that estimates of
      trajectory are, within limits, independent of canal plane.

PMID- 9007542
TI  - Effects of perinatal asphyxia on the mesostriatal/mesolimbic dopamine system of
      neonatal and 4-week-old male rats.
AB  - The present study was undertaken in order to study the effects of perinatal
      asphyxia on tyrosine hydroxylase (TH) activity, dopamine levels and turnover, and
      dopamine metabolites (3,4-dihydroxyphenylacetic acid, DOPAC, homovanillic acid,
      HVA, and 3-methoxytyramine, 3-MT, analyzed by high-performance liquid
      chromatography, HPLC) measured in the basal ganglia of the 20- to 40-min-old
      newborn and 4-week-old male rat. Asphyxia was induced in pups by placing the
      fetuses, still in their uterus horns removed by hysterectomy from pregnant rats
      at full term, in a 37 degrees C water bath for 15-16 min or 19-20 min. Following
      asphyxia, the uterus horns were opened, and the pups were removed and stimulated
      to breathe. A 100% and 50-80% pup survival was obtained following 15-16 min and
      19-20 min of asphyxia, respectively. Acute changes were studied in brains from
      newborn pups 20-40 min after delivery, and long-term changes were studied in
      brains from 4-week-old rats. No changes in TH-activity could be observed in the
      substantia nigra/ventral tegmental area (SN/VTA), the striatum, or the accumbens
      nucleus/olfactory tubercle (ACC/TUB), in the newborn or the 4-week-old rat. In
      the newborn rat, 19-20 min of asphyxia increased (as compared to controls)
      dopamine levels in the SN/VTA to 136 +/- 14% and in the ACC/TUB to 160 +/- 10%,
      indicating an increased synthesis and/or release of dopamine. DO-PAC levels were
      increased in the SN/VTA to 150 +/- 14% and in the ACC/TUB to 151 +/- 10%, and HVA
      levels were increased to 152 +/- 16% in the striatum and to 117 +/- 4% in the
      ACC/TUB. Following 15-16 min of asphyxia, dopamine levels were increased to 130
      +/- 12% in the ACC/TUB, and DOPAC levels were increased to 135 +/- 6% and 130 +/-
      12% in the SN/VTA and the ACC/TUB, respectively. This suggests that the increased
      dopamine levels may preferably reflect an increased release of dopamine following
      perinatal asphyxia. In the 4-week-old rat, dopamine levels were decreased in the
      SN/VTA to 71 +/- 4%, in the striatum to 52 +/- 8%, and in the ACC/TUB to 53 +/-
      7%, following 19-20 min of perinatal asphyxia as compared to controls. No changes
      were observed in DOPAC, HVA, or 3-MT levels, indicating that the reduced dopamine
      levels reflect a reduced dopamine synthesis following perinatal asphyxia. A
      decrease in dopamine utilization was observed in the striatum to 15 +/- 8% and in
      the ACC/TUB to 9 +/- 13% following 19-20 min of perinatal asphyxia as compared to
      controls. This indicates that perinatal asphyxia produced long-lasting reductions
      in activity in the mesostriatal/mesolimbic dopamine systems in the 4-week-old
      rat.

PMID- 9007544
TI  - Reorganization in the auditory cortex of the rat induced by intracortical
      microstimulation: a multiple single-unit study.
AB  - Many manipulations are able to change or perturb various aspects of single neuron
      properties and interneuronal relationships. Changes of cerebral cortex
      organization have been observed in different cortical areas and at different time
      scales in relation to peripheral stimulation, peripheral damage, associative
      learning, and electrical stimulation. Here we describe studies on separable
      multineuron recordings in the rat's auditory cortex under two different
      anesthetics. Acoustic stimuli were used as a normal, physiological input, and
      weak electrical intracortical microstimulation (ICMS) as a perturbation that
      forces a rapid cortical reorganization. ICMS induced fast changes in the cortical
      map and in the receptive field properties of cells at the electrically stimulated
      and adjacent electrodes. In effect there was an enlargement of the cortical
      domain tuned to the acoustic frequency that had been represented at the
      stimulating electrode. ICMS also incremented afterdischarge responses; these
      consisted of an initial response to the auditory stimulus followed by less
      intense repetitive activity that was stimulus-time locked and had a period of 8
      12 Hz, similar to that of the spontaneous synchronous activity. Cortical activity
      under ketamine differed from that under pentobarbital sodium, although in both
      situations we observed that cortical neurons were highly synchronous.

PMID- 9007545
TI  - Neuronal assembly dynamics in the rat auditory cortex during reorganization
      induced by intracortical microstimulation.
AB  - Single neurons, acting alone, cannot account for the complex and rapid
      computations that are routinely accomplished by the behaving nervous system.
      Recent studies with separable multineuron recordings are showing that neuronal
      assemblies can indeed be detected and that their organization is very dynamic,
      depending on variables such as time, physical stimulus, and context. Here we
      explore both single-neuron and assembly properties in the rat's auditory cortex.
      Acoustic stimuli are used as a normal, physiological input, and weak electrical
      intracortical microstimulation (ICMS) as a perturbation that forces a rapid
      cortical reorganization. In this setting, various aspects of neuronal
      interactions are changed by the ICMS. We found that cortical neurons exhibited
      highly synchronous oscillatory firing patterns that were enhanced by ICMS. Cross
      correlation studies between two spike trains showed that statistically
      significant correlations depended on the anatomical distance between the two
      neurons. ICMS changed the strength and the local number of such correlations.
      Joint petristimulus analysis and gravity analysis showed that the correlation
      between neuronal activities varied dynamically at several time scales. We have
      identified neuronal assemblies in two ways, defined through similarity of
      receptive field properties and defined through correlated firing. Close
      anatomical spacing between neurons was conducive to, but not sufficient for
      membership in, the same assembly with either definition. ICMS changed cortical
      organization by altering assembly membership. Our data show that neuronal
      assemblies in the rat auditory cortex can be established transiently in time and
      that their membership is dynamic.

PMID- 9007546
TI  - The perception and prehension of objects oriented in the depth plane. I. Effects
      of visual form agnosia.
AB  - Previous studies have reported that the visual form agnosic D.F. is able to use
      information about visual targets for the control of motor acts, but has great
      difficulty in using the same visual information for perceptual report. This
      intact visuomotor performance may be mediated by relatively intact parieto
      frontal cortical mechanisms. The present study investigated the ability of D.F.
      to use binocular and monocular information about the orientation of an object in
      the depth plane for perceptual and visuomotor purposes. A square plaque was
      presented at seven different orientations in depth to D.F. and to three age- and
      sex-matched control subjects. Subjects were required to reach out and grasp the
      plaque using a precision grip (index finger and thumb) under binocular and
      monocular viewing conditions, and in separate trials to match the orientation of
      a hand-held plaque to the perceived orientation of the target object, also under
      both binocular and monocular conditions. D.F.'s performance in grasping trials
      was found to be normal under binocular conditions, but was substantially worsened
      by removal of binocular vision. She was severely impaired at matching the
      orientation of the test square, although under binocular conditions her
      performance rose clearly above chance. The data suggest that the separation of
      cortical processing for visuomotor and visual perceptual purposes also applies,
      at least in part, to information about the orientation in depth of an object. The
      impaired performance under monocular viewing conditions on the visuomotor task is
      in agreement with recent physiological data and suggests that posterior parietal
      systems depend critically on binocular input for the processing of orientation in
      depth when ventral-stream information is unavailable.

PMID- 9007547
TI  - Spatial pattern of evoked synaptic excitation in the mouse neostriatum in vitro.
AB  - The spatial distribution of stimulus-evoked excitation in the mouse neostriatum
      was investigated in vitro by using voltage-sensitive dyes and an optical multi
      site recording system (laser scanning microscopy). The scanning area (880 x 830
      microns) was positioned in the center of coronal neostriatal slices and records
      were taken simultaneously from up to 20 detection sites. Stimulus-induced optical
      signals were blocked by tetrodotoxin (TTX) and disappeared following removal of
      Ca2+ from the extracellular medium. Furthermore, these responses were inhibited
      by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)
      indicating that the evoked signals reflected mainly glutamatergic synaptic
      activity. Electrical stimulation at defined positions elicited characteristic
      spatial patterns of activity within the neostriatum. Stimulation of the medial
      subcortical white matter or stimulation at the dorsomedial corner or at the
      midpoint of the scanning area evoked synaptic activity at all recording sites.
      However, the largest response amplitudes were invariably observed in the
      ventrolateral part of the scanning area. In contrast, stimulation at the
      dorsolateral, ventrolateral or at the ventromedial corner induced synaptic
      responses which remained restricted to a relatively small area in close vicinity
      to the site of stimulation. The GABAA receptor antagonist bicuculline did not
      influence the pattern of activity distribution. However, in the presence of
      bicuculline, a N-methyl-D-aspartate (NMDA) receptor-mediated delayed signal
      component was observed which again was most pronounced in the ventrolateral part
      of the scanning area. These results, obtained in an in vitro slice preparation,
      demonstrate that spatially defined afferent activation of neostriatal neuronal
      circuits leads to a characteristic pattern of activity distribution within the
      neostriatum. Thus, our data complement observations from morphological
      investigations as well as from electrophysiological studies in vivo that suggest
      a functional compartmentalization of this brain area.

PMID- 9007548
TI  - The sensory guidance of movement: a comparison of the cerebellum and basal
      ganglia.
AB  - We used positron emission tomography (PET) to compare the contribution of the
      cerebellum and basal ganglia to the sensory guidance of movement. In one
      condition the subjects used a computer mouse to draw a series of lines on a
      computer screen (DRAW). In the second condition the same lines were presented to
      the subjects, and they had to track the lines with a mouse pointer on the screen
      (COPY). In a third condition the subjects were again presented with the same
      lines, and they simply followed movements of the pointer with their eyes (EYES).
      In the fourth condition, the subjects fixated a central point, ignoring the
      sequence of presented lines (FIX). The pons and cerebellum were activated more
      during visually guided tracking than in freely generated drawing (COPY vs DRAW).
      The basal ganglia were activated equally in both DRAW and COPY. The prefrontal
      and inferior temporal cortex were activated more when subjects drew lines freely
      (DRAW) than when they copied them (COPY). We conclude that the cerebellum is
      specialized for using sensory information to correct movements, but that the
      basal ganglia are involved both in movements that are self-generated and in
      movements that are guided by external cues.

PMID- 9007550
TI  - Models of behaviors when detecting displacements of joints.
AB  - This report describes two models of human behavior when detecting displacements
      of joints that allow one to compare and integrate findings from different
      proprioception tests in a quantitative way. Results from various tests have led
      to different and often conflicting conclusions about proprioceptive behaviors and
      their underlying neural mechanisms. However, it has been impossible to compare
      data and conclusions in any meaningful way due to lack of a suitable analytical
      framework to accommodate important differences in procedures used in the various
      tests. These models can provide one such framework. The models, developed using
      data from proprioception tests reported in the literature, describe how the
      amplitude and velocity of joint excursions, and the subject bias expressed as
      false alarm rate, affect the detectability of displacements of joints. Two models
      were needed to represent observed behaviors: one based on velocity signals alone
      (the velocity model) and the other based on both velocity and positional signals
      (the displacement-velocity model). To simulate the detection-decision process
      subjects used to determine whether a joint was displaced, we adapted strategies
      from signal detection theory. The models characterized reported behaviors from
      disparate proprioception tests remarkably well, requiring only 3 degrees of
      freedom in the velocity case, and 4 in the displacement-velocity case.

PMID- 9007549
TI  - Neonatal damage to the rat's infraorbital nerve upregulates both galanin and
      neuropeptide Y in individual vibrissae-related primary afferent axons.
AB  - Previous studies in adult animals have suggested that the peptides galanin and
      neuropeptide Y (NPY) may be upregulated in the same primary afferent neurons
      after peripheral axotomy. The present study was undertaken to determine whether
      such upregulation occurred in vibrissae-related primary afferent neurons and
      their axons after damage to the infraorbital nerve [ION; the trigeminal (V)
      branch that innervates the vibrissae follicles]. Double-labelling experiments
      demonstrated that approximately 75% of axotomized V ganglion cells and the
      central arbors of vibrissae-related primary afferents expressed both galanin and
      NPY after perinatal, but not adult, nerve damage. However, additional experiments
      demonstrated that the sensitive periods for lesion-induced upregulation of the
      two peptides and the period over which they were expressed after neonatal ION
      transection differed substantially. Staining for both peptides was increased
      after ION damage on P-0 through P-14, but only galanin staining was increased in
      vibrissae-related primary afferents after lesions on P-21. Galanin expression was
      elevated in vibrissae-related primary afferents in rats killed 3, 8, and 15 days
      after neonatal ION transection, while increased NPY was observed at only the
      middle time point. The lesion-induced increases in galanin and NPY in vibrissae
      related ION primary afferents suggest that these peptides may modulate central V
      reorganization after such damage.

PMID- 9007552
TI  - Short-term plasticity in primary somatosensory cortex of the rat: rapid changes
      in magnitudes and latencies of neuronal responses following digit denervation.
AB  - Recordings were made from neurons in primary somatosensory (SmI) forepaw cortex
      of rats to study the time course of changes in responses beginning immediately
      following denervation (ligation) of a single digit. Before denervation, neuronal
      receptive fields (RFs) defined by tactile stimulation varied in size from small
      regions of one digit to larger areas covering several digits and palmar pads.
      With electrical stimulation, most neurons responded best to one (on-focus) digit
      and less to other (off-focus) digits; on-focus stimulation yielded more spikes
      per stimulus and shorter spike latencies (Lmin) than did off-focus stimulation.
      After ligation of the on-focus digit, most neurons showed increased
      responsiveness to stimulating one or several off-focus digits and palmar regions
      of the forepaw: (1) tactile stimulation showed that the RFs of all but one neuron
      expanded to include previously "ineffective" skin regions, such as digits or
      palmar pads adjoining the original RF; (2) electrical stimulation usually evoked
      stronger responses from neighboring off-focus digits and sometimes elicited novel
      responses from previously ineffective digits--seven of ten neurons showed
      increases in spikes per stimulus, which tended to approach stable values within
      60-90 min after denervation; three of ten neurons showed decreases in Lmin with
      time, but most revealed no significant changes. These results suggest that
      dynamic response properties, as well as RFs, of SmI cortical neurons can be
      modified rapidly by blocking afferent input from dominant on-focus skin regions.
      RFs expand and novel responses appear, with concomitant increases in response
      magnitude and, in some cases, decreases in response latency over time. These
      findings seem to reflect a rapid increase in synaptic efficacy of weak or
      previously ineffective inputs from cutaneous afferent nerve fibers.

PMID- 9007553
TI  - Characteristics of voluntary visual sampling of the environment for safe
      locomotion over different terrains.
AB  - The characteristics of visual sampling required for successful locomotion over
      various terrains is the focus of this work. In the first experiment we directly
      address the role of continuous visual monitoring of the environment in guiding
      locomotion by allowing the subjects to choose when and where to take a visual
      sample of the terrain and examine the effects of different terrains on
      characteristics of visual sampling. Young subjects walked over travel paths of
      varying difficulties while wearing opaque liquid crystal eyeglasses and pressed a
      hand-held switch to make the glasses transparent when they needed to sample the
      environment. Travel time and visual sampling characteristics were recorded.
      Results show that intermittent sampling (less than 50%) of the environment is
      adequate for safe locomotion, even over a novel travel path. The frequency,
      duration and timing of visual samples are dependent on terrain characteristics.
      Visual sampling of the environment is unaffected by preview restriction of the
      travel path and is increased when specific foot placement is required and there
      is a potential hazard in the travel path. In the second experiment we dissociated
      steering control and obstacle avoidance from specific foot placement and examined
      visual sampling demands prior to the initiation of the swing phase and during the
      swing phase. The results show that steering control and obstacle avoidance do
      influence the visual sampling time, which is scaled to the magnitude of change.
      Vision was used in a feedforward control mode to plan for and initiate
      appropriate changes in the swing limb trajectory: its use during the swing phase
      to provide on-line control was minimal.

PMID- 9007551
TI  - Reaching to ipsilateral or contralateral targets: within-hemisphere visuomotor
      processing cannot explain hemispatial differences in motor control.
AB  - Aiming movements made to visual targets on the same side of the body as the
      reaching hand typically show advantages as compared to aiming movements made to
      targets on the opposite side of the body midline in the contralateral visual
      field. These advantages for ipsilateral reaches include shorter reaction time,
      higher peak velocity, shorter duration and greater endpoint accuracy. It is
      commonly hypothesized that such advantages are related to the efficiency of
      intrahemispheric processing, since, for example, a left-sided target would be
      initially processed in the visual cortex of the right hemisphere and that same
      hemisphere controls the motor output to the left hand. We tested this hypothesis
      by examining the kinematics of aiming movements made by 26 right-handed subjects
      to visual targets briefly presented in either the left or the right visual field.
      In one block of trials, the subjects aimed their finger directly towards the
      target; in the other block, subjects were required to aim their movement to the
      mirror symmetrical position on the opposite side of the fixation light from the
      target. For the three kinematic measures in which hemispatial differences were
      obtained (peak velocity, duration and percentage of movement time spent in
      deceleration), the advantages were related to the side to which the motor
      response was directed and not to the side where the target was presented. In
      addition, these effects tended to be larger in the right hand than in the left,
      particularly for the percentage of the movement time spent in deceleration. The
      results are interpreted in terms of models of biomechanical constraints on
      contralateral movements, which are independent of the hemispace of target
      presentation.

PMID- 9007554
TI  - Activation of the hippocampal formation by vestibular stimulation: a functional
      magnetic resonance imaging study.
AB  - Functional MRI (f-MRI) is a non-invasive technique developed to permit functional
      mapping of the brain with a better temporal and spatial resolution than that
      offered by PET techniques. In our study, f-MRI was performed using blood
      oxygenation level dependent (BOLD) contrast imaging based on the magnetic
      properties of hemoglobin. This method relies on changes in the blood supply to
      the brain that accompany sensory stimulation or changes in cognitive state. All
      the images were obtained at 1.5 T on a Signa GEMS without ultrafast imaging. The
      vestibular stimulation was cold irrigation of the external auditory meatus
      (caloric stimulation). A population of normal healthy volunteers without a
      history of vestibular dysfunction was studied. The hippocampal formation as well
      as the retrosplenial cortex and the subiculum were activated by vestibular
      stimulation, suggesting that this activation may be related to spatial
      disorientation and a sensation of self-rotation experienced by the subjects
      during vestibular stimulation. The other results are similar to those obtained
      using PET.

PMID- 9007555
TI  - Clinical practice in academic medical center departments of family medicine. The
      Association of Departments of Family Medicine Task Force on Clinical Practice in
      US family medicine departments in academic medical centers.
AB  - BACKGROUND AND OBJECTIVES: Conducted by a task force of the Association of
      Departments of Family Medicine, this study defines current issues in the clinical
      practice of academic departments of family medicine in US medical schools.
      METHODS: A survey instrument on departmental demographics, funding, teaching, and
      governance in regard to clinical practice was sent to 130 family medicine
      department chairs or other key contacts in US medical schools. A total of 106
      usable responses were obtained, for an 81.5% response rate. RESULTS: Results
      indicate that, in response to a need to increase clinical practice income,
      academic medical centers (AMCs) and departments are increasingly hiring physician
      faculty for positions that mainly involve patient care, although at salaries less
      than the community level. In spite of increasing departmental responsibilities in
      predoctoral and resident education and clinical practice, much teaching is done
      by community physicians. There is significant purchasing of community practices
      and growing involvement of the AMCs in the practice activities of departments.
      Two thirds of clinical chairs reported "pretty good" to "great" satisfaction on a
      five-point scale. CONCLUSIONS: Departments of family medicine are increasing
      their practice activities, perhaps to the detriment of teaching and research. The
      clinical practice autonomy of departments of family medicine is being diluted by
      increased institutional control and by mergers with the practices of other
      primary care disciplines. These changes give rise to a reasonable concern that
      academic departments of family medicine and their faculty may give up control of
      their clinical practice and lose their identity through conversion to "generic"
      primary care departments and providers.

PMID- 9007556
TI  - Skills actively performed during a family medicine community-based preceptorship.
AB  - BACKGROUND: This study assessed the clinical learning experiences provided to
      third-year medical students during a 2-week, required, community-based family
      medicine preceptorship. METHODS: After completing the preceptorship, students
      classified their level of performance on 80 clinical activities. During 3
      academic years, 486 third-year students completed the preceptorship. RESULTS:
      Delivery of well-child care was the only prevention skill in which a high
      percentage of students (more than 67%) received experience; students received
      moderate experience (34%-67% of students) with another seven prevention skills.
      Students received a high level of active experience with four clinical problems-
      upper respiratory tract infection, acute otitis media, sinusitis, and strep
      throat--and a moderate level of active experience on another 17 clinical
      problems. There were no procedural skills on which students received a high level
      of experience, but students received a moderate level of experience with 10
      procedural skills. CONCLUSIONS: This brief family medicine preceptorship provided
      a clinical setting in which students actively engaged in several facets of
      ambulatory primary care. For accountability, programs need to more clearly
      articulate what exposure is to be gained in each clinical rotation, strive to
      enhance active practice, and document levels of student performance.

PMID- 9007557
TI  - Using standardized patients in licensing/certification examinations: comparison
      of two tests in Canada.
AB  - BACKGROUND: A new licensing examination for family physicians was introduced in
      the Province of Quebec, Canada, in 1990. It contains a newly developed,
      standardized, patient-based objective structured clinical examination (OSCE) used
      in complementarity with two other instruments (Short Answers Management Problems
      [SAMPs] and Simulated Office Orals [SOOs]) that have been used for many years by
      the College of Family Physicians of Canada (CFPC) for certification purposes.
      This research studied the criterion validity of the OSCE using the last
      instruments as criteria. METHODS: The results of the 172 spring 1994 candidates
      were analyzed. Cronbach alpha reliability coefficients were computed. Pearson's
      correlation coefficients and regression analysis measured the extent to which
      scores on the new Quebec OSCE correlated with the scores on the CFPC instruments.
      RESULTS: Correlation coefficients were significant between the Quebec OSCE scores
      and the CFPC examination total scores (.700), the SAMPs scores (.634), and the
      SOOs scores (.514). Multiple regression analysis confirmed that scores on the
      Quebec OSCE explained a significant but still limited proportion of the variation
      in scores of the CFPC examination. DISCUSSION: This study supports the criterion
      validity of the Quebec OSCE used in the licensing examination. However,
      differences in the skills assessed by each instrument and in the clinical
      situations presented exist between the Quebec instrument and the two national
      instruments. These differences, plus the variation in the scores obtained by the
      candidates on the three instruments, support the decision of the Quebec licensing
      organization to use them in complementarity.

PMID- 9007558
TI  - Family practice residency program directors' views on research.
AB  - BACKGROUND AND OBJECTIVES: The culture of family practice training programs does
      little to convince residents that research is a worthwhile and important
      activity. The traditional dichotomy between research and clinical medicine
      persists today, despite an identified clinical mission for research. METHODS: As
      part of an effort to build the research capacity of family practice training
      programs, a telephone survey was administered in August 1995 to the program
      directors of all residency programs listed in the American Academy of Family
      Physicians 1995 Directory of Family Practice Residency Programs. The directors
      were asked about their program's research environment, features designed to
      promote research activity, and the level of resident research productivity.
      RESULTS: More than half (53.6%) of the program directors felt that their training
      program actively promotes research. Three out of four indicated that involving
      residents in research is a goal of their program. However, only four of 10
      (40.8%) programs provide specific time for research, and family practice
      residents appear to be relatively inactive by conventional measures of research
      productivity. CONCLUSIONS: Research appears to be developing a limited role in
      family practice training programs. Resident research productivity remains
      relatively low and may be a result of residency programs not providing specific
      time for participating in research. However, the program directors' supportive
      attitudes may contribute to research and scholarly activity becoming an integral
      part of a family physician's training.

PMID- 9007559
TI  - Evidence-based management of upper respiratory infection in a family practice
      teaching clinic.
AB  - BACKGROUND AND OBJECTIVES: Management of upper respiratory infection (URI) was
      examined in a family practice clinic to determine evidence-based practices,
      specifically for medication choice. Scientific evidence supports the use of
      decongestants and perhaps decongestant/antihistamine combinations in adolescents
      and adults and antipyretics in all age groups. The use of cold preparations for
      children younger than age 5 is not evidence based. METHODS: Data on demographics,
      medications prescribed, and over-the-counter medications recommended were
      collected from patient charts for 293 URI visits over a 6-month period. The cost
      of evidence-based URI treatment was compared with the cost of nonevidence-based
      treatment. RESULTS: Thirty-three percent of patients younger than age 5 were
      given a prescription; 96% of the prescription cost in this age group was
      nonevidence based. Twenty-six percent of all patients seen were given unnecessary
      and potentially harmful medication. These unnecessary medications accounted for
      almost 60% of the total prescription cost. Various combinations of
      antihistamines, decongestants, and antitussives were most commonly prescribed.
      CONCLUSIONS: Few medications have been shown to effectively alleviate the
      symptoms of the generally self-limited, benign common cold. Medications are often
      overprescribed, escalating health care costs and, in some cases, exposing the
      patient to dangerous side effects. Family physicians and educators are encouraged
      to reexamine their treatment and teaching practices for the common cold.

PMID- 9007560
TI  - A method for assigning authorship in multiauthored publications.
AB  - BACKGROUND AND OBJECTIVES: Determining authorship for publications is often a
      difficult process, even more so when individuals from several disciplines
      collaborate with community organizations to conduct projects. Although
      multidisciplinary and community-academic partnerships provide fertile ground for
      publication efforts, disputes about authorship and ownership of data may hinder
      efforts to disseminate information. This article describes a process for dealing
      with authorship in multi-professional collaborations. It provides an authorship
      scale, similar to a neonatal Apgar scale, to determine order of authorship in
      multi-professional projects. Key components or activities in the process of
      authorship are identified, and points are assigned to each component in
      proportion to an investigator's level of activity in each component/activity.
      Scores are summed and can range from 1 to 35 for each author. The order of
      authorship is then determined by the relative score of each participant.

PMID- 9007562
TI  - Family medicine in four dimensions: developing an ecobiopsychosocial perspective.

PMID- 9007561
TI  - Collegial networking and faculty vitality.
AB  - BACKGROUND: This research explored the relationship between collegial networking
      and faculty "vitality" among graduates of the family medicine faculty development
      fellowship at the University of North Carolina at Chapel Hill. Faculty vitality
      was defined by retention in full-time teaching, job satisfaction, academic
      activity, and contributions to the discipline. METHODS: A questionnaire was
      mailed to 170 family physician graduates of the 1980-1992 fellowship classes.
      After a mail and telephone follow-up, the response rate was 85%. Data were
      collected on career history, professional interests, professional relationships,
      assessment of fellowship, and professional activities. RESULTS: Respondents with
      collegial networks were more likely to participate in several academic activities
      and were more likely to remain in full-time teaching. No association was found
      between collegial networks and satisfaction or contributions to the discipline.
      There were only small differences in effect between intra-departmental and extra
      departmental collegial networks. Stratification by program type and gender
      revealed no evidence of effect modification or confounding. CONCLUSIONS:
      Collegial networks influence some aspects of faculty vitality, particularly
      retention in full-time teaching. Further research is needed to fully understand
      its impact.

PMID- 9007563
TI  - Bayesian estimation of the parameters of a nonlinear model. An application to
      human height.
AB  - The estimation of the parameters of a nonlinear model by means of the maximum
      likelihood procedure is widely used in the study of growth phenomena. The
      accuracy with which these parameters are calculated is a function of the number
      of measures taken and particularly, of their distribution across the growth
      period. If the growth curve is only partially known, the inaccuracy can increase
      considerably. However, if we have information on the distribution of the
      parameters of a model in the population, the empirical Bayes method should be
      used. In this paper, the principle of this approach for nonlinear modeling was
      recalled. The method was then applied on data of human height. Four nonlinear
      models are used and their performances are compared. The results show the
      importance of information on the quality of estimates of growth parameters and
      consequently on the prediction of adult height.

PMID- 9007564
TI  - Effects of exposure to polychlorinated biphenyl (PCB) from conception on growth,
      and development of endocrine, neurochemical, and cognitive measures in 60 day old
      rats.
AB  - Industrially employed PCB has caused wide-spread environmental contamination
      through improper disposal and has been associated with detrimental physiological
      states in exposed organisms, including depressed body weight, food consumption,
      and circulating levels of T4 and T3. Previously, the activity of choline
      acetyltransferase (ChAT) in the basal forebrain and hippocampus was shown to be
      depressed in young rats exposed to the PCB diet from the time of conception. The
      present study measured the neurochemical effects of similar PCB exposure in older
      (i.e., 60 day old) rats, and examined possible restoration of PCB-induced
      deficits by removing PCB at weaning (28 days). Possible PCB-induced impairment of
      memory was also evaluated with a radial arm maze. Findings included a significant
      depression of circulating levels of T4 in all treatment groups with the most
      profound depression seen in rats continuously fed PCB. Also, T3 levels and
      relative thyroid weights were not found to be severely depressed. The ChAT
      activity in both the basal forebrain and hippocampus was not different from
      control in all treatment groups. It appears that the effect of PCB on thyroxine
      is persistent, but its influence on ChAT activity is not. However, modest memory
      deficits were observed despite normal ChAT activity. Average number of working
      memory errors per test session in the maze increased in a dose-dependent manner
      across treatment groups.

PMID- 9007565
TI  - Transient postweaning expression of excessive fat deposition and diabetes
      mellitus in ob/ob mice.
AB  - Growth, glucose levels and body composition of male and female C57BL/6 ob/ob and
      lean (?/+) mice were examined between 17 days and 1 year of age. Obese mice
      displayed three distinct periods of growth with each phase characterized by a
      different pattern of glucoregulation. Until 4 weeks of age, ob/ob mice had
      slightly higher rates of weight gain and fat accretion than littermate lean mice.
      Glycemia was in the normal range and insulin levels were elevated. Shortly after
      the transition to solid food, ob/ob mice displayed several weeks of increased
      body growth and very high rates of fat deposition. During this period of rapid
      weight gain, hyperglycemia arose despite progressively increasing IRI
      concentrations. Examination of individual obese mice at this time revealed that
      glycemia was highly correlated with the rate of body fat deposition. The final
      phase of the ob/ob syndrome began at 3 months of age, as rates of fat deposition
      abruptly slowed to values slightly less than those of lean mice and glucose
      values declined to normal although hyperinsulinemia and glucose intolerance
      persisted. The present results show that ob/ob mice, although characterized
      throughout life by many metabolic and growth disturbances, only display diabetes
      mellitus and exaggerated fat deposition during a 6 to 8 week period just after
      weaning.

PMID- 9007566
TI  - Changes in alveolar capillary formation in growing rat lung by repeated
      injections of a lathyrogen.
AB  - We hypothesized that abnormal capillary formation, which might be associated with
      an alteration in extracellular malular matrix (ECM), occurs in the alveoli of
      growing rat lungs treated with beta-aminopropionitrile (beta APN), a lathyrogen
      that inhibits lysyl oxidase activity. On scanning electron microscopy, a
      corrosion cast of alveolar capillaries in lungs treated with beta APN appeared
      abnormal in configuration; transmission electron microscopy showed extensive
      morphological changes in interstitial cells and ECMs, including collagen,
      elastin, and presumably glycosaminoglycans and, in binding water (GBW).
      Morphometric data revealed an increase in GBW of up to 24.4%, a decrease in the
      amount of collagen fiber (44.5%), and a decrease in lipid-laden interstitial
      cells; however, the change in elastin was limited to morphological appearance.
      From these observations, we conclude that alterations in alveolar capillary
      formation are associate with extensive changes in ECMs, and that these changes in
      ECM components might also be involved in the abnormal alveolar formations induced
      by beta APN.

PMID- 9007567
TI  - The effect of methimazole on the growth of the developing brushtail possum,
      Trichosurus vulpecula.
AB  - The brushtail possum, Trichosurus vulpecula, produces a single offspring 200 mg
      in body weight. The young grow slowly during the first half of pouch of life at
      approximately 1g/day. At day 96 post partum the growth rate increases
      dramatically and it has been suggested that this change in growth rate may result
      from the initiation of thyroid function in the young possum. To determine the
      role of the thyroid gland of the possum on growth, the production of hormones
      from the thyroid was inhibited by administration of the drug, methimazole. The
      drug was administered to adult and young possums at day 140 post partum for 28
      days and to young at day 100 post partum for 42 days and the effects of this
      treatment on plasma concentrations of thyroxine and on growth were monitored.
      Methimazole was found to inhibit thyroxine production in 4 of the 6 adult possums
      although it had no effect on body weight. Similar treatment administered to nine
      young possums inhibited growth. The three surviving methimazole possum young
      treated at 100 days post partum weighed less than control possums after day 163
      post partum. The four young treated at 140 days post partum also showed
      depression in growth rate. However, the depression was not as marked as that of
      the 100 day treated possums. It is highly likely therefore that the surge in
      growth rate in the possum at day 96 post partum is initiated by thyroxine
      produced by the thyroid gland of the young.

PMID- 9007568
TI  - Ontogeny of IGFs and IGFBPs mRNA levels and tissue concentrations in liver,
      kidney and skeletal muscle of pig.
AB  - As far as we know, there is no available information about ontogenic changes of
      tissue concentrations of IGF-I and II and IGFBPs in large mammals. Serum, liver
      and kidney levels of IGFs and IGFBPs were examined in fetuses at 90 and 110 days
      of gestation and in pigs at 1d, 3 wk, 3 mo and 6 mo of age. Ontogeny of mRNA
      levels of IGFs, IGF type I and type II receptors (IGFI-R and IGFII-R), IGFBP-1
      and -3 (IGFBPs) and growth hormone receptor (GHR) were also examined by Northern
      blot analysis in liver, kidney and skeletal muscle of pig. Serum IGF-I, IGF-II
      and IGFBP-3 concentrations were low during the fetal life and increased after
      birth. The highest level of IGF-II mRNA was found in fetuses for all studied
      tissues. In the liver, IGF-I mRNA level and its protein content peaked at 3 wk of
      age. The highest IGF-II concentration was found at 1d and 3 wk of age. The IGFII
      R mRNA remained at a constant level during the whole development period. The most
      abundant IGFBP-1 mRNA and its protein content were found at birth. The level of
      IGFBP-2 was high during fetal and early postnatal life. The IGFBP-3 content was
      relatively low in fetuses and reached the highest level after 3 wk of age. In the
      kidney, IGFs, IGFBP-3, IGFI-R and IGFII-R as well as GHR mRNA levels were
      relatively high during the fetal and early postnatal life. The IGFs
      concentrations were the highest in newborns. In the skeletal muscle, IGFs, IGFBP
      3 and IGFI-R mRNA levels decreased with advancing age. During the postnatal life,
      the high IGFs concentrations in the liver and the kidney correspond to fast
      growth periods of these organs.

PMID- 9007569
TI  - Excitatory and inhibitory response adaptation in the superior olive complex
      affects binaural acoustic processing.
AB  - Short-term adaptation was examined in single unit recordings from 113 superior
      olive neurons of anaesthetized 3- to 6-month-old Long-Evans rats. Responses to an
      equal intensity BF probe tone presented 1 ms after an 'adapting' BF tone were
      adapted by 56.3 +/- 2.6% (mean +/- S.E.) compared to responses at a 512 ms delay.
      The rapid decrease in discharge rate during adapting tones often approximated
      exponential time courses with time constants of less than 20 ms. The recovery
      from adaptation was exponential with time constants of 106 +/- 20.0 ms. The
      magnitude of adaptation and time course of recovery following monaural
      stimulation of binaurally excited (EE) neurons were not significantly different
      in both input pathways. Additionally, in 60% of EE neurons, an 'adapting' tone
      presented to one ear reduced subsequent responses to probe tones presented to the
      opposite ear. Binaural stimulation resulted in equal or greater adaptation of
      responses than monaural stimulation of either ear. The recovery of binaural
      excitatory responses generally followed a time course between recovery functions
      for ipsilateral and contralateral monaural stimuli. Lateral Superior Olive (LSO)
      neurons encode sound source location through the interaction of ipsilateral
      excitation and contralateral inhibition (IE). Ipsilaterally driven excitatory
      responses in LSO neurons exhibited the greatest magnitude of adaptation (68.5 +/-
      21.1%). Adaptation of inhibition was observed in over half of IE neurons.
      Responses of LSO neurons to binaural BF probe stimuli were greatest immediately
      after a 200 ms BF 'inhibitory adapting' stimulus to the contralateral ear, and
      decreased with greater interstimulus delays. Responses to binaural stimulation
      were constant after prior binaural adaptation, when the magnitude and recovery of
      adaptation to monaural stimuli were similar for excitation and inhibition (8/25
      IE cells). The functional significance and possible sites of adaptation processes
      are discussed.

PMID- 9007570
TI  - Interaction of otoacoustic emissions with additional tones: suppression or
      synchronization?
AB  - The influence of an external tone on transitory evoked otoacoustic emissions
      (TEOAE) is investigated. Three different averaging techniques were used with the
      same acoustic stimulus paradigm. These techniques permitted the separation of
      those parts of the otoacoustic emission (OAE) that contribute to the transitory
      evoked otoacoustic emission and those parts of the OAE that are synchronized to
      the continuous tone. The experiments show that the total energy of the OAE is not
      reduced in the presence of an additional tone. The 'suppression' of TEOAEs is an
      effect of synchronization and the subsequent elimination of the 'suppressed'
      emission in the averaging procedure.

PMID- 9007571
TI  - Prevalence of spontaneous otoacoustic emissions in adults revisited.
AB  - The potential influence of spectral analysis factors on estimates of the
      prevalence of spontaneous otoacoustic emissions (SOAE) was explored. The
      detection of a SOAE was influenced by two spectral factors: (1) the frequency
      resolution of the spectrum, and (2) the number of spectral averages. For 15
      different combinations of these two factors, the estimate of the prevalence of
      SOAEs for females ranged from 64 to 81% and, for males, from 39 to 55%. Combining
      across all 15 combinations, 83% of the females and 62% of the males were judged
      to have SOAEs. These results provide a context for understanding the
      inconsistencies in previous estimates of the prevalence of SOAEs and underscore
      the need to employ many different spectral analyses because some SOAEs are only
      detected when the spectral analyses are suitably tailored.

PMID- 9007572
TI  - Human offset auditory brainstem response: effects of stimulus acoustic ringing
      and rise-fall time.
AB  - Offset auditory brainstem response (ABR) traditionally has been thought to be an
      artifactual response elicited by stimulus acoustic ringing. Additionally, offset
      ABR's sensitivity to stimulus rise-fall time has been associated with concurrent
      changes in acoustic ringing. The present study tested the validity of offset ABR
      by recording the response in 40 young, normal-hearing adults using tone burst
      stimuli with varying degrees of acoustic ringing and various rise-fall times.
      Stimuli were computer-generated 10-ms tone bursts of 500 and 2000 Hz. In
      Experiment 1, offset ABR was recorded using stimuli with no acoustic ringing,
      normal ringing, and excessive ringing. Rise-fall time was held constant at 0.5
      ms. In Experiment 2, rise-fall time was manipulated in a stimulus with no
      ringing. In Experiment 3, only rise time was manipulated in a no-ringing
      stimulus, while fall time was held constant at 0.5 ms. Reliable offset ABRs were
      recorded for all degrees of acoustic ringing, including the "no-ringing'
      condition. Offset ABR was sensitive to rise and fall times, and was elicited best
      with a 500-Hz stimulus. The results indicate that offset ABR is a real response
      and not an artifact produced by acoustic ringing.

PMID- 9007573
TI  - Stria vascularis morphogenesis in vitro.
AB  - Explants of neonatal murine stria vascularis were maintained in vitro to evaluate
      the process of morphogenesis in cochlear tissue. Immunohistochemical and electron
      microscopic studies showed that the relatively undifferentiated cells in culture
      attained morphological features characteristic of the stria vascularis cell types
      in vivo (marginal, intermediate and basal cells). The three kinds of cells formed
      a trilaminated tissue, with the epithelial cells bordering the culture medium,
      basal-like cells resting on the culture substrate, and the melanocytes layered
      between. Furthermore, approximately 20% of these cultures displayed a unique
      alignment of melanocytes which formed elongated bands along the contour of the
      tissue edge. However, only limited cell extensions were formed between different
      cell types and interdigitation amongst these processes was abbreviated. Thus,
      cells from different embryological origins divided, migrated and reestablished
      appropriate cell-to-cell associations to form a layered tissue similar to the
      stria vascularis in vivo.

PMID- 9007574
TI  - Expression of voltage-dependent chloride channels in the rat cochlea.
AB  - Voltage-dependent chloride (ClC) channels have not yet been identified in the
      cochlea. In this study, an approach utilizing the reverse transcription
      polymerase chain reaction (RT-PCR) was devised to clone the cDNA of ClC channels.
      PCR was performed using degenerate primers corresponding to two highly conserved
      regions of the ClC channels. By Southern hybridization and sequencing studies,
      the sequences corresponding to ClC-2 and ClC-3 were found in the cochlear lateral
      wall, while ClC-1 was not detected. These results suggest that ClC-2 and ClC-3
      might be involved in Cl- transport in the cochlear lateral wall.

PMID- 9007575
TI  - Turner's syndrome and hearing disorders in women aged 16-34.
AB  - Forty women with Turner's syndrome aged 16-34 years were tested clinically and
      audiometrically according to their ear problems and hearing. A high incidence of
      middle-ear infections was demonstrated. A mid-frequency sensorineural hearing
      loss was frequently diagnosed and could be correlated to the karyotype. The dip
      showed a progression with age. Middle-ear problems were more common among women
      with a dip. An early high-frequency hearing loss could be noted in the present
      group among the older women. In some cases this had already led to social hearing
      problems and use of hearing aids. When comparing these women with a group of
      elderly Turner women the dip was not as deep, the maximum peak was seen in the 2
      kHz region and social hearing problems and hearing aids were not as frequent. If
      no dip was found no major hearing problems could be detected or expected in
      future life. The data emphasize the importance of early audiological evaluation
      and information about predisposition to hearing impairment in Turner's syndrome.

PMID- 9007576
TI  - The number of primary auditory afferents in the rat.
AB  - Published estimates of the number of primary auditory afferents in the rat differ
      by as much as 30%. We undertook to determine if the widely varying estimates were
      related to methodological differences, especially the difference between counting
      cells in Rosenthal's canal and fibers in the cochlear nerve. Type I ganglion
      cells and myelinated cochlear nerve fibers in the same ears were counted in Long
      Evans and Sprague-Dawley strains. Type II spiral ganglion cells were also
      counted. In each strain the numbers of myelinated fibers and type I ganglion
      cells were essentially the same. Means for the Long-Evans were 18,036 fibers and
      17,749 cells. Means for Sprague-Dawleys were higher: 19,444 fibers and 19,229
      cells. The mean number of type II ganglion cells was also greater in Sprague
      Dawley than in Long-Evans rats: 1,388 and 1,170, respectively. Cell and fiber
      counts from the two ears of the same animal differed on average by only 1%. The
      number of auditory afferents did not change with age over the range (2-10 months)
      studied here. Several methodological differences have probably contributed to the
      varying estimates of type I primary auditory afferents, but the discrepancies are
      not inherent in counts of fibers and spiral ganglion cells.

PMID- 9007577
TI  - Intracellular distributions and putative functions of calcium-binding proteins in
      the bullfrog vestibular otolith organs.
AB  - Hair cells in the bullfrog vestibular otolith organs were immunolabeled by
      monoclonal and polyclonal antisera against calbindin (CaB), calmodulin (CaM),
      calretinin (CaR), and parvalbumin (PA). S-100, previously shown to immunolabel
      striolar hair cells in fish vestibular organs, only weakly immunolabeled hair
      cells in the bullfrog vestibular otolith organs. Immunolabeling was not detected
      in supporting cells. With the exception of CaR, myelinated axons and unmyelinated
      nerve terminals were immunolabeled by all of the above antisera. Immunolabeling
      was seen in all saccular hair cells, although hair cells at the macular margins
      were immunolabeled more intensely for CaB, CaM, and PA than more centrally
      located hair cells. As the macula margins are known to be a growth zone, this
      labeling pattern suggests that marginal hair cells up-regulate their calcium
      binding proteins during hair cell development. In the utriculus, immunolabeling
      for CaM and PA was generally restricted to striolar hair cells. CaR
      immunolabeling was restricted to the stereociliary array. Immunolabeling for
      other calcium-binding proteins was generally seen in both the cell body and hair
      bundles of hair cells, although this labeling was often localized to the
      stereociliary array and the apical portion of the cell body. CaM and PA
      immunolabeling in the stereociliary array in saccular and utricular striolar
      cells suggests a functional role for these proteins in mechanoelectric
      transduction and adaptation.

PMID- 9007578
TI  - On the role of the olivocochlear bundle in hearing: 16 case studies.
AB  - Earlier we presented data (Scharf et al. (1994) Hear. Res. 75, 11-26) from a
      young patient (S.B.) who had undergone a vestibular neurotomy, during which the
      olivocochlear bundle (OCB) was severed. Those data are complemented by
      measurements on 15 other patients-some like S.B. with normal audiometric
      thresholds, none with a loss greater than 35 dB at experimental frequencies.
      Comparisons of performance for the same ear before and after surgery or between
      the operated and healthy ears do not provide evidence that the lack of OCB input
      impairs the following psychoacoustical functions: (1) detection of tonal signals,
      (2) intensity discrimination, (3) frequency selectivity, (4) loudness adaptation,
      (5) frequency discrimination within a tonal series, (6) in-head lateralization.
      Data on single-tone frequency discrimination are equivocal. These mostly negative
      results apply to listening both in the quiet and, where relevant, in noise. The
      only clear change in hearing after a vestibular neurotomy is that most patients
      detect signals at unexpected frequencies better than before. This change suggests
      an impaired ability to focus attention in the frequency domain. Although limited
      in scope, our finding that human hearing without OCB input is essentially normal
      agrees with much of the relevant literature on animal behavior and with the
      patients' self-reports.

PMID- 9007579
TI  - Expression of highly polysialylated NCAM (NCAM-H) in developing and adult chicken
      auditory organ.
AB  - Neural cell adhesion molecule (NCAM) is highly polysialylated (NCAM-H) in
      developing tissues, and recent findings suggest that NCAM-H is more essential for
      neural development than poorly sialylated NCAM (NCAM-L). In order to understand
      the precise role of NCAM-H in developing and adult inner ears, the
      immunohistochemical localization of NCAM-H in developing and adult chicken inner
      ears was examined using a monoclonal antibody which is only specific for NCAM-H.
      Immunoreactivity of NCAM-H was initially observed on acoustic ganglion at stage
      24, when peripheral (afferent) fibers begin to emerge from the ganglion cells. At
      stage 38, when peripheral fibers form synapses with hair cells, NCAM-H was
      observed on peripheral fibers and the base of hair cells in the auditory
      epithelium. At stage 42, NCAM-H on nerve fibers disappeared, and only some
      acoustic ganglion cells were still positive for NCAM-H. This immunostain on
      ganglion cells was retained after birth. These data are consistent with the
      hypothesis that NCAM-H specifically regulates the afferent nerve fibers' growth
      and synaptogenesis with hair cells during inner ear development and may be
      associated with processing of auditory information and neuronal plasticity.

PMID- 9007581
TI  - Low-frequency 'conditioning' provides long-term protection from noise-induced
      threshold shifts in chinchillas.
AB  - Studies have shown that loss of auditory sensitivity caused by exposure to high
      level acoustic stimuli can be significantly reduced by pre-exposing the subject
      to moderate-level acoustic stimuli. Although the protective effects of such
      'conditioning' exposures have been well documented, very little is known about
      the persistence of conditioning-induced protection, or about the biological
      mechanisms underlying it. In the present study, the persistence of conditioning
      induced protection was examined in chinchillas by imposing either a 30- or 60-day
      recovery period between conditioning (10 days of exposure to 0.5 kHz noise at 90
      or 95 dB, 6 h/day) and high-level (0.5 kHz noise at 106 dB for 48 h) exposures.
      Comparisons of threshold shifts between conditioned animals and control animals
      exposed only to high-level noise indicated that conditioning provided significant
      protection from noise-induced threshold shifts for at least 2 months. Conditioned
      animals sustained outer hair cell losses similar to controls, ranging from 15 to
      30% in the apical half of the cochlea. The results suggest that low-frequency
      conditioning can trigger long-lasting changes in cochlear homeostasis rather than
      temporary changes in physiology or reductions in susceptibility to hair cell loss
      in chinchillas.

PMID- 9007580
TI  - Antibodies to the sulphated, high molecular mass mouse tectorin stain hair
      bundles and the olfactory mucus layer.
AB  - Polyclonal antibodies were raised in chickens to the glycosylated forms of the
      high (H), medium (M) and low (L) molecular mass (MM) mouse tectorins. In the
      mouse cochlea, all three antibodies stained the tectorial membrane. Antibodies
      raised to HMM tectorin also stained the hair bundles of both inner and outer hair
      cells. A number of other mouse tissues were screened with the anti-tectorin
      antibodies to look for similar or antigenically related molecules. Staining was
      not observed in any other tissue type with the antibodies directed against the
      MMM and LMM tectorins. In the nose, the anti-HMM tectorin antibodies stained
      Bowman's glands and the mucus layer overlying the olfactory epithelium. The
      surface of the adjacent respiratory epithelium was not stained by these
      antibodies. HMM tectorin can be specifically radiolabelled by injecting neonatal
      mice with 35SO4 and undergoes a shift in electrophoretic mobility following
      treatment with keratanase, an endo-beta-galactosidase from Pseudomonas. However,
      when centrifuged on shallow CsCl gradients HMM tectorin has a buoyant density
      similar to that of glycoproteins and does not behave as a typical cartilage type
      proteoglycan. HMM tectorin does not react with mab 5D4, a monoclonal antibody
      that recognises keratan sulphate glycosaminoglycan from corneal and skeletal
      muscle proteoglycan. Unlike antibodies to HMM tectorin, mab 5D4 selectively
      stains the upper surface of the tectorial membrane, Hensen's stripe and the mucus
      layer overlying the respiratory epithelium. These studies indicate that the MMM
      and LMM tectorins may be unique to the cochlea, and that HMM may be a "light'
      keratan sulphate proteoglycan that is antigenically related to either the mucins
      or a more specific component of the olfactory mucus layer.

PMID- 9007582
TI  - Neuronal and transneuronal degeneration of auditory axons in the brainstem after
      cochlear lesions in the chinchilla: cochleotopic and non-cochleotopic patterns.
AB  - Terminal axonal degeneration in the brain following cochlear lesions was studied
      with the Nauta-Rasmussen method. Losses of hair cells and myelinated cochlear
      fibers were assessed. The cochleotopic map projected, from apex to base, on the
      ventral-to-dorsal axes of the cochlear nuclei. The cochleotopic correspondence
      was better for loss of cochlear nerve fibers and inner hair cells, than for outer
      hair cells. Cochlear fibers were traced to all parts of the cochlear nucleus,
      including the small-cell shell, also to cell-group Y and the flocculus. Terminal
      axonal degeneration in nuclei of the superior olivary complex, lateral lemniscus,
      and inferior colliculus was interpreted as transynaptic, since degenerated axons
      could not be traced to these locations from the cochlear nerve or trapezoid body.
      Moreover, biotinylated dextran amine injection in the basal turn of scala media
      of a normal cochlea labeled cochlear nerve fibers projecting to the high
      frequency regions of the cochlear nuclei and to the flocculus, but not to more
      central auditory nuclei. This is the first detailed account of transynaptic
      degeneration in the ascending auditory pathway resulting from cochlear damage in
      an adult mammal. These findings are consistent with a dystrophic process
      depending on hair-cell loss and/or direct damage to cochlear nerve fibers.

PMID- 9007583
TI  - Degeneration of axons in the brainstem of the chinchilla after auditory
      overstimulation.
AB  - The patterns of axonal degeneration following acoustic overstimulation of the
      cochlea were traced in the brainstem of adult chinchillas. The Nauta-Rasmussen
      method for axonal degeneration was used following survivals of 1-32 days after a
      105 min exposure to an octave-band noise with a center frequency of 4 kHz and a
      sound pressure level of 108 dB. Hair-cell and myelinated nerve-fiber loss were
      assessed in the cochlea. The cochleotopic pattern of terminal degeneration in the
      ventral cochlear nucleus correlated with the sites of myelinated fiber and inner
      hair-cell loss: this correlation was less rigorous with outer-hair-cell loss,
      especially in the dorsal cochlear nucleus. These results are consistent with a
      dystrophic process with a slow time course depending on hair-cell loss and/or
      direct cochlear nerve-fiber damage. However, in a number of cases with no damage
      in the apical cochlea, fine fiber degeneration occurred with a faster course in
      low-frequency regions in the dorsal cochlear nucleus and, transynaptically, in a
      non-cochleotopic pattern in the superior olive and inferior colliculus. These
      findings suggest that neuronal hyperactivity plays a role in the central
      degeneration following acoustic overstimulation, possibly by an excitotoxic
      process.

PMID- 9007584
TI  - Effects of lidocaine on salicylate-induced discharge of neurons in the inferior
      colliculus of the guinea pig.
AB  - Using the extracellular recording method, the effects of lidocaine (a local
      anesthetic known to relieve tinnitus) on discharge of inferior colliculus (IC)
      neurons of the guinea pig were studied before and after salicylate (200 mg/kg)
      administration. The salicylate-induced discharge was inhibited by intravenous
      injection of lidocaine at a concentration (1 mg/kg) clinically used for treating
      tinnitus. IC neurons could be classified into two groups according to the
      difference in sensitivity to lidocaine: (1) weakly-sensitive neurons and (2)
      highly-sensitive neurons. In weakly-sensitive neurons, the duration of the
      lidocaine effect lasted for less than 5 min, and the inhibitory action on the
      discharge of neurons was greater when the latency to sound stimulus became
      longer. In highly-sensitive neurons, on the other hand, the activity of neurons
      was almost completely inhibited for longer than 30 min, irrespective of the
      latency to sound stimulus. The clinical relevance of these types of neurons is
      discussed.

PMID- 9007585
TI  - The Mel Scale's disqualifying bias and a consistency of pitch-difference
      equisections in 1956 with equal cochlear distances and equal frequency ratios.
AB  - In 1956, Stevens 'commissioned' an experiment to equisect a pitch difference
      between two tones. Results appear to reveal a methodological flaw that would
      invalidate the Mel Scale (Stevens and Volkmann, 1940). Stevens sought to
      distinguish sensory continua, e.g., loudness and pitch, on various criteria. He
      expected that the pitch continuum would not exhibit 'hysteresis'; i.e., that
      subjects dividing a pitch difference (delta f) into equal-appearing parts would
      not set dividing frequencies higher when listening to notes in ascending order
      than in descending order. Seven subjects equisected a pitch difference, between
      tones of 400 and 7000 Hz, into equal-seeming parts by adjusting the frequencies
      of three intermediate tones. All seven exhibited hysteresis, contrary to
      expectation. This outcome bears on other issues. Years prior, Stevens suggested
      that equal pitch differences might correspond to equal cochlear distances, but
      not to equal frequency ratios nor to equal musical intervals (Stevens and Davis,
      1938; Stevens and Volkmann, 1940). In 1960 (reported now), both the 1940 Mel
      Scale and the equal pitch differences of 1956 were compared to equal cochlear
      distances, using a frequency-position function that fitted Bekesy's cochlear map
      (Greenwood, 1961, 1990). When ascending and descending settings were combined to
      contra-pose biases, equal pitch differences did coincide with equal distances-
      which the Mel Scale did not. Further, the biased ascending-order data coincided
      with the Mel Scale, suggesting the Mel Scale was similarly biased. Thus, the
      combined-order equal pitch differences of 1956--but not the Mel Scale--are
      consistent with equal cochlear distances. However, since the map between 400 and
      7000 Hz is nearly logarithmic, equal frequency ratios also approximate equal
      distances. Ironically, above 400 Hz, Bekesy's map and Stevens' equal-distance
      hypothesis jointly imply that musical intervals will nearly agree with equal
      pitch differences, which Stevens thought he had disconfirmed. However, given
      Bekesy's map, only near the cochlear apex will equal distances not approximate
      equal frequency ratios; and Pratt's (Pratt, 1928) bisections of delta fs greater
      than an octave indicated that equal pitch differences, on average, did agree with
      equal distances. However, they did so for only two of four subjects and coincided
      instead with equal frequency ratios for one musical subject. Historical
      distinctions suggest that between the parts of equisected delta fs subjective
      equivalence may be of two kinds--one linked to musical intervals, leading to
      equal frequency ratios; a second linked to 'tone-height' and 'distance', leading
      to deviations from equal frequency ratios near the apex, though not appreciably
      if equisected delta fs are less than an octave (or if perhaps subjects are
      musicians). Data of other kinds suggest that, if pure-tone pitch height were a
      function of place, the place could be the apical excitation-pattern edge, in any
      case not a maximum, which in neural data shifts and disappears with tone level.

PMID- 9007586
TI  - Prevalence of antibodies against HEp-2 cell antigen in infants and children
      hospitalized with respiratory syncytial virus infection.
AB  - Infants with respiratory syncytial virus (RSV) infection were shown to have
      antibodies against HEp-2 cell antigen present in RSV-antigen preparation used for
      immunoblot analysis. The prevalence of anti HEp-2 cell antibodies was examined in
      infants hospitalized for RSV infection (n = 49, median age 121 days) compared to
      rotavirus infected children (n = 30, median age 114 days) and to healthy controls
      (n = 20, median age 150 days). The immunoblot analysis with RSV-infected and non
      infected HEp-2 cells as antigen revealed the expected age-dependent low
      prevalence of G protein antibodies and clear seroconversion of N and P protein
      antibodies. HEp-2 antibody prevalence was higher in RSV antigen-positive infants
      (33/49) than in rotavirus antigen-positive (5/30) and RSV antigen-negative
      infants (4/20), respectively (p < 0.001). Anti HEp-2 antibodies were mostly
      directed against 47, 46, 33, 30 kD antigens. A multiple regression analysis found
      the following correlations (odds ratio; 95% confidence interval): 42 kD RSV
      antibodies (N protein) with pneumonia (7.58; 1.43-40), 94 kD RSV antibodies (G
      protein) with bronchiolitis (0.064; 0.006-0.686). This study shows repeated well
      known features of humoral immunity in RSV infection. The data on anti HEp-2
      antibodies point to a role for these pre-existing autoreactive antibodies in the
      pathogenesis of RSV infection.

PMID- 9007587
TI  - Quantitative molecular monitoring of HIV-1 RNA during antiretroviral therapy.
AB  - Plasma HIV-1 RNA testing was used to monitor 43 HIV-1 infected patients newly
      placed on antiretroviral therapy or whose therapy had been recently changed. A
      polymerase chain reaction kit was used to measure HIV-1 RNA in clinical samples
      or frozen plasma. The cutoff of this test was 200 RNA copies/ml. The first group
      (11 patients) was stable on long-term zidovudine monotherapy when switched to
      stavudine. The HIV-1 RNA of three patients who had a regular decline in CD4+ T
      cell count did not change despite this switch, with a mean follow-up of 630 days.
      The HIV-1 RNA copy numbers of eight patients whose CD4+ T cell counts were stable
      declined an average of 0.53 log10 between days 90 and 650. The second group (14
      patients) was on long-term zidovudine monotherapy and had declining CD4+ T cell
      counts over the past 6 months. Lamivudine was added to this regimen on day 0. HIV
      1 RNA copy number decreased rapidly within 30 d, reaching -0.86 log10 on day 90,
      and this effect was maintained thereafter, with a mean follow-up of 161 days.
      There was a concomitant mean gain of +33 CD4+ T cells on day 90. The third group
      (nine patients) had never received anti-retroviral therapy and was given
      zidovudine+didanosine. HIV-1 RNA copy number decreased in all cases but one,
      reaching -1.31 log10 on day 150. This decrease was transient in three cases. The
      last group (nine patients) had also not had previous anti-retroviral therapy and
      was given zidovudine + didanosine + lamivudine in combination. HIV-1 RNA copy
      numbers declined rapidly in all cases, to below the cutoff in eight cases within
      a mean period of 50.5 days. The CD4+ cell counts increased by 164
      cells/microliter on day 14 and by 201 cells/microliter on day 180. The response
      to therapy of the total population of 43 patients varied according to cases. The
      relative changes in p24 antigen compared to HIV-1 RNA also differed between
      patients. Measurement of HIV-1 viremia appears to be a valuable tool in current
      practice for individualizing therapy.

PMID- 9007589
TI  - A randomized study comparing fluconazole with amphotericin B/5-flucytosine for
      the treatment of systemic Candida infections in intensive care patients.
AB  - In this prospective, randomized study fluconazole and amphotericin B/5
      flucytosine were compared in the treatment of systemic candidiasis. Seventy-two
      non-neutropenic intensive care patients with systemic Candida infections were
      enrolled. Thirty-six patients were randomly assigned to receive fluconazole (400
      mg on the first day then 200 mg) and 36 were randomized to amphotericin B/5
      flucytosine (1.0-1.5 mg/kg body weight every other day and 3 x 2.5 g
      flucytosine/day) for 14 days following the diagnosis. There was no statistically
      significant difference in clinical outcome in regard to the treatment of
      pneumonia and sepsis: 18/28 of the patients were treated successfully with
      fluconazole and 17/27 with amphotericin B/5-flucytosine. For the treatment of
      peritonitis, however, amphotericin B/5-flucytosine was more effective than
      fluconazole (55% vs. 25%). Furthermore, amphotericin B/5-flucytosine was found to
      be superior to fluconazole with regard to pathogen eradication (86% vs. 50%).
      Fluconazole was associated with less toxicity than amphotericin B/5-flucytosine.

PMID- 9007588
TI  - Zidovudine resistance mutations and human immunodeficiency virus type 1 DNA
      burden: longitudinal evaluation of six patients under treatment.
AB  - Zidovudine (ZDV) is by far the most widely used drug to counteract human
      immunodeficiency virus type 1 (HIV-1) infection, both in monotherapy and in
      combination therapy regimens. However, the majority of patients under prolonged
      ZDV therapy have been shown to harbour HIV-1 mutant genomes displaying reduced
      sensitivity to the drug in vitro. In order to investigate the pathogenic role of
      in vitro resistance to ZDV, six HIV-1-infected ZDV-treated subjects were
      evaluated longitudinally (mean follow-up 28.5 months, range 12-39 months) for HIV
      1 DNA load in peripheral blood mononuclear cells (PBMC) and for the presence of
      HIV-1 pol gene mutations responsible for ZDV resistance. Quantitation of HIV-1
      DNA was performed by competitive polymerase chain reaction (cPCR) and the pol
      genotype was determined by direct sequencing of PCR products. All of the six
      patients developed one or more of the HIV-1 pol mutations known to confer
      resistance to ZDV in vitro (Met41-->Leu, Asp67-->Asn, Lys70-->Arg, Thr215-
      >Phe/Tyr, Lys219-->Gln/Glu). A temporal association was found between HIV-1 DNA
      burden and the level of ZDV resistance, as predicted on the basis of the pol
      genotype (genotypic resistance). Both virus load and ZDV resistance were
      inversely correlated with CD4+ cell counts. These results are compatible with a
      direct in vivo pathogenetic role for pol gene mutations shown to be involved in
      resistance to ZDV in vitro. Monitoring the degree of genotypic resistance to ZDV
      and to other antiretroviral drugs should be considered in designing protocols for
      the management of treated patients.

PMID- 9007590
TI  - Procalcitonin in patients with and without immunosuppression and sepsis.
AB  - High serum levels of procalcitonin (PCT) are observed in patients with sepsis or
      severe infection. In a prospective study of 122 hospitalised adult medical
      patients with sepsis, serum PCT was determined on admission and for 9 days
      thereafter. Patients with no alteration in their immune system showed high PCT
      values up to day 5, decreasing to normal levels by day 9. Patients with sepsis
      and immunodeficiency had high values on days 0 to 2, similar to the first group,
      but showed significantly lower levels on the following 3 days. PCT concentrations
      fell to base line levels on days 6 to 9 of the sepsis episode in both groups. The
      observed difference was not significantly related to the kind of causative
      microorganism or a culture negative sepsis. Leukopenia seemed to go together with
      lower PCT values after day 2 of the episode, but this could not be proven
      statistically.

PMID- 9007591
TI  - Reinfection in Lyme borreliosis.
AB  - Two patients with reinfection of Borrelia burgdorferi are presented. An 11-year
      old girl developed recurrent acute peripheral facial palsy at an interval of five
      years. A 64-year-old woman showed paraesthesia in the leg and effusion in the
      knee. Three years later, an erythema migrans developed at the thigh. In both
      patients tick bites, corresponding clinical manifestations, and detection of
      specific antibodies proved the reinfections. The course of the humoral immune
      responses showed basic differences between the patients. At the interval between
      the first and second infection, the specific antibodies of the girl decreased
      beyond the cut-off level. On the other hand, the titer of specific IgG antibodies
      of the other patient remained at a constant level. Reasons for the failure of
      immune protection are discussed.

PMID- 9007592
TI  - High prevalence of opportunistic infections in the head and neck related to human
      immunodeficiency virus. A prospective study of the distribution of
      otorhinolaryngologic disorders in 250 patients.

PMID- 9007595
TI  - Epidemiology of tick-borne encephalitis virus in Germany.

PMID- 9007594
TI  - Postantibiotic effect of ceftriaxone and gentamicin alone and in combination on
      Klebsiella pneumoniae, Pseudomonas aeruginosa and Streptococcus viridans.
AB  - A persistent suppression of bacterial growth following limited exposure to an
      antimicrobial agent, the postantibiotic effect (PAE), has been described for a
      variety of antibiotics and microorganisms. In this study the PAE of ceftriaxone
      and gentamicin was determined in vitro on three strains each of Klebsiella
      pneumoniae, Pseudomonas aeruginosa and Streptococcus viridans. The strains were
      exposed to the substances for 2 h at varying concentrations. Ceftriaxone was used
      at the minimal inhibitory concentration (MIC) and 1/2 MIC and gentamicin at 1/2
      MIC, 1/4 MIC, and 1/8 MIC, each alone and in combination. Antibiotic
      concentrations were reduced by 1,000-fold dilution, bacterial regrowth was
      consequently monitored by viable count. The PAE of ceftriaxone alone reached up
      to 145 min (MIC) and 50 min (1/2 MIC), that of gentamicin alone up to 170 min
      (1/2 MIC), 135 min (1/4 MIC) and 70 min (1/8 MIC), depending on the bacterial
      species. Combinations of the antibiotics produced longer PAEs than one substance
      alone; the longest PAE was produced by the combination of ceftriaxone (MIC) and
      gentamicin (1/2 MIC) lasting up to 320 min (S. viridans). It may be important to
      take the PAE into account when evaluating dosing intervals.

PMID- 9007593
TI  - Clinical development of a new inactivated hepatitis A vaccine.

PMID- 9007596
TI  - Neurologic manifestation and classification of borreliosis.
AB  - The neurologic symptoms of borreliosis can be classified to give distinct
      clinical pictures. The exact clinical characterisation allows an unambiguous and
      applicable classification of the different neurologic manifestations to be made.
      Due to high background seroprevalence of anti-Borrelia antibodies this
      classification is crucial for diagnosis. The most frequent neurologic
      manifestation is meningopolyradiculitis. It shows a typical pattern of symptoms,
      yet for differential diagnosis the crucial symptoms are the severe pains and the
      paresis of cranial nerves. In up to 10% of these patients no specific intrathecal
      antibody production was identified due to the time factor. Intrathecal antibody
      production cannot therefore be considered as the exclusive criterium for
      neuroborreliosis.

PMID- 9007597
TI  - Lyme borreliosis--problems of serological diagnosis.
AB  - As long as test procedures are not standardized, the serological results of IgM-
      and IgG-antibodies in Lyme borreliosis must be interpreted with caution and
      always in the context of clinical signs and symptoms. False negative results
      occur primarily during the first weeks of infection. In erythema migrans of less
      than 4 weeks' duration, 50% of patients are seronegative even with newly designed
      ELISAs. At this early stage of the infection the therapeutic decision has to be
      established on the basis of clinical criteria. Frequently IgM- and/or IgG
      antibodies develop during antibiotic therapy. After 4 weeks' duration 80% of
      patients have elevated borrelial antibodies detectable with recently developed
      ELISAs. Positive and borderline results should be confirmed by Western blot.
      False positive results, particularly slightly elevated IgM, may occur in a
      variety of other diseases. Another problem is the persistence of Borrelia
      specific IgM antibodies after therapy. Serological follow-up can only be carried
      out with the same methods in the same laboratory. Retreatment should be
      considered if IgM antibodies are increasing significantly and new symptoms are
      occurring.

PMID- 9007598
TI  - Meropenem monotherapy versus cefotaxime plus metronidazole combination treatment
      for serious intra-abdominal infections.
AB  - In an open, randomised, multicentre trial, the efficacy and tolerability of
      empirical meropenem monotherapy (1 g intravenously every 8 hours) and cefotaxime
      (2 g every 8 hours) plus metronidazole (0.5 g intravenously every 8 hours) for 5
      to 10 days was compared in 94 patients with serious intra-abdominal infection who
      required surgery. Eighty-three patients had an evaluable clinical response.
      Significantly more patients in the meropenem group had a satisfactory clinical
      response at the end of treatment (41/43 [95.3%] vs 30/40 [75.0%]; p = 0.008). The
      bacteriological response was also higher in the meropenem group (31/33 vs 26/32).
      In the bacteriologically evaluable population, a satisfactory clinical response
      was observed in 31/33 of those who received meropenem compared to 24/32 of the
      cefotaxime/metronidazole recipients (p = 0.03). Empirical meropenem monotherapy
      should prove a useful alternative to the currently standard combination treatment
      for serious intraabdominal infections.

PMID- 9007600
TI  - Competition and quality: friends or foes?

PMID- 9007599
TI  - Empirical monotherapy with meropenem versus imipenem/cilastatin for febrile
      episodes in neutropenic patients.
AB  - In a nonblind, randomised, parallel-group study, initial empirical monotherapy
      with meropenem 1 g intravenously every 8 h was compared to an identical dosage of
      imipenem/cilastatin for the treatment of 66 febrile episodes in 61 adult
      neutropenic patients. 25/31 episodes treated with meropenem and 24/30
      imipenem/cilastatin-treated episodes were still receiving unmodified therapy at
      72 h (primary endpoint); this difference was not statistically significant. By
      the end of the treatment courses, 18/31 meropenem-treated episodes had responded
      clinically (cured or improved) compared with 18/30 episodes treated with
      imipenem/cilastatin. Another ten episodes initially treated with meropenem and
      six episodes treated with imipenem/cilastatia were cured after an additional
      antimicrobial agent had been administered (cured with modification). Satisfactory
      bacteriological responses (eradication plus presumed eradication) at the end of
      unmodified therapy was 9/11 in the meropenem group and 14/16 in the comparator
      group. Both regimes were well tolerated; however, there were more reports of
      nausea and/or vomiting in the impenem/cilastatin group (7/33 vs. 2/33 in the
      meropenem group). The carbapenems meropenem and imipenem/cilastatin appear to be
      suitable agents for empirical monotherapy of febrile episodes in neutropenic
      patients. Meropenem may be better tolerated than imipenem/cilastatin, allowing
      optimal dosing in this patient population.

PMID- 9007602
TI  - Impact of hospital and community provider based clinical audit programmes:
      perceptions of doctors, nurses and other health professionals.
AB  - A postal survey of staff (doctors, nurses, midwives, health visitors, therapy
      professionals, senior managers and clinical audit staff) was conducted in three
      English hospital and community healthcare providers. The aim was to assess staff
      perceptions of the impact of local clinical audit programmes and to investigate
      differences between staff groups. The questionnaire contained a 24 item opinion
      scale with a summary total: 371 out of 566 questionnaires were returned completed
      (66%). The majority of respondents were positive about the impact of clinical
      audit in their organizations, which is encouraging. However, there was a wide
      range of responses and significant variations between professional groups.
      Medical staff were significantly less positive than non-medics (p = 0.0007), and
      junior staff significantly less positive than seniors (p = 0.0306 for doctors and
      p = 0.0013 for other health care professions). After over five years experience
      of clinical audit in UK hospitals and community providers, many local staff
      remain sceptical about its real value.

PMID- 9007601
TI  - Influence of location and staff knowledge on quality of retail pharmacy
      prescribing for childhood diarrhea in Kenya.
AB  - BACKGROUND: Retail pharmacies are important sources of advice on pharmaceuticals
      in developing countries, where many purchasing decisions are unmediated by
      medical professionals. For childhood diarrhea, choice of drug sales in pharmacies
      has been found to be consistently poor, whether with or without prescription, as
      evidenced by a low use of effective oral rehydration salts (ORS) and high use of
      marginally effective or ineffective products such as antimotility agents,
      adsorbents, and antimicrobials. Little information is available about factors
      influencing prescribing by pharmacy personnel in these settings. This paper
      reports results of an analysis which examined the influence of rural versus urban
      location, neighborhood socio-economic status (SES), and clinical knowledge of
      pharmacy assistants on quality of prescribing in retail pharmacies in Kenya.
      METHODS: Using WHO treatment guidelines, we measured quality of prescribing in
      childhood diarrhea as: (1) the proportion of client encounters in which ORS is
      prescribed (indicating higher quality practice); and (2) the proportion of visits
      in which an antidiarrheal product is prescribed (lower quality practice). We
      obtained data on prescribing in a simple case of childhood diarrhea using
      surrogate patient visits to 91 pharmacies located in the major urban area of
      Kenya (Nairobi) and four rural towns. Multivariate logistic regression was used
      to examine the association between pharmacy predictor variables and the quality
      of prescribing. RESULTS: No consistent relationship was found between the
      clinical knowledge of pharmacy assistants and quality of prescribing. Controlling
      for number of products prescribed, gender of the assessor, and level of
      knowledge, multivariate analyses indicated that in comparison to rural
      pharmacies, the odds of prescribing ORS were significantly higher in pharmacies
      located in high SES (OR = 4.7; 95% CI = 1.4,16.1) or middle SES (OR = 4.5; CI =
      1.9,10.6) urban neighborhoods; the odds in low SES urban pharmacies were similar
      to those in rural areas (OR = 2.0; CI = 0.6,6.2). The odds of prescribing
      antidiarrheal products did not differ significantly in any geographic area.
      CONCLUSIONS: Location of a retail pharmacy in a rural area or in a low-income
      urban neighborhood was associated with suboptimal quality of prescribing as
      evidenced by lower use of ORS. No relationship between clinical knowledge and
      quality of practice was detected. Future research is needed to examine such
      factors as the influence of intra-pharmacy authority structure, perceived
      efficacy of pharmaceuticals, local patterns of physician practice, and economic
      incentives on the quality of prescribing.

PMID- 9007603
TI  - Quality of documentation in medical reports of diabetic patients.
AB  - In a retrospective analysis of 752 consecutive medical reports of patients with
      insulin- or non-insulin-dependent diabetes mellitus, we investigated the
      completeness of documentation of indicators of quality of care. The medical
      reports are the currently used form of documentation which is sent to the General
      Practitioner after the patient's discharge from hospital. The indicators of care
      were data on clinical history, physical examination, laboratory results and
      secondary complications. The documentation was incomplete; e.g. in 8.0% of
      insulin-dependent (IDDM) and in 26.4% of non-insulin-dependent diabetics (NIDDM),
      HbA1c was missing. In 7.6%, the type of diabetes was not stated. The frequency of
      recorded secondary complications was lower than it has to be expected considering
      metabolic control and duration of diabetes of the studied group. Documentation
      was more complete for IDDM patients. The reports of NIDDM patients with incipient
      or overt diabetic nephropathy revealed less frequent recordings of data on lipid
      metabolism and blood pressure compared to the group without nephropathy. The
      documentation of indicators of quality of care in medical reports for general
      practitioners is incomplete for many diabetic inpatients. Standardized methods of
      documentation are required urgently.

PMID- 9007604
TI  - Appropriateness of admission and the last 24 hours of hospital care in medical
      wards in an east London teaching group hospital.
AB  - OBJECTIVE: To assess the rates of inappropriateness of admission and last day of
      care on adult medical wards in an east London hospital, to identify associations
      with any inappropriateness and to assess what services need to be improved or
      provided if patients assessed as "inappropriate" are to be more appropriately
      placed in the future. DESIGN: From the patients' medical notes, nursing notes and
      ward charts, a trained reviewer with nursing and university qualifications
      collected concurrent information about each patient's first 24 hours as an in
      patient and about the last 24 hours of care preceding discharge. Patients were
      also interviewed before discharge and 7-10 days after discharge, and their health
      status and level of satisfaction about the discharge process assessed. SETTING:
      The three adult medical wards at the Homerton Hospital in Hackney, east London.
      This hospital is within the St Bartholomew's Hospital Teaching Hospital Group.
      SUBJECTS: The case-notes of a random sample of 625 adult in-patients were
      reviewed. END POINTS: Appropriateness of admission and last day of care. MAIN
      OUTCOME MEASURES: The main instrument used was the Appropriateness Evaluation
      Protocol (AEP). This is an instrument devised to assess the appropriateness of
      adult patient admission to, and specific days of care in, acute hospital beds
      through case-note review against a structured set of criteria. RESULTS: The study
      presented here reported that 31% of in-patient admissions to adult medical wards
      in an east London hospital were inappropriate, and also that 66% of the last days
      of stay were inappropriate. CONCLUSIONS: There is clearly considerable room for
      improvement in relation to cooperation between service providers in order to
      maximise efficient bed use. Delays due to waiting for medications from pharmacy,
      and the combination of more "inappropriate" cases wanting help from social
      services after discharge with the fact that many of them were still in hospital
      because they were waiting for these services to be organized, suggest that
      inappropriateness could be reduced through increased efficiency or increased
      provision in these areas. The study reported here is unique in its inclusion of
      patient interview data.

PMID- 9007605
TI  - The development and application of a patient satisfaction measurement system for
      hospital-wide quality improvement.
AB  - A regional Swedish hospital has been the site of a quality improvement program
      that focuses on patient satisfaction, staff work environment and quality of
      hospital services. This article describes the study component that measures
      patients' views of the quality of care. The purpose of this study was to develop
      a reliable and valid instrument, to determine the predictors of patients' ratings
      of quality and to measure patient satisfaction at two points in time to determine
      whether patient ratings change following a quality improvement initiative. The
      instrument developed in this study was designed to assess patients' perceptions
      of the quality of hospital services, staff work environment and overall
      satisfaction for the purpose of providing feedback to hospital staff. This
      information would be used for quality improvement efforts within the hospital.
      Unique to this instrument are questions regarding patients' perceptions of the
      hospital staff work environment. The results revealed that the questionnaire
      demonstrated valid and reliable properties. The significant predictors of quality
      ratings were information concerning one's illness, and perceptions of the staff
      work environment. Patient satisfaction was measured and then reassessed following
      the implementation of various department-based improvement programs. The
      reassessment revealed significantly higher patient ratings in most areas. An
      intrinsic aspect of this quality program was the engagement of, and feedback
      process to, hospital personnel. Questionnaire results were reported graphically
      to hospital management and staff, thus serving as a catalyst for improvement.

PMID- 9007606
TI  - Quality of work incapacity assessment in the Swiss disability insurance system.
AB  - Quality of medical assessment of work incapacity has been poorly investigated,
      despite the enormous costs engendered by transient incapacity of work and
      permanent disability. This study examined some indices of quality from a
      stratified, random sample (n = 120) of assessments performed by expert assessors
      of the Swiss disability insurance. The distribution of work incapacity (WI)
      percentages over a 100% scale showed a clustering around key values significantly
      associated with financial disability benefits. The precision of WI, expressed as
      the level of quantitative exactness, was found to be high in 74% (95% CI: 66-82%)
      of current WI assessments, and in 62% (95% CI: 53-71%) of maximal WI assessments.
      Disagreement was observed in 17% of cases when comparing two ways of expressing
      WI by the same physician (95% CI: 10-23%). This exploratory study is limited by
      the general lack of objective criteria and standards. Further theoretical and
      empirical developments are needed to determine standardized criteria and clear
      guidelines for medical assessments of WI, as well as for evaluating their
      quality.

PMID- 9007607
TI  - Preliminary report of data collection in hospital quality assurance programs--a
      project of the Association of Hospitals of the Czech Republic.
AB  - OBJECTIVES: This was the first attempt of the association representing all acute
      care hospitals in the Czech Republic to collect mutual data which might be used
      for quality assurance (QA) purposes and which might lead to the development of
      national standards of care which could be used for hospital accreditation. Data
      collected included information which was available universally and which could be
      measured; in addition, information was intended to be similar in each hospital.
      In most cases, the data collection systems were based on financial information
      and data had to be identified which might be used for QA purposes, rather than
      being able to design a system specific for QA purposes. DESIGN: Since the
      hospital payment system was established in 1992, hospitals have had to develop
      data collection systems to measure clinical activity; this current study was
      based on this data collection, adapted to QA purposes. SETTING: The Executive
      Committee of the Hospital Association agreed to a pilot study of hospitals in
      1993; data were collected from approximately 40 hospitals, beginning in 1994.
      STUDY PARTICIPANTS: Hospitals were chosen based on their ability to collect data
      and participate in the program, and it was determined that there should be
      variability in the hospitals, in size, location and activities, but that the data
      collected should be generic. INTERVENTIONS: Raw data included 33 different items,
      most of which were irrelevant to QA. Using a computer program, various
      combinations of data were reviewed and evaluated to ascertain the most
      appropriate for QA purposes. MAIN OUTCOME MEASURES: Data were chosen for study
      which included (a) data from the largest departments in the individual hospitals;
      (b) length of stay for patients hospitalized in these departments; (c) number of
      occupied beds/physician in the department and (d) mortality/1000 admissions to
      the department. RESULTS: The combination of (1) a long length of stay; (2) a high
      occupied bed/doctor ratio; and (3) a high mortality rate/1000 admissions might be
      indicators of poor quality. Additional factors to consider include: the type of
      department-emergency, cancer, geriatric, etc.; the nature of the medical activity
      acute, referral, primary care, etc.; whether or not "social" beds are included
      and, generally, comparability among departments. However, as a pilot study,
      certain indicators can be determined which then can be used for future study to
      determine quality of care. The ability to cooperate and collect seemingly
      comparable data indicates reason for optimism in the future; more detailed and
      accurate studies can be carried out which will enable assessment of the quality
      of care given in comparable situations in hospitals throughout the Czech
      Republic.

PMID- 9007608
TI  - Accreditation programs for hospitals: funding and operation.
AB  - Accreditation is a formal process by which an authorized body assesses and
      recognizes an individual, an organization (like a hospital), a program, or a
      group as complying with requirements such as standards or criteria. This article
      analyses and compares the activity and funding of six health care accrediting
      bodies which operate in five different countries, and which in 1994, accredited
      over 5000 health centres. The data included in this article could be useful for
      other institutions who wish to commence accreditation programmes for health care
      organizations.

PMID- 9007609
TI  - Quality problems that result in adverse outcomes provide opportunities for
      quality improvement.
AB  - Patient suffers central nervous system damage after prolonged use of
      metoclopramide and ranitidine hydrochloride to control gastroesophageal reflux.
      Treatment is complicated by poor communication among providers and omissions in
      history-taking.

PMID- 9007610
TI  - The role of chemokines in inflammation.
AB  - Chemokines, together with adhesion molecules, cytokines, and proteases, are
      essential for the directional migration of leukocytes during normal and
      inflammatory processes. Interleukin-8 and monocyte chemotactic protein-1 are the
      best-characterized members of the C-X-C and C-C chemokine subfamilies,
      respectively. However, more than 20 human chemokines have been identified but are
      only partially characterized at the biological level. Chemokines are involved in
      chemotaxis of monocytes, lymphocytes, neutrophils, eosinophils, basophils,
      natural killer cells, dendritic cells, and endothelial cells. This review
      describes the chemokine subfamilies, the chemokine producer and target cells,
      their receptors, signal transduction mechanisms, and the role of chemokines
      during physiological and pathological conditions. More and more evidence points
      to a role for chemokines in chemotaxis-related phenomena, such as the expression
      of adhesion molecules, the secretion of proteinases, inhibition of apoptosis,
      hematopoiesis, and angiogenesis. Chemokines are also involved in diseases such as
      cancer (tumor regression and tumor metastasis), autoimmune diseases, and
      bacterial or viral infection.

PMID- 9007611
TI  - Apolipoprotein AIV of human interstitial fluid is associated with apolipoprotein
      AI-containing but not with AII-containing particles.
AB  - Apolipoproteins and lipoprotein particles from human interstitial fluid and
      plasma were analyzed. The interstitial fluid was enriched in apolipoproteins AI,
      AII, and AIV compared with apo B, apo CIII, and apo E, LpAI was found to contain
      apo AIV which was absent from LpAI: AII. Moreover, the bulk of lecithin
      cholesterol acyl-transferase was present in LpAI. The concentration range of
      these particles was in agreement with those required in vitro for cholesterol
      efflux. Thus the interstitial fluid contains particles in which two agonists but
      no antagonists of cholesterol efflux are associated with lecithin-cholesterol
      acyltransferase activity. This supports apolipoprotein AI- and/or AIV-containing
      particles playing a critical role in the first step of reverse cholesterol
      transport.

PMID- 9007612
TI  - The effect of cefodizime on phagocyte function in non-patient volunteers and
      patients with chronic renal failure. In vitro and ex vivo studies.
AB  - Cefodizime has previously been shown to possess a number of immunomodulating
      properties in vivo and in vitro using several different test systems. Since most
      in vitro studies have been performed with cells from normal individuals, we first
      investigated whether cells from chronic renal failure patients would respond in
      vitro to cefodizime in the same way as healthy subjects. Subsequently, we
      investigated the effect of cefodizime (10 g over 10 days in 2-g doses) on
      phagocyte function ex vivo in an open study of 26 chronic renal failure patients
      and 16 healthy subjects. Polymorphonuclear leukocytes were tested for their
      ability to polarize in response to cefodizime and/or f-met-leu-phe peptide.
      Polymorphonuclear leukocytes and monocytes were tested for their ability to
      produce chemiluminescence on stimulation with either phagocytic (zymosan) or
      soluble phorbol myristate acetate stimuli. Phagocyte and lymphocyte membrane
      receptor expression was compared after exposure to cefodizime. Exposure to
      cefodizime in vitro causes a significant increase in polarization of
      polymorphonuclear leukocytes from both normal individuals and renal failure
      patients (both P < 0.001). It also caused increased chemotaxis and chemokinesis
      in a modified Boyden chamber assay. Cefodizime did not affect lucigenin-enhanced
      chemiluminescence and there were only minor effects on cell membrane antigen
      levels. In the ex vivo study there was a significant increase in
      polymorphonuclear leukocyte polarization (P < 0.001) attributable to cefodizime,
      but other investigations showed no significant differences. The results suggest
      that cefodizime may act as a mild priming agent for some functions, particularly
      chemotaxis.

PMID- 9007613
TI  - Priming of neutrophils with tumor necrosis factor-alpha measured as Fc gamma
      receptor-mediated respiratory burst correlates with increased complement receptor
      3 membrane density.
AB  - Hyperactive or primed neutrophils which damage tissue via cytokines and membrane
      receptors may be implicated in the pathogenesis of inflammatory conditions. The
      purpose of this study was to elucidate the priming mechanism in neutrophils by
      assessing changes in membrane receptors and the Fc gamma R-mediated respiratory
      burst, measured as chemiluminescence. Purified neutrophilic granulocytes from
      healthy volunteers were preincubated with recombinant human tumor necrosis factor
      alpha. This had a priming effect, increasing both the Fc gamma receptor-mediated
      luminol-enhanced chemiluminescence and the membrane expression of the C3bi
      receptor (CRB) (r = 0.843). The membrane densities of Fc gamma RII, Fc gamma
      RIII, and CR1 were unaffected by tumor necrosis factor-alpha. The mechanism of
      increased chemiluminescence may involve redistribution of the Fc gamma receptors
      and cooperation with upregulated CR3, facilitating crosslinking of the receptors.
      The experiments were performed in a buffer without divalent cations, since these
      increased the background activity and abolished the priming effect of tumor
      necrosis factor-alpha. In conclusion, a simultaneous increase in the Fc gamma R
      mediated respiratory burst and CR3 density after priming with tumor necrosis
      factor-alpha indicates a cooperation between Fc gamma R and CR3.

PMID- 9007614
TI  - Cytokines may influence tumor growth and spread. An in vitro study in two human
      cancer cell lines.
AB  - Tumor spread may be favored by a reduced production and/or an enhanced
      degradation of extracellular matrix components (collagen, fibronectin, laminin).
      Most tumor cell behavior, from growth to spread, may be regulated by cytokines,
      the exact roles of which, however, are not yet fully understood. We here evaluate
      the effects of some cytokines (epidermal growth factor, transforming growth
      factor-beta 1, interleukin-1 alpha, and interleukin-1 beta) on both cell growth
      and the production of the aminoterminal peptide of type III procollagen, the
      urokinase plasminogen activator, and the plasminogen activator inhibitor-1 in
      neoplastic cell lines originating in the pancreas and colon. Cells were
      stimulated daily with the above cytokines and the aminoterminal peptide of type
      III procollagen, urokinase plasminogen activator, and plasminogen activator
      inhibitor-1 were measured in the conditioned media. Epidermal growth factor
      stimulated cell growth of both cell lines. Transforming growth factor-beta 1
      counteracted cell proliferation and stimulated type III procollagen and
      plasminogen activator inhibitor-1 production only in the colon cancer cell line.
      Interleukin-1 alpha slightly stimulated cell growth, but inhibited plasminogen
      activator inhibitor-1 production in both cell lines; interleukin-1 beta did not
      affect cell growth, but stimulated plasminogen activator inhibitor-1 production
      by the colon cancer cell line. Our findings suggest that transforming growth
      factor-beta 1 and interleukin-1 beta may have an antidiffusive effect. These
      results confirm that cytokine-producing cells have a potential role in
      stimulating or counteracting tumor growth and spread and also confirm the pivotal
      role of host-tumor interactions in determining the outcome of a particular
      neoplasia.

PMID- 9007615
TI  - Serum copper/zinc superoxide dismutase levels in patients with rheumatoid
      arthritis.
AB  - Rheumatoid arthritis is characterized by a chronic hypertrophic synovitis leading
      to destruction of connective tissue and functional damage of cartilage and bone
      structures. Reactive oxygen species play an important role in tissue injury in
      this disease. To clarify the role of the cellular antioxidant system in the
      protection against oxygen free radicals, we examined the levels of copper/zinc
      superoxide dismutase in the sera of patients with rheumatoid arthritis. We used
      an enzyme-linked immunosorbent assay which determines the concentration of
      copper/zinc superoxide dismutase independently from its enzymatic activity. We
      found that patients with rheumatoid arthritis have higher serum copper/zinc
      superoxide dismutase levels than control subjects. Copper/zinc superoxide
      dismutase also correlated positively with serum levels of both neopterin and
      rheumatoid factor, sensitive markers for disease activity in rheumatoid
      arthritis. These results support the hypothesis that the increased amount of
      copper/zinc superoxide dismutase is probably inadequate to exert an effective
      antioxidant protection but can result in a pro-inflammatory, pathogenic effect
      enhancing tissue damage. Furthermore, copper/zinc superoxide dismutase might be
      used as a marker of inflammatory activity in rheumatoid arthritis.

PMID- 9007616
TI  - A novel missense mutation (Asn5-->Ile) in lecithin: cholesterol acyltransferase
      (LCAT) gene in a Japanese patient with LCAT deficiency.
AB  - We identified a novel missense mutation in the lecithin:cholesterol
      acyltransferase gene in a new case of lecithin:cholesterol acyltransferase (LCAT)
      deficiency. The patient was a 64-year-old diabetic Japanese male who showed an
      extremely low level of serum high-density lipoprotein-cholesterol, corneal
      opacities, anemia, and proteinuria. Both the patient's LCAT activity and mass
      were markedly low. DNA sequence analysis of the LCAT gene showed an A-to-T
      transition at base 97 in exon 1, and predicted a change in asparagine to
      isoleucine at the 5th amino acid of the protein. Restriction analysis of
      polymerase chain reaction-amplified DNA using Ase I showed that the patient was
      homozygous for this mutation. Our results suggested that asparagine 5 was an
      important amino acid and substitution with isoleucine caused marked reduction of
      LCAT activity and mass, resulting in LCAT deficiency.

PMID- 9007617
TI  - Functional characteristics of cord blood T lymphocytes after lectin and anti-CD3
      stimulation. Differences in the way T cells express activation molecules and
      proliferate.
AB  - Newborns are more susceptible than adults to infections, which suggests a
      relative immaturity of the immune system early after birth. Cord blood T cells
      differ significantly both in surface phenotype and function from adult T cells.
      We examined the proliferation and expression of activation molecules by
      lymphocytes isolated from umbilical cord blood or peripheral blood of adults. The
      lymphocytes were cultured for 5 days in the presence of phytohemagglutinin,
      concanavalin A, or anti-CD3 monoclonal antibody. Cord blood T cells expressed the
      CD45RA molecule, while a low proportion expressed the RO isoform, a marker of
      primed or activated lymphocytes. Furthermore, more than 95% of neonatal
      lymphocytes bear the CD38 molecule, but do not express the CD57 molecule. After
      stimulation by phytohemagglutinin or concanavalin A, the lymphocytes from
      newborns were activated and proliferated as efficiently as adult T cells. Anti
      CD3 did not cause neonatal lymphocytes to proliferate, but these cells expressed
      activation molecules, such as HLA-DR antigens and the receptor for interleukin-2
      and transferrin. The relevance of these findings to tolerance induction in
      immature cord blood T cells is discussed.

PMID- 9007618
TI  - Transgenic mice expressing human phospholipid transfer protein have increased
      HDL/non-HDL cholesterol ratio.
AB  - The role of plasma phospholipid transfer protein (PLTP) in lipoprotein metabolism
      is poorly understood. In vitro studies suggest that PLTP influences HDL size and
      composition and transfers phospholipids among lipoproteins. To provide an in vivo
      model for studies of PLTP physiology, transgenic mice that express human PLTP
      were generated. Human PLTP transcripts were detected in total RNA from adipose
      tissue, lung, heart, and spleen of the two distinct lines (A and C) of transgenic
      mice. Despite minimal expression of human PLTP in the liver of these transgenic
      mice and similar plasma phospholipid transfer activity in transgenic and non
      transgenic mice (19.1 +/- 3.1 vs 18.9 +/- 2.7 mumol/ml/h), differences in
      lipoprotein levels were observed between transgenic and control mice receiving
      the same chow diet. Male transgenic mice of line C had significantly higher HDL
      cholesterol than control mice (76.4 +/- 4.6 vs 71.9 +/- 7.0 mg/dl, p < 0.05) and
      the male transgenic mice of lines A and C had a significantly lower non-HDL
      cholesterol (15.1 +/- 4.1 and 15.6 +/- 4.7 vs 20.9 +/- 5.5 mg/dl, P < 0.01 and P
      < 0.02) and a significantly higher HDL cholesterol/non-HDL cholesterol ratio than
      the control mice (5.3 +/- 1.3 and 5.5 +/- 2.2 vs 3.9 +/- 1.9 mg/dl, P < 0.01 and
      P < 0.02). Female mice from transgenic line C had higher HDL cholesterol than
      control mice (64.6 +/- 4.8 vs 57.4 +/- 5.1 mg/dl, P < 0.01) while female mice
      from line A tended to have higher HDL cholesterol/non-HDL cholesterol ratio than
      control mice (5.5 +/- 3.7 vs 3.8 +/- 1.4). These observations suggest that
      expression of PLTP in peripheral tissues play an important role in lipoprotein
      metabolism. Expression of human PLTP produced a more favorable lipoprotein
      profile and thus, enhanced expression of PLTP could potentially retard
      atherosclerosis.

PMID- 9007619
TI  - The use of glyceryl trinitrate in inexaminable patients with anal fissure.

PMID- 9007620
TI  - Enteric innervation in idiopathic megarectum and megacolon.
AB  - We have studied the resection specimens from 5 patients with idiopathic
      megarectum and megacolon and 10 control subjects with non-obstructing colonic
      cancer. Histological staining with haematoxylin and eosin, and immunocytochemical
      staining for protein gene product 9.5 (PGP9.5), S100 protein, vasoactive
      intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP), and
      histochemical localization of NADPH diaphorase was performed. The amount of VIP
      and CGRP present in samples was measured using an enzyme-linked immunosorbent
      assay. Patients with idiopathic megarectum and megacolon showed hypertrophy of
      the muscularis mucosae and muscularis externa. The architecture of the
      innervation as assessed by immunoreactivity for PGP9.5 and S100 protein appeared
      normal. There was a decrease in the density of innervation of the longitudinal
      muscle in rectal tissue from patients with idiopathic megarectum, with fewer VIP-
      and NADPH-diaphorase-containing nerves. In the muscularis mucosae and lamina
      propria of the rectal samples of patients with idiopathic megarectum, VIP
      immunoreactivity was higher and more NADPH-diaphorase-containing nerves were
      seen. CGRP-immunoreactive nerve fibres were only seen in the myenteric plexus. No
      CGRP-immunoreactive cell bodies were seen. In summary, there is an increase in
      VIP and nitric oxide containing fibres in the muscularis mucosae and lamina
      propria and a decrease in the longitudinal muscle in rectal tissue of patients
      with idiopathic megarectum. Both are NANC (nonadrenergic noncholinergic)
      inhibitory transmitters in the gut and the possible relationship of the changes
      in their density with gut function is discussed.

PMID- 9007621
TI  - Evaluation of digitally guided fine needle aspiration cytology versus fine needle
      core biopsy for the diagnosis of recurrent rectal cancer.
AB  - The clinical value of transrectally digitally guided fine needle aspiration
      cytology (FNAC) was compared with fine needle core biopsy (FNCB), FNAC was
      performed with a 21G and FNCB with a 18G needle. No prophylactic antibiotic was
      given. In the first part of the study 100 patients (20 primary/80 recurrences, 17
      benign/83 cancers) were studied by both techniques. In 93% a definite diagnoses
      was given in FNAC specimen versus 96% of the FNCB cases. There were no false
      positive cancer diagnoses. The sensitivity of the FNAC was 88% versus 68% of the
      FNCB specimens. This difference was statistically significant. In a second part
      of the study 142 specimens of recurrent cases were examined by FNAC including 78
      of the patients of the first part. The negative predictive value was around 60%
      for FNAC versus around 40% for FNCB. Both techniques were without any major
      complications. For the diagnosis of a palpable recurrent pelvic tumour a
      digitally guided puncture may be tried before proceeding to CT or US guided
      examination. In our hands FNAC seems preferable to FNCB.

PMID- 9007622
TI  - Life insurance and inflammatory bowel disease: is there discrimination against
      patients?
AB  - The aims of this study were to compare and contrast the attitude of major
      insurance companies to patients with inflammatory bowel disease (IBD) and to a
      Consultant Gastroenterologist (JFM) requesting guidelines for patients with IBD.
      The experience of patients in Leicester with insurance companies was also
      investigated. A standard letter requesting information regarding the likelihood
      of loading on life assurance in connection with a mortgage was sent to 50 major
      insurance companies from a typical patient. A similar letter was constructed from
      a consultant gastroenterologist (JFM) to the same 50 insurance companies
      requesting simple guidelines for patients with IBD when applying for various
      types of insurance. A questionnaire investigating the experience of patients with
      IBD when applying for insurance was also sent to 100 patients with IBD selected
      at random from the Leicestershire data base of patients with Crohn's disease and
      ulcerative colitis, 39 insurance companies responded to the request for
      information by a typical patient, (response rate = 78%). 24 were split between
      those who thought the patient would be accepted at normal rates (n = 7) and those
      who would request an increased premium (n = 17). Only 27 companies replied to the
      letter by a consultant gastroenterologist requesting general guidelines,
      (response rate = 54%). There were only 17 overlapping replies to the two letters.
      Of these 17 overlapping replies, five companies (30%) informed the patient to
      expect increased premiums whilst advising the consultant a similar patient could
      expect normal rates. Six companies conferred (35%), telling both the patient and
      the consultant to expect normal rates. Either one or both of the remaining six
      companies (35%) felt unable to comment without either specific details of the
      patient or a medical examination. 69% of patients responded to the questionnaire.
      Over half (54%) had applied for an insurance policy. More than a third of
      patients had required either a medical examination (36%) or a report from their
      GP (41%) before being accepted for a policy. 39% of patients had received an
      additional loading on their policies because of IBD including two patients who
      had been turned down altogether. In conclusion patients with IBD are clearly
      discriminated against by insurance companies. Life tables should be amended to
      take account of the low mortality recognised in recent years. Patients should be
      aware of the difficulties that currently exist.

PMID- 9007623
TI  - Management of angiogram positive lower gastrointestinal hemorrhage: long term
      follow-up of non-operative treatments.
AB  - After positive mesenteric angiography for massive lower gastrointestinal
      hemorrhage, one is faced with a localized bleeding site and the therapeutic
      options of embolization, vasopressin infusion, observation, or operation. This
      review was designed to determine long term outcomes of angiographically
      controlled bleeding. All cases of mesenteric angiography for hemorrhage performed
      over a twelve year period were reviewed, with focus on those treated non
      operatively. A total of 37 patients had angiographically localized bleeding
      distal to the ligament of Treitz. Twenty-one patients were controlled with
      vasopressin, embolization, or spontaneous cessation. Only three patients had
      recurrent bleeding, at one month, one year, and eight years. No patients died
      from recurrent bleeding. Five patients died without any further bleeding; mean
      time to death was 2 years. Twelve patients had no further bleeding at a mean
      follow-up of 2.6 years. Bleeding controlled by any angiographic measure, was
      followed by recurrent bleeding in 14% without the need for operative
      intervention.

PMID- 9007624
TI  - Preoperative radiotherapy for resectable cancer of the middle-distal rectum: its
      effect on the primary lesion as determined by endorectal ultrasound using
      flexible echo colonoscope.
AB  - 20 patients with rectal cancer within 8 cm of the anal verge were studied.
      Endoscopic endosonography was carried out before and after pre-operative
      radiotherapy (45 Gy over three weeks). The local extent (tumour stage and
      diameter) was compared with the results of histopathological examination of the
      resected specimen after anterior resection or total rectal excision. The Tumour
      Regression Grade (TRG) and lymph node status were also estimated. Two patients
      were not evaluated endosonographically. Two (11%) of the remaining 18 patients
      showed ultrasound evidence of down staging (14/18 uT3/4 pre-radiotherapy: 12/18
      uT3/4 after) and tumour diameter was significantly reduced. Tumour Regression
      Grade estimation showed evidence of response to treatment, showing regression of
      more than 50% in 13 (65%) of cases. Involved nodes were less than 5 mm in
      diameter in 45% of cases. Histopathological evidence of nodal metastatic
      regression was seen in 13 (28%) of all involved nodes found. The ultrasonically
      determined response to radiotherapy may offer useful information in predicting
      outcome and possibly in selecting surgery.

PMID- 9007625
TI  - Morbidity of medical therapy for ulcerative colitis: what are we really saving?
AB  - AIM: The true morbidity, cost and disability of medical therapy for ulcerative
      colitis are seldom delineated and are even less frequently compared to analogous
      parameters associated with surgical therapy. Therefore, we sought to assess and
      contrast medical versus surgical therapy for patients hospitalized due to severe
      ulcerative colitis. MATERIALS AND METHODS: Patients were matched for age,
      duration and severity of disease based upon Truelove and Witts' activity index,
      colonoscopic and histologic appearance and APACHE (Acute Psychological and
      Chronic Health Evaluation) II scores. Morbidity, cost and disability of 20
      medically treated patients who required at least one hospital admission were
      compared to 20 patients treated by a three stage restorative proctocolectomy.
      Demographic data, number of hospital admissions, length of stay, total hospital
      charges including consultant's, surgeon's, and anesthesiologist's fees, morbidity
      of each approach and disability were assessed. Statistical analysis was performed
      using Mann-Whitney and Fisher exact tests. Significance was considered as P <
      0.05. RESULTS: The mean age was 53.6 years in the medical group and 48.1 years in
      the surgical group (P = NS) and the average duration of disease was 10.5 years
      and 9.5 years, respectively (P = NS). The same severity of pancolitis was noted
      in both groups; APACHE scores of 13 and 14 in the medical and surgical groups,
      respectively, were noted. The total number of hospital admissions and total
      combined length of stay per patient in each group were not significant. Total
      mean hospital cost for the medical group was $28,477.00 per patient versus
      $33,041.00 for the three stage restorative proctocolectomy (P = NS). The mean
      duration of disability in the medical group was 6.4 months per patient versus 5.0
      months in the surgical group (P = NS). However, patients in the medical group
      required more transfusions (25%) than did those in the surgical group (0%) (P <
      0.05) and significant weight loss was more common in the medical group (45%)
      compared to the surgical group (5%) (P < 0.01). All patients in the surgical
      group were permanently weaned from steroids. Furthermore, while 65% of patients
      in the medical group had significant steroid-related complications, the major
      surgical complication rate was only 15% (P < 0.01). CONCLUSION: Medical treatment
      was associated with a significantly higher overall morbidity than surgical
      therapy. Additionally, a three stage restorative proctocolectomy was performed at
      no additional hospital cost or subsequent disability in patients with severe
      ulcerative colitis. The value of prolonged medical therapy in this select group
      of patients is questionable.

PMID- 9007627
TI  - Laparoscopic intracorporeal anastomosis in the colon using the biofragmentable
      anastomotic ring--an animal study.
AB  - This experimental study examines the usefulness of a totally laparoscopic
      anastomotic technique in the colon with the aid of the biofragmentable
      anastomotic Valtrac ring and a newly developed applicator device. Following
      closed intracorporeal colonic resection with the linear stapler and subsequent re
      opening of the proximal and distal bowel ends after placement of a pursestring
      suture, intracorporeal anastomosis was completed with the Valtrac ring. The
      technique was tested in 8 pigs. 6 pigs had no intra- or postoperative
      complications, while 2 pigs developed fatal peritonitis following anastomotic
      insufficiency in one pig and anastomotic stenosis caused by tilting of the
      Valtrac ring in the other animal. The results of the study show that handling of
      the biofragmentable anastomotic ring is facilitated by the use of the new
      application system. In the uncomplicated case, endoscopy and histology revealed
      bland healing with little scarring, and no evidence of an anastomotic stenosis.

PMID- 9007626
TI  - Factors affecting recurrence in Crohn's disease. Results of a prospective audit.
AB  - It has been suggested that certain clinical and morphological features can modify
      the outcome of Crohn's disease, particularly regarding recurrence after surgery.
      A series of 233 patients was followed prospectively. They underwent a resectional
      surgical procedure for both primary and recurrent Crohn's disease during a
      fifteen-year period with a minimum follow-up of eighteen months. Possible risk
      factors for recurrence were studied. They included duration of disease before
      primary surgery, the type of clinical presentation at onset (whether
      "Perforating" or "Non-perforating"), the initial anatomical location, the
      presence of microscopic disease at the resection edges, the type of surgical
      procedure (anastomosis vs stoma), post-operative surgical complications and the
      age of the patient. The duration of the disease before the initial operation was
      the only significant factor related to the recurrence rate.

PMID- 9007628
TI  - "Is early postoperative feeding feasible in elective colon and rectal surgery?".

PMID- 9007629
TI  - Macrophage subtype patterns in protracted asphyxiation.
AB  - The question was examined whether protracted asphyxiation is associated with a
      distinct macrophage subtype pattern in lung tissue. Immunohistochemical
      preparations of lung specimens were tested with the antibodies MRP8, MRP14, 27E10
      and 25F9 in cases of protracted asphyxiation (n = 8) and in "control" groups
      (hanging: n = 6; peracute deaths: n = 9). MRP8 and MRP14 interstitial cell counts
      showed a doubling in protracted asphyxiation. Furthermore, clear increases of
      27E10 and 25F9 cells (intravascular and interstitial) were found in protracted
      asphyxiation, both in the intravascular and interstitial compartments. At present
      the results look promising as to an additional diagnostic criterion for the
      differential diagnosis between acute and protracted asphyxiation.

PMID- 9007630
TI  - Assessment of myocardial vasculature in chronic alcoholics without established
      cardiomyopathy.
AB  - Myocardial pathology and cardiac functional abnormalities known to occur in
      association with chronic alcohol abuse have been attributed to a direct toxic
      effect of ethanol on the intra-myocardial vasculature: alcohol-induced occlusion
      of small arteries with consequent secondary ischaemia leads to individual myocyte
      loss, focal fibrosis and compensatory cardiac hypertrophy. To assess the intra
      myocardial arterial vessels an interactive semiautomated, computerised, high
      resolution, video image-analysing system was used and the findings from hearts of
      alcoholics were compared with normal hearts collected at autopsy. The elastic
      laminae, stained with Van Gieson's stain, acted as the reference points for
      measurement of the diameters, circumferences and thicknesses of the vessels
      assessed. It was not possible to demonstrate any statistically significant
      morphometric changes within intra-myocardial vasculature. The same technique used
      is readily adaptable for the assessment of the blood vessels in other organs and
      tissues.

PMID- 9007631
TI  - Statistical analysis of a large file of data from STR profiles of British
      Caucasians to support forensic casework.
AB  - Data from nearly 2500 British Caucasians, profiled using an STR quadruplex, have
      been analysed. The data came from several laboratories and represent samples from
      different geographical distributions. Analysis of the combined files shows that
      previous reports of failed independence tests were the results of sampling
      effects. A further convincing proof is given of the robustness of the statistical
      methods used to estimate evidential value in casework. Comparisons between
      different samples show that regional effects between Scotland and the South of
      England have no importance from the forensic viewpoint.

PMID- 9007632
TI  - Population genetic and family data for the human minisatellite locus D16S309
      (MS205) in Germans.
AB  - The distribution of restriction fragments at the DNA minisatellite locus D16S309
      was estimated by investigating blood samples from 2617 unrelated West German
      Caucasians and 1269 offspring. Furthermore segregation of fragments was studied
      in a large family and in trios. Altogether 2296 meioses were studied, revealing 7
      paternal and 3 maternal mutations. Inspection of "phenotypes" did not reveal any
      remarkable deviation from Hardy-Weinberg equilibrium.

PMID- 9007633
TI  - HLA-DQA1 in autochthonous Basques: description of a genocline for the DQA1*0201
      allele in Europe.
AB  - A total of 250 autochthonous Basque individuals were tested in the HLA-DQA1
      system, and the allele frequency distribution found was significantly different
      from that of any other European population. The differences centre mainly on the
      alleles DQA1*0201 and DQA1*0501: for the former the Basques have the highest
      frequency described anywhere in the world (f = 0.210) and for the latter they
      have the lowest frequency in Europe (f = 0.204). For the allele DQA1*0201 a
      genocline is also described in Europe with the Basques and Finno-Ugric
      populations basically at the extremes. The genocline reflects the isolation of
      the Basque population since prehistoric times, and supports existing linguistic,
      archaeological and genetic data.

PMID- 9007634
TI  - The validation of a 7-locus multiplex STR test for use in forensic casework. (I).
      Mixtures, ageing, degradation and species studies.
AB  - We have evaluated a multiplex STR system for routine forensic use, which co
      amplifies six short tandem repeat (STR) loci; HUMTH01, D21S11, D18S51, D8S1179,
      HUMVWF31/A and HUMFIBRA (FGA), in conjunction with the X-Y homologous gene
      Amelogenin. Analysis of PCR products employs denaturing polyacrylamide gels
      coupled with fluorescent labelled primers and detection is undertaken on ABD 373A
      automated sequencers. The technique was shown to be robust and reproducible when
      samples were analysed under conditions consistent with those encountered in a
      forensic environment. The system was demonstrated to be human specific and is
      suitable for use with both aged and degraded material. Somatic stability was
      proven with a wide range of tissue types and we were able to detect mixtures at
      ratios between 1:10 and 10:1. During this study no incidence of sample mis-typing
      due to allelic or locus drop-out was observed. Furthermore, although additional
      artefact bands were occasionally encountered these did not interfere with the
      interpretation of results. The performance of the system with poor quality
      samples demonstrated its suitability as a powerful tool in forensic
      investigation.

PMID- 9007635
TI  - The validation of a 7-locus multiplex STR test for use in forensic casework.
      (II), Artefacts, casework studies and success rates.
AB  - PCR-based DNA typing of biological evidence is now widely used in forensic
      analyses due to the obvious advantages of enhanced sensitivity, the ability to
      distinguish discrete alleles and efficacy with degraded samples. A multiplex
      short tandem repeat (STR) system has been previously developed which successfully
      co-amplifies six STR loci HUMTH01, D21S11, D18S51, D8S1179, HUMVWF31/A and
      HUMFIBRA (FGA) in conjunction with the X-Y homologous gene Amelogenin. This is
      known as the second generation multiplex system (SGM). Detection of the PCR
      products is undertaken on ABD 373A or 377 automated sequencers using denaturing
      polyacrylamide gels coupled with fluorescent-based technology. We have evaluated
      this system for routine forensic use and demonstrated that the technique is
      robust and reproducible under conditions consistent with those encountered in a
      forensic environment. A total of 132 stains from simulated and actual casework
      were analysed, together with relevant control areas and reference samples. The
      success rate was high with 76% of stains giving full profiles; we were also able
      to successfully detect and interpret mixtures. No mistyping was observed. A
      detailed examination of each of these profiles has assisted in the development of
      guidelines for casework interpretation. Although artefacts, stutter peaks and
      undenatured DNA were occasionally observed, these did not interfere with the
      accuracy of interpretation. In addition 38 samples, previously examined using the
      quadruplex system, were analysed with the SGM to enable a direct comparison to be
      made between the systems. The performance of the system with poor quality samples
      demonstrated its use as a rapid and powerful technique for individual
      identification.

PMID- 9007636
TI  - mtDNA as a tool for identification of human remains. Identification using mtDNA.
AB  - Two cases are presented in order to emphasize the importance of mitochondrial DNA
      in forensic medicine. The first case involved a charred body which could not be
      identified by morphological means because of severe destruction of all tissues.
      The parallel use of PCR methods using genomic DNA and sequencing of the
      mitochondrial d-loop region produced unequivocal and reproducible results. In the
      second case, various parts of a highly decomposed body were investigated. The
      application of standard PCR methods for genomic DNA proved unsuitable to answer
      the question whether the body parts belonged to the same body. However, when
      sequencing of mitochondrial DNA segments amplified from tissue and bone samples
      was performed, clearly interpretable results were obtained.

PMID- 9007638
TI  - Analysis of fentanyl and sufentanil in hair by GC/MS/MS.
AB  - Fentanyl and sufentanil are potent narcotic analgesics used only in hospitals as
      anaesthetic agents. The dependence potential of fentanyl is known. As they are
      given in doses at the microgram level and their elimination half-life is in the
      order of a few hours, detection in body fluids is possible only for a short time
      after administration. Radioimmunological methods are the only ones capable of
      detecting fentanyl in hair, as normal GC/MS methods for hair analysis are not
      sensitive enough to detect the drugs after doses in the order of micrograms. We
      therefore chose GC/MS/MS to analyse fentanyl and sufentanil in two cases where
      the drugs were given under controlled conditions over several days. The
      concentration was in the order of less than 100 pg/mg hair.

PMID- 9007637
TI  - Differential diagnosis of postoperative liver failure in a 12-year-old child.
AB  - The case of a 12-year-old child who died of fulminant hepatic failure a few days
      after tonsillectomy is reported. Histological examination revealed large areas of
      massive centrilobular hepatic necrosis. Hepatotoxicity of postoperatively
      administered paracetamol in high dosages combined with enflurane exposure is
      discussed as a cause for the hepatic failure. The fulminant clinical course could
      have been influenced by an infection with hepatitis G virus which was detected in
      liver tissue by in situ hybridisation and was probably transmitted via
      transfusion of blood plasma.

PMID- 9007639
TI  - An improved method for MN genotyping by the polymerase chain reaction.
AB  - A novel method of human MN blood group genotyping is reported using the
      polymerase chain reaction. Genotyping is based on two base substitutions
      characteristic of M and N alleles in the 2nd exon of the glycophorin A gene.
      Using a newly designed primer trio, PCR products for M (255 bp) and N (270 bp)
      alleles are rapidly and simultaneously detected by a single PCR procedure and
      subsequent polyacrylamide gel electrophoresis. This method enables MN genotyping
      from not only minute but also degraded DNA samples.

PMID- 9007640
TI  - Likelihood ratios for mixed stains when the number of donors cannot be agreed.
AB  - Suppose that part of the prosecution's evidence in some crime case is analysis of
      a blood stain, and that the traits E discovered in the stain suggest multiple
      donors. Then the prosecution will probably allege some specific inculpatory
      hypothesis H0 about the sources of the stain, and P (E [symbol: see text] H0) can
      be calculated. It is desirable to use this as the numerator of a likelihood
      ratio. However, in general the obvious denominator P (E [symbol: see text]
      approximately H0) cannot be calculated, so unless the defense is sufficiently
      obliging as to stipulate to a specific choice among the potentially infinite
      number of more or less exculpatory alternative hypotheses, the desired likelihood
      ratio can't be evaluated. We show that nonetheless, in most cases there is an
      adequate inequality.

PMID- 9007641
TI  - Magnetic resonance imaging of the female pelvis. New circularly polarized body
      array coil versus standard body coil.
AB  - RATIONALE AND OBJECTIVES: The authors compare the value of a new circularly
      polarized body array coil (BAC) system with a standard body coil (BC) for high
      resolution magnetic resonance imaging of the female pelvis. METHODS: Twenty
      patients with cervical cancer were examined with a BC and BAC. Imaging parameters
      were kept constant (sagittal T2-weighted turbo spin-echo: repetition time = 4000
      mseconds; effective echo time = 99 mseconds; 160 x 160 mm field of view; 256 x
      256 matrix; 0.63 x 0.63 mm pixel size; 4-mm slice thickness). Images were scored
      for lesion-to-organ delineation and overall image quality/ artifacts using a
      scale from 5 to 1 (excellent to poor). Signal-to-noise (S/N) ratios for different
      tissues (tumor, uterus, vagina, rectum, muscle, and fat) as well as contrast-to
      noise (C/N) ratios between tumor and (1) uterus, (2) vagina, and (3) rectum were
      calculated. Magnetic resonance tumor staging was performed according to the
      International Federation of Gynecology and Obstetrics (FIGO) classification.
      RESULTS: Using the BAC, S/N and C/N ratios increased significantly compared with
      the BC (S/N: 2.7-3.4-fold increase for all organs evaluated, P < 0.001: C/N:
      tumor versus uterus 2.4-fold, P < 0.01; tumor versus vagina 6.1-fold, P < 0.001;
      tumor versus rectum 3.1-fold, P < 0.01). This resulted in an improved overall
      image quality (average ratings: BAC-4.3 points; BC-2.6 points; P < 0.001). Lesion
      to-organ delineation (average ratings: BAC 4.3-4.1 points, BC 3.5-2.7 points for
      all organs evaluated; P < 0.001) was increased noticeably on BAC images. No
      significant difference was found for staging accuracy. CONCLUSIONS: Circularly
      polarized BAC provide superior S/N and C/N ratios and improve lesion conspicuity
      compared with standard BC.

PMID- 9007642
TI  - Evolving stages of lipohemarthrosis of the knee. Sequential magnetic resonance
      imaging findings in cadavers with clinical correlation.
AB  - RATIONALE AND OBJECTIVES: Lipohemarthrosis, the presence of fat and blood in a
      joint cavity, exhibits several complex layers related to differences in specific
      component relaxation on magnetic resonance (MR) images. The authors investigated
      sequential changes in the appearance of lipohemarthrosis of the knee as
      demonstrated by MR imaging. METHODS: Sequential MR imaging over a 4-day period
      was performed on two cadaveric knees after intraarticular injection of blood from
      a volunteer and fat from a cadaveric tibia (50 mL of blood and 25 mL of fat in
      one knee and 15 mL of blood and 5 mL of fat in the other knee). The authors
      determined components in the joint based on MR signal behavior. Magnetic
      resonance imaging examinations of four patients with intracapsular fractures and
      lipohemarthroses of the knee were reviewed retrospectively. RESULTS: Sequential
      MR images of cadaveric knees showed serial changes representing progressive
      formation and lysis of blood clot. Several fluid-fluid levels (globules of fat at
      the interface between fat and blood) and entrapment of fat were early findings of
      lipohemarthrosis. Three different fluid levels appeared approximately 3 hours
      after injection of fresh blood and marrow fat. The 96-hour study demonstrated
      three distinct levels. CONCLUSIONS: Lipohemarthrosis demonstrates temporal
      changes on MR imaging related to stages of formation and lysis of blood clot.

PMID- 9007643
TI  - Bias and agreement for radiogrammetric estimates of cortical bone geometry.
AB  - RATIONALE AND OBJECTIVES: Radiogrammetry of the second metacarpal assumes a
      circular or elliptical model, which does not conform to reality. This study
      assesses the degree of bias and limits of agreement (error) resulting from
      deviations from these assumed models for estimates of bone mass and strength.
      METHODS: Forty-six left metacarpals were radiographed in orthogonal
      posteroanterior and mediolateral views for calculation of algebraic estimations
      of area and bending moments of area. The bones were then sectioned at midshaft
      and digitized for determination of actual values of these properties. Bias was
      determined as the mean difference between methods, and error as +/-2 standard
      deviation. RESULTS: Radiogrammetric methods significantly (P < 0.05) overestimate
      actual values for measures of cortical area and bending strength. Elliptical
      models are less biased and prone to smaller ranges of error than are uniplanar
      circular models. CONCLUSIONS: Radiogrammetric estimation of metacarpal bone mass
      is subject to considerable method error arising from use of an overly simplistic
      circular model for its midshaft geometry.

PMID- 9007644
TI  - Description and first clinical use of a new system for combined mammography and
      automated clinical amplitude/velocity reconstructive imaging breast sonography.
AB  - RATIONALE AND OBJECTIVES: The authors tested a new automated system for clinical
      amplitude/velocity reconstructive imaging (CARI) breast sonography and compared
      the results with those of a manual laboratory model of this imaging modality,
      conventional sonography, and mammography. METHODS: Fifty-one patients with breast
      lesions were examined by mammography, conventional breast sonography, a
      laboratory version of a mammography-like breast compression device for breast
      sonography, and an automated system that allows sonography while in compression
      and reconstructs an image of the whole breast. The automated device allows
      reconstruction of one image per breast from an automatically acquired sonographic
      data set and simultaneous performance of mammography. The results of mammography
      and all modes of sonography were compared with histopathology in 36 surgically
      treated lesions of which 20 were benign and 16 malignant. In addition, 17 lesions
      confirmed to be benign by different imaging modalities were examined with the
      three different sonographic devices. RESULTS: All 16 histopathologically proven
      malignant lesions were identified correctly by compression sonography (laboratory
      and automated device) compared with 14 by conventional sonography. Of the 20
      benign lesions, 16 were interpreted correctly by conventional sonography, 19 with
      the laboratory version, and 18 with the automated device, whereas mammography
      identified 12 benign lesions correctly and missed 1 malignant lesion. Only 16 of
      17 lesions diagnosed to be benign by outpatient imaging could be examined with
      all three modes of study sonography and were found to be benign with all three
      modes in all cases. CONCLUSIONS: Compared with the laboratory version, the
      automated device facilitates acquisition and evaluation of compression breast
      sonography and is similar in lesion detection and differentiation. It should be
      tested in a larger number of patients.

PMID- 9007645
TI  - Perfluorocarbon compound aerosols for delivery to the lung as potential 19F
      magnetic resonance reporters of regional pulmonary pO2.
AB  - RATIONALE AND OBJECTIVES: Perfluorocarbon (PFC) aerosols present the opportunity
      for simultaneous analysis of lung structure and pulmonary oxygenation patterns.
      The authors investigated techniques to nebulize neat liquid PFCs for inhalation
      as a new method of PFC administration and tested the hypothesis that PFC aerosols
      may be developed for efficient delivery to the lung in an experimental rat model
      allowing the potential for sequential monitoring of pulmonary status via
      quantitative fluorine-19 (19F) magnetic resonance (MR) partial pressure of oxygen
      (pO2) imaging. METHODS: Pneumatic aerosol generators were configured to produce a
      neat liquid PFC perfluorotributylamine (FC-43) aerosol. Perfluorocarbon
      inhalation breathing protocols for the rat model included: spontaneous direct
      breathing from an aerosol chamber, and use of a tracheotomy tube to bypass nasal
      breathing. The PFC aerosol delivery into the rat lung was documented through 19F
      MR imaging in correlation with high-resolution anatomic proton MR images.
      Theoretical model calculations for PFC mass deposition were compared with
      experimental results. RESULTS: The pneumatic generator produced a PFC aerosol
      droplet within the theoretically targeted range (geometric mean particle diameter
      of 1.2 microns; concentration of approximately 4 x 10(7) droplets per cm3). No
      measurable aerosol reached the lungs during spontaneous breathing because of the
      efficient filtering capabilities of the turbinated nasal passages. With
      tracheotomy, aerosol depositions within the lung were achieved in mass quantities
      consistent with theoretical expectations; however, the distribution patterns were
      nonuniform and unpredictable. Oxygen-enhanced 19F imaging was demonstrated.
      CONCLUSIONS: Perfluorocarbon aerosols of controlled size distribution can be
      produced at sufficient concentration with pneumatic generators for distribution
      to the terminal pulmonary architecture and visualization using 19F MR imaging.
      The potential exists for in vivo oxygen-sensitive imaging in the pulmonary system
      and development of sophisticated experimental animal models of systemic oxygen
      transport as a function of pulmonary status.

PMID- 9007646
TI  - 31P magnetic resonance spectroscopy detection of response-predictive adenosine
      triphosphate decrease in irradiated radiation-induced fibrosarcoma-1 tumors.
AB  - RATIONALE AND OBJECTIVES: In previous phosphorus-31 (31P) magnetic resonance (MR)
      spectroscopy studies of radiation-induced fibrosarcoma (RIF-1), tumor model
      single-dose x-ray irradiation was applied at subcurative doses. A more effective
      x-ray does was used in this study, allowing correlation of treatment efficacy
      with the early changes observed in the 31P MR spectra of RIF-1 tumors. METHODS:
      Subcutaneous RIF-1 tumors of 60 mice were examined by 31P MR spectroscopy shortly
      before a single localized x-ray dose of 40 Gy and at eight times (2, 12, 24, 48,
      72, 120, 168, and 216 hours) thereafter. RESULTS: Early increases in the relative
      concentration of inorganic phosphate and decreases in adenosine triphosphate
      (ATP), most notably at 2 and 12 hours (each P < 0.00001), were observed that
      lasted up to 48 hours after irradiation. Phosphomonoester and tumor pH showed
      decreases that reversed even earlier. Reduction of ATP measured at 48 hours after
      irradiation was, however, correlated with percent tumor shrinkage observed during
      the subsequent weeks (r = -0.59; P < 0.00001). CONCLUSIONS: Sustained loss of RIF
      1 tumor ATP is predictive of treatment efficacy. Temporary depression of high
      energy phosphate in favor of inorganic phosphate does not necessarily lead to
      cell death.

PMID- 9007647
TI  - Biodistribution and computed tomography blood-pool imaging properties of
      polyethylene glycol-coated iopromide-carrying liposomes.
AB  - RATIONALE AND OBJECTIVES: Surface-modified contrast-carrying liposomes
      potentially are useful as computed tomography (CT) blood-pool agents. The
      biodistribution and CT-imaging behavior of conventional as well as polyethylene
      glycol (PEG)-coated iopromide-carrying liposomes were tested. Two different types
      of PEG-ylated lipids were used to demonstrate possible differences. METHODS:
      Iopromide-containing liposomes were prepared by a continuous high-pressure
      extrusion method and subsequently PEG-ylated by simple mixing with either DSPE
      PEG2000 or CHHS-PEG2000. The resulting liposomes were investigated in rats
      (biodistribution) and rabbits (imaging). RESULTS: Surface modification with CHHS
      PEG consistently resulted in less effective stabilization of liposomes in the
      blood than with DSPE-PEG. In the biodistribution study, no significant
      differences in blood concentration could be found 1 hour after injection between
      the different formulations at a dose of 250 mg total iodine/kg body weight
      (approximately 500 mg lipid/kg). At this dose, the unmodified as well as the DSPE
      PEG liposomes displayed prolonged blood circulation with CT density differences
      above 70 Hounsfield units (aorta) for up to 20 minutes (n = 1). CONCLUSIONS: DSPE
      PEG-coated and unmodified liposomes proved to be useful for CT blood-pool imaging
      displaying favorable imaging properties. Future studies will have to demonstrate
      whether PEG-ylation offers diagnostic or toxicologic advantages over conventional
      vesicles in this indication.

PMID- 9007648
TI  - Quantitative analysis of the plain radiographic appearance of Brodie's abscess.
AB  - RATIONALE AND OBJECTIVES: The authors quantitate the radiographic features that
      distinguish the plain radiographic appearance of Brodie's abscess (BA) from other
      solitary lesions of bone. METHODS: Plain radiographs of 709 solitary bone lesions
      were reviewed, including 21 BAs. These were analyzed according to demographic,
      gross anatomic, and structural features. Vector analysis of groups of features
      was performed to determine those that are most sensitive and specific for the
      radiographic appearance of BA relative to other lesions of bone. RESULTS:
      Brodie's abscesses, in our series, are most commonly medullary-based (86%) lytic
      lesions (100%), with a geographic pattern of destruction (100%), well-defined
      edges (90%), marginal sclerosis (86%), and no bone enlargement (95%). In general,
      they have no periosteal reaction (71%), cortical break (95%), or visible matrix
      (90%). They typically are localized to the diaphysis or metaphysis (86%) of
      tubular bones, particularly in the lower extremity (63%). By vector analysis, the
      radiographic and demographic description of BA that provided the greatest
      sensitivity (67%-76%) while maintaining high prevalence (20%-21%) included a well
      defined lytic lesion with a geographic pattern of destruction, and no bone
      enlargement or matrix or cortical break arising in patients younger than 40 years
      old. Although BAs commonly are small lesions with maximum diameters < 50 mm, size
      criteria did not greatly affect the sensitivity or specificity for detection of
      BA in our database. The differential diagnosis generated by vector analysis
      includes osteoid osteoma, nonossifying fibroma, giant cell tumor, eosinophilic
      granuloma chondroblastoma, and fibrous dysplasia, as the major lesions.
      CONCLUSIONS: Although BA can present with a variety of radiographic features, a
      relatively specific set of radiographic characteristics can be defined to assist
      in plain-film diagnosis and to help refine the differential diagnosis of similar
      appearing lesions.

PMID- 9007649
TI  - Quantitative analysis of the plain radiographic appearance of Ewing's sarcoma of
      bone.
AB  - RATIONALE AND OBJECTIVES: The authors quantitate the radiographic features that
      distinguish the plain radiographic appearance of Ewing's sarcoma (ES) from other
      solitary lesions of bone. METHODS: A total of 709 cases of focal bone lesions,
      including 44 ES, were analyzed according to demographic, anatomic, and plain
      radiographic features. Vector analysis of groups of features was performed to
      determine those that are most sensitive and specific for the appearance of ES in
      contrast with other lesions in the database. RESULTS: In our sample, Ewing's
      sarcoma is most consistently a medullary-based (91%) lytic (89%) lesion with at
      least a partially permeative appearance (82%), poorly defined edges (82%), no
      margination (91%), and a soft-tissue mass (61%). When these lesions occur in long
      bones, they most commonly are found in the diaphysis (75%) and are proximal more
      often than distal. Vector analysis suggests that any primary bone lesion without
      radiographically visible matrix and with either a soft-tissue mass, an appearance
      of permeative destruction alone or in combination with other patterns of bone
      destruction is suspect for the diagnosis. This small subset of common features
      appears to have a high sensitivity (89%) and prevalence (47%) of ES among the
      lesions meeting these criteria. Limiting the age of the patients to progressively
      younger age groups increases the specificity but lowers sensitivity. The vector
      analysis-generated differential diagnoses includes osteosarcoma, giant-cell
      tumor, lymphoma, and chondrosarcoma. CONCLUSIONS: A relatively specific set of
      radiographic features can be defined, which will assist in the radiographic
      diagnosis of ES and improve upon current textbook descriptions.

PMID- 9007650
TI  - Ultrasound bone velocity on proximal phalanges in premenopausal, perimenopausal,
      and postmenopausal healthy women.
AB  - RATIONALE AND OBJECTIVES: The authors studied premenopausal, perimenopausal, and
      postmenopausal women to determine if ultrasound bone velocity (UBV) on proximal
      phalanges of women reflect bone changes related to gonadal status and age.
      METHODS: A total of 166 healthy women-64 postmenopausal women (mean age 58.7 +/-
      9.4 years), 41 perimenopausal women (mean age 49.5 +/- 2.9 years), and 61
      premenopausal women (mean age 36.8 +/- 7.1 years)-were studied. All the women
      underwent UBV study of the 2nd to 5th proximal phalanges on the nondominant hand
      and the mean value of all ultrasound measurements was calculated. RESULTS: The
      postmenopausal women had a UBV that differed significantly, one-way analysis of
      variance, from that of the perimenopausal women and premenopausal women (both P <
      0.001). The UBV measurements of the perimenopausal women differed significantly
      from those of the premenopausal women (P < 0.01). Simple linear regression
      analysis of the relation between UBV and age showed that this was significant and
      negative in the overall group of women (r = -0.69; P < 0.0001), significant in
      the perimenopausal (r = -0.66; P < 0.001) and postmenopausal women (r = -0.69; P
      < 0.001) and nonsignificant in the premenopausal women (r = 0.08; P not
      significant). In the postmenopausal women, the correlation between UBV and years
      since menopause was larger (r = -0.71; P < 0.0001) than the correlation between
      UBV and chronological age. CONCLUSIONS: Ultrasound bone velocity of the phalanx,
      as a method for measuring changes in bone with age, has a precision that makes it
      possible to detect changes in bone mass in perimenopausal women and may perform
      similarly to other bone mass measurements.

PMID- 9007651
TI  - A health hazard for female adolescent farmers: scalp avulsion.

PMID- 9007652
TI  - Urine-based diagnosis of sexually transmitted infections using amplified DNA
      techniques: a shift in paradigms?

PMID- 9007653
TI  - Genital Chlamydia infections in sexually active female adolescents: do we really
      need to screen everyone?
AB  - PURPOSE: To evaluate current Chlamydia trachomatis screening guidelines, which
      recommend that all sexually active female adolescents undergoing a pelvic
      examination be tested for chlamydial infection, and determine if instead
      providers should target particular subpopulations of these adolescents. METHODS:
      Data were collected from 148,650 sexually active females, ages 15-19 years,
      tested by direct immunofluorescent antibody in 160 family planning clinics from
      1988-92. Trends in chlamydia prevalence by demographic, behavioral, and clinical
      risk factors were analyzed. Logistic regression modeling was used to identify
      selective screening criteria. Predictive models were developed for all years
      combined, as well as for the years when prevalence was highest and lowest.
      RESULTS: The prevalence of C. trachomatis in this population was 10%, with a 42%
      decrease (13.2-7.6%) over the 5-year period. Logistic regression identified nine
      demographic, behavioral, and clinical predictors (p < 0.0001) associated with
      chlamydial infections. Predictor models from the highest and lowest prevalence
      years varied little from the combined model. Individual year predictor models
      showed poor sensitivity and were similar for these 2 years. The screening
      criteria could not identify a group of adolescents with a prevalence less than
      6%. CONCLUSIONS: Several individual risk factors were strongly associated with C.
      trachomatis, but no single risk factor or combination of risk factors used for
      selective screening could identify more than 42% of infections in our population.
      These findings support earlier national recommendations and the need for
      universal screening of sexually active female adolescents.

PMID- 9007655
TI  - Estimated dietary calcium intake and food sources for adolescent females: 1980
      92.
AB  - PURPOSE: To estimate dietary calcium intake of three groups of adolescent females
      ages 11-12 years, 13-14 years, and 15-18 years during four separate 2-year time
      periods from the years 1980-92; and to identify their food sources of calcium.
      METHODS: Nutrient intake survey based on 14-day food consumption records
      collected from four national representative samples of 4,000 United States
      households. RESULTS: Dietary calcium consumption declined significantly (p < .01)
      over the 10-year period for the 15-18 year olds. Calcium intake was significantly
      lower for 13-14 year olds compared to the youngest age group, and for 15-18 year
      olds when compared to the two younger age groups for all four study periods (p <
      .01). Over 90% of all adolescent females consumed < 100% of the RDA for calcium
      during all data collection periods. The percentage of adolescent females who
      consumed less than two-thirds of the RDA increased with age. Seventy-seven
      percent of 15-18 year olds consumed below this level from 1990-92. Milk and milk
      products were the best food sources of calcium contributing over one-half of the
      calcium to the diet. This percentage declined over time and with age to 44% for
      the 15-18 year old females in 1990. This drop can be attributed to a 7-12%
      decline in fluid milk consumption for the 11-12 year olds and 15-18 year olds,
      respectively. CONCLUSIONS: Estimates indicate that dietary calcium intakes fall
      far short of both the Recommended Dietary Allowance (RDA) and National Institutes
      of Health (NIH) recommendations. Intakes have declined over time, with age, and
      appear to be related to a decline in fluid milk consumption. Efforts to increase
      calcium consumption among adolescent females appear critical. Clear
      recommendations to consume a minimum of three servings everyday of lowfat or
      nonfat dairy products such as milk and yogurt are needed to help this population
      meet daily calcium requirements.

PMID- 9007654
TI  - Predicting contraceptive vigilance in adolescent females: a projective method for
      assessing ego development.
AB  - PURPOSE: To test the hypothesis that ego development would predict contraceptive
      use. Problems in ego development were defined in terms of three factors: (1)
      realism, (2) complexity, and (3) discontinuity. METHODS: Forty-one respondents
      aged 14-17 years were selected from a group of 233 adolescents who were
      administered a projective pregnancy scenario and participated in a 12-month
      follow-up. Twenty of these adolescents were randomly selected from the group
      determined to be effective contraceptive users, while 21 were randomly selected
      from the group of poor contraceptors. RESULTS: Chi-square test revealed a
      significant association (p < .0005) between the composite ego maturity (EM)
      measure and contraceptive outcome (chi 2 = 13.82, with df-1). Low scores on the
      ego maturity measure predicted poor contraceptive use. EM was unrelated to age
      but was associated with race (chi 2 = 7.535, .025 < p < .05). However, EM
      predicted contraceptive use when controlling for the effects of race.
      CONCLUSIONS: A simple, time-efficient projective pregnancy scenario is an
      effective way of determining adolescent females at risk for poor contraceptive
      effectiveness and, therefore, untimely pregnancy. These stories are analyzed
      using factors related to the ego development of the adolescent. Subjects who
      scored lower on this measure have poor contraceptive effectiveness while subjects
      with higher levels demonstrated effective contraception use, at 1-year follow-up.

PMID- 9007656
TI  - A longitudinal study of the dietary practices of black and white girls 9 and 10
      years old at enrollment: the NHLBI Growth and Health Study.
AB  - PURPOSE: To determine whether there are racial differences in the frequency with
      which black and white girls engaged in eating practices commonly targeted for
      modification in weight reduction programs. METHODS: This is part of the NHLBI
      Growth and Health Study, a longitudinal study of preadolescent girls designed to
      examine the factors associated with development of obesity, and its later effects
      on cardiovascular risk factors. Black and white girls ages 9-10 years at entry (n
      = 2,379) were recruited at three clinical sites. Racial differences were examined
      in 11 "weight-related" eating practices such as eating with TV, eating while
      doing homework, and skipping meals. Multiple logistic regression analyses were
      then conducted for each of the dependent variables. RESULTS: Black girls were
      more than twice as likely as white girls to frequently engage in the targeted
      weight-related eating practices. The odds of a study girl frequently engaging in
      most of these eating practices decreased with an increase in parents' income and
      education level. However, even when controlling for socioeconomic and demographic
      effects, black girls remained more likely to engage in these eating practices
      than white girls. For most of the behaviors, girls who frequently practiced a
      behavior had higher energy intakes compared to those who practiced it
      infrequently. CONCLUSIONS: The finding that black girls at an early age more
      frequently engage in eating practices associated with weight gain may have
      significant implications for obesity development. For both young black and white
      girls, early education efforts may be necessary in helping develop good eating
      habits. Since it appears that black girls have a higher risk of developing
      adverse weight-related eating practices, culturally appropriate education
      materials may be required.

PMID- 9007657
TI  - Risky behavior and risk in adolescents with IDDM.
AB  - PURPOSE: To determine: (1) the frequency of risky behaviors (alcohol and other
      drug use, smoking cigarettes, smokeless tobacco use, and unprotected
      intercourse); (2) the perception of general risks and diabetes-related risks from
      risky behaviors; (3) if perception of risk is related to engaging in risky
      behaviors; and (4) if perception of general risks and diabetes-related risks are
      influenced by age, gender, or race in adolescents with insulin dependent diabetes
      mellitus (IDDM). Decreasing risky behaviors in youth with IDDM is important
      because of their increased vulnerability to specific disease related physiologic
      and pathologic changes. METHODS: A descriptive, cross-sectional design was used.
      Data on risky behavior and perception of risk were obtained by self-report during
      a regularly scheduled clinic visit. One hundred and fifty-five adolescents
      between ages of 10-20 years participated. Correlational and student's t-test
      analyses were used to test relationships and group differences (age, race,
      gender). RESULTS: Thirty-nine percent of the sample reported alcohol use, 34%
      reported smoking cigarettes, 8% reported smokeless tobacco use, 10% reported drug
      use, and 29% reported unprotected intercourse. Perception of risk to peers from
      these behaviors was significantly higher (t = 8.1, df 153; p < .001) than risk to
      self. Females reported significantly lower (t = 3.08, df 52; p < .002) risk to
      self than males. There was no difference in perception of risk between youth who
      reported participating in risky behaviors (N = 38%) and those who did not (62%).
      Not surprisingly, the frequency of risky behavior increased with age (F = 15.46;
      p < .001). CONCLUSIONS: Compared to community samples of middle school children,
      our sample had lower rates for most risky behaviors. As with community samples,
      the physical risks were known and perceived to be higher for peers than self.
      Perception of risk was not related to self-reports of risky behaviors. The lower
      rate of risky behaviors might reflect the success of educational efforts directed
      toward diabetes management or may be due to later initiation of behaviors,
      especially if personal social development is delayed. Additional research is
      indicated in order to understand the timing and trajectory of risky behavior and
      whether or not perception of risk deters youth with IDDM from engaging in risky
      behavior.

PMID- 9007658
TI  - Sociobehavioral influences on smoking initiation of Hispanic adolescents.
AB  - PURPOSE: To study the sociobehavioral influences on smoking initiation of
      Hispanic adolescents over a 3-year period using a national sample. METHODS:
      Hispanic adolescents (N = 385), ages 15-22 years, from the 1989 and 1993 Teenage
      Attitudes and Practices Surveys (TAPS I and II), were selected for analyses. Data
      collected included measures of smoking initiation and attitudes, beliefs toward
      smoking of the adolescent, and smoking status of family and peers. RESULTS: At
      the 3-year follow up, 43.4% of nonsmokers at TAPS I had initiated smoking. Risk
      factors associated with initiating smoking were having male and/or female friends
      who smoked, and positive attitudes and beliefs towards smoking. Parental and
      sibling smoking status had little effect on adolescent smoking status.
      CONCLUSIONS: The peer influence on Hispanic adolescent smoking is consistent with
      previous research on Caucasian and African-American adolescents. The formation of
      attitudes and beliefs toward smoking in this population warrants further
      examination given the influence of attitudes and beliefs on smoking initiation in
      this study.

PMID- 9007659
TI  - Daughter and mother report of individual symptoms on the Children's Depression
      Inventory.
AB  - PURPOSE: To examine differences between early adolescent girls' and their
      mothers' perceptions of girls' depressive symptoms. METHODS: 313 daughter-mother
      dyads completed the Children's Depression Inventory. RESULTS: Low to modest
      agreement was found for most symptoms, although higher agreement was found for
      symptoms relating to school performance. The hypothesis that girls would report
      more ideational symptoms and mothers more behavioral symptoms of depression was
      tested; girls generally reported more ideational and behavioral symptoms when
      differences occurred. However, several specific ideational symptoms (feeling like
      crying; feeling sad; guilt; worrying) tended to be more frequently endorsed by
      girls and had particularly poor daughter-mother agreement. Examining third
      variables associated with daughter-mother agreement, girls scoring high on social
      desirability tended to have smaller daughter-minus-mother difference scores for
      ideational, but not for behavioral items; therefore, social desirability may be
      associated with girls underreporting ideational symptoms. CONCLUSIONS: Mothers
      appear to be reliable raters of symptoms related to school functioning, but may
      be less aware of certain covert depressive symptoms in their early adolescent
      daughters.

PMID- 9007660
TI  - Vitamin B12 deficiency and subclinical infection with Giardia lamblia in an
      adolescent with agammaglobulinemia of Bruton.

PMID- 9007661
TI  - Sexual behavior among adolescents reporting chronic conditions: a French national
      survey.
AB  - PURPOSE: To compare sexual behavior in adolescents with a physical handicap or a
      chronic illness (HCI, n = 604) to a healthy group (HG, n = 7,332). METHODS: Data
      drawn from a French national health survey carried out among 7,936 adolescents
      (mean age = 16.2 years) were used. A self-report questionnaire concerning health
      behavior, sexual behavior, and chronic illness was used in 136 public secondary
      schools. HCI and HG groups were compared on reported sexual behavior as well as
      on information (on sexuality, AIDS, and pregnancy) given by the parents. Logistic
      regression was performed for boys and girls to explore the relationship of health
      status (HCI or HG) to sexual intercourse, adjusted for sociodemographic
      variables. RESULTS: Fifty-two percent of HCI boys and 38% of HCI girls reported
      sexual intercourse (vs. 42% of HG boys and 28% of HG girls). The HCI girls
      reported more often than HG girls changing partners, pregnancy, and use of oral
      contraceptives. The HCI boys reported more often than HG boys receiving
      information on sexuality from their parents. CONCLUSIONS: French HCI adolescents
      were found to be at high risk for pregnancy and sexually transmitted diseases
      (STD).

PMID- 9007662
TI  - Human immunodeficiency virus risk behavior among white and Asian/Pacific Islander
      high school students in the United States: does culture make a difference?
AB  - PURPOSE: This article analyzes sexual behavior among white and Asian/Pacific
      Islander (API) adolescents, to determine the risk for human immunodeficiency
      virus (HIV) transmission from a multicultural point of view. METHODS: A total of
      5,385 white and 408 API high school students were included. The national school
      based Youth Risk Behavior Survey (YRBS 1991) was used. RESULTS: After controlling
      for academic performance, white students were 2.3 times more likely to
      communicate about acquired immunodeficiency syndrome (AIDS)/HIV, 2.7 times more
      likely to be sexually experienced, and 2.5 times more likely to use alcohol or
      other drugs before sex than APIs. There were no significant differences between
      these two groups in the age of initiating sex, the number of lifetime partners,
      the proportion of being currently sexually active (having had sex during the past
      3 months), and condom use behavior. Although APIs had a low rate of AIDS/HIV,
      they have behaviors at as high a risk as white students once they became sexually
      experienced, and they have an even greater number of recent partners if they are
      currently sexually active. Use of alcohol or other drugs before sex and condom
      use is significantly related. CONCLUSIONS: Given the importance of attention to
      risks among API adolescents, this study underscores the need for more research to
      explore how culture values play a role among all API students, those who are
      sexually experienced, and those who are currently sexually active API students,
      to develop culturally sensitive AIDS/HIV prevention programs.

PMID- 9007663
TI  - Differential effects of arginine vasopressin on isolated guinea pig heart
      function during perfusion at constant flow and constant pressure.
AB  - 8-Arginine vasopressin (AVP) is a powerful coronary vasoconstrictor as well as
      peripheral vasoconstrictor, but AVP also is reported to have negative cardiac
      inotropic and chronotropic effects in vitro and in vivo. Our aim was to examine
      the direct effects of coronary vasoconstriction by AVP on cardiac function and
      metabolism in isolated guinea pig hearts perfused either at a constant perfusion
      pressure (CPP) of 55 mm Hg or at a constant coronary flow (CCF) equal to the
      initial natural flow at constant pressure. Coronary vasoconstriction was elicited
      by perfusing hearts with increasing concentrations of AVP in random order.
      Variables assessed were atrial heart rate (HR), atrioventricular (AV) conduction
      time, left ventricular pressure (LVP), coronary flow, inflow and outflow O2
      tensions, O2 delivery (Do2), oxygen consumption (MVo2), percentage oxygen
      extraction (%O2E) and cardiac efficiency (HR-LVP/MVo2). We found that AVP
      increased coronary vascular resistance more at CCF than at CPP. The decrease in
      coronary flow, as a function of AVP at CPP, produced concentration-dependent
      decreases in heart rate, LVP, and MVo2, a decrease in Do2/MVo2, increases in AV
      conduction time and %O2E, and no significant change in cardiac efficiency. In
      contrast, the increase in perfusion pressure as a function of AVP at CCF caused
      no change in HR and AV conduction time, much smaller decreases in LVP and
      Do2/MVo2, a smaller increase in %O2E, an increase rather than a decrease in MVo2,
      and a decrease in cardiac efficiency. Our results indicate that larger decreases
      in HR, LVP, MVo2, and Do2/MVo2, and the larger increases in AV conduction time
      and %O2E with the AVP-induced decrease in CF at CPP are consistent with
      myocardial depression resulting from reduced global perfusion. However, cardiac
      efficiency was maintained at CPP because the decreased HR and LVP product
      (cardiac work) matched the decrease in MVo2. At CCF, AVP did not directly produce
      myocardial depression, but the small time-dependent decrease in LVP over time was
      not matched by the increase in MVo2, so that cardiac efficiency was not
      maintained. The demonstration of an increase in MVo2 despite no change or a
      decrease in cardiac work by coronary vasoconstriction with AVP at CCF, but not at
      CPP, suggests that cardiac O2 use is dependent more on maintenance of CF, despite
      increased resistance to perfusion, rather than on maintenance of perfusion
      pressure. Our data agree that Gregg's phenomenon results from a hydraulic effect
      to distend coronary vasculature because when flow is not allowed to decrease
      during vasoconstriction, MVo2 increases even though HR is unchanged and LVP is
      slightly decreased. This is supported by the finding that AVP does not increase
      coronary vascular resistance during CCF as much as during CPP, so that O2 supply
      is better maintained to match MVo2.

PMID- 9007664
TI  - Acute amelioration of diabetic endothelial dysfunction with a derivative of the
      nitric oxide synthase cofactor, tetrahydrobiopterin.
AB  - Tetrahydrobiopterin is a cofactor for nitric oxide synthase. In low
      concentrations of this cofactor, nitric oxide synthase is known to produce less
      nitric oxide and, correspondingly, enhanced quantities of the oxidant species,
      hydrogen peroxide. In this study, we tested the hypothesis that an exogenous
      tetrahydrobiopterin derivative might improve endothelial nitric oxide synthase
      activity in diabetic endothelium. Diabetes was induced in Sprague-Dawley rats
      with intravenous injections of streptozotocin. After 8 weeks, endothelium
      dependent relaxation was assessed in aortic rings by using acetylcholine, whereas
      endothelium-independent relaxation was assessed by using nitroglycerin.
      Acetylcholine-induced relaxation was impaired in diabetic rings, whereas
      nitroglycerin-induced relaxation was unimpaired. Exposure of rings for 30 min
      with 100 microM of the pteridine derivative, 6-methyl-5,6,7,8-tetrahydropterin
      (in the presence of diethylenetriaminepentaacetic acid to inhibit oxidation),
      followed by washing and equilibration in control media, augmented relaxation
      induced by acetylcholine in diabetic rings but had no effect on relaxation in
      control rings. Pteridine exposure did not alter relaxation or sensitivity to
      nitroglycerin in control rings either with or without endothelium. In diabetic
      rings, pteridine exposure augmented maximal relaxation to nitroglycerin in rings
      with or without endothelium while increasing the sensitivity only in rings with
      endothelium but not in rings without endothelium. In contrast, there was no
      effect of pteridine exposure on relaxation or sensitivity to nitroglycerin in
      diabetic rings (with or without endothelium) that are pretreated with L
      nitroarginine. In summary, tetrahydrobiopterin availability can play a key role
      in the regulation of nitric oxide production by diabetic endothelium.

PMID- 9007665
TI  - Dietary coenzyme Q10 supplementation alters platelet size and inhibits human
      vitronectin (CD51/CD61) receptor expression.
AB  - Improved cardiovascular morbidity and mortality have been observed in several
      clinical studies of dietary supplementation with coenzyme Q10 (CoQ10,
      ubiquinone). Several mechanisms have been proposed to explain the effects of
      CoQ10, but a comprehensive explanation of its cardioprotective properties is
      still lacking. One attractive theory links ubiquinone with the inhibition of
      platelets. The effect of CoQ10 intake on platelet size and surface antigens was
      examined in human volunteers. Study participants received 100 mg of CoQ10 twice
      daily in addition to their usual diet for 20 days. Receptor expression was
      measured by flow cytometry with monoclonal murine anti-human antibodies CD9
      (p24), CD42B (Ib), CD41b (IIb), CD61 (IIIa), CD41a (IIb/IIIa), CD49b (VLA-2),
      CD62p (P selectin), CD31 (PECAM-1), and CD51/CD61 (vitronectin). An increase of
      total serum CoQ10 level (from 0.6 +/- 0.1 to 1.8 +/- 0.3 micrograms/ml; p <
      0.001) was found at protocol termination. Fluorescence intensity was higher for
      the large platelets when compared with the whole platelet population. Significant
      inhibition of vitronectin-receptor expression was observed consistently
      throughout ubiquinone treatment. Reduction of platelet size was observed at the
      end of CoQ10 supplementation. Inhibition of the platelet vitronectin receptor and
      a reduction of the platelet size are direct evidence of a link between dietary
      CoQ10 intake and platelets. These findings may not be fully explained by the
      known antioxidant and bioenergetic properties of CoQ10. Diminished vitronectin
      receptor expression and reduced platelet size resulting from CoQ10 therapy may
      contribute to the observed clinical benefits in patients with cardiovascular
      diseases.

PMID- 9007666
TI  - Effect of methylprednisolone on complement activation during heparin
      neutralization.
AB  - During cardiac surgery, steroids are frequently administered before the
      initiation of cardiopulmonary bypass (CPB), termed "pre-treatment," to reduce
      "first phase" complement activation during cardiopulmonary bypass (CPB). "Second
      phase" complement activation also occurs during heparin neutralization with
      protamine, although the effects of steroid pretreatment on such activation are
      unknown. This study was performed in patients undergoing coronary artery bypass
      graft surgery to determine whether high-dose methylprednisolone pretreatment
      affected complement activation during heparin-protamine interaction after
      termination of CPB. In eight patients (group MP), methylprednisolone, 30 mg/kg,
      was administered before CPB commencement, whereas another eight patients received
      placebo (group C). By using 125I des Arg radioimmunoassay, C3a, C4a, and C5a were
      measured in the arterial blood samples drawn before and 10 min after
      administration of protamine. An increase in C3a and C4a was observed in both
      groups after protamine, suggesting classic pathway activation (delta C3a: group
      C, 4,484 +/- 3,320; group MP, 1,394 +/- 1,653; delta C4a: group C, 1,810 +/- 731;
      group MP, 717 +/- 580). C3a and C4a levels were significantly lower in group MP
      patients after protamine compared with controls [delta C3a, 3,499 +/- 1,826 (p <
      0.05); delta C4a, 1,241 +/- 232 (p < 0.05)]. C5a was not detected in any samples.
      These results demonstrate that the effect of pretreatment persists beyond the
      period of CPB and that methylprednisolone inhibits second-phase complement
      activation during heparin-protamine interaction. These findings have implication
      for patients with severe anaphylactoid reactions to protamine.

PMID- 9007667
TI  - Glyburide-reversible cardioprotective effects of BMS-180448: functional and
      energetic considerations.
AB  - Adenosine triphosphate (ATP)-sensitive potassium channel openers as a class exert
      cardioprotective effects, and we can separate vasodilator from glyburide
      reversible cardioprotective activity in cromakalim analogs (e.g., BMS-180448).
      The purpose of this study was to determine the relation between cardiac function,
      energy status, and cardioprotective effects for BMS-180448 in isolated rat hearts
      compared with diltiazem. BMS-180448 (1-30 microM) or 0.1-1 microM diltiazem were
      given 10 min before 25-min global ischemia in rat hearts followed by 30 min of
      reperfusion. Both compounds significantly increased time to the onset of
      contracture during ischemia and improved postischemic recovery of contractile
      function in a concentration-dependent manner. At equivalent cardioprotective
      concentrations, BMS-180448 depressed preischemic cardiac function significantly
      less than did diltiazem. During ischemia, diltiazem significantly accelerated the
      functional decline observed in vehicle-treated hearts, whereas BMS-180448
      attenuated the net rate of decline of function. Despite these different effects
      on preischemic and ischemic cardiac function, diltiazem and BMS-180448 conserved
      cardiac ATP during ischemia to a similar degree. BMS-180448 enhanced the recovery
      of ATP (also seen for diltiazem, but not to the same magnitude) and creatine
      phosphate during reperfusion compared with vehicle-treated hearts. For BMS
      180448, this enhanced ATP recovery was accompanied by a significant improvement
      in the efficiency of oxygen use, which was profoundly reduced in reperfused
      vehicle-treated hearts. BMS-180448 also significantly enhanced the functional
      reserve after the 25-min period of global ischemia. Thus BMS-180448 protects
      ischemic myocardium and conserves ATP with less reduction in cardiac function
      compared with diltiazem.

PMID- 9007668
TI  - Electrophysiologic characteristics of a pulsed iontophoretic drug-delivery system
      in coronary arteries.
AB  - This study evaluated the electrophysiologic effects of a pulsed iontophoretic
      drug-delivery system when used in the coronary arteries. Prevention of acute
      thrombosis and restenosis after intravascular procedures may be enhanced by high
      concentrations of therapeutic agents within the vessel wall. A new intravascular
      drug-delivery system uses iontophoresis to maximize local tissue concentrations
      of drug. However, the electrophysiologic effects of such a system in coronary
      arteries are unknown. An iontophoretic membrane balloon-tipped catheter was
      placed fluoroscopically in the mid left anterior descending coronary artery of 10
      anesthetized dogs. Strength-duration curves and effective refractory period (ERP)
      were initially determined. Threshold for capture was assessed at pulse widths of
      0.5, 1.0, 2.0, 4.0, and 8.0 ms. Capture occurred at 4.9 +/- 0.9, 3.4 +/- 0.5, 2.6
      +/- 0.5, 1.6 +/- 0.2, and 1.2 +/- 0.2 mA, respectively. The ERP was 169 +/- 6 ms
      (4.0-ms pulses at twice threshold). Then square-wave pulses for iontophoresis
      were R-wave synchronized and delivered at 50 and 75% of the ERP with the balloon
      inflated to 1 atm. Output was increased until significant arrhythmias occurred
      [premature beats > 10/min, supraventricular tachycardia (SVT), ventricular
      tachycardia (VT), ventricular fibrillation (VF)], by using sequential steps of 1,
      5, 10, 15, and 20 mA. Highest average outputs achieved without an arrhythmia were
      14.1 +/- 2.5 and 4.9 +/- 2.0 mA at 50 and 75% of ERP, respectively (p < 0.05).
      High-grade arrhythmias (pulseless VT or VF) occurred in three of four animals
      studied before use of a frequency limiter, which allowed current delivery only at
      intervals > 400 ms (thus inhibiting current activation during premature beats).
      No further VT or VF occurred in the remaining six animals, except for one episode
      of nonsustained VT (11 beats). An R-wave synchronized iontophoretic field with a
      response-frequency limiter can be safely used within the canine coronary arterial
      system at 50% of ERP with moderate outputs (5-10 mA). Increasing the stimulus
      duration to 75% of ERP increases arrhythmogenesis but is tolerated at lower
      output levels (< 5 mA).

PMID- 9007669
TI  - Dissociation between the increase in systemic vascular resistance induced by
      acute nitric oxide synthesis inhibition and the decrease in cardiac output in
      anesthetized dogs.
AB  - The decrease in cardiac output (CO) that follows nitric oxide (NO) synthesis
      inhibition is thought to be the result of an increase in systemic vascular
      resistance (SVR). We investigated whether sodium nitroprusside (SNP) and iloprost
      prevent the decrease in CO induced by short-term administration of N omega-nitro
      L-arginine methyl ester (L-NAME) in anesthetized dogs. The left femoral artery
      and vein were cannulated for mean arterial blood pressure (MABP) measurement and
      drug administration, respectively. A Swan-Ganz thermodilution catheter was
      inserted into the right femoral vein and allowed the determination of CO and the
      calculation of SVR, expressed as the cardiac index (CI) and the index of systemic
      vascular resistance (ISVR), respectively. L-NAME (0.01-10.0 mg/kg; n = 13)
      induced dose-dependent increases in MABP and in the ISVR. These changes were
      accompanied by significant decreases in both the CI and the heart rate. SNP (1
      microgram/kg/min; n = 6) virtually abolished L-NAME-induced hypertension and
      significantly attenuated both the increase in the ISVR (< 3.0 mg/kg) and the
      decrease in CO. Iloprost (50 ng/kg/min; n = 6) also abolished L-NAME-induced
      hypertension and markedly attenuated the increase in SVR. However, the decrease
      in CO was not prevented by this vasodilator. These results clearly demonstrate
      that the increase in SVR is not the major factor accounting for the decrease in
      CO after short-term NO synthesis inhibition in anesthetized dogs.

PMID- 9007670
TI  - Regional hemodynamic dose-response of lemakalim and glybenclamide in anesthetized
      rats.
AB  - Studies were undertaken to establish the regional hemodynamic profile and dose
      response relation of the adenosine triphosphate (ATP)-dependent potassium channel
      activator lemakalim in anesthetized rats. In addition, the ability of the
      sulphonylurea potassium channel blocker glybenclamide to reverse the hemodynamic
      effects of an infusion of lemakalim was determined. Studies were performed in
      anesthetized rats instrumented to measure arterial pressure, heart rate, and
      hemodynamics in the coronary, mesenteric, renal, and hindquarters vascular beds.
      One group of rats (n = 5) received increasing intravenous infusion rates of the
      potassium channel activator lemakalim. The doses administered were 0.1, 0.3, 1.0,
      3.0, and 10 micrograms/kg/min, and each dose was infused until steady
      stateresponses were achieved. Dose-related decreases in mean arterial pressure
      were observed with the first significant effect occurring at 1 microgram/kg/min.
      The hindquarters bed was the most sensitive of the four beds measured. Vascular
      resistance was significantly decreased in this bed with an infusion of 0.3
      microgram/kg/min i.v. lemakalim. In addition, this vascular bed was the only one
      to demonstrate significant increases in blood flow over baseline. Significant
      reductions in vascular resistance were observed over the dose range of 1-10
      micrograms/kg/min for both the coronary and renal vascular beds. The mesenteric
      bed was less sensitive in that the first significant reduction in resistance was
      not observed until the infusion dose was increased to 3 micrograms/kg/min. The
      other group of rats (n = 5) was used to determine the dose-response relation of
      glybenclamide. These rats received an intravenous infusion of lemakalim at 1
      microgram/kg/min to establish a moderate cardiovascular effect. Ascending
      cumulative intravenous injections of glybenclamide from 0.3 to 30 mg/kg were then
      administered. The lowest dose, 0.3 mg/kg, significantly attenuated the depressor
      response to the lemakalim infusion, but the response was not fully reversed until
      the dose of glybenclamide reached 10 mg/kg i.v.. Doses > 10 mg/kg i.v. of
      glybenclamide were required for complete reversal of the hemodynamic responses to
      this dose of lemakalim. Therefore lemakalim exerts vasodilatory properties in
      each of the beds measured but demonstrates a selectivity for the hindquarters.
      The results with glybenclamide demonstrate also that the responses to lemakalim
      are the result of activation of the ATP-dependent potassium channel. Last, doses
      > 10 mg/kg of glybenclamide are required to ensure that ATP-dependent potassium
      channels are blocked in the circulatory system in rats.

PMID- 9007671
TI  - Alpha 1D-adrenoceptors do not contribute to inotropic responses of neonatal rat
      myocardium.
AB  - This study investigated the role of alpha 1D-adrenoceptors (ARs) in the inotropic
      responses of neonatal (7-day-old) rat myocardium by using the relatively
      selective antagonist BMY 7378. The positive inotropic effects of phenylephrine on
      right ventricular strips of neonatal rats were not inhibited by BMY 7378 up to a
      concentration of 300 nM but potently antagonized by the alpha 1AAR antagonist 5
      methylurapidil (5-MU) (pKB, 8.73 +/- 0.12; n = 6). BMY 7378 was approximately
      1,000-fold less potent (pKi, 6.63 +/- 0.7; n = 5) in inhibiting the binding of
      [3H]prazosin to right ventricular membrane preparations of neonatal rats than was
      5-MU (pKi, 9.04 +/- 0.54; n = 5). Neonatal rat cerebral cortex and adult rat
      aorta were used as additional controls. BMY 7378 was a weak inhibitor of
      [3H]prazosin binding to neonatal cortex (pKi, 6.8 +/- 0.04; n = 3) but highly
      potent in inhibiting the binding to adult rat aortic membrane preparations (pKi
      for high-affinity binding, 9.70 +/- 0.30; n = 4); BMY 7378 potently antagonized
      the effects of phenyleprine on adult rat aortic strips (pKB, 9.05 +/- 0.11; n =
      5). It is concluded that alpha 1DARs do not play a significant role in alpha 1AR
      mediated inotropic responses of neonatal rat myocardium.

PMID- 9007672
TI  - Hypertonic saline does not reverse the sodium channel blocking actions of
      lidocaine: evidence from electrophysiologic and defibrillation studies.
AB  - Studies have shown that increasing extracellular sodium concentration can
      partially reverse sodium channel blockade. However, there is conflicting in vitro
      evidence in this regard for lidocaine. The effects of lidocaine on cardiac
      electrophysiology and defibrillation were studied in a basal and hypernatremic
      state to determine reversibility of sodium channel blockade. Electrophysiologic
      studies measured right ventricular effective refractory period at 350 ms pacing
      cycle length and QRS interval, JT interval, and monophasic action potential
      duration during sinus rhythm and right ventricular pacing (350 ms cycle length)
      in 14 pentobarbital-anesthetized swine (25-30 kg). Defibrillation threshold (DFT)
      was measured by quantitating successful conversion of sustained ventricular
      fibrillation to normal sinus rhythm. Each pig was randomly assigned to a
      treatment group with three study phases; group 1 = baseline, lidocaine (20
      mg/kg/h), and lidocaine plus placebo (D5W; n = 7); and group 2 = baseline,
      lidocaine, and lidocaine plus hypertonic saline (2-3 mM/kg/h; n = 7). In groups 1
      and 2, lidocaine infused alone significantly (p < 0.01) increased DFT values from
      baseline (9.8 +/- 3.9 to 15.7 +/- 5.8 J and 8.9 +/- 2.9 to 14.7 +/- 5.4 J,
      respectively) and increased QRS duration from baseline during right ventricular
      pacing (89 +/- 6 to 109 +/- 10 ms; p < 0.01; and 87 +/- 6 to 103 +/- 12 ms; p <
      0.01). Lidocaine alone reduced right ventricular action potential duration (APD)
      in groups 1 and 2 (214 +/- 18 to 206 +/- 20 ms; p < 0.10; and 228 +/- 8 to 212 +/
      8 ms; p < 0.05), respectively, and it reduced paced JT interval in both groups
      (194 +/- 20 to 184 +/- 18 ms; p < 0.10; and 200 +/- 12 to 183 +/- 16 ms; p <
      0.05), respectively. When hypertonic saline was added to lidocaine, DFT and QRS
      duration values were unaffected (14.7 +/- 5.4 to 16.1 +/- 3.7 J and 103 +/- 12 to
      100 +/- 11 ms, respectively). However, APD and JT intervals returned to basal
      values when hypertonic saline was added to lidocaine (212 +/- 8 to 225 +/- 13; p
      < 0.05; and 183 +/- 16 to 192 +/- 18; p < 0.05, respectively). When D5W was added
      in the control group, no changes occurred in DFT or electrophysiologic values.
      Lidocaine slowed ventricular conduction velocity and reduced APD. The
      administration of hypertonic saline to increase extracellular sodium
      concentrations failed to reverse the effect of lidocaine on conduction-velocity
      slowing or elevated DFT values. Hypertonic saline did reverse the effects of
      lidocaine on repolarization parameters. These data suggest that shortening of
      repolarization is not a mechanism by which lidocaine makes it more difficult to
      defibrillate the heart.

PMID- 9007673
TI  - In swine myocardium, the infarct size reduction induced by U-89232 is
      glibenclamide sensitive: evidence that U-89232 is a cardioselective opener of ATP
      sensitive potassium channels.
AB  - We determined whether U-89232, a derivative of the ATP-sensitive potassium (KATP)
      channel opener cromakalim, is cardioselective and whether its action on the
      myocardium is still sensitive to glibenclamide. Experiments were performed in
      open-chest pigs subjected to a 60-min occlusion of the left anterior descending
      coronary artery (LADCA) and to 2 h of reperfusion. Four groups of animals were
      studied (n = 6 each). Animals received either U-89232, 3 mg/kg i.v. over a 15-min
      period (U), or glibenclamide, a selective KATP channel blocker, 1 mg/kg i.v. over
      a 15-min period (GLI) before the LADCA occlusion. In the GLI + U group, first
      glibenclamide (1 mg/kg/15 min) and then U-89232 (3 mg/kg/15 min) were infused
      before the 60 min of ischemia. Saline-treated animals served as controls (CON).
      Hemodynamic parameters were continuously monitored. Regional contractile wall
      function was quantified with ultrasonic crystals aligned to measure wall
      thickening. At the end of the protocol, infarct size (IS, as percentage of risk
      region) was determined by incubating the myocardium with p-nitrobluetetrazolium.
      With comparable myocardium at risk, infusion of U-89232 before 60 min of LADCA
      occlusion significantly reduced infarct size (IS, 18.5 +/- 3.7%; p < 0.001 vs.
      63.2 +/- 3.3% for the controls), whereas glibenclamide had no effect on infarct
      size (IS, 69.5 +/- 4.4%). The administration of glibenclamide before U-89232
      infusion blocked the infarct size-reducing effect of U-89232 [IS, 61.2 +/- 9.1
      (NS) vs. controls and p < 0.001 vs. U]. Infusion of U-89232 had no effect on
      hemodynamic parameters or on regional wall function. At least in a pig model, U
      89232 appears to be a cardioselective KATP channel opener, because in the absence
      of hemodynamic alterations, it exhibits a profound cardioprotective effect, which
      is fully reversible by blocking KATP channels.

PMID- 9007675
TI  - Interleukin-2 increases transcapillary diffusion of sodium fluorescein in human
      skin.
AB  - Immunotherapy with interleukin-2 (IL-2) has been limited by dose-dependent
      systemic toxicities secondary effects inducing a "vascular leak" syndrome. The
      purpose of our study was directly to observe and to quantitate changes in skin
      capillary permeability in response to microinjection of IL-2 by measuring
      transcapillary diffusion of sodium fluorescein. Twelve healthy volunteers were
      studied. IL-2 (2.5 microliters; 45,000 i.u.) was injected into the subepidermal
      skin layer of the distal tibial plateau by using a new microinjection technique.
      At the opposite leg, an equivalent amount of the solvent was injected to serve as
      the intraindividual control site. Three and 24 h after injection, Na-fluorescein
      was given intravenously, and transcapillary diffusion of the dye was
      simultaneously recorded with two different video microscopes. Perivascular
      fluorescent light intensities (FLI) corresponding to transcapillary diffusion of
      the dye were measured in arbitrary units (AU) by videodensitometry around the
      sites of microinjection during playback of the videotapes. Mean FLI values
      representing microvascular permeability 10 s after dye appearance were at 3 h,
      1,504 +/- 592 AU for IL-2 and 983 +/- 652 AU for the solvent; and at 24 h, 2,450
      +/- 447 AU for IL-2 and 658 +/- 329 AU for the solvent. At 3 and 24 h, the mean
      values after IL-2 application were significantly enhanced (p < 0.05-0.005) when
      compared with the mean values after injection of the solvent. The results
      document that IL-2, as compared with the solvent, significantly increases
      transcapillary diffusion of Na-fluorescein, reflecting capillary permeability in
      human skin. The increase in capillary permeability may explain the edema
      promoting effect of IL-2 after systemic application.

PMID- 9007674
TI  - Thyroid hormone stimulates Na(+)-Ca2+ exchanger expression in rat cardiac
      myocytes.
AB  - We investigated whether thyroid hormone directly affects Na(+)-Ca2+ exchanger
      expression in cardiac myocytes. Cultured neonatal rat cardiocytes were prepared
      from 1-day-old Sprague-Dawley rats. Intracellular Na+ concentration ([Na+]i) in
      cardiocytes was measured by using the Na(+)-sensitive dye sodium-binding
      benzofran isophthalate (SBFI). Na(+)-Ca2+ exchanger messenger RNA (mRNA) and
      protein expression were assayed by Northern and Western blotting, respectively.
      Triiodothyronine (T3; 10(-8) M) showed no effect on [Na+]i in cardiocytes,
      whereas ouabain (100 microM) caused a significant increase in [Na+]i from 11.3 +/
      5.0 to 21.8 +/- 5.0 mM. Exposure of cardiocytes to ouabain caused a rapid
      increase in Na(+)-Ca2+ exchanger mRNA accumulation, with a maximal twofold
      elevation at 12 h. The ouabain-induced Na(+)-Ca2+ exchanger mRNA accumulation was
      still observed in the Ca(2+)-free culture medium. On the other hand, exposure of
      cardiocytes to T3 induced a gradual increase in Na+ exchanger mRNA accumulation,
      with a maximal threefold increase at 24 h. Even in Na(+)-free medium, T3 still
      induced a twofold increase in Na(+)-Ca2+ exchanger mRNA accumulation in
      cardiocytes. Exposure of cardiocytes to T3 for 24-48 h also caused a marked
      increase in Na(+)-Ca2+ exchanger protein accumulation. In conclusion, thyroid
      hormone directly increases cardiac Na(+)-Ca2+ exchanger expression, independent
      of alterations in Na+ mobilization. These findings suggest also that thyroid
      hormone and Na+ regulate Na(+)-Ca2+ exchanger gene expression through distinct
      molecular regulatory pathways.

PMID- 9007676
TI  - Endothelin-receptor antagonist FR 139317 reduces infarct size in a rabbit model
      when given before, but not after, coronary artery occlusion.
AB  - Endothelins are potent vasoactive peptides that exist as isoforms having
      different affinities for two main receptor subtypes, ETA and ETB. Based on their
      potential to produce adverse effects as a result of marked vasoconstrictor
      actions, these mediators have been widely studied to investigate their role in
      disease states involving the cardiovascular system. In this study, we examined
      the effect of a selective ETA-receptor antagonist, FR 139317, on myocardial
      infarct size by using a rabbit arterial-occlusion model. The main coronary artery
      of 32 New Zealand white rabbits was occluded for 60 min, followed by 3 h of
      reperfusion. Sixteen animals received FR 139317 (5.0 mg/kg as a bolus + 30 mg/kg
      given over a 90-min period), whereas the remaining 16 control rabbits received
      the drug vehicle. Treatment began at 15 min before coronary artery occlusion and
      ended at 15 min after the start of tissue reperfusion. Infarct size, expressed as
      a percentage of the area at risk of infarction, was 64 +/- 4% in the control
      group and 41 +/- 2% in the treated animals (p < 0.001). In a second set of
      rabbits, five animals received the same treatment regimen and were compared with
      five controls; however, unlike the initial protocol, treatment was initiated 45
      min after coronary artery occlusion (15 min before reperfusion) and ended after
      75 min of reperfusion. In this case, infarct size was 65 +/- 4% in the control
      group and 56 +/- 10% in the animals that received FR 139317 (NS). The results
      suggest that endothelin is involved in the extension of myocardial infarction in
      this rabbit model and that its primary action is manifest during occlusion of the
      coronary artery.

PMID- 9007677
TI  - Noradrenaline content and release in male and female rat tail arteries.
AB  - In tail-artery segments isolated from male and female control and gonadectomized
      rats, noradrenaline content and noradrenaline released by electrical stimulation
      were measured by high-pressure liquid chromatography. Noradrenaline content,
      expressed as a function of tissue wet weight, was higher in tail arteries from
      female than from male rats, but there were no significant differences between
      control and orchiectomized males or control and ovariectomized females.
      Electrical stimulation of vascular segments in the presence of cocaine (10(-5) M)
      and deoxycorticosterone (10(-5) M) induced release of noradrenaline that was
      increased in the presence of the alpha 2-adrenergic antagonist idaxozan (10(-6)
      M). However, no differences were found in either basal or stimulation-evoked
      fractional noradrenaline release between male or female, control or
      gonadectomized animals. These results indicate that control of noradrenaline
      release at the nerve ending does not appear to be different between genders.
      There may be differences in adrenergic density, but noradrenaline content does
      not appear to be modified by circulating gonadal hormones.

PMID- 9007678
TI  - Mechanism of resistance to alpha-adrenergic receptor antagonists of renal nerve
      stimulation-induced vasoconstriction at low frequencies.
AB  - To determine why renal vasoconstriction elicited by periarterial nerve
      stimulation (RNS) at lower frequencies (< 4 Hz) is resistant to alpha-adrenergic
      receptor blockade in the rat kidney, we reevaluated the effect of alpha-receptor
      antagonists on the vasoconstrictor response to norepinephrine (NE) and to RNS and
      on the release of adrenergic transmitter. The alpha-receptor antagonist prazosin
      (PZ) at 0.2 and 7 nM reduced the vasoconstrictor response to NE, and 2.4 microM
      PZ abolished it. PZ (0.2 or 7 nM) reduced RNS-induced vasoconstriction without
      altering the fractional tritium overflow. PZ (2.4 microM) enhanced fractional
      tritium overflow and reduced the vasoconstrictor response to RNS at 2-10 Hz, but
      not at 0.5 or 1 Hz. The effect of 0.2 nM PZ to reduce RNS-induced
      vasoconstriction was reversed by increasing the concentration to 2.4 microM.
      Corynanthine (COR; 2.6 microM), a preferential alpha-receptor blocker, or
      phenoxybenzamine (PBZ; 30 nM) abolished the vasoconstrictor response to NE but
      only partially reduced response to RNS and enhanced the fractional tritium
      overflow. Rauwolscine (RW; 2.5 nM), a preferential alpha 2-receptor antagonist,
      did not alter the vasoconstrictor response to NE but potentiated RNS-induced
      vasoconstriction and fractional tritium overflow. RW (7.7 microM) inhibited NE
      induced vasoconstriction but potentiated the vasoconstrictor response to RNS and
      fractional tritium overflow. PZ (7 nM) abolished the potentiation by RW and
      reduced the vasoconstrictor response to RNS. These data suggest that a component
      of RNS-induced vasoconstriction in the rat kidney is attributable to co-release
      of a nonadrenergic transmitter with NE. The diminished effect of alpha-receptor
      antagonists at higher concentrations (e.g., PZ 2.4 microM) to reduce RNS-induced
      vasoconstriction is caused by their prejunctional action to enhance co-release of
      the nonadrenergic transmitter.

PMID- 9007679
TI  - Comparison of proarrhythmogenic effects of two potassium channel openers,
      levcromakalim (BRL 38227) and nicorandil (RP 46417): a high-resolution mapping
      study on rabbit heart.
AB  - This study was designed (a) to test and (b) to compare proarrhythmic effects of
      levcromakalim and nicorandil; and (c) determine the mechanism of arrhythmia
      initiation by using high-resolution ventricular epicardial mapping on 44
      Langendorff-perfused rabbit hearts. Eighteen hearts were kept intact and received
      incremental doses (1-500 microM) of levcromakalim, nicorandil, and isosorbide
      dinitrate. In 26 hearts, a thin layer of epicardium was obtained after
      endocardial cryotechnique (frozen hearts). In intact hearts, isosorbide dinitrate
      did not produce any arrhythmia. In contrast, levcromakalim induced spontaneous
      ventricular fibrillation (VF) in all hearts at 50 microM, whereas only one VF
      occurred at 500 microM nicorandil. These three drugs produced a dose-dependent
      bradycardia in intact hearts. In frozen hearts, arrhythmias were induced by 5
      microM levcromakalim and 50 microM nicorandil. Isosorbide dinitrate had no
      proarrhythmogenic effect. Epicardial mapping showed that most of induced
      ventricular tachycardias were based on reentry around an arc of functional
      conduction block. Ventricular conduction velocities did not change, but
      levcromakalim and nicorandil shortened ventricular effective refractory period.
      We conclude that (a) levcromakalim and nicorandil, used in toxic concentrations,
      have direct proarrhythmic effects; (b) nicorandil proarrhythmogenic effects are
      10 times less marked than those of levcromakalim (arrhythmia is solely the result
      of the potassium channel opener property of nicorandil); and (c) most of
      ventricular tachycardias induced are based on reentry.

PMID- 9007680
TI  - The practical assessment of compliance with ACE-inhibitor therapy--a novel
      approach.
AB  - Poor compliance may be responsible for symptomatic decompensation or
      neurohormonal "escape" in patients with heart failure treated over the long term
      with angiotensin-converting enzyme-1 (ACEI) drugs. Serum ACE activity is a poor
      index of neurohormonal suppression or haemodynamic effect after ACE-inhibitor
      treatment. Serum ACE activity may, however, be a useful index of compliance with
      treatment, as serum ACE is sensitive to the presence of an ACE inhibitor in the
      blood. Sixteen normotensive male volunteers of known ACE genotype received 7 days
      of randomised, double-blind therapy on four occasions 2 weeks apart with
      lisinopril 20 mg (L) or matched placebo (P) to simulate (A) noncompliance (all
      P), (B) full compliance (all L), (C) partial compliance (L days, 1, 3, 6; P days,
      2, 4, 5, 7), or (D) single dose (L day 7; P, 1-6). Supine (30 min) blood pressure
      (BP)/heart rate (HR), ACE, and angiotensins were measured on d7 before dose and 4
      6 h after dose. Results are mean +/- 1 SD. BP showed the expected small decrease
      with active treatment on d7 (B or D) but not with placebo (A) or partial
      compliance (C). Prestudy serum ACE, despite a wide range (16-124 U/L), was
      reproducible within subjects [coefficient of variation (CV), 1.7%]. Serum ACE
      activity, before (41.9 +/- 30) and after (41 +/- 30) angiotensin (A) I or II,
      were unaffected by treatment (placebo A). Active treatment (B) resulted in very
      low serum ACE activity and d7 and a small further suppression after dosing
      (before, 3.9 +/- 4; after, 1.8 +/- 4). AI was elevated in this group with further
      elevation after dosing (before, 234 +/- 116; after, 551 +/- 250). AII was only
      modestly reduced from baseline and showed little further suppression after dosing
      (before, 7.8 +/- 4; after, 6.3 +/- 5). Partial compliance (C) showed low ACE but
      no reduction after treatment (before, 7 +/- 3; after, 7 +/- 4), an elevated AI
      but no dosing effect (before, 187 +/- 198; after, 200 +/- 151) and reduced AII
      but with no further dose suppression (before, 6.4 +/- 3.4; after, 7 +/- 4)
      induced increase in peptide (compared with B). Single-dose treatment (D) showed
      ACE inhibition as expected (before, 47 +/- 30; after, 2.2 +/- 3). There was a
      dosing-related increase of AI but to a lesser extent than seen with chronic
      active dosing (B) (before, 39 +/- 10; after, 240 +/- 200). In contrast to long
      term dosing, there was marked ANG II suppression (before, 8.8 +/- 4; after, 2.9
      +/- 3). With this long-acting ACEI in a dose relevant to congestive heart failure
      management, we suggest that 4-6 h after-dosing serum ACE (< 5 EU/L) and elevated
      ANG I (> 300 pg/ml) can be used to confirm compliance with treatment. These
      absolute values may be altered in patients treated concomitant with loop
      diuretics. In principle, however, this may be a useful tool in clinical trials or
      in clinical practice after further work has been done to assess the limits in
      patients across the doses and across the range of available drugs used.

PMID- 9007681
TI  - Effect of captopril and losartan on blood pressure and accumulation of LDL and
      fibrinogen by aortic wall and other tissues in normotensive and hypertensive
      rats.
AB  - Hypertension, low-density lipoprotein (LDL), and fibrinogen are risk factors for
      atherosclerosis. We investigated the effect of reducing blood pressure, by
      blocking the renin-angiotensin system (RAS), on the accumulation of these
      atherogenic proteins in arterial walls and other tissues in conscious,
      unrestrained, normotensive and hypertensive rats. The accumulation of LDL and
      fibrinogen, labeled respectively with 125I and 131I via the adduct tyramine
      cellobiose ([125I]-TC-LDL and [131I]-TC-fibrinogen) was compared in aortic walls,
      heart, lung, skeletal muscle, liver, kidney, and adrenal gland during the final
      24 h of treatment with either the angiotensin-converting enzyme (ACE) inhibitor
      captopril or the angiotensin II-receptor I (AT1) antagonist losartan. In
      normotensive rats, the blood pressure was decreased only by losartan. In
      spontaneously hypertensive rats (SHRs), the blood pressure was decreased by both
      losartan and captopril. Captopril had no significant effect on the accumulation
      of LDL or fibrinogen by the aortic wall. Losartan significantly increased the
      accumulation of LDL by the aortic wall of SHRs. Neither agent produced any change
      in LDL or fibrinogen accumulation in any of the other tissues. These results
      indicate that although blocking the RAS at either the enzymic or receptor level
      produces significant decrease of blood pressure in hypertensive animals, only
      losartan has any affect on LDL accumulation by the aortic wall.

PMID- 9007682
TI  - ATP-sensitive potassium channels in isolated rat aorta during physiologic,
      hypoxic, and low-glucose conditions.
AB  - In arterial smooth muscle, adenosine triphosphate (ATP)-sensitive potassium
      channels are the targets of a variety of synthetic and endogenous vasodilators.
      In this study, we evaluated the influence of glibenclamide, an ATP-sensitive K(+)
      channel blocker, on various vasodilator responses, including those by
      levcromakalim under hypoxic and low-glucose conditions in isolated rat aortic
      rings. The concentration-response curves induced by methacholine and sodium
      nitroprusside (after precontraction with 1 microM phenylephrine) were not
      affected by glibenclamide. Glibenclamide influenced neither the adenosine- nor
      the iloprost- (a stable prostacyclin) induced vasodilator effects. Glibenclamide
      caused a concentration-dependent rightward shift of the concentration-response
      curves of levcromakalim. The vascular tone induced by phenylephrine was not
      affected under low-glucose conditions, whereas hypoxia caused a decrease in the
      phenylephrine-induced contraction when compared with that under normal
      circumstances. Under all conditions, glibenclamide did not influence the
      phenylephrine-induced increase in vascular tone. Under low-glucose and hypoxic
      conditions, the concentration-response curves for levcromakalim showed a
      significantly less steep slope than under normal conditions, and higher
      concentrations of glibenclamide were necessary to inhibit the vasodilator
      response induced by levcromakalim under these experimental conditions adopted to
      mimic pathologic conditions. In conclusion, methacholine, sodium nitroprusside,
      adenosine, and iloprost appear not to induce vasodilation in the rat aorta by
      glibenclamide-sensitive K+ channels, whereas hypoxia and low-glucose levels cause
      an impaired function of the glibenclamide-sensitive K+ channels.

PMID- 9007683
TI  - Endothelin-1 inhibits L-type Ca2+ current enhanced by isoprenaline in rat atrial
      myocytes.
AB  - Endothelin-1 (ET-1) was shown to exert direct cardiac effects by complex
      signaling pathways and to interact with neurotransmitter regulation of cardiac
      activity. The effect of ET-1 was investigated on the beta-adrenergic stimulation
      of cardiac L-type Ca2+ current (ICaL) on isolated rat atrial myocytes by using
      the patch-clamp technique. ET-1 (5 x 10(-8) M) reversed the increase in ICaL
      induced by isoprenaline (10(-6) M) but had no effect on basal ICaL and on (-) Bay
      K 8644-increased ICaL (10(-6) M); so ET-1 might exert an effect only when the
      Ca2+ channels are phosphorylated. The antiadrenergic action of ET-1, blocked by
      BQ-123 (10(-6) M) and unaffected by IRL 1038 (3.5 x 10(-8) M) should be mediated
      by ET-A receptors. The inhibitory action of ET-1 was still observed when ICaL was
      previously increased by forskolin (3 x 10(-6) M), 8-bromo-cyclic adenosine
      monophosphate (8-Br-cAMP; 200 microM), or cAMP (100 microM) in presence of
      isobutyl methyl xanthine (IBMX; 10(-6) M), suggesting that the antiadrenergic
      action of ET-1 on ICaL was exerted independent of the cAMP-dependent
      phosphorylation pathway. ET-1 is known to be an activator of phosphoinositide
      hydrolysis, resulting in an increased production of IP3 and diacylglycerol (DAG).
      A Ca(2+)-dependent inhibition of ICaL consequently to an elevation of the
      intracellular Ca2+ pool via IP3 might be excluded in the action of ET-1, because
      of the presence of EGTA in the intrapipette medium. ET-1 reversed the
      isoprenaline-induced increase in ICaL in the presence of protein kinase C
      inhibitor [PKC(19-31); 100 microM), making unlikely the involvement of a DAG
      dependent activation of PKC. Therefore the antiadrenergic action of ET-1 might
      also be independent on the phosphoinositide pathway.

PMID- 9007685
TI  - E-state fields: applications to 3D QSAR.
AB  - The derivation of a new 3D QSAR field based on the electrotopological state (E
      state) formalism is described. A complementary index and its associated field,
      the HE-state, describing the polarity of hydrogens is also defined. These new
      fields are constructed from a nonempirical index that incorporates
      electronegativity, the inductive influence of neighboring atoms, and the
      topological state into a single atomistic descriptor. The classic CoMFA steroid
      test data set was examined with models incorporating the E-state and HE-state
      fields alone and in combination with steric, electrostatic and hydropathic
      fields. The single best model was the E-state/HE-state combination with q2 =
      0.803 (three components) and r2 = 0.979. Using the E-state and/or HE-state fields
      with other fields consistently produced models with improved statistics, where
      the E-state fields provided a significant, if not dominant, contribution.

PMID- 9007684
TI  - The measurement of molecular diversity: a three-dimensional approach.
AB  - This paper describes a method for selecting a small, highly diverse subset from a
      large pool of molecules. The method has been employed in the design of
      combinatorial synthetic libraries for use in high-throughput screening for
      pharmaceutical lead generation. It computes diversity in terms of the main
      factors relevant to ligand-protein binding, namely the three-dimensional
      arrangement of steric bulk and of polar functionalities and molecular entropy.
      The method was used to select a set of 20 carboxylates suitable for use as side
      chain precursors in a polyamine-based library. The method depends on estimates of
      various physical-chemical parameters involved in ligand-protein binding;
      experiments examined the sensitivity of the method to these parameters. This
      paper compares the diversity of randomly and rationally selected side-chain sets;
      the results suggest that careful design of synthetic combinatorial libraries may
      increase their effectiveness several-fold.

PMID- 9007686
TI  - The comparison of geometric and electronic properties of molecular surfaces by
      neural networks: application to the analysis of corticosteroid-binding globulin
      activity of steroids.
AB  - It is shown how a self-organizing neural network such as the one introduced by
      Kohonen can be used to analyze features of molecular surfaces, such as shape and
      the molecular electrostatic potential. On the one hand, two-dimensional maps of
      molecular surface properties can be generated and used for the comparison of a
      set of molecules. On the other hand, the surface geometry of one molecule can be
      stored in a network and this network can be used as a template for the analysis
      of the shape of various other molecules. The application of these techniques to a
      series of steroids exhibiting a range of binding activities to the corticosteroid
      binding globulin receptor allows one to pinpoint the essential features necessary
      for biological activity.

PMID- 9007687
TI  - Tautomerism of xanthine and alloxanthine: a model for substrate recognition by
      xanthine oxidase.
AB  - Tautomerism of neutral xanthine and alloxanthine has been examined both in the
      gas phase and in aqueous solution. The tautomeric preference in the gas phase has
      been studied by means of semiempirical and ab initio quantum-mechanical
      computations with inclusion of correlation effects at the Moller-Plesset level,
      and from density-functional calculations. The influence of solvent on the
      relative stability between tautomers has been estimated from self-consistent
      reaction field calculations performed with different models. The results provide
      a detailed picture of tautomerism for these biologically relevant purine bases.
      The functional implications in the recognition by xanthine oxidase are analyzed
      from inspection of the interaction patterns of the most stable tautomeric forms.
      A model for the recognition of these purine derivatives in the enzyme binding
      site is discussed.

PMID- 9007688
TI  - Pharmacophore development for antagonists at alpha 1 adrenergic receptor
      subtypes.
AB  - Many receptors, including alpha 1 adrenergic receptors, have a range of subtypes.
      This offers possibilities for the development of highly selective antagonists
      with potentially fewer detrimental effects. Antagonists developed for alpha 1A
      receptors, for example, would have potential in the treatment of benign prostatic
      hyperplasia. As part of the molecular design process, structural features
      necessary for the selective affinity for alpha 1A and alpha 1B adrenergic
      receptors have been investigated. The molecular modelling software (particularly
      the Apex module) of Molecular Simulations, Inc. was used to develop pharmacophore
      models for these two subtypes. Low-energy conformations of a set of known
      antagonists were used as input, together with a classification of the receptor
      affinity data. The biophores proposed by the program were evaluated and
      pharmacophores were proposed. The pharmacophore models were validated by testing
      the fit of known antagonists, not included in the training set. The critical
      structural feature for selectivity between the alpha 1A and alpha 1B adrenergic
      receptor sites is the distance between the basic nitrogen atom and the centre of
      an aromatic ring system. This will be exploited in the design and synthesis of
      structurally new selective antagonists for these sites.

PMID- 9007689
TI  - Reconstruction of the 3D coordinates of alpha-carbon atoms of proteins from a
      pair of stereographic figures.
AB  - In an attempt to promptly use the experimentally determined structures of
      proteins in modeling studies, we have developed the program ReconstC alpha to
      generate the 3D coordinates of alpha-carbon atoms from a pair of stereographic
      figures. Calculations of the 3D coordinates were performed by estimating the
      stereo parameters systematically. Geometrical features of C alpha traces were
      used to evaluate the integrity of the calculated structure. The program was
      applied to four kinds of protein structures to examine the performance. It was
      found that the root-mean-square deviation of atomic positions between constructed
      and reference crystal structures ranged from 0.36 to 0.78 A. The range represents
      a reasonable accuracy and its automatic feature suggests that our approach would
      be expedient for providing initial structures for protein modeling studies.

PMID- 9007691
TI  - Mechanism of action of aspartic proteinases: application of transition-state
      analogue theory.
AB  - Applying the semiempirical MO methods AM1 and PM3 as well as the density
      functional theory to the model of the catalytic site composed of ca. 160-190
      atoms, we have carried out studies aimed at the explanation of three aspects of
      the mechanism of action of aspartic proteinases: the site of dissociation within
      the catalytic diad COOH/COO- (i) in the free enzyme and (ii) in the Michaelis
      complex, and (iii) the energy changes associated with the catalytic paths. We
      have found that the state of dissociation within the catalytic diad is ligand
      sensitive. In the free enzyme and in the intermediate complexes, Asp33 prefers to
      be dissociated with the outer oxygen of Asp213 protonated, while in the Michaelis
      and product complexes the opposite holds true. This is in agreement with recent
      mechanistic hypotheses and with some experimental results by FTIR and NMR. The
      energy diagram for the catalysis indicates that electronic effects are
      responsible most of all for the relative reduction of energy of the intermediates
      and possibly transition states on the catalytic reaction path. The shape of the
      diagram qualitatively agrees with the transition-state analogue theory for the
      enzymatic reactions.

PMID- 9007690
TI  - A 3D QSAR CoMFA study of non-peptide angiotensin II receptor antagonists.
AB  - A series of non-peptide angiotensin II receptor antagonists was investigated with
      the aim of developing a 3D QSAR model using comparative molecular field analysis
      descriptors and approaches. The main goals of the study were dictated by an
      interest in methodologies and an understanding of the binding requirements to the
      AT1 receptor. Consistency with the previously derived activity models was always
      checked to contemporarily test the validity of the various hypotheses. The
      specific conformations chosen for the study, the procedures invoked to
      superimpose all structures, the conditions employed to generate steric and
      electrostatic field values and the various PCA/PLS runs are discussed in detail.
      The effect of experimental design techniques to select objects (molecules) and
      variables (descriptors) with respect to the predictive power of the QSAR models
      derived was especially analysed.

PMID- 9007692
TI  - Modelling steric effects in DNA-binding platinum(II)-am(m)ine complexes.
AB  - A repulsive energy strategy has been employed in an attempt to delineate the
      steric contribution to the biological profile of a variety of platinum-am(m)ine
      complexes. Thus, relative steric descriptors have been calculated for the amine
      ligands themselves by the Ligand Repulsive Energy (LRE) methodology. This has
      been extended to a Complex Repulsive Energy (CRE) strategy whereby the steric
      requirements of the approach of a metal complex to a site on a target molecule
      may be evaluated. Specifically, the monodentate approach of a variety of platinum
      am(m)ine complexes to the N7 site of a guanine moiety has been considered. The
      steric descriptors thus obtained have been used in QSAR analysis, resulting in
      improved regression equations. Attempts have also been made to relate the above
      descriptors to various biological indicators for given series of complexes. These
      investigations suggest an optimum steric requirement for minimum toxicity, which
      could aid in the rational design of such agents.

PMID- 9007693
TI  - Three-dimensional hydrogen-bond geometry and probability information from a
      crystal survey.
AB  - An extensive crystal survey of the Cambridge Structural Database has been carried
      out to provide hydrogen-bond data for use in drug-design strategies. Previous
      crystal surveys have generated 1D frequency distributions of hydrogen-bond
      distances and angles, which are not sufficient to model the hydrogen bond as a
      ligand-receptor interaction. For each hydrogen-bonding group of interest to the
      drug designer, geometric hydrogen-bond criteria have been derived. The 3D
      distribution of complementary atoms about each hydrogen-bonding group has been
      ascertained by dividing the space about each group into bins of equal volume and
      counting the number of observed hydrogen-bonding contacts in each bin. Finally,
      the propensity of each group to form a hydrogen bond has been calculated.
      Together, these data can be used to predict the potential site points with which
      a ligand could interact and therefore could be used in molecular-similarity
      studies, pharmacophore query searching of databases, or de novo design
      algorithms.

PMID- 9007694
TI  - An inequality for 3D database searching and its use in evaluating the treatment
      of conformational flexibility.
AB  - A mathematical formula is introduced for predicting the number of hits that
      should be observed in a flexible 3D database search, based on the results of a
      set of related queries. The projected number of hits is always greater than or
      equal to the actual number of hits, the discrepancy being due to imperfect
      treatment of conformational flexibility of the molecules. Hence, the difference
      between the projected and actual number of hits, delta, serves to measure how
      well conformational flexibility is being treated, in a manner that is objective,
      easy for a user to quickly verify, and independent of the particular algorithm
      for flexible 3D database search. It is shown that delta is a function both of how
      well conformational flexibility is treated and of the precision of the query.
      When the distance constraint is defined only to a precision of +/- 2.0 A, in a
      single-conformer database of drug-like molecules delta values of only 0.03 are
      found, while in a single-conformer database of di- and tripeptides, delta is
      0.15. At increased precision, a flexible 3D database search becomes critical. For
      a single-conformer database, using a query of precision +/- 0.2 A, applied to a
      database of drug-like molecules, delta is 0.97; applied to a database of di- and
      tripeptides, delta is 2.21. By contrast, treating conformational flexibility by
      storing up to 100 conformers per molecule, at this precision, applied to a
      database of drug-like molecules, delta is 0.002; applied to a database of di- and
      tripeptides, delta is 0.07. This inequality, and hence delta, is defined only for
      database queries containing a single distance constraint; how the inequality may
      generalize to higher-dimensional queries is still unclear.

PMID- 9007695
TI  - Endocrine mechanisms of suppressive effect of low dose estrogen-antiandrogen
      treatment on androgen-dependent organs of male rats.
AB  - The effects of low doses of hexestrol (Hex) (2-40 micrograms/kg bw) and flutamide
      (FI) (10 mg/kg bw) on some endocrine mechanisms in mature intact male rats are
      described in the present paper. It has been shown that each preparation,
      administered separately for 10 days, induced a moderate decrease in the weight of
      the ventral prostate (VP), anterior prostate lobe or coagulating gland (CG) and
      seminal vesicles (SV), in the DNA content and number of cells in the VP. 5 alpha
      reductase activity was also decreased; the epithelium secretory activity of the
      VP was suppressed. After combined FI (10 mg/kg bw) and Hex (40 micrograms/kg bw)
      the following castration-like effects were observed: an abrupt fall in the weight
      of the accessory sexual glands, a decrease of DNA level and cell number in the VP
      as well as a suppression of the production of 5 alpha-reductase metabolites in
      this structure. Histologically, a marked degenerative changes in the VP secretory
      epithelium was observed; on the contrary an hyperplasia of connective and smooth
      muscle cells was evident. When FI alone was administered to rat, the above
      mentioned changes were accompanied by a pronounced elevation of plasma bio-LH and
      testosterone (T) levels, also an increase of testicular delta 5-3 beta
      hydroxysteroid dehydrogenase activity was observed. On the contrary, when Hex was
      administered alone or in combination with FI, bio-LH and T levels and enzyme
      activity decreased. We conclude that Hex administration in low doses, in
      combination with FI, could be an alternative method for a complete androgen
      blockade of the accessory sexual glands.

PMID- 9007696
TI  - Transforming growth factor-alpha, like epidermal growth factor, stimulates cell
      proliferation and inhibits prolactin secretion in the human decidual cells in
      vitro.
AB  - In order to clarify the biological action of transforming growth factor alpha
      (TGF-alpha) in the human decidua, we investigated the effects of TGF-alpha on
      cell proliferation and prolactin (PRL) secretion in cultured decidual cells in
      vitro. TGF-alpha had a stimulatory effect on DNA synthesis in decidual cells and
      an inhibitory effect on PRL secretion from these cells. These results suggest
      that TGF-alpha, like epidermal growth factor (EGF), may be one of the substances
      which regulate decidual function.

PMID- 9007697
TI  - Gonadotrophin and free alpha-subunit secretion in patients with acromegaly and
      clinically non-functioning pituitary tumors: anterior pituitary function and the
      effect of thyrotrophin-releasing hormone.
AB  - The effect of the tumor size on the anterior pituitary hypofunction is analyzed
      in 29 patients with acromegaly and 34 patients with clinically non-functioning
      pituitary tumor (NFPA). Gonadotrophin and free alpha-subunit (SU) concentrations
      during daytime variations (samples were taken hourly for 24 h) and after
      stimulation with TRH were measured as well. Patients with NFPA had a higher
      prevalence of isolated secondary hypogonadism (20.6% vs 10.3%) and more severe
      pituitary failure (52.9% vs 6.9%) in comparison with acromegalic patients (p <
      0.0001). However, there was no association between the tumor size and the
      anterior pituitary hypofunction (p = 0.1 and p = 0.9) in patients with NFPA and
      acromegaly respectively. In premenopausal women and in men with normal/low
      gonadotrophin levels, mean daytime levels of LH (0.75 +/- 0.6 vs 1.5 +/- 1.9
      mlU/ml; p = 0.002) and FSH (2.1 +/- 2.7 vs 4.1 +/- 4.9 mlU/ml; p = 0.009) were
      higher in patients with acromegaly. There was no difference in the alpha-SU level
      (p = 0.9). Women with gonadotrophin levels compatible with menopause and men with
      elevated gonadotrophin levels had the same degree of gonadotrophin and alpha-SU
      elevation regardless of the tumor type. TRH induced significant rise of LH in 8
      (23.5%), FSH in 5 (14.7%) and alpha-SU in 10 (29.4%) patients with NFPA. Among 29
      patients with acromegaly LH rose in 6 (20.7%), FSH in 5 (17.2%) and alpha-SU in 3
      (10.3%) patients. In conclusion, the anterior pituitary function is better
      preserved in patients with acromegaly than in patients with NFPA. It seems that
      the size of pituitary tumor is not the major factor in the pathogenesis of
      hypopituitarism in patients with macroadenomas. Gonadotrophin and possibly alpha
      SU response to TRH exists not only in some patients with clinically non
      functioning pituitary tumors but also in some patients with acromegaly. Further
      investigations are need to explain if it represents a biochemical marker of a
      plurihormonal pituitary tumor in these patients.

PMID- 9007699
TI  - Does tuberculosis really cause hypercalcemia?
AB  - Hypercalcemia has been known to be associated with tuberculosis. In some studies
      it has been reported to occur commonly. It seems that the studies in which
      tuberculosis was complicated by hypercalcemia were retrospective and therefore
      the other causes of hypercalcemia could not be excluded. We have a great deal of
      experience concerning tuberculosis and have not seen a patient with hypercalcemia
      due to tuberculosis itself. Therefore we aimed to investigate whether
      tuberculosis really cause hypercalcemia in a prospective study. We evaluated 104
      patients with tuberculosis aged between 14-85 (mean +/- SD 38.5 +/- 15) years, 73
      males and 31 females, and 50 age-matched healthy subjects aged between 19-70
      (mean +/- SD 39 +/- 13) years, 33 males and 17 females. No significant
      differences between the patients and healthy subjects were detected in terms of
      250HD3, calcium and phosphate levels. Albumin levels were significantly higher in
      the control group than in the tuberculous group (p < 0.02). No significant
      difference was found between the calcium levels measured before the therapy (2.4
      +/- 0.1 nmol/L) and after the therapy (2.4 +/- 0.2). We think that patients with
      tuberculosis are not at risk for hypercalcemia either before or during treatment
      and the development of hypercalcemia as a result of tuberculosis is rather
      doubtful and needs to be clarified.

PMID- 9007698
TI  - Evaluation of central motor conduction in hypothyroid and hyperthyroid patients.
AB  - Deficiency or excess of thyroid hormones is associated with central nervous
      system (CNS) disturbances. Although the CNS involvement either in hypothyroidism
      or in hyperthyroidism have previously been shown on the basis of visual, auditory
      and somatosensory evoked potentials studies, less is known about the function of
      central motor pathways in both disorders. We studied the motor evoked potentials
      (MEPs) following the magnetic stimulation of the motor cortex and spinal roots in
      20 patients with hypothyroidism and in 19 patients with hyperthyroidism both
      before treatment and after they became euthyroid and compared with findings in 20
      age-, sex- and height-matched control subjects. Disease duration (expressed as
      time from diagnosis of diseases to the time of neurological testing) is less than
      one month in both disorders. Central motor conduction time (CMCT) was determined
      as the differences between MEPs latencies after cortical and spinal stimulation.
      The mean CMCTs before treatment in hypothyroid patients (8.31 +/- 1.52 msec.) and
      in hyperthyroid patients (7.92 +/- 1.06 msec.) were significantly prolonged as
      compared to those in normal controls (6.82 +/- 0.83 msec. p = 0.002 and p =
      0.004, respectively). Four of the 20 (20.0%) hypothyroid patients and 2 of 19
      (10.5%) hyperthyroid patients had abnormal CMCT (values exceeding mean +2.5 SD of
      normal control). The mean CMCT values in both groups were not significantly
      decreased after euthyroidism was achieved, although a tendency of the decrease in
      CMCT was observed. Improvement of CMCT abnormalities was observed in 1 of 4
      hypothyroid patients and in one of 2 patients with hyperthyroidism, who had CMCT
      abnormalities before treatments, after they became euthyroid. No correlation was
      found between CMCT and free T3, free T4, or TSH levels as well as the onset age,
      the severity of the diseases or the disease duration in both disorders. We
      conclude that abnormal CMCT could be documented in few patients in both
      disorders. However, these alterations could not be improved completely after
      restoration of euthyrodism. Thus, it remains to be determined if long-term
      treatment would completely improve CMCT abnormalities in both disorders. Since
      abnormal CMCT values in both disorders were observed only in few patients, our
      results also suggest that CMCT measurement does not have, at present time, a
      clinical usefulness to assess the peripheral action of thyroid hormones. Thus,
      the data obtained need a more extensive evaluation.

PMID- 9007700
TI  - Relationship between thyroid-stimulating antibodies and thyrotropin-binding
      inhibitory immunoglobulins years after administration of radioiodine for Graves'
      disease: retrospective clinical survey.
AB  - Thyroid-stimulating antibody (TSAb) activity and the TSH-binding inhibitory
      immunoglobulin (TBII) index were assessed in 158 patients with Graves' disease
      who had been treated with 131I 6-14 years earlier. Twenty-one patients (13%) were
      still hyperthyroid, 45 (28%) were euthyroid, 44 (28%) were subclinically
      hypothyroid, and 48 (30%) were overtly hypothyroid. Positive results were
      obtained in 10 (48%) of the 21 patients with hyperthyroidism for both TSAb and
      TBII assays, and in 3 patients (14%) in one of the assays. In contrast, only two
      (5%) patients with subclinical hypothyroidism and 1 (2%) patient with overt
      hypothyroidism tested positive in both assays, and 11 (25%) subclinically
      hypothyroid patients and 15 (31%) overtly hypothyroid patients tested positive in
      one of the assays. The correlation coefficients between TSAb and TBII were 0.88
      (p < 0.01) in hyperthyroid patients, 0.49 (p < 0.01) in euthyroid patients, 0.34
      (p < 0.05) in subclinically hypothyroid patients, and 0.12 (p > 0.05) in patients
      with overt hypothyroidism. Findings indicate the presence of long-term changes in
      the population of TSH receptor antibodies years after 131I treatment, which may
      influence thyroid function.

PMID- 9007701
TI  - Impairment of growth hormone responsiveness to growth hormone releasing hormone
      and pyridostigmine in patients affected by Prader-Labhardt-Willi syndrome.
AB  - In order to evaluate the impairment of GH response in patients affected by Prader
      Labhardt-Willi (PLW) syndrome, in 18 patients we studied GH response to clonidine
      and to GHRH + pyridostigmine, a cholinergic drug which enhances GHRH induced GH
      responsiveness in obese patients. After clonidine GH response was abnormal in
      14/18 subjects (mean GH peak: 4.1 +/- 1.3 micrograms/l; area under curve: 208.1
      +/- 74.2 micrograms/l.h) while all but 5 patients showed an inadequate GH
      response to GHRH + pyridostigmine (mean GH peak: 13.4 +/- 2.5 micrograms/l; area
      under curve: 903.4 +/- 171.0 micrograms/l.h). However, in the three patients with
      low adiposity index, GH response to GHRH + pyridostigmine was significantly
      higher than that observed in fatter subjects. In addition, GH response to GHRH +
      pyridostigmine was negatively correlated to age and adiposity index. In
      conclusion, our data are consistent with the hypothesis of the existence of a
      complex derangement of GH neuroendocrine regulation in these subjects.

PMID- 9007702
TI  - Expression of interleukin-1 in human pheochromocytoma.
AB  - Cytokines and in particular interleukin 1 (IL-1) play a role in the micro
      environment of various tumors. In addition, it is well established that IL-1 is a
      neurotrophic, angiogenetic and fibrogenetic factor. Using in situ hybridization
      we analyzed the expression of endogenous IL-1 in human pheochromocytoma (PCC).
      With the help of specific antibodies to B- and T-cells, macrophages, and
      neuroendocrine cell antigens, we characterized the distribution and localization
      of various cell types in human PCC. The combination of immunohistochemistry and
      in situ hybridization was eminently suited to defining the exact cellular source
      of IL-1 expression. In situ hybridization and immunostaining revealed that IL-1
      mRNA was located primarily in the tumor cell itself. IL-1 may therefore
      constitute an important paracrine/autocrine factor in neuroendocrine tumors.

PMID- 9007703
TI  - Long-term octreotide treatment reduced hyperinsulinemia, excess body weight and
      skin lesions in severe obesity with acanthosis nigricans.
AB  - A boy affected by severe obesity (kg 117, Body Mass Index 37 kg/m2) and
      acanthosis nigricans, was treated with octreotide for 150 days (50 micrograms x
      three daily subcutaneous administrations). Before treatment the patient showed an
      exaggerated insulin (IRI) and C-peptide (CPR) response to a standard meal with a
      lowering in after-meal CPR/IRI molar ratio. During octreotide treatment both IRI
      and CPR response was reduced but CPR/IRI molar ratio rised after meal indicating
      an increase in hepatic insulin removal. Body weight and acanthosis nigricans were
      sharply reduced during treatment and the reduction was still maintained six
      months after the cessation of therapy. Furthermore, IRI and CPR response, as well
      as the behaviour of CPR/IRI molar ratio, remained within normal range. In
      conclusion long-term octreotide treatment has been able to correct
      hyperinsulinemia and to reduce body weight and acanthosis nigricans.

PMID- 9007704
TI  - Sequential changes in full-length genomes of hepatitis B virus accompanying acute
      exacerbation of chronic hepatitis B.
AB  - BACKGROUND/AIM: During the course of persistent hepatitis B virus infection,
      viral replication markedly decreases after acute exacerbation of liver
      inflammation accompanied by emergence of antihepatitis B e antibody (anti-HBe)
      and/or anti-hepatitis B surface antibody (anti-HBs). In some cases, however,
      persistent viral replication continues even after such exacerbation with or
      without HBeAg/anti-HBe seroconversion. The aim of the present study was to
      investigate the extent of genetic variations of HBV in this phenomenon. METHODS:
      Full-length HBV genomes were amplified by polymerase chain reaction from sera of
      three patients before and after acute exacerbation and were directly sequenced.
      RESULTS: In the whole genomes of 3215 nucleotides, only six nucleotide mutations
      for six amino acid substitutions (2 in the surface gene, 2 in the X gene, 1 in
      the core gene and 1 in the polymerase gene) were observed in patient 1, 15
      mutations for 14 amino acid substitutions (1 in the pre-core codon 28, 4 in the
      surface gene, 4 in the core gene and 5 in the polymerase gene) were observed in
      patient 2, and 5 mutations for 6 amino acid substitutions (2 in the surface gene,
      2 in the X gene, pre-core stop codon mutation and 1 in the polymerase gene) were
      observed in patient 3. Substitution in the a determinant of the surface gene,
      which encodes target epitopes for neutralizing antibodies, as well as those in
      the pre-core/core gene, which encodes epitopes for cytotoxic T cells, were mainly
      found. CONCLUSION: HBV that remained after the emergence of anti-HBe and anti-HBs
      are considered to possess mutations in epitopes for both humoral and cellular
      immunity. These mutant HBV may be involved in the pathogenesis of persistent
      hepatic injury after acute exacerbation.

PMID- 9007705
TI  - Relation between treatment efficacy and cumulative dose of alpha interferon in
      chronic hepatitis B. European Concerted Action on Viral Hepatitis (Eurohep).
AB  - BACKGROUND/AIMS: Alpha interferon (IFN) is an established treatment of chronic
      hepatitis B. The effect has been shown to be dose related, recommended dose
      regimens being associated with a doubling of the spontaneous, baseline HBeAg to
      anti-HBe seroconversion rate. However, the efficacy of IFN treatment in relation
      to the dose of IFN actually received remains to be established. The aim of this
      study was to estimate the relative efficacy of IFN as a function of the
      cumulative IFN dose. In addition we determined if and when a patient returns to
      his baseline chance of seroconversion after stopping IFN therapy. MATERIALS AND
      METHODS: Individual patient data from 10 clinical controlled trials were
      available for the present analysis, in all, 746 patients, of whom 491 received
      IFN and 255 were untreated controls. The data were analyzed performing a time
      dependent Cox regression analysis of the relative efficacy of IFN using the
      cumulative IFN dose administered up to any given time during the observation
      period and the time after termination of therapy as explanatory variables.
      RESULTS: In the proposed model, the chance of HBeAg disappearance for a treated
      patient relative to no therapy was estimated to 2.1 at a cumulative dose of 100
      MU and leveled out at about 2.8 at a cumulative dose of 500 MU. The effect of IFN
      was shown to decay rapidly after discontinuation and after 3 months a patient
      could be considered to be back to his baseline chance of HBeAg disappearance.
      These findings show that IFN administered at a dose of 15-30 MU/week should be
      considered effective (relative efficacy approximately 2) already after 1-2 months
      of treatment. CONCLUSIONS: The present findings do not lend any support to the
      concept that IFN treatment becomes less effective when a certain total dose of
      IFN has been administered or that the treatment effect reaches beyond 3 months
      after stopping IFN.

PMID- 9007707
TI  - Thymosin-alpha 1, but not interferon-alpha, specifically inhibits anchorage
      independent growth of hepatitis B viral transfected HepG2 cells.
AB  - BACKGROUND: Thymosin-alpha 1 is a biological response modifier that has been used
      clinically, alone and in combination with interferon-alpha for the treatment of
      chronic hepatitis B viral infection. Both immunomodulatory and immediate
      intracellular mechanisms have been postulated to explain the effect of these two
      agents on HBV-infected hepatocytes. METHODS: In this study, hepatitis B
      transfected HepG2 hepatoblastoma cells (HepG2-Nu2), derived from 2.2.15 cells,
      were used as an in vitro model to determine the efficacy of thymosin-alpha 1 and
      interferon-alpha, individually and combined, as proliferation inhibitors of HBV
      infected cells. For comparison, parental HepG2 cells and an SV40-transfected
      HepG2 cell line (HepG2P9T2) were also evaluated. RESULTS: In a clonogenic soft
      agar assay, thymosin-alpha 1 inhibited the anchorage-independent growth of the
      HepG2-Nu2 cells by 40% compared with untreated controls, but did not inhibit
      parental HepG2 or HepG2P9T2 clonal growth. The response was dose dependent over
      concentrations spanning three log units. In comparison, 10000 units/ml of
      interferon-alpha inhibited parental HepG2, HepG2-N4Z and HepG2P9T2 by 33%, 41%
      and 87%, respectively. The combination of thymosin-alpha 1 and interferon-alpha
      consistently inhibited HepG2-Nu2 clonal growth more effectively than either
      treatment alone, reaching maximum inhibition levels of 51%. CONCLUSIONS: Thymosin
      alpha 1 specifically inhibits the tumorigenic growth of HBV-transfected HepG2
      cells in contrast to the general inhibition displayed by interferon-alpha. This
      panel of cell lines may be an important resource for dissecting the mechanism by
      which thymosin, alone or in combination with other drugs, influences HBV-infected
      hepatocytes and/or HBV-associated carcinoma.

PMID- 9007706
TI  - Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid
      interferon in chronic hepatitis B. INTERPRED Trial Group.
AB  - BACKGROUND/AIMS: The aim of this multicentre, randomised, controlled, clinical
      trial was to evaluate the effect of prednisolone followed by lymphoblastoid
      interferon treatment in chronic hepatitis B. METHODS: Two hundred and thirteen
      patients with chronic hepatitis B were randomised to either prednisolone (2 weeks
      of 0.6 mg/kg/day, 1 week of 0.45 mg/kg/day and 1 week of 0.25 mg/kg/day) or
      matching placebo followed by a 2-week rest phase and then human lymphoblastoid
      interferon 10 MU daily for 5 days followed by 10 MU thrice weekly for 11 weeks.
      Of 200 evaluable patients, 33 (16.5%) were females, and 50 (25%) were male
      homosexuals. Thirty three patients (16.5%) had chronic persistent hepatitis, 145
      (72.5%) had chronic active hepatitis and 22 (11%) had active cirrhosis. RESULTS:
      Survival analysis disclosed statistically significant effects of prednisolone pre
      treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log
      rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). Observed HBeAg
      disappearance and HBeAg to anti-HBe seroconversion rates (placebo vs.
      prednisolone patients) were 28% vs. 44% and 23% vs. 38%. Six months after
      stopping interferon, HBV DNA was negative in 51% of prednisolone patients vs. 28%
      of placebo patients (Chi-square test statistic 6.13; p = 0.013). Prednisolone pre
      treatment tended to be more effective in patients with higher transaminase levels
      and in patients with low levels of HBV DNA. Fifteen patients (7.5%) (13 within 1
      year of follow-up) eventually lost HBsAg; 14 of these subsequently developed anti
      HBs. Interferon treatment was modified in 102 patients (51%). Three out of 22
      patients with cirrhosis (14%), one of whom received prednisolone pre-treatment,
      developed hepatic decompensation with a fatal outcome while on interferon
      treatment. CONCLUSIONS: Prednisolone pre-treatment significantly enhanced the
      treatment effect of lymphoblastoid interferon in terms of HBeAg clearance and
      seroconversion to anti-HBe. Treatment should be used with caution in patients
      with cirrhosis and avoided in patients showing signs, or with a history, of
      decompensated cirrhosis.

PMID- 9007708
TI  - Chronic hepatitis C: effect of alcohol on hepatitic activity and viral titre.
AB  - BACKGROUND/AIMS: Alcohol and the hepatitis C virus have been postulated to
      interact to adversely affect the natural history of patients with chronic liver
      disease. The aim of this study was to examine the effect of alcohol on hepatitic
      activity and serum HCV RNA levels in patients with chronic hepatitis C. METHODS:
      Forty-five consecutive patients with chronic hepatitis C were classified
      according to alcohol intake over the 3-month period preceding study entry: group
      1 (n = 23), > 10 g alcohol/day; group 2 (n = 22), < or = 10 g alcohol/day.
      Hepatitic activity and alcohol intake were assessed at study entry and, following
      moderation of alcohol intake, after a mean follow-up period of 4.4 +/- 0.2
      months. RESULTS: Hepatitic activity was significantly greater in the patients who
      consumed > 10 g of alcohol/day. Moderation of alcohol consumption in patients
      consuming > 10 g/day resulted in a significant decrease in both disease activity
      (p = 0.0002) and viral RNA titre (p = 0.018); there was no change over the study
      period in patients with a consistently low alcohol intake. CONCLUSION: The
      results support the hypotheses that, in patients with chronic hepatitis C,
      alcohol aggravates hepatic injury, increases viral load and adversely affects the
      natural history of the associated liver disease.

PMID- 9007709
TI  - Permanent response to alpha-interferon therapy in chronic hepatitis C is preceded
      by rapid clearance of HCV-RNA from serum.
AB  - BACKGROUND/AIMS: Prediction of response to interferon therapy is important in the
      management of chronic hepatitis C. Pre-therapy data are valuable but they may be
      inaccurate in some cases. Our aim was to investigate whether the biochemical and
      virological events that occur early during interferon therapy in chronic
      hepatitis C may predict the final result of the treatment. METHODS: ALT and serum
      HCV-RNA were serially measured in 53 HCV-RNA-positive patients who received a
      standard 6-month course of interferon therapy. Eleven patients with a sustained
      response, 23 who responded but subsequently relapsed and 19 who did not respond
      were studied. HCV-RNA was measured with a commercial kit (Amplicor HCV). RESULTS:
      After 4 weeks of treatment, HCV-RNA became negative in 73% of sustained
      responders, in 26% of transient responders (p = 0.02) and in none of the non
      responders. Corresponding figures after 8 weeks of therapy were 82% in sustained
      responders, 61% in transient responders and 9% in non-responders. The difference
      between sustained and transient responders at this time was not significant.
      After 4 weeks of therapy, 82% of sustained responders, 52% of transient
      responders and none of the non-responders presented normalization of alanine
      transferase. The difference between sustained and transient responders was not
      significant. Corresponding figures for normalization of alanine transferase at 8
      weeks were 82%, 96% and 0% respectively. At the end of treatment, all sustained
      responders, 70% of transient responders and none of the non-responders had
      cleared HCV-RNA from serum. CONCLUSIONS: A rapid normalization of alanine
      transferase induced by interferon therapy is associated with response, but does
      not differentiate between transient and permanent response. In contrast,
      clearance of HCV-RNA after 4 weeks of treatment, but not after 8 weeks, is
      significatively associated with sustained response. Testing for HCV-RNA early
      during interferon administration may be valuable for further decisions concerning
      therapy in patients with chronic hepatitis C.

PMID- 9007710
TI  - A histopathological study of the effects of 6-month versus 12-month interferon
      alpha-2b therapy in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Interferon therapy has been shown to have beneficial effects in
      chronic hepatitis C, but the optimal duration of treatment has not been clearly
      defined. The aims of this study were: (a) to perform a detailed histological
      comparison of the effects of a 6-month and a 12-month treatment using the Knodell
      score as well as a recently proposed grid of analysis, (b) to determine possible
      histological predictive factors of response to therapy, and (c) to attempt to
      relate histological and biochemical modifications. METHODS: Liver biopsies
      obtained before and 18 months after beginning of treatment were therefore
      compared in 26 patients treated for 6 months, and in 34 patients treated for 12
      months. RESULTS: Six months of treatment induced a significant decrease in
      periportal (p = 0.02) and intralobular (p = 0.004) hepatocyte necrosis. The same
      items were improved in the 12-month-treated patients but, in addition, portal
      inflammation (p = 0.01), bile duct lesions (p = 0.03), lymphoid aggregates (p =
      0.002) and fibrosis (p = 0.008) were also improved, according to the Knodell
      score. Low scores for fibrosis, steatosis and cholangiolar proliferation on the
      pretreatment liver biopsy could be considered predictive factors for alanine
      aminotransferase normalization at 6 months. There was no relationship between
      biochemical response and modification of fibrosis. CONCLUSION: Our results
      suggest that: (a) a decrease in fibrosis might be detected only after a 12-month
      interferon treatment, and (b) initial fibrosis, cholangiolar proliferation and
      steatosis are predictive of a lack of biochemical response. The absence of a
      relation between biochemical response and evolution of fibrosis implies that the
      evaluation of treatments in chronic hepatitis C should always include a detailed
      histopathological study.

PMID- 9007711
TI  - Infection with GB virus C (GBV-C) in patients with fulminant hepatitis.
AB  - BACKGROUND/METHODS: There appear to be hepatitis viruses other than hepatitis A,
      B, C, D and E. One of these has been proposed with a designation of GB virus C.
      Sera from 44 patients with fulminant hepatitis were tested for RNA of GB virus C
      by reverse-transcription polymerase chain reaction with nested primers deduced
      from the putative non-structural 3 (helicase) region. RESULTS: RNA of GB virus C
      was detected in three (20%) of 15 patients with hepatitis B virus infection and
      three (12%) of 25 patients without markers of hepatitis A-E virus infection.
      Overall, GB virus C RNA was detected in six (14%) of the 44 patients with
      fulminant hepatitis, at a frequency significantly higher (p < 0.001) than that in
      three (0.9%) of 326 blood donors matched for age with the patients. CONCLUSIONS:
      These results indicate a role of GB virus C in inducing fulminant hepatitis
      either by itself or in concert with the other hepatitis viruses.

PMID- 9007713
TI  - DNA ploidy study of resected hepatocellular carcinoma in cirrhotic liver.
AB  - BACKGROUND/AIMS: Results of several studies on DNA ploidy as a prognostic
      indicator in hepatocellular carcinoma are contradictory. The present study
      analysed the correlations between DNA ploidy of resected hepatocellular carcinoma
      and tumour characteristics, tumour recurrence, risk factors and survival.
      METHODS: Tumoural DNA ploidy of hepatocellular carcinomas from 37 patients with
      cirrhosis who underwent curative tumour resection was studied by flow cytometry.
      RESULTS: A diploid pattern was found in 23 hepatocellular carcinomas (62.2%) and
      an aneuploid pattern in 14 (37.8%). The tumour recurrence rate did not differ
      statistically between diploid (69.6%) and aneuploid (50%) hepatocellular
      carcinomas. The only prognostic variable with significant difference in DNA
      pattern was the histologic tumour type; the majority of non-trabecular tumours
      were aneuploid while most trabecular hepatocellular carcinomas had a diploid DNA
      pattern. Actuarial survival at 1, 2, 3 and 4 years of patients with diploid and
      aneuploid tumours was 69.6%, 40.6%, 16.2% and 0%, and 69.3%, 59.4%, 49.5% and
      32.9%, respectively (log rank p = 0.1927). CONCLUSION: These results indicate
      that DNA ploidy has no prognostic value in hepatocellular carcinoma.

PMID- 9007712
TI  - Alteration of DNA ploidy and cell nuclearity in human hepatocellular carcinoma
      associated with HBV infection.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma usually arises in cirrhotic livers as a
      complication of chronic liver disease, and may show a variable trend towards
      increasing ploidy. The aim of this study was to investigate possible associations
      between different etiological factors, particularly hepatitis B virus and
      hepatitis C virus infection, and alteration of DNA-ploidy and nuclearity of
      neoplastic hepatocytes. METHODS: DNA-ploidy, the percentage of binucleated cells
      in the total cell population and the fraction of mononucleated hepatocytes in the
      polyploid compartment were assessed by image cytometry on cellular suspensions
      obtained by fine-needle biopsy from 60 hepatocellular carcinomas in patients
      whose viral status had previously been assessed. RESULTS: Significantly higher
      DNA-ploidy values (p = 0.005), with a reduction in the percentage of binucleated
      hepatocytes (p = 0.003) and an increase in the fraction of mononucleated
      hepatocytes in the polyploid compartment (p < 0.0001), were found in
      hepatocellular carcinoma with actual or previous hepatitis B virus infection
      (including also HCV+ve patients) in comparison to those not associated with
      hepatitis B virus infection, but not when HCV+ve hepatocellular carcinomas were
      compared to HCV-ve ones. Statistically significant differences for ploidy values
      (p < 0.05), percentage of binucleated hepatocytes (p < 0.05) and fraction of
      mononucleated hepatocytes in the polyploid compartment (p = 0.003) were also
      found between hepatocellular carcinoma associated only to hepatitis B virus
      infection ("pure" hepatitis B virus cases) and those associated only to hepatitis
      C virus infection ("pure" hepatitis C virus cases). CONCLUSIONS: Hepatocellular
      carcinoma associated with a previous or actual hepatitis B virus infection shows
      a peculiar phenotypical appearance, characterized by a trend towards increasing
      ploidy and reduction of binuclearity.

PMID- 9007714
TI  - Identification of cyclin A as a molecular target of antinuclear antibodies (ANA)
      in hepatic and non-hepatic autoimmune diseases.
AB  - BACKGROUND/AIMS: Antinuclear antibodies (ANA) are a diagnostic hallmark of
      various autoimmune diseases and also of autoimmune hepatitis type 1. The
      designation ANA describes a heterogeneous group of autoantibodies. In liver
      diseases, only a few nuclear target antigens have been molecularly identified and
      characterized. Cyclins play a central role in cell cycle regulation, DNA
      transcription, and cell proliferation. Cyclin A was also identified as an
      integration site of the hepatitis B virus in a patient with hepatocellular
      carcinoma. In this study we identify cyclin A as a novel nuclear target protein
      of ANA. METHODS: Sera of patients with autoimmune hepatitis (AIH) type 1 (n =
      61), type 2 (n = 21), and type 3 (n = 39), primary biliary cirrhosis (PBC) (n =
      107), rheumatic diseases (systemic lupus erythematosus (SLE), rheumatoid
      arthritis (RA), mixed connective tissue disease (MCTD)) (n = 42) and normal
      controls (n = 100) were evaluated for ANA by indirect immunofluorescence.
      Baculovirus-generated recombinant human cyclin A protein was used for
      immunoblotting to study the prevalence of anti-cyclin A autoantibodies in these
      sera. RESULTS: Sera of patients with AIH type 1 and rheumatic diseases had ANA
      detected by indirect immunofluorescence. In AIH type 1 12/61 (20%) and in
      rheumatic diseases 6/42 (14%) were immunoblot positive for autoantibodies against
      human cyclin A. In PBC, AIH type 3 and normal control sera negative for ANA by
      immunofluorescence, anti-cyclin A autoantibodies were present in 7-9%; in AIH
      type 2 and SLE they were undetectable by immunoblot. In some sera a typical
      cyclin A immunofluorescence was observed. Anti-cyclin A antibodies recognize a 45
      and 50 kDa recombinant protein species, providing evidence for the recognition of
      at least two molecular epitopes. CONCLUSIONS: This study has identified cyclin A
      as a human autoantigen in hepatic and non-hepatic autoimmune diseases. More
      studies are required to evaluate the clinical and pathophysiological significance
      of anti-cyclin A autoantibodies. The identification of human anti-cyclin A
      autoantibodies may additionally become a valuable tool for studying the function
      and regulation of cyclin A in mammalian and human cells.

PMID- 9007715
TI  - Antibodies to E1 and E2/Protein X components of pyruvate dehydrogenase complex in
      sera of patients with primary biliary cirrhosis.
AB  - AIMS/METHODS: Using purified E1 component of pyruvate dehydrogenase complex (PDC)
      from bovine heart, we measured the levels of anti-E1 antibodies in PBC sera using
      ELISA and determined the degree of inhibition that these antibodies exerted on E1
      enzyme activity. We also estimated levels of anti-E2/Protein X (Pro-X) antibodies
      in PBC sera using purified E2 and Pro-X of PDC which were copurified with E1.
      RESULTS/CONCLUSIONS: Anti-E1 antibodies were detected in 87.5% (35/40) of PBC
      sera. Some of these sera inhibited E1 enzyme activity but inhibition did not
      correlate with levels of anti-E1 antibodies. A high positive correlation (r =
      0.918) was found between levels of anti-E1 and anti-E2/Pro-X antibodies,
      suggesting that anti-PDC antibody production was stimulated by PDC itself. Levels
      of IgG class anti-E2/Pro-X antibodies were significantly higher in sera of
      symptomatic PBC patients than in those of asymptomatic PBC patients. It was also
      found that patients who were positive for only IgM class anti-E2/Pro-X antibodies
      had early-stage PBC.

PMID- 9007716
TI  - Increased intercellular adhesion molecule-1 serum concentration in cholestasis.
AB  - BACKGROUND/AIMS: Increase of serum levels of the soluble intercellular adhesion
      molecules in patients with the cholestatic liver diseases primary biliary
      cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been
      thought to indicate activation of the immune system and the grade of the
      inflammatory process. In hepatitis and cholestatic diseases, expression of
      adhesion molecules was found on the surface of bile duct epithelia and
      hepatocytes. MATERIALS AND METHODS: Serum levels of sICAM-1 in patients with
      intrahepatic cholestasis in PBC (n = 42) and extrahepatic cholestasis (n = 18)
      due to choledocholithiasis were investigated. sICAM-1 levels and "classical"
      cholestasis parameters as alkaline phosphatase (ALP), gamma-glutamyl
      transpeptidase (gamma-GTP) and bilirubin levels were compared. Furthermore, sICAM
      1 concentrations and "classical" cholestasis parameters were analysed before and
      after therapy with ursodeoxycholic acid (UDCA). In addition, sICAM-1 was detected
      in serum and bile fluid of four patients with cholestasis due to
      choledocholithiasis. Soluble ICAM-1 levels in sera and, if accessible, in bile
      fluids were determined using a commercially available ELISA system. Statistics
      were done by Wilcoxon's signed rank exact test and Spearman's rank correlation
      test. Sensitivity and specificity of cholestasis parameters and sICAM-1
      concentrations was analysed by receiver operating characteristic (ROC) curves.
      RESULTS: Increased sICAM-1 serum concentrations in a similar range were found in
      patients with PBC (range 251-2620 micrograms/l; median 966 micrograms/l) as well
      as in patients with extrahepatic cholestasis (257-2961 micrograms/l; median 760
      micrograms/l) compared to healthy controls (n = 12; 220-500 micrograms/l; median
      318 micrograms/l). sICAM-1 levels correlated significantly to histological stage
      I to IV (p < 0.001), ALP (range 107-1877 U/l; median 545 U/l; r = 0.496, p =
      0.0008), bilirubin (range 0.3-26 mg/dl; median 0.8 mg/dl; r = 0.52; p < 0.0004)
      and gamma-GTP levels (range 43-705 U/l; median 221 U/l; r = 0.36; p = 0.02) in
      PBC patients. In PBC patients a histological stage III or IV (n = 21) could be
      predicted with high sensitivity (95%) and specificity (85%) if sICAM-1 levels
      were above 840 micrograms/l. After treatment of PBC patients with UDCA, sICAM-1
      levels decreased significantly with decline of other "classical" cholestasis
      parameters. Increased sICAM-1 levels (range 257-2961, median 745 micrograms/l) in
      extrahepatic cholestasis correlated also significantly with serum concentrations
      of bilirubin (r = 0.8; p < 0.01; range 0.3-19.7, median 1.6 mg/dl), gamma-GTP (r
      = 0.55; p = 0.03; range 33-1401, median 179 U/l) and ALP (r = 0.61; p = 0.1;
      range 110-1378, median 562 U/l). sICAM-1 was detectable in bile fluid (264-919
      micrograms/l) of four patients with extrahepatic cholestasis and nose-biliary
      catheterisation. CONCLUSIONS: sICAM-1 concentrations were found to discriminate
      between histological stage I/II and stage III/IV of PBC with higher sensitivity
      and specificity than "classical" cholestasis parameters. Increased serum
      concentrations for sICAM-1 in intra- and in extrahepatic cholestasis and
      detection of sICAM-1 in the bile may indicate that sICAM-1 is eliminated through
      the bile. In other words, not only increased synthesis but also decreased
      elimination may be responsible for increased sICAM-1 serum levels in patients
      with cholestatic liver diseases.

PMID- 9007718
TI  - Lysosomal enzyme activities in gallbladder mucosa of gallstone-free subjects and
      patients with gallstones.
AB  - BACKGROUND/AIMS: Gallstone patients have a reduced cellular lysosome content in
      the gallbladder mucosa cells compared with gallstone-free subjects. The purpose
      of the study was to further evaluate the possible role of lysosomes in the
      pathogenesis of cholesterol gallstone formation in humans. METHODS: Lysosomal
      enzyme activities were assayed in gallbladder mucosa and for comparison in liver
      specimens of 19 gallstone-free subjects and 24 gallstone patients undergoing
      cholecystectomy. RESULTS: Gallstone patients had 25-50% lower activities of the
      lysosomal proteases cathepsin B, D and L in their gallbladder mucosa compared
      with gallstone-free subjects. The activity of acid phosphatase also tended to be
      decreased in gallstone patients. The liver lysosomal enzyme activities were not
      significantly different between the two groups. CONCLUSIONS: The results show
      that gallstone patients have diminished lysosomal enzyme activities in the
      gallbladder mucosa, a finding which may be related to decreased intracellular
      degradation of proteins and/or mucin in the mucosal cells. This may lead to a
      higher concentration of mucin in gallbladder bile and thus an increased risk of
      precipitation of cholesterol crystals and gallstone formation.

PMID- 9007719
TI  - Systemic haemodynamic changes in patients with cystic fibrosis with and without
      chronic liver disease.
AB  - BACKGROUND/AIMS: There are well-documented systemic haemodynamic changes
      associated with chronic liver disease. Patients with cystic fibrosis may develop
      chronic liver disease, but it is not known whether these systemic haemodynamic
      changes develop and, if they do, whether they are influenced by the associated
      chronic lung disease. We therefore undertook a study to document the circulatory
      status of cystic fibrosis patients with and without chronic liver disease.
      METHODS: Fifty-six subjects with cystic fibrosis were studied. Systemic
      haemodynamic and pulmonary parameters, in sub-groups both with (LD) and without
      (NLD) liver disease, were measured at rest and during measured exertion. Cystic
      fibrosis-related chronic liver disease was diagnosed using previously validated
      ultrasound criteria. Patients underwent assessment at rest and in the fourth
      minute of seated bicycle exercise at 25W. Heart rate (ECG), blood pressure
      (semiautomated sphygmomanometer), aortic blood velocity (pulsed Doppler
      suprasternal probe), arterial oxygen saturation (pulse oximeter) and respiratory
      variables (pneumotachometer with expired gas analysis by an automatic system)
      were measured. RESULTS: A complete data set was available for 45 patients (22 LD)
      at rest and 40 patients (19 LD) on exercise. The patients were well matched for
      age, sex, height, weight, and pulmonary function. Patients with chronic liver
      disease had a hyperkinetic circulation while ventilatory variables before and
      during exercise were similar for the two groups. There was evidence that the
      circulatory changes were exacerbated by both deteriorating hepatic and pulmonary
      function. CONCLUSIONS: Cystic fibrosis patients with chronic liver disease have a
      hyperdynamic circulation similar to that documented in other forms of chronic
      liver disease. These circulatory changes are exacerbated by deteriorating hepatic
      and pulmonary function.

PMID- 9007717
TI  - Single or multiple dose ursodeoxycholic acid for cholestatic liver disease:
      biliary enrichment and biochemical response.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary
      biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts
      partly by reducing the intestinal absorption of hydrophobic endogenous bile salts
      and is poorly absorbed from the intestine, a multiple dose regimen has been
      advocated. Single dose treatment, on the other hand, may improve compliance. AIM:
      The effects of a single or multiple dose regimen on liver enzymes and serum and
      biliary bile salts composition were evaluated. METHODS: Twenty-seven patients (19
      PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg-1 day-1) in a
      single dose at bed time (n = 13) or in three divided gifts with meals (n = 14)
      over 3 months. Five patients had both treatment regimens in random order with a 1
      month wash-out period in between. RESULTS: Liver biochemistry equally improved in
      both groups. Biliary enrichment (% UDCA of total bile salts, mean +/- SEM) was
      40.1 +/- 2.4 in the single dose group vs 40.8 +/- 2.8 in the multiple dose group
      (p = NS) and was positively correlated with biochemical improvement (AP: r =
      0.47, p = 0.02; GGT: r = 0.58, p = 0.002; ASAT: r = 0.67, p = 0.002; ALAT: r =
      0.52, p = 0.01). Biochemical improvement was not correlated with the
      concentration or %UDCA in serum. Patients participating in the cross-over design
      had comparable biochemical response and biliary %UDCA during both regimens.
      CONCLUSION: Single and multiple dose UDCA have similar effects on liver
      biochemistry and biliary enrichment in cholestatic liver disease. Biochemical
      improvement appears to be related to biliary (but not serum) enrichment with
      UDCA.

PMID- 9007720
TI  - Acute haemodynamic changes after oral carvedilol, a vasodilating beta-blocker, in
      patients with cirrhosis.
AB  - BACKGROUND/AIMS: Combinations of beta-blockers and vasodilators have been
      assessed for their ability to lower portal pressure and so prevent variceal
      haemorrhage. However, reservations have been raised particularly with respect to
      renal function and perfusion after the use of these medicines in patients with
      chronic liver disease. We studied the acute effects of carvedilol, a new
      vasodilating beta-blocker which combines non-selective beta-blockade with alpha-1
      receptor antagonism, upon the haemodynamics of patients with cirrhosis. METHODS:
      Sixteen patients completed the study which measured the changes approximately 1 h
      after the administration of 25 mg oral carvedilol. RESULTS: The hepatic venous
      pressure gradient fell from 16.7 +/- 0.9 to 13.6 +/- 1.0 mmHg (p < 0.00001),
      accounted for largely by reductions in the wedged hepatic venous pressure.
      Despite this, the azygos blood flow did not change. There was a significant fall
      in mean arterial pressure (94.8 +/- 4.4 cf. 84.6 +/- 4.3 mmHg; p = 0.0001), which
      was particularly apparent in the diastolic blood pressure of those patients with
      ascites. The heart rate only fell significantly in the ascitic subjects. No
      significant changes occurred in the cardiac output or systemic vascular
      resistance. Unilateral renal vein flow as measured by the reverse thermodilution
      technique remained constant. CONCLUSIONS: Carvedilol is therefore a potent acute
      portal hypotensive agent which does not appear to compromise renal perfusion.
      However, patients with ascites are at greater risk of its systemic hypotensive
      action.

PMID- 9007721
TI  - Renal and neurohormonal changes following simultaneous administration of systemic
      vasoconstrictors and dopamine or prostacyclin in cirrhotic patients with
      hepatorenal syndrome.
AB  - BACKGROUND/AIMS: Intravenous ornipressin in cirrhotic patients with hepatorenal
      syndrome causes marked improvement of systemic hemodynamics and suppression of
      plasma renin and norepinephrine but only moderate improvement of renal function.
      This study was designed to investigate whether these beneficial effects could be
      enhanced by the simultaneous administration of dopamine. The renal effects of the
      i.v. infusion of norepinephrine plus prostacyclin in patients with hepatorenal
      syndrome were also assessed. METHODS: Renal plasma flow, glomerular filtration
      rate, free water clearance, sodium excretion and the plasma levels of renin and
      norepinephrine were measured in baseline conditions and during the administration
      of ornipressin (6 i.u./h) and ornipressin (6 i.u./h) plus dopamine (2
      micrograms/kg.min) in nine patients with hepatorenal syndrome. Five additional
      patients with hepatorenal syndrome were studied prior to and following the
      administration of norepinephrine (0.45 +/- 0.1 microgram/kg.min) and
      norepinephrine (0.85 +/- 0.2 microgram/kg.min) plus prostacyclin (5 ng/kg.min).
      RESULTS: Despite a significant increase in arterial pressure and marked
      suppression of plasma renin activity during ornipressin and ornipressin plus
      dopamine administration, no significant improvement in renal function was
      observed. Norepinephrine and norepinephrine plus prostacyclin also failed to
      increase renal perfusion and glomerular filtration rate. CONCLUSIONS: The
      combined administration of systemic vasoconstrictors (ornipressin or
      norepinephrine) and vasodilators (dopamine or prostacyclin), at the doses used in
      the current study and for a short period of time, does not improve renal function
      in cirrhotic patients with hepatorenal syndrome. The current study does not
      confirm a potential role for ornipressin in the treatment of hepatorenal
      syndrome.

PMID- 9007722
TI  - Bilioenteric anastomosis reverses hyperkinetic circulation in bile duct-ligated
      cirrhotic rats.
AB  - BACKGROUND/AIMS: The chronic bile duct-ligated rat is used to study hemodynamic
      changes in cirrhosis but suffers from total biliary obstruction and deep
      jaundice. The extent of reversibility of hemodynamics and histology following
      bile flow reconnection is controversial. We aimed to characterize the
      hemodynamics and histology of bile duct-ligated cirrhotic rats in which bile flow
      was reconnected by a Roux-en-y choledochojejunostomy. METHODS: Operations created
      four groups: double sham (control), bile duct ligated, and two reconnected
      groups. Cardiac index and regional blood flows were measured by radioactive
      microspheres 4 weeks following the last operation in the first three groups and 8
      weeks afterwards in the second reconnected group. Liver histology was assessed by
      a computer-aided scoring program. RESULTS: Cardiac index, mean arterial pressure,
      and systemic vascular resistance in the reconnected groups were different from
      bile duct-ligated rats and returned to control values. Portal pressures in the
      reconnected groups (4-weeks, 10.0 +/- 0.5 and 8-week, 9.7 +/- 0.6 mmHg) were
      significantly lower than in bile-duct-ligated rats (13.7 +/- 0.6) but remained
      elevated compared to controls (7.0 +/- 0.3). Portal pressure in the reconnected
      rats was correlated with cardiac index and mesenteric blood flow, r = 0.66 and r
      = 0.45, respectively. Liver histology was improved in the reconnected rats, with
      decreased bile duct proliferation, fibrosis and apoptosis. CONCLUSIONS: We
      conclude that many of the histological features of secondary biliary cirrhosis
      are reversible after bilioenteric anastomosis. Furthermore, the hyperdynamic
      circulation is also largely reversible and is related to the degree of portal
      hypertension.

PMID- 9007723
TI  - Ontogenic expression of the Na(+)-independent organic anion transporting
      polypeptide (oatp) in rat liver and kidney.
AB  - BACKGROUND/AIMS: A cDNA (2.7 kb) encoding a rat liver basolateral Na(+)
      independent organic anion transporter (oatp) has recently been cloned. The aim of
      the present study was to clarify the mechanisms of bile formation during
      development. METHODS: The ontogenic expression of oatp was examined by northern
      blot analysis and in situ hybridization in rat liver. The expression of oatp in
      the kidney was also studied in parallel. RESULTS: In the liver, a 2.5 kb oatp
      mRNA was first detected in the fetus on day 16 of gestation. The amount of this
      oatp mRNA remained stable during the perinatal period and increased dramatically
      after weaning. Other transcripts probably corresponding to oatp-related mRNAs
      also display a late expression pattern in the perinatal period. In contrast,
      Na+/taurocholate transporting polypeptide (Ntcp) mRNA was first detected on day
      20 of gestation. By in situ hybridization, oatp mRNA was localized into
      hepatocytes and distributed without lobular heterogeneity. In the kidney, a
      single 2.4 kb oatp transcript was detected from birth to adult age. This
      transcript was exclusively distributed in the epithelial cells of the proximal
      tubules localized in the kidney cortex and the outer medulla. CONCLUSIONS: These
      results indicate that oatp undergoes a time-related expression in rat liver and
      kidney during development and that its gene transcription precedes Ntcp gene
      transcription in the liver. The delayed expression of oatp at the perinatal
      period may explain in part the immaturity of bile formation and the physiological
      neonatal cholestasis.

PMID- 9007724
TI  - Interleukin-6 induces proliferation of rat hepatocytes in vivo.
AB  - BACKGROUND/AIMS: The aim of this study was to assess the effect of interleukin-6
      (IL-6) on the proliferation of hepatocytes and to study the interaction between
      IL-6 and hepatocyte growth factor (HGF) in vivo. METHODS: IL-6 was injected at a
      dose of 200 micrograms/mg subcutaneously into rats every day for 14 days. Liver
      and blood samples were obtained at 1, 3, 7 and 14 days during IL-6
      administration. Hepatocyte proliferative activity of sera was measured using 3H
      thymidine incorporation into cultured rat hepatocytes. To evaluate the
      proliferative activity of the hepatocytes in tissue sections, hepatic DNA content
      and immunostaining of the liver tissue sections for proliferating cell nuclear
      antigen (PCNA) were performed. Plasma HGF levels were measured using specific
      EIA. In addition, total RNA was extracted from the liver and expression of HGF
      mRNA was detected by RT-PCR. RESULTS: The DNA contents of liver taken from IL-6
      treated rats were increased during IL-6 administration compared with untreated
      rats. Sera taken from IL-6-treated rats at various intervals during
      administration also significantly increased 3H-thymidine incorporation by
      cultured rat hepatocytes compared with sera from untreated rats, suppressing 3H
      thymidine incorporation at day 1 and 3 by anti-HGF antibody. IL-6 itself did not
      increase 3H-thymidine incorporation. Increased expression of PCNA in these
      hepatocytes was noted from 1 day after IL-6 administration, and at 14 days, the
      number of PCNA-positive cells was sevenfold greater than in the livers of
      untreated rats. However, plasma HGF levels showed a peak at day 1, decreased
      gradually from day 3, and became undetectable by day 14. HGF mRNA expression in
      livers of IL-6-treated rats was suppressed from day 3 to day 14 of IL-6
      administration. CONCLUSIONS: These data show that IL-6 induces an early phase of
      liver cell growth in vivo and suggest that an increase level of HGF mediates this
      effect.

PMID- 9007725
TI  - A novel mechanism of murine hepatocyte death inducible by concanavalin A.
AB  - BACKGROUND: Concanavalin A (Con A) is a plant lectin that polyclonally activates
      T-cells. When given intravenously to mice it induces a selective liver failure.
      Hepatotoxicity following Con A administration involves the systemic release of
      tumor necrosis factor. METHODS: We used primary murine hepatocyte cultures to
      investigate mechanisms of hepatocytotoxicity related to this animal model of
      inflammatory liver failure. RESULTS: Con A was directly toxic for cultured
      hepatocytes. This toxicity did not require additional cytokines or the presence
      of T cells. Cytotoxicity due to Con A involved specific binding of the lectin to
      mannosyl cell surface receptors, but no internalization. Other structurally
      similar lectins lacked such an in vitro hepatocytotoxicity. Con A induced
      initially reversible alterations of the morphology that were different from the
      ones caused by classical hepatotoxins. Con A-induced cell death was highly
      specific for murine hepatocytes. It was neither apoptotic by morphology nor did
      it involve DNA fragmentation. In addition, Con A caused a fall in cellular total
      glutathione content and an increase in transcriptional activity. Stabilization of
      microtubules by taxol completely protected cells from the lectin. CONCLUSIONS:
      Stimulation of hepatocytes with Con A elicits a novel mechanism of cytotoxicity
      due to inappropriate excessive stimulation of membrane receptors and subsequent
      disturbance of the cytoskeleton.

PMID- 9007726
TI  - In vivo assessment of hepatic alterations following gadolinium chloride-induced
      Kupffer cell blockade.
AB  - BACKGROUND/AIMS: In recent years, Gadolinium chloride (GdCl3), a rare earth
      metal, has frequently been used to study the role and function of Kupffer cells
      under physiological and pathological conditions. This study was performed to
      elucidate the consequences of GdCl3-induced Kupffer cell blockade for hepatic
      microcirculation, hepatocellular function and integrity. METHODS/RESULTS: Using
      intravital fluorescence microscopy, we studied the hepatic microcirculation of
      rats pretreated with either GdCl3 (n = 12; 10 mg/kg; 1 ml i.v. for 2 d) or saline
      (n = 9; 1 ml). The GdCl3-treated animals revealed a significantly lower
      phagocytic activity of Kupffer cells when compared to controls. Concomitantly,
      GdCl3-treatment resulted in a pronounced rise of serum cytokine activity (tumor
      necrosis factor-alpha; interleukin-6). The hepatic microvascular perfusion was
      characterized by a moderate increase in the number of non-perfused sinusoids
      accompanied by a reduction of bile flow. In addition, GdCl3-treatment caused a
      slight increase in liver enzyme activity (< 200 U/l) (aspartate aminotransferase
      and alanine aminotransferase) with no substantial parenchymal tissue injury
      (light microscopy). The groups did not differ in concentrations of circulating
      endotoxin (GdCl3-treatment: 0.044 +/- 0.042 ng/ml; controls: 0.052 +/- 0.014
      ng/ml). CONCLUSIONS: We conclude that hepatic alterations following Kupffer cell
      blockade with GdCl3 may possibly be the consequence of cytokine release as a
      response to the phagocytic challenge of GdCl3-aggregates. If used for Kupffer
      cell blockade, the hepatic alterations following GdCl3-treatment described in the
      present study should be taken into consideration.

PMID- 9007727
TI  - Reactivated fulminant hepatitis B virus replication after bone marrow
      transplantation: clinical course and possible treatment with ganciclovir.
AB  - A female chronic hepatitis B virus carrier (HBV-DNA negative) suffered from
      simultaneous hepatitis B virus and cytomegalovirus reactivation after in vivo T
      cell depletion preceding transplantation of an in vitro T cell depleted marrow
      graft for treatment of acute leukaemia. Interstitial pneumonia developing after
      bone marrow transplantation was successfully treated with ganciclovir (day 13
      until day 46). The initially unnoticed extensive hepatitis B virus replication
      finally led to clinical hepatitis (day 85) and liver failure (day 96). Liver
      transplantation was performed, but the patient died from septicaemia.
      Retrospective analysis of hepatitis B virus DNA revealed that the HBV replication
      started immediately after T cell depletion and was completely suppressed during
      ganciclovir administration. Screening for HBV-DNA seems to be mandatory in
      comparable cases, and antiviral chemotherapy should be seriously considered.

PMID- 9007728
TI  - Immune thrombocytopenia and alpha-interferon therapy.
AB  - Thrombocytopenia is often found in patients with liver diseases, especially due
      to congestive splenomegaly caused by portal hypertension. Immune thrombocytopenia
      has been described rarely, and it seems to be especially associated with
      hepatitis C virus, which has been described as having a particular interaction
      with the immune system contributing to the induction of autoimmunity.
      Interferons, on the other hand, because of their immunomodulatory properties, are
      able to induce or exacerbate autoimmune diseases. Mild thrombocytopenia is a
      common adverse effect of interferon therapy. Severe life-threatening
      thrombocytopenia is extremely rare. We report two cases of severe immune
      thrombocytopenia in patients with chronic hepatitis C, probably induced by alpha
      interferon. Bone marrow aspirate and elevated platelet-associated IgG antibodies,
      determined by indirect immunofluorescence, were suggestive of immune
      thrombocytopenia. None of the patients had any clinical sign of autoimmune
      syndrome, including arthritis, serositis, Sicca syndrome, vasculitis, thyroid
      abnormalities and others. Cryoglobulins and rheumatoid factor were tested and
      were undetectable. The patients' histories of exposure to alpha-interferon and
      the exclusion of other causes are most consistent with drug-induced immune
      thrombocytopenia. After alpha-interferon withdrawal, thrombocytopenia was treated
      successfully with prednisolone and immunoglobulins. Response to treatment was
      consistent with the diagnosis of alpha-interferon-induced immune thrombocytopenia
      and peripheral consumption of platelets.

PMID- 9007729
TI  - Role of oral contraceptives in the growth of a multilobular adenoma associated
      with a hepatocellular carcinoma in a young woman.
AB  - BACKGROUND: The occurrence of hepatocellular neoplasms is frequently reported in
      young females. The role of oral contraceptives in the development of these tumors
      is considered. METHODS: A 14-cm tumor was diagnosed in a 24-year-old female who
      had been taking the contraceptive pill for the last 3 years. Numerous blocks of
      this lesion were histologically and immunohistochemically analyzed. Some
      fragments of the lesion were snap-frozen in order to search for sex hormonal
      receptors and hepatitis B and C virus. RESULTS: On histological examination, the
      tumor was found to be a hepatocellular, multilobular adenoma with small foci of
      hepatocellular carcinoma. Neither hepatitis B virus nor hepatitis C virus was
      found in serum or in the tumor. Nuclear estrogen receptors and progesterone
      receptors were detected by immunohistochemical analysis in both the adenoma and
      the carcinoma, but only progesterone receptors were detected by a radio-ligand
      binding assay in the tumor. CONCLUSION: This finding suggests that the
      contraceptive pill may stimulate the growth of hepatocellular, multilobular
      adenomas through the binding of hormonal compounds to their specific receptors
      within tumoral cells.

PMID- 9007731
TI  - Assignment of the human organic anion transporting polypeptide (OATP) gene to
      chromosome 12p12 by fluorescence in situ hybridization.
AB  - BACKGROUND/AIMS: The organic anion transporting polypeptide (OATP) of human liver
      mediates the basolateral hepatocellular uptake of numerous cholephilic anions and
      steroidal compounds. The aim of this study was to clone the human OATP gene and
      to map its chromosomal localization by fluorescence in situ hybridization.
      METHODS: A polymerase chain reaction-amplified fragment of the human OATP gene
      was used to isolate a genomic OATP clone from a P1-derived artificial chromosome
      human genomic library. Human metaphase chromosomes were hybridized with
      digoxigenin-labeled DNA from the genomic OATP clone and incubated in
      fluoresceinated antidigoxigenin antibodies for in situ detection of specific
      hybridization signals. RESULTS: Sequence analysis revealed that the isolated P1
      derived artificial chromosome clone contained a large portion of the human OATP
      gene. Fluorescence in situ hybridization of human chromosomes with the genomic
      OATP clone resulted in the specific labeling of the OATP gene on the short arm of
      chromosome 12 at band 12p12. CONCLUSIONS: Mapping of a genomic OATP clone to
      chromosome 12p12 represents a first step towards the molecular characterization
      of the human OATP gene. While no liver disease has so far been associated with
      cytogenetic abnormalities of the short arm of chromosome 12, the genomic OATP
      sequence provides the basis for studies on gene structure and on the tissue
      specific regulation of OATP gene expression.

PMID- 9007730
TI  - GBV-C/HGV is not the major cause of autoimmune hepatitis.
AB  - Recently, GBV-C and HGV-two isolates of the same new flavivirus-were identified
      in serum samples of patients with indeterminate hepatitis and posttransfusion
      hepatitis, respectively. The pathogenic relevance of these viruses is still
      uncertain. As viral infections are presumed to trigger autoimmune processes, we
      investigated GBV-C in autoimmune hepatitis as well as in cryptogenic hepatitis,
      and compared the prevalences to patients with chronic viral hepatitis and those
      of blood donors. We found only a slightly higher prevalence of the virus in
      cryptogenic (12%) and autoimmune hepatitis type I-III (6.7%, 10%, and 12.5%)
      compared to blood donors (4.7%). In contrast, patients with viral hepatitis B, C,
      and D were more frequently infected with GBV-C (16%, 20%, 36%). These results
      suggest that GBV-C is not a major cause for inducing autoimmunity and leading to
      autoimmune hepatitis. We analyzed the nucleic acid sequences of a representative
      number of GBV-C positive patients (24/42) and found a broad range of nucleotide
      similarity in the NS3 helicase region (74-100%) among the isolates and the
      prototype sequences. However, we could not identify a specific sequence, which
      would point to a certain strain or subtype of the virus associated with
      autoimmune or cryptogenic liver disease.

PMID- 9007732
TI  - The application of magnetic resonance spectroscopy to the study of hepatic
      encephalopathy.

PMID- 9007733
TI  - Platelet-associated immunoglobulin G, thrombocytopenia and response to interferon
      treatment in chronic hepatitis C.

PMID- 9007735
TI  - Severe acute hepatitis associated with morphazinamide therapy.

PMID- 9007734
TI  - Viral hepatitides and idiopathic (autoimmune) thrombocytopenic purpura. Is there
      any relationship?

PMID- 9007736
TI  - In vitro selection of hairpin ribozymes.

PMID- 9007737
TI  - A history of tuberculosis infection.

PMID- 9007738
TI  - Cognitive deficits in Parkinson's disease.
AB  - Neuropsychological investigations of patients with Parkinson's disease have shown
      specific impairments even in the early stages of the disease, which include
      deficit of behavioural regulation in sorting or planning tasks, defective use of
      memory stores, and impaired manipulation of internal representation of
      visuospatial stimuli. These deficits, reported in a disease which predominantly
      involves subcortical structures, have drawn attention to a potential role of the
      basal ganglia in cognitive processes. Given the modulatory role of the basal
      ganglia, these disorders might result from more fundamental deficits concerning
      the allocation of attentional resources, the temporal organization of behaviour,
      the maintenance of representations in working memory or the self-elaboration of
      internal strategies, all of which resemble dysfunctions of processes that are
      commonly considered to be controlled by the frontal lobes. This suggests a
      functional continuity or complementarity between the basal ganglia and
      association areas of the prefrontal cortex. The recent description in primates of
      segregated loops that interconnect discrete regions of the caudate nucleus to the
      dorsolateral and orbitofrontal regions of the prefrontal cortex via the thalamus
      may give some support to this hypothesis. Alternatively, degeneration of the
      ascending cholinergic and catecholaminergic neuronal systems may contribute, at
      least in part, to the occurrence of this frontal-lobe-like symptomatology
      associated with Parkinson's disease.

PMID- 9007739
TI  - Drug therapy for acquired pendular nystagmus in multiple sclerosis.
AB  - Acquired pendular nystagmus (APN) is regularly accompanied by oscillopsia and
      impairment of static visual acuity. Therapeutic approaches to APN remain
      controversial, and there is no generally accepted therapeutic approach. We tested
      14 patients who had suffered from APN caused by multiple sclerosis for several
      years; 12 patients presented with fixational pendular nystagmus (increasing
      during fixation) and 2 with spontaneous pendular nystagmus. All 11 patients with
      fixational pendular nystagmus who were given memantine, a glutamate antagonist,
      experienced complete cessation of the nystagmus. In contrast, scopolamine caused
      no (6 of 8) or only a minor (10-50%) reduction of the nystagmus (2 of 8). It was
      concluded that memantine is a safe treatment option for APN.

PMID- 9007740
TI  - Reversible dementia in elderly patients referred to a memory clinic.
AB  - Dementia has a reversible cause in some cases, and these should be diagnosed
      without over-investigating the many patients with irreversible disease. We
      prospectively studied the prevalence of reversible dementia in a memory clinic,
      determined the added value of investigations compared with clinical examination
      and assessed the outcome of treatment of potentially reversible causes by
      measuring (1) cognition, (2) disability in daily functioning, (3) behavioural
      changes and (4) caregiver burden. Two hundred patients aged 65 years and over
      were examined, using the CAMDEX-N. If they were demented, the probable cause was
      diagnosed clinically and confirmed or excluded by a standard set of
      investigations, which were done in all patients. Of the patients, 170 (mean age
      79.2 years) were demented; 31 were treated for potentially reversible causes. At
      follow-up after 6 months, no patients showed complete reversal of dementia. Five
      patients improved on clinical impression, but only one on clinical measurement.
      Thirty patients were cognitively impaired, but not demented; seven were treated.
      Judged clinically, three patients improved, but on assessment only one did so;
      she recovered completely. Blood tests often produced diagnostic results that were
      not expected clinically, but electroencephalography and computed tomography of
      the brain did not. None of the investigations had an effect on outcome of
      dementia after treatment. We conclude that in elderly patients referred to a
      memory clinic, the prevalence of reversible dementia is of the order of 1%, if
      outcome after treatment is assessed by a standardized measurement. We recommend
      blood tests in all patients, to detect not only metabolic causes of dementia but
      also co-morbidity possibly worsening the dementia. Other investigations can be
      performed on clinical indication. Clinical evaluation remains the mainstay of
      diagnosis in dementia.

PMID- 9007741
TI  - Distal muscular dystrophy of Miyoshi type. Report of two cases and review of the
      literature.
AB  - Miyoshi myopathy (MM) is a rare distal myopathy that mainly occurs in Japan. And
      that is characterized by prominent involvement of the gastrocnemius muscles. Here
      we report two patients, brother and sister, from a German family. Onset of the
      disease was at the age of 20 and 22 years, respectively. In both siblings, there
      was an early and predominant involvement of the gastrocnemius muscles. Creatine
      kinase activity was elevated 37- to 95-fold above normal. Electromyography
      revealed fibrillations, positive sharp waves and a myopathic pattern,
      particularly in the distal muscles of the lower limbs. Histology of the
      gastrocnemius muscles showed myopathic changes consistent with muscular
      dystrophy. Occurrence in these two siblings but in no other family members was
      indicative of an autosomal-recessive inheritance. Our report indicates that MM
      may also be found in Germany, and that it should be considered in the
      differential diagnosis of distal myopathies.

PMID- 9007742
TI  - Blink reflex in patients with Wallenberg's syndrome.
AB  - Knowledge of the neural circuits involved in Wallenberg's syndrome (WS) is
      incomplete. Study of the blink reflex (BR) in patients with WS can help in
      reaching a better understanding of the physiopathology underlying clinical
      symptoms and may help in the prediction of clinical outcome. We evaluated the BR
      in response to supraorbital nerve electrical stimuli in 20 patients with WS. All
      patients were studied within the 1st week after onset of symptoms, and 10 of them
      were also studied repeatedly during a follow-up period of 3-12 months. At the
      first examination the long latency bilateral responses (R2 and R2c) to
      stimulation of the supraorbital nerve of the affected side were absent in 11,
      delayed in 4, and normal in 5 patients. At follow-up, there was a normalization
      of the BR in all patients who had absent or delayed responses at the first
      examination except for one patient whose responses remained absent at the 9th
      month. Late responses elicited on the side of the lesion by stimulation of the
      non-affected supraorbital nerve were normal in all but one patient. This patient
      died from cardiorespiratory arrest within the 1st month of the illness. One
      patient with normal BR responses also died in the acute phase. The BR is abnormal
      in most patients with acute WS and tends to normalize in a mean period of 7
      months. BR pattern is not a predictor of early fatal complications in patients
      with this syndrome.

PMID- 9007744
TI  - Familial Lafora body disease of late onset: report of four cases in one family
      and a review of the literature.
AB  - Lafora body disease is one cause of progressive myoclonus epilepsy. It typically
      presents in the second decade with generalized seizures, myoclonus and then
      intellectual decline. Death is usual within 10 years. Diagnosis may be made by
      biopsy of skin, muscle, liver or brain. We present four siblings who were normal
      until their mid-twenties, but then developed intellectual decline, followed by
      myoclonus. Although a rare form of Lafora body disease has been described that
      follows a more benign course, may be of later onset, and whose pathology is
      subtly different, this family is so far unique in terms of the late presentation
      of otherwise typical Lafora body disease.

PMID- 9007743
TI  - A comparison of brain biopsy and CSF-PCR in the diagnosis of CNS lesions in AIDS
      patients.
AB  - Twenty patients with AIDS who had intracranial lesions underwent both brain
      biopsy and cerebrospinal fluid (CSF) examination to compare histological
      diagnosis with the polymerase chain reaction (CSF-PCR) for the identification of
      infectious agents. CSF-PCR was performed for herpes simplex virus, varicella
      zoster virus, cytomegalovirus (CMV), JC virus (JCV), Epstein-Barr virus (EBV),
      Toxoplasma gondii and Mycobacterium tuberculosis. A definitive diagnosis was
      obtained by brain biopsy in 14 patients (2 with astrocytoma, 12 with brain
      infection). CSF-PCR was positive for EBV DNA in 3 of 3 cases of primary cerebral
      lymphoma, positive for JCV DNA in 6 of 7 biopsy-proven (and one autopsy-proven)
      cases of progressive multifocal leukoencephalopathy (PML). CSF-PCR was positive
      for CMV DNA in one biopsy-proven and one autopsy-proven case of CMV encephalitis
      (the former also had PML) and positive for M. tuberculosis DNA in one case of
      tuberculous encephalitis. None of the five toxoplasmic encephalitis cases (one
      definite, four presumptive) were T. gondii DNA positive. There was close
      correlation between histology and CSF-PCR for CMV encephalitis, PML and PCL.
      Antitoxoplasma therapy affected the sensitivity of both histological and CSF-PCR
      methods.

PMID- 9007745
TI  - Severe stenosis of the internal carotid artery is not associated with borderzone
      infarcts in patients randomised in the European Carotid Surgery Trial.
AB  - Borderzone infarcts are usually regarded as being caused by low cerebral blood
      flow distal to a severely stenosed or occluded artery, particularly the internal
      carotid artery. To explore this hypothesis we have related borderzone infarction,
      defined by CT both in the classical way and by taking into account the variable
      extent of the territory of the blood supply of the cerebral arteries, to the
      severity of any disease of the symptomatic artery in 384 patients in the European
      Carotid Surgery Trial in whom a scan showing infarction was available. Although
      there was a tendency for borderzone infarction to occur more often distal to
      severe carotid disease, this was not significant, and many cases of borderzone
      infarcts occurred in patients with mild or moderate carotid disease. Therefore,
      the topography of infarction on CT cannot be used to imply a particular
      pathophysiology based on the severity of disease of the artery supplying that
      area of the brain. Severe carotid stenosis is neither sufficient nor necessary to
      produce borderzone infarction. However, it has to be emphasized that patients
      with carotid occlusion are not included in this study.

PMID- 9007747
TI  - The correlation of motor neuron disease with radiation: an objection to the
      hypothesis of Neilson et al.

PMID- 9007746
TI  - Cerebrovascular involvement in the acute phase of bacterial meningitis.
AB  - Cerebral ischaemia is a common complication of bacterial meningitis. Although
      cerebrovascular involvement in the acute phase of inflammation may be
      particularly important for the still unacceptably high morbidity and mortality,
      only, a few studies have investigated cerebrovascular changes in bacterial
      meningitis. We prospectively investigated changes of intracranial cerebral blood
      flow velocities (CBFV) in 22 patients (12 men, 10 women, mean age 48 years, 19
      years, SD) with bacterial meningitis, by means of transcranial Doppler sonography
      (TCD). According to previously published criteria the degree of arterial
      narrowing was assessed and related to the patients' outcome. Elevated CBFVs in
      the middle cerebral artery were documented in 18/22 patients with markedly
      increased systolic peak velocities (CBFV of > 210 cm/s) in 7 patients. Serial
      examinations performed in 11 patients showed elevated CBFV as early as day 1,
      reaching peak CBFV between day 3 and day 6 after onset of symptoms in most cases.
      Furthermore, cerebrovascular involvement was also documented by disturbances of
      physiological slow spontaneous oscillations of blood flow velocities in 5/10
      patients examined with TCD. Low Glasgow Coma Scales (< 7) on admission (29% vs
      0%), focal cerebral ischaemic deficits (29% vs 7%) and, seizures (43% vs 7%) were
      more frequent in patients with CBFV of > 210 cm/s. Finally, a poor clinical
      outcome was significantly related to severe vascular involvement (P < 0.05). In
      conclusion, cerebrovascular complications are frequently found in patients with
      bacterial meningitis. TCD is an easily applicable technique for revealing
      vascular changes non-invasively, even in severely ill patients. Since our data
      suggest an unfavourable course of the disease in association with increased CBFV
      in intracranial arteries, probably indicating vasospasm, TCD could potentially be
      used to identify high-risk patients who could benefit from adjuvant therapeutic
      interventions.

PMID- 9007748
TI  - Neurological manifestations following treatment of Langerhans cell histiocytosis.

PMID- 9007749
TI  - A comparison of two neurologic scoring instruments for multiple sclerosis.

PMID- 9007750
TI  - Voltage-sensitive dye recording using retrogradely transported dye in the chicken
      spinal cord: staining and signal characteristics.
AB  - We describe a novel method for retrogradely labeling specific neuronal
      populations using voltage-sensitive dyes. Styryl dyes were injected into the
      ventral roots of the isolated embryonic chick spinal cord. After waiting several
      hours, the dye labeled motoneurons and autonomic preganglionic neurons. Neuronal
      cell bodies, dendrites and axons were labeled; we presume that the dye traveled
      either by retrograde transport or by diffusion within the membrane of the axon to
      which the dyes were initially applied. Using either a photodiode array or a
      photomultiplier, fluorescence changes could be recorded from motoneurons
      following antidromic or synaptic activation. Several characteristics of the
      fluorescence changes were measured indicating that the signals did indeed reflect
      changes in the motoneuron membrane potential. The best labeling and optical
      signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ and di-12
      ANEPEQ. In the great majority of cases these dyes responded with an increase in
      fluorescence of 1-3% (delta F/F) in response to synaptic or antidromic
      depolarization of the motoneurons. We anticipate that these techniques should be
      useful in the mapping of activity patterns and connectivity in neural networks
      within a defined population of neurons.

PMID- 9007751
TI  - Dye screening and signal-to-noise ratio for retrogradely transported voltage
      sensitive dyes.
AB  - Using a novel method for retrogradely labeling specific neuronal populations, we
      tested different styryl dyes in attempt to find dyes whose staining would be
      specific, rapid, and lead to large activity dependent signals. The dyes were
      injected into the ventral roots of the isolated chick spinal cord from embryos at
      days E9-E12. The voltage-sensitive dye signals were recorded from synaptically
      activated motoneurons using a 464 element photodiode array. The best labeling and
      optical signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ
      and di-12-ANEPEQ. Over the 24 h period we examined, these dyes bound specifically
      to the cells with axons in the ventral roots. The dyes responded with an increase
      in fluorescence of 1-3% (delta F/F) in response to synaptic depolarization of the
      motoneurons. The signal-to-noise ratio obtained in a single trial from a detector
      that received light from a 14 x 14 microns2 area of the motoneuron population was
      about 10:1. Nonetheless, signals on neighboring diodes were similar, suggesting
      that we were not detecting the activity of individual neurons. Retrograde
      labeling and optical recording with voltage-sensitive dyes provides a means for
      monitoring the activity of identified neurons in situations where microelectrode
      recordings are not feasible.

PMID- 9007752
TI  - Analysis of neuro-behavioral Discovery data on the Macintosh computer.
AB  - This paper describes a suite of routines using IgorPro, a powerful analysis and
      graphing software package for the Macintosh computer, to enhance the ability to
      analyze, manipulate, and display data recorded with the Discovery acquisition
      software marketed by DataWave Technologies. The routines are able to time-align
      fast and slow data channels, and are especially useful for analyses that involve
      both neural and behavioral data. The software was designed for eyeblink
      conditioning and vocalization experiments, but it can easily be used for
      analyzing other types of neurobehavioral data. The data are first prepared on the
      PC with routines that inspect the header of the data file and translate the data
      file into a compact binary format that can be read by IgorPro. An option is also
      available to splice out data from unnecessary portions of an intertrial interval.
      The new file is then put on the Macintosh computer for display and analysis by
      IgorPro. These routines enable both neural and behavioral data to be quickly and
      easily reduced, manipulated, and statistically and graphically summarized.

PMID- 9007753
TI  - Measure and statistical test for cross-correlation between paired neuronal spike
      trains with small sample size.
AB  - Recent development of multi-unit recording techniques such as optical recording
      and multi-electrode arrays makes it possible to record neuronal activities from
      tens or hundreds of neurons simultaneously. To analyze functional connections
      between these neurons, cross-correlation analysis has been most commonly applied
      to the hundreds to thousands of pairs of these neurons. However, conventional
      cross-correlation data needs statistical tests for significance especially when
      the sample size of recorded spike trains is small. Here, a multiple
      hypergeometric model based on a transformation of the cross-correlogram data to a
      2 x J table has been suggested. The exact p value for significance can be
      obtained by the generalized Fisher's method with small sample size and a cross
      correlation coefficient for the strength of cross-correlation can be obtained
      based on the R-square analogue for nominal data. For large sample size, chi 2
      test can be applied based on the same transformation. Examples of real spike
      train data set and simulation show that the methods are applicable to the data of
      multi-unit activity with only tens of spikes. These methods are especially useful
      when thousands of cross-correlograms need to be screened quickly and
      automatically.

PMID- 9007754
TI  - In vivo monitoring of extracellular noradrenaline and glutamate from rat brain
      cortex with 2-min microdialysis sampling using capillary electrophoresis with
      laser-induced fluorescence detection.
AB  - The measurement of neurotransmitters by capillary electrophoresis (CE) has
      emerged as a reliable and sensitive method for microdialysis sample analysis.
      This paper describes a method which employs laser-induced fluorescence detection
      (LIFD) of catecholamines and excitatory amino acid derivatives formed after
      reaction with naphthalene-2,3-dicarboxaldehyde. On-line derivatization of very
      small volumes of microdialysis samples (500 nl) is developed before two off-line
      analyses (total run time of less than 10 min) are performed to detect derivatives
      of catecholamines and excitatory amino acids formed in each sample. High
      microdialysis temporal resolution is reached (2-min fractions) for the
      simultaneous monitoring of noradrenaline (NA) and glutamate concentrations from
      rat brain cortex microdialysates. The system performance is evaluated and
      pharmacological characterization of the determination of NA in cortical
      dialysates by CE-LIFD is reported.

PMID- 9007755
TI  - Nerve grafting from spinal cord to spinal nerve: a microsurgical technique in
      cats.
AB  - A ventral surgical approach is described for the grafting of autologous saphenous
      nerves between the spinal cord and the avulsed C7 ventral root in the cat. To
      overcome serious blood loss from the epidural venous plexus, the cats were
      hyperventilated (end tidal PCO2 to about 23 mmHg) and controlled hypotension was
      induced (mean arterial pressure to about 60 mmHg). After selective avulsion of
      the ventral rootlets C7 the saphenous grafts were implanted into the spinal cord
      and coaptated to the avulsed spinal nerve. The combination of advanced anesthetic
      methods and microsurgical techniques appeared to be mandatory to achieve a low
      surgical mortality. Regenerated axons were retrogradely traced using retrograde
      horseradish peroxidase (HRP), and their functional recovery was evaluated by
      means of electrophysiological methods.

PMID- 9007756
TI  - A simple computer based system to analyze Morris water maze trials on-line.
AB  - The development of a system for the acquisition, analysis and storage of data
      from open-field water-maze procedures in which rats learn to escape from water
      onto a hidden platform is described. The use of an object-oriented programming
      language simplifies the programming of the application and provides scientists
      without formal training in computer programming the ability to create their own
      software application. The core hardware is an IBM-compatible AT 486 computer and
      a video capture board. The Microsoft Windows compatible software is written in G
      (LabVIEW) and presents the user a graphically based 'virtual instrument' thus
      simulating functions of real instruments which can be interactively accessed. The
      graphical approach allows the programmer to make fast and simple adaptations of
      the software to suit the specific experimental problem. Image analysis software
      tools (Concept V.i) were integrated into this system which has been used
      successfully for over 2 years in our lab.

PMID- 9007757
TI  - Application of non-linear filters based on the median filter to experimental and
      simulated multiunit neural recordings.
AB  - Two non-linear, high-pass filters based on the median filter are proposed and
      tested as substitutes for linear filtering in applications involving multiunit
      neural recordings. The first, the median-based high-pass (MH) filter, operates by
      subtracting the output from the input of the median filter; it is aimed at
      preserving the shape of the impulses. The second, the negative median-based high
      pass (NMH) filter, sets at zero the positive values in the output of the MH
      filter; it is aimed at transforming the impulses into monophasic waves placed on
      a flat baseline. When applied to experimental recordings and to a template action
      potential, the two median-based filters clearly outperformed two corresponding
      procedures based on a linear filter (moving-average filter). They did not produce
      appreciable distortions of the impulses, whereas their two counterparts induced
      or enlarged lateral lobes, as is the rule for linear high-pass filters. The
      recording display was much improved and impulse identification was made easier.
      When the two filters were applied to simulated recordings and the mean output was
      estimated by averaging and cross-correlation, a certain degree of performance
      deterioration was assessed in conditions of sustained activity and/or noise, with
      a resulting growing similarity to the mean output of the two corresponding,
      moving-average-based filters.

PMID- 9007758
TI  - Effect of brain microdialysis on aminergic transmitter levels in repeated
      cerebral global transient ischemia in rat.
AB  - The effect of repeated transient global ischemia and microdialysis on changes in
      aminergic neurotransmitter release was investigated using the rat four-vessel
      occlusion model of global ischemia. To examine the possible transient or
      permanent changes in neurotransmitter release, ischemia was induced at varying
      time points in 5 groups of rats. The first ischemia occurred either 24 h (groups
      I, II, IV, V) or 96 h (group III) following vertebral artery electro-coagulation
      and guide probe implantation(s), and the second ischemia was induced either 48 h
      (groups I, IV, V) or 72 h (group II) following the first ischemia. To assess the
      consequence of repeated microdialysis on the results, one group of rats (group
      IV) was not dialysed during the first ischemia and another group (group V) was
      bilaterally dialysed during the second ischemia. Finally, amphetamine-induced
      neurotransmitter release was also studied in rats submitted to ischemia and
      compared with that in normal rats. In each case, dopamine, serotonin and their
      main metabolites were measured by HPLC with electrochemical detection. Monoamine
      release was inhibited during the second episode of transient ischemia; this non
      release was linked to the repeated microdialysis and not to the repeated
      ischemia. Although the results of chronic studies using brain microdialysis have
      been widely recognized as valid, the findings presented here indicate that
      combined with ischemia, probe reinsertion modifies the level of neurotransmitter
      release.

PMID- 9007759
TI  - Assessment of neuronal viability with Alamar blue in cortical and granule cell
      cultures.
AB  - Alamar blue, a redox indicator of cell viability in nonneuronal systems, was used
      to assess neuronal viability in cultures prepared from embryonic rat cerebral
      cortex and neonatal rat cerebellum. Alamar blue fluorescence varied linearly with
      cell number and was decreased by treating cortical or cerebellar granule cell
      cultures with excitatory amino acids, exposing cortical cultures to hypoxia and
      glucose deprivation, or inducing apoptotic death in granule cell cultures by
      growth in medium containing a low concentration of K+. Alamar blue fluorescence
      may complement existing methods for measuring neuronal viability and cytotoxicity
      in culture and thereby contribute to the study of cellular mechanisms of
      neurologic disease.

PMID- 9007760
TI  - Aspects of the quantitative analysis of neurons in the cerebral cortex.
AB  - We address three problems concerning the quantitative analysis of nerve cell
      distribution in the cerebral cortex: (i) preparatory tissue deformation
      (shrinkage); (ii) difficulties in differentiating between small neurons and
      astroglia; and (iii) the bias introduced by the counting method. We found that
      staining with Richardson's solution led to no shrinkage in Vibratome-cut sections
      of aldehyde-fixed rat brains, but did result in staining of the neurons and left
      the glial cells unstained. This was in striking contrast to Nissl staining which
      introduced a linear shrinkage of 20-30% and stained all kinds of cortical cells
      indiscriminately. A computer-based unbiased counting method was implemented by
      taking advantage of the stereological procedure referred to as the 'optical
      disector' (Gundersen, H.J.G. (1986) Stereology of arbitrary particles, J.
      Microsc., 143: 3-45).

PMID- 9007761
TI  - Using digital video techniques to identify correlations between behavior and the
      activity of single neurons.
AB  - Digital movies were made of freely behaving rats in a cylinder. At the same time,
      action potentials were recorded from single hippocampal neurons. We describe a
      data processing scheme that allows the spike data and the movie to be merged. A
      display of the ongoing unit activity was added to each frame in the movie. This
      provided a powerful new way to examine the relationships between behavior and
      spike discharge. A second type of data processing, activity-edited video
      identified and used interesting episodes of neuronal activity (e.g. fast firing)
      to select the corresponding frames from the original movie. The activity-edited
      movie can then be viewed to look for behavioral invariances during the episodes
      that were selected according to the cell's firing rate. The feasibility of these
      methods was tested by applying them to post-subicular head direction cells and
      hippocampal place cells because these cell classes have well characterized
      behavioral correlates. The digital video techniques captured the head direction
      and place cell phenomena and provided a novel and robust description of the
      relationship between the firing of these cells and the overall behavior of the
      rat.

PMID- 9007762
TI  - Education and self-management of interferon beta-1b therapy for multiple
      sclerosis.
AB  - A teaching program (Betaseron Instruction) for patients beginning interferon beta
      1b therapy was developed at St. John's Mercy Medical Center in St. Louis,
      Missouri according to Bandura's theory of self-efficacy. Then, a study was
      conducted to determine attitudes of patients with multiple sclerosis (MS) about
      interferon beta-1b (Betaseron) therapy and evaluate the effectiveness of the
      teaching program. In that program, teaching skills mastery and the use of
      modeling and persuasion were used in curriculum development. A survey
      questionnaire in which information about the patients' evaluation of interferon
      beta-1b therapy effects was mailed to 60 patients who had participated in the
      teaching program between December, 1993 and October 1994. Thirty surveys were
      completed and returned. The mean age of participants was 42 years; 22% were men
      and 78% were women. The mean duration of therapy for the study participants was
      10.5 weeks. Qualitative content analysis and tabulation of the one scaled
      question from the 30 completed surveys were performed to obtain outcome
      measurements of cognitive goals and determine the level of self-management of
      therapy. Responses regarding feelings about therapy, the benefits of the teaching
      program, confidence in performing skills that resulted from the use of interferon
      beta-1b therapy, adverse effects produced by the medication and quality of life
      issues were evaluated. The effectiveness of the Betaseron Instruction program and
      the importance of access to support systems from peers and healthcare
      professionals were validated by patient responses. The role of the nurse in
      patient teaching and the provision of support were indicated to be essential to a
      positive outcome in all of the patient surveys submitted.

PMID- 9007763
TI  - Clinical advocacy for persons with epilepsy and mental retardation living in
      community-based programs.
AB  - There is a trend toward reducing the amount of antiepileptic drugs (AEDs)
      prescribed to persons with developmental disabilities and epilepsy who live in
      institutional settings. This trend is much less clear with persons who live in
      community-based settings. A significant percent (58%) of the author's past and
      current clinical caseload of community-based residents benefitted from AED
      reductions. An overview of AED usage of all individuals with mental retardation
      and epilepsy living in homes managed by one community-based vendor was conducted.
      With 52.5% of the residents taking AED polypharmacy, the assessment illustrates
      the need to provide clinical advocacy. The improvement in the quality of life is
      significant for many as evidenced by the three case studies provided. The
      benefits of clinical advocacy and improved health-related quality of life are
      discussed.

PMID- 9007764
TI  - Are alternative long-term-care programs needed for adults with chronic
      progressive disability?
AB  - Long-term care planning for middle-aged adults with progressive neurological
      impairment is a largely unexplored area. The purpose of this study was to examine
      factors that place individuals with progressive disability at risk for
      institutional placement and identify whether innovative long-term care
      preferences would be used if available. The sample of 102 clients with a
      diagnosis of multiple sclerosis (N = 92) or other progressive illnesses (N = 10)
      was mostly female, married and Caucasian, with an average age of 48 years. The
      social support network of family and friends was small; most tangible aid was
      provided by family members. Seventy percent of the participants used community
      services, the most common being a home-health aide (44%) and professional nursing
      services (21%). Medicaid insurance, severity of functional disability and lack of
      social support were associated with greater use of community services.
      Participants could foresee using long-term care alternatives such as a community
      residence (65%), adult day healthcare (63%) and family respite (46%), although
      these services were regarded with some ambivalence. With their knowledge of
      community resources, nurses are in a key position to make early assessments of
      clients' present and future care needs and to suggest needed modifications in
      living arrangements to avoid premature institutionalization.

PMID- 9007765
TI  - Hyperventilation and head injury: controversies and concerns.
AB  - The use of hyperventilation for the treatment of severe head injuries has been
      the standard of care for more than two decades in the prehospital, emergency
      department and critical care settings. Controversy has surrounded its use, even
      when advocates recommended use for all unconscious, head-injured patients.
      Autoregulation, cerebral acidosis control, reduction of elevated intracranial
      pressure and the "steal phenomenon" were thought to be beneficial effects of
      hyperventilation therapy. Current researchers and developments in technology,
      however, have provided controversial information which suggests that
      hyperventilation therapy can be harmful, warranting the need for careful
      monitoring and selective treatment. This information calls into question the use
      of unmonitored hyperventilation therapy in the prehospital and early hospital
      settings.

PMID- 9007766
TI  - Staff action: the nurse researcher in the clinical setting.

PMID- 9007767
TI  - Segond fracture: lateral capsular ligament avulsion.
AB  - Recently, there has been an emphasis placed on incorporating fundamental
      radiology in graduate level physical therapy curricula; however, the majority of
      practicing physical therapists never received formal radiology instruction. As
      health care changes, so must the role of the physical therapist. In a managed
      care environment, it is essential that physical therapists recognize basic
      radiographic findings and understand their clinical ramifications. The purpose of
      this article is to review the literature and provide commentary on avulsion
      fractures of the lateral tibial condyle, known as Segond fractures. Segond
      fractures typically occur by forced internal tibial rotation with the knee
      flexed. This mechanism placed tremendous force on the middle portion of the
      lateral capsule and associated meniscotibial ligament and results in a small bony
      avulsion. The Segond fracture is an important radiographic sign that is critical
      to recognize because it is generally associated with anterior cruciate ligament
      disruption.

PMID- 9007769
TI  - Oxygen consumption, heart rate, and rating of perceived exertion in young adult
      women during backward walking at different speeds.
AB  - Backward walking has gained popularity as an adjunct to treatment for patients
      undergoing rehabilitation for patellofemoral pain syndrome and anterior cruciate
      ligament injuries. Researchers have suggested that backward walking decreases the
      compressive forces at the patellofemoral joint while also preventing
      overstretching of the anterior cruciate ligament. Prior to this study, precise
      prescription of backward walking speeds for women was not possible. The purpose
      of this study was to determine the relationship between heart rate, oxygen
      consumption, and backward walking speeds. Twenty-five healthy, adult female
      volunteers participated in this study. Subjects were tested at speeds of 0.96,
      1.20, 1.43, 1.67, and 1.91 m/sec. Subjects also performed a graded exercise
      stress test. Analysis revealed curvilinear relationships between oxygen
      consumption and speed as well as between heart rate and speed. With these
      results, clinicians may now prescribe specific speeds of backward walking for
      women to elicit a desired cardiopulmonary response.

PMID- 9007768
TI  - Manual massage and recovery of muscle function following exercise: a literature
      review.
AB  - There is currently little scientific evidence that manual massage has any
      significant impact on the short- or long-term recovery of muscle function
      following exercise or on the physiological factors associated with the recovery
      process. In addition, delayed onset muscle soreness may not be affected by
      massage. Light exercise of the affected muscles is probably more effective than
      massage in improving muscle blood flow (thereby possibly enhancing healing) and
      temporarily reducing delayed onset muscle soreness. This paper reviews current
      scientific evidence on the use of manual massage to affect: 1) muscle damage
      caused by eccentric muscle action; 2) retention and recovery of muscle strength
      and performance following "eccentric-mechanical" muscle damage; 3) reduction of
      delayed onset muscle soreness following "eccentric-mechanical" muscle damage; and
      4) recovery of muscle strength and performance following anaerobic exercise.
      Because manual massage does not appear to have a demonstrated effect on the
      above, its use in athletic settings for these purposes should be questioned.

PMID- 9007771
TI  - Test-retest reliability of the lateral step-up test in young adult healthy
      subjects.
AB  - The lateral step-up test is often utilized by clinicians to assess lower
      extremity performance capabilities. Reliability of the lateral step-up test,
      however, is not available. Therefore, the purpose of this study was to determine
      the test-retest reliability of a 15-sec and a 50-repetition lateral step-up test
      on a .15-m (6-inch) and .2-m (8-inch) step. For each of the 15-sec lateral step
      up tests, subjects were asked to perform as many repetitions as possible during
      the 15-sec time frame, while for each of the 50-repetition lateral step-up tests,
      subjects were asked to perform 50 repetitions as quickly as possible. Eighteen
      healthy subjects were studied. Data were analyzed through a repeated measures
      analysis of variance, intraclass correlation coefficients (ICC) (2, 1), and
      standard errors of measurement. The ICC values were .90 and .94 for the .15-m and
      .2-m 15-sec lateral step-up tests and .91 and .96 for the .15-m and .2-m 50
      repetition lateral step-up tests, respectively, revealing test-retest reliability
      to be high for each of the tests. Significant differences, however, were noted
      between the testing days for each of the 50-repetition lateral step-up tests,
      indicating that the measures may not be stable. No significant differences were
      seen between testing days for either of the 15-sec lateral step-up tests. While
      the results support the use of each of the 15-sec lateral step-up tests as
      reliable, stable measures of lower extremity performance, caution should be used
      when interpreting the results of either of the 50-repetition lateral step-up
      tests if used as demonstrated in this study.

PMID- 9007770
TI  - The effect of continuous passive motion duration and increment on range of motion
      in total knee arthroplasty patients.
AB  - There is insufficient information on continuous passive motion (CPM) parameters
      in total knee arthroplasty patients for optimal patient outcomes. We compared CPM
      duration and increments on active and passive range of motion (ROM) in patients
      who underwent a unilateral total knee arthroplasty due to degenerative joint
      disease. Forty-five total knee arthroplasty patients were randomly assigned to
      either a control group, a short CPM duration (3-5 hours per day) group with CPM
      ROM increased 5 degrees twice daily, a short CPM duration group with CPM ROM
      increased daily to patient tolerance, a long CPM duration (10-12 hours per day)
      group with CPM ROM increased 5 degrees twice daily, or a long CPM duration group
      with CPM ROM increased daily to patient tolerance. Active and passive flexion and
      extension were measured goniometrically on each postoperative day that the
      patient was treated by physical therapy. No statistically significant differences
      between groups were found for baseline and final postoperative ROM. The CPM
      groups did not maintain the parameters assigned and were combined, revealing an
      enhanced rate of change of flexion. Most patients opted for a CPM duration of
      between 4 and 8 hours per day and the patient-preferred CPM incremental increase
      in ROM was 6-7 degrees/day.

PMID- 9007772
TI  - Reliability of the Lido Linea closed kinetic chain isokinetic dynamometer.
AB  - Due to increasing emphasis on closed kinetic chain exercises in rehabilitation,
      there is a need to objectively quantify their effectiveness. The purpose of this
      study was to determine the test-retest reliability of the peak force and total
      work scores during a concentric isokinetic leg press pattern using the Lido Linea
      closed kinetic chain isokinetic dynamometer. The static calibration of force
      measurements was established by hanging a series of certified weights from a
      lever arm of known length affixed to the system's force measurement shafts. A
      repeated-trials, multiple-day experimental paradigm was utilized to establish the
      static calibration procedure's reliability. No significant difference was found
      between expected and observed force scores (p > .05). Thirty healthy, active
      subjects (22.5 +/- 3.9 years) performed concentric isokinetic leg press exercise
      under maximal voluntary conditions across a velocity spectrum of 25.4, 50.8, and
      76.2 cm/sec (10, 20, and 30 inch/sec) in a test-retest experimental paradigm,
      separated by 24-72 hours. Intraclass correlation coefficient values (ICC 2,1)
      across Day 1 and Day 2 for peak force and total work ranged from 0.87 to 0.94 (p
      < .05). The data indicate that the Lido Linea closed kinetic chain isokinetic
      dynamometer is an appropriate instrument for assessing concentric isokinetic
      performance during a closed kinetic chain leg press pattern.

PMID- 9007773
TI  - A comparison of trunk extensor strength and squat lifting ability.
AB  - Back testing devices are frequently utilized in the clinic to assess function and
      return to work readiness in place of the job task, yet little research on their
      validity has been reported. This study was conducted to determine if correlations
      exist between squat lifting and isoinertial and isometric trunk extensor
      strength, torso length and isoinertial and isometric trunk extensor strength, and
      body weight and isoinertial and isometric trunk extensor strength. Twenty-eight
      subjects participated in two sessions involving B200 testing and 30.5 cm to
      knuckle lifting ability. Regression and correlations were performed. The results
      indicate that body weight and torso length do not demonstrate a relationship with
      trunk extensor strength, and isometric and isoinertial trunk extensor strength
      cannot be used accurately to estimate one's 30.5 cm to knuckle lifting ability.
      In conclusion, other anthropometric measures should be investigated if
      anthropometrics are used to estimate strength, and functional testing should be
      used to evaluate function.

PMID- 9007774
TI  - Strategies to prevent chronic neonatal lung disease.
AB  - The pathogenesis of chronic neonatal lung disease involves the combined
      iatrogenic insults of oxygen toxicity and barotrauma in addition to lung
      inflammation. Newer ventilator strategies using smaller tidal volumes (3-7 mL/kg)
      in order to avoid overdistension, higher positive end-respiratory pressure and
      lower peak inspiratory pressures decrease barotrauma. Earlier reduction of FiO2
      through the use of surfactant, high frequency ventilation and nitric oxide reduce
      oxygen toxicity. Other measures include careful fluid balance, avoidance of
      prolonged paralysis and early steroids to decrease inflammation.

PMID- 9007775
TI  - New developments in the management of violent children and adolescents.
AB  - Paediatricians are often asked to see children and adolescents with behavioural
      disorders which include an element of violence directed at peers, family members
      or teachers. Inevitably this group of children poses a considerable management
      challenge, irrespective of the multiple aetiological contributions to the
      behaviours. This paper renews some of the evidence for a neurophysiological
      contribution to violent behaviour, provides a rationale for pharmacological
      treatment, and outlines a suggested management plan based on extensive clinical
      experience. The results of this regimen have been highly successful. This regimen
      is inexpensive, successful and empowers both patients and family through the
      development of positive interpersonal interactions.

PMID- 9007776
TI  - Prevalence and impact of chronic childhood conditions in Auckland, New Zealand.
AB  - OBJECTIVE: To establish the prevalence of specific chronic conditions of
      childhood in the Auckland area and to quantify resource use by these children.
      METHODOLOGY: Estimates were made from available registry data and published data
      sources of the population of children with selected chronic conditions resident
      in the Auckland Area Health Board area. Resource use data were extracted for
      admissions to Auckland public hospitals and from providers of community based
      technology services. RESULTS: The largest community prevalence groups are those
      with asthma, intellectual handicap, congenital heart disease and epilepsy.
      Children aged 0-14 with chronic conditions accounted for at least 14,340 hospital
      days stay in Auckland in 1992 at an estimated minimum cost of $7.9 million. Over
      200 children are dependent on technological aids at home. CONCLUSIONS: There are
      sparse data on the numbers and needs of children with chronic conditions in the
      population. A non-categorical approach which crosses disease entities may be the
      best method of meeting common needs.

PMID- 9007777
TI  - Chest radiograph abnormalities in very low birthweight survivors of chronic
      neonatal lung disease.
AB  - OBJECTIVE: To determine whether the neonatal chest radiograph (CXR) at 28 days in
      very low birthweight (VLBW) infants who develop chronic neonatal lung disease
      (CNLD) predicts oxygen therapy duration or CXR abnormalities in early childhood.
      Also, to assess the inter-observer reliability of the radiologists scoring the
      CXR. METHODOLOGY: Clinically well survivors of CNLD (n = 46) had neonatal CXR
      scored (mean age 28.5 days) and compared with current CXR (mean age 40 months).
      The CXR were scored independently and 'blindly' by two paediatric radiologists
      using a standardized scoring system (range 0-10). RESULTS: There was no
      correlation between neonatal CXR scores and current CXR scores for either
      radiologist. There was no association between CXR severity scores and duration of
      oxygen therapy for either neonatal or current CXR. Radiologist A scored the
      current CXR significantly more abnormal than radiologist B [medians (range): 3 (1
      6) vs 1 (0-5), P < 0.001] with reasonable correlation (r = 0.593, P < 0.005) but
      worse than chance agreement (kappa = -0.034). The median scores for the neonatal
      CXR were similar [1.5 (0-8) vs 2 (0-8), P = 0.789] and again there was good
      correlation (r = 0.760, P < 0.0005) although poor individual agreement (kappa =
      0.243) between radiologists. CONCLUSIONS: Follow-up CXR abnormalities in VLBW
      infants with CNLD are usually minor and are not predictive of the duration of
      oxygen therapy that will be required nor of the CXR appearance in early
      childhood. Considerable inter-observer variation exists in the interpretation of
      the CXR in CNLD.

PMID- 9007778
TI  - Hypokalaemia following nebulized salbutamol in children with acute attack of
      bronchial asthma.
AB  - OBJECTIVE: To determine whether use of nebulized salbutamol therapy for treatment
      of an acute attack of asthma in children is associated with hypokalaemia and if
      so what is its frequency, severity and effect on recovery. METHODOLOGY: Forty-six
      children, aged 10 months to 12 years (mean 7.9 +/- 1.5 years) with acute attack
      of bronchial asthma, treated initially with three doses of nebulized salbutamol
      0.15-0.3 mg/kg, every 30 min participated in the study. Blood for serum potassium
      was obtained at the beginning and after three doses of nebulized salbutamol
      therapy, before administering other drugs. RESULTS: The mean +/- SD serum
      potassium level decreased marginally from 3.9 +/- 0.5 mEq/L to 3.7 +/- 0.5 mEq/L
      (P < 0.05). A decrease in serum potassium concentration was noted in 26 (56.5%)
      and hypokalaemia (serum potassium < 3.5 mg/L) in 17 (39%) patients. It was more
      frequent in patients who had received oral salbutamol for the preceding 7 days.
      The average time taken for recovery was longer in patients who had hypokalaemia
      than those who had normal serum potassium concentration (8.6 +/- 2.7 h vs 6.5 +/-
      2.7 h; P < 0.005). CONCLUSIONS: Hypokalaemia may occur in about one-third of
      patients treated with three doses of nebulized salbutamol therapy, especially
      those on prior oral salbutamol therapy. The monitoring of serum potassium
      concentration may be warranted in such patients.

PMID- 9007779
TI  - Why do aboriginal newborns weigh less? Determinants of birthweight for gestation.
AB  - OBJECTIVE: To compare birthweight for gestational age of Aboriginal with
      Caucasian infants and investigate the origins of their differences. METHODOLOGY:
      Data pertaining to birthweight, gestational age at delivery and pathological
      factors were abstracted from birth records of 1301 Western Australian singleton
      Aboriginal pregnancies dated before 24 weeks by ultrasound fetometry and compared
      with routinely collected data pertaining to Caucasian births of the same period.
      RESULTS: Median birthweight for gestation was lower in Aboriginal than in
      Caucasian infants for deliveries after 35 weeks of gestation, and that of pure
      descent lower than that of mixed-descent Aboriginal infants at all gestations.
      Pathological factors (e.g. diabetes, urogenital infections, alcoholism and
      leprosy) occurring more commonly in Aboriginal than in Caucasian pregnancies
      accounted for most of the differences in birthweight for gestation between mixed
      descent Aboriginal and Caucasian infants but a discrepancy of almost 180 g
      remained between pure-descent Aboriginal and Caucasian infants. CONCLUSIONS:
      Identified pathological factors contribute but do not entirely explain the lower
      birthweights for gestation observed in Aboriginal infants.

PMID- 9007780
TI  - Bowel habits of healthy Australian children aged 0-2 years.
AB  - OBJECTIVE: To define the bowel habits of healthy Australian children aged up to 2
      years. METHODOLOGY: One hundred and forty children were recruited in six age
      categories with a minimum of 20 children per category. Data on bowel habit was
      recorded by parents daily for 1 week. RESULTS: Stool frequency decreased with
      age. Ninety-five per cent of infants 0-14 days passed more than two stools per
      day compared with 21% at age 13-24 months. Breastfed infants passed more frequent
      and looser stools than children fed infant formula and solids and also showed a
      wider variation in frequency. CONCLUSIONS: Mean stool frequency decreased with
      age as did the variation. This is a combined effect of age and feed type. These
      data can be used as a guide to the bowel habit of healthy Australian children.

PMID- 9007782
TI  - New South Wales population-based birthweight percentile charts.
AB  - OBJECTIVE: To derive newborn percentile charts using NSW population and hospital
      based data. METHODOLOGY: Birthweight data for liveborn singleton infants were
      obtained from the New South Wales Midwives Data Collection (MDC) from 1990 to
      1994 inclusive (n = 422139). Data were also collected from King George V Hospital
      (KGV) for liveborn singleton infants less than 35 weeks of gestation for 1982-89
      inclusive, and for all gestations for 1990-95 inclusive (n = 30610). Birthweight
      percentiles were derived using the MDC data separately for males and females.
      Head circumference (n = 29090) and birth length percentiles (n = 26973) were
      derived from the KGV data. RESULTS: The charts derived from MDC data had
      generally higher percentiles than previously published charts. These represent
      the largest Australian population-based study published to date. CONCLUSIONS:
      Periodic review of newborn growth charts is recommended because of changing
      ethnic and socio-economic factors.

PMID- 9007781
TI  - Effect of phototherapy on thyroid stimulatory hormone and free thyroxine levels.
AB  - OBJECTIVE: To study the effect of phototherapy for neonatal hyperbilirubinaemia
      on thyroid function as neonatal thyroid screening is sometimes performed during
      exposure to phototherapy. METHODOLOGY: Infants with non-haemolytic
      hyperbilirubinaemia were sequentially allocated to fibre-optic phototherapy,
      conventional daylight phototherapy, or a combination of both. Bilirubin
      concentration was monitored 12 hourly by capillary blood sampling; venous blood
      was sampled for thyroid stimulating hormone (TSH) and free thyroxine (fT4)
      determinations, at start of exposure, at 24 h, end of exposure and 1 day later.
      Comparable unexposed infants served as controls. RESULTS: All 123 study infants
      and 25 controls remained well during the study. Bilirubin levels declined during
      phototherapy, being most rapid in the combination group. The TSH and fT4 values
      at start of exposure were 3.86 +/- 0.41 mU/L (mean +/- SEM) and 33.20 +/- 1.16
      pmol/L, respectively, in the fibre-optic group, 3.62 +/- 0.38 mU/L and 37.22 +/-
      1.76 pmol/L in the daylight group, and 4.40 +/- 0.48 mU/L and 29.91 +/- 1.13
      pmol/L in the combined group, compared with 5.77 +/- 0.40 mU/L and 34.46 +/- 1.68
      pmol/L in the control group. The TSH and fT4 values declined with increasing age
      in the phototherapy and control groups with end of exposure values of 2.90 +/-
      0.28 mU/L and 27.71 +/- 0.71 pmol/L, 2.77 +/- 0.31 mU/L and 33.52 +/- 1.22
      pmol/L, and 3.44 +/- 0.30 mU/L and 27.54 +/- 0.88 pmol/L, respectively, compared
      with 4.21 +/- 0.61 mU/L and 27.19 +/- 2.33 pmol/L (at 72 h) in the control group.
      The pattern of TSH and fT4 decline in the exposed and control groups was similar,
      being related to increasing age. CONCLUSIONS: The validity of neonatal thyroid
      screening is not affected by fibre-optic or conventional phototherapy or by both
      combined.

PMID- 9007783
TI  - Measuring health outcome in paediatrics: development of the RAHC measure of
      function.
AB  - OBJECTIVE: To develop a genetic measure of health outcome (the RAHC Measure of
      Function) for paediatric health services. METHODOLOGY: The RAHC Measure of
      Function (MOF) was modified from the Child Global Assessment Scale. The utility
      and reliability of the MOF was then tested by inter-clinician agreement on case
      scenarios, by inter-clinician agreement in outpatients, by parent-clinician
      agreement in outpatients and by responsiveness to change in acute admissions.
      RESULTS: The inter-clinician agreement on MOF ratings for case scenarios was
      moderately good, with an overall kappa of 0.42; P < 0.0001. Clinicians at
      respiratory and child psychiatry clinics nominated the same or adjacent MOF
      category to describe 100% (95% CI: 71.5-100) and 90% (95% CI: 68.3-98.8%) of 11
      and 20 cases assessed, respectively. Parents nominated the same or adjacent MOF
      category as the attending clinician for 89.7% (95% CI: 72.7-97.8) and 82.9% (95%
      CI: 67.9-92.9) of 29 and 41 children in the same two clinics. Twenty-eight
      inpatient children had an MOF assessed on admission and discharge, and the median
      MOF score improved from 50.5 to 79 points (z = 4.53; P < 0.0001). CONCLUSIONS:
      The MOF is easy to use and provides a valuable description of health outcome that
      parents are able to understand. The MOF is moderately reliable, is likely to be
      sufficiently reliable to compare groups of paediatric patients and is responsive
      to change.

PMID- 9007784
TI  - Risk-stratified nosocomial infection surveillance in a neonatal intensive care
      unit: report on 24 months of surveillance.
AB  - OBJECTIVE: To document the nosocomial infection rate in a single neonatal
      intensive care unit (NICU) in terms of patient workload and device utilization.
      METHODOLOGY: Nosocomial infections have been identified and documented by the
      methodology described by the National Nosocomial Infection Surveillance System
      (NNIS), Centres for Disease Control, Atlanta. In addition, antibiotic usage has
      been surveyed in the NICU and standardized measures of patient exposure to
      antibiotics stratified by birthweight and gestational age have been described.
      RESULTS: Overall nosocomial infection rates compared favourably with the
      published NNIS figures at 6.2 infections per 100 admissions or 4.8 per 1000
      patient days. Infection rates were significantly higher in lower birthweight
      groups. Device-related infection rates in each birthweight cohort were also very
      close to published figures and varied less with birthweight group. Antibiotic
      exposure averaged 12% of total admission days, less than previously published
      data. CONCLUSIONS: The NNIS system is applicable to Australian NICU and provides
      an effective tool for monitoring infection episodes.

PMID- 9007785
TI  - The prediction of hospital admission in children with acute asthma.
AB  - OBJECTIVE: To determine whether a single assessment of children at the time of
      presentation to the emergency department would discriminate accurately between
      those requiring admission and those who could be managed at home and to examine
      the appropriateness of these decisions. METHODOLOGY: Fifty-three children were
      assessed using a table recommended by Australian and New Zealand respiratory
      paediatricians, which categorizes children as probably being able to manage at
      home (group 1), may need admission to hospital (group 2) and certainly need
      admission to hospital (group 3) on the basis of oximetry, presence of wheeze and
      pulsus paradoxus. RESULTS: Nine out of 11 children assigned to group 1 were
      managed at home and 15/17 who were predicted to require admission were admitted.
      No individual component of the assessment dominated the decision made. Of the 25
      children allocated to group 2, 18 were admitted. CONCLUSIONS: The method employed
      was highly predictive of outcome for half of the children who presented with
      asthma. However, 25/53 (47%) were assigned by the table to a recommendation for
      further assessment; this limits its usefulness.

PMID- 9007786
TI  - Isolated congenital tricuspid valve dysplasia: a rare condition mimicking
      persistent pulmonary hypertension of the newborn.
AB  - Isolated congenital tricuspid valve dysplasia is a rare and potentially lethal
      congenital heart disease that can be easily confused with persistent pulmonary
      hypertension of the newborn. We describe a neonate with isolated congenital
      tricuspid valve dysplasia who did not respond to mechanical ventilation but
      improved by tolazoline. Clinicians should be aware that the initial fulminant
      course of this condition may be reversed by reducing the pulmonary vascular
      resistance, thereby allowing time for spontaneous recovery.

PMID- 9007787
TI  - Inhaled nitric oxide during emergency neonatal transportation.
AB  - Inhaled nitric oxide is currently being investigated as a selective pulmonary
      vasodilator for neonates with persistent pulmonary hypertension. The use of
      continuous inhaled nitric oxide during emergency transportation of three
      critically III neonates with meconium aspiration and pulmonary hypertension is
      described. The successful application of this technique may allow safer
      transportation of neonates who require high level intensive care including
      ongoing nitric oxide, high frequency ventilation and/or extracorporeal life
      support. Regionally based nitric oxide-equipped retrieval teams may relieve the
      pressure on smaller neonatal intensive care units to provide inhaled nitric oxide
      therapy and allow centralization of nitric oxide resources, thus facilitating
      development of expertise and the completion of meaningful research programs with
      substantial recruitment.

PMID- 9007788
TI  - Transcatheter embolization of coronary artery fistula with controlled release
      coils.
AB  - The treatment for large congenital coronary cameral fistulas has been surgical
      but with advances in interventional catheterization techniques transcatheter
      embolization of these fistulas with coils or detachable balloons is now possible.
      This report describes occlusion of a congenital coronary arteriovenous fistula in
      a 6-year-old girl.

PMID- 9007789
TI  - In 1994 triple antigen vaccine (DTP) was introduced into the vaccination schedule
      for children age 4-5 years.

PMID- 9007790
TI  - Neurological impairment in ELBW infants.

PMID- 9007791
TI  - Acute abdominal pain in children.

PMID- 9007792
TI  - Severe pleuropneumonia without a cough and myocarditis with mixed mycoplasma
      infection.

PMID- 9007793
TI  - Creation of a modified angiography (endovascular) suite for transluminal
      endograft placement and combined interventional-surgical procedures.
AB  - PURPOSE: To describe early experience with an endovascular suite created for
      procedures requiring surgical access, endograft placement, or combined surgical
      and interventional radiologic expertise. MATERIALS AND METHODS: After examining
      the operating room and angiography environments, practice guidelines, state law,
      and regulatory agency requirements, a multidepartmental task force recommended
      reconfiguring an angiography suite to serve as an endovascular suite. Forty
      patients have been treated; 28 underwent vascular endograft placement and 12
      underwent other combined procedures. RESULTS: Procedures included 31 femoral and
      axillary cutdowns; placement of one aortobifemoral graft, two iliofemoral grafts,
      two femoropopliteal grafts, and two femoral-femoral crossover grafts; two
      abdominopelvic exposures for aortic access, and five endarterectomies, including
      one at the carotid bifurcation performed in combination with common carotid stent
      placement. Three of the abdominopelvic procedures were not planned, including two
      emergency conversions. No patient had to be moved to an operating room. There was
      one major infection (2.5%), two minor wound infections (5%), and one wound with
      delayed healing (2.5%). CONCLUSION: Early experience with a combined surgical
      interventional suite has been favorable, but a vigilant approach is warranted.

PMID- 9007794
TI  - Percutaneous transcatheter liver cell transplantation: an emerging modality and
      its clinical implications.

PMID- 9007795
TI  - Percutaneous balloon-assisted aspiration thrombectomy of clotted hemodialysis
      access grafts.
AB  - PURPOSE: To present experience with percutaneous balloon-assisted aspiration
      thrombectomy (BAT) for the treatment of patients with clotted hemodialysis access
      grafts. MATERIALS AND METHODS: BAT was performed with use of 7-F intravascular
      sheaths and a Fogarty balloon catheter. It was tested with an in vitro flow
      circuit model. Twenty consecutive BAT procedures were performed in 15 patients
      with clotted grafts. The balloon catheter was advanced through the sheath to the
      arterial anastomosis. The balloon was inflated and withdrawn while suction was
      applied from the sideport to recover thrombus. The procedure was repeated for the
      venous limb. BAT was used alone in 12 procedures and in combination with
      urokinase in eight procedures. RESULTS: Almost complete thrombectomy was achieved
      in all tubes (in vitro), with very low venous and arterial embolic fractions.
      Technical success (restored graft thrill and almost complete thrombectomy) was
      achieved in 18 cases (90%). Clinical success (patency after 1 week of dialysis)
      was achieved in 17 cases (85%). CONCLUSION: Percutaneous BAT is feasible in
      recently clotted dialysis grafts.

PMID- 9007796
TI  - Treatment of thrombosed dialysis access grafts: randomized trial of surgical
      thrombectomy versus mechanical thrombectomy with the Amplatz device.
AB  - PURPOSE: To report the preliminary results in a trial comparing the Amplatz
      mechanical thrombectomy (MT) device with surgical thrombectomy (ST) to declot
      occluded dialysis access grafts. PATIENTS AND METHODS: Thirty-seven patients were
      randomly assigned by computer to either ST (n = 18) or MT (n = 19). Diagnostic
      fistulograms were obtained at the end of the procedure, and Doppler ultrasound
      was performed at 1-month follow-up. Plasma free hemoglobin levels were measured
      before, immediately after, and 24 hours after the procedure in the MT group.
      Success was defined as initial success with restoration of flow through the
      graft, primary patency at 30 days, and secondary patency at 30 days. RESULTS:
      Technical success with MT was 89%. Primary patency in the MT series was 47% and
      secondary 30-day patency was 68%. Technical success with ST was 83%. Primary
      patency in the ST series was 77% and secondary patency at 30 days was 77%.
      Angioplasty (n = 18) and stent placement (n = 6) were performed in the MT cases.
      Angioplasty was impossible in one patient. Immediately after MT, plasma free
      hemoglobin levels above normal were noted in 63% of the cases, but these levels
      were within normal levels after 24 hours in 88% of the cases. CONCLUSION: Initial
      success of MT in patients with occluded dialysis access grafts is comparable to
      that of ST. No statistically significant differences in primary or secondary
      patencies were seen.

PMID- 9007797
TI  - Admixture of heparin with urokinase to decrease thrombolysis time and urokinase
      dose in polytetrafluoroethylene dialysis graft recanalization.
AB  - PURPOSE: To determine whether the addition of heparin to urokinase during
      dialysis graft thrombolysis can lower urokinase dose and shorten procedure time.
      PATIENTS AND METHODS: Patients who underwent dialysis graft thrombolysis during
      an 18-month period were studied retrospectively. Twenty patients were treated
      with urokinase alone, and 19 patients were treated with urokinase and heparin.
      Thrombolysis was performed in the angiography suite by using a crossed-catheter
      technique. Urokinase was administered directly into the thrombus. In patients
      receiving heparin, 5,000 IU was added directly to the initial urokinase solution.
      RESULTS: In patients who received urokinase alone, an average of 750,000 U of
      urokinase was used, and the average procedure time was 2 hours 42 minutes. When
      heparin was added, an average of 435,000 U of urokinase was used, and the average
      procedure time was 2 hours. CONCLUSION: The addition of heparin to urokinase can
      decrease both urokinase dose and thrombolysis time in the recanalization of
      dialysis grafts.

PMID- 9007798
TI  - Safety of pulmonary angiography in the 1990s.
AB  - PURPOSE: To examine the safety of pulmonary angiography with low-osmolar contrast
      material and modern angiographic techniques and to analyze periprocedural
      complications with respect to potential predictors. PATIENTS AND METHODS: A
      retrospective review was conducted of data from 547 consecutive patients who
      underwent pulmonary angiography. Minor and major complications were analyzed by
      using several clinical parameters. RESULTS: There were five major (0.9%) and 26
      minor complications (4.8%). Eleven of the 26 minor complications were contrast
      induced nephrotoxicity. There were no periprocedural deaths. Patients with
      complications had an increased incidence of coexistent pulmonary morbidities and
      were of a poorer physical status according to the American Society of
      Anesthesiology criteria. Moderate to severe pulmonary hypertension was correlated
      with major complications. Age, volume of contrast material used, and presence of
      pulmonary embolism were not correlated with complications. CONCLUSION: Pulmonary
      angiography is a safe procedure with an acceptable complication rate. These
      findings should be considered in the selection of an imaging method for the
      diagnosis of pulmonary embolism.

PMID- 9007799
TI  - Prospective evaluation of pulmonary artery pressures during pulmonary angiography
      performed with low-osmolar nonionic contrast media.
AB  - PURPOSE: To determine the effects of pulmonary angiography performed with low
      osmolar, nonionic contrast media on pulmonary artery pressures. PATIENTS AND
      METHODS: In a prospective, uncontrolled clinical trial, pulmonary artery
      pressures (systolic, diastolic, mean) of 116 patients referred for pulmonary
      angiography were recorded before and 1 and 5 minutes after injection of contrast
      material. RESULTS: There was a statistically significant rise in systolic,
      diastolic, and mean pulmonary artery pressure at 1 minute (4.6, 3.4, 4.1 mm Hg,
      respectively) and 5 minutes (3.8, 2.7, 3.4 mm Hg, respectively) after the initial
      contrast material injection (P < .05). Increases were smaller with additional
      injections. Systolic pressure changes at 1 and 5 minutes after the first
      injection were linearly dependent on the volume of contrast material injected (P
      < .05). There was no statistically significant difference in the increase in
      pulmonary artery pressure between patients with pulmonary embolus or pulmonary
      arterial hypertension and those without. CONCLUSION: There is a small but
      statistically significant rise in pulmonary artery pressure after injection of
      low-osmolar, nonionic contrast material for pulmonary angiography; it is unlikely
      to be of clinical significance.

PMID- 9007801
TI  - Biliary strictures in hepatic transplantation: treatment with self-expanding Z
      stents.
AB  - PURPOSE: To determine the long-term results of Gianturco-Rosch Z (GRZ) stent
      placement for the treatment of recurrent, benign biliary strictures in liver
      transplant recipients. MATERIALS AND METHODS: During a 5-year period, eight
      orthotopic liver transplant recipients underwent transhepatic placement of GRZ
      stents to treat 12 recurrent biliary strictures (six anastomotic, six
      intrahepatic). Prior treatment of 11 strictures with balloon dilation therapy had
      failed. Patients were followed up for 1-65 months. RESULTS: Stent placement was
      successful in all patients. Stent position remained stable in all but one
      patient. Three patients died (1, 25, and 28 months after stent placement), all
      with patent stents. Four patients required no further biliary intervention. Two
      of the other four patients needed intermittent biliary balloon dilation with
      removal of bile duct debris. The third patient had a stable, nonobstructing
      stenosis in the stent. The fourth passed his stents and needed no further
      intervention. CONCLUSION: GRZ stents are useful in patients who are refractory to
      repetitive balloon dilation of biliary strictures or who are poor surgical
      candidates.

PMID- 9007800
TI  - Iliac artery evaluation with two-dimensional time-of-flight MR angiography:
      update.
AB  - PURPOSE: To determine the accuracy of two-dimensional (2D) time-of-flight (TOF)
      magnetic resonance (MR) angiography, performed with state-of-the-art equipment,
      in the evaluation of the iliac arteries. MATERIALS AND METHODS: The iliac
      arteries of 50 patients undergoing conventional arteriography for evaluation of
      lower-extremity ischemia or abdominal aortic aneurysm were also imaged with axial
      2D TOF MR angiography. Blinded interpretations of conventional arteriograms and
      MR angiograms were compared. MR angiography was performed with a 1.5-T system
      with 2-mm contiguous axial sections, 60 degrees flip angle, 28-msec repetition
      time, and 7.4-msec echo time. RESULTS: Blinded interpretations of 2D TOF MR
      angiograms matched those of conventional arteriograms in 26 of 50 patients (52%).
      For the diagnosis of obstructive iliac artery lesions, sensitivity and
      specificity with MR angiography were 85% and 59%, respectively. Two of three
      saccular iliac artery aneurysms escaped detection with MR angiography.
      CONCLUSION: Iliac artery evaluation with axial 2D TOF MR angiography is not
      sufficiently accurate to warrant its use as a replacement for conventional
      arteriography in patients who lack contraindications to the latter.

PMID- 9007802
TI  - Percutaneous gallstone removal: long-term follow-up.
AB  - PURPOSE: To evaluate gallstone and symptom recurrence rates, long-term
      complications, and life expectancy after percutaneous gallstone removal. PATIENTS
      AND METHODS: Medical records of 87 patients (mean age, 69 years +/- 14 [standard
      deviation]) undergoing percutaneous gallstone removal between 1987 and 1992 were
      reviewed. Physicians and patients (or their families) were contacted for clinical
      follow-up. Thirty-one patients returned for follow-up ultrasound (US). RESULTS:
      The final study group consisted of 65 patients. Mean survival from the time of
      initial gallbladder drainage was 33 months +/- 19. Over a mean clinical follow-up
      period of 33 months, eight of 65 patients (12%) developed recurrent symptoms; six
      of these eight had recurrent gallstones shown at US. Of 30 patients with
      technically adequate US images (mean follow-up, 14 months +/- 12), 12 (40%) had
      recurrent gallstones. Six of these 12 patients had recurrent symptoms. No long
      term complications were identified. CONCLUSION: The risk of gallstone recurrence
      after percutaneous removal is notable, but the symptom recurrence rate is much
      lower. Percutaneous gallstone removal is beneficial for patients at prohibitive
      surgical or general anesthetic risk.

PMID- 9007803
TI  - Treatment of symptomatic congenital hepatic cysts with single-session
      percutaneous drainage and ethanol sclerosis: technique and outcome.
AB  - PURPOSE: To evaluate the safety and efficacy of percutaneous aspiration and
      ethanol sclerotherapy as the sole treatment for symptomatic, nonneoplastic,
      congenital hepatic cysts. PATIENTS AND METHODS: In a prospective study, 59
      symptomatic, congenital hepatic cysts in 25 patients were treated with ultrasound
      guided percutaneous aspiration and ethanol sclerotherapy. Eleven patients had a
      solitary cyst, and 14 patients had polycystic liver disease. Mean follow-up was 4
      years. RESULTS: Fifty-seven (97%) of 59 sclerotherapy procedures were technically
      successful, and there were no recurrences. Eight cysts in six patients
      disappeared totally. The mean diameter of the remaining 49 cysts decreased from 9
      cm to 3 cm. At the last follow-up visit, 14 patients were asymptomatic, four had
      milder epigastric pain than before the treatment, and seven with polycystic liver
      disease had recurrent symptoms due to growth of nontreated cysts. No major
      complications occurred. CONCLUSION: Percutaneous aspiration with ethanol
      sclerotherapy is a safe, effective, and minimally invasive treatment method for
      symptomatic congenital cysts. It is the initial treatment of choice for all
      patients with symptomatic congenital hepatic cysts.

PMID- 9007804
TI  - Treatment of postoperative lymphoceles with percutaneous drainage and alcohol
      sclerotherapy.
AB  - PURPOSE: To assess the efficacy and safety of percutaneous catheter drainage
      combined with alcohol sclerosis in the treatment of postoperative lymphoceles.
      PATIENTS AND METHODS: Thirteen patients with 14 postoperative symptomatic
      lymphoceles were treated. Drainage catheters were inserted under ultrasound (n =
      13) or computed tomographic (n = 1) guidance. Lymphocele sclerosis was performed
      by instilling 10-100 mL of absolute alcohol into the lymphocele cavity and
      aspirating the alcohol after 30 minutes. Sclerosis sessions were carried out one
      to three times per day, usually three times per week. Catheter sinograms were
      obtained and prophylactic antibiotics administered. Imaging was repeated if
      symptoms or signs of recurrence developed. RESULTS: Successful drainage and
      sclerosis were achieved in all 13 patients. One patient with a recurrence was
      successfully treated with repeated drainage and alcohol ablation. No adverse
      effects of alcohol instillation were seen. The mean duration of catheterization
      was 36 days (range, 17-65 days; median, 30 days). CONCLUSION: Percutaneous
      drainage combined with alcohol ablation is a safe and effective treatment of
      postoperative lymphoceles.

PMID- 9007805
TI  - Loculated pneumothoraces in patients with acute respiratory disease treated with
      mechanical ventilation: preliminary observations after image-guided drainage.
AB  - PURPOSE: To report the clinical impact of image-guided percutaneous drainage of
      loculated pneumothoraces in patients with acute respiratory disease treated with
      mechanical ventilation. MATERIALS AND METHODS: Sixteen loculated pneumothoraces
      were seen in nine patients. Twelve of the 16 lesions were considered suitable for
      drainage because of their size and location. They were percutaneously drained by
      means of image-guided placement of catheters that ranged in size from 16 F to 24
      F. Gas exchange was assessed clinically, and follow-up chest radiographs and
      computed tomographic scans were evaluated. RESULTS: Loculated pneumothoraces were
      reduced in all patients. Improvement in the ratio of arterial oxygen pressure to
      fraction of inspired oxygen was identified in eight patients. All patients showed
      an improved arterial oxygen pressure. CONCLUSION: Image-guided catheter placement
      may play a role in the acute management of loculated pneumothorax and adult
      respiratory distress syndrome. This type of therapy may reverse the deterioration
      of gas exchange and reduce the risk of further pulmonary compromise.

PMID- 9007806
TI  - Percutaneous ureteral biopsy with the Simpson atherectomy catheter.

PMID- 9007807
TI  - Transjugular intrahepatic portosystemic shunt: midterm clinical and angiographic
      follow-up.
AB  - PURPOSE: To determine the impact of Child class and indication for transjugular
      intrahepatic portosystemic shunt (TIPS) placement on patient survival and
      reintervention rate. MATERIALS AND METHODS: Metal stents were used to
      successfully create single shunts in 63 patients during a 3-year period.
      Angioplasty and repeated stent placement were used to maintain shunt patency, and
      patients were followed up clinically and angiographically. Statistical analysis
      of survival and patency was performed with Kaplan-Meier product-limit survival
      functions. A Karnofsky performance status score was derived for each follow-up
      encounter. RESULTS: Early and late mortalities varied with Child class and
      procedure indications. Thirty-day mortality was 19% overall (12 of 63 patients)
      and was 33% for Child class C patients (10 of 30 patients). Thirty-day mortality
      was 31% (four of 13 patients) for patients with ascites and 16% (eight of 50
      patients) for those with bleeding. Reintervention was required in 20 of 33
      patients and was not predictable on the basis of Child class. CONCLUSION: Child
      class and indication for procedures are significant predictors of survival but
      not of the need for reintervention. Ninety-day survivors had uniformly good
      performance status.

PMID- 9007808
TI  - Quantification of intrahepatic portosystemic shunting after placement of a
      transjugular intrahepatic portosystemic shunt.
AB  - PURPOSE: To quantify portosystemic shunting and hepatic portal perfusion after
      placement of a transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS
      AND METHODS: Technetium-99m macroaggregated albumin (MAA) was injected directly
      into the portal veins of nine asymptomatic patients 3 months after TIPS
      placement. Portosystemic shunting was quantified by comparing counts in the lungs
      with those in the liver. One cirrhotic patient and one healthy patient who
      received portal MAA injections were used as controls. RESULTS: No portosystemic
      shunting was found in the healthy patient. In the cirrhotic control patient, 77%
      of the injected activity was in the lungs. Patients with portosystemic shunts had
      even more activity in the lungs. Even stenotic shunts diverted greater than 80%
      of portal blood flow systemically. Flow through the TIPS ranged from 84% to 100%
      (average, 93%); these fractions of flow correlated inversely with portosystemic
      pressure gradients. CONCLUSION: Cirrhotic livers may divert much of the portal
      blood systemically before TIPS placement. Afterward, this proportion rises, and
      most portal flow is diverted into the pulmonary circulation.

PMID- 9007809
TI  - Extrahepatic portal venous stenosis: treatment with percutaneous transhepatic
      stent placement.

PMID- 9007810
TI  - Percutaneous treatment of benign portal vein stenosis after liver
      transplantation.

PMID- 9007811
TI  - Shunt occlusion and acute portal, splenic, and mesenteric venous thrombosis
      complicating placement of a transjugular intrahepatic portosystemic shunt.

PMID- 9007813
TI  - Incorporation of the Gunther temporary inferior vena cava filter into the caval
      wall.

PMID- 9007812
TI  - Lower extremity deep venous thrombolysis: a new approach to obtaining access.

PMID- 9007815
TI  - Variant renal pelvis location.

PMID- 9007814
TI  - Transcatheter embolization for retroperitoneal hemorrhage secondary to acquired
      cystic kidney disease.

PMID- 9007816
TI  - Analysis of the human antibody response to outer surface protein C (OspC) of
      Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii.
AB  - The aim of this study was to determine by Western blotting (WB) the prevalence of
      anti-outer surface protein C (OspC) IgM and IgG antibodies in patients with Lyme
      borreliosis according to each of the three genospecies of Borrelia burgdorferi
      sensu lato. Strains of B. burgdorferi sensu stricto (MUL), B. garinii (DK 6), and
      B. afzelii (DK 26) served as antigen, all of which expressed abundant OspC. We
      examined sera from 117 patients with untreated early and late Lyme borreliosis,
      as well as from 100 blood donors and 29 patients with syphilis. WB results were
      compared with the B. burgdorferi flagellum enzyme-linked immunosorbent assay
      (ELISA) data. OspC from B. burgdorferi sensu stricto showed the lowest diagnostic
      sensitivity. OspC from B. garinii and B. afzelii performed almost identically in
      erythema migrans, with an IgM positive rate of 36% versus 34%, whereas OspC from
      B. garinii performed best in neuroborreliosis (60% versus 44%). The anti-OspC IgG
      response was less prominent than the IgM response and was infrequent in the late
      stages of the disease (0-20%). The benefit of combining the evaluation of anti
      OspC responses with all three species was limited. The overall diagnostic
      sensitivity of WB anti-B. garinii OspC evaluation was, in the early stages of the
      disease, comparable to the results obtained using the flagellum ELISA. In
      erythema migrans and neuroborreliosis, the addition of anti-OspC IgM to the
      flagellum ELISA increased the sensitivity by 15% and 10%, respectively. It can,
      therefore, be concluded that OspC from B. garinii is a suitable OspC test
      antigen, and that supplementary use of OspC from other species adds little to the
      overall diagnostic sensitivity. An ELISA based on B. garinii OspC and native
      flagella seems currently the most promising concept for a future antibody test in
      early Lyme borreliosis.

PMID- 9007817
TI  - Superinfection by Listeria monocytogenes of cultured human enterocyte-like cells
      infected with poliovirus or rotavirus.
AB  - A mixed infection with either rotavirus or poliovirus and Listeria monocytogenes
      was analysed in Caco-2 cells, a tumour-derived cell line, highly susceptible to
      these pathogens. The multiplication of these pathogens, whose usual site of entry
      and/or replication is the intestine, was also followed by electron microscopy.
      Results obtained showed an increase of L. monocytogenes internalisation in cells
      infected with rotavirus, whereas the preinfection with poliovirus had only a
      slight interfering effect on bacterial entry. Analysis of L. monocytogenes
      multiplication in virus-infected cells revealed that rotavirus also promoted
      bacterial replication, which poliovirus hampered replication. Concerning the
      effect of Caco-2 cell invasion by L. monocytogenes on viral replication, we
      observed an increase in rotavirus antigen synthesis but no significant effect on
      poliovirus yield under our experimental conditions.

PMID- 9007818
TI  - Follow-up of human papillomavirus (HPV) DNA and local anti-HPV antibodies in
      cytologically normal pregnant women.
AB  - The high level of progesterone during pregnancy may enhance the transcription and
      replication of genital human papillomaviruses (HPV) through the
      glucocorticoid/progesterone response element found in the long control region of
      the viral genome. In this study, cytologically and colposcopically healthy
      pregnant women were subjected to a follow-up examination. Samples from the
      uterine cervix were collected during early pregnancy (n = 39), in the third
      trimester (n = 31), and a few weeks after birth (n = 30). The presence of HPV DNA
      was detected by polymerase chain reaction (PCR), while local secretory anti-viral
      IgA antibodies were demonstrated by enzyme-linked immunosorbent assay using
      synthetic peptide antigens. Follow-up examination by PCR revealed HPV DNA
      persistence in 5 women. In 5 other cases, HPV positivity changed from negative to
      positive during the follow-up. There was 1 case which changed from positive to
      negative and 1 in which the HPV type changed during the study. Altogether, 12 of
      39 women (31%) were shown to harbor HPV DNA at some time during follow-up. HPV
      DNA positivity increased from 18% during early pregnancy to 27% after birth
      (difference not significant). On the other hand, there was a significant rise in
      the level of local antibodies against HPV antigens (E2, E7, and L2) between
      samples collected in early pregnancy and those collected after birth (P <
      0.0001). This may indicate the reactivation of genital HPV infections during late
      pregnancy.

PMID- 9007819
TI  - Borna disease virus RNA in peripheral blood mononuclear cells obtained from
      healthy dairy cattle.
AB  - We examined natural infection of Borna disease virus (BDV) in 74 healthy dairy
      cattle in Japan. The seroprevalence determined using recombinant BDV p24 protein
      was 20.3%. The prevalence of BDV RNA in peripheral blood mononuclear cells
      (PBMCs) determined by polymerase chain reaction for p24 was 10.8%. Cell fraction
      of the PBMCs revealed the presence of BDV RNA in the T cell-enriched fraction.
      Thus, BDV infection is widespread even among healthy cattle.

PMID- 9007821
TI  - Effects on antitumor activity and cytokine production in the thoracic cavity by
      intrapleural administration of Lactobacillus casei in tumor-bearing mice.
AB  - The effects Lactobacillus casei YIT9108 (LC 9018) on antitumor activity and
      cytokine production in Meth A fibrosarcoma (Meth A)-bearing BALB/c mice were
      examined. Intrapleural (i.pl.) administration of LC 9018 was effective in
      prolonging the survival of Meth A-bearing mice, and frequently cured mice of the
      tumor. However, the results also indicated that the effect of LC 9018 was in part
      inhibited in mice treated with anti-CD3 or anti-CD8 antibody, but not affected in
      anti-CD4 antibody-treated mice. In contrast, LC 9018 had little effect on Meth A
      bearing SCID or nude mice. These results demonstrated that CD8+ T cells
      participated in prolonging the survival of Meth A-bearing mice. Moreover, the
      examination of the production of several cytokines revealed that the production
      of interferon-gamma and interleukin-6 was, in particular, augmented in the
      exudated fluid of the thoracic cavity in BALB/c mice injected with LC 9018 i.pl.
      These results suggested that i.pl. administration of LC 9018 induced those
      cytokines which had the potential to activate the thoracic macrophages or
      proliferate the thoracic lymphocytes to the cytotoxic T cells. Taken together,
      these findings demonstrated that the prolonging effects on survival by i.pl.
      administration of LC 9018 depended on CD8+ T cells, and the i.pl. administration
      of LC 9018 into i.pl. Meth A-bearing mice induced several cytokines which
      participated in the subsequent immunoresponses.

PMID- 9007820
TI  - Isolation of a 33-kDa protein antigen from delipidified Mycobacterium
      tuberculosis H37Rv.
AB  - A 33-kDa protein (TB33) was isolated from a delipidated cell sonicate (CS) of
      Mycobacterium tuberculosis H37Rv (grown in Middlebrook 7H9 broth supplemented
      with glucose) using immobilized metal affinity chromatography (IMAC) on a nickel
      nitrilotriacetic acid (Ni-NTA) column. TB33 could not be isolated from the
      culture filtrate (CF) of M. tuberculosis H37Rv using Ni-NTA. TB33 was recognized
      by monoclonal antibodies (mAb) known to react with proteins of M. tuberculosis
      with a molecular mass of 33/34 kDa; namely, mAb F126-5, F67-1 and F126-2. The N
      terminal amino acid sequence of TB33 was found to be Xaa-Xaa-Thr-Pro-Ala-Asp-Val
      Ser/Cys-Asn-Val-Ala-Ile and thus, shows identity with the N-terminal of antigen
      84 of M. tuberculosis except for two mismatches. Antibodies to TB33 could be
      raised in mice by administering four injections of TB33 (40 micrograms total
      protein). Sera from tuberculosis patients reacted with TB33, while those from
      normal healthy individuals did not.

PMID- 9007822
TI  - The influence of HLA B27 and interferon-gamma on the invasion and persistence of
      yersinia in primary human fibroblasts.
AB  - To examine the role of the human HLA class I molecule B27 in the direct
      interaction of yersinia and human cells we performed experimental infections of
      constitutive HLA B27-positive and -negative human fibroblast monolayers with
      Yersinia enterocolitica O.3. The numbers of yersiniae invading HLA B27-positive
      cells were within the range of HLA B27-negative cells. Treatment of fibroblasts
      with interferon-gamma (IFN-gamma) to enhance HLA B27 expression did not alter
      invasion. IFN-gamma reduced titers of live intracellular bacteria, but not
      bacterial antigens, in a dose-dependent manner. Persistent infection with
      yersinia could be maintained for up to 10 weeks with decreasing bacterial titers
      and more slowly decreasing amounts of yersinial antigens in HLA B27-positive and 
      negative cells. Endogenous HLA B27 does not modulate the direct interaction of
      yersiniae with primary human fibroblasts. This is in contrast to infection of HLA
      B27-transfected murine cells. The protective effect of IFN-gamma for yersinia
      infected cells may be important for controlling complications in patients with
      yersiniosis.

PMID- 9007823
TI  - What is the size of the group A streptococcal vir regulon? The Mga regulator
      affects expression of secreted and surface virulence factors.
AB  - The vir regulon of group A streptococci (GAS) organizes the expression of several
      bacterial virulence factors under the control of the Mga regulator. Previously,
      the genes encoding the Mga regulator (mga), M and M-related proteins (emm, mrp,
      enn) and C5a peptidase (scpA) were reported to be clustered on the streptococcal
      genome in a core vir regulon. In the present study, the genomic regions of a
      serotype M49 strain upstream of mga and downstream of scpA were sequenced to
      assess the boundaries of the vir regulon. In the upstream region, an operon was
      identified that may be potentially involved in substrate transport and is
      independent from Mga regulation. In the downstream region, another Mga
      controlled, scpA-cotranscribed gene was detected. This gene termed orfX encoded a
      385-amino acid (aa) potential surface protein of unknown function. No binding of
      serum proteins to a recombinant ORFX was detectable and phagocytosis resistance
      of an orfX mutant remained unchanged. Downstream of orfX, another Mga-independent
      gene determined the 3' end of the core vir regulon. Utilizing the M49 wild type,
      a mga- mutant and comparative Northern blot hybridization, genes encoding the
      capsule synthesis machinery, streptokinase and streptolysin O, as well as
      erythrogenic toxin A and DNase C were found to be Mga independent. In contrast,
      expression of the genes encoding the cysteine protease SpeB, streptococcin A and
      the oligopeptide permease was reduced in the mga- mutant. This indicated that in
      addition to the core vir regulon, Mga directly or indirectly controls a number of
      genes dispersed throughout the GAS genome.

PMID- 9007824
TI  - Subpopulations of T lymphocytes in the peripheral blood and lymph nodes of Indian
      kala-azar patients.
AB  - Distribution of T cells in the peripheral blood and lymph nodes of Indian kala
      azar (KA) patients was studied by using appropriate phenotypic markers for CD2+,
      CD4+ and CD8+ cells. Significant reduction in the CD2+, CD4+ cell numbers as well
      as CD4+/CD8+ cell ratio was noted in the peripheral blood of active KA cases.
      Such alteration in the T cell population appeared to be a manifestation of the
      disease process as it showed a tendency to return close to normalcy several
      months after successful chemotherapy. Histopathological studies of KA patients
      with lymphadenopathy demonstrated gradual destruction of lymph node follicular
      architecture which correlated well with the severity and duration of illness.
      Massive infiltration of CD2+ cells in the cortical region of lymph node was
      evident. The observed preponderance of CD4+ cells over CD8+ ones in these
      infiltrates was in sharp contrast to the distribution pattern of these cells in
      the periphery. Significance of these findings is discussed in relation to the
      current concepts on the immunology of leishmaniasis and related diseases.

PMID- 9007825
TI  - Trypanosoma cruzi is a potent inducer of interleukin-12 production in
      macrophages.
AB  - Cytokines produced after infection with Trypanosoma cruzi have been shown to be
      crucial in the determination of resistance or susceptibility. Interferon-gamma
      (IFN-gamma) is the predominant cytokine produced after infection and has been
      shown to protect susceptible mice from infection. IFN-gamma production by natural
      killer cells and T cells is induced by interleukin-12 (IL-12). Therefore, the aim
      of our study was to analyze the ability of T. cruzi to induce IL-12 production.
      Spleen cells and bone marrow-derived macrophages incubated with T. cruzi
      trypomastigotes induced high amounts of IL-12p40 mRNA as shown by reverse
      transcriptase-polymerase chain reaction. Lipopolysaccharide (LPS) was less
      efficient in inducing IL-12p40-specific mRNA. Furthermore, biologically active IL
      12, detected by the capacity of the supernatant of infected macrophages to induce
      IFN-gamma production in spleen cells, was produced at very high levels. In
      comparison, macrophages stimulated with LPS secreted drastically less IL-12.
      Interestingly, only live, UV- or gamma-irradiated trypanosomes, but not heat
      killed parasites or lysates, were functional in this respect. In a kinetic study,
      in the supernatant obtained from cultures of infected macrophages, IL-12 was
      already detectable at 2 h after infection, peaked at 32 h and declined after 45
      h.

PMID- 9007826
TI  - Biportal neuroendoscopic microsurgical approaches to the subarachnoid cisterns. A
      cadaver study.
AB  - A preclinical cadaver study was performed to develop the technique of biportal
      neuroendoscopic dissection in the subarachnoid space of the basal cisterns and to
      test the feasibility, utility, and safety of this new technique. In 23 fresh post
      mortem adult human cadavers and 2 formalin-fixed adult human head specimen a
      total of 33 biportal endomicrosurgical dissections into and within the basal
      cisterns were carried out. Following suction of cerebrospinal fluid from the
      subarachnoid space 0 degree-, 30 degrees-, and 70 degrees-lens-scopes (Aesculap
      AG, Tuttlingen, Germany) with outer diameters of 4.2 mm and trochars with outer
      diameters of 5 to 6.5 mm were introduced into the surgical field. 6 different
      endoscopic routes to the basal cisterns and a total of 10 different combinations
      of these approaches for biportal endoneurosurgery could be described, but it was
      found that not all of them were useful and safe. The transventricular approach to
      the prepontine cisterns through the foramen of Monro and the floor of the third
      ventricle, biportally combined with a subfrontal or a subtemporal approach,
      turned out to be not safe enough as it was accompanied by traumatization of the
      fornix at the interventricular foramen and of the hypothalamus at the level of
      the tuber cinereum due to relaxation and caudal shift of the brain following
      suction of cerebrospinal fluid to clear the basal cisterns for the subfrontal or
      subtemporal approaches. Useful and safe endomicrosurgical approaches to the basal
      cisterns were: 1st subfrontal, either epidural or intradural, 2nd subtemporal,
      either anterior or posterior, and 3rd frontal interhemispheric. Various biportal
      combinations of these approaches are estimated to be feasible, useful, and safe
      enough to be performed during microsurgical procedures in the operating room. The
      biportal endomicrosurgical strategy allows for effective and safe dissections
      within the subarachnoid spaces of the basal cisterns. The tip of the
      microinstruments as well as the neighboring anatomical structures can be nicely
      controlled at angles of about 60 degrees to 180 degrees depending on the viewing
      angles of the scopes used and depending on the individual shape of the head. A
      variety of microsurgical instruments has been tested. A number of these will have
      to be redesigned for this new technique. Regions suitable for biportal
      neuroendoscopic subarachnoid preparations are the olfactory groove, the
      prechiasmatic cistern, the region of the optic chiasm, the entire suprasellar
      area, parts of the parasellar area, the pre- and perimesencephalic cisterns, and
      the prepontine cistern.

PMID- 9007827
TI  - Interactive image directed neurosurgery: patient registration employing the
      Laitinen stereo-adapter.
AB  - Fiducial markers visible on both imaging scans and the patient are a convenient
      and accurate method to register the patients head in stereotactic space
      preceeding an interactive image directed neurosurgical procedure. We have been
      using the Laitinen non-invasive relocatable stereo-adapter to carry the fidcucial
      markers both during the imaging and patient registration process. Since the
      adapter can be accurately remounted the surgical procedure can take place at any
      time interval after the imaging study. To compare registration accuracy studies
      were performed using a phantom carrying both surface fiducial markers and
      fiducial markers mounted on the stereo adapter. We have found that total system
      accuracy using either surface or adapter mounted markers and an optical tracking
      system is in the range of 3-5 mm and is acceptable for a broad range of
      neurosurgical applications.

PMID- 9007829
TI  - Stereoscopic synthesized brain-surface imaging with MR angiography for
      localization of a peripheral mycotic aneurysm: case report.
AB  - A patient with subacute bacterial endocarditis and a peripheral mycotic aneurysm
      is presented. We used a combined multi-slice surface anatomy scanning (SAS) and
      contrast-enhanced MR angiography image to determine the exact location of the
      small lesion by applying a skin marker on the scalp and visualizing the
      relationship of the marker to the brain surface structures and to the lesion.
      This technique was useful for the removal of a small peripheral aneurysm using
      only a limited craniotomy.

PMID- 9007828
TI  - Stereotactic aspiration and drainage of brain abscesses. Experience with 9 cases.
AB  - The first-line treatment for brain abscesses is still a much-debated argument.
      Recently, stereotactic aspiration of these lesions has gained ground as a valid
      alternative to the traditional medical and/or surgical therapeutical treatments.
      From 1991 to 1995, 9 patients affected by intracranial abscesses were surgically
      treated by stereotactic puncture of the lesion and drainage of pus, using the
      Kelly-Goerss stereotactic system. Multiple abscesses were present in one case.
      Specific antibiotic therapy was used in the post-operative stage, when possible.
      One death occurred four weeks after surgery for acute ischemia of the brain stem.
      Follow-up CT demonstrated gradual resolution of the abscesses in all the cases
      and a successful return to normal daily life in all the surviving patients. In
      one case, recurrence of the abscess occurred two months after resolution: a
      successful result was obtained by steroids and broad-spectrum antibiotic therapy
      alone. Possible advantages of this technique are discussed and compared with the
      traditional routes. The literature concerning this argument is reviewed.

PMID- 9007830
TI  - Microanatomical basis for the third ventriculostomy.
AB  - In the last few years, there has been a resurgence of interest in endoscopic
      third ventriculostomy as a treatment for obstructive hydrocephalus. Although
      various techniques have been used to perform this procedure, not enough emphasis
      has been placed on the microanatomical details of the third ventricle and
      surrounding cisterns in relation to this procedure. Using a surgical microscope
      we examined the microsurgical anatomy of the floor of the third ventricle floor
      and related subarachnoid cisterns in 20 adult brains using the "immersion
      technique" in conjunction with microsurgical dissection. We believe that the
      optimal place to fenestrate is the midline of the floor of the third ventricle,
      behind the infundibular recess and in front of the mammillary bodies,
      communicating the third ventricle with the anterior interpeduncular cistern,
      minimizing the risk for vascular lesions. Stereotactic third ventriculostomy is a
      safe and effective way of re-establishing normal cerebrospinal fluid flow
      dynamics in selected cases of obstructive hydrocephalus. However, in an
      endoscopic exposure only a small portion of the anatomy can be seen at any one
      time, and important neurovascular structures may be located adjacent to the
      endoscope, but outside of the visual range of the lens. A thorough understanding
      of the microanatomy of the neural and vascular structures surrounding the third
      ventricle and related cisterns is essential in order to improve surgical results
      avoiding complications.

PMID- 9007832
TI  - Third ventriculostomy for symptomatic syringomyelia using flexible endoscope:
      case report.
AB  - Using a flexible endoscope, we performed a third ventriculostomy to treat a
      patient with communicating syringomyelia accompanied by enlarged cerebral
      ventricles. Her clinical improvement was rapid and dramatic. Postoperative
      magnetic resonance scan demonstrated shrinkage of the cervical syrinx as well as
      the ventricles. This simple and safe flexible endoscopic third ventriculostomy
      could be a treatment of choice for communicating syringomyelia accompanied by
      enlarged cerebral ventricles.

PMID- 9007831
TI  - Third ventriculostomy: post-operative ventricular size and outcome.
AB  - Reduction in ventricular size after third ventriculostomy often appears minimal.
      In order to determine if changes in ventricular size are a reliable measure of a
      functioning ventriculostomy, and which ventricle is more sensitive to this
      change, we compared pre-operative lateral and third ventricular diameter with
      serial post-operative axial CT and/or MRI scans in a series of 27 consecutive
      third ventriculostomies. Of eleven patients with aqueductal stenosis, fifteen
      with mass lesions and one with a Chiari I, six patients were shunted before 1
      month and two refused radiographic follow-up. In the remaining nineteen patients,
      with an average follow-up of 20 months, the average (s.d.) third ventricular
      change was -30 (11)% for twelve improved patients, and +13 (18)% for the seven
      patients without improvement (p < 0.00001). The average (s.d.) lateral
      ventricular change was -23 (15)% for improved patients, and +5 (21)% for those
      without improvement (p < 0.005). A decrease in third ventricular size by a least
      15% was seen in all significantly improved patients. Similar results were found
      in 9 patients with scans performed exactly one month post-operatively. Among the
      aqueductal stenosis patients, factors associated with failure were age > 70 years
      associated with symptoms of NPH, symptomatic, shunted hydrocephalus since before
      age 1 year and a history of meningitis. In the remaining patients, failures
      occurred with a history of meningitis, subdural hematoma, Chiari I malformation
      or following open tumor surgery or intraventricular AVM rupture. Although both
      the lateral and third ventricles change in diameter after third ventriculostomy,
      the third ventricular diameter is more reliable. As early as one month post
      operatively, ventricular diameter reflects the clinical outcome of the operation.
      A decrease in third ventricular diameter by at least 15% was seen in all
      successful cases and in none of the failures.

PMID- 9007833
TI  - Anomalies and malformations of lumbar spinal nerve roots.
AB  - In spinal surgery, malformations of lumbar nerve roots and their coverings may
      result in difficult or even faulty differential diagnoses and intraoperatively in
      surgical peculiarities and problems. In 5000 operations of the lumbar spine
      carried out within a ten-year period, 35 cases of malformation of the lumbar
      nerve roots were observed with 17 conjoined nerve roots emerging from the dural
      sac and 18 perineurial cysts in the form of cystic anomalies in the transition
      area of dural and arachnoid root sac into the perineurium of the spinal nerve.
      Due to the experience gained from these operations carried out to date,
      radiologic findings as to imaging as well as their interpretation, indications
      for surgery and intraoperative management are being discussed.

PMID- 9007834
TI  - The "rete mirabile" of the clivus and the dorsum sellae. A microanatomical study.
AB  - The osteofibrous space underneath the dura mater of the dorsoclival area was
      studied with respect to the arterial branches arising from the internal carotid
      artery at this level. Special attention was given to the main variations of
      branching and anastomosing patterns found in this area. Our results indicate that
      the meningohypophyseal trunk is the main supplier of the dorsoclival area. The
      dorsal meningeal artery was present in all cases. In the course of this vessel
      three main variations were observed. The inferior hypophyseal and the tentorial
      artery also contributed to the arterial supply of this region. A large number of
      anastomoses between the internal and external carotid artery was present as well.
      Because of the refinement of microsurgical and interventional techniques
      pathological lesions like tumors and vascular malformations of the dorsoclival
      area are frequently accessible. The knowledge of the microvascular anatomy of the
      clivus and the dorsum sellae is important as the rich collateral network found in
      this area may contribute to the arterial supply of pathological lesions arising
      here.

PMID- 9007835
TI  - Signalling properties of lysophosphatidic acid in primary human skin fibroblasts:
      role of pertussis toxin-sensitive GTP-binding proteins.
AB  - We have investigated the signalling properties of the naturally occurring
      intercellular signalling molecule lysophosphatidic acid (LPA) in primary human
      skin fibroblasts. LPA stimulated phospholipase C activity resulting in the
      formation of inositol 1,4,5-trisphosphate (IP3) which was accompanied by a
      concentration-dependent increase in intracellular calcium concentration
      ([Ca2+]i). The increase in [Ca2+]i was subject to homologous desensitisation but
      not to heterologous desensitisation by sphingosine-1-phosphate. The half-maximal
      effect of LPA on the rise in [Ca2+]i was attained at 7-20 nM. IP3 formation and
      Ca2+ mobilisation were highly pertussis toxin (PTX)-sensitive (100% and 75%,
      respectively). LPA also inhibited forskolin-stimulated formation of cAMP, which
      was partially reversed (51%) when fibroblasts were pretreated with PTX. To
      directly test the involvement of guanine nucleotide-binding regulatory proteins
      (G proteins), LPA-induced binding of the stable GTP analogue GTP gamma S was
      measured. LPA induced an increase in GTP gamma S binding, which was completely
      inhibited by PTX, implicating the involvement of Gi-type G proteins in LPA
      signalling. Furthermore, LPA increased DNA synthesis and cell proliferation.
      Finally, LPA induced the migration of human skin fibroblasts, which in
      conjunction with the stimulation of cell growth strengthens the presumed
      involvement of LPA in wound healing and tissue regeneration. Both effects (cell
      growth and migration) were almost completely PTX-sensitive. Overall, these
      investigations in primary cultures of human skin fibroblasts confirm and extend
      our knowledge about LPA signalling, suggesting a pivotal role of receptor coupled
      activation of Gi-type proteins at least in this cell type.

PMID- 9007836
TI  - Regulation of CYP 2 A 5 induction by porphyrinogenic agents in mouse primary
      hepatocytes.
AB  - All cytochrome P450 (CYP) enzymes contain heme as a prosthetic group. In contrast
      to other CYP enzymes, murine CYP 2 A 5 is upregulated in vivo by several agents
      that disturb cellular heme balance. To test the hypothesis that porphyrinogenic
      agents have the common feature of being able to increase CYP 2 A 5 expression,
      mouse liver primary hepatocytes were exposed to various porphyrinogenic chemicals
      and changes in CYP 2 A 5 catalytic activity and levels of mRNA were monitored.
      Phenobarbital increased hepatic CYP 2 A 5-mediated coumarin 7-hydroxylase (COH)
      activity (13.2-fold) and the amount of CYP 2 A 5 steady-state mRNA (10.6-fold).
      Hepatocyte COH activity was increased also by the ferrochelatase inhibitor
      griseofulvin and the protoporphyrinogen oxidase inhibitor acifluorfen (about 9
      fold induction). Of these inducers, only phenobarbital affected CYP 1 A 12 and
      CYP 2 B 10 expression. In contrast, many other porphyrinogenic agents such as
      cobalt, 2,2,4-trimethyl-1,2-dihydroquinoline (TMDQ), 1-[4-(3-acetyl-2,4,6
      trimethylphenyl)-2,6-cyclohexanedionyl]-O-eth yl propionaldehyde oxime (ATMP),
      aminotriazole, and thioacetamide either decreased or had no effect on CYP 2 A 5.
      The increases in COH activity and CYP 2 A 5 mRNA were unaffected by combined
      treatment with the inducers and heme arginate, suggesting that heme is not a
      regulator of CYP 2 A 5 induction. Treatment with actinomycin D totally abolished
      both constitutive CYP 2 A 5 expression and its inducibility, suggesting that a
      transcriptional component is involved. These data suggest that, in mouse primary
      hepatocytes, CYP 2 A 5 induction is not a universal response to disturbed
      cellular heme biosynthesis.

PMID- 9007837
TI  - Repeated treatment with antidepressant drugs induces subsensitivity to the
      excitatory effect of 5-HT4 receptor activation in the rat hippocampus.
AB  - The effect of repeated treatment with various antidepressant drugs on the
      reactivity of CA1 neurons to the 5-HT4 receptor agonist zacopride was examined.
      Zacopride decreased the calcium-activated afterhyperpolarization and adaptation,
      it also elicited a slow membrane depolarization associated with an increase in
      input resistance. All those effects may have contributed to the zacopride-induced
      increase in the amplitude of population spikes, evoked in the CA1 cell layer by
      stimulation of the Schaffer collateral/commissural pathway. The later effect of
      zacopride was concentration-dependent and was antagonized by the 5-HT4 receptor
      antagonist DAU 62805. Repeated (14 days, twice daily), but not single,
      administration of the antidepressant drugs imipramine, citalopram, fluvoxamine
      and paroxetine (10 mg/kg) attenuated the effect of zacopride on population
      spikes. Because inhibitory 5-HT1A and excitatory 5-HT4 receptors are colocalized
      on pyramidal neurons, and our previous data demonstrated an increase in the 5
      HT1A receptor-mediated inhibition after repeated treatment with antidepressants,
      we conclude that treatment with antidepressant drugs may enhance the inhibitory
      effect of 5-HT directly, by increasing the 5-HT1A receptor responsiveness, and
      indirectly, by inducing subsensitivity to the 5-HT4 receptor activation.

PMID- 9007839
TI  - Threshold of dopamine content and D1 receptor stimulation necessary for the
      expression of rotational behavior induced by D2 receptor stimulation under normo
      and supersensitive conditions.
AB  - We measured the minimum amount of endogenous dopamine (EDA), necessary for the
      expression of rotational behavior induced by D2 receptor stimulation in striatal
      or medial forebrain bundle (MFB) lesioned rats. We correlated these results with
      the minimum dose of D1 receptor agonists needed to substitute EDA in its
      permissive role for D2 motor effects to take place. Rats with unilateral
      quinolinic acid (QA) striatal or 6-hydroxydopamine (6-OHDA) MFB lesions were
      given increasing doses of the tyrosine hydroxylase inhibitor alpha-methyl-para
      tyrosine (AMPT) in combination with a fixed dose of the D2 receptor agonist
      quinpirole (trans-(-)-4aR-4,4a,5,6,7,8,8a,9-Octahydro-5-propyl-1H-pyrazolo(3, 4
      g) quinoline hydrochloride) and tested for rotational behavior. The animals were
      later sacrificed and striata removed; EDA was measured by high performance liquid
      chromatography (HPLC). Rotational responses were abolished by increasing doses of
      AMPT inducing a stepwise depletion of EDA. EDA content and rotational behavior to
      D2 stimulation showed a high degree of correlation. There was an abrupt reduction
      in rotational behavior at dopamine levels of 50-60% of controls in both animal
      models. In addition, striatal or MFB lesioned rats which were maximally depleted
      of dopamine by AMPT pretreatment received a fixed dose of quinpirole and then
      challenged with increasing doses of a D1 receptor agonist SKF 38393 ((+/-)-1
      Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride). Rotational
      behavior was restored by SKF 38393 in both animal models in a dose-dependent
      fashion. Our results confirm the need for simultaneous D1/D2 stimulation in the
      generation of rotational behavior in both animal models. Moreover, they
      demonstrate the existence of a threshold level of D1 stimulation necessary to
      exert its permissive role on D2 mediated responses.

PMID- 9007838
TI  - Effects of long-term treatment with the alpha 2-adrenoceptor antagonist
      mirtazapine on 5-HT neurotransmission.
AB  - Mirtazapine (ORG 3770, Remeron) is a nonselective alpha 2-adrenoceptor antagonist
      with antidepressant activity in major depression. The aim of the present study
      was to assess, using an in vivo electrophysiological paradigm, the effect of long
      term treatment with mirtazapine on pre- and postsynaptic alpha 2-adrenoceptors
      and on 5-HT neurotransmission in male Sprague-Dawley rats. A 21-day treatment
      with mirtazapine (5 mg/kg/day, s.c., using osmotic minipumps) increased the
      spontaneous firing activity of locus coeruleus noradrenaline (NA) neurons. Their
      firing activity was back to normal 48 h after removing the minipump. However,
      this treatment did not modify the dose-response curve of the suppressant effect
      of the alpha 2-adrenoceptor agonist clonidine on the firing activity of NA
      neurons. The spontaneous firing activity of dorsal raphe 5-HT neurons was also
      markedly increased in mirtazapine-treated rats, and was back to normal 48 h after
      removing of the minipump. The dose-response curve of the suppressant effect of
      clonidine on the firing activity of 5-HT neurons was altered in mirtazapine
      treated rats. Furthermore, it was further shifted to the left after a 48-h
      washout. Long-term mirtazapine treatment did not modify the suppressant effects
      of microiontophoretically-applied NA and 5-HT on the firing activity of CA3
      dorsal hippocampus pyramidal neurons. However, this mirtazapine treatment
      antagonized both the enhancing effect of a low dose (10 micrograms/kg, i.v.) and
      the reducing effect of a high dose (100 micrograms/kg, i.v.) of the alpha 2
      adrenoceptor agonist clonidine on the effectiveness of the electrical stimulation
      of the ascending 5-HT pathway in suppressing the firing activity of dorsal
      hippocampus CA3 pyramidal neurons. After a 48-h washout, only the effect of the
      high dose of clonidine was attenuated, suggesting a desensitization of the
      terminal alpha 2-adrenergic heteroreceptor, but not of the terminal alpha 2
      adrenergic autoreceptor. The decrease in the effectiveness of the stimulation
      upon increasing its frequency from 1 to 5 Hz (due to the activation of terminal 5
      HT autoreceptors) was unaltered after the long-term mirtazapine treatment. In
      conclusion, the tonic activation of postsynaptic 5-HT receptor is enhanced by a
      21-day treatment with mirtazapine, as a result of a sustained increase in 5-HT
      neuron firing activity in the presence of decreased function of alpha 2
      adrenergic heteroreceptors located on 5-HT terminals in the dorsal hippocampus.

PMID- 9007840
TI  - Effect of probenecid on depolarizations evoked by N-methyl-D-aspartate (NMDA) in
      the rat striatum.
AB  - Kynurenic acid is an endogenous, competitive antagonist of the N-methyl-D
      aspartate (NMDA) receptor glycine site. Accordingly, increasing the brain
      extracellular concentration of this metabolite may be a suitable alternative to
      administration of exogenous NMDA antagonists for the treatment of neurological
      disorders involving excessive NMDA-receptor activation. As competitive inhibition
      of organic anion transport by probenecid increased brain extracellular levels of
      kynurenic acid, the purpose of this study was to examine whether intracerebral
      application of probenecid reduced depolarizations evoked at the same tissue site
      by NMDA. Microdialysis probes incorporating an electrode were implanted into the
      striatum of rats and perfused with artificial cerebrospinal fluid. Local
      depolarizations were produced by perfusing 200 microM NMDA for 2 min, either
      alone, or co-applied with 1, 5 or 20 mM probenecid. The lowest concentration of
      probenecid had no effect. At 5 mM, probenecid abolished the hyperpolarization
      which consistently followed NMDA-responses, but the slight decrease in
      depolarization amplitude did not reach significance. Inhibition of post
      depolarization hyperpolarization suggests that sustained, high extracellular
      concentrations of probenecid reduce the capacity of the tissue to recover from a
      depolarizing stimulus, presumably because intensive transport of probenecid
      imposes a heavy load on Na+, K(+)-ATPase. At 20 mM, probenecid inhibited NMDA
      evoked depolarization by approximately 60% (from 4.7 +/- 0.7 mV to 2.1 +/- 0.2
      mV; n = 6, P < 0.005). This effect was more marked 30 min after returning to
      perfusion with normal artificial cerebrospinal fluid, suggesting that high
      concentrations of probenecid may be toxic to nerve cells, or initiate long
      lasting effects linked to inhibition of the transport of important organic
      anions. These data suggest that inhibition of organic anion transport is not, by
      itself, sufficient to protect against neurological disorders involving excessive
      NMDA-receptor activation. However, results from other studies suggest that it may
      be a valid strategy for enhancing the neuroprotective actions of treatments which
      stimulate kynurenic acid synthesis, or those of exogenous glutamate receptor
      antagonists.

PMID- 9007841
TI  - D-serine modulates the NMDA receptor/nitric oxide/cGMP pathway in the rat
      cerebellum during in vivo microdialysis.
AB  - Several lines of investigation indicate that D-serine may be an endogenous ligand
      for the glycine site of N-methyl-D-aspartate (NMDA) receptors in some CNS
      regions. We here studied the in vivo effects of D-serine on the NMDA
      receptor/nitric oxide/cGMP pathway by monitoring extracellular cGMP in the
      cerebellum of freely-moving rats subjected to transcerebral microdialysis. Local
      application of NMDA (200, 500 microM) through the dialysis probe for 20 min
      evoked transient, concentration-dependent cGMP responses which peaked in the
      fraction of drug administration, the nucleotide levels returning to basal values
      after 40 min. The NMDA-induced elevation of the extracellular nucleotide was
      completely inhibited by the selective receptor channel blocker dizocilpine (MK
      801) locally co-perfused at the concentration of 10 microM. The non-competitive
      antagonist had no effect on its own suggesting that endogenous glutamic acid does
      not tonically activate NMDA receptors. The effect of 200 microM NMDA was largely
      attenuated by 30 microM 7-chloro-kynurenic acid and completely abrogated when the
      concentration of the strychnine-insensitive glycine receptor antagonist was
      raised to 100 microM. D-serine (300 microM), perfused in the presence of 7-chloro
      kynurenate (30 microM), was able to fully restore the NMDA (200 microM)-induced
      increase of cGMP extracellular levels. On the other hand, the D-amino acid
      directly potentiated in a concentration-dependent manner (0.3, 1 and 10 mM) the
      NMDA (200 microM)-evoked cGMP production whereas it was inactive on its own.
      These data show that in vivo the activation of the strychnine-insensitive glycine
      site is essential for the functioning of the NMDA receptor complex and can be
      activated by the selective agonist D-serine. They also confirm that cerebellar
      NMDA receptors do not have their glycine sites saturated.

PMID- 9007842
TI  - Adenosine A2A receptor stimulation increases release of acetylcholine from rat
      hippocampus but not striatum, and does not affect catecholamine release.
AB  - Rat striatal and hippocampal slices, preincubated with [3H] dopamine (DA) ?or
      [3H] noradrenaline (NA)] and [14C] choline, were superfused continuously and
      stimulated electrically. 2-chloroadenosine (2-CADO 0.001-100 microM), a non
      selective adenosine receptor agonist, produced a concentration-dependent
      inhibition of the electrically evoked DA and acetylcholine (ACh) release from the
      striatal slices and of the electrically evoked NA and ACh release from the
      hippocampal slices. 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 3, 30 and 200 nM),
      a selective adenosine A1 receptor antagonist, caused a concentration-dependent,
      parallel, rightward shift of the 2-CADO concentration-response curve, consistent
      with competitive antagonism. The pA2 values ranged between 8.4 and 8.8. In the
      case of ACh release from the hippocampus, but in no other case, was there an
      increase in release of radioactivity at low concentrations of 2-CADO in the
      presence of DPCPX. The stimulation in the hippocampus could be blocked by a
      selective adenosine A2A receptor antagonist KF 17837. By itself KF 17837 (0.1-100
      microM) had no effect on electrically evoked NA release from hippocampal slices,
      but decreased electrically evoked ACh release. This inhibition was counteracted
      by DPCPX (1 microM). These results show that, under the conditions used, DA
      release in the striatum, and NA release in the hippocampus, as well as ACh
      release from the striatum are regulated by adenosine A1 but not by adenosine A2A
      receptors. By contrast, ACh release from the hippocampus is tonically regulated
      both by adenosine A1 receptors, which inhibit release, and by adenosine A2A
      receptors which stimulate release.

PMID- 9007843
TI  - Different molecular forms of cholecystokinin and CCKB receptor binding in the rat
      brain after chronic antidepressant treatment.
AB  - Cholecystokinin (CCK) is a neuropeptide recently implicated in affective
      disorders. This study aimed at measuring the levels of different molecular forms
      of CCK and the binding characteristics of CCKB receptors in the rat brain after
      three weeks of treatment with four different antidepressants, imipramine,
      amitriptyline, desipramine, and citalopram (all at the dose of 10 mg/kg once per
      day i.p.). Chronic treatment with imipramine and desipramine had a significant
      immobility-reducing effect in the Porsolt's swim test. The effect of
      amitriptyline, albeit in the same direction, was not significant, and citalopram
      had no effect in this test. In the elevated plus-maze test of anxiety, all drugs
      tended to increase the number of open arm entries and the ratio open/total arm
      entries, but only the effects of imipramine were statistically significant. None
      of the treatments affected the total levels of CCK or the levels of CCK-8
      sulphated, CCK-8-nonsulphated, CCK-5, or CCK-4 in the frontal cortex. There was
      no effect of the treatments on CCKB receptor binding in the frontal cortex,
      hippocampus, or striatum. Imipramine and amitriptyline, however, increased the
      affinity of CCKB receptor binding in the hypothalamus. Thus, no consistent effect
      of chronic antidepressant treatment on the CCK-ergic neurotransmission in the
      rats was found.

PMID- 9007844
TI  - Binding domains for blockers and substrates on the dopamine transporter in rat
      striatal membranes studied by protection against N-ethylmaleimide-induced
      reduction of [3H]WIN 35,428 binding.
AB  - Binding sites for 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)[3H]tropane ([3H]WIN
      35,428) on rat striatal membranes were alkylated with N-ethylmaleimide (NEM), and
      the protective potency was measured of the blockers cocaine, N[1-(2
      benzo[b]thiophenyl) cyclohexyl]piperidine (BTCP), benztropine, WIN 35,428; and
      nomifensine, and of the substrates dopamine, norepinephrine, S(+)-amphetamine,
      tyramine, and metaraminol. In general, the protective potency was lower (at least
      3 times) than the potency in inhibiting [3H]WIN 35,428 binding with the compounds
      present under the same experimental conditions used for the NEM-induced
      alkylation. However, the disparity was substantially greater for all substrates
      tested (10- to 93-fold) than for the blockers (2- to 6-fold), especially cocaine
      and BTCP (3-fold). [3H]WIN 35,428 binding was best described by a l-site model
      under the present conditions. The results are discussed in terms of models
      involving blocker-induced conformational changes and overlapping nonidentical
      binding domains for blockers and substrates.

PMID- 9007845
TI  - Functional evidence against the existence of beta 2-adrenoceptors mediating
      positive intropic effects in guinea-pig right ventricular myocardium.
AB  - In guinea-pig isolated papillary muscles we studied the positive inotropic
      effects of the beta-adrenoceptor agonists isoprenaline, fenoterol and
      noradrenaline in the presence and absence of the beta 1-selective antagonist
      atenolol and the beta 2-adrenoceptor antagonist ICI 118.551. In Schild regression
      analysis pA2 values, for either atenolol (7.14-7.16) and ICI 118.551 (6.79-6.84)
      were independent of the agonists used. These results support the view that the
      inotropic response in guinea-pig ventricular myocardium is mediated by beta 1
      adrenoceptors only.

PMID- 9007846
TI  - Kinetics and state-dependent effects of verapamil on cardiac L-type calcium
      channels.
AB  - The voltage dependence and the kinetics of block by verapamil of L-type calcium
      current (ICa) were investigated in ventricular myocytes from rat hearts using the
      whole-cell patch-clamp technique. ICa was elicited repetitively in response to
      depolarizing voltage pulses from -80 mV to 0 mV at different pulse intervals and
      durations. Verapamil reduced the magnitude of ICa in a frequency-dependent manner
      without tonic component. The time course of ICa remained unchanged suggesting
      that not open but inactivated channels were affected by the drug. The interaction
      of verapamil with inactivated channels was investigated by the application of
      twin pulses. In the presence of verapamil, the duration of the first pulse
      significantly determined the magnitude of ICa during the second pulse. Variation
      of the duration of the first pulse between 12 and 3000 ms, followed by a pulse
      interval of 100 ms, resulted into a gradual decrease of ICa during the second
      pulse (180 ms), described by concentration-dependent monoexponential decay curves
      (tau = 1060 +/- 138 ms at 0.3 microM (n = 3); tau = 310 +/- 24 ms at 1 microM (n
      = 6), and tau = 125 +/- 7 ms at 10 microM (n = 5); means +/- SEM). Under control
      conditions, the changes in ICa were comparably negligible. The recovery of ICa
      from block was analyzed by the application of a twin pulse protocol in which two
      depolarising voltage pulses at fixed length (1. pulse at 3 s and 2. pulse at 180
      ms) were interrupted by variable pulse intervals (6 ms-60 s). Under control
      conditions, recovery from inactivation was fast (tau = 11 +/- 0.7 ms; means +/-
      SEM; n = 3). In the presence of verapamil, recovery from block was about 500
      times slower than under control conditions, independent of the drug concentration
      (tau = 5.05 +/- 0.44 s at 0.3 microM (n = 3), tau = 6.7 +/- 0.69 s at 1 microM (n
      = 4), and tau = 6.02 +/- 0.9 s at 10 microM (n = 5); means +/- SEM). Since
      development of block was dependent on the concentration of verapamil, whereas
      recovery from block was independent from the drug concentration, it is assumed
      that the described time constants for block and unblock reflect voltage-dependent
      net binding (tau on) and unbinding (tau off), respectively, of verapamil at its
      receptor sites. A computer simulation, including the time constants of block
      development at 0 mV and of recovery from block at -80 mV, predicted reasonably
      well the observed frequency-dependent block of ICa by verapamil. The development
      of either measured or calculated block of ICa, using 180 ms depolarising voltage
      pulses from -80 mV to 0 mV, was fitted by identical monoexponential association
      curves (tau = 7 s each at 0.2 Hz and tau = 1.7 s each at 1 Hz). When Ba2+ was
      used as the charge carrier, which removes the calcium-dependent inactivation of
      the current, verapamil (3 microM) was less efficient: ICa was decreased by 57 +/-
      6% (means +/- SEM; n = 6), whereas IBa was decreased by 24 +/- 4% (means +/- SEM;
      n = 5). It is proposed that verapamil binds to calcium channels in their
      inactivated state at more positive potentials and dissociates from the channels
      in the resting state at more negative potentials. In the proposed scheme of
      periodical drug binding and unbinding, dependent on the state of the channels,
      the development of frequency-dependent block of ICa by verapamil is adequately
      predicted by the construction of cumulative association/ dissociation curves
      which include the experimentally determined time constants of development and
      recovery from block at 0 mV and -80 mV, respectively.

PMID- 9007847
TI  - Pharmacological differentiation of synergistic contribution of L-type Ca2+
      channels and Na+/H+ exchange to the positive inotropic effect of phenylephrine,
      endothelin-3 and angiotensin II in rabbit ventricular myocardium.
AB  - The present study was designed to delineate pharmacologically the role of
      sarcolemmal L-type Ca2+ channels and Na+/H+ exchange in the positive inotropic
      effect (PIE) of phenylephrine mediated by alpha-1 adrenoceptors, endothelin (ET)
      and angiotensin II (Ang II) that stimulate phosphoinositide (PI) hydrolysis in
      the rabbit ventricular muscle. The PIE of these receptor agonists was compared
      with the PIE of isoprenaline that accumulates cyclic AMP. For this purpose, we
      investigated the influence of a Ca2+ antagonist, verapamil, and of an inhibitor
      of Na+/H+ exchange, 5-(N-ethyl-N-isopropyl) amiloride (EIPA), alone or in
      combination, on the cumulative concentration-response curve (CRC) for
      phenylephrine (with 0.3 microM bupranolol). ET-3 and Ang II in isolated right
      ventricular papillary muscles of the rabbit, which were electrically stimulated
      at 1 Hz in Krebs-Henseleit solution at 37 degrees C. Verapamil at 0.3 and 1
      microM decreased the basal force of contraction to 37.0 +/- 4.0% and 13.2 +/-
      1.1% of the control, respectively, while EIPA event at 10 microM affected the
      basal force to much less extent and decreased it to 87.0 +/- 1.4%. Verapamil (0.3
      and 1 microM) and EIPA (1 and 10 microM), when used alone, each significantly
      attenuated but did not abolish the PIEs induced by phenylephrine, ET-3 and Ang
      II, while the simultaneous administration of verapamil (1 microM) and EIPA (10
      microM) consistently and almost completely inhibited the PIE induced by these
      receptor agonists. By contrast, the PIE of isoprenaline was retained even in the
      presence of verapamil and EIPA. These results indicate that both the influx of
      Ca2+ ions through L-type Ca2+ channels and activation of Na+/ H+ exchange
      contribute synergistically to the PIE that is mediated by alpha-1 adrenergic, ET
      and Ang II receptor agonists, while these mechanisms are not essential for the
      beta-adrenoceptor-mediated PIE.

PMID- 9007848
TI  - Contribution of ATP-sensitive potassium channels to beta-adrenoceptor-mediated
      responses.
AB  - In isolated hearts the inotropic response to the beta-adrenoceptor agonist
      isoproterenol is known to be abolished after ischaemia and reperfusion. The aim
      of this study was to investigate whether at decreased glucose levels the beta
      adrenoceptor-mediated responses in vascular smooth muscle would be depressed,
      since low glucose conditions mimic the influence of ischaemia. Accordingly, we
      investigated the influence of low glucose levels in the extracellular space on
      the vasorelaxation induced by isoproterenol and salbutamol in rat isolated
      thoracic aortic ring preparations with an intact endothelium and we attempted to
      further analyze the underlying mechanisms. Therefore, forskolin, dibutyryl-cAMP
      and glibenclamide (an ATP-sensitive K(+)-channel blocker) were studied as well.
      In a glucose-free medium the concentration-response curve for isoproterenol was
      shifted to the left compared to that obtained under normal glucose conditions.
      The maximal relaxation induced by isoproterenol was not affected by the absence
      of glucose. In contrast, the maximal relaxation induced by salbutamol in glucose
      free medium decreased by 50% compared to that obtained under normal glucose
      conditions. Glibenclamide caused a concentration-dependent decrease of the
      maximum relaxation by isoproterenol in a glucose-free medium, but had no effect
      under normal glucose conditions. Glibenclamide did not influence the
      concentration-response curves for salbutamol, neither in the presence nor in the
      absence of glucose in the medium. The relaxation caused by forskolin and
      dibutyryl-cAMP was not influenced by glibenclamide in a medium devoid of glucose.
      In endothelium-denuded preparations glibenclamide did not affect isoproterenol
      induced responses neither in the presence nor in the absence of glucose. It is
      concluded that beta-adrenoceptor stimulation opens ATP-sensitive potassium
      channels under conditions of impaired ATP-metabolism by a cAMP-independent
      pathway, which needs an intact endothelium.

PMID- 9007849
TI  - Characteristics of palytoxin-induced cation currents and Ca2+ mobilization in
      smooth muscle cells of rabbit portal vein.
AB  - We examined the nature of the palytoxin (PTX)-induced channel and its relevance
      to the Ca2+ mobilizing effect of the toxin on smooth muscle cells isolated from
      rabbit portal vein using whole-cell voltage-clamp and microfluorimetric
      techniques. PTX (1 nM) induced a sustained, irreversible inward current at a
      holding potential of -40 mV. The PTX-induced current reversed at 0.5 +/- 0.6 mV,
      and the PTX-induced channel permitted the passage of Na+, K+, Cs+ and, to a
      lesser extent, Li+, but not choline+ or Ca2+. During the sustained phase of the
      current, superfusion of Ni2+ (5 mM), La3+ (0.5 mM) or 2,4-dichlorobenzamil (2,4
      DCB, 25 microM) reduced the current amplitude and decreased the slope conductance
      without changing the reversal potential. In 5 of 7 experiments, ouabain
      transiently increased the PTX-induced inward current and shifted the reversal
      potential in a positive direction. Subsequently, ouabain inhibited the current in
      every cell. PTX (10 nM) induced a sustained rise in cytosolic Ca2+ ([Ca2+]i),
      which was resistant to verapamil but suppressed by omission of extracellular
      Ca2+. When external Na+ was replaced by choline+, PTX did not increase [Ca2+]i.
      Pretreatment with 2,4-DCB prevented the elevation of [Ca2+]i due to PTX. These
      results suggest that PTX does not directly stimulate Ca2+ entry but induces entry
      through Na(+)-Ca2+ exchange as a consequence of increased cytosolic Na+. Ni2+,
      La3+, 2,4-DCB and ouabain were shown to act as blockers of the PTX-induced
      channel. Ouabain may also inhibit Na+ pump current activated by cytosolic Na+.

PMID- 9007850
TI  - Vascular responses to neuropeptide Y are greater in female than male rats.
AB  - Sex differences in vascular effects of neuropeptide Y (NPY) were investigated in
      isolated tail artery ring segments from male and female F344 rats. Both pre- and
      postjunctional effects of NPY appeared to be greater in females. NPY potentiated
      contractions elicited by transmural adrenergic nerve stimulation (TNS),
      consistent with an effect on smooth muscle Y1 receptors. The degree of
      potentiation was significantly greater in arteries from females than males.
      Ovariectomy of the females resulted in a decrease in potentiation, while
      orchiectomy of the males resulted in an enhanced NPY effect. When NPY
      potentiation was measured in the presence of peptidase inhibitors, the effect of
      exogenous NPY was enhanced; however the enhancement was greater in arteries from
      females than either males or ovariectomized females. Possible male-female
      differences in inhibitory prejunctional Y2 receptor function were addressed using
      the selective agonist NPY13-36. At a low frequency of stimulation (0.5 Hz), NPY13
      36 inhibited the response to TNS in arteries from females and castrated males;
      however, NPY13-36 had no significant effect on responses to TNS in arteries from
      males or ovariectomized females. Thus gonadal hormones appear to modulate several
      components involved in NPY neurotransmission, including tissue peptidase
      activity, postjunctional Y1 and prejunctional Y2 receptors. These effects may
      contribute to significant differences observed in vascular reactivity between
      females and males.

PMID- 9007851
TI  - Contribution of aranidipine metabolites with slow binding kinetics to the
      vasodilating activity of aranidipine.
AB  - Aranidipine, a novel dihydropyridine derivative, gives rise to two active
      metabolites, M-1(alpha) and M-1(beta), which exhibit hypotensive activity
      comparable to that of nifedipine. The aim of this study was to examine the
      recovery phase of the vasodilating effect of M-1(alpha) and of M-1(beta), to
      determine their binding characteristics and to compare the results with those for
      aranidipine and other dihydropyridine derivatives. During intra-arterial infusion
      into the femoral vascular beds of anesthetized dogs, M-1(alpha), M-1(beta), and
      nifedipine, produced increases in femoral blood flow at doses three times higher
      than the dose of aranidipine required to produce a comparable effect. The onset
      and recovery of the effects of the metabolites on femoral blood flow were
      significantly slower than the onset and recovery of the effect of nifedipine. The
      inhibitory activities of M-1(alpha) and M-1(beta) towards stimulated 45Ca uptake
      in isolated guinea pig aorta were less than that of aranidipine. In binding
      studies, using porcine heart membrane preparations, [3H]M-1(alpha) and [3H]M
      1(beta) had larger Kd values than [3H]aranidipine and [3H]nitrendipine, but the
      maximal binding number for each of them was almost the same. The association and
      dissociation rate constants for [3H]M-1(alpha) and [3H]M-1(beta) binding, as well
      as those for [3H]aranidipine binding, were significantly smaller than those for
      [3H]nitrendipine, corresponding to the recovery of the in vivo vasodilating
      effects of the metabolites. The dissociation rate constants of these radiolabeled
      ligands were highly positively correlated with the elimination rate constants of
      their in vivo vasodilating effects. From these results, we conclude that M
      1(alpha) and M-1(beta), although their binding affinities and Ca2+ antagonistic
      actions are less potent, possess slower kinetic binding properties than many
      other dihydropyridines and that the slow kinetic interaction of these metabolites
      with the dihydropyridine receptor may contribute to the long-lasting in vivo
      vasodilating effect of aranidipine.

PMID- 9007852
TI  - Effects of alpha-tocopherol on nerve conduction velocity and regeneration
      following a freeze lesion in immature diabetic rats.
AB  - We investigated whether anti-oxidant treatment with alpha-tocopherol (1 g kg-1
      day-1) could prevent the blunting of the normal maturational increase in motor
      and sensory nerve conduction velocity when diabetes is induced by streptozotocin
      in young rats. A further study in the same rats examined effects on myelinated
      fibre regeneration distance 14 days after a punctate sciatic nerve lesion by a
      liquid nitrogen cooled probe. In non-diabetic rats between 8 and 14 weeks of age,
      sciatic motor and saphenous sensory conduction velocity increased by
      approximately 28% (P < 0.001) and 21% (P < 0.001) respectively. Diabetes induced
      at 8 weeks blunted this maturational change by 65% for sciatic motor and almost
      completely for saphenous sensory fibres (P < 0.001). Treatment with alpha
      tocopherol from diabetes induction totally prevented motor conduction velocity
      deficits (P < 0.001). For sensory saphenous nerve, conduction abnormalities were
      markedly attenuated (72%, P < 0.001) although a significant deficit remained
      compared to age-matched non-diabetic rats (P < 0.01). Sciatic nerve myelinated
      fibre regeneration distance, 14 days post lesion, was 15% reduced (P < 0.001) by
      untreated diabetes. However, in diabetic rats treated with alpha-tocopherol,
      regeneration distance was significantly improved (P < 0.001), being within the
      non-diabetic range. Thus, the data highlight the importance of reactive oxygen
      species in the aetiology of impaired nerve maturation and regeneration in
      experimental diabetes and indirectly support the view that anti-oxidant treatment
      could have a therapeutic role in patients.

PMID- 9007854
TI  - Complications of transsphenoidal surgery: results of a national survey, review of
      the literature, and personal experience.
AB  - OBJECTIVE: The primary objectives of this report were, first, to determine the
      number and incidence of complications of transsphenoidal surgery performed by a
      cross-section of neurosurgeons in the United States and, second, to ascertain the
      influence of the surgeon's experience with the procedure on the occurrence of
      these complications. The secondary objective was to review complications of
      transsphenoidal surgery from the standpoint of their causation, treatment, and
      prevention. METHODS: Questionnaires regarding 14 specific complications of
      transsphenoidal surgery were mailed to 3172 neurosurgeons. The data reported were
      analyzed from the 958 respondents (82%) who reported performing the operation.
      The neurosurgeons surveyed were asked to estimate the number of transsphenoidal
      operations performed, to identify any complications observed, and to estimate the
      percentage of operations that had resulted in any of the 14 specific
      complications. The 958 respondents were placed into three experience groups,
      based on the number of transsphenoidal operations performed. The data were
      analyzed by using chi 2 tests and Spearman correlation coefficients. The
      secondary objectives were met through a detailed review of the literature, in
      light of our experience. RESULTS: Of the respondents, 87.3% reported having
      performed < 200 operations and 9.7% reported 200 to 500 previous operations. The
      remaining 3% reported more than 500 previous operations. More extensive previous
      experience with transsphenoidal surgery was associated with a greater likelihood
      of having witnessed each specific complication. The mean operative mortality rate
      for all three groups was 0.9%. Anterior pituitary insufficiency (19.4%) and
      diabetes insipidus (17.8%) were complications with the highest incidence of
      occurrence. The overall incidence of cerebrospinal fluid fistulas was 3.9%. Other
      significant complications, such as carotid artery injuries, hypothalamic
      injuries, loss of vision, and meningitis, occurred with incidence rates between 1
      and 2%. An inverse relationship was found between the experience group and the
      likelihood of complications, as indicated by significant negative Spearman
      correlation coefficients for all but 2 of the 14 complications listed in the
      survey (P < 0.05). Thus, increased experience with transsphenoidal surgery seems
      to be associated with a decreased percentage of operations resulting in
      complications. Some caution should be exercised in interpreting these data,
      because they are based on the respondents' estimates. CONCLUSION: Transsphenoidal
      surgery seems to be a reasonably safe procedure, with a mortality rate of less
      than 1%. However, a significant number of complications do occur. The incidence
      of these complications seems to be higher, with statistical significance, in the
      hands of less experienced surgeons. The learning curve seems to be relatively
      shallow, because a statistically significantly decreased incidence of morbidity
      and death could be documented after 200 and even 500 transsphenoidal operations.
      Better understanding of the indications for transsphenoidal surgery and improved
      familiarity with the regional anatomy should further lower the incidence of death
      and morbidity resulting from this procedure in the hands of all neurosurgeons.

PMID- 9007853
TI  - [3H]2-(2-Benzofuranyl)-2-imidazoline, a highly selective radioligand for I2
      imidazoline receptor binding sites. Studies in rabbit kidney membranes.
AB  - 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) has recently been characterised as a
      selective ligand for the I2-type of imidazoline-receptor binding site(s) (I2
      RBS). The present studies determined the relative levels of specific [3H]2-BFI
      binding to membrane homogenates of brain and kidney from rat, guinea pig and
      rabbit and identified the pharmacological characteristics of [3H]2-BFI binding
      sites in rabbit kidney membranes. Rabbit kidney membranes had the highest
      relative density of specific [3H]2-BFI binding of all tissues studied (2000
      fmol/mg protein). Rabbit brain and guinea pig kidney had moderate levels of
      specific [3H]2-BFI binding (350-500 fmol/mg protein), while rat kidney and guinea
      pig and rat brain displayed much lower densities of binding (40-65 fmol/mg
      protein). Studies of [3H]2-BFI binding kinetics in rabbit kidney homogenates
      revealed binding to two distinct sites with Kd values of 0.10 +/- 0.01 nmol/l and
      1.00 +/- 0.36 nmol/l respectively. Equilibrium saturation studies were also
      consistent with the presence of two binding sites-[3H]2-BFI (0.01-20 nmol/l)
      bound to sites with affinities of 0.10 +/- 0.01 nmol/l and 0.92 +/- 0.13 nmol/l
      and binding densities of 470 +/- 80 and 840 +/- 60 fmol/mg protein (n = 3),
      representing 36 and 64% respectively. Drug inhibition studies revealed that L
      adrenaline; alpha 1-adrenoceptor drugs (prazosin, L-phenylephrine) and alpha 2
      adrenoceptor drugs (rauwolscine, methoxyidazoxan, 2-(2,4-(O-methoxyphenyl)
      piperazin-1-yl)-ethyl-4, 4-dimethyl-1,3-(2H,4H)-isoquinolindione (ARC-239) had
      extremely low affinities for [3H]2-BFI binding sites (IC50 > or = 10 mumol/l).
      Putative I1-RBS compounds, p-aminoclonidine, moxonidine, imidazole-4-acetic acid
      and cimetidine, inhibited [3H]2-BFI binding to rabbit renal membranes with low to
      very low affinities (Ki values 3 to > or = 100 mumol/l), suggesting [3H]2-BFI
      does not label I1-RBS in rabbit kidney membranes. I2-RBS compounds-2- (4,5
      dihydroimidaz-2-yl)-quinoline (BU224), 2-(4,5-dihydroimidaz-2-yl)-quinoxaline
      (BU239), idazoxan and cirazoline-potently inhibited [3H]2-BFI binding (Ki values
      0.37-1.6 nmol/l), confirming the labelling of I2-RBS. Inhibition of [3H]2-BFI
      binding by certain compounds was consistent with their interaction with two
      binding site populations-for example (drug, Ki values) guanabenz, 0.65 nmol/l and
      0.17 mumol/l; naphazoline, 0.94 nmol/l and 2.8 mumol/l; amiloride, 76 nmol/l and
      26 mumol/l rilmenidine, 150 nmol/l and 50 mumol/l; and clonidine, 230 nmol/l and
      70 mumol/l. The high affinity of amiloride for a high proportion (85%) of the
      binding is consistent with the presence of the I2A-subtype of I-RBS in rabbit
      kidney. These results demonstrate that [3H]2-BFI is a highly selective and high
      affinity radioligand for I2-RBS which should be useful for the further
      characterisation of these sites in mammalian tissues.

PMID- 9007856
TI  - Management of 1000 vestibular schwannomas (acoustic neuromas): hearing function
      in 1000 tumor resections.
AB  - OBJECTIVE: The realistic chances of hearing preservation and the comparability of
      international results on hearing preservation in complete microsurgical
      vestibular schwannoma resections were the focus of this study in a large patient
      population treated by uniform principles. METHODS: One thousand vestibular
      schwannomas were operated on at Nordstadt Neurosurgical Department, from 1978 to
      1993, by the senior surgeon (MS). There were 1000 tumors in 962 patients, i.e.,
      880 patients with unilateral tumors and 82 patients operated on for bilateral
      tumors in neurofibromatosis-2 (120 cases). Preservation of the cochlear nerve was
      attempted whenever possible. The audiometric data were analyzed by the Nordstadt
      classification system and graded in steps of 30 dB by audiometry and in steps of
      10 to 30% by speech discrimination; for comparability, the data were also
      evaluated by the criteria of Gardner, Shelton, and House, and they were assessed
      in relation to the Hannover tumor extension grading system. RESULTS: Anatomic
      cochlear nerve preservation was achieved in 682 of 1000 cases (68%), as well as
      in some preoperatively deaf patients, a very few of whom regained some hearing.
      Of a total of 732 cases with some preoperative hearing, anatomic cochlear nerve
      preservation was achieved in 580 cases (79%) and functional cochlear nerve
      preservation in 289 (39.5%); analysis over time revealed an actual preservation
      rate of 47% in the most recent 200 cases. Specific factors, such as gender, tumor
      extension, preoperative hearing quality, and symptom duration, were investigated
      for their predictive value for hearing preservation. Male gender, small to medium
      tumor size (mainly extending within the cerebellopontine cistern; Classes T2 and
      T3), good to moderate hearing (up to 40-dB loss), and short duration of
      hypoacusis (< 1.5 yr) or of vestibular disturbances (< 0.7 yr) were advantageous
      factors, with chances of hearing preservation between 47 and 88%. CONCLUSION:
      Functional cochlear nerve preservation in complete microsurgical resection should
      belong to the contemporary standard of treatment goals.

PMID- 9007855
TI  - The surgical resectability of meningiomas of the cavernous sinus.
AB  - OBJECTIVE: The optimal management for patients with cavernous sinus meningiomas
      remains controversial. We attempt to contribute to the ongoing debate of
      appropriate surgical indications. METHODS: In this retrospective review, 39
      patients, including 27 women and 12 men ranging in age from 24 to 73 years
      (median, 48 yr), underwent surgical treatment for this condition. Completeness of
      tumor resection, cranial nerve morbidity, general morbidity, and long-term
      outcome were studied. The cavernous internal carotid artery was partially encased
      in 15 patients, totally encased in 11 patients, and narrowed by tumor in 13
      patients. RESULTS: Of eight patients who underwent complete tumor resection,
      seven had partial encasement of the internal carotid artery. Of 31 patients who
      underwent subtotal resection, 11 underwent postoperative radiotherapy. There were
      no deaths in the series. Morbidity was 17.9% for cranial nerves controlling
      extraocular motor function. Trigeminal nerve function did not improve after
      surgical treatment. The median follow-up period was 2 years (range, 6 mo-5.3 yr).
      Symptomatic and radiographic recurrence occurred in two patients who underwent
      complete tumor resection and in two patients who underwent subtotal resection.
      CONCLUSION: Based on our findings and a review of the literature, we conclude the
      following: 1) the resectability of meningiomas of the cavernous sinus depends on
      the degree of internal carotid artery involvement; 2) total excision of cavernous
      sinus meningiomas is possible but rarely achieved in holocavernous meningiomas;
      3) cranial nerve morbidity is significant; and 4) subtotal excision with or
      without postoperative radiotherapy is an effective short-term oncological
      strategy.

PMID- 9007857
TI  - Cystic craniopharyngioma: long-term results after intracavitary irradiation with
      stereotactically applied colloidal beta-emitting radioactive sources.
AB  - OBJECTIVE: Long-term follow-up data were analyzed to assess the value of
      intracavitary irradiation with stereotactically applied beta-emitting
      radioisotopes for the treatment of craniopharyngioma cysts. METHODS: Sixty-two of
      70 consecutive patients with predominantly cystic craniopharyngiomas were
      selected for retrospective analysis. Beta-Emitting isotopes were injected
      intracystically using a computed tomography-guided and computer-assisted three
      dimensional stereotactic treatment planning and application system (cumulative
      dose to the inner surface of the cyst wall, 200 Gy). RESULTS: The tumor response
      rate gained with yttrium-90-labeled silicate (66 of 78 cysts) or phosphorous-32
      labeled chromic phosphate (8 of 78 cysts) was 79.5%. Four cysts treated with
      rhenium-186-labeled sulfate did not respond. Mean survival after intracavitary
      irradiation was 9.0 +/- 0.9 years (median follow-up, 11.9 yr). In patients with
      solitary cysts, the mean survival was 12.5 +/- 1.4 years (actuarial 5- and 10-yr
      survival rates, 80 and 64%, respectively). Six months postoperatively, visual
      deficits (38 of 62 patients) had improved in 23 patients and were stable in 15
      patients. The side effects that occurred 6 to 12 months after treatment with
      yttrium-90 were complete blindness (three patients), worsening of visual field
      cuts (one patient), third nerve palsy (one patient), and diabetes insipidus
      and/or panhypopituitarism (three patients). CONCLUSIONS: Intracavitary
      irradiation using yttrium-90 or phosphorous-32 is highly effective in the
      treatment of cystic craniopharyngiomas. If applied as initial treatment in
      patients with solitary cysts, it is the only required therapy over a long period.

PMID- 9007858
TI  - The treatment of recurrent unresectable and malignant meningiomas with interferon
      alpha-2B.
AB  - OBJECTIVE: Recurrent malignant meningiomas and unresectable meningiomas represent
      a great therapeutic challenge after the failure of radiation therapy. No
      effective chemotherapy has been found. We report the preliminary results of the
      treatment of patients with recurrent unresectable or malignant meningiomas with
      recombinant interferon alpha-2B (IFN-alpha-2B). METHOD: Each of six patients with
      either a recurrent malignant meningioma or an unresectable meningioma was treated
      with IFN-alpha, administered subcutaneously at a dosage of 4 mU/m2 per day, 5
      days per week. Two of the six meningiomas were regular, one was atypical, and
      three were malignant. RESULTS: Five of six patients exhibited positive response
      to treatment; with stabilization of the size of the tumor in four patients and
      slight regression in one. The responses observed lasted from 6 to 14 months. The
      toxicity associated with prolonged use of IFN-alpha was mild and well tolerated.
      CONCLUSION: These results suggest that IFN-alpha is effective in the treatment of
      recurrent malignant meningiomas.

PMID- 9007859
TI  - The in vivo metabolic pattern of low-grade brain gliomas: a positron emission
      tomographic study using 18F-fluorodeoxyglucose and 11C-L-methylmethionine.
AB  - OBJECTIVE: The object of the present study was to identify metabolic differences
      between low-grade astrocytomas and oligodendrogliomas and to improve their
      diagnosis and noninvasive assessment, because both types of tumors look very
      similar from the point of view of clinical and radiological data (as assessed by
      computed tomography and magnetic resonance imaging). METHODS: Before any
      aggressive treatment, 22 patients with primary low-grade gliomas (astrocytomas in
      12 patients and oligodendrogliomas in 10) were investigated with positron
      emission tomography for both glucose metabolism (18F-fluorodeoxyglucose) and
      amino acid uptake (11C-L-methylmethionine). An original software that allows a
      full metabolic analysis of the tumor region of interest (defined from the T1
      weighted magnetic resonance image) and compares tumor tissue uptake tracer
      concentrations with average healthy tissue values has been implemented for data
      processing. Heterogeneity of each individual tumor has been taken into account
      and was expressed in histograms, which provided data about the mean and also
      extreme and intermediate values of tracer concentrations and the way these values
      are distributed among the full tumor mass. RESULTS: It has been shown that both
      tumor types exhibit a glucose hypometabolism (slightly more pronounced with
      astrocytomas), whereas they strongly differ in methionine uptake, which is high
      in all oligodendrogliomas and either decreased, normal, or moderately increased
      in astrocytomas. This latter metabolic difference between both tumor populations
      may be partially explained by their different cell densities. CONCLUSION: This
      study suggests that despite similar radiological and clinical presentations,
      these two kinds of low-grade gliomas are metabolically different and could
      therefore have specific responses to different therapies. Moreover, their in vivo
      metabolic follow-up with positron emission tomography should rely on different
      parameters, depending on their histological type; methionine uptake may be more
      relevant than glucose metabolism in the follow-up of oligodendrogliomas.

PMID- 9007861
TI  - Brain tissue gases and pH during arteriovenous malformation resection.
AB  - OBJECTIVE: The purpose of this study was to determine whether baseline partial
      pressure of oxygen (PO2), partial carbon dioxide pressure (PCO2), and pH in brain
      tissue adjacent to arteriovenous malformations (AVMs) are different from those in
      control patients. In addition, PO2, PCO2, and pH changes were measured during
      resection of the AVMs. METHODS: Two groups were studied. Group 1 (n = 8) was
      composed of nonischemic patients scheduled for cerebral aneurysm clipping. Group
      2 (n = 13) was composed of patients undergoing neurosurgery for resection of
      AVMs. After the craniotomy, the dura was retracted and a combined PO2, PCO2, and
      pH sensor was inserted into nonischemic brain tissue in Group 1. In Group 2, the
      sensor was inserted into tissue 2 to 3 cm from the margin of the AVMs, within the
      same arterial blood supply. After equilibration of the sensor, tissue gases and
      pH were measured during steady-state anesthetic conditions in Group 1 and during
      resection of AVMs in Group 2. RESULTS: Under baseline conditions before the start
      of surgery, tissue PO2 was decreased in patients with AVMs compared with control
      patients, but PCO2 and pH were not changed. During resection of the AVMs, PO2 and
      pH increased and PCO2 decreased compared with baseline measurements. These
      parameters did not change in control patients during a similar time period.
      CONCLUSION: The results suggest that cerebrovascular or metabolic adaptation
      occurs in patients with AVMs with decreased tissue perfusion pressure as an
      adjustment for decreased oxygen delivery. During resection of AVMs, this
      adaptation produces a relative hyperemic environment with tissue hyperoxia,
      hypocapnia, and alkalosis that is not corrected by the end of surgery.

PMID- 9007860
TI  - The safety and efficacy of cyclosporine A in the prevention of vasospasm in
      patients with Fisher grade 3 subarachnoid hemorrhages: a pilot study.
AB  - OBJECTIVE: To evaluate the safety and any potential effect of cyclosporine A
      (CycA) in preventing cerebral vasospasm. METHODS: Nine patients with Fisher Grade
      3 subarachnoid hemorrhages were studied. After a loading dose of 7.5 mg/kg of
      CycA was administered every 12 hours for two doses, enteral treatment with CycA
      was started within 72 hours of the onset of the subarachnoid hemorrhage. Whole
      blood CycA levels were titrated to maintain levels of 50 to 400 ng/kg.
      Transcranial doppler ultrasonography was performed daily. Middle cerebral artery
      velocities were used to assess the degree of vasospasm. Angiography was performed
      to confirm the vasospasm in symptomatic patients, or it was performed if
      transcranial doppler ultrasonograms were unobtainable. Patients were treated with
      a standard pharmacological regimen of nimodipine. Induced hypertension,
      hemodilution, and hypervolemia were instituted at the discretion of the
      neurosurgical team. Intra-arterial papaverine was infused into the vasospastic
      vessels of three recalcitrant patients. Outcome was assessed at 6 months with the
      Glasgow Outcome Scale. RESULTS: All the patients displayed evidence of vessel
      narrowing, which was disclosed by transcranial doppler ultrasonography or
      angiography. Five patients developed ischemic deficits, two were treated with
      intra-arterial papaverine, and three died of complications secondary to
      vasospasm. No significant hepatic, renal, or infectious complication developed as
      a result of the administration of CycA. CONCLUSIONS: CycA proved safe to use but
      failed to prevent the development of cerebral vasospasm or delayed ischemic
      deficits in patients considered at high risk.

PMID- 9007862
TI  - The predictive value of intraoperative electrocorticography in resections for
      limbic epilepsy associated with mesial temporal sclerosis.
AB  - OBJECTIVE: Prior studies on the predictive value of intraoperative
      electrocorticography (ECoG) have been performed on heterogeneous groups of
      patients with both temporal and extratemporal interictal spikes, lesional and
      nonlesional pathological findings, and variably extensive resections by different
      surgeons. METHODS: We performed both pre- and postresection intraoperative ECoG
      on 29 consecutive patients with medial temporal lobe epilepsy (17 left-sided) who
      underwent standard nontailored resections by one surgeon (RRG). All patients had
      only temporal interictal spikes (six bitemporal) and mesial temporal sclerosis
      diagnosed by preoperative magnetic resonance imaging and confirmed by
      pathological examination of resected tissue. RESULTS: After a mean follow-up of
      24.8 months, there were 15 (52%) patients who were seizure-free, 6 (21%) who were
      seizure-free except for auras, and 8 (28%) who had any seizure after the 1st
      postoperative month. Fourteen patients (48%) had active interictal discharges
      outside the area of planned resection revealed by preresection ECoG. Neither the
      presence of these spikes nor their mean frequency correlated with seizure
      outcome. Eleven patients (38%) had residual spike discharges after resection, and
      18 patients (62%) had new spikes revealed by the postresection ECoG. Neither of
      these findings nor the mean spike frequency of residual or new spikes related to
      seizure outcome. Persistent spikes increased in frequency after resection in all
      outcome groups. CONCLUSIONS: Electrocorticographic monitoring of interictal
      epileptiform activity intraoperatively is not useful in the surgical treatment of
      patients undergoing standard resection for medial temporal lobe epilepsy with
      magnetic resonance imaging evidence of mesial temporal sclerosis.

PMID- 9007863
TI  - Validation study of a central venous pressure-based protocol for the management
      of neurosurgical patients with hyponatremia and natriuresis.
AB  - OBJECTIVE: We had previously suggested a protocol for the management of
      neurosurgical patients with hyponatremia and natriuresis that was based on their
      volume status as determined by actual blood volume measurements. All patients in
      that study were found to be hypovolemic or normovolemic and responded, within 72
      hours, to salt and fluid replacement. In the present study, the validity of that
      protocol was tested using central venous pressure as the sole measure of volume
      status of patients with hyponatremia and natriuresis. METHOD: Twenty-five
      consecutive patients (26 cases) who fulfilled the inclusion criteria typically
      used to diagnose the syndrome of inappropriate secretion of antidiuretic hormone
      were included in the study. Central venous pressure was used to classify patients
      as hypovolemic (< 5 cm of water), normovolemic (6-10 cm of water), or
      hypervolemic (> 11 cm of water). Hypovolemic patients were given fluids (50
      ml/kg/d) and salt (12 g/d). Normovolemic patients were given normal fluid with 12
      g of salt per day. In addition, patients with anemia (hematocrit, < 27%) were
      administered whole blood. The end point was a serum sodium of more than or equal
      to 130 mEq/L measured in two consecutive samples 12 hours apart or 72 hours after
      entry into the study. If the serum sodium was less than 130 mEq/L at the end of
      72 hours, the clinical condition of the patient determined further management.
      RESULTS: Nineteen of 25 patients (26 cases) were hypovolemic, the rest were
      normovolemic. No patient was hypervolemic. Nineteen of 25 patients (26 cases)
      attained normal serum sodium values within 72 hours, and an additional 3
      responded within the next 36 hours (108 h after entry into the study). One
      patient who was discharged on request had normalized her serum sodium a week
      later. Among the three nonresponders, who were severely hypovolemic, as revealed
      by blood volume measurement, and responded to increased fluid and salt
      administration. One was normovolemic and responded to increased salt
      administration. There were no complications related to the therapy. CONCLUSION:
      Hyponatremia with natriuresis in the neurosurgical setting responds to salt and
      fluid replacement guided by the patients' volume status as determined by the
      central venous pressure. This study also offers further indirect evidence to
      suggest that the syndrome of hyponatremia with natriuresis is most often caused
      by "cerebral salt wasting" rather than by the syndrome of inappropriate secretion
      of antidiuretic hormone.

PMID- 9007864
TI  - A comparative study of intracranial aneurysm clips: closing and opening forces
      and physical endurance.
AB  - OBJECTIVE: The closing and opening forces of various types of intracranial
      aneurysm clips were measured, and the physical endurance of the clips was
      evaluated. METHODS: Straight, bayonet, angled, fenestrated, and temporary Sugita
      and Yasargil clips were tested by measuring the forces exerted by the blades as
      they were opened in wider increments and at various points along their length by
      a specially designed clip tester. Closing forces after repeated openings,
      continuous opening, or multiple sterilization procedures also were measured.
      RESULTS: The opening forces of Yasargil clips increased linearly and more sharply
      as the blades were opened wider than those of Sugita clips. Only Sugita clips
      showed significant differences between the opening and closing forces
      (hysteresis). Closing forces of all of the tested clips were according to a
      hyperbolic curve. Straight clips showed a sharper rise in closing forces than
      those of bayonet, angled, or fenestrated clips. A relatively weak closing force
      at the tip of Yasargil long clips and a strong closing force at the base of
      temporary clips were unexpected findings. The closing force decreased by only 3
      to 7% after 500 openings and did not decrease after continuous opening for 17
      hours or 100 sterilization procedures. CONCLUSION: Our study showed that the
      closing forces differed depending not only on the distance of the point of
      measurement from the clip spring but also on the shapes of the clip blades.
      Repeated opening or sterilization of the clips did not significantly decrease the
      closing forces of the aneurysm clips.

PMID- 9007865
TI  - Surgical treatment for pediatric moyamoya disease: use of the superficial
      temporal artery for both areas supplied by the anterior and middle cerebral
      arteries.
AB  - OBJECTIVE: To revascularize ischemic territories of both the anterior cerebral
      artery (ACA) and the middle cerebral artery (MCA), a simple and effective
      combined bypass operation was performed in 36 pediatric patients with moyamoya
      disease during the past 8 years. METHODS: The branches of the superficial
      temporal artery (STA) were used to revascularize the ACA and MCA territories. In
      children older than 5 years, the parietal branch of the STA was usually used for
      an end to side anastomosis with a cortical branch of the MCA. In children who
      were younger than 5 years, the parietal branch of the STA was used for an
      encephaloduroarteriosynangiosis instead of a direct anastomosis.
      Encephaloduroarteriosynangiosis, using the proximal part of the intact frontal
      branch of the STA, and encephalomyosynangiosis, using the temporal muscle, were
      also performed in all patients to stimulate spontaneous anastomosis. In addition,
      bilateral frontal burr holes were made in all patients to induce vascularization
      of the ACA territories from the distal part of the intact frontal branch of the
      STA. The first operation was performed on the dominant side, then a similar
      procedure was performed on the opposite side after an interval of at least 3
      months. RESULTS: Postoperative clinical symptoms and the findings from magnetic
      resonance imaging, magnetic resonance angiography, angiography, and
      electroencephalography demonstrated improvement in all patients. CONCLUSION:
      These results suggest that the placement of bilateral burr holes (while leaving
      the frontal branch of the STA intact), in addition to the STA-MCA anastomosis,
      encephaloduroarteriosynangiosis, and encephalomyosynangiosis, is very effective
      in vascularizing the ischemic ACA and MCA territories in pediatric patients with
      moyamoya disease.

PMID- 9007866
TI  - Brain stem involvement in children with neurofibromatosis type 1: role of
      magnetic resonance imaging and spectroscopy in the distinction from diffuse
      pontine glioma.
AB  - OBJECTIVE: To evaluate the ability of magnetic resonance imaging (MRI) and proton
      magnetic resonance spectroscopy (MRS) to distinguish neurofibromatosis Type 1 (NF
      1) with brain stem enlargement from diffuse pontine glioma (PG) in pediatric
      patients. METHODS: A chart review was used to identify all patients with NF-1 and
      diffuse brain stem enlargement who were seen at our institution and who had
      undergone MRI. Comparison groups were as follows: 1) eight patients who did not
      have NF-1 but who did have diffuse PG, and 2) seven healthy children. Midsagittal
      diameters of the pons, midbrain, and medulla were measured in all patients, and
      the results were statistically analyzed. Two MRS variables were also
      statistically compared: N-acetyl aspartate and the vector sum of the metabolites
      choline and creatine/phosphocreatine. RESULTS: In MRI-based measurements, only
      the pontine midsagittal diameter differed significantly between the NF-1 and PG
      groups (P = 0.002). Altogether, 21 children underwent MRS, including 6 in the NF
      1 group. Measures of both MRS variables were significantly lower in patients with
      PG than in the others (P < or = 0.007). The two MRS variables classified the 21
      children into the three respective groups with 100% accuracy. Of the seven
      patients with NF-1, four presented with symptoms attributable to brain stem
      involvement. The brain stems of all seven patients with NF-1 were hyperintense on
      T2-weighted magnetic resonance images, and five were isointense on T1-weighted
      images; only one exophytic tumor was identified. Four of the patients with NF-1
      were followed up clinically without treatment; all remained alive and
      neurologically stable for a median of 40 months. All eight patients in the PG
      group were symptomatic at presentation, and all except one died despite therapy.
      CONCLUSION: Both MRI measurements and MRS seem to be useful for distinguishing
      patients with NF-1 and diffuse brain stem enlargement from patients without NF-1
      but with diffuse PG. They should be most helpful in differentiating symptomatic
      patients with NF-1 from patients with PG, thereby minimizing aggressive treatment
      and its side effects in patients destined to have better outcomes.

PMID- 9007867
TI  - The efficient calculation of neurosurgically relevant volumes from computed
      tomographic scans using Cavalieri's Direct Estimator.
AB  - OBJECTIVE: Because decision making in the daily practice of neurosurgery requires
      judgments about changes in the volume of spatially complex three-dimensional
      objects, we sought a simple, rapid, and accurate method for extracting this
      information from standard computed tomographic (CT) scans. METHODS: Volume
      measurements were made by using a transparent template to overlay a grid of
      regularly-spaced points over CT scans of randomly selected patients with
      hydrocephalus or malignant gliomas. The volume of an object appearing on a scan
      is the product of the sum of points that fell on the object, the area associated
      with each point, and the distance between scan slices. This method is known as
      the Cavalieri Direct Estimator. We assessed the potential clinical applicability
      of this technique by measuring interobserver correlation for ventricular volume
      measurements in hydrocephalic patients, correlating brain tumor volume
      measurements with those obtained using the ISG Allegro system (ISG Technologies,
      Inc., Mississauga, Ontario) (a three-dimensional reconstruction software
      package), and measuring the time required for volumetric analyses. RESULTS: Tumor
      volume estimates using this method correlated highly (r = 0.999) with those made
      by the ISG Allegro System. Interobserver correlation for ventricular volume
      estimates was also high (r = 0.968). We found that the time required for
      application of this technique to CT scans ranged from 4 to 10 minutes.
      CONCLUSIONS: We conclude that the Cavalieri Direct Estimator can be easily
      applied to acquire volume measurements from standard CT scans and requires only a
      few minutes and no additional expense, making it ideal for daily use in clinical
      practice.

PMID- 9007868
TI  - Carotid angioplasty and stent: an alternative to carotid endarterectomy.

PMID- 9007869
TI  - Presence of contractile endothelin-A and dilatory endothelin-B receptors in human
      cerebral arteries.
AB  - OBJECTIVE: The aim of the present study was to elucidate the endothelin receptor
      subtypes responsible for the endothelin-induced vasomotor responses of human
      cerebral arteries. METHODS: Human cerebral arteries with endothelium were mounted
      in in vitro tissue baths, and the vascular responses to endothelin-1 (ET-1) and
      sarafotoxin 6c (a selective ETB agonist) were studied in the presence or absence
      of endothelin blockers, bosentan (Ro 47-0203), a novel nonpeptide ETA and ETB
      receptor antagonist, and FR139317, a selective ETA receptor antagonist. The
      presence of messenger ribonucleic acid encoding the human ETA and ETB receptors
      in human cerebral arteries with intact endothelium and in segments denuded of
      endothelium was studied by the use of reverse transcriptase-polymerase chain
      reaction. RESULTS: ET-1 induced concentration-dependent contraction of human
      cerebral arteries; the pEC50 value was 9.4 +/- 0.2. The vasoconstriction was
      significantly antagonized both by bosentan and by FR139317. The pA2 values were
      7.2 +/- 0.4 and 7.4 +/- 0.4, respectively. Sarafotoxin 6c failed to cause
      contraction of human cerebral arteries. In precontracted vessels, however,
      sarafotoxin 6c induced dilatation that was significantly inhibited by bosentan
      (10 mumol/L), resulting in a pA2 value of 6.0 +/- 0.2. Furthermore, messenger
      ribonucleic acid encoding the human ETA and ETB receptors was detected in human
      cerebral arteries both with and without endothelium. CONCLUSION: The ET-1-induced
      vasoconstriction of human cerebral arteries is primarily mediated by the ETA
      receptor, whereas the sarafotoxin 6c-induced vasodilatation seems to be mediated
      via the ETB receptor.

PMID- 9007870
TI  - Prevention of chronic cerebral vasospasm in dogs with milrinone.
AB  - OBJECTIVE: Delayed cerebral ischemia resulting from vasospasm is a major cause of
      morbidity and death in patients with aneurysmal subarachnoid hemorrhage.
      Milrinone, because it inhibits Type IV cyclic adenosine monophosphate-specific
      phosphodiesterase enzyme in both cardiac and vascular smooth muscle, is a
      powerful inotrope and vasodilator, but it has little effect on heart rate or
      blood pressure. Because of these properties, milrinone is an attractive potential
      therapy after subarachnoid hemorrhage. The purpose of the present study was to
      investigate the effect of milrinone on chronic experimental cerebral vasospasm.
      METHODS: A double-hemorrhage canine model of vasospasm was used to study the
      efficacy of milrinone. Angiographic vasospasm and systemic hemodynamics were
      compared in a treatment group of animals that received a loading dose of
      milrinone (0.05 mg/kg, intravenously) and then slow-release (0.05
      microgram/kg/min) milrinone pellets (n = 10) and a control group that received
      placebo pellets (n = 9), over an 8-day period after the initial subarachnoid
      hemorrhage. The hemorrhage was created by injection of 4 ml of autologous,
      nonheparinized, arterial blood into the cisterna magna on Days 1 and 3.
      Hemodynamic measurements, including cardiac output determinations, were made on
      Days 0, 1, 3, 6, and 8 with a pulmonary artery catheter, and angiographic
      vasospasm was assessed on Day 8 by comparison with baseline angiograms. RESULTS:
      Treatment with milrinone caused no significant changes in systemic hemodynamics.
      Angiographic vasospasm, however, was significantly reduced in the Day 8
      angiograms for the treated group, compared with the control group (98.28 +/-
      14.06 and 67.89 +/- 13.06% of original vessel cross-sectional area, respectively;
      P < 0.001). CONCLUSION: Milrinone is effective in preventing chronic cerebral
      vasospasm in a canine model of experimental chronic cerebral vasospasm. This
      effect is independent of changes in systemic hemodynamics. Milrinone and related
      drugs warrant further investigation for the treatment of cerebral vasospasm.

PMID- 9007871
TI  - Protective effects of ifenprodil on ischemic injury size, blood-brain barrier
      breakdown, and edema formation in focal cerebral ischemia.
AB  - OBJECTIVE: Ifenprodil, a polyamine site N-methyl-D-aspartate receptor/channel
      antagonist, has been reported to decrease infarction volume after cerebral
      ischemia. However, the possible mechanisms of this protective effect have not
      been studied in detail. We investigated the effects of ifenprodil on ischemic
      injury size, blood-brain barrier (BBB) permeability, regional brain edema, and
      cerebral blood flow. METHODS: Focal ischemia for 6 hours was produced by
      permanent occlusion of the middle cerebral artery in 15 anesthetized cats.
      Treatment with drug (n = 8) or vehicle (n = 7) was initiated at 5 minutes after
      ischemia and continued for 3 hours. Physiological variables were continuously
      monitored during experiments. We measured ischemic injury size, brain edema, and
      BBB permeability to Evans blue and determined regional cerebral blood flow by
      using laser doppler flowmetry. RESULTS: Both ischemic injury size and BBB
      permeability were smaller in the ifenprodil-treated group, compared with the
      saline-treated group (P < 0.05). Ifenprodil treatment also attenuated brain edema
      formation in the dense ischemic region, compared with saline treatment (1.035 +/-
      0.002 versus 1.028 +/- 0.002, P < 0.05). There was no significant change in
      cerebral blood flow with ifenprodil treatment. CONCLUSION: Findings from this
      study confirm that ifenprodil treatment results in a significant decrease in the
      size of ischemic injury after focal ischemia. The tissue-sparing effect of
      ifenprodil is not related to its vasoactive properties. It is likely that its
      neuroprotective effects are related to its ability to antagonize N-methyl-D
      aspartate receptors, which results in a decrease in brain edema and BBB
      permeability.

PMID- 9007873
TI  - History of the Foundation for International Education in Neurological Surgery.
AB  - ALL NEUROSURGEONS RECOGNIZE the worldwide importance of top-level neurosurgical
      technology, education, and treatment. Many, however, may be unaware of the
      formation of a charitable educational foundation, the Foundation for
      International Education in Neurological Surgery, to promote these ideologies and
      concepts. It was founded more than 25 years ago through the auspices of the
      Congress of Neurological Surgeons, supported by all of the national American
      neurosurgical societies. This article provides the background data of the
      formation of the Foundation for International Education in Neurological Surgery
      and will serve as a reminder to all neurosurgeons of the organization's existence
      and its continued global influence on neurosurgery.

PMID- 9007872
TI  - Attenuation of ischemia-reperfusion injury in the rat neocortex by the hydroxyl
      radical scavenger nicaraven.
AB  - OBJECTIVE: Oxygen free radicals are considered important contributors to cerebral
      ischemia-reperfusion injury. The purpose of this study was to examine the effects
      of the hydroxyl radical scavenger, (+/-)-N, N'-propylenedinicotinamide
      (nicaraven), on cerebral injury after focal ischemia-reperfusion. METHODS: A
      total of 58 male Sprague-Dawley rats was subjected to transient focal ischemia by
      occluding both carotid arteries and one middle cerebral artery for 3 hours.
      Animals received continuous infusions of doses of 20 mg/kg per hour or 60 mg/kg
      per hour of nicaraven beginning either 10 minutes before (pretreatment) or
      immediately after (posttreatment) ischemia. Infarction volumes were evaluated by
      staining coronal brain sections with 2% 2,3,5-triphenyltetrazolium chloride (n =
      40). In other animals (n = 18), brain edema was evaluated 1 hour after ischemia.
      RESULTS: A dose of 20 mg/kg per hour of nicaraven elicited small reductions in
      infarction volume (14.7 and 12.3% for the pre- and posttreatment groups,
      respectively). Treatment with a dose of 60 mg/kg per hour of nicaraven provided
      significant reductions in the volume of infarction (18.6% [P < 0.05] and 20.9% [P
      < 0.01] reductions for the pre- and posttreatment groups, respectively). The
      reductions in infarction size did not differ significantly between the pre- and
      posttreatment groups receiving a dose of 60 mg/kg per hour of nicaraven.
      Posttreatment with either dose of nicaraven significantly reduced brain edema.
      CONCLUSIONS: This study demonstrates the neuroprotective effects of a hydroxyl
      radical scavenger when administered systemically during the reperfusion phase
      after transient focal ischemia. The results provide, to our knowledge, the first
      evidence that nicaraven is effective against ischemia-reperfusion injury in the
      brain and demonstrate that oxygen free radicals generated during reperfusion are
      important triggers of ischemic brain damage. Furthermore, the findings suggest
      that nicaraven may be a useful agent in limiting brain injury after ischemic
      stroke.

PMID- 9007874
TI  - Byron Stookey: "the old lion"--an unsung giant of neurosurgery.
AB  - BYRON POLK STOOKEY, an outstanding clinician and teacher, served as Director and
      Chief of Neurosurgery at the Neurological Institute of New York Columbia
      Presbyterian Medical Center. Highlights of his clinical contributions include
      improved peripheral nerve and spine surgery and subtemporal trigeminal nerve
      section for tic douloureux. Through diverse activities in both the political and
      academic arenas of patient care, education, and research, stookey helped to build
      and strengthen neurosurgery between the world wars and helped to prepare the
      foundation for the accomplishments of recent decades.

PMID- 9007875
TI  - Tumors of Heschl's gyrus: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: The clinical presentation and treatment of patients
      with lesions involving Heschl's gyrus is reported. Intraoperative bipolar
      cortical stimulation mapping of Heschl's gyrus has not been previously reported.
      Only monopolar stimulation of this region (with potential electrical recruitment
      of large areas of surrounding cortex) has been undertaken. CLINICAL PRESENTATION:
      Two patients with intrinsic brain tumors located in Heschl's gyrus, in the
      hemisphere dominant for speech, presented with interictal or ictal auditory
      changes. INTERVENTION: Craniotomies were performed with the patients awake and
      with intraoperative bipolar cortical stimulation mapping of language cortex and
      of Heschl's gyrus. CONCLUSION: In contrast to previous studies using monopolar
      cortical stimulation, auditory changes were not elicited by stimulation. In one
      of the patients, a persistent interictal ringing sound stopped abruptly during
      lesion resection. Neither patient had essential temporal lobe language cortex
      near the lesion. Lesions in Heschl's gyrus can be identified by clinical
      presentation and magnetic resonance imaging. Based on topographic anatomy,
      cytoarchitecture, and functional mapping data, these lesions may be resectable
      without language or auditory mapping, although further experience will be
      necessary to confirm this observation.

PMID- 9007876
TI  - Homozygous p53 gene mutation in a radiation-induced glioblastoma 10 years after
      treatment for an intracranial germ cell tumor: case report.
AB  - OBJECTIVE: Radiation-induced glioma is a rare but serious complication of
      radiotherapy. Underlying radiation-induced mutations in oncogenes or tumor
      suppressor genes have not previously been described. CLINICAL PRESENTATION: A 16
      year-old female patient developed a glioblastoma in the right frontal lobe 10
      years after treatment of a suprasellar germ cell tumor with 50 Gy ionizing
      radiation. The glioblastoma was undetectable on a high-resolution magnetic
      resonance image obtained 3 months before diagnosis. METHODS AND RESULTS: A p53
      functional assay was used to examine the transcriptional competence of the p53
      tumor suppressor gene. This assay scores the content of mutant p53 alleles in
      tumor and blood samples quantitatively as a percentage of red yeast colonies. The
      glioblastoma contained 95% mutant p53 alleles, whereas blood from the patient and
      her parents contained only normal background levels of red colonies. Sequencing
      revealed that the mutation in the tumor was a 3-base pair deletion affecting
      codons 238 and 239. Intragenic deletion within the p53 deoxyribonucleic acid
      binding domain is uncommon in sporadic tumors but would be entirely consistent
      with misrepair of a radiation-induced double-strand deoxyribonucleic acid break
      in this case. CONCLUSION: This is the first case in which a causative underlying
      genetic event has been identified in a radiation-induced glioblastoma. We infer
      that mutation of one p53 allele occurred at the time of radiotherapy, and the
      sudden appearance of the tumor 10 years later occurred after loss of the
      remaining wild-type allele and/or other genetic alterations, such as chromosome
      10 loss and epidermal growth factor receptor gene amplification.

PMID- 9007877
TI  - Fenestrated oculomotor nerve caused by internal carotid-posterior communicating
      artery aneurysm: case report.
AB  - OBJECTIVE AND IMPORTANCE: The fenestrated oculomotor nerve associated with the
      internal carotid-posterior communicating artery aneurysm is very rare. CLINICAL
      PRESENTATION: A 48-year-old woman had a history of subarachnoid hemorrhage caused
      by a ruptured right middle cerebral artery aneurysm, which was wrapped with good
      postoperative course. Twenty years later, the patient suffered frontal headache
      with a mild oculomotor nerve paresis in the right side. Follow-up neuroimaging
      studies demonstrated a de novo right internal carotid-posterior communicating
      artery aneurysm. INTERVENTION: The aneurysm was exposed and clipped via a right
      pterional route. The fenestrated oculomotor nerve associated with the aneurysm
      was confirmed at surgery. CONCLUSION: We speculated that the fenestration was
      most likely caused, by the growth of the aneurysm.

PMID- 9007878
TI  - Ruptured distal accessory anterior cerebral artery aneurysm: case report.
AB  - OBJECTIVE AND IMPORTANCE: Accessory anterior cerebral artery (ACA), which is a
      type of median artery of anomalous triplicate ACA, is not rare, but aneurysmal
      formation is extremely rare. We report a rare case with ruptured aneurysm arising
      from a distal accessory ACA. We discuss the characteristics and causes of this
      type of aneurysm and classification of this anomaly. CLINICAL PRESENTATION: A 63
      year-old man suddenly developed severe headache and then loss of consciousness
      and paraplegia. Computed tomography disclosed thick and diffuse subarachnoid
      hemorrhage and interhemispheric hematoma. Subsequent bleeding occurred 2 hours
      after the first hemorrhage. Cerebral angiography disclosed a saccular aneurysm
      arising from the distal accessory ACA. INTERVENTION: Neck clipping of the
      aneurysm was performed 22 hours after the second episode, using an
      interhemispheric approach. CONCLUSION: Although transient paraplegia occurred 8
      days after onset, the patient recovered well after surgery without neurological
      deficit. The characteristics of the aneurysm arising from distal accessory ACA
      are considered similar to those of distal ACA aneurysm. There is, however, some
      confusion regarding the terminology of the anterior communicating artery complex
      anomalies, which we discuss.

PMID- 9007880
TI  - Primary hydatid cyst of sacral spinal canal: case report.
AB  - OBJECTIVE AND IMPORTANCE: Primary hydatid cysts of the spinal canal are very
      rare. The patient in the present case presented with lower cauda equina
      compression caused by a primary solitary hydatid cyst of the sacral spinal canal,
      which is a remote possibility. To the best of our knowledge, such a case has not
      been reported previously. CLINICAL PRESENTATION: A 15-year-old male patient
      presented with lower motor neurone type of bladder and bowel involvement, with
      saddle-shaped anesthesia involving S2-S5 dermatomes. Plain x-rays and magnetic
      resonance imaging (MRI) scans revealed a widened sacral canal with pressure
      changes. MRI scans confirmed the cystic nature of the lesion, which had no
      specific characteristics and demonstrated intensities that were similar to those
      of cerebrospinal fluid. TECHNIQUE: Surgical exploration of the sacral canal with
      enucleation of the cyst in toto was performed. A midline posterior approach was
      used by decompressing thinned posterior elements. Adjuvant therapy with
      mebendazole or albendazole was not administered, although recently, some authors
      claim good results with integrated surgical and medical treatment. CONCLUSION:
      The patient experienced dramatic improvement and became continent. At a follow-up
      examination after 1 year, he had only minimal urinary stress incontinence. If
      spinal hydatid cyst is surgically removed unruptured and other common primary
      sites are excluded, medical treatment can be deferred, provided the patient
      undergoes strict follow-up. MRI, although not specific for hydatid disease,
      should be the investigation of choice in suspected cases of spinal hydatid cyst.

PMID- 9007879
TI  - Pathological consideration of a "blister-like" aneurysm at the superior wall of
      the internal carotid artery: case report.
AB  - OBJECTIVE AND IMPORTANCE: Although the incidence is low, a very small aneurysm
      with a thin wall and no neck arises at the superior wall of the supraclinoid
      portion of the internal carotid artery and is called a "blister-like" aneurysm.
      However, the pathogenesis of such a vascular lesion remains uncertain. CLINICAL
      PRESENTATION: A 57-year-old man developed a fatal subarachnoid hemorrhage caused
      by the rupture of a blister-like aneurysm at the superior wall of the internal
      carotid artery. An autopsy was performed, and the lesion was pathologically
      examined. RESULTS: The internal elastic lamina and media had disappeared at the
      border between the eccentrically sclerotic and normal carotid wall. The gap in
      the internal elastica was covered with normal adventitia and fibrinous tissue.
      This portion was not composed of collagenous tissue as ordinarily seen in an
      aneurysmal wall. Neither infiltration of inflammatory cells nor dissection of the
      artery were observed. CONCLUSION: The blister-like aneurysm appeared to be a
      laceration of the carotid wall based on degeneration of the internal elastic
      lamina.

PMID- 9007881
TI  - Pediatric intracranial hemangioendotheliomas: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intracranial hemangioendotheliomas are rare lesions,
      especially in the pediatric age group. Recognizing hemangioendotheliomas as a
      differential in intracranial tumors of vascular origin is important; complete
      excision results in a cure, and medical therapy for those lesions that are not
      resectable produces long-term survival. CLINICAL PRESENTATION: We report two
      patients, a 7-year-old female patient with a lesion in the right gasserian
      ganglion and a 3-month-old male patient with a cervicomedullary junction tumor.
      INTERVENTION: The 7-year-old underwent a gross total removal with no recurrence.
      The 3-month-old underwent a partial resection followed by treatment with
      interferon alpha-2a, with a decrease in the size of the residual tumor. Both
      patients have been followed for more than 4 years without a recurrence or
      progression of the tumor. CONCLUSION: Hemangioendotheliomas are fairly indolent
      tumors and may be treated with complete surgical resection, resulting in a cure.
      In cases in which complete tumor removal is not possible, adjunctive therapy with
      interferon alpha-2a may control residual tumor growth.

PMID- 9007882
TI  - Management of pilocytic astrocytoma.
AB  - Pilocytic astrocytoma, when totally resected, has a favorable outcome compared to
      other astrocytomas. However, when residual tumor remains, the prognosis is less
      satisfactory. Our study addressed the issues of prognosis in cases of residual
      tumor and the effect of post-surgical radiation therapy on tumor recurrence. We
      analyzed 41 cases of pilocytic astrocytoma which were diagnosed by histologic
      examination. Twenty-six patients were 15 years old or younger, and 15 patients
      were 16 years old or older. An analysis of the relationship between age and tumor
      location revealed a cerebellar predominance in both age groups; however, there
      were more brain stem and basal ganglia tumors among adults. Overall prognosis was
      favorable, with a 2-year survival rate of 97.6%, 94.6% at 5 years, and 94.6% at
      10 years. Children had a better prognosis than adults due to more favorable tumor
      location. Gross total resection resulted in the best prognosis, i.e., no
      recurrence during a 10-year follow-up period. Radiation treatment after surgery
      suppressed residual tumor. We concluded that the best treatment for pilocytic
      astrocytoma is: 1) total resection, if possible, followed by 2) irradiation of
      any residual tumor to suppress recurrence.

PMID- 9007883
TI  - Solitary brain metastases from non-oat cell lung cancer: clinical and prognostic
      features.
AB  - The authors report 91 cases of solitary brain metastasis from non-oat cell lung
      cancer, 66 patients were males and 25 females; average age was 57 years (range 40
      72 years). Surgical removal was total in 80 cases and partial in 11. All patients
      received postoperative radiotherapy and 40 chemotherapy. Histologically, the
      tumor was an adenocarcinoma in 51 cases (56%), a squamous cell carcinoma in 22
      (24%), an undifferentiated carcinoma in 18 (20%). Median survival was 16 months
      and the main cause of death was progression of the primary cancer (59% of cases).
      Survival was influenced by staging of the primary tumor, while no prognostic
      significance was found regarding the type of clinical tumor onset, type of
      radiotherapy and the histotype of the lesion. Use of the "no internal touch"
      technique and brain radiotherapy reduced local brain relapse.

PMID- 9007884
TI  - Analgesic effect of epidural morphine in lumbar disc surgery.
AB  - In patients operated on for herniated lumbar disc, epidural morphine was
      administered intraoperatively at the end of the procedure. A 10 milligram dose of
      morphine provided significant pain relief expressed by less requirement for
      strong analgesics on the day of operation and the day following, as well as for
      sedatives during the postoperative observation period of four days in comparison
      to a control group of patients. The only side effect observed was urinary
      retention.

PMID- 9007885
TI  - Evaluation of regional cerebral blood flow using single photon emission
      tomography for the selection of patients for local fibrinolytic therapy of acute
      cerebral embolism.
AB  - To clarify the indications for local fibrinolytic therapy for acute cerebral
      embolism, correlation among initial regional cerebral blood flow (rCBF)
      abnormalities, recanalization timing, and computed tomographic scan (CT) findings
      two days later were evaluated in 17 cases. All cases included had embolic
      occlusion of middle cerebral or internal carotid arteries which showed no
      abnormal findings on initial CT corresponding to the acute events but did show
      abnormal CBF reduction on initial single photon emission computed tomography
      (SPECT). Relative rCBF was evaluated as the percentage radioisotope counts in the
      region of interest (ROI) of the affected side against the corresponding ROI in
      the unaffected contralateral side. Within 6 hours from onset, there was a
      tendency towards reversed time dependent tolerance of cortical infarction with
      residual relative rCBF. Hemorrhagic transformation was observed in one case whose
      relative rCBF was 35% or less. In 10 patients whose occluded arteries were not
      recanalized within 6 hours, cortical areas with residual relative rCBF of 70% or
      more did not develop infarction. In conclusions, a pre-therapeutic rCBF study
      using SPECT is considered to be mandatory: cases with moderate ischemia involving
      the cortex with residual relative rCBF of between 35% and 70% may be good
      candidates for local fibrinolytic therapy.

PMID- 9007886
TI  - Trigeminal neuralgia related to cerebellopontine angle tumors.
AB  - A review of 30 cases with cerebellopontine angle tumors was carried out to
      identify patients with trigeminal neuralgia (TN) at presentation and to compare
      them with patients without TN. The study shows that dermoid tumors and the
      presence of tumor at the apex of petrous bone on CT are associated with a
      significantly higher incidence of TN, while the incidence did not appear to be
      influenced by age, sex, or size of tumor. In all patients but one (with
      medulloblastoma) that had surgery, there the TN disappeared following total or
      subtotal excision of the tumor, providing the trigeminal nerve was well
      decompressed. Patients with TN should be investigated carefully by CT or MRI
      irrespective of their age or the absence of neurological signs.

PMID- 9007887
TI  - Tumors of the cerebellopontine angle. Changing policy in treatment.
AB  - One hundred and twenty-six cases of cerebellopontine angle tumors with various
      histologies are presented. Results of 75 operated vestibular neurinomas, 22
      meningiomas, and 16 tumors with other histologies are discussed. The method of
      irradiation and non-radical surgery may be an alternative for treatment.

PMID- 9007888
TI  - CNS involvement of Langerhans cell histiocytosis. Report of 23 surgically treated
      cases.
AB  - We present 23 cases of Langerhans cell histiocytosis with central nervous system
      (CNS) involvement. The major complaints were a mass on the cranial vault in
      fifteen (65%), visual disturbance in four (16%), polyurea-polydipsia in three
      (13%), and progressive weakness in all extremities in one patient (4%).
      Neurological examination revealed no abnormality in sixteen patients (70%),
      cranial nerve palsy, visual field defect and optic atrophy in six (26%) and
      paraparesis in one (4%). Tumoral mass was found to be located on the cranial
      vault (65%), in the suprasellar region (21%) and in the spinal column (8%). The
      cranium and spinal column were both involved in one patient. All patients
      underwent surgery; craniectomy with grossly total tumor excision plus
      cranioplasty (65%), craniotomy with subtotal tumor excision (26%), and
      vertebrectomy with grafting (13%) were performed. The clinical, radiological and
      histopathological features, as well as therapeutical considerations are discussed
      and the pertinent literature is reviewed.

PMID- 9007889
TI  - Ultrastructural changes in the blood-brain barrier in rats after treatment with
      nimodipine and flunarizine. A comparison.
AB  - The idea of using induced hypertension to treat the symptomatic ischaemia
      resulting from vasospasm after subarachnoidal hemorrhage, and the effect of this
      therapy on the blood-brain barrier, is checked in animal experiments. This
      therapy is combined with the application of nimodipine, which is recognised as
      the standard medication for prophylaxis of vasospasm. The effects of the induced
      hypertension combination with Nimodipine and in combination with another calcium
      antagonist, Flunarizine are compared. Seventy-four narcotised rats, one group
      with 22 animals treated with Nimodipine and 22 with placebo, and a second group
      20 animals treated with Flunarizine and 10 with placebo, are evaluated. The blood
      pressure is raised to 150-180 mmHg by i.v. application of norfenephrine and
      measured continuously. The standard tracer, horseradish peroxidase, is applied as
      indicator for the blood-brain barrier function. 15 minutes later the experimental
      animals are exsanguinated by perfusion with saline, then perfused with
      Karnovsky's solution. After removal, the brains are stained for peroxidase to
      visualise extravasation of the horseradish peroxidase, and after evaluation of
      the results each brain is assigned to its experimental group. In the Nimodipine
      group, a significant accumulation (p < 0.001) of perivascular deposits of
      peroxidase reaction product were found, these were not found in the placebo
      group. The Flunarizine group does not differ from its placebo group in the number
      of extravasates, and thus, with respect to protein extravasation, appears better
      than the Nimodipine group. In electron micrographs of the extravasates one sees
      intact tight junctions and a neuroendothelial transport, and also vesicles,
      filled with horseradish peroxidase in the endothelium, the muscle cells, and the
      brain parenchyma, which arise from pinocytosis. The vesicles, which transport the
      high-molecular-weight protein, horseradish peroxidase, also transport other
      proteins and can, therefore, cause a brain edema. It follows from these
      morphological results that Nimodipine can disrupt the blood brain barrier
      function and can, therefore, also interfere with cerebral autoregulation, which
      depends on the resistance of vessels.

PMID- 9007890
TI  - Response of cavernous sinus hemangioma to radiotherapy: a case report.
AB  - The author reports a case of a histologically proven cavernous hemangioma of the
      cavernous sinus and middle fossa, which was treated by radiotherapy. This very
      rare lesion represents a formidable challenge to the neurosurgeon and its
      excision has been associated with a considerable mortality rate. The significant
      reduction in the size of tumor of our patient after radiotherapy and the
      corresponding improvement in her clinical condition provide further evidence in
      support of the use of radiotherapy as the first line treatment modality after the
      histological confirmation of a cavernous sinus hemangioma. Surgery should be
      reserved for tumors that fail to respond to radiotherapy or recur after an
      initial good response to radiotherapy.

PMID- 9007891
TI  - Craniopharyngioma extended into the posterior fossa.
AB  - A 7-year-old girl with a craniopharyngioma with a rare extension into the
      posterior fossa is presented. MRI revealed a solid calcified mass in the sellar
      and suprasellar region with a cyst expanded to the posterior fossa up to the
      foramen magnum and causing hydrocephalus and brainstem displacement. The tumor
      was removed totally with right pterional approach.

PMID- 9007892
TI  - Intracerebral schwannoma: case report and review.
AB  - A case of intraparenchymal schwannoma of the brain in a 4-year-old girl is
      presented. Most of the small number of intracranial schwannomas unassociated with
      cranial nerves, reported have occurred in children or young adults. There is no
      male or female predominance. Most of the parenchymatous schwannomas are located
      supratentorially. The presence of a cyst together with the tumor appears to be
      characteristic of intraparenchymal schwannoma of the brain.

PMID- 9007893
TI  - Large intrathoracic meningocele in a patient with neurofibromatosis: technical
      report.
AB  - The authors describe a case of large intrathoracic meningocele (16 cm) associated
      with neurofibromatosis. Computed tomography with metrizamide myelography proved
      valuable in locating the lesion and in reformation after surgery. The authors
      make some comments about surgical excision of large meningocele.

PMID- 9007894
TI  - Hirsutism as a first manifestation of a giant arachnoid cyst of the sylvian
      fissure.
AB  - In this report, we present a case presenting with hirsutism. In this case, there
      was a large sylvian fissure arachnoid cyst demonstrated by radiology. This case
      is discussed in view of clinical findings and a literature review is presented.

PMID- 9007895
TI  - Non-invasive diagnosis of traumatic occlusion of extracranial internal carotid
      artery by magnetic resonance angiography.
AB  - A case of traumatic occlusion of the left extracranial internal carotid artery
      that was diagnosed by magnetic resonance angiography is reported. The non
      invasiveness and safety of drug therapy is superior to intraarterial digital
      angiography.

PMID- 9007896
TI  - Intraparenchymal meningioma: an unusual radiologic and anatomic presentation of a
      meningioma. Case report.
AB  - The authors describe a case of a completely intrinsic brain tumor which was
      resected totally and which proved to be a meningioma. In correlation with this
      anatomic diversity, the MRI findings also significantly differed from that of the
      known radiologic features of classical meningioma.

PMID- 9007897
TI  - Nurse practitioner disagrees with comparison to unlicensed aides.

PMID- 9007898
TI  - Disease management provides a comprehensive approach to managing healthcare
      delivery.

PMID- 9007899
TI  - Nurses can learn to manage the unique side effects and adverse reactions
      associated with docetaxel.

PMID- 9007900
TI  - Patients can manage intraspinal analgesia at home.

PMID- 9007901
TI  - Meat tenderizer unclogs enteral feeding tubes.

PMID- 9007903
TI  - Simple nursing interventions facilitate managing hepatic surgery.

PMID- 9007902
TI  - Nursing assessment and interventions minimize nutritional side effects for
      patients with head and neck cancer.

PMID- 9007904
TI  - Patients require safety education regarding polio vaccine.

PMID- 9007905
TI  - Quality of life and the cancer experience: the state-of-the-knowledge.
AB  - PURPOSE/OBJECTIVES: To address the state-of-the-knowledge concerning quality of
      life (QOL) issues and the cancer experience from theoretical, research, clinical,
      and educational perspectives. DATA SOURCES: Published books and articles and a
      panel of experienced QOL experts who convened at the Oncology Nursing Society's
      State-of-the-knowledge Conference on Quality of Life in February 1995. DATA
      SYNTHESIS: Despite the evolution and support of QOL in oncology nursing practice,
      education, and research, there remains gaps in theory, research, and practice
      related to QOL. This article explores these gaps in knowledge and recommends
      future directions for QOL theory, research, education, and practice. CONCLUSIONS:
      Further conceptual work and resolution of QOL methodologic issues to guide
      clinical practice and education are warranted. The impact of cultural variables
      and precancer life experiences on patients' perceptions of QOL also must be
      addressed. NURSING IMPLICATIONS: Oncology nurse clinicians, educators, and
      researchers must continue to work collaboratively to enhance the knowledge base
      regarding QOL and to improve the nursing care provided to individuals with
      cancer.

PMID- 9007906
TI  - Patients' perspectives of fatigue while undergoing chemotherapy.
AB  - PURPOSE/OBJECTIVES: To explore the experience of fatigue from the perspective of
      patients undergoing chemotherapy. DESIGN: Qualitative research and secondary
      analysis of data from a larger study. SETTING: Participants were recruited from
      18 sites, including large outpatient chemotherapy clinics and private medical
      oncologists' offices. SAMPLE: 127 adult patients who were beginning their first
      protocol of chemotherapy. METHODS: Data were collected through individual and
      open-ended interviews and a qualitative, thematic analysis of the participants'
      responses using grounded theory techniques. MAIN RESEARCH VARIABLE: The
      experience of fatigue as perceived by patients undergoing chemotherapy. FINDINGS:
      The analysis resulted in eight major thematic categories: (a) experiencing
      fatigue, (b) effects on well-being, (c) attribution of origin, (d) awareness and
      expectations, (e) emotional reactions, (f) activity, (g) the "biggest" concern,
      and (h) strategies and plans. CONCLUSIONS: This study demonstrates the variation,
      extent, duration, and temporality of fatigue among patients receiving
      chemotherapy and the dynamic, changing aspects of the experience. IMPLICATIONS
      FOR NURSING PRACTICE: Fatigue must be considered within the context of patients'
      daily lives and environments, disease processes, and treatment modalities. Nurses
      must listen carefully to patients' own descriptions of being tired. Further
      research examining patients' perspectives of and experiences related to fatigue
      is necessary to increase the theoretical understanding of fatigue and to improve
      therapeutic nursing interventions.

PMID- 9007907
TI  - Relieving nausea and vomiting in patients with cancer: a treatment algorithm.
AB  - PURPOSE/OBJECTIVES: To describe a treatment algorithm for the choice of
      antiemetic therapy for the patient receiving chemotherapy. DATA SOURCES:
      Published literature, data collected on an inpatient oncology unit. DATA
      SYNTHESIS: Because little information is available to systematically guide
      clinicians in choosing the best antiemetic for an individual patient who is
      receiving a particular chemotherapy protocol, a treatment algorithm was
      developed. The four main variables include emetogenicity of the protocol,
      patient's age, previous adverse reaction to antiemetics, and failure of previous
      antiemetics. Other factors to consider include alcohol use, anticipatory nausea,
      patient health status, nausea history not related to chemotherapy, and type and
      availability of IV access. CONCLUSION: The use of this algorithm resulted in
      appropriate choice of antiemetics and improved patient outcomes associated with
      reduced incidence of nausea and vomiting. IMPLICATIONS FOR NURSING PRACTICE:
      Nurses can have a significant impact on a patient's experience with chemotherapy
      treatment by improving symptom management of nausea and vomiting.

PMID- 9007908
TI  - Life stress and risk of precancerous cervical lesions: a pretest directed by the
      life stress model.
AB  - PURPOSE/OBJECTIVES: To present the results of a pilot study to pretest
      instruments designed to measure selected variables named in the Life Stress
      Model, a model of health outcomes. Additional aims were to determine the effect
      of completing personal risk assessments for precancerous squamous-cell
      intraepithelial lesions of the cervic (SIL) on receptivity to cervical cancer
      prevention information and to extend knowledge of stressful life events
      experienced by inner-city women attending high-risk health clinics. DESIGN: Cross
      sectional. SAMPLE: 20 adult women attending high-risk prenatal or human
      immunodeficiency virus (HIV) outpatient clinics in one of two New York City
      hospitals. Most were recovering drugs abusers; half were diagnosed with HIV
      infections. METHODS: Data were collected by self-report using standard measures.
      Demographics, medical histories of immunosuppressive states, and investigator
      developed screening inventories of behavioral and dietary risk factors associated
      with SIL also were administered. MAIN RESEARCH VARIABLES: Life event stressors,
      psychological state, social support, symptom distress, and SIL diagnosis.
      FINDINGS: Instruments met acceptable psychometric standards for internal
      consistency, but the standard measure of stressful life events did not capture
      the full range of stressors experienced by this group of patients: hovering
      relatives, abusive spouses, HIV diagnosis, changes in welfare benefits, the HIV
      status of the unborn, and mandatory foster care. Although unable to recall cancer
      histories of family members, about half of the women who completed study
      instruments were interested in receiving more information cervical cancer.
      Exploratory analyses suggest that women diagnosed with SIL experience more
      psychological distress and family disfunction than women without SIL.
      CONCLUSIONS: Completing personal SIL risk assessments may stimulate patients'
      receptivity to cancer risk factor information. Health outcomes studies guided by
      the Life Stress Model may prove fruitful. IMPLICATIONS FOR NURSING PRACTICE:
      Cancer risk factor assessments may be an important method for promoting
      receptivity to cancer prevention information.

PMID- 9007909
TI  - The needs of patients with cancer and their caregivers in rural areas.
AB  - PURPOSE/OBJECTIVES: To describe physical and psychological needs, rank their
      importance, and identify needs that were not met of patients with cancer and
      their caregivers living in rural settings. DESIGN: Exploratory descriptive.
      SETTING: Rural Vermont. SAMPLE: 30 patients with cancer and 30 caregivers.
      METHODS: Patients completed the self-administered. 104-item Patient Needs Scale;
      caregivers completed the self-administered, 90-item Caregiver Needs Scale.
      Respondents were asked to rate the importance of an item on a scale of 1-10 if
      they considered if a need. If a numbered item was scored, respondents identified
      whether the need was met. FINDINGS: The patient group identified 49% of scale
      items as needs; the caregiver group identified 41% of scale items as needs.
      Greater than 50% of the patient and caregiver respondents identified needs in
      areas of personal care. Involvement with health care, and interpersonal
      Interaction as very important. The patient group reported that 5% of identified
      needs were unmet, whereas the caregiver group reported that 14% of identified
      needs were unmet. CONCLUSIONS: In rural settings, caregiver needs, while fewer in
      number, are not met three times more frequently than patient needs. IMPLICATIONS
      FOR NURSING PRACTICE: The needs identified by more than 50% of both groups should
      be included in assessment and care plans. The variability of patient and
      caregiver needs reinforces the importance of individual assessment and planning
      rather than making assumptions about needs. Future research may include
      identifying questions to elicit current needs and determining how often these
      questions should be asked to meet changing needs.

PMID- 9007910
TI  - Dihydropyrimidine dehydrogenase deficiency: a pharmacogenetic defect causing
      severe adverse reactions to 5-fluorouracil-based chemotherapy.
AB  - PURPOSE/OBJECTIVES: To describe the pharmacogenetic syndrome of dihydropyrimidine
      dehydrogenase (DPD) deficiency, which predisposes patients with cancer to
      potentially lethal adverse reactions following 5-fluorouracil (5-FU)-based
      chemotherapy. DATA SOURCES: Published articles, abstracts, and conference
      proceedings. DATA SYNTHESIS: Genetic deficiencies in DPD, the rate-limiting
      enzyme responsible for 5-FU catabolism, may occur in 3% or more of patients with
      cancer putting them at increased risk for unusually severe adverse reactions
      (e.g., diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity) to
      standard doses of 5-FU. Diagnosis of DPD deficiency must be confirmed by
      specialized laboratory tests. The principle treatment for DPD-deficient patients
      with severe acute 5-FU reactions is supportive care; however, the administration
      of thymidine potentially may reverse severe 5-FU-induced neurologic symptoms such
      as encephalopathy and coma. CONCLUSIONS: Early recognition of this serious
      pharmacogenetic syndrome may allow for the modification of future chemotherapy,
      thus avoiding further life-threatening toxicities. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses must understand the pharmacology, mechanism of action, clinical
      presentation, potentially lethal risks, and traumatic psychosocial stresses
      experienced by DPD-deficient patients with cancer receiving 5-FU therapy in order
      to develop timely interventions and alternative plans of care.

PMID- 9007911
TI  - Increasing prostate cancer awareness in African American men.
AB  - PURPOSE/OBJECTIVES: To describe the knowledge base of African American men
      regarding prostate cancer and evaluate the immediate effects of an educational
      intervention on short-term knowledge acquisition. DESIGN: Prospective one group
      pretest/post-test. SETTING: Church meetings, Salvation Army senior meetings,
      health fairs, and senior citizens' meetings in the African American community of
      a large midwestern city. SAMPLE: Convenience sample of 75 African American men
      (ages 23-88) who completed a pre- and postintervention questionnaire regarding
      knowledge and awareness of prostate cancer. METHOD: The questionnaire was based
      on patient education material from the American Cancer Society. The instrument
      consisted of seven statements related to prostate cancer incidence, risk factors,
      and detection. Following completion of the preintervention questionnaire, the
      investigator provided subjects with information on prostate cancer. Subjects were
      retested. MAIN RESEARCH VARIABLES: Knowledge and awareness of prostate cancer
      including incidence, risk factors, and detection in African American men.
      FINDINGS: Correct responses increased from 23% (preeducation) to 64%
      (posteducation). The three most frequently missed questions on the pretest
      related to urinary frequency as an early sign of prostate cancer incidence of
      prostate cancer in African American men, and increased risk among African
      American men for prostate cancer when compared to Caucasian men. These items
      remained the three most frequently missed questions on the post-test.
      CONCLUSIONS: An educational intervention had a positive effect on short-term
      knowledge and awareness of prostate cancer in African American men. Additional
      research is necessary to assess long-term retention of information and what
      effect, if any, increased knowledge has on health behavior. IMPLICATIONS FOR
      NURSING PRACTICE: Continued efforts are warranted to encourage this high-risk
      group to participate in prostate screenings. To influence health behavior,
      patient education and information regarding the incidence and mortality of
      prostate cancer is critical in this high-risk population.

PMID- 9007912
TI  - FDA clears new treatment for invasive aspergillosis.

PMID- 9007913
TI  - Muscle contraction and disk displacement.

PMID- 9007915
TI  - Diagnosis of blunt carotid injury in patients with facial trauma.
AB  - OBJECTIVES: The purpose of this study was to review the clinical and diagnostic
      findings associated with blunt carotid artery injury, provide information related
      to clinical outcome, and report the findings of a retrospective study comparing
      patients with nonpenetrating and penetrating carotid artery injuries and the
      attendant facial injuries. STUDY DESIGN: Twenty-one patients admitted to the
      hospital nonelectively with a subsequent diagnosis of penetrating (11 patients)
      or nonpenetrating (10 patients) carotid artery injuries were included in the
      study. Records were analyzed for demographic data, mechanism of injury and time
      to diagnosis, neurologic status, presence of facial injuries, and outcome.
      RESULTS: Five patients had facial injuries associated with a blunt carotid artery
      abnormality; six patients had penetrating carotid wounds. Time from carotid
      injury by all mechanisms to diagnosis was 20 minutes to 12 hours (mean 4 hours).
      Seventeen patients survived their injury. CONCLUSION: Patients with completely
      asymptomatic head injuries and severe closed-head injuries must be given careful
      initial evaluation and subsequent secondary evaluation. The relatively high
      frequency of facial injuries associated with blunt carotid injury should alert
      the maxillofacial surgeon to consider the diagnosis.

PMID- 9007914
TI  - Tomography for temporomandibular disorders.

PMID- 9007916
TI  - Carotid body tumor with concurrent masticatory pain dysfunction.
AB  - The serendipitous finding of a mass in the left neck unrelated to the prior
      masticatory muscle findings brought about prompt angiographic and magnetic
      resonance imaging studies that confirmed the presence of a carotid body tumor.
      The presence of an unrelated pathologic entity in the area from which prior
      complaints and findings had originated can be overlooked if one continues to
      focus on the initial presenting findings. When a more serious and even life
      threatening element emerges during the time of painful dysfunction it may be
      masked by the ongoing symptoms and signs. Failure to recognize the presence of a
      new component with presenting symptoms similar to those ascribed to myofascial
      pain dysfunction is fraught with serious consequences for the patient.

PMID- 9007917
TI  - Clinical evaluation of the use of low-intensity ultrasound in the treatment of
      recurrent aphthous stomatitis.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy of low-intensity
      ultrasound in the treatment of recurrent aphthous stomatitis. STUDY DESIGN: Fifty
      patients with recurrent aphthous stomatitis were enrolled, and 35 patients
      completed this randomized crossover trial. The ultrasound was self-administered
      by twice daily use of an ultrasonic toothbrush. The level of aphthous ulcer
      activity was first observed for each patient with the use of either an ultrasonic
      or placebo toothbrush over a 6 month period. Patients were then observed for a 2
      to 4 month period while using the alternate toothbrush. The level of ulcer
      activity was calculated as a numeric index: the total duration of sores divided
      by the period of observation. Statistical analysis was performed with the
      Student's t test. RESULTS: During the initial study period, the level of aphthous
      ulcer activity was lower for patients in the ultrasonic toothbrush group than for
      those in the placebo group (0.58 versus 0.78). This difference was not
      statistically significant. However, when the patients who used the placebo
      switched to the ultrasonic toothbrush, the level of aphthous ulcer activity
      dropped by 46% (O.81 to 0.44; p < 0.05). Those patients who started with the
      ultrasonic toothbrush worsened slightly after switching to the placebo.
      CONCLUSION: Routine use of low intensity ultrasound appears to have a modest
      beneficial effect on recurrent aphthous stomatitis.

PMID- 9007918
TI  - Efficacy of topical retinoic acid compared with topical fluocinolone acetonide in
      the treatment of oral lichen planus.
AB  - The purpose of this study was to compare the efficacy of retinoic acid in an oral
      base 0.05% with fluocinolone acetonide in an oral base 0.1% in the treatment of
      atrophic and erosive oral lichen planus. Thirty-three patients with
      histologically proven oral lichen planus were asked to participate in the study.
      Lesions were scored ranging from 0 (no lesion) to 5 (large erosion) according to
      the severity. Patients were randomly assigned to receive either topical
      fluocinolone acetonide or topical retinoic acid. They were instructed to apply
      the medication on dried lesions four times a day. The lesions were evaluated
      after 2 and 4 weeks of treatment. The sign scores were analyzed by the Wilcoxon
      rank sum test. Eighteen patients receiving topical fluocinolone acetonide
      improved from the average score of 3.0 to 1.5 after 4 weeks of treatment, whereas
      15 patients receiving topical retinoic acid showed little change (average score,
      2.9 and 2.4, respectively). The changes were statistically significantly
      different between the two groups (p = 0.01). The results suggest that 0.1%
      fluocinolone acetonide reduced the severity of atrophic and erosive oral lichen
      planus better than 0.05% retinoic acid.

PMID- 9007919
TI  - Atypical cartilage in reactive osteocartilagenous metaplasia of the traumatized
      edentulous mandibular ridge.
AB  - Eighteen cases of reactive osteocartilagenous metaplasia of the edentulous
      mandibular alveolar ridge forming clinical masses that mimic neoplasms are
      reported. Although most of these lesions appeared histologically benign, three
      exhibited atypical microscopic features suggestive of chondrosarcoma. Of those
      cases that were followed, none of the lesions recurred after simple surgical
      excision. Because many investigators consider all cartilagenous lesions of the
      jaws potentially malignant, the importance of recognizing this benign condition
      is stressed.

PMID- 9007920
TI  - Anesthetic efficacy of the intraosseous injection of 2% lidocaine (1:100,000
      epinephrine) and 3% mepivacaine in mandibular first molars.
AB  - OBJECTIVES: This study compared the anesthetic efficacy of a primary intraosseous
      injection of 2% lidocaine with 1:100,000 epinephrine and 3% mepivacaine in human
      mandibular first molars. Injection pain and healing postoperatively were also
      assessed for the intraosseous injection. STUDY DESIGN: With the use of a repeated
      measures design, 42 subjects randomly received intraosseous injections of 1.8 ml
      of 2% lidocaine with 1:100,000 epinephrine or 1.8 ml of 3% mepivacaine in a
      double-blind manner at two successive appointments. The first molar and adjacent
      teeth were blindly tested with an electric pulp tester at 2-minute cycles for 60
      minutes. Anesthetic success was defined as no subject response to the maximum
      output of the pulp tester (80 reading) for two consecutive readings. RESULTS:
      Anesthetic success occurred in 74% of the first molars with 2% lidocaine with
      1:100,000 epinephrine and in 45% with 3% mepivacaine. The difference was
      statistically significant (p < 0.05). Overall, onset was rapid for the
      intraosseous injections, the duration of pulpal anesthesia steadily declined over
      the 60 minutes, the majority of the subjects had no pain or mild pain with
      perforation and solution deposition, and 5% of the subjects had delayed healing
      at the perforation sites. CONCLUSIONS: The results of this study indicate that
      the primary intraosseous injection of 2% lidocaine with 1:100,000 epinephrine is
      more successful and results in a longer duration of pulpal anesthesia as compared
      with 3% mepivacaine in noninflamed mandibular first molars. Most subjects
      reported no or mild pain during perforation and injection.

PMID- 9007921
TI  - Intrapulpal injection: factors related to effectiveness.
AB  - The intrapulpal injection is commonly used when conventional anesthetic
      techniques fail during endodontic procedures. OBJECTIVES: This was a double-blind
      clinical study conducted to determine whether anesthetic solution was related to
      an effective intrapulpal injection. STUDY DESIGN: Thirty-five intrapulpal
      injections were given, all with back-pressure and either saline solution or
      anesthetic (2% lidocaine with 1:100,000 epinephrine). RESULTS: Thirty-three of
      the 35 injections were effective. Statistical analysis showed no significant
      difference between the two solutions. CONCLUSIONS: Data indicate that an
      effective intrapulpal injection depends on back-pressure and is independent of
      the solution used.

PMID- 9007923
TI  - National Institutes of Health Technology Assessment Conference on Management of
      Temporomandibular Disorders. Bethesda, Maryland, April 29-May 1, 1996.
      Proceedings.

PMID- 9007922
TI  - Dosimetry and cost of imaging osseointegrated implants with film-based and
      computed tomography.
AB  - Thermoluminescent dosimeters were used to measure radiation doses at craniofacial
      sites in a tissue-equivalent phantom during film-based multidirectional
      tomography with the Tomax Ultrascan (Incubation Industries, Ivyland, Pa.) and
      during computed tomography with the Elscint Excel 2400 (Elscint Corp., Tel Aviv,
      Israel). Mean absorbed doses for presurgical mandibular and maxillary canine and
      molar implant assessments were converted to equivalent doses, which were then
      multiplied by published weighting factors and summed to give effective doses. The
      computed tomography device consistently delivered higher doses than the Tomax
      Ultrascan to all anatomic locations; the differences were most pronounced when
      only one or two implant sites were evaluated. The reasons for the dose
      disparities are considered both anatomically and procedurally. A survey of
      examination cost revealed film-based multidirectional tomography to be less
      expensive than computed tomography.

PMID- 9007924
TI  - History and evolution of TMD concepts.
AB  - Historically the field of temporomandibular disorders (TMD) has been based on
      testimonials, clinical opinion, and blind faith rather than on science.
      Reparative procedures to the joints, jaws, or occlusal surfaces of the teeth to
      develop idealized structural relationships that may be required for dental health
      and function are less likely to be required for the management of chronic
      musculoskeletal disorders. Because of the concerns of many people today regarding
      professional credibility and intellectual honesty, the need for a scientific
      foundation to support the various belief systems is of paramount importance. In
      fact, therapeutic approaches for TMD are undergoing a major evolution away from
      the traditional mechanistic dental concepts of the past to the more current
      biopsychosocial medical concepts that emphasize multidisciplinary approaches.
      Recent advances in the understanding of pain mechanisms and management of chronic
      pain have improved long-term treatment outcome. The emphasis is on treatment that
      involves the patient in the physical and behavioral management of their own
      problem. The majority of patients with TMD achieve good relief of their symptoms
      with noninvasive, conservative therapy.

PMID- 9007925
TI  - Current terminology and diagnostic classification schemes.
AB  - This article reviews the current terminology and classification schemes available
      for temporomandibular disorders. The origin of each term is presented, and the
      classification schemes that have been offered for temporomandibular disorders are
      briefly reviewed. Several important classifications are presented in more detail,
      with mention of advantages and disadvantages. Final recommendations are provided
      for future direction in the area of classification schemes.

PMID- 9007926
TI  - Psychosocial and behavioral assessment of patients with temporomandibular
      disorders: diagnostic and treatment implications.
AB  - The literature on chronic pain reveals that several psychosocial and behavioral
      factors, in addition to physical pathology, play a role in reports of pain and
      disability. Therefore it is important to assess patients more broadly rather than
      focus exclusively on physical pathology. Understanding and treatment of
      temporomandibular disorders has been impeded by the lack of agreement on a
      classification system with which to make a differential diagnosis. Research
      supports the appropriateness of a dual-diagnostic approach for temporomandibular
      disorders based on physical and psychological axes. Treatment should be directed
      toward the physical diagnoses supplemented by treatment that targets relevant
      psychosocial characteristics. This approach encourages diagnosticians to think in
      terms of the two relevant axes and to customize treatment to physical and
      psychosocial characteristics and thus should foster better outcomes.

PMID- 9007927
TI  - Epidemiology and natural progression of articular temporomandibular disorders.
AB  - The reported prevalence of temporomandibular disorders (TMDs) differs from study
      to study, probably because of methodologic errors and lack of standardized
      definitions of TMDs and their characteristics. Classification of TMDs should be
      in accordance with classification of synovial joint disorders as generally used
      by rheumatologists and orthopedic surgeons, in which articular disorders are
      distinguished from nonarticular disorders. Articular temporomandibular disorders
      appear to be self-limiting in a very high percentage of cases. Because of this
      nonprogressive nature, the outcome of nonsurgical management will be highly
      successful.

PMID- 9007928
TI  - Phenomenology, epidemiology, and natural progression of the muscular
      temporomandibular disorders.

PMID- 9007929
TI  - Assessment of physical and behavioral outcomes of treatment.
AB  - This article reviews the availability of reliable and valid measures for
      assessing treatment outcomes and discusses issues related to research design,
      with the goal of identifying design elements that enhance the quality of evidence
      produced by clinical studies of therapeutic interventions. Assessment of outcomes
      in temporomandibular disorders can draw on methods and measures used with other
      chronic or recurrent pain conditions as well as temporomandibular disorder
      specific measures. Reliable outcome measures are available for assessing the
      following: clinical signs and symptoms of temporomandibular disorders; pain
      intensity; affective aspects of pain; pain-related coping; pain behaviors,
      including expressive behaviors, activity limitation and use of health services;
      as well as pain-related disability and life interference. Well-designed measures
      of self-efficacy for controlling pain, explanatory models of pain, and patient
      satisfaction with treatment outcomes are needed. Elements of research design
      necessary for proving the worth of a clinical intervention include randomization,
      blinding, control, low loss to follow up, and an adequate follow-up period.

PMID- 9007930
TI  - The role of occlusal adjustment in the management of temporomandibular disorders.
AB  - The use of occlusal adjustment as a treatment for temporomandibular disorders has
      been questioned because of lack of evidence that occlusal factors play an
      etiologic role; lack of evidence that this irreversible treatment modality has
      sufficient efficacy, when reversible modalities are available; the self-limiting
      character of the disorders; and the possibility of adverse effects. However,
      controlled clinical trials have yielded results that are difficult to explain
      unless occlusal factors have a causal role in temporomandibular disorders.
      Controlled clinical trials also suggest an effect for occlusal adjustment on
      chronic headaches and on chronic neck and shoulder pain in comparison with
      conventional treatments. Moreover, no adverse effects of properly conducted
      occlusal adjustments have been reported. In view of the possibility that occlusal
      factors have a causal role in temporomandibular disorders, research efforts on
      the role of occlusion should be intensified, and teaching should be revised
      accordingly.

PMID- 9007931
TI  - The role of bioelectronic instrumentation in the documentation and management of
      temporomandibular disorders.
AB  - Temporomandibular disorders (TMDs) can affect the form and function of the
      temporomandibular joint, masticatory muscles, and dental apparatus. Electronic
      measurement of mandibular movement and masticatory muscle function provides
      objective data that are defined by commonly accepted parameters in patients with
      TMDs; these data can then be used to design and monitor therapy and enhance
      treatment therapy. In this study, data on 3681 patients with TMD are presented,
      including electronic test data on 1182 treated patients with TMDs. Electronic jaw
      tracking was used to record mandibular movement and to compare the presenting and
      therapeutic dental occlusal positions. Electromyography was used to analyze the
      resting status of masticatory muscles and occlusal function at presentation and
      after therapeutic intervention. Transcutaneous electrical nerve stimulation
      therapy relaxed masticatory muscles and aided in the determination of a
      therapeutic occlusal position. The data show a positive correlation between the
      clinical symptoms of TMD and the presenting occlusion, accompanied by muscle
      activity. A strong positive correlation also appears to exist between a
      therapeutic change in the dental occlusion to a neuromuscularly healthy position
      with use of a precision orthotic appliance and the significant relief of symptoms
      within 1 month and at 3 months.

PMID- 9007932
TI  - The validity and utility of disease detection methods and of occlusal therapy for
      temporomandibular disorders.
AB  - Our evaluation of the clinical usefulness or devices for the diagnosis or
      treatment of temporomandibular disorders (TMD) led to the conclusion that the
      only current gold standard for TMD is a global clinical examination, because none
      of the instruments can be said to provide more than ancillary documentation and
      none have proven diagnostic validity or utility. Regarding the therapeutic
      efficacy of occlusal adjustment, we could find no comparative studies that test
      the efficacy of occlusal adjustment in preventing TMD. The studies we reviewed on
      the relationship of occlusion to TMD are not convincing, powerful, or practical
      enough to make any recommendations about a causal association.

PMID- 9007933
TI  - Orthodontic treatment and temporomandibular disorders.
AB  - The relationship between orthodontic treatment and temporomandibular disorders
      (TMDs) has long been of interest to the practicing orthodontist, but only during
      the past decade have a significant number of clinical studies been conducted that
      have investigated this association. This interest in orthodontics and TMD in part
      was prompted in the late 1980s after litigation that alleged that orthodontic
      treatment was the proximal cause of TMD in orthodontic patients. This litigious
      climate resulted in an increased understanding of the need for risk management as
      well as for methodologically sound clinical studies. The findings of current
      research investigating the relation of orthodontic treatment and TMD can be
      summarized as follows: (1) signs and symptoms of TMD may occur in healthy
      persons; (2) signs and symptoms of TMD increase with age, particularly during
      adolescence, until menopause, and therefore TMDs that originate during
      orthodontic treatment may not be related to the treatment; (3) in general,
      orthodontic treatment performed during adolescence does not increase or decrease
      the chances of development of TMD later in life; (4) the extraction of teeth as
      part of an orthodontic treatment plan does not increase the risk of TMD; (5)
      there is no increased risk of TMD associated with any particular type of
      orthodontic mechanics; (6) although a stable occlusion is a reasonable
      orthodontic treatment goal, not achieving a specific gnathologic ideal occlusion
      does not result in signs and symptoms of TMD; and (7) thus far, there is little
      evidence that orthodontic treatment prevents TMD, although the role of unilateral
      posterior crossbite correction in children may warrant further investigation.

PMID- 9007934
TI  - Physical medicine modalities and trigger point injections in the management of
      temporomandibular disorders and assessing treatment outcome.
AB  - Temporomandibular disorders (TMDs) are principally musculoskeletal, orthopedic,
      and neurologic in nature. The use of trigger point injections and physical
      medicine modalities has become commonplace in the management of TMDs. These
      modalities have a long and successful history in the management of similar
      disorders in other areas of the body, and it is only natural that they would be
      included in the management of TMD as well.

PMID- 9007935
TI  - Physical therapy: a critique.
AB  - Some forms of physical therapy are used relatively frequently in the treatment of
      chronic musculoskeletal pain conditions, including the temporomandibular
      disorders. We found evidence that cold seems to be a useful treatment for
      postsurgical pain and swelling and that most patients being treated for most
      chronic musculoskeletal pain seem to do better with most forms of therapy.
      However, we agree with the authors of previous reviews that there is little
      evidence that these methods of management cause long-lasting reductions in signs
      and symptoms. Findings of recent clinical trials tend to support this conclusion,
      although evidence is beginning to accumulate that exercise programs designed to
      improve physical fitness have beneficial effects on chronic pain and disability
      of the musculoskeletal system.

PMID- 9007936
TI  - Behavioral and educational modalities.
AB  - General agreement has emerged in the scientific literature that behavioral and
      educational modalities are useful and effective in the management of chronic pain
      conditions. Behavioral and educational treatment modalities constitute a
      component of virtually every established chronic pain treatment program. It has
      been demonstrated that management of temporomandibular disorders has benefited
      from such behavioral interventions as well. The label "biobehavioral" refers to
      proven, safe methods that emphasize self-management and acquisition of self
      control over not only pain symptoms but also their cognitive attributions or
      meanings and maintaining a productive level of psychosocial function, even if
      pain is not totally absent. A large collection of treatment modalities is
      subsumed under the label of biobehavioral treatments; the most commonly studied
      of these include biofeedback, stress management, relaxation, hypnosis, and
      education. An NIH Technology and Assessment Conference held in 1995 comprises the
      best available summary of the state of the art concerning the suitability of
      biobehavioral methods as useful approaches to ameliorate chronic pain, including
      TMD. Educational methods have also been demonstrated to be efficacious in the
      self-management of headache and back pain, but only limited data are available
      for TMD. By and large, when biobehavioral treatments are used in the management
      of TMD, effects are virtually always positive and in the hypothesized beneficial
      direction. While effects are often moderate in size, these methods show the
      potential for producing long-lasting benefits when compared with usual clinical
      treatment for TMD. Research has as yet failed to establish one biobehavioral
      modality as superior to another. It is important to note that much the same
      situation is present with regard to the scientifically established validity of
      many biomedically based TMD treatments.

PMID- 9007937
TI  - Pharmacologic treatments for temporomandibular disorders.
AB  - Drugs are widely used in the management of acute and chronic orofacial pain.
      Whereas the use of analgesics for acute orofacial pain is well documented through
      hundreds of controlled clinical trials, the use of a broad spectrum of drugs for
      chronic pain is based on very few studies. In the absence of data supporting a
      therapeutic benefit for a drug used chronically for pain, toxicity associated
      with the drug can still occur. It is critical, therefore, to assess the balance
      between therapeutic benefit and safety. This article reviews current evidence
      supporting the use of several drug classes for temporomandibular disorders (TMD)
      and identifies therapeutic controversies in need of further research.

PMID- 9007938
TI  - Temporomandibular joint devices: treatment factors and outcomes.
AB  - TMJ devices have been used for many years in reconstruction of the
      temporomandibular joint (TMJ). The most common endosseous implant currently used
      in TMJ reconstruction is a mini-anchor that is placed in the posterior head of
      the condyle to support artificial ligaments to stabilize the articular disk in
      the proper position. A 2-year follow-up study shows a success rate of 90% in
      reference to incisal opening jaw and occlusal stability, and significant
      reduction in presurgical pain level. Some materials that have been used in TMJ
      reconstruction, including Proplast-Teflon (PT) and Silastic devices, have caused
      devastating problems for patients. These materials, (particularly the PT) can
      cause severe foreign-body giant-cell reaction, severe bone and soft-tissue
      destruction, and migration of particles to other body areas, and may initiate or
      exacerbate connective tissue and autoimmune disease problems. Christensen joint
      prosthesis has been reported to have very good success in TMJ reconstruction. The
      most thoroughly studied TMJ total joint device is the Techmedica custom-made
      total joint prosthesis, with a 5-year follow-up study on 31 patients and 52
      reconstructed joints. All patients have functioning prostheses with good jaw and
      occlusal stability and an average pain reduction of 4.4 points on a 0-to-10
      visual analog pain scale. However, this device currently is unavailable. In
      complex cases requiring multiple TMJ operations, particularly those with
      previously failed alloplast, a custom-made total joint prosthesis, using
      materials with proven safety and efficacy in orthopedic joint reconstruction, may
      be the only option available to improve predictably the quality of life of these
      patients.

PMID- 9007939
TI  - The role of temporomandibular joint surgery in the treatment of patients with
      internal derangement.
AB  - Surgery of the temporomandibular joint (TMJ) has made considerable progress,
      although significant failures have plagued this field in recent years. Despite
      the controversies, surgery of the TMJ continues to have a small but important
      role in the management of specific temporomandibular disorders. This article
      presents an overview of TMJ surgery. It is concluded that careful case selection
      is the most important aspect for a successful outcome.

PMID- 9007940
TI  - Failed implants and multiple operations.

PMID- 9007941
TI  - The role of arthroscopy in the management of temporomandibular disorders.

PMID- 9007942
TI  - A scientific basis for the biologic regeneration of synovial joints.
AB  - Temporomandibular joint disorders represent a large group of conditions involving
      a local or more generalized musculoskeletal disease process. The disorders have
      many features and many causes and may result in limited or more severe damage of
      the joint associated tissues including the disks, the articular surface, the
      underlying bone, and the ligamentous structures. As our understanding of the
      molecular processes guiding skeletal tissue formation progresses, new
      opportunities arise in the field of skeletal tissue and joint repair.
      Reconstruction of the temporomandibular joint by means of scientifically designed
      approaches will revolutionize surgical treatment modalities.

PMID- 9007943
TI  - Future directions in the treatment of chronic musculoskeletal facial pain: the
      role of evidence-based care.
AB  - Evidence-based care, using principles of clinical epidemiology, promises to alter
      the treatment of chronic musculoskeletal facial pain. With use of a set of "rules
      of evidence," research studies may be rigorously evaluated. Clinicians can master
      this methodology, which may usher in a paradigm shift in clinical care.

PMID- 9007944
TI  - Non-primary cervical adenocarcinomas.
AB  - We reviewed 16 non-primary cervical adenocarcinomas collected during a six year
      period. Ten tumors originated in the endometrium, three in the ovary and one each
      in the bladder, colon and fallopian tube. Tumor spread was identified by combined
      lymphovascular involvement and stromal invasion in five of the 16 cervices,
      lymphovascular involvement alone in four cervices, stromal invasion alone in two
      cervices, lymphovascular involvement with stromal invasion and cervical
      implantation in two cervices and cervical implantation alone in three cervices.
      The three tumors with surface implantation alone were of endometrial origin, had
      minimal if any myometrial invasion, no extrauterine metastases and two had
      malignant peritoneal washings. Of the 13 tumors with cervical lymphovascular
      involvement and/or stromal metastases, 11 had ovarian, nodal and/or peritoneal
      metastases. We conclude that cervical implantation occurs exclusively with
      endometrial adenocarcinomas, that it follows previous cervical instrumentation
      and that the prognosis is dependent on the histoprognostic features of the
      primary endometrial tumor. In contrast, cervical lymphovascular involvement
      and/or stromal metastases usually reflects disseminated pelvic or abdominal
      malignancy with a poor prognosis. However histological examination may not afford
      separation of these two lesions if local cervical invasion is advanced, if spread
      has occurred by more than one mode or if insufficient clinical/surgical
      information is provided.

PMID- 9007945
TI  - Sarcomatoid carcinomas: pathological and histopathogenetic considerations.
AB  - Malignant tumors with a mixed phenotype are a controversial field of pathology.
      In this article the morphological aspects and the immunohistological
      characterization of sarcomatoid carcinomas are presented. These uncommon
      neoplasms show both carcinomatous and sarcomatous features, and have been
      described in the past under a variety of different names causing great
      uncertainty about their classification and histogenesis. They can occur in
      various anatomical sites and exhibit a wide range of microscopic appearances, but
      some features are quite characteristic and are found in many cases. Morphological
      "transition" between carcinomatous and sarcomatous tissue, and detection of
      epithelial characteristics by electron microscopy or immunohistochemistry in the
      sarcomatous component, are very peculiar features of these neoplasms, providing
      both helpful clues for pathological diagnosis and important insights into
      histogenesis. Here a unifying histopathogenetic mechanism based on the phenotypic
      conversion of carcinoma into sarcomatoid tissue is proposed and supporting
      literature data from both experimental systems and clinicopathological
      observations are reviewed and discussed.

PMID- 9007946
TI  - p53 expression in uveal malignant melanomas.
AB  - Mutation of the p53 gene which is located on chromosome 17p is the single most
      frequent alteration observed in human cancer. In this study we evaluate malignant
      melanoma, the most common intraocular neoplasm in adults, for aberrant p53
      expression. Twenty enucleation specimens representing one ciliary body and 17
      choroidal melanomas and two choroidal nevi were studied by immunohistochemistry
      utilizing the D07 anti-p53 antibody and the MIB-1 monoclonal antibody. The tumors
      included two spindle cell and 16 mixed cell (spindle + epithelioid cell)
      melanomas and two spindle cell nevi. The MIB-1 labelling index ranged from < 1%
      (two cases), 1-5% (13 cases) and > 5% (five cases). Of the 18 melanomas, 13 cases
      showed nuclear p53 staining with the p53 index < 1% (two cases), 1-3% (eight
      cases) and 4-5% (three cases). No p53 staining was observed in two malignant
      melanomas of the spindle cell type and in two choroidal nevi. In the 13 malignant
      melanomas of the mixed cell type, there was no correlation between MIB-1 index
      and p53 immunoreactivity. Immunopositivity was not found in normal choroidal
      melanocytes. Our study suggests that p53 alterations may be found in uveal
      melanomas; in our series, p53 positivity was present only in malignant melanomas
      of the mixed cell type.

PMID- 9007947
TI  - Is it Sertoli cell only syndrome? A case study and clinical caution.
AB  - The use of the terminology Sertoli Cell Only Syndrome should be confined to its
      classic definition (ie; total absence of germinal cells) when reporting the
      results of a testicular biopsy, since with intracytoplasmic sperm microinjection
      (ICSI) the presence of any mature sperm in a histological section may mean that
      the patient has a chance of using his own gametes for attempted pregnancy.

PMID- 9007948
TI  - Problems in the histological assessment of hydatidiform moles: a study on
      consensus diagnosis and ploidy status by fluorescent in situ hybridisation.
AB  - Hydropic villi in products of conception continue to pose a diagnostic problem
      for the anatomical pathologist. It is important to distinguish between complete
      hydatidiform mole (CM), partial hydatidiform mole (PM) and hydropic degeneration
      (HD), as hydatidiform moles (especially CM) have a tendency to develop persistent
      trophoblastic disease. Several studies have demonstrated interobserver
      variability in the diagnosis of the three conditions, but there have been no
      studies testing the accuracy of the consensus diagnosis of pathologists
      experienced in the field. In this study four anatomical pathologists with
      experience in diagnosing hydatidiform moles selected five cases of HD, seven
      cases of PM and ten cases of CM on the basis of consensus diagnosis using
      established criteria. Ploidy studies were done on these 22 cases using
      fluorescent in situ hybridisation. The 15 cases of HD and CM were diploid,
      confirming the histological diagnosis. However only five of the seven cases of PM
      were triploid, the other two being diploid. Review of these two diploid cases
      showed a mixture of small and large villi with moderate to marked trophoblastic
      proliferation. On the basis of the significant trophoblastic proliferation and
      the DNA information, the two cases were reclassified as early complete moles.
      This study demonstrates that even pathologists experienced in the field have
      difficulty separating PM from CM. The findings suggest that, in the absence of
      DNA information, a lesion with hydropic villi showing moderate to marked
      trophoblastic proliferation should be classified as a complete mole, even if
      there is a mixture of small and large villi. Ploidy studies are an important
      adjunct to histological diagnosis, especially when there is an overlap of
      features.

PMID- 9007949
TI  - Chronic copper toxicosis presenting as liver failure in an Australian child.
AB  - A 20 month old Caucasian male child, after a five week illness, developed liver
      failure which was successfully treated by liver transplantation. The explanted
      liver had a histology identical to that seen in Indian childhood cirrhosis and
      its copper content was increased tenfold. Water used to prepare the child's milk
      feeds came from a bore via copper conduits and at times contained 120 mumol/l of
      copper, eight times the recommended maximum for human consumption. Because non
      Indian cases of Indian childhood cirrhosis associated with excess copper
      ingestion are increasingly being recognised, and as early treatment can restore
      normal liver morphology, we support the use of the previously suggested
      alternative term for this condition, ie; 'copper-associated liver disease in
      childhood'. Measurement of hepatic copper concentrations in all children less
      than six years of age who develop hepatic failure of unknown cause will increase
      its recognition. On diagnosis sources of increased dietary copper should be
      investigated to ensure that younger siblings are not similarly exposed.

PMID- 9007950
TI  - Infiltration by immunocompetent cells in early stage invasive carcinoma of the
      uterine cervix: a prognostic study.
AB  - In various tumor types dentritic cell, infiltration and the presence of tumor
      infiltrating lymphocytes have been associated with an improved clinical outcome.
      In the uterine cervix these immunocompetent cells have been associated with
      improved prognosis in high stage disease. The current study examines the
      significance of stromal and tumor T-lymphocyte infiltration together with S-100
      positive dendritic cell infiltration in a series of 73 women with low stage (FIGO
      1b) invasive squamous and adenosquamous cervical carcinoma. Thirty four percent
      of cases contained S-100 positive dendritic cells. These were under-represented
      in cases showing pelvic recurrence or distant disease (1 of 11 compared to 24 of
      62 free of recurrence, P = 0.05) and over-represented in cases showing
      lymphatic/capillary space involvement (12 of 23 compared to 13 of 46 without
      vascular space invasion, P = 0.05). The women were followed up for an average of
      5.2 years and the five-year survival for women whose tumors contained S-100
      positive dendritic cells was 92% compared to 73% for negative cases (P = 0.04).
      There was a significant association between a low density of tumor infiltrating T
      cells and risk of pelvic lymph node spread and subsequent local or distant
      disease control failure (P = 0.008). A five year survival advantage was seen with
      five or more CD 3 positive tumor infiltrating T-lymphocytes per high power field
      (90%) compared to a lower count (68%) (P = 0.04). A similar advantage could not
      be demonstrated for a high stromal infiltrate of T-cells. As yet neither the
      specific mechanisms that induce these cells to infiltrate some cervical
      carcinomas nor the nature of the immunological injury that the cells co-ordinate
      in tumor tissue are well understood.

PMID- 9007951
TI  - Is the frequency of mitoses and PCNA positive cells in tissues affected by delay
      in fixation? Lessons for accurate tumor grading.
AB  - Using uniform systematic random sampling, we tested whether a drop in mitoses and
      PCNA (proliferation cell nuclear antigen) positive cells following a delay in
      tissue fixation of up to five hours, would be unequivocally discernible at the
      well perfused periphery from 11 aggressive rat adenocarcinomas. No statistically
      significant difference (0.05 < P < 0.10; 95% Cl (-13.3, 1.3)) was found. We
      attributed this finding to the high proliferative heterogeneity of rapidly
      growing solid tumors because: (1) vascular perfusion is heterogeneous as rapidly
      proliferating epithelial tumors tend to outgrow their blood supply; (2) the ratio
      of perfused/ non-perfused tumor volumes may change as a solid tumor grows,
      altering to the same extent the ratio of proliferative vs. non proliferative
      regions in the tumor; and (3) the duration of mitoses is not constant. The
      consequences for accurate tumor grading are discussed.

PMID- 9007952
TI  - The pathology of hanging deaths in Western Australia.
AB  - We present here the results of a prospective study of the pathology of 233
      fatalities due to hanging in Western Australia (WA). The deaths occurred during
      the 5 year period 1988-92. Post mortem examination of these cases was undertaken
      according to a standardised protocol by forensic pathologists of this office.
      Post mortem findings of a further 37 cases examined by medical practitioners in
      rural WA are also reviewed, making a useful comparison. Petechial hemorrhages, as
      a hallmark of asphyxiation, were present in 113 of the 233 cases (48%). An
      observable ligature mark to the skin of the neck was seen in 230 cases (99%).
      Injury to the tissues of the neck was identified in 122 cases (52%), more
      commonly with complete suspension of the body (62%) than incomplete suspension
      (46%). Neck injury was essentially equally prevalent with a slip-knot (58%) or a
      fixed knot (60%). Other fresh injuries besides the neck injury were present on
      the deceased's body in 80 cases (34%). In the 37 non-metropolitan cases, an
      observable ligature mark to the skin of the neck was recorded in 30 (81%).
      Petechial hemorrhages were described in 3 cases (8%). Internal neck injury was
      apparently observed in 10 cases (27%), although precise detail adequately
      identifying the site of injury was given in only 2 cases (5%).

PMID- 9007953
TI  - A novel antithrombin gene mutation: slippage and mispairing as a mechanism of
      genetic disease.
AB  - There is a high degree of genetic heterogeneity underlying antithrombin
      deficiency indicating that a number of genetic mechanisms are responsible for the
      disorder. We report the identification of a five nucleotide (CAGAA) deletion in
      exon 2 of the antithrombin gene that results in a shift in the frame of
      translation of the mRNA and introduces a premature STOP signal in codon 70. The
      deleted nucleotides represent one repeat of a duplicated sequence within codons
      36-39. The deletion may have arisen by slippage and mispairing of the repeated
      sequences at the replication fork during DNA synthesis.

PMID- 9007954
TI  - A survey of heparin monitoring in Australasia.
AB  - Full dose heparin therapy is monitored by a variety of laboratory methods, of
      which the activated partial thromboplastin time (APTT) is the most popular. A
      large number of APTT reagents are currently available, with different
      sensitivities to heparin evident in many. Within the literature it is apparent
      that there is a lack of consensus, and indeed some confusion, regarding the
      therapeutic ranges for the APTT for standard heparin therapy in the treatment of
      venous thromboembolic disease. Accordingly we conducted an Australasian survey to
      evaluate current laboratory and clinical practices in monitoring heparin therapy,
      to determine the extent of variation in the approach and to stimulate the process
      of standardisation of acceptable procedures and methodology. Results of the
      survey demonstrate that currently there is no uniform practice used to establish
      therapeutic ranges for monitoring standard heparin therapy. Furthermore, results
      suggest that current practice may lead to subtherapeutic anticoagulation in many
      laboratories.

PMID- 9007955
TI  - The incidence of viremia and the heterogeneity of hepatitis C virus genotypes
      among blood donors, hemophiliacs and patients with chronic liver disease.
AB  - Hepatitis C Virus (HCV) is the major cause of parentally transmitted non-A, non-B
      hepatitis. We studied the incidence of HCV Viremia in blood donors, hemophiliacs
      and patients with chronic liver disease who are positive for antibodies to HCV,
      and then correlated the HCV genotypes among the three groups. 23 blood donors, 10
      hemophiliacs and 97 patients with chronic liver disease were found to be positive
      for anti-HCV during this study period from June 1993 to December 1993. Only 3
      (13%) blood donors, 6 (60%) hemophiliacs and 71 (73%) patients with chronic liver
      disease were found to be viremic when tested for HCV RNA by reverse transcriptase
      polymerase chain reaction (RT-PCR). The low incidence of viremia among blood
      donors may be due to any one of the following three reasons. 1, the level of
      viremia was below the level of detection. 2, the viremia was intermittent with
      persistent infection. 3, the majority of cases represented resolved infection.
      The HCV genotypes were heterogeneous among the three groups. All the blood donors
      with viremia and 35 (50%) of patients with chronic liver disease, belonged to
      type II (1b). However only one (17%) of the hemophiliacs belonged to type II
      (1b). Studies have shown that the genotype I(1a) is the predominant type in the
      USA and Europe, whereas type II(1b) is more frequent in the Far East. It is also
      suggested that type II (1b) is associated with non-responsiveness to interferon
      therapy. Our hemophiliacs were treated with imported coagulation factors, thus
      they were probably exposed to the genotypes in the west. There was significant
      difference in the incidence of HCV type II (1b) among local blood donors and
      hemophiliacs (P = 0.005). However the difference between the hemophiliacs and the
      patients with chronic liver disease was not statistically significant. The number
      of patients in this study was too small to draw any firm conclusions. However the
      findings highlight the importance of studying the genotypes of patients with
      Hepatitis C infection due to their relevance in the management of these cases
      with interferon therapy.

PMID- 9007956
TI  - In vitro activity of meropenem compared to nine other antimicrobial agents:
      importance of its stability when used in agar dilution systems.
AB  - The antibacterial activity of meropenem was tested against 426 clinical isolates
      representing a wide range of aerobic and anaerobic species. The in vitro activity
      of meropenem was compared with that of iminpenem, ceftazidime, cefotaxime,
      ciprofloxacin, piperacillin and tobramycin against aerobic isolates, and also
      compared with that of imipenem, metronidazole, cefoxitin, clindamycin and
      piperacillin against the anaerobic isolates. Meropenem exhibited an extended
      spectrum of activity with low minimal inhibitory concentrations (MIC) against
      Gram negative aerobes, anaerobes, Gram positive anaerobes and most of the Gram
      positive aerobes. The MIC90 of meropenem against the Enterobacteriaceae ranged
      from 0.03 mg/l to 0.125 mg/l. Meropenem was very active against extended spectrum
      beta lactamase producing Klebsiella pneumoniae, most Acinetobacter species,
      Pseudomonas aeruginosa, Clostridium difficile (MIC90 of 1.0 mg/l), Clostridium
      perfringens and other Clostridium species. Even though imipenem exhibited better
      activity against the coagulase negative staphylococci, meropenem still had MIC's
      which were less than the break point (8.0 mg/l). The stability of meropenem in
      agar was determined indirectly by plotting the geometric mean MIC of control
      strains over a period of two weeks. Mean MIC of six control strains for meropenem
      was 0.05 mg/l and remained constant over 10 days, whereas the mean MIC of
      imipenem rose to 0.24 mg/l after two days and to 3.4 mg/l after 10 days.
      Meropenem was therefore far more stable in agar than imipenem. This has
      implications for laboratories using agar dilution as it requires less frequent
      plate preparation and decreased labour costs.

PMID- 9007957
TI  - Presence of strA-strB gene within a streptomycin-resistance operon in a clinical
      isolate of Shigella flexneri.
AB  - Three aminoglycoside-modifying enzymes (AMEs) were produced by a clinical isolate
      of Shigella flexneri which was resistant to gentamicin, tobramycin, netilmicin,
      kanamycin, sisomicin and streptomycin: acetyltransferase (AAC) (3)-II-type, and
      phosphotransferase (APH) (3")- and (6)-type enzymes. The aminoglycoside
      resistance genes were located on a 75-Kb plasmid. Two genes, strA-HK and strB-HK,
      in a transcriptional unit were found to code for streptomycin-resistance. The
      genetic organization and sequence of this transcriptional unit were identical to
      those of strA and strB in plasmid RSF1010. strA-HK and strB-HK when expressed
      separately produced functional enzymes. Our substrate profile study on the crude
      extracts of StrA-HK and StrB-HK proteins confirmed that StrA-HK was an APH(3")
      type and showed that StrB-HK was a member of the APH(6) family.

PMID- 9007958
TI  - Outbreak of gentamicin-resistant Acinetobacter baumanii in an intensive care
      unit: clinical, epidemiological and microbiological features.
AB  - The clinical, epidemiological and microbiological features of an outbreak of
      infection and colonisation caused by gentamicin-resistant Acinetobacter baumanii
      (GRAB) in an 18-bed intensive care unit (ICU) of a 680-bed adult teaching
      hospital are described. A retrospective review of medical, laboratory and
      infection control records was followed by prospective surveillance. Typing of
      isolates was performed by restriction enzyme analysis (REA) of chromosomal DNA.
      The incidence of GRAB in the ICU increased from 1.26 cases per 1000 occupied bed
      days (OBDs) for January to June 1993, to 6.62 per 1000 OBDs for July to December
      1993 (Chi square = 4.8, P < 0.05), confirming the existence of an outbreak. For
      the two year period, 1993 and 1994, a total of 45 cases of GRAB infection or
      colonisation was identified. Males and females were equally represented, with an
      age range of 16-79 years and a mean age of 51 years. Admitting diagnoses varied,
      with multiple trauma and head injury predominating (ten cases). For 35 of the 45
      cases the initial site of GRAB isolation was sputum or other respiratory tract
      specimen. Specific treatment for GRAB was initiated in 23 patients, however no
      deaths were directly attributable to GRAB infection. The period of time between
      admission to the ICU and first isolation of GRAB ranged from three to 70 days
      with a median of nine days. Overall, ten (11%) of 91 staff hand samples and one
      of 37 (3%) environmental samples yielded GRAB. All GRAB isolates produced similar
      biochemical profiles and antibiotic resistance patterns, except for a group of
      five which were ciprofloxacin resistant. Thirty patient isolates, all ten staff
      hand isolates and the environmental isolate produced identical REA patterns. The
      remaining five patient isolates (all ciprofloxacin resistant) which were
      available for typing produced a different REA pattern. Our study has documented a
      moderate-sized outbreak of GRAB in an ICU setting. Typing of isolates using REA
      was useful in delineating outbreak strains. Carriage of GRAB on staff hands was
      demonstrated as the most likely source of infection. Despite institution of
      infection control measures GRAB now appears endemic in the ICU.

PMID- 9007959
TI  - Subcutaneous zygomycosis due to Saksenaea vasiformis: rapid isolate
      identification using a modified sporulation technique.
AB  - Saksenaea vasiformis, a zygomycete belonging to the order Mucorales, is a rare
      cause of zygomycosis with 17 cases documented world-wide. It usually infects the
      immunocompromised or traumatized and has a high mortality rate. Because of its
      failure to sporulate under normal laboratory conditions it may be difficult to
      identify. We describe here an unusual case report of Saksenaea vasiformis with
      sporulation and identification within a week using a modified sporulation
      technique.

PMID- 9007960
TI  - Vancomycin and amikacin in cell cultures for virus isolation.
AB  - Contamination of cell cultures for virus isolation has been increasingly
      encountered. By reviewing and changing the antimicrobials incorporated in cell
      culture media, we aim to control this problem. Contaminated cell culture fluids
      were inoculated for bacterial and fungal isolation, identification and
      antibacterial susceptibility testing. Based on the above results, vancomycin and
      amikacin were chosen to replace the penicillin and gentamicin used
      conventionally. Analysis was carried out on various characteristics of cell
      culture with respect to antimicrobial change. All contaminating Gram-positive
      bacteria were susceptible to vancomycin while about 80% of the Gram-negative
      bacteria were sensitive to amikacin. The new antimicrobial combination was not
      toxic to cell cultures and both antimicrobials were found to remain stable in
      media for over six months. The virus isolation rate was maintained after
      antimicrobial change while the contamination rate was reduced from nearly 10% to
      1.5%. We thus conclude that vancomycin and amikacin can well replace the
      conventional penicillin and gentamicin to be incorporated into maintenance and
      transport media to control the emerging problem of viral culture contamination.

PMID- 9007961
TI  - The glandular odontogenic jaw cyst: report of a case.
AB  - A case of a rare odontogenic cyst arising in the lateral periodontal membrane in
      the mandible in a 14 year old girl is reported. This lesion appeared to be a new
      entity and has been named glandular odontogenic cyst (GOC) or sialo-odontogenic
      cyst. Histologically the lesion was lined by mucous producing cuboidal epithelium
      containing several areas of thickening and numerous duct-like structures. The
      cyst recurred with the same histology two years postoperatively.

PMID- 9007962
TI  - Cerebral and spinal cord myxopapillary ependymomas: a case report.
AB  - We report the case of a 16 year old male with a left temporal myxopapillary
      ependymoma which did not demonstrate any connection to the lateral ventricles.
      The patient had complained of headaches for ten months and signs of increased
      intracranial pressure for one month. One month post-operatively, because of lower
      back pain, further investigations disclosed two separate intraspinal
      myxopapillary ependymomas, one at T12-L1 level and the other at L5-S1 level. It
      is postulated that the cerebral myxopapillary ependymoma was in fact a secondary
      from one of the spinal cord tumors. There are only three reports of this type of
      ependymoma in the cerebrum.

PMID- 9007963
TI  - Massive amyloid deposition in pancreatic vipoma: a case report.
AB  - We present a case of a pancreatic islet cell tumor, demonstrating typical
      clinical and immunohistochemical characteristics of a VIPoma, but with the novel
      feature of massive stromal amyloid deposition. Amyloid deposition has been
      reported in association with insulinomas of the pancreas, but as far as the
      available literature suggests, it has not been reported in VIPomas. Islet
      associated polypeptide (IAPP) and calcitonin are both candidates for the
      amyloidogenic peptide in this case, based on observations in other tumors.

PMID- 9007965
TI  - Being a team physician.

PMID- 9007964
TI  - History of medicine revisited: does it give a glimpse into our future?

PMID- 9007966
TI  - General principles in treating soft-tissue injuries.
AB  - Most primary care physicians will encounter soft tissue injuries in their office.
      The acute treatment of these injuries using the acronym RICEM is the most
      important part of treatment so that the athlete may progress to a more functional
      phase of rehabilitation in older to allow for a rapid recovery and safe return to
      sport.

PMID- 9007967
TI  - Apophyseal injuries.

PMID- 9007968
TI  - Patellofemoral malalignment.
AB  - Anterior knee pain represents one of the most common musculoskeletal complaints
      of adolescents. It is a disorder in which there is broad clinical experience and
      yet it represents a difficult and frustrating entity for the athlete to endure
      and for the physician to treat. An appropriate clinical examination and selected
      diagnostic studies can define the diagnosis and the introduction of conservative
      therapy usually will correct the problem. Occasionally, surgical intervention is
      required, and debate remains as to the optimal techniques that should be used.

PMID- 9007969
TI  - The preparticipation athletic examination: a closer look.

PMID- 9007970
TI  - The acutely injured knee.
AB  - Determining the mechanism of injury is often helpful in making the diagnosis
      during the evaluation of the acutely injured knee. A few injuries require
      immediate orthopedic referral such as fractures, evidence of more than one
      sprained ligament, or neurovascular compromise. Most patients with acute knee
      injuries can be treated initially with crutches, ice, and analgesics. The key to
      rapid recovery of most injuries is a diligent rehabilitation program.

PMID- 9007971
TI  - Management of ankle sprains.
AB  - This article reviewed the basics of ankle diagnosis and rehabilitation. It is
      hoped that after reading this, pediatricians will have more confidence in caring
      for these injuries.

PMID- 9007973
TI  - Structure of the beta 2 homodimer of bacterial luciferase from Vibrio harveyi: X
      ray analysis of a kinetic protein folding trap.
AB  - Luciferase, as isolated from Vibrio harveyi, is an alpha beta heterodimer. When
      allowed to fold in the absence of the alpha subunit, either in vitro or in vivo,
      the beta subunit of enzyme will form a kinetically stable homodimer that does not
      unfold even after prolonged incubation in 5 M urea at pH 7.0 and 18 degrees C.
      This form of the beta subunit, arising via kinetic partitioning on the folding
      pathway, appears to constitute a kinetically trapped alternative to the
      heterodimeric enzyme (Sinclair JF, Ziegler MM, Baldwin TO. 1994. Kinetic
      partitioning during protein folding yields multiple native states. Nature Struct
      Biol 1: 320-326). Here we describe the X-ray crystal structure of the beta 2
      homodimer of luciferase from V. harveyi determined and refined at 1.95 A
      resolution. Crystals employed in the investigational belonged to the orthorhombic
      space group P2(1)2(1)2(1) with unit cell dimensions of a = 58.8 A, b = 62.0 A,
      and c = 218.2 A and contained one dimer per asymmetric unit. Like that observed
      in the functional luciferase alpha beta heterodimer, the major tertiary
      structural motif of each beta subunit consists of an (alpha/beta)8 barrel (Fisher
      AJ, Raushel FM, Baldwin TO, Rayment I. 1995. Three-dimensional structure of
      bacterial luciferase from Vibrio harveyi at 2.4 A resolution. Biochemistry 34:
      6581-6586). The root-mean-square deviation of the alpha-carbon coordinates
      between the beta subunits of the hetero- and homodimers is 0.7 A. This high
      resolution X-ray analysis demonstrated that "domain" or "loop" swapping has not
      occurred upon formation of the beta 2 homodimer and thus the stability of the
      beta 2 species to denaturation cannot be explained in such simple terms. In fact,
      the subunit:subunit interfaces observed in both the beta 2 homodimer and alpha
      beta heterodimer are remarkably similar in hydrogen-bonding patterns and buried
      surface areas.

PMID- 9007972
TI  - Friends and relations of the cystatin superfamily--new members and their
      evolution.
AB  - The cystatin "superfamily" encompasses proteins that contain multiple cystatin
      like sequences. Some of the members are active cysteine protease inhibitors,
      while others have lost or perhaps never acquired this inhibitory activity. In
      recent years, several new members of the superfamily have characterized,
      including proteins from insects and plants. Based on partial amino acid homology,
      new members, such as the invariant chain (Ii), and the transforming growth factor
      beta receptor type II (TGF-beta receptor II) may, in fact, represent members of
      an emerging family within the superfamily that may have used some common building
      blocks to form functionally diverse proteins. Cystatin super-family members have
      been found throughout evolution and members of each family of the superfamily are
      present in mammals today. In this review, the new and older, established members
      of the family are arranged into a possible evolutionary order, based on sequence
      homology and functional similarities.

PMID- 9007974
TI  - Hydrophobic folding units derived from dissimilar monomer structures and their
      interactions.
AB  - We have designed an automated procedure to cut a protein into compact hydrophobic
      folding units. The hydrophobic units are large enough to contain tertiary non
      local interactions, reflecting potential nucleation sites during protein folding.
      The quality of a hydrophobic folding unit is evaluated by four criteria. The
      first two correspond to visual characterization of a structural domain, namely,
      compactness and extent of isolation. We use the definition of Zehfus and Rose
      (Zehfus MH, Rose GD, 1986, Biochemistry 25:35-340) to calculate the compactness
      of a cut protein unit. The isolation of a unit is based on the solvent accessible
      surface area (ASA) originally buried in the interior and exposed to the solvent
      after cutting. The third quantity is the hydrophobicity, equivalent to the
      fraction of the buried non-polar ASA with respect to the total non-polar ASA. The
      last criterion in the evaluation of a folding unit is the number of segments it
      includes. To conform with the rationale of obtaining hydrophobic units, which may
      relate to early folding events, the hydrophobic interactions are implicitly and
      explicitly applied in their generation and assessment. We follow Holm and Sander
      (Holm L, Sander C, 1994, Proteins 19:256-268) to reduce the multiple cutting
      point problem to a one-dimensional search for all reasonable trial cuts. However,
      as here we focus on the hydrophobic cores, the contact matrix used to obtain the
      first non-trivial eigenvector contains only hydrophobic contracts, rather than
      all, hydrophobic and hydrophilic, interactions. This dataset of hydrophobic
      folding units, derived from structurally dissimilar single chain monomers, is
      particularly useful for investigations of the mechanism of protein folding. For
      cases where there are kinetic data, the one or more hydrophobic folding units
      generated for a protein correlate with the two or with the three-state folding
      process observed. We carry out extensive amino acid sequence order independent
      structural comparisons to generate a structurally non-redundant set of
      hydrophobic folding units for fold recognition and for statistical purposes.

PMID- 9007975
TI  - Probing the active site of alpha-class rat liver glutathione S-transferases using
      affinity labeling by monobromobimane.
AB  - Monobromobimane (mBBr) is a substrate of both mu- and alpha-class rat liver
      glutathione S-transferases, with Km values of 0.63 microM and 4.9 microM for the
      mu-class isozymes 3-3 and 4-4, respectively, and 26 microM for the alpha-class
      isozymes 1-1 and 2-2. In the absence of substrate glutathione, mBBr acts as an
      affinity label of the 1-1 as well as mu-class isozymes, but not of the alpha
      class 2-2 isozyme. Incubation of rat liver isozyme 1-1 with mBBr at pH 7.5 and 25
      degrees C results in a time-dependent inactivation of the enzyme but at a slower
      (threefold) rate than for reactions with the mu-class isozyme 3-3 and 4-4. The
      rate of inactivation of 1-1 isozyme by mBBr is not decreased but, rather, is
      slightly enhanced by S-methyl glutathione. In contrast, 17 beta-estradiol-3,17
      disulfate (500 microM) gives a 12.5-fold decrease in the observed rate constant
      of inactivation by 4 mM mBBr. When incubated for 60 min with 4 mM mBBr, the 1-1
      isozyme loses 60% of its activity and incorporates 1.7 mol reagent/mol subunit.
      Peptide analysis after thermolysin digestion indicates that mBBr modification is
      equally distributed between two cysteine residues at positions 17 and 111.
      Modification at these two sites is reduced equally in the presence of the added
      protectant, 17 beta-estradiol-3,17-disulfate, suggesting that Cys 17 and Cys 111
      reside within or near the enzyme's steroid binding sites. In contrast to the 1-1
      isozyme, the other alpha-class isozyme (2-2) is not inactivated by mBBr at
      concentrations as high as 15 mM. The different reaction kinetics and modification
      sites by mBBr suggest that distinct binding site structures are responsible for
      the characteristic substrate specificities of glutathione S-transferase isozymes.

PMID- 9007976
TI  - Studies of protein-protein interfaces: a statistical analysis of the hydrophobic
      effect.
AB  - Data sets of 362 structurally nonredundant protein-protein interfaces and of 57
      symmetry-related oligomeric interfaces have been used to explore whether the
      hydrophobic effect that guides protein folding is also the main driving force for
      protein-protein associations. The buried nonpolar surface area has been used to
      measure the hydrophobic effect. Our analysis indicates that, although the
      hydrophobic effect plays a dominant role in protein-protein binding, it is not as
      strong as that observed in the interior of protein monomers. Comparison of
      interiors of the monomers with those of the interfaces reveals that, in general,
      the hydrophobic amino acids are more frequent in the interior of the monomers
      than in the interior of the protein-protein interfaces. On the other hand, a
      higher proportion of charged and polar residues are buried at the interfaces,
      suggesting that hydrogen bonds and ion pairs contribute more to the stability of
      protein binding than to that of protein folding. Moreover, comparison of the
      interior of the interfaces to protein surfaces indicates that the interfaces are
      poorer in polar/charged than the surfaces and are richer in hydrophobic residues.
      The interior of the interfaces appears to constitute a compromise between the
      stabilization contributed by the hydrophobic effect on the one hand and avoiding
      patches on the protein surfaces that are too hydrophobic on the other. Such
      patches would be unfavorable for the unassociated monomers in solution. We
      conclude that, although the types of interactions are similar between protein
      protein interfaces and single-chain proteins overall, the contribution of the
      hydrophobic effect to protein-protein associations is not as strong as to protein
      folding. This implies that packing patterns and interatom, or interresidue,
      pairwise potential functions, derived from monomers, are not ideally suited to
      predicting and assessing ligand associations or design. These would perform
      adequately only in cases where the hydrophobic effect at the binding site is
      substantial.

PMID- 9007977
TI  - Solution structure of a unique C5a semi-synthetic antagonist: implications in
      receptor binding.
AB  - The tertiary structure of a unique C5a receptor antagonist was determined by two
      dimensional NMR spectroscopy. The core domain of this 8-kDa antagonist exists as
      an antiparallel helical bundle, similar to recombinant human (rh)-C5a. However,
      unlike C5a, the antagonist's C terminus was found to be conformationally
      restricted along a groove between helices one and four in the core domain. This
      conformational restriction situates C-terminal D-Arg 75 in a wedge between core
      residues Arg 46 and His 15. Correlation of the antagonist's tertiary structure
      with point mutation analysis revealed the formation of a positively charged
      contiguous contact surface comprised of D-Arg 75, Arg 46, Lys 49, and His 15. The
      significance of this surface in generating antagonist properties implies a single
      binding site with the C5a receptor and provides a structural template for drug
      design.

PMID- 9007978
TI  - Molecular modeling of the structures of human and rat pancreatic cholesterol
      esterases.
AB  - Structural models have been generated for rat and human cholesterol esterases by
      molecular modeling. For rat cholesterol esterase, three separate models were
      generated according to the following procedure: (1) the cholesterol esterase
      sequence was aligned with those of three template enzymes: Torpedo californica
      acetylcholinesterase, Geotrichum candidum lipase and Candida rugosa lipase; (2)
      the X-ray structure coordinates of the three template enzymes were used to
      construct cholesterol esterase models by amino acid replacements of matched
      sequence positions and by making sequence insertions and deletions as required;
      (3) bad contracts in each of the cholesterol esterase models were relaxed by
      molecular dynamics and mechanics; (4) the three cholesterol esterase models were
      merged into one by arithmetic averaging of atomic coordinates; (5) Ramachandran
      analysis indicated that the model generated from the AChE template possessed the
      best set of phi/psi angles. Therefore, this model was subjected to molecular
      dynamics, with harmonic constraints imposed on the C(alpha) coordinates to drive
      them toward the coordinates of the averaged model. (6) Subsequent relaxation by
      molecular mechanics produced the final rat cholesterol esterase model. A model
      for human cholesterol esterase was produced by repeating steps 1-3 above, albeit
      with the rat cholesterol esterase model as the template. Hydrophobic and
      electrostatic analyses of the rat and human cholesterol esterase models suggest
      the structural origins of molecular recognition of hydrophobic substrates and
      interfaces, of charged interfaces, and of bile salt activators.

PMID- 9007979
TI  - The crystal structure of the designed trimeric coiled coil coil-VaLd:
      implications for engineering crystals and supramolecular assemblies.
AB  - The three-dimensional structure of the 29-residue designed coiled coil having the
      amino acid sequence acetyl-E VEALEKK VAALESK VQALEKK VEALEHG-amide has been
      determined and refined to a crystallographic R-factor of 21.4% for all data from
      10-A to 2.1-A resolution. This molecule is called coil-VaLd because it contains
      valine in the a heptad positions and leucine in the d heptad positions. In the
      trigonal crystal, three molecules, related by a crystallographic threefold axis,
      form a parallel three-helix bundle. The bundles are stacked head-to-tail to form
      a continuous coiled coil along the c-direction of the crystal. The contacts among
      the three helices within the coiled coil are mainly hydrophobic: four layers of
      valine residues alternate with four layers of leucine residues to form the core
      of the bundle. In contrast, mostly hydrophilic contacts mediate the interaction
      between trimers: here a total of two direct protein--protein hydrogen bonds are
      found. Based on the structure, we propose a scheme for designing crystals of
      peptides containing continuous two-, three-, and four-stranded coiled coils.

PMID- 9007980
TI  - Importance of the release of strand 1C to the polymerization mechanism of
      inhibitory serpins.
AB  - Serpin polymerization is the underlying cause of several diseases, including
      thromboembolism, emphysema, liver cirrhosis, and angioedema. Understanding the
      structure of the polymers and the mechanism of polymerization is necessary to
      support rational design of therapeutic agents. Here we show that polymerization
      of antithrombin is sensitive to the addition of synthetic peptides that interact
      with the structure. A 12-m34 peptide (homologous to P14-P3 of antithrombin
      reactive loop), representing the entire length of s4A, prevented polymerization
      totally. A 6-mer peptide (homologous to P14-P9 of antithrombin) not only allowed
      polymerization to occur, but induced it. This effect could be blocked by the
      addition of a 5-mer peptide with s1C sequence of antithrombin or by an unrelated
      peptide representing residues 26-31 of cholecystokinin. The s1C or
      cholecystokinin peptide alone was unable to form a complex with native
      antithrombin. Moreover, an active antitrypsin double mutant, Pro 361-->Cys, Ser
      283-->Cys, was engineered for the purpose of forming a disulfide bond between s1C
      and s2C to prevent movement of s1C. This mutant was resistant to polymerization
      if the disulfide bridge was intact, but, under reducing conditions, it regained
      the potential to polymerize. We have also modeled long-chain serpin polymers with
      acceptable stereochemistry using two previously proposed loop-A-sheet and loop-C
      sheet polymerization mechanisms and have shown both to be sterically feasible, as
      are "mixed" linear polymers. We therefore conclude that the release of strand 1C
      must be an element of the mechanism of serpin polymerization.

PMID- 9007981
TI  - Conformation of P22 tailspike folding and aggregation intermediates probed by
      monoclonal antibodies.
AB  - The partitioning of partially folded polypeptide chains between correctly folded
      native states and off-pathway inclusion bodies is a critical reaction in
      biotechnology. Multimeric partially folded intermediates, representing early
      stages of the aggregation pathway for the P22 tailspike protein, have been
      trapped in the cold and isolated by nondenaturing polyacrylamide gel
      electrophoresis (PAGE) (speed MA, Wang DIC, King J. 1995. Protein Sci 4:900-908).
      Monoclonal antibodies against tailspike chains discriminate between folding
      intermediates and native states (Friguet B, Djavadi-Ohaniance L, King J, Goldberg
      ME. 1994. J Biol Chem 269:15945-15949). Here we describe a nondenaturing Western
      blot procedure to probe the conformation of productive folding intermediates and
      off-pathway aggregation intermediates. The aggregation intermediates displayed
      epitopes in common with productive folding intermediates but were not recognized
      by antibodies against native epitopes. The nonnative epitope on the folding and
      aggregation intermediates was located on the partially folded N-terminus,
      indicating that the N-terminus remained accessible and nonnative in the
      aggregated state. Antibodies against native epitopes blocked folding, but the
      monoclonal directed against the N-terminal epitope did not, indicating that the
      conformation of the N-terminus is not a key determinant of the productive folding
      and chain association pathway.

PMID- 9007982
TI  - Recombinant hirustasin: production in yeast, crystallization, and interaction
      with serine proteases.
AB  - A synthetic gene coding for the 55-amino acid protein hirustasin, a novel tissue
      kallikrein inhibitor from the leech Hirudo medicinalis, was generated by
      polymerase chain reaction using overlapping oligonucleotides, fused to the yeast
      alpha-factor leader sequence and expressed in Saccharomyces cerevisiae.
      Recombinant hirustasin was secreted mainly as incompletely processed fusion
      protein, but could be processed in vitro using a soluble variant of the yeast
      yscF protease. The processed hirustasin was purified to better than 97% purity. N
      terminal sequence analysis and electrospray ionization mass spectrometry
      confirmed a correctly processed N-terminus and the expected amino acid sequence
      and molecular mass. The biological activity of recombinant hirustasin was
      identical to that of the authentic leech protein. Crystallized hirustasin alone
      and in complex with tissue kallikrein diffracted beyond 1.4 A and 2.4 A,
      respectively. In order to define the reactive site of the inhibitor, the
      interaction of hirustasin with kallikrein, chymotrypsin, and trypsin was
      investigated by monitoring complex formation in solution as well as proteolytic
      cleavage of the inhibitor. During incubation with high, nearly equimolar
      concentration of tissue kallikrein, hirustasin was cleaved mainly at the peptide
      bond between Arg 30 and Ile 31, the putative reactive site, to yield a modified
      inhibitor. In the corresponding complex with chymotrypsin, mainly uncleaved
      hirustasin was found and cleaved hirustasin species accumulated only slowly.
      Incubation with trypsin led to several proteolytic cleavages in hirustasin with
      the primary scissile peptide bond located between Arg 30 and Ile 31. Hirustasin
      appears to fall into the class of protease inhibitors displaying temporary
      inhibition.

PMID- 9007983
TI  - Crystal structure of the reduced Schiff-base intermediate complex of
      transaldolase B from Escherichia coli: mechanistic implications for class I
      aldolases.
AB  - Transaldolase catalyzes transfer of a dihydroxyacetone moiety from a ketose donor
      to an aldose acceptor. During catalysis, a Schiff-base intermediate between
      dihydroxyacetone and the epsilon-amino group of a lysine residue at the active
      site of the enzyme is formed. This Schiff-base intermediate has been trapped by
      reduction with potassium borohydride, and the crystal structure of this complex
      has been determined at 2.2 A resolution. The overall structures of the complex
      and the native enzyme are very similar; formation of the intermediate induces no
      large conformational changes. The dihydroxyacetone moiety is covalently linked to
      the side chain of Lys 132 at the active site of the enzyme. The Cl hydroxyl group
      of the dihydroxyacetone moiety forms hydrogen bonds to the side chains of
      residues Asn 154 and Ser 176. The C3 hydroxyl group interacts with the side chain
      of Asp 17 and Asn 35. Based on the crystal structure of this complex a reaction
      mechanism for transaldolase is proposed.

PMID- 9007984
TI  - Identification of the cap binding domain of human recombinant eukaryotic protein
      synthesis initiation factor 4E using a photoaffinity analogue.
AB  - Binding of eIF-4E to the 5' m7G cap structure of eukaryotic mRNA signals the
      initiation of protein synthesis. In order to investigate the molecular basis for
      this recognition, photoaffinity labeling with [gamma-32P]8-N3GTP was used in
      binding site studies of human recombinant cap binding protein eIF-4E. Competitive
      inhibition of this cap analogue by m7GTP and capped mRNA indicated probe
      specificity for interaction at the protein binding site. Saturation of the
      binding site with [gamma-32P]8-N3GTP further demonstrated the selectivity of
      photoinsertion. Aluminum (III)-chelate chromatography and reverse-phase HPLC were
      used to isolate the binding site peptide resulting from digestion of photolabeled
      eIF-4E with modified trypsin. Amino acid sequencing identified the binding domain
      as the region containing the sequence Trp 113-Arg 122.Lys 119 was not identified
      in sequencing analysis nor was it cleaved by trypsin. These results indicate that
      Lys 119 is the residue directly modified by photoinsertion of [gamma-32P]8-N3GTP.
      A detailed understanding of eIF-4E.m7G mRNA cap interactions may lead the way to
      regulating this essential protein-RNA interaction for specific mRNA in vivo.

PMID- 9007985
TI  - Nonenzymatic anticoagulant activity of the mutant serine protease Ser360Ala
      activated protein C mediated by factor Va.
AB  - The human plasma serine protease, activated protein C (APC), primarily exerts its
      anticoagulant function by proteolytic inactivation of the blood coagulation
      cofactors Va and VIIIa. A recombinant active site Ser 360 to Ala mutation of
      protein C was prepared, and the mutant protein was expressed in human 293 kidney
      cells and purified. The activation peptide of the mutant protein C zymogen was
      cleaved by a snake venom activator, Protac C, but the "activated" S360A APC did
      not have amidolytic activity. However, it did exhibit significant anticoagulant
      activity both in clotting assays and in a purified protein assay system that
      measured prothrombinase activity. The S360A APC was compared to plasma-derived
      and wild-type recombinant APC. The anticoagulant activity of the mutant, but not
      native APC, was resistant to diisopropyl fluorophosphate, whereas all APCs were
      inhibited by monoclonal antibodies against APC. In contrast to native APC, S360A
      APC was not inactivated by serine protease inhibitors in plasma and did not bind
      to the highly reactive mutant protease inhibitor M358R alpha 1 antitrypsin. Since
      plasma serpins provide the major mechanism for inactivating APC in vivo, this
      suggests that S360A APC would have a long half-life in vivo, with potential
      therapeutic advantages. S360A APC rapidly inhibited factor Va in a nonenzymatic
      manner since it apparently did not proteolyze factor Va. These data suggest that
      native APC may exhibit rapid nonenzymatic anticoagulant activity followed by
      enzymatic irreversible proteolysis of factor Va. The results of clotting assays
      and prothrombinase assays showed that S360A APC could not inhibit the variant Gln
      506-FVa compared with normal Arg 506-FVa, suggesting that the active site of
      S360A APC binds to FVa at or near Arg 506.

PMID- 9007986
TI  - Thermodynamics of maltose binding protein unfolding.
AB  - The maltose binding protein (MBP or MalE) of Escherichia coli is the periplasmic
      component of the transport system for malto-oligosaccharides. It is used widely
      as a carrier protein for the production of recombinant fusion proteins. The
      melting of recombinant MBP was studied by differential scanning and titration
      calorimetry and fluorescence spectroscopy under different solvent conditions. MBP
      exhibits a single peak of heat absorption with a delta(Hcal)/delta(HvH) ratio in
      the range of 1.3-1.5, suggesting that the protein comprises two strongly
      interacting thermodynamic domains. Binding of maltose resulted in elevation of
      the Tm by 8-15 degrees C, depending of pH. The presence of ligand at neutral pH,
      in addition to shifting the melting process to higher temperature, caused it to
      become more cooperative. The delta(Hcal)/delta(HvH) ratio decreased to unity,
      indicating that the two domains melt together in a single two-state transition.
      This ligand-induced merging of the two domains appears to occur only at neutral
      pH, because at low pH maltose simply stabilized MBP and did not cause a decrease
      of the delta(Hcal)/delta(HvH) ratio. Binding of maltose to MBP is characterized
      by very low enthalpy changes, approximately -1 kcal/mol. The melting of MBP is
      accompanied by an exceptionally large change in heat capacity. 0.16 cal/K-g,
      which is consistent with the high amount of nonpolar surface--0.72 A2/g--that
      becomes accessible to solvent in the unfolded state. The high value of delta Cp
      determines a very steep delta G versus T profile for this protein and predicts
      that cold denaturation should occur above freezing temperatures. Evidence for
      this was provided by changes in fluorescence intensity upon cooling the protein.
      A sigmoidal cooperative transition with a midpoint near 5 degrees C was observed
      when MBP was cooled at low pH. Analysis of the melting of several fusion proteins
      containing MBP illustrated the feasibility of assessing the folding integrity of
      recombinant products prior to separating them from the MBP carrier protein.

PMID- 9007987
TI  - Structures of N-termini of helices in proteins.
AB  - We have surveyed 393 N-termini of alpha-helices and 156 N-termini of 3(10)
      helices in 85 high resolution, non-homologous protein crystal structures for N
      cap side-chain rotamer preferences, hydrogen bonding patterns, and solvent
      accessibilities. We find very strong rotamer preferences that are unique to N-cap
      sites. The following rules are generally observed for N-capping in alpha-helices:
      Thr and Ser N-cap side chains adopt the gauche - rotamer, hydrogen bond to the N3
      NH and have psi restricted to 164 +/- 8 degrees. Asp and Asn N-cap side chains
      either adopt the gauche - rotamer and hydrogen bond to the N3 NH with psi = 172
      +/- 10 degrees, or adopt the trans rotamer and hydrogen bond to both the N2 and
      N3 NH groups with psi = 1-7 +/- 19 degrees. With all other N-caps, the side chain
      is found in the gauche + rotamer so that the side chain does not interact
      unfavorably with the N-terminus by blocking solvation and psi is unrestricted. An
      i, i + 3 hydrogen bond from N3 NH to the N-cap backbone C = O in more likely to
      form at the N-terminus when an unfavorable N-cap is present. In the 3(10)-helix
      Asn and Asp remain favorable N-caps as they can hydrogen bond to the N2 NH while
      in the trans rotamer; in contrast, Ser and Thr are disfavored as their preferred
      hydrogen bonding partner (N3 NH) is inaccessible. This suggests that Ser is the
      optimum choice of N-cap when alpha-helix formation is to be encouraged while
      3(10)-helix formation discouraged. The strong energetic and structural
      preferences found for N-caps, which differ greatly from positions within helix
      interiors, suggest that N-caps should be treated explicitly in any consideration
      of helical structure in peptides or proteins.

PMID- 9007988
TI  - 3-Hydroxy-3-methylglutaryl-coenzyme A reductase of Haloferax volcanii: role of
      histidine 398 and attenuation of activity by introduction of negative charge at
      position 404.
AB  - Mutant 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductases of the
      halophilic archaeon Haloferax volcanii were constructed to test the proposed
      mechanism that phosphorylation downregulates the activity of higher eukarya HMG
      CoA reductases via charge-charge interaction with the active site histidine. To
      first verify the sequence-based inference that His 398 is the catalytic histidine
      of the H. volcanii enzyme, enzyme H398Q was constructed, purified, and assayed
      for catalysis of three reactions: [1] reductive deacylation of HMG-CoA, [2]
      reduction of mevaldehyde, and [3] oxidative acylation of mevaldehyde. Enzyme
      H398Q had low activity for catalysis of reaction [1] or [3], but readily
      catalyzed mevaldehyde reduction. By analogy to hamster HMG-CoA reductase, we
      conclude that His 398 is the active site histidine. Mutant forms of the 403
      residue H. volcanii enzyme were constructed to model phosphorylation and infer
      whether attenuated activity involved interaction with His 398. Chimeric H.
      volcanii-hamster enzymes constructed in an effort to create an active,
      phosphorylatable chimeric enzyme were inactive or not phosphorylated. We
      therefore added Asp at position 404 to mimic the introduction of negative charge
      that would accompany phosphorylation. Enzyme 404D/H398Q was inactive for reaction
      [1] or [3], but catalyzed reaction [2] at 35% the wild-type rate. These
      observations are consistent with the model that attenuation of catalytic activity
      results from an ionic interaction between the imidazolium cation of His 398 and
      the carboxylate anion of Asp 404.

PMID- 9007989
TI  - Conformational analysis of peptides corresponding to all the secondary structure
      elements of protein L B1 domain: secondary structure propensities are not
      conserved in proteins with the same fold.
AB  - The solution conformation of three peptides corresponding to the two beta
      hairpins and the alpha-helix of the protein L B1 domain have been analyzed by
      circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMR). In
      aqueous solution, the three peptides show low populations of native and non
      native locally folded structures, but no well-defined hairpin or helix structures
      are formed. In 30% aqueous trifluoroethanol (TFE), the peptide corresponding to
      the alpha-helix adopts a high populated helical conformation three residues
      longer than in the protein. The hairpin peptides aggregate in TFE, and no
      significant conformational change occurs in the NMR observable fraction of
      molecules. These results indicate that the helical peptide has a significant
      intrinsic tendency to adopt its native structure and that the hairpin sequences
      seem to be selected as non-helical. This suggests that these sequences favor the
      structure finally attained in the protein, but the contribution of the local
      interactions alone is not enough to drive the formation of a detectable
      population of native secondary structures. This pattern of secondary structure
      tendencies is different to those observed in two structurally related proteins:
      ubiquitin and the protein G B1 domain. The only common feature is a certain
      propensity of the helical segments to form the native structure. These results
      indicate that for a protein to fold, there is no need for large native-like
      secondary structure propensities, although a minimum tendency to avoid non-native
      structures and to favor native ones could be required.

PMID- 9007990
TI  - Heteronuclear (1H, 13C, 15N) NMR assignments and secondary structure of the basic
      region-helix-loop-helix domain of E47.
AB  - E47 is an immunoglobulin enhancer DNA-binding protein that contains a basic
      region-helix-loop-helix (b/HLH) domain. This structural motif defines a class of
      transcription factors that are central to the developmental regulation of many
      tissues. Its function is to provide a dimerization interface through the
      formation of a parallel four-helix bundle, resulting in the juxtaposition of two
      basic DNA-recognition alpha-helices that control sequence-specific DNA-binding.
      In order to gain insight into the biophysical nature of b/HLH domains, we have
      initiated structural studies of the E47 homodimer by NMR. Sequence-specific
      resonance assignments have been obtained using a combination of heteronuclear
      double- and triple-resonance NMR experiments. The secondary structure was
      deducted from characteristic patterns of NOEs, 13C (alpha)/beta chemical shifts,
      and measurements of 3JHNH alpha scalar couplings. Except for the basic region
      recognition helix, the secondary structural elements of the E47 homodimer are
      preserved in the absence DNA when compared with the co-crystal structure of E47
      bound to DNA (Ellenberger T, Fass D, Arnaud M, Harrison SC, 1994, Genes & Dev
      8:970-980). As expected, the DNA-binding helix is largely unstructured, but does
      show evidence of nascent helix formation. The HLH region of E47 is structured,
      but highly dynamic as judged by the rapid exchange of backbone hydrogen atoms and
      the relatively weak intensities of many of the NOEs defining the dimerization
      helices. This dynamic nature may be relevant to the ability of E47 both to
      homodimerize and to heterodimerize with MyoD, Id, and Tal1.

PMID- 9007991
TI  - gamma-Carboxyglutamic acids 36 and 40 do not contribute to human factor IX
      function.
AB  - The gamma-carboxyglutamic acid (Gla) domains of the vitamin K-dependent blood
      coagulation proteins contain 10 highly conserved Gla residues within the first 33
      residues, but factor IX is unique in possessing 2 additional Gla residues at
      positions 36 and 40. To determine their importance, factor IX species lacking
      these Gla residues were isolated from heterologously expressed human factor IX.
      Using ion-exchange chromatography, peptide mapping, mass spectrometry, and N
      terminal sequencing, we have purified and identified two partially carboxylated
      recombinant factor IX species; factor IX/gamma 40E is uncarboxylated at residue
      40 and factor IX/gamma 36,40E is uncarboxylated at both residues 36 and 40. These
      species were compared with the fully gamma-carboxylated recombinant factor IX,
      unfractionated recombinant factor IX, and plasma-derived factor IX. As monitored
      by anti-factor IX:Ca (II)-specific antibodies and by the quenching of intrinsic
      fluorescence, all these factor IX species underwent the Ca(II)-induced
      conformational transition required for phospholipid membrane binding and bound
      equivalently to phospholipid vesicles composed of phosphatidylserine,
      phosphatidylcholine, and phosphatidylethanolamine. Endothelial cell binding was
      also similar in all species, with half-maximal inhibition of the binding of 125I
      labeled plasma-derived factor IX at concentrations of 2-6 nM. Functionally,
      factor IX/gamma 36,40E and factor IX/gamma 40E were similar to fully gamma
      carboxylated recombinant factor IX and plasma-derived factor IX in their
      coagulant activity and in their ability to participate in the activation of
      factor X in the tenase complex both with synthetic phospholipid vesicles and
      activated platelets. However, Gla 36 and Gla 40 represent part of the epitope
      targeted by anti-factor IX:Mg(II)-specific antibodies because these antibodies
      bound factor IX preferentially to factor IX/gamma 36,40E and factor IX/gamma 40E.
      These results demonstrate that the gamma-carboxylation of glutamic acid residues
      36 and 40 in human factor IX is not required for any function of factor IX
      examined.

PMID- 9007992
TI  - Analysis of the structure and stability of omega loop A replacements in yeast iso
      1-cytochrome c.
AB  - Omega (omega)-loop A, residues 18-32 in wild-type yeast iso-1-cytochrome c, has
      been deleted and replaced with loop sequences from three other cytochromes c and
      one from esterase. Yeast expressing a partial loop deletion do not contain
      perceptible amounts of holoprotein as measured by low-temperature spectroscopy
      and cannot grow on nonfermentable media. Strains expressing loop replacement
      mutations accumulate holoprotein in vivo, but the protein function varies
      depending on the sequence and length of the replacement loop; in vivo expression
      levels do not correlate with their thermal denaturation temperatures. In vitro
      spectroscopic studies of the loop replacement proteins indicate that all fold
      into a native-like cytochrome c conformation, but are less stable than the wild
      type protein. Decreases in thermal stability are caused by perturbation of loop C
      backbone in one case and a slight reorganization of the protein hydrophobic core
      in another case, rather than rearrangement of the loop A backbone. A single-site
      mutation in one of the replacement mutants designed to relieve inefficient
      hydrophobic core packing caused by the new loop recovers some, but not all, of
      the lost stability.

PMID- 9007993
TI  - Mechanism of the stabilization of ribonuclease A by sorbitol: preferential
      hydration is greater for the denatured then for the native protein.
AB  - The effect of interactions of sorbitol with ribonuclease A (RNase A) and the
      resulting stabilization of structure was examined in parallel thermal unfolding
      and preferential binding studies with the application of multicomponent
      thermodynamic theory. The protein was stabilized by sorbitol both at pH 2.0 and
      pH 5.5 as the transition temperature, Tm, was increased. The enthalpy of the
      thermal denaturation had a small dependence on sorbitol concentration, which was
      reflected in the values of the standard free energy change of denaturation, delta
      delta G(o) = delta G(o) (sorbitol) - delta G(o)(water). Measurements of
      preferential interactions at 48 degrees C at pH 5.5, where protein is native, and
      pH 2.0 where it is denatured, showed that sorbitol is preferentially excluded
      from the denatured protein up to 40%, but becomes preferentially bound to native
      protein above 20% sorbitol. The chemical potential change on transferring the
      denatured RNase A from water to sorbitol solution is larger than that for the
      native protein, delta mu(2D) > delta mu(2N), which is consistent with the effect
      of sorbitol on the free energy change of denaturation. The conformity of these
      results to the thermodynamic expression of the effect of a co-solvent on
      denaturation, delta G(o)(W) + delta mu(D)(2)delta G(o)(S) + delta mu(2D),
      indicates that the stabilization of the protein by sorbitol can be fully
      accounted for by weak thermodynamic interactions at the protein surface that
      involve water reversible co-solvent exchange at thermodynamically non-neutral
      sites. The protein structure stabilizing action of sorbitol is driven by stronger
      exclusion from the unfolded protein than from the native structure.

PMID- 9007994
TI  - Temperature dependence of the preferential interactions of ribonuclease A in
      aqueous co-solvent systems: thermodynamic analysis.
AB  - The temperature dependence of preferential solvent interactions with ribonuclease
      A in aqueous solutions of 30% sorbitol, 0.6 M MgCl2, and 0.6 M MgSO4 at low pH
      (1.5 and 2.0) and high pH (5.5) has been investigated. This protein was
      stabilized by all three co-solvents, more so at low pH than high pH (expect 0.6 M
      MgCl2 at pH 5.5). The preferential hydration of protein in all three co-solvents
      was high at temperatures below 30 degrees C and decreased with a further increase
      in temperature (for 0.6 M MgCl2 at pH 5.5, this was not significant), indicating
      a greater thermodynamic instability at low temperature than at high temperature.
      The preferential hydration of denatured protein (low pH, high temperature) was
      always greater than that of native protein (high pH, high temperature). In 30%
      sorbitol, the interaction passed to preferential binding at 45% for native
      ribonuclease A and at 55 degrees C for the denatured protein. Availability of the
      temperature dependence of the variation with sorbitol concentration of the
      chemical potential of the protein, (delta mu(2)/delta m3)T,p,m2, permitted
      calculation of the corresponding enthalpy and entropy parameters. Combination
      with available data on sorbitol concentration dependence of this interaction
      parameter gave (approximate) values of the transfer enthalpy, delta H2,tr, and
      transfer entropy delta S2,tr. Transfer of ribonuclease A from water into 30%
      sorbitol is characterized by positive values of the transfer free energy,
      transfer enthalpy, transfer entropy, and transfer heat capacity. On denaturation,
      the transfer enthalpy becomes more positive. This increment, however, is small
      relative to both the enthalpy of unfolding in water and to the transfer enthalpy
      of the native protein from water a 30% sorbitol solution.

PMID- 9007995
TI  - Beta-turn propensities as paradigms for the analysis of structural motifs to
      engineer protein stability.
AB  - The thermodynamic stability of a protein provides an experimental metric for the
      relationship of protein sequence and native structure. We have investigated an
      approach based on an analysis of the structural database for stability
      engineering of an immunoglobulin variable domain. The most frequently occurring
      residues in specific positions of beta-turn motifs were predicted to increase the
      folding stability of mutants that were constructed by site-directed mutagenesis.
      Even in positions in which different residues are conserved in immunoglobulin
      sequences, the predictions were confirmed. Frequently, mutants with increased
      beta-turn propensities display increased folding cooperativities, suggesting
      pronounced effects on the unfolded state independent of the expected effect on
      conformational entropy. We conclude that structural motifs with predominantly
      local interactions can serve as templates with which patterns of sequence
      preferences can be extracted from the database of protein structures. Such
      preferences can predict the stability effects of mutations for protein
      engineering and design.

PMID- 9007996
TI  - Crystallization and preliminary crystallographic analysis of recombinant human
      P38 MAP kinase.
AB  - The recombinant human p38 MAP kinase has been expressed and purified from both
      Escherichia coli and SF9 cells, and has been crystallized in two forms by the
      hanging drop vapor diffusion method using PEG as precipitant. Both crystal forms
      belong to space group P2(1)2(1)2(1). The cell parameters for crystal form 1 are a
      = 65.2 A, b = 74.6 A and c = 78.1 A. Those for crystal form 2 are a = 58.3 A, b =
      68.3 A and c = 87.9 A. Diffraction data to 2.0 A resolution have been collected
      on both forms.

PMID- 9007997
TI  - LPFC: an Internet library of protein family core structures.
AB  - As the number of protein molecules with known, high-resolution structures
      increases, it becomes necessary to organize these structures for rapid retrieval,
      comparison, and analysis. The Protein Data Bank (PDB) currently contains nearly
      5,000 entries and is growing exponentially. Most new structures are similar
      structurally to ones reported previously and can be grouped into families. As the
      number of members in each family increases, it becomes possible to summarize,
      statistically, the commonalities and differences within each family. We reported
      previously a method for finding the atoms in a family alignment that have low
      spatial variance and those that have higher spatial variance (i.e., the "core"
      atoms that have the same relative position in all family members and the "non
      core" atoms that do not). The core structures we compute have biological
      significance and provide an excellent quantitative and visual summary of a
      multiple structural alignment. In order to extend their utility, we have
      constructed a library of protein family cores, accessible over the World Wide Web
      at http:/ /www-smi.stanford.edu/projects/helix/LPFC/. This library is generated
      automatically with publicly available computer programs requiring only a set of
      multiple alignments as input. It contains quantitative analysis of the spatial
      variation of atoms within each protein family, the coordinates of the average
      core structures derived from the families, and display files (in bitmap and VRML
      formats). Here, we describe the resource and illustrate its applicability by
      comparing three multiple alignments of the globin family. These three alignments
      are found to be similar, but with some significant differences related to the
      diversity of family members and the specific method used for alignment.

PMID- 9007998
TI  - SAM as a protein interaction domain involved in developmental regulation.
AB  - More than 60 previously undetected SAM domain-containing proteins have been
      identified using profile searching methods. Among these are over 40 EPH-related
      receptor tyrosine kinases (RPTK), Drosophila bicaudal-C, a p53 from Loligo
      forbesi, and diacyglycerol-kinase isoform delta. This extended dataset suggests
      that SAM is an evolutionary conserved protein binding domain that is involved in
      the regulation of numerous developmental processes among diverse eukaryotes. A
      conserved tyrosine in the SAM sequences of the EPH related RPTKs is likely to
      mediate cell-cell initiated signal transduction via the binding of SH2 containing
      proteins to phosphotyrosine.

PMID- 9008000
TI  - Occupational exposure to electromagnetic fields and adult leukaemia: a review of
      the epidemiological evidence.
AB  - The relationship between occupational exposure to extremely low-frequency
      electromagnetic fields and adult leukaemia has been studied extensively during
      the last decade. The first studies were based on crude exposure assessments,
      estimated through job titles, with no or only limited control confounding
      factors. The results were often inconsistent, indicating no effects in about 50%
      of the studies, while the other half showed only small to moderate effects.
      Concern has been raised that crude exposure-assessment methods might have diluted
      the effect estimates, and that improvement of the methods used for exposure
      assessment would result in more consistent associations. The present review
      emphasises the latest studies with considerably improved exposure assessments, as
      well as the control of confounding factors. Results from studies where exposure
      was assessed through measurements of the magnetic fields at the workplace are
      still inconsistent. These studies provide some support for the hypothesis of an
      association between magnetic field exposure and adult leukaemia, especially for
      chronic lymphocytic leukaemia, but inconsistencies between and within studies
      weaken the evidence. The lack of consistency regarding the type of leukaemia
      associated with magnetic field exposure might be explained by differences between
      the study designs or the populations studied, but based on the existing evidence,
      no firm conclusions can be drawn.

PMID- 9007999
TI  - Vitamins, metabolic antagonists, and molecular evolution.

PMID- 9008001
TI  - PARATI--a dynamic model for radiological assessments in urban areas. Part I.
      Modelling of urban areas, their contamination and radiation fields.
AB  - The structure and mathematical model of PARATI, a detailed computer programme
      developed for the assessment of the radiological consequences of an accidental
      contamination of urban areas, is described with respect to the scenarios used for
      the estimation of exposure fields in a village or town, the models for the
      initial and secondary contamination with the radionuclide 137Cs, the concepts for
      calculating the resulting radiation exposures and the changes with time of the
      contamination and radiation fields. Kerma rates at various locations in tropical
      urban areas are given, and the contribution of different contaminated surfaces to
      these rates after dry or wet deposition are discussed.

PMID- 9008002
TI  - A comparative study of microdosimetric properties of x-rays, gamma-rays, and beta
      rays.
AB  - The objective of this study was the computation of microdosimetric functions and
      quantities for sparsely ionizing radiations. The calculations are performed on
      simulated electron tracks generated by Monte-Carlo techniques. Ten different
      radiations of biomedical interest are considered. The comparison of radiation
      qualities shows marked differences between these sparsely ionizing radiations.
      The microdosimetric date are represented graphically for use in radiation biology
      and in clinical applications.

PMID- 9008003
TI  - Effects of cell cycle specific exposure to 3H-thymidine or 3H-arginine on
      development and cell proliferation of mouse embryos.
AB  - One-cell mouse embryos were exposed to either 3H-thymidine (100 or 200 kBq/ml) or
      3H-arginine (2.5 to 50 kBq/ml) for 2 h either in G1, S or G2 phase. 3H-Arginine
      affected embryonic development and cell proliferation in an activity-dependent
      way irrespective of the cell cycle stage exposed, whereas 3H-thymidine was
      effective only at higher activities and only after exposure during S phase.

PMID- 9008004
TI  - Persistent expression of morphological abnormalities in the distant progeny of
      irradiated cells.
AB  - The phenomenon of delayed heritable lethal damage (often referred to as "lethal
      mutations") in the progeny of cells which survive irradiation is now well
      established, but little is known of the mechanism by which this cell death
      occurs. Current theories suggest a generalised genomic instability affecting all
      cells which leads to the production of some mutations which are lethal, or
      alternatively that a lethal mutation gene is activated, mutated or induced by
      radiation and leads to persistent and random cell death at high levels in the
      progeny. The aim of this study was to look at the morphology of progeny of
      irradiated cells at various times after irradiation to establish how widespread
      morphological abnormalities were in the population and whether there was any
      evidence that such abnormalities were clonal. Using two different cell lines, the
      results showed that morphological evidence possibly suggestive of apoptosis
      occurred in the cultures after all doses of radiation and up to 45 cell doublings
      after exposure. There was no evidence of a decrease in the numbers of damaged or
      dead cells in colonies with number of divisions after irradiation, or with
      decreasing original radiation dose. There was a significant dose-dependent
      increase in the number of cells with microvilli for both cell lines. The dose
      dependency of this effect did not change with number of divisions after
      irradiation. It is clear that morphological evidence of cellular damage persists
      for several generations after the initial exposure. The effects are widespread in
      the cell population, and their constancy over time argues strongly for a general
      instability and against a clonal mechanism, since clonal descendants should die
      out and leave undamaged survivors. The lack of evidence for necrosis or
      senescence together with many morphological changes in the cultures suggestive of
      apoptosis could indicate an active mechanism of cell death. It is concluded that
      survivor populations of irradiated cells from two widely different mammalian cell
      lines demonstrate an altered phenotype including gross morphological changes.
      These result in a higher probability that cell division will fail to yield two
      healthy progeny.

PMID- 9008005
TI  - Natural beta-carotene and whole body irradiation in rats.
AB  - beta-carotene and other carotenoids are reported to be potent free radical
      quenchers, singlet oxygen scavengers, and lipid antioxidants. Whole-body
      irradiation is known to cause an immunosuppression effect in mammals through the
      possible initiation and production of reactive oxygen species. We decided to test
      the possible antioxidative effect against whole-body irradiation of a natural
      beta-carotene, composed of equal amounts of the all-trans and 9-cis isomers,
      obtained from the unicellular alga Dunaliella bardawil. Rats were fed on ground
      commercial food enriched with natural beta-carotene (50 mg/kg diet). On
      completion of 1 week with beta-carotene, the rats were exposed to a single dose
      of 4 Gy whole-body irradiation, after which their livers and blood were removed
      for beta-carotene and retinol analysis in comparison with control livers of
      animals irradiated or not, or supplemented with beta-carotene after irradiation.
      A normal increase in body weight with no ill effects was noted in the groups of
      rats whose diet was supplemented by beta-carotene before and after irradiation,
      compared with the reduction in the specific growth rate in the group of rats
      irradiated without beta-carotene. Liver beta-carotene and retinol decreased
      significantly after irradiation compared with the rats which were not irradiated.
      This decrease was not shown in rats fed beta-carotene prior to irradiation, and
      the effect of irradiation was partially cured by supplementation with beta
      carotene after irradiation. High-pressure liquid chromatography (HPLC) analysis
      of the irradiated animals showed a selective decline in 9-cis beta-carotene and
      in retinol over all-trans beta-carotene and retinyl-esters. These results suggest
      that 9-cis beta-carotene and retinol protect in vivo against the cellular damage
      by free radicals induced after whole-body irradiation.

PMID- 9008006
TI  - Membrane oxidative damage induced by ionizing radiation detected by fluorescence
      polarization.
AB  - Effects of ionizing radiation on biological membranes include alterations in
      membrane proteins, peroxidation of unsaturated lipids accompanied by
      perturbations of the lipid bilayer polarity. We have measured radiation-induced
      membrane modifications using two fluorescent lipophilic membrane probes (TMA-DPH
      and DPH) by the technique of fluorescence polarization on two different cell
      lines (Chinese hamster ovary CHO-K1 and lymphoblastic RPMI 1788 cell lines).
      gamma-Irradiation was performed using a 60Co source with dose rates of 0.1 and 1
      Gy/min for final doses of 4 and 8 Gy. Irradiation induced a decrease of
      fluorescence intensity and anisotropy of DPH and TMA-DPH in both cell lines,
      which was dose-dependent but varied inversely with the dose rate. Moreover, the
      fluorescence anisotropy measured in lymphoblastic cells using TMA-DPH was found
      to decrease as early as 1 h after irradiation, and remained significantly lower
      24 h after irradiation. This study indicates that some alterations of membrane
      fluidity are observed after low irradiation doses and for some time thereafter.
      The changes in membrane fluidity might reflect oxidative damage, thus confirming
      a radiation-induced fluidization of biological membranes. The use of membrane
      fluidity changes as a potential biological indicator of radiation injury is
      discussed.

PMID- 9008007
TI  - In situ gamma-spectrometry several years after deposition of radiocesium. Part I.
      Approximation of depth distributions by the Lorentz function.
AB  - Several years after the deposition of fallout-radiocesium, the maximal activity
      of this radionuclide will not remain at the soil surface but be found rather in
      deeper layers. In order to estimate the total radiocesium contamination of a
      large area and the resulting gamma-dose rate by in-situ spectrometry, it is
      necessary to approximate the vertical distribution of this radionuclide by an
      analytical function. Observations at ten undisturbed grassland soils and Bavaria,
      Germany, show that the resulting depth distributions can be approximated closely
      by a three-parameter Lorentz function. This function characterises the observed
      distributions in all three critical sections, i.e. the surface layer, the
      distribution around the maximal concentration, and the tail at greater depth. It
      is also shown that the observed total activity per unit area of the soil due to
      137Cs agrees very well with the corresponding value obtained from the integrated
      Lorentz function. The two coefficients of the Lorentz function, which
      characterise the location (depth) and width of the maximum in the activity
      distribution, are shown to be correlated. In part II of this study, it will be
      shown how the parameters of the Lorentz function can also be obtained by in-situ
      gamma-ray spectrometry. As a result, it is possible to use in-situ gamma-ray
      spectrometry to obtain the total 137Cs activity per unit area also for sites
      where the vertical distribution of this radionuclide in the soil is no longer
      exponential.

PMID- 9008008
TI  - Pilot study of the Urals population by tooth electron paramagnetic resonance
      dosimetry.
AB  - During 1949-1956, about 76 x 10(6)m3 of radioactive liquid waste containing a
      total activity of 10(17) Bq was discharged into the Techa River by the first
      Russian industrial nuclear facility Mayak. As a consequence, the population
      living in the river valley received considerable internal and external radiation
      doses. The results of a first application of electron paramagnetic resonance
      (EPR) of tooth enamel for a retrospective individual dose evaluation of the
      residents of the Techa riverside are presented. Three main contributions to the
      dose absorbed in tooth enamel have been considered: external exposure mainly from
      the Techa River sediments, internal exposure mainly due to 90Sr; and background
      radiation including all other sources of exposure except the Techa River. The
      teeth of 86 inhabitants of the town Kamensk-Uralskii were analysed to determine
      the age-dependent contribution of the background radiation to the enamel dose.
      For 22 residents of the middle and lower Techa riverside, measurements of the
      90Sr whole-body content and EPR measurements of the absorbed dose in enamel were
      used to establish a correlation between these two quantities. Finally, absorbed
      doses in the enamel of five residents of the upper Techa riverside were
      determined by EPR method. Contributions of the background radiation and the
      internal 90Sr contamination were subtracted to determine the external exposure of
      the residents.

PMID- 9008009
TI  - Dose dependent of sister chromatid exchanges in humans lymphocytes induced by in
      vitro alpha-particle irradiation.
AB  - Exposure of human G0 lymphocytes to high-LET particles under different conditions
      has been seen, unlike low-LET radiations, to be substantially effective in the
      induction of sister chromatid exchanges (SCE). However, whereas for fast neutrons
      a linear dose response of SCE has been determined, there is no sign of a dose
      response relationship for alpha-particles. A likely reason for this lack of dose
      dependence may be the irradiation procedure. Therefore, a technique developed in
      our laboratory to ensure uniformity of irradiation with alpha-particles was used
      in the present study. Monolayers of 3 h-stimulated lymphocytes were exposed with
      alpha-particles from 241Am. Underdispersion was found for the cell-to-cell
      variance of the number of SCE. The dose response of SCE was linear, with a yield
      of 3.4 SCE per cell and per Gray.

PMID- 9008010
TI  - On the formation kinetics of radiation-induced chromosome exchanges in human
      lymphocytes.

PMID- 9008012
TI  - Thanks for the inspiration.

PMID- 9008011
TI  - The baccalaureate isn't for everyone.

PMID- 9008013
TI  - Chemotherapy and prostate cancer.

PMID- 9008014
TI  - 1996 John Cahoon Jr Memorial Lecture. Principles, politics and power.

PMID- 9008015
TI  - Medical imaging of trauma to the upper cervical spine.
AB  - This article provides a comprehensive look at trauma to the upper cervical spine.
      It begins with an in-depth discussion of vertebral anatomy, then focuses on types
      of cervical trauma and examines the diagnostic techniques used to image cervical
      trauma.

PMID- 9008016
TI  - Computed radiography: its impact on radiographers.
AB  - Computed radiography, a form of digital imaging, is being introduced in radiology
      departments across the country. Although many articles have been written about
      the advantages of computed radiography, little has been published regarding the
      technology's impact on radiographers' day-to-day practice. This article reviews
      the technology behind computed radiography and examines the tasks that
      radiographers need to learn in order to process digital images.

PMID- 9008017
TI  - Model for cultural diversity in the radiology department.
AB  - This article describes a model used in the nursing profession to promote an
      understanding of cultural diversity among employees and patients of health care
      facilities. The model addresses six factors important in cultural expression:
      communication, space, social organization, time, environmental control and
      biological variations. Managers in radiology departments can use the model as the
      basis for an educational in-service for employees and to build diverse, yet
      cohesive, work teams. The model also can be used as the basis for further
      scientific investigation into cultural diversity in diagnostic imaging and
      radiation therapy.

PMID- 9008018
TI  - Evidence is in: begin mammography at 40.

PMID- 9008019
TI  - Magnification mammography.

PMID- 9008020
TI  - Developmental hip and pelvis radiology.

PMID- 9008021
TI  - Improving student skills with CBL.

PMID- 9008022
TI  - N-acetyl-beta-D-glucosaminidase excretion in calcium oxalate stone patients and
      its relation to the risk of stone formation.
AB  - A tubular renal damage induced by crystals in the renal tubuli can be the
      triggering primary but also secondary cause of stone formation. In 72 calcium
      oxalate stone patients (45 men, 27 women) N-acetyl-beta-D-glucosaminidase [NAG]
      excretion in 24h-urine was investigated. 48 healthy test persons (27 men, 21
      women) served as a control group and helped to establish reference values. In
      order to find out a possible relation between NAG reference values and the risks
      of urolithiasis, lithogenous and inhibitory substances were determined in both
      groups. In the following, relative calcium oxalate supersaturation, representing
      a risk of urinary stone formation, was analyzed and compared to NAG excretion
      values. The threshold value of pathologic NAG excretion was determined in the
      group of healthy test subjects (mean value +/- 2 standard deviation) and was
      fixed at 4.2 U/d (women 3.06 U/d, men 4.24 U/d). In our investigations on NAG
      excretion significantly (p < 0.05) increased values were found in stone patients
      (4.43 U/d +/- 4.27) as compared to healthy test persons (2.13 U/d +/- 1.02). In
      the case of increased NAG excretion in stone patients there was a positive
      correlation between NAG excretion and increased phosphate, sulphate, uric acid,
      oxalate, and creatinine excretion. Only in female patients there was a relation
      between relative calcium oxalate supersaturation and NAG excretion values. As a
      result, NAG determination is considered to be an appropriate means of tracing a
      certain risk group within calcium oxalate stone patients.

PMID- 9008023
TI  - Proliferating cell nuclear antigen expression in renal cell carcinoma. Prognostic
      implications.
AB  - The proliferating cell nuclear antigen (PCNA) is a nuclear protein associated
      with cells in active cell cycle. The expression of PCNA was evaluated
      immunohistochemically in 3-6 samples from 68 renal cell carcinomas. A total of
      279 tumour samples were analysed using the monoclonal antibody PC-10, and the
      percentage of positively stained cell nuclei (PCNA-index) was determined. The
      tumour PCNA-index varied between 0.9-17.5%, with a mean value of 4.9%,
      significantly different from normal kidney cortex samples (p < 0.001). A
      significant difference in PCNA-index was found between the different tumour
      grades, whereas no significant difference was found between clinical stages.
      Concerning DNA ploidy, aneuploid tumours had a significantly higher PCNA-index
      compared with diploid tumours (p = 0.002). There was a significant survival
      advantage for patients with low tumour PCNA-indices (< 3.5%) compared with those
      with high indices (> 3.5%, p = 0.019), a difference also found for patients with
      non-metastatic disease (p = 0.012). Our data shows that PCNA expression can be
      analysed and that it may constitute an additional prognostic parameter for
      patients with renal cell carcinoma.

PMID- 9008024
TI  - A population-based analysis of survival and incidental diagnosing of renal cell
      carcinoma patients in Iceland, 1971-1990.
AB  - The significance of incidental diagnosing in relation to survival of renal cell
      carcinoma (RCC) patients is not known. A retrospective, population-based study
      was carried out in order to evaluate the survival of RCC patients, with emphasis
      on incidental diagnosing. Included in the study were all patients diagnosed with
      RCC in Iceland between 1971 and 1990. The tumours were classified and the extent
      of the disease staged by Robson's method. Crude probability of survival was
      evaluated for every stage, and multivariate analysis applied in order to
      determine prognostic factors. Out of 408 patients, 15% were diagnosed
      incidentally between 1971 and 1980 and 20% between 1981 and 1990 (p > 0.1), most
      often by intravenous urography. Only 5 tumours were detected incidentally by
      ultrasound techniques and 4 by CT scans. Crude five-year survival was 76% for
      stage I disease and 11% for stage IV disease. After correction for staging by
      multivariate analysis, incidental diagnosis and the year of diagnosis were not
      independent significant prognostic factors for mortality. As in many other
      studies, our data indicate that incidentally diagnosed RCCs are at a lower stage
      at the time of diagnosis. On the other hand, the results of our population-based
      study show that ultrasound and CT scanning have not significantly increased the
      number of incidentally diagnosed tumours. It is therefore not very surprising
      that surviving of RCC patients in Iceland has remained the same for the last two
      decades.

PMID- 9008025
TI  - Urodynamic and rectomanometric findings in urinary incontinence.
AB  - To investigate the correlation of urinary and fecal incontinence, 52 patients
      with urinary incontinence underwent cystometry and rectomanometry. Twenty-five
      patients suffered from stress, 20 from urge and 7 from overflow urinary
      incontinence. The rectomanometry showed normal results in 29 patients, 5
      presented with a compensated and 18 with a partially compensated sphincter
      incompetence. Whereas 18 of 20 urge incontinent patients had a normal rectal
      sphincter function, in contrast 16 of 25 stress incontinent patients suffered
      from rectal sphincter incompetence. In conclusion, there is a marked correlation
      between stress urinary incontinence and rectal sphincter incompetence. This
      supports the general thesis that a weakness of the entire pelvic floor is one of
      the characteristic features of urinary incontinence.

PMID- 9008026
TI  - Carcinoma of the bladder in patients under 25 years of age.
AB  - A review of our records between 1971 and 1995 identified 6 patients (4 male and 2
      female) with transitional cell carcinoma of the bladder who were less than 25
      years of age (mean age 18.6, range 10-22). Five patients presented with gross
      haematuria, one with microscopic haematuria, and two presented with recurrent
      urinary tract infection. All tumours were low grade and low stage and were
      associated with excellent prognosis. Transurethral resection or fulguration was
      the treatment of choice. This study supports the contention that transitional
      cell carcinoma of the bladder is a less aggressive disease in patients under 25
      years of age.

PMID- 9008027
TI  - A study of female urinary incontinence in general practice. Demography, medical
      history, and clinical findings.
AB  - The aim of this study was to provide valid data on the demography, medical
      history and clinical findings among adult women presenting with urinary
      incontinence to general practitioners. In a rural community in Norway, all women
      > 20 years who consulted their general practitioner for urinary incontinence
      during a 3 year period were included in a prospective study. A thorough medical
      history and both a general and focused clinical examination were undertaken.
      Gynecological examination, stress provocation test, and 48 h frequency/volume
      chart and pad weighing test were also performed. 105 women were included (4.4% of
      women > 20 years in the total population). Mean age was 57 years, 64% were
      postmenopausal. A lot of comorbidity was reported. Duration of incontinence was >
      5 years in 49%. By a severity index, 64% were classified as severe, 28% as
      moderate and 8% as having slight incontinence. 59% were using protective pads or
      garments. Mean leakage per 24 h was 31 g. 38% had significant genital prolapse.
      Contractility of the pelvic floor muscles was weak in 28%. Diagnostic
      classification revealed 50% stress incontinence, 10% urge and 40% mixed
      incontinence. 42% of the patients were a great deal or much bothered by their
      incontinence. Patients with stress incontinence were less bothered than others.
      Women presenting with urinary incontinence at a primary care level are prevalent,
      and often have significant incontinence. It is a challenge for the general
      practitioners to investigate and treat these patients optimally.

PMID- 9008028
TI  - Urinary incontinence and sexual impotence after radical prostatectomy.
AB  - Telephone interviews concerning urinary continence and sexual potency in 152 men
      who had undergone radical prostatectomy for localized cancer were conducted by an
      investigator who had not been involved in the patients' treatment. The obtained
      data were compared with the surgeons' recorded follow-up notes. Continence was
      defined according to ICS criteria and potency as the capacity for vaginal
      penetration. At the interviews, 74 men (49%) reported total continence and 39
      others (26%) were acceptably dry; 32 required more than two small protective pads
      per day, five had received an artificial sphincter implant and two had
      supravesical urinary diversion (Kock pouch), making 39 (25%) classified as
      incontinent. The surgeons' records, however, showed an 89% continence rate and
      87% of these men had regained continence within 24 weeks of the operation. Of 134
      preoperatively potent men, only 21 (14%) remained potent in the first
      postoperative year. That earlier reported excellent results regarding continence
      and potency were not reproduced in our study, possible was partly due to our
      inclusion of more advanced tumours in somewhat older patients, but the fact that
      the interviewer was independent of the surgeon significantly influenced the
      results.

PMID- 9008029
TI  - Diagnostic and therapeutic laparoscopy of the nonpalpable testis.
AB  - We report about laparoscopic examination and treatment of 19 patients with 25 non
      palpable testes. Thirteen patients presented with unilateral and six patients
      with bilateral absent testes, respectively. In all cases of non-palpable testes
      laparoscopy was able to determine the exact localization and supported the
      surgical approach. Six testicles were treated by open orchiectomy after
      diagnostic laparoscopy; three testes were fixed by laparoscopically assisted
      orchiopexy. Three patients (three testicles) were treated by standard orchiopexy
      after laparoscopy and in three cases microvascular autotransplantation was
      performed. Laparoscopically, five aplastic testicles without vas and vessels were
      diagnosed. Three testes were considered as vanishing and in two patients (two
      testes) due to previous surgical exploration elsewhere testicular remnants were
      totally atrophic and were resected with the adjacent vas. All laparoscopic
      findings except the vanishing testis syndrome were proven either by open surgery
      or by laparoscopic preparation of the internal inguinal ring.

PMID- 9008030
TI  - Treatment of chronic hepatitis B and C with alpha interferon in a renal
      transplant patient.
AB  - We report the case of a 51-year-old renal transplant patient, treated by
      interferon alpha (5MUI, three times a week) since he presented a coinfection by
      hepatitis B (HBV) and hepatitis C (HCV) virus for more than 7 years, associated
      with a chronic increase in serum alanine aminotransferase (ALT) levels and a
      chronic active hepatitis. The 4-month treatment was associated with a sustained
      normalization of ALT, a disappearance of HBV replication and a transient
      clearance of HCV viremia. Side effects were moderate and included thrombopenia
      (90,000/mm3), leucopenia (2200/mm3), an increase in serum creatinine (178
      mumol/l). The withdrawal of alpha interferon was associated with the correction
      of these parameters. No rejection was observed on kidney biopsy. Meanwhile, liver
      histology was not affected by the treatment. To date, nineteen months after the
      end of alpha interferon therapy HBV DNA was still negative; ALT remained normal
      despite the early recurrence of HCV viremia; this emphasized the fact that HBV
      infection was certainly the most important factor involved in the patient's
      chronic hepatitis. It is concluded that alpha interferon therapy is able to
      decline HBV replication for a prolonged period in renal transplant patient
      although its use should be performed with caution due to the potential renal side
      effects.

PMID- 9008031
TI  - Spontaneous caval tumor thrombus necrosis and regression of pulmonary lesions in
      renal cell cancer.
AB  - Idiopathic regression of metastases is one of the features of the unpredictable
      behaviour of renal cell carcinoma. We report a patient with pulmonary metastases
      and a tumor thrombus in the inferior vena cava with spontaneous regression of the
      lung lesions and necrosis of the thrombus before any therapy was instituted.

PMID- 9008033
TI  - Bladder neck leiomyoma causing obstructive renal failure.

PMID- 9008032
TI  - Uraemia due to ureteric obstruction of a solitary kidney by a vaginal ring
      pessary.
AB  - An 81-year-old woman with a solitary left kidney presented with uraemia due to
      ureteric obstruction by a vaginal ring pessary. She made a complete recovery
      following removal of the pessary.

PMID- 9008034
TI  - Neurofibromatosis of the bladder.
AB  - Multiple neurofibromatosis, von Recklinghausen's disease, is a rare disease of
      the neurilemmal cells. It is an inherited disorder transmitted as a mendelian
      dominant and characterized by multiple subcutaneous tumours and cafe-au-lait
      spots. The first time its symptoms were described was by Smith in 1849.

PMID- 9008035
TI  - Cystosarcoma phyllodes of the prostate.
AB  - We report a case of a 40-year-old man with cystosarcoma phyllodes of the
      prostate. This tumour is very rare in the prostate. The stroma of the tumour was
      cellular and composed of elongated cells with spindle shaped nuclei, scanty, pale
      and eosinophilic cytoplasm. Some cells showed nuclear atypia but the cells did
      not display mitotic activity. We categorised this tumour as benign. The
      suprapubic prostatectomy was done. The patient is alive and well after three
      years.

PMID- 9008036
TI  - Two cases of small cell carcinoma of the prostate.
AB  - We describe the clinical and pathological findings in two Japanese men with small
      cell carcinoma of the prostate; case 1 was 58 years old and case 2 was 24 years
      old. Case 1 was initially diagnosed as a poorly differentiated adenocarcinoma of
      the prostate, stage D2, with marked elevation of serum neuron-specific enolase
      (NSE), carcinoembryonic antigen (CEA), and CA 19-9 levels. The patient had
      undergone castration and systemic chemotherapy. After three courses of
      chemotherapy, tumour markers were normalized. However, 6 months later serum
      levels of tumour markers again rose, and biopsy of the prostate revealed a small
      cell carcinoma component in the adenocarcinoma of the prostate and benign
      prostate hypertrophy. The patient was again treated with systemic chemotherapy
      but died within 1 year after relapse. In case 2, the patient presented with
      initial symptoms of lumbago and dysuria, and an enlarged prostate was
      radiologically diagnosed. Shortly after admission he developed ileus, and an
      exploratory laparotomy revealed a large tumour arising from the prostate and
      invading the peritoneal cavity. This tumour was pathologically diagnosed as a
      small cell carcinoma. The patient died shortly thereafter without responding to
      chemotherapy. Immunohistological evaluation was done using a panel of antibodies
      against NSE, chromogranin A, CEA, CA 19-9, prostatic acid phosphatase (PAP),
      prostate-specific antigen (PSA), leukocyte common antigen (LCA), epithelial
      membrane antigen (EMA), adrenocorticotropic hormone (ACTH), calcitonin,
      serotonin, gastrin, vasoactive intestinal peptide (VIP), and glucagon. CEA was
      intensely positive in the tumour lesions from case 1, and NSE and ACTH were
      focally positive, and calcitonin, serotonin, CA 19-9, and PSA were weakly
      positive only in several cells in the tumour lesions from case 1. In the tumour
      lesion from case 2, NSE was intensely positive, and chromogranin A was weakly
      positive. These findings support the neuroendocrine nature of this neoplasm.

PMID- 9008037
TI  - Progression from adenocarcinoma to small cell carcinoma of the prostate with
      normalization of prostate-specific antigen (PSA) levels.
AB  - We report a case of prostatic cancer in which transformation from adenocarcinoma
      into small cell carcinoma was demonstrated both by histology and
      immunohistochemistry. This phenomenon supports the hypothesis that small cell
      carcinoma of the prostate originates from multipotential prostatic epithelial
      cells.

PMID- 9008038
TI  - Contralateral testicular torsion after previous unilateral orchiopexy for
      undescended testis.
AB  - Torsion of testis after previous fixation of the same testis has been described
      several times. Contralateral torsion of unilateral fixed testis might result in
      subfertility. Four cases of later torsion of the contralateral testis after
      previous orchiopexy for unilateral undescended testis are presented along with a
      review of the literature.

PMID- 9008039
TI  - Priapism following ingestion of papaverine tablets.
AB  - A case of priapism following oral intake of papaverine hydrochloride (300 mg) is
      reported. The priapism persisted after coitus. It resisted conservative
      treatment, but responded to aspiration of the corpora cavernosa and irrigation
      with phenylephrine solution. We found no earlier report of priapism induced by
      oral papaverine. The possible therapeutic role of oral papaverine in impotence
      merits study.

PMID- 9008040
TI  - Traumatic injury of the penis: surgical management.
AB  - Three cases of penile injury secondary to mishap during sexual intercourse are
      described. The injury involved unilateral corpus cavernosum associated with
      urethral rupture in one case, penile fracture in the second patient and isolated
      urethral fracture in the third. Diagnosis and treatment of these uncommon lesions
      are discussed.

PMID- 9008041
TI  - Evaporated extracts of samples for pesticide residue analysis simplifies
      transport from remote places.

PMID- 9008042
TI  - Identification of mixed O-phenyl alkyl phthalate esters in an agricultural land.

PMID- 9008043
TI  - Spectroscopic study of soil particle surface redox reactions.

PMID- 9008044
TI  - Dynamics of chlordane under nonconstant exposure conditions: a numerical
      bioaccumulation model.

PMID- 9008045
TI  - Quantitative structure-activity relationship studies of selected heterocyclic
      nitrogen compounds.

PMID- 9008046
TI  - Chromium(III) sorption enhancement through NTA--modification of biological
      materials.

PMID- 9008047
TI  - Rapid toxicity estimation using soil ciliates: sensitivity and bioavailability.

PMID- 9008048
TI  - Mutagenic activity of incense smoke in comparison to formaldehyde and
      acetaldehyde in Salmonella typhimurium TA102.

PMID- 9008050
TI  - Chronic lead exposure in children living in Miskolc, Hungary, on the basis of
      teeth lead levels.

PMID- 9008049
TI  - Acute hepatotoxic potential of imazalil fungicide in rats.

PMID- 9008051
TI  - Effects of azadirachtin on mortality, growth, and immunological function in the
      wolf spider, Schizocosa episina (Araneae: Lycosidae).

PMID- 9008052
TI  - Role of testosterone in ameliorating the cadmium induced inhibition of thyroid
      function in adult male mouse.

PMID- 9008053
TI  - Masculinization of mosquitofish as an indicator of exposure to kraft mill
      effluent.

PMID- 9008054
TI  - Effects of sublethal exposure to zinc chloride on the reproduction of the water
      flea, Moina irrasa (Cladocera).

PMID- 9008055
TI  - Stress-related changes in cunner, Tautogolabrus adspersus, living near a paper
      mill.

PMID- 9008056
TI  - 1-Nitropyrene-metabolizing activities of fish liver preparations.

PMID- 9008057
TI  - Cadmium-induced changes in the histology of kidneys in common carp, Cyprinus
      carpio (Cyprinidae).

PMID- 9008058
TI  - Effect of pesticides on the diazotrophic growth and nitrogenase activity of
      purple nonsulfur bacteria.

PMID- 9008059
TI  - Toxicity of phenol on Macrobrachium rosenbergii (de Man) eggs, larvae, and post
      larvae.

PMID- 9008061
TI  - Response of three microbial test systems to pesticides.

PMID- 9008063
TI  - Accumulation and elimination of pentachlorophenol in the freshwater bivalve
      Corbicula fluminea.

PMID- 9008060
TI  - Toxicity of Abate to green frog tadpoles.

PMID- 9008062
TI  - Accumulation and depuration of tributyltin oxide and its effect on the
      fertilization and embryonic development in the pacific oyster, Crassostrea gigas.

PMID- 9008064
TI  - Effect of cadmium chloride on the distal retinal pigment cells of the fiddler
      crab, Uca pugilator.

PMID- 9008065
TI  - FORUM: The Converging Dynamics of Interest Representation in ResourcesManagement
AB  - / The role of the public in resource management has undergone aprofound
      transformation over the past two decades. Public input has evolvedfrom the
      enthusiasm for the widespread emergence public participation in theearly 1970s,
      through the realization of the relative effectiveness and costsof lobbying
      activities in the 1980s, to the emergence of environmentaldispute resolution
      (EDR) as a promising new alternative for the 1990s.Throughout this changing
      dynamic, there has been little attention tofundamental conception. This paper
      addresses this lack of conceptualization.A model of convergence is proposed to
      explain this transformation and as thebasis for an improved understanding of
      effective interest representationstrategies. The defining characteristics of
      lobbying, public participation,and environmental dispute resolution in resources
      management are outlinedrelative to the publics they involve, interest activity,
      organization,influence on policy, participatory features, and empowerment.
      Knowledge ofthese aspects will further aid in the identification and
      implementation ofeffective strategies to interest representation on a context
      specific basis.KEY WORDS: Interest representation; Public participation;
      Disputeresolution; Lobbying; Resource management

PMID- 9008066
TI  - Environmental Policy in Russia: Economic, Legal, and OrganizationalIssues
AB  - / Despite the suspension and closing down of many pollutingindustrial facilities
      and corresponding expectations of positive change inthat field, it is argued that
      the environmental situation in Russia in thefirst half of the 1990s has not
      improved. To corroborate this point, thelatest available data are presented and
      the deep roots and complexities ofthe current socioeconomic and political
      situation in the country areanalyzed. Using analogies and "component accounting"
      approaches,the original economic assessments of environmental damage in the
      recent pastand current period in Russia are offered for comparison with similar
      datafrom a selection of developed countries. A model of a new
      environmentalstrategy and policy is developed and its economic, legal, and
      organizationaldimensions are examined.KEY WORDS: Damage; Environmental costs;
      Policy; Pollution; Publicparticipation; Risk; Strategy

PMID- 9008067
TI  - PROFILE: Indigenous Institutions and Environmental Assessment: The Caseof Ghana
AB  - / The search for sustainable development provides the impetus forexamining the
      role of indigenous institutions and their ecological knowledgein environmental
      assessment and local sustainability. This paper attempts totrace the evolution of
      environmental assessment in Ghana. Focusing on theAshanti Region, the paper
      further discusses the nature and operations ofindigenous institutions, their
      ecological knowledge, beliefs, practices, andsocial norms that are relevant to
      environmental assessment process in thecountry. Some of the challenges that
      emerge from the discussions arehighlighted. There is a need to establish
      environmental assessment andcooperative management boards that would include
      representatives ofindigenous institutions. In addition, the introduction of
      technicaldictionaries and training manuals based on indigenous ecological
      knowledgeand their humane environmental practices will further improve
      theenvironmental assessment process in Ghana.KEY WORDS: Environmental assessment;
      Indigenous institutions; Indigenousecological knowledge; Sustainable development;
      Environmental assessmentboards

PMID- 9008068
TI  - Toward Integrated Resource Management: Lessons About the EcosystemApproach from
      the Laurentian Great Lakes
AB  - / The ecosystem approach is an innovative tool for integratedresource management.
      Its goal is to restore, enhance, and protect ecosystemintegrity through a
      holistic and integrated mode of planning. Under thisapproach, the ecosystem
      itself becomes the unit of analysis and organizingprinciple for environmental
      management. Utilizing the ecosystem approachchallenges the prevailing structure
      and function of contemporary resourcemanagement agencies. This paper explores a
      number of important policy andmanagement issues in the context of a ten-year
      initiative to remediate theLaurentian Great Lakes using the ecosystem approach.
      The lessons gleaned fromthe Great Lakes experience are relevant to other areas in
      North America andabroad where resource management responsibilities are held by
      multiple andsometimes overlapping jurisdictions.KEY WORDS: Integrated resource
      management; Ecosystem approach; Watershedmanagement; Great Lakes

PMID- 9008069
TI  - Changes in Land Cover and Subsequent Effects on Lower Fraser BasinEcosystems from
      1827 to 1990
AB  - / European settlement began in the Lower Fraser Basin (LFB) inwestern British
      Columbia in 1827 and has impacted the basin ecosystem in anumber of ways,
      especially affecting the vegetation. Using previouslypublished data, air photos,
      and other historical material for the area,estimates of land cover were made for
      the years prior to 1827 and for 1930and 1990. The area of coniferous forest
      changed from 71% prior to 1827to 50% in 1930 to 54% in 1990. However, prior to
      1827, only27% of the forest would have been immature (<120 years old), while40%
      would have been immature in 1930 and 73% of the forest wasimmature in 1990. The
      amount of wetland area decreased from 10% to1% of the study area while urban and
      agricultural area increased to26% of the study area by 1990. The changes in land
      cover have hadadverse effects on soil, water, and air quality; aquatic life; and
      plant andanimal populations. Estimates of changes in net primary production
      andorganic soil carbon suggest a decline over the past 170 years, although
      thelatter rate of decrease has slowed since 1930. As human populations in
      theLower Fraser Basin continue to increase, the quality of air, water, and
      soilwill continue to decline unless measures are taken.KEY WORDS: Human impact;
      Land cover; Net primary productivity; Organiccarbon in soil

PMID- 9008070
TI  - Acid Volatile Sulfides, Equilibrium Partitioning, and HazardousWaste Site
      Sediments
AB  - / Information provided by acid volatile sulfide (AVS) andequilibrium partitioning
      (EqP) theory is described, including two caseexamples, relative to hazardous
      waste site sediments. AVS and EqP are toolsin the toolbox, which can serve three
      main functions: screening,prioritization, and assisting in explaining observed
      effects. They should notbe used in isolation for decision making, particularly at
      hazardous waste orother sites where the sediments are contaminated by materials
      such as coal,coke, and pitch.KEY WORDS: Acid volatile sulfides; Equilibrium
      partitioning; Sediments;Hazardous waste

PMID- 9008071
TI  - Biological Effects of Fine Sediment in the Lotic Environment
AB  - / Although sedimentation is a naturally occurring phenomenon inrivers, land-use
      changes have resulted in an increase in anthropogenicallyinduced fine sediment
      deposition. Poorly managed agricultural practices,mineral extraction, and
      construction can result in an increase in suspendedsolids and sedimentation in
      rivers and streams, leading to a decline inhabitat quality. The nature and
      origins of fine sediments in the loticenvironment are reviewed in relation to
      channel and nonchannel sources andthe impact of human activity. Fine sediment
      transport and deposition areoutlined in relation to variations in streamflow and
      particle sizecharacteristics. A holistic approach to the problems associated with
      finesediment is outlined to aid in the identification of sediment
      sources,transport, and deposition processes in the river catchment. The
      multiplecauses and deleterious impacts associated with fine sediments on
      riverinehabitats, primary producers, macroinvertebrates, and fisheries are
      identifiedand reviewed to provide river managers with a guide to source material.
      Therestoration of rivers with fine sediment problems are discussed in relationto
      a holistic management framework to aid in the planning and undertaking
      ofmitigation measures within both the river channel and surrounding
      catchmentarea.KEY WORDS: Sedimentation; Fine sediment; Holistic approach;
      Ecologicalimpact; River restoration

PMID- 9008073
TI  - Wilderness Quality and Visitors' Wilderness Attitudes: ManagementImplications
AB  - / This study examines whether or not wilderness visitors'attitudes toward
      wilderness are related to the quality of the wilderness thathas been visited.
      From three Ontario, Canada, provincial parks (Algonquin,Killarney, and Quetico),
      a sample of 540 wilderness campers was randomlyselected from a total of 138,317
      campers. People sampled ranged in age from15 to 75 years with a mean of slightly
      over 37. They were highly educated. Amajority of them resided in urban or
      suburban areas. Significant correlationsbetween visitors' levels of wilderness
      attitudes and wilderness qualitywere found. However, wilderness quality evaluated
      by wilderness visitors(subjective quality) did not agree with that evaluated by
      the wildernessmanagers (objective quality).KEY WORDS: Wilderness; Attitudes;
      Subjective quality; Objectivequality

PMID- 9008074
TI  - Effects of Recreational Impacts on Soil Microbial Communities
AB  - / The functional diversity of soil microbial communities in heavilyimpacted
      subalpine campsites and adjacent undisturbed areas was comparedusing the Biolog
      method of carbon utilization profiles. Principal componentsanalysis of patterns
      and level of microbial activity indicate that microbialcommunities differentiate
      in response to disturbance in the top 6 cm of soil,while below 6 cm there were no
      recognizable differences between disturbed andundisturbed soil communities.
      Analysis of the factors that differentiate theupper microbial communities between
      disturbed and undisturbed sites revealedthat the percent of total carbon sources
      utilized was significantly less inthe disturbed (54%) than in undisturbed areas
      (95%). Carbonsubstrates important in the discrimination between soil communities
      includeplant, invertebrate, and microbial derivatives that could not be
      metabolizedby microbial communities from disturbed sites. Comparisons of
      totalculturable actinomycetes, bacteria, and fungi reveal no difference in
      overallnumber of colony forming units (CFU) on disturbed and undisturbed sites,
      buta marked decrease in actinomycetes on disturbed sites. Biolog andspread-plate
      data combined indicate a shift in the structure and function ofthe microbial
      community in campsite soils, which may be a useful indicator ofsoil community
      disturbance.KEY WORDS: Microbial functional diversity; Anthropogenic
      disturbance;Recreational impacts; Carbon source profile; Subalpine

PMID- 9008072
TI  - RESEARCH: Issues Related to Greenhouse Effect, ProductivityModeling, and Nutrient
      Cycling: A Case Study of Indian Wetlands
AB  - / Models available in the literature on nutrient uptake, lightavailability, and
      chlorophyll growth have been suitably modified andintegrated through the computer
      program CHLORF (written in "C"language), which has the advantage of being
      amenable to simulation undervarious combinations of input variables. The model
      has been used forsensitivity analysis in order to identify the most sensitive set
      ofparameters whose control can form an appropriate basis for evolving
      pragmaticmanagement strategies. In addition, greenhouse mitigation potential has
      beencomputed in terms of assimilation of carbon dioxide for a case study ofIndian
      wetlands.KEY WORDS: Wetland; Nutrient cycling; Modeling; Greenhouse effect

PMID- 9008075
TI  - State Park Directors' Perceptions of Mountain Biking
AB  - / This study intended to explore the perceptions of mountain bikingmanagement
      through a mail survey of state park directors in all 50 states.With a 100%
      response rate, it was found that 47 states permit mountainbiking in their state
      parks, however, few state parks have formalized plansto manage this outdoor
      activity. The management policies that do exist arenot followed on a statewide
      basis but vary within each state and at eachstate park. Many states have worked
      cooperatively with local mountain bikingclubs to develop and maintain mountain
      bike trails, promote rider education,and provide volunteer patrols on trails. The
      issue of user conflict surfacedwith almost three-fourths of the managers
      responding that conflict existedbetween mountain bikers and other trail users.
      This preliminary study shouldprompt further research with on-site managers
      focusing on the use ofmanagement plans for mountain biking, cooperation between
      managers and usergroups, and user conflict. It is recommended that an Internet
      basedinformation clearinghouse or discussion group be made available to
      landmanagers by a national bicycling organization.KEY WORDS: Mountain biking;
      State parks; State park directors;Recreation resource management

PMID- 9008076
TI  - A Conceptual Framework for Selecting and Analyzing Stressor Data toStudy Species
      Richness at Large Spatial Scales
AB  - / In this paper we develop a conceptual framework for selectingstressor data and
      analyzing their relationship to geographic patterns ofspecies richness at large
      spatial scales. Aspects of climate and topography,which are not stressors per se,
      have been most strongly linked withgeographic patterns of species richness at
      large spatial scales (e.g.,continental to global scales). The adverse impact of
      stressors (e.g., habitatloss, pollution) on species has been demonstrated
      primarily on much smallerspatial scales. To date, there has been a lack of
      conceptual developmenton how to use stressor data to study geographic patterns of
      speciesrichness at large spatial scales.The framework we developed includes four
      components: (1) clarification of theterms stress and stressor and categorization
      of factors affecting speciesrichness into three groups-anthropogenic stressors,
      natural stressors, andnatural covariates; (2) synthesis of the existing
      hypotheses for explaininggeographic patterns of species richness to identify the
      scales over whichstressors and natural covariates influence species richness and
      to providesupporting evidence for these relationships through review of
      previousstudies; (3) identification of three criteria for selection of stressor
      andcovariate data sets: (a) inclusion of data sets from each of the
      threecategories identified in item 1, (b) inclusion of data sets
      representingdifferent aspects of each category, and (c) to the extent possible,
      analysisof data quality; and (4) identification of two approaches for
      examiningscale-dependent relationships among stressors, covariates, and patterns
      ofspecies richness-scaling-up and regression-tree analyses.Based on this
      framework, we propose 10 data sets as a minimum data base forexamining the
      effects of stressors and covariates on species richness atlarge spatial scales.
      These data sets include land cover, roads, wetlands(numbers and loss), exotic
      species, livestock grazing, surface water pH,pesticide application, climate (and
      weather), topography, and streams.KEY WORDS: Anthropogenic impacts; Biodiversity;
      Environmental gradients;Geographic information systems; Hierarchy

PMID- 9008077
TI  - Perceptions of Species Abundance, Distribution, and Diversity:Lessons from Four
      Decades of Sampling on a Government-Managed Reserve
AB  - / We examined data relative to species abundance, distribution, anddiversity
      patterns of reptiles and amphibians to determine how perceptionschange over time
      and with level of sampling effort. Location data werecompiled on more than one
      million individual captures or observations of 98species during a 44-year study
      period on the US Department of Energy's(DOE) Savannah River Site National
      Environmental Research Park (SRS-NERP) inSouth Carolina. We suggest that
      perceptions of herpetofaunal speciesdiversity are strongly dependent on level of
      effort and that land managementdecisions based on short-term data bases for some
      faunal groups could resultin serious errors in environmental management. We
      provide evidence thatacquiring information on biodiversity distribution patterns
      is compatiblewith multiyear spatially extensive research programs and also
      provide aperspective of what might be achieved if long-term, coordinated
      researchefforts were instituted nationwide.To conduct biotic surveys on
      government-managed lands, we recommend revisionsin the methods used by government
      agencies to acquire and report biodiversitydata. We suggest that government and
      industry employees engaged inbiodiversity survey efforts develop proficiency in
      field identification forone or more major taxonomic groups and be encouraged to
      measure the status ofpopulations quantitatively with consistent and reliable
      methodologies. Wealso suggest that widespread academic cooperation in the
      dissemination ofinformation on regional patterns of biodiversity could result
      byestablishment of a peer-reviewed, scientifically rigorous journal concernedwith
      status and trends of the biota of the United States. KEY WORDS: Abundance;
      Amphibian; Biodiversity; Distribution; Landmanagement; Reptile

PMID- 9008078
TI  - Nitrogen Balance in the Lower Fraser River Basin of British Columbia
AB  - / A study was conducted to determine the extent of nitrogenpollution in
      agricultural lands in the Lower Fraser River basin of BritishColumbia, Canada.
      The specific objectives were to determine the distributionof leachable
      nitrogenand estimate the nitrogen concentration in groundwaterrecharges. Nitrogen
      and water mass balances were conducted on the entirebasin and on each of the four
      districts comprising it over the period1971-1991 in intervals of five years. The
      results indicated that the averagenitrogen concentration in the groundwater
      recharge for the entire basin rosefrom nondetectable in 1971 to 6 mg/liter in
      1991. Estimates for theindividual districts ranged from 4 to 14 mg/liter in
      Central Fraser and fromnondetectable to 7 mg/liter in Fraser-Cheam and 3 mg/liter
      in both GreaterVancouver and Dewdney-Alouette. So far, excessive levels of
      nitrogen areconfined to Central Fraser. Although they have remained within the
      acceptablerange, nitrogen concentrations in the other three districts have
      definitelyincreased over the 20-year study period. Sensitivity analyses indicated
      thatanimal manure and fertilizer had the largest contribution in
      groundwaterrecharge. Decreasing the rate of manure application to agricultural
      lands issuggested as the most practical way of reducing nitrogen pollution in
      CentralFraser.KEY WORDS: Nitrogen balance; Water balance; Sensitivity analysis

PMID- 9008079
TI  - Denitrification Distributions in Four Valley and Ridge RiparianEcosystems
AB  - / Denitrification in riparian ecosystems can reduce the amount ofnitrogen
      transported from farm fields to streams. In this study, we examinedenitrification
      in four riparian ecosystems common to the Valley and Ridgephysiographic province
      in Pennsylvania, USA. The sites exhibit differentvegetation, are underlain by
      different rock types, and are downgradient offarm fields. Mean site
      denitrification rates ranging from 0.6 to 1.9 &mgr;gN/kg soil/day were measured
      using intact core incubation techniques. Thethree riparian sites covered with
      grass each exhibited greaterdenitrification rates than the wooded site.
      Denitrification rate wascorrelated with moisture content but not with nitrate-N
      or organic carboncontents. Denitrification rates were greatest near the soil
      surface and atpositions nearest the stream. Rates decreased uniformly with
      distance awayfrom the stream and also with depth in the soil for each site. While
      patternsof nitrate-N, moisture, and organic carbon content differ among the
      sites,their combined effects on denitrification support the observed,
      consistentdenitrification rate pattern.KEY WORDS: Denitrification; Riparian
      ecosystems

PMID- 9008080
TI  - ENVIRONMENTAL AUDITING: Exceedance of Critical Loads for Lakes inFinland, Norway,
      and Sweden: Reduction Requirements for AcidifyingNitrogen and Sulfur Deposition
AB  - / The main objectives of this study were to identify the regions inFennoscandia
      where the critical loads of sulfur (S) and acidifying nitrogen(N) for lakes are
      exceeded and to investigate the consequences for depositionreductions, with
      special emphasis on the possible trade-offs between S and Ndeposition in order to
      achieve nonexceedance. In the steady-state model forcalculating critical loads
      and their exceedances, all relevant processesacting assinks for N and S are
      considered. The critical loads of N and S areinterrelated (defining the so-called
      critical load function), and therefore asingle critical load for one pollutant
      cannot be defined without makingassumptions about the other. Comparing the
      present N and S deposition withthe critical load function for each lake allows
      determination of thepercentage of lakes in the different regions of Fennoscandia
      where: (1) Sreductions alone can achieve nonexceedance, (2) N reductions alone
      aresufficient, and (3) both N and S reductions are required but to a
      certaindegree interchangeable. Secondly, deposition reduction requirements
      wereassessed by fixing the N deposition to the present level, in this
      wayanalyzing the reductions required for S, and by computing the percentage
      oflakes exceeded in Finland, Norway and Sweden for every possible
      percentdeposition reduction in S and N, in this way showing the
      (relative)effectiveness of reducing S and/or N deposition. The results showed
      clearregional patterns in the S and N reduction requirements. In practically
      thewhole of Finland and the northern parts of Scandinavia man-made
      acidificationof surface waters could be avoided by reducing S deposition alone.
      In thesouthern parts of Sweden some reductions in N deposition are clearly
      neededin addition to those for S. In southern Norway strong reductions are
      requiredfor both N and S deposition.KEY WORDS: Acidification; Critical load;
      Exceedance; Sulfur; Nitrogen;Deposition; Lake

PMID- 9008093
TI  - Endoscopic mucosal resection.

PMID- 9008094
TI  - In situ hybridization study on human papillomavirus DNA expression in benign and
      malignant squamous lesions of the esophagus.
AB  - Histologic changes suggesting HPV infection are occasionally found adjacent to
      squamous cell carcinoma or in squamous papilloma of the esophagus, but the
      relationship between HPV infection and benign and malignant squamous lesions of
      the esophagus is not yet dear. The aim of this study was to examine the role of
      HPV in squamous lesions of the esophagus. Microscopic examination with emphasis
      on HPV infection was done on 15 cases of squamous cell carcinoma and 26 cases of
      squamous papilloma. In situ hybridization technique for wide-spectrum HPV probe
      was performed on 35 endoscopically biopsied esophageal tissues. Among the
      histologic parameters suggesting HPV infection, acanthosis was the most frequent
      finding: 100.0% in benign and malignant esophageal lesions, and koilocytosis and
      intraepithelial capillary loops were the second (92.7%).: Dyskeratosis, basal
      cell hyperplasia and bi- or multinucleation were 52.3%, 44.0% and 34.1% in
      frequency, respectively. On in situ hybridization study, the HPV DNA expression
      rates of 10 squamous cell carcinomas with evidence of HPV infection and 15
      carcinomas without evidence of HPV infection were 60.0% and 33.3%, respectively.
      In contrast to the carcinoma cases, only one (10.0%) of 10 squamous papillomas
      revealed positive signal. In conclusion, HPV infection is strongly associated
      with squamous cell carcinoma, but the causal relation of HPV to squamous
      papilloma is inconspicous.

PMID- 9008095
TI  - Overexpression of tissue inhibitors of metalloproteinase-1 and -2 in the stroma
      of gastric cancer.
AB  - The fundamental event of cancer invasion and metastasis is the complicated
      interaction of cancer cells with host cells, in which event, a number of
      proteases and their inhibitors are involved. Matrix metalloproteinases are the
      potent proteases in degrading the basement membrane and extra cellular matrix and
      are inhibited by specific endogeneous inhibitors, tissue inhibitors of
      metalloproteinases-1(TIMP-1) and TIMP-2. The expression of mRNA for TIMP-1 and -2
      was investigated by Northern blot analysis in specimens taken from 27 patients
      with primary gastric adenocarcinoma; 25 samples from the primary site, six from
      the metastatic lymph nodes and two from the peritoneal fluids. The expression for
      TIMP-1 and -2 was compared in primary gastric cancer tissues, metastatic lymph
      nodes and normal gastric mucosae. TIMP-1 mRNA was overexpressed in 24 (96%) out
      of 25 primary cancer tissues compared with the paired normal mucosae, while TIMP
      2 was in 10 (40%). In six specimens of metastatic lymph nodes, TIMP-1 and -2 were
      overexpressed in 6 (100%) and 4 (67%) specimens, respectively. Of two specimens
      prepared from the peritoneal fluids, all specimens overexpressed TIMP-1 compared
      with the those of primary cancer tissues, while one (50%) specimen overexpressed
      TIMP-2. Immunohistochemical staining was done to investigate the localization of
      TIMP-1 and -2, demonstrating that the immunoreactivity for TIMP-1 and -2 was
      clearly detected in the cytoplasm of the stromal cells. These results suggest
      that both TIMP-1 and -2 are overexpressed by stromal cells in most of primary and
      some metastatic gastric cancer tissues and that TIMP-1 and TIMP-2, produced by
      stromal cells, may play an important role in inhibiting the proteolytic activity
      of matrix metalloproteinases originated from cancer cells, in gastric cancer.

PMID- 9008096
TI  - Primary malignant lymphomas of the stomach. Pathological and clinical analyses of
      38 resected cases.
AB  - The stomach is the most frequent site of extranodal lymphoma and primary gastric
      lymphoma might be distinguished from the nodal lymphoma by its different
      pathogenesis and prognosis. Based on the Isaacson's classification, clinico
      pathologic reviews of 38 resected primary gastric lymphomas were done.
      Immunohistochemical stainings for PCNA, B and T cell markers, bcl-2 and p53 were
      performed. Eighteen were of low grade and 20 were of high grade. There were
      significant differences between low and high graders in the aspect of the size,
      depth of lesion, gross type, immunophenotype, staining intensity for PCNA,
      expressions of bcl-2 and p53. The overall 2-year survival rate was 85.3%. Factors
      with prognostic significance on survival by univariate analyses included
      immunophenotype, histologic grading and PCNA staining pattern. After multivariate
      analyses, immunophenotype proved to be a significant factor. We think that the
      histologic grading by Isaacson's classification and the immunohistochemical
      stainings performed were useful in pathologic and/or clinical aspects. The
      excellent survival rate in this study was partly due to the selection of
      resectable cases. However, earlier diagnosis and appropriate treatment might have
      contributed to the improved prognosis of gastric lymphoma in recent years.

PMID- 9008097
TI  - Interstitial mononuclear cell infiltrates in chronic rejection of the kidney and
      correlation with peripheral blood.
AB  - To investigate the characteristics of interstitial inflammatory cells and
      possible involvement of nudelta T cells, 16 renal allograft biopsies showing
      chronic rejection were stained by immunohistochemical method and correlated with
      the data of peripheral blood evaluated by flow cytometry. For immunophenotyping,
      fresh frozen sections were stained with monoclonal antibodies against CD3, CD4,
      CD8, CD68, CD56, TCRdelta1 and HLA DR. Paraffin embedded tissue was stained with
      CD45RO, CD20-Cy and CD68. Nine cases of nonspecific tubulointerstitial change and
      4 cases of nonallograft tubulointerstitial nephritis were used as a control.
      Inflammatory infiltration was present in all cases studied. T cells predominated
      in the interstitium of chronic rejection and were followed by macrophages and B
      cells. The degree of interstitial infiltration of frozen section was not
      accordant with that of paraffin sections. Allografts with nonspecific
      tubulointerstitial changes or tubulointerstitial nephritis of native kidneys
      showed similar distribution pattern in terms of type and degree. However, the
      degree of infiltrate did not give any statistical significance among groups. The
      CD4/CD8 ratios in interstitial infiltrates were less than 1.0 in 6 cases and was
      not accordant with those of peripheral blood. Proportion of nudelta T cells
      increased over 10% in 2 cases in tissue and in 3 cases in peripheral blood. In 3
      cases of chronic rejection in which both tissue and blood results were available,
      there was no concordance of CD4/CD8 or nudeltaT/CD3 between them. Tubular
      expression of HLA DR was, however, present only in 4 cases of chronic rejection.
      In conclusion, T lymphocytes were predominant regardless of diagnosis or disease
      activity. T lymphocyte subset did not give any suggestion as to the diagnosis or
      disease activity in chronic rejection. Furthermore nudelta T cells had only
      limited value. Lymphocytic subsets in peripheral blood would not be predictors of
      tissue destruction in chronic rejection.

PMID- 9008099
TI  - Menstrual and reproductive factors related to the risk of breast cancer in Korea.
      Ovarian hormone effect on breast cancer.
AB  - To support the ovarian hormone hypothesis in the etiology of breast cancer, a
      hospital-based case-control study with community controls was conducted to
      evaluate the relationship of intervals among menstrual and reproductive events to
      the risk of breast cancer in Korea. The cases were 190 breast cancer patients,
      who had been histologically diagnosed at Seoul National University Hospital from
      Jan. 1, 1993 to Jun. 30, 1994. Included were cancer-free women, who had
      undertaken the Gynecological examination at the same hospital (n=190). Women
      recruited for a survey of diabetes prevalence in Yonchon County, adjacent to
      Seoul City, were taken as a community control group (n=190). Information on
      menstrual and reproductive factors with other life-styles was collected through a
      direct interview by the well-trained interviewers. The adjusted odds ratios and
      the 95% confidence intervals were based on the unconditional logistic regression
      model. Likelihood ratio test for trend was applied for the ordinal variables.
      Early age at menarche, late age at natural menopause, late age at first full term
      pregnancy, and fewer number of full term pregnancies are independently associated
      with the high risk of breast cancer in Korea. Moreover, the interval between the
      age at menarche and the age at natural menopause of community controls (29.9+/
      6.15 years) was significantly shortened compared to breast cancer cases (34.9+/
      4.42 years). Particularly noteworthy was that intervals between the age at
      menarche and the age at first full term pregnancy of both control groups (9.0+/
      3.72 years for hospital controls; 7.2+/-4.04 years for community controls) were
      significantly shortened compared to breast cancer cases (11.0+/-4.51 years).
      These findings support the hypothesis that the longer exposure to ovarian
      hormones during the reproductive years, the higher the risk of breast cancer.

PMID- 9008098
TI  - Effects of mixed leukocyte reaction, hydrocortisone and cyclosporine on
      expression of leukocyte adhesion molecules by endothelial and mesangial cells.
AB  - We investigated the effects of mixed leukocyte reaction (MLR), hydrocortisone
      (HC) and cyclosporine A (CsA) on the expression of leukocyte adhesion molecules
      on the mesangial (MC) and endothelial cells (EnC). Cell surface enzyme
      immunoassay showed that INFnu, IL-1beta, or TNF alpha stimulated expression of
      ICAM-1, or VCAM-1 on MC after 24 hours. Flow cytometric analysis demonstrated
      that MLR supernatant induced a marked increase in mean fluorescence of or % of
      cells highly expressing intercellular adhesion molecule(ICAM)-1 or vascular cell
      adhesion molecule (VCAM)-1 on both cells after 24 hours (p<0.001). HC
      treatment(300 ng/ml) during MLR effectively inhibited MLR-induced upregulation of
      ICAM-1 and VCAM-1 on both cells (p<0.005). When MLR supernatant with HC was added
      to adhesion molecule assay, there was no inhibitory effect of HC on VCAM-1. CsA
      treatment (500 ng/ml) during MLR caused a modest decrease in upregulation of VCAM
      1 on EnC (p<0.05), but had no effects on ICAM-1 on both cells. CsA directly
      decreased expression of VCAM-1 on MC. In conclusion, alloreactive lymphocytes and
      monocytes upregulate the expression of VCAM-1 and ICAM-1 on target cells probably
      by the mediation of cytokines. HC effectively prevents MLR-induced upregulation
      of VCAM-1 and ICAM-1. CsA does not increase the expression of VCAM-1 and ICAM-1.

PMID- 9008100
TI  - Experimentally induced Chiari-like malformation with myeloschisis in chick
      embryos.
AB  - Though several pathogenetic theories concerning the frequent association of
      Chiari malformation and hydrocephalus with myeloschisis have been suggested, none
      of them explains all the aspects of the disorder. To investigate whether
      myeloschisis is the direct cause of Chiari malformation and hydrocephalus or
      these conditions are the results of another basic event, we observed the
      morphological changes of the posterior cranial fossa and its components in the
      chick embryos with surgically induced myeloschisis. To make myeloschistic
      lesions, we opened the neural tube for a length of 9-11 somites in Hamburger and
      Hamilton stage 16-19 chick embryos. They were divided into cervicothoracic (C-T)
      and lumbosacral(L-S) groups according to the area of incision. The embryos were
      re-incubated until postoperative day 11. In the control group, embryos were
      incubated with the eggshell window open as their experimental counterparts. The
      survival rates of each group were as follows; 11% (9 survivors/85 operated
      embryos), 8% (7/83), and 17% (10/60) in the C-T, L-S and control groups,
      respectively. Myeloschisis positive rates were 100% in the operated groups and 0%
      in the control group. The heads of embryos were sectioned along the sagittal
      plane to observe the morphological changes in the posterior cranial fossa and its
      components. Of the survivors, five in the C-T group, two in the L-S group and six
      in the control group were available for light microscopic inspection. In the
      majority of embryos with myeloschisis, without difference between the C-T and L-S
      groups, the fourth ventricles were smaller than those of the control group and
      the subarachnoid spaces in the posterior cranial fossa were also narrower. In
      embryos with severe changes, the cerebellum displaced downward comparing with
      that of the control embryos. No evidence of hydrocephalus was present Though not
      always typical, morphological changes similar to Chiari malformation were
      observed in chick embryos with surgically induced myeloschisis. It suggests a
      strong direct causal relationship between the two conditions and supports the
      theories of derangements in cerebrospinal fluid dynamics rather than those of
      primary mesenchymal or neural origin as a pathogenetic mechanism of Chiari
      malformation.

PMID- 9008101
TI  - Expression of androgen receptors in astrocytoma.
AB  - Thirty-two cases of surgically removed astrocytoma were evaluated for the
      expression of androgen receptors(ARs) immunohistochemically and the relationships
      between androgen receptors, DNA ploidy pattern, and survival of patients were
      studied. The cases included 18 grade I/II astrocytomas, 4 anaplastic
      astrocytomas, and 10 glioblastoma multiforme(GBM). Positive AR was present in 12
      out of 32 cases(38%), which consisted of 5 cases in grade I/II(28%), 3 cases in
      anaplastic astrocytoma(75%), and 4 cases in GBM(40%). For both low and high grade
      astrocytomas, sex and ploidy pattern were not correlated with expression of the
      androgen receptors. Androgen receptor expression did not significantly affect the
      survival time. This study confirms previous reports of a low incidence of
      androgen receptors in astrocytomas. In addition, it shows that expression of
      androgen receptors is not correlated with DNA ploidy pattern and survival of
      patients in astrocytoma.

PMID- 9008102
TI  - Lipoma of the parotid gland.
AB  - We report two cases of lipoma of the parotid gland which present as a non-tender,
      freely movable and intraparotid mass. Lipomas are common soft tissue neoplasms
      but found very rarely in the parotid gland, and so are often not considered in
      the initial differential diagnosis of parotid gland tumor. We believe that these
      tumors are cured by simple excision, and thus superficial parotidectomy is enough
      for treatment.

PMID- 9008103
TI  - Tuberous sclerosis and polycystic kidney disease. A case report.
AB  - Polycystic kidney disease is a relatively uncommon finding of tuberous sclerosis.
      Furthermore, the renal insufficiency by the severe polycystic kidney disease is
      extremely rare in tuberous sclerosis. The patient was a 27-year-old man,
      complaining of generalized seizure and progressive abdominal distension. His
      clinical features were chracterized by epilepsy, mental retardation, skin
      abnormalities including adenoma sebaceum, shagreen patch and ash-leaf spots.
      Abdominal computed tomography demonstrated numerous variable sized cysts
      throughout both kidneys. Clinical and laboratory findings revealed chronic renal
      failure due to severe polycystic kidneys. On reviewing the literature, the
      present case is the first report of polycystic kidneys associated with tuberous
      sclerosis in Korea.

PMID- 9008104
TI  - Extracranial vertebral arteriovenous fistula presenting as an osteolytic lesion
      of the axis. Case report.
AB  - Arteriovenous fistulas of the extracranial vertebral artery are rare. The authors
      report a case of a spontaneous arteriovenous fistula of the extracranial
      vertebral artery presenting as an osteolytic lesion at the body of the axis. The
      patient presented with headache and posterior neck pain. The fistula was
      obliterated by an endovascular trapping.

PMID- 9008105
TI  - Congenital quadrigeminal lipoma with osteocartilagenous element. A case report.
AB  - A case of congenital tectal lipoma found incidentally at an autopsy is reported.
      This female fetus was a product of pregnancy termination at 24 weeks of
      gestational age after sonographic detection of hydrocephalus. Autopsy revealed a
      small mass in the periaqueductal portion. The mass was composed of adipose
      tissue, cartilage, and mature bony tissue with hematopoiesis. The resultant
      diagnosis was tectal lipoma with osteocartilagenous element. It is uncertain
      whether the lesion represents a teratoma or hamartoma or mesenchymal metaplasia.
      The osteocartilagenous component suggests the latter.

PMID- 9008106
TI  - Microcystic meningioma. A case report.
AB  - Microcystic meningioma is a distinct morphological variant of meningioma,
      characterized by loose texture and microcysts with formation of large
      extracellular spaces containing edematous fluid. The tumor cells have stellate
      and vacuolated cytoplasm with long cytoplasmic processes. We experienced a case
      of typical microcystic meningioma occurring in the falx cerebri adjacent to the
      left superior parasagittal sinus in a 41-year-old man. The tumor showed the
      typical histologic features with a few nests of meningothelial whorls. The tumor
      cells showed diffuse immunoreactivity for vimentin, epithelial membrane antigen
      (EMA), and S-100 protein. Ultrastructural study confirmed the meningiomatous
      nature of the tumor.

PMID- 9008143
TI  - Bifunctional fusion between nerve growth factor and a transferrin receptor
      antibody.
AB  - The cDNAs encoding the variable regions of the heavy and light chains of a murine
      antibody specific for the human TfR were cloned and a human chimera (gamma1,
      kappa) was produced. A gene fusion was created by joining the 3' end of the
      coding region of the human nerve growth factor (NGF) precursor to the 5' end of
      the heavy chain variable region of the chimeric antibody. When expressed with the
      unmodified light chain in mammalian cells, the protein fusion is properly
      processed, assembled, and secreted. Subsequent purification and characterization
      established the uncompromised bifunctional activities of the protein, relative to
      the unmodified components, as demonstrated by its ability to both bind to the
      human TfR and induce neurite outgrowth in primary sympathetic or spinal ganglia
      and in trkA-transfected pheochromocytoma cells. The ability to generate
      biologically active NGF fused to a TfR targeting antibody, which was previously
      shown to cross the blood-brain barrier, may offer a novel way to deliver NGF and
      other neurotrophic factors to the central nervous system.

PMID- 9008144
TI  - Brain-derived neurotrophic factor spares choline acetyltransferase mRNA following
      axotomy of motor neurons in vivo.
AB  - Choline acetyltransferase (ChAT) is a functional and specific marker gene for
      neurons such as primary motor neurons that synthesize and release acetylcholine
      as a neurotransmitter. In adult mammals, transection of the peripheral nerve
      results in a loss of immunoreactivity for ChAT in the injured motor neurons
      without affecting their cell number. Using a quantitative RNase protection assay,
      we have investigated dynamic changes in ChAT mRNA levels following axotomy of
      motor neurons in the brainstem of adult rats. One week after transection of the
      left hypoglossal nerve, levels of ChAT mRNA in the ipsilateral side of the
      hypoglossal motor nucleus decreased dramatically to around 10% when compared to
      the uninjured contralateral side. When cut axons were chronically exposed to
      brain-derived neurotrophic factor (BDNF) for 1 week, ChAT mRNA levels were
      maintained at 63% of control levels. Thus, BDNF can abrogate the injury-induced
      loss of ChAT mRNA in mature motor neurons in vivo. In contrast, neither
      neurotrophin 4/5 nor nerve growth factor could prevent the decrease in message.
      This effect of BDNF on ChAT mRNA levels following peripheral injury to motor
      neurons demonstrates the existence of regulatory pathways responsive to
      neurotrophic factors that can "rescue" or "protect" cholinergic gene expression.

PMID- 9008145
TI  - Regulatory volume decrease and associated osmolyte fluxes in cerebellar granule
      neurons are calcium independent.
AB  - To investigate a possible role for Ca as a transduction signal for regulatory
      volume decrease (RVD), the effects of external Ca removal, Ca channel blockers
      (Cd, Co, La, Gd, verapamil, diltiazem, dihydropyridines) and inhibitors of
      endoplasmic reticulum Ca release (dantrolene, ryanodine, TMB-8) were examined on
      RVD and on the swelling-activated efflux of two main osmolytes: Cl (traced by
      125I) and [3H]taurine. Omission of Ca plus EGTA did not affect RVD or osmolyte
      release but when BAPTA was the chelator, RVD decreased 20%, 125I fluxes were
      unaffected and taurine stimulated efflux decreased (20%) while the basal efflux
      slightly increased (<10%). Verapamil, diltiazem, Co, Cd, La and Gd did not affect
      RVD or osmolyte fluxes. Nimodipine and nitrendipine (25-50 microM) markedly
      decreased RVD and osmolyte fluxes (>90%) through a mechanism independent of
      extracellular Ca. Swelling elicited an increase in cytosolic Ca measured by fura
      2, which was notably variable ranging 50-350 nM. However, RVD and osmolyte fluxes
      were not affected by the blockers of endogenous Ca release dantrolene, ryanodine
      and TMB-8 or by the permeable Ca chelator BAPTA-AM, even when the cytosolic Ca
      increase was abolished by the chelator. These results indicate that 1) RVD and
      osmolyte fluxes are independent of extracellular Ca 2) RVD, osmolyte release and
      cytosolic Ca raise are only coincident events. Consequently, Ca is unlikely to be
      a transducing signal for RVD in neurons.

PMID- 9008146
TI  - Inhibition of nuclear factor kappa B (NFkappaB) activity induces nerve growth
      factor-resistant apoptosis in PC12 cells.
AB  - The mechanism(s) underlying nerve growth factor (NGF)-mediated rescue of neurons
      from apoptosis is poorly understood, although it is well established that the
      high-affinity NGF receptor (TrkA) plays a pivotal role in mediating NGF effects.
      The report that the low-affinity NGF receptor (p75NGFR) can induce apoptosis
      prompted us to analyze the role played by a putative p75NGFR-associated signal
      transduction element, the transcription factor nuclear factor kappa B (NFkappaB),
      in the modulation of apoptosis in PC12 cells. Here, we report that inhibition of
      NFkappaB function results in apoptosis of rat PC12 cells, a neuroblast-like cell
      line model of NGF-responsive neural tissues. Furthermore, NGF did not protect
      PC12 cells from cell death induced by the inhibition of NFkappaB. These results
      indicate that NFkappaB function is essential to maintain PC12 cell survival and
      to permit NGF-mediated rescue, consistent with the idea that signaling elements
      potentially associated with both TrkA- and p75NGFR are involved in the regulation
      of apoptosis.

PMID- 9008147
TI  - Characterization of microwell cultures of dissociated brain tissue for studies of
      cell-cell interactions.
AB  - Microwell cultures of dissociated tissue from prenatal rat hippocampus and
      cerebral cortex as well as from early postnatal cerebellum were used for
      quantification of neuronal aggregation, process extension, and fasciculation. It
      was shown that the cells in culture from these different brain regions developed
      differently with regard to both architecture and rate of differentiation. The
      effect of a polyclonal antibody against the neural cell adhesion molecule (NCAM),
      the excitatory amino acid receptor agonist N-methyl-D-aspartate (NMDA), and the
      neurotoxin acrylamide on aggregation and fiber formation was investigated.
      Exposure to the NCAM antibody led to formation of fewer but larger aggregates and
      stimulated the morphological development of the cultures. Acrylamide affected
      aggregate formation, leading to smaller but more numerous aggregates, and it
      inhibited process extension and fasciculation. Treatment with NMDA affected
      process formation and led to formation of more numerous but smaller aggregates.
      Some of these effects were strongly tissue-dependent. Thus, large differences
      were seen regarding the effect of the NCAM antibody on aggregation and process
      extension in cultures from the different brain areas. The culture systems appear
      to represent convenient and reliable screening tools to study the influence of
      putative morphoregulatory substances on cell-cell interactions during early
      neuronal development.

PMID- 9008148
TI  - Regeneration of neurosecretory axons into various types of intrahypothalamic
      graft is promoted by the absence of the blood-brain barrier: a neurophysin
      immunohistochemical and horseradish peroxidase-histochemical study.
AB  - In order to test the hypothesis that neurosecretory axon regeneration occurs only
      in the presence of specific vascular, perivascular, and glial microenvironments,
      isografts of neural lobe and optic nerve and autografts of sciatic nerve were
      transplanted into the hypothalamo-neurohypophysial tract at the lateral
      retrochiasmatic area of adult male rats. The integrity of the blood-brain barrier
      (BBB) to intravenously administered horseradish peroxidase (HRP), the
      regenerative process of neurosecretory axons, and functional recovery from lesion
      induced diabetes insipidus were analyzed at 18 hr, 36 hr, 10 days, 30 days, and
      80 days postsurgery. Neurophysin-positive axons invaded all grafts, as well as
      perivascular spaces of the adjacent hypothalamus. Wherever neurosecretory axon
      regeneration occurred, the BBB was breached. Reestablishment of the BBB was
      paralleled by a decrease in both density and staining intensity of regenerated
      neurophysin-positive axons. These observations illustrate that neurosecretory
      axon regeneration is tributary of the absence of BBB. It is speculated that blood
      borne factors, provided when the BBB is breached, initiate and sustain
      neurosecretory axon regeneration. In addition, products of glial elements may
      enhance or complement the above stimulatory processes.

PMID- 9008149
TI  - Anabolic steroids induce injury and apoptosis of differentiated skeletal muscle.
AB  - Apoptosis is an active form of cellular death, or suicide, which plays an
      important physiologic role during organ development and in cellular turnover in
      differentiated tissues. Apoptosis has also been demonstrated to occur in several
      organs in response to hypoxic/ischemic, oxidative, or drug-induced injury and is
      thus involved in disease pathogenesis. However, it is generally assumed that
      apoptosis does not occur in differentiated skeletal muscle. Apoptosis has been
      demonstrated in differentiated myocardial muscle, neonatal skeletal muscle, and
      skeletal myoblasts in response to injury. We therefore studied differentiated
      murine C2 skeletal muscle cells that have been injured by supraphysiologic doses
      (>10 microM) of an anabolic steroid, stanozolol. Stanozolol-injured muscle cells
      exhibited pathologic features suggestive of apoptosis: cytoplasmic shrinkage and
      chromatin condensation. Muscle cells also showed positive in situ nick-end
      labeling of nuclear chromatin, indicating DNA strand breakage. Staining with the
      DNA-binding dye 33342 (bisbenzimide) also showed chromatin changes characteristic
      of apoptotic nuclei. Total protein levels measured at 4 and 24 hr post-stanozolol
      injury was not significantly decreased, indicating absence of cell lysis.
      Cellular ATP levels (nmol ATP/mg protein) of stanozolol-injured muscle cells,
      measured 4 and 24 hr postinjury, also did not change significantly. In contrast,
      necrotic muscle cells, injured by the calcium ionophore A23187 (2 microM), showed
      a progressive decline in total protein and ATP levels. This study supports two
      other histologic studies that showed evidence of apoptosis in differentiated
      skeletal muscle fibers. Our data further suggest that during the early stages of
      apoptosis, but not necrosis, cellular energy metabolism is preserved.

PMID- 9008150
TI  - High-dose anabolic androgenic steroids modulate concentrations of nerve growth
      factor and expression of its low affinity receptor (p75-NGFr) in male rat brain.
AB  - The effects of treatment with a high dose of nandrolone or testosterone on nerve
      growth factor (NGF) levels and NGF low-affinity receptor (p75-NGFr) distribution
      in the brain were analyzed. Nandrolone, subcutaneously injected in rats for
      several weeks, caused an increase of NGF levels in the hippocampus and septum and
      a decrease in the hypothalamus. The number of p75-NGFr-immunoreactive neurons and
      the p75-NGFr expression levels were reduced in the septum and vertical and
      horizontal Broca's bands. Testosterone injections caused an increase of NGF
      levels in the hippocampus, septum, and occipital cortex and induced an
      upregulation of p75-NGFr in the forebrain NGF target regions. This testosterone
      effect suggests that nandrolone and testosterone affect brain NGF target cells by
      a different mechanism(s). Nandrolone may interfere with NGF transport and/or
      utilization by forebrain neurons, causing an altered p75-NGFr expression and NGF
      accumulation as a consequence. Since NGF is known to maintain forebrain neurons
      and to regulate neurobehavioral functions, including memory, learning, and
      defensive behavior, it is possible to hypothesize that this neurotrophin may play
      a role in the mechanism of action of anabolic androgenic steroids (AAS) in the
      brain and be associated with endocrine and behavioral dysfunctions occurring due
      to AAS abuse.

PMID- 9008151
TI  - Leukemia inhibitory factor enhances the regeneration of transected rat sciatic
      nerve and the function of reinnervated muscle.
AB  - The cytokine leukemia inhibitory factor (LIF) favors the survival and growth of
      axons in vitro and in vivo. Fibronectin has been shown to enhance nerve
      regeneration when added in combination with various growth factors including LIF.
      The goal of this study was to evaluate the effect of LIF plus fibronectin on the
      regeneration of transected nerve and functional recovery of reinnervated skeletal
      muscle, in one experimental model of peripheral nerve repair, at two recovery
      times. The rat sciatic nerve was cut at mid-thigh level and a silicone cuff
      containing either saline (control), LIF, or LIF plus fibronectin (L+F) was used
      to bridge the proximal and distal nerve stumps leaving a 1 cm gap between them.
      Rats were then explored at 6 or 12 weeks following the initial surgery.
      Regenerating nerves were assessed by measuring the diameter of myelinated axons,
      conduction velocity, and number of myelinated fibers. Muscle reinnervation was
      assessed by measuring muscle mass, force of contraction, and histologically for
      changes in muscle fiber type (type I and type II). In this report we demonstrate
      that at 6 weeks there were significant increases in 1) nerve conduction velocity,
      2) myelinated axon diameter, and 3) number of myelinated axons over that of
      control (saline-treated) animals. Both LIF groups demonstrated a shift in type II
      muscle fiber area compared to saline-treated controls, with the L+F group having
      a significant increase in muscle mass. At 12 weeks there was an improved recovery
      over and above that demonstrated at 6 weeks. Muscle mass was 65% and 42% greater
      than control for LIF and L+F, respectively. Force of contraction, conduction
      velocity, myelinated fiber number, and diameter were also significantly greater
      for both LIF- and L+F-treated rats than saline-treated rats. These results
      demonstrate that LIF significantly improves the regeneration of damaged
      peripheral nerves and the preservation of muscle viability, resulting in greatly
      enhanced recovery of skeletal muscle function.

PMID- 9008152
TI  - beta-Amyloid peptide induced cytoskeletal reorganization in cultured astrocytes.
AB  - The effects of beta-amyloid (25-35) (betaA) on cultured astrocytes from rat
      cortex were studied and compared with those of a scrambled peptide and with
      untreated cultures. Single addition (from 5 to 200 microg/ml) of betaA peptide
      induced a marked morphological change in astrocytes, changing their flat
      polygonal shape into stellate process-bearing morphology. The changes induced by
      betaA were concentration and time-dependent. The addition of the scrambled
      peptide did not alter cell viability in comparison with untreated astrocyte
      cultures. However, cell viability was dose-dependently decreased by betaA. A
      subpopulation of betaA-treated astrocytes showed an increase in glial fibrillary
      acidic protein (GFAP) and Vimentin (Vim) immunostaining while other reactive
      astrocyte markers such as S100beta, MAP2, and ApoE remained unaltered or
      undetectable. The morphological changes in betaA-treated astrocytes appeared to
      be mainly due to a cytoskeletal reorganization, since the total amounts of GFAP
      and Vim proteins were not essentially modified. These results strongly suggest
      that astrocytes are another cellular target of the effects of betaA and this may
      be relevant to understanding the neuropathology of Alzheimer's disease.

PMID- 9008153
TI  - Visualisation of nitric oxide released by nerve stimulation.
AB  - We have visualised nitric oxide (NO) released from the electrically stimulated
      myenteric plexus and hypogastric nerve. NO was visualised by a reaction with
      luminol and hydrogen peroxide to generate photons which were counted using a
      microscope coupled to a photon counting camera. Electrical stimulation of the
      tissues induced an increase in photon counts which was frequency-dependent and
      prevented by inhibition of the NO synthase or by tetrodotoxin. The light emitted
      during nerve stimulation was not only observed at the nerve terminals but also at
      the axon and soma. Our results indicate that NO released from the whole nerve
      cell may affect target cells surrounding all parts of the nitrergic neuron. Thus,
      NO functions as a unique mechanism of synaptic and non-synaptic communication in
      the nervous system.

PMID- 9008155
TI  - The origins of V(D)J recombination.

PMID- 9008154
TI  - Mutator specificity and disease: looking over the FENce.

PMID- 9008156
TI  - Transcriptional checkpoints determining the fate of male germ cells.

PMID- 9008157
TI  - Phosphorylation of residue 131 of HIV-1 matrix is not required for macrophage
      infection.

PMID- 9008158
TI  - Direct binding of FtsZ to ZipA, an essential component of the septal ring
      structure that mediates cell division in E. coli.
AB  - FtsZ is a soluble, tubulin-like GTPase that forms a membrane-associated ring at
      the division site of bacterial cells. While this ring is thought to drive cell
      constriction, it is not well understood how it is assembled or how it affects
      cell wall invagination. Here we report that FtsZ binds directly to a novel
      integral inner membrane protein in E. coli that we call ZipA. We present genetic
      and morphological evidence indicating that this interaction is required for cell
      division, and show that a fluorescent ZipA-Gfp fusion protein is located in a
      ring structure at the division site, both before and during cell wall
      invagination. ZipA is an essential component of the division machinery, and, by
      binding to both FtsZ and the cytoplasmic membrane, is likely to be directly
      involved in the assembly and/or function of the FtsZ ring.

PMID- 9008159
TI  - The E. coli signal recognition particle is required for the insertion of a subset
      of inner membrane proteins.
AB  - E. coli homologs of the signal recognition particle (SRP) and its receptor are
      essential for viability, but their role in protein export is unclear. To
      elucidate their function, we devised a genome-wide screen to identify genes that
      encode SRP substrates. Inhibition of the SRP pathway sharply blocked the membrane
      insertion of several polytopic inner membrane proteins (IMPs) that were predicted
      to be SRP substrates, but had a smaller effect on the insertion of other IMPs and
      no significant effect on preprotein translocation. Our results suggest that
      whereas most E. coli preproteins and some IMPs can utilize SRP-independent
      targeting pathways effectively, the structural features of a subset of IMPs have
      required the conservation of an SRP-based targeting machinery.

PMID- 9008160
TI  - p62(dok): a constitutively tyrosine-phosphorylated, GAP-associated protein in
      chronic myelogenous leukemia progenitor cells.
AB  - Characteristic of chronic myelogenous leukemia (CML) is the presence of the
      chimeric p210(bcr-abl) protein possessing elevated protein tyrosine kinase
      activity relative to normal c-abl tyrosine kinase. Hematopoietic progenitors
      isolated from CML patients in the chronic phase contain a constitutively tyrosine
      phosphorylated protein that migrates at 62 kDa by SDS-PAGE and associates with
      the p120 ras GTPase-activating protein (GAP). We have purified p62(dok) from a
      hematopoietic cell line expressing p210(bcr-abl). p62(dok) is a novel protein
      with features of a signaling molecule. Association of p62(dok) with GAP
      correlates with its tyrosine phosphorylation. p62(dok) is rapidly tyrosine
      phosphorylated upon activation of the c-Kit receptor, implicating it as a
      component of a signal transduction pathway downstream of receptor tyrosine
      kinases.

PMID- 9008161
TI  - Identification of the Abl- and rasGAP-associated 62 kDa protein as a docking
      protein, Dok.
AB  - A 62 kDa protein is highly phosphorylated in many cells containing activated
      tyrosine kinases. This protein, characterized mainly by its avid association with
      rasGAP, has proved elusive. Anti-phosphotyrosine antibody was used to purify p62.
      From peptide sequence, molecular cloning revealed a cDNA encoding a novel
      protein, p62dok, with little homology to others but with a prominent set of
      tyrosines and nearby sequences suggestive of SH2 binding sites. In cells, v-Abl
      tyrosine kinase binds and strongly phosphorylates p62dok, which then binds
      rasGAP. A monoclonal antibody, 2C4, to the rasGAP-associated p62 reacts with
      p62dok. Thus, p62dok appears to be the long-sought major substrate of many
      tyrosine kinases.

PMID- 9008162
TI  - Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK
      pathway.
AB  - Both NF-kappaB and c-Jun are activated by cytokines such as TNF-alpha and by
      stresses such as UV irradiation. A key step in the activation of NF-kappaB is the
      phosphorylation of its inhibitor, IkappaB alpha, by a ubiquitination-inducible
      multiprotein kinase complex (IkappaB alpha kinase). A central kinase in the c-Jun
      activation pathway is mitogen-activated protein kinase/ERK kinase kinase-1
      (MEKK1). Here, we show that MEKK1 induces the site-specific phosphorylation of
      IkappaB alpha in vivo and, most strikingly, can directly activate the IkappaB
      alpha kinase complex in vitro. Thus, MEKK1 is a critical component of both the c
      Jun and NF-kappaB stress response pathways. Since the IkappaB alpha kinase
      complex can be independently activated by ubiquitination or MEKK1-dependent
      phosphorylation, it may be an integrator of multiple signal transduction pathways
      leading to the activation of NF-kappaB.

PMID- 9008163
TI  - Intercellular trafficking and protein delivery by a herpesvirus structural
      protein.
AB  - We show that the HSV-1 structural protein VP22 has the remarkable property of
      intercellular transport, which is so efficient that following expression in a
      subpopulation the protein spreads to every cell in a monolayer, where it
      concentrates in the nucleus and binds chromatin. VP22 movement was observed both
      after delivery of DNA by transfection or microinjection and during virus
      infection. Moreover, we demonstrate that VP22 trafficking occurs via a
      nonclassical Golgi-independent mechanism. Sensitivity to cytochalasin D treatment
      suggests that VP22 utilizes a novel trafficking pathway that involves the actin
      cytoskeleton. In addition, we demonstrate intercellular transport of a VP22
      fusion protein after endogenous synthesis or exogenous application, indicating
      that VP22 may have potential in the field of protein delivery.

PMID- 9008164
TI  - The solution structure of the S1 RNA binding domain: a member of an ancient
      nucleic acid-binding fold.
AB  - The S1 domain, originally identified in ribosomal protein S1, is found in a large
      number of RNA-associated proteins. The structure of the S1 RNA-binding domain
      from the E. coli polynucleotide phosphorylase has been determined using NMR
      methods and consists of a five-stranded antiparallel beta barrel. Conserved
      residues on one face of the barrel and adjacent loops form the putative RNA
      binding site. The structure of the S1 domain is very similar to that of cold
      shock protein, suggesting that they are both derived from an ancient nucleic acid
      binding protein. Enhanced sequence searches reveal hitherto unidentified S1
      domains in RNase E, RNase II, NusA, EMB-5, and other proteins.

PMID- 9008165
TI  - Characterization of the yeast transcriptome.
AB  - We have analyzed the set of genes expressed from the yeast genome, herein called
      the transcriptome, using serial analysis of gene expression. Analysis of 60,633
      transcripts revealed 4,665 genes, with expression levels ranging from 0.3 to over
      200 transcripts per cell. Of these genes, 1981 had known functions, while 2684
      were previously uncharacterized. The integration of positional information with
      gene expression data allowed for the generation of chromosomal expression maps
      identifying physical regions of transcriptional activity and identified genes
      that had not been predicted by sequence information alone. These studies provide
      insight into global patterns of gene expression in yeast and demonstrate the
      feasibility of genome-wide expression studies in eukaryotes.

PMID- 9008166
TI  - A novel mutation avoidance mechanism dependent on S. cerevisiae RAD27 is distinct
      from DNA mismatch repair.
AB  - Mutations in the S. cerevisiae RAD27 (also called RTH1 or YKL510) gene result in
      a strong mutator phenotype. In this study we show that the majority of the
      resulting mutations have a structure in which sequences ranging from 5-108 bp
      flanked by direct repeats of 3-12 bp are duplicated. Such mutations have not been
      previously detected at high frequency in the mutation spectra of mutator strains.
      Epistasis analysis indicates that RAD27 does not play a major role in MSH2
      dependent mismatch repair. Mutations in RAD27 cause increased rates of mitotic
      crossing over and are lethal in combination with mutations in RAD51 and RAD52.
      These observations suggest that the majority of replication errors that
      accumulate in rad27 strains are processed by double-strand break repair, while a
      smaller percentage are processed by a mutagenic repair pathway. The duplication
      mutations seen in rad27 mutants occur both in human tumors and as germline
      mutations in inherited human diseases.

PMID- 9008167
TI  - Association of BRCA1 with Rad51 in mitotic and meiotic cells.
AB  - BRCA1 immunostaining reveals discrete, nuclear foci during S phase of the cell
      cycle. Human Rad51, a homolog of bacterial RecA, behaves similarly. The two
      proteins were found to colocalize in vivo and to coimmunoprecipitate. BRCA1
      residues 758-1064 alone formed Rad51-containing complexes in vitro. Rad51 is also
      specifically associated with developing synaptonemal complexes in meiotic cells,
      and BRCA1 and Rad51 were both detected on asynapsed (axial) elements of human
      synaptonemal complexes. These findings suggest a functional interaction between
      BRCA1 and Rad51 in the meiotic and mitotic cell cycles, which, in turn, suggests
      a role for BRCA1 in the control of recombination and of genome integrity.

PMID- 9008202
TI  - Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the
      difference is as clear as black and white.
AB  - Genomic instability has been proposed to be the earliest step in radiation
      induced tumorigenesis. It follows from this hypothesis that individuals highly
      susceptible to induction of tumors by radiation should exhibit enhanced radiation
      induced instability. BALB/c white mice are considerably more sensitive to
      radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary
      mammary epithelial cell cultures from these two strains were examined for the
      "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma
      radiation, as a measure of radiation-induced genomic instability. As expected,
      actively dividing cultures from both strains showed a rapid decline of initial
      asymmetrical aberrations with time postirradiation. However, after 16 population
      doublings, cells from BALB/c mice exhibited a marked increase in the frequency of
      chromatid-type breaks and gaps which remained elevated throughout the time course
      of the experiment (28 doublings). No such effect was observed for the cells of
      C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of
      chromatid-type aberrations in the irradiated population remained at or near those
      of nonirradiated controls. These results demonstrate a correlation between the
      latent expression of chromosomal damage in vitro and susceptibility for mammary
      tumors, and provide further support for the central role of radiation-induced
      instability in the process of tumorigenesis.

PMID- 9008168
TI  - Endostatin: an endogenous inhibitor of angiogenesis and tumor growth.
AB  - We previously identified the angiogenesis inhibitor angiostatin. Using a similar
      strategy, we have identified endostatin, an angiogenesis inhibitor produced by
      hemangioendothelioma. Endostatin is a 20 kDa C-terminal fragment of collagen
      XVIII. Endostatin specifically inhibits endothelial proliferation and potently
      inhibits angiogenesis and tumor growth. By a novel method of sustained release,
      E. coli-derived endostatin was administered as a nonrefolded suspension. Primary
      tumors were regressed to dormant microscopic lesions. Immunohistochemistry
      revealed blocked angiogenesis accompanied by high proliferation balanced by
      apoptosis in tumor cells. There was no toxicity. Together with angiostatin data,
      these findings validate a strategy for identifying endogenous angiogenesis
      inhibitors, suggest a theme of fragments of proteins as angiogenesis inhibitors,
      and demonstrate dormancy therapy.

PMID- 9008203
TI  - Estimating lung cancer mortality from residential radon using data for low
      exposures of miners.
AB  - Some recent estimates of lung cancer risk from exposure to radon progeny in homes
      have been based on models developed from a pooled analysis of 11 cohorts of
      underground miners exposed to radon. While some miners were exposed to over
      10,000 working level months (WLM), mean exposure among exposed miners was 162
      WLM, about 10 times the exposure from lifetime residence in an average house and
      about three times the exposure from lifetime residence at the "action level"
      suggested by the U.S. Environmental Protection Agency. The extrapolation of lung
      cancer risk from the higher exposures in the miners to the generally lower
      exposures in the home is a substantial source of uncertainty in the assessment of
      the risk of indoor radon. Using the pooled data for the miners, analyses of lung
      cancer risk were carried out on data restricted to lower exposures, either <50
      WLM or <100 WLM. In the pooled data, there were 115 lung cancer cases among
      workers with no occupational WLM exposure and 2,674 among exposed miners, with
      353 and 562 lung cancer cases in miners with <50 WLM and <100 WLM, respectively.
      Relative risks (RRs) for categories of WLM based on deciles exhibited a
      statistically significant increasing trend with exposure in each of the
      restricted data sets. In the restricted data, there was little evidence of
      departures from a linear excess relative risk model in cumulative exposure,
      although power to assess alternative exposure-response trends was limited. The
      general patterns of declining excess RR per WLM with attained age, time since
      exposure and exposure rate seen in the unrestricted data were similar to the
      patterns found in the restricted data. Risk models based on the unrestricted data
      for miners provided an excellent fit to the restricted data, suggesting
      substantial internal validity in the projection of risk from miners with high
      exposures to those with low exposures. Estimates of attributable risk for lung
      cancer (10-14%) in the U.S. from residential radon based on models from the
      unrestricted data were similar to estimates based on the data for miners
      receiving low exposures.

PMID- 9008204
TI  - Radon, your home or mine?

PMID- 9008205
TI  - Spectra of X-ray-induced and spontaneous intragenic HPRT mutations in closely
      related human cells differentially expressing the p53 tumor suppressor gene.
AB  - Previous work with two closely related human lymphoblast cell lines demonstrated
      that WTK1 cells are more resistant than TK6 cells to X-ray-induced cytotoxicity,
      but more mutable at both the TK and HPRT loci. It was subsequently determined
      that WTK1 cells overexpress a mutant form of the tumor suppressor gene p53, while
      TK6 cells correctly express wild-type p53. Thus these two cell lines allowed us
      to examine the mutational spectra at the HPRT locus in related human lymphoblast
      cell lines differentially expressing p53. Previously, we isolated sets of X-ray
      induced and spontaneous WTK1 mutants and spontaneous TK6 mutants and analyzed the
      mutational spectra by the combination of multiplex polymerase chain reaction
      (PCR) and Southern blot analysis. Somewhat unexpectedly, we found that even
      though there were approximately four times as many mutants induced by X rays in
      WTK1 cells as in TK6 cells, there was very little difference in the mutational
      spectra. In the present study, to determine if there was a higher frequency of
      intragenic deletions among the X-ray-induced WTK1 mutants, we further examined
      the subsets of mutants that contained HPRT point mutations. cDNA sequence
      analysis was used to define the mutation precisely in 19 X-ray-induced and 25
      spontaneous WTK1 mutants and 25 spontaneous TK6 mutants. While subtle differences
      exist in the spectra of HPRT mutations between these two cell lines, the data
      again suggest that p53 is associated with an increase in the frequency of
      mutations at HPRT without an obvious effect on the types of mutations recovered.

PMID- 9008206
TI  - Ultraviolet B-radiation dose influences the induction of apoptosis and p53 in
      human keratinocytes.
AB  - p53 is a tumor suppressor gene that has been implicated in a number of important
      cellular processes, including DNA repair and apoptosis. Genomic damage in human
      keratinocytes caused by ultraviolet B (UVB) irradiation has been shown to induce
      both apoptosis and p53 expression. We have previously observed that p53
      expression in cultured normal human keratinocytes is predominantly perinuclear;
      however, exposure of cells to UVB radiation induces a major shift of p53
      expression to the nucleus. Using terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end-labeling, internucleosomal DNA ladders and
      flow cytometry, we correlated observed changes in p53 expression with the
      induction of apoptosis at low, intermediate and high doses of UVB radiation. High
      doses of UVB radiation induced cells to undergo apoptosis, whereas UVB radiation
      at low doses did not induce apoptosis but appeared to stimulate repair of the DNA
      damage induced by UVB radiation. Intermediate doses of UVB radiation induced a
      heterogeneous population of cells to undergo either DNA repair or apoptosis. The
      level of UVB radiation dose also influenced the induced cellular localization of
      p53. These observed differences in p53 cellular localization correlated with the
      induction of DNA repair or apoptosis. In cells undergoing apoptosis, p53 protein
      was found within the blebs of the degenerating nuclei. Our data give support to
      increasing evidence that p53 may play a role in both the repair of UV-radiation
      induced DNA damage and the induction of apoptosis, and may function as a central
      control checkpoint in response to UVB-radiation-induced DNA damage.

PMID- 9008207
TI  - Further investigation of the response of human uroepithelium to low doses of
      cobalt-60 gamma radiation.
AB  - Explant cultures of normal human uroepithelium were established, exposed to a
      range of 60Co gamma-ray doses from 0.1-5 Gy and grown for 14 days. Expression of
      Myc, p53 and Bc12 proteins in the epithelial cells which grew from irradiated
      explants was measured in situ using immunocytochemistry. The results show that
      overexpression of Bc12 with low Myc expression correlated with resistance to
      radiation as shown by the extent of growth detected on day 14. Strong staining
      for Myc coupled with low or absent Bc12 expression generally correlated with
      radiosensitivity, although the level of p53 of the culture was critical in these
      cases. None of the proteins on their own correlated with radiation response. What
      appeared to be critical was the balance of cells expressing Bc12 and Myc
      proteins. Building on the results presented in a previous paper which showed a
      division of cultures from patients into those showing monotonic and nonmonotonic
      responses, this study presents results for explant cultures from a greater number
      of patients and attempts to characterize the profile of expression of the above
      proteins in the uroepithelium of these patients. It shows that high Bc12/Myc
      ratios were found in cultures which showed a non-monotonic and resistant dose
      response. Where Myc was the dominant protein in the culture postirradiation, a
      radiosensitive and monotonic response tended to occur. Since the proteins are
      being detected in the distant progeny of irradiated cells, it is likely that
      changes induced by radiation in the cell population are stable. The measurement
      of these two proteins can be made in cultured biopsy material and may therefore
      have predictive value in radiotherapy and radiation protection. Both normal and
      tumor biopsies from bladder mucosa showed similar correlations between Bc12/Myc
      ratios and growth postirradiation.

PMID- 9008208
TI  - An ionizing radiation-sensitive CHO mutant cell line: irs-20. IV. Genetic
      complementation, V(D)J recombination and the scid phenotype.
AB  - The genetic defect responsible for hypersensitivity of Chinese hamster ovary
      (CHO) irs-20 cells to ionizing radiation was found to be recessive in nature and
      could be complemented to produce wild-type radiosensitivity in irs-20/human
      hybrids. The radiosensitivities of six hybrid clones were determined based on
      their colony-forming ability under continuous irradiation at 6 cGy/h. A parallel
      cytogenetic analysis revealed a concordance between the presence or absence of
      human chromosome 8 and the resistant or sensitive phenotype. Confirming evidence
      was obtained using human chromosome 8-specific PCR primers. Positive
      amplification was obtained in hybrids with wild-type radiosensitivity, while no
      amplification was obtained in sensitive hybrids. Complementation analysis between
      radiosensitive CHO irs-20 and murine scid cell lines was carried out to determine
      whether the defects leading to their ionizing radiation hypersensitivity could be
      corrected by genetic complementation in the hybrids. Complementation did not
      occur. A transient V(D)J recombination assay after the introduction of the RAG1
      and RAG2 genes indicated that the V(D)J recombination ability of the CHO irs-20
      cells was about 10% of that for the CHO wild-type cells for signal join formation
      with an 80% joining fidelity and only 3% of the parental level for coding join
      formation. These data show that murine scid and irs-20 mutant hamster cells fall
      into the same complementation group and show similar defects in V(D)J
      recombination.

PMID- 9008209
TI  - The effect of proliferative status and clonogen content on the response of mouse
      jejunal crypts to split-dose irradiation.
AB  - The rate of cell production in hierarchical tissues is affected by the
      differentiation probability after each clonogen division and the frequency with
      which divisions take place. We have modified the latter by a high-fiber diet,
      which caused an increase in the BrdUrd labeling index (LI) in jejunal crypts of
      mice, and have tested for a change in tolerance using the in vivo colony assay.
      Clonogens were counted using the in vivo colony assay of crypt regeneration with
      Poisson correction. The LI was estimated by counting BrdUrd-labeled cells in
      longitudinal sections of complete crypts. Arrest in mitosis induced by injection
      of paclitaxel was used to test for a difference in the rate of crypt cell
      production in mice fed low- and high-fiber diets. Split-dose studies were used to
      test whether the change in proliferative status of the crypts was accompanied by
      changes in either the number of clonogens per crypt or their radiosensitivity, or
      an increased proliferative response to radiation-induced cell killing. We found
      an increase in the crypt LI induced by the high-fiber diet was 15-25% and was
      dependent on the time of day. The data on arrest in mitosis did not demonstrate a
      difference in cell production rates based on diet, possibly because of
      insufficient resolution of the assay. We conclude that the high-fiber diet had no
      effect on radiosensitivity, the number of clonogens per crypt (again, within the
      resolution of the assay) or the "repopulated dose," the dose represented by the
      shift in the dose-response curve for 2.5 days relative to that for 6 h. When the
      number of clonogens at the start of rapid proliferation was different (on account
      of different first doses), the repopulated dose was the same when 5 Gy X rays was
      given first but was higher for the animals on the high-fiber diet when 12 Gy was
      given first. The high-fiber diet caused an increase in the LI in the crypts that
      was not accompanied by any change in radiosensitivity or, within the resolution
      of the assay, numbers of clonogens per crypt. The increased LI also did not
      result in an increase in clonogen repopulation between split (and equal) doses.
      However, in split-dose experiments where the first dose was higher and as a
      consequence the number of clonogens at the start of the proliferative response
      was lower, there was evidence of a higher rate of clonogen production with the
      high-fiber diet than with the low-fiber diet.

PMID- 9008210
TI  - Effects of reoxygenation on repair of potentially lethal radiation damage in
      cultured MG-63 osteosarcoma cells.
AB  - The effects of reoxygenation on repair of potentially lethal radiation damage
      were investigated using MG-63 human osteosarcoma cells in vitro. When
      exponentially growing MG-63 cells were cultured under hypoxic conditions for 24
      h, cells stopped growing and remained at a low density. The hypoxic cells were
      then reoxygenated by exposure to air and irradiated with a single dose of 3 Gy X
      rays. The fraction of the reoxygenated cells surviving after 3 Gy increased by a
      factor of 20.6 when the colony assay was delayed for 24 h. In control cells which
      were cultured under aerobic conditions before receiving a single dose of 3 Gy,
      the surviving fraction increased by a factor of 2.5 when the assay was delayed
      for 24 h. The difference in the magnitude of the repair observed between
      reoxygenated and aerobic cells was less prominent in confluent cells plated at
      high density. The enhanced repair after reoxygenation was due mainly to a
      decrease in the alpha coefficient when the dose-survival curve was fitted to the
      linear-quadratic model, whereas the most significant change in the fit of the
      dose-survival curve for the aerobic cells was a decrease in the beta coefficient.
      The control aerobic cells accumulated at G2/M phase after irradiation, whereas
      the reoxygenated cells did not show such an accumulation. When the hypoxic cells
      were irradiated and then reoxygenated, repair of these cells irradiated under
      hypoxic conditions was also enhanced. This is the first report to show that
      reoxygenation could increase cell survival after tumor irradiation.

PMID- 9008212
TI  - A method for estimating occupational radiation dose to individuals, using weekly
      dosimetry data.
AB  - Statistical analyses of data from epidemiological studies of workers exposed to
      radiation have been based on recorded annual radiation doses. It is usually
      assumed that the annual doses are known exactly, although it is generally
      recognized that the data contain uncertainty due to measurement error and bias.
      We propose the use of a probability distribution to describe an individual's dose
      during a specific period and develop statistical methods for estimating this
      distribution. The methods take into account the "measurement error" that is
      produced by the dosimetry system and the bias that was introduced by policies of
      recording doses below a threshold as zero. The method is applied to a sample of
      dose histories over the period 1945 to 1955 obtained from hard-copy dosimetry
      records at Oak Ridge National Laboratory (ORNL). The result of this evaluation
      raises serious questions about the validity of the historical personnel dosimetry
      data that are currently being used in studies of the effects of low doses in
      nuclear industry workers. In particular, it appears that there was a systematic
      underestimation of doses for ORNL workers. This may result in biased estimates of
      dose-response coefficients and their standard errors.

PMID- 9008211
TI  - Stroma-free human hemoglobin A decreases R3230Ac rat mammary adenocarcinoma blood
      flow and oxygen partial pressure.
AB  - We examined the effect of a nitric oxide (NO) quencher, stroma-free human
      hemoglobin A (HbA0; 0.01, 0.05, 0.1, 0.2 g/kg), on the blood flow measured using
      the Doppler flow technique, tumor oxygen pressure (pO2) and the diameter of the
      arterioles using R3230Ac mammary adenocarcinoma as the tumor model. In female
      Fischer 344 rats with 1-cm-diameter tumors implanted in the lateral aspect of the
      left quadriceps, intravenous infusion of 0.1 and 0.2 g/kg HbA0 decreased both
      central tumor and peripheral tumor blood flow by 20-30% (P < 0.05). Tumor pO2
      decreased 28% with 0.2 g/kg HbA0, from 15 mm Hg (baseline) to 11 mm Hg at 10 min
      (P = 0.02). Although 0.2 g/kg HbA0 increased blood flow 55% in the left
      quadriceps muscle proximal to the implanted tumor (P < 0.05), HbA0 had little
      effect on blood flow in right quadriceps muscle with no tumor implanted, and
      increased right quadriceps pO2, from 21 mm Hg (baseline) to 23 mm Hg at 10 min (P
      = 0.03). HbA0 increased mean arterial pressure 5-10% in a manner that was
      dependent on dose while heart rate concurrently decreased 9-19%. The diameter of
      the arterioles supplying the tumor was rapidly reduced 10% by 0.2 g/kg HbA0 (P =
      0.037) and remained stable through 60 min of observation (P = 0.005). HbA0
      selectively reduces tumor blood flow and tumor pO2 through vasoconstriction of
      the arterioles supplying the tumor. Vascular NO quenching provides an alternative
      to NO synthase inhibition as a means to achieve the goal of selective tumor
      hypoxia.

PMID- 9008213
TI  - The influence of track structure on the understanding of relative biological
      effectiveness for induction of chromosomal exchanges in human lymphocytes.
AB  - A biophysical model has been applied to describe the production of exchange
      chromosomal aberrations (dicentrics) in human lymphocytes by radiations of
      different qualities. The model includes a detailed description of the energy
      deposition pattern in the form of computer-generated tracks. Energy deposition
      events are further converted to DNA double-strand breaks (DSBs). Formation of
      chromosomal exchanges is modeled in competition with repair in a distance
      dependent manner with breaks in proximity being most likely to interact. We
      demonstrate that an assumption of an RBE > 1 for production of DSBs at higher LET
      leads to a significant increase with LET of both the linear and the quadratic
      coefficients of the dose response for exchange formation. The latter is not
      supported experimentally and argues against high RBE values for production of
      DSBs, at least for those breaks involved in chromosomal exchanges. Assuming that
      the RBE for production of DSBs is unity, the calculated dose-response curves
      conformed to experimental data for 60Co gamma rays, 250 kVp X rays and 8.7 MeV
      protons. The linear coefficient for 23.5 MeV 3He ions is underpredicted. The
      model predicts that a quadratic term in the dose response for exchange
      aberrations should be observed at LET values of 20-30 keV/microm. The curvature
      is not observed experimentally, and the contradiction is discussed.

PMID- 9008214
TI  - Biodosimetry of Chernobyl cleanup workers from Estonia and Latvia using the
      glycophorin A in vivo somatic cell mutation assay.
AB  - The reactor accident at Chernobyl in 1986 necessitated a massive environmental
      cleanup that involved over 600,000 workers from all 15 Republics of the former
      Soviet Union. To determine whether the whole-body radiation received by workers
      in the course of these decontamination activities resulted in a detectable
      biological response, over 1,500 blood samples were obtained from cleanup workers
      sent from two Baltic countries, Estonia and Latvia. Here we report the results of
      studies of biodosimetry using the glycophorin A (GPA) locus in vivo somatic cell
      mutation assay applied to 734 blood samples from these workers, to 51 control
      samples from unexposed Baltic populations and to 94 samples from historical U.S.
      controls. The data reveal inconsistent evidence that the protracted radiation
      exposures received by these workers resulted in a significant dose-associated
      increase in GPA locus mutations compared with the controls. Taken together, these
      data suggest that the average radiation exposure to these workers does not
      greatly exceed 10 cGy, the minimum levels at which radiation effects might be
      detectable by the assay. Although the protracted nature of the exposure may have
      reduced the efficiency of induction of GPA locus mutations, it is likely that the
      estimated physical doses for these cleanup worker populations (median reported
      dose 9.5 cGy) were too low to result in radiation damage to erythroid stem cells
      that can be detected reliably by this method.

PMID- 9008215
TI  - Thyroid nodularity and cancer among Chernobyl cleanup workers from Estonia.
AB  - Thyroid examinations, including palpation, ultrasound and, selectively, fine
      needle aspiration biopsy, were conducted on nearly 2,000 Chernobyl cleanup
      workers from Estonia to evaluate the occurrence of thyroid cancer and nodular
      thyroid disease among men with protracted exposure to ionizing radiation. The
      examinations were conducted in four cities in Estonia during March-April 1995, 9
      years after the reactor accident. The study population was selected from a
      predefined cohort of 4,833 cleanup workers from Estonia under surveillance for
      cancer incidence. These men had been sent to Chernobyl between 1986 and 1991 to
      entomb the damaged reactor, remove radioactive debris and perform related cleanup
      activities. A total of 2,997 men were invited for thyroid screening and 1,984
      (66%) were examined. Estimates of radiation dose from external sources were
      obtained from military or other institutional records, and details about service
      dates and types of work performed while at Chernobyl were obtained from a self
      administered questionnaire. Blood samples were collected for assay of chromosomal
      translocations in circulating lymphocytes and loss of expression of the
      glycophorin A (GPA) gene in erythrocytes. The primary outcome measure was the
      presence or absence of thyroid nodules as determined by the ultrasound
      examination. Of the screened workers, 1,247 (63%) were sent to Chernobyl in 1986,
      including 603 (30%) sent in April or May, soon after the accident. Workers served
      at Chernobyl for an average of 3 months. The average age was 32 years at the time
      of arrival at Chernobyl and 40 years at the time of thyroid examination. The mean
      documented radiation dose from external sources was 10.8 cGy. Biological
      indicators of exposure showed low correlations with documented dose, but did not
      indicate that the mean dose for the population was higher than the average
      documented dose. Ultrasound examinations revealed thyroid nodules in 201
      individuals (10.2%). The prevalence of nodules increased with age at examination,
      but no significant associations were observed with recorded dose, date of first
      duty at Chernobyl, duration of service at Chernobyl, building the sarcophagus or
      working on the roof of neighboring buildings or close to the damaged reactor.
      Nodularity showed a nonsignificant (p(1) = 0.10) positive association with the
      proportion of lymphocytes with chromosome translocations, but associations with
      the frequency of variant erythrocytes in the GPA assay were weak and unstable
      (p(1) > or = 0.46). The majority of fine-needle biopsies taken on 77 study
      participants indicated benign nodular disease. However, two cases of papillary
      carcinoma and three benign follicular neoplasms were identified and referred for
      treatment. Both men with thyroid cancer had been sent to Chernobyl in May of
      1986, when the potential for exposure to radioactive iodines was greatest.
      Chernobyl cleanup workers from Estonia did not experience a markedly increased
      risk of nodular thyroid disease associated with exposure to external radiation.
      Possible reasons for the apparent absence of effect include low radiation doses,
      the protracted nature of the exposure, errors in dose measurement, low
      sensitivity of the adult thyroid gland or the insufficient passage of time for a
      radiation effect to be expressed.

PMID- 9008216
TI  - Evaluation of internal alpha-particle radiation exposure and subsequent fertility
      among a cohort of women formerly employed in the radium dial industry.
AB  - This study examined the effect of internal exposure to alpha-particle radiation
      on subsequent fertility among women employed in the radium dial industry prior to
      1930, when appreciable amounts of radium were often ingested through the practice
      of pointing the paint brush with the lips. The analysis was limited to women for
      whom a radium body burden measurement had been obtained and who were married
      prior to age 45 (n = 603). Internal radiation dose to the ovary was calculated
      based on initial intakes of radium-226 and radium-228, average ovarian mass,
      number and energy of alpha particles emitted, fraction of energy absorbed within
      the ovary, effective retention integrals and estimated photon irradiation. Time
      between marriage and pregnancy, number of pregnancies and number of live births
      served as surrogates for fertility. Radiation appeared to have no effect on
      fertility at estimated cumulative ovarian dose equivalents below 5 Sv; above this
      dose, however, statistically significant declines in both number of pregnancies
      and live births were observed. These trends persisted after multivariable
      adjustment for potential confounding variables and after exclusion of subjects
      contributing a potential classification or selection bias to the study.
      Additionally, the high-dose group experienced fewer live births than would have
      been expected based on population rates. There were no differences in time to
      first pregnancy between high- and low-dose groups. These results are consistent
      with earlier studies of gamma-ray exposures and suggest that exposure to high
      doses of radiation from internally deposited radium reduces fertility rather than
      inducing sterility.

PMID- 9008217
TI  - Immunohistochemical localization of transforming growth factor beta and tumor
      necrosis factor alpha in the lungs of fibrosis-prone and "non-fibrosing" mice
      during the latent period and early phase after irradiation.
AB  - To evaluate the possibility that TGF-beta and TNF-alpha are involved in fibrosis
      induced in mouse lung by irradiation, the proportion of cells immunoreactive for
      each was compared in two strains of mice. C3HeB/FeJ mice develop only classical
      pneumonitis during the early phase, whereas C57L/J mice develop small, tightly
      packed areas of inflammation which undergo fibrosis during the latent period, and
      exhibit progressive fibrosis of large regions of intense inflammation during the
      early phase. Very few cells were immunoreactive for an antibody to the latency
      associated peptide (LAP) of TGF-beta during the latent period in C3HeB/FeJ mice,
      and no cells were positive during the early phase. In contrast, between 0.7 and
      10% of cells were positive in C57L/J mice in lesions without fibrosis and in
      lesions in the early stages of fibrosis. Fibroblasts positive for LAP were seen
      only in lesions containing fibrosis. A similar pattern of immunoreactivity was
      seen in C57L/J mice using an antibody which recognizes active TGF-beta, with the
      exception that positive fibroblasts were observed within areas of inflammation
      without fibrosis. Thus the association of active TGF-beta with fibroblasts might
      be a characteristic of the initiation of fibrosis in this model. TNF-alpha was
      detected in macrophages in all classes of lesions, and minor differences between
      the strains did not appear to be biologically meaningful.

PMID- 9008218
TI  - Late response to whole-lung irradiation alone and with whole-body hyperthermia in
      dogs.
AB  - The late effects of whole-lung irradiation with and without whole-body
      hyperthermia were studied in beagle dogs. The reference doses ranged from 18 to
      49.5 Gy given in 1.5-Gy fractions over 6 weeks. Whole-body hyperthermia was given
      in three 2-h treatments to a deep rectal temperature of 42.0 degrees C. Radiation
      was given simultaneously with hyperthermia on those days. Physiological and
      histopathological responses were evaluated. Physiological changes included
      decreases in cardiac output, systemic blood pressure, dynamic compliance and
      serotonin uptake. Early changes included an increase in extravascular water and
      total protein in the lavage. These changes were considered mild, were compensated
      for and occurred only in dogs receiving doses of 40.5 Gy or greater given in 1.5
      Gy fractions over 6 weeks. Histopathological changes were typical of irradiated
      lung and included pleural fibrosis, interstitial fibrosis, fibrotic foci, and
      peribronchial and perivascular fibrosis. There was no enhancement of late injury
      to lung by hyperthermia seen in this study.

PMID- 9008219
TI  - The effect of iodine-based contrast agents on the levels of radiation-induced
      chromosomal aberrations.
AB  - The effects of iodine-based contrast agents on the repair of radiation-induced
      chromosomal damage were investigated employing peripheral blood from a healthy
      male donor. The blood samples were irradiated with 0.5-4.0 Gy 137Cs gamma rays.
      Contrast agents and NaCl solutions of various concentrations were added to the
      blood within the first 15 min or at 60 min after irradiation, and the samples
      were subsequently cultured for 45 h at 37 degrees C. Significantly elevated
      frequencies of chromosomal abnormalities caused by postirradiation treatment with
      hypertonic contrast agents appeared to increase with increasing hypertonicity.
      Elevated aberration frequencies were found to be greatest in the samples treated
      within 15 min of irradiation. The contrast agents had little effect if they were
      added at 60 min after irradiation, probably because the process of chromosome
      rejoining had been completed. Isotonic iodine-based contrast agents did not
      enhance the frequencies of chromosomal aberrations to a significant degree.

PMID- 9008220
TI  - Continuation of the discussion concerning neutron effects at Hiroshima.

PMID- 9008221
TI  - The survival of mouse spermatogonia exposed to alpha particles.

PMID- 9008222
TI  - Ultraviolet A irradiation upregulates type VII collagen expression in human
      dermal fibroblasts.
AB  - Type VII collagen, a major component of skin-anchoring fibrils, is synthesized by
      both fibroblasts and keratinocytes, the two principal cell types in the skin. In
      this study, we examined the effects of ultraviolet A (UVA) irradiation on the
      expression of type VII collagen in human fibroblasts. UVA irradiation (0-15
      J/cm2) caused a dose-dependent increase (5- to 10-fold) in type VII collagen mRNA
      levels as detected by northern blot analysis. The UVA-induced enhancement of type
      VII collagen gene expression correlated with an increase in its protein level by
      immunoblot analysis of proteins secreted into the conditioned medium. The effect
      of UVA was observed at 12 h and reached its maximum by 18 h. Under these
      conditions, however, the expression of fibronectin, a major dermal matrix
      protein, remained unchanged, suggesting that the induction of type VII collagen
      expression was selective. Actinomycin D, a transcription inhibitor, blocked the
      UVA-mediated induction of type VII collagen gene expression, whereas
      cycloheximide, a protein synthesis inhibitor, superinduced the expression of type
      VII collagen, suggesting that de novo protein synthesis was not required for the
      action of UVA. Interestingly, in contrast to the increased type VII collagen
      expression in fibroblasts in response to UVA, a slight decrease in type VII
      collagen mRNA level was observed in the UVA-irradiated keratinocytes, suggesting
      that the effect of UVA on the type VII collagen expression is cell type specific.

PMID- 9008223
TI  - Significantly increased occurrence of HLA-DQB1*0301 allele in patients with
      ocular cicatricial pemphigoid.
AB  - To determine the immunogenetic characteristics of patients with immune-mediated
      subepithelial blistering diseases of mucous membranes, we performed HLA-typing
      for the class II MHC gene DQB1*0301 allele using a direct method. Genomic DNA
      extracted from Caucasian patients was amplified by polymerase chain reaction
      using primer pairs specific for the DQB loci followed by Southern blotting with a
      peroxidase-conjugated sequence-specific oligonucleotide probe. Seventy-six
      percent (16/21) of patients with ocular mucosal disease (with or without oral
      mucosal and skin diseases) carried the DQB1*0301 allele; by contrast, only 33%
      (14/42) of race-, age-, and geography-matched normal individuals carried the
      DQB1*0301 allele (p < 0.005). The relative risk for ocular disease if DQB1*0301
      allele is present is 6.4, similar to the relative risk of 8 for patients with
      ocular but no oral disease (pure ocular cicatricial pemphigoid, p < 0.025). In
      patients with oral mucosal disease (with or without ocular mucosal and skin
      diseases), 68% (15/22) carried the DQB1*0301 allele (p < 0.025). When patients
      with ocular disease were excluded, however, the increased occurrence of the
      DQB1*0301 allele in patients with oral disease was not statistically significant
      (64%, 7/11, p < 0.25). In patients with subepidermal blistering skin disease but
      no oral or ocular disease, there was no increase in the occurrence of the
      DQB1*0301 allele (38%, 5/13, p > 0.5). The significantly increased occurrence of
      the DQB1*0301 allele in patients with ocular mucosal disease may point to a
      distinct immunogenetic factor that predisposes patients to develop an ocular
      scarring process.

PMID- 9008224
TI  - Sunscreens offer the same UVB protection factors for inflammation and
      immunosuppression in the mouse.
AB  - Many studies report that sunscreens effective against UVR-induced inflammation
      afford poor protection against immunosuppression. We have studied the
      relationship between photoprotection of inflammation and immunosuppression with
      monochromatic UVB (Philips TL01 tubes, lambda max = 311 nm) to remove possible
      confounding effects of differences in end point action spectra. Dose-response
      curves for edema and systemic suppression of contact hypersensitivity (CHS) in
      HRA.HRII-c/+/Skh mice showed that suppression of CHS was more sensitive to UVB
      irradiation by a factor of 2. The UVB dose-response curve for murine edema was
      similar to that for human erythema, with threshold doses of 773 mJ x cm(-2) and
      632 mJ x cm(-2), respectively. The protection afforded by two UVB filters, octyl
      dimethyl para-aminobenzoic acid and 2-ethylhexyl-4'-methoxycinnamate, prepared in
      an identical vehicle, each with the same optical density at 311 nm, was tested in
      mice. We applied sunscreen to all exposed skin or to transpore tape above the
      irradiation cages, prior to exposure with 2.8 minimal edema doses. Topical or
      tape application of both sunscreens protected totally against edema but only
      partially against immunosuppression, with no significant difference in protection
      between the two application techniques (p > 0.4). A sunscreen protection factor
      of 4 in vivo was determined for 2-ethylhexyl-4'-methoxycinnamate for both edema
      and immunosuppression. Failure of the sunscreens to protect completely against
      immunosuppression was due to the ability of subedemal doses of UVB to induce
      substantial immunosuppression and not, as previously suggested, to any skin
      interaction.

PMID- 9008225
TI  - The distribution of the desmosomal protein, plakophilin 1, in human skin and skin
      tumors.
AB  - Desmosomes are predominant among the types of plaque-bearing adhering junctions
      found in human skin. These structures contain a set of desmosomal cadherins and
      cytoplasmic plaque proteins, the synthesis of which is differentiation dependent.
      As plakophilin 1, a member of the armadillo gene family, is an important
      accessory desmosomal plaque protein, we raised several monoclonal antibodies
      specific for this protein and applied immunohistochemical and immunoblotting
      procedures to study the distribution of plakophilin 1 in desmosomes in adult and
      fetal skin, psoriatic epidermis, various epithelial skin tumors, and keratinocyte
      sheets grown in culture. In epidermis, the spinous layers were prominently
      immunostained by plakophilin 1 antibodies, whereas the basal cell layer was only
      weakly stained and the stratum corneum was entirely unstained. The staining
      observed in psoriatic epidermis was somewhat heterogeneous. In hair follicles,
      the outer root sheath (ORS) was delineated in its suprabasal cell layers, with
      variable staining in its upper and lower parts. All basal cells of the ORS
      remained unstained, as did upper inner root sheath (IRS) and matrix cells of
      lower bulb. In eccrine sweat glands, the reaction was confined to inner dermal
      ductal cells, with the acini remaining unstained. The desmosomal immunostaining
      observed in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) was
      very heterogeneous: In general, junctions in well-differentiated stratified tumor
      regions were more intensely stained than sections of poorly differentiated and
      invasively growing BCCs and SCCs. Plakophilin 1 was also prominent in the
      desmosomes of keratinocyte sheets grown in culture. The cell type-specific, i.e.,
      differentiation-dependent, distribution of desmosomal plakophilin 1 is discussed
      in relation both to the stratification of the cutaneous epithelia and to tumor
      differentiation and growth.

PMID- 9008226
TI  - Fibronectin suppresses apoptosis in normal human melanocytes through an integrin
      dependent mechanism.
AB  - Recent reports show that components of the extracellular matrix function as cell
      survival factors through the suppression of apoptosis (programmed cell death). In
      this report we show that attachment to fibronectin suppresses apoptosis of normal
      human fetal and neonatal melanocytes in vitro and that prevention of attachment
      to underlying matrix or attachment to poly-L-lysine is a potent inducer of
      apoptosis in melanocytes. A role for the beta1-integrin family in mediating cell
      survival signals was shown by the ability of beta1-blocking antibodies to enhance
      apoptosis in melanocytes attached to fibronectin, and by the ability of anti
      beta1 antibodies immobilized on solid supports to suppress apoptosis in
      melanocytes. Cytochalasin D reversed the effect of fibronectin on the suppression
      of apoptosis in melanocytes, suggesting that an intact cytoskeleton is required
      for transduction of survival signals. A human metastatic melanoma cell line,
      SKMEL28, was resistant to apoptosis when grown in suspension or on poly-L-lysine,
      even after 4 d in culture in the absence of exogenous growth factors. These
      results suggest that fibronectin suppresses apoptosis in normal human melanocytes
      through an integrin-dependent pathway and that significant differences in the
      control of anchorage-dependent regulation of apoptosis exist in melanocytes and
      melanoma cells.

PMID- 9008227
TI  - The comet assay as a repair test for prenatal diagnosis of Xeroderma pigmentosum
      and trichothiodystrophy.
AB  - Xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) are autosomal recessive
      diseases associated with extreme cutaneous photosensitivity, a defect in
      nucleotide excision repair (NER), and genetic complexity. Severe prognosis and
      lack of treatment led families at risk to request genetic counseling. Unscheduled
      DNA synthesis (UDS) is the classic method for diagnosis and requires 4 to 5 wk
      before conclusion. The use of the alkaline comet assay (single cell gel
      electrophoresis assay) is proposed as a simple repair test for earlier prenatal
      diagnosis. Amniotic or chorionic villus cells in two pregnancies at risk for XP
      and one for TTD were examined in comparison with skin fibroblasts of family
      members or with repair-proficient or -deficient control cells. The comet assay
      and the UDS test were performed in parallel. In repair-proficient cells, DNA
      strand breaks due to the incision of UV-induced DNA damage result in increased
      migration of high molecular weight DNA in the comet assay. Fetal cells
      demonstrate repair capacity similar to that of fibroblasts. In incision repair
      deficient XP and TTD cells, after post-UV incubation, migration does not occur
      and comet moments are reduced. Two fetuses belonging to two XP families responded
      normally and were diagnosed as unaffected. Fetal cells in a TTD family had
      reduced comet moments and a low UDS. This fetus was diagnosed and confirmed later
      as affected. Heterozygotes had normal responses with both assays. The comet assay
      offers discrimination similar to that of the UDS assay in identifying NER
      deficient phenotypes. Practical advantages in view of prenatal diagnosis include
      the reduced number of cells required, a 24-h delay in obtaining results, and no
      need for radioactivity.

PMID- 9008228
TI  - Production of POMC, CRH-R1, MC1, and MC2 receptor mRNA and expression of
      tyrosinase gene in relation to hair cycle and dexamethasone treatment in the
      C57BL/6 mouse skin.
AB  - In skin of the C57BL/6 mouse, the production of mRNA transcripts that hybridized
      to the coding region of the MC1 receptor (MC1-R) gene was undetectable in
      telogen, increased during hair growth, and, after reaching the highest values in
      anagen VI, decreased during the anagen-catagen transition phase. This production
      was associated with anagen-dependent expression of the tyrosinase gene and enzyme
      activity. In contrast, the production of 4.5- and 2.0-kb mRNAs hybridizable to
      the coding region of the MC2 receptor (MC2-R) gene was similar throughout the
      entire hair cycle. Previously, dexamethasone was demonstrated to induce premature
      catagen development accompanied by an abrupt termination of melanogenesis. Here
      we demonstrate that topical application of dexamethasone during anagen VI
      decreased the concentration of POMC, MC1-R, and tyrosinase mRNA in the skin. The
      decrease in tyrosinase mRNA concentration was accompanied by a decrease in
      tyrosinase protein concentration and enzyme activity. These results support the
      hypothesis that murine hair growth and attendant melanogenesis can be regulated
      through coordinated changes in local expression of POMC, MC1-R, and tyrosinase
      genes.

PMID- 9008229
TI  - The analysis of tyrosinase-specific mRNA in blood samples of melanoma patients by
      RT-PCR is not a useful test for metastatic tumor progression.
AB  - Reverse transcription (RT) of the tyrosinase mRNA and specific cDNA amplification
      by nested polymerase chain reactin (PCR) have been reported to facilitate the
      early detection of circulating tumor cells in melanoma patients. The significance
      and practical value of this procedure for the diagnosis of tumor dissemination in
      melanoma patients are unclear. In the current study we analyzed peripheral blood
      samples of 65 melanoma patients of different clinical stages for the presence of
      tyrosinase mRNA by RT-PCR using nested oligonucleotide primers specific for
      tyrosinase cDNA. Furthermore, blood samples were evaluated for tumor cell growth
      by cell culture assays in vitro. No tyrosinase mRNA was detectable in blood
      samples of 26 patients with primary melanoma and 16 patients with regional lymph
      node metastases. In five of 13 patients with visceral metastases we found at
      least one blood sample positive for tyrosinase mRNA during a 2-to 4-mo interval.
      Analyses of different blood samples of patients with visceral metastases taken in
      a 2-h interval, furthermore, indicate that tumor cells only transiently persist
      in the peripheral blood. We obtained in vitro proliferating melanoma cells from
      two blood samples derived from different patients with visceral melanoma
      metastases. This demonstrates that viable melanoma cells indeed circulate in the
      peripheral blood with retained proliferative capacity in vitro. The analysis of
      blood samples by RT-PCR for tyrosinase mRNA, however, is not suitable for the
      early detection of tumor progression in melanoma patients.

PMID- 9008230
TI  - Evidence for specific proteolytic cleavage of the N-terminal domain of human
      profilaggrin during epidermal differentiation.
AB  - Profilaggrin is a large phosphoprotein that is expressed in the granular cells of
      epidermis where it is localized in keratohyalin. It consists of multiple copies
      of single filaggrin units plus N- and C-terminal sequences that differ from
      filaggrin. Profilaggrin is dephosphorylated and proteolytically processed during
      terminal differentiation to yield filaggrin, which associates with keratin
      intermediate filaments to form macrofibrils in the lower layers of the stratum
      corneum. The N-terminal sequence of human profilaggrin comprises two distinct
      domains; an acidic A domain of 81 amino acids that binds Ca2+, and a cationic B
      domain of 212 residues. In this report, we further characterize the N-terminal
      domain by immunohistochemistry and immunoblot analysis using anti-peptide
      antibodies raised to the A and B regions. All of these antibodies (n = 4)
      immunostained keratohyalin in the granular layer of human epidermis and also
      showed some reaction with the lower stratum corneum. In immunoblot studies, the
      high molecular weight human profilaggrin reacted with both B domain antibodies
      whereas it showed a weak and variable reaction with A domain antibodies. In
      addition to profilaggrin, a cationic 32-kDa protein was detected with all N
      terminal antibodies. A similar-sized N-terminal peptide was also produced by in
      vitro proteolysis of human profilaggrin with endoproteinase 1 (PEP1), a protease
      involved in processing of mouse profilaggrin, and in cultured rat epidermal
      keratinocytes transfected with a human profilaggrin cDNA construct. Evidence for
      at least one additional cleavage within the N-terminal domain is shown by
      immunoreactivity of smaller (16-20 kDa) acidic and basic proteins with A and B
      domain antibodies, respectively. These results demonstrate that the N-terminal
      domain is an integral part of profilaggrin in keratohyalin but is proteolytically
      cleaved from profilaggrin during the terminal differentiation of keratinocytes to
      yield a 32-kDa peptide.

PMID- 9008231
TI  - Transient expression of epidermal filaggrin in cultured cells causes collapse of
      intermediate filament networks with alteration of cell shape and nuclear
      integrity.
AB  - Filaggrin is an intermediate filament-associated protein (IFAP) that aggregates
      epidermal keratin filaments in vitro and is thought to perform a similar function
      during terminal differentiation in vivo. To test this function in living cells,
      we transiently expressed constructs encoding human filaggrin in both simple
      epithelial cells (COS-7) and rat keratinocytes. Scanning laser confocal
      microscopy showed that filaggrin-positive cells had collapsed keratin and
      vimentin intermediate filament (IF) networks, and that filaggrin partially co
      localized with the IF networks. Filaggrin was also detected diffusely in the
      cytoplasm and nucleus. In contrast, when profilaggrin-like constructs, containing
      five filaggrin domains separated by the linker sequences, were expressed in
      cultured cells, immunoreactive granules formed. This finding is reminiscent of
      the insoluble nature of native profilaggrin that accumulates in keratohyalin
      granules in vivo, suggesting that the linker peptides (present in profilaggrin
      but not filaggrin) are important for granule formation. Cells expressing
      filaggrin also displayed disruption of the nucleus and the nuclear envelope; they
      rounded up and lost attachment to the substratum, in contrast to control cells
      over-expressing beta-galactosidase. This functional test of filaggrin in living
      cells supports its role in the reorganization and packing of keratin IF in
      epidermal differentiation. Moreover, the observed effects on cell morphology and
      nuclear integrity suggest that filaggrin may contribute to the form of apoptosis
      associated with terminal differentiation in epidermis.

PMID- 9008232
TI  - Identification of aberrantly regulated genes in diseased skin using the cDNA
      differential display technique.
AB  - It is hypothesized that psoriasis may be caused by aberrant gene expression. In
      an effort to identify and clone psoriasis-specific genes, we compared gene
      expression in normal, tape-stripped (wounded), and psoriatic skin using the cDNA
      differential display technique. Four genes not previously described in psoriasis-
      connexin 26, a gap junction protein; squamous cell carcinoma antigen-1 (SCCA1), a
      serine protease inhibitor; and mitochondrial NAD subunits 5 and 6--were
      identified as having very high expression levels in psoriatic skin. In situ
      hybridizations showed that connexin 26 mRNA was expressed 10-fold higher in
      psoriatic and 4-fold higher in tape-stripped epidermis than in controls. SCCA1
      showed a 40-fold increase in mRNA expression, whereas mitochondrial NAD5 and NAD6
      expression was increased 10- and 20-fold, respectively, in psoriatic skin.
      Northern blots confirmed the increased expression of connexin 26, SCCA1, and NAD6
      genes in psoriatic skin. Immunohistochemistry showed that connexin 26 protein was
      strongly expressed in spinous keratinocytes from psoriatic skin and chronic
      wounds, but was absent in normal epidermis. These studies demonstrate the
      usefulness of this approach for identifying genes that are conditionally
      expressed in growth-activated human skin.

PMID- 9008233
TI  - In vivo transfer of a foreign gene to keratinocytes using the hemagglutinating
      virus of Japan-liposome method.
AB  - The hemagglutinating virus of Japan (HVJ)-liposome method involves the entrapment
      of DNA and nuclear protein within liposomes and the use of HVJ to enhance
      liposome fusion with cell membranes. This method has been used successfully for
      in vivo gene transfer to various types of tissue. In this study, we investigated
      whether this method transfers genes effectively to normal and malignantly
      transformed keratinocytes in vivo. We applied HVJ-liposome complex (HLC)
      containing the beta-galactosidase gene to the tape-stripped skin of hairless rats
      and detected the enzyme activity in the keratinocytes of the treated skin.
      Comparison of this method with the naked DNA injection method, which was shown
      recently to be useful for in vivo gene transfer to keratinocytes, demonstrated
      that the transfer efficiency of the latter was about 5 times higher than that of
      the former. We assessed the efficacy of the HVJ-liposome method for gene transfer
      to transformed keratinocytes by examining the effect of HLC containing the herpes
      simplex virus thymidine kinase gene on the growth of mouse squamous cell
      carcinomas. Local injection of HLC into the tumors followed by administration of
      ganciclovir to mice resulted in tumor growth inhibition. These results indicate
      that the HVJ-liposome method is suitable for in vivo gene transfer to
      keratinocytes; also that this method may prove a good tool for basic research
      into keratinocyte biology and future keratinocyte gene therapy.

PMID- 9008234
TI  - Differential expression of human cornifin alpha and beta in squamous
      differentiating epithelial tissues and several skin lesions.
AB  - Cornifins/small proline-rich proteins (SPRRs) belong to a family of proline-rich
      proteins that function as cornified envelope precursors. We report here an
      immunohistochemical analysis of human cornifin-alpha and -beta expression in
      several stratified squamous epithelia. In normal human skin, cornifin-alpha was
      expressed in the granular layer of the epidermis of palmoplantar skin, in the
      inner lining cells of the follicular infundibulum, and in the inner root sheath
      of the hair follicle. It was also expressed in the upper squamous layers of the
      oral, esophageal, and vaginal epithelia. Cornifin-beta was detected in oral,
      esophageal, and vaginal epithelia, but not in normal skin. Immunoblot analysis
      revealed quantitative differences in cornifin-alpha expression in skin from
      different regions. Studies of specimens from various skin diseases showed that
      (i) cornifin-alpha was upregulated in inflammatory skin diseases, hyperplastic
      lesions, and in well-differentiated squamous cell carcinomas (SCCs), (ii) the
      expression of cornifin-beta was absent in inflammatory skin but was detected in
      highly differentiated keratinocytes in well-differentiated SCCs of the skin and
      some other hyperproliferative skin lesions, and in SCCs of the oral mucosa and
      esophagus. Northern blot analysis revealed that cornifin-alpha mRNA was present
      in all the squamous epithelial tissues studied, whereas cornifin-beta mRNA was
      expressed in oral mucosal epithelia and verrucous carcinoma of the skin but
      neither in normal nor in psoriatic skin. These results indicate that (i) the
      amount of cornifin alpha/SPRR1 expression in normal human skin depends on the
      body region, (ii) cornifin-alpha/SPRR1, but not cornifin-beta, contributes to the
      integrity of the hair follicle, and (iii) the expression of cornifin-beta is
      induced in some hyperplastic skin diseases only when the keratinocytes undergo
      extensive squamous differentiation.

PMID- 9008235
TI  - Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible
      explanation for its hair growth-stimulating effect.
AB  - Data from the literature indicate that nonsteroidal anti-inflammatory drugs
      (NSAIDs), such as indomethacin, naproxen, piroxicam, or ibuprofen, induce hair
      loss in vivo. These NSAIDs are well-known inhibitors of both the cytoprotective
      isoform of prostaglandin endoperoxide synthase-1 (PGHS-1) and of the inducible
      form (PGHS-2). By immunohistochemical staining, we found that PGHS-1 is the main
      isoform present in the dermal papilla from normal human hair follicle (either
      anagen or catagen), whereas PGHS-2 was only faintly and exclusively expressed in
      anagen dermal papilla. Thus, PGHS-1 might be the primary target of the hair
      growth-inhibitory effects of NSAIDs. We thus speculated that activation of PGHS-1
      might be a mechanism by which minoxidil (2,4-diamino-6-piperidinopyrimidine-3
      oxyde) stimulates hair growth in vivo. We demonstrate here that minoxidil is a
      potent activator of purified PGHS-1 (AC50 = 80 microM), as assayed by oxygen
      consumption and PGE2 production. This activation was also evidenced by increased
      PGE2 production by BALB/c 3T3 fibroblasts and by human dermal papilla fibroblasts
      in culture. Our findings suggest that minoxidil and its derivatives may have a
      cytoprotective activity in vivo and that more potent second-generation hair
      growth-promoting drugs might be designed, based on this mechanism.

PMID- 9008236
TI  - The expression of the secreted protein acidic and rich in cysteine (SPARC) is
      associated with the neoplastic progression of human melanoma.
AB  - SPARC (secreted protein acidic and rich in cysteine) is an extracellular protein
      associated with tissues exhibiting high rates of cell proliferation and matrix
      remodeling. The current work shows that the human melanoma cell lines IIB-MEL
      LES, IIB-MEL-IAN, and IIB-MEL-J and different human metastatic melanomas
      expressed high levels of SPARC mRNA and protein. By western blot analysis we
      detected a single secreted 42-kDa band in human diploid fibroblasts-conditioned
      medium and a 45- to 40-kDa doublet in the three melanoma cell lines and all the
      metastatic melanomas tested. Part of the melanoma samples and cell lines showed
      an additional doublet of 36-34 kDa. SPARC mRNA was expressed by the three
      established cell lines, 14 metastatic melanoma samples, and tumors raised in nude
      mice, and no spliced variants were found. The heterogeneous pattern of SPARC
      secreted by human melanoma cells is the result of post-translational
      glycosylation and a specific extracellular leupeptin-inhibitable cleavage. Unlike
      human fibroblasts, melanoma cells did not overexpress SPARC on addition of TGF
      beta. Immunohistochemical analysis showed that SPARC was strongly expressed in
      100% of primary melanomas (7 of 7) and metastatic melanomas (29 of 29),
      moderately expressed in most of the positive dysplastic nevi (13 of 14), and only
      weakly expressed in nevocellular nevi (4 of 25). Normal melanocytes did not
      express SPARC. The data suggest that the expression of SPARC is associated with
      the neoplastic progression of human melanoma.

PMID- 9008237
TI  - Fas signal transduction triggers either proliferation or apoptosis in human
      fibroblasts.
AB  - Although shown to be highly expressed by the epidermis in inflammatory skin
      disease, the ability of the Fas protein to trigger apoptosis in the distinct cell
      subpopulations of cutaneous tissue, particularly with regard to receptor density
      and the degree of crosslinking, has not been fully characterized. We therefore
      determined the effect of Fas cross-linking in primary human dermal fibroblasts at
      both high and low levels of Fas receptor expression. First, we examined the
      effects of the anti-Fas monoclonal antibody, CH-11, on fibroblasts expressing low
      basal levels of Fas. In these cells Fas aggregation stimulated proliferation by
      160 +/- 10% over untreated controls. In contrast, the same concentration of CH-11
      had an inhibitory effect on epidermal keratinocyte growth. Because Fas is
      upregulated in inflamed skin, we next examined the effects of Fas cross-linking
      on fibroblasts expressing augmented levels ofFas. Fibroblasts were either
      transfected with plasmids for overexpression of full length or bioengineered Fas
      receptors or were transduced with a retroviral Fas expression vector. In these
      cells Fas oligomerization triggered the morphologic changes indicative of
      apoptosis regardless of whether or not the Fas-signaling domain was tethered to
      the plasma membrane. These studies indicate that Fas oligomerization in dermal
      fibroblasts may initiate dual signaling programs, either proliferation or
      apoptosis, and that the chosen outcome may depend upon the magnitude of Fas
      aggregation.

PMID- 9008238
TI  - Missense mutations in keratin 17 cause either pachyonychia congenita type 2 or a
      phenotype resembling steatocystoma multiplex.
AB  - Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal
      dysplasias in which the main phenotypic characteristic is hypertrophic nail
      dystrophy. In the Jackson-Lawler form (PC-2), pachyonychia is accompanied by
      multiple pilosebaceous cysts, natal teeth, and hair abnormalities. By direct
      sequencing of genomic PCR products, we report heterozygous K17 missense mutations
      in the same conserved protein motif in a further five PC-2 families (K17 N92S in
      one familial and three sporadic cases; K17 Y98D in one familial case) confirming
      that mutations in this gene are a common cause of PC-2. We also show heterozygous
      missense mutations in K17 (N92H and R94H) in two families diagnosed as
      steatocystoma multiplex. Mild nail defects were observed in some but not all of
      these patients on clinical re-evaluation of these families. All the K17 mutations
      reported here were shown to co-segregate with the disease in the pedigrees
      analyzed and were excluded from 100 unaffected, unrelated chromosomes by
      restriction enzyme analysis of K17 genomic PCR products. We conclude that
      phenotypic variation is observed with K17 mutations, as is the case with other
      keratin disorders.

PMID- 9008240
TI  - Deficiency of glutathione S-transferases T1 and M1 as heritable factors of
      increased cutaneous UV sensitivity.
AB  - Glutathione S-transferases (GSTs) play a primary role in cellular defense against
      electrophilic chemical species and radical oxygen species. Because free radical
      attack is one mechanism of UV irradiation-caused skin damage, we investigated
      whether genetic variation at the GST loci GST T1 and GST M1 influences individual
      UVB sensitivity. In a double-blind clinical trial, 50 healthy volunteers were
      evaluated for minimal erythema dose of UVB irradiation, MED (J/cm2), skin types
      were assigned, and internal standard-controlled polymerase chain reaction (PCR)
      was used to identify their GST T1 and GST M1 genotypes. The five homozygous
      carriers of the GST T1 deletion (GST T1*0/0) presented with the most intensive
      inflammatory reactions after irradiation; they were significantly overrepresented
      among the highly UVB-sensitive subgroups (p = 0.006). Lack of GST M1 (GST M1*0/0,
      n = 27) tended to be more frequent only in UVB-sensitive subjects, and the
      proportion of the active GST M1 allelic variants *A and *B was similar in all UVB
      sensitivity subgroups. Three subjects with deficiencies in GST T1 and GST M1 had
      the most intense inflammatory responses. No effect of gender or genetic
      variations at the MC1R gene locus was established. Thus, heritable GST T1
      deficiency may be a genetic determinant of individual skin sensitivity toward UV
      irradiation.

PMID- 9008239
TI  - Glycine substitution mutations in the type VII collagen gene (COL7A1) in
      dystrophic epidermolysis bullosa: implications for genetic counseling.
AB  - Dystrophic epidermolysis bullosa (DEB) is an inherited mechanobullous disorder
      characterized by fragility of the skin and mucous membranes. The anchoring fibril
      protein, type VII collagen, is encoded by COL7A1, which harbors mutations in this
      group of diseases. In this study, we report novel glycine substitution mutations
      in COL7A1 in two Japanese families with DEB. The mutation detection strategy
      consisted of PCR amplification of genomic DNA, followed by heteroduplex analysis
      and nucleotide sequencing of the PCR products demonstrating altered mobility. The
      first case is a patient with clinically severe recessive DEB. The proband was
      shown to have a homozygous glycine-to-valine substitution (G2671V) in exon 108.
      The clinically unaffected parents were heterozygous carriers of this mutation,
      indicating that this glycine substitution in one allele is "silent" when combined
      with a normal COL7A1 allele. Thus, this patient appeared to be affected with DEB
      inherited in an autosomal recessive pattern. The second case was a DEB patient
      with a heterozygous glycine-to-glutamic acid substitution (G2079E) in exon 75.
      The parents were clinically unaffected and neither had this mutation in their
      peripheral blood leukocyte DNA. Haplotype analyses suggested that this case arose
      as a de novo occurrence of autosomal dominant DEB. These cases illustrate the
      consequences of COL7A1 glycine substitution mutations underlying DEB in terms of
      the mode of inheritance and the phenotype, with profound implications for genetic
      counseling of individuals at risk for recurrence of DEB in subsequent offspring
      or future generations.

PMID- 9008241
TI  - Actinic prurigo and HLA-DR4.

PMID- 9008242
TI  - Plasma renin activity: a risk factor for myocardial infarction in hypertensive
      patients.
AB  - To determine whether pretreatment plasma renin activity (PRA), without
      accompanying 24-h urine sodium, can predict myocardial infarction (MI), the PRA
      levels of 2,902 hypertensive patients [white (38%), male (65%), median age 55
      years], with mean entry blood pressure (BP) of 150/97 mm Hg were examined. During
      an average 3.6 years follow-up (87% > or = 9 months), there were 55 MIs, 21
      strokes, and 16 other cardiovascular disease (CVD) deaths. Classification of PRA
      levels into 3 renin strata [high (H) PRA > or = 4.5 (n = 354), normal (N) 0.75 to
      4.49 (n = 1,622), and low (L) < 0.75 (n = 926) ng/mL/h] yielded subgroups that
      did not differ in LVH (9% v 11%) or smoking prevalence (26% v 25%) but high
      versus low PRA subjects included more aged < 55 years (64% v 53%); white (49% v
      25%); men (79% v 52%); cholesterol > or = 6.3 mmol/L (33% v 25%); all P values <
      .01. MI rates per 1,000/year were H: 9.3, N: 5.5, L: 2.5 (H v L, RR = 3.8, 95%
      CI: 1.7 to 8.4). A similar relationship was seen with total CVD (H: 12.5, N: 9.3,
      L: 5.2; RR = 2.4, 95% CI: 1.3 to 4.5) and all-cause mortality (H: 7.0, N: 6.2, L:
      2.5; RR = 2.8, 95% CI: 1.2 to 6.8) but not CVA (H: 1.6, N: 2.0, L: 1.9). In a Cox
      survival analysis only renin, age, sex, smoking, LVH, and cholesterol were
      significantly (P < .02) related to MI occurrence. There was, for every 2 unit
      increase in PRA, an overall 25% increase in MI incidence. Among hypertensive
      subjects, PRA level (without urine sodium), is independently and directly
      associated with the incidence of MI.

PMID- 9008243
TI  - Reduction in drug requirements for hypertension by means of a cognitive
      behavioral intervention.
AB  - The purpose of the present study was to test the effectiveness of a cognitive
      behavioral intervention as an adjunctive treatment of hypertension. To qualify
      for the study, subjects had to have an unmedicated clinic diastolic blood
      pressure > or = 95 mm Hg. After qualification, minimal drug requirements were
      established using a diuretic and a beta-blocker to control blood pressure at < or
      = 90 mm Hg. Subjects were then randomized into a 6-week cognitive-behavioral
      intervention or a measurements-only control group. After the treatment phase,
      medication levels were reduced in all subjects by means of a systematic stepdown
      procedure. Subjects were followed for 1 year after the stepdown was completed.
      Addition of the cognitive-behavioral intervention was twice as effective as the
      control procedure in reducing drug requirements. At 12-months follow-up, 73% of
      the treatment group were at lower levels of medication than at the time of
      randomization, compared to 35% in the control group. Moreover, 55% of the
      treatment group remained completely free of medication, compared to 30% of the
      control group, at the 12-month follow-up. The reductions in medication were
      associated with maintained controlled levels of clinic, ambulatory, and home
      blood pressure. The addition of a standardized and inexpensive group-administered
      cognitive-behavioral intervention to the drug treatment of hypertension is
      beneficial as an adjunctive treatment in reducing drug requirements for patients
      with hypertension, thereby reducing the costs and potential side effects of
      antihypertensive medications.

PMID- 9008245
TI  - Pressure-heart rate responses to alpha-adrenergic stimulation and hormonal
      regulation in normotensive patients with obstructive sleep apnea.
AB  - Seven normotensive untreated patients with obstructive sleep apnea (OSA) and five
      control subjects without OSA were compared. Patients with cardiac dilation,
      chronic airflow limitation, liver and kidney disease, or diabetes mellitus were
      excluded. Change in pressure-heart rate relation to alpha-adrenergic stimulation
      (P-HRR), extracellular volume (ECV), and plasma volume (Vp) were measured during
      daytime. Plasma atrial natriuretic peptide (ANP), plasma renin and aldosterone
      concentrations were obtained at 1 hour intervals during the night. A mean
      apnea/hypopnea index (AHI) of 52.2 +/- 23.9/h and a mean lowest arterial oxygen
      saturation (SaO2) of 61.2 +/- 19.3% (mean +/- SD) were determined from
      polysomnographic monitoring in the patient group. Release of ANP was
      significantly higher during sleep in OSA patients than in control subjects (P <
      .01), with a maximum concentration between 4 and 6 AM in the former. Daytime ECV
      was significantly higher (P < .05) and Vp significantly lower (P < .05) in OSA
      patients. Night maximum concentration of ANP (max ANP) was negatively related to
      AHI (P < .05). P-HRR was negatively related to AHI (P < .05) and positively
      related to max ANP (P < .05). In conclusion, OSA syndrome alters hormonal system
      control of body fluid compartment regulation. The decreased response in night max
      ANP secretion in the most severe OSA patients could be explained by the smaller
      Vp observed in these patients, decreasing atrial and ventricular pressure
      loading. Furthermore, alteration of P-HRR, correlated to AHI and max ANP,
      strengthens the hypothesis that patients who develop hypertension are those in
      whom the protective mechanism of ANP release failed.

PMID- 9008246
TI  - Effects of protein kinase C activation and inhibition on endothelin-1 release
      from human aortic and pulmonary artery endothelial cells: comparison with effects
      on bovine endothelin-1 and human prostaglandin I2 release.
AB  - Protein kinase C (PKC) has been implicated in the regulation of endothelin-1
      production by bovine and porcine endothelial cells. The role of PKC in the
      synthesis and release of endothelin-1 has not been demonstrated previously in
      human arterial endothelial cells. The effects of activators and an inhibitor of
      PKC on endothelin-1 release from cultured human arterial endothelial cells have
      now been examined. Endothelial monolayers were incubated with the PKC activators
      phorbol 12-myristate 13-acetate (PMA) or 1-oleoyl 2-acetyl glycerol (OAG) for 30
      min to 8 h and the amount of endothelin-1 released into the medium was
      determined. PMA (0.1 micromol/L) and OAG (0.1 mmol/L) stimulated endothelin-1
      release, with maximal increases of 85% and 90%, respectively, apparent at 30 min
      in aortic endothelial cells, and of 81% and 75%, respectively, apparent at 1 h in
      pulmonary artery endothelial cells. Endothelin-1 release had returned to control
      values by 4 h and was approximately one-third to one-half of control values after
      8 h of continuous exposure of both cell types to PMA or OAG. Long-term exposure
      of both types of cells to the PKC inhibitor staurosporine (0.1 micromol/L)
      reduced both basal endothelin-1 release and the enhancement of release by PMA or
      OAG. The PKC agonists also stimulated endothelin-1 release by bovine aortic
      endothelial cells. The maximal effects of PMA and OAG in these cells were
      apparent at 4 h, at which time endothelin-1 release was increased by 154% and
      125%, respectively; after 4 h, endothelin-1 release had decreased, but was still
      132% and 120%, respectively, of the control value at 8 h. The PKC activators
      markedly stimulated prostaglandin I2 (PGI2) release by human pulmonary artery
      endothelial cells. The enhancement of PGI2 release continued for up to 8 h, at
      which time 109-fold and threefold increases in PGI2 release were apparent with
      PMA and OAG, respectively. Therefore, activation of PKC results in a rapid
      increase in endothelin-1 release by human arterial endothelial cells. The
      subsequent decrease in endothelin-1 release in the presence of PMA or OAG is
      presumably attributable to activator-induced downregulation of PKC, which was
      apparent earlier in human than in nonhuman endothelial cells. The downregulation
      of endothelin-1 release also occurred much earlier than that of PGI2 release in
      human pulmonary artery endothelial cells.

PMID- 9008244
TI  - 24-h ambulatory blood pressure monitoring in healthy young adult Anglo, Hispanic,
      and African-American subjects.
AB  - The purpose of this study was to compare office and 24-h ambulatory blood
      pressure (ABP) values for adolescent and young adult males and females of Anglo,
      Hispanic, and African-American descent. One hundred and eighteen healthy subjects
      (62 females, 56 males) participated, with an ethnic distribution of 50 Anglo, 32
      Hispanic, and 36 African-American subjects. All subjects came to the clinic for
      height, weight, sitting blood pressure (BP), and to begin 24-h ABP monitoring
      using the SpaceLabs model 90207 automatic noninvasive monitor. The monitor
      recorded readings every 0.5 h from 06:00 to 22:00 and every hour at night from
      22:00 to 06:00. Office systolic and diastolic BP values were higher for all males
      compared to all females. Mean 24-h, nighttime, and daytime systolic ABP values
      were also significantly higher for males compared to females. The 24-h mean and
      daytime systolic ABP values were significantly different by ethnic groups. The
      African-American subjects always had the highest readings. Mean 24-h diastolic
      ABP was also significantly different by ethnic groups, with the African-American
      subjects being higher than the Anglos or the Hispanics. Diastolic ABP (24-h mean,
      daytime, and nighttime) values (for all subjects combined) increased gradually
      and varied significantly with age. This study provides preliminary normative data
      about ABP in an understudied population (ie, teenagers and young adults of
      different ethnic backgrounds). It also shows that higher blood pressures are
      present among males and among subjects of African-American descent in the teenage
      and young adult population.

PMID- 9008247
TI  - Vascular growth responses in SHR and WKY during development of renal (1K1C)
      hypertension.
AB  - Intrinsic differences between vascular smooth muscle cells (VSMC) in normotension
      and genetic hypertension may account for the exaggerated growth response often
      observed in the hypertensive vasculature. To test this hypothesis, in this study
      we compared the vascular growth response of the spontaneously hypertensive rat
      (SHR) and Wistar-Kyoto rat (WKY) following induction of one kidney, one clip
      (1KlC) renal hypertension. SHR and WKY rats were uninephrectomized and renal
      hypertension (RH) induced using silver clips of 0.22 and 0.24 mm width. Four
      weeks later, vessel and VSMC growth were assessed in small mesenteric arteries.
      The systolic blood pressure (SBP) in the RH animals was significantly higher than
      in uninephrectomised controls, in RH-SHR with a 0.24 mm clip SBP averaged 215 +/-
      4 mm Hg and in RH-WKY with a 0.22 or 0.24 mm clip the SBPs averaged 214 +/- 5 mm
      Hg and 190 +/- 2 mm Hg, respectively. For the same SBP, there were no differences
      in medial cross-sectional areas of the small mesenteric arteries between RH-SHR
      and RH0.22-WKY, which averaged 1.73 +/- 0.19 x 10(4) microm2 and 1.66 +/- 0.15 x
      10(4) microm2, respectively. Likewise, the number of VSMCs (within a precise
      anatomical site of the mesenteric vasculature) were not different between the RH
      SHR and the RH0.22-WKY with VSMC number 7.6 +/- 0.8 x 10(4) cells and 6.9 +/- 0.4
      x 10(4) cells, respectively. In the RH0.22-WKY vascular growth responses were
      generally unchanged compared with the RH0.24-WKY except for a further increase in
      the incidence of polyploid cells. In conclusion, the results of this study
      demonstrate that smooth muscle cells of the SHR are not hyperresponsive to all
      growth-promoting stimuli. Taken together with previous observations, it appears
      that sustained activity of the renin-angiotensin system may be required for
      exaggerated vascular growth responses in SHR.

PMID- 9008248
TI  - Endothelial injury in transgenic (mRen-2)27 hypertensive rats.
AB  - Transgenic [(mRen-2)27] rats develop severe hypertension as the result of
      transfection with the mouse Ren-2 gene. This study tested the hypothesis that
      hypertensive [(mRen-2)27] rats have increased endothelial dysfunction by
      examining the extent of vascular endothelial cell injury and turnover within the
      thoracic aorta of age-matched female transgene positive [Tg(+)] and transgene
      negative [Tg(-)] littermates. Transgenic hypertensive rats had arterial pressures
      significantly higher than Tg(-) animals, but no differences in heart rate or body
      weight. The extent of endothelial cell injury was estimated in Hautchen
      preparations of thoracic aorta endothelium by counting cells immunostained for
      the presence of cytoplasmic immunoglobulin G (IgG) at sites with or without
      intercostal artery branches. Both Tg(+) and Tg(-) littermates had a greater
      percentage of injured endothelial cells at branch sites than at nonbranch aorta
      (P < .01). However, the number of vascular endothelial cells staining positively
      for IgG was significantly higher in hypertensive rats both at sites away from (P
      < .05) and in the immediate vicinity of (P < .1) the orifices of intercostal
      arteries. En face preparations of the thoracic aorta were also examined for cells
      incorporating 5-bromo-2 '-deoxyuridine (BrdU) to estimate the percentage of
      endothelial cells undergoing replication. There was no difference in endothelial
      cell replication at either branch or nonbranch sites between hypertensive and
      normotensive rats. However, the percentage of endothelial cells undergoing
      replication at branch sites in both Tg(+) and Tg(-) rats was significantly
      greater than at nonbranch sites (P < .01). These data provide the first
      demonstration for the effects of high blood pressure on the vascular endothelium
      of a monogenetic model of hypertension produced by increased activity of the
      renin-angiotensin system. The divergent effects of this form of hypertension on
      vascular endothelial injury and endothelial turnover suggest that the decrease in
      the reparative capacity of the vascular endothelium induced by the combination of
      hypertension and associated angiotensinemia may contribute to the endothelial
      dysfunction accompanying vascular remodeling.

PMID- 9008249
TI  - A randomized study comparing a patient-directed hypertension management strategy
      with usual office-based care.
AB  - This study aimed to compare the efficacy of a patient-directed management
      strategy with office-based management in maintaining blood pressure control in
      patients with chronic stable hypertension using a randomized trial of two months
      duration. The subjects had chronic stable essential hypertension without
      secondary causes or unstable cardiovascular disease and were selected through the
      offices of 11 family physicians and a tertiary care hypertension research unit.
      Patients were randomly assigned (2:1 ratio) to either a patient-directed
      management strategy using home blood pressure monitoring to adjust drug therapy
      if readings consistently exceeded defined limits, or office-based management
      through physician visits. The primary endpoint was the change from baseline in
      mean arterial pressure as determined by automatic ambulatory blood pressure
      monitoring. Secondary endpoints were changes in compliance, quality of life, and
      health care resource use. Ninety-one potential subjects were screened and 31 were
      randomized. Subjects in the patient-directed management group employed the drug
      adjustment protocols appropriately without complications. A significant
      difference in change in mean blood pressure was observed, favoring the patient
      directed management (-0.95 mm Hg and +1.90 mm Hg, respectively, for patient
      directed management and office-based management, P = .039). Compliance rates and
      quality of life scores were not significantly different between groups. Physician
      visits were more frequent in the patient-directed management group (1.05 v 0.20
      visits/8 weeks, respectively, for patient-directed management and office-based
      management groups, P = .045). A patient-directed hypertensive management strategy
      may be feasible for patients with chronic stable hypertension. Such a strategy
      may improve blood pressure control compared with usual office-based care.
      However, physician visits may be increased using this strategy, at least in the
      short term.

PMID- 9008251
TI  - Sympathetic nerve hyperactivity precedes hyperinsulinemia and blood pressure
      elevation in a young, nonobese Japanese population.
AB  - To evaluate the relationships between sympathetic nerve activity, insulin
      sensitivity, and blood pressure (BP) elevation, we examined BP, fasting blood
      glucose, plasma insulin, and norepinephrine (NE) levels in age- and body mass
      index (BMI)-matched 662 normotensive (NT) and 188 borderline hypertensive (BHT)
      subjects every year for 10 years. All measurements were taken in the supine
      position after an overnight fast. BP elevation (BP-E) during 10 years was defined
      as 10% or more elevation of mean BP when compared with BP at entry. BP-E was
      noted in 186 (28%) of NT and in 52 (28%) of BHT. Fasting insulin level at entry
      in BHT with BP-E was significantly greater than that in subjects without BP-E (P
      < .01), although fasting insulin level in NT with BP-E at entry was similar to
      that in NT without BP-E. Supine plasma NE level at entry period and year 10 in NT
      with BP-E was significantly greater than that in subjects without BP-E (P < .05,
      P < .01, respectively). Supine NE in BHT regardless of BP-E was significantly
      greater than that in NT at both entry and year 10. These results demonstrate that
      sympathetic nerve hyperactivity appears to precede hyperinsulinemia and resultant
      BP elevation in a young, nonobese Japanese population.

PMID- 9008250
TI  - Blood pressure and metabolic responses to moderate sodium restriction in
      isradipine-treated hypertensive patients.
AB  - This multicenter, randomized, controlled clinical trial assessed the influence of
      sodium chloride intake on the antihypertensive effect of the calcium channel
      blocker isradipine. Participants with uncomplicated hypertension controlled by
      isradipine entered a 4-week sodium-restricted (60 to 80 mmol/24 h) period.
      Participants with urinary sodium levels < 120 mmol/24 h (n = 99) were randomized
      to placebo or sodium chloride (100 mmol/24 h) for 4 weeks, and then crossed over
      to the alternative treatment for an additional 4 weeks. Mean baseline systolic
      blood pressure was 151.9 +/- 16.7 mm Hg (mean +/- SD). During open-label
      isradipine treatment, systolic blood pressures for ad libitum sodium chloride and
      restriction were 134.1 +/- 11.1 and 132.1 +/- 12.2 mm Hg respectively; for double
      blind sodium chloride restriction and supplementation: 133.6 +/- 12.6 and 138.5
      +/- 12.8 mm Hg (P < .01). Urinary sodium excretion values for open-label
      isradipine ad libitum versus restricted were 140.6 +/- 61.9 versus 76.9 +/- 32.4
      mmol/24 h; for double-blind restricted versus supplemented, sodium excretion was
      120.5 +/- 68.9 v 175.9 +/- 68.7 mmol/24 h (P < or = .0001). Changes in urinary
      sodium excretion were not predictive of variations in blood pressure. Urinary
      sodium excretion during sodium restriction correlated directly with HDL
      cholesterol (P < .02) and inversely with total cholesterol:HDL-cholesterol (P =
      .02), despite decreased total and saturated fat intake (P < .01). Sodium
      restriction was associated with significant reductions (P < .01) in virtually all
      macronutrients and electrolytes, and thus had an adverse impact on overall
      nutrition. The antihypertensive action of isradipine was not enhanced by dietary
      sodium chloride restriction, and the lipoprotein profile was least favorable with
      sodium chloride restriction.

PMID- 9008252
TI  - Angiotensin converting enzyme inhibition corrects Na+/H+ exchanger overactivity
      in essential hypertension.
AB  - In this study, we investigated whether antihypertensive treatment with the
      angiotensin converting enzyme inhibitor quinapril modifies Na+/H+ exchanger
      activity or NHE-1 (isoform of the exchanger) mRNA expression in lymphocytes from
      patients with essential hypertension. Thirty-three hypertensive patients and 27
      normotensive subjects were studied. Maximal sodium-proton exchange activity was
      determined by acidifying cell pH and measuring the initial rate of the net sodium
      dependent proton efflux driven by an outward proton gradient. The transcript
      level of NHE-1 was measured by reverse transcription-polymerase chain reaction in
      comparison with a constitutively expressed reference gene (beta-actin). With the
      100% confidence (upper) limit of the normotensive population as a cutoff point, a
      subgroup of 11 hypertensive patients had an abnormally high lymphocyte Na+/H+
      exchange activity (group A). The activity of the exchanger was within the normal
      range in the remaining patients (group B). After 6 months of quinapril treatment
      the activity of the exchanger decreased to normal values (P < .001) in patients
      from group A, but remained unchanged in patients from group B. The NHE-1 mRNA
      expression was not modified with treatment neither in patients from the group A,
      nor in patients from the group B. These results suggest that chronic angiotensin
      enzyme inhibition with quinapril abolishes Na+/H+ exchange overactivity present
      in lymphocytes from a subgroup of hypertensive patients. This effect appears to
      be independent of changes in the expression of the mRNA encoding for the NHE-1
      isoform of the exchanger.

PMID- 9008253
TI  - Effect of short-term treatment of SHR with the novel calcium channel antagonist
      mibefradil on function of small arteries.
AB  - Treatment of spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats
      (WKY) for at least 12 weeks with calcium channel antagonists is associated with
      regression of structural hypertensive changes in the heart and in conduit and
      small arteries. To establish whether structural or functional changes of small
      arteries could be corrected with shorter periods of specific antihypertensive
      treatment, SHR and WKY were treated for 4 weeks with the novel calcium channel
      blocker mibefradil. Blood pressure rise was significantly reduced by mibefradil
      treatment in SHR to 165 +/- 1 mm Hg compared to a systolic blood pressure of 183
      +/- 2 mm Hg in untreated SHR (P <.01). Aortic hypertrophy in SHR was slightly
      reduced by treatment, but small artery hypertrophy in 4 vascular beds
      (mesenteric, renal, coronary, and femoral) was unaffected by administration of
      mibefradil for 4 weeks. Mibefradil treatment resulted in normalization of
      endothelium-dependent relaxation in mesenteric small arteries, with disappearance
      of acetylcholine-induced contractions, although hypertrophy and remodeling of
      these small arteries were not significantly affected by treatment. In WKY rats,
      treatment had no effect on either structure or function of small arteries. These
      results demonstrate that treatment with the calcium antagonist mibefradil may
      induce an improvement in altered endothelial function even before regression of
      cardiovascular hypertrophy and remodeling takes place under treatment, indicating
      that normalization of abnormal small artery endothelial function in SHR under
      antihypertensive therapy may be independent of correction of altered small artery
      structure.

PMID- 9008254
TI  - Trp64Arg mutation of beta3-adrenergic receptor in essential hypertension: insulin
      resistance and the adrenergic system.
AB  - A putative pathogenic mutation in the beta3-adrenergic receptor gene (Trp64Arg)
      has been reported to be associated with higher diastolic blood pressure as well
      as clinical features of the insulin resistance syndrome and an earlier onset of
      non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians and Finns.
      Because essential hypertension is reported to be associated with insulin
      resistance, we studied the mutation in Japanese patients with essential
      hypertension to clarify associations of this mutation with hypertension, insulin
      resistance, and basal adrenergic state in hypertensive subjects. The allele
      frequency of the mutation (Arg) in patients with essential hypertension was
      similar to that in control subjects (35 of 202 alleles [17.3%] v 27 of 146
      [18.5%], respectively, P > .7). Insulin sensitivity measured by hyperinsulinemic
      euglycemic glucose clamp and plasma norepinephrine and epinephrine levels were
      also similar in hypertensive subjects with and without the mutation. These data
      suggest that Trp64Arg mutation in the beta3-adrenergic receptor gene does not
      play a major role in susceptibility to essential hypertension or in insulin
      resistance and basal adrenergic state in hypertension.

PMID- 9008255
TI  - Blood pressure responses to exercise as predictors of blood pressure level after
      5 years.
AB  - There is considerable disagreement in the literature on the clinical usefulness
      of exercise testing as a tool for prediction of future hypertension. Much of the
      discrepancy between various reports is attributable to the difficulties of blood
      pressure (BP) measurement during exercise. Therefore, we investigated whether
      accurate intraarterial BP measurement will increase the predictive power of
      exercise testing. The BP responses to dynamic and isometric exercise were
      evaluated in 97 healthy, unmedicated men, of whom 34 were normotensive (NT), 29
      borderline (BHT), and 34 mildly hypertensive (HT) using three criteria: 1)
      achieved BP during the test, 2) the change of the BP from baseline to exercise,
      and 3) the group was divided into high responders (HIGH, n = 19, systolic BP > or
      = 220 and diastolic BP > or = 105 mm Hg) and normal responders (n = 60). Five
      years later the BP was reassessed by casual measurements and noninvasive
      ambulatory 24-h monitoring (NAMB) in 79 (81%; 27 NT, 24 BHT, and 28 HT) subjects.
      The achieved isometric BP correlated well with the follow-up BP (casual systolic
      BP r = 0.43, diastolic BP r = 0.45, and NAMB systolic BP r = 0.44, diastolic BP r
      = 0.58, P < .001). However, achieved dynamic BP showed a poorer relationship to
      future BP (r range, 0.09 to 31, P = NS to P < .01). Because the intraarterial
      preexercise sitting BP also correlated well with follow-up BP (r range, 0.33 to
      0.48, P < .01 to P < .001), and the r values were close to those of achieved
      isometric BP we used multiple regressions (including all resting and exercise BP
      values as independent variables) to evaluate the contributions of the baseline
      and exercise values for prediction of the follow-up BP. The baseline value
      explained 12% to 23% (from casual diastolic BP to NAMB diastolic BP, systolic BP
      values) of future BP variance, whereas achieved isometric BP ranged an additional
      1% to 11% (from casual systolic BP to NAMB diastolic BP) of variance. In general,
      BP change from baseline with stressors did not correlate with follow-up
      measurements. In the high responder group the achieved dynamic BP did not
      correlate significantly with the follow-up BP, whereas the achieved isometric
      diastolic BP did correlate (casual diastolic BP r = 0.56, P < .05, NAMB systolic
      BP and diastolic BP r = 0.52, P < .05). Both groups had similar future BP levels.
      In conclusion, even with very accurate BP readings the reactivity to dynamic
      exercise is a weak predictor of future BP, and does not improve the prediction
      compared to resting BP values. Intraarterial BP response to isometric exercise
      marginally improves the prediction of future BP levels.

PMID- 9008256
TI  - Use of the factorial design and quadratic response surface models to evaluate the
      fosinopril and hydrochlorothiazide combination therapy in hypertension.
AB  - The combination of angiotensin converting enzyme (ACE) inhibitor and thiazide
      diuretic has advantages over monotherapy for the treatment of hypertension.
      Previous study designs have often been inadequate to demonstrate the details of
      interactions between these antihypertensive agents. This study used a modified 4
      x 4 factorial randomized, double-blind, placebo-controlled, parallel group design
      to study the efficacy of 17 different doses of fosinopril (Fos), a phosphinic
      acid derived ACE inhibitor, and hydrochlorothiazide (HCTZ) in 550 patients with
      mild to moderate hypertension. Data from these variables were fit to quadratic
      response surface models (QRSM) using polynomial functions in the doses of the two
      components. Using QRSM, seated systolic (SeSBP) and diastolic blood pressure
      (SeDBP) responses at 8 weeks were predicted for actual doses and interpolated for
      intermediate doses not studied. Fos and HCTZ alone and in combination produced a
      dose-related reduction in SeSBP and SeDBP. Using 10 mg Fos + 12.5 mg HCTZ reduced
      the adjusted mean SeDBP 6.3 mm Hg and 20 mg Fos + 12.5 mg HCTZ lowered the same
      measure 9.1 mm Hg. Coadministration of Fos and HCTZ produced an additive
      antihypertensive effect. This study of combination agents for hypertension using
      a factorial design with QRSM accurately predicts dose responses and is a valuable
      clinical trial methodology.

PMID- 9008257
TI  - Isosorbide nitrates, nitroglycerin, and sodium nitroprusside induce vasodilation
      concomitantly with inhibition of carbonic anhydrase I in erythrocytes.
AB  - This study describes the relationship between nitroglycerin, isosorbide
      dinitrate, sodium nitroprusside, and carbonic anhydrase I, as well as the
      involvement of this carbonic anhydrase I in vasodilation. Two groups of coronary
      patients and a group of rabbits underwent treatment with the above-mentioned
      vasodilating drugs. The activity of red blood cell carbonic anhydrase was
      monitored and determined by the stopped-flow method. The results show that these
      drugs inhibit the activity of the isozyme in parallel to their vasodilating
      effect. The results of this study lead to the hypothesis that through the pH
      modifications induced by these vasodilators by the inhibition of carbonic
      anhydrase I, the isozyme may be involved in the regulation of vascular tonus.

PMID- 9008258
TI  - Nitric oxide, the kidney, and hypertension.
AB  - The acute administration of nitric oxide (NO) synthesis inhibitors reduces the
      renal capacity to excrete sodium under normal or volume expanded conditions and
      increases renovascular resistances in the absence of changes in systemic blood
      pressure (BP). This indicates a sensitivity of renal vasculature higher than that
      of systemic vessels to NO synthesis inhibition. Medullary circulation is the
      renovascular territory most dependent on NO availability. Thus, alterations in
      medullary blood flow seems to account for the blunted pressure-natriuresis and
      sodium retention during acute NO synthesis inhibition. By contrast, during
      chronic administration of L-arginine analogs, systemic BP rises and overrides
      initial sodium retention by a resetting of the pressure-natriuresis relationship.
      This BP increase appears to be dependent on an overexpression of the actions of
      vasoconstrictor systems due to an imbalance created by the diminished NO
      production. Prolonged NO synthesis inhibition not only elevates BP, but also
      produces renal vascular and parenchymal damage. Antihypertensive therapy impedes
      BP elevation and ameliorates kidney deterioration. Finally, there is evidence of
      the possibility that a certain alteration in the L-arginine-NO pathway exists in
      genetic models and in human essential hypertension. In conclusion, according to
      the data contained in the literature, NO plays a significant role in the
      regulation of systemic and renal hemodynamics and excretory function, and could
      participate in the development of hypertension.

PMID- 9008260
TI  - Use of the acronym SMART in a title is not very smart.

PMID- 9008259
TI  - Comments on the study by Pahor et al. STEPHY Investigators.

PMID- 9008261
TI  - ALLHAT and calcium channel blockers. ALLHAT Research Group.

PMID- 9008262
TI  - Accuracy of the Dinamap 8100.

PMID- 9008263
TI  - Use of antihypertensive drugs in an intensive care unit.

PMID- 9008265
TI  - A computer program using disposition decomposition analysis in pharmacodynamics.
AB  - A personal computer based program (DDAPD1) was developed for calculating or
      determining the apparent distribution function of a drug to a possibly
      heterogeneous biophase, the mean transit time of a drug at the biophase, the
      ratio of distribution clearance to biophase volume of distribution, the drug
      concentration-time function at the biophase (Cb(t)), and a function which
      reflects the relationship between the pharmacodynamic response and Cb(t) of the
      drug. This program uses an approach based on disposition decomposition analysis
      and the hysteresis minimization principle. The application of the program is
      demonstrated using published data for heptabarbital.

PMID- 9008264
TI  - Comparative absorption of bismuth in Sprague-Dawley rats following oral
      administration of preparations containing bismuth sucrose octasulfate, bismuth
      subsalicylate, and bismuth subcitrate.
AB  - The absorption of bismuth from De-Nol (bismuth subcitrate, DN), Pepto-Bismol
      (bismuth subsalicylate, PB) and bismuth sucrose octasulfate (BISOS) was examined
      in male Sprague-Dawley rats after a single oral dose of each compound (60mg
      bismuth). Bismuth was analysed in blood, urine, kidney, brain, liver, and lung
      using graphite furnace atomic absorption spectrophotometry. Bismuth Cmax averaged
      18.4 +/- 11.6 ng mL(-1) for BISOS, 292 +/- 130 ng mL(-1) for DN, and 21.5 +/-
      9.63 ng mL(-1 ) for PB. Cmax was significantly lower for BISOS compared to DN
      (p<0.05) but not significantly different for BISOS compared to PB (p > 0.05).
      Bismuth AUC was 1356 +/- 474 ng h(-1) mL (-1) for BISOS, 2129 +/- 452 ng h(-l)
      mL(-1) for DN, and 1824 +/- 919 ng h(-1) for PB, which indicated a lower extent
      of absorption from BISOS compared to DN. Kidney, liver, and lung levels of
      bismuth were also significantly lower for BISOS compared to DN (p < 0.05).
      Bismuth urinary excretion was significantly lower for BISOS (0.04 +/- 0.02%)
      compared to DN (0.27 +/- 0.15%) but not significantly different compared to PB
      (0.07 +/- 0.03%). These data suggest that the absorption of bismuth following
      oral administration of bismuth sucrose octasulfate is significantly lower than
      that from De-Nol and similar to that from Pepto-Bismo.

PMID- 9008266
TI  - The distribution of 10-hydroxy carbazepine in blood compartments.
AB  - The distribution of 10-hydroxy carbazepine (MHD), the main metabolite of
      oxcarbazepine (OXC), was investigated in plasma and red cells. After the oral
      administration of 600mg of OXC to nine healthy volunteers, blood samples were
      withdrawn for the next 56h and packed red cells were separated from plasma by
      centrifugation. Also, in vitro studies of plasma binding of MHD were carried out
      by a dialysis technique. Results showed that the in vitro protein binding was
      low. The mean bound concentration ranged from 37 to 40%; however, an affinity of
      MHD to red corpuscles was found. These observations indicate that MHD red blood
      cell concentrations together with plasma measurements could be useful in cases of
      inefficacy or toxicity in order to make the appropriate drug adjustments.

PMID- 9008267
TI  - Intestinal absorption of captopril and two thioester analogs in rats and dogs.
AB  - The objectives of this study were (i) to determine whether the reduced absorption
      of captopril from the colon of humans also occurs in rats and (ii), after
      confirmation of the relevance of a new rat model, to evaluate the intestinal
      absorption of captopril and several of its analogs. A model was developed and
      validated in which specific sites within the GI tract of rats were surgically
      implanted with a cannula such that animals could be dosed while conscious and
      unrestrained. The absorption of captopril after administration into the lower GI
      tract of rats was significantly reduced relative to the upper GI tract, which was
      consistent with results reported previously in humans. In rats, the absorption of
      the S-benzoyl thioester prodrug of captopril (SQ-25868) from the lower GI tract
      was substantially greater than that of captopril. However, the absorption of the
      S-benzoyl thioester prodrug of 4-phenyl thio-captopril (SQ-26991) from the lower
      GI tract was only marginally better than that of captopril. In additional studies
      in dogs, a 12h controlled-release formulation of SQ-25868 provided sustained
      blood levels of captopril while maintaining acceptable bioavailability (> 80%).
      Two approaches were tried, without success, to stabilize captopril in vivo: (i)
      complexation with zinc (SQ-26284) and (ii) use of ascorbic-acid-buffered (pH 3.5)
      vehicle. The zinc complex might have failed because it has very low solubility,
      whereas the pH-3.5-buffered vehicle was quickly neutralized within the colonic
      lumen in rats, and did not stabilize captopril against oxidation. Rapid
      neutralization might explain why the colonic bioavailability of captopril was not
      substantially increased when this pH-3.5-buffered vehicle was tried in humans.

PMID- 9008268
TI  - The effect of intravenous infusion time on the pharmacokinetics and
      pharmacodynamics of the same total dose of azosemide in rabbits.
AB  - The pharmacokinetics and pharmacodynamics of azosemide were evaluated after
      intravenous (IV) administration of the same total dose of azosemide, 1 mgkg(-l)
      in different infusion times, 1 min (treatment I) and 4h (treatment II) to rabbits
      (n= 5, each). The loss of water and electrolytes in urine induced by azosemide
      was immediately replaced with infusion of equal volume of lactated Ringer's
      solution. Some pharmacokinetic parameters of azosemide were different between
      treatments I and II. For example, the mean value of terminal half-life (70.5
      versus 107 min), total body clearance (5.88 versus 8.32 mL min(-1)kg(-1), renal
      clearance (3.45 versus 6.51mL min(-1)kg(-1), and mean residence time (18.5 versus
      31.7min) increased significantly in treatment II. The 8h urine output (236 versus
      733mL) and 8h urinary excretion of sodium (29.2 versus 76.4mmol) and chloride
      (27.5 versus 78.9 mmol) increased significantly in treatment II although the
      total amount of 8h urinary excretion of unchanged azosemide increased by only 15%
      in treatment II. This could be due to the fact that the urinary excretion rates
      of azosemide in treatment II remained for a longer period of time close to the
      maximally efficient urinary excretion rates of azosemide for both urine output
      and urinary excretion rates of sodium than in treatment I. Plasma concentrations
      of azosemide and hourly urine output and hourly urinary excretion of azosemide,
      sodium, potassium, and chloride during the apparent steady state (between 2 and 4
      h) in treatment II were fairly constant.

PMID- 9008269
TI  - Effect of portal vein ligation and silymarin treatment on aspirin metabolism and
      disposition in rats.
AB  - The influence of portal hypertension on the metabolism and pharmacokinetics of
      aspirin was evaluated after the administration of a single oral dose of
      acetylsalicylic acid (20 mgkg(-1)) in portal-vein-ligated (PVL) rats. Experiments
      were also performed in control (sham-operated rats) and in rats that received an
      oral daily dose (150 mgkg(-1)) of silymarin from the tenth day after surgery for
      7 d. Plasma concentration profiles of all groups exhibited monoexponential decay
      but with important changes in pharmacokinetic parameters. The aspirin elimination
      constant (k) for PVL rats was lower than for control rats, whereas the plasma
      half-life and area under the curve were greater than those in the control group.
      However, Cmax was comparable with that of the control rats. Urinary excretion of
      the metabolites (salicylic acid and glucuronides) was significantly altered in
      PVL rats: the urinary glucuronides were reduced and urinary salicylic acid was
      increased. The activities of plasma and liver esterases were increased
      significantly in PVL rats, while the activity of p-nitroanisole-O-demethylase was
      not affected. Depletion of cytochrome P 450 was also noted in the same group of
      rats. Silymarin markedly reversed the alterations found in the PVL group.

PMID- 9008270
TI  - A multiple-dose pharmacokinetic interaction study between didanosine (Videx) and
      ciprofloxacin (Cipro) in male subjects seropositive for HIV but asymptomatic.
AB  - The pharmacokinetics of didanosine and ciprofloxacin were evaluated following the
      administration of multiple oral doses of each drug as a single agent or in
      combination. Didanosine was dosed as the Videx chewable/dispersible tablet, which
      contains the antacids dihydroxyaluminum sodium carbonate and magnesium hydroxide.
      Sixteen HIV-seropositive male subjects were randomly assigned to two groups of
      eight each. Group A received didanosine (200 mg q 12h) for 3d, followed by
      didanosine (200 mg q 12h) and ciprofloxacin (750 mg q 12h) for 3d, and finished
      with another course of didanosine (200 mg q 12h for 3 d). Group B began with
      ciprofloxacin, followed by the combination, and finished with ciprofloxacin using
      the same doses and schedule as utilized in group A. During the combination phase
      of the study, ciprofloxacin was administered 2 h prior to didanosine. Serial
      blood and urine samples were collected on study days 4, 8, and 12 for the
      quantitative determination of didanosine and ciprofloxacin using validated HPLC
      methods. The plasma and urine data were subjected to noncompartmental
      pharmacokinetic analysis. A statistically significant decrease in the average AUC
      and UR values of ciprofloxacin was noted when it was given with didanosine,
      relative to administration as a single agent. However, the magnitude of the
      decrease in these parameters, approximately 26 and 29%, respectively, was not
      considered clinically significant. The apparent decrease in the bioavailability
      of ciprofloxacin was probably due to the formation of a chelation complex between
      it and the aluminum- and magnesium-containing antacids found in the didanosine
      tablet. Other than an approximately 16% decrease in AUC, ciprofloxacin did not
      alter the pharmacokinetics of didanosine. The data from the present study
      demonstrate that didanosine or ciprofloxacin can be added to a treatment regimen
      consisting of the other single agent and that cessation of treatment with one
      agent does not have an impact on the pharmacokinetics of the other drug. The dose
      of ciprofloxacin must be taken at least 2h prior to didanosine to avoid a
      clinically significant interaction with the antacids present in the didanosine
      formulation.

PMID- 9008272
TI  - Major technological advances affecting clinical and diagnostic immunology.

PMID- 9008271
TI  - The effect of experimental renal failure on tolfenamic acid disposition in the
      dog.
AB  - The pharmacokinetic disposition of tolfenamic acid, an NSAID, after a single
      administration of tolfenamic acid (4 mg kg(-1)) by the intravenous (IV) route was
      compared in eight dogs before and after a surgically induced renal failure. Renal
      impairment was confirmed by a significant increase (p <0.001) of water intake,
      urine volume, and urea and creatinine plasma concentration. PAH and inulin
      clearances decreased after surgery from 15.2 +/- 4.2 to 9.5 +/- 0.8 mL kg(-1)
      min(-1) (p < 0.05) and from 4.37 +/- 1.15 to 2.43 +/- 0.88 mL kg(-1) min(-1)
      (p=0.067),respectively. After surgery, clearance of TA was significantly (p
      <0.001) increased, from 2.22 +/- 1.68 to 3.59 +/- 1.81 mL kg (-1) min(-1). There
      was no modification of the steady-state volume of distribution (p > 0.05) and the
      mean residence time was significantly decreased from 606 +/- 199 to 373 +/- 302
      min (p < 0.05). No variation of binding to plasma proteins (> or = 99%) was
      observed. These results suggest that renal insufficiency could increase hepatic
      metabolism and/or alter the enterohepatic cycle of TA.

PMID- 9008273
TI  - A semiquantitative assay for CD8+ T-cell-mediated suppression of human
      immunodeficiency virus type 1 infection.
AB  - A reproducible, semiquantitative assay was developed to measure the level of the
      anti-human immunodeficiency virus type 1 (anti-HIV-1) suppressive activity of
      CD8+ T cells. The assay had a wide dynamic range and could be applied to a
      relatively small number of fresh and cryopreserved peripheral blood mononuclear
      cells and purified CD8+ T cells. The suppressive activity was not due to
      cytolytic activity and was not major histocompatibility complex class I
      restricted. Suppression of HIV-1 infection by CD8+ T cells was consistently
      demonstrable with both endogenously infected autologous CD4+ T cells and
      exogenously infected allogeneic CD4+ T cells. This assay can be used to monitor
      the level of antiviral activity of CD8+ T cells in a retrospective and
      prospective manner in studies of the natural history of HIV-1 infection and of
      subjects receiving anti-HIV-1 therapy and vaccines.

PMID- 9008274
TI  - Molecular karyotype analysis of Cryptosporidium parvum: evidence for eight
      chromosomes and a low-molecular-size molecule.
AB  - We report improved separation of chromosome-sized DNA molecules of the coccidian
      parasite Cryptosporidium parvum with contour-clamped homogeneous electric fields
      (CHEF). We used scanning densitometry to determine that the most likely number of
      chromosomes is eight. Molecular probes consisting of cloned genes were used to
      distinguish each of five bands visible on CHEF gels. We have also identified a
      low-molecular-size DNA molecule possibly related to the 35-kb circular DNAs found
      in other Apicomplexa.

PMID- 9008275
TI  - Mycobacterium tuberculosis induces apoptosis in gamma/delta T lymphocytes from
      patients with advanced clinical forms of active tuberculosis.
AB  - Antigens from inactivated Mycobacterium tuberculosis H37Ra induce activation in a
      subpopulation of gamma/delta (gamma/delta) T lymphocytes in a manner that
      resembles that of superantigens from alpha/beta T cells. After culture in vitro
      with H37Ra proteins, gamma/delta T lymphocytes from patients with advanced
      clinical forms of active tuberculosis (ACF-TBC) display cytotoxic activity
      against homotypic target cells exposed to H37Ra. Cytotoxicity by gamma/delta T
      lymphocytes from ACF-TBC patients occurs in a range similar to that observed in
      healthy subjects. Following activation, H37Ra-stimulated gamma/delta T
      lymphocytes from healthy subjects did proliferate in the presence of exogenous
      recombinant human interleukin 2. However, under the same conditions, gamma/delta
      T lymphocytes from ACF-TBC patients not only did not proliferate but died by
      apoptosis. These results suggest that in gamma/delta T lymphocytes from patients
      with ACF-TBC, antigens from M. tuberculosis may induce cell activation that leads
      to apoptotic cell death.

PMID- 9008276
TI  - Recombinant Coccidioides immitis complement-fixing antigen: detection of an
      epitope shared by C. immitis, Histoplasma capsulatum, and Blastomyces
      dermatitidis.
AB  - We undertook an investigation to assess the utility of a recombinant Coccidioides
      immitis complement-fixing (CF) antigen for detecting CF antibody in sera from
      patients with coccidioidomycosis. Enzyme-linked immunosorbent assays established
      that recombinant CF antigen and, for comparison, a commercially available
      coccidioidin were reactive with 19 of 19 sera from patients with active
      coccidioidomycosis. The recombinant antigen was significantly more sensitive than
      coccidioidin. The median titer obtained when patients' sera were assayed against
      recombinant CF antigen was 1:51,200 compared to 1:25,600 with coccidioidin (P <
      0.027). The recombinant antigen was also more effective in distinguishing the
      antibody levels in sera from patients with pulmonary coccidioidomycosis than in
      sera from those with disseminated disease. Whereas patients with pulmonary
      disease showed a median antibody titer of 1:25,600, those with multifocal disease
      showed a median titer of 1:102,400 (P < 0.028). The recombinant CF antigen was
      found, however, to express an epitope(s) that reacted with sera from 6 of 12
      patients with histoplasmosis and 2 of 12 patients with blastomycosis.

PMID- 9008277
TI  - Mycobacterium tuberculosis efpA encodes an efflux protein of the QacA transporter
      family.
AB  - The Mycobacterium tuberculosis H37Rv efpA gene encodes a putative efflux protein,
      EfpA, of 55,670 Da. The deduced EfpA protein was similar in secondary structure
      to Pur8, MmrA, TcmA, LfrA, EmrB, and other members of the QacA transporter family
      (QacA TF) which mediate antibiotic and chemical resistance in bacteria and yeast.
      The predicted EfpA sequence possessed all transporter motifs characteristic of
      the QacA TF, including those associated with proton-antiport function and the
      motif considered to be specific to exporters. The 1,590-bp efpA open reading
      frame was G+C rich (65%), whereas the 40-bp region immediately upstream had an
      A+T bias (35% G+C). Reverse transcriptase-PCR assays indicated that efpA was
      expressed in vitro and in situ. Putative promoter sequences were partially
      overlapped by the A+T-rich region and by a region capable of forming alternative
      secondary structures indicative of transcriptional regulation in analogous
      systems. PCR single-stranded conformational polymorphism analysis demonstrated
      that these upstream flanking sequences and the 231-bp, 5' coding region are
      highly conserved among both drug-sensitive and multiply-drug-resistant isolates
      of M. tuberculosis. The efpA gene was present in the slow-growing human pathogens
      M. tuberculosis, Mycobacterium leprae, and Mycobacterium bovis and in the
      opportunistic human pathogens Mycobacterium avium and Mycobacterium
      intracellular. However, efpA was not present in 17 other opportunistically
      pathogenic or nonpathogenic mycobacterial species.

PMID- 9008278
TI  - Parameters of disease progression in long-term experimental feline retrovirus
      (feline immunodeficiency virus and feline leukemia virus) infections: hematology,
      clinical chemistry, and lymphocyte subsets.
AB  - After several years of latency, feline immunodeficiency virus (FIV) and feline
      leukemia virus (FeLV) cause fatal disease in the cat. The aim of this study was
      to determine laboratory parameters characteristic of disease progression which
      would allow a better description of the asymptomatic phase and a better
      understanding of the pathogenesis of the two infections. Therefore,
      experimentally infected cats (FIV and/or FeLV positive) and control animals were
      observed over a period of 6.5 years under identical conditions. Blood samples
      were analyzed for the following: complete hematology, clinical chemistry, serum
      protein electrophoresis, and determination of CD4+ and CD8+ lymphocyte subsets.
      The following hematological and clinical chemistry parameters were markedly
      changed in the FIV-infected animals from month 9 onwards: glucose, serum protein,
      gamma globulins, sodium, urea, phosphorus, lipase, cholesterol, and triglyceride.
      In FeLV infection, the markedly changed parameters were mean corpuscular volume,
      mean corpuscular hemoglobin, aspartate aminotransferase, and urea. In contrast to
      reports of field studies, neither FIV-positive nor FeLV-positive animals
      developed persistent leukopenia, lymphopenia, or neutropenia. A significant
      decrease was found in the CD4+/CD8+ ratio in FIV-positive and FIV-FeLV-positive
      animals mainly due to loss of CD4+ lymphocytes. In FeLV-positive cats, both CD4+
      and, to a lesser degree, CD8+ lymphocytes were decreased in long-term infection.
      The changes in FIV infection may reflect subclinical kidney dysfunction, changes
      in energy and lipid metabolism, and transient activation of the humoral immune
      response as described for human immunodeficiency virus (HIV) infections. The
      changes in FeLV infection may also reflect subclinical kidney dysfunction and, in
      addition, changes in erythrocyte and immune function of the animals. No severe
      clinical signs were observed in the FIV-positive cats, while FeLV had a severe
      influence on the life expectancy of persistently positive cats. In conclusion,
      several parameters of clinical chemistry and hematology were changed in FIV and
      FeLV infection. Monitoring of these parameters may prove useful for the
      evaluation of candidate FIV vaccines and antiretroviral drugs in cats. The many
      parallels between laboratory parameters in FIV and HIV infection further support
      the importance of FIV as a model for HIV.

PMID- 9008279
TI  - In vitro immunologic and virologic effects of interleukin 15 on peripheral blood
      mononuclear cells from normal donors and human immunodeficiency virus type 1
      infected patients.
AB  - Interleukin 15 (IL-15) is a cytokine that shares receptor subunits and functional
      activity, such as T-cell and B-cell stimulation, with IL-2. The effect of IL-2 on
      immune function and human immunodeficiency virus (HIV) viral load in HIV-infected
      patients is being actively studied. Thus, we examined how IL-15 compares with IL
      2 in several in vitro immunologic and virologic assays in order to explore
      whether a rationale exists for pursuing initial clinical therapeutic trials with
      IL-15. The effects of IL-15 on induction of lymphokine-activated killer (LAK)
      cells, gamma interferon (IFN-gamma) production from HIV-positive peripheral blood
      mononuclear cells (PBMCs), and HIV production from PBMCs were studied. Induction
      of LAK cells by IL-15 was found in eight of eight HIV-positive donors. Incubation
      of PBMCs from some donors with IL-15 (1, 10, 50, and 100 ng/ml) induced
      production of IFN-gamma. The effect of IL-15 was compared with that of IL-2 on
      HIV replication in PBMCs from five HIV-positive patients and four HIV-negative
      donors whose PBMCs were infected in vitro with HIV. Levels of HIV p24 antigen
      were moderately lower in the presence of 10 ng of IL-15 per ml than with 10 ng of
      IL-2 per ml, but they were similar for 100 and 500 ng of each cytokine per ml. In
      summary, IL-15 can induce LAK cell activity in HIV-seropositive patients and can
      stimulate IFN-gamma production from PBMCs of some donors. IL-15 stimulates levels
      of HIV production from PBMCs which are similar to or moderately lower than those
      obtained with IL-2, depending on cytokine concentration.

PMID- 9008280
TI  - Human humoral responses to antigens of Mycobacterium tuberculosis:
      immunodominance of high-molecular-mass antigens.
AB  - The selection of antigens of Mycobacterium tuberculosis for most studies of
      humoral responses in tuberculosis patients has been restricted to molecules that
      were either immunodominant in immunized animals or amenable to biochemical
      purification rather than those that were reactive with the human immune system.
      Delineation of antigens that elicit humoral responses during the natural course
      of disease progression in humans has been hindered by the presence of cross
      reactive antibodies to conserved regions on ubiquitous prokaryotic antigens in
      sera from healthy individuals and tuberculosis patients. The levels of cross
      reactive antibodies in the sera were reduced by preadsorption with Escherichia
      coli lysates, prior to studying their reactivity against a large panel of M.
      tuberculosis antigens to which the human immune system may be exposed during
      natural infection and disease. Thus, reactivity against pools of secreted,
      cellular, and cell wall-associated antigens of M. tuberculosis was assessed by an
      enzyme-linked immunosorbent assay (ELISA). Initial results suggested that the
      secreted protein preparation contained antigens most frequently recognized by the
      humoral responses of pulmonary tuberculosis patients. The culture filtrate
      proteins were subsequently size fractionated by preparative polyacrylamide gel
      electrophoresis, characterized by reaction with murine monoclonal antibodies to
      known antigens of M. tuberculosis by an ELISA, and assessed for reactivity with
      tuberculous and nontuberculous sera. Results show that a secreted antigen of 88
      kDa elicits a strong antibody response in a high percentage of patients with
      pulmonary tuberculosis. This and other antigens identified on the basis of their
      reactivity with patient sera may prove useful for developing serodiagnosis for
      tuberculosis.

PMID- 9008281
TI  - Immunodiagnosis of alveolar echinococcosis by enzyme-linked immunosorbent assay
      using a partially purified Em18/16 enriched fraction.
AB  - An improved enzyme-linked immunosorbent assay (ELISA) system using partially
      purified Eml8/16 enriched fraction (PP-Em18/16) prepared by isoelectric focusing
      was evaluated for serodiagnosis of alveolar echinococcosis (AE). The PP-Em18/16
      ELISA was compared with Em2plus-ELISA by using sera from AE and cystic
      echinococcosis (CE) patients in China, where both AE and CE are endemic; sera
      from CE patients in Australia, where only CE exists; and sera from patients with
      cysticercosis, paragonimiasis, or sparganosis in Korea, where no indigenous AE or
      CE exists. We used Em2plus-ELISA as a standard ELISA and found 24.6% (17 of 69
      specimens) cross-reactivity with sera from CE. Furthermore, some of the sera from
      paragonimiasis, sparganosis, and cysticercosis patients were also cross-reactive
      in the Em2plus-ELISA. When we tested for similar cross-reactivity in the same
      sera from CE patients by PP-Em18/16-ELISA (23.2%, 16 of 69), it became evident
      that the specificity of the PP-Em18/16-ELISA was better than that of the Em2plus
      ELISA, since no sera from patients with the examined parasitic diseases except CE
      showed cross-reactivity. Some CE patients from China showed exceptionally high
      levels of antibody in comparison with those of CE patients from Australia, where
      no AE occurs. It is speculated that these patients with strongly positive cases
      of CE from China may have been exposed to both species of Echinococcus.

PMID- 9008282
TI  - PCR-restriction fragment length polymorphism analysis of the ospC gene for
      detection of mixed culture and for epidemiological typing of Borrelia burgdorferi
      sensu stricto.
AB  - Restriction fragment length polymorphism (RFLP) analysis of the outer surface
      protein C (ospC) gene amplicon was used for rapid screening for genetic
      variability within Borrelia burgdorferi sensu stricto species and for detection
      of multiple borreliae in culture. Primers for the ospC gene amplified a fragment
      of about 600 bp from Borrelia cultures. After cleavage of the amplified products
      by MboI and DraI, eight different RFLP types were found among 13 B. burgdorferi
      sensu stricto strains from various sources and geographical areas, and three RFLP
      types were found among 10 representative isolates from skin biopsy specimens
      taken from patients residing on the eastern end of Long Island, New York (B. W.
      Berger, R. C. Johnson, C. Kodner, and L. Coleman, J. Clin. Microbiol. 30:359-361,
      1992). These results suggested that the DNA organization of B. burgdorferi sensu
      stricto is heterogeneous not only globally but also within a localized
      geographical area and that the ospC-based typing approach could differentiate the
      B. burgdorferi sensu stricto. From the results obtained using mixed cultures of
      two different RFLP types of B. burgdorferi sensu stricto, contamination of at
      least 0.5% of different types of Borrelia cells in culture could be detected.
      This method could detect a multiple-B. burgdorferi sensu stricto infection in the
      bladders of mice experimentally infected with two different RFLP type strains.
      The present study showed that RFLP analysis of ospC-PCR products is a reliable
      method for epidemiological typing of B. burgdorferi sensu stricto and could be
      used for rapid detection of mixed Borrelia culture and multiple B. burgdorferi
      sensu stricto infections in animals, ticks, and patients.

PMID- 9008284
TI  - A simplified method for Ca2+ flux measurement on isolated human B cells that uses
      flow cytometry.
AB  - A method for Ca2+ flux measurement on isolated human peripheral B cells that uses
      flow cytometry is described. B cells were isolated by anti-CD19 magnetic bead
      sorting, and Ca2+ flux was measured with the fluo-3 reagent on a standard single
      laser flow cytometer. The response of B-cell stimulation by anti-immunoglobulin B
      (anti-IgM), anti-IgD, protein A, concanavalin A, and ionomycin was determined.
      Percentage of responder B cells, the level of Ca2+, and the time of peak
      stimulation were measured. Bound anti-CD19 monoclonal antibody coupled with small
      paramagnetic particles did not affect Ca2+ flux. All the isolated B cells
      responded maximally at 10s with stimulation by 8 microg of ionomycin. The average
      isolated preparation contains 70% IgM+ and 85% IgD+ cells, all of which showed
      peak stimulation with 10 microg of anti-IgM and anti-IgD per ml, respectively, at
      30s. Only at high concentrations of 80 microg/ml, concanavalin A produced a
      slower response, peaking at 90 s after stimulation. Stimulation with 20 microg of
      protein A per ml resulted in Ca2+ flux in only 40 to 60% of cells that had a
      rapid response and maximal stimulation resembling the pattern of activation of
      ionomycin. B cells from three patients with mixed cryoglobulinemia with high
      concentrations of monoclonal rheumatoid factors showed stimulation with
      aggregated IgG, whereas those from healthy control subjects did not,
      demonstrating the applicability of the methodology to detection of specific
      antigen stimulation of B cells. This methodology may be useful in testing the
      functional capacity of B cells in a variety of diseases. The methodology may also
      prove useful in studying antigen-specific B-cell responses when they involve a
      significant percentage of B cells.

PMID- 9008283
TI  - Relation of impaired lymphocyte proliferative function to other major human
      immunodeficiency virus type 1-induced immunological changes.
AB  - Human immunodeficiency virus (HIV) type 1 (HIV-1) induces impairment of immune
      function reflected in reduced lymphocyte proliferative responses. Many other
      immune changes are induced by HIV-1, but their relationship to lymphocyte
      functional defects is not known. The present study was designed to correlate
      functional defects with other HIV disease parameters. Cryopreserved samples from
      118 HIV-1-positive subjects and 40 seronegative individuals were examined. The
      main findings were that impaired proliferative responses to mitogens correlated
      with (i) decreased cell surface expression of the interleukin-2 receptor (CD25),
      (ii) increased expression of HLA-DR antigens on CD4 cells, (iii) reduced CD4 and
      increased CD8 cell numbers, and (iv) increased levels of serum immune complex
      dissociated p24 antigen. However, impaired function was not associated with
      increased serum neopterin, beta2-microglobulin, or soluble interleukin-2 receptor
      or with CD38 antigen expression on lymphocytes. In summary, proliferative
      functional impairment correlated with some, but not all, immunological changes
      associated with HIV-1 infection. Most of the phenotypic markers that correlated
      with altered function are cell surface molecules with significant roles in
      lymphocyte proliferation and were associated primarily with CD4 cells, compatible
      with the view that dysregulation of CD4 cells is responsible for impaired
      function.

PMID- 9008285
TI  - Diagnosis of human immunodeficiency virus type 1 infection in infants by immune
      complex dissociation p24 assay.
AB  - Using immune complex dissociation (ICD), we retrospectively examined serum and
      plasma of 206 infants aged 0 to 4 months who were perinatally exposed to human
      immunodeficiency virus (HIV). All samples were analyzed in a blinded manner.
      Infection status was determined based on the results of HIV culture and Centers
      for Disease Control and Prevention classification. The overall diagnostic
      sensitivity of the assay was 59% (93 samples, 73 infants), and specificity was
      100% (160 samples, 133 infants). When the samples were analyzed according to age,
      sensitivity was highest at age 1 to 2 months (17 of 21 infants, 81%).
      Sensitivities at other ages were 53% at < 1 month, 55% at 2 to 3 months, and 48%
      at 3 to 4 months (9 of 17, 11 of 20, and 12 of 25 cases, respectively). In 11
      evaluable cases there was a possible correlation of p24 antigen quantitation (in
      picograms per milliliter) with disease progression. We conclude that, as
      determined in this study, the ICD p24 is a rapid diagnostic assay for HIV
      infection with a sensitivity of >80% at 1 to 2 months of age and 100%
      specificity, as evaluated, up to 4 months of age.

PMID- 9008286
TI  - Novel compound tetra-, dinucleotide microsatellite polymorphism in the tumor
      necrosis factor/lymphotoxin locus.
AB  - A polymorphic (TGCG)n, tetranucleotide repeat was discovered juxtaposed to the
      (GT)n dinucleotide repeat that comprises the tumor necrosis factor a
      microsatellite (TNF) located telomeric to the tumor necrosis factor/lymphotoxin
      gene cluster. The degree of complexity of this compound tetra-,dinucleotide
      microsatellite consists of 16 potential alleles of combined length ranging from
      24 to 54 bp. The pattern of frequencies of individual alleles belonging to the
      compound TNFa microsatellite was established from 52 healthy volunteers and was
      found to be highly heterogeneous. The data diverges significantly from previously
      published statistics that recognized only a simple variable dinucleotide tandem
      repeat. The newly recognized compound tetra-, dinucleotide TNFa microsatellite
      polymorphism establishes a more accurate genetic basis to explore potential
      linkage with disease susceptibility genes located within this region of the class
      III major histocompatibility complex. In addition, variable tumor necrosis factor
      and lymphotoxin production may reflect the more complex polymorphic nature of
      this microsatellite region. Finally, compound microsatellites probably exist
      elsewhere, throughout the human genome. Recognition of their presence may have a
      considerable impact on the validity of past and future microsatellite-based
      genetic analyses.

PMID- 9008287
TI  - Correlation of seroreactivity with response to antibiotics in pediatric Lyme
      borreliosis.
AB  - Response to treatment with antibiotics was compared with serologic reactivity and
      clinical symptoms in a pediatric population with presumptive diagnoses of Lyme
      borreliosis. The population analyzed for this study consisted of a subset of a
      larger Lyme clinic population being monitored as part of a prospective study on
      pediatric Lyme borreliosis. All patients resided in an area in which Ixodes
      scapularis and Borrelia burgdorferi are considered endemic. Serum from patients
      was tested by enzyme-linked immunosorbent assay and Western blotting. Response to
      antibiotics was evaluated by members of a pediatric Lyme clinic. Results showed
      that positive serologic test results correlate with a favorable response to
      antibiotics, as does the presence of erythema migrans (EM), regardless of
      serologic status. Seronegative patients without EM had chronic fatigue and
      arthralgia and/or myalgia as primary symptoms and did not respond to antibiotics,
      even when multiple courses of treatment were given. These results indicate that
      serologic tests designed to have high specificity can reliably rule out Lyme
      borreliosis in patients with chronic symptoms, thus preventing unnecessary
      treatment with antibiotics.

PMID- 9008288
TI  - CD4+ T-cell lymphopenia in Q fever endocarditis.
AB  - Valvular endocarditis is the most serious complication of chronic Q fever, an
      infectious disease due to Coxiella burnetii. Although its pathogenesis is poorly
      understood, the role of the immune system has been evoked. The aim of this study
      was to investigate lymphocyte subsets in the peripheral blood of infected
      patients by analyzing the distribution of T- and B-lymphocyte subsets. Since
      various infectious diseases have been found to be associated with modified
      antigen expression, we also measured the antigen density of the main lymphocyte
      markers by quantitative flow cytometry. The absolute values of CD3+ T cells and
      CD19+ B cells were lower in infected subjects than in controls. The decrease in
      the CD4+ T-cell count was more pronounced than that in the CD8+ T-cell count,
      leading to a significantly lower CD4/CD8 ratio in patients. The decreases in CD4+
      T cells and CD19+ B cells were correlated with levels of C. burnetii-specific
      immunoglobulin G, showing that CD4+ lymphopenia is related to the activity of
      chronic Q fever. Quantitation of antigen expression on lymphocytes showed that
      CD3, CD4, CD8, and CD19 were expressed similarly in patients and controls. In
      contrast, CD2 and CD11a expression levels, which are both related to naive and
      memory phenotypes, were modified in patients. The study of CD45RO and CD45RA
      expression by CD4+ T cells provided evidence that lymphopenia preferentially
      affected unprimed lymphocytes.

PMID- 9008289
TI  - Vitamin A levels and human immunodeficiency virus load in injection drug users.
AB  - Although low plasma vitamin A levels are associated with increased mortality and
      higher vertical transmission during human immunodeficiency virus (HIV) infection,
      it is unknown whether plasma low vitamin A levels are a marker for circulating
      HIV load. We conducted a cross-sectional study within a prospective cohort study
      of injection drug users in order to evaluate the relationship between plasma
      vitamin A levels and HIV viral load. Plasma vitamin A level was measured by high
      performance liquid chromatography. Infectious viral load was measured by
      quantitative microculture of serial fivefold dilutions of 10(6) peripheral blood
      mononuclear cells. A total of 284 HIV-infected adults (79 women, 205 men) were
      studied. Plasma vitamin A levels consistent with deficiency were found in 28.9%
      of adults. A total of 38.0% of women and 25.3% of men had vitamin A deficiency (P
      < 0.04). The median infectious viral load for the entire study population was 8
      infectious units per million cells. No significant relationship between plasma
      vitamin A levels and infectious viral load was observed in these injection drug
      users. This study suggests that there is no correlation between HIV viral load
      and plasma vitamin A levels in injection drug users, and these variables may
      represent independent risk factors during HIV infection. HIV-infected adult women
      appear to be at higher risk of developing vitamin A deficiency.

PMID- 9008291
TI  - Antibody production against hepatitis C virus core and nonstructural 3 proteins
      is highly sensitive to deficits in T-cell function.
AB  - The influence of suppression of CD4+ and CD8+ T cells on the humoral responses to
      hepatitis C virus (HCV) core and nonstructural 3 proteins was studied. An
      increasing viral burden cannot substitute for the lack of functional T cells in
      maintaining humoral HCV-specific responses.

PMID- 9008290
TI  - Reconstruction of the immune system after unrelated or partially matched T-cell
      depleted bone marrow transplantation in children: functional analyses of
      lymphocytes and correlation with immunophenotypic recovery following
      transplantation.
AB  - Reconstitution of the immune system following T-cell-depleted bone marrow
      transplantation (BMT) in children has yet to be fully elucidated. Thus, we
      prospectively studied the recovery of immune function in 64 children who
      underwent T-lymphocyte-depleted marrow transplants using either matched family
      member donors or matched unrelated donors. We measured in vitro
      posttransplantation proliferative responses to phytohemagglutinin (PHA),
      concanavalin A, pokeweed mitogen, and Candida albicans antigen and assessed
      unidirectional allogeneic mixed-lymphocyte culture (MLC) responses at various
      times. A total of 129 healthy individuals served as normal controls for these
      assays. Responses to T-cell mitogens normalized within 12 months
      posttransplantation, while MLC responses normalized by 9 months. The presence of
      graft-versus-host disease (grade II or greater) and cytomegalovirus infection was
      associated with delays in immune function recovery. Importantly, immune function
      recovery correlated temporally with a rise in peripheral lymphocyte count. In
      contrast, the CD4/CD8 ratio was not predictive of immune recovery. Knowledge of
      immune function recovery may guide clinicians in devising strategies to minimize
      the risk of infection post-BMT.

PMID- 9008292
TI  - Cytomegalovirus glycoprotein B-specific antibody analysis using
      electrochemiluminescence detection-based techniques.
AB  - An electrochemiluminescence technique was used to develop versatile and sensitive
      assay strategies for determination of seroreactivities against biologically
      important cytomegalovirus neutralization epitopes expressed on glycoprotein B.
      Indirect binding assays showed wide linear assay ranges and revealed that serum
      samples diluted in parallel with a monoclonal antibody-based standard,
      simplifying quantitative analytical assessments.

PMID- 9008294
TI  - Primary structure of mannuronate lyases SP1 and SP2 from Turbo cornutus and
      involvement of the hydrophobic C-terminal residues in the protein stability.
AB  - The complete amino acid sequences of two isoforms, SP1 and SP2, of mannuronate
      lyase from a wreath shell, Turbo cornutus, were determined to elucidate amino
      acid residues responsible for causing the more stable protein conformation of
      SP2. The sequences of the two isoforms were identical except for two hydrophobic
      C-terminal amino acid residues of SP2, Ile and Leu, which were additionally
      attached to Thr of the C-terminal residue of SP1 (253 residues in total). The
      molecular weight of SP2 was calculated to be 28,912 from the amino acid sequence
      data. Two disulfide bond cross-linkages were found to be between 106 and 115 and
      between 145 and 150, and a partially buried single SH group was located at 236. A
      carbohydrate chain that consisted of 3 GlcNAc, 3 Fuc, and 1 Man was anchored on
      Asn-105 in a typical carbohydrate-binding motif of Asn-X-Ser. This is the first
      evidence of the primary structure of mannuronate lyase, and no significant
      homology of the amino acid sequence among other proteins was found. The C
      terminal truncated SP2, which was produced by digestion with carboxypeptidase Y
      and corresponded structurally to SP1, showed a thermal stability identical to
      that of SP1. These results indicate that the higher stability of SP2 than SP1
      arises from the presence of the C-terminal two hydrophobic amino acid residues.

PMID- 9008293
TI  - The essentiality of calcium ion in the enzymatic activity of Taiwan cobra
      phospholipase A2.
AB  - In order to address the mechanism whereby Ca2+ wad crucial for the manifestation
      of the enzymatic activity of phospholipase A2 (PLA2), four divalent cations were
      used to assess their influences on the catalytic activity and the fine structures
      of Naja naja atra PLA2. It was found that substitution of Mg2+ or Sr2+ for Ca2+
      in the substrate solution caused a decrease in the PLA2 activity to 77.5% or
      54.5%, respectively, of that in the presence of Ca2+. However, no PLA2 activity
      was observed with the addition of Ba2+. With the exception of Mg2+, the
      nonpolarity of the 8-anilinonaphthalene-1-sulfonate (ANS)-binding site of PLA2
      markedly increased with the binding of cations to PLA2. In the meantime, the
      accessibilities of Lys-6 (65) and Tyr-3 (63) toward trinitrobenzene sulfonate and
      p-nitrobenzenesulfonyl fluoride were enhanced by the addition of Ca2+, Sr2+, and
      Ba2+, but not by Mg2+. The order of the ability of cations to enhance the ANS
      fluorescence and the reactivity of Lys and Tyr residues toward modified reagents
      was Ba2+ > Sr2+ > Ca2+ > Mg2+, which was the same order as the increase in their
      atomic radii. These results, together with the observations that the ANS molecule
      binds at the active site of PLA2 and that Tyr-3, Lys-6, and Tyr-63 of PLA2 are
      involved in the binding with the substrate, suggest that the binding of Ca2+ to
      PLA2 induces conformational changes at the active site and substrate-binding
      site. However, the smaller atomic radius with Mg2+ or the bigger atomic radii
      with Sr2+ and Ba2+ might render the conformation improperly rearranged after
      their binding to PLA2 molecule.

PMID- 9008295
TI  - A vector projection method for predicting supersecondary motifs.
AB  - For the 11 types of most frequently occurring supersecondary motifs, we used a
      new method--the vector projection method--to predict a protein's supersecondary
      structure. In a training set of peptides and a test set of peptides we obtained a
      satisfactory result, with a prediction accuracy of about 90%. The high prediction
      accuracy indicates that this method is reasonable for predicting the folding
      motifs of proteins. This work provides insight into the problem of predicting a
      protein's local structure accurately, and is of particular value in protein
      modeling, prediction, and molecule design.

PMID- 9008296
TI  - Stability and folding of a mutant ribose-binding protein of Escherichia coli.
AB  - A mature mutant ribose-binding protein (RBP) of Escherichia coli was obtained by
      site-directed mutagenesis, replacing Thr-3 in the N-domain of wild-type mature
      RBP (WT-mRBP) with a Trp residue (N-Trp-mRBP). The equilibrium unfolding
      properties and the refolding kinetics of this protein were monitored by
      fluorescence and circular dichroism (CD). The stability of N-Trp-mRBP appears to
      be the same as that of C-Trp-mRBP, another mutant obtained by replacing Phe-187
      with a Trp, and lower than that of WT-mRBP. The overall refolding rate of N-Trp
      mRBP is much smaller than that of C-Trp-mRBP, which, in turn, is similar to that
      of WT-mRBP. For the case of WT-mRBP, the rate constant obtained by Tyr
      fluorescence is identical to the value obtained by CD. But with C-Trp-mRBP, the
      rate constant from CD is smaller than the value from the Trp fluorescence and
      this difference in the rate constants is much greater with the N-Trp-mRBP.

PMID- 9008297
TI  - Conversion of cysteinyl residues to unnatural amino acid analogs. Examination in
      a model system.
AB  - Improved and efficient techniques have led to an explosive growth in the
      application of site-directed mutagenesis to the study of enzymes. However, the
      limited availability of only those 20 amino acids that are translated by the
      genetic code has prevented the systematic variation of an amino acid's properties
      in order to define more precisely its role in the catalytic mechanism of an
      enzyme. An approach is being examined that combines the high specificity of site
      directed mutagenesis with the flexibility of chemical modification to overcome
      these limitations. A set of reagents has been synthesized and reacted with a
      cysteine model to produce a series of amino acid structural analogs at
      appreciable rates and in good overall yields. The selective incorporation of
      these analogs in place of important functional amino acids in a protein will
      allow a more detailed examination of the role of that amino acid.

PMID- 9008299
TI  - State of aggregation of recombinant hirudin in solution under physiological
      conditions.
AB  - The state of aggregation of recombinant desulfatohirudin (r-HV1) in solution
      under physiological conditions (pH 7.5, 0.15 N NaCl) was investigated by
      sedimentation equilibrium. The weight-average molecular weight MW determined by
      sedimentation equilibrium was found to be 6914 +/- 76 Da compared to 6964 Da
      expected from the amino acid sequence. The MZ/MW ratio was found to be 1.03,
      which demonstrates that under the conditions studied hirudin exists in solution
      as a monomer. This result is in agreement with the relative molecular weight (M,)
      of recombinant hirudin variant 3 reported by Otto and Seckler [(1991), Eur. J.
      Biochem. 202, 67-73], who also used equilibrium ultracentrifugation, but not with
      the molecular weight estimated from gel permeation chromatography of natural
      hirudin (51,300 Da) [Konno et al. (1988), Arch. Biochem. Biophys. 267, 158-166].
      Knowledge of the state of aggregation is essential for understanding the
      mechanism of interaction of thrombin and hirudin under physiological conditions.

PMID- 9008298
TI  - Isolation and rapid sequence characterization of two novel bovine beta
      lactoglobulins I and J.
AB  - Two novel bovine beta-lactoglobulins I and J have been isolated from bovine milk
      and characterized by isoelectric focusing. Their primary structure was determined
      by a very rapid method consisting of a combination of Edman sequencing, mass
      analysis, and ladder sequencing by mass spectrometry. We found that both new beta
      lactoglobulins are of the bovine beta-lactoglobulin B-variant type. beta
      lactoglobulin I shows Gly instead of Glu at position 108, whereas beta
      lactoglobulin J shows a Pro-to-Leu exchange at position 126.

PMID- 9008300
TI  - cDNA sequence analysis and mutagenesis studies on the A chain of beta
      bungarotoxin from Taiwan banded krait.
AB  - The cDNA encoding the A chain of beta-bungarotoxin (beta-Bgt) was constructed
      from the cellular RNA isolated from the venom glands of Bungarus multicinctus
      (Taiwan banded krait). The deduced amino acid sequence encoding the A chain
      revealed that the determined chain was different from the known A chains (A1, A2,
      A3, A4, and A5). Nevertheless, the amino acid sequence and the cDNA sequence of
      the novel A chain were highly homologous with those of other A chains. The gene
      encoding the A chain of beta-Bgt was subjected to mutagenesis, and the Tyr-11,
      Cys-15, and Leu-72 of the A chain were substituted by Cys-11, Ser-15, and Cys-72,
      respectively. Instead of the six disulfide bonds observed with the A chain, the
      resulting mutant contained seven disulfide linkages in its molecular structure
      which simulated those of presynaptic PLA2 neurotoxins and PLA2 enzymes. However,
      the mutant did not exhibit a higher phospholipase activity than that noted with
      the recombinant A chain. These results seem to suggest that, in the absence of
      the B chain, the six pairs of disulfide bonds in the recombinant A-chain molecule
      are enough to maintain its active conformation for exerting the phospholipase
      activity.

PMID- 9008302
TI  - Prediction of the secondary structure content of globular proteins based on
      structural classes.
AB  - The prediction of the secondary structure content (alpha-helix and beta-strand
      content) of a globular protein may play an important complementary role in the
      prediction of the protein's structure. We propose a new prediction algorithm
      based on Chou's database [Chou (1995), Proteins Struct. Funct. Genet. 21, 319].
      The new algorithm is an improved multiple linear regression method, taking the
      nonlinear and coupling terms of the frequencies of different amino acids into
      account. The prediction is also based on the structural classes of proteins. A
      resubstitution examination for the algorithm shows that the average errors are
      0.040 and 0.033 for the prediction of alpha-helix content and beta-strand
      content, respectively. The examination of cross-validation, the jackknife
      analysis, shows that the average errors are 0.051 and 0.044 for the prediction of
      alpha-helix content and beta-strand content, respectively. Both examinations
      indicate the self-consistency and the extrapolative effectiveness of the new
      algorithm. Compared with the other methods available currently, our method has
      the merits of simplicity and convenience for use, as well as a high prediction
      accuracy. By incorporating the prediction of the structural classes, the only
      input of our method is the amino acid composition of the protein to be predicted.

PMID- 9008301
TI  - Initial characterization of autoprocessing and active-center mutants of CMV
      proteinase.
AB  - Human cytomegalovirus (CMV) encodes a unique serine proteinase that is required
      in the maturation of the viral capsid. The CMV proteinase can undergo
      autocatalytic activation and is subject to proteolytic self-inactivation. Mutant
      enzyme forms were prepared to eliminate the initial autoprocessing site and thus
      form an active single-chain protein for structure-function studies. Two mutants
      of CMV proteinase were cloned and expressed in Escherichia coli. The A143V mutant
      was a conservative substitution at the first internal cleavage site. The S132A
      mutant modified one of the triad of residues responsible for catalytic activity.
      Through the use of computer-controlled high-cell-density fermentations the mutant
      proteins were expressed in E. coli at approximately 170 mg/L as both soluble
      (approximately 40% of total) and inclusion-body forms (approximately 60% of
      total). The soluble enzyme was purified by standard methods; inclusion-body
      protein was isolated by standard methods after refolding and solubilization in
      guanidine or urea. Sedimentation equilibrium and sedimentation velocity analyses
      reveal that the enzyme undergoes concentration-dependent aggregation. It exhibits
      a monomer <==> dimer equilibrium (Kd = 1 microM) at low concentrations and
      remains dimeric at high concentrations (28 mg/ml). Differential scanning
      calorimetry data for protein thermal unfolding fit best to a non-two-state model
      with two components (Tm = 52.3 and 55.3 degrees C) which subsequently aggregate
      upon unfolding. Analysis of the short-UV circular dichroism spectra of protein
      forms resulting from expression as soluble molecules (not refolded) reveals that
      the two mutants have very similar secondary structures which comprise a mixed
      structural motif of 20% alpha-helix, 26% beta-sheet, and 53% random coil. Though
      soluble and active (A143V mutant only), CD analysis revealed that protein
      refolded from inclusion bodies did not exhibit spectra identical to that of
      protein expressed only in soluble form.

PMID- 9008303
TI  - Functional significance of polymorphism among MHC class II gene promoters.
AB  - The functional significance of polymorphism among MHC class II promoters in man
      and mouse is here reviewed, mainly in terms of the hypothesis of differential
      expression. The hypothesis proposes that differences between antigen-presenting
      cells in MHC class II expression exert a co-dominant effect on the Th1-Th2
      cytokine balance, such that class II molecules of one type come to control to a
      greater extent the production of one group of cytokines, and those of another
      type the production of the alternative group. The survey deals with the influence
      of signal strength and antigen-presenting cell type on T-cell subset
      differentiation; functional differences between MHC class II molecules not
      obviously related to determinant selection; disease protection mediated by HLA
      alleles; mechanisms possibly responsible for allotypic and isotypic bias;
      overdominance (heterozygous advantage) in selection for expression of class II
      alleles; MHC class II promoter structure and function; inter-locus and inter
      allele variability within human MHC class II gene upstream regulatory regions; a
      comparison of these polymorphisms in mouse and man; read-out of class II promoter
      function; and a comparison with expression of MHC class I. We conclude that the
      evidence that this variation is functionally active (i.e. controls expression) is
      increasing, but is not yet compelling. The crucial test still to come, we
      suggest, is whether or not the biological effects attributable to this
      polymorphism will line up with molecular studies on expression.

PMID- 9008304
TI  - Stimulation through CD50 (ICAM-3) induces both activation and programmed cell
      death of human thymocytes.
AB  - CD50 (ICAM-3) has been identified as the third CD11a/CD18 (LFA-1) counter
      receptor. We investigated the expression and possible role of this molecule in
      the induction of early and late activation events in human thymocytes. We
      observed that CD50 expression is acquired by early T cell progenitors (CD34+) and
      maintained during thymic development, reaching the highest levels in the most
      mature population of thymocytes (CD3high). Neither basal nor cytokine-induced
      expression of CD50 was observed on untransformed human thymic epithelial cell
      lines. Cross-linking of CD50 expressed on the surface of human thymocytes, by
      using mAbs recognizing epitopes not related to the CD11a binding site, transduced
      transmembrane signals leading to an increase of intracellular calcium
      concentration. This calcium mobilization was inhibited when CD50 was co-cross
      linked with CD45, suggesting that tyrosine phosphorylation is also involved in
      CD50 signaling. The same anti-CD50 mAbs that were able to affect intracellular
      calcium levels were shown to induce CD69 but not CD25 expression on human
      thymocytes. This effect was preferentially observed on CD3low/CD3high thymocyte
      subpopulations. Cross-linking of CD50 also significantly increased activation
      induced cell death of human thymocytes. These results support the idea that CD50
      molecule can play a role in developing functionally mature T lymphocytes.

PMID- 9008305
TI  - African-American HLA class II allele and haplotype diversity.
AB  - Molecular genetic techniques were used to type nine loci in the HLA class II
      region in 241 unrelated African-Americans from New York City (NYC). Several
      effects attributable to recent genetic admixture were evident: the number of
      distinct class II alleles and haplotypes was larger in the African-Americans than
      in people of African or European origin, the allele frequencies were more
      consistently even, and linkage disequilibrium was present across the entire class
      II region. The African-American DRB1 allele frequencies almost always fell
      between frequencies among samples from northern Europe and the Gambia, two
      possible founding populations. The exceptions are attributed to the contribution
      of other genetically dissimilar African groups to the African-American gene pool.
      DRB1 allele frequencies (specifically DRB1*1501) and some haplotypes of DRB1-DPB1
      were different in our NYC and the 11th International Histocompatibility Workshop
      (IHW) samples of African-Americans. The high level of allele and haplotype
      diversity found in African-Americans has important implications for the
      construction of pools of unrelated potential donors for tissue transplantation.

PMID- 9008306
TI  - Significance of antibodies to streptococcal M protein in psoriatic arthritis and
      their association with HLA-A*0207.
AB  - Psoriatic arthritis (PA) is an immune disease associated with HLA-A2 in the
      Japanese population. To investigate mechanisms the association between HLA-A2 and
      PA, we examined in vivo immune responsiveness to Streptococcus pyogenes.
      Recombinant M proteins for the subtype specific N-terminal half (AB region) and
      conserved C-terminal half (C region) were produced separately. IgG antibody level
      against each region was measured by ELISA in 31 PA patients, 88 patients with
      psoriasis vulgaris, 6 patients with rheumatoid arthritis and 77 healthy controls.
      We found that IgG antibody levels against the C region were markedly higher in
      the PA patient group than in the other disease groups or controls. Further, IgG
      antibody levels were higher in PA patients with spondylitis and polyarticular
      arthritis than in PA patients with rheumatoid-like arthritis and arthritis
      mutilans. In contrast, no significant difference in the IgG antibody levels
      against the AB region was observed among the tested groups. HLA-A2 DNA typing
      showed that HLA-A*0207 was associated with PA (RR = 17.6; pcorr < 0.01) and the
      IgG antibody responses to the C region correlated well with the presence of HLA
      A*0207. These results suggest that streptococcal infection may be involved in the
      pathogenesis of PA by participating in the HLA-linked immune responsiveness.

PMID- 9008307
TI  - Inefficient assembly limits transport and cell surface expression of HLA-Cw4
      molecules in C1R.
AB  - HLA-C antigens are expressed to the cell surface at roughly 10% the level of HLA
      B or -A, and their serological definition remains persistently difficult. To
      characterize the factors limiting surface expression, the processes of assembly
      and intracellular transport of HLA-Cw4 molecules were investigated in the C1R
      cell line. When appropriate peptides were added to cultured cells or in cell
      lysates significant amounts of conformed HLA-C molecules that associate with beta
      2-microglobulin (beta 2 m) are detected, but are indeed not sufficient to restore
      expression to the level observed for HLA-A or -B molecules. Furthermore, a
      precursor/product relationship exists between the free class I heavy chain and
      the mature conformation of HLA-Cw4 molecules. Thus, HLA-C assembly promotes the
      conversion of HC-10-reactive molecules (weakly-beta 2m-associated non-ligand
      associated free HC form) into the beta 2m-associated class I molecules recognized
      by W6/32. To further investigate the factors that regulate cell surface
      expression, intracellular transport of HLA-Cw4 was studied in pulse chase
      analysis. In contrast to some HLA-A and B, maturation of HLA-Cw4 heavy chains and
      their export to the medial and trans-Golgi compartments are quite inefficient.
      After 4 h of chase period, roughly half of the pulse-labeled HLA-Cw4 molecules
      have transited to the medial-Golgi and acquired complex oligosaccharides
      characteristic of mature form. In addition, treatment with gamma-interferon does
      not appear to improve maturation of HLA-Cw4 heavy chains, suggesting that
      increased supply of peptides does not influence intracellular transport.
      Moreover, only a small fraction in the pool of HLA-Cw4 molecules was subsequently
      transported through the trans-Golgi network, as indicated by their acquisition of
      sialic acids. Taken together these studies show that HLA-Cw4 molecules are
      inefficiently transported through the Golgi apparatus and presumably retained in
      the endoplasmic reticulum or cis-Golgi compartment.

PMID- 9008308
TI  - HLA haplotypes and class II molecular alleles in Sardinian and Italian patients
      with pemphigus vulgaris.
AB  - HLA class II antigens and DRB1, DQA1, DQB1 alleles were studied in 16 Italian and
      in 16 Sardinian patients with pemphigus vulgaris (PV). In the last group the
      complete HLA A-DQ haplotypes, including the complotypes, were defined by family
      studies. As in other populations, two PV susceptibility haplotypes were found:
      HLA-DRB1*0402, DQA1*0301, DQB1*0302 and HLA-DRB1*1401, DQA1*0104, DQB1*0503. The
      first haplotype was largely prevalent in the Sardinian patients and was a part of
      the extended haplotype HLA-A2, Cw4, B35, S31, DR4, DQ8. The strength of the
      allele associations to PV is in agreement with the view that the main PV
      susceptibility genes are the DRB1*0402 and DQB1*0503 alleles. A genetic
      resistance to PV seems to be conferred by the HLA-DR3, DQ2 haplotype in the
      Sardinian population.

PMID- 9008309
TI  - MHC class II alleles and haplotypes in patients with pemphigus vulgaris from
      India.
AB  - Pemphigus vulgaris (PV) is a blistering disease of the skin and mucous membranes
      characterized by an autoantibody response against a keratinocyte adhesion
      molecule, desmoglein 3, causing acantholysis and blister formation. We compared
      high resolution MHC class II alleles and haplotype frequencies (HLA-DRB, DQA1 and
      DQB1) in 37 patients with PV to 89 haplotypes of normal relatives from New Delhi
      and Ahmedabad. We found that PV patients had significantly increased frequencies
      of DRB1*1404 (P < 0.0001), DQA1*0101 (P = 0.001), and DQB1*0503 (P < 0.0001).
      These associations were due to the increased frequencies of the haplotype HLA
      DRB1*1404, DRB3*0202, DQA1*0101, DQB1*0503 in patients compared to control
      haplotypes (p < 0.0001). Also, patients from Ahmedabad had a significant increase
      in HLA-DQB1*0302 (p = 0.03). An identical amino acid sequence (Leu-Leu-Glu-Arg
      Arg-Arg-Ala-Glu), in positions 67-74 of the beta domain of DRB alleles is
      restricted to some DR14 alleles. Therefore, there are three possible explanations
      for class II allele involvement in autoantibody in PV patients with class II
      haplotypes marked by HLA-DR14. First, the class II alleles could be markers for
      an unidentified susceptibility gene in linkage disequilibrium with them. Second,
      the primary association could be with DQB1*0503 and the association with HLA-DR14
      alleles would be the result of linkage disequilibrium. Third, the HLA-DRB1 locus
      susceptibility could involve a specific amino acid sequence in the third
      hypervariable region shared by several HLA-DR14 alleles.

PMID- 9008310
TI  - HLA-A*02 subtype distribution in Caucasians from northern Italy: identification
      of A*0220.
AB  - This study describes a comprehensive easy to perform PCR-SSOP typing approach
      suitable for complete genomic subtyping of HLA-A*02. A single 1.6 kb PCR
      amplificate spanning exons 2, 3 and 4 of the HLA-A*02 gene was used for
      hybridization with a panel of twenty-four SSOPs. This allowed unequivocal
      assignment of all so far known HLA-A2 subtypes, including A*0209 and A*0215N
      which differ for nucleotide substitutions in exon 4, without the need for two
      separate amplifications. Using this approach, HLA-A*02 subtype distribution was
      analyzed in 218 samples from unrelated, healthy individuals from northern Italy
      enrolled in the Italian Bone Marrow Registry and typed as HLA-A2 by serology or
      generic molecular analysis. As expected, A*0201 was found in the majority (92.6%)
      of samples. However, a significant number (6.8%) of individuals carried A*0205.
      Furthermore, A*0202, A*0208, A*0209 and A*0217, so far not described in
      Caucasians, were detected in a low number of samples (frequency ranging from
      0.45% to 1.8%). Finally, a novel HLA-A*02 subtype, A*0220, was detected in 0.9%
      of the samples. As confirmed by DNA sequencing of exons 2 and 3, this allele is
      identical to A*0201 except for a single nucleotide substitution in codon 66 which
      changes the predicted amino acid sequence form Lys to Asn. The findings of this
      study have implications for the selection of HLA-A*02+ donors in unrelated bone
      marrow transplantation and of patients for specific immuno-therapy with HLA-A*02
      restricted peptide vaccines.

PMID- 9008311
TI  - High resolution HLA-C typing by PCR-SSP: identification of allelic frequencies
      and linkage disequilibria in 604 unrelated random UK Caucasoids and a comparison
      with serology.
AB  - Recent evidence indicates that HLA-C molecules are biologically relevant by
      eliciting T-cell responses and exerting control over NK cell function. In
      addition, HLA-C is associated with susceptibility to various diseases, notably
      psoriasis vulgaris. Clarification of the full biological roles for HLA-C has
      however proved difficult because detection of HLA-C antigens by complement
      mediated cytotoxicity using alloantisera is inefficient. Up to 50% of individuals
      in every race have serologically undetectable HLA-C locus antigens due to a
      combination of relatively low expression, lack of serological reagents and a lack
      of information about the distribution of the HLA-C blank alleles. Recently,
      amplification of DNA using sequence-specific primers (PCR-SSP) has proved a
      reliable, accurate and rapid method for medium resolution HLA-C typing. We have
      now developed high resolution HLA-C typing by PCR-SSP utilizing allele and group
      specific PCR-SSP reactions which can identify all HLA-C alleles (except non
      coding change alleles) in most heterozygous combinations. Using this system we
      have typed 604 unrelated United Kingdom Caucasoids to generate accurate frequency
      and linkage disequilibrium data. To assess the validity of serology for HLA-C,
      PCR-SSP typings for 527 out of the 604 individuals were compared to serology. We
      find that the frequency of many HLA-C antigens has been underestimated by
      serology and some antigens such as Cw6 are consistently assigned incorrectly by
      serology. The overall discrepancy rate between serology and SSP was high at 37%
      (195/527). High-resolution HLA-C typing of 112 International Histocompatibility
      Workshop cell lines has also been performed.

PMID- 9008312
TI  - Molecular analysis of HLA-B in the Malaysian aborigines.
AB  - We have examined 56 unrelated individuals from Malaysian aborigines for their DNA
      polymorphism of the HLA-B gene by sequence specific oligonucleotide probe (SSO)
      method. Using the SSO hybridization, we found that one specific DNA allele with a
      B*1513 like pattern of epitope combination (ECB1513) was dominant among the
      Melayu Asli (Af = 41.9%) and the Senoi (Af = 24%). To determine the nucleotide
      sequences of ECB1513, a DNA fragment spanning from the beginning of exon 1 to the
      middle of exon 4 of the HLA-B gene was amplified by polymerase chain reaction
      (PCR) from two ECB1513 positive individuals, and the PCR products were cloned and
      sequenced. This sequencing analysis confirmed that ECB1513 was identical to HLA
      B*1513 in exon 1, 2, 3, and 4. Amino acid sequence of this major allele, HLA
      B*1513, in the aborigines especially around the peptide binding groove (B and F
      pockets), was compared with that of African B*5301 that had been suggested to
      confer resistance to malaria infection in Africa. The amino acid residues
      composing of the F pocket were completely identical in B*1513 and B*5301. These
      observations suggest that a common environmental factor, the malaria infection,
      might have independently enhanced the selection of functional change in the
      polymorphic portion of HLA-B gene in Africa and in South-East Asia.

PMID- 9008313
TI  - Molecular cloning of two new HLA-C alleles: Cw*1801 and Cw*0706.
AB  - Nucleotide sequence analysis of the HLA-C alleles of the GB92 cell line,
      heterozygous for B*8101 and B*4407, revealed the existence of two new allelic
      variants: Cw*1801 and Cw*0706. The former allele, initially detected as a PCR-SSP
      variant, displays a hybrid aspect, sharing sequence motifs with Cw*07 at exons 1
      and 2, and with Cw*04 at distal exons. In serological assays, Cw*1801 is only
      recognized by some cross-reactive sera. Cw*0706 shows a primary structure closely
      related to previously known Cw7 alleles, but carries new sequence motifs at its
      3'-end. Preliminary data indicate that Cw*1801 is associated to B*8101 and that
      Cw*0706, B*4407 could account for a part of the Cw7, B44 haplotypes observed in
      African populations.

PMID- 9008314
TI  - Unique HLA antigen frequencies in the Finnish population.
AB  - The Finnish Bone Marrow Donor Registry was established 1992 to serve Finnish
      patients in urgent need of bone marrow transplantation. This study details the
      HLA antigen frequencies, including those of the A 19 subtypes, in the Finnish
      population. Large regional variations were found in antigen frequencies between
      the different geographical areas of Finland. In particular, antigens A9, B12,
      B35, Cw4 and DR3 display regional frequency deviations, but B7, B8 and B15 also
      exhibit regional variations. The present population is the largest (n = 10,000)
      ever HLA-typed in Finland. 97% of the donors were HLA-A-B-DR typed. Confirmation
      of the serological HLA type was performed by DNA typing on 3% of the donors in
      the registry. A potential donor was found for 52% of Finnish patients in need of
      a matched unrelated donor for a bone marrow transplantation. Due to the ethnic
      origin of the Finns, it is not easy to find suitable bone marrow donors for
      Finnish patients in worldwide registries. It is thus important to maintain a
      national bone marrow donor registry which recruits donors from all over the
      country.

PMID- 9008315
TI  - A novel HLA-B allele, HLA-B*1803.

PMID- 9008316
TI  - A novel HLA-A*24 (A*2410) identified in a Javanese population.

PMID- 9008317
TI  - Identification of a new DRB1 allele (DRB1*1325) by PCR-SSP and DNA sequencing.

PMID- 9008319
TI  - Nucleotide sequence for HLA-A*0221 which encodes a novel HLA class I polymorphic
      residue.

PMID- 9008318
TI  - HLA-A* 1104: a new allele found in a Laotian family.

PMID- 9008320
TI  - Nomenclature for factors of the HLA system, update August/September 1996.

PMID- 9008321
TI  - Application of factor analysis for the determination of specific frequency bands
      in corpus cavernosum EMG power density spectra.
AB  - Corpus cavernosum electromyogram (CC-EMG) recording provides diagnostic
      information on cavernous autonomic innervation and the intact state of cavernous
      smooth muscle cells. Evaluation of these signals is time consuming and complex.
      Therefore, we attempted to facilitate their interpretation and to increase their
      objectivity by using computer-based digital signal processing. Spectral
      parameters were used as a starting point for this analysis, which were calculated
      from the Fourier-transformed time domain CC-EMGs. Factor analysis was applied to
      determine specific frequency bands in the CC-EMG power density. Two hundred power
      spectra, taken from normal subjects (n = 66) and from patients suffering from
      erectile dysfunction (n = 134), constituted the basic data. As a result of
      applying factor analysis, four specific frequency bands were depicted: 0.0-0.3,
      0.3-3.5, 3.5-6.0 and 6.0-10.0 Hz. The results of this study form the basis for
      further mathematical evaluation and calculation of the CC-EMG for clinical and
      diagnostic purposes.

PMID- 9008322
TI  - Characterization of in vitro relaxant mechanisms in erectile tissue from rabbits
      of different ages.
AB  - In the present study we investigated the in vitro relaxant response of erectile
      tissue obtained from rabbits of different ages (3, 7 and 24 months) in order to
      detect the progression with age of cavernosal activity in response to substances
      acting via endothelium-dependent or -independent mechanisms. Noradrenaline
      induced a concentration-dependent contraction (0.1 microM-3 mM), with an increase
      in the contractility in the 24-month-old group. Acetylcholine produced a
      concentration-dependent relaxant effect in the three age groups, with a reduction
      of the maximal relaxant effect in older animals. ATP (10 microM-1 mM) and
      adenosine (10 microM-1 mM) induced a concentration-dependent relaxant effect that
      was higher in the older group. The presence of the NO2-synthase inhibitor N omega
      nitro-L-arginine methyl ester (L-NAME) (0.1 mM) or of the P2-purinoceptor
      antagonist suramin did not affect ATP relaxation. Relaxation induced by sodium
      nitrite and nifedipine was reduced in older animals. In conclusion, aging
      selectively alters the in vitro responsiveness of rabbit erectile tissue.
      Purinergic system remains more active despite a decrease in the maximal
      endothelial cholinergic activity and the direct smooth muscle relaxant component.

PMID- 9008323
TI  - Chronic treatment with cyclosporine A in New Zealand rabbit: aortic and erectile
      tissue alterations.
AB  - Transplanted patients frequently present erectile impotence. In order to test any
      interference by cyclosporine A (CsA), which is commonly used in the post
      transplantation management, we investigated the in vitro contractile and relaxant
      responses of corpus cavernosum and aorta from rabbits chronically treated with
      CsA. Male New Zealand White rabbits 6 months of age were treated with CsA (25
      mg/kg per day s.c.) or solvent (corn oil) for 3 weeks. Descending thoracic aorta
      and erectile tissue were studied in vitro at the end of treatment. Isometric
      tension was recorded. In thoracic aorta, noradrenaline (0.1-30 mM) induced a
      concentration-dependent contraction with no difference between the two groups.
      Acetylcholine (30 nM-3 mM) produced relaxation (52 +/- 4% at 1 mM) that was
      significantly reduced in comparison to controls (67 +/- 4%, P < 0.05). ATP (3-10
      mM) relaxation was not significantly different (maximal 78 +/- 10% and 62 +/- 12%
      in CsA-treated and controls). The relaxation produced by sodium nitrite was
      reduced in CsA-treated rabbits (at 10 mM and 0.1 mM concentrations). In erectile
      tissue, no significant variation in the response of isolated erectile tissue to
      the above drugs was observed between CsA-treated and control animals. These data
      indicate that chronic treatment with CsA in rabbits, despite alteration of the in
      vitro response of thoracic aorta, does not directly influence the function of
      penile tissue with relaxants.

PMID- 9008324
TI  - Serum creatine kinase enzyme levels in the early diagnosis of spermatic cord
      torsion.
AB  - Delay in the diagnosis of spermatic cord torsion (SCT) is still a significant
      cause of testicular loss in children. The aim of this experimental study was to
      assess the diagnostic value of serum creatine kinase (CK) in the early period
      following SCT. Forty male rats were assigned randomly into five similar groups:
      group A, control; group B, sham, right testis exposed, manipulated, and blood
      sampling at 6th h; group C, right SCT, blood sampling at 2nd h; group D, right
      SCT, blood sampling at 4th h; and group E, right SCT, blood sampling at 6th h. Ck
      and its isoenzymes were measured in the sera of all animals. All testes were
      removed and examined histopathologically. Significant increases in serum CK
      levels compared to control and sham groups were observed at 4 and 6 h following
      SCT. The major increase in CK was observed in the CK-MM isoenzyme fraction.
      Histologic pictures showed varying degrees of edema, vascular congestion, and
      hemorrhage in the testicular tissue, but no necrosis in any of the study groups.
      These results showed that serum CK levels in rats in the early period following
      SCT increase significantly before necrosis of testicular tissue. This may be of
      value as a diagnostic test, to corroborate findings from clinical studies.

PMID- 9008325
TI  - A possible role for nitric oxide in the regulation of human ureteral smooth
      muscle tone in vitro.
AB  - There is ample evidence that nitric oxide (NO) is an important neurotransmitter
      in many tissues of the urogenital tract. The aim of the present study was to
      examine the possible role of NO in ureteral relaxation. Human ureteral rings were
      mounted in organ bath chambers and precontracted in KCl. Increasing doses of the
      NO donor linsidomine (SIN-1) were added with and without prior blockade of the
      NO/cGMP pathway by methylene blue and protein kinase (PK) inhibitors Rp-8-pCPT
      cGMPS and RP-8-CPT-cAMPS. Electrical filed stimulation (EFS) was done before and
      after incubation with L-NOARG (NG-nitro-L-arginine) and TTX (tetratodoxin). For
      detection of neuronal NO synthase (NOS), ureters were stained
      immunohistochemically. Ureteral strips were dose dependently relaxed by SIN-1;
      preincubation with methylene blue and protein kinase G inhibitor significantly
      reduced the SIN-1-induced relaxations. No effects of L-NOARG and TTX on EFS
      induced tone alterations were found. NOS-positive neuronal axons and nerve-ending
      like structures were found in the muscular layers. Our in vitro findings suggest
      that ureteral relaxation may involve the NO pathway.

PMID- 9008326
TI  - Ureterovesical junction inhibitory reflex and vesicoureteral junction excitatory
      reflex: description of two reflexes and their role in the ureteric antireflux
      mechanism.
AB  - The purpose of this study was to investigate the response of the ureterovesical
      junction (UVJ) to ureteric distension and to bladder filling with the aim of
      elucidating the mechanism of UVJ antireflux. The study was performed on 13
      healthy volunteers [age 41.4 +/- 10.2 (SD) years; nine men, four women]. A
      ureteric catheter connected to a pressure transducer was introduced into the
      ureter proper. After recording the ureteric pressure, the catheter was withdrawn
      to the bladder, and the resting pressures in the UVJ and bladder were registered.
      The catheter was positioned in the UVJ and a 3F balloon-tipped ureteric catheter
      was introduced into the ureter proper and filled saline in increments of 1 ml.
      The pressure response of the ureter and UVJ to ureteric distension was recorded.
      The bladder was then filled with 400 ml saline at two rates, slow (10 ml/min) and
      rapid (150 ml/min), and UVJ pressure response was registered. The aforementioned
      tests were repeated after anesthetizing the UVJ, the bladder musculature
      surrounding the UVJ and the ureteric wall at the site of the ureteric distension,
      respectively. Ureteric distension of the lower 2-3 cm effected ureteric pressure
      elevation (P < 0.05) and a UVJ pressure drop (P < 0.05); no pressure response of
      the UVJ occurred upon ureteric distension above this level. Slow bladder filling
      induced an increase in the UVJ (P < 0.01) and vesical (P < 0.01) pressures only
      when vesical filling reached a mean of 219.6 +/- 79.4 ml and above. Upon rapid
      vesical filling the pressure response occurred at a smaller volume (136.6 +/-
      52.3 ml). The pressure response did not occur when the UVJ was anesthetized. The
      study showed that lower ureteric distension was associated with a UVJ pressure
      drop. This reflex relationship, which we call the "ureterovesical junction
      inhibitory reflex," was reproducible and disappeared on anesthetizing the UVJ or
      ureter. Vesical filling above a certain volume induced a UVJ pressure increase
      which was reproducible and disappeared on anesthetizing the UVJ; we call this
      reflex relationship the "vesicoureteral junction excitatory reflex." These two
      reflexes seem to regulate the entry of urine from the ureters to the bladder and
      prevent ureteric reflux during bladder filling. In conclusion, two reflexes are
      identified that might contribute to the mechanism of UVJ antireflux.

PMID- 9008327
TI  - Ureaplasma urealyticum-induced urinary tract stones in rats.
AB  - This study investigated the possible role of Ureaplasma urealyticum, which is
      predominantly located in the urogenital tract, in the formation of infectious
      stones. A standardized Ureaplasma urealyticum broth culture isolated from a human
      urogenital specimen was inoculated into the renal medulla of five male rats
      (Rattus norvegicus L., Wistar C, weighing 170 +/- 10 g) and the same amount of
      culture media was used for five identical control rats. Five days after the
      inoculation, the rats were killed and fresh preparations from the bladders and
      the inoculated kidneys of both groups were prepared. At the same time biochemical
      and histopathological analysis of the contents of the bladders and the inoculated
      kidneys of both groups was performed. Crystal formation within the bladders of
      the inoculated rats was demonstrated and biochemical analysis of the crystals
      showed calcium, magnesium and phosphate, which indicated the existence of
      infection-induced crystals. These findings were absent in the control rats. The
      role of Ureaplasma in the production of urinary tract infectious stones was thus
      demonstrated in vivo.

PMID- 9008328
TI  - Expression of HGF mRNA in human rejecting kidney as evidenced by in situ
      hybridization.
AB  - In situ hybridization was performed to demonstrate hepatocyte growth factor (HGF)
      mRNA in two patients with normal kidney and in 23 patients with allograft
      nephrectomy. In situ hybridization was combined with immunohistochemistry to
      identify HGF-producing cells. In the two patients with normal kidney, no HGF mRNA
      was obtainable. In 15 of the 23 allograft patients, signals of HGF mRNA were
      detectable. In six of these 15 patients, the signals were present mainly at the
      medullocortex junction, and in the other nine patients at the cortex and/or
      medulla. Strong and frequent signals were present in gland-like structures in 15
      cases. Some scattered signals were also present in the fibrosed glomeruli in five
      cases, in the thickened intimas of large arteries in three cases, and in the
      arterial muscle coats of two cases. Combined immunohistochemistry and in situ
      hybridization showed that HGF mRNA-positive cells in gland-like arrangements were
      also positive for cytokeratin and negative for factor VIII. Cells with HGF mRNA
      signal and located in the arterial media were also positive for actin. These
      findings suggest that HGF mRNA is transcribed both in the urinary tubular
      epithelium and in the mesenchymal cells (fibroblasts, and smooth muscle cells in
      chronic vascular rejection and endothelial cells and/or mesangial cells in
      transplant glomerulopathy) in human rejecting kidney.

PMID- 9008329
TI  - Water-jet dissection in renal surgery: experimental study of a new device in the
      pig.
AB  - The pig model was used for experiments with a new type of water-jet dissector,
      which produces high-pressure water by application of a gas and maintains the
      water fully sterile in a single-use delivery apparatus. The experiment was
      conducted ex vivo (14 kidneys) and in vivo to compare electric cautery section
      with water-jet dissection (5 vs 11 partial nephrectomies). Ex vivo study
      confirmed sparing of blood vessels and pelvicaliceal system. In vivo study did
      not show significant differences in blood loss but, the water-jet allowed precise
      dissection and tight closure of the excretory system. More frequent haemorrhages
      were noted on histological examination of the WJ group, but no coagulation
      necrosis. These are preliminary findings and further studies of long-term results
      may confirm the benefits of the absence of parenchymal necrosis and the definite
      advantage of precise closure of the pelvicaliceal system, as morbidity of partial
      nephrectomy is often related to secondary haemorrhages and urinary fistulae.

PMID- 9008330
TI  - Changes in urinary output and electrolytes during gaseous and gasless
      laparoscopy.
AB  - Urological laparoscopy has gained increasing acceptance recently. Alterations in
      renal water and electrolyte homeostasis by carbon dioxide peritoneal
      insufflation, retroperitoneal insufflation and abdominal wall lifting were
      measured in 30 well-hydrated pigs over a 2-h period. Oliguria was observed after
      gaseous insufflation but not alter lifting the abdominal wall. Return to normal
      urinary output was observed at 30 min after release of pneumoretroperitoneum, and
      60 min after pneumoperitoneum. Creatinine clearance declined, while the clearance
      rates of potassium, sodium and urea remained unchanged during peritoneal and
      retroperitoneal insufflation. An elevated serum aldosterone concentration was
      found which may mediate the increased urinary excretion of potassium and
      decreased urinary excretion of sodium found during peritoneal insufflation. Renal
      function remained stable, despite an elevation of serum creatine kinase being
      elicited after lifting the abdominal wall. In conclusion, significant changes in
      water and electrolyte homeostasis occurred gaseous, not gasless, laparoscopy in
      pigs.

PMID- 9008331
TI  - Experimental autoimmune cystitis in the Lewis rat: a potential animal model for
      interstitial cystitis.
AB  - To develop an autoimmune animal model for interstitial cystitis (IC), we injected
      rats with Freund's adjuvant (CFA) containing bladder homogenate (experimentals)
      or CFA alone (shams). We observed a doubling of urinary frequency in the
      experimental animals over the shams (P = 0.004) and histopathologic changes
      (venular congestion) consistent with IC. Statistically significant bladder
      capacity changes were not found. Mast cell (MC) number was not statistically
      different between experimentals and controls but the number of MCs from section
      to adjacent section within the same animal's bladder did vary markedly,
      indicating the MC counts are not a reliable measure of disease in the rat
      bladder. Splenocytes cultured from the experimental animals and transferred to
      naive syngeneic recipients were capable of transferring the urinary frequency
      changes and vascular congestion while splenocytes from animals which did not
      develop the condition were without effect. In summary, we have developed and
      autoimmune model for IC consistent with the clinical features of IC. The features
      of this model can be transferred to naive syngeneic recipients via adoptive
      splenocyte transfer. The model will permit us to ask and answer important
      questions about the pathogenesis and treatment of the human disease.

PMID- 9008333
TI  - Sequence analysis of the putative viral enhancer in tissues from 33 cats with
      various feline leukemia virus-related diseases.
AB  - Diseases resulting from infection by feline leukemia virus (FeLV) and several
      other retroviruses relate in part, to non-coding regulatory sequences within the
      viral long terminal repeat (LTR). Both enhancer repeats and mutations within the
      LTR have been implicated in FeLV related disease. In order to investigate the
      relationship between nucleotide sequence of the FeLV LTR and disease, tissues
      from 33 cats with different types of degenerative and proliferative FeLV-related
      disease were studied. An FeLV LTR region containing the putative transcriptional
      enhancer unit was amplified by polymerase chain reaction (PCR) from FeLV-infected
      tissues. Phylogenetic analysis of FeLV 3'unique (U3) sequences revealed only one
      meaningful grouping which contained 4 of the 5 antigen-negative lymphosarcomas
      (LSAs). No sequence duplications were found in any of the 33 FeLV U3 regions.
      Point mutations relative to the corresponding region of FeLV-A/Glasgow, were
      identified at 102 positions; 68 of these were accounted for by mutations at 5
      locations. Only 1 point mutation was found within the leukemia virus b-simian
      virus 40-like core (LVb-CORE) site. However, the nuclear factor 1 (NF1) site
      contained 11 mutations, and the FeLV-specific (FLV-1) site contained 26
      mutations. Most of the remaining mutations were upstream of the LVB site between
      glucocorticoid response element (GRE) and FLV-1. The 10 LSAs, particularly the 5
      antigen-negative LSAs, deviated least from the corresponding sequence for FeLV
      A/Glasgow. Conclusions were that the spectrum of neoplastic and non-neoplastic
      FeLV-related diseases investigated in this study, developed in the presence of
      FeLVs containing the single enhancer unit. The significance of the point
      mutations is unknown, however, those occurring with high frequency and within
      nuclear protein binding should be first to be investigated in functional studies.

PMID- 9008332
TI  - Elevated concentrations of gamma-enolase in renal cell tumors in rats: similarity
      to renal cell carcinoma in man.
AB  - Concentrations of enolase isozymes in normal kidney and renal cell tumors in rats
      were determined using a highly sensitive enzyme immunoassay, and the isozymes
      were immunohistochemically localized in tissue sections. Levels of alpha-enolase
      in renal cell tumors were significantly lower than in normal kidney, whereas
      those of gamma-enolase were significantly elevated (mean +/- SD: 211 +/- 129
      ng/mg protein, n = 15, as compared to 27.1 +/- 2.9 ng/mg protein, n = 7). The
      proportion of gamma-enolase in the total enolases in the tumor tissues (1.6 +/-
      0.5%) was significantly higher than in normal kidney (0.15 +/- 0.05%).
      Immunohistochemistry revealed epithelial cells of all nephron segments to be
      positive for the alpha-isozyme, whereas gamma-enolase staining was strongly
      positive only in the loops of Henle, being faint in the distal tubules and absent
      in the proximal tubules. Both alpha- and gamma-enolases demonstrated positive
      immunostaining in all of the seven renal cell tumors studied. These findings
      indicate that an isozyme switch from alpha- to gamma-enolase occurs during rat
      kidney carcinogenesis, taking into account the derivation from proximal tubules,
      consistent with the findings for renal cell carcinomas in man.

PMID- 9008334
TI  - Detection of canine herpesvirus 1 in a wide range of tissues using the polymerase
      chain reaction.
AB  - Canine herpesvirus 1 (CHV-1), a member of the alphaherpesvirus sub-family, is
      known to cause fatal infections in litters of puppies and may also be involved in
      infertility, abortion, and stillbirths in adult dogs. The purpose of this study
      was to determine the presence of CHV-1 DNA using the polymerase chain reaction
      (PCR) in twelve key sites that have been associated with latency for the other
      herpesviruses. A 605 base pair portion of the viral glycoprotein B (gB) gene was
      amplified using degenerate primers, cloned, and sequenced. Conventional 20 mer
      primers were designed using this sequence information to amplify a 120 bp
      fragment of gB situated between the original degenerate primers. The specificity
      of amplification was confirmed by Southern Blot hybridisation using an internal
      oligonucleotide probe. DNA was extracted from tissue samples taken from twelve
      dogs at post mortem and from twenty-four blood samples. Nine out of twelve dogs
      showed evidence of infection with CHV-1; the tissues most commonly affected were
      lumbo-sacral ganglia (5/12 dogs), tonsil (5/12), parotid salivary gland (4/9),
      and liver (4/9). No positive results were detected within the twenty-four blood
      samples. These results indicate that exposure to CHV-1 may be much more common
      than previously suggested.

PMID- 9008335
TI  - Protectotypic differentiation of avian infectious bronchitis viruses using an in
      vitro challenge model.
AB  - Two vaccine and three virulent strains of infectious bronchitis virus (IBV) were
      used to infect day-old specific-pathogen-free chickens. Precocious development of
      oviducts was induced in young female chicks by oestrogen injections. Tracheal and
      oviduct organ cultures prepared from immunised chickens were challenged in vitro
      with homologous and heterologous viruses to assess tracheal and oviduct cross
      protection. Tracheal cross-protection was seen between serologically related and
      unrelated viruses. Protection at at the level of the oviducts was lower compared
      to that seen at the tracheal level. However, the yields of the homologous
      challenge viruses from immunised oviducts were significantly reduced as compared
      to yields from normal oviducts. After challenge, tracheal and oviduct ciliary
      scores were used to group the five strains of IBV into protectotypes. The five
      viruses could be grouped into three protectotypes and four serotypes. The
      virulent IBV strains were found to have caused complete stasis of oviduct cilia
      when examined at three weeks post-infection. Oestrogen treatment of chicks did
      not significantly alter the lymphocyte proliferation responses to concanavalin A
      or pokeweed mitogen. The applicability of this model for the study of protection
      afforded to the oviducts, in terms of protection against virus-induced damage,
      rather than drop in egg production, is discussed.

PMID- 9008336
TI  - Subgrouping of bovine respiratory syncytial virus strains detected in lung
      tissue.
AB  - Bovine respiratory syncytial virus is an important respiratory pathogen in
      cattle. Recently, subgroups of BRSV have been identified, based on antigenic
      differences. However, little is known about subgroups of BRSV that circulate in
      the cattle population. Therefore, we determined the reactivity of monoclonal
      antibodies (mAbs), directed against the G, F, or P protein of BRSV, with lung
      tissue from 47 calves, that suffered from severe respiratory disease. Fourteen
      animals (30%) proved to be infected with BRSV, because they all reacted with mAbs
      against the P or F protein, as detected by fluorescent antibody tests. Monoclonal
      antibodies against the G protein were able to discriminate between the BRSV
      positive specimens: 7 strains were identified as subgroup A strains, and 5
      strains as subgroup AB, which is introduced as BRSV subgroup in this paper. Two
      strains could not be identified unambiguously. It is concluded that BRSV subgroup
      A and AB were associated with severe respiratory disease, and that strains
      belonging to either subgroup circulated concurrently in the cattle population in
      the Netherlands.

PMID- 9008337
TI  - Characterization of enzootic nasal tumor virus capsid antigen.
AB  - The RT-PCR was carried out on tumor tissue from sheep with enzootic nasal tumor
      (ENT), using primers designed from conserved amino acid regions of related type D
      retroviruses. A 591 bp PCR fragment, corresponding to 90% of the capsid antigen
      was cloned, sequenced and expressed in E. coli. Alignment with ovine pulmonary
      carcinoma (OPC) virus showed 93% nucleotide and 96% amino acid homology. No
      amplification occurred when DNA from ovine fetal cell line was used as template.
      The recombinant protein, highly expressed in prokaryotic system, reacted in
      immunoblot with mouse antiserum to Mason Pfizer monkey virus (MPMV) p27, as well
      as sera from OPC and ENT diseased animals. Preliminary application of this
      antigen in ELISA suggested its potential use to detect seropositive animals in
      infected flocks.

PMID- 9008338
TI  - Negative regulation of immediate-early gene expression of pseudorabies virus by
      interferon-alpha.
AB  - Pseudorabies rabies (PrV) replication in Vero cells was suppressed by treatment
      with human natural interferon-alpha (IFN-alpha). Messenger RNA transcribed from
      the PrV immediate-early (IE) gene was reduced in the IFN-alpha-treated cells.
      Transient expression assays showed that transcription from the PrV IE promoter
      was selectively inhibited in the IFN-alpha-treated cells. Analysis of deletion
      mutants of the PrV IE promoter sequence suggested that at least one element
      between the transcription initiation site (+1) and -90 in the PrV IE promoter was
      concerned with the negative regulation.

PMID- 9008339
TI  - Differentiation of vaccine virus from field isolates of feline panleukopenia
      virus by polymerase chain reaction and restriction fragment length polymorphism
      analysis.
AB  - In an attempt to distinguish feline panleukopenia virus (FPLV) live vaccine
      strains from FPLV field isolates in Japan, we compared restriction fragment
      length polymorphisms (RFLP) of polymerase chain reaction (PCR)-amplified
      fragments of live FPLV vaccine strains with those of FPLV Japanese field
      isolates. On the basis of nucleotide sequence differences between PLI-IV, a live
      vaccine strain, and FPV-483, a recent field isolate, two restriction enzymes, Dra
      I and Afa I, were selected for PCR-RFLP analysis of nucleotide (nt) differences
      at nt 3695 and 4508, respectively. Three live vaccine strains including the PLI
      IV strain could be distinguished from the Japanese field isolates by their PCR
      RFLP patterns by Afa I, but one live vaccine strain was indistinguishable from
      the Japanese isolates when Dra I and Afa I were used. The Japanese field isolates
      were divided into two groups by the profile of PCR-RFLP patterns generated by Dra
      I and Afa I, suggesting that PCR-RFLP analysis using several enzymes provides a
      good genetic estimate of strain differentiation. No isolate that shows a Dra I
      negative/Afa I-negative pattern has emerged in Japan, indicating the possibility
      that the live vaccine viruses with a Dra I-negative/Afa I-negative pattern, such
      as the PLI-Iv strain, are candidates for use as live FPLV vaccine strain in Japan
      where they can be genetically distinguished from field strains.

PMID- 9008340
TI  - Macrophage inhibitory factor-A3 derived from Mycobacterium avium serovar 2
      inhibits candidacidal activity of murine peritoneal macrophages.
AB  - Macrophage inhibitory factor-A3 (MIF-A3), a fraction derived from Mycobacterium
      avium serovar 2 inhibited candidacidal activity in macrophages from C57BL/6,
      C57BL/10, C3H/HeJ and A/J strains of mice. Inhibition of candidacidal activity
      was demonstrated at MIF-A3 concentrations ranging from 100-400 micrograms/ml in
      macrophages without additional stimulators (exception C3H/HeJ macrophages) and in
      macrophages additionally stimulated with 200 U/ml interferon-gamma, 100 ng/ml
      phorbol myristate acetate and 0.4 ng/ml E. coli lipopolysaccharide from all mouse
      strains tested. The decreased candidacidal effect produced by MIF-A3 was dose
      dependent and appeared greatest in macrophages treated with phorbol myristate
      acetate and lipopolysaccharide. This effect was neutralized by the addition of
      goat anti-MIF-A3 antiserum. Macrophages from the Bcgs mouse strains (C57BL/6 and
      C57Bl/100 were more sensitive to the effect(s) of MIF-A3 than macrophages from
      the Bcgr mouse strains (C3H/HeJ and A/J).

PMID- 9008341
TI  - Characterization of an outer membrane protein of Pasteurella multocida belonging
      to the OmpA family.
AB  - The outer membrane vesicle and N-lauroylsarcosine-insoluble protein preparations
      of Pasteurella multocida 656 were analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. A major outer membrane protein (OMP) was
      found to be heat-modifiable, having a molecular mass of 28 kDa when the OMP
      preparation was solubilized at 60 degrees C and a molecular mass of 37 kDa when
      it was solubilized at 100 degrees C. A monoclonal antibody, designated mAb MT4.1,
      was generated against heat-modifiable OMP of P. multocida. This mAb reacted with
      the heat-modifiable OMP irrespective of the temperature at which it was
      solubilized, as demonstrated by immunoblot results. The heat-modifiable OMP of P.
      multocida showed a significant N-terminal amino acid sequence homology with OmpA
      family. Immunoelectron microscopic study revealed that the mAb Mt4.1 epitope was
      not surface exposed on the intact bacterium. The mAb MT4.1 reacted with all the
      reference strains of 5 capsular and 16 somatic serotypes, as well as with 75
      field strains of P. multocida in immunoblot assay. This mAb MT4.1 also reacted
      with strains of various other Pasteurella species such as P. stomatis, P.
      aerogenes P. gallinarum, P. betti, P. sp, B, P. SP-g and P. canis, but not with
      strains of 12 other Gram-negative bacteria. These results indicated that this
      protein carried a genus-specific epitope and mAb MT4.1 may be useful for
      identification of Pasteurella species. This is the first report in which a major
      heat-modifiable OMP has been identified and characterized using a mAb, and has
      been shown belonging to the OmpA family.

PMID- 9008342
TI  - Genotypic and phenotypic diversity of Streptococcus dysgalactiae strains isolated
      from clinical and subclinical cases of bovine mastitis.
AB  - This study was conducted to characterize Streptococcus dysgalactiae isolated from
      cases of bovine mastitis. One hundred strains from 100 dairy herds in Denmark, 29
      strains from 29 dairy herds in Pennsylvania, USA, 7 reference strains and 18
      strains consisting of 9 paired strains from 9 quarters were investigated using
      biotyping (utilization of tagatose and sorbitol) and HindIII ribotyping. Four
      different biotypes were observed. Only 34 of the 100 Danish strains utilized
      either tagatose or sorbitol, 18 utilized tagatose, 15 sorbitol and 1 both
      tagatose and sorbitol. In contrast, among the American strains one (3.4%) did
      neither utilize tagatose or sorbitol, twenty (69.0%) utilized tagatose, four
      (13.8%) sorbitol and four (13.8%) both tagatose and sorbitol. HindIII ribotyping
      produced 15 different types among all the strains, 9 different types were found
      among the Danish strains and 8 types among American strains. Five types were
      observed among both the Danish and the American strains. The 7 reference strains
      were assigned to 5 different ribotypes. Three type strains (ATCC 27957, NCTC
      4670, NCTC 4335) were assigned to a type that was present among both the Danish
      and the American strains. Ribotyping was the most discriminatory typing method.
      Agreement between ribo- and biotyping was observed, and especially pronounced
      among the Danish strains. The 9 paired strains were in case found to have
      identical ribo- and biotype.

PMID- 9008343
TI  - Competitive enzyme-linked immunosorbent assay using monoclonal antibodies to the
      Brucella melitensis BP26 protein to evaluate antibody responses in infected and
      B. melitensis Rev.1 vaccinated sheep.
AB  - Competitive enzyme-linked immunosorbent assay (C-ELISA) was performed using 15
      monoclonal antibodies (MAbs), specific for Brucella BP26 (previously also called
      CP28), a periplasmic protein antigen, to investigate antibody responses in
      naturally and B. melitensis H38 experimentally infected and B. melitensis Rev.1
      vaccinated sheep. The antigen preparation consisted of cytosoluble protein
      extract (CPE) of B. melitensis B115. By combining the C-ELISA results of several
      MAbs, a high percentage of naturally infected animals were detected which showed
      different status in the current conventional diagnostic tests. Indeed, 90% of
      sheep which were positive in the conventional bacteriological and serological
      tests were positive in C-ELISA. 72% of the bacteriologically negative but
      serologically and delayed type hypersensitivity positive sheep were also positive
      in the C-ELISA. Moreover, 79% of the bacteriologically and serologically negative
      sheep but delayed type hypersensitivity positive were also detected by C-ELISA.
      Thus, these results confirmed the importance of BP26 as a frequently recognized
      target of the humoral immune response of infected sheep. The 8 B. melitensis H38
      experimentally infected sheep showed various degrees of antibody responses at the
      90th day after infection, which was delayed in comparison to that against O
      polysaccharide (O-PS). Of the 15 MAbs tested, only one MAb was weakly inhibited
      (20 to 35% inhibition) by 56% of negative control sera. Furthermore, no antibody
      response against BP26 was detected in B. melitensis Rev.1 vaccinated sheep.
      Results of the C-ELISA with the 15 MAbs showed individual variability of the
      antibody responses against BP26. Thus, it is suggested that several epitopes of
      BP26 are of interest for diagnosis of B. melitensis infection in sheep.

PMID- 9008344
TI  - Secreted antigens as virulence associated markers in Streptococcus bovis strains
      from pigeons.
AB  - SDS-PAGE and Western blot analysis were performed on the culture supernatant of 7
      pigeon S. bovis reference strains belonging to the serotypes 1, 2, 3 and 5. The
      culture supernatant of highly virulent serotype 1, 2 and 5 strains contained four
      antigens that were absent in low virulent serotype 3 strains, notably a 185 kDa
      minor protein band (A) and a triplet (T1) of 70 kDa. The less virulent serotype 3
      strains on the other hand contained protein triplets, that had a molecular mass
      of either 68 kDa (T2) or 74 kDa (T3). The prevalence of A, T1, T2 and T3 was
      examined in 68 S. bovis strains isolated from healthy pigeons and in 68 S. bovis
      strains isolated from pigeons that died of S. bovis septicaemia. Six supernatant
      phenotypes were identified: A-T1 (32 strains), A- T2 (10 strains), A- T3 (7
      strains), A+ T1 (84 strains), A+ T2 (1 strain) and A+ T3 (2 strains). Ninety-four
      percent of the strains lacking the A and T1 proteins were isolated from healthy
      pigeons, and only 6% were isolated from septicaemia. Strains expressing A and/or
      T1, however, were isolated form septicaemia in 57% of the cases. These
      observations may indicate that the A and/or T1 proteins are associated with
      virulence.

PMID- 9008345
TI  - Serogroups, toxins and antibiotic resistance of Escherichia coli strains isolated
      form diarrhoeic goat kids in Spain.
AB  - Fifty-five Escherichia coli strains isolated from 55 diarrhoeic goat kids from 13
      flocks in Spain were serotyped and investigated for production of enterotoxins
      (LT and STa), verotoxins (VT1 and VT2), cytotoxic necrotizing factors (CNF1 and
      CNF2), alpha-hemolysin (Hly) and enterohemolysin (EntHly), and for antibiotic
      resistance. Only 3 (5%) strains were toxigenic: 1 VT1+EntHly+ (serogroup O8) and
      2 CNF2+ (both of serogroup O153). The strains serotyped belonged to 19
      serogroups. However, 31 (56%) were of one nine serogroups (O3, O8, O9, O10, O11,
      O21, O44, O103 and O153) and only three of them (O8, O9 and O11) accounted for
      29% of the strains. The highest percentages of antibiotic resistance in order of
      frequency were: streptomycin (93%), sulfadiazine (89%), tetracyline (84%),
      kanamycin (82%), neomycin (82%) and ampicillin (69%). We conclude that E. coli
      strains isolated from diarrhoeic goat kids are usually non-toxigenic and belong
      to a large number of serogroups.

PMID- 9008346
TI  - Virulence of feline Chlamydia psittaci in mice is not a function of the major
      outer membrane protein (MOMP).
AB  - The virulent strain of feline Chlamydia psittaci, the Cello strain, produces
      conjunctivitis and upper respiratory disease in cats. This same strain produces a
      lethal disease in mice when inoculated intraperitoneally (i.p.). In this study we
      have shown that the Baker strain of feline C. psittaci is attenuated in the mouse
      model system. Intraperitoneal inoculation of mice with the Baker strain produced
      no disease but did stimulate an immune response that protected the mice from
      subsequent produced i.p. inoculation with the virulent Cello strain. To determine
      if the difference between these two strains was in the major outer membrane
      protein (MOMP), the omp1 gene which codes for this protein was sequenced for both
      the Baker and Cello strains. The MOMP was chosen to study because in Chlamydia
      trachomatis this protein has been shown to contain neutralizing epitopes and has
      been shown to play a role in cell attachment. These functions make it a likely
      structural component capable of mutating and causing altered cell tropism and
      virulence. The DNA sequence of the omp1 was determined by amplifying the gene
      with PCR, cloning the PCR product into the pCR-II cloning vector and determining
      the DNA sequence of the inserted gene using primers to sites in the plasmid
      vector. From the DNA sequence, the deduced amino acid sequence of MOMP was
      determined for both the attenuated Baker and the virulent Cello strains of feline
      C. Psittaci. The results indicated that the omp1 gene of both strains contained
      1179 base pairs which coded for a protein 392 amino acids. The DNA sequences of
      the omp1 gene of the two strains differed by only two base pairs which resulted
      in two amino acid changes in the MOMP. The Baker strain had a serine instead of a
      tryptophan at amino acid 7 and a tyrosine instead of an aspartic acid at amino
      acid 125 of the uncleaved protein. Neither amino acid change was in an area of
      the MOMP which could logically account for the difference in biological activity.
      Amino acid 7 was in the leader sequence which is cleaved from the authentic MOMP
      and is not present in the infectious elementary body. Amino acid 125 was in a
      conserved hydrophobic area of one of the constant regions of the protein. A
      change at this location was not likely surface exposed and thus could not affect
      cell adhesion, tissue tropism or neutralizing epitopes. Therefore, the
      differences in the primary structure of the MOMP from the Baker and Cello strains
      of feline C. psittaci could not account for the attenuation of the Baker strain
      for mice. The molecular basis of their difference is yet to be determined.

PMID- 9008347
TI  - Virulence attributes of Escherichia coli isolated from dairy heifer feces.
AB  - Escherichia coli isolates from 1,305 (of 6,894) fecal samples collected during
      the 1991-1992 USDA, Animal and Plant Health Inspection Service, National Health
      Monitoring System, Diary Heifer Evaluation Project were tested for virulence
      attributes associated with human enterohaemorrhagic E. coli (EHEC) and the
      enterotoxin commonly associated with diarrhoea in newborn calves. Single, random
      isolates from each heifer were hybridized to probes derived from the 60 mDa EHEC
      plasmid (CVD 419), E. coli attaching and effacing gene (eae), Shiga-like toxin
      (slt) genes I and II, and E. coli heat-stable enterotoxin a (STaP). Seventy-seven
      of the 1305 isolates (5.9%) were slt-positive. Most (81.8%) slt-positive E. coli
      were also CVD 419 and eae-positive. Only 2 of the slt-positive E. coli isolates
      were STaP-positive.

PMID- 9008348
TI  - Population networks: a large-scale framework for modelling cortical neural
      networks.
AB  - Artificial neural networks are usually built on rather few elements such as
      activation functions, learning rules, and the network topology. When modelling
      the more complex properties of realistic networks, however, a number of higher
      level structural principles become important. In this paper we present a
      theoretical framework for modelling cortical networks at a high level of
      abstraction. Based on the notion of a population of neurons, this framework can
      accommodate the common features of cortical architecture, such as lamination,
      multiple areas and topographic maps, input segregation, and local variations of
      the frequency of different cell types (e.g., cytochrome oxidase blobs). The
      framework is meant primarily for the simulation of activation dynamics; it can
      also be used to model the neural environment of single cells in a multiscale
      approach.

PMID- 9008349
TI  - Competition in the temporal domain among neural activities phase-locked to
      subthreshold oscillations.
AB  - In the presence of a subthreshold membrane oscillation, analog information may be
      encoded in the timing of spike generation phase-locked to the oscillation. With
      this spike timing neural code, a competitive network of inhibitory spiking
      neurons was shown to achieve a novel timing mechanism of neural activity
      selection: the neurons had higher probabilities of becoming winners if they were
      stimulated earlier in each oscillatory cycle. Here the timing mechanism and its
      robustness are studied both numerically and analytically, and the conditions to
      yield a given number of winners (the inhibitory neurons that remain active after
      the competition) are investigated. The analysis revealed that activity selection
      with a small number of winners is ensured for broad ranges of values of the
      parameters such as the strength and time constant of inhibition. In particular,
      the number of winners is almost unchanged for various timing differences between
      stimuli to different neurons. This implies that the timing mechanism is useful
      for such biological information processing as required perception of a relatively
      small number of significant stimulus components.

PMID- 9008350
TI  - A mathematical model of activity-dependent, anatomical segregation induced by
      competition for neurotrophic support.
AB  - Mathematical or computational models of activity-dependent neural competition
      typically impose competition in anatomically fixed networks by the use of
      synaptic normalisation, for which there is very little experimental support.
      Recent experimental evidence, however, strongly implicates neurotrophic factors
      in neural plasticity and competition, in addition to their well-known potent
      effects on neurite outgrowth and synaptogenesis. We therefore present a simple,
      mathematical model of anatomical segregation induces by activity-dependent
      competition for a limited supply of a neurotrophic factor provided by target
      cells to afferents. We extract the behaviour of the model in various regimes, in
      which the neurotrophic factor is either in critical supply or in abundant supply,
      by a combination of analytical and numerical methods, and study the effects of
      correlations in afferent inputs on competition. We apply the model to three
      different systems: ocular dominance column formation; elimination of polyneuronal
      innervation at the vertebrate neuromuscular junction; trigeminal brain stem
      whisker-related structure formation. Several classes of related predictions
      emerge, including the prediction that kittens reared with strabismus should
      require a higher concentration of neurotrophic factor infusion into their primary
      visual cortex than normally reared cats in order to induce the anatomical
      desegregation of ocular dominance columns. We also speculate on the mechanisms of
      support of inhibitory rather than excitatory neurons, and suggest the existence
      of a separate, (Cl-)-mediated activity-dependent pathway for their neurotrophic
      support.

PMID- 9008352
TI  - A neural network simulation of the vestibular system: implications on the role of
      intervestibular nuclear coupling during vestibular compensation.
AB  - Previous neural network simulations of the vestibular system have been based
      loosely on known physiology. This research involved the use of a strongly
      physiologically based neural network model which was used to investigate the role
      of the vestibular commissure in restoring the bilateral symmetry of the resting
      rates of the vestibular nuclei during vestibular compensation following
      unilateral labyrinthectomy. It was found the readjustments in the gain of the
      vestibular commissure were not primarily responsible for vestibular compensation,
      as has previously been suggested, but rather that it was modifications in
      extralabyrinthine sources of tone which mediated the restoration of the central
      symmetry between the two nuclei.

PMID- 9008351
TI  - Electrical activity of the sensory afferent pathway in the enteric nervous
      system.
AB  - In this paper we develop a mathematical model for the electrical activity of the
      afferent pathway, formed from the coupled primary and secondary sensory neurons.
      The primary sensory neuron possesses the electrical properties of AH neurons and
      morphological characteristics of Dogiel type II neurons; the secondary sensory
      neuron displays the tonic type of electrical behavior and has morphological
      features of Dogiel type III neurons. Free nerve endings of the mechanoreceptor
      form the receptive field of the pathway. Based on the general principles of the
      Hodgkin-Huxley description of excitable cells, the model simulates the following
      sequence of events: stretch of the receptive field initiates the dendritic
      potential at the mechanoreceptors; the excitation causes soma action potential
      development at the primary sensory neuron which is followed by soma action
      potential generation at the secondary sensory neuron. Numerical calculation have
      shown that the model is capable of reproducing different electrical patterns
      within the pathway under normal physiological conditions and after treatment with
      charybdotoxin, iberiotoxin, tetrodotoxin, omega-conotoxin GVIA, A1-A2
      purinoceptor agonists, a protein kinase C activator, and a delta-opioid receptor
      agonist. Comparison of the computational results with the results of experiments
      conducted on the neurons of the submucous and myenteric plexi of the small bowel
      demonstrates their good qualitative and quantitative agreement.

PMID- 9008353
TI  - Numerical bifurcation analysis of distance-dependent on-center off-surround
      shunting neural networks.
AB  - On-center off-surround shunting neural networks are often applied as models for
      content-address-able memory (CAM), the equilibria being the stored memories. One
      important demand of biological plausible CAMs is that they function under a broad
      range of parameters, since several parameters vary due to postnatal maturation or
      learning. Ellias, Cohen and Grossberg have put much effort into showing the
      stability properties of several configurations of on-center off-surround shunting
      neural networks. In this article we present numerical bifurcation analysis of
      distance-dependent on-center off-surround shunting neural networks with fixed
      external input. We varied four parameters that may be subject to postnatal
      maturation: the range of both excitatory and inhibitory connections and the
      strength of both inhibitory and excitatory connections. These analyses show that
      fold bifurcations occur in the equilibrium behavior of the network by variation
      of all four parameters. The most important result is that the number of
      activation peaks in the equilibrium behavior varies from one to many if the range
      of inhibitory connections is decreased. Moreover, under a broad range of the
      parameters the stability of the network is maintained. The examined network is
      implemented in an ART network, Exact ART, where it functions as the
      classification layer F2. The stability of the ART network with the F2-field in
      different dynamic regimes is maintained and the behavior is functional in Exact
      ART. Through a bifurcation the learning behavior of Exact ART may even change
      from forming local representations to forming distributed representations.

PMID- 9008355
TI  - Calcium and phosphorous deficiencies alter the lipid composition and fluidity of
      intestinal basolateral membranes.
AB  - Steady-state fluorescence polarization and lipid composition studies were
      undertaken on intestinal basolateral membranes (BLM) from chicks adapted to a
      calcium deficient (low Ca) or a phosphorous deficient diet (low P). The
      fluorescence anisotropy showed that fluidity of intestinal BLM was increased by
      the mineral deprivations, but the response of the membranes varied with the
      specific fluorophore used. The "static" component of fluidity, assessed by 1,6
      diphenyl-1,3,5-hexatriene (DPH), was increased whereas the "dynamic" component,
      monitored with DL-12-(9-anthroyloxy)-stearic acid (12-AS), was not modified. Low
      P diet produced significant changes in lipid composition such as a decrease in
      the cholesterol content and in the sphyngomyelin (Sph) and phosphatidylserine
      plus phosphatidylinositol fractions (PS + PI) and increment in the
      phosphatidylcholine (PC) proportion. The percent of monounsaturated fatty acids
      was increased by the low P diet due mainly to an increase in the oleic acid
      fraction. Minor changes such as a decrease in the palmitic acid and increases in
      the 22:5n3 and 22:6n3 fatty acids were caused by Ca deficiency. The alteration of
      the biochemical and biophysical membrane properties of the BLM of the mineral
      deficient groups might play a role in the enhanced intestinal Ca and P
      absorption.

PMID- 9008354
TI  - Lactation and pregnancy effects on blood flow to mammary and reproductive systems
      in heat-stressed rabbits.
AB  - This study used radioactive microspheres to examine blood flow distribution in
      the mammary and reproductive systems of hyperthermic (+1 degrees C), anesthetized
      laboratory rabbits at different stages of pregnancy and lactation. Ovarian,
      cervical and oviductal blood flows decreased by 20-30% during heat stress while
      vulval blood flow rose by 40%, irrespective of pregnancy and/or lactation status.
      Mammary blood flow was unaltered during heat stress at most pregnancy and/or
      lactation stages, with the exception of a 35% decrease in non-pregnant rabbits in
      early lactation. Uterine blood flow in non-pregnant rabbits in early and peak
      lactation decreased by 42% and rose by 33%, respectively. Uterine blood flow
      response to heat stress in pregnant animals varied among tissues: no changes
      occurred in the flow to implantation sites (early pregnancy) or to inter
      embryonic segments (mid- to late pregnancy); that to gestation sacs decreased by
      12-40% at the different lactation stages; and that to maternal placentas
      decreased in the lactating state by 18%, and rose in the non-lactating state by
      50%. Results indicate that pregnancy and lactation modulate vasomotor responses
      to heat stress in mammary and reproductive tissues, and that the extent of the
      modulation depends upon their respective stages.

PMID- 9008356
TI  - Urinary clearance of angiotensin II in Pekin ducks.
AB  - To quantify the renal excretion of angiotensin II (AII) in birds, synthetic AII
      was intravenously infused into conscious Pekin ducks at rates of 5, 15 and 45
      ng/kg/min for 30 min and the relationships between plasma and urine AII
      concentrations were monitored by radioimmunoassay. The infusions of AII produced
      dose-dependent elevations in the plasma concentrations of the hormone, however,
      urinary concentrations and excretion rates did not change significantly from the
      basal values of 11.6 +/- 1.2 pg/ml and 4.3 +/- 1.0 pg/min, respectively. The
      metabolic clearance rate of AII remained constant at each infusion dose
      (approximately 120 ml/min/kg). The urinary clearance rates (< 0.3 ml/min/kg)
      indicated that the fraction of AII cleared from the blood via the urine was less
      than 0.2%. Clearly, excretion of intact AII via this route is not a
      quantitatively important means of elimination for this hormone in birds.

PMID- 9008358
TI  - Bibliography of Comparative Biochemistry and Physiology A generated from the
      Current Awareness in Biological Sciences database.

PMID- 9008357
TI  - An estimate of the participation of the sarcoplasmic reticulum in the
      intracellular Ca2+ regulation in adult and newborn ferret hearts.
AB  - The aim of the present study was to estimate the participation of the
      sarcoplasmic reticulum in the Ca2+ regulation of the contraction of newborn
      ferret heart. Cyclopiazonic acid has been used to block the sarcoplasmic
      reticulum Ca2+ pump in adult and newborn (1 month and 5-6 day old) ferret
      ventricles of intact and saponin-treated preparations. Cyclopiazonic acid induced
      a decrease of the amplitude of the caffeine contractures generated in saponin
      skinned fibers. The sensitivity of the sarcoplasmic reticulum Ca2+ uptake to
      cyclopiazonic acid was similar in adult and newborn hearts. In intact
      preparations, cyclopiazonic acid (1-20 microM) induced a negative inotropic
      effect on the twitch with a prolongation in its kinetics. The maximal decrease in
      the amplitude of the twitch was larger in adult (92.4%) than in 1 month old
      (86.5%) and 5-6 day newborns (72.5%). Contrary to other species, where the
      sarcoplasmic reticulum Ca2+ pump is not functional in neonatal heart, it is
      proposed that ferret myocardium shows an early maturation of sarcoplasmic
      reticulum function.

PMID- 9008359
TI  - Solution structure of human neuropeptide Y.
AB  - The three-dimensional structure of synthetic human neuropeptide Y in aqueous
      solution at pH 3.2 and 37 degrees C was determined from two-dimensional 1H NMR
      data recorded at 600 MHz. A restraint set consisting of 440 interproton distance
      restraints inferred from NOEs and 11 backbone and 4 side-chain dihedral angle
      restraints derived from spin-spin coupling constants was used as input for
      distance geometry calculations on DIANA and simulated annealing and restrained
      energy minimization in X-PLOR. The final set of 26 structures is well defined in
      the region of residues 11-36, with a mean pairwise rmsd of 0.51 A for the
      backbone heavy atoms (N, C alpha and C) and 1.34 A for all heavy atoms. Residues
      13-36 form an amphipathic alpha-helix. The N-terminal 10 residues are poorly
      defined relative to the helical region, although some elements of local structure
      are apparent. At least one of the three prolines in the N-terminal region co
      exists in both cis and trans conformations. An additional set of 24 distances was
      interpreted as intermolecular distances within a dimer. A combination of distance
      geometry and restrained simulated annealing yielded a model of the dimer having
      antiparallel packing of two helical units, whose hydrophobic faces form a well
      defined core. Sedimentation equilibrium experiments confirm the observation that
      neuropeptide Y associates to form dimers and higher aggregates under the
      conditions of the NMR experiments. Our results therefore support the structural
      features reported for porcine neuropeptide Y [Cowley, D.J. et al. (1992) Eur. J.
      Biochem., 205, 1099-1106] rather than the 'aPP' fold described previously for
      human neuropeptide Y [Darbon, H. et al. (1992) Eur. J. Biochem., 209, 765-771].

PMID- 9008360
TI  - Elucidation of the origin of multiple conformations of the human alpha 3-chain
      type VI collagen C-terminal Kunitz domain: the reorientation of the Trp21 ring.
AB  - The human alpha 3-chain type VI collagen C-terminal Kunitz domain fragment (alpha
      3(VI)) has been studied by two dimensional 1H-1H and 1H-13C NMR spectroscopy at
      303 K. It is shown that the secondary structure of the protein is strikingly
      similar to that of BPTI, and a number of unusual H alpha chemical shifts, which
      are highly conserved in Kunitz-domain proteins, are also observed for a alpha
      3(VI). Furthermore, a series of exchange cross peaks observed in 1H-1H spectra
      shows that a large number of protons in the central beta-sheet exist in two
      different chemical environments, corresponding to two unequally populated
      conformations that are slowly exchanging on the NMR time scale. Several protons,
      including Ser47(53) H alpha, Arg32(28) H(gamma 1) and H(gamma 2), and GLN48(54)
      H(beta 2), all located in the vicinity of the Trp21(27) ring in the crystal
      structure of alpha 3(VI) [Arnoux, B. et al. (1995) J. Mol. Biol., 246, 609-617],
      have very different chemical shifts in the two conformations, the most affected
      being Gln48(54) H(beta 2) (delta sigma = 3 ppm), which is placed directly above
      the Trp21(27) ring in the crystal structure of alpha 3(VI). It should be
      concluded that the origin of the multiple conformations of the central beta-sheet
      is a reorientation of the Trp21(27) ring. From the intensities of corresponding
      signals in the two conformations, the populations, the population of the minor
      conformation was found to be 6.4 +/- 0.2% of that of the major conformation,
      while a rate constant kM = 1.01 +/- 0.05 s-1 for the major to minor
      interconversion was obtained from a series of NOESY spectra with different mixing
      times. In addition, it is shown that Cys14(20)-Cys38(44) disulfide bond
      isomerization, previously observed in BPTI [Otting, G. et al. (1993)
      Biochemistry, 32, 3571-3582], is also likely to occur in alpha 3(VI).

PMID- 9008361
TI  - Sequential assignment of 1H, 13C and 15N resonances of human carbonic anhydrase I
      by triple-resonance NMR techniques and extensive amino acid-specific 15N
      labeling.
AB  - The backbone NMR resonances of human carbonic anhydrase I (HCA I) have been
      assigned. This protein is one of the largest monomeric proteins assigned so far.
      The assignment was enabled by a combination of 3D triple-resonance experiments
      and extensive use of amino acid-specific 15N-labeling. The obtained resonance
      assignment has been used to evaluate the secondary structure elements present in
      solution. The solution structure appears to be very similar to the crystal
      structure, although some differences can be observed. Proton-deuteron exchange
      experiments have shown that the assignments provide probes that can be used in
      future studies of HCA I.

PMID- 9008362
TI  - 1H, 15N and 13C resonance assignments and secondary structure determination of
      the RNA-binding domain of E.coli rho protein.
AB  - Protein fragments containing the RNA-binding domain of Escherichia coli rho
      protein have been over-expressed in E. coli. NMR spectra of the fragment
      containing residues 1-116 of rho protein (Rho116) show that a region of this
      protein is unfolded in solution. Addition of (dC)10 to this fragment stabilizes
      the folded form of the protein. The fragment comprising residues 1-130 of rho
      protein (Rho130) is found to be stably folded, both in absence and presence of
      nucleic acid. NMR studies of the complex of Rho130 with RNA and DNA
      oligonucleotides indicate that the binding-site size, affinity, and specificity
      of Rho130 are similar to those of intact rho protein; therefore, Rho130 is a
      suitable model of the RNA-binding domain of Rho protein. NMR line widths as well
      as titration experiments of Rho130 complexed with oligonucleotides of various
      lengths suggests that Rho130 forms oligomers in the presence of longer
      oligonucleotides. 1H, 15N and 13C resonance assignments were facilitated by the
      utilization of two pulse sequences, CN-NOESY and CCH-TOCSY. The secondary
      structure of unliganded Rho130 has been determined by NMR techniques, and it is
      clear that the RNA-binding domain of rho is more structurally similar to the cold
      shock domain than to the RNA recognition motif.

PMID- 9008363
TI  - AQUA and PROCHECK-NMR: programs for checking the quality of protein structures
      solved by NMR.
AB  - The AQUA and PROCHECK-NMR programs provide a means of validating the geometry and
      restraint violations of an ensemble of protein structures solved by solution NMR.
      The outputs include a detailed breakdown of the restraint violations, a number of
      plots in PostScript format and summary statistics. These various analyses
      indicate both the degree of agreement of the model structures with the
      experimental dat, and the quality of their geometrical properties. They are
      intended to be of use both to support ongoing NMR structure determination and in
      the validation of the final results.

PMID- 9008364
TI  - A study of protein-water exchange through the off-resonance ROESY experiment:
      application to the DNA-binding domain of AlcR.
AB  - In this communication a new NMR experiment for the safe observation and
      quantification of water-protein exchange phenomena is presented. It combines a
      water-selective pulse, offering chemical shift-based separation, and the off
      resonance ROESY dynamic filter, which permits the elimination of the unwanted
      intramolecular dipolar cross relaxation of protein protons. Moreover, pulsed
      field gradients are used for the suppression of radiation damping and the solvent
      signal. The straightforward incorporation of this sequence in heteronuclear
      experiments is demonstrated for the case of the DNA-binding domain of the alcohol
      regulator protein.

PMID- 9008365
TI  - Dopaminergic modulation of visual responses in toads. I. Apomorphine-induced
      effects on visually directed appetitive and consummatory prey-catching behavior.
AB  - This study confirms for a phylogenetically basal terrestrial vertebrate that
      dopaminergic modulations interfere with the visually directed appetitive and
      consummatory feeding behaviors orienting and snapping, respectively. (1) In
      common toads Bufo bufo, intralymphatic administration of the dopamine D2/D1
      receptor agonist apomorphine led to a dose-dependent facilitation of prey
      snapping in response to moving objects. The snapping activity reached a maximum
      15-35 min after apomorphine injection. (2) To changes in configurational stimulus
      features, the basic pattern of discrimination was maintained; however, the acuity
      of discrimination was reduced due to the high snapping response level. (3) The
      apomorphine-induced facilitation of snapping was accompanied by a suppression of
      prey-oriented lunging and turning. Toads snapped only if prey occurred frontally
      in the visual field at a relatively short distance. The snapping behavior was
      fixed in its form and stereotyped regarding its immediate release. (4) About 90
      min after apomorphine administration, prey-oriented turning behavior was restored
      and displayed a facilitatory rebound. (5) In comparative experiments with the
      species B. marinus, both prey-oriented turning and snapping responses were
      suppressed by apomorphine in a dose-dependent manner. (6) After pre-treatment
      with the dopamine antagonist haloperidol, apomorphine showed no measurable effect
      on the visual release of prey orienting or snapping. (7) The results contribute
      to the sensorimotor and the motivation hypothesis of dopamine function proposed
      for higher vertebrates and stimulate a comparative discussion of anatomic
      homologies and functional analogies.

PMID- 9008366
TI  - Dopaminergic modulation of visual responses in toads. II. Influences of
      apomorphine on retinal ganglion cells and tectal cells.
AB  - The behavioral studies of Part I have shown in common toads that after systemic
      administration of the dopamine agonist apomorphine the prey-directed orienting
      turning movements are suppressed while prey snapping is facilitated. Part II
      focuses on retinal and tectal single cell responses to moving objects. (1) After
      systemic administration of apomorphine, the discharge rates of retinal class R2
      and R3 ganglion cell fibres--recorded from the retino-tectal projection--speeded
      up in response to visual objects traversing their excitatory receptive fields.
      This enhancing effect was independent of the recording site in the retino-tectal
      map. (2) The diameters of the excitatory receptive fields of R2 and R3 neurons
      doubled their sizes. Probably, apomorphine enhances the center-dominated
      excitatory responses at the expense of the strength of the inhibitory surround.
      (3) The apomorphine-induced effects were fully developed 20-35 min after drug
      administration. (4) At the same time the discharge rates of T5.1 and T5.2 tectal
      neurons were reduced under apomorphine. The effect was independent of the
      recording site in the retino-tectal map. The diameters of the excitatory
      receptive fields of these tectal neurons were not influenced. (5) To changes in
      configurational stimulus features, the basic pattern of discrimination was
      maintained. (6) It is suggested that tectal output to the turn-generating motor
      network--mediated by T5.1 and T5.2 neurons--is modulated by a pretecto-tectal
      pathway which involves dopaminergic pretectal cells. (7) The enhanced snapping
      can be interpreted in terms of a modulation of reticular/hypoglossal structures
      by dopaminergic preoptic/hypothalamic/solitary systems.

PMID- 9008370
TI  - Analysis of an SEIRS epidemic model with two delays.
AB  - A disease transmission model of SEIRS type with exponential demographic structure
      is formulated. All newborns are assumed susceptible, there is a natural death
      rate constant, and an excess death rate constant for infective individuals.
      Latent and immune periods are assumed to be constants, and the force of infection
      is assumed to be of the standard form, namely proportional to I(t)/N(t) where
      N(t) is the total (variable) population size and I(t) is the size of the
      infective population. The model consists of a set of integro-differential
      equations. Stability of the disease free proportion equilibrium, and existence,
      uniqueness, and stability of an endemic proportion equilibrium, are investigated.
      The stability results are stated in terms of a key threshold parameter. More
      detailed analyses are given for two cases, the SEIS model (with no immune
      period), and the SIRS model (with no latent period). Several threshold parameters
      quantify the two ways that the disease can be controlled, by forcing the number
      or the proportion of infectives to zero.

PMID- 9008367
TI  - The visual acuity of the frog (Rana pipiens).
AB  - The frog's visual acuity for gratings was tested with a two-choice prey-dummy
      setup. The two dummies had a constant position in the visual field, but in one of
      them a striped pattern was constantly drifting, while the other was a potentially
      less attention arousing dummy with non-moving stripes. The acuity was tested in
      bright white light and with different brightness levels of green light (500 nm).
      The highest acuity 2.8 cycles per degree was achieved with the maximum level of
      green light. When the brightness was lowered by six orders of magnitude the
      acuity fell to 0.7 cycles per degree. These behavioural acuities are compared
      with a theoretically calculated resolving power of the retinal ganglion cell
      array.

PMID- 9008371
TI  - When expectancy meets desire: motivational effects in reconstructive memory.
AB  - Two studies investigated the effects of motivational factors on expectancy use in
      reconstructive memory. Participants were given target's midterm grades for later
      recall; expectancies about the target's future performance were then manipulated.
      Participants' desires to see their expectancies confirmed were manipulated by
      making the target likable or unlikable. The authors hypothesized that when
      expectancy and liking "matched," participants would give significant weight to
      their expectancies at retrieval, resulting in expectancy-congruent distortion of
      the midterm grades. However, when expectancy and liking were "mismatched,"
      expectancies would be discontinued, and participants would show little or no
      expectancy-congruent distortion. Results supported these predictions. Study 2
      varied the order of the expectancy and liking information. Order affected the
      process by which mismatch participants discounted their expectancies. Results
      demonstrate that motivations not only may bias memory search but also may affect
      the reconstruction of existing memory traces.

PMID- 9008372
TI  - Terror management theory and self-esteem: evidence that increased self-esteem
      reduces mortality salience effects.
AB  - On the basis of the terror management theory proposition that self-esteem
      provides protection against concerns about mortality, it was hypothesized that
      self-esteem would reduce the worldview defense produced by mortality salience
      (MS). The results of Experiments 1 and 2 confirmed this hypothesis by showing
      that individuals with high self-esteem (manipulated in Experiment 1;
      dispositional in Experiment 2) did not respond to MS with increased worldview
      defense, whereas individuals with moderate self-esteem did. The results of
      Experiment 3 suggested that the effects of the first 2 experiments may have
      occurred because high self-esteem facilitates the suppression of death constructs
      following MS.

PMID- 9008373
TI  - The gender gap in occupational role attainment: a social dominance approach.
AB  - The authors present archival evidence that men disproportionately hold
      occupational roles that enhance group-based inequality and that women
      disproportionately hold roles that attenuate group-based inequality. The authors
      found evidence for 3 processes that may contribute to this pattern: self
      selection that is based on gender-linked differences in support for group
      inequality (social dominance orientation), hiring biases that are based on
      matching job applicants' group equality values with the hierarchy function of the
      job, and gender-stereotyped hiring biases. These processes were found across a
      number of occupations and participant variables. The social systems nature of
      these processes and the implications of the results for theoretical
      understandings of gender roles, social inequality, and theories of stereotyping
      are discussed.

PMID- 9008374
TI  - When exemplification fails: hypocrisy and the motive for self-integrity.
AB  - Two experiments investigated how the dissonance that follows a hypocritical
      behavior is reduced when 2 alternatives are available; a direct strategy
      (changing behavior to make it less hypocritical) or an indirect strategy (the
      affirmation of an unrelated positive aspect of the self). In Experiment 1, after
      dissonance was aroused by hypocrisy, significantly more participants chose to
      reduce dissonance directly, despite the clear availability of a self-affirmation
      strategy. In Experiment 2, participants again chose direct resolution of their
      hypocritical discrepancy, even when the opportunity to affirm the self held more
      importance for their global self-worth. The discussion focuses on the mechanisms
      that influence how people select among readily available strategies for
      dissonance reduction.

PMID- 9008375
TI  - Meta-accuracy among acquainted individuals: a social relations analysis of
      interpersonal perception and metaperception.
AB  - Meta-accuracy, knowing how others view the self, was examined using the Social
      Relations Model. Fifteen groups of 4-6 acquainted individuals gave self-ratings,
      perceptions of other group members, and estimated others' perceptions of self
      (metaperceptions) on the Big Five and Interesting. Individuals also rated liking
      and metaperceptions of liking. Trait perceptions were consensual, and self-other
      agreement emerged for most traits. Affect judgments were entirely relational;
      individuals differentiated among targets. Trait metaperceptions were dominated by
      perceiver variance. Individuals differed in the impression they believed others
      generally held about them. Affect metaperceptions, however, were relational in
      nature. Correlations between perceptions and metaperceptions assessed 2 types of
      meta-accuracy. Generalised meta-accuracy was obtained for some trait ratings.
      Affect judgments revealed significant dyadic meta-accuracy.

PMID- 9008376
TI  - Empathy and attitudes: can feeling for a member of a stigmatized group improve
      feelings toward the group?
AB  - Results of 3 experiments suggest that feeling empathy for a member of a
      stigmatized group can improve attitudes toward the group as a whole. In
      Experiments 1 and 2, inducing empathy for a young woman with AIDS (Experiment 1)
      or a homeless man (Experiment 2) led to more positive attitudes toward people
      with AIDS or toward the homeless, respectively. Experiment 3 tested possible
      limits of the empathy-attitude effect by inducing empathy toward a member of a
      highly stigmatized group, convicted murderers, and measuring attitudes toward
      this group immediately and then 1-2 weeks later. Results provided only weak
      evidence of improved attitudes toward murderers immediately but strong evidence
      of improved attitudes 1-2 weeks later.

PMID- 9008377
TI  - Gender and perceived pay entitlement: testing for effects of experience with
      income.
AB  - This article reports on 2 studies where variations on a research design from the
      literature on gender and perceived pay entitlement were used to test for effects
      of past pay experience and salience of the pay experience for the participants.
      In Study 1, level of previous income was not a predictor of self-payment behavior
      for women or men, and men allocated more pay to themselves than did women. In
      Study 2, women and men did not differ on perceived entitlement when the income
      and work experience were made salient, but they did in the nonsalient condition,
      as in Study 1. Also, past income and self-pay were positively correlated for
      women in the salient condition. Further, when the data from Study 1 and Study 2
      from the same condition (past income nonsalient) were combined, those with the
      higher previous income level paid themselves more than others, among both men and
      women.

PMID- 9008378
TI  - Escalation in response to persistent annoyance: groups versus individuals and
      gender effects.
AB  - Reactions to persistent annoyance were studied with a new laboratory method. A
      standard escalation sequence was found, which involved the following order of
      tactics: requests for termination of the annoyance, impatient demands,
      complaints, angry statements, threats, harassment, and abuse. The further along a
      tactic was in this sequence, the fewer the people who used it. This pattern of
      results provided a good fit to a cascading Guttman scale, suggesting the
      existence of a standard "try-try-again" escalation script. Problem solving and
      appeals to a third party were intermediate in the escalation sequence but did not
      appear to be part of the standard script. Groups used more escalated tactics than
      individuals, apparently because of their greater activity level. Women used more
      escalated tactics than men, at least in part because of greater anger at being
      treated unfairly. Men were the targets of more escalated tactics than women.

PMID- 9008379
TI  - Environmental predictors of personality differences: a twin and sibling study.
AB  - Nonshared environmental influences have consistently been shown to account for at
      least as much of the variance in personality as genetic factors, but the nature
      of these nonshared influences has largely remained unidentified. To identify
      environmental predictors of differential personality development, the Personality
      Research Form and 4 measures of people's perceptions of their background
      environments were administered to 143 adult twin pairs (93 monozygotic [MZ] and
      50 dizygotic [DZ] and 66 pairs of same-sex nontwin (NT) siblings. Differences
      between MZ twins, DZ twins, and NT siblings in a number of dimensions of
      personality were significantly related to differences on the environmental
      measures, and phenotypic correlations between the personality and environment
      measures were themselves entirely attributable to correlated nonshared
      environmental effects.

PMID- 9008380
TI  - Cognitive reactions to smoking relapse: the reciprocal relation between
      dissonance and self-esteem.
AB  - Perceptions of health risk associated with smoking, commitment to quitting, and
      self-concept were assessed among smokers before, during, and after their
      participation in cessation clinics. Consistent with expectations derived from
      cognitive dissonance theory, results indicated that relapsers' perception of risk
      declined after they resumed smoking, although the decline was significant only
      for relapsers with high self-esteem; high self-esteem relapsers experienced a
      significantly greater decline in commitment to quitting than did low self-esteem
      relapsers; and decline in risk perception among relapsers was associated with
      maintenance of self-esteem. The implications of these results for dissonance
      theory and the study of smoking relapse and cessation are discussed.

PMID- 9008381
TI  - Can personality explain genetic influences on life events?
AB  - Previous research in the Swedish Adoption/Twin Study of Aging (SATSA) has found
      genetic influences on life events (R. Plomin, P. Lichtenstein, N.L. Pedersen,
      G.E. McClearn, & J.R. Nesselroade, 1990). The present study extends this finding
      by examining sex differences in genetic and environmental contributions to life
      events and by examining personality as a mediator of genetic influences on life
      events in SATSA. Analyses were based on 320 twin pairs, including identical and
      fraternal twins reared together and apart (mean age = 58.6 years). Controllable,
      desirable, and undesirable life events were revealed significant genetic variance
      for women. There was no significant genetic variance for either sex for
      uncontrollable events. Multivariate analyses of personality (as indexed by
      Neuroticism, Extraversion, and Openness to Experience) and life events suggest
      that all of the genetic variance on controllable, desirable, and undesirable life
      events for women is common to personality. Thus, in this sample of older adult
      women, genetic influences on life events appear to be entirely mediated by
      personality.

PMID- 9008382
TI  - Genetic and environmental architecture of human aggression.
AB  - A meta-analysis was performed on data from 24 genetically informative studies by
      using various personality measures of aggression. There was a strong overall
      genetic effect that may account for up to 50% of the variance in aggression. This
      effect was not attributed to methodological inadequacies in the twin or adoption
      designs. Age differences were important. Self-report and parental ratings showed
      genes and the family environment to be important in youth; the influence of genes
      increased but that of family environment decreased at later ages. Observational
      ratings of laboratory behavior found no evidence for heritability and a very
      strong family environment effect. Given that almost all substantive conclusions
      about the genetics of personality have been drawn from self or parental reports,
      this last finding has obvious and important implications for both aggression
      research in particular and personality research.

PMID- 9008384
TI  - Do the structures of cell wall polysaccharides define their mode of synthesis?

PMID- 9008383
TI  - Stability in extraversion and aspects of social support at midlife.
AB  - This investigation used participants from the University of North Carolina Alumni
      Heart Study in an exploration of extraversion and aspects of social support at
      midlife. Results indicated that extraversion measured at college entry and at
      midlife was positively correlated with social activity and perceived social
      support measured later in middle adulthood. Multiple regression correlational
      analyses suggested that both the stable and changing components of extraversion
      influence structural and functional aspects of social support. Further, the
      changing component of extraversion was found to be significantly associated with
      greater social activity, perceived social support, and an increased likelihood of
      seeking support when faced with a stressful problem in middle adulthood. Overall,
      the development of sociability and outgoingness in interpersonal relationships
      during adolescence and young adulthood is suggested to be an important antecedent
      of the structural characteristics and functional dynamics of social support at
      midlife.

PMID- 9008385
TI  - Genetic dissection of acquired resistance to disease.

PMID- 9008386
TI  - Cell-specific expression of the promoters of two nonlegume hemoglobin genes in a
      transgenic legume, Lotus corniculatus.
AB  - The promoters of the hemoglobin genes from the nitrogen-fixing tree Parasponia
      andersonii and the related nonnitrogen-fixing Trema tomentosa both confer beta
      glucuronidase reporter gene expression to the central zone of the nodules of a
      transgenic legume, Lotus corniculatus. beta-Glucuronidase expression was high in
      the uninfected interstitial cells and parenchyma of the surrounding boundary
      layer and was low in the Rhizobium-infected cells. This contrasts with the
      expression of both the P. andersonii hemoglobin protein in P. andersonii nodules
      and the endogenous Lotus leghemoglobins that are expressed in the infected cells
      at very high levels. The expression pattern of the P. andersonii and T. tomentosa
      hemoglobin promoters in L. corniculatus resembles that of a nonsymbiotic
      hemoglobin gene from Casuarina glauca, which was introduced into this legume, and
      suggests that only the nonsymbiotic functions of the P. andersonii promoter are
      being recognized. Deletion of the distal segments of both the P. andersonii and
      T. tomentosa promoters identified regions important for the control of their
      tissue-specific and temporal activity in Lotus. Potential regulatory elements,
      which enhance nodule expression and suppress nonnodule expression, were also
      identified and localized to a distal promoter segment. A proximal AAGAG motif is
      present in the P. andersonii, T. tomentosa, and nonsymbiotic Casuarina hemoglobin
      genes. Mutation of this motif in the P. andersonii promoter resulted in a
      significant reduction in both the nodule and root expression levels in L.
      corniculatus. Some of the regulatory motifs characterized are similar to, but
      different from, the nodulin motifs of the leghemoglobins.

PMID- 9008387
TI  - Isolation and regulation of accumulation of a minor chromoplast-specific protein
      from cucumber corollas.
AB  - The differentiation of chloroplasts to chromoplasts in cucumber (Cucumis sativus
      L.) corollas parallels flower development. Chromoplast biogenesis involves
      chlorophyll degradation, carotenoid accumulation, and the appearance of a new set
      of proteins. To study factors involved in chromoplast biogenesis in floral
      tissues, a minor (in abundance) protein of about 14 kD, CHRD (chromoplast protein
      D), was isolated from cucumber corolla chromoplasts. Immunological
      characterization revealed that the protein is chromoplast-specific and that its
      steady-state level in corollas increases in parallel to flower development. The
      protein was not detected in cucumber leaves or fruits. Immunological analysis of
      corollas and fruits from variety of other plants also did not reveal cross
      reactivity with the CHRD protein antisera. Using an in vitro bud culture system,
      we analyzed the effect of phytohormones on CHRD expression. Gibberellic acid
      rapidly enhanced, whereas paclobutrazol down-regulated, the steady-state level of
      CHRD. Ethylene also down-regulated the protein's steady-state level. It is
      suggested that hormonal control of chromoplastogenesis is tightly regulated at
      the tissue/organ level and that mainly developmental signals control carotenoid
      accumulation in nonphotosynthetic tissues.

PMID- 9008388
TI  - Molecular cloning of 4-coumarate:coenzyme A ligase in loblolly pine and the roles
      of this enzyme in the biosynthesis of lignin in compression wood.
AB  - Two genomic sequences encoding 4-coumarate:coenzyme A ligase (4CL; EC 6.2.1.12)
      in loblolly pine (Pinus taeda L.) were cloned. Both sequences contained three
      introns and four exons with identical coding sequences predicting 537 amino
      acids. Two of the three introns in these two clones were different both in
      sequence and in length. Sequences of both 4CL clones were found in all nine
      megagametophyte DNAs tested, providing genetic evidence that these two 4CL
      genomic sequences are nonallelic genes. Our analyses suggest that there are at
      least two distinct, intron-containing 4CL genes, at least one of which is
      transcribed into 4CL mRNA in developing xylem tissue of loblolly pine. The levels
      of 4CL gene transcription in xylem were influenced by compressional stress,
      resulting in an elevated 4CL enzyme activity with 4-coumaric acid. 4CL enzyme
      activity with ferulic acid remained unchanged, whereas with caffeic acid it was
      significantly inhibited. Exogenously applied trans-cinnamic acid in the protein
      extracts from normal wood xylem caused inhibition of 4CL activity toward caffeic
      acid similar to that under compressional stress. The implications of this
      cinnamic acid-modulated effect on 4CL enzyme activities toward different
      substrates in regulating monolignol synthesis in xylem under compressional stress
      are discussed.

PMID- 9008389
TI  - Targeting of the Arabidopsis homomeric acetyl-coenzyme A carboxylase to plastids
      of rapeseeds.
AB  - Acetyl-coenzyme A carboxylase (ACCase) occurs in at least two forms in rapeseed
      (Brassica napus): a homomeric (HO) and presumably cytosolic isozyme and a
      heteromeric, plastidial isozyme. We investigated whether the HO-ACCase of
      Arabidopsis can be targeted to plastids of B. napus seeds. A chloroplast transit
      peptide and the napin promoter were fused to the Arabidopsis ACC1 gene and
      transformed into B. napus, with the following results. (a) The small subunit
      transit peptide was sufficient to provide import of this very large protein into
      developing seed plastids. (b) HO-ACCase in isolated plastids was found to be
      biotinylated at a level comparable to extraplastidial HO-ACCase. (c) In vitro
      assays of HO-ACCase in isolated plastids from developing seeds indicate that it
      occurs as an enzymatically active form in the plastidial compartment. (d) ACCase
      activity in mature B. napus seeds is normally very low; however, plants
      expressing the SSU/ACC1 gene had 10- to 20-fold higher ACCase activity in mature
      seeds, suggesting that plastid localization prevents the turnover of HO-ACCase.
      (e) ACCase over-expression altered seed fatty acid composition, with the largest
      effect being an increase approximately 5% by the expression of HO-ACCase in
      plastids.

PMID- 9008390
TI  - Characterization of a new antifungal chitin-binding peptide from sugar beet
      leaves.
AB  - The intercellular washing fluid (IWF) from leaves of sugar beet (Beta vulgaris
      L.) contains a number of proteins exhibiting in vitro antifungal activity against
      the devastating leaf pathogen Cercospora beticola (Sacc.). Among these, a potent
      antifungal peptide, designated IWF4, was identified. The 30-amino-acid residue
      sequence of IWF4 is rich in cysteines (6) and glycines (7) and has a highly basic
      isoelectric point. IWF4 shows homology to the chitin-binding (hevein) domain of
      chitin-binding proteins, e.g. class I and IV chitinases. Accordingly, IWF4 has a
      strong affinity to chitin. Notably, it binds chitin more strongly than the chitin
      binding chitinases. A full-length IWF4 cDNA clone was obtained that codes for a
      preproprotein of 76 amino acids containing an N-terminal putative signal peptide
      of 21 residues, followed by the mature IWF4 peptide of 30 residues, and an acidic
      C-terminal extension of 25 residues. IWF4 mRNA is expressed in the aerial parts
      of the plant only, with a constitutive expression in young and mature leaves and
      in young flowers. No induced expression of IWF4 protein or mRNA was detected
      during infection with C. beticola or after treatment with 2,6
      dichloroisonicotinic acid, a well-known inducer of resistance in plants.

PMID- 9008391
TI  - Expression and RNA splicing of the maize glutathione S-transferase Bronze2 gene
      is regulated by cadmium and other stresses.
AB  - The Bronze2 (Bz2) gene in maize (Zea mays) encodes a glutathione S-transferase
      that performs the last genetically defined step in anthocyanin biosynthesis-
      tagging anthocyanin precursors with glutathione, allowing for recognition and
      entry of anthocyanins into the vacuole. Here we show that Bz2 gene expression is
      highly induced by heavy metals such as cadmium. Treatment of maize seedlings with
      cadmium results in a 20-fold increase in Bz2 message accumulation and a 50-fold
      increase in the presence of the unspliced, intron-containing transcript. The
      increase in message levels during cadmium stress appears to result, at least in
      part, from activation of an alternative mRNA start site approximately 200
      nucleotides upstream of the normal start site; this site is not used in
      unstressed or heat-stressed tissues. The effect of cadmium on the RNA splicing of
      Bz2 seems to be specific: splicing of other intron-containing maize genes,
      including a maize actin gene under the control of the cadmium-inducible Bz2
      promoter, is unaffected by cadmium stress. Conversely, Bz2 intron splicing is not
      affected by other stress conditions that induce Bz2 gene expression, such as
      abscisic acid, auxin, or cold stress. Surprisingly, the increase in Bz2 mRNA
      during cadmium stress does not result in an increase in Bz2 glutathione S
      transferase activity. We propose that an alternative protein may be encoded by
      Bz2 that has a role during responses to heavy metals.

PMID- 9008392
TI  - Immunopurification and characterization of a 40-kD 1-aminocyclopropane-1
      carboxylic acid N-malonyltransferase from mung bean seedling hypocotyls.
AB  - 1-Aminocyclopropane-1-carboxylic acid (ACC) N-malonyltransferase catalyzes the
      transfer of the malonyl group from malonyl coenzyme A to ACC to form malonyl ACC.
      Using partially purified ACC N-malonyltransferase from the hypocotyls of mung
      bean (Vigna radiata) seedlings, we produced two mouse monoclonal antibodies (1H5
      and 2G3) to this enzyme. These antibodies bind to sites other than the active
      site of the enzyme because monoclonal antibody-bound ACC N-malonyltransferase
      still exhibits full catalytic activity. A monoclonal antibody column was
      constructed using 1H5 and protein G Sepharose. The ACC N-malonyltransferase
      purified from this monoclonal antibody column has a molecular mass of 40 kD,
      which is different from that reported previously. The enzyme has a higher
      electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis in the absence of the reducing agent dithiothreitol. The optimum
      temperature of this 40-kD ACC N-malonyltransferase is 45 degrees C and the
      apparent Kms for ACC and malonyl coenzyme A are 66.7 and 40 microns,
      respectively.

PMID- 9008393
TI  - Maize phenylalanine ammonia-lyase has tyrosine ammonia-lyase activity.
AB  - A full-length cDNA encoding phenylalanine ammonia-lyase (PAL) from Zea mays L.
      was isolated and the coding region was expressed in Escherichia coli as a C
      terminal fusion to glutathione S-transferase. After purification by glutathione
      Sepharose chromatography, the glutathione S-transferase moiety was cleaved off
      and the resulting PAL enzyme analyzed. In contrast to PAL from dicots, this maize
      PAL isozyme catalyzed the deamination of both L-phenylalanine (PAL activity) and
      L-tyrosine (tyrosine ammonia-lyase activity). These results provide unequivocal
      proof that PAL and tyrosine ammonia-lyase activities reside in the same
      polypeptide. In spite of large differences in the Michaelis constant and turnover
      number of the two activities, their catalytic efficiencies are very similar.
      Also, both activities have the same pH and temperature optima. These results
      imply that maize can produce p-coumaric acid from both phenylalanine and
      tyrosine.

PMID- 9008394
TI  - Inhibition of trehalase activity enhances trehalose accumulation in transgenic
      plants.
AB  - As a first step toward the exploitation of the disaccharide trehalose as a stress
      protective and preservative agent in plants, we engineered trehalose biosynthesis
      in tobacco (Nicotiana tabacum) and potato (Solanum tuberosum) by introducing the
      otsA and otsB genes from Escherichia coli, which encode trehalose-6-phosphate
      synthase and trehalose-6-phosphate phosphatase, respectively. In leaves of
      transgenic tobacco plants, very low levels of trehalose accumulation were
      obtained (0.11 mg g-1 fresh weight), whereas in transgenic potato tubers, no
      trehalose accumulated at all. Plant trehalase activity was shown to affect the
      accumulation of trehalose in these plants. An increase in trehalose accumulation,
      up to 0.41 and 4.04 mg g-1 fresh weight in tobacco leaves and potato micro
      tubers, respectively, was noted when the potent trehalase inhibitor validamycin A
      was added to in vitro plants and to hydroponically grown greenhouse plants.
      Stunted growth and the formation of lancet-shaped leaves by trehalose
      accumulating tobacco plants suggest a negative effect of trehalose biosynthesis
      on N. tabacum development. It is surprising that experiments with wild-type
      plants cultured in the presence of validamycin A indicate that, despite current
      belief, the capacity to synthesize trehalose may not be restricted to primitive
      phyla of vascular plants and certain "resurrection plants," but may exist
      throughout the angiosperms.

PMID- 9008395
TI  - Differential expression and properties of starch branching enzyme isoforms in
      developing wheat endosperm.
AB  - Three forms of starch branching enzyme (BE) from developing hexaploid wheat
      (Triticum aestivum) endosperm have been partially purified and characterized.
      Immunological cross-reactivities indicate that two forms (WBE-IAD, 88 kD, and WBE
      IB, 87 kD) are related to the maize BE I class and that WBE-II (88 kD) is related
      to maize BE II. Comparison of the N-terminal sequences from WBE-IAD and WBE-II
      with maize and rice BEs confirms these relationships. Evidence is presented from
      the analysis of nullisomic-tetrasomic wheat lines demonstrating that WBE-IB is
      located on chromosome 7B and that the WBE-IAD fraction contains polypeptides that
      are encoded on chromosomes 7A and 7D. The wheat endosperm BE classes are
      differentially expressed during endosperm development. WBE-II is expressed at a
      constant level throughout mid and late endosperm development. In contrast, WBE
      IAD and WBE-IB are preferentially expressed in late endosperm development.
      Differences are also observed in the kinetic characteristics of the enzymes. The
      WBE-I isoforms have a 2- to 5-fold higher affinity for amylose than does WBE-II,
      and the WBE-I isoforms are activated up to 5-fold by phosphorylated intermediates
      and inorganic phosphate, whereas WBE-II is activated only 50%. The potential
      implications of this activation of BE I for starch biosynthesis are discussed.

PMID- 9008396
TI  - Multiple forms of ADP-glucose pyrophosphorylase from tomato fruit.
AB  - ADP-glucose pyrophosphorylase (AGP) was purified from tomato (Lycopersicon
      esculentum Mill.) fruit to apparent homogeneity. By sodium dodecyl sulfate
      polyacrylamide gel electrophoresis the enzyme migrated as two close bands with
      molecular weights of 50,000 and 51,000. Two-dimensional polyacrylamide gel
      electrophoresis analysis of the purified enzyme, however, revealed at least five
      major protein spots that could be distinguished by their slight differences in
      net charge and molecular weight. Whereas all of the spots were recognized by the
      antiserum raised against tomato fruit AGP holoenzyme, only three of them reacted
      strongly with antiserum raised against the potato tuber AGP large subunit, and
      the other two spots (with lower molecular weights) reacted specifically with
      antisera raised against spinach leaf AGP holoenzyme and the potato tuber AGP
      small subunit. The results suggest the existence of at least three isoforms of
      the AGP large subunit and two isoforms of the small subunit in tomato fruit in
      vivo. The native molecular mass of the enzyme determined by gel filtration was
      220 +/- 10 kD, indicating a tetrameric structure for AGP from tomato fruit. The
      purified enzyme is very sensitive to 3-phosphoglycerate/inorganic phosphate
      regulation.

PMID- 9008398
TI  - The electronic Plant Gene Register.

PMID- 9008399
TI  - [IX meeting of the Society of Public Health of Catalunya and Balears. Lloret de
      Mar, 18-19 October 1996. Abstracts].

PMID- 9008400
TI  - Keio University International Symposia for Life Sciences and Medicine. 1996
      Conference on Oxygen Homeostasis and its Dynamics. Tokyo, Japan, December 8-13,
      1996. Abstracts.

PMID- 9008397
TI  - Plant 21D7 protein, a nuclear antigen associated with cell division, is a
      component of the 26S proteasome.
AB  - Previously, we cloned a carrot (Daucus carota L.) cDNA encoding a 45-kD protein,
      21D7, located in the nuclei of proliferating cells. The 21D7 protein is similar
      to the partial sequence of a regulatory subunit of the bovine 26S proteasome, p58
      (G. DeMartino, C.R. Moomaw, O.P. Zagnitko, R.J. Proske, M. Chu-Ping, S.J.
      Afendis, J.C. Swaffield, C.A. Slaughter [1994] J Biol Chem 269: 20878-20884) and
      to the deduced sequence encoded by the Saccharomyces cerevisiae gene SUN2 (M.
      Kawamura, K. Kominami, J. Takeuchi, A. Toh-e [1996] Mol Gen Genet 251: [146
      152]). In our work, the expression of plant 21D7 cDNA rescued the yeast sun2
      mutant. Fractionation of carrot and spinach (Spinacia oleracea L.) crude extracts
      showed that the 21D7 protein sedimented with the active 26S proteasomes. The
      cessation of cell proliferation in carrot suspensions at the stationary phase
      caused 26S proteasome dissociation and, correspondingly, the 21D7 protein
      sedimented together with the free regulatory complexes of the 26s proteasomes.
      Large-scale purification of carrot 26s proteasomes resulted in co-isolation of
      the 21D7 protein. Polyacrylamide gel electrophoresis under nondenaturing
      conditions showed that the 21D7 protein had the same mobility as the 26S
      proteasome and that proteasome dissociation changed the mobility of the 21D7
      protein accordingly. We conclude that the 21D7 protein is a subunit of the plant
      26S proteasome and that it probably belongs to the proteasome regulatory complex.

PMID- 9008401
TI  - Changes of bromopropylate and carbendazim residues during processing of apples
      into apple puree.
AB  - The study of changes of bromopropylate and carbendazim residues during apple
      processing was carried out. It was stated that bromopropylate residues on apples
      before and after washing stayed at similar levels (0.024 mg/kg) and then dropped
      by 60% during apple processing, while those of carbendazim remained at the level
      of 0.10 mg/kg during the whole process.

PMID- 9008402
TI  - First isolation of Microsporum racemosum Borelli in Poland.
AB  - During a study of keratinolytic fungi in the ash heap ground, considerably
      influenced by the municipal landfill site, a rare potentially pathogenic
      dermatophyte, Microsporum racemosum Borelli, was recognized. This is the first
      report on its isolation in Poland. Morphological and ecological features of the
      fungus are discussed.

PMID- 9008404
TI  - Electrochemical studies of zinc in zinc-insulin solution.
AB  - The electrochemical determination of zinc arising from zinc-insulin complexes was
      investigated and it was demonstrated that zinc in zinc-insulin solution can be
      measured in the presence of dissolved oxygen by square-wave anodic stripping
      voltammetry (SWASV) at mercury thin-film electrodes on glassy carbon disc
      minielectrode and cylindrical carbon fibre microelectrode substrates. Reoxidation
      signals arise from complexed zinc at low insulin concentrations (< 100 nmol l-1)
      and from labile zinc at higher concentrations; the latter can be quantified
      through linear calibration curves. Batch injection analysis with SWASV was
      successfully tested for the determination of zinc in zinc-insulin solutions in
      small sample volumes. Since intracellularly stored insulin exists in the form of
      a zinc-insulin complex, these techniques are very promising for the indirect
      study of insulin release from pancreatic beta-cells.

PMID- 9008403
TI  - The importance of diabetes registries and clinical biology for the study and
      treatment of type 1 (insulin-dependent) diabetes mellitus.
AB  - The Belgian Diabetes Registry (BDR) has studied the epidemiology of Type 1
      diabetes with clinical onset before age 40 years in the Antwerp district. Both in
      the age categories 0-14 years and 15-39 years, the incidence approximates 10 new
      cases per 100,000 inhabitants per years. Most patients are adults. Juvenile-onset
      diabetic patients who were so far more intensively studied must therefore not be
      considered as "prototypes" for the disease, but rather represent "atypical" cases
      with rapid evolution. Participation in international programs (EURODIAB ACE,
      DIAMOND) has characterized the incidence of Type 1 diabetes in Belgium as being
      intermediate between values in low-incidence regions (5 to 10 cases/100,000
      inhabitants/yr such as in parts of Southern or Eastern Europe) and values in high
      incidence regions 30 to 40 cases/100,000 inhabitants/yr such as in Finland and
      Sardinia). Type 1 diabetes is a heterogenous disease in terms of clinical
      presentation, etiological factors and biological markers. Clinical and
      fundamental research on Type 1 diabetes needs to study patient groups which
      faithfully reflect this heterogeneity. This is best achieved by recruiting
      patients through diabetes registries. In Belgium, the BDR presently registers
      about 40% of all new cases of Type 1 diabetes with onset before age 40 years.
      Until now, more than 1700 patients and about 1100 first degree relatives are
      registered. This group is representative of the Belgian population of Type 1
      diabetic patients with onset before age 40 years. High quality-assays for immune
      and genetic markers of Type 1 diabetes were designed and validated through
      repeated participation in international quality control programs. By
      systematically performing these assays on the representative non-selected samples
      of BDR-patients, it became possible to further clarify the clinical biology of
      Type 1 diabetes and to demonstrate hitherto unrecognized associations among
      disease markers. Certain of these markers (insulin auto-antibodies, IAA; islet
      cell antibodies, ICA; HLA DQA1*0301-DQB1*0302 risk haplotype) are more frequent
      for clinical onset before age 10 years and appear associated in that age
      category. Other markers (glutamate decarboxylase antibodies; GAD-Ab) occur more
      frequently at onset between age 10 and 40 years, where they are preferentially
      associated with increased genetic risk. Yet another genetic marker (1/1
      susceptibility genotype in the 5' polymorphic region of the insulin gene) occurs
      regardless of age and presence of auto-antibodies, preferentially in patients
      without the highest HLA-linked genetic risk. Age-dependent differences in marker
      frequency and -associations possibly reflect age-dependent differences in
      etiological factors, in order of appearance of biological markers, or in
      progression rate of the disease. Presently, more than 90% of the patients under
      age 40 years carry at least one diabetes-associated immune or genetic marker,
      which opens perspectives for a better classification of the disease, especially
      in adults. Preliminary follow-up studies in first-degree relatives of registered
      patients confirm the diabetes-predictive value of the markers studied. A group of
      subjects at high risk for the disease could thus be identified. These subjects
      qualify for participation in preventive intervention trials. In this respect BDR
      officially represents Belgium in several international programs: EURODI-AB ACE
      for marker-studies, ICARUS for diabetes prediction, ENDIT for diabetes-prevention
      and GETREM for optimal diabetes treatment. This collaboration will focus in the
      near future on neonatal screening and follow-up, objective classification
      criteria for diabetes in adults, refined diabetes-prediction and preventive
      intervention studies. BDR may also serve as a tool for systematic research on the
      complications, innovative treatments and socio-economical aspects of diabetes.

PMID- 9008405
TI  - Sensitive and specific electrochemical sensors for charge-diffuse cations: use of
      lipophilic cyclodextrins and an enzyme relay for the determination of
      acetylcholine.
AB  - Lipophilic, alkylated cyclodextrins (CDs) are aromatic hosts which are excellent
      ionophores for reversibly binding size-matched, charge-diffuse cations. The
      application of lipophilic beta-CDs as ionophores for sensing acetylcholine
      chloride using a potentiometric ISE and an amperometric biosensor is described.
      Potentiometric ISEs, using 2,6-didodecyl-beta-CD as ionophore, showed a Nernstian
      response with a limit of detection -log[C] = 5.0 and selectivity coefficient 
      logKijPot = 4.2 (in serum levels of Na+, K+ and Ca2+). A Nernstian response is
      maintained in the presence of bovine serum albumin for a PVC- and a polyurethane
      based electroactive membrane on initial contact. However, on prolonged contact,
      the polyurethane-based membranes showed a lower shift in Einitial0 (the bias
      potential on initial contact with analyte solution) than PVC. Amperometric
      biosensors were assembled by modifying screen-printed electrodes with a
      ferrocenyl charge shuttle, enzymes (horseradish peroxidase, choline oxidase
      and/or acetylcholine esterase) and a thin film comprising a polyurethane matrix,
      2,3,6-triethyl-beta-CD, a plasticizer and a large anionic salt. The resulting
      sensor, which was capable of detecting subpicomolar levels of acetylcholine, was
      highly specific and was stable to storage in air and in solution. Interference
      from endogenous electroactive compounds was minimal.

PMID- 9008407
TI  - Effect of different experimental parameters on the potentiometric evaluation of
      blood electrolytes using K+ as a test cation.
AB  - Potentiometric evaluation of ionic concentrations in physiological media has been
      reported to be significantly affected by the albumin containing matrix. Previous
      studies have attempted to clarify the origin of different patterns of variation
      of E versus albumin concentration at a constant 0.01 mol dm-3 KCl, depending on
      the experimental methodologies. This paper reports on measurements of K+ in
      albumin (BSA) containing KCl solutions, which have been pursued following
      different methodologies concerning the sequence of measurements, i.e., starting
      either from the most concentrated solution (100 g dm-3) (A) or from the most
      dilute solution (20 g dm-3) (B), and solution preparation, (a) dilution of an
      initial 100 g dm-3 albumin solution by successive addition of 0.01 mol dm-3 KCl,
      (b) concentration of an initial 20 g dm-3 albumin solution by addition of solid
      substance, (c) independent preparation of each albumin solution (20, 40, 60, 80
      and 100 g dm-3) or (d) preparation of each albumin solution from direct dilution
      of a 100 g dm-3 stock solution with 0.01 mol dm-3 KCl. Convenient calculations
      were made and showed a significant contribution of albumin to the liquid-liquid
      junction potential. The variation of potential with albumin concentration is
      smaller for hypertonic than for isotonic bridge solutions, both for the dilution
      series (A,a and A,d) and for the concentration series (B,c and B,d). When the
      method for increasing the concentration is performed by addition of a solid
      substance to an initially diluted albumin (B,b), the slope of the E versus
      albumin concentration plot is larger for hypertonic than for isotonic reference
      electrolytes. This latter finding is in agreement with Payne's results when
      ultrafiltration was used to concentrate a protein solution. These observations
      are a clear indication that the method of preparation of concentrated protein
      solutions may significantly affect the results.

PMID- 9008406
TI  - Solid-phase extraction coupled with electrochemical detection for the
      determination of the herbicide bromofenoxim in water samples at low- and sub
      microgram l-1 levels.
AB  - The application of solid-phase extraction (SPE) as a preconcentration and clean
      up step with subsequent off-line flow injection amperometric (FI-AD) or batch
      square-wave voltammetric (SWV) detection of the herbicide bromofenoxim was
      developed. The selection of an appropriate organic eluent, some parameters
      influencing the efficiency of the SPE and the electrochemical detection of
      bromofenoxim in the organic effluent solution were thoroughly investigated.
      Undiluted acetonitrile with SWV and acetonitrile-water (80 + 20) with FI-AD, both
      containing 0.1 mol l-1 LiClO4, were chosen as the most appropriate SPE eluents.
      The addition of LiClO4 as supporting electrolyte to the eluent and acidification
      of a water sample to 1 x 10(-3) mol l-1 HClO4 (pH 3) prior to the SPE procedure
      were found to improve greatly the current response on mercury drop (SWV) and
      mercury film (FI-AD) electrodes. Subsequent to the SPE procedure, the effluents
      were transferred to the voltammetric cell or injected into the flow injection
      system without any further treatment. The calibration plots obtained for
      bromofenoxim in pure water samples were linear over the ranges 0.2-12.0
      micrograms l-1 and 3.0-120 micrograms l-1, with calculated detection limits of
      0.05 and 1.5 micrograms l-1 (100 ml samples), for the SPE-SWV and SPE-FI-AD
      procedures, respectively. The actual detection capabilities of the proposed
      methods depend on the water sample volumes applied to the extraction cartridges.
      The recoveries of the over-all procedures, applying spiked tap water samples, and
      the corresponding RSDs were 92% and 6% (n = 6) and 121% and 9% (n = 7) for SPE
      SWV and SPE-FI-AD, respectively. The practical applicability of the proposed
      methods for the analysis of ground and tap water samples was confirmed via an
      inter-laboratory test on a tap water sample containing five common pesticides
      including bromofenoxim.

PMID- 9008408
TI  - Influence of surface-active compounds on the response and sensitivity of
      cholinesterase biosensors for inhibitor determination.
AB  - The influence of non-ionogenic surfactants, i.e., Tween-20, Triton X-100 and PEG
      10,000, on the response of cholinesterase-based potentiometric biosensors and
      their sensitivity towards reversible and irreversible inhibitors were
      investigated. Acetyl- and butyrylcholinesterases were immobilized on nylon,
      cellulose nitrate films and tracing paper and were introduced into an assembly of
      potentiometric biosensors. The effect of surface-active compounds depends on the
      hydrophilic properties and porosity of the enzyme support material and the
      inhibition mechanism. In the range 0.002-0.3% m/v the surfactants show a
      reversible inhibiting effect on biosensor response. At lower concentrations (down
      to 10(-4)% m/v) the surfactants alter the analytical characteristics of
      reversible and irreversible inhibitor determination. The use of surface-active
      additives improves the biosensor selectivity in multi-component media.

PMID- 9008409
TI  - Sensitive densitometry for the determination of platelet-activating factor and
      other phospholipids in human tears.
AB  - A sensitive TLC method is reported for the determination of the platelet
      activating factor (PAF) and other phospholipids in human tears. Tear samples
      absorbed on filter-paper were subjected to diatomite column extraction with
      chloroform-methanol. The eluent containing phospholipids was spotted on a silica
      gel plate. After removing lipids other than phospholipids by pre-development with
      hexane-diethyl ether (4 + 1 v/v), individual phospholipid separation was carried
      out by development with chloroform-methanol-water (65 + 35 + 7 v/v).
      Phospholipase C and then alkaline phosphatase solutions were sprayed on the TLC
      plate at 45 degrees C to liberate phosphate from each phospholipid. By spray
      application of a mixture of ammonium molybdate and Malachite Green, the liberated
      phosphates appeared as blue-green spots of molybdophosphate-Malachite Green
      aggregate on a yellow-brown background. The absorbance of each spot on the plate
      was measured at 620 nm with a densitometer. The peak area was found to be
      linearly related to PAF content in the range 2-100 pmol per spot, the RSD being
      2% (n = 7). Approximately 86% of standard PAF added to tears was recovered. By
      this method, lysophosphatidylcholine (lysoPC), phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE) in human tears could also be detected with high
      sensitivity. Each phospholipid in healthy human tears showed a nearly constant
      content; PAF, lysoPC, PC and PE were present at levels of 26.2, 42.3, 10.0 and
      19.7%, respectively.

PMID- 9008410
TI  - Calcium biosensing with a sol-gel immobilized photoprotein.
AB  - Aequorin, the bioluminescent protein found in the jellyfish Aequorea sp., has
      been immobilized in a porous sol-gel glass environment. The luminescence from
      this protein is specifically triggered by the presence of calcium ions, thus
      offering exciting possibilities for the development of an optical biosensor for
      this cationic species. The luminescence emission spectrum has been measured from
      the aequorin protein after interaction with calcium ions. The intensity of the
      luminescence, measured at the peak maximum of 470 nm, for the encapsulated
      protein has been calibrated against calcium ion concentration. The
      characterization of the protein within the sol-gel matrix has been reported
      together with biosensing experiments using human sera and milk samples. The
      results suggest that the sol-gel encapsulated aequorin protein offers potential
      as a one shot bioluminescence based biosensor for the determination of calcium
      ions in such complex matrices.

PMID- 9008412
TI  - Adaptive mutation: a general phenomenon or special case?
AB  - A recent article by Galitski and Roth characterizes adaptive reversion of
      chromosomal lac- mutations in Salmonella typhimurium LT2. Using a classical
      genetic approach they show that adaptive reversion, as characterized by the
      appearance of late revertant colonies, is an exception rather than a general
      phenomenon for reversion of nonsense, missense, frameshift and insertion
      mutations. For certain mutations, however, the number of late revertants exceeds
      the predicted number. These excess revertants suggest that adaptive mutability is
      applicable to chromosomal genes as well as to genetic changes involving F
      plasmids and lysogenic phages.

PMID- 9008413
TI  - What does Mos do in oocytes and somatic cells?
AB  - Mos, a protein kinase, is specifically expressed and functions during meiotic
      maturation (or G2/M progression) of vertebrate oocytes. When expressed
      ectopically, however, it can also readily induce oncogenic transformation (or
      uncontrolled G1/S transitions) in somatic cells. In both of these cell types, Mos
      activates mitogen-activated protein kinase (MAPK), which seems largely to mediate
      its different functions in both oocyte maturation and cellular transformation. In
      oocyte maturation, the Mos-MAPK pathway probably serves to activate and stabilize
      M-phase promoting factor (MPF) (possibly by inhibiting some negative regulator(s)
      of this factor), while in cellular transformation, it seems to stabilize and
      activate the nuclear oncoprotein c-Fos as well as to induce transcription of its
      gene. Thus, the different functions of Mos in oocytes and somatic cells may arise
      chiefly from its different MAPK-mediated targets in the respective cell types.
      This review discusses the cellular basis that may enable Mos to act differently
      in oocytes and somatic cells.

PMID- 9008414
TI  - Synthesis and function of Mos: the control switch of vertebrate oocyte meiosis.
AB  - One distinguishing feature of vertebrate oocyte meiosis is its discontinuity;
      oocytes are released from their prophase I arrest, usually by hormonal
      stimulation, only to again halt at metaphase II, where they await fertilization.
      The product of the c-mos proto-oncogene, Mos, is a key regulator of this
      maturation process. Mos is a serine-threonine kinase that activates and/or
      stabilizes maturation-promoting factor (MPF), the master cell cycle switch,
      through a pathway that involves the mitogen-activated protein kinase (MAPK)
      cascade. Oocytes arrested at prophase I lack detectable levels of Mos, which must
      be synthesized from a pool of maternal mRNAs for proper maturation. While Mos is
      necessary throughout maturation in Xenopus, it seems to be required only for
      meiosis II in the mouse. The translational activation of c-mos mRNA at specific
      times during meiosis requires cytoplasmic polyadenylation. Cis- and trans-acting
      factors for polyadenylation are, therefore, essential elements of maturation.

PMID- 9008416
TI  - Integrin-mediated calcium signaling and regulation of cell adhesion by
      intracellular calcium.
AB  - Integrins are ubiquitous trans-membrane adhesion molecules that mediate the
      interaction of cells with the extracellular matrix (ECM). Integrins link cells to
      the ECM by interacting with the cell cytoskeleton. In cases such as leukocyte
      binding, integrins mediate cell-cell interactions and cell-ECM interactions.
      Recent research indicates that integrins also function as signal transduction
      receptors, triggering a number of intracellular signaling pathways that regulate
      cell behavior and development. A number of integrins are known to stimulate
      changes in intracellular calcium levels, resulting in integrin activation.
      Although changes in intracellular calcium regulate a vast number of cellular
      functions, this review will discuss the stimulation of calcium signaling by
      integrins and the role of intracellular calcium in the regulation of integrin
      mediated adhesion.

PMID- 9008415
TI  - PKC--a pivotal regulator of early development.
AB  - Oocytes, eggs and blastomeres of the embryo are special cells that undergo rapid
      changes in structure and function at developmental transitions. These changes are
      frequently regulated by cytoplasmic signaling events, particularly at the
      developmental transition of fertilization, because the genome is largely
      inactivated at this time. Protein kinase C (PKC) is a signaling agent that acts
      after the sperm-induced rise in calcium and has a central role in the remodeling
      of the structure of the egg into the zygote in many species. PKC also acts during
      other developmental transitions. This kinase serves as a chronometer, which can
      choreograph the cell's remodeling events in both space and time. Several
      technical advancements discussed in this review have permitted a better
      understanding of the actions of PKC.

PMID- 9008418
TI  - Histone acetylation: a possible mechanism for the inheritance of cell memory at
      mitosis.
AB  - Immunofluorescent labelling demonstrates that human metaphase chromosomes contain
      hyperacetylated histone H4. With the exception of the inactive X chromosome in
      female cells, where the bulk of histone H4 is underacetylated, H4
      hyperacetylation is non-uniformly distributed along the chromosomes and clustered
      in cytologically resolvable chromatin domains that correspond, in general, with
      the R-bands of conventional staining. The strongest immunolabelling is often
      found in T-bands, the subset of intense R-bands having the highest GC content.
      The majority of mapped genes also occurs in R-band regions, with the highest gene
      density in T-bands. These observations are consistent with a model in which
      hyperacetylation of histone H4 marks the position of potentially active gene
      sequences on metaphase chromosomes. Since acetylation is maintained during
      mitosis, progeny cells receive an imprint of the histone H4 acetylation pattern
      that was present on the parental chromosomes before cell division. Histone
      acetylation could provide a mechanism for propagating cell memory, defined as the
      maintenance of committed states of gene expression through cell lineages.

PMID- 9008419
TI  - FISH technology in chromosome and genome research.
AB  - Fluorescent in situ hybridization technology is one of the most exciting and
      versatile research tools to be developed in recent years. It has enabled research
      to progress at a phenomenal rate in diverse areas of basic research as well as in
      clinical medicine. Fluorescent in situ hybridization has applications in physical
      mapping, the study of nuclear architecture and chromatin packaging, and the
      investigation of fundamental principles of biology such as DNA replication, RNA
      processing, gene amplification, gene integration and chromatin elimination. This
      review highlights some of these areas and provides source material for the reader
      who seeks more information on a specific field.

PMID- 9008417
TI  - Peroxisome biogenesis.
AB  - Peroxisomes are eukaryotic organelles that are the subcellular location of
      important metabolic reactions. In humans, defects in the organelle's function are
      often lethal. Yet, relative to other organelles, little is known about how cells
      maintain and propagate peroxisomes or how they direct specific sets of newly
      synthesized proteins to these organelles (peroxisome biogenesis/assembly). In
      recent years, substantial progress has been made in elucidating aspects of
      peroxisome biogenesis and in identifying PEX genes whose products, peroxins, are
      essential for one or more of these processes. The most progress has been made in
      understanding the mechanism by which peroxisome matrix proteins are imported into
      the organelles. Signal sequences responsible for targeting proteins to the
      organelle have been defined. Potential signal receptor proteins, a receptor
      docking protein and other components of the import machinery have been
      identified, along with insights into how they operate. These studies indicate
      that multiple peroxisomal protein-import mechanisms exist and that these
      mechanisms are novel, not simply variations of those described for other
      organelles.

PMID- 9008420
TI  - Genetics of the susceptibility to infectious diseases. First Louis Pasteur
      Conference on Infectious Diseases, Paris, 21-23 October, 1996.

PMID- 9008421
TI  - Helicobacter pylori, individual host specificity and human disease. European
      Helicobacter Study Group Meeting, Copenhagen, October 16-19, 1996.

PMID- 9008422
TI  - Peer relations, loneliness, and self-perceptions in school-aged children.
AB  - Recent studies have suggested that certain behavioural characteristics in
      children are closely associated with peer acceptance, and that children who are
      not accepted by peers are more lonely than other children. The present research
      examines a more comprehensive pattern of relationships. In addition to
      behavioural characteristics, peer acceptance, and feelings of loneliness and
      social dissatisfaction, the study includes self-perceptions of social competence,
      self-esteem, and goal orientation (defensive ego-involvement). A theoretical
      model is presented to analyse predictive relations. The model was tested on a
      sample of 8th grade children (N = 96). Teacher and peer assessments of
      behavioural characteristics (humour, externalising, internalising and prosocial
      behaviour) were applied. In general, results were consistent with the proposed
      model. Loneliness was predicted by behavioural characteristics and low peer
      acceptance, and strong negative paths were found from loneliness to self-esteem
      and perceived social competence. Self-perceptions were not predicted by peer
      acceptance, and few direct paths were found from behavioural characteristics to
      self-perceptions. Thus loneliness has a mediating position between behaviour and
      peer acceptance on the one hand and self-perceptions on the other hand. This
      indicates that children's self-perceptions are affected by their socio-emotional
      reactions to peer difficulties and not directly by low peer acceptance. Strong
      negative paths were found from self-esteem and perceived social competence to
      defensive ego-involvement, which suggests that negative self-perceptions may have
      adverse consequences for children's goal orientations. Practical implications of
      the findings are discussed.

PMID- 9008423
TI  - Assessment of bully/victim problems in 8 to 11 year-olds.
AB  - The aim of the present study was to develop two six-item self-report scales (the
      Bullying-Behaviour Scale and the Peer-Victimisation Scale) to assess bully-victim
      problems at school. These scales were designed so that they could be immersed
      within the Self-Perception Profile for Children (SPPC: Harter, 1985) thus
      reducing the saliency of the items. Internal reliability of both scales was found
      to be satisfactory (Cronbach's alpha = 0.83 and 0.82 respectively). Data are
      reported on the association between scores on both scales and scores on the SPPC
      and the Birleson Depression Inventory (Birleson, 1981) with 425 children (204
      boys and 221 girls) ranging from 8 to 11 years (mean = 9.2 years). Forty-six per
      cent of the children were classified as bullies, victims, or both: 22 per cent
      were classified as victims only, 15 per cent as bully/victims, and 9 per cent as
      bullies only.

PMID- 9008424
TI  - How do Finnish students prepare for their future in three school types? The
      relation between content of plans, information gathering and self-evaluations.
AB  - The effect of gender and school type on Swedish speaking Finnish students'
      information gathering for the future and self-evaluation was investigated in a
      study, in which 15-year-old comprehensive school students and 18-year-old upper
      secondary school and vocational school students (N = 460) served as samples. It
      was observed that girls generally reported more information gathering than boys
      did, about three content areas, mostly concerning future education and
      occupation, and less concerning family life. Girls also reported more information
      gathering in all contexts except formal education, than boys. Home was reported
      as the most used source of knowledge, next came peers and school friends; mass
      media and formal education were the least used source. Formal education was
      emphasised by comprehensive school students, and mass media by upper secondary
      school students. Generalisation of more reported information gathering across
      contexts was more typical of girls, while generalisation of less information
      gathering was more typical of boys. Limited relationships between self
      evaluation, measured as self-esteem, certainty of goal realisation and school
      achievement, and information gathering were found. It is suggested that informal
      learning of cultural knowledge is a more powerful mediator of future preparation
      than formal education.

PMID- 9008425
TI  - Do levels of interest have an effect on children's comprehension monitoring
      performance?
AB  - This study examines the effect of interest levels on the comprehension monitoring
      ability of 8- and 9-year-old children. Two groups participated in the study; they
      were matched for single-word reading and vocabulary skills, but differed in
      comprehension skill. Two tests were carried out which required the children to
      read a number of brief passages, some of which contained embedded problems. The
      children's task was to identify the problems. Test 2 was game-like in nature and
      the children reported finding it more interesting than Test 1. Interest level was
      found to affect test performance in the poor comprehenders' comprehension
      monitoring: a significant improvement in their performance was found at high
      interest levels (Test 2). However, the performance of the good comprehenders was
      independent of interest level. This study suggests that the comprehension
      monitoring deficit in the poor comprehenders is not irreversible, and is likely
      to be related to poor motivation and low levels of interest. The implications for
      remedial education are discussed.

PMID- 9008426
TI  - Counting and cardinality in English nursery pupils.
AB  - This study examines the development of counting and cardinality in a structured
      sample of 60 English 3 1/2-4 1/2 year-olds attending local education authority
      nursery classes in socially mixed areas of Portsmouth. Children were given two
      types of task: counting sets of animals, and giving specified numbers of items
      from a pile. Three measures of cardinal understanding were used: spontaneous
      repetition of the last word on completion of a counting trial, repetition of the
      last word in reply to a question, and use of counting vs. grabbing when asked to
      give a specific number of items from a heap. In line with research on other
      populations the results indicate a pronounced developmental discrepancy between
      procedural and conceptual knowledge of counting, but cardinality appears to
      develop six months later in this population than in other populations studied.
      There were marked individual differences, however. Proficiency with object
      counting was found to be necessary, but not sufficient, for cardinal
      understanding. Children rarely repeated final count words spontaneously. Last
      word repetition in response to a verbal prompt depended on the nature of the
      prompt. Contrary to previous research, the present results indicate that last
      word repetition elicited by the prompt 'how many?' is not merely a conventional
      reply but generally implies an understanding of cardinality. The findings also
      indicate that an understanding of cardinality emerges relatively suddenly,
      consistent with the discovery or construction of a principle. Whether nursery
      pupils treat counting simply as a conventional routine without cardinal
      significance appears to depend on the situation as well as on their understanding
      of cardinality. The findings are discussed in relation to Karmiloff-Smith's
      Representational Redescription model.

PMID- 9008427
TI  - The modulatory effect of aminothiols on the clastogenic activity of X-rays
      assayed by the vivo mouse micronucleus test.
AB  - The modulatory effect of AET (S-2-aminoethylisothio-uronium bromide hydrobromide)
      and WR-2721 (S-2-/3-ami-nopropylamino/ethylphosphorothioic acid) on the
      clastogenic activity of X-rays was assessed by the in vivo mouse micronucleus
      test. The frequency of micronucleated polychromatic erythrocytes (MNPCEs) in the
      peripheral blood of adult male Swiss mice exposed to 5 Gy X-rays alone, or
      treated with AET or WR-2721, at a does of 200 mg/kg body weight, 15 or 30 minutes
      prior to X-irradiation, respectively, was determined during a fifteen-day period.
      The number of micronuclei increased on day 1 post-irradiation in X-irradiated
      mice and declined thereafter with the frequency of MNPCEs remaining lower in the
      thiol pre-treated mice. A more effective protection against the clastogenic
      activity of X-rays in the erythropoietic system was observed after WR-2721
      administration than AET application.

PMID- 9008429
TI  - Changes in human blood pressure with season, age and solar cycles: a 26 year
      record.
AB  - The record was studied of a 71-year-old, diurnally active (0700-2200 hours) male
      psychiatrist (G.N.) who self-measured systolic and diastolic blood pressure (BPS
      and BPD) mostly but not exclusively on Sunday mornings, from 1969 to 1994. A
      large about-yearly change was revealed which increased with age and was
      accompanied by a decreasing trend in the yearly rhythm-adjusted mean (MESOR; P <
      0.01). According to conventional criteria that specify only upper limits of
      acceptability, G.N. was hypertensive in summer and normotensive in other seasons.
      Since changes in both MESOR and circannual amplitude occurred, a systematic
      surveillance of BP is the chronobiological recommendation.

PMID- 9008430
TI  - Changes in cold tolerance due to a 14-day stay in the Canadian Arctic.
AB  - Response to cold exposure tests both locally and of the whole body were examined
      in subjects who stayed in the arctic (average maximum and minimum temperatures 
      11 and -21 degrees C respectively) for 14 days of skiing and sleeping in tents.
      These changes were compared to responses in subjects living working in Ottawa,
      Canada (average max. and min. temperatures -5 and -11 degrees C respectively).
      The tests were done before the stay in the Arctic (Pre), immediately after the
      return (Post 1) and approximately 32 days after the return (Post 2). For the
      whole-body cold exposure each subject, wearing only shorts and lying on a rope
      mesh cot, was exposed to an ambient temperature of 10 degrees C. There was no
      consistent response in the changes of metabolic or body temperature to this
      exposure in either of groups and, in addition, the changes over time were
      variable. Cold induced vasodilatation (CIVD) was determined by measuring
      temperature changes in the middle finger of the nondominant hand upon immersion
      in ice water for 30 min. CIVD was depressed after the Arctic exposure whilst
      during the Post 2 testing, although variable, did not return to the Pre values;
      the responses of the control group were similar. These results indicate that
      normal seasonal changes may be as important in adaptation as a stay in the
      Arctic. Caution is advised in the separation of seasonal effects when examining
      the changes in adaptation after exposure to a cold environment.

PMID- 9008428
TI  - Clinical relevance of about-yearly changes in blood pressure and the environment.
AB  - Changes identified by inferential statistics from summer to winter of high to low
      arterial blood pressures (BP) have been quantified as a large predictable about
      yearly BP swing. This condition of a large annual BP amplitude (LABPA) raises
      concern about hypotension as well as hypertension and raises new questions
      regarding appropriate guidelines for diagnosis and treatment. Recommendations
      made in the fall on the basis of data collected in the summer may be totally
      inadequate in dealing with the patient's condition in the winter. In order to
      avoid such mistakes, it is imperative to implement a systematic surveillance of
      BP in the light of current chronobiological limits. Patients with a large
      circannual BP amplitude are particularly suited for a study of the underlying
      hormonal mechanisms. The longitudinal monitoring of their BP is also amenable to
      the study of environmental influences from near and far.

PMID- 9008431
TI  - Enhanced thermogenesis in rats by Panax ginseng, multivitamins and minerals.
AB  - Substances which enhance endurance for physical and mental work and increase non
      specific resistance to stress during a prolonged stay in physiologically adverse
      habitats are called 'adaptogens'. Panax ginseng is well known for its anti-stress
      and adaptogenic properties. In the present study, adaptogenic activity by the
      intake of a herbo-vitamin-mineral preparation (HVMP) containing P. ginseng and
      multivitamin-mineral preparation (MVMP) was evaluated using the cold-hypoxia
      restrained (C-H-R) animal model. The aim was to determine whether the cold
      tolerance and recovery from acute hypothermia mediated by P. ginseng was modified
      by simultaneous intake of additional vitamins and minerals. Results suggest that
      the adaptogenic effect of HVMP was more or less the sum total of its two
      components P. ginseng and MVMP. In HVMP, P. ginseng was found to be effective for
      developing resistance to cooling and MVMP helped in stimulating faster recovery
      from acute hypothermia.

PMID- 9008432
TI  - The importance of air quality in human biometeorology.
AB  - Often we encounter a misunderstanding based on the assertion that the criterion
      of air quality is excluded from studies into meteorology and climatology. In
      contrast to this, it must be stressed that the admixtures and pollutants
      pertaining to air quality criteria belong to the atmosphere and therefore, of
      course, to the field of meteorology, and due to their possible effects also to
      human biometeorology. A normal weather forecast should include data concerning
      the concentrations of ozone, nitrogen dioxide, and other substances.
      Biometeorological weather classifications should also include mention of air
      quality rather more than previously. For instance, the classification after
      Bucher used in Germany is referred to and supplemented with respect to air
      quality. Analogous relationships hold true for the global classification of
      climates. As an example, the well-known classification after Koeppen is
      supplemented according to air quality.

PMID- 9008433
TI  - Effect of enhanced geomagnetic activity on hypothermia and mortality in rats.
AB  - The hypothesis was investigated that variability in the severity of limbic
      seizure-induced hypothermia in rats was affected by ambient geomagnetic activity.
      Data were obtained in support of this hypothesis. The depth of the hypothermia
      was significantly (P < 0.001) reduced if the ambient geomagnetic activity
      exceeded 35 nT to 40 nT. Mortality during the subsequent 5 days was increased
      when the geomagnetic activity was > 20 nT. The magnitude of the effect was
      comparable to the difference between exposure to light or to darkness during the
      20 h after the induction of limbic seizures.

PMID- 9008434
TI  - Lipoprotein(a), a clinically elusive lipoprotein particle.

PMID- 9008435
TI  - Lipid hypothesis of cardiovascular calcification.

PMID- 9008436
TI  - Is noninvasive testing for coronary artery disease accurate?

PMID- 9008437
TI  - Elective stenting of extracranial carotid arteries.

PMID- 9008438
TI  - Clinical reality of lowering total and LDL cholesterol.

PMID- 9008439
TI  - Intravascular stent endothelialization. A goal worth pursuing?

PMID- 9008440
TI  - Arginine: a new therapy for atherosclerosis?

PMID- 9008441
TI  - Glucose metabolism in the ischemic heart.

PMID- 9008442
TI  - Sympathetic alternans. Evidence for arterial baroreflex control of muscle
      sympathetic nerve activity in congestive heart failure.
AB  - Alternation in the amplitude of muscle sympathetic nerve activity (MSNA) was
      documented in three patients with severe heart failure. In the index patient with
      pulsus alternans, the amplitude of MSNA was inversely related to changes in the
      preceding diastolic pressure with a lag time of 1.2 to 1.3 seconds, indicating
      that oscillations in burst amplitude are determined primarily by changes in this
      component of blood pressure. Spectral analysis of the blood pressure and MSNA
      signals identified two spectral peaks, one at the cardiac frequency and a second
      peak, with greater spectral power, at the alternans frequency (ie, at half the
      heart rate). The latter peak for both blood pressure and MSNA disappeared when
      alternans was abolished by nitroglycerin. The presence of sympathetic alternans
      in synchrony with pulsus alternans and the rapid transduction of changes in the
      diastolic blood pressure afferent signal to the amplitude of sympathetic outflow
      indicate that the arterial baroreflex control of MSNA must be active and rapidly
      responsive in human heart failure.

PMID- 9008443
TI  - Apoptosis in human acute myocardial infarction.
AB  - BACKGROUND: After reopening of the infarct-related coronary artery,
      cardiomyocytes continue to die during reperfusion. The mechanisms of cell death
      have been subject to debate. We studied whether an apoptotic type of cell death
      occurs in human acute myocardial infarction (AMI). METHODS AND RESULTS: We
      studied myocardial samples of eight patients who died of AMI and had patent
      infarct-related arteries at autopsy. Six of the patients had received initially
      successful thrombolysis. Extensive formation of DNA strand breaks, the typical
      biochemical feature of apoptosis, was detected with the use of the in situ DNA
      end-labeling method. Apoptotic cardiomyocytes were observed particularly in the
      border zones of histologically infarcted myocardium, whereas very few apoptotic
      cells were present in the remote noninfarcted myocardium. Internucleosomal
      fragmentation was confirmed by agarose gel electrophoresis of DNA isolated from
      the representative myocardial areas. CONCLUSIONS: This study provides evidence
      that in addition to overt necrosis, a subset of myocytes undergo apoptosis during
      ischemia-reperfusion injury. Apoptosis may provide a new target for
      cardioprotection during evolving AMI in humans.

PMID- 9008444
TI  - Effect of cholesterol reduction on myocardial ischemia in patients with coronary
      disease.
AB  - BACKGROUND: Cholesterol lowering is associated with a reduction in cardiovascular
      morbidity and mortality. This study sought to determine whether cholesterol
      lowering also results in a reduction of myocardial ischemia during daily life.
      METHODS AND RESULTS: We enrolled 40 patients with proven coronary artery disease,
      total serum cholesterol between 191 and 327 mg/dL, and at least one episode of ST
      segment depression on ambulatory ECG monitoring. Twenty patients were randomized
      to an American Heart Association Step 1 diet plus placebo (placebo group) and 20
      to the same diet plus lovastatin (treatment group). Serum cholesterol and LDL
      cholesterol levels and ambulatory monitoring were repeated after 4 to 6 months of
      therapy. The two groups were comparable with respect to baseline characteristics,
      number of episodes of ST-segment depression, and baseline serum cholesterol
      levels. The treatment group had lower mean total and LDL cholesterol levels at
      study end and experienced a significant reduction in the number of episodes of ST
      segment depression compared with the placebo group. ST-segment depression was
      completely resolved in 13 of 20 patients (65%) in the treatment group versus 2 of
      20 (10%) in the placebo group. The treatment group exhibited a highly significant
      reduction in ischemia (P < .001). By logistic regression, treatment with diet and
      lovastatin was an independent predictor of ischemia resolution. CONCLUSIONS:
      Cholesterol lowering with lovastatin appears to be effective in eliminating
      myocardial ischemia during daily life in a significant proportion of patients.

PMID- 9008445
TI  - Lipoprotein(a) as a determinant of coronary heart disease in young women.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] appears to be a risk factor for coronary heart
      disease (CHD) in men. The role of Lp(a) in women, however, is less clear. METHODS
      AND RESULTS: We examined the ability of Lp(a) to predict CHD in a population
      based case-control study of women 65 years of age or younger who lived in the
      greater Stockholm area. Subjects were all patients hospitalized for an acute CHD
      event between February 1991 and February 1994. Control subjects were randomly
      selected from the city census and were matched to patients by age and catchment
      area. Lp(a) was measured 3 months after hospitalization by use of an
      immunoturbidometric method (Incstar) calibrated to the Northwest Lipid Research
      Laboratories (coefficient of variation was < 9%). Of the 292 consecutive
      patients, 110 (37%) were hospitalized for an acute myocardial infarction, and 182
      were hospitalized (63%) for angina pectoris. The mean age for both patients and
      control subjects was 56 +/- 7 years. Of participants, 74 patients (25%) and 84
      control subjects (29%) were premenopausal. The distributions of Lp(a) were highly
      skewed in both patients and control subjects, with a range from 0.001 to 1.14
      g/L. Age-adjusted odds ratio for CHD in the highest versus the lowest quartile of
      Lp(a) was 2.3 (95% confidence interval [CI], 1.4 to 3.7). After adjustment for
      age, smoking, education, body mass index, systolic blood pressure, total
      cholesterol, triglycerides, and HDL, the odds ratio was 2.9 (95% CI, 1.6 to 5.0).
      The odds ratios were similar when myocardial infarction and angina patients were
      compared with their respective control subjects. The odds ratios were 5.1 (95%
      CI, 1.4 to 18.4) and 2.4 (95% CI, 1.3 to 4.5) in premenopausal and postmenopausal
      women, respectively. CONCLUSIONS: These results suggest that Lp(a) is a
      determinant of CHD in both premenopausal and postmenopausal women.

PMID- 9008446
TI  - Leisure-time physical activity but not work-related physical activity is
      associated with decreased plasma viscosity. Results from a large population
      sample.
AB  - BACKGROUND: Regular leisure-time physical activity (LTPA) is inversely associated
      with coronary heart disease (CHD). This has been mainly explained by its impact
      on traditional CHD risk factors, but more recently it was also shown to lower
      fibrinogen, which largely determines plasma viscosity. No data on the effect of
      work activity (WA) on plasma viscosity have been published. METHODS AND RESULTS:
      We studied the relationship between self-reported LTPA or WA and plasma viscosity
      as well as other CHD risk factors in 3522 men and women age 25 to 64 years.
      Physical activity was assessed by questionnaire. LTPA was inversely associated
      with plasma viscosity in both sexes. The unadjusted mean differences in plasma
      viscosity in men between no activity and the highest activity were 0.024 mPa.s
      (95% confidence interval [CI], 0.016 to 0.032 mPa.s, P < .001) during winter and
      0.024 mPa.s (95% CI, 0.016 to 0.031 mPa.s, P < .001) during summer. After
      adjustment for age, cholesterol, smoking, blood pressure, body mass index, and
      years of education, mean differences decreased but still remained substantial and
      statistically significant (0.010 mPa.s; 95% CI, 0.003 to 0.018 mPa.s [P = .009]
      for winter activity; and 0.010 mPa.s; 95% CI, 0.002 to 0.017 mPa.s [P = .011] for
      summer activity). Similar results were found in women. WA showed no appreciable
      association with plasma viscosity after controlling for the covariates.
      CONCLUSIONS: LTPA is inversely associated with plasma viscosity, independent of
      other risk factors, whereas WA shows no material effect in men and women.
      Decreased plasma viscosity may represent one mechanism through which LTPA confers
      a decrease of CHD risk.

PMID- 9008447
TI  - Improved outcome of elderly patients (> or = 75 years of age) with acute
      myocardial infarction from 1981-1983 to 1992-1994 in Israel. The SPRINT and
      Thrombolytic Survey Groups. Secondary Prevention Reinfarction Israel Nifedipine
      Trial.
AB  - BACKGROUND: The number of elderly patients experiencing acute myocardial
      infarction (AMI) is growing rapidly, and their hospital mortality rate remains
      high, although mortality after AMI declined in the 1990s with the introduction of
      new therapeutic modalities. METHODS AND RESULTS: We compared the management, in
      hospital complications, and 30-day and 1-year mortality rates in two cohorts of
      elderly (> or = 75 years of age) AMI patients in the coronary care units in
      Israel before and after the reperfusion era. The first cohort of 789 consecutive
      patients was from the Secondary Prevention Reinfarction Israel Nifedipine Trial
      registry in 1981-1983; the second 366 patients came from two prospective
      nationwide surveys in 1992 and 1994. Reperfusion therapies were not used in 1981
      1983 but were used in 1992-1994. The 30-day mortality rate declined from 38% in
      1981-1983 to 27% in 1992-1994 (odds ratio, 0.49; 95% confidence interval [CI],
      0.34 to 0.71), and the cumulative 1-year mortality rate declined from 52% to 38%
      (hazard ratio [HR], 0.62; 95% CI, 0.50 to 0.76). In the 1992-1994 cohort, the
      decline in mortality was most marked in patients reperfused by thrombolysis
      and/or percutaneous transluminal coronary angioplasty or coronary artery bypass
      graft surgery but was also evident in nonreperfused patients: cumulative 1-year
      mortality rate was 29% in the former (HR, 0.45; 95% CI, 0.31 to 0.67) and 42% in
      the latter (HR, 0.60; 95% CI, 0.46 to 0.78). CONCLUSIONS: During the last decade,
      elderly (> or = 75 years) AMI patients experienced fewer in-hospital
      complications and lower 30-day and 1-year mortality rates, which declined
      approximately 30%, most markedly in reperfused patients. The favorable outcome in
      1992-1994 was related to changes in patient management. Reperfusion therapy is
      therefore also advocated in elderly AMI patients, unless specific
      contraindications are present.

PMID- 9008448
TI  - TNK-tissue plasminogen activator in acute myocardial infarction. Results of the
      Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial.
AB  - BACKGROUND: TNK-tissue plasminogen activator (TNK-TPA) is a genetically
      engineered variant of TPA, which in experimental models has a slower plasma
      clearance and greater fibrin specificity and is 80-fold more resistant to
      plasminogen activator inhibitor-1 than alteplase TPA. METHODS AND RESULTS: The
      thrombolysis in Myocardial Infarction (TIMI) 10A trial was a Phase 1, dose
      ranging pilot trial designed to evaluate the pharmacokinetics, safety, and
      efficacy of TNK-TPA in patients with acute myocardial infarction. One hundred
      thirteen patients with acute ST-segment elevation myocardial infarction
      presenting within 12 hours and without contraindications to thrombolysis were
      enrolled and treated with a single bolus of TNK-TPA over 5 to 10 seconds with
      doses ranging from 5 to 50 mg. TNK-TPA demonstrated a plasma clearance of 151 +/-
      55 mL/min and a half-life of 17 +/- 7 minutes. Comparable values for wild-type
      TPA are 572 +/- 132 mL/min and 3.5 +/- 1.4 minutes, respectively. Systemic
      fibrinogen and plasminogen levels fell by only 3% and 13%, respectively, at 1
      hour after TNK-TPA administration. TIMI grade 3 flow at 90 minutes was achieved
      in 57% to 64% of patients at the 30- to 50-mg doses. Seven patients (6.2%)
      experienced a major hemorrhage, which occurred at a vascular access site in six
      patients. CONCLUSIONS: TNK-TPA has a prolonged half-life so it can be
      administered as a single bolus. TNK-TPA appears to be very fibrin specific, and
      the initial patency and safety profiles are encouraging. Further study of this
      new thrombolytic agent is ongoing.

PMID- 9008449
TI  - Mechanical pressure and stretch release endothelin-1 from human atherosclerotic
      coronary arteries in vivo.
AB  - BACKGROUND: Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with
      mitogenic properties. In vitro, vascular release of ET-1 is increased in response
      to mechanical stress. The goal of the present study was to examine whether ET-1
      is released from human atherosclerotic coronary arteries in vivo in response to
      mechanical pressure and stretch and to characterize immunoreactivity for ET-1 and
      its precursor, big ET-1, within the atheromatous plaque. METHODS AND RESULTS:
      Circulating ET-1 levels were measured in 20 patients before and after coronary
      angioplasty for stable angina at three sampling sites: the femoral artery and the
      coronary artery segments proximal and distal to the lesion dilated. In addition,
      atheromatous tissue obtained from 20 patients undergoing directional coronary
      atherectomy for stable angina were analyzed for immunoreactivity for ET-1 and big
      ET-1. In patients undergoing angioplasty, ET-1 levels in the distal coronary
      artery increased after balloon dilatation (8.4 +/- 0.9 to 16.4 +/- 2 pg/mL, P <
      .05); proximal coronary artery and systemic ET-1 levels were unchanged. The
      degree of mechanical stress applied (product of duration and pressure of balloon
      inflation) correlated with the change in distal coronary artery ET-1 levels (r =
      .71, P < .01). Immunoreactivity for big ET-1 and ET-1 was ubiquitous in the
      extracellular space and the intracellular compartment (macrophages, myointimal
      cells, myofibroblasts, and endothelial cells) of human coronary atheromatous
      tissue. CONCLUSIONS: Big ET-1 and ET-1 immunoreactivity is ubiquitous within the
      intracellular and extracellular compartments of coronary atherosclerotic tissue.
      ET-1 is released from these sites in response to mechanical stress. These
      findings support a role for endothelins in the evolution and progression of
      coronary atherosclerosis in humans.

PMID- 9008450
TI  - Serial follow-up after optimized ultrasound-guided deployment of Palmaz-Schatz
      stents. In-stent neointimal proliferation without significant reference segment
      response.
AB  - BACKGROUND: The effects of ultrasound-guided high-pressure stenting on late stent
      and reference segment dimensions are unknown. In this study, we report about
      angiographic and ultrasound measurements to assess the amount and distribution of
      neointimal ingrowth within the stent and the changes of plaque burden and
      dimensions within the reference segments. METHODS AND RESULTS: Sixty-eight
      consecutive patients with 72 lesions received single or multiple Palmaz-Schatz
      coronary stents with a standardized protocol for stent optimization under
      ultrasound guidance. The residual angiographic diameter stenosis was 3 +/- 12%
      (reference diameter, 3.16 +/- 0.61 mm). At follow-up 4.8 +/- 2.5 months later,
      angiography revealed a diameter stenosis of 27 +/- 21% with a restenosis rate of
      15.3% (confidence interval: 7.8% to 25.6%). Lumen renarrowing within the stent
      was exclusively due to neointimal ingrowth; no stent compression was observed.
      The neointima covered 20 +/- 20% of the stent area and was more pronounced in the
      midportion of the stent. Volumetric assessment performed in 26 patients resulted
      in 13 +/- 14% or 65 +/- 28% of the stent volume occupied by neointimal ingrowth
      in patients without or with restenosis, respectively. Vessel remodeling had an
      impact on lumen dimensions only at reference sites but not within the stent.
      Plaque burden of 46 +/- 11% and 48 +/- 11% at the proximal and distal reference
      sites, respectively, did not show a relevant progression during the follow-up.
      CONCLUSIONS: Serial ultrasound analyses did not show any evidence of stent
      compression or relevant vessel remodeling. Restenosis was solely due to
      neointimal ingrowth. Despite a considerable plaque burden within the reference
      segments, there was no relevant progression of the disease adjacent to the stent.

PMID- 9008451
TI  - Transmyocardial laser revascularization. Histological features in human
      nonresponder myocardium.
AB  - BACKGROUND: The creation of transmyocardial channels from the epicardium to the
      left ventricular cavity with the use of a CO2 laser is a modern approach in the
      treatment of patients with chronic ischemic cardiac disease. The histological
      features of human myocardium at different times after transmyocardial laser
      therapy have not been previously described. We had the opportunity to examine
      hearts from patients who died without clinical evidence of a persistent
      therapeutic effect at 3, 16, and 150 days after transmyocardial laser
      revascularization (TMR) respectively. METHODS AND RESULTS: We grossly localized
      the laser-created channels in unfixed and formalin-fixed tissue. Three
      ventricular levels were defined for cutting the hearts into four segments. Then,
      transmural blocks were excised and cut crosswise and lengthwise for histological
      investigation through the use of established staining methods. On day 3, laser
      induced channels were filled with abundant granulocytes and thrombocytes,
      fibrinous network, and detritus and were surrounded by severe myocardial
      necrosis. Furthermore, the epicardial and endocardial portions were obstructed by
      fibrinous network and microclots. Granulocytes were mostly absent on day 16; in
      addition, the channels were filled with erythrocytes or fibrinous network. On day
      150, we observed a string of cicatricial tissue admixed with a polymorphous blood
      filled capillary network and small veins, which very rarely had a continuous
      wrinkled link to the left ventricular cavity. CONCLUSIONS: We found different
      stages of wound healing in human nonresponder myocardium after TMR, resulting in
      scarred tissue that displayed capillary network and dilated venules without
      evidence of patent and endothelialized laser-created channels. Experimental
      studies are necessary to analyze the morphological basis for TMR-mediated effects
      in human responder myocardium.

PMID- 9008452
TI  - Elective stenting of the extracranial carotid arteries.
AB  - BACKGROUND: Surgical endarterectomy has been shown to be superior to medical
      management in the management of severe carotid stenosis in both symptomatic and
      asymptomatic patients. Endarterectomy, although effective, does have limitations,
      and percutaneous techniques may offer an alternative method of treatment. METHODS
      AND RESULTS: The feasibility and safety of percutaneous carotid angioplasty and
      elective (primary) stenting was evaluated prospectively in a consecutive series
      of 107 patients. One hundred twenty-six carotid arteries with significant
      stenosis were treated. This series represented a high-risk subset that included
      patients with previous ipsilateral endarterectomy and severe medical comorbidity.
      Forty-five percent of the patients were referred by surgeons. Patients had
      independent neurological examinations before and after the procedure and follow
      up cerebral angiography at 6 months. The mean (+/- SD) stenosis was reduced from
      78 +/- 14% to 2 +/- 5%. There were 7 minor strokes, 2 major strokes, and 1 death
      during the initial hospitalization and first 30 days after the procedure. For the
      combined end point of all strokes and death, the incidence was 7.9%. For
      ipsilateral major stroke and death, the incidence was 1.6%. There were no strokes
      during the follow-up period. Mean angiographic stenosis at 6 months in 81
      patients was 18 +/- 16% (range, -21% to 57%). Four (4.9%) of these 81 patients
      had asymptomatic restenosis. Five asymptomatic patients had repeat intervention:
      2 had angioplasty for restenosis, 2 had angioplasty for stent deformation, and 1
      had endarterectomy for restenosis. CONCLUSIONS: In a high-risk group of patients,
      percutaneous carotid angioplasty and stenting are feasible and can be performed
      with low restenosis and repeat intervention rates.

PMID- 9008453
TI  - Actuarial outcome after catheter balloon commissurotomy in patients with mitral
      stenosis.
AB  - BACKGROUND: The goal of the present study was to determine the intermediate-term
      survival and the independent predictors of survival and event-free survival for
      patients who undergo catheter balloon commissurotomy (CBC). METHODS AND RESULTS:
      CBC for the treatment of mitral stenosis was performed in 132 patients from 1986
      through 1994. The use of CBC increased the mitral valve area (MVA) from 1.0 +/-
      0.3 to 1.9 +/- 0.6 cm2 (P < .001). There were six early deaths (4.5%) up to 1
      month after CBC ("hospital" deaths). In the past 4.5 years, there have been no
      hospital deaths. Four late deaths occurred after elective mitral valve
      replacement (MVR). Actuarial 7-year survival was 95 +/- 1%; when mortality after
      MVR is included, 7-year survival was 83 +/- 6%. Actuarial 1-, 3-, 5-, and 7-year
      event-free survival (survival without MVR or repeat CBC) was 80 +/- 4%, 77 +/-
      4%, 65 +/- 6%, and 65 +/- 6%. On multivariate analysis, the only two independent
      predictors (both after CBC) of 7-year event-free survival were MVA of > or = 1.5
      versus < 1.5 cm2 (75 +/- 7% versus 32 +/- 12%) and mean pulmonary artery wedge
      pressure of < or = 18 versus > 18 mm Hg (84 +/- 6% versus 38 +/- 11%) (P < .001
      for both). Patients with MVA of > or = 1.5 cm2 (n = 96) could be further
      subdivided into high- and low-risk subgroups for 7-year event-free survival by
      two post-CBC variables: mean pulmonary artery wedge pressure of < or = 18 versus
      > 18 mm Hg (90 +/- 6% versus 48 +/- 14%) (P = .0002) and cardiac index of > or =
      2.5 versus < 2.5 L.min-1.m-2 (82 +/- 8% versus 61 +/- 13%) (P = .004). Patients
      with post-CBC MVA of < 1.5 cm2 (n = 24) had no additional predictors of event
      free survival. Of patients who did not undergo MVR or repeat CBC, 8% were in New
      York Heart Association functional class III and 92% were in class I or early
      class II at the last follow-up. CONCLUSIONS: The rates for intermediate-term
      survival and event-free survival after CBC are very encouraging. Most patients
      without events were asymptomatic or minimally symptomatic. Thus, in selected
      patients with mitral stenosis who require an interventional procedure, CBC is the
      procedure of choice at centers with physicians who have experience and skill in
      performing this procedure.

PMID- 9008454
TI  - Prediction of outcome of patients with life-threatening ventricular arrhythmias
      treated with automatic implantable cardioverter-defibrillators using SPECT
      perfusion imaging.
AB  - BACKGROUND: In the present study, we examined the predictors of outcome of 103
      patients with coronary artery disease and left ventricular dysfunction who had
      life-threatening ventricular arrhythmias and were treated with implantable
      cardioverter-defibrillators with the use of single-photon emission computed
      tomography (SPECT). METHODS AND RESULTS: During a mean follow-up of 29 months,
      there were 29 cardiac deaths. In comparison with patients who died, survivors had
      less diabetes mellitus (45% versus 19%, P < .007), higher left ventricular
      ejection fraction (23 +/- 9% versus 27 +/- 11%, P = .04), and fewer perfusion
      defects as determined with stress SPECT (15 +/- 5 versus 12 +/- 5, P < .004).
      Most of the perfusion defects were fixed, indicative of scarring; the extent of
      reversible defects did not differ (2 +/- 3 in survivors and 3 +/- 4 in
      nonsurvivors). Multivariate Cox survival analysis identified the number of fixed
      defects as the only independent predictor of death (chi 2 = 10, P = .002). There
      were six deaths among 42 patients (14%) with < 8 fixed defects compared with 23
      deaths among 61 patients (38%) with > or = 8 defects (P = .005). The 4-year
      survival was better in patients with < 8 segmental fixed defects than in those
      with > or = 8 fixed defects (80% versus 36%) (chi 2 = 8, P = .005). CONCLUSIONS:
      The myocardial perfusion pattern is an important determinant of outcome in
      patients with life-threatening ventricular arrhythmias who are treated with a
      implantable cardioverter-defibrillator. The extent of scarring separates patients
      into high- and low-risk groups with a 2.7-fold difference in death rate.

PMID- 9008455
TI  - Baroreflex sensitivity in patients with vasovagal syncope.
AB  - BACKGROUND: In the present study, we tested the hypothesis that baroreflex
      sensitivity is reduced in patients with vasovagal syncope compared with normal
      control subjects. METHODS AND RESULTS: We investigated 30 patients with vasovagal
      syncope (mean age, 43.6 +/- 16.7 years; 14 men and 16 women) and 32 normal
      control subjects (mean age, 41.8 +/- 17.0 years; 24 men and 8 women).
      Cardiopulmonary baroreceptor sensitivity was assessed by measuring the change in
      forearm vascular resistance during subhypotensive lower body negative pressure
      (LBNP). Carotid baroreflex sensitivity was assessed by measuring the change in RR
      interval during the manipulation of carotid transmural pressure. Phenylephrine
      baroreceptor sensitivity was assessed on the basis of the linear regression slope
      of the RR interval versus systolic blood pressure during the increment in blood
      pressure after intravenous administration of phenylephrine. In patients with
      vasovagal syncope, during the application of -10 mm Hg LBNP, forearm vascular
      resistance decreased by 0.7 +/- 11.6 U versus an increase of 8.3 +/- 6.2 U in
      control subjects (P = .002). Phenylephrine baroreceptor sensitivity was 11 +/- 7
      ms/mm Hg in patients versus 14 +/- 6 ms/mm Hg in control subjects (P = NS).
      Carotid baroreflex sensitivity was 4 +/- 6 versus 4 +/- 2 ms/mm Hg in patients
      and control subjects, respectively (P = NS). CONCLUSIONS: In patients with
      vasovagal syncope, during the application of subhypotensive LBNP, there is
      impaired forearm vasoconstriction or paradoxical forearm vasodilation. This
      suggests impaired cardiopulmonary baroreceptor inactivation or paradoxical
      activation of these receptors and is consistent with reduced cardiopulmonary
      baroreceptor sensitivity.

PMID- 9008456
TI  - Depolarization-repolarization inhomogeneity after repair of tetralogy of Fallot.
      The substrate for malignant ventricular tachycardia?
AB  - BACKGROUND: We have previously shown that QRS prolongation (> or = 180 ms) is a
      risk marker for sustained ventricular tachycardia (VT) late after repair of
      tetralogy of Fallot (rTOF). We have now examined the dispersion of QT and its
      components QRS and JT, in an attempt to determine whether any association exists
      between these measurements and the presence of VT in these patients. METHODS AND
      RESULTS: QRS duration and QT/QRS/JT dispersion were measured manually from
      standard ECGs in 10 syncopal rTOF patients (21.4 +/- 4.6 years after repair;
      group 1) with QRS > or = 180 ms and with documented VT and were compared with 9
      rTOF patients with QRS > or = 180 ms and no VT (group 2), 40 rTOF patients with
      QRS < 180 ms and no clinical arrhythmias (group 3), and 40 nontetralogy control
      subjects (20 with right bundle-branch block [group 4] and 20 with normal ECG
      patterns [group 5]). Mean QT dispersion (62 +/- 36 ms) in the tetralogy patients
      was greater than in the nontetralogy control subjects (34 +/- 10 ms, P < .001).
      There were significant differences in all measured parameters between groups 1
      and 3 and more importantly between groups 1 and 2. QRS dispersion in group 1 also
      correlated with QRS duration but not with JT dispersion. CONCLUSIONS: Our data
      suggest that both depolarization and repolarization abnormalities are associated
      with VT after rTOF. Furthermore, increased QT, QRS, and JT dispersions, combined
      with a QRS > or = 180 ms, refine risk stratification for VT in these patients.

PMID- 9008457
TI  - Sex and test verification bias. Impact on the diagnostic value of exercise
      echocardiography.
AB  - BACKGROUND: The use of exercise echocardiography for the diagnosis of coronary
      artery disease (CAD) has been validated in pilot studies but is not documented in
      clinical practice and in women comparatively with men. The objectives of this
      study were to determine the effects of sex and of test verification bias on the
      diagnostic performance of exercise echocardiography. METHODS AND RESULTS: Three
      thousand six hundred seventy-nine consecutive patients (1714 women, 1965 men) who
      underwent an exercise echocardiographic study were studied; the observed
      sensitivity, specificity, and correct classification rate were calculated among
      340 patients (244 men, 96 women) who underwent angiography; to study the effect
      of test verification bias, sensitivity and specificity were estimated for all
      patients who underwent exercise echocardiography including those not referred to
      angiography. In the angiographic group, the prevalence of CAD was 60% in women
      and 80% in men. The observed sensitivity and specificity of exercise
      echocardiography was 78% and 44% in men and 79% and 37% in women. After
      adjustment for test verification bias, the estimated sensitivity was lower in
      women (32% versus 42% in men), whereas specificity was similar in both sexes. The
      positive predictive value was lower in women (66%) compared with men (84%).
      CONCLUSIONS: In clinical practice, test verification bias results in a lower
      observed specificity and a higher sensitivity of exercise echocardiography. In
      women, positive predictive value and adjusted sensitivity are lower compared with
      that in men.

PMID- 9008458
TI  - Effect of verapamil in intermittent claudication A randomized, double-blind,
      placebo-controlled, cross-over study after individual dose-response assessment.
AB  - BACKGROUND: The calcium antagonist verapamil is a vasodilator drug that has been
      shown to increase oxygen extraction of ischemic tissues in coronary and
      peripheral vascular disease. METHODS AND RESULTS: Since the balance between the
      positive and the negative effects of vasodilation may be delicate in ischemic
      diseases a dose-response study (dose range, 120 to 480 mg) was established to
      determine optimal, individual dosages of slow-release verapamil in 44 patients
      with stable intermittent claudication (Fontaine classification stage II) with
      respect to walking capacity. A randomized, double-blind, placebo-controlled,
      cross-over study (4 weeks) was performed to assess clinical and hemodynamic
      effects of verapamil. The optimal daily dose of verapamil on maximal walking
      ability was 120 (8 patients), 240 (8 patients), 360 (14 patients), and 480 mg (14
      patients). Walking distances were measured at a metronome-controlled speed of 60
      steps per minute on level surface. Optimal individual doses of verapamil
      increased mean pain-free walking distance by 29% from 44.9 to 57.8 meters (P <
      .01) and maximal walking distance by 49% from 100.7 to 149.8 meters (P < .001)
      compared with placebo. The increase in maximal walking distance correlated
      positively only with initial systolic ankle pressure (r = .49, P < .001) and
      ankle/brachial pressure index (r = .37, P < .013). Verapamil had no effect on
      systolic ankle pressure, ankle/brachial pressure index, peripheral leg
      temperature, or blood pressure, which suggests that the drug may have
      extrahemodynamic effects, possibly brought about through improved oxygen
      metabolism. CONCLUSIONS: Verapamil showed significant clinical benefits in
      patients with moderate intermittent claudication in this short-term study.
      Individual optimization of drug dosage should be considered an option both in
      trials and in the clinical setting in these patients.

PMID- 9008460
TI  - Physiological effects of adenoviral gene transfer of sarcoplasmic reticulum
      calcium ATPase in isolated rat myocytes.
AB  - BACKGROUND: In myocardial cells, relaxation is governed primarily by the
      sarcoplasmic reticulum (SR) Ca(2+)-ATPase transporting enzyme, which regulates
      Ca2+ sequestration into the SR. Human and experimental cardiomyopathies are
      associated with reduced SR Ca(2+)-ATPase activity. METHODS AND RESULTS: To modify
      intracellular calcium mobilization, we created a recombinant adenovirus designed
      to over-express the cardiac SR Ca(2+)-ATPase (SERCA2a) under the control of the
      Rous sarcoma virus (RSV). In neonatal rat myocytes, Ad.RSV.SERCA2a increased the
      expression of SERCA2a in a concentration-dependent and time-dependent fashion.
      Enhancement of SR Ca(2+)-ATPase activity was even greater than increases in
      SERCA2a protein content in cells infected with Ad.RSV.SERCA2a for 48 hours at a
      multiplicity of infection (MOI) from 0.1 to 10.0 pfu/cell. Intracellular calcium
      transients measured in the neonatal cells infected with Ad.RSV.SERCA2a were
      characterized by an abbreviation of the relaxation phase, an increase in peak
      [Ca2+]i release, and a decrease in resting [Ca2+]i levels. Ad.RSV.SERCA2a also
      enhanced the contraction of the myocardial cells as detected by shortening
      measurements. CONCLUSIONS: We found that adenovirus-mediated gene transfer of SR
      Ca(2+)-ATPase can modify intracellular calcium handling and shortening in
      myocardial cells. Such vectors should be useful in examining the role of reduced
      SERCA2a activity in the pathophysiology of heart failure and in developing
      strategies for gene therapy.

PMID- 9008459
TI  - Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1
      glucose transporters to the sarcolemma in vivo.
AB  - BACKGROUND: Myocardial ischemia increases heart glucose utilization in vivo.
      However, whether low-flow ischemia leads to the translocation of glucose
      transporter (GLUT)-4 and/or GLUT-1 to the sarcolemma in vivo is unknown. METHODS
      AND RESULTS: In a canine model, we evaluated myocardial glucose metabolism in
      vivo and the distribution of GLUT-4 and GLUT-1 by use of immunoblotting of
      sarcolemma and intracellular membranes and immunofluorescence localization with
      confocal microscopy. In vivo glucose extraction increased fivefold (P < .001) and
      was associated with net lactate release in the ischemic region. Ischemia led to
      an increase in the sarcolemma content of both GLUT-4 (15 +/- 2% to 30 +/- 3%, P <
      .02) and GLUT-1 (41 +/- 4% to 58 +/- 3%, P < .03) compared with the nonischemic
      region and to a parallel decrease in their intracellular contents.
      Immunofluorescence demonstrated the presence of both GLUT-4 and GLUT-1 on cardiac
      myocytes. GLUT-1 had a more prominent cell surface pattern than GLUT-4, which was
      primarily intracellular in the nonischemic region. However, significant GLUT-4
      surface labeling was found in the ischemic region. CONCLUSIONS: Translocation of
      the insulin-responsive GLUT-4 transporter from an intracellular storage pool to
      the sarcolemma occurs in vivo during acute low-flow ischemia. GLUT-1 is also
      present in an intracellular storage pool from which it undergoes translocation to
      the sarcolemma in response to ischemia. These results indicate that both GLUT-1
      and GLUT-4 are important in ischemia-mediated myocardial glucose uptake in vivo.

PMID- 9008461
TI  - L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL
      receptor knockout mice.
AB  - BACKGROUND: The potential antiatherosclerotic actions of NO were investigated in
      four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an
      animal model of familial hypercholesterolemia. Group 1 was fed a regular chow
      diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition,
      group 3 received supplemental L-arginine and group 4 received L-arginine and N
      omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS). METHODS AND
      RESULTS: Animals were killed at 6 months; aortas were stained with oil red O for
      planimetry and with antibodies against constitutive and inducible NOSs. Plasma
      cholesterol was markedly increased in the animals receiving the high-cholesterol
      diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not
      in those receiving L-arginine. Aortic atherosclerosis was present in all mice on
      the high-cholesterol diet. The mean atherosclerotic lesion area was reduced
      significantly (P < .01) in the cholesterol-fed mice given L-arginine compared
      with those receiving the high-cholesterol diet alone. The mean atherosclerotic
      lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving
      L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the
      atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell
      NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for
      inducible NOS and nitrotyrosine residues. CONCLUSIONS: The data indicate that L
      arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor
      knockout mice fed a high-cholesterol diet. The abrogation of the beneficial
      effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L
      arginine are mediated by NOS. The data suggest that L-arginine may be beneficial
      in familial hypercholesterolemia.

PMID- 9008462
TI  - Stent endothelialization. Time course, impact of local catheter delivery,
      feasibility of recombinant protein administration, and response to cytokine
      expedition.
AB  - BACKGROUND: Because prior studies have established the critical role of the
      endothelium in preventing vascular thrombosis and intimal thickening, we designed
      a series of experiments to determine the feasibility of percutaneous local
      catheter delivery of recombinant protein to accelerate development of an intact
      endothelial monolayer after stent implantation. METHODS AND RESULTS: Balloon
      injury followed by percutaneous delivery of a 15-mm-long, balloon-expandable
      metallic stent was performed in 64 rabbit external iliac arteries (baseline
      diameter, 2.67 +/- 0.07 mm). Planimetric time-course analysis disclosed < 20%
      stent endothelialization at 4 days, < 40% at 7 days, and near-complete
      endothelialization at 28 days. The reporter protein horseradish peroxidase and
      the endothelial cell-specific recombinant protein vascular endothelial growth
      factor (VEGF) were each effectively delivered from a local delivery catheter
      (channel balloon catheter, ChB) after stent implantation. Although local catheter
      delivery (of vehicle control) itself mildly retarded the extent of stent
      endothelialization (10.6 +/- 2.9%) versus no local delivery (25.5 +/- 6.6%, P =
      .045), local ChB delivery of 100 micrograms VEGF overcame this catheter effect:
      By day 7, stent endothelialization was nearly complete (91.8 +/- 3.8%) (P < .0001
      versus no local delivery). Consequently, stent thrombus was reduced in the VEGF
      treated group (mural thrombus, 5.3 +/- 3.7%) versus no local delivery (29.3 +/-
      6.8%, P = .006). Occlusive thrombus was seen only in the absence of local VEGF
      administration. CONCLUSIONS: (1) Local delivery of recombinant protein to the
      arterial wall is feasible after stent implantation, and (2) local delivery of the
      endothelial cell mitogen VEGF accelerates stent endothelialization, reducing
      stent thrombosis. These results thus establish a novel means by which the safety
      and/or bioactivity of endovascular stents may be further enhanced.

PMID- 9008463
TI  - Continuous subcutaneous angiopeptin treatment significantly reduces neointimal
      hyperplasia in a porcine coronary in-stent restenosis model.
AB  - BACKGROUND: In-stent restenosis results primarily from neointimal hyperplasia.
      This study evaluated the efficacy and the optimal mode of administration of
      angiopeptin, a somatostatin analogue with antiproliferative activity, in a
      porcine coronary in-stent restenosis model. METHODS AND RESULTS: Forty pigs were
      randomly assigned to one of four groups (n = 10 per group): (1) controls
      receiving saline infusion at the site of stent implantation via a local delivery
      catheter, (2) local treatment group receiving one-time treatment (200 (micrograms
      angiopeptin) at the site of stent placement, (3) systemic treatment group
      receiving continuous angiopeptin over a 1-week period via a subcutaneous osmotic
      pump (200 micrograms/kg total dose) and (4) combined local and systemic treatment
      group. Then, one oversized Palmaz-Schatz stent (mean ratio of stent to artery
      diameters, 1.3:1) was implanted in the left anterior descending coronary artery.
      The degree of neointimal reaction was evaluated 4 weeks later by angiography
      (maximal percent diameter stenosis), intravascular ultrasound (total in-stent
      neointimal volume), and histology (maximal area stenosis). Systemic treatment
      produced the least neointimal hyperplasia and significantly reduced in-stent
      restenosis compared with the control group by all end points, despite similar
      degrees of injury. Angiography showed 25 +/- 17% versus 50 +/- 17% diameter
      stenosis in the systemic angiopeptin group versus the control group (P < .0001),
      intravascular ultrasound revealed 23 +/- 10 versus 58 +/- 27 mm3 neointimal
      volume in the systemic angiopeptin versus control group (P = .0002), and
      histology showed 41 +/- 16% versus 69 +/- 18% area stenosis (P = .0016) in the
      systemic angiopeptin versus control group. Plasma angiopeptin levels revealed
      rapid clearance (within 6 hours) after local therapy, whereas the levels
      persisted for up to 2 weeks in the systemic group. CONCLUSIONS: This study shows
      that continuous subcutaneous treatment with angiopeptin after stent implantation
      significantly reduces in-stent restenosis by inhibiting neointimal hyperplasia.

PMID- 9008464
TI  - Recombinant staphylokinase variants with altered immunoreactivity. III: Species
      variability of antibody binding patterns.
AB  - BACKGROUND: The "charged cluster-to-alanine" substitution variants
      SakSTAR(K35A,E38A,K74A,E75A,R77A) and SakSTAR(K74A,E75A,R77A,E80A,D82A),
      previously identified as SakSTAR.M38 and SakSTAR.M89, respectively, induce less
      antibody formation in patients than wild-type recombinant staphylokinase
      (SakSTAR), but their specific activities are reduced by 50%. Therefore, the
      effect of the reversal of one or more of these substituted amino acids on the
      ratio of activity to antigenicity was studied. METHODS AND RESULTS: Fourteen
      mutants with one to four "alanine-to-wild-type" reversals were expressed in
      Escherichia coli and highly purified (> 95%). In rabbits immunized with wild-type
      SakSTAR, the combined K35,E38,K74,E75,R77 or K74,E75,R77,E80,E82 epitope
      accounted for only 30% of antibody absorption from plasma, and no clear
      immunodominant residue could be identified. In baboons immunized with SakSTAR,
      the K35,E38 and K74,E75,R77 epitopes or the K74,E75,R77 and E80,D82 epitopes
      contributed equally to account for 50% of total antibody binding, but no
      immunodominant residues were apparent. In pooled plasma from patients with
      peripheral arterial occlusion treated with wild-type SakSTAR, about 40% of the
      antibodies depended on K74 of epitope K74,E75,R77 for binding, whereas epitopes
      K35,E38 and E80,D82 had a negligible contribution toward antibody recognition.
      CONCLUSIONS: The recognition pattern by SakSTAR variants of antibodies induced
      with wild-type SakSTAR differs markedly among species. This implies that a
      systematic evaluation of reduced antigen recognition and antibody induction in
      humans will require the development of human or humanized systems. Surprisingly,
      SakSTAR(K74), with a single substitution of Lys74 with Ala, had an intact
      specific activity but did not absorb 40% of the antibodies induced in patients by
      treatment with wild-type SakSTAR.

PMID- 9008465
TI  - Recombinant staphylokinase variants with altered immunoreactivity. IV:
      Identification of variants with reduced antibody induction but intact potency.
AB  - BACKGROUND: The thrombolytic potency and antibody induction of selected variants
      of recombinant staphylokinase (SakSTAR), including SakSTAR(K74) with Lys74,
      SakSTAR(E75) with Glu75-, SakSTAR(EER) with Glu38, Glu75, and Arg77, and
      SakSTAR(K74ER) with Lys74, Glu75, and Arg77 replaced by Ala, were studied.
      METHODS AND RESULTS: In rabbits, SakSTAR(74) and SakSTAR(EER) elicited
      significantly less circulating neutralizing activity than SakSTAR and
      SakSTAR(E75) (P = .005 and P = .0002 versus SakSTAR, respectively). In baboons,
      SakSTAR(K74) induced significantly fewer antibodies than wild-type SakSTAR (P <
      .05). Intra-arterial administration in patients with peripheral arterial
      occlusion of SakSTAR(K74) (n = 11) or SakSTAR(K74ER) (n = 6) induced
      significantly fewer circulating neutralizing antibodies [median values and
      interquartile ranges, 20 (3.8 to 26) and 2.4 (0.2 to 59) micrograms compound
      neutralized/mL plasma after 3 to 4 weeks (P = .01 and P = .035 versus SakSTAR,
      respectively)] than SakSTAR (n = 9) [median value and interquartile range, 93 (24
      to 110) micrograms compound neutralized/mL plasma]. Overt neutralizing antibody
      induction (> 10 micrograms compound neutralized/mL plasma) occurred in all 9
      patients given wild-type SakSTAR, in 6 of the 11 SakSTAR(K74ER) patients (P =
      .038 versus SakSTAR), and in 2 of the 6 SakSTAR(K74ER) patients (P = .011 versus
      SakSTAR). CONCLUSIONS: SakSTAR(K74), a variant of recombinant staphylokinase with
      a single substitution of Lys74 with Ala, and SakSTAR(K74), with Lys74, Glu75, and
      Arg77 substituted with Ala, have intact thrombolytic potencies but induce
      significantly less antibody formation in patients.

PMID- 9008466
TI  - Upregulation of vascular angiotensin II receptor gene expression by low-density
      lipoprotein in vascular smooth muscle cells.
AB  - BACKGROUND: Because LDL and the angiotensin II type 1 (AT1) receptor are thought
      to be involved in the pathogenesis of chronic vascular disease, we studied
      possible interactions between these two biological systems in cultured rat
      vascular smooth muscle cells. METHODS AND RESULTS: Incubation of vascular smooth
      muscle cells with 100 micrograms/mL LDL profoundly increased AT1 receptor mRNA to
      approximately 250% of control levels as assessed by Northern hybridization
      analysis. This effect is maximal 12 hours after addition of LDL to the culture
      medium and is sustained for up to 24 hours. The LDL-induced upregulation is dose
      dependent, with a maximal effect obtained with 100 micrograms/mL LDL. There is a
      correlative increase of cell surface-associated AT1 receptors as assessed by
      saturation radioligand binding assays. The half-life of AT1 receptor mRNA is
      increased substantially by LDL compared with that of cells treated only with 5,6
      dichlorobenzimidazole to block transcription. Angiotensin II-induced elevation of
      cytosolic calcium concentration is significantly increased in vascular smooth
      muscle cells pretreated with LDL to 368 +/- 41 nmol/L compared with control cells
      pretreated with vehicle (248 +/- 33 nmol/L). Moreover, angiotensin II-induced DNA
      synthesis is markedly enhanced when cells are coincubated with 100 micrograms/mL
      LDL. CONCLUSIONS: These data reveal a significant upregulation of AT1 receptor
      gene expression by LDL in vascular smooth muscle cells through mechanisms that
      involve posttranscriptional mRNA stabilization. Ultimately, this AT1 receptor
      upregulation leads to an elevated functional response of vascular smooth muscle
      cells on angiotensin II stimulation.

PMID- 9008467
TI  - Prevention of bioprosthetic heart valve calcification by ethanol preincubation.
      Efficacy and mechanisms.
AB  - BACKGROUND: Calcification of the cusps of bioprosthetic heart valves fabricated
      from either glutaraldehyde cross-linked porcine aortic valves or bovine
      pericardium frequently causes the clinical failure of these devices. Our
      investigations studied ethanol pretreatment of glutaraldehyde cross-linked
      porcine aortic valves as a new approach to prevent cuspal calcification. The
      hypothesis governing this approach holds that ethanol pretreatment inhibits
      calcification resulting from protein structural alterations and lipid extraction.
      METHODS AND RESULTS: Results demonstrated complete inhibition of calcification of
      glutaraldehyde-pretreated porcine bioprosthetic aortic valve cusps by 80.0%
      ethanol in rat subdermal implants (60-day ethanol-pretreated calcium level, 1.87
      +/- 0.29 micrograms/mg tissue compared with control calcium level, 236.00 +/-
      6.10 micrograms/mg tissue) and in sheep mitral valve replacements (ethanol
      pretreated calcium level, 5.22 +/- 2.94 micrograms/mg tissue; control calcium
      level, 32.50 +/- 11.50 micrograms/mg tissue). The mechanism of ethanol inhibition
      may be explained by several observations: ethanol pretreatment resulted in an
      irreversible alteration in the amide I band noted in the infrared spectra for
      both purified type I collagen and glutaraldehyde cross-linked porcine aortic
      leaflets. Ethanol pretreatment also resulted in nearly complete extraction of
      leaflet cholesterol and phospholipid. CONCLUSIONS: Ethanol pretreatment of
      glutaraldehyde cross-linked porcine aortic valve bioprostheses represents a
      highly efficacious and mechanistically based approach and may prevent calcific
      bioprosthetic heart valve failure.

PMID- 9008468
TI  - Nitric oxide contributes to the progression of myocardial damage in experimental
      autoimmune myocarditis in rats.
AB  - BACKGROUND: Excess amounts of NO produced by an inducible NO synthase (iNOS) in
      response to cytokines may be cytotoxic and can be destructive to tissue. We
      investigated the role of NO in the development of myocardial damage and the
      effects of aminoguanidine (AG), an inhibitor of iNOS, on experimental autoimmune
      myocarditis in rats. METHODS AND RESULTS: Autoimmune myocarditis was induced in
      20 Lewis rats by injection of porcine cardiac myosin. Ten of the 20 rats were
      administered AG. The severity of myocarditis was evaluated by measuring the size
      of myocarditic lesion and serum levels of CK-MB. Serum NO levels were determined
      using the Cd/Cu method. Tissue specimens were immunohistochemically examined for
      iNOS and nitrotyrosine. Histopathological study revealed extensive myocardial
      destruction and massive inflammatory cell infiltration in AG-untreated rats but
      only focal mononuclear cell infiltration in AG-treated rats. The mean percent
      areas of inflammatory lesions in the untreated and treated rats were 56 +/- 13%
      and 3 +/- 2%, respectively (P < .001). NO levels were 102 +/- 23 and 25 +/- 9
      IU/L, respectively (P < .01). CK-MB levels were 68 +/- 13 and 16 +/- 13 nmol/L,
      respectively (P < .01). Superoxide production as measured with an ex vivo
      monitoring system was also significantly decreased in the treated rats.
      Nitrotyrosine relating to the generation of peroxynitrite was detected through
      immunostaining in the inflammatory lesions of untreated rats but not in those of
      treated rats. CONCLUSIONS: Excess amounts of NO produced by iNOS appear to
      contribute to the progression of myocardial damage in myocarditis. AG may prove
      to be useful in the treatment of myocarditis.

PMID- 9008469
TI  - Skeletal muscle ventricles, left ventricular apex-to-aorta configuration. 1 to 11
      weeks in circulation.
AB  - BACKGROUND: Skeletal muscle ventricles (SMVs) have been used in animals in a
      variety of configurations to provide circulatory assistance. Long-term survival
      and function have been demonstrated. Our laboratory recently obtained promising
      short-term hemodynamic data in a left ventricular apex-to-aorta model. METHODS
      AND RESULTS: SMVs were constructed from the left latissimus dorsi muscle in five
      adult mongrel dogs. After a 3-week period of vascular delay and 5 to 7 weeks of
      electrical conditioning, valved conduits were used to connect the left
      ventricular apex to the SMV and the SMV to the descending aorta. The SMV was then
      stimulated to contract during cardiac diastole. Initial measurements showed a
      significant increase in the mean femoral diastolic pressure (62 +/- 6 versus 51
      +/- 5 mm Hg, P < .05). There was also a decrease in the left ventricular tension
      time index (11.5 +/- 2.5 versus 14.6 +/- 2.1 mm Hg.s, P < .05), indicating a
      decrease in the work requirement of the left ventricle. During SMV stimulation,
      the majority of flow (65%) was through the SMV circuit and was associated with
      reversal of flow in the proximal descending thoracic aorta. The longest-surviving
      animal survived 76 days, at which time pressure augmentation was still seen (mean
      femoral diastolic pressure, 63 +/- 0.9 versus 50 +/- 1.2 mm Hg, P < .05).
      CONCLUSIONS: Survival beyond the acute setting is possible with this model.
      Diastolic pressure augmentation can be effectively maintained over time.

PMID- 9008470
TI  - Regulation of spontaneous transient outward potassium currents in human coronary
      arteries.
AB  - BACKGROUND: Spontaneous transient outward potassium currents (STOCs) induce
      myogenic relaxation in small cerebral vessels. We found STOCs in human coronary
      artery vascular smooth muscle cells (VSMCs) and studied their regulation. METHODS
      AND RESULTS: K+ currents were recorded in human coronary VSMCs by current- and
      voltage-clamp techniques. STOCs were recorded in the presence of 200 mumol/L Cd2+
      and 10 mumol/L verapamil, which block voltage-dependent Ca2+ channels. STOCs were
      inhibited by iberiotoxin (100 nmol/L), a selective blocker of Ca(2+)-activated
      potassium channels (BKCa), and disappeared in a Ca(2+)-free bath. Iberiotoxin
      depolarized the VSMCs within 20 minutes from -44 +/- 7 to -18 +/- 5 mV (n = 17).
      The Ca2+ ionophore A23187 increased intracellular Ca2+ and stimulated whole-cell
      BKCa current. Depletion of Ca2+ from the sarcoplasmic reticulum with caffeine (4
      mmol/L) abolished STOCs for several minutes. Ryanodine (50 mumol/L) transiently
      stimulated STOCs but then completely inhibited STOCs within 10 minutes. The
      firing frequency of STOCs was directly correlated with intracellular Na+
      concentrations from 0 to 24 mmol/L. Lowering intracellular Na+ to zero abolished
      STOCs. We next gave monensin (30 mumol/L) to increase intracellular Na+. This
      maneuver resulted in an increase in whole-cell current fluctuations and STOCs.
      Monensin-induced STOCs were abolished by either lowering extracellular Ca2+ to
      zero or chelating Ca2+ intracellularly with BAPTA-AM (30 mumol/L). CONCLUSIONS:
      STOCs resulted from BKCa activity and were dependent on extracellular Ca2+ but
      not significantly on voltage-dependent Ca2+ channels. STOCs were dependent on
      intracellular Na+ and intracellular calcium store refilling state. We suggest
      that Ca2+ entry into the cell through reverse-mode Na+/Ca2+ exchange determines
      calcium store refilling, which in turn regulates STOC generation in human
      coronary VSMCs.

PMID- 9008471
TI  - Simultaneous multisite mapping studies during induced atrial fibrillation in the
      sterile pericarditis model. Insights into the mechanism of its maintenance.
AB  - BACKGROUND: Chronic atrial fibrillation (AF) is thought to be due to multiple,
      simultaneously circulating wavelets. In the canine sterile pericarditis model,
      the mechanisms of maintenance of AF are not yet understood. METHODS AND RESULTS:
      During six induced AF episodes in six dogs with sterile pericarditis, 372
      unipolar electrograms were recorded simultaneously from an electrode array placed
      around both atrial free walls, along with 10 to 24 electrodes from the atrial
      septum, by use of a multiplexing system. Activation maps during 12 consecutive
      100-ms windows were analyzed from an episode of sustained AF in each dog (mean
      duration, 32 +/- 24 minutes). In two dogs, two such activation maps during the
      same episode of AF were analyzed. During AF, multiple unstable reentrant circuits
      (mean number, 1.4 +/- 0.1 per 100-ms analysis window) with very short cycle
      lengths (mean, 111 +/- 8 ms) present primarily in the atrial septum and right
      atrium were responsible for maintenance of AF. The unstable reentrant circuits
      frequently disappeared and re-formed. Wave fronts traveling from one atrium to
      the other and/or from the atrial septum play an important role in re-formation of
      unstable reentrant wave fronts. CONCLUSIONS: In this model of paroxysmal AF,
      unstable reentrant circuits of very short cycle length principally involving the
      atrial septum appear to be critical for maintenance of AF. Some reentrant
      circuits disappear as others re-form, so that at least one reentrant circuit is
      always present. Because the atria cannot follow their very short cycle lengths in
      a 1:1 manner, AF is maintained.

PMID- 9008473
TI  - Images in cardiovascular medicine. Takayusu's arteritis involving the abdominal
      aorta and renal arteries.

PMID- 9008474
TI  - Perioperative cardiovascular evaluation for noncardiac surgery: congenital heart
      diseases and heart diseases in pregnancy deserve better guidelines.

PMID- 9008475
TI  - Ventricular fibrillation interval as an index of ventricular refractoriness: when
      to catch the fibrillation electrograms?

PMID- 9008472
TI  - Coronary microcirculation in health and disease. Summary of an NHLBI workshop.
AB  - This article summarizes a 2-day workshop on the coronary microcirculation held in
      Bethesda, Md, in September 1994 and sponsored by the National Heart, Lung, and
      Blood Institute of the National Institutes of Health. The workshop explored a
      variety of topics pertaining to coronary microvascular physiology and
      pathophysiology. The latest methodologies that are being used to investigate the
      coronary microvasculature, including endoscopic microscopy of the intramural
      coronary microvasculature and micro-x-ray computerized tomography, were
      discussed. The most recent advances in the regulation of the coronary
      microcirculation-for example, myogenic and flow-dependent responses, KATP
      channels, and regional heterogeneity-were reported. The workshop touched on the
      relation of the microcirculation to clinically important conditions and offered
      recommendations for future research in this important area. Comparisons are made
      to recent advances in the peripheral circulation and current gaps in our
      knowledge concerning the coronary microcirculation. In recent years, research on
      the coronary microcirculation has made substantial advances, in part as a result
      of investigations in the peripheral microcirculation but also because of the
      application of unique methodologies. This research is providing new ways to
      investigate abnormalities of myocardial perfusion, an area of inquiry that until
      recently has been limited to examination of coronary pressure-flow relationships.

PMID- 9008476
TI  - Regional hyperinsulinemia does not modulate beta-adrenergic vasodilator action.

PMID- 9008477
TI  - Predictive value of electron beam computed tomography.

PMID- 9008479
TI  - Echocardiographic estimation of mean right atrial pressure: how to obtain an
      estimate in all patients?

PMID- 9008478
TI  - Predictive value of electron beam computed tomography.

PMID- 9008480
TI  - Plasma brain natriuretic peptide as an indicator of left ventricular systolic
      function and long-term survival after acute myocardial infarction.

PMID- 9008481
TI  - Remodeling rather than neointimal formation?

PMID- 9008482
TI  - Arterial baroreflexes and ventricular tachycardia.

PMID- 9008484
TI  - Neurogenetics and primary care.

PMID- 9008483
TI  - Constrictive pericarditis versus restrictive cardiomyopathy.

PMID- 9008485
TI  - Evaluation of neuromuscular symptoms in veterans of the Persian Gulf War.
AB  - OBJECTIVE: To comprehensively evaluate complaints of muscle fatigue, weakness,
      and myalgias in Persian Gulf veterans (PGV). BACKGROUND: Approximately 700,000
      American troops were deployed to the Persian Gulf during Desert Shield and Desert
      Storm. Upon return from the Gulf, some PGV developed unexplained illnesses, and
      special referral centers were established for the evaluation of these patients.
      Among the most common symptoms of these PGV are fatigue, weakness, and myalgias.
      An Institute of Medicine committee recommended further exploration into the
      possible etiologies of these complaints. METHODS: Twenty PGV with severe muscle
      fatigue, weakness, or myalgias that interfered with their daily activities were
      referred for an extensive prospective neuromuscular evaluation. Routine
      laboratory studies included serum creatine kinase (CK), erythrocyte sedimentation
      rate, thyroid function tests, and exercise forearm tests. All patients received
      nerve conduction studies (NCS), repetitive nerve stimulation, quantitative and
      single-fiber electromyography (EMG), and muscle biopsies. RESULTS: Manual muscle
      strength examinations were normal in all patients. Six patients had mildly
      elevated CKs (range 223 to 768 IU/l); otherwise, laboratory tests were
      unremarkable. NCS were normal except in 2 patients with carpal tunnel syndrome.
      Quantitative EMGs were normal. One patient had mildly increased jitter on single
      fiber EMG. Muscle biopsies demonstrated minor nonspecific abnormalities in 5
      patients (i.e., increased central nuclei, rare necrotic fibers, tubular
      aggregates). CONCLUSIONS: Despite severe subjective symptoms, most of our
      patients had no objective evidence of neuromuscular disease. Mildly increased CKs
      or nonspecific histologic abnormalities on muscle biopsy were evident in 8
      patients but were not believed to be clinically significant in most. We found no
      evidence of a specific neuromuscular disorder in any patient. Exposures to toxins
      during the Persian Gulf War were not likely responsible for our patients'
      symptoms.

PMID- 9008486
TI  - Myelopathy among Brazilians coinfected with human T-cell lymphotropic virus type
      I and HIV.
AB  - OBJECTIVE: To determine whether subjects coinfected with HTLV-I and HIV have a
      higher frequency of myelopathy than subjects singly infected with HIV. DESIGN: A
      prospective, nested case-control study of HTLV-I and HIV coinfected (cases) and
      HIV singly infected adults (controls) participating in a prospective HIV cohort
      study at a university hospital outpatient HIV clinic in Rio de Janeiro, Brazil.
      MEASUREMENTS: Subjects were evaluated for evidence of myelopathy by a neurologist
      unaware of their HTLV serologic status. Patients with at least two pyramidal
      signs, such as paresis, hypertonicity or spasticity, hyperreflexia, clonus,
      diminished or absent superficial reflexes, or the presence of pathologic reflexes
      (e.g., Babinski or Hoffmann), were defined as having myelopathy. Myelopathy
      severity was quantified using the Kurtzke Functional Disability Scale (FDS);
      patients with FDS scores > or = 4 were considered to have significant myelopathy.
      Selected patients with myelopathy underwent lumbar puncture for the evaluation of
      intrathecal synthesis of HTLV-I antibodies. RESULTS: Of 15 coinfected subjects,
      11 (73%) had evidence of myelopathy versus 10 of 62 subjects (16%) with HIV
      single infection (adjusted odds ratio [OR] = 13.0, p = 0.00002). When only
      myelopathy patients with FDS scores of > or = 2 or > or = 4 were included, the
      association between coinfection and the presence of myelopathy remained (OR =
      7.3, p = 0.0003 for scores > or = 2; and OR = 8.9 for scores > or = 4, p = 0.04).
      In addition, a higher proportion of coinfected subjects had peripheral neuropathy
      (40%) than controls (16%) (OR = 3.5, p = 0.07). CONCLUSION: Coinfection with HTLV
      I was strongly associated with myelopathy among subjects infected with HIV. The
      relative contribution of HTLV-I versus HIV in the pathogenesis of coinfection
      associated myelopathy is not known. Coinfection may also be associated with
      peripheral neuropathy. Further studies are needed to elucidate the mechanisms of
      coinfection-associated neurologic conditions.

PMID- 9008487
TI  - Clinical course of a cohort in the Cuban epidemic optic and peripheral
      neuropathy.
AB  - Nearly 51,000 Cubans were afflicted during an outbreak of an optic neuropathy
      (ON) and peripheral neuropathy (PN) between 1991 and 1993. We re-examined 14 of
      20 affected individuals 16 months after an initial evaluation. The optic features
      were painless symmetric vision loss with poor visual acuity, color vision loss,
      central or cecocentral scotoma, optic disc pallor, and nerve fiber layer drop
      out. The neurologic symptoms included stocking-glove sensory changes, hearing
      loss, leg cramps, sensory ataxia, hyperactive or absent reflexes, and complaints
      of memory loss. Two of 11 ON probands tested harbored Leber's hereditary optic
      neuropathy (LHON)-associated mitochondrial DNA mutations. All patients had
      received multivitamin therapy. We performed comparisons using the paired two
      tailed t test. On re-examination, 12 of 14 patients demonstrated improvement. One
      patient remained unchanged. One woman with the nt-3460 mtDNA mutation showed a
      decline in vision. In patients not harboring mtDNA mutations, overall visual
      acuity, color vision, and peripheral neuropathy manifestations improved
      significantly (p < 0.001 for each manifestation). Most of the patients with Cuban
      ON and PN improved on multivitamin therapy. The significance of the mtDNA
      mutations is unclear. In the 2 LHON patients, manifestation of the disease may
      have been precipitated by nutritional deficiency. Patients with poor recovery or
      further deterioration should be evaluated for other factors, including poor
      vitamin therapy compliance and alternative diagnoses.

PMID- 9008488
TI  - Hereditary motor and sensory neuropathy IIB: clinical and electrodiagnostic
      characteristics.
AB  - Axonal forms of autosomal dominant hereditary motor and sensory neuropathies
      (HMSNs) represent a heterogeneous group of disorders based on genetic linkage
      studies. We recently identified one large family with axonal HMSN exhibiting
      linkage to chromosome 3q, designated HMSN IIB, and report here the clinical and
      electrodiagnostic features. We clinically evaluated 10 individuals with HMSN IIB
      and performed detailed electrophysiologic studies in 5 of these patients. HMSN
      IIB is characterized clinically by the presence of distal symmetric motor
      weakness and prominent sensory loss affecting the lower extremities with
      preserved ankle reflexes. Symptomatic age at onset is in the second or early
      third decade of life. Six patients with HMSN IIB had distal trophic ulcerations
      in the feet, leading to eventual toe amputations in four cases. Electrodiagnostic
      studies confirmed a distal sensorimotor axonopathy involving the lower limbs with
      normal motor conduction velocities. Tibial H-reflexes were preserved in HMSN IIB,
      despite the uniform loss of sural nerve potentials. Overall, individuals with
      HMSN IIB demonstrated a consistent clinical and electrodiagnostic phenotype that
      had no overlap with genetically unaffected family members. The identification of
      specific clinical and electrodiagnostic features of HMSN IIB may prove useful in
      the diagnosis and differentiation between various subtypes of HMSN II.

PMID- 9008489
TI  - Inclusion body myositis: no evidence for a neurogenic component.
AB  - Because electrophysiologic, clinical, and histopathologic observations have
      suggested that inclusion body myositis (IBM) may have a coexistent neurogenic
      component, we used macro-electromyography (macro-EMG) to search for changes in
      the motor unit territory and signs of reinnervation. We studied 11 patients, aged
      53 to 77 years (mean, 65.2 years), with typical, nonfamilial IBM lasting a mean
      of 8.5 years, and eight healthy volunteers aged 54 to 70 years (mean, 64.6
      years), as control subjects. Nerve conduction studies showed focal abnormalities
      in 5 of the patients, but no evidence of a polyneuropathy. Concentric needle EMG
      in various proximal and distal muscles of the upper and lower limbs revealed
      short- or long-duration complex motor unit potentials (MUPs) or a mixture of both
      types of MUPs. Macro-EMG studies in the tibialis anterior muscle showed smaller
      macro-MUP amplitudes and areas in patients than in normal subjects. Four patients
      had abnormal macro-EMG studies with an increased number of small macro-MUPs, 1
      patient had an equivocal study with large-amplitude but normal-area macro-MUPs,
      and the remaining 6 patients had normal studies. These findings are consistent
      with a primary muscle disorder similar to those seen in other myopathies. We
      conclude that macro-EMG does not support a coexistent neurogenic component in
      patients with IBM compared with normal subjects of similar age.

PMID- 9008490
TI  - Proximal myotonic myopathy with MRI white matter abnormalities of the brain.
AB  - Proximal myotonic myopathy (PROMM) is an autosomal dominantly inherited
      multisystemic disorder characterized by myotonia, proximal muscle weakness, and
      cataracts. This disorder is not linked to the gene locus of myotonic dystrophy
      (DM). We describe three new families with PROMM. In all patients, CTG repeats of
      the DM gene in DNA from blood leukocytes were normal. MRI of the brain revealed a
      consistent pattern of marked white matter hyperintensity on T2-weighted images in
      four patients; two additional patients had similar but mild to moderate MRI
      abnormalities. The morphology of these abnormalities is unknown. Clinical
      symptoms of brain disease were not consistent and included mental changes with
      hypersomnia, parkinsonian features, stroke-like episodes, and seizures. The
      causative relationship of these clinical features with the MRI white matter
      abnormalities remains to be established. Our observations suggest that PROMM may
      involve the brain.

PMID- 9008491
TI  - A prospective, quantitative study of the natural history of facioscapulohumeral
      muscular dystrophy (FSHD): implications for therapeutic trials. The FSH-DY Group.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder
      localized to 4q35. Neither the gene nor the gene product has been identified.
      There is presently no established treatment for FSHD. Prospective data on the
      natural history of this disorder are essential for the effective design of
      therapeutic trials. We systematically followed 81 well defined FSHD patients for
      up to 3 years using a standardized protocol that included manual muscle testing
      (MMT), maximum voluntary isometric contraction testing (MVICT), and functional
      testing. Muscle strength was strongly associated with measures of muscle mass,
      age at onset, and duration of disease. Decline in strength over time was slow but
      detectable with both MVICT and MMT. The magnitude of decline was not associated
      with either age, gender, age at onset, or duration of disease. This study
      establishes reliable and valid measures of disease state and progression for use
      as outcome variables in clinical trials in FSHD, and also provides guidelines for
      determining sample size and duration of follow-up. A two-armed clinical trial
      involving 160 patients per group and 1 year of follow-up would provide 80% power
      to detect complete arrest of the progression of the disease. Trials with fewer
      patients would thus have adequate power to detect only improvements in strength,
      unless follow-up duration were extended well beyond 1 year.

PMID- 9008492
TI  - A pilot trial of prednisone in facioscapulohumeral muscular dystrophy. FSH-DY
      Group.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant, 4q35
      linked, slowly progressive muscular dystrophy with no known effective treatment.
      Since prednisone improves strength in Duchenne dystrophy, we performed a pilot,
      open-label trial of prednisone in eight subjects fulfilling strict diagnostic
      criteria for FSHD. Prednisone (1.5 mg/kg/day; maximum 80 mg/day) was administered
      for 12 weeks. Manual muscle testing, maximum voluntary isometric contraction
      testing, and muscle mass estimations by dual energy x-ray absorptiometry and
      urinary creatinine excretion were performed at baseline and at 12 weeks. There
      were no significant changes in strength or muscle mass. We conclude that
      prednisone given for 12 weeks does not produce major improvement in strength or
      increase muscle mass in FSHD. The study did not have sufficient power or length
      of follow-up to address the possibility that prednisone might arrest or slow
      disease progression.

PMID- 9008493
TI  - The fetal/adult acetylcholine receptor antibody ratio in mothers with myasthenia
      gravis as a marker for transfer of the disease to the newborn.
AB  - High anti-fetal/anti-adult muscle anti-acetylcholine receptor (AChR) antibody
      (Ab) titer ratio is predictive of the occurrence of neonatal myasthenia gravis in
      a first child. The aim of the present study was to determine whether the ratio
      between the levels of antibodies is an intrinsic property of the mother's sera or
      varies with physiologic status such as pregnancy. We performed a longitudinal
      study of the levels of Ab directed against both fetal and adult AChRs and the
      ratio between them in 11 mothers with myasthenia gravis (MG). Sera were taken
      during, before, and after pregnancy. Absolute levels of Ab varied considerably
      during the time of observation as indicated by analyzing the maximum change
      between any two sample times during the study (adult mean percentage change 45.9
      +/- 26.4; fetal 42.51 +/- 22.05). In contrast to this, the anti-fetal/anti-adult
      muscle AChR Ab titer ratio was much less variable (mean percentage change 16.66
      +/- 10.11; p < 0.0033). The levels of the two Ab types yielded a correlation of
      0.918, consistent with the stability of the ratio between them. This stability of
      ratio has practical value in the management of pregnancy and infant care in
      mothers with MG because the ratio at any time, before or during pregnancy, will
      predict whether the child will contract neonatal MG. We determined this for the
      first child, but further studies are necessary to establish if this remains true
      for subsequent pregnancies.

PMID- 9008494
TI  - Prognosis in familial amyotrophic lateral sclerosis: progression and survival in
      patients with glu100gly and ala4val mutations in Cu,Zn superoxide dismutase.
AB  - Familial amyotrophic lateral sclerosis (FALS) is an autosomal dominant
      neurodegenerative disorder affecting motor neurons and is associated with
      mutations in the Cu,Zn superoxide dismutase gene (SOD1) in a subset
      (approximately 15%) of FALS families. We analyzed 158 FALS patients from 27
      families with mutations in SOD1. The mean age of onset was 45.5 +/- 8.9 years,
      and the mean duration of disease was 3.4 years. Forty-seven different mutations
      in SOD1 of FALS patients have been described worldwide. In North America, the
      ala4val mutation is the most common. In our patients, the ala4val mutation was
      associated with the most rapid progression of disease. The mean duration of
      disease was 1.0 +/- 0.4 years, which is significantly less than the mean duration
      of disease for FALS patients with mutations in SOD1 other than ala4val (p <
      0.001). The duration of disease for the glu100gly mutation, 5.1 +/- 3.3 years,
      was significantly longer than the ala4val mutation (p < 0.001). We constructed
      Kaplan-Meier survival curves for the age of onset and duration of the disease for
      three groups of patients having mutations in SOD1: (1) ala4val; (2) glu100gly;
      and (3) ala4val, gly37arg, his43arg, gly85arg, gly93ala, glu100gly, leu106val,
      ile113thr, leu144phe, and val148gly, i.e., the entire patient population. There
      was no correlation between the genotype and the age of onset; 50% of affected
      individuals developed symptoms of ALS by the age of 47 years. As more data are
      collected, a more accurate prognostication of a patient's survival may be
      possible for specific SOD1 mutations.

PMID- 9008495
TI  - Recurrent optic neuromyelitis with endocrinopathies: a new syndrome.
AB  - We report a new syndrome that we call "recurrent optic neuromyelitis with
      endocrinopathies" in eight Antillean women from Martinique and Guadeloupe Ocular
      involvement was either monocular or binocular, whereas myelopathy was acute or
      subacute. In seven patients, myelopathic symptoms recurred, and in six patients,
      visual problems recurred. Spinal cord involvement was a consistent band-like
      pseudo-syringomyelic dissociated sensory loss. All eight patients had
      endocrinopathies consisting of amenorrhea, galactorrhea, diabetes insipidus,
      hypothyroidism, or hyperphagia. Spinal cord MRI revealed cavitation-like images.
      Various immunosuppressant treatments had little effect on the uniformly
      deteriorating course, ending in blindness and paraplegia. Six patients died
      within 5 years of onset, and an autopsy in one patient showed multiple
      demyelinizing lesions of the spinal cord with thickened blood vessels walls
      without evidence of inflammation. These cases appear to constitute a syndrome
      distinct from MS and from classic Devic's syndrome, not only because of the
      association with endocrinopathies but because of the stereotypy of the
      recurrences, the absence of MRI lesions in the cerebral white matter, and the
      unusual image of cavitation of the spinal cord. The syndrome is also distinct
      from HTLV-I-associated paraparesis, which is endemic in the West Indies.

PMID- 9008496
TI  - Multiple sclerosis presenting as transverse myelopathy: clinical and MRI
      features.
AB  - We described specific MRI features of MS presenting with acute partial transverse
      myelopathy. We reviewed the clinical histories and MRI studies of brain and
      spinal cord of 24 patients, using axial and sagittal images of the spinal cord to
      define patterns of signal abnormality in the context of clinical presentation,
      course, and vertebral column structural pathology. The heterogeneity of spinal
      cord tract involvement was greater than previously reported, with signal
      abnormality identified within the central cord, crossing the gray-white junction,
      and involving all four major funiculi. Correlation between spinal cord MRI
      findings and neurologic deficits was strong (100% by axial images; 96% by
      sagittal images). Serial spinal cord MRI demonstrated the dynamic nature of the
      signal abnormalities over time and in response to high-dose steroid treatment. No
      cranial MRI abnormality initially was seen in 36% of cases with evidence of
      demyelinating disease on concurrent spinal MRI.

PMID- 9008497
TI  - Quality of life among persons with multiple sclerosis and their caregivers.
AB  - For those with a chronic illness, suffering may result not only from physical
      limitations, but also from the psychosocial consequences of having a chronic
      condition. Few studies have described the psychosocial characteristics of the
      physically disabled. Even more rare are population-based studies of quality of
      life (QOL) among persons with multiple sclerosis (MS) and their caregivers. We
      conducted a large survey of persons with MS and their caregivers in Ontario using
      self-completed mailed questionnaires. The objectives included describing
      satisfaction with QOL and determining relationships between QOL as a whole and
      several other factors, such as demographic characteristics and measures of
      physical disability. Response rates were 83% for those with MS and 72% for their
      caregivers. Based on 697 respondents with MS, mean age was 48 years, 70% were
      women, and 75% were married. While 24% experienced no mobility restrictions, the
      majority required some type of aid or a wheelchair for getting around. Health
      received the lowest satisfaction rating among the six components of QOL, while
      finances received a relatively low satisfaction rating from the 345 caregivers.
      Less satisfaction with several QOL components was evident for those with MS
      compared with the disabled in the Canadian general population, and for caregivers
      compared with the able-bodied general population. Poorer QOL as a whole among
      those with MS was associated with unemployment, MS symptoms of moderate or worse,
      fatigue, mobility limitations on stairs, a disease course other than stable, and
      was most strongly related to interference by MS in social activities. Among
      caregivers, poorer QOL as a whole was associated with being a spouse, longer
      duration of caregiving, moderate or worse MS symptoms in the care recipient, and
      most strongly related to a care recipient's current MS disease course of other
      than stable. Through an understanding of the satisfaction with QOL of persons
      with MS and caregivers, and the relationships with other important factors,
      autonomy and home care may be supported and prolonged, while preventing
      unnecessary institutionalization.

PMID- 9008498
TI  - Tolcapone improves motor function and reduces levodopa requirement in patients
      with Parkinson's disease experiencing motor fluctuations: a multicenter, double
      blind, randomized, placebo-controlled trial. Tolcapone Fluctuator Study Group I.
AB  - Tolcapone is a potent catechol-O-methyltransferase inhibitor that prolongs the
      plasma half-life of levodopa. This multicenter, double-blind, placebo-controlled
      study used two 10-hour clinical evaluations to compare the efficacy and safety of
      three doses of tolcapone (50, 200, and 400 mg tid) with placebo in patients with
      Parkinson's disease (PD) experiencing motor fluctuations from levodopa/carbidopa.
      One hundred fifty-one patients completed the study. Clinical evaluations lasting
      10 hours were performed on day -1 and day 42 using United Parkinson's Disease
      Rating Scale motor subscale and "on/off" and dyskinesia assessments every 30
      minutes. Tolcapone significantly reduced "off" time an average of 40% and
      increased total "on" time by about 25% at all dose levels, as compared to placebo
      treatment. Levodopa/carbidopa dosage and frequency were significantly reduced.
      Tolcapone was well tolerated, with patients experiencing typical dopaminergic
      side effects that could be reduced or eliminated by lowering levodopa/carbidopa
      dosages. Tolcapone was effective at prolonging the clinical benefit of levodopa
      and reducing total levodopa requirements in PD patients with motor fluctuations.

PMID- 9008499
TI  - Free-living daily energy expenditure in patients with Parkinson's disease.
AB  - Previous studies have suggested that elevated resting energy expenditure
      contributes to weight loss in patients with Parkinson's disease (PD). Body weight
      is, however, ultimately determined by variation in daily energy expenditure and
      not just resting energy expenditure. Therefore, we examined the hypothesis that
      PD patients are characterized by elevated daily energy expenditure. Sixteen
      patients with levodopa responsive PD and 46 healthy elderly controls were
      characterized for daily energy expenditure and its components (resting and
      physical activity energy expenditure) using a combination of the doubly labeled
      water technique (over 10 days) and resting indirect calorimetry. Fat-free mass
      and fat mass were measured by dual energy x-ray absorptiometry. Results showed
      that fat mass and fat-free mass did not differ between groups. Daily energy
      expenditure was 15% lower (2214 +/- 460 vs. 2590 +/- 497 kcal/d; p < 0.01) in PD
      patients compared to controls. This was primarily due to lower physical activity
      energy expenditure (339 +/- 366 vs. 769 +/- 412 kcal/d; P < 0.01) in PD patients
      as resting energy expenditure was not different between groups (1655 +/- 283 vs.
      1561 +/- 219 kcal/d). These results show that daily energy expenditure is lower
      in PD patients compared to healthy elderly, primarily due to reduced physical
      activity energy expenditure. These results argue against the hypothesis that an
      abnormally elevated daily energy expenditure contributes to weight loss in PD.

PMID- 9008500
TI  - Anticardiolipin antibodies and the risk of recurrent thrombo-occlusive events and
      death. The Antiphospholipid Antibodies and Stroke Study Group (APASS).
AB  - We tested the hypothesis that an anticardiolipin antibody (aCL) titer of > or =
      10 IgG phospholipid (GPL) at the time of an index ischemic stroke is associated
      with an increased risk of subsequent thrombo-occlusive events or death. First
      time ischemic stroke patients from the Antiphospholipid Antibodies and Stroke
      Study Group's Prevalence Study were followed prospectively for a median time of
      24 months for any thrombo-occlusive event or death. There was no significant
      difference for the endpoint of stroke, death, myocardial infarction, transient
      ischemic attack, deep venous thrombosis, pulmonary embolus, or arterial embolus
      between the aCL positive and negative patients. Although a single aCL value of >
      or = 10 GPL at the time of an initial ischemic stroke is a significant
      independent risk factor for stroke, when adjusted for other stroke risk factors
      in our study population, aCL positivity did not confer a significantly increased
      risk for subsequent thrombo-occlusive events or death.

PMID- 9008501
TI  - Patients with stroke confined to basal ganglia have diminished response to
      rehabilitation efforts.
AB  - Prediction of the functional outcome for patients with stroke has depended on the
      severity of impairment, location of brain injury, age, and general medical
      condition. This study compared admission and discharge functional outcome
      (Functional Independence Measure, FIM) and deficit severity (Fugl-Meyer, F-M)
      scores in a retrospective study of patients with similar neurologic impairments:
      homonymous hemianopia, hemisensory loss, and hemiparesis. CT-verified stroke
      location was the independent variable: cortical (n = 11), basal ganglia and
      internal capsule (normal cortex and thalamus, n = 13), or combined (cortical,
      basal ganglia, and internal capsule, n = 22). By 3 months on average after
      stroke, all groups demonstrated significantly improved motor function as measured
      by F-M scores. Patients with cortical lesions had the least CT-imaged damage and
      the best outcome. Patients with combined lesions and more extensive brain injury
      had significantly higher FIM scores (P < 0.05) than patients with injury
      restricted to the basal ganglia/ internal capsule. Patients with basal
      ganglia/internal capsule injury were more likely to have hypotonia, flaccid
      paralysis, and persistently impaired balance and ambulation performance. While
      all patients had a comparable rehabilitation experience, these results suggest
      that patients with stroke confined to the basal ganglia and internal capsule
      benefited less from therapy. Isolated basal ganglia stroke may cause persistent
      corticothalamic-basal ganglia interactions that are dysfunctional and impede
      recovery.

PMID- 9008502
TI  - Continuous bromocriptine therapy in menstrual migraine.
AB  - This investigation assessed the effects of an open, prospective trial of
      adjunctive continuous bromocriptine therapy on the frequency of refractory,
      disabling menstrual migraine. It compared continuous bromocriptine with
      previously optimal baseline therapy and cyclic perimenstrual bromocriptine use.
      The subjects were 24 women with disabling migraines that occurred exclusively or
      at least 50% of the time within 3 days before or after the onset of menstruation
      despite treatment. We added bromocriptine 2.5 mg three times a day to their
      existing regimen and compared menstrual migraine frequency during the first year
      with the year prior to bromocriptine. Eighteen of the 24 women experienced a 25%
      or greater decline in migraine frequency. Migraine frequency declined by 72%
      overall (p < 0.01). Three women did not tolerate bromocriptine, and three did not
      benefit. None of the women had a 10% or greater increase in headaches. Continuous
      bromocriptine therapy was also significantly more effective than intermittent
      bromocriptine use (p < 0.05). Continuous bromocriptine therapy appears to benefit
      menstrual migraine.

PMID- 9008503
TI  - Ibuprofen or acetaminophen for the acute treatment of migraine in children: a
      double-blind, randomized, placebo-controlled, crossover study.
AB  - Efficacy of drugs for the acute treatment of migraine in children has not so far
      been studied in well controlled trials. We conducted a study to evaluate the
      efficacy of acetaminophen and ibuprofen. Eighty-eight children, aged 4.0 to 15.8
      years, with migraine participated in a double-blind crossover study. Three
      attacks per child were treated in random order with single oral doses of 15 mg/kg
      acetaminophen, 10 mg/kg ibuprofen, and placebo at home. The primary end point,
      reduction in severe or moderate headache (grade > or = 3 on a scale of 1 to 5) by
      at least two grades after 2 hours, was reached twice as often with acetaminophen
      and three times as often with ibuprofen as with placebo. Ibuprofen was twice as
      likely as acetaminophen to abort migraine within 2 hours. In the intent-to-treat
      analysis, children improved twice as often with ibuprofen and acetaminophen as
      with placebo. Both ibuprofen and acetaminophen are effective and economical
      treatments for severe or moderate migraine attacks in children. Ibuprofen gave
      the best relief.

PMID- 9008504
TI  - Cognitive processing in primary headache: a study on event-related potentials.
AB  - BACKGROUND: There is experimental evidence for loss of cognitive habituation in
      migraine but not in other types of headache and not by visual event-related
      potentials (ERP). OBJECTIVE: Determining the latencies (msec) and amplitudes
      (microV) of ERP components and the differences of these values in a two-trial
      analysis representing the amount of cognitive habituation. PARTICIPANTS: Two
      hundred thirty-three patients with a headache diagnosis according to the criteria
      of the International Headache Society: migraine without aura (N = 77); migraine
      with aura (N = 31); cluster headache during period (N = 26); cluster headache
      during interval (N = 11); chronic paroxysmal hemicrania (N = 8); episodic tension
      type headache (N = 33); ergotamine-induced headache (N = 47). Thirty age-matched
      healthy subjects served as a control group. METHODS: ERPs were evoked by a visual
      oddball paradigm consisting of 2 x 200 flashes of light (85% white light; 15% red
      light). Evaluation of ERP components was done separately for the first 200 and
      the second 200 stimuli as well as for the entire series of stimuli. RESULTS: We
      found an acceleration of the P3 latency during the second trial in migraine with
      and without aura, but not in the other headache types, and not in healthy
      controls. Ergotamine and sumatriptan abolished this loss of habituation in
      migraine patients. Increased ERP latencies as compared with healthy controls were
      present in patients with cluster headache, tension-type headache, ergotamine
      induced headache, and migraine with aura, but not in migraine without aura.
      CONCLUSION: There is a loss of cognitive habituation in migraine, which may serve
      as a specific but not sensitive diagnostic tool. The pathophysiologies of
      migraine and cluster headache have a specific modifying property on cognitive
      processing reflected by a loss of cognitive habituation or an increased cognitive
      processing time. These effects can, in part, be counterbalanced by antimigraine
      medication.

PMID- 9008505
TI  - Phosphorus magnetic resonance spectroscopy in cluster headache.
AB  - We performed in vivo MR spectroscopy phosphorus (31P-MRS) on the brain and
      skeletal muscles of 14 patients affected with cluster headache (CH). We examined
      patients in interictal periods, and also examined nine of them during the cluster
      period, although not during the attack. Brain 31P-MRS showed reduced
      phosphocreatine (PCr) levels, an increased ADP concentration (calculated from the
      creatine kinase equilibrium), a reduced phosphorylation potential, and a high
      relative rate of ATP biosynthesis (V/Vmax %). The inorganic phosphate (P(i))
      content was increased during the cluster period. Ten of 13 patients also showed a
      slow rate of PCr recovery in muscle after the exercise. 31P-MRS in CH patients
      showed abnormalities of brain and skeletal muscle energy metabolism comparable
      with those seen in various types of migraine, thus leading us to suggest a
      similarity in biochemical pathogenic mechanisms between CH and migraine.

PMID- 9008506
TI  - Accuracy of the clinical diagnosis of corticobasal degeneration: a
      clinicopathologic study.
AB  - The accuracy of the clinical diagnosis of corticobasal degeneration (CBD) is
      unknown. To determine its diagnostic accuracy, we presented 105 cases with known
      neuropathologic diagnoses, including CBD (n = 10), progressive supranuclear palsy
      (PSP, n = 24), Parkinson's disease (n = 15), diffuse Lewy body disease (n = 14),
      multiple system atrophy (n = 16), postencephalitic parkinsonism (n = 7), Pick's
      disease (n = 7), Creutzfeldt-Jakob disease (n = 4), Alzheimer's disease (n = 4),
      vascular parkinsonism (n = 3), and Whipple's disease (n = 1), as clinical
      vignettes to six neurologists unaware of the autopsy findings. Reliability was
      measured with the kappa statistics. The neurologists' clinical diagnoses were
      compared with clinicopathologic diagnoses for sensitivity, specificity, and
      positive predictive values at first and last clinic visits. The group reliability
      for the diagnosis of CBD significantly improved from moderate for the first visit
      (mean = 34 months after onset) to substantial for the last (68 months after
      onset). For the first visit, mean sensitivity for CBD was low (35%), but
      specificity was near-perfect (99.6%). For the last visit, mean sensitivity
      minimally increased (48.3%), and specificity remained stable. False-negative
      misdiagnoses mainly occurred with PSP. False-positive diagnoses were rare. The
      extremely low sensitivity of the clinical diagnosis of CBD suggests that this
      disorder is markedly underdiagnosed. Although the validity of the clinical
      diagnosis might have been improved if neurologists could have examined these
      patients, more important is that this disorder was misdiagnosed by the primary
      neurologists. In our data set, the best predictors for the diagnosis of CBD
      included limb dystonia, ideomotor apraxia, myoclonus, and asymmetric akinetic
      rigid syndrome with late onset of gait or balance disturbances.

PMID- 9008507
TI  - Criteria for Alzheimer's disease and the nosology of dementia with Lewy bodies.
AB  - Dementia with brainstem and neocortical Lewy bodies (LB) is a source of ongoing
      nosologic controversy and confusion. Differing opinions about concomitant
      Alzheimer's disease (AD) have produced competing nomenclatures. We applied
      neocortical plaque-based criteria for the diagnosis of AD from the National
      Institute on Aging and from the Consortium to Establish a Registry for AD for
      definite, probable, and possible AD to 58 dementia brains with LB, 10 elderly
      nondemented controls, and 58 brains with neuropathologically pure AD. We also
      employed diagnostic criteria requiring both neocortical plaques and tangles, and
      assessed the extent of neurofibrillary pathology in all 126 specimens using a
      modified version of the Braak and Braak staging protocol for changes related to
      AD. The percentages of mixed LB disease and AD versus pure LB disease varied from
      91% mixed and 9% pure to 34% mixed and 66% pure, depending upon which diagnostic
      criteria for AD were employed. Most dementia brains with LB occupied higher
      modified Braak stages than controls, but lower ones than pure AD specimens. A
      minority of the dementia brains with LB had no more AD-type pathology than
      controls.

PMID- 9008508
TI  - Very old women at highest risk of dementia and Alzheimer's disease: incidence
      data from the Kungsholmen Project, Stockholm.
AB  - OBJECTIVE: To determine the incidence of different types of dementia in the very
      old, and to explore the relation with age and gender. DESIGN: A dementia-free
      cohort was followed for an average of three years in Stockholm, Sweden. At the
      end of the follow-up, the subjects were interviewed by nurses, clinically
      examined by physicians, and cognitively assessed by psychologists. Deceased
      cohort members were studied using death certificates, hospital clinical records,
      and discharge diagnoses. Dementia diagnoses were made according to the DSM-III-R
      criteria independently by two physicians. PARTICIPANTS: The cohort consisted of
      1,473 subjects (75+ years old), of which 987 were clinically examined at follow
      up, 314 died before the examination, and 172 refused to participate. RESULTS:
      During the follow-up, 148 subjects developed dementia. In the age-group 75 to 79,
      the incidence rates for dementia were 19.6 for women and 12.4 for men per 1,000
      person-years, whereas for 90+ year-old subjects the corresponding figures were
      86.7 and 15.0 per 1,000 person-years. A similar pattern of distribution by age
      and gender was seen for Alzheimer's disease. In each age stratum, the incidence
      rates of dementia and Alzheimer's disease were higher for women than for men. The
      age-adjusted odds ratio for women was 1.9 for dementia and 3.1 for Alzheimer's
      disease. CONCLUSIONS: (1) The incidence of dementia increases with age, even in
      the oldest age groups; (2) women have a higher risk of developing dementia than
      men, especially at very old ages; (3) this pattern is mainly due to the age and
      gender distribution of Alzheimer's disease, rather than vascular dementia.

PMID- 9008509
TI  - ApoE-4 and age at onset of Alzheimer's disease: the NIMH genetics initiative.
AB  - OBJECTIVE: To explore the impact of apoE-4 on Alzheimer's disease (AD) and its
      age at onset. DESIGN: A genetic linkage study using affected relative pairs,
      predominantly siblings. SETTING: Three academic medical centers ascertained
      subjects from memory disorder clinics, nursing homes, and the local community.
      SUBJECTS: 310 families including 679 subjects with AD by NINCDS/ADRDA and/or
      Khachaturian criteria and 231 unaffected subjects. OUTCOME MEASURE: ApoE
      genotype. ANALYTIC METHODS: Association, affected pedigree member, sibling pair,
      and lod score analyses. RESULTS: ApoE-4 was strongly associated with AD in this
      sample (allele frequency = 0.46 vs. 0.14 in controls, p < 0.000001). Results of
      lod score, affected pedigree member analysis, and sib-pair analysis also
      supported apoE-4 as a risk factor for AD. When the sample was stratified on
      family mean age at onset, the risk conferred by apoE-4 was most marked in the 61
      to 65 age group. Individuals with two copies of apoE-4 had a significantly lower
      age at onset than those with one or no copies (66.4 vs. 72.0, p < 0.001), but
      individuals with one copy did not differ from those with none. Within families,
      the individual with the earliest age at onset had, on average, significantly more
      apoE-4 alleles (p < 0.0001) than the individual with the latest onset.
      DISCUSSION: This work supports previous reports of an association between apoE-4
      and the development of AD and demonstrates that apoE-4 exerts its maximal effect
      before age 70. These findings have important implications for the potential use
      of apoE genotyping for diagnosis and prediction of disease. They also underscore
      the need to identify additional genetic factors involved in AD with onset beyond
      age 70 years.

PMID- 9008510
TI  - Decline of frontal lobe functions in subjects with age-associated memory
      impairment.
AB  - OBJECTIVE: To assess frontal lobe functions of subjects with age-associated
      memory impairment (AAMI) and to examine whether performance on neuropsychological
      tests is correlated with the volume of the frontal lobes in magnetic resonance
      imaging. DESIGN: Cross-sectional two-group comparison. SETTING: The Memory
      Research Clinic of Kuopio University and the Magnetic Resonance Imaging Center of
      Kuopio University Hospital. PARTICIPANTS: Ninety subjects (mean age, 70.5 years),
      43 with AAMI diagnosed according to National Institute of Mental Health criteria
      and 47 age-matched healthy controls. MEASUREMENTS: Four neuropsychological tests
      were used to assess frontal lobe function: Verbal Fluency Test (VFT), Modified
      Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Stroop Test
      (ST). A 1.5-T magnetic resonance imager was used for volume measurements.
      RESULTS: The AAMI subjects scored significantly worse on the WCST, ST, and TMT
      compared with controls (ANCOVA, adjusted for age and education, p < 0.05). The
      frontal lobe volumes did not differ between AAMI subjects and controls.
      CONCLUSIONS: AAMI subjects appear to be impaired not only in tests assessing
      memory but also in tests of executive functions. This finding agrees with
      previous reports suggesting a central role for frontal dysfunction in memory loss
      of elderly people.

PMID- 9008511
TI  - Hippocampal sclerosis contributes to dementia in the elderly.
AB  - OBJECTIVE: To assess the relevance of hippocampal sclerosis (HS) to dementia in
      the elderly. BACKGROUND: HS is a prominent pathologic finding in some demented
      elderly, but the anatomic substrate and cognitive profiles of this dementia have
      not been well established. DESIGN/METHODS: An autopsy series, including dot
      immunobinding assay to estimate neocortical synaptic density, of eight patients
      (three men, five women) with HS on whom extensive antemortem neuropsychological
      testing was available. RESULTS: Mean age at onset was 72.0 (+/-9.8) (range, 59 to
      89) with a mean duration of symptoms of 6.5 (+/-2.9) years. Patients were only
      mildly impaired with a mean MMSE of 20.9 (+/-4.9) and a mean DRS of 103.1 (+/
      12.5) at presentation. Cardiovascular disease was present in 88%, with a mean
      Hachinski score of 3.4 (+/-2.2). No patient had a history of seizures. Sixty
      three percent had depression or depressive symptoms. Neuropsychologically, most
      patients presented with prominent memory and language deficits and became
      progressively demented. Neuropathologically, isolated HS was a rare finding; many
      patients had either very mild or neocortical "plaque only or plaque predominant"
      Alzheimer's disease (AD) in addition to HS changes. Midfrontal neocortical
      synaptophysin counts were significantly reduced in all HS patients compared with
      controls (p = 0.0006). CONCLUSIONS: In the elderly, HS can be a neuropathologic
      substrate of dementia. Clinically, it can be associated with a course that is
      difficult to distinguish from AD although cardiac disease and depression are
      frequent concomitants. Deterioration of cognitive function in these subjects may
      relate to other pathologic features such as neocortical synapse loss.

PMID- 9008512
TI  - Amnesia following damage to the mammillary bodies.
AB  - It is not known whether lesions of the mammillary body per se can produce
      significant memory impairment in humans. The amnesia reported in patients with
      lesions in the mammillary bodies may have been produced by lesions coexisting in
      other memory-related areas, such as the medial thalamus, mammillothalamic tract,
      descending columns of the fornix, or amygdalofugal pathways. We describe a
      patient who developed anterograde amnesia following damage to the basal
      hypothalamus involving the mammillary bodies. The cause was a cystic
      craniopharyngioma. After surgical removal of the tumor, his memory function
      improved but remained considerably impaired, especially on delayed recall.
      Postsurgical MRI revealed small, atrophic mammillary bodies without residual
      tumor. There was no obvious evidence of damage to the hypothalamus. We therefore
      conclude that our patient's amnesia resulted from mammillary body lesions alone.

PMID- 9008513
TI  - Specific semantic memory loss after hypoxic-ischemic injury.
AB  - A patient is reported who suffered hypoxic-ischemic injury causing isolated and
      eventually partially reversible semantic memory loss. Despite normal MRI
      findings, single-photon emission CT demonstrated dysfunction in posterior
      cortical association areas. Semantic memory is the sum of categorical,
      perceptual, and conceptual knowledge. While not localized in a strict sense like
      visual fields, semantic memory is thought to be broadly organized in the
      posterior association cortices, with a particular focus in the inferior temporal
      regions. Evidence for this has come from patients with herpes simplex
      encephalitis, temporo-occipital infarctions, and dementias. This case confirms
      the importance of these cortical regions for semantic memory. The rapid recovery
      in this case, as opposed to the encephalitis or infarction cases, suggests an
      important role for preservation of white matter connections in the region for
      reconstitution of function.

PMID- 9008514
TI  - Age-related reduction in functional MRI response to photic stimulation.
AB  - Many functional imaging studies have demonstrated age-related alterations in
      cerebral blood flow during the resting state. However, few studies have addressed
      possible differences in functional response to cerebral activation. We assessed
      the response of visual cortex to photic stimulation in 9 normal elderly subjects
      and 17 normal younger subjects with blood oxygenation level dependent functional
      magnetic resonance imaging. We found that the amplitude of response in elderly
      subjects was significantly decreased compared to younger subjects (2.5 +/- 1.0%
      versus 4.0 +/- 1.6%, p = 0.01), suggesting a reduction in functional activation
      or an age-related alteration in the coupling of blood oxygenation to focal
      activation.

PMID- 9008515
TI  - Prevalence and genetics of sleepwalking: a population-based twin study.
AB  - We investigated the prevalence of sleepwalking using a well defined population
      previously used for epidemiologic investigations: the Finnish Twin Cohort. The
      study population consisted of 11,220 subjects aged 33 to 60 years, and it
      included 1,045 monozygotic and 1,899 dizygotic twin pairs. Questions on the
      frequency of sleepwalking were asked separately for occurrence in childhood and
      adulthood. Childhood sleepwalking was significantly more frequent in women
      ("often" in 2.8% of women and 2.0% of men and "sometimes" in 6.9% of women and
      5.7% of men). As adults, sleepwalking had occurred in 3.9% of men and in 3.1% of
      women, and it was reported "weekly" in 0.4% for both genders. There was no
      significant difference in frequency between monozygotic and dizygotic twin
      individuals, either in childhood or adulthood. For sleepwalking in childhood the
      probandwise concordance rate was 0.55 for monozygotic and 0.35 for dizygotic
      pairs, and for adults, 0.32 for monozygotic, and 0.06 for dizygotic pairs. Those
      who reported never having walked in their sleep in childhood did so as adults
      rarely (0.6%), both men and women. Those who reported walking in their sleep
      often or sometimes in childhood did so as adults for 24.6% of men and for 18.3%
      of women. Of adult men sleepwalkers 88.9% had a positive history of sleepwalking
      in childhood, and in women, 84.5%. The proportion of total phenotypic variance
      attributed to genetic influences was 66% in men and 57% in women in childhood
      sleepwalking, and 80% in men and 36% in women in adult sleepwalking. Our results
      show that there are substantial genetic effects in sleepwalking in both childhood
      and adulthood.

PMID- 9008516
TI  - Safety and efficacy of divalproex sodium monotherapy in partial epilepsy: a
      double-blind, concentration-response design clinical trial. Depakote Monotherapy
      for Partial Seizures Study Group.
AB  - This is the first randomized, double-blind, parallel-group, multicenter trial
      that evaluated the efficacy of divalproex sodium monotherapy by comparing seizure
      frequency in 143 patients with poorly controlled partial epilepsy randomly
      assigned to high (80 to 150 micrograms/mL; 555 to 1,040 mumol/L) or low (25 to 50
      micrograms/mL; 175 to 345 mumol/L) plasma valproate groups. There was a
      statistically significant reduction from baseline in the 8-week frequency of
      complex partial (p = 0.001) and secondarily generalized tonic-clonic seizures (p
      = 0.018) for patients in the high, compared with the low, plasma valproate group.
      Compared with baseline, there was a 30% median reduction in complex partial
      seizures for patients in the high group and a 19% increase for those in the low
      group. The median reduction for secondarily generalized tonic-clonic seizures was
      70% for patients in the high group compared with a 22% increase in the low group.
      Adverse events that occurred significantly more frequently in the high group
      included tremors, thrombocytopenia, alopecia, asthenia, diarrhea, vomiting, and
      anorexia. This study demonstrates the efficacy of divalproex sodium as
      monotherapy for the treatment of partial-onset seizures and supports its role as
      one of the first-line antiepileptic drug treatments for patients with partial
      epilepsy.

PMID- 9008517
TI  - Seizure symptomatology in infants with localization-related epilepsy.
AB  - The clinical characteristics of seizures in adults and children with localization
      related epilepsy have been clearly described and classified, but few data are
      available based on video EEG studies of postneonatal infants under 2 years of
      age. We analyzed 125 videotaped seizures from 23 infants aged 2 to 24 months with
      localization-related epilepsy defined by localized ictal EEG or localized lesion
      on neuroimaging with seizure-free surgical outcome. Seizure symptomatology was
      classified based on observable behavioral and motor manifestations and then
      correlated with location of the epileptogenic zone. Seizures characterized by
      decrease in behavioral motor activity with indeterminate level of consciousness
      and minimal or no automatisms ("hypomotor" seizures) arose from temporal,
      temporoparietal, or parieto-occipital regions (7 patients). Seizures with
      localized or bilateral clonic, tonic, or atonic motor phenomena arose
      predominantly from frontal, frontocentral, central, or frontoparietal areas (12
      patients). One patient had versive seizures arising from the contralateral
      occipital lobe, 2 patients had infantile spasms (one with a frontal tumor, one
      with temporo-parieto-occipital dysplasia), and one patient had unclassifiable
      seizures. Disruption of temporal or temporoparietal function resulted primarily
      in diminution of behavioral activity, whereas ictal activation of motor areas
      during frontal or central onset seizures resulted mainly in localized or
      generalized motor phenomena. Infantile spasms occurred because of lesions in
      either location. Using an approach based on easily observable behavioral and
      motor phenomena, it was possible to classify the seizures in all but one infant.

PMID- 9008518
TI  - Hypsarrhythmia: frequency of variant patterns and correlation with etiology and
      outcome.
AB  - To determine the frequency and significance of the EEG features of
      hypsarrhythmia, we analyzed the pre-ACTH records of 53 consecutive patients with
      infantile spasms for the severity of the following abnormalities: disorganization
      of background, slowing, high amplitude, spike activity, and for the presence or
      absence of each of the following patterns and variants: electrodecremental
      discharges, absence of normal sleep activity, relative normalization,
      hemihypsarrhythmia, burst suppression (BS), occipital hypsarrhythmia,
      interhemispheric asymmetry, and interhemispheric synchronization. We calculated a
      total score indicating the severity of the hypsarrhythmia for each record. The
      hypsarrhythmia variant patterns occurred frequently in up to 69% of the records.
      Patients with cerebral dysgenesis were more likely to have hemihypsarrhythmia or
      BS pattern persistent throughout the EEG. Patients with history of perinatal
      hypoxia-ischemia were more likely to have absence of normal sleep activity. The
      occurrence of each of the other variant patterns did not correlate with etiology.
      Favorable outcome did not correlate with the occurrence, or absence, of any of
      the variant patterns but was associated with faster background activity (< 75%
      delta), a lower total hypsarrhythmia score (< or = 10), and with absence of
      electrodecremental discharges on the pre-ACTH EEG. We conclude that variant
      patterns of hypsarrhythmia are frequent, generally do not correlate with
      prognosis, and thus are best included within the definition of hypsarrhythmia.
      The severity of the hypsarrhythmia, however, does have significant prognostic
      implications.

PMID- 9008520
TI  - A prospective study on the incidence and prognosis of Guillain-Barre syndrome in
      Emilia-Romagna region, Italy (1992-1993). Emilia-Romagna Study Group on Clinical
      and Epidemiological Problems in Neurology.
AB  - We performed a multicenter prospective study on the incidence and prognosis of
      Guillain-Barre syndrome (GBS) in the Emilia-Romagna region (3,909,512
      inhabitants), Italy, over a 2-year period (1992-1993). The case finding method
      was based on a surveillance system including neurologic departments, all private
      and public general hospitals, and all practicing neurologists. We also reviewed
      all the ICD codes of hospital discharges. Ninety-four patients with GBS were
      identified, giving a mean incidence rate of 1.20 per 100,000 per year. Men/women
      ratio was 1.94. Incidence rate increased with age for both sexes. There were no
      significant incidence variations among seasons or months. Antecedent infections
      were reported in 59% of the patients. There was an overall good prognosis. After
      6 months, 64% of patients had recovered and only 4% was still severely disabled.
      Acute mortality was 3%. Older age was the strongest predictor of poor outcome.

PMID- 9008521
TI  - Paraparesis due to syphilitic aortic dissection.
AB  - A patient is presented who developed an acute spinal cord infarct with
      paraparesis and segmental pain but no sensory or sphincter involvement.
      Investigations revealed an extensive dissecting thoracic aortic aneurysm and
      positive treponemal serologic findings consistent with tertiary cardiovascular
      syphilis.

PMID- 9008519
TI  - Epidemiology of multiple sclerosis in US veterans: VII. Risk factors for MS.
AB  - In previous papers of this series, we explored the epidemiology of MS, examining
      the effects of race, sex, geography, latitude and climate, migration, age at
      onset, population ancestry, and individual ethnicity on the risk of MS, using an
      unusually large cohort of MS cases and pre-illness matched controls comprising US
      veterans of World War II (WWII) and the Korean Conflict (KC). In this paper, we
      examine primarily the effect of other factors on the risk of MS in this cohort
      and their relation to those previously studied. We found here that latitude tier
      of residence at entry into active duty (EAD), years of education, and
      socioeconomic class (coded from occupation) were similarly associated with MS
      risk among white men, black men, and white women. Higher levels of each factor
      showed increased MS risk. Multivariate analyses indicated that for white male
      WWII subjects an urban address, 9 or more years of education, uncorrected visual
      acuity less than 20/20 at EAD, a more northern latitude, and a higher proportion
      of the subject's EAD state population reporting Swedish ancestry each
      significantly increased the risk of MS. White male KC subjects showed roughly the
      same patterns, except that uncorrected visual acuity less than 20/20 was
      associated with lower MS risk (ancestry/ethnicity was not studied). For black
      male WWII and KC subjects combined, a similar analysis (omitting
      ancestry/ethnicity) showed that only latitude at EAD and 9 or more years of
      education were independently associated with a significantly higher MS risk, and
      for WWII plus KC white women (also without ancestry/ethnicity), only latitude was
      a significant risk factor in these multivariate analyses. The smaller number of
      subjects, especially in these last two groups, limited the power to detect
      statistically significant risks in these last analyses. Similarities to white men
      of WWII in univariate analyses for all other groups suggest that findings for the
      former would otherwise apply to the latter. Although the interpretations of these
      associations may be obscure, in addition to geography, age, sex, and race, per
      se, higher socioeconomic status is significantly associated with higher MS risk
      in black and white men and in white women in the United States.

PMID- 9008522
TI  - HIV infection and cognition in intravenous drug users: long-term follow-up.
AB  - A cohort of 185 HIV-infected injection drug users (IDUs) and seronegative
      controls was followed with semiannual neuropsychological assessments for up to
      4.5 years. Changes in cognitive performance over time were evaluated, and results
      of seronegative controls were used to adjust for level of education and practice
      effects. The effects of duration of follow-up, decline in CD4+ count, development
      of clinical symptoms, antiretroviral use, and diagnosis of AIDS on changes in
      neuropsychological performance over time were assessed with regression models
      using the generalized estimating equation approach. Improvement in performance
      over time, consistent with practice effects, was observed for all measures. The
      only subtest for which the magnitude of the practice effects was mildly
      attenuated relative to the seronegative controls was Grooved Pegboard, dominant
      hand. After adjusting for disease progression and antiretroviral therapy use,
      none of the time trends for the neuropsychological test scores were significant,
      suggesting no decline in performance of the seropositive patients relative to the
      seronegative controls. With development of clinical symptoms, there was a trend
      in the direction of declining performance. For subjects reporting two or more
      symptoms but not using antiretroviral therapy, the trend was not significant,
      whereas having two or more symptoms and using antiretroviral therapy was
      associated with significantly worse performance on tests of psychomotor speed and
      memory. With development of AIDS, a significant decline in performance was
      observed on measures of motor and psychomotor speed as well as memory. There is
      thus no evidence to suggest that HIV infection in the context of chronic drug and
      alcohol use significantly alters the frequency or rate of progression of
      cognitive symptoms. These findings suggest that the natural history of cognitive
      changes secondary to HIV infection is similar among HIV-infected IDUs and other
      risk groups such as homosexual/bisexual men.

PMID- 9008523
TI  - Fixation-off-sensitive epilepsy with absences and absence status: video-EEG
      documentation.
AB  - A 33-year-old woman of borderline normal intelligence had catamenial absence
      status epilepticus and absences since early teens, diagnosed as temporal lobe
      epilepsy. Clinical and video-EEG evaluation documented that she suffers from a
      rare epileptic condition manifested with fixation-off sensitivity, absences,
      absence status, and infrequent generalized tonic-clonic seizures.

PMID- 9008524
TI  - Spatial bias: attentional and intentional influence in normal subjects.
AB  - Normal subjects often demonstrate a spatial bias on line bisection (LB) and
      cancellation (CA) tasks. We wanted to learn if horizontal spatial bias found in
      normal subjects may be dissociable into sensory-attentional (ATT) and motor
      intentional (INT) subgroups similar to those described in brain-injured patients
      with spatial neglect. We studied the influence of ATT and INT factors on the
      spatial bias observed in normal subjects using a new technique that uncouples the
      direction of action from the direction of attention. This technique also allowed
      us to test both LB and CA tasks on the same individuals. Our results show that
      ATT bias significantly influenced performance on an LB task, whereas performance
      on a CA task was influenced by biases in both the ATT and INT systems. In
      addition, the overall bias on these two tasks reflects an interaction between the
      biases induced by the ATT and INT systems that may be in the same or different
      directions.

PMID- 9008525
TI  - Serum IgM monoclonal autoantibody binding to the 301 to 314 amino acid epitope of
      beta-tubulin: clinical association with slowly progressive demyelinating
      polyneuropathy.
AB  - We identified five patients with IgM monoclonal autoantibodies that bound to
      human brain tubulin. In a companion study, we found that IgM in these sera
      selectively recognized one of three epitopes on tubulin. IgM from three patients
      bound selectively to a small epitope on human beta-tubulin comprising amino acids
      301 to 314. The other two sera recognized tubulin amino acids 215 to 235 and 315
      to 336. In this study, we compared the clinical syndromes in these patients with
      the tubulin epitope recognized by their serum IgM. The three patients with IgM
      binding to tubulin amino acids 301 to 314 all had chronic inflammatory
      demyelinating polyneuropathy (CIDP) syndromes with slowly progressive weakness,
      hyporeflexia, and electrophysiologic studies consistent with demyelination. Two
      of these patients had significant asymmetry to their weakness. The two other
      patients had diagnoses of polyradiculopathy and amyotrophic lateral sclerosis
      with no evidence of peripheral nerve demyelination. We conclude that IgM
      monoclonal anti-tubulin antibodies have some association with demyelinating
      polyneuropathy syndromes, but may occur in patients with other clinical syndromes
      as well. A stronger association with demyelinating polyneuropathies may occur if
      the anti-tubulin antibodies recognize the 301 to 314 amino acid epitope on
      tubulin. This tubulin epitope, or a similar one on another molecule, could play
      an important antigenic role in the development of demyelinating polyneuropathies
      with features of CIDP.

PMID- 9008526
TI  - Reconstituted botulinum toxin type A does not lose potency in humans if it is
      refrozen or refrigerated for 2 weeks before use.
AB  - Botulinum toxin type A (BTX-A) (Botox, Allergan, Irvine, CA) labeling recommends
      its use within 4 hours of reconstitution. Since BTX-A is available only in 100
      unit vials, a substantial quantity is often discarded. Using eight volunteers, we
      measured the percent decline in extensor digitorum brevis (EDB) M-wave amplitude
      (percent paralysis) following injection of freshly reconstituted BTX (right EDB)
      and compared this with the decline following injection of BTX that was refrozen (
      20 degrees C) or refrigerated (+4 degrees C) for 2 weeks (left EDB) after
      reconstitution. When analyzed as paired data, there was essentially no difference
      in the muscle paralysis resulting from fresh BTX compared with refrozen or
      refrigerated BTX, and no statistical difference between groups was noted.
      Reconstituted BTX-A that is subsequently refrigerated or refrozen for 2 weeks
      does not lose potency in humans.

PMID- 9008527
TI  - Autosomal dominant hyaline body myopathy presenting as scapuloperoneal syndrome:
      clinical features and muscle pathology.
AB  - Hyaline bodies are rare subsarcolemmal aggregates in type 1 fibers of the
      skeletal muscle, stain pale pink with hematoxylin-eosin and pale green with the
      modified Gomori trichrome, and lack reactivity for glycogen and oxidative
      enzymes. We report clinical findings of autosomal-dominant hyaline body myopathy
      in seven members in four generations and muscle biopsy findings in two of them.
      Slowly progressive muscle weakness and atrophy developed with scapuloperoneal
      distribution; age at onset was from the first to the fifth decade. Muscle biopsy
      showed subsarcolemmal hyaline bodies in approximately 20% of type 1 fibers.
      Hyaline bodies showed myofibrillar ATPase activity after acid pre-incubation.
      Immunohistochemically, they stained intensely with myosin heavy chain (slow), but
      not with myosin heavy chain (fast). Ultrastructurally, they consisted of granules
      sometimes in linear array, filaments, and amorphous materials. These findings
      suggest that hyaline bodies may be products of degeneration of myosin heavy chain
      (slow).

PMID- 9008529
TI  - Successful treatment of persistent migraine aura with divalproex sodium.

PMID- 9008528
TI  - A novel mutation in the sterol 27-hydroxylase gene of a Pakistani family with
      autosomal recessive cerebrotendinous xanthomatosis.
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of
      lipid storage with prominent neurologic features. The disease is associated with
      mutations in CYP27, which encodes mitochondrial sterol 27-hydroxylase, an enzyme
      that catalyzes the oxidation of sterol intermediates during bile acid synthesis.
      The loss of this enzyme results in accumulation of cholestanol in the nervous
      system and other tissues. Six different mutations have been previously described
      in CTX. We analyzed a Pakistani family, which included four affected individuals
      with clinical characteristics of CTX, for mutations in CYP27. The exons of CYP27
      in the family DNA were amplified by polymerase chain reaction (PCR) and analyzed
      for mutations by band shifts (single stranded conformational polymorphism [SSCP])
      and DNA sequencing. The PCR product for exon 4 showed an SSCP change in this
      family. The DNA of affected individuals showed an abnormal mobility pattern
      interpreted as homozygous for the mutation. One non-affected sibling was
      homozygous for the normal migrating pattern, whereas the parents and another non
      affected sibling were heterozygous. The sequence of exon 4 of affected
      individuals showed a substitution of C to T in codon 237, thus substituting
      arginine to a stop codon. This mutation would terminate the translation, which
      may result in a protein half the size of the wild type rendering it practically
      inactive.

PMID- 9008530
TI  - Meningeal involvement in Wegener's granulomatosis confirmed and monitored by
      positive circulating antineutrophil cytoplasm in cerebrospinal fluid.
AB  - MRI and CSF investigations revealed meningeal involvement in a 29-year-old
      patient with biopsy-confirmed Wegener's granulomatosis. The intracranial
      manifestation of Wegener's granulomatosis was supported by the detection of
      pathologic circulating antineutrophil cytoplasm (c-ANCA) in the CSF. We monitored
      disease activity by c-ANCA measurement in the CSF. After repeated cycles of
      intrathecal administration of methotrexate and corticoids, progression of
      meningeal infiltration stopped, and CSF c-ANCA titers became negative.

PMID- 9008531
TI  - Isolated meningeal vasculopathy associated with Clostridium septicum infection.
AB  - A 28-year-old patient with acute lymphoblastic leukemia and neutropenia developed
      necrotizing enterocolitis and Clostridium septicum bacteremia, followed by
      rhabdomyolysis, skin rash, and acute neurologic changes. Numerous cortical
      leptomeningeal enhancements were present on head MRI. Meningeal and brain biopsy
      showed segmental, full-thickness lysis of smooth muscle cells of medium-sized
      meningeal vessels with overall preservation of the structure of the vessel wall.

PMID- 9008532
TI  - Cyclin-dependent kinase 5 in Lewy body-like inclusions in anterior horn cells of
      a patient with sporadic amyotrophic lateral sclerosis.
AB  - Lewy body-like inclusion (LI) is a cytoplasmic inclusion body deposited in
      anterior horn cells of patients with amyotrophic lateral sclerosis (ALS), in
      which there are phosphorylated neurofilament proteins (NFP). Since
      phosphorylation of NFP occurs normally in the axon, aberrant phosphorylation of
      NFP should take place in these cell bodies. To clarify the mechanism of LI
      formation it is crucial to identify the kinase responsible for the
      phosphorylation. We found cyclin-dependent kinase 5 (cdk5) immunoreactivity in
      most of LI in an ALS patient. Since cdk5 phosphorylates NFP, cdk5 is a candidate
      kinase for NFP in LI and might be involved in the cytoskeletal disorganization in
      LI-containing neurons.

PMID- 9008533
TI  - MRI and brainstem auditory evoked potential evidence of eighth cranial nerve
      involvement in multiple sclerosis.
AB  - An MS patient experienced sudden hearing loss. Brainstem auditory evoked
      potentials, previously normal, showed substantial abnormalities that suggested
      the impairment of the distal part of the acoustic nerve. MRI detected a small
      hyperintense lesion along the acoustic nerve; the lesion decreased in size and
      then disappeared after steroid treatment. This demonstrates that a demyelinating
      lesion in the distal tract of the eighth cranial nerve may cause an acute hearing
      loss in MS.

PMID- 9008534
TI  - Hereditary ataxia with sensory neuronopathy: Biemond's ataxia.
AB  - We report the case of a man with late-onset hereditary ataxia and sensory loss.
      Three of his sisters were affected by a similar disorder; to date no other
      members of his family have developed symptoms. The clinical features of this
      family are similar to a rare form of autosomal dominant hereditary ataxia,
      recently classified as SCA4. Postmortem findings indicate that this syndrome is
      marked by degeneration of cerebellar Purkinje cells, dorsal root sensory ganglion
      neurons, and the ascending posterior columns. Similar clinical and pathologic
      findings were reported by Biemond in 1954.

PMID- 9008536
TI  - Multiple brain gas embolism after ingestion of concentrated hydrogen peroxide.
AB  - We present a 63-year-old man who developed multiple brain infarction after
      ingesting a 35% hydrogen peroxide solution. Neurologic examination revealed left
      hemiparesis, primarily affecting the lower limb, and mild weakness of the right
      lower limb. Gadolinium-enhanced MRI revealed patchy bilateral brain lesions.
      Oxygen gas embolization is the likely cause of the brain infarctions.

PMID- 9008535
TI  - Gluteal compartment syndrome due to rhabdomyolysis after heroin abuse.
AB  - We report a 30-year-old man who developed painful swelling of his right leg and
      complete sciatic nerve palsy after an i.v. injection of heroin. Excessive
      elevation of serum creatine phosphokinase indicated the presence of
      rhabdomyolysis. Fasciotomy of the gluteus maximus led to rapid and complete
      recovery from sciatic nerve palsy. Nontraumatic rhabdomyolysis may cause a
      gluteal compartment syndrome that requires immediate fasciotomy.

PMID- 9008537
TI  - Unusual MRI and pathologic findings of progressive multifocal leukoencephalopathy
      complicating adult Wiskott-Aldrich syndrome.
AB  - We present a long-surviving patient with Wiskott-Aldrich syndrome complicated by
      atypical progressive multifocal leukoencephalopathy (PML). MRI showed multiple
      tiny spots of Gd-DTPA-enhanced lesions on the T1-weighted image. Pathologic
      findings for brain biopsy were patchy demyelinated vascularized lesions
      infiltrated by a surprising number of eosinophils. The presence of polyomavirus
      JC was confirmed by in situ hybridization and polymerase chain reaction. PML
      should be included in the differential diagnosis when Gd-DTPA-enhanced spotty
      lesions are present in the white matter, especially in patients who have a mild
      immunologic defect.

PMID- 9008538
TI  - Mutations in the proteolipid protein gene in Japanese families with Pelizaeus
      Merzbacher disease.
AB  - Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelinating disorder of
      the CNS resulting from abnormalities in the proteolipid protein (PLP) gene.
      Exonic mutations in the PLP gene are present in 10 to 25% of all cases. In
      investigating genotype-phenotype correlations, we screened five Japanese families
      with PMD for PLP gene mutations and compared their clinical manifestations. We
      identified two novel nucleotide substitutions in exon 5, at V208N and at P210L,
      in two families. In the remaining three families, there were no mutations
      detected. Although all patients satisfied the criteria for the classical form of
      PMD, two families not carrying the mutations showed milder clinical
      manifestations than those with the mutations. Since linkage analysis has shown
      homogeneity at the PLP locus in patients with PMD, our findings suggest that
      there may be genetic abnormalities other than exonic mutations that cause milder
      forms of PMD.

PMID- 9008539
TI  - MRI-based hippocampal volumetry and T2 relaxometry: correlation to verbal memory
      performance in newly diagnosed epilepsy patients with left-sided temporal lobe
      focus.

PMID- 9008541
TI  - Needle cervical root stimulation may be complicated by pneumothorax.

PMID- 9008540
TI  - Demyelinating brachial neuropathy complicating syngeneic graft-versus-host
      disease.

PMID- 9008542
TI  - Meeting badge neuropathy.

PMID- 9008543
TI  - Amyloid angiopathy.

PMID- 9008544
TI  - Amyloid angiopathy.

PMID- 9008545
TI  - Failure to recall.

PMID- 9008546
TI  - Failure to recall.

PMID- 9008547
TI  - Epidural anesthesia.

PMID- 9008548
TI  - Epidural anesthesia.

PMID- 9008549
TI  - Epidural anesthesia.

PMID- 9008550
TI  - Cobalamine deficiency.

PMID- 9008552
TI  - Cervical radiculopathies.

PMID- 9008551
TI  - Cobalamine deficiency.

PMID- 9008553
TI  - Hemorrhagic infarct.

PMID- 9008555
TI  - Crisis in medical research.

PMID- 9008556
TI  - The importance of feedback training.

PMID- 9008554
TI  - Cyclosporine mutism.

PMID- 9008557
TI  - Training residents to comply with colorectal-cancer screening guidelines.

PMID- 9008558
TI  - Fostering faculty mentorship of junior medical students.

PMID- 9008559
TI  - Leaving the cloister but keeping the faith.

PMID- 9008560
TI  - When patients feel ignored: study findings about medical liability.

PMID- 9008561
TI  - Defensible assessment of the competency of the practicing physician.
AB  - When a physician's license to practice is at stake, professional acceptance and
      legal challenge are concerns for an organization undertaking competency
      assessments for practicing physicians. In 1995 the Physician Review and
      Enhancement Program (PREP), a program of McMaster University sponsored by the
      College of Physicians and Surgeons of Ontario, underwent an external review by
      evaluation experts. As a result, one of the four assessment tools, the Structured
      Office Oral, was dropped, as it was insufficiently structured to be reliable and
      because it did not add significantly to the other tools. The content of all
      assessment tools was revised based on a PREP-developed blueprint for family
      practice. The multiple-choice questions (MCQs) were upgraded through
      collaboration with Canada's physician-accrediting body, the Medical Council of
      Canada (MCC), by the physician assessors, who chose MCQs according to the
      blueprint from the MCC question bank. The standardized-patient assessment was
      also refined by these physicians, who developed scenarios of standardized
      clinical cases with predefined performance criteria. Finally, through
      collaboration with the American Board of Emergency Medicine, a chart-stimulated
      recall test, in which the physician's own patient records are used to assess the
      physician's practice behavior, was restructured to ensure objectivity in
      standardization and interpretation. The result of these changes in the assessment
      tools is a more standardized and structured program of assessing physicians'
      competencies.

PMID- 9008562
TI  - Are the recommendations of the AAMC's task force on the generalist physician
      still valid?
AB  - A few years ago, most opinion leaders and workforce analysts believed that the
      number of generalist physicians in the United States was much too low. The AAMC
      responded to this concern by convening a task force to review the evidence
      bearing on the U.S. supply of generalist physicians and to make recommendations
      for action by the AAMC and its member institutions. In 1992, the task force
      called for at least half the graduates of U.S. allopathic medical schools to
      enter practice as generalists and for medical schools to design their educational
      programs to promote an affinity for generalism among their students. Since that
      time, however, research findings have suggested that the current size of the
      country's generalist physician workforce in relation to projected need may indeed
      be adequate. In light of these recent observations, the authors asked whether the
      task force's major recommendations remain valid. In this article, they state
      their reasons for thinking that it definitely does. After reviewing the recent
      research findings mentioned above, the authors show that simply to maintain the
      current size of the generalist physician workforce, a marked increase will be
      needed in the number of U.S. medical school graduates who choose to become
      generalists. In the aggregate, this amounts to roughly half the graduating
      classes of LCME-accredited medical schools, as called for by the AAMC in 1992.
      (The authors predict that international medical graduates will not make up a
      significant percentage of the country's generalist workforce, and that U.S.
      medical school graduates will be the predominant source of these physicians in
      the future.) Equally important, the new educational approaches being created by
      medical schools to embed generalism in their curricula are necessary to ensure
      that all graduates, regardless of their specialty choices, be well grounded in
      the principles and skills of "general physicians" so they can function well in
      the new health care system that is rapidly evolving.

PMID- 9008563
TI  - Graduates of foreign medical schools: progression to certification by the
      Educational Commission for Foreign Medical Graduates.
AB  - The application process leading to certification by the Education Commission for
      Foreign Medical Graduates (ECFMG) was studied using the group of 9,491 graduates
      of foreign medical schools who initiated their applications in 1988. Using the
      ECFMG's database, these applicants' countries of citizenship, examination
      histories, certification status, and exchange visitor status were determined for
      a period of seven years and 9 months, ending in September 1995. Within that time,
      45% of these applicants became ECFMG-certified, and 26% of that group entered
      residency programs accredited by the Accreditation Council for Graduate Medical
      Education. Of the total number of non-U.S. citizens (2,243) who entered such
      programs, 61% did so as exchange visitor physicians. The remainder had other
      kinds of visa status, such as permanent resident, or had become U.S. citizens.
      Although U.S. citizens and non-U.S. citizens achieved certification at the same
      rate (45%), the U.S. citizens had greater success in obtaining positions in
      graduate medical education (GME). Seventy-four percent of the ECFMG-certified
      certified U.S. citizens entered GME, versus 57% of the ECFMG-certified non-U.S.
      citizens. The status of the 55% of the 9,491 applicants who did not obtain
      certification is discussed; a portion of this group of this group continues to
      pursue certification. Details and requirements of the ECFMG certification process
      are also described.

PMID- 9008564
TI  - The salary responsibility program for full-time faculty members in an academic
      clinical department.
AB  - The authors report a system developed in the Department of Medicine of the
      University of Maryland School of Medicine to encourage members of the full-time
      faculty to assume greater responsibility for their compensation. A member of the
      department's administrative staff individually interviews each faculty member and
      fills out, with the member, a "scorecard" that contains the number of hours per
      month and per year that the member reports were spent on his or her duties--such
      as teaching, attending, and consulting--that are assigned by the department or
      its divisions. This report also contains the record of unassigned time devoted to
      research (for investigators) or to personal practice (for clinicians). Assigned
      duties includes the time spent by clinicians performing procedures such as
      bronchoscopy cardiac catheterization, and endoscopy. The department pays for the
      otherwise unsupported costs of salary and benefits associated with assigned
      duties, and the faculty member is responsible for part of his or her compensation
      for time spent in research or practice. The program was developed and the data
      collected during the summer and fall of 1995. The salary reductions were applied
      on July 1, 1996. During the 1996-97 academic year the department projects a
      savings of $110,362 from compensation withheld from faculty members unable to
      fulfill their salary responsibilities and not paid to members who left the
      department, in part because of expected reductions in their incomes. The program
      has stimulated other faculty members to develop salary support with even greater
      vigor than that might otherwise have shown.

PMID- 9008565
TI  - The roles of experience and reflection in ambulatory care education.
AB  - While ambulatory care education typically does not provide much direct
      instruction, supervision, or feedback, experiential learning occurs. Using
      experiential learning theory, the authors describe how this process of learning
      works. the process is characterized by a cycle of having a concrete experience
      (e.g., an encounter with a patient), reflecting on that experience as it unfolds,
      formulating conceptualizations and generalizations from the experience, and
      testing those generalizations and concepts in other situations. With this model
      in mind, the authors make four recommendations for improving ambulatory care
      education for both medical students and residents: (1) plan for experiences in
      carefully selected ambulatory care settings; (2) facilitate reflective
      observation; (3) encourage conceptual thinking and inquiry; and (4) promote
      feedback and testing of insights from experiences. The authors discuss the
      rationale behind each recommendation and offer guidelines for how each might be
      implemented.

PMID- 9008566
TI  - Re-imagining the medical informatics curriculum.
AB  - Most physicians in academics, administration, and private practice are
      insufficiently trained to cope with the current challenges facing medicine.
      Although information technology, and medical informatics in particular, has been
      considered to be part of the solution to this problem, the philosophical
      underpinnings of informatics remain a source of much discussion. Too often, new
      technology is seen as a new way to do the same things, rather than as an
      opportunity for a radical reenvisioning of the processes and practices
      themselves. As a consequence, practitioners and educators fail to make the best
      uses of new technologies, and fail to offer medical students the comprehensive
      training in medical informatics that they will need as they move into the real
      worlds of practice and academics. In this paper, the author describes an
      imaginary informatics curriculum made up of six core courses: Introduction to
      Complexity, Decisions and Outcomes, Scarcity and Conflict, Teamwork and
      Organizations, Representing Knowledge and Action, and Groupware and
      Collaboration. He does not recommend that these hypothetical courses actually be
      implemented, but presents them in the hope that they may serve as a starting
      point for discussions of how informatics can be incorporated into the curriculum
      in a more substantive way.

PMID- 9008567
TI  - Ensuring students' well-being as they learn to support victims of violence.

PMID- 9008568
TI  - First-year medical students' knowledge of, attitudes toward, and personal
      histories of family violence.
AB  - PURPOSE: To assess first-year students' knowledge of, attitudes toward, and
      personal histories of family violence. METHOD: An anonymous, self-administered,
      70-item questionnaire was developed and distributed in the first six months of
      medical school to 390 first-year students at three New England medical schools in
      1991-92. The students were tested on knowledge and asked questions about their
      personal histories. Attitude questions were scored on a five-point Likert scale.
      Attitude scales were developed by dividing questions into three content groups
      (education about family violence, the physician as advocate, acceptability of
      violent behaviors) and removing items for which inter-item coefficients with all
      other items were less than .20. Two-tailed t-tests were performed on continuous
      variables and chi-square tests on categorical variables. Ninety-five percent Cls
      were calculated for point estimates. RESULTS: In all, 370 students (95%)
      responded. Of these, 139 (38%) reported personal histories of abuse. The mean
      knowledge score was 11.3 (of 16 questions). One-third of the students answered
      more than 75% of these questions correctly; 12% answered less than half of the
      questions correctly. The women felt more strongly than the men about the need for
      violence education (p < .001). The students who reported histories of abuse more
      strongly favored education (p < .05) and advocacy roles (p < .001) for
      physicians. In addition, the students who had histories of family violence were
      more likely to report histories of suicidal thoughts (p < .0001). CONCLUSION: The
      students lacked knowledge but felt a need to learn more about family violence.
      Family violence curricula should be better integrated into medical education.
      These curricula should be sensitive to students' attitudes, given the reported
      high prevalence of personal histories of family violence among students.

PMID- 9008569
TI  - Primary care physicians' recognition of and attitudes toward domestic violence.
AB  - PURPOSE: Physicians fail to identify the majority of domestic violence victims,
      even though they are often the first and only individuals to whom a victim may
      present. The present study was designed to assess primary care physicians'
      recognition of and attitudes toward domestic violence. METHOD: Of the 148 primary
      care physicians in three midwestern counties, all the women and a random sample
      of the men were included in the survey, for a total of 83. A seven-page
      questionnaire was developed that contained items about demographics and practice
      characteristics, and questions about the following aspects of domestic violence:
      knowledge, attitudes, importance, and prevalence in practice; attitudes toward
      responsibility; current practices and protocols used; level of education and
      domestic violence received; and opinions on how best to distribute information
      and/or education concerning domestic violence. The questionnaire was mailed in
      1994. Follow-up was conducted through phone calls, remailings, and visits to the
      physicians' offices. Responses were examined using chi-square tests and two
      tailed t-tests. RESULTS: The response rate was 63% (52 of 83); 53% of those
      responding were family physicians and 47% were general internists; 34% were
      women. Although all of the physicians agreed that finding and treating domestic
      violence is important, less than half agreed that domestic violence was a
      significant problem in their patient populations. Almost 96% of the physicians
      believed that more should be done to educate physicians about domestic violence,
      and 94% agreed that domestic violence should be included in a doctor's
      professional medical training; yet nearly half said they would not participate in
      a domestic violence forum. Even though 41% noted that they had received some type
      of formal education about domestic violence, 57% felt that their medical
      education had inadequately prepared them to deal with domestic violence, and less
      than 25% reported that they had been trained to diagnose domestic violence. The
      family physicians and the female physicians had received more education about
      domestic violence and were more comfortable addressing domestic-violence
      situations. The older physicians were less comfortable addressing domestic
      violence and were less likely to agree that education about domestic violence
      should be a part of medical training. CONCLUSION: Interventions by the medical
      community to increase physician awareness of domestic violence and available
      treatment resources are necessary, and domestic-violence information should be
      included in formal medical curricula.

PMID- 9008570
TI  - A survey of family-violence curricula in Virginia medical schools and residencies
      at university medical centers.
AB  - PURPOSE: To examine the status (as of 1995) of family violence curricula at
      Virginia's three medical schools and their affiliated residencies. METHOD:
      Questionnaires were sent in the fall of 1995 to the deans of undergraduate
      medical education at the three schools and the directors of the 69 fully
      accredited residencies at the university medical center. The questionnaires
      inquired about the presence of particular family-violence topics in the curricula
      (battered women, child abuse, elder abuse) and whether teaching about family
      violence was required or elective. In addition, the medical schools' departments
      were asked to identify faculty who were experts in the area of family violence.
      RESULTS: All three schools responded about undergraduate education, showing
      considerable variability among departments concerning whether instruction was
      required or elective and what instructional methods were used. A total of 48
      (70%) of the 69 residencies responded. Twenty-six (54%) indicated that they had
      at least some curriculum content related to particular family-violence topics:
      child abuse, 20 (42%); battered women, 13 (27%); and elder abuse, nine (19%). A
      total of 27 faculty with expertise in family violence were identified, and 16
      were experts in identifying and treating injuries related to family violence. No
      expert was identified in such areas as mental health sequelae or violence
      prevention. CONCLUSION: The results allowed for the development of
      recommendations regarding medical education about family violence in Virginia,
      including the formal integration of family-violence curricula into medical school
      and internship and residency programs, and the coordination of disciplines within
      Virginia in family-violence prevention.

PMID- 9008571
TI  - The effect of medical education on students' patient-satisfaction ratings.
AB  - PURPOSE: To determine whether medical students' interpersonal and communication
      skills, as measured by satisfaction ratings given by standardized patients (SPs),
      improves or deteriorates with additional training and experience. METHOD: A
      longitudinal study was made of a single cohort of 133 medical students scheduled
      to graduate in 1994 from the University of Illinois College of Medicine at
      Chicago. Clinical performance examinations employing clinical encounters with SPs
      were given at the end of the students' second year at the end of the first
      quarter of their fourth year. The second-year examination consisted of four
      student-SP encounters for each student; the fourth-year examination consisted of
      16 such encounters. For each examination, SP perceptions of interpersonal and
      communication skills were measured using six items from the American Board of
      Internal Medicine Patient Satisfaction Questionnaire; the items employed five
      ordinal-scale descriptors (from 1 = poor to 5 = excellent). The unit of analysis
      was the student-SP encounter. For each year, ratings on each item were averaged
      across encounters to produce a mean rating for each item; in addition, ratings
      across all the encounters and items were averaged to produce a mean total patient
      satisfaction rating. The percentage of fail or poor ratings given for each item
      was calculated, as was the average of these percentages across the items. All
      rating calculations were done between years and between genders. Two-tailed,
      paired t-tests and F-ratios were used for comparisons between years and between
      genders, respectively. Finally, ratings for a comparison group of first-, second
      , and third-year internal medicine residents were gathered under similar testing
      conditions. RESULTS: Mean total patient satisfaction with the students' clinical
      performances improved from the first examination (3.51, SD, .84) to the second
      (3.60, SD, .86). The percentage of student encounters receiving fair or poor
      ratings decreased from 14.5% in the second year to 12% in the fourth year;
      resident encounters received a fair or poor rating 7.8% of the time. The female
      students received fewer fair or poor ratings than did the male students both in
      their second year (11.7% vs 16%) and in their fourth year (9.3% vs 12.8%). Of the
      six patient-satisfaction items, both the students and the residents consistently
      were ranked lowest in encouraging patients to ask questions and answering patient
      questions. CONCLUSION: Contrary to the stated beliefs of some physician-educators
      that students' skills deteriorate during the course of training, these medical
      students' interpersonal and communication skills improved with additional
      training and experience.

PMID- 9008572
TI  - A cost analysis of an introduction to clinical medicine course in a non
      university teaching hospital.
AB  - PURPOSE: To determine the major direct costs associated with teaching the
      Introduction to Clinical Medicine (ICM) course at a non-university teaching
      hospital. METHOD: The major direct costs were calculated for ICM, a ten-week
      course taught at the Columbia Michael Reese Hospital and Medical Center, a non
      university teaching hospital, to second-year students from the University of
      Illinois College of Medicine at Chicago. The major components of ICM are physical
      diagnosis, clinical pathology, and radiology, as well as some pediatrics; the
      bulk of the costs for these components is incurred for physician staff time.
      Physician time was reported by component coordinators, who also estimated
      preparation and teaching times. Physician cost per hour was chosen as that
      equivalent to assistant professors' salaries. Resident cost per hour was
      determined from the average resident salary at the hospital. Miscellaneous direct
      costs (of basic life-support certification, gift certificates, and standardized
      patients) were calculated from the receipts and bills submitted for payment. In
      the spring of 1995 the hospital conducted ICM for 26 students. RESULTS: The
      attending physicians worked a total of 736.5 hours, for a cost of $37,303. The
      residents worked a total of 314 hours, for a cost of $4,396. Miscellaneous costs
      totaled $2,019. The total of these major direct costs was $43,718, or $1,681 per
      student. CONCLUSION: These results can help medical educators and policymakers as
      they investigate innovative teaching methods and funding sources.

PMID- 9008573
TI  - Career choices among Saudi medical students.
AB  - PURPOSE: To identify the career choices, intended practice locations, and reasons
      for career choices of final-year Saudi medical students. METHOD: A total of 302
      final-year students at the four Saudi medical colleges were asked to complete a
      self-report questionnaire at the end of the 1994 academic year. RESULTS: A total
      of 253 students (84%) responded (149 men and 104 women). The most frequently
      chosen specialties were internal medicine (17%), surgery (16%), pediatrics (14%),
      and obstetrics-gynecology (11%). Twenty-seven percent were not sure of their
      future career choices. More of the men chose surgery, but more of the women chose
      obstetrics-gynecology and ophthalmology. The leading reasons for selecting a
      specialty were "personal interest," "a chance to help people," "availability of
      postgraduate training," "few specialists in the country," and "prestige." The
      most frequently chosen locations for postgraduate training were Saudi Arabia
      (56%) and Canada (40%). The qualifying examinations the students wished to pass
      were mostly the Canadian boards (49%) and the Arab boards (48%). A majority
      intended to practice in hospitals (90%) and in cities (85%). CONCLUSION: The
      small proportions of students who chose family medicine and some other
      specialties indicate that the current drastic deficiency of trained Saudi primary
      health care physicians will continue unless targeted strategies to produce more
      of these physicians are undertaken.

PMID- 9008574
TI  - Influence of gender on specialty choices in a Brazilian medical school.
AB  - PURPOSE: To examine the influence of gender on the specialty choices of graduates
      from a Brazilian medical school. METHOD: Data for graduates of the Faculty of
      Medicine of Ribeirao Preto, University of Sao Paulo (FMRP-USP) who enrolled in
      the FMRP-USP's residency program were pooled for surgery, internal medicine,
      pediatrics, obstetrics-gynecology, anesthesiology, ophthalmology, radiology, and
      orthopedics and were analyzed by gender in two periods, 1979-1984 (n = 414) and
      1989-1994 (n = 407). The data were analyzed statistically by the chi-square test
      and Fisher's exact probability test. RESULTS: Women predominated in pediatrics
      and men in surgery and orthopedics in both periods, with no predominance of
      either gender in the other specialties. Between the two study periods, there were
      decreases in the choices of both genders for internal medicine and increases in
      the choices of the men for anesthesiology and of the women for radiology.
      CONCLUSION: Significant changes occurred in the pattern of specialty choices
      between the men and the women and the two study periods. Considering the needs of
      the Brazilian health care system, the trends in career choices and the influence
      of gender should be continuously scrutinized.

PMID- 9008575
TI  - Residents' question-asking behaviors during work rounds.

PMID- 9008577
TI  - Simulated patients in an electronic patient record.

PMID- 9008576
TI  - An advanced physical diagnosis course for internal medicine residents.

PMID- 9008578
TI  - Premedical course recommendations of premedical advisers, medical students, and
      medical school faculty.

PMID- 9008579
TI  - Use of a non-monetary incentive to improve physician responses to a mail survey.

PMID- 9008580
TI  - Comparing two formats for clinical "pearls" at morning report.

PMID- 9008581
TI  - Family violence: an overview.
AB  - This article reviews the definitions and epidemiology of the several forms of
      interpersonal violence in family and intimate relationships. Interpersonal
      violence includes both fatal and nonfatal violence where physical force, or other
      means, is used by one person with the intent of causing harm, injury, or death:
      family violence includes child maltreatment, adult intimate-partner violence, and
      elder mistreatment; abuse refers to a pattern of behaviors organized around the
      international use of power by one person to control another; and child
      maltreatment involves the abrogation of adult responsibilities for the care and
      protection of children, and includes child abuse, child sexual abuse, and child
      neglect. Violence is a major public health problem in the United States. Half of
      assault and homicide victims are related to or acquainted with their assailants,
      as are two-thirds of rape victims. Children and adolescents are at particular
      risk of violence. The study of interpersonal violence is a complex and evolving
      held, and is increasingly a part of training and medical practice in academic
      settings.

PMID- 9008582
TI  - A medical student's perspective on education about domestic violence.
AB  - Medical students, as physicians of the future, are well aware of the impact of
      violence and abuse on the health of patients and the well-being of society and
      are eager to learn all they can about family and intimate violence while in
      medical school. Yet, most academic and practicing physicians-the "experts" who
      teach students the art and science of medical practice-have received little or no
      education themselves in this area. In order for medical students to enter
      practice feeling more comfortable with their important roles in the prevention of
      and intervention in family and intimate violence, they need to receive
      comprehensive, integrated education during all four years of medical school. This
      article outlines the rationale for such education from the student's perspective,
      describes the impact of such efforts on medical students, and suggest specific
      strategies for implementing curricular reforms designed to fully train medical
      students in the knowledge, skills, and attitudes necessary to practice
      effectively in this area.

PMID- 9008583
TI  - Bridging prevention and practice: public health and family violence.
AB  - Public health approaches the primary prevention of family violence by focusing on
      surveillance, the identification of risk factors, and the development,
      evaluation, and dissemination of interventions. Physicians and other health care
      providers are crucial in this process because they are in a unique position to
      identify at-risk individuals and populations and to implement both broad-based
      and targeted preventive and intervention initiatives. Incorporating public health
      principles into medical education and medical practice not only can reduce the
      severity of this epidemic by strengthening efforts in early detection and expert
      intervention but also can create effective primary prevention, an important
      necessary step towards eradicating every disease or condition. This article
      discusses the role of public health professionals in preventing family and
      intimate violence. It notes specific findings from public health research,
      including the cycle of violence and the need to incorporate issues of abuse
      across the life span, and other factors, into medical education. Addressing
      family and intimate violence in a caring and sensitive manner is difficult, and
      incorporating public health principles into medical education and medical
      practice can forge an effective partnership between medical practitioners and
      public health professionals. This new partnership represents both an important
      challenge and a unique opportunity to understand family and intimate violence and
      thus to develop and evaluate effective short- and long-term solutions.

PMID- 9008584
TI  - Barriers to physician identification and treatment of family violence: lessons
      from five communities.
AB  - Since the Surgeon General's Workshop on Violence and Public Health (Leesburg,
      Virginia, October 27-29, 1985), a substantial literature has developed about the
      limitations of the health care response to family violence. Many contributions
      have reflected experiences in limited numbers of practice settings (e.g., a
      single emergency department or hospital). Until 1990, however, there had been no
      community-based studies. The Robert Wood Johnson Foundation asked a
      multidisciplinary team from Education Development Center, Inc. and Children's
      Hospital (Boston) to investigate the health care responses to family violence in
      five diverse communities. This qualitative study, comprising more than 480
      interviews, provided a vivid picture of the barriers facing physicians and other
      health care providers in identifying, treating, and referring victims of family
      violence. It also illuminated the relations of the health care systems in these
      communities with other key sectors, including agencies and the judiciary. The key
      findings from the five-city study remain relevant because (1) it is the only
      large-scale, multi-community-based assessment of the barriers facing physicians;
      (2) it identified, or in some cases confirmed, both institutional and educational
      barriers limiting the effectiveness of even the most committed physicians; (3) it
      identified, or in some cases confirmed, specific areas of knowledge, attitudes,
      and skills development that should be incorporated in medical education; and (4)
      its conclusions continue to be reflected in subsequent contributions to the
      literature. In each of these ways, therefore, it informs the other articles in
      this supplement.

PMID- 9008585
TI  - Intimate partner abuse: developing a framework for change in medical education.
AB  - Addressing domestic violence presents unique challenges for individual physicians
      and for the institutions that shape medical education and practice. In addition
      to the need to acquire new knowledge and skills, clinicians must confront the
      feelings and social beliefs that shape their responses to patients, develop new
      frameworks for understanding complex social issues, and generate collaborative
      models for working in partnership with community groups. Educators, in turn, must
      provide training experiences that foster the development of those understandings
      and skills, institutional structures that support their integration into routine
      practice, and faculty who model nonabusive behaviors in all aspects of training
      and medical care. Expanding traditional medical paradigms to address the multiple
      dimensions of abuse can lay the groundwork for such a process. In addition,
      students need to be encouraged to develop awareness of the larger social forces
      that affect all of our lives and health, and to recognize their potential roles
      as community members in ending domestic violence. This article offers suggestions
      for changes in the structure of medical education as part of generating a health
      care system contribution to ending abuse in this society. Creating a model for
      fostering nonabusive relationships at individual and institutional levels within
      the health care system can provide a paradigm for transforming the conditions
      under which abuse is tolerated.

PMID- 9008586
TI  - Interpersonal violence and the education of physicians.
AB  - Physicians in every field of practice can expect to be called upon to care for
      patients whose lives have been affected by interpersonal violence. Although the
      medical profession has begun to acknowledge the appropriate role of physicians in
      screening, diagnosis, and treatment of interpersonal violence, these areas have
      not been fully addressed in the curricula of most medical schools. Competencies
      in the understanding of violence and its treatment are proposed for medical
      students, residents, and practicing physicians. By the time of graduation, all
      medical students should be able to demonstrate appropriate attitudes, core
      knowledge, and basic skills in assessment and intervention of patients at risk
      from or experiencing violence. During postgraduate training, residents should
      amass specialized knowledge and skill concerning the spectrum of injuries and
      illnesses they may encounter in clinical practice. Faculty development efforts
      should address the advancement of faculty who are well trained in a scholarly
      approach to teaching and research in this field. This paper describes methods by
      which educational efforts in interpersonal violence can be introduced into
      medical education. Proposed goals and objectives for curriculum development in
      schools of medicine, along with an implementation plan, are offered.

PMID- 9008587
TI  - Curricular principles for health professions education about family violence.
AB  - The curricular principles presented here arose from a national conference of
      experts in dealing with family violence from medicine, nursing, and dentistry.
      The conference, held in March 1994 in Oklahoma City, Oklahoma, was supported by
      The Robert Wood Johnson Foundation. The conference's work was based upon the
      premise that an integrated approach to health-professional education in family
      violence would be more effective than single approaches. The group developed a
      set of principles for identification of specific goals in knowledge, skills and
      practices. With those in mind, three levels of education were identified:
      knowledge, skills, and practices that should be taught to all health
      professionals (called "Family Violence 101"); advanced levels for primary care
      practitioners for comprehensive, longitudinal care; and knowledge, skills, and
      attitudes for specialty practitioners for specific, directed, intensive
      interventions appropriate to the specialties (called "Family Violence 201"); and
      additional education and training for those practitioners who wish to be
      consultants, investigators, and teachers of intervention in cases of family
      violence (called "Family Violence 301"). These recommendations are presented in
      the hope that health-professional schools and societies will implement them,
      thereby improving the health professions responses to this epidemic.

PMID- 9008588
TI  - Responding to domestic violence: a coordinated response by a consortium of
      teaching hospitals. Domestic Violence Task Force, Conference of Boston Teaching
      Hospitals.
AB  - Increasingly, health care providers are recognizing their role in the struggle
      against domestic violence. Although individual institutions around the country
      have developed protocols and programs in conjunction with community providers,
      there has been no unified health care effort. In May 1995, the Conference of
      Boston Teaching Hospitals (COBTH)--a collaborative body of the 14 academic
      hospitals and medical centers in the Boston area--formed the COBTH Domestic
      Violence Task Force. This task force, chaired by the president of Children's
      Hospital, represents the first time that hospital administrators and clinical
      staff have joined forces to deal with this issue. Critical to this effort were
      (1) the recognition that the hospitals have a responsibility to respond to
      patients as well as employees who are battered, (2) that in order for this work
      to move forward and become integrated into hospital systems, the involvement of
      senior medical staff and management is necessary, (3) that training and education
      must be ongoing and penetrate all levels of staff, and (4) that this work must be
      collaborative, with hospital staff working across disciplines and with community
      service providers. This paper outlines the year-long work of this Committee,
      including specific objectives and recommendations.

PMID- 9008589
TI  - The diverse faces of violence: minority women and domestic abuse.
AB  - In research and clinical practice, the failure to detect and/or elicit
      information about domestic abuse is exacerbated by social, economic, and cultural
      factors. Because domestic violence cannot be separated from the cultural and
      social context in which it occurs, such factors must be integrated into research
      studies and the development of interventions. The National Institutes of Health's
      expanded guidelines on the inclusion in its clinical trials of women from all
      ethnic and racial backgrounds, along with an increased recognition of the
      importance of socioeconomic and psychosocial factors in health and disease, has
      strengthened efforts to improve understanding of domestic violence in diverse
      communities. The involvement of researchers from minority communities is crucial
      to the success of such efforts. Study of the relationships among race, ethnicity,
      culture, and domestic violence must be fully incorporated into medical school
      curricula to sensitize students and enable them to develop the skills needed to
      detect more effectively deal with, and ultimately prevent, family and intimate
      violence.

PMID- 9008591
TI  - Resources for faculty development in family violence.
AB  - Medical school curriculum committees struggle not only with which topics to teach
      but also with how to teach them effectively. Even when curriculum committees or
      medical school deans decide to offer instruction in a new topic area, or an issue
      about which their students have a strong interest, they can find it difficult to
      find support for development of curriculum and faculty who are qualified to teach
      in the area. When the topic or course addresses family violence, there are
      additional challenges for the institution and for individual faculty members.
      This article describes the unique challenges facing faculty development in the
      field of family violence, reviews standard approaches to faculty development, and
      offers specific suggestions for accessing existing resources and faculty
      development opportunities.

PMID- 9008590
TI  - Evaluation of the module on domestic violence at the UCLA School of Medicine.
AB  - Physicians and other hospital staff have a unique opportunity to assist victims
      of abuse. It is imperative that they develop the skills necessary to identify and
      diagnose cases and provide the support and referral services needed to help
      victims end the cycle of violence. This paper describes a comprehensive
      evaluation of the instructional design, implementation, and learning outcomes of
      the Domestic Violence Module at the University of California, Los Angeles (UCLA)
      School of Medicine to determine the effectiveness of this curriculum in helping
      medical students develop such skills. Expert reviewers found it to be an
      innovative, well-planned curriculum, and students and faculty tutors expressed a
      great deal of interest in and satisfaction with the course as a whole. However,
      the different evaluation components identified the same areas for improvement:
      (1) students need more opportunity to practice skills and receive feedback during
      the module, (2) there is inconsistency across classes in what is learned, and (3)
      tutors need better preparation sessions. The student outcomes reflected these
      needs and therefore suggest that the study may be useful in determining the
      components of an effective curriculum. After the training, the students reported
      significant increases in their feelings of self-efficacy and in their intentions,
      especially in comparison with a group of control students. Therefore, the module
      seems to be successful in inspiring medical students to work with victims of
      abuse.

PMID- 9008592
TI  - Practical recommendations for supporting medical students and faculty in learning
      about family violence.
AB  - Family violence as a discipline of medical study and practice is now an integral
      component of medical education. Education about family violence should be spread
      among many courses and delivered by a variety of faculty throughout the four
      years of medical school. Medical faculty are just beginning to appreciate the
      complexities of teaching about family violence, in particular the issues involved
      in dealing with their own and their students' attitudes, feelings, and reactions
      to patients who have suffered from abuse. This article discusses the complex
      issues that need to be considered in preparing medical students and a broad range
      of medical faculty to teach and practice effectively in this area, and offers
      practical recommendations for approaching this complex issue. It notes the need
      for support services for both faculty and students, ranging from treatment for
      ongoing individual issues to an institutional plan or protocol for dealing with
      potential crises.

PMID- 9008593
TI  - HRSA's strategies to combat family violence.
AB  - This paper discusses the efforts of the Health Resources and Services
      Administration (HRSA) to work with a broad constituency to combat and ultimately
      prevent family violence. In partnership with states and communities, HRSA
      implements programs to strengthen health care infrastructure, support direct
      community-based service delivery, and educate health care providers. Soliciting
      and incorporating community input are critical steps in designing innovative
      training approaches to deal with pressing health concerns, such as the efforts of
      family violence in a community. This type of collaboration is evident in HRSA's
      programs such as the Area Health Education Centers, the Geriatric Education
      Centers, and the AIDS Education and Training Centers. Health care delivery
      systems and special health interventions must respond to the far-reaching effects
      of family violence. HRSA is devising a comprehensive strategy to guide program
      development in violence intervention. This strategy would build on successful
      models of education, prevention, and service delivery, as well as identification
      of critical areas for collaboration between community activists, researchers,
      epidemiologists, health care providers, policymakers, academicians, survivors,
      philanthropists, representatives from state and local government, and the faith
      community.

PMID- 9008594
TI  - Accentuate the positive: we are better than guidelines.

PMID- 9008595
TI  - Mononuclear phagocytes and rheumatoid synovitis. Mastermind or workhorse in
      arthritis?

PMID- 9008596
TI  - Disease patterns and tissue cytokine profiles in giant cell arteritis.
AB  - OBJECTIVE: To determine whether clinical heterogeneity in patients with giant
      cell arteritis (GCA) is correlated with different patterns in the tissue-specific
      inflammatory response. METHODS: Twenty-three patients with typical
      histomorphologic findings of GCA were grouped according to the presence or
      absence of jaw claudication and/or visual abnormalities, fever, concomitant
      polymyalgia rheumatica (PMR), and histologic evidence of giant cell formation.
      The inflammatory response in temporal artery biopsy specimens was characterized
      by semiquantification of cytokine messenger RNA (mRNA) transcripts using reverse
      transcriptase-polymerase chain reaction, followed by oligonucleotide
      hybridization with cytokine-specific probes. Clinical patterns were then
      correlated with profiles of tissue cytokines. RESULTS: Inflammatory cytokines
      were expressed in all temporal artery tissues. In situ synthesis of interleukin-2
      (IL-2), interferon-gamma (IFN gamma), and IL-1 beta mRNA, but not of IL-10 and IL
      12 mRNA, distinguished different patterns of inflammation, and these patterns
      correlated with clinical manifestations of the disease. Patients with evidence of
      ischemic symptoms, indicated by jaw claudication and/or visual symptoms,
      typically expressed higher concentrations of IFN gamma mRNA (P = 0.008) and IL-1
      beta mRNA (P = 0.02). Presence of fever was correlated with lower copy numbers of
      IFN gamma (P = 0.02). Formation of giant cells in the granulomatous infiltrates
      was associated with the local synthesis of IFN gamma mRNA (P = 0.003). Tissue
      from GCA patients with concomitant PMR contained higher levels of IL-2 mRNA
      transcripts (P = 0.001). CONCLUSION: Variations in the clinical presentation of
      GCA were correlated with cytokine mRNA expression in the affected temporal
      arteries. Differences in the effector functions of tissue-infiltrating T cells
      distinguished disease patterns in which either local ischemic symptoms or
      systemic involvement was dominant, or in which there was co-occurrence of PMR.
      Definition of different patterns of inflammation in GCA might, therefore,
      facilitate the design of differentiated therapeutic approaches.

PMID- 9008597
TI  - Long-term treatment of systemic lupus erythematosus with cyclosporin A.
AB  - OBJECTIVE: To evaluate the efficacy of long-term treatment with cyclosporin A
      (CSA) in systemic lupus erythematosus (SLE). METHODS: Thirty patients with SLE
      whose condition was either poorly responsive or unresponsive to treatment with
      steroids and/or cytotoxic drugs were enrolled in a prospective, nonrandomized
      study of CSA. Patients with hypertension or hypercreatinemia were excluded.
      Disease activity was evaluated according to the systemic lupus activity measure.
      Assessments were made prior to study entry and after 6, 12, 18, and 24 months.
      RESULTS: Twenty-seven patients completed at least 24 months of treatment with
      CSA. The mean disease activity score significantly decreased after 6 months of
      therapy (P < 0.01); this result was maintained throughout the study. A
      conspicuous steroid-sparing effect was observed following administration of CSA
      (P < 0.01). Side effects included hypertrichosis (63% of patients), paresthesias
      (23%), gastrointestinal symptoms (20%), gingival hyperplasia (17%), hypertension
      (10%), tremors (7%), and nephrotoxicity (13%). No significant changes in serum
      creatinine levels were observed. CONCLUSION: CSA represents a helpful second
      choice treatment for patients with active SLE. Administration of CSA necessitates
      expert and careful followup of patients.

PMID- 9008598
TI  - Magnetic resonance imaging of the brain and cerebral proton spectroscopy in
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the prevalence and extent of cerebral changes in
      patients with systemic lupus erythematosus (SLE) by magnetic resonance imaging
      (MRI) and magnetic resonance spectroscopy (MRS). METHODS: SLE patients (47 women)
      and controls (25 women) underwent 1.5T MRI. A semiautomated segmentation
      technique calculated cerebrospinal fluid (CSF) and brain volumes. Proton MRS of
      the frontal and parieto-occipital white matter yielded metabolite ratios of N
      acetyl groups (NA), choline, and creatine. RESULTS: Compared with the control
      group, the SLE patients more often had cerebral atrophy on MRI (32% versus 0%),
      confirmed by an increase in the CSF to intracranial volume ratio. The patients
      also had old infarcts and hemorrhages (8.5% versus 0%) and more small white
      matter lesions (23% versus 8% had > 5 such lesions). MRS showed relative
      reduction of NA peaks. Although no patient was studied when acutely ill, prior
      neurologic involvement was related to abnormal findings. CONCLUSION: MRI and MRS
      are helpful in the investigation of cerebral complications of SLE. There are
      chronic changes which may be ischemic in nature. Their precise cause,
      consequences, and prevention are current challenges.

PMID- 9008599
TI  - The relationship of socioeconomic status, race, and modifiable risk factors to
      outcomes in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To study the relationship of race, socioeconomic status (SES),
      clinical factors, and psychosocial factors to outcomes in patients with systemic
      lupus erythematosus (SLE). METHODS: A retrospective cohort was assembled,
      comprising 200 patients with SLE from 5 centers. This cohort was balanced in
      terms of race and SES. Patients provided information on socioeconomic factors,
      access to health care, nutrition, self-efficacy for disease management, health
      locus of control, social support, compliance, knowledge about SLE, and
      satisfaction with medical care. Outcome measures included disease activity
      (measured by the Systemic Lupus Activity Measure), damage (measured by the
      SLICC/ACR damage index), and health status (measured by the SF-36). RESULTS: In
      multivariate models that were controlled for race, SES, center, psychosocial
      factors, and clinical factors, lower self-efficacy for disease management (P < or
      = 0.0001), less social support (P < 0.005), and younger age at diagnosis (P <
      0.007) were associated with greater disease activity. Older age at diagnosis (P <
      or = 0.0001), longer duration of SLE (P < or = 0.0001), poor nutrition (P <
      0.002), and higher disease activity at diagnosis (P < 0.007) were associated with
      more damage. Lower self-efficacy for disease management was associated with worse
      physical function (P < or = 0.0001) and worse mental health status (P < or =
      0.0001). CONCLUSION: Disease activity and health status were most strongly
      associated with potentially modifiable psychosocial factors such as self-efficacy
      for disease management. Cumulative organ damage was most highly associated with
      clinical factors such as age and duration of disease. None of the outcomes
      measured were associated with race. These results suggest that education and
      counseling, coordinated with medical care, might improve outcomes in patients
      with SLE.

PMID- 9008600
TI  - Assessment of systemic lupus erythematosus disease activity by medical record
      review compared with direct standardized evaluation.
AB  - OBJECTIVE: Clinical studies of systemic lupus erythematosus (SLE) often
      necessitate assessment of previous disease activity, which is sometimes only
      possible by retrospective evaluation of information from the medical record.
      Using the Systemic Lupus Activity Measure (SLAM), the present study compared an
      assessment of disease activity obtained by chart abstraction with a direct
      clinical assessment. METHODS: A chart SLAM was obtained using information
      abstracted from the clinic notes of 46 patients with SLE who were being followed
      up at a referral center. Chart SLAM scores were compared with SLAM scores derived
      from an independent assessor's direct clinical evaluation. RESULTS: Direct SLAM
      and chart SLAM scores were correlated (r = 0.67 by Spearman's rank correlation, P
      = 0.0001). Chart review scores for disease activity tended to be lower, but to an
      inconsistent degree, reflecting both under- and overestimation of disease
      activity. The overall misclassification rate on a 3-category scale (mild,
      moderate, or severe activity) was 59%. CONCLUSION: Although chart SLAM scores
      were highly correlated with direct SLAM scores, misclassification of disease
      activity by chart review cannot be rectified. Thus, in research, medical record
      review should not be used as a proxy for the direct SLAM, nor should it be
      considered comparable with clinical assessments in the analysis of disease
      activity.

PMID- 9008601
TI  - A randomized, double-blind study comparing twenty-four-week treatment with
      recombinant interferon-gamma versus placebo in the treatment of rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate the safety and efficacy of recombinant interferon-gamma
      (rIFN gamma) in patients with active rheumatoid arthritis (RA), using an
      induction and maintenance regimen. METHODS: A multicenter, randomized, double
      blind trial of 197 patients with RA was conducted to compare the effects in a
      group receiving 50 micrograms of rIFN gamma, given subcutaneously in a decreasing
      regimen over 24 weeks, with those in a placebo group receiving injections of
      placebo at the same time frequency. Standard clinical assessments were performed.
      RESULTS: Both rIFN gamma and placebo produced a significant improvement from
      baseline to end point visit for most measurements (except erythrocyte
      sedimentation rate, duration of morning stiffness, and grip strength), but no
      significant intergroup differences were seen. Regarding adverse effects, mild
      local skin reactions at the site of injection were observed, and among the
      cardiovascular events, mild edema and vasodilatation were reported. CONCLUSION:
      IFN gamma proved no more effective than placebo in this group of patients with
      RA. IFN gamma was well tolerated in this group of patients, without increased
      toxicity compared with placebo.

PMID- 9008602
TI  - T cell cytokine pattern in the joints of patients with Lyme arthritis and its
      regulation by cytokines and anticytokines.
AB  - OBJECTIVE: To investigate whether type 1 helper (Th1) or Th2 cytokines are found
      in the joints of patients with Lyme arthritis, and whether the cytokine pattern
      can be modulated by cytokines or anticytokines. METHODS: The cytokine pattern in
      the joints of 10 patients with Lyme arthritis was investigated. Expression of
      interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha),
      interleukin-4 (IL-4), and IL-10 was measured by enzyme-linked immunosorbent assay
      (ELISA), after stimulation of synovial fluid mononuclear cells (SFMC) with
      Borrelia burgdorferi (Bb) in the supernatant. Expression of cytokine messenger
      RNA and protein in synovial membrane (SM) and nonstimulated SFMC was studied
      using semiquantitative reverse transcriptase-polymerase chain reaction and
      immunohistologic techniques. The effects of recombinant cytokines or neutralizing
      anticytokine antibodies on cytokine production in Bb-stimulated SFMC were
      investigated by ELISA. RESULTS: SFMC produced high amounts of IFN gamma and TNF
      alpha, but little or no IL-4, upon stimulation with Bb antigen, indicating a Th1
      type cytokine pattern. In SM, IFN gamma was detectable in all patients, while the
      other cytokines were less frequently found. Serial sections of SM revealed that
      all cytokines were located in the same area. The Th1 response, especially the
      production of TNF alpha, could be down-regulated in vitro by both endogenous and
      exogenous IL-10, but not by IL-4 or anti-IL-12. CONCLUSION: A Th1-type cytokine
      pattern was found in the joints of patients with Lyme arthritis. This Th1
      response could be down-regulated by IL-10, suggesting insufficient IL-10
      production in vivo.

PMID- 9008603
TI  - Accumulation of soluble Fas in inflamed joints of patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To examine the concentration of the soluble form of the Fas molecule
      (sFas) in the serum and synovial fluid of patients with rheumatoid arthritis (RA)
      and osteoarthritis (OA). METHODS: The concentration of sFas in the serum of 15
      normal subjects and in the synovial fluid and serum of 45 RA patients and 13 OA
      patients was determined. The erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP) level, and the level of several cytokines in serum and synovial
      fluid were also determined. RESULTS: The synovial fluid concentration of sFas was
      higher in RA than in OA patients (P < 0.005). The synovial fluid level of sFas
      correlated weakly with serum levels of CRP (r = 0.541), the ESR (r = 0.499), and
      with synovial fluid levels of interleukin-2 (IL-2) receptor (r = 0.544), IL-6 (r
      = -0.529), and intercellular adhesion molecule 1 (r = 0.514). Reverse
      transcription-polymerase chain reaction analysis revealed that synovial cells and
      infiltrating mononuclear cells expressed sFas messenger RNA in RA patients.
      CONCLUSION: Our data suggest that accumulation of sFas in the joint cavity of RA
      patients may inhibit apoptosis and exacerbate the inflammatory process.

PMID- 9008604
TI  - Fas and Fas ligand expression in the salivary glands of patients with primary
      Sjogren's syndrome.
AB  - OBJECTIVE: To assess the role of Fas-mediated apoptosis in the salivary glands of
      patients with primary Sjogren's syndrome (SS). METHODS: Expression of Fas, Fas
      ligand (FasL), and bcl-2 in salivary gland biopsy material was detected in situ
      by immunohistochemical staining and reverse transcriptase-polymerase chain
      reaction. DNA fragmentation in apoptotic cells was assessed by the enzymatic
      incorporation of labeled nucleotides (digoxigenin-dUTP). RESULTS: The acinar
      epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis.
      The majority of infiltrating lymphocytes in SS were Fas+ and bcl-2+, while few
      lymphocytes expressed FasL. In situ detection of apoptosis showed minimal cell
      death of lymphocytes, particularly in dense periductal foci. Lymphocytic cell
      death was significantly lower (P < 0.0001) in these foci compared with that in
      the interstitium. CONCLUSION: Infiltrating lymphocytes in the focal lesions of
      the salivary glands of patients with SS are blocked in their ability to commit to
      apoptosis, even though they may express Fas. The presence of bcl-2 in these cells
      may explain their inability to undergo apoptosis. The acinar epithelial cells, in
      contrast, may undergo Fas-mediated apoptosis. These results suggest that the Fas
      death pathway may be an important mechanism leading to the glandular destruction
      found in SS.

PMID- 9008605
TI  - Evidence of qualitatively altered nociception in patients with fibromyalgia.
AB  - OBJECTIVE: To investigate the perception of pain in tender muscles of patients
      with fibromyalgia. METHODS: Twenty-five women with fibromyalgia and 25 healthy
      women were examined. Seven different pressure intensities were used to palpate a
      highly tender muscle and a largely normal muscle. Subjects then recorded their
      response to induced pain on a visual analog scale. The examiner was blinded to
      each subject's response. RESULTS: The stimulus-response function for pressure
      versus pain recorded for normal muscle was well described by a power function.
      For highly tender muscle, the stimulus-response function was displaced toward
      lower pressures and, more importantly, it was linear, i.e., qualitatively
      different from that of normal muscle. CONCLUSION: This study demonstrates that
      nociception is qualitatively altered in patients with fibromyalgia, which is
      consistent with recent findings in other patients with tender muscles. The data
      strongly indicate that fibromyalgic pain, at least in part, is due to aberrant
      central pain mechanisms.

PMID- 9008606
TI  - Similarities of specificity and cofactor dependence in serum antiphospholipid
      antibodies from patients with human parvovirus B19 infection and from those with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To assess the phospholipid specificity and immunoglobulin isotype of
      antiphospholipid (aPL) antibodies in patients with acute parvovirus B19
      infection. METHODS: Specificity of aPL and isotype distribution in the negatively
      charged phospholipids, cardiolipin and phosphatidyl serine, and in the neutral
      phospholipid, phosphatidyl ethanolamine, were measured in the sera of patients
      with acute parvovirus B19 infections (n = 12), in those with other acute viral
      infections (n = 10), and in those with syphilis (n = 15) by enzyme-linked
      immunosorbent assays. The dependence of anticardiolipin (aCL) binding on the
      presence of beta 2-glycoprotein I (beta 2-GPI) as a binding cofactor was assessed
      in these same groups, and was compared with sera from systemic lupus
      erythematosus (SLE) patients (n = 11) with raised aCL antibody reactivity.
      RESULTS: Antibodies against any of the 3 phospholipids were found in all 3 groups
      of patients with infections (B19 in 11 of 12 patients, other viral infections in
      8 of 10 patients, and syphilis in 14 of 15 patients). B19 patients' sera
      contained predominantly IgG antibodies against the negatively charged
      phospholipids, cardiolipin and phosphatidyl serine, and differed in their
      specificity and isotype distribution from those found in the other 2 patient
      groups. B19-associated aCL increased their binding to antigen in the presence of
      beta 2-GPI as a binding cofactor, similar to aCL found in SLE patients, but
      unlike antibodies from patients with other viral infections or from those with
      syphilis. CONCLUSION: The results show the remarkable similarity in specificity
      of aPL antibodies between B19-infected patients and SLE patients, and raise the
      question of whether parvovirus infection may be a trigger for the development of
      aPL antibodies in autoimmune diseases.

PMID- 9008607
TI  - Cross-reactivity of human IgG anti-F(ab')2 antibody with DNA and other nuclear
      antigens.
AB  - OBJECTIVE: To characterize immunologic specificity and possible antiidiotype
      activity of IgG anti-F(ab')2 in normal subjects as well as in patients with
      active and inactive systemic lupus erythematosus (SLE). METHODS: IgG anti-F(ab')2
      and anti-double-stranded DNA (anti-dsDNA) were affinity isolated from
      immunoadsorption columns of F(ab')2 and dsDNA linked to Sepharose 4B. Affinity
      purified IgG anti-F(ab')2 (APAF) and affinity-isolated IgG anti-dsDNA (APAD) were
      tested by enzyme-linked immunosorbent assay (ELISA) for other cross-reacting
      specificities including anti-Sm, anti-Sm/RNP, and anti- Crithidia binding. Anti
      DNA specificity of APAF and APAD was assayed by S1 nuclease treatment of heat
      denatured DNA. Rabbit antiidiotypic antisera were prepared by immunization with
      APAF and APAD from normal subjects and SLE patients and absorption with
      insolubilized human Cohn fraction II (Fr II). VL and VH regions of 5 monoclonal
      IgM antibodies with anti-F(ab')2/anti-DNA specificity generated by Epstein-Barr
      virus B cell stimulation were sequenced by polymerase chain reaction and
      characterized for VH and VL subgroup. APAF and APAD were also examined by high
      resolution electron microscopy for possible ring forms indicative of
      antiidiotypic V-region interactions. RESULTS: APAF from normal subjects,
      representing 0.08-0.18% of serum IgG, showed striking relative concentrations of
      both anti-F(ab')2 and anti-DNA, as well as anti-Sm and anti-Sm/RNP ELISA
      reactivity. Both APAF and APAD reacting with F(ab')2 or dsDNA on the ELISA plate
      could be cross-inhibited by F(ab')2 or DNA in solution. Anti-DNA reactivity in
      normal APAF and APAD was much more sensitive to S1 nuclease treatment than
      similar fractions from SLE patients. Neither APAF nor APAD from controls produced
      positive antinuclear immunofluorescence or positive Crithidia staining, whereas
      these were strongly positive using SLE APAF and APAD. Absorbed rabbit antisera
      against normal or SLE APAF and APAD showed strong ELISA reactivity against both
      APAF and APAD, but no residual reactivity with normal Fr II. VL and VH sequencing
      of monoclonal human IgM antibodies showing both anti-F(ab')2 and anti-DNA
      reactivity showed relative VH3, V kappa 1 or VH1, V kappa 3 restriction. No
      evidence of ring forms or V-region "kissing" dimers was obtained when normal or
      SLE APAD or APAF was examined by high-resolution electron microscopy. CONCLUSION:
      IgG anti-F(ab')2 in both normal subjects and SLE patients represents a
      polyreactive Ig subfraction with concomitant anti-DNA, anti-Sm, and anti-Sm/RNP
      specificities. Anti-DNA reactivity in SLE is qualitatively different from that in
      normal APAD and APAF since normal APAD and APAF anti-DNA is much more sensitive
      to S1 nuclease digestion of denatured dsDNA. APAF and APAD share distinct V
      region antigens which may be related to prominent VH3 or VH1 antigenic
      components. No evidence for in vivo complexing of anti-DNA and anti-F(ab')2 as
      ring forms or antiidiotype-IgG complexes was observed during ultrastructural
      studies. In both normal individuals and SLE patients, APAF may represent a small
      polyreactive IgG subfraction which also contains antinuclear and anti-DNA
      specificities.

PMID- 9008608
TI  - Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis
      and other glomerulonephritides.
AB  - OBJECTIVE: To investigate potential mechanisms by which CD40L-mediated signals
      may be involved in the pathogenesis of lupus glomerulonephritis (GN). METHODS:
      Renal in situ CD40L and CD40 expression was examined in patient biopsy specimens.
      Immunohistochemical studies were performed on frozen sections utilizing anti
      CD40L monoclonal antibody (MAb), anti-CD40 MAb, or control MAb. As controls, we
      analyzed normal kidney specimens and specimens obtained from patients with IgA
      nephropathy, focal segmental glomerulosclerosis, minimal change disease,
      idiopathic membranous GN, and antineutrophil cytoplasmic antibody-positive pauci
      immune GN. Staining distribution was noted and staining intensity scored on a
      semiquantitative scale of 0 (no staining) to 3+ (intense staining). RESULTS: In
      normal kidney, CD40 was expressed on parietal epithelial cells, mesangial cells,
      endothelial cells, and distal tubules but not proximal tubules. Glomerular and
      tubular CD40 expression was markedly up-regulated in class III and class IV lupus
      GN, where there was intense staining of crescents, proximal and distal tubules,
      and interstitial mononuclear cells. In contrast, CD40 expression in class V lupus
      GN was similar to that in normal kidney. Interstitial mononuclear cells
      expressing CD40L were present in class IV lupus GN. However, these findings were
      not unique to lupus GN: up-regulation of CD40 and CD40L expression was similarly
      observed in other inflammatory renal diseases. CONCLUSION: This study shows that
      CD40 is expressed on a variety of renal parenchymal and non-parenchymal cells in
      normal kidney. Renal CD40 expression is up-regulated in class III and class IV
      lupus nephritis, as well as in other inflammatory renal diseases, and is
      associated with the presence of CD40L+ mononuclear cells.

PMID- 9008609
TI  - Incidence and disease associations of a proteinase 3-antineutrophil cytoplasmic
      antibody idiotype (5/7 Id) whose antiidiotype inhibits proteinase 3
      antineutrophil cytoplasmic antibody antigen binding activity.
AB  - OBJECTIVE: To evaluate the potential of a monoclonal proteinase 3-antineutrophil
      cytoplasmic antibody (PR3-ANCA) antiidiotype autoantibody (5/7 anti-Id) as a
      candidate for specific immunotherapy in Wegener's granulomatosis (WG), and to
      estimate the immunodiagnostic value of the corresponding idiotype (5/7 Id).
      METHODS: We analyzed the incidence of 5/7 Id in patients with ANCA-associated
      vasculitides (WG, microscopic polyangiitis, Churg-Strauss syndrome), in disease
      controls (systemic lupus erythematosus patients), and in healthy donors. We then
      investigated the presence of 5/7 Id in relation to disease stage, clinical
      activity, and organ manifestations in 86 patients with WG. Finally, we
      investigated the ability of the 5/7 anti-Id reagent to inhibit the binding of PR3
      ANCA to corresponding antigen in 19 WG patients. RESULTS: The incidence of 5/7 Id
      was significantly more frequent in WG patients (43 of 86; 50%). We did not find a
      significant correlation between the prevalence of idiotype expression and disease
      activity or organ manifestations. Further, we demonstrated in vitro suppression
      of PR3-ANCA antigen binding activity by 5/7 anti-Id in 11 of 19 WG patients who
      were positive for 5/7 Id. CONCLUSION: This study shows that 5/7 Id is a common
      idiotype with a significantly increased incidence in WG and that 5/7 anti-Id
      inhibits PR3-ANCA antigen binding activity. Based on these observations, we
      conclude that 5/7 anti-Id is a promising tool for the development of a specific
      immunotherapy for WG.

PMID- 9008610
TI  - Prevention of cytokine-induced changes in leukocyte adhesion receptors by
      nonsteroidal antiinflammatory drugs from the oxicam family.
AB  - OBJECTIVE: To explore the effect of the nonsteroidal antiinflammatory drugs
      (NSAIDs) piroxicam and meloxicam on quantitative and qualitative changes in
      leukocyte adhesion receptors induced by cytokines and other activation stimuli.
      METHODS: The expression of CD11b and L-selectin during neutrophil activation with
      tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony
      stimulating factor (GM-CSF), FMLP, phorbol myristate acetate (PMA), and calcium
      ionophore A23187 was assessed by flow cytometry. Enzyme-linked immunosorbent
      assays were used to quantitate soluble L-selectin shed after neutrophil
      stimulation. Enzyme release was measured to determine neutrophil degranulation by
      proinflammatory stimuli. Changes in affinity state of beta 1 and beta 2 integrins
      after neutrophil and T lymphocyte stimulation were assessed, by flow cytometry,
      using the monoclonal antibodies (MAb) HUTS-21 (anti-beta 1) and CBRM1/5 (anti
      CD11b), which recognize activation-dependent epitopes on these two integrins.
      RESULTS: Pretreatment of neutrophils with either NSAID prevented the changes in L
      selectin and CD11b expression induced by TNF alpha, GM-CSF, and FMLP, but not
      those induced by PMA or A23187. Furthermore, piroxicam significantly decreased
      the amount of L-selectin shed by cytokine-treated neutrophils, whereas it did not
      exert this effect on PMA- or A23187-treated neutrophils. Piroxicam also decreased
      the release of gelatinase and lysozyme induced by TNF alpha, but not by PMA.
      Interestingly, piroxicam prevented the conformational changes that beta 2
      integrins underwent upon activation of neutrophils: the appearance of the
      activation epitope of CD11b, detected by the CBRM1/5 MAb, was blocked by
      piroxicam in TNF alpha-treated neutrophils. Moreover, in chemokine-treated T
      lymphocytes, the expression of activation epitopes on beta 1 integrins was also
      diminished by piroxicam. In contrast, this NSAID did not affect the beta 1
      integrin conformational changes induced by PMA or Mn++. CONCLUSION: Our results
      indicate that members of the oxicam family are able to interfere with events of
      neutrophil function, such as their degranulation and cytokine-mediated activation
      changes in adhesion molecules, both in neutrophils and in lymphocytes. Such
      effects may significantly contribute to the antiinflammatory activity of these
      drugs.

PMID- 9008611
TI  - Suppression of type II collagen-induced arthritis by the endogenous estrogen
      metabolite 2-methoxyestradiol.
AB  - OBJECTIVE: To evaluate the antiarthritic properties of 2-methoxyestradiol, an
      endogenous metabolite of estradiol, on type II collagen-induced arthritis (CIA)
      in DBA/1 mice. METHODS: The effects of treatment with 2-methoxyestradiol on the
      development of CIA were evaluated clinically and histologically. The in vitro
      effects of 2-methoxyestradiol on lymphocyte and endothelial cell proliferation
      and differentiation were analyzed by standard methods. RESULTS: The development
      of CIA was significantly suppressed by 2-methoxyestradiol. Incubation with 2
      methoxyestradiol suppressed the in vitro proliferation of endothelial cells,
      indicating that this compound down-regulates angiogenesis. Endothelial cell
      production of nitric oxide (NO) was also down-regulated by 2-methoxyestradiol. In
      contrast to estradiol, 2-methoxyestradiol exerted neither detectable feminizing
      effects on the sex organs nor inhibition of leukocyte development in
      hematopoietic organs. CONCLUSION: The development of CIA is suppressed by 2
      methoxyestradiol, possibly via inhibition of angiogenesis. Diminished NO
      production could be of importance in vivo because it is a potent proinflammatory
      mediator. Since 2-methoxyestradiol exerts only mild side effects compared with
      estradiol, it is an interesting candidate for therapeutic use in inflammatory
      diseases.

PMID- 9008612
TI  - Degradation of type II collagen, but not proteoglycan, correlates with matrix
      metalloproteinase activity in cartilage explant cultures.
AB  - OBJECTIVE: To determine the contribution of certain matrix metalloproteinases
      (MMPs) to the degradation of proteoglycan and type II collagen in cartilage.
      METHODS: Bovine nasal and articular cartilage explants were cultured with
      recombinant human interleukin-1 alpha (IL-1 alpha) for up to 4 weeks. Release of
      proteoglycan and type II collagen into the medium was determined by colorimetric
      assay and immunoassay, respectively. The activity of MMPs in the medium was
      assayed using a quenched fluorescent substrate, as well as with a collagen fibril
      assay, by zymography, and in Western immunoblots. In some experiments, the
      effects of specific MMP inhibitors on type II collagen degradation were studied.
      RESULTS: In cultures of nasal cartilage with IL-1 alpha, almost all the
      proteoglycan was released within the first week, whereas there was no detectable
      release of type II collagen for the first 2 weeks of culture. A rapid period of
      almost complete dissolution of the collagen occurred in the third or fourth week.
      MMP activity measured using a quenched fluorescent substrate was negligible
      during the first 2 weeks of culture but was substantially increased in the third
      week of culture, at the time of collagen degradation. Similarly, there was a
      large increase in collagenolytic activity (by collagen fibril assay) and
      gelatinolytic activity (by zymography) during the third week of culture.
      Articular cartilage cultured with IL-1 alpha lost proteoglycan progressively
      during the 4-week period; however, there was no loss of type II collagen from the
      matrix in that time and no significant increase in MMP activity. The loss of type
      II collagen from nasal cartilage stimulated with IL-1 alpha was inhibited by
      BB87, an inhibitor of both collagenases and gelatinases, and by BB3003, a
      selective inhibitor of gelatinase A. In Western immunoblots, procollagenase and
      active interstitial collagenase could be readily detected in nasal cartilage
      cultures. Some procollagenase 3 and active collagenase 3 was also shown to be
      present. CONCLUSION: MMP activity correlates with degradation of type II
      collagen, but not proteoglycan, in cartilage cultures. Interstitial collagenase,
      collagenase 3, and gelatinases are all likely to contribute to cleavage and
      removal of collagen from the cartilage matrix. The proteinase(s) responsible for
      aggrecan breakdown remains unclear.

PMID- 9008613
TI  - Methotrexate-associated appearance and rapid progression of rheumatoid nodules in
      systemic-onset juvenile rheumatoid arthritis.
AB  - Rheumatoid nodules are a rare extraarticular manifestation of juvenile rheumatoid
      arthritis (JRA), usually detected in patients with polyarticular-onset disease
      and positive rheumatoid factor (RF). To date, there has not been a published
      report of rheumatoid nodules in systemic-onset JRA. Low-dose methotrexate (MTX)
      is generally considered to be the most useful second-line drug in the treatment
      of polyarticular JRA. In adult RA, MTX has been shown to be associated with
      appearance and progression of rheumatoid nodules. This report describes a 3-year
      old girl with RF-negative, antinuclear antibody-negative systemic JRA who
      developed multiple rheumatoid nodules on the scalp and trunk during MTX therapy.
      The first nodule developed on the scalp 6 months after MTX treatment was
      initiated. Previous treatment with azathioprine was not associated with
      nodulosis. This represents an atypical case of MTX-associated accelerated
      nodulosis in systemic JRA, and raises the problem of treatment plan modification
      in the presence of this side effect.

PMID- 9008614
TI  - Systemic vasculitis and myelodysplastic syndromes. A report of two cases.
AB  - Two cases of systemic vasculitis associated with myelodysplastic syndromes are
      reported. Vasculitis may develop either before or after the diagnosis of a
      hematologic disorder, and it responds to treatment with high-dose
      corticosteroids.

PMID- 9008615
TI  - The arthropathy of fibroblastic rheumatism.
AB  - Fibroblastic rheumatism (FR) is a relatively rare syndrome characterized by the
      association of multiple cutaneous nodules with polyarthritis. The unique
      histologic finding in the skin and synovium of patients with FR is a
      proliferation of myofibroblast-like cells within a background matrix of collagen.
      The occurrence of erosive arthritis has not been emphasized in previous
      descriptions of FR. We describe a patient with FR who presented with symmetric
      polyarthritis, skin thickening, and dermal nodules. Despite treatment with
      prednisone and D-penicillamine, he developed a progressive, destructive
      polyarthropathy that mimicked multicentric reticulohistiocytosis.

PMID- 9008616
TI  - Tuberculosis cutis colliquativa during long-term immunosuppressive therapy for
      rheumatoid arthritis.

PMID- 9008617
TI  - Defining polymyalgia rheumatica: comment on the article by Helfgott and Kieval.

PMID- 9008618
TI  - Frequency of a normal erythrocyte sedimentation rate in patients with active,
      untreated arteritis temporalis and polymyalgia rheumatica: comment on the article
      by Helfgott and Kieval.

PMID- 9008619
TI  - Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis: comment
      on the article by Gutierrez-Urena et al.

PMID- 9008620
TI  - Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis: comment
      on the article by Gutierrez-Urena et al.

PMID- 9008621
TI  - Incidence of pancytopenia with methotrexate treatment of rheumatoid arthritis in
      Germany: comment on the article by Gutierrez-Urena et al.

PMID- 9008622
TI  - T cell help and antiphospholipid antibody immunogenesis.

PMID- 9008623
TI  - Recall of brand-name gold sodium thiomalate: are generics reliable?

PMID- 9008624
TI  - Complement and complement regulatory proteins in human tears.
AB  - PURPOSE: The complement system is part of the innate defense system of the body,
      and it contributes to inflammatory conditions. The current study examined tears
      for the presence of complement components, the activity of the components, and
      the presence of regulatory components. METHODS: The significance of a functional
      complement system in tears was examined in four ways. First, the presence and
      concentration of complement components in tear samples (open-eye, closed-eye, and
      reflex tears) was examined by sandwich enzyme-linked immunosorbent assay. Second,
      the presence of an active pathway in each tear type was established by
      supplementation of complement-deficient sera. Third, Western blotting of tear
      samples was used to determine whether complement components were activated in
      tears. Fourth, the presence of regulatory components was examined by enzyme
      linked immunosorbent assay and by the inhibition of the ability of tears to
      supplement deficient sera. RESULTS: Components C1q, C3, factor B, C4, C5, and C9
      were detected in closed-eye tears. Only C3, factor B, and C4 were detected in
      open-eye and reflex tears. Tears were able to supplement complement-deficient
      sera, indicating that the components were in an active state. Complement
      components C3, factor B, C4, and C9 were activated in closed-eye tears. The
      regulatory protein decay-accelerating factor was found only in closed-eye tears.
      Lactoferrin, another regulatory protein present in all tear types, was shown to
      inhibit complement-mediated red blood cell lysis, although the inhibition by
      closed-eye tear lactoferrin was reduced compared to that isolated from other tear
      types. CONCLUSIONS: This study has demonstrated that the complement system in
      tears was functionally active and that the concentration of all components was
      increased greatly in closed-eye tears. In spite of the presence of regulatory
      proteins, proteins of the complement cascade in tears were shown to be activated.

PMID- 9008625
TI  - Localization of tumor necrosis factor receptor messenger RNA in normal and herpes
      simplex virus-infected mouse eyes.
AB  - PURPOSE: To investigate the distribution of p75 and p55 tumor necrosis factor
      receptor (TNFR) mRNA in normal mouse eyes and in mouse eyes acutely infected with
      McKrae strain herpes simplex virus (HSV). METHODS: In situ hybridization with
      antisense 35S-labeled riboprobes for p55 and p75 TNFR subtypes was used in
      uninfected and HSV-infected mouse eyes. Controls included the use of sense
      riboprobes and corneas inoculated with vehicle alone. RESULTS: In uninfected and
      infected mouse eyes, in situ hybridization produced an autoradiographic signal
      for mRNA, encoding both p75 and p55 over the corneal endothelium, iris, ciliary
      body, choroid, and arachnoid layers of the optic nerve sheath. In addition, the
      signal was observed over scattered cells at the vitreoretinal interface. Signal
      for p75, but not p55, was observed over cells in the retinal ganglion cell layer.
      Acute HSV infection was accompanied by an intense leukocytic infiltrate in the
      conjunctiva, the corneal subepithelium and stroma, the anterior and posterior
      chambers, the iris root and ciliary body, and the vitreous cavity. In this
      setting, increased p75 and p55 mRNA signal was correlated closely with the number
      and location of receptor-bearing white blood cells. Signal over control sections
      hybridized with sense p75 and p55 TNFR cRNA probes was comparable to background.
      Signal over control eyes inoculated with sterile vehicle showed slight increased
      signal in the immediate vicinity of the traumatic keratitis, but otherwise it was
      comparable to that observed in uninfected animals. CONCLUSIONS: The observed
      distribution of p75 and p55 TNFR mRNA in normal and acutely infected mouse eyes,
      and particularly over the heavily vascularized uveal tract and over cells at the
      vitreoretinal interface, supports a role for TNF as a mediator of intraocular
      inflammation, perhaps as a key regulator of the blood-ocular barrier.

PMID- 9008626
TI  - Factors influencing the suitability of organ-cultured corneas for
      transplantation.
AB  - PURPOSE: To assess the influence of donor and storage factors on the suitability
      of organ-cultured corneas for penetrating keratoplasty (PKP) using multifactorial
      regression analysis. METHODS: Corneas (mean donor age, 57 years; standard
      deviation, 21 years) were stored by organ culture at 34 degrees C for up to 5
      weeks (mean, 22 days; standard deviation, 6 days). The endothelium was assessed
      by light microscopy, and corneas with < 2200 cells/mm2 were considered unsuitable
      for PKP. RESULTS: Of the 9250 corneas stored between 1992 and 1994, 59% were
      issued for PKP, 5% were discarded because of bacterial or fungal contamination,
      and 30% were unsuitable for PKP owing to endothelial deficiencies. Donor age had
      the strongest influence on suitability for PKP: > 80% of corneas from donors
      younger than 40 years of age were issued for PKP compared with only 45% of
      corneas from donors 80 years of age and older. There was an overall decline in
      the percentage of corneas suitable for PKP with increasing storage time, but the
      rate of this decline was inversely related to donor age. Cause of death and post
      mortem times to enucleation and to storage had only a small influence on
      suitability for PKP. CONCLUSIONS: Criteria based on endothelial assessment rather
      than on donor age allow corneas from donors of all ages, stored by organ culture
      for extended periods, to be used for PKP. Organ culture also allows corneas with
      bacterial or fungal contamination to be identified and discarded before they are
      grafted.

PMID- 9008627
TI  - Ultrastructural analysis of interleukin-1 beta-induced leukocyte recruitment to
      the rat retina.
AB  - PURPOSE: To examine, by ultrastructural analysis, the effect of the
      proinflammatory cytokine interleukin-1 beta (IL-1 beta) on the integrity of the
      rat retina and blood-retinal barrier (BRB) and to investigate the site of barrier
      leakage and the path of leukocyte infiltration into the retina. METHODS: After a
      single injection of IL-1 beta into the vitreous of the Lewis rat, leukocyte
      recruitment and retinal disease was assessed immediately and at frequent periods
      up to 14 days after injection by light and electron microscopy and by
      immunohistochemistry. The integrity of the BRB and the site of barrier disruption
      were evaluated using the large molecular weight tracer horseradish peroxidase.
      The phenotype of recruited leukocytes to the retina was assessed by
      ultrastructural morphology and immunohistochemistry. RESULTS: At 4 hours after
      the intravitreal administration of IL-1 beta, leukocytes were observed
      infiltrating the retina. Leukocyte infiltration increased gradually and peaked
      between 24 and 48 hours after injection. Associated with this infiltrate were
      edema and fibrin leakage, indicative of a breakdown in the BRB. This was
      confirmed by the demonstration of horseradish peroxidase extravasation across the
      retinal vascular bed, with leakage of the tracer through disrupted endothelial
      tight junctions. Using immunohistochemical and morphologic criteria, the majority
      of infiltrating cells were identified as monocytes-macrophages and neutrophils;
      occasionally, T cells were found. Ultrastructural analysis showed that the
      majority of cells entered the retina by migrating through retinal endothelial
      cells and that there was a smaller contribution from the ciliary body.
      CONCLUSIONS: The administration of IL-1 beta to the vitreous of the Lewis rat
      causes an acute, reversible retinal inflammatory response that is accompanied by
      breakdown of the vascular BRB. Interleukin-1 beta induces the recruitment of
      mononuclear and polymorphonuclear leukocytes that enter the retina predominantly
      through the retinal vasculature and that appear to migrate through retinal
      endothelial cells. These results suggest that IL-1 beta may be an important
      factor in the pathogenesis of human retinal inflammation.

PMID- 9008628
TI  - Vascular endothelial growth factor is present in glial cells of the retina and
      optic nerve of human subjects with nonproliferative diabetic retinopathy.
AB  - PURPOSE: To determine whether vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF), which have been implicated in the development of
      retinal and choroidal neovascularization, are present in the retinas and optic
      nerves of patients with diabetes before proliferative retinopathy appears.
      METHODS: Light microscopic immunocytochemistry using antibodies to VEGF, bFGF,
      vimentin, glial fibrillary acidic protein (GFAP), and factor VIII on frozen
      sections from eyes of patients with diabetes without proliferative retinopathy,
      eyes of patients without diabetes and without known ocular disease, and eyes with
      disciform age-related macular degeneration (ARMD). Retinal vascular digest
      preparations to evaluate microvascular abnormalities. RESULTS: Based on
      morphology and on GFAP and vimentin immunopositivity, retinas from all subjects
      with diabetes immunostained strongly to VEGF in elongated processes that appeared
      to be Muller cells. Glial cells within septa surrounding axons in the anterior
      optic nerve also immunostained for VEGF, as did endothelial cells of some
      posterior retinal blood vessels and some retinal pigment epithelial cells.
      Retinas from eyes with disciform ARMD immunostained for VEGF, though less
      extensively than did those of subjects with diabetes. Retinas and optic nerves
      from subjects without ocular disease were VEGF negative. Basic fibroblast growth
      factor was expressed minimally in the inner retinal layers of subjects with and
      without diabetes, but it was substantial in the photoreceptor layer of all eyes.
      Vascular endothelial growth factor immunopositivity was present in eyes with no,
      or little, retinal vascular anatomic abnormality in digest preparations.
      CONCLUSIONS: Vascular endothelial growth factor expression precedes retinal
      neovascularization in the retinas and the optic nerves of humans with diabetes.
      Its localization to glial cells of the inner retina and the anterior optic nerve
      suggests a relationship to neovascularization in these sites. That VEGF
      immunopositivity may occur when there is no anatomic evidence of retinal
      nonperfusion and little likelihood of retinal neovascularization suggests the
      possibility that ischemia may not be the sole stimulus for VEGF expression.

PMID- 9008629
TI  - Glucose metabolism in cat outer retina. Effects of light and hyperoxia.
AB  - PURPOSE: To determine the roles of oxidation and glycolysis with aerobic and
      anaerobic lactate formation in the glucose metabolism of the cat outer retina in
      light and darkness. METHODS: Blood was collected from a choroidal vein and from
      an artery, and veno-arterial differences in lactate concentration (Lac(v-a) were
      determined at increasing light intensities. Blood also was sampled under
      conditions of darkness, light, and hyperoxia and were analyzed for oxygen,
      glucose, and lactate concentrations with or without blood flow determinations.
      RESULTS: When the dark-adapted eye was subjected to increasing light intensities,
      there was a reduction in the Lac(v-a), indicating reduced glycolysis in the outer
      part of the retina as the rods saturated. In darkness, the mean lactate formation
      per retina was 0.409 mumol/minute, oxygen consumption was 0.198 mumol/minute, and
      glucose consumption 0.236 mumol/minute. In light, the corresponding figures were
      0.253, 0.166, and 0.123 mumol/minute. Hyperoxia reduced lactate formation and
      increased oxygen consumption in light and in darkness. CONCLUSIONS: Approximately
      80% of the glucose consumed by the outer retina is used primarily in aerobic
      lactate formation. Because it is more efficient, oxidation of glucose still
      accounts for most of the energy production in light and in darkness. Light
      reduces oxidation as well as aerobic and anaerobic lactate formation.

PMID- 9008631
TI  - Glucose dependence of glycolysis, hexose monophosphate shunt activity, energy
      status, and the polyol pathway in retinas isolated from normal (nondiabetic)
      rats.
AB  - PURPOSE: To measure glucose-dependent metabolic activities and selected
      parameters of the polyol pathway in retinas isolated from normal rats to test the
      hypothesis recently proposed by Van den Enden et al that incubation of whole
      retinas for 2 hours with elevated concentrations of glucose results in activation
      of the polyol pathway, which is the cause of a redox imbalance, as measured by an
      increase in the retinal cytosolic lactate-pyruvate ratio and a diabetic-like
      state. METHODS: Retinas obtained from nondiabetic rats and separated from other
      ocular tissues were incubated for several hours in incubation medium containing
      glucose at concentrations ranging from 5 to 30 mM. Measurements were made under
      aerobic and anaerobic conditions of lactic acid production, retinal adenosine
      triphosphate (ATP), lactic acid content, the hexose monophosphate shunt pathway,
      aldose reductase activity, and levels of sorbitol and galactitol. Morphology was
      examined by light microscopy at the end of the incubations. RESULTS: Incubation
      of isolated rat retinas with 20 mM glucose increased lactic acid production by
      approximately 25% in comparison to the rate observed in 5mM glucose under aerobic
      and anaerobic conditions. The content of ATP and lactate in the retinas after a 2
      hour incubation in the presence of oxygen and 20 mM glucose was equal to the
      amounts found in fresh tissues, whereas these metabolites declined, respectively,
      by 25% and 45% when 5 mM glucose was used. The activity of the hexose
      monophosphate shunt pathway in isolated rat retinas was not increased increased
      significantly when the concentration of glucose was raised from 5 to 30 mM.
      Aldose reductase activity and polyols were below our limits of detection, 0.5
      nmol/minute.mg protein and 3.5 nmol/retina, respectively, under all conditions
      tested. The morphologic appearance of the retina was similar in the presence of
      normal and high concentrations of glucose. CONCLUSIONS: These results show that
      incubation of isolated rat retinas, obtained from nondiabetic rats, with elevated
      concentrations of glucose for 2 hours leads to increases in glycolysis and a
      higher tissue content of lactic acid and ATP in comparison to values obtained
      with 5 mM glucose. However, the magnitude of the glucose-dependent increase in
      the retinal level of lactate in the current study and in that of Van den Enden et
      al is six to seven times greater than the calculated flux of glucose through the
      polyol pathway. These results, therefore, do not support the hypothesis of Van
      den Enden et al. Rather, it is suggested that supranormal concentrations of
      glucose yield more lactate and ATP in a whole retina because they optimize the
      supply of this essential nutrient to cells throughout the tissue by overcoming
      diffusional limitations that result when the retina is separated from its normal
      choroidal and intraretinal blood supplies.

PMID- 9008630
TI  - Mechanism of adrenomedullin-induced relaxation in isolated canine retinal
      arteries.
AB  - PURPOSE: To analyze the mechanism of action of adrenomedullin (AM), a peptide
      recently isolated from human pheochromocytoma, in isolated canine central retinal
      arteries and to compare the action of calcitonin gene-related peptide (CCRP).
      METHODS: Changes in isometric tension were recorded in helical strips of the
      arteries with and without the endothelium. RESULTS: Both AM and CGRP produced
      relaxation: EC50s were 2.62 and 0.71 x 10(-9) mol/l, respectively, and maximal
      relaxations were 85.1% and 84.3%, respectively. The AM-induced relaxation was
      endothelium-independent and unaffected by indomethacin, Ng-nitro-L-arginine,
      methylene blue, and glibencaalmide. Treatment with [8-37] CGRP markedly inhibited
      the relaxations caused by AM and CGRP. Treatment with a high concentration of
      sodium nitroprusside abolished the relaxation caused by nitroglycerin and atrial
      natriuretic peptide and reduced the relaxation caused by AM and CGRP. A high
      concentration of beraprost, a stable analog of prostaglandin I2, suppressed the
      response to AM and CGRP but not to nitroglycerin. CONCLUSIONS: Endothelium
      independent relaxations to AM of canine retinal arteries may be mediated
      primarily by intracellular cyclic adenosine monophosphate by stimulation of CGRP1
      receptors and partially by cyclic guanosine monophosphate; cyclic guanosine
      monophosphate is unlikely ot be produced by methylene blue-sensitive soluble
      guanylate cyclase. Prostanoids, nitric oxide, and adenosine triphosphate
      dependent K+ channel opening do not appear to be involved in the AM-induced
      relaxation.

PMID- 9008632
TI  - Function and visual impairment in a population-based study of older adults. The
      SEE project. Salisbury Eye Evaluation.
AB  - PURPOSE: The Salisbury Eye Evaluation (SEE) project investigates the impact of
      vision on functional status in a population-based sample of elderly persons. The
      prevalence of self-reports of functional status and the association with visual
      acuity loss are described. METHODS: A random sample of men and women 65 to 84
      years of age from Salisbury, Maryland were recruited for home interviews and
      clinic examinations. Of the eligible sample, 78% responded to the home
      questionnaire and 65% responded to the questionnaire and the clinic examination.
      Binocular visual acuity of each person was measured using ETDRS charts and
      protocols. Questions were asked concerning activities of daily living,
      instrumental activities of daily living, physical function, social interaction,
      and activities of daily vision. Analyses of the association of presenting visual
      acuity worse than 20/40 with the measures of function were carried out and
      adjusted for age, race, and sex. RESULTS: All measures of functional status
      showed a decline with age; women and blacks were more likely to report
      difficulties. The age-adjusted proportions of those with visual impairment were
      not significantly different between men and women (7.2% versus 6.7%; P = 0.60).
      Black persons had almost twice the rate (10.4%) of white persons (5.6%; P <
      0.001). Age, race, gender, and visual impairment were all significantly related
      to declines in functional status in multivariate models. CONCLUSIONS: Data on
      functional status in the project population were similar to national data and
      confirmed higher rates of disability in women and blacks. Binocular visual acuity
      worse than 20/40 appeared to have an impact on all the self-report measures of
      functional status. Further analyses on the interaction of vision with other
      comorbid conditions on function status clearly are indicated.

PMID- 9008634
TI  - Age-related changes in human blinks. Passive and active changes in eyelid
      kinematics.
AB  - PURPOSE: The authors analyzed eyelid kinematics in normal aging subjects to test
      the hypothesis that eyelid movements exhibit age-related changes and that blink
      disorders prevalent among the elderly, in turn, represent an outcome of normal
      aging processes. METHODS: The electromagnetic search coil technique was used to
      study blinks in normal human subjects for each decade from 40 to 89 years. Blink
      metrics (amplitude, peak velocity, and duration), main sequence relationships,
      and conjugacy were assessed. RESULTS: Mean amplitude and peak velocity of blinks
      decreased with age for spontaneous blinks and, to a lesser extent, for voluntary
      blinks. Some but not all, of this decline could be attributed to a peripheral
      phenomenon, narrowed palpebral fissure width. The spontaneous blink down phase
      main sequence slope also declined with age. By contrast, blink rate and the
      coordination of movements of the two eyelids--blink conjugacy--exhibited no
      change. CONCLUSIONS: These data demonstrate that disorders of blink systems
      typically seen in persons 50 years of age or older occur on a background of
      normal age-dependent changes in eyelid kinematics. Alterations in main sequence
      slope imply the operation of central adaptive systems during aging. Reduction in
      main sequence slope is interpreted as a reduction in aggregate orbicularis oculi
      motoneuron activity. Such a central neurologic adjustment in the motor output of
      blink systems may serve to compensate for an age-related increase in blink reflex
      excitability. Compensatory reduction in the main sequence relationship may offset
      a potentially hyperexcitable blink reflex, thereby reducing the likelihood of
      disorders such as blepharospasm. The authors conclude that although there are
      changes in the kinematics of blinking with age, such changes do not necessarily
      predispose an aging population to eyelid motility disorders.

PMID- 9008633
TI  - Models of open-angle glaucoma prevalence and incidence in the United States.
AB  - PURPOSE: To estimate the prevalence and incidence of open-angle glaucoma among
      black and white persons in the United States and to characterize quantitatively
      their life experience with glaucoma using a life table approach to estimate
      disease duration. METHODS: Review of published data on glaucoma combined with
      statistical models to estimate prevalence and incidence. RESULTS: The association
      of open-angle glaucoma with age was examined separately for white and black
      persons. By the year 2000, the number of persons in the United States with
      primary open-angle glaucoma is estimated to be 2.47 million (1.84 million white
      and 619,000 black Americans). A model using derived incidence rates for open
      angle glaucoma (OAG) and United States mortality data indicated that the average
      black American has OAG 27% longer than the average white American (16.3 years
      compared to 12.8 years). CONCLUSIONS: Meta-analysis to obtain pooled prevalence
      estimates for glaucoma provides useful information on length of disease and age
      distribution of those affected. It may assist in estimating treatment effects and
      associated costs to derive data that effect health care decisions.

PMID- 9008635
TI  - Long-term caloric restriction delays age-related decline in proliferation
      capacity of murine lens epithelial cells in vitro and in vivo.
AB  - PURPOSE: The goal of this study was to examine the effects of age and long-term
      caloric restriction on the proliferation capacity of murine lens epithelial (LE)
      cells in vitro and in vivo. METHODS: B6D2F1 (C57BL/6 X DBA/2) F1 mice 4 to 45
      months of age were obtained and fed either an ad libitum (AL) or a calorically
      restricted (CR) diet (60% of AL intake). Cellular proliferation capacity in vitro
      was measured using the colony size distribution assay for 10-day clonal growth of
      mouse LE cells. Proliferation rate in vivo was assayed using immunostaining for 5
      bromo-2'-deoxyuridine (BrdU) in mouse LE cells after 2-week osmotic pump delivery
      of BrdU. RESULTS: Proliferative capacity of cells from old AL mice decreased
      significantly in comparison to cells from young AL and old CR mice, as determined
      by the fractions of cells capable of forming small (no or one cell division) and
      large (four or more cell divisions) colonies in vitro. There was also a decline
      in cell replicative rate as measured by BrdU labeling index (LI) in vivo with
      increasing age in AL and CR mice. However, this decline was marked in AL mice
      between 10 and 30 months of age and minimal in CR mice. Significant differences
      in BudU LI between AL and CR mice occurred when animals were 30 months of age or
      older. This finding indicates that an age-related decline in cellular
      proliferation rate in vivo was delayed by CR. CONCLUSIONS: A significantly
      reduced proliferative capacity of LE cells is associated with increased age of
      mice and is delayed by long-term caloric restriction as measured in vitro and in
      vivo. How caloric restriction mediates its effects on LE cell proliferation
      remains to be investigated further.

PMID- 9008636
TI  - The Pax-6 homeobox gene is expressed throughout the corneal and conjunctival
      epithelia.
AB  - PURPOSE: Heterozygous defects in the highly conserved PAX6 homeobox gene are
      associated with aniridia, an inherited human disorder affecting several ocular
      structures, including the adult cornea. This work establishes the pattern of Pax
      6 gene expression in the surface epithelia of the late embryonic and adult eye.
      METHODS: Chick embryo sections and wholemounts, as well as adult mouse and monkey
      tissues, were analyzed by in situ hybridization and immunohistochemistry with
      probes specific to Pax-6. Western immunoblots were used to detect Pax-6 protein,
      and mRNA expression was analyzed by quantitative reverse transcription-polymerase
      chain reaction. RESULTS: In days 5 and 6 chick embryos, Pax-6 protein is found in
      the nuclei of all cells within the corneal epithelium and in the future
      conjunctiva. Although not detected in the cornea by in situ hybridization, Pax-6
      mRNA is, in fact, present at levels comparable to those observed in the retina.
      In the mature mouse, Pax-6 protein was expressed in all cells of the corneal
      epithelium, the limbus, and the entire conjunctiva. Similar results were obtained
      for the monkey cornea. CONCLUSIONS: These data indicate that in addition to its
      role in the embryo, Pax-6 is expressed strongly in surface epithelia of the adult
      cornea and conjunctiva. In cells of these tissues, the gene may function by
      regulating structural or secretory specializations. Pax-6 might play a direct
      role in the maintenance and proliferation of corneal stem cells, a vital process
      that appears to be defective in aniridia.

PMID- 9008637
TI  - Collagen fibril orientation in the human corneal stroma and its implication in
      keratoconus.
AB  - PURPOSE: The kind and the degree of preferred collagen fibril orientation in
      normal human corneal stroma were investigated as important qualities of the
      cornea with respect to its mechanical properties and, hence, to refractive
      surgery. To determine whether this information is relevant to corneal disease,
      the authors investigated collagen fibril orientation in several corneas with
      keratoconus. METHODS: By means of low-angle x-ray scattering, 17 normal human
      corneas and four corneas of eyes with keratoconus were investigated. RESULTS:
      Collagen fibrils in the normal human corneal stroma showed two preferred
      orientations orthogonal to each other. These were the horizontal and the vertical
      directions. The authors defined a degree of orientation gamma, determined to be
      gamma = 0.49 +/- 0.10 (mean +/- SD). This means that the excess of the
      preferentially oriented fibrils in relation to the total number of fibrils was
      approximately 49%. It follows from this value that approximately two thirds of
      the fibrils (66%) were within in a 45 degrees sector (+/-22.5 degrees) around the
      horizontal and vertical meridians, whereas approximately one third (34%) is
      oriented in the oblique sectors in between. No statistically significant
      variation of gamma within a central 7 mm zone could be detected in normal
      corneas. The orthogonal arrangement of the collagen fibrils was, however,
      profoundly altered in keratoconus, in which nonorthogonal orientations were found
      inside the apical scar. CONCLUSIONS: The normal human corneal stroma shows a
      considerable degree of structural anisotropy. It is characterized by two
      preferred collagen fibril orientations orthogonal to each other. Alteration of
      the regular orthogonal arrangement of the fibrils in keratoconus may be related
      to the biomechanical instability of the tissue.

PMID- 9008638
TI  - Endothelin receptor-mediated Ca2+ signaling and isoform expression in bovine
      corneal epithelial cells.
AB  - PURPOSE: Bovine corneal epithelial cells (BCEC) were cultured to determine
      whether endothelin (ET) receptor subtype stimulation affects ET isoform
      expression (ET-1, ET-2, and ET-3) through capacitative Ca2+ influx. To probe in
      the isolated bovine corneal epithelium (BCE) for ET isoform and ET (i.e., ETA and
      ETB) receptor gene expression. METHODS: [Ca2+]i transients were characterized
      with microfluorometry. Endothelin isoform and ET receptor gene expression were
      probed with RNase protection analysis. Enzyme-linked immunosorbent assay was used
      to measure levels of ET-1-like immunoreactivity (ET-1-LI) in conditioned medium.
      RESULTS: ET-1 (10(-6) M) increased [Ca2+]i more than twofold. After treatment
      with 10(-7) M alltrans retinoic acid (an inducer of differentiation), 10(-6) M
      sarafotoxin (S-6-c) (a selective ETB agonist), had a similar effect.
      Preincubation with either 5 microM U73122 (an inhibitor of IP8 formation) or 10
      microM cyclopiazonic acid, which depletes intracellular Ca2+ store content,
      eliminated ET agonist-mediated [Ca2+]i increases. With a nominally Ca(2+)-free
      solution containing 10 microM cyclopiazonic acid, simultaneous 10(-6) M ET-1 and
      extracellular Ca2+ additions transiently increased [Ca2+]i twofold, whereas 10(
      6) M S-6-c increased it by only 20%. This augmentation was eliminated by
      preexposure to either BQ123 (10 microM), selective ETA receptor antagonist,
      U73122 (5 microM), or SKF 96365 (3 x 10(-5) M), an inhibitor of stores-operated
      channels. ET-1, ET-2 isoforms, and ET receptor mRNAs were identified. S-6-c (10(
      6) M) increased the level of ET-1-LI after 12 hours by approximately ninefold.
      CONCLUSIONS: In BCEC, capacitative calcium influx is involved in mediating a
      positive feedback relationship between ETB receptor stimulation and ET protein
      expression. Identification of ET-1 and ET-2 gene expression in BCE strengthens
      the notion that this regulation could be autocrine mediated.

PMID- 9008639
TI  - Cytokeratin expression in normal human bulbar conjunctiva obtained by impression
      cytology.
AB  - PURPOSE: To document the cytokeratin expression patterns in the normal human
      conjunctival epithelium obtained directly from patients using impression
      cytology. METHODS: Impression cytology specimens were obtained from normal
      volunteers using pure nitrocellulose membranes rather than cellulose acetate. The
      31 volunteers of both sexes ranged in age from 18 to 79 years. Impression
      cytology specimens were analyzed for individual cytokeratins by either
      immunocytochemistry or electrophoresis with immunoblotting using a defined panel
      of monoclonal antibodies. RESULTS: Using the corroborative methods of
      immunocytochemistry and electrophoresis with immunoblotting, cytokeratins
      characteristic of nonkeratinized, stratified (K4 and K13), simple (K8 and K19),
      and glandular epithelia (K7) were present in the superficial layer (s) of normal
      human conjunctiva. Cytokeratins typical of keratinized epithelia (K1, K2, and
      K10) and the keratinization-related proteins filaggrin and involucrin were not
      expressed in normal conjunctival epithelium. CONCLUSIONS: The normal human
      conjunctiva demonstrates a unique cytokeratin expression pattern containing
      cytokeratins characteristic of nonkeratinized, stratified epithelia, as well as
      others more typical of a simple differentiation pattern, a glandular
      differentiation pattern, or both. These findings provide a foundation for
      examining changes in the cytokeratin expression pattern in diseased human
      conjunctival epithelium using impression cytology.

PMID- 9008640
TI  - Type XVII collagen (BP 180) in the developing avian cornea.
AB  - PURPOSE: Previous sequence analyses of hemidesmosomal BP 180/collagen XVII cDNA
      from human skin and of a similar chicken corneal cDNA showed some similarities,
      but major differences as well. The authors examined whether, in one species, the
      same mRNA is present in cornea and skin. They also studied the developmental
      expression of the molecule and compared it to the transmembrane hemidesmosome
      component, alpha 6 beta 4 integrin, and to the formation of hemidesmosomes
      themselves. METHODS: Cornea and skin BP 180/collagen XVII cDNAs were cloned by
      reverse transcription-polymerase chain reaction (RT-PCR) and sequenced.
      Developmental expression was evaluated by quantitative RT-PCR, immunoblotting,
      and immunofluorescence microscopy. alpha 6 beta 4 integrin was evaluated by
      immunofluorescence microscopy, and hemidesmosome formation was assessed by
      electron microscopy. RESULTS: The same alpha 1 (XVII) collagen/BP 180 mRNA is
      present in cornea and skin. The appearance of alpha 1 (XVII) collagen mRNA and
      protein shows similar temporal patterns of expression, with changes in the mRNA
      preceding those of the protein by approximately 2 days. The appearance of mature
      hemidesmosomes lags still further. Immunofluorescence histochemistry of alpha 1
      (XVII) collagen and alpha 6 beta 4 integrin shows that their developmental
      appearance is regulated closely. CONCLUSIONS: The differences between human BP
      180/collagen XVII and the chicken corneal molecule represent species divergence.
      The appearance of alpha 1 (XVII) collagen mRNA and protein is regulated closely,
      with the protein lagging. Mature hemidesmosomes, once present, have a low
      turnover rate. The developmental appearance of alpha 1 (XVII) collagen and alpha
      6 beta 4 integrin are regulated closely. However, the component responsible for
      initiating hemidesmosome formation remains unknown.

PMID- 9008641
TI  - Retinal tubulin binds macular carotenoids.
AB  - PURPOSE: To investigate the biochemical mechanisms responsible for the specific
      uptake, concentration, and stabilization of the carotenoids lutein and zeaxanthin
      in the macula. METHODS: Soluble extracts of bovine retina mixed with radioactive
      carotenoids were purified by hydrophobic interaction, ion exchange, and gel
      filtration chromatography. Carotenoid-associated proteins in these purified
      preparations were identified through photoaffinity labeling and protein
      microsequencing. Similar purifications on human macular tissue without the
      addition of exogenous carotenoids also were performed. RESULTS: Experiments on
      bovine retinal tissue demonstrated that tubulin is the major soluble carotenoid
      binding protein. When soluble extracts of human macular protein were examined,
      the endogenous carotenoids lutein and zeaxanthin were found to copurify with
      tubulin. CONCLUSIONS: Tubulin is found in abundance in the receptor axon layer of
      the fovea, where it can serve as a locus for the deposition of the high
      concentrations of macular carotenoids found there. The binding interaction of
      carotenoids and tubulin in the Henle's fiber layer could play an important role
      in the photoprotective effects of the macular carotenoids against the progression
      of age-related macular degeneration. The association of carotenoids with tubulin,
      a protein that can form highly ordered linear arrays, may provide an explanation
      for the dichroic phenomenon of Haidinger's brushes.

PMID- 9008642
TI  - Confocal imaging of Ca2+ signaling in cultured rat retinal pigment epithelial
      cells during mechanical and pharmacologic stimulation.
AB  - PURPOSE: The purpose of this study was to investigate the mechanism of Ca2+
      signaling in rat retinal pigment epithelial (RPE) cells during mechanical and
      pharmacologic stimulation and to analyze the pathway of intercellular
      communication during mechanical stimulation. METHODS: Subconfluent monolayers of
      RPE cells cultured for 3 to 7 days after isolation from 5- to 8-day-old Long
      Evans rats were analyzed using the fluorescent Ca2+ dye fluo-3 and confocal laser
      microscopy. Mechanical stimulation of a single cell was applied by a slight,
      brief touch with a glass capillary. RESULTS: Pharmacologic agents [Arg8]
      vasopressin, carbachol, adenosine triphosphate, substance P, fetal calf serum,
      and histamine all elicited, to some extent, a biphasic [Ca2+]i transient by
      releasing Ca2+ from InsP3-sensitive Ca2+ stores. Stretching cellular membranes by
      touching them with the glass capillary increased free intracellular calcium
      concentration ([Ca2+]i) in the mechanically stimulated cell. After a time delay
      of up to 1.5 seconds, it increased free intracellular calcium concentration as
      well in the two to three adjacent layers of neighboring cells, resulting in the
      centrifugal propagation of an intercellular Ca2+ wave. In the absence of external
      Ca2+, neither a [Ca2+]i rise in the mechanically stimulated cell nor a
      propagating Ca2+ wave in the neighboring cells was found. The Ca2+ influx was not
      inhibited by verapamil or by K+ depolarization, but the addition of Ni2+ reduced
      the influx, suggesting the involvement of cation channels sensitive to Ni2+. Ca2+
      entry during mechanical stimulation was followed by Ca2+ release from
      intracellular Ca2+ stores. This release did not occur after pretreatment of the
      cells with thapsigargin and was reduced by exposure to ryanodine. The propagation
      of the Ca2+ wave could be blocked by the gap-junction blocker halothane and
      partially by K(+)-rich solution. It can be assumed, therefore, that cultured RPE
      cells express functional gap junctions. CONCLUSIONS: Mechanical stimulation
      triggers a Ca2+ influx that is followed by intracellular Ca2+ release.
      Intercellular communication in RPE cells depends on the presence of functional
      gap junctions. Pharmacologic stimulation relies primarily on the release of Ca2+
      from intracellular Ca2+ stores.

PMID- 9008643
TI  - Retinal pigment epithelial cells from dystrophic rats form normal tight junctions
      in vitro.
AB  - PURPOSE: In the genetically defective Royal College of Surgeons (RCS) rat model
      for retinal degeneration, a breakdown occurs in the retinal pigment epithelial
      (RPE) cell tight junctions just as the photoreceptors begin to degenerate. These
      experiments sought to determine the impact of the RPE genetic defect on this
      alteration in the RPE cell tight junctions. METHODS: Retinal pigment epithelial
      cell cultures prepared from RCS and control rats were treated with hormonally
      defined medium (HDM), base medium conditioned by RCS or control retinas, or
      unconditioned base medium. The tight junctions formed by these cultures were
      assayed functionally by measuring transepithelial electrical resistance and
      permeability. Junction structure was evaluated by immunolocalization of the tight
      junction protein zonula occludens 1 and of the junction-associated actin
      microfilaments. RESULTS: Retinal pigment epithelial cultures from dystrophic rats
      formed structurally and functionally normal tight junctions when maintained in
      hormonally defined medium. The junctions remained stable when the medium bathing
      the apical surface was switched to base medium preconditioned by normal retinas.
      In contrast, cultures treated with medium preconditioned by degenerating
      dystrophic retinas or with unconditioned medium exhibited a breakdown in their
      tight junctions. CONCLUSIONS: Retinal pigment epithelial cells isolated from
      dystrophic RCS rats can form tight junctions normally in vitro. Normal, but not
      dystrophic, retinas release factors that support RPE tight junctions. Therefore,
      the junctional abnormality seen in dystrophic rat RPE cells in vivo is probably
      caused by the loss of trophic factors normally provided by the healthy neural
      retina rather than by a direct effect of the genetic defect on the tight
      junctions.

PMID- 9008644
TI  - Localization of upstream silencer elements involved in the expression of cone
      transducin alpha-subunit (GNAT2).
AB  - PURPOSE: To localize cis-acting elements involved in the expression of the cone
      specific G-protein, cone transducin alpha-subunit (GNAT2). METHODS: In this
      study, the authors used a genomic clone, HGLG3, to sequence 3139 base pairs of
      the upstream region of the GNAT2 gene and to localize cis-acting elements
      involved in the expression of GNAT2. Upstream elements were localized
      functionally by transfection of chloramphenicol acetyltransferase gene constructs
      containing nested deletions of this upstream region into WERI-Rb1 cells. Cell
      specificity of the localized elements was determined by transfection of the HeLa
      cells. Trans-acting factor-binding sites to functional cis-acting elements were
      determined by DNasel footprinting. Cell specificity of protein interaction with
      footprinted regions was tested by electrophoretic mobility shifts with nuclear
      extracts from WERI-Rb1 and HeLa cells. RESULTS: Transfection of WERI-Rb1 and HeLa
      cells revealed the presence of a strong, noncell-specific silencer region between
      -1130 and -23, a weak, cell-specific promoter between -151 and -10, and a
      stronger, noncell-specific element between +143 and +167. DNaseI footprinting
      showed three major footprints (S1, S2, and S3) between -807 and -176, indicating
      the binding sites for putative negative trans-acting factors. Individual
      footprinted sequences had similar electrophoretic mobility shifts when they were
      incubated with nuclear extracts from either WERI-Rb1 or HeLa cells, suggesting
      that these cells express the same negative factors. CONCLUSIONS: The expression
      of the GNAT2 gene is controlled by a strong silencer region, a weak upstream cell
      specific promoter, and a strong downstream element. The silencer region interacts
      with similar proteins from retina- and nonretina-derived cell lines.

PMID- 9008645
TI  - The SKILL Card. An acuity test of reduced luminance and contrast. Smith
      Kettlewell Institute Low Luminance.
AB  - PURPOSE: To design and evaluate a new vision test that combines low contrast and
      reduced illumination to stress the visual system and be sensitive to subtle
      alterations in function. METHODS: A simple new clinical test, the Smith
      Kettlewell Institute Low Luminance (SKILL) Card, is designed to measure spatial
      vision under conditions of reduced contrast and luminance using normal office
      lighting. The SKILL Card consists of two near acuity charts mounted back to back.
      One side has a chart with black letters on a dark gray background designed to
      simulate reduced contrast and luminance conditions. The other side has a high
      contrast, black-on-white letter chart. The SKILL score is the acuity loss (number
      of letters) between the light and dark sides. RESULTS: Age norms for a large
      normal population have been established and show that test scores increase with
      age, particularly after age 50. Repeatability is as good as that of standard
      Snellen acuity. The SKILL score is affected minimally by blur, but it is affected
      by large variations in light level. SKILL scores are sensitive to the presence of
      visual disease such as "recovered" optic neuritis. CONCLUSIONS: The SKILL card
      allows quick, reliable measurement of the effect of reduced luminance and
      contrast on acuity SKILL scores are not correlated with other vision measures in
      patients with optic neuritis, which shows that the SKILL card measures a
      different dimension of vision function than existing clinical tests.

PMID- 9008646
TI  - Motion detection deficits in infantile esotropia without nystagmus.
AB  - PURPOSE: To investigate whether adults with infantile strabismus but without
      latent nystagmus have abnormalities of horizontal motion detection. METHODS:
      Eleven adult subjects with infantile esotropia but without latent nystagmus and
      15 control subjects were required to detect the onset of motion and drift
      direction of a sinusoidal, spatial frequency grating that moved with linearly
      increasing velocity. The grating was presented monocularly in paracentral vision
      at an eccentricity of 16.5 degrees with a field size of 18 degrees. The contrast
      of the grating was just above contrast threshold for visibility. RESULTS: The
      mean velocity threshold for detection of motion was raised significantly in the
      patient group compared with the control group. Nine of the 11 subjects with
      infantile esotropia demonstrated directional asymmetry for the detection of
      motion. Thresholds were elevated more often when the grating was moving nasally
      in the squinting eye and temporally in the nonsquinting eye, and raised
      thresholds were more prevalent in the squinting eye. CONCLUSIONS: The findings
      indicate that in infantile esotropia, the presence of motion perception deficits
      are not always associated with the development of latent nystagmus. The
      predominance of nasally directed motion deficits in the squinting eye and
      temporally directed motion deficits in the nonsquinting eye was unexpected and
      may have been caused by abnormal development of cortical motion processing.

PMID- 9008647
TI  - Intraocular pressure in inbred mouse strains.
AB  - PURPOSE: To develop a protocol to measure the intraocular pressure (IOP) of
      living mice and to determine the IOP of genetically different mouse strains.
      METHODS: Eyes of anesthetized animals were cannulated with a very fine fluid
      filled glass microneedle. The microneedle was connected to a pressure transducer,
      and the pressure signal was analyzed with a computer system. Intraocular
      pressures of male C3H/He iota, C57BL/ 6 iota, A/iota, and BALB/c iota mice were
      determined. RESULTS: Differences in IOP were detected between genetically
      distinct mouse strains maintained in virtually identical environments. C3H/He
      iota was the strain with the highest average IOP (13.7 +/- 0.8 mm Hg). This
      strain average was 1.4 mm Hg higher than that for C57BL/6 iota (12.3 +/- 0.5 mm
      Hg; P = 0.14), 4.3 mm Hg higher than that for A/iota (9.4 +/- 0.5 mm Hg; P <
      0.001), and 6 mm Hg higher than that for BALB/c iota (7.7 +/- 0.5 mm Hg; P <
      0.001). CONCLUSIONS: The authors have developed an accurate and reliable
      procedure for measuring intraocular pressure in living mice. This procedure can
      detect IOP differences between groups of mice that differ by genotype.

PMID- 9008648
TI  - Identification of G-protein alpha-subunits during distinct stages of lens cell
      differentiation.
AB  - PURPOSE: The purpose of this study was to identify alpha-subunits of
      heterotrimeric guanosine triphosphate-binding proteins in lens cell populations
      at various stages of terminal differentiation. METHODS: Crude cell membranes were
      isolated from the annular pad, cortical fibers, and nuclear fibers of adult
      chickens and subjected to cholera and pertussis toxin-mediated ribosylation
      reactions. Specific labeling of toxin substrates was visualized after SDS-PAGE
      and radioautography. In complementary experiments, cell membranes were first
      separated by SDS-PAGE, transferred to a nitrocellulose support membrane, and
      probed with a panel of commercially available antibodies that recognize various
      classes of G-protein alpha-subunits. RESULTS: A cholera toxin substrate was
      identified in cortical fibers whose labeling was dependent on a soluble factor.
      No cholera toxin substrates were labeled in annular pad cells. Two pertussis
      toxin substrates were seen in the relatively undifferentiated annular pad and the
      more differentiated cortical fibers. Relative abundance of the pertussis toxin
      substrates differed between the two cell types. Antibody staining revealed the
      presence of alpha-subunits belonging to the Gs, G(o), and G(i), families
      throughout the lens. Molecular weight differences of G alpha 2 polypeptides were
      noted between annular pad and cortical fiber cells. CONCLUSIONS: These results
      suggest that G-protein-based signal transduction pathways continue to function in
      lens cells during various stages of terminal differentiation. Differences noted
      between annular pad and cortical fibers provide additional evidence that dynamic
      alterations in receptor-mediated processes may be responsible for the
      accumulation of differentiated characteristics during fiber formation. This also
      indicates that ocular pharmacologic intervention could affect various aspects of
      lens physiology throughout the process of fiber formation.

PMID- 9008649
TI  - Location and stability of rectus muscle pulleys. Muscle paths as a function of
      gaze.
AB  - PURPOSE: The paths of the rectus extraocular muscles (EOMs) are constrained by
      pulleys, connective tissue sleeves mechanically coupled to the orbital walls.
      This study sought to investigate, using high-resolution magnetic resonance
      imaging (MRI), the location and stability of EOM pulleys in normal subjects and
      those with strabismus. METHODS: Multiple contiguous coronal MRI scans spanning
      the anterior-to-posterior extent of the orbit during primary gaze, upgaze,
      downgaze, adduction, and abduction were analyzed digitally to determine the paths
      of the rectus EOMs. Pulley locations were inferred from EOM paths. RESULTS: Data
      for 10 orbits of six normal subjects established the normal paths of the rectus
      extraocular muscles in primary gaze. Muscle paths in primary position were highly
      uniform across normal subjects. In secondary gaze positions, rectus muscle paths
      at the level of the pulleys exhibited small but consistent shifts, relative to
      the orbit, opposite the direction of gaze, consistent with the expected
      mechanical effects of the intermuscular connective tissue suspensions of the
      pulleys. Twelve orbits of seven subjects with strabismus showed, as a group, no
      significant difference from normal in rectus muscle paths in primary gaze and no
      significant difference from normal in changes of muscle paths in secondary gaze.
      Two subjects with incomitant strabismus wer found to have grossly abnormal rectus
      muscle paths in primary gaze, suggesting heterotopic pulleys. Computer
      simulations of these heterotopic pulley locations accounted for the observed
      patterns of incomitant strabismus in both. CONCLUSIONS: High-resolution MRI can
      determine the location and sideslip of rectus EOM pulleys. Pulley position is
      highly uniform across normal subjects, consistent with the notion that musculo
      orbital tissue connections determine the pulling direction of the rectus EOMs. In
      normal subjects and subjects with strabismus, pulleys exhibit small shifts with
      eccentric gaze that are consistent with secondary intermuscular, but not musculo
      global, mechanical couplings. Heterotopic pulley position is a potential cause of
      incomitant strabismus.

PMID- 9008650
TI  - Effect of transforming growth factor beta-1 in endotoxin-induced uveitis.
AB  - PURPOSE: Transforming growth factor beta-1 (TGF beta-1) can modulate
      inflammation. Endotoxin-induced uveitis (EIU) is characterized by acute ocular
      inflammation related to the release of cytokines, including interleukin (IL)-6.
      The authors investigated the effect of TGF beta-1 on EIU in mice. METHODS: Three
      independent experiments were performed. Endotoxin-induced uveitis was induced in
      C3H/HeN mice by an injection of 200 micrograms of lipopolysaccharide (LPS). Two
      micrograms of TGF beta-1 in 0.1 ml phosphate-buffered saline (PBS) or 0.1 ml PBS
      alone was administered intraperitoneally at 8 hours after LPS injection. Twenty
      four hours after LPS injection, the aqueous humor of the right eyes was collected
      for leukocyte count, protein concentration, and IL-6 assay. Left eyes were
      processed for routine histology. RESULTS: TGF beta-1-treated mice showed less
      ocular inflammation histologically than to the animals that were given PBS. This
      was confirmed by decreases in leukocyte count, protein concentration, and IL-6
      level in the aqueous humor. CONCLUSIONS: TGF beta-1 inhibits the development of
      EIU. TGF beta-1 may be useful for the modulation of uveitis in humans.

PMID- 9008651
TI  - Modeling spatial integration and contrast invariance in visual pattern
      discrimination.
AB  - PURPOSE: Human pattern discrimination performance has been reported to be largely
      independent of stimulus contrast but to depend on stimulus area. The authors
      propose a model that combines the effects of spatial integration and contrast.
      The model is based on the computation of similarity between pattern templates in
      memory and signals to be discriminated using normalized correlation. There are
      also two sources of additive noise, one before and one after the computation of
      correlation. The model was compared with human observers in an orientation
      discrimination task. METHODS: Orientation discrimination thresholds of human
      observers were measured for sinusoidal gratings of various areas, contrasts, and
      spatial frequencies. A two-interval, forced-choice methods was used. The
      performance of the model was determined by using computer simulations. RESULTS:
      It was found that the effects of contrast and grating area were interrelated. The
      decrease of orientation thresholds as a function of grating area was considerably
      larger at low than at high contrast. On the other hand, orientation thresholds
      decreased clearly as a function of contrast at the smallest grating areas but
      hardly at all at the largest grating areas. The model accounted well for the
      experimental findings. CONCLUSIONS: Because the invariance of orientation
      discrimination with respect to stimulus contrast depended on area, the cause of
      the invariance appeared to occur after spatial integration. The model explains
      this so that, with increasing contrast or area, the normalized correlation
      gradually approached a constant value. The proportion of pretemplate noise became
      negligible compared to the constant posttemplate noise. Thus, total noise also
      approached a constant value. Hence, the signal-to-noise ratio and discrimination
      performance became constant.

PMID- 9008652
TI  - Fidelity assurance mechanisms of the brain with special reference to its
      immunogenic CNS compartment: their role in aging and aging-associated
      neurological disease.
AB  - The greater longevity of humans over other mammalian species is provided, in
      large part, by the complex neural circuitry of the brain. Assurance of the
      integrity of this circuitry is partly provided by its neural plasticity. The
      brain is also protected from adverse systemic phenomena by the blood-brain and
      blood-cerebrospinal fluid barriers. However, these barriers do not protect the
      brain from adverse phenomena that originate within the central nervous system.
      The brain and immune systems share many analogous characteristics; and an
      immunogenic compartment of the brain is described here that also has the capacity
      to assure the integrity of its neural circuits and its autonomy. Finally, the
      role of this compartment in aging and in aging-dependent diseases is discussed.

PMID- 9008653
TI  - A study of caloric restriction and cardiovascular aging in cynomolgus monkeys
      (Macaca fascicularis): a potential model for aging research.
AB  - Caloric restriction has been demonstrated to retard aging processes and extend
      maximal life span in rodents, and is currently being evaluated in several
      nonhuman primate trials. We initiated a study in 32 adult cynomolgus monkeys to
      evaluate the effect of caloric restriction on parameters contributing to
      atherosclerosis extent. Following pretrial determinations, at which time a
      baseline measure of ad libitum (ad lib) dietary intake was assessed, animals were
      randomized to an ad lib fed group (control) or a caloric restriction group (30%
      reduction from baseline intake). The animals are being evaluated for glycated
      proteins, insulin, glucose, insulin sensitivity measures, and specific measures
      of body fat composition by CT scans (e.g., intra-abdominal fat) over specified
      intervals. The results from the first year of observation demonstrate a
      significant diet effect on body weight, and specifically intra-abdominal fat.
      Further, insulin sensitivity has been significantly increased after 1 year of
      caloric restriction compared to the ad lib fed group. These studies indicate that
      caloric restriction has a marked effect on a pathologic fat depot, and this
      change is associated significantly with an improvement in peripheral tissue
      insulin sensitivity.

PMID- 9008654
TI  - Influence of fat intake and caloric restriction on bone in aging male rats.
AB  - Caloric and fat intake may have important skeletal consequences. To evaluate this
      possibility, skeletal effects of adult-onset caloric restriction (CR) at
      differing fat intakes were assessed in male Lobund-Wistar rats. At age 17 months,
      two groups of animals received an anti-obesity diet, restricted approximately 35%
      from individual ad libitum baseline calorie consumption, and two groups received
      a diet approximately 50% restricted. Dietary fat concentrations were 5, 15, 15,
      and 25% by weight, respectively. At ages 20, 24, 28, 30, and 32 months, ex vivo
      femoral bone densitometry and serum biochemical analyses were performed. Body
      weight (BW) decreased with time on CR in each group (p < .005), declining faster
      at the more severe restriction (p = .001). Femoral bone mineral contents (BMC)
      were also reduced. After adjusting for bone area and BW differences among groups,
      the only significant difference was a reduction in distal femur BMC in the 25%
      fat group subjected to more severe CR (p = .02). No differences were observed in
      serum parathyroid hormone, calcium, phosphorus, or creatinine. Femoral bone loss
      occurred with CR. This was entirely accounted for by reduction in BW. Higher
      dietary fat content did not affect BW in CR animals, but did result in lower
      distal femur BMC.

PMID- 9008655
TI  - Circulating antioxidants as determinants of the rate of biological aging in
      pigtailed macaques (Macaca nemestrina).
AB  - The effect of antioxidant activity on the rate of biological aging was studied in
      39 pigtailed macaques (Macaca nemestrina) 7-30 years of age. Scores of seven
      antioxidant compounds (vitamins C and E, carotenoids, urate, bilirubin,
      ceruloplasmin, and albumin) were combined to produce an antioxidant variable
      (AOx) that was tested for correlation with a second composite variable, rate of
      biological aging (RBA). RBA was formed from seven physiological variables that
      met a stringent set of criteria as biomarkers of aging. Potential effects of
      disease on RBA and AOx were excluded by experimental design and by statistical
      control using a composite index of disease (Dis) that was based on four measures
      of clinical history and pathology. The study produced three salient findings: (1)
      there was a significant inverse relation between AOx and RBA (i.e., animals that
      had high AOx scores had low RBA scores and vice versa); (2) the relation was
      independent of Dis effects, and (3) there was no significant relation between AOx
      and Dis independent of RBA (i.e., the correlation between AOx and Dis was
      dependent on the correlation of AOx with RBA). These results further validated
      the RBA variable as a measure of the rate of biological aging and supported the
      concept that antioxidant activity influences both the rate of biological aging
      and vulnerability to disease.

PMID- 9008656
TI  - Candidate biomarkers of aging: age-sensitive indices of immune and muscle
      function covary in genetically heterogeneous mice.
AB  - A longitudinal experiment was designed to test the hypothesis that individual
      mice differ in their aging rate and to validate candidate biomarkers proposed to
      measure the rate of aging. Mice were bred as the genetically heterogeneous
      progeny of a cross between CB6F1 mothers and C3D2F1 fathers. Half of the mice
      were fed ad libitum (AL group), and the other half were subjected to 60% calorie
      restriction (CR group). Each mouse was tested at about 9 months of age using age
      sensitive tests of immune status, and then again at about 12 months of age using
      age-sensitive tests of muscle function. The data were then analyzed using the
      method of partial least squares to determine the combinations of test weights
      that maximize the covariance of the weighted sum of immune measures with the
      weighted sum of muscle function measures. Both AL and CR mice exhibited a
      statistically significant relation between the immune status tests and the muscle
      function tests. Maximal covariance was obtained with a set of weighting
      coefficients consistent with our working hypothesis: mice with high levels of CD4
      memory T cells (which increase with age) also had relatively low levels of muscle
      strength and endurance. Low strength was associated with low CD8 cells in the AL
      mice, with high numbers of CD8 memory cells in the CR mice and with low CD3 cells
      in both diet groups. The partial least squares method generates composite indices
      of immune status and muscle function that can be evaluated as biomarkers of aging
      rate in these mice. Further work will be needed to assess whether these tests
      predict either longevity or the trajectory of change in other age-sensitive
      molecular and physiological traits.

PMID- 9008657
TI  - Heat-induced longevity extension in Drosophila. I. Heat treatment, mortality, and
      thermotolerance.
AB  - Survival data were collected on a total of 28,000 Drosophila melanogaster adults
      in order to investigate mortality patterns and induced physiological responses
      after a mild thermal stress. A brief, nonlethal heat treatment extends adult life
      span at normal temperatures by an average of 2 days (64), compared to nontreated
      controls of the same genotypes. Life expectancy is extended as a demographic
      consequence of reduced age-specific mortality over a period of up to several
      weeks after the heat treatment. Heat treatment also increases tolerance to
      subsequent, more severe thermal stress. Observations on single-sex populations
      suggest that heat-induced longevity extension is independent of the suppression
      of reproductive activity.

PMID- 9008658
TI  - Altered cellular heterogeneity as a possible mechanism for the maintenance of
      organ function in senescent animals.
AB  - We tested the hypothesis that an alteration in the functional heterogeneity of
      cell populations (i.e., changes occurring in sensitivity and responsiveness to
      external stimuli among individual cells) may be a mechanism by which some organs
      are able to resist age-related decrements in function. To this end, changes in
      cytoplasmic free calcium concentration ([Ca2+]i) following glucose stimulation of
      individual pancreatic beta cells isolated from male F344 rats of ages 6, 12, and
      26 mo were used as a model for evaluating responsiveness and sensitivity. Changes
      in [Ca2+]i of individual beta cells were monitored using fura-2
      microspectrofluorimetry. No differences were observed in [Ca2+]i or in insulin
      secretion per beta cell among the age groups at any of the glucose
      concentrations. However, the percentage of beta cells that were responsive to a
      stimulatory glucose concentration (> 5.5 mM) was significantly greater in islets
      from the 26-mo-old rats (76%) as compared to the 6- and 12-mo-old animals (63%
      and 65%, respectively). Of the responsive beta cells, a significantly greater
      percentage of those from the 26-mo-old rats (72%) responded at the lowest
      stimulatory glucose concentration (7.5 mM) as compared to the 6- and 12-mo-old
      animals (58% and 60%, respectively). These data suggest that the maintenance of
      organ function in older rats at a level comparable to that of younger animals may
      be accomplished, in part, by an increase in the percentage of cells that are
      responsive to stimuli and/or by an increase in the sensitivity of the responsive
      cells.

PMID- 9008659
TI  - Skeletal muscle fatigue and endurance in young and old men and women.
AB  - The effects of increasing age on skeletal muscle fatigue and endurance were
      assessed in 22 healthy young (14 men and 8 women; mean age, 28 +/- 6 years) and
      16 healthy old (8 men and 8 women; mean age, 73 +/- 3 years) individuals. All
      subjects performed 100 repeated maximum dynamic knee extensions at 90 degrees.s-1
      (1.57 rad.s-1) using an isokinetic dynamometer (Cybex II). Peak torque was
      recorded during every contraction, and for each individual the maximal voluntary
      contraction (MVC), the fatigue rate, the endurance level, and the relative
      reduction in muscle force were determined. MVC and endurance level were
      significantly lower in old men and women, but there was no discernible difference
      in relative muscle force reduction and fatigue rate between young and old
      individuals. We conclude that thigh muscles of older individuals are weaker than
      those of younger individuals, but relative to their strength, older individuals
      have similar properties as younger individuals with respect to muscle fatigue and
      endurance.

PMID- 9008660
TI  - Age patterns of the life table aging rate for major causes of death in Japan,
      1951-1990.
AB  - It has been widely supposed that human mortality from all causes increases with
      age nearly exponentially (at a constant rate) through adult ages except for very
      old ages, and that this exponential increase also holds fairly well for most
      major causes of death (CODs). However, the present analysis of death registration
      data for Japan, 1951-1990, reveals that the rate of age-related relative increase
      in mortality (the life table aging rate) changes with age significantly and
      systematically for many CODs. Above age 75, the mortality increase decelerates
      for most CODs; under age 75, it remains at a relatively stable pace for ischemic
      heart disease, decelerates for most major cancers, and accelerates for diseases
      related to a declining ability to maintain homeostasis (pneumonia, bronchitis,
      influenza, gastroenteritis, and heart failure). These results seem to suggest
      that significantly different types of senescent processes may underlie
      atherogenesis, oncogenesis, and immunosenescence.

PMID- 9008661
TI  - Postmenopausal acceleration of age-related mortality increase.
AB  - The force of natural selection to eliminate deleterious genes is attenuated with
      advancing age, allowing senescence to evolve. This suggests that a distinctly
      marked end of the reproduction period is likely to be followed by an acceleration
      of senescence. It is thus expected that menopause should trigger an acceleration
      of age-related mortality increase in human females. Such an abrupt initiation of
      mortality acceleration is not predicted for human males at the same ages, whose
      fecundity declines more gradually. Life table aging rate patterns for selected
      industrialized countries generally support this hypothesis. A cause-of-death
      decomposition analysis indicates that the sex differential in mortality
      acceleration is mainly due to cardiovascular diseases, which is consistent with
      the prevalent view that postmenopausal changes in the sex hormone status may
      affect lipoprotein metabolism, and in turn, raise the risk of arteriosclerosis.

PMID- 9008662
TI  - Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced
      men.
AB  - BACKGROUND: Substantial data from animal studies have demonstrated a stimulatory
      effect of dehydroepiandrosterone (DHEA) on immune function. However, little is
      known about the effects of DHEA on the human immune system. Since aging is
      associated with a decline in immune function and in DHEA production, we proposed
      that oral administration of DHEA to elderly men would result in activation of
      their immune system. METHODS: Nine healthy age-advanced men (mean age of 63
      years) with low DHEA-sulfate levels participated in this study. They were treated
      nightly with an oral placebo for 2 weeks followed by DHEA (50 mg) for 20 weeks.
      Fasting (0800h-0900h) blood samples were obtained at 4- to 8-week intervals for
      immune function studies and hormone determinations. Freshly isolated peripheral
      lymphocytes were used for flow cytometric identification of lymphocyte subsets,
      cells expressing the IL-2 receptor (IL-2R), mitogen stimulation studies, and for
      determining natural killer (NK) cell number and cytotoxicity. Levels of
      interleukin-2 (IL-2) and IL-6 secreted from cultured lymphocytes were determined
      under basal and mitogen stimulated conditions. Sera were analyzed for soluble IL
      2 Receptor (sIL-2R) levels, insulin-like growth factor-I (IGF-I) and IGF binding
      protein-I (IGFBP-I) concentrations. RESULTS: Baseline levels of serum DHEA
      sulfate (DHEAS), a stable marker of circulating DHEA levels, were 2 standard
      deviations below young adult values and increased 3-4 fold within 2 weeks. These
      levels were sustained throughout the duration of DHEA administration. When
      compared with placebo, DHEA administration resulted in a 20% increase (p < .01)
      in serum IGF-I, a decreasing trend in IGFBP-I, and a 32% increase in the ratio of
      IGF-I/IGFBP-I (p < .01). Activation of immune function occurred within 2-20 weeks
      of DHEA treatment. The number of monocytes increased significantly (p < .01)
      after 2 (45%) and 20 (35%) weeks of treatment. The population of B cells
      fluctuated with increases (p < .05) at 2 (35%) and 10 (29%) weeks of treatment. B
      cell mitogenic response increased 62% (p < .05) by 12 weeks unaccompanied by
      changes in serum IgG, IgA, and IgM levels. Total T cells and T cell subsets were
      unaltered. However, a 40% increase (p < .05) in T cell mitogenic response, 39%
      increase in cells expressing the IL-2R (CD25+) (p < .05), and 20% increase in
      serum sIL-2R levels (p < .01) were found at 12-20 weeks of DHEA treatment,
      suggesting a functional activation of T lymphocytes occurred. In vitro mitogen
      stimulated release of IL-2 and IL-6 was enhanced 50% (p < .05) and 30% (p < .01)
      respectively by 20 weeks of treatment without basal secretion being affected. NK
      cell number showed a 22-37% increase (p < .01) by 18-20 weeks of treatment with a
      concomitant 45% increase (p < .01) in cytotoxicity. There were no adverse effects
      noted with DHEA administration. CONCLUSION: Administration of oral DHEA at a
      daily dose of 50 mg to age-advanced men with low serum DHEAS levels significantly
      activated immune function. The mechanism(s) to account for the immunoenhancing
      properties of DHEA are unclear. Consideration is given to the potential role of
      an increase in bioavailable IGF-I, which by virtue of its mitogenic effects on
      immune cell function, may mediate the DHEA effects. While extended studies are
      required, our findings suggest potential therapeutic benefits of DHEA in
      immunodeficient states.

PMID- 9008663
TI  - Age differences in using a rapid step to regain balance during a forward fall.
AB  - BACKGROUND: Earlier studies showed that healthy old adults have substantially
      reduced abilities to develop joint torques rapidly. We hypothesized that this age
      decline would reduce abilities to regain balance once a forward fall is underway.
      The present study examined whether aging in fact reduces ability to regain
      balance by taking a single, rapid step upon release from a forward lean. METHODS:
      Ten young (mean age 24.3 yr) and ten old (72.8 yr) healthy males were released
      from a forward-leaning position and instructed to regain standing balance by
      taking a single step forward. Lean angle was successively increased until a
      subject failed to regain balance as instructed. Lower extremity motions and foot
      floor reactions were measured during the responses. Total response time was
      divided into reaction, weight transfer, and step times. RESULTS: At small lean
      angles, responses of old subjects were similar to those of the young. However,
      the mean maximum lean angle from which old could regain balance as instructed was
      significantly smaller than that for young (23.9 vs 32.5 deg, p < .0005). Within
      each age group, maximum lean angle correlated strongly with weight transfer time
      and step velocity. CONCLUSIONS: Substantial age-related declines in the ability
      to regain balance by taking a rapid step exist among healthy adults when the time
      available for recovery is short. The source of the decline seems largely to lie
      in the decrease with age of maximum response execution speed rather than in the
      sensory or motor programming processes involved in response initiation.

PMID- 9008664
TI  - Aging impairs release of central and peripheral cholecystokinin (CCK) in male but
      not in female rats.
AB  - BACKGROUND: Cholecystokinin (CCK) is an important bioactive peptide which
      stimulates pancreatic enzyme secretion and is also a neuromodulator in the
      central nervous system. We examined whether CCK release from the central and
      peripheral tissues was decreased in old animals, and whether there were sex
      related differences. METHODS: Young (5-10-month-old) and old (25-29-month-old)
      male and female Wistar rats were used. Synaptosomes were prepared from the
      cerebral cortex, and the vascularly perfused duodenojejunum was isolated to
      examine central and peripheral CCK release, respectively. In some young female
      rats, 21 days after bilateral ovariectomy, the peripheral CCK release and the
      changes in CCK mRNA levels were examined. RESULTS: The central CCK release was
      impaired in response to the higher concentration of KCl, and the peripheral CCK
      response to the highest dose of neuromedin C was impaired in old male rats.
      However, no aging effect was observed in female rats, and ovariectomy did not
      affect CCK release or CCK mRNA level. CONCLUSIONS: CCK release from both central
      and peripheral tissues was decreased in old male rats, but not in old female
      rats.

PMID- 9008666
TI  - A randomized controlled trial of progressive resistance training in depressed
      elders.
AB  - BACKGROUND: Depression in elderly people may be contributed to by the multiple
      losses of aging. Exercise has the potential to positively impact many of these
      losses simultaneously. We tested the hypothesis that progressive resistance
      training (PRT) would reduce depression while improving physiologic capacity,
      quality of life, morale, function and self-efficacy without adverse events in an
      older, significantly depressed population. METHODS: We conducted a 10-week
      randomized controlled trial of volunteers aged 60 and above with major or minor
      depression or dysthymia. Subjects were randomized for 10 weeks to either a
      supervised PRT program three times a week or an attention-control group. RESULTS:
      A total of 32 subjects aged 60-84, mean age 71.3 +/- 1.2 yr, were randomized and
      completed the study. No significant adverse events occurred. Median compliance
      was 95%. PRT significantly reduced all depression measures (Beck Depression
      Inventory in exercisers 21.3 +/- 1.8 to 9.8 +/- 2.4 versus controls 18.4 +/- 1.7
      to 13.8 +/- 2, p = .002; Hamilton Rating Scale of Depression in exercisers 12.3
      +/- 0.9 to 5.3 +/- 1.3 versus controls 11.4 +/- 1.0 to 8.9 +/- 1.3, p = .008).
      Quality of life subscales of bodily pain (p = .001), vitality (p = .002), social
      functioning (p = .008), and role emotional (p = .02) were all significantly
      improved by exercise compared to controls. Strength increased a mean of 33% +/-
      4% in exercisers and decreased 2% +/- 2% in controls (p < .0001). In a multiple
      stepwise regression model, intensity of training was a significant independent
      predictor of decrease in depression scores (r2 = .617, p = .0002). CONCLUSIONS:
      PRT is an effective antidepressant in depressed elders, while also improving
      strength, morale, and quality of life.

PMID- 9008665
TI  - Gender differences in the comparison of self-reported disability and performance
      measures.
AB  - BACKGROUND: Gender differences in functioning among older adults have been well
      documented. Differential reporting of functional problems by men and women may
      contribute to this observed difference. The purpose of this study was to examine
      the gender differences in functional ability by comparing self-reported function
      to observed performance of physical tasks. METHODS: In 1988, 1,458 men and women
      ages 71 and older from the New Haven site of the Established Populations for the
      Epidemiologic Study of the Elderly (EPESE) self-reported activities of daily
      living (ADL) disability and functional limitations. Subjects' ability to perform
      7 tasks was observed. Gender differentials in "accurate" and "inaccurate"
      reporting were determined by examining comparable self-reports and performance
      measures. Logistic regression determined how much of the gender differential in
      self-reported function was explained by performance ability. RESULTS: More women
      than men reported disability and functional limitation, and women had poorer
      performance scores for every task. Compared to similar performance items, self
      reports of function were accurate for the majority of men and women. However,
      among those who inaccurately reported function, more men than women underreported
      disability and more women than men overreported disability. Overall performance
      explains all of the gender difference in ADL disability and most of the
      difference in functional limitation. CONCLUSIONS: These results suggest that both
      men and women generally report their disability accurately, and women's higher
      prevalence of reported functional problems is probably a reflection of true
      disability for most disability measures.

PMID- 9008668
TI  - Determinants of patient adherence to consultative comprehensive geriatric
      assessment recommendations.
AB  - BACKGROUND: In consultative models of Comprehensive Geriatric Assessment (CGA),
      lack of implementation of CGA recommendations is well documented and appears to
      be a potential explanation for negative findings. The purpose of this study is to
      identify patient determinants of adherence to recommendations received from a
      community-based CGA consultative model program. METHODS: Subjects (N = 139)
      received self-care and/or physician-initiated CGA recommendations and were
      interviewed three months later to determine adherence with the most important
      recommendation, and health belief, communication, and social support factors
      associated with adherence. Independent variables were organized into the Andersen
      Behavioral Model for analysis. RESULTS: At the bivariate level, one predisposing
      factor (intention) and six enabling factors (low difficulty level, high support,
      high utility, high self-efficacy, agreement on the importance of the
      recommendation and good specific communication about the recommendation) were
      significant determinants of adherence. Two functional health measures and
      seriousness of the target condition of the recommendation were significant need
      factors. In the final logistic regression model, one predisposing variable
      (intention), one enabling variable (utility), and one need factor (high
      functional status), and two interaction terms significantly predicted adherence.
      CONCLUSION: CGA recommendations that are seen as worthwhile, not too much
      trouble, and able to be accomplished are the most likely to be initiated. Older
      adults with relatively higher functional levels are also more likely to follow
      through with CGA recommendations even though their needs may be lower. We found
      the Andersen Behavioral Model useful in the analysis of factors associated with
      adherence behavior to consultative CGA recommendations.

PMID- 9008667
TI  - Dopaminergic responses in the Fischer 344 rat heart: preserved chronotropic and
      dromotropic responses with aging.
AB  - BACKGROUND: Marked decreases in cardiac responses to beta-adrenergic stimuli have
      been found in cellular, animal, and human models of physiologic aging. As another
      probe of receptor-regulated cardiovascular changes with aging, responses to
      dopamine were studied. Responses were studied with and without depletion of
      myocardial catecholamines to eliminate effects secondary to myocardial
      catecholamine release. METHODS: Responses of heart rate (A-A intervals),
      atrioventricular conduction (AV intervals and AV Wenckebach block cycle length)
      to 0-50 microM dopamine were studied in Langendorff perfused hearts from 10
      mature (6.2 +/- 0.8 mo, mean +/- SD) and 9 senescent (23.6 +/- 0.7 mo) Fischer
      344 rats and in hearts from 10 mature (5.3 +/- 0.4 mo) and 8 senescent (23.9 +/-
      0.8) Fischer 344 rats after myocardial catecholamine depletion by reserpine (0.25
      mg/kg i.p. x 5 days). RESULTS: Dopamine decreased A-A (p < .0001) and AV
      conduction intervals (p < .0001) and increased peak developed pressure (p <
      .0001) and dP/dt (p < .001) in hearts from nonreserpine treated mature and
      senescent rats. Greater decreases in A-A intervals and AV conduction were seen in
      senescent compared to mature hearts (p < .0001). Contractile responses were
      greater in mature hearts (p < .001). After reserpine, A-A interval and paced AV
      conduction dose vs response relationships shifted rightward (p < .0001), but peak
      responses and age-related differences in responses were not significantly
      affected. In contrast, increases in peak developed pressure were greatly reduced
      in mature hearts (p < .0001) and age-related differences in contractile responses
      to dopamine were eliminated in hearts from reserpine-treated rats. CONCLUSIONS:
      (a) A-A interval and AV conduction responses to dopamine were greater in
      senescent hearts even after catecholamine depletion, suggesting age-related
      differences in sinus and AV nodal responses to direct dopaminergic stimuli exist.
      (b) Age-related differences in contractile responses to dopamine were eliminated
      by reserpine suggesting basal age-related differences in response were secondary
      to age-related differences in responses to myocardial catecholamine release.

PMID- 9008669
TI  - Reliability of physical performance measures in nursing home residents with
      Alzheimer's disease.
AB  - BACKGROUND: Investigation of the effects of exercise on frail, institutionalized
      individuals with dementia has been impeded by concerns about the reliability of
      physical performance measures when used in this population. METHODS: The physical
      performance of 33 institutionalized subjects with Alzheimer's disease was
      measured during both the morning and afternoon of day 1 by rater 1 and during
      both the morning and afternoon of day 2, one week later, by rater 1 and rater 2.
      Intraclass correlation coefficients (ICCs) were calculated to examine the inter-
      and intrarater reliability of "sit to stand," "25-foot walk," and "the distance
      walked in 6 minutes" and walking speed over 25 feet and for 6 minutes. An
      analysis of variance was performed to determine the components of variance for
      each test. RESULTS: ICCs for "distance walked in 6 minutes" ranged from .80 to
      .99 with 77% of the variance explained by inter-subject difference. The ICCs for
      "time to walk 25 feet" ranged from .57 to .97 with 25% of the variance explained
      by inter-subject differences. In contrast, the "sit to stand" measure produced
      ICCs ranging from -.07 to .85 with only 7% of the variance explained by inter
      subject differences in this impaired population. CONCLUSION: Our results support
      the contention that some physical performance measures can be used to test
      individuals in the later stages of Alzheimer's disease given appropriate
      modification. Although subjects with Alzheimer's disease may have difficulty
      following commands and/or require physical assistance, this does not prohibit the
      reliable assessment of physical performance if measurements are made over longer
      (6-minute walk) rather than shorter periods (25-foot walk).

PMID- 9008670
TI  - Ethnic differences in insulin resistance and its consequences in older Mexican
      American and non-Hispanic white women.
AB  - BACKGROUND: This study was initiated to test the hypothesis that older, healthy,
      nondiabetic Mexican American women would be relatively resistant to insulin
      mediated glucose disposal, hyperinsulinemic, and dyslipidemic as compared to a
      matched group of non-Hispanic White (NHW) women. METHODS: The study, cross
      sectional in nature, involved 14 Mexican American and 19 NHW healthy,
      normotensive nondiabetic, postmenopausal women of similar age and body mass
      index. It took place in the General Clinical Research Center at Stanford Medical
      Center. Measurements were made of fasting plasma glucose, insulin and lipid
      concentrations, and plasma glucose and insulin concentrations following a 75 gram
      oral glucose challenge. Resistance to insulin-mediated glucose disposal was
      estimated by the steady-state plasma glucose (SSPG) concentration achieved at the
      end of a 3-hour constant infusion of glucose, insulin, and somatostatin. RESULTS:
      Mexican American women had significantly greater glucose (p < .001) and insulin
      (p < .001) responses to the oral glucose challenge than did the NHW women.
      Resistance to insulin-mediated glucose disposal was increased in Mexican American
      women (SSPG 195 +/- 25 mg/dl compared to 137 +/- 18 mg/dl in NHW; p < .001).
      While total cholesterol, low density lipoprotein (LDL)-cholesterol, and
      triglyceride concentrations were not significantly different in the two ethnic
      groups, high density lipoprotein (HDL)-cholesterol was significantly lower in the
      Mexican American women (51 mg/dl vs 61 mg/dl; p = .04). CONCLUSION: Older Mexican
      American women are more insulin resistant, glucose intolerant, and
      hyperinsulinemic, and have a lower HDL-cholesterol than a matched group of non
      Hispanic White peers. These results were observed despite the exclusion of
      individuals with non-insulin dependent diabetes mellitus (NIDDM).

PMID- 9008671
TI  - Social support, depression, and activities of daily living in older heart surgery
      patients.
AB  - A theoretical model that specifies relationships among depression, ADL
      impairment, and social support components was tested using 147 patients age 55
      and older undergoing open heart surgery for angina pectoris or aortic stenosis.
      Patients completed interviews and self-reports before surgery and one and 6
      months after surgery. The longitudinal data were analyzed using covariance
      structure modeling techniques. Consistent with an initially theorized structural
      model, the number of close network members seen regularly before surgery was
      associated with perceived adequacy of support one month after surgery. In turn,
      perceived adequacy of support one month after surgery predicted less depression
      and less ADL impairment at 6 months. The number of close network members seen
      regularly was also directly associated with less ADL at one month and less
      depression at 6 months after surgery.

PMID- 9008672
TI  - Wisdom and life satisfaction in old age.
AB  - According to previous research findings, objective life conditions such as
      physical health, socioeconomic status, financial situation, the physical
      environment, and social involvement cannot fully explain the well-being of older
      persons. Instead, personality characteristics and developmental influences appear
      to have a stronger impact. This study combines personality and individual
      development by introducing the ancient but neglected concept of wisdom as a
      predictor of life satisfaction. Using a sample of 120 elderly women and men from
      the 1968/69 Berkeley Guidance Study, structural equation models with latent
      variables show that wisdom (defined aa a composite of cognitive, reflective, and
      effective qualities) has a profoundly positive influence on life satisfaction
      independent of objective circumstances. The inclusion of wisdom as an additional
      predictor of subjective well-being increases the explanatory power of the model
      considerably. Gender differences in predictors of life satisfaction are
      discussed.

PMID- 9008673
TI  - Patterns of motor impairement in normal aging, mild cognitive decline, and early
      Alzheimer's disease.
AB  - In order to determine the relationship between cognitive dysfunction and motor
      behavior in older adults, 41 cognitively normal elderly (NL), 25 cases exhibiting
      mild cognitive impairment (MI), and 25 patients with mild Alzheimer's disease
      (AD) were examined using a broad array to motor/psychomotor and cognitive tests.
      Relative to the NL group, MI individuals (at risk for future decline to AD)
      performed worse on tasks involving fine and complex motor function (e.g.,
      tracking and manual dexterity). AD patients also exhibited motor dysfunction on
      tasks assessing relatively more rudimentary motor control. Motor tasks were able
      to distinguish NL vs MI and NL vs mild AD individuals as effectively as cognitive
      tests of memory and language. These results indicate that motor impairment is an
      important aspect of cognitive decline in older adults. Motor/psychomotor
      assessments may be comparably sensitive to traditional tests of cognitive
      function in identifying persons affected by the earliest stages of AD pathology.

PMID- 9008674
TI  - Age-related differences in movement control: adjusting submovement structure to
      optimize performance.
AB  - In this experiment older and younger adults were compared on their ability to
      position a cursor with an electromechanical mouse. Distance of the movement, size
      of the target, and relative emphasis on the speed or accuracy of the movement
      were manipulated. The study was designed to isolate and evaluate the effects of
      age-related differences in the noise-to-force ratio, perceptual feedback
      efficiency, strategy differences, and the ability to produce force as
      explanations for age-related differences in movement control. This was done by
      using two types of movement tasks and by analyzing movement performance according
      to stages of movement. The study showed that all four factors, when isolated, are
      significantly different for the two age groups. However, in the task component
      where all factors could simultaneously affect performance, the age-related
      difference in performance was less than the difference in either the measure of
      noise-to-force ratio or perceptual efficiency. Analysis of the submovement
      structure revealed how older adults compensated for the greater noise and less
      perceptual efficiency by adjusting the velocity and number of submovements. These
      findings are discussed in light of the optimized submovement model.

PMID- 9008675
TI  - Face and word memory differences are related to patterns of right and left
      lateral ventricle size in healthy aging.
AB  - Discrepancy between face word memory was measured with experimental continuous
      recognition tests and compared with right-left asymmetry of lateral ventricle
      size, measured with volumetric x-ray computed tomography, in 10 young and in 10
      elderly subjects. All were right-handed and healthy. Old subjects differed
      significantly from young subjects on face but not word memory. Old subjects had
      significantly larger lateral ventricles than did young subjects and more lateral
      ventricle asymmetry. No group trend toward disproportionate age-related
      enlargement of the right ventricle relative to the left was noted. In old
      subjects, however, lateral ventricle asymmetry correlated with face-word memory
      discrepancies in the expected direction, worse word than face memory being
      associated with disproportionate enlargement of the left lateral ventricle. These
      correlations were not significant in young subjects. These results suggest that
      the group trend toward disproportionate nonverbal/visual, as opposed to verbal,
      age-related memory differences is not associated with a group trend toward
      disproportionate enlargement of the right ventricle. Individual deviations from
      the normative pattern of age-related ventricle enlargement, however, are
      associated with different patterns of material-specific memory changes.

PMID- 9008676
TI  - Changing perspective on retirement.

PMID- 9008677
TI  - Pathways to labor force exit: work transitions and work instability.
AB  - The purpose of this study is to examine alternative pathways to labor force exit
      among older men. Based on the life course perspective, we distinguish between
      crisp exits from the labor force, which are characterized as being
      unidirectional, and blurred transition patterns, which include repeated exists,
      entrances, and unemployment spells. Using longitudinal data from the 1984 Survey
      of Income and Program Participation, we find that one-quarter of the sample of
      men aged 55 to 74 at first interview experienced at least one transition in labor
      force status over a 28-month observation period. Fewer than half of these can be
      characterized as crisp exists from the labor force. Our multivariate analysis
      suggests that blurred transition patterns are likely part of an effort to
      maintain economic status in later life.

PMID- 9008679
TI  - Social relations and health assessments among older people: do the effects of
      integration and social contributions vary cross-culturally?
AB  - Research on health assessments has shown the importance of social relations as a
      factor influencing health, especially among older people. Drawing upon
      sociological theories of social integration and social exchange, this research
      examines two domains of social relations which are expected to influence assessed
      health. In addition, the study uses a cross-national sample (N = 3,407) of
      noninstitutionalized older people from the Republic of Korea, Fiji, Malaysia, and
      the Philippines to determine if modernization conditions the relationships
      between social relations and health. Results indicate that social integration has
      a positive effect on subjective health assessments in all nations, whereas social
      contributions are significant only in Korea. Findings suggest that health
      assessments by elders in the most modernized nations appear to be much more
      influenced by the contributions they make to the social order than is the case in
      nations which are less modernized.

PMID- 9008678
TI  - Geographic distance and contact between middle-aged children and their parents:
      the effects of social class over 20 years.
AB  - This research derives and tests hypotheses from two alternative conceptual
      models: the modified extended family model, and the changing family constraints
      model, which takes into account recent changes in work and family life. The
      hypotheses address social class differences in geographic distance and contact
      frequency between middle-aged children and their parents over time. Simultaneous
      probit models are used to analyze distance and contact as jointly determined
      outcomes with data from the USC Longitudinal Study of Generations and Mental
      Health. Results from these analyses indicate that children's 1971 educational
      aspirations and social class positions predict 1991 distance and contact between
      generations. Parents who have lower 1991 incomes, however, live farther from
      children and talk with them on the telephone less frequently than higher-income
      parents. Thus, the effects of early social class position support the modified
      extended family model, whereas the effects of current social class position
      support the changing family constraints model.

PMID- 9008680
TI  - Loss to folow-up in a sample of Americans 70 years of age and older: The LSOA
      1984-1990.
AB  - Loss to follow-up is a problem in longitudinal samples, and the literature on
      response rates in panels of older persons suggests that they may be more
      vulnerable to nonrandom attrition and its consequent biases. The event history
      approach used in this study to determine the correlates of nonresponse addresses
      important shortcomings of previous analyses by incorporating time-varying
      covariates. Nonresponse is not random; persons of older ages, lower education,
      who live alone, rent (not own), have more functioning impairments, or have
      another sample person in the household are more likely to become nonrespondents.
      However, correction accounting for the effect of these correlates of nonresponse,
      as well as unobserved characteristics potentially affecting nonresponse, suggests
      that the association between these characteristics and the probability of
      nonresponse is not large enough to introduce bias. While these results are not
      portable to other analyses or panels, they do indicate that in this case,
      significant nonrandom nonresponse does not bias all related analytic results.

PMID- 9008682
TI  - Olanzapine for schizophrenia.

PMID- 9008681
TI  - The quality of health data obtained in a new survey of elderly Americans: a
      validation study of the proposed Medicare Beneficiary Health Status Registry
      (MBHSR).
AB  - The Medicare Beneficiary Health Status Registry (MBHSR) is a proposed new survey
      program that would collect health status indicators annually from large
      probability samples of Medicine beneficiaries. For reasons of economy, the MBHSR
      would use mail survey procedures with telephone follow-up of nonrespondents.
      Because of concerns about response rates and the validity and reliability of the
      data obtained by such methods, a large-scale (N = 1,922) field test was
      conducted. The field test assessed the validity of MBHSR survey reports of past
      medical treatment and conditions by comparing those reports with Medicare claims
      data. It assessed the (internal) reliability of MBHSR survey responses by
      comparing responses with logically related survey questions from the MBHSR.
      Analyses indicate that the MBHSR survey procedures using a combination of mail
      data collection with telephone follow-up of nonrespondents produced relatively
      high levels of sensitivity and specificity in identifying medical treatments and
      procedures previously recorded in Medicare claims data. In addition, the MBHSR
      Field Test obtained, in general, relatively high levels of internal consistency
      in survey reports.

PMID- 9008683
TI  - Drugs for head lice.

PMID- 9008684
TI  - Irinotecan for metastatic colorectal cancer.

PMID- 9008685
TI  - Postgraduate Medicine earns the gold.

PMID- 9008686
TI  - There's no place like home.

PMID- 9008687
TI  - Satisfying the healthcare 'customer'.

PMID- 9008688
TI  - Causes of congestive heart failure. Prompt diagnosis may affect prognosis.
AB  - Congestive heart failure (CHF) is a progressive disease with multiple possible
      causes. Systolic heart failure, defined as contractile failure of the myocardium
      leading to a reduced ejection fraction, is the most common type. Systolic heart
      failure may result from coronary artery disease, hypertension, a metabolic
      disorder, infection, or an infiltrative or other disease, or it may be
      idiopathic. Recognition of CHF can be difficult, especially in elderly patients
      with several medical conditions. An early clinical sign may be dyspnea on
      exertion. The extent of workup needed is often indicated by findings on history
      taking and physical examination. In all patients suspected of having new-onset
      CHF, a chest film, an electrocardiogram, and left ventricular ejection fraction
      should be obtained and a search for complicating and causative factors
      undertaken. Early treatment may halt the otherwise inevitable decline in cardiac
      function and improve prognosis.

PMID- 9008689
TI  - Diastolic heart failure. What primary care physicians need to know.
AB  - Congestive heart failure (CHF) with normal left ventricular systolic function and
      abnormal diastolic performance is a common clinical entity. Typically, signs and
      symptoms are indistinguishable from those of heart failure related to systolic
      dysfunction. Coronary artery disease, systemic hypertension, and aging are all
      associated with diastolic CHF. Diagnosis depends on a clinical suspicion of heart
      failure, followed by assessment of left ventricular systolic performance, which
      is normal in this condition. Ventricular diastolic performance can be assessed by
      noninvasive procedures, the most reliable and easily performed of which is
      echocardiography. General guidelines include searching for precipitants such as
      ischemia, tachycardia, and loss of atrial-ventricular synchrony. Treatment
      includes judicious use of nitrates and diuretics to relieve pulmonary congestion.
      There is no specific therapy to improve left ventricular diastolic function
      directly. However, calcium channel blockers and beta blockers are beneficial, and
      there is growing evidence that angiotensin-converting enzyme inhibitors may prove
      valuable.

PMID- 9008691
TI  - Acute congestive heart failure. The need for aggressive therapy.
AB  - Immediate management of congestive heart failure (CHF) is directed at reduction
      of preload and afterload and augmentation of forward blood flow and cardiac
      output. A variety of pharmacologic agents (e.g., diuretics, positive inotropic
      agents, vasodilators, vasopressors) are available for use in the intensive care
      unit. For patients in cardiogenic shock after acute myocardial infarction,
      pharmacologic measures coupled with direct reperfusion therapy using percutaneous
      revascularization can be lifesaving. Unfortunately, many survivors of acute CHF
      require longterm therapy. Current drug therapy cannot cure CHF, but a search for
      useful and safe oral positive inotropic agents continues, with the hope of
      improving both the quantity and quality of patients' lives. Heart transplantation
      is an alternative for some patients with severe ventricular dysfunction.

PMID- 9008690
TI  - Drug therapy for congestive heart failure. Appropriate choices can prolong life.
AB  - The goals of therapy for congestive heart failure (CHF) are to improve quality of
      life and to prolong it. Improvement in patients with CHF can only be realized,
      however, if a multidisciplinary healthcare team can provide effective management
      in both the inpatient and outpatient settings. Inhibition of compensatory
      mechanisms that perpetuate CHF is the first step in achieving treatment goals.
      Combination therapy with diuretics, digoxin (Lanoxicaps, Lanoxin), and
      vasodilators is used for patients with symptomatic heart failure and volume
      overload. Because angiotensin-converting enzyme inhibitors improve survival rates
      more than other vasodilators, they are preferred in patients with systolic
      dysfunction.

PMID- 9008692
TI  - Antibiotics: past, present, and future. Unearthing nature's magic bullets.

PMID- 9008693
TI  - Osteoporosis. Current pharmacologic options for prevention and treatment.
AB  - For virtually all asymptomatic postmenopausal women, moderate exercise and
      supplementation with calcium and vitamin D are recommended. In addition, most
      postmenopausal women without contraindications would benefit from estrogen
      replacement therapy, primarily because of its cardiovascular benefits. In
      patients with contraindications or an aversion to hormone therapy, bone
      densitometry should be performed to determine risks before expensive nonhormonal
      treatment is initiated. Therapy with alendronate sodium (Fosamax) or calcitonin
      (Calcimar, Miacalcin) is clearly indicated in women with established osteoporosis
      and may be appropriate for early postmenopausal women with osteopenia. Calcitonin
      is a good option in patients with disabling spinal bone pain. Slow-release sodium
      fluoride, although still considered experimental, may eventually be given for
      vertebral fracture in patients with mild to moderate disease.

PMID- 9008694
TI  - Panic disorder. When symptoms have no apparent physical cause.
AB  - Patients with undiagnosed panic disorder often have symptoms of several
      associated physical and social problems, and they frequently seek help initially
      from their primary care physician. Therefore, it is important to be knowledgeable
      in diagnosis and treatment of panic disorder and to consider it in differential
      diagnosis in patients reporting nonpsychiatric complaints. Although the
      underlying pathophysiology of panic disorder is still unclear, current research
      suggests that an imbalance of several neurotransmitter systems may be
      responsible. Many effective cognitive, behavioral, and pharmacologic methods are
      available, and patients may require a combination of approaches. Selective
      serotonin reuptake inhibitors are emerging as first-line therapy because of their
      demonstrated efficacy and tolerability. Tricyclic antidepressants and monoamine
      oxidase inhibitors also have been used successfully, and high-potency benzo
      diazepines are an option when rapid onset of drug activity is desired. Effective
      treatment of panic disorder can significantly decrease hospitalizations, reduce
      unnecessary healthcare expenditures, and improve patient quality of life.

PMID- 9008695
TI  - Emergency treatment of migraine. Insights into current options.
AB  - The physician confronted with a headache patient in acute distress must establish
      the diagnosis before initiating therapy. Although the typical treatment in the
      emergency department has been to rely on narcotic analgesics, many safer
      alternatives are available. With all these therapeutic options to choose from,
      fewer patients should run the risk of narcotic addiction because of migraine
      attacks. To prevent a patient from becoming a frequent emergency department
      visitor, referral for prophylactic treatment is essential.

PMID- 9008696
TI  - Strategies for preventing type II diabetes. What can be done to stem the
      epidemic?
AB  - Non-insulin-dependent (type II) diabetes is a major target for prevention because
      of its staggering emotional and financial burdens on society. The theory behind
      preventive efforts is that individuals at high risk often show signs of impaired
      glucose tolerance before diabetes fully develops. Once identified, these patients
      may respond to several pharmacologic and nonpharmacologic interventions that
      lower blood glucose levels and improve cardiovascular fitness with few adverse
      effects. However, the long-term efficacy of these approaches is uncertain.
      Information from the National Institutes of Health Diabetes Prevention Program
      should help clarify the impact of preventive measures and their cost
      effectiveness.

PMID- 9008697
TI  - Management of ascites. Paracentesis as a guide.
AB  - All patients with new-onset ascites or with known ascites and any change in their
      condition, such as the appearance of fever, abdominal pain, renal insufficiency,
      or encephalopathy, should undergo diagnostic paracentesis to characterize the
      ascitic fluid, detect infection, and aid differential diagnosis. A serum-ascites
      albumin gradient greater than 1.1 g/dL indicates portal hypertension. Spontaneous
      bacterial peritonitis is a common and serious complication of ascites and is best
      diagnosed by the number of neutrophils in the ascitic fluid. Patients with the
      condition should be treated with parenteral antibiotics, and response to therapy
      should be assessed with repeated paracentesis. Hospitalized patients with low
      protein ascites should receive antibiotic prophylaxis. Sodium restriction and
      diuretics are the cornerstones of therapy for ascites. In refractory cases,
      alternative forms of therapy, such as large-volume paracentesis, peritoneovenous
      shunting, or transjugular intrahepatic portosystemic shunting, may be of benefit.
      Patients with refractory ascites should be considered for liver transplantation.

PMID- 9008698
TI  - Sore throat after sore throat after sore throat. Are you asking the critical
      questions?
AB  - In this discussion of recurrent group A streptococcal tonsillopharyngitis, the
      author notes that even at the peak of the streptococcal infection season, not
      more than 30% to 40% of children with sore throats actually have group A
      streptococci as the cause. Thus, it is vital to confirm clinical diagnosis of
      group A streptococcal tonsillopharyngitis with laboratory tests. When patients
      have recurrent infections with group A streptococci, possible causes include
      noncompliance, bacterial resistance, repeated exposure, alteration of the
      throat's microbial ecology, suppression of antibody response due to previous
      antibiotic therapy, and treatment failure. When noncompliance is an issue, an
      injection of penicillin G benzathine may be appropriate. In other circumstances,
      pharmacologic options for treatment of recurrent group A streptococcal
      tonsillopharyngitis include macrolides, clindamycin hydrochloride, rifampin (in
      combination with a second agent), and oral cephalosporins. If a patient has six
      or seven recurrences over 1 or 2 years despite antibiotic treatment,
      tonsillectomy should be considered.

PMID- 9008699
TI  - A functional interaction between the carboxy-terminal domain of RNA polymerase II
      and pre-mRNA splicing.
AB  - In the preceding study we found that Sm snRNPs and SerArg (SR) family proteins co
      immunoprecipitate with Pol II molecules containing a hyperphosphorylated CTD (Kim
      et al., 1997). The association between Pol IIo and splicing factors is maintained
      in the absence of pre-mRNA, and the polymerase need not be transcriptionally
      engaged (Kim et al., 1997). The latter findings led us to hypothesize that a
      phosphorylated form of the CTD interacts with pre-mRNA splicing components in
      vivo. To test this idea, a nested set of CTD-derived proteins was assayed for the
      ability to alter the nuclear distribution of splicing factors, and to interfere
      with splicing in vivo. Proteins containing heptapeptides 1-52 (CTD52), 1-32
      (CTD32), 1-26 (CTD26), 1-13 (CTD13), 1-6 (CTD6), 1-3 (CTD3), or 1 (CTD1) were
      expressed in mammalian cells. The CTD-derived proteins become phosphorylated in
      vivo, and accumulate in the nucleus even though they lack a conventional nuclear
      localization signal. CTD52 induces a selective reorganization of splicing factors
      from discrete nuclear domains to the diffuse nucleoplasm, and significantly, it
      blocks the accumulation of spliced, but not unspliced, human beta-globin
      transcripts. The extent of splicing factor disruption, and the degree of
      inhibition of splicing, are proportional to the number of heptapeptides added to
      the protein. The above results indicate a functional interaction between Pol II's
      CTD and pre-mRNA splicing.

PMID- 9008700
TI  - Splicing factors associate with hyperphosphorylated RNA polymerase II in the
      absence of pre-mRNA.
AB  - The carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II
      (Pol II) contains multiple tandem copies of the consensus heptapeptide,
      TyrSerProThrSerProSer. Concomitant with transcription initiation the CTD is
      phosphorylated. Elongating polymerase has a hyperphosphorylated CTD, but the role
      of this modification is poorly understood. A recent study revealed that some
      hyperphosphorylated polymerase molecules (Pol IIo) are nonchromosomal, and hence
      transcriptionally unengaged (Bregman, D.B., L. Du, S. van der Zee, S.L. Warren.
      1995. J. Cell Biol. 129: 287-298). Pol IIo was concentrated in discrete splicing
      factor domains, suggesting a possible relationship between CTD phosphorylation
      and splicing factors, but no evidence beyond immunolocalization data was provided
      to support this idea. Here, we show that Pol IIo co-immunoprecipitates with
      members of two classes of splicing factors, the Sm snRNPs and non-snRNP SerArg
      (SR) family proteins. Significantly, Pol IIo's association with splicing factors
      is maintained in the absence of pre-mRNA, and the polymerase need not be
      transcriptionally engaged. We also provide definitive evidence that
      hyperphosphorylation of Pol II's CTD is poorly correlated with its
      transcriptional activity. Using monoclonal antibodies (mAbs) H5 and H14, which
      are shown here to recognize phosphoepitopes on Pol II's CTD, we have quantitated
      the level of Pol IIo at different stages of the cell cycle. The level of Pol IIo
      is similar in interphase and mitotic cells, which are transcriptionally active
      and inactive, respectively. Finally, complexes containing Pol IIo and splicing
      factors can be prepared from mitotic as well as interphase cells. The experiments
      reported here establish that hyperphosphorylation of the CTD is a good indicator
      of polymerase's association with snRNP and SR splicing factors, but not of its
      transcriptional activity. Most importantly, the present study suggests that
      splicing factors may associate with the polymerase via the hyperphosphorylated
      CTD.

PMID- 9008701
TI  - Chromosomes with two intact axial cores are induced by G2 checkpoint override:
      evidence that DNA decatenation is not required to template the chromosome
      structure.
AB  - Here we report that DNA decatenation is not a physical requirement for the
      formation of mammalian chromosomes containing a two-armed chromosome scaffold. 2
      aminopurine override of G2 arrest imposed by VM-26 or ICRF-193, which inhibit
      topoisomerase II (topo II)-dependent DNA decatenation, results in the activation
      of p34cdc2 kinase and entry into mitosis. After override of a VM-26-dependent
      checkpoint, morphologically normal compact chromosomes form with paired axial
      cores containing topo II and ScII. Despite its capacity to form chromosomes of
      normal appearance, the chromatin remains covalently complexed with topo II at
      continuous levels during G2 arrest with VM-26. Override of an ICRF-193 block,
      which inhibits topo II-dependent decatenation at an earlier step than VM-26, also
      generates chromosomes with two distinct, but elongated, parallel arms containing
      topo II and ScII. These data demonstrate that DNA decatenation is required to
      pass a G2 checkpoint, but not to restructure chromatin for chromosome formation.
      We propose that the chromosome core structure is templated during interphase,
      before DNA decatenation, and that condensation of the two-armed chromosome
      scaffold can therefore occur independently of the formation of two intact and
      separate DNA helices.

PMID- 9008703
TI  - The autophagic and endocytic pathways converge at the nascent autophagic
      vacuoles.
AB  - We used an improved cryosectioning technique in combination with immunogold
      cytochemistry and morphometric analysis to study the convergence of the
      autophagic and endocytic pathways in isolated rat hepatocytes. The endocytic
      pathway was traced by continuous uptake of gold tracer for various time periods,
      up to 45 min, while the cells were incubated in serum-free medium to induce
      autophagy. Endocytic structures involved in fusion with autophagic vacuoles (AV)
      were categorized into multivesicular endosomes (MVE) and vesicular endosomes
      (VE). Three types of AV--initial (AVi), intermediate (AVi/d), and degradative
      (AVd)--were defined by morphological criteria and immunogold labeling
      characteristics of marker enzymes. The entry of tracer into AV, manifested as
      either tracer-containing AV profiles (AV+) or fusion profiles (FP+) between AV
      and tracer-positive endosomal vesicles/vacuoles, was detected as early as 10 min
      after endocytosis. The number of AV+ exhibited an exponential increase with time.
      FP+ between MVE or VE and all three types of AV were observed. Among the 112 FP+
      scored, 36% involved VE. Of the AV types, AVi and AVi/d were found five to six
      times more likely to be involved in fusions than AVd. These fusion patterns did
      not significantly change during the period of endocytosis (15-45 min). We
      conclude that the autophagic and endocytic pathways converge in a multistage
      fashion starting within 10 min of endocytosis. The nascent AV is the most
      upstream and preferred fusion partner for endosomes.

PMID- 9008702
TI  - Transfer of free polymannose-type oligosaccharides from the cytosol to lysosomes
      in cultured human hepatocellular carcinoma HepG2 cells.
AB  - Large, free polymannose oligosaccharides generated during glycoprotein
      biosynthesis rapidly appear in the cytosol of HepG2 cells where they undergo
      processing by a cytosolic endo H-like enzyme and a mannosidase to yield the
      linear isomer of Man5GlcNAc (Man[alpha 1-2]Man[alpha 1-2]Man[alpha 1-3][Man alpha
      1-6]Man[beta 1-4] GlcNAc). Here we have examined the fate of these partially
      trimmed oligosaccharides in intact HepG2 cells. Subsequent to pulse-chase
      incubations with D-[2-3H]mannose followed by permeabilization of cells with
      streptolysin O free oligosaccharides were isolated from the resulting cytosolic
      and membrane-bound compartments. Control pulse-chase experiments revealed that
      total cellular free oligosaccharides are lost from HepG2 cells with a half-life
      of 3-4 h. In contrast use of the vacuolar H+/ATPase inhibitor, concanamycin A,
      stabilized total cellular free oligosaccharides and enabled us to demonstrate a
      translocation of partially trimmed oligosaccharides from the cytosol into a
      membrane-bound compartment. This translocation process was unaffected by
      inhibitors of autophagy but inhibited if cells were treated with either 100
      microM swainsonine, which provokes a cytosolic accumulation of large free
      oligosaccharides bearing 8-9 residues of mannose, or agents known to reduce
      cellular ATP levels which lead to the accumulation of the linear isomer of
      Man5GlcNAc in the cytosol. Subcellular fractionation studies on Percoll density
      gradients revealed that the cytosol-generated linear isomer of Man5GlcNAc is
      degraded in a membrane-bound compartment that cosediments with lysosomes.

PMID- 9008704
TI  - Visualization of the peroxisomal compartment in living mammalian cells: dynamic
      behavior and association with microtubules.
AB  - Peroxisomes in living CV1 cells were visualized by targeting the green
      fluorescent protein (GFP) to this subcellular compartment through the addition of
      a COOH-terminal peroxisomal targeting signal 1 (GFP-PTS1). The organelle dynamics
      were examined and analyzed using time-lapse confocal laser scanning microscopy.
      Two types of movement could be distinguished: a relatively slow, random,
      vibration-like movement displayed by the majority (approximately 95%) of the
      peroxisomes, and a saltatory, fast directional movement displayed by a small
      subset (approximately 5%) of the peroxisomes. In the latter instance, peak
      velocities up to 0.75 micron/s and sustained directional velocities up to 0.45
      micron/s over 11.5 microns were recorded. Only the directional type of motion
      appeared to be energy dependent, whereas the vibrational movement continued even
      after the cells were depleted of energy. Treatment of cells, transiently
      expressing GFP-PTS1, with microtubule-destabilizing agents such as nocodazole,
      vinblastine, and demecolcine clearly altered peroxisome morphology and
      subcellular distribution and blocked the directional movement. In contrast, the
      microtubule-stabilizing compound paclitaxel, or the microfilament-destabilizing
      drugs cytochalasin B or D, did not exert these effects. High resolution confocal
      analysis of cells expressing GFP-PTS1 and stained with anti-tubulin antibodies
      revealed that many peroxisomes were associated with microtubules. The GFP-PTS1
      labeled peroxisomes were found to distribute themselves in a stochastic, rather
      than ordered, manner to daughter cells at the time of mitosis.

PMID- 9008705
TI  - An early stage of membrane fusion mediated by the low pH conformation of
      influenza hemagglutinin depends upon membrane lipids.
AB  - While the specificity and timing of membrane fusion in diverse physiological
      reactions, including virus-cell fusion, is determined by proteins, fusion always
      involves the merger of membrane lipid bilayers. We have isolated a lipid
      dependent stage of cell-cell fusion mediated by influenza hemagglutinin and
      triggered by cell exposure to mildly acidic pH. This stage preceded actual
      membrane merger and fusion pore formation but was subsequent to a low pH-induced
      change in hemagglutinin conformation that is required for fusion. A low pH
      conformation of hemagglutinin was required to achieve this lipid-dependent stage
      and also, downstream of it, to drive fusion to completion. The lower the pH of
      the medium applied to trigger fusion and, thus, the more hemagglutinin molecules
      activated, the less profound was the dependence of fusion on lipids. Membrane
      incorporated lipids affected fusion in a manner that correlated with their
      dynamic molecular shape, a characteristic that determines a lipid monolayer's
      propensity to bend in different directions. The lipid sensitivity of this stage,
      i.e., inhibition of fusion by inverted cone-shaped lysophosphatidylcholine and
      promotion by cone-shaped oleic acid, was consistent with the stalk hypothesis of
      fusion, suggesting that fusion proteins begin membrane merger by promoting the
      formation of a bent, lipid-involving, stalk intermediate.

PMID- 9008706
TI  - Targeting of chitin synthase 3 to polarized growth sites in yeast requires Chs5p
      and Myo2p.
AB  - Chitin is an essential structural component of the yeast cell wall whose
      deposition is regulated throughout the yeast life cycle. The temporal and spatial
      regulation of chitin synthesis was investigated during vegetative growth and
      mating of Saccharomyces cerevisiae by localization of the putative catalytic
      subunit of chitin synthase III, Chs3p, and its regulator, Chs5p.
      Immunolocalization of epitope-tagged Chs3p revealed a novel localization pattern
      that is cell cycle-dependent. Chs3p is polarized as a diffuse ring at the
      incipient bud site and at the neck between the mother and bud in small-budded
      cells; it is not found at the neck in large-budded cells containing a single
      nucleus. In large-budded cells undergoing cytokinesis, it reappears as a ring at
      the neck. In cells responding to mating pheromone, Chs3p is found throughout the
      projection. The appearance of Chs3p at cortical sites correlates with times that
      chitin synthesis is expected to occur. In addition to its localization at the
      incipient bud site and neck, Chs3p is also found in cytoplasmic patches in cells
      at different stages of the cell cycle. Epitope-tagged Chs5p also localizes to
      cytoplasmic patches; these patches contain Kex2p, a late Golgi-associated enzyme.
      Unlike Chs3p, Chs5p does not accumulate at the incipient bud site or neck. Nearly
      all Chs3p patches contain Chs5p, whereas some Chs5p patches lack detectable
      Chs3p. In the absence of Chs5p, Chs3p localizes in cytoplasmic patches, but it is
      no longer found at the neck or the incipient bud site, indicating that Chs5p is
      required for the polarization of Chs3p. Furthermore, Chs5p localization is not
      affected either by temperature shift or by the myo2-66 mutation, however, Chs3p
      polarization is affected by temperature shift and myo2-66. We suggest a model in
      which Chs3p polarization to cortical sites in yeast is dependent on both Chs5p
      and the actin cytoskeleton/Myo2p.

PMID- 9008707
TI  - A role for the actin cytoskeleton of Saccharomyces cerevisiae in bipolar bud-site
      selection.
AB  - Saccharomyces cerevisiae cells select bud sites according to one of two
      predetermined patterns. MATa and MAT alpha cells bud in an axial pattern, and
      MATa/alpha cells bud in a bipolar pattern. These budding patterns are thought to
      depend on the placement of spatial cues at specific sites in the cell cortex.
      Because cytoskeletal elements play a role in organizing the cytoplasm and
      establishing distinct plasma membrane domains, they are well suited for
      positioning bud-site selection cues. Indeed, the septin-containing neck filaments
      are crucial for establishing the axial budding pattern characteristic of MATa and
      MAT alpha cells. In this study, we determined the budding patterns of cells
      carrying mutations in the actin gene or in genes encoding actin-associated
      proteins: MATa/alpha cells were defective in the bipolar budding pattern, but
      MATa and MAT alpha cells still exhibit a normal axial budding pattern. We also
      observed that MATa/alpha actin cytoskeleton mutant daughter cells correctly
      position their first bud at the distal pole of the cell, but mother cells
      position their buds randomly. The actin cytoskeleton therefore functions in
      generation of the bipolar budding pattern and is required specifically for proper
      selection of bud sites in mother MATa/alpha cells. These observations and the
      results of double mutant studies support the conclusion that different rules
      govern bud-site selection in mother and daughter MATa/alpha cells. A defective
      bipolar budding pattern did not preclude an sla2-6 mutant from undergoing
      pseudohyphal growth, highlighting the central role of daughter cell bud-site
      selection cues in the formation of pseudohyphae. Finally, by examining the
      budding patterns of mad2-1 mitotic checkpoint mutants treated with benomyl to
      depolymerize their microtubules, we confirmed and extended previous evidence
      indicating that microtubules do not function in axial or bipolar bud-site
      selection.

PMID- 9008708
TI  - Cell cycle regulation of the replication licensing system: involvement of a Cdk
      dependent inhibitor.
AB  - The replication licensing factor (RLF) is an essential initiation factor that is
      involved in preventing re-replication of chromosomal DNA in a single cell cycle.
      In Xenopus egg extracts, it can be separated into two components: RLF-M, a
      complex of MCM/P1 polypeptides, and RLF-B, which is currently unpurified. In this
      paper we investigate variations in RLF activity throughout the cell cycle. Total
      RLF activity is low in metaphase, due to a lack of RLF-B activity and the
      presence of an RLF inhibitor. RLF-B is rapidly activated on exit from metaphase,
      and then declines during interphase. The RLF inhibitor present in metaphase
      extracts is dependent on the activity of cyclin-dependent kinases (Cdks).
      Affinity depletion of Cdks from metaphase extracts removed the RLF inhibitor,
      while Cdc2/cyclin B directly inhibited RLF activity. In metaphase extracts
      treated with the protein kinase inhibitor 6-dimethylaminopurine (6-DMAP), both
      cyclin B and the RLF inhibitor were stabilized although the extracts
      morphologically entered interphase. These results are consistent with studies in
      other organisms that invoke a key role for Cdks in preventing re-replication of
      DNA in a single cell cycle.

PMID- 9008709
TI  - Caveolin-3 associates with developing T-tubules during muscle differentiation.
AB  - Caveolae, flask-shaped invaginations of the plasma membrane, are particularly
      abundant in muscle cells. We have recently cloned a muscle-specific caveolin,
      termed caveolin-3, which is expressed in differentiated muscle cells. Specific
      antibodies to caveolin-3 were generated and used to characterize the distribution
      of caveolin-3 in adult and differentiating muscle. In fully differentiated
      skeletal muscle, caveolin-3 was shown to be associated exclusively with
      sarcolemmal caveolae. Localization of caveolin-3 during differentiation of
      primary cultured muscle cells and development of mouse skeletal muscle in vivo
      suggested that caveolin-3 is transiently associated with an internal membrane
      system. These elements were identified as developing transverse-(T)-tubules by
      double-labeling with antibodies to the alpha 1 subunit of the dihydropyridine
      receptor in C2C12 cells. Ultrastructural analysis of the caveolin-3-labeled
      elements showed an association of caveolin-3 with elaborate networks of
      interconnected caveolae, which penetrated the depths of the muscle fibers. These
      elements, which formed regular reticular structures, were shown to be surface
      connected by labeling with cholera toxin conjugates. The results suggest that
      caveolin-3 transiently associates with T-tubules during development and may be
      involved in the early development of the T-tubule system in muscle.

PMID- 9008710
TI  - Newt myotubes reenter the cell cycle by phosphorylation of the retinoblastoma
      protein.
AB  - Withdrawal from the cell cycle is an essential aspect of vertebrate muscle
      differentiation and requires the retinoblastoma (Rb) protein that inhibits
      expression of genes needed for cell cycle entry. It was shown recently that
      cultured myotubes derived from the Rb-/- mouse reenter the cell cycle after serum
      stimulation (Schneider, J.W., W. Gu, L. Zhu, V. Mahdavi, and B. Nadal-Ginard.
      1994. Science (Wash. DC). 264:1467-1471). In contrast with other vertebrates,
      adult urodele amphibians such as the newt can regenerate their limbs, a process
      involving cell cycle reentry and local reversal of differentiation. Here we show
      that myotubes formed in culture from newt limb cells are refractory to several
      growth factors, but they undergo S phase after serum stimulation and accumulate
      4N nuclei. This response to serum is inhibited by contact with mononucleate
      cells. Despite the phenotypic parallel with Rb-/- mouse myotubes, Rb is expressed
      in the newt myotubes, and its phosphorylation via cyclin-dependent kinase 4/6 is
      required for cell cycle reentry. Thus, the postmitotic arrest of urodele
      myotubes, although intact in certain respects, can be undermined by a pathway
      that is inactive in other vertebrates. This may be important for the regenerative
      ability of these animals.

PMID- 9008711
TI  - Regulation of flagellar dynein by phosphorylation of a 138-kD inner arm dynein
      intermediate chain.
AB  - One of the challenges in understanding ciliary and flagellar motility is
      determining the mechanisms that locally regulate dynein-driven microtubule
      sliding. Our recent studies demonstrated that microtubule sliding, in
      Chlamydomonas flagella, is regulated by phosphorylation. However, the regulatory
      proteins remain unknown. Here we identify the 138-kD intermediate chain of inner
      arm dynein I1 as the critical phosphoprotein required for regulation of motility.
      This conclusion is founded on the results of three different experimental
      approaches. First, genetic analysis and functional assays revealed that
      regulation of microtubule sliding, by phosphorylation, requires inner arm dynein
      I1. Second, in vitro phosphorylation indicated the 138-kD intermediate chain of
      I1 is the only phosphorylated subunit. Third, in vitro reconstitution
      demonstrated that phosphorylation and dephosphorylation of the 138-kD
      intermediate chain inhibits and restores wild-type microtubule sliding,
      respectively. We conclude that change in phosphorylation of the 138-kD
      intermediate chain of I1 regulates dynein-driven microtubule sliding. Moreover,
      based on these and other data, we predict that regulation of I1 activity is
      involved in modulation of flagellar waveform.

PMID- 9008712
TI  - Phosphoregulation of an inner dynein arm complex in Chlamydomonas reinhardtii is
      altered in phototactic mutant strains.
AB  - To gain a further understanding of axonemal dynein regulation, mutant strains of
      Chlamydomonas reinhardtii that had defects in both phototactic behavior and
      flagellar motility were identified and characterized. ptm1, ptm2, and ptm3 mutant
      strains exhibited motility phenotypes that resembled those of known inner dynein
      arm region mutant strains, but did not have biochemical or genetic phenotypes
      characteristic of other inner dynein arm mutations. Three other mutant strains
      had defects in the f class of inner dynein arms. Dynein extracts from the pf9-4
      strain were missing the entire f complex. Strains with mutations in pf9/ida1,
      ida2, or ida3 failed to assemble the f dynein complex and did not exhibit
      phototactic behavior. Fractionated dynein from mia1-1 and mia2-1 axonemes
      exhibited a novel f class inner dynein arm biochemical phenotype; the 138-kD f
      intermediate chain was present in altered phosphorylation forms. In vitro
      axonemal dynein activity was reduced by the mia1-1 and mia2-1 mutations. The
      addition of kinase inhibitor restored axonemal dynein activity concomitant with
      the dephosphorylation of the 138-kD f intermediate chain. Dynein extracts from
      uni1-1 axonemes, which specifically assemble only one of the two flagella,
      contained relatively high levels of the altered phosphorylation forms of the 138
      kD intermediate chain. We suggest that the f dynein complex may be
      phosphoregulated asymmetrically between the two flagella to achieve phototactic
      turning.

PMID- 9008713
TI  - Extracellular fibrillar structure of latent TGF beta binding protein-1: role in
      TGF beta-dependent endothelial-mesenchymal transformation during endocardial
      cushion tissue formation in mouse embryonic heart.
AB  - Transforming growth factor-beta (TGF beta) is a dimeric peptide growth factor
      which regulates cellular differentiation and proliferation during development.
      Most cells secrete TGF beta as a large latent TGF beta complex containing mature
      TGF beta, latency associated peptide, and latent TGF beta-binding protein (LTBP)
      1. The biological role of LTBP-1 in development remains unclear. Using a
      polyclonal antiserum specific for LTBP-1 (Ab39) and three-dimensional collagen
      gel culture assay of embryonic heart, we examined the tissue distribution of LTBP
      1 and its functional role during the formation of endocardial cushion tissue in
      the mouse embryonic heart. Mature TGF beta protein was required at the onset of
      the endothelial-mesenchymal transformation to initiate endocardial cushion tissue
      formation. Double antibody staining showed that LTBP-1 colocalized with TGF beta
      1 as an extracellular fibrillar structure surrounding the endocardial cushion
      mesenchymal cells. Immunogold electronmicroscopy showed that LTBP-1 localized to
      40-100 nm extracellular fibrillar structure and 5-10-nm microfibrils. The anti
      LTBP-1 antiserum (Ab39) inhibited the endothelial-mesenchymal transformation in
      atrio-ventricular endocardial cells cocultured with associated myocardium on a
      three-dimensional collagen gel lattice. This inhibitory effect was reversed by
      administration of mature TGF beta proteins in culture. These results suggest that
      LTBP-1 exists as an extracellular fibrillar structure and plays a role in the
      storage of TGF beta as a large latent TGF beta complex.

PMID- 9008716
TI  - Human cell mutagenicity of oxygenated, nitrated and unsubstituted polycyclic
      aromatic hydrocarbons associated with urban aerosols.
AB  - Polycyclic aromatic compounds (PAC) are ubiquitous pollutants in urban air that
      may pose risks to human health. In order to better assess the health risks
      associated with this class of compounds, a total of 67 PAC that either have been
      identified (55) or are suspected to be present (12) in urban aerosol samples were
      tested for mutagenicity in a forward mutation assay based on human B
      lymphoblastoid cells. The cell line used (designated h1A1v2) constitutively
      expresses the cytochrome P4501A1, which is known to be necessary for the
      metabolism of many promutagens. The PAC tested included 39 polycyclic aromatic
      hydrocarbons (PAH). 19 oxygen-containing PAH (oxy-PAH) and nine NO2-substituted
      PAH (nitro-PAH). A total of 26 PAH were mutagenic. In comparing the minimum
      mutagenic concentrations of the mutagenic PAH with that of benzo[a]pyrene (B[a]P)
      it was found that dibenzo[a,l]pyrene (DB[al]P), cyclopenta[c,d]pyrene (CPP),
      naphtho[2,1-a]pyrene, dibenzo[a,e]pyrene (B[a]P) and 1-methylbenzo[a]pyrene were
      24 +/- 21, 6.9 +/- 4.2, 3.2 + 3.0, 2.9 +/- 2.9 and 1.6+/- 1.4 times,
      respectively, more mutagenic than B[a]P, and that dibenzo[a,k]fluoranthene and
      B[a]P were approximately equally mutagenic. The 19 other mutagenic PAH were
      between approximately 2 and approximately 1800 times less mutagenic than B[a]P.
      Of the oxy-PAH tested only phenalenone, 7H-benz[d,e]anthracen-7-one, 3-nitro-6H
      dibenzo[b,d]pyran-6-one, cyclopenta[c,d]pyren-3(4H)-one, 6H-benzo[c,d]pyren-6-one
      (BPK) and anthanthrenequinone were mutagenic; however, with the exception of BPK,
      these were over 50 times less active than B[a]P, BPK was approximately 3 times
      less active than B[a]P. Seven of the nitro-PAH were mutagenic including 9
      nitroanthracene, 1-nitropyrene, 2-nitrofluoranthene, 3-nitrofluoranthene, 1,3
      dinitropyrene, 1,6-dinitropyrene (1,6-DNP) and 1,8-dinitropyrene. 1,6-DNP was
      approximately 4 times less active than B[a]P; the six other mutagenic nitro-PAH
      were between 20 and 380 times less active than B[a]P. These results are discussed
      in terms of their relevance for determining the most important mutagens in
      ambient air. Based on reported concentrations of PAC in ambient aerosols, it is
      possible that CPP, DB[ae]P, DB[al]P and BPK could account for a greater
      proportion of the mutagenicity than B[a]P in some aerosols.

PMID- 9008714
TI  - Bcl-2 lies downstream of parathyroid hormone-related peptide in a signaling
      pathway that regulates chondrocyte maturation during skeletal development.
AB  - Parathyroid hormone-related peptide (PTHrP) appears to play a major role in
      skeletal development. Targeted disruption of the PTHrP gene in mice causes
      skeletal dysplasia with accelerated chondrocyte maturation (Amizuka, N., H.
      Warshawsky, J.E. Henderson, D. Goltzman, and A.C. Karaplis. 1994. J. Cell Biol.
      126:1611-1623; Karaplis, A.C., A. Luz, J. Glowacki, R.T. Bronson, V.L.J.
      Tybulewicz, H.M. Kronenberg, and R.C. Mulligan. 1994. Genes Dev. 8: 277-289). A
      constitutively active mutant PTH/PTHrP receptor has been found in Jansen-type
      human metaphyseal chondrodysplasia, a disease characterized by delayed skeletal
      maturation (Schipani, E., K. Kruse, and H. Juppner. 1995. Science (Wash. DC).
      268:98-100). The molecular mechanisms by which PTHrP affects this developmental
      program remain, however, poorly understood. We report here that PTHrP increases
      the expression of Bcl-2, a protein that controls programmed cell death in several
      cell types, in growth plate chondrocytes both in vitro and in vivo, leading to
      delays in their maturation towards hypertrophy and apoptotic cell death.
      Consequently, overexpression of PTHrP under the control of the collagen II
      promoter in transgenic mice resulted in marked delays in skeletal development. As
      anticipated from these results, deletion of the gene encoding Bcl-2 leads to
      accelerated maturation of chondrocytes and shortening of long bones. Thus, Bcl-2
      lies downstream of PTHrP in a pathway that controls chondrocyte maturation and
      skeletal development.

PMID- 9008717
TI  - Phenethyl isothiocyanate modulates clastogenicity of mitomycin C and
      cyclophosphamide in vivo.
AB  - Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables,
      is an effective chemopreventive agent against N-nitrosamine-induced
      carcinogenesis. We have investigated the extent to which PEITC modulates the
      clastogenicity of standard genotoxicants, mitomycin C and cyclophosphamide, using
      bone marrow cells of Swiss albino mice. PEITC, 1 mumol/kg body weight in corn oil
      was administered by gavage for 7 consecutive days to prime the animals. 24 h
      later, mice received a single dose of cyclophosphamide (10 or 20 mg/kg body
      weight) or mitomycin C (1 or 2 mg/kg body weight) intraperitoneally.
      Clastogenicity of the chemicals was compared using PEITC-primed and non-primed
      animals 24 h after clastogen treatment. As a single agent, PEITC is not
      clastogenic even after 7 days of priming. Oral priming with PEITC decreased the
      aberrations per cell values by 22-67% in all cases. PEITC could only alleviate
      the clastogenicity of 1 mg/kg body weight mitomycin C to near-control values (p <
      or = 0.05). Although PEITC is reported to be effective against N-nitrosamine
      induced tumorigenesis by preventing metabolic activation and by blocking the
      reactive species formed, it is virtually ineffective against the clastogenicity
      of cyclophosphamide. The results of inhibition by PEITC of the clastogenicity of
      mitomycin C suggest that the modulation of mitomycin C bio-activation contributes
      to, but may not be sufficient for, PEITC chemoprevention of clastogenicity by
      mitomycin C.

PMID- 9008718
TI  - Genotoxicity of the laxative drug components emodin, aloe-emodin and danthron in
      mammalian cells: topoisomerase II mediated?
AB  - 1,8-Dihydroxyanthraquinones are under debate as plant-derived carcinogens that
      are found in laxatives, food colors, and possibly vegetables. Published
      genotoxicity data are controversial, and so three of them (emodin, danthron and
      aloe-emodin) were tested in a number of in vitro assay systems. All three
      compounds induced tk-mutations in mouse lymphoma L5178Y cells. Induction of
      micronuclei also occurred in the same cell line, and was dose-dependent, with the
      potency ranking being danthron > aloe-emodin > emodin. In a DNA decatenation
      assay with a network of mitochondrial DNA of C. fasciulata, all three test
      compounds inhibited the topoisomerase II-mediated decatenation. Danthron and aloe
      emodin, but not emodin, increased the fraction of DNA moving into comet tails
      when tested at concentrations around 50 microM in single-cell gel-electrophoresis
      assays (SCGE; comet assay). Comet assays were also used in modified form to
      determine whether pretreatment of the cells with the test compounds would reduce
      the effects of etoposide, a potent topoisomerase II inhibitor. All three test
      chemicals were effective in this pretreatment protocol, with danthron again being
      the most potent. Given clearcut evidence of their genotoxic activity, further
      research on the human cancer risk of these compounds may be warranted.

PMID- 9008719
TI  - Dominant lethal mutations, heritable translocations, and unscheduled DNA
      synthesis induced in male mouse germ cells by glycidamide, a metabolite of
      acrylamide.
AB  - The hypothesis that acrylamide induces dominant lethal mutations and heritable
      translocations in male mice, not through direct adduction, but by conversion to
      the reactive epoxide, glycidamide, was investigated. Three studies, namely,
      induction of dominant lethal mutations, heritable translocations, and unscheduled
      DNA synthesis in spermatids, which were conducted earlier in this laboratory for
      acrylamide, were also performed for glycidamide to determine its mutagenic
      properties and to compare responses. Results of these studies are consistent with
      the proposal that in vivo conversion to glycidamide is responsible for the
      mutagenicity of acrylamide in male mice.

PMID- 9008720
TI  - In vitro mutagenicity and genotoxicity study of 1,2-dichloroethylene, 1,1,2
      trichloroethane, 1,3-dichloropropane, 1,2,3-trichloropropane and 1,1,3
      trichloropropene, using the micronucleus test and the alkaline single cell gel
      electrophoresis technique (comet assay) in human lymphocytes.
AB  - The main objective of this study was to compare the cytotoxic genotoxic and
      mutagenic activity of a number of chlorinated aliphatic hydrocarbons, which are
      widely used as chemical intermediates, solvents, degreasing agents etc. in
      industry, and to establish the structure-toxicity relationship of the chemicals
      by using the most adequate determinants in estimating their toxicity. The
      mutagenicity and cytotoxicity of some of the candidate chemicals, namely 1,2
      dichloroethylene, 1,1,2-trichloroethane, 1,3-dichloropropane, 1,2,3
      trichloropropane and 1,1,3-trichloropropene were evaluated in an in vitro
      micronucleus assay. The cytokinesis-block methodology was applied on human
      lymphocytes in the presence or absence of an external metabolic activation system
      (S9-mix). In the micronucleus assay, all test substances, except 1,2,3
      trichloropropane with and without S9-mix and 1,1,2-trichloroethane without S9-mix
      in the repeated experiment, exhibited a low but statistically significant
      mutagenic activity, compared to the concurrent control. However, none of the five
      chemicals was able to induce a clear and reproducible linear dose-dependent
      increase in micronucleus frequencies in this assay. Generally, mutagenic activity
      of the chemicals was found in the absence of severe cytotoxicity and/or cell
      cycle delay. The DNA breakage capacity and the cytotoxicity of these chemicals
      were also assessed in the alkaline single cell gel (SCG) electrophoresis test
      (comet assay) with and without S9-mix in isolated human lymphocytes. All chemical
      compounds induced DNA breakage, in the presence or absence of the metabolic
      activation system, at the doses tested. The data showed that the DNA reactivity
      of the chemicals increased with increasing degree of halogenation. The results of
      the present work suggested that the comet assay might be a more suitable and
      sensitive screening method than the micronucleus test for this particular class
      of compound. However, both assays do detect different endpoints.

PMID- 9008715
TI  - Inhibition of Ced-3/ICE-related proteases does not prevent cell death induced by
      oncogenes, DNA damage, or the Bcl-2 homologue Bak.
AB  - There is increasing evidence for a central role in mammalian apoptosis of the
      interleukin-1 beta-converting enzyme (ICE) family of cysteine proteases,
      homologues of the product of the nematode "death" gene, ced-3. Ced-3 is thought
      to act as an executor rather than a regulator of programmed cell death in the
      nematode. However, it is not known whether mammalian ICE-related proteases (IRPs)
      are involved in the execution or the regulation of mammalian apoptosis. Moreover,
      an absolute requirement for one or more IRPs for mammalian apoptosis has yet to
      be established. We have used two cell-permeable inhibitors of IRPs, Z-Val-Ala
      Asp.fluoromethylketone (ZVAD.fmk) and t-butoxy carbonyl-Asp.fluoromethylketone
      (BD.fmk), to demonstrate a critical role for IRPs in mammalian apoptosis induced
      by several disparate mechanisms (deregulated oncogene expression, ectopic
      expression of the Bcl-2 relative Bak, and DNA damage-induced cell death). In all
      instances, ZVAD.fmk and BD.fmk treatment inhibits characteristic biochemical and
      morphological events associated with apoptosis, including cleavage of nuclear
      lamins and poly-(ADP-ribose) polymerase, chromatin condensation and nucleosome
      laddering, and external display of phosphatidylserine. However, neither ZVAD.fmk
      nor BD.fmk inhibits the onset of apoptosis, as characterized by the onset of
      surface blebbing; rather, both act to delay completion of the program once
      initiated. In complete contrast, IGF-I and Bcl-2 delay the onset of apoptosis but
      have no effect on the kinetics of the program once initiated. Our data indicate
      that IRPs constitute part of the execution machinery of mammalian apoptosis
      induced by deregulated oncogenes, DNA damage, or Bak but that they act after the
      point at which cells become committed to apoptosis or can be rescued by survival
      factors. Moreover, all such blocked cells have lost proliferative potential and
      all eventually die by a process involving cytoplasmic blebbing.

PMID- 9008721
TI  - Antimutagenicity of Tochu tea (an aqueous extract of Eucommia ulmoides leaves):
      2. Suppressing effect of Tochu tea on the urine mutagenicity after ingestion of
      raw fish and cooked beef.
AB  - The effect of Tochu tea, which is an aqueous extract of Eucommia ulmoides leaves
      and a popular-beverage in Japan, on the urine mutagenicity before and after
      ingestion of raw fish and cooked beef was studied using Salmonella typhimurium
      YG1024. Urines were collected from seven healthy, non-smoking Japanese women
      before and after ingestion of raw fish and cooked beef. In experiment 1,3 were in
      a control group and 4 were in a Tochu tea-drinking group (2000 ml per day). The
      mutagenicity of urine from the Tochu tea-drinking group was much lower. In
      experiment 2 the 7 women switched groups; the tea-drinking group became the
      control group, and the control group became the Tochu tea-drinking group. Again,
      the mutagenicity of urine collected from the Tochu tea-drinking group was much
      lower. These results suggest that the decrease in the mutagenicity of the urine
      from the Tochu tea-drinking group was due to the intake of Tochu tea, but not to
      individual differences. Thus, the ingestion of Tochu tea may reduce human
      exposure to dietary mutagens.

PMID- 9008722
TI  - Mixed disulfides from disulfiram inhibit the benzo[a]pyrene induced mutagenesis.
AB  - Some mixed disulfides derived from disulfiram and endogenous thiol compounds have
      been synthesized, biochemically characterized and their potential antigenotoxic
      effects have been proposed. The present study evaluated the mutagenic and
      antimutagenic specificities of two mixed disulfides using S. typhimurium
      reversion assay, namely S-(N,N-diethyldithiocarbamoyl)-N-acetylcysteine (AC-DDTC)
      and-L-glutathione (GS-DDTC). The two mixed disulfides were not mutagenic to
      Salmonella strains TA98 and TA100 in the presence or absence of S9 mixture. The
      increased number of revertants by benzo[a]pyrene (B(a)P) has been reduced to the
      control level by the preincubation with AC-DDTC or GS-DDTC. It was not due to the
      killing effect of B(a)P, mixed disulfides or B(a)P-disulfide mixture. The
      antimutagenic effect of AC-DDTC was more potent than that of GS-DDTC. These
      results indicate that AC-DDTC and GS-DDTC may have a role to play in reducing the
      risk of mutagenic effects of B(a)P.

PMID- 9008723
TI  - Melatonin and radioprotection from genetic damage: in vivo/in vitro studies with
      human volunteers.
AB  - Peripheral blood samples were collected from human volunteers at 0 (5-10 min
      before), and at 1 and 2 h after a single oral dose of 300 mg of melatonin. At
      each time point, (i) the concentration of melatonin in the serum and in the
      leukocytes was determined, and (ii) the whole blood was exposed in vitro to 150
      cGy of 137Cs gamma radiation, and the lymphocytes were cultured with mitogenic
      stimulation to determine the extent of radiation-induced genetic damage, viz,
      chromosome aberrations and micronuclei. For each volunteer, the results showed a
      significant increase in the concentration of melatonin in the serum and in the
      leukocytes at 1 h after the oral dose of melatonin, as compared to the sample
      collected at 0 h. The lymphocytes in the blood samples collected at 1 and 2 h
      after melatonin ingestion and exposed in vitro to 150 cGy gamma radiation
      exhibited a significant decrease in the incidence of chromosome aberrations and
      micronuclei, as compared with similarly irradiated lymphocytes from the blood
      sample collected at 0 h; the frequencies observed in the cells sampled at 2 h
      after the ingestion of melatonin were consistently lower when compared with those
      collected at 1 h. The data may have important implications for the protection of
      human lymphocytes from the genetic damage induced by free radical-producing
      mutagens and carcinogens.

PMID- 9008724
TI  - Stability of benzo[a]pyrene DNA adducts in rat tissues during their long-term
      storage at -20 degrees C or -80 degrees C.
AB  - The aim of this study was to examine whether the storage of tissues at -80
      degrees C or -20 degrees C affects the benzo[a]pyrene (B[a]P)-derived DNA adduct
      pattern and levels in rat tissues. Three rats were treated orally with a single
      dose of 100 mg B[a]P/kg b.w. and killed 24 h later. White blood cells (WBC) were
      isolated from the fresh blood. Livers, lungs and hearts were immediately removed,
      dissected into small fragments and were pooled for each organ. Pooled samples
      were proportionally divided into 7 aliquots. DNA from the first aliquot was
      immediately isolated (time 0). The other aliquots were frozen and stored at -20
      degrees C or at -80 degrees C. DNA was isolated from the frozen samples at 1, 5
      and 10 months later. 32P-postlabeling analysis was performed at the beginning and
      at the end of study with the whole set of samples. Two B[a]P-derived adducts were
      detected in all tissues but with different intensities for different tissue
      types. One of the adducts was found predominantly in WBC (approximately 85%) and
      liver (approximately 68%), while heart and lung accounted only for approximately
      43% and approximately 39%, respectively. This adduct was tentatively identified
      as benzo[a]pyrene diol-epoxide-N2 adduct (BPDE-N2-dG) based on TLC and HPLC
      analyses of 32P-postlabeled adducts. The highest total DNA adduct level (sum of 2
      spots) was found in lung (4.90 adducts/10(8) nucleotides) compared with heart,
      liver and WBC (3.55, 2.37 and 2.32 adducts/10(8) nucleotides, respectively). The
      analysis of variance provided evidence that storage of tissues at -20 degrees C
      or at -80 degrees C up to 10 months did not significantly affect B[a]P DNA adduct
      levels and patterns in the rat lung, heart and liver. Our study indicates that
      properly stored tissues can be used for DNA adduct analysis with confidence.

PMID- 9008725
TI  - Quantification of epithelial cell micronuclei by fluorescence in situ
      hybridization (FISH) in mortuary science students exposed to formaldehyde.
AB  - A micronucleus assay employing fluorescence in situ hybridization (FISH) with a
      centromeric probe was used on specimens of exfoliated buccal and nasal cells
      collected from mortuary science students exposed to embalming fluid containing
      formaldehyde. FISH labeling allowed micronuclei (MN) containing a whole
      chromosome (centromere-positive, MN+) to be differentiated from those containing
      only chromosomal fragments (centromere-negative, MN-). Each student was sampled
      before and after the 90 day embalming class. We determined if an increase in MN
      frequency could be attributed to formaldehyde exposure and was specific to either
      MN+ or MN-. In buccal cells, total MN frequency was significantly increased from
      0.6/1000 to 2/1000 (p = 0.007) following the course, whereas in nasal cells it
      was not (2 and 2.5/1000, respectively, p = 0.2). Cells with multiple MN were
      present only in samples taken after exposure to embalming fluid. Although the
      baseline frequency was higher for MN+ in both buccal (0.4/1000 for MN+ and
      0.1/1000 for MN-) and nasal cells (1.2/1000 for MN+ and 0.5/1000 for MN-), the
      increase in MN frequency was greater for MN-, (9-fold, p = 0.005 for buccal
      cells; 2-fold, p = 0.03 for nasal cells) than for MN+ (> 2-fold, p = 0.08 for
      buccal cells; no change, p = 0.31 for nasal cells) in both tissues. Thus, the
      primary mechanism of micronucleus formation appeared to be chromosome breakage.
      This finding is consistent with known clastogenic properties of formaldehyde, the
      component of embalming fluid most likely responsible for micronucleus induction.

PMID- 9008726
TI  - Lack of genotoxicity of piperonyl butoxide.
AB  - The genotoxicity of piperonyl butoxide has been investigated in bacterial
      mutation assays using tester strains TA98, TA100, TA1535, TA1537 and TA1538. The
      assays were conducted both with and without metabolic activation. Piperonyl
      butoxide was tested for mutation with and without metabolic activation in the
      CHO/HGPRT assay. Chromosomal aberrations were investigated also using Chinese
      hamster ovary (CHO) cells and effects on DNA were evaluated by in vitro
      unscheduled DNA synthesis (UDS) test using rat liver primary cell cultures.
      Piperonyl butoxide was not shown to be genotoxic in any assay system. The data
      presented supports the view that the liver tumors observed in rodents at dose
      levels above the maximally tolerated dose (MTD) result from a secondary non
      genotoxic mechanism.

PMID- 9008727
TI  - In vivo chromosomal aberrations in bone marrow cells of rats treated with
      Marshal.
AB  - In this study, the cytogenetic effects of Marshal (insecticide/nematocide) were
      investigated in bone marrow cells of rats. The results obtained from animals
      treated with Marshal were compared with the results of animals treated with ethyl
      carbamate (EC) and with controls. Concentrations of 12.5, 25 and 50 mg/kg b.wt.
      of Marshal and 100, 200 and 400 mg/kg b.wt. of EC were used and animals were
      sampled at three different times (6, 12 and 24 h). Marshal increased the number
      of chromosomal aberrations (CA) per cell, and the number of cells with
      abnormalities, at all concentrations and treatment times. Generally, Marshal
      could increase the number of the abnormal cells and the formation of CA as easily
      as EC. However, Marshal, at 50 mg/kg b.wt. did not increase the frequency of
      abnormal cells or CA as strongly as EC, at 400 mg/kg b.wt. for 6 h. Marshal also
      decreased the mitotic index (MI) compared with the control group. The MI was
      higher in the group treated with Marshal for 6 h than that treated with EC.
      However, the effects of Marshal and EC on the MI in the groups treated for 12 and
      24 h were similar. We found that the effect of Marshal on the formation of
      abnormal cells and CA was dependent on concentration and treatment time.

PMID- 9008728
TI  - Identification of a heteromorphic microsatellite within the thymidine kinase gene
      in L5178Y mouse lymphoma cells.
AB  - The objective of this work is to identify a heteromorphism within the thymidine
      kinase (Tk1) gene which can be used to assay for allele loss by means of PCR.
      Intron F of mouse Tk1 contains two (CA)n microsatellite sequences separated by
      107 bp of non-repetitive sequence. We tested this region for heteromorphism in
      L5178Y mouse lymphoma cells. A PCR primer pair designated Agl1 yielded products
      of 396 and 194 bp from L5178Y tk+/- genomic DNA. The 194-bp product resulted from
      a secondary binding site between the two (CA)n repeats for the forward Ag11
      primer and was not produced from tk-/- mutants that had lost the functional Tk1b
      allele. Agl2 primers produced two PCR products of 523 and approximately 440 bp
      and Agl3 primers produced products of 579 and approximately 500 bp. In both these
      cases, the difference in product size was approximately equal, indicating that
      Intron F is approximately 80 bp shorter in the non-functional Tk1a allele than in
      Tk1b. This heteromorphism forms the basis for an assay for allele loss by means
      of PCR. Agl1 and Agl3 primers yielded additional products of 91 and 274 bp,
      respectively, consistent with sizes expected from the mouse Tk1 pseudogenes (Tk1
      ps). Our conclusions drawn from an analysis of 122 mutants for Tk1b loss using
      Agl2 primers agreed with previous analysis of the NcoI heteromorphism. Thus, a
      simple PCR-based analysis can identify Tk1b loss in the L5178Y mouse lymphoma
      cells.

PMID- 9008729
TI  - Lack of effect of piperonyl butoxide on unscheduled DNA synthesis in precision
      cut human liver slices.
AB  - In this study the effect of piperonyl butoxide (PBO) on unscheduled DNA synthesis
      in precision-cut human liver slices has been examined. Liver slices prepared from
      tissue samples from five human donors were cultured in medium containing
      [3H]thymidine and 0-2.5 mM PBO using a dynamic organ culture system. After 24 h
      the liver slices were processed for autoradiographic examination of UDS. As
      positive controls, liver slices were also cultured with three known genotoxic
      agents, namely 2-acetylaminofluorene (2-AAF), aflatoxin B1 (AFB1) and 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). UDS was quantified as the net grain
      count in centrilobular hepatocytes and as the percentage of centrilobular
      hepatocyte nuclei with > 5 and > 10 net grains. Compared to control liver slice
      cultures PBO had no effect on UDS. In contrast, treatment with 0.02 and 0.05 mM 2
      AAF, 0.002 and 0.02 mM AFB1 and 0.005 and 0.05 mM PhIP produced significant
      increases in net grain counts of centrilobular hepatocytes. The greatest
      induction of UDS was observed in liver slices treated with 0.05 mM PhIP.
      Treatment with 2-AAF, AFB1 and PhIP also produced increases in the number of
      centrilobular hepatocyte nuclei with > 5 and > 10 net grains. At the
      concentrations examined neither PBO, 2-AAF nor PhIP had any significant effect on
      replicative DNA synthesis in 24 h cultured human liver slices. In cultured liver
      slices treated with 0.02, but not 0.002, mM AFB1 a significant reduction in the
      rate of replicative DNA synthesis was observed. These results demonstrate that
      PBO does not induce UDS in cultured human liver slices. However, all three
      positive control compounds produced marked significant increases in UDS, thus
      confirming the functional viability of the human liver slice preparations used in
      this study. In conclusion, these results provide further evidence that PBO is a
      non-genotoxic agent which does not damage DNA in human liver.

PMID- 9008730
TI  - Simple and reliable enumeration of micronucleated reticulocytes with a single
      laser flow cytometer.
AB  - A flow cytometric procedure for scoring micronuclei in mouse peripheral blood
      erythrocytes, especially reticulocytes, is described. The methods reported herein
      were developed in an effort to simplify the techniques and to reduce the
      equipment requirements associated with automated micronucleus analyses. With this
      procedure, fluorescein-conjugated monoclonal antibodies which bind to the CD71
      defined antigen (the transferrin receptor) are used to label reticulocytes. The
      nucleic acid dye propidium iodide is used to identify cells with micronuclei.
      Given 488 nm excitation, four populations of erythrocytes are clearly resolved:
      normochromatic erythrocytes with and without micronuclei, and reticulocytes with
      and without micronuclei. Since the method is capable of simultaneously providing
      the incidence of micronuclei in both mature and immature erythrocyte populations,
      it is compatible with either chronic or acute treatment regimens. To demonstrate
      cell handling and flow cytometric procedures for quantitatively analyzing
      peripheral blood micronuclei, an experiment with the model clastogen methyl
      methanesulfonate is described. Additionally, a reconstruction experiment was
      performed whereby three mouse blood samples were spiked with successively greater
      volumes of blood from a clastogen-treated animal so each preparation differed
      slightly, but definitely, in micronucleus content. Each sample was scored six
      times by conventional microscopy and by flow cytometry so that the two methods
      could be directly compared. Collectively, the results from the methyl
      methanesulfonate experiment and the reconstruction study demonstrate the accuracy
      and reliability of the flow cytometric method. Furthermore, advantages associated
      with objective, high throughout scoring methodology are clearly indicated.

PMID- 9008731
TI  - Mutagenicity of dihydroxybenzenes and dihydroxynaphthalenes for Ames Salmonella
      tester strains.
AB  - The mutagenicity of 3 dihydroxybenzene (DHB) and 9 dihydroxynaphthalene (DHN)
      isomers was examined by using 5 different Ames Salmonella mutagenicity tester
      strains in the presence and absence of phenobarbital and 5,6-benzoflavone-treated
      rat liver S9-mix. Of the 3 DHB isomers, 1,4-DHB (hydroquinone) was mutagenic, and
      of the 9 DHN isomers, 1,3-DHN (naphthoresorcinol), 1,4-DHN (hydronaphthoquinone),
      1,6-DHN and 1,7-DHN were mutagenic. Mutagenicity of all the compounds tested was
      observed in the absence of S9-mix, while 1,4-DHN and 1,6-DHN were also mutagenic
      in the presence of S9-mix. The mutagenicity of 1,4-DHB and 1,4-DHN for TA104,
      which is a strain sensitive to oxidative mutagens, was almost completely or
      partially inhibited by superoxide dismutase (SOD) and/or catalase, indicating the
      involvement of activated oxygen species in mutagenesis. Furthermore, from the
      finding that the 4 DHNs were mutagenic for TA2637, the strain sensitive to
      frameshift mutagens, it is possible that the mutagenicity of DHNs for S.
      typhimurium was also attributable to DNA adducts that form with quinones and/or
      semiquinones through oxidation of DHNs. The mutagenicity of 1,3-DHN, which showed
      the largest number of revertants in strains TA100, TA98, TA2637 and TA104, was
      greatly decreased, when their pKM101 plasmid-deficient strains, TA1535, TA1538,
      TA1537 and TA2659 were used. This observation suggests that an SOS repair system
      was involved in the mutagenesis of 1,3-DHN for S. typhimurium.

PMID- 9008733
TI  - Cellular immune response and pathology in schistosomiasis.
AB  - In the present review, some aspects of the cellular response following the murine
      Schistosoma mansoni infection are described. Due to the peculiar route used by
      the schistosome to infect its definitive host, the skin appears as a critical
      site in which the initial events of the host/parasite relationship occur and
      where the immune response is initiated. Moreover, the induction and the
      modulation of the granuloma formation, which represent the main aspect of the
      pathology of this parasitic disease, is under the control of several cellular
      populations n which CD4 and CD8 T cells play a key role. The cytokines produced
      in response to the parasite, such as IL7 in the skin and IFN gamma in the liver,
      seem to influence the further development of immunity against Schistosoma
      mansoni.

PMID- 9008732
TI  - [The chromosome cycle of DNA. 1971].
AB  - A hypothesis on the behaviour of DNA molecules during the cell cycle has been put
      forward using information on the regularities observed in the formation of
      chromosome aberrations while irradiating different stages of the cell cycle. The
      relevant statements of the hypothesis are as follows. 1) The cell cycle involves
      two stages of intermolecular proofs. The first proof occurs before DNA synthesis,
      the second one before mitosis. 2) The probable mechanism of the proofs is
      connected with the formation of hybrid DNA molecules. 3) In the case of
      multistrandedness, the second proof follows a relay-race principle.

PMID- 9008734
TI  - Local immune response to experimental Fasciola hepatica infection in sheep.
AB  - Macrophages, eosinophils, neutrophils and lymphocyte subpopulations (OvCD5+,
      OvCD4+, OvCD8+, OvWC1+ and lg+) were identified in sections of hepatic tissue and
      hepatic lymph nodes from sheep experimentally infected with F. hepatica and
      necropsied 14, 28, 42 or 56 days post infection. The migratory tunnels produced
      by juvenile flukes appeared as local areas of necrosis surrounded by infiltrating
      inflammatory cells, particularly numerous macrophages, eosinophils and OvCD4+
      lymphocytes n addition, B lymphocyte proliferation was observed in hepatic lymph
      nodes and in hepatic portal tracts. Only three juvenile flukes were identified in
      the sections. They where partially in contact with healthy tissue and partially
      with neutrophils, macrophages and eosinophils; they were covered by IgM Host
      parasite interactions resulting from immune response regulation by helper T
      lymphocytes and from immune evasion by the parasite are discussed.

PMID- 9008735
TI  - [Mast cells and eosinophils of the respiratory mucosa of sheep with Oestrus ovis
      (Linne, 1761) infection].
AB  - Mast cells and eosinophils have been identified by differential stainings and
      counted in mucous membrane of nasal septum, turbinates and sinus of 77 ewes
      naturally infected with Oestrus ovis. Results have been compared with those of
      nine parasite free lambs. Anova tests indicate significant differences between
      infected and parasite-free sheep for the cell numbers and their distribution
      among the septum, the turbinates and the sinus and according to their position in
      mucous membrane, interglandular chorion of sub-mucosa. In infected sheep, the
      mean number of mast cells is twice the number present in parasite free animals.
      The burdens of eosinophils are multiplied by 17 for the septum, 29 for the
      turbinates and 58 for the sinus. The hypothesis of the development of an
      hypersensitivity phenomenon in ovine oestrosis is sustained by these results.

PMID- 9008736
TI  - Human cutaneous leishmaniasis: ultrastructural interactions between the
      inflammatory cells and Leishman bodies in the skin lesions.
AB  - The ultrastructural interactions between the inflammatory infiltrate and Leishman
      bodies (LBs) were described in skin lesions from 16 patients with acute cutaneous
      leishmaniasis. In early stages of the inflammation, the cellular infiltrate
      consisted of both undifferentiated and differentiated (activated) monocytes (M),
      macrophages (Mc), multinucleated giant cells (MNGC), plasma cells (PC),
      lymphocytes (Ly), and fibroblasts (F). In late stages, the infiltrate was in the
      form of tuberculous granulomas consisted mainly of type I secretory, and type II
      vesicular epithelioid cells (ECs), in addition to remnant of some inflammatory
      cells seen in the early stages. The two types of ECs were found only in six
      patients. The activated M, Mc and MNGC were often parasitized by LBs. The
      parasites were enclosed within the host cell digestive vacuoles (DVs), or
      phagolysosomes, together with skin melanosomes which are known to have lysosomal
      effect. In the DVs, LBs either survived or were killed and expelled from the host
      cell cytoplasm. This study showed, for the first time, that the melanosomes were
      apparently involved in killing of the LBs possibly by increasing the fatal
      effects of the DVs hydrolytic enzymes. Plasma cells were packed with large
      "Russell's bodies" indicating a high cellular immunoglobulin activity. The large,
      granular lymphocytes were in close contact to the activated M, possibly to
      promote delivery of activation signals. The type I secretory ECs contained mucin
      like granules with electrondense cores. In late stages of inflammation, the type
      II vesicular ECs contained lysosomal granules, and were found together with the
      type I ECs in broken-down tuberculous granulomas. The type I secretory ECs were
      previously thought to produce a mediator, or "granuloma factor" which recruits
      undifferentiated mononuclear cells to perpetuate the granulomatous process; while
      the type II vesicular ECs were thought to appear where the granulomatous process
      in brought to an end, preceeding the healing by fibrosis.

PMID- 9008737
TI  - [Evaluation of vectorial capacity of Glossina tachinoides (Diptera, Glossinidae)
      infected by Trypanosoma (Nannomonas) congolense: epidemiological implications].
AB  - A total of 182 Glossina tachinoides were infected with Trypanosoma congolense
      savannah type. Infection rates were determined according to microscopical
      examination of dissected flies and PCR on proboscis. Different techniques of
      trypanosomes detection in the saliva of live tsetse flies were compared. Results
      show a high percentage of immature infection rates. PCR amplification of
      trypanosomes in tsetse flies proboscis confirm parasitological observations. The
      salivation technique showed fluctuations of the number of trypanosomes deposited
      with saliva. Variability between individual flies was observed in the mean number
      of parasites ejected, the rate of positive salivates detected by PCR and the rate
      of infected mice. PCR technique was as efficient as parasitological technique to
      detect trypanosomes in the salivates. The infectivity on mice was the less
      efficient method. These results improve our knowledge on G. tachinoides vectorial
      competence in the laboratory, and precise the role of this tsetse species in the
      epidemiology of this disease.

PMID- 9008738
TI  - The expulsion of Echinostoma trivolvis: suppressive effects of dexamethasone on
      goblet cell hyperplasia and worm rejection in C3H/HeN mice.
AB  - C3H/HeN mice were infected with Echinostoma trivolvis metacercariae on day 0,
      given intramuscular injections of dexamethasone daily for 5 or 7 days, and
      necropsied on days 5, 8, 12, 15, 20 and 30 p. i. Controls consisted of mice that
      were infected with echinostomes, but were not treated with dexamethasone.
      Dexamethasone treatment caused a delay in worm expulsion from the small intestine
      of the hosts, and the increase in goblet cell numbers that occurred in untreated
      mice was markedly delayed in the treated mice. Mast cell number in the small
      intestine increased rapidly from just after day 5 p. i. and reached a peak on day
      15 p. i. in both dexamethasone-treated and control mice, although the increase in
      cell numbers was delayed slightly in the dexamethasone-treated mice. The
      eosinophil number in the small intestine of dexamethasone-treated mice was
      suppressed until 8 days p. i. and then increased reaching a peak on day 12 p. i.,
      although the number was about one half that of the control. As determined on day
      12 p. i., the mean body area of worms from dexamethasone-treated animals was
      significantly greater than that of the controls. Histological examination of the
      small intestine showed that the goblet and Paneth cell hyperplasia seen in mice
      infected with E. trivolvis was suppressed by dexamethasone treatment.
      Transmission electron microscopy revealed no marked ultrastructural differences
      in the small intestine of the dexamethasone-treated and control mice except that
      the former had an increased number of intracristal granules in mitochondria, an
      increase in vesicles in the apical epithelial cells and an increase in amorphous
      bodies and autophagic vacuoles in the Paneth cells. These results indicate that
      dexamethasone treatment delayed the expulsion of E. trivolvis from the small
      intestine of the host mouse in association with the suppression of goblet cell
      hyperplasia and increase in the number of mast cells and eosinophils.

PMID- 9008739
TI  - A quantitative approach to nematode lungworm burdens in goats.
AB  - Nematode lungworm burdens are difficult to evaluate of necropsy. The recovery of
      protostrongylid worms was achieved by three different post-mortem quantification
      techniques. Perfusion of the lungs under watertap pressure was successful in
      washing out Protostrongylus rufescens and Cystocaulus ocreatus but not Muellerius
      capillaris and Neostrongylus. Incubation of the lungs by pepsin and hydrochloric
      acid solution prior to perfusion helped to recover trapped Muellerius and
      Neostrongylus. Worm nodules were classified into type A, B and C, on increasing
      calcification process. Examination of these nodules showed that 75 to 80% of type
      A and B contained a parasite. Worms recovered by perfusion added to the sum of
      type A and B nodules were used to construct formula for quantifying the total
      lungworm burdens from naturally infected goat lungs and may provide a reasonable
      basis for assessing anthelmintic efficacy.

PMID- 9008740
TI  - [Autoimmunity: a concept generating explanatory tools].

PMID- 9008741
TI  - [Autoimmunity: a concept generating therapeutic tools].

PMID- 9008742
TI  - [Candida infections: new epidemiologic markers].

PMID- 9008743
TI  - [Amphotericin B deoxycholate (Fungizone): old drug, new versions].

PMID- 9008744
TI  - [Should patients with fibromyalgia be doped?].

PMID- 9008745
TI  - [Confusion syndromes in hospitalized aged patients: polymorphism of symptoms and
      course. Prospective study of 183 patients].
AB  - Using explicit criteria contained in the DSM III R, we collected in a prospective
      cohort study clinical features, outcome and risk factors from two cohorts of
      delirium in hospitalized elderly patients: 138 hospitalized in geriatric
      department and 45 patients admitted to an acute and comprehensive care hospital.
      The clinical features were assessed using a quantitative scale (developed by
      Derouesne). Delirium was unrecognized or misdiagnosed by physicians in 34% of the
      cases. The onset was known only two thirds of cases. The incidence of hyperactive
      type, prolonged hospital stay, poor outcomes (persistent delirium leading up to
      dementia) were highest in subjects admitted in comprehensive hospital. The
      etiology of delirium is complex and multifactorial. An underlying cause was
      identified in 80% of patients. The length or the worsening of delirium was
      significantly higher in patients with psychiatric or dementia comorbidity (OR:
      0.2; IC 95%: 0.1-0.5). The prognosis was better in patients without psychoactive
      medications (OR: 0.2; IC 95%: 0.1-0.4) or with metabolic abnormalities or acute
      diseases and disorders (OR: 3.3; IC 95%: 1.5-7.6). The predisposing factors to
      the development of dementia were prior use of psychoactive medications and signs
      of prior cognitive impairment. This article suggests delirium in elderly patients
      is associated with several outcomes. The prognosis should be improved at
      admission by specific scale and an evaluation of predisposing and precipitating
      factors.

PMID- 9008746
TI  - [Clinical manifestations of Chlamydia pneumoniae infections].
AB  - Chlamydia pneumoniae is a newly described and ubiquitous bacterium. Most
      infections are asymptomatic as shown by a high worldwide seroprevalence (> 50% of
      cases). It is a common cause of acute respiratory infections, mainly pneumonia (>
      50% of cases) and other acute respiratory tract infections (25% of acute
      bronchitis, < 5% of sinusitis, otitis and pharyngitis). About 10% of the
      community acquired pneumonia cases have been associated with Chlamydia pneumoniae
      infection. This incidence depends on a cyclic epidemiology with a high incidence
      for 2 to 3 years followed by a low prevalence for 3 to 4 years. Most chlamydial
      infections are mild but occasionally severe with death especially in old people.
      Mostly acute infections are recurrent infections. The seroprevalence is higher in
      asthmatic patients, its role in acute exacerbation of chronic bronchitis is not
      definitely established. Extra-respiratory acute infections are less frequent,
      either fever alone, or cardiovascular diseases (acute myocarditis, pericarditis
      and endocarditis) or neurological (encephalitis, meningitis or Guillain-Barre
      syndrome). In addition, seroepidemiology studies have shown an association with
      coronary artery disease, Chlamydia pneumoniae was detected in coronary atheroma
      by immunochemistry, polymerase chain reaction and by electron microscopy.
      Chlamydia pneumoniae may be involved in the atherosclerotic process. To define
      the clinical spectrum of infection requires precise laboratory diagnosis, the
      most efficient tests (PCR, direct immunofluorescence and culture) are done in
      specialized laboratories, serological tests are less reliable. Macrolides,
      cyclines and fluoroquinolones are the most potent antibiotics but with
      differences in vitro within and between these families of antibiotics.
      Bacteriological failures are described despite the in vitro activity. A lot of
      questions on clinical aspects, epidemiology and treatment are unanswered, we need
      more studies.

PMID- 9008747
TI  - [Malnutrition and HIV infection].
AB  - The wasting syndrome is well known in HIV infected patients. Predominant free
      fatty mass deletion is achieved. The weight loss results from decrease of food
      intake, from gut disorders due to HIV or opportunistic infections. Metabolic
      disorders are reported too. Breakdown of carbohydrates and proteins presents
      energy source. Raised free fatty acid turn over and hypertriglyceridemia are
      reported. Polyunsatured fatty acid level is raised inducing free radicals
      increase. Free radicals delete immune functions (apoptosis). Vitamin and trace
      element decrease worsen negative effects of free radicals.

PMID- 9008748
TI  - [Castleman's disease].
AB  - Castleman's disease, also called angiofollicular lymph node hyperplasia was first
      described as a distinct entity by Castleman et al in 1956. Two forms are now
      described a localized and a multicentric. The clinical and biological signs are
      varied and heterogeneous, and the diagnostic is made on the histologic
      examination. This atypical lymphoproliferative disorder is of unknown origin, but
      interleukin 6 play a central part in this disease. Despite the benignity of this
      "prelymphoma state", an aggressive course with poor prognosis occur usually in
      the multicentric form. Malignant lymphomas and Kaposi's sarcoma have been
      associated with Castleman's disease.

PMID- 9008749
TI  - [Oculopharyngeal myopathies: value of myotomy of the superior sphincter of the
      esophagus. Apropos of a case].
AB  - Since 3 years, a 74 year-old man suffered of swallowing impairment, weight loss,
      bilateral ptosis and proximal muscular weakness. Electron microscopy disclosed
      intranuclear tubular filaments and confirmed the diagnosis of oculopharyngeal
      muscular dystrophy. Upper oesophageal sphincter myotomy was performed with
      complete improvement. Four months after surgery, swallowing disorders were not
      recurrent and weight gain was substantial.

PMID- 9008750
TI  - [Familial porphyria cutanea tarda disclosed by chronic hepatitis C. Apropos of a
      case].
AB  - The hepatitis C virus (VHC) is probably the main aetiological factor of severe
      liver damages associated with the sporadic variety of porphyria cutanea tarda
      (PCT) in a 28 year-old woman revealed by a chronic C virus infection. Treatment
      with interferon alpha was delivered.

PMID- 9008751
TI  - [Merkel cell carcinoma: primary cutaneous neuroendocrine tumor].
AB  - Merkel cell carcinoma is a neuroendocrine primitive tumor of the skin. We report
      a case who develops node and visceral metastasis, and dead. The clinical
      presentation, diagnosis, histology, immunocytochemistry, treatment and prognosis
      of this tumor will be discussed.

PMID- 9008752
TI  - [Sweet's syndrome and aseptic abscess of the spleen].
AB  - Extra-cutaneous manifestations of neutrophilic dermatosis are exceptional and
      diverse: they consist of inflammatory infiltrates with neutrophil
      polymorphonuclears, without evidence of infectious agents. Localisations to the
      lung are the most frequently observed. A single observation of spleen involvement
      has been reported in a case of Sneddon-Wilkinson's disease. Herein we report the
      case of an aseptic splenic abscess during the course of a Sweet's syndrome.

PMID- 9008753
TI  - [Bone marrow aplasia related to ticlopidine].
AB  - The authors report two cases of bone marrow aplasia observed 2 months after
      initiation of a treatment with ticlopidine. The outcome was favorable after
      discontinuation of therapy. The frequency of this severe drug-induced
      complication seems to have been underestimated. The absolute necessity of a
      careful haematological survey during the first 3 months of therapy is pointed
      out.

PMID- 9008754
TI  - [False adrenal gland tumor].

PMID- 9008755
TI  - [Hypokalemic quadriparesis disclosing distal tubular acidosis in primary Gougerot
      Sjogren syndrome].

PMID- 9008756
TI  - [Ticlopidine (Ticlid) and severe bone marrow aplasia].

PMID- 9008757
TI  - [Horton disease, vascular pain of the face and sumatriptan].

PMID- 9008758
TI  - [Intra-alveolar hemorrhage of toxic origin and antineutrophil cytoplasmic
      antibodies (p-ANCA)].

PMID- 9008759
TI  - [Polynuclear neutrophils meningitis disclosing Mycoplasma pneumoniae infection].

PMID- 9008760
TI  - [Ischemic cerebrovascular complication disclosing primary antiphospholipid
      syndrome and an antithrombin III variant: a coagulation disorder].

PMID- 9008762
TI  - Iatrogenia in surgery: between incompetence and dishonesty.

PMID- 9008761
TI  - [Pneumococcal parotitis in human immunodeficiency virus infection].

PMID- 9008763
TI  - Iatrogenic injuries in surgery.

PMID- 9008764
TI  - The present status of surgery for lung cancer.
AB  - Surgical resection of non-small cell lung cancer (NSCLC) is the treatment of
      choice if complete resection is possible. There is consensus regarding a
      pretreatment minimal staging. For the pre-operative exploration CT scan (with
      contrast) and mediastinoscopy are complemental. Accepted is the New International
      Staging system with TNM. The 5-year survival following complete resection is
      stage-dependent. For stage I disease (T1-2, N0 M0) lobectomy is generally
      possible. The overall 5-year postoperative survival is 65%. No postoperative
      adjuvant treatment is necessary. For stage II (T1-2 N1 M0) lobectomy is possible
      in 70% of patients. The overall 5-year postoperative survival is 42.9%. Survival
      is affected by histology and T-status. The incidence of local recurrence can be
      reduced by postoperative radiotherapy. For stage III A (T1-3 N0-2 M0) surgery or
      combined modality treatment is indicated. The overall 5-year postoperative
      survival is 22.2%. For chest wall involvement (T3) en bloc resection of lung and
      partial chest wall is performed if possible. The 5-year survivors share common
      features: asymptomatic before operation, non-smokers, no rib erosion, squamous
      cell carcinoma, limited chest wall resection and N0 status. Pancoast tumours (T3)
      are treated according to the Paulson protocol with low dose pre-operative
      radiotherapy, complete en bloc resection, and postoperative radiotherapy in case
      of incomplete resection. Long-term survival after pre-operative irradiation and
      complete resection is possible. N1 or N2 disease is an adverse prognostic factor.
      When N2 disease is unsuspectedly discovered at operation, complete resection with
      mediastinal lymphadenectomy is indicated. The subgroup with the best prognosis is
      the group with negative mediastinoscopy, lobectomy and minimal N2. Multimodal
      therapy with chemo- or chemoradiotherapy is investigated. The results demonstrate
      the longest survival in patients with complete resection after major response to
      chemotherapy. For stage III B (T4 any N M0; any T N3 M0) surgery is usually not
      indicated and most patients are candidates for radio- or chemotherapy or both.
      The overall 5-year postoperative survival is 5.6% with 0% for N3 but 8.2% for T4
      patients, after extended resection as intrapericardial pneumonectomy, sleeve
      pneumonectomy, partial resection of the superior vena cava and miscellaneous
      partial resections. Postoperative radiotherapy may improve local control. For
      stage IV (any T any N M1) combined surgery can be effective for solitary adrenal
      or brain metastases. A reported 7.5% 5-year survival was mainly for
      intrapulmonary metastases, also considered as satellite nodules. Careful follow
      up of patients operated for lung cancer is necessary, as the incidence of
      metachronous lung cancer is as high as 10% for the long survivors. Reoperation
      with an economic but complete resection is the treatment of choice in the absence
      of metastases or other contraindications.

PMID- 9008765
TI  - Costing methodology in laparoscopic surgery.
AB  - This paper provides some basic insights in economic evaluation and costing
      methodology by means of illustrations in the field of laparoscopic surgery. Some
      general methodological aspects are discussed, as well as their impact on the
      calculation of both societal and hospital costs of medical interventions. First,
      Health Care Technology Assessment is described, and several techniques of
      economic evaluation in health care are situated in this area. Two fundamental
      concepts in costing analysis are discussed : opportunity costs and marginal (or
      incremental) analysis. Furthermore, it is argued that in designing an economic
      analysis, sufficient attention should be given to delineating the alternative
      treatment options and to determining the perspective from which the study is
      performed (patient, hospital, insurer, society,...). Subsequently, it is argued
      that all price and wage data for activities performed within a certain period
      should apply to the same time period. Finally, in order to facilitate overview,
      re-calculation and interpretation of cost data, it is advised to distinguish
      fixed from variable costs. Different categories of societal costs are described,
      as well as a number of methodologies for their evaluation. In calculating
      hospital costs, the costs of all different resources used (e.g. buildings,
      equipment, staff, materials) must be identified precisely. The issues of
      annuitising initial investment expenses, calculating operating and maintenance
      costs, and allocating labour and overhead costs are discussed. Finally, it is
      argued that, in all studies, it should be investigated whether the results of the
      economic analysis are robust to the models' assumptions, by means of sensitivity
      analysis. This paper provides a practical toolkit for medical doctors, to allow a
      correct understanding and critical analysis of economic literature in the field
      of laparoscopic surgery.

PMID- 9008766
TI  - Protection of intestinal anastomoses in septic environment with peritoneal graft
      and polyglycolic acid mesh: an experimental study.
AB  - We carried out an experimental study in dogs to evaluate the outcome of large
      bowel anastomosis with 6 stitches (Group C, n : 6) in a septic environment with
      protection by a polyglycolic acid (PGA) mesh (Group M, n : 12) or peritoneal
      graft (Group P, n : 12). Thirty dogs were used to compare the techniques. Two
      dogs in each group were re-operated after 3, 5, 7, 14, 28 and 90 days. They were
      evaluated for adhesion formation, lumen diameter (anastomotic index), clinical
      features, histologic appearance and quality of healing at the anastomotic sites.
      All dogs in group P and group M survived, whereas 2 dogs in the control group
      died of anastomotic leakage and 3 dogs were re-operated for anastomotic leakage
      and peritonitis. In group M, one dog was reoperated because of the anastomotic
      leakage and two dogs were reoperated because of the anastomotic stenosis. Also, 4
      anastomoses showed evidence of moderate stenosis. In group P, three anastomoses
      were graded as minimal stenosis. Histopathologic evaluation showed more complete
      epithelization, less inflammation, and less adhesion in group P than group M. We
      could not find any study in the literature that described and compared both
      techniques. We report here the results of such a study.

PMID- 9008767
TI  - Operative closure of patent ductus arteriosus in the neonatal intensive care
      unit.
AB  - Preterm infants undergoing surgical closure of patent ductus arteriosus are
      usually critically ill and are suffering from many concomitant diseases. The high
      risk of increased morbidity in transferring them from the neonatal intensive care
      unit (NICU) to a distant operating room is generally recognized. For this reason
      we report our experience in 33 premature infants with patent ductus arteriosus
      who have been operated in the NICU over a six-year period. There were no
      operative or immediate postoperative deaths and the 30 days hospital mortality
      was 6%. Based upon these findings we can confirm that operative closure of PDA
      can be performed safely in the NICU.

PMID- 9008768
TI  - The value of carotid stump pressure and EEG monitoring in predicting carotid
      cross-clamping intolerance.
AB  - The authors analyse their experience with carotid stump pressure (CSP) and
      electro-encephalogram (EEG) monitoring in relation to the incidence of
      peroperative stroke during internal carotid artery reconstruction. A series of
      215 patients is presented, among whom six (2.8%) developed a peroperative stroke.
      The stroke rate in patients with a CSP below 50 mm Hg (n = 92) was 7% (2/27)
      without a shunt and 3% (2/62) with the use of a shunt. The respective numbers for
      patients with a CSP equal to or above 50 mmHg were 1.7% (2/123) and 0% (0/10).
      The EEG remained normal after cross clamping in 180 cases (84%): the incidence of
      stroke was 1.5% (2/138) without and 5% (2/42) with a shunt. A shunt was used in
      33 of the 35 patients with EEG changes after cross clamping. None of them
      sustained a stroke in contrast to both patients where despite EEG changes no
      shunt was used (respective stroke rates 0% and 100%). It is concluded that
      regarding cerebral function, EEG monitoring provides more accurate information
      than CSP.

PMID- 9008769
TI  - Short-term survival after major pulmonary resections for bronchogenic carcinoma.
AB  - From January 27, 1992 to December 12, 1994, 100 consecutive patients (86 men and
      14 women) with a mean age of 62.5 years underwent lung resection for a non-small
      cell lung cancer. Squamous cell carcinoma was predominantly found (52%), followed
      by adenocarcinoma (23%) and large cell carcinoma (18%). Postoperative staging was
      Stage 0, 1 patient; Stage I, 57; Stage II, 17; Stage IIIa, 20 and Stage IIIb, 5.
      Thirty-day mortality was 4% (4 patients) with 10.7% for pneumonectomy and 0% for
      lobectomy or lesser resection. For the whole group 1-, 2- and 3-year survival
      rates were 83%, 68% and 65% respectively. Survival rates for N0, N1 and N2 after
      3 years were 70%, 59% and 54% respectively. In the univariate analysis, a trend
      to statistical significance was noted between N0 and N1 (p = 0.08). There was no
      difference in short-term survival between N0 and N2 which represents a highly
      selected group of patients with N2 disease. In the multivariate analysis the only
      two independent variables with impact on survival were number of pack-years and
      diameter of the tumour (p < 0.05). Ninety-two quality of life questionnaires
      (EORTC QLQ-C30) were sent to home physicians. We collected 31 questionnaires
      (34%) after 2.5 months. A clear relationship was not seen between complaints of
      pain or dyspnea and extent of resection or lung function postoperatively.
      Instead, the global quality of life seemed to be influenced by the extent of
      resection to the advantage of a lobectomy and disadvantage of a pneumonectomy.
      Difficulties related to quality of life analysis are discussed and future
      directions are given.

PMID- 9008770
TI  - Paraoesophageal hernia with acute intrathoracic volvulus of the stomach after
      laparoscopic Nissen fundoplication.
AB  - In experienced hands, the value of the laparoscopic Nissen fundoplication as
      antireflux correction is established. The case report concerns a woman who
      underwent an emergency laparotomy for acute intrathoracic stomach volvulus with
      incarceration, one year after a laparoscopic Nissen fundoplication was carried
      out without closure of the diaphragmatic hiatus. In literature acute
      postoperative paraoesophageal hernia with intrathoracic migration of the stomach
      as an early and late complication of the laparoscopic fundoplication has already
      been reported. The authors advocate the closure of the diaphragmatic crura as a
      routine manoeuvre during the laparoscopic fundoplication.

PMID- 9008771
TI  - Adult intussusception. A case report.
AB  - The intussusception in adults is very rare. Symptoms are atypic and diagnosis is
      difficult. We present the case of an 85-year-old female admitted for vague
      intermittent diffuse abdominal pain since 3 months, with episode of diarrhoea. A
      mobile mass was palpable in the right iliac fossa. The barium transit
      demonstrated a filiform stenosis of the last segment of ileum in the caecum.
      Scanner showed a "target mass". An ileal intussusception on caecal tumour was
      suggested and confirmed by laparotomy. This entity is confronted with the
      literature reports. The aetiology, clinical presentation, diagnosis and treatment
      are discussed.

PMID- 9008772
TI  - Intussusception of vermiform appendix. A case report and review of the
      literature.
AB  - Intussusception of the appendix into the caecum is an uncommon condition and the
      diagnosis is rarely made preoperatively. Specific anatomic requirements as well
      as pathological conditions causing irritation or increasing peristalsis should be
      present for this event to occur. A case is discussed in which the diagnosis was
      made of an ileocolic invagination, which appeared peroperatively to be an
      appendicular invagination.

PMID- 9008773
TI  - Traumatic rupture of the thoracic aorta: the diagnostic challenge.
AB  - The traumatic rupture of the thoracic aorta is a severe and lifethreatening
      entity. It is therefore important to diagnose this lesion. Classically, this is
      based on the detection of a widened superior mediastinum on chest X-ray. However,
      several factors like supine position, obesity, mediastinal haematoma,... might
      bias the diagnosis. The authors present four different clinical presentations of
      traumatic rupture of the thoracic aorta and describe how the lesion was detected.
      Subsequently, they review the literature on the diagnostic approach of this
      severe lesion.

PMID- 9008774
TI  - Primary actinomycosis of the urinary bladder. Case report and review of the
      literature.
AB  - The case of a female patient, aged 37, with signs of partial intestinal
      obstruction, repeated cystitis and a tumoral mass in the hypogastrium is
      reported. Preoperative examinations could not establish the nature of the tumour.
      Colonoscopy as well as barium enema stopped at a sharp angulation of the sigmoid.
      Laparotomy evidenced an inflammatory tumour, with departure point in the urinary
      bladder, which involved the sigmoid and the uterus. After adhesiotomy a partial
      cystectomy was performed. The macroscopic aspect of the bladder was
      pseudopolypoid, while the microscopic one was typical for actinomycosis. The
      patient was discharged cured and was prescribed a penicillin course for 4 weeks.

PMID- 9008775
TI  - Chronic intrathecal baclofen in severely disabling spasticity.

PMID- 9008776
TI  - Piracetam in the treatment of myoclonus: an overview.
AB  - Myoclonus is a rare, but disabling symptom, occurring in a number of diseases of
      different origin. Aetiological and neurophysiological classifications, as well as
      the current treatment in myoclonus are discussed. An overview of the treatment of
      myoclonus with piracetam in 62 case reports, 3 open trials and 2 doubleblind
      trials, covering 171 patients is reported.

PMID- 9008777
TI  - Lithium neurotoxicity at low therapeutic doses Hypotheses for causes and
      mechanism of action following a retrospective analysis of published case reports.
AB  - Lithium has been the pharmacologic treatment for the management of manic
      depressive illness for many years. While the therapeutic efficacy of lithium is
      invaluable, it can cause a variety of neurotoxicities at normal therapeutic doses
      or concentrations. A systematic search through the Medline database was
      performed. 41 Cases of neurotoxic adverse effects of lithium at low therapeutic
      concentrations were observed (< 65 years, 14 males & 21 females/> 65 years, 6
      females). Although a higher percentage of female subjects experienced lithium
      neurotoxicity, no statistically significant difference between the two groups was
      noted (Fisher's exact test, P = 0.07). The analysis of the data shows that among
      case reports of lithium neurotoxicity, drug interaction effect is an important
      factor. More than 50% (51.2%) of the patients received at least one neuroleptic
      medication with their lithium treatment, 22% received concomitantly an
      antidepressant, 22% an antiepileptic (carbamazepine) and 17% an anxiolytic. It is
      our hypothesis that these drug associations are an important contributing factor
      to lithium neurotoxicity. The high percentage of neurotoxicity which is
      associated with neuroleptics warrant caution in the daily clinical practice when
      these two classes of medications are combined. It is hypothesised that
      neuroleptics, in particular the phenothiazines, might increase lithium influx in
      red blood cells and that the enhanced levels of lithium in the tissue may
      possibly be responsible for the neurotoxic effects. Concomitant administration of
      medications such as neuroleptics with lithium require caution with regular
      clinical observations and drug plasma concentration monitoring.

PMID- 9008778
TI  - Gliomatosis cerebri: clinical, radiological and pathological report of a case
      with a stroke-like onset.
AB  - A 62 year-old man was admitted with a right hemiparesis, sensory aphasia and
      right hemianopia which appeared on awakening. He was initially thought to have a
      stroke, but EEG showed diffuse slowing and both CT scan and MRI irregular white
      matter lesion suggesting a leucoencephalopathy. His neurological deficit
      regressed, and he was discharged after 2 weeks. He was readmitted 6 months later
      because of mental confusion. MRI revealed diffuse white matter lesions extending
      up to the frontal lobes, these were hyperintense on T2 weighted images and
      suggested the diagnosis of gliomatosis cerebri (GC). The patient became
      progressively comatose and died 6 weeks later. At autopsy the brain looked
      diffusely swollen with irregular greyish areas of the white matter of both
      centrum ovale and brain stem. On microscopic examination the cerebrum and brain
      stem were diffusely and asymmetrically infiltrated by numerous neoplastic glial
      cells without angiogenesis or disruption of architectonic boundaries. There were
      no mitoses nor necrosis. Many tumour cells were GFAP- and S100-positive. A high
      proportion of cells contained the leucocyte antigen Leu-7. This case of
      gliomatosis cerebri is compared to the 9 published cases of GC with an initial
      focal neurological deficit and to the 19 publications reporting MRI results. The
      controversial nosological boundaries and etiopathogenetic hypotheses of this
      peculiar neoplastic disease are discussed.

PMID- 9008779
TI  - Thyrotoxic periodic paralysis, an unusual cause of hypokalemic periodic
      paralysis.
AB  - Over a two-year period two patients were admitted to the hospital with episodes
      of paralysis and hypokalemia. In the first patient, familial hypokalemic periodic
      paralysis was initially suspected. Only several months later was Graves' disease
      diagnosed and this diagnosis linked to thyrotoxic periodic paralysis. The second
      patient came to notice after treatment with thyreostatic drugs was stopped
      prematurely and paralysis together with hypokalemia developed. Thyrotoxic
      periodic paralysis, being rare outside Asia, closely mimics the clinical
      presentation of familial hypokalemic periodic paralysis. Mainly men in the third
      decade with a negative family history are affected. Graves' disease is the most
      common cause of hyperthyroidism. This disorder is not always clinically apparent
      since signs of hyperthyroidism may be easily missed. Therefore thyroid function
      tests are part of the diagnostic workup of hypokalemic periodic paralysis.
      Correction of thyroid function is essential to treatment. The pathophysiology is
      still controversial.

PMID- 9008781
TI  - Multiple calcified brain metastases revealing a lung carcinoma.
AB  - The case of a 50-year-old man with multiple calcified brain metastases revealing
      an undifferentiated lung carcinoma after a delay of two months, is reported. A
      slow and progressive clinical evolution was noted. Eight months after the brain
      lesion had been discovered, intramedullary and epidural spinal metastases
      appeared. However, the calcified brain metastases remained stable 11 months after
      the diagnosis. One month later the patient died after several episodes of
      generalized seizures.

PMID- 9008780
TI  - Delayed-onset hemidystonia and chorea following contralateral infarction of the
      posterolateral thalamus. A case report.
AB  - A 68 year-old man developed progressive hemidystonia and chorea 8 months after a
      contralateral thalamic stroke. The neurological examination also showed a right
      pyramidal syndrome without hemiparesis, a right horizontal sectoranopia, and a
      right hemihypesthesia for all sensory modalities. The MRI revealed infarctions in
      the left medial temporo-occipital lobes and left posterolateral thalamus,
      corresponding to the vascular territories of both the thalamo-geniculate and
      posterolateral choroidal arterial pedicles. The thalamic lesion involved the
      pulvinar, the lateral geniculate body, and the ventro-postero-lateral, dorso
      lateral, posterolateral, and dorso-medial nuclei, but apparently did not extent
      to the ventrolateral thalamic nucleus, and the subthalamic and midbrain regions.
      Thalamic and striatopallidal dystonia have not a common pathophysiological
      mechanism. The involvement of the pulvinar nucleus and of the strategic crossing
      of proprioceptive, cerebellar, pyramidal, and subthalamic pathways may play a
      role in the genesis of the posterolateral thalamic dystonia.

PMID- 9008782
TI  - Cerebellar ataxia in upper limbs triggered by addition of carbamazepine to
      lithium treatment.

PMID- 9008783
TI  - The role of cerebrovascular ultrasonography in acute stroke.

PMID- 9008784
TI  - The role of echocardiography in the evaluation of patients with ischemic stroke.

PMID- 9008785
TI  - MR imaging of a metastasis in a meningioma.
AB  - We describe the MRI findings in a case of metastasis of a parotid adenocarcinoma
      into an intracranial meningioma. The lateral part of the tumour had atypical
      signal characteristics, suggesting the presence of another tumour in the
      meningioma.

PMID- 9008787
TI  - Detection of a new variant phenotype of phosphohexose isomerase in the Gadaba
      tribe of Andhra Pradesh, south India.
AB  - A total of 998 unrelated individuals from the Gadaba tribal population of Andhra
      Pradesh, South India, were screened for red cell phosphohexose isomerase (PHI) by
      starch gel electrophoresis. A new and hitherto for Andhra Pradesh not yet
      reported rare variant phenotype was observed: PHI 6-1. The new allele is
      designated as PHI*6Gadaba.

PMID- 9008786
TI  - Bilateral asymmetry in dental discrete traits in human isolates: south Sinai
      Bedouin tribes.
AB  - Data are presented on dental morphology as adjudged from dental casts of children
      (boys and girls) 6-13 years of age from four Bedouin tribes of Southern Sinai
      (Gebeliya, Muzeina, Hamada and Aliquat) and a mixed group designated as "other
      tribes", (Awlad Said, Gararsha, Sawalcha, Haweitat and Beni-Wassal). Alginate was
      the impression material used and the casts were made of artificial stone poured
      into the irreversible hydrocolloid impression. A total of 352 casts were
      available for study. In the maxilla, 29 dental discrete traits of permanent teeth
      and 2 traits of deciduous teeth were observed, and in the mandible, 24 traits of
      permanent teeth and 2 traits of deciduous teeth; in all, 57 traits were observed.
      Only clear traits were considered. From the studied 57 traits only 30
      morphological traits were used for the estimation of the asymmetry. Total
      symmetry was observed in 2 mandibular teeth and traits: a) Lateral incisor-LI
      slight inclination; b) Canine-Cn-no lingual cingulum and in 3 maxillary teeth and
      traits a) Central incisor-CI-slight convexity of labial profile curvature; b)
      First premolar-PM1-intercuspal distance more than 3 mm; and c) Second molar,-M2
      pit groove pattern similar to the first molar. Low values of asymmetry (1-5.1%)
      were observed in traits describing outline form and shape, surface outline, and
      number of cusps in three maxillary and two mandibular teeth (nine discrete
      traits). High values of asymmetry (12.7-37.0%) were observed regarding traits
      describing styles on slopes, ridges, pits, grooves and lingual tubercles in three
      maxillary and one mandibular teeth (15 discrete traits). The high rate in molars
      was higher than that in the incisors. A higher rate of asymmetry occurred in the
      maxilla than in the mandible.

PMID- 9008788
TI  - Distribution of hair on the dorsum of the phalanges of the hand in a Chinese
      population from Malaysia.
AB  - Hair distribution on the dorsum of phalanges of the hand was studied on 302
      Chinese subjects (134 males and 168 females) randomly selected from the residents
      of Kota Bharu, Malaysia. Proximal phalangeal hair was seen on the dorsum of both
      hands in 99.3% of male subjects but in only 85.1% of female subjects. Chinese
      females showed a significantly lower (p < 0.05) incidence of proximal phalangeal
      hair on the hands than Chinese males. Comparison with other racial groups showed
      that Chinese females had significantly less (p < 0.05) hair on the proximal
      phalanges of the hands than Malay and African (Nigerian) females. The least
      common digital combination of proximal phalangeal hair in female subjects was the
      presence of proximal phalangeal hair only on the fourth digit (ring finger) and
      was noted in 0.6% of subjects. This has not been reported before. The frequency
      of middle phalangeal hair (MPH) distribution in Chinese falls between that in
      Malays and in Japanese which is probably explained by the fact that all these
      three racial groups originate from Asia. A study of digital combination of MPH in
      Chinese showed that the most common and the least common combinations in the
      Chinese differ considerably from those in other races. A total of 16 patterns of
      hair distribution was noted on the dorsum of the phalanges of the hands in
      Chinese subjects. Our study showed that though Chinese females had less digital
      hair on the hands than Chinese males, they showed a much larger variety of
      patterns of digital hair distribution than males.

PMID- 9008789
TI  - Study of the matrimonial structure of the population of central Sardinia (Italy).
AB  - Temporal changes in the matrimonial structure of four Sardinian populations
      (Bitti, Lula, Lode and Gavoi) have been studied. The endogamy rates and the
      average marriage distances indicate that the four villages experienced a long
      period of isolation. Only in recent decades endogamous marriages have fallen
      shortly. The trends of marital isonymy and inbreeding, evaluated both from
      isonymy and dispensation for consanguineous marriages, are similar to those of
      endogamy. The kinship values between pairs of populations show some preferential
      relationship (Bitti-Lode, Lode-Lula) and an evident differentiation between Gavoi
      and Bitti. The results also indicate that the values of kinship are not
      associated with the geographic distances. The possible impact of the matrimonial
      structure on the genetic structure and the relationships among the studied
      populations will be examined in further investigations, in which the genetic
      markers will be considered.

PMID- 9008790
TI  - Electrophoretic analysis of mammalian hair keratins.
AB  - Keratins extracted from the hair of several mammals were characterized by sodium
      dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric
      focusing (IEF). By SDS-PAGE, most differences between species were detected in
      the position and intensity of polypeptide bands with MW in the range 30-10 KDa
      (high sulphur keratins, hair matrix proteins, HMP). By IEF, differences were
      found in the intensity of polypeptide bands in the acidic pH range (< 5.1).
      Electrophoretic techniques could therefore have a taxonomic usefulness.

PMID- 9008791
TI  - Gender difference in cereal intake: possible impacts of social group affiliation
      and season.
AB  - Food may not be equitably distributed within the household. The distribution
      depends on some factors, one of which is availability of food. The generalised
      proposition of gender bias against women in the distribution of food in South
      Asia has been examined here in three culturally contrasting population groups in
      two seasons, viz. lean and peak. The result shows that in all the three groups,
      in all household membership categories, the intake of cereal is higher than the
      recommended intake, but the male-female differences in net intakes are higher in
      peak season than in lean season.

PMID- 9008792
TI  - Blood pressure and its correlates in the population of Multan, Pakistan.
AB  - In a randomly selected sample of 1579 individuals (male = 1334 and female = 245),
      aging from 14 to 65 years and representing all the socioeconomic groups of
      Multan, age (Yr), height (cm), weight (kg), BMI (kg/ml) and blood pressure (mmHg)
      were recorded. Height was measured on a Holtain portable stadiometer, weight on
      beam scale and blood pressure was recorded with sphygmomanometer as per
      auscultatory method. The correlation coefficient between different independent
      (age, height, weight and BMI) and dependent (SBP, DBP and MAP) parameters in
      male, female and total population were calculated and strong association between
      different parameters was observed (p < 0.001 or p < 0.05). The regression
      equations (simple and multiple) were worked out. The regression coefficient of
      different independent parameters with dependent parameters are higher in female
      except for height and age-weight and age-BMI had higher contribution in female as
      compared with that of male.

PMID- 9008793
TI  - Detection of antibodies against Actinobacillus pleuropneumoniae serotype 5 using
      an inhibition enzyme immunoassay.
AB  - An inhibition enzyme immunoassay (EIA) for detection of antibodies against A.
      pleuropneumoniae serotype 5 (App-5) in pig sera, based on the inhibition of the
      binding of an App-5 specific monoclonal antibody was established. The monoclonal
      antibody (MAb 210-F11) was found to be directed against an epitope on the O-chain
      of App-5 LPS. In the inhibition EIA, highly purified App-5 LPS was used to coat
      microtitre plates. Serial dilutions of pig sera were added to the plates prior to
      the addition of the MAb 210-F11. The degree of binding of App-5 antibodies from
      pig sera was determined as the percentage inhibition of the MAb 210-F11. Pig
      serum from specific pathogen free (SPF) herds, from experimentally infected
      animals, and from acutely and chronically infected herds were tested. A serum
      dilution of 1/30 was found to be optimal, when using 50% inhibition as the
      discriminating inhibition percentage. No cross-reactivity was observed with serum
      from pigs infected with other App serotypes or bacteria isolated from the
      respiratory tract, such as A. suis and H. parasuis. The inhibition EIA will be
      used for surveillance of App-5 antibodies in SPF and conventional herds.

PMID- 9008794
TI  - Competitive and indirect enzyme-linked immunosorbent assays for Mycobacterium
      bovis infections based on MPB70 and lipoarabinomannan antigens.
AB  - A competitive enzyme-linked immunosorbent assay (C-ELISA) using M. bovis BCG
      Tokyo culture filtrate as antigen and anti-MPB70 4C3/17 monoclonal antibody was
      developed for use in multiple animal species. An analysis of the C-ELISA data for
      cattle and bison serum panels revealed specificities of 68% to 85% and
      sensitivities of 85% to 89%. Receiver operator characteristics (ROC) of this data
      revealed areas of 81% to 92% for C-ELISA and demonstrated that C-ELISA as well as
      the indirect ELISA protocols, MPB70-ELISA and LAM-ELISA, discriminate M. bovis
      infected animals from non-infected animals for these particular panels. The kappa
      statistic values for agreement beyond chance between C-ELISA and MPB70-ELISA were
      determined after ELISA cutoffs were adjusted to minimize false positives. There
      were poor to excellent agreements between C-ELISA and MPB70-ELISA in all species
      tested (Bovidae, Cervidae, and Camelidae) that were consistently higher than the
      kappa statistic between C-ELISA and LAM-ELISA. The humoral response to one
      antigen and little or no response to the other in many animals argued for a
      parallel interpretation of C-ELISA and LAM-ELISA to increase sensitivity.

PMID- 9008795
TI  - A polymerase chain reaction assay for the detection of Leptospira spp. in bovine
      semen.
AB  - A rapid and specific method for the detection of pathogenic Leptospira spp. in
      bovine semen using the polymerase chain reaction (PCR) is described. The primers
      used were derived from an EcoR1/BamH1 fragment that hybridized strongly to
      chromosomal DNA from the hardjobovis serovar. Three different extraction methods
      were evaluated in this study: phenol-chloroform extraction method, proteinase K
      (PK) in 1% SDS, followed by phenol-chloroform, and phenol-chloroform followed by
      1% cetyltrimethylammonium bromide (CTAB). A PCR product of approximately 500 base
      pairs (bp) in length was obtained when DNA from pure Leptospira culture was used
      as a template for PCR, regardless of the DNA extraction method used. The product
      was consistent with that predicted from the gene sequence. However, in semen
      seeded in vitro, as well as in semen from infected bulls, a PCR product was
      obtained only when the leptospiral DNA was extracted from the specimen using the
      CTAB method. In contrast, other methods used for DNA extraction did not generate
      suitable templates for the PCR procedure. This is the first PCR protocol
      developed to detect Leptospira in bovine semen. The PCR protocol provided a
      direct and unequivocal demonstration that Leptospira can be detected in semen of
      infected animals. The CTAB method was also used successfully in detecting
      Leptospira in the urine of infected animals. The PCR procedure was shown to be
      more sensitive than either the fluorescent antibody test (FAT) or culture for
      detecting the organism in urine.

PMID- 9008796
TI  - Morphometry of the small intestine in pigs with ileo-rectal anastomosis.
AB  - Ileo-rectal anastomosis (IRA), which is frequently used to measure prececal
      digestibility in pigs, could induce some disturbances of the normal absorptive
      function. Our aim was to investigate the effects of different IRA surgical
      procedures on the main histologic characteristics of the small intestine in pigs.
      The 4 different IRA procedures compared to intact pigs (INT) were the following:
      either end to end (EE) or end to side (ES) with or without preservation of the
      ileocecal valve (EEV, EE, ESV, ES respectively). At 147 d after surgery, samples
      of the wall of the duodenum, jejunum and ileum were taken under anesthesia and
      histometric examinations were performed on HE- and PAS-colored sections to
      estimate changes mainly of mucosa and muscle layers. The values recorded for
      villus length, crypt depth, and whole thickness of the mucosa suggested that the
      EE procedures disturb the small intestine less than the ES models. A new
      parameter, called epithelial quotient and calculated as [(villus length/crypt
      depth)/mitotic index], was proposed to improve the comparisons. According to this
      quotient, EE procedures did not significantly affect the mucosa of the whole
      small intestine. An increased density of goblet cells was recorded in all
      operated pigs along the small intestine, but mainly in the ileum after EE-IRA.
      The lymphatic follicle area was reduced. These findings, which were in agreement
      with a reduced mitotic index in the ileum of EE-pigs, indicated a decreased
      effect of noxious factors on the small intestinal mucosa in IRA-pigs, especially
      after the EE-IRA procedure. Some atrophic or hypertrophic effects on the muscle
      layers were related to the absence or preservation of the ileo-cecal valve.
      Finally it was concluded that i) there was no major disturbance after IRA, and
      ii) the end to end procedure was most beneficial for the structural integrity of
      the small intestine.

PMID- 9008798
TI  - Antigenic variation among bovine viral diarrhea virus (BVDV) strains and the role
      of different cell fixation methods in immunoassays.
AB  - Antigenic variation among 13 Quebec isolates of bovine viral diarrhea virus
      (BVDV), 4 reference strains and 2 American isolates were studied by peroxidase
      linked antibody assay (PLA assay) and neutralization test (NT). The Quebec
      strains consisted of 3 isolates before 1993 and 10 isolates from 1993. In the PLA
      assay, we compared 2 different fixatives, acetone and formalin. Acetone-fixation
      allowed us to identify 6 groups from amongst the viruses tested. All the Quebec
      isolates were different from the reference strains. In addition, antigenic
      variation was detected between Quebec isolates obtained before and during 1993.
      However, PLA assays performed after formalin fixation did not detect these
      antigenic variations. Neutralization tests were carried out with 2 polyclonal
      antibodies (PAb) and 6 monoclonal antibodies (MAb). They were used to classify
      BVDV strains and isolates into 4 groups and 7 subgroups respectively. In
      conclusion, we demonstrated that the BVDV isolates from the 1993 outbreak in
      Quebec are antigenically different from reference strains and from isolates
      existing in Quebec before 1993. In addition, we have shown that 2 internationally
      used fixation-methods in PLA assay give different results. The usefulness of each
      method is discussed.

PMID- 9008797
TI  - Functional analysis of antibody responses of feedlot cattle to bovine respiratory
      syncytial virus following vaccination with mixed vaccines.
AB  - The antibody response of cattle to bovine respiratory syncytial virus (BRSV)
      immunization was investigated using 4 different commercially available mixed
      vaccines. Forty, 5-6 month old, beef calves, randomly assigned to groups of 10,
      were vaccinated on day 0 and 21 with 1 of 3 inactivated vaccines, (3 groups), or
      a modified live virus (MLV) vaccine. BRSV-specific antibody responses were
      measured prior to vaccination and on day 35 by using an enzyme linked
      immunosorbent assay (ELISA), virus neutralization assay (VN), a fusion inhibition
      assay (FI); and responses were also measured for their ability to facilitate
      antibody dependent, complement mediated cytotoxicity (ADCMC) of BRSV infected
      cells. Sera from day 35 were, in addition, analyzed by use of an IgG1, IgG2
      isotype specific ELISA. All vaccines induced significant increases in BRSV
      specific IgG antibody as measured by ELISA, but only one inactivated and the MLV
      vaccine induced significant increases in VN titers. Fusion inhibiting antibody
      titers were low or undetected in calves vaccinated with the inactivated vaccines.
      Vaccination with modified live virus induced significantly higher titers of
      fusion inhibiting antibodies, which are considered to be most highly correlated
      with protection. The VN to ELISA and FI to ELISA ratio of the calves that
      received MLV vaccine were significantly greater than the calves receiving the 3
      inactivated vaccines. Vaccination with MLV induced the highest IgG2/IgG1 ratio.
      This difference was small, and only significant relative to 2 of the inactivated
      vaccine groups, which were not significantly different from each other. The
      higher proportion of IgG2 isotype in the MLV sera was not associated with lower
      ADCMC, a function not attributed to this isotype. The VN and FI titers, but not
      the ELISA value of the sera, were most predictive of ADCMC. The inactivation
      processes apparently alter epitopes and affect the induction of functional
      antibodies.

PMID- 9008799
TI  - Duration of immunity in foxes vaccinated orally with ERA vaccine in a bait.
AB  - Red foxes (Vulpes vulpes) vaccinated orally with the ERA strain of rabies vaccine
      in a bait were challenged after 83 mo. Ten of 11 foxes that had seroconverted
      following vaccination resisted challenge with a virulent rabies virus which
      produced clinical signs of rabies in 6 of 6 unvaccinated foxes. Five of 11
      vaccinated animals retained titers of rabies virus neutralizing antibody
      throughout the period. Although 6 of 11 had no detectable antibody at the time of
      challenge, 5 of these 6 resisted challenge and had an anamnestic response, as
      indicated by elevated titers of antibody when measured at day 77 postchallenge.
      These results show that foxes can be immunized successfully with a single oral
      dose of ERA vaccine, probably with protection against a lethal rabies challenge,
      for at least 7 y.

PMID- 9008800
TI  - Effect of glutamine or glycine containing oral electrolyte solutions on mucosal
      morphology, clinical and biochemical findings, in calves with viral induced
      diarrhea.
AB  - Twenty-one diarrheic calves were randomly assigned to 1 of 3 oral electrolyte
      treatments. The treatments were either a conventional oral electrolyte containing
      glycine (40 mmol/L) as the amino acid, an oral electrolyte in which glutamine (40
      mmol/L) replaced glycine or an electrolyte in which high concentrations of
      glutamine (400 mmol/L) replaced glycine. The calves were monitored while on trial
      and at the end of the treatment they were euthanized and a necropsy was
      immediately performed. Calves fed the high glutamine electrolyte had more
      treatment failures (2/7 versus 0/7 for each of the other 2 treatments). There was
      a significant effect of type of electrolyte on fecal consistency. Calves fed the
      glycine containing electrolyte had the most solid feces. Duodenal villus height
      was significantly affected by the type of electrolyte: values (mean +/- 1 SEM)
      were 0.61 +/- 0.09, 0.46 +/- 0.05, and 0.59 +/- 0.07 mm for high glutamine, low
      glutamine and glycine electrolytes respectively. There was no significant
      difference in small intestinal surface area between groups. High glutamine
      treated calves had the greatest capacity to absorb xylose from the small
      intestine but this difference was not statistically significant. Overall, this
      trial does not suggest that substituting glutamine for glycine in oral
      electrolyte solutions improves treatment of diarrheic calves or speeds mucosal
      healing.

PMID- 9008801
TI  - Mycotoxins in fungal contaminated samples of animal feed from western Canada,
      1982-1994.
AB  - Feed samples from 94 cases involving fungal contamination and suspected
      mycotoxicosis of farm animals in western Canada were examined during 1982-1994 to
      assess the incidence of mycotoxins. Samples were analyzed for aflatoxins,
      ochratoxin A, citrinin, sterigmatocystin, and the fungal estrogen zearalenone.
      Samples infected with Fusarium fungi were additionally assayed for nivalenol,
      deoxynivalenol, fusarenone-x, 15-acetyl-deoxynivalenol, diacetoxyscirpenol, HT-2
      toxin, and T-2 toxin. Mycotoxins were found in 21 feed samples from 17 cases (18%
      of the reported cases), generally at levels far below those needed to induce
      symptoms under laboratory conditions. HT-2 toxin and other type-A trichothecenes
      were detected in 5 samples, deoxynivalenol and other type-B trichothecenes in 13,
      ochratoxin A in 5, and citrinin in 2. In 9 cases, symptoms observed in the
      animals were consistent with the known effects of the mycotoxin(s) found in the
      particular feed samples.

PMID- 9008802
TI  - Investigation of the effects of hyperthyroidism on renal function in the cat.
AB  - This study evaluated the effects of thyroxine on renal function in the cat.
      Baseline serum thyroxine (T4) concentrations, clinicopathologic data (complete
      blood count [CBC], serum chemistry panel, urinalysis), and nuclear medicine
      determinations of glomerular filtration rate (GFR), effective renal plasma flow
      (ERPF), and effective renal blood flow (ERBF) were measured in 10 normal adult
      cats. Cats were then injected with thyroxine (T4) (50 micrograms/kg SQ) daily for
      30 d to induce hyperthyroidism. Clinicopathologic and nuclear medicine studies
      were repeated at 30 d. Cats injected with thyroxine had significant increases in
      T4, GFR, and ERBF and significant declines in serum creatinine and blood urea
      nitrogen (BUN) values. Administration of high doses of exogenous thyroxine to
      cats results in significant stimulation of renal function.

PMID- 9008803
TI  - Relationship between the chemiluminescent response of bovine neutrophils and
      changes in intracellular free calcium concentration.
AB  - The relationship between luminol dependent chemiluminescent (LDCL) response and
      changes in intracellular free Ca2+ concentrations in the bovine neutrophils was
      evaluated. LDCL responses and changes in intracellular Ca2+ concentrations of
      neutrophils were clearly detected by the stimulation with opsonized zymosan
      (OPZ), concanavalin A(ConA), heat-aggregated IgG (H-agg.IgG) and phorbol
      myristate acetate (PMA). Patterns of LDCL responses and intracellular Ca2+ of
      neutrophils showed characteristic features for each stimulant. PMA was a weak
      stimulant of the intracellular Ca2+ concentration, whereas it was a strong
      stimulant of LDCL response. Con A strongly stimulated an increase in the
      intracellular Ca2+ concentration, but was a weak stimulant of LDCL response. LDCL
      response of intracellular Ca(2+)-depleted neutrophils treated with ionomycin,
      stimulated with each stimulant was inhibited markedly without extracellular Ca2+.
      The sustained phase of intracellular Ca2+ concentrations stimulated with OPZ was
      inhibited significantly (P < 0.05) by the preincubation with anti-CD18 antibody,
      whereas the transient phase of intracellular Ca2+ concentrations was not
      inhibited. These results indicate that LDCL response is regulated at least in
      part by the elevation of the intracellular Ca2+, and a rise in intracellular Ca2+
      concentration, which may be mediated by specific receptors appears to be
      essential in the LDCL response of bovine neutrophils.

PMID- 9008804
TI  - Serodiagnosis of swine pleuropneumonia due to Actinobacillus pleuropneumoniae
      serotypes 7 and 4 using long-chain lipopolysaccharides.
AB  - A saline boiled extract (SBE), capsular polysaccharides (CPS) and long-chain
      lipopolysaccharides (LC-LPS) of Actinobacillus pleuropneumoniae serotype 7 have
      been evaluated in ELISA for the serodiagnosis of swine pleuropneumonia caused by
      this serotype. Mean optical densities (ODs) obtained with the 3 antigens using
      sera from negative herds as well as from animals experimentally and naturally
      exposed to A. pleuropneumoniae serotypes 7 or 4 were not statistically different.
      The positive ELISA reaction with anti-serotype 4 sera was unexpected with the
      CPS, which are supposed to be serotype-specific; LPS traces present in the CPS
      appeared to be responsible for this reaction. In addition, sera from animals
      exposed to A. pleuropneumoniae serotypes 5 or 10 presented cross-reactions with
      the SBE and the CPS, but not with the LC-LPS. Cross-reactions were mainly due to
      rough LPS, as shown by immunoblotting. The LC-LPS is easily obtainable and can be
      used for the detection of antibodies in animals infected with A. pleuropneumoniae
      serotypes 7 and 4.

PMID- 9008805
TI  - In vitro infection of a cell line from Ictalurus nebulosus with Piscirickettsia
      salmonis.
AB  - Piscirickettsia salmonis, the etiologic agent of salmonid rickettsial septicemia
      (SRS), affects several species of salmonids. Previous reports using the
      appearance of cytopathic effect (CPE) as the criterion for susceptibility, showed
      that Piscirickettsia salmonis (ATCC strain) can be grown in vitro in some cells
      lines derived from salmonid fish, but not in BB cells from brown bullhead
      (Ictalurus nebulosus) and BF-2 cells from bluegill (Lepomis macrochirus). In this
      study we describe growth of P. salmonis (ATCC strain VR 1361) in a cell line
      previously believed to be nonpermissive for this organism. CPE was first detected
      in chinook salmon embryo (CHSE-214) and epithelioma papulosum ciprini (EPC) cell
      lines at 6 d postinfection (dpi). In contrast, using BB cell line, CPE was first
      detected 45 dpi and the monolayer completed CPE by 78 dpi. Electron microscopic
      examination of BB cells 78 dpi revealed free, intracytoplasmic and extracellular
      localization of the agent. P. salmonis was also observed within membrane-bounded
      vacuoles in BB cells, similar to that described in CHSE 214 cells. Contrary to
      earlier reports, results from the present study show that the BB cell line, is
      susceptible to Piscirickettsia salmonis infection. The delayed onset of CPE in BB
      cells in comparison to other permissive cell lines suggests that BB cells are not
      ideal hosts for P. salmonis. Interestingly, however, these results demonstrate
      that P. salmonis can infect non-salmonid cell lines, and raises the possibility
      that non-salmonid fish may play a role in the persistence and transmission of SRS
      in the natural environment.

PMID- 9008806
TI  - Differential reactivity of a monoclonal antibody directed to the membrane protein
      of porcine reproductive and respiratory syndrome virus.
AB  - A monoclonal antibody (2C12) against the 19 kDa membrane (M) protein of a
      Canadian isolate of porcine reproductive and respiratory syndrome (PRRS) virus
      was produced. By indirect immunofluorescence (IIF) cytoplasmic fluorescence was
      observed in infected cells, but the pattern of fluorescence was generally
      different and intensity was weaker than that observed using the nucleocapsid
      protein-directed monoclonal antibody SDOW17. When tested by IIF towards a total
      of 26 PRRS virus isolates from Canada, 122 isolates from the US and 13 isolates
      from Europe the 2C12 MAb reacted with all the North American isolates tested
      including the VR-2332 isolate and the vaccine (RespPRRS) isolate. However no
      reactivity was observed towards the European isolates tested including the
      Lelystad virus. This reactivity pattern suggests that the epitope recognized by
      this MAb on the M protein of PRRS virus appears highly conserved among North
      American isolates but absent or weakly expressed on European isolates of PRRS
      virus.

PMID- 9008808
TI  - A high efficiency technique for the long-term preservation of infective nematode
      larvae.
AB  - Improvements are suggested for the existing long term techniques for the
      preservation of nematode larvae. Haemonchus contortus, Teladorsagia circumcincta,
      Trichostrongylus colubriformis and Cooperia curticei larvae exsheathed in sodium
      hypochlorite and then suspended in phosphate buffered saline (PBS pH 7.2) are
      cooled in the gas over liquid nitrogen at a cooling rate of -1 degree C min-1
      down to -50 degrees C. Larvae are then stored in liquid nitrogen at -196 degrees
      C. After warming at 30 degrees C and reactivation at 20 degrees C for at least 12
      h, their percent motility is maintained (approximately 85%) providing that no
      more than 3000 to 5000 larvae are suspended in 1.8 mL of PBS in cryotubes.
      Infectivity does not significantly decrease: 46% of larvae cooled for 2 or 6 mo
      develop to adult stages compared to 52% for larvae stored at 4 degrees C for 2
      mo.

PMID- 9008807
TI  - Genetic and amino acid analysis of the GL protein of Canadian, American and
      European equine arteritis virus isolates.
AB  - The genetic variation in equine arteritis virus (EAV) GL protein encoding gene
      was investigated. Nucleic and deduced amino acid sequences from 7 different EAV
      isolates, including 4 eastern Canadian field isolates, were compared with those
      of the Bucyrus reference strain. Nucleotide sequence identities between these
      isolates and the Bucyrus reference strain ranged from 87.5% (Vienna isolate) to
      93.9% (11958 isolate). Amino acid identities with the Bucyrus reference strain
      varied from 90.2% (Vienna isolate) to 95.1% (19933 isolate). A 2nd potential N
      linked glycosylation site was found at position 81 in the GL protein of all EAV
      isolates. Three amino acid substitutions at residue position 90 (Glu-->Val),
      position 101 (Ala-->Val or Thr), and position 119 (Val-->Leu, Phe or Ser) were
      also found in all EAV isolates. Phylogenetic analysis showed that the North
      American EAV isolates, including the Canadian isolates, and the European
      prototype Vienna isolate could be classified in 2 distinct groups. Three putative
      sequential antigenic sites were predicted in EAV GL protein. The 1st antigenic
      site (TAQRFT) was located at positions 24 to 29, and the 2nd antigenic site
      (RYDEHTA) at positions 47 to 53. The 3rd antigenic site was predicted to be
      located at positions 78 to 84 and showed the less conserved amino acid sequence.

PMID- 9008809
TI  - Third ventriculostomy for hydrocephalus associated with spinal dysraphism:
      indications and contraindications.
AB  - Twenty-five patients have undergone this procedure at our unit. These constitute
      25% of our total experience with endoscopic third ventriculostomy (4). In the
      patients under 6 months of age, only one out of 11 patients has had a successful
      long-term result despite initial good fenestration of the floor of the third
      ventricle. These patients were selected on the basis of their adequate third
      ventricular size and a relatively slowly progressive hydrocephalus. Fourteen
      patients had a ventriculostomy performed instead of shunt revision. In 13
      patients this has been a success long term. All of these patients had a Heyer
      Schulte valve with antisiphon device installed for months, or more often, years,
      prior to the third ventriculestomy. We believe that the difference in these two
      groups is due to a very poor cerebrospinal fluid(CSF)-resorptive capability in
      patients immediately after back closure due to the prior venting of CSF into the
      amniotic sac. The absorptive capacity seems to improve with the passage of time
      in our patients who have had a shunt system that maintains a relatively normal
      intracranial pressure and thus contributes to the development of the patient's
      CSF-absorptive system.

PMID- 9008810
TI  - Plasma homocysteine and methionine concentrations in children with neural tube
      defects.
AB  - Mild to moderate homocysteinemia in women has been associated with an increased
      frequency of pregnancies with neural tube defects (NTD). Homocysteinemia is also
      an independent risk factor for premature vascular disease. In addition to folic
      acid, supplemental Vitamin B12, Vitamin B6 and betaine may normalize homocysteine
      metabolism, decrease the risk for NTD formation, and correct related metabolic
      imbalances in children with NTD. By means of automated amino acid analysis, we
      assessed total non-fasting homocysteine and methionine in plasma from 24 children
      with myelomeningocele. This study group (mean age 10.5 +/- 4.9 years) included 12
      girls and 12 boys randomly selected from our Birth Defects Clinic. Homocysteine
      concentrations in our patients (4.7 +/- 1.8 mumol/L) did not differ from those of
      20 randomly selected child controls (5.1 +/- 2.6 mumol/L). The mean homocysteine
      concentration for 36 adult controls (9.3 +/- 3.0 mumol/L) was significantly
      higher than the mean for either group of children (p < 0.0001). Linear regression
      analysis revealed negative correlation of total plasma homocysteine with serum
      folate (r = -0.53; p = 0.01), but not of homocysteine with either methionine or
      B12. Plasma methionine concentrations from our patients did not differ from adult
      reference values. Elevated homocysteine in some mothers of children with NTD has
      been attributed to defective methylation of homocysteine. These preliminary
      results do not indicate such a defect in the children themselves. A more
      comprehensive study of homocysteine, methionine and related metabolites in
      children with NTD and age-matched controls will be required to determine the
      clinical significance of these findings.

PMID- 9008812
TI  - The benefits of team treatment and control of adult patients with spinal
      dysraphism.
AB  - We investigated the outcome of newly referred patients to our spina bifida team
      in the period 1989-1994. 12 of 42 patients had spina bifida occulta, 8 had a
      meningocele and 22 a myelomeningocele. More than half of the patients underwent
      an operation which was beneficial to them. 13 operations for a tethered cord
      syndrome were performed with good results. In 15 patients referral delay caused
      unnecessary and mostly irreversible harm. Life-long regular control by members of
      a spina bifida team is, therefore, highly recommended.

PMID- 9008811
TI  - Occult spinal dysraphism--the common combination of lesions and the clinical
      manifestations in 50 patients.
AB  - Fifty patients (26 males, 24 females) aged from birth to 51 years with occult
      spinal dysraphism were identified. All had Magnetic Resonance (MR) scans carried
      out. The MR scans were examined to determine the vertebral level of the conus and
      to see if one or more of the following were present; lipoma, syrinx, dermoid,
      diastematomyelia, and meningocele. In 43 patients the conus lay below the level
      of L3, 23 had a lipoma, 23 a meningocele, 20 an open central canal in the spinal
      cord or a syrinx, 15 a diastematomyelia and 4 a dermoid. The commonest
      combination of lesions was a long cord, a syrinx or an open central canal in the
      spinal cord and a lipoma. The diastematomyelias were always associated with a
      long cord and had the highest incidence of vertebral body anomalies (60%). The
      most frequent recorded signs were deformities of the feet, short legs, wasting of
      the calf muscles, weakness of the legs, back pain and bladder dysfunction.
      Combinations of these occurred with all of the lesions although some had none.
      Whilst deterioration was seen in about half of the patients, acute deterioration
      was uncommon and was associated most frequently with a dermoid or an expanded
      syrinx.

PMID- 9008813
TI  - The cost of preventable conditions in adults with spina bifida.
AB  - Adults with spina bifida are at risk of developing secondary health conditions
      that are causally related to the primary condition and are to some degree
      preventable. By investigating preventable secondary conditions in adults with
      spina bifida, we can determine the burden of care that might be reduced if
      preventive strategies were developed. We audited hospitalizations of adults with
      spina bifida to gain insight into serious secondary conditions in this
      population. We reviewed all admissions of adults with spina bifida to a large
      American tertiary care center (Johns Hopkins Hospital; Baltimore, Maryland) over
      11 years. We determined the discharge diagnoses for each admission and the
      hospital costs associated with admission. We defined preventable secondary
      conditions in this adult population and calculated the percentage of total
      admissions and of total costs for these secondary conditions. The patient
      population consisted of spina bifida patients 18 years and over admitted from
      January 1982 to December 1992, including 59 females and 39 males. 77 of our
      patients were identified as white, 20 as black, and 1 as "other". Patient age
      ranged from 18 to 61 years with an average age of 25.8 years. There were 353
      admissions and admissions per patient ranged from 1 to 25 over the 11-year
      period. The average number of admissions per patient was 3.6 and the average
      length of stay for all admissions was 11.2 days. Of the 353 total admissions, 166
      (47.0%) were due to potentially preventable secondary conditions such as serious
      urologic infections, renal calculi, pressure ulcers, and osteomyelitis. For
      admissions due to these secondary conditions, the average length of stay was 12.5
      days. The total hospital costs, excluding professional fees, were $175,885,
      $247,355, and $437,262 for 1990, 1991, and 1992 respectively. Permanent loss of
      function resulting from secondary conditions, not investigated in this study, can
      also be a source of long-term financial and psychological cost to the patient.
      This study found a high number of patients with multiple admissions and that many
      admissions qualified as potentially preventable. More information is needed if we
      are to understand the factors associated with secondary health conditions in
      adults with spina bifida. We need to investigate the roles played by physician
      and patient knowledge, attitudes, and behaviors in contributing to patient
      outcome.

PMID- 9008814
TI  - Continuous (6 hour) urodynamic monitoring in children with neuropathic bladder.
AB  - In adults the development of modern equipment for ambulatory monitoring permits
      long-term evaluation of the lower urinary tract which is more accurate than
      standard urodynamics (SUD). In children continuous urodynamic monitoring (CUM)
      has been used infrequently and therefore standardisation of the method has not
      been previously achieved, nor have the techniques and difficulties of performing
      24-hour monitoring been solved. The aim of this study was to identify a technical
      method of CUM in children which was feasible and to verify its usefulness. For
      this purpose, we reviewed our preliminary experiences of CUM in children with
      neuropathic bladder. From March to November 1995 we made an outpatient study of
      the neuropathic bladders of 11 myelodysplastic children aged 1 to 18 years
      (average age 10.2 years). 7 of them were males and 4 females. All underwent SUD.
      With the children resting in bed, a 6-hour CUM (Lectromed MPR-2) was performed
      using a 4 Fr. microtip intravesical catheter (suprapubic in 3 infants and
      transurethral in 8 children) and an intrarectal catheter. The parents and/or a
      nurse monitored the fluid intake and micturition events and recorded the data in
      a diary. Based on the CUM experience in infants with non-neurogenic bladder
      dysfunction, the 3 suprapubic studies were done after 12 hours of urethral
      drainage in order to prevent leakage of urine. In all of the patients we were
      able to study 2 to 4 bladder fillings during a period of 6 to 8 hours (average
      6.5 hours) observation. In 9 of the 11 children the CUM pattern was comparable to
      the SUD one but in the 2 remaining patients CUM showed uninhibited contractions.
      Higher uninhibited voiding contraction pressures were recorded in hyper-reflexic
      bladders. Our preliminary results show that it is feasible to perform CUM in
      children and that it has advantages over standard cystometry in the investigation
      of children with neuropathic bladder even if it is carried out for short term (6
      hours).

PMID- 9008815
TI  - Long-term urological follow-up of occult spinal dysraphism in children.
AB  - From 1980 to 1996 we followed up 65 children with occult spinal dysraphism (OSD)
      out of 85 observed in our urodynamic laboratory. The average age at diagnosis was
      4.7 years (range: 1-21 years). In 19 cases (22%) the OSD was associated with
      anorectal anomalies (ARA). Urinary incontinence or voiding anomalies with urinary
      tract infection were the presenting symptom in 34 children (49%). At diagnosis
      all children underwent complete neuro-urological and urodynamic evaluation.
      Thirty-eight patients underwent neurosurgical correction. Vesicoureteral reflux
      (VUR) was present or developed in 17 patients: 15 underwent endoscopic procedures
      and 2 required surgery; 2 needed bladder augmentation because of upper tract and
      renal function deterioration. Urinary incontinence was treated mainly by
      intermittent catheterization and anticholinergic drugs, but endoscopic treatment
      was performed in 3 children. At long-term follow-up (2 to 14 years), socially
      acceptable continence was achieved in 78% of 57 children (8 could not be assessed
      because they were less than 4 years old). Upper urinary tract deterioration
      occurred in 15% and renal failure in 7.5%.

PMID- 9008816
TI  - Schizencephaly: surgical features and new molecular genetic results.
AB  - Schizencephaly is a rare developmental disorder characterized by a full thickness
      cleft within the cerebral hemispheres. Large portions of the cerebral hemispheres
      may be missing and are replaced by cerebrospinal fluid (CSF). The walls of the
      clefts are lined by polymicrogyric grey matter and are covered by the so-called
      "pialependymal seam". The cleft may be unilateral or bilateral, and if bilateral
      are fairly symmetrical. Their dimensions can be small or large. The clinical
      features may vary from a normal to a severe development delay. 13 patients with
      this anomaly have been evaluated. Using SSCP (single strand conformation
      polymorphism) analysis, as previously described (2), they were found to have a
      mutant homeobox gene, Emx2.

PMID- 9008817
TI  - Detrusorectomy with Mitrofanoff stoma.
AB  - The clinical and social benefits derived from bladder augmentation are well
      known. Most procedures involve the implantation of gastric or intestinal segments
      into the bladder. These have problems of the acid-haematuria syndrome, mucous
      production, urinary infection, stone formation and metabolic disturbances. Lang
      and colleagues presented their experiences in 1994 with detrusorectomy alone as
      an alternative procedure. We have performed detrusorectomy with Mitrofanoff stoma
      on 9 patients, protecting the denuded bladder mucosa with omentum. This
      represents 50% of the bladder reconstructions managed over an 18-month period.
      Follow-up urodynamics studies have demonstrated a compliant low-pressure system
      of good capacity in all but one case. Apart from this failure, all the rest are
      continent. One boy suffered a ruptured bladder due to rough play and another
      suffered excruciating bladder pain on drainage. He was managed by the
      instillation of bupivicaine (4 mg/kg) twice daily. Successful management of cases
      depends on intensive support of the outreach nursing service.

PMID- 9008819
TI  - The role of genetics in understanding hydrocephalus and spina bifida. An update.

PMID- 9008818
TI  - Treatment of defecation disorders by colonic enemas in children with spina
      bifida.
AB  - Faecal incontinence and constipation are well known problems in children with
      spina bifida. Effective treatment can be difficult and this gave the condition a
      low priority despite the obvious physical and psychological sequelae. Positive
      experience with colonic enemas (CE) in the paediatric post-operative care have
      led us to adopt this method as the treatment of choice for defecation disorders
      in children with spina bifida. In 41 spina bifida children (mean age 8.4 years,
      range 7 months to 22 years), retrograde CEs with hand-warm tap water were given
      at home from once a day to twice per week. Satisfaction with the procedure was
      evaluated with a questionnaire sent out after a mean follow-up period of 33
      months (range 6 to 55 months). The indications to start CEs were faecal
      incontinence (27%), constipation (27%) or both. 34% of 41 children also had other
      gastrointestinal complaints, 7% had headaches, 29% had poor appetite and 15% felt
      generally unwell. Before the start of CE 22% of the children had been on a diet,
      37% on oral laxatives, 31% on a rectal laxative and 44% had to have manual
      evacuations. 90% used diapers on a daily basis. At the end of the follow-up
      period 27% of the children were still on a diet and 17% still used oral laxatives
      but rectal laxatives were no longer used nor were manual evacuations necessary.
      66% of the 41 children were completely faecally continent and constipation
      occurred only occasionally, no child had faecal retention or impaction. At follow
      up 39% still used diapers regularly and 20% used a panty-line and complaints of
      abdominal pain, headache and poor appetite were rare. Satisfaction with the
      procedure was rated highly by 63% of parents and children and good by 37% but 15%
      of the children found regular CEs painful. It is concluded from the study that
      CEs are therapeutically effective in the treatment of both faecal incontinence
      and constipation in children with spina bifida. The procedure is well tolerated
      even by very young children. Long-term histopathological effects of daily CEs on
      the lower gastrointestinal tract needs to be evaluated by future research.

PMID- 9008820
TI  - Next steps: the Oregon Spina Bifida Project: community based services for
      children with chronic health conditions.

PMID- 9008821
TI  - Spatial learning and visual discrimination tests in hydrocephalic rat pups
      performed using the Morris water maze.

PMID- 9008822
TI  - Preliminary investigation of the performance of normal hydrocephalic and treated
      hydrocephalic HTx and Lewis rats in an 8-arm radial maze.

PMID- 9008823
TI  - Schizophrenia like syndrome following chronic hydrocephalus in a teenager.

PMID- 9008824
TI  - Bacterial infections in patients with cephalocele epidemiological data and
      therapy.

PMID- 9008825
TI  - Cognitive dysfunction in patients with congenital hydrocephalus and spina bifida:
      evidence for a dysexecutive syndrome?

PMID- 9008826
TI  - Increased intracranial pressure perinatally predicts early puberty in girls with
      myelomeningocele.

PMID- 9008827
TI  - Effects of GnRH analogues in the treatment of precocious puberty in children with
      myelomeningocele--preliminary results.

PMID- 9008828
TI  - Prolonged recording of intravesical pressure (vesical "Holter") in the child with
      spina bifida.

PMID- 9008829
TI  - Multidisciplinary management of caudal regression syndrome (26 cases).

PMID- 9008830
TI  - Sexuality disability and abuse. Research into practice?

PMID- 9008831
TI  - Sterigmatocystin: incidence, fate and production by Aspergillus versicolor in Ras
      cheese.
AB  - The occurrence, distribution, and stability of sterigmatocystin (STG) in Ras
      cheese were investigated. An incidence value for STG in market samples of Ras
      cheese was 35% with a mean value of 22.2 micrograms/kg. In experimental Ras
      cheese from milk contaminated with STG, 80% of the toxin was retained in the curd
      while 20% was found in the whey. The temperature for cheese ripening affected the
      toxin content. At 6 degrees C the toxin concentration was hardly affected, but at
      20 degrees C the concentration was reduced by 16% after 90 days. In Ras cheese
      contaminated with spores of Aspergillus versicolor, toxin production started
      after 45 days of the ripening, reached a maximum after 90 days, and declined
      thereafter. Cow's milk favoured toxin formation in comparison with buffalo's
      milk. Aged cheese (more than 6 months) inhibited toxin production.

PMID- 9008832
TI  - Effect of high fat diets with and without cholesterol on erythrocyte and tissue
      fatty acids in rats.
AB  - Male weanling wistar rats were fed synthetic diets containing 20% safflower oil
      (SFO) or palm oil (PO) with and without cholesterol for a period of six weeks.
      Erythrocyte membranes were isolated and their fatty acid composition were
      determined at the end of the experiment. Besides the fatty acid composition of
      the kidney and spleen lipids were also determined. Erythrocyte membrane, kidney
      fatty acids of rats fed safflower oil (SFO) had in the majority of variants a
      higher level of n-6 fatty acids when compared to palm oil group. However, in the
      spleen, the level of n-6 fatty acids in the palm oil groups were higher than in
      the safflower oil group. In general the arachidonic acid [20:4 (n-6)] levels were
      higher in the spleen and erythrocytes particularly in the cholesterol fed groups
      when compared to the kidney levels. Palm oil fed rats had a higher level of
      palmitic (16:0) and oleic [18:1 (n-9)] acids. Rats fed diets containing
      cholesterol significantly reduced the level of stearic (18:0) but increased the
      level of oleic [18:1 (n-9)], linoleic [18:2 (n-3)], and arachidonic acids [20:4
      (n-6)]. The ratios such as 18:1 (n-9)/18:2 (n-6), 18:1 (n-9)/18:0, 18:2 (n
      6)/20:4 (n-6) and 20:4 (n-6)/18:2 (n-6) are all indicative of the normal activity
      of enzymes involved in the desaturation and elongation. Thus these studies
      indicate that addition of cholesterol can modify the fatty acid composition in
      erythrocytes, kidney and spleen lipids.

PMID- 9008833
TI  - Magnesium, calcium and phosphorus contents in daily food rations in primary
      school children: questionnaire and analytic studies.
AB  - Aims of the performed studies included working out a technique of determining
      representative rations on the basis of questionnaire studies on school children
      in Wielkopolska west region of Poland. The reconstructed representative daily
      food rations provided grounds for analytic studies. The studies were performed in
      the four seasons of the year. The studied food rations failed to cover the
      recommended daily intake of Mg and Ca. On the other hand, the daily intake of P
      transgressed the food norms. The inadequate Ca to Mg and Ca to P ratios were
      interpreted as deserving special concern when confronted with the market
      situation in Poland and as creating particular health hazards for the studied
      school children. The employed statistical analysis demonstrated that the
      suggested technique of determining representative rations may be employed in
      evaluation of Mg, Ca and P intake.

PMID- 9008834
TI  - Farm-grown mushrooms (Agaricus campestris) in the diet of rats do not affect
      plasma and liver cholesterol concentrations.

PMID- 9008835
TI  - Development, acceptability and nutritional evaluation of home made supplements
      for school children.

PMID- 9008836
TI  - Signal transduction molecules in the rat pineal organ: Ca2+, pCREB, and ICER.
AB  - The mammalian pineal organ transduces light-dependent neural inputs into a
      hormonal output. This photoneuroendocrine transduction results in a largely
      elevated concentration of the pineal hormone melatonin at night. The rhythm in
      melatonin production and secretion depends on activation and inactivation of
      transcriptional, translational, and posttranslational mechanisms fundamentally
      linked to two second messenger systems, the cAMP- and the Ca(2+)-signal
      transduction pathways. Here we review molecular biological, immunocytochemical,
      and single-cell imaging studies, which demonstrate a time- and substance-specific
      activation of these signaling pathways in rat pinealocytes. The data provide a
      framework for understanding the complex interactions between second messengers
      (cAMP, Ca2+), transcription factors (CREB, ICER), and their role in regulation of
      melatonin synthesis. The data have proven the rat pinealocyte to be an
      interesting model to study transmembrane signaling pathways which may be common
      to both neuroendocrine and neuronal cells.

PMID- 9008837
TI  - How do proteins acquire their three-dimensional structure and stability?
AB  - Proteins are multifunctional in the sense that their specific amino acid sequence
      simultaneously determines self-organization, function and turnover.
      Correspondingly, evolution has to compromise between rigidity (stability) and
      flexibility (function/degradation) to the effect that the free energy of
      stabilization of proteins is the equivalent of only a few weak interactions
      (delta Gstab = 45 +/- 15 kJ.mol-1). Molecular adaptation of thermophiles,
      psychrophiles and other extremophiles is accomplished by extrinsic factors that
      are not encoded in the amino acid sequence, or by minute local structural changes
      involving mainly ion pairs and hydrophobic side chains. The acquisition of the
      native three-dimensional structure may be described by single- or multiple
      pathway folding and association, where the fast collapse of the polypeptide chain
      leads to molten-globule-like states; subsequent shuffling reactions yield
      structured monomers which, in the case of oligomers, undergo specific association
      to form the native functional state. The rate-limiting steps (cysteine oxidation,
      proline isomerization, subunit assembly) are catalyzed or directed by enzymes or
      chaperones.